甲基三嗪及其脲类衍生物的合成和生物活性研究
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摘要
含氮杂环化合物在医药、农药的研究开发中占据十分重要的地位,其中脲类化合物因其对(-分泌酶有很好的抑制作用,对乙酰乳酸合成酶/乙酸羟酸合成酶的抑制作用以及对杂草光合成的抑制作用等,在医药,农药中有一定的应用,也可以作为农药的先导结构。同时化合物三聚氯氰因其具有多个反应中心,因而显出其重要和特殊的化学性质,在很多有机合成及生物代谢过程中起着承上启下的中间体作用。为此我们从三聚氯氰开始,对具有生物活性的脲类化合物的合成进行了研究,合成了N-磺酰基-N’-甲基三嗪脲和一系列N-芳基-N’-甲基三嗪脲新化合物,并进行了生物活性方面的初步研究。
本文研究了卤甲烷与金属镁在晶体碘的催化下,反应生成格氏试剂甲基卤化镁的方法;研究了甲基卤化镁与三聚氯氰发生格氏反应生成2,4-二氯-6-甲基-1,3,5-三嗪的方法,收率在60%以上;研究了2,4-二氯-6-甲基-1,3,5-三嗪与甲醇钠反应,生成2-甲基-4,6-二甲氧基-1,3,5-三嗪的方法,收率在90%以上;研究了2-甲基-4,6-二甲氧基-1,3,5-三嗪与甲胺反应生成2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪的方法,收率在80%以上。所合成得到的产品——2,4-二氯-6-甲基-1,3,5-三嗪、2-甲基-4,6-二甲氧基-1,3,5-三嗪、2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪,经熔点测定、元素分析、IR和1H-NMR分析证明与预期结构相符。
研究了芳胺或磺酰胺光化反应,合成相应的异氰酸酯的方法,产率在92%以上;研究了异氰酸酯与与2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪在溶剂的作用下,合成2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪的非对称取代脲的方法,产率在78%以上。所合成得到的产品——N-甲基-N-(4-甲基-6-甲氧基-1,3,5-三嗪-2-基)-N’-(2,3,4-三氟苯基)脲、N-甲基-N-(4-甲基-6-甲氧基-1,3,5-三嗪-2-基)-N’-(2,3,4,5-四氟苯基)脲、2-[4-甲氧基-6-甲基-1,3,5-三嗪-2-甲基氨基甲酰氨基磺酰基]苯甲酸甲酯,经元素分析、IR和1H-NMR分析证明与预期结构相符。
所合成的系列N-芳基-N’-甲基三嗪脲的生物活性测试工作正在进行中。
Heterocyclic compounds as medicines and pesticides have been developed most quickly and have become the new trend in the development. In the new developed medicines and pesticides heterocyclic compounds are the most important domain. Ureas show biological activities of theγ-Secretase inhibitors and ALS/AHAS inhibitors, and weed photosynthesis inhibitors.
2,4,6-Trichloro-1,3,5-triazine is the one kind of the most important intermediate in the fields of the organic synthesize and which play essential roles in some biosynthetic and metabolic pathways. In this thesis, the method for preparation of bioactivity compounds ureas from 2,4,6-trichloro-1,3,5-triazine has been studied and their bioactivity has also been tested.
Methyl halides are reacted with magnesium catalyzed by crystalline iodine, which afford methylmagnesium halides. Methylmagnesium halides perform Grignard reaction with 2,4,6-trichloro-1,3,5-triazine, which gain 2,4-dichloro-6-methyl-1,3,5--triazine. Methods for preparation of 2,4-dimethoxy-6-methyl-1,3,5-triazine and 2-methoxy-4-methylamine-6-methyl-1,3,5-triazine have been studied. Their yields are about 60-95%. The structures of these productions have been confirmed by elemental analyst, IR, 1H-NMR which showed that the structures of these compounds are the same as desired.
Phosgenation of aryalamines or sulfonylamines produce corresponding isocyanates, which are condensed with 2-methoxy-4-methylamine-6-methyl-1,3,5-tri--azine, which afford corresponding ureas. Their yields are about 80%. The structures of these productions have been confirmed by elemental analyst, IR, 1H-NMR which showed that the structures of these compounds are the same as desired.
The bioactivities of ureas in this thesis are being tested.
本文研究了卤甲烷与金属镁在晶体碘的催化下,反应生成格氏试剂甲基卤化镁的方法;研究了甲基卤化镁与三聚氯氰发生格氏反应生成2,4-二氯-6-甲基-1,3,5-三嗪的方法,收率在60%以上;研究了2,4-二氯-6-甲基-1,3,5-三嗪与甲醇钠反应,生成2-甲基-4,6-二甲氧基-1,3,5-三嗪的方法,收率在90%以上;研究了2-甲基-4,6-二甲氧基-1,3,5-三嗪与甲胺反应生成2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪的方法,收率在80%以上。所合成得到的产品——2,4-二氯-6-甲基-1,3,5-三嗪、2-甲基-4,6-二甲氧基-1,3,5-三嗪、2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪,经熔点测定、元素分析、IR和1H-NMR分析证明与预期结构相符。
研究了芳胺或磺酰胺光化反应,合成相应的异氰酸酯的方法,产率在92%以上;研究了异氰酸酯与与2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪在溶剂的作用下,合成2-甲基-4-甲胺基-6-甲氧基-1,3,5-三嗪的非对称取代脲的方法,产率在78%以上。所合成得到的产品——N-甲基-N-(4-甲基-6-甲氧基-1,3,5-三嗪-2-基)-N’-(2,3,4-三氟苯基)脲、N-甲基-N-(4-甲基-6-甲氧基-1,3,5-三嗪-2-基)-N’-(2,3,4,5-四氟苯基)脲、2-[4-甲氧基-6-甲基-1,3,5-三嗪-2-甲基氨基甲酰氨基磺酰基]苯甲酸甲酯,经元素分析、IR和1H-NMR分析证明与预期结构相符。
所合成的系列N-芳基-N’-甲基三嗪脲的生物活性测试工作正在进行中。
Heterocyclic compounds as medicines and pesticides have been developed most quickly and have become the new trend in the development. In the new developed medicines and pesticides heterocyclic compounds are the most important domain. Ureas show biological activities of theγ-Secretase inhibitors and ALS/AHAS inhibitors, and weed photosynthesis inhibitors.
2,4,6-Trichloro-1,3,5-triazine is the one kind of the most important intermediate in the fields of the organic synthesize and which play essential roles in some biosynthetic and metabolic pathways. In this thesis, the method for preparation of bioactivity compounds ureas from 2,4,6-trichloro-1,3,5-triazine has been studied and their bioactivity has also been tested.
Methyl halides are reacted with magnesium catalyzed by crystalline iodine, which afford methylmagnesium halides. Methylmagnesium halides perform Grignard reaction with 2,4,6-trichloro-1,3,5-triazine, which gain 2,4-dichloro-6-methyl-1,3,5--triazine. Methods for preparation of 2,4-dimethoxy-6-methyl-1,3,5-triazine and 2-methoxy-4-methylamine-6-methyl-1,3,5-triazine have been studied. Their yields are about 60-95%. The structures of these productions have been confirmed by elemental analyst, IR, 1H-NMR which showed that the structures of these compounds are the same as desired.
Phosgenation of aryalamines or sulfonylamines produce corresponding isocyanates, which are condensed with 2-methoxy-4-methylamine-6-methyl-1,3,5-tri--azine, which afford corresponding ureas. Their yields are about 80%. The structures of these productions have been confirmed by elemental analyst, IR, 1H-NMR which showed that the structures of these compounds are the same as desired.
The bioactivities of ureas in this thesis are being tested.
引文
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