Pyridine association with methanol

Figure 17. (a) Mass spectra of products arising from reactions of TisCu with methanol. The number stands for the number of methanols associating onto TiaOn, note that association reactions terminate at the eighth step, (b) Under similar conditions, the clustering of pyridine truncates at n = 4. (a) Taken with permission from ref. 115 (b) Taken with permission from NATO ASI Series on Laige Clusters of Atoms and Molecules Kluwer Academic Dordrecht, 1996, pp 371-404. 

More recently, the use of the chloroformate-aqueous alkali method has been revived by G. R. Barker and his associates in order to prepare a suitably protected D-ribose carbonate for a synthesis of a-D-ribofuranosyl phosphate. (An analogous synthesis of the latter compoimd, involving a phosgene-pyridine reaction, appeared almost simultaneously. ) Condensation of D-ribose with methyl chloroformate in the presence of aqueous sodium hydroxide led to the formation of a mixture of the anomers of l,5-di-0-(methoxycarbonyl)-D-ribofuranose 2,3-carbonate (LII), which was resolved by fractional recrystallization. The treatment of either of the derived D-ribofuranosyl chlorides with methanol and silver carbonate... 

The association constant of pyridazine with ethanol was found to be 4.9 (from electronic absorption spectra) and 6.8 (infrared absorption spectra), and the corresponding values for the strength of the hydrogen bond are 4.2 and 4.6 kcal. The hydrogen-bonded form of P3n-idazine was considered to comprise one alcohol at one azine-nitrogen at small mole ratios of alcohol to azine and to involve the second nitrogen at high mole ratios (an additional shift in the electronic spectrum. The association constants (3.1-3.8) of pyridine, quinoline, and isoquinoline with methanol in carbon tetrachloride have been determined by infrared spectroscopy. 

For over 60 years, the specific titration of water has used a reagent developed by Karl Fisher, which consists of iodine, sulfur dioxide, and pyridine in methanol. The Karl Fisher titration of water is addressed in most analytical chemistry texts and is not presented here. A brief review with a pharmaceutical perspective has recently been published. However, the advantages and disadvantages of this method for the characterization of water associated with solids are discussed later. 

The well-known powerful basic catalyst 4-dimethylaminopyridine has been the inspiration for a new transesterification catalyst for a-hydroxy esters (5). The designer compound is 2-formyl-4-pyrrolidinopyridine (6). By the introduction of an aldehyde group into the pyridine ring at the 2-position, the ready formation from (5) of a hemi-acetal (7) makes possible, via a covalent pre-association step, a facile displacement by pyridine nitrogen of the aryloxy group of the a-hydroxy ester (5). The product of this process, a tricyclic pyridinium compound (9), is formed by a nucleophilic mechanism (Scheme 1, pathway b), and interaction with methanol then leads to the methyl ester of the a-hydroxy acid (10) and regeneration of the catalyst. However, a study of the mechanism of this catalytic process discounted the nucleophilic mechanism and provided clear evidence instead for a general base mechanism, which proceeds via a dioxolanone (8) (Scheme 1, pathway a) ... 

Dihydro-4-methylcyclopent[b]indol-l(2H)-one (1.7 g) and hydroxylamine hydrochloride (1.925 g) in pyridine were heated at 60°C for 18 h and cooled. The reaction mixture was evaporated in vacuo to a residue to which was added 8% sodium bicarbonate (150 ml). Extraction with ethyl acetate (300 ml) produced a suspension in the organic layer this layer and associated solid was separated from the aqueous layer. The aqueous layer was re-extracted with ethyl acetate (250 ml). The combined organic extracts (and suspended solid) were evaporated to a residue, boiled with a mixture of ethanol (150 ml) and methanol (150 ml) and cooled to 50°C. The residue was adsorbed from this solution on to FCC silica and applied to an FCC column. Elution with ethyl acetate/3-10% methanol provided the title compound (1.69 g), m.p. 219-224°C (decomp.). 

Waksmundzki et al. extensively examined the surface areas and microporosities of imprinted silica surfaces [44]. It was found that although the template itself had little effect on the total surface area, the sizes of the micropores were positively correlated to the size of the template. Subsequent studies on the sorption of template to silicas imprinted with pyridine [45-50], quinoline and acridine [45-47], and 2-picoline, 2,4-lutidine and 2,4,6-collidine [50], combined with thermodynamic studies on the heat of wetting of template or methanol/water sorption [47,51-53], led to the conclusion that these templates were adsorbed as multilayers to the silica. This observation supported the association mechanism hypothesis. The possibility of a footprint mechanism and an association mechanism coexisting in a concentration dependent fashion does not appear to have been considered. 

Another asymmetric sulfoxidation reported by Fujita et al. [102] used a chiral binuclear titanium(IV) complex (4 mol% equiv) in methanol with trityl hydroperoxide at 0°C, which gave methyl phenyl sulfoxide with an ee of 53% and a good yield (87%). The complex was prepared by treating TiC in pyridine with -disalicylidene-(f ,/ )-l,2-cyclohexanediamine. The structure of the catalyst was determined by x-ray analysis. A binuclear titanium (IV) complex was present with an oxygen bridge between the two titanium atoms (Ti—O— Ti unit). This oxygen apparently comes from atmospheric or solvent moisture. Each titanium atom is octahedrally coordinated, and the planes of each titanium atom with its associated Schiff bases are almost parallel to each other. 

Prompted by earlier results which indicated that the rate law for substitution of Cl in square-planar rran -[Pt(PEt3)2(R)Cl] (R = phenyl, jp-tolyl, or mesityl) complexes included an associative as well as the normal dissociative path only in the case of substitution by strong biphilic ligands (e.g. CN, SeCN ), Ricevuto et al. have re-examined the reaction with weakly nucleophilic pyridine in methanol ... 

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