CN1279128A - Process of preparing halobenzoic acid and its special composite catalyst - Google Patents

Abstract

The invention discloses a composite catalyst and a method for oxidizing halogenated toluene with general formula (I) to halogenated benzoic acid with general formula (II) by using the catalyst. The composite catalyst is composed of main catalyst and co-catalyst. Using halogenated toluene as raw material, in the presence of no solvent or a non-raw material solvent that does not participate in the oxidation reaction, using air as an oxidant, through a composite catalyst, the product halogenated benzoic acid is reacted at 80-200 ° C, and the yield is greater than 98%, and the purity is greater than 99%, so this process is particularly suitable for replacing the existing production process, and has important promotion value.

Description

Preparation method of halogenated benzoic acid and its special composite catalyst

The present invention relates to a method for preparing halogenated benzoic acid by using halogenated toluene and its special composite catalyst. It is a method for synthesizing halogenated benzoic acid through liquid-phase catalytic air oxidation of halogenated toluene under the condition of solvent or no solvent. Methods.

Halogenated benzoic acid is an important class of pharmaceutical, dye and pesticide intermediates. For example, p-chlorobenzoic acid is a synthetic broad-spectrum anthelmintic drug mebendazole (Pharmaceutical Industry, 1977, (2), 12) and flubendazole (Pharmaceutical Industry, 1983, (11) 1), a synthetic analgesic and anti-inflammatory drug indomethacin , acemetacin and oxametacin, etc. (Xiangtan Chemical Industry, Volume 24, Phase I); The raw material of Chuantong, anti-inflammatory spirit, antifungal drug clotrimazole, etc., can also be used to manufacture dyes and color films (Xiangtan Chemical Industry, Volume 24, Phase 1; Handbook of Fine Chemicals, Volume 1, P454, Science Press, 1992 Beijing); 2,4-dichlorobenzoic acid is the raw material for the synthesis of antimalarial drug aldipine hydrochloride and non-mercury diuretic furosemide (Handbook of Fine Chemicals, Volume 1, P643, Science Press, Beijing in 1992); 2 , 6-dichlorobenzoic acid is the raw material of synthetic acidic medium bleach B; p-fluorobenzoic acid is the raw material of synthetic anthelmintic (US4,605,757); o-bromobenzoic acid is the raw material of synthetic sweetener (US4, 605, 757) and so on. The preparation of the above halogenated benzoic acid mainly takes halogenated toluene as raw material and adopts an oxidation method to obtain it. Commonly used oxidizing agents mainly contain two classes, one is chemical oxidizing agents, such as potassium dichromate, potassium permanganate and nitric acid (CN1104626). Due to the high cost of using potassium dichromate and potassium permanganate as oxidants, a large amount of waste water containing heavy metal ions is discharged. At present, nitric _acid is widely used in industry. Waste water seriously pollutes the environment, and its application is strictly restricted by the national environmental protection department. Some manufacturers using this process have been shut down or replaced with other production processes. The other is to use air as an oxidant, use cobalt, iron, nickel, copper, molybdenum or manganese salts as a catalyst, and use a low-level aliphatic carboxylic acid with 2 to 3 carbons as a solvent to synthesize it by a one-step oxidation method under pressure (US4 , 605, 757; Khim-Farm. Zh. 1991, 25(1), 68-9; Zh. Prikl. Khim. (Leningrad) 1977, 50(1), 133-6; Jp58-32843). The disadvantage of this process is that the mother liquor cannot be directly recycled, the acetic acid is extremely corrosive, and the reaction equipment needs to be made of titanium steel, resulting in high production costs, serious environmental pollution, and poor labor sanitation conditions in the factory. Manufacturers of benzoic acid discontinued or changed production.

In order to overcome the above shortcomings, many people have carried out in-depth research on the preparation method of halobenzoic acid. For example, in a 1,2-dimethoxyethane solvent containing NaOH, crown ether is used as a catalyst, and halogenated toluene is oxidized with oxygen to synthesize halogenated benzoic acid (Tetrahedron Letter, Vol.25, No.43, 4989-4992), but the reaction rate is very slow, and the reaction rate is only about 20% in 5 hours; and the crown ether is expensive, a large amount of NaOH is difficult to reclaim, and the environmental pollution is large. Consider, this technology is impossible to realize industrialization; Use cobalt salt and 17-58 carbon quaternary ammonium salt as catalyst, do not need solvent, also can synthesize halogenated benzoic acid (US 4,990,659), but quaternary ammonium salt consumption is large , and the long-chain quaternary ammonium salt is expensive, resulting in high production costs, and is also not suitable for the production of halogenated benzoic acids.

The object of the present invention is to provide a kind of composite catalyst specially used for preparing halogenated benzoic acid and the method for preparing halogenated benzoic acid with this composite catalyst. Using this catalyst to prepare halogenated benzoic acid should have milder and safer reaction conditions, basically no environmental pollution and equipment corrosion, less catalyst consumption, and the cost is not higher than that of the prior art. It can be produced by setting up a set of production equipment A series of halogenated benzoic acid products.

The technical scheme adopted for realizing the above-mentioned purpose of the present invention is as follows:

The present invention includes a composite catalyst and a method for oxidizing halogenated toluene with general formula (I) to halogenated benzoic acid with general formula (II) by using the catalyst.

In the formula, _X1 and _X2 represent hydrogen or halogen (fluorine, chlorine or bromine, etc.) respectively, but at least one of them represents halogen.

The specific instructions are as follows:

1. Composite catalyst,

It consists of a main catalyst and a cocatalyst in a molar ratio of 0.01:1 to 2.5:1, and the best molar ratio is 0.15:1 to 2:1. The main catalyst is an inorganic acid salt or an organic acid salt of variable valence metal, or a mixture thereof; the cocatalyst is composed of elemental bromine or bromide and a polar compound without bromine. The ratio of the two is 0.01:1 to 1.5:1, preferably 0.05:1 to 1:1. The main catalyst is calculated by the number of moles of metal atoms, the elemental bromine or bromide in the co-catalyst is calculated by the number of moles of bromine atoms, and the number of moles of polar compounds not containing bromine is calculated.

The variable-valence metal is iron, cobalt, nickel, copper, vanadium, chromium or manganese and the like. Inorganic acid salts of variable-valence metals are fluoride, chloride, bromide, or nitrate. The organic acid salts of variable-valence metals are acetates, oxalates, benzoates, naphthenates, stearates, or oleates.

The bromide used as a cocatalyst is Br ₂ , NaBr, KBr, NH ₄ Br, MnBr ₂ ·4H ₂ O, CoBr ₂ ·6H ₂ O, CBr ₄ , CHBr ₂ CHBr ₂ or HBr, etc. The bromine-free polar compound as a cocatalyst is pyridine, acetylacetone or water (including crystal water). Adding a small amount of polar compounds can promote the dissolution and dispersion of the catalyst and shorten the induction period of the oxidation reaction. Generally speaking, water will reduce the reaction rate of liquid-phase catalytic air oxidation, but in the system used in the present invention, trace amounts of water can play a catalytic role.

Two, prepare the method for halogenated benzoic acid with above-mentioned composite catalyst:

It uses halogenated toluene as raw material, in the presence of no solvent or non-raw material solvent that does not participate in the oxidation reaction, 0.0001-0.05 mole of composite catalyst is added to each mole of raw material, and 0.25-2 5MPa air, react at 80-200°C for about 4 hours, separate and collect the product halobenzoic acid after cooling.

The total amount of catalyst used varies widely, usually 0.0001-0.05 mole of catalyst per mole of halogenated toluene, preferably 0.0015-0.025 mole.

The oxidizing agent used in the present invention is air, and its pressure is 0.25-2.5 MPa, preferably 0.6-1.5 MPa. Using air as an oxidant is cheaper, more convenient, and safer than pure oxygen.

Liquid-phase catalytic air oxidation is a heterogeneous reaction. In order to disperse the air evenly in the reactor, an air distributor should be installed at the bottom of the reactor and a suitable agitator should be equipped.

The oxidation reaction is a strong exothermic reaction, the air flow rate should match the heat dissipation capacity of the reactor, and at the same time, the oxygen content in the tail gas should be lower than 5% to ensure the oxidation reaction proceeds safely.

When practicing the present invention, the reaction temperature can vary between 80°C to 200°C, preferably 100°C to 160°C.

The method for isolating halobenzoic acid from the reaction mixture prepared by applying the present invention can be carried out by adopting conventional basic process operations according to the properties of the material. For example: distilling, filtering and then refining the filter cake, etc. Generally, the solubility of halogenated benzoic acid in raw materials or solvents is small, and the crude product of halogenated benzoic acid can be obtained by filtering. The mother liquor and the catalyst contained therein can be directly recycled, and a small amount of catalyst carried in the product can also be recycled and reused.

Compared with prior art, adopt catalyst provided by the present invention and method to prepare halogenated benzoic acid, oxidant is air, not only convenient, safe, but also greatly reduce the corrosion of reaction system to equipment and the degree of environmental pollution, used solvent and catalyst It is easy to recover and recycle, the yield of the obtained product is greater than 98%, and the purity is greater than 99%, so it is particularly suitable for replacing the existing production process and has important promotion value.

The technical scheme of the present invention will be further described below in conjunction with specific embodiments:

Example 1

Preparation of p-chlorobenzoic acid

189.75g (1.5mol) p-chlorotoluene, 0.3g (0.96mmol) cobalt naphthenate, 0.1g (0.51mmol) MnCl ₂ ·4H ₂ O, 0.2g (1.68mmol) KBr After mixing, put it into a 300ml stainless steel autoclave, control the stirring speed to 500 rpm, and when the temperature rises to 80°C, air is introduced, and the air flow is controlled by a stainless steel needle valve installed at the outlet of the autoclave, and the tail gas enters the tail gas condenser Recover a small amount of raw materials and then measure and discharge them through the rotameter. The flow rate should be less than 5% of the residual oxygen content in the tail gas, generally controlled at 200ml/min, the reaction pressure is 0.8MPa, and the reaction temperature is 125-130°C. After about 4 hours, the reaction mixture was cooled, separated, washed and dried to obtain p-chlorobenzoic acid. Calculated according to the reacted p-chlorotoluene, the yield was 98.7% and the purity was 99.1%.

Example 2

Preparation of o-chlorobenzoic acid

Mix 189.75g (1.5mol) o-chlorotoluene, 0.35g (1.12mmol) cobalt naphthenate, and 0.2g (0.7mmol) MnBr ₂ 4H ₂ O into a 300ml stainless steel autoclave, operate The steps are the same as in Example 1, except that the difference from Example 1 is that the reaction temperature is controlled at 130-135°C. After reacting for 4 hours, the reaction mixture was cooled, separated, washed and dried to obtain o-chlorobenzoic acid. Calculated according to the reacted o-chlorotoluene, the yield was 98.1%, and the purity was 99.5%.

Example 3

Preparation of 2,4-dichlorobenzoic acid

193.2g (1.2mol) 2,4-dichlorotoluene, 0.25g (1.05mmol) CoCl ₂ ·6H ₂ O, 0.35g (1.43mmol) Mn(C ₂ H ₃ O ₂ ) ₂ 4H ₂ O, 0.4g (3.36mmol) KBr were mixed and added to a 300ml stainless steel autoclave, the operation steps were the same as in Example 1, the air flow rate was controlled at 250ml/min, the temperature was 135°C-140°C, and the air pressure was 0.8MPa. After reacting for 4 hours, the reaction mixture was cooled, separated, washed and dried to obtain 2,4-dichlorobenzoic acid. Calculated according to the reacted 2,4-dichlorotoluene, the yield was 98.5%, and the purity was 99.3%. .

Example 4

Preparation of 2,6-dichlorobenzoic acid

193.2g (1.2mol) 2,6-dichlorotoluene, 0.5g (1.53mmol) CoBr ₂ ·6H ₂ O, 0.4g (2.02mmol) MnCl ₂ 4H ₂ O, 0.4g ( 3.88mmol) NaBr was mixed and added into a 300ml autoclave. The operation steps were the same as in Example 1. The reaction temperature was controlled at 140° C. and the air pressure was 0.8 MPa. After 4 hours of reaction, the reaction mixture was cooled, separated, washed, and dried to obtain 2. 6-dichlorobenzoic acid, yield 97.6%, purity 99.0%.

Example 5

Preparation of p-fluorobenzoic acid

198.2g (1.8mol) p-fluorotoluene, 0.3g (0.96mmol) Co (Ac) 2, 0.2g (0.82mmol) Mn (NO ₃ ) ₂ · 4H ₂ O, 0.2g ( 1.68mmol) KBr, after mixing, add in 300ml stainless steel autoclave, operation procedure is the same as embodiment 1, control reaction temperature 140 ℃, air pressure 0.8MPa, cool reaction mixture after reacting for 4 hours, separate, wash, dry to get final product Fluorobenzoic acid, calculated according to the reacted p-fluorotoluene, has a yield of 99.1% and a purity of 99.3%.

Example 6

Preparation of p-bromobenzoic acid

188.14g (1.1mol) p-bromotoluene, 0.4g (1.68mmol) CoCl ₂ 6H ₂ O, 0.35g (1.43mmol) Mn(C ₂ H ₃ O ₂ ) ₂ 4H ₂ O , 0.4g (3.36mmol) KBr is added in the 300ml stainless steel autoclave after mixing, operation method is the same as embodiment 1, 140 ℃ of control reaction temperature, reaction pressure 0.8MPa, the cooling reaction mixture after reaction 4 hours, separation, washing, After drying, p-bromobenzoic acid is obtained. Calculated according to the reacted p-bromotoluene, the yield is 96.5% and the purity is 99.1%.

Example 7

Preparation of p-chlorobenzoic acid

126.5g (1mol) p-chlorotoluene, 0.3g (0.96mmol) cobalt naphthenate, 0.35g (1.43mmol) Mn(C ₂ H ₃ O ₂ ) ₂ 4H ₂ O, 0.2g (1.68mmol) KBr and 78g (1mol) benzene are mixed evenly and then added in a 300ml autoclave. The operation steps are the same as in Example 1, and the reaction temperature is controlled at 130° C. to 135° C., until the oxygen content in the tail gas gradually rises to 16% to 17%. (It takes about 4 hours to react), the reaction mixture is cooled, separated, washed and dried to obtain p-chlorobenzoic acid. Yield 98.8%, purity 99.1%.

Claims (12)

1. A composite catalyst for the preparation of halogenated benzoic acid is characterized in that it is composed of a main catalyst and an auxiliary agent in a molar ratio of 0.02:1 to 2.5:1, and the main catalyst is a variable-valence metal inorganic acid salt Or one or a mixture of organic acid salts; the cocatalyst is simple bromine or bromide and polar compounds without bromine. 2. The composite catalyst according to claim 1, characterized in that said variable valence metal is iron, cobalt, nickel, copper, vanadium, chromium or manganese. 3. The composite catalyst according to claim 1, characterized in that the inorganic acid salt of the variable valence metal is fluoride, chloride, bromide or nitrate. 4. The composite catalyst according to claim 1, characterized in that the organic acid salt of the variable valence metal is acetate, oxalate, benzoate, naphthenate, stearate or oleate. 5. The composite catalyst according to claim 1, characterized in that the bromide as a cocatalyst is Br ₂ , NaBr, KBr, NH ₄ Br, MnBr ₂ 4H ₂ O, CoBr ₂ 6H ₂ O, CBr ₄ , CHBr ₂ CHBr ₂ or HBr. 6. Composite catalyst according to claim 1, characterized in that the bromine-free polar compound as cocatalyst is pyridine, acetylacetone or water. 7. The composite catalyst according to claim 1, characterized in that the molar ratio of the main catalyst to the cocatalyst is 0.15:1 to 2:1. 8. The composite catalyst according to claim 1, characterized in that the molar ratio of the bromide to the bromine-free polar compound in the cocatalyst is 0.05:1 to 1:1. 9. A method for preparing halogenated benzoic acid with the composite catalyst described in any one of claims 1～8, it is that the halogenated toluene of general formula (I) is oxidized into the halogenated benzene of general formula (II) formic acid,

In the formula, _X1 and _X2 represent hydrogen or halogen (fluorine, chlorine or bromine etc.) respectively, but wherein at least one represents halogen, with halogenated toluene as raw material, it is characterized in that: in solvent-free or have not participate in oxidation reaction In the presence of non-raw material solvents, add 0.0001-0.05 moles of composite catalyst to each mole of raw materials, pass through 0.25-2.5Mpa of air, react at 80-200°C for about 4 hours, and separate after cooling The product halobenzoic acid was collected. 10. The method according to claim 9, characterized in that the molar ratio of the raw material to the composite catalyst is 1:0.0015 to 1:0.02. 11. The method according to claim 9, characterized in that the non-raw material solvent is one or a mixture of carbon tetrachloride, benzene, nitrobenzene, fluorobenzene or polyfluorobenzene. 12. The method according to claim 9, characterized in that the preferred reaction temperature is 100-160°C.