CN107857778B - 含膦酰基的α-氨基腈的制备方法 - Google Patents
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- 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
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Abstract
本发明公开了一种含膦酰基的α‑氨基腈的制备方法，该方法采用芳亚甲基氨基乙腈与乙烯基甲膦酸酯在有机溶剂中加成，然后在水中脱去保护基，得到含膦酰基的α‑氨基腈。本发明不使用高毒、恶臭的原料，并且工艺简单、原料易得、条件温和，适合工业化生产。
Description
技术领域
本发明涉及一种含膦酰基的α-氨基腈的制备方法，属于有机合成化学技术领域。
背景技术
2-氨基-4-(烷氧基甲膦酰基)丁腈又称3-氨基-3-氰基丙基甲膦酸烷基酯，是一种典型的含膦酰基的α-氨基腈，主要用于合成农药草铵膦。
草铵膦(glufosinate)，是一种广谱触杀型除草剂，具有部分内吸作用的高效、低毒、非选择性。因杀草活性高，药效迅速，广泛用于油菜、玉米、棉花、大豆、水稻和果园的除草，是目前转基因抗性作物中比较理想的除草剂。
有关草铵膦的化学合成方法文献报道很多，特别是近年来，国内对草铵膦原药的合成研究、应用建设形成高潮，出现许多新合成方法或旧工艺技术改进。其中，利用Strecker反应制备含有甲膦酰基的α-氨基腈，然后水解得到草铵膦的工艺方法尤其比较成熟，得到普遍应用(专利CN103288874B)。该工艺方法如专利CN1261442C(WO1999/009039)报道，采用丙烯醛与甲基亚膦酸二乙酯在乙醇中反应，生成甲膦酰基丙缩醛，然后在氨水或氯化铵中与氰化物加成，制备4-(乙氧基甲膦酰基)-2-氨基丁腈，最后酸性水解，氨水中和得到草铵膦。专利CN103288874、CN104497039、WO2015/173146在此基础上进行改进，提高工艺收率。虽然该工艺方法具有工艺步骤短、反应条件温和、原料廉价易得的优点，但需要使用剧毒、恶臭的原料氰化物、丙烯醛，在安全、环保方面受到限制。
为避免使用剧毒、恶臭原料，专利EP0292918公开一种采用乙烯基甲膦酸乙酯与苯亚甲基甘氨酸异丙酯加成，然后酸性水解、氨水中和的方法。专利CN105131032采用类似工艺路线，在手性催化剂催化下，先合成一种S型苯亚甲基氨基甲膦酰基丁酸酯，然后在酸催化下水解脱苯亚甲基，再用氨水中和成盐，得到L型草铵膦。该方法操作步骤少、反应条件温和，得到高活性的L型草铵膦。但该工艺需要较低的反应温度，手性催化剂也比较昂贵，生产成本高，工业化生产具有难度，而且水解后副产物太多，不利于清洁生产。
发明内容
为克服含膦酰基的α-氨基腈制备中存在的生产成本高、三废污染大的缺陷，本发明的目的是提供一种高收率、低污染、制备方便的含膦酰基的α-氨基腈的制备方法。
本发明采用芳亚甲基氨基乙腈与乙烯基甲膦酸烷基酯加成，然后脱去芳亚甲基得到含膦酰基的α-氨基腈类中间体2-氨基-4-(烷氧基甲膦酰基)丁腈。包括如下步骤：
(1)以式(Ⅱ)所示的芳亚甲基氨基乙腈与(Ⅲ)所示的乙烯基甲膦酸烷基酯类化合物为原料，在有机溶剂中进行反应，得到式(Ⅳ)所示的含膦酰基的α-氨基腈衍生物；
其中，R为C1～C2的烷基，Ar为取代或未取代的苯基、取代苯基或二苯基；
(2)将步骤(1)制得的式(Ⅳ)所示的含膦酰基的α-氨基腈衍生物与水反应，脱去芳亚甲基保护基；
则可得到含膦酰基的α-氨基腈(Ⅰ)。
在步骤(1)中，所述的有机溶剂为甲醇、乙醇、异丙醇、乙醚、丁醚、四氢呋喃、二氧戊环、二氯甲烷、三氯甲烷、二氯乙烷、甲苯、二甲苯。
在步骤(1)中，芳亚甲基氨基乙腈、乙烯基甲膦酸烷基酯类化合物是等分子发生化学反应，二者参与反应的物质的量是相等的，但因乙烯基甲膦酸烷基酯类化合物比较贵重，故芳亚甲基氨基乙腈稍微过量。为使用反应顺利进行，加入数倍量的有机溶剂。因此，在本发明步骤(1)中，所述的芳亚甲基氨基乙腈、乙烯基甲膦酸烷基酯类化合物和有机溶剂的物质的量比是1:(0.8～1.0):(2～5)。
芳亚甲基氨基乙腈和乙烯基甲膦酸烷基酯类化合物之间的反应比较迅速，通常在较短的时间内就能充分完成。使用高效液相色谱(HPLC)或简单的薄层色谱法(TLC)跟踪反应，以检测不到乙烯基甲膦酸烷基酯类化合物为终点。所以，在步骤(1)中，所述在有机溶剂中进行反应的反应时间为4～24小时。
加热是促进化学反应常用的、有效的方法。在步骤(1)中，所述在有机溶剂中进行反应的反应温度为10～150℃。
含膦酰基的α-氨基腈衍生物极易与水反应，脱去保护基团，因此，在步骤(2)中，所述的含膦酰基的α-氨基腈衍生物与水反应，α-氨基腈衍生物与水的物质的量比是1:(2.0～20.0)，反应温度是50～150℃，反应时间是4～24小时。
与现有技术相比，本发明具有如下优点：
(1)虽然使用氨基乙腈也可进行反应，但由于氨基乙腈中氨基上氢原子比较活泼，与乙烯基甲膦酸烷基酯加成反应时需要保护，因此，本领域技术人员通常选择醛或酮等将氨基转化为亚胺(Shiff碱)进行保护，待反应后然后水解脱去醛或酮，而本发明通过使用一种分子内含有氨基和氰基的原料芳亚甲基氨基乙腈，因此不需要使用氰化物、丙烯醛等剧毒、恶臭的原料。
(2)本发明工艺简单、原料易得、条件温和，适合工业化生产，从所涉及的化学反应可看出，该方法基本没有副产物，原子利用率高，符合清洁生产的要求。
具体实施方式
通过下面的实施例，对本发明作进一步的描述。
实施例1
在250ml反应瓶中，加入苯亚甲基氨基乙腈15.0g(0.104mol)和甲苯25ml，搅拌混合均匀后，加甲醇钠1g。升温至48～52℃，滴加乙烯基甲膦酸乙酯14.1g(0.101mol)，滴毕保温反应4小时，用高效液色谱(HPLC)跟踪乙烯基甲膦酸乙酯消失，结束反应。冷却至常温，得2-氨基-4-(烷氧基甲膦酰基)丁腈溶液约50.3g。
在上一步所得的加成物溶液中，加入去离子水20ml和浓盐酸10ml，加热至沸腾，回流反应4h后，冷却至常温。将物料全部转移至250ml分液漏斗，静置分层。将下层水溶液分出，上层有机相加用去离子水5ml洗涤。洗涤后转移至蒸馏烧瓶。减压旋蒸至尽干，得白色结晶物15.5g。用无水乙醇重结晶，红外烘干过夜，得白色粉末2-氨基-4-(烷氧基甲膦酰基)丁腈15.1g，HLPC分析含量98.46％。以乙烯基甲膦酸乙酯计，收率77.43％。
实施例2
在500ml三口瓶中，加入二苯亚甲基氨基乙腈135g(0.55mol)、四氢呋喃100ml和乙烯基甲膦酸乙酯63g(0.45mol)；加少许乙醇钠，常温下搅拌反应6h，用薄层色谱(TLC)跟踪确定反应终点，得2-氨基-4-(烷氧基甲膦酰基)丁腈溶液231.1g。加去离子水50ml、浓盐酸10ml，加热至沸，回流反应6h。停止加热，冷却至常温，将物料全部转移至500ml分液漏斗，静置分层。小心分去下层水溶液，上层有机相用5ml去离子水洗涤。转移至蒸馏烧瓶，减压旋蒸至尽干，得白色结晶物70.2g。用无水乙醇重结晶，红外烘干12h，得白色粉末2-氨基-4-(烷氧基甲膦酰基)丁腈68.8g，HLPC分析含量98.39％。以乙烯基甲膦酸乙酯计，收率85.72％。
实施例3
在250ml反应瓶中，加入对硝基苯亚甲基氨基乙腈21.9g(0.104mol)、乙烯基甲膦酸甲酯12.4g(0.101mol)、二氯甲烷30ml和三乙胺10ml。搅拌升温至50℃，反应12h。用薄层色谱(TLC)跟踪确定反应终点，得2-氨基-4-(烷氧基甲膦酰基)丁腈溶液71.2g。加去离子水20ml、浓盐酸5ml，加热回流反应6h。冷却至常温，将物料全部转移至250ml分液漏斗，静置分层。小心分出下部油层，用5ml去离子水洗涤。转移至蒸馏烧瓶，减压旋蒸至尽干，得白色结晶14.2g。用无水乙醇重结晶，红外烘干过夜，得白色结晶粉末2-氨基-4-(烷氧基甲膦酰基)丁腈白色粉末13.6g，HLPC含量98.52％。以乙烯基甲膦酸甲酯计，收率81.79％。
Claims (6)
1.含膦酰基的α-氨基腈的制备方法，其特征是，包括如下步骤：
(1)将芳亚甲基氨基乙腈Ⅱ与乙烯基甲膦酸酯类化合物Ⅲ在有机溶剂中，碱性条件下进行反应，制备含膦酰基的α-氨基腈衍生物Ⅳ的步骤，反应温度为48～52℃，
其中，R为C1～C2的烷基，Ar为未取代的苯基或取代苯基；
(2)将含膦酰基的α-氨基腈衍生物Ⅳ与水反应，脱去芳亚甲基保护基，制备目标产物Ⅰ的步骤，
其中，所述的有机溶剂为甲醇、乙醇、异丙醇、乙醚、丁醚、四氢呋喃、二氧戊环、二氯甲烷、三氯甲烷、二氯乙烷、甲苯、二甲苯中任意一种；
碱性条件通过添加甲醇钠、乙醇钠或三乙胺实现。
2.根据权利要求1所述的制备方法，其特征是，步骤(1)中，芳亚甲基氨基乙腈、乙烯基甲膦酸烷基酯和有机溶剂的物质的量比是1:(0.8～1.0):(2～5)。
3.根据权利要求1所述的制备方法，其特征是，步骤(1)中，反应时间为4～24小时。
4.根据权利要求1所述的制备方法，其特征是，步骤(2)中，α-氨基腈衍生物与水的物质的量比是1:(2.0～20.0)。
5.根据权利要求1所述的制备方法，其特征是，步骤(2)中，反应温度为10～150℃。
6.根据权利要求1所述的制备方法，其特征是，步骤(2)中，反应时间为4～24小时。
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