A method for preparing heterocyclic aromatic amides by hydrolysis of heterocyclic aromatic nitriles with vanadium catalyst

Abstract

The application provides a method for preparing a heterocyclic aromatic amide by hydrolyzing a heterocyclic aromatic nitrile with a vanadium catalyst, and belongs to the technical field of fine chemicals. The method is a new method for preparing a heterocyclic aromatic amide by hydrolyzing a heterocyclic aromatic nitrile as a raw material with a vanadium-based material as a catalyst. The vanadium-based material is prepared by mixing amine groups in an organic amine and vanadium substances in an inorganic vanadium compound at a mass ratio of 1:1-1:6, calcining under the condition of 300-1000 DEG C in an inert atmosphere for 0.5-20 h, and cooling, and can efficiently catalyze the hydrolysis of a heterocyclic aromatic nitrile into a corresponding amide. The method has the advantages of mild reaction conditions, few by-products, and easy separation of the catalyst and the product from the reaction system, and has strong practicability and broad application prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of fine chemicals, and particularly relates to a new method for preparing heterocyclic aromatic amides by hydrolysis reaction using heterocyclic aromatic nitrile as raw material and vanadium-based material as catalyst. BACKGROUND

[0002] Heterocyclic aromatic amides have important applications in the fields of medicine, materials and fine chemical synthesis, etc., and the hydrolysis of heterocyclic aromatic nitrile is one of the important ways to prepare amides. For example, pyrazine amide can be used in combination with isoniazid, ethambutol and rifampicin to treat tuberculosis, which is usually prepared by hydrolysis of 2-cyanopyrazine. Nicotinamide can be used to prevent and treat pellagra, stomatitis, glossitis, etc., and can also be used as a whitening ingredient in daily chemical products, which is usually prepared by hydrolysis of 3-cyanopyridine. Therefore, it is of great significance to study the hydrolysis of heterocyclic aromatic nitrile to amide.

[0003] Traditional catalytic nitrile hydrolysis mainly uses strong acid and strong base catalysts, including H2SO4 or NaOH, etc. This process is easy to cause excessive hydrolysis to generate carboxylic acid, and the neutralization of catalyst after reaction will generate waste residue. Transition metal-catalyzed nitrile hydrolysis reaction can be carried out under neutral conditions, and has good development prospects. For example, the palladium complex prepared by Mizuno et al. using Pd(OAc)2 and TBA4[γ-SiW 10 O 34 (H2O)2] can efficiently catalyze the hydrolysis reaction of nitrile compounds with various structures such as aromatic and aliphatic (J. Am. Chem. Soc., 2012, 134, 6425-6433); Chinese invention patent (CN104744288A) catalyzes the hydrolysis of nitrile to amide by using rhodium complex. Homogeneous catalysts are difficult to separate from products, and metal impurities are easy to contaminate products. From the practical and environmental friendly point of view, it is of great significance to develop heterogeneous catalysts for nitrile hydrolysis to prepare amides. For example, Shimizu et al. found that metal oxide CeO2 can catalyze the hydrolysis reaction of nitrile compounds with heteroatoms, and the research results also showed that only when the heteroatom (N or O) in the heterocyclic compound is connected to the α-carbon adjacent to the cyano group, the heterocyclic aromatic nitrile compound can be efficiently hydrated to convert into the corresponding amide, and the aromatic or aliphatic nitrile compounds without heteroatoms hardly react (Chem. Eur. J., 2011, 17, 11428-11431); Chinese invention patent (CN101277762B) uses manganese dioxide catalyst added with lanthanide elements (alkali metals) to catalyze the hydrolysis of nitrile to amide. These methods have their own advantages and disadvantages, and it is still of great application value to develop new methods for preparing heterocyclic aromatic amides which are cheap, efficient and environmentally friendly.

[0004] The present application uses vanadium-based material as catalyst to hydrolyze heterocyclic aromatic nitrile into corresponding amide, and has mild reaction condition, simple catalyst and product separation and less by-products. SUMMARY

[0005] The present application provides a new method for catalyzing heterocyclic aromatic nitrile hydrolysis to prepare amide. The method is a new method for preparing heterocyclic aromatic amide by one-pot method through hydrolysis reaction using heterocyclic aromatic nitrile as raw material and vanadium-based material as catalyst.

[0006] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0007] A method for preparing heterocyclic aromatic amide by vanadium catalyzed heterocyclic aromatic nitrile hydrolysis, which hydrolyzes heterocyclic aromatic nitrile into amide using vanadium-based material as catalyst, and comprises the following steps:

[0008] First step, preparation of catalyst

[0009] After mixing inorganic vanadium compound with organic amine, the mixture is calcined in inert atmosphere at 300-1000℃ for 0.5-20h and then cooled to obtain vanadium-based material. The molar ratio of amine group in organic amine to vanadium substance in inorganic vanadium compound is 1:1-1:6.

[0010] Second step, preparation of heterocyclic aromatic amide

[0011] Heterocyclic aromatic nitrile, water, catalyst and organic solvent are added into a reactor, and the mixture is stirred and heated to 50-150℃ for hydrolysis reaction, and the reaction time is 0.5-48h to obtain corresponding amide compound. In the hydrolysis reaction, the amount of water is 1.1-100 times of the amount of substance of raw material heterocyclic aromatic nitrile; the volume ratio of organic solvent to water is 0-5, wherein 0 means no organic solvent is added, and the added organic solvent is to increase the solubility of raw material; and the amount of catalyst is 1-40wt% of the amount of raw material heterocyclic aromatic nitrile.

[0012] The heterocyclic aromatic nitrile is one or more mixture of structure formula I, II, III, IV, V or VI.

[0013]

[0014] The heterocyclic aromatic nitrile is in the alpha position, beta position or gamma position of the cyano group in the structure of I, II, III, IV, V or VI.

[0015] Further, the mixing method in the first step is mixing in water or an organic solvent or direct mechanical grinding mixing.

[0016] Further, the inorganic vanadium compound in the first step is one or more of vanadyl sulfate, ammonium metavanadate, sodium metavanadate, vanadium dioxide, divanadium trioxide and divanadium pentoxide, and the organic amine is one or more of polyaniline, diethylene diamine and melamine.

[0017] Further, the inert atmosphere in the first step is one or more of nitrogen and argon.

[0018] Further, the reactor in the second step is an open container or a closed reaction kettle.

[0019] Further, the hydrolysis reaction atmosphere in the second step can be one or more of air and nitrogen.

[0020] Further, the organic solvent in the second step is one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, acetonitrile and 1,4-dioxane.

[0021] The reaction principle of the present application is as follows:

[0022]

[0023] The present application has the following beneficial effects:

[0024] The present application provides a new method for preparing amides by hydrolysis of vanadium-catalyzed heterocyclic aromatic nitriles. The method uses vanadium-based materials as catalysts to efficiently catalyze the hydrolysis of heterocyclic aromatic nitriles into corresponding amides. The reaction conditions are mild, safe and environmentally friendly, the by-products are few, and the separation of the catalyst from the product is simple, which has strong practicability and broad application prospect. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 is the GC spectrum of Example 1, which is the hydrolysis of 2-cyanopyrazine to prepare pyrazine amide.

[0026] Figure 2Example 2 is the preparation of 2-pyrazinecarboxamide by hydrolysis of 2-cyanopyrazine 1 H NMR spectrum. DETAILED DESCRIPTION

[0027] The technical solutions of the present application are described in detail below through examples, but the protection scope of the present application is not limited thereto.

[0028] Example 1: Preparation of catalyst A and reaction results

[0029] The vanadium-based material was prepared by using melamine and ammonium metavanadate (1:3) in terms of the amount of substance: 1.0 g of melamine and 2.8 g of ammonium metavanadate powder were taken into a mortar for solid-phase mechanical grinding, and the obtained powder was loaded into a porcelain boat for calcination in a tube furnace under a nitrogen atmosphere at 600°C with a heating rate of 10°C / min, and after being kept at constant temperature for 1.5 h, it was cooled to room temperature under a nitrogen atmosphere to obtain a vanadium-based material solid powder, which was recorded as catalyst A.

[0030] 2 mmol of 2-cyanopyrazine, 20 wt% of catalyst, and 3 mL of H2O were added into a round-bottom flask equipped with a condenser for refluxing, and the temperature was raised to 100°C, and after 6 h of reaction, the aqueous solution after reaction was extracted with CH2Cl2, and the extracted solution was collected, and qualitative analysis of the reaction product was performed by using a gas chromatography-mass spectrometry instrument (GC-MS), and quantitative analysis of the reaction product was performed by using a gas chromatography (GC), and the conversion rate of the reaction substrate and the selectivity of the product were calculated by the area normalization method. The conversion rate of 2-cyanopyrazine was 90%, and the selectivity of 2-pyrazinecarboxamide was greater than 99%, and the reaction results are shown in Table 1, and the conversion rate of the raw material and the selectivity of the product in Examples 3-8 below were calculated by using this method.

[0031] Example 2: Except that the reaction time was extended to 12 h, the other experimental methods were the same as in Example 1, and the results were analyzed. The conversion rate of 2-cyanopyrazine was 99%, and the selectivity of 2-pyrazinecarboxamide was greater than 99%. The separation experiment of the hydrolysis product 2-pyrazinecarboxamide was performed in the following steps: after the 2-cyanopyrazine hydrolysis reaction was completed, the aqueous solution after reaction was first extracted with CH2Cl2, and then CH2Cl2 was removed by rotary evaporation, and after vacuum drying, a white solid was obtained, and 2-pyrazinecarboxamide was directly separated 1 H NMR diagram, Figure 2 , 1 H NMR (500 MHz, DMSO-d6) δ: 9.19 (s, 1H), 8.72-8.86 (d, J = 69.0 Hz, 2H), 8.28 (s, 1H), 7.88 (s, 1H).

[0032] Example 3: Preparation of catalyst B and reaction results

[0033] Vanadium-based material preparation process using the amount of melamine and vanadium dioxide (1:2) preparation: 1.0 g of melamine and 1.3 g of vanadium dioxide powder into a mortar for solid-phase mechanical grinding, the resulting powder with porcelain boat loading calcination, in a nitrogen atmosphere, 650 ℃ in a tube furnace, the heating rate 5 ℃ / min, constant temperature 3 h after the nitrogen atmosphere to room temperature, the vanadium-based material solid powder, recorded as catalyst B.

[0034] 2 mmol of 2-cyanopyridine, 40 wt% catalyst B, 0.5 mL of water and 1 mL of ethanol into a closed reaction kettle with nitrogen, heated to 150 ℃, reaction 0.5 h. The conversion of 2-cyanopyridine is 99%, the selectivity of 2-pyridine carboxamide is greater than 99%, and the reaction results are shown in Table 1.

[0035] Example 4: Preparation of C catalyst and reaction results

[0036] Vanadium-based material preparation process using the amount of melamine and vanadium dioxide (1:2) preparation: 1.0 g of melamine and 1.3 g of vanadium dioxide powder into a mortar for solid-phase mechanical grinding, the resulting powder with porcelain boat loading calcination, in a nitrogen atmosphere, 650 ℃ in a tube furnace, the heating rate 5 ℃ / min, constant temperature 3 h after the nitrogen atmosphere to room temperature, the vanadium-based material solid powder, recorded as catalyst B.

[0037] 50 mmol of 2-cyanofuran, 10 wt% of catalyst C, 1 mL of water and 1 mL of ethanol into a conical flask with nitrogen, heated to 50 ℃, reaction 48 h. The conversion of 2-cyanofuran is 95%, the selectivity of 2-furanamide is greater than 99%, and the reaction results are shown in Table 1.

[0038] Example 5: Preparation of D catalyst and reaction results

[0039] Vanadium-based material preparation process using the amount of melamine and vanadium dioxide (1:2) preparation: 1.0 g of melamine and 1.3 g of vanadium dioxide powder into a mortar for solid-phase mechanical grinding, the resulting powder with porcelain boat loading calcination, in a nitrogen atmosphere, 650 ℃ in a tube furnace, the heating rate 5 ℃ / min, constant temperature 3 h after the nitrogen atmosphere to room temperature, the vanadium-based material solid powder, recorded as catalyst B.

[0040] 20 mmol of 3-cyanothiophene, 5 wt% of catalyst D, 2 mL of water, 1 mL of ethanol and 1 mL of n-propanol into a round-bottom flask with a condenser, heated to 60 ℃, reaction 36 h. The conversion of 3-cyanothiophene is 91%, the selectivity of 3-thiopheneamide is greater than 99%, and the reaction results are shown in Table 1.

[0041] Example 6: Preparation of catalyst E and reaction results

[0042] Vanadium-based material was prepared by using melamine, diethylene diamine and vanadyl sulfate with a molar ratio of 1:1:2: 1.0 g of melamine, 0.7 g of diethylene diamine and 2.6 g of vanadyl sulfate powder were added into a mixed solution of isopropyl alcohol and methanol, and then mixed thoroughly. The obtained powder was loaded into a porcelain boat and calcined in a tube furnace under an argon atmosphere at 800 °C with a heating rate of 5 °C / min. After being kept at a constant temperature for 5 h, the temperature was decreased to room temperature under an argon atmosphere. Vanadium-based material solid powder was obtained and was recorded as catalyst E.

[0043] 10 mmol of 4-cyanopyridine, 10 wt% of catalyst E, 2 mL of water and 1 mL of n-propanol were added into a closed reaction kettle with nitrogen flowing. The temperature was increased to 100 °C and the reaction was carried out for 24 h. The conversion of 4-cyanopyridine was 93% and the selectivity of 4-pyridinecarboxamide was more than 99%. The reaction results are shown in Table 1.

[0044] Example 7: Preparation of catalyst F and reaction results

[0045] Vanadium-based material was prepared by using polyaniline and vanadium dioxide with a molar ratio of 1:2: 1.0 g of polyaniline and 1.8 g of vanadium dioxide powder were added into a mortar and mechanically ground. The obtained powder was loaded into a porcelain boat and calcined in a tube furnace under an argon atmosphere at 700 °C with a heating rate of 10 °C / min. After being kept at a constant temperature for 10 h, the temperature was decreased to room temperature under an argon atmosphere. Vanadium-based material solid powder was obtained and was recorded as catalyst F.

[0046] 2 mmol of 2,3-dicyanopyrazine, 30 wt% of catalyst F, 1 mL of water and 5 mL of methanol were added into a round-bottom flask with a condenser. The temperature was increased to 60 °C and the reaction was carried out for 48 h. The conversion of 2,3-dicyanopyrazine was 90% and the selectivity of 2,3-dipyrazinecarboxamide was more than 99%. The reaction results are shown in Table 1.

[0047] Example 8: Preparation of catalyst G and reaction results

[0048] Vanadium-based material was prepared by using polyaniline and vanadium pentoxide with a molar ratio of 1:4: 1.0 g of polyaniline and 5.2 g of vanadium pentoxide powder were added into a mixed solution of n-propanol and ethanol. The obtained powder was loaded into a porcelain boat and calcined in a tube furnace under an argon atmosphere at 400 °C with a heating rate of 10 °C / min. After being kept at a constant temperature for 4 h, the temperature was decreased to room temperature under an argon atmosphere. Vanadium-based material solid powder was obtained and was recorded as catalyst G.

[0049] Into a sealed autoclave reactor, 10 mmol of 2-chloro-5-cyanothiophene, 20 wt% of catalyst G, 3 mL of water and 1 mL of isopropanol were charged, and the temperature was raised to 80 °C. The reaction was carried out for 16 h. The conversion of 2-chloro-5-cyanothiophene was 94%, and the selectivity of 2-chloro-5-thiopheneamide was more than 99%. The results of the reaction are shown in Table 1.

[0050] The above-described examples only express the embodiments of the present application, but cannot be understood as limiting the scope of the patent of the present application. It should be noted that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application.

[0051] Table 1. Different catalysts and corresponding reaction results

[0052] No. Catalyst (mol / mol) Conversion rate (%) Selectivity (%) A Melamine: ammonium metavanadate = 1 :3 90 >99 B Melamine: vanadium dioxide = 1 :2 99 >99 C Diethylenediamine: vanadium trioxide = 1 :4 95 >99 D Diethylenediamine: sodium metavanadate = 1 :6 91 >99 E Melamine: diethylenediamine: vanadyl sulfate = 1 : 1 :2 93 >99 F Polyaniline: vanadium dioxide = 1 :2 90 >99 G Polyaniline: vanadium pentoxide = 1 :4 94 >99

Claims

1. A process for the hydrolysis of heteroaromatic nitriles to heteroaromatic amides catalyzed by vanadium, characterized in that, The method is to hydrolyze heterocyclic aromatic nitrile into amide by using vanadium-based material as catalyst, The method comprises the following steps: Step 1, preparation of catalyst After mixing the inorganic vanadium compound with the organic amine, the mixture is calcined in an inert atmosphere at a temperature of 300-1000 DEG C for 0.5-20 h and then cooled to obtain the vanadium-based material; the molar ratio of the amine group in the organic amine to the vanadium substance in the inorganic vanadium compound is 1:1-1:6; The inorganic vanadium compound is one or more of vanadyl sulfate, ammonium metavanadate, sodium metavanadate, vanadium dioxide, divanadium trioxide and divanadium pentoxide; the organic amine is one or more of polyaniline, diethylene diamine and melamine; Step 2, preparation of heterocyclic aromatic amide In the reactor, heterocyclic aromatic nitrile, water, catalyst and organic solvent are added, and the mixture is stirred and heated to 50-150 DEG C to perform hydrolysis reaction, and the reaction time is 0.5-48 h, and the corresponding amide compound is separated; in the hydrolysis reaction, the amount of water is 1.1-100 times the amount of substance of the raw material heterocyclic aromatic nitrile; the volume ratio of the organic solvent to water is 0-5; the amount of catalyst is 1-40 wt% of the amount of the raw material heterocyclic aromatic nitrile; The heterocyclic aromatic nitrile is one or more of the mixtures of structures I, II, III, IV, V or VI; ； Ⅰ Ⅱ Ⅲ ； Ⅳ Ⅴ Ⅵ In the formula, the heteroatom X is N, O and S element, and the corresponding heterocyclic compounds are furan, pyrrole and thiophene, the substituent group R is one or more than two combinations of H, alkyl, phenyl, halogen, nitro, cyano, amino, methoxy, ethoxy, acetylamino or acetoxy, the number of R is one or more than one, and the position of R is one or more of ortho, meta or para; R is H, which means that the heterocyclic ring only has cyano.

2. The process for the hydrolysis of heteroaromatic nitrile to heteroaromatic amide using vanadium catalyst as claimed in claim 1, wherein, In step 1, the mixing method is mixing in water or organic solvent or direct mechanical grinding mixing.

3. The process for the hydrolysis of heteroaromatic nitrile to heteroaromatic amide using vanadium catalyst as claimed in claim 1, wherein, In step 2, the hydrolysis reaction atmosphere can be air, nitrogen or a mixture of one or more thereof.

4. The process for the hydrolysis of heteroaromatic nitrile to heteroaromatic amide using vanadium catalyst as claimed in claim 1, wherein, In step 2, the organic solvent is one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, acetonitrile, 1,4-dioxane.

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