Glyconothio‐O‐lactones. Part III. Thermolysis of a 4,5‐Dihydro‐1,2,3‐ and a 2,5‐Dihydro‐1,3,4‐thiadiazole

Abstract

Addition of CH,N, to 2,3: 5,6-di-O-isopropylidene-l-thio-mannono-l,4-lactone (1) gave the 2,5-dihydro-1,3,4-thiadiazole 2 and the 4,S-dihydro-1,2,3-thiadiazole 3. First-order kinetics were observed for the thermolysis of 3 (Scheme2) at XO-110" in C,D,CI solution and of 2 (Scheme3) at 20-35" in CDCI,, respectively. The 1,2,3-thiadiazole 3 led to mixtures of the thiirane 9, the starting thionolac1.one 1, the thiono-1,s-lactone 8, and the enol ether 7, while the isomeric 1,3,4-thiadiazole 2 led to mixtures of the anomeric thiiraiies 9 and 12. the 0-hydrogen S,O,O-ortholactone ci-0-14, the S-methyl thioester 15, the S,:S,O-ortholactone 13, and the 2 3 : 5,G-di-0-isopropylidene-mannono-I ,4-lactone (16). Pure products of the thermolysis were isolated by semipreparative supercritical fluid chromatography (SFC), whereas preparative HPLC led to partial or complete decomposition. Thus, the /h-mannofuranosyl b-o-mannofuranoside 10, contaminated by an unknown S species, was isolated by preparative HPLC of the crude product of thermolysis of 3 at 115-120" and partially transformed in CD,OD solution into the symmetric di(a-o-mannofuranosyl) tetrasulfide 11. Its structure was evidenced by X-ray analysis. Similarly, HPLC of the thermolysis product of 2 gave the enethiol 17, the sulfide 19, and the mercapto alcohol 18 as secondary products. Thermolysis of the thiirane 9 at 110-120" (Scheme 4) led to the anomeric thiirane 12 which was transformed into mixtures of the enethiol 17 and the enol ether 7. Addition of H,O to 17 and 7 gave the corresponding heniiacetals 18 and 20. The mechanism of the thermo1,ysis of the dihydrothiadiazoles 2 and 3, and the thiiranes 9 and 12 is discussed.

Thioglucose-derived tetrasulfide, a unique polysulfide model compound

“…1 , OAc-TGS4 crystallized in the monoclinic space group, C 2 , with half of the tetrasulfide molecule present in the asymmetric unit. Consistent with other linear tetrasulfides [ 14 ], the central S–S fragment features a longer distance and smaller dihedral angle [i.e., sulfane–sulfane; S(2)–S(2)’: 2.0516(12) Å, S(1)–S(2)–S(2)’–S(1)’: 82.5(1)°] than the proximal S–S fragment [i.e., sulfane–sulfide; S(1)–S(2): 2.0346(10) Å, C(1)–S(1)–S(2)–S(2)’: 91.6(1)°]. Similarly, the central S–S fragment of OAc-TGS4 is ∼0.02 Å longer than that of the corresponding acetate-protected glucosyl disulfide, OAc-TGS2 ( Fig.…”

Supercritical Fluid Chromatography and Extraction

“…In the preparative chromatography of pharmaceutical agents or their precursors, where residual solvent or solvent impurities can be an issue, CO 2 can be an even more attractive alternative as a mobile phase. Bernet et al illustrated this point as they studied the thermolysis of dihydrothiadiazoles (205). They isolated pure thermolysis products using semipreparatory pcSFC, while preparative HPLC resulted in partial or complete decomposition.…”