CN116262675A - 一种制备丙二腈肟醚类化合物的方法 - Google Patents
一种制备丙二腈肟醚类化合物的方法 Download PDFInfo
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- -1 malononitrile oxime ether compound Chemical class 0.000 title claims abstract description 63
- 238000000034 method Methods 0.000 title claims abstract description 23
- 239000012024 dehydrating agents Substances 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 230000008569 process Effects 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 238000006297 dehydration reaction Methods 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 10
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 150000002825 nitriles Chemical class 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- XEKIGMYTIIXBAM-UHFFFAOYSA-N 3,3,3-trichloropropanoyl 3,3,3-trichloropropanoate Chemical compound ClC(Cl)(Cl)CC(=O)OC(=O)CC(Cl)(Cl)Cl XEKIGMYTIIXBAM-UHFFFAOYSA-N 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 claims description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
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- LAYPMCGIWDGYKX-UHFFFAOYSA-N trichloromethyl hydrogen carbonate Chemical compound OC(=O)OC(Cl)(Cl)Cl LAYPMCGIWDGYKX-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 7
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 abstract description 5
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 abstract description 3
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- HMDMEJOMSHIJKM-UHFFFAOYSA-N ClC1=C(Cl)C=CC(CON=C(C#N)C#N)=C1 Chemical compound ClC1=C(Cl)C=CC(CON=C(C#N)C#N)=C1 HMDMEJOMSHIJKM-UHFFFAOYSA-N 0.000 description 3
- GKJUNJFFYOUUPI-UHFFFAOYSA-N N=1C(CON=C(C#N)C#N)=CSC=1C1=CC=CC=C1 Chemical compound N=1C(CON=C(C#N)C#N)=CSC=1C1=CC=CC=C1 GKJUNJFFYOUUPI-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- RSBZTZSIXYFCDN-UHFFFAOYSA-N 2-[(2-chloro-1,3-thiazol-5-yl)methoxyimino]propanedinitrile Chemical compound ClC=1SC(=CN=1)CON=C(C#N)C#N RSBZTZSIXYFCDN-UHFFFAOYSA-N 0.000 description 2
- HIJBVMHFMLHOTA-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methoxyimino]propanedinitrile Chemical compound COC1=CC=C(C=C1)CON=C(C#N)C#N HIJBVMHFMLHOTA-UHFFFAOYSA-N 0.000 description 2
- IZQBHEAQKKOCOH-UHFFFAOYSA-N 2-[[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methoxyimino]propanedinitrile Chemical compound ClC1=CC=C(C=C1)C=1SC=C(N=1)CON=C(C#N)C#N IZQBHEAQKKOCOH-UHFFFAOYSA-N 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
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- 208000031888 Mycoses Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- 235000011121 sodium hydroxide Nutrition 0.000 description 2
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- YKECSFNZQGAHFU-UHFFFAOYSA-N 2-iminoacetamide Chemical compound NC(=O)C=N YKECSFNZQGAHFU-UHFFFAOYSA-N 0.000 description 1
- WYKHSBAVLOPISI-UHFFFAOYSA-N 2-phenyl-1,3-thiazole Chemical compound C1=CSC(C=2C=CC=CC=2)=N1 WYKHSBAVLOPISI-UHFFFAOYSA-N 0.000 description 1
- KCZHDRHOSNPTJZ-UHFFFAOYSA-N 3,3,3-trifluoropropanoyl 3,3,3-trifluoropropanoate Chemical compound FC(F)(F)CC(=O)OC(=O)CC(F)(F)F KCZHDRHOSNPTJZ-UHFFFAOYSA-N 0.000 description 1
- GHHWFZKXGGDHJI-UHFFFAOYSA-N 3-(3,4-dichlorophenoxy)propanenitrile Chemical compound ClC1=CC=C(OCCC#N)C=C1Cl GHHWFZKXGGDHJI-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical group CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
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- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- YKUHPXMDZYYZBQ-UHFFFAOYSA-N iminomalononitrile Chemical compound N#CC(=N)C#N YKUHPXMDZYYZBQ-UHFFFAOYSA-N 0.000 description 1
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
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- C07—ORGANIC CHEMISTRY
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/20—Preparation of carboxylic acid nitriles by dehydration of carboxylic acid amides
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- 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
- C07D213/60—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 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
- C07D213/61—Halogen atoms or nitro radicals
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- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
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- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
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Abstract
本发明涉及有机合成领域，具体而言，涉及一种制备丙二腈肟醚类化合物的方法。所述丙二腈肟醚类化合物具有式(Ⅶ)所示结构，
Description
技术领域
本发明涉及有机合成领域，具体而言，涉及一种制备丙二腈肟醚类化合物的方法。
背景技术
现有文献提供了一种对植物细菌病害和真菌病害具有良好防治效果的丙二腈肟醚类化合物的合成方法，如下式：
其中：LG表示离去基团，选自卤素或其它常规的离核基团，例如三氟甲基、甲磺酸基或甲苯磺酸基等；M表示阳离子，例如Na+、K+、CS +、Ag+或NH4 +等；W表示各种芳基或杂芳基；L表示各种链桥；W选自芳基或杂芳基。
但是，采用现有方法制备通式I所示的丙二腈肟醚类化合物时，收率普遍低于60％，且制备通式III所示化合物的原料丙二腈的价格较高，进而导致通式III所示化合物的成本也较高。
专利201810771581.7中记载丙二腈肟醚类化合物时以式(Ⅵ)做原料，使用三氯氧磷等做脱水剂、甲苯做溶剂一步法制备式(Ⅶ)收率提高至80％。但该方法三氯氧磷需要量过大，产生大量含磷酸和氯化氢废水，工业化制备过程中有一定困难。
因此，如何开发出一种更适合工业化生产的合成方法是本领域技术人员亟需解决的难题。
发明内容
本发明的主要目以解决采用现有方法制备丙二腈肟醚类化合物时存在产物收率低和三废量大、制备成本高的问题，提供一种制备丙二腈肟醚类化合物的方法。
为了实现上述目的，本发明采用技术方案为：
一种制备丙二腈肟醚类化合物的方法，所述丙二腈肟醚类化合物具有式(Ⅶ)所示结构，
所述制备方法为：原料(Ⅵ)在溶剂存在下与脱水剂在0～40℃下反应，得到式(Ⅶ)所示丙二腈肟醚类化合物；
所述脱水反应在脱水剂和碱的作用下进行反应，得到式(Ⅶ)所示丙二腈肟醚类化合物。
所述原料(Ⅳ)然后在溶剂和脱水剂的作用下，在碱的存在下，于0～40℃，反应0.5～24h。
所述脱水剂选自乙酸酐、三氟甲基乙酸酐、三氯甲基乙酸酐、三氯乙酰氯、甲基磺酰氯、碳酸三氯甲基酯、氯化亚砜、三氯氧磷和五氧化二磷中的一种或多种。优选为三氯氧磷、三氟乙酸酐、三氯乙酰氯中的一种或多种。
所述脱水反应过程中，所述原料(Ⅵ)与所述脱水剂的摩尔数比为1:1～5，优选为1:1～2。
所述溶剂选自卤代烷烃类有机物、芳烃有机物、腈类有机物和DMF中的一种或多种，优选为二氯甲烷、二氯乙烷、三氯甲烷、乙腈、甲苯或DMF；所述溶剂的使用量为所述原料(Ⅵ)重量的1-10倍，优选的使用量为2～5倍。
所述碱为氢氧化钾、碳酸钾、碳酸钠、三乙胺、吡啶、哌啶、苯胺的一种或多种，优选为三乙胺或/和吡啶；所述碱的用量为所述原料(Ⅵ)摩尔的2～10倍，优选为2-3倍。
所述反应后的后处理过程为加水淬灭反应，回收碱及溶剂可回收套用。
所述反应后可进一步通过结晶纯化。
结晶使用溶剂为甲醇、乙醇、异丙醇等或它们的水溶液，优选的溶剂为甲醇或乙醇。
所述重结晶溶剂的使用量为所述中间体化合物的重量比为0.5～10倍，优选的使用量为1～2倍。
所述脱水反应采用的脱水体系可在酰胺制备腈或氰的反应中应用。
与现有技术相比本发明的有点在于：
本发明制备丙二腈肟醚类化合物以及由酰胺类化合物制备酰腈类化合物时，脱水过程中采用特定脱水剂，或将特定脱水剂与碱配合，并于温和条件下脱水制备丙二腈肟醚类、腈类或氰类化合物，脱水过程简单、无需特别处理，且仅通过一步反应即可获得所需的丙二腈肟醚类、腈类或氰类化合物；进一步的说：
1.本发明使用的脱水剂为常规化工原料，价格大致在6000元/吨以内，进而价格适中；本发明通过特定的脱水剂，以及在碱的存在下进行脱水制备丙二腈肟醚类化合物，碱在反应中起缚酸剂作用。
2.本发明在反应条件温和，无高温、高压反应、反应完全，使反应副产物少、设备简单，进而使得本发明制备产品收率及含量高，生产成本降低。
3.本发明三废量相对较少，溶剂及碱可回收套用；
4.本发明适用范围较宽，不仅适用于丙二腈类化合物的制备也适用于其它烷基或芳香烃类酰胺脱水制备腈类或氰类化合物的反应。
具体实施方式
需要说明的是，在不冲突的情况下，本申请中的实施例及实施例中的特征可以相互组合。下面将结合实施例来详细说明本发明。
本发明制备丙二腈肟醚类化合物化合物的方法，合成路线如下：
上述制备方法中，以化合物(Ⅵ)所示的中间体化合物。然后在溶剂和脱水剂的作用下，使式(Ⅵ)所示的中间体化合物发生脱水，得到所需的丙二腈肟醚类化合物。且仅通过一步反应即可获得所需的产品。因而采用上述制备方法有利于提高制备丙二腈肟醚类化合物的产品质量和收率，并降低工艺成本。
上述丙二腈肟醚类化合物是一种对植物细菌病害和真菌病害具有良好防治效果化合物，因而上述制备方法为其进行产业化开发提供了一种新的和有效途径。
以下结合具体实施例对本申请作进一步详细描述，这些实施例不能理解为限制本申请所要求保护的范围。
实施例1
2-[((2-苯基噻唑-4-基)甲氧基)亚胺基]丙二腈的制备：
向反应瓶中加入2-氰基-2-[((2-苯基噻唑-4-基)甲氧基)亚胺基]乙酰胺(11.57g，40.0mmol)、三氯乙酰氯(10.92g，60.0mmol)、三乙胺(8.08g，80.0mmol)和三氯甲烷(80mL)，升温至40℃保温反应8h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出三氯甲烷，残余物经乙醇重结晶得2-[((2-苯基噻唑-4-基)甲氧基)亚胺基]丙二腈，浅黄色固体10.4g，含量为98.2％收率95％(以2-氰基-2-[((2-苯基噻唑-4-基)甲氧基)亚胺基]乙酰胺计)。
2-[((2-苯基噻唑-4-基)甲氧基)亚胺基]丙二腈的1HNMR(600MHz,CDCl3)δ7.95-7.94(m,2H),7.46-7.45(m,3H),7.40(s,1H),5.67(s,2H)。
实施例2
2-[((3，4-二氯苯基)甲氧基)亚胺基]丙二腈的制备：
向反应瓶中加入2-氰基-2-[((3，4-二氯苯基)甲氧基)亚胺基]乙酰胺(11.00g，40.0mmol)、三氯乙酰氯(10.92g，60.0mmol)和二氯甲烷(80mL)、三乙胺(8.16g，80.0mmol)，8～10℃保温反应4h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，常压蒸出二氯甲烷，残余物经甲醇重结晶得2-[((3，4-二氯苯基)甲氧基)亚胺基]丙二腈，白色固体10.05g，含量98.5％，收率96.5％(以2-氰基-2-[((3，4-二氯苯基)甲氧基)亚胺基]乙酰胺计)。
2-[((3，4-二氯苯基)甲氧基)亚胺基]丙二腈的1HNMR(600MHz,CDCl3)δ7.50(d,1H),7.48(d,1H),7.23(dd,1H),5.46(s,2H)。
实施例3
2-[((2-(4-氯苯基)噻唑-4-基)甲氧基)亚胺基]丙二腈的制备：
向反应瓶中加入2-氰基-2-[((2-(4-氯苯基)噻唑-4-基)甲氧基)亚胺基]乙酰胺(12.96g，40.0mmol)、吡啶(6.95g,88.0mmol)三氯乙酰氯(10.92g，60.0mmol)和三氯甲烷(80mL)，室温下反应5h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出三氯甲烷，残余物经异丙醇重结晶得2-[((2-(4-氯苯基)噻唑-4-基)甲氧基)亚胺基]丙二腈，浅黄色固体11.62g，收率95％(以2-氰基-2-[((2-(4-氯苯基)噻唑-4-基)甲氧基)亚胺基]乙酰胺计)。
2-[((2-(4-氯苯基)噻唑-4-基)甲氧基)亚胺基]丙二腈的1HNMR(300MHz,CDCl3)δ7.89(d,2H),7.44(d,2H),7.42(s,1H),5.67(s,2H)。
实施例4
2-[((4-甲氧基苯基)甲氧基)亚胺基]丙二腈的制备：
向反应瓶中加入2-氰基-2-[((4-甲氧基苯基)甲氧基)亚胺基]乙酰胺(9.43g，40.0mmol)、三氯乙酸酐(24.68g，80.0mmol)、吡啶(7.98g，100.0mmol)和甲苯(80mL)，10℃保温反应6h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出甲苯，残余物经乙醇重结晶得浅黄色固体8.40g，收率96.5％(以2-氰基-2-[((4-甲氧基苯基)甲氧基)亚胺基]乙酰胺计)。
2-[((4-甲氧基苯基)甲氧基)亚胺基]丙二腈的1HNMR(300MHz,CDCl3)δ7.33(dd,2H),6.93(dd,2H),5.46(s,2H),3.83(s,3H)。
实施例5
2-[((6-氯吡啶-3-基)甲氧基)亚胺基]丙二腈的制备：
向反应瓶中加入2-氰基-2-[((6-氯吡啶-3-基)甲氧基)亚胺基]乙酰胺(9.64g，40.0mmol)、三氯乙酰氯(14.56g，80.0mmol)、三乙胺(8.16g,80.0mmol)和二氯甲烷(80mL)，室温下反应6h，TLC监测至反应完全。搅拌下加入水，充分溶解，静置分层。水相加入液碱中和、静置分层，上层水液加入固碱干燥回收三乙胺回收套用。有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，常用蒸出二氯甲烷，残余物经甲醇重结晶得2-[((6-氯吡啶-3-基)甲氧基)亚胺基]丙二腈，淡黄色固体8.52g，收率95.5％(以2-氰基-2-[((6-氯吡啶-3-基)甲氧基)亚胺基]乙酰胺计)。
2-[((6-氯吡啶-3-基)甲氧基)亚胺基]丙二腈的1HNMR(600MHz,CDCl3)δ8.45(s,1H),7.71(d,1H),7.43(d,1H),5.52(s,2H)。
实施例6
2-[((6-氯吡啶-3-基)甲氧基)亚胺基]丙二腈的制备：
向反应瓶中加入2-氰基-2-[((2-氯噻唑-5-基)甲氧基)亚胺基]乙酰胺(9.89g，40.0mmol)、三氯乙酰氯(27.3g，60.0mmol)、三乙胺(10.20g,100.0mmol)和三氯甲烷(80mL)，升温至40℃保温反应6h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出三氯甲烷，残余物经柱色谱分离纯化得2-[((2-氯噻唑-5-基)甲氧基)亚胺基]丙二腈，黄色油8.61g，收率94.0％(以2-氰基-2-[((2-氯噻唑-5-基)甲氧基)亚胺基]乙酰胺计)。
2-[((2-氯噻唑-5-基)甲氧基)亚胺基]丙二腈的1HNMR(600MHz,CDCl3)δ7.65(s,1H),5.62(s,2H)。
实施例7
向反应釜中加入中间体1(38.1Kg，0.10Kmol)、三氯乙酰氯(27.6Kg，0.15Kmol)、三乙胺(25.5Kg,0.25Kmol)和二氯乙烷(80L)，0～10℃保温反应6h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水100L，充分溶解，静置分层.有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出二氯乙烷，残余物经乙醇重结晶得浅黄色固体35.6Kg,含量98.2％，收率95.2％
实施例8
向反应瓶中加入2-(2-苯基噻唑)-4-基)乙酰胺(8.81g，40.0mmol)、三氯乙酸酐(24.68g，80.0mmol)、吡啶(7.98g，100.0mmol)和甲苯(80mL)，10℃保温反应6h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出甲苯，残余物经乙醇重结晶得2-(2-苯基噻唑)-4-基)乙腈，浅黄色固体7.72g，收率96.5％。
实施例9
向反应瓶中加入3-(3、4-二氯苯氧基)丙酰胺(9.41g，40.0mmol)、三氯乙酸酐(24.68g，80.0mmol)、吡啶(7.98g，100.0mmol)和甲苯(80mL)，10℃保温反应6h，TLC监测至反应完全。反应液降温至室温，搅拌下加入水，充分溶解，静置分层，有机相用饱和食盐水洗涤，无水硫酸镁干燥，过滤，减压蒸出甲苯，残余物经乙醇重结晶得3-(3、4-二氯苯氧基)丙腈，浅黄色固体8.30g，收率96.5％。
从以上的描述中，可以看出，本发明上述的实施例实现了如下技术效果：
而由于背景技术可知，通式I所示丙二腈肟醚类化合物的收率普遍低于80％。比较实施例1至7可知，式(Ⅶ)所示的丙二腈肟醚类化合物的收率均大于90％。由此可知采用本申请提供的制备方法能够大大提升丙二腈肟醚类化合物的收率。
以上所述仅为本发明的优选实施例而已，并不用于限制本发明，对于本领域的技术人员来说，本发明可以有各种更改和变化。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (10)
1.一种制备丙二腈肟醚类化合物的方法，其特征在于，所述丙二腈肟醚类化合物具有式(Ⅶ)所示结构，
所述制备方法为：原料(Ⅵ)在溶剂存在下与脱水剂在0～40℃下反应，得到式(Ⅶ)所示丙二腈肟醚类化合物；
2.按权利要求1所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述脱水反应在脱水剂和碱的作用下进行反应，得到式(Ⅶ)所示丙二腈肟醚类化合物。
3.按权利要去1或2所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述原料(Ⅳ)然后在溶剂和脱水剂的作用下，在碱的存在下，于0～40℃，反应0.5～24h。
4.按权利要去3所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述脱水剂选自乙酸酐、三氟甲基乙酸酐、三氯甲基乙酸酐、三氯乙酰氯、甲基磺酰氯、碳酸三氯甲基酯、氯化亚砜、三氯氧磷和五氧化二磷中的一种或多种。
5.按权利要去3所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述脱水反应过程中，所述原料(Ⅵ)与所述脱水剂的摩尔数比为1:1～5。
6.按权利要去3所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述溶剂选自卤代烷烃类有机物、芳烃有机物、腈类有机物和DMF中的一种或多种；所述溶剂的使用量为所述原料(Ⅵ)重量的1-10倍。
7.按权利要去3所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述碱为氢氧化钾、碳酸钾、碳酸钠、三乙胺、吡啶、哌啶、苯胺的一种或多种；所述碱的用量为所述原料(Ⅵ)摩尔比的2～10倍。
8.按权利要去3所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述反应后的后处理过程为加水淬灭反应，回收碱及溶剂可回收套用。
9.按权利要去1所述的制备丙二腈肟醚类化合物的方法，其特征在于，所述反应后可进一步通过结晶纯化。
10.按权利要求1所述的制备方法，其特征在于：所述脱水反应采用的脱水体系可在酰胺制备腈或氰的反应中应用。
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