CN108409548B - Preparation method of 2, 2' -dihydroxy benzophenone compound - Google Patents
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Abstract
The application relates to a preparation method of a 2, 2' -dihydroxy benzophenone compound, belonging to the technical field of ketone acyclic compound synthesis. The preparation method comprises the steps of taking 5-alkyl-3- [ 5-alkyl-2-hydroxyphenyl ] benzofuran-2- (3H) -ketone as a raw material, adding an anhydrous alkali catalyst after a solvent is dissolved, and introducing oxygen or air for oxidation reaction. The method is applied to the preparation of the dihydroxy benzophenone compound, and has the advantages of simple steps, green synthesis, no pollution, high yield and the like.
Description
Technical Field
The application relates to a preparation method of a 2, 2' -dihydroxy benzophenone compound, belonging to the technical field of ketone acyclic compound synthesis.
Background
Benzophenone compounds have been widely used in the fields of medicine, pesticide, plastics, dye, electronic chemical industry, daily chemical industry, and the like. With the difference of the types, the number and the positions of the substituents on the benzene rings on two sides of the carbonyl group, the family members of the benzophenone compound are very huge, and the compounds with the hydroxyl on the benzene ring are also commonly used as antioxidants. Therefore, the method has important significance for the synthesis research of the compounds.
The main synthetic methods at present are: Fielder-Crafts reaction, transition metal catalysis, oxidation, photocatalysis, and the like, as follows:
1. benzene and benzoyl chloride are used as raw materials, anhydrous aluminum trichloride is used as a catalyst, heating and refluxing are carried out for 3 hours, and the final yield is 71.2%.
The Fielder-Crafts acylation reaction needs a large amount of soluble Lewis acid or inorganic strong acid, the reaction condition is severe, the selectivity is poor, a large amount of industrial three wastes are generated, the environment is polluted, and the cost is increased.
2. With [ Rh (CHCH)2)2Cl]2And P (t-Bu)3As a catalyst, aromatic aldehyde and aryl potassium trifluoroborate are used as raw materials to react under a mild condition to obtain the benzophenone compound, and the yield is 73-93%.
Although the metal catalytic method has high yield, the rhodium catalyst is expensive and is not suitable for industrial production.
3. Taking benzofuranone compounds as raw materials, carrying out alkaline hydrolysis on lactone rings in aqueous solution of sodium hydroxide, and then carrying out alkaline hydrolysis on the lactone rings in K3[Fe(CN)]To obtain the benzophenone compound under the oxidation action of the alcohol.
Although the oxidation method is simple to operate, the yield is only 24.8 percent according to the literature report, and alkaline industrial wastewater exists.
4. Benzofuranone compounds are used as raw materials and oxidized by potassium permanganate under alkaline conditions to obtain the benzophenone compounds.
5. Dissolving phenanthrene ketone compounds serving as raw materials in benzene, purging nitrogen for 20min, then carrying out 2h under illumination, monitoring the reaction by TLC, distilling and recovering a solvent after the reaction is completed, and passing through a column to obtain a product.
The photocatalysis method is safe and pollution-free, accords with the concept of green chemistry, but has complex operation, and needs to pass through a column, and the yield is 60 percent.
6. 2, 2' -dihydroxy diphenylmethane compound as raw material and pyridine as solvent are reacted with acetic anhydride to produce corresponding diacetate, which is then treated with CrO3Oxidizing to obtain 2,2 '-diacetate benzophenone compound, and hydrolyzing under alkaline condition to obtain 2, 2' -dihydroxy benzophenone compound.
The method has the disadvantages of complicated operation, multiple steps and low oxidation yield of only 33 percent in the second step.
7. Salicylaldehyde is used as a raw material, and a 2, 2' -dihydroxy benzophenone compound is obtained through one-step reaction under the catalysis of metal Rh.
The method has simple reaction and only one-step operation, but the metal catalyst is expensive, the reaction time is long, and the yield is only 52 percent.
8. Using 2-methoxy aryl bromide and 2-methoxy benzaldehyde as raw materials, reacting under the action of Mg to obtain a benzo compound, and then reacting with K in the presence of DMF2Cr2O7Oxidizing to obtain 2, 2' -dimethyl ether benzophenone compound, and finally adding BBr3Is demethylated to obtain the 2, 2' -dihydroxy benzophenone compound.
The method has multiple steps, wide related reagents and bromine-containing industrial wastewater.
9. 2-ketophenol derivatives are used as raw materials to react with Grignard reagents to prepare the 2, 2' -dihydroxy benzophenone compound in one step, and the yield is 58-72%.
The method is simple to operate, only needs one-step reaction, but has high requirements on raw materials and expensive Grignard reagents.
The present application was made based on this.
Disclosure of Invention
Aiming at the defects in the synthesis of the conventional ketone compound, the application provides a preparation method for synthesizing a green and pollution-free 2,2 '-dihydroxy benzophenone compound with high yield, which comprises the steps of taking 5-alkyl-3- [ 5-alkyl-2-hydroxyphenyl ] benzofuran-2- (3H) -one (lactone, structure II) as a raw material, adding an anhydrous base catalyst after a solvent is dissolved, and introducing oxygen or air to perform an oxidation reaction to synthesize a crude product (structure I) of the 2, 2' -dihydroxy benzophenone compound, wherein the liquid phase content of the crude product is more than 95 percent, the oxidation reaction yield is 88-92 percent, and the solvent is used for dissolving the raw material but does not react with the raw material; the reaction formula of the raw material oxidation reaction is expressed as follows:
R1、R2are all alkyl groups.
Further, as preferable:
the solvent is any one of ethyl acetate, tetrahydrofuran and methanol, and the solvent selected by the method is inert, so that the solvent has good solubility, does not react with the raw materials, and does not consume the raw materials to cause unnecessary loss. More preferably, the solvent is tetrahydrofuran, and the amount of the solvent is 4-8 times, preferably 5-6 times of the mass of the raw materials.
The anhydrous alkali catalyst is organic or inorganic alkali. More preferably, the anhydrous base catalyst is an organic base such as diethylamine or triethylamine, and more preferably triethylamine.
The R is1Is methyl, ethyl, isopropyl or tert-butyl; r2Is methyl, ethyl, isopropyl or tert-butyl; r1And R2The same or different.
In the oxidation reaction, the reaction temperature is 15-45 ℃, and the ventilation quantity is 0.01-1 mol/h. More preferably, in the oxidation reaction, the reaction temperature is 25-35 ℃, and the ventilation quantity is 0.05-0.2 mol/h.
The oxidation reaction is followed by a purification process: and dissolving the oxidation reactant by using dichloromethane, cleaning the washing liquid to be below neutral, and evaporating the organic layer to dryness to obtain a finished product.
The invention has the following beneficial effects:
(1) the invention provides a novel method for preparing 2, 2' -dihydroxy benzophenone compounds.
(2) Compared with other preparation methods, the method for preparing the 2, 2' -dihydroxy benzophenone compound by one step through oxygen or air oxidation has high purity (more than 95 percent) and high yield (88 to 92 percent).
(3) The oxidant used in the invention is oxygen and air, which is cheap and environment-friendly; the solvent used in the invention can be recycled after being recovered, and accords with the concept of green chemistry.
The method has the advantages of simple operation, easily obtained raw materials and easy realization of industrialization.
Drawings
FIGS. 1A, 1B, 1C, 1D, 1E in sequence are the products of example 11HNMR spectrum,13CNMR spectrum, DEPT135 spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 2A, 2B, 2C, 2D, 2E in sequence are for the product of example 21HNMR spectrum,13CNMR spectrum, DEPT135 spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 3A, 3B, 3C, 3D, 3E are, in sequence, the products of example 31HNMR spectrum,13CNMR spectrum, DEPT135 spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 4A, 4B, 4C, 4D are, in sequence, the products of example 41HNMR spectrum,13CNMR spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 5A, 5B, 5C, 5D, 5E are, in sequence, the products of example 51HNMR spectrum,13CNMR spectrum, DEPT135 spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 6A, 6B, 6C, 6D, 6E are, in sequence, the products of example 61HNMR spectrum,13CNMR spectrum, DEPT135 spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 7A, 7B, 7C, 7D, 7E in sequence are for the product of example 71HNMR spectrum,13CNMR spectrum, DEPT135 spectrum, GC-MS total ion chromatogram and FT-IR infrared spectrogram;
FIGS. 8A, 8B, 8C, 8D, 8E in sequence are for the product of example 81HNMR spectrum,13CNMR spectra, DEPT135 spectra, GC-MS total ion chromatograms, and FT-IR infrared spectrograms.
Detailed Description
Analytical instrumentation and equipment used in the following examples: gas chromatography, MS5973N-GC6890N (Agilent, USA); nuclear magnetic resonance apparatus, AVANCE DMXIII 400M (TMS internal standard, Bruker Corp.); high performance liquid chromatograph: agilent Technologies 1200 Series; infrared spectrometer, NICOLET 360FT-IR (Nikko instruments, USA).
In the following examples, examples 1 to 4 are specific examples of preparation of lactone as a raw material, and methyl, ethyl, isopropyl and tert-butyl are respectively selected as representative alkyl groups; examples 5 to 8 were carried out under the same conditions using methyl lactone, ethyl lactone, propyl lactone, and butyl lactone as raw materials to prepare 2, 2' -dihydroxybenzophenone compounds.
Example 1: preparation of 5-methyl-3- [ 5-methyl-2-hydroxyphenyl ] benzofuran-2- (3-hydro) -one (p-methyllactone)
Placing 21.6g of p-methylphenol (0.2 mol), 9.2g of glyoxylic acid monohydrate (0.1 mol) and 0.3 g of p-toluenesulfonic acid into a 500ml three-neck flask, adding 200ml of toluene, heating to dissolve completely, carrying out magnetic stirring and water-carrying reflux reaction for 6h, carrying out liquid phase tracking reaction, evaporating the solvent to obtain a yellow brown solid after the reaction is completed, and then recrystallizing with methanol to obtain 22.5g of a light yellow solid, namely 5-methyl-3- [ 5-methyl-2-hydroxyphenyl ] benzofuran-2- (3H) -one, namely methyl lactone, wherein the liquid phase purity of the methyl lactone is 98.3%, and the yield is 90.1%.
Product structure validation (see FIGS. 1A-1E):
1HNMR(,ppm,400MHz,CDCl3):2.239(s,3H,CH3)；2.321(s,3H,CH3)；4.983(s,1H)；5.059(s,1H)；6.750(d,1H,J＝8.4,Ar-H)；6.855(d,1H,J＝1.2,Ar-H)；6.987(dd,2H,J1＝1.6,J2＝8.4,Ar-H)；7.051(d,1H,J＝8.4,Ar-H)；7.133(d,1H,J＝8,Ar-H)；
13CNMR(,ppm,100MHz,CDCl3):20.5；21.1；46.2；110.4；117.0；122.4；125.5；126.7；129.5；129.9；130.1；130.71；134.11；151.5；152.0；177.4.
DEPT135(,ppm,100MHz,CDCl3):20.5；21.1；46.2；110.4；117.0；125.5；129.5；129.9；130.1.
GC-MS(m/e):39,51,63,77,91,115,165,181,195,209(100％),225,254.
FT-IR(cm-1):3410,3021,2917,1793,1614,1488,1208.
example 2: preparation of 5-ethyl-3- [ 5-ethyl-2-hydroxyphenyl ] benzofuran-2- (3-hydro) -one (p-ethyl lactone)
24.4g of p-ethylphenol (0.2 mol), 9.2g of glyoxylic acid monohydrate (0.1 mol) and 0.3 g of p-toluenesulfonic acid are placed in a 500ml three-neck flask, 200ml of toluene is added, the mixture is heated to be completely dissolved, then the mixture is stirred magnetically and refluxed with water for 6 hours, the liquid phase tracking reaction is carried out, after the reaction is completed, the solvent is evaporated to dryness to obtain a yellow brown solid, and then the yellow brown solid is recrystallized by using ethanol to obtain 25.6g of a light yellow solid, namely 5-ethyl-3- [ 5-ethyl-2-hydroxyphenyl ] benzofuran-2- (3H) -one, namely ethyl lactone, wherein the liquid phase purity of the ethyl lactone is 98.5%, and the yield is 92.0%.
Product structure validation (see FIGS. 2A-2E):
1HNMR(,ppm,400MHz,CDCl3):1.182(m,6H,CH3)；2.536(q,2H)；2.613(q,2H)；4.679(s,1H)；5.081(s,1H).6.763(d,1H,J＝8,Ar-H)；6.873(d,1H,J＝2,Ar-H)；7.002(dd,2H,J1＝2,J2＝8.4,Ar-H)；7.074(d,1H,J＝8.4,Ar-H)；7.157(d,1H,J＝8.4,Ar-H)；
13CNMR(,ppm,100MHz,CDCl3):15.7；15.9；28.0；28.6；46.3；110.4；117.0；122.3；124.4；126.8；128.3；128.8；128.9；137.0；140.7；151.8；152.1；177.6.
DEPT135(,ppm,100MHz,CDCl3):15.7；15.9；28.0(-)；28.6(-)；46.34；110.4；117.0；124.4；128.3；128.8；128.9.
GC-MS(m/e)：51,65,77,91,115,152,165,181,194,210,225(100％),237,253,282.
FT-IR(cm-1):3366,2965,2923,2887,1788,1612,1483,1340,1287,1202,1143.
example 3: preparation of 5-isopropyl-3- [ 5-isopropyl-2-hydroxyphenyl ] benzofuran-2- (3-hydro) -one (p-isopropyllactone)
27.2g of p-isopropylphenol (0.2 mol), 9.2g of glyoxylic acid monohydrate (0.1 mol) and 0.3 g of p-toluenesulfonic acid are placed in a 500ml three-neck flask, 200ml of toluene is added, the mixture is heated to be completely dissolved, then the mixture is stirred magnetically and refluxed with water for 6 hours, the liquid phase tracking reaction is carried out, after the reaction is completed, the solvent is evaporated to dryness to obtain a yellow brown solid, and then the yellow brown solid is recrystallized by ethanol to obtain 27.3g of a light yellow solid, namely 5-isopropyl-3- [ 5-isopropyl-2-hydroxyphenyl ] benzofuran-2- (3H) -one, namely propyl lactone, wherein the liquid phase purity of the propyl lactone is 98.7 percent, and the yield is 89.2 percent.
Product structure validation (see FIGS. 3A-3E):
1HNMR(,ppm,400MHz,CDCl3):1.170(m,6H)；1.227(d,6H,J＝6.8)；2.798(m,1H)；2.903(m,1H)；5.135(s,1H)；6.818(d,1H,J＝8.4,Ar-H)；6.875(d,1H,J＝2.4,Ar-H)；7.057(dd,1H,J1＝2,J2＝8,Ar-H)；7.089(s,1H,Ar-H)；7.110(s,1H,Ar-H)；7.213(dd,1H,J1＝1.6,J2＝6.4,Ar-H)；
13CNMR(,ppm,100MHz,CDCl3):23.9；24.2；24.3；24.3；33.3；33.9；46.4；110.5；117.3；122.1；123.2；126.3；127.0；127.1；127.5；141.8；145.4；152.0；152.3；177.7.
DEPT135(,ppm,100MHz,CDCl3):23.9；24.2；24.3；24.3；33.3；33.9；46.4；110.5；117.3；123.2；127.0；127.1；127.5.
GC-MS(m/e):43,65,77,91,126,140,165,197,223,239(100％),249,268,295,310.
FT-IR(cm-1):3453,3345,2959,2869,1777,1611,1512,1484,1299.
example 4: preparation of 5-tert-butyl-3- [ 5-tert-butyl-2-hydroxyphenyl ] benzofuran-2- (3-hydro) -one (p-tert-butyl lactone)
30.0g of p-tert-butylphenol (0.2 mol), 9.2g of glyoxylic acid monohydrate (0.1 mol) and 0.3 g of p-toluenesulfonic acid are placed in a 500ml three-neck flask, 200ml of toluene is added, after heating and complete dissolution, the mixture is stirred magnetically and refluxed with water for 6 hours, liquid phase tracking reaction is carried out, after the reaction is completed, the solvent is evaporated to dryness to obtain yellow brown solid, and then methanol is used for recrystallization to obtain light yellow solid 30.1g, namely 5-tert-butyl-3- [ 5-tert-butyl-2-hydroxyphenyl ] benzofuran-2- (3H) -one, namely butyl lactone for short, wherein the purity of the liquid phase of the butyl lactone is 98.5%, and the yield is 90.4%.
Product structure validation (see FIGS. 4A-4D):
1HNMR(,ppm,400MHz,CDCl3):1.220(s,9H)；1.304(s,9H)；5.195(s,1H)；6.819(s,1H)；6.830(d,1H,J＝8.4,Ar-H)；7.002(d,1H,J＝2.4,Ar-H)；7.109(d,1H,J＝8.4,Ar-H)；7.197(dd,1H,J1＝2.4,J2＝8.4,Ar-H)；7.279(s,1H,Ar-H)；7.391(dd,1H,J1＝1.6,J2＝8.8,Ar-H)；
13CNMR(,ppm,100MHz,CDCl3):31.5；31.6；34.2；34.8；46.4；110.2；117.1；121.5；122.6；125.7；125.8；126.0；126.5；144.0；147.8；152.1；178.2.
GC-MS(m/e):41,57,77,91,112,140,154,165,197,226,239,253(100％),267,282,323,338.
FT-IR(cm-1):3381,2959,2866,1775,1626,1513,1486,1421,1363,1230.
example 5: preparation of 2,2 '-dihydroxy-5, 5' -dimethyl benzophenone
Weighing 2.54g of p-methyl lactone (0.01 mol, can be selected from the raw materials prepared in example 1, and can also be purchased) into a 100ml single-mouth bottle, adding 15ml of tetrahydrofuran, adding 1ml of triethylamine after completely dissolving under magnetic stirring, introducing oxygen (with the ventilation amount of about 0.1 mol/h) at 35 ℃ for stirring reaction, after 4 hours, completely reacting in liquid phase detection, and evaporating the tetrahydrofuran under reduced pressure at normal temperature to obtain a viscous crude product. Adding 10ml dichloromethane for complete dissolution, washing with 5% hydrochloric acid solution to weak acidity, layering, evaporating organic layer to dryness to obtain yellow powdery solid 2.12g, liquid phase purity 95.6%, and yield 91.8%.
Product structure validation (see FIGS. 5A-5E):
1HNMR(,ppm,400MHz,CDCl3):2.307(s,6H,CH3)；6.986(d,1H,J＝8.8,Ar-H)；7.321(dd,1H,J1＝1.6,J2＝8.4,Ar-H)；7.385(s,1H,Ar-H)；10.387(s,2H).
13CNMR(,ppm,100MHz,CDCl3):20.6；118.3；119.7；128.0；132.7；136.8；159.5；202.4.
DEPT135(,ppm,100MHz,CDCl3):20.6；118.3；132.7；136.8.
GC-MS(m/e)：53,63,77,91,107,120,135(100％),152,225,242.
FT-IR(cm-1):3181,3033,2920,2854,1626,1580,1480,1199.
example 6: preparation of 2,2 '-dihydroxy-5, 5' -diethyl benzophenone
Weighing 2.82g of p-ethyl lactone (0.01 mol, can be selected from the raw materials prepared in example 2, or can be purchased) into a 100ml single-mouth bottle, adding 15ml of tetrahydrofuran, adding 1ml of triethylamine after completely dissolving under magnetic stirring, introducing oxygen (the ventilation amount is about 0.1 mol/h) at 35 ℃ for stirring reaction, after 4h, completely reacting in liquid phase detection, and evaporating the tetrahydrofuran under reduced pressure at normal temperature to obtain a viscous crude product. Adding 10ml dichloromethane for complete dissolution, washing with 5% hydrochloric acid solution to weak acidity, layering, evaporating organic layer to dryness to obtain yellow powdery solid 2.37g, liquid phase purity 96.3%, and yield 91.2%.
Product structure validation (see FIGS. 6A-6E):
1HNMR(,ppm,400MHz,CDCl3):1.218(t,6H,J＝7.6Hz,2-CH3),2.574-2.631(q,4H)；7.012(d,1H,J＝8.4,Ar-H)；7.355(dd,1H,J1＝2.4,J2＝8.4,Ar-H)；7.427(d,1H,J＝2.0,Ar-H)；10.444(s,2H).
13CNMR(,ppm,100MHz,CDCl3):15.7；27.9；118.3；119.7；131.8；134.4；135.8；159.8；202.4.
DEPT135(,ppm,100MHz,CDCl3):15.7；27.9(-)；118.3；131.8；135.8.
GC-MS(m/e)：29,39,53,65,77,91,107,120,133,149(100％),165,181,197,213,225,241,253,270.
FT-IR(cm-1):3194,3054,2959,2925,1798,1617,1574,1480,1350,1256,1231,1202,1180.
example 7: preparation of 2,2 '-dihydroxy-5, 5' -diisopropyl benzophenone
Weighing 3.10g of p-isopropyl lactone (0.01 mol, can be selected from the raw materials prepared in example 3, or can be purchased) into a 100ml single-neck bottle, adding 15ml of tetrahydrofuran, adding 1ml of triethylamine after completely dissolving under magnetic stirring, introducing oxygen (with the ventilation amount of about 0.1 mol/h) at 35 ℃ for stirring reaction, detecting the reaction in a liquid phase after 4h, and evaporating the tetrahydrofuran under reduced pressure at normal temperature to obtain a viscous crude product. Adding 10ml dichloromethane for complete dissolution, washing with 5% hydrochloric acid solution to weak acidity, layering, evaporating organic layer to dryness to obtain yellow powdery solid 2.62g, liquid phase purity 97.1%, and yield 90.3%.
Product structure validation (see FIGS. 7A-7E):
1HNMR(,ppm,400MHz,CDCl3):1.229(d,12H,J＝6.8Hz,4CH3),2.818-2.922(m,2H,2-CH-)；7.026(d,1H,J＝8.4,Ar-H)；7.395(dd,1H,J1＝2.4,J2＝8.4,Ar-H)；7.453(d,1H,J＝2.0,Ar-H)；10.484(s,2H).
13CNMR(,ppm,100MHz,CDCl3):24.0,33.3,118.3,119.6,130.3,134.7,139.1,159.9,202.6.
DEPT135(,ppm,100MHz,CDCl3):24.0,33.3,118.3,130.3,134.7.
GC-MS(m/e):41,53,65,77,91,105,120,134,147(100％),163,197,213,239,255,281,298.
FT-IR(cm-1):2962,1629,1574,1482,1348,1264,1189.
example 8: preparation of 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone
Weighing 3.38g of p-tert-butyl lactone (0.01 mol, which can be selected from the raw materials prepared in example 4 or purchased) into a 100ml single-neck bottle, adding 15ml of tetrahydrofuran, adding 1ml of triethylamine after completely dissolving under magnetic stirring, introducing oxygen (with the ventilation amount of about 0.1 mol/h) at 35 ℃ for stirring reaction, after 4h, detecting the reaction in a liquid phase, and completely reacting, and evaporating the tetrahydrofuran under reduced pressure at normal temperature to obtain a viscous crude product. Adding 10ml dichloromethane for complete dissolution, washing with 5% hydrochloric acid solution to weak acidity, layering, evaporating organic layer to dryness to obtain yellow powdery solid 2.76g, liquid phase purity 95.5%, and yield 88.5%.
Product structure validation (see FIGS. 8A-8E):
1HNMR(,ppm,400MHz,CDCl3):1.324(s,18H,6CH3),7.073(d,2H,Ar-H)；7.594-7.624(m,4H,Ar-H)；10.508(s,2H).
13CNMR(,ppm,100MHz,CDCl3):31.4,34.2,118.2,119.4,129.2,133.5,141.5,159.6,202.9,
DEPT135(,ppm,100MHz,CDCl3):31.4,118.2,129.2,133.5,
GC-MS(m/e):41,57,79,91,105,120,134,148,161(100％),177,255,269,311,326.
FT-IR(cm-1):2956,1629,1605,1504,1422,1377,1271.
the embodiment takes the synthesized lactone as a raw material for reaction, and in the synthesis process, anhydrous alkali is taken as a catalyst, so that the hydrolysis side reaction caused by a water system is avoided, and the purity and the yield of the product are obviously improved; meanwhile, the inert solvent, particularly the inert organic solvent, is used, and the solvent does not react with the raw materials chemically, but only dissolves the raw materials, so that the combination efficiency of the raw materials and oxygen is improved, the reaction efficiency is good, and the reaction period is short.
The following single-factor experiments were conducted on the main factors in the reaction, i.e., reaction temperature, catalyst system, and solvent system, respectively, to obtain preferred embodiments.
Examples 9 to 14: preparation of 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone at different temperatures
In this series of examples, p-tert-butyl lactone is used as a raw material to synthesize 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone, the charging amount, the charging sequence, the solvent, the catalyst and the reaction time are the same as those in example 8, and the influence of the reaction temperature on the finished product is determined, which is specifically shown in table 1.
TABLE 1 comparison table of the synthetic effect under different reaction temperature conditions
| Examples | Reaction temperature (. degree.C.) | Content (%) | Product quantity (gram) | Yield (%) |
| 9 | 5 | 73.6 | 2.02 | 62.1 |
| 10 | 15 | 88.3 | 2.69 | 82.6 |
| 11 | 25 | 95.3 | 2.98 | 91.3 |
| 12 | 35 | 95.6 | 3.00 | 92.0 |
| 13 | 45 | 92.3 | 2.77 | 85.1 |
| 14 | 55 | 88.7 | 2.55 | 78.2 |
The reaction temperature is the basic condition for the reaction, and if the reaction temperature is too low, the reaction activity is affected (for example, when the temperature is lower than 5 ℃ in table 1), so that the yield is low; along with the increasing of the reaction temperature, when the temperature exceeds 15 ℃, the yield increase amplitude is obviously improved, and particularly when the temperature reaches 25-35 ℃, the reaction efficiency and the yield reach better states under the same other conditions; the yield is not greatly affected by the continuous temperature rise. The temperature is controlled to be between 15 and 45 ℃ in consideration of comprehensive cost and energy consumption, and the reaction temperature is controlled to be between 25 and 35 ℃ in particular.
Examples 15 to 22: preparation of 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone by using different catalysts
Series of examples 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone was synthesized from p-tert-butyl lactone, and the amount of charge, the order of charge, the solvent, the reaction temperature and the reaction time were the same as those in example 8, with the difference of the reaction catalyst. The results are shown in Table 2.
TABLE 2 comparison of the results obtained in the synthesis with different catalysts
| Examples | Catalyst and process for preparing same | Content (%) | Product quantity (gram) | Yield (%) |
| 15 | Lithium amide | 88.6 | 2.69 | 82.6 |
| 16 | Triethylamine | 95.6 | 3.00 | 92.0 |
| 17 | Diethylamine | 93.6 | 2.92 | 89.6 |
| 18 | Sodium ethoxide | 88.6 | 2.62 | 80.3 |
| 19 | Sodium carbonate | 94.2 | 2.83 | 87.7 |
| 20 | Sodium bicarbonate | 93.2 | 2.89 | 88.6 |
| 21 | Sodium hydroxide | 12.3 | - | - |
| 22 | Aqueous ammonia | 16.3 | - | - |
The catalyst is a key factor in the reaction, and it can be seen that the commonly used catalyst systems fall into two broad categories: the method is convenient and convenient in the way that the aqueous system such as document 3 takes hydrolysis reaction as a part of the reaction and then is matched with subsequent reaction to synthesize the final product, but for the reaction system of the application, the aqueous system can cause hydrolysis side reaction which is not beneficial to the reaction and can reduce the yield, so that the synthesis rate in document 3 is basically kept about 20%; document 1, as a representative of the existing anhydrous system, requires a large amount of soluble lewis acid or strong inorganic acid to participate in the reaction, and has severe reaction conditions and poor selectivity, and generates a large amount of industrial three wastes, thereby polluting the environment and increasing the cost; the anhydrous alkali has the advantages of mild reaction, excellent selectivity, small using amount and reduced cost.
Therefore, the catalyst is matched with the inert organic solvent, so that the high-efficiency catalytic action is realized, and the reaction yield is effectively improved.
In the above embodiment, the case that ammonia water and inorganic strong base sodium hydroxide are used as catalysts is also listed, and research shows that in the presence of water, a large number of side reactions exist, many peaks are mixed in a liquid chromatogram, and the yield of a target product is low; the strong base sodium hydroxide influences the stability of phenolic hydroxyl, the reaction condition violently promotes the progress of a large number of side reactions, and the yield is low, so that anhydrous weak base-triethylamine is preferred.
Examples 23 to 26: preparation of 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone by using different solvents
In this series of examples, p-tert-butyl lactone was used as a raw material to synthesize 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone, and the amount of the charged material, the order of charging, the catalytic base, the reaction temperature and the reaction time were the same as those in example 8, except that the reaction solvent was used, and the results are shown in table 3.
TABLE 3 comparison of the results obtained when the synthesis is carried out using different reaction solvents
| Examples | Solvent(s) | Content (%) | Product quantity (gram) | Yield (%) |
| 23 | Ethyl acetate | 95.4 | 2.97 | 90.6 |
| 24 | Methylene dichloride | 91.6 | 2.92 | 88.9 |
| 25 | Tetrahydrofuran (THF) | 95.6 | 3.00 | 92.0 |
| 26 | Methanol | 93.8 | 2.96 | 90.2 |
| 27 | Dichloroethane | 89.1 | 2.78 | 79.2 |
The whole anhydrous reaction process that is of this application, solvent select for use inert organic solvent, have not only guaranteed its and raw materials not react, have still guaranteed to have good solubility to the solvent, and when oxygen or air admission oxidation reaction, raw materials all have good contact with catalyst, oxygen, have provided the atmosphere of sufficient reaction for oxidation reaction, have fundamentally guaranteed reaction efficiency.
Examples 28 to 33: preparation of 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone by using different oxidants
In this series of examples, p-tert-butyl lactone was used as a raw material to synthesize 2,2 '-dihydroxy-5, 5' -di-tert-butyl benzophenone, and the amount of charge, the order of charge, the reaction temperature and the reaction time were the same as those in example 8, except that the flow rate of oxygen was changed, and the results are shown in Table 4.
TABLE 4 Effect of different aeration on the Synthesis
| Examples | Air flow (mol/h) | Content (%) | Product quantity (gram) | Yield (%) |
| 28 | 0.01 | 92.3 | 2.90 | 88.8 |
| 29 | 0.05 | 95.1 | 2.93 | 89.8 |
| 30 | 0.1 | 95.4 | 2.99 | 91.9 |
| 31 | 0.2 | 95.5 | 3.00 | 92.0 |
| 32 | 1 | 95.6 | 3.00 | 92.0 |
| 33 | 10 | 95.6 | 3.01 | 92.0 |
In the present application, anhydrous base is used as a catalyst, and in the background art, reference 3 is K3[Fe(CN)]As an oxidizing agent, potassium permanganate is used as an oxidizing agent in document 4, and CrO is used in document 63As oxidizing agent, document 8 by K2Cr2O7Compared with the prior art, the method has the advantages that oxygen or air is used as the oxidant, so that the introduction of heavy metals such as in the above documents is avoided, and pollution-free preparation process is realized; meanwhile, table 4 also provides several sets of parallel tests for carrying out experiments on the ventilation rate, and the results show that the requirements of the oxidation reaction can be met when the ventilation rate is controlled to be 0.01-1 mol/h; especially, when the ventilation amount is 0.05-0.2mol/h, the raw material and the oxygen are fully oxidized and reacted under the premise that the oxidant and the raw material are fully contacted.
Comparative example 1: with 3-phenyl-3H-1-benzofuran-2-one (formula X)1) Experiment for preparing 2-hydroxybenzophenone
Weighing 2.10g (0.01 mol) of 3-phenyl-3H-1-benzofuran-2-one into a 100ml three-necked flask, adding 15ml of tetrahydrofuran, adding 1ml of triethylamine after completely dissolving under magnetic stirring, introducing oxygen (with the ventilation amount of about 0.1 mol/H) at 35 ℃ for stirring reaction, detecting no target product in a liquid phase after 4H, heating to 60 ℃ for reaction for 4H, and still not generating the target product.
Comparative example 2: with 3- (4' -hydroxyphenyl) -3H-1-benzofuran-2-one (formula X)2) Experiment for preparing 2, 4' -dihydroxy benzophenone
Weighing 2.26g (0.01 mol) of 3- (4' -hydroxyphenyl) -3H-1-benzofuran-2-one in a 100ml single-neck bottle, adding 15ml of tetrahydrofuran, adding 1ml of triethylamine after completely dissolving under magnetic stirring, introducing oxygen (with the ventilation amount of about 0.1 mol/H) at 35 ℃ for stirring and reacting, detecting no target product in a liquid phase after 4H, heating to 60 ℃ for reacting for 4H, and still not generating the target product.
Researches show that the method for preparing ketone by oxidation has certain requirements on the structure of the raw material, namely the method is only suitable for the raw material lactone with hydroxyl at the ortho position. In comparative examples 1 and 2, the reaction was not carried out when the preparation of the corresponding ketone was attempted using a lactone having no vicinal hydroxyl group and a lactone having a hydroxyl group at 4' as starting materials.
Claims (5)
1. A preparation method of 2, 2' -dihydroxy benzophenone compounds is characterized in that 5-alkyl-3- [ 5-alkyl-2-hydroxyphenyl ] benzofuran-2- (3H) -ketone is used as a raw material, the raw material is dissolved by a solvent, then an anhydrous catalyst is added, and oxygen or air is introduced for oxidation reaction; the reaction formula of the oxidation reaction is expressed as:
wherein the anhydrous catalyst is any one of lithium amide, diethylamine, triethylamine, sodium ethoxide, sodium carbonate and sodium bicarbonate; r1Is methyl, ethyl, isopropyl or tert-butyl, R2Is methyl, ethyl, isopropyl or tert-butyl; the solvent is any one of ethyl acetate, dichloromethane, tetrahydrofuran, methanol and dichloroethane.
2. The method according to claim 1, wherein the step of preparing the 2, 2' -dihydroxybenzophenone compound comprises the following steps: the addition amount of the solvent is 4-8 times of the mass of the raw materials.
3. The method according to claim 1, wherein the step of preparing the 2, 2' -dihydroxybenzophenone compound comprises the following steps: in the oxidation reaction, the reaction temperature is 15-45 ℃, and the ventilation quantity is 0.01-1 mol/h.
4. The process according to claim 3, wherein the reaction is carried out in the presence of a compound selected from the group consisting of: in the oxidation reaction, the reaction temperature is 25-35 ℃, and the ventilation quantity is 0.05-0.2 mol/h.
5. A process for preparing 2, 2' -dihydroxybenzophenone compounds according to any one of claims 1 to 4, characterized in that said oxidation reaction is followed by a purification step: and dissolving the oxidation reactant by using dichloromethane, cleaning the washing liquid to be below neutral, and evaporating the organic layer to dryness to obtain a finished product.
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