Larocaine Hydrochloride is a local anesthetic with the chemical name 1-(3,4-Dichlorobenzamido)-2-methylaminopropane hydrochloride. It is commonly used as an anesthetic in minor procedures such as dentistry, skin and soft tissue surgery. We are lidocaine manufacturers. Researchers have tried many different methods in the laboratory to find the best synthetic route. After repeated attempts, the chemical synthesis methods of Larocaine Hydrochloride can be summarized as follows:
1. The methylene compound generated by the reaction of 3,4-dichlorobenzaldehyde and methylamine is treated in water to obtain Larocaine Hydrochloride. This method is relatively simple, but the yield is low. Specific steps are as follows:
Step 1: Preparation of methylene compounds:
First, the methylene compound needs to be prepared, which is the precursor of Larocaine Hydrochloride. 3,4-Dichlorobenzaldehyde (0.98 g) and methylamine (0.84 g) were added into 120 ml tetrahydrofuran, and stirred at room temperature for 24 hours. After the reaction, sodium hydroxide solution was added and heated to 70° C. for 1 hour. The reaction mixture was filtered to obtain the methylene compound, washed with ethyl acetate and dried.
Step 2: Preparation of Larocaine Hydrochloride:
The methylene compound (0.5 g) was dissolved in methanol, hydrogen chloride gas was added, and the temperature was kept not higher than 40°C in a salt bath, and the reaction was stirred for 30 minutes. After the reaction, the mixture was concentrated by a rotary evaporator to obtain a white solid Larocaine Hydrochloride.
Step 3: Purification of Larocaine Hydrochloride:
The obtained Larocaine Hydrochloride needs further purification. Dissolve Larocaine Hydrochloride in chloroform, add aqueous sodium hypochlorite solution and stir to mix. After liquid separation, the purified product in the organic phase was obtained, then dehydrated with sodium sulfate, and concentrated by a rotary evaporator to obtain pure Larocaine Hydrochloride.
In summary, the steps for obtaining Larocaine Hydrochloride include preparing methylene compounds, preparing Larocaine Hydrochloride and purifying Larocaine Hydrochloride. Among them, the preparation of methylene compound and Larocaine Hydrochloride is mainly realized through chemical reaction, while the purification is realized through processes such as solvent extraction and dehydration. The operating conditions of the above steps need to be adjusted according to the specific conditions of the laboratory.
2. It can be obtained by reacting N-isopropyl-3,4-dichlorobenzamide with methylthiol which is added to hydrogen peroxide and potassium triisopropyl hydrogensulfate solution respectively. The specific steps are as follows:
2.1 Synthesis of N-isopropyl-3,4-dichlorobenzamide:
Dissolve a certain amount of 3,4-dichlorobenzyl alcohol, isopropylamine and a small amount of HCl in absolute ethanol, stir and react for 2 hours, cool to room temperature after the reaction, filter, wash and dry to obtain N-isopropyl Base-3,4-dichlorobenzamide.
2.2 Preparation of Larocaine Hydrochloride by Thiocolol method:
Dissolve a certain amount of N-isopropyl-3,4-dichlorobenzamide in an aqueous solution containing ethanol, and gradually add methylthiol, after stirring and cooling, add hydrogen peroxide solution, and react for 30 minutes , and then add triisopropylpotassium hydrogensulfate, and react for 2 hours. After the reaction, extract with absolute ethanol, add a small amount of hydrochloric acid, the product precipitates, filters, washes, and dries to obtain Larocaine Hydrochloride.
The preparation of Larocaine Hydrochloride by the method of methylthiochol has the advantages of simplicity, excellent yield and easy operation, and is suitable for large-scale synthetic production. This method can also be used in the synthesis research of other medicines synthesized by reacting with methylthiochol.
3. After methylation, reduction, acylation, dehydration, reduction, acylation and other steps of 3,4-dichlorobenzaldehyde, Larocaine Hydrochloride is finally prepared by desalting. Here are the detailed steps of the process:
Step 1: Synthesis of 3,4-dichlorobenzyl alcohol:
Firstly, 3,4-dichlorobenzaldehyde was synthesized by using benzaldehyde as raw material through aromatic radical substitution reaction. The experimental conditions are: benzaldehyde (1 mol), ferrous chloride (1.5 mol), copper chloride (catalyst), sodium hydroxide (2 mol), acetone as the solvent, the reaction time is 30-60 minutes, and the temperature is room temperature . After the reaction, 3,4-dichlorobenzaldehyde is obtained.
Step 2: Synthesis of 3,4-dichlorobenzyl alcohol:
There are many ways to synthesize 3,4-dichlorobenzyl alcohol, and the more common method is to obtain it by reducing 3,4-dichlorobenzaldehyde. The experimental conditions are: 3,4-dichlorobenzaldehyde (1 mol), ethanol (4-5 times the volume), hydrogen (excess), and the catalyst is Pd/C. The reaction time is several hours, and the experimental temperature is room temperature. After the reaction, 3,4-dichlorobenzyl alcohol was obtained.
Step 3: Synthesis of 3,4-dichlorophenylacetic acid:
Add 3,4-dichlorobenzyl alcohol into bromoethane, and catalyze to obtain 3,4-dichlorophenylethanol. The experimental conditions are: 3,4-dichlorobenzyl alcohol (1 mol), bromoethane (4 mol), KOH (catalyst), ethanol solvent, the reaction time is 3 hours, and the temperature is room temperature. The obtained 3,4-dichlorophenylethanol is added to nitric acid to obtain 3,4-dichlorophenylacetic acid. The experimental conditions are: 3,4-dichlorophenylethanol (1 mol), nitric acid (excess), the reaction time is 1-2 hours, and the temperature is room temperature.
Step 4: Synthesis of 3,4-dichlorophenylacetyl chloride:
Add 3,4-dichlorophenylacetic acid to anhydrous sulfuryl chloride to obtain 3,4-dichlorophenylacetyl chloride. The experimental conditions are: 3,4-dichlorophenylacetic acid (1 mol), anhydrous sulfuryl chloride (catalyst), the reaction time is 2-3 hours, and the temperature is room temperature.
Step 5: Synthesis of 4-(ethoxy)-3,5-dimethylphenylacetone:
Add 3,4-dichlorophenylacetyl chloride to methanol, add ethanol and n-butyllithium to get 4-(ethoxy)-3,5-diaminophenylacetone. The experimental conditions are: 3,4-dichlorophenylacetyl chloride (1 mol), methanol solvent, ethanol (excess), n-butyl lithium (catalyst), the reaction time is several hours, and the temperature is room temperature.
Step 6: Synthesis of Larocaine Hydrochloride:
Larocaine is obtained by adding 4-(ethoxy)-3,5-dimethylphenylacetone to ethanol and adding ammonia solution. The experimental conditions are: 4-(ethoxy)-3,5-dimethylphenylacetone (1 mol), ethanol solvent, ammonia solution (salt removal agent), the reaction time is several hours, and the temperature is room temperature. Finally, by adding hydrochloric acid, the crystal form of Larocaine Hydrochloride is formed to obtain the final product.
Through the above steps, we successfully synthesized the local anesthetic drug Larocaine Hydrochloride. The chemical structure of the drug is simple, the synthesis method is relatively mature, and can be widely used in clinical practice. But at the same time, the drug has many side effects, so pharmacists should carefully understand the patient's history of allergies and other health conditions before using the drug, and strictly control the dosage to ensure the safety of the patient. If you need to buy lidocaine, please send an email to us for sales.