Synthesis and structures of 5(3H)-oxotetrahydro-1H-imidazo[4,5-c][1,2,5]thiadiazole 2,2-dioxides

Abstract

The reactions of sulfamides with 4,5 dihydroxyimidazolidin 2 ones were studied at ambient and high pressure. The previously unknown derivatives of 5(3H) oxotetrahydro 1H imidazo [4,5 c] [1,2,5]thiadiazole 2,2 dioxide, viz., sulfo analogs of tetrahydroimidazo[4,5 d]imidazole 2,5 (1H,3H) diones (glycolurils), were synthesized. The structures of some of these compounds were established by X ray diffraction. The high pressure reactions performed under conditions of solvent phase transitions afforded also N (1,3 diethyl 5 hydroxy 2 oxoimidazolidin 4 yl) N,N´ dialkylsulfamides. Among these compounds, a new conglomerate was found. Key words: α ureidoalkylation, 5(3H) oxotetrahydro 1H imidazo[4,5 c][1,2,5]thiadiazole 2,2 dioxides, N (1,3 diethyl 5 hydroxy 2 oxoimidazolidin 4 yl) N,N´ dialkylsulfamides, X ray diffraction study, conglomerate.Imidazolidin 2 one derivatives exhibit antispasmodic, analgesic, neurotropic, etc. activities. 1-4 Substituted 1,2,5 thia diazolidine 1,1 dioxides inhibit the enzymes human leu kocyte elastase and cathepsin G and have antiulcer and antispasmodic activities. 5-7 Hence, the design of potent biologically active compounds containing the annulated imidazolidine and thiadiazolidine rings continues to be an important problem.Earlier, we have shown for some examples that the simplest procedure for the synthesis of such compounds is based on the condensation of 4,5 dihydroxyimidazolidin 2 ones (DHIs) 1 with sulfamides. 8-11 First representatives of 1,3,4,6 tetraalkyl 5(3H) oxotetrahydro 1H imidazo [4,5 c][1,2,5]thiadiazole 2,2 dioxides 2a,b were synthe sized in 52% and 8% yields, respectively, in water at pH 1, atmospheric pressure, and 80-90 °C. 8,9 Under these con ditions, unsubstituted sulfamide gives 4,4´ sulfonyl diiminobis(1,3 dialkylimidazolidin 2 ones) 3a,b in 40-45% yields. 9,10 Tetrahydroimidazothiadiazoles 2c,d were synthesized in 45-63% yields by condensation of 1a,b with unsubstituted sulfamide at pH 5-6 and 60 °C. 8 More recently, 12 we have found that the acid catalyzed reac tions of 1 alkylsulfamides with DHIs in methanol afford compounds containing the imine bond, viz., 1,3 dialkyl 4 (alkylaminosulfonylimino)imidazolidin 2 ones 4a-h.In continuation of our studies aimed at extending the range of potent biologically active monosulfo analogs of glycolurils 2 containing different numbers of alkyl sub stituents at the nitrogen atoms, here we report a compre hensive study of the condensation of 1a-d with sulfamides 5a-f at ambient and high pressure and the structural investigations of the resulting compounds by different physicochemical methods, including X ray diffraction.Under atmospheric pressure, the reactions of 1a-d with sulfamides 5a-f were carried out at 80-90 °C and pH 1 in water for 0.5-1 h (conditions A), at 60-70 °C in H 2 O at pH 6 (conditions B), or in MeOH both in the presence of acids (conditions C) and in their absence (conditions D) (Scheme 1). In addition, analogous reac tions were studied at high pressure using different modes.Di N substituted tetrahydroimidazothi...

α-Thioureidoalkylation of urea heteroanalogs

“…1-5 α Ureidoalkylation of thiosemicarbazide, aminoguanidine, and sulfamides yielded 5,7 dialkyl 3 thioxoperhydroimidazo [4,5 e] [1,2,4]tri azin 6 ones (1), 2 4,5 bis(thiosemicarbazido) and 4,5 bis (guanidinoamino)imidazolidin 2 ones (2, 3), 2 4 (guani dinoamino) and 4 (sulfonylimino)imidazolidin 2 ones (4-6), 2-4 and 5(3H) thioxotetrahydro 1H imidazo [4,5 c] [1,2,5]thiadiazole 2,2 dioxides (7). 5 Only few examples of the synthesis of glycoluril heteroanalogs by condensation of ureas with 4,5 dihydroxy imidazolidine 2 thiones (DHIT) have been published. 6,7 The present work is devoted to α thioureidoalkylation of urea heteroanalogs (thiosemicarbazide, aminoguani dine, sulfamide, and sulfonamides) with DHIT 8a-c and development of the synthetic methods towards novel imidazolidine 2 thione derivatives.…”

“…It is known that the spontaneous sepa ration occurs provided the crystal of the corresponding compound contained homochiral molecule associates 14 formed preferably by strong hydrogen bonds. 5 Therefore, it was of interest to find whether this cation cation pattern remained on going from the C=O group to the C=S group that forms the hydrogen bonds that differ from those with the carbonyl group in the number and strength. 17, 18 Analysis of the geometry of dication 13b indicated that replacement of the oxygen atom by the sulfur atom resulted in the insignificant lengthening of the C(2)-N bonds (the difference did not exceed 0.03 Å) and in the change in the heterocycle conformation from the flat tened twist to the envelope (mean deviation of the C(5) atom is 0.24 Å).…”

The new synthesis of sulfuryl-bridged triazinane and its selective recognition to SO42−

“…The synthesis of 1 (tetrahydro-1H-imidazo[4,5-c][1,2,5]thiadiazol-5(3H)-one 2,2-dioxide) was performed analogously according to a published report [30]: To a solution of sulfonamide (0.48 g, 5.0 mmol) in 8 mL dilute hydrochloric acid solution (pH = 6), L1 (0.59 g, 5.0 mmol) was added. The resulting mixture was heated to 60 °C and kept stirring for 12 h. After the reaction was completed, the reaction solution was cooled to 0 °C, and white solids (2) were precipitated, the yield is 0.62 g (69.6%).…”

The synthesis, structure, and electron density distribution in crystals of 4,5-dihydroxyimidazolidine-2-thiones

“…4,5 Dihydroxyimidazolidine 2 ones (DHI) are wide ly used as building blocks for the synthesis of various het erocyclic compounds, in particular, tetrahydroimidazo [4,5 d]imidazoles, 1-6 octahydroimidazo[4,5 e] 1,2,4 tri azines, 7,8 and tetrahydroimidazo[4,5 с] 1,2,5 thiadi azoles. 9, 10 The use of thio analogs of DHI, i.e., 4,5 dihydroxyim idazolidine 2 thiones (DHIT), in the synthesis of the cor responding heterocyclic systems is less studied because these compounds are less available. Among DHIT, those containing various aryl substituents at the N(1), N(3), C(4), and C(5) atoms have been studied the best.…”

“…9, 10 The use of thio analogs of DHI, i.e., 4,5 dihydroxyim idazolidine 2 thiones (DHIT), in the synthesis of the cor responding heterocyclic systems is less studied because these compounds are less available. Among DHIT, those containing various aryl substituents at the N(1), N(3), C(4), and C(5) atoms have been studied the best.…”