5-bromopentane carboxylic acid

Strategy The malonic ester synthesis converts an alkyl halide into a carboxylic acid having two more carbons. Thus, a seven-carbon acid chain must be derived from the five-carbon alkyl halide 1-bromopentane. 

The retrosynthetic analysis shown for 220 allows the total synthesis. Catalytic hydrogenation of223 gives 1-pentene (see Chapter 19, Section 19.3.2), which reacts with HBr to give 2-bromopentane (Chapter 10, Section 10.2). The reaction of 2-bromopentane and magnesium metal, followed by reaction with carbon dioxide and aqueous hydrolysis, leads to the requisite carboxylic acid. Reaction of the carboxylic acid with thionyl chloride leads to the acid chloride, which reacts with dimethylamine to give 222. 

Cyclopropane-1,1-dicarboxylic acid (30a) reacted with hydrobromic acid to (2-bro-moethyl)malonic acid (31a) . In a similar reaction, ethyl 1-acetylcyclopropane-l-carboxylate (31b) ( C enriched) was converted to 5-bromopentan-2-one upon treatment with hydrobromic acid and decarboxylation." In 2-benzoyl-3-phenylcyclopropane-1,1-dicarboxylic acid (31c), two different activating functions are present and can influence the addition of hydrogen bromide. In fact, products arising from the cleavage of either bond that link the phenyl-substituted carbon were isolated. Both primary products had lost hydrogen bromide and carbon dioxide. 

The acetic acid portion, which includes the methylene group and the carboxyl group, is derived from a malonate ester. The alkyl group is available as a haloalkane such as 3-bromopentane. 

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