2-Dimethylamino-l-chloropropane

CK1H14N4 43171-03-5) see Azapropazone 2-dimethylamino-l-methyIethyl chloride see under l-dimethylamino-2-chloropropane... 

Acetyl phenothiazine l-Dimethylamino-2-chloropropane Sodium hydride... 

A solution of thionyl chloride (37 ml, 0.48 mol) in chloroform (20 ml) was added slowly, with stirring, to a cooled (ice/water) solution of S-(+)-l-dimethylamino-2-propanol (30.6 g, 0.32 mol) in chloroform (85 ml). When the addition was complete a precipitate formed. The mixture was allowed to warm to room temperature over 30 min and then heated to reflux for a further 30 min. The precipitate redissolved on heating but then the product crystallized out from the boiling solvent as it formed. More chloroform (20 ml) was needed to maintain the stirring. The cooled mixture was diluted with ether and filtered. The 45.0 g (96%) of crude product was isolated. This was recrystallised from 2-propanol as in the other series to give 30.9 g (65%) of R-(-)-l-dimethylamino-2-chloropropane, melting point 192°-193°C. 

A 50% w/v solution of sodium hydroxide in water (12.5 ml, 0.32 mol) was added to a mechanically stirred suspension of diphenylacetonitrile (15.0 g,0.08 mol) and dibenzo-18-crown-6 (0.5 g, cat.) in dimethylsulphoxide (12.5 ml). The color rapidly deepened to an orange/brown. R-(-)-l-Dimethylamino-2-chloropropane (30.0 g, 0.095 mol) was added in portions over 30 min, this caused the temperature to rise to 30°C. After the addition was complete the mixture was warmed to 45°-50°C (water bath) and stirred for a further hour. The reaction mixture was then allowed to cool to room temperature and was poured into ice/water (250 ml) and extracted with ethyl acetate (3 times 150 ml). The combined extracts were dried (MgS04) and filtered and evaporated down to -100 ml. The product was extracted into IN HCI (100 ml+50 ml) and this was back washed with ethyl acetate. The aqueous was basified with 2 M sodium hydroxide and extracted into ethyl acetate (3 times 100 ml). The extracts were washed with brine (70 ml), dried (MgS04), and evaporated down to a yellow oil. This was chilled and triturated with cold hexane (50 ml) to give a white solid which was collected by filtration and washed thoroughly with a further portion of cold hexane (100 ml). 14.65 g (33%) of S-(+)-2,2-diphenyl-4-dimethylaminopentanenitrile were obtained, melting point 100°-101°C (recrystallised from hexane). 

Phenothiazine (20 g) is heated under reflux for 1 hour with sodium amide (5 g) in xylene (80 ml). A solution of l,3-bis(dimethylamino)-2-chloropropane (27 g) (prepared by a method analogous to that described in Ingold and Rothstein J.C.S. 1931, 1676) in xylene (30 ml) is then added over 2 hours. Heating is continued for a further 1 hour and then the mixture is taken up in water (270 ml) and hydrochloric acid (d=1.19 20 ml). The decanted acid layer is treated with caustic soda (d 1.33 25 ml) and the base is extracted with ether (2 x 50 ml) which is then dried over potassium carbonate. On distillation there is obtained at 218-220°C/0.6 mm Hg a mixture (20 g) containing a major proportion of 10-[2,3-bis(dimethylamino)-l-propyljphenothiazine and a minor proportion of 10-[l,3-bis(dimethylamino)-l-propyljphenothiazine. 

A solution of 3-cyanophenthiazine (10 g) in anhydrous xylene (75 cc) is heated under reflux and treated with 95% sodium amide (2.15 g). The heating is continued for 1 hour and then a solution of l-dimethylamino-2-methyl-3-chloropropane (7.05 g) in xylene (70 cc) is added over 15 minutes. The mixture is heated under reflux for 20 hours and then cooled. The reaction mixture is treated with water (40 cc) and N methane-sulfonic acid (75 cc). 

Ethyl-10H-phenothiazine l-Dimethylamino-2-methyl-3-chloropropane Methanesulfonic acid... 

Replacement of one of the phenyl groups by an alkyl group of similar bulk, on the other hand, alters the biologic activity in this series. Alkylation of phenylacetonitrile with isopropyl bromide affords the substituted nitrile, 136. Treatment of the anion prepared from 136 with strong base with 2-dimethylamino-l-chloropropane gives isoaminile (137). It is of note that alkylation of this halide, isomeric with that used in the early methadone synthesis, is apparently unaccompanied by isomer formation. Isoaminile is an agent with antitussive activity. 

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