4- Hydroxybenzoic acid, cyclodextrin

Fig. 3. GROESY spectra of the 1 1 inclusion complex of 4-hydroxybenzoic acid and /3-cyclodextrin (/3-CD), saturated solution in D2O. (a) Normal spectrum (b) and (c) GROESY spectra obtained after pulsing selectively the guest aromatic protons H-2 Ha and H-3 (Hb), respectively. The inner H-3 and H-5 protons of /3-CD are assigned on the traces. All spectra were acquired in about 40 min., using 1024 scans, with the settings described in...

Uekama, K., Ikeda, Y., Hirayama, F., Otagiri, M., and Shibata, M. 1980. Inclusion complexation of p-hydroxybenzoic acid esters with andfS-cyclodextrins dissolution behaviors and antimicrobial activities.Yakugaku Zasshi, 100 994-1003. 

Cyclodextrin Organic molecule Hydrophobic/ van der Waals Cavitate (ct-cyclodextrin) (p-hydroxybenzoic acid)... 

The p-cyclodextrin-catalyzed reaction of phenols and carbon tetrachloride in an alkaline medium in the presence of copper powder also results in almost exclusive attack at the para-position to give 4-hydroxybenzoic acids. 2-Methylphenol also undergoes almost exclusive para-carboxylation. P-Cyclodextrin has only a negligible effect on the carbox-ylation of 3-methylphenol.-... 

Lehner SJ, Muller BW, Seydel JK. Interactions between p-hydroxybenzoic acid esters and hydroxypropyl-P-cyclodextrin and their antimicrobial effect against Candida albicans. Int J Pharm 1993 93 201-208. 

Phenolic compounds form inclusion complexes with a-cyclodextrin (85), enhancing the fluorescent properties of the aromatic analytes. For example, p-hydroxybenzoic acid (86a),... 

SELECTIVE SYNTHESIS OF 4-HYDROXYBENZOIC ACID USING IMMOBILIZED CYCLODEXTRIN... 

Previously (10,13), the authors succeeded in selective syntheses of 4-hydroxybenzoic acids from phenols and carbon tetrachloride, using 3-cyclodextrin (3-CyD) as catalyst. With the use of 3-CyD catalyst, a side reaction, carboxylation at the ortho-position, was largely suppressed, and 4-hydroxybenzoic acids were synthesized in selectivity larger than 95 %. In addition, various aromatic substitution and addition reactions were achieved in virtually 100 % selectivity and high yields in the presence of CyDs as catalyst (9-13). Selective catalyses involve regioselectivity, regulation of molecular sizes of intermediates and products, and/or protection of unstable products (9-13). 

Salicylic acid, three impurities (4-hydroxybenzoic acid, phenol, 4-hydroxy-isophthalic acid), and two metabolites (gentisic acid, salicylglycine) were baseline resolved in 12min on a phenyl column (A = 235 nm) using a mobile phase of 40/60/1 methanol/water/H3P04 with 2.5 g -cyclodextrin/L to pH 2 [564]. The author notes that a C g column was ineffective. Linear ranges of 0.1-100 pg/mL and detection limits of 0.1 pg/mL (S/N = 3) were reported. 

High resolution carbon-13 NMR spectroscopy is one of the most useful methods in the analysis of the structure and molecular dynamics of cyclodextrin inelusion-complexes both in aqueous solution[1,2] and in the solid state[3]. Earlier cariDon-13 NMR studies of a-CD inclusion complexes with benzoic acid, p-nitrophenol, and p-nitrophenolate in aqueous solution have shown that the included lead(head see Fig.lA) carbons show high-field shifts compared to low-field shifts of corresponding para(tail Fig.lA) carbons[4,5]. Similar distinctive patterns of carbon-13 displacement s have been also observed for p-hydroxybenzoic acid and it has been concluded that the carboxyl group of p-hydroxybenzoic acid is directed into the a-CD cavity [4]. A variety of substituted benzenes are known to show quite similar carbon-13 high (head) and low (tail) field shifts, irrespective of the kinds of substituents if their size are matched to the a-CD cavity [4,5]. These characteristic carbon-13 displacements induced by complexation with a-CD... 

In their initial communication [37], they used CNDO/2 calculations to calculate the dipole moment of a-cyclodextrin when it was complexed with p-nitrophenol, benzoic acid, and p-hydroxybenzoic acid. In the case of complexation with p-nitrophenol, the a-cyclodextrin molecule was found to have an unusually large dipole moment of 13.5 D, which is directed from the side of the secondary hydroxyls (broad rim) to that of the primary hydroxyls (narrow rim). Due to slight distortions of the individual glucose units, the axis of the dipole deviated about 30 from the axis of the cyclodextrin cup. The dipole moment of the p-nitrophenol guest was found to be 5.0 D in the direction of the hydroxyl group, and antiparallel to the dipole moment of the cyclodextrin (Figure 7). 

Harata K (1997) The structure of the cyclodextrin complex. V. Crystal structures of a-cyclodextiin complexes with p-nitrophenol and p-hydroxybenzoic acid. Bull Chem Soc Jpn 50 1416-1424... 

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