No abstract

2-Methoxy-4', 5-bis(carboxymethyl)diphenyl ether, corresponding to the diphenyl ether moiety of the isotetrandrine structure, was prepared by a Willgerodt reaction with 2-methoxy-4', 5-diacetyldiphenyl ether. The latter and 2-methoxy-4', 5-dicarboxydiphenyl ether were prepared by appropriate Ullmann diphenyl ether syntheses.IV. 2,2', 3-TRIMETHOXY-4', 5-BIS(/3-CARBOXYETHYL)DIPHENYL ETHER AND RELATED COMPOUNDS

No abstract

Benzoylation by the Schotten-Baumann procedure converted the diamine to an amorphous dibenzoyl derivative which was apparently associated with two molecules of benzene.

The first article (1) of this series related the synthesis of 2,2',3-trimethoxy-4',5-dicarboxydiphenyl ether (I), and the present paper deals with its conversion to 2,2' ,3-trimethoxy-4', 5-bis(@-aminoethyl)diphenyl ether (11). The diamine (11) represents almost the entire bisisoquinoline portion of the isotetrandrine molecule (111, R = R' = CHJ.Conversion of the dicarboxy ether (I) to the diamino ether (11) was accomplished by the following reactions. Reduction of I to 2,2' ,3-trimethoxy-4' ,5bis(hydroxymethy1)diphenyl ether with lithium aluminum hydride in tetrahydrofuran proceeded in nearly quantitative yield. Treatment of the dialcohol with thionyl chloride afforded the corresponding bis(chloromethy1) derivative in good yield. Difficulty was encountered in preparing the bis(cyanomethy1) compound from the dihalide and no sample of dinitrile could be obtained which did not contain a considerable percentage of residual chlorine. Substituting the bis(bromomethy1) compound for the chloro compound did not improve the reaction with potassium cyanide.Lithium aluminum hydride reduction of the crude dinitrile resulted in a much lower yield (6 %) of I1 than could be accounted for by the impurity of the dinitrile. It is known that formation of insoluble complexes during reduction of nitriles sometimes results in low yields (2). Reduction of the dinitrile with platnum oxide in acetic anhydride (3) afforded 30 % of crude dihydrochloride.