TABLE 18-1 Some Common Classes of Carbonyl Compounds

Class General Formula Class General Formula O O ' ' ketones R9C9R aldehydes R9C9H O O ' ' carboxylic acids R9C9OH acid chlorides R9C9Cl O O ' ' 9 9 9 9 9 esters R C O R amides R C NH2

AAALBKS0 Figure Number: 18 00.01 T01 ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E length energy ketone CObond 1.23 Å 178 kcal/mol R (745 kJ/mol) 120° C O R 120° alkene C C bond 1.34 Å 146 kcal/mol (611 kJ/mol)

AAALBKV0 Figure Number: 18 00.04 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E O O 9 9 9 9 9 9 9 CH3CH2CH2CH3 CH3 O CH2CH3 CH3CH2 C H CH3 C CH3 CH3CH2CH2 OH butane methoxyethane propanal acetone 1-propanol bp 0°C bp 8°C bp 49°C bp 56°C bp 97°C

O 1685 cm1 O 1690 cm1 O 1745 cm1 O 1815 cm1 C CH3 H

acetophenone 2-butenal cyclopentanone cyclopropanone

AAALBLM0 Figure Number: 18 00.22 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E a carbon a carbon a carbon O O O R CH2 C H R C CH3 R C CH2R dd2.4 9–d10 d2.1 d2.4 an aldehyde a methyl ketone other ketones

C a bg H CH2 CH2 CH3 7 Hz splitting distance 7 Hz splitting distance

9.8d 9.7d 2.5d 2.4d

10 9 8 7 6 5 4 3 2 1 0 d (ppm)

H3C CH2CH2CH2CH2CH3 30

208

200 180 160 140 120 100 80 60 40 20 0

+ + . CH3 C CH2CH3 CH3 C O CH2CH3 43 radical cation acylium ion ethyl radical m/z 72 m/z 43 (base peak) loss of 29

+ O .

+ + . CH3 C CH2CH3 CH3CH2 C O CH3 57 radical cation acylium ion methyl radical m/z 72 m/z 57 loss of 15 100 43 80 O

60 CH3 C CH2CH3

40 abundance M 72 20 57 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 m/z

AAALBLT0 Figure Number: 18 03 ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E ©2003 by Prentice Hall, Inc. A Pearson Company 160 3 CH . 150 loss of 15 + + 2 140 CH 3 loss of 28

g H 130 C H + CH 2 . . C O 3 CH + 120 2 CH H ab 2 CH 110 CH 57 2 C O z / 44 (base peak) m CH loss of 43 z 100

H . 2 / m + stabilized cation + CH 90 + H C H O z 29 /

80 . C O . z m . . / C M m AAALBLU0 72 72 H z 70 / H m 60 57 28 + + . . 3 3 50 44 M CH CH 2 40 CH 2 57 2 72 CH z 29 / CH 30 m 2 cleavage C O 29 γ 20 CH , β McLafferty rearrangement McLafferty H C O 10 0

80 60 40 20

100 abundance H Figure Number: 18 04 WADE ORGANIC CHEMISTRY, 5E g hydrogen OH+ + . O H . H C H H OH.+ H C C H C H H H C = + C C C HH C C C C H H H H H H HH H H H ethylene enol m/z 72 loss of 28 m/z 44 McLafferty rearrangement of butyraldehyde

R .+ O H + H R O H + . O C . a b g A B R R' C C C CR = B R' CC + CC C C A B R A A B B R C R' B enol loss of alkene A A McLafferty rearrangement of a general ketone or aldehyde

AAALBLW0 Figure Number: 18 05 ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E + − + − p* p* C O CO − + forbidden − + allowed n C O + + p nonbonding C O orbital − − "allowed" transition "forbidden" transition e ≅ 5000 – 200,000 e ≅ 10 – 200

Primary alcohols : aldehydes

OH O O & 9 [oxidizing agent] 9 9 [overoxidation] 9 9 R CH2 −2 H R C H [O] R C OH primary alcohol aldehyde carboxylic acid

CH3 (1) O3 O (2) Me S 2 O

H 1-methylcyclohexene 6-oxoheptanal (65%)

R is alkyl or aryl; G is hydrogen, a halogen, or an activating group. G O O C Cl

AlCl3 O2N O2N p-nitrobenzoyl chloride p-nitrobenzophenone (90%)

AAALBMM0 Figure Number: 18 07.12 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E R H O H 2+ + Hg , H2SO4 H RCC H CC RCC H H2O HO H H alkyne enol (not isolated) methyl ketone

Example

H O C HO H C C H SO , Hg2+ + 2 4 CC H CH H 3 H2O

ethynylcyclohexane enol cyclohexyl methyl ketone (90%)

AAALBMO0 Figure Number: 18 07.14 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E RH O − (1) Sia2BH OH RCC H CC RCH2 C H (2) H2O2, NaOH H OH alkyne enol (not isolated) aldehyde

Example H O C C CH2 C H (1) Sia2BH

(2) H2O2, NaOH

ethynylcyclohexane cyclohexylethanal (65%)

H H H 1,3-dithiane, pKa 32 dithiane anion

AAALBMY0 Figure Number: 18 07.25 P18.6 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E H , HgCl2 R X O H O S S S S 2 alkylating agent H R (primary alkyl halide) H R H aldehyde dithiane anion thioacetal

PhCH2 CH2CH2CH3 PhCH2 H PhCH2 CH2CH2CH3 1,3-dithiane thioacetal thioketal ketone

AAALBNB0 Figure Number: 18 07.28 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E O O OLi OH O LiOH R9Li H3O H2O R9C9OH R9C9O Li R9C9OLi R9C9OH R9C9R R R carboxylic acid lithium carboxylate dianion hydrate ketone

cyclohexane cyclohexyl phenyl ketone carboxylic acid

dianion hydrate

AAALBND0 Figure Number: 18 07.30 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E R′ Mg X R′ MgX R′ H R′ H O H 3 RCN C N C N C O NH4 R R R nucleophilic attack Mg salt of imine imine ketone

benzonitrile phenylmagnesium bromide benzophenone imine benzophenone (magnesium salt) (80%)

AAALBNH0 Figure Number: 18 07.35 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E O O Li AlH(O-t-Bu)3 R9C9Cl R9C9H lithium aluminum tri(t-butoxy)hydride acid chloride aldehyde

CH3 O CH3 O CH3 O SOCl Li+ −AlH(O-t-Bu) 9 9 2 9 9 3 9 9 CH3CHCH2 C OH CH3CHCH2 C Cl CH3CHCH2 C H isovaleric acid isovaleroyl chloride isovaleraldehyde (65%)

AAALBNL0 Figure Number: 18 07.39 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E O O ' ' + 9 9 9 9 + 9 + R2 CuLiR C Cl R C R R Cu LiCl a lithium dialkylcuprate (Gilman reagent)

O ' Example O C ' Cl C

(1) Li Cl ( (CuLi (2) CuI 2

80%

Nuc Nuc H R δ+ δ− − H Nuc C O C O C O + Nuc − R R R R R nucleophilic attack alkoxide product

CH3 CH3 CH3 H H H O C O O C O H H O C O H H O 2 3 CH3 H2O H CH3 CH3 attack by water loss of H acetone hydrate

AAALBOG0 Figure Number: 18 07.60 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Basic conditions (strong nucleophile) Step 1: Addition of the nucleophile. Step 2: Protonation. & & & H9Nuc

Nuc C"O Nuc9C9O Nuc9C9O9H Nuc & & & Reverse reaction: & − & Nuc &

Nuc9C9O9H Nuc9C9O Nuc C"O & & &

Acidic conditions (weak nucleophile, activated carbonyl) Step 1: Protonation. Step 2: Addition of the nucleophile.

+ − H H − &

& & & H Nuc & & Nuc

C"O C"O C9O Nuc9C9O9H

& & & &

Reverse reaction:

& H H

& & & & &

Nuc9C9O9H Nuc C"O C O C"O

& & & & Nuc9H

R R Ph CO CPPh R R Ph ketone or aldehyde phosphorus ylide

R R C C Ph3P O R R alkene

AAALBON0 Figure Number: 18 07.68 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Ph H d Ph P C dCH 9Li H H 2 Ph R C4H10 Ph Ph CH2CH2CH3 butane Ph P H C X Ph P C H butyllithium Ph Ph R R Ph H LiX triphenylphosphine alkyl halide X Ph P C phosphonium salt Ph R phosphorus ylide

Examples Br 9 Bu Li Ph3P CH3 Br Ph3P CH3 Ph3P CH2 methyltriphenylphosphonium salt ylide

Br 9 Bu Li Ph3P Ph CH2 Br Ph3P CH2 Ph Ph3P CH Ph benzyltriphenylphosphonium salt ylide

AAALBOO0 Figure Number: 18 07.69 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Step 1: The ylide attacks the carbonyl. Step 2: The betaine closes to a 4-membered ring. H R Ph3P O Ph3P O Ph3P C CO H C C R H C C R R R R R R R ylide ketone or aldehyde a betaine oxaphosphetane

AAALBOP0 Figure Number: 18 07.70 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Step 3: The ring collapses to products. Ph3P O Ph3P O H R H C C R C C R R R R four-membered ring triphenylphosphine oxide alkene

AAALBOQ0 Figure Number: 18 07.71 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E R R OH [hydrate] CO H O C K 2 [ketone][H O] R R OH 2 keto form hydrate (a geminal diol) Example

O HO OH CH3 C CH3 H2O CH3 C CH3 K 0.002 acetone acetone hydrate

AAALBOX0 Figure Number: 18 07.78 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E In acid Step 1: Protonation. Step 2: Water adds. Step 3: Deprotonation. H O O O H O H H3O C C R C R R C R RR RR O O H H2O HH H3O

H2O

AAALBOY0 Figure Number: 18 07.79 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E In base Step 1: Hydroxide adds. Step 2: Protonation. O O OH HO H O H C HO C R HO C R OH RR R R

AAALBOZ0 Figure Number: 18 07.80 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Step 1: Cyanide adds. Step 2: Protonation. O O O H CN H CN C R C R R C R RR CN CN ketone or aldehyde intermediate cyanohydrin

AAALBPD0 Figure Number: 18 07.84 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E O OH H C R NH2 C C H2O primary amine ketone or aldehyde R N H R N carbinolamine imine (Schiff base)

AAALBPI0 Figure Number: 18 07.89 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Step 1: The amine adds to the carbonyl. Step 2: Protonation and deprotonation. O O O H H3O C C C R N H R N H

H2O carbinolamine R NH2 H nucleophilic attack fast proton transfer

H H H O O C C C H+ C C N N H2O N H3O N N RH R H R minor major R H R H carbinolamine protonated intermediate (all octets filled) imine

9 Z in Z NH2 Reagent Product

9 9 & " 9 HH2N H ammonia C N H an imine

9 9 & " 9 RH2N R primary amine C N R an imine (Schiff base)

9 9 & " 9 OH H2N OH hydroxylamine C N OH an oxime

9 9 & " 9 NH2 H2N NH2 hydrazine C N NH2 a hydrazone

9 9 & " 9 NHPh H2N NHPh phenylhydrazine C N NHPh a phenylhydrazone O O O ' ' ' 9 9 9 9 & " 9 9 9 NHCNH2 H2N NH C NH2 C N NH C NH2 semicarbazide a semicarbazone

AAALBPT0 Figure Number: 18 08.009 Summ ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E O H+ RO OR C 2 R OH C H2O R H R H aldehyde acetal O H+ RO OR C 2 R OH C H2O R R R R ketone acetal (IUPAC) ketal (common)

AAALBQE0 Figure Number: 18 08.018 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E The first half is an acid-catalyzed addition to the carbonyl Step 1: Protonation. Step 2: Alcohol adds. Step 3: Deprotonation.

CH3 OH H H H O O O H HO O HO OCH 3 CH3 9 H OTs O CH3

ketone protonated (activated) ketone hemiacetal

AAALBQG0 Figure Number: 18 08.020 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E The second half begins like an acid-catalyzed dehydration Step 4: Protonation. Step 5: Loss of water. H CH3 CH3 CH O O H CH O O H O O 3 3 H+ H2O

hemiacetal protonation, loss of water resonance-stabilized carbocation

Step 6: Second alcohol adds. Step 7: Deprotonation. H H CH3 O CH3 O CH3 O O CH3 CH3 O O CH3 CH O H 3 9 9 CH3 O H H attack by methanol acetal

AAALBQH0 Figure Number: 18 08.021 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E H H H C C H O O O H H C C H H H H CCH H2O HO OH benzaldehyde benzaldehyde ethylene glycol ethylene acetal

Examples O O Na2Cr2O7 CH3 CH C H CH3 CH C OH dil H2SO4

CH3 CH3 isobutyraldehyde isobutyric acid (90%) O O C C H Ag2O OH THF/H2O

(97%)

Zn(Hg), HCl or H2NNH2, KOH O H OH HH NaBH4 (1) TsCl R C R R C R R C R or LiAlH (2) LiAlH ketone4 alcohol 4 methylene group

AAALBRO0 Figure Number: 18 08.059 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Step 1: Deprotonation from N. Step 2: Reprotonation on C. H − R R N OH R N R N H2O N C N H C N H C N H H C N H R R R R hydrazone remove proton from N replace proton on C OH

AAALBRS0 Figure Number: 18 08.063 UN ©2003 by Prentice Hall, Inc. WADE A Pearson Company ORGANIC CHEMISTRY, 5E Step 3: Remove second proton from N. Step 4: Lose N2. Step 5: Protonate. NN − R OH R R R N N H2O H C N H H C N H C H C H OH R R R R carbanion product

O N O O N HOH 2C HOH 2C N H H H H H H H H OH H OH H

deoxycytidine deoxyadenosine