Thermodynamic control of product

Specific alterations of the relative reactivity due to hydrogen bonding in the transition state or to a cyclic transition state or to electrostatic attraction in quaternary compounds or protonated azines are included below (cf. also Sections II, B, 3 II, B, 5 II, C and II, F). A-Protonation is often reflected in an increase in JS and therefore the relative reactivity can vary with the significance of JS in controlling the reaction rate. Variation can also result from rate determination by the second stage of the SjjAr2 mechanism or from the intervention of thermodynamic control of product formation. Variation in the rate and in the reactivity pattern of polyazanaph-thalenes will result when nucleophilic substitution [Eq. (10)] occurs only on a covalent adduct (408) of the substrate rather than on its aromatic form (400). This covalent addition is prevented by any 4-... 

FIGURE 6.3 Free energy profile illustrating kinetic versus thermodynamic control of product. The starting compound (A) can react to give either B or C. 

In most cases, more 1,4- than 1,2-addition product is obtained. This may be a consequence of thermodynamic control of products, as against kinetic. In most cases, under the reaction conditions, 15 is converted to a mixture of 15 and 16, which is richer in 16. That is, either isomer gives the same mixture of both, which contains more 16. It was found that at low temperatures, butadiene and HCl gave only 20-25% 1,4 adduct, while at high temperatures, where attainment of equilibrium is more likely, the mixture contained 75% 1,4 product. 1,2 Addition predominated over 1,4 in the reaction between DCl and 1,3-pentadiene, where the intermediate was the symmetrical (except for the D label) HjCHC—CH—CHCH2D. Ion pairs were invoked to explain this result, since a free ion would be expected to be attacked by Cl equally well at both positions, except for the very small isotope effect. 

Product stabilities, and kinetic and thermodynamic control of product formation... 

We shall consider reactions catalysed by two different types of pro-catalyst the first (type A) employs Pd-allyl cations ([Pd(a]lyl)(PCy3)]+/Et3SiH or [Pd(allyl)(MeCN)2] + ), and the second (type B) employs Pd-alkyl or chloro complexes ([(phen)Pd(Me)(MeCN)]+, where phen = phenanthroline, and [(RCN)2PdCl2]). These two types of catalysts give very different products in the cyclo-isomerisation of typical 1,6-dienes such as the diallyl-malonates (10), Scheme 12.6. Since there is known to be a clear order of thermodynamic stability 11 < 12 <13, with a difference of ca. 3-4 kcal mol 1 between successive pairs, any isomerisation of products under the reaction conditions will tend towards production of 12 and 13 from 11 and 13 from 12. Clearly, when 11 is the major product (as with pro-catalysts of type A), it must be the kinetic product (see Chapter 2 for a discussion of kinetic and thermodynamic control of product distributions). However, when 12 is generated selectively, as it is with pro-catalysts of type B, there is the possibility that this is either generated by rapid (and selective) isomerisation of 11 or generated directly from 10. 

Similarly, reaction of chlorobenzene with isopropyl chloride imder Friedel—Crafts conditions produced primarily the ortho and para alkylation products after a short reaction period. Allowing the reaction mixture to stand for a week before workup, however, produced primarily the meta product. In both of these cases, the product isolated after a short time is said to be the product of kinetic control of the product distribution, since the product isolated is the one that is formed faster. The product isolated after a longer time is said to be the product of thermodynamic control of product distribution, since it is the more stable product. ... 

The reversibility and thermodynamic control of product formation found for the high-pressure reaction between glycals and tosyl isocyanate indicated that the [2+2]cycloaddition of isocyanates to glycals could occur at atmospheric pressure under specific reaction conditions including an excess of isocyanate, as well as proper selection of solvent and substrates. Acyl isocyanates are generally less reactive in [2+2]cycloaddition reactions than sulfonyl isocyanates, except for trichloro- and trifluoroacetyl isocyanate 10,12 addition, acyl isocyanates are problematic because of the competitive formation of [4+2]cycloadducts, which are usually thermodynamically preferred over the [2+2]cycloadducts. 

Why do the nucleophiles listed in Table 19.1 react with conjugated carbonyl compounds by 1,4-addition rather than 1,2-addition The answer has to do with kinetic control versus thermodynamic control of product formation. It has been shown that 1,2-addition of nucleophiles to the carbonyl carbon of a, 8-unsaturated carbonyl compounds is faster than conjugate addition. If formation of the 1,2-addition product is irreversible, then that is the product observed. If, however, formation of the 1,2-addition product is reversible, then an equilibrium is established between the more rapidly formed but less stable 1,2-addition product and the more slowly formed but more stable 1,4-addition product. As mentioned at the beginning of the chapter, a carbon-oxygen double bond is stronger than a carbon-carbon double bond. Thus, under conditions of thermodynamic (equilibrium) control, the more stable 1,4-Michael addition product is formed. 

Mudu, F., Arstad, B., EjeUvag, H., et al. (2011). Thermodynamic Control of Product Formation During the Reaction Between CH4 and Pt Promoted Ceria-zirconia Solid Solutions, Catal. Lett., 141, pp. 8-14. 

Generally, the sulfonation of naphthalene leads to a mixture of products. Naphthalene sulfonation at less than ca 100°C is kineticaHy controlled and produces predominandy 1-naphthalenesulfonic acid (4). Sulfonation of naphthalene at above ca 150°C provides thermodynamic control of the reaction and 2-naphthalenesulfonic acid as the main product. Reaction conditions for the sulfonation of naphthalene to yield desired products are given in Figure 1 alternative paths are possible. A Hst of naphthalenesulfonic acids and some of their properties is given in Table 1. 

Product composition may be governed by the equilibrium thermodynamics of the system. When this is true, the product composition is governed by thermodynamic control. Alternatively, product composition may be governed by competing rates of formation of products. This is called kinetic control. 

Thermodynamic Versus Kinetic Control of Product Distributions. 228... 

Similar results are obtained from incineration of polymeric materials with octabromo- and pentabromodiphenyl ether (refs. 11,12). The temperature with the maximum PBDF-yield depends on the kind of polymeric matrix. All three bromo ethers 1-2 give the same isomer distribution pattern with preference for tetrabrominated dibenzofiirans. The overall yield of PBDF is lower for incineration of pentabromobiphenyl ether 2, 4 % at 700°C compared to 29 % for ether 1 at 500 °C (ref. 12). The preferred formation of tetrabrominated fiirans observed at all temperatures cannot be a result of thermodynamic control of the cyclisation reaction it is likely due to the special geometry of the furnaces. One explanation is that a spontaneous reaction occurs at approximately 400°C while the pyrolysis products are transferred to the cooler zones of the reactor details can be found elsewhere (ref. 12). 

Figure 6.3 shows a free energy profile for a reaction in which B is thermodynamically more stable than C (lower AG), but C is formed faster (lower AG ). If neither reaction is reversible, C will be formed in larger amount because it is formed faster. The product is said to be kinetically controlled. However, if the reactions are reversible, this will not necessarily be the case. If such a process is stopped well before the equilibrium has been established, the reaction will be kinetically controlled since more of the faster-formed product will be present. However, if the reaction is permitted to approach equilibrium, the predominant or even exclusive product will be B. Under these conditions, the C that is first formed reverts to A, while the more stable B does so much less. We say the product is thermodynamically controlled.Of course. Figure 6.3 does not describe all reactions in which a Compound A can give two different products. In many cases, the more stable product is also the one that is formed faster. In such cases the product of kinetic control is also the product of thermodynamic control. 

Whether nucleophilic addition is predominantly conjugate (1,4-) or to C=0 may depend on whether the reaction is reversible or not if it is reversible, then the control of product can be thermodynamic (equilibrium cf. p. 43), and this will favour 1,4-addition. This is so because the C=C adduct (98) obtained from 1,4-addition will tend to be thermodynamically more stable than the C=0 adduct (99), because the former contains a residual C=0 n bond, and this is stronger than the residual C=C n bond in the latter ... 

Free radical addition of HBr to buta-1,2-diene (lb) affords dibromides exo-6b, (E)-6b and (Z)-6b, which consistently originate from Br addition to the central allene carbon atom [37]. The fact that the internal olefins (E)-6b and (Z)-6b dominate among the reaction products points to a thermodynamic control of the termination step (see below). The geometry of the major product (Z)-(6b) has been correlated with that of the preferred structure of intermediate 7b. The latter, in turn, has been deduced from an investigation of the configurational stability of the (Z)-methylallyl radical (Z)-8, which isomerizes with a rate constant of kiso=102s 1 (-130 °C) to the less strained E-stereoisomer (fc)-8 (Scheme 11.4) [38]. 

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