Sodium methylsuccinate

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

This H-transfer reduction with sodium formate and employing catalysis by a water-soluble rhodium-phosphine catalyst yields dimethyl methylsuccinate [117]. 

Disodium methylsuccinate was made by hydrogenating a concentrated solution of itaconic acid supplied by Chas. Pfizer and Company in aqueous sodium hydroxide (pH. 8.7) over Raney nickel catalyst at 50 p.s.i. and 80-100°. After the catalyst was removed by filtration, the product was isolated by evaporation of the water and the residue was dried in a vacuum oven at 70-80°. 

Alternative methods of preparing the starting acids can be used, but are generally less convenient. Benzo[6 ]thiophene derivatives were prepared from 2-methyl-3-(2 -thenoyl)propionic acid, which was obtained either by reacting 2-thienylmagnesium iodide with methylsuccinic anhydride, or by coupling 2-bromoacetylthiophene with the sodium salt of diethyl methylmalonate (45JA1645). 

The asymmetric center of 120b can be inverted with carbon nucleophiles, as demonstrated by the synthesis of 1-ethyl ( S)-( — )-2-methylsuccinate (145) [52]. The reaction of 120b with sodium di- r -butylmalonate gives triester 144 with total inversion of configuration. Hydrolysis and decarboxylation furnishes the monoacid 145 (99% ee) in 54% overall yield from ethyl L-lactate. 

Reactions of Thiophen Aldehydes and Ketones.— The Stobbe condensation of some thienylcarbonyl compounds with dimethyl methylsuccinate in the presence of potassium t-butoxide or sodium hydride gave predominantly the ( -half esters of (156), while condensation with dimethyl homophthalate gave predominantly the (Z)-half ester of (157). Thiophen-2-aldehydes were shown to add smoothly to a -unsaturated ketones and nitriles, under the catalytic influence of cyanides, to form (158) and (159), respectively. Thiophen-2-aldehydes have been condensed with aliphatic amines and phenylenediamine to give Schiff bases ... 

---