Pyridine xanthine derivatives

Dimerizations of p-Rich N-Heteroaromatic Compounds and Xanthine Derivatives. Sekine, Toshikazu Higuchi, Yoshihiro Yamada, Tomoko Murakoshi, Isamu (Fac. Pharm. Sci., Chiba Univ., Chiba, Japan 260). Chem. Pharm. BuU. 1989, 37 (8) 1987-9 (Eng.). N-Methylimidazole, benzimidazole, and N-methylbenzimidazole condensed dehydrogenatively to afford the corresponding sym. dimers when heated in the presence of Pd-Pt/C catalyst and pyridine N-oxide. Imidazole, pyrazole, and N-methylpyrazole did not dimerize under the same conditions. The same reactions using caffeine and 1,7-dimethylhypoxanthine gave the eorresponding dimers. 

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

This enzyme [EC 1.2.3.1] catalyzes the reaction of an aldehyde with water and dioxygen to produce a carboxylic acid and hydrogen peroxide. The enzyme uses both heme and molybdenum as cofactors. In addition, the enzyme can also catalyze the oxidation of quinoline and pyridine derivatives. In some systems this enzyme may be identical with xanthine oxidase. 

The pyridinium ylide (24) is obtained from the reaction of 8-bromotheophylline with pyridine. Alkylsulphonate salts of caffeine have been synthesized. A new purine-into-pteridine ring transformation has been discovered. For example, the quaternary salt (25) was obtained by direct alkylation of an appropriate xanthine with ethyl bromoacetate. Base-catalysed hydrolysis of (25) gave the pyrimidine (26), which could be cyclized to give the isoxanthopterin derivative (27). 

Also values of alcohols(22,31,33), ethers(11b,34,35a), amines(34, 35b), ketones(11b,36), amides(11b,32,36,37a,b), pyridines and others heterocyclic compounds containing nitrogen(38), phenols (22,39), benzene and derivatives(llc,22b,40), esters(llb), polyethers (28,41), polyamines(35b,41), polyols(42-44), polycarboxylic acids (43), aminoalcohols(41), aminoethers(31,35b,41), hydroxyethers(11a, 28), xanthines(45), ureas(46) have been preferably obtained from direct measurements of the heat capacity of the solutions, but in some cases also by differentiation of the heats of solution with respect to temperature(22a,b,28,43,45) or as second derivatives with respect to temperature of solubility data(33,47). 

Silver salts have been used extensively as oxidants in many different types of biaryl CDC reactions, such as the arylation of indoles, " " azoles, thiophenes," " chromones, xanthines," uracils," and pyridine-iV-oxides." " " They are also used in the inter- and intramolecular coupling of simple arenes. ° Recently, Zhang and co-workers oxidatively coupled thiophene derivatives and fluorinated arenes, using only 2.5 mol% of Pd(OAc)2 as a catalyst and AgCOs as an oxidant (Scheme 6.8)." " ... 

The You group used a [Pd(l,l -bis(diphenylphosphino)ferrocene (dppf))Cl2] catalyst and a Cu(OAc)2 H2O oxidant system. They also added a catalytic amount of the 2-dicyclohe) lphosphino-2, 4, 6 -triisopropylbiphenyl (XPhos) ligand, to prevent decomposition of the indole derivatives, and a CuCl additive, that further helped control the regioselectivity. The reaction conditions were found to couple a wide array of heterocycles including, xanthines, pyridine-iV-oxides, azoles, indoles and pyrroles in good-to-excellent yields. 

Figure 4.42 Methyl xanthines are derivatives of pyrroie and pyridine.

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