Catalytic Process Design: The Industrial Perspective

4′-(Bromomethyl)-2-cyanobiphenyl (BCB) is a vital building block to various sartans, which are an important group of nonpeptide angiotensin II antagonists. The commercial manufacture of BCB from 2-cyano-4′-methylbiphenyl by Wohl−Ziegler bromination is, however, dependent on troublesome chlorinated solvents such as chlorobenzene or carbon tetrachloride. In this work, we use the response surface methodology (RSM) together with solvent principal components as an exploratory tool to identify greener solvent alternatives. We find that there is a significant interaction between solvent principal components, showing that the usual strategy of one-variable-at-a-time is not an applicable solvent selection method for this particular reaction. Based on the contour plot, we find that t 1 and t 2 of solvents should preferably be below −2 and −3, respectively, and within the outer limits of the model to find a solvent ideal for the conversion of 2-cyano-4′-methylbiphenyl into BCB, resulting in a yield of above 80%. We also find that especially carbonate esters such as propylene carbonate (experimental conversion and yield of 83.5 and 76.0%, respectively) or diethyl carbonate (experimental conversion and yield of 88.9 and 71.0%, respectively) are well predicted by the model and suitable replacements. The RSM approach together with solvent principal components is a powerful combination that may be useful for the "greening" of many other commercial important syntheses.

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Catalytic Process Design: The Industrial Perspective

Cited by 2 publications

References 128 publications

Mutagenic Impurities – Assessment of Fate and Control Options

Mutagenic Impurities – Assessment of Fate and Control Options

Multivariate Analysis in the Selection of Greener Solvents for the Bromination of 2-Cyano-4’-methylbiphenyl

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