Hydroxyaldehyde-hemiacetal equilibria

Hydroxyaldehyde Hemiacetal Ring size % Hemiacetal at equilibrium... 

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... 

All y- and <5-hydroxyaldehydes and -hydroxyketones are in equilibrium with their cyclic hemiacetals, the position of equilibrium depending on... 

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. 

Although the cyclic hemiacetal (also called lactol) product Is more stable, it is still in equilibrium with some of the open-chain hydroxyaldehyde form. Its stability, and how easily it... 

Glucose, of which many of the chemical reactions actually involve the small concentration of acyclic polyhydroxyaldehyde in equilibrium with the cyclic forms, hemiacetals containing a tetrahydropyran this illustrates the inherent stability of chair conformers of saturated six-membered systems. The propensity for cyclisation is a general one 5-hydroxyaldehydes, -ketones and -acids all easily form six-membered oxygen-containing rings — lactols and lactones respectively. 

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