α-Thioureidoalkylation of urea heteroanalogs

Abstract

α Thioureidoalkylation of urea heteroanalogs such as thiosemicarbazide, amino guanidine, sulfamide, and sulfonamides with 4,5 dihydroxyimidazolidine 2 thiones has been studied. Previously unknown 4,5 bis[thiosemicarbazido(guanidinoamino)]imidazolidine 2 thiones, 5,7 dialkylperhydroimidazo[4,5 e] [1,2,4]triazine 3,6 dithiones, 4,6 diethyl 5(3H) thioxotetrahydro 1H imidazo[4,5 c][1,2,5]thiadiazole 2,2 dioxide, and 1,3 dialkyl 4 [guanidinoimino(arylsulfonylimino)]imidazolidine 2 thiones have been synthesized. Key words: α thioureidoalkylation, thiosemicarbazide, aminoguanidine, sulfamide, 4,5 dihydroxyimidazolidine 2 thiones, 4,5 bis[thiosemicarbazido(guanidinoamino)]imidazol idine 2 thiones, 5,7 dialkylperhydroimidazo[4,5 e][1,2,4]triazine 3,6 dithiones, 4,6 diethyl 5(3H) thioxotetrahydro 1H imidazo[4,5 c][1,2,5]thiadiazole 2,2 dioxide, 1,3 dialkyl 4 [guanidinoimino(arylsulfonylimino)]imidazolidine 2 thiones.α Ureidoalkylation of ureas and their analogs with 4,5 dihydroxyimidazolidin 2 ones have been carefully studied in our laboratories. 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. 6,7The 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.Thioureidoalkylation of thiosemicarbazide with DHIT 8a-c under conditions described previously 2 for the syn thesis of compounds 2 (water, pH 2, 80 °C, DHIT : thio semicarbazide = 1 : 2) resulted in 4,5 bis(thiosemi carbazido)imidazolidine 2 thiones 9a-c in 70-75% yields and perhydroimidazo[4,5 e][1,2,4]triazine 3,6 di thiones 10a-c (Scheme 1). Imidazotriazines 10b,c were isolated in 5-15% yields. Together with signals of the main product 9a, the signals that were attributed to com X = S (2), NH 2 + Cl -(3)pound 10a (4.94 and 5.25 (both d, each 1 H, CH-CH, J = 8.5 Hz); 5.69 (br.s, 1 H, NH); 7.29 (br.s, 2 H, 2 NH);

Hetero‐Bambusurils

“…[28] We investigated the reaction between thiourea and glyoxal (2 : 1 ratio) under milder basic or neutral conditions at ambient temperatures or using ultrasonic irradiation. [30] Considering the reports on the preferred reactivity of ethers in similar reactions, [31] we converted 1 b to the corresponding diether, trans-1 c, by treating 1 b with slightly acidic methanol. All efforts to react 1 b with either thiourea or urea under various conditions resulted in the above described product mixture.…”

α-Thioureidoalkylation of functionally substituted ureas: II. Synthesis of thio analogs of N-hydroxyalkyl-1,5-diphenylglycolurils

“…We recently initiated a series of studies aimed at synthesizing glycoluril thio analogs [1,14]. In the present communication we report on the reaction of N-(hydroxyalkyl)ureas IIa-IIe (ureido alcohols) with 1,3-dialkyl-4,5-dihydroxy-4,5-diphenylimidazolidine-2-thiones Ia and Ib as a method of synthesis of 1-hydroxyalkyl-3a,6a-diphenyl-5-thioxooctahydroimidazo-[4,5-d]imidazol-2-ones III (thio analogs of N-hydroxyalkyldiphenylglycolurils).…”

α-Thioureidoalkylation of 4-alkyl- and 4-phenylthiosemicarbazides

“…We have previously studied the -thioureidoalkylation reaction of a thiosemicarbazide to give the 1,3-dialkyl-4,5-bis(thiosemicarbazido)imidazolidine-2-thiones 1a,b and the 5,7-dialkylperhydroimidazo[4,5-e]-1,2,4-triazine-3,6-dithiones 2a,b [8]. In this work we have now studied the reaction of the 4-alkyl-and 4-phenylthiosemicarbazides 3a-d with the 4,5-dihydroxyimidazolidine-2-thiones 4a,b and the effect of the substituent at position 4 of the thiosemicarbazide 3 on the reaction routes and yields.…”

“…The highest yields of the 1,3-dialkyl-4,5-bis(4-alkyl(phenyl)thiosemicarbazido)imidazolidine-2-thiones 5a-h (70-82%) were achieved by carrying out the reaction at 70-80ºC for 2 h. At lower temperature over 24 h the reaction mixture contains about 40% of the unreacted initial 3a-d and 4a,b materials. At 90ºC the dihydroxyimidazolidinethiones 4a,b give 30-35% of 1,3-dialkyl-2-thioxoimidazolidin-4-ones (thiohydantoins [8]) and this leads to a lowering of the yields of compounds 5a-h. In addition to the derivatives 5a,b the reaction of compounds 4a,b with the thiosemicarbazide 3a also gives the imidazotriazines 6a,b in 2-5% yields.…”

“…Hence the nature of the substituent at position 4 of the thiosemicarbazide does not appear to have a major effect on the reaction product yields for 5a-h, being little lowered upon lengthening or branching the alkyl chain at position 4 of the starting thiosemicarbazide (Table 1). We have previously obtained the imidazotriazines 2a,b (unsubstituted on the N(4) atom) in 5-15% yields [8]. The yield of the 4-substitued imidazotriazines 6 is lower.…”