Chapter 17 Aldehydes and Ketones

Transcription

1 hapter 17 Aldehydes and Ketones arbonyl Groups polarized (1) Aldehydes and Ketones ' aldehydes ketones : and : are poor leaving groups (2) arboxylic Acid Derivatives l ' ' 2 carboxylic acid substituent could be a leaving group (, l,, 2 ); provides for similar reactivity as aldehydes and ketones but sometimes different reactivity; we saw a glimpse of this difference already

2 1) LiAl 4, Et 2 2) 2 3 1) LiAl 4, Et 2 2) 2 LiAl 4 2 LiAl 4 3 omenclature: prefix - parent - suffix (1) Aldehydes: need the longest chain that contains the () group

3 3 butanal ,4-dimethylpentanal hydroxy-4-methylhexanal 3 (2) Ketones: -one as suffix propanone (acetone) chloro-5-hydroxy-3-hexanone l There are a number of common carbonyl groups: 3

4 Synthesis of Aldehydes (1) From alcohols (oxidation) P 2 l 2 P 2 l 2 (2) From alkenes (oxidation) 1) 3, 2 l 2 2) Zn, Ac 3 Ac

5 (3) From alkynes disiamylborane B 1) 2), (4) From esters via partial reduction ' 1) DIBA, toluene 2) 3 + ( 3 ) 2 2 Al 2 ( 3 ) 2 3 1) LiAl 4, Et 2 2) 2 LiAl 4 2 LiAl 4 3

6 Synthesis of Ketones (1) xidation of alcohols Jones' reagent P 2 l 2 (2) zonolysis of alkenes (oxidation): can also use KMn 4 with acid ) 3, 2 l 2 2) Zn, Ac (3) ydration (addition of 2 ) to terminal alkynes 2, 2 S 4 gs 4 3 (4) Friedel-rafts Acylation l All 3

7 (5) rgano-opper (uprate) oupling l 1) ( 3 ) 2 uli, Et 2 2) 2 xidation of Aldehydes and Ketones r 3, 2 S 4 2, acetone 3 r 3, 2 S 4 2, acetone ne can also use the Tollens reagent (Ag 2, 4 ) to oxidize aldehydes, and it is a very gentle method for the selective oxidation of aldehydes xidation of aldehyde () takes place via the hydrate 2 r 3 3 +

8 ucleophilic Addition eactions u δ + δ u is sp 2 is sp 3 --' ~ ' ~ 109 What about the nucleophile? (1) ucleophile can be (2) ucleophile can be (3) Steric effects when nucleophile adds to carbonyl carbon Which is more reactive: aldehydes or ketones? Aldehydes (): (i) nucleophile can easily approach carbonyl carbon (ii) addition product is less sterically hindered (iii) transition state is less crowded: low G (iv) greatest polarization of the = bond with being most δ+ since cannot stabilize the positive charge on carbon very well Ketones (() ): (i) groups can stabilize the partial positive charge on the carbonyl carbon

9 Let us consider a simple nucleophile such as 2 2 ' ' hydrate (gem diol) geminal = "same carbon" an equilibrium: position of equilibrium depends on and (on stability of aldehyde and ketone vs the hydrate product) K eq l 2 l 3 l 2 l 2 F 3 F 3 (1) addition of water is more favorable for aldehydes than for ketones (2) electronegative groups attached to carbonyl carbon make addition more favorable δ δ + Why is this useful? The more a compound favors addition at equilibrium, the more rapidly it will react in addition reactions -- the transition state has similar preferences as the addition intermediate (ammond postulate again...)

10 transition state E n erg y G G G rxn eaction oordinate The equilibrium can be established with either base or acid catalysis: Base: δ δ + + Acid: (a) If nucleophile is strong enough, there is (b) If nucleophile is not strong enough, need to by coordination to a Bronsted acid (+) or a Lewis acid

11 addition (1) is a weak acid pk a ~ 9.1 (not much at equilibrium) (2) δ δ + + catalyzed by base (in order to make ) or by direct addition of heat ( ) 1) LiAl 4, TF 2) Grignard addition δ Mg X δ + Et 2 so not an equilibrium magnesium coordinates carbonyl oxygen (Mg is Lewis acidic) and makes carbonyl carbon even more electrophilic -- magnesium helps to activate the carbonyl carbon

12 ydride Addition: reduce aldehydes and ketones to alcohols are sources of : and both reagents can 1) ab 4, Et 2) 3 + not reversible so not an equilibrium Amines: nucleophiles with attached hydrogens (good nucleophiles) 2 primary amines secondary amines ' 2 ' ' 2 '

13 (1) Primary Amines (product is an imine): p of the reaction is very important (best at about p = 4.5) δ δ imine protonation to yield a good leaving group

14 all are - 2 for formation of

15 (a) all are equilibria (b) equilibrium favored to reactants for imine so need to (c) oximes, semicarbazones, and hydrazones are (reaction can even be done in 2!) (2) Secondary amines 2 : enamines there is no proton to lose on when you start with a secondary amine ( 2 )

16 3 3 ( 3 ) 2 3 ( 3 ) 2 3 3

17 Wolff-Kishner eaction ' ' ' ' ' ' ' 1) 2 2, K 2) 3 +

18 Acetal Formation + ' acid ' " " 2 " (1) equilibrium so: (a) lots of - and also remove 2 then favor equilibrium to the (b) lots of 2 then favor equilibrium to the (2) protection of ketone? 3 for ester reduction: LiAl 4 is needed but ketone would be reduced at the same time so need to protect (mask, hide) the ketone group ) LiAl 4, Et 2 2) , +

19 Equilibrium: G = T S = Acetal formation has an unfavorable entropy (3 moles <=> 2 moles), so use diol ) Mg, Et ) 3 Br Br Br 3 3 ow? (a) hemiacetal formation: acidic or basic conditions are fine ' 3 + ' 3 ' 3 3 ' 3 ' 3 ' 3 3 ' 3

20 (b) hemiacetal conversion to acetal works in ' ' 3 3 ' 3 ' 3 3 ' 3 acetal 3 ' 3 3 Thioacetals ' S + S aney i 2, Et ' same mechanism as for acetal formation 3 S S S S + 3 aney i 2, Et 3

21 Wittig eaction 2 P ylid Ph Ph Ph Ph = + P Ph Ph Ph triphenylphosphine oxide Ph 3 P 3 Br Ph 3 P 3 a Et 2 Ph 3 P 2 acidic hydrogens PPh 3 2 P Ph Ph Ph betaine PPh 3 oxaphosphatane P + Ph Ph Ph 2 1) Ph 3 P 2 TF 2) 2 + Ph 3 P= 2 1) Ph 3 P 2 TF 2) 2 + Ph 3 P=

22 annizzaro eaction: + + (a) : as a leaving group (b) reaction is driven by the formation of stable carboxylate anion (irreversible) Similar action as ADP in biology: 2 2 ' not aromatic some aromatic character

23 1,2-Addition to arbonyl Group: 2 + u 1 u 2 u addition of u and to 1 and 2 1,4-Addition to α,β-unsaturated Enone: u 2 1 (a) final step is a u u (b) overall reaction is addition of u- to 1 and 4 of enone u (c) need the carbonyl group (=) to have 1,4-addition to the = double bond 1) u 2) 2 no reaction 1) u 2) 2 u What kinds of nucleophiles work?

24 (1) Amines 3 Et 2 Et 3 Et Et 3 (2) addition 1) Et 2 Al-, toluene 2) 3 + agata reaction (3) rgano-copper (uprate) eactions 1) 2 uli 2) 3 +

25 ow to make 2 uli? -X 2 Li pentane -Li + Li-X ui 2 -Li 2 uli + LiI Et 2 1) ( 3 ) 2 uli 2) 3 + 1) ) ) uli 2 3 2) ) 3 MgBr, Et 2 2) ) 3 Li, Et 2 2) 2 1) ( 3 ) 2 uli, Et 2 2) 3 + 3