Selective syntheses using cyclodextrins as catalysts part 5. para-Selective hydroxymethylation of phenol by formaldehyde using hydroxypropyl cyclodextrins

Abstract

4-(Hydroxymethyl)phenol (1) has been selectively synthesized from phenol and formaldehyde by use of hydroxypropyl cyclodextrins (HP-CyDs) as catalysts. In the presence of 0.6 mol dm^–3(M) of HP-β-CyD (degree of substitution 5.8) at 4 °C, the rate constant (k₁) for the formation of (1) is 16 times as large as that (k₂) for the formation of 2-(hydroxymethyl)phenol (2) as by-product. In its absence, however, the k₁/k₂ ratio is only 2.1. Significantly, the selectivity-enhancing effects of the HP-CyDs are much larger than those of CyDs without the chemical modification: the k₁/k₂ ratios in the presence of 0.3M of α-, β-, and γ-CyDs are only 2.5, 2.9, and 1.9. Kinetic analyses indicate that the hydroxypropyl residues increase the selectivity by the interaction with the formaldehyde accommodated in the cavity of the HP-CyD.