CN102391307A - Synthesization method of Dufulin - Google Patents
Synthesization method of Dufulin Download PDFInfo
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- CN102391307A CN102391307A CN2011103443262A CN201110344326A CN102391307A CN 102391307 A CN102391307 A CN 102391307A CN 2011103443262 A CN2011103443262 A CN 2011103443262A CN 201110344326 A CN201110344326 A CN 201110344326A CN 102391307 A CN102391307 A CN 102391307A
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Abstract
The invention relates to a synthesization method of Dufulin. In the preparation method, 2-ammonia-4-methyl benzothiazole, fluorobenzaldehyde and diethyl phosphite are taken as materials and the Dufulin is obtained by two steps of heating reaction under the condition of catalysts. The method is short in process, little in waste discharge and beneficial to industrial production.
Description
Technical field
The present invention relates to produce the method for malicious fluorine phosphorus
Background technology
In recent years various crop virosis present serious development trend, except tobacco mosaic disease, cucumber mosaic virus and tomato virus disease that tradition comparatively generally takes place.The rice stripe leaf is withered, rice black-streaked dwarf, southern rice black-streaked dwarf, and morbidity is Exponential growth.Special southern rice black-streaked dwarf, since calendar year 2001 first after Yangxi County, Guangdong finds, in Guangdong generation is arranged year after year; After 2003, Hainan also takes place year after year; 2008 in Guangdong, ground such as Guangxi, Hainan, Hunan, Jiangxi, Anhui finds that all only partial area are injured seriously.2009, south China 9 provinces and regions took place, and about 2,000,000 mu of injured area, part field piece lose to be received, and loses about 70,000 tons.2010, this disease seriously took place in China 11 provinces, about 1,800 ten thousand mu of area.Infecting of this disease can cause serious production loss, even large stretch of total crop failure, therefore controls the expansion of disease, and guarantees that output is very important and instant.
Poison fluorine phosphorus is that China independently formulates new drug, and the Department of Science and Technology lists country's 15 emphasis tackling key problem initiative new varieties of pesticides in.Check and accept through " 15 " State Commission for Restructuring the Economic Systems special topic, be chosen as outstanding.Through our a large amount of experiment, show that malicious fluorine phosphorus can effectively prevent and delay the generation and the expansion of rice black-streaked dwarf virus disease, tobacco mosaic disease, tomato virus disease etc.
Chemistry N-[2-(the 4-methylbenzothiazole base)] by name-2-amino-2-fluoro phenyl-O of poison fluorine phosphorus, the O-diethyl phosphonate, structural formula is as follows:
The pure article of poison fluorine phosphorus are clear crystal, and molecular formula is C
19H
22FN
2O
3PS, molecular weight are 408.43
Its fusing point is 143～145 ℃.Be soluble in organic solvents such as acetone, THF, DMSO 99.8MIN., 22 ℃ of solubleness in water, acetone, hexanaphthene, pimelinketone and YLENE are respectively 0.04g/L, 147.8g/L, 17.28g/L, 329.00g/L, 73.30g/L.Poison fluorine phosphorus is all more stable to light, heat and humidity, decomposes gradually when meeting bronsted lowry acids and bases bronsted lowry.
Poison fluorine phosphorus is a kind of alpha-amino group SULPHOSUCCINIC ACID ESTER; Can type of employing Mannieh type synthesis method; This method is divided into Kabachnik-Fields one-step synthesis (aldehyde, amine, the reaction of phosphorous acid ester one kettle way) and two kinds of methods of two step synthesis methods (the reaction dehydration earlier of aldehyde and amine generates imines, again with phosphorous acid ester generation nucleophilic addition) again.Because the single stage method reaction conditions is restive, how to carry out a spot of synthesizing in the laboratory,
The two step methods that adopt synthetic more in the industry.Patent CN 1291993C adopts the synthetic malicious fluorine phosphorus of two-step approach, and the first step generates product through after purifying, the reaction in following step; But its first step reaction conversion ratio is very low, and the two-step reaction total recovery is very low, and unreacted starting material can not get into next step reaction, causes raw-material waste, and yield is lower.
The present invention has gathered the advantage of single stage method and two-step approach, adopts two step one kettle ways, and the unreacted starting material of the first step still can continue reaction in second step, and uses catalyzer that the yield of synthetic malicious fluorine phosphorus is improved greatly.
Summary of the invention
The technology that the purpose of this invention is to provide a kind of efficient, economic, easy synthetic malicious fluorine phosphorus.
A kind of method of synthetic malicious fluorine phosphorus at first with adjacent fluorobenzaldehyde and 2-ammonia-4-methylbenzothiazole catalysis reacting by heating, adds diethyl phosphite then again in same reaction vessel, continue heating and obtain malicious fluorine phosphorus.
Preferably, said raw material have solvent or solvent-free in the presence of, catalysis heating prepares malicious fluorine phosphorus; Wherein solvent is one or more in toluene, YLENE, tetracol phenixin, chloroform, the benzene; Catalyzer is one or more in tosic acid, thionamic acid, acetic acid, the sulfuric acid.
Preferably, each quality of material ratio is: 2-ammonia-4-methylbenzothiazole: adjacent fluorobenzaldehyde: diethyl phosphite=1: (0.4-1.5): (0.7-2), Heating temperature is 50-180 ℃.
Wherein, to add the first step reaction of pining for be 0.5-10 hour heat-up time to two-step catalysis; It is 2-10 hour that second step was reacted heat-up time.
Preferably, the first step is reacted 3-6 hour heat-up time; It is 2-5 hour that second step was reacted heat-up time.
A kind of compound method of malicious fluorine phosphorus, it is characterized in that adopting adjacent fluorobenzaldehyde, 2-ammonia-4-methylbenzothiazole, diethyl phosphite is raw material, under solvent or condition of no solvent, catalysis adds hot preparation.Wherein solvent is toluene, YLENE, tetracol phenixin, chloroform, benzene, solvent-freely is meant the reaction that does not add under any solvent condition.Catalyzer is tosic acid, acetic acid, thionamic acid (NH
2SO
3H, SA), one or more mixture of catalysts in the sulfuric acid.Adopt two step one kettle ways, each quality of material is than 2-ammonia-4-methylbenzothiazole: adjacent fluorobenzaldehyde: diethyl phosphite=1: (0.4-1.5): (0.7-2), Heating temperature is 50-180 ℃.The employing of two step one kettle ways, raw-material waste has been avoided in the purification of having save the first step.Adopt two step one kettle ways, the first step heat-up time is 0.5-10 hour, and second step reaction heat-up time is 2-10 hour.
This compound method has starting material and is easy to get, and synthetic route is brief, and the three wastes are few, the advantage that yield is high; The catalyzer low price that this compound method adopts, catalytic efficiency (is high; Adopt two step one kettle ways, the first step reaction after product does not need to handle, and can drop into diethyl phosphite and descend the step reaction, and the step that simplifies the operation has improved yield.
Embodiment
The synthetic embodiment of poison fluorine phosphorus:
The invention is not restricted to these disclosed embodiment; The present invention is with the described scope of soverlay technique scheme; And the various distortion of claim scope change with equivalence; Under the prerequisite that does not depart from technical solution of the present invention, any modification or improvement that those skilled in the art that the present invention did are realized easily belong to protection domain of the presently claimed invention.
Raw materials usedly be commercially available analytical pure.
Embodiment 1:
In the 500L enamel reaction still of band division box, add 2-ammonia-4-methylbenzothiazole 40kg, adjacent fluorobenzaldehyde 30kg, catalyzer tosic acid 1kg; Toluene 200kg; Reflux state reaction down adds diethyl phosphite 40kg after about 5 hours, reaction 4h stops.Steaming desolventizes, and is cooled to 70 ℃, adds a certain amount of ethanol, is heated to backflow, keeps reflux state 1h, cools to 20 ℃, keeps stirring 3h.Centrifuging, solid product is dry, get 80kg clear crystal shape poison fluorine phosphorus product, fusing point 144-145 ℃, yield 80%.Its
1H NMR data are as follows:
1.117～1.344(m，6H，2CCH
3)，2.523(s，3H，Ar-CH
3)，3.796～4.062(m，2H，OCH
2)，4.207～4.298(m，2H，OCH
2)，5.834～5.890(d，1H，CHP)，6.946～7.376(m，7H，Ar-H)，7.623～7.660(t，J＝7.2Hz，1H，NH).
Embodiment 2:
In the 500L enamel reaction still of band division box, add 2-ammonia-4-methylbenzothiazole 42kg, adjacent fluorobenzaldehyde 30kg, catalyzer tosic acid 1kg; YLENE 175kg; Reflux state reaction down adds diethyl phosphite 34kg after about 3 hours, react and stopped in 5 hours.Steaming desolventizes, and is cooled to 70 ℃, adds a certain amount of ethanol, is heated to backflow, keeps reflux state 1h, cools to 20 ℃, keeps stirring 3h.Centrifuging, solid product is dry, get 76kg clear crystal shape poison fluorine phosphorus product, fusing point 143-145 ℃, yield 73%.Nuclear magnetic data is with embodiment 1.
Embodiment 3:
In the 500L enamel reaction still of band division box, add 2-ammonia-4-methylbenzothiazole 40kg, adjacent fluorobenzaldehyde 30kg, catalyzer glacial acetic acid 0.8kg, toluene 200kg, reflux state reaction down add diethyl phosphite 40kg after about 4 hours, and reaction 4h stops.Steaming desolventizes, and is cooled to 70 ℃, adds a certain amount of ethanol, is heated to backflow, keeps reflux state 1h, cools to 20 ℃, keeps stirring 3h.Centrifuging, solid product is dry, get 78kg clear crystal shape poison fluorine phosphorus product, fusing point 143-145 ℃, yield 78%.Nuclear magnetic data is with embodiment 1.
Embodiment 4:
In the 1000L enamel reaction still of band division box, add 2-ammonia-4-methylbenzothiazole 60kg, adjacent fluorobenzaldehyde 45kg, catalyzer tosic acid 3kg; Toluene 500kg; Reflux state reaction down adds diethyl phosphite 76kg after about 5 hours, reaction 4h stops.Steaming desolventizes, and is cooled to 70 ℃, adds a certain amount of ethanol, is heated to backflow, keeps reflux state 1h, cools to 20 ℃, keeps stirring 3h.Centrifuging, solid product is dry, get 125kg clear crystal shape poison fluorine phosphorus product, fusing point 143-145 ℃, yield 84%.Nuclear magnetic data is with embodiment 1.
Embodiment 5:
In the 1000L enamel reaction still of band division box, add 2-ammonia-4-methylbenzothiazole 60kg, adjacent fluorobenzaldehyde 45kg, catalyzer thionamic acid 1kg; Toluene 500kg; Reflux state reaction down adds diethyl phosphite 61kg after about 4 hours, reaction 4h stops.Steaming desolventizes, and is cooled to 70 ℃, adds a certain amount of ethanol, is heated to backflow, keeps reflux state 1h, cools to 20 ℃, keeps stirring 3h.Centrifuging, solid product is dry, get 122kg clear crystal shape poison fluorine phosphorus product, fusing point 143-145 ℃, yield 82%.Nuclear magnetic data is with embodiment 1.
Conclusion: the technology that the invention provides a kind of efficient, economic, easy synthetic malicious fluorine phosphorus.
Claims (5)
1. the method for a synthetic malicious fluorine phosphorus is characterized in that at first adjacent fluorobenzaldehyde and 2-ammonia 4-methylbenzothiazole catalysis reacting by heating are added diethyl phosphite then again in same reaction vessel, continues to heat to obtain malicious fluorine phosphorus.
2. method according to claim 1, said starting material have solvent or solvent-free in the presence of, catalysis heating prepares malicious fluorine phosphorus; Wherein solvent is one or more in toluene, YLENE, tetracol phenixin, chloroform, the benzene; Catalyzer is one or more in tosic acid, thionamic acid, acetic acid, the sulfuric acid.
3. method according to claim 1 and 2, it is characterized in that each quality of material ratio is: 2-ammonia-4-methylbenzothiazole: adjacent fluorobenzaldehyde: diethyl phosphite=1: (0.4-1.5): (0.7-2) Heating temperature is 50-180 ℃.
4. method according to claim 1 and 2 is characterized in that it is 0.5-10 hour heat-up time that two-step catalysis adds the first step reaction of pining for; It is 2-10 hour that second step was reacted heat-up time.
5. method according to claim 4 is characterized in that 3-6 hour heat-up time of the first step reaction; It is 2-5 hour that second step was reacted heat-up time.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102626078A (en) * | 2012-04-12 | 2012-08-08 | 广西田园生化股份有限公司 | Ultra-low-volume liquid for preventing and treating plant viral diseases and transmitting media |
| CN102657219A (en) * | 2012-04-12 | 2012-09-12 | 广西田园生化股份有限公司 | Dufulin-containing ultra low volume liquid formulation |
| CN103636670A (en) * | 2012-06-27 | 2014-03-19 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and enestroburin |
| CN103636669A (en) * | 2012-06-27 | 2014-03-19 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and trifloxystrobin |
| CN103636668A (en) * | 2012-06-27 | 2014-03-19 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and orysastrobin |
| CN104886122A (en) * | 2015-06-17 | 2015-09-09 | 广西田园生化股份有限公司 | Compound composition containing dufulin and pyrazole amide bactericide and bactericide |
| CN112500432A (en) * | 2019-09-16 | 2021-03-16 | 华东理工大学 | Dufulin polymorphs and preparation method and application thereof |
| CN114891039A (en) * | 2022-05-17 | 2022-08-12 | 广西田园生化股份有限公司 | Preparation method of Dufulin compound |
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| CN1687088A (en) * | 2005-04-04 | 2005-10-26 | 贵州大学 | N-substituted benzothiazolyl-1-substituted phenyl-0,0-dialkyl-alpha-amino phosphonate ester derivatives preparation and application |
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Patent Citations (1)
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| CN1687088A (en) * | 2005-04-04 | 2005-10-26 | 贵州大学 | N-substituted benzothiazolyl-1-substituted phenyl-0,0-dialkyl-alpha-amino phosphonate ester derivatives preparation and application |
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| 《贵州大学学报（自然科学版）》 20050531 薛伟等 超声辐射下N-（对三氟甲基苯基）-alpha-（间氟苯基）-alpha-氨基膦酸乙酯的合成 第22卷, 第2期 * |
| LINHONG JIN等: "Synthesis, X-ray crystallographic analysis,and antitumor activity of N-(benzothiazole-2-yl)-1-(fluorophenyl)-O,O-dialkyl-a-aminophosphonates", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102626078A (en) * | 2012-04-12 | 2012-08-08 | 广西田园生化股份有限公司 | Ultra-low-volume liquid for preventing and treating plant viral diseases and transmitting media |
| CN102657219A (en) * | 2012-04-12 | 2012-09-12 | 广西田园生化股份有限公司 | Dufulin-containing ultra low volume liquid formulation |
| CN103636670A (en) * | 2012-06-27 | 2014-03-19 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and enestroburin |
| CN103636669A (en) * | 2012-06-27 | 2014-03-19 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and trifloxystrobin |
| CN103636668A (en) * | 2012-06-27 | 2014-03-19 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and orysastrobin |
| CN103636670B (en) * | 2012-06-27 | 2015-04-22 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and enestroburin |
| CN103636668B (en) * | 2012-06-27 | 2015-04-22 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and orysastrobin |
| CN103636669B (en) * | 2012-06-27 | 2015-04-22 | 广西田园生化股份有限公司 | Sterilization composition containing Dufulin and trifloxystrobin |
| CN104886122A (en) * | 2015-06-17 | 2015-09-09 | 广西田园生化股份有限公司 | Compound composition containing dufulin and pyrazole amide bactericide and bactericide |
| CN112500432A (en) * | 2019-09-16 | 2021-03-16 | 华东理工大学 | Dufulin polymorphs and preparation method and application thereof |
| CN114891039A (en) * | 2022-05-17 | 2022-08-12 | 广西田园生化股份有限公司 | Preparation method of Dufulin compound |
| CN114891039B (en) * | 2022-05-17 | 2024-03-29 | 广西田园生化股份有限公司 | Preparation method of Dufulin compound |
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Application publication date: 20120328 |