WO2023010649A1 - Method for continuous synthesis of p-toluenesulfonyl chloride - Google Patents

Abstract

A method for continuous synthesis of p-toluenesulfonyl chloride. Toluene, sulfur trioxide, chlorosulfonic acid, organic bases and a solvent are mixed in a first static mixer and pumped into a first microreactor for reaction. A primary reaction mixture discharged from an outlet of the first microreactor flows into a second static mixer, and is mixed with sulfur trioxide, chlorosulfonic acid, low-carbon chain fatty acid and a solvent that are pumped into the second static mixer respectively. The obtained mixed material is pumped into a second microreactor for reaction. A secondary reaction mixture discharged from the second microreactor is cooled, crystallized and separated to obtain p-toluenesulfonyl chloride as a product. According to the method, the production efficiency can be improved. Due to the addition of a sulfone inhibitor, the problem of easy generation of a large amount of sulfone substances and polysulfonates by sulfur trioxide is effectively solved, and hydrogen chloride gas is prevented from being generated.

Description

Method for continuous synthesis of p-toluenesulfonyl chloride technical field

The invention relates to the technical field of fine chemical intermediates, in particular to a green process for preparing p-toluenesulfonyl chloride by using sulfur trioxide, chlorosulfonic acid, toluene, a catalyst and an inhibitor in a microchannel reactor.

Background technique

The synthetic route of p-toluenesulfonyl chloride mainly uses toluene and chlorosulfonic acid as raw materials, and ammonium chloride, N, N-dimethylacetamide and triethylamine as catalysts to prepare p-toluenesulfonate through sulfonation and acyl chloride reactions. acid chloride. Such as German patent Ger P1172258, Ger p1112978, US patent US3.686.300, Japanese JP Zhao 56-46860. These methods not only need higher reaction temperature (generally 60～90 ℃), but the production efficiency is very low, and at the same time, a large amount of dilute sulfuric acid waste liquid is generated and a large amount of hydrogen chloride gas is generated, which seriously corrodes the equipment and pollutes the environment. The reaction process is precisely controlled, and the yield needs to be improved. The highest yield of US3.686.300 is 83%. Nevertheless, at present, most domestic manufacturers adopt this process route to produce p-toluenesulfonyl chloride, because this process has the characteristics of less operation steps and short reaction cycle. However, due to the limitations of the production process, a large amount of acidic raw materials used in the process, as well as a large amount of hydrogen chloride gas and a large amount of dilute sulfuric acid generated during the reaction severely corrode equipment, the difficulty and cost of treatment are quite high, and the environment is seriously polluted. The yield is lower.

CN107344922A discloses a method for preparing p-toluenesulfonyl chloride. The method is to first add p-toluenesulfonate magnesium into an aprotic polar organic solvent, and then react with a chlorination reagent under an inert atmosphere to prepare p-toluenesulfonyl chloride. CN201310476616.1 discloses a synthesis process of p-toluenesulfonyl chloride, adding chlorosulfonic acid and mixed sulfonation additives in a glass reactor; toluene is added dropwise in three times, and after the dropwise addition, it is kept for 2 hours; then the reaction solution is cooled and vacuum pumped After filtration, solvent extraction, crystallization and drying, p-toluenesulfonyl chloride was obtained. CN102408364A discloses a preparation method of p-toluenesulfonyl chloride, which reacts ammonium toluenesulfonate and bis(trichloromethyl)carbonate (commonly known as "triphosgene") in an inert organic solvent under the condition of an organic base as a catalyst , Synthesis of p-toluenesulfonyl chloride. CN201520995039 reports a production system of p-toluenesulfonyl chloride. The production system includes a sulfonation reactor, a decomposition reactor and a product post-treatment system connected in sequence. The series connection of the reactors does not solve the control in the production process. Problems, serialization problems, productivity problems and "waste acid" problems, it is even more impossible to realize automation.

The processes or production systems disclosed in the above documents can only be improved on the basis of traditional processes, without substantial technological progress. CN101195593 discloses a production process for sulfonating sulfur trioxide and diluent alkylbenzene to obtain alkylbenzenesulfonic acid, and then performing sulfonyl chloride with chlorosulfonic acid to produce alkylbenzenesulfonyl chloride. This production process actually divides a one-step chemical reaction into two steps, especially the separation of sulfones and polysulfides produced during the sulfonation of sulfur trioxide. The intermediate process is complicated, and the diluent recovery and separation process is very long. The efficiency is low, coupled with the structural characteristics of the tubular reactor itself, it is difficult to achieve precise control, and the pollution problem has not been effectively solved.

According to the reaction mechanism of sulfonation and chlorosulfonation, the sulfonation of toluene is closely related to the chlorosulfonation process. Toluene is first sulfonated by a sulfonating agent (sulfonating agent can be sulfur trioxide, high-concentration sulfuric acid or fuming sulfuric acid, chlorosulfonic acid) to generate p-toluenesulfonic acid, and then chlorinated by chlorosulfonic acid to generate p-toluene Sulfonyl chloride. P-toluenesulfonic acid can also react with phosgene, thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, etc. to prepare p-toluenesulfonyl chloride. The shortcoming of these methods is: (1) phosgene in the phosgene method is highly toxic gas, uses unsafe and the raw material cost of thionyl chloride is higher; (2) thionyl chloride method can produce the sulfur dioxide of polluting environment By-products; (3) The by-product phosphorous acid or phosphoric acid generated by the phosphorus oxychloride method or the phosphorus oxychloride method is difficult to remove, which affects product quality. In fact, these acyl chloride reactions are only used for special cases of preparation.

The microchannel reactor is a new type of miniaturized continuous flow pipeline reactor, which is a three-dimensional structural element that can be used for chemical reactions and is manufactured from a solid matrix with the help of special micromachining technology. The microchannels in the reactor are manufactured by precision machining technology, and the characteristic size is generally between 10 and 1000 microns, with channel diversity at the same time. Fluids flow in these channels and desired chemical reactions take place in these channels. The microchannel reactor has a very large specific surface area/volume ratio in the design of the microstructure, resulting in a great mass transfer and heat transfer capacity, and the fundamental advantages brought about by this are extremely high heat exchange efficiency and mixing efficiency. Precise control of reaction temperature, reaction material ratio, and instant mixing are key factors for improving yield, selectivity, safety, and product quality.

In recent years, a lot of research has been carried out at home and abroad, and the microchannel reactor technology has been developed rapidly, making it more and more used in process research and development and industrial production. Microchannel reactors have incomparable characteristics of traditional reactors in organic synthesis. The reaction temperature, reaction time, material ratio and mass transfer rate can be precisely controlled, and the structure is safe and has good operability (microreactor The Application of Technology in Organic Synthesis "Chemical Reagents", Vol. 29, No. 6, June 2007, p. 339). Especially in the field of fine chemical industry, its potential application prospect has been widely recognized by academic circles and business circles (Application of Microreactor Technology in Fine Chemical Industry "Fine Chemical Industry" Volume 32, Issue 1 of 2006). Chen Yanquan and others have studied the sulfonation of toluene with sulfur trioxide in a microchannel reactor to prepare p-toluenesulfonic acid, and have studied the effects of various reaction conditions on the reaction results (toluene liquid phase in the microreactor SO _sulfonate Chemical Process Research "Chemical Reaction Engineering and Technology", Volume 29, Issue 3, 2013, Page 253).

Contents of the invention

The technical problem to be solved in the present invention is to provide a kind of in microchannel reactor (hereinafter referred to as: microreactor), carry out the technique that p-toluenesulfonyl chloride is prepared by the chlorosulfonation of continuous toluene with sulfur trioxide and chlorosulfonic acid.

In order to solve the problems of the technologies described above, the invention provides a method for continuously synthesizing p-toluenesulfonyl chloride, using toluene as a reaction raw material:

1), after toluene, sulfur trioxide, chlorosulfonic acid, organic bases and solvent are mixed in the first static mixer, are pumped into the first microreactor under the effect of constant flow pump one and react (sulfonation reaction );

The reaction temperature in the first microreactor is 10-60°C, and the reaction time is 10-35 minutes;

2), the first reaction mixture discharged from the outlet of the first microreactor flows into the second static mixer, and is pumped into sulfur trioxide, chlorosulfonic acid, low carbon chain fatty acid and solvent in the second static mixer respectively Mixing is carried out in the second static mixer, and the resulting mixed material is pumped into the second microreactor for reaction (sulfonation and chlorosulfonation reaction) under the action of constant flow pump two;

The reaction temperature of the second microreactor is 20～60 ℃, and the reaction time is 10～40 minutes;

Toluene: (the sulfur trioxide entering the first microreactor+the sulfur trioxide entering the second microreactor): (the chlorosulfonic acid entering the first microreactor+the chlorosulfonic acid entering the second microreactor): Organic bases: low carbon chain fatty acids = molar ratio of 1:0.8～1.5:0.8～1.5:0.018～0.022:0.18～0.22;

Enter the sulfur trioxide of the first microreactor: the mol ratio of the sulfur trioxide=(1.5 ± 0.1) that enters the second microreactor: 1;

Enter the chlorosulfonic acid of the first microreactor: the mol ratio of the chlorosulfonic acid=1 that enters the second microreactor: (1 ± 0.1);

3), the secondary reaction mixture discharged from the second microreactor is cooled, crystallized and separated to obtain p-toluenesulfonyl chloride as the product.

In the present invention, the mixture of sulfur trioxide (liquid) and chlorosulfonic acid is used as the chlorosulfonation reagent, the low-carbon chain fatty acid is used as the sulfone substance inhibitor, and the organic bases are used as the sulfonation reaction positioning catalyst, and the positioning catalyst The aim is to minimize the production of o-toluenesulfonyl chloride as a by-product. The reaction of the first microreactor and the reaction of the second microreactor are carried out simultaneously in actual operation.

As the improvement of the method for the continuous synthesis of p-toluenesulfonyl chloride of the present invention:

The organic bases are any of the following: piperazine, tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride, melamine, pyridine, dodecylanilinotrimethylammonium chloride ; preferably pyridine;

The low carbon chain fatty acid is any of the following: acetic acid, propionic acid, isopropionic acid, chloroacetic acid, trifluoroacetic acid; preferably acetic acid, trifluoroacetic acid.

As a further improvement of the method for the continuous synthesis of p-toluenesulfonyl chloride of the present invention:

The sum of the solvent entering the first microreactor and the solvent entering the second microreactor is defined as the total solvent, and 200-300ml of total solvent is used for every 1mol of toluene;

The solvent is any of the following: dichloromethane, chloroform, 1,2-dichloroethane.

As a further improvement of the method for the continuous synthesis of p-toluenesulfonyl chloride of the present invention:

The temperature in the first static mixer is ≤-5°C (generally -10°C～-5°C);

The temperature in the second static mixer is ≤ 25°C (generally 10°C-25°C).

As a further improvement of the method for the continuous synthesis of p-toluenesulfonyl chloride of the present invention:

As preferred:

The reaction temperature in the first microreactor is 20～40 ℃, and the reaction time is 20～33 minutes;

The reaction temperature in the second microreactor is 40～60 ℃, and the reaction time is 23～39 minutes;

Toluene: (the sulfur trioxide entering the first microreactor+the sulfur trioxide entering the second microreactor): (the chlorosulfonic acid entering the first microreactor+the chlorosulfonic acid entering the second microreactor): Organic bases: low-carbon chain fatty acids = molar ratio of 1:1-1.2:0.9-1.0:0.018-0.022:0.18-0.22;

As a further preference:

The reaction temperature in the first microreactor is 25 DEG C, and the reaction time is 20 minutes;

The reaction temperature in the second microreactor is 40 DEG C, and the reaction time is 23 minutes;

Toluene: (the sulfur trioxide entering the first microreactor+the sulfur trioxide entering the second microreactor): (the chlorosulfonic acid entering the first microreactor+the chlorosulfonic acid entering the second microreactor): Organic bases: low carbon chain fatty acids = 1: 1.01: 1.0: 0.02: 0.2.

As a further improvement of the method for the continuous synthesis of p-toluenesulfonyl chloride of the present invention:

The secondary reaction mixture discharged from the second microreactor is cooled to 0-5°C in the material cooling pipe, and then enters the constant temperature static collector, and water (water temperature≤5°C) is added to the constant temperature static collector, so that p-toluenesulfonate The crude acid chloride is precipitated in a crystalline state, and finally separated by filtration in a tubular filter; the filter cake is the crude p-toluenesulfonyl chloride.

The filtrate is solvent, dilute sulfuric acid and a small amount of residual dissolved matter (such as o-toluenesulfonyl chloride as a by-product, low carbon chain fatty acid as a sulfone inhibitor, organic base as a catalyst for chlorosulfonation reaction positioning, etc.).

As a further improvement of the method for the continuous synthesis of p-toluenesulfonyl chloride of the present invention:

The device for synthesizing p-toluenesulfonyl chloride comprises two microreactors connected in series, the first microreactor and the second microreactor, and the pipe diameters of the first microreactor and the second microreactor are both 100-1000 microns.

The liquid holding capacity (volume of containing liquid) of the first microreactor is about 5-20ml, and the channel length is about 5000-20000mm;

The liquid holding capacity of the second microreactor is about 10-40ml, and the channel length is about 10000-30000mm.

The invention has continuous production, can realize precise control of reaction temperature, reaction time, and reaction material ratio, and greatly improves production efficiency. Due to the addition of sulfone inhibitors, it effectively solves the problem of easily producing a large amount of sulfone substances in the sulfonation of sulfur trioxide And the problem of polysulfides, to avoid the generation of hydrogen chloride gas.

The present invention adopts the microreactor to carry out the reaction and has the following characteristics: the material flow in the channel is turbulent, the mass transfer efficiency is high, the specific surface area is large, the heat transfer capacity is strong, and the reaction conditions such as reaction temperature, reaction time, and material ratio can be accurately controlled. The continuous automation of the process can realize several times of amplification without amplification effect. Because the micro-reactor adopted in the present invention has the structural design of high-efficiency mass transfer and heat transfer, it can ensure that the chlorosulfonation reaction materials are fully mixed in a very short time and in a very small space, and reach the set temperature. The reaction occurs under certain conditions, which minimizes the occurrence of side reactions (inhibits the production of "sulfone substances" and "multi-sulfonated substances"), and will neither cause local overheating to aggravate side reactions, nor will it be flammable and explosive possibility. Under the reaction condition that the present invention sets, owing to the adding of sulfur trioxide, the hydrogen chloride gas that makes trace decomposition or trace and toluene reaction produces is absorbed by sulfur trioxide, becomes chlorosulfonic acid again, so the use of chlorosulfonic acid can be close to theory Quantity, high product yield, good quality, can greatly reduce the output of waste acid, easy to realize automatic production. These characteristics are unmatched by traditional pipeline reactors and tank reactors.

Explanation: Hydrogen chloride gas is produced when chlorosulfonic acid sulfonates toluene. Only when sulfur trioxide exists at the same time as hydrogen chloride gas is produced, can it be absorbed by sulfur trioxide. In the prior art, there is no process of using sulfur trioxide and chlorosulfonic acid at the same time. Usually, sulfur trioxide is used for sulfonation first, and then chlorosulfonic acid is used for acylchlorination after sulfonation is completed.

The present invention fully considered the following technical points during the invention process:

1. Sulfur trioxide and chlorosulfonic acid enter the microchannel reactor at the same time; its advantages are: because the reactivity of sulfur trioxide is higher than that of chlorosulfonic acid, chlorosulfonic acid can be used as a diluent for sulfur trioxide to reduce the concentration of sulfur trioxide. Reactivity, coupled with the addition of inhibitors of sulfone substances (lower fatty acids), can effectively prevent the production of sulfone substances and polysulfides. At the same time, sulfur trioxide can effectively absorb hydrogen chloride produced by micro-decomposition or micro-reaction of chlorosulfonic acid Gas, so that it turns into chlorosulfonic acid again, and hydrogen chloride gas will not be produced in the process:

SO ₃ +HCl→HSO ₃ Cl

2. In the first microreactor, the main chemical reaction is sulfonation reaction. In the sulfonation reaction involving sulfur trioxide, the generation of sulfone substances is the most important side reaction, and the inhibition of sulfone substances Generation is the core issue. Therefore, when entering the first microreactor, the molar amount of sulfur trioxide is far less than that of toluene, which is not enough to produce sulfone substances, effectively inhibiting the production of sulfone substances and polysulfonated substances;

At the outlet of the first microreactor, the reacted mixture enters the second static mixer, and after being mixed with sulfur trioxide, chlorosulfonic acid, and sulfone inhibitors, enters the second microreactor, and in the second microreactor First, sulfur trioxide continues to sulfonate toluene to generate p-toluenesulfonic acid, at this time, sulfone inhibitors play a role; at the same time, p-toluenesulfonic acid reacts with chlorosulfonic acid to generate p-toluenesulfonyl chloride (this reaction does not produce hydrogen chloride gas).

3. The present invention is continuous feeding;

Sulfur trioxide sulfonation is under specific reaction conditions, such as: under mass transfer, heat transfer, temperature of reaction, catalyzer most suitable condition, the consumption of sulfur trioxide can be close to theoretical amount, i.e. toluene: sulfur trioxide=1:1( mol ratio), and the present invention has created such most suitable reaction conditions in the microreactor.

It can be seen from the preferred embodiment that the molar ratio of toluene to sulfur trioxide is 1:1.01, and the extra 0.01 mole is actually used to absorb hydrogen chloride gas.

The present invention solves the technical problems that have plagued the industry for many years; compared with the prior art, the present invention has the following technical advantages:

1. With the mixture of sulfur trioxide and chlorosulfonic acid as the chlorosulfonating agent, in the presence of a catalyst, the continuous production of p-toluenesulfonyl chloride has been realized, and the reaction temperature, reaction time, and reaction material composition can be realized. With precise control of the ratio, the product yield is significantly improved (up to 95.38%, based on toluene), the product quality is stable, and the content of impurities is significantly reduced. This process has the characteristics of continuous production and automation.

2. A suitable nitrogen-containing organic compound is selected as the catalyst (preferably pyridine, tetraethylammonium chloride), and the positioning catalytic effect is good, which can completely replace the existing ammonium chloride or ammonium sulfate, and the usage amount is only the existing catalyst 0.5-1% of ammonium chloride or ammonium sulfate. Low-carbon chain fatty acid substances are selected as the inhibitors of sulfone substances, and the production of sulfone substances is effectively suppressed during the reaction process; the subsequent separation and purification process can be greatly simplified.

3. The addition of sulfur trioxide absorbs the trace hydrogen chloride gas produced by the micro-decomposition of chlorosulfonic acid, and no hydrogen chloride is produced in the whole production process, which eliminates the process and equipment for absorbing hydrogen chloride gas; greatly simplifies the subsequent separation and purification process and equipment.

4. The consumption of raw materials is greatly reduced, the production process is shortened, a large number of production equipment is reduced, and the production cost is further reduced.

5. Reduce environmental pollution and improve the operating environment.

Description of drawings

The specific implementation manners of the present invention will be described in further detail below in conjunction with the accompanying drawings.

Fig. 1 is a process flow diagram for the continuous preparation of p-toluenesulfonyl chloride in a microchannel reactor.

Fig. 2 is the channel plate installation schematic diagram of the microchannel reactor among Fig. 1;

Fig. 3 is the schematic diagram of side A of the microchannel reactor channel plate among Fig. 2;

Fig. 4 is the B face schematic diagram of the microchannel reactor channel plate among Fig. 2;

Fig. 5 is the outlet of the second microreactor among Fig. 1 to the cooling pipeline (material cooling pipeline) schematic diagram that connects constant temperature static collector;

Fig. 6 is a schematic diagram of the tubular filter in Fig. 1;

Fig. 7 is a schematic diagram of the static mixer in Fig. 1 .

Detailed ways

The present invention is further described below in conjunction with specific embodiment, but protection scope of the present invention is not limited thereto:

Device example, a device for synthesizing p-toluenesulfonyl chloride, as shown in Figures 1 to 7, including a first static mixer, a first microreactor, a second static mixer, a second microreactor, a constant temperature static collection device, tube filter;

The outlet of the first static mixer is provided with a constant flow pump one, and the outlet of the second static mixer is provided with a constant flow pump two; the outlet of the first microreactor is provided with a check valve one, and the outlet of the second microreactor is provided with a single valve Two-way valve; the function of one-way valve one is to ensure that the material can only flow from the first microreactor to the second static mixer, but not reverse flow. Similarly, the function of one-way valve two is to ensure that the material can only flow from the first microreactor The second microreactor flows to the material cooling pipeline;

Toluene, sulfur trioxide, chlorosulfonic acid, the solvent containing catalyzer (chlorosulfonation reaction positioning catalyst), the reservoirs of these 4 are respectively connected with the feed inlet of the first static mixer after respective metering pumps;

Sulfur trioxide, chlorosulfonic acid, and the solvent containing inhibitors, the reservoirs of these three are respectively connected to the feed inlet of the second static mixer after respective metering pumps;

The outlet of the first static mixer, constant flow pump one, the first microreactor, one-way valve one, and the inlet of the second static mixer are connected in sequence, and the outlet of the second static mixer, constant flow pump two, and the second microreactor The reactor, check valve 2, material cooling pipe, and the inlet of the constant temperature static collector are connected in sequence;

The inlet of the constant temperature static collector is located at the top of the constant temperature static collector (that is, the upper inlet), and the top of the constant temperature static collector is also equipped with a water inlet for adding dilution water. The bottom of the constant temperature static collector is set an exit (i.e., for a lower exit);

The outlet of the constant temperature static collector, the feeding pump, and the pipe filter are connected in sequence;

The constant temperature static collector is about 10 to 15 times the volume of the channel of the second microreactor.

The first microreactor and the second microreactor are conventional microreactors, specifically as follows: Fig. 3 and Fig. 4 are two faces of A and B of a microchannel plate in a microreactor, and the microchannel plate is made of carbonized Made of silicon material. When in use, face A of the microchannel plate to face A of another microchannel plate, and face B to face B of another microchannel plate. The material flows through the microchannel formed on the A-A surface to carry out a chemical reaction; the temperature control liquid flows in the channel formed on the B-B surface, thereby controlling the temperature of the material in the channel on the A-A surface. The temperature control liquid used in the present invention is: diethylene glycol dimethyl ether.

The total length of the reaction channel of the first microreactor (that is, the microchannel formed by the A-A face) is 10000～30000mm, and the pipe diameter is 100～1000 microns; the second microreactor reaction channel (that is, the microchannel formed by the A-A face ) has a total length of 20,000 to 40,000 mm and a pipe diameter of 100 to 1,000 microns.

The material cooling pipe is made of 316L stainless steel, and the length and pipe diameter can be set according to the cooling requirements, for example, the length is about 50cm and the pipe diameter is about 1mm.

When actually working:

1), after toluene, sulfur trioxide, chlorosulfonic acid, the solvent containing catalyst (sulfonation reaction positioning catalyst) are mixed in the first static mixer, utilize constant flow pump to inject first micro-reactor to carry out sulfonation reaction;

2), the reaction product (that is, first reaction mixture) that the first microreactor gained flows in the second static mixer, and relies on the respective metering pumps to be pumped into the sulfur trioxide, chlorosulfonic acid in the second static mixer 1. The solvent containing the inhibitor is mixed in the second static mixer; the resulting mixed material is injected into the second microreactor using a constant flow pump to continue the sulfonation and chlorosulfonation reactions;

3), the reaction product obtained in the second microreactor flows into the material cooling pipe for cooling, and the cooled reaction product (temperature is about 0-5° C.) enters the post-treatment process (including cooling, crystallization, and separation), as follows:

The cooled reaction product enters the constant temperature static collector, and water is added to the constant temperature static collector from the feed port of the constant temperature static collector (water temperature≤5°C); the crude p-toluenesulfonyl chloride is precipitated in a crystalline state, The solid-liquid mixture of discharge enters in the tubular filter and carries out filtration and separation; Filter cake is p-toluenesulfonyl chloride crude product, and filtrate is solvent, dilute sulfuric acid and a small amount of residual dissolved matter (as o-toluenesulfonyl chloride as by-product, as sulfones Low-carbon chain fatty acids as substance inhibitors, organic bases as catalysts for chlorosulfonation reactions, etc.).

The crude p-toluenesulfonyl chloride can be refined according to a conventional solvent method, and this refining method belongs to conventional technology, so it will not be described in detail in the present invention.

Explanation: In the second microreactor, chlorosulfonic acid and p-toluenesulfonic acid undergo a sulfonyl chloride reaction to generate sulfuric acid. After this sulfuric acid enters the constant temperature collector, when water is added, it becomes dilute sulfuric acid and remains in the reaction mixture.

The following embodiments: all adopt the above-mentioned device example. And: used chlorosulfonic acid is industrial chlorosulfonic acid, and purity is 98%; Calculate consumption by 100% during calculation.

Embodiment 1, a kind of method utilizing microreactor to continuously synthesize p-toluenesulfonyl chloride:

The feed table for entering the first static mixer is as described in Table 1, and the feed amount in Table 1 refers to the amount of raw materials entering the first static mixer. The feed table for entering the second static mixer is as described in Table 2; the amount of feed in Table 2 refers to the amount of raw materials entering the second static mixer.

Pyridine is selected as the sulfonation reaction positioning catalyst (catalyst for short), acetic acid (acetic acid) is selected as the sulfone substance inhibitor (inhibitor for short), and dichloromethane is selected as the organic solvent.

Table 1, the feed list that enters the first static mixer

name	molecular weight	moles	Feed amount (g)
toluene	92.14	1	92.14
sulphur trioxide	80.06	0.6	48.00
Chlorosulfonic acid (100%)	116.52	0.5	58.26
pyridine	79.10	0.02	1.58
Dichloromethane	the	the	135.4ml (about 180.10g)

Table 2, the feed list that enters the second static mixer

name	molecular weight	moles	Feed amount (g)
toluene	92.14	0	0
sulphur trioxide	80.06	0.41	32.8
Chlorosulfonic acid (100%)	116.52	0.50	58.26
acetic acid	46.05	0.2	9.21
Dichloromethane	the	the	99.6ml (132.50g)

details as follows:

1), 0.02mol of pyridine was dissolved in 135.4ml of dichloromethane as a solvent containing catalyst;

According to the molar ratio of toluene: sulfur trioxide: chlorosulfonic acid: pyridine = 1:0.6:0.5:0.02, toluene, sulfur trioxide, chlorosulfonic acid, and catalyst-containing solvents are sent into the first static state with respective metering pumps. The mixer is used for mixing, and the temperature in the first static mixer is not higher than -5°C (generally -10°C to -5°C);

The mixed material flowing out from the outlet of the first static mixer is injected into the first microreactor with 1.0ml/min by the constant flow pump to carry out the toluene sulfonation reaction. The retention volume of the first microreactor is about 20ml, so the mixed material is The residence time (reaction time) in a microreactor is about 20 minutes; Control the reaction temperature in the first microreactor to be 25 ℃; The outlet of the first microreactor discharges reaction mixture for the first time; This reaction mixture mainly consists of toluene for the first time , chlorosulfonic acid, p-toluenesulfonic acid and solvent, at this time, sulfur trioxide has been basically consumed;

2), the first reaction mixture discharged from the first microreactor enters the second static mixer after one-way valve; when the first reaction mixture appears in the second static mixer, start to inject Table 2 in the second static mixer Reaction starting materials listed.

Dissolve 0.2mol of acetic acid in 99.6ml of dichloromethane as a solvent containing inhibitors;

According to sulfur trioxide: chlorosulfonic acid: the mol ratio of acetic acid=0.41:0.5:0.2, sulfur trioxide, chlorosulfonic acid, the solvent containing inhibitor are sent into the second static mixer and the first static mixer with respective metering pumps respectively. The first reaction mixture flowing out of the microreactor is mixed; the temperature in the second static mixer is controlled not to be higher than 25°C (generally 10°C to 25°C);

The feed time of the reaction raw material in control table 1 is identical with the reaction raw material in table 2; That is, control toluene: (the sulfur trioxide that enters the first microreactor+the sulfur trioxide that enters the second microreactor): ( Chlorosulfonic acid entering the first microreactor + chlorosulfonic acid entering the second microreactor): pyridine as catalyst: acetic acid as inhibitor = 1: (0.6+0.41): (0.5+0.5): 0.02: 0.2=1:1.01:1:0.02:0.2.

The mixed material flowing out from the outlet of the second static mixer is injected into the second microreactor at 1.50ml/min by the constant flow pump two to continue the sulfonation and chlorosulfonation reactions, and the retention volume of the second microreactor is about 35ml Therefore, the residence time (reaction time) of the mixed material in the second microreactor is about 23 minutes; the temperature of reaction in the second microreactor is controlled to be 40°C;

The outlet of the second microreactor discharges the secondary reaction mixture; this secondary reaction mixture is mainly composed of solvent, p-toluenesulfonic acid as main product, sulfuric acid and o-toluenesulfonyl chloride as by-product, residual low carbon chain fatty acid (as Sulfone inhibitors), organic bases (as catalysts for sulfonation reactions).

4) After the secondary reaction mixture discharged from the outlet of the second microreactor passes through the material cooling pipe, the temperature is lowered to 0-5° C., and then enters the constant temperature static collector. Water is injected into the constant temperature static collector, and the time for water to be injected into the constant temperature static collector is equal to the time for the secondary reaction mixture to enter the constant temperature static collector. The added dilution water is about 400ml (water temperature≤5°C).

The reaction mixture after dilution, after testing, the total content of sulfuric acid is 99 grams, therefore, the present invention realizes that the production amount of waste acid is reduced to close to theoretical amount (theoretical amount is 98.12 grams).

The diluted reaction mixture is pumped into the tubular filter by the feeding pump located at the bottom of the constant temperature static collector for filtration. The filter cake is the crude product of p-toluenesulfonyl chloride. Analysis by capillary gas chromatography: the purity of p-toluenesulfonyl chloride is 98.86%. Yield: 95.38%.

The filtrate is solvent, dilute sulfuric acid and a small amount of residual dissolved matter (such as o-toluenesulfonyl chloride, low-carbon chain fatty acids as sulfone inhibitors, organic bases as sulfonation reaction positioning catalysts, etc.).

Embodiment 2-5

The catalyst in embodiment 1 is replaced by pyridine respectively: piperazine, tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride; In Example 1.

Embodiment 6, cancel the use of catalyst in embodiment 1, all the other are equal to embodiment 1.

The results obtained are as follows in Table 3:

table 3

Example	catalyst	The molar ratio of	Input amount (g)	Yield %	purity%
2	Piperazine	0.02	1.72	95.20	98.33
3	Tetramethylammonium chloride	0.02	2.19	94.69	98.45
4	Tetraethylammonium chloride	0.02	3.31	94.55	98.45
5	Tetrabutylammonium chloride	0.02	5.56	94.03	98.36
6	blank	the	the	85.15	92.66

Examples 7-10

The inhibitor in embodiment 1 is replaced by trifluoroacetic acid, propionic acid, isopropionic acid, chloroacetic acid respectively by acetic acid, and molar consumption remains unchanged, still is 0.2mol, and all the other are equal to embodiment 1.

Embodiment 11, cancel the use of the inhibitor in embodiment 1, the rest is equal to embodiment 1.

The results obtained are as follows in Table 4:

Table 4

Example	Inhibitor	The molar ratio of	Input amount (g)	Yield %	purity%
7	Trifluoroacetate	0.2	22.8	95.28	98.36
8	propionic acid	0.2	14.8	94.36	98.06
9	Isopropionic acid	0.2	14.8	93.69	98.00
10	Chloroacetic acid	0.2	18.9	93.66	98.00
11	blank	the	the	88.00	91.36

Examples 12-15

The mol ratio of the toluene in embodiment 1 and sulfur trioxide is changed into as following table 5 respectively by 1:1.01, and the consumption of toluene remains unchanged, enters the sulfur trioxide of the first static mixer, enters the second static mixing The amount of sulfur trioxide in the container is specifically described in the following table 5; all the other are equal to embodiment 1.

The results obtained are as follows in Table 5:

table 5

Examples 16-19

The mol ratio of the toluene in the embodiment 1 and the chlorosulfonic acid is respectively changed into as following table 6 by 1:1, the consumption of toluene remains unchanged, enters the chlorosulfonic acid of the first static mixer, enters the second static mixing The amount of chlorosulfonic acid in the container is specifically described in the following table 6; all the other are equal to embodiment 1.

The results obtained are as follows in Table 6:

Table 6

Note: In Examples 16 and 17, due to the generation of hydrogen chloride gas, voids are formed in the channel of the microreactor, which affects the normal turbulent flow state, and the yield and purity are significantly reduced.

Chlorosulfonic acid and toluene sulfonation reaction will produce hydrogen chloride gas. In the present invention, the designed first microreactor reaction condition is the optimal condition of sulfur trioxide and toluene sulfonation reaction, and sulfonation reaction takes place preferentially, and under this condition, the reaction amount of chlorosulfonic acid is extremely low; But , when the concentration ratio of chlorosulfonic acid increases greatly, the sulfonation reaction between chlorosulfonic acid and toluene will also intensify, and the hydrogen chloride gas produced will increase in a large amount. The sulfur trioxide in the system cannot absorb excess hydrogen chloride, and the hydrogen chloride gas will be in micro Voids are created in the reactor, which affects the reaction result.

Examples 20-23

Change the reaction temperature in the first microreactor, the temperature of the second static mixer, change the reaction temperature in the second microreactor, all the other are equal to embodiment 1.

The results obtained are as follows in Table 7:

Table 7

Examples 24-25

By changing the feeding speed of the first microreactor and the second microreactor, thereby changing the retention time of the material in the microreactor, all the other are equal to embodiment 1.

The results obtained are as follows in Table 8:

Table 8

Example 26. The solvent in Example 1 was changed from dichloromethane to chloroform or 1,2-dichloroethane, and the volume consumption remained unchanged, and the obtained results were basically the same as in Example 1.

Comparative example 1, with reference to the mode of sequential use of "sulfur trioxide, chlorosulfonic acid" in the prior art:

The sulfur trioxide of 1.01mol all enters the first microreactor and reacts, that is, the amount of sulfur trioxide entering the second microreactor is 0; and, the chlorosulfonic acid of 1mol all enters the second microreactor to carry out Reaction, that is, the amount of chlorosulfonic acid entering the first microreactor is 0; the residence time of the reaction material in the first microreactor and the second microreactor is substantially equal to embodiment 1. The rest are equal to Example 1.

The obtained results are: the yield of the product p-toluenesulfonyl chloride: 75.21%, and the purity is 81.00%. And there is also the defect that the reaction product is very chaotic and difficult to separate.

Comparative example 2: 1.00mol toluene, 1.01mol sulfur trioxide, 1mol chlorosulfonic acid, 235ml methylene chloride, 1.58g (0.02mol) pyridine, 9.2g (0.2) acetic acid are all fed into the first static mixer, The resulting mixture enters the first microreactor through the constant flow pump at a flow rate of 1ml/min, and the reaction mixture directly enters the second microreactor without passing through the second static mixer, so the reaction time in the first microreactor is About 20 minutes, the reaction time in the second microreactor is about 35 minutes. The rest are equal to Example 1.

The obtained results are: the yield of the product p-toluenesulfonyl chloride: 65.21%, and the purity: 71.00%. And there is also the defect that the reaction product is very chaotic and difficult to separate.

Finally, it should be noted that the above examples are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and many variations are possible. All deformations that can be directly derived or associated by those skilled in the art from the content disclosed in the present invention should be considered as the protection scope of the present invention.

Claims (8)

1. The method for continuously synthesizing p-toluenesulfonyl chloride, taking toluene as reaction raw material, is characterized in that:

   1), after toluene, sulfur trioxide, chlorosulfonic acid, organic bases and solvent are mixed in the first static mixer, are pumped into the first microreactor under the effect of constant flow pump one and react;

   The reaction temperature in the first microreactor is 10-60°C, and the reaction time is 10-35 minutes;

   2), the first reaction mixture discharged from the outlet of the first microreactor flows into the second static mixer, and is pumped into sulfur trioxide, chlorosulfonic acid, low-carbon chain fatty acid and solvent in the second static mixer respectively Mixing is carried out in the second static mixer, and the resulting mixed material is pumped into the second microreactor for reaction under the action of the constant flow pump two;

   The reaction temperature of the second microreactor is 20～60 ℃, and the reaction time is 10～40 minutes;

   Toluene: (the sulfur trioxide entering the first microreactor+the sulfur trioxide entering the second microreactor): (the chlorosulfonic acid entering the first microreactor+the chlorosulfonic acid entering the second microreactor): Organic bases: low carbon chain fatty acids = molar ratio of 1:0.8～1.5:0.8～1.5:0.018～0.022:0.18～0.22;

   Enter the sulfur trioxide of the first microreactor: the mol ratio of the sulfur trioxide=(1.5 ± 0.1) that enters the second microreactor: 1;

   Enter the chlorosulfonic acid of the first microreactor: the mol ratio of the chlorosulfonic acid=1 that enters the second microreactor: (1 ± 0.1);

   3), the secondary reaction mixture discharged from the second microreactor is cooled, crystallized and separated to obtain p-toluenesulfonyl chloride as the product.
2. The method for continuously synthesizing p-toluenesulfonyl chloride according to claim 1, is characterized in that:

   The organic bases are any of the following: piperazine, tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride, melamine, pyridine, dodecylanilinotrimethylammonium chloride ;

   The low carbon chain fatty acid is any of the following: acetic acid, propionic acid, isopropionic acid, chloroacetic acid, trifluoroacetic acid.
3. The method for continuously synthesizing p-toluenesulfonyl chloride according to claim 2, is characterized in that:

   The sum of the solvent entering the first microreactor and the solvent entering the second microreactor is defined as the total solvent, and 200-300ml of total solvent is used for every 1mol of toluene;

   The solvent is any of the following: dichloromethane, chloroform, 1,2-dichloroethane.
4. The method for continuously synthesizing p-toluenesulfonyl chloride according to claim 3, is characterized in that:

   The temperature in the first static mixer is ≤ -5°C;

   The temperature in the second static mixer is ≤ 25°C.
5. The method for continuously synthesizing p-toluenesulfonyl chloride according to any one of claims 1 to 4, characterized in that:

   The reaction temperature in the first microreactor is 20～40 ℃, and the reaction time is 20～33 minutes;

   The reaction temperature in the second microreactor is 40～60 ℃, and the reaction time is 23～39 minutes;

   Toluene: (the sulfur trioxide entering the first microreactor+the sulfur trioxide entering the second microreactor): (the chlorosulfonic acid entering the first microreactor+the chlorosulfonic acid entering the second microreactor): Organic bases: low carbon chain fatty acids = molar ratio of 1:1-1.2:0.9-1.0:0.018-0.022:0.18-0.22.
6. The method for continuously synthesizing p-toluenesulfonyl chloride according to claim 5, is characterized in that:

   The reaction temperature in the first microreactor is 25 DEG C, and the reaction time is 20 minutes;

   The reaction temperature in the second microreactor is 40 DEG C, and the reaction time is 23 minutes;

   Toluene: (the sulfur trioxide entering the first microreactor+the sulfur trioxide entering the second microreactor): (the chlorosulfonic acid entering the first microreactor+the chlorosulfonic acid entering the second microreactor): Organic bases: low carbon chain fatty acids = 1: 1.01: 1.0: 0.02: 0.2.
7. The method for continuously synthesizing p-toluenesulfonyl chloride according to any one of claims 1 to 6, characterized in that:

   The secondary reaction mixture discharged from the second microreactor is cooled to 0-5°C in the material cooling pipe, and then enters the constant temperature static collector, and water is added to the constant temperature static collector, so that the crude p-toluenesulfonyl chloride is crystalline. Precipitate, and finally filter and separate in a tubular filter; the filter cake is crude p-toluenesulfonyl chloride.
8. The method for continuously synthesizing p-toluenesulfonyl chloride according to any one of claims 1 to 7, characterized in that:

   The device for synthesizing p-toluenesulfonyl chloride comprises two microreactors connected in series, the first microreactor and the second microreactor, and the pipe diameters of the first microreactor and the second microreactor are both 100-1000 microns.

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