Substitution thermodynamics

For complexes like PtL2X2 (X = halogen L = NH3, PR3, etc.) where cis-and trans-isomers exist, the trans-isomer is usually thermodynamically more stable. The c/s-isomer may be formed first in a reaction and, in the case of platinum, may be relatively inert to substitution. (Thermodynamic data are relatively scarce trans-Pt(NH3)2Cl2 is some 13kJmol-1 more stable than the cis-isomer.)... 

Reaction of the unsymmetrical substituted acetylene Me3SiC=CPy with 1 yields, after substitution of the alkyne, the kinetically favored unsymmetrical substituted complex 55a as well as the symmetrically substituted, thermodynamically more stable product 55b [38]. 

If we imagine that both defects A and B and associate defect (AB) are distributed in conditions of complete configurational disorder, and if we substitute thermodynamic activity for the molar concentration, we have... 

Regioselectivity in the LiTMP metalation of 2,4-dichloropyrimidine (109) was shown to be dependent on temperature and solvent (Scheme 33) (91JHC). In THF/Et20 at - 100°C, metalation followed by acetaldehyde quench gave the 5-substituted (kinetic) product 110, whereas in THF/ HMPA mixture at -70°C, treatment with the same electrophile afforded the corresponding 6-substituted (thermodynamic) derivative 111. Minimum neglect of differential overlap (MNDO) calculations support the observed results. 

Treatment of 2-methylcyclohexanone with NaOCH2CH3 in CH3CH2OH solution at room temperature forms the more substituted thermodynamic enolate, which then reacts with CH3I to form B. 

It can eliminate a vicinal proton to form an alkene. If more than one vicinal proton is available, the most highly alkyl-substituted (thermodynamically most stable) alkene is formed. 

What does all of this mean The reaction of 2-pentanone with LDA in THF at -78°C constitutes typical kinetic control conditions. Therefore, formation of the kinetic enolate and subsequent reaction with benzaldehyde to give 34 is predictable based on the kinetic versus thermodynamic control arguments. In various experiments, the reaction with an unsymmetrical ketone under what are termed thermodynamic conditions leads to products derived from the more substituted (thermodynamic) enolate anion. Thermodynamic control conditions typically use a base such as sodium methoxide or sodium amide in an alcohol solvent at reflux. The yields of this reaction are not always good, as when 2-butanone (37) reacts with NaOEt in ethanol for 1 day. Self-condensation at the more substituted carbon occurs to give the dehydrated aldol product 38 in 14% yield. Note that the second step uses aqueous acid and, under these conditions, elimination of water occurs. 

The substitute thermodynamic path (19) is denoted as O, expressing the irreversible cycle itself. For this path to be closed, the heat AQ g must be drained off from the medium C when its temperature is Tq. This heat is greater than the heat AQo when only the reversible cycle O is considered. Thus we have... 

Under the conditions used for the generation of silyl enol ethers of symmetrical ketones, unsymmetrical ketones give mixtures of structurally isomeric enol ethers, with the predominant product being the more substituted enol ether (eq 20). Highly hindered bases, such as lithium diisopropylamide (LDA), favor formation of the kinetic, less substituted silyl enol ether, whereas bro-momagnesium diisopropylamide (BMDA) generates the more substituted, thermodynamic silyl enol ether. A comhination of TMSCl/sodium iodide has also been used to form silyl enol ethers of simple aldehydes and ketones as well as from a,p-unsaturated aldehydes and ketones. Additionally, treatment of a-halo ketones with zinc, TMSCl, and TMEDA in ether provides... 

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