Methyl, alcohol malonic acid

Methyl Malonate.—This ester is an artificially prepared body, having a fruity odour, somewhat similar to the above-described esters of the fatty acids. It has the formula CH2(C02CHg)2, and boils at 181°. It may be prepared by treating potassium cyan-acetate with methyl alcohol and hydrochloric acid. On saponification with alcoholic potash it yields malonic acid, which melts at 132°, and serves well for the identification of the ester. 

This ester (70 g) and diethyl carbonate (250 mg) were stirred at 90°C to 100°C while a solution of sodium ethoxide [from sodium (7.8 g) and ethanol (1 54 ml)] was added over 1 hr. During addition, ethanol was allowed to distill and after addition distillation was continued until the column heat temperature reached 124°C. After cooling the solution to 90°C, dimethyl sulfate (33 ml) was followed by a further 85 ml of diethyl carbonate. This solution was stirred and refluxed for 1 hr and then, when Ice cool, was diluted with water and acetic acid (10 ml). The malonate was isolated in ether and fractionally distilled to yield a fraction boiling at 148°C to 153°C/0.075 mm, identified as the alpha-methyl malonate. This was hydrolyzed by refluxing for 1 hr at 2.5N sodium hydroxide (350 ml) and alcohol (175 ml), excess alcohol was distilled and the residual suspension of sodium salt was acidified with hydrochloric acid to give a precipitate of the alpha-methyl malonic acid. This was decarboxylated by heating at 180°C to 200°Cfor 30 minutes and recrystallized from petroleum ether (BP 80°C to 100°C) to give 2-(2-fluoro-4-biphenylyl)propionic acid, MP 110°C to 111°C. 

The synthesis of 6a-methyldigitoxigenin acetate (394) has been reported according to Scheme 19.198 Pregn-4-en-21-ol-3,20-dione was converted into its 6a-methyl derivative (387) using a previously described five-step reaction sequence biological hydroxylation furnished the 14a,12-diol (388) and reduction of the derived 21-acetate gave the 5/3-dihydro-steroid (389). Dehydration furnished the A14-olefin (390) which was converted into the 21-mesylate and thence into the lactone (391) by reaction with the monoethyl ester of malonic acid. The crude lactone was decarbox-ylated, reduced to the 3/3-alcohol (392), and converted into the bromohydrin (393) via its 3/3-acetate and thence by debromination into 6a-methyldigitoxigen 3-acetate... 

Malonic Acid.—Using the free acid, under the same conditions as oxalic acid, only results in traces of a red compound being formed, whilst ethyl inalonate in methyl alcohol apparently yields tnalon-o-phenyleneamide-i-arsinie add. 

The synthesis of bixin (533) requires the regiospecific introduction of a Z double bond. Attention was first focused on the total synthesis of (all- )-methylbixin (534) [35]. (3-Methylepichlorohydrin (180) was treated with sodium acetylide (68) to give the alcohol 181 which was transformed with dihydropyran and phosphorus oxychloride to the acetylenic compound 182. Condensation of two moles of 182 with oct-4-ene-2,7-dione (5) in the presence of PhLi resulted in the C2o-diol 183. Treatment with p-toluenesulphonic acid first in toluene gave the diether 184 and afterwards in ethanol led to the diol 185, which was oxidized with Mn02 to the dial 186. The Knoevenagel condensation with malonic acid (187) and methylation with diazomethane gave the diester 188, which was hydrogenated in the presence of Lindlar catalyst and isomerized with iodine to (all- )-methylbixin (534) in an overall yield of 0.04% referred to 180 (Scheme 41). 

The rate of polymerization varied directly with the dimethylsulfoxide concentration and was proportional to the square of the monomer and independent of the oxidant. They also investigated the polymerization of methyl methacrylate with Mn and reducing agents such as dimethyl sulfoxide, diacetone alcohol, and malonic acid. All the reducing agents formed the complexes of varying stability with Mn ", from which initiating species are produced. 

Compounds which dissolve in concentrated sulphuric acid may be further subdivided into those which are soluble in syrupy phosphoric acid (A) and those which are insoluble in this solvent (B) in general, dissolution takes place without the production of appreciable heat or colour. Those in class A include alcohols, esters, aldehydes, methyl ketones and cyclic ketones provided that they contain less than nine carbon atoms. The solubility limit is somewhat lower than this for ethers thus re-propyl ether dissolves in 85 per cent, phosphoric acid but re-butyl ether and anisole do not. Ethyl benzoate and ethyl malonate are insoluble. 

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