Cyclothiomethylation of aryl hydrazines with formaldehyde and hydrogen sulfide

Abstract

Cyclothiomethylation of phenyl hydrazine with CH 2 O and H 2 S in a ratio of 1 : 3 : 2 in an acidic medium (HCl) afforded previously unknown 3 phenyl 1,3,4 thiadiazolidine (35% yield) and N phenyl(perhydro 1,3,5 dithiazin 5 yl)amine (35% yield). The analogous reaction in an alkaline medium (BuONa) produced N phenyl(perhydro 1,3 thiazetidin 3 yl)amine (22% yield). The reaction of 1,2 diphenyl hydrazine with CH 2 O and H 2 S in an alkaline medium gave 1,2,4,5 tetraphenylhexahydro 1,2,4,5 tetrazine and previously unknown 3,4 diphenyl 1,3,4 thiadiazolidine and 5,6 diphenyltetrahydro 1,3,5,6 dithiadiazepine in 39 and 22% yields, respectively. Cyclothiomethylation of benzyl hydrazine afforded previously unknown bis[(6 benzyl 4,2,6 thiadiazolidin 2 yl)methyl] sulfide (60% yield) and N ben zyl(perhydro 1,3,5 dithiazin 5 yl)amine (19% yield). The reaction of tosyl hydrazine produced 3 [(p tolyl)sulfonyl] 1,3,4 thiadiazolidine, N (perhydro 1,3,5 dithiazin 5 yl) p tolylsulfonamide, and 3,7 bis(p tolylsulfonylamino) 1,5 dithia 3,7 diazacyclooctane in 21, 38, and 41% yields, respectively.Earlier, 1 we have performed cyclothiomethylation of hydrazine with formaldehyde and hydrogen sulfide and prepared annelated 1,3,4 thiadiazolidines and 1,3,5 thia diazines. According to the available data, 2-4 1,3,4 thia diazole derivatives have found wide use as antibacterial and antiviral agents and as inhibitors of oxidation of cya nine dyes and metal complexing agents. 5 N Phenyl sub stituted nitrogen containing heterocycles, in which the N atoms are conjugated with chromophoric groups, are of particular interest as photosensitive and photocontrolled molecular devices. 6 The present study is a continuation of investigations on cyclothiomethylation of amines with CH 2 O and H 2 S. 7-9 Another aim was to develop efficient methods for the synthesis of aryl substituted thiadiazoles. The latter com pounds are of practical interest. We examined thio methylation of phenyl, 1,2 diphenyl, benzyl, and tosyl hydrazines with the H 2 S-CH 2 O system under neutral, acidic, and alkaline conditions. Results and DiscussionRecently, 10 we have found that the thiomethyla tion pathway of hydrazine with CH 2 O and H 2 S strongly depends on the starting component ratio, the heterocyclization temperature, and pH of the reaction mixture.In the present study, we examined cyclothio methylation of phenyl hydrazine hydrochloride (1•HCl) with CH 2 O and H 2 S in a ratio of 1 : 3 : 2 at pH 0.45-0.50 (method A). It was found that the reaction performed at 0 °C selectively produces 3 phenyl 1,3,4 thiadiazol idine (2), whereas N phenyl(perhydro 1,3,5 dithiazin 5 yl)amine (3) and 6 phenylperhydro[1,3,4]thiadiazi no [5,4 d] [1,3,5]dithiazine (4) are generated along with compound 2 at higher temperature (20-70 °C) (Scheme 1). At 70 °C, the amount of minor product 4 derived under these conditions from compound 3 is at most 8%.

Synthesis, crystal structure, and interconversions of new N-aryl-1,3,5-dithiazinanes, 1,3,5-thiadiazinanes, and 1,5-dithia-3,7-diazacyclooctanes

“…In the 1 H NMR spectra of eight membered dithiadiazacyclooctanes, the methylene pro tons, in contrast to dithiazinanes and thiadiazinanes, are found as doublets of doublets (δ H 4.86-5.29), that indi cates decelerated inversion of the cyclooctane ring in solution. 13, 14 In the 13 C NMR spectra, the singlet methyl ene signals are found in the region δ 55.9-56.4…”

“…Compound 4c was isolated by fractional crystallization, 4a,b,f,l by column chromatography (SiO 2 , benzene-C 2 H 5 OH, 9 : 1), 4d,g were filtered off and washed with ethanol. 13 C NMR (22.5 MHz), δ: 53.4 (t, C(2), C(6)); 69.3 (t, C(4)); 117.6 (d, C(18), C (14), C(12), C(8)); 120.3 (d, C(16), C(10)); 128.8 (d, C(17), C(15), C(11), C(9)); 147.4 (s, C (7) (18), J = 6.5 Hz); 7.31 (d, 4 H, C(9)H, C(11)H, C(15)H, C(17)H, J = 6.5 Hz). 13 C NMR (22.5 MHz), δ: 53.8 (t, C(2), C(6)); 69.7 (t, C(4)); 113.4 (s, C(10), C(16)); 119.7 (d, C(8), C(12), C (14), C(18)); 132.3 (d, C(9), C(11), C(15), C(17)); 147.9 (s, C(7), C (13) …”