Synthesis ( IF 2.2 ) Pub Date : 2019-09-13 , DOI: 10.1055/s-0039-1690677 Deblina Roy , Gautam Panda 1
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Abstract
An expeditious, cost-effective synthetic methodology for a wide range of nitrogen-containing unsymmetrical trisubstituted methanes (TRSMs) is reported. The synthesis involves base-mediated 1,6-conjugate addition of heterocyclic amines and amides to substituted para-quinone methides, giving the unsymmetrical TRSMs in moderate to very good yields (up to 83%) in one pot. The low cost, mild temperature, high atom economy and yields, easy scale-up and broad substrate scope are some of the salient features of this protocol. Further, the methodology could be extended for the synthesis of meclizine-, hydroxyzine- and cetirizine-like molecules. The structure of one such compound, 2,6-di-tert-butyl-4-((4-chlorophenyl)(4-methylpiperazin-1-yl)methyl)phenol, was determined by single crystal X-ray analysis.
An expeditious, cost-effective synthetic methodology for a wide range of nitrogen-containing unsymmetrical trisubstituted methanes (TRSMs) is reported. The synthesis involves base-mediated 1,6-conjugate addition of heterocyclic amines and amides to substituted para-quinone methides, giving the unsymmetrical TRSMs in moderate to very good yields (up to 83%) in one pot. The low cost, mild temperature, high atom economy and yields, easy scale-up and broad substrate scope are some of the salient features of this protocol. Further, the methodology could be extended for the synthesis of meclizine-, hydroxyzine- and cetirizine-like molecules. The structure of one such compound, 2,6-di-tert-butyl-4-((4-chlorophenyl)(4-methylpiperazin-1-yl)methyl)phenol, was determined by single crystal X-ray analysis.
中文翻译：
将杂环胺和酰胺的碱介导的1,6-氮杂-迈克尔加成至对-醌醌甲壳素上，从而导致类似美clizine，Hydroxyzine和Cetirizine的体系结构
抽象的
据报道，一种快速，经济高效的合成方法可用于多种含氮不对称三取代甲烷（TRSM）。该合成涉及将杂环胺和酰胺的碱介导的1，6-共轭加成到取代的对醌甲基化物上，在一锅中以中等至非常高的收率（高达83％）得到不对称的TRSM。低成本，温和的温度，高原子经济性和高产率，易于扩大规模和广泛的衬底范围是该协议的一些显着特征。此外，该方法可以扩展用于合成类似美氯嗪，羟嗪和西替利嗪的分子。一种这样的化合物2,6-二酯的结构通过单晶X射线分析确定了丁基-4-（（4-氯苯基）（4-甲基哌嗪-1-基）甲基）苯酚。
据报道，一种快速，经济高效的合成方法可用于多种含氮不对称三取代甲烷（TRSM）。该合成涉及将杂环胺和酰胺的碱介导的1，6-共轭加成到取代的对醌甲基化物上，在一锅中以中等至非常高的收率（高达83％）得到不对称的TRSM。低成本，温和的温度，高原子经济性和高产率，易于扩大规模和广泛的衬底范围是该协议的一些显着特征。此外，该方法可以扩展用于合成类似美氯嗪，羟嗪和西替利嗪的分子。一种这样的化合物2,6-二酯的结构通过单晶X射线分析确定了丁基-4-（（4-氯苯基）（4-甲基哌嗪-1-基）甲基）苯酚。
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