Chemical constitution and hypnotic action : acid amides and products of the condensation of malonamides and malonic esters / by F.G.P. Remfry.

  • Remfry, Frederic George Percy.
Date:
1911
Catalogue details

Licence: In copyright

Credit: Chemical constitution and hypnotic action : acid amides and products of the condensation of malonamides and malonic esters / by F.G.P. Remfry. Source: Wellcome Collection.

Provider: This material has been provided by The Royal College of Surgeons of England. The original may be consulted at The Royal College of Surgeons of England.

    8/19 (page 614)
    Water is then split off with closing of the ring, and hydrolysis of the remaining ester, and subsequent elimination of carbon ■dioxide, next occurs: co2h-ch2-c<_ CO CO >CHR -> CH,C<^g>CHR. A similar loss of carbon dioxide, due to the action of sodium ethoxide, was observed by Einhorn (Annalen, 1908, 359, 145), who found that the anhydride of diethylmalonic acid, when thus treated, .gave ethyl diethylmalonate, ethyl hydrogen diethylmalonate, and ethyl diethylacetate. The condensation of malonamides with malonyl chlorides leads ±o results similar to those obtained with the esters. In the case of -the unsubstituted malonamide, a normal condensation product is obtained, but dialkylmalonamides again yield condensation products, from which carbon dioxide has been eliminated. Thus dipropyl- malonvl chloride and malonamide (2 mols.) give dipropylmalonyl- dimalonamide (X), whilst the same acid chloride and dipropylmalon- amide give 4 : 6-diketo-5 : h-dipropyl - 2 - a - propylbutyltetrahydro- vyrimidine (XI) : C3H7^r-^CO'NH'CO-CH‘’,CO'NH2 •CgH^^CONH-CO-CH'-CO-NHa (X.) ^J>CH-C< NH-CO N-—CO >C< C,H7 c3h7’ (XI.) the formation of the latter being analogous to that of the pyrimidine •depicted in the last equation. It has now been shown that an eight-membered ring is not formed when malonic ester or a substituted malonic ester is condensed with a substituted malonamide, but only when it is condensed with •malonamide itself. Even the latter reaction, however, has its limits, malonamide condensing readily only with monoalkyl- and -dimethyl-malonic esters. With methylethylmalonic esters it con- denses to the eight-membered ring only with difficulty, and with diethyl- and higher dialkyl-malonic esters condensation takes place with the formation of substances which have entirely different properties from either the malonylmalonamide or pyrimidine compounds. In this connexion the results of Meyer (Ber., 1906, 39, 198) on the influence of the size of alkyl groups on the formation of amides from malonic esters are of interest. He shows that in a disubsti- tuted malonic ester at least two ethyl groups, either in the esters or attached to the quaternary carbon atom, are necessary to prevent reaction between the ester and aqueous ammonia. In the present