A method for synthesizing benzil or its derivatives from green benzoine or its derivatives

Abstract

The present application belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing benzil or its derivative from green oxidation of benzoin or its derivative. A complex compound is prepared from ethylenediaminetetraacetic acid disodium salt and a metal salt as a catalyst, then benzoin or its derivative and the catalyst are added into a reaction container, ethanol and TBAB are added, H2O2 is added dropwise, and the reaction is heated by magnetic stirring oil bath, so that benzoin or its derivative is oxidized into benzil or its derivative, the purity of the product is greater than or equal to 97%, the selectivity is 95%, and the yield is as high as 90.5%. The method has the advantages of strong reaction selectivity, high yield, good color of product, high purity, mild reaction condition, few by-products, simple post-treatment, green and non-toxic substances of solvent and oxidant, and repeated use of the catalyst, and the reaction not only meets the requirements of green chemistry, but also has important significance for energy saving and emission reduction.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing benzil or its derivative from green oxidation of benzoin or its derivative. BACKGROUND

[0002] Although the traditional technology for synthesizing benzil from direct oxidation of benzoin is classic, it is greatly limited in further application due to low efficiency and complicated post-treatment. In recent years, new technologies, new methods and new catalysts have created a new field of organic synthesis with the characteristics of high efficiency, rapidness, high selectivity and simple operation. Many chemical workers have actively explored economical, simple and efficient oxidation means and searched for new green catalysts in the research on oxidation of benzoin around the idea of greenness. Compared with conventional reaction conditions, these new reactions have obvious time reduction and yield improvement, and have certain theoretical and practical significance, and also provide a green and effective new way for improving the efficiency of oxidation of benzoin and expanding its application range.

[0003] Upon reviewing the research achievements of oxidation of benzoin in recent years, we find that there are still many defects. First, in the research on the route for synthesizing benzil from non-catalytic oxidation, although clean oxidants such as oxygen, hydrogen peroxide and ozone have been used to replace traditional high-pollution oxidants such as dilute nitric acid and potassium permanganate, these oxidants have defects such as weak oxidizing property and complex reaction conditions, and are difficult to be used in large scale or industrialization. Second, the oxidation efficiency of benzoin is improved by loading a carrier, but the improvement of the performance of the oxidation reaction system by the increase of the economic cost is very small. Third, although metal complexes as catalysts for oxidation of benzoin have certain research progress, they are still in the research stage. For example, the Salen catalyst which has been studied a lot has low stability, and most researchers tend to use DMF as a solvent, but DMF is not recommended to be used as a solvent in actual industry because it is highly toxic, heavily polluting, has high boiling point and is difficult to be recycled, and does not meet the environmental protection requirements of green chemistry. In addition, the metal salen complex has high preparation cost and low thermal stability, which brings certain requirements for storage and transportation.

[0004] The present application selects oxidants, solvents and catalysts from the perspective of green chemistry, and innovates the synthesis of benzil from oxidation of benzoin. Among them, hydrogen peroxide is a commonly used green oxidant, and its oxidation product is usually water which is non-toxic to the environment, but its oxidizing property is weak, the direct oxidation efficiency is low, and benzoin is easily decomposed into benzoic acid under high concentration; the thermal stability of the coordination compound MNaEDTA is higher than that of the Salen catalyst, and it is simple to prepare and cheaper; ethanol is a renewable green solvent, and the use of ethanol instead of toxic and difficult-to-recycle DMF as a solvent is both economic and environmentally friendly. SUMMARY

[0005] The present application aims to overcome the shortcomings of the prior art, such as poor selectivity, low yield, high toxicity, low product purity, complex post-treatment, difficult catalyst recovery, high cost, and heavy pollution, and to provide a method for green synthesis of benzil and its derivatives with high yield and high selectivity, using a coordination compound formed by the reaction of a metal salt and disodium ethylenediaminetetraacetate as a catalyst, H2O2 as a green oxidant, and ethanol as a solvent.

[0006] The present application provides a method for green oxidation of benzoin or its derivatives to synthesize benzil or its derivatives, which first generates a coordination compound of metal ethylenediaminetetraacetate and sodium by the reaction of a metal salt and disodium ethylenediaminetetraacetate, and then catalyzes the generation of free radical benzoin with oxidizing properties by hydrogen peroxide to generate benzil, and the reduced metal is oxidized to the original valence ion under the action of the oxidizing free radical.

[0007] The reaction formula is as follows:

[0008]

[0009] R is any one of aryl, heteroaryl, substituted aryl, and substituted heteroaryl; aryl is selected from one of phenyl, naphthyl, phenanthryl, and anthryl; heteroaryl is selected from one of pyrrolyl, furanyl, thienyl, pyrazolyl, and imidazolyl.

[0010] The specific operation method for synthesizing benzil from benzoin is as follows:

[0011] (1) The coordination compound generated by the reaction of a metal salt and disodium ethylenediaminetetraacetate is used as a catalyst;

[0012] (2) Benzoin or its derivatives and the catalyst are added to a reaction container, ethanol solvent and 1% TBAB (tetrabutylammonium bromide) are added, H2O2 is added dropwise, magnetic stirring and oil bath heating are performed, TLC detection is performed until the reaction is completed, post-treatment and recrystallization are performed after the reaction, and the reaction product benzil or its derivatives is collected.

[0013] Further, the specific preparation method of the catalyst is as follows: disodium ethylenediaminetetraacetate salt and a metal salt are added to a beaker, water is added to the beaker, heating is performed until the solid is dissolved, sodium bicarbonate is added to the solution to adjust the pH to 5, heating is performed for 30 minutes, the liquid is cooled, and then the catalyst of the coordination compound formed by the metal salt and Na2EDTA is obtained by filtration, washing with methanol, and drying, which is denoted as MNaEDTA or MEDTA.

[0014] The metal salt in the catalyst includes, but is not limited to, one or more of copper salt, iron salt, cadmium salt, nickel salt, cobalt salt, zinc salt, and manganese salt.

[0015] The amount of reaction hydrogen peroxide is 1-20 mL / 1 mmol benzoin. Further preferably, 6-10 mL / 1 mmol benzoin.

[0016] The concentration and amount of ethanol are not particularly limited, and anhydrous ethanol or ethanol solution can be used according to the actual situation.

[0017] The amount of reaction catalyst is 0.01-0.20 g / 1 mmol benzoin. Further preferably, 0.08-0.20 g / 1 mmol benzoin.

[0018] The amount of reaction 1% TBAB (1% mass concentration of aqueous tetrabutylammonium bromide) is 1-10 mL / 1 mmol benzoin. Further preferably, 2.5-10 mL / 1 mmol benzoin.

[0019] The reaction temperature is 20-100°C, and the reaction time is 0.5-5 h. Further preferably, 50-70°C, 1.5-2.5 h.

[0020] The solvent used for recrystallization after reaction is one or several of water, methanol, ethanol, diethyl ether, acetonitrile, and chloroform.

[0021] The benzil synthesized by the green oxidation of benzoin has the following characteristics:

[0022] 1. H2O2 is used as an oxidant, and its oxidation product is usually water, which is non-toxic to the environment. It is a cheap, easy-to-get green oxidant.

[0023] 2. The coordination compound M(Na)EDTA has higher thermal stability than the Salen catalyst, and is simple to prepare, inexpensive, non-toxic, and can be repeatedly used.

[0024] 3. Ethanol is a renewable green solvent. Using ethanol to replace the toxic and difficult-to-recycle DMF as a solvent is both economical and environmentally friendly.

[0025] 4. The reaction conditions are mild, the by-products are few, the raw materials are easy to obtain, the reaction time is short, the operation is simple, the post-treatment is easy, the color of the product is good, and the purity is high. The reaction can realize large-scale industrial production, and has important significance in greenization and energy saving and emission reduction. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 Infrared spectra of FeNaEDTA and Na2EDTA.

[0027] Figure 2 Catalyst recycling effect diagram of Example 2.

[0028] Figure 3 Effect of reaction time on the yield of benzil synthesized by oxidation of benzoin.

[0029] Figure 4 The effect of reaction temperature on the synthesis of ethyl coumarin-3-carboxylate.

[0030] Figure 5 The effect of catalyst dosage on the yield of benzoyl synthesis from oxidized benzoin.

[0031] Figure 6 The effect of H2O2 dosage on the yield of benzoyl in the synthesis of benzoin.

[0032] Figure 7 shows the effect of 1% TBAB dosage on the synthesis of ethyl coumarin-3-carboxylate. Detailed Implementation

[0033] The embodiments of the present invention will be described in detail below with reference to examples, the purpose of which is to provide a better understanding of the content of the present invention. However, the embodiments do not limit the scope of the present invention in any way. Improvements made by those skilled in the art within the scope of the claims of the present invention also fall within the rights and protection scope of the present invention.

[0034] Example 1

[0035] Catalysts prepared by reacting metal salts with disodium ethylenediaminetetraacetate

[0036] Take 3.36 g (0.1 mol) of disodium ethylenediaminetetraacetate and 2.70 g (0.01 mol) of ferric chloride hexahydrate and add them to a beaker. Add 20 ml of water to a 250 ml beaker and heat until the solid dissolves. Then add sodium bicarbonate to the solution to adjust the pH to 5, heat for 30 minutes, cool the liquid, filter, wash with methanol, dry, and weigh to obtain 5.78 g of pale yellowish-brown crystalline powder (yield 95.3%) for later use.

[0037] The infrared spectra of FeNaEDTA and Na2EDTA are as follows: Figure 1 As shown, the coordination of Fe with EDTA leads to ν (C＝O) From 1634cm -1 Shift to a high wavenumber of 1641 cm⁻¹ -1 Blue shift occurs during movement, ν (C-O) Then from 1401cm -1 Move to a low wavenumber of 1388cm -1 This indicates that the carboxyl group in the ligand coordinated with Fe(III). Due to the contribution of the shared electrons of the nitrogen atom to the iron atom, the CN bond dipole increased, causing the CN peak to shift to 1102 cm⁻¹. -1 and 1258cm -1 . ν (-OH) At 3497cm -1The peak number of the infrared spectrum of the complex FeNaEDTA is reduced, indicating that the spatial structure of the complex is more regular than the raw material, and the coordination is successful.

[0038] Example 2

[0039] Take 0.531 g (2.5 mmol) of benzoin and 0.1 g (0.27 mmol) of FeNaEDTA into a 50 ml three-necked flask, then add ethanol and 1% TBAB, insert a spherical condenser, and heat to 60°C under magnetic stirring. Then add 10 mL of H2O2 (mass concentration 35%) through a dropping funnel, and dropwise add within 10 min. Continue to heat and stir until the reaction is completed by TLC detection. Cool slightly, filter out FeNaEDTA, add 10 ml of ice water to the filtrate, and let the solid precipitate. Then filter, recrystallize, dry, and obtain yellow needle-shaped crystals 0.441 g, with a yield of 90.5%, a selectivity of 95%, and a purity of 97%.

[0040] Structure and characterization of the obtained solid:

[0041]

[0042] Benzoin is a yellow needle-shaped crystal with a melting point of 94-96°C; IR (KBr, v, cm -1 ): 3065, 1666, 1591, 1448, 1318, 1210, 873, 720, 689, 635, wherein the hydroxyl absorption peak at 3350 cm -1 does not appear, the carbonyl absorption peak at 1666 cm -1 is broadened, indicating that benzoin is oxidized to benzoin. In 1 H NMR (400M, CDC13, δ): 7.98 (d, 2H, Ar-H), 7.66 (t, 4H, Ar-H), 7.51 (t, 4H, Ar-H).

[0043] Reusability of the catalyst

[0044] The experimental operation is the same as above, and the other conditions remain unchanged. The reusability of the catalyst is investigated, as shown in Figure 2 . It can be seen from Figure 2 that the yield of the reaction is still above 80% when the catalyst is reused for 5 times. It can be seen that the catalyst has the advantages of high catalytic efficiency, strong selectivity, and repeated use, meeting the requirements of green catalytic recycling.

[0045] Example 3

[0046] The other operations are the same as in Example 2, and the effect of reaction time on the yield of oxidized benzoin to synthesize benzoin is investigated, as shown in Figure 3 . It can be seen fromFigure 3 It can be seen that the yield of benzoyl synthesis gradually increases with increasing reaction time. When the reaction time is 2 hours, the reaction reaches equilibrium, and further extending the reaction time does not significantly change the yield. This is because initially, with increasing reaction time, the number of highly oxidizing ·O2, ·O, and ·OH radicals produced by FeNaEDTA catalyzing H2O2 increases, as does the number of O2 molecules, leading to increased effective collisions and thus increased yield. However, once the reaction reaches equilibrium, the active molecules become saturated, and both side reactions and the reverse reaction gradually intensify. Further extending the reaction time has little effect on the yield and only increases energy consumption. Therefore, the optimal reaction time is 2 hours.

[0047] Example 4

[0048] Other procedures are the same as in Example 2. The effect of different reaction temperatures on the yield of benzoyl oxidase to benzoin is compared. Figure 4 .Depend on Figure 4 It is evident that temperature has a significant impact on the reaction yield. At low temperatures, the reaction rate is slow and the yield is low due to the fewer active molecules. As the reaction temperature increases, the number of active molecules increases, the probability of effective intermolecular collisions increases, and the yield increases significantly. However, the reaction yield decreases slightly when the temperature exceeds 60℃. This may be because the decomposition rate of H2O2 is accelerated at higher temperatures, and the generated oxygen rapidly enters the system. Alternatively, it may be due to the increased reverse reaction and side reactions at higher temperatures. Therefore, a reaction temperature of 60℃ is optimal.

[0049] Example 5

[0050] Other procedures are the same as in Example 2. The effect of the amount of FeNaEDTA catalyst on the yield of benzoyl oxidase to benzoyl is compared in [see Example 2]. Figure 5 .Depend on Figure 5 It can be seen that the reaction yield is low when the catalyst dosage is low. This may be because when the catalyst dosage is low, the number of H2O2 molecules decomposed is small, the concentration of oxygen molecules or oxygen-containing free radicals is low, and the probability of effective collisions between molecules is also small, resulting in a low yield. As the catalyst dosage gradually increases, the reaction yield gradually increases at the beginning, but after exceeding 0.10 g, although the yield increases slightly, it has almost no effect on the overall reaction yield. This may be because after the active oxygen free radicals or oxygen molecules reach a certain level, Fe... Ⅲ Fe in NaEDTA Ⅲ This is due to its weak oxidizing effect. Therefore, a catalyst dosage of 0.10g is optimal.

[0051] Example 6

[0052] Other procedures are the same as in Example 2. The effect of H2O2 dosage on the yield of benzoyl oxidase in synthesis is compared (see Example 2). Figure 6 .Depend on Figure 6It is known that when the amount of oxidant H2O2 is small, the number of free radicals with strong oxidizing properties ·O2, ·O, and ·OH generated by FeNaEDTA catalysis is small, the concentration of active molecules in the system is low, the probability of effective collision is low, and the reaction yield is low. However, if too much H2O2 is used, due to its own characteristics, it is easy to decompose benzoin into benzoic acid at high concentrations, thus reducing the reaction yield. Therefore, the amount of H2O2 used is more suitable at about 10 mL.

[0053] Example 7

[0054] Other procedures are the same as in Example 2. The effect of 1% TBAB dosage on the yield of benzoyl oxidase in the synthesis of benzoyl is compared in [see Example 2]. Figure 7 .Depend on Figure 7 It is known that the reaction yield is low without the co-catalytic effect of 1% TBAB, possibly due to the co-catalytic effect of TBAB phase transfer catalysis. However, excessive dosage will dilute the reaction and reduce the concentration of active molecules, which may slightly decrease the reaction yield. Therefore, the appropriate dosage of 1% TBAB is 5 mL / 1 mmol benzoin.

[0055] Example 8

[0056] The synthesis of furoyl is the same as in Example 2, except that benzoin is replaced with furoylin.

[0057] Structure and characterization of the obtained solid

[0058]

[0059] Yellow solid, yield 88.6%; mp 163.5–164.8℃; 1 HNMR (400MHz, CDCl3, ppm) δ / 10 -6 :6.61(m,2H),7.65(m,4H).

[0060] Example 10

[0061] The synthesis of 4,4'-difluorobenzoin was performed by replacing benzoin with 4,4'-difluorobenzoin, otherwise the same as in Example 2.

[0062] Structure and characterization of the obtained solid

[0063]

[0064] Yellow solid, yield 91.3%, purity 97%, mp 117.7~119.2; 1 HNMR (400MHz, CDCl3, ppm) δ / 10 -6 : 8.02~8.06 (m, 4H, Ar-H), 7.16~7.28 (m, 4H, Ar-H).

[0065] Example 11

[0066] Synthesis of 4,4'-dimethoxybenzil, benzoin was replaced by 4,4'-dimethoxybenzil, other operations were the same as Example 2.

[0067] Structure and characterization of the obtained solid

[0068]

[0069] Yellow solid, yield 90.2%; m.p. 131.5-133.6°C; 1 HNMR (400MHz, CDC13, ppm) δ / 10 -6 : 3.81 (s, 6H, 2CH3-), 6.93, 7.81 (dd, 8H, J=8Hz, Ar-H).

[0070] Example 12

[0071] Synthesis of 4,4'-dinitrobenzil, benzoin was replaced by 4,4'-dinitrobenzil, other operations were the same as Example 2.

[0072]

[0073] Yellow solid, yield 87.3%; m.p. 214.6-216.5°C; IR (KBr, v / cm -1 ): 1661, 1622, 1562, 356, 864, 748; 1 HNMR (400MHz, CDC13, ppm) δ / 10 -6 : 7.86, 812 (dd, 8H, J=8Hz, ArH).

[0074] Comparative example

[0075] Other operations were the same as Example 2, the effects of blank reagent and different solvents on the yield of benzil synthesized from benzoin were compared, and the results were shown in Table 1.

[0076] Table 1 Blank experiment and solvent effect a

[0077]

[0078]

[0079] a—reaction temperature 60°C, reaction time 2h

[0080] From 1,2 in Table 1, it can be seen that the oxidation effect is poor without FeNaEDTA and only H2O2 is used, and almost no product is produced with a small amount of H2O2, and benzoin is oxidized into benzoic acid under the action of excessive H2O2, and only a small amount of benzoin is produced; from 3,4, it can be seen that direct oxidation with FeNaEDTA has almost no oxidation effect with a small amount, and only when the amount of FeNaEDTA is 2-3 times that of benzoin, there is a certain oxidation effect, which is due to the direct oxidation effect of trivalent iron in FeNaEDTA, and the principle is similar to the action of directly using FeCl3·3H2O, obviously the oxidation efficiency is low, and the consumption of oxidant is large and the economic performance is poor; from 5,6, it can be seen that Fe Ⅲ Ⅲ in FeNaEDTA promotes the decomposition of H2O2, and the generated ·O2, ·O, ·OH free radicals and O2 molecules rapidly oxidize benzoin, and 1% TBAB as a phase transfer catalyst plays a catalytic effect; from 6,7,8,9, it can be seen that under the condition that other conditions are the same, the effect of solvents C2H5OH and DMF is good, but DMF as a solvent is heavily polluted and the post-treatment is troublesome, and the effect of H2O and CH3CN as solvents is not ideal, which may be related to the solubility of reactants in H2O and the small polarity of CH3CN.

[0081] The above is the method for synthesizing benzoin substances according to the present application, and it should be pointed out that the above-mentioned embodiments should not be regarded as a limitation of the present application, and the protection scope of the present application should be limited by the scope defined in the claims. For ordinary skilled persons in the technical field, several improvements and refinements can be made without departing from the spirit and scope of the present application, and these improvements and refinements should also be regarded as the protection scope of the present application.​

Claims

1. A method for synthesizing benzil or its derivatives from green guaiac or its derivatives, characterized by, The coordination compound synthesized by metal salt and disodium ethylenediaminetetraacetate is used as catalyst, H2O2 is used as oxidant, and TBAB is used as cocatalyst, and the compound 1 is oxidized into the compound 2 in ethanol solvent; ； R is any one of aryl and heteroaryl; aryl is selected from one of phenyl, naphthyl, phenanthryl and anthryl; heteroaryl is selected from one of pyrrolyl, furanyl, thienyl, pyrazolyl and imidazolyl; The metal salt used is iron salt.

2. The method for synthesizing benzil or its derivatives from green guaiac or its derivatives according to claim 1, wherein, The specific steps of the method are as follows: ​ (1) the coordination compound synthesized by metal salt and disodium ethylenediaminetetraacetate is used as catalyst; (2) compound 1 and catalyst are added into a reaction container, then ethanol and TBAB are added, H2O2 is added dropwise, magnetic stirring and oil bath heating are carried out, and the reaction product compound 2 is collected after the reaction is completed.

3. The method of synthesizing benzil or its derivatives from green guaiac or its derivatives according to claim 2, wherein, The reaction temperature is 20-100 DEG C.

4. The method of synthesizing benzil or its derivatives from green guaiac or its derivatives according to claim 2, characterized in that, The reaction time is 0.5-5 h.

5. The method of synthesizing benzil or its derivatives from green benzoine or its derivatives according to claim 2, wherein, The solvent used in the recrystallization after the reaction is one or more of water, methanol, ethanol, diethyl ether, acetonitrile and chloroform. ​ 6. The method of synthesizing benzil or its derivatives from green benzoine or its derivatives according to claim 1, wherein, When R of compound 1 is aryl, the dosage of hydrogen peroxide is 10-20 mL / 1 mmol benzoin; the dosage of catalyst is 0.1-0.20 g / 1 mmol benzoin; and the dosage of 1% TBAB is 5-10 mL / 1 mmol benzoin.

Images