BSO J. H. CLAIIK,J. P.ENGLISH, G. R.JANSEN, H. W. MARSON, AI,LI.ROGERS A N D W. E. TAFT Vol. 80 [CONTRIBUTION FROM
THE
ORGANIC CHEMICAL RESEARCH SECTION,PEARL RIVER LABORATORIES, RESEARCH DIVISION AMERICAN CYANAMID Co. ]
3-Sulfanilamido-6-alkoxypyridazinesand Related Compounds BY J. H. CLARK, J. P. ENGLISH, G. R. JANSEX, H. W. MARSON, >34. !I. ROGERS AND W. E. TAFT RECEIVED SEPTEMBER 19, 1957
3-Sulfanilamido-6-chloropyridazinewhen reacting with the sodium derivatives of various alcohols or phenol gave the corresponding ethers. Related derivatives of 3-sulfanilarnido-4- and 5-methylpyridazine also were prepared. 3-Sulfanilamido-6-methoxypj.ridazine is of the greatest interest because of its high antibacterial activity and slow excretion.
Recent developments in pyridazine chemistry have made rather readily available the hitherto difficultly prepared 3-sulfanilamidopyridazine (IV) . Maleic hydrazide (I) is readily converted by the action of phosphorus oxychloride into 3,6-dichloropyridazine (II).2s3This reactive intermediate can
1CH=CH \ o=c c-0
POC1, ___f
111
CHaOH + NaOCH3 -xF-+
I. atives of the corresponding alcohols or phenol. The reaction conditions and yields are, in most cases, based on a single run and are probably not optimal. For the methyl homolog it was found that temperatures and times below those given resulted in incomplete reaction while higher temperatures gave a reaction mixture which was quite difficult to purify. T w o methyl homologs of 3-sulfanilamido-Gchloropyridazine were obtained by the reaction of 3,6-dichloro-4-1~~ethylpyridazine~ with sulfanilamide. CH3
I \'
be converled iiito 3-sulfanilamido-6-chloropyridazine (111) by fusion with sulfanilamide and potassium ~ a r b o n a t e . ~ - jThe catalytic dehalogenation of this compound gives 3-sulfanilamidopyridazine (IV).3,5,6A longer synthesis of I V through 3aminopyrida~ine~ also has been reported. Re-evaluation of the bacteriology and pharinacology of the latter compound gave results of sufficient interest to suggest the study of other sulfanilamidopyridazines such as those derivable from 3-sulfanilarnido-6-chloropyridazine(111) and certain of its homolog^.^,^ The reaction of 111 with sodium iiiethoxide in methanol a t 120" in an autoclave gave 3-sulfanilamido-G-iiiethoxypyridazirie (V). l o Table I lists this coinpound and seven other ethers similarly obtniiietl by thc reactioii of TIT with the sotliuili clvriv(1) 1'. S. \Viniiek and I
