Solid−liquid phase equilibrium and mixing properties of 2-Cyano-4′-methylbiphenyl in pure solvents

https://doi.org/10.1016/j.jct.2016.07.050Get rights and content

Highlights

  • Solubility of 2-Cyano-4′-methylbiphenyl in eight pure solvents were determined by using UV spectrometer method.

  • The experimental solubility data of 2-Cyano-4′-methylbiphenyl were correlated and analyzed by three thermodynamic models.

  • Mixing thermodynamic properties of 2-Cyano-4′-methylbiphenyl were calculated and discussed.

Abstract

Solid–liquid equilibrium data of 2-Cyano-4′-methylbiphenyl (OTBN) are essential for the design and optimization of its production process. In this work, the solubility data of OTBN in pure solvents including 2-propanol, (R)-(−)-2-butanol (2-butanol, for short), methyl acetate, ethyl acetate, propyl acetate, butyl acetate, acetone and acetonitrile were determined in different temperature ranges from (268.05 to 303.25) K by using UV spectrometer method under atmospheric pressure. It was found that the order of OTBN solubility in these selected pure solvents at given temperature is acetone > methyl acetate > ethyl acetate > propyl acetate > butyl acetate > 2-butanol > 2-propanol and methyl acetate > acetonitrile > 2-butanol. In the temperature range investigated, the solubility data of OTBN increase with the increasing of temperature in all eight solvents. Furthermore, the modified Apelblat equation, the Wilson model and the NRTL model were applied to correlate the experimental solubility data. The correlated results are consistent with the experimental results. Finally, the mixing thermodynamic properties of OTBN in different solvents were calculated and analyzed based on the experimental solubility data and the Wilson model.

Introduction

2-Cyano-4′-methylbiphenyl (OTBN, C14H11N, molecular weight: 193.248 g·mol−1, CAS Registry No. 114772-53-1, shown in Fig. 1) is widely used as an important synthetic intermediate for the production of various sartans, such as losartan, irbesartan, valsartan and telmisartan [1], [2], [3], [4], [5]. As one of the most important selective angiotensin II receptor antagonist, the sartans are extensively employed in the treatment of cardiovascular diseases owing to its characteristics of high receptor-selectivity, good tolerance and long-lasting [6].

In pharmaceutical industry, high-purity OTBN is essential for the producing of high quality sartans. During the preparation process of OTBN, crude OTBN is prepared by concentrating and filtrating and then is purified by crystallization method. Solution crystallization process is one of the key steps that will influence the purity, yield, crystal size and crystal habit of OTBN. In order to design and optimize the crystallization process of OTBN, information about solid–liquid equilibrium of solid OTBN in different solvents are necessary.

However, up to date, the accurate solubility data of OTBN have not been reported in literature and there is little information about the temperature dependence of the solubility of OTBN. In this study, the solubility data of OTBN in pure solvents including 2-propanol, 2-butanol, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, acetone and acetonitrile were determined by using UV spectrometer method. To extend the applicability of the solubility data, the modified Apelblat equation, the Wilson model and the NRTL model were used to correlate the experimental solubility data of OTBN. Furthermore, the mixing thermodynamic properties of OTBN in different solvents were calculated and analyzed based on the experimental solubility data and the Wilson model.

Section snippets

Materials

The white crystalline solid of OTBN with a purity (as mass fraction) of 0.9941 was supplied from the Hubei Jianyuan Chemical Co., Ltd, China, which was used without further purification. The 2-propanol, 2-butanol, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, acetone and acetonitrile used in the experiments were of analytical reagent (AR) grade (purchased from Tianjin Yuxiang Technology Co., Ltd, China) and were used without further purification. The mass fraction purity of

Theoretical basis

To extend the applicability of the solubility data, the modified Apelblat equation, the Wilson model and the NRTL model were used to correlate and analyze the experimental solubility data of OTBN. Furthermore, the mixing thermodynamic properties of OTBN in different solvents were calculated based on the experimental solubility data and Wilson model.

XRPD and DSC analysis

The XRPD patterns for the raw material of crystalline OTBN and all the solid-phase OTBN in equilibrium with the studied solvents were found to be the same, which are shown in Fig. 2, Fig. 3. The results demonstrate that the crystal forms of solid OTBN have not changed during the experimental process.

The DSC analysis results of all the OTBN samples were also found to be the same, which is shown in Fig. 4. It can be seen from the DSC curve of OTBN that there is an obvious endothermic peak, the

Conclusions

In the present work, the solubility data of OTBN in eight pure solvents were determined in different temperature ranges from (268.05 to 303.25) K by using UV spectrometer method under atmospheric pressure. It was found that the solubility of OTBN increases with the rising of temperature in all the eight solvents. In the temperature range investigated, the order of OTBN solubility in these selected pure solvents is acetone > methyl acetate > ethyl acetate > propyl acetate > butyl acetate > 2-butanol > 

Notes

The authors declare no competing financial interest.

Acknowledgments

The authors are grateful to the financial supported from National Natural Science Foundation of China (No. 21376165), Key Project of Tianjin Science and Technology Supporting Programme (No. 13ZCZDNC02000) and Major National Scientific Instrument Development Project (No. 21527812).

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