ethoheptazine Property

Melting point:

25°C

Boiling point:

bp1 133-134°; bp0.5 127-129°; bp0.3 128-130°

Density 

d426 1.038

refractive index 

nD26 1.5210; nD28 1.5220

pka

pKa 8.45 (Uncertain)

Safety

Hazardous Substances Data

77-15-6(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

ethoheptazine Chemical Properties,Usage,Production

Chemical Properties

Liquid.

Originator

Zactane,Wyeth,US,1957

Uses

Medicine (analgesic).

Definition

ChEBI: Ethoheptazine is a member of azepanes.

Manufacturing Process

As a starting material, phenylacetonitrile was reacted with N-(2- chloroethyl)dimethylamine. This then underwent the following reaction sequence.
Preparation of 1-Dimethylamino-3-Cyano-3-Phenyl-6-Bromohexane: 65.8 grams (0.35 mol) of 2-phenyl-4-dimethylaminobutyronitrile in 350 cc of absolute ether was dripped into a stirred suspension of 17.5 grams (0.45 mol) of sodamide in 350 cc of absolute ether during 1 hour, keeping the reaction mixture under a dry nitrogen atmosphere. The mixture was stirred an additional hour at room temperature and then 1 hour at reflux temperature. The mixture was diluted with 250 cc of absolute ether, cooled in an ice bath, then, while stirring, a solution of 74.7 grams (0.37 mol) of trimethylene bromide in 250 cc of absolute ether added at once. The yellow suspension continued to be stirred at ice-bath temperature for 1 hour, then at room temperature for 1 hour, and finally at reflux temperature for 3 hours. The mixture was cooled and the sodium bromide, which had precipitated in quantitative yield, was filtered off and washed with ether. The light yellow ethereal filtrate contained the product. This compound could be stored for some time in a hydrocarbon solvent, e.g., n-heptane, at +5°C.
Preparation of 4-Phenyl-4-Cyano-N-Methyl Azacycloheptane Methobromide: A 0.1 M nitrobenzene solution of 1-dimethylamino-3-cyano-3-phenyl-6- bromohexane was kept at 100°C for 1 hour whereby the quaternary salt precipitated out; MP 246° to 247°C.
Preparation of 4-Phenyl-4-Cyano-N-Methyl Azacycloheptane: 6.2 grams (0.02 mol) of the methobromide quaternary salt was suspended in 150 cc of tetralin. While vigorously stirring, the mixture was heated to its reflux temperature, whereupon the solid began to disintegrate and go into solution. The stirring and refluxing was continued 1 hour, then the mixture cooled, water added, and the layers separated. The tetralin solution was extracted with 3 M aqueous hydrochloric acid, the acid extract washed with ether, then made alkaline with aqueous sodium hydroxide and extracted with ether. The ether extracts were dried, filtered, and the solvent distilled off. Vacuum distillation of the liquid residue gave the tertiary amine, BP 119° to 121°C/0.25 mm.
Preparation of 4-Phenyl-4-Carbethoxy-N-Methyl Azacycloheptane: A solution of 8.4 grams (0.04 mol) of the cyclic aminonitrile in 10.6 grams concentrated sulfuric acid and 2.6 grams water was kept at 110° to 120°C (bathtemperature) for 3 hours. Then, while repeatedly adding absolute ethanol, 95% aqueous ethanol was slowly distilled off during 16 hours. The reaction mixture was concentrated to 50 cc, cooled, poured into 200 cc of a cold saturated aqueous solution of sodium carbonate and extracted with ether. The ether extract after drying and filtering yielded, by distillation, the aminoester, BP 122° to 124°C/0.3 mm.

Therapeutic Function

Analgesic