Malonic acid, ethyl half ester

DI-ier<-BUTYL ESTER, 34, 26 Malonic acid, ethyl half ester, 37,34 Malonic acid, ethylidene, diethyl ESTER, 32, S4... 

CH3.(CH2)2.C(C02.C2H5XC0.N3) mw 198.23 N 21.20% OB to C02 -153.36% ypl oil, expl. Sol in eth and CC14. Prepn is by reacting the K salt, of the half (or mono) ethyl ester of propyl malonic acid with nitrous acid Refs 1) Beil, not found 2) T. Curtius W, Lehmann, Transformation of alkylated malonic acids into a-amino acids. III. Synthesis of cr-aminovaleric acid, propylmalonylazidic acid. . JPraktChem 125, 211-302 (1930) CA 24, 3215(1930)... 

A large number of trialkylacetic acid esters have been prepared by mixed Kolbe electrolysis of ethyl malonates [164]. Crossed-coupling is also used for chain extension. Extension by two carbon atoms is achieved with benzyl succinates [153, 180-182], whereby the purification of the chain extended fatty acid is simphfied by using the benzyl half ester [181a]. 

The magnesium enolates are prepared by treatment of malonic acid half ester either with magnesium ethylate[24],[32] or with isopropylmagnesium bromide[24] or chloride.t26] Ref. [23] describes the synthesis of a 13C-labelled ethyl acetoacetate. Concerning the synthesis of porphyrin / -ketoesters,[3 1 it was noticed that the method via imidazolides is more efficient than the other approach via acid chlorides and sodiomalonic esters. 

However, Battersby and Openshaw (52) supplied proof of the nuclear structure of these alkaloids in a total synthesis of dl-rubreme-tihium bromide, although the synthesis did not fix the double bonds in unambiguous positions. The half ester chloride of malonic acid was condensed with 3,4-dimethoxyphenethylamine, the amide cyclized with phosphorus pentoxide, and the derived dihydroisoquinoline reduced to XLVII. The latter was condensed with ethyl a-aldehydobutyrate and the mixture reduced to XLVIII, which by Dieckmann condensation... 

An alternative preparation of a nitrile is illustrated by the reaction of the half-ester of 2,2-diethyl malonate 1.51) ivith SOCI2 and then NH3 to give the amide. Subsequent heating with phosphorus pentoxide led to dehydration and gave nitrile 1.52 Catalytic hydrogenation reduced the nitrile to an aminomethyl group, and acid hydrolysis gave 2,2-diethyl-3-aminopropanoic acid 1.53). 2-Ethyl-2-cyclohexyl-3-aminopropanoic acid and 2-ethyl-2-benzyl-3-aminopropanoic acid were also prepared by this method.30... 

Both aldehydes or ketones can be condensed with malonate derivatives, but ammonia can be used as a base rather than pyridine. Reaction of butanal with ammonia in the presence of the half-ester of malonic acid, for example, gave ethyl... 

Cyclobutanedicarboxylic acid has been prepared by hydrolysis of the ethyl ester,1 or of the half nitrile, 1-cyano-l-car-boxycyclobutane.2 The ethyl ester has been prepared by condensation of ethyl malonate with trimethylene bromide1 or chloro-bromide.3 The half nitrile has been prepared by condensation of trimethylene bromide with ethyl cyanoacetate followed by hydrolysis of the ester to the acid.2... 

Diethyl phenyl ethyl malonate. 1 mole of benzyl cyanide is added dropwise to a solution of 1 mole of ethyl carbonate in 2 liters of anhydrous ethanol containing 5 g of clean sodium metal. This mixture is refluxed (preferably on a steam bath) for 5 hours. It is then cooled and to it is added a cooled mixture of 40 g of sulfuric acid in 100 ml of anhydrous ethanol. This alcoholic solution is refluxed for 5 hours, cooled, neutralized with sodium ethylate (use external indicator). The mixture is evaporated to half bulk, filtered from the sodium sulphate and to it is added 1 mole of clean metallic sodium. Reflux while adding 1 mole of ethyl bromide dropwise. Heat for another 2 hours after the addition is completed. Remove the alcohol by distillation and dissolve the remaining residue in water. Extract the substance from the water with benzene and after drying, the benzene is recovered and the ester should be purified by distilling in vacuo. 

Stepwise Degradation to Amino Adds. There are several approaches to the transformation of a di- or poly-carboxylic acid to an amino acid. The most satisfactory procedure makes use of the ester acids and their salts. They react with hydrazine to form hydrazide acids, which may be degraded through the azide acids to amino acids. From substituted malonic esters a-amino acids are obtained. (For the preparation of a-amino acids from substituted cyanoacetic esters, see p. 359.) Thus, the potassium salt of the monoethyl ester of methylmalonic acid, which is prqjared by half hydroly of the diethyl ester, pves alanine ethyl ester hydrochloride in 67% yield. Many other amino acids have... 

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