Design, Synthesis, and Spectral Properties of Novel 2-Mercaptobenzothiazole Derivatives

This paper is focused on the optimalization of methods for the synthesis, isolation, and purification of 2-mercaptobenzothiazole-based acrylic and methacrylic monomers. The structures of the newly synthesized compounds were confirmed through infrared (IR) and nuclear magnetic resonance spectroscopy (NMR). Spectroscopic properties of the resulting 2-mercaptobenzothiazole derivatives were determined based on their absorption spectra and molar absorption coefficients in solvents with varying polarities. A correlation was established between the calculated density functional theory (DFT) energies and Frontier Molecular Orbitals and the experimental observations, confirming their consistency. The practical utility of the synthesized compounds, particularly in future polymerization processes, hinges on a thorough understanding of these properties.


Introduction
The 2-mercaptobenzothiazoles (MBT) (Figure 1) constitute a significant group of bioactive and industrially crucial organic compounds.It is noteworthy that their derivatives are of huge interest in scientific research owing to their potential pharmacological properties [1].The widespread use of these substances in the medical field, such as their application as anti-inflammatory [2], antibacterial [3,4], and antifungal agents [5], along with their efficacy in treating diseases such as cancer and cardiovascular illnesses [6], has garnered considerable attention.The interest in this group of compounds arises not only from their medicinal applications but also from their diverse uses in various industries: 2-mercaptobenzothiazole serves as a widely utilized organic corrosion inhibitor [7] for copper [8,9] and zinc [10,11], and as a component of self-healing and anticorrosion smart coatings [12][13][14][15].Larsson et al. [16] suggested that MBT can serve as an additive in dye solar devices.Moreover, 2-mercaptobenzothiazole and its derivative zinc 2-mercaptobenzothiazole (ZMBT) [17] are commonly used as 'hemi-ultra' accelerators in the vulcanization process of both natural and synthetic rubber.Additionally, they find applications as plasticizers in the rubber industry [18][19][20].Heteroaromatic thiols, including MBT, among others, have been utilized as co-initiators for type II photo-initiators composed of camphoroquinone and isopropylthioxanthone.Kinetic data indicate their efficiency as coinitiators, comparable to aromatic amines.Due to their ability to readily donate hydrogen atoms, some of these thiols have been employed as co-initiators of hexaarylbisimidazoles (HABI) [21].In other study, Degirmenci et al. copolymerized a methacrylic monomer containing a benzothiazole disulfide group with a hydrophilic polyethylene glycol (PEG)based monomer, resulting in a redox-responsive functional polymer.The straightforward synthesis of these copolymers, which are highly functionalizable, and their application in the preparation of reversibly functionalizable coatings, establishes a versatile interface for a range of biomedical applications [22].Acrylic acid derivatives, commonly referred to as acrylates, encompass salts and esters derived from acrylic and methacrylic acid.Characterized by a vinyl group linked to a carboxyl group, these compounds undergo facile polymerization owing to an active double bond within their structure.As monomers, they rank among the most widely employed in the synthesis of polymeric plastics.The inherent compatibility of acrylic and methacrylic monomers facilitates polymerization not only with each other but also with diverse monomers, thereby contributing to the fabrication of numerous polymer compositions [23,24].Manipulating the composition and proportions allows for the production of materials with varied final properties [25].Acrylic polymers, renowned for their diverse properties, encompassing excellent durability, transparency, strength, UV stability, ease of dyeing, and color fastness, find extensive utility in the production of various commodities.These polymers play pivotal roles in optics [26] and medicine [27,28] and numerous industries, notably in the manufacturing of paints and adhesives [29], for the design of macromolecular self-organizing materials [30,31], as well as applications in the textile industry.Their versatility extends across a spectrum of forms, ranging from very soft adhesive materials to loose powders, and even to rigid, hard boards and consumer products.
The distinctive characteristics of 2-mercaptobenzothiazole and its acrylic and methacrylic acid derivatives motivated the development of a novel group of compounds (Figure 2).These newly synthesized compounds can be regarded as functional monomers, showing potential applications in the expansive domains of polymer chemistry and technology.The objectives of this paper is the synthesis and study on the structures and spectroscopic properties of the new compounds based on 2-mercaptobenzothiazole.It is assumed that the indicated acrylate and methacrylate derivatives of 2-mercaptobenzothiazole have the potential to serve as photo-initiators of radical polymerization of various acrylate monomers.Furthermore, some of these compounds can be used as photo-initiators, as well as serve as attractive building units and components for advanced polymeric materials with a high refractive index.Examples of such applications include their use in foldable intraocular lenses [32] and for industrial applications, such as coatings [33,34].Acrylic acid derivatives, commonly referred to as acrylates, encompass salts and esters derived from acrylic and methacrylic acid.Characterized by a vinyl group linked to a carboxyl group, these compounds undergo facile polymerization owing to an active double bond within their structure.As monomers, they rank among the most widely employed in the synthesis of polymeric plastics.The inherent compatibility of acrylic and methacrylic monomers facilitates polymerization not only with each other but also with diverse monomers, thereby contributing to the fabrication of numerous polymer compositions [23,24].Manipulating the composition and proportions allows for the production of materials with varied final properties [25].Acrylic polymers, renowned for their diverse properties, encompassing excellent durability, transparency, strength, UV stability, ease of dyeing, and color fastness, find extensive utility in the production of various commodities.These polymers play pivotal roles in optics [26] and medicine [27,28] and numerous industries, notably in the manufacturing of paints and adhesives [29], for the design of macromolecular self-organizing materials [30,31], as well as applications in the textile industry.Their versatility extends across a spectrum of forms, ranging from very soft adhesive materials to loose powders, and even to rigid, hard boards and consumer products.
The distinctive characteristics of 2-mercaptobenzothiazole and its acrylic and methacrylic acid derivatives motivated the development of a novel group of compounds (Figure 2).These newly synthesized compounds can be regarded as functional monomers, showing potential applications in the expansive domains of polymer chemistry and technology.The objectives of this paper is the synthesis and study on the structures and spectroscopic properties of the new compounds based on 2-mercaptobenzothiazole.It is assumed that the indicated acrylate and methacrylate derivatives of 2-mercaptobenzothiazole have the potential to serve as photo-initiators of radical polymerization of various acrylate monomers.Furthermore, some of these compounds can be used as photo-initiators, as well as serve as attractive building units and components for advanced polymeric materials with a high refractive index.Examples of such applications include their use in foldable intraocular lenses [32] and for industrial applications, such as coatings [33,34].

Materials
All the reagents and solvents were purchased from Sigma-Aldrich (Poznań, Poland) and utilized without additional purification.The spectroscopic studies necessitated the use of chemicals with the highest purity (≥99%).

Synthesis
The synthesis followed the methodology outlined in [33].The method of purification was modified.Substituted 2-mercaptobenzothiazole (28 mmol) and sodium bicarbonate (28.5 mmol, 2.4 g) were dissolved in 10 mL of dimethylformamide at 60 °C.Then, 2-chloroethyl acrylate (29 mmol, 3.47 mL) or 2-chloroethyl methacrylate (29 mmol, 2.93 mL) was added, dropwise.The reaction mixture was refluxed overnight, washed with a 5% NaOH aqueous solution, and extracted with diethyl ether.The organic layer was separated and dried using MgSO4, filtered, and the solvent was removed under vacuum.The crude oil underwent purification through silica gel column chromatography using dichloromethane as the eluent, with fractions collected at 285 nm.

Materials
All the reagents and solvents were purchased from Sigma-Aldrich (Pozna ń, Poland) and utilized without additional purification.The spectroscopic studies necessitated the use of chemicals with the highest purity (≥99%).

Synthesis
The synthesis followed the methodology outlined in [33].The method of purification was modified.Substituted 2-mercaptobenzothiazole (28 mmol) and sodium bicarbonate (28.5 mmol, 2.4 g) were dissolved in 10 mL of dimethylformamide at 60 • C.Then, 2-chloroethyl acrylate (29 mmol, 3.47 mL) or 2-chloroethyl methacrylate (29 mmol, 2.93 mL) was added, dropwise.The reaction mixture was refluxed overnight, washed with a 5% NaOH aqueous solution, and extracted with diethyl ether.The organic layer was separated and dried using MgSO 4 , filtered, and the solvent was removed under vacuum.The crude oil underwent purification through silica gel column chromatography using dichloromethane as the eluent, with fractions collected at 285 nm.

Experimental Measurements 2.3.1. NMR Measurements
The 1 H and 13 C NMR spectra were measured on a Bruker Ascend III spectrometer operating at 400 MHz (Bydgoszcz, Poland).Chloroform served as the solvent, and tetramethylsilane (TMS) was used as the internal standard.Chemical shifts (δ) are reported in ppm relative to TMS and coupling constants (J) are expressed in Hz.

UV-Vis Measurements
The absorption spectra were measured at room temperature in a quartz cuvette (1 cm) using an Agilent Technology UV-Vis Cary 60 Spectrophotometer (Bydgoszcz, Poland).

FT-IR Measurements
Infrared spectra were measured using an Alpha Bruker's compact FT-IR spectrometer equipped with diamond ATR, covering the range of 4000-360 cm −1 (Bydgoszcz, Poland).

Boiling Point
The boiling point was measured on the Melting Point M-565 Apparatus (Buchi; Bydgoszcz, Poland) with the following parameters: temperature gradient 5.0 • C/min, barometric pressure 1013 mbar, and boiling frequency 0.6 Hz.
The injector port was held at 270 • C and used in the split mode (5:1), and 1 µL injections were made.The temperature program used for the analysis was as follows: 80 • C (2 min), ramped at 15 • C/min to 250 • C, and held for 15 min.Helium was used as the carrier gas at a flow rate of 1 mL min −1 .
Full-scan mass spectra were recorded with an m/z range of 50-400 in electron-impact mode at 70 eV.
The transfer line and ion source temperatures were set at 280 and 230 • C, respectively.The scan rate was 2.9 scan/s, with a cathode delay time of 5 min.The SCAN mode was used for identification of analytes.

Boiling Point
The boiling point was measured on the Melting Point M-565 Apparatus (Buchi; Bydgoszcz, Poland) with the following parameters: temperature gradient 5.0 °C/min, barometric pressure 1013 mbar, and boiling frequency 0.6 Hz.
The injector port was held at 270 °C and used in the split mode (5:1), and 1 µL injections were made.The temperature program used for the analysis was as follows: 80 °C (2 min), ramped at 15 °C/min to 250 °C, and held for 15 min.Helium was used as the carrier gas at a flow rate of 1 mL min −1 .
Full-scan mass spectra were recorded with an m/z range of 50-400 in electron-impact mode at 70 eV.
The transfer line and ion source temperatures were set at 280 and 230 °C, respectively.The scan rate was 2.9 scan/s, with a cathode delay time of 5 min.The SCAN mode was used for identification of analytes.
The final products were separated and obtained in the form of oils, and were then purified via flash chromatography using dichloromethane as the eluent.
The structures and purity of the obtained compounds were confirmed through nuclear magnetic resonance spectra, including 1 H and 13 C isotopes, as well as 1 H- 13 C HMQC and 1 H- 13 C HMBC spectra.The most characteristic chemical shifts for 1 H and 13 C NMR are collected in Tables 1 and 2, respectively.The 1 H-NMR signals for =CH 2 in acrylic 2-mercaptobenzothiazole derivatives (1-3) appeared as doublets at δ = 5.75-6.41ppm in CDCl 3 .The same protons in methacrylate derivatives (4-6) exhibited signals at δ = 5.47-6.13ppm in CDCl 3 , appearing as a singlet (Figure 3).An adjacent hydrogen atom bonded to a carbon involved in the formation of a carbon-carbon double bond appeared at approximately 6 ppm as a quartet.Alkyl protons from CH 2 groups were observed at around 4.5 ppm and 3.5 ppm for CH 2 -O and CH 2 -S, respectively.They were present as triplets in both cases.Hydrogen atoms bonded to the aromatic ring were observed in the characteristic range for aromatic protons from 7 to 8 ppm.These chemical shift values and signal patterns align with those previously reported by us for related compounds [42].Chemical shift values were computed to validate the experimental data.Both 1 H and 13 C NMR chemical shift values fell within the calculated range.The deviations observed were attributed to the common use of dimethyl sulfoxide instead of chloroform during calculations, demonstrating the impact of changing the solvent on chemical shift values.In the 13 C NMR spectra, the most downfield peak corresponds to the carbonyl carbon atom C=O, resonating at approximately 165 ppm for acrylic (1-3) and approximately 167 ppm for methacrylic 2-mercaptobenzothiazole derivatives (4-6).On the most shielded part of the spectrum, the chemical shifts of carbons in alkane groups were observed.The chemical shifts of CH 2 -O and CH 2 -S resonated at around 63 ppm and 32 ppm, respectively (Supplementary Materials).Consistent with the 1 H NMR spectra, these chemical shift values for all carbon atoms align with those previously described for related compounds [42].
Chemical shift values were computed to validate the experimental data.Both 1 H and 13 C NMR chemical shift values fell within the calculated range.The deviations observed were attributed to the common use of dimethyl sulfoxide instead of chloroform during calculations, demonstrating the impact of changing the solvent on chemical shift values.

Vibrational Analysis
In the identification of new chemical compounds, infrared (IR) spectroscopy serves as one of several tools.When combined with techniques such as nuclear magnetic resonance (NMR) spectroscopy, IR spectroscopy enhances the comprehensive understanding of the properties of a compound.For the study of the title compounds, vibrational spectroscopy and quantum chemical calculations using the B3LYP functional and 6-311+G(d,p) basis set were employed.Sharp bands of strong intensity, observed at 1714-1721 cm −1 (calculated values: 1769-1795 cm −1 ), in the analyzed of spectra of compounds were attributed to stretching vibrations of the C=O group.Additionally, in the range of 1632-1636 cm −1 (calculated values: 1653-1689 cm −1 ), the characteristic band of (C=C) vibrations of alkene fragments was observed.The most characteristic vibrational bands are summarized in Table 3.

Vibrational Analysis
In the identification of new chemical compounds, infrared (IR) spectroscopy serves as one of several tools.When combined with techniques such as nuclear magnetic resonance (NMR) spectroscopy, IR spectroscopy enhances the comprehensive understanding of the properties of a compound.For the study of the title compounds, vibrational spectroscopy and quantum chemical calculations using the B3LYP functional and 6-311+G(d,p) basis set were employed.Sharp bands of strong intensity, observed at 1714-1721 cm −1 (calculated values: 1769-1795 cm −1 ), in the analyzed of spectra of compounds were attributed to stretching vibrations of the C=O group.Additionally, in the range of 1632-1636 cm −1 (calculated values: 1653-1689 cm −1 ), the characteristic band of (C=C) vibrations of alkene fragments was observed.The most characteristic vibrational bands are summarized in Table 3.

Vibrational Analysis
In the identification of new chemical compounds, infrared (IR) spectroscopy serves as one of several tools.When combined with techniques such as nuclear magnetic resonance (NMR) spectroscopy, IR spectroscopy enhances the comprehensive understanding of the properties of a compound.For the study of the title compounds, vibrational spectroscopy and quantum chemical calculations using the B3LYP functional and 6-311+G(d,p) basis set were employed.Sharp bands of strong intensity, observed at 1714-1721 cm −1 (calculated values: 1769-1795 cm −1 ), in the analyzed of spectra of compounds were attributed to stretching vibrations of the C=O group.Additionally, in the range of 1632-1636 cm −1 (calculated values: 1653-1689 cm −1 ), the characteristic band of (C=C) vibrations of alkene fragments was observed.The most characteristic vibrational bands are summarized in Table 3.

Vibrational Analysis
In the identification of new chemical compounds, infrared (IR) spectroscopy serves as one of several tools.When combined with techniques such as nuclear magnetic resonance (NMR) spectroscopy, IR spectroscopy enhances the comprehensive understanding of the properties of a compound.For the study of the title compounds, vibrational spectroscopy and quantum chemical calculations using the B3LYP functional and 6-311+G(d,p) basis set were employed.Sharp bands of strong intensity, observed at 1714-1721 cm −1 (calculated values: 1769-1795 cm −1 ), in the analyzed of spectra of compounds were attributed to stretching vibrations of the C=O group.Additionally, in the range of 1632-1636 cm −1 (calculated values: 1653-1689 cm −1 ), the characteristic band of (C=C) vibrations of alkene fragments was observed.The most characteristic vibrational bands are summarized in Table 3.

Spectroscopic Studies
The compounds under study, akin to those previously examined [42], exhibited distinct absorption in the wavelength range from 260 to 350 nm.Solvent polarity showed a weak impact on the position of maximum absorption.However, a slight shift toward a lower wavelength was noticeable when methanol was used (Figure 4A).The transition from acrylic (compounds 1-3) to methacrylic (compounds 4-6) did not significantly affect the position of the absorption band (Figure 4B), which was primarily influenced by the type and position of the substituent attached to the phenyl group.In general, the shape of the absorption spectrum and the position of its maximum do not depend on the type of substituent, but on its place.The presence of chlorine at locant six on the benzene ring of 2-mercaptobenzothiazole (compound 2 and 5) resulted in slight shifts toward higher wavelengths (bathochromic shift) compared to the compound with the same substituent at position five (3 and 6) (Figure 4C).The molar absorption coefficient (ε) in the 1−6 series varied between 8800 and 16,200 M −1 •cm −1 (Table 4).The spectroscopic characteristics of the compounds studied are presented in Table 4.

Spectroscopic Studies
The compounds under study, akin to those previously examined [42], exhibited distinct absorption in the wavelength range from 260 to 350 nm.Solvent polarity showed a weak impact on the position of maximum absorption.However, a slight shift toward a lower wavelength was noticeable when methanol was used (Figure 4A).The transition from acrylic (compounds 1-3) to methacrylic (compounds 4-6) did not significantly affect the position of the absorption band (Figure 4B), which was primarily influenced by the type and position of the substituent attached to the phenyl group.In general, the shape of the absorption spectrum and the position of its maximum do not depend on the type of substituent, but on its place.The presence of chlorine at locant six on the benzene ring of 2-mercaptobenzothiazole (compound 2 and 5) resulted in slight shifts toward higher wavelengths (bathochromic shift) compared to the compound with the same substituent at position five (3 and 6) (Figure 4C).The molar absorption coefficient (ε) in the 1−6 series varied between 8800 and 16,200 M −1 •cm −1 (Table 4).The spectroscopic characteristics of the compounds studied are presented in Table 4.

Computational Details
The HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital) values provide insights into the energy levels of molecular orbitals within a given molecule.This information is crucial for comprehending the chemical properties of molecules, reactivity, and behavior in chemical reactions.Similar to the previously tested compounds [42], the calculations indicated that the derivatives with electron-donating groups exhibited the highest reactivity (compounds 1 and 4).Such molecules showed the lowest values of hardness and energy gaps (Table 5).Additionally, the higher energy gap values of 2-(2-benzothiazolylthio)ethyl methacrylate derivatives (4-6) suggest that they may be less reactive than their acrylic counterparts (1-3) (Figure 5).Notably, there was no evident impact of solvent polarity on the calculated parameters.viously tested compounds [42], the calculations indicated that the derivatives with electron-donating groups exhibited the highest reactivity (compounds 1 and 4).Such molecules showed the lowest values of hardness and energy gaps (Table 5).Additionally, the higher energy gap values of 2-(2-benzothiazolylthio)ethyl methacrylate derivatives (4-6) suggest that they may be less reactive than their acrylic counterparts (1-3) (Figure 5).Notably, there was no evident impact of solvent polarity on the calculated parameters.The activity of the photoinitiation of free-radical photopolymerization of the studied compounds will be confirmed by kinetic studies in a future paper.The activity of the photoinitiation of free-radical photopolymerization of studied compounds will be confirmed by kinetic studies in a future paper.

Conclusions
The synthesis of novel 2-(2-benzothiazolylthio)ethyl acrylates (1-3) and methacrylates (4-6) is described here.The chemical structures of the synthesized compounds were confirmed by using various spectroscopic methods.Experimental spectroscopic data were effectively reproduced and complemented by quantum chemical DFT theoretical calculations.The study revealed that the replacement of the hydrogen atom in acrylate derivatives (R 3 = H in Scheme 1) on the methyl group to methacrylate (R 3 = CH 3 in Scheme 1) had only a minor effect on their spectroscopic properties.In addition, it was shown that the solvent had a weak impact on the position of the absorption band, while the structure of the compound and the type and position of the substituent significantly influenced it.The substitution of the same substituent into the C6 (R 2 in Scheme 1) position of the phenyl ring of the 2-mercaptobenzothiazole resulted in a slight shift toward a higher wavelength (bathochromic shift) when compared to the compound with substitution into the C5 (R 1 in Scheme 1) position.The obtained HOMO and LUMO energy values indicated that 2-(2-benzothiazolylthio)ethyl acrylate derivatives (1-3) exhibited greater reactivity compared to 2-(2-benzothiazolylthio)ethyl methacrylate derivatives (4)(5)(6).Further investigations will be focused on studying the activity of new 2-mercaptobenzothiazolebased acrylates and methacrylates in photo-initiating systems for radical polymerization of acrylates.

Table 3 .
Characteristic band strength values of the synthesized compounds.

Table 3 .
Characteristic band strength values of the synthesized compounds.

Table 3 .
Characteristic band strength values of the synthesized compounds.

Table 3 .
Characteristic band strength values of the synthesized compounds.

Table 5 .
The values of hardness (η), energy gap, and energies of HOMO and LUMO orbitals estimated for all compounds.

Table 5 .
The values of hardness (η), energy gap, and energies of HOMO and LUMO orbitals estimated for all compounds.