CN108047054B - A kind of method for separating and purifying o-iodoaniline by melt crystallization - Google Patents

Abstract

The invention discloses a method for separating and purifying o-iodoaniline by melt crystallization, which comprises the following steps: 1) grinding the raw materials of the mixture of o-iodoaniline and p-iodoaniline into powder to obtain product A; 2) putting product A into a crystallizer , then open the crystallizer, heat the product A, make the product A completely melt, and obtain the product B; 3) cool the product B to crystallize it, after reaching the final crystallization temperature, carry out crystal growth, and then release the mother liquor to obtain the product C; 4 ) Gradually heat up the product C and sweat until the final temperature of sweating, release sweat, and the remaining crystals are purified o-iodoaniline. The method of the invention has the characteristics of no need to use an organic solvent, environmental protection, high separation and purification efficiency, small loss of o-iodoaniline, low cost, and high purity of the obtained o-iodoaniline, and is suitable for industrialization.

Description

A kind of method for separating and purifying o-iodoaniline by melt crystallization

technical field

The invention relates to a method for separating and purifying o-iodoaniline, in particular to a method for separating and purifying o-iodoaniline by melting crystallization.

Background technique

O-iodoaniline and its derivatives can be used as raw materials for the preparation of indole anticancer drugs. With appropriate catalysts, various indole drug intermediates can be efficiently synthesized. With its wide application in the fields of medicine, pesticides and materials, The demand for o-iodoaniline will continue to rise. Indole compounds are a class of heterocyclic derivative alkaloids with significant physiological activities. In the development of new drugs, indole structures are often prioritized as lead compounds. O-iodoaniline can be reacted with alkynes to prepare indole by Larock-Castro synthesis method, or indole derivatives can be obtained by Heck method under palladium catalysis. O-iodoaniline and its derivatives are often used for the preparation of indole anticancer drugs, and have high market value. Further synthesis can obtain high-end synthetic intermediates with complex structures, which have more prominent market prospects and price advantages. In the synthesis of o-iodoaniline, the obtained product is generally a mixture of o-iodoaniline and p-iodoaniline, which must be separated and purified to obtain purer o-iodoaniline. Direct substitution and synthesis of o-iodoaniline is accompanied by the generation of isomer p-iodoaniline. In the preparation method of patent 201610944091.3 a kind of o-iodoaniline, it is mentioned that methods such as extraction crystallization, recrystallization and column chromatography separation are used to purify, but the efficiency low, the yield is only 45%. However, the high temperature environment of o-iodoaniline is easy to deteriorate, so it is not suitable for separation and purification by rectification.

As an interdisciplinary separation and production technology, industrial crystallization technology has become an indispensable and important technology in bioengineering, material science and other industries, and has become one of the basic means of high-tech development in the 21st century. As a kind of industrial crystallization technology, melt crystallization technology was developed in the last century. It has attracted much attention because it does not need to use solvents and has the advantages of green environmental protection. Patent 201610283094.7 mentions a method for separating and purifying 2,5-dichlorophenol by melt crystallization, namely separating 2,5-dichlorophenol from the isomer mixture of 2,5-dichlorophenol and 2,4-dichlorophenol Chlorophenol, under the premise of ensuring a good separation rate, the purity of the separated 2,5-dichlorophenol can reach more than 97%. In patent 201410442674.7, a method for separating milk fat based on melt layer crystallization technology, the anhydrous milk fat is melted under stirring at an elevated temperature, and the temperature is lowered to grow a crystal layer on the outer surface of the inner jacket; the mother liquor is discharged, and after the temperature is raised Decompression to remove sweat; collect crystals to obtain high melting point milk fat, and products with a narrow melting point range can be obtained according to different actual needs.

The melt crystallization method has the advantages of low energy consumption, no solvent and high product purity, and is of great significance in the separation and purification of organic matter. In view of the above problems, a simple and efficient melt crystallization process is considered for the separation and purification of isomer components to reduce production costs. At present, there is no relevant report on the literature and invention patent of purifying o-(p-)iodoaniline using melt crystallization technology.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a method for separation and purification of o-iodoaniline by melt crystallization. The method of the invention has the characteristics of no need to use an organic solvent, environmental protection, high separation and purification efficiency, small loss of o-iodoaniline, low cost, and high purity of the obtained o-iodoaniline, and is suitable for industrialization.

Technical scheme of the present invention:

A method for separating and purifying o-iodoaniline by melt crystallization, comprising the following steps:

1) Grind the raw materials of the mixture of o-iodoaniline and p-iodoaniline into powder to obtain product A;

2) Put product A into the crystallizer, then open the crystallizer, heat product A, make product A completely melt, and obtain product B;

3) Cool the temperature of product B to make it crystallize, grow the crystal after reaching the final temperature of crystallization, and then release the mother liquor to obtain product C;

4) Gradually increase the temperature of product C and sweat until the final temperature of sweating, release sweat, and the remaining crystals are purified o-iodoaniline.

In the aforementioned method for separating and purifying o-iodoaniline by melt crystallization, in the described A product, o-iodoaniline accounts for more than 55% of the total mass fraction.

The aforementioned method for separating and purifying o-iodoaniline by melt crystallization, the A product is put into a crystallizer and heated to 25-75° C. for melting.

In the aforementioned method for separating and purifying o-iodoaniline by melt crystallization, when the temperature of the product B is lowered, the cooling rate is 0.5-5°C/h.

In the aforementioned method for separating and purifying o-iodoaniline by melt crystallization, the final temperature of the crystallization is 10-50°C.

In the aforementioned method for separating and purifying o-iodoaniline by melt crystallization, the crystal growing time is 0.5-10 hours.

In the aforementioned method for separating and purifying o-iodoaniline by melt crystallization, when the product C sweats, the heating rate is 0.5-5°C/h, and the final temperature of sweating is 15-60°C.

The beneficial effects of the present invention

1. The separation and purification method of the present invention can separate o-iodoaniline from the isomer mixture of o-iodoaniline and p-iodoaniline, and has few losses, low cost, easy operation, high purity, and can meet the needs of industrialized production. Proved by practice, when the yield of the o-iodoaniline of the present invention reaches more than 60%, the purity of the o-iodoaniline reaches more than 99%.

2. The raw material of the present invention only needs to be heated to 25-75° C. to be melted, and this temperature range can ensure that the mixture of o-iodoaniline and p-iodoaniline is in a molten state, which is conducive to subsequent impurity removal and improvement of product purity.

3. The cooling crystallization of the present invention reduces the temperature of the system to 10-50 °C at a cooling rate of 0.5-5 °C/h, and then grows the crystal for 0.5-10 hours. This condition can ensure that most of the o-iodoaniline and a small amount of p-iodine are Aniline isomers can be solidified into crystals, which are convenient for sweat purification operations.

4. In the present invention, the temperature is gradually increased to sweat, and the temperature is increased at a rate of 0.5-5 °C/h until the final temperature of sweating is 15-50 °C. This condition can prevent the heating rate from being too fast or too slow to affect the effect of removing impurities from sweating. Only in this condition The range can ensure that the sweating operation achieves the best impurity removal effect and removes a small amount of p-iodoaniline in the o-iodoaniline.

Example:

5g of the isomer mixture of o-iodoaniline and p-iodoaniline (the mass fraction of o-iodoaniline is 70.95%) is ground into powder and added to the jacketed crystallizer, and the temperature is raised to 55°C to melt the raw materials; h cooling rate to cool down the molten liquid until the final crystallization temperature is 28°C; part of the crystals are precipitated, and after growing for 2 hours, the mother liquor is released; the crystal part is heated and sweated at a heating rate of 1.2°C/h until the final temperature of sweating is 40°C °C to remove sweat. The temperature is then raised to melt the product out of the crystallizer, the collected product. Weighing calculation, the yield is 61.75%. Detected by gas chromatography, the purity of the product is 99.07%, and the melting point of the product measured by a micro melting point apparatus is 52 ℃-53.5 ℃, which is consistent with the literature value. The gas chromatogram and infrared spectrum of the product are shown in Figure 1 and Figure 2.

It can be seen from the gas chromatogram of Figure 1 that there is mainly one peak in the obtained product, and the retention time is 7.256min. According to the retention time of the standard sample, the substance that appeared at 7.256min was o-iodoaniline. Gas chromatographic detection showed that the mass fraction of o-iodoaniline was 99.07% (Agilent 4890D gas chromatograph SE-54).

In the infrared spectrum of Figure 2, compared with the standard sample of o-iodoaniline, there are N-H absorption peaks at 3200-3400cm-1, benzene ring absorption peaks at 1400-1600cm-1, and C-I absorption peaks at 510cm-1 Peak and C-N absorption peak at 1250cm-1, para C-H absorption peak at 830cm-1. The main component was determined by infrared to be o-iodoaniline.

Description of drawings

Accompanying drawing 1 is the gas chromatogram of o-iodoaniline standard sample and product;

Accompanying drawing 2 is the gas chromatogram of o-iodoaniline standard sample and product.

Detailed ways

The present invention will be further described below in conjunction with the examples, but not as a basis for limiting the present invention.

Embodiments of the present invention

Embodiment 1: a method for separation and purification of o-iodoaniline by melt crystallization, comprising the following steps:

1) Select 55% o-iodoaniline and p-iodoaniline mixture that o-iodoaniline accounts for the total mass fraction as raw materials, and grind it into powder to obtain product A;

2) Put product A into the crystallizer, then open the crystallizer, and heat product A to 75°C, so that product A is completely melted, and product B is obtained;

3) Cooling the product B at a rate of 5°C/h to make it crystallize, after reaching the final crystallization temperature of 50°C, the crystal is grown for 0.5 hours, and then the mother liquor is released to obtain the product C;

4) Gradually increase the temperature of product C at a rate of 5°C/h and sweat, until the final temperature of sweating is 60°C, sweat is released, and the remaining crystals are purified o-iodoaniline.

Embodiment 2: a method for separation and purification of o-iodoaniline by melt crystallization, comprising the following steps:

1) Select 65% o-iodoaniline and p-iodoaniline mixture that o-iodoaniline accounts for the total mass fraction as raw materials, and grind it into powder to obtain product A;

2) Put product A into the crystallizer, then open the crystallizer, and heat product A to 65°C, so that product A is completely melted, and product B is obtained;

3) Cooling the product B at a rate of 4.1°C/h to make it crystallize, after reaching the final crystallization temperature of 42°C, the crystal is grown for 2 hours, and then the mother liquor is released to obtain the product C;

4) Gradually increase the temperature of product C at a rate of 4.1°C/h and sweat, until the final temperature of sweating is 50°C, sweat is released, and the remaining crystals are purified o-iodoaniline.

Embodiment 3: a method for separation and purification of o-iodoaniline by melt crystallization, comprising the following steps:

1) Select 75% o-iodoaniline and p-iodoaniline mixture that o-iodoaniline accounts for the total mass fraction as raw materials, and grind it into powder to obtain product A;

2) Put product A into the crystallizer, then open the crystallizer, and heat product A to 55°C, so that product A is completely melted, and product B is obtained;

3) Cooling the product B at a rate of 3°C/h to make it crystallize, reaching the final crystallization temperature of 33°C and growing the crystal for 5 hours, and then releasing the mother liquor to obtain the product C;

4) Gradually increase the temperature of product C at a rate of 3°C/h and sweat, until the final temperature of sweating is 40°C, sweat is released, and the remaining crystals are purified o-iodoaniline.

Embodiment 4: a method for separation and purification of o-iodoaniline by melt crystallization, comprising the following steps:

1) Select o-iodoaniline and p-iodoaniline mixture that o-iodoaniline accounts for 85% of the total mass fraction as raw materials, and grind it into powder to obtain product A;

2) Put product A into the crystallizer, then open the crystallizer, and heat product A to 45°C, so that product A is completely melted, and product B is obtained;

3) Cooling the product B at a rate of 1.5°C/h to crystallize it, after reaching the final crystallization temperature of 20°C, the crystal is grown for 8 hours, and then the mother liquor is released to obtain the product C;

4) Gradually increase the temperature of product C at a rate of 1.5°C/h to sweat, until the final temperature of sweating is 25°C, sweat is released, and the remaining crystals are purified o-iodoaniline.

Embodiment 5: a method for separation and purification of o-iodoaniline by melt crystallization, comprising the following steps:

1) Select the o-iodoaniline and p-iodoaniline mixture that o-iodoaniline accounts for 90% of the total mass fraction as raw materials, and grind it into powder to obtain product A;

2) Put product A into the crystallizer, then open the crystallizer, heat product A to 25°C, make product A completely melt, and obtain product B;

3) Cooling product B at a rate of 0.5°C/h to make it crystallize, after reaching the final crystallization temperature of 10°C, grow the crystal for 10 hours, and then release the mother liquor to obtain product C;

4) Gradually increase the temperature of product C at a rate of 0.5°C/h and sweat, until the final temperature of sweating is 15°C, sweat is released, and the remaining crystals are purified o-iodoaniline.

Claims (2)

1. A method for separating and purifying o-iodoaniline by melt crystallization is characterized by comprising the following steps: the method comprises the following steps:

1) grinding the mixture of o-iodoaniline and p-iodoaniline into powder to obtain product A;

2) putting the product A into a crystallizer, then opening the crystallizer, heating the product A to 55 ℃, and completely melting the product A to obtain a product B;

3) cooling the product B to crystallize at a cooling rate of 3.6 ℃/h until the final crystallization temperature reaches 28 ℃, then growing the crystal for 2 hours, and then discharging the mother liquor to obtain a product C;

4) and (3) gradually heating the product C to sweat at the heating rate of 1.2 ℃/h until the final temperature of the sweating is 40 ℃, discharging sweat, and obtaining the residual crystal which is the purified o-iodoaniline.

2. The method for separating and purifying o-iodoaniline by melt crystallization according to claim 1, wherein the method comprises the following steps: in the A product, o-iodoaniline accounts for more than 55% of the total mass.

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