Managing Competing Reactions

Varying Conditions

The yield of a desired reaction transformation in an organic synthesis can often be reduced by the loss of a portion of the starting material in a competing reaction or reactions. The standard strategy then is to vary the reaction conditions including most prominently the reaction time, the reaction temperature, and the solvent. The logic is that each different reaction course is likely to respond differently to changes, so there is a good chance that conditions can be found where the desired reaction is increasingly favoured.

 Common Trail Changes

A change in the solvent aims to change the difference in the free energies of activation between the different reactions. A change in reaction temperature aims to change the ratio of reaction rates as a function of temperature without changing the actual difference in free energies of activation. A change in reaction time targets the difference in rates directly. A change in the stoichiometry of the starting materials is aimed at discovering a difference in the molecularity of the competing reactions.

Catalysis

There are other less obvious but potentially effective targets. If catalyzed versions of the desired reaction are known or can be conceived, addition of a catalyst can accelerated the desired transformation relative to alternative outcomes. Addition of a catalyst is the most dramatic way to change one free energy of activation relative to another. Furthermore, because catalytic mechanisms are specific in many cases, it is much less likely that both reactions would be affected.

A much, much, less frequent situation arises where the less favoured reaction can be inhibited. Such a rarer situation has been described in the paper, Effect of Amines on O-Benzyl Group Hydrogenolysis,[ Bronislaw P. Czech and Richard A. Bartsch, J. Org. Chem. 1984, 49, 4076-4078 ].As the example, a substance containing both a monosubstituted olefin and an alkyl benzyl ether was treated with hydrogen gas and Pd/C in alcohol with the addition of a non-stoichiometric amount of a non-aromatic amine. In the presence of the added amine only olefin reduction occurred. Benzyl n-nonyl ether was investigated as a test substrate. Using the same conditions but in one case in the presence of 5 mol % n-butylamine and in the other in its absence, the first case gave complete debenzylation and the latter case gave none. This may be a fairly common case in the situation of competing reactions on heterogeneous catalysts. If different sites are responsible for the catalysis of the two reactions one group of sites can be selectively poisoned. Thus we can understand the differing activities of a catalyst prepared with different protocols.

Different Fates of a Common Intermediate

How would one create larger differences in the product ratios arising from differing fates of a common intermediate?

This is the most troublesome situation because there is a common free energy of activation going to the common intermediate so changing that activation energy will not change a product mixture. Also, any subsequent free energies of activation passing from the high energy common intermediate to the transition states will be small and the difference between these two even smaller. It is the rate of quenching of the activated common intermediate that may be crucial here. Take the example of the 5-hexenyl radical. After only a brief existence the material trapped will arise from the cyclopentylmethyl radical.