6-Methyl-2-hydroxypyridine

Abbreviations used pop, dianion of pyrophosphite (P20,.iH2 ) pep, dianion of /u.-methylenebis(phosphite) im, anion of imidazole 4-mpyt, anion of 4-methylpyridine-2-thioI pyt, anion of pyridine-2-thiol pyms, anion of pyrimidine-2-thione bttz, anion of l,3-benzothiazole-2-thiol form, anion of di-p-tolylformamidine dpb, N,W -diphenylben-zamidine mhp, anion of 6-methyl-2-hydroxypyridine chp, 6-chloro-2-hydroxypyridine and dpt, 1,3-diphenyltriazen. 

The reaction of [Mo2(NMe2j6] and l,2-[Mo2Me2(NMe2)4] with the precursors of several bridging ligands, viz. 6-methyl-2-hydroxypyridine (Hmhp), lithium 2,6-dimethylpyridine (Lidmp) and ditolyltriazine (Hdtz), have been described and toe compounds isolated include ... 

Mo2(LL)4 Solv. 4 LL = mhp (6-methyl-2-hydroxypyridine) dmhp (2,4-dimethyl-6-hydroxypyridine) map (2-amino-6-,methylpyridin) PyNHC(0)CH3 (iV- 30, 34... 

NMR study of complexes [M(COD)(/i-L)]2 (M = Rh, Ir L = substituted hydroxypyridinate) has been carried out. Two fluxional processes interconvert nonequivalent COD protons in [Rh(COD)(2-hydroxypyridinate)], but only the lower-energy process is observed in [Ir(COD)(6-methyl-2-hydroxypyridinate)]. The latter process involves only motion of the bridging ligands while the higher-energy process may involve rotation of the coordinated diene or inversion of the eight-membered metallocyclic ring. 

Table 11 summarizes the main results on the tautomerism of mono-hydroxy-, -mercapto-, -amino- and -methyl-azines and their benzo derivatives, in water. At first sight the equilibrium between 2-hydroxypyridine (71) and pyridin-2-one (72) is one between a benzenoid and a non-benzenoid molecule respectively (71a 72a). However, the pyridinone evidently... 

Bis(6-methyl-3-hydroxypyridine) hydrogen bonding, 2, 112 Bismin, 1,4-dihydro-properties, 1, 553 Bisminane, 1-ethyl-properties, 1, 550 Bisminanes, 1, 550 Bismins... 

Recently, many investigators have extended the early observations that the ultraviolet spectra of - and y-hydroxypyridines resemble those of their A -methyl (not the 0-methyl) derivatives. This spectral resemblance is found both in aqueous solutions and in solutions of solvents with low dielectric constants, e.g., quinol-4-one in benzene, indicating that these compounds exist predominantly in the oxo form under all conditions. These data are summarized in Table I. In contrast, 4-hydroxyquinoline-3-carboxylic acid has been tentatively concluded to exist in the hydroxy form %- pjTid-2-one-4-carboxylic acid has also been formulated as a hydroxy compound, but this has been disputed. ... 

Many of the properties oj -hydroxypyridines are typical of phenols. It was long assumed that they existed exclusively in the hydroxy form, and early physical measurements seemed to confirm this. For example, the ultraviolet spectrum of a methanolic solution of 3-hydroxypyridine is very similar to that of the 3-methoxy analog, and the value of the dipole moment of 3-hydroxypyridine obtained in dioxane indicates little, if any, zwitterion formation. However, it has now become clear that the hydroxy form is greatly predominant only in solvents of low dielectric constant. Comparison of the pK values of 3-hydroxypyridine with those of the alternative methylated forms indicated that the two tautomeric forms are of comparable stability in aqueous solution (Table II), and this was confirmed using ultraviolet spectroscopy. The ratios calculated from the ultraviolet spectral data are in good agreement with those de-... 

The pKa values of 4-hydroxypyridine 1-oxide (51 52) and the methylated derivatives of both tautomeric forms indicate that the parent compound exists as a mixture containing comparable amounts of both forms in aqueous solution. Nuclear magnetic resonance spectra support this conclusion, but the ultraviolet spectra of the tautomeric compound and both alkylated derivatives are too similar to give information concerning the structural nature of the former. ... 

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). 

Hydroxypyridine (86, R = H) and its derivatives also belong to the class of heterocyclic enols. In benzene and dioxane, 3-hydroxy-pyridine occurs as the neutral molecule (and not as a betaine).Its reaction with diazomethane, in heterogeneous media, gives a mixture of 3-methoxypyridine (86, R = Me) (10%) and l-methyl-3-hydroxy-pyridinium betaine (87) (30%If tert-butanol is used as a... 

Hydroxypyridine Dimethyl carbamic acid chloride Methyl bromide... 

Reductive decarbonylation and decarboxylation can be carried out by (TMSlsSiH using acyl chlorides, phenylseleno esters, or N-hydroxypyridine-2-thione esters. Examples are shown in Reactions (17)-(19). Hydrolysis of the methyl ester followed by decarbonylation at the C2 position of hexahydropyrro-loindole (+)-17 afforded the desired tricycle (+)-18 in 84% yield and >99% ee. ... 

The dioxygenase that brings abont the degradation of 2-methyl-3-hydroxypyridine-5-car-boxylate to a-(A-acetylaminomethylene)snccinic acid (Sparrow et al. 1969). 

Ochiai and Ito reported that the reaction of ethyl acetoacetate and diethyl aminomethylenemalonate (13) in the presence of hydrogen chloride gave 4-hydroxypyridine-3-carboxylate (1314) at room temperature, while in the presence of sodium in boiling benzene, the product was 2-methyl-4-hydroxypyridine-3,5-dicarboxylate (1315) (41CB1111). Aqui et al. proved... 

Grabowska et al [112] reported methylation of 2-hydroxypyridine with methanol over hydrothermally synthesized zinc aluminate spinels. N-methyl-2-pyridone was formed selectively (95%) and 100% 2-hydroxy pyridine conversion was achieved at 340°C. During the experiment the activity of the catalyst was shown to be stable and catalyst can be regenerated repeatedly without any significant loss of activity by passing air through the catalyst bed at 500°C. 

Table 11 summarizes the main results on the tautomerism of mono-hydroxy-, -mercapto-, -amino- and -methyl-azines and their benzo derivatives, in water. At first sight the equilibrium between 2-hydroxypyridine (71) and pyridin-2-one (72) is one between a benzenoid and a non-benzenoid molecule respectively (71a 72a). However, the pyridinone evidently has a continuous cyclic p- orbital system, containing six it- electrons, the usual aromatic count, if the carbonyl group contributes none. This assumption implies the formula (72b), from which by redistribution of electrons we arrive at (72c), which has the same benzenoid system as (71a). Further canonical forms (71b, 71c) can be drawn of (71) which correspond to the non-benzenoid forms of (72). The elusive property of aromaticity is therefore possessed by both tautomers, although not necessarily by both equally. When the carbonyl oxygen of (72) is replaced by less electronegative atoms, as in the imine tautomers of amino heterocycles, or the methylene tautomers of methyl derivatives, the tendency towards polarization in forms corresponding to (72b) and (72c) is considerably less, and the amino and methyl tautomers are therefore favoured in most instances. 

The PE spectra of hydroxy- and mercapto-pyridines have been examined, together with the model iV-alkyl and S- or O-alkyl compounds, to elucidate the tautomeric equilibria in the vapor phase (77JCS(P2)1652) (Section 2.04.4.2). Figure 21 and Table 13 show details of the PE spectra of l-methylpyridin-2-one, 2-methoxypyridine and the tautomeric mixture at equilibrium of pyridin-2-one and 2-hydroxypyridine. This indicates that there is approximately 25% of oxo form present once adjustment has been made for the expected influence of methylation, similar measurements reveal ca. 10% of the thione form in the mercapto-thione equilibrium. Other spectra indicate that 3- and 4-hydroxy- and 3- and 4-mercapto-pyridine exist in the vapor phase with less than 5% of the alternative tautomer present. 

Beak has measured the UV spectra of 2- (0.4) and 4-hydroxypyridine (<0.1), 6-chloro-2-hydroxypyridine (0.05), 2- (<0.1) and 4-mercaptopyridine (<0.1) and acridin-5-one (>10) (73JA1700, 76JA171). A heated cell was employed with vacuum jacketed windows, over the temperature range 120-140 °C. It was thus demonstrated that these compounds exist predominantly in the form named above (the figure in brackets after each name gives the value of Kt = [NH]/[OH], or [NH]/[SH]), using the methylated compounds as model chromophores. 

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>. 

Treatment of the iV-methylated product (115) of 3-hydroxypyridine with an ion exchange resin generates the betaine (116 Scheme 97) (71JCS(C)874). Reduction of 1-substituted 3-oxidopyridinium betaines with sodium borohydride gives hexahydro derivatives in good yields <8lH(l6)l883). 

Methylation of the TV-oxides of 2- or 4-hydroxypyridine in basic medium gives the TV-methoxypyridone (57JCS4375) whereas diazomethane with the 4-isomer gives both C—OMe and N—OMe products. 

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