1,1-Dicarboxylic acids, decarboxylation from acid salts

Practically all pyridazine-carboxylic and -polycarboxylic acids undergo decarboxylation when heated above 200 °C. As the corresponding products are usually isolated in high yields, decarboxylation is frequently used as the best synthetic route for many pyridazine and pyridazinone derivatives. For example, pyridazine-3-carboxylic acid eliminates carbon dioxide when heated at reduced pressure to give pyridazine in almost quantitative yield, but pyridazine is obtained in poor yield from pyridazine-4-carboxylic acid. Decarboxylation is usually carried out in acid solution, or by heating dry silver salts, while organic bases such as aniline, dimethylaniline and quinoline are used as catalysts for monodecarboxylation of pyridazine-4,5-dicarboxylic acids. 

Very little work has been done on fluoro derivatives of thiophenes. 2-Fluorothiophene was obtained in low yield from treatment of 2-iodothiophene with arsenic trifluoride. The action of fluoroboric acid on thiophenediazonium salts was unsuccessful. It may be useful for the preparation of 4-, 5-, 6- or 7-fluorobenzo[6]thiophenes from the appropriate amines. However, these are more conveniently prepared from fluorine-substituted benzenethiols by ring-closure reactions. For example 4,5,6,7-tetrafluorobenzo[6 Jthiophene was obtained by decarboxylation of the corresponding 2,3-dicarboxylic acid (equation 99) prepared by condensation of pentafluorobenzenethiol with diethyl acetylenedicarboxylate (Section 3.15.3.4.1). 2-Fluorothiophene has been prepared from 2-thienyllithium using perchloryl fluoride, and 2-fluorobenzo[ Jthiophene from the 2-lithio derivative in a similar manner (Section 3.14.3.9.1). 

Ravdin and Crandall (695) isolated a protein fraction from rat liver which converted homogentisic acid to a jS-keto acid decarboxylated slowly by aniline citrate at 38°C. A second enzyme fraction was obtained which converted this keto acid to acetoacetic acid. The /3-keto acid was isolated as its silver salt and was found also to be a dicarboxylic acid and a /3-diketone, and to give fumaric and acetoacetic acids on hydrolysis. The proposed formulation as fumarylacetoacetic acid (see diagram 8) has since beeri amply confirmed. Conversion of homogentisic acid to fumarylacetoacetic acid by a liver preparation involves uptake of the expected two atoms of oxygen (e.g., 489, 523). 

A number of a-nitro carboxylic acids are easily dicarboxylated to furnish nitro compounds. The synthesis of nitromethane in this manner is a classical example (38%). Nitroethane and higher homologs have been similarly prepared from the a-bromo acids and sodium nitrite. Another example is found in the synthesis of phenylnitromethane. Treatment of benzyl cyanide with methyl nitrate in the presence of sodium ethoxide gives the sodium salt of the aci-niao compound, which is then hydrolyzed and decarboxylated. ... 

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