A process for the synthesis of benzoic acid compounds

Abstract

The application relates to the technical field of organic synthesis, in particular to a synthesis process of benzoic acid compounds. The synthesis process of the benzoic acid compounds comprises the following preparation steps: hydrogen peroxide is added into a mixed solution of a compound of formula I and water, polyvidone iodine is added at-5-0 DEG C to carry out an oxidation reaction, and a compound of formula II is obtained. Since the reaction system of the application does not contain catalysts containing heavy metals such as cobalt and manganese, and the synthesis can be completed through one step, the synthesis process of the application improves the environmental protection performance of the synthesized benzoic acid compounds, and has the advantages of high efficiency, cleanness and wide applicability.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of organic synthesis, in particular to a synthesis process of benzoic acid compounds. BACKGROUND

[0002] Benzoic acid is an aromatic acid organic compound, which can be used for synthesizing drugs, dyes, plasticizers, mordants, fungicides and spices, and therefore is a common pharmaceutical and chemical intermediate.

[0003] At present, the synthesis method of benzoic acid mainly adopts benzaldehyde, benzyl alcohol and toluene to be subjected to an oxidation reaction under the condition of oxygen and a catalyst such as cobalt and manganese to obtain the benzoic acid. However, the catalysts such as cobalt and manganese contain heavy metals, which are not only toxic but also pollute the environment. Therefore, an environmentally friendly synthesis method of benzoic acid is urgently needed at present. SUMMARY

[0004] In order to improve the environmental performance of the synthesis of benzoic acid, the application provides a synthesis process of benzoic acid compounds.

[0005] The application provides a synthesis process of benzoic acid compounds, which adopts the following technical scheme:

[0006] The synthesis process of the benzoic acid compounds comprises the following preparation steps:

[0007] The hydrogen peroxide is added into a mixed solution of the compound of formula I and water, and the povidone iodine is added at-5-0 DEG C to perform an oxidation reaction, so as to obtain the compound of formula II.

[0008] The reaction formula of the above preparation step is as follows:

[0009] ;

[0010] R is one or more of -H, -CH3, -Br, -F, -Cl, -OCH3, -NO2, -CF3, -i-PrO, -t-Bu.

[0011] By adopting the above technical scheme, the benzyl position of benzyl alcohol is a relatively active reaction site, the water-soluble povidone iodine is adopted in the reaction system to slowly release the iodine element, and the iodine element reacts with the hydrogen peroxide to form a hydroxyl radical, the hydroxyl radical can react with the benzyl position of the benzyl alcohol to obtain a benzyl radical intermediate, and the benzyl radical intermediate is further reacted under the oxidation of the hydrogen peroxide, so as to introduce a hydroxyl group to form a carboxylic acid functional group, and the benzoic acid compound of formula II is rapidly synthesized. Since the reaction system of the application does not contain the catalysts such as cobalt and manganese containing heavy metals, and the synthesis can be completed in one step, the synthesis process of the benzoic acid compound of the application has the advantages of high efficiency, cleanness and wide applicability.

[0012] Preferably, the feeding amount of the compound of formula I, hydrogen peroxide and povidone iodine is 0.1 mol:(0.4-0.6) mol:(0.05-0.3) mol.

[0013] Preferably, the feeding amount of the compound of formula I, hydrogen peroxide and povidone iodine is 0.1 mol:0.5 mol:0.1 mol.

[0014] By using the above technical solution, the raw materials are fed according to the above feeding ratio, and the yield and purity of the obtained benzoic acid compound are high, and the residual unreacted raw materials are less.

[0015] Preferably, the reaction temperature of the oxidation reaction is 70-100°C, and the reaction time is 6-12h.

[0016] Preferably, the reaction temperature of the oxidation reaction is 90°C, and the reaction time is 6h.

[0017] By using the above technical solution, the raw materials are fed according to the above feeding ratio, and the yield and purity of the obtained benzoic acid compound are high, and the residual unreacted raw materials are less.

[0018] Preferably, the synthesis process of the benzoic acid compound comprises the following preparation steps:

[0019] The hydrogen peroxide is added to the mixture of the compound of formula I and water, and the povidone iodine is added at -5-0°C to perform the oxidation reaction, wherein the reaction temperature is 70-100°C, and the reaction time is 6-12h, to obtain a reaction liquid containing the compound of formula II;

[0020] The reaction liquid is first filtered with diatomite, the filtrate is collected, and saturated sodium bicarbonate aqueous solution is added to the filtrate to obtain a filtrate containing saturated sodium bicarbonate aqueous solution; then the filtrate containing saturated sodium bicarbonate aqueous solution is extracted with an organic solvent, the aqueous phase is collected, and the pH value of the aqueous phase is adjusted to 4-6 to obtain an aqueous phase with a pH value of 4-6; and after the aqueous phase with a pH value of 4-6 is extracted, dried and concentrated, the compound of formula II is obtained.

[0021] By using the above technical solution, a simple post-treatment method such as filtration and extraction can be used to obtain a benzoic acid compound with high purity, which is beneficial to improve the industrial production efficiency of the benzoic acid compound.

[0022] Preferably, in the compound of formula I, R is any one of -CH3, -OCH3 and -i-PrO.

[0023] By using the above technical solution, the benzyl position of the obtained benzylic alcohol compound has high reactivity, which can promote the reaction of hydroxyl radicals with the benzyl position, and is beneficial to improve the synthesis efficiency and yield of the benzoic acid compound.

[0024] Preferably, the compound of formula II is 3-methylbenzoic acid or 4-methoxybenzoic acid or 4-methylbenzoic acid or 4-isopropoxybenzoic acid.

[0025] By adopting the technical scheme, the above product synthesized by the synthesis process of the application has a yield of more than 80% and a purity of up to 95%, and is suitable for large-scale industrial production.

[0026] In summary, the application has the following beneficial effects:

[0027] The application uses benzylic alcohol compounds as reaction substrates, polyvinyl iodine as a catalyst, and hydrogen peroxide for oxidation, which promotes the reaction of polyvinyl iodine to generate hydroxyl radicals that can react with benzylic alcohol compounds, and then further oxidation by hydrogen peroxide to obtain benzoic acid compounds. Therefore, the synthesis method of the benzoic acid compounds of the application can realize the direct conversion of benzylic alcohol compounds to benzoic acid compounds, and has the advantages of high efficiency, cleanliness and wide applicability. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is the nuclear magnetic resonance hydrogen spectrum of the compound of formula II-1 in Example 1 of the application;

[0029] Figure 2 is the nuclear magnetic resonance hydrogen spectrum of the compound of formula II-2 in Example 2 of the application;

[0030] Figure 3 is the nuclear magnetic resonance hydrogen spectrum of the compound of formula II-3 in Example 3 of the application;

[0031] Figure 4 is the nuclear magnetic resonance hydrogen spectrum of the compound of formula II-4 in Example 4 of the application;

[0032] Figure 5 is the nuclear magnetic resonance hydrogen spectrum of the compound of formula II-5 in Example 5 of the application. DETAILED DESCRIPTION

[0033] The application will be further described in detail below in combination with the drawings and examples. EMBODIMENT

[0034] Example 1

[0035] A benzoic acid compound, the specific structural formula of which is:

[0036] Formula II-1;

[0037] The reaction equation of the synthesis process of the above benzoic acid compound is as follows:

[0038] .

[0039] The synthesis process of the benzoic acid compound comprises the following steps:

[0040] S1 feeding: the compound of formula I-1 (10.8 g, 0.1 mol) is added into deionized water (200 mL) to obtain a mixed solution; 30% hydrogen peroxide (56.7 g, 0.5 mol) is added into the mixed solution, and povidone iodine (36.5 g, 0.1 mol) is added at-5-0°C, and then the oxidation reaction is carried out at 90°C for 6h, and TLC (PE:EA=1:1, product Rf=0.2) monitoring shows that the compound of formula I is completely reacted to obtain a reaction solution;

[0041] S2 post-treatment: the reaction solution is first filtered with diatomite, and the filter cake is washed with ethyl acetate (300 mL), then the filtrate is collected, and saturated sodium bicarbonate aqueous solution (300 mL) is added into the filtrate to obtain a filtrate containing saturated sodium bicarbonate aqueous solution; then the filtrate containing saturated sodium bicarbonate aqueous solution is extracted with ethyl acetate three times (300 mL*3), the aqueous phase is collected and the pH value of the aqueous phase is adjusted to 2-3 (2 in this embodiment), to obtain an aqueous phase with a pH value of 2; the aqueous phase with a pH value of 2 is extracted with ethyl acetate three times (300 mL*3), and the organic phase is collected; finally, the organic phase is dried, concentrated to no solvent residue, and then Figure 1 , to obtain the compound of formula II-1 (9.2 g, purity 95%, yield 75%, HNMR (400 MHz, DMSO-d6): δ = 12.97 (br. s, 1H), 7.94 (m, 2H), 7.60 (m, 1H), 7.48 (m, 2H))).

[0042] Example 2

[0043] A benzoic acid compound, and the specific structural formula is:

[0044] Formula II-2;

[0045] The synthesis process of the benzoic acid compound, and the reaction equation is as follows:

[0046] .

[0047] The synthesis process of the benzoic acid compound comprises the following steps:

[0048] S1 feeding: the compound of formula I-2 (12.3 g, 0.1 mol) was added into deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added into the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0049] S2 post-treatment: the same as example 1, refer to Figure 2 , to obtain the compound of formula II-2 (9.53 g, purity 95%, yield 70%, HNMR (400 MHz, DMSO-d6): δ = 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)).

[0050] Example 3

[0051] A benzoic acid compound, the specific structural formula of which is:

[0052] Formula II-3;

[0053] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0054] .

[0055] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0056] S1 feeding: the compound of formula I-3 (18.7 g, 0.1 mol) was added into deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added into the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0057] S2 post-treatment: the same as example 1, refer to Figure 3, to obtain the compound of formula II-3 (13.0 g, purity 95%, yield 65%, HNMR (400 MHz, DMSO-d6): δ = 13.41 (s, 1 H), 7.71 (m, 2H), 7.40 (m, 2H)).

[0058] Example 4

[0059] A benzoic acid compound, the specific structural formula of which is:

[0060] Formula II-4;

[0061] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0062] .

[0063] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0064] S1 feeding: the compound of formula I-4 (17.7 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixed solution; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixed solution, and povidone iodine (36.5 g, 0.1 mol) was added at-5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0065] S2 post-treatment: the same as example 1, refer to Figure 4 , to obtain the compound of formula II-4 (11.46 g, purity 95%, yield 60%, HNMR (400 MHz, DMSO-d6): δ = 13.63 (s, 1 H), 7.80 (m, 3H)).

[0066] Example 5

[0067] A benzoic acid compound, the specific structural formula of which is:

[0068] Formula II-5;

[0069] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0070] .

[0071] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0072] S1 feeding: the compound of formula I-5 (12.6 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, followed by oxidation reaction at 90°C for 6 h. TLC (PE:EA = 1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0073] S2 post-treatment: the same as example 1, refer to Figure 5 , to obtain the compound of formula II-5 (9.8 g, purity 95%, yield 70%, HNMR (400 MHz, DMSO-d6): δ = 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) ).

[0074] Example 6

[0075] A benzoic acid compound, the specific structural formula of which is:

[0076] Formula II-6;

[0077] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0078] .

[0079] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0080] S1 feeding: the compound of formula I-5 (12.6 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, followed by oxidation reaction at 90°C for 6 h. TLC (PE:EA = 1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0081] S2 post-processing: same as example 1, to obtain the compound of formula II-6 (10.9g, purity 95%, yield 80%, HNMR (400 MHz, DMSO-d6): δ = 12.84 (s, 1H), 7.72 (d, 2H, t = 8.0 Hz), 7.36 (m, 2H), 2.32 (s, 3H)).

[0082] Example 7

[0083] A benzoic acid compound, the specific structural formula is:

[0084] Formula II-7;

[0085] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0086] .

[0087] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0088] S1 feeding: the compound of formula I-7 (17.6g, 0.1mol) is added to deionized water (200mL) to obtain a mixed solution; 30% hydrogen peroxide (56.7g, 0.5mol) is added to the mixed solution, and povidone iodine (36.5g, 0.1mol) is added at-5-0℃, and then the oxidation reaction is carried out at 90℃ for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring the compound of formula I is completely reacted, to obtain a reaction solution;

[0089] S2 post-processing: same as example 1, to obtain the compound of formula II-7 (11.8g, purity 95%, yield 62%, HNMR (400 MHz, DMSO-d6): 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).

[0090] Example 8

[0091] A benzoic acid compound, the specific structural formula is:

[0092] Formula II-8;

[0093] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0094] .

[0095] The synthesis process of the benzoic acid compound comprises the following steps:

[0096] S1 feeding: the compound of formula I-8 (12.6 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA = 1:1, product Rf=0.2) monitoring that the compound of formula I was completely reacted to obtain a reaction solution;

[0097] S2 post-treatment: the same as example 1, to obtain the compound of formula II-8 (9.52 g, purity 95%, yield 68%, HNMR (400 MHz, DMSO-d6): δ = 13.00 (s, 1 H), 7.98 (t, 2H, t = 8.0 Hz), 7.29 (d, 2H, t = 8.0 Hz) ).

[0098] Example 9

[0099] A benzoic acid compound, and the specific structural formula is:

[0100] Formula II-9;

[0101] The synthesis process of the benzoic acid compound, and the reaction equation is as follows:

[0102] .

[0103] The synthesis process of the benzoic acid compound comprises the following steps:

[0104] S1 feeding: the compound of formula I-9 (12.3 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA = 1:1, product Rf=0.2) monitoring that the compound of formula I was completely reacted to obtain a reaction solution;

[0105] S2 Post-processing: Same as in Example 1, yielding compound of formula II-9 (11.1 g, purity 95%, yield 82%, HNMR (400 MHz, DMSO-d6): δ = 12.79 (s, 1 H), 7.82 (t, 2 H, 1 H), δ = 12.79 (s, 1 H), δ = 7.82 (t, 2 H, 1 H). t = 8.0 Hz), 7.20(t, 2H, t = 8.0 Hz), 2.28(s, 3H)).

[0106] Example 10

[0107] A benzoic acid compound, the specific structural formula of which is:

[0108] Formula II-10;

[0109] The reaction equations for the synthesis of the above-mentioned benzoic acid compounds are as follows:

[0110] .

[0111] The synthesis process of the above-mentioned benzoic acid compounds includes the following steps:

[0112] S1 Feeding: Add 13.8 g (0.1 mol) of the compound of formula I-10 to deionized water (200 mL) to obtain a mixture; add 30% hydrogen peroxide (56.7 g, 0.5 mol) to the mixture, and add povidone-iodine (36.5 g, 0.1 mol) at -5 to 0 °C, and then carry out an oxidation reaction at 90 °C for 6 h. TLC (PE:EA=1:1, product Rf=0.2) shows that the compound of formula I has reacted completely, and the reaction solution is obtained.

[0113] S2 Post-processing: Same as in Example 1, yielding compound of formula II-10 (12.9 g, purity 95%, yield 85%, HNMR (400 MHz, DMSO-d6): δ = 12.62 (s, 1 H), 7.87 (d, 2 H, 1 H), δ = 12.62 (s, 1 H), δ = 7.87 (d, 2 H, 1 H). t = 8.0 Hz), 7.99(d, 2H, t = 8.0 Hz), 3.79(s, 3H) ).

[0114] Example 11

[0115] A benzoic acid compound, the specific structural formula of which is:

[0116] Formula II-11;

[0117] The reaction equations for the synthesis of the above-mentioned benzoic acid compounds are as follows:

[0118] .

[0119] The synthesis process of the benzoic acid compound comprises the following steps:

[0120] S1 feeding: the compound of formula I-11 (17.6 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, and TLC (PE:EA = 1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0121] S2 post-treatment: the same as example 1, to obtain the compound of formula II-11 (12.3 g, purity 95%, yield 65%, HNMR (400 MHz, DMSO-d6): δ = 13.48 (s, 1 H), 8.11 (d, 2H, t = 8.0 Hz), 7.85 (d, 2H, t = 8.0 Hz) ).

[0122] Example 12

[0123] A benzoic acid compound, the specific structural formula of which is:

[0124] Formula II-12;

[0125] The synthesis process of the benzoic acid compound, the reaction equation of which is as follows:

[0126] .

[0127] The synthesis process of the benzoic acid compound comprises the following steps:

[0128] S1 feeding: the compound of formula I-11 (17.6 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, and TLC (PE:EA = 1:1, product Rf=0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0129] S2 post-processing: same as example 1, to obtain the compound of formula II-12 (13.9g, purity 95%, yield 78%, HNMR (400 MHz, DMSO-d6): δ = 12.80 (s, 1 H), 7.84 (d, 2H, t = 8.0 Hz), 7.47 (d, 2H, t = 8.0 Hz), 1.26 (s, 9H))。

[0130] Example 13

[0131] A benzoic acid compound, the specific structural formula is:

[0132] Formula II-13;

[0133] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0134] .

[0135] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0136] S1 feeding: the compound of formula I-13 (15.3g, 0.1mol) is added to deionized water (200mL) to obtain a mixed solution; 30% hydrogen peroxide (56.7g, 0.5mol) is added to the mixed solution, and povidone iodine (36.5g, 0.1mol) is added at-5-0℃, and then the oxidation reaction is carried out at 90℃ for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring that the compound of formula I is completely reacted to obtain a reaction solution;

[0137] S2 post-processing: same as example 1, to obtain the compound of formula II-13 (9.2g, purity 95%, yield 55%, HNMR (400 MHz, DMSO-d6): δ = 13.66 (s, 1 H), 8.28 (t, 2H, t = 8.0 Hz), 8.13 (t, 2H, t = 8.0 Hz))。

[0138] Example 14

[0139] A benzoic acid compound, the specific structural formula is:

[0140] Formula II-14;

[0141] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0142] .

[0143] The synthesis process of the benzoic acid compound comprises the following steps:

[0144] S1 feeding: the compound of formula I-14 (16.6 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixed solution; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added to the mixed solution, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring that the compound of formula I was completely reacted to obtain a reaction solution;

[0145] S2 post-treatment: the same as example 1, to obtain the compound of formula II-14 (14.4 g, purity 95%, yield 80%, HNMR (400 MHz, DMSO-d6): 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).

[0146] Example 15

[0147] A benzoic acid compound, which is different from example 1, the synthesis process of the benzoic acid compound comprises the following steps:

[0148] S1 feeding: the compound of formula I-1 (10.8 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixed solution; 30% hydrogen peroxide (45.3 g, 0.4 mol) was added to the mixed solution, and povidone iodine (18.2 g, 0.05 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring that the compound of formula I was completely reacted to obtain a reaction solution;

[0149] S2 post-treatment: the same as example 1, to obtain the compound of formula II-1 (8.0 g, purity 95%, yield 65.2%, HNMR (400 MHz, CDCl3): δ = 12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H)).

[0150] Example 16

[0151] A benzoic acid compound, different from example 1, the synthesis process of the benzoic acid compound comprises the following steps:

[0152] S1 feeding: the compound of formula I-1 (10.8 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (68.0 g, 0.6 mol) was added to the mixture, and povidone iodine (109.5 g, 0.3 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring the compound of formula I was completely reacted to obtain a reaction liquid;

[0153] S2 post-processing: the same as example 1, to obtain the compound of formula II-1 (9.2 g, purity 95%, yield 75%, HNMR(400 MHz, CDCl3): δ = 12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H) )).

[0154] Example 17

[0155] A benzoic acid compound, different from example 1, the synthesis process of the benzoic acid compound comprises the following steps:

[0156] S1 feeding: the compound of formula I-1 (10.8 g, 0.1 mol) was added to deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (68.0 g, 0.6 mol) was added to the mixture, and povidone iodine (109.5 g, 0.3 mol) was added at -5-0°C, and then the oxidation reaction was carried out at 90°C for 6h, TLC (PE:EA=1:1, product Rf=0.2) monitoring the compound of formula I was completely reacted to obtain a reaction liquid;

[0157] S2 post-processing: the same as example 1, to obtain the compound of formula II-1 (9.2 g, purity 95%, yield 75%, HNMR(400 MHz, CDCl3): δ = 12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H) )).

[0158] Example 18

[0159] A benzoic acid compound, different from example 1, the synthesis process of the benzoic acid compound comprises the following steps:

[0160] S1 feeding: the compound of formula I-1 (10.8 g, 0.1 mol) was added into deionized water (200 mL) to obtain a mixture; 30% hydrogen peroxide (56.7 g, 0.5 mol) was added into the mixture, and povidone iodine (36.5 g, 0.1 mol) was added at -5-0 °C, and then the oxidation reaction was carried out at 100 °C for 8 h, and TLC (PE:EA = 1:1, product Rf = 0.2) monitoring showed that the compound of formula I was completely reacted to obtain a reaction solution;

[0161] S2 post-treatment: the same as example 1 to obtain the compound of formula II-1 (9.0 g, purity 95%, yield 73.4%, HNMR (400 MHz, CDCl3): δ = 12.08 (br. s, 1H), 8.16-8.13 (m, 2H), 7.65-7.61 (m, 1H), 7.52-7.47 (m, 2H))。

[0162] Comparative example

[0163] Comparative example 1

[0164] A benzoic acid compound, and its specific structural formula is:

[0165] Formula II-1;

[0166] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0167] .

[0168] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0169] Cobalt chloride hexahydrate (0.1 g) was added into toluene (30 g) to obtain a mixture; the mixture was added into benzaldehyde (75 g), then 0.3 L / min oxygen was introduced, and the reaction was stirred at 75-80 °C for 6 h to obtain a reaction solution. The reaction solution was filtered, and the filter cake was washed with water twice, and then the filter cake was dried at 65 °C for 5 h, the filter cake was added into water (water and filter cake were mixed according to a weight ratio of 10:1), heated to 100 °C until the filter cake was dissolved, and then naturally cooled to room temperature (20-25 °C), white crystals were precipitated, filtered, and the white crystals were collected to obtain the compound of formula II-1 (43.65 g, purity 93%, yield 51.2%, HNMR (400 MHz, DMSO-d6): δ = 12.97 (br. s, 1H), 7.94 (m, 2H), 7.60 (m, 1H), 7.48 (m, 2H))。

[0170] Comparative example 2

[0171] A benzoic acid compound, and its specific structural formula is:

[0172] Formula II-1;

[0173] The reaction equation of the synthesis process of the above-mentioned benzoic acid compound is as follows:

[0174] .

[0175] The synthesis process of the above-mentioned benzoic acid compound comprises the following steps:

[0176] Cobalt chloride hexahydrate (0.1 g) and emulsifier Tween-8 (37.5 mg) were added to water (50 g) to obtain a mixed solution; the mixed solution was added to benzaldehyde (75 g), then 0.3 L / min oxygen was introduced, and the reaction was stirred at 75-80°C for 6 h to obtain a reaction liquid. The reaction liquid was filtered, and the filter cake was washed with water twice, then the filter cake was dried at 65°C for 5 h, the filter cake was added to water (water and filter cake were mixed at a weight ratio of 10:1), heated to 100°C until the filter cake was dissolved, then naturally cooled to room temperature (20-25°C), white crystals were precipitated, filtered, and the white crystals were collected to obtain the compound of formula II-1 (57.6 g, purity 92%, yield 68.1%, HNMR (400 MHz, DMSO-d6): δ = 12.97 (br. s, 1H), 7.94 (m, 2H), 7.60 (m, 1H), 7.48 (m, 2H)).

[0177] Through analysis of Example 1, Comparative Example 1 and Comparative Example 2, it can be seen that the products obtained in Example 1, Comparative Example 1 and Comparative Example 2 are benzoic acid, and the purity and yield of the benzoic acid are shown in the following table:

[0178]

[0179] Analysis of the above results shows that the purity and yield of benzoic acid obtained in Example 1 are higher than those in Comparative Examples 1 and 2. This indicates that the synthesis process of benzoic acid compounds according to this application can improve the purity and yield of benzoic acid. Furthermore, the hydrogen peroxide, water, and povidone-iodine used in the synthesis process of this application are all green and pollution-free raw materials. However, the synthesis processes of Comparative Examples 1 and 2 both used toxic cobalt chloride hexahydrate, and Comparative Example 1 also used the organic solvent toluene, which would pollute the environment. Therefore, the synthesis process of benzoic acid compounds according to this application is more environmentally friendly and cleaner. Moreover, the synthesis process of benzoic acid compounds according to this application is simple to operate and requires simple feeding. Comparative Examples 1 and 2 require the introduction of oxygen and control of the oxygen dosage. Therefore, the synthesis process of benzoic acid compounds according to this application is more efficient and has wider applicability.

[0180] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A process for the synthesis of benzoic acid compounds, characterized in that, The preparation process comprises the following steps: The compound of formula I and water are mixed, and hydrogen peroxide is added, and povidone iodine is added at -5-0 DEG C to perform an oxidation reaction to obtain a compound of formula II; The reaction formula of the above preparation process is as follows: R is one or more of -H, -CH3, -Br, -F, -Cl, -OCH3, -NO2, -CF3, -i-PrO, and -t-Bu; The feeding amount of the compound of formula I, hydrogen peroxide, and povidone iodine is 1 mol:(4-6) mol:(0.5-3) mol; The reaction temperature of the oxidation reaction is 70-100 DEG C, and the reaction time is 6-12 h.

2. The process for synthesis of benzoic acid compound as claimed in claim 1 wherein, The feeding amount of the compound of formula I, hydrogen peroxide, and povidone iodine is 1 mol:5 mol:1.0 mol.

3. The process for synthesis of benzoic acid compound as claimed in claim 1 wherein, The reaction temperature of the oxidation reaction is 90 DEG C, and the reaction time is 6 h.

4. The process for synthesis of benzoic acid compound as claimed in claim 1, wherein, The synthesis process of the benzoic acid compound comprises the following preparation steps: The compound of formula I and water are mixed, and hydrogen peroxide is added, and povidone iodine is added at -5-0 DEG C to perform an oxidation reaction, wherein the reaction temperature is 70-100 DEG C, and the reaction time is 6-12 h, to obtain a reaction solution containing the compound of formula II; The reaction solution is first filtered by diatomite, the filtrate is collected, and saturated sodium bicarbonate aqueous solution is added to the filtrate to obtain a filtrate containing saturated sodium bicarbonate aqueous solution; then the filtrate containing saturated sodium bicarbonate aqueous solution is extracted by an organic solvent, the aqueous phase is collected, and the pH value of the aqueous phase is adjusted to 4-6 to obtain an aqueous phase with a pH value of 4-6; and finally, the aqueous phase with a pH value of 4-6 is extracted, dried, and concentrated to obtain the compound of formula II.

5. The process for synthesis of benzoic acid compound as claimed in claim 1, wherein, In the compound of formula I, R is any one of -CH3, -OCH3, and -i-PrO.

6. The process for synthesis of benzoic acid compounds as claimed in claim 1 wherein, The compound of formula II is 3-methylbenzoic acid, 4-methoxybenzoic acid, 4-methylbenzoic acid, or 4-isopropoxybenzoic acid.

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