CN106432015B

CN106432015B - The method of overcritical chloromethanes synthesis THIOANISOLE

Info

Publication number: CN106432015B
Application number: CN201610800813.8A
Authority: CN
Inventors: 樊彬; 廖祖态; 陶明; 陈育亮
Original assignee: JIANGXI RENMING PHARMACEUTICAL CHEMICAL INDUSTRY Co Ltd
Current assignee: Jiangxi Yang Fan New Material Co., Ltd.
Priority date: 2016-09-05
Filing date: 2016-09-05
Publication date: 2018-01-26
Anticipated expiration: 2036-09-05
Also published as: CN106432015A

Abstract

The present invention relates to using method of the chloromethanes as methylating reagent synthesis THIOANISOLE, more particularly to using benzenethiol sodium, chloromethanes as raw material, in high-pressure reactor, make chloromethanes in the supercritical state with benzenethiol sodium haptoreaction, the mol ratio of benzenethiol sodium and chloromethanes is 1: 1~1: 10, reaction temperature is 145 DEG C~300 DEG C, and reaction pressure is 6.7~25MPa, and the reaction time is 1~15 hour.After the completion of reaction, reactant mixture is washed with water, collects oil phase, rectification under vacuum, collects (10mmHg, 67 69 DEG C) cut.

Description

The method of overcritical chloromethanes synthesis THIOANISOLE

Technical field

The present invention relates to synthesize THIOANISOLE (also known as thioanisole) as methylating reagent using overcritical chloromethanes Method.

Background technology

THIOANISOLE is colourless transparent liquid, not soluble in water, is soluble in acetone and other organic solvent, its structural formula such as formula S-1 It is shown.THIOANISOLE is widely used, can be as the raw material for synthesizing antibiotic rofecoxib of new generation, and synthetic pesticide, kills The intermediate of the agricultural chemicals such as microbial inoculum, there is important researching value.

THIOANISOLE is mainly synthesized by the methylation reaction of benzenethiol at present.The methylating reagent of document report is main Using dimethyl suflfate (Phosphorus, Sulfur and Silicon and the Related Elements, 180 (7), 1701-1712；2005), dimethyl carbonate (Green Syntheses Series, 1,123-132；2014), iodomethane (Journal ofthe Iranian Chemical Society, 6 (4), 749-753；And methanol (Kokai Tokkyo 2009) Koho, JP2002-371056A, 26Dec 2002).Wherein, dimethyl suflfate as the method for methylating reagent due to toxicity Greatly, atom utilization is low, has been phased out；And although dimethyl carbonate toxicity is smaller, it is low to still suffer from atom utilization, The problems such as use cost is higher；Although iodomethane is fine as the scheme works of methylating reagent, more than 95% can be reached Yield, but because the toxicity of iodomethane is big, price is high, it is not particularly suited for industrialized production scheme；Methanol is above-mentioned four kinds of sides Most suitable methylating reagent in case, document report is using activated alumina as catalyst, in fixed bed reactors, benzene sulphur The methylation reaction of phenol can reach more than 97% yield, but because reaction raw materials benzenethiol contains element sulphur, can be to one As catalyst cause toxic reaction and reduce catalytic activity, therefore, catalyst stability whether can guarantee that be above-mentioned reaction whether There is a deciding factor of real value, and document and undeclared this point, therefore it is considered that the catalytic methylation synthesis of methanol THIOANISOLE method is not fully reliable.

Analysis based on more than, it is believed that current THIOANISOLE synthetic schemes has the problem of respective, therefore, finds It is significant that a kind of high income, environment influence production of the synthesis technique small, cost is low to THIOANISOLE.

The content of the invention

The technical problem to be solved in the present invention is to provide a kind of synthetic method of THIOANISOLE, in the present invention, with benzene sulphur Phenol sodium is raw material, and it is methylating reagent and solvent that chloromethanes, which doubles as,.Chloromethanes is the important by-products in glyphosate production, yield Greatly, it is cheap.The current document report still rarely having by the use of chloromethanes as methylating reagent synthesis THIOANISOLE, its reason are main It is because the methylation activity of chloromethanes is too low, benzenethiol in high yield can not be realized with the cheap reagent under normal conditions Sodium methylation reaction.Therefore, applicant employs process intensification technology, i.e., promotes benzenethiol sodium with overcritical chloromethanes system Methylation reaction.Inventors be surprised to learn that the protrusion solubility property of overcritical chloromethanes, can effectively dissolve raw material benzenethiol Sodium and reaction product etc., and with the reactivity improved extremely, realize good reaction effect.Using the side of the present invention Method synthesis THIOANISOLE has the advantages that simple to operate, high income, post processing are simple, and products therefrom purity is high.

The synthetic method of THIOANISOLE provided by the invention, comprises the following steps：Using benzenethiol sodium, chloromethanes as raw material, In high-pressure reactor, chloromethanes is set with benzenethiol sodium haptoreaction, to obtain THIOANISOLE in the supercritical state.

In a preferred scheme, benzenethiol or the mol ratio of its alkali metal salt and chloromethanes are 1: 1~1: 10, are preferably 1: 2~1: 5.

In another preferred embodiment, described reaction temperature be 145 DEG C~300 DEG C, preferably 145 DEG C~250 DEG C, more Preferably 145 DEG C~200 DEG C, more preferably 145 DEG C~180 DEG C.

In another preferred embodiment, described reaction pressure is 6.7~25MPa, preferably 6.7~20MPa, more preferably For 6.7~15MPa, more preferably 7.7~10.5MPa.

In another preferred embodiment, the described reaction time is 1~15 hour, preferably 3~7 hours.

In another preferred embodiment, described reaction temperature be 145 DEG C~180 DEG C, reaction pressure be 7.7~ 10.5MPa, reaction time are 3~7 hours.

In another preferred embodiment, further comprise reactant mixture is washed with water after the completion of reaction and rectifying Step.

In another preferred embodiment, described rectifying is rectification under vacuum.

In another preferred embodiment, after the completion of reaction, it is washed with water reactant mixture, collects oil phase, rectification under vacuum, (10mmHg, 67-69 DEG C) cut is collected, obtains THIOANISOLE product.

In a specific embodiment, comprise the following steps：

Using benzenethiol sodium, chloromethanes as raw material, wherein benzenethiol sodium: chloromethanes=1: 2~1: 5 (mol ratios), in titanium Reacted in autoclave, reaction temperature is 145 DEG C~180 DEG C, and reaction pressure is 7.7~10.5MPa, and the reaction time is 3~7 Hour.After reaction terminates, with 200mL*3 deionized water washing reaction mixture, the direct rectification under vacuum of oil phase is collected, is collected (10mmHg, 67-69 DEG C) cut is product, and >=98.1%, purity is >=99.1% for yield.

Preparing THIOANISOLE using the method for the present invention has advantages below：

1) using chloromethanes as methylating and solvent, the value of chloromethanes, consumption glyphosate life can effectively be lifted The accessory substance of production process, reduces environmental pollution, and reduces process costs；

2) utilization of supercritical process condition so that the solubility of reaction raw materials (particularly thiophenol sodium), and chlorine can be lifted The reactivity of methane, reach reaction in high yield.

In summary, the present invention is that one kind uses overcritical chloromethanes (143.8 DEG C of critical-temperature, critical pressure Methylating reagent and solvent 6.68MPa) are used as, makes benzenethiol sodium that the new method that S methylation reactions prepare THIOANISOLE occur, instead Equation is answered as shown in S-2.The present invention has cost of material is low, easy to operate, high income, post processing are simple, green etc. Advantage.

Brief description of the drawings

The embodiment of the present invention is described in further detail below in conjunction with the accompanying drawings.

Fig. 1 is THIOANISOLE of the present invention¹H NMR spectras.

Embodiment

Embodiment 1：A kind of synthetic method of THIOANISOLE, carries out following steps successively：

132.2g (1.0mol) benzenethiol sodium is added to 250ml titanium autoclave (band mechanical agitation, temperature probe, electricity Heating mantle, cooling coil, bottom insert canal, atmospheric valve and safety valve) in, nitrogen displacement is vented afterwards three times, then using plunger pump from Bottom insert canal adds 111g (2.0mol) chloromethanes, is heated to 145 DEG C, now pressure is 7.7MPa.Keep the thermotonus 7 hours After terminate to react, be cooled to room temperature, unnecessary chloromethanes (recyclable) released by atmospheric valve, to reaction system normal pressure.Open Autoclave, with 200mL*3 deionized water washing reaction mixture, merge the direct rectification under vacuum of oil phase collected and washed three times, (10mmHg, 67-69 DEG C) cut 121.9g is collected, as product THIOANISOLE, yield 98.1%, gas chromatographic detection purity is 99.1%.

Remarks explanation：Reactant is solidliquid mixture after being cooled to room temperature, and after scrubbed, solid sodium chloride is dissolved in deionization Water, mixture become water phase and an oil phase.

Embodiment 2：A kind of synthetic method of THIOANISOLE, carries out following steps successively：

The titanium autoclave that 66.1g (0.5mol) benzenethiol sodium is added to 250ml (adds with mechanical agitation, temperature probe, electricity Hot jacket, cooling coil, bottom insert canal, atmospheric valve and safety valve) in, nitrogen displacement is vented afterwards three times, then using plunger pump from insert Bottom tube adds 75.8g (1.5mol) chloromethanes, is heated to 160 DEG C, now pressure is 8.9MPa.Keep the thermotonus 5 hours After terminate to react, be cooled to room temperature, unnecessary chloromethanes (recyclable) released by atmospheric valve, to reaction system normal pressure.Open Autoclave, with 200mL*3 deionized water washing reaction mixture, merge the direct rectification under vacuum of oil phase collected and washed three times, (10mmHg, 67-69 DEG C) cut 61.2g is collected, as product THIOANISOLE, yield 98.6%, gas chromatographic detection purity is 99.2%.

Embodiment 3：A kind of synthetic method of THIOANISOLE, carries out following steps successively：

33.0g (0.25mol) benzenethiol sodium is added to 250ml titanium autoclave (band mechanical agitation, temperature probe, electricity Heating mantle, cooling coil, bottom insert canal, atmospheric valve and safety valve) in, nitrogen displacement is vented afterwards three times, then using plunger pump from Bottom insert canal adds 63.1g (1.25mol) chloromethanes, is heated to 180 DEG C, now pressure is 10.5MPa.Keep the thermotonus 3 Terminate reaction after hour, be cooled to room temperature, unnecessary chloromethanes (recyclable) released by atmospheric valve, to reaction system normal pressure. Autoclave is opened, with 200mL*3 deionized water washing reaction mixture, merges the oil phase that collection is washed three times and directly depressurizes essence Evaporate, collect (10mmHg, 67-69 DEG C) cut 61.1g, as product THIOANISOLE, yield 98.4%, gas chromatographic detection purity For 99.2%.

Comparative example 1：Benzenethiol sodium in embodiment 2 is replaced with into benzenethiol and sodium hydroxide, mole is constant (will 0.5mol benzenethiol sodium replaces with 0.5mol benzenethiol+0.5mol sodium hydroxides), remaining is equal to embodiment 2, and final gained is tied Fruit is as shown in table 1 below sequence number 1.

Comparative example 2：Benzenethiol sodium in embodiment 2 is replaced with into benzenethiol and sodium methoxide, mole is constant (will 0.5mol benzenethiol sodium replaces with 0.5mol benzenethiol+0.5mol sodium methoxides), remaining is equal to embodiment 2, final acquired results As shown in table 1 below sequence number 2.

The comparative example experimental conditions of table 1

Sequence number	THIOANISOLE yield, %	THIOANISOLE purity, %	Reacting phenomenon
				1	84.5	99.1	Course of reaction pressure is close with embodiment 2
2	72.3	99.1	Course of reaction pressure is higher than embodiment 2

The reason for analytical table 1, may be as follows：In comparative example 1, the addition of sodium hydroxide result in the generation of water, can lead The hydrolysis of chloromethanes is caused, causes the decline of product yield；In comparative example 2, sodium methoxide can directly react generation diformazan with chloromethanes Ether, cause course of reaction pressure to rise, and significantly reduce product yield.

Finally, it is also necessary to it is noted that listed above is only several specific embodiments of the invention.Obviously, this hair It is bright to be not limited to above example, there can also be many deformations.One of ordinary skill in the art can be from present disclosure All deformations for directly exporting or associating, are considered as protection scope of the present invention.

Claims

A kind of 1. method of overcritical chloromethanes synthesis THIOANISOLE, it is characterized in that comprising the following steps：With benzenethiol sodium, chloromethane Alkane is raw material, in high-pressure reactor, chloromethanes with benzenethiol sodium haptoreaction, is obtained C10H8OS3 in the supercritical state Ether, wherein, described reaction temperature is 145 DEG C~300 DEG C, and reaction pressure is 6.7~25MPa.
2. the method according to claim 11, it is characterized in that：The mol ratio of benzenethiol sodium and chloromethanes is 1: 1~1: 10.
3. the method according to claim 11, it is characterized in that：The mol ratio of benzenethiol sodium and chloromethanes is 1: 2~1: 5.
4. according to the method described in claim any one of 1-3, it is characterized in that：Reaction temperature is 145 DEG C~250 DEG C.
5. according to the method described in claim any one of 1-3, it is characterized in that：Reaction temperature is 145 DEG C~200 DEG C.
6. according to the method described in claim any one of 1-3, it is characterized in that：Reaction temperature is 145 DEG C~180 DEG C.
7. according to the method described in claim any one of 1-3, it is characterized in that：Reaction pressure is 6.7~20MPa.
8. according to the method described in claim any one of 1-3, it is characterized in that：Reaction pressure is 6.7~15MPa.
9. according to the method described in claim any one of 1-3, it is characterized in that：Reaction pressure is 7.7~10.5MPa.
10. according to the method described in claim any one of 1-3, it is characterized in that：Reaction time is 1~15 hour.
11. according to the method described in claim any one of 1-3, it is characterized in that：Reaction time is 3~7 hours.
12. according to the method described in claim any one of 1-3, it is characterized in that：Reaction temperature is 145 DEG C~180 DEG C, reaction pressure Power is 7.7~10.5MPa, and the reaction time is 3~7 hours.
13. according to the method described in claim any one of 1-3, it is characterized in that：Further comprise after the completion of reaction to reaction Mixture is washed with water and the step of rectifying.
14. according to the method for claim 13, described rectifying is rectification under vacuum.
15. according to the method for claim 13, it is characterized in that, after the completion of reaction, reactant mixture is washed with water, collect Oil phase, rectification under vacuum, the cut that pressure is 10mmHg and temperature is 67-69 DEG C is collected, obtains THIOANISOLE product.