CN105324365A - 用于制备n-氰基-s-[1-(吡啶-3-基)乙基]-s-甲基硫亚胺的改善方法 - Google Patents

用于制备n-氰基-s-[1-(吡啶-3-基)乙基]-s-甲基硫亚胺的改善方法 Download PDF

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CN105324365A
CN105324365A CN201380064126.9A CN201380064126A CN105324365A CN 105324365 A CN105324365 A CN 105324365A CN 201380064126 A CN201380064126 A CN 201380064126A CN 105324365 A CN105324365 A CN 105324365A
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hypochlorite
cyanamide
sulfide
aforementioned
ethyl
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M·A·冈萨雷斯
C·米斯
陈晓云
F·丹
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Corteva Agriscience LLC
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Dow AgroSciences LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C07D213/34—Sulfur atoms to which a second hetero atom is attached

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

由相应的硫化物、氨腈和次氯酸盐，通过在腈溶剂存在下，将硫化物添加至氨腈和次氯酸盐的溶液，同时保持pH为约8至约12，有效地和高收率地制备氰基取代的硫亚胺。

Description

用于制备N-氰基-S-[1-(吡啶-3-基)乙基]-S-甲基硫亚胺的改善方法
相关申请的交叉引用
本申请要求2012年12月11日提交的美国临时申请序列号61/735573的权益以及2012年12月11日提交的美国临时申请序列号61/735612的权益，将其全部内容并入本申请作为参考。
发明背景
本发明关注制备某些氰基取代的硫亚胺的改善方法。
氰基取代的硫亚胺是用于制备某些杀虫性亚磺酰亚胺(sulfoximines)的有用中间体，例如参见美国专利7,678,920B2和7,687,634B2。美国专利7,868,027B2描述了通过在合适有机溶剂存在下相应硫化物与氨腈和次氯酸盐溶液的反应制备取代的硫亚胺。尽管美国专利7,868,027B2的次氯酸盐方法优于美国专利7,678,920B2和7,687,634B2中描述的二乙酸碘苯方法，但是其受困于显著水平的源自硫化物原料的竞争性副产物。有利的是，由相应硫化物通过次氯酸盐路线高效地和高收率地制备取代的硫亚胺。
发明概述
因此，本发明关注制备某些取代的硫亚胺的方法，所述取代的硫亚胺具有通式(I)
其中X代表卤素、C1-C4烷基或C1-C4卤代烷基，
所述方法包括在腈溶剂存在下，在约-20℃至约10℃的温度，将式(II)的硫化物与氨腈和次氯酸盐的水溶液混合，同时保持pH为约8至约12，
其中X如之前所定义。
发明详述
在本文全文，所有温度以℃给出，所有百分数为重量百分数，除非另外说明。
本申请使用的术语“烷基”以及其派生术语如“卤代烷基”在其范围内包括直链、支链和环状部分。因此，通常的烷基为甲基、乙基、1-甲基-乙基、丙基、1,1-二甲基乙基，以及环丙基。术语“卤代烷基”包括取代有一个至最大可能数量的卤素原子(包括卤素的所有组合)的烷基。术语“卤素”或“卤代”包括氟、氯、溴和碘，其中优选氟。
式II的硫化物原料或者其制备方法已经披露于美国专利7,678,920B2和7,687,634B2中。最优选的硫化物是3-[1-(甲硫基)乙基]-6-(三氟甲基)吡啶(I,X＝CF3)。
氨腈可以以固体使用或者优选以水溶液使用。通常优选使用50wt％的氨腈水溶液。要求化学计量量的氨腈，但是优选使用约1.5至约3.0摩尔当量，基于硫化物的量。氨腈也优选相对于次氯酸盐过量。通常使用约1.01至约3.0摩尔当量的氨腈，基于次氯酸盐的量。
对于次氯酸盐，其是指次氯酸的金属盐的水溶液。该金属盐可以是第一族碱金属盐或第二族碱土金属盐。优选的次氯酸盐为次氯酸钠或次氯酸钙。次氯酸盐水溶液通常含有约5％至约20％次氯酸盐，最优选约10％至约13％次氯酸盐。理论上要求相对于氨腈的化学计量量的次氯酸盐，但是优选使用约0.33至约0.99摩尔当量的次氯酸盐，基于氨腈的量。次氯酸盐也优选相对于硫化物过量。通常使用约1.4至约2.7摩尔当量的次氯酸盐，基于硫化物的量。
在腈溶剂优选乙腈存在下进行该反应。腈溶剂可以在与硫化物混合之前，加入到次氯酸盐和氨腈的水性混合物中，在这种情形中硫化物可以纯地添加，或者溶解在另外的腈溶剂中。反之，可以将溶解在腈溶剂中的硫化物添加至次氯酸盐和氨腈的水性混合物中。腈溶剂通常占全部反应混合物的约25wt％至约75wt％。
应该低于约10℃进行该反应，以阻止不期望的副产物形成和降低收率。尽管较低温度是有益的，由于次氯酸盐中存在水以及盐的冷冻和/或沉淀的伴随可能，最实用的反应温度可以为约-20℃至约5℃。优选范围为约-15℃至约-5℃。
为了最小化不期望的副产物形成和最大化收率，应该在次氯酸盐/氨腈已经混合之后，尽可能快地使次氯酸盐/氨腈混合物与硫化物混合。
对于次氯酸盐-氨腈混合物，将pH控制为约8至约12，最优选约9至约11。这可以通过添加碱如氢氧化钠的水溶液或者通过使用缓冲剂例如K3PO4来进行，任一种可以在反应之前或者在反应过程中或者两者添加。
除了pH控制，重要的是硫化物与次氯酸盐和氨腈的混合物反应，其中氨腈相对于次氯酸盐过量。这通常如下完成：将次氯酸盐和氨腈优选在乙腈中预混，接着将所得混合物与硫化物任选也在乙腈中混合。备选地，次氯酸盐和硫化物可以同时添加到氨腈中，条件是在开始添加硫化物之前，将一部分次氯酸盐加入到所述氨腈中，在整个同时添加的过程中保持初始过量的次氯酸盐。在添加硫化物之前添加到氨腈的次氯酸盐的部分可以为5-95％，优选为10-30％。
如本领域技术人员所理解的，反应器设计对于获得最优收率是重要的。反应器需要设计为实现最优温度控制、停留时间控制和混合。潜在有用的反应器设计的实例包括各种组合和构造的CSTR(连续搅拌罐反应器)、平推流反应器和静态混合器，以及有效的热移除。
在反应结束时，在进行下一步之前，通常用NaHSO3或SO2来还原过量氧化剂。将水相与有机硫亚胺相分离。硫亚胺的有机溶液可以直接在后继氧化为杀虫性亚磺酰亚胺中直接使用，或者硫亚胺可以通过常规技术来分离和纯化。
给出以下实施例来说明本发明。
实施例
在具有手动和iControl软件控制和数据收集的MettlerToledoEasyMaxTM反应器装置中进行实验。EasyMax装置采用150毫升(mL)玻璃反应器烧瓶，其装配有电子顶置式搅拌(4-桨叶下倾式HC-22搅拌器)、热电偶套管、氮气垫和MettlerToledo计量单元(具有Teflon进样管的玻璃注射泵)。
HPLC条件如下：
·柱:ZorbaxEclipseXDB-Phenyl150x4.6(5-微米)；注射体积＝10微升
·检测器:UV，260nm
·流速:1.25mL/min
·洗脱剂:85:1590％水/10％MeOH至100％乙腈，15分钟；60:40，6分钟；85:15，剩余9分钟(总计30分钟运行时间)；或者
·洗脱剂:储液A:90％水,10％乙腈,储液B:100％乙腈。85/15A/B保持15分钟，然后在5min升高到60/40A/B，然后在60/40A/B保持6分钟，然后在4分钟升高到85/15A/B。
定量分析:
·样品制备:0.2mL反应混合物(4-5滴)至1.5mL乙腈/水(50:50)中；
定量分析:
样品制备:将约30mg精确称量的内标(苯邻二甲酰亚胺)与约200mg精确称量的反应混合物(4-5滴)加入至5.0mL乙腈和5滴水。然后将6滴该混合物加入到1.0mL乙腈/水(50:50)中，注入至5微米环管(在ChemStation软件中使用硫亚胺的标准等级样品产生校准曲线/响应因子)。
实施例1制备(1-{6-[三氟甲基]吡啶-3-基}乙基)-(甲基)-λ 4 -硫亚氨腈 (sulfanylidenecyanamide)
反应器投入41.0g乙腈(998.8mmol)和1.0g40％K3PO4溶液(2.4mmol)。开始搅拌(500rpm)，反应器冷却至-5.0℃，接着添加6.3g50％氨腈溶液(75.0mmol)，接着开始7小时(hr)滴加36.0mL13％漂白剂(74.8mmol次氯酸盐)。大约10％(42分钟(min))漂白剂添加，同时滴加10.0mL的93％纯3-[1-(甲硫基)乙基]-6-(三氟甲基)吡啶(51.6mmol)7hr(在吡啶硫化物加入前，漂白剂添加进行约42min)。在完成吡啶硫化物添加之后，使反应混合约30min，之后温热至环境温度，在该温度分离各相。通过HPLC分析有机相和水相两者。定量分析(如上所述)得到分析样品的重量百分数，其是使用分离的有机相的总重量反向外推的，得到94.3％硫亚胺收率。
实施例2制备(1-{6-[三氟甲基]吡啶-3-基}-乙基)(甲基)-λ 4 -硫亚氨腈
反应器投入38.0g漂白剂(66.4mmol)和21.0g乙腈(511.6mmol)。开始搅拌(500rpm)，将反应器冷却至-5.0℃，接着在大约1分钟内经由移液管添加6.3g50％氨腈溶液(75.0mmol)，这导致温度升高。在温度回转为-5.0℃之后，开始6hr滴加5.0mL93％3-[1-(甲硫基)乙基]-6-(三氟甲基)吡啶(25.8mmol)。在6hr内使用滴加总计1.51g25％NaOH(9.4mmol)来手动控制pH，保持pH为10.3-10.6。在完成吡啶硫化物添加之后，使反应混合约30min，之后温热至环境温度，在该温度分离各相。通过HPLC分析有机相和水相两者。定量分析(如上所述)得到分析样品的重量百分数，其是使用分离的有机相的总重量反向外推的，得到近乎定量(nearquantitative)的硫亚胺收率。

Claims (8)

1.制备式(I)的硫亚胺的方法，
其中X代表卤素、C1-C4烷基或C1-C4卤代烷基，
所述方法包括在腈溶剂存在下，在约-20℃至约10℃的温度，将式(II)的硫化物与氨腈和次氯酸盐的水溶液混合，同时保持pH为约8至约12，
其中X如之前所定义。
2.权利要求1的方法，其中X代表CF3。
3.权利要求1或2的方法，其中所述腈溶剂为乙腈。
4.前述权利要求中任一项的方法，其中所述温度为约-15℃至约-5℃。
5.前述权利要求中任一项的方法，其中pH为约9至约11。
6.前述权利要求中任一项的方法，其中所述次氯酸盐和所述硫化物同时加入到所述氨腈，条件是在开始添加硫化物之前，约10-30％的所述次氯酸盐加入到所述氨腈中，在整个同时添加的过程中保持相对于硫化物初始过量的次氯酸盐。
7.前述权利要求中任一项的方法，其中10％至约13％次氯酸钠用作所述次氯酸盐。
8.前述权利要求中任一项的方法，其中使用氢氧化钠的水溶液来保持pH。
CN201380064126.9A 2012-12-11 2013-12-10 用于制备n-氰基-s-[1-(吡啶-3-基)乙基]-s-甲基硫亚胺的改善方法 Pending CN105324365A (zh)

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US201261735573P 2012-12-11 2012-12-11
US201261735612P 2012-12-11 2012-12-11
US61/735,573 2012-12-11
US61/735,612 2012-12-11
PCT/US2013/074006 WO2014093276A1 (en) 2012-12-11 2013-12-10 Improved process for the preparation of|n-cyano-s-[1 -(pyridin-3-yl)ethyl]-s-methylsulfilimines

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