No abstract

March, 1951 POLYAMIDES FROM FORMALDEHYDE AND DINITRILES 1031 cake was slurried successively with 600.ml. each of water and ethyl alcohol. The combined filtrate was evaporated a t 15 mm. Presswe by warming on a water-bath (not above 65'). A white solid remained weighing 90.5 g. (86%) after drying in a vacuum desiccator. The crude methylene-bisacrylamide was recrystallized from a mixture of 300 cc. of acetone and enough water (about 75 cc.) to dissolve the product in the hot solution. The white solid that separated from the cooled solution weighed 71 g. (67.6% yield of purified material) , m.p. 185' with polymerization.

The halogenomorphides and halogendcodides are formed when the secondary alcoholic hydroxyl group of morphine or codeine is replaced by a halogen atom. Although the compounds occupy a position of considerable importance in the development of the morphine structural theory, and are the source of the morphine and codeine isomers, there has been no direct proof of structure offered for any single member of the series.The related pair, -chloromorphide and -chlorocodide, are the principal products obtained when morphine and codeine, respectively, are treated with thionyl chloride or phosphorus pentachloride. The halogen atom has tacitly been assumed to take the place of the hydroxyl that is known to occupy the 6-position, although it has been shown (1,2,3) in recent years that replacement of a group at this point in the nucleus often involves an a,7-shift, as a result of which the new group may appear at position 8. In carrying out numerous kilogram-scale preparations, we have observed that the a compounds are not the only products of the reaction, but are accompanied by the ß-halogeno derivatives to the extent of 10% to 15% of the total yield. In the codeine series, a-and 0-chlorocodides were obtained in part in the form of a new molecular compound of constant properties, that could not be separated into the components by fractional crystallization, although a-and ß-chlorocodides themselves differ considerably in solubility. Separation through salts, a method previously employed successfully for similar molecular compounds in the 1 The work reported in this paper is part of a unification of effort by a number of agencies having responsibility for the solution of the problem of drug addiction.

As part of an investigation on the relationship between constitution and physiological action, a series of 21 new ethers of morphine, of a-, ß-, and 7-isomorphines, and of their dihydro derivatives has been synthesized. This series includes both phenolic and alcoholic ethers (heteroethers). New ethers of benzylmorphine, benzyldihydromorphine, and of dihydrodesoxymorphine-D are described.

Tetrahydro-e-methylmorphimethine (Phenolic) Methyl Ether (V).-This base was prepared in quantitative yield from III-methiodide by the thallium hydroxide degradation described under base VII. It crystallizes as rectangular scales from acetone, m. p. 156.5-157°( corr.); ¡«Id +199°(alcohol, c = 0.80).