CN1604896A - [1,4,5]-氧杂二氮杂䓬衍生物的制备方法 - Google Patents
[1,4,5]-氧杂二氮杂䓬衍生物的制备方法 Download PDFInfo
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- C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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Abstract
[1,4,5]-氧杂二氮杂䓬衍生物的制备方法,该方法使N,N’-二酰基肼与2,2’-二取代的二乙基醚反应,生成4,5-二酰基-[1,4,5]-氧杂二氮杂䓬,再使后者化合物与氢卤酸反应。
Description
本发明涉及[1,4,5]-氧杂二氮杂衍生物的新颖制备方法和它们在四氢吡唑烷二酮类除草剂的制备中作为中间体的用途。
按照PL 123646和SU 784 264,[1,4,5]-氧杂二氮杂衍生物是这样制备的,在溶剂DMFA中,使各种N,N’-二酰基化肼与2,2’-二氯二乙基醚反应。
现已惊人地发现,当在某些有机极性溶剂中进行N,N’-二酰基肼的反应生成对应的4,5-二酰基-[1,4,5]-氧杂二氮杂和其进一步的反应生成[1,4,5]-氧杂二氮杂时,[1,4,5]-氧杂二氮杂衍生物的制备在收率和纯度方面得以显著提高。
本发明因此涉及[1,4,5]-氧杂二氮杂衍生物的制备方法,该方法(1)在极性溶剂中,在碱的存在下,在升高的温度下,使N,N’-二酰基肼与2,2’-二取代的二乙基醚反应,生成对应的4,5-二酰基-[1,4,5]-氧杂二氮杂,和(2)可选地在极性溶剂中,在升高的温度下,使后者化合物与氢卤酸反应,生成对应的[1,4,5]-氧杂二氮杂,其中在反应步骤(1)中,使用选自DMSO、环丁砜、NMP和DMA的溶剂,在反应步骤(2)中,使用高沸点极性溶剂。
优选的N,N’-二酰基肼对应于式I R1-CO-NH-NH-CO-R2(I),其中R1和R2彼此独立地是氢、C1-C5烷基、C1-C5卤代烷基、C2-C5烯基、C2-C5炔基、苯基、烷基苯基、卤代苯基、烷氧基苯基、苄基、烷基苄基、卤代苄基或烷氧基苄基,或者R1和R2一起是C1-C4亚烷基、1,2-亚苯基或1,8-亚萘基。
优选的2,2’-二取代的二乙基醚对应于式IIR3-CH2CHR5-O-CHR6CH2-R4(II),其中R3和R4彼此独立地是卤素或式-OS(O)2R7基团,其中R7是C1-C5烷基、C1-C5卤代烷基、苯基、烷基苯基或卤代苯基,R5和R6彼此独立地是氢、C1-C5烷基、C2-C5烷氧基烷基、苯基、烷基苯基、烷氧基苯基或卤代苯基。
适合用在反应步骤(1)中的碱尤其是碱金属与碱土金属的氢氧化物、碳酸盐和醇化物,尤其是氢氧化钾和碳酸钾,和这类碱的混合物,尤其是氢氧化钾与碳酸钾的混合物。
氢卤酸优选地是氯化氢和溴化氢。
用在反应步骤(1)中的溶剂包括DMSO[(CH3)2SO]、环丁砜[(CH2)4SO2]、NMP[(CH2)3CONCH3]和DMA[CH3CON(CH3)2]及其混合物,优选为NMP,尤其是DMSO。在反应步骤(2)中,优选地使用沸点在100℃以上的醇,例如正丁醇、正戊醇、环己醇、苯酚、苯甲醇,尤其是乙二醇、二甘醇、甘油和C1-C4烷氧基-C1-C4醇,例如甲氧基异丙醇和乙氧基乙醇。
出现在式I和II化合物取代基定义中的烷基基团含有1至5个碳原子,例如是甲基、乙基、丙基、丁基或戊基及其支链异构体。烷氧基基团是从所述烷基基团衍生的。烯基和炔基基团各自具有2至5个碳原子,例如是乙烯基、丙烯基、乙炔基和丙炔基及其支链异构体,以及丁烯基、丁炔基、戊烯基、戊炔基及其支链与二不饱和的异构体。苯基基团可以进一步被烷基或烷氧基取代,例如各自具有1至4个碳原子,它们优选地占据邻位或间位或邻位和对位。卤素优选地是氟、氯或溴。
术语“升高的温度”尤其表示30至150℃的温度范围。尤其有利的是,反应步骤(1)的温度在60至100℃的范围内,反应步骤(2)的温度在30至60℃的范围内。
按照本发明用作原料的N,N’-二酰基肼是已知的,可以按照本身已知的方式得到,例如PL 123646 B1所述。
在反应步骤(1)中,优选的是使用1.5至4当量2,2’-二取代的二乙基醚,基于N,N’-二酰基肼而言。
在该反应步骤中所得到的4,5-二酰基-[1,4,5]-氧杂二氮杂尤其可以通过从醇中沉淀而得,例如甲醇、乙醇、丙醇、异丙醇、甲氧基异丙醇和乙氧基乙醇。一般而言,所得到的收率为40至76%,纯度超过95%。不过没有必要分离这些中间体;通过用反应步骤(2)的溶剂代替反应步骤(1)的溶剂,可以直接引入到下一步。
就有可能进一步提高反应步骤(1)的收率而言,可以加入碘化钾、冠(例如18-冠-6)和相转移催化剂(例如氯化苄基三乙铵、TBAB和Aliquat)。
通过使它们穿过反应混合物,可以直接加入在反应步骤(2)中除去酰基(保护基团)所需的氢卤酸。不过它们也可以是就地生成的,例如利用酰卤(例如乙酰氯)与作为溶剂存在的醇的反应。优选地,使用2至5当量氢卤酸,基于4,5-二酰基-[1,4,5]-氧杂二氮杂而言。
所分离的[1,4,5]-氧杂二氮杂盐的收率一般为80至95%,两个反应步骤共计60至70%。盐的纯度通常为约90%。
[1,4,5]-氧杂二氮杂衍生物的合成通常是这样进行的,向极性溶剂引入N,N’-二酰基肼,然后加入过量碱。然后在升高的温度下加入2,2’-二取代的二乙基醚,可选为过量,使反应混合物在该温度下维持约2至4小时。将混合物冷却至室温,过滤,借助蒸发浓缩从滤液中分离4,5-二酰基-[1,4,5]-氧杂二氮杂。然后将该化合物溶解或悬浮在高沸点醇中。然后在约50℃的温度下,使氢卤酸穿过该溶液或悬浮液,可选为过量。然后使反应混合物在该温度下维持另外12至14小时,脱气,冷却,过滤,将残余物洗涤,得到[1,4,5]-氧杂二氮杂的氢卤盐酸。
根据本发明的方法可以连续或分批(不连续)进行,分批操作是优选的。分批反应工艺和连续反应工艺都尤其是在搅拌着的容器或搅拌着的容器级联中进行的。
根据本发明的方法具有下列突出于现有技术方法的优点:
-它可以在工业规模上进行;
-它可以在多用途设备中进行;
-它以更高的纯度产出中间体和终产物;
-它以更高的收率产出中间体和终产物;
-它不必分离中间体;
-它允许相对低的反应温度,尤其在反应步骤(1)中。
按照本发明制备的[1,4,5]-氧杂二氮杂衍生物尤其在四氢吡唑烷二酮类除草剂的制备中用作中间体,该除草剂例如描述在WO99/47525中。
下列实施例进一步阐述本发明。
实施例1:4,5-二乙酰基-[1,4,5]-氧杂二氮杂的制备
以这样的方式将10.6g微细粉碎的85%氢氧化钾加入到9.3gN,N’-二乙酰肼与141g二甲基亚砜的溶液中,使温度不超过33℃。加热至80至85℃后,历经50分钟向反应混合物滴加23g 2,2’-二氯二乙基醚。使所得高流动性悬液在80至85℃下维持3小时,然后冷却至20至25℃,过滤,将过滤残余物用二甲基亚砜洗涤。借助蒸发浓缩从所合并的滤液中得到11.4g(76.0%)4,5-二乙酰基-[1,4,5]-氧杂二氮杂。
实施例2:4,5-二乙酰基-[1,4,5]-氧杂二氮杂的制备
将105.6g微细粉碎的85%氢氧化钾加入到92.9g N,N’-二乙酰肼与1410g二甲基亚砜的溶液中。当反应热已经消散时,加入229.9g 2,2’-二氯二乙基醚,然后加入221.1g微细研磨的碳酸钾。将反应混合物加热至70℃,在70至75℃下维持2小时,然后冷却至20至25℃,过滤,将过滤残余物用二甲基亚砜洗涤。蒸发浓缩所合并的滤液,得到油状物,向其中加入157g异丙醇。冷却至-10℃后,进行过滤,将结晶残余物用异丙醇洗涤。将残余物干燥后,得到99.4g(65.1%)4,5-二乙酰基-[1,4,5]-氧杂二氮杂,纯度为97.6%。
实施例3:盐酸[1,4,5]-氧杂二氮杂的制备
历经8至10小时,使19.7g氯化氢(无水)穿过19.1g 4,5-二乙酰基-[1,4,5]-氧杂二氮杂与70g二甘醇的溶液,然后使反应混合物在43至45℃下维持10至12小时。反应悬浮液在40至45℃下脱气后,在10℃的温度下进行过滤,将残余物用冷的乙酸甲酯洗涤。将残余物干燥后,得到13.2g(85.0%)盐酸[1,4,5]-氧杂二氮杂,纯度为90.0%,在晶体中结合有大约8.5%二甘醇。
实施例4-8:4,5-二乙酰基-[1,4,5]-氧杂二氮杂的制备
将39.6g氢氧化钾粉末85%(0.6mol)加入到35g二乙酰基肼(0.3mol)与560ml溶剂(见表1)的混合物中。当反应热已经消散时,加入85.8g 2,2-二氯二乙基醚(0.6mol);将反应混合物加热至80℃,在80-90℃下维持5小时。然后将混合物冷却至20℃,过滤,将过滤残余物用溶剂洗涤。收率以标题化合物在所合并的滤液中的含量表示。可以见到,按照本发明所使用的溶剂(试验4-7)得到4,5-二乙酰基-[1,4,5]-氧杂二氮杂的收率大大好于N,N-二甲基甲酰胺,该溶剂是上述现有技术已知的(DMFA,对比试验8)。
表1:
试验No. | 溶剂 | [g] | [ml] | 收率[%] | 加入 |
4 | 2-甲基吡咯烷酮 | 578 | 560 | 39.1 | |
5 | 二甲基亚砜 | 616 | 560 | 73.2 | |
6 | N,N-二甲基乙酰胺 | 527.5 | 560 | 41.2 | |
7 | N,N-二甲基乙酰胺 | 530 | 562.5 | 46.5 | 加入5mol%氯化苄基三乙铵作为相转移催化剂 |
8 | N,N-二甲基甲酰胺 | 531 | 560 | 15.2 |
实施例9-13:4,5-二乙酰基-[1,4,5]-氧杂二氮杂的制备
将35g二乙酰基肼(0.3mol)、124.4g或165.8g研磨的碳酸钾(分别为0.9或1.2mol)、85.8g 2,2-二氯二乙基醚(0.6mol)与560ml溶剂(见表2)的混合物加热至125℃,在125-130℃或80-90℃(在DMSO的情况下)下维持5小时。然后将混合物冷却至20℃,过滤,将过滤残余物用溶剂洗涤。收率以标题化合物在所合并的滤液中的含量表示。
表2:
试验No. | 溶剂 | [g] | [ml] | 收率[%] | 碱的量[eq.] | 温度[℃] |
9 | N,N-二甲基乙酰胺 | 527.5 | 560 | 63.0 | 3 | 125-130 |
10 | 2-甲基吡咯烷酮 | 578 | 560 | 61.4 | 3 | 125-130 |
11 | 环丁砜 | 711 | 560 | 60.3 | 3 | 125-130 |
12 | 二甲基亚砜 | 616 | 560 | 64.5 | 3 | 80-90 |
13 | 二甲基亚砜 | 616 | 560 | 72.8 | 4 | 80-90 |
实施例14:1,2-(邻苯二甲酰)二氮杂-5-氧杂环庚烷的制备
将39.6g氢氧化钾粉末85%(0.6mol)加入到49.1g 2,3-二氢-1,4-酞嗪二酮(0.3mol)与616g二甲基亚砜的混合物中。当反应热已经消散时,加入85.8g 2,2-二氯二乙基醚(0.6mol),将反应混合物加热至80℃,在80-90℃下维持5小时。然后将混合物冷却至20℃,过滤,将过滤残余物用二甲基亚砜洗涤。借助蒸馏从所合并的滤液中除去溶剂,向残留的油状物中加入100g正戊醇,产物结晶出来。过滤,洗涤过滤残余物,得到22.5g或25%标题化合物。
实施例15:4,5-二乙酰基-[1,4,5]-氧杂二氮杂的制备
将11.6g二乙酰基肼(0.1mol)、29.0g研磨的碳酸钾(0.21mol)、31.5g2,2-二甲磺酰基二乙基醚(0.12mol)与177g二甲基亚砜的混合物加热至80℃,在80-85℃下维持6小时。然后将混合物冷却至20℃,过滤,将过滤残余物用50g二甲基亚砜洗涤。借助蒸发完全浓缩滤液,向油性残余物加入20ml水。用乙酸乙酯萃取三次,所合并的萃取液经硫酸钠干燥,蒸发浓缩,残余物从正戊醇中结晶,得到10.8g或58.4%标题化合物。
Claims (2)
1、[1,4,5]-氧杂二氮杂衍生物的制备方法,该方法(1)在极性溶剂中,在碱的存在下,在升高的温度下,使N,N’-二酰基肼与2,2’-二取代的二乙基醚反应,生成对应的4,5-二酰基-[1,4,5]-氧杂二氮杂,和(2)可选地在极性溶剂中,在升高的温度下,使后者化合物与氢卤酸反应,生成对应的[1,4,5]-氧杂二氮杂,其中在反应步骤(1)中,使用选自DMSO、环丁砜、NMP和DMA的溶剂,在反应步骤(2)中,使用高沸点极性溶剂。
2、根据权利要求1所制备的[1,4,5]-氧杂二氮杂在四氢吡唑烷二酮类除草剂制备中的用途。
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CN107445915A (zh) * | 2017-09-18 | 2017-12-08 | 张家港九力新材料科技有限公司 | 一种4,5‑二叔丁氧羰基‑[1,4,5]氧二氮杂庚烷制备方法 |
CN108017593A (zh) * | 2017-12-06 | 2018-05-11 | 东南大学 | 一种简便高效的1-氧-4,5-二氮杂环庚烷合成方法 |
WO2018120093A1 (zh) * | 2016-12-30 | 2018-07-05 | 泸州东方农化有限公司 | 一种制备氧二氮杂环化合物的工艺及其应用 |
CN108264493A (zh) * | 2016-12-30 | 2018-07-10 | 泸州东方农化有限公司 | 一种制备氧二氮杂环化合物的工艺及其应用 |
CN112522340A (zh) * | 2019-09-19 | 2021-03-19 | 四川利尔生物科技有限公司 | 酶催化水解制备1-氧-4,5-二氮杂环庚烷的方法 |
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PT1838683E (pt) * | 2004-10-27 | 2009-07-22 | Syngeta Participations Ag | Um processo para a preparação de derivados de [1,4,5]-oxadiazepina |
AR087008A1 (es) | 2011-06-22 | 2014-02-05 | Syngenta Participations Ag | Derivados de n-oxi-pirazolo-triazepina-diona |
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AU7514600A (en) * | 1999-09-07 | 2001-04-10 | Syngenta Participations Ag | Novel herbicides |
PT1838683E (pt) * | 2004-10-27 | 2009-07-22 | Syngeta Participations Ag | Um processo para a preparação de derivados de [1,4,5]-oxadiazepina |
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