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An Acid-Base Approach
by Michael Smith
O N O O
H OH2 Ka = [NO3–] [H3O+] [HNO3] [H2O]
O N O O H3O+
Nitric acid is a stronger acid than water, so water is the base and nitric acid is the acid in this reaction to generate the nitrate anion (conjugate base) and the hydronium ion (conjugate acid).
H H O NH3 Ka = [HO–] NH4+] [H2O] [NH3] H O H-NH3
Water is a stronger acid than ammonia, so ammonia is the base and water is the acid in this reaction. The reaction products are hydroxide anion (conjugate base) and the ammonium ion (conjugate acid).
Br H Br NH3 Ka = [Br–] [NH4+] H-NH3
[HBr] [NH3] (c) Hydrobromic acid is a stronger acid than ammonia, so ammonia is the base and HBr is the acid in this reaction to generate the bromide anion (conjugate base) and the ammonium ion (conjugate acid).
Cl H OH2 Ka = Cl–] [H3O+] Cl H3O+
[HCl] [H2O] (d) Hydrochloric acid is a stronger acid than water, so water is the base and HCl is the acid in this reaction to generate the chloride anion (conjugate base) and the hydronium ion (conjugate acid). Cl Cl NH3 Cl C Cl C H Cl NH2 Cl Na
[CCl3–] [NH3] [HCCl3] NaNH2]
The amide anion is clearly a base, which makes the proton of chloroform a stronger acid, so NH2 – is the base and chloroform is the acid in this reaction to generate the –CCl3 anion (conjugate base) and ammonia, NH3, as the conjugate acid. 27. The main reason is likely the relative size of the bromide ion (182 pm) versus the chloride ion (100 pm). Greater charge dispersal for the bromide ion leads to greater stability of that conjugate base, and a larger Ka.
[H3O+] [Cl–] [H3O+] [Cl–]
[HCl] H2O [HCl] 28. In this reaction, water is the base that reacts with the HCl. If water is omitted, the base has been excluded from the equilibrium constant expression for an acid-base reaction.
29. (a) NH3
NH3 F3B 30. The ate complex in the “box” is the reaction product, where N of ammonia is the electron donor (the base).
31. Oxygen is more electronegative than nitrogen, so nitrogen is more electron rich, and will be a better electron donor. In addition, the ate complex from ammonia is an ammonium salt whereas water will react to form an oxonium salt. The ammonium salt is more stable, which contributes to the overall increased Lewis basicity of the nitrogen atom in ammonia. 32. In these neutral molecules, phosphorus is larger than nitrogen, with covalent radii of 106 pm and 71 pm, respectively. The charge density of nitrogen is greater. Therefore, ammonia is expected to be the stronger Lewis base. 33. An ate complex is the salt generated by reaction of a Lewis acid with a Lewis base. The atom derived from the Lewis base expands its valence and assumes a positive charge, whereas the atom derived from the Lewis base expand its valence and assumes a negative charge.
H3C O H3C Cl Al Cl Cl
35. The C-H bond is much stronger than the N-H bond, so it is more difficult to break. Nitrogen is larger and better able to accommodate charge relative to carbon, so H3C– is significantly less stable (more reactive) than H2N–. If the –NH2 conjugate base is more stable, Ka is larger, and ammonia is a stronger acid.
36. (a) CH3OH is the strongest acid in this series. The O-H bond is more polarized and easier to break, and the methoxide anion, H3CO–, is more stable than the anions from CH4 or CH3NH2. NaF does not have an acidic proton, and it is not a Brønsted-Lowry acid. (b) As explained in section 2.4 of the text, the size of the conjugate base increases from fluoride towards iodide, so the iodide in is more stable. This means that Ka is larger for HI and decreases going towards HF. Since iodide is much larger, the H-I bond is longer, and weaker, s it is easier to break relative to the others. 37. The iodide in is much larger, and the charge is dispersed over a greater area. Therefore, it is more difficult for iodide to donate electrons to an acid relative to fluoride. In other words, iodide is a weaker base.
O N O H BASE H-BASE O N O
O 38. O As shown, nitric acid generates the resonance stabilized nitrate anion. In the nitrate anion, the charge is dispersed over several atoms, which makes it more difficult for that species to donate electrons to an acid. For hydroxide ion, HO–, the charge is concentrated on the oxygen atom, and it is much easier to donate electrons. The charge is not dispersed as in the nitrate anion, and hydroxide is more basic.
39. The fluoride is much more stable relative to the methide anion, H3C: –, which means that carbon will donate electron more easily. The methide anion is the stronger base. 40. Determine the pKa for each of the following. (a) Ka = 1.45x105 (b) Ka = 3.6x10–12 (c) Ka = 6.7x10–31 (d) Ka = 18 (e) Ka = 3.8x1014 pKa = –log10 Ka. (a) 5.16 (b) 11.44 (c) 30.17 (d) –1.26 (e) –14.6 41. The more acidic acid will have the smaller pKa. Of this series, HCl is the strongest acid (pKa –7) relative to HF (pKa 3.17). Water has a pKa of 15.7 and ammonia has a pKa of about 25. Clearly, HCl has the smallest pKa. 42. The least acidic acid will have the largest pKa. Of this series, HCl is the strongest acid (pKa –7) relative to HF (pKa 3.17). Water has a pKa of 15.7 and ammonia has a pKa of about 25. Clearly, ammonia is the least acidic and has the largest pKa. 43. NaF is an ionic salt, Na+ and F–. The electron rich fluoride ion is the only atom of these two that can donate electrons, so F is the basic atom. 44. As described in section 2.4, HI is a stronger acid, as is evident from the smaller pKa for HI, because of the weaker HI bond and the larger size of the iodide ion (the conjugate base), which leads to charge dispersal that makes that conjugate base less reactive.
H H H 45. The reaction of A gives the conjugate base shown, and B gives the conjugate base indicated. In both cases, the charge is dispersed over three atoms (resonance). The OH bond is weaker than the NH bond, and that proton is easier to remove. Oxygen holds onto electron better than nitrogen (it is more electronegative), so the conjugate base from A is less likely to donate electrons (it is more stable, which shifts the equilibrium towards the conjugate base). Although it is not obvious from the diagram, the charge dispersal is more efficient in the conjugate base from A. All of these combine to make A much more acidic (pKa of 4.8 versus 46).
O + HOH O
H H + NaOH
H O O 46. H (a) The conjugate base derived from formic acid is resonance stabilized by charge dispersal over several atoms, as shown. The conjugate base from methanol has the charge concentrated on oxygen, and no charge dispersal is possible. (b) If there is a larger concentration of the conjugate base, the equilibrium is shifted towards the right (towards the conjugate base), and Ka is larger. (c) If Ka for formic acid is much larger, it will be the stronger acid, and will react better with NaOH.
H + HOH
He is 1s2 Be is 1s22s2 Mg is 1s22s22p63s2 23. Al is 1s22s22p63s23p1 Cl is 1s22s22p63s23p5 Br is 1s22s22p63s23p63d104s24p5 Ti is 1s22s22p63s23p63d24s2 Cu is 1s22s22p63s23p63d104s1
24. 25. Both are Group 1 elements. Potassium is a larger atom, which means that the 4s1 electron is held less tightly than the 3s1 electron on sodium. Using a very simple rationale, it should be easier to lose the electron from potassium, and the resulting K ion is larger than the Na+ ion, and will be more stable. 26. No single orbital may hold more than two electrons, and if there is more than one orbital of the same energy (degenerate orbitals), no one orbital may hold two electrons until all orbitals hold one. For the 2nd row, there is one s orbital and three degenerate p orbitals. Therefore, adding one electron to the 2s orbital gives Li and adding the second to that orbital gives Be. Adding one electron to a 2p orbitals gives B, and the 2nd electron goes to a different 2p orbital to give C, and the third fills the last 2p orbitals to give N. the next electron will spin pair in a 2p orbital to give O and the net electron will spin pair to give F. 27. A spherical 4s orbital penetrates closer to the nucleus than a 3d orbital, so it is screened less from the nuclear charge and gains extra stability by being filled preferentially to 3d. In addition, adding an electron to the 3d shell requires that the 9 electrons reconfigure, whereas adding the electron to the 4d shell completes the spherical symmetry.
Br (a) Br C
Br (b) CH3 Br CH2
O C CH2 CH3 (c) CH3 C N (d)
Cl Br C
The sp3 hybridized carbon atoms are indicated by the arrows.
H (a) CH3 ionic ONa+ (b) Br (c) CH3C C-H covalent CH2 (h) C covalent (i) (d) CH3C C-Li ionic (e) KCl ionic
C H H covalent O
(H°C-N + H°H-I) H° = (50 + 104. Cl-CH3 (C-Cl = 84 kcal/mole) Iodine is larger than Br.(H°C-C + H°I-I) H° = 2x50 . H H H propane H C C H H C H H H C H H H H C C H H H C H H butane .392 eV) has the highest ionization potential. H H N C H C H C H H HH C H H C C H H H H H H H° = H°products .341 eV). 33.5) = 100 .3) = 154. H Cl Cl H C H H (e) (b) H C H H C H (f) Cl O H H H C (c) H O C H H H C H Cl Cl (a) Cl C H H (d) 31. (d) H° = (H°C-I + H°N-H) .6) .139 eV).9 .4 + 257.4 + 257.3 + 80.(104.181.H°reactants 32.5 kcal mol-1. I-CH3 (C-I = 56 kcal/mole). and the least reactive of the three.344.7 = –173.(87.5 kcal mol-1.2) .(145 + 36. which correlates with the weaker C-I bond and the stronger C-Cl bond.(H°H-Br + H°C-O) H° = (67 + 104. The C-I bond distance is the greatest.7 kcal mol-1.7 = –190.2 .2 + 145) = 337. it is more difficult to lose an electron and it will be less reactive than Na (5. K is more reactive than Na.344.(H°O-H + H°C-C) (257. so it is expected to be the most reactive.3) = 171. 34. which is larger than Cl. Since Li (5. which is more reactive than Li.2 .(87.2 = 88. The numbers indicate that it requires less energy to remove an electron from K (4.5 = –81. (c) (H°C-O + H°C-H) . Br-CH3 (C-Br = 70 kcal/mole). and the C-Cl is least. (b) H° = 2xH°C-I .249. Therefore.30. (a) H° = (H°C-Br + H°H-O) .2) .5 kcal mol-1.
s orbital p orbital hybrid orbital d orbital 40. Dipole moment = 0 H (f) Cl C Cl Cl 37. After loss of one electron. (a) C N polarized covalent C F polarized covalent (b) N O polarized covalent (e) C C (c) C H nonpolarized covalent (f) Li C polarized covalent (d) 36. 41. the lowest energy reaction adds one electron to give the Noble gas electronic configuration. the electronic configuration of the ion F+ is 1s22s22p5 39. which is more stable. Cl (a) H C H H (b) nonpolarized covalent H O C H H Cl (c) Cl C Cl H CH3 (d) H3C C CH3 (e) H CH3 no polarized bonds. Dipole moment = 0 Cl C H Br Cl 4 polarized bonds. Iodine is much larger than fluorine. and leads to the lowest energy reaction pathway. so the C-I bond distance is greater than that of C-F. 38. Based on this simple analysis. but they all cancel. and loss of one electron to form Li+. with the Nobel gas configuration.(a) (f) C Li N C (b) (g) N C O F (c) (h) N C H H (d) (i) Cl H Br Cl (e) B C 35. the C-I bond should be weaker than the C-F bond because there is less electron density per unit distance between the nucleic. Lithium has one electron in the outmost shell. In reactions with halogens. which is quite stable. . in Group 17.
C-O and C-F. leading to a polarized covalent bond. Loss of one electron generates the ion Na+. 44. and no difference in electronegativity of the bonded atoms. which is unlikely. similar to that formed for a C-C bond. so the electronic configuration is 1s22s22p6. The C-O bond will be a sp3 hybrid orbital in a -covalent bond. It will have the familiar hybrid orbital shape: 47. if it can form at all. The C-C bond is the least polarized because there is no heteroatom. . 45. Sodium (Na) has the electronic configuration 1s22s22p63s1. Three covalent bonds attached to a central atom will form a trigonal planar geometry.42. 46. In C-N. Mixing a 1s and a 2p orbital is expected to generate a higher energy molecular orbital. one atom is more polarized than the other. There is greater difference in energy between 1s and 2p orbitals than between 2s and 2p. A 2p orbital has a dumb-bell shape: 43. Carbocation Cl3C+ has three covalent bonds and the positively charged carbon is characterized by a p-orbital that does not contain electrons. and the positive carbon will have sp2 hybridization.
and G have the same empirical formula. . D. (a) Structures A. (a) -CH3 -CH2CH2CH2CH3 -C H CH3 CH3 CH3 -C C CH3 H H2 3C = propyl C100H202 -CH2CH3 -CH2CH2CH3 3C = propyl (b) C5H10 C6H14 C5H8 C5 = pent C60H120 (c) C5 = pent 26. (A) CH2 CH2 CH2 CH3 CH2 CH2 CH2 C8H18 CH2CH3 (B) H3C CH2 CH CH3 CH2 CH2 C8H18 (C) CH3 CH2 CH2 CH H3C CH2 CH2 CH3 C8H18 CH2 CH2 CH3 H3C CH3 H3C CH3 (D) CH2 CH CH2 (E) H3C C CH2 CH3 H3C CH2 CH2 CH3 CH2 CH2 CH2 C8H18 C9H20 CH3 CH CH2 (F) CH2 CH (G) 2 H3C C CH3 H3C CH3 CH3 CH CH2 CH2 CH2 CH3 C8H18 C10H22 (b) The isomers with the formula C6H14 are marked. C. B. and are isomers. longest chain = 4 butane CH2 H3C CH2 CH3 longest chain = 4 butane CH2 H3C CH CH3 CH3 tridecane longest chain = 3 propane H3C CH CH3 CH3 H3C longest chain = 5 pentane CH2 CH2 CH3 CH CH3 25.CHAPTER 4 butane decane 24.
7-trimethylundecane CH CH2 CH2 CH2 CH3 6-propylpentadecane 29.isomers C6H12 C6H14 C6H14 C8H18 C6H14 27. CH2CH3 (a) CH2 H3C CH2 CH2 CH2 octane CH2 CH2 CH3 (b) H3C CH2 CH2CH3 CH CH2 CH CH2 CH2 CH2 CH2CH3 CH2 3. Note: cyclic alkanes have the formula CnH2n. 28. so C5H10 and C60H120 may be cyclic alkanes.7-diethyldecane CH2 (d) CH2 H3C CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3 (c) H3C H3C C CH2 CH3 CH2 CH2 CH2 CH2CH2CH2CH3 CH CH3 CH2 3. . so only C5H12 and C100H202 are acyclic alkanes.3. An acyclic alkane must have the general formula CnH2n+2.
.6-dimethylheptane 220.127.116.11-tetramethylpentane 2.3-dimethylheptane will have the formula C9H20.2.3. but there are others.(a) (b) 1.3-trimethylhexane 18.104.22.168-tetramethylcyclohexane 3.4-trimethylhexane 2.3. 2. (a) Isomers of 3.3. Several are shown.4-tetramethylpentane (b) Isomers of 1-bromooctane will have the formula C8H17Br.4-dimethylheptane 2. Several are shown. but there are others.9-dimethyl-8-(2.2-dimethylpropyl)nonadecane Br (c) octane (d) 5-bromo-5-ethyl-8-methyldecane 30.
but there are others. (a) 3. cyclohexane methylcyclopentane 1-ethylcyclobutane 1.3. C7H16 C7H14 C7H14 C7H16 . C9H20 C9H18 C9H20 C8H18 (b) Isomers of 2-methylhexane will have the formula C7H16.4-trimethylpentane 3-bromo-2.3-Diethylpentane has a formula C7H16. assume they are cyclic alkanes. so there are NO isomers.1.3-dimethyl-4-bromo-hexane 2-bromo-2. None of these alkanes have that formula.4.3-trimethylcyclopropane 31.2-dimethylcyclobutane 1.4-trimethylpentane (c) With a formula C6H14. Several are shown.Br Br 2-bromo-6-methylheptane Br 3-bromo-4-methylmethylheptane Br 2-bromo-2-3-dimethylhexane Br Br 3.
4.4.2-dichlorobutyl)-2-methylhexadecane Cl Cl (c) 1-chloro-2. C7H16 C7H14 C7H14 C7H16 (d) Isomers of cyclohexane will have the formula C6H12.4-hexamethylheptane (g) 5-(1-methylpropyl)decane .3-triethylcycloheptane (b) 5-(1. C6H12 C5H10 C6H12 C8H16 C6H14 32.2.1-diethylcyclohexane Br Br (h) 2.2.(c) Isomers of cycloheptane will have the formula C7H14.2.3. (a) 1.4-di(1-methylethyl)cyclohexane Cl (e) 2.2-dibromo-3-methyloctane (f) 1.4-tetramethylhexane (d) 1.3.
so 85.5134g and g H = 0.7692 g of water and 1.0855 Assume a hydrocarbon.5989 x 100 = 85.28/7. 1-cyclohexyldodecane ethylcyclohexane (a) CH3CH2CH2CH2CH2CH3 (b) (CH3)2CHCH2CH2CH3 (c) CH3CH2CH2CH2CH2CH=CH2 37. use pent-. (d) CH3CH2C C(CH2)8CH3 .28 so.81% %H = 0.81/12 = 7.6000 g was burned in the presence of oxygen to give 0. g C = 0.15 and moles H = 14. In cyclohexyldodecane. the long chain has more carbon atoms than the ring.0855/0.15= 2H / C = CH2 = any cylic alkane formula CnH2n 34.28 g H.8827 = 0. moles C = 85.33. so the base name is dodecane. A sample weighing 0.2727 x 1. For a 5-carbon chain. so the base name is cyclohexane.5989 x 100 = 14.5134/(0. CH3 -CH3 -CH2CH3 -CH2CH2CH2CH3 HC CH3 -CH2CH2CH3 C CH3 CH3 CH3 35. so %C = 0.28% Assume 100 g. the substituent chain has fewer carbon atoms than the ring.7692 = 0.0855) = 0. 36.5134/0.1111 x 0.5134 + 0. 14. In ethylcyclohexane.8827 g of CO2.81g C and 14.28/1 = 14.
x5 = C5H8. g C = 0. This fits the genreal formula for alkanes: CnH2n+2.2727 x 2.71% %H = 0.7147/(0. 11. so C4H10.6208 = 0.7147/0.0743) = 0. (c) A sample weighing 1.35= 1. and matches the CnH2n-2 formula.6 x 2 = C2H3.2116= 0. so %C = 0.5 x 2 = C2H5 .8758/(0. so 84.6344 = 0.14 and moles H = 14.6688= 0.04 x 100 = 84.71/12 = 7.4779 = 0. C5H8.0743 Assume a hydrocarbon.1642 Assume a hydrocarbon.0953 Assume a hydrocarbon.7147g and g H = 0.8758g and g H = 0.7147 + 0.21% %H = 0.23% %H = 0.21/12 = 7.1111 x 1.02= 12.0953/0.6208 g of CO2.4457/(0.79 g H.6344 g of CO2.21 g C and 15.77 g H. g C = 0. The last one makes sense. So.0953) = 0.35 and moles H = 11.79/1 = 15. so %C = 0.04 x 100 = 15.23g C and 11.4779 g of water and 3. so %C = 0.79% Assume 100 g. moles C = 85.25H / C = CH2.2727 x 1. .81 x 100 = 11. moles C = 84.5200 x 100 = 85. g C = 0.4.77/7.77/1 = 11. moles C = 88. so 88.4457/0.29 so.29/1 = 14.2727 x 3.8758/1. (a) A sample weighing 0.4457 + 0.4457g and g H = 0.23/12 = 7.52 x 100 = 14. x3 = C3H4. so 85.38.1111 x 0.8758 + 0. etc.1642) = 0. 15. x4 = C4H6.79 so.8578 g of water and 2.29% Assume 100 g.81g was burned in the presence of oxygen to give 0.1642/1.79/7.8578 = 0.6H / C = CH1.8100 x 100 = 88.1111 x 0.14= 2H / C = CH2 = any cylic alkane formula CnH2n (b) A sample weighing 0.29/7.04 g was burned in the presence of oxygen to give 1.71g C and 14.6688 g of water and 1.02 and moles H = 15.29 g H. 14.2116 g of CO2.52g was burned in the presence of oxygen to give 0.2 .77 so. Calculate the % C and H as well as an empirical formula for each of the following using the combustion analysis provided.8.0743/0..77% Assume 100 g.
4-dichloro-2. 39. but that does not fit one of the general formulas.4-dichloro-6-ethyl-7.5-triethylcyclohexane F (e) F F (f) nonane (g) H C H H fluoromethane Cl Br Cl (j) 5-(3.1122/0.(d) A sample weighing 0.3.2727 x 0. so C4H8.12 g was burned in the presence of oxygen to give 0. so %C = 0.1.31% Assume 100 g.17H / C = CH2.69 g C and 15.06 and moles H = 15.935g and g H = 0.2-diethylpropyl)tridecane 4.3-tetramethylcyclooctane F 1.69% %H = 0. 15. 4.4 .31/1 = 15.4114= 0.06= 2.3-difluorobutane)-4.7 This is close to the genreal formula for alkanes: CnH2n+2.7-di(1.4114 g of CO2. Try C10H22.1122(0. Noe: C6H13 is obtained.2-dimethyl-5-(2.17 x 2 = C2H4.2-dimethylcyclohexane (d) 1.3. g C = 0.8.1122 + 0. so keep going.0702 = 0.31 so.0184) = 0.31 g H.6-dimethylheptane (a) (b) Cl Cl (c) 1.69/12 = 7.31/7. so 84.0184/0.12 x 100 = 15.1656 g of water and 0.1111 x 0. moles C =84.1dimethylethyl)tridecane .12 x 100 = 84. C10H21.4-diethyl-6-fluorotridecane (h) (i) 2-bromo-4-ethyl-3-methylheptane 6-ethyl-2.0184 Assume a hydrocarbon.
octane. C and I are identical. A B C D G E F H I . 2. Cl (a) (b) (c) Br 1-bromo-3-chlorocyclohexane Cl 6-ethyl-3.3-dimethylhexane. A and F and G are identical.4.1. The four different structures of A-I are isomers of each other.40. 3.5dimethylhexane.2-triethylcycloheptane 7-(1. 42. all with the formula C8H18. D and H are identical.10-diethyl-2-methyltetradecane (a) tert-butyl (b) isopropyl (c) isobutyl (d) sec-butyl (e) (f) tert-amyl amyl 41. B and E are identical. 3-ethylhexane.22.214.171.124-tetramethylpentane 1.4-timethylnonane 3-chloro-6-ethyl-2-methylnonane I (d) (e) (f) 3-iodo-2.2-trimethylbutyl)-6.
chlorine is much larger than hydrogen. as well as the three unshared electron pairs on each chlorine atom. the Cl-C-Cl bond angle is larger (111.3-dimethylheptane 4-ethyl-2-methylhexane Cl Cl Cl F Br Br Cl Cl (b) 2.6-dimethylheptane 3.43.3-dimethylheptane 2-ethylheptane 2. (c) 2. For this reason. .4-dibromooctane 45. nonane 3-methyloctane 4-methyloctane 2-methyloctane 2. As seen in the models.5-trichlorodecane 44.47°).2-dichloro-4. and the size of the chlorine atoms.6-dimethyl-3-fluoroheptane (a) 3. leads to repulsion that pushes the chlorine atoms apart.3.4-dimethylheptane 2.15°) relative to the H-C-H bond angle (109.
(d) CH3CH2C C(CH2)8CH3 55.CHAPTER 5 52. The same is true for (f). (f) Li (g) CH2 . C=O or C=Cl structure. (b) alkane. All valences are satisfied. (e) alkyne. where the nitrogen is present as ammonium. •• H •• H H CH3 CH3 CH3 (a) C N C (b) N O F (c) (h) C N H H (d) (i) Cl H Br Cl (e) B C 56. Structures (a). (a) (a) alkene or cyclic alkane. and the adjacent carbon is sp3 hybridized. Cation (e) cannot form a C=C unit to the adjacent sp3-hybridized carbon. H3C (a) CH3 N C CH3 H (c) H H •• O C H (d) H •• Cl C H (b) H O C H H3C (e) H C C H (f) CH3 H3C H N C H H Structure (b) is an oxonium ion. (d) alkane. H Br Br O 2 sp3 C sp (b) CH CH2 (c) 2 H C CH3 C N sp (d) Cl Br C (a) Br 3 sp Br CH2CH3 C sp3 (e) CH=CH2 CH2 sp2 CH2 CH CH3 CH3 H (f) C CH CH H sp2 C Osp3 CH2 C H 2 H sp H C16H34 C10H20 (d) (e) C9H16 (f) C100H200 (b) C20H42 (c) C8H14 53. and there is not possibility of a C=O structure. respectively. which has all valences satisfied. (c) alkyne. (c) and (d) have resonance forms that involve a C=N. (f) alkene or cyclic alkane (a) CH3CH2CH2CH2CH2CH3 (b) (CH3)2CHCH2CH2CH3 (c) CH3CH2CH2CH2CH2CH=CH2 54.
H3C CH3 N (H3C)2HC H3CH2C °° °° N CH(CH3)2 CH2CH3 H (a) NH2 (b) N (c) H3C N CH3 CH3 60. If you make a model of both structures. H H dipole is zero 59. Cl (a) H C H H nonpolarized covalent H (b) H C H O H (c) Cl Cl C Cl Cl H H H C H (d) H H C H C H H C C H (e) Cl dipole is zero H C H Br (f) Cl H C Cl Cl 58.they are different. so there is essentially a 50:50 mixture of both (see chapter 9). they rapidly interconvert by fluxional inversion.(a) C N polarized covalent C F polarized covalent (b) N O polarized covalent (e) C C (c) C H nonpolarized covalent (f) Li C polarized covalent (d) 57. you cannot superimpose them . (a) OCH3 O OH (b) O . However. Counting the electron pair. OH OH 61. there are four different groups on N.
OH OH OH (c) 4C 2° alcohol 3C 1° alcohol 6C 3° alcohol (d) Is it possible to draw a two-carbon secondary alcohol? No! At least three carbon atoms are required. A three-carbon tertiary alcohol? No! At least four carbon atoms are required. . highest (a) (i) (b) lowest NH2 OH (ii) CO2H highest (ii) CH3NH2 (ii) CH3 lowest highest OH (i) OH (e) CH3 (ii) OCH2CH3 (ii) NH2 (b) hydrogen-bonding OH (d) O hydrogen-bonding OH (e) O hydrogen-bonding (f) London London lowest OH OH (iii) OH (i) lowest (c) CH3Cl (i) OH (d) (iii) CH3COOH highest (iii) CH3 OH (iii) CH2CH2CH2OH highest (iii) O (c) dipole-dipole 62. (i) lowest (a) 63.
OH O partly soluble (b) (a) (c) soluble insoluble OH OH NH2 (d) OH OH soluble (e) O OH O insoluble (f) insoluble . Resonance delocalization leads to the resonance contributors shown. O O O O O OH O O base A O O B O O 66. O O O (a) CH3O(b) O– (c) CH2(d) O O O– 65.64. the electrons on the negatively charged oxygen atom can be delocalized into the adjacent -bonds. Note that these are estimates based on the “8-carbon rule per functional group”. In other words. and tropolone is considered to be a “vinylogous” carboxylic acid. and are not necessarily correct based on experimental evidence. as in B. much like the carboxylate anion seen in carboxylic acids. and the charge can be delocalized to the second oxygen. the p-bond is directly connected to the negatively charged atom. Reaction with a base generates alkoxide anion A. It is possible to view B and A as a “carboxylate anion” because of the delocalization that is made possible by the intervening -bonds. In both (b) and (d). This extension of reactivity by intervening -bonds is known as vinylogy. leading to the resonance structures shown. Therefore. the OH proton of tropolone is acidic in large part because the resulting conjugate base is resonance stabilized in a way that allows the carbonyl group to be involved.
because those terms will not be discussed until chapter 9. C and D and F are isomers C7H16O C7H16O OH O A HO E C8H18O F OH C8H16O B O G C8H16O C8H16O O H O O C O D O O I C6H14O2 C6H16O2 HO H C8H16O2 68. A and B are isomers.4. Note: The E/Z nomenclature for certain alkenes is omitted.67.8-dimethyl-1. 6-(1-methylpropyl)oct-5-en-1-yne (CH2)4CH3 (a) (b) (c) (d) 4.1-dimethylpropyl)-1-decene .4.5.6-nonadiyne (g) (e) (f) (h) 3-ethyl-5-methyl-1-hexyne 7-methyl-6-(126.96.36.199-tetramethl-3-octene 4-ethyl-4-methyl-1-octene (CH2)4CH3 6-methyl-7-(1.2-dimethylpropyl)-6-tridecene 2.5-pentamethyl-2-hexene 5-ethyl-4.
1-dimethylethyl)cyclohexene 188.8.131.52-pentadecadiene (d) 1.69.8-di(1.3-diphenylcyclotridecene Ph Ph (f) (g) Ph 1-2-propynylcyclodecane 4-fluoro-4-phenylcyclononene (h) (i) F cycloheptadecyne .should be used with (e).184.108.40.206-dimethylcycloheptane I (a) (b) (c) (d) 1.6-pentamethylcyclohexene Br (e) Br 3. 1-ethenyl-6-iodo-2.3.3-diethylcyclopropene 4-(1. (a) 5-(2. but this nomenclature will not be discussed until chapter 9. Note: The term trans. leaving out the trans term is OK.5. Therefore.7-tetraethyl-2-dodecyne (c) 7.5.6-hexamethylcyclohexene (e) 1-cyclopropyl-2-ethylcycloheptene (f) 5.4-dibromocyclopentene 13-(1-methylethyl)-1.6. for this problem.2-dimethylbutyl)-2-hexadecene (b) 4.5-diethyl-3-nonyne 70.1-dimethylethyl)-1.
3-decadiene .4. There are many answers for this question.4-trimethyl-2-pentene 5-ethyl-2.1-difluoro-3.6-dimethyl-1-nonene Br (e) C (f) (g) C Br 4-(bromomethyl)-1.1-dimethylpropyl)-2.2-dimethyl-3-propylcyclopentane 1. 6-ethyl-4.5-trimethyl-1-octene 3-chloro-4-ethyl-3-octene (a) Ph Cl (b) (c) F F (d) CH2CH3 5-ethyl-5-phenyl-3-octene 1. 1-ethyl-2-methylcycloheptane methylcyclononane cyclodecane 1.4-trimethyl1-heptene 72. Only 10 rather typical structures are provided. so it is omitted here.5.71.2-hexadiene 7-bromo-2-methyl-6-(1.1-dimethylcyclooctane 1-decene 5.7-dimethyl-3-octene 6-methyl-2-nonene 5-methyl-4-nonene 2. Note: N/Z nomenclature is not introduced until chapter 9.3.
10-dimethyl-6-dodecanol . E/Z Nomenclature is not discussed until chapter 9.4-triethyl-2-propylhex-5-yne-1-ene Et 5.4-dimethyl-1.3-dimethyl-1. so it omitted here.8-nonadiene 5-butyl-4-hexyl-2.5.6-diphenyl-3-heptene Cl Cl (l) Cl (m) (CH2)4CH3 3-methyl-6-phenyl-3-propyl-1-hexyne 4-(3-methylbutyl)-4-ethyl-5-iodo-2-octyne Et Ph (n) (o) C C-CH3 I 3.3.4-dimethyl-3-phenyl-3-pentanol OH Ph (a) (b) Cl (c) HO Ph (d) Cl 3-phenyl-3-hexene 2-chlorocyclopentanol 4-ethylcyclohexanol OH (f) (g) HO 2-chloro-3-methyl-2-hexene (e) CH2(CH2)8CH3 (h) CH2CH3 4-methyl-3-heptene 4-ethyl-3-methyl-3-tetradecene 7.8-methyl-7-(1.4-diphenyl-1-hexyne CH2CH2CH3 (p) Ph (q) C C-H (CH2)4CH3 Ph Ph (r) (CH2)4CH3 4-(1-phenylbutyl)-3.6-heptadiyne 3-ethyl-5.6-trimethyl-5.4-diethyl-1-nonyne (k) 3.5-dimethyl-4.3-pentadiene 3-ethyl-5-phenyl-1.5.5-trichloro-2.3-dimethylhept-6-yn-2-ene 73. 2.2-dimethylpropyl)-6-tridecene Ph (h) Ph (i) (CH2)4CH3 (j) Ph 3.
3-hexanediol Ph OH (n) Br 3-methyl-3-heptene F (o) (p) Cl OH C C-H 4.4. OH (a) 2-methyl-1-cycloheptanol (b) 5.6-hexamethylcyclohexanol OH (h) 3-chloronon-8-en-1-ol OH OH Ph Cl 75.2. .6-diphenyl-2-heptanol Ph (d) 5-(3-ethylhexyl)-8-chloro-1-pentadecanol OH Ph OH (c) hex-2-en-1-ol OH OH (e) 3.5.5-dibromo-4-octene (m) 3-hexene 4-phenyl-hex-3-en-2-ol hept-6-yn-2-ol 4-chloro-3-fluoro-3-heptene 74.4-cyclopropyl-2-methyl-2-pentanol OH Br (i) (j) OH (k) (l) OH 2.5-heptanetriol OH (g) 4-phenyl-220.127.116.11-octanediol OH Cl OH (f) 1.
4-dichloro-2.H (b) N N-butylpiperidine NHPh CH3 (e) (f) Cl N Cl N-methylcyclohexylamine (c) N CH3 (a) N N.6.5-trimethyloctanal H formal (formaldehyde) H 4-phenylbutanal O 2-methyl-3-hexanone (d) 3-methyl-4-phenyl-2-pentanone (e) 6-bromo-5.5-dimethyl-3-heptanone 1-ethylcyclohexane carboxaldehyde Cl (h) Cl CHO (i) O .6-trimethylheptanamine H 1-chloro-1chloromethylmethanamine or di(chloromethyl)amine 76.3.N-di(1-methylethyl)butanamine Ph (d) H2N 2-phenylpentanamine N-phenyl-2. O (a) (b) 2-ethylhexanal O CHO (c) Ph 2-methylcyclobutanone O Br (f) CHO (g) O dicyclohexylmethanone (dicyclohexyl ketone) O (j) H 4.
and all of the carbon atoms of the bonds are directly connected (no intervening sp3 -hybridized atoms). so it planar. (c) and (e) have sp3-hybridized atoms in between the C=C units. and it is a ring.5-dimethylhexanedioic acid (d) 3-chlorocyclohexane-1-carboxylic acid CO2H HO2C CO2H Cl (e) 2. A -bond is formed by the direct overlap of two hybrid orbitals. it is a weaker bond.see chapter 21). and all of the electron density of the bond is concentrated on a line between the two carbon nuclei. Benzene is a molecule that has 3 -bonds confined to a ring. and (f) has 3 -bonds connected. A -bond is formed by sideways overlap of two adjacent and parallel p-orbitals. In a -bond. only some of the electron density is shared. Both (a) and (d) have -bonds confined to a ring.6. Draw the structure of the following molecules. with the same type of resonance stability (called aromaticity . Compounds (b).77. If the shred electron density is less in a -bond. so they cannot experience the same type of resonance.3. (a) (b) (c) (d) (e) (f) 79. with no intervening sp3-hybridized atoms.6-tetrabromohexadecanoic acid Br Br Br CO2H Ph CO2H Br (c) 2. This latter statement will be explained in more detail in chapter 21. (a) 8-phenyloctanoic acid (b) 3. . so resonance delocalization is possible.5-dimethylcyclopentane-1-carboxaldehyde CHO 78. but they are not confined to a ring.
83. also making the sulfonic acid more acidic. 82. (a) Both products are shown. The four C-F bonds in tetrafluoromethane cancel. so it is more stable. and butane only has non-polarized C-H bonds. methanesulfonic acid O H H H C S O H H H H C O methanol O H H H H C O H H H C O S O O H H C H O S O O H H C H O S O O . so the charge is localized on the oxygen atom. Methane and ethylene are hydrocarbons with no polarized bonds. and non-polar. so the molecule is non-polar. 81. In other words. The methoxide anions derived from methanol is not resonance stabilized. the charge density on oxygen in methoxide is much grater than the charge density on oxygen in the methanesulfonate anion. Fluoromethane (CH3F) has a single polarized bond and is the more polar molecule. sulfur is a large atom relative to carbon. In addition.it is a weaker base. but do not have a polarized X-H bond. Methanesulfonic acid gives the methanesulfonate anion and acetic acid gives the acetate anion. and there is less electron density available for donation . Propanoic acid (3rd choice from the left) is the only molecule capable of hydrogen bonding. (b) Both conjugate bases are resonance stabilized. as shown. since it has the polarized O-H unit. This increased stability for the conjugate base should shift Ka towards products. and readily available for donation . The methanesulfonate anion is resonance stabilized.it is more basic. but there are more resonance contributors for the methanesulfonate anion. and this will contribute to increase charge dispersal. so the charge is dispersed over several atoms. making the sulfonic acid more acidic.methanesulfonic acid O H H H C S O H H H C O O C O H H H H H H C O C C O S O O H H C H H O H C O S O O C O O H H C H O S O O H H H acetic acid 80. The ether and the ketone are capable of dipole-dipole interactions.
5(2)-6 = 0 FC = 6-0.5.5(6)-2 = 0 FC = 6-0. All are straight-chain alkanes. Infrared data is from Table 14.5(8)-0 = +1 . and hexane has the greatest mass.5(4)-4 = 0 H C • • • •O H FC = 6-0.pairs all Cl's have 3 e Spectroscopy Problems (to be done only after chapter 14 has been read and understood) 87.5(8)-0 = 0 Cl Cl .(a) H2C sp2 sp C NH sp2 (b) H H H C C N •• 84.pairs FC = 7-0. Hexane will have the highest boiling point. FC = 5-0. 86.5(2)-6 = -1 (e) FC = 4-0. NMR data is from Table 14. 85. •• (d) C C H H C •• O H H •• O FC = 6-0.5(6)-2 = +1 H O (a) H C C H H H H (b) H C H H N H C H Cl (c) H H C H N C FC = 5-0.5(8)-0 = +1 •• •• FC = 4-0.5(6)-2 = -1 3 e.5(2)-6 = 0 Cl C Cl H C C H H H N H H •• FC = 4-0.3.5(2)-6 = -1 •• •• FC = 5-0.5(8)-0 = 0 Cl (f) Cl C FC = 7-0.
about 2817 cm–1 C=O. about 3300 cm–1 C N.O (a) C=O. about 2220 cm–1 C C-H. about 2500-3000 cm–1 C=O. about 1725 cm–1 (b) OH OH. about 1725 cm–1 C C. about 3300 cm–1 12 10 8 6 PPM 4 2 0 10 8 6 PPM 4 2 0 Me (e) HO C N OH. one peak at about 3400 cm–1 4 3 2 PPM 1 04 3 2 PPM 1 0 . about 2240–1 (f) N H primary NH. about 1730 cm–1 aldehyde CH. about 3300 cm–1 3 2 PPM 1 04 3 2 PPM O H 1 0 (d) (c) CO2H OH.
66 x 10–7 (b) pKa = -3.35x10-6 : pKa = 5.0 (f) 0.26 x 10–11 CH2 O OH H NH2 H H3C H3C CH2 O H3C C O C O + H-O-H H3C CH2 C O O CH2 C O O + H-NH2 H3C H3C H3C H3C C O H OH CH3 C O NH2 H H3C O C H3C CH3 H3C H3C C O + H-O-H + H-NH2 CH3 N C N C C N C N C N C C N C O H3C S O O H3C S O O H NH2 O H OH OH H CH3 N C N C C N C N C N C C N C O H3C S O O H3C S O O + H-NH2 O + H-O-H + H-O-H H NH2 + H-NH2 41.12 x 10–24 (d) pKa = 10.1 : Ka = 1.7 (d) Ka = 9.1 40.8 : Ka = 1.78 : Ka = 1.5x10-12 : pKa = 10.01 x 10–11 (e) pKa = 35.2x10-3 : pKa = 2.58 x 10–3 (c) pKa = 23.04 (e) Ka = 10.CHAPTER 6 39.1 (c) Ka = 18.2 : Ka = 1.08x10-3 : pKa = 4.583 x 10–36 (f) pKa = -11. .5 : Ka = 3.3 : Ka = 5. (a) pKa = 6. (a) Ka = 6.33x108 : pKa = –9.1x107 : pKa = –8.2 (b) Ka = 12.
(a) 3. Me Cl H Cl Me H O H B A O O H O 44. internal hydrogen bonding is possible in A.5-diethyloctanesulfonic acid (d) hex-4Z-enoic acid CO2H Check chapter 9 for the Z- SO3H 42. . the COOH group is close to the Cl. Internal hydrogen bonding will lead to enhanced acidity for A relative to B. In other words. As noted in A. H Cl H H HO Cl A CO2H O H O Cl CO2H O O H Cl H H Cl H O Cl O O B H H H 45. Acid (A) is slightly more acidic because the proton of the COOH unit is closer to the Cl. which is held in space due to the rigid nature of the molecule.3-diphenylbutanoic acid Ph Ph CO2H (b) 4-chloro-2-methylpentanoic acid Cl CO2H (c) 5. which allows better internal hydrogen bonding when compared to acid (B). but not in B. carboxylic acid A has a smaller pKa than carboxylic acid B. Therefore. 43.
For all practical purposes. (c) Water. so there is no reaction at all with propanol. so propanol will react as a base. which is a much stronger acid than propanol. (d) Ethanol. so propanol will likely react as a very weak base or a very weak acid. The conjugate acid is an oxonium ion. (e) NaNH2 . which is a much stronger acid than propanol. The conjugate acid is the hydronium ion. which is slightly more acidity than propanol. it is neutral. it is neutral. The conjugate acid is hydrogen sulfate ion. so proposal will likely react as an acid. which is a much stronger acid than propanol. (h) H2SO4. (b) HCl. and HCl is a much stronger acid than propanol.O O S O O (a) H3CH2C (b) O O O S O O H3CH2C O O O S O O CH2CH3 CH2CH3 (c) (d) O (e) NMe (f) no resonance O CH2CH3 O O Cl O O O Cl O O Cl O O Cl O O O O O O no resonance no resonance 46. it is neutral. so propanol will likely react as a very weak base or a very weak acid. which is a significantly weaker acid than propanol. so proposal will react as a base. so propanol will likely react as a weak acid. The conjugate acid is water. For all practical purposes. . (f) 2-Butanone. The conjugate acid is chloride ion. (a) NaOH. For all practical purposes. so propanol will likely react as a very weak base or a very weak acid. (g) Methane. Methane is not acidic or basic. so it is neutral. The conjugate acid is an oxonium ion. The conjugate acid is ammonia. and sulfuric acid is a much stronger acid than propanol.
in large part because the two COOH unit are on opposite sides of the rigid alkene unit. In fumaric acid (B). There is no rotation about the C=C unit. Maleic acid (A) with a pKa of about 1. 48.8 is more acidic because one carboxyl group is relatively close to the OH unit of a second carboxyl group (they are on the same side of the molecle). . the pKa is about 3 is higher (less acidic). so internal hydrogen bonding is possible.O O (a) –NH 2 O + H-NH2 O O (b) H –NH 2 H O + H-NH2 H O O O O O (c) O –NH 2 O O + H-NH2 (d) O H –NH 2 O O + H-NH2 O (e) O H –NH 2 O O + H-NH2 O 47.
Butanoic acid is a weaker acid than acetic acid. In 2bromopentanoic acid. The alkyl group is electron releasing relative to the carbon attached to the carbonyl. which is a much stronger base than diethyl ether. (f) CH3SO3H Cl3Fe H-NEt3 54. The real point of this question is to emphasize that an acid only reacts as an acid in the presence of a base. and that the strength of the acid depends on the strength of the base it reacts with. where the methyl group is electron releasing relative to H. and the amine and H:base are on the right. Therefore. 52. the Br is relatively close and internal hydrogen bonding is possible that leads to enhanced acidity. HCl is technically not a base under such conditions. Ka can be determined. the bromine atom is very far away from the polarized O-H unit. so propanoic acid is more acidic in diethylamine than it is in ethyl ether. (a) (b) (c) Cl-H F3B NEt3 NEt3 NEt3 Cl– F3B—NEt3 H-NEt3 H-NEt3 H-NEt3 CH3CH2COOH NEt3 NEt3 NEt3 CH3CH2COO– Cl3Al—NEt3 CH3SO3– Cl3Fe—NEt3 H-NEt3 H-NEt3 (d) Cl3Al (e) 53. Compare HCOOH with CH3COOH. Formic acid is a stronger acid than acetic acid for the same reason. Compare R-CH2COOH with CH3COOH. For the reverse reaction where the ammonium salt-base pair is on the left. In 5-bromopentanoic acid. Propanoic acid reacts much better with diethylamine. If there is no base. HCl cannot react as an acid. The reaction of the conjugate . O Br O O H Br O H 50. 51. where R is an ethyl group. It is possible to look at the reverse reaction of the conjugate acid derived from reaction of an amine with an acid (an ammonium salt).O O A O H O O H H O O B O H 49. This means that Ka for the reaction with diethylamine is larger and Ka for the reaction with diethyl ether is smaller. which diminishes the acidity by strengthening the O-H bond by inductive effects.
acid/conjugate base uses the term KBH. N N (a) triphenylphosphine Ph P Ph (c) ethylphenylphosphine H P Ph CH2CH3 Ph (b) butylphosphine H3CH2CH2CH2C P H (d) 1. The term KBH is used to evaluate the basicity of a base such as an amine. .2-(diphenylphosphino)ethane Ph Ph P Ph H H (c) CH3 H (f) H3C S (g) CH3 H (j) O (k) H3C H3C H H H N H O H (h) CH3 O OH O (d) H O H H H P Ph 56. which makes diisopropylamide a stronger base. as it is slightly more difficult for the base to approach the proton in diisopropylamine. Diisopropylamine is a weaker acid than diethylamine. Look at the amine precursors to the amide anions. (a) O (b) H O H H3C O (e) H H (i) N H 57. 55. and a larger value of KBH (small pKBH) indicates a weak base whereas a smaller value of KBH (large pKBH) indicates a stronger base. The reason is probably some steric hindrance of the isopropyl group relative to ethyl for removal of the proton from nitrogen.
61. whereas base strength increases to the right. and the ethyl group provides some steric hindrance when the oxygen atom approaches another molecule. Based on this trend. Note that nucleophilic strength across the second row increases to the left. CH3CH3–I CH3CH3–I CH3CH3–I CH3CH3–I CH3–I CH3–I CH3–I CH3–I –OMe –:C –OMe –:C CH3CH3–OMe CH3CH3–C C-Me CH3CH3–CN CH3CH3–I CH3–OMe CH3–C C-Me CH3–CN CH3–I CMe –CN –I CMe –CN –I 62. 59. The reaction of diethylamine with HCl gives Et2NH2+ as the conjugate acid. 60. and it is a much weaker nucleophile in its reaction with acetone than is the amide anion. The increased stability of the conjugate acid in ethanol shifts Ka towards the conjugate acid. which has one unshared electron pair. leading to increased stabilization of the conjugate acid. 63. The conjugate base of propyne is CH3C C:–Na+. The hydrogen bonding in diethyl ether is much less because there is no O-H bond. Therefore. This indicates that the alkyne anion is reasonably strong base. which is consistent with diethylamine as a stronger base in ethanol than in diethyl ether. the alkyne anion may react as a . Therefore. The amide anion (-NH2) has a much higher charge density (two unshared electron pairs) relative to the neutral molecule ammonia (NH3). making it the strongest nucleophile in this series.(a) O AlCl3 (b) O BF3 (c) N BEt3 BF3 (e) Cl FeBr3 (f) O ZnI2 (d) O 58. which is more electronegative than N. F is more electronegative than O. and the NH unit of the ammonium salt is capable of hydrogen bonding with the protic solvent ethanol. the electrons on nitrogen in –NH2 should be more available for donation. an ammonium salt. Ammonium salts are acidic. . ammonia is less able to donate electrons to a positive carbon. and the alkyne has a pKa of about 25.
H°C-I = 91 .2) .(H°H-O ) H° = (75) . but in order to attack the carbon atom as a nucleophile.7).(104) = 0.2 kcal mol-1. (c) H° = (H°C-O) . and the acid-base reaction is more facile and much faster. so G° = H. 15. the closer an electron withdrawing substituent such as chlorine to the sulfonic acid proton. Assume that S is zero. but it is somewhat removed from the sulfonic acid unit. By analogy with carboxylic acids. In simple terms. Sodium methoxide (NaOMe) can react with the slightly acidic proton of methanol in an acid-base reaction.base with water (pKa. 65. all of the bond dissociation energies will be the same in that an O-H bond is broken in the reactants.(H°C-H) H° = (104. SO3H hexanesulfonic acid SO3H 3-methylbutanesulfonic acid SO3H Cl 2-chlorobutanesulfonic acid . H° = H°products . which is consistent with a reversible process. If the same base is used. OH just “leave” (be displaced). There is probably very little different in pKa for the other two sulfonic acids. (a) HCOOH (formic acid) (b) CH3OH (methanol) (c) CH3SO3H (methanesulfonic acid) This is a very misleading question.2) = –29.H°reactants NH3 (a) CH3OH + Cl3CH + H2O (b) ICH3 (c) CH3ONa + (a) H° = (H°N-H) .(104. (b) H° = (H°H-O) . The methyl group probably exerts a small effect. the more acidic . 2-chlorobutanesulfonic acid should be the most acidic. CH3O– + +NH4 Cl2C– +OH3 CH3OCH3 (ignore NaI) H CH3OH + CH3I H3C O CH3 I– 66. H° = H°products .2 = 0. Therefore. It is 67.2 kcal mol-1. 3-metylbutanesulfonic acid has an electron releasing methyl group.(56) = 35 kcal mol-1. It was given to make a point. whereas no such reaction is possible if the neutral solvent THF is used.56 = +35 kcal mol–1 This number indicates an endothermic reaction. G° and H° calculations cannot be used to determine differences in reactivity. important to state that this is not the only criterion for reversibility in a reaction.H°reactants H° = H°C-O .due to internal hydrogen bonding (through space inductive effects). 64. but this molecule is probably slightly less acidic than hexanesulfonic acid. hydroxide is a very poor leaving group in this reaction.(H°C-I) H° = (91) . 68. Therefore. Stability of the conjugate base is the usual criterion for determining differences in acidity for these three compounds.
There is no doubt that the oxygen of the ether is a much stronger base than the fluorine atom of fluoromethane: O is less electronegative than F. electronegativity and basicity decreases going down the periodic table. 70. BF3. O AlCl3 O AlCl3 F AlCl3 F AlCl3 .69. Remember that fluxional inversion about nitrogen occurs in both amines. the electron pair is partly delocalized on the adjacent carbonyl. section 3. In the amide. where the electron pair is reasonably available for donation. 71. and it is the stronger base. Trimethylarsine (Me3As) has the larger arsenic atom relative to nitrogen of trimethylamine. which exacerbates the steric hindrance in (Me3C)3N. The more hindered amine is (Me3C)3N. methanamine is the more basic. Therefore. AlCl3 reacts faster with diethyl ether. This means that trimethylamine will react faster with the Lewis acid. 73. but it is slightly less electronegative (see chapter 3. relative to methanamine. with the three bulky tert-butyl groups.7). In N-chloromethanamine (Cl-NHCH3). and the oxonium ion product is more stable than the CF-Al unit resulting from fluoromethane. it is a weaker base than the amine. making is less reactive and a weaker base. relative to the three relatively unhindered ethyl groups in (CH3CH2)3N. In general. O O H N H N O H O H O N H O H N H O O H 72. the electron withdrawing chlorine group should diminish the availability of the electron pair on nitrogen. so the electron density on nitrogen is more available. Therefore. or at least the electron withdrawing effects of the carbonyl diminish the availability of the electron pair for donation. Therefore. It is more difficult for the proton of formic acid to approach the nitrogen atom in (Me3C)3N.
5. The answer is similar to in question 77. infrared data is from Table 14. . so there will be no signal in the 33003500 cm–1 region. The OH unit in 2-propanol is capable of hydrogen bonding. 77. Me Me Spectroscopic Problems (to be done only after chapter 14 is read and understood) In all of the following. 75. The extent of internal hydrogen bonding is much greater for the acidic proton of a carboxylic acid. CO2H 2500-3000 cm–1 1730 cm–1 OH 3300 cm1 12 10 8 6 PPM 4 2 04 3 2 PPM 1 0 76. which effectively changes the O-H bond distance. the secondary amine N-methylaminoethane will have a singlet in that region. The OH unit in a carboxylic acid is capable of hydrogen bonding. As the amount of internal hydrogen bonding changes. Triethylamine has no hydrogen atoms attached to nitrogen. which in turn influences the amount of shielding. and far downfield. which greatly diminishes the amount of shielding. In other words.3. which in turn influences the amount of shielding. In the IR. that proton is very deshielded. The ammonium salt does have a N-H group. the tertiary amine trimethylamine will have no signals in the 3300-3500 cm–1 region. 78. which effectively changes the O-H bond distance. 79.Me H N HgCl2 Me H N HgCl2 74. the chemical shift of the proton changes. NMR data is from Table 14. and the primary amine 1aminopropane will have a doublet (2 peaks) in that region. and will therefore show a bond in that region.
N N H 3 2 PPM 1 04 3 2 PPM 1 0 NH2 6 4 PPM 2 0 80. O HO H H O H 10 8 6 PPM 4 2 0 10 8 6 PPM 4 2 0 .
CHAPTER 7 HO NaCN O NaNH2 NaI Ph NaCN Ph I NaNH2 Ph NaI OH NaCN O NaNH2 H NaI O H essentially no reaction H (a) HI I HBr (b) Br CN NH2 HO O poor yield essentially no reaction CN Ph NH2 I CN H OH NH2 poor yield 20. (c) HCl Cl 21. .
so G° = 56 kcal mol–1 + 373. H CH3I + CH3OH (a) H3C O H (b) (c) CH3CH3 + CH3NH2 F-F + (CH3)3C-CH3 N CH3F H H + (CH3)3C-F CH3 Me3CH + I – Me3C-F (d) H° = H°products . (b) H° = (H°C-N) .0032/56) x 100 = 0.0032 = x.(H°C-H) H° = (109) . The point of this exercise is to begin the process of learning those reactions are reasonable and those that are unlikely. The temperature cannot be lowered below absolute zero. No! Energy equal to the activation energy must be added to initiate the reaction. The transition state is that portion of the energy curve that represents the point at which bonds begin to break in the reaction and begin to form in the product.6) = +28.H°reactants (a) H° = (H°C-O) . .0032 = –20.19 = 54.6 kcal mol-1.(H°C-I) H° = (257. and this has nothing to do with whether or not the overall reaction is endothermic or exothermic.625 24.0057%.(37.15 x 0.4 kcal mol-1. H° = H°products .2 cal–1. The calculation suggest that the temperature must be lowered for –20. which is obviously impossible. (d) H° = (H°C-F) .(H°C-H) H° = (184) . Remember that temperature must be converted to Kelvin. To calculate the temperature for G° = –10: G° = -10 = 56 +x (0.0032 kcal mol–1 = 56 .3) .8 kcal mol–1 The S° term is (0. It is not possible to “see” it.(H°F-F + H°C-C) H° = (109 + 109) .4 = +35.(80. G° = H° + T S°.H°reactants All of these hypothetic reactions are endothermic as written. 26.625 Kelvin. G° = H° + T S°.6) = +103. 23. A transition state is not a detectable or isolable entity.4 + 145) = 218 . and H° = 56 kcal mol–1.4 kcal mol-1. The difference in energy between the energy of the reactants and the energy of the transition state is the activation energy.22. which is 0 K.1.0032) (–10 –56 )/0.(50) = +207. T = 100°C. but rather a point on an energy surface. 25.182.(80. (c) H° = (H°C-F + H°C-F) . so x = –66/0. and S° = 3.3 kcal mol-1. Br Br transition state 27.
73x10–6 . Based on the plot.009 sec. so the proton of acetonitrile is relatively acidic.24 -1.693 0.00031 .B:----------H-------CH2CN H-CH2CN B: B:H + –CH2CN 28. k.00028 AoB ABo/AoB .5 ln(ABo/AoB) 0 .40 0. Plot ln [A] versus time in seconds.8 27.12 .095 .971 1. The half life is k/0.64 .00048 .3 53.00042 . the slope is 0. The slope of the line is the first order rate constant.693.23 0.270 . second order half life = 1/k[Ao].0 191.00023 1.12 Time (sec) 0 25 50 100 150 200 250 300 350 400 30.00038 .00036 1.00029 1.47 -1.405 -0.728 .253 time(sec) 0 17.00048 1 . This carbanion is resonance stabilized. so the rate constant k = 0.693 = 0.29 0.00011 2.07 . first order half life = k/0.36 -0.19 0.10 .693.00029 .0 1. using the best straight line possible.8 240.6 151. ABo .5 0.00039 1.52 .52 0.66 -2. the second order rate constant is 0.006.65 -0. where for second order reactions. given the following data.1 86.006.0051.00035 .113 .00008 3.006/0.2x10-6: half life = 1.31 . Based on the plot of the data.7 0.00043 . assume [A]o = 0. (a) a first order reaction where k = 1.92 -1.419 . H H C C N: C C N: H H 29. Calculate the half life.95 0.12 ln[A] 0. [A] 2. Half-life = k/ln 2 = 0.05 -0.5.00015 2.1 31. and relatively easy to remove if a strong base is used (see chapter 22).
6x10-9: (f) a second order reaction where k = 3. Assume that S° is zero. and how many hours would be required for the reaction to go to at least 98% completion. In the case of reaction B. the equilibrium constant suggests there is more product than reactant. K = 1.303 RT (log K) and the reaction temperature is 25°C (298.45x10-3 log 10.7) = 9166.7) = -0.23x1018 = 118.77x10-9 = -8.37x10–3 (c) a first order reaction where k = 5.7.09 x -1363.7 = –7923 (b) 1. and e = 2.15 K).718 (base of natural logarithms).7) = 33.81 x -1363.25x10-4: half life = 2162 half life = 8.66x10–10 (e) a first order reaction where k = 0.024 K = 0.40. and e = 2. K = 1.303RT) = ( G° /-1363.303 = -1363.7) = -0.55x10–6 = -5.44 3: half life = 8.718 (base of natural logarithms). The answer to this question depends on how easy it will be to separate reactions and products..15 = 592.986x298. the equilibrium constant is close to 1.15 K).986 cal/deg mole.3 kcal mol–1 ( G° /-1363.986 cal/deg mole.7 = 10991 (d) 4.7) ( G° /-1363. but the yield of product will be higher from reaction A. RT for all reactions = 1.7 = –7691 (e) 1. (10 pts) The half-life for a certain reaction is 8 hours. If K = 10-( G° /-1363. G° = -RT (ln K) = -2.986x298.13 x -2.7 = 15846 (c) 8.06 x -1363.03.7) = 0. R = 1. Estimate how many half-lives.7 = –161039 (f) 10.5 kcal mol–1 (b) 100. R = 1. H—I I– I 36. T = temperature in Kelvin.7) K = 10-( G° /-1363.0 K = 1x10-33 –1 (d) 18. 35. If it is relatively easy to separate these compounds. For reaction A.303 RT (log K) and the reaction temperature is 25°C (298.03 (e) -33 kcal mol–1 ( G° /-1363.074 K = 1.303 = -1363.44x1012: half life = 5. RT for all reactions = 1.7 (a) 2.5x10 ( G° /-1363. so we anticipate the ability to isolate the product.2 K = 0 34.8x10 (d) a second order reaction where k = 9.5 = 0.1x10-3 K = 0. T = temperature in Kelvin.5: half life = 0.014 K = 1.64 x -1363.7 = 2700 33. G° = -RT (ln K) = -2.(b) a second order reaction where k = 4. .7) = 1.98 x -1363.4x105 log 4.83x10–13 32.5 kcal mol ( G° /-1363. so there will be close to a 1:1 mixture of reactants and products.55x10-6 log 1.398 x -1363.45x10-3 = -1.4x105 = 5. so G° = H° in all cases.7) then for reaction A.946 (f) -12. so ( G° /-2.13 x -2.5x106 kcal ( G° /-1363.23x1018 log 1.997 (a) -1.15 = 592. then product can be isolated from both A and B. and for reaction B.5 log 2.18 4 cal mol–1 (c) -4.77x10-9 log 8.
5.003 sec. generating the more stable tertiary carbocation B from the less stable carbocation A. then the final product must arise by the reaction of bromide ion with carbocation B. The only way to obtain the final product is for a skeletal rearrangement to occur. 39. which means that it proceeds by one electron transfer as shown. one must conclude there is no intermediate. (a) (b) (c) I I (CH3)3C CH3–Cl CH3 Cl CH3–I I–CH3 (CH3)3C–Cl Cl . Therefore. so D is likely to be the major product of this reaction.29 sec.2-H shift (a rearrangement) 38 There is no indication that a transient product appears and is then consumed as in Figure 7. 1/360 = 0. Br H–Br H—Br Br– A B 1. 40. whereas reaction (b) is a radical process.37. Based on this calculation. formation of D is faster than formation of C. The methyl group in CH3O– is electron releasing relative to the H in HO–. the reaction of HBr and the alkene reactant must give carbocation A. from A to B. For the two competing reactions.2-hydride shift. Reactions (a) and (c) are two electron transfer reactions. Which of the following is likely to be the best two electron donor in a reaction with CH3Cl? Explain. both reactions are second order. This rearrangement occurs by transfer of a hydrogen atom from A to B. and for reaction B. the electron density on O in methoxide anion is grater. chloride ion should be the poorest electron donor (weakest nucleophile). Based on electronegativity. and it should be the best electron donor (strongest nucleophile). Based only on this curve. Therefore. and the starting concentration is assumed to be 1. 1/3. the half life = 1/k. However. If there are carbocation intermediates. and larger size of the ion (which means more charge dispersal). 41. This rearrangement is referred to as a 1.5 = 0. For reaction A.
which does not have axial or equatorial substituents.4-dimethyltetrahydrofuran N Ph O 41. The molecule circled has no axial substituents. The last structure on the left is a boat conformation. but the “flagpole” chlorine atoms are close in space. .CHAPTER 8 40. then the molecule with the fewest axial substituents will have the least transannular interactions. Cl Cl Cl H Cl H H H Cl H ecipsed-syn H H H H Cl H Cl eclipsed HH H H H Cl H staggered-anti staggered-gauche 42.3-dimethyloxirane (b) N. and the substituents are not as far away as possible (the anti conformation).3-diethylpyrrolidine (c) 4-hydroxypiperidine HO N NH O (d) 3-chlorooxetane Cl O (d) N-phenyl-2-methylaziridine (e) trans-3. only equatorial. (a) cis-2. Assuming that each chair conformation is locked. Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl 43. and this constitutes significant transannular strain. The circled structure has the most axial bromine atoms. A gauche conformation is a staggered conformation in which the two substituents (Cl) do not eclipse any other atom. whereas all of the others have several axial substituents.
. It is a staggered conformation with the two Cl atoms as far apart as possible (180°). In the gauche conformation. intermolecular hydrogen bonding with the solvent should stabilize the anti conformation more than the gauche. The circled molecule fits that description.H H Br ax BrH H H H Br Br H H Br ax H H H H Br H H H H H Br H ax Br H H H H Br ax H H H H Br ax H H H Br H H H H H H BrH 44. internal hydrogen bonding is possible in an aprotic solvent. but methanol is a protic solvent. H Cl H H staggered-anti H Cl H Cl H H Cl H Cl staggered-gauche Cl H H H H H H H H Cl Cl staggered-gauche eclipsed-syn H H Cl • H H Cl H H Cl Cl H H H H H H Cl Cl 46. Therefore. It is reasonable to assume that the molecule with the most cyclopropane rings will have the greatest Baeyer strain. 47. Cyclopropane is a flat molecule with significant Baeyer strain. The anti conformation is marked. 45. but what may be less obvious. introducing even more Baeyer strain. is that attaching four cyclopropane units to the fourmembered ring will flatten the four-membered ring.
524Å (152. and is the lowest energy conformation. The boat conformations with the two chlorine atoms in flagpole positions has the highest transannular strain. staggered-gauche eclipsed-syn eclipsed 50. The large chlorine atoms are in close proximity. Br H Br H H H Br H H H Br H staggered-anti Br Br Br H H HH H H Br H Br H 49.H H staggered-gauche H N H H H N H3CO-H H top Br Br 4 H H NH2 H2N H-OCH3 staggered-anti H H H Br Br H 2 1 Br H H 1 2 Br H Br H H BrBr 4 Br 48.2 pm). . and the boat conformations are the lowest. and the steric repulsion will elongate or at least distort the three-membered ring to accommodate the six chlorine atoms. molecular modeling indicates the C-C bond distance in cyclopropane is 1. the C-C bonds in hexachlorocyclopropane are expected to be weaker when compared to cyclopropane. and the boat conformation that has hydrogen atoms in the flagpole positions (circled) has the least amount of transannular strain. Cl H Cl H Cl H Cl H H Cl H Cl H Cl H H 51. For this reason.502Å (150. The flat structures are the highest in energy. Indeed.2 pm) whereas the C-C bond distance in hexachlorocyclopropane is 1.
but a H-H interaction in the other. CH3 Cl Br H H Br Cl Cl Cl Br 1 4 5 Br6 H 1 H 5 2 6 CH B 2 3 62 A H H H 4 Cl 3 Br 3 1 5 3 Br 4 H Cl H H CH3 H H H H . Since we do not know the relative steric demands of the substituents. Br Br H Br Br Br H Br H Br Br Br H Br H H 54. there is a Br-Br interaction in one boat. There are two boat conformations in equilibrium. Therefore. 53. which is less than the transannular stain in the molecule circled. Conformation A has 3 three axial groups (Cl. the equilibrium should favor more B and less A. we must simply count the number of axial groups. the H-Br transannular interaction is much less. Cl). The molecule that is circled has two bromine atoms on each carbon. In the other two molecules. so both boat conformations will have the Br-Br transannular strain. In the third molecule. Me) and B has 2 axial groups (Br. and B has only 2. Br.Br Br Br Br 2 axial Br Br Br Br Br Br Br Br Br Br Br Br Br Br Br Br Br Br Br 2 axial Br 52.
2-difluoroethane H H H H anti F (c) 2.2.(a) butane H H CH3 H CH3 F H anti H3C CH3 H H FF H H H syn H H syn H (b).2-dimethoxyethane CH3 CH3 anti H3C H CH3 OMe H H anti H H OMe H H H CH3 H Et H H3C CH3 H3C H3C H syn H MeO CH3 H H H syn H (e) pentane anti Et CH3 H H H syn H (f) 1-chloropropane 55. 1. H H CH3 H Cl H anti Cl CH3 H H H syn H .3-tetramethylbutane (d) 1.3.
H (a) butane H CH3 H CH3 anti H CH3 H CH3 F F anti H H H F H CH3 CH3 anti H CH3 CH3 H OM e H H OM e H Et anti H H CH3 H CH3 Cl H anti H H Cl H H syn H H H H syn H syn H H F (b).2-difluoroethane H H H3C H CH3 (c) 2. . 1.3-tetramethylbutane H H H OM e (d) 18.104.22.168-dimethoxyethane H H (e) pentane Et H H (f) 1-chloropropane H CH3 H H syn CH3 CH3 OM e H anti syn CH3 H syn 56.
H H CH3 Br H H CH3 Br H H 300° H 0° . H H CMe3 CMe3 H H anti H H CMe3 H H syn CMe3 . 58.360° H H H CH3 H H Br 60° 270° 90° H H 240° CH3 H Br H H 120° 180° H H CH3 H H CH3 H H Br H Br 57.
and certainly not the amount of space that a methyl group actually occupies. The covalent radius of Cl is 99 pm and a methyl group has a covalent radius is 200 pm.59. which effectively raises the energy of the steric repulsion. one gets a twisted structure as shown that is much higher in energy than the extended structure obtained when all the bonds are anti. which is the source of the steric hindrance. However. When the bonds are all syn. The methyl group is larger. 61. Me (a) Br Me Et Me low E (c) OMe Et H (e) Cl Cl H F Cl H Me Me F H Cl OMe Me low E Et Me OMe Et Me high E Me (f) I OMe high E Br Me (d) OH H F low E I Me F I H low E OH Me I high E Me OH H OH Me H high E Br low E Me Br Et Et (b) low E H Et H H Et H high E high E 62. The space-filling molecular model shown is much better. and clearly indicates that the two terminal methyl groups effectively compete for the same space. . each chlorine atom has three unshared electron pairs that contribute to the Cl-Cl repulsion. The hand-held models do not show the actual size of the atoms. 60.
5E) 64.7octatetraene (3E. which requires even greater distortion of bond angles and bond distances. the molecule should exist primarily in the gauche conformation shown due to stabilization via internal hydrogen bonding. H OH OH H H H 65. intermolecular hydrogen bonding effectively makes the OH groups larger and the minimal conformation will have the OH groups anti in order to minimize steric hindrance. and the bond lengths must also be distorted. but in A it is not possible to flatten the molecule due to the bicyclic nature of the molecule. The trans C-C=C-C unit has the constraint that bond angles about each sp2 carbon atom is 120°. so there is a greater energy preference for the anti rotamer. In the gas phase. The C-C C -C unit is linear. The geometry of the C=C unit is planar. In the presence of water. which is simply too high in energy. assuming all bonds possible have an anti conformation. In the hydrogen bonding solvent methanol. The C=C unit in B can flatten out without distortion of the rest of the molecule. octane 3Z-octene 3E-octene 1. .63. whereas the 3Estereoisomer has the extended structure. Cyclcohexyne is worse. The Z-stereoisomer has the twist in the middle due to the C=C unit. the trans double bond requires the other two carbons to have their bond angles distorted.5. H H H-OH H O CH3 H H 66.3. intermolecular hydrogen bonding effectively increases the size of the OH group. which imposes severe constraints on the remainder of the molecule. All except 3Z-octene have an extended type structure. In other words. It is simply too high in energy to exist. To flatten the molecule would essentially squash the atoms together. 67.
The choice is not obvious. however.A B 68. Cl Cl H CH2CH2CH3 H3CH2CH2C Cl Cl H 72. In 3. the two Cl atoms will be anti.4-dichlorooctane. There does not appear to be a large difference. and each bond will effectively exist as an anti-rotamer. as will the two propyl groups.7-octatetrayne will be linear because each C C unit is linear: 71.5. 1. Br Br Br H Et H CHClEt or H3C H H3CBrHC H Br Cl Cl Br B A .3. 69. and there is no great difference in steric hindrance between methyl and ethyl. Two possibilities are shown. Attempting to confine three adjacent linear C C units to a ring would require sever distortion to the point that it is simply impossible. Each propyl group is only slightly larger than a methyl because there is rotation about each bond. H H3C CH3 H 70. The planar nature of these units makes them effectively larger than the methyl groups. The lowest energy rotamer will have the planar C=C units anti. but A may have a bit more steric hindrance because Br is larger than Cl. as shown in the extended conformation to the left.
5-tetramethyl-3. a nonpolar solvent that cannot form a hydrogen bond with the acid.Cl geminal Cl Cl Cl Cl Cl Cl Cl geminal Cl Cl Cl Cl vicinal Cl Cl Cl Cl Cl Cl geminal Cl vicinal Cl Cl Cl vicinal Cl 73. Intramolecular hydrogen bonding of the hydroxyl group and the acidic carboxyl proton is possible. as shown. The angular nature of the ether linkage allows an extended conformation in which all C-C bonds are anti. OH H OH OH OH H 75. The conformation is therefore driven by alignment of the sterically bulky groups.4-hexanediol shows that if the two very large tert-butyl groups align in an anti conformation to minimize steric hindrance. intramolecular hydrogen bonding is maximized. .2. Cl 74. In hexane solvent. then the two hydroxyl groups are also anti. In other words. Examination of 2. the intramolecular hydrogen bonding overrides the normal syn-anti conformations. so it is assumed that 3-hydroxybutanoic acid assumes a conformation similar to that shown. O 76.5.
The conformation is not obvious. The hydrogen atoms indicated in all three molecules are sufficiently close that there are transannular interactions. H H O O H O H O H H 78. followed by (b). and chair cyclohexane has none. The order is likely (f) > (b) > (a) > (e) > (c) > (d). The order is (a) > (b) > (f) > (e) > (c) > (d). planar cyclohexane has more than cyclopropane or cyclobutane. as does (e). aldehydes are capable of internal dipole-dipole interactions. CH3 CH3 H H CH 3 H H H H CH3 H H H H CH3 CH3 CH3 CH3 . Note that this is an educated guess. The representative transannular interactions are marked in each structure. The reasons for this problem is to emphasize that conformation is often the result of complex interactions. The planar nature of the C=O units may lead to the two CHO groups in an anti relationship. However. and sometimes the correct answer is. Planar structure (a) has some Baeyer strain. (f) has the most. and the rather simple analysis done here cannot give the answer. H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H (a) H H H H H (b) H H (c) HH H H H H H H H H H H H HH (d) H H (e) H H H H H (f) 79.H H O O O 77. In terms of torsion strain. and a gauche rotamer is shown with the assumption that this conformation may have more stability. I don’t know for sure. In terms of Bayer strain.
4-dimethylcyclohexane . In cis-1. This means that the difference in A-strain for isopropyl versus methyl is not necessarily as great as might be expected. will have a greater amount of A-strain. This phenomenon is due to rotation about the C-C bonds (ring carbon-CHMe2) to minimize steric interactions. with the larger isopropyl groups. which imposes a high energy barrier due to A-strain. the transannular interaction involves methyl-hydrogen in both conformations. the cis-isomer will have a large preference for the lower energy conformation. however. however. as shown. In trans-1. Therefore.2-di-tert-butylcyclohexane requires that one of the very bulky tertbutyl groups assume an axial position. It appears that the diisopropyl derivative. versus 83. 81. which removes the A-strain and is much lower in energy.4-dimethylcyclohexane.(a) (b) (c) (d) 80. both tert-butyl groups are “pseudo equatorial”. In the boat conformation. Either chair conformation of 1. one conformation has a methylmethyl transannular interaction and the other has a hydrogen-hydrogen interaction that is much lower in energy than the conformation with methyl interactions. The energy of each conformation is about the same. so there should be a roughly equal amount of each conformer. H CH3 H CH3 H3C H trans H H3C CH3 H3C H cisH3C H H CH3 H 82. . The methyl groups will spend more time “outside” the ring cavity.
which imposes a great deal of A-strain.3-dibromocyclohexane cis-1. From the diagrams. it is clear that the boat conformation of 1.3-dimethylcyclohexane cis-1. which diminishes some of the transannular strain. Therefore. whereas the other chair confirmation has both groups equatorial.2-diisopropylcyclohexane will exist primary as the diequatorial conformation with very little of the diaxial conformation. the A-strain is the same in both conformations. whereas reduction of the ketone to give the alcohol will introduce more transannular strain. Diinished transannular strain makes the oxidation more facile. H H cisH H H H H transH 85. This increased strain imposes a slight energy barrier to the reduction. . The space-filling models make this a little more apparent. Therefore. The two chair conformations of cis-1.cis-1.2-diisopropylcyclohexane. trans1. one chair conformation has both groups axial. Oxidation to the ketone flattens out the three carbons atoms associated with the carbonyl unit.4.1.5-hexamethylcycloheptane has some transannular strain because the methyl groups are closer together than in the chair conformation.5. and there should be a roughly equal amount of each. which makes it a bit more difficult. and cyclooctanol also has this transannular strain.3-diisopropylcyclohexane 84.4. Cyclcooctane has a relatively high amount of transannular strain. CH3 CH3 CH3 CH3 CH3 H3C H3C CH3 H3C CH3 H3C chair CH3 boat 86. The latter is much lower in energy because it has no A-strain. In trans-1.2-diisopropylcyclohexane show that one group is axial and one is equatorial in each conformation.
Therefore. H H H3C H H H CH3 H H H CH3 H H H CH 3 H 88.H H H H H H HH H H H H H H H H oxidation OH reduction H H H H H H H H H H HH H O 87. there is a relatively high percentage of this particular boat conformation. they are expected to have roughly the same energy and one will not be present in greater amount than the other. The A-strain is the source of the energy barrier mentioned in the question.4-dimethylcyclohex-2-ene show that there is one pseudo-axial methyl and one pseudo-equatorial methyl in both conformations. CH3 CH2 H H H H H 89. Conversion of the flat C=C unit to the methyl group introduces A-strain in methylcyclohexane. which stabilizes that conformation. The two chair conformations of cis-1.4-cyclohexanedicarboxylic acid (shown) has internal hydrogen bonding between the two carboxyl groups. One boat conformation of cis-1. Therefore. HO H O HO O H . which means that it is higher in energy than methylenecyclohexane.
This simplistic explanation indicates that the electron pair interaction is higher in energy than the A-strain imposed by the axial methoxy group. In 2-methoxypyran (B) you can imagine an interaction of the lone electron pairs on the two oxygen atoms when the OMe group is equatorial (B’). but based on what is known from this chapter. as noted in the question. which is minimized when the OMe group is axial. O A OMe OMe B MeO O B' . Methoxycyclohexane (A) exists primarily in the chair conformation due to diminished A-strain when compared to the conformation with the OMe group axial. it is a reasonable explanation. this is an overly simplistic explanation for a more complicated issue.90.
The molecule shown has a carbon atom with four different groups attached.4. 39. so x = 1-y. then –20° = x(+100°) + y(–100°). Therefore. In the molecule marked CHBrF. Cl. and –120° = –200°y.it is a trick. Br. so y = –120°/–200°. Assume that A + A’ = 1. The ratio is therefore 60:40. and x+y = 1. Therefore. so x = 0. then [ ] for the (S)-enantiomer has the same magnitude but with the opposite sign.5(–° S) = 0°. then 0. All contribute to specific rotation except group priority. The circled molecule has four different atoms or groups (H.CHAPTER 9 36. +10° –10° +20° –20° 0° +4° –4° 42.75. then A = 0. If the specific rotation of a mixture of both enantiomers is – 20°. so the carbon is a stereogenic center. and –20°–100° = –200°y. If the specific rotation of a pure enantiomer is +100°. OH). so A’ = -105°/–140° = 0. which is +50°.5(+° R) + 0. The [ ] for a racemic mixture is always 0° because racemic mixture is a 50:50 mixture of both enantiomers. and it is not a real molecule . so A = 1-A’ (1-A’)(+70°) + A’(–70°). or 25% of A and 75% of A’. FCH2CH2Br CCl4 CHBrF BrCHClOH c (a) (b) CH2CH2Br CH2CH2OH CH2CHBrCH3 CH2CHBrCH3 b d CH2CH2CH2CH2OH CH2CH2CH2CH2I a CH2F CH2CH3 37. 0. and y = 0. +100° -100° +50° -50° 0° 43. path length group priority concentration 40. +50° -50° +5° -5° 0° 41. carbon has only three substituents.6(–20°) + 0. then specific rotation for the other enantiomer is –100°. so 70° –70°A’ – 70°A’ = –35° –140°A’ = –35°-140° = –105°. If A’ = 0. –20° = 1-y(+100°)-100°y and –20° = 100°–100°y–100°y. or –20° = 100°–200°y. 20:80 30:70 10:90 40:60 50:50 . and the molecule is chiral. b a c d 38.75. If [ ] for R is -20°.4(+20°) = [ ] for a mixture of enantiomers = –12°+8° = –4°.25. A(+70°) + A’(–70°) = –35°C. If [ ] for the (R)-enantiomer of a molecule is –50°.6.
Br (a) (b) Cl chiral .no enantiomer (d) meso compound. and therefore they cannot be used for determining [ ] of a compound in a polarimeter. so it has a superimposable mirror image . OH (c) not a stereogenic center. H O H HO has a chiral center H2O O H CH3 Cl Cl H has a chiral center Me Br (c) (R) (S) (R) (R) Et (R) (a) OH (S) (S) (b) Cl CH2Br (f) (S) (S) (R) HO (e) (S) (d) Et O C3H7 (S) CH3 OH NH2 46. The circled solvents each have a stereogenic center.has an enantiomer Br Br Br 47. therefore it has a superomposable mirror image .no enantiomer Br chiral .has an enantiomer .44. Which of the following is the enantiomer of (2R)-bromohexane? Br (R) Br (S) (S) (R) 2-bromohexane 2-bromohexane Br 3-bromohexane Br 3-bromohexane 45.
CH3 H (a) 3R-bromo-2S-hexanol H (S) (R) OH Br (b) 4R-methyldodecane CHCH2CH3 H3C (R) H CH2CH3 CH3 Cl (c) 2R. so it has a sumperimposable mirror image .Me (e) OH OH OH OH (f) OH Me symmeetrical. 49.3S.4R-trichlorooctane H H (R) (S) (R) C7H15 H Cl Cl (d) 3S-heptanol H CH2CH3 (S) OH CH2CH2CH2CH3 C H2CH2CH3 CH2CH3 (e) 3R-ethyl-3-methyloctane H3C A trick! C3 has two ethyl groups. so there is no sterogenic center CH2CH3 CH2CH2CH2CH2CH3 (f) hept-1-en-3R-ol H (R) OH CH2CH2CH2CH3 .no enantiomer OH H OH non-superimposable. so it is chiral and it has an enantiomer OH (a) H3C H3C Cl (b) Cl HO H3C * * ** * OH H Cl 2 22 23 24 25 26 OH * * * * H 23 H 24 25 26 27 28 * 48.
D D S(–208°) + R(+208°) = –118°C.567.6°). (b) [ ]20 = -166° for the R-enantiomer and [ ]20 = -154° for the mixture. so S = 1-R (1-R)(+18. so S = 1-R (1-R)(–208°) + R(208°) = –118°.5) = –0. (d) [ ]20 = +208° for the R-enantiomer and [ ]20 = -118° for the mixture.6° 52.4% S. (c) [ ]20 = -45° for the S-enantiomer and [ ]20 = +27° for the mixture.4% R and 3. Assume that S + R = 1. 56.6° –18. Therefore.6°A’ = –2.6°) + R(–18.2° = –21. which means that the specific rotation is 0°.6° for the S-enantiomer and [ ]20 = -2.10° (d) +94°/(2.7. so R = 90°/416° = 0. 56% ee S. 22% R and 78% S.4°/(5. In all cases. If the product is a racemate. but it will have the opposite sign: +77°.22.7. Therefore. so R = 72°/90° = 0. convert cm to decimeters.5° 18.6°) + R(–18.3 x 3.8. the D product will be the R enantiomer. Therefore. then there is a 50:50 mixture of the R and S enantiomers. Using Figure 9.4 x 2. so S = 1-R (1-R)(–45°) + 45° = +27°.5) = +6. 53. 60% ee R.5°-18.5°C.1/–37. so –45°+45°R +45°R = +27° 90°R = 27°+45°. D D S(–45°) + R(+45°) = +27°C.7. and the specific rotation will have the same magnitude as that for the S-enantiomer. so 416°R = 90°. (a) +18°/(1. Using Figure 9.6°A’ –18. 54. HO (a) CH3 CH2Br (R) Me3C (b) (R) CH2CH3 CHMe2 (c) Cl H (R) CH2Br Br (d) H HO (R) (S) NH2 Me CH2CH3 Br CH3 Et CH=CH2 (R) CH2CHMe2 H (h) H CH2CH2CH2Br (S) (e) (S) (f) Me2HC H (g) (R) Me C C-CH3 OH CH2OH CHMe2 51.0) = +13.50. 15% ee R. so 166°–166°R–166°R = –154° –332°R = –154°–166°. Therefore. so –332°R = 320°.6°/–37.5°. Assume that S + R = 1.7.3 x 5.6% S. so 90°R = 72°. so S = 1-R 1-R(166°)–166°R = –154°. Assume that S + R = 1.1x2. so 416°R = –118°+208°. 96. D D S(+18. .6° –37. Using Figure 9. so R = -2.3° (c) –1. 1 cm 0. Using Figure 9. so 18.6°) = –2.2°R = –2. Calculate the percentage of each enantiomer and the %ee for the mixture given the following information. Assume that S + R = 1. D D S(+166°) + R(–166°) = –154°C. 80% R and 20% S. If t [ ]20 = –77° for the S-enantiomer and it reacts to give a product with complete inversion. so R = 320°/–332° = 0. so –208°+208°R+208°R = –118° –208°+416°R = –118°.1 dm.7% R and 43.0) = –117. (a) [ ]20 = +18. 98% ee R.55° (b) –176°/0.5° for the mixture.964.2 = 0.
6E-dien-2-one O (Z) (E) Br (E) 57.3-diphenyl-4E-nonen-1-ol (E) (b) 2. a Z double bond. OCH3 O O CH3 (R) (b) (a) (c) (R) (R) (S) (S) CHMe2 OH H (S) OH (e) (S) (S) NHMe (f) N •• Me CH3 OH (S) (S) (d) Me H MeO Me O H N •• (S) 56.3. F . Determine the absolute configuration of each stereogenic carbon in the following molecules. Determine if each of the following alkenes has an E.55.4. Et (Z) (a) no E/Z isomers are possible (d) Et (b) (E) (c) Cl HO (e) C3H7 (Z) Cl (f) (E) (a) 3. or if it has no stereoisomers.5-tetrachlorohex-2Z-ene Cl OH Cl Cl (Z) Ph Ph Cl (d) 3-ethylhept-2E-ene (c) 3-bromo-6-fluorodeca-3Z.
3-dibromo-2Z-pentene cis-2.4-dichlorohex-3Z-ene Cl (Z) (E) Cl 58.(e) 5-(1-methylethyl)-4-(2. Br (a) (Z) Et Br (b) (Z) (Z) (c) CH2Cl 3-(chloromethyl)-3Z-hexene trans-3-(chloromethyl)-3-hexene OH (E) 2.3-dibromo-2-pentene overlap (E) 3-ethyl-3Z-octene cis-3-ethyl-3-octene overlap (d) Et 4-ethyl-3E-heptene cis-4-ethyl-3-heptene (e) Me (Z) (f) 3-ethyl-4. E = enantiomers. (a) 3.5-dimethyl-2Z-hexene 4-(1-methylethyl)-6-methylhep-4E-en-3-ol cis-4-(1-methylethyl)-6-methylhep-4-en-3-ol 59.2-dimethylpropyl)dodec-4Z-ene (f) 3.4-dichloroheptane CH2CH3 H H D H Cl (S) (R) (b) 2-bromo-3-methylhexane CH2CH3 H H3C (S) (S) CH2CH3 E Cl Cl (R) (S) CH2CH3 E Br H (R) (R) Cl Cl H H D Br H H CH3 D CH2CH2CH3 CH2CH3 (S) (S) CH2CH2CH3 CH2CH3 (R) (R) D H H CH2CH3 CH2CH3 (S) (R) CH2CH3 CH2CH3 E Br H3C (R) (S) Cl H E Cl H H Cl Br CH3 H H CH2CH2CH3 CH2CH2CH3 CH2CH3 CH2CH3 . M = meso. D = diastereomers.
4-dibromohexane CH2CH3 CH2CH3 H H D D H Br (S) (R) OH Ph E HO Ph H H Br Br M Br Br (R) (S) H H D CH2CH2CH3 CH2CH3 (S) (R) CH2CH2CH3 CH2CH3 (R) (S) CH2CH3 CH2CH3 (S) (S) CH2CH3 CH2CH3 E Br H (R) (R) OH H E HO H H Ph Br H H Br CH2CH2CH3 (e) 2.5-hexanediol CH3 CH2CH2CH3 CH2CH3 (f) 3.5-heptanetriol CH2CH3 CH3 (R) H H H H D H H H HO (S) OH H H HO M H H HO H H H CH2CH3 H H H D H HO H D D H H HO (S) (S) (s) (R) CH2CH3 HO M HO HO (R) (s) (S) OH OH OH H H H D (R) OH (S) H D CH3 CH3 (S) CH3 CH3 OH H H E HO H H H (R) (R) CH2CH3 CH2CH3 (S) (r) (R) CH2CH3 CH2CH3 HO E H HO (R) (r) (S) H H H OH OH H OH H OH H (S) H CH2CH3 CH2CH3 (S) CH2CH3 D CH2CH3 HO E HO H (R) (R) CH3 D CH2CH3 H HO HO (S) (S) CH3 CH2CH3 HO E H H (R) (R) OH OH H H H OH OH H H H OH OH CH2CH3 CH2CH3 CH2CH3 CH2CH3 .4.(c) 4-phenyl-3-heptanol CH2CH3 H H D H Ph (S) (S) CH2CH3 (R) (R) (d) 3.
CH3 H H (g) 2-bromo-5-methylhexane H H CH3 (h) 2.3.4. One of the diastereomers is a meso compound. then it will exist as a 50:50 mixture of R:S enantiomers. meso CO2Et CO2Et H O EtO OH O H diethyl tartrate HO OH OEt H (R) (S) OH OH HO HO (S) (R) H H CO2Et CO2Et (R) (R) CO2Et CO2Et HO H (S) (S) OH H H OH CO2Et CO2Et 61. . Only the chiral diastereomer can be used. If ibuprofen racemizes. and the specific rotation will = 0°. which cannot be used in reactions because it is not a chiral molecule. Both enantiomers are shown.5-tetramethylhexane CHMe2 H H (S) (R) (S) CH3 Br H H CH3 E Br H H H3C CH3 (R) H H H H CHMe2 H3C H3C M (R) (S) CHMe2 H H3C D (S) (S) CHMe2 H3C E H (R) (R) CH3 CH3 H H CH3 H H CH3 CHMe2 CHMe2 CHMe2 CHMe2 60.
or the mirror image of the ring flip conformation.5. In (a).4. as are their mirror images. Compound (d) has two enantiomers and the two different chairs are diastereomers of each other.Ibuprofen (R) (S) (S) HOOC Me Me COOH HOOC Me (a) 2. (b) and (c) there are superimposable structures.8-nonanetriol CH3 CH3 meso CH2CH3 (R) (R) (S) CH2CH3 H H H (S) (S) (R) H H H H H H (S) OH H HO H HO H H HO (R) H H OH OH OH H H H (R) OH H H (S) H H H CH2CH2CH2CH3 CH2CH2CH2CH3 (R) OH (S) H 62. either the mirror image. all of these are meso compounds and the structures shown represent one single structure.5-nonanetriol meso HO HO HO CH3 (d) 2. CH3 CH3 63.2-dibromocyclopentane CH3 HO HO (R) (S) meso OH OH meso H H (R) Br Br Br Br (S) (S) (R) CH3 (c) 3. Therefore.3-butanediol CH3 H H (S) (R) (b) 1. .
(a) cis-2-chlorocyclohexanol Cl Cl (b) trans-1.4-dimethylcyclohexane CH3 CH3 Cl Cl superimposable CH3 CH3 superimposable H3C CH3 Cl Cl superimposable Cl Cl H3C superimposable CH3 (c) cis-1.3-cyclohexanediol OH OH superimposable OH OH (d) cis-1-bromo-2-chlorocyclohexane Br Br enantiomers Cl Cl all diastereomers Cl OH Cl superimposable HO OH HO enantiomers Br Br H H (a) O (R) (R) O N Me (S) OH (S) H O C8H19 (S) HO (b) (R) (S) O O (S) (R) (S) (S) (R) (R) O O (c) 23 HO (d) (R) O H CO2H (S) (R) 24 27 (S) HO N •• OH OH OH CO2H (f) OH HO2C (S) (S) (e) (S) (S) (S) (S) HO (S) OH 64. 24 OH 23 23 HO2C N H OH .
9dichlorobicyclo[3.2. Name each of the following (1R.3S.5S)-9.3.5-dimethylbicyclo[2.1]hexan-1-ol Cl (d) (Z) (R) (S) (a) (c) (s) (s) H (1S.1.E)-4-bromo-1-chloro-5methylhepta-1.2.3adimethyloctahydropentalene (1R.2S.5R.0]octane .4R)-1-cyclopropyl-3methyl-4-phenylhexan-1-ol Br Me (3R.5-diene Cl H Me (f) H Cl (R) (S) Cl (S) (R) (e) (S) (R) (R) Me H (3aR. Give an unambiguous IUPAC name to each of the following.6aS)-2.7-dichlorobicyclo[4.3S.4S)-bicyclo[2.65.5R.0]hexane H Et (S) (b) Et OH (4S)-5.3-diethylbicyclo[3.6-diene 66.5S)-3.E)-5-isopropyl-3-methyloct6-enoic acid O (e) (R) (R) (R) CHO (2S.1]non-2-ene (1R.1.4S)-2-ethyl-3.7R)-5-bromo-3-methyl7-phenyloctan-2-one Me (4R.6R)-2.2]octa-2.5R.4dimethylhex-5-ynal Br (f) Cl (E) (R) (R) Ph (1S. OH (a) (R) (b) (E) (R) (R) (c) CO2H (S) (S) (S) (R)-2-methylpentan-3-ol Ph HO (d) (S) (S) (R) (3R.
Br (S) H (S) H Br CH3 CH3 CH3 CH2CH3 CH3 Br Br HO (S) CH3 H3C O CH2CH2OH (S) F (H3C)3C (R) CH2CH3 Cl Br Br Cl (R) CH2OH H3C C CCH3 (S) Br H H (R) H3C Me2HC (S) CH2CHMe2 CH2CMe3 OH H CH2OH CH2CH2CH2Br HO (S) Br CH3 CN CH3 Br (R) CH2CH2I (R) Cl (R) H3C H3CH2C Cl (S) OH C CCH3 CN H3C Me2HC CH2CHMe2 (S) H Br Br CH2OH CH2CH2CH2Br CH2CH2CH3 (S) CH(CH3)2 CH2CMe3 .3R CH3 Br Br (R) (S) Cl CH2CH3 CH3 H H Br H (R) (R) CH3 H Br H H (S) (R) CH2CH3 Br Br H H (S) (R) CH3 Br Br 68.3S) CH3 Br (S) COOH 2R. mirror image (2S. 69.CH3 Cl (S) meso CH3 H H (S) (R) CH3 Br Br Br H (R) (R) CH2CH3 H Br H H (S) (R) meso CH2CH3 H H (S) (R) CH3 Cl Cl Cl Cl H (R) Br H CH3 COOH H H (S) (R) CH3 CH2CH3 Cl H (R) (S) CH3 meso H CH2CH3 Cl Cl CH2CH3 CH2CH3 (R) (S) meso Br Br H H 67.
2. (2S.1]nonane (1r.6S)-bicyclo[4. Br . this constitutes one compound CH3 CH3 (R) (R) (S) (S) (2R.1.4-dichlorohexane Cl (R) (S) (R) Cl (S) Cl meso Cl 70.2]nonane octahydro-1Hindene 72.3S)-2-bromo-3-methylhexane (S) 71.5s)-bicyclo[3.5r)-bicyclo[3.3R)-2-bromo-3-methylhexane Br Br (2R.1]heptane bicyclo[3.4-dichlorohexane Cl Cl (3S.3S)-2-bromo-3-methylhexane (1R.4-dichlorohexane (3R.4R)-3. OH (1s.1]nonane (H3C)3C CH2CH3 (c) H (S) (R) Cl (S) CH3 (a) (R) H CH2CH2CH3 (b) H CH3 Br Br Cl CH2CH2CH2OH OH CH(CH3)2 H (S) (R) Br Br (d) Br H (e) CH3 (S) (f) (R) H H3C CH(CH3)2 73.4S)-3.3.3R)-2-bromo-3-methylhexane CH3 (R) Br Br CH3 (R) (S) (2S.Cl (R) (R) (S) Cl (S) (3R.4S)-3.2.
76. the specific rotation is 0°.Cl (R) CH(CH3)2 H (S) HO (R) CH3 H C C-CH3 Cl Cl CH2OH Cl H H (S) (R) CH2CH3 Br H3C (R) (S) Br Br CH3 CH(CH3)2 CH2CH2CH2OH HO (S) CH3 CN Br H (R) (S) Br CH3 H Cl CH(CH3)2 (R) CH2CMe3 BrH2CH2C (R) (R) CH3 CN Cl H3C H CH2CH2CH2Cl CH2CH2Cl CH3 CH2CH2CH2OH HO (R) H Br (S) (S) Br H H2N (R) H CH3 CH2CH2CH2CH2Br CH2CMe3 74. CH3 CH3 Cl (S) (R) (S) (R) Et Et meso OH Br (R) Cl CH3 CH3 Cl Et HO meso (S) Et Cl (R) (S) CH3 meso CH3 (S) (R) OH (R) (R) Cl Cl Et Et CH3 OH 75. enantiomer diastereomer racemic Cl enantiopure 77. . Since 2Z-3-methyl-2-pentene has no stereogenic center.
3R. Using Figure 9.4-dibromohexane CH2CH3 Br Br H H (S) (R) CH3 Br Br Br Br 78.5R-heptanetriol CH2CH3 H H H (S) (s) (R) CH2CH3 Br H (R) (R) HO H H H H H H H Br OH OH OH CH2CH3 (g) 2S-bromo-5S-methylhexane CH3 H H H H (S) (R) OH CH3 CH3 Br H H CH3 CH3 This is a trick question. 4. becasue C5 is not a stereogenic center.5% ee R (d) 75:25 R:S = 50% ee R 81.4R-dibromohexane CH2CH2CH3 (e) 2R.CH3 Br (S) meso CH3 (R) (S) CH3 H H Br H (R) (R) meso CH3 H Br H H (S) (R) this is 3.5-tetramethylhexane CH3 H CH3 CH3 79. 80. S(+100°) + R(–100°) = +91°C. Therefore.5% R and 95.5% S.4R.4S-dichloroheptane CH2CH3 H Cl (S) (S) (b) 2R-bromo-3S-methylhexane CH3 Br H3C (R) (S) Cl H H H HO Ph H H CHCH2CH3 (d) 3R.7. H H3C H H CH3 (R) (R) CH2CH3 (h) 2. H (S) H Br CH3 CH3 CH3 CH2CH3 (c) 4R-phenyl-3R-heptanol CH2CH3 (R) (R) (a) 3S.045 Therefore. and –200°R = –9°.5R-hexanediol CH3 (R) CHCH2CH3 (f) 3S. Assume that S + R = 1. so –200°R = 91°–100°. and R = –9°/–200° = 0. so 100°–100°R–100°R = 91° 100°–200°R = 91°.4S. Using Figure 9. 92% ee S.7: (a) 82:18 R:S = 62% ee R (b) 55:45 R:S = 10% ee R (c) 99:1 R:S = >99. there is no 5S. so S = 1-R (1-R)(100°) + R(–100°) = 91°. .
83. Determine the absolute configuration for each nitrogen atom in the following molecules. The term 0% indicates there is no excess of one enantiomer over the other. which means that it is a 50:50 mixture (racemic). CH3 •• Ph HO (S) CH3 (R) (R) OH H N (S) (R) (S) (R) N •• (R) CH3 (R) (a) (b) (c) (d) •• N (R) H (R) (S) N (S) Ph H (S) N •• N Ph (S) (S) (S) (R) CH3 •• H3C (E) •• CH2CH=CH2 H3C OH Cl . 84. It simply means that fluxional inversion is much more difficult with phosphines when compared with amines.82.
57. Only an alkyne will react with HBr to give a vinyl bromide. allylic cation resonance stabilized 61. A peroxyacid is required to convert an alkene to an epoxide. . The circled alkene is the most highly substituted (the most carbon substituents). C CH 59. The two alkynes are circled. CH3OH CH3CO2H CH3CO3H NaOH least stable most stable 60. Carbon substituents are electron releasing with respect to a -bond.CHAPTER 10 56. Br2 HCl BH3 CH3CO3H H2O 58. so the more carbon substituents. 62. and the more stable it will be. the more electron rich the -bond.
3-dimethyl-2-butene is more stable than the secondary carbocation derived from 2-butene. Br2 BH3 OsO4 H2O/HgCl2 HCl Cl2 Cl (E) Cl 64. Cyclohexene is symmetrical. Carbocation A is much more stable as an intermediate. it will react faster with HCl. and will give the . and there is effectively only one product.5-hexadiene to give the chloride shown.3° more stable so no rearrngement no cation is more stable. In other words. Cl Cl 67. so no rearrangement can rearrange to a more stable 3° cation can rearrange to a more stable 3° cation 63.3-Dimethylbutene reacts faster with HCl than does 2-butene because it is an acid-base reaction. no rearrangement is possible to produce a more stable carbocation once the C=C unit is converted to C-C+.3-dimethyl-2-butene leads to a more electron rich p-bond. whereas A is a benzylic carbocation where the charge is delocalized into two benzene rings. Of these reagents. and the increased stability should lead to a lower activation energy and a faster reaction. In addition. via carbocation A. 66. which makes it a stronger base. a cis-dichloride a trans-dichloride an E-mono-chloride a Z-mono-chloride 65. will form preferentially over B. and the more highly substituted C=C unit in 2. Addition of one equivalent of HCl will add to 1. In other words. the tertiary carbocation intermediate derived from 2. Reaction with the other C=C unit generates a secondary carbocation B. only borane adds to alkenes or alkynes in an anti-Markovnikov manner.1-diphenyl-1. 2.
leaving behind C+ and placing the electron pair on oxygen. The reaction of 2-methyl-2-propene with acid will generate a tertiary carbocation. Two resonance contributors are drawn. one with the charge on oxygen after reaction with the acid. the tertiary carbocation is formed. In both reactions. Reaction of acetone with an acid generates the resonance stabilized oxocarbenium ion shown. Under these conditions. if the hydrogen sulfate anion reacts with the carbocation. which is relatively stable. In the case of HCl. and the second contributor with the charge on carbon. the hydrogen sulfate anion reacts as a base to remove a proton from the carbon adjacent to C+. This latter reaction is known as an E1 reaction. the hydrogen sulfate product is rather unstable. The resonance stabilized oxocarbenium ion is much more stable that the tertiary carbocation. In the case of sulfuric acid. reacting with the carbocation to generate the chloride product. and fragments to regenerate the carbocation. chloride ion is a good nucleophile.major product shown. . H2SO4 HCl Cl 70. H O H O O 69. HCl A a resonance stabilized benzylic carbocation HCl Cl B 68. which is generated by transfer of the two electrons in the -bond to oxygen. generating the alkene. and a weak nucleophile. they hydrogen sulfate anion is resonance stabilized. and will be discussed in chapter 12. In addition.
which is more stable than the original tertiary carbocation OCH3 HCl OCH3 OCH3 Cl an oxocarbenium ion 71. ClCH2CH2Cl CF3CO2H . 0°C Me Me H Me H H O Me OH A B 73. so there is essentially no driving force to react with an alkene bond. The alkyne unit in A will ultimately react with a carbocation to form a vinyl carbocation. the allylic alcohol leads to a resonance stabilized allylic carbocation. and will quickly react with water to give an enol.2-alkyl shift generates a tertiary benzylic carbocation. Diatomic nitrogen is not similarly polarized. which leads tot the ionic bromonium ion intermediate. The steric hindrance in the alkene is perhaps better seen in the molecular models of A that are provided. 74. so similar reaction does not occur. In A. Me C C Me HOCH2CH2OH . Vinyl carbocations are much more reactive. the isopropyl groups will sterically hindered approach of the nucleophile to the C+.Br HBr Br– a 1. again limiting the amount of product formed. This latter reactions will effectively stop the cation cyclization process. especially the space-filling model on the right. Diatomic bromine has the polarizable bromine atom. Molecule A has relatively large isopropyl groups that block approach of the C=C unit to any acid. and proximity to a -bond leads to a polarized Br-Br bond. If the carbocation does form. 72. Nitrogen is not a polarizable atom. to generate a secondary carbocation. therefore. formation of the carbocation is sluggish. which tautomerizes to a ketone. and the tertiary cation site is more reactive when reaction occurs with the next C=C unit. .
CCl4 Br via rearrangement of the initially formed 2° cation Cl (e) HCl OEt (d) cat.H H H H H H H H C=C 75. CCl4 I I . The major product or products are shown in each case. p-TsOH EtOH (f) I2 . Cl HCl + (a) Cl (b) HBr Br Br (c) Br2 . No mechanisms are provided.
and loss of a proton. BH3 . in an acid-base reaction (probably with ethanol as the base. Initial reaction with HCl generates the 2° vinyl carbocation. Subsequent reaction with the nucleophilic oxygen atom of ethanol leads to an oxonium. CCl4 Br Cl Br HCl OEt OH Cl (h) (i) via rearrangement of the initially formed 2° cation (j) cat TsOH EtOH . THF Br2 . It is difficult to predict endo. No mechanisms are provided. In principle. heat via rearrangement of the initially formed 2° cation 76. ether 2. The predicted higher energy of the product suggests that the reaction will have a high activation energy and/or maybe endothermic. 9-BBN . and the anticipated trans-dibromide product will generate a trans C=C unit in the cyclooctene product. and the entropy of the reaction. this product should be rather high in energy. due to the constraints of the ring and the geometric demands to the trans. Br2 Br Br 78. or another molecule of the alkyne) leads to the vinyl ether product.double bond. ether 2.versus exothermic energy without looking at the enthalpy. The major product or products for each reaction are shown.(g) HOCl aq. (a) 1. cat. NaOH 1. NaOH . H2O2 OH (b) OH . H+ H-OEt O H – H+ O 77. H2O2 . formation of the bromonium ion.
NaOH . excess O3 .H (c) 1. formed from the “bottom” is essentially free of steric hindrance. 9-BBN . H2O2 (h) HO2C O OH (i) OsO4 . –78°C 2. there is severe steric hindrance between a methyl group and the bulky 9-BBN unit. Me2S OHC O O OH + formaldehyde 79. ether 2. O3 . O3 . H3PO4 H via enol O (f) + O via enol O O (g) HCO3H aq THF 1. H2O2 HgSO4 . with 9-BBN leads two possible transition states. . Me2S HBr t-BuOOt-Bu + O Br O (d) (e) 1. whereas the other transition state. the lower transition state predominates to give the alkylborane shown. In one. aq t-BuOOH (j) 1. from the “top” face. so hydroboration occurs at either carbon of the C=C unit to give to the same product. –78°C 2. Molecule A is symmetrical. Therefore. and oxidation gives the alcohol as the major product. Hg(OAc)2 H2O . –78°C 2.
Me Me CH2 H2O H O H OH cat. H+ Me Me CH3 Me Me CH3 (a) 1-ethylcycloheptene OH (b) 2-phenyl-1-butene Ph Ph OH 81. .Me steric hindrance Me B H Me Me BH3 Me A versus Me Me Me oxidation B H Me Me B OH 80.
I2 . The major product or products are shown. H2O2 O + O OH OH H (c) OsO4 .(c) 3.4-diethyl-3-hexene OH (d) 3. CCl4 Br racemic Br NaOH (e) ether HOCl H2 O2 (f) OH Cl OH . –78°C 2.3-dimethyl-1-hexyne C3H7 C3H7 OH C3H7 O H 82. Me3COOH (d) H B Br2 . No mechanisms are provided. O3 . CCl4 I I (a) (b) 1.
CCl4 racemic Cl . CCl4 racemic Br (p) (q) HBr Br Cl Cl2 . CCl4 H + HCO2H I I (k) (l) catalytic H2SO4 H2 O OH (m) HBr Br Cl (n) HCl via rearrangement of the initially formed 2° cation Br (o) Br2 . CCl4 HBr (i) O Br O O O H (j) I2 .O (g) H O O H + HCO2H O Br racemic Br (h) Br2 .
R. H+ OH (e) H2O (f) 2 HBr . Give the major product for each reaction.(r) 1. CCl4 no reaction (N. CH3SCH3 CH3CO3H O CHO O (s) + CH3CO2H 83. CCl4 I OH (d) HOCl Cl H2O . HBr Br (a) Br (b) Br2 CCl4 Br I racemic (c) I2 . O3 . –78°C 2.) (g) HCl Cl Br Br (h) via rearrangement of the initially formed 2° cation . cat.
CCl4 2. via carbocation. with rearrangement from initially formed 2° cation . NaBH4 no rearrangement HO2C O (j) 1. BH3 . O3 . HgSO4 + O OH H O O (n) OsO4 (o) OH OH NaHSO3 . ether (p) 2. –78°C 2. BH3 . H2O2 OH I O H (q) HI (r) (s) H Me H2 . O3 . H2O2 H2O . H2O 1. NaOH . H2O2 1. NaOH . ether (k) Br2 . H2O (i) 2. Pd-C EtOH HBr Br Me racemic. HgCl2 . H2O2 OH Br racemic Br (l) (m) 1.1. –78°C 2.
Hg(OAc)2 . Hg(OAc)2 . H2O 2. NaOH . H2O2 OH OH (a) Ph (b) 1. 1. H2O 2. NaBH4 Ph 1. H2O 1. NaBH4 OH (d) 1. NaOH . BH3 . NaBH4 OH .Br (t) Br2 . H2O2 OH OEt 84. NaBH4 OMe + Ph OMe (c) 1. EtOH 2. Hg(OAc)2 . (a) (b) 1. NaBH4 1. water 2. ether OH OH O H (v) 2. BH3 . CCl4 racemic Br (u) OsO4 NaHSO3 . MeOH 2. Hg(OAc)2 . water 2. Hg(OAc)2 . Hg(OAc)2 . ether 2. NaBH4 OH (c) 85.
H2O2 OH (e) 1. Me2S CHO + HCHO (f) O + CHO 1. CCl4 2. –78°C 2. Both A and B are secondary radicals. –78°C 2. 2. 1. but the radical may form on either of the two carbon atoms. 87. methoxyethene will react to form a rather stable oxocarbenium ion. relative to the carbocation formed from ethene. O3 . H2O 2.(d) 1. CCl4 Br I Br I 86. will make subsequent reactions with additional molecules of alkene slower. Since there is no difference in relative stability. O3 . 88. The increased stability. it is anticipated that both will form. ether 2. in roughly equal amounts. Me2S 1. H2O H3O+ OH 89. The C=C unit reacts with the radical formed from AIBN to form a carbon radical. I2 . Hg(OAc)2 . Hg(OAc)2 . NaBH4 1. Under acidic conditions. and should have approximately equal stability. Br2 . BH3 . NaBH4 H3O+ OH PBr3 Br OH 90. AIBN A + B Read and understand chapter 25 before attempting 89-96. . NaOH .
–78°C CHO CHO 1. ether 2. Me2S O H + O 95. O3 . H2O2 93.1. –78°C OH O + OH O 94. OH aq. Me2S MeCO3H (MeCO2H is also formed) O O O 1. O3 .3-diol 96. Me2S CHO CHO 91. O3 . 1. NaOH . OsO4 . . 2. KMnO4 . –78°C 2. 2. t-BuOOH OH hexane-2. NaOH OH OH aq. O3 . H2O2 1. BH3 . –78°C 2. 92.
so the stereochemistry of all groups is fixed. which means that it adds from only one face. cis-3. which is a three-membered ring that does not allow rotation. Given that the stereochemistry of the groups is fixed in the alkene.2-difluorocyclohexene (c) (d) 1.it is racemic F (a) Br (b) F Br E-2. and fixed in the bromonium ion. The second bromine adds anti to the first one. 98.5-heptadiene (e) 99.4-dimethyl-3-octene 4-phenyl-1-hexyne .2-dimethylpropyl)-3-nonene 1. anti attack leads to only one stereoisomer.C C H+ cat H+ .4S) . The reaction proceeds via formation of a bromonium ion.9-dibromo-3-methyl-4-(2. The E-alkene has fixed stereochemistry because there is no rotation about the C=C bond. Br Br Br2 (E) (R) (E) Et H Et H Et H Et (S) (S) (S) Br– Et H Et H Et H Et Br (also 3R. H2O/ether O H C C H H2O O C H C H OH C –H+ C H 97.
2-methyl shift OH2 OH2 OH –H+ 100. there is more steric hindrance of boron and the carbon toms than in A.catalytic H+ H2O H+ 1. The reaction of 3. In B. 101. which has the BH2 group on the less substituted carbon atom.3-dimethyl-1-pentene and BH3 leads to two transition states. C H C CH3 OH2 H3C C H C CH3 H3C C H C CH3 . so A leads to the final product. which is the borane shown. A and B. BH2 A BH3 H BH2 B B H2 H H3C C C H+ CH3 H3O+ H3C H2C –H+ C O CH3 OH OH2 H3C 102.
Chapter 25 must be read and understood before attempting the following problems. catalytic H+ OH H+ 1. HBr Br2 BH3 H2/Pd OH2 SOCl2 104.it does not give a major product HCl 105. . Cl H+ + Cl– 1.2-H shift 106. O O H—Br 2 O initiation step O Br2 HO H—Br Br + Br + Br Br Br Br + Br Br a termination step .2-ethyl shift OH2 –H+ 103.H2O . Synthesis Problems.
111. O3 . H+ 110. EtOH EtO 108. 1. 2. B 8 6 4 PPM 2 0 Ph Ph A A 8 6 4 PPM 2 0 Ph OH OH IR is similar for both compounds. NaBH4 CH3CO3H O + CH3CO2H 109. cat. but the proton NMR is simpler and symmetrical for B. H2O/THF OH Spectroscopy Problems.1. Hg(OAc)2 . . –78°C 2. but not for A. Chapter 14 must be read and understood before attempting these problems. H2O2 CO2H CO2H 107.
.5 in diol.8 for HO-CH 4 2 PPM 0 114. and diol will have signal at about 3. 113. but about 1. 3300 cm–1 IR. 1725 cm–1 Chemical shfit differences in the NMR: >2 for CH2 in the ketone. PPM 3 2 OH PPM 1 0 OH O IR.B 3 2 1 0 PPM O B A A 3 2 1 0 O IR is similar for both compounds 112.
2-butanol 116. 1. 4-Methyl-2-pentanol 117.2-Epoxyhexane 118. starting material. C4H8O.5-Dichloropentane. . 1. which is missing in the other bromide 115. 3-(Bromomethyl)pentane 119. which is missing in the other bromide 4 2 PPM 0 This is characterized by a downfield CH2 group of the bromomethyl.no distinguishing signals for either bromide in the IR Br 3 2 PPM 1 0 Br The most distinguishing feature of this product is the methyl group. based on spectral data Br or A 120.
Me2S A O H HCHO 121. O3 . –78°C 2.1. H precursor to A .
and water and methanol are neutral molecules. The circled carbocation is a primary carbocation. but first order reactions are most facile in water and slow in virtually all other solvents. THF Br NaI . which is much less stable than the secondary or tertiary carbocations that constitute the other choices. relative to the transition states for the other choices. and so they may also be circled. Although they are nucleophilic. OH O O H2O H O OH 50.CHAPTER 11 48. Note that diethyl ether and THF are aprotic and will best facilitate second order reactions. THF Br NaI Br Br some SN1 here Br EtOH–H2O KCN . The way the question is worded. the higher concentration of electron density on the anionic methoxide makes it the . EtOH 52. The circled primary bromide is the most reactive because it offers the least amount of steric hindrance in the pentacoordinate SN2 transition state. 53. 49. Br Br Br NaI . 51. There are fewer stabilizing alkyl groups on the primary carbocation. ethanol and formic acid allow second order reactions to proceed faster than water. Methane has no electrons to donate.
and SN2 displacement of the bromide would give an oxonium ion. If ethanol reacts with the oxonium ion. It is more likely that there is simply no reaction at all. This is an SN2 reaction. 2-Phenyloxirane reacts with methanol and an acid catalyst to give an oxonium ion. CH3O– SN1 H2O CH4 CH3OH HSO4– radical addition 54. This is unlikely due to the weak nucleophilicity of water in this reaction. and it proceeds with 100% inversion of configuration at the stereogenic carbon. Water is a weak nucleophile. 56. then ethanol will attack the positive carbon to give the observed product. B. Loss of a proton would then give the alcohol.strongest nucleophile. and the very slow rate of this particular reaction. however. (S) (R) NaCN Br Br Me Me Br Me KI I Me Br 57. attack should be at the less hindered carbon (path a). OEt MAJOR OH OH B Ph Ph + b H O H Ph OH O a Ph b HOEt a HOEt A Ph OEt . Me Me Excessive steric hindrance in the pentacoordinate transition state makes the activation energy for the reaction so high that it does not proceed 58. If the oxonium ion opens to give the carbocation. The hydrogen sulfate anion is a weak nucleophile due to resonance delocalization of the excess electron density. SN2 acid-base 55. but it may open to form the resonance stabilized benzylic carbocation shown.
NEt2 Cl OH (a) Br (R) (b) OSO2CH3 (c) I methanesulfonate of cyclopentanol 2R-bromo-4-phenylhexane cis-2-iodoethylcyclohexane O F (d) Br (e) F F O S (f) Br 3-bromo-3-ethylhexane O O 2-pentanol trifluoromethanesulfonate 4. O O I HO I HO 61. The three-membered ring oxirane is much more strained than the four-membered ring oxetane. (R) (R) (S) (S) Cl 62. 60. There is a high concentration of charge density on oxygen in methoxide. 2S-butanol is converted to 2R-chlorobutane because in proceeds by a SN2 reaction. In the presence of triethylamine and thionyl chloride. which is resonance stabilized by delocalization of the charge density.4-diphenyl-1-bromo-3-heptanone 63. which makes it rather reactive (relatively unstable) when compared to the methanesulfonate anion. Reactions with HI will open both rings. This stabilization of the ion after it leaves contributes to its being a good leaving group. but the greater relief of strain in the oxirane makes that reaction faster than the identical reaction with oxetane.OH2 O H+ O H H2O OH OH -H+ OH OH 59. the C-O bond of the methanesulfonate is longer and . In addition.
one bromide is a relatively normal primary bromide.) Ph I HI KI . 64. H H CH3 I Br I Br Br Br H H CH3 (a) (R) NaN3 .3-dibromo-4. NEt3 2. so the reaction is expected to be slower.4-dimethylpentane. 1-Bromo-2-cyclohexylethane is a “normal” primary alkyl halide. aqueous THF . MeSO2Cl . as is 1-bromo-2-cyclohexyl-2methylpropane. THF (S) Br (b) (R) (R) N3 Ph KI . heat Ph I Br (c) OH 1. In 1. The longer and weaker bond is easier to break.R. aqueous THF . heat Ph Br via rearrangment of the initial 2° cation (1. NaCN .2-ethyl ehift) (f) + O OH 65. the pentacoordinate SN2 transition state for 1-bromo-2-cyclohexyl-2methylpropane is somewhat more sterically crowded that that for 1-bromo-2-cyclohexylethane. contributing to a better leaving group.weaker than the C-O bond of methoxide because the sulfur atom is larger. However. 0°C no reaction (N. THF CN (d) Br (e) Ph Ph NaCN . THF . and the sulfonate group is larger and more electron withdrawing. I 66. which means it will have a longer half-life. but the .
The product of the reaction with diethylamine is an ammonium salt. then it is more difficult to donate electrons to n electrophilic atom. THF is 66°C. The solvent will play an influential role. Diethyl ether has a low boiling point and is easily removed. Et Br H N Et Br N Et H Et Et H + Et C H H Br I Et C + N Br Et H H 71. Ionization is very slow in ethanol. this is a neopentyl bromide unit KI Br Br this is a primary bromide unit Br I 67. so the SN2 process wins.3.2 indicates that the dielectric constant of DMF is 36. but the low dielectric indicates that the reaction will be slower. Increasing the concentration of one of them will allow the rate to increase and the reaction to be completed faster. Table 11. it just may take more work. Note that DMF is a perfectly good solvent and there are methods for separating product from solvent. If the charge is dispersed over several atoms. the transition state has a different charge distribution that the normal SN2 transition state.other is a neopentyl bromide. which separates charges. whereas THF as a solvent does not provide stabilization at all. 70. for all practical purposes water is the only one that can ionize the halide so an SN1 reaction can occur. facilitating isolation of the product. The best choice is probably THF. acetone is 20. Of the solvents used in this book. NaX. DMF is 153°C. as shown. The best solvent for this reaction is DMF. Acetone often contains water and is difficult to dry. Neopentyl bromide is extremely unreactive in SN2 reactions due to excessive steric hindrance in the pentacoordinate SN2 transition state. Since this is an SN2 reaction. 69. Therefore.7 and diethyl ether is 4. In water. Since NaX is the cheap component. THF is 7. acetone is 56°C and diethyl ether is 35°C.6. 68. The nitrate anion (NO3–) is resonance stabilized. which means it is less nucleophilic. . even if the product is isolated by liquid-liquid (column) chromatography. increasing the concentration of NaX to 10 equivalents for one equivalent of RX will diminish the reaction time from 100 hours to 10 hours. the rate depends on the concentration of both RX and the nucleophile. Therefore.7. the reaction with the simple primary bromide is much faster and leads to the major product. so the charge is dispersed. charge separation will accelerate the reaction. The boiling point of 1-iodopentane is 155-157°C . Adding more NaX can adjust the rate further is necessary. but the boiling point is too close to the product for facile separation.
The product is a nitrile generated by reaction of the nucleophilic cyanide with the carbocation. and the aqueous solution slows the SN2 reaction. Iodine is also a better leaving group relative to bromine. whereas reaction at nitrogen generates what is known as an isonitrile. which makes it more stable. 75. so it is more reactive with the azide anion. so the C-Br bond distance is greater than the C-F bond distance. the primary alkyl bromide does not undergo ionization to a primary cation. –CN –CN N C C N Br (R) (S) NaNH2 :– Br 74. The increased stability of the intermediate means that formation of this intermediate is facile. Ionization of 4-phenyl-3-buten-2-ol generates a resonance stabilized carbocation. and the great stability indicates a low activation energy and facile formation. it once again becomes available for reaction with another molecule of the alkyl bromide. Reaction via carbon gives the usual nitrile. The secondary halide is less reactive than the primary halide due to more steric hindrance in the pentacoordinate SN2 transition state. The formal charge on nitrogen in an isonitrile is +1 and the charge on the carbon is –1. 76. Ionization would generate the cycloheptatrienyl cation. When iodide ion is displaced by azide ion. which has four resonance contributors. In addition. This carbocation is very stable due to charge dispersal. In aqueous solution. . 73. with five resonance contributors. the bromide ion is much larger than the fluoride ion. Br CN 79. The charge is delocalized into the benzene ring. so after it leaves there is greater charge dispersal for bromide ion. which accelerates the reaction. Bromine is much larger than fluorine. so it is weaker.O O N O O O N O O O N O 72. The iodide ion is a nucleophile and replaces the bromine atom in an SN2 reaction. 77. which accounts for the rapid reaction in aqueous solution.
which in turn leads to the racemic 2iodobutane. THF KI (S) I . the steric hindrance of the groups attached to C= prevents planarity. and there is a slight distortion from planarity for the C+.OH (Z)-4-phenylbut-3-en-2-ol I + E+Z I OH I 4-phenylbutan-2-ol 80. so the incoming nucleophile approaches from the most open face. THF (S) KI OH (S) aq. OH I aq. If the observation is that 4. The 3D model shows the steric hindrance.2-dimethyl-3-(1-methylethyl)-3S-hexanol undergoes ionization to a cation but gives more of the S-enantiomer than the R. then the carbocation cannot be planar. Ionization of 2S-butanol leads to a planar carbocation. In fact.4-diethyl-2.
but rather proceeds by two different . H OH OH This result implies that the reaction is not ‘pure’ SN1.2-H shift (S) OH (a) +H+ OH2 HCl Cl – H2O + Cl– cat H+ . 83. and after rearrangement via a 1.2-hydride shift. the tertiary carbocation is symmetrical and achiral. In other words. making it a symmetrical molecule. the carbon bearing the iodine atom is not chiral because it also bears two propyl groups. heat Br H _ –Br +I_ H 1. Ionization to the planar carbocation destroys the stereogenic center. when iodide ion reacts to form the product. H2O (b) +H+ O + H2O O OH OH –H+ OH2 82.81. H I H2O–THF (R) (S) achiral KI .
which is the case in this example.2-akyl shift OH –H+ –H2O H2O HO . via ionization to a carbocation. 84. H+ pinacol O HO 1. assume a single mechanism is operative. and product arises by that mechanism should not be influenced by the concentration of the nucleophile. Some of the product must arise by an SN2 mechanism. It is one of those things you should keep in the back of your mind if you actually run an experiment in the lab. there is a tendency to categorize reactions as 100% one thing or another. proceeding by one distinct mechanism. In real life. Some of the reaction occurs by SN1.mechanisms. although for the purposes of doing homework in this book.2-ethyl shift –H+ OH (b) H+ OH HO OH cat. there are reaction conditions and molecules that react by more than one mechanism. in which case an increase in nucleophile concentration will have an influence on the rate. In this book. cyclopropylmethanol H3O+ OH OH cyclobutanol HO (a) H+ HO –H2O OH2 OH cat. H+ pinacol O OH 1.
Therefore. H+ aqueous THF 1. N2+ is a remarkably good leaving group.(c) H+ OH2 –H2O OH cat.2-alkyl shift OH –H+ H2O Demjanov OH2 85. R-N2+ = R-N N+ R+ + N N (nitrogen gas) NH2 N2 (a) 2-aminopentane OH2 OH NH2 (b) 1-amino-2-methylcyclohexane N2 OH2 OH (c) H2N N2 1-amino-2. and in aqueous media some ionization to the carbocation is possible.2-dimethylpropane OH2 OH 86. with some SN1. which is a remarkably stable molecule. Remember that the ammoniums salt is an ion. As with question 83. . there is a mixture of two mechanisms: mostly SN2. This ionization is responsible for the observed stereochemical mixture of products. which facilitates ionization to the carbocation. The products are the carbocation and nitrogen gas.
H2O2 . (a) HBr OH OH Br Cl SOCl2 (b) 1. THF NaN3 . Me 88. B2H6 . No mechanisms are provided.A Me Me Me Me Cl Me Me H+ Me Me H Cl B Me Me Me Me Me Me 87. The major product or products are given. CH3I . THF (c) 2. THF OCH3 (d) Br (e) N3 Cl2 . NaOH 3. NaNH2 4. light Cl (f) OH Br POCl3 Cl KI . H2O-THF I (g) .
THF 0°C no reaction (N. THF-H2O Br HBr NaCN . NaN3 . THF OCH3 N3 1.R. THF CN I (o) CH3 NaN3 . NaCN NC Br (k) OH (l) OH (m) I (n) CH3O–Na+ . H2O THF . THF (r) O N3 OH . I2 Pred 2. THF CN (j) OH cat H+ .(h) Cl NaBr . aqueous THF reflux Br OH (i) cat TsOH O NaCN . heat N3 (q) NaN3 . 200 days NaN3 . THF .) OEt Cl (p) Br NaI . EtOH reflux .
89. The major product or products are given. No mechanisms are provided. (a) Cl
1, KI , THF H2O
I E+Z I
t-BuOOt-Bu 2. NaCN , DMF
CN (c) OH Br
1. 9-BBN , ether 2. H2O2 , NaOH 3. SOCl2 4. K-phthalimide NaH , THF
Br + CH3OH
1, NaH , THF 2. 2S-bromobutane 3. HI
(g) Cl I (h)
1 equivalent NaCN THF
KI , aq. THF
1. NBS , h 2. HC C– Na+, THF 3. NaH , THF 4. CH3I
1. HCO3H 2, NaCN , DMF 3. dilute H3O+ HI
1. CH3CO3H 2. NaI , heat 3. dilute H3O+
90. Radical chlorination of cyclohexane gives only one product because there is only one type of hydrogen. There are twelve hydrogen atoms, but they are all chemically identical, hence, one product. Hexane has three different types of hydrogen atoms: 6 methyl hydrogen atoms and two sets of different methylene atoms. Therefore, there are six identical methyl protons, four identical CH2 protons, and another set of four identical CH2 protons, and radical chlorination gives three different products. Cl
91. The lack of selectivity is due to formation of allylic radicals. There are two different kinds of hydrogen atoms that lead to two different allylic radical. Each radical will lead to bromination at two carbon atoms, but in one case the same bromide is formed. Therefore there are three different products, although in two of the products, they will exist as E and Z isomers, so in reality there are five different products.
92. For 3-methylpentane, there is no great difference in the rate of hydrogen abstraction for the different types of hyrogen atoms. There are four different types of hydrogen atoms, so there are four different products. In the case of 3-phenylpentane, however, one of the hydrogen atoms is benzylic, so formation of the corresponding radical is very fast because of the resonance stability of the radical. Therefore, there is a large rate preference to form the benzylic chloride shown, which is the major product.
Cl Cl Cl Cl
Synthesis. Do not attempt the following until you have read and understood chapter 25.
O (a) OH OH (b) O
1. PBr3 2. Na phthalimide, THF 3. N2H4 NH2 1. PBr3 2. Me2NH 1. PBr3 2. Na phthalimide, THF N
(c) HO Br
1. Na phthalimide, THF 2. N2H4 3. PhCH2Br
1. PBr3 2. CH3CH2CH2CH2O–Na+ THF 1. PBr3 OH 2. NaCN , DMF 1. NaOEt , EtOH 2. Br2 , CCl4 1. HI 2. NaH , THF Br Br O CN
1. HBr (a) 2. NaOEt , THF 1. NaNH2 2. 2-iodobutane 3. NaNH2 4. iodoethane 1. PBr3 2. MeC C:–Na+ , THF 1. PBr3 2. NaCN , DMF OH O (e) N-H O (f) 3. H2 , Pd-C 1. NaNH2 2. EtCH=CHCH2Br , THF 3. N2H4 1. MeCO3H 2. K phthalimide 3. NaH 4. CH3I 4. N2H4 OMe NH2 NH2 O
Spectroscopic problems. Do not attempt these problems until you have read and understood chapter 14. 96.
both C=C units will absorb at about 1650 cm–1 in the IR
2 methyl gorups and 2 alkene H
1 methyl group and 3 alkene H
IR; 2230 cm–1
OH OH IR: 3300 cm–1 for both
unsymmetrical, so a more complicated spectrum. No singlet methyls and there is a CH downfield, adjacent to the OH
the symmetry leads to a simple spectrum that include a singlet methyl. No protons adjacent to O suggestes 3° alcohol
99. N,N-dimethylethanamine, C4H11N 100. 101. 102. 103. 104. Dipropyl ether, C6H14O 4,4-Dimethyl-2-pentyne, C7H12 2-Methyl-butanenitrile, C5H9N 2-Ethyl-2-methyl-1,3-propanediol 2-Bromohexane
aq. H+ 1. NaH B OH 2. CH3I C OCH3
EtOH EtOH. KOH.3.6-tetramethylhept-3-ene non-8-yn-3-ol . 27. making the alkene is more stable. 0°C Br Br Cl 26. The circled alkene has more electron releasing alkyl groups on the C=C. NaOEt 25. NaCl. ether aqueous H2SO4 NaNH2.CHAPTER 12 24. 1° 2° 3° 2° Cl (a) OH CH3 Br (b) (Z)-2-bromohex-2-ene 2-chloro-1-methylcyclopentanol (c) (d) OH 28. NH3 H2O.4. (E)-2. which makes the -bond stronger.
1. which requires severe distortion and is too high in energy to occur in this system. and the alkene product resulting from each. the -carbon is NOT chiral. Although 2S-bromopentane is chiral and has one stereogenic center. EtOH Br 2-bromo-bicyclo[2. Reaction of ethoxide with the -hydrogen atom next to the bromine-bearing carbon will initiate an E2 reaction to give alkene B. Cl– HO– CH3O– I– CH4 Br 31. Formation of a strained four-membered ring is rather difficult due to the higher energy of that strained ring. Remember that formation of the alkoxide is a reversible acid-base reaction. but this reaction would form the 4-membered ring ether (A). and an alternative reaction is possible. KOH . it is likely that under these conditions the alkene (B) is the major product via the E2 reaction. Removal of one of the protons leads to the E isomer. An SN2 displacement of the nearby bromine atom is possible. Elimination to the give alkene away from the bridgehead carbons is less strained. Forming the C=C unit toward the bridgehead demands that those carbon are flattened. . H (E) (S) CH3 H H H3CH2C Br Br (S) H H3CH2C H (S) CH3 H (Z) Br 32. Both products are produced. made of sp2 carbon atoms that are trigonal planar. whereas removal of the other proton leads to the Z isomer. Remember that the C=C unit. The alcohol is more acidic than the -hydrogen. will flatten that region of the molecule. The rotamers for removal of each -proton are shown. so it is reasonable that reaction with ethoxide will generate an alkoxide base.Br Br Br 29. 30. Given the high energy requirements for generation of A and the reversible nature of alkoxide formation.1]hexane major prodct NOT formed requries severe distortion at the bridgehead carbons 33. so either proton may be removed in an E2 reaction.
so it is more stable. the product is more stable. whereas the product of the alkene-acid is an alkene. EtOH H OH NaOEt . . Therefore. In 2-ethylbut-3-enoic acid. and occur under milder conditions. A simplistic idea is that the carbonyl oxygen is more basic than the alkene unit. which also drives the reaction and makes decarboxylation of the dicarboxylic acid more facile (it occurs at a lower temperature). the requisite six-center transition state requires that an alkene unit attack the acidic proton of the carboxyl group. EtOH H Br Br H A OH H B 34. The product of the dicarboxylic acid reaction is an enol. The enol is more stable due to the electron releasing oxygen atoms. so the reaction should be faster. and it will be the major product Br 35. and remember that this enol tautomerizes to the stable carboxylic acid unit. The six-centered transition state of 2-ethylmalonic acid required for decarboxylation effectively has the oxygen of one carbonyl attack the acidic proton of the other. O O O H O H O O H CH3 O CH2 O H H KOH EtOH Br H tetrasubstituted.H O– H O NaOEt .
so no acid-base reaction is possible and E2 cannot occur. which is the one with the least steric crowding. but the counterion is the hydrogen sulfate anion. Br HO Br H H too much steric hindrance. This anion is resonance stabilized and is not very nucleophilic. a pentacoordinate transition state is required. There are no -hydrogen atoms. This restriction means that the lowest energy transition state will lead to product. The hydrogen sulfate anion is basic enough to initiate an E1 reaction via the carbocation. The two possible reactions are E2 and SN2. which leads to cyclohexene.36. and the bulky groups raise the activation energy of that reaction so high that it does not occur. so hydroxide can only remove the bhydrogen atom via an eclipsed rotamer. which leads to the less substituted alkene as the major product. the sulfate ester formed via the SN2 pathway is very unstable and will ionize to form a carbocation. The leaving group (NMe3) is tethered to the base (hydroxide). OH Br H2SO4 HBr 38. For an SN2. HBr reacts with the alcohol to form an oxonium ion. NMe3 Br NMe3 OH Br . In addition. or ionization to a carbocation is followed by reaction with the nucleophilic bromide ion by a SN1 pathway. Therefore. an oxonium in is also formed. which is either displaced by the nucleophilic bromide ion to give the bromide by an SN2 pathway. so it is so high in energy that reaction does not occur Br no -hydrogen atoms so no E2 37. either the SN2 or SN1 pathways are problematic. When sulfuric acid reacts with the alcohol.
Draw the major product expected from each of the following reactions. Br I (a) KI . t-BuOH conc. SOCl2 (c) OH OH (d) I (e) Et (f) Br Me (R) (S) E+Z 2. EtOH Ph Me Br (R) + E+Z Ph Me Et E+Z KOH . t-BuOK . EtOH Br H H Me . so this reaction is slower leads to 3-methyl-1-heptene this is less sterically crowded. EtOH H H (S) H Et H C3H7 Br (S) Ph (g) Me (R) (S) (R) NaOEt . H2SO4 CH3 CH3 CH3 KOH . EtOH E+Z 1.H H3CH2CH2CH2C OH CH3 NMe3 CH3 H3CH2CH2CH2C(Me)HC NMe3 OH H H H leads to 3-methyl-2-heptene this is more sterically H crowded. H O-THF 2 (b) Br NaOEt . H and proceeds faster 39.
If heated for a long time with an excess of base. elimination will occur by removal of the hydrogen on the carbon bearing the bromine.3-dibromopentane will give the more highly substituted alkene because the reaction is under thermodynamic control. to form an alkyne. Elimination to form the alkyne requires removal of the -hydrogen. the vinyl bromide can also undergo elimination. EtOH (E) OH Br (j) H H chloride forms with inversion (E) CHMe2 KOH . EtOH Br Br (k) CHMe2 KOH .Br (h) (R) (R) (R) Me Br (R) KOH . t-BuOH Ph NMe3 OH (m) H Me H 200°C Ph 40. and removing the -hydrogen from a sp2 carbon on a C=C unit is more difficult than removing a -hydrogen from an sp3 carbon. EtOH (E) Me (i) (S) (R) H Me H Cl (S) (S) KOH . the hydrogen atom on an sp3 carbon is more acidic than the hydrogen on an sp2 carbon. EtOH no E2 reaction Me (l) (S) (R) I Ph (R) (S) (R) Br I (R) Me (S) (E) t-BuOK . An E2 reaction with 2. In other words. . Therefore.
This benzylic C+ unit will delocalized the charge into all three benzene rings. A -bond in this molecule requires flattening at the bridgehead carbon. and removal by the base will generate a new C=C bond. H KOH C Br 43. Loss of water from the initial oxonium ion leads to the carbocation. It is noted that this question is more hypothetical. A OH . which is not possible due to the extreme distortion that would be required. The energy barrier imposed by such distortion makes the reaction very difficult. so no elimination 41. but this will also generate an allene. and cannot form. the energy of the alkene product is prohibitively high. and indeed it does not occur. There s only one -hydrogen. and the extensive charge delocalization makes it very stable. Br 42. In other words. and usually requires significantly more heating.Br Br Br Br no -hydrogen atoms. and that formation of allenes this way is not as easy as this reaction suggests because loss of Br from a sp2 carbon is difficult. Ph Ph Ph OH H+ Ph Ph Ph H O H 44.
O O H O HO 46. loss of CO2 would required “dumping” the electrons from the C-C bond on carbon. The enol derived from decarboxylation of B is more stable than the product derived from decarboxylation of A. which tautomerizes to the carboxylic acid. which makes the overall process more facile (occurs at a lower temperature). and the energy demands are too high.4dicarboxylic acids. which can tautomerize to the carboxylic acid. the reaction is much slower and requires much higher reaction temperatures to overcome the high activation energy for reaction. CO2H CO2H A B O 47. but not with 1. The lowest energy eclipsed rotamer will be the one in which the base removes the proton from the less substituted -carbon. the product is an enol. leading to the less substituted alkene. Examining the structure shown for 2-methyl-1. which is a high energy intermediate.45. The base is the oxygen attached to N.3-dicarboxylic acids. but the oxygen of an ester is a significantly weaker base than the hydroxide in used in the Hofmann elimination. . Me O O Me N H N CH3 CH3 H H CH3 + Me2N-OH 48.4-butanedioic acid indicates that if one carbonyl attacked the acidic proton. whereas decarboxylation of A leads to an alkene. For 1.3-dicarboxylic acids. decarboxylation of B leads to an enol. In addition. It is the same mechanism. or than the negative oxygen in the Cope elimination from question 47. and reaction with a -hydrogen atom must occur via an eclipsed rotamer. there is somewhere for the electrons to go with 1. The oxygen atom in B is a stronger base in the reaction with the acidic proton of the COOH unit when compared to the C=C unit. internal acid-base reaction via the lowest energy eclipsed rotamer. as shown. In other words. It would form a carbanion. Therefore.
Br2 . and it is clear that the bromine is in an equatorial position. there is no E2 reaction. HBr A B 2. and those electrons approach the bromine-bearing carbon from the back (180° attack) to displace the bromide leaving group and form the new C=C unit. H Br CH3 CH3 H CH3 CH3 H Br KOH . THF Br heat H O O– OH H Br H O . Therefore. A 1. It is also true that the bicyclic nature of the molecule effectively locks it into the conformation shown. heat B 50. excess t-BuOK t-BuOH . CCL4 2. so it cannot undergo an E2 reaction (no trans axial -hydrogen). Once the alkoxide is formed. KOH . Br OH H H NaH . EtOH 52. EtOH 49. 51. so there is no chance that the bromine can assume an axial position. the orbitals of the bonds are aligned so that transfer of electrons to form the carbonyl will break the adjacent bond.O OCH3 H3C CH3 O MeO H H A CH3 H 1. The actual conformation of the molecule is shown.
Synthesis Problems. NH2 53. Br2 . EtOH 1. NaOH . KOH . EtOH 3. EtOH 3. HBr 2. KOH . 1. HBr 2. PBr3 (c) OH 3. Reagents are provided for each synthesis. KOH . Do not attempt until you have read and understood chapter 25. HBr 2. Ag2O . Do not attempt until you have read and understood chapter 14. EtOH (a) gives E + Z 1. H2O2 1. CCl4 Br Br OH (b) (d) Spectroscopic problems. E2 55. excess MeI 2. 1. BH3 . 200°C 54. KOH . H2O 3. Br minor major . ether 4.
60.5-Dimethyl-1-hexene. 5. Methylcyclopentene OH PBr3 Br KOH EtOH C 61. A B . 1-Methylcyclohexene 59. 0 6 4 PPM 2 0 OCH3 4 2 PPM 57. IR: about 1650 cm–1 NMR: alkene proton and C=C-CH3 NaOMe Br THF IR: no distinguishing peaks NMR: nothing past 3. 5-Methyl-1-hexyne 58.56.6 ppm and a OCH3 singlet.
whereas ionization is very slow in most any other solvent. and the positive H forms a dipole interaction with the negative ion or atom. and once the ions are formed. 3 4 (least stable) 1 (most stable) 2 . there is a + and a – polarized atom. The other solvents are simply not as good as solvation and stabilization. 2-bromo-2-methylbutane is a tertiary halide with a large activation barrier to the sterically hindered pentacoordinate transition state. 20. 15. which helps to stabilize each ion. water facilitates ionization and solvates the ions. An SN2 reaction of the secondary halide 2-bromobutane has a relatively low activation barrier to the pentacoordinate transition state. these interactions cause each ion to be effectively "surrounded" with water (solvation). and the negative oxygen forms a dipole with the positive ion or atom. CH3CH2OH inversion product I (S) (S) (R) (R) Br I Br 16. Since SN1 and E1 proceed by ionization to a carbocation. Water assists in the ionization of compounds via dipole interaction of both the H of water and the oxygen of water. Therefore. No other solvent is as efficient at solvating both cations and anions. These dipole interaction facilitates the ionization. so the SN2 reaction does not proceed.CHAPTER 13 O Cl CCl4 O CH3CH2OCH2CH3 NH3 Me3COH Cl O O CCl4 O CH3CH2OCH2CH3 NH3 DMF H Cl OH OH H2O H OH OH H2O CH3CH2OH 14. CH3O– H2O CH4 CH3OH HSO4– 17. 19. Therefore. best nucleophile 18. However. water facilitates these reactions.
H D E Br 26. No mechanisms are provided.21.2-methyl shift CH3 HOEt CH3 –H+ H H3C O Et 24. EtOH Br (Z) HBr Br racemic Br2 .2-H shift 23. CCl4 (E) (S) one enantiomer KI . . KI . H (R) (S) KOH . heat – Br– Br I + I– 1. 22. H3C CH3 EtOH . reflux 2 weeks H3C OEt –Br– H3C CH3 Br 1. EtOH I C 25. NaOEt increased by 2 H2O decreased by 2 CH4 no effect NaNH2 HNO3 decreased by 10 increased by 10 H2O . THF H A B Br (R) H (R) (R) KOH . The major product or products are shown.
Pred/I2 2. DMF (h) CH3 (S) CN (S) (i) (S) H (j) I (S) (S) NaNH2 . THF OH OH Et I Et Et H (e) (S) (R) Et KOH .(a) Br KI . EtOH KCN .R. PBr3 2. aq. THF (b) Br Ph (c) Me (d) (R) (R) (S) no reaction (N. BuLi . NH3 (E) . aq. benzyl bromide OH CH3 Br (R) 1. EtOH + I Me (R) H I NaH THF Me (R) (R) (S) H H Et O Ph Br Ph OH (f) OH 1. THF I NaCN .) Ph 0°C cat. THF (g) 1-heptyne 2. H+ . MeC C-Na+ C CCH3 Ph 1. NaOEt .
EtOH (Z) I (m) OH 1. THF reflux . aq. 2S-bromopentane (R) (p) (Z) 1. DMF (S) CN (R) Br (r) CH3 (s) H3C (R) (R) KI . THF Br N. 1 month no reaction (N. NaH . heat (R) Br H3C I . MeSO Cl 2 2. with NaI Br (q) NaCN .R.R.Br (k) Br (l) KI . HBr 2. KI . DMF CN Br (n) OH (o) NaOMe THF OMe O 1. NaCN . THF 2. NaI . THF KOH .) CH3 H2O .
65.88% M+1 (84) 5.46% M+1 (97) 7. Cl.03202 66.50 4.62% M+2 (98) 0.04220 %C 18.86 (3. 250.51 7. Formula CClF CH3ClO CF2O C4H2O CH3FO2 C3H2N2 C2H4F2 C 5 H6 C3HNO C2HN3 CH3F2N C4H5N Mass 66. 3 rings or -bonds.10264 67. and 248 + mass based on lowest mass isotopes.83 17.1%).15 C6H12O.89 20.89 62.00581 67.99172 66.00 0.07 18.05 6.37 90.94 Molecular Weight: 94.00 0. C7H12.86 (100.55 0.94 (1.00 0.00 0.00 0.00 0.24 24.00 0.1%) Elemental Analysis: C.19.92 71.16 44.00 %N 0.05928 66.00 0.02180 66.82.00 0.01171 66. 42.00 0. 14.00 0.01056 66. 12.54 36.36 m/z: 249.20 72.98724 65. 2 rings or -bonds. higher mass peaks are 55+35+79+79 = 248 and 55+35+79+81 = 250.10 9.1%).30% M+2 (98) 0.03833 67. 95.66% M+1 (111) 8.53 0.00 28.00 0.02336 67.00 0.85 (13.0%).86 (1.04695 67.0459. 19.00 0.00 56.02811 66.00 %F 28.4%).19 54.73 18.15 1.00 3.3%).42% M+2 (151) 0.83. Cl Br M M+1 M+2 M+4 M+6 248 249 250 252 254 44% 2% 100% 69% 13% based on 75% 35Cl + 25% 37Cl + 2 each of 100% 79Br + 98% 81Br C4+H7 = 55.00 0. 2 rings or -bonds. C5H9N. 252.46240 66. 4 rings or -bonds. 3.32 0. 37+79+79 = 250 37+81+79 = 252. 2.86 Molecular Weight: 250. 253.77 0.1%).00 0.00721 66. Br Chemical Formula: C4H7Br2Cl Exact Mass: 247.48722 66.91% M+2 (102) 0. 55+35+81+81 = 252.00 23.4%).00 0. 251.00 0. H.00 42.01705 67. 37+81+81 = 254 248 250 252 254 .09040 Exact mass 65.94 m/z: 93.CHAPTER 14 41.56 0.00 57.05 4. 1 ring or -bond.86 (4.06 24.34 53. Br.19.95 (1.00 0.04704 67.00 0.59 0.96726 65.86 (44.40 0.9%) Elemental Analysis: C.07 18. H.85 53.00 0.94 (100.46 0.16 94 95 96 43.39% M+2 (85) 0.3%).74 35.50 1.00 0.00 0.00 0.0%).00 0.00 24.00 20.77% M+1 (97) 6.88 %O 0. 84.00 0. 248. (a) M (100) 100% (b) M (149) 100% (c) M (96) 100% (d) M (96) 100% (e) M (110) 100% (f) M(83) 100% M+1 (101) 6.06228 66.00 57.86 0. 2 rings or -bonds.66% M+1 (150) 11.61 %H 0. 63.00 0.00 0.22 48. 94.51 %Br 0.00 4.05057 66. C10H15N.42% M+2 (112) 0.67 20.94 (97.00 %Cl 53.00 0.58 3. Br.68 0. The high resolution mass is measured to be 66.86 (69.00 0.00 0. C6C8O. 247.05004 67. C8H14.00 CH3Br Chemical Formula: CH3Br Exact Mass: 93. 96.
M:M+1 = 100:7. C7H8. Loss of CO2 .054 C2H6N2 (e) 58.0%) Elemental Analysis: C. 0.84.77 triethylamine.03 butanenitrile.0732 and the daughter ion has a mass of 57.0939 C5H12 (d) 58. In a laboratory. 123. if possible. C6H15N. Loss of butyl (d) M = 122. C4H10.45.1%). Loss of 56.0626. then this must be rounded to C22. If there is experimental error. If M+1 = 24.38 m/z: 117.06. Based of the exact mass of the daughter ion. Chemical Formula: CHCl3 Exact Mass: 117. (a) M = 86. Loss of 44. Suggest a cleavage that would lead to that daughter ion.0%). Determine a reasonable empirical formula based on the following exact mass determinations for the molecular ion.0419 C3H6O (f) 58.91 (3. An M:M+1 ratio in a mass spectrum was 100:24.9976.0575 C4H8O (a) 72.91 (1. 89. M:M+1 = 100:6. 120. M:M+1 = 10:4. M:M+1 = 100:4. butane. Loss of water (c) M = 114.0106.0392. M:M+1 = 100:7.0419.91 (100.0211 C3H4O2 (c) 72.91 (30. 118. 119.0341. Loss of ethyl (b) M = 86. always obtain more data to confirm and/or verify a result. 124 118 120 122 124 118 120 122 124 118 120 122 124 49. (b) 72. Cl.91 Molecular Weight: 119. identify the fragment lost from the original molecule.91 (95.1045 and the daughter ion has a mass of 58.9%). Loss of 18.6%). but it is given here for a reason.0732 and the daughter ion has a mass of 68. H. Loss of 29. It shows that sometimes there is experimental error that casts doubt on the real answer.0657 C4H10 50.66 toluene.0626.3%). This is a very ambiguous question.11 = 21.44 2-hexanol.0391.0368 and the daughter ion has a mass of 77. The ratio of M:M+1 for C100H202 = 100:111 47. C4H7N. 121. C6H14O.09 CHCl3 C2HCl3 13CHCl 3 13C2HCl 3 118 120 122 48. then 24/1. 10.6.81 46.92 (1.
Since the C=O unit of the ester has a -bond. If a radical cation formed from naphthalene has the structure shown. Note that . although 2-methylpropanoic acid is also a possibility. so the remainder of the acid is 88-45 = 43. 55.a -electron is most easily removed p p sp2 sp2 electron is likely removed from the -bond s s 51. and more stable. O 53. The high resolution spectrum gave m/z 116. C O O M C O CH3 52. and there is 1 ring or -bond. which corresponds to C3H7. (a) C6H12O2. and dispersal of charge density makes the radical cation lower in energy. this ester is saturated. (b) m/z 29 is C2H5. it is possible to delocalize the charge over the -bonds. 43 is C3H7. The COOH unit of a carboxylic acid corresponding to m/z = 45. A possible structure is butanoic acid. and 71 could be C3H2O2 or C4H6O. An ester gave the mass spectrum shown. resonance delocalization explains the stability of this radical cation. 54. The molecular ion is m/z 88. Therefore.0833.
62. so = 0. and the m/z 91 is loss of propyl. There is a carbonyl peak at about 168 ppm. Structure B does not have an OH group. so = 0.9x105/0. This leaves 6 carbon atoms.159(7.923) = 101. which is loss of methyl.159(5. = (1/2 ) (f/μ) = 0. Loss of an even fragment suggests loss of a neutral molecule. 59.159(5. and the IR spectrum most certainly does: the broad peak between 3200-3600 cm–1.3 x 105 dynes cm-1 for C=O. which as water. This is the structure that is consistent with the IR OH A OCH3 B H O O 60. 58.86. which corresponds to loss of a two carbon unit. 57. which leads to sharp absorption peaks rather than the broad peaks usually associated with OH unit. there is a peak at m/z 92.6 cm–1. there is minimal hydrogen bonding. Note that there are two peaks at about 78 ppm (sorry for the scale). which corresponds to loss of 42 mass units. there are 8 peaks. consistent with an ester carbonyl.159(17. (b) k = 5.159(12.there is a prominent peak at m/z = 60.923) = 87. What infrared absorptions would be expected for each of the following? (a) 1-butyne : 2210 + 3300 cm–1 (b) 2-butyn-1-ol : 2210 + 3300-3500 cm–1 .9 cm–1. (e) k = 12. μ = 12x1/13 = 0.9 x 105 dynes cm-1 for C-H. there is a peak at m/z 119. At very dilute concentrations. structure B fits the NMR.6 x 105 dynes cm-1 for C-C.159(f/μ).31x105/6. which automatically excludes C. and the spectrum is fairly simple. which is more consistent with butanoic acid. (d) k = 17. Structures A-C have 6 or 5 carbons? The peaks at 78 are due to solvent. μ = 12x12/24 = 6.1x105/0.1 x 105 dynes cm-1 for C-H.6x105/6) = 20. so = 0.86) = 28. The telling peaks are at 130 and 138 ppm.1 cm–1. First of all. the more the spring (bond) must vibrate to dissipate that energy.923. Interestingly. suggesting 8 carbons. This latter suggests a McLafferty rearrangement. where μ = (mass1)(mass2) / mass1 + mass2 (a) k = 5.5 cm–1. 56. which are clearly due to a C=C unit. μ = 12x14/26 = 6. For C9H10O. Fragmentation to a radical cation generates a daughter ion with an odd mass. or in this case propene.923. and the more energy that is applied to the spring. so = 0.5 x 105 dynes cm-1 for C N.7 cm–1. μ = 12x1/13 = 0. μ = 12x16/28 = 6. Therefore.5x105/26) = 10. Yes! The energy is transferred to the masses (atoms) at each end of the spring (bond). O A O O B O C O O 61. so a reasonable guess is 5-nonanone for the structure. each of the two O-H bonds can be seen. so = 0.46. (c) k = 7. At very dilute concentrations.
Possible structures are given. NMR: cyclopentane has only methylene groups. and the aldehyde signal at about 9-10 ppm. 2817 + 1730 + 1650 cm–1. C=C at 1650 cm–11. IR. (a) methylenecyclopentane and methylcyclopentene. Other possibilities must include the given functional group. but there are many structural possibilities as long no other functional groups are incorporated. 1725 cm–1for cyclopentanone vs.8-5. a methyl group. but pen-3-enal has the alkene protons at about 4. IR.(c) 1. Br (a) C4H9Br CN (b) C12H11N O O (c) C4H8O2 . one alkene H for methylcyclopentene + a singlet methyl (b) cyclopentanone and pent-3-enal. NMR: 2 alkene H for methylene cyclopentane vs.5 ppm.2-dichloroethyne: 2210 cm–1 (d) 3-cyanobutanoic acid: 2240 + 2500-3000 + 1730 cm–1 63. 64.
The quartet at 4. This is an unsymmetrical ketone. 1552. x =1552.5 Hz. so one methylene is closer to the . A is very symmetrical. so this compound is probably an aldehyde or ketone. only the Cl remains. to be weak.83 ppm.4 ppm (ratio of 2:3). (345)/x = 60/270. 66. which normally resonante past 200 ppm. The molecule is ethyl chloroacetate. and the CH2 unit is either attached to Cl or O. and if we have ClCH2. It is not uncommon for carbonyl carbons.5/270x106 = 5. accounting for seeing only two carbon peaks. 1575/270x106 = 5. and the peak at about 14 ppm is a methyl. as are the other four carbons. If we add up all the fragments. This is an ethyl group. x = (350)(270)/60. The IR suggests a carbonyl. so the structure must be OCH2CH3. The carbonyl carbon is not apparent (note the peaks at 78 ppm are due to solvent). and it is downfield at about 4 ppm. The downfield shift of the OCH2 is due to the electron withdrawing effects of the ClCH2 group. (350)/x = 60/270. so these are not cyclic compounds and there are no C=C units. The CH2 is connected to both a Cl and a C=O. The peak in the IR suggests a carbonyl. so it is further downfield. The other peak in the NMR is a singlet worth 2H. x =1575 Hz. 3450/600x106 = 5. The symmetry in the NMR spectrum suggests this is 3-pentanone. and there is only one oxygen. x = (345)(600)/60. 67. x =3450 Hz.83 ppm. (345)/x = 60/600. which is accounted for by the C=O unit. x = (350)(600)/60.75 ppm. x = (345)(270)/60.NH2 O (d) C3H7NO O (e) C5H10O 65.3 pm is linked to the triplet at 1. If attached to Cl. x =3500 Hz. and one is more downfield than the other. the then structure of the molecule must be ClCH2CO2CH2CH3. or COOCH2CH3. the structure is chloroethane. which does not use up all the atoms. so it is likely this is an ester. There are two different methyl groups and two different methylene carbons. The carbonyl carbon is apparent in B at about 210 ppm. and the other is probably a CH2.75 ppm. 3500/600x106 = 5. The formula suggests 1 ring or -bond. (350)/x = 60/600.
A peak at m/z = 179 relative to a parent ion at m/z = 208 indicates loss of 9 mass units. 2:6 or 3:9. the methyl group in each chair will have a different environment (one axial and one equatorial) so they will have different chemical shifts. all structures that have an ethyl group should be circled.1 ppm (integrates to 3 H) and a singlet at 3. the likely structure for B is 2-pentanone. Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl . CH3 CH3 H H H CH3 CH3 H H3C 70. and only 1. the equilibration is rapid. Therefore. The predicted chemical shift and multiplicity for each molecule is shown.2-dimethyl ethanoate 1. F Cl Br OH 71. and they coalesce into one signal (the average of the two separate signals). A = 3-pentanone. There is only one. A M+2 = 98% of M indicates the presence of bromine.8 pm (integrates to 1 H) indicates that the ratio is 1:3.25 2. and the two different methyl signals are effectively in equilibrium. which corresponds to an ethyl group.1-dimethyethyl ethanoate fits this data.2 (3H) (1H) doublet at 1. methyl 2. 68. This difference can be seen in the proton NMR. so there are two signals.9 (9H) O singlet at at 2.1-dimethylethyl ethanoate O O singlet at 3. below the activation barrier for conversion of one chair to the other. Given this information. A spectrum with a singlet at 1.carbon than the other. B 2-pentanone. At low temperatures. This methyl group is attached to a cyclohexane. At higher temperatures.1 (6H) 69. At low temperatures.5 (3H) O multiplet singlet at 0. both chair conformations will exist. and the molecule exists in two equilibrating chair conformations.
The choice can be made solely on chemical shift. The IR data indicates the presence of an aldehyde. OF the other cases. . the signal at 5. (a) How many different signals will appear in the proton NMR spectrum of A? 2 different signals. so any structure that does NOT have a CH should be circled. The circled compound also has the quartet:triplet characteristic of an ethyl group. OH O O O H H O 74. which is why there appears to be only one ethyl group. only the circled compound fits. Of these. H3C Br O O CH3 Br Br Br H3C CH3 Cl3C CCl3 H3C CH3 O A O B H O O 76. only one has an ethyl group.5 ppm.9 ppm as well as a triplet at 1.5 ppm.9 ppm suggests proximity to two functional groups because there are no -bonds in the choices. there are two. one for the CH2 and one for the identical tert-butyl groups.0 ppm and a quartet at 3. Therefore. and that one also has a single methyl that should appear at about 3. A singlet at 5. Peaks at 2850-2960 cm-1 in the infrared indicate C-H. the two aldehydes circled are possibilities. H O O CH3 73.72. Based on chemical shift. The molecule is symmetrical. Any molecule that has a -bond will exhibit magnetic anisotropy in the proton NMR spectrum. but the multiplicity of all but the circled compound does not fit the given data. O s t t t q O s t O s O q O t s t t O q O t s t m OH s m t 75.
the H of the alcohol H–C–O appears about 3. each integrating for 9H. but it will only integrate to 1H.5 and will integrate for 2H. Water will damage salt plates. The circled compounds have no aromatic CH. (c) In A.5 ppm because there is no anisotropy (no -bonds). 77. Note that 3-pentanone has no benzene rings at all. In ethers. and the two tert-butyl groups will likely give slightly different signals. integrating for 18H. so it clearly does not have aromatic CH. In an alcohol.2-3. whereas they may be two slightly different singlets in B. but there is the inductive effect caused by proximity to the electron withdrawing oxygen atom. acetone THF hexane 79.4 ppm in the proton NMR spectrum whereas the proton for ethyne absorbs about 2. Both questions are answered by comparison of the anisotropy diagrams shown. Since only one effect is operative. the chemical shift of the CH2 will be about 3-3. The two tert-butyl groups in A will show up as one singlet. ethene formaldehyde ethyne H H H H H H H O C C H Ho Ho Ho . The most distinguishing feature is the aldehyde proton in B. (b) The aldehyde H–C=O unit appears at about 9.7 ppm) due to the presence of the carbon group. the protons are oriented in the deshielding portion of the anisotropy field and are downfield. the signal is not as far downfield as noted for the aldehyde. Cl CH3 Cl Cl Cl Cl Cl Cl H3C Cl CH3 O Cl 78. so water or any solvent that contains water should be avoided. one for the aldehyde proton.4 ppm because the signal is pushed down field by two factors: inductive effects of the carbonyl deshield the proton. so no peaks in that region indicate there are no aromatic CH. one for the CH group. whereas the CH in B will be slightly further downfield (about 3. although they will have very similar. H2O CCl4 aq. Peaks in the 7-8 ppm region of a proton NMR spectrum indicate the presence of aromatic CH. and the anisotropy of the p-bond also deshield.(b) How many different signals will appear in the proton NMR spectrum of B? 4 different signals. if not overlapping signals. The combination of these two effects pushes the aldehyde proton far downfield. which is missing in A. (a) Ethene absorbs at about 5.3 because the two p-bonds in the alkyne orient the secondary magnetic field such that the protons of ethyne are in the shielding porting of the anisotropy field. and are upfield.
104 107 106 105 86. The molecular ion of C5H9Cl is based on the lowest mass isotopes. In mass spectrometry. ketone aldehyde alcohol ether 2 3 4 5 6 7 8 9 10 1° amine acid 2° amine alkyne 3° amine alkene nitrile alkane 84.1.4 microns is consistent with a triple bond. 700 cm-1 1000 cm-1 1800 cm-1 3200 cm-1 85. and a peak at m/z 84 corresponds to 101-84 = 17. there are CH. The molecular ion for CH3(CH2)5NH2 is 101. not 35.45. shorter frequency (cm) corresponds to higher energy. Referring to Figure 14. both will show a carbonyl at about 1725 cm–1 so mass spectrometry is the best way to distinguish these compounds. Atomic Cl is 75:26 mixture of 35Cl and 37Cl. and the peak at about 4. and this usually means exchanging protons for deuterium in the solvent. Analysis of the molecular ion of each compound should allow them to be distinguished. A solvent that has protons cannot be used in proton NMR because those signals will appear and either “swamp out” signals for the sample. for 12C. The unit in infrared is cm–1. and that of methyl butanoate is 102 due to the extra oxygen atom. 9 for H and 35 for Cl). a primary amine may lose ammonia. 1H 13C 34S 35Cl 81Br 3H 83. CH3OH D2O CH2Cl2 CCl4 CDCl3 81. not the mass from the periodic table.2-Dimethyl-1-propanol 82. By analogy with an alcohol. which gives 35.0003 cm) is higher in energy than 180 cm–1 (corresponds to 0. This corresponds to m/z 104 (60 for C. 0 1 2 HO 3 4 5 6 2. or obscure signals from the sample.45 for the mass. In the IR.0005 cm). Only solvents with no protons may be used. which is the mass of all isotopes based on their natural abundance. 87. so 3200 cm–1 (corresponds to 0. Use the isotope masses. possible functional groups include the nitrile with a C N and an alkyne with a C C.80. . or 1/cm. The mass of 3-pentanone is 86. Therefore. use 35. 1H and 35Cl. which is the m/z for ammonia (NH3). Based on this simplistic figure.
93.5 ppm.4-Dimethyl-3-pentanone. so the chemical shift will be downfield of OCH3.2-Eimethylcyclopentene . 92. Compounds such as this have NO protons at all. the methylene protons are proximal to both a Cl and an O.88. 3-Phenyl-3-pentanol. In the case of ClCH2OCH2Cl. 95. 94. a hydrogen atom on a benzene ring. so any molecule that has a signal downfield of that should be circled.N-diethylpropanamine. 96. This will include anything with a C=CH. 91. 99. 97. 2. N. Ethyl 4-methylbenzoate Diphenylethyne N-Isopropyl-2-methylpentanamide 2-Ethylhexanoyl chloride 1. Diethyl ketal of 2-butanone. An OCH3 signal will appear at about 3. Cyclopentenone. Protons adjacent to a nitrogen atom are upfield of the OCH3 signal. Cl O O Cl N CH3 N 89. a carboxylic acid COOH or and aldehyde H. Cl Cl Cl Br Br Br Br H3C H3C CH3 CH3 Cl3C O CCl3 H3C O CH3 Cl Cl Cl 90. 98.
Chapter 15 26. (a) (b) MgBr MgBr Et2NH NH2 NH + Et2N–MgBr+ + NH–MgBr+ N–MgBr+ (c) MgBr + (d) MgBr OH + O–MgBr+ (e) MgBr + :–MgBr+ (f) MgBr NH + N–MgBr+ . MgBr (a) MgI (b) (c) MgBr Li (a) Li (b) (c) Li Li (a) Li (b) (c) Li Ph (d) CH3Li Ph (d) Li (d) Ph MgBr 27. 29. 28.
The compound that is circled is the only allylic bromide among the choices given. Only allylic and benzylic halides give good yields in this reaction.Br (g) MgBr + MgBr2 (h) MgBr I no reaction (perhaps some elimination to 2-methylpropene) 30. . Li (a) Li (b) Li (c) Li (d) Li (e) + :–Li+ OH + O–Li+ NH + N–Li+ NH2 + NH–Li+ Et2NH + Et2N–Li+ Li (f) NH + N–Li+ Li (g) Li (h) I Br + LiBr Li + LiI 31.
CuI/THF/–10°C 2.2. (j) n-butyllithium + 1. ether –10°C CH3 (b) I Me2CuLi . benzyl bromide. Mg/THF 2. (k) n-butyllithium + N-methyl-1-aminopentane. 2.. (e) 3-bromocyclopentene + 1. . (h) 1-iodopentane + 1. 2-iodo-2-methylpentane. Draw the final product. (g) 2-methylhexylmagnesium bromide + 1. acetylene (b) phenylmagnesium bromide + 1. Mg/ether 2. Mg/THF 2.Br Br Br Br Br (a) Me2CuLi . 33. 1-propyne 2. 2-Propanol has an acidic OH unit.2-dimethoxyethane. 1-butyne. pentane + HC CMgBr 2-phenylpentane 2-methyl-2-butene butene + EtC CMgBr 3-benzylcyclopentene butane no reaction probably no reaction since a 3° RLi is less stable than a 1° RLi 2-phenylhexane 1-propyne + benzene N-methyl-1-aminopentane amide + butane no reaction 34. (c) 2-bromo-2-butene + 1. 2-bromopentane. (l) methyllithum + 1. (d) 2-bromo-2-butene + 1. dilute aqueous acid. ether –10°C CH3 (c) I Me2CuLi . Li 2. for each of the following reactions. (f) butylmagnesium chloride + water. ether –10°C CH3 32. Li/THF 2. (a) 2-iodopentane + 1. and this proton will react as an acid in the presence of the Grignard reagent. if any. 2-bromohexane.4-tetramethylhexane. which is a powerful base. CuI/THF/–10•C 3. (i) phenyllithium + 1. iodomethane.4. CuBr/THF/–10°C 2.
39. Ph2CuLi MgCl Br (b) (d) (e) 37. Remember that organolithium reagents react with both water and air. BH3 . and after formation of the Grignard reagent. Although 2S-bromohexane is chiral.35. and has better coordination with the Mg of the Grignard reagent. CuI 4. HBr 2. 38. The point of this problem is to emphasize that a Grignard reagent formed from a chiral halides will almost always be racemic. which means that they react with oxygen in the air and with moisture in the air. h 2. the THF is better Lewis base. Li 3. the Grignard reagent is configurationally unstable. CuBr 2. SOCl2 2. H2O2 3. 3-methylheptane. Li 3. Vinyl Grignard reagents are less stable and they are more difficult to form because a C=C-X bond is stronger than a C-C-X bond (sp2 vs. and it provides more coordination with the halide which assists in the Mg insertion. ether 1. Reaction with CuBr forms a magnesium cuprate that reacts with iodoethane to give the product. EtI 36. Based on the results. NBS . THF is a stronger Lewis base when compared to diethyl ether. The positive head pressure of nitrogen excludes air and moisture from the reaction.. Br (S) Mg . despite the fact that the starting bromide was chiral. NaOH . PBr3 4. This alkane product is racemic because the Grignard reagent it is derived from is racemic. which helps to stabilize that product. HBr 1. MeI OH 1. The temperature is from –78°C 0°C because at . 1-bromopentane (c) 1. so it will revert to a racemic mixture. CuI 4. Both are pyrophoric. sp3 for carbon). NaNH2 2. ether 2. ether MgBr 1. tert-butyllithium is much more reactive than butyllithium. 1. 1-iodobutane (a) 3. upon reaction with Mg. Mg .
leads to an SN2 reaction of the alkyne anion nucleophile with the allyl bromide to give oct-1-en-4-yne.7 ppm. IR cannot be used alone to see if bromododecane was converted to dodecane because the C-Br unit does not have a distinguishing peak that is easily detected. proton NMR can be used exclusively as a diagnostic tool to distinguish the bromoalkane from the alkane. Therefore. The bromide starting material and the hydrocarbon product have different masses. and the internal alkyne unit of both molecules will show a peak around 2220 cm–1. Amines are very weak acids. The butyllithium is prepared by reaction of the halobutane and lithium metal. the bromide will have a M+2 peak in the mass spectrum that is near 100% of the molecular ion. . and increasing the temperature raises the rate of the reaction. Subsequent addition of allyl bromide. This coupling reaction is known as the Wurtz reaction.7 ppm. and the octane is a hydrocarbon so it is not removed from the reaction mixture. Proton NMR maybe used because the chemical shift of the CH2Br signal of the bromide will be downfield relative to the signal in the alkyne with an alkyl substituent. Do not attempt these until after you have studied chapter 14. In addition. 41. and as the butyllithium is formed there is a competition between reaction of halobutane with lithium metal and reaction with the newly formed butyllithium to give octane. Octane is formed by reaction of butyllithium with unreacted 1-bromobutane (or 1-iodobutane).2. 40. Br CH2CH3 Et2CuLi 43. IR cannot be used alone because the C-Br unit does not have a distinguishing peak that is easily detected. Therefore. Addition of 1-pentyne to the LDA solution should generate the lithium alkyne anion of 1-pentyne along with diisopropylamine. Proton NMR maybe used because the chemical shift of the CH2Br signal of the bromide will be downfield at about 3.the lower temperature the reaction with an amine maybe very slow. and the hydrocarbon product will not. 2. so the molecular ion can be used to distinguish the two molecules. 42.5-Trimethylhexane. whereas in the alkane no signal will be downfield of 1. Spectroscopy Problems.5-1. It is faster at the higher temperature. these is nothing to check.
There is less steric hindrance about the carbonyl carbon in an aldehyde than with a ketone.Chapter 16 27.3-tetramethyl-5methylenecyclohexane 3-ethyl-2-propylpent-2-enal 3-phenyl-2-triphenylmethyl-1-pentene . O (a) 1-cyclopropyl-1-pentanone (b) O 3-ethenylcyclopentanone OHC (c) Cl 8-chloro-5.4. 29.3.5-dimethyloct-3Z-enal (d) O (e) CHO 3.1.5-trimethylcyclohexanecarboxyaldehyde 4. so butanal should be more reactive in acyl addition reactions when compared with 2-butanone.5-dicyclopentylnon-6-yn-2-one (g) (f) 2-cyclohexylcyclohexanone O (h) OHC 6-phenylhex-5-ynal O 6-(3.3-dimethylbutyl)octadecane-3-one 28. CHO Ph (a) (b) (c) Ph Ph Ph 1.
Intramolecular hydrogen bonding in 2-hydroxybutanoic acid weakens the O-H bond of the acid.CHO (d) Br (Z)-6-bromo-2. The hydroxyl group in 4-hydroxybutanoic acid is too far away for effective . 31. 1. O (a) CO2H 5-oxohexanoic acid O (b) CHO 6-oxoheptanal (c) H 6-oxohexanoic acid CO2H O O (a) dibutyl ketone nonan-5-one O (b) O (c) methyl ethyl ketone butan-2-one O O ethyl vinyl ketone pent-1-en-3-one (d) (f) phenyl propyl ketone 1-phenylbutan-1-one dibenzyl ketone 32. so it is named as a cyclopropane derivative.5-dimethyl-3-(1phenylpropyl)hexanal (e) 2-butyl-7-ethyl-5.5-dimethylnon-8-ynal 1-cyclopentylethanone 2.3-diphenylpropan-2-one 33.2-dichlorocyclopentanecarbaldehyde 8-chloro-3. The substituent does not have more carbon atoms than the ring.4-dimethylcyclooct-3-enone 30. and the name is 1-propylcyclopropane carboxaldehyde. making it more acidic.2-dimethylhex-5-enal Cl Cl O (f) (g) Cl O H (h) H O CHO O (i) Ph 4.
The tetrahedral intermediate is the same for both reactions. CH3 – O N O EtO O CH3 EtO– CH3 CH3 N N OEt CH3 CH3 37.hydrogen bonding.3-dimethylhexadecanoic acid . CO2H (a) CO2H 3. There is a great deal of steric hindrance around the carbonyl carbon in 3.3-dimethylheptanoic acid CO2H (d) 1-phenylcyclohexanecarboxylic acid (e) (b) Ph (c) HO2C adipic acid CO2H CO2H 3-methyl-2-(1. the ester is converted to the amide.1-dimethylpropyl)heptanoic acid 7. 35. and makes it less reactive in acyl addition reactions when compared to the unhindered 4-heptanone. O O H O O H O H O H O S CH3C C:– HS C CCH3 34.11. but the amide is NOT converted to the ester.5. ethoxide is a better leaving group relative to the amide anion. Once formed.12-triethyl-2. Imagine a five-membered ring being formed for hydrogen bonding in the 2-hydroxy versus a 7-membered ring for 4-hydroxy.5-tetraethyl-4-that hinders approach of a nucleophile. O O 36.3. For this reason.
38.3. whereas reaction with iodide will generate the weaker C-I bond. Reaction with the ketone will generate a C-C bond. If iodide is a better leaving group. making the reaction reversible. The alkyne anion is a better nucleophile. 41. The alkoxide intermediate from reaction with iodide should easily expel iodide because it is a good leaving group.3-trimethylbutanamide O (g) O (h) 2-butylheptanoyl chloride N. because it is a larger atom (weakens the C-X bond) and the larger iodide ion has greater charge dispersal. O (a) O butyric isobutyric anhydride O O (d) N (e) O (b) O O butyl 2.3-dimethylbutanoate Cl (f) N (c) O O isopropyl isobutyrate O N-ethyl-N. then butanoyl iodide should be much more reactive than butanoyl chloride. O (a) N O N.3-dimethylhexanoate . which is quite strong. These combine to make the alkyne anion a much better nucleophile.3-diphenylpentanoyl chloride Ph Ph (l) Cl Cl O propionic anhydride O 4-chlorobutanoyl chloride 39. Iodide is a better leaving group than chloride.N.3-trimethylbutanamide O O methyl decanoate NH2 (i) O cyclohexyl acetate (j) O O 2-cyclooctylpropanamide Cl (k) O 3. It is! 40.N-diphenylhexanamide (b) O cyclobutyl 3.
dilute H3O+ NaCl no reaction (N.4-diphenyldodecanamide O 4-phenyl-3-cyclohexenyl pentanoate 42. H3O+ (b) O CHO (c) 1. No mechanisms are provided. PhMgBr (e) 2. dilute H3O+ 1. HC C:–Na+ 2. OH (a) CHO 1.R.) CH3 OH HO CN (d) O 1.O Cl hexadec-5Z-enoyl chloride (e) O (g) O butyl butanoate (h) N H O O O ethyl oct-4-ynoate O (c) O O (d) dipentanoic anhydride O (f) Cl N H N-chlorobutanamide (i) O N-cyclopropyl-4. The product or products are shown. KCN 2. MeLi O 2. H3O+ HO Ph .
O (f) H+ forms oxocarbenium ion. BuLi 2. but no other products O (g) H (h) CO2Et O (i) Cl CHO (j) 1. O O BuLi OMe Bu . and it will compete for reaction with the butyllithium. What is not obvious from this chapter. is that the ketone is more reactive than the ester. H3O+ HNEt2 heat NaOMe O O OH CH3 H NEt2 OMe 1. acyl substitution will lead to the ketone. Since n-butyllithium is a good nucleophile. MeMgBr 2. H3O+ HO Bu (k) CO2H CH3MgBr + CH4 CO2–MgBr+ H2O CHO MeLi (l) CHO + CH4 43.
In A. and is more stable. Based on the stability of these conjugate bases. H H O O O H O H O H O O O . O O H A OH O OH H HO O OH B 46. The oxocarbenium ion from 3-pentanone has two resonance contributors.44. whereas the carboxyl groups are too far apart for such hydrogen bonding. intramolecular hydrogen bonding is possible that enhances the acidity. the ester is more basic. whereas the oxocarbenium ion from methyl pentanoate has three. O O O O O O 45.
56.47. The oxocarbenium in is a very strong acid. 54. Protonation of the carbonyl oxygen is reversible. 51. so Ka for this reaction expected to be much smaller than 1. You should read and understand chapter 14 before attempting these 2-Methylpentanal 1-Phenyl-1-pentanone N. which means it is very reactive and the equilibrium for this reaction lies to the left. problems.2-Dimethylpropanoic acid. 55. 58. 4-Penteneoic acid Hex-2-enal 3-Hexenoic acid Hexanoyl chloride Isobutyric anhydride . 53. 49. 52. 57. HO3S H O O –O 3S 48. 50.N-Dimethylbutanamide 2-Pentanone 2. O H O H O H O H O H SYNTHESIS There are no synthesis problems associated with this chapter SPECTROSCOPY.
HCl . the reaction is slower. Therefore. H2O 2. 31. Hg(OAc)2 . OH OCrO3H OH (a) OCrO3H 1. aq. EtOH .chapter 17 oxidation (a) OH Br (c) reduction (d) OMe oxidation (e) CHO (f) CHO oxidation Br oxidation OH (b) NMe reduction NMe 30. NEt3 OH (b) O OEt 1. acetone CH2Cl2 O H (c) OH 32.3-dimethyl-2-pentanol is more sterically hindered. SOCl2 3. NaBH4 3. CrO3 . N H Cr2O7 2 -2 O . The chromate ester derived from 3. acetone 2. and it is more difficult to remove the proton from the adjacent carbon. K2Cr2O7 . aq.
cycloheptanone. H2O2 3. The major products are: (a) 4. (c) cycloheptanol + (COCl)2/DMSO/-78°C. CrO3 . and then adding this mixture to dichloromethane. PhMgBr . HCl . PDC Ph O 33. PCC O (e) OH (f) H O CrO3 . (b) cyclohexanemethanol + oxalyl chloride and DMSO at –60°C. Br OH Br O– oxidation O .(d) 1. It is not completely obvious from the discussion in the book. NaOH . Excess ozone will react with both C=C units. CO2H CO2H HO2C CO2H HO2C CO2H 37. acetone O 1. 9-BBN 2. 4. HCl N CrO3Cl– N H 35.4-diphenyl-1-hexanol + CrO3 and aqueous sulfuric acid in acetone. and the HCl reacts to form a chlorochromate. They are different. 36. aq. and isolating the precipitate. Collins reagent is formed by mixing chromium trioxide in pyridine. but certainly related. THF 2. 34. hydrolysis 3. PCC is isolated as an orange solid by mixing chromium trioxide in aqueous HCl. although at least some of the cleavage from only one C=C is likely.4-diphenylhexanoic acid. aq. Workup with hydrogen peroxide will generate the carboxylic acids. cyclohexanecarboxyaldehyde. It is likely that the Collins regent is more complex since the equilibrium is different in pyridine than in water.
the -bond is more electron rich. acetone H2SO4 40. KOH . Na2Cr2O7 . The reaction with the peroxy acid is driven by electron donation from the -bond to the electrophilic oxygen of the peroxyacid. NaOH . The more substituted the alkene. CH2Cl2 1.38. The trifluoroacetyl group is electron withdrawing.H(OAc)2 . the faster the reaction is expected to be. 3. thenhydrolysis CHO (f) O 39. H2O 2. EtOH 3.3-dipolar reaction.) CHO CHO (c) 2. NaBH4. HIO4 1. the more highly substituted alkene is the more reactive. Me2S (d) CHO + O (e) 1. HBr 2. t-BuOH no reaction (N. Alkyl groups are electron releasing with respect to the -bond of an alkene. The reaction occurs by electron donation from the -bond to ozone in a 1. PCC . Therefore. . BH3 . which makes the electrophilic oxygen of the peroxyacid more positive via inductive effects. ether 2. 41. The more positive the oxygen. OH (a) OH N H CrO3Cl– O CH2Cl2 N H (b) CrO3Cl– CH2Cl2 1. OsO4 . –78°C 4. the more reactive will be the peroxyacid. The more electron rich the -bond. Since a tetrasubstituted alkene has more electron releasing alkyl group.4-dimethyl-3hexene undergoes epoxidation faster than does 3-hexene. O3 . the higher the electron density available for donation in the -bond. and 3. H2O2 3.R. and it reacts faster. aq.
Me2S O CHO (b) + O (c) dilute KMnO4 H2O . NaOH OH OH 44. –H+ H OH O OH (a) CrO3 . –78°C 2. H2SO4 OH H2O . O3 . acetone 1. CH2Cl2 OH H O H+ O H H H OH 43. . OH PCC .O O H OH OH OH OH2 42.
200°C 5. Pb(OAc)4 . ether 3. PBr3 4. H2O 1. pyridinium dichromate CH2Cl2 1. MeMgBr 2. ether 2. H2O2 4. BH3 . H2O2 3. Me2S 1. peroxyacetic acid OH Synthesis. PBr3 2. 1. EtOH . OsO4 . t-BuOOH OH OH . (a) OsO4 . –78°C 6. heat OHC O CHO (e) (f) O 3. Ag2O 4. NaOH . O3 . Do not attempt these problems until you have read and understood chapter 25. KOH . NaOH . –78°C 6. NaOH . t-BuOOH . NaOH . 9-BBN . PCC . O3 .Br (d) 1. H3O+ O 3. NMe3+ –OH 1. O OH 46. Me2S O O 45. 200°C 2. Me3N 3. t-BuOH 3. CH2Cl2 CHO 47. KOH 5. PBr3 2. 48. EtOH 2.
–78°C 4. KOH . O 51. As the epoxide is formed. such as sodium acetate. which can rearrange to a more stable oxocarbenium ion. 2-pentanone. which tautomerizes to the product. the trifluoroacetic acid product is buffered. O3 . By adding a buffer to the reaction. the more stable secondary vinyl carbocation is formed. PBr3 2. which reacts with water to form an oxonium ion. HBr OMe Br (d) Spectroscopic problems. NaNH2 2. Loss of a proton gives the enol. EtI 3. which is a very strong acid. Me2S CHO CHO (c) 1. . NaBH4 1. The second product of the epoxidation is trifluoroacetic acid. it reacts with the trifluoroacetic acid to generate a carbocation. which means that acidcatalyzed processes are minimized. Hg(OAc)2 MeOH 2.OH (b) 1. Loss of a proton lead to the observed ketone. EtOH 3. PPM 1 0 6 4 PPM 2 0 50. Do not attempt these problems until you have read and understood chapter 14 O IR: cyclohexane hs a C=O at about 1725 cm–1 but the conjugated C=O appears at about 1695 cm–1 O 3 2 49. In the presence of the mercuric salts.
which is missing from the ketone. .3 ppm. In the NMR. In the IR.2 ppm that is missing from the aldehyde. both will have a carbonyl peak at about 1725 cm–1. In the NMR.4-diethylhexan-3-one F3CCO3H O 3.4-diethylhex-3-ene + F3CCO2H O HO O O H OH 52. the alcohol will have the broad peak at about 3300 cm–1. but the aldehyde will also have the aldehyde proton signal at 2817 cm–1. the ketone will have a single methyl signal at about 2.4. In the IR. and this peak will disappear as it is oxidized to the conjugated ketone. which will have a carbonyl peak at about 1695 cm–1. Both of the molecules will have alkene protons and an ethyl group. The methyl group adjacent to the alcohol-bearing carbon will be a doublet. OH O PDC hex-3-en-2-ol 6 4 PPM 2 0 8 6 4 PPM 2 0 53. The ketone will have a singlet methyl signal at about 2. the aldehyde will have the signal at 9-10 ppm. The alcohol will have a C=C peak at about 1650 cm–1.
but in the NMR. and the electron withdrawing effect of the oxygen leads to greater deshielding relative to the non-polarized alkene.3-butanediol will show a doublet for the methyl groups. 57. which diminishes the effects due to the proximity of the electron pairs on oxygen relative to the hydrogen atoms. but at 12 ppm for the acid. The result is greater shielding.4-butanediol has no methyl groups. The strain causes the bonds to “bow” from linearity between the nuclei. the most obvious difference is the singlet at 9-10 ppm for the aldehyde. whereas 1. In the IR. . There will be few differences in the IR.O H O 3-phenyl-1-pentanal 3-phenyl-2-pentanone 10 5 PPM 0 8 6 4 PPM 2 0 54. C=C. and the signal moves upfield relive to methyl ether. In the NMR. The signal for oxirane is shifted upfield because of the strain of the three-membered ring. only methylene. but it will also have a broad absorption at 2500-3000 cm–1. 2. O 4 2 PPM 0 3 2 O 1 0 PPM 56. The aldehyde unit has the polarized C=O bond. H O OH O OH 10 5 PPM 0 10 PPM 5 0 55. The carboxylic acid will have the carbonyl at about 1725 cm–1. the aldehyde will have the aldehyde proton peak at 2817 cm–1 and the carbonyl peak at 1725 cm–1.
5-Trimethylhexanal 2-Methyl-2.5. 61. 64. 3.3-butanediol OH HO OH 1.4-pentanediol 1. 60.3-Dimethylsuccinic acid .OH 2. 59.2-Epoxyhexane 2-Propylvaleric acid 2-Pentenal 2. 62.4-butanediol 4 2 PPM 0 4 2 PPM 0 58.
The ketal from this reaction would be a nine-membered ring. and has better coordination with the Mg of the Grignard reagent. In A. 58. but since the Grignard reagent is racemic. A N steric hindrance N B 62. React each with 2. 60. which helps to stabilize that product. H3O+ OH 59. The conjugated ketone will give an orange-red 2. which will react to give the product. Both are pentane-2-ones. 61. ether (S) MgBr 1. so the product will be a racemic mixture. and after formation of the Grignard reagent. which will hinder its formation.2-pentnaone 2. Note that the C=C-N unit is essentially planar in an enamine.4dintirophenylhydrazone whereas the non-conjugated ketone will give a yellowish 2. sp3 for carbon). the methyl group on the C=C unit will have steric interaction with the isopropyl groups on nitrogen. Vinyl Grignard reagents are less stable and they are more difficult to form because a C=C-X bond is stronger than a C-C-X bond (sp2 vs. the THF is a better Lewis base. Br Mg . Grignard regents are strong bases that will react with ethanol. O O hexan-2-one pentan-2-one pentan-3-one O O pentan-2-one 57. upon reaction with Mg. the Grignard reagent is configurationally unstable at the carbon bearing the Mg. which is an acid. Although 2S-bromohexane is a chiral molecule. In B. that particular methyl group can rotate away so there is less steric hindrance and this enamine will form faster than B. Reaction with 2-pentanone will give the alcohol. THF is a stronger Lewis base when compared to diethyl ether.4- . the alcohol is racemic and a mixture of diastereomers.4-dinitrophenylhydrazine. and it provides more coordination with the halide which assists in the Mg insertion. The transannular strain in ninemembered rings is so great that a cyclization reaction to generate such a ring will have such a high activation barrier that it simply does not form.Chapter 18 56.
O2N O O2N NO2 NHNH2 N H N NO2 orange-red O2N O O2N NO2 NHNH2 HN N yellow NO2 O KCN O– CN ClSiMe3 OSiMe3 CN 63. H N H Bu OH2 N Bu N-Bu H+ OH2 H –H+ N Bu H+ H H N Bu – H NBu 2 O H OH –H+ O OH 64. The two compounds are easily distinguished using this method. as shown. The enol form is stabilized by internal hydrogen bonding. 65.dinitrophenylhydrazone. . Such stabilization is not possible with simple mono-ketones.
leading to reduction of the ketone. coordination with the Mg-O leads to transfer of a hydride to the acyl carbon. Me2HC O (a) EtLi OH Et HO O (b) EtLi Me2CHMgCl HO Et OH CHMe2 OH Et CHMe2 Me2CHMgCl OH CMe3 (c) O H Me2CHMgCl CMe3 CMe3 EtLi . If acyl addition cannot occur. and reduction of the ketone BrMg O H O–MgBr+ H CH2=CH2 steric hidrance revents close approach of the Grignard reagent to the acyl carbon 67. loss of ethene. formation of ethene and transfer of hydride to the acyl carbon. A slower reaction involves coordination of the carbonyl oxygen with the magnesium.O O H O O 66. The carbonyl is too sterically hindered and the nucleophilic carbon of the Grignard reagent cannot come close enough for bonding.
69. which allows the carbonyl to undergo acyl addition in which a nucleophile donates electrons to the electron deficient carbonyl carbon. However. breaking the weak bond and forming an alkoxide product. In aqueous solutions 1. In addition. The C=O unit is polarized and the C=C unit is not. acyl addition reactions do not occur.(d) O Me2CHMgCl EtLi Me2HC OH Et OH O (e) Me2CHMgCl EtLi OH CHMe2 OH Et Me2CHMgCl (f) CHO EtLi Me2HC Me2CHMgCl (g) EtLi O Ph HO HO CHMe2 Ph OH Et OH Et Ph 68.1.1-trichloroethanal forms the hydrate (chloral hydrate). sulfuric acid is an oxidizing acid that may initiate unwanted sidereactions. Sulfuric acid is rather insoluble in organic solvents whereas p-toluenesulfonic acid is mostly soluble in organic solvents. If the carbonyl carbon is “tied up” as a hydrate. . 70. Both have a -bond and both will react as a Lewis base or a Brønsted-Lowry base. which is quite stable and there is a sizable concentration in aqueous media.
71. hemi-ketals O (a) H3CH2CH2CO OH ketals H3CH2CH2CO OCH2CH2CH3 O (b) OH OEt OEt OEt (c) O MeO OH MeO OMe OH O (d) O O O 72. (a) O NaCN O–Na+ CN (b) O NaOEt O–Na+ OEt (c) O NaC CEt O–Na+ C CEt O–MgBr+ Me (d) O MeMgBr .
H+ N H Me CHMe2 Me OH C3H7 Me N H • • OH C3H7 N H • • OH H OH • •N OH .H OH . Give the complete mechanism for each of the following transformations.H2O C3H7 N OH C3H7 H + Me .H OH H O H + H+ CH-H+ 3 C3H7 O C3H7 CH3 3H7 C O O C3H7 CH3 O + H+ C3H7 HO O CH3 H (b) C3H7 O + H+ Me H O H O Me N H C3H7 H + H+ C3H7 O Me Me C3H7 H .(e) MeLi O O–Li+ Me (f) O EtNH2 O– N H H 73. (a) O C3H7 + H+ CH3 HO O CH3 HO H O H .+H+ O CH3 H HOR HO + CH3 .H2O C3H7 C3H7 CH3 OH OH CH3 O H C3H7 O O OH C3H7 OH -H+.
and formation of the carbocation shown is destabilized (a C+ next to a C + would constitute a high energy intermediate).H+ C3H7 •• O H O C3H7 Et O O O •• H OH H +H+ -H+ OH + H+ C3H7 Et O H 74.EtOH H + EtOH C3H7 Et O H Et H -HOEt C3H7 Et O H H C3H7 H C3H7 O O H C3H7 H H . loss of water cannot easily form an enol.H+ H N •• Et (d) C3H7 Et -H+ O + H+ HH+ O H H +H2O C3H7 Et O H . and loss of water to the enol and tautomerization back to the aldehyde is facile.H2O H N . Formation of the hydrate from B is straightforward.H (c) O + H+ H O H O N OH N . so this hydrate is not very stable. Phenylglyoxal (A) forms a relatively stable hydrate because of the stabilization provided by the adjacent electron withdrawing carbonyl group.H+ BASE H OH + H+ N •• O N •• Et H . In addition. O O O A CHO OH OH CHO B OH OH OH OH .
The transannular strain inherent to a 9-membered ring poses an energy barrier that is too high for formation of this ketal. TsOH H2O/THF cat. From a synthetic viewpoint. Note also how the R/S configuration changes when the ring system is opened to the cyclic ketone since there are now two OH units.75. Note that any synthesis must account for the absolute stereochemistry of the groups in the acyclic ketone in order to generate the ketal with the correct stereochemistry. and then again in the extended conformation. TsOH H2O/THF O + HOCH2CH2OH O + 2 MeOH O + 2 EtOH . OCH2CH3 (a) OCH2CH3 (b) H3CO O (c) O OCH3 cat. the ketal is formed from the ketone shown. The molecule is drawn in the same perspective as B to show the stereochemical relationships. Formation of the ketal from 1.8-octanediol requires formation of a high energy 9-membered ring. H (R) HO (R) H O (S) B (S) H O (S) O (R) HO H (R) PhH2CO H OCH2Ph PhH2CO H OCH2Ph OCH2Ph O PhH2CO (R) (S) (R) OH OH 76. whereas formation of the ketal from 1. TsOH H2O/THF cat. O O O O 77.3-propanediol requires formation of a stable 6-membered ring.
OCH2CH2CH3 (d) OCH2CH2CH3 S (e) S O (f) O SCH3 (g) SCH3 Ph Ph cat. TsOH H2O/THF SH CHO + 2 CH3CH2CH2OH PhCHO SH O Ph OH OH O + 2 CH3SH 78. TsOH H2O/THF BF3 . H2O THF Ph Ph BF3 .H+ C5H11 O O Me H C5H11 Me C5H11 Me •• O •• OH H H . H+ O (a) H+ OH2 OEt OEt Ph (b) H Et (c) C5H11 Et -H+ + H+C5H11 Et Et H O EtOH OH O Et H –H+ OH OEt –H+ H O Et –H+ OEt OEt –H+ H H Ph OH OH H H H+ Ph O H + H+ MeH+ O H H O H2O Ph OH H O H O .EtOH Me + EtOH OH -HOEt C5H11 Et O C5H11 Me Et O Me +H2O C5H11 Et O O C5H11 Et O O Me +H+ Me -H+ C5H11 Et O O Me . H2O THF cat.
H2O S SH SH S H S S .H2O Bu C3H7 O H OH OH O H O O Bu H Bu HO O H (e) O + H+ H O H HS O SH S HS OH -H+.1-dimethoxycyclohexane S .4-diphenyl-1.+H+ OH + +H S -H+ H HSR HS H O H .+H+ O H H HOR HO H O O Bu H .1-diethylthiopentane 2.H+ + H+ S S HS S 79.3-dioxane 4-phenyl-1. O O O O S 1.H+ + H+ Bu OH + H+ H -H+ O Bu Bu HO H O H .(d) O Bu H + H+ H O H H HO O H OH Bu OH -H+.2-dimethyl-4.
The mixed OH-SH thiohydrate should be very unstable. In each case.4-dimethylhexane H+ S S O H+ –H2S H EtOH OEt O OEt Et Et –H+ OEt OEt H EtOH SH H –H+ SH OEt SH2 OEt 80. Yes. .O O O O 2-butyl-1. and it should be possible to treat A with BF3 under conditions that will convert the dithiolane to a ketone. just like a hydrate. H+ O H3C H3C O H H2S OH H3C S H SH2 H –H+ H3C OH SH OH2 H3C SH H3C SH H3C SH H3C SH SH 82.3-dioxolane 2. Dilute acid hydrolysis will convert the dioxolane to a ketone. Given this instability. undergo elimination and revert back to the ketone. it is very unlikely that any of the thiohydrate product (HS-C-SH) will ever be formed under these conditions. 81.2-(diisopropoxy)-3. the other protected carbonyl will not be hydrolyzed.
and the oxonium salt formed from ether does not have a proton that can be re moved. H+ Ph (f) O O NH PhNHNH2 . H+ (b) O O (c) pyrrolidine . H+ N-NHPh HO OH O O Ph BuO OBu Ph OH Ph cat. The major product or products are shown. cat. H+ (d) O CHO (e) cat. so the reaction is reversible and cannot proceed to product.H+ N O . H+ Ph Ph (g) O cat. cat. Ether is a weaker nucleophile when compared to ethanol. H2O-THF S O O S A 83. 84. H+ NH2 N N cat. (a) CHO NH2OH CH=NOH cat. No mechanisms are provided.O O TsOH H2O/THF S S O O BF3.
86.O-ketal shown. PhMgBr 3. COOH COOH H + CN O CN H O O O HO HO HO HO HO HO Ph Ph A CN CN CN -H+ H2O HO COOH H2O Ph Ph Ph O OH HO HO HO H H -H+ O – –CN O H Ph Ph OH (a) (b ) CN CN OH (c) CN OCH3 87. . H+ O (i) 1. Compound A is an acetal. The logical product is the enamine.4-dinitrophenylhydrazine cat. formed by the usual mechanism. cyanide is released as a leaving group. For all practical purposes it is just an ether. 88. laetrile kills cells by exposing them to deadly cyanide. but it is unlikely there is any selectivity for cancerous cells versus normal cells. H3O+ 2. Presumably. MeCO3H 2. The yellow color indicates that there is a non-conjugated ketone. Acid hydrolysis will lead to the sugar shown. Along the way. and benzaldehyde. and subject to the hydrolysis mechanism discussed in this chapter. H+ Ph N H N + HOCH2CH2OH NO2 NO2 (j) OH 85. Compound B is not as susceptible to hydrolysis.O (h) O O H2O cat. 89. and acid hydrolysis of an ether is very difficult unless HI or HBr is used. An alternative product arises by interaction of the pendant hydroxyl group with the iminium salt (or another intermediate) to form the cyclic N.4-dintirophenylhydrazone derivatives. Conjugated ketones give orange to red-orange 2.
H H H H+ O O O O O O O O H2 CH2 C O O O O OH2 A H H O O O H2 O O H2 C formaldehyde C HO OH H H O OH H .O O H A H N OH OH N OH OH OH N N OH2 OH N OH N OH N O 90. All three C-O units of trioxolanes are converted to three equivalents of formaldehyde upon acid hydrolysis. Hydrolysis of trioxolane eventually leads to the hydrate of formaldehyde. which is converted to formaldehyde.
Mg/ether 2. ether 2. Mg/ether 2. 1.91. removing one product from the reaction shifts the equilibrium towards product. CH2Cl2 2. (b) phenylmagnesium bromide + 1. cat BF3 SBu SBu (b) 1.7. 2-butanone 3. dilute aqueous acid. Li 2. dicyclopentylmethanol. H3O+ O CrO3 . cyclohexanone 2. 93. (e) butylmagnesium chloride + water. CH3CH2MgBr . dilute aqueous acid. In an equilibrium. (c) iodomethane + 1. cyclopentanecarboxaldehyde 3. ether OH (c) OH OH 3. dilute aqueous acid. (g) 1-iodopentane + 1. (k) methyllithum + 1. 4-ethyl-2-phenyl-2-heptanol. dilute aqueous acid. This is a multi-step reaction in which each step is reversible. CH3C C–Na+ . 3-methyl-3-octanol. (a) 2-iodopentane + 1. 92. 3-pentanone OH (a) Br O 3. 1-phenyl-1-hexanol. dilute aqueous acid. 1-propyne 2. H3O+ OH C CCH3 . acetone (3) dilute aqueous acid. the equilibrium shifts to produce more of both products. dilute aqueous acid. aq acetone H2SO4 (d) Br 1. (i) n-butyllithium + 1. 3-phenylpropanal 2. 6. (h) phenyllithium + 1. butane. 1-propyne. (d) bromocyclopentane + 1. PCC . the equilibrium shifts and helps to drive the reaction towards the acetal or ketal. 4-phenyl-2-butanol. The product or products are shown. phenylcyclohexanol. H3O+ 2 BuSH . THF 2. If two products are formed and one is removed. which is a product along with the acetal or ketal. acetone 1. Mg . 1-butyne.7-trimethyl-6-undecanol. dilute aqueous acid. (j) n-butyllithium + 2-phenyloxirane followed by an aqueous acid workup. 2-pentyne. By removing water. Mg/THF 2. H2O . (f) 2-methylhexylmagnesium bromide + 1. Mg . No mechanisms are provided. 2-hexanone 2. ether (e) CHO (f) 2. 4-ethyl-1-phenyl-1-heptanone 2. 2-methyl-2-heptanol.
aq H+ 1. PCC 4. PCC 2. (a) 1. OsO4 . heat HO O HO N 2-butanone . t-BuOH 2. PCC 4. H3O+ HO OH Ph OH (c) (d) 94. cat H+ (h) CH3CH2NH2 MgI 1. NaNH2 . H3O+ OH (b) Br 1. MeNH2 . MeMgBr 3. H+ N CH3 . HIO4 3. Do not attempt these problems until you have read and understood chapter 25. 2-hexanone 3. excess PhNHNH2 .O (g) O aq H+ . H3O+ 1. NaBH4 3. HO 2. THF 2. H+ OH CH=NNHPh CH=NNHPh (j) Synthesis. PhMgBr . THF 2. Mg . O (a) 1. cyclopentanone I 3. Me2CHCH2MgBr OH (b) OH 1. NH3 2. 95. (i) O 2. Hg(OAc)2 .
1 ppm suggests a ring. NaBH4 3. Me2NH . Two groups will be on nitrogen in an enamine.5 ppm. H2O 2. In the proton NMR. BF3 . H+ 7.8-2. HIO4 1. Depending of the nature of the groups on nitrogen. Spectroscopy Problems. There are characteristics of fragmentation for four-membered rings. There is a distinct ethyl group in the NMR.5-5. Me2CHMgBr 3. cat H+ NMe2 96. PCC 4. ethylene glycol cat H+ 1. 98. H2O-THF 2.SEt (c) SEt 1. PCC 2. MeMgBr 8. but there is no way to absolutely correlate this with a four-membered ring. there may be other differences in the NMR. PBr2 NNHPh NNHPh 4. EtOH 5. . Hg(OAc)2 . and only one on the nitrogen in an imine. PCC 3. Me2CHCH2MgBr 2. Differences between an imine and the alkene unit of an enamine are minimal. The collection of methylene groups at about 1. MeCO3H 6. PhMgBr OH O O (e) CHO (f) CHO 1. whereas an imine will not. KOH . excess PhNHNH2 . BuMgBr 2. but they have not been discussed in this book. EtOH (d) OH 1. MeMgBr 3. and a prominent M-18 peak. The mass spectrum will show a weak molecular in. KOH. so the only reasonable thing to be gained from the mass spectrum is the presence of ethyl groups and the suggestion of an alcohol. 97. PCC 3. There will be a prominent M-29 peak for loss of an ethyl group. Do not attempt these problems until you have read and understood chapter 14. PBr3 4. and integration will reveal that there are two ethyl groups. an enamine will have an alkene H between 4. in accord with a tertiary alcohol.
but there are many more possible isomers. which is consistent with the number of -bonds. If a yellow precipitate forms. it is the ketone. then it is the ketal. There are two rings or -bonds. 100. If that peak is missing. If the yellow precipitate does not form. as does the 2. it is the ketone. one further downfield than the other as it is next to the carbonyl. There is nothing to indicate the specific structure of the sevencarbon conjugated ketone.4-DNP derivative. The absence of a peak at 2270 cm–1 indicates that it is not an alkyne. If the IR shows a peak around 1725 cm–1. The absence of a peak at about 2800 cm–1 indicates the compound is not an aldehyde. and one of them is a carbonyl. The position of the carbonyl suggests a conjugated carbonyl.4-DNP test. very slowly. C8H 14 O. including two different alkenyl protons and two different methylene groups. so it is indeed an acyclic conjugated ketone. it is likely the desired product. One can do a 2. The conjugated ketone (2-cyclopentenone) will show a carbonyl at about 1695 cm–1 whereas the non-conjugated ketone (3-cyclopentenone) will show a normal carbonyl at about 1725 cm–1. The NMR of 3-cyclopentenone is rather simple. O O 101. 102. or forms very. Two examples are shown. . showing only one type of alkene proton and the methylene protons adjacent to the carbonyl. so it is a conjugated ketone. 2-Cyclopentenone shows several peaks.OH 4 3 2 PPM 1 0 O 99.
O O 6 4 PPM 2 0 6 4 PPM 2 0 103. NaOH H2O2 MgBr Mg E OH B O PBr3 C Br 109. 9-BBN A 2. 106. 107. D . 104. 105. 108. 1-Phenyl-2-butanone 4-Phenylbut-2-en-2-one 1-Phenyl-1-butanol Benzaldehyde diethyl acetal -Hydroxyphenylacetonitrile 1-Hexyn-3-ol OH 1.
The OMe groups attached to Al in LiAlH(OMe)3 are electron withdrawing. 35. so it is a stronger reducing agent than NaBH4. . which emphasizes the – polarization of the H (a hydride).chapter 19 CO2Me (a) OH reduction Br (c) reduction CHO (e) CO2H (f) oxidation (d) oxidation O OH CH2OH (b) reduction O C N CH2NH2 29. so the Al-H bond is more reactive. 31. Lithium aluminum hydride will react with water in an acid-base reaction. CH3CH2CH2CO2–Na+. The electron releasing NaBHEt3 makes the B-H bond more polarized (more –). Note that it is often difficult to do this with NaBH4. O O O O O O O O 33. The product is the sodium salt of butanoic acid. Reduction of 5-oxooctanal with NaBH4 reduces the aldehyde first because it is less hindered and more reactive. but if the stoichiometry and reaction time are carefully controlled. 32. which makes The Al-H bond less polarized (less –). but it has sometimes been more broadly defined as a mixture of different elements. so it is weaker than LiAlH4. 30. Sodium borohydride is not a strong enough reducing agent to reduce the carboxylic acid. it is possible to selectively reduce the aldehyde in the presence of the ketone. 34. The Al-H bond in lithium aluminum hydride is more polarized than the B-H bond in sodium borohydride. Excess reagent will reduce both the aldehyde and the ketone units. An amalgam is most commonly an alloy of mercury with another metals.
ether (g) CO2Et 2. aq. NH3 (h) EtOH . KOH 1. Pd-C 1. MeC C:–Na+ . No mechanisms are provided. NH4Cl OH 1. H2 . which makes The Al-H bond less polarized (less –). The electron releasing NaBHEt3 makes the B-H bond more polarized (more –). LiAlH4 . EtOH (e) OH CH2NH2 (f) O 1.CHO NaBH4 O O CH2OH 36. THF N-NH2 2. NaBH4 . aq. refluxing acetone (b) Br 2. H+ CH2OH + EtOH Na . PCC . Ni(R) . NH4Cl 1. NH2NH2 . O OH (a) 1. EtOH 3. so it is weaker than LiAlH4. ether 2. THF 3. aq. KOH . the OMe groups attached to Al in LiAlH(OMe)3 are electron withdrawing. Lithium triethylborohydride is LiBHEt3 and lithium trimethoxyaluminum hydride is LiAlH(OMe)3. CH2Cl2 (c) OH (d) Br 2. EtOH 2. Pd-BaSO4 quinoline 1. NaCN . As noted in question 30. so it is stronger than NaBH4. KI .LiAlH4 . 2 H2 . 37. PBr3 2. H2 . The major product or products are shown.
OMe OMe OMe OMe OMe 42. the more coordination. PtO2 (k) O MeOH excess H2 OH (l) CH3 Ni(R) . NH3 O OH H2 . . EtOH CH3 38. heat . While cyclopentene readily coordinates to palladium and is easily hydrogenated 1. Hydrogenation is a surface reaction in that the hydrogen must coordinate with the surface of the metal in order to break the H-H bond to form hydrogen radicals coordinated to the metal. with the OMe group of a C=C unit. so the hydrogenation is much slower.2-ditert-butylcyclopentene has a sterically hindered C=C unit that inhibits approach to and coordination with the palladium. The most stable radical anion will NOT have the negative charge on the carbon bearing the OMe group in any of the resonance contributors. Cycloheptanol. and the product is the diene shown. Triphenylmethane (Ph3C-H). The larger the surface of the metal. 39. 43. and the faster will be the rate of the reaction. LiAlH4 H H O H3Al O O H3Al 40. 41. Hydrogenation requires that the C=C unit of the alkene coordinate to the surface of the transition metal catalyst. Likewise. Pd-C EtOH O (j) Cl O H H2 . The resonance contributors formed are those formed in this reaction.(i) Na . The electron is transferred to the benzene ring at a carbon that generates a radical anion. the C=C unit must coordinate to the surface of the metal.
treatment of hex-5-enal with one equivalent of H2 and Pd-C catalyst. aq. 46. ether + CHO 2. aq. Therefore. NH3 EtOH CH2OH Et Na° . NH3 EtOH OMe O H OH H2 .44. H3O (a) O (b) OH OH 1. NH4Cl CHO (c) Et (d) O (e) Et Na° . EtOH 2. if hex-5-enal is reduced with NaBH4. Hydride reducing agents do not reduce non-conjugated alkenes. the product will be hex-5-en-1-ol. usually in ethanol or methanol. Therefore. Hydrogenation using a palladium catalyst has a greater affinity for reduction of alkenes relative to carbonyl compounds. The major product or products are shown. PtO2 MeOH Et OMe OH H2 . PtO2 (f) O MeOH OH .NaBH4 . O A 1. LiAlH4 . NaBH4 CO2Et 2. although some reduction of the aldehyde will undoubtedly occur to give 1-hexanol. NH4Cl OH CO2Et B 45. 1. Reduction of hex-5-enal to 1-hexanol is easily accomplished using a large excess of hydrogen gas with a palladium or platinum catalyst. No mechanisms are provided. should give hexanal as the major product.
H3O+ 1. NH4Cl O OH 47. NH3. LiAlH4 2. H3O+ OH 1. (f) 4-phenyl-1-pentane + 1. NH4Cl excess H2 PtO2 . LiAlH4 . PtO2 MeOH O OH O (h) OH excess H2 PtO2 . Hot water. Hydrolysis 3. ether 2. aq. PCC. EtOH. No Reaction. Z-3-heptene.NaBH4 . (a) 2-hexyne + Na. (b) 2-pentanol + LiAlH4 . lithium salt of 2-pentanol (lithium 2-pentoxide). Mg. Give the product of each individual step where appropriate. (c) 3-heptyne + H2. EtOH 2.NaBH4 . aq. MeOH CH2OH OH OH 1. mOH OH OH CHO (i) O O (j) O (k) H CO2Et (l) O (m) 1. and the final product for each of the following. H3O+ CH2OH OH O (n) OH 1. LiAlH4 . (e) ethyl butanoate + 1. Pd/BaCO3/quinoline. ether 2. LiAlH4 .(g) H2 . . ether 2. E-2-hexene. ether 2. EtOH 2. 1-butanol and then butanal.
(g) cyclopentanone + 1. EtMgBr , ether 2. H3O+ 3. Br3 4. Mg, ether 5. Hot water Ethylcyclopentanol and then 1-bromo-1-ethylcyclopentane and then the Grignard reagent and then ethylcyclopentane. 48. In this reaction the ammonia functions as an acid in the presence of the carbanion intermediate (R3C– + H-NH2 R3C-H + –NH2). Ethanol is a much stronger acid when compared to ammonia, so ethanol is added to accelerate the protonation of the carbocation intermediate. 49. Transfer of an electron generates a ketyl, and it is possible for two of the ketyls to undergo a coupling reaction via a radical coupling reaction to give the dimer shown. Hydrolysis leads to a vicinal diol.
O O O O O OH H3O+ OH
50. Give the major product for each of the following reactions. (a) methyl 4-phenylbutanoate + 1. LiAlH4 2. hydrolysis . methanol + 4-phenyl-1-butanol. (b) 3-methyl-2-hexanol + 1. PCC 2. NaBH4 3. aq. NH4Cl. 3-methyl-2-hexanol. (c) 2R-bromopentane + 1. NaCN, THF 2. SnCl2/HCl. 2-methylpentanal. (d) cyclopentanecarboxaldehyde + 1. NaBH4/EtOH 2. hydrolysis. cyclopentylmethanol. (e) 2-bromo-2-methylpentane + 1. KOH, EtOH 2. EtOH. H2, Pd/C. 2-methylpentane. (f) 3-phenylpentanal + 1. NaBH4 2. hydrolysis 3. PCl5 4. KOH . EtOH, H2, Pd/C. 3-phenylpentane. Synthesis. Do not attempt these problems until chapter 25 is read and understood. 51. 1. Ozonolysis followed by treatment with dimethyl sulfide. 2. Dihydroxylation followed by treatment with periodic acid. 3. Formation of an alcohol using oxymercuration or hydroboration, followed by oxidation with PCC or PDC. 4. Epoxidation with peroxyacetic acid followed by reduction with LiAlH4 and then oxidation with PCC or PDC. 52. Provide a synthesis for each of the following.
1. Br2 , CCl4 2. excess KOH , EtOH 3. NaNH2 4. EtI 5. Na, NH3 , EtOH
1. HBr 2. Mg , ether 3. CH3CH2CHO 4. H3O+ 1. HBr 2. Li 3. CuI , ether 4. EtI OH 1. SOCl2 , NEt3 2. NaCN , DMF 3. LiAlH4 4. H3O+ 1. Sn , HCl Cl 2. NaBH ; 3. aq. NH Cl 4 4
4. PBr3 1. LiAlH4 2. H2O 3. PBr3 4. HC C:–Na+ 5. NaNH2 6. MeI 7. H2 , Pd-BaSO4, quinoline
1. BH3 , ether 2. NaOH , H2O2 3. PBr3 4. Ph2CuLi 1. LiAlH4 2. H2O 3. PCC 4. EtMgBr 5. H3O+ 6. NaH and then MeI OCH3
Spectroscopic problems. Do not attempt these problems until chapter 14 is read and understood.
Little difference in IR HO 3-phenyl-2-pentenol ethyl group HO 3-phenyl-4-pentenol
one alkene H
3 alkene H
IR: the alcohol has a broad peak at 3300 cm–1 and the aldehyde will have a peak at OH 1725 cm–1 and the aldehyde H at 2817 cm–1 4-methylpentan-1-ol 4-methylpentanal
aldehyde H is absent in the alcohol
O OCH2CH3 IR: Ester has a carbonyl at about 1725 cm-1 and the alcohol has a broad peak at about 3300 cm-1
The ester has an ethyl group, with the CH2 group connected to O. The alcohol has a CH2 gourp attached to O, but it is not part of an ethyl group. The braod OH protn will also show up in the alcohol - here at about 3.8 ppm
56. The aldehyde proton is pushed downfield by a combination of electron withdrawing inductive effects of the C-O bond plus the anisotropy of the carbonyl -bond. The alkene has only the downfield shift due to anisotropy of the -bond, but there are no inductive effects.
OH no difference in the IR OH
a doublet methyl
A CN D
B CHO E
Chapter 20 86.
O O (a) OH 16-phenylhexadecanoic acid 2,2-diethylcyclobutane-1carboxylic acid O (c) OH O OH 1-butyl-1,4-butanedioic acid Br OH 3,3-diethyloctanenitrile O (d) OH (e) CN (b) OH
O CO2Me Br Br O Br (c) O 3,3,5-trimethylheptanoyl bromide
3-methylbutan-2-yl cyclopentanecarboxylate methyl 3,5-dibromohexanoate Ph (d) O (e) Cl O N
O O Ph 3-methyl-2-phenylbutanoic 3phenylpropanoic anhydride
CONMe2 CHMe2 3-chloro-N-ethyl(1R,2R)-N,N,2N-isopropylpentanamide trimethylcyclohexanecarboxamide
(h) CO2Et ethyl 3-isobutyl-2,2,5-trimethylhexanoate
O O cyclopentanecarboxylic 1,1-dimethylethanoic anhydride
Ph 94.5-dimethylhexanenitrile NH2 N O H O O N O O 88. PBr3 SOCl2 CH3Cl PCl5 NaCl 89. 90. chloride ion would have to react via an acyl substitution reaction in which chloride ion displaces hydroxide. The by-product of the reaction is the strong acid trifluoroacetic acid. Mg 2. Ph 93. In addition. 250°C Br 1. OH Ph .2-dimethylhex-3-enenitrile 2-ethyl-2. 25°C Me2NH . 91. NH3 .(i) (E) CN (j) CN (E)-2. 92. Reaction of the acid with HCl forms an oxocarbenium ion. NH3 . with is more stable than the oxonium in derived from an alcohol. heat Ph O Cl O Me2NH . MeOH . given that hydroxide is a very poor leaving group. 25°C 1. An alcohol reacts with HCl to form an oxonium ion. and chloride ion can displace water to form the chloride in a substitution reaction. and chloride is not a strong enough nucleophile to do that. SOCl2 2. OH Ph H Ph Ph Ph OH2 OH2 Ph Ph 95. H+ 2. NH3 1. The buffer is added to prevent this acid from reacting with the product and causing unwanted secondary reactions.
NaCN . heat Cl (b) CO2Et cat H+ . H2O heat O HO OH CN (e) 1. CH3COOH O O CO2Et (g) 1. No mechanisms are provided. NaOH 2. H+ CH3CH2NH2 20°C O–+NH3Et Cl Cl . O O SOCl2 (a) OH Me2NH . DMF O (f) CO2H 1. SOCl2 2. dilute H3O+ CO2H + EtOH O NEt2 O O (h) NEt2 O (i) OH EtOH .96. reflux cat. butanoic acid heat . aq. HBr 2. The major product or products are shown. drying agent O O NMe2 (c) OH C3H7 O O (d) O cat H+ .
Since reaction with hydroxide or with water under acid conditions requires a nucleophilic attack the acyl carbon. Acid chlorides do not have these hydrogen bonding OH groups. 104. regardless of conditions for how the intermediate was formed. and efficiently forms hydrogen bonds. which leads to an aerosol of hydrochloric acid. Because the acid catalyzed reaction is reversible. and any unreacted acid chloride is treated with water and the resulting carboxylic acid is washed with sodium bicarbonate to remove it. DMF CN 97. The fuming occurs when gaseous HCl is produced in the presence of moist air. and only a five-fold excess of isopropanol is probably insufficient to compensate for the difference in rate. Making the acid chloride is usually a high yield procedure and the subsequent reaction with an alcohol is rapid and proceeds in high yield. whereas an amide is less reactive and much more difficult to hydrolyze. 99. loss of OR will always produce the amide. The bicarbonate is a base. 100. with no methanol. Using this procedure there are usually no other products. Ethoxide is a far better leaving group when compared to a dialkylamide. which are weaker . The solution is to use isopropanol as the solvent. SOCl2 4. H2O2 3. removal of the water product is necessary by the use of a dehydrating agent or removal via azeotropic distillation. and some esters are sensitive to heat. BH3 . Once this intermediate is formed. Acetic acid has OH groups with acidic protons. In both reactions the tetrahedral intermediate shown is the intermediate. the reaction may be incomplete and with higher molecular weight esters both of these procedures are problematic. 101. The product was methyl butanoate.(j) 1. Either way. if that carbonyl is sterically hindered the reaction will be much slower. NaCN . In one sense this is a silly question.1-dimethylethyl butanoate relative to methyl butanoate. –O OR R2N R 103. from reaction with methanol. 102. The acetyl chloride is so reactive that it reacts with the water in the air to for acetic acid and HCl. 98. and it reacts with any unreacted hexanoic acid. Methanol is more reactive than isopropanol. which is water soluble and easily washed away from the ester product. Drying agents are often inefficient. The adjacent methyl groups sterically inhibits approach to the carbonyl carbon in 1. The extensive hydrogen bonding in the acid must be disrupted before individual molecular of the acid go into the gas phase (boiling point). ether 2. but the point is to say that an ester is more reactive and easily hydrolyzed. NaOH . This reaction generates the carboxylate anion of ethanoic acid. This means that the amide is more robust and many chemical processes may occur without disrupting the amide bond. so the only forces available for association of molecules are dipole-dipole interactions.
NaOH then neutralize with H3O+ 2. An acid chloride is very reactive. so washing an acid chloride with aqueous bicarbonate or acid will hydrolyze the acid chloride to the corresponding acid. Me2CHOH . 200°C NMe(Bu) O CO2Bu CO2H 1. P2O5 1. The major product or products are shown. NEt3 O (b) CO2Me 1. so acid chlorides will have a lower boiling point. Removing one product in this way drives the reaction towards the desired ester product. 108. No mechanisms are provided. cat. 105. Me(Bu)NH 3. phosphorus pentachloride. ammonia 2. (a) CO2H 1. This means that disrupting dipoledipole interactions requires less heat. Washing with aqueous bicarbonate will convert all of the unreacted carboxylic acid to the salt. MeOH . The second product in this reaction is HCl.and more easily disrupted when compared to hydrogen bonding. Triethylamine is added as a base. 107. The water soluble ammonium salt is easily removed form the ester by simply washing with water. aq. Ac2O 2. 106. which is removed by washing with water. H+ CN O (f) CO2H O . NEt3 2. SOCl2 2. phosphorus oxychloride. H+ NEt2 3. cyclopentanol . SOCl2 2. oxalyl chloride. PCl 5 (c) O (d) O (e) OH Cl 1. leaving behind the neutral amide. EtOH . cat. butanoic acid O 1. Thionyl chloride. Reaction of triethylamine with HCl gives triethylammonium chloride (HEt3N+Cl–). phosphorus trichloride. which defeats the purpose of making the cid chloride in the first place. phosgene.
Inside the body. Such reaction products produce many problems in humans once inhaled. which is unstable and decomposes to carbon dioxide and water. When thionyl chloride is exposed to water. especially if inhaled. Note also phosgene may be inhaled without hydrolysis. 111. reflux (h) (i) (Z) CO2Me EtOH (solvent) cat. cat. 6N HCl 2. The whitish gas is HCl and exposure to moist air will produce an aerosol of hydrochloric acid. EtOH . It is likely that the gaseous HCl. phosgene can react with the amine units of proteins. producing HCl gas and eventually carbonic acid (HOCO2H). which when exposed to moist air forms an aerosol of concentrated hydrochloric acid. H+ CO2Et CO2Et CO2Et 109. + + N C N H H O O H N C N O O O O H N C N O O H N C N O O O + N H C N O O H O H O O . is responsible for the damage. When phosgene is exposed to water (moist air) it reacts as a highly reactive acid chloride. forming crosslinked urea structures. which is highly corrosive.OH O O (g) CO2H DCC diethylamine . reflux (Z) CONEt2 CO2H (j) CN CO2H 1. the hydrolysis produces are sulfur dioxide (SO2) and HCl. 110. H+ .
H+ AcO (a) O O O 1-aminobutane (d) O (b) reflux O O H3O+ CO2Me MeNH2 heat 115. cat. due to diminished transannular interactions and less torsional strain in the five-membered ring. Give the major product for each of the following reactions. . then formation of the fivemembered ring lactone is faster than formation of the seven-membered ring lactone. It is difficult to form a 17-membered ring because it is difficult for the distal OH group to attack the acyl carbon. 114. O (c) EtOH . the transition state assumes the conformation of the ring being formed. H+ O O 113. the intermolecular ester forming reaction is more favorable than the intramolecular lactone-forming reaction. O A heat HO H+ O HO H – H+ OMe O – H+ OH O H OMe O O H+ OH Me O O H O – MeOH OH Me H OMe cat. In other words. so the more common product is the ester shown. If formation of the five-membered ring is lower in energy in the transition state.112. A five-membered ring is lower in energy than a seven membered ring. As the lactone ring is formed by cyclization.
O O HO OH O HO O O O OH 116. which effectively shortens the C-N bond length O O R NH2 R NH2 117. The amide has resonance contributors that delocalize the electron pair on the oxygen. 4-Aminobutanoic acid has a basic amine unit and an acidic COOH unit. OH O H2N H3N O O 118. O (a) NH OH O O (b ) NH Cl O O (c) NH OEt N O H2N O N . An internal acid-base reaction occurs to form the zwitterion shown.
H–Cl O O O
no reaction (N.R.)
O Cl O H2N NH2 O Cl O H N NH n
A O Cl
CO2H NH O 2 Cl O
SOCl2 EtOH EtO2C
EtO Cl O
O OH 1. propylamine 2. 250°C O N H
O Cl O OMe
O N H
O N H
122. The leaving group for acetic anhydride is acetic acid whereas the leaving group from the imide is the amide, acetamide. In acyl substitution reaction, the amide is a poor leaving group, and reactions with the amide simply do not give the acetylation reactions observed with the anhydride. H Me O Me N Me Me versus
O (a) (b)
O O Ph Ph (c) OH (f) Ph Ph Ph OH Me Me O O (e)
125. The Cl is a good leaving group and acyl substitution with an acid chloride is much faster than acyl addition to the ketone. In other words, the cid chloride is much more reactive.
O (b) (c)
(g) HO (j)
(i) OH (k) CN
O C3H7 OH OH C3H7 OMe
H + H+ C3H7 OH + H+ C3H7 H OMe H - H2O C3H7 O OH C3H7 O
OH + MeOH C3H7 OH O H - H+ C3H7 O OMe Me - H+
OH O H + MeOH OMe C3H7
O RCO3H O 1. BH3 , ether 2. NaOH , H2O2 3. PCC 4. Me3CMgBr 5. H3O+ 6. PCC 7. MeCO3H
129. The major product or products re shown. No mechanisms are provided..
OH (a) + N H CrO3Cl MeO (b) O OH
1. MeMgBr , ether 2. aq H+ 3. cyclopentanecarboxlic acid H+ catalyst
excess H2O in THF cat H+ 1. SOCl2 2. Mg , ether 3. 0.5 ethyl butanoate 4. H3O+
1. SOCl2 2. 2-propanol
CO2CHMe2 O Ph
1. CrO3 , H2SO4 , aq acetone 2. SOCl2 3. Ph2CuLi , THF , 0°C
1. SOCl2 2. MeNH2
1. SOCl2 2. Me2CHCH2OH 1. KCN , DMF 2. H3O+ , heat 3. Me2NH , DCC Me3CO3H
SO2OCH2CHMe2 O NMe2
O O O
O + H+ NMe2 OH R Me N Me H H R OH O NMe2 R OH NMe2 + H2O R H O NMe2 H H - H+ - H+ R OH OH NMe2 + H+
OH OH R
131. Conversion of 1,8-octanedioic acid to the corresponding anhydride requires formation of a 9membered ring, whereas succinic acid generates a 5-membered ring anhydride. The transannular interactions of the 9-membered ring raise the activation barrier for cyclization to that ring so high that it does not easily form. Formation of the lower energy 5-membered ring is energetically easy. O O
CO2H O CO2H O CO2H CO2H O O
1. O3 2. H2O2
O O O H+ 2-phenylethylamine cat H+ O H O N O +RNH2 H O N O O H H -H+ Ph O H H+ H O N O O H HO Ph HO Ph -H2O N Ph OH H+ -H+ O N Ph H OH H2O H N Ph OH O O OH O O O O O N Ph -H+ N Ph
O H+ O O HO H+ OH O O H
O O O
H + H2O
OH -H+ O O
OH O O
O OH OH O -H+
O OH OH O
O (a) H3C S O OEt (b) H3C S
O NEt2 (c) H3C S O O O (d) H3C S
H OH Synthesis Problems. EtO O P O EtOH EtO EtO O P OEt HNMe2 EtO EtO O P NMe2 139. EtO Cl NH2 N O -O N N P O- O H H OH O H N 140. Do not attempt these problems until you have read and understood chapter 25.136. O O O MeNH2 . SO3H NaOH SO3–Na+ 137. . O HO P OH O O O P OH O O O P OH O O O P O O O S O O 138. heat O N-Me O 141.
EtOH CO2Et (e) (f) 1. Mg . SOCl2 O Cl . PCC 5. ether 2. EtMgBr 6. PCC OH 1. aq NH4Cl 7. ether 2. NaOH 3. KOH . Show a complete synthesis for each of the following from the indicated starting material. O3 . PCC 4. EtMgBr 8. Mg . EtOH CN 1. propanal (a) 4. Me2S 6. heat (c) 2. NaBH4 . NaBH4. 143. H3O+ O O 1. 1. 9-BBN . H3O+ 7. PBr3 8. NaOH . SOCl2 NH2 OEt 3. KOH . SOCl2 3. ether 9. EtOH CHO 1. EtOH 5C 4. H2O 10. HBr O 2. BH3 .(a) (b) SO2OH SO2Cl SO2Cl SO2OH SOCl2 EtOH SO2Cl SO2OEt SO2NH2 SO2O–Na+ (c) (d) NH3 NaOH 142. –78°C 5. heat 2. NH4Cl 2. H3O+ . ether 3. PBr3 11. H3O+ . H2O2 . benzophenone . PBr3 6C Ph (d) Ph 3. H2O2 (b) 3. aq.
Extensive hydrogen bonding of the carboxylic OH effectively makes it more positive (large +). and an anhydride (if this is possible). HOCH2CH2OH cat H+ O O Spectroscopy Problems. 146. 144. O O R NH2 R NH2 147. Describe how to use the signals in the 1500-2000 cm-1 region of the IR spectrum to distinguish between a carboxylic acid. with triplet at 4. the less electron density. H3O+ . Since both forms of the amide are usually present. an acid chloride. heat 3. Me2CHMgBr 2. H3O+ 7. concentration and the solvent used. and the more positive the proton. The amide I band is at 1630-1695 cm–1 and the amide II is at 1500-1560 cm–1. The range of chemical shifts are used because carboxylic acids undergo different amounts of hydrogen bonding based on structure of the acid. PBr3 4. PBr3 Br (h) CN 1. Mg . ether 5. Can you use proton NMR spectroscopy to distinguish these molecules? Why or why not? . and the more deshielded. we see both bands in the infrared. The amide I band is associated with the iminium unit (C=N) and the amide I with the carbonyl (C=O).2 pm 4 PPM 2 0 145. Do not attempt these problems until you have read and understood chapter 14.NaBH4 2. Me2CHCHO 6. H3O+ 3. O CO2Et IR: carbonyl at 1725 cm–1 IR: two bands at about NH2 1650 and 1540 cm–1 4 PPM 2 0 8 6 NMR shows OEt.O (g) 1. an ester.
Hexanoic acid will react to form the sodium salt.8 ppm 151. 158. 152. NMR: ketone shows two ethyl groups. 153.68–5. and the only peak past 1. N. whereas the ketone will show a strong C=O band at 1725 cm–1. The ester (ethyl butanoate) is insoluble in the aqueous medium and will not react with the bicarbonate.50 μ) and 1750 cm–1 (5. acids.00 μ) RCO2H Acid chlorides 1802 cm–1 (5. N.33–4. Using IR. the CN of the nitrile will show a moderate and sharp peak at 2210-2260 cm–1. which is soluble in water (it will dissolve). Add the unknown to a solution of aqueous sodium bicarbonate. 155. two bands at 1818 cm–1 (5.148. These are the peaks one should examine.3-2 ppm.6 ppm is the OH at about 3. 159. 160. C=O aldehydes. 157.N-Diethyl p-toluamide Methyl 2-methylpropanoate cis-Dimethyl maleate Triethyl phosphate: (EtO)3P=O 154.00 μ) and the OH at 2500–3000 cm–1 (3. The NMR shows three ethyl gorups. 156. The NMR should show a signal between 12-15 ppm for the COOH proton. so it will show up as an oil in the water.92 μ) 2500–3000 cm–1 (3. and a carbonyl at about 1725 cm–1. and two different CH2 resonate at about 2. IR: 1725 cm–1 for the C=O of the ketone. esters 1690–1760 cm–1 (5. but the alcohol will have a braod peak at about 3300 cm–1 O OH 3 2 PPM 1 0 4 2 PPM 0 150. The IR should show a broad band between 2500-300 cm–1.33–4.N-Dimethylbutanamide Diethyl phenylmalonate Diisobutyryl anhydride Isovaleryl chloride .55 μ) Anhydrides. there must be a focus on the carbonyl region.71 μ) 149. ketones. In the IR.
5-dipropylphenol OH N.5-dinitroanisole Cl O O OH (g) O C N OH N+ OO S (h) Cl Cl hexachlorobenzene OH (f) OH O phenetole Br I p-iodobenzenesulfonic acid O N+ OH 2-cyanobenzoic acid O N+ O(k) N C Br 4-bromo-3'-chlorobenzophenone (m) (l) m-xylene 2.2-dimethyl-4-phenylhexane 22.214.171.124-dinitrohydroquinone OH O (n) (p) N H N-acetyl-3-methylaniline 2.3-dichloro-5-methylbenzene .Chapter 21 79.5-trimethylbenzene O (e) Br 4-bromophthalic acid O O Cl (i) (j) O Cl O(d) Cl Cl Cl O (c) N+ 3.4-trimethylaniline Me 2-bromoisophthalic acid 1.2'-dimethylstilbene (E) o-bromobenzonitrile 2. O HO (a) (b) m-chlorophenol 1. NHMe Me (a) (b) HO2C Br CO2H (c) Cl Cl C3H7 (d) Me C3H7 2.
5-dinitrobenzoic acid 1-(2-bromophenyl)ethanone I OH (k) Me OH 5-iodobenzene-1.3-diol 5-ethyl-2-methylbenzonitrile Br OMe 1. O OCH3 Br (a) (b) Cl Br NO2 OCH3 NO2 (c) HN NO2 HN (d) O Br Br Br Br 82. OCH3 O (a) (b) Ph (c) OCH3 O O .CHO (e) F 3-fluorobenzaldehyde CN (i) Me (j) Et (f) NO2 CO2H (g) NO2 Br O (h) SO3H CN Et 3-cyano-4-ethylbenzenesulfonic acid NO2 Br (l) 3.2-dibromo-3-methylbenzene 1-methoxy-3-nitrobenzene 81.
Electron releasing substituents stabilize positive charge at the ipso carbon. O N H Cl 85. these are activating substituents in electrophilic aromatic substitution. HNO3 H2SO4 NO2 (a) . 86. Both OH and the carbon group of the ethyl unit are electron releasing. No mechanisms are provided.NO2 (d) (e) (f) O (no reaction) 83. Therefore. which accelerates the rate of the reaction. O OH CH CH NO SO H 2 3 2 3 NH2 H Cl NH2 CH3 H H Cl Cl NO2 H Cl 84. The major product or products are shown. which makes that intermediate more stable.
SOCl2 CN 3. 1-phenylhexane .NO2 (b) Br2 . benzene . heat 2. AlCl3 NO2 CH3 Me3CCl (h) AlCl3 OCH3 Cl OCH3 (g) NO2 Cl CH3 CMe3 H3C NO2 CMe3 . AlCl3 O C6H13 O OH 2. AlCl3 O Ph C6H13 (f) OCH3 Cl2 . H3O+ . AlCl3 NO2 Br CH3 O Cl AlCl3 OCH3 (d) Cl2 . FeCl3 OCH3 Cl H3CO CH3 O H3C C3H7 O C3H7 (c) Cl 1. oxalyl chloride (e) O 1.
OMe Cl Cl Cl OMe OMe OMe Cl OMe Cl Cl Cl Cl+ Cl Cl Cl 89. H2SO4 OH 87. and the rate of their formation is faster. The electron releasing capability of OMe is so great that the benzene ring will react without the need for a Lewis acid to generate X+. Mg . Br2 . which makes those intermediates lower in energy. so it will stabilize a positive charge on the ipso carbon to a greater extent. THF (i) 3. 3-methylcyclopentanone 4. The electron releasing groups stabilizes the positive charge on the ipso carbon in electrophilic aromatic substitution. Cl H Cl H Cl H Cl H 90. Br OH CH3 O NO2 88. . which gives it a large – dipole. AlCl3 2.1. The methoxy group is strongly electron releasing. The methyl group releasing electron to the oxygen. aq H+ SO3H (j) SO3 .
93. Therefore. The sulfur atom in sulfonic acid is more electrophilic and more positive than the carbon atom in acetic acid. benzene reacts more readily. OCH3 H (a) Br OCH3 H Br OCH3 H Br OCH3 H Br . NO2 Cl Cl Cl Cl NO2 O2N NO2 NO2 O2N NO2 Cl NO2 H2SO4 H+ OH 92.91. OH2 H – H+ Br AlCl3 E+Z 94. In addition. 95. the sulfur atom is larger and can accommodate another ligand more readily than carbon.
but it will be an ortho/para director. The C=C unit of another molecule of the diene is simply more reactive than the C=C unit of a benzene ring. 99. and a weaker activating substituent. Therefore. because the carbon group is electron releasing relative the C+ of an arenium ion. Reaction of the diene with the Lewis acid generates an allylic cation. but the real reason is that another resonance contributor can be drawn for the arenium ion. increasing the electron density and making it a stronger activating substituent. so a PhB group should be less electron releasing than an alkyl group. 98. 97. making it lower in electron density. Triphenylborane may undergo electrophilic aromatic substitution. It is not clear if the reaction will be autocatalytic. the diene reacts preferentially to form a polymer. The carbonyl unit of the ester in phenyl acetate will withdraw electron density from the oxygen atom. Anisole has an electron releasing methyl group on oxygen. This extra resonance contributor is not possible by reaction with methylbenzene. Boron is less electronegative than carbon. An alkyl substituent on benzene is activating. as shown. The -bond of the ethylene unit is more electron rich.OCH3 H (b) Br OCH3 H Br OCH3 H Br OCH3 H Br OCH3 O NH (c) H Br O OCH3 O NH H Br OCH3 O NH H Br OCH3 NH H Br H (d) Br H Br H Br 96. . phenyl acetate will react slower than anisole in a reaction with bromine and ferric bromide. Trisubstituted boron derivative are Lewis acids in their own right. but it should be slightly slower than a methyl group. Therefore.
H Br H Br H Br H Br 100. OCH3 O2N (a) NO2 NO2 (d) Br NO2 O HN O (g) HN (h) OCH3 (e) Cl Cl O NO2 NO2 NO2 OCH3 Cl CO2H (b) (c) HO3S NO2 (f) Cl OCH3 Cl OCH3 O SO3H CO2H O 101. which “holds" the electrophilic Br+ closer to the ortho carbon. O (b (c) (d) (e) NH2 (a) . 102. The oxygen atom of the OMe unit may coordinate to the Br+X– complex.
OH O– OH OH O O– O– O– O– . Electron transfer generates a radical anion. so the final product is cyclohexenone. and a second electron transfer leads to another carbocation. but the C=C unit isomerizes to form an enol. but electron transfer will occur so that the negative charge will not be on the carbon bearing the oxygen. which is more stable. A second hydrogen transfer leads to the alkoxide. Hydrogen transfer from the solvent leads to the radical. where the C=C units are connected (this is a conjugated system .CO2H (f) (g) (h) NH2 (i) NO2 (j) (k) N H O (l) O Cl (m) OBu (n) (o) CN 103.see chapter 23). Protonation in aqueous acid give the alcohol. The enol tautomerizes to the carbonyl.
then reaction at that carbon will be faster. and all such substitution products will be formed. and a * is shown to indicate the position of the positive charge for each resonance contributor. The Br is shown at each possible different position. (a) 22 -electrons aromatic (b) 6 -electrons aromatic (c) 6 -electrons aromatic (i) 4 -electrons not aromatic 10 -electrons aromatic (d) 4 -electrons not aromatic (e) (f) (g) 8 -electrons not aromatic (h) 4 -electrons 2 -electrons not aromatic aromatic (j) (k) (l) (m) 6 -electrons not aromatic 18 -electrons aromatic 20 -electrons not aromatic 30 -electrons aromatic (n) 18 -electrons aromatic (o) 14 -electrons aromatic 105. If reaction with Br+ places a positive charge on the ipso carbon in one of the resonance contributors. .104.
OMe * OMe * * * * * * * * H H Br OMe * OMe * * * * H Br * * * * * * * * H Br * * OMe * * * * * H * * * OMe * * * * * Br H OMe OMe * * * * Therefore * OMe * * * * OMe Br Br Br * * H * Br * * * Br * OMe OMe Br Br 106. which is another way of saying that the charge can be delocalized on the oxygen of OMe. and activating (reacts faster). . The OMe unit is electron releasing. Therefore. the ring bearing the OMe will react faster than the other ring. which of course occurs only in the ring bearing the OMe.
The arenium ion for attack at each carbon is shown. OCH3 OCH3 H Br OCH3 OCH3 Br OCH3 OCH3 H H H Br H Br OCH3 OCH3 Br OCH3 H H Br Br H Br 108. H Cl * attack via Cb * * * * * * * * 1 OMe * * * * * * * b * * * * * * * OMe 1 a attack via Ca * OMe * 1* * * * * Cl H OMe * Cl . which allows the charge to be delocalized on the oxygen. This is more stable than the arenium ion via Cb where the positive charge never appears on the ipso carbon. It is clear that attack via Ca leads to an arenium ion in which the positive charge is on the ipso carbon.107. Therefore. A * is used to show the position of the positive charge in each ion. the product resulting from reaction via Ca is preferred.
The major product or products are shown. FeBr3 Br NO2 acetyl chloride AlCl3 OMe Cl2 . AlCl3 Cl OMe NO2 Me Br2 .109. NH3 EtOH Me Me Me Me Me (f) . H2SO4 OMe NO2 NO2 (b) Br2 . AlCl3 NO2 Me Br OMe NO2 Me O OMe NO2 (c) O NO2 (d) (e) Br Me Me Na . OMe OMe (a) HNO3 . No mechanisms are provided.
FeBr3 (separate para Br product) NaNO2 . 112. Pd-C Me Br CuBr NO2 Br Me NH2 Me Br Br (c) aq. which is stabilizing. HNO3 NH2 F NO2 N2+BF4– H2SO4 (a) H2 . Give the major product of each of the following and show the intermediate product for each step. The nitro group at C4 will stabilize this charge whereas there is no resonance contributor where the negative charge appears at C3. because SO3 is a leaving group under these conditions. aq. HCl Me HNO3 HSO4 Me H2 . At elevated temperatures. This means that the reaction occurs via nucleophilic aromatic substitution. OH (a) (b) CN (c) Br (d) Cl I (e) (f) N=NPh (g) 111. One is that nucleophilic aromatic substitution places a negative charge in the ring after reaction with the benzene ring and not a positive charge such as is formed during electrophilic aromatic substitution. aq. Therefore. NaOH . Second. the nitro group is more stabilizing than the bromine. 113. HBF4 150°C Me (b) Br2 . HCl Br Br Br N2+Cl– Br 160°C . Pd-C NaNO2 . the bromine is polarizable so the if the negative charge is on the ipso carbon adjacent to a bromine. H2SO4 NHAc SO3H . 4-nitrophenol. HCl N2+ Cl– Br NH2 NaNO2 . with a negative charge in the intermediate. Br will take on a positive dipole. However. the hydroxide ion will attack the carbon bearing the sulfonate anion. which stabilizes the carbanion intermediate more than the bromine. the 4-nitrobenzenesulfonic acid will react faster to give the product. The nitro group is electron withdrawing.110. Remember two things.
NaNO2 . HCl N2+Cl– 160°C . H2SO4 NaNO2 . Pd-C NH2 N2+Cl– NaNO2 . aq. H2SO4 H2 . HCl O CuBr O NO2 N2+Cl– Br . THF MgI butanal OH PCC O O HNO3 . HCl 1-aminonaphthalene N I (f) Mg . THF SO3–Na+ 2R-iodopentane NO2 (e) HNO3 . H2SO4 SO3H NaH .NH2 (d) .
aq. via benzyne (a) NH2 NH2 (b) NH2 NH2 NH2 . 115. THF +Na–O S 3 OH cyclopentanone MeI MeO3S MeO3S MeO3S OH (a) (b) SO2OCH2CH=CH2 (c) CO2H NMe2 (d) NMe2 114. HCl 160°C . H2SO4 O2N Br NaH H2N Br –Cl+N 2 HO3S Br MgBr Mg . Pd-C Br Br NaNO2 . FeBr3 HNO3 H2SO4 Br H2 .Br (g) Br2 .
OMe Na . NH3. . EtOH OMe NO2 Na .OMe OMe (d) NH2 NH2 OEt NH2 OEt (c) NH2 (e) NH2 NH2 NH2 O 116. EtOH NO2 118. methyl cyclohexyl ether. NH3. CH3 O OH OH O OH O 117. There is only one.
4nitrobenzenediazonium chloride should react faster. It is essentially a nucleophilic aromatic substitution. PhCH2NH2. so a group such as nitro will stabilize the carbanion intermediate and an electron releasing group such as OMe will destabilize the intermediate. 124.3. In these reactions. Benzylamine. the leaving group is dinitrogen (N2). from the Ar-N2. 121. CO2 2. H3O+ CO2H EtOH H+ CO2Et LiAlH4 CH2OH 123. 122. Based on this analysis. CHO H2 tO2 CH2OH PBr3 CH2Br MeC C:– + EtOH H2 Lindlar . Br Mg MgBr 1. What products result form each reaction and what is the final product of the following sequence? (i) nitrobenzene + H2/Ni(R) gives aniline (ii) HCl/NaNO2 converts aniline to benzenediazonium chloride (iii) KF. fluorobenzene.5-trimethoxybenzene N OMe N N MeO 120. Me N2+OAc– Ph2NMe N N MeO 1. THF.119. This converts the diazonium salt to the final product.
in which water attacks the carbon bearing the diazonium salt.125. Since iodide is a better leaving group than chloride. (E)-1. which is rather acidic (pKa about 10). and this is a substitution reaction. 126. where it is assumed that iodobenzene will react faster than chlorobenzene. alkynes maybe reduced to the alkene (A) and the benzene ring may be reduced via Birch reduction to B. As phenol is formed.2-diphenylethene (trans-stilbene) SYNTHESIS. Do not attempt these problems until chapter 25 has been read and understood. 127. PhBr. Following proton transfer. Therefore at least two equivalents of NaOH are required: one to react with the chlorobenzene to form the phenol. . 130. If only one equivalent of NaOH is used. it will react with the NaOH to generate the phenoxide anion. However. The product formed by this reaction is phenol (PhOH). only about half of the chlorobenzene will react. loss of nitrogen leads to phenol. it is much moelkely that the alkyne anion will form faster via the acid-base reaction. the product is bromobenzene. N2+ NH2 NH2 128. Under these conditions. PhO–Na+. and the second will react with the phenol product. The mechanism is nucleophilic aromatic substitution. If the diazonium salt is heated with CuBr. Cl A Cl B Cl Cl 129.
SO3 . FeBr3 2. Br2 . No mechanisms are provided. FeBr3 2. NaBH4 2. Br 1.HNO3/H2SO4 2. AlCl3 3. NaH then EtI 1. The major product or products are given. Cl2 . Pd 4. H2 . AlCl3 3.Br Br2 FeBr3 Br propanoyl chloride AlCl3 Br 1. H2 . Br2 .HNO3/H2SO4 2. aq. Pd 4. 150°C (a) Cl OEt (b) Br F (c) Br SO3H (d) 1. H3O+ . Br2 . H2SO4 seaprate ortho Br . AlCl3 (separate ortho) 1. NH4Cl HO Br O PBr3 separate out the ortho product Br 131. 132. HONO 5. Br2 . HBF4 . NaNO2 5. heat 6.
H2 . H3O+ 4. HBF4 . H2SO4 3. H2 . HNO3 . H2SO4 2. Pd 4. HONO 6. Pd 5. H2SO4 3. NaNO2 6. Br2 . propanoyl chloride. H2 . HNO3 . butanoyl chloride AlCl3 2. HONO 9. CuCN 7. MeMgBr . Pd 5. 150°C 1. H3O+ 4. heat 1. Me2CHMgBr 3. AlCl3 3. HONO 6. HNO3 . H3O+ . H3O+ 8. propanoyl chloride AlCl3 2. HNO3 .(e) 1. CuBr Br F OH CH2CH2CH2CH3 (f) OH OH (g) CN (h) Br (i) . KOH 4. Pd 3. H2SO4 2. N2H4 . Ac2O 4. Br3 5. H2SO4 (separate ortho) 5. EtOH 1. HNO3 . AlCl3 2. H3O+ . HONO 5. H2 . heat 1. KOH .
150°C O NO2 (b) 1. 2S-bromobutane Br CN (d) 1. LiAlH4 . NaH . N2H4 . Syntheses are shown for each compound from a selected starting material. AlCl3 2. H3 . AlCl3 2. H2 . H2SO4 2. PBr3 4. Me3CBr . 150°C CO2Me (c) 1. Pd 3. HNO3 . H2 . H2 . Br2 . H3O+ 6. THF 4. NaNO2 4. Do not attempt these problems until chapter 14 has been read and understood.133. H3O+ O (f) 1. HBF4 . . HONO 5. HNO3 . EtI NH2 Cl F (R) O OH OEt Spectroscopic problems. H+ NHAc (e) 1. H2SO4 2. HONO 5. THF 5. Pd (a) 3. H3O+ 3. H2O 3. NaNO2 4. NaH 7. Cl2 . LiAlH4 . AlCl3 3. KOH 3. H2SO4 2. NaN3 . HBF4 . F O 1.CH2=CHCH2MgBr 2. HNO3 . aq. H3PO2 6. Pd 4.Pd 4.
Benzonitrile is the expected product. The aromatic region for methylnaphthalene will integrate to nine protons. respectively 137. 4-Methylanisole is more symmetrical and will have only two identical signals. OCH3 Little diffrence in NMR IR: phenol OH at 3300 cm–1 is broader and more intense OH OCH3 8 6 4 PPM 2 0 8 6 4 PPM 2 0 136. Aniline will have amine NH at about 3300 cm–1. and since it is a primary mine.NH2 134. there will be two peaks (a doublet). The only real difference is in the aromatic region of the NMR. . whereas the aromatic region of toluene will integrate to five. Benzonitrile will have the nitrile peak at about 2260 cm–1 whereas benzamide will have the amide I and amide II peaks at 1630-1695 and 1500-1560 cm–1. whereas aniline is insoluble in aqueous NaOH. whereas 2-methylanisole has more signals and the aromatic region is a bit more complex. N-Acetylaniline will have one peak in the NH region. Phenol is soluble is aqueous NaOH because phenol is acidic (pKa. relative to the three proton singlet for the methyl group. as shown.. The only discernable difference is in the infrared. 10). 135. O CN NH2 8 6 4 PPM 2 0 8 6 4 PPM 2 0 138. but will have the amide I and amide II peaks at 1630-1695 and 1500-1560 cm–1. about 7 ppm.
3. 4-Isobutyl benzaldehyde Hexaethylbenzene tert-Butyl-4-methylphenol 4-Isopropyl-phenetole 1.4-Dichlorobenzene N-Ethyl aniline . 140. 142.5-Triethylbenzene 4-Methylphenol 1. so there will be NO signals in the proton NMR. 141. 145. 144.139. 143. 146. There are no protons. 147.
Chapter 22 O Ph O Ph O pKa . 19 78. O O O O O O > N > N > N C C N C C N C C N 81. Because these are kinetic control conditions. 79. and hydrolysis will simply protonate the enolate anion to regenerate the original ketone. The reaction with LDA generates the kinetic enolate. The enolate stabilized by two adjacent carbonyl groups is more stable than the enolate anion stabilized by only one carbonyl. so the enolate anion will react to regenerate the ketone. which is electron releasing. . These are thermodynamic conditions. pKa . which make it even more acidic. The nitro group is more electron withdrawing and the charge can be delocalized on the nitro group. the stereochemistry at the adjacent methyl group is not affected. will provide further stabilization to each enolate anion. The presence of the methyl group. 20-21 no -proton O 77. pKa = 11. which makes acetonitrile less acidic (pKa. 82. 80. 19-20 pKa . 24). Ammonia is a protic solvent. The carbon of the cyano group is +. Aprotic solvents are compatible with kinetic control conditions and protic solvents are compatible with thermodynamic control conditions. The pKa of acetone is about 19. protic protic protic protic O O NH3 Me2NH MeOH O O OH OEt aprotic aprotic aprotic 83.
THF . dilute aq H+ O CH3 H OTs H OTs Ph OH O O O O OH (R) O O 84. LDA . –78°C 2.H O CH3 H 1. 85. O (a) N Li O O N Li+ O O N N H H (b) O (c) Li-NH2 O (d) Li O Li+ NH3 Li+ O NaH Na+ H-H .
Kinetic conditions are preferred.O (a) (b) O H (c) O H O (d) (e) Ph H H (f) O H Ph Ph H 86. which is a much weaker acid than the ketone. there is unreacted aldehyde in the equilibrium. 87. The aprotic solvent THF does not have an acidic proton to react with the enolate anion. but under equilibration conditions (thermodynamic). 89. The short reaction time does not give the reaction time to equilibrate: reaction of the strong base and the ketone is rapid but reaction of the enolate anion with the weak acid (the amine) is slow. The same enolate anion is generated by either set of conditions. The low reaction temperature allows the forward reaction to occur. This combination favors the forward reaction but not the reverse (Ka is larger). The Me2NLi is a strong base that generates Me2NH as the conjugate acid. H O O O O (b) H kinetic & thermodynamic since only one enolate anion is possible O O (d) (a) kinetic O (c) kinetic thermodynamic O Ph kinetic Ph thermodynamic Ph Ph (e) kinetic O O thermodynamic (f) O kinetic & thermodynamic since only one enolate anion is possible 88. which also favors a larger Ka. which may react in an aldol condensation of the aldehyde and the enolate anion (self-condensation). but provides less energy to overcome the activation barrier for the reverse reaction. These are kinetic control conditions. .
80°C O 2. hydrolysis (f) O 1. 4-ethyl-2-methyl-3-heptanone 3. NaOEt . hydrolysis OH O Ph HO OH O (e) 1. which means that a base will NOT remove the aldehyde proton. -78°C 2. It does not form. hydrolysis OH O . cyclopentanone 3.Under kinetic control conditions. which is normally polarized +C=O –. NaOEt . 90. hydrolysis HO 1. the aldehyde is effectively converted entirely to the enolate anion. reflux 2. -78°C 2. and such a carbocation is not resonance stabilized and is indeed very high in energy. O O (a) 1. KOt-Bu. THF . LDA . Removal of the aldehyde proton laces a negative charge on the carbonyl carbon. t-BuOH . Removal of the -proton generates a resonance stabilized enolate anion. THF . so there is little chance of self condensation (self condensation is minimized). 3-phenylpentanal HO Ph CHO O (b) O (c) CHO 3. LDA . cyclopentanone 3. -78°C 2. reflux 2. The aldol condensation products for each reaction is shown. hydrolysis O (d) Ph 1. EtOH . ether . LDA . hydrolysis 1. EtOH . 91.
Benzaldehyde does not have an -proton. Under these thermodynamic conditions. reflux 2-hexanone 2. so formation of an enolate anion is impossible. O O (a) O (b) 1. treating the aldehyde with LDA in THF at –78°C. hydrolysis OH CHO OH . 94. kinetic control conditions must be used. hydrolysis O OH 92. -78°C 2. EtOH. and then adding the hexanal. heat OHC CHO 2. hydrolysis 1. EtOH . LDA . THF –78°C 2. LiN(iPr)2 . hydrolysis +other aldols OH O (h) 1. hexanal HO CHO CHO 95. -78°C 2. EtOH reflux CHO 2. 3. and it will react with benzaldehyde because the aldehyde is more reactive to acyl addition than a ketone. The only enolate anion that can be formed is from benzophenone. 2-hexanone 3.O (g) O 1. CHO 1. LDA . the enolate anion from pentanal with react with itself in a self condensation to give the aldol product shown. hexanal HO 1. so reaction with lithium diisopropylamide will be rather slow.5-Diethyl-4-heptanone has a great deal of steric hindrance at the -carbon atoms. particularly at the low temperature. NaOEt . To obtain the mixed aldol. THF . THF . 93. NaOEt . NaOEt.
LDA . -78°C 2. EtOH . THF . -78°C OH Ph 96.3-diketone unit. O O Me Me Me O O 1. LDA . Reaction with LDA generates the enolate anion from the 1. hydrolysis HO CHO O (d) Ph CHO 2. Under thermodynamic control the more substituted enolate anion will be formed. THF . . Sodium methoxide can react with the ethyl ester to form the methyl ester. reflux Me 2. NaOEt . LDA . Intramolecular aldol condensation generates a six-membered ring as shown. as shown. THF O O O OH H3 O+ O O O O O 97. and subsequent internal aldol condensation will form the six-membered ring with the distal carbon rather than the fourmembered ring from reaction with the closest carbonyl. hydrolysis 1. because that is the more acidic proton. The expected Claisen product is the keto ethyl ester.O O (c) O 1. hydrolysis Me Me O OH Me Me 98. but the keto methyl ester can also form if the methyl ester is generated as suggested.
-78°C CHO 2. LDA . 100. LDA .O OEt O OEt O O OMe OMe O O EtO2C (a) CO2Et (b) Ph EtO2C O MeO2C (c) CO2Me (d) O Ph CO2Et HO CO2Et CO2Et CO2Et (e) O CO2Et (f) O CO2Et O (g) HO2C Ph 99. THF . THF . mild hydrolysis H H ketone is more acidic than the ester CHO ketone is more acidic than the ester . CO2Et O O (a) CO2Et 1. -78°C 2. mild hydrolysis O O H (b) H CO2Et 1.
reflux CO2Et (a) 2. hydrolysis O (b) CO2Me 1. hydrolysis 1. NaOEt . -78°C 2. EtOH . reflux Me3C-CO2Et 2. EtOH . -78°C CO2Et 2.(c) EtO2C CHO 1. THF . EtOH . NaOEt . hydrolysis CO2Me O 1. -78°C 2. only starting materials 3. LDA . The product or products are shown. and formation of 6-membered ring is energetically more facile than forming a 9-membered ring 101. hydrolysis (d) CO2Et CO2Et (e) 1. NaOEt . reflux ethyl 3-phenylpropanoate 2. LDA . CO2Et 1. LDA . hydrolysis Ph CO2Et O CO2Et O OEt Ph O Ph O Ph O . mild hydrolysis CO2Et O CHO aldehyde -H is most acidic. THF . THF . 2-methyl-4-octanone (c) CO2Et CO2Et OH CO2Et no new products. No mechanisms are provided. methyl pentanoate 3.
EtOH. -78°C 2. hydrolysis 1. vigorous hydrolysis (c) CHO OHC HO 1. NEt3 3. -78°C CO2Me CO2Et (g) CO2H 3.(f) CO2H 1. vigorous hydrolysis CHO (d) CHO O . MeOH . LDA. NaOEt. LDA.r eflux 2. THF. EtOH. DCC . vigorous hydrolysis Ph 1. reflux. LDA . No mechanisms are provided. THF. 2 eq. NaOEt . PhCHO O CO2H (b) CO2Et 2. excess MeOH . The major product or products are shown. ethyl 2-methylbutanoate (a) O 3. -78°C 2. NaOEt. ethyl cyclopentanecarboxylate 4. EtOH . EtOH 2. THF . 2-pentanone 3. reflux 4. O 1. reflux 2. hydrolysis O CO2H 1. hydrolysis EtO2C 102. SOCl2 2. NaOMe . hydrolysis O O (h) CO2Et CO2Et 1.
CH3 O (a) Ph (d) Br Ph P 3 Ph (b) (c) Bu O (e) OEt (g) PPh3 OH (f) . 6N HCl CHO O (f) O O (a) PPh3+ Br– (b) PPh3+ Br– (c) Ph3P (d) (e) P I (f) PPh3 103. ethyl butanoate 3. vigorous hydrolysis CHO 1. LDA. -78°C 2. THF. -78°C 2. LDA. 104. THF.CHO (e) 1.
so there will be only one site for generation of an ylid. Diphenylphosphine will react with two equivalents of an alkyl halide. O H O H . Triphenylphosphine can react with only one equivalent of an alkyl halide. If the carbonyl oxygen attacks the acidic proton. SMe2 Br SMe2 Br SMe2 SMe2 Br O SMe2 O O + Me2S 107. which is very high in energy and does not form under most thermolysis conditions. electron transfer must dump electrons on carbon to form a carbanion. 109. (a) O PPh3 O PPh3 (b) O PPh3 O PPh3 (c) O PPh3 O PPh3 (d) O PPh3 O PPh3 106. O Br O O O O 108. aq. LDA . THF . so there will be two sites for generation of an ylid. OsO4 t-BuOOH OH 2 PDC OH O 1. The lack of a stable product O means there is no place to “dump” the electrons if CO2 departs.105. and the energy requirements for this reaction are such that it does not occur. –78°C 2.
H2O Ph CO2H CO2H 110. but high temperatures are required. 111. The -bonds of the benzene ring may react a weak base.CO2H CO2H N Ph CO2H CO2H PhCHO CO2H N CO2H N CO2– HN CO2H H O HO Ph CO2– CO2H H3O+ Ph H H CO2– HN CO2H O Ph CO2– HN CO2H H2O Ph CO2H CO2H . this one is resonance stabilized. Loss of a hydrogen atom from the intermediate leads to benzene. CH(CN)2 . and loss of carbon dioxide generates a carbanion. O O H .O=C=O H H O CH2(CN)2 NaOEt EtOH O –CH(CN) 2 H Ph H H3O+ Ph H OH Ph CH(CN)2 112. Although carbanions are difficult to form. so the energy requirements are feasible.
which will facilitate dehydration. The enolate anion is a base as well as a nucleophile. The product from the kinetic enolate anion. but reaction as a base with the alkyl halide leads to the alkene via an E2 reaction. does have a hydrogen and elimination proceeds as shown. Reaction as a nucleophile gives the calculated product. This means that the proton is rather acidic and will be removed with a relatively weak base such as carbonate. NC NC O LDA NC NC O NC CN OH NC H3 O+ CN OH 114. with three resonance contributors. The thermodynamic enolate anion leads to a product in which there is no -hydrogen atom. O O– O no -hydrogen. so Ph no elimination Ph Ph OH Ph O– O O Ph Ph O HO Ph Ph Ph Ph 115. It is likely that dehydration is very facile because the C=C unit will be conjugated to the two electron withdrawing nitro groups. OH O2N CHO + O2N Na2CO3 H3O NO 2 O2N O2N O O O N N O O O O N N O O O O N N O NO2 116. The carbanion derived from dinitromethane is extensively delocalized due to the nitro groups. A mixture of E and Z isomers are formed because the -carbon of the alkyl halide is not chiral.113. The stability of this carbanion makes deprotonation very facile. so elimination is not possible. however. .
O Br (R) (S) O– E2 (E) (Z) SYNTHESIS. Do not attempt these problems until chapter 25 has been read and understood. . O (a) H O (b) H H (c) O Ph3P=CH2CH3 (E) (E) Ph3P=CH2 Ph3P O (d) H (e) O Ph3P=CH2 Ph3P=CHCH2Ph (E) Ph Ph3P (f) O (E) 117.
EtOH . –78°C O 2. 2-methylbutanal 4. LDA . SOCl2 9. LDA . LDA . PCC 5. EtI 4. PhCH=PPh3 H3O+ CN O Ph (f) CO2Et Spectroscopy Problems. LDA . NaH 5. pentanal 3. aq. H+ O CO2H (e) CN 1. THF . aq. methyl butnoate (a) O O O O 1. 2. A synthesis is shown for each disconnection. –78°C 2. Me2CHCH2Br 6. NaH 3. Do not attempt these problems until chapter 14 has been read and understood. H+ 2. H3O+ 7. Et2CuLi 4. –78°C 2. CHO O (a) (b) OH (c) O CO2Et (d) O Ph 119. H+ 2. THF . THF .118. THF . . NH3 O (c) CH2(CO2H)2 NH2 (d) CO2H 1. 200°C 8. PCC 1. 3-pentanone (b) 3. H+ OH 1. –78°C 3. excess EtOH . SOCl2 3. 1.
The band at about 3340 cm-1 is likely due to the O-H absorption of the tertiary alcohol product. The imine is likely difficult to isolate. whereas the ketone will show a strong band at 1725 cm–1.120. H+ HO CO2Et CO2Et . The lack of a signal at 2600 cm-1 indicates it is not an acid. The carbon of a ketone and an ester are very similar. whereas an ethyl ester will show a quartet at about 3. CO2Et CO2Et Ph CO2Et 1. LDA 2. A nitrile will show a medium band at 2220 cm–1 in the IR. It really depends on the position of the keto units and the ester group. which will be lacking for the diketone.5 ppm. so it is unlikely this can be used to distinguish them. it is likely that the initially formed alcohol lost a molecule of water via dehydration to give the alkene shown. PhCHO Ph CO2Et 2. The IR will show no difference. O– O OH 124. 121. 3 2 PPM 1 0 CN NH O 3 2 PPM 1 0 3 2 PPM 1 0 123. Therefore. but imines show a band at about 1660 cm–1 for the C=N unit. There is little difference in the NMR.5 ppm. but the NMR for a methyl ester will show a single that integrates the 3H at about 3. and the signal at about 1670 cm-1 indicates the presence of a C=C-C=O unit.6 ppm that integrates to 2H and a triplet at about 1. as that will determine the chemical shift and multiplicity in the NMR. dilure aq. 122. The most reasonable difference is the OCH signal of the methyl ester.2 ppm that integrates to 3H. at about 3.
125. HO Ph IR: broad peak at 3300 cm–1 for O-H mass spectrum: weak or absent M. but a significant M-18 peak. 8 6 4 PPM 2 0 150 100 PPM 50 0 .5 ppm. The prominent COOH signal in the IR and the presence of an methyl group in the proton NMR are the most salient feature. The acid will not have the methyl group at 3. but will have a COOH signal around 12 ppm. There is an extra carbon atom in the carbon NMR IR: 1725 cm-1 IR: 1725 cm–1 O O and broad band CO2Me CO2H 2500-3000 cm–1 13C 200 100 PPM 0 200 100 PPM 0 1H 4 2 PPM 0 10 PPM 5 0 126.
O little difference in the IR O 3 2 PPM 1 0 3 2 the presence of the propyl group is obvious in the NMR PPM 1 0 129. 132. 2.127.5-Hexanedione Methylenecyclopentane Ethyl 3-oxopentanoate 4-Hydroxy-4-methyl-2-pentanone . 133.8 128. Ph kinetic O Ph very little difference in the infrared O thermodynamic 8 6 4 PPM 2 0 8 6 4 PPM 2 0 ethyl gorup two methyl groups + CH at about 2. 131.
CO2H CO2H A O E OH CO2Et CO2Et B CO2Et CO2Et CO2H CO2H C D 135.A B OH C O O D O– 134. E CO2H .
3-butadiene (g) 3E.3.Chapter 23 40.5-cyclooctadiene (h) 1. HC C-C C-CH3.4.4E-hexadiene 2Z. 43.4E-isomer.4-diphenyl-1E.3-dimethyl-1.3E-butadiene (i) 2.2-diethylcyclohexadiene H (f) O 2. (a) (b) (c) hex-1-en-3-yne (d) 2E.5-tetramethyl-2.5E-dodecadienal 1.4Z-hexadiene 42. The methyl groups are far apart in the 2E. so S-cis and S-trans isomers are not possible. .4Z diene has severe steric interactions for the methyl groups that raises the energy of the conformation. 2E.7-diethylcyclohept-2-en-1-one O (d) No! The alkyne units are linear. It is clear from the structures that the cisoid conformation of the 2Z.4Z isomer.4-pentadienoic acid 1.5Z-nonadiene O (e) OH 2.4-hexadiene 41. O (a) (b) O ethyl benzoate hex-3E-en-2-one O NC (c) pent-2-ynenitrile 2. which makes this conformation lower in energy relative to the cisoid conformation of the 2Z.
5-dione O (k) penta-1. and can deliver hydride to the C=C unit by an intramolecular reaction. The reason for reactivity at both sites is bond polarization of the C=O. The oxygen atom is more basic than the p-bond of an alkene. The allylic cation intermediate is more stable. which are not resonance stabilized H H H O O O O O or 46. Briefly explain why an acid catalyst reacts with the carbonyl oxygen of methyl vinyl ketone. This is clear when examining the oxocarbenium ion via protonation of the carbonyl. leading to a + on the carbonyl carbon and also the terminal carbon of the C=C unit.O (e) H acrolein (f) O (g) O O O O O dimethyl fumarate O O hexa-3E-en-2. which extends through the C=C unit by vinylogy. but it can also deliver hydride to the carbonyl carbon. Draw the resultant intermediate. H H H Al H – Li + O – + 45.5-diphenyl-1-pentene (l) O O (m) OH cyclopent-3-en-1-one acrylic acid (j) 2-methylhex-1-en-3-one O (n) OH (o) 44. Protonation of the C=C unit will generate the unstable carbocations shown.4-dien-3-one H O oct-4Z-enal cyclohexene-1-carboxylic acid (h) methyl vinyl ketone (i) 1. and the conjugated ketone is more stable than the nonconjugated ketone. . Lithium aluminum hydride coordinates to the carbonyl oxygen. which is resonance stabilized as shown.
= 1545 Å. calculate .47x104 cm-1 48.5 nm.05 kcal.05 kcal. = 5. O (a) methyl vinyl ketone (b) 3-hexanone weak-non-conjugated O (c) CHO benzaldehyde strong-conjugated cyclohex-2-en-1-one strong-conjugated (d) O .25x104 cm-1 (f) 185 kcal = 154.9x104 cm-1 (b) 16x102 cm-1 =19. NH3 EtOH OMe H3 O+ O heat O Me 1. = log( Io )/cd = (4. = 5.OMe Na. (a) 345 nm = 82.67x103 nm (e) 8000 Å =35.87 kcal.25x103 nm 3 (c) 1765 cm-1 = 5.2 g/mL and the pathlength is 5 dm.MeOH O Me H2O H2O O Me OMe H+ -H+ HO O O OH -H+ O 47.2 H-shift to more stable allklic cation Me H+ H HO Me . = 5. If Io I I = c = 1.5x10) = 190000 49.5 g/mL (10 dm pathlength). = 6.67x10 nm.95x10–10 I 50. If = 38000 for c = 0.7 kcal. calculate log Io = x c x d = (38000)(0.77x10–9)/(1.14 kJ.2)(5) = 7. = 2. = 1.67x104 Å (d) 325 kJ =5. = 6.
(a) HCl . No mechanisms are provided. The major product or products are shown. O O (a) 215+12+12 = 239 nm O (b) H 210 + 30+12 = 252 nm H C (e) (f) C (g) 214+30+30+30 = 304 nm 253+5+5 = 263 nm 214+5+30 = 249 nm (no value is given for C C.O (e) 1. 214+5+5+5 = 229 nm 210+10+12 = 232 nm (c) (d) H 52.3-cyclohexadiene strong-conjugated OH (h) (i) (g) O ethyl hex-2-enoate strong-conjugated styrene strong-conjugated hex-3-en-2-ol weak-non-conjugated 51. 60°C Cl I . so estimate with C=C value).6.5-heptadiene weak-non-conjugated (f) 1. -80°C I (b) I2 . The predicted maximum UV absorption peak for each is shown using Figure 23.
HCl aqueous acetone HO (e) OH (f) HCl . The product will be the chloride shown. which may be difficult to form due to the proximity of the + and +. the bromide ion will attack the bromonium ion to give the dibromide. 54. -90°C Br HBr –80°C Br 53. 40°C (d) cat.Br (c) HBr . Reaction with diatomic bromine give a bromonium ion. 50°C Cl (g) HBr . Reaction with HCl at the acyl carbon is reversible. and formation of the carbocation next to the + carbonyl carbon is energetically unfavorable. 50°C Cl HCl . . but if it forms.
The major product or products are shown. -10°C 2.+ Cl O Br O further from +. THF 2. so this is lower in energy Br Br O Br– + O O + O two proximal positive charges are very destabilizing Me (a) n CO2Et (d) n (e) Me (b) n CO2Et Me n CHO (f) (c) Cl Ph n 55. ether 2. ether 2. THF . hydrolysis Ph OH Me OH Me O Ph 1. No mechanisms are provided. hydrolysis CHO 1. hyrolysis minor CHO Ph Ph O (d) 1. PhMgBr . hydrolysis Li OH Bu . (a) O (b) Ph CHO (c) 1. Ph2CuLi . MeMgBr . Me n CN 56.
hydrolysis (e) 57. (a) O (b) Br O H O (d) O H2 . The major product or products for each reaction sequence are shown. –20°C O (c) . Pd O O NaBH4 OH Ph2CuLi no reaction (N. O O (a) O (b) O HO O (c) O HO O O OH O OH O 58.O 1. ether OH Me 2.R. MeMgBr .) Br Br2 .
R. Neither the 1. The only UV active compound is the starting material.2- . Pd (g) (h) O (i) O NaBH4 OH 1. this is a trick question.4-byproduct have a conjugated chromophore that will give a significant absorption in the UV. 60. Me O O HO Me 1.O (e) LiAlH4 OH + OH (f) LiAlH4 no reaction (N. In a sense.4- 1. Ph3P=CH2 2. H2 .2. NMR is a far better probe to distinguish these products.nor the 1.) H2 . Pd O O HO O O O O HO HO O 59.
In consultation with your instructor. In both cases. Ph (E) Ph (Z) N (a) O O O O (b) n (c) N C n C 62. the major rotamer is the s-trans because it will have the lowest energy when compared to the s-cis rotamer. Retrosyntheses are shown. (a) OMe HO O O HO CHO O HO HO HO (b) Br OH O O .61. suggest a synthesis based on the retrosynthesis. understood. n Do not attempt these problems until Chapter 25 has been read and 63. Synthesis Problems.
reflux Ph O Ph O 2. EtOH . THF 2. H2 . Pd-C . succinic acid. PCC 2. SOCl2 3. PBr3 Br (a) 4. benzene . LDA . cyclohexanone 3. H3O+ 3. –78°C 2. SOCl2 5. AlCl3 O 1. KOH . Show a synthesis for each of the following molecules from the designated starting material. PhCH2Br 3. H2SO4 2.NaOEt . Mg . Ph3P=CMe2 (b) O 1.(c) Ph NH2 Ph CN Ph CO2H Ph OH Ph Ph O Cl O OH O 64. EtOH OH 1. H3O+ OEt 4. THF . 1. AlCl3 O (c) O (d) O (e) 1.
4-bromo-1-butene CO2H 4. whereas the conjugated carbonyl will be at about 1695 cm–1. NaOH. so no strong UV peaks 3 alkene H + no methyl on C=C 2 0 6 4 PPM 2 0 8 6 4 PPM 200 100 PPM 0 200 two methyl signals no methyelne one methyl and one methylene 100 PPM 0 66. H+ Ph HO2C Ph Spectroscopic problems. Do not attempt these problems until Chapter 14 has been read and understood 65. The carbonyl for the non-conjugated ketone will be at about 1725 cm–1 in the IR. NaH . 1. aq.4-dintirophenylhydrazine will give a yellow solid when it reacts with the non-conjugated ketone but an orange-red solid when it reacts with the conjugated ketone.3-Hexadiene is conjugated and will be UV active. The proton and carbon NMR for the conjugated ketone will show protons and carbon in the C=C region. H+ 2. The conjugated diene will react with bromine to give 1. 67.5-hexadiene is non-conjugated and will show no significant UV activity. EtOH . whereas pent-3-en-2-one is conjugated and will show a strong band in the UV. O conjugated and UV active O pent-3-en-2-one 2 alkene H + methyl on C=C (doublet) pent-4-en-2-one non-conjugated. whereas 1. aq. whereas the non-conjugated diene will show that each alkene reacts independently. THF 3. Reaction with a solution of 2.4 products. . and the non-conjugated ketone will not.2 and 1. 68.Ph (f) Ph 1. 2-Pentanone is not conjugated and will not show bands in the UV.
IR is is same. 73. 72. trans-1. 71.4-Diphenyl-1.3-Pentadiene 1.3-butadiene trans-3-Hepten-2-one Ethyl methacrylate 4-Pentenoic acid . 70.Br Br Br Both are not conjugated so there is no UV. with a C=C peak at about 1650 cm–1 Br 6 4 PPM 2 0 6 4 PPM 2 0 more symmetrical 69.
CO2Et CO2Et OMe EtO2C 27. can form a substituted furan derivative by loss of ethene. In addition. so the activation energy for the Diels-Alder reaction will be higher and it will be slower. requiring harsher reaction conditions. as shown. Both of these phenomena work to make the rearrangement of B much slower than A. A diene must be conjugated and able to achieve a s-cis (cisoid) conformation. The circled alkene has an electron releasing group. CO2Et CO2Et OMe EtO2C 26. This is known as a “retro-Diels-Alder” and occurs at a higher temperature than what is usually required for the initial Diels-Alder reaction. steric repulsion of the methyl groups inhibits close approach the two carbons. A O B O 28. the initial Diels-Alder product.Chapter 24 24. which lowers the LUMO of the C=C more than any other choice. which now has another C=C unit. When heated. The circled alkene has two electron withdrawing groups. locked in transoid not conjugated 25. so the activation energy for the Diels-Alder reaction will be lower and it will proceed faster and under milder conditions. In is clear in B that both the attacking carbon and the recipient carbon are much more sterically hindered than in A. This rearrangement occurs via attack of the -bond of one alkene unit at the terminal carbon of the other C=C unit. . which raises the LUMO energy of the C=C more than any other choice.
and this combination makes cyclopentadiene much more reactive. Relief of strain accelerates the rate of the reaction relative to the reaction of B. Confining the -bonds to the ring also makes the -electrons more available for donation. which is lacking in the product. 30. O (a) + O O CHO heat heat O O O O O CHO O (b) + CO2Et (c) + EtO2C heat CO2Et CO2Et CO2Et CO2Et . A B 31. Cyclopentadiene is locked into a s-cis conformation since it is part of a five-membered ring. Pd CO2Me CO2Me CO2Me CO2Me 29. Molecule A reacts faster because the Cope rearrangement relieves the strain of the three-membered ring. where there is no strain.CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me H2 . Give the major product for each of the following reactions.
. The electron withdrawing carbonyl group lowers the energy of the LUMO for the C=C unit. OEt Me EtO Me 36. Addition of BF3 to the Diels-Alder reaction of acrolein and 1. 33. but Diels-Alder reactions with dienes is very slow and requires high temperatures (a) locked in traansoid. but it will be slow. The major product for each is shown. There are two electron releasing alkoxy groups that raise the LUMO of the alkene to a level that the activation energy is simply too high to occur at low temperatures. This energy lowering makes the energy gap between the LUMO (alkene) and the HOMO (diene) smaller. cannot undergo a Diels-Alder reaction (b) (d) Reacts as an alkene. which indicates a lower activation energy and a faster reaction. and lowers the LUMO energy even more. but Diels-Alder reactions with dienes is very slow and requires high temperatures (c) too sterically hindered.3-butadiene leads to coordination of the Lewis acid with the aldehyde. Reacts as an alkene. This lowering of the LUMO energy leads to a lower activation energy and a faster reaction. 35. relative to ethene. 34.(d) + CN heat CN (e) + CO2Et heat CO2Et 32. DielsAlder is possible. which withdraws more electron density from the C=C unit.
The major product for each reaction is shown.(a) O (b) heat heat O (c) O heat O O 37. OMe OMe (a) ethyl acrylate heat CO2Et Me (b) Ph maleic anhydride heat acrylonitrile heat CN Ph O O O (c) Ph Me (d) Me diethyl fumarate heat Ph Me CO2Et Me CO2Et .
(E) CO2Et CO2Et EtO2C Ph Ph CO2Et Ph .O (e) methyl vinyl ketone heat Me methyl acrylate heat CO2Me (f) Me disrotatory (E) conrotatory CO2Et (a) CO2Et CO2Et (E) (b) CO2Et (E) CO2Et CO2Et (Z) Ph (c) CO2Et CO2Et (E) CO2Et CO2Et CO2Et CO2Et (E) CO2Et (d) CO2Et 38.
so the circled diastereomer will be the major product. The Diels-Alder reaction proceeds via an endo transition state. H O (a) heat O (b) OH (c) heat heat OH O H (d) O heat O . The major product is shown for each reaction.39. CO2Et CO2Et CO2Et CO2Et CO2Et all are racemic. which is impossible since the cisstereochemistry of diethyl maleate is retained. so there is greater secondary orbital interactions for the diester relative to the mono-ester. so each has an enantiomer CO2Et CO2Et CO2Et CO2Et CO2Et 40. which accounts for only eight of the total 24 = 16 stereoisomers. The remainder of the possible stereoisomers have a trans-relationship for the diester. There are two carbonyl units. Note that all of the diastereomers are racemic. 41. with a disrotatory motion of the methyl groups.
35°C >130°C Synthesis Problems. a retro Diels-Alder reaction occurs to regenerate two equivalents of cyclopentadiene. Pd-C 3. THF. Ph Ph Ph Ph OSiMe3 O 1. Ph3P=CMe2 . Me3SiCl 3. which is on the right. The diene on the right has a phenyl substituent on each C=C unit. This means that the Cope rearrangement generates a new diene with more substituted alkene units. LDA. which are more stable than the monosubstituted alkene units of the diene on the left.42. A synthetic scheme is provided for each problem. H2 . the equilibrium will favor formation of the more stable diene. 46. -78°C 2. Cyclopentadiene reacts with another molecule of cyclopentadiene at low temperature. (a) 1. so the DielsAlder product shown is what is in a bottle of commercial cyclopentadiene. Do not attempt these problems until chapter 25 is read and understood. one can use the cyclopentadiene in other reactions. Since this is an equilibrium process. H OH heat OH H H OH H O 45. If kept cold. methyl vinyl ketone 2. If this dimeric compound is heated. 44. heat O OSiMe3 H3O+ O OH 43.
SOCl2 6. heat 2. –78°C 4.(b) 1. heat 1. Ph3P=CHPh PhH2C=HC 1. excess EtOH . aldehyde proton and carbonyl carbon. excess NaBH4 OH HO Ph HO Ph (d) (e) OH O (f) O 1. –78°C HO2C CO2Et CO2Et CN (c) 3. excess SOCl2 5. H2O2 HO2C 4. CH2=CHCN OHC 2. H O IR: alkene signal at 1645 cm–1 O IR: alkene signal at 1645 cm1 and the aldehyde signals at 1725 cm–1 and 2815 cm–1 6 4 PPM 2 0 10 5 PPM 0 150 100 PPM 50 0 200 carbons and protons for two C=C 100 PPM 0 47. heat 4. and only one C=C unit . LDA . Do not attempt these problems until chapter 14 is read and understood. Me3SiCl 3. excess PhMgBr 3. –78°C 3. –78°C 2. O3 . THF . O3 . diethyl fumerate 2. H3O+ 5. methyl acrylate 2. O3 . MeCO3H O NMe2 O Spectroscopic problems. Me2S OHC 1. Me2NH 7. Me2S 5.
O O 5-norbornene-2. 6 4 PPM 2 0 6 4 PPM 2 0 bicyclo[2.48. and it will be the major product of this equilibrium reaction.3-dicarboxylic anhydride 3-(vinyloxy)prop-1-ene 52.2. One has six C=C protons whereas the other has only four.2.1]hept-2-ene 50. The main difference is the two methyl groups on C=C versus two methyl groups on sp3 carbon. O O 51. The diene on the right is more stable. . CN cyclohex-3-enecarbonitrile 53.5-diene 49. O 7-oxabicyclo[2.1]hepta-2.
Chapter 25 29. acceptor 31. the hydrolysis step for hydride reduction. d (a) O CO2Et O d O a (b) OH O O O (c) OH O a O O O H (d) d H a acceptor O (b) donor Br (a) Br (d) O (c) acceptor (e) donor (f) MgBr O acceptor 30. but it is part of the synthesis and understood to be there. or enolate anion reactions is omitted. In all cases. Grignard reactions. .
NaOEt . PBr3 O PCC OH OH 1. excess KOH . EtOH . Pd-BaSO4 quinoline Br 1. LDA . THF . 200°C (e) OH OH aq. BuMgBr 2. H2O 2. PPh3 2. CH3CHO 3. LiAlH4 (c) O Br 1. Hg(OAc)2 . NaOH. THF . BH3 . NaN3 5. PCC (b) NH2 1. Mg 2. CCl4 2. NaBH4 1. H+ 4. NaBH4 3. –78°C\ 2. LDA . reflux 5. H2O2 3. H2O 2. H2O2 3. –78°C 2. EtOH . MeI 3. NaBH4 OH (f) H2 .H (a) O 1. Br2 . –78°C\ 2. ether 2. OsO4 t-BuOOH 1. PBr3 4. H3O+ 6. NaBH4 O 1. PCC (d) OH 1. MeI 3. O3 . EtOH . CH3CH2CHO 1. ehat . Hg(OAc)2. BuLi 3.
32. In all cases, the hydrolysis step for hydride reduction, Grignard reactions, or enolate anion reactions is omitted, but it is part of the synthesis and understood to be there. OH O OH (a)
Me2CHMgBr OH (b) Ph Ph O
1. PCC 2. CH3CH2CH2CHO 3. PCC O
1. PhMgBr 2. PBr3 3. KOH , EtOH 4. MeCO3H
1. Hg(OAc)2 , H2O 3. PCC 2. NaBH4
O 1. LiAlH4 2. PCC 3. Ph3P=CEt2
1. aq. OsO4 , t-BuOOH 2. acetone , H+
CN N Ph Ph 1. LDA , THF , –78°C 2. MeI 4. PhCH2Br 3. LiAlH4 Ph O Br 1. Ph3P=CHCH3 3. H2O2 , NaOH 2. BH3 , ether 4. PBr3
CO2H 1. O3 , –78°C 2. Me2S 3. (CH2CH2CO2Et/LDA) (enolate addition) 4. H3O+ (elimination and hydrolsyis of ester) 5. H2 , Pd
1. PCC 2. Gringard of 2-bromobutane (a) OH 3. PCC O (b) CN 1. Gringard of 2-bromobutane 2. H3O+ 1. BH3 , ether 2. NaOH , H2O2 3. PCC 4. Gringard of 2-bromobutane 5. PCC 1. Me3CO3H 2. MeMgBr 3. PBr3 4. KOH , EtOH 5. BH3 , ether 6. H2O2 , NaOH 7. PCC 1. PCC 2. LDA , THF , –78°C OH 3. EtI 4. separate isomeric products from alkylation of the other side of the carbonyl 1. CH3CH2CHO 2. PCC O O O
CHO (a) 1. LDA , THF , –78°C 2. 1-bromobutane CHO O Ph3P=CHCH3 MeCO3H
MeMgBr (b) CHO
OH 1. PBr3 2. MeC C:–Na+ O MeCO3H
H2 , Pd-C
1. LDA , THF , –78°C 2. CH3CH2Br 3. NaBH4 4. PBr3
1. CrO3 , aq. H2SO4 , heat 2. EtOH , H+ 3. LDA, THF , –78°C 4. MeI 5. H3O+ CO2H
1. LDA , THF , –78°C 2. BuI 3. H3O+ 1. NaCN , DMF 2. H3O+ , heat 1. O3 , –78°C 2. H2O2 3. EtOH , H3O+ 4. LDA, THF , –78°C 5. MeI 6. H3O+ CO2H CO2H CO2H
O NEt2 Ph
O OEt Et2NH , heat O OEt Ph 1. LDA , THF , –78°C 2. PhCH2Br O OEt 1. LDA , THF , –78°C 2. BuI
37. Cyclohexanol is converted to bromocyclohexane with PBr3 and then to cyclohexene with KOH in ethanol. Ozonolysis of the alkene, with hydrogen peroxide as the second step gives the dicarboxylic acid. Esterification with ethanol and acid gives the diester, and treatment with sodium ethoxide gives the ethyl ester of cyclopentanone 2-carboxylic acid via Dieckmann condensation. Hydrolysis to the acid and heating to 250°C leads to decarboxylation and formation of cyclopentanone. Br OH CO2H 1. O3 KOH PBr3 EtOH 2. H2O2
CO2H EtOH H+ CO2Et NaOEt EtOH reflux CO2Et CO2Et O CO2H H3O+ O 250°C O
H2 , Pd
HgSO4 aq. Hg(OAc)2 O
NaBH4 OH O OH
1. BH3 2. H2O2 , NaOH
CrO3 , aq. H2SO4
Sn , HCl H3O+ , heat CN
1. MeMgBr 2, H3O+ , heat
1. MeMgBr 2. H3O+ heat O 1. O3 , –78°C 2. Me2S
H2 , Pd Ph3P=CHCH3 CH3CHO
1. PBr3 2. KOH , EtOH OH
O LiAlH4 OH
CHO also reduction of ketones
CO2Et also reduction of acids or acid chlorides
1. BH3 , ether 2. H2O2 , NaOH
43. In all cases, the hydrolysis step for hydride reduction, Grignard reactions, or enolate anion reactions is omitted, but it is part of the synthesis and understood to be there.
H (a) O 1. EtMgI 2. PCC O H O 1. LDA , THF , –78°C 2. EtI
(b) H , Pd-BaSO4 quinoline O (c) EtO2C HO2C Ph 1.NaOEt , EtOH 2. PhCH2Br O 1. MeMgBr 2. PBr3 3. KOH , EtOH (d) CO2H 1. PBr3 2. enoalte anion of CH3CO2Me 3. H3O+ Ph
1. NaNH2 O 2. PhCH2Br
1. NaNH2 2. EtI O
1. NaNH2 2. Me2CHBr
1. O3 , –78°C 2. H2O2 3. EtOH , H+
1. NaNH2 2. PhCH2Br 3. Na , NH3 , EtOH OEt (f) 1. NaBH4 2. NaH 3. EtI
1. LDA, THF , 78°C 2. MeI
1. LDA , THF , 78°C 2. CH3CH2CH2Br
PhCH2Br OCH3 OCH2Ph 1.Ph (g) OH O 1. AgO 5. THF . and are cleaved. 45. Methyl ethers are very robust. PhMgBr 2. CH3CH2CHO 4. EtOH MeI 2. Mg . ether 3. NaBH4 2. NaOEt EtOH O 2. The fact that the methyl ether is so robust limits its use as a protecting group to those molecules where treatment with strong acids will not cause problems elsewhere. CH3CH2Br O HO (h) Ph O O PhMgBr OH (i) 1. 150°C OCH2Ph OH . Methyl ethers also react. with Lewis acids such as BBr3. NaBH4 (Me2CH)2CuLi O OH 1. H2O 1. but those are rather harsh reagents that may also react with any other functional group that is present. MeCHO O O OH 1. they are quite stable and do react with very many reagents. 78°C 2. OH OH (a) O OCH3 1. PCC 44. NaH 2. that is. PBr3 2. PBr3 3. Methyl ethers react with HI and HBr. NMe3 4. NaOEt . LDA .
O OCH2Ph CH3CO3H O 1. EtMgBr CHO 2. H3O+ O O OH . BH3 . LDA . MeI O OMe OCH3 O O H O (b) O O O O Cl AlCl3 O O 1. H2 . THF . NaBH4 2. ether 2. Pd OH OCH2Ph OH OH THF -78°C OCH2Ph O 1. –78°C 2. NaH 2. H2O2 . NaOH O O PCC O O 1. Br OH HOCH2CH2OH H+ O O 1.
H3O+ OH PCC O 1. THF . A convergent synthesis is provided for each question. -78°C 2. LDA . THF .PCC O O O O H3O+ O 46. BrCH2CN . PhCH2Br O Cl CuLi 2 O CHO Ph3P=CHCH=CH2 Diels-Alder O CO2Et H CN (b) O CO2Et O CN 1. –78°C 2. MeMgBr CHO 2. (a) O O CHO 1. LDA .
ether 2. H3O+ OH CN 1. H2O2 OH O 1. –78°C H 2. SOCl2 3. Ph3P=CMeCN 2. EtOH O Cl BF3 Ph O 1. O CN CO2Et CN CO2Et 3. Pd (removes benzyl ether protecting group and reduces the C=C) OH CN PCC O CN Ph O CN O 1. aq. PBr3 2. LDA . NaOH . NaBH4 2. BH3 . THF .O CN 1. NH4Cl 1. NaH 2. PCC O . PhCH2Br O 1. Me2CuLi CO2Et CN 2. H3O+ H excess H2 .
5-diethyl-2-isopropyl-2H-pyran 43.4.5-dimethyl-1Himidazole Et (h) 2-propylpyrimidin-5-ol 42.6-diamine furan-3-amine OH (g) O2N NH 3.4-dinitro-1H-pyrrole NH2 (i) N N 6-nitropyrazin-2-amine NO2 O2N (f) H3CH2CH2C Me 1-ethyl-4. The major product is shown for each reaction.4-dichloropyrazole Cl (d) Cl N Me N (b) HN N.4-diacetylpyrrole N (e) (f) N NH2 O2N (g) N N N 1-methyl-4-chloroimidazole Br (h) N Br (i) N N NH2 N 5-aminopyrimidine 2. O CHMe2 3. .3-dimethylpyrrole O 3.pyridine-2.5-dibromopyridazine 3-nitropyrazine 2-amino-5-methylpyrimidine (a) O (b) Br S Cl (c) O (d) H2N N NH2 O 1-(furan-2-yl)propan-1-one N (e) Me N-Et Me H2N 3-bromo-2-methylthiophene N N 5-chloro-4-isopropyl.Chapter 26 41. O Me (a) Me Cl (c) N N 2.6-trimethylpyridine N 3.
.NO2 (a) N CH3 N H N (b) N CH3 (c) N N CH3 O2N N N CH3 H N N CH3 CH3 CH3 Cl CH3 (d) O O OH O2N (e) O (f) O O2N SO3H O NH2 O HO (g) O O (h) O HN (i) N Ph N N O NO2 SO2H Ph (a) N N H N (b) N O (c) N NMe2 44.
1'-(3. Molecule B should react faster. 3-bromopyrrole should be more reactive.3-dioxolane 2.6-tetramethyl-1. In both cases.3-dimethyl-4-nitropiperazine pyrimidin-5-amine .2. nucleophilic substitution at C3 will generate a negative charge in the ring that will be delocalized on either oxygen (bromofuran) or nitrogen (bromopyrrole). but better than A. which is very destabilizing.45.3-dithiolane S (j) H N H H H 2-tert-butyl-1-propylimidazolidine H 2-isopropylhexahydro3.4-trimethylimidazolidine Br (e) N Br O N Ac (f) Cl (g) Br Br (b) O Me O Et (c) N NO2 C4H9 N (d) S S Et 2. but two where it is delocalized on carbon. so the intermediate for B is more stable . Reaction with B generate one resonance contributor with the positive charge on nitrogen. Based on this analysis. so an intermediate with negative charge should lead to greater instability for the oxygen-containing furan ring when compared to the nitrogen-containing pyrrole ring. Reaction with A generates an arenium type ion in which the positive charge will be delocalized on all three nitrogen atoms.2-diethyl-1. N A N N *N * N N * Br H B N H N Br N * N N * N * 46.5-dichloro-1.3-dioxolane NO2 N (k) N N (l) N N H2N (i) S 2-ethyl-4-isopropyl-5methyl-1. 47.3.4-dithiane H 1-butyl-3-nitropiperazine O O (h) O O Ac 1.4-dioxane 2. The charge density is larger on oxygen than on nitrogen.2diyl)diethanone Cl O 2.2-diethyl-1.3-dioxane 4. Me N (a) N Me 1.5-dibromo-1.not great.4dibromopyrazolidine-1.6.
2-diethylazetidine 3-chlorothiane 2-phenylthiirane S (l) NO2 (g) N (h) N-propylaziridine 2.4-tetrahydropyridine 1. (a) NH O (b) 2.48.6-dibromoquinoline Br N (d) NO2 3-butyl-5-nitroisoquinoline 8-chloroquinoline 1-methyl-7-cyanoindole (e) O2N N (c) H N Me 6-methyl-7-nitroisoquinoline Cl N (f) 6-ethylindole CN Me N .2.5-tetramethylpiperazine O2N (e) N NH 1-ethyl-4-nitropyrazolidine O2N (f) N H cis-3.2-dihydropyrimidine 1.4.2-dihydropyridine 50. O (a) Me N N Me (b) N N Me O Br (c) Br (d) O trans-2. N (a) (b) Br 4.5-dinitropiperidine Cl (k) N.3.2.3-dihydrofuran (c) NH NH (d) N 1.4-dioxane O O Me Me 3.3-diphenyloxetane 49.3-dimethyl1.5-dibromotetrahydrofuran N-acetyl-3-ethylimidazoline 1.3-diethyloxirane (i) N (j) S O cis-2.
as well as the final product. AlCl3 N Br OMe Br + N N Br O (c) N acetyl chloride AlCl3 O N N + + N OMe NO2 (d) N HNO3 H2SO4 Me (e) N H Br2 . AlCl3 Br N H NO2 (f) N H HNO3 H2SO4 N H N + NO2 Me N 52. All intermediate products are shown. . The major product or products are shown. Br (a) N OMe (b) N Br2 . AlCl3 Br2 .51.
NaCN . Pd° . heat Ph N Ph Ph NH N Ph O NH2NH2 . THF 2. heat N EtO2C Et Et N H CO2Et Ph Br 3. H2 . 1-aminobutane . POCl3 4. O3 . CO2Et (f) 1. heat 2. polyphosphoric acid NH O (g) Ph O (h) C3H7 O Ph O H2SO4 EtNH2 . AcOH . Pd-C 2. phenyl acetyl chloride Ph (c) Ph CN 3. heat Ph 1. Me2S (d) Et O (e) 2 eq.4-dimethylheptanal 4.O (a) Ph O (b) Ph O Ph O Ph NH4OAc . H2 . Ni(R) NaNO2 . heat N Ph Et 1. heat NH2 O Ph O NHEt C3H7 HN Ph C3H7 C3H7 . 4.
Pyrrole is the more reactive ring in this system. O3 . heat O 1.OH (i) Ph O Ph Ph O heat Ph H2NCHO . -78°C 2. H2SO4 (k) CH2Ph (l) CH2Ph O (m) 1. and will be the lower energy intermediate that leads to the major product. Me2S 2. PDC . The charge is placed on C2. Me2S 2. which means that an oxocarbenium ion resonance contributor will be formed. THF .P4S10 . heat Ph Ph Ph N N H Ph N N H (j) NHNH2 1. Electrophilic substitution at C3 generates an intermediate such as the one shown. heat Ph S Ph Ph NH N Ph NH N 53. and will react with Br+. NH2NH2 . HN HN O Br+ O Br 54. O3 . . whereas attack at C2 generates more resonance contributors. No other resonance contributors are possible. 4-phenylbutanal 3. CH2Cl2 4. LDA . cat. has greater stability.
the products are 3-amino pyridine. 60. along with 2-amino pyridine and 4-amino pyridine. It is a four. which is known as 2-pyridone. N HO O 58. and this equilibrium is a form of tautomerism known as hydroxypyridine-pyridone tautomerism N OH N H O Spectroscopic problems. Do not attempt these problems until chapter 14 is read and understood. confined to a four-membered ring. There is a difference in the aromatic proton region. The pyridine ring is deactivated and simply reacts too slowly with an oxocarbenium ion to give the Friedel-Crafts reaction. The product is 2-hydroxypyridine. The presence of the nitrogen pushes the ortho proton further downfield relative to toluene.H X+ O O X O H X S N H 55. 59. Remember that amides can exist in the imine form (amide I and amide II bands in the infrared). All of the following problems involve heterocycles. 3-Bromopyridine reacts with sodium amide. which also exists in the lactam form shown. which does not follow the Hückel rule. and very unstable. analogous to cyclobutadiene. N 57. It is anti-aromatic. A Friedel-Crafts reaction would require reaction at a pyridine ring.-electron system. 56. which does not undergo electrophilic aromatic substitution reactions such as this very well. and there are fewer identical signals. . This reaction proceeds via a benzyne intermediate.
CH3 N CH3 8 6 4 PPM 2 0 8 6 4 PPM 2 0 61. although there will be some differences in coupling constants (not observable in the spectra shown). Likewise. CH3 N CH3 N 8 6 4 PPM 2 0 8 6 4 PPM 2 0 150 100 PPM 50 0 150 100 PPM 50 0 62. . There are few differences in the proton NMR for 2-methylquinoline from 4-methylquinoline. In the C13 spectra. Therefore. not that the methyl group of 2-methylquinoline is a bit further downfield due to its proximity to the nitrogen. the aromatic protons in the proton NMR are further downfield in furan. because it is more electronegative. the aromatic carbon atoms are further downfield in furan when compared to those carbon atoms in pyrrole. and more electron withdrawing. Oxygen is more effective at deshielding relative to nitrogen.
3-Nitropyrrole 67.O N H 8 6 4 PPM 2 0 6 4 PPM 2 0 150 100 PPM 50 0 100 PPM 50 0 63. three different protons and they clearly show in the proton NMR.5-Dimethylpyridine 65. and there is only one peak. 2-Ethylfuran 66. Pyrazine is symmetrical. 2-(4-Pyridyl)butane . N N pyrazine N Pyrimidine has N pyrimidine 8 6 4 PPM 2 0 10 5 PPM 0 64. 2. as all protons are identical.
3-diphenylpentan-1-amine H NH2 N H (f) (g) N Me (h) N NEt2 (d) N 3-methyl-1-propylpyrrolidine Ph 3-phenylazetidine Me (e) Me (2R.3.2.3. THF 3.3R)-2. NaN3 . CH2Cl2 2.7.8hexahydroazocine triethylamine 47. hydrolysis CH2NH2 NHCH2Ph OH (b) Br (S) NH2 (R) (c) (d) 1.Chapter 27 46. H+ 3. The major product or products are shown. PCC . THF 4.N-diethyl-1.N-diethylhexan-3-amine Ph Et (i) N Et (j) N (k) 1. H (a) N N-ethylpropan-1-amine (b) H N (c) Ph Ph N. (a) 1. KCN . PhCH2NH2 . No mechanisms are provided. Pd-C NH2 . THF OH 3.3-dimethylpiperidine 2-methylhexan-3-amine N. HNO3 . PBr3 2.6-trimethyldecan-4-amine N N. cat. Pd-C 1. H2 . THF 2. LiAlH4 . H2 . LiAlH4 . hydrolysis 1. H2SO4 2.4.2-diethylaziridine (Z)-1-benzyl-1.
If the phenyl groups withdraw electron density from the N-H bond. The conjugate acid of triethylamine is Et3NH+ and the conjugate acid of ethylamine is EtNH3+. hydrolysis CH2NH2 48. NEt3 Br 49. 50. 2-pentanone. -78°C 2. HCl NHEt MeI NMe2 (g) CO2H 1. 2-butanone 3. THF 3. Triethylamine is a base. making it more polarized and more acidic. cat. a primary amine is a stronger base in solution relative to a tertiary amine. 200°C (c) CHO EtNH2 . LiAlH4 . Zn° . BuLi . which are electron releasing. benzaldehyde N 4. THF . H2O 3. Phenyl groups are electron withdrawing relative to the propyl groups. 51. triethylamine. H+ (a) N H N Br (b) 1. H+ CH=NEt O OH Ph (d) 1. 200°C 2. In general. Me3N 2. NH3 . cat. Give the major product for each of the following reactions. Ag2O .(e) O NHMe (f) EtNH2 . hydrolysis H . If ethylamine is the stronger base. then the conjugate acid will be a weaker acid when compared to the conjugate acid of the weaker base. and in the presence of a secondary amine and a protic solvent an E2 reaction can occur to give the alkene.
and the least substituted alkene possible from such a salt is ethylene.O (e) 1. H HO– N 53. NH4Cl 3. NaBH4 . EtOH 2. NH2 O OH NH2 O OH 4-aminohex-5-enoic acid O OH N aziridine-2-carboxylic acid H 3. pyridine O 3-phenylbutanoic acid Ph (f) N H H O N H 25°C Et3NH+ Br- (g) O. PCl3 . aq.Na+ OH + Et3N 52.4S-dihydroxyhexanoic acid . A triethylammonium salt has -hydrogen atoms on the ethyl groups.4-diphenyl-5-aminohexanoic acid O H2N OH Me N-methylpiperidine-4-carboxylic acid N 3-aminobenzoic acid O OH OH NH2 OH O OH 2R-amino-3R.
O O HO NH O OH N-ethyl-3-amino-1. (a) Compound A should have the lowest pKa due to the electron withdrawing effects of the OMe group. The Nphenyl group is electron withdrawing. Ph C N H Me N H D CO2H CO2H 55.5pentanedioic acid O NH OH NH2 2S-amino-3-phenylpropanoic acid pyrrolidine-2Scarboxylic acid OH HN O OH Me N. NH3 NH3 CO2 NH3 (R) NH3 (R) NH3 (R) NH3 (R) (R) NH3 CO2 (R) CO2 H3C CO2 CO2 CO2 NH3 Me (R) HO (R) NH3 NH3 CO2 (R) SMe CO2 (R) NH3 CO2 CO2 OH CO2 OH SH NH2 (R) NH3 CO2 H2N O NH3 (R) OH (R) NH3 CO2 HO O NH3 (R) O CO2 O CO2 . which will make the N-phenylammonium salt more acidic.3-dimethyl-2Saminobutanoic acid 54. NH2 A MeO CO2H CO2H NH2 B (b) The second pK2 value is for loss of a proton from the ammonium salt of the amino acid. The more acidic compounds will have the larger pK2. so the answer is C.
H2 . The electron withdrawing inductive effects of the phenyl group lead to a more acidic compound. but it also converts the alkaline group to an ammoniums salt. Acidification in an aqueous medium to pH 4 leads to hydrolysis of the ester to the acid. which is water soluble. Na phthalimide 2. H3O+ BrCHCO2Et NH3 . The phenyl group is electron withdrawing whereas the alkyl group in isoleucine is electron releasing. the ammonium salt will not likely be soluble in dichloromethane. heat H2NCH2CO2H H2NCH2CO2H 58. pH 4 Ph O OH 1.H2N NH3 (R) N NH3 N H (R) NH3 (R) H2N N NH NH3 (R) N H CO2 CO2 CO2 NH2 (R) H CO2 CO2 56. 1. Br NH2 O PBr3 . 57. Therefore. NaOH 2. Pd 3. NaN3 2. aq. hydrazine H2NCH2CO2H . so both pK values are smaller. Br2 NH3 O Ph O Ph Ph O O O NH3+ 1.
THF OH 3. PBr3 2. 60.O (a) NH2 O 1. NaCN 4. Br2 4. PBr3 . NH3 O H2N CH C CH3 OH OH (c) CH3CO2H . O 1. Br3 2. H2 . Pd H2N CH C CH2 OH (a) Ph O (b) CO2H 1. PBr3 . H+ OH NH2 2. PBr2 3. propanoyl chloride HN excess BuOH OH H+ O OBu NH2 O OH OEt 59. NaCN 2. LDA . EtOH . H3O+ 5. Br2 6. NaN3 5. neutral pH (b) NH2 O (c) 1. NH3 H2N CH C CH CH3 CH3 1. LiAlH4 2. Ac2O NHAc O O OH 2.
heat 2. DMF . CrO3 . H3O+ CO2 (CH2)12 NH3 . CO2 NH3 O O N O O N Ph pyridine O N Ph O O H3O+ Ph pyridine Me2CHO N O 1.(d) HO2C 1. NaH H2N 3. aq. 200°C 6. NH3 O CH C CH CH3 CH2 CH3 OH 61. Br2 7. PBr3 . (a) HOCH2(CH2)10CH2Br 1. Ph Cl 2. 2-bromobutane CO2H 4. H3O+ 5. aq. H2SO4 4.H+ CO2H NH O O O H3O+ Ph O Ac2O NaOAc N O Ph O O NH3 O O NH3 Ph O O N Ph Ph pyridine PhCH2CHO O O N H3O+ Ph Ph O O NH3 62. H+ 2. EtOH . NaCN .
LDA . EtOH . Pd 5.C O2H (b) CN 1. H3O+ 2. NH3 . PhCH2Br 8. -78°C 2. H3O+ 2. O O H2N CH C H O CbzHN CH C H H N OH Cl O O Ph O CbzHN CH C H 1. H3O+ 9. EtOH 6. LDA . NaCN 7. H2 . H2O2 3. –78°C 3. PBr3 NH3 NH3 CO2 Ph NH3 (d) 5. H3O+ Ph CO2 (c) 1. Pd-C 10. H3O+ 1. Pd-C O H2N CH C H H N O H CH C N CH3 O CH C CH CH3 CH3 OH . –78°C 7. O3 . H+ 2. –78°C 2. H3O+ 6. H2O2 3. H2 . THF . H2N O CH C OEt CbzHN OH H2N CH C CH3 DCC O OEt NEt3 O CH C OEt CH3 O H N H CH C N CH3 O CH C CH CH3 CH3 OEt CH C H CH CH3 . DCC CH3 1. THF . H2 . ethylene glycol . Pd CO2 63. H+ 4. H2 . NaBH4 4. SOCl2 5. 1-bromo-2-phenylbutane 4. O3 .
so the amine unit is not NH2. 66. CO2H R O (a) O O O SH (b) O (c) O O R CH2OH H O O HO N RCHO + CO2 + 4 H2O NH2 + glycine R=H H O H O N O O HO O O + methionine R = CH2CH2SH O H O O N O HO + serine OH O O . which makes the electrons less available for donation. At neutral pH. 67.64. but rather NH3+. The electron pair on nitrogen is partly delocalized onto the adjacent carbonyl. In other words. an amino acid exists as a zwitterion. 65. In phe-ala.. it is less basic. the PhCH2 group and the methyl group are probably anti in the best conformation.
O O + valine (d) O (e) O O O (f) O O O + arginine + histidine R = CH2-imidazole N N H H2N NH O N O N HO O R = Me2CH H O O HO N O H O O O O HO R= CH2C(=NH)NH2 H O O 68. O H2N (a) H CH C N H O CH C CH3 H N O CH C CH2 CH2 S NO2 O O2N H N CH C CH3 CH3 H N O H N H N O CH C CH2 C NH2 O CH C CH2 C NH2 O H N O H N O CH C CH CH3 CH2 CH3 O CH C CH CH3 CH2 CH3 OH H2N O CH C H OH OH 1. O2N 2. 6N HCl NO2 F CH C CH2 CH2 S CH3 .
O H2N (b) CH C CH2 CH2 C NH2 O H N O CH C CH2 CH2 C NH2 NO2 O O H N O CH C CH CH3 CH3 H N O CH C CH2 OH OH 1. O2N 2. 6N HCl F CH2 N H O O CH C CH C OH O H2N CH C CH2 N H N NH OH HN CH2 CH2 HN . O2N 2. 6N HCl NO2 F O H N CH C CH CH3 CH3 H N O CH C CH2 OH OH H2N CH2 CH2 C NH2 O C OH O CH C OH O2N H N CH C CH2 CH2 C NH2 O O O O H2N (c) CH C CH2 N NH HN NO2 O O2N HN CH C CH2 N H H N O CH C CH2 N H CH C HN CH NO2 CH2 1.
NMe2 O H2N (a) CH C CH2 CH2 CH2 NH C NH2 NH OH H N O CH C CH2 H N O CH C CH OH CH3 H N O CH C H NMe2 OH 1. SO2Cl NMe2 2. SO2Cl 2. 6 NHCl NMe2 + glu + ser + thr O HO HO2C N H SO2 . 6 NHCl O HO H N NH2 SO2 N H + tyr + thr + gln HN O H2N CH C CH2 (b) CH2 C OH O H N O CH C CH2 CH2 C OH O H N O CH C CH2 OH H N O CH C CH OH CH3 OH 1.69.
N C S . O H2N (a) CH C CH2 CH2 CH2 NH C NH2 H2N NH OH O CH C CH2 H N O CH C CH OH CH3 H2N OH H N O CH C H NH OH S O NH H N O CH C CH2 H N O CH C CH OH CH3 2. SO2Cl 2. CF3CO2H H N O CH C H OH 1. 6 NHCl 70.NMe2 O H2N (c) CH C CH2 H N O CH C CH CH3 CH2 CH3 H N O CH C CH2 CH2 CH2 CH2 NH2 HO Ph N H O SO2 + ile + lys NMe2 OH 1.
CF3CO2H OH 1. N C S HN CH C CH CH3 CH2 CH3 71.O H2N CH C CH2 (b) CH2 C OH O H N O CH C CH2 CH2 C OH H2N O H N O CH C CH2 OH H N O CH C CH OH CH3 2. N C S O CH C CH2 CH2 C OH O H N O CH C CH2 OH H N O CH C CH OH CH3 HO2C OH O NH S O H2N (c) CH C CH2 H N O CH C CH CH3 CH2 CH3 H N O CH C CH2 CH2 CH2 H2C O NH2 O H N CH C CH2 CH2 CH2 H2C NH2 Ph OH O NH S 2. CF3CO2H OH 1. .
O H2N (a) CH C CH2 CH2 CH2 NH C NH2 NH OH H N O CH C CH2 H N O CH C CH OH CH3 H N O CH C H OH NH2NH2 100°C O H2N CH C CH OH NHNH2 O H2N CH C CH2 NHNH2 CH3 H2N NHNH2 O CH C H OH O H2N CH C CH2 CH2 CH2 NH C NH2 OH NH O H2N CH C CH2 (b) CH2 C OH O H N O CH C CH2 CH2 C OH H2N O H N O CH C CH2 OH H N O CH C CH OH CH3 O O NHNH2 H2N CH C CH OH CH3 OH H2N NHNH2 H2N CH C CH2 O OH NHNH2 OH NH2NH2 100°C O CH C CH2 CH2 C OH O CH C CH2 CH2 C OH O .
H3O+ H2N CH C CH2 OH NH2 H2N CH CH2OH CH CH3 CH2 CH3 O CH C CH3 OH H2N CH CH2OH CH CH3 CH3 H2N CH CH2OH CH2 CH CH3 CH3 . LiAlH4 2.O H2N (c) CH C CH2 H N O CH C CH CH3 CH2 CH3 H N O CH C CH2 CH2 CH2 CH2 NH2 O H2N O CH C CH CH3 NHNH2 CH2 CH3 H2N NHNH2 OH NH2NH2 100°C O CH C CH2 CH2 CH2 CH2 NH2 OH H2N CH C CH2 72. LiAlH4 2. H3O+ H2N OH O 1. H3O+ H2N CH C CH2 SH OH OH 1. LiAlH4 2. O H2N (a) CH C CH2 OH H N O CH C CH CH3 CH2 CH3 O (b) H2N CH C CH3 O H2N (c) CH C CH2 SH H N H N O CH C CH CH3 CH3 O CH C CH2 CH CH3 CH3 OH O 1.
75. (a) ala-ala-thr-cys-asn-val-phe-leu-thr-his-arg-pro-phe trypsin pro-phe ala-ala-thr-cys-asn-val-leu-leu-thr-his-arg chymotrypsin ala-ala-thr-cys-asn-val-phe-leu-thr-his-arg-pro-phe ala-ala-thr-cys-asn-val-phe trypsin leu-thr-his-arg-pro-phe (b) tyr-ile-ile-ile-arg-gln-asp-val-his-his-phe-ile-tyr tyr-ile-ile-ile-arg tyr-ile-ile-ile-gly-gln-asp-val-his-his-phe-ile-tyr tyr gln-asp-val-his-his-phe-ile-tyr chymotrypsin tyr-ile-ile-ile-gly-gln-asp-val-his-his-phe ile-tyr O H2N (S) O O N H (S) OH O H2N (S) (S) OH anti N H syn 74. O H2N CH C CH3 H N O CH C CH2 CH2 C NH2 O H N O CH C CH2 H N O CH C CH2 OH OH .73.
assume the N terminus is on the left (gly) and C terminus is on the right (arg). (a) gly-lys-ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg-glu-tyr-ile-lys-arg gly-lys ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg trypsin arg glu-tyr-ile-lys .O H2N (S) O N H (S) OH H N O (S) N H (S) CO2H H2N (S) CH3 O N H (S) O H N O (R) OH N H (S) CO2H CH3 76. For gly-lys-ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg-glu-tyr-ile-lys-arg. 4R-amino-3S-hydroxy-5S-methylheptanoic acid OH (S) (R) (S) Aplidine O O (S) (S) L-alanine O O Me O NH (S) O O (S) HN (S) L-proline N O O (S) N O (R) N H (S) O O L-leucine N D-leucine N Me (S) S-proline 4-amino-3S-methylbutanoic acid L-4-methoxy tyrosine OMe 77.
The activation energy to attain the pentacoordinate SN2 transition state is too high for this reaction to occur. 79. 2. The ethyl ester of 2-bromo-2-methylbutanoic acid is a tertiary halide. H2 catalyst 80. O EtO O SN2 is not possible N:– O Br Ph O H NH2 CO2Et Ph HN CO2H Ph N H CO2Et 1. and the reaction with phthalimide anion is a SN2 reaction. H3O+ .(b) gly-lys-ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg-glu-tyr-ile-lys-arg gly-lys-ser-phe (c) phe ala-ile-ile-trp chymotrypsin ile-lys-arg leu-asp-met-pro-arg-glu-tyr gly-lys-ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg-glu-tyr-ile-lys-arg gly-lys ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg carboxypeptidase B arg glu-tyr-ile-lys Staphylococcal protease (d) gly-lys-ser-phe-phe-ala-ile-ile-trp-leu-asp-met-pro-arg-glu-tyr-ile-lys-arg gly-lys-ser-phe-phe-ala-ile-ile-trp-leu-asp met-pro-arg-glu tyr-ile-lys-arg O MeO N H O CH C CH2 H N O CH C CH2 OH H N O CH C CH CH3 CH2 CH3 OEt 78.
CO2 NH3 O O N Ph pyridine H O O 1.81.H+ CO2H Ac2O NaOAc NH Ph O O O N O O N H3O+ Ph Ph O O NH3 O pyridine O H O O N Ph H3O+ Ph O O NH3 N Ph Ph O . Ph 2. Cl aq. O H2N NH2 O Ph Ph O H2N NH2 S O N N NH HN NH NH OH HO S H2N NH2 O NH S O 82.
These problems involve amines.O O N Ph O O pyridine H O O H3O+ O Ph N Ph Ph NH3 Ph Ph Ph Ph Spectroscopic problems. which will have the broad signal at 3300 cm–1 for the OH plus the sharp signal at 2240 cm–1 for the nitrile. and the amino protons will be buried in this signal. a doublet methyl in the proton NMR and a triplet methylene downfield at about 3. 83. The amino acid has the acid peak at about 12 ppm in the proton NMR. but a doublet methyl + a triplet methyl 4 2 PPM 0 4 PPM 2 0 40 PPM 20 0 40 PPM 20 0 note C-N downfield carbon missing in the other 84. 4-aminobutanoic acid will have the broad peak associated with the COOH unit at 2500-3000 cm–1. there will be the carbonyl at 1725 cm–1. amino acids. Do not attempt these problems until chapter 14 is read and understood.3 6 2-aminopentane No N-methyl. The cyano-alcohol has the nitrile carbon at about 130 ppm. and derivatives of amino acids. This sharply contrasts with 4-cyano-1-butanol. The NMR data for the two compounds are very different. . and a carbonyl carbon at about 180 ppm in the carbon NMR (assuming the amino acid and not the zwitterion). H N IR: The secondary amine will have pne peak at about 3300 cm–1. In the infrared.8 ppm. NH2 Me N-methyl-1-amino butane triplet methyl + N-methyl at 3. In addition. due to the CH2-O unit. whereas the primary amine will have two.
there are differences in the methine-methylene pattern in A and the methylene-methine pattern in B. where A has the methine carbon further downfield. Must decarboxylate first O O HO O OH EtO O O OEt EtO O OEt .CO2H NH2 CN CO2H CN OH 10 PPM 5 0 4 2 PPM 0 150 100 PPM 50 0 100 PPM 50 0 85. which cannot react with phthalimide via substitution. Therefore. the question asks for differences between A and B. O O EtO OEt Br cannot do a substitution here. The most obvious difference is the number of carbon atoms in A . Bromination of the malonate will give a tertiary bromide.one more than B. Decarboxylation must occur at the malonic acid stage. Likewise. There are also differences in the sp3 carbon atoms in A and B. before the reaction with phthalimide.
O HO A O OH B O OH O OEt O Br OEt O N:– O O N:– O O H2N OEt O OH A B 10 PPM 5 0 10 PPM 5 0 150 100 PPM 50 0 150 100 PPM 50 0 86. Pd-C NH2 NH2 CO2H MINOR no methyl groups 10 5 0 CO2H doublet methyl PPM 10 PPM 5 0 . HBr 2. NaN3 3. CO2H 1. H2 .
but there are three carbonyl peaks.methyl + 3 methylene C all methylene C 150 100 PPM 50 0 150 100 PPM 50 0 87. It is a bit difficult to see in the 13C spectrum on the bottom left. Phenylalanine methyl ester. and only two in the spectrum on the bottom right. 92. 91. 90. 4-Aminohex-5-enoic acid Ethyl L-leucinate Dimethyl 2-bromomalonate Ethyl gly-val (N-acetyl) . There are other subtle differences as well. O O O O IR is not much H H AcHN CH C N CH C OEt help as these EtHN CH C N CH C NMe2 spectra are similar CH3 H CH3 H N-acetyl ethyl ester of ala-gly N-ethyl-dimethyl amide of ala-gly 8 6 4 PPM 2 0 8 6 4 PPM 2 0 150 100 PPM 50 0 150 100 PPM 50 0 88. This is a clear difference that would allow one to distinguish these two compounds. 89.
OH (a) HO 38.Chapter 28 36. H (a) (R) OH (S) H OH (b) O (S) OH (S) (S) H OH OH L-ribose (c) (R) OH (S) (R) O OH O OH OH OH D-xylose L-threose OH . O H (R) (CHOH)n CH2OH glycose OH OH (a) HO OH OH (d) HO2C OH CO2H (e) HO2C OH OH CHO OH OH (d) HO OH OH OH (f) HO OH CHO OH CHO (e) HO OH OH O (b) HO OH OH OH OH OH O OH (c) HO OH OH CH2OH (CHOH)n CH2OH glycitol CO2H (CHOH)n CH2OH glyconic acid CO2H (CHOH)n CO2H glycaric acid OH CHO (CHOH)n CO2H uronic acid OH CO2H OH OH CHO (b) HO OH OH (c) HO OH CHO OH OH OH CHO 37.
OH O H HOEt Bu Bu H H H .OH (d) HO L-allose (g) (S) (S) (S) OH (S) OH O H (e) HO (S) (S) (R) OH (R) OH O H (f) HO (R) (S) (R) OH (S) O H OH OH L-mannose OH OH OH (R) (R) OH D-idose OH OH HO (S) (R) O H L-talose OH OH 39.EtOH Bu Et Bu H Bu Et O H H Et -H+ Bu +H+ Et hemi-acetal H . O (a) HO OH (b) HO HO -L-xylofuranose OH (e) HO OH -L-mannopyranose OH HO OH -D-idopyranose OH HO O OH (f) HO HO -L-talofuranose OH HO O OH (c) HO HO -D-allofuranose O OH HO O OH OH OH OH OH -D-arabinopyranose HO (d) O .H2O Bu Bu Et O H Et O H Et O Bu H + EtOH .H+ H + H+ Bu Et Et O H O OH + H+ H -H+ •• •• O + H+ H O H O O O 50 O acetal 40.
-D-glucopyranosyl-(1 1). O OMe O OMe O (a) HO OH HO OH HO OH (b) HO OH OH O -D-psicopyranose OH OH O -D-tagatopyranose -L-ribulofuranose HO HO OH (c) HO (d) HO O OH -L-fructofuranose HO HO 43.90% .-D-allopyranose HO (b) HO HO -D-altropyranose OH O O OH -D-galactopyranose O OH HO OH O. and since % + % = 1.38% = +18. 44. % (-128) = -72. Therefore. Therefore.-D-altropyranosyl-(1 4). % = 1-% .56. % = 56% and % = 44%.41. (1-% )(+90) + % (-38) = +18 = 90 . and % (-128) = 18 -90. The anomeric is not effective on C3. % (+90) + % (-38) = +18. so % = -72 / -128 = 0. 42. only on C2.-D-galactopyranose . so the equatorial conformation on the right should be favored. HO -D-glucopyranose HO (a) HO OH OH O O OH -D-allopyranose OH O OH O.
HO OH -D-glucopyranose OH O OH (c) HO HO O O OH OH HO O.-D-Fucf-(1 4). -D-lyxopyranose OH O (a) HO -D-fucofuranose OH HO O HO O HO O O OH OH -D-altropyranose OH O.-D-talopyranosyl-(1 1).-D-Xylp-(1 1).-D-Frup HO OH -D-ribulofuranose OH .-D-mannopyranose 45.-D-glucopyranose HO -D-talopyranose (d) HO HO -D-idopyranose O O HO OH O OH -D-mannopyranose OH O.-D-Ribf-(1 4).-D-Altp HO -D-xylopyranose (b) O O HO O HO O O OH -D-fructopyranose HO OH O.-D-Lyxp-(1 1).-D-idopyranosyl-(1 4).
-D-Altf-(1 4). HO (a) HO OH -D-arabinofuranose OH HO (b) HO OH -D-fucofuranose OH HO O (c) HO -D-galactofuranose O (d) HO HO -D-arabinofuranose OH OH OH -D-galactopyranose OH aq.-D-Idop OH 46. CuSO4 Na tartrate HO HO CO2–Na+ OH O O OH HO O O OH HO -D-mannopyranose OH OH AgNO3 NH3 O aq.-D-Allp-(1 1). CuSO4 Na tartrate HO OH HO OH OH -D-gulopyranose OH HO O O HO OH CO2–Na+ HO HO O O O AgNO3 NH3 HO OH HO HO HO O O OH CO2–Ag+ HO HO no reaction .-D-allopyranose HO HO (c) HO HO HO O O HO OH -D-altrofuranose O O O HO OH -D-idopyranose OH O.
Ni(R) HO HO OH OH OH (j) HO HO OH OH -D-glucopyranose OH OH .HO (e) HO O OH AgNO3 OH NH3 HO HO OH CO2–Na+ OH OH O (f) HO OH O (g) HO OH HO (h) HO HO HO (i) HO OH O OH O OH -D-galactopyranose OH aq. aq. NH4Cl OH -D-rhamnopyranose HO OH HO HO D-talofuranose Br2 . KMnO4 OH -D-lyxopyranose OH 1. NaBH4 2. pH 5 HO HO OH OH CO2H OH OH OH OH HO OH O OH Na/Hg OH OH OH OH HO OH CO2H OH -D-allopyranose OH H2 .
H+ HO O OH Et2SO4 O OAc OAc OAc O OEt EtO EtO OEt OEt O OEt OH OH O O OH OH HO O OH OH O . Draw the major product for each of the following reactions. O OH HO Ac2O . cat. H+ O HO O OH -D-altropyranose OH EtOH . NaOAc AcO (a) HO OH AcO -D-glucopyranose OH HO (b) HO OH HO (c) HO OH HO (d) HO HO O (e) HO OH OH D-arabinopyranose Ph OH D-idofuranose OH PhCHO . H+ O O OH D-talopyranose OH acetone .HO (k) HO O OH HNO3 HO HO OH CO2H OH OH OH D-idopyranose OH 47.
aq. NaOH 3. NH3 4. aq. NH3 OH (R) OH OH (R) (R) (R) (R) (R) (R) CHO 4. NH2OH 2. aq. OH (a) (R) OH 1. ZnCl2 3. Ac2O . aq. Ac2O . NH3 4. ZnCl2 3.48. NH2OH 2. OH (a) (R) OH (R) (S) CHO 1. ZnCl2 CHO 3. NH3 4. (R) H3C OH O (R) (S) OH CHO N CHO OH 2. ZnCl2 CHO 3. H+ OH (R) OH (R) CHO OH OH (b) OH OH OH CHO 1. H+ OH CHO OH OH (d) (R) OH OH 1. aq. ZnCl2 3. aq. NH2OH 2. H2SO4 OH OH . NH 3 OH (R) OH (S) (S) CHO 4. H+ OH OH OH (R) (S) (S) CHO OH OH O OH OH 49. NH3 4. Ac2O . H+ OH OH OH (R) (S) OH OH (c) (R) OH OH (S) (R) CHO 1. Ac2O . NH2OH 2. Ac2O . NH2OH 2. aq. Ac2O . H+ OH OH OH OH OH (R) (S) (S) (S) 1. H+ OH OH OH (R) (R) (S) OH (R) (S) (S) CHO OH OH (e) OH (f) (R) OH OH (S) (S) OH OH (R) OH 1. ZnCl2 CHO 3. NH2OH 2.
H2SO4 O OH OH O (R) OH (R) (R) OH (R) (R) OH CHO OH CHO 1. H2SO4 OH 50. NaOH 3. HO (R) O HO (S) (S) (R) 1. Ac2O . CHO H3C N OH (R) O 2. CHO OH O (R) OH (S) H3C N CHO OH OH OH (c) (R) 2. NaOH 3. aq. aq. H3C N OH OH 2. AcOH AcO (R) O (R) 1.OH (b) (R) OH (S) O 1. HBr . H2SO4 O OH OH (d) (R) OH (R) (S) 1. H2SO4 O CHO OH OH (f) (R) OH OH (S) (S) OH OH O (R) OH OH (S) (S) 1. H2SO4 O OH OH OH (R) (S) 1. Br AcO (R) (R) (R) O (S) (R) AcO OH (S) AcO (R) OAc HO HO AcO OAc . aq. Cl3CN 2. NaOH 3. aq. H+ 2. CHO H3C N OH CHO OH OH OH 2. aq. CHO H3C N OH O (R) OH (R) (S) OH CHO OH OH OH (e) (R) OH OH (S) (R) 2. NaOH 3. NaOH 3.
AcO (R) AcO AcO O O (S) (R) (S) (R) (R) (S) (R) HO (R) HO HO O O (S) (R) (S) (R) (R) (S) (S) AcO H3O+ O (R) HO (S) O AcO AcO OAc HO HO OH O.-D-Araf-(1 4). 52. A (a) P 5' CH2 3' 9-( -D-ribofuranoyl)adenine H OH OH 1-( -D-ribofuranoyl)uracil A CH2 3' P 5' G T (b) G OH 3' P 5' P U OH 3' P 5' C OH 3' P 5' T 3' P 5' T OH 3' P 5' A OH OH 3' OH 5' CH2 CH2 3' 3' P P OH 5' 5' .-D-Idop O N (a) HO O H H OH H H OH H N N Me NH NH2 (b) HO O H OH H O N N H O H OH O NH 9-( -D-ribofuranoyl)guanine NH2 N (c) HO O H H OH H H OH N N N (d) HO 1-( -D-ribofuranoyl)thymine O H H H N O 51.
OH 3' P C OH 3' P 5' A 3' P 5' C OH 3' P 5' C OH OH 3' OH 5' NH2 N O -O N N N NH2 N N NH2 N H HO O P OH O H OH O H H OH N O N O H H OH O O H HO P O- P O- N O H H OH O (a) O NH O -O P O- O H H OH O H N O N O NH N NH2 Me H O O P OH O H OH O H H OH N O O NH HO O P OO H H OH N O H (b) .G (c) P 5' 53.
At best the . .OH will be converted to the -methoxy compound and the .O Me O O P OH (c) O H OH O O H HO P OH O H OH O O H HO P OH O H OH O H H OH N O N O Me N O Me NH O NH O NH 54.or the . NaOAc HO OH NaN3 THF AcO OAc O N3 H2 .and -methoxy compounds.sugar precursor. Pd AcO OAc OH AcO OAc O NH2 H O+ 3 OAc HO OH OAc O OAc Hbr AcO OAc O OAc NH2 O Br OAc OH 56. probably not as prominent as with the oxygen substituent. there will an anomeric effect with the nitrogen.OH will be converted to the -methoxy compound. Presumably. 55. It depends on whether it is the . mutarotation of the sugar will lead to a mixture of . but it is anticipated that the amine will prefer the axial position. At worst. O O OH NH2 O HO HO OH HO HO HO OH HO OH HO NH2 OH OH O OH Ac 2O .
59.OH OH Na(Hg) O OH NaBH4 HO OH OH HO OH OH OH OH HO OH OH 57. NH3 HO O OH OH O OH 58. OH OH OH AgNO3 . OH OH KMnO4 OH OH OH O F (a) –O PO 3 NH2 NH N O (c) N O H H OH NH2 N O Cl O H H H OH N (f) O O H H OH H H OH N Ph H N N N N O H H OH H H OH (b) HO H –O PO 3 H H OH Ph OH OH (d) –O PO 3 O O H H OH H N N (e) –O PO 3 O O H H OH H N N –O PO 3 H OH H OH .
6 + 3. (1-% )(+112) + % (+19) = +53 = 112 . (1-% )(+90) + % (-38) = +18 = 90 .38% = +18. % = 1-% .2(+19) = 89.(g) –O PO 3 N O H H OH H H OH O (h) –O PO 3 Cl N O H H OH H H OH (i) N –O PO 3 Ph O O H H OH H H OH N 60. 61.90% . Therefore. OH O -xylopyranose HO HO OH O OH HO HO OH major at equilbrium HO OH O HO -arabinopyranose HO HO OH O 62. OH major at equilbrium OH 63. % (-93) = -59. % (+112) + % (+19) = 0. Therefore. % (-128) = -72. and since % + % = 1.112. % (+90) + % (-38) = +18.8 = 93.5°C. % = 1-% . so % = -72 / -128 = 0.112% +19% = +53. and % (-128) = 18 -90. The base-paired anti-parallel strands for A-G-G-T-A are: . If -D-rhamnose has a specific rotation of –17° and -D-rhamnose has a specific rotation of +31. and the specific rotation of the mixture is +9° at equilibrium. so % = -59 / -93 = 0. Therefore.4° % (+112) + % (+19) = +53. % = 63% and % = 37%. and since % + % = 1. % = 56% and % = 44%.63.8(+112) + 0. that is the percentage of and at equilibrium? Draw the structure that predominates at equilibrium. and % (-93) = 53 .56. Therefore.
H N N NH2 OH H O OH H H O OP O O OH H H O N HN O H O OP O H H O H2N HN N N N O H2N O HN H O N O P OH O H OH O O H H O P OH O H OH O H H O O P OH O H OH N O H H OH N N N O NH2 N NH NH2 N N NH O NH2 O N N N N N N O O N NH N NH2 N O OH H H O OP O H H O O OH H H O OP O H H O O OH H H OPO3– N N H NH2 N –O PO 3 N N O H H OH O H N H O P OH O H OH O H N N H2N N N N O O O HO OH P HO O O P HO O O P HO O N O N N N O O HO OH P HO O H2N O H N N O O O O HO OH HO P HO O O P HO O N O H N O O O O OH P HO O 64. .
O O Me N N Me Me N N H HO H OH Me N N H H OH Me N N O O O 66. .H2O OH OH H+ HO HO HO OH OH OHC O OH -D-glucose O OH 1. 1. H+ OH 2.O N O -O H N N N P O- O H H OH O H H OH 65.H2O OHC O OH . OH 2.7-trimethyl-1H-purine-2.6(3H.3. H+ 2. . HO HO OH H+ H O H2O O OH 1. -H2O HO HO OH OH2 OH -H+ O OH HO HO OH HO OH O tautomerize OH HO HO OH OH O O HO HO HO O -H2O HO HO 1.H O 2 HO O -D-fructose OHC O OH O OH 1.7H)-dione 67. . H+ 2.
100 PPM 50 0 150 100 PPM 50 0 .Spectroscopy Problems. These problems involve carbohydrates or nucleotide derivatives. 100 PPM 0 100 50 PPM 0 NH2 N HO O H H OH H H OH H N N N HO O H OH N N NH2 N N H this CH will 2 show that is unique 8 6 4 PPM 2 0 8 6 4 PPM 2 0 150 69. Do not attempt these problems until the concepts in Chapter 14 have been mastered. IR: aldehyde H a 2815 cm–1 glucose HO OH aldehyde H OH H OH OH O HO glucopyranose HO OH OH O OH 10 5 PPM 0 6 4 PPM 2 0 aldehyde C 200 68.
D-Glucitol -D-Xylose Thymidine Mmethyl -D-glucopyranoside . 72. 73. 71.70.
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