2.3- Dimethylsuccinic acid

Into a 500 ml. round-bottomed flask, provided with a double surface condenser, place 50 g. (63 ml.) of pure, dry acetone, 50 g. (47 ml.) of ethyl cvanoacetate (Section 111,131) and 0-5 g. of piperidine. Allow to stand for 60 hours and heat on a water bath for 2 hours. Treat the cold reaction mixture with 100 ml. of ether, wash with dilute hydrochloric acid, then with water, and dry over anhydrous sodium or magnesium sulphate. Distil under diminished pressure and collect the ethyl fcopropylidene cyanoacetate (ethyl a-cyano-pp-dimethylacrylate) at 114 116°/14 mm.(l). The yield is 39 g. 

Dissolve 20 g. of the cyano ester in 100 ml. of rectified spirit and add a solution of 19 2 g. of pure potassium cyanide in 40 ml. of water. Allow to stand for 48 hours, then distil off the alcohol on a water bath. Add a large excess of concentrated hydrochloric acid and heat under reflux for 3 hours. Dilute with water, saturate the solution with ammonium sulphate, and extract with four 75 ml. portions of ether. Dry the combined ethereal extracts with anhydrous sodium or magnesium sulphate, and distil off the ether. Recrystallise the residual acid from excess concentrated hydrochloric acid, and dry in the air. The yield of pure tw-dimethyl-succinic acid, m.p. 141-142°, is 12 g. 

The appropriate succinic acid can be prepared by condensation of the nnsntunitcd cyano ester with alcoholio potassium cyanide. 

A better method involves the interaction of an alkyl bromide and thiourea to form an alkyl ao-thiourea, followed by hydrolysis of the latter with sodium hydroxide solution, for example  

The lower members have remarkably disagreeable odours, but the offensivo odour diminishes with increasing carbon content until it almost disappears at about CioH2i SH, Ji-dodecyl (lauryl) mercaptan. 

Mercaptans (or thio-alcohols or thiols), the sulphur analogues of the alcohols, were formerly prepared by the interaction of an alkyl halide and sodium hydrosulphide in alcoholic solution  

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The preparation of as-dimethylsuccinic acid according to the following scheme has a number of points of interest ... 

Monocrotaline on alkaline hydrolysis yields retronecine and monocrotic acid, CjHijOg, b.p. 145-6°/18 mm., [a]p 0°, which forms a p-bromo-phenacylester, m.p. 78°,and a methyl ester, b.p. 94-6°/18 mm., characterised by a 2 4-dinitrophenylhydrazone, m.p. 95-6° see below). The acid gives the iodoform reaction and is oxidised by sodium hypobromite to a mixture of dl- and mcso-aa -dimethylsuccinic acids (I). These and other reactions show that monocrotic acid is a -dimethyllaevulic acid (II) and this has been eonfirmed by comparison with a synthetic specimen of the acid. The methyl ester of the synthetie acid forms a mixture of 2 4-dinitrophenylhydrazones, m.p. 108-9° and 121-2°, into which the analogous produet, m.p. 95-6°, first made from methyl monocrotate see above), has also been separated. 

The formation of meso-dimethylsuccinic acid from dimethylmaleic acid and the racemic mixture from dimethylfumaric acid implies that both hydrogen atoms add to the same side of the unsaturated molecule 11). Bourguel (12) also noted that disubstituted acetylenes yielded initially cis-ethylenes but that trans isomers were formed if the hydrogenations were protracted. 

Dimethylsuccinic acid [597-43-3] M 146.1, m 141°. Crystd from EtOH/ether or EtOH/chloroform. 

Dimethylpyrazole, 842 2 5-Dimethyl pyrrole, 839 Dimethyl sebacate, 938, 939,940 aa-Dimethylsuccinic acid, 490, 495 Dimethyl sulphate, 303... 

The dimethyl derivative, Compound 27, was prepared from racemic 1,2 dimethylsuccinic acid by first resolving with quinine (14, 15, 16), preparing the dimethyl ester, and then proceeding exactly by the same sequence used for DIOP from dimethyl tartrate (7). Table VI gives melting points and rotations of the compounds in Table III. 

The synthesis of 2,2-dimethylsuccinic acid (Expt 5.135) provides a further variant of the synthetic utility of the Knoevenagel-Michael reaction sequence. Ketones (e.g. acetone) do not readily undergo Knoevenagel reactions with malonic esters, but will condense readily in the presence of secondary amines with the more reactive ethyl cyanoacetate to give an a, /f-unsaturated cyanoester (e.g. 15). When treated with ethanolic potassium cyanide the cyanoester (15) undergoes addition of cyanide ion in the Michael manner to give a dicyanoester (16) which on hydrolysis and decarboxylation affords 2,2-dimethylsuccinic acid. 

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