Method for synthesizing 2-nitrotoluene compound through catalyst-free photochemical decarboxylation

Abstract

The invention relates to a method for synthesizing a 2-nitrotoluene compound through catalyst-free photochemical decarboxylation, which is characterized in that cheap carboxylic acid is used as a raw material, air is used as an oxidant, 2, 4, 6-trimethylpyridine is used as an acid-binding agent, tetrabutylammonium chloride is used as a zwitterionic compound, an exogenous photosensitizer is not used, and the catalyst-free photochemical decarboxylation method is used for synthesizing the 2-nitrotoluene compound. An EDA complex is formed through neutralization of carboxylic acid and an acid-binding agent and subsequent electron donor-acceptor, mild activation of carboxylic acid is realized through electron transfer under illumination, and the 2-nitrotoluene compound is synthesized. An efficient, green and environment-friendly synthesis route with atom economy, simple steps, low price and a wide application range is provided for the 2-nitrotoluene compound so as to meet the requirements of industrial application, and the synthesis method is more environmentally friendly and wide in application range.

Description

TECHNICAL FIELD

[0001] The present application relates to a method for synthesizing 2-nitrotoluene compounds by photocatalyst-free decarboxylation, belonging to the technical field of organic photochemical synthesis. BACKGROUND

[0002] 2-nitrotoluene compounds are an important class of chemical raw materials, widely used in dyes, coatings, plastics, pesticides and pharmaceuticals, etc. This class of compounds can be used to produce o-toluidine, dimethylamine, etc. In the pharmaceutical industry, it is often used to produce nifedipine, pain, imipramine hydrochloride, bromhexine hydrochloride, dicloxacillin sodium, etc. In addition, 2,4-dinitrotoluene is also an important raw material for the preparation of explosives.

[0003] The current literature reported method for preparing 2-nitrotoluene is mainly the nitration of toluene in mixed acid (toluene nitration method), however, the product after nitration is a mixture of 2-nitrotoluene, 3-nitrotoluene and 4-nitrotoluene. Due to the small difference in polarity of the three substances, it is difficult to separate them by column chromatography and other methods. Therefore, the crude nitrotoluene is mainly separated by crude distillation and crystallization by taking advantage of the boiling point difference of different products. However, the distillation separation method is relatively complex, and requires repeated distillation and rectification. Therefore, it is urgent to develop a green catalytic, low-cost and high-yield method for preparing 2-nitrotoluene.

[0004] 2-nitrobenzoic acid compounds are a common bulk chemical, due to their low price, stability to air and moisture, and wide application prospect for preparing 2-nitrotoluene by decarboxylation hydrogenation reaction. The decarboxylation hydrogenation process of carboxylic acid usually requires the use of equivalent chemical oxidants (such as potassium persulfate, etc.), resulting in high cost, poor atom economy and complex operation. Using air as an oxidant to realize decarboxylation hydrogenation has more practical value, however, the oxidation potential of carboxylic acid is as high as +2.0V vs SCE, and air is difficult to directly oxidize it. The current catalytic strategy mainly adds metal catalysts (such as rhodium, gold, palladium, copper, etc.) to the reaction system, but the use of metal catalysts will cause problems such as rising reaction cost and complex post-treatment.

[0005] Therefore, it is of great significance to find a method for preparing 2-nitrotoluene compounds by decarboxylation hydrogenation with air as an oxidant and without metal catalysts, and with simple post-treatment. SUMMARY

[0006] In view of the deficiencies of the prior art, especially the complex post-treatment of the existing toluene nitration method, the metal catalysts for the decarboxylation hydrogenation of arylacetic acid resulting in high reaction cost, complex reaction system and operation, low atom efficiency and environmental unfriendliness, the present application provides a method for synthesizing 2-nitrotoluene compounds by photocatalyst-free decarboxylation.

[0007] The present application is realized by the following technical scheme:

[0008] The application discloses a method for synthesizing 2-nitrotoluene compound through catalyst-free photochemical decarboxylation, and comprises the following steps.

[0009] The carboxylic acid, the acid-binding agent and the zwitterionic compound are sequentially added into the solvent, and the mixture is stirred at room temperature; air is used as an oxidant, and the mixture is subjected to reaction under irradiation without catalyst; after the reaction is completed, the reaction solution is concentrated, and the organic phase is separated and purified to obtain the 2-nitrotoluene compound.

[0010] According to the application, the solvent is preferably acetonitrile.

[0011] According to the application, the acid-binding agent is preferably 2,4,6-trimethylpyridine.

[0012] According to the application, the carboxylic acid is preferably 2-nitrobenzoic acid, and has the structure shown in the following formula (I).

[0013]

[0014] In the formula I, R 1 is selected from a hydrogen atom, a methyl group or a nitro group.

[0015] According to the application, the zwitterionic compound is preferably tetrabutylammonium chloride.

[0016] The application uses 2,4,6-trimethylpyridine as an acid-binding agent, uses an electron donor-acceptor (EDA) photocatalytic mode, protonates the carboxylic acid to the 2,4,6-trimethylpyridine to generate a carboxylic acid anion and a 2,4,6-trimethylpyridine proton salt, and then the two form an EDA complex. The tetrabutylammonium chloride is used as a zwitterionic compound to stabilize the EDA complex and improve the electron transfer efficiency, so that the yield is greatly improved.

[0017] According to the application, the molar concentration of the zwitterionic compound in the mixture is 0.05-1.0 mmol / mL.

[0018] According to the application, the molar ratio of the carboxylic acid to the zwitterionic compound is 1:(1-10).

[0019] Further preferably, the molar ratio of the carboxylic acid to the zwitterionic compound is 1:(1-5).

[0020] Most preferably, the molar ratio of the carboxylic acid to the zwitterionic compound is 1:3.

[0021] According to the application, the molar ratio of the carboxylic acid to the acid-binding agent is 1:(1-7).

[0022] Further preferably, the molar ratio of the carboxylic acid to the acid-binding agent is 1:(1-5).

[0023] Most preferably, the molar ratio of the carboxylic acid to the acid-binding agent is 1:2.

[0024] According to the present application, preferably, the wavelength of the light is 365-420 nm.

[0025] Most preferably, the wavelength of the light is 395 nm.

[0026] According to the present application, preferably, the intensity of the light is 5-100 W.

[0027] Most preferably, the intensity of the light is 5 W.

[0028] According to the present application, preferably, the reaction temperature is 20-50℃, the reaction time is 24-72 h, and the reaction is carried out in air.

[0029] According to the present application, preferably, the organic phase separation and purification are carried out by rotary evaporation to remove the solvent, and then the residue is purified by silica gel column chromatography, and the eluent of the silica gel column is ethyl acetate: petroleum ether = 1:10-1:50.

[0030] A 2-nitrotoluene compound is prepared by the above method.

[0031] According to the present application, preferably, the 2-nitrotoluene compound has the structure shown in formula (II):

[0032]

[0033] In formula (II), R 1 is selected from a hydrogen atom, a methyl group, and a nitro group.

[0034] The reaction route of the present application is as follows:

[0035]

[0036] A preferred embodiment of the present application is as follows:

[0037] A method for synthesizing a 2-nitrotoluene compound by photocatalyst-free photochemical decarboxylation, comprising the following steps:

[0038] (1) 0.2 mmol of a 2-nitrobenzoic acid substrate, 0.4 mmol of 2,4,6-trimethylpyridine, 0.6 mmol of tetrabutylammonium chloride, and 4 mL of acetonitrile are sequentially added to a flask, and then the mixture is subjected to a 395 nm, 5 W light irradiation reaction under air at 25℃ for 48 h;

[0039] (2) After the reaction is completed, the solvent of the reaction solution is removed by a rotary evaporator, and the residue is purified by flash silica gel column chromatography to obtain the product.

[0040] Principles of the present application:

[0041] The method of the present application uses cheap 2-nitrobenzoic acid as raw material, air as oxidant, 2,4,6-trimethylpyridine as acid binding agent, and utilizes the photo-catalytic mode of electron donor-acceptor (EDA), i.e. the carboxylic acid is protonated with 2,4,6-trimethylpyridine to form carboxylic acid anion and proton salt of 2,4,6-trimethylpyridine, which forms EDA complex through electron donor-acceptor (EDA). The complex easily undergoes electron transfer under light to form carboxyl radical and acid binding agent reduction product, and the carboxyl radical spontaneously removes CO2 to form benzyl radical. Due to the electronic effect of nitro group, this benzyl radical is not easy to couple with oxygen, and is more likely to capture hydrogen atoms from acetonitrile solvent to form 2-nitrotoluene. In order to meet the requirements of industrial application, the organic photochemical synthesis method of the present application does not need to add additional photosensitizer, is more green, environmentally friendly and has wide application range, and the reaction mechanism is as follows:

[0042]

[0043] Technical features and advantages of the present application:

[0044] 1. The method of the present application uses cheap 2-nitrobenzoic acid as raw material, air as oxidant, 2,4,6-trimethylpyridine as acid binding agent, and tetrabutylammonium chloride as zwitterionic compound, without external photosensitizer. Through the neutralization of carboxylic acid and acid binding agent and the subsequent formation of EDA complex through electron donor-acceptor mode, electron transfer occurs under light to achieve mild activation of carboxylic acid, realizing the direct oxidation decarboxylation hydrogenation of carboxylic acid with air as oxidant, successfully synthesizing 2-nitrotoluene compounds, without catalyst, low cost, simple operation, high yield, simple post-treatment, up to 85%, environmentally friendly, and having good application prospect. It is a new type of catalyst-free decarboxylation hydrogenation of 2-nitrobenzoic acid to prepare 2-nitrotoluene compounds.

[0045] 2. The present application adopts the electron donor-acceptor (EDA) complex mode of carboxylic acid and 2,4,6-trimethylpyridine to realize photo-catalytic synthesis, without additional catalyst, which will not cause safety problems and catalyst residue problems.

[0046] 3. The present application avoids the use of oxidants and toxic and expensive catalysts, has high reaction yield, and the reaction system is simple and safe.

[0047] 4、The application not only avoids the use of catalyst, greatly reduces the reaction cost, and has the advantages of simple operation, and avoids the use of chemical oxidant, uses air as green oxidant, saves cost, and avoids the pollution of by-products to the environment after the action of chemical oxidant and the complexity of post-treatment.

[0048] 5、The 2,4,6-trimethylpyridine of the application is used as an acid-binding agent, utilizes the photocatalytic mode of electron donor-acceptor (EDA), protonates the carboxylic acid on the 2,4,6-trimethylpyridine to generate carboxylic acid anion and 2,4,6-trimethylpyridine proton salt, and then the two form an EDA complex, and tetrabutylammonium chloride is used as an amphoteric ion compound to stabilize the complex, so that the yield is greatly improved. BRIEF DESCRIPTION OF DRAWINGS

[0049] Figure 1 The preparation method of 2-nitrotoluene prepared in Example 1 of the application is as follows: 1 H NMR chart.

[0050] Figure 2 The preparation method of 2-nitrotoluene prepared in Example 1 of the application is as follows: 13 C NMR chart.

[0051] Figure 3 The preparation method of 2,3-dimethyl nitrobenzene prepared in Example 2 of the application is as follows: 1 H NMR chart.

[0052] Figure 4 The preparation method of 2,3-dimethyl nitrobenzene prepared in Example 2 of the application is as follows: 13 C NMR chart.

[0053] Figure 5 The preparation method of 2,4-nitrotoluene prepared in Example 3 of the application is as follows: 1 H NMR chart.

[0054] Figure 6 The preparation method of 2,4-nitrotoluene prepared in Example 3 of the application is as follows: 13 C NMR chart. DETAILED DESCRIPTION

[0055] The content of the application will be further described below through specific examples, but is not a limitation of the application.

[0056] The raw materials used in the examples can be purchased in the market, or can be prepared according to the prior art.

[0057] Example 1:

[0058] The preparation method of 2-nitrotoluene is as follows:

[0059]

[0060] Into a 10 mL flask was added 2-nitrobenzoic acid 0.2 mmol, 2,4,6-trimethylpyridine 0.4 mmol, tetrabutylammonium chloride 0.6 mmol, acetonitrile 4 mL, under the atmosphere of air, 395 nm, 5W light irradiation reaction for 48 h, TLC tracking monitoring; after the reaction was completed, the solvent was removed by rotary evaporator, the residue was purified by silica gel column chromatography (a mixture of petroleum ether and ethyl acetate as the mobile phase) to obtain the product (yellow liquid), yield 80%.

[0061] The product was characterized by 1 H NMR chart, 13 C NMR chart respectively Figures 1-2 .

[0062] 1 H NMR (400 MHz, CDCl3) δ 7.96 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.49 (td, J = 7.6 Hz, 1.2 Hz, 1H), 7.36-7.31 (m, 2H), 2.60 (s, 3H).

[0063] 13 C NMR (101 MHz, CDCl3) δ 133.67, 133.12, 132.87, 127.00, 124.74, 20.52.

[0064] Example 2:

[0065] The preparation method of 2,3-dimethyl nitrobenzene is as follows:

[0066]

[0067] Into a 10 mL flask was added 2-nitrobenzoic acid 0.2 mmol, 2,4,6-trimethylpyridine 0.4 mmol, tetrabutylammonium chloride 0.6 mmol, acetonitrile 4 mL, under the atmosphere of air, 395 nm, 5W light irradiation reaction for 48 h, TLC tracking monitoring; after the reaction was completed, the solvent was removed by rotary evaporator, the residue was purified by silica gel column chromatography (a mixture of petroleum ether and ethyl acetate as the mobile phase) to obtain the product (yellow liquid), yield 80%.

[0068] The product was characterized by 1 H NMR chart, 13 C NMR chart respectively Figure 4 .

[0069] 1H NMR (400 MHz, CDCI3) δ 7.59 (d, J = 8.4 Hz, 1 H), 7.36 (d, J = 7.6 Hz, 1 H), 7.20 (t, J = 8.0 Hz, 1 H), 2.38 (s, 3 H), 2.37 (s, 3 H).

[0070] 13 C NMR (101 MHz, CDCI3) δ 139.56, 133.79, 130.79, 126.14, 121.80, 20.62, 15.34.

[0071] Example 3:

[0072] 2,4-nitrobenzene preparation method, the steps are as follows:

[0073]

[0074] In 10 mL reaction tube, 2,4-nitrobenzoic acid 0.2 mmol, 2,4,6-trimethylpyridine 0.4 mmol, tetrabutylammonium chloride 0.6 mmol, acetonitrile 4 mL, in the air atmosphere, 395 nm, 5W light illumination reaction 48 h, TLC tracking monitoring; after the reaction is completed, the solvent is removed by rotary evaporator, and the residue is purified by silica gel column chromatography (the mixture of petroleum ether and ethyl acetate as the mobile phase) to obtain the product (light yellow solid), the yield is 71%.

[0075] The product of 1 H NMR chart, 13 C NMR chart respectively Figures 5-6 .

[0076] 1 H NMR (400 MHz, CDCI3) δ 8.82 (d, J = 2.4 Hz, 1 H), 8.35 (dd, J = 8.4 Hz, 2.4 Hz, 1 H), 7.59 (d, J = 9.2 Hz, 1 H), 2.73 (s, 3 H).

[0077] 13 C NMR (101 MHz, CDCI3) δ 149.16, 146.52, 140.88, 134.16, 127.13, 120.35, 20.83.

[0078] Comparative example 1

[0079] The preparation method is the same as that described in example 1, except that:

[0080] Use nitrogen instead of air atmosphere, other conditions are unchanged, according to example 1; due to the lack of oxidant, no reaction occurs in the nitrogen atmosphere.

[0081] Comparative Example 2

[0082] The preparation method is the same as described in Example 1, except that:

[0083] The reaction is carried out according to Example 1 without using light, and other condition parameters remain unchanged. Without using light, the complex cannot undergo electron transfer, and thus cannot further react to generate 2-nitrotoluene compounds. Therefore, no reaction occurs without using light, which also verifies the generation of EDA complex.

[0084] Comparative Example 3

[0085] The preparation method is the same as described in Example 1, except that:

[0086] The reaction is carried out according to Example 1 without adding tetrabutylammonium chloride, and other condition parameters remain unchanged. Without adding tetrabutylammonium chloride, the generated complex cannot be stabilized, and thus the subsequent reaction does not occur.

[0087] Comparative Example 4

[0088] The preparation method of 2-nitrotoluene compounds is the same as described in Example 1, except that:

[0089] Tetrabutylammonium hexafluorophosphate is used instead of tetrabutylammonium chloride, and other condition parameters remain unchanged. The product yield is 2% according to Example 1. Since tetrabutylammonium hexafluorophosphate cannot well stabilize the complex, the product yield is extremely low.

[0090] Comparative Example 5

[0091] The preparation method of 2-nitrotoluene compounds is the same as described in Example 1, except that:

[0092] Quinoline is used instead of 2,4,6-trimethylpyridine, and other condition parameters remain unchanged. The product yield is 10% according to Example 1. Since the in-situ generated quinoline proton salt acts as an electron acceptor, it cannot guarantee the electron transfer between the complexes, resulting in a low product yield.

[0093] Comparative Example 6

[0094] The preparation method of 2-nitrotoluene compounds is the same as described in Example 1, except that:

[0095] Trichloromethane is used instead of acetonitrile, and other condition parameters remain unchanged. The product yield is 12% according to Example 1. Since trichloromethane cannot well stabilize the complex, the product yield is low.

[0096] Comparative Example 7

[0097] The preparation method of the 2-nitrotoluene compound in Example 1 is different in that:

[0098] The reaction time is 72 h, other conditions are unchanged, and the process is carried out according to Example 1; the yield of the product is 78%, and compared with Example 1, it can be seen that even if the reaction time is prolonged, the yield of the product does not increase, and basically remains unchanged. With the prolongation of the reaction time, the energy consumption increases, therefore, the optimal reaction time of the present application is 48 h.

[0099] In summary, in the nitrogen atmosphere, no light or without adding tetrabutylammonium chloride, no reaction or very low yield; tetrabutylammonium hexafluorophosphate instead of tetrabutylammonium chloride as a zwitterionic compound, quinoline instead of 2,4,6-trimethylpyridine as an acid binding agent, and chloroform instead of acetonitrile, the yield of the product is less than that of the present application. Therefore, the air atmosphere, the wavelength of light, the zwitterionic compound, the acid binding agent and the reaction time are the keys to obtaining 2-nitrotoluene compounds with high yield.

Claims

1. A method for synthesizing 2-nitrotoluene compounds by photochemical decarboxylation without a catalyst, comprising the following steps: Carboxylic acid, an acid-binding agent, and a zwitterionic compound are sequentially added to a solvent and stirred at room temperature to obtain a mixed solution. Air is used as an oxidant, and the mixed solution is reacted under light without a catalyst. After the reaction is completed, the reaction solution is concentrated, and the organic phase is separated and purified to obtain a 2-nitrotoluene compound.

2. The method according to claim 1, characterized in that The solvent is acetonitrile, and the acid-binding agent is 2,4,6-trimethylpyridine.

3. The method according to claim 1, characterized in that The carboxylic acid is 2-nitrophenylacetic acid, having the structure shown in the following formula (I): In Formula I, R 1 is selected from a hydrogen atom, a methyl group or a nitro group.

4. The method according to claim 1, wherein The zwitterionic compound is tetrabutylammonium chloride.

5. The method according to claim 1, wherein The molar concentration of the zwitterionic compound in the mixed solution is 0.05 to 1.0 mmol / mL.

6. The method according to claim 1, characterized in that The molar ratio of the carboxylic acid to the zwitterionic compound is 1:(1-10), preferably, the molar ratio of the carboxylic acid to the zwitterionic compound is 1:(1-5), and most preferably, the molar ratio of the carboxylic acid to the zwitterionic compound is 1:

3.

7. The method according to claim 1, characterized in that The molar ratio of carboxylic acid to the acid binding agent is 1:(1-7), preferably, the molar ratio of carboxylic acid to the acid binding agent is 1:(1-5), and the molar ratio of carboxylic acid to the acid binding agent is 1:

2.

8. The method according to claim 1, characterized in that The wavelength of the light is 365-420 nm, and the intensity of the light is 5-100 W.

9. The method according to claim 1, characterized in that The reaction temperature is 20-50° C., the reaction time is 24-72 hours, and the reaction is carried out under air conditions. The organic phase is separated and purified by rotary evaporation to remove the solvent, and the residue is purified by silica gel column chromatography. The eluent of the silica gel column is ethyl acetate: petroleum ether = 1:10-1:

50.

10. A 2-nitrotoluene compound prepared by the method according to any one of claims 1 to 9. It has the structure shown in formula (II): In formula (II), R 1 Selected from hydrogen atom, methyl group, nitro group.

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