Catalysed Reaction

The work reported in this section is concerned primarily with reaction mechanism and process studies. The use of catalysed reactions as a tool to investigate acidic oxides and zeolites is covered in the previous section. 

Chemical Reaction Engineering , Advances in Chemistry Series No. 109, American Chemical Society, Washington, 1972, p. 259. 

The distinction between stepwise and concerted processes is clear in principle even though establishing whether an overall transformation is one or the other may be problematical [ 5 ]. Once it has been established that two aspects of an overall transformation are concerted, the 

It is the coupling of the bond making between Y and C with the unbonding of X- from C in the transition structure which makes the process possible and the poorer the nucleofuge, the more necessary the coupling. Discussion of these matters was enormously facilitated by the introduction of two-dimensional reaction maps by More O Ferrall [26]. A simple case for substitution at unsaturated carbon, i.e. acetyl transfer from one Lewis base to another, is shown in Fig. 1.2. 

Whereas many reactions catalysed by organometallic compounds are characteristically different from those catalysed by Bronsted acids and bases, and to a degree their investigators have developed distinctive terminologies, the strategies employed in mechanistic studies are 

Anslyn, E.V. and Dougherty, D.A. (2004) Modern Physical Organic Chemistry. University Science Books, Mill Valley, CA. 

Carpenter, B.K. (1984) Determination of Organic Reaction Mechanisms. Wiley-Interscience, New York. Espenson, J.H. (1995) Chemical Kinetics and Reaction Mechanisms (2nd edn). McGraw-Hill, New York. Isaacs, N.S. (1995) Physical Organic Chemistry (2nd edn).Longman, Harlow. 

Many catalysts are metals, metal oxides or other simple salts, or metal complexes. For example, formation of platinum(IV) complexes involving ligand substitution is an extremely slow process, due to the kinetic inertness of this oxidation state. However, the addition of small amounts of a platinum(II) complex to the reaction mixture leads to excellent catalysis of the reaction, assigned to mixed oxidation state bridged intermediates that promote ligand transfer. 

There are also nonmetallic catalysts, of which the best known are the various forms of activated carbon. For example, isomerization of inert, chiral cobalt(in) complexes is accelerated significantly by the presence of carbon this is assigned to reduction of cobalt(III) on the surface of the carbon to labile cobalt(II), allowing rapid ligand rearrangement, with air subsequently rapidly re-oxidizing the cobalt(II) to cobalt(III) before ligand dissociative processes can become involved. 

Examples of reactions that undergo change in oxidation state are covered in more detail in the following section. 

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CF3CO2H. Colourless liquid, b.p. 72-5 C, fumes in air. Trifluoroacetic acid is the most important halogen-substituted acetic acid. It is a very strong acid (pK = o y) and used extensively for acid catalysed reactions, especially ester cleavage in peptide synthesis. 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

The mecluLnism of this base-catalysed reaction probably involves the intermediate formation of an aldol ... 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

In a Lewis-acid catalysed Diels-Alder reaction, the first step is coordination of the catalyst to a Lewis-basic site of the reactant. In a typical catalysed Diels-Alder reaction, the carbonyl oxygen of the dienophile coordinates to the Lewis acid. The most common solvents for these processes are inert apolar liquids such as dichloromethane or benzene. Protic solvents, and water in particular, are avoided because of their strong interactions wifti the catalyst and the reacting system. Interestingly, for other catalysed reactions such as hydroformylations the same solvents do not give problems. This paradox is a result of the difference in hardness of the reactants and the catalyst involved... 

Appreciating the beneficial influences of water and Lewis acids on the Diels-Alder reaction and understanding their origin, one may ask what would be the result of a combination of these two effects. If they would be additive, huge accelerations can be envisaged. But may one really expect this How does water influence the Lewis-acid catalysed reaction, and what is the influence of the Lewis acid on the enforced hydrophobic interaction and the hydrogen bonding effect These are the questions that are addressed in this chapter. 

A large number of mechanistic studies have established the mechanism of the catalysed reactions, which is... 

Scheme 2.2. Lewis-acid catalysed reactions in pure water.

Lewis-acid catalysed decarboxylatiom. Later studies have focnsed on the effects of ligands on the efficiency of the catalysed reaction" This topic will be discussed extensively in Chapter 3. 

Table 1.1. Apparent second-order rate constants for the Cii" -ion catalysed reaction of 2.4a and 2.4g with 2.5 and ratios of the rate constants for the catalysed and uncatalysed reaction in different solvents at 25 °C.

The rate constants for the catalysed Diels-Alder reaction of 2.4g with 2.5 (Table 2.3) demonstrate that the presence of the ionic group in the dienophile does not diminish the accelerating effect of water on the catalysed reaction. Comparison of these rate constants with those for the nonionic dienophiles even seems to indicate a modest extra aqueous rate enhancement of the reaction of 2.4g. It is important to note here that no detailed information has been obtained about the exact structure of the catalytically active species in the oiganic solvents. For example, ion pairing is likely to occur in the organic solvents. 

The equilibrium constants obtained using the metal-ion induced shift in the UV-vis absorption spectrum are in excellent agreement with the results of the Lineweaver-Burke analysis of the rate constants at different catalyst concentrations. For the copper(II)ion catalysed reaction of 2.4a with 2.5 the latter method gives a value for of 432 versus 425 using the spectroscopic method. 

Table 2.10. Substituent effect on the selectivity of the Cu catalysed reaction of 2.4 with 2.5 in water at25°C.

In summary, the effects of a number of important parameters on the catalysed reaction between 2.4 and 2.5 have been examined, representing the first detailed study of Lewis-acid catalysis of a Diels-Alder reaction in water. Crucial for the success of Lewis-acid catalysis of this reaction is the bidentate character of 2.4. In Chapter 4 attempts to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water beyond the restriction to bidentate substrates will be presented. 

Studies of the Diels-Alder reaction of the ionic dienophile 2.4g have demonstrated that the acpieous acceleration of the uncatalysed reaction as well as the catalysed reaction is not significantly affected by the presence of the ionic group at a site remote from the reaction centre. 

In contrast, investigation of the effect of ligands on the endo-exo selectivity of the Diels-Alder reaction of 3.8c with 3.9 demonstrated that this selectivity is not significantly influenced by the presence of ligands. The effects of ethylenediamine, 2,2 -bipyridine, 1,10-phenanthroline, glycine, L-tryptophan and L-abrine have been studied. The endo-exo ratio observed for the copper(II)-catalysed reaction in the presence of these ligands never deviated more than 2% from the endo-exo ratio of 93-7 obtained for catalysis by copper aquo ion. 

To the best of our knowledge the data in Table 3.2 constitute the first example of enantio selectivity in a chiral Lewis-acid catalysed organic transformation in aqueous solution. Note that for the majority of enantioselective Lewis-acid catalysed reactions, all traces of water have to be removed from the... 

Berezin and co-workers have analysed in detail the kinetics of bimolecular micelle-catalysed reactions ". They have derived the following equation, relating the apparent rate constant for the reaction of A with B to the concentration of surfactant ... 

The use of dienophile 5.1 also allows study of the effect of micelles on the Lewis-acid catalysed reaction. These studies are described in Section 5.2.2. and represent the first in-depth study of Lewis-acid catalysis in conjunction with micellar catalysis , a combination that has very recently also found application in synthetic organic chemistry . ... 

The enhanced binding predicts a catalytic potential for these solutions and prompted us to investigate the influence of the different types of micelles on the rate of the copper-ion catalysed reaction. Table 5.5 summarises the results, which are in perfect agreement with the conclusions drawn from the complexation studies. 

In order to obtain more insight into the local environment for the catalysed reaction, we investigated the influence of substituents on the rate of this process in micellar solution and compared this influence to the correspondirg effect in different aqueous and organic solvents. Plots of the logarithms of the rate constants versus the Hammett -value show good linear dependences for all... 

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