Thermodynamic functions of 1-methyl-4-(methylsulfonyl)benzene solubility in nine organic solvents from T = (278.15 to 318.15) K

Highlights

• 1-Methyl-4-(methylsulfonyl)benzene solubility in nine solvents were determined.

• The solubility were correlated by using four thermodynamic models.

• The mixing properties of solutions were calculated.

Abstract

The solid-liquid equilibrium for 1-methyl-4-(methylsulfonyl)benzene in nine solvents (methanol, ethanol, acetonitrile, ethyl acetate, acetone, N,N-dimethylformamide, n-butanol, n-propanol, isopropanol) were determined at temperatures from 278.15 K to 318.15 K by using the isothermal saturation method under atmosphere pressure, and the solubility of 1-methyl-4-(methylsulfonyl)benzene in the solvents were analysed by the high-performance liquid chromatography (HPLC). On the whole, the solubility obeyed the following order from high to low for the selected solvents: N,N-dimethylformamide > acetone > acetonitrile > ethyl acetate > methanol > ethanol > n-propanol > n-butanol > isopropanol. The four thermodynamic models, modified Apelblat equation, λh equation, Wilson model and NRTL model were used to describe the solubility results obtained. The largest values of relative average deviation (RAD) and root-mean-square deviations (RMSD) were 1.48% and 56.85 × 10⁻⁴, respectively. The calculated solubility with the four models agreed well with the experimental values. Furthermore, the mixing properties, including mixing Gibbs energy, mixing enthalpy, mixing entropy, activity coefficient at infinitesimal concentration (${\gamma }_1^{\infty }$) and reduced excess enthalpy ($H_1^{\text{E,}\infty }$) were calculated for the dissolution process of 1-methyl-4-(methylsulfonyl)benzene in these solvents. The mixing process of 1-methyl-4-(methylsulfonyl)benzene was spontaneous and favourable in the selected solvents. The solubility of 1-methyl-4-(methylsulfonyl)benzene in different solvents and thermodynamic relations would be invoked as basic data and models for the purification process of 1-methyl-4-(methylsulfonyl)benzene.

Introduction

1-Methyl-4-(methylsulfonyl)benzene (CAS No. 3185-99-7), also named as 4-methylsulfonyl toluene, is an important intermediate in the synthesis of thiamphenicol [1], [2], [3], [4], [5], [6], [7], [8] and florfenicol [7], [8], which has very valuable properties of pharmacology and therapy, especially distinct anti-microbial property and are widely used as broad-spectrum antibiotics. The chemical structure of 1-methyl-4-(methylsulfonyl)benzene is shown in Fig. 1.

A substantial number of investigations has been made for production of 1-methyl-4-(methylsulfonyl)benzene [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]. At present, the main method of producing 1-methyl-4-(methylsulfonyl)benzene comprises two steps: (a) reacting p-toluensulfonylchloride and sodium bicarbonate with sodium sulfite to acquire intermediate (sodium p-tolylsulfinate), and (b) reacting the intermediate with monochloromethane in distilled water to obtain 1-methyl-4-(methylsulfonyl)benzene. The yield of 1-methyl-4-(methylsulfonyl)benzene is no greater than 85 percent. The reaction product usually contains a small amount of p-tolylsulfinate and unknown organic substance, which limits its further application in the synthesis of thiamphenicol and florfenicol. In order to obtain 1-methyl-4-(methylsulfonyl)benzene with higher purity, an effective method to purify the crude product with low cost is solvent crystallization. It is common sense that the solubility is of importance in the separation process of solids via solvent crystallization. The crystallization process of 1-methyl-4-(methylsulfonyl)benzene needs a large amount of accurate solubility data. It is unfortunate that the dependence of solubility of 1-methyl-4-(methylsulfonyl)benzene upon temperature is not available in the previous publications. Therefore, in order to determine the crystallization process and increase the purity and yield of 1-methyl-4-(methylsulfonyl)benzene, it is necessary to obtain accurate solubility values for 1-methyl-4-(methylsulfonyl)benzene in different solvents and the thermodynamic properties of solutions.

The main objectives of this work are to (1) measure the melting enthalpy of 1-methyl-4-(methylsulfonyl)benzene under atmosphere pressure; (2) determine the solubility of 1-methyl-4-(methylsulfonyl)benzene in methanol, ethanol, acetonitrile, ethyl acetate, acetone, N,N-dimethylformamide, n-butanol, n-propanol and isopropanol at temperatures ranging from (278.15 to 318.15) K by using the high-performance liquid chromatography (HPLC); (3) correlate the acquired solubility values with different thermodynamic models; and (4) calculate the mixing thermodynamic properties from the solubility for the dissolution process of 1-methyl-4-(methylsulfonyl)benzene in the nine solvents.