KETAMINE HYDROCHLORIDE SELECTIVE NMDA AN TAGO Property

Melting point:

92-93°

Boiling point:

363.8±42.0 °C(Predicted)

Density 

1.0982 (rough estimate)

refractive index 

1.6330 (estimate)

pka

7.5(at 25℃)

EPA Substance Registry System

Cyclohexanone, 2-(2-chlorophenyl)-2-(methylamino)- (6740-88-1)

Safety

RIDADR 

3249

HazardClass 

6.1(b)

PackingGroup 

III

Hazardous Substances Data

6740-88-1(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

KETAMINE HYDROCHLORIDE SELECTIVE NMDA AN TAGO Chemical Properties,Usage,Production

Originator

Ketanest,Parke Davis,W. Germany,1969

Uses

Anesthetic.

Definition

ChEBI: Ketamine is a member of the class of cyclohexanones in which one of the hydrogens at position 2 is substituted by a 2-chlorophenyl group, while the other is substituted by a methylamino group. It has a role as an intravenous anaesthetic, a NMDA receptor antagonist, an analgesic, a neurotoxin, an environmental contaminant and a xenobiotic. It is a member of cyclohexanones, a secondary amino compound and a member of monochlorobenzenes.

Manufacturing Process

The 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine used as an intermediate is prepared as follows. To the Grignard reagent prepared from 119.0 g of cyclopentyl bromide and 19.4 g of magnesium is added 55.2 g of o-chlorobenzonitrile. The reaction mixture is stirred for 3 days and thereafter hydrolyzed in the usual manner. From the hydrolysis there is obtained ochlorophenylcyclopentylketone, BP 96° to 97°C (0.3 mm), nD251.5452. To 21.0 g of the ketone is added 10.0 g of bromine in 80 ml of carbon tetrachloride.
1-Bromocyclopentyl-(o-chlorophenyl)-ketone, BP 111° to 114°C (0.1 mm) is isolated in the usual manner. Since it is unstable, it must be used immediately. The bromoketone (29.0 g) is dissolved in 50 ml of liquid methylamine. After one hour, the excess liquid methylamine is allowed to evaporate. The organic residue is dissolved in pentane, and upon evaporation of the solvent, 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine, MP 62°C, is isolated.
1-Hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine (2.0 g) is dissolved in 15 ml of Decalin and refluxed for 2,5 hours. After evaporation of the Decalin under reduced pressure, the residue is extracted with dilute hydrochloric acid, the solution treated with decolorizing charcoal, and the resulting acidic solution is made basic. The liberated product, 2-methylamino- 2-(o-chlorophenyl)-cyclohexanone, after crystallization from pentane-ether, has MP 92° to 93°C. The hydrochloride of this compound has MP 262° to 263°C.

brand name

Ketalar (Parkdale).

Therapeutic Function

Anesthetic

Mechanism of action

The mode of action of ketamine differs from that of the barbiturates. It suppresses the activities of the cerebral cortex (consciousness) and the thalamic pain pathways (analgesia). Parts of the upper brainstem and the limbic system are not affected (so-called dissociative analgesia). The patient exhibits a characteristic superficial sleep with complete elimination of pain. Because of the psychomotor side effects, combination with neuroleptics and tranquilizers is necessary. Ketamine is used especially in pediatrics. The usual preparations are 0.1 % and 0.5 % solutions.

Clinical Use

Ketamine is a short-acting anesthetic effective for 5 – 30 min, depending on the amount injected. It is suitable for diagnostic purposes and for surgical procedures that do not require muscle relaxation. The occasional hallucinations that occur during anesthesia suggest a chemical relationship to phencyclidine, which was used as a short-acting anesthetic until identified as a dangerous drug of abuse.

Synthesis

It is prepared by bromination of o-chlorophenyl cyclopentyl ketone, which is then reacted with methylamine to give the methylimino alcohol. Thermolysis of the imino hydrochloride yields ketamine by ring expansion :