CN117820198A - Treatment method of waste liquid from enamine synthesis reaction in BA progesterone synthesis process - Google Patents

Abstract

The invention provides a method for treating enamine synthesis waste liquid in a BA progesterone synthesis process. The method uses the recovered enamine synthesis waste liquid as a raw material, adds toluene, piperidine and p-toluenesulfonic acid, and realizes the reuse of piperidine cyclohexene and cyclohexanone through a series of reactions such as reflux. The method has a simple process, low cost and no secondary pollution.

Description

Treatment method of waste liquid from enamine synthesis reaction in BA progesterone synthesis process

Technical Field

The invention relates to the technical field of industrial waste liquid treatment, and in particular to a method for recovering acetonitrile and cyclohexanone from enamine synthesis waste liquid in a BA progesterone synthesis process.

Background technique

Acetonitrile is an organic compound, a colorless liquid, very volatile, with a special odor similar to ether, excellent solvent properties, and can dissolve a variety of organic, inorganic and gaseous substances. It has a certain degree of toxicity and is infinitely miscible with water and alcohol. Acetonitrile can undergo typical nitrile reactions and is used to prepare many typical nitrogen-containing compounds. It is an important organic intermediate. Acetonitrile can be used as a solvent for the synthesis of vitamin A, cortisone, carbon amine drugs and their intermediates, and is also used to make active medium solvents for vitamin B1 and amino acids. It can replace chlorinated solvents. It is used in vinyl coatings, and is also used as an extractant for fatty acids, an alcohol denaturant, a butadiene extractant, and a solvent for acrylonitrile synthetic fibers. It also has many uses in fabric dyeing, lighting, perfume manufacturing, and photosensitive material manufacturing.

Cyclohexanone is an organic compound, a saturated cyclic ketone with the carbonyl carbon atom included in the six-membered ring. It is a colorless, transparent liquid with an earthy smell. When it contains trace amounts of phenol, it has a minty smell. The impurities are light yellow, and the color changes with the storage time, and the impurities are formed, and the color is water white to grayish yellow, with a strong pungent odor. The explosive rate when mixed with air is the same as that of open-chain saturated ketones. In industry, it is mainly used as a raw material and solvent for organic synthesis. For example, it can dissolve nitrocellulose, coatings, paints, etc.

Piperidine cyclohexene is an important raw material for the enamine synthesis reaction in the BA synthesis of progesterone process. In the enamine synthesis reaction of the BA synthesis of progesterone process, piperidine cyclohexene and BA oxide are used as raw materials, and the reaction equation is as follows:

Piperidine cyclohexene is an important enamine reagent. The reaction will produce a certain amount of cyclohexanone, and the final waste liquid will contain cyclohexanone, solvent acetonitrile, excessive piperidine cyclohexene and enamine. These waste liquids, if not treated or improperly treated, will cause serious environmental pollution, and therefore must be treated. And if piperidine cyclohexene and enamine are not recovered, the waste of raw materials will also be caused, and the production cost will be greatly increased. Therefore, we are in urgent need of a simple and economical piperidine cyclohexene recovery technology. Although the specific process of the enamine synthesis reaction is introduced in the current patent CN112110971A, the treatment method of the waste liquid of this step reaction is not mentioned, and there is no report on the piperidine cyclohexene recovery technology in this waste liquid.

Summary of the invention

In view of the above problems, the present invention provides a method for treating the waste liquid of enamine synthesis in the process of BA synthesis of progesterone. The method uses the recovered waste liquid of enamine synthesis as a raw material, adds toluene, piperidine, and p-toluenesulfonic acid, and realizes the reuse of piperidine cyclohexene and cyclohexanone through a series of reactions such as reflux. The process is simple, the cost is low, and no secondary pollution is generated. The reaction equation is as follows:

This application is implemented through the following technical solutions:

A method for treating waste liquid from enamine synthesis reaction in a BA progesterone synthesis process, the method comprising the following steps performed in sequence:

Step 1, recovering the waste liquid from the enamine synthesis reaction in the BA synthesis process of progesterone;

Step 2, removing acetonitrile from the waste liquid to obtain a concentrated dry product;

Step 3, adding toluene to the concentrated dry product, and reflux to remove water until there is no water;

Step 4, adding piperidine and p-toluenesulfonic acid, and reflux to remove water until there is no water;

Step 5, removing toluene to obtain piperidine cyclohexene.

Preferably, step 2 uses distillation to remove acetonitrile from the waste liquid, and the distillation is atmospheric distillation or reduced pressure distillation; the atmospheric distillation temperature is 80-120° C., and the reduced pressure is operated according to the vacuum degree of the specific system, and the temperature does not exceed 120° C.;

Preferably, the weight ratio of the concentrated dry matter to toluene in step 3 is 1:3-8; the reflux temperature is 80-150° C.;

Preferably, the amount of piperidine added in step 4 is 0.5 to 1.5 times (molar ratio) of the cyclohexanone content in the waste liquid in step 1; the amount of p-toluenesulfonic acid added is 0.5% to 5% of piperidine; the reflux temperature is 80 to 150°C

Preferably, step 5 uses distillation to remove toluene, and the distillation is atmospheric distillation or reduced pressure distillation; the atmospheric distillation temperature is 80-150°C, and the reduced pressure distillation is operated according to the vacuum degree of the specific system, and the temperature does not exceed 150°C.

Preferably, the method comprises the following steps:

Step 1, adding waste liquid from enamine synthesis reaction in BA progesterone synthesis process into a reaction container;

Step 2, distilling under reduced pressure at about 50-80°C until there is no fraction, recovering acetonitrile to obtain a concentrated dry product;

Step 3, cooling to room temperature, adding 2-4 times the weight of toluene to the concentrated dry matter, heating to 100-110° C., reflux and remove water until there is no water;

Step 4, cooling to room temperature, adding piperidine with a cyclohexanone content of 1-1.2 times and p-toluenesulfonic acid with a piperidine weight of 1.5%-2%, heating to 100-110° C., reflux and remove water until there is no water;

Step 5, distill until there is no fraction, recover toluene, and obtain a concentrate, namely piperidine cyclohexene

The treatment method of the present application is reasonably designed, the process is simple, the toxicity to the working environment is low, the utilization rate of cyclohexanone is high, the recovery rate of piperidine cyclohexene is high, and the content of the obtained piperidine cyclohexene is 75-90% after gas phase detection. At the same time, it is verified by the synthesis reaction of enamine in the BA synthesis of progesterone process, and the quality meets the requirements.

The present application is by recycling cyclohexanone and unreacted piperidine cyclohexene, compared with the market tonnage purchase price (300 yuan/kg) of piperidine cyclohexene, cost reduction is about 190 yuan/kg, according to an annual output of 500 tons of progesterone, piperidine cyclohexene consumption is about 590 tons, and the piperidine cyclohexene consumption can be saved by this method. About 220 tons, 41.8 million yuan can be saved annually, greatly reducing the cost of raw material piperidine cyclohexene, thereby saving the cost of raw materials and auxiliary materials of BA synthesis progesterone process. In addition, the recovery and treatment process reclaims acetonitrile, piperidine cyclohexene and cyclohexanone which are polluted to the environment, and is basically pollution-free to the surrounding environment, saving environmental pollution control costs. According to an annual output of 500 tons of progesterone, about 200 tons of waste liquid are produced each year, and the cost of treating waste liquid is 5000 yuan/ton, which can save 1 million yuan annually.

Detailed ways

The following is a further detailed description of the present invention in combination with specific preferred embodiments, which does not mean that the specific embodiments of the present invention are only examples. For those skilled in the art of the present invention, simple substitutions that are easy to make without departing from the concept of the present invention should be considered as falling within the scope of protection of the present invention.

The raw materials (i.e., the waste liquid from the enamine synthesis reaction) used in the following examples refer to the synthesis step S2 of compound 3 in patent CN112110971A, and the filtrate after cooling, crystallization and filtration is the waste liquid from the enamine synthesis reaction.

Example 1

Step 1, 600 g of waste liquid from the enamine synthesis reaction in the BA progesterone synthesis process (containing about 6.5% cyclohexanone after measurement) was added to a 1000 ml reaction bottle;

Step 2, distilling under reduced pressure at about 60°C until there is no fraction, recovering about 550g of acetonitrile, and leaving about 100g of concentrated dry matter;

Step 3, cooling to room temperature, adding 400 ml of toluene to the concentrated dry product, heating to 110° C., reflux and remove water until there is no water;

Step 4, cool to room temperature, add 32 g of piperidine and 0.6 g of p-toluenesulfonic acid, heat to 110° C., reflux and remove water until there is no water;

Step 5, distilling until there is no fraction, recovering about 380 ml of toluene, and obtaining about 75 g of concentrate with a piperidine cyclohexene content of 83%.

Example 2

Step 1, 600g of waste liquid from enamine synthesis reaction in BA progesterone synthesis process (containing about 6% cyclohexanone after measurement) was added into a 1000ml reaction bottle;

Step 2, distilling under reduced pressure at about 60°C until there is no fraction, recovering about 550g of acetonitrile, and leaving about 100g of concentrated dry matter;

Step 3, cooling to room temperature, adding 400 ml of toluene to the concentrated dry product, heating to 110° C., reflux and remove water until there is no water;

Step 4, cool to room temperature, add 29 g piperidine and 0.6 g p-toluenesulfonic acid, heat to 110° C., reflux and remove water until there is no water;

Step 5, distilling until there is no fraction, recovering about 380 ml of toluene, and obtaining about 70 g of concentrate with a piperidine cyclohexene content of 78%.

Example 3

Step 1, 600 g of waste liquid from enamine synthesis reaction in BA progesterone synthesis process (containing about 7% cyclohexanone after measurement) was added into a 1000 ml reaction bottle;

Step 2, distilling under reduced pressure at about 60°C until there is no fraction, recovering about 550g of acetonitrile, and leaving about 100g of concentrated dry matter;

Step 3, cooling to room temperature, adding 400 ml of toluene to the concentrated dry product, heating to 110° C., reflux and remove water until there is no water;

Step 4, cool to room temperature, add 34 g piperidine and 0.7 g p-toluenesulfonic acid, heat to 110° C., reflux and remove water until there is no water;

Step 5, distill until there is no fraction, recover about 380 ml of toluene, and obtain about 76 g of concentrate with a piperidine cyclohexene content of 87%.

Claims (10)

1. A method for treating enamine synthesis reaction waste liquid in a BA progesterone synthesis process is characterized by comprising the following steps of:

step 1, recovering waste liquid of enamine synthesis reaction in a BA (methyl acetate) progesterone synthesis process;

step 2, acetonitrile in the waste liquid is removed, and a concentrated dry matter is obtained;

step 3, adding toluene into the concentrated dry matter, and refluxing and water diversion until no water exists;

step 4, adding piperidine and p-toluenesulfonic acid, and refluxing and water diversion until no water exists;

and 5, removing toluene to obtain the piperidine cyclohexene.

2. The method of claim 1, wherein step 2 is performed by distillation to remove acetonitrile from the effluent.

3. The method of claim 2, wherein the distillation is atmospheric distillation or reduced pressure distillation; the atmospheric distillation temperature is 80-120 ℃, and the reduced pressure distillation temperature is not more than 120 ℃.

4. The process of claim 1, wherein the weight ratio of concentrated dry matter to toluene in step 3 is 1:3-8.

5. The method of claim 1, wherein the reflux temperature in step 3 is 80 to 150 ℃.

6. The method of claim 1, wherein the piperidine is added in the step 4 in an amount of 0.5 to 1.5 times the cyclohexanone content in the waste liquid obtained in the step 1; the addition amount of the p-toluenesulfonic acid is 0.5-5% of piperidine.

7. The method of claim 1, wherein the reflux temperature of step 4 is 80 to 150 ℃.

8. The process of claim 1 wherein step 5 employs distillation to remove toluene.

9. The method of claim 9, wherein the distillation is atmospheric distillation or reduced pressure distillation; the atmospheric distillation temperature is 80-150 ℃, and the reduced pressure distillation temperature is not more than 150 ℃.

10. A method for treating enamine synthesis reaction waste liquid in a process of synthesizing progesterone by BA is characterized by comprising the following steps:

step 1, adding waste liquid of enamine synthesis reaction in a BA (methyl acetate) progesterone synthesis process into a reaction vessel;

step 2, distilling under reduced pressure of about 50-80 ℃ until no fraction exists, and recovering acetonitrile to obtain a concentrated dry matter;

step 3, cooling to room temperature, adding toluene with the weight 2-4 times of that of the concentrated dry matter into the concentrated dry matter, heating to 100-110 ℃, and refluxing and water diversion until no water exists;

step 4, cooling to room temperature, adding piperidine with the cyclohexanone content of 1-1.2 times and p-toluenesulfonic acid with the piperidine weight of 1.5% -2%, heating to 100-110 ℃ and refluxing for water diversion until no water exists;

step 5, distilling until no fraction exists, and recovering toluene to obtain a concentrate, namely piperidine cyclohexene.