Kinetically controlled process

Hthiated 4-substituted-2-methylthia2oles (171) at -78 C (Scheme 80). Crossover experiments at—78 and 25°C using thiazoles bearing different substituents (R = Me, Ph) proved that at low temperature the lithioderivatives (172 and 173) do not exchange H/Li and that the product ratios (175/176) observed are the result of independent metala-tion of the 2-methyl and the C-5 positions in a kinetically controlled process (444). At elevated temperatures the thermodynamic acidities prevail and the resonance stabilized benzyl-type anion (Scheme 81) becomes more abundant, so that in fine the kinetic lithio derivative is 173, whereas the thermodynamic derivative is 172. 

It was clearly shown by NMR spectroscopy that the addition of ammonia or primary or secondary alkylamines at position 5 of the 1,2,4-triazine 4-oxides to give the adducts 89 is a kinetically controlled process, while addition at position 3 to form the ring-opening products 85 is a thermodynamically controlled process. 

S-D-Xylosidase in extract from Trichoderma reesei Transxylosylation with methyl-/i-xyloside and 1 -butanol Butanol-acetate buffer pH 4.5 Kinetically controlled process 128... 

The anti addition is a kinetically controlled process that results from irreversible backside opening of an iodonium ion intermediate by the carboxylate nucleophile. Bartlett and co-workers showed that the more stable trans product was obtained under acidic conditions in which there is acid-catalyzed equilibration (thermodynamic control).74... 

The first of the few low-temperature methods for the formation of an o-QM was a method developed by Rokita.5 It is principally used for reversible DNA alkylation. However, it has recently begun to find its way into some synthetic applications. It utilizes a silylated phenol, which proves vastly more manageable as an o-QM precursor than the corresponding o-hydroxyl benzyl halide (Fig. 4.6). In this kinetically controlled process, expulsion of a benzylic leaving group is triggered at low temperature by treatment with a fluoride ion, which causes a (3-elimination. 

Substituted adducts similar to 50 have been obtained from the reactions carried out in chlorobenzene and in toluene 19>. Whereas methanesulphonyl azide does not thermolyze appreciably below 120 °C, when a solution of CH3SO2N3 in benzene was heated at 80 °C for 100 hr, 47 (ca. 0.5%) could be detected by thin layer chromatography but no 49 38>. Almost all the azide remained undecomposed. Similarly, very small, amounts of 47 were observed, together with much tar and undecomposed azide, on photolysis of CH3SO2N3 in benzene at room temperature or at 80 °C 10). This confirms that azepine formation is the kinetically controlled process, while the anilides are the products of thermodynamic control. 

Although the principal stereoisomer formed at ambient temperatures in the hydrogenation of disubstituted benzenes has the cis configuration, trans isomers are also produced, the amount being a function of the structure of the substrate, the pressure of hydrogen, the temperature, and the catalyst (97-100). Mixtures are formed although the products are virtually unaffected under these conditions consequently the trans isomers result from a kinetically controlled process. 

Considering kinetically controlled process at the electrode surface without lateral interactions between immobilized species, the following form of the Butler-Volmer equation holds ... 

As discussed above, proteases are peptide bond hydrolases and act as catalysts in this reaction. Consequently, as catalysts they also have the potential to catalyze the reverse reaction, the formation of a peptide bond. Peptide synthesis with proteases can occur via one of two routes either in an equilibrium controlled or a kinetically controlled manner 60). In the kinetically controlled process, the enzyme acts as a transferase. The protease catalyzes the transfer of an acyl group to a nucleophile. This requires an activated substrate preferably in the form of an ester and a protected P carboxyl group. This process occurs through an acyl covalent intermediate. Hence, for kineticmly controlled reactions the eii me must go through an acyl intermediate in its mechanism and thus only serine and cysteine proteases are of use. In equilibrium controlled synthesis, the enzyme serves omy to expedite the rate at which the equilibrium is reached, however, the position of the equilibrium is unaffected by the protease. 

When one or more molecular entity(ies) participates in two or more parallel and irreversible reactions in which different products are formed, the faster-forming product will accumulate by the reaction having the lowest activation energy. Thus, kinetically controlled processes are those whose proportion of products is governed by the relative rates of the competing reactions. If the reac-... 

Polymerization of optically active isonitiiles, 72, also leads to the formation of helical polymers with a preferential screw sense (219-222). Various factors distinguish this system from the preceding ones In the isonitrile case no new stereogenic atoms are formed during polymerization the helices are rigid and there is no indication of conformational equilibrium in the system the formation of a preferential screw sense is very probably a kinetically controlled process. 

In Figure 10.1 the time course of thermodynamically and kinetically controlled processes catalysed by biocatalysts are compared. The product yield at the maximum or end point is influenced by pH, temperature, ionic strength, and the solubility of the product. In the kinetically controlled process (but not in the thermodynamically controlled process) the maximum yield also depends on the properties of the enzyme (see next sections). In both processes the enzyme properties determine the time required to reach the desired end point. The conditions under which maximum product yields are obtained do not generally coincide with the conditions where the enzyme has its optimal kinetic properties or stability. The primary objective is to obtain maximum yields. For this aim it is not sufficient to know the kinetic properties of the enzyme as functions of various parameters. It is also necessary to know how the thermodynamically or the kinetically controlled maximum is influenced by pH, temperature and ionic strength, and how this may be influenced by the immobilization of the biocatalysts on different supports. 

Eqnation 10.4 shows that this ratio increases with the nucleophile content. Experi-mental data for some transferases and hydrolases are given in Table 10.2. Using these data and a water concentration of 55 M, Equation 10.4 predicts that a high product yield, in kinetically controlled processes catalyzed by hydrolases, require nucleophile concentrations >0.1 M. These are much higher than substrate concentrations in vivo. 

For the temperature dependence of the maximum yield in kinetically controlled processes, detailed data are generally not available. In all cases, where this has been studied experimentally, a decrease in the maximum product yield with increasing temperature is observed (Kasche, 1986). 

Several kinetically controlled processes are already used on an industrial scale, such as the conversion of porcine or recombinant proinsulin to human insuhn and the conversion... 

On the basis of these considerations, proton abstraction in 3-fluoropyridine using n-BuLi/TMEDA complex in THF is expected to occur at the most acidic C4 site, as observed. On the other hand, in Et20, which is a more weakly basic solvent than THF, coordination of base with ring nitrogen (87) is favored and leads by a proximity effect to C2-proton abstraction and formation of 83 (Scheme 24). Addition of THF to a solution of 83 in Et20 at -60°C did not result in the formation of the isomeric species 84, thus suggesting that C4-lithiation in THF is a kinetically controlled process that does not proceed via the 2-lithiated species 83. 

These approaches can be divided into two groups. In the first group, fast chemistry (approaches 1 and 2), it is assumed that the rate of chemical conversion is not kinetically controlled. The second group,finite rate chemistry (approaches 3-5), allows for kinetically controlled processes, in that restrictions are put on the chemical reaction rate. Below we discuss these different approaches in more detail. 

Here rmix is a characteristic mixing time for the system, while rreac is a characteristic time for the chemical reaction. If the Damkohler number has a value much larger than unity, the process is diffusionally controlled a value much lower than 1 indicates a kinetically controlled process. The terms in the Damkohler number may be defined in different ways, according to the physical characteristics of the system of interest. 

What are the reaction kinetics of each of the kinetically controlled processes ... 

Brown s one-pot synthesis54" affords mainly (19S)-heteroyohimbine alkaloids (e.g. tetrahydroalstonine) by a kinetically controlled process involving preferential formation of an ( )-alkene (61 ) from the initially formed dienamine... 

Specific dehydrogenation at the terminal positions of alkanes is a reaction that would be of high utility. The 1-alkenes obtained by such a reaction are the basis of a variety of additional products. Felkin and co-workers discovered that metal complexes are able to mediate the transfer of hydrogen from alkanes 13 to olefins 14 (Scheme 4) [17]. The specific advantages of a transition metal catalyst can be applied to the benefit of the chemoselectivity of this reaction. In a kinetically controlled process, it is predominantly primary C-H bonds that add to the metal complex. A subsequent /Miydride elimination affords the terminal alkenes... 

Exploring different methods for the intramolecular radical cyclization of 78 (Scheme 15)95, Usui and Paquette observed that (TMS SiH under normal conditions affords the expected functionalized diquinane 79 in 80% yield and in a a fi ratio of 82 18. MM2 calculations suggest it is the result of a kinetic controlled process. It is worth mentioning that the endothermic reaction 42 is expected to be one of the propagation steps in this chain process (vide infra). By replacing the silane with tin hydride under similar experimental conditions, the unexpected product 80 was obtained in a 77% yield. 

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