CN1696094A - Preparation method of 4,4'-dihydroxybenzophenone - Google Patents

Abstract

A process for preparing the 4,4'-bihydroxybiphenyl methaneone includes mixing phenyl p-hydroxybenzoate with catalyst in organic solvent, heating while stirring, reaction, separating the resultant and recrystallizing.

Description

4, the preparation method of 4'-dihydroxybenzophenone

technical field

The invention belongs to the field of fine organic chemical industry and relates to a preparation method of 4,4'-dihydroxybenzophenone.

Background technique

4,4'-Dihydroxybenzophenone is a chemical and pharmaceutical intermediate, and its structural formula is:

There are many reports on its synthesis, among which Japanese patent JP3123752 reports that p-hydroxybenzoic acid and phenol are used as raw materials, and polyphosphoric acid is directly used as a solvent for simultaneous catalysis to synthesize the target compound. At present, this method is also used in industry. The type of catalyst used in this method is limited, and waste phosphoric acid is difficult to recycle, causing serious environmental pollution and high cost.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies in the prior art and provide a new 4,4'-dihydroxybenzophenone synthesis route and method. The method has relatively simple process, low production cost and high product yield, and is suitable for large-scale industrial production.

The technical solution provided by the present invention is: the preparation method of 4,4'-dihydroxybenzophenone, in the presence of a catalyst, stirring phenyl p-hydroxybenzoate in an organic solvent and heating it up to 70-170°C, keeping the reaction temperature After 3 to 20 hours, the product was separated and recrystallized to obtain 4,4'-dihydroxybenzophenone. Its reaction formula is:

The catalyst used is selected from zinc chloride, aluminum chloride, methanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, polyphosphoric acid, perchloric acid, methanesulfonic acid metal salt, p-toluenesulfonic acid metal salt, trifluoro Metal methanesulfonate, or a mixture of any two or more of the above acids.

The organic solvent used is benzene, toluene, chlorobenzene, nitrobenzene, carbon disulfide, cyclohexane, C ₆ -C ₁₀ hydrocarbons and/or petroleum ether.

The molar ratio of phenyl p-hydroxybenzoate to catalyst is 1:0.1～1.

Phenyl p-hydroxybenzoate is produced by reacting p-acetoxybenzoyl chloride and phenol at 80-140°C in chlorobenzene, or reacting in dichloromethane, chloroform or carbon tetrachloride at 5-40°C to generate p-acetoxybenzene Phenyl formate and phenyl p-acetoxybenzoate can be obtained by removing acetoxy groups in the solvent ammonia and alcohol.

The alcohol used for removing the acetoxy group is methanol, ethanol, propanol or butanol, and the volume ratio of alcohol to ammonia water is 100:5-60.

The above-mentioned p-acetoxybenzoyl chloride reacts with p-hydroxybenzoic acid and an acetylating reagent to generate p-acetoxybenzoic acid, and p-acetoxybenzoic acid undergoes phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride or chlorination Chlorination of sulfoxide gives p-acetoxybenzoyl chloride.

Compared with the prior art, the present invention has the following advantages: (1) utilizes methyl p-hydroxybenzoate rearrangement to prepare 4,4'-dihydroxybenzophenone, broadens the types of available catalysts, and solves the problems of large catalyst consumption, phosphoric acid The waste liquid is difficult to handle, which reduces the production cost and simplifies the process. (2) The yield is high, and it is suitable for large-scale industrial production.

Detailed ways

Example 1

(1) p-acetoxybenzoic acid

Add p-hydroxybenzoic acid and acetic anhydride into a 250ml three-neck flask, stir and add a catalytic amount of concentrated sulfuric acid, heat at 65°C for 2 hours, pour the material into ice water, stir, precipitate solids, filter, and recrystallize ethanol to obtain a white solid p-Acetoxybenzoic acid, yield 93%, mp192-194.

(2) p-Acetoxybenzoyl chloride

Add 28g (0.16mol) of p-acetoxybenzoic acid, 40ml (0.55mol) of thionyl chloride and pyridine (0.06-0.1ml) into a three-necked flask equipped with a stirring and reflux condenser, and heat up to 70-75°C The reaction was stirred for 3h until no gas evolved. After cooling to room temperature, unreacted thionyl chloride was distilled off, and the residue was distilled under reduced pressure to collect fractions at 140-144°C/10.67kPa to obtain 29g (0.15mol) of light yellow oily liquid p-acetoxybenzoyl chloride.

(3) Phenyl p-acetoxybenzoate

Add 15g (0.16mol) of phenol, 23g (0.16mol) of pyridine and dichloromethane (200ml) to the reaction flask under ice-water bath conditions, add 50mL of dichloromethane (200ml) containing 29g (0.15mol) of p-acetoxybenzoyl chloride after stirring for 5min. Chloromethane solution, stirred at room temperature for 18h. Add 60ml of 3mol/L hydrochloric acid to wash, and the organic phase is washed with 50ml of 5% sodium bicarbonate solution and 50ml of water successively, and dried with anhydrous sodium sulfate. The solvent was evaporated, and the remaining yellow solid was decolorized by activated carbon and recrystallized from ethanol to obtain 39 g of white crystals of phenyl p-acetoxybenzoate, with a yield of 95%, and mp82-83°C. FT-IR (KBr, diffuse reflectance) m ^-1 ν _max : 1767 (ν _{c = o} ), 1736 (ν _{c = o} ), 1597, 1493 (ν _{c = c} ); 1269 (ν _co ), 1153 (ν _co ); H'NMR (CDCl ₃ , δ, ppm): 8.24 (d, 2H, J = 11 Hz), 7.43 (m, 2H, J = 12 Hz), 7.26 (m, 5H), 2.43 (s, 3H) ; MS MS (M/Z, M) 256. Element analysis: C70.28, H5, 43.

(4) Phenyl p-hydroxybenzoate

30g (0.12mol) of phenyl p-acetoxybenzoate was dissolved in 100ml of methanol, 30ml of 28% ammonia water was added at 0-5°C, and the reaction was stirred at room temperature for 2.5h. The reactant was poured into 100 grams of crushed ice, extracted with dichloromethane (60ml×3), the organic phases were combined, dried with anhydrous sodium sulfate, filtered, the filtrate was evaporated under reduced pressure to remove dichloromethane, and the residue was recrystallized with ethanol. A white crystal of phenyl p-hydroxybenzoate was obtained, the yield was 92%, and the mp was 184-185°C. FT-IR (KBr, cm ^-1 ): 3402 (ν _c-OH ), 1701 (ν _{c = O} ); 1604, 1586, 1509 (ν _{c = C} ); 1262 (ν _cO ), 1158 (ν _cO ) .H'NMR (DMSO-d, ppm): 10.55 (s, 1H), 8.0 (d, 2H, J=14Hz), 7.46 (m, 2H), 7.28 (t, 1H, J=15Hz), 7.2( d, 2H, J=13Hz), 6.94 (d, 2H, J=14Hz); MS (M/Z, M ⁺ ) 214. Element analysis: C 72.45, H4, 71.

(5) 4,4'-p-dihydroxybenzophenone

21.5g (0.1mol) of phenyl p-hydroxybenzoate and 3.8g (0.04mol) of methanesulfonic acid were dissolved in 100ml of anhydrous carbon disulfide, and the temperature was raised to reflux for 8 hours while stirring. Cool to room temperature, add 20ml of 5% hydrochloric acid to wash, filter, wash the filter cake with 10% sodium bicarbonate solution and water, and recrystallize with ethanol-water (1:4) to obtain the white crystal target compound 4,4'-para Hydroxybenzophenone 20g, yield 93%, mp219～220 ℃. FT-IR (KBr, cm ^-1 ): 3339 (ν _c-OH ), 1628 (ν _{c = O} ); 1595, 1574; 1446 (ν _{c = C} ); 1244 (ν _cO ) 854 (1, 4benzene) ;.H'NMR (acetonr-d ₆ , ppm): 9.1 (s, 2H), 7.71 (d, 4H, J=6Hz), 6.95 (d, 4H, J=6Hz),; MS (M/Z, M ⁺ )214.Element analysis: C72.52, H4,68.

Example 2

The preparation methods of p-acetoxybenzoic acid, p-acetoxybenzoyl chloride, and phenyl p-hydroxybenzoate are the same as in Example 1.

Using chlorobenzene as the solvent instead, reflux reaction for 10 hours to prepare phenyl p-acetoxybenzoate with a yield of 96%.

The ratio of phenyl p-hydroxybenzoate:trifluoromethanesulfonic acid is 1:0.2 (molar ratio), petroleum ether is used as solvent, and the temperature is raised, stirred and refluxed for 10 hours. Wash with 10% sodium bicarbonate solution and water, and recrystallize from methanol-water (1:3, volume ratio) to obtain the target compound 4,4'-p-dihydroxybenzophenone. Yield 98%. mp219～220℃.

Example 3

The preparation methods of p-acetoxybenzoic acid, p-acetoxybenzoyl chloride, and phenyl p-hydroxybenzoate are the same as in Example 1.

Using chlorobenzene as the solvent instead, reflux reaction for 10 hours to prepare phenyl p-acetoxybenzoate with a yield of 96%.

Phenyl p-hydroxybenzoate: chromium trifluoromethanesulfonate at a ratio of 1:0.15 (molar ratio), cyclohexane as a solvent, and the temperature was raised to stir and reflux for 8 hours. Wash with 10% sodium bicarbonate solution and water, and recrystallize from methanol-water (1:3, volume ratio) to obtain the target compound 4,4'-p-dihydroxybenzophenone. Yield 99%. mp219～220℃.

Example 4

The preparation method of p-acetoxybenzoic acid is the same as in Example 1.

Preparation of p-acetoxybenzoyl chloride:

Add 28 g (0.16 mol) of p-acetoxybenzoic acid and 40 ml of phosphorus trichloride into a three-necked flask equipped with a stirring and reflux condenser, raise the temperature to 70-75°C and stir for 3 hours. Unreacted phosphorus trichloride and generated phosphorus oxychloride were distilled off. The residue was distilled under reduced pressure to collect fractions at 140-144°C/10.67kPa to obtain 28 g of light yellow oily liquid p-acetoxybenzoyl chloride.

The preparation of phenyl p-acetoxybenzoate is with embodiment 2.

Preparation of phenyl p-hydroxybenzoate:

30 g (0.12 mol) of phenyl p-acetoxybenzoate was dissolved in 100 ml of a mixed solvent of ammonia water and n-butanol (the weight ratio of ammonia water: n-butanol was 25:100), and the reaction was stirred at room temperature for 2.5 h. The reactant was poured into 100ml of water and filtered. Recrystallized with methanol to obtain white crystals of phenyl p-hydroxybenzoate with a yield of 93% and mp184-185°C.

4, the preparation of 4'-p-dihydroxybenzophenone:

Phenyl p-hydroxybenzoate: methanesulfonic acid and polyphosphoric acid are 1: 0.3 (molar ratio); the volume ratio of methanesulfonic acid and polyphosphoric acid is 5: 1; cyclohexane is used as solvent, and the temperature is raised and stirred and refluxed for 10 hours , filtered, washed with 10% sodium bicarbonate solution and water, and recrystallized from methanol-water (1:3) to obtain the target compound 4,4'-p-dihydroxybenzophenone. Yield 95%. mp219～220℃.

The purity of the synthesized 4,4'-p-dihydroxybenzophenone is above 99.7%.

Claims (7)

1.4, the preparation method of 4'-dihydroxybenzophenone is characterized in that: in the presence of a catalyst, the phenyl p-hydroxybenzoate is stirred and heated up to 70-170°C in an organic solvent, and the reaction temperature is kept for 3-20 hours , Separate the product and recrystallize to obtain 4,4'-dihydroxybenzophenone. 2. The preparation method according to claim 1, characterized in that: the catalyst used is selected from zinc chloride, aluminum chloride, methanesulfonic acid, p-toluenesulfonic acid, trifluoromethanesulfonic acid, polyphosphoric acid, perchloric acid , metal methanesulfonate, metal p-toluenesulfonate, metal trifluoromethanesulfonate, or a mixture of any two or more of the above acids. 3. The preparation method according to claim 1 or 2, characterized in that: the organic solvent used is benzene, toluene, chlorobenzene, nitrobenzene, carbon disulfide, cyclohexane, C6 _{～ C10} hydrocarbons and/or petroleum ether. 4. according to the described preparation method of claim 1 or 2, it is characterized in that: the mol ratio of phenyl p-hydroxybenzoate and catalyst is 1: 0.1～1. 5. according to the described preparation method of claim 1 or 2, it is characterized in that: phenyl p-hydroxybenzoate is reacted at 80～140 ℃ of chlorobenzene by p-acetoxybenzoyl chloride and phenol, or in dichloromethane, three Chloromethane or carbon tetrachloride reacts at 5-40°C to produce phenyl p-acetoxybenzoate, which can be obtained by removing the acetoxy group in the solvent ammonia and alcohol. 6. The preparation method according to claim 5, characterized in that: the alcohol used for removing the acetoxy group is methanol, ethanol, propanol or butanol, and the volume ratio of alcohol to ammonia water is 100:5-60. 7. preparation method according to claim 5 is characterized in that: p-acetoxybenzoyl chloride generates p-acetoxybenzoic acid with p-hydroxybenzoic acid and acetylating reagent reaction, and p-acetoxybenzoic acid is treated with trichloride Oxyphosphorus, phosphorus trichloride, phosphorus pentachloride or thionyl chloride can be chlorinated to obtain p-acetoxybenzoyl chloride.