[66131-14-4]  · C6H6Br2O4  · 5,5-Dibromo-2,2-dimethyl-1,3-dioxane-4,6-dione  · (MW 301.92)

(selective a-bromination of aldehydes1 and a-bromination of a,b-unsaturated ketones;1 reductive coupling to an ethylenetetracarboxylate3,4)

Physical Data: mp 75-76 °C.

Solubility: sol diethyl ether, carbon tetrachloride, and most other organic solvents.

Form Supplied in: white solid.

Analysis of Reagent Purity: 1H NMR; elemental analysis (Br).

Preparative Methods: by bromination of Meldrum's acid (2,2-Dimethyl-1,3-dioxane-4,6-dione)2 (commercially available) with Bromine in the presence of Potassium Hydroxide or Sodium Hydroxide eq 1).3

Purification: recrystallization from CCl4.

Handling, Storage, and Precautions: can be stored for months at 0 °C.

Bromination of Aldehydes and Ketones.

This brominating reagent is especially useful for the synthesis of a-monobromoaldehydes1 and the preparation of a-brominated a,b-unsaturated ketones.1 The bromination is usually carried out by stirring an ether solution of the reagent and the carbonyl compound (1:2 ratio) at rt. The bromination product is easily isolated by extracting the Meldrum's acid byproduct into aqueous sodium hydrogen carbonate. Heptanal is thus cleanly a-monobrominated (eq 2),1 as are aldehydes having a methine at the a-position such as isobutanal and cyclohexanecarbaldehyde. Methyl ketones with no a-hydrogens, such as acetophenone, are smoothly monobrominated as well.1 However, the regioselectivity in the bromination of unsymmetrical ketones, e.g. 2-methylcyclohexanone and 4-methyl-2-pentanone, is not good, and this is not a synthetically useful process (eq 3).1

5,5-Dibromo-2,2-dimethyl-1,3-dioxane-4,6-dione selectively monobrominates a,b-unsaturated ketones at the a-position without side reactions, such as addition to the double bond or allylic bromination (eq 4).1 In the case of ketones which enolize with difficulty, it is advantageous to enhance the rate of the reaction by the addition of catalytic amounts of Hydrogen Bromide or by heating to reflux. Representative selective brominations of some a,b-unsaturated ketones are presented in eqs 4-7.1 In contrast, the bromination of 3-methyl-2-cyclopenten-1-one with this reagent in CCl4 under reflux gave no selectivity, resulting in 18% 5-bromo-, 11% 4-bromo-, 2% 5,5-dibromo- and 2% 4,5-dibromo-3-methyl-2-cyclopenten-1-one.4

Synthesis of Ethylenetetracarboxylate.

Reductive coupling of 5,5-dibromo-2,2-dimethyl-1,3-dioxane-4,6-dione takes place spontaneously in DMF at rt to afford diisopropylidene ethylenetetracarboxylate (eq 8).3 It was subsequently reported that repeated attempts to prepare this diisopropylidene ethylenetetracarboxylate according to this procedure gave erratic results, and that more reliable results and improved yields could be obtained by adding 5-bromo-2,2-dimethyl-1,3-dioxane-4,6-dione to a solution of 1 equiv of 5,5-dibromo-2,2-dimethyl-1,3-dioxane-4,6-dione in dry DMF which had been standing for 1 week in a well-illuminated place.5 Dissolution of the 5-bromo derivative was quickly followed by the precipitation of the required ethylenetetracarboxylate in 57% yield (mp 230 °C, dec.) (eq 9).5 This dimeric compound was used as a precursor to tricarbon monoxide via pyrolytic decomposition (eq 10).6

Synthesis of Isocyanoamines.

5,5-Dibromo-2,2-dimethyl-1,3-dioxane-4,6-dione reacts with N,N-disubstituted hydrazines to produce hydrazone derivatives, which serve as starting materials for dialkylisocyanoamines upon pyrolysis (eq 11).7

1. Bloch, R. S 1978, 140.
2. Davidson, D.; Bernhard, S. A. JACS 1948, 70, 3426.
3. Synder, H. R.; Kruse, C. W. JACS 1958, 80, 1942.
4. Novikov, V. L.; Shestak, O. P.; Kamernitskii, A. V.; Elyakov, G. B. Izv. Akad. Nauk SSSR, Ser. Khim. 1982, 476 (CA 1982, 96, 180 832).
5. Brown, R. D.; Godfrey, P. D.; Elmes, P. S.; Rodler, M.; Tack, L. M. JACS 1985, 107, 4112.
6. Brown, R. D.; Eastwood, F. W.; Elmes, P. S.; Godfrey, P. D. JACS 1983, 105, 6496.
7. Briehl, H.; Lukosch, A.; Wentrup, C. JOC 1984, 49, 2772.

Norbert De Kimpe

University of Gent, Belgium

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