CN115974783A - Preparation method of 5-amino-3-cyano-1- (2, 6-dichloro-4-trifluoromethylphenyl) pyrazole - Google Patents

Abstract

The invention discloses a method for preparing 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole by p-trifluoromethylaniline, comprising: p-trifluoromethylaniline Methylaniline reacts with dilute hydrochloric acid and hydrogen peroxide, and chlorination produces 2,6-dichloro-4-trifluoromethylaniline; 2,6-dichloro-4-trifluoromethylaniline is then reacted with nitrosyl chloride under acidic The diazotization reaction generates diazonium chloride salt; the diazonium chloride salt is condensed with ethyl 2,3-dicyanopropionate under acidic conditions, and after hydrolysis, the hydrolyzed organic phase is catalyzed by ammonia water or ammonia gas Cyclization generates 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole; hydrolyzed aqueous phase is adsorbed by weak base anion exchange resin to obtain dilute hydrochloric acid solution , can be used as a chlorination reagent for recycling and chlorination reactions. The method not only avoids the treatment of a large amount of waste salt, but also can recycle the by-products of diazotization, which greatly saves the consumption of chlorination reagents.

Description

A kind of preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole

technical field

The invention belongs to the technical field of chemical engineering, and specifically relates to a preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

Background technique

5-Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole is referred to as pyrazole ring, and its molecular formula is C ₁₁ H ₅ Cl ₂ F ₃ N ₄ . An important intermediate of the insecticides fipronil and ethiprole. The pure product is a white crystalline solid, and the industrial product is a light yellow-brown solid with a melting point of 141-142°C. It is soluble in methanol, ethanol, acetone, dichloroethane and ethyl acetate.

Chinese patents CN103396366A, CN110240566A etc. disclose a kind of preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, with 2,6-di Chloro-4-trifluoromethylaniline is used as a raw material, sulfuric acid is used as a reaction medium, and an aqueous solution of sodium nitrite is added dropwise to obtain a diazonium salt solution of 2,6-dichloro-4-trifluoromethylaniline through a diazotization reaction , then add ethyl 2,3-dicyanopropionate for reaction, and then generate 5-amino-3-cyano-1-(2,6-dichloro-4 -trifluoromethylphenyl)pyrazole. The patented reaction produces a large amount of waste acid, the "three wastes" are difficult to deal with, and the yield is low.

Chinese patent CN106220565A discloses a preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, with 2,6-dichloro-4 -Trifluoromethylaniline is a raw material, with nitrosyl sulfuric acid as a diazotization reagent, then adding 2,3-dicyanopropionic acid ethyl ester to react, and then cyclization in an organic solvent under weakly alkaline conditions to generate 5 -Amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole. Although this method avoids the use of sodium nitrite, it still needs to deal with a large amount of sulfuric acid by-products.

There is following shortcoming in above-mentioned prior art;

1. Prior art In the process of synthesizing 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, the diazotization process mostly uses sodium nitrite and Concentrated sulfuric acid is used to prepare nitrous acid. Because sodium nitrite introduces sodium ions, the reaction solution is a mixed solution containing a large amount of sodium sulfate, sulfuric acid and acetic acid. This part of the waste water still needs a large amount of liquid caustic soda to neutralize the excess acid. Salt is mixed and finally desalted by evaporation. This process is not only difficult to handle, but also causes a lot of waste of raw materials and energy.

2. Prior art In the process of synthesizing 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, part of the diazotization process uses nitrosyl sulfuric acid Sodium nitrite is replaced to avoid the formation of sodium salt, but nitrosyl sulfuric acid will generate sulfuric acid to form a mixed acid system of sulfuric acid and acetic acid, which is not only difficult to handle, but also sulfuric acid cannot be applied mechanically in this process.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole. It has the following advantages: First, the diazotization process uses nitrosyl chloride instead of sodium nitrite to avoid the production of sodium salts, and fundamentally reduces the difficulty of wastewater treatment; second, the raw materials and products of the chlorination section and the diazotization section are combined Organically combined, the hydrochloric acid produced in the diazo chemical section is effectively separated and returned to the chlorination section as raw material, which not only reduces the treatment of waste acid, but also saves the cost of raw materials.

The present invention is achieved through the following technical solutions:

A preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, comprising the following steps:

Step 1, chlorination: p-trifluoromethylaniline, dilute hydrochloric acid and hydrogen peroxide, chlorination reaction occurs at a temperature of 40-50°C to obtain 2,6-dichloro-4-trifluoromethylaniline, p-trifluoromethyl The molar ratio of aniline, dilute hydrochloric acid and hydrogen peroxide is 1:(3～4):(2.0～2.1); the chlorination reaction solution is allowed to stand for stratification, and the organic phase of the chlorination reaction of the lower layer is taken to enter step 2 for diazotization;

Step 2, diazotization: add acetic acid and nitrosyl chloride to the organic phase of the chlorination reaction obtained in step 1, and react at a temperature of 10-20°C to obtain 2,6-dichloro-4-trifluoromethyl The molar ratio of benzene chloride diazonium salt, 2,6-dichloro-4-trifluoromethylaniline and nitrosyl chloride is 1: (1-1.05); the diazotization reaction product enters step 3;

Step 3, condensation: Add ethyl 2,3-dicyanopropionate and acetic acid to the diazotization reaction product, and undergo a condensation reaction at a temperature of 20-35°C to obtain 2,3-dicyano-2 -(2,6-dichloro-trifluoromethylphenylazo) ethyl propionate; 2,6-dichloro-4-trifluoromethylbenzene diazonium chloride, 2,3-dicyano The molar ratio of ethyl propionate is 1: (1～1.1); the condensation reaction product enters step 4;

Step 4, hydrolysis: add water to the condensation reaction product, carry out hydrolysis, leave the hydrolyzate standing, layering, the water phase of the hydrolyzate enters step 6, and the organic phase of the hydrolyzate enters step 5; the condensation reaction product The mass ratio to the added water is 1:0.5～0.7;

The aqueous phase of the hydrolyzate is an acidic aqueous phase containing hydrochloric acid and acetic acid;

The organic phase of the hydrolyzate is an organic phase containing cyanoazo compounds;

Step 5, cyclization: add ammonia water or ammonia gas to the organic phase of the hydrolyzate, and a cyclization reaction occurs at a temperature of 20-40° C. to obtain a cyclization reaction product, and the cyclization reaction product enters step 7;

Step 6, adsorption: adding a weakly basic ion exchange resin to the water phase of the hydrolyzate, absorbing acetic acid in the water phase of the hydrolyzate, and recycling the water phase of the hydrolyzate after the adsorption is completed to step 1;

The temperature of the saturated weakly basic ion exchange resin is raised to 120-130°C, and the acetic acid adsorbed on the weakly basic ion exchange resin is desorbed, and the desorbed acetic acid is recovered by condensation and returned to step 2 and/or step 3 ;

Due to the polarity difference between acetic acid and hydrochloric acid, acetic acid is adsorbed in the resin and the water phase after adsorption is dilute hydrochloric acid solution, which can be recycled back to step 1, chlorination;

Step 7, refining: add toluene to the cyclization reaction product, conduct cooling crystallization, the cooling rate is 1-4°C/h, the cooling end point temperature is 0-10°C, and the crystalline solid is dried to obtain 5-amino-3- The refined product of cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

Toluene can be used as a solvent to dissolve the crude product, and then the cooling crystallization process can further purify the product, and the obtained crystallized product will be evaporated during the drying process and will not remain in the final product.

In the above technical solution, in the step 1, the concentration of the hydrochloric acid solution is 15-16 wt%, and the concentration of the hydrogen peroxide is 27.0-28.0 wt%.

In the above technical solution, in the step 4, the time for the hydrolysis reaction is 1-2 hours, and the reaction temperature is room temperature.

In the step 5 described in the above technical solution, the concentration of ammonia water is 20-25wt%.

In the above technical scheme, in the step 6, the saturated weakly basic ion exchange resin is warmed up to 120-130 degrees Celsius, and the acetic acid adsorbed on the weakly basic ion exchange resin is desorbed, and the desorbed acetic acid passes through Condensation recovery, return to step 2 and/or step 3.

In the above technical solution, the ion exchange resin in step 6 is a weak base ion exchange resin, preferably A-654 macroporous weak base anion exchange resin, HPA-330 epoxy weak base anion exchange resin.

In the above technical scheme, the acetic acid added in the step 2 and step 3 is mainly used as a solvent and does not participate in the reaction.

Advantage of the present invention and beneficial effect are:

1. 2,6-dichloro-p-trifluoromethylaniline and nitrosyl chloride are diazotized under the action of dilute hydrochloric acid. As the active substance, nitrosyl chloride not only has a fast reaction speed, but also the product is HCl and can be dissolved in In dilute hydrochloric acid, there is no introduction of other impurity ions in the reaction, especially the formation of sodium salt without the introduction of sodium ions.

2. The waste water from the diazotization condensation reaction is reused. After the condensation reaction, a large amount of acidic wastewater of dilute hydrochloric acid and organic acid is produced. The acidic wastewater is treated by the method of ion exchange absorption and extraction, and the obtained dilute hydrochloric acid can be returned to the process as a reactant of the chlorination reaction.

Through the method disclosed in the present invention, compared with the traditional production method, the present invention avoids the treatment of a large amount of waste acid and waste salt, and the hydrochloric acid generated in the diazotization reaction can be recycled as a chlorination reagent in the chlorination reaction; While greatly reducing waste water treatment, it also reduces raw material consumption.

Detailed ways

In order to enable those skilled in the art to better understand the solution of the present invention, the technical solution of the present invention will be further described below in conjunction with specific examples.

Example 1

A preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, comprising the following steps:

Step 1, chlorination: add p-trifluoromethylaniline 20.0g, 15.5wt% dilute hydrochloric acid 87.6g, 27.5wt% hydrogen peroxide 30.7g to the chlorination kettle, react at 40-43°C for 2h; Set the layers, remove the organic phase of the chlorination reaction in the lower layer and enter step 2 for diazotization; the organic phase is 2,6-dichloro-p-trifluoromethylaniline, weighing 28.6g;

Step 2, diazotization: add 23.9 g of acetic acid to the organic phase of the chlorination reaction obtained in step 1, pass in 8.1 g of nitrosyl chloride gas, and react at 10-15 ° C for 5 h to obtain 2,6-dichloro -4-trifluoromethylbenzene diazonium chloride; the diazotization reaction product enters step 3;

Step 3, condensation: Add 19.0 g of ethyl 2,3-dicyanopropionate and 17.4 g of acetic acid to the diazotization reaction product, and react at 20-25°C for 3 hours to obtain 97.0 g of condensation product, condensation product Mainly ethyl 2,3-dicyano-2-(2,6-dichloro-trifluoromethylphenylazo)propionate; the condensation reaction product enters step 4;

Step 4, hydrolysis: add 25g of water to the condensation reaction product, hydrolyze at 20-25°C for 1 hour, and then stand and separate layers to obtain 70.8g of the aqueous phase layer and 51.2g of the organic phase layer, and the aqueous phase of the hydrolyzed product enters Step 6, the organic phase of the hydrolyzate enters step 5;

The aqueous phase of the hydrolyzate is an acidic aqueous phase containing hydrochloric acid and acetic acid;

The organic phase of the hydrolyzate is an organic phase containing cyanoazo compounds;

Step 5, cyclization: inject 3 g of ammonia gas into the organic phase of the hydrolyzate, react at 20-25° C. for 1 h, and obtain 54.2 g of cyclization product; proceed to step 7 for refining;

Step 6, adsorption: place in the water phase of the hydrolyzate in an adsorption column equipped with A-654 macroporous weak base anion exchange resin, adsorb for 1 hour at normal temperature, and absorb the acetic acid in the water phase of the hydrolyzate , the liquid after adsorption is 29.2g of 15.5wt% hydrochloric acid; the hydrochloric acid can be recycled to the chlorination step;

The saturated weakly basic ion exchange resin is heated to 125-130 degrees, and the acetic acid adsorbed on the weakly basic ion exchange resin is desorbed, and the desorbed acetic acid is recovered by condensation, and returns to step 2 and/or step 3 ;

Step 7, refining: add 100.0 g of toluene to the cyclization product of step 5, let stand to separate layers, discard the water layer, and cool the organic layer to 5°C at a cooling rate of 2-3°C/h, filter, and filter the cake After drying, 37.6 g of the refined product of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole was obtained.

Example 2:

A preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, comprising the following steps:

Step 1, chlorination: add p-trifluoromethylaniline 20.2g in the chlorination kettle, dilute hydrochloric acid 29.2g that embodiment 1 step 6 obtains, fresh 15.4wt% hydrochloric acid 58.4g, 27.3wt% hydrogen peroxide 31.9g, in 43 Reaction at -46°C for 2 hours; the chlorination reaction solution was left to stand and separated, and the organic phase of the chlorination reaction in the lower layer was taken into step 2 for diazotization; the organic phase was 2,6-dichloro-p-trifluoromethylaniline and weighed to obtain 28.9g ;

Step 2, diazotization: add 24 g of acetic acid to the organic phase of the chlorination reaction obtained in step 1, pass in 8.2 g of nitrosyl chloride gas, and react at 12-15 ° C for 5 h to obtain 2,6-dichloro- 4-trifluoromethylbenzene diazonium chloride; diazotization reaction product enters step 3;

Step 3, condensation: Add 19.1 g of ethyl 2,3-dicyanopropionate and 17.5 g of acetic acid to the diazotization reaction product, and react at 25-28°C for 3 hours to obtain 97.7 g of the condensation product. The product is mainly 2,3-dicyano-2-(2,6-dichloro-trifluoromethylphenylazo) ethyl propionate; the condensation reaction product enters step 4;

Step 4, hydrolysis: add 25.2 g of water to the condensation reaction product, hydrolyze at 22-25 ° C for 1 h, and then stand and separate layers to obtain 71.0 g of the aqueous phase layer, 51.9 g of the organic phase layer, and the aqueous phase of the hydrolyzed product Enter step 6, the organic phase of hydrolyzate enters step 5;

The aqueous phase of the hydrolyzate is an acidic aqueous phase containing hydrochloric acid and acetic acid;

The organic phase of the hydrolyzate is an organic phase containing cyanoazo compounds;

Step 5, cyclization: add 15.1 g of 20 wt % ammonia water to the organic phase of the hydrolyzate, react at 20-25° C. for 1 hour, and obtain 67.0 g of cyclization product; go to step 7 for refining;

Step 6, adsorption: place in the water phase of the hydrolyzate in an adsorption column equipped with HPA-330 epoxy series weakly basic anion exchange resin, adsorb for 1 hour at normal temperature, and absorb the water in the water phase of the hydrolyzate Acetic acid, the liquid after adsorption is 29.8g of 15.4wt% hydrochloric acid; hydrochloric acid can be recycled to the chlorination step;

The saturated weakly basic ion exchange resin is heated to 125-130 degrees, and the acetic acid adsorbed on the weakly basic ion exchange resin is desorbed, and the desorbed acetic acid is recovered by condensation, and returns to step 2 and/or step 3 ;

Step 7, refining: add 101.0 g of toluene to the cyclization product of step 5, let stand to separate the layers, discard the water layer, and cool the organic layer to 5°C at a cooling rate of 2-3°C/h, filter, and filter the cake After drying, 37.3 g of the refined product of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole was obtained.

Example 3:

A preparation method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole, comprising the following steps:

Step 1, chlorination: add p-trifluoromethylaniline 20.1g in the chlorination kettle, dilute hydrochloric acid 29.8g that embodiment 2 step 6 obtains, fresh 15.4wt% hydrochloric acid 58.2g, 27.5wt% hydrogen peroxide 31.0g, at 40 Reaction at -43°C for 2 hours; the chlorination reaction solution was left to stand and separated, and the organic phase of the chlorination reaction in the lower layer was taken into step 2 for diazotization; the organic phase was 2,6-dichloro-p-trifluoromethylaniline and weighed to obtain 28.7g ;

Step 2, diazotization: add 23.6 g of acetic acid to the organic phase of the chlorination reaction obtained in step 1, feed 8.1 g of nitrosyl chloride gas, and react at 12-15 °C for 5 hours to obtain 2,6-dichloro -4-trifluoromethylbenzene diazonium chloride; the diazotization reaction product enters step 3;

Step 3, condensation: Add 19.0 g of ethyl 2,3-dicyanopropionate and 17.5 g of acetic acid to the diazotization reaction product, and react at 25-28°C for 3 hours to obtain 96.9 g of the condensation product. The product is mainly 2,3-dicyano-2-(2,6-dichloro-trifluoromethylphenylazo) ethyl propionate; the condensation reaction product enters step 4;

Step 4, hydrolysis: add 25.1 g of water to the condensation reaction product, hydrolyze at 21-25 ° C for 1 h, and then stand and separate layers to obtain 70.2 g of the aqueous phase layer, 51.8 g of the organic phase layer, and the aqueous phase of the hydrolyzed product Enter step 6, the organic phase of hydrolyzate enters step 5;

The aqueous phase of the hydrolyzate is an acidic aqueous phase containing hydrochloric acid and acetic acid;

The organic phase of the hydrolyzate is an organic phase containing cyanoazo compounds;

Step 5, cyclization: add 13.5g of 25wt% ammonia water to the organic phase of the hydrolyzate, react at 20-25°C for 1 hour, and obtain 65.3g of cyclization product; go to step 7 for refining;

Step 6, adsorption: place in the water phase of the hydrolyzate in an adsorption column equipped with A-654 macroporous weak base anion exchange resin, adsorb for 1 hour at normal temperature, and absorb the acetic acid in the water phase of the hydrolyzate , the liquid after adsorption is 29.4g of 15.5wt% hydrochloric acid; hydrochloric acid can be recycled to the chlorination step;

The temperature of the weakly basic ion exchange resin after adsorption saturation is raised to 122-125 degrees Celsius, and the acetic acid adsorbed on the weakly basic ion exchange resin is desorbed, and the desorbed acetic acid is recovered by condensation, and returns to step 2 and/or step 3 ;

Step 7, refining: Add 100.5 g of toluene to the cyclization product of step 5, let stand to separate layers, discard the water layer, and cool the organic layer to 5°C at a cooling rate of 2-3°C/h, filter, and filter the cake After drying, 36.6 g of the refined product of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole was obtained.

The present invention has been described as an example above, and it should be noted that, without departing from the core of the present invention, any simple deformation, modification or other equivalent replacements that can be made by those skilled in the art without creative labor all fall within the scope of this invention. protection scope of the invention.

Claims (7)

1. a 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method, is characterized in that, comprises the following steps: Step 1, chlorination: p-trifluoromethylaniline, dilute hydrochloric acid and hydrogen peroxide, chlorination reaction occurs at a temperature of 40-50°C to obtain 2,6-dichloro-4-trifluoromethylaniline, p-trifluoromethyl The molar ratio of aniline, dilute hydrochloric acid and hydrogen peroxide is 1:(3～4):(2.0～2.1); the chlorination reaction solution is allowed to stand for stratification, and the organic phase of the chlorination reaction of the lower layer is taken to enter step 2 for diazotization; Step 2, diazotization: add acetic acid and nitrosyl chloride to the organic phase of the chlorination reaction obtained in step 1, and react at a temperature of 10-20°C to obtain 2,6-dichloro-4-trifluoromethyl The molar ratio of benzene chloride diazonium salt, 2,6-dichloro-4-trifluoromethylaniline and nitrosyl chloride is 1: (1-1.05); the diazotization reaction product enters step 3; Step 3, condensation: Add ethyl 2,3-dicyanopropionate and acetic acid to the diazotization reaction product, and undergo a condensation reaction at a temperature of 20-35°C to obtain 2,3-dicyano-2 -(2,6-dichloro-trifluoromethylphenylazo) ethyl propionate; 2,6-dichloro-4-trifluoromethylbenzene diazonium chloride, 2,3-dicyano The molar ratio of ethyl propionate is 1: (1～1.1); the condensation reaction product enters step 4; Step 4, hydrolysis: add water to the condensation reaction product, carry out hydrolysis, leave the hydrolyzate standing, layering, the water phase of the hydrolyzate enters step 6, and the organic phase of the hydrolyzate enters step 5; the condensation reaction product The mass ratio to the added water is 1:0.5～0.7; Step 5, cyclization: add ammonia water or ammonia gas to the organic phase of the hydrolyzate, and a cyclization reaction occurs at a temperature of 20-40° C. to obtain a cyclization reaction product, and the cyclization reaction product enters step 7; Step 6, adsorption: adding a weakly basic ion exchange resin to the water phase of the hydrolyzate, absorbing acetic acid in the water phase of the hydrolyzate, and recycling the water phase of the hydrolyzate after the adsorption is completed to step 1; Step 7, refining: add toluene to the cyclization reaction product, conduct cooling crystallization, the cooling rate is 1-4°C/h, the cooling end point temperature is 0-10°C, and the crystalline solid is dried to obtain 5-amino-3- The refined product of cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole. 2. 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method according to claim 1, is characterized in that, described step 1 In the method, the concentration of the hydrochloric acid solution is 15-16 wt%, and the concentration of the hydrogen peroxide is 27.0-28.0 wt%. 3. 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method according to claim 1, is characterized in that, described step 4 In the method, the time of the hydrolysis reaction is 1 to 2 hours, and the reaction temperature is room temperature. 4. 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method according to claim 1, is characterized in that, described step 5 Among them, the concentration of ammonia water is 20-25wt%. 5. 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method according to claim 1, is characterized in that, described step 6 In the process, the temperature of the saturated weakly basic ion exchange resin is raised to 120-130°C, and the acetic acid adsorbed on the weakly basic ion exchange resin is desorbed, and the desorbed acetic acid is recovered by condensation, and returns to step 2 and/or Step 3. 6. 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method according to claim 1, is characterized in that, described step 6 The ion exchange resin in is a weak base ion exchange resin, preferably A-654 macroporous weak base anion exchange resin, HPA-330 epoxy series weak base anion exchange resin. 7. 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) pyrazole preparation method according to claim 1, is characterized in that, described step 2 And the acetic acid added in step 3 is mainly used as a solvent and does not participate in the reaction.