Synthesis of functionalized tetrahydro-1,3-diazepin-2-ones and 1-carbamoyl-1H-pyrroles via ring expansion and ring expansion/ring contraction of tetrahydropyrimidines
Synthesis of functionalized tetrahydro-1,3-diazepin-2-ones and 1-carbamoyl-1H-pyrroles via ring expansion and ring expansion/ring contraction of tetrahydropyrimidines
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DOI：
10.1039/c1ob06284k
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发表时间：
2012-01-01
影响因子：
3.2
通讯作者：
Shutalev, Anatoly D.
中科院分区：
文献类型：
--
作者：
Fesenko, Anastasia A.;Trafimova, Ludmila A.;Shutalev, Anatoly D.
基于1，2，3，4-四氢嘧啶-2-酮在亲核试剂作用下的扩环反应，发展了6-苯硫基取代的2，3，4，5-四氢-1H-1，3-二氮杂-2-酮的合成方法。合成的第一步是由2-苯甲酰氧基乙醛、尿素和对甲苯亚磺酸三组分缩合制得N-[（2-苯甲酰氧基-1-对甲苯磺酰基）乙基]脲。用α-苯硫酮的烯醇化钠亲核取代所得砜中的甲苯磺酰基，然后环化-脱水，脱苯甲酰化得到4-羟甲基-5-苯硫基-1，2，3，4-四氢嘧啶-2-酮，其转化为4-甲磺酰氧基甲基衍生物。后者用亲核试剂如NaCN、丙二酸二乙酯钠、PhSNa、MeONa、NaBH 4、琥珀酰亚胺钠或邻苯二甲酰亚胺钾处理，得到目标多官能化二氮杂卓酮。所得的6-苯硫基-二氮杂卓酮及其6-甲苯磺酰基取代的类似物在酸性条件下由于缩环而转化为3-取代的1-氨甲酰基-1H-吡咯。有效的一锅合成后者从4-甲磺酰氧基甲基-嘧啶实现了使用扩环/缩环序列。
A general approach to 6-phenylthio-substituted 2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones based on the ring expansion reaction of 1,2,3,4-tetrahydropyrimidin-2-ones under the action of nucleophiles has been developed. The first step of the synthesis was preparation of N-[(2-benzoyloxy-1-tosyl)ethyl] urea by three-component condensation of 2-benzoyloxyethanal, urea and p-toluenesulfinic acid. Nucleophilic substitution of the tosyl group in the obtained sulfone with sodium enolates of alpha-phenylthioketones followed by cyclization-dehydration, and debenzoylation gave 4-hydroxymethyl-5-phenylthio-1,2,3,4-tetrahydropyrimidin-2-ones which were transformed into the 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as NaCN, sodium diethyl malonate, PhSNa, MeONa, NaBH4, sodium succinimide, or potassium phthalimide, afforded the target multi-functionalized diazepinones. The obtained 6-phenylthio-diazepinones and their 6-tosyl-substituted analogues were converted into 3-substituted 1-carbamoyl-1H-pyrroles under acidic conditions as a result of ring contraction. Effective one-pot synthesis of the latter from 4-mesyloxymethyl-pyrimidines was realized using a ring expansion/ring contraction sequence.