DIMETHINDENE Property

Melting point:

50 - 53°C

Boiling point:

424.35°C (rough estimate)

Density 

1.0073 (rough estimate)

refractive index 

1.5640 (estimate)

storage temp. 

Refrigerator, under inert atmosphere

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

9.58±0.28(Predicted)

color 

Pale Brown to Light Brown

Water Solubility 

238.6mg/L(37 ºC)

Hazard and Precautionary Statements (GHS)

DIMETHINDENE Chemical Properties,Usage,Production

Originator

Fenistil,Zyma,W. Germany,1961

Definition

ChEBI: Dimetindene is an indene.

Manufacturing Process

26 grams of 2-ethylpyridine is added dropwise with cooling to 20°C and in an atmosphere of nitrogen to a stirred solution of 650 ml of an 0.37 molar solution of phenyl lithium in benzene. After two hours a solution of 10 grams of 2-(2-dimethylaminoethyl)-indan-1-one in 50 ml of dry ether is added over a period of five minutes while stirring and cooling to room temperature. After standing for 24 hours the organo-lithium compounds are decomposed by the addition of 50 ml of water with external cooling. After separating the water phase from the organic solution, the latter is washed several times with 50 ml of water, and then extracted with a mixture of 40 ml of concentrated hydrochloric acid and 100 ml of water.
The acidic solution, containing the 2-(2-dimethylaminoethyl)-1-[1-(2-pyridyl)- ethyl]-indan-1-ol is heated on the steam bath for thirty minutes to effect dehydration to the desired indene derivative. The solution is cooled, made strongly basic with an aqueous solution of ammonia and then extracted with ether. The ether phase is dried over sodium sulfate, filtered, evaporated and the residue distilled.
At 15 mm pressure the excess of 2-ethylpyridine is removed, at 120°C/0.5 mm some unreacted 2-(2-dimethylaminoethyl)-indene distills and at 165°- 175°C/0.5 mm the 2-(2-dimethylaminoethyl)-3-[1-(2-pyridyl)-ethyl]-indene is collected. It may be converted to an aqueous solution of the dihydrochloride by dissolving it in the appropriate amount of dilute hydrochloric acid.
To a solution of 1.0 gram of 2-(2-dimethylaminoethyl)-3[1-(2-pyridyl)-ethyl]- indene in 10 ml of ethanol is added while stirring and heating 0.4 gram of maleic acid. On cooling the 2-(2-dimethylaminoethyl)-3-[1-(2-pyridyl)-ethyl]- indene maleate crystallizes, is filtered off, washed with a small amount of ethanol and recrystallized from ethanol, MP 158°C.

Therapeutic Function

Antihistaminic

Synthesis

Benzylmalonic acid is esterified with dihydropyran and reacted with sodium hydride and 2-dimethylaminoethyl chloride in toluene to give ditetrahydropyranyl-2-benzyl-2- (2-dimethylaminoethyl)malonate, which is cyclized with the help of polyphosphoric acid to 2-(2-dimethylaminoethyl)-indan-1-one. This compound reacts with 2-ethylpyridine and phenyllithium to give the carbinol, which is dehydrated by heating to dimetindene .