June, 1947
COMMUNICATIONS TO THE EDITOR
HALOGENATED THIOPHENE DERIVATIVES AS ANTIHISTAMINE AGENTS
Sir :
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( 2 - pyridyl) - N' - (5 - chloro - 2 - thenyl) - ethylenediamine (I, X = Cl), b. p. 155-156' at 1 mm., was obtained similarly in 62% yield. The monohydrochloride of this compound melted at 106108'. Anal. Calcd. for C14H19C12N3S:C, 50.6; H, 5.8; N, 12.6. Found: C, 50.8, 50.9; H, 6.0, 6.2; N, 12.3, 12.3. These compounds will be described more fully in a further publication along with other compounds prepared in the course of this study.
The preparation of N,N-dimethyl-N'-(a-pyridyl)-N'-(2-thenyl)-ethylenediamine (I, X = H) and its antihistamine activity have been reported recently.' Thiis compound is t h e thiophene analog of N,N-dimethyl-N '-( 2-pyridyl) -N '-benzylethylenediamine (Pyribenzamine) . Prior to the publication of these results, we had also prepared this compound and pharmacological CHEMOTHERAPY DIVISION R. C. CLAPP tests had been carried out in these L a b ~ r a t o r i e s . ~STAMFORD RESEARCH LABORATORIES J. H. CLARK The results obtained confirm those reported AMERICANCYANAMID COMPANY J. R. VAUGHAN J. P. ENGLISH CONNECTICUT earlier,' in that the compound is of the same order STAMFORD, G. W. ASDERSON of activity as is Pyribenzamine in vivo and of the RECEIVED MAY17, 1947 same order of acute toxicity. #
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STREPTOMYCIN. V.' DEGRADATION OF STREPTOMYCIN B TO STREPTIDINE, STREPTOBIOSAMINE AND D-MANNOSE Sir :
Streptomycin B1has been degraded to derivaI n addition, however, we have prepared N,Ndimethyl - N' - (2 - pyridyl) - N' - ( 5 - bromo - 2- tives of streptidine, streptobiosamine and D-mantheny1)-ethylenediamine (I, X = Br) and N,N- nose. I t appears t o be a triacidic base of the formdimethyl - N ' - (2 - pyridyl) - N' - (5 - chloro - 2- ula C27H49017N7. Methanolysis of streptomycin B with 1.3 &V theny1)-ethylenediamine (I, X = Cl). In tests using the isolated guinea pig ileum, these halogen- methanolic hydrogen chloride for five days a t room ated compounds were more active than Pyribenz- temperature followed by acetylation afforded amine. Preliminary tests in animals indicate that methyl tetraacetyl streptobiosaminide dimethyl they have a t least twice the antihistamine activ- acetal,2 m. p. 124-125O (cor.); [ a I z 5 D -122' (c, ity, twice the duration of action, and one-half the 0.56 in chloroform) and a-methyl tetraacetyl Drnannopyranoside, m. p. 65-66' (cor.) unchanged acute toxicity of Pyribenzamine. These compounds were prepared by the reaction on admixture of an authentic specimen; [ c Y ] ~ ~ D of 5-bromo-2-thenyl chloride and 5-chloro-2-thenyl + N o (c, 1.1 in chloroform). chloride with N,N-dimethyl-N'-(2-pyridyl)-ethyl- Anal. Cakd. for C16H2201~1:C, 49.72; H, 6.12; ened'iamine.2s4 5-Bromo-2-thenyl chloride, b. p. OCH3, 8.56; CH3C0, 47.5. Found: C, 50.01; 82-83' at 1 mm., was obtained in 70-8070 yield H , 6.08; OCH3, 8.98; CH3C0, 4'7.7. from the chloromethylation of 2-bromothiophene Treatment of streptomycin B with ethylmerby the method used previously with thiopheneP captan and concentrated hydrochloric acid for A n d . Calcd. for C6H4BrClS: C1, 16.8. Found: eighteeh hours a t room temperature and subseC1 (by hydrolysis), 16.97,. 5-Chloro-2-thenyl quent acetylation of the vacuum-dried residue afchloride, b. p. 67-68' a t 1 mm., was prepared forded streptidine octaacetate, m. p. 255-257' similarly by the chloromethylation of 2-chloro- (cor. dec.), 0-thioethyl tetraacetyl streptobiosamthiophene. Anal. Calcd. for CsH~C12S:C1 (by inide diethyl m e r ~ a p t a l m. , ~ p. 112-113' (cor.); hydrolysis), 21.293. Found: C1, 21.1. [ C Y ] ~ -30" ~D (c, 0.95 in chloroform), and two isoThe condensation of 5-bromo-2-thenyl chloride meric thioethyl tetraacetyl hexosides: .I,m. p. and N,N -dimethyl - N' - (2-pyridyl) - ethylenedi- 107-10s' (cor.), [ a l Z 5+94' ~ (c, 1.06 in chloroamine using sodium2 or potassium amide gave form); and B, m. p. 161-162' (cor.), [CY]"D -67' N,N - dimethyl - N ' - ( 2 - pyridyl) - N' - (5- (c, 0.51 in chloroform). bromo - 2 - thenyl) - ethylenediamine (I, X = Br), Anal. Calcd. for C16H2409S: C, 48.98; H, 6 . l i ; yield. The S, 8.16; CH3C0, 43.M; mol. wt., 392.4. Found b. p. 173-175' a t 1 mm., in monohydrochloride melted a t 124-126O. Anal. forA: C,48.91; H, 6.04; S, 8.17; CH3CO,44.2; Calcd. for C14HISBrCIN3S:C, 44.6; H, 5.1; N, mol. wt. (Rast), 378. Found for B : C,49.16; 11.1; S, 8.5. Found: C, 44.9, 44.8; H, 5.3, 5.1; H , 6.28; S, 6.41; CH&O,43.3. N, 11.0, 11.0: S, 8.7, 8.6. N,N-Dimethyl-N'The hitherto undescribed p-thioethyl tetraace(1) A. W. Weston, THIS JOURNAL, 69,980 (1947). tyl D-mannoside was prepared from D-mannose by (2) Huttrer, Djerassi, Beears, Mayer and Scholz, ibid., 68, 1999 (1946). (3) Litchfield, Goddard, Adams and Jaeger, Bull. Johns Hopkins Hosp., in press. (4) Whitmore, Mosher, Goldsmith and Rytina, THISJOURNAL, 67, 393 (1945). (5) Blicke and Leonard, i b i d . , 68, 1934 (1946).
(1) Paper I V of this series: J. Fried and E. Titus, J . Bioi. Chern., 168, 301 (19117). ( 2 ) S . G. Brink, F. A. Kuehl, Jr., and K. Folkers, S c i p n c p , 102, 506 (1946). (3) I. R . Hooper, L. H. Klemm, W. J. Polglase and M. L. Wolfram, Txrs JOURNAL, 68, 2120 (1946).
