CN116239461A - Synthesis process of benzoic acid compound - Google Patents
Synthesis process of benzoic acid compound Download PDFInfo
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- CN116239461A CN116239461A CN202310007344.4A CN202310007344A CN116239461A CN 116239461 A CN116239461 A CN 116239461A CN 202310007344 A CN202310007344 A CN 202310007344A CN 116239461 A CN116239461 A CN 116239461A
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- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
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Abstract
The application relates to the technical field of organic synthesis, in particular to a synthesis process of a benzoic acid compound. The synthesis process of the benzoic acid compound comprises the following preparation steps: adding hydrogen peroxide into the mixed solution of the compound of the formula I and water, and adding povidone iodine at the temperature of-5-0 ℃ for oxidation reaction to obtain the compound of the formula II. Because the reaction system does not contain cobalt, manganese and other catalysts and contains heavy metals, the catalyst can be synthesized through one-step reaction. Therefore, the synthesis process improves the environmental protection performance of synthesizing the benzoic acid compound, and has the advantages of high efficiency, cleanness and wide applicability.
Description
Technical Field
The application relates to the technical field of organic synthesis, in particular to a synthesis process of a benzoic acid compound.
Background
Benzoic acid is an aromatic acid organic compound which can be used for synthesizing medicines, dyes, plasticizers, mordants, bactericides, fragrances and the like, so that the benzoic acid is also a common pharmaceutical and chemical intermediate.
At present, the synthesis method of benzoic acid is mainly prepared by adopting benzaldehyde, benzyl alcohol and toluene to perform oxidation reaction under the conditions of oxygen, cobalt, manganese and other catalysts. However, the catalyst such as cobalt and manganese contains heavy metals, is toxic and causes environmental pollution. Therefore, there is a need for an environment-friendly method for synthesizing benzoic acid.
Disclosure of Invention
In order to improve the environmental protection performance of synthesizing benzoic acid, the application provides a synthesis process of a benzoic acid compound.
The application provides a synthesis process of benzoic acid compounds, which adopts the following technical scheme:
a synthesis process of a benzoic acid compound comprises the following preparation steps:
adding hydrogen peroxide into a mixed solution of a compound shown in a formula I and water, and adding povidone iodine at the temperature of-5-0 ℃ to perform oxidation reaction to obtain a compound shown in a formula II;
the reaction formula of the preparation steps is as follows:
r is-H, -CH 3 ，-Br，-F，-Cl，-OCH 3 ，-NO 2 ，-CF 3 -one or more of i-PrO, -t-Bu.
By adopting the technical scheme, the benzyl position of benzyl alcohol is a more active reaction site, the application adopts water-soluble povidone iodine to slowly release iodine simple substance in a reaction system, the iodine simple substance reacts with hydrogen peroxide to form hydroxyl free radicals, the hydroxyl free radicals can react with the benzyl position of benzyl alcohol to obtain benzyl free radical intermediates, and the benzyl free radical intermediates further react under the oxidizing effect of the hydrogen peroxide, so that hydroxyl is introduced to form carboxylic acid functional groups, and the benzoic acid compound of the formula II is rapidly synthesized. Because the reaction system does not contain cobalt, manganese and other catalysts and contains heavy metals, the catalyst can be synthesized through one-step reaction. Therefore, the synthesis process of the benzoic acid compound has the advantages of high efficiency, cleanliness and wide applicability.
Preferably, the feeding amount of the compound shown in the formula I, hydrogen peroxide and povidone-iodine is 0.1mol (0.4-0.6 mol) and 0.05-0.3 mol.
Preferably, the dosage of the compound of formula I, hydrogen peroxide and povidone-iodine is 0.1mol:0.5mol:0.1mol.
By adopting the technical scheme, the raw materials are fed according to the feeding ratio, the yield and purity of the obtained benzoic acid compound are higher, and the residual unreacted raw materials are less.
Preferably, the reaction temperature of the oxidation reaction is 70-100 ℃ and the reaction time is 6-12h.
Preferably, the reaction temperature of the oxidation reaction is 90 ℃ and the reaction time is 6 hours.
By adopting the technical scheme, the raw materials are subjected to oxidation reaction at the temperature and in the time, so that the reaction efficiency of each raw material is higher, and the yield of the obtained benzoic acid compounds is improved.
Preferably, the synthesis process of the benzoic acid compound comprises the following preparation steps:
adding hydrogen peroxide into a mixed solution of a compound shown in a formula I and water, and adding povidone iodine at a temperature of between-5 and 0 ℃ for oxidation reaction, wherein the reaction temperature is between 70 and 100 ℃ and the reaction time is between 6 and 12 hours, so as to obtain a reaction solution containing the compound shown in a formula II;
the reaction solution is filtered by diatomite, and filtrate is collected and added with saturated sodium bicarbonate aqueous solution to obtain filtrate containing saturated sodium bicarbonate aqueous solution; extracting the filtrate containing saturated sodium bicarbonate water solution with an organic solvent, collecting a water phase, and regulating the pH value of the water phase to be 4-6 to obtain a water phase with the pH value of 4-6; and extracting, drying and concentrating the water phase with the pH value of 4-6 to obtain the compound of the formula II.
By adopting the technical scheme, the benzoic acid compound with higher purity can be obtained by adopting simple post-treatment modes such as filtration, extraction and the like, thereby being beneficial to improving the industrialized production efficiency of the benzoic acid compound.
Preferably, in the compound of formula I, R is-CH 3 ，-OCH 3 Any of the i-PrO.
By adopting the technical scheme, the benzyl alcohol comprises the substituent groups, the benzyl activity of the obtained benzyl alcohol compound is higher, the reaction of hydroxyl free radicals and benzyl positions can be promoted, and the synthesis efficiency and yield of the benzoic acid compound are improved.
Preferably, the compound of formula II is 3-methylbenzoic acid or 4-methoxybenzoic acid or 4-methylbenzoic acid or 4-isopropoxybenzoic acid.
By adopting the technical scheme, the yield of the product synthesized by the synthesis process is up to more than 80%, the purity is up to 95%, and the method is suitable for large-scale industrial production.
In summary, the present application has the following beneficial effects:
according to the method, benzyl alcohol compounds are used as reaction substrates, povidone iodine is used as a catalyst, the povidone iodine is promoted to react under the oxidation action of hydrogen peroxide to generate hydroxyl free radicals which can react with the benzyl alcohol compounds, and then the benzoic acid compounds are obtained under the further oxidation action of the hydrogen peroxide; therefore, the synthesis method of the benzoic acid compound can realize the direct conversion from the benzyl alcohol compound to the benzoic acid compound, and has the advantages of high efficiency, cleanness and wide applicability.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-1 in example 1 of the present application;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-2 in example 2 of the present application;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-3 in example 3 of the present application;
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of a compound of formula II-4 in example 4 of the present application;
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of the compound of formula II-5 in example 5 of the present application.
Detailed Description
The present application is described in further detail below with reference to the drawings and examples.
Examples
Example 1
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-1 (10.8 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: the reaction solution was filtered with celite and the filter cake was washed with ethyl acetate (300 mL), and then the filtrate was collected and saturated aqueous sodium bicarbonate solution (300 mL) was added to the filtrate to obtain a filtrate containing saturated aqueous sodium bicarbonate solution; extracting the filtrate containing saturated sodium bicarbonate aqueous solution with ethyl acetate three times (300 ml×3), collecting the aqueous phase and adjusting the pH of the aqueous phase to 2-3 (2 in this example), to obtain an aqueous phase with pH 2; extracting the aqueous phase with ethyl acetate at pH 2 three times (300 mL. Times.3), and collecting the organic phase; finally, the organic phase was dried and concentrated to leave no solvent, and then, referring to FIG. 1, the compound of formula II-1 (9.2 g, purity 95%, yield 75%, HNMR (400 MHz, DMSO-d 6): delta=12.97 (br. s, 1H), 7.94 (m, 2H), 7.60 (m, 1H), 7.48 (m, 2H))) was obtained.
Example 2
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-2 (12.3 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1 and referring to FIG. 2, a compound of formula II-2 (9.53 g, purity 95%, yield 70%, HNMR (400 MHz, DMSO-d 6): delta=12.81 (s, 1H), 7.80 (d, 1H,t = 8.0 Hz), 7.41(t, 1H, t = 8.0 Hz), 7.26 (t, 2H, t = 8.0 Hz), 2.49(s, 3H)）。
example 3
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-3 (18.7 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1 and with reference to FIG. 3, a compound of formula II-3 (13.0 g, purity 95%, yield 65%, HNMR (400 MHz, DMSO-d 6): delta=13.41 (s, 1H), 7.71 (m, 2H), 7.40 (m, 2H)) was obtained.
Example 4
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-4 (17.7 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1 and referring to FIG. 4, a compound of formula II-4 (11.46 g, purity 95%, yield 60%, HNMR (400 MHz, DMSO-d 6): delta=13.63 (s, 1H), 7.80 (m, 3H)) was obtained.
Example 5
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-5 (12.6 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1 and referring to FIG. 5, a compound of formula II-5 (9.8 g, purity 95%, yield 70%, HNMR (400 MHz, DMSO-d 6): delta=13.28 (s, 1H), 7.76 (d, 1H,t = 8.0 Hz), 7.62(d, 1H, t = 8.0 Hz), 7.53 (t, 1H, t = 8.0 Hz), 7.44 (t, 1H, t = 8.0 Hz)）。
example 6
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-6 (12.3 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-6 (10.9 g, purity 95%, yield 80%, HNMR (400 MHz, DMSO-d 6): δ=12.84 (s, 1H), 7.72 (d, 2H,t = 8.0 Hz), 7.36(m, 2H),2.32 (s, 3H)）。
example 7
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-7 (17.6 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-7 (11.8 g,purity 95%, yield 62%, HNMR (400 MHz, DMSO-d 6): δ=13.50 (s, 1H), 8.24 (d, 1H,t = 8.0 Hz), 8.18(s, 1H), 8.01 (d, 1H, t = 4.0 Hz), 7.77 (t, 1H, t = 8.0 Hz)）。
example 8
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-8 (12.6 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-8 (9.52 g, purity 95%, yield 68%, HNMR (400 MHz, DMSO-d 6): δ=13.00 (s, 1H), 7.98 (t, 2H,t = 8.0 Hz), 7.29(d, 2H, t= 8.0 Hz)）。
example 9
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-9 (12.3 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-9 (11.1 g, purity 95%, yield 82%, HNMR (400 MHz, DMSO-d 6): δ=12.79 (s, 1H), 7.82 (t, 2H,t = 8.0 Hz), 7.20(t, 2H, t= 8.0 Hz), 2.28(s, 3H)）。
example 10
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-10 (13.8 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-10 (12.9 g, purity 95%, yield 85%, HNMR (400 MHz, DMSO-d 6): δ=12.62 (s, 1H), 7.87 (d, 2H,t = 8.0 Hz), 7.99(d, 2H, t= 8.0 Hz), 3.79(s, 3H) ）。
example 11
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-11 (17.6 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-11 (12.3 g, purity 95%, yield 65%, HNMR (400 MHz, DMSO-d 6): δ=13.48 (s, 1H), 8.11 (d, 2H,t = 8.0 Hz), 7.85(d, 2H, t= 8.0 Hz)）。
example 12
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-12 (16.4 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-12 (13.9 g, purity 95%, yield 78%, HNMR (400 MHz, DMSO-d 6): δ=12.80 (s, 1H), 7.84 (d, 2H,t = 8.0 Hz), 7.47(d, 2H, t= 8.0 Hz), 1.26(s, 9H)）。
example 13
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-13 (15.3 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-13 (9.2 g, purity 95%, yield 55%, HNMR (400 MHz, DMSO-d 6): δ=13.66 (s, 1H), 8.28 (t, 2H,t = 8.0 Hz), 8.13(t, 2H, t= 8.0 Hz)）。
example 14
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
s1, feeding: the compound of formula I-14 (16.6 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-14 (14.4 g, purity 95%, yield 80%, HNMR (400 MHz, DMSO-d 6): δ=12.58 (s, 1H), 7.84 (d, 2H,t = 8.0 Hz), 6.96(d, 2H, t= 8.0 Hz), 4.71(m, 1H), 1.25(d, 6H, t = 4.0 Hz ）。
example 15
A benzoic acid compound, different from example 1 in the synthesis process of the benzoic acid compound, comprising the steps of:
s1, feeding: the compound of formula I-1 (10.8 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (45.3 g,0.4 mol) is added into the mixed solution, povidone iodine (18.2 g,0.05 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: as in example 1, a compound of formula II-1 (8.0 g, purity 95%, yield 65.2%, HNMR (400 MHz, CDCl) 3 ): δ = 12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H)））。
Example 16
A benzoic acid compound, different from example 1 in the synthesis process of the benzoic acid compound, comprising the steps of:
s1, feeding: the compound of formula I-1 (10.8 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (68.0 g,0.6 mol) is added into the mixed solution, povidone iodine (109.5 g,0.3 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 6 hours at the temperature of 90 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-1 (9.2 g, purity 95%, yield 75%, HNMR (400 MHz, CDCl 3): δ=12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H))) was obtained.
Example 17
A benzoic acid compound, different from example 1 in the synthesis process of the benzoic acid compound, comprising the steps of:
s1, feeding: the compound of formula I-1 (10.8 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 12h at the temperature of 70 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of the formula II-1 (7.5 g, purity 95%, yield 61.1%, HNMR (400 MHz, CDCl 3): δ=12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H))) was obtained.
Example 18
A benzoic acid compound, different from example 1 in the synthesis process of the benzoic acid compound, comprising the steps of:
s1, feeding: the compound of formula I-1 (10.8 g,0.1 mol) was added to deionized water (200 mL) to give a mixture; 30% hydrogen peroxide (56.7 g,0.5 mol) is added into the mixed solution, povidone iodine (36.5 g,0.1 mol) is added at the temperature of-5-0 ℃, then oxidation reaction is carried out for 8 hours at the temperature of 100 ℃, and TLC (PE: EA=1:1, product Rf=0.2) monitors that the compound of the formula I is completely reacted, so as to obtain a reaction solution;
s2, post-treatment: in the same manner as in example 1, a compound of formula II-1 (9.0 g, purity 95%, yield 73.4%, HNMR (400 MHz, CDCl 3): δ=12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H))) was obtained.
Comparative example
Comparative example 1
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
cobalt chloride hexahydrate (0.1 g) was added to toluene (30 g) to obtain a mixed solution; the mixture was added to benzaldehyde (75 g), then 0.3L/min of oxygen was introduced, and the mixture was stirred at 75-80℃for reaction for 6 hours to give a reaction solution. The reaction solution was filtered and the filter cake was washed 2 times with clear water, then the filter cake was dried at 65℃for 5 hours, the filter cake was added to water (water and filter cake were mixed in a weight ratio of 10:1), heated to 100℃until the filter cake was dissolved, then naturally cooled to room temperature (20-25 ℃) and white crystals were precipitated, filtered, and the white crystals were collected to give a compound of formula II-1 (43.65 g, 93% purity, 51.2% yield, HNMR (400 MHz, DMSO-d 6): δ=12.97 (br. s, 1H), 7.94 (m, 2H), 7.60 (m, 1H), 7.48 (m, 2H))).
Comparative example 2
A benzoic acid compound has a specific structural formula:
the reaction equation of the synthesis process of the benzoic acid compound is as follows:
the synthesis process of the benzoic acid compound comprises the following steps:
cobalt chloride hexahydrate (0.1 g) and tween-8 (37.5 mg) as an emulsifier were added to water (50 g) to obtain a mixed solution; the mixture was added to benzaldehyde (75 g), then 0.3L/min of oxygen was introduced, and the mixture was stirred at 75-80℃for reaction for 6 hours to give a reaction solution. The reaction solution was filtered and the filter cake was washed 2 times with clear water, then the filter cake was dried at 65℃for 5 hours, the filter cake was added to water (water and filter cake were mixed in a weight ratio of 10:1), heated to 100℃until the filter cake was dissolved, then naturally cooled to room temperature (20-25 ℃) and white crystals were precipitated, filtered, and the white crystals were collected to give a compound of formula II-1 (57.6 g, 92% purity, 68.1% yield, HNMR (400 MHz, DMSO-d 6): δ=12.97 (br. s, 1H), 7.94 (m, 2H), 7.60 (m, 1H), 7.48 (m, 2H))).
From analysis of example 1, comparative example 1 and comparative example 2, it is apparent that the products obtained in example 1, comparative example 1 and comparative example 2 are benzoic acid, wherein the purity and yield of benzoic acid are shown in the following table:
as can be seen from the analysis described above, the benzoic acid obtained in example 1 was higher in purity and yield than those obtained in comparative examples 1 and 2. Therefore, the benzoic acid synthesized by adopting the synthesis process of the benzoic acid compound can improve the purity and the yield of the benzoic acid. Meanwhile, hydrogen peroxide, water and povidone iodine are all green pollution-free raw materials in the synthesis process. However, in the synthesis process of comparative example 1 and comparative example 2, toxic cobalt chloride hexahydrate is used, and in the synthesis process of comparative example 1, toluene, which is an organic solvent, is also used, which causes environmental pollution. Therefore, the synthesis process of the benzoic acid compound is more environment-friendly and cleaner. Moreover, the synthesis process of the benzoic acid compound is simple and convenient to operate, the material is simple, oxygen is also required to be introduced into the comparative examples 1 and 2, and the dosage of the oxygen is controlled, so that the synthesis process of the benzoic acid compound is more efficient and has wider applicability.
The present embodiment is merely illustrative of the present application and is not intended to be limiting, and those skilled in the art, after having read the present specification, may make modifications to the present embodiment without creative contribution as required, but is protected by patent laws within the scope of the claims of the present application.
Claims (8)
1. The synthesis process of the benzoic acid compound is characterized by comprising the following preparation steps:
adding hydrogen peroxide into a mixed solution of a compound shown in a formula I and water, and adding povidone iodine at the temperature of-5-0 ℃ to perform oxidation reaction to obtain a compound shown in a formula II;
the reaction formula of the preparation steps is as follows:
r is one or more of-H, -CH3, -Br, -F, -Cl, -OCH3, -NO2, -CF3, -i-PrO, -t-Bu.
2. The process for synthesizing the benzoic acid compound according to claim 1, wherein the feeding amount of the compound of formula I, hydrogen peroxide and povidone-iodine is 1mol (4-6 mol) (0.5-3 mol).
3. The process for synthesizing the benzoic acid compound according to claim 2, wherein the amounts of the compound of formula i, hydrogen peroxide and povidone-iodine added are 1mol:5mol:1.0mol.
4. The process for synthesizing benzoic acid compounds according to claim 1 wherein the reaction temperature of the oxidation reaction is 70-100 ℃ and the reaction time is 6-12h.
5. The process for synthesizing benzoic acid compounds according to claim 4 wherein the reaction temperature of the oxidation reaction is 90 ℃ and the reaction time is 6 hours.
6. The process for synthesizing the benzoic acid compound according to claim 1, wherein the process for synthesizing the benzoic acid compound comprises the following preparation steps:
adding hydrogen peroxide into a mixed solution of a compound shown in a formula I and water, and adding povidone iodine at a temperature of between-5 and 0 ℃ for oxidation reaction, wherein the reaction temperature is between 70 and 100 ℃ and the reaction time is between 6 and 12 hours, so as to obtain a reaction solution containing the compound shown in a formula II;
the reaction solution is filtered by diatomite, and filtrate is collected and added with saturated sodium bicarbonate aqueous solution to obtain filtrate containing saturated sodium bicarbonate aqueous solution; extracting the filtrate containing saturated sodium bicarbonate water solution with an organic solvent, collecting a water phase, and regulating the pH value of the water phase to be 4-6 to obtain a water phase with the pH value of 4-6; and extracting, drying and concentrating the water phase with the pH value of 4-6 to obtain the compound of the formula II.
7. The process according to claim 1, wherein R is-CH in the compound of formula I 3 ，-OCH 3 Any of the i-PrO.
8. The process for the synthesis of benzoic acid compounds according to claim 1 wherein the compound of formula ii is 3-methylbenzoic acid or 4-methoxybenzoic acid or 4-methylbenzoic acid or 4-isopropoxybenzoic acid.
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