L-Methyl-2-pyridone

The corresponding [5,4-6]-compound (107) was prepared similarly and treated with methyl iodide to give a quaternary salt which was shown to have structure 108, because mild alkaline hydrolysis gave 3-acetamido-l-methyl-2-pyridone. Again, quaternization took place on the pyridine-nitrogen, which is different from the behavior of the corresponding 1,4-diazaindene mentioned above. 

FIGURE I A reconstructed extracted ion chromatogram of nicotinic acid and its six metabolites under HILIC conditions. Column Hypersil silica (4.6 X 50 mm) at a flow rate of 4 mL/min. Mobile phase A is water, mobile phase B is acetonitrile, both containing 1% formic acid. Gradient is 0.01-0.25 min 90% B to 65% B 0.25-0.90 min 65% B to 50% B. NA nicotinic acid NAM nicotinamide NUA nicotinuric acid 2-PY l-methyl-2-pyridone-5-carboxamide l-MNAM I-methyl-nicotinamide NAMO nicotinamide-N-oxide 4-PY l-methyl-4-pyridone-5-carboxamide. (Reprinted with permission from Reference 20.)... 

In order to clarify the reaction mechanism, 6-deuterio-labeled 3,5-dinitro-l-methyl-2-pyridone (87, 1 mmol) was prepared and heated with cyclohexanone (2 mmol) and ammonia (10 mmol). A mixture of 2-deuterio- (88) and 4-deuterio-3-nitro-5,6,7,8-tetrahydroquinoline (89) was obtained in the ratio 58 42 (Scheme III.49). 

Attempts to extend this process to the related 2-pyridone system have been less successful, with only a small proportion of C-6 lithiation being observed with l-methyl-2-pyridone [85CC1021 88JCS(P1)1]. In fact, the major mode of reaction involves lithiation of the exocyclic methyl group, to give a carbanionic species that is dipole-stabilized by the heterocyclic amide group (Scheme 120) (83MI1). 

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-... 

Aminopyridine and l-methyl-2-pyridone are sulfonated under milder conditions (H2S04-S03, 140°C) in the 5-position. 2,6-Di-r-butylpyridine is converted into the 3-sulfonic acid under mild conditions (S02-S03, 0°C) because reaction of S03 at the nitrogen atom is prevented sterically thus, reaction occurs on the free base, under conditions where this is the majority species. 

CdX2 (X = C104 or BF4) reacts with l-methyl-2-pyridone (L) to yield CdLeX2, while zinc yields only tetracoordinate ZnL4X2 complexes the ligand is bound via oxygen in both cases.715... 

Recently, it has been shown that 2-pyridones with the nitrogen atom substituted by alkyl,262 aryl, or methoxyl265 do undergo Diels-Alder reactions. Heating l-methyl-2-pyridone with DMAD to 195°, the first successful example studied,262 gave 51, which was thought to be formed via 49 as shown. Under milder conditions,265 Diels-Alder adducts (cf. 49) can be isolated and, on further heating, yield phthalic esters and isocyanates. 

Monobromination of these oxy compounds is difficult to achieve even at low temperatures and with low molar proportions of bromine. At - 10°C, bromine converted l-methyl-2-pyridone into a mixture of 3- and 5-bromo derivatives (1 2), but with 18% 3,5-dibromination as well. Reagents such as NBS at 10°C and dioxan dibromide were more effective giving a 1 4 ratio of 3- 5-bromo in a total yield of 56%, and a 1 1.3 ratio (with 8% dibromination) in a total yield of 81%, respectively (82CHE1284). 

Side-chain bromination frequently accompanies annular brominations when reagents or conditions conducive to homolytic reactions are used. When NBS in carbon tetrachloride reacted with l,3-dimethyl-2-pyridone a 96% yield of the 5-bromo derivative resulted with added benzoyl peroxide the product was 3-bromomethyl-l-methyl-2-pyridone (63%) (76JOC2065), and there are other examples (85CHE1399). 

Electrochemical fluorination of pyridine in the presence of a source of fluoride ion gave 2-fluoropyridine in 22% yield (85M11). With xenon difluoride, pyridine formed 2-fluoropyridine (35%), 3-fluoropyridine (20%), and 2,6-difluoropyridine (11%) in a reaction unlikely to be a conventional electrophilic substitution. Xenon hexafluoride has also been used (76JFC179). With cesium fluoroxysulfate at room temperature in ether or chloroform, the major product was 2-fluoropyridine (61 and 47%, respectively). Some 2-chloropyridine was also formed in chloroform solution. In methanol the entire product was 2-methoxypyridine (90TL775). Fluorine, diluted with argon in acetic acid, gave a 42% yield of the 5-fluoro derivative of l-methyl-2-pyridone [82H( 17)429],... 

Books sometimes disagree on the preferred tautomer of guanine—6.f versus 6.g. A parallel can be found in 2-pyridone, which also has two likely tautomeric forms, 6.h and 6.i. To determine which form of 2-pyridone predominates, the ultraviolet spectra of two isomers, l-methyl-2-pyridone (6.j) and 2-methoxypyridine (6.k), were obtained with the observed Amax wavelengths shown. The Amax of 2-pyridone is at 229 nm. Does 2-pyridone likely favor tautomer 6.h or 6.i Which tautomer of guanine is likely favored, 6.f or 6.g (Elguero, J., Marzin, C., Katritzky, A. R., Linda, P. The Tautomer-ization of Heterocycles. Adv. Heterocycl. Chem., Suppl. 1 New York Academic Press, 1976.)... 

Hydroxy-3-methylpyridine was hydrogenated to 3-methyl-2-piperidone in an 80% yield over Raney Ni in methanol at 200-240°C and 12 MPa H2 (eq. 12.28).40 At 280°C, hydrogenolysis to give 3-methylpiperidine and A-alkylation to give 1,3-di-methylpiperidine took place. In contrast, l-methyl-2-pyridone is hydrogenated under much milder conditions to the corresponding 2-piperidone over Raney Ni in ethanol (eq. 12.29).41... 

This type of isomerization is much more common in carbonyl-containing rings. A well-known example is the generation of cyclobutadiene by photolysis of pyran-2-one with the loss of CO2. l-Methyl-2-pyridone 24 (XY = MeNC=0, Z = CH) gives 25 (XY = MeNC=0, Z = CH) l,3-oxazin-6-ones 24 (XY = 0C=0, Z = N) form the corresponding bicycles, which can eliminate CO2, and the l,2,3-benzotriazin-4-ones similarly give the corresponding benzazetones. 

Pyranones undergo DielsAlder reactions with maleic anhydride adducts of type 408 are formed which can lose carbon dioxide and react with more anhydride to give 409. 2-Pyranones also react with singlet oxygen to give endoperoxides 410. Benzyne reacts with l-methyl-2-pyridone to give 411. 

The tautomeric 6-hydroxy-7-azaindole shows a shift to longer wavelength, which is characteristic of 2-hydroxypyridine as the neutral molecule or of l-methyl-2-pyridone. The degree of tauto-merization is solvent-dependent, and Yakhontov et have determined the lactam/lactim R = Me) ratio from the position of... 

Methylpyridinium 3-carboxylate, 515 1-MethyIpyridinium methyl sulfate, 932 l-Methyl-2-pyridone, 932... 

When l-[14C]methyl-pyridinium aldoxime iodide or radioactive pralidoxime [14C]-labelled in the oxime group was parenterally administrated to rats, 90% of the radioactivity was recovered in urine and 6% in the faeces, irrespective of the position of the label. About 90% of the urinary radioactivity was associated with intact pralidoxime. In addition, some 5% of the dose was excreted as l-methyl-2-pyridone, indicating some cyanogenesis (Enandcret al., 1962). In humans, the l-methyl-2-cyanopyridinium ion was detected in urine of male volunteers without significantly increased urinary thiocyanate. Since 90% of pralidoxime chloride, 5 mg kg 1 IV, was recovered from urine, cyanide formation is probably of no toxicological concern (Garrigue etal., 1990). 

Nitro- 1-methyl -2-pyridon Methanol 65 24 3-Amino-l-methyl- 2-pyridon -100 ... 

Methyl-2-piperidon1 440 g (4,0 Mol) l-Methyl-2-pyridon werden in 700 ml 99%-igem Athanol nach Zu-gabe von 50 g Raney-Nickel bei 507150 bar 4 Stdn. hydriert. Nach dem Erkalten wird filtriert, iiber Natriumsul-fat getrocknet, i. Vak. eingeengt und rektifiziert Ausbeute 472,2 g (96°/o d.Th.) Kp12 90-97°. 

Of the 4-pyridone series, Jackman et al.280 have reported that 1-methyl-4-pyridone sustains a weaker ring current than l-methyl-2-pyridone, and Batts and Spinner281 in a discussion of chemical shifts state that the fractional aromaticity is probably not appreciable for either (4-pyridone or 4-pyridone imine). ... 

When 1 is subjected to the carboxylate anion of 3 (TEA, R1CO2H), 2-acyloxy-l-methylpyridinium iodide (2) is formed. The hydrogen halide (HC1) is scavenged with triethylamine. A nucleophile (NuH) (4) such as an amine or alcohol in the presence of TEA adds to the carbonyl center of 2, yielding the desired product 5 and the by-product, l-methyl-2-pyridone (6). 

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