Aldehydes and Ketones

Transcription

1 Aldehydes and Ketones Preparation of Aldehydes xidation of Primary Alcohols P 1o alcohol ydroboration of a Terminal Alkyne, followed by Tautomerization B 3, TF , K 2 terminal alkyne zonolysis of Alkenes aving Vinylic ydrogen Zn/Ac eduction of Acid hlorides --- l + LiAl(tBu) eduction of Esters --- ' + [( 3 ) 2 2 ] 2 Al- 3 + DIBA 1

2 Preparation of Ketones xidation of Secondary Alcohols --- Jones' reagent, or K 2 r 2 7 ' ' 2 o alcohol ydration of an Alkyne, followed by Tautomerization --- gs ' 4, 2 S 4, 2 ' alkyne 2 Terminal alkynes give methyl ketones. zonolysis Zn/Ac ' ' Friedel-rafts Acylation --- l + -Ar All 3 Ar Substituents on ring cannot be meta directors or amino. 2

3 eaction of rganocadmium or rganocuprate ompounds with Acid hlorides 'MgX + dl 2 ' 2 d + 2 MgXl ' = 1o alkyl or aryl ' 2 d l 2 --', but not ', may have -N 2, -N, -- and -. 2 'Li + ux Liu' 2 + LiX Liu' l --' + 'u + Lil Structural Features of Aldehydes and Ketones Both contain the δ+ δ carbonyl group and only carbons or hydrogens ( or ) sp bonded to this group. ( or ) 2 In aldehydes at least one hydrogen is joined to the carbonyl carbon (formaldehyde has two). In ketones, only carbons are bonded to the carbonyl carbon. Since ordinary carbanions and hydride ions are very poor leaving groups, substitution does not usually occur at the carbonyl carbon of aldehydes or ketones. π 3

4 eactions of Aldehydes and Ketones xidation Aldehydes are easily oxidized to carboxylic acids, ketones are not. Aldehydes (Ar) 2 or r 3 or K 2 r 2 7 or KMn 4, etc. (Ar) Tollen's test for aldehydes: + Ag(N 3 ) + 2 (Ar) Fehling's test, Benedict's test: - - (Ar) + Ago (not Ar) + 2 u complexed with citrate or tartarate, in solution + u 2 red precipitate Ketones hot KMn 2 2 ' 4 or hot N 3 Vigorous conditions required for reaction. + 2 ' 2 + ' 4

5 Nucleophilic Additions :Nu or :Nu - is a generic nucleophile. ' Nu - δ+ δ, ' = alkyl, aryl, ' Nu δ δ becoming tetrahedral sp 2 sp 3 ' Nu + Nu ' Since there is an increase in crowding on going from reactant to transition state (~120 o to ~109 o ), some steric effects might be expected. This is one reason aldehydes (less crowded) are more reactive than ketones. 5

6 Nucleophilic additions may be acid catalyzed ' + + ' ' More easily attacked by nucleophile than unprotonated carbonyl. owever, when acid catalysis is employed one should usually be careful to avoid completely converting the nucleophile to its conjugate acid (which would be much less nucleophilic). Acetal (ketal) Formation aldehyde or unhindered ketone an acetal (or ketal) 6

7 Mechanism + an aldehyde or unhindered ketone a hemiacetal (or hemiketal) an acetal (or ketal) - + 7

8 Acetals (ketals) undergo acid hydrolysis to regenerate the carbonyl compound, but are inert to many other reaction conditions (they are a type of ether); therefore they are employed as protecting groups. For example Desired to reduce ketone, but aldehyde is more reactive. ( 2 ) ) NaB 4 2) 3 + 8

9 Addition of Grignard eagents Already extensively discussed: a powerful method for synthesis of alcohols. atalysis by a Bronsted-Lowry acid is not an option. owever, catalysis by certain Lewis acids, Mg +2 for example, is possible. ' + Mg+2 Mg ' ' More easily attacked by nucleophile than uncomplexed carbonyl. Mg Formation of yanohydrins ' + K + - N 3 + ' N 9

10 These compounds can be hydrolyzed by base or acid to give α-hydroxyacids or α,β-unsaturated acids, respectively , K heat N heat - K + l Addition of Derivatives of Ammonia + Kl weak acid + N 2 a primary catalyst amine + N 2 hydroxylamine weak acid catalyst N N an imine an oxime ximes, 2,4-DNPs, and semicarbazones are used as derivatives in identifying aldehydes and ketones. 2 N + N 2 N N 2 weak acid catalyst N N 2 N N 2 a 2,4-dinitrophenylhydrazone 10

11 Mechanism + 2 N G N 2 G N G a carbinolamine 3 + N G N G 2 N G Wittig eaction aldehyde or ketone + Ph 3 P + ' a phosphorous ylide ', ' =, Ar, Ph 3 P 11

12 Preparation of the ylide Ph 3 P + X triphenylphosphine ' X = Br, l, I Ph 3 P ' X a phosphonium salt BuLi or Na Ph 3 P ' ylide Ph 3 P ' Mechanism for eaction of Ylide with arbonyl --- Ph 3 P ' an ylide Ph 3 P ' a betaine Ph 3 P ' Ph 3 P + ' 12

13 annizzaro eaction α hydrogens are hydrogens on an α carbon. An α carbon is one that is attached to the functional group, in this case the = group: concentrated aq. Na 2 or Ar No α hydrogens + - Na + rossed annizzaro eaction Na + + ' concentrated aq. Na + ' No α hydrogens - Na + + ' + but, if formaldehyde is one of the aldehydes it will be oxidized and not reduced No α hydrogens + formaldehyde concentrated aq. Na + - Na + sodium formate 13

14 Mechanism or Ar + No α hydrogens Na + ' hydride transfer Na + ' Na + + ' + Na + This reaction is of more interest mechanistically than synthetically owing to the limitation of no a-hydrogens on the aldehyde. 14

15 onjugate Addition of Nucleophiles to a,b-unsaturated Aldehydes and Ketones --- The carbonyl group activates the p-bond at the b position for nucleophilic attack. :Nu resonance stabilized Note: If Nu is neutral here, it will be + here. Nu + Nu ommon examples of conjugate addition to aldehydes or ketones involve amines, N - [especially from ( 2 5 ) 2 Al-N], and the "" group from a lithium diorganocopper, Li + 2 u -, (a Gilman reagent). 15