Synthesis and reactions of oxygen and nitrogen heterocycles..

Abstract

The thesis is entitled “Synthesis and Reactions of Oxygen and Nitrogen Heterocycles” and is presented in five chapters. Chapter I deals with the synthesis of spironaphthalenones (1b) and (1c). 4-Methyl-2-naphthol was prepared from m-cresol methyl ether by succinoylation, Clemmensen reduction, cyclisation, borohydride reduction, dehydration, and aromatisation, followed by demethylation. This was converted to the bis-naphthol (2) by condensation with the sodium salt of 6-naphthol-1-methyl-sulphonic acid. Potassium ferricyanide oxidation of (2) gave the required spironaphthalenones (1b) and (1c). Chapter II is concerned with the DDQ oxidation of a few spironaphthalenols (3), which resulted in the formation of naphthofuran derivatives (4). Sodium borohydride reduction of spironaphthalenone (1a) gave the allylic alcohol (3a). DDQ oxidation of (3a) in benzene resulted in smooth transformation to a mixture of cis- and trans-?,?-unsaturated aldehyde (4a). Grignard reaction of (1a) with methylmagnesium iodide and phenylmagnesium bromide gave the allylic alcohols (3b) and (3c) respectively. Similar oxidation of these compounds gave the unsaturated ketones (4b) and (4c) as cis- and trans-isomers. Structures of these compounds were established using spectral data. An attempted synthesis of isomers (5) and (6) of olivacine is discussed in Chapter III. The starting aldehyde (7) was prepared from N-benzyl tetrahydrocarbazole by Vilsmeier reaction. Reaction of this aldehyde (7) with aminoacetone dimethyl ketal, followed by borohydride reduction, gave the amine (8a). Tosylation with p-toluenesulphonyl chloride in triethylamine resulted in the formation of the corresponding tosylate (8b). Mild acid hydrolysis of (8b) gave the tosyl ketone (8c). However, treatment of the ketone (8c) with HCl-dioxane or P?O?-benzene did not result in cyclisation but gave the cleaved N-tosyl aminoacetone. After briefly reviewing the Vilsmeier reaction of heterocycles, the Vilsmeier reaction of 5,6,7,8-tetrahydroisoquinoline derivatives has been discussed in Chapter IV. Thus, Vilsmeier reaction of 5,6,7,8-tetrahydroisoquinoline (9a) gave three compounds identified as 9d, 9e, and 10, based on spectral data. Plausible mechanisms for the formation of these compounds have been suggested. Vilsmeier reaction of the corresponding dihydroxy compound (9b), followed by methylation, resulted in the formation of two distinct compounds for which structures 9f and 11 have been proposed, based on a detailed study of their spectral characteristics. Vilsmeier reaction of (9c) followed by methylation was found to give (9g). Nuclear Overhauser studies ruled out alternate structures for these compounds. Chapter V deals with the potassamide in liquid ammonia reaction of 5,6-dihydroisoquinolines (12a and 12b), followed by in situ alkylation with alkyl halides. Thus, reaction of 12a with KNH? in liquid ammonia, followed by addition of methyl iodide in situ, gave rise to C-alkylated 5,6-dihydroisoquinolines (12c and 12d) and another dihydroisoquinoline (13). Alkylation of 12b by potassamide reaction with alkyl halides (CH?I and C?H?I) gave similar products.