FACTORS AFFECTING THE FORMATION REACTION OF HEXAMETHYLENE BIS-[(ALKYL)-CARBAMATES] DERIVATIVES

ABSTRACT

This article aims to elucidate the factors affecting the reaction of hexamethylene bis-[(alkyl)-carbamates] derivatives, with a particular focus on the influence of time, primary, secondary and tertiary alcohols on the reaction progress at a temperature (25-30°C) conducive to the reaction medium. Additionally, the article explores the reasons for the high mobility of the "OH" group and the loss of hydrogen bonds and internal and intermolecular bonds. Additionally, it was determined that the formation of bis-carbamates among DMFA, pyridine, acetonitrile, TGF, dioxane, and heptane solvents is highly efficient in solvents mineralising in the reaction medium and in isocyanate groups with high nucleophilicity in the OH group and electrophilicity in carbon atoms.

АННОТАЦИЯ

В данной статье с целью обеспечения высокого выхода производных гексаметилен-бис-[(алкил)-карбаматов] рассмотрены факторы, влияющие на реакцию: влияние времени, первичных, вторичных и третичных спиртов на ход реакции, при температуре (25-30⁰С), благоприятная для реакционной среды. Изучены причины высокой подвижности группы «ОН» и потери водородных связей, внутренних и межмолекулярных связей. Также установлено, что образование бис-карбаматов среди растворителей ДМФА>пиридин>ацетонитрил>ТГФ>диоксан>гептан высокоэффективно в растворителях, минерализующихся в реакционной среде, и в изоцианатных группах с высокой нуклеофильностью по ОН-группе и электрофильностью по углероду атомы.

Keywords: carbamate, bis-carbamate, isocyanate, GMDI, primary, secondary, tertiary alcohols, pyridine, acetonitrile, TGF, dioxane

Ключевые слова: карбамат, бис-карбамат, изоцианат, ГМДИ, первичные, вторичные, третичные спирты, пиридин, ацетонитрил, ТФР, диоксан

Introduction

At the present time, carbamate and bis-carbamate derivatives are substances that possess a variety of biological and pharmacological activities. These substances are employed in a number of technological applications, including rubber vulcanisation, as accelerators, in the production of lubricants, and in the production of polymers. Additionally, they are utilised as corrosion inhibitors. Additionally, they are of significant value in agricultural applications as pesticides, herbicides, fungicides, insecticides, nematocides, acaricides, bactericides, and growth accelerators.

Mono- and diisocyanates are highly reactive substances that are employed in the synthesis of a diverse array of compounds, many of which possess significant theoretical and practical interest. The significance of isocyanates is further amplified in the synthesis of urea derivatives, which are formed through the reaction of isocyanates with alcohols [1]. In examining the chemical properties of isocyanates, it is essential to concentrate on the structure of the -N=C=O groups and the distribution of electron clouds in isocyanate molecules, both in their static and dynamic forms. These factors frequently serve as the determining factors in the nature of the reactions in which isocyanates are involved.

Experimental part

The time-dependent behaviour of hexamethylene bis- [(alkyl)-carbamates] was investigated. In order to develop an understanding of the bis-carbamate synthesis and technology, and to identify optimal conditions, we conducted a study to examine the effects of reaction progress, time, temperature, and solvent nature on the resulting product [2]. The reaction was studied with GMDI in a thermostat at temperatures between 25 and 30°C in order to ensure the high yield of derivatives of hexamethylene bis-[(alkyl)-carbamates], as well as to determine the influence of reaction time. The results of the test are presented in graphical form in Figure 1.

Figure 1. A time versus time plot of hexamethylene bis-[(alkyl)-carbamates]

The yield of hexamethylene bis-[(alkyl)-carbamates] in various reactions with alcohols is arranged in the following series:

As illustrated in Figure 1, the yield of bis-carbamates in the reaction with low radicals of alcohols with a normal structural configuration is markedly diminished in alcohols with isostructural and extended radical structures. This phenomenon can be attributed to an increase in the number of oxygen atoms or the density of the alcohols in question. The nucleophilic attack is weakened from the end of the chain when reacting with alcohols with a secondary, tertiary isostructure and a long radical structure of GMDI. This is due to an increase in steric factors and a decrease in oxygen atom or density [3].

Method and Discussion section

The objective of this study is to examine the temperature dependence of the reaction. The technology employed in the synthesis of hexamethylene bis-[(alkyl)-carbamates] and the selection of an appropriate temperature for the reaction medium are of significant importance in the successful completion of such reactions. In the process of obtaining derivatives of hexamethylene bis-[(alkyl)-carbamates], if the reaction mass consisting of alcohol, GMDI, DMFA, and triethylamine is cooled to 0°C, the yield of the product is 10-11%. As the temperature rises, the yield of the product increases, reaching 40% at 15°C and 50-70% at 20°C. An increase in temperature to 25-30°C results in a yield of bis-carbamate derivatives of 75-100%. Figure 2 illustrates the yield of hexamethylene bis-[(alkyl)-carbamates].

Figure 2. Temperature dependence plot of hexamethylene bis-[(alkyl)-carbamates]

The elevated yield observed at temperatures between 25 and 30°C can be attributed to the enhanced mobility of the -OH group at these temperatures. This phenomenon can be rationalised by the disruption of hydrogen bonding, intramolecular and intermolecular bonds. This results in the determined quantity of solvent binding to the -N=C=O group, thereby activating it. The free hydroxyl group is involved in the synthesis of further bis-carbamates.

This study examines the influence of solvent nature on the yield of bis-carbamates. In order to obtain a high yield of bis-carbamates and their derivatives, as well as to determine the nature of the solvent, a series of experiments were conducted using DMFA in a range of electron donor solvents, including pyridine, dioxane, acetonitrile and heptane. The objective is to guarantee the ionisation of the participating substances and to intensify the reaction. The release of hexamethylene bis-[(alkyl)-carbamates] is dependent on the nature of the solvent. The order of preference for the most effective solvent is as follows: DMFA>pyridine > acetonitrile > TGF > dioxane > heptane.

The initial substances remained unaltered throughout the course of the reaction in heptane. The highest yields of bis-carbamates were observed in the presence of DMFA and pyridine, which can be attributed to the higher basicity of these reagents. The order of decrease is as follows: The order of reactivity was found to be DMFA > pyridine > acetonitrile > TGF > dioxane > heptane (Figure 3).

Figure 3. Solvent nature plot of hexamethylene bis-[(alkyl)-carbamates]

The elevated yield of bis-[(alkyl)-carbamates] and their derivatives in DMFA throughout the reaction can be attributed to the solvent's polarity, acidic nature, proton-releasing properties, solubility in diisocyanate, and capacity to dissolve and mineralise the reaction product. This results in an increase in the basicity of the bases and the strength of the nucleophile [4].

Furthermore, pyridine exhibits excellent solubility properties. The unshared electron pair on the nitrogen atom represents the basicity of pyridine, which is situated in a flat trigonal orbital, thereby enabling π-donor-acceptor bonding. Pyridines exhibit a high degree of carbonylation ability, and the phenomenon of nucleophilic coupling is evident in the A_N reaction. The solvents acetonitrile, TGF and dioxane belong to the group of dipolar, deprotonated solvents, and also have a high dielectric constant (E>15) and a large dipole moment (μ>2.5). These solvents are classified as π-donors and are capable of performing specific mineralisation of the reaction mixture in a basic environment. Due to their high polarity, they are fully efficient in the AN nucleophilic coupling reaction and can be easily mineralised with diisocyanates and alcohols. Following an examination of the impact of solvent nature, the following conclusion was reached. The formation of bis-carbamates is highly efficient in solvents that undergo mineralisation in the reaction medium and in isocyanate groups with high nucleophilicity in the "OH" group and high electrophilicity of carbon atoms.

As presented in the global literature, N-arylthiocarbamates with the formula X_nC₆H_4-nNHCOSR (R=CH₃, C₂H₅, cycloalkyl, X-halogen, U-alkyl) were prepared by researchers in the form of X_nC₆H_4nN=C=O with R-SH in inert solvents. The yield obtained through the reaction in the presence of tertiary amines at temperatures ranging from -30 to 150°C was found to be 64% [5].

The reaction of PhCONCO with НСºС-СН₂ОН  gives Ph-С(О)-NН-С(О)-О-СН₂-СºСН in an 86% yield. The reaction of СН₃СН₂-О-СºС-С₂Н₅  CI-SO₂N=C=O with CI-SO₂N=C=O is conducted in CCI₄ at temperatures of -20°C, -40°C, and -60°C, followed by heating and evaporation. The resulting product, 50-75% 2,2-dioxane-4, ethoxy-5-ethyl-6-chloro-2,2,3-oxothiazine, is obtained. The aforementioned method yields 2,2-dioxy-4-ethoxy-5-methyl-6-chloro-1 from С₂Н₅-О-С≡С-С₂Н₅ F-SO₂-N=C=O and Ph-C(O)-NCO 2,3-oxathiazine. The process was conducted using N,N¹-dibutylurea, wherein the urea underwent reamination.

The method is described in the patent literature, but the conditions of the process, methods of separation of reaction products and thermodynamic effects are not provided. The conditions of reamination in two stages, namely in solvents and in urea liquids, have also been the subject of study. Consequently, an investigation was conducted into the temperature limitations of the reaction. It has been demonstrated that the optimal resupply temperature falls within the range of 140-160°C. The German scientists conducted the reaction of the formula C₂H₅O-C  C-C₂H₅ with Cl-SO₂N=C=O in CCl₄, pentane, and CH₂CI₂ at temperatures ranging from -20 to -40 to -60 degrees Celsius. The solution is heated to 20°C and evaporated, resulting in the formation of 2,2-dioxy-4-ethoxy-5-C₂H₅-6-chloro-1,2,3-oxatriazine in a yield of 50-75%. Attempts to obtain azetinone from RhCONCO and various acetylenes were unsuccessful. The data obtained from the -IR spectra are presented.

Conclusions

Based on our research, the most favorable temperature for the synthesis of bis-[(alkyl)-carbamates] derivatives was determined to be -25-30⁰С, the catalyst triethylamine (or pyridine), the solvent DMFA, and the reaction time was 3-4 hours.

References:

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3. Orlova, A. A., & Mantrov, S. N. (2024). Obtaining N-butyl-O-alkyl carbamates by alcoholism of symmetrical dibutyl urea. The Chemistry and Technology of Synthetic Biologically Active Substances: Moscow: Publishing House of the D.I. Mendeleyev University of Chemical Technology of Russia. 2005, pp. 96–97.
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