Thermodynamics vs. kinetics

Conra.d-Limpa.ch-KnorrSynthesis. When a P-keto ester is the carbonyl component of these pathways, two products are possible, and the regiochemistry can be optimized. Aniline reacts with ethyl acetoacetate below 100°C to form 3-anilinocrotonate (14), which is converted to 4-hydroxy-2-methylquinoline [607-67-0] by placing it in a preheated environment at 250°C. If the initial reaction takes place at 160°C, acetoacetanilide (15) forms and can be cyclized with concentrated sulfuric acid to 2-hydroxy-4-methylquinoline [607-66-9] (49). This example of kinetic vs thermodynamic control has been employed in the synthesis of many quinoline derivatives. They are useful as intermediates for the synthesis of chemotherapeutic agents (see Chemotherapeuticsanticancer). 

The control of kinetic vs thermodynamic product formation can often be achieved by suitable modification of reaction conditions. A far more difficult task is to switch from the formation of a favoured major product to a disfavoured minor product, especially when the transition states for the two processes share most features in common. This challenge has been met by antibodies with considerable success, both for reaction pathways differing in regioselectivity and also for ones differing in stereoselectivity. In both situations, control of entropy in the transition state must hold the key. 

The product distribution may depend on the reaction conditions if the nucleophilic attack is reversible (kinetic vs. thermodynamic control). An additional complication arises from... 

The influence of the temperature. It has been established that the temperature has a dramatic effect on the occurrence of the Sn(ANRORC) process. Whereas participation of the Sn(ANRORC) mechanism in the amino-debromination of 4-t-butyl-6-bromopyrimidine at -75°C was found to occur for 77% according to the Sn(ANRORC) mechanism (79RTC5), it decreased to 33% when the amination was carried out at -33°C. Apparently at -75°C attack of the amide ion on C-2 is clearly favored over attack on C-6 (kinetic vs thermodynamic control) (78TL3841). Notice that 4-t-butyl-6-chloropyrimidine, when aminated at -33°C, reacts for nearly the... 

Kinetically vs thermodynamically favored a-adduct formation is not an uncommon phenomenon it has, for example, also been observed in solutions of 2-chloro-3,5-dinitropyridine in liquid ammonia containing potassium amide (85JOC484) and in the a-adduct formation between quinoline and potassium amide in liquid ammonia (73JOC1947). 

Another example of kinetic vs thermodynamic control is observed in an NMR-spectroscopic study of the ring opening of several 1-methoxy-3-carbamoylpyridinium salts by liquid ammonia. The study shows that... 

Tautomerism Kinetic vs. Thermodynamic Stability Protonation Sites in Conjugated Molecules N/N Alternatives. ... 

Furthermore, the organic functionalization studies have indicated that multiple reaction products can form even for simple systems. Kinetic and thermodynamic influences must be considered in any analysis of the product distribution. Moreover, the studies have revealed differences in the dominance of kinetic vs. thermodynamic control between the silicon and germanium surfaces. The dissimilarity primarily stems from the fact that adsorbate bonds are usually weaker on Ge than on Si. This difference in energetics leads to observable differences in the degree of selectivity that can be achieved on the two surfaces. Another important motif is the significance of interdimer bonding in the products. Many molecules, even as small as ethylene, have been observed to form products that bridge across two dimers. Consequently, each analysis of adsorption products should include consideration of interdimer as well as intradimer species. 

This review covers the Pd(0)-catalyzed allylations of aromatic ambident heterocyclic compounds, including all rings for which an aromatic tautomeric or resonance form can be written. Cases of C vs. O, C vs. N, N vs. O, and S vs. N allylation are discussed from all available viewpoints regioselectivity, kinetic vs. thermodynamic control, mechanism, stereo-... 

A similar temperature dependency was also observed with the l,x-naphthyridines (x = 5, 7). Dissolving 1,5-naphthyridine in liquid ammo-nia/potassium amide at —40°C, a very rapid formation of the C-2 adduct was observed (78JOC1673, 83AHC(33)95). At +10 °C the NMR spectrum was drastically changed and clearly showed the presence of the thermodynamically more stable C-4 adduct. This concept of kinetically vs. thermodynamically favored formation explains the controversial results in the amide-induced amination of 1,5-naphthyridine (68JOC1384, 70JHC593). 

Understand the concept of kinetic vs. thermodynamic control of reactions. 

Norton and coworkers noticed significant differences in diastereoselectivity for formation of EBTHI zirconaaziridines 17m under kinetic vs thermodynamic conditions. In general, 17m was prepared by heating the (EBTHI)zirconium methyl amide complex at 70 °C (Scheme 3). Use of a 20-fold excess of carbonate, by accelerating insertion relative to diastereomer equilibration, permitted... 

Subsequent to the report by Hall et al. (1986), a number of other groups have utilized the information on the kinetic vs thermodynamic crystallizations in polymorphic potential nonlinear optical materials to generate active materials. Black et al. (1993)... 

THE AVAILABILITY OF A REACTION CHANNEL. KINETIC VS. THERMODYNAMIC CONTROL... 

Suitably substituted isoxazolidines can undergo a thermally induced cycloreversion to nitrone and alkene. For example, the adducts of nitrones with alkylidene malonates or tolylsulfinylfuran-2(577)-ones suffer an easy cycloreversion, which determines significant changes in the diastereomeric composition of the cycloaddition mixtures depending on the reaction conditions (kinetic vs. thermodynamic control) <20040L1677, 2005JOC8825>. 

Wipf, P., Takahashi, H., Zhuang, N. Kinetic vs. thermodynamic control in hydrozirconation reactions. Pure Appl. Chem. 1998, 70, 1077-1082. 

Fig.2. Free energy diagram showing kinetic vs. thermodynamic selectivity...

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