Ethyl Mandelate

(±)-(R = Et)

[4358-88-7]  · C10H12O3  · Ethyl Mandelate  · (MW 180.22) (R)-(-)

[10606-72-1] (S)-(+)

[13704-09-1] (±)-(R = Me)

[4358-87-6]  · C9H10O3  · Methyl Mandelate  · (MW 166.19) (R)-(-)

[20698-91-3] (S)-(+)


(precursor of tertiary a-hydroxy acids;1 optically active starting material;2,3 chiral derivatizing agent4)

Physical Data: R = Et, mp 37 °C; specific rotations reported for the optically active forms are -128.4° (c = 6.7, CHCl3, 20 °C), +134° (c = 3, CHCl3, 21 °C). R = Me, mp 58 °C; specific rotations reported for the optically active forms are -214° (CS2, 18 °C), +144° (c = 1, MeOH, 20 °C).

Preparative Methods: simple esters of mandelic acid are commercially available in racemic and both optically active forms. Other esters are accessible by acid-catalyzed esterification or esterification of Mandelic Acid using 1,3-Dicyclohexylcarbodiimide or an acid chloride of an O-protected mandelic acid intermediate.4,5

Mandelic acid esters can be doubly deprotonated by 2 equiv of Lithium Diisopropylamide to generate enediolates that react readily with primary or secondary alkyl halides to yield tertiary hydroxy acid derivatives (eq 1).1 The use of chiral directing groups instead of the ethyl group of ethyl mandelate makes this method useful as an asymmetric synthesis. The alkylation chemistry in eq 1 using enediolate intermediates also leads to carbon alkylation at the benzylic carbon in reactions with sp2-hybridized electrophiles (aldehydes, ketones, aldimines) and has been used in asymmetric synthesis of a b-lactam using menthyl mandelate and benzaldehyde N-phenylimine.6

Mandelic acid esters are also useful chiral auxiliaries because both enantiomers are commercially available and inexpensive. For example, they serve as useful chiral auxiliaries in Diels-Alder reactions (de >95%) (eq 2)3 and as precursors for chiral acetals.7

Optically active mandelic acid esters are also useful as derivatizing agents for NMR analyses of the enantiomeric purity of isotopically substituted carboxylic acids, alcohols, and amines through analysis of the corresponding derivatives using either the carboxyl group or the hydroxy group.4

Related Reagents.

Dilithioacetate; Ethyl Bromozincacetate; Ethyl Lithioacetate; Lithium Diisopropylamide; Methyl O-Methyllactate; Phenoxyacetic Acid.

1. Ciochetto, L. J.; Bergbreiter, D. E.; Newcomb, M. JOC 1977, 42, 2948.
2. Furuta, K.; Hayashi, S.; Miwa, Y.; Yamamoto, H. TL 1987, 28, 5841.
3. Charlton, J. L.; Koh, K. SL 1990, 333.
4. Parker, D. JCS(P2) 1983, 88.
5. Thayer, F. K. OSC 1948, 1, 12.
6. Gluchowski, C.; Cooper, L.; Bergbreiter, D. E.; Newcomb, M. JOC 1980, 45, 3413.
7. Mash, E. A.; Arterburn, J. B.; Fryling, J. A.; Mitchell, S. H. JOC 1991, 56, 1088.

David E. Bergbreiter

Texas A & M University, College Station, TX, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.