Bicyclic bisureas, especially 2,4,6,8-tetraazabicyclo[3.3.0.]octan-3,7-dione (glycoluril), have a special place in chemistry of heterocyclic compounds. The carbamide fragment in glycoluril structure determines the properties of the molecule, which are due to the presence of two reaction centers (NH-groups and C=O-groups) in the molecule. In this work, we analyzed the proton and carbon chemical shifts of glycoluril and its derivatives (86 compounds) in the NMR spectra to reveal the effect of the donor-acceptor substituents on the changes in the electron density in the bicyclic framework from the position of symmetry and asymmetry. A general analysis of the 1H and 13C NMR spectra of glycolurils makes it possible to accurately determine the spatial configurations of molecular symmetry, in the presence of which (σ1 and / or σ2) the enantiotopic hydrogen and carbon atoms of the bicyclic framework are manifested by equivalent signals. Also, according to the 1H and 13C chemical shifts in the NMR spectra, glycolurils with electron-acceptor substituents can be clearly distinguished by the shielding of carbon atoms of C=O-groups, and with electron-donating substituents by the deshielding of CH-CH-carbons, due to the rearrangement of electron density and the occurrence of local paramagnetic contributions owing to anisotropy.

Due to high multi-functionality, bicyclic ureas of octoic type (also known as glycolurils) are used in many applications, including the manufacturing of slow-release nitrogen fertilizers, additives for paints and coatings, polymer stabilizers, psychoactive drugs, intermediates for synthesize supramolecular compounds such as cucurbiturils and bambusurils and other practically important products. Among the glycoluril derivatives, N,N,N,N-tetraacetic derivative named as tetraacetylglycoluril occupies a special place and is produced as a fine chemical and used as a bleaching activator (as an example for perborates) in detergents. Tetraacetylglycoluril as a parent compound of acylated glycolurils finds its application as a bleaching activator in detergents and successfully competes with its counterpart tetraacetylethylenediamine. The chemistry of tetraacetylglycoluril presented in the literature is fragmentary and unsystematized, and does not allow receiving a deep understanding on the chemical properties and fields of application of this available compound. We suppose that the availability and multi-functionality of the tetraacetylglycoluril makes it possible to realize its synthetic potential. In the present article the main processes to produce tetraacetylglycoluril, its chemical properties and application fields are discussed in details. Chemical properties of tetraacetylglycoluril are described in details for reactions of hydrolysis, nucleophilic substitution, N- and O-acylation of amines and alcohols. It is noteworthy that tetraacetylglycoluril can be successfully used as a soft acylating agent for biogenic organic substrates and as a building block to synthesize new supramolecular compounds.

The aim of the study was to develop composite film materials derived from modified sodium carboxymethyl cellulose and to evaluate their anti-adhesive effects. Materials and Methods. The modified film materials were obtained by dissolving sodium carboxymethyl cellulose (Na- CMC) in an aqueous solution of a modifier (glycoluril) with subsequent homogenization and drying in a vacuum drying oven at room temperature. Physicomechanical parameters of the obtained films were determined using the Instron 3369 universal electromechanical testing machine (Great Britain) equipped with a climatic chamber (300-523 K), improved video extensometer, and the MKC-25 micrometer (Russia). Cytotoxicity of glycoluril-modified film materials derived from Na-CMC was studied by incubating cell cultures of 3T3-L1 mouse fibroblasts directly with extracts from films under study using a colorimetric test. Their anti-adhesion effect was investigated on 40 female Wistar rats by modeling a flat adhesion by inducing abrasion of the cecum and suturing the deserosed surface of the abdominal wall anatomically opposite the abrasion area. The presence of adhesions was assessed on day 8 after the operation. Commercial membrane Seprafilm (USA) was used as a reference sample. Results. It was found that extracts obtained from film materials derived from Na- CMC modified with glycoluril at a concentration of 0.01 and 0.05 wt. % had no cytotoxic effect on the cell culture of mouse fibroblasts 3T3-L1. Flat adhesions were not detected when using Seprafilm. When film materials under study were placed in the abdominal cavity between the injured areas, formation of flat adhesions was not observed or observed in one case out of ten. Conclusion. The obtained films are promising for preventing adhesions as a barrier-type agent. Modifying Na-CMC with glycoluril made it possible to create films that prevent formation of flat adhesions, have improved physical and mechanical properties and no cytotoxic effect.

It is established that tetraacetylglycoluril under the action of urea, some N-substituted ureas and benzylidenebisurea in the acid-catalyzed conditions undergoes only bis-deacetylation with the formation of syn- and anti-regio-substituted N, N-diacetylglycolurils, rather than N-acetylation as it was previously shown in a similar reaction for a number of aromatic and heterocyclic amines. In the course of individual experiments, the absence of independent effect of organic solvents during boiling for several hours (alcohols, dioxane, tetrahydrofuran, dimethylsulfoxide) on the deacetylation of tetraacetylglycoluril was revealed, since in these conditions the original substrate remained unchanged. Based on the NMR spectroscopy data, by comparison the integrated intensities of methine and acetyl protons of glycoluryl fragments, we found that the bis-deacetylation of tetraacetylglycoluril in the studied conditions occurs regioselectively with an overwhelming majority of anti-N,N-diacetylglycoluril (up to 92-94%) except for benzylidenebisurea, when the content of the trans-isomer reaches 75%. A marked increase in the cis-isomer (up to 25%) of N,N-diacetylglycoluril in the case of benzylidenebisurea seems to be dictated by the specific effect on the intermediates of reaction of phenylmethylureido carbocation from eliminating urea molecule in acid-catalyzed conditions. It is shown that N, N-diacetylglycoluril in similar conditions under the action of urea and its derivatives does not undergo further deacetylation to the progenitor of bicyclic bisureas - glycoluril, primarily related to the high hydrolytic and steric resistance of these compounds. On the basis of the above research results, the reaction mechanisms of bis-deacetylation of tetraacetylglycoluril in the acid-catalyzed conditions under the action of urea and its N-methyl (phenyl) derivatives through an intermediate process of nucleophilic addition of ureas is proposed.

In the present work, the new N-methylol and O-alkyl derivatives of 4,5-dihydroxyimidazolidine-2-thione (DHIT) are synthesized. The effects of N-alkyl, N-phenyl, N-methylol, and O-alkyl substituents of DHIT on the ¹³C and ¹H signals in NMR spectra of the imidazolidine-2-thione ring are systematized using quantum chemical calculations. The shift values of carbon and hydrogen atoms are specific for the geometric isomers of the indicated DHIT derivatives. The chemical shifts of the carbon atoms of the methine groups allows for identifying the cis and trans isomers of the N-alkyl derivatives of DHIT due to the up-field shifts of the cis isomers. The introduction of an alkyl substituent at the N-position of the imidazolidine-2-thione ring leads to the up-field shifts of the carbon atoms of the ring due to the inductive effects of these groups. The ring current effect in the N-phenyl derivatives of DHIT that affects the positions of the carbon signals of the imidazolidine-2-thione ring has been found. The N-methylol derivatives of 4,5-dihydroxyimidazolidine-2-thione have been identified for the first time using 1D and 2D NMR.