Andrew V. Zeigarnik

Oxidative carbonylation of phenylacetylene catalyzed by Pd(II) and Cu(I): Experimental tests of forty-one computer-generated mechanistic hypotheses

Abstract We describe an experimental study of the reaction mechanism of phenylacetylene oxidative carbonylation to methyl ester of phenylpropiolic acid catalyzed by Pd(II) and Cu(I), PhCCH+CO+MeOH+2NaOAc+2CuCl 2 →PhCCCOOMe+2AcOH+2NaCl+2CuCl, which was closely guided by recent computational research on the generation of reaction mechanisms. Our initial mechanistic studies of this reaction were based on informal (non-computer-generated) mechanistic hypotheses. When experiments at 20°C and 1 atm led us to reject four of five mechanistic possibilities for the reaction, we turned to formulating new hypotheses with the aid of the computer programs ChemNet, which generated a reaction network consisting of 233 elementary steps, and MECHEM, which uncovered 41 simplest hypothetical pathways from within the reaction network. Our subsequent analysis of these 41 hypothetical mechanisms suggested a highly informative experiment based on the CH 3 OH/CH 3 OD kinetic isotope effect. The ratio between the rates of ester formation in nondeuterated and deuterated methanol was close to unity, suggesting that O–H bond scission occurs after the rate-limiting transmetalation step CuCCPh+PdCl 2 →ClPdCCPh+CuCl. This experiment led to rejecting 32 out of the 41 hypotheses. Four more mechanisms were rejected based on the results of preliminary experimental studies. Further work is needed to discriminate among the five remaining mechanisms.

Interactive elucidation (without programming) of reaction mechanisms in heterogeneous catalysis

MECHEM is a computer program for the interactive elucidation of reaction mechanisms. A recent application to a model catalytic system (ethane hydrogenolysis to produce methane over a transition metal catalyst) turned up a simple, plausible and seemingly novel mechanism. However, that application required some programming on the part of the user and also required subdividing the reaction into two stages in order to handle the reaction complexity. Recent advances in MECHEM now enable straightforward handling of such complex reactions without any programming nor division into stages. The capability is illustrated on the previous ethane hydrogenolysis example.

Application of Graph Theory to Chemical Kinetics. 3. Topological Specificity of Multiroute Reaction Mechanisms

A structural analysis and classification of the reaction networks of the multiroute reactions is made using the bipartite graph method. Simple submechanisms of the overall reaction mechanism are defined, so as to correspond to routes with minimal stoichiometric numbers. The possibility for balancing the intermediate species is advocated as the major classificational criterion which discriminates three categories of multiroute mechanisms:  balanced, partially balanced, and unbalanced ones. Balanced mechanisms are further classified according to the number and topological type (catalytic and noncatalytic, C- and N-type, respectively) of the simple submechanisms. The common classes of purely catalytic, noncatalytic conjugated, and chain reactions appear with distinct mechanistic topology, as do the subclasses of nonbranched and branched chain reactions.

Systematic prediction of the products and intermediates of isotopic labeling in reaction pathway studies

Isotopic labeling experiments can be highly informative in reaction pathway studies, but inferring the implications of a mechanistic hypothesis can be difficult, especially in the case of complex reactions. We report systematic methods for predicting the distribution of labeled products and intermediates given: (1) a mechanistic hypothesis; and (2) a proposed labeling experiment. The methods have been implemented with MECHEM—a computer aid for elucidating reaction mechanisms. As an illustration, we predict the outcomes of ethylene and propylene hydrogenation and n‐heptane dehydrocyclization, for a variety of mechanisms and labeling experiments. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 741–753, 1998

How Hard Is Mechanism Elucidation in Catalysis? Combinatorial Analysis of C1 Chemistry

Most chemical reactions occur over multiple steps whose identity is elucidated by experiment, yielding a reaction mechanism. Knowledge of cognitive science suggests that mechanism elucidation can be viewed as a knowledge-guided search within a combinatorial space. The MECHEM computer program searches this space comprehensively for the simplest plausible mechanisms. We use MECHEM to find mechanisms for Fischer-Tropsch chemistry and CO2 re-forming of methane, both heterogeneous catalytic reactions of current importance. The results reveal hundreds of equally simple mechanisms consistent with evidence. Hence, mechanism elucidation in catalysis is a much harder problem than is ordinarily realized.