CN1173952C - 一种n-羟基脒类化合物的制备方法 - Google Patents

一种n-羟基脒类化合物的制备方法 Download PDF

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CN1173952C
CN1173952C CNB021392110A CN02139211A CN1173952C CN 1173952 C CN1173952 C CN 1173952C CN B021392110 A CNB021392110 A CN B021392110A CN 02139211 A CN02139211 A CN 02139211A CN 1173952 C CN1173952 C CN 1173952C
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hydroxyamidines
nitrile oxide
halopyridine
butyl dicarbonate
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CN1405154A (zh
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闯 石
石闯
姜中兴
曾艳
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Wuhan University WHU
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Abstract

N-羟基脒类化合物的制备方法，将2位、4位或6位的卤代吡啶化腈在无水乙醇中与无水哌嗪作用生成含1位哌嗪基的吡啶化腈类化合物；然后利用二碳酸二叔丁酯进行单氨基保护；再与盐酸羟胺、碱金属的碳酸盐反应生成N-羟基脒类化合物。本发明提供的上述制备方法简单而且所得产物的产率较高。

Description

一种N-羟基脒类化合物的制备方法
技术领域
本发明涉及一种N-羟基脒类化合物的制备方法。
背景技术
结构式为
Figure C0213921100031
式中X＝H或Boc-t的N-羟基脒类化合物，有三个具有生理活性的基团，是药物中间体。本化合物属于哌嗪类化合物，而哌嗪类化合物具有不同程度的5-羟基色胺受体阻断活性，并且其哌嗪部分可与其他部分相结合可使化合物具有中枢和外周降压活性。该化合物属于一种N-羟基脒类化合物，而脒类化合物具有潜在的杀菌作用。该化合物是合成1，2，4-噁二唑和芳杂环硫脲类化合物的重要中间体。1，2，4-噁二唑类衍生物具有良好的生物活性，其应用广泛，如杀虫、杀螨、杀菌及制药等。目前尚未发现有关该化合物合成的报导。
发明内容
本发明就是针对上述问题提供该种N-羟基脒类化合物的制备方法，这种方法简单而且产率较高。
本发明提供的技术方案是：结构式为
Figure C0213921100032
式中X＝Boct的N-羟基脒类化合物的制备方法，将2位、4位或6位的卤代吡啶化腈在无水乙醇中与无水哌嗪作用生成含1位哌嗪基的吡啶化腈类化合物；然后利用二碳酸二叔丁酯进行单氨基保护；再与盐酸羟胺、碱金属的碳酸盐反应生成N-羟基脒类化合物。其反应式如下：
Figure C0213921100041
式中R1＝Cl，Br，I     R2＝CN 
Figure C0213921100042
本发明采用保护的哌嗪与卤代吡啶反应，利用吡啶自身的强的电子诱导效应，使哌嗪与之发生亲核取代反应。本发明提供的上述制备方法简单而且所得产物的产率较高。
具体实施方式
本发明将2位、4位或6位的卤代吡啶化腈在无水乙醇中与无水哌嗪作用生成含1位哌嗪基的吡啶化腈类化合物；在二氯甲烷和碱性条件下，加入含二碳酸二叔丁酯的二氯甲烷液，将哌嗪的另一个氮保护；最后将其与盐酸羟胺、碱金属的碳酸盐反应生成N-羟基脒类化合物。
实施例：以2位的卤代吡啶化腈为原料制备N-羟基脒类化合物(以4位或6位的卤代吡啶化腈为原料制备N-羟基脒类化合物的方法与之类同)的反应式如下：
Figure C0213921100043
在5000mL三口烧瓶中加入220克的3-氰-2-氯吡啶，用3200mL无水乙醇溶解。待溶解完毕后，在加入688克的无水哌嗪，室温反应20h，蒸馏除去大部分乙醇，在向其中加入3000mL水，用二氯甲烷萃取。所得二氯甲烷液用无水硫酸钠干燥。蒸馏除去二氯甲烷，所得固体用无水乙醇重结晶，得220克的A，产率为：73.6％。
在5000mL三口烧瓶中加入160克的A，用3000mL的二氯甲烷溶解。待其溶解完毕之后，再加入220克的二碳酸二叔丁酯。搅拌让其溶解，溶解完毕之后，继续搅拌0.5h，再滴加232mL的三乙胺。滴加完毕之后，反应过夜。停止反应，用水洗二氯甲烷液两次，用无水硫酸钠干燥。蒸出二氯甲烷，用乙醇和石油醚重结晶，得产物B200克，产率：72.5％。
在500mL三口烧瓶中加入26.5克无水碳酸钠，用75mL的水溶解。待其溶解后，加入75.6克的B、17.5克的盐酸羟胺和300mL的无水乙醇，在85℃左右反应20h。反应完毕后，过滤，将所得滤液抽干，得产物C67.4克，产率为：80.0％。

Claims (1)

1.结构式为
式中X＝Boc-t的N-羟基脒类化合物的制备方法，将2位、4位或6位的卤代吡啶化腈在无水乙醇中与无水哌嗪作用生成含1位哌嗪基的吡啶化腈类化合物；然后利用二碳酸二叔丁酯进行单氨基保护；再与盐酸羟胺、碱金属的碳酸盐反应生成N-羟基脒类化合物。
CNB021392110A 2002-10-28 2002-10-28 一种n-羟基脒类化合物的制备方法 Expired - Fee Related CN1173952C (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7622486B2 (en) 2004-09-23 2009-11-24 Reddy Us Therapeutics, Inc. Pyridine compounds, process for their preparation and compositions containing them

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7622486B2 (en) 2004-09-23 2009-11-24 Reddy Us Therapeutics, Inc. Pyridine compounds, process for their preparation and compositions containing them

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