2-METHYL-2-(1-METHYLPROPYL)-1,3-PROPANEDIOL DICARBAMATE

Description

Mebutamate is a biscarbamate drug that has anxiolytic, sedative, and antihypertensive effects. It is marketed under many trade names, including Capla and Dormate. Its preparation was reported in a 1959 US patent to Carter Products.
It is less well known that mebutamate is also a hypnotic. In a?1967 study, L. Tetreault, P. Richer, and J. M. Bordeleau in Montreal found that, at a dose of 600 mg, mebutamate has hypnotic properties that “affect the duration and quality of sleep induction, and the duration and quality of sleep, without disturbing the state of the subject upon awakening and during the morning.” A higher dose (900 mg) did not change the overall effect, which was “consistently between that of secobarbital at 200 mg and 100 mg.” The authors did not observe any significant side effects.

Originator

Capla,Wallace,US,1961

The Uses of 2-METHYL-2-(1-METHYLPROPYL)-1,3-PROPANEDIOL DICARBAMATE

Antihypertensive.

Background

Mebutamate is a sedative and anxiolytic drug with anti-hypertensive (blood pressure lowering) effects comparable to those of other barbiturates but is only around 1/3rd the potency of secobarbital as a sedative. Side effects include dizziness and headaches.

Definition

ChEBI: Mebutamate is an organic molecular entity.

Manufacturing Process

The following example illustrates the preparation of 2-methyl-2-sec-butyl-1,3- propanediol:
92 g of diethyl-sec-butyl methyl malonate were reduced in the usual manner using 22.8 g of lithium aluminum hydride in a suitable volume of anhydrous ethyl ether. The mixture was treated with 10% sulfuric acid and the ether soluble components extracted. The ether solution was dried, using a suitable drying agent, and the residue obtained by the removal of the ether was purified by distilling under reduced pressure. This material was further purified by redistillation. Approximately 46 g of 2-methyl-2-sec-butyl-1,3-propanediol were obtained as a clear colorless liquid, boiling point 92°C to 97°C (0.1 mm pressure).
The following example describes the preparation of 2-methyl-2-sec-butyl-1,3- propanediol dicarbamate using the urethane exchange method:
14.6 g of 2-methyl-2-sec-butyl-1,3-propanediol and 18.7 g ethyl urethane are dissolved in about 100 ml anhydrous toluene. 3 g of aluminum isopropylate are added and the mixture distilled to remove the ethyl alcohol formed in the condensation of ethyl urethane and the diol. The alcohol distills in the form of an azeotrope with toluene. Distillation is continued until the theoretical quantity of ethanol has been removed. The toluene is distilled from the mixture under reduced pressure and the residue dissolved in hot aqueous isopropanol solution. The hot solution is filtered and allowed to cool, whereupon approximately 14 g of product separates. The purified product represents a yield of about 60% of theoretical and melts at 77°C to 79°C.

brand name

Dormate (Medpointe).

Therapeutic Function

Antihypertensive

Metabolism

Not Available