CN110963979A

CN110963979A - Synthesis method of oxathioethers

Info

Publication number: CN110963979A
Application number: CN201911318122.4A
Authority: CN
Inventors: 甘秀海; 宋宝安; 朱灵志; 胡德禹; 吴剑; 张建; 陈吉祥
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2019-12-19
Filing date: 2019-12-19
Publication date: 2020-04-07

Abstract

The invention discloses a synthetic method of oxa-linear thioether, which takes p-fluorocinnamic acid as an initial raw material, is activated by N, N-carbonyl-diimidazole, and reacts with hydrazine hydrate to generate p-fluorocinnamic hydrazide, and the p-fluorocinnamic hydrazide reacts with KOH and carbon disulfide to generate (E) And (2) etherifying the intermediate with diethyl sulfate under an alkaline condition to generate crude oxalinear thioether, and finally recrystallizing with ethanol to obtain the target compound. The invention has the advantages of high product yield, high purity, low production cost, safety and environmental protection.

Description

Synthesis method of oxathioethers

Technical Field

The invention belongs to the technical field of chemical industry, and particularly relates to a synthetic method of oxasulfide.

Background

The plant root-knot nematode (Meloidogyne) is one of the plant nematodes which cause serious harm to global crops, can parasitize roots of various hosts such as vegetables, food crops, fruit trees and the like, absorbs nutrient substances to ensure that the hosts lack nutrition and reduce yield, and has more than 1000 billion dollars of agricultural loss caused by the root-knot nematode in the global range according to incomplete statistics. At present, chemical prevention and control are the main methods for preventing and controlling nematode diseases, and various nematocides are used for preventing and controlling the harm of the nematode to crops.

The oxathiane sulfide (named as No. (2018)) No. 059 in agricultural standard words is a nematicide independently developed by Guizhou university, has obvious killing activity on root-knot nematodes, has low toxicity, and provides a high-efficiency and low-risk medicament for preventing and treating crop root-knot nematode diseases.

At present, the synthesis of oxathian sulfide, inventor Songbaoan, Chengyongzhong, Chengyouxiang, Wangbuijiao, Wangzhen treasure, Zhou Dai, Ganhuahai, Chinese patent publication No. CN106674147A discloses a styryl-containing 1,3, 4-oxadiazole sulfide compound, a preparation method and application thereof, wherein the preparation method comprises the steps of (1) taking acetonitrile as a solvent, (E) -p-fluorocinnamic acid, HOBt and EDCI, and then reacting with hydrazine hydrate to prepare hydrazide with the yield of 78.1%; step (2), using absolute ethyl alcohol as a solvent, directly carrying out reflux reaction on (E) -p-fluorocinnamic acid hydrazide, KOH and carbon disulfide, pouring a reaction system into water, adjusting the pH value to 6 by using dilute hydrochloric acid, carrying out suction filtration, and recrystallizing and purifying a crude product by using absolute ethyl alcohol to obtain the yield of 81.0%; and (3) adding 5- (4-fluorostyryl) -1,3, 4-oxadiazole-2-thiol into NaOH aqueous solution, and etherifying with diethyl sulfate to obtain the target compound with the yield of 78.0%. ". Wherein: the yield in the step (1) is not high, the condensing agents HOBt and EDCI are high in price, a large amount of ethyl acetate needs to be obtained, and the post-treatment is complicated; the yield is not ideal, and a large amount of waste water is generated; the yield of (3) is low, and a large amount of wastewater is generated. Therefore, in the preparation method of the patent, the total yield of three-step reaction is lower than 70%, meanwhile, the condensing agents HOBt and EDCI are high in price, in addition, the post-treatment is complicated, and in addition, a large amount of waste water is generated in the process, so that the preparation method is not suitable for industrial mass production.

Disclosure of Invention

The invention aims to overcome the defects and provide a safe and environment-friendly synthetic method of oxasulfide, which has the advantages of high product yield, high purity, low production cost.

The invention relates to a synthetic method of oxasulfide, which comprises the following synthetic route:

(1) synthesis of p-fluorocinnamic hydrazide (E1)

Adding 6.02mol of p-fluorocinnamic acid (E0), 6.02mol of N, N-carbonyl-diimidazole (CDI) and 8-10L of dichloromethane into a reaction kettle, stirring at room temperature until a large amount of white precipitate is generated, cooling to 5 ℃ after the reaction is finished, slowly dropwise adding 9.03-15.05mol of 80% hydrazine hydrate solution, regulating to be neutral by using 1% HCl aqueous solution after the reaction is finished for 1h, and recovering an organic phase to obtain E1;

(2) synthesis of (E) -5- (4-fluorophenylvinyl) -1,3, 4-oxadiazole-2-thiol potassium salt (E2)

Dissolving 6.10-8.32mol of KOH in 6-10L of ethanol under stirring, slowly adding 5.55-8.32mol of carbon disulfide, adding 5.55mol of E1 after a large amount of yellow solid is generated, controlling the temperature to be 40-50 ℃, reacting for 1-2h, and refluxing for 6-10 h. Recovering solvent under reduced pressure to obtain yellow E2 product;

(3) synthesis of oxathioethers (E3)

Adding 3.84mol of E2 and 6L of water into a three-neck flask, dropwise adding 4.61-5.76mol of diethyl sulfate, controlling the temperature to be 20-30 ℃, controlling the pH value to be 8-10 in the reaction process, and reacting for 8-10 h. After the reaction is finished, filtering and washing for 2 times to obtain a target product E3.

Compared with the prior art, the invention has obvious beneficial effects, and the technical scheme can show that: the synthesis of the oxalinear thioether provided by the invention is characterized in that p-fluorocinnamic acid (E0) is used as an initial raw material, activated by N, N-carbonyl-diimidazole, and reacts with hydrazine hydrate to generate an intermediate p-fluorocinnamic hydrazide (E1), the intermediate E1 reacts with KOH and carbon disulfide to generate (E) -5 (4-fluorostyryl) -1,3, 4-oxadiazole-2-thiol potassium salt (E2), the intermediate is etherified with diethyl sulfate under an alkaline condition to generate a crude oxalinear thioether, and finally, the crude oxalinear thioether is recrystallized by ethanol to obtain a target compound. The method has the advantages of simple synthesis operation, high product yield, high purity, low production cost, reduction of discharge of a large amount of waste water, safety, environmental protection and suitability for industrial production.

Detailed Description

Example 1:

a synthetic method of oxasulfide comprises the following steps:

(1) synthesis of p-fluorohydrazide (E1): adding p-fluorocinnamic acid (1kg, 6.02mol), CDI (975.93g, 6.02mol) and dichloromethane (8L) into a 20L reaction kettle, stirring at room temperature until a large amount of white precipitate is generated, reacting for about 30min, cooling to 5 ℃, slowly dropwise adding 80% hydrazine hydrate (753.24g, 12.04mol) solution, adjusting to neutrality by using 1% HCl aqueous solution after 1h is finished, and recovering an organic phase to obtain 1021g E1, wherein the yield is 94% and the purity is 90%.

(2) Synthesis of (E) -5- (4-fluorophenylvinyl) -1,3, 4-oxadiazole-2-thiol potassium salt (E2): 373.66g KOH (6.66mol) was dissolved in 6L ethanol with stirring, 633.78g carbon disulphide (8.32mol) was added slowly to give a large amount of yellow solid, after which 1kg E1(5.55mol) was added, the temperature was controlled at 40 ℃ and the reaction was carried out for 2h and then under reflux for 8 h. The solvent was recovered under reduced pressure to give 1332g of yellow E2 product in 92% yield and 85% purity.

(3) Synthesis of oxasulfide (E3): 1kg of E2(3.84mol) is added into a 20L three-necked bottle, 6L of water is added, 769.93g (4.99mol) of 1.3 equivalent of diethyl sulfate is added dropwise, the temperature is controlled at 30 ℃, the PH value is controlled at 8 in the reaction process, and the reaction lasts 8 hours. The mixture is filtered and washed by water for 2 times to obtain 895g of target product E3, the yield is 93 percent, and the purity is 92 percent.

Example 2:

a synthesis process of oxasulfide comprises the following steps:

(1) synthesis of p-fluorohydrazide (E1): adding p-fluorocinnamic acid (1kg, 6.02mol), CDI (975.93g, 6.02mol) and dichloromethane (10L) into a 20L reaction kettle, stirring at room temperature until a large amount of white precipitate is generated, reacting for about 20min, cooling to 5 ℃, slowly dropwise adding 80% hydrazine hydrate (941.55g, 15.05mol) solution, adjusting to neutrality by 1% HCl aqueous solution after reaction for 2h, and recovering an organic phase to obtain 1005g E1 with the yield of 92% and the purity of 93%.

(2) Synthesis of (E) -5- (4-fluorophenylvinyl) -1,3, 4-oxadiazole-2-thiol potassium salt (E2): 342.52g KOH (6.10mol) was dissolved in 6L ethanol with stirring, 507.03g (6.66mol) carbon disulphide was slowly added to form a large amount of yellow solid, then 1kg E1(5.55mol) was added, the temperature was controlled at 50 ℃ and the reaction was carried out for 2h, followed by refluxing for 6 h. The solvent was recovered under reduced pressure to give 1302g of yellow E2 product in 90% yield and 92% purity.

(3) Synthesis of oxasulfide (E3): 1kg of E2(3.84mol) is added into a 20L three-necked bottle, 6L of water is added, 710.70g (4.61mol) of 1.2 equivalent of diethyl sulfate is added dropwise, the temperature is controlled at 20 ℃, the pH value is controlled to 10 in the reaction process, and the reaction is carried out for 10 hours. Filtering and washing for 2 times to obtain 875g of a target product E3 with the yield of 91 percent and the purity of 90 percent.

Example 3:

a synthesis process of oxasulfide comprises the following steps:

(1) synthesis of p-fluorohydrazide (E1): adding p-fluorocinnamic acid (1k g, 6.02mol), CDI (975.93g, 6.02mol) and dichloromethane (8L) into a 20L reaction kettle, stirring at room temperature until a large amount of white precipitate is generated, reacting for about 30min, cooling to 5 ℃, slowly dropwise adding 80% hydrazine hydrate (564.93g, 9.03mol) solution, adjusting to neutrality by 1% HCl aqueous solution after 1h is finished, and recovering an organic phase to obtain 1016g E1 with the yield of 93% and the purity of 91%.

(2) Synthesis of (E) -5- (4-fluorophenylvinyl) -1,3, 4-oxadiazole-2-thiol potassium salt (E2): 467.07g KOH (8.32mol) was dissolved in 10L ethanol with stirring, 633.78g (5.55mol) carbon disulphide was slowly added to form a large amount of yellow solid, then 1kg E1(5.55mol) was added, the temperature was controlled at 50 ℃ and the reaction was carried out for 2h, followed by reflux for 10 h. The solvent was recovered under reduced pressure to give 1361g of yellow E2 product in 94% yield and 91% purity.

(3) Synthesis of oxasulfide (E3): 1kg of E2(3.84mol) is added into a 20L three-necked bottle, 6L of water is added, 888.38g (5.76mol) of 1.5 equivalent of diethyl sulfate is added dropwise, the temperature is controlled at 30 ℃, the pH value is controlled at 9 in the reaction process, and the reaction is carried out for 10 hours. The mixture is filtered and washed by water for 2 times to obtain 897g of target product E3, the yield is 93 percent, and the purity is 92 percent.

The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and any simple modification, equivalent change and modification made to the above embodiment according to the technical spirit of the present invention are within the scope of the present invention without departing from the technical spirit of the present invention.

Claims

1. A synthetic method of oxasulfide comprises the following synthetic route:

(1) synthesis of p-fluorocinnamic hydrazide (E1)

（2）（E) Synthesis of (E) potassium (E2) 5- (4-fluorophenylvinyl) -1,3, 4-oxadiazole-2-thiol

(3) Synthesis of oxathioethers (E3)

。

2. The method of claim 1, wherein the method comprises the following steps:

(1) synthesis of p-fluoro-cinnamoyl hydrazide

Adding 6.02mol of p-fluorocinnamic acid, 6.02mol of N, N-carbonyl-diimidazole and 8-10L of dichloromethane into a reaction kettle, stirring at room temperature until a large amount of white precipitate is generated, cooling to 5 ℃ after the reaction is finished, slowly dropwise adding 9.03-15.05mol of 80% hydrazine hydrate solution, adjusting to be neutral by using 1% HCl aqueous solution after 1h is finished, and recovering an organic phase to obtain p-fluorocinnamic hydrazide;

（2）（E) Synthesis of potassium (E) -5- (4-fluorophenylethenyl) -1,3, 4-oxadiazole-2-thiol

Dissolving 6.10-8.32mol of KOH in 6-10L of ethanol under stirring, slowly adding 5.55-8.32mol of carbon disulfide to generate a large amount of yellow solidAdding 5.55mol of p-fluoro-cinnamoylhydrazide, controlling the temperature to be 40-50 ℃, reacting for 1-2h, refluxing for 6-10h, and recovering the solvent under reduced pressure to obtain yellow (E) -5- (4-fluorophenylvinyl) -1,3, 4-oxadiazole-2-thiol potassium salt product;

(3) synthesis of oxathioethers

3.84mol of (A) are added into a three-mouth bottleE) 5- (4-fluorostyryl) -1,3, 4-oxadiazole-2-thiol potassium salt and 6L of water, dropwise adding 4.61-5.76mol of diethyl sulfate, controlling the temperature to be 20-30 ℃, controlling the pH value to be 8-10 in the reaction process, reacting for 8-10h, filtering after the reaction is finished, and washing with water for 2 times to obtain the oxa-linear thioether.