~-ETHY YLPHENETHYLAMINE N
July 1966
469
1-Ethynylphenethylaminel - ~ L F R E DBURGER, STUART
E. ZI~\IMERJ1,4N,
Dcpnrtment of Chemistry, University os Virginia, Charlottesuik, Virginiz 23303 AND
E. J. ARIEKS
Departinent qf Pharmacology, T7niversity o j .Vzjmegen, .Vijmegen, The .\.etherlands Received F e b w a r y 81, 1966 l i t he&
)til
of l-eth?u)lpheiieth?-lamiiie is demihed. This ac,etj-leiiic.amine appears to protect pheiiethylbioloyicd dcaminatioii aiicl revealh tlie CNd activity of this compound.
-4number of acctyleiiic aniines have been found to possess SlhO-inhibitory,2 uriticho1inergic6 ganglionic bl~cking,~ arid antimicrobial properties.? Only a few of these compounds contained an ethynyl group CY to the aniino function where, by its bulk and unsaturated character, the ethynyl could decisively affect the reactions of the aniino group. The diniensions of the ethynyl group have been equated to those of the cyano group,6 3.2 (length) X 3.2 A (width), which compares with the corresponding diniensions of the methyl group, 3.3 X 2.0 A,' Thus ethynyl is shorter and more compact than ethyl arid therefore amines containing the ethynyl group should offer less steric hindrance to fit a t enzyme surfaces than the corresponding ethyl derivatives which as a rule are considerably less biologically active than their methyl honiologs.8 We are reporting the synthesis arid pharmacological study of the ethynyl analog of aniphetamine, 1-ethynylpheriethylaniirie (2-aniino-l-phenyl-lbutync, I). The compound was synthesized by condensing phenylacetaldehyde with ethyriylniagriesiuiii bromide arid treating the tosylate (111) of the resulting l-ethynylphenethyl alcohol (11) with sodaniide. Both the secondary alcohol and acetylenic amine exhibited in HCECAIgBr
CcHjCHpCHO
TsCl
--+
C~H~CH~CHOHCESH +
I1
C=CH
I11
C=CH
I
(1) Suygorted, in part, by Grants NI%-1445and GJI-001882 from the National Institutes of Health, U. S. PuLlic IIealth Service, t o whom we express our appreciation. (2) For references see C. L. Zirkle and C. Kaiser in "Psychopharmacological .'igents," Vol. I, 51.Gordon, Ed., Academic Press Inc., S e w York, N. Y . , 1964, p 445. ( 3 ) (a) R . Dahlbom and R . Mollberg, Acta Chem. Scand., 17, 916 (1963); (b) R. Dahlbom and B. Hanson, i b i d . , 17, 2354 (1963). (41 (a) C. h i n s a o r t h and N. R. Easton, J . O r g . Chem., 26, 3776 (1961); (1)) N. R . Easton, R . D. Dillard, JV. J. Doran, A1. Lirezey, and D. E . Llorrison, ibid., 26, 3772 (1961); ( c ) K. R . Easton, Aibstracts, 138th National Meeting of the .4merican Chemical Society, New York, N. Y . . Sept 1960, p 4 6 - 0 ; (d) C. n'.Ryan, N. R. Easton, R. D. Dillard, and F. G. Henderson, J . .\fed. P h u r m . Chem., 5, 780 (1962); (e) J. L. Neumeyer. J. G. Cannon, and .J. P.Euckley, ibid., 5, 784 (1962): (f) J . H. Riel and F. DiPierro, J . A m . C h e m . Soc., 80, 4609 (1958). ( 5 ) (a) H. Gershon, J. Shapira, J. 9. RIeek, and I
