Dissertation:
The research of association equilibria of alkyl derivatives of urea and thiourea
mgr Monika Obrzud
Supervisor: prof. dr hab. Maria Rospenk
Abstract
The dissertation describes studies and comparison of a series of molecular mono- and disubstituted derivatives of urea and thiourea (with substituent groups from methyl to hexyl) in
solvents of increasing polarity (carbon tetrachloride, benzene, chloroform, dichloromethane and
1,2 − dichloroethane). These derivatives are characterized by a high tendency to self-associate
through the formation of intermolecular hydrogen bonds due to the presence in their structure both
groups as donors (NH) as well as proton acceptors (C=O) or (C=S). The process of association is
evidently complicated by the many varieties of structure that they can form. Such intermolecular
H − bond interactions also mean that urea-based materials have multiple applications in the area of
host–guest chemistry. Furthermore, urea derivatives play a central role in supramolecular polymer
chemistry, – as organo- , or hydro-gels, in the fiber formation of N-alkylureapeptoid oligomers. The
range of applications of urea derivatives and thiourea is very wide; the dyes to cellulose fibers in
gasoline antioxidants, corrosion inhibitors, agricultural pesticides, herbicides or as intermediates for
the synthesis of carbamates. Recently, oligoureas unique design is used as a scaffold to support the
construction of synthetic sheets and β peptide mimetics skeletons. Hydrogen bond network of
thiourea and N-alkyl derivatives play a key role in the construction of nanostructured materials,
crystal engineering and molecular recognition.
The main objective of the study was to investigate the self-association process of systems
mono- and di-alkyl derivatives of urea and thiourea in solvents of increasing polarity by using IR
spectroscopy, method of measuring the average molecular weight and the dipole moments. The
experimental data were verified by DFT quantum chemical calculations with B3PW91 correlation
functional. The key tasks are related to assess the impact of the polarity of the solvent on the
physicochemical state of aggregates. To accomplish the theoretical DFT calculations which included
the impact of the environment on the nature of interactions in the complex were carried out.
A combination of geometry optimization in polarizable continuum model (PCM) with the connection
of chloroform molecules (1,2-dichloroethane) with urea dimers enabled to obtain the expected
theoretical simulation compliance with the experiment. Adoption such combined technique of
calculation was based on the assumption that during the formation of dynamic equilibrium
in solution a competitive processes of non-conventional hydrogen bonds C-H.. O=C(C=S) formation
and the classical interactions N-H...O=C(C=S) take place. It has been proved that the molecules of
the solvent can easily form a complex with a basic active center of alkylurea (thiourea), blocking the
protonacceptor centers and reducing the self-association process of examined urea and thiourea
derivatives. The results of the research are self-association models developed for alkyl derivatives of
urea and their thioanalogs with regard to the size, form, type, and number of substituents.
Association constants were determined (Kas). At 40°C, the equilibrium constant was calculated on
the basis of data obtained in two independent methods of measurement: IR spectroscopy and
measurements of mean molecular weights. Good agreement of experimental data of both research
techniques were found up to concentration of 0.03mol/dm3. For higher concentrations the monomer
concentration estimated on the basis of low intense absorption bands of NH was erroneous.
Limitations occurring in the IR spectra, in this range of concentrations were overcome by using of
more accurate osmometric measurements. Development of a mathematical model based on the
combination of the results of both methods has allowed a more accurate determination of equilibrium
constants. Association rates at 25°C were determined from measurements of IR spectra. The type of
associates have been assessed following the dipole moments measured as a function of
concentration, and on the results of density-functional theory (DFT) calculations on the structure and
energy of particular species. All of the urea derivatives demonstrated an increase in dipole moment
with increased concentration, resulting in stronger NH2…O hydrogen bond interactions and leading to
linear-type aggregation. Contrastingly, the dipole moments of the N,N’− dimethylthiourea and
mono-N-alkyl-substituted thioureas decreased with concentration and suggest that cyclic dimers or
trimers are formed by C=S…(HR)2N-C=S interactions. The mechanisms of self-aggregation
in different polar solvents were followed using IR spectroscopy, with two gradual aggregation
constants determined. It was demonstrated that a minimum of two equilibrium constants are
necessary to describe the association processes of dialkylureas and thioureas. The first constant, K1,
describes dimer formation and a second constant, K2, describes subsequent multimer formation. The
N,N’− symmetric derivatives of urea exhibited strong association in nonpolar solvents (C6H6, CCl4),
while lower but important association was found in the more “active” solvents CHCl3 and C2H4Cl2.
In N,N’− thioureas aggregation is similar to those of their urea counterparts, with the exception of
the extent of association. In polar solvents mono-derivatives aggregate more effectively than the
disubstituted compounds where the bulkier aliphatic chains prevent H-bonding. Density-functional
theory calculation of these processes showed that reliable and better results could be obtained if
solvent interactions were considered, with a specific combination of local and bulk effects.
Differences between urea and thiourea derivatives result from the fact that the ureas are stronger
bases and, therefore, more active in aggregation. Model calculations also show that interaction angles
involving electron lone pairs are narrower in the urea derivatives, which thus favors linear
aggregation. Branched aggregation is observed for the thioureas. It was shown that a decrease in
alkyl chain length may lead to growth in aggregation because of steric hindrance of the H-bonded
interactions of the longer chains.