Hydroxypyridine, and

Compare energies of 2-hydroxypyridine and 2-pyridone to see which tautomer is preferred. Use equation (1) to calculate the equilibrium concentrations of the two at room temperature. 

Repeat your analysis for tautomeric equilibria between 4-hydroxypyridine and 4-pyridone, 2-hydroxypyrimidine and 2-pyrimidone and 4-hydroxypyrimidine and 4-pyrimidone. For each, identify the favored (lower-energy) tautomer, and then use equation (1) to calculate the ratio of tautomers present at equilibrium. Point out any major differences among the four systems and rationalize what you observe. (Hint Compare dipole moments and electrostatic potential maps of the two pyridones and the two pyrimidones. How are these related to molecular stability )... 

Pharmacology, chemistry, and technology of medicines on the basis of synthetic antioxidants, derivatives of 3-hydroxypyridine and 5-hydroxynicotinic acid 98MI59. 

Hydroxy-2-methyl-4//-pyrido[l,2-n]pyrimidin-4-one was prepared in the reaction of 2-amino-3-benzyloxypyridine and ethyl acetoacetate at 60 °C, then at 100 °C for 3 h in 22% yield (96MIP1). Reaction of 2-amino-3-hydroxypyridine and ethyl 2-methylacetoacetate in a 1 2 mixture of... 

Reaction of 2-amino-3-hydroxypyridine and cyclohexanone 433 in boiling AcOH yielded N, 1 -diphenyl-6-hydroxy-3-methyl-11 -0x0-1,2-dihydro-11 //-pyrido[2,l-Z)]quinazoline-2-carboxamide (434) (98MI2, 99USP5908840, 99USP5914327). 

Hall, R. J., N. A. Burton, I. H. Hiller, and P. E. Young. 1994. Tautomeric equilibria in 2-hydroxypyridine and in cytosine. An assessment of density functional methods, including gradient corrections. Chem. Phys. Lett. 220,129. 

New conditions (aprotic solvents and highly active bifunctional catalysts 2-hydroxypyridine and DBU/molecular sieves) were found, that allowed a 70% yield of 44 to be obtained in a single step (Scheme 16).39... 

The reaction of 5-amino-2-hydroxypyridine and EMME refluxing diphenyl ether for 1 hr gave 4,6-dihydroxy-1,5-naphthyridine-3-carboxylate in 20% yield after vacuum sublimation of the crude product (71JOC1331). 

TABLE 13. Apparent stability constants of molecular complexes between 2-hydroxypyridine and some aromatic nitro derivatives in hen/enevA at 25 °C125. Reproduced by permission of societa chimica Italiana from Reference 125... 

The presence of substituents on the pyridine ring, which reduce the basicity of the annular nitrogen atom, not only shifts the pyridone-hydroxypyridine equilibrium towards the hydroxy form [62], but they also inhibit A-alkylation. Thus, for example, 3,5,6-trichloro-2-hydroxypyridine is alkylated preferentially on the oxygen atom. Predictably, alkylation of 3-hydroxypyridine and of 2-amino-3-hydroxypyridine leads to the 3-alkoxypyridines in high yield under basic conditions [63] (see Chapter 3). 

Similar studies have recently been extended to aminopyridones and thiones and to aminopyrimidones (Barlin jmd Pfleiderer, 1971 Barlin, 1972). Protonation of 3- and 5-amino-2-hydroxypyridine and 3,4-diamino-2-hydroxypyridine occurs first at the 3- (or 5-) amino-group, but 4- and 6-amino-2-hydroxypyridine and 2- and 3-amino-4-hydroxypyridine first protonate at the oxygen atom, because the amino-group is involved in conjugation with the partially positively charged ring nitrogen. Similar results are found for the amino-pyridine-2(and 4)-thiones (Barlin, 1972). 

Application of pulsed ion gas-phase cyclotron resonance (ICR) spectroscopy to proton affinities of the derivatives 2-methoxypyridine and N- methylpyridin-2-one confirm previous deductions on the enthalpy of 2-hydroxypyridine-pyridin-2-one tautomerism (76JA6048), provided that the difference between the influences of O-methylation on 2-hydroxypyridine and A-me thy lat ion in pyridin-2-one are taken into account. These measurements have been further clarified and extended to other gas phase basicity measurements (79JA1361). A similar estimation of the gas phase basicities of 2- and 4-pyridinethiols and 2- and 4-pyridinethiones confirms that the thiol form is predominant in the gas phase (77TL1777), in line with previous studies involving mass spectrometric deuterium isotope studies (75BSB465). Photoelectron spectroscopy has also been employed in such studies (see Section 2.04.3.6 and Figure 21 for details) <77JCS(P2)1652>. 

Hydroxypyridine and pyridin-2-one are sufficiently reactive to undergo Elbs oxidation, and in both cases the substituent directs hydroxylation mainly para (Scheme 40) (58JA3717). Quinoline may be converted into 3-hydroxyquinoline (6% yield) by Udenfriend oxidation (ascorbic acid and oxygen in the presence of iron(II)) which is believed to involve attack by OH+ rather than radicals (54JBC(208)74i). 

The palladium/copper-catalyzed coupling reaction of 2-iodo-3-methoxy-6-methylpyridine and terminal alkynes leads to the formation of o-methoxyalkynylpyridines which undergo electrophilic cyclization reactions to afford furo[3,2-3]pyridines in moderate yields <2005JOC10292>. A similar Pd/Cu-catalyzed reaction with hydroxypyridines and trimethylsilyl (TMS)-acetylene leads to the formation of alkynyl pyridines which cyclize to form furo[2,3- ]-pyridines in good yields <1998JME1357>. 

Scope of this synthetic strategy is not limited to benzofiirans. The reaction of 2-iodo-3-hydroxypyridine and 1,1 -diethoxy-2-propync under Sonogashira coupling conditions (palladium-copper catalyst system) leads to the formation of the substituted furo[3,2-6]pyridine shown in 3.56.72... 

A number of salts of the pyridinium-3-olates (86) have been prepared from 3-hydroxypyridine and alkyl halides. Whether the products are... 

Hydroxypyridine and formaldehyde give 2-hydroxymethyl-3-hydroxypyridine. Pyrones can be chloromethylated, e.g. (128) — (129). Hydroxymethylation of the 5-position is possible in pyrimidines with at least two electron-releasing substituents. Under Vilsmeier-Haack conditions pyrimidones are converted into 5-formylchloropyrimidines for example (130) gives (131). 

It has been shown that, when 5-amino-5-deoxy-D-xylopyranose (37) is exposed to an acidic medium, it gives rise to 3-hydroxypyridine and to an optically active compound which, it was proposed, might be 1-amino-1,5-anhydro-1 - deoxy-D-flireo-pentuIose (38) Structure (38) has been con-... 

When the blocking group is other than a halogen atom or a keto group, only tars are formed. 8-Hydroxy- 1,7-naphthyridine61 is obtained from 3-amino-2-hydroxypyridine, and 1,5-naphthyridine is obtained from the 2-halo-3-aminopyridines when they are subjected to the Skraup reaction. 3-Aminopyridine 1-oxide aifords the parent 1,5-naphthyridine,62 and both 3-amino-6-hydroxypyridine and 3-amino-6-chloropyridine give 2-hydroxy-l,5-naphthyridine.63 Hart64 has applied the Skraup synthesis to 3-amino-4-hydroxypyridine and has obtained the expected 4-hydroxy-l,5-naphthyridine. 

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