TETRAZEPAM

Chemical properties

Light yellow or yellow crystalline powder.

Originator

Myolastan,Clin-Comar-Byla,France,1969

The Uses of TETRAZEPAM

Tetrazepam is a muscle relaxant (skeletal). This is a controlled substance (depressant).

Definition

ChEBI: Tetrazepam is a benzodiazepine.

Manufacturing Process

1,7-Dichloro-5-Cyclohexyl-2-Oxo-2,3-Dihydro-1H-Benzo[f]Diazepine-1,4: (a) Process Using Sodium Hypochlorite - 40 ml of a solution of sodium hypochlorite of 14.5 British chlorometric degrees are added to a suspension of 5.4 grams of 7-chloro-5-cyclohexyl-2-oxo-2,3-dihydro-1H-benzo[f]diazepine- 1,4 in 80 ml of methylene chloride. The mixture is stirred at room temperature for 15 minutes; the solid dissolves rapidly. The organic layer is decanted, washed with water, dried over anhydrous sodium sulfate and the solvent evaporated under reduced pressure without exceeding a temperature of 30°C. The residue is taken up in a little diisopropyl ether and the crystals which form are dried. They are recrystallized as rapidly as possible from ethyl acetate. Colorless crystals are obtained (3.9 grams; yield, 85%); MP = 163°C, with decomposition.
(b) Process Using Tertiary-Butyl Hypochlorite - 1.2 grams of tertiary-butyl hypochlorite are added to a suspension of 2.7 grams of 7-chloro-5-cyclohexyl- 2-oxo-2,3-dihydro-1H-benzo[f]diazepine-1,4 in 20 ml of methylene chloride and the mixture is stirred and at the same time cooled in a water bath for 30 minutes. The solid dissolves in about 15 minutes. The product is evaporated to dryness under reduced pressure at a temperature below 40°C. The residue is taken up in diisopropyl ether and the crystals which separate are dried. Colorless crystals are obtained (2.8 grams; yield, 98%); MP = 161° to 162°C, with decomposition, according to US Patent 3,551,412.
7-Chloro-5-(1'-Chlorocyclohexyl)-2-Oxo-2,3-Dihydro-1H-Benzo[f]Diazepine- 1,4: A solution of 117 grams of the compound prepared above in 450 ml ethyl acetate is heated under reflux until a precipitate begins to form. From then onwards reflux is continued until a negative reaction is obtained when the reaction mixture is tested with a solution of sodium iodide in acetone. The reaction mixture is left to cool and the solid which separates is dried. Colorless crystals are obtained (76 grams), MP = 194° to 195°C, with decomposition. A second portion (14 grams) is isolated by concentrating the mother liquor, MPk = 194° to 195°C, with decomposition. The total yield is 77%. The melting point is raised to 196° to 197°C by recrystallization from ethyl acetate.
7-Chloro-5-(1'-Cyclohexenyl)-2-Oxo-2,3-Dihydro-1H-Benzo[f]Diazepine-1,4: 68 grams of 7-chloro-5-(1'-chlorocyclohexyl)-2-oxo-2,3-dihydro-1Hbenzo[ f]diazepine-1,4, 34 grams of lithium carbonate and 17 grams of lithium bromide and 340 ml of anhydrous dimethylformamide are placed in a threenecked flask equipped with a mechanical stirrer, immersion thermometer and a reflux condenser connected with a bubble counter.
The reaction mixture is gradually heated, with stirring, until evolution of carbon dioxide commences (about 100°C) and the temperature is maintained thereat until the reaction ceases. The temperature is then raised to 110°C and held thereat for 15 minutes.
The reaction mixture is allowed to cool and the mineral salts separated and dried. The solvent is evaporated under reduced pressure and the residue dissolved in water. It is allowed to crystallize, dehydrated, dried and then recrystallized from ethyl acetate. The product is yellowish crystals (47.5 grams; yield, 80%); MP = 207° to 208°C.
7-Chloro-5-(1'-Cyclohexenyl)-1-Methyl-2-Oxo-2,3-Dihydro-1HBenzo[ f]Diazepine-1,4: 9.7 grams of sodium methylate are added to a solution of 16.5 grams of 7-chloro-5-(1'-cyclohexenyl)-2-oxo-2,3-dihydro-1Hbenzo[ f]diazepine-1,4 dissolved in 120 ml of dry dimethylformamide and the mixture stirred for one-half hour. The reaction mixture is cooled in a water bath and a solution of 33.8 grams of methyl iodide dissolved in 35 ml of anhydrous dimethylformamide is then slowly added with stirring. The solution becomes dark brown in color and a precipitate forms. It is stirred for 2 hours, then diluted with a large volume of water and extracted with ethyl acetate. The ethyl acetate solution is washed with water, dried over anhydrous sodium sulfate and the solvent evaporated under reduced pressure. The residue is crystallized from a small volume of ethyl acetate. Brownish yellow crystals are obtained (9 grams; yield, 52%), MP = 144°C.

Therapeutic Function

Muscle relaxant

Contact allergens

Tetrazepam is a benzodiazepine compound used systemically as a myorelaxant. It may induce skin rashes such as maculo-papular eruption, Stevens-Johnson syndrome, or photosensitivity. Occupational sensitization can be observed in pharmaceutical plants. Sensitization generally does not concern other benzodiazepines.