CN1059437C - 氰基亚氨基－１，３－噻唑烷类化合物的制备方法 - Google Patents

氰基亚氨基－１，３－噻唑烷类化合物的制备方法 Download PDF

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CN1059437C
CN1059437C CN95115073A CN95115073A CN1059437C CN 1059437 C CN1059437 C CN 1059437C CN 95115073 A CN95115073 A CN 95115073A CN 95115073 A CN95115073 A CN 95115073A CN 1059437 C CN1059437 C CN 1059437C
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cyanoimino
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butyl
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R·兰茨施
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/18—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/31—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/32—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to an acyclic carbon atom of the carbon skeleton

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
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Abstract

本发明涉及氰基亚氨基-1，3-噻唑烷的制备方法，该方法是：使式(Ⅰ)的半胱胺盐和式(Ⅱ)的N-氰基亚氨碳酸二烷基酯反应，得到式(Ⅲ)的中间体，然后在pH8-9.5将中间体环化，得到式(Ⅳ)的氰基亚氨基-1，3-噻唑烷。

Description

氰基亚氨基－１，３－噻唑烷类化合物的制备方法
本发明涉及氰基亚氨基-1，3-噻唑烷的新的制备方法。
已知，如果将N-氰基二硫代碳酸二甲酯与半胱胺在乙醇中加热回流，可以得到氰基亚氨基-1，3-噻唑烷(参见Archivder Pharmazie 305，731(1972))。但是，该方法的缺点是要消去2当量的甲基硫醇。由于甲基硫醇是一种严重的呼吸系统毒物，必需有附加的安全措施，而且必须将其焚毁或者通过用次氯酸钠水溶液或过氧化氢氧化将其破坏，因此由于毒理学和环境方面的原因，用这种途径进行工业化生产是非常昂贵的。
又已知，如果将N-氰基亚氨碳酸二甲酯与半胱胺在氢氧化钠水溶液中、于pH 10-11长时间搅拌，可以得到氰基亚氨基-1，3-噻唑烷(参见Org.Prep.Procedure Int.23，(6)，721-728(1991))。然而，如此得到的产物熔点(m.p.168-170℃)与纯的氰基亚氨基-1，3-噻唑烷的熔点(m.p.154-156℃)有相当大的不同，因为前者可能被副产物污染了。
因此，进一步纯化将会更加降低产率(为48％)，以致于该方法也不适合于工业化生产。
现在出人意料地发现，如果以下列方法进行反应，可以非常好的产率和纯度得到氰基亚氨基-1，3-噻唑烷该方法是在稀释剂存在下，对反应物半胱胺盐(I)或N-氰基亚氨碳酸二烷基酯(II)而言至少2倍当量碱存在下，以及如果需要的话在保护气体气氛存在下，将式(I)的半胱胺盐
Figure C9511507300051
其中X表示酸根，与式(II)的N-氰基亚氨碳酸二烷基酯反应：
Figure C9511507300052
其中R1和R2表示甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，得到式(III)的中间体产物：
Figure C9511507300053
其中A(+)表示相当的金属离子或铵离子，然后将其在pH 8-9.5环化，得到式(IV)的氰基亚氨基-1，3-噻唑烷，
Figure C9511507300061
应该认为，通过本发明方法得到高纯度和高产率的氰基亚氨基-1，3-噻唑烷是非常出人意料的，因为已知道，N-氰基亚氨碳酸二甲酯与半胱胺于0℃在水中反应，会形成N-氰基-N′-(2-巯基乙基)-氨基甲亚胺酸(carbamimidate)甲酯或由其形成的二硫化物[参见Chemistry and Industry 1983，349-352；Org.Prep.Procedures Int.23，(6)721-728(1991)]。因此该新方法表明比现有技术有实质性的改进。
对于本发明方法，优选使用式(I)化合物，其中X表示酸根，例如氢卤酸根、乙酸根、硫酸根或硫酸氢根。
对于本发明方法，还优选使用式(II)化合物，其中R1和R2表示甲基或乙基。
在本发明方法中形成的式(III)中间体，如果A表示钠、钾或铵离子，则该中间体是优选的。
例如，可以用下列反应流程描述使用盐酸半胱胺、氢氧化钠溶液和N-氰基亚氨碳酸二甲酯进行的本发明方法。
第一阶段
Figure C9511507300071
第二阶段
Figure C9511507300072
在本发明方法中用作原料的式(I)的半胱胺盐和式(II)的N-氰基亚氨碳酸二烷基酯类化合物是有机化学领域公知的化合物。
本发明方法优选在稀释剂存在下进行。合适的稀释剂是所有的在反应条件下是惰性的常用溶剂。这些稀释剂包括例如水；醇类如甲醇、乙醇、丙醇或丁醇；腈类如乙腈、丁腈或异丁腈；或者醚类如二甲氧基乙烷、甲基叔丁基醚或TAME。特别优选在水中或者水/醇混合物中进行反应。
当进行本发明的方法时，反应温度可以在较宽的范围内变化。该方法通常在0℃-100℃温度下、优选在0℃-70℃温度下进行。
通过下述方式进行本发明方法：首先将适合的式(I)的半胱胺盐掺入碱与上述一种溶剂的混合物中，然后在所述温度下分批加入一种式(II)的N-氰基亚氨碳酸二烷基酯。然后加入无机酸例如硫酸或盐酸(如果需要也可以以气体的形式使用)，使其在pH 8-9.5环化。也可以反过来加料：首先在溶剂中加入N-氰基亚氨碳酸二烷基酯，然后计量加入半胱胺盐与至少2当量碱的溶液。在此方法中，不希望的二硫化物的形成特别少。反应混合物可以通过常规方法处理(参见制备实施例)。
合适的碱是碱金属氢氧化物如氢氧化钠和氢氧化钾；碱土金属氢氧化物如氢氧化钙；以及碱金属碳酸盐和碱金属醇盐如碳酸钠、碳酸钾、甲醇钠、甲醇钾、乙醇钠和乙醇钾，这些碱过量使用。
如果需要，本发明方法在惰性气体存在下进行。本文中，合适的惰性气体是氮，以及实际上还有所有的稀有气体，特别是氩。
通过本发明方法制备的氰基亚氨基-1，3-噻唑烷可以用作生产杀虫剂的原料(参见EP-A 235 725)。
通过下列实施例说明本发明。
实施例1
首先在氮气氛下加入17.8g(0.2mol)45％浓度的氢氧化钠溶液并用30ml水稀释，然后加入11.6g(0.1mol)盐酸半胱胺。在30-35℃搅拌该溶液15分钟，然后冷却至0℃。
然后分批加入11.4g(0.1mol)N-氰基亚氨碳酸二甲酯，并将该混合物在0-5℃搅拌2.5小时。pH为12.7。使温度升至室温，加入盐酸将pH调至9.5，然后将混合物加热至40℃，并将pH调至9.0。将反应混合物搅拌8小时，调节pH至6.8，吸滤出固体并干燥。
得到10.9 g氰基亚氨基-1，3-噻唑烷，熔点为154℃。根据HPLC，其纯度达95.8％。二硫化物的含量为1.9％；相应于理论产率的82.1％。

Claims (3)

1.制备氰基亚氨基-1，3-噻唑烷的方法，其特征在于：在稀释剂存在下，对反应物半胱胺盐(I)或N-氰基亚氨碳酸二烷基酯(II)而言至少2倍当量碱存在下，以及如果需要的话在保护气体气氛存在下，将式(I)的半胱胺盐
Figure C9511507300021
其中X表示酸根，与式(II)的N-氰基亚氨碳酸二烷基酯反应：
Figure C9511507300022
其中R1和R2表示甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基或叔丁基，得到式(III)的中间体产物：
Figure C9511507300023
其中A(+)表示相当的金属离子或铵离子，然后将其在pH 8-9.5环化，得到式(IV)的氰基亚氨基-1，3-噻唑烷。
Figure C9511507300031
2.按照权利要求1的方法，其特征在于：使用式(I)化合物，其中X表示选自氢卤酸根、乙酸根、硫酸根或硫酸氢根的酸根。
3.按照权利要求2的方法，其特征在于：使用式(II)化合物，其中
R1和R2表示甲基或乙基。
CN95115073A 1994-08-04 1995-08-04 氰基亚氨基－１，３－噻唑烷类化合物的制备方法 Expired - Lifetime CN1059437C (zh)

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CN102408391A (zh) * 2011-12-15 2012-04-11 江苏常隆化工有限公司 噻唑烷的生产方法

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DE19926233C1 (de) * 1999-06-10 2000-10-19 Probiodrug Ges Fuer Arzneim Verfahren zur Herstellung von Thiazolidin
US6858737B2 (en) * 2001-12-28 2005-02-22 Nippon Carbide Kogyo Kabushiki Kaisha Process for producing 2-cyanoimino-1,3-thiazolidine
WO2003057680A1 (fr) * 2001-12-28 2003-07-17 Nippon Carbide Kogyo Kabushiki Kaisha Procede de production de 2-cyanoimino-1,3-thiazolidine
US20120295977A1 (en) * 2003-05-23 2012-11-22 Ott David M Organosulfur prodrugs for the prevention and treatment of infectious diseases
EP2042493A1 (de) * 2007-09-14 2009-04-01 Bayer CropScience AG Verfahren zum Herstellen von Cyanimino-1,3-thiazolidinen
CA2714027A1 (en) * 2008-02-01 2009-09-17 Hikal Limited A process for the preparation of 2-cyanoimino-1,3-thiazolidine
JP2014525422A (ja) * 2011-09-02 2014-09-29 バイエル・インテレクチユアル・プロパテイー・ゲー・エム・ベー・ハー ［３−［（６−クロロ−３−ピリジニル）メチル］−２−チアゾリジニリデン］シアナミドを製造する方法

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JPH0717621B2 (ja) 1986-03-07 1995-03-01 日本バイエルアグロケム株式会社 新規ヘテロ環式化合物

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102408391A (zh) * 2011-12-15 2012-04-11 江苏常隆化工有限公司 噻唑烷的生产方法
CN102408391B (zh) * 2011-12-15 2014-08-13 江苏常隆化工有限公司 噻唑烷的生产方法

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ATE159013T1 (de) 1997-10-15
DE59500764D1 (de) 1997-11-13
JP3810108B2 (ja) 2006-08-16
US5574165A (en) 1996-11-12
KR100346800B1 (ko) 2002-11-04
JPH0859640A (ja) 1996-03-05
TW319768B (zh) 1997-11-11
HU9502298D0 (en) 1995-09-28
EP0695744B1 (de) 1997-10-08
HUT72758A (en) 1996-05-28
KR960007576A (ko) 1996-03-22
CN1128759A (zh) 1996-08-14

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