ETHERS AND HETERO-ETHERS OF MORPHINE AND ITS ISOMERS^*

Abstract

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.

The Reduction of Thebaine. Neopine Methyl Ether

“…Dihydroisocodeine methyl ether. For the preparation of this derivative, a-isomorphine-6methyl ether was available from a previous investigation (2). A solution of 2.9 g. of this compound in 40 ml.…”

“…Even after the nature of the new component from thebaine reduction seemed certain, its isolation was long delayed. Attempts to convert neopine methyl ether methiodide back to the tertiary base by the usual (methochloride) method failed, as did the methylation of the 6-hydroxyl of neopine by the method of Mannich (7), which works so well in the series having the 7,8-double bond (2). Separation by salts during eight years of occasional trials resulted in a crystalline picrate mixture of which neopine methyl ether picrate was the more soluble component.…”