Tetracaine Hydrochloride is a highly effective local anesthetic that recessively blocks nerve function. It is clinically used in infiltration anesthesia, nerve block anesthesia, epidural anesthesia, etc. Compared with procaine, its local anesthetic effect is remarkable, and it has been widely used in clinical practice. It is found that the synthesis of p-but aminobenzoic acid is the key step in the synthesis of Tetracaine Hydrochloride, which has the disadvantages of unstable raw materials and low yield. In 1981, the scientists proposed the alkylation reaction of p-aminobenzoic acid and 1-bromobutane to synthesize p-but aminobenzoic acid.
However, due to the generation of dibutyl by-products cannot be avoided, and the unstable nature of the raw material itself, this route is not suitable for industrial production. Benzocaine was alkylated on amino group and transesterification reaction was performed to obtain the target product. Compared with the method using p-aminobenzoic acid as raw material, the advantage of this method is that the raw material is stable, but because the alkylation reaction produces a large proportion of dibutyl by-products, and the properties of the two are similar, the by-products are difficult to remove, making the reaction yield is low, the total yield is only 28%.
Tetracaine Hydrochloride Pharmacological effects
Tetracaine hydrochloride has strong local anesthetic effect and strong mucosal penetration, the anesthetic power is 10 ~ 15 times larger than procaine, and the toxicity is 10 ~ 20 times larger. It takes effect 1 ~ 3 minutes after administration and lasts 2 ~ 3 hours.
Tetracaine Hydrochloride is used for mucosal surface anesthesia, conduction anesthesia, epidural anesthesia and subarachnoid anesthesia. It is used for ophthalmic surface anesthesia without constricting blood vessels, damaging corneal epithelium and raising intraocular pressure.
Preparation of Tetracaine Hydrochloride
320.0kg of methyl is butylene was first added to the reaction kettle, followed by 40.0kg(207mol) of p-but aminobenzoic acid (ⅱ) and 56.8kg of anhydrous potassium carbonate. The oil bath was heated to 116℃ for reflux reaction for 4h, and the heating was stopped and slightly cooled for 0.5h. (β -chloroethyl) dimethylamine hydrochloride (ⅲ) 38.3kg (266mol) was added and heated to 116℃ for reflux reaction for 4h. After the reaction was completed and cooled to below 30℃, 127.0kg deionized water was added and stirred for 30min. After standing for 1h, the organic layer was separated and oil was obtained after drying and concentration. Then 169.0kg acetone was added to stir, and concentrated Tetracaine Hydrochloride acid was used to adjust the pH value to 3-4. A large number of crystals were precipitated. After freezing and crystallization for 12h, 53.0kg white solid was obtained, namely tetracaine hydrochloride, with the yield of 85.07% and HPLC purity of 99.34%.