3-Chloro-2,1-benzisothiazole
(2; R = H, R? = Cl) and 3,5-dichloro-2,1- benzisothiazole (2;R,R? = Cl)
react readily with nucleophiles, and yield 3-substituted products. Acid
hydrolysis of one such product, ethyl (2,1-benzisothiazol-3-yl)cyanoacetate (2;
R = H, R? = CH(CN)CO2Et),affords (2,1-benzisothiazol-3-yl)acetic
acid (2; R = H, R? = CH2CO2H), an auxin
analogue.
2.1 -Benzisothiazoles react readily with dialkyl sulphates, alkyl bromides, and alkyl toluene-p-sulphonates at 11 5-1 20" to yield quaternary salts. Such salts are decomposed by aqueous acid or base, affording N-substituted o-aminobenzaldahydes ; the parent o-aminobenzaldehyde can be obtained from the product of the reaction between 2.1 -benzisothiazole and ethyl chloroformate. Bridged binuclear o-aminobenzaldehydes may also be prepared.UNTIL recently, reports of quaternary salts of 2,lbenzisothiazoles were of 3-amino-or 3-azo-substituted derivatives only.24 However, a recent paper 5, gives details of the preparation and ring-opening reactions of simple 2,l-benzisothiazole quaternary salts. The work we now describe, completed before the appearance of this paper: extends the scope of such reactions.2,l-Benzisothiazole itself (I; R1 = H) and its simple derivatives afford quaternary salts (11) in good yield on direct heating with dialkyl sulphates, alkyl bromides, or alkyl toluene-P-sulphonates. The salts (11) are usually obtained as colourless crystalline solids by this procedure; in some cases, however, the salt is obtained asan oil, and is best isolated as the orange crystalline iodide by treatment with aqueous sodium iodide solution.
The reductive alkylation of 3‐aminomethylbenzo[b]thiophene by the Eschweiler‐Clarke (formaldehyde‐formic acid) method and of 3‐β‐aminoethylbenzo[b]thiophene by the Borch (formaldehyde‐cyanoborohydride) method proceeded in good yields. However, the Eschweiler‐Clarke reaction with 3‐β‐aminoethylbenzo[b]thiophene gave the Pictet‐Spengler cyclized product, N‐methyl‐1,2,3,4‐tetrahydrobenzo[b]thieno[2,3c]pyridine. Mechanistic aspects of the latter reaction were investigated.
The rates of quaternization of the title compounds with dimethyl sulphate are reported. The reactivity order is Se > NMe > S > O; benzofusion
has only a small rate-diminishing effect.
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