149%
COMMUNIClTIONS
time in coilsideration of the continued activity in the dihalocarbene area, particularly the interesting studies concerning the use of dihalocyclopropane compounds in the synthesis of allenesg and highly strained tricyclic systems.1° Our studies, directed in particular at the preparation of other carbenes by the polyhalomethylmercurial route, are continuing, and details will be reported at a later date. Acknowledgment. The authors are grateful to the U. S. Army Research Office (Durham) for support of this work.
CzH3--SO:!
VOL.
N
27
NHz 4
~ I1 JCOOC,H,
CHa-0
N NHz yJCOOCZH6
-+I
I11 N303:C, 48.7; H, 5.6; N, 21.3. Found: C, 48.8;
H, 5.8; N,21.6). Compound 111 was then reduced by lithium aluminum hydride in anhydrous ether to give, after recrystallization from methanol, a DEPARTMENT OR CHENISTRY DIETM.4R SEYFERTH 60% yield of 2-methoxy-4-amino-5-hydroxymethylMASSACHUSETTS INSTITUT~ OF JAMES M. BURLITCH pyrimidine (I) which melted between 173-174' t o TECHNOLOGY JAMES K. HEEREN a yellow liquid (Calcd. for CeH9N302:C, 46.4; H, CAMBRIDGE 38, Mass. 5.9; N, 27.1. Found: C, 46.5; H, 6.2; N, 27.1). Received January 26, 1962 The synthetic product I exhibited the following (9) (a) W.von E. Doering and P. AI. LaFlamme, Tetra- ultraviolet absorption: Xfn1I: 227 mp (E 7600), 271 hedron, 2, 75 (1958). (b) W. R. Moore and H. R. Ward, J . mp (E 7300); " ; , ' : X : 229 mp (E 8400), 261 mp ( E Org. Chem., 25, 2073 (1960). (c) L. Skattebol, Tetrahedron 9500); A", ? NaoH 231 mp ( E 6200), 271 mp (E 7600). Letters, 167 (1961). ( d ) T. J. Logan, ibzd., 173 (1961). (10) W.R. PIIoore, H. R. Ward, and R. F. Merritt, J . Am. Its infrared absorption spectrum in Nujol posCheni. SOC.,83, 2019 (1961). sesses identical bands with that of the antibiotic reported in the literature.? Furthermore, the R , values (at 25O, descending) of bacimethrin4 and Synthesis of Bacimethrin' our synthetic compound in 3% ammonium chloSir: ride are 0.86 and 0.86, respectively; and in butanol Tanaka and eo-workers? have recently isolated (saturated with ammonia) are 0.62 and 0.61, a new antibiotic, bacimethrin, produced by Bacillus respectively. Thus, we confirmed the previous megatherium from a soil sample collected in Japan. assigned structure I for that antibiotic. The striking structural similarity of bacimethrin This antibiotic is active against various yeasts and some bacteria.2 Its biological activity is to the known biologically active HMC (5-hydroxymarkedly decreased by the presence of vitamins methylcy tosine), toxopyrimidine (2-methy l-4-amino-5-hydro~ymethylpyrimidine),~~~ methioprim (2B1 and Bo. Based on degradation studies, the structure of methylthio - 4 - amino 5 - hydroxymethylpyrimias well as Bayer DG-428 (2-[o-chlorothis antibiotic has been proposed as 2-methoxy-4amino-5-hydroxymethylpyrimidine(I).* This type benzylthio ]-4-dimethylamin0-5-methylpyrimidine)~ suggests that compound I merits further study in CHJ-0 K NH2 various biological systems.
-
'ACH20H I
of 2-methoxypyrimidine has not been reported previously in the literature. We now wish to report that, in connection with our current investigation on 2-methoxypyrimidines for antimetabolite and antivitamin studies, we have synthesized I via the following sequence of reactions : 2-Ethylsnlf onyl-4-amino-5-carbethoxypyrimidine (11), prepared by the method of Sprague and Johnson13was treated with sodium methoxide in absolute methanol a t 5' to give 2-methoxjr-4amino-5-carbethoxypyrimidine (111), m.p. 151153' (from benzene) in 76% yield (Calcd. for CgHll(1) This study mas made possible under the auspices of thp Cancer C'hemotherapy National Service Center of the ?intimal Cancer Institute, National Institutes of Health, Public Health Service, Contract Xo. SA43-ph-3025. ( 2 ) F. Tiinaka, S. Tnkenchi, S . Tnnaka. H. Yonehara, H . I'niezn~nx, and Y. Sniniki, J . =1ntzbiotics, Ser. -4.14, I61 (1961). ( 3 ) J. 11.P p r n g w and T. B. Johnsou, ,J. Am. Chem. Suc., 57, 2254 (1935).
HENRYc. KOPPEL MIDWEST RESEARCH INSTITUTE ROBERTHENRYSPRINGER ROLAND K. ROBINS
KANSASCITY 10, hlo.
C.
c. CHENa
Received January 31, 1962 (4) This comparison was made possible by an authentic sample of bacimethrin kindly provided by Drs. F. Tanaka and H . Yonehara of the Institute of Applied Microbiology, the Universitjr of Tokyo, Tokyo, Japan, to whom sincere thanks are due. ( 5 ) (a) G. R. Wyatt and S.S. Cohen, Nature, 170, 1072 (1952). ( b ) G. R . Wyatt and S. S.Cohen, Biochem. J . , 5 5 , i74 (1953). (c) A. Ilornow and G. Petsch, Ann., 588, 45 (1954). ( d ) C. S Rliller, J . Am. Chem. SOC.,77,752 (1955). (6) (a) R. Abderhalden, Arch. ges Physiol., 240, 647 (1938); zbzd., 242, 199 (1939). (b) A. Watanabe, J . Pharm. SOC.Japan, 59, 133 (1939) (c) K. Makino, T. Kinoshita, T. Sasaki, and T, Shioi, Nature, 173, 34 (1954); zbid., 174, 275, 1056 (1954). (d) R. Guthrie, M. E. Loebeck, and M. J. Hillman, Proc. SOC.Exptl. Biol. M e d . , 94, 792 (1957). (e) RI. Kawashima, J . Pharm. Soc. Japan, 77, 758 (1957) ( f ) A. Schellenberger and I
