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The cycloaddition reactions of three cyclic imidate esters, 2-ethoxypyrrolin-5-one (6), 2-ethoxyisoindol-3-one (7) and 2-ethoxy-1H-indol-3-one (8) with various 1,3-dipoles were investigated. Dipolarophile 6 added only to nitrile oxides; 8 added to nitrile oxides and to nitrilimines; 7 failed to undergo cycloaddition reactions with either nitrile oxides or nitrilimines.

4,5-Dihydro-2-metyloxazole 1a and 4,5-dihydro-2,4,4-trimethyloxazole 1b, which are examples of cyclic imidate esters, undergo 1,3-dipolar cycloaddition reactions with benzonitrile N-oxide, to give the appropriate 5,6-dihydro-7a-methyl-3-phenyl-7aH-oxazolo[3,2-d]-1,2,4-oxadiazole (2a and 2b respectively). 4,5-Dihydro-2-methylthiazole 1c gives the thia analogue 2c. With alkanoyl and aroyl cyanide N-oxides (RCOCNO), 4,5-dihydro-2-methyloxazole 1a and 4,5-dihydro-2-methylthiazole 1c give the open-chain compounds, RCOXCH2CH2N(CN)COMe (X = O and S respectively).

The cycloaddition reactions of three cyclic imidate esters, 2-ethoxypyrrolin-5-one (6), 2-ethoxyisoindol-3-one (7) and 2-ethoxy-1H-indol-3-one (8) with various 1,3-dipoles were investigated. Dipolarophile 6 added only to nitrile oxides; 8 added to nitrile oxides and to nitrilimines; 7 failed to undergo cycloaddition reactions with either nitrile oxides or nitrilimines.

4,5-Dihydro-2-metyloxazole 1a and 4,5-dihydro-2,4,4-trimethyloxazole 1b, which are examples of cyclic imidate esters, undergo 1,3-dipolar cycloaddition reactions with benzonitrile N-oxide, to give the appropriate 5,6-dihydro-7a-methyl-3-phenyl-7aH-oxazolo[3,2-d]-1,2,4-oxadiazole (2a and 2b respectively). 4,5-Dihydro-2-methylthiazole 1c gives the thia analogue 2c. With alkanoyl and aroyl cyanide N-oxides (RCOCNO), 4,5-dihydro-2-methyloxazole 1a and 4,5-dihydro-2-methylthiazole 1c give the open-chain compounds, RCOXCH2CH2N(CN)COMe (X = O and S respectively).

Substituent chemical shifts for the title systems have been determined at infinite dilution in CDCl3 from a study of 40 derivatives. An excellent correlation is found between the ortho effect of substituents in the thiophene ring and the corresponding effects in thiophene itself, indicating negligible perturbation by the fused rings. Long range effects of 2- and 3-substituents on the 5- and 6-protons are electronic in origin, but cannot be interpreted in terms of simple resonance theory. These long range effects correlate linearly with σp°. An O, S-cis conformation for the formyl group in 2-formyl-thieno[2,3-6][1]benzothiophene is adduced on the basis of chemical shifts.

α-Amino-β-(3-benzo[b]thienyl) propionic acid, the benzo[b]thiophen analogue of tryptophan, has been prepared by reaction of 3-chloromethylbenzo[b]thiophen with diethyl acetamidomalonate or diethyl formamidoalonate, and acidic or alkaline hydrolysis of the product. Its 5-bromo-, 5-chloro-, 5-methyl-, and 5-nitro-derivatives were similarly preprared for pharmacologicl evaluation. (3-Benzo[b]thienyl)acetone, prepared by reaction of 3-benzo-[b]thienylacetyl chloride with diethyl ethozxymagnesium-malonate and acidic hydrolysis of the product, reacted with a mixture of potassium cyanide, ammonium chloride, and ammonium carbonate in aqueous ethanol to give 5-(3-benzo[b]thenyl)-5-methylhydantion alkaline hydrolysis of which gave the benzo[b]thiophen analogue of α-methyltryptophan. Its 5-bromo-, 5-chloro-, 5-methyl-, and 5-nitro-derivatives were prepared similarly.

Monobromination of 6,7-dihyrobenzo [b] thiophen-4(5H)-one in aqueous acetic acid or ether gives mainly the 2- or the 5-bromo-derivative respectively. The 2-bromo-derivative (I; R1= Br, R2= H) reacts further with bromine (1 mol.) in aqueous acetic acid to give the 2,3-dibromo-derivative, and in ether to give the 2,5-dibromo-derivative. Reaction of 2,5-dibromo-6,7-dihydrobenzo[b]thiophen-4(5H)-one with an excess of bromine in acetic acid in the presence of a trace of hydrobromic acid gives a phenolic compound which is probably 2,3,5,7-tetrabromo-4-hydroxybenzo[b]thiophen. The 1H n.m.r. and mass spectra of all the bromo-compounds have been examined.Vilsmeier–Haack reaction of 6,7-dihydrobenzo[b]thiophen-4(5H)-one with N-methylformanilde gives a mixture of the 5-formyl derivative [which is better represented as the hydroxymethylene form (II)[, 6,7-dihydro-4-(N-methylanilino)benzo[b]thiophen-5-carbaldehyde (VI) and the corresponding iminium salt (VII), 2-formyl-6,7-dihydrobenzo[b]thiophen-4(5H)-one, and 4-chloro-6,7-dihydrobenzo[b]thiophen-5-carbaldehyde (VIII). The last compound is the major product (58%) of the reaction of 6,7-dihydrobenzo[b]thiophen-4(5H)-one with phosphoryl chloride and dimethylformamide. Several reactions of the hydroxymethylene compound (II) are described.

Infinite dilution data for six sulphur heterocycles have been obtained from second order analyses of their NMR spectra in CS2, CDCl3, CD3COCD3, or C6D6. Use of LAOCOON3 leads to accurate chemical shifts, but substantial errors remain in some of the coupling constants. Evidence is presented of specific association of chloroform with the sulphur heterocycles and of the interaction of acetone with the sulphur atom. An apparently anomalous geometry for the complex of benzene with thiophen and with other solutes is discussed. Dilution effects are considered in relation to the formation of solute dimers.

Bei der Reaktion zwischen 3-Chlor-1,2-benzisothiazol (II) mit′ NaCN erhalt man anstelle des erwarteten Nitrils (I) 62% 2-Thiocyanato-benzonitril (III), 22% des Disulfids (IV) sowie 6% 2-Acetyl-3-amino-benzo(b)thiophen (V), das uber das Diazoniumsalz zum 2-Acetyl-benzo(b)thiophen (VI) desaminiert wird.

The constitution (IXa) has been established for ψ-rhodomyrtoxin which was isolated from the fruit of the Australian finger cherry, Rhodomyrtus macrocarpa. ψ-Rhodomyrtoxin is a dibenzofuran associated with a 2-methylbutyryl and an isovaleryl residue.

The nuclear bromination, formylation, Friedel–Crafts acylation, and metalation reactions of 1-methylnaphtho-[2,1-b]thiophen occur in the 2-position. Nitration gives a mixture (9 : 1) of the 2- and the 5-nitro-derivatives. The identity of the 5-nitro-derivative is confirmed by its conversion into the corresponding 5-bromo-compound, which is compared with an authentic sample. Nuclear bromination and nitration of 2-methylnaphtho[2,1-b]-thiophen, and the bromination of 1,2-dimethylnaphtho[2,1-b]thiophen and 1-formyl- and 2-formyl-naphtho-[2,1-b]thiophen occur in the 5-position. It is suggested that the lack of reactivity of the 1-position in naphtho-[2,1-b]thiophen and its derivatives may be due to steric interaction with the nearby 9-position.

The oximes of 3-acetylbenzo[b]thiophen and its 5-chloro- and 5-bromo- derivative underwent the Beckmann rearrangement (80–90%). The resulting amides were nitrated to give (80%) the compounds mentioned in the title. On treatment with ferrous oxalate at 225°, each of these gave a mixture of the corresponding 3-cyano-1,2-benzisothiazole and its 3-carbonamide. 5-Chlorobenzo[b]thiophen-2,3-dione was prepared by a standard route from 5-chloro-3-hydroxybenzo[b]thiophen. On treatment with hydrogen peroxide and ammonia it gave 5-chloro-1,2-benzisothiazole-3-carbonamide, which was converted into the nitrile by heating with phosphorus pentoxide. 1,2-Benzisothiazole-3-carbonamide, and the corresponding nitrile, were similarly prepared from benzo[b]thiophen-2,3-dione. The resulting amides and nitriles were identical with those obtained from the ferrous oxalate reactions. 2,3-Diacetamidobenzo[b]thiophen was prepared by the catalytic reduction of 3-acetamido-2-nitrobenzo[b]thiophen, and acetylation of the resulting unstable amine. It was converted into an imidazole derivative by boiling with dilute hydrochloric acid.

Bromination of 2,3-dibromobenzo[b]thiophen in chloroform or acetic acid gives the 2,3,6-tribromo-derivative; nitration gives a mixture of 2,3,6-tribromo-(25%), 2,3,4-tribromo-(3%), 2,3-dibromo-6-nitro-(32%), and 2,3-dibromo-4-nitrobenzo[b]thiophen (36%). Analogous results are obtained for the bromination and nitration of 2,3-dibromo-5-methylbenzo[b]thiophen, except that the presence of the 5-methyl group increases the proportion of the 4-substituted product in each case. The structures assigned are supported by a detailed analysis of their 1H n.m.r. spectra.