Thermodynamic control carbonyl derivatives

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). 

Carbonyl derivatives and olefins are reduced by electrochemically produced solvated electrons. Camphor and 4-/-butylcyclohxanone thus form the corresponding alcohols in HMPA-ethanol the proportion of epimeric alcohols would suggest that the reduction is thermodynamically controlled [316]. Surprisingly enough, sterically hindered alkenes are reduced at a rate only slightly lower than that of cyclohexene [311]. 

The maximum rates of the reactions of most aldehydes and ketones with semi-carbazide occur in the pH range of 4.5-5.0. For the purpose of making derivatives of carbonyl compounds (Sec. 25.7), semicarbazide is best used in an acetate buffer (CH3CO2H/CH3CO2 ) solution, which maintains a pH in the maximum rate range of 4.5-5.0. However, to demonstrate the principle of kinetic and thermodynamic control of reactions, buffers that maintain higher pHs, and thus produce lower rates, are more desirable. Parts A-C of the experimental procedure involve a phosphate buffer system, whereas the bicarbonate system is used in Part D. It is then possible to compare how the difference in rates in the two buffer systems affects the product ratio. Analysis of the products from the various parts of these experiments provides strong clues as to which of the semicarbazones is the product of kinetic control and which is the product of thermodynamic control. 

Temperature control of the chain walking has been applied with moderate success for synthesis of esters derived from thermodynamic i -allyls or kinetic a-1/ -enyl palladium intermediates by carbonylation in methanol [86]. Some results are shown in Table 6.8. 

By the addition of a phosphine to an alkylcobalt tetracarbonyl, the phosphine-substituted acylcobalt carbonyl can be prepared (182,183). In the case of (methoxycarbonyl)methylcobalt tetracarbonyl as a model compound, some details of the reaction have been revealed. Adding a phosphine to this complex, the kinetically controlled formation of a phosphine-substituted acylcobalt carbonyl is observed that can be converted to the thermodynamically more stable phosphine -substituted derivative. 

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