Ethyl Dibromoacetate


[617-33-4]  · C4H6Br2O2  · Ethyl Dibromoacetate  · (MW 245.90)

(used in preparation of a-bromo and a,a-dialkyl substituted esters;1 undergoes Reformatsky/Darzens reactions with aldehydes and ketones2)

Physical Data: bp 194 °C; 77 °C/12 mmHg; d 1.9025 g cm-3.

Solubility: insol H2O; sol hexane, ether, CH2Cl2, acetone, EtOAc, EtOH.

Form Supplied in: colorless to light yellow liquid; practical grade commercially available.

Handling, Storage, and Precautions: lachrymator; avoid inhalation of fumes. Handle in a fume hood.

Alkylation of Br2CHCO2Et with organoboranes in the presence of Potassium t-Butoxide or a hindered phenoxide base affords a-bromo esters or a,a-dialkyl substituted esters, depending upon the amounts of reagents employed and the reaction temperature (eq 1).1 The phenoxide base (pK 11.7) minimizes self-condensation of both the starting material and the product. The procedure in eq 1 represents an attractive alternative to the classical malonic ester synthesis.3

Reformatsky-type addition of Br2CHCO2Et to aldehydes or ketones at low temperature in the presence of zinc/silver-graphite provides a-bromo-b-hydroxy esters in excellent yield (eq 2).2 Mild base treatment then yields the expected glycidic esters, while other transformations of the initial adduct have also been reported (eq 2).4 The use of Zn/Ag-graphite represents a major improvement over the classical Reformatsky conditions,5 which required the use of Zn, Mg, or Ca amalgams with Br2CHCO2Et to avoid reductive loss of the bromo substituent.5 The Zn/Ag-C reagent has also been utilized with aldonolactones.6 Modification of the Reformatsky-type zinc reagent by the addition of Diethylaluminum Chloride allows the isolation of a,b-unsaturated esters in moderate yield (eq 3),7 an alternative to the Wadsworth-Emmons reaction.8

The Triethylborane catalyzed radical addition of Br2CHCO2Et to ketene acetals affords unsaturated 1,4-diesters in fair yield (eq 4),9 although the generality of the reaction has not been explored.

Under precisely controlled conditions (all reagents dispersed on sand), benzenethiolate displacement on Br2CHCO2Et provides the corresponding thioacetal (eq 5).10 Further alkylation should provide a route to pyruvic acid derivatives.

The ethoxycarbonylcyclopropanation of both simple alkenes (eq 6)11 and alkylidenemalonates (eq 7)12 with Br2CHCO2Et in the presence of copper powder or zinc has also been reported.

Related Reagents.

Dichloroacetonitrile; Methyl Dichloroacetate.

1. (a) Brown, H. C.; Rogic, M. M.; Rathke, M. W.; Kabalka, G. W. JACS 1968, 90, 1911. (b) Brown, H. C.; Nambu, H.; Rogic, M. M. JACS 1969, 91, 6855.
2. Furstner, A. JOM 1987, 336, C33.
3. House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972; pp 510-518, 756-761.
4. Darzens, G. CR 1936, 203, 1374.
5. (a) Miller, R. E.; Nord, F. F. JOC 1951, 16, 728. (b) Furstner, A. S 1989, 571.
6. Csuk, R.; Glanzer, B. I. J. Carbohydr. Chem. 1990, 9, 797.
7. Takai, K.; Hotta, Y.; Oshima, K.; Nozaki, H. BCJ 1980, 53, 1698.
8. Wadsworth, Jr., W. S.; Emmons, W. D. OSC 1973, 5, 547.
9. Sugimoto, J.; Miura, K.; Oshima, K.; Utimoto, K. CL 1991, 1319.
10. Bram, G.; Loupy, A.; Roux-Schmitt, M. C.; Sansoulet, J.; Strzalko, T.; Seyden-Penne, J. S 1987, 56.
11. Kawabata, N.; Kamemura, I.; Naka, M. JACS 1979, 101, 2139.
12. Gaudemar-Bardone, F.; Gaudemar, M. CR(C) 1972, 274, 991.

Gordon L. Bundy

The Upjohn Company, Kalamazoo, MI, USA

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