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Open Access Thesis

Keywords

Dihydropyridine;

Abstract

Dihydropyridines, which were first studied by Hantzsch in 1882, now bear his name. A new synthesis of Hantzsch 's base, 2,6-dimethyl-3,5-dicarboethoxy-l ,4- dihydropyridine (lb), was discovered. The preparation of Hantzsch's base (lb) from new starting materials, ethyl acetoacetate (3) and chloromethylmethyl ether (4), was described. Ethyl acetoacetate was reacted with sodium amide in liquid ammonia followed by chloromethylmethyl ether to form the 2,6-dimethyl-3,5-dicarboethoxy1,4-dihydropyridine (lb) in 84% overall yield. Compound (lb) was further identified by its oxidation to the corresponding pyridine, 2,6-dimethyl-3,5-dicarboethoxypyridine ( 11 b) by glacial acetic acid. A mechanism for the formation of the compound ( 1 b) was proposed. It was proposed that ethyl acetoacetate was deprotonated by sodium amide to give an enolate anion intermediate (34). The enolate anion reacted with chloromethylmethyl ether to form ethyl 2-methoxymethyl acetoacetate (35). The intermediate (35) spontaneously coupled with another enolate anion to give the diethyl þÿ±,±'-diacetylglutarate (27). The 1,5-ketone, (27), in the liquid ammonia, undergoes cyclization to yield the expected 1,4-dihydropyridine (lb). The proposed intermediate (27) was prepared by a different synthetic method and it was demonstrated that this compound did, indeed, yield the 1 ,4-dihydropyridine when placed under the original reaction conditions. The structures of the intermediate and the final compound were determined by a combination of infrared, 300 MHz 1 H and 75 .4 MHz 13C nmr spectroscopy.

Year of Submission

1993

Degree Name

Master of Arts

Department

Department of Chemistry

First Advisor

James G. Macmillan

Second Advisor

Kate E. Doan

Third Advisor

Kirk P. Manfredi

Comments

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Date Original

1993

Object Description

1 PDF file (66 leaves)

Language

en

File Format

application/pdf

Included in

Chemistry Commons

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