MCAT Organic Chemistry Er) 4.4. IUPAC Parent chain: longest C chain w/highestorder functional group, should have lowest possible # ‘normal, straight-chain alkane iso: terminal Pr group (|-CHMe,), or common structural isomer ‘sec: functional group on 2° Cin 4-carbon chain (e.g, sec-butyl, |-CHMe-CH,-CH,) tert. functional group on 3° C (eg, tert-butyl, I-CMe,) neo: terminal ‘Bu group 1.2, Hydrocarbons, Alcohols wakanes Glen 9, H-CH) > Meth. th. prop... But... pent.., Mex... ept-.., Ot... NOR... 8 ‘Alkenes: C=C double bond (e.g. H.C=CH.) ‘Alkynes: C=C triple bond (e.g., H=CH) ‘Aromaticty ©. Huckel's rules: S259, planar, eye, conjugated Alcohols: hydroxyl (/-OH) group © Diols: 2 hydroxyls = Glycols: aliphatic dots = Geminal diols/nydrates: hydroxyls on same C, spontaneously dehydrate into carbonyls 4 Vicinal cits: hydroxyls on adjacent C's ‘© Aldehydes (...-l, 0x0...) terminal carbonyl ([-C=O) group © Formaldehyde: CH,O (methanal) © Acetaldehyde: MeCHO (ethanal) © Propionaldehyde: E{CHO (propanal) ‘© Ketones (..-one, oxorketo-...): non-terminal carbonyl group © Acetone: Me;CO (propanone) © @-...:C adjacent to carbonyl Be Yoon, Bun OC. © Enone: a.8-unsaturated carbonyl = Conjugated system© Ethers (alkoxy-..., yl .-yl ether: R-O-R' © Furan, tetrahydrofuran (THF), dioxane, ete 1.4. Carboxylic Acids ‘Carboxylic acids (..-oic acid, ..-cate): terminal COOH group © Formic acid: HCOOH (methanoic acid) © Acetic acid: MeCOOH (ethanoic acid) © Propionic acid: EXCOOH (propanoic acid) © Dicarboxylc acids (..dioic acd, dicate): 2 terminal }-COOH groups ‘Oxalic acid: HOOC-COOH (ethanedioic acid) 11 Malonic acid: HOOC-CH,-COOH (propanedicic acid) s_Succinic acid: HOOC-CH,-CH,-COOH (butanedioic acid) CA derivatives © Esters (cate): replace hydroxy! w/ alkoxy ({-OR) group 1 Esterfying group: R bonded to © = Lactones (...lactone): cyclic esters ‘© c-acetolactone (3-membered), B-propiolactone (4-membered), etc. © Amides (..-amide, N-.., NN..): R-CONRz, replace hydroxy! w/ amino (|-NR) group a= Lactams (.. lactam): cyclic amides ‘© B:lactam (4-membered), ylactam (6:membered), etc. © Anhydrides (oie anhycride): dehydration between 2 CA groups 1.5. Functional Groups Priority: most — least oxidized © Alkenes = alkynes © Alkenes > alkynes in cyclic compounds CAs: ..-oi¢ acid, carboxy. Anhydrides: anhydride, alkanoyloxycarbony. Esters: cate, alkoxycarbony ‘Amides: ..-amide, carbamoy/amido- Aldehydes: al, oxo Ketones: ..-one, oxolketo- ‘Alcohols: «ol, hydroxy”. ‘Alkenes: ..-ene, alkenyl Alkynes: ..-yne, alkynyb. Alkanes: ..-ane, alky!-2. Isomers 2.4, Structural Isomers ‘© Structural/constitutional isomers: same molecular formula ‘© Usually dif. physica/chemical properties '= Physical properties: no change in composition ‘© Density, solubiity, meitingrboling point, color, etc. = Chemical properties: reactivity, changes composition ‘© Functional groups 2.2. Stereoisomers © Stereoisomers: same molecular formula, connectivity ‘© Conformational isomers/conformers: interconvert by rotating around a bonds ‘© Newman projection: see molecule along C-C bond axis Staggered: no overlaps, antiperiplanar ‘© Anti 2 largest groups are on opposite sides, lowest energy, most stable Gauche: 2 largest groups are adjacent 1» Eclipsed: overlapping, synperiplanar ‘© Totally eclipsed: 2 largest groups overlap, highest energy, least stable Cyclic conformations. = Ring strain ‘Angle strain: nonideal bond angles ‘© Torsional strain: eclipsed/gauche interactions ‘© Sericinonbonded strainivan der Waals repulsion: nonadjacent groups occupy same space © 1,3:diaxialflagpole interactions: axial-axial steric effects = Cyclohexanes ‘© Chair: axial-equatorial orientations altemate, most stable ‘© Bulkiest group favors equatorial to minimize 1,3-diaxial interactions © Chair lp: chair = half-chair = twist-boat = boat = © Configurational/optical isomers: interconvert only by reforming bonds © Chirality: handedness ‘= Chiral center: C w! 4 diff. groups © Enantiomers: opposite configuration at every chiral center ‘= Same physicalichemical properties, dif, optical acivties/chiral reactions ‘= Optical activity: rotation of plane-polarized light by chiral molecule ‘© Rotates to the right/CW: dextrorotatory (4...) (+) ‘© Rotates to the left(CCW: levorotatory (..). (-)Specific rotation: [aJS@IRVEL, where c = concentration (im), = path length (dm) 1 Racemic mixture: equal [enantiomers no optical activity Separate by adding chiral resolving agent fects to convert enantiomers ito diastereomers © Diastereomers: 22 stereogenic centers = Difl physical, offen dif. chemical properties = Gis-transigeomettc isomers: around immovable bonds or rings, = Meso compounds: have chiral centers, but also intemal plane of symmetry (achiral, no optical activity) 2.3. Relative, Absolute Configurations Relative coniguation: wert. another chiral molecule (enantiomers, aastereomers,cistrans, etc) © Absolute conformation: exact spatial arrangement ((E)/(Z), (R)(S), etc.) © Cann-Ingold-Preog (CIP) pron rules: Figher atomic # = higher proty Double-bond configuration: assign pristies © (2): 2 highest priory groupe ere on same side of double bond © (E): on opposite sides + Chiral centers: assign prone, rotate molecule so lowest pity group i in back ° @rsghvew 9 (8) leticcw ©. Fischer projection: horizontal (out fom page), vertical into page) 1 flowestpronty group is honzatal, then chirality is opposite what we get = Swiching 2 groups on achiral center fips chirality Rotating chiral center 80° fips chirality ‘© Principal (n): size, © Shells/energy levels. ‘© Azimuthal (I: shape, 0m 3.3. Hybridization ie a iad eee he ‘© sp* single bonds © 25% s, 75% p character © Tetrahedralvent (109.5°) ‘© sp double bonds, 1 unhybridized p orbital © 33% s, 67% p character © Unhybriaized p orbital —-m bond © Trigonal planar (120°) ‘© sp: triple bonds, 2 unhybridized p orbitals © 50% s, 50% p character © 2unhybridized p orbitals -- 2 m bonds © Linear (180°) ‘© Resonance structure: potential - arrangement in molecule © e density: weighted avg, ofall resonance structures, © Conjugated system: connected p orbitals w/ delocalized e”, alternating single/double bonds © Some resonance structures may be more favoredPrneceiene Acids, Bases © Lewis © Acid: e° acceptor, electrophile, vacant p orbital" atom to accept e” (all Bransted-Lowry acids) © Base: e donor, nucleophile (all Bransted-Lowry bases) © Bronsted-Lowry © Acid: H’ donor © Base: HY acceptor > Ampholeri: either acid or base, depending on environment «Aci dissociation constant Ki=[HEIIAAIIAL B20 K, © Strang (pK, < -2), weak (-2 § pk, $ 20) ‘© Functional groups © Acids: alcohols, a-H of carbonyls, CAsiderivs. © Base: amines/amides Nucleo} ‘Nucleop! ‘© Nucleophile (Nuc): lone pair’ bond forms new bond w/ electrophile Lewis bases More (-) charge: e density t —+ nucleophilicity + Less EN: atom more likely o share e- > nucleophilcity © Smaller molecule: steric hindrance | — nucleophiliity © Protic solvent: protonates NucIH-bonding -» nucleophilicty | 1» Polar protic: nucleophiliity + from top to bottom (EN elements bond wi H* instead of accessing electrophile) 1» Polar aprotic: nucleophilicty 1 from bottom to top (nucleophilic «» basic) = Nonpolar: no nxn. (rts. cant dissolve) ‘© Electrophile: (+) charge/6" accepts new bond from nucleophile > Lewis acids © More (+) charge, better LG — electrophilicity + ‘© Leaving group (LG): product that keeps e” after heterolysis (opposite of coordinate covalent bonding) © Good LGs: weak bases (conj. bases of strong acids), resonance-stablized, EWG inductive effects © Convert hydroxides into better LGs w/ MsCl or TsCl ‘* Nucleophilic substitution: R-LG broken, R-Nuc formed © Sy1:LG leaves (rate-limiting), Nuc attacks resutting carbocation 1» Needs stable carbocation (3° > 2° > 1°), weak Nuc, polar protic solvent (stabilizes carbocation) Rate = K{R-LG), 1st order = Usually racemic product (carbocation intermediate is achiral)© $\2: Nuc attacks, LG leaves (concerted) = Sterically unhindered substrate (1° > 2° > 3°), strong Nuc, polar aprotic solvent (no H-bonding w/ Nuc) ss Rate = k{Nuc][R-LG}, 2nd order = Stereospecific: backside attack, inverts chirality © Elimination: G-H, C-LG broken, C-C 1 bond formed © Et: LG leaves (rate-limiting), base deprotonates adjacent C to form double bond ‘= Similar conditions as yt = Weak base w/ heat © E2: base removes H antio LG, double bond forms, LG leaves (concerted) = Similar conditions as $2 = Strong base w/ heat, H must be antito LG © Zaitsev's rule: more substituted alkene is favored Except in E2 when this is stereochemically impossible (H not anti to LG) = Except w/ bulky base (e.g, 'BUOK, EtLN), where steric hindrance favors less substituted alkene 4.3, Redox Reactions ‘© Oxidation: ox. state f, lose e°, lose H/gain O ‘© Reduction: ox. state {, gain e”, gain Hilose O ‘© Oxidizing agents: high e° affinities, high ox. states © Strong: Cr (VI) (H.CrO,, K,Cr,OxIH,SO,, CrOyH,SO,acetone, etc), KMNO, © Weak: PCC, CrO,/pyridine © Oxidation = Ketones ~ (mCPBA) esters Aldehydes ~(H,CrO, or KMnO, or H,0;)-» CAS 1 alcohols ~ (PCC or CrO./pyridine)-» aldehydes 1% alcohols ~ (H,CrO, oF KMnO,)— CAS 2! alcohols ~ (PCC of CrO,/pyridine or H,CrO, or KMnO,)—> ketones, Vicinal diols ~(HIO, or NalO, or Pb(OAc},)-+ 2x aldehydes (cleaved C-C bond) = Alkenes ~ (O80, or KMnO,/base)— vicinal diols © Ozonolysis = Reductive workup: alkenes (0, then (Zn or Me,S))~+ aldehydesiketones ‘= Oxidative workup: alkenes ~ (O, then H,0,, or KMnO,/acid/A)-» CAstketones © Alkynes ~ (0; then H,0;, or KMnO,/acid/A)—» CAs © Epoxidation = Alkenes ~ (mCPBA)-» epoxides ‘© Reducing agents: low EN/IE, metal hydrides, transition metals (many ox. states) © Strong: LAH, BH./THF (but very selective, only on CAs) © Weak: NaBH,, DIBAL-H, LTBA© Reduction w= Aldehydes ~ (LAH or NaBH,}~ 1° alcohols = Ketones - (LAH or NaBH.) 2” alcohols, (CAs ~(BHJTHF then acid)— 1° alcohols CAsiesters (LAH then water)—> 1” alcohols, Esters ~ (DIBAL-H then acid)- aldehydes ‘Amides ~ (LAH then acid) amines ‘Acid chlorides ~ (LTBA)— aldehydes ‘© Selectivity (xn. prefers 1 product over others), specificity (xn. produces only 1 product over others) © Regloselectivity’specificity,stereoselectivity/speciity, etc. ‘© Chemoselectivity:cxn. prefers 1 functional group over others Location © More oxidized group: CAs/esters > aldehydesiketones > alcohols/amines © Carbonyl C: 6° due to oxygen’s EN, acidic a-H due to keto-enol tautomerization © S\1:3°> 2" > 1° C (more stabilized carbocation) © §)2:1°>2° > 3°C (less steric hindrance) ‘© Steric protection © Block nucleophile access, disfavor $2 © Protecting group: temporarily disable leaving group © CAderiv. reactivities: acid chlorides > anhydrides > CAs/esters > amides > More reactive derivs. can form less reactive dervs., but not vice versa ans 5.1, Properties © General formula: R-OH ‘© Physical properties, © H-bonding: metting/boling points 1, (ag) solubility | = More hydroxyls = more H-bonding © Weakly acidic: alcohol = alkoxide + H" = Resonance in phenols = more acidic = e-withdrawing groups (EWGs): stabilize (-), more acidic = e-donating groups (EDGs): destabilize (-), less acidic © eg. alkyls© Synthesis © Reduce aldehydesiketones w/ LAH or NaBH, © Reduce CAsiesters w! LAH 5.2, Reactions © Oxidation © PCC (pyridinium chlorochromate): partially oxidizes alcohols 1° aldehydes, 2° — ketones © Nowater > cannot hydrate to oxidize further = 3° alcohols are unreactive: can't break C-C bond © Cr (Vb: fully oxidizes alcohols 1° CAs, 2° — ketones _Na,Cr,0;, H:Cr0,, Crs, ete. + H:S0, © Mesylatesttosylates © MsOH (methanesulfonic acid, MeSO,H) = Mesylates: MsCl + ROH / base -> MsOR © TSOH (p-toluenesulfonic acid, MePhSO;H) 1s Tosylates: TSC! + ROH /base + TOR © Tur hydroxyls into good L@s © Protecting groups for hydroxyls ‘© Acetalization © Acetals: RHC(OR), = 1°+ diols + cat, acid -+ acetals © Ketals: R.C(OR), = 2° diols + cat. acid -» ketals © Protecting groups for hydroxyls (e.g., LAH reduction) 5.3, Phenols Phenol: hydroxyl + aromatic ring © o1thon.. (O-..), Meta. (M-.), Para... (Pr) ‘* More acidic than usual: resonance stabilizes (-) charge ‘© Quinones (oxidized) = phenols (reduced) © Hydroxyquinones: quinones w/ hydroxy! groups: = Hydroquinone: benzene-1,4-diol © Phylloquinone (vitamin K,), menaquinone (vitamin K;) © Ubiquinoneicoenzyme Q (oxidized) = ubiquinol (reduced)EEC ‘© General formula: HRC=O (aldehydes), R © Physical properties © Strong dipole: carbonyl O is EWG = Carbonyl C (6°) is good electrophile © Smaller | in metingrbilng points than alcohols: no H-bonding > Aldehydes are more reactive than ketones: les steric hindrance, no e~donating alkyl © Synthesis © Aldehydes: partially oxidize 1° alcohols wi PCC © Ketones: oxidize 2° alcohols © Reduce esters w/ DIBAL-H (Bu-AH) © Reduce acid chlorides w/ LTBA (LIAH(O'BU),) 6.2. Nucleophilic Addition Polarized C=O makes carbonyl C a good electrophile ‘© Nuc addition: tetrahedral intermediate Ino good LG, then proton transfer: {O° —» [OH IF there is a good LG, then carbonyl re-forms. © Hydration ‘© Water as Nuc, forms geminal dials (1,1-diols) © Needs cat. acidibase ‘© Acetalization © Hemiacetalsiketals: }OH, |-OR = Aldehydes/ketones + 1 eq, alcohol —- hemiacetals/hemiketals = Alcohol (Nuc) attacks carbonyl C © Acetalstketals: |-OR, |-OR 1» Aldehydes/ketones + 2 eq, alcohol/anhydrous acid —+ acetalsiketals = Sy1 mechanism: protonated }-"OH, leaves © Revert to aldehydes/ketones w/ aq. acid/A. © Imine/enamine: tautomers © Imines: RN=CR, (thermodynamically favored) ‘= Condensation: aldehydes/ketones + amines (cat, acid)—> imines ‘© + hydroxylamine (H.N-OH) -» oximes © + hydrazine (H.N-NH,) — hydrazones ‘© + semicarbazide (H,N-NH-C(O)NH,) ~» semicarbazones (ketones)© Enamines: R,N-C(R)=R (kinetically favored) ‘Cyanohydrins © HCN=H" +-CN (Nuc) © Aldehydes/ketones + cyanide + cyanohyarins = Stabiized by new C-C bond sox © Oxidation © Aldehydes (ox. agent stronger than PCC)» CAs = Cr(ViH,SO,, KMnO,, gO, H.0, © Ketones cannot be oxidized further: 2° C can't hold more bonds ‘© Reduction © Aldehydes/ketones ~ (red. agent) alcohols = LAK (ithium aluminum anhydride, LiAIH,), NaBH, (sodium borohydride) 7. Enolates ‘© Enolate: aldehyderketone w/ deprotonated o-C. ‘© GH acidity: resulting carbanion is stabilized © Induction: carbony/ 0 is EWG, pulls €- density away from CH bonds © Resonance stabilization w/ carbonyl: distributes (-) charge to EN O atom © Ketone < aldehyde acidity, due to alkyl (EDG) Steric hindrance ‘Ketone < aldehyde reactivity to Nuc’: alkyl > H size, higher-energy intermediate needed ‘© Strong base (e.g., “OH) needed to form enolate 1.2, Tautomerization ‘© Keto-enol tautomerization © Keto (thermodynamically favored) = enol (kinetically favored) © q-racemization: any aldehyde/ketone w/ chiral a-C becomes racemic © Michael addition: deprotonated 1,3-dicarbonyl (Nuc) attacks enone, forms C-C bond = 1,3:dicarbonyl 2 EWGs, very acidic o-H 1» Also works with EWGs other than carbonyls. ‘© Kineticithermodynamic enolates © Kinetic: double bond to less substituted a-C, less steric hindrance to form= Formed faster, less stable © Rapid, reversible rans, at ow temps ‘© Strong, sterically hindered base © Thermodynamic: double bond to more substituted a-C, hyperconjugation from more substitution ‘= Formed slower, more stable ‘© Slow, reversible rans. at high temps: kinetic product reverts to rxts. and forms thermodynamic product © Weak, small bases Imine-enamine tautomerization © Imine (thermodyriamically favored) = enamine (kinetically favored) L 1 Condensation ‘© Aldol: carbonyl, w/ hydroxyl on B-C ‘© Aldol condensation © Steps w= Aldehydelketone ~ (cat. base)— enolate = Enolate + aldehyde/ketone -» aldol = Aldol (strong base/A)— enone © E1/E2 mechanism © Most useful when aldehyde/ketone self-reacts ‘= W/ multiple aldehydes/ketones, either can act as Nuclelectrophile > mixed product © Except wi 4" o-C (e.g., benzaldehyde, PhCHO), which can't deprotonate and must be electrophile © Retro-aidol reaction © Aldol =(aq. base/A) = aldehydesiketones = Needs stable enolate intermediate Carboxylic Acids 8.1, Properties ‘General formula: R-COOH Dicarboxylic acid: 2 |-COOH groups ‘© Physical properties, > Polar, H-bonding: both carbonyl and hydroxyl =” Melting/boiling point +, dimerization © Very acidic (for an organic acid) resonance-stabilized anion = EWGs: stabilize (-), more acidic © eg. ENO, +X= EDGs: destabilize (-), less acidic eg. HNH,, -OMe © Dicarboxylic acids PK, ; > pK, 2: deprotonate both H's — mutually repelling (2-) anion = Bedicarboxylic acids: very acidic a-H, resonance: stabilized by both CA groups ‘© But til less acidic than the |-COOH's. Reactions © Synthesis © Fully oxidize 1° alcohols/aldehydes w/ Cr (VI/H,SO,, KMnO,, Ag,0 © React acid chloride w/ water ‘© Nucteophilic acyl substitution ‘© Nuc attacks carbonyl to form tetrahedral (-) intermediate, carbonyl re-forms as LG leaves © Acyl derivatives: CAs, amides, esters, anhydrides, etc. = Amides: CA++ amine ~ (acid or base)» amide © Resonance:stabilized: between C=O and N’ 1 Fischer esterification: CA + alcohol ~ (acid) ester * Protonate carbory/, alcohol is Nuc = Anhydrides: 2 CAs —(A)-> anhydride ‘© Reduction w/ LAH — 1" aleohol © NaBH, is too weak to reduce CAs © Decarboxylation © 1,3-dicarboxylic acid/B-keto acid —(A)-» keto-enol © Cyclic intermediate is stable ‘© Saponifcation © Falty acid + “OH — soap = e.g, riacylalycerol + NaOH — FA salts + glycerol © Soaps (amphipathic) self-arrange into micelles ree eed ‘9.1, Amides, Esters, Anhydrides ‘© Amides: formed by (CA or acid chloride) + NH/1"/2° amine © Least electrophilcireactive of CA derivs.: Nis ED ‘© Esters: formed by Fischer esterification (CA + alcohol), or by (anhydride or acid chloride) + alcohol ‘© Anhydrides: formed by CA condensation, or by CA + acid chioride© Very electrophilicireactve: resonance: stabilized, 3 0's (EWGs) ‘© Acid chlorides: formed by CA + (SOC!, of PCI, or PCI, oF (COC)./OMF) ‘© Most electrophilicreactive of CA derivs.: Clis EWG and very good LG Reactiily: acid chlorides > anhydrides > CAslesters > amides © Stability © 1" C's canit undergo S41, 1 © Steric hindrance © 3° C's cant undergo $,2, only Sy1 © Aldehydes/ketones can be protected from ren. using acetals/ketals Electronic effects © Induction: dipole across o bond, less EN (6°) to more EN (6) 1 More 6°: more reactive to nucteophilc attack = EDGs: add e- density, more nucleophilic, stabilize (+), more basic © Lone pairs on atoms (OIN), alkys, 6°, ete #orp-directing (also halides) = EWGs: remove e- density, more electrophilic, stabilize ( ‘© Atoms bonded to more EN atoms, halides, & et. # meirecting (except halides) © Conjugation: “alternating” singlefmutiple bonds, delocalized 1 system in parallel unhybricized p orbitals, 1 Stabilize (+) from Nuc bonding, more reactive to nucleophilic attack © Ring strain: torsional (eclipsing interactions), angle (compressed sp) strain 1 More strain if2 rings are fused Very reactive more acidic ‘© Anhydride cleavage: Nuc attacks a carbonyl C, proton transfer by middle O, CA leaves © Acid anhydride + NH, > amide + CA © Acid anhydride + alcohol ester + CA, © Acid anhydride + water -» 2 CAs ‘© Transestetfication: alcohol (Nuc) displaces esterifying group © R-COOR'+ R'-OH = R-COOR' + R-OH © Needs anhydrous environment to avoid forming CA ‘© Amide hydrolysis: amide + water (acid or base)» amine + CA © Acidic conditions: acid protonates carbonyl O, water (Nuc) attacks carbonyl, amine leaves © Basic conditions: “OH (Nuc) attacks carbonyl, amine leaves (much worse LG) © Amides are relatively unreactive, need cat. acidibase to hydrolyzeCTC ee eee en 10.1. Amino Acids, Peptides, Proteins ‘Amino acids (AAS) © General formula: H,N-C(HR)-COOH = Amino group, a-C, R group (side chain), CA group >All AAS are chiral L-isomers, (S) configuration = Except Gly, which is achiral = Except Cys, which is (R) bic |-CH,-SH changes priority order © Amphoteric (both acidic and basic): amino is basic, CA is acidic ‘= Zwitterion in solution: both charges form © Categories 1» Nonpolar: hydrophobic, inward in proteins ‘© Nonpolar nonaromatic: Gly, Ala, Val, Leu, 's0, Pro, Met ‘©. Saturated hydrocarbon side chains, except Gly (|-H), Met (}-CH,-CH,-SMe) ‘© Aromatic: Trp, Phe, Tyr (has hydroxy!) = Polar: hydrophilic, outward in proteins ‘© Neutral: Ser, Thr, Asn, Gin, Cys © Hydroxyl, amide, thiol groups ‘© Negativelacidic: Asp, Glu © Terminal deprotonated CAs ‘© Positiverbasic: Arg, Lys, His > Protonated amino groups * Proteins © Peptide bond: |-C(O)-NH- 1s Resonance-stabilzed: rigid C-N bonds, stable protein backbones ‘Ads = polypeptides 10.2, a-Amino Acid Synthesis ‘= Strecker synthesis: aldehyde ~ (NH,CVKCN)—> aminonitile ~ (aq, acid)» AA © Mechanism 1» S,2/condensation: ‘NH, protonates carbonyl, NH, (Nuc) attacks carbonyl C, imine forms as {-H.0" (LG) leaves = Nuc addition: ON attacks protonated imine, forms aminonitrile = Hydrolysis: nile protonated, 2 eq. water (Nuc) attack nitrile C, hydroxyl forms carbonyl as |-NH," (LG) leaves © R group of aldehyde becomes R group of AA= Ketones: form a.a-disubstituted AAs (2 R groups) © Starting aldehyde is achiral -+ racemic product ‘© Amidomalonate synthesis: phthalimide + diethyl bromomalonate ~ (® base, @ R-X, @ aq. base/A, @ aq. acid/A)—+ AA © Mechanism = S,2: phthalimide (Nuc) attacks diethyl bromomalonate, 8 (LG) leaves ‘Bulky Nuc, steric hindrance to prevent multiple substitutions in substrate = Strong base deprotonates a-C of phhalimidomalonic ester, forms resonance-stabilized carbanion = S,2: carbanion (Nuc) attacks R-X, halide (LG) leaves = Hydrolyze wi strong base + A, spit into phthalic acid + dicarboxylic acid (H.N-CR(COOEt),) = Decarboxylate 1,3-dicarbonyl w/ strong acid/A, form AA © Diethyl bromomalonate provides AA backbone, R-X provides R group © Catbanion ester is achiral —» racemic product ‘© Gabriel synthesis: phthalimide — (0 base, 2 R-X, @) H,N-NH,)-» 1" amine (R-NH,) 10.3. Phosphorous Compounds ‘= Phosphoric acid: H.PO, 9 HPO, (in strong acid) = H,PO, = HPO,* = PO,* (in strong base) © Diff. pk, for removing each H ~» good buffer ‘© Inorganic phosphate (P): HPO,*, H,PO, © Exists in equal amis. at physiological pH 7.4 © Pyrophosphate (PP): P.O," ‘© Phosphodiester bond: }-R-O-PO;-O-R- © Links 5-C sugars of nucleotides 1» Nucleotide phosphates (e.g., ATP), deoxyribonucleic acid (ONA) © Energy storage w/ nucleotide phosphates 1 Electrostatic repulsion: adjacent (-) phosphate groups = Resonance-stabilzed (-) charges © DNAelongation = Releases PP,— 2, = Hydrolysis provides energy for phosphodiester bond formation Cees 14.4, Infrared ‘© Pass infrared (IR) light thru sample, then measure absorbance ‘¢ Measures molecular vibrations: bond stretching, bending, etc© Vibration must cause change in bond dipole moment to exhibit absorption 1» No IR spectra for 0, (no dipole), HC=CH (symmetric), etc. ‘© IR spectrum: transmittance (%) vs. wavenumber (cn) © Wavenumber: = Standard range: 4,000 to 400 on Fingerprint region: 1,500 to 400 cm’, absorbance pattem is characteristic for each molecule ° where = absorbance (ont), T= transmittance (3) ‘© Characteristic absorptions ‘© O-H: broad 3,300 cm for alcohols, broad 3,000 cnr” for CAS = CA carbonyl pulls some e density away from alcohol © NCH: sharp 3,300 em™* © C=O: sharp 1.750 om" © Any atom bonded to H has high wavenumber © C-H: sp (3,300 cm") > sp? (3,100 em) > sp" (3,000 em) 14.2, Ultraviolet-Visibi ‘= Pass ultraviolet (UV) light thru sample dissolved in inert, nonabsorbing solvent, then measure absorbance ‘© Measures extent of conjugation: more conjugated —> lower transition energy -> longer J, smaller ¥ © Conjugated molecules: unhybridizea p orbitals © Most useful for molecules w/ double bonds, heteroatoms w/ Ione pairs in conjugated systems. ‘© © transition: tinonbonging e- can be excited to higher-energy antibonding MOs ‘© From highest occupied MO (HOMO) to lowest unoccupied MO (LUMO) © Lower HOMO-LUMO energy gap — more easily excited e” longer J, smaller # ‘© Place sample in a magnetic field © Studies nuclei w/ magnetic moments (odd atomic number, odd mass number or both) © asstate (lower energy): some nucle's magnetic moments align w/ field © Bstate (higher energy): iradiate nuclei w/ radiofrequency pulses of energy gap, some a-state nuclei are excited into B state ‘© Absorption depends on atoms’ magnetic environments © Energy absorption vs. chemical shift (ppm) = Chemical shift (0: frequency, increases right to left (downfield) © Reference peak: tetramethyisilane (TMS, SiMe) is at 0 ppm ‘© Proton ('H) NMR: resonance 010 ppm downtfeld from TMS © Chemically equivalent: same magnetic environment, same peak = Area under peak (= peak height) « # H's = More surrounding EWGs ~» less e density on H -» more deshielded H —» downfield peak= More surrounding EDGs —+ more e" density on H — more shielded H —+ upfield peak © Spin-spin coupiing/spilting: muttiplet peaks = Hcanbe ina or B state, so a nearby H (3 bonds away) can experience 2 dif, magnetic environments n+ I tule: ifm H's are 3 bonds away from a H, then its signal is split into n + | peaks © Except O-H of N-H © Coupling constant (/): magnitude of spiting (Hz) = e9,,1,1-dibromo-2-chloroethane (H'Br.C-CH®,Cl) H. Hy's can be ag, aB/Ba, BB —» triplet peak of 1:2:1 He:H, can be a or 8 doublet peak © Chemical shif ranges = Alkanes (3p"): 0-3 ppm = Alkynes (sp): 2-3 ppm Alkenes (sp): 46-6 ppm = Aromatics: 6-8.5 ppm = Aldehydes: 9-10 ppm = CAs: 10.5-12 ppm ‘© Magnetic resonance imaging (MRI) © T1 curve: radio energy released by spins over time © T2 curve: precessing spins fall out of synchrony over time Pane eee ‘* Extraction: move dissolved solute into a better solvent © “Like dissolves like" = H-bonding: more aqueous 1» Dipole-dipole, van der Waals forces: less aqueous Procedure 1» Mix2 immiscible solvents, wait for aqueous and organic phases to separate = Use separatory funnel (w/ stopcock) to isolate the denser phase on bottom = Rotary evaporator (rotovap): evaporate solvent, isolate product © Multiple extractions are more effective ‘© Fitration: isolate residue (solid) from ftrate (liquid) © Gravity: solvent falls thru fter, desired product is in liquid © Vacuum: force solvent thru fier, solid is desired product‘© Recrystalization: dissolve product in minimum amt. of hot solvent, then lett recrystallize ‘© Product is soluble only at high temps of solvent © Removes impurities 12.2. Distillation ‘Separates 2 liquids of dif. boiling points thru evaporation/condensation ‘© Simple distlaion: BPs < 150°C, at least 25 °C diff. in BP © Procedure = Heat mixture inside distiling flask at low temp, liquid w! lower BP vaporizes first \apor travels up the distilation column, then condenses inside water-cooled condenser = Collect condensate into distillate inside receiving flask © Superheating: gas bubbles can't overcome atm. pressure + surface tension, liquid exceeds BP wio vaporizing = Avoid by using boiling chip, magnetic stirer, etc. ‘© Vacuum distillation: BPs > 150°C © Vacuum = ambient pressure |, liquids BPS | © Distills mixtures wio degrading product ‘© Fractional dstilation: < 25 °C dif. in BP © Fractionation column between distiling flask and condenser © SA = vapors condense on inert objects and re-evaporate ‘© Higher up the fractionation column = higher proportion of liquid w! lower BP 12.3. Chromatography. ‘= More similar to surroundings —- more adhesion to stationary phase —> slower elution thru mobile phase © Put sample on stationary phase/adsorbent (solid), and run mobile phase/eluent(lquid/gas) thru it © Sample elutes into mobile phase and migrates, adheres to stationary phase © Partitioning: mobile = stationary phases equilibrium ‘© Thin-layer chromatography (TLC), paper chromatography ‘© Separate by polarity: more nonpolar = further up the plate ‘= Polar stationary phase: silica (TLC) or cellulose (paper) = Nonpolar mobile phase: weakly polar organic solvent = Reverse-phase chromatography: nonpolar stationary. polar mobile phase © Procedure ‘= Spot sample spot on plate, then develop plate by placing it upright inside developing chamber in pool of eluent ‘Spots travel upward by capillary action = Stains: UY, iodine, phosphomolybdic acid (PMA), vaniln, ete TY Uv chromophores’ Socbeipe tons, coseny,sougaled syste «Retardation factor f= (lt. ave by spo) (ast saver Fon) © Preparative TLC: use large plate for purification‘© Column chromatography ‘© Same principle as TLC. = Polar stationary phase: silica/alumina beads = Nonpolar mobile phase © Procedure = Mixture travels down column by gravity ‘© Flash column chromatography: speed 1 by forcing solvent down wi pressure = Collect dif. fractions that leave column, then purify © lon-exchange chromatography: charged beads = Retain oppositely charged compounds in column, then elute wi salt gradient © Size-exclusion chromatography: porous beads = Small compounds get stuck in pores, travel slower = Large compounds travel faster © Affinity chromatography: protein-binding beads ‘= Retain specific protein in column, then elute by breaking ligand-protein bonds ‘© Free receptors/targets/antibodies to compete wi bonding ‘© pH/salnty to disrupt bonds ‘© Gas chromatography (GC), vapor-phase chromatography (VPC) © Crushed metal/polymer stationary phase, HeIN; (gas) mobile phase © Procedure 1» Inject volatile mixture into coiled column, compounds adhere to column indifferent places = Inject pure compounds into mass spec ‘¢ High-performance liquid chromatography (HPLC) © Polar stationary phase, nonpolar mobile phase = Reverse-phase HPLC (RP-HPLC): nonpolar stationary phase, polar mobile phase © Similar to column chromatography, except wi sophisticated solvenvtemp gradients © Historically, similar to GC, except w/ pressurized liquid as mobile phase