Synthesis and reactivity of 4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole. A novel one-pot synthesis of N-substituted indole-2-thiols
Synthesis and reactivity of 4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole. A novel one-pot synthesis of N-substituted indole-2-thiols
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DOI：
10.1021/jo0707784
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发表时间：
2007-07-06
影响因子：
3.6
通讯作者：
Neckers, Douglas C.
中科院分区：
文献类型：
--
作者：
Androsov, Dmitry A.;Neckers, Douglas C.
4-（2-氯-5-硝基苯基）-1,2,3-噻二唑经过开环产生硫烯中间体，该中间体与O-或n -亲核试剂反应，形成芳基取代的硫乙酸的酯或酰胺。硫乙酸衍生物通过亲核取代芳环上卤素的分子间环化得到n -取代的吲哚-2-硫醇（在n -亲核试剂的情况下）或2-烷氧基取代的苯并[b]噻吩（在o -亲核试剂的情况下）。该反应也适用于n -取代吲哚-2-硫醇杂环类似物的合成：以合成1-丁基-1,3-二氢吡咯[2,3-b]吡啶-2-硫酮为例。在硫乙酸钾（一种s亲核试剂）的存在下，4-硝基-2-（1,2,3-噻二唑-4-基）苯硫醇的形成速度比噻二唑的开环速度快，使得杂环对碱具有耐受性。
4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole undergoes ring opening to produce a thioketene intermediate that reacts with an O- or N-nucleophile, forming an ester or an amide of the aryl-substituted thioacetic acid. Intermolecular cyclization of the thioacetic acid derivative via nucleophilic substitution of halogen in the aromatic ring gives an N-substituted indole-2-thiol (in case of an N-nucleophile) or a 2-alkoxy-substituted benzo[b]thiophene (in case of an O-nucleophile). The reaction is also applicable to the synthesis of heterocyclic analogues of N-substituted indole-2-thiols: 1-butyl-1,3-dihydropyrrolo[2,3-b]pyridine-2-thione was synthesized as an example. In the presence of potassium thioacetate (an S-nucleophile) 4-nitro-2-(1,2,3-thiadiazol-4-yl)benzenethiol is formed more quickly than thiadiazole ring opening occurs, making the heterocyclic ring tolerant toward the base.