Laboratory Synthesis Of Benzatropine

Chemical Synthesis Of Benzatropine

Benzatropine Use: parasympatholytic, antiparkinsonian

Benzatropine MW: 307.44

MF: C21H25NO
LD50: 25 mg/kg (M, i.v.)
CN: endo- 3- (di phenyl methoxy)- 8- methyl- 8- aza bi cyclo [3 .2 .1 ]octane 

Benzatropine mesylate
RN: 132-17-2 EINECS: 205-048-8
MW: 403.54 

MF: C21H25NO · CH4O3S
LD50: 24 mg/kg (M, i.v.); 91 mg/kg (M, p.o.);940 mg/kg (R, p.o.)

Reference(s):
US 2 595 405 (Merck & Co.; 1952; prior. 1949).

Benzatropine solubility :Soluble in chloroform.

Benzatropine Mesilate

Synonyms. Benzatropine Methanesulfonate; Tropine Diphenylmethyl Ether.

Proprietary names. Bensylate; Cogentin.

C₂₁H₂₅NO,CH₄O₃S=403.5

CAS—132–17–2

A white, slightly hygroscopic, crystalline powder. M.p. 141° to 145°.
Soluble 1 in 0.7 of water, 1 in 1.5 of ethanol, and 1 in 2 of chloroform; practically insoluble in ether.

Dissociation Constant.

Benzatropine pK_a10.0 (20°).

Partition Coefficient.

Benzatropine Log P(heptane), 0.4.

Colour Tests.

Mandelin's Test—yellow; Marquis Test—yellow.

Benzatropine Thin–layer Chromatography.

System TA—Rf 13; system TB—Rf 26; system TC—Rf 06; system TL—Rf 02; system TAE—Rf 06. (Acidified iodoplatinate solution, positive.)

Benzatropine Gas Chromatography.

System GA—RI 2302; system GB—RI 2423.

Benzatropine High Performance Liquid Chromatography.

System HA—k 3.7 (tailing peak).

Benzatropine Ultraviolet Spectrum.

Aqueous acid—253, 259 nm (A¹₁=14.5a).

Benzatropine Infra–red Spectrum.

Principal peaks at wavenumbers 1054, 700, 742, 1191, 1204, 1075 cm⁻¹ (KBr disk).

Benzatropine Mass Spectrum.

Principal ions at m/z 83, 140, 82, 124, 96, 97, 42, 125.

Benzatropine Quantification

High performance liquid chromatography.

In plasma—K. Selinger et al.,J. Chromatogr.,1989, 49111, 248–252.

Disposition in the Body.

Absorbed after oral administration.

Benzatropine Toxicity

In a fatality attributed to the ingestion of an unknown quantity of benzatropine tablets, the following postmortem concentrations were reported: blood 0.7 mg/L, liver 1.6 μg/g, urine 0.8 mg/L. In a second case a liver concentration of 2.3 μg/g was found. [G. del Villar and M. Liddy,Bull. Int. Assoc. Forensic Toxicol.,1976, 122, 11–12.]
A 41–year–old male with a history of schizophrenia and drug abuse was found dead. Benzatropine was found at a concentration of 0.183 mg/L in his blood and 7.12 mg/L in his urine. [T. G. Rosano et al.,J. Anal. Toxicol.,1994, 186, 348–353.]

Benzatropine Dose.

0.5 to 6 mg of benzatropine mesilate daily.

Reference

Clarke's Analysis of Drugs and Poisons