Methyl Bromoacetate

(1; R = Me)

[96-32-2]  · C3H5BrO2  · Methyl Bromoacetate  · (MW 152.98) (2; R = Et)

[105-36-2]  · C4H7BrO2  · Ethyl Bromoacetate  · (MW 167.01)

(forms a variety of enolates; the bromine atom is readily substituted by nucleophiles; undergoes carbonyl substitution reactions)

Physical Data: (1) bp 51-52 °C/15 mmHg; d 1.616 g cm-3; n20D 1.4580. (2) bp 58-59 °C/15 mmHg; d 1.506 g cm-3; n20D 1.4489.

Solubility: sol common organic solvents.

Form Supplied in: colorless liquid; widely available.

Purification: vacuum distillation; decomposes upon distillation at atmospheric pressure.

Handling, Storage, and Precautions: corrosive lachrymator, irritating to eyes and respiratory system; should be used only in a chemical fume hood.

Formation of Enolates.

The reagent reacts with zinc metal to produce a zinc enolate (3) (eq 1) which is usually trapped in situ by aldehydes or ketones to produce b-hydroxy esters (the Reformatsky reaction).1 Similar redox reactions to form enolates occur with a variety of metals.1a

Proton removal with alkoxide bases forms a-bromo ester enolates (4) (eq 2), which are trapped in situ by aldehydes or ketones to produce glycidic esters (the Darzens condensation).2 The use of Lithium Dicyclohexylamide gives excellent yields.3 Enolates analogous to (4) (M = Li) are produced with Lithium Hexamethyldisilazide.4

Nucleophilic Substitution.

The bromine in methyl bromoacetate is readily substituted by nucleophiles. Substitution with Triphenylphosphine5 or with trialkyl phosphites6 produces reagents used for Wittig alkenation reactions. Similar alkenation reagents are obtained with Tri-n-butylstibine (eq 3),7 Dibutyl Telluride (eq 4),8 and tributylarsine.9 A wide variety of carbon nucleophiles are alkylated by methyl bromoacetate including ketone10 and ester enolates,11 metallo imines,12 hydrazones,13 oximes,14 and metal p-allyls.15

Carbonyl Substitution.

Reaction of methyl bromoacetate with lithium perfluoroalkyls gives good yields of ketones (eq 5), presumably as a result of the stability of the intermediate hemiacetal anion (5).16 Transesterification of methyl bromoacetate can be achieved efficiently with a distannoxane catalyst (eq 6).17

Related Reagents.

Chloroacetonitrile; Methyl Chloroacetate.

1. (a) Rathke, M. W.; Weipert, P. COS 1991, 2, 277. (b) Rathke, M. W. OR 1975, 22, 423.
2. (a) Newman, M. S.; Magerlein, B. J. OR 1949, 5, 413. (b) Rosen, T. COS 1991, 2, 409.
3. Taguchi, H.; Yamamoto, H.; Nozaki, H. JACS 1974, 96, 3010.
4. Borch, R. F.; TL 1972, 3761.
5. Maercker, A. OR 1965, 14, 270.
6. Wadsworth, Jr. W. S. OR 1977, 25, 73.
7. Huang, Y.; Shen, Y.; Chen, C. TL 1986, 27, 2903.
8. Huang, X.; Xie, L.; Wu, H. JOC 1988, 53, 4862.
9. Shi, L.; Wang, W.; Wang, Y.; Huang, Y.-Z. JOC 1989, 54, 2027.
10. Lal, K.; Salomon, R. G. JOC 1989, 54, 2628.
11. Petragnani, N.; Yonashiro, M. S 1980, 710.
12. Kieczykowski, G. R.; Schlessinger, R. H.; Sulsky, R. B. TL 1976, 597.
13. Enders, D.; Bockstiegel, B. S 1989, 493.
14. Hiroi, K.; Otsuka, M.; Sato, S. CL 1985, 1907.
15. Trost, B. M.; Weber, L.; Strege, P. E.; Fullerton, T. J.; Dietsche, T. J. JACS 1978, 100, 3416.
16. Uno, H.; Shiraishi, Y.; Suzuki, H. BCJ 1989, 62, 2636.
17. Otera, J.; Yano, T.; Kawabata, A.; Nozaki, H. TL 1986, 27, 2383.

Michael Rathke & Robert Elghanian

Michigan State University, East Lansing, MI, USA

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