Equilibrium constants hemiacetal

The equilibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals or hemiketals show the same response to structural features as the hydration reaction. Equilibrium constants for addition of metiianoHb acetaldehyde in both water and chloroform solution are near 0.8 A/ . The comparable value for addition of water is about 0.02 The overall equilibrium constant for formation of the dimethyl acetal of... 

The position of equilibrium, i.e. whether the carbonyl compound or the addition product is favoured, depends on the nature of the reagents. The equilibrium constant is often less than 1, so that the product is not favoured, and many simple hemiacetals and hemiketals are not sufficiently stable to be isolated. However, stable cyclic hemiacetals and hemiketals... 

J.P. Guthrie, Carbonyl addition reactions Factors affecting the hydrate-hemiacetal and hemiacetal-acetal equilibrium constants. Can. J. Chem. 53 (1975) 898-906. 

The much lower thermodynamic stability of hemiorthoesters compared to hemiacetals is illustrated by comparing the equilibrium constant for the formation of [121] from the corresponding hydroxyester, 5 x 10-7 to 1 x 10" 6 (Table 17) with that for the formation of hemiacetal [123] from the corresponding hydroxyaldehyde [122] which is 8.1 in 75 25 dioxan-water... 

Harron et al., 1981). The hemiacetal is therefore relatively more stable than the hemiorthoester by 9-10 kcal mol-1. A similar comparison of the equilibrium constant for the formation of dimethyl hemiorthobenzoate... 

Equilibrium constants for hydration and hemiacetal fonnation have been calculated for representative highly fluorinated ketones.5 Both reactions were substantially more favourable in cyclic than acyclic systems. 

In this example the oxygen of the hydroxy group acts as an intramolecular nucleophile. Recall from Section 8.13 that intramolecular reactions are favored by entropy. Therefore, the formation of a cyclic hemiacetal has a larger equilibrium constant than a comparable intermolecular reaction. This reaction is especially important in the area of carbohydrates (sugars) because sugars contain both carbonyl and hydroxy functional... 

Entropy dominates equilibrium constants in the difference between inter- and intramolecular reactions. In Chapter 6 we explained that hcmiacetal formation is unfavourable because the C=0 double bond is more stable than two C-0 single bonds. This is clearly an enthalpy factor depending simply on bond strength. That entropy also plays a part can be clearly seen in favourable intramolecular hemiacetal formation of hydroxyaldehydes. The total number of carbon atoms in the two systems is the same, the bond strengths are the same and yet the equilibria favour the reagents (MeCHO + EtOH) in the inter- and the product (the cyclic hemiacetal) in the intramolecular case. 

The product is in fact a hemiacetal. Like hydrates, most hemiacetals are unstable with respect to their parent aldehydes and alcohols for example, the equilibrium constant for reaction of acetaldehyde with simple alcohols is about 0.5 as we saw in Chapter 13. 

So by making [MeOH] very large (using it as the solvent, for example) we can turn most of the aldehyde into the hemiacetal. However, if we try and purify the hemiacetal by removing the methanol, more hemiacetal keeps decomposing to maintain the equilibrium constant. That is why we can never isolate such hemiacetals in a pure form. 

This compound can form a cyclic hemiacetal because it has an alcohol nucleophile and an aldehyde electrophile in the same molecule. Although hemiacetals are normally not favored at equilibrium, formation of a six-membered cyclic hemiacetal has a larger equilibrium constant than a comparable intermolecular reaction. In this case the equilibrium favors the cyclic hemiacetal, there is no carbonyl band in the IR spectrum. 

It is obvious that, knowing the equilibrium constant (K), the droptime ( i), and a hypothetical diffusion current (id), it is possible to calculate the rate constant for formation of the depolarizer from the polaro-graphically inactive forms of substances (for example, the formation of non-hydrated glyceraldehyde, or acyclic forms of higher aldoses from their cyclic hemiacetal forms). 

The rate constants, kj, for the opening of the hemiacetal ring were calculated by the authors from equation (9) for equilibrium mixtures of the a and p anomers of some aldopentoses and aldohexoses. Assuming that the thickness (8, in cm) of the reaction layer equals the mean distance between two aldose molecules in solution, k values (k/ = kh S) can be calculated, and, from known values of k , k, and D, values of the equilibrium constant K) can also be found by using equation 12). The results are given in Table I. 

A physical chemistry text such as Physical Chemistry, 9th edn, by Equilibrium constants for hemiacetal formation J. P. Guthrie P. Atkins and J. de Paula, OUP, Oxford, 2011, will give you much Can J. Chem. 1975, 898. 

A. Equilibrium Constants for the Hydration Reaction of Various Carbonyl Compounds B. Association Constants for Hemiacetal Formation in Methanol ... 

We have seen that a compound containing both an OH group and an aldehyde moiety will undergo an intramolecular process to form a cyclic hemiacetal, with a favorable equilibrium constant. A similar equilibrium between open and closed forms is observed for carbohydrates. For example, D-glucose can exist in both open and closed forms. The following Haworth projections indicate the configuration at each chirality center ... 

Reaction is acid catalyzed and proceeds by way of a hemiacetal or hemiketal as an intermediate. Equilibrium constant normally favorable for aldehydes, unfavorable for ketones. Cyclic acetals from vicinal diols form readily. 

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