Bridgehead nitrogen spiroheterocyclic systems: Synthesis, stereochemistry and antimicrobial activity of spiro [(1'<i>R</i>)-bicyclo[2.2.1] heptane-2' ,3-( 4' H)-[2H]-thiazolo[3,2<i>-b</i>]-<i>s</i>-tetrazines] and spiro[(1'R)-bicyclo[2.2.1]heptane-2' ,3-(4' <i>H</i>)<i>- </i>[2H]-pyrazolo[3',4':4,5]-thiazolo[3,2-<i>b</i>]-<i>s</i>-tetrazines]

Abstract

The synthesis of (1'<i>R</i>)-6-(<i>p</i>-bromophenyl)-1',7',7'-trimethylspiro[bicyclo[2.2.1] heptane-2',3-( 4<i>H</i>)-[2<i>H</i>]-thiazolo[3,2-<i>b</i>]-<i>s</i>-tetrazine] hydrobromide <b>2</b> and (1'R)-1.2,4,5-tetrahydro-1',7',7'-trimethylspiro [bicyclo[2.2.1]heptane-2',3-(4H)-[2H]-thiazolo[3,2-<i>b</i>]-<i>s</i>-tetrazine]-6(7<i>H</i>)-one 3 have been accomplished by the reaction of (1'<i>R)-</i>1,2, 4, 5-tetrahydrospiro-1',7',7' trimethylspiro [bicyclo[2.2.1]heptane-2',3 -<i>s</i>-tetrazinel-6-thione <b>1</b> with <i>p</i>-bromophenacylbromide and chloroacetic acid respectively. (1'<i>R</i>)-7-<i>p</i>-Arylidene -1',7',7'trimethylspiro[bicyclo[2.2.1]heptane-2',3-(4<i>H</i>)-[2<i>H</i>]thiazolo[3,2<i>-b</i>]<i>s</i>- tetrazine]-6(7<i>H</i>)-one <b>4</b> has been prepared either by the condensation of <b>3</b> with aldehyde or in a single-step by the reaction of <b>1</b> with ethyl chloroacetate and aldehyde in the presence of pyridine and piperidine. Condensation of <b>4</b> with 2,4-dinitrophenylhydrazine in the presence of anhydrous sodium acetate furnishes (1'<i>R</i>)-8-(<i>p</i>-anisyl)-7-(2,4-dinitrophenyl)-cis-8, 8a-dihydrospiro [bicyclo[2.2.1]heptane-2',3-(4<i>H</i>)-[2<i>H</i>]-pyrazolo[3',4': 4,5]thiazolo[3,2-<i>b</i>]-<i>s</i>-tetrazine] <b>5</b>. The antibacterial and antifungal activities of some of the compounds have also been evaluated.