CN108164560B - 草铵膦的制备方法 - Google Patents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
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Abstract
一种草铵膦的制备方法,首先利用简洁经济的办法引入硝基,然后在温和的条件下对硝基进行还原从而引进氨基作为关键步骤,避免了使用其他昂贵的氨基酸衍生物或者其他有毒含氮的化合物来引入氨基的办法,同时还免去了反应过程中对氨基的保护和脱保护过程,整个反应历程简捷,条件温和,使用原料简单易得,操作简便,原子经济性好,极其适于工业化生产。
Description
技术领域
本发明属于有机合成和农药合成领域,具体来说,涉及一种除草剂草铵膦新的制备方法。
背景技术
草铵膦是一种具有部分内吸作用的高效、低毒、非选择性(灭杀性)触杀型有机磷类除草剂,于上个世纪80年代由德国Hoechst公司最先开发生产。除了具有除草活性外,还具有杀虫杀菌活性,并且可以与杀虫剂等混配,达到同时防治的效果。该除草剂具有高效的除草活性,几乎能防除各种杂草,同时其低毒、易降解、可用水作基剂、不易产生耐药性等特点,使其使用安全方便。目前草铵膦的用量仅次于草甘膦,是世界第二大转基因作物的除草剂。而且随着杂草对草甘膦耐药性的不断增加,草铵膦应用前景更加广泛。
草铵膦的合成方法有发酵法和化学合成法。前者是用双丙氨酰磷经微生物发酵生产。化学合成方法主要以三氯化磷或亚膦酸酯为起始原料,经过一定的反应过程合成膦酸酯,然后与某些氨基衍生物发生反应。
目前比较经典的合成草铵膦的方法是盖布瑞尔-丙二酸二乙酯合成法(WO79/00405,CN185054A,US6359162)。
该法反应条件比较温和,不需要高温高压,但反应历程较长,并且需要较贵且危险的试剂,如金属钠、液溴及二溴乙烷,导致该路线不经济。此外,产率也比较低,总收率仅为10%。反应过程中过量的醇钠易于膦化物发生副反应。
另外,斯垂克-泽林斯基法是研究最为深入的方法(US4264532,CN1267305A,CN10258489A)。目前已经实现的工业化路线都是围绕着这种方法进行改进而成。
该法采用比较成熟的工艺,收率为30%左右,且反应条件要求不高,易于应用于生产。但是,KCN为剧毒物质,对环境不友好。其中的丙烯醛或丙烯腈的Micheal加成步骤以及α-氨基酸的合成步骤为关键步骤。由于丙烯醛和丙烯腈聚合活性非常高、且毒性非常大,在生产和后处理过程中给环境和生产安全带来巨大的不利因素。另外氨基酸的形成过程经常使用高毒或昂贵的试剂,进一步加剧了整个反应过程的不安全性和非经济性。
在其他的方法中,如阿布佐夫合成法,该法以亚膦酸酯衍生物为起始原料,反应历程简捷,且反应条件要求不高,但氨基需要用较为昂贵的三氟甲酰基,不经济。高压催化合成法,顾名思义,该法需要较大的压力,导致对设备的强度要求较高,不适于工业化生产。同时,该法用到剧毒气体CO,及较贵的氢气。
此外,还有从α-溴-γ-内丁酯和邻苯二甲酰亚胺出发合成草铵膦的途径(俞传明.农药,2001,40(4),15)。
该法尽管反应条件要求不高,但是原料邻苯二甲酰亚胺较贵,原子经济性差,收率也不高。
发明内容
本发明鉴于之前从α-溴-γ-丁内酯出发合成草铵膦路线中需要使用昂贵的邻苯二甲酰亚胺,提出料一条合成草铵膦的新方法。首先利用α-溴-γ-丁内酯和亚硝酸钠反应,经过对酯基的断裂,膦酸酯部分的形成,然后在含氟添加剂的作用下中用金属和酸的体系对硝基进行还原制备草铵膦。该方法利用在温和的条件下对硝基进行还原来引进氨基,避免了使用其他昂贵的氨基酸衍生物或者其他含氨基的化合物来引入氨基,同时还免去了反应过程中对氨基的保护和脱保护过程,反应历程简捷,条件温和,使用原料简单易得,原材料安全性好,路线具有极佳的原子经济性,操作简便,非常适于工业化生产。
本发明是一种制备草铵膦的新方法。
该方法主要包括以下步骤。
步骤1:将α-溴-γ-丁内酯2与亚硝酸钠进行反应,得到α-硝基-γ-丁内酯3;
步骤2:将α-硝基-γ-丁内酯3与氢溴酸作用在溶剂中开环,生成化合物4;
步骤3:将化合物4与甲基亚膦酸酯反应,得到化合物5;
步骤4:在含氟添加剂的存在下,使用普通金属和酸的体系对化合物5进行还原,得到化合物6;
步骤5:最后,将化合物6和氨水反应成盐,得到目标化合物1。
具体实施方式:
下面对本发明的具体实施方式进行说明,应该说明的是,下述说明仅是为了解释本发明,并不对其内容进行限定。
实施例1:
步骤1:将α-溴-γ-丁内酯2(16.5g,0.1mmol)和亚硝酸钠(13.8g,0.2mmol)加入装有DMF(20mL)的100mL反应瓶中,在室温下搅拌30min反应完全。结束后加入50mL乙酸乙酯稀释,再用水(80mL×3)洗涤除去DMF,将有机相浓缩得到α-硝基-γ-丁内酯3直接用于下一步反应10.2g,产率78%。
步骤2:向500mL反应瓶中依次加入化合物3(39.3g,0.3mmol),45%氢溴酸(75mL),甲醇(150mL),升温至75℃回流4h后降至室温,并搅拌过夜。反应结束后减压除掉溶剂,将得到的粗产物溶于乙酸乙酯(150mL),依次用饱和碳酸氢钠溶液洗涤,饱和食盐水(150mL)洗涤,无水硫酸镁干燥后浓缩得到目标化合物4,58.3g,纯度为97%,产率86%。
步骤3:向化合物4(0.45g,2mmol)的甲苯(30mL)溶液中加入甲基亚膦酸二乙酯(5mL),接着将混合物加热至110℃反应15h。结束后冷却至室温,经分离纯化后得到目标化合物5,0.33g,产率为66%。
步骤4:采用一锅法进行反应。依次将化合物5(0.76g,3mmol),锌粉(0.98g,15mmol),HFIP(6mL),2N盐酸溶液(30mL)加入反应瓶100mL中,在室温下反应30min。结束后加入50mL乙酸乙酯稀释。然后过滤得到粗品,再经重结晶得到目标化合物6,0.47g,纯度98%,产率87%。
步骤5:向化合物6(0.36g,2mmol)的丙酮(15mL)溶液中加入5mL氨水溶液。接着将混合物在室温下搅拌30min。反应结束后,浓缩至干后经重结晶得到目标化合物1,0.4g,产率95%。
Claims (7)
1.一种制备草铵膦1的方法,其特征在于,步骤如下:
(1)以α-溴-γ-丁内酯2和亚硝酸钠为原料,在反应溶剂中,在20-100℃下进行硝基化反应,得到α-硝基-γ-丁内酯3,反应过程用TLC判断反应终点,所述α-溴-γ-丁内酯2与亚硝酸钠的摩尔配比为1∶1.0-5.0;
(2)将步骤(1)制得的α-硝基-γ-丁内酯3、氢溴酸和溶剂在室温下搅拌10-24h,生成硝基化合物4,所述α-硝基-γ-丁内酯3与氢溴酸的摩尔配比为1∶1.0-3.0;
(3)将步骤(2)得到的化合物4与甲基亚膦酸酯在溶剂中,在50-150℃下反应2-10h得到甲基亚膦酸酯硝基化合物5,化合物4与甲基亚膦酸酯的配比为1∶1.5-5;
(4)将步骤(3)所得化合物5在金属与盐酸体系下,加入添加剂,15-50℃下反应15min-3h得到α-氨基酸6;化合物5、金属、盐酸、添加剂的摩尔配比为1∶1-5∶5-20∶0.5-10;
(5)最后,将化合物6和氨水在室温下搅拌30min,得到目标化合物1
。
2.如权利要求1所述的方法,其特征在于步骤1所用溶剂为去离子水、THF、二氧六环、DMF中的一种或几种的混合物。
3.如权利要求1所述的方法,其特征在于步骤2所用溶剂为甲醇、乙醇、异丙醇、正丁醇、乙二醇的一种或几种的混合物。
4.如权利要求1所述的方法,其特征在于步骤3所用溶剂为二氧六环、甲苯、二甲苯中的一种或几种的混合物。
5.如权利要求1所述的方法,其特征在于步骤4中的金属为锌粉、铁粉、锰粉、镍的一种或几种的混合物。
6.如权利要求1所述的方法,其特征在于步骤4中所用盐酸的浓度为1N-6N。
7.如权利要求1所述的方法,其特征在于步骤4中添加剂为七氟醚、六氟异丙醇、三氟甲苯的一种或几种的混合物。
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US5374736A (en) * | 1988-05-27 | 1994-12-20 | Hoechst Aktiengesellschaft | L-4-(phosphinylethyl)-1,3-oxazolidin-5-one derivatives as intermediates for synthesis of phosphorus-containing L-amino acids |
US5442088A (en) * | 1991-04-06 | 1995-08-15 | Hoechst Aktiengesellschaft | Process for the preparation of phosphorus-containing L-amino acids, their derivatives and intermediates for this process |
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US5442088A (en) * | 1991-04-06 | 1995-08-15 | Hoechst Aktiengesellschaft | Process for the preparation of phosphorus-containing L-amino acids, their derivatives and intermediates for this process |
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