Malonic acid, substituted bromination

When it is required to prepare an a-bromo acid from a carboxylic acid which is not particularly readily available commercially, but which can be synthesised by the malonic acid route (Section 5.11.6, p. 680), advantage may be taken of the ease of bromination in the a-position of the intermediate alkylmalonic acid. The substituted bromomalonic acid undergoes ready decarboxylation on heating to yield the a-bromo acid (e.g. 2-bromo-3-methylpentanoic acid, Expt 5.166). 

The heart of the preparation of capsaicin is a malonic ester synthesis. The first step is bromination of the primary alcohol by phosphorous tribromide. The resulting primary alkyl bromide is used to alkylate the sodium salt of diethyl malonate. A substituted malonic acid derivative is obtained following basic hydrolysis of the ester groups. 

As part of a project to synthesize stable analogs of the indole-2,3-quinodimethane system, the 2,4-di-hydropyrrolo[3,4]indole (251) has been prepared from formylindole (249). Knoevenagel condensation with ethyl malonate followed by bromination and nucleophilic substitution of the bromide with azide yields (250), which immediately undergoes intramolecular 1,3-dipolar cycloaddition to give the triazoline (252). Treatment of (252) with toluene-p-sulfonic acid affords diethyl diazomalonate and (251 ... 

The problem in the synthesis of malonic acid is to replace a hydrogen atom in acetic acid by the carboxyl group. This is accomplished in the same way as that by which methane is converted into acetic acid. One hydrogen atom is first replaced by a halogen atom, by treating acetic acid with chlorine or bromine. The substituted acid is then heated with potassium cyanide, and the cyanoacetic acid so formed is hydrolyzed by boiling with a solution of an alkali. The changes are indicated by the formulas,—... 

Adolf Pinner (1842-1909), Professor of Chemistry at the Veterinary Institute in Berlin, elucidated the structure of nicotine in 1893 by oxidative degradation with bromine. [528] In addition to nicotinic acid, he also found methylamine and malonic acid. With the knowledge ofthe overall chemical formula, and the fact that nicotine had to contain two tertiary amine functions, he postulated it as a 3-substituted pyridine linked to a 2-substituted N-methylpyrrolidine. 

Campaigne et al. have used 3-thenyl bromide obtained by benzoyl peroxide-catalyzed, side-chain bromination of 3-methylthiophene with A -bromosuccinimide, as a starting material for 3-substituted thiophenes. - 22 3-Methylthiophene is now prepared commercially from itaconic acid. The reactive halogen in 3-thenyl bromide could be directly reacted with a variety of nucleophiles, such as cyanide, or malonate, to give more complex 3-substituted compounds. 3-Thenyl bromide was converted by the Sommelet reaction to 3-thio-phenealdehyde which, with silver oxide, was oxidized to 3-thio-... 

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