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Answers To Chapter 1 In-Chapter Problems.
1.1. The resonance structure on the right is better because every atom has its octet. 1.2. O– O

CH2+

CH2

CH2

CH2

C

O

C

O

NMe2

NMe2

NMe2

NMe2

NMe2

NMe2

N

N H3C N CH2 H3C

N H3C N H3C CH2

N

N

the second structure is hopelessly strained O O

3. 1. C(1–3) and C(6–9) are the keys to numbering. C9–O12. 1. 1 6 7 8 2 4 3 5 12 11 9 10 O 9 8 7 1 2 3 6 OH Ph 13 H+. C9–C13. Because the pKb of HO– is 15.4.5. sp2 sp sp O sp O 2 O– sp2 sp3 sp3 CH3 sp2 sp3 sp3 sp3 CH3 CH3 sp3 N all sp2 Ph N all sp2 sp2 sp2 sp2 Ph H3C CH3 H3C sp3 F F B sp2 sp2 O sp3 H sp2 sp H sp2 F H2C CH3 H H 1. Break C4–C6. One lone pair resides in the p orbital and is used in resonance.7.6. C6–C11. (a) No by-products. 12 13 14 15 16 19 18 7 4 5 OMe6 22 17 24 25 H HN 11 1 10 9 2 3 20 15 14 13 1 24 O 21 Br 16 12 11 17 21O 20 8 19 7 18 6 25 Br 8 Br Br Br 2 3 9 N 10 4 Me Br OMe 23 OMe O5 1. C6 and Br25 are left over. Break O5–C6. C9–C11. (b) Make C8–N10. The O atom in furan has sp2 hybridization. PhC≡CH has a pKa ≤ 23 and BuC≡CH has pKa > 23. C8–C9. (a) Make C4–O12.Chapter 1 2 1. so make a bond between them and call it the by-product. . H2O O 12 5 4 Ph 11 13 O10 H (b) After numbering the major product. C12–Br24. the other resides in an sp2 orbital and is not used in resonance. PhC≡CH is much more acidic than BuC≡CH. C11–O12.

but the C–H bond α to the ketone must be broken. The OH is more acidic (pKa ≈ 17) than the C α to the ketone (pKa ≈ 20). .Chapter 1 3 1.8. Because the by-product of the reaction is H2O. there is no need to break the O–H bond to get to product.

H3C H O O –H + H3C O O H3C O O (f) Both imidazole and pyridine are aromatic compounds. which has its lone pair in an sp2 orbital that is perpendicular to the aromatic system. a product is obtained for which two good resonance structures can be drawn. (a) Both N and O in amides have lone pairs that can react with electrophiles. so it is much more important than normal. Protonation of this N gives a compound for which two . When the O reacts with an electrophile E+. (d) A resonance structure can be drawn for 1 in which charge is separated. is the basic one. only one good resonance structure can be drawn for the product. (c) Exactly the same argument as in (b) can be applied to the acidity of acyl chlorides versus the acidity of esters. This is not true of 4.Chapter 1 4 Answers To Chapter 1 End-Of-Chapter Problems. Loss of an acidic H from the γ C of 3 gives a structure for which an aromatic resonance structure can be drawn. Upon addition of a nucleophile to either an ester or a ketone. The lone pair of the H-bearing N in imidazole is required to maintain aromaticity. When the N reacts. a tetrahedral intermediate is obtained for which resonance is not nearly as important. 1. (e) The difference between 3 and 4 is that the former is cyclic. but in this case the two rings are made aromatic. so the other N. E reaction on O R O N R R E R O N R R O R E N R R reaction on N (b) Esters are lower in energy than ketones because of resonance stabilization from the O atom. Normally a charge-separated structure would be a minor contributor. As a result it costs more energy to add a nucleophile to an ester than it does to add one to a ketone. so the difference in acidity between acyl chlorides and esters cannot be due to inductive effects and must be due to resonance effects. and therefore the tetrahedral product from the ester is nearly the same energy as the tetrahedral product from the ketone. Note that Cl and O have the same electronegativity.

However. – Nu Nu aromatic non-aromatic (h) The tautomer of 2. so the S(p)–C(p) overlap in PhS– is much smaller than the O(p)–C(p) overlap in PhO–. The reduced overlap in PhS– leads to reduced resonance stabilization. In cyclopentadienone. not electrophilic. a nonaromatic compound. is phenol. + – (i) Carbonyl groups C=O have an important resonance contributor C–O. (k) Attack of an electrophile E+ on C2 gives a carbocation for which three good resonance structures can be drawn.Chapter 1 5 equally good aromatic resonance structures can be drawn. H N N + H H N HN HN H N (g) The C=C π bonds of simple hydrocarbons are usually nucleophilic. when a nucleophile attacks the exocyclic C atom of the nonaromatic compound fulvene. so the presence of a Ph ring makes less of a difference for the acidity of RSH than it does for the acidity of ROH. [Common error alert: Many cume points have been lost over the years when graduate students used cyclohexadienone or cyclopentadienone as a starting material in a synthesis problem!] (j) PhOH is considerably more acidic than EtOH (pKa= 10 vs. By contrast. protonation of pyridine gives an aromatic compound for which only one good resonance structure can be drawn. the electrons from the C=C π bond go to the endocyclic C and make the ring aromatic. an aromatic compound. H H 2 H E+ H E O H H E O H H E O O H H H H H H H H . 17) because of resonance stabilization of the conjugate base in the former.4-cyclohexadienone. Attack of an electrophile E+ on C3 gives a carbocation for which only two good resonance structures can be drawn. this resonance contributor is antiaromatic. S is larger than O.

(e) The N(sp2) lone pair derived from deprotonation of pyridine is in lower energy orbital.Chapter 1 H H E + 3 6 H E H H O H H E H H O H O H H 2. (a) O F3C OH (b) In general. deprotonation of 7-membered ring gives anti-aromatic anion. AH + is more acidic than AH Cl3C OH O inductive electron-withdrawing effect of F is greater than Cl N H2 (c) O EtO (d) O CH3 N H O H3C O CH3 Ketones are more acidic than esters Deprotonation of 5-membered ring gives aromatic anion. than the N(sp3) lone pair derived from deprotonation of piperidine. hence more stable. NH NH2 .

even when the anion of the latter can be delocalized into a Ph ring. CO2Et CO2Et (h) EtO2C CO2Et EtO2C Anions of 1.Chapter 1 (f) Acidity increases as you move down a column in the periodic table due to increasing atomic size and hence worse overlap in the A–H bond 7 PH2 NH2 (g) The anion of phenylacetate is stabilized by resonance into the phenyl ring. The anion of 3-nitrophenol can't do this. OH H3C O NH2 More electronegative atoms are more acidic than less electronegative atoms in the same row of the periodic table .3-dicarbonyl compounds are stabilized by resonance into two carbonyl groups CO2Et (i) OH O2N O N – O2N OH – The anion of 4-nitrophenol is stabilized by resonance directly into the nitro group. Draw resonance structures to convince yourself of this. O N O O O – – O (j) O H3C (k) Ph CH3 Ph H C(sp) is more acidic than C(sp3).

especially where halides are concerned. good electrophile. (Electrons go around in circle. (m) this C atom O this C atom The C(sp2)–H bond on the upper atom is the plane of the paper. no metal. Broken: C4–C3. (Air.Chapter 1 (l) O O 8 The anion of the latter cannot overlap with the C=O π bond. (AIBN tips you off. (Os) (c) Polar. hence cannot delocalize. an overall transformation can sometimes be achieved by more than one mechanism. (Nitric acid. so polar acidic mechanism is a . no metal.) 4. (Electrons go around in circle. MeO Br 6 5 4 OMe 3 2 1 7 Bu3 SnH cat. AIBN MeO OMe H 4 5 3 2 1 7 6 CO2Me CO2Me + Bu3 SnBr (b) Ag+ is a good Lewis acid. orthogonal to the p orbitals of the C=O bond.) (i) Pericyclic. basic. Sn7 and Br6 are missing from the product. (f) Pericyclic. (Electrons go around in circle. allyl bromide is electrophile. No nucleophile or electrophile.) (e) Free-radical. so there is overlap with the C=O orbitals. (Ethoxide base. Good nucleophile.) Yes.) (m) Pericyclic. basic.) (d) Polar. basic. No nucleophile or electrophile. Sn7–Br6. (LDA is strong base. (Catalytic peroxide tips you off. No nucleophile or electrophile. Made: C5–C3. No nucleophile or electrophile. (k) Pericyclic. no metal. so the C=O bond provides no acidifying influence. The C(sp3)–H bonds on the lower atom are in and out of the plane of the paper. hence is not made acidic by the carbonyl group. 3.) (b) Metal-mediated. no metal. Clearly it’s not acting as a nucleophile in this reaction.) (h) Free-radical.) (j) Metal-mediated. so they’re probably bound to one another in a by-product. C5–Br6. (a) The mechanism is free-radical (AIBN). (Electrons go around in circle. acidic.) (g) Polar.) (l) Polar. (a) Free-radical. (Fluoride ion is a good base.

Broken: C13–C8.Chapter 1 9 reasonable guess. Ag–Cl. Made: C3–C10. RT Me Me 5 O7 O9 Me H 11 7 1 13 12 Me H 11 (f) The mechanism is polar under basic conditions (NaOEt). 8 1 Cl 7 6 5 4 11 10 2 3 6 N + 12 O 13 9 AgBF4 9 4 5 7 2 1 O 10 11 13 3 12 NH from water HBF4 AgCl 8 O (c) This mechanism is also pericyclic. Broken: O3–C4. RSO3H CH2Cl2. C7–C13. C7–Cl8. One of the H’s in H2O goes with the BF4–. Made: C1–C7. O3– C6. Ph3P 2 1 O OMe NC CO2Me Ph CO Me 2 8 (e) The mechanism is polar under acidic conditions due to the strong acid RSO3H. and CH3 groups as anchors for numbering the atoms. but mechanism is actually pericyclic (bonds forming to both C10 and C13 of the furan and C3 and C7 of the enamine). O2–C4. The mechanism is polar under basic conditions. C3–C11. Two equivalents of cyanoacetate react with . Made: C13–C6. Use the carbonyl. Broken: N1–C2. very stable AgCl. O1 H3C7 4 11 12 5 3 11 5 4 6 3 2 ∆ 9 6 8 10 O1 2 12 H3C 7 9 OSiMe 3 8 10 Me3SiO H (d) Ph3P is a Lewis base. C2–O (water). while the other is attached to N1 in the by-product. 14 13 12 9 Me OH 5 8 10 6 14 4 6 8 10 3 Me 2 1 4 3 Me O Me 2 cat. it must get together with Ag to make insoluble. it must come from H2O during workup. 5 O 4 OMe 3 6 7 8 5 O 4 6 7 3 O Ph 1 2 + CN cat. Me3SiO. Broken: C2–C8. An extra O appears in the product. Made: C2–C12. Cl8 is missing from the product.

There are two CH3 groups in the starting material. C4–O6. Broken: C1'–C2'. C2–C12. 5 4 8 7 1 2 3 11 13 16 5 H3C Me3SiO 6 CH3 15 7 CH3 3 O 12 14 O 9 Li . 1/2 BrCH2 CH2Br 5 6 EtO2C NH2 3 1' 2' 3' 4' CN + EtO2C OEt 6 (g) Polar under acidic conditions. aq. C9–C14. C2'–C6. C2–O3. Use these as anchors to decide the best numbering method. Broken: C3–C12. The H can come from EtOH or HOH. EtOH. Broken: O3–C4. Made: C2–C7. The Me groups provide clues as to the numbering. NaHCO3 4 6 H 2 1 14 15 16 10 9 10 12 H H 11 13 OH CH3 (i) The carboxylic acid suggests a polar acidic mechanism. C5–Br. At first the numbering might seem very difficult. but the mechanism remains fundamentally unchanged from a solution phase mechanism. O7–Si8. Broken: C15–O16. The two products differ only in the location of a H atom and a π bond. C12–C15. The enzyme serves to guide the reaction pathway toward one particular result. warm to RT. C1'–OEt. so the CO2Et is bound to EtO or HO. Made: C1–C6.Chapter 1 10 each equivalent of dibromoethane. 1 1 3 4 4 2 5 EtO2C 2 CN NaOEt. . then pericyclic. C2–C15. and two in the product. their numbering is the same. C6–Br. C2'–C3. Me 5 4 3 1 2 6 7 8 9 15 10 11 12 14 13 Me 5 6 1 3 2 16 7 8 Me Me OPO3 PO3– H+ enzyme Me 10 11 4 9 Me 14 15 Me Me Me Geranylgeranyl pyrophosphate H H 13 12 Me A Taxane (h) Two types of mechanism are involved here: First polar under basic conditions. Made: C1– C14. One of the CO2Et groups from cyanoacetate is missing in the product and is replaced by H. C5 and C16. Made: C2–C5.

10. as it remains attached to C3. so they are probably connected to one another in a by-product. remain attached to it in the formate product. Br 6 2 1 3 4 5 7 8 10 9 11 6 2 3 4 1 9 5 8 10 11 7 Bu3 SnH Ph cat. with the two H’s in H2O coming from C8. Made: C5–C8. as C10 is the only C that has a different number of H’s attached in S. Again. and product. O4 is still missing. and the reaction involves changes in π bonds. This is a pericyclic mechanism.11 10 9 2 O3 O O O4 3 1 8 6 CH3 CH3 7 HO H3C 5 (l) Polar mechanism under basic conditions. However. H12 appears connected to C10 in the product. AIBN + Bu3SnBr Ph H H H (k) No acid or base is present. C7 remains attached to C8 and O6 in the product. Made: C1–C9. but the middle O is different from the end O’s. Broken: C1–C2. the two O’s attached to C2 in the S. O3–O4. NaOH 6 8 7 CH3 CH3 11 10 9 HO H3C 8 + HCO2 – 2 1. Made: C1–O11. it’s not clear which O in ozone ends up attached to which atom in the product. C2–C6.Chapter 1 3 11 O3 Bn 1 N 2 H 6 O Me 8 6 7 O H Bn N C 1 2 Ph 4 5 OH O 4 7 Ph Me Me 8 Me O5 (j) Free-radical mechanism (AIBN). Broken: C2–C7. O4– C5. C5–O6. Br7–Sn11. Broken: C6–Br7. C2–O9.M. it is clear where O4 ends up. C2–O10. Both Br7 and Sn11 are missing from the product. C2 leaves as formate ion. it’s probably lost as H2O. use C11 with its two Me groups as an anchor to start numbering. 11 1 2 3 HO H3C 5 4 8 6 CH3 CH3 7 9. Use C8 with its two Me groups as an anchor to start numbering. C1–O4. Ozone is a symmetrical molecule. O4 5 CH3 O O 6 11 CH3 2 7 9 10 5 3 1 aq. O9–O10.3 4 + H2O O .M.

Use C6 as an anchor to begin numbering..1) for an explanation. C4 and C7. it is probably C4.M. Acidity is a measure of the difference in energy between an acid and its conjugate base. . C7 is next to C6 in the S. A (d) A (j) N (p) N (v) none (bb) N (hh) N (e) A** (k) A (q) none (w) none (cc) N. Made: C2–C7. A= acidic. In the S. **The O atom still has a lone pair. there are two CH2 groups.Chapter 1 12 (m) Bromine undergoes electrophilic (polar acidic) reactions in the absence of light. since the CH2 group in the product is not next to C6. †The fact that an elimination reaction can occur upon removal of H+ from this atom (with loss of the leav- ing group next door) is irrelevant to the question of the acidity of this atom. E= electrophilic. N (y) A (ee) none (kk) N (b) none* (h) N (n) E (t) E (z) E (ff) N (ll) E (c) E (i) none (o) A (u) E (aa) A (gg) E. but if it were to use it in a nucleophilic reaction. (a) E (g) none† (m) none** (s) A. The conjugate base formed by removing H+ from this atom would be very high in energy. N= nucleophilic. Broken: Br–Br. C3–Br.M. 4 3 2 1 7 4 H 5 6 O Br2 Br 1 3 5 2 6 7 H O 5. it would acquire a very unfavorable +2 formal charge. while C4 is not. A (ii) none (f) E (l) E (r) N (x) N (dd) N (jj) N (mm) slightly A? *See text (Section B. The one CH2 group in the product must be either C4 or C7.

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