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

Abstract

4,5 Dihydroxyimidazolidine 2 thiones were synthesized and their structural peculiarities were studied. A comparative analysis of dihydroxyimidazoli dine 2 thione and its carbonyl analog performed in the framework of detailed investigation of the electron density distribution in the corresponding crystals revealed the reason for different number and geometric parameters of the hydrogen bonds formed by the (thio)carbonyl groups in the crystals.Key words: cis and trans isomers, 4,5 dihydroxyimidazolidine 2 thiones, 1 Н and 13 С NMR spectroscopy, X ray analysis, electron density distribution function, topological analysis. 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. 11-14 They are synthesized under conditions of both base and acid catalysis. The most widely used method of synthesis of DHIT is the base catalyzed coupling of thioureas with α dicarbonyl compounds. 12-14 Acid catalysis was em ployed in the reaction of unsymmetrically substituted α dicarbonyl compounds with thiourea or 1,3 dimethyl thiourea. 15 A few examples of the coupling of 4,5 dihydroxy imidazolidine 2 thione (1а) with ureas for the synthesis of hetero analogs of glycolurils (tetrahydroimidazo [4,5 d]imidazole 2,5 diones) were described; however, no data on the method of synthesis and on the yield and melting point of this compound are available. 16 The structure of DHIT has virtually not been discussed in the literature. 17 To develop synthetic routes to new 4,5 dihydroxyimi dazolidine 2 thiones and to perform a detailed study of their structure, in the present work we studied the cou pling of thioureas with glyoxal and analyzed the structure of reaction products by NMR spectroscopy, chtomato mass spectrometry, and X ray diffraction analysis (includ ing detailed examination of the electron density distribu tion in the crystal).The synthesis of DHIT 1а-c from glyoxal and thio ureas 2а-c (Scheme 1) was studied under the conditions similar to those reported earlier 3,18,19 for DHI. The effect of temperature (20-90 °С), reaction time (0.5 to 7.5 h), and рН of the medium (pH 3-9) on the yields of the target DHIT were investigated. It was found that com pound 1а is formed in 47-50% yield after 30 min at рН 4 and 50 °С unlike related DHI, 3 which is prepared at рН 6.5-7.5 and 90 °С. Compounds 1b,c were obtained in 75-78 and 60-63% yields, respectively, after 2 h at рН 5-6 and 50 °С analogously to 1,3 diethyl DHI, which was obtained under identical conditions, but after 7 h. 19

α-Thioureidoalkylation of urea heteroanalogs

“…Similar results have previously been ob served in 4,5 dihydroxyimidazolidine 2 thione and its oxo analog. 19 The difference in the bond lengths of aminoguanidine fragments for compounds 13b and 3 (R = Me) is on average 0.005 Å. Although the replace ment of the C=O group by the thiocarbonyl group in compound 13b does not affect the dication geometry, this compound crystallized as a racemate (space group Pbca), which is obviously due to the influence of the environ ment.…”

Reaction Pathway and Kinetic Study of 4,5-Dihydroxyimidazolidine-2-thione Synthesis by HPLC and NMR

“…7 Thiourea interaction with glyoxal in the presence of water-soluble alcohol mainly produces a mixture of cis-and trans-DHIT isomers and urea and 2-thioimidazole are formed as byproducts. 1,8 As known, a bicyclic product, 1,4-diaza-3,6-dithiabicyclo[3.3.0]octane-2,5-diimine, is formed in strongly acidic conditions. 9 However, no experimental confirmation of the formation of byproducts has been presented, and the pathway for the origin of the impurities is unclear.…”

“…4,5-Dihydroxyimidazolidine-2-thione (DHIT) is a heterocyclic compound formed by the interaction of thiourea with glyoxal (Figure 1). 1…”

Synthesis and Structure of 1-Substituted Semithioglycolurils

“…32 4,5-Dihydroxyimidazolidine-2-thione was synthesized by the condensation of thiourea with 40% aq glyoxal. 41 Thioglycolurils 1a-m,o,p; Approach 1 4,5-Dihydroxyimidazolidine-2-thione (4; 0.40 g, 3.0 mmol) and the appropriate urea 2a-m,o,p (2.5 mmol) were suspended in H 2 O (10 mL). Aq HCl (35%, 0.08 mL) was added, and the solution was heated to 76-80 °C and stirred for 30 min.…”