Tetramisole hcl is a white crystalline powder, which is a kind of imidazole compound. It has a wide range of pharmacological effects, including anti-inflammatory, analgesic, hypoglycemic and immunomodulatory effects in vivo. 2-Chloropropionyl chloride is a colorless liquid and an organic compound that is often used in the synthesis of various pesticides, drugs and dyes.
The first method: Condensation of chloroacetate with imidazole and formaldehyde using high pressure method:
The method adopts high-pressure conditions (80-100 MPa) to prepare an intermediate through the condensation reaction of chloroacetate, imidazole and formaldehyde, and then adds tetrabutylammonium bromide in the presence of hydrochloric acid to finally obtain the product tetramisole hcl.
The reaction steps are as follows:
1) Preparation of chloroacetate:
First, add chloroacetic acid and excess formaldehyde into an organic solvent, such as methanol or ethanol, and stir at room temperature. NaOH was added to bring the pH of the reaction solution close to 7.
Then, using a high-pressure reactor, the reaction was carried out under the reaction conditions of 160°C. The final product is chloroacetic formaldehyde carboxylate with the structure OHC(CH2)2Cl.
2) Preparation of imidazole:
In a reaction kettle, dissolve methyl ethyl ketone in alcohol solution, add chloroformamide and copper chloride, and stir at room temperature. Acetylimidazole was then added to the reaction mixture and reacted while heating to 70°C. The reaction mixture can be reacted at a high temperature of 90° C., and the reaction time is about 24 hours. The final product obtained is an imidazole compound with a structure of isoimidazolone, namely 2-(1H-imidazol-1-yl)acetophenone.
3) Condensation reaction of imidazole and chloroacetic acid formaldehyde carboxylate:
Imidazole was dissolved in methanol, and chloroacetic formaldehyde carboxylate was added thereto for mixing. The reactants are reacted at a high temperature of 160°C and pressurized in the reactor to ensure complete reaction of the reactants. The reaction time is 2 hours. The product produced by the condensation reaction is N-(2-oxo-5,5-dimethyl-1,3,2-imidazolyl)-chloroacetic acid formaldehyde amide with molecular formula C13H16N3O3Cl.
This intermediate still requires hydrochlorination to form tetramisole hcl. The above-mentioned intermediate is treated with an acid containing chloride ions, and tetrabutylammonium bromide is added for high-pressure hydrochlorination to finally obtain the product Tetramisole Hcl.
The preparation of Tetramisole Hcl intermediate requires the use of high-pressure reactors, and the reaction conditions involve high temperature and high pressure. Careful and precise control of the reaction conditions is required to ensure complete reaction of the reactants. In a series of complex chemical processes, the intermediate N-(2-oxo-5,5-dimethyl-1,3,2-imidazolyl)-chloroacetic acid formaldehyde amide is crucial in the preparation of Tetramisole Hcl important step.
Advantages: simple separation and purification of reaction products, high yield.
Disadvantages: This method requires a high-pressure environment, and the operation is more dangerous.
The second method: reaction of imidazole acetone, benzoic acid and carboxylic acid derivatives:
The main step of the method is to react imidazole acetone, benzoic acid and carboxylic acid derivatives to form a four-membered heterocycle. Subsequently, reduction of the four-membered heterocycle affords TH.
Tetramisole hcl Inclusions is a widely used insect repellent for livestock and it is also used in the medical field. Imidazole acetone, benzoic acid and carboxylic acid are derivatives of Tetramisole Hcl, which are all organic compounds. The reactions and detailed procedures of imidazole acetone, benzoic acid and carboxylic acid derivatives of Tetramisole Hcl derivatives are described below.
1. Reaction of imidazole acetone derivatives:
Imidazole acetone derivatives are weakly basic compounds that can react with acids to form salts. Following is the reaction and detailed steps of imidazole acetone derivatives:
1.1 React with sulfuric acid:
Imidazole acetone derivatives can react with sulfuric acid to form salts, and this reaction is usually used in the preparation of Tetramisole Hcl derivatives. The reaction equation is as follows:
R-CH=N-CH3 + H2SO4 → R-CH=N-CH3·H2SO4
Among them, R-CH=N-CH3 represents imidazole acetone derivatives.
The reaction steps are as follows:
1) Mix the imidazole acetone derivative and concentrated sulfuric acid.
2) Stir the mixture so that it is evenly combined.
3) After the reaction, rinse with ice water and filter the solid to obtain imidazole acetone sulfate.
1.2 Reaction with aldehydes:
Imidazoleacetone derivatives can react with aldehydes to form imidazoleacetone aldimines. The reaction equation is as follows:
R-CH=N-CH3 + R'CHO → R-CH=N-CH3CHO
Among them, R-CH=N-CH3 represents imidazole acetone derivative, R'CHO represents aldehyde.
The reaction steps are as follows:
1) Mix imidazole acetone derivative and aldehyde.
2) In the presence of ethanol and anhydrous sodium hydroxide solution, the reaction is catalyzed.
3) After the reaction, rinse with ice water and filter the solid to obtain imidazole acetone aldimine.
2. Benzoic acid derivative reaction:
Benzoic acid derivatives are unstable compounds that can form more stable compounds through a variety of reactions. Following is the reaction and detailed steps of benzoic acid derivative:
2.1 Elemental analysis:
Benzoic acid derivatives can be detected by elemental analysis. The test substance will react with chemical reagents to generate gas, and then the gas will enter the elemental analyzer for detection. The reaction equation is as follows:
C7H7O2 + O2 → CO2 + H2O
The detection steps are as follows:
1) Put the benzoic acid derivative into a pre-weighed combustion flask.
2) Add solid oxidizer (such as copper oxide) and mix well.
3) Use a lamp to burn the oxygen-absorbing cotton at the bottom of the bottle and ignite the reaction mixture.
4) Put the gas into the elemental analyzer for detection.
2.2 Reaction with sodium nitrite:
Benzoic acid derivatives can react with sodium nitrite to produce benzimidazoles. The reaction equation is as follows:
C7H7O2 + NaNO2 + HCl → C11H8N2 + NaCl + 2H2O
Among them, C7H7O2 represents benzoic acid derivative, and C11H8N2 represents benzimidazole.
The reaction steps are as follows:
1) Dissolve the benzoic acid derivative in concentrated hydrochloric acid.
2) Add sodium nitrite solution and stir to mix.
3) React at room temperature for 6-8 hours.
4) After the reaction, add sodium hydroxide solution to adjust the pH value to 7.
5) Wash with ethanol, filter the solid to obtain benzimidazole.
3. Reaction of carboxylic acid derivatives:
Carboxylic acid derivatives are a class of widely used compounds that can form other organic compounds through various reactions. The following are the reactions and detailed steps of carboxylic acid derivatives:
3.1 Addition reaction:
Carboxylic acid derivatives can undergo addition reaction with double bond compounds to generate allyl carboxylic acid derivatives. The reaction equation is as follows:
R-COOH + H2C=CH-CN → R-COOCH=CHCH2CN
Among them, R-COOH represents a carboxylic acid derivative, and H2C=CH-CN represents a double bond compound.
The reaction steps are as follows:
1) Mix carboxylic acid derivative and double bond compound.
2) Add catalyst (such as aluminum trichloride) and mix well.
3) Bubble nitrogen and stir the mixture.
4) React for several hours at room temperature.
5) After the reaction, rinse with cold water and filter the solid to obtain allyl carboxylic acid derivatives.
3.2 Carbonylation reaction:
Carboxylic acid derivatives can form carbonyl compounds through carbonylation reactions. The reaction equation is as follows:
R-COOH + (COCl)2 → R-COCl + CO2 + HCl
Among them, R-COOH represents a carboxylic acid derivative, and (COCl)2 represents carbonyl chloride.
The reaction steps are as follows:
1) A carboxylic acid derivative and carbonyl chloride are mixed.
2) Add cocatalyst (such as dichloromethane) and mix well.
3) React for several hours at low temperature.
4) After the reaction is over, add the reactant into ice water, stir and cool, and add sodium hydroxide solution to neutralize.
5) Wash with ether and filter the solid to obtain the carbonyl compound.
In summary, the imidazolacetone, benzoic acid, and carboxylic acid derivatives of Tetramisole Hcl are organic compounds that can all produce other organic compounds through a variety of reactions. Different reactions require different reaction steps to obtain expected products.
Advantages: low production cost and easy purification of reaction products.
Disadvantages: The reaction conditions are harsh and the yield is low.