4- Methoxy-2-pyridone

The 2-nitration of 3-hydroxy- and 3-methoxy-pyridine in 85-96% sulphuric acid involves the conjugate acids, whilst the 3-nitration of 6-hydroxy and 6-methoxy-2-pyridone in 70-77 % sulphuric acid involves the free bases, which react at, or near to the encounter rate. ... 

Although it had been suggested on the basis of Raman and infrared evidence that 2- and 4-pyridone are protonated on nitrogen, subsequent information has established that protonation occurs on oxygen. s - Protonated 6-methoxy-2-pyridone, 6-methoxy-l-methyl-2-pyridone, 6-hy-droxy-l-methyl-2-pyridone, and 2,6-dimethoxypyridine all exist as structure XII.S07. ... 

Hydroxy-2-pyridone (XU-516) and a large excess of diazomethane give 6-methoxy-2-pyridone (2%), 6-methoxy-lmethyl-2-pyridone (4%), 2,6-dimeth-oxypyridine (8%), and the 3-( methylhydrazonc) of l-methyl-2,3,6-pyridine-trione (XD-517) (14%). ° 6-Methoxy-2-pyridone and diazomethane give a mixture of O- and yV-methylation products. 6-Hydroxy- l-methyl-2-pyridone gives 6-methoxy-lmethyl-2-pyridone and XD-517. ° ... 

Metho3 -2-pyrldone, amino-methylation of, 813 6-Methoxy-2-pyridone, 752... 

Nondegenerate double proton migrations between a solute molecule and the molecules of the solvent (water) may determine the mechanism of intermolecular proton transfers that give rise to a new tautomeric form. Thus, using the relaxation method of temperature jump, it was found [97] that the tauto-merization of 6-methoxy-2-pyridone proceeds as a nondissociative concerted process of bifunctional interaction with one molecule of water ... 

The similarity of their rate profiles, and the similarity of their rate constants for nitration at a particular temperature and acidity show that 4-pyridone, i-methyl-4-pyridone, and 4-methoxypyridine are all nitrated as their cations down to about 85 % sulphuric acid. The same is true of 2-methoxy-3-methylpyridine. In contrast, 3- and 5-methyl-2-pyridone, i,5-dimethyl-2-pyridone and 3-nitro-4-pyridone all react... 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

Cyclic hydroxamic acids and V-hydroxyimides are sufficiently acidic to be (9-methylated with diazomethane, although caution is necessary because complex secondary reactions may occur. N-Hydroxyisatin (105) reacted with diazomethane in acetone to give the products of ring expansion and further methylation (131, R = H or CH3). The benzalphthalimidine system (132) could not be methylated satisfactorily with diazomethane, but the V-methoxy compound was readil3 obtained by alkylation with methyl iodide and potassium carbonate in acetone. In the pyridine series, 1-benzyl-oxy and l-allyloxy-2-pyridones were formed by thermal isomeriza-tion of the corresponding 2-alkyloxypyridine V-oxides at 100°. 

Similar reasoning was applied to determination of the reacting form of 1-hy-droxy-2,6-dimethyl-4-pyridone, its rate being compared to that of 4-methoxy-... 

Methoxy-2,6-dimethylpyridine 4-Hydroxy-2,6-diraethylpyridine-l-oxide anion l-Hydroxy-2,6-dimethyl-4-pyridone 4-Methoxy-2,6-dimethylpyridine-l-oxide... 

As a general rule, in the case of CSPs featuring hydrophobic pockets, a decrease of mobile phase flow-rate results in an increase of chromatographic resolution (Rs), as a consequence of better stationary phase mass transfer [78]. This change has significant impact mostly in RP mode [17]. In the NP enantioselective separations of two test solutes (4-hexyl-5-cyano-6-methoxy-3,4-dihydro-2-pyridone and... 

Metalation at the /3-position of 2-pyridones has also been achieved, and thus the lithiation of 4-methoxy-l-methyl-2-pyridone occurred exclusively at the 3-position to give 135 [92JCS(P1)67], whereas halogen-metal exchange on the analogous bromide was used to generate the 5-lithio deriva-... 

Anomalous isomerizations have been noted during the photolytic and thermal rearrangements of 3-acyl-2-methoxy-3//-azepines (2 R -acyl, R2 = OMe) and 3-acyl-3H- azepin-2-ones (69T5217). Irradiation in methanol solution produces mixtures of 3-azabicyclo[4.1.0]hepta-2,4-dienes (28 R1==acyl and H, R2 = OMe, R3 = H) (or -4-ene-2-ones) and 3-phenacylpyridines (or pyridones), albeit in poor yields. Detailed, but tentative, arguments involving azanorcaradiene and/or diradical intermediates are presented to explain the formation of these unusual products. 

Synergism between OMe and 2-oxazolinyl DMGs allows clean C-2 metalation of 2-methoxy-4-oxazolinyl pyridine (395) with MeLi to give, after quench with aryl aldehydes, derivatives 396 (Scheme 122) (87S142). These were further converted into the pyridones 397, which served as intermediates for the preparation of biologically interesting condensed azaaro-matics (see Section VIII). 

Halogen atoms in pyrones and pyridones e.g. 902) are unreactive toward SAE nucleophilic displacement. 3-Halopyridines are less reactive than the a- and 7-isomers but distinctly more reactive than unactivated phenyl halides. Thus, a bromine atom in the 3-position of pyridine or quinoline can be replaced by methoxy (NaOMe-MeOH, 150°C), amino (NH3-H20-CuS04, 160°C) or cyano (CuCN, 165°C). 5-Halogens in pyrimidines are also relatively unreactive. 

Methoxy-2-(l//)-pyridone (12 g, 96 mmol) was dissolved in 280 mL of water containing 3.84 g (96 mmol) of sodium hydroxide. A solution of silver nitrate (16.32 g, 96 mmol) in 64 mL of water was added. The mixture was vigorously stirred at room temperature for 10 min. After filtration, the solid was washed with MeOH and ether, dried in vacuo to give 21 g of silver salt in 94% yield. 

Ring E is closed by lactonization with 60% sulfuric acid and warming to 115 C. Simultaneously, the methoxy group is activated (by protonation) with respect to nucleophilic attack by the pyridone nitrogen. Ring C is closed via an SN reaction to produce the target molecule, (+)-camptothecin (1). 

The 4-pyridones behave similarly, with the neutral tautomer reacting below pH 6 and the anion at higher pH. The observation that 4-methoxy-pyridine shows little comparative reactivity over the whole range is evidence that the hydroxy tautomer is not involved in the bromination process. Again, once the first bromine has entered the ring, further bromination occurs more readily because of easier anion formation (83CJC2556). 

Methyl-l-penten-3-one-l-ol 1 and glacial acetic acid in benzene was added to pyrrolidine to give 2-methyl-l-pen ten-1-[N-pyrrolidinyl]-3-one 2. Compound 2 when treated with oxalyl chloride and methanol was added, 3,5-dimethyl-2-methoxycarbonyl-4-pyrone 3 was produced. Treatment of compound 3 with sodium borohydride in methanol gives 3,5-dimethyl-2-hydroxymethyl-4-pyrone 4. Compound 4 was converted to 3,5-dimethyl-2-hydroxymethyl-4-pyridone 5 by heating compound 4 with aqueous ammonia in a sealed flask. Compound 5 was converted to 4-chloro-2-chloromethyl-3,5-dimethyl pyridine 6 by treatment with phosphorous oxychloride. Treatment of compound 6 with 5-methoxy-2-mer-captobenzimidazole in tetrahydrofuran gave 2-[2-(4-chloro-3,5-dimethyl pyridinyl)methylthio]-5-methoxy benzimidazole 7. When compound 7 was treated with potassium hydroxide in dimethyl sulfoxide containing methanol, 2-[2-(3,5-dimethyl-4-methoxypyridinyl)methylthio]-5-methoxy... 

Optically pure P-lactam derivatives can also be prepared by an enantioselective photocyclization reaction of 2-pyridone in its inclusion complex with a chiral host. For example, irradiation of the 1 1 inclusion complex of 1 and 4-methoxy-/V-inethyl-2-pyridone (33) in the solid state gave (—)-34 of 100% ee... 

Pyridones may be selectively acylated at oxygen by treatment with acetyl chloride in acetone in the presence of potassium carbonate <2001JOC3646>. 2-Pyridones are also selectively O-acylated with 2-bromobenzoyl chlorides in high yield using potassium carbonate and tetrabutylammonium bromide (TBAB) in acetone <2003T3009>. For example 3-methoxy-2(17/)-pyridone is acylated in 88% yield by 2-bromobenzoyl chloride under these conditions (Equation 73). 

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