CN1055609C - 农用杀菌剂腈菌唑的制备方法 - Google Patents
农用杀菌剂腈菌唑的制备方法 Download PDFInfo
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- HZJKXKUJVSEEFU-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)hexanenitrile Chemical compound C=1C=C(Cl)C=CC=1C(CCCC)(C#N)CN1C=NC=N1 HZJKXKUJVSEEFU-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 239000005811 Myclobutanil Substances 0.000 title claims abstract description 10
- 230000000855 fungicidal effect Effects 0.000 title claims abstract description 9
- 239000000417 fungicide Substances 0.000 title claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 title abstract description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- IVYMIRMKXZAHRV-UHFFFAOYSA-N 4-chlorophenylacetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1 IVYMIRMKXZAHRV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000000605 extraction Methods 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 4
- IJDNQMDRQITEOD-UHFFFAOYSA-N sec-butylidene Natural products CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 150000002825 nitriles Chemical class 0.000 claims description 24
- 241000894006 Bacteria Species 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 150000003851 azoles Chemical class 0.000 claims description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000004821 distillation Methods 0.000 claims description 5
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 5
- KSWSBTWLMBWIAN-UHFFFAOYSA-O ClC[N+]=1NN=CC1 Chemical class ClC[N+]=1NN=CC1 KSWSBTWLMBWIAN-UHFFFAOYSA-O 0.000 claims description 4
- 239000003444 phase transfer catalyst Substances 0.000 claims description 4
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 230000008034 disappearance Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 3
- 239000011230 binding agent Substances 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- KENWYAZHACTWDC-UHFFFAOYSA-N 2-(4-chlorophenyl)hexanenitrile Chemical compound CCCCC(C#N)C1=CC=C(Cl)C=C1 KENWYAZHACTWDC-UHFFFAOYSA-N 0.000 abstract 1
- MKCKJMICTQSOKQ-UHFFFAOYSA-N Cl.ClCc1cn[nH]n1 Chemical compound Cl.ClCc1cn[nH]n1 MKCKJMICTQSOKQ-UHFFFAOYSA-N 0.000 abstract 1
- 230000002140 halogenating effect Effects 0.000 abstract 1
- 230000009897 systematic effect Effects 0.000 abstract 1
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 6
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- PXNMFQMREJNQQT-UHFFFAOYSA-N 1-(chloromethyl)-1,2,4-triazole Chemical class ClCN1C=NC=N1 PXNMFQMREJNQQT-UHFFFAOYSA-N 0.000 description 3
- 206010039509 Scab Diseases 0.000 description 3
- 241000209140 Triticum Species 0.000 description 3
- 235000021307 Triticum Nutrition 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 2
- 241000207199 Citrus Species 0.000 description 2
- 241000221785 Erysiphales Species 0.000 description 2
- 241000228150 Penicillium chrysogenum Species 0.000 description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 description 2
- 240000006365 Vitis vinifera Species 0.000 description 2
- 235000014787 Vitis vinifera Nutrition 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 235000020971 citrus fruits Nutrition 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- WCRAKJMHCWUABB-UHFFFAOYSA-N 1,2,4-triazol-1-ylmethanol Chemical compound OCN1C=NC=N1 WCRAKJMHCWUABB-UHFFFAOYSA-N 0.000 description 1
- -1 4-triazolyl methyl Chemical group 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
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- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
本发明涉及农用杀菌剂腈菌唑的制备方法。腈菌唑的化学名称为2-(4-氯苯基)-2-(1H-1，2，4-三唑基甲基)己腈，是一种高效低毒内吸性农用杀菌剂。本发明以对氯苯乙腈为原料，与卤代正丁烷反应得2-(4-氯苯基)己腈，然后加入1～5倍溶剂二甲基亚砜及缚酸剂氢氧化钠，搅拌加入氯甲基三唑盐酸盐，反应物加水搅拌，用氯仿萃取，脱溶得腈菌唑。本方法避免采用二溴甲烷，使生产成本降低，以利于腈菌唑作为农用杀菌剂广泛应用。
Description
本发明涉及农用杀菌剂腈菌唑的一种制备方法，该杀菌剂主要用于防治苹果黑星病、白粉病、葡萄黑腐病等果树病害及麦类黑穗病、黑粉病、小麦颖枯病菌、镰刀菌和麦类核腔菌引起的种传病害，也可防治收获后柑桔的青霉菌。
腈菌唑的化学名称为2-(4-氯苯基)-2-(1H-1，2，4-三唑基甲基)己腈，化学结构式为
是-种高效低毒内吸性农用杀菌剂，用于防治苹果黑星病、白粉病、葡萄黑星病、麦类黑穗病、黑粉病及小麦颖枯病菌、镰刀菌、核腔菌引起的种传病害，也可防治收获后柑桔的青霉菌。欧州专利EP145,294提出了腈菌唑的制备方法：用对氯苯乙腈与卤代正丁烷在氢氧化钠及相转移催化剂(PTC)存在下进行烷基化反应，制得2-(4-氯苯基)己腈(下称化合物1)，将其与二溴甲烷反应制得1-溴-2-氰基-2-(4-氯苯基)己烷(化合物2)，最后与1，2，4-三唑钾盐缩合得腈菌唑(化合物3)。
反应式如下：
由于我国二溴甲烷来源少，需要进口，价格昂贵，因而用上述方法制备腈菌唑杀菌剂生产成本过高，难以推广应用。
本发明的目的是提供一种制备腈菌唑杀菌剂的方法，它避免使用二溴甲烷，以降低腈菌唑的生产成本，利于大规模生产和广泛应用。
本发明腈菌唑的制备方法以对氯苯乙腈为原料，在相转移催化剂四乙基溴化铵存在下加入氯代正丁烷，并滴加氢氧化钠反应得2-(4-氯苯基)己腈(化合物1)，在化合物1中加入1～5倍(重量)溶剂二甲基亚砜及过量的缚酸剂氢氧化钠，搅拌下缓缓加入与化合物1等摩尔量的氯甲基三唑盐酸盐，反应至化合物1消失，加适量水搅拌用氯仿萃取，蒸馏脱溶得腈菌唑。
化学反应如下：
本发明中，化合物1与氯甲基三唑盐酸盐的反应温度以10～30℃为佳，温度太低，反应速度太慢，温度过高，会引起氯甲基三唑盐酸盐的分解。上述反应中的缚酸剂也可采用氢氧化钾。氯甲基三唑盐酸盐可根据欧州专利EP60,223和EP63,099中公开的方法制备，即先由1H-1，2，4-三唑与多聚甲醛在三乙胺存在下反应，待反应液澄清后加入丙酮重结晶得1-羟甲基-1H-1，2，4-三唑，然后与氯化亚砜反应，用氯仿洗涤除去残留的过量氯化亚砜，即得1-氯甲基-1H-1，2，4-三唑盐酸盐。
采用本发明制腈菌唑的方法，使腈菌唑的制备过程避免使用昂贵的二溴甲烷，因而生产成本降低，有利于这种杀菌剂的大规模生产和更广泛的应用。
下面通过实施例进一步说明本发明的制备工艺。
实施例：腈菌唑的制备步骤
1. 1-氯甲基-1H-1，2，4-三唑盐酸盐的制备
a.100毫升三口瓶加装搅拌器、温度计和回流冷凝管瓶内加入28克1H-1，2，4-三唑和12克多聚甲醛，数滴三乙胺，于70℃下搅拌反应，直至反应液澄清，加入丙酮重结晶，得1-羟甲基-1H-1，2，4-三唑，熔点65～67℃。
b.250毫升的四口瓶加装搅拌器、温度计、回流冷凝管、滴液漏斗，瓶内加入100克氯化亚砜，升温至55℃，搅拌下缓缓加入33克1-羟甲基-1H-1，2，4-三唑，加完后升温至回流，直至尾气中无酸性气体放出，即为反应终点，过量的氯化亚砜蒸馏除去，再用氯仿洗去残留的氯化亚砜，即得1-氯甲基-1H-1，2，4-三唑盐酸盐，熔点120～125℃，分子式为
2. 2-(4-氯苯基)己腈(即上述化合物1)的制备
1000毫升三口瓶加装搅拌器、温度计、滴液漏斗，瓶内加入152克对氯苯乙腈、18C克氯代正丁烷、4.2克四乙基溴化铵，保持反应温度20～25℃，搅拌下滴入320克50％的氢氧化钠，气谱跟踪至原料对氯苯乙腈消失，加适量水搅拌静置分层，水层用氯仿萃取三次，有机层用水洗二次，合并有机层，蒸馏收集146～150℃/7～8mmHg馏份，即得无色粘稠液2-(4-氯苯基)己腈。
3. 2-(4-氯苯基)-2-(1H-1，2，4-三唑基甲基)己腈(即腈菌唑)的制备
250毫升三口瓶加装搅拌机、温度计，先加17.5克2-(4-氯苯基)己腈(含量99％)，26.5克50％浓度的氢氧化钠水溶液，60毫升二甲基亚砜，搅拌下缓缓加入15克1-氯甲基-1H-1，2，4-三唑盐酸盐，保持反应温度在25℃左右，气谱跟踪至2-(4-氯苯基)己腈消失，即到达反应终点，加水搅拌，用氯仿萃取三次，每次60克氯仿，合并有机层，蒸馏除去氯仿得产品2-(4-氯苯基)-2-(1H-1，2，4-三唑基甲基)己腈粗品24克(含量74.88％)。
Claims (1)
1.农用杀菌剂腈菌唑的制备方法，以对氯苯乙腈为原料，在相转移催化剂四乙基溴化铵存在下加入卤代正丁烷并滴加氢氧化钠，反应得2-(4-氯苯基)己腈，其特征是在2-(4-氯苯基)己腈中加入1～5倍(重量计)溶剂二甲基亚砜及过量氢氧化钠或氢氧化钾，搅拌下缓缓加入与2-(4-氯苯基)己腈等摩尔量的氯甲基三唑盐酸盐，反应温度为10～30℃，反应至2-(4-氯苯基)己腈消失，加过量水搅拌，用氯仿萃取后蒸馏脱溶剂得腈菌唑。
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| Application Number | Priority Date | Filing Date | Title |
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| CN94111446A CN1055609C (zh) | 1994-09-22 | 1994-09-22 | 农用杀菌剂腈菌唑的制备方法 |
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| CN94111446A CN1055609C (zh) | 1994-09-22 | 1994-09-22 | 农用杀菌剂腈菌唑的制备方法 |
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| CN1055609C true CN1055609C (zh) | 2000-08-23 |
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| CN100348104C (zh) * | 2003-09-10 | 2007-11-14 | 西安克胜新依达农药有限公司 | 一种腈菌唑水分散性粒剂 |
| CN101538250B (zh) * | 2009-04-09 | 2012-03-07 | 湖北仙隆化工股份有限公司 | 腈菌唑原药的制备方法 |
| CN102060791B (zh) * | 2010-12-17 | 2012-12-26 | 张家港瀚康化工有限公司 | 三唑类杀菌剂腈菌唑的制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4225732A (en) * | 1977-12-22 | 1980-09-30 | General Electric Company | Selective ortho-alkylation of phenolic compounds with an alkane in the presence of a supported nickel oxide catalyst |
| EP0060223A2 (de) * | 1981-03-10 | 1982-09-15 | Ciba-Geigy Ag | Mikrobizide Mittel |
| EP0063099A2 (de) * | 1981-03-10 | 1982-10-20 | Ciba-Geigy Ag | Verfahren zur Herstellung von Phenyläthyltriazolen |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4225732A (en) * | 1977-12-22 | 1980-09-30 | General Electric Company | Selective ortho-alkylation of phenolic compounds with an alkane in the presence of a supported nickel oxide catalyst |
| EP0060223A2 (de) * | 1981-03-10 | 1982-09-15 | Ciba-Geigy Ag | Mikrobizide Mittel |
| EP0063099A2 (de) * | 1981-03-10 | 1982-10-20 | Ciba-Geigy Ag | Verfahren zur Herstellung von Phenyläthyltriazolen |
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