The condensation of hydrazines and [beta]-diols with 2,5-hexanedione and 2,5-diethoxytetrahydrofuran


The objective of this series of investigations was two-fold: (1) to investigate new synthetic routes to the sterically hindered amines and hydrazines, and (2) the preparation of potential hypotensive and anticholinergic agents to be screened for pharmacological activity. A series of N-(substituted amino)-2,5-dimethylpyrroles was synthesized by means of the Knorr-Paal condensation, and the N-alkylamino analogs were found to undergo catalytic hydrogenation to the corresponding pyrrolidines, while the N-arylamino compounds underwent no reaction or yielded to N-N bond cleavage, depending upon severity of the conditions. In applications expanding upon the fundamental ground-work laid by Broadbent and Olsen^1 a series of 4-substituted 1,7-dimethyl-2,6-dioxa-10-azatricyclo[^4,10]decanes was prepared by the interchange reaction of sterically hindered carboxylic and carbamic acid esters with 1,7-dimethyl- 4-hydroxymethyl-2,6-dioxa-10-azatricyclo[,10]decane. Other exploratory work in this area resulted in the preparation of the 4-ethoxymethyl analog of the tricyclic nucleus by the Williamson synthesis. A correlation was made between the synthesis of the 1,7-dimethyl-2,6-dioxa-10-azatricyclo[^4,10]decanes by condensation of 2-amino-1,3-propanediols with 2,5-hexanedione and the more common Knorr-Paal reaction of primary amines with the same diketone. These results indicated that both pathways were functioning simultaneously in the condensation of 2-amino-1,3-propanediols with Υ-diketones or their equivalent, production of the tricyclic system taking preference over pyrrole formation when the effects of steric hindrance become operative. As an outgrowth of studies directed toward the synthesis of analogous heterotricyclic systems a family of 2,2'- ethylenebis(1,3-dioxanes) was prepared. The 5-amino-5- methyl compound of this series was found to form a stable N-bromo derivative and is undergoing further consideration in regard to this property. These investigations also led to the synthesis of the parent compound of the 2,2'-ethylenebis(1,3-dithiane) series. All compounds synthesized during the course of this research have been submitted to private industry for pharmacological screening as well as to the Cancer Chemotherapy National Service Center. Pharmacological data resulting from this work is not currently available for public use.



College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry



Date Submitted


Document Type





Chemistry, Organic, Chemotherapy, Pyrroles, Dioxane



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