(179f) Vapor Liquid Equilibrium of Phenylacetylcarbinol

R-Phenylacetylcarbinol (PAC), a chiral precursor, is an active pharmaceutical ingredient in manufacturing of various drugs such as ephedrine, adrenaline, etc. It is currently produced by means of biotransformation of benzaldehyde and pyruvate through whole cell fermentation using baker's yeast.¹ To achieve a better partitioning of PAC from aqueous to organic phase in the final step of the production process, it is important to know the physical and thermodynamic properties such as density, vapor pressure, boiling point, critical temperature, critical pressure, heat of vaporization, etc. As the only experimental data point available for PAC in literature² is the normal boiling point, we report the physical and thermodynamic properties as predicted through structure property correlations and molecular simulations. This is the first step towards predicting properties of solutions of PAC with other compounds present in the reactor. 

Qualitative structure property correlations facilitate the prediction of physical properties from the structure of a molecule. A group contribution based Marrero-Gani (MG) method³ has been employed to determine the boiling point and the critical properties of PAC. The normal boiling point obtained from MG method was around 75 K higher than the experimentally reported value of 479 K. Further, by making use of the predicted critical property data, the vapor liquid equilibrium has been determined using various equations of state⁴ such as, Soave-Redlich-Kwong, Peng-Robinson, and volume translated Peng-Robinson.

Molecular simulations give a quantitative insight on various physical and thermodynamic properties within the limitations of the forcefield and its parameters. Constant volume Gibbs ensemble Monte Carlo (GEMC-NVT) simulations have been performed using MCCCS towhee package⁵ in a temperature range of 350 K to 600 K, to determine  pure component VLE and critical point of PAC.The transferable potentials for phase equilibria -united atom (TraPPE-UA) forcefield⁶ developed by the Siepmann's group has been employed in the current study.The missing torsional profiles of various groups were obtained from density functional theory analysis at the B3PW91/6-31++G(d,p) level of theory using Gaussian03 package⁷. The boiling point predicted was determined to be 510 K, which lies between the prediction of the MG method and that reported from experiment. The VLE from GEMC-NVT is compared with the equation of state approach. The liquid and vapor densities at coexistence and the critical point data from both the methods are found to be in good agreement. The properties predicted include liquid and vapor coexistence densities, enthalpy of vaporization, saturation pressure, boiling point and critical properties. 

References

1.           Rosche, B., Sandford, V., Breuer, M., Hauer, B. & Rogers, P. L. Enhanced production of R-phenylacetylcarbinol (R-PAC) through enzymatic biotransformation. Journal of Molecular Catalysis B: Enzymatic 19-20, 109–115 (2002).

2.           Chapman & Hall. Dictionary of organic compounds. 6^th edition, CRC press: New York, (1995).

3.           Marrero, J. & Gani, R. Group-contribution based estimation of pure component properties. Science 184, 183–208 (2001).

4.           Schmid, B. & Gmehling, J. From van der Waals to VTPR: The systematic improvement of the van der Waals equation of state. The Journal of Supercritical Fluids 55, 438–447 (2010).

5.           MCCCS Towhee. Available at: http://towhee.sourceforge.net.

6.           Keasler, S. J., Charan, S. M., Wick, C. D., Economou, I. G. & Siepmann, J. I. Transferable Potentials for Phase Equilibria − United Atom Description of Five- and Six-Membered Cyclic Alkanes and Ethers. The Journal of Physical Chemistry B 116, 11234-11246  (2012).

7.             M. J. Frisch et al., GAUSSIAN 03, Revision C.01, Gaussian, Inc., Walling- ford, CT, 2004.