Mixing and the selectivity of fast chemical reactions

Abstract

The problemAmong the problems that arise in the scale-up of batch reactions is that of reactions whose outcome is sensitive to mixing. While many reactions do not exhibit such sensitivity, those that do can exhibit substantial yield loss on scale-up.It is the main purpose of this chapter to describe recent advances in understanding the interactions between the physical operation of mixing reagents and the distribution of products from fast reactions. Whereas much is known about the chemical factors influencing the yield of a particular product, the role of mixing is often less clear. This yield should be high when k[ » k2 and when the stoichiometric ratio (number of moles of B charged to the reaction vessel per mole of A) is around unity. (If this ratio equals or exceeds two, R will be fully converted to S as the reactions run to completion.) Experiments on the single-phase nitration of durene (l,2,4,5-tetramethylbenzene) contradicted these chemically based predictions. Although k[ is orders of magnitude greater than k 2 , measured yields of mononitrodurene (R) were much smaller than those of dinitrodurene (S) [1,2]. The yields of Rand S were increased and decreased, respectively, by increasing the intensity of agitation in the reaction vessel and by measures which retarded the reactions. Increases in the yield of the intermediate (R) as the agitation intensity was raised were also observed in the iodination of I-tyrosine [3], the bromination of 1,3,5-trimethoxybenzene [4] and in some diazo couplings to be discussed in detail later. Some competitive-consecutive reactions are characterized by k[ = 2k2 and the maximum yield of R will be 50% when the stoichiometric ratio of B to P. N. Sharratt (ed.), Handbook of Batch Process Design

Scalable Reactor Design for Pharmaceuticals and Fine Chemicals Production. 1: Potential Scale-up Obstacles

“…On a more rapid time scale is micromixing which is mixing (by molecular diffusion or fluid engulfment) on the smallest scale of motion also known as the Kolmogoroff scale, where, even in a highly turbulent fluid (with strong velocity fluctuations), the flow is no longer turbulent but laminar. Depending on the reaction time scale (e.g., a short reaction half-life) the product distribution could be affected by changes due to micro-, meso-, or macromixing on scale-up. − Whereas macromixing is concerned with the blending time for the whole solution and is of the order of seconds to minutes, meso- and micromixing time scales are of the order of milliseconds …”