David J. Wilkins

Chapter 5.5 Five-membered ring systems: With N & S (Se) atoms

Publisher Summary This chapter provides information on five-membered ring systems with N and S (Se) atoms. The chapter presents a discussion on (1) isothiazoles, (2) thiazoles, (3) thiadiazoles, (4) selenazoles, and (5) selenadiazoles. The cycloaddition reactions of both arylalkyl and aryl azides with the isothiazole 1,1-dioxide were found to be highly regioselective, leading to triazines. A variety of interesting ring expansions and annelations of 1,2-benzisothiazoles have been discussed giving rise to new heterocyclic ring systems. Thioamides react under mild conditions with conjugated azoalkenes to give thiazolines that exhibit hydrazono hydrazino tautomerism. Dithiolane isocyanate iminium methylides, are a new type of azomethine methylide derived 1,3-dipole, and undergo efficient and regioselective cycloaddition to thiocarbonyls to yield predominantly thiazolidine-2-thiones. Treatment of the thiadiazole with phenylhydrazine gave the hydrazone, which on methylation with Meerweins reagent gave the thiapentalene. An alternative synthesis of 3,4-disubstituted 1,2,5-thiadiazoles was developed that involved the coupling reaction of 4-substituted 3-halogeno and 3-trifluoromethylsulphonyl 1,2,5-thiadiazoles with arylstannanes in the presence of palladium catalysts to give 4-substituted 3-aryl derivatives in good yields. Trithiazyl chloride (NSC1) 3 has proved to be a versatile molecule for the synthesis of the 1,2,5-thiadiazole ring system.

Regioselective Addition of Grignard Reagents to Isoxazole-4,5-dicarboxylate Esters

Regioselective mono-addition of a range of Grignard reagents with the 5-esters of 3-methylisoxazole-4,5-diesters affords 5-keto derivatives instead of tertiary alcohols which is explained by the complexing ability of the isoxazole oxygen atom and by the electron withdrawing effect of the isoxazole ring.

Use of highly stereospecific 1,3-dipolar cycloadditions of cyclic nitrones with acetylenes in the preparation of novel heterocyclic ring systems

Cyclic nitrones with substituents α to the nitrogen atom undergo 1,3-dipolar cycloadditions in a stereo- and regio-specific manner with acetylenes. The nitrone 3 reacts with methyl propiolate, methyl phenylpropiolate and methyl acetylpropiolate to give the corresponding pyrrolo[1,2-b]isoxazoles 5, 8 and 13 respectively. Compound 13 reacts with 4-chlorophenylhydrazine to afford the pyrazolo[4,3-a]pyrrolizine 15 by a novel rearrangement. The nitrone 18 undergoes a 1,3-dipolar cycloaddition with methyl propiolate in a stereo- and regio-specific manner to give the isoxazolo[2,3-a]pyridine 19. The nitrone 18, when reacted with methyl acetylpropiolate, gives a mixture of regioisomers in a ratio of 3∶2. The major regioisomer 21 reacts with 4-chlorophenylhydrazine to afford the novel pyrazolo[4,3-a]indolizine ring system 23. The bicyclic nitrone 26 reacts with methyl propiolate and methyl acetylpropiolate to give the cycloadducts 27 and 28 respectively; both these compounds contain the novel isoxazolo[3,2-i]indole ring system.