Transition states of acid-catalyzed reactions

This review starts with an introduction to the principles and techniques of solid-state NMR spectroscopy and the description of the most important experimental approaches for NMR investigations of solid catalysts in the working state (Sections II and III). Section IV is a summary of experimental approaches to the characterization of transition states of acid-catalyzed reactions under batch reaction conditions. 

IV. Study of Transition States of Acid-Catalyzed Reactions... 

Taft, following Ingold," assumed that for the hydrolysis of carboxylic esters, steric, and resonance effects will be the same whether the hydrolysis is catalyzed by acid or base (see the discussion of ester-hydrolysis mechanisms. Reaction 10-10). Rate differences would therefore be caused only by the field effects of R and R in RCOOR. This is presumably a good system to use for this purpose because the transition state for acid-catalyzed hydrolysis (7) has a greater positive charge (and is hence destabilized by —I and stabilized by +1 substituents) than the starting ester. 

Scheme 2.23 (a) Steric interactions in the possible transition state of 13-catalyzed Mannich-type reactions, (b) The proposed, most suitable transition state of the onh-selective Mannich-type reactions catalyzed by (/ )-3-pyrrolidinecarboxylic acid (18). 

Some time ago it was suggested by Zucker and Hammett (1939) that the behavior of the rates of acid-catalyzed reactions in moderately concentrated mineral acid (1-10m) could be used as a criterion for the degree of hydration of transition states. More recently this suggestion has been elaborated by Bunnett (1961). An acidity function, H0, analogous to pH, was defined (Hammett, 1940) by equations (19) and (20) where HI+ and I are the protonated and unprotonated forms of an... 

Antibodies raised to the transition state analogue (Fig. 7.3) will bind to the transition state of the hydrolysis reaction, lowering the activation energy and therefore catalyzing the reaction. These antibodies were trapped at the surface of a pH electrode using a dialysis membrane [Fig. 7.4(a)]. The reaction (Eq. 7.17) produces a change in local pH at the surface of the electrode, since acetic acid is one of the products. The measured pH therefore decreases as the phenyl acetate concentration increases in the external solution, since the steady-state concentration of acetic acid in the reaction layer increases [Fig. 7.4(b)]. 

Claisen rearrangement of chorismic acid 1 to prephenic acid 2 (Scheme 1), which is catalyzed by the enzyme chorismate mutase, can be considered as the key step in the biosynthesis of aromatic compounds, that is the so-called shikimic acid pathway. The chair-like transition state geometry 3 was proved by double isotope-labeling experiments [2]. However, in the laboratory this particular reaction can be accelerated not only by enzymes but also by catalytic antibodies [3]. For the generation of such antibodies haptenes such as 4 were used, that is, molecules whose structure is very similar to the transition state of the particular reaction and which are tightly bound by the antibody. 

The development of these molecular descriptors have been based on the physical model of transition states in acid-catalyzed esterification reaction of carboxylic acids and alcohols and acid hydrolysis of esters - standard reactions used by Taft for the development of Eg s empirical steric parameter in the frame of LFER (linear free energy relationship). The physical meaning of the (8, G) shape descriptors is depicted in Fig. 15.3. 

Transition States in Acid-Cataiyzed Reactions on Zeolites. A considerable number of experimental attempts were carried out to elucidate the structure of intermediates in the acid-catalyzed reactions. This information may be used to deduce the nature of elusive transition states, which are present on the catalytic surface in concentrations far below detection limit. For example, adsorption of alcohols and unsaturated hydrocarbons on acidic zeolites gives rise to the MAS NMR signal attributed to alkoxy species (135). Transition of these surface complexes to the corresponding carbenium ions, an important step in their further transformations, was shown to have low activation energy. In the synthesis of methyl-tetrabuthyl ether on zeolite Beta, features due to secondary and tertiary carbon atoms in alkoxy species have been observed. This observation along... 

Transition states in proton-catalyzed reactions that occur in zeolites and other solid acids proceed through activated intermediates close to the carbenium or carbonium ions found in superacid solutions. A carbenium ion is a positively charged ion, that can be formed by the protonation of an alkene. The positive charge is localized on an sp -hybridized C atom. A carbonimn ion is a protonated saturated alkane, that forms non-classical valencies such as a protonated a C-C bond or a five-coordinated C atom. In zeolites, the positively charged intermediates are compensated for by the negatively charged zeolite framework... 

The second example we wish to discuss is a classical of acid catalyzed reactions whose interpretation has shown the weakness of both the Zucker-Hammett hypothesis and the Bunnett w treatment. In fact, the lactonization(16) of y y oxybutyric acid follows h and gives w = 2.21 and 2,23 in HCIO and HCl, respectively, whereas the hydrolysis of Y butyrolactone(16) follows Cjj+ and gives w = 8.50 and 6.11, respectively. In other terms, the transition states for the two reactions are classified into two categories, with the water molecule being implied as nucleophile only in the latter reaction. 

The relation between kinetics and either Ho or Hr are exactly analogous to the relations of these acidity functions to equilibria because of the connection between equilibria and kinetics through transition state theory. Rates of acid-catalyzed reactions in which the transition state resembles the hydrogen-bonded protonated anilmes are correlated by the equation... 

There has been little study of the stereoselectivity of the reaction under acidic conditions. In the absence of a coordinating Lewis acid, there is no preference for a cyclic transition state. When regioisomeric enols are possible, acid-catalyzed reactions tend to proceed through the more substituted of the enols. This reflects the predominance of this enol. (See Section 7.2.)... 

Parallel reactions give rate equations having sums of rate terms. Each term provides the transition state composition for a reaction path. Eor example, some acid-catalyzed reactions have the rate equation... 

Bischler-Napieralski reaction conditions can be attributed, again, to the destabilizing ability of the trifluoromethyl group to the cationic transition state of the acid catalyzed elimination. Formation of compound 29 was ultimately accomplished by base catalyzed methanol elimination-conditions conditions that are quite unusual for isoquinoline formation. 

Nitrones are a rather polarized 1,3-dipoles so that the transition structure of their cydoaddition reactions to alkenes activated by an electron-withdrawing substituent would involve some asynchronous nature with respect to the newly forming bonds, especially so in the Lewis acid-catalyzed reactions. Therefore, the transition structures for the catalyzed nitrone cydoaddition reactions were estimated on the basis of ab-initio calculations using the 3-21G basis set. A model reaction indudes the interaction between CH2=NH(0) and acrolein in the presence or absence of BH3 as an acid catalyst (Scheme 7.30). Both the catalyzed and uncatalyzed reactions have only one transition state in each case, indicating that the reactions are both concerted. However, the synchronous nature between the newly forming 01-C5 and C3-C4 bonds in the transition structure TS-J of the catalyzed reaction is rather different from that in the uncatalyzed reaction TS-K. For example, the bond lengths and bond orders in the uncatalyzed reaction are 1.93 A and 0.37 for the 01-C5 bond and 2.47 A and 0.19 for the C3-C4 bond, while those in... 

The Lewis acid-catalyzed reaction of nitrone 21 with ethyl vinyl ether 22 (Scheme 8.8) was also investigated for BH3 and AlMe3 coordinated to 21 [32]. The presence of BH3 decreases the activation energy for the formation of 23 by 3.1 and 4.5 kcal mol to 9.6 kcal mol for the exoselective reaction and 11.6 kcal-mol for the endo-selective reaction, respectively, while the activation energy for the formation of 24 increases by >1.4 kcal mol , compared to those for the uncatalyzed reaction. The transition-state structure for the BH3-exo-selective 1,3-dipolar cycloaddition reaction of nitrone 21 with ethyl vinyl ether 22 is shown in Fig. 8.19. 

Both these methods require equilibrium constants for the microscopic rate determining step, and a detailed mechanism for the reaction. The approaches can be illustrated by base and acid-catalyzed carbonyl hydration. For the base-catalyzed process, the most general mechanism is written as general base catalysis by hydroxide in the case of a relatively unreactive carbonyl compound, the proton transfer is probably complete at the transition state so that the reaction is in effect a simple addition of hydroxide. By MMT this is treated as a two-dimensional reaction proton transfer and C-0 bond formation, and requires two intrinsic barriers, for proton transfer and for C-0 bond formation. By NBT this is a three-dimensional reaction proton transfer, C-0 bond formation, and geometry change at carbon, and all three are taken as having no barrier. 

The active site of an enzyme is generally a pocket or cleft that is specialized to recognize specific substrates and catalyze chemical transformations. It is formed in the three-dimensional structure by a collection of different amino acids (active-site residues) that may or may not be adjacent in the primary sequence. The interactions between the active site and the substrate occur via the same forces that stabilize protein structure hydrophobic interactions, electrostatic interactions (charge-charge), hydrogen bonding, and van der Waals interactions. Enzyme active sites do not simply bind substrates they also provide catalytic groups to facilitate the chemistry and provide specific interactions that stabilize the formation of the transition state for the chemical reaction. 

Figure 5-7. Transition state of amino acid salt catalyzed Diels-Alder reaction. Reprinted with permission by Am. Chem. Soc., Ref. 34.

HS may alter the reactivities of bound substrates in a way similar to that of anionic surfactants (inhibiting base-catalyzed and accelerating acid-catalyzed reactions). These effects were attributed to electrostatic stabilization of the transition state for the acid catalysis in which the substrate becomes more positively charged, and to destabilization of the transition state for base-catalyzed hydrolysis in which the substrate becomes more negatively charged. 

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