SHORT THE CONDENS-4TION OF PHENYLETHPLAMINE ETC. 269 XLIV.-7'1w Condensation of PhenylethylaminP zviih' s-Dichlorodimethyl Ether. By WALLACE FRANK SHORT. BY the action of p-phenylethylarnine on an excess of methylal in presence of concentrated hydrochloric acid a t loo" Pictet and Spengler (Ber. 191 1 44 2030) obtained tetrahydroisoquinoline in 3 6 % yield. By a similar method Pictet and Gams (Ber. 1911, 44 2629) prepared hydronorhydrastinine from homopiperonyl-amine but Decker and Beclier (Ber. 1912 45 3404) who repeated the experiments obtained a base of the type NHR*CH,*NHR. Phenylethylamine itself yielded p -phenylethyldirnethylamine when condensed with an excess of formalin a t 130-140". The sam 270 SHORT THE CONDENSATION OF PHENYLETHYLAMINE ETC. authors have shown (Annalen 1913 395 342) that homopiperonyl-amine and other derivatives of p-phenylethylamine react readily at room temperature with an equimolecular quantity of an aldehyde to form the alkylidene derivative which is converted into a tetra-hydroisoquinoline derivative by a suitable catalyst,.Rosenmund (Ber. Deut. pharm. Ges. 1919 29 200) condensed homopiperonylamine (2 mols.) with s-dichlorodimethyl ether (1 mol.) in ethereal solution and obtained homopiperonylaminomethanol as a very unstable oil which was converted almost quantitatively into hydronorhydrastinine by heating a t 100" with 10% hydrochloric acid. In view of the above results it appeared to be of interest to determine whether a good yield of tetrahydroisoquinoline could be obtained by the condensation of p-phenylethylamine with the so-called '' chloromethyl alcohol." The products of the reaction were tetrahydroisoquinoline (yield 59 %) di( p-~henyZethyZamino)-methane and bases of unknown constitution.E X P E R I M E N T A L. p-Phenylethylamine was obtained in 30% yield (Wohl and Berthold Ber. 1910 43 2183). s-Dichlorodimethyl ether was prepared by Stephen Short and Gladding's method (J. 1920, 117 513). A mixture of 31.5 g. (2 mols.) of p-phenylethylamine hydro-chloride 14.4 g. of s-dichlorodimethyl ether (12 mols. equivalent to 2& mols. of chloromethyl alcohol) 0.5 g. of anhydrous zinc chloride and 100 C.C. of dry ether was cooled to room temperature, stirred for 8 hour and heated for 4 hours on the water-bath. Dis-tillation in a vacuum left a brown syrup which was dissolved in water the solution made alkaline and extracted with ether.The oily residue from the ethereal extract on solution in dilute hydro-chloric acid and treatment with sodium nitrite gave a yellow oil, which on reduction with tin and concentrated hydrochloric acid, deposited p-phenylethyl chloride. The aqueous layer was extracted with ether made alkaline with caustic soda and again extracted with ether. The second extract was distilled up to 235" and the distillate converted into a picrate which crystallised thrice from alcohol melted a t 196" ; the base generated therefrom by additlion of ammonia had b. p. 234"/763 mm. (yield 15.7 g . ) (Found C = 81.10; H = 8-39. Calc. for C,H,,N C = 81-15; H = 8.33%). These constants are in good agreement with those given in the literature for tetrahydroisoquinoline and show that the product cannot be Becker and Decker's p-phenylethyldimethylamine.The residue in the distilling flask was dissolved in hydrochloric acid boiled with animal charcoal and recrystallised several time BURGESS AND LOWRY NEW HALOGEN DERIVATIVES ETC. 271 froni water. The colourless crystals so obtained did not melt at 300". The base liberated with caustic soda consisted of white needles of di( p-phenyZethyEamino)methane m. p. 153" and absorbed carbon dioxide from the air (Found C = 80.16; H = 8.73; N = 10.S2. C,,€I,,N requires C = 80.25; H = 8.72; N = 1142%). About 107; of the p-phenylethylamine is converted into this secondary diaminc. The diacetyl derivative forms silky needles m.p. 191". My thanks are due to Mr. F. H. V. Fielder B.Sc. for assistance UNIVERSITY COLLEGE, in preparing the p-phenylethylamine for this investigation. AUCXLAND NEW ZEALAND. [Received October 3let 1924. SHORT THE CONDENS-4TION OF PHENYLETHPLAMINE ETC. 269 XLIV.-7'1w Condensation of PhenylethylaminP zviih' s-Dichlorodimethyl Ether. By WALLACE FRANK SHORT. BY the action of p-phenylethylarnine on an excess of methylal in presence of concentrated hydrochloric acid a t loo" Pictet and Spengler (Ber. 191 1 44 2030) obtained tetrahydroisoquinoline in 3 6 % yield. By a similar method Pictet and Gams (Ber. 1911, 44 2629) prepared hydronorhydrastinine from homopiperonyl-amine but Decker and Beclier (Ber. 1912 45 3404) who repeated the experiments obtained a base of the type NHR*CH,*NHR.Phenylethylamine itself yielded p -phenylethyldirnethylamine when condensed with an excess of formalin a t 130-140". The sam 270 SHORT THE CONDENSATION OF PHENYLETHYLAMINE ETC. authors have shown (Annalen 1913 395 342) that homopiperonyl-amine and other derivatives of p-phenylethylamine react readily at room temperature with an equimolecular quantity of an aldehyde to form the alkylidene derivative which is converted into a tetra-hydroisoquinoline derivative by a suitable catalyst,. Rosenmund (Ber. Deut. pharm. Ges. 1919 29 200) condensed homopiperonylamine (2 mols.) with s-dichlorodimethyl ether (1 mol.) in ethereal solution and obtained homopiperonylaminomethanol as a very unstable oil which was converted almost quantitatively into hydronorhydrastinine by heating a t 100" with 10% hydrochloric acid.In view of the above results it appeared to be of interest to determine whether a good yield of tetrahydroisoquinoline could be obtained by the condensation of p-phenylethylamine with the so-called '' chloromethyl alcohol." The products of the reaction were tetrahydroisoquinoline (yield 59 %) di( p-~henyZethyZamino)-methane and bases of unknown constitution. E X P E R I M E N T A L. p-Phenylethylamine was obtained in 30% yield (Wohl and Berthold Ber. 1910 43 2183). s-Dichlorodimethyl ether was prepared by Stephen Short and Gladding's method (J. 1920, 117 513). A mixture of 31.5 g. (2 mols.) of p-phenylethylamine hydro-chloride 14.4 g. of s-dichlorodimethyl ether (12 mols.equivalent to 2& mols. of chloromethyl alcohol) 0.5 g. of anhydrous zinc chloride and 100 C.C. of dry ether was cooled to room temperature, stirred for 8 hour and heated for 4 hours on the water-bath. Dis-tillation in a vacuum left a brown syrup which was dissolved in water the solution made alkaline and extracted with ether. The oily residue from the ethereal extract on solution in dilute hydro-chloric acid and treatment with sodium nitrite gave a yellow oil, which on reduction with tin and concentrated hydrochloric acid, deposited p-phenylethyl chloride. The aqueous layer was extracted with ether made alkaline with caustic soda and again extracted with ether. The second extract was distilled up to 235" and the distillate converted into a picrate which crystallised thrice from alcohol melted a t 196" ; the base generated therefrom by additlion of ammonia had b.p. 234"/763 mm. (yield 15.7 g . ) (Found C = 81.10; H = 8-39. Calc. for C,H,,N C = 81-15; H = 8.33%). These constants are in good agreement with those given in the literature for tetrahydroisoquinoline and show that the product cannot be Becker and Decker's p-phenylethyldimethylamine. The residue in the distilling flask was dissolved in hydrochloric acid boiled with animal charcoal and recrystallised several time BURGESS AND LOWRY NEW HALOGEN DERIVATIVES ETC. 271 froni water. The colourless crystals so obtained did not melt at 300". The base liberated with caustic soda consisted of white needles of di( p-phenyZethyEamino)methane m. p. 153" and absorbed carbon dioxide from the air (Found C = 80.16; H = 8.73; N = 10.S2. C,,€I,,N requires C = 80.25; H = 8.72; N = 1142%). About 107; of the p-phenylethylamine is converted into this secondary diaminc. The diacetyl derivative forms silky needles m. p. 191". My thanks are due to Mr. F. H. V. Fielder B.Sc. for assistance UNIVERSITY COLLEGE, in preparing the p-phenylethylamine for this investigation. AUCXLAND NEW ZEALAND. [Received October 3let 1924.