CN110668928A - Synthesis method of high-purity 4-chloro-4' -hydroxybenzophenone - Google Patents
Synthesis method of high-purity 4-chloro-4' -hydroxybenzophenone Download PDFInfo
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- RUETVLNXAGWCDS-UHFFFAOYSA-N (4-chlorophenyl)-(4-hydroxyphenyl)methanone Chemical compound C1=CC(O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 RUETVLNXAGWCDS-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000001308 synthesis method Methods 0.000 title description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims abstract description 52
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- 238000001816 cooling Methods 0.000 claims abstract description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 30
- 238000010438 heat treatment Methods 0.000 claims abstract description 27
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 22
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 21
- 238000005406 washing Methods 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 17
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 12
- 239000000243 solution Substances 0.000 claims abstract description 12
- 239000000047 product Substances 0.000 claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 9
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 claims abstract description 7
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000011259 mixed solution Substances 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 230000007062 hydrolysis Effects 0.000 claims description 12
- 238000006460 hydrolysis reaction Methods 0.000 claims description 12
- 238000000746 purification Methods 0.000 claims description 11
- 238000000605 extraction Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000004537 pulping Methods 0.000 claims description 9
- 238000004042 decolorization Methods 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 239000012295 chemical reaction liquid Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- 238000004321 preservation Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims 1
- 238000010009 beating Methods 0.000 claims 1
- 238000005119 centrifugation Methods 0.000 claims 1
- 230000035484 reaction time Effects 0.000 abstract description 11
- 239000006227 byproduct Substances 0.000 abstract description 5
- 230000001276 controlling effect Effects 0.000 abstract 2
- 239000012043 crude product Substances 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000003814 drug Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000011085 pressure filtration Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000005457 optimization Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 2
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 2
- 229960002297 fenofibrate Drugs 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- UGVRJVHOJNYEHR-UHFFFAOYSA-N 4-chlorobenzophenone Chemical compound C1=CC(Cl)=CC=C1C(=O)C1=CC=CC=C1 UGVRJVHOJNYEHR-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing high-purity 4-chloro-4' -hydroxybenzophenone, which comprises the steps of cooling chlorobenzene and anisole to below 5 ℃; adding anhydrous aluminum trichloride in three batches, controlling the temperature, dropwise adding a mixed solution of p-chlorobenzoyl chloride and chlorobenzene, and controlling the reaction temperature; after the addition, maintaining the low temperature, heating to the normal temperature, and then maintaining the normal temperature for reaction; adding anhydrous aluminum trichloride at one time, and then heating to react in two stages; cooling and hydrolyzing; and (4) centrifugally washing to obtain a crude product, washing by using sodium carbonate and sodium hydroxide solution, regulating the pH value by using hydrochloric acid, and centrifugally separating to obtain a fine product. The invention has fine temperature control, can reduce by-products by combining the control of reaction time, and has the purity of more than 99.9 percent.
Description
Technical Field
The invention relates to a synthetic method of a drug intermediate, in particular to a synthetic method of high-purity 4-chloro-4' -hydroxybenzophenone.
Background
The purity of the drug, i.e., the reduction and control of by-products, has a great influence on the therapeutic effects and side effects of the drug. The difference of the purity of the product as a pharmaceutical intermediate, which is a few tenths of a percent, affects the sale and price of the product.
4-chloro-4' -hydroxybenzophenone, 4-CBP for short, is an important intermediate of fenofibrate drugs, and after the effect is found, the research on the synthesis of the fenofibrate drugs is not stopped. Although a plurality of catalysts and synthesis routes appear after years of development, the classical traditional synthesis route still has a place in production, and the root cause is that the aluminum trichloride is cheap and has better cost control. However, it should be formally understood that the conventional synthesis route and the use of aluminum trichloride have many byproducts and low overall purity, and the fundamental reasons are that the temperature is not precisely controlled, the reaction time and the temperature are not matched, that is, the effective reaction time is not well controlled, and the reaction conditions are rough, and the invention carries out detailed optimization work in order to further optimize the conventional synthesis route.
In addition, for the improvement and optimization of the purification process, fine adjustment is also needed to be performed in a matching manner, so that the purity of the whole synthesis process is improved to a greater extent.
Disclosure of Invention
In order to improve the synthesis method, reduce by-products and improve purity, the invention provides an optimized synthesis method of high-purity 4-chloro-4' -hydroxybenzophenone, wherein the purity is over 99.9 percent, and the technical scheme is as follows:
a method for synthesizing high-purity 4-chloro-4' -hydroxybenzophenone is characterized by comprising the following steps: the following parts are all parts by weight;
(1) putting 735 parts of chlorobenzene and 150 parts of anisole into a reaction kettle, and cooling to below 5 ℃;
(2) adding total 120 ~ 200 parts of anhydrous aluminum trichloride in three batches, controlling the temperature to be below 5 ℃, and stirring for 2 ~ 4 hours;
(3) dropwise adding a mixed solution of 245 parts of p-chlorobenzoyl chloride and 120 parts of chlorobenzene, controlling the reaction temperature to be 0 ~ 5 ℃, and finishing the addition within 10 hours;
(4) after the addition, the temperature is maintained at 0 ~ 5 ℃, and the reaction is carried out for 1 ~ 3 hours;
(5) heating to normal temperature, and maintaining the normal temperature for reaction for 1 ~ 3 hours;
(6) adding 150 parts of anhydrous aluminum trichloride at one time, and stirring for 0.5 ~ 2 hours;
(7) heating to 80 ℃, and reacting for 0.5 ~ 1 hours at constant temperature;
(8) then heating to 125 ~ 130 ℃ and reacting for 2 ~ 4 hours at constant temperature;
(9) cooling to below 40 ℃ to prepare for hydrolysis;
(10) adding 2000 parts of water into a hydrolysis kettle, cooling to below 30 ℃, and dropwise adding the reaction liquid, wherein the reaction temperature is not higher than 40 ℃;
(11) after the addition, the reaction is carried out for 0.5 ~ 2 hours under the condition of heat preservation;
(12) cooling to below 10 ℃, centrifuging and washing with water to obtain the 4-chloro-4' -hydroxybenzophenone.
Further comprises a purification step of dispersing, pulping and washing the prepared 4-chloro-4' -hydroxybenzophenone by 1000 parts by weight of a 2% sodium carbonate solution, and then centrifuging and separating.
Preferably, the purification step further comprises the steps of pulping, washing and centrifuging the sodium carbonate solution, dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of a 2% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, continuously adding 5 parts by weight of activated carbon into the water phase, heating for decolorization, press-filtering, adjusting the pH value of the filtrate to be less than 2 by using concentrated hydrochloric acid at 60 ~ 70 ℃, cooling to below 20 ℃ for precipitation, and centrifuging to separate out a fine product with the purity of more than 99%.
Preferably, in the purification step, chlorobenzene is mechanically used for 5 times after extraction and layering, and then is repeatedly used after rectification.
Further, in the purification step, the hydrochloric acid tail gas is treated by water absorption.
Further, the anhydrous aluminum trichloride in the step (2) accounts for 160 parts by weight in total, and is added and evenly distributed for three times.
Further, the normal temperature in the step (2) is 25 ℃.
Further optimization in reaction time was performed as: the reaction time in the step (2) is 3 hours; the reaction time in the step (4) is 2 hours; the reaction time in the step (5) is 3 hours; the reaction time in the step (6) is 1 hour, the reaction time in the step (7) is 0.5 hour, the reaction time in the step (8) is 3 hours, and the reaction time in the step (11) is 1 hour.
Advantageous effects
1. According to the technical scheme, the temperature control is more accurate, the connection conversion of the optimal synthesis temperature of each step is further optimized, byproducts can be reduced, and the purity is improved.
2. The technical scheme of the invention has good purification process effect, and can ensure that the purity of the final product exceeds 99 percent.
The specific implementation mode is as follows:
in order to better express the technical scheme of the invention, the invention is explained by combining the embodiment.
Example 1
The synthesis process comprises the following steps: (1) putting 735 parts of chlorobenzene and 150 parts of anisole into a reaction kettle, and cooling to below 5 ℃;
(2) adding 120 parts of anhydrous aluminum trichloride in three batches, controlling the temperature to be below 5 ℃, and stirring for 2 hours;
(3) dropwise adding a mixed solution of 245 parts of p-chlorobenzoyl chloride and 120 parts of chlorobenzene, controlling the reaction temperature to be 0 ~ 5 ℃, and finishing the addition within 10 hours;
(4) after the addition, the temperature is maintained at 0 ~ 5 ℃, and the reaction is carried out for 1 hour;
(5) heating to normal temperature, and maintaining the temperature at 25 ℃ for reaction for 1 hour;
(6) adding 150 parts of anhydrous aluminum trichloride at one time, and stirring for 0.5 hour;
(7) heating to 80 ℃, and reacting for 0.5 hour at constant temperature;
(8) then heating to 125 ~ 130 ℃ and reacting for 2 hours at constant temperature;
(9) cooling to below 40 ℃ to prepare for hydrolysis;
(10) adding 2000 parts of water into a hydrolysis kettle, cooling to below 30 ℃, and dropwise adding the reaction liquid, wherein the reaction temperature is not higher than 40 ℃;
(11) after the addition, the reaction is carried out for 0.5 hour under the condition of heat preservation;
(12) cooling to below 10 ℃, and centrifugally washing to obtain the 4-chloro-4' -hydroxybenzophenone;
(13) dispersing, pulping and washing the prepared 4-chloro-4' -hydroxybenzophenone by 1000 parts by weight of 2% sodium carbonate solution, and then performing centrifugal separation;
(14) dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of a 2% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, continuously adding 5 parts by weight of activated carbon into a water phase, heating for decolorization, performing pressure filtration, adjusting the pH value of filtrate to be less than 2 by using concentrated hydrochloric acid at 60 ~ 70 ℃, cooling to below 20 ℃ for precipitation, and performing centrifugal separation to obtain a refined product with the purity of over 99.91%.
Example 2
The synthesis process comprises the following steps: (1) putting 735 parts of chlorobenzene and 150 parts of anisole into a reaction kettle, and cooling to below 5 ℃;
(2) adding 200 parts of anhydrous aluminum trichloride in three batches, controlling the temperature to be below 5 ℃, and stirring for 4 hours;
(3) dropwise adding a mixed solution of 245 parts of p-chlorobenzoyl chloride and 120 parts of chlorobenzene, controlling the reaction temperature to be 0 ~ 5 ℃, and finishing the addition within 10 hours;
(4) after the addition, the temperature is maintained at 0 ~ 5 ℃, and the reaction is carried out for 3 hours;
(5) heating to normal temperature, and maintaining the normal temperature for reaction for 3 hours;
(6) adding 150 parts of anhydrous aluminum trichloride at one time, and stirring for 2 hours;
(7) heating to 80 ℃, and reacting for 1 hour at constant temperature;
(8) then heating to 125 ~ 130 ℃ and reacting for 4 hours at constant temperature;
(9) cooling to below 40 ℃ to prepare for hydrolysis;
(10) adding 2000 parts of water into a hydrolysis kettle, cooling to below 30 ℃, and dropwise adding the reaction liquid, wherein the reaction temperature is not higher than 40 ℃;
(11) after the addition, the reaction is carried out for 2 hours under the condition of heat preservation;
(12) cooling to below 10 ℃, and centrifugally washing to obtain the 4-chloro-4' -hydroxybenzophenone;
(13) dispersing, pulping and washing the prepared 4-chloro-4' -hydroxybenzophenone by 1000 parts by weight of 2% sodium carbonate solution, and then performing centrifugal separation;
(14) dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of a 2% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, continuously adding 5 parts by weight of activated carbon into a water phase, heating for decolorization, performing pressure filtration, adjusting the pH value of filtrate to be less than 2 by using concentrated hydrochloric acid at 60 ~ 70 ℃, cooling to below 20 ℃ for precipitation, and performing centrifugal separation to obtain a refined product with the purity of over 99.92%.
Example 3
The synthesis process comprises the following steps: (1) putting 735 parts of chlorobenzene and 150 parts of anisole into a reaction kettle, and cooling to below 5 ℃;
(2) adding 160 parts of anhydrous aluminum trichloride in three batches, uniformly distributing each batch, controlling the temperature to be below 5 ℃, and stirring for 3 hours;
(3) dropwise adding a mixed solution of 245 parts of p-chlorobenzoyl chloride and 120 parts of chlorobenzene, controlling the reaction temperature to be 0 ~ 5 ℃, and finishing the addition within 10 hours;
(4) after the addition, the temperature is maintained at 0 ~ 5 ℃, and the reaction is carried out for 2 hours;
(5) heating to normal temperature, and maintaining the normal temperature for reaction for 3 hours;
(6) adding 150 parts of anhydrous aluminum trichloride at one time, and stirring for 1 hour;
(7) heating to 80 ℃, and reacting for 0.5 hour at constant temperature;
(8) then heating to 125 ~ 130 ℃ and reacting for 3 hours at constant temperature;
(9) cooling to below 40 ℃ to prepare for hydrolysis;
(10) adding 2000 parts of water into a hydrolysis kettle, cooling to below 30 ℃, and dropwise adding the reaction liquid, wherein the reaction temperature is not higher than 40 ℃;
(11) after the addition, the reaction is carried out for 1 hour under the condition of heat preservation;
(12) cooling to below 10 ℃, centrifuging and washing with water to obtain the 4-chloro-4' -hydroxybenzophenone.
(13) Dispersing, pulping and washing the prepared 4-chloro-4' -hydroxybenzophenone by 1000 parts by weight of 2% sodium carbonate solution, and then performing centrifugal separation;
(14) dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of a 2% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, continuously adding 5 parts by weight of activated carbon into a water phase, heating for decolorization, performing pressure filtration, adjusting the pH value of filtrate to be less than 2 by using concentrated hydrochloric acid at 60 ~ 70 ℃, cooling to below 20 ℃ for precipitation, performing centrifugal separation to obtain a fine product, and controlling the temperature and the time to be combined with each other to ensure that the purity is over 99.95%.
Example 4
The synthesis process comprises the following steps: the difference from the embodiment 3 is that,
other steps are not changed, if the step (2) is changed into: a total of 170 parts of anhydrous aluminum trichloride was charged in three portions, and the mixture was stirred at a temperature of 5 ℃ or lower for 3 hours. The purity was 98%.
Other steps are not changed, if the step (2) is changed into: a total of 110 parts of anhydrous aluminum trichloride was charged in three portions, and the mixture was stirred at a temperature of 5 ℃ or lower for 3 hours. The purity was 96%.
Other steps are not changed, if the step (2) is changed into: a total of 160 parts of anhydrous aluminum trichloride was charged at one time, and the temperature was controlled to 5 ℃ or lower, and stirred for 3 hours. The purity was 96.5%.
Example 5
Comparative example, synthesis process: the difference from example 3 is that the other steps are unchanged, if the purification steps are adjusted as follows:
1. dispersing and pulping the prepared 4-chloro-4 '-hydroxybenzophenone by 1000 parts by weight of 1% sodium carbonate solution, washing, centrifuging, dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of 1% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, adding 5 parts by weight of activated carbon into the water phase, heating for decolorization, and performing pressure filtration, wherein the pH value of the filtrate is adjusted to be less than 2 by concentrated hydrochloric acid at 60 ~ 70 ℃ and the purity is obviously reduced to 94%.
2. Dispersing and pulping the prepared 4-chloro-4 '-hydroxybenzophenone by 1000 parts by weight of 3% sodium carbonate solution, washing, centrifuging, dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of 3% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, adding 5 parts by weight of activated carbon into the water phase, heating for decolorization, and carrying out filter pressing, wherein the pH value of the filtrate is adjusted to be less than 2 by concentrated hydrochloric acid at 60 ~ 70 ℃, and the purity is obviously reduced to about 98.7%.
3. If chlorobenzene is not used for extraction, the purity requirement cannot be met.
4. If the product is not decolorized by active carbon, the finished product has color.
5. Although the operation can be carried out by adjusting the weight of the aqueous solution of sodium carbonate and sodium hydroxide, the volume is too small, the operation is difficult, and the washing is not thorough, which may cause variation in purity of the batch.
Example 6
Comparative example, synthesis process the difference from example 3 is that the other steps are not changed, only the temperature is controlled to be slightly higher, and the temperature is raised to 125 ~ 130 ℃ in one step.
The specific synthesis process comprises the following steps: (1) putting 735 parts of chlorobenzene and 150 parts of anisole into a reaction kettle, and cooling to below 8 ℃;
(2) the anhydrous aluminum trichloride of 160 parts in total is added in three batches, each batch is evenly distributed, the temperature is controlled to be below 8 ℃, and the mixture is stirred for 3 hours.
(3) Dropwise adding a mixed solution of 245 parts of parachlorobenzoyl chloride and 120 parts of chlorobenzene, controlling the reaction temperature to be 8 ℃, and finishing the addition within 10 hours;
(4) after the addition, the temperature is maintained at 8 ℃, and the reaction is carried out for 2 hours;
(5) heating to normal temperature, and maintaining the normal temperature for reaction for 3 hours;
(6) adding 150 parts of anhydrous aluminum trichloride at one time, and stirring for 1 hour;
(7) heating to 125 ~ 130 ℃ and reacting for 3 hours at constant temperature;
(9) cooling to below 50 ℃ to prepare for hydrolysis;
(10) adding 2000 parts of water into a hydrolysis kettle, cooling to below 35 ℃, and dropwise adding the reaction liquid, wherein the reaction temperature is not higher than 45 ℃;
(11) after the addition, the reaction is carried out for 1 hour under the condition of heat preservation;
(12) cooling to below 10 ℃, and centrifugally washing to obtain the 4-chloro-4' -hydroxybenzophenone;
(13) dispersing, pulping and washing the prepared 4-chloro-4' -hydroxybenzophenone by 1000 parts by weight of 2% sodium carbonate solution, and then performing centrifugal separation;
(14) dissolving 4-chloro-4' -hydroxybenzophenone by 3000 parts by weight of a 2% sodium hydroxide aqueous solution, adding 200 parts by weight of chlorobenzene for extraction, continuously adding 5 parts by weight of activated carbon into a water phase, heating for decolorization, performing pressure filtration, adjusting the pH value of filtrate to be less than 2 by using concentrated hydrochloric acid at 60 ~ 70 ℃, cooling to below 20 ℃ for precipitation, performing centrifugal separation to obtain a fine product, and controlling the temperature and the time to be combined with each other to achieve the purity of 96%.
Claims (7)
1. A method for synthesizing high-purity 4-chloro-4' -hydroxybenzophenone is characterized by comprising the following steps: the following parts are all parts by weight;
putting 735 parts of chlorobenzene and 150 parts of anisole into a reaction kettle, and cooling to below 5 ℃;
a total of 120 ~ 200 parts of anhydrous aluminum trichloride was charged in three portions, and the mixture was stirred at a temperature of 5 ℃ or lower for 2 ~ 4 hours.
2. Dropwise adding a mixed solution of 245 parts of p-chlorobenzoyl chloride and 120 parts of chlorobenzene, controlling the reaction temperature to be 0 ~ 5 ℃, and finishing the addition within 10 hours;
after the addition, the temperature is maintained at 0 ~ 5 ℃, and the reaction is carried out for 1 ~ 3 hours;
heating to normal temperature, and maintaining the normal temperature for reaction for 1 ~ 3 hours;
adding 150 parts of anhydrous aluminum trichloride at one time, and stirring for 0.5 ~ 2 hours;
heating to 80 ℃, and reacting for 0.5 ~ 1 hours at constant temperature;
then heating to 125 ~ 130 ℃ and reacting for 2 ~ 4 hours at constant temperature;
cooling to below 40 ℃ to prepare for hydrolysis;
adding 2000 parts of water into a hydrolysis kettle, cooling to below 30 ℃, and dropwise adding the reaction liquid, wherein the reaction temperature is not higher than 40 ℃;
after the addition, the reaction is carried out for 0.5 ~ 2 hours under the condition of heat preservation;
cooling to below 10 ℃, centrifuging and washing with water to obtain the 4-chloro-4' -hydroxybenzophenone.
3. The method for synthesizing 4-chloro-4 '-hydroxybenzophenone according to claim 1, further comprising a purification step of dispersing, beating and washing the obtained 4-chloro-4' -hydroxybenzophenone with 1000 parts by weight of a 2% sodium carbonate solution, followed by centrifugation;
the method for synthesizing high-purity 4-chloro-4 '-hydroxybenzophenone according to claim 2, wherein the purification step further comprises, after pulping, washing and centrifuging a sodium carbonate solution, dissolving 4-chloro-4' -hydroxybenzophenone with 3000 parts by weight of a 2% sodium hydroxide solution, adding 200 parts by weight of chlorobenzene for extraction, adding 5 parts by weight of activated carbon into an aqueous phase, heating for decolorization, press-filtering, adjusting the pH value of the filtrate to be less than 2 with concentrated hydrochloric acid at 60 ~ 70 ℃, cooling to below 20 ℃ for precipitation, and centrifuging to separate out a refined product with a purity of more than 99%.
4. The method for synthesizing 4-chloro-4' -hydroxybenzophenone according to claim 3, wherein in the purification step, chlorobenzene is used for 5 times after being extracted and layered, and then the chlorobenzene is rectified and reused.
5. The method for synthesizing 4-chloro-4' -hydroxybenzophenone according to claim 3, wherein the purification step is carried out by absorbing hydrochloric acid tail gas with water.
6. The method for synthesizing 4-chloro-4' -hydroxybenzophenone according to claim 1, wherein the anhydrous aluminum trichloride in the step (2) is 160 parts by weight in total, and is added in three times and evenly distributed.
7. The method for synthesizing 4-chloro-4' -hydroxybenzophenone according to claim 1, wherein the room temperature in the step (2) is 25 ℃.
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| CN116265427A (en) * | 2021-12-16 | 2023-06-20 | 爱生华(苏州)光学有限公司 | Treatment method of 2- (4-benzoyl-3-hydroxyphenoxy) ethyl 2-acrylate kettle residues |
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