4-Pyridone, acetylation

From monoalkylammobutenones and diketene at —5°C in benzene 3-acetyl-4-methyl-2(l//)-pyridones 300 are formed via the intermediate amides 299 (80MI1). 

QHjLiN 26954-25-6) see Tirofiban hydrochloride (4-pyridinylthio)acetyl chloride (CiH ClNOS 52998-13-7) see Cefapirin 4(l f)-pyridone... 

The Liebeskind group cross-coupled 4-chloro-2-cyclobutenone 69 with 2-tribuylstannyl-benzothiazole to synthesize a-pyridone-based azaheteroaromatics [48], The adduct 70 underwent a thermal rearrangement to afford a transient vinylketene 71, which then intramolecularly cyclized onto the C—N double bond of benzothiazole, giving rise to thiazolo[3,2-a]pyridin-5-one 72. In another case, 2-acetyl-4-trimethylstannylthizaole (73) was coupled with an acid chloride 74 to form the desired ketone 75 [49]. 

Crystal-structure-sensitive bond-forming and -breaking processes other than ring-chain tautomerism are also known. For example, acetylation of 4-pyridone in pyridine gives rise to crystalline A-acetyl-4-pyridone. When this is dissolved in CH2C12 it gives a nearly 1 1 equilibrium mixture of this acetyl pyridone and 4-acetoxypyridine. The A-acetyl derivative is obtained by crystallization (79). 

Cyclodehydration of l-carboxymethyl-2-pyridone with acetic anhydride and perchloric acid gave the corresponding 1,3-oxazolonium perchlorate which with triethylamine gave the dimer (72) directly. Similar dimerization of other meso-ionic l,3-oxazol-5-ones (66) have been reported. The monomer (71) could not be isolated, but acetyl (67, R = Me) and benzoyl (67, R = Ph) derivatives were prepared from a... 

Trifluoromethyl [ F]hypofluorite Acetyl [ F]hypofluorite Perchloryl f Flfluoride Xenon d/[ F]fluoride 1-[ F]Fluoro-2-pyridone AZ-f FlFluoropyridinium triflate A/-[ F]Fluoro-A/-alkylsulphonamides Bromo [ F]fluoride... 

The reactions of 2-substituted 6-methyl-4/7-l,3-oxazin-4-ones 98 with isoxazole ketones 99 in the presence of potassium / -rt-butoxide furnished 3-acetyl-5-(3-methylisoxazol-5-yl)-2-pyridones 101 in good to excellent yields (Scheme 14). The formation of 2-pyridones 101 presumably proceeds via nucleophilic addition of the methylene carbon of 99 to the carbon atom at position 2 of the l,3-oxazin-4-ones 98, followed by ring opening to give the acetoacetyl intermediates 100, which are transformed into 101 by intramolecular aldol condensation <2005H(66)299>. 

Pyrano-fused heterocycles, namely pyrano[3,2-f]quinoline-2,5(6//)-diones, pyrano[3,2-f]benzopyran-2,5(6//)-dione, and pyrano[3,2-f]pyridine-2,5(67T)-diones, have been efficiently prepared by the condensation of 4-hydroxy-2-(l//)-quinolines, 4-hydroxycoumarin, or 4-hydroxy-(17/)-pyridone with a-acetyl-y-butyrolactone or the sodium salt of a-formyl-y-butyro-lactone in the presence of ammonium acetate <1999JHC467>. 

Ridi et al.3S report 1,2-diacetylation of pyrazolo[3,4-f>]pyridone 29b with acetic anhydride, which contrasts with the O-acetylation observed for similar systems (Section III,B,6). 

Kato et al,94 reported that 2-amino-6-methylpyridine and diketene did not yield 4-oxo-4/f-pyrido[l,2-a]pyrimidines but instead yielded 2-acetyl-acetamido-6-methylpyridine and pyridone or pyrone derivatives. 2-Methyl-4-oxo-4H-pyrido[l,2-a]pyrimidine (47) and its 8-methyl derivative have also been prepared from 2-aminopyridine and 2-amino-4-methylpyridine with N,N-dimethyl-3-aminocrotonamide95 or with acetoacetamide45 in yields of 5 and 39°,. respectively. 

The nitration of 6-phenyl-2-pyridone (70% nitric acid or nitronium tetra-fluoroborate at RT) produces 3-nitro-6-phenyl-2-pyridone (up to 60% yield). However, nitration at 90°C with 70% nitric acid is reported to give 3-nitro-6-(4-nitrophenyl)-2-pyridone (36%), whereas at 90°C acetyl nitrate yields 50% of a mixture of 3- and 5-nitro-6-phenyl-2-pyridone (72KGS1374). 

Mechanisms for the Reactions of the Anomeric Tetra-O-acetyl-D-glucopyranosyl Bromides with Pyridine and 2-Pyridone, R. U. Lemieux and A. R. Morgan, Can. J. Chem., 43 (1965) 2214-2221. 

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). 

CR(Q(262)1017>. The nucleophilic reactivity of the oxygen atom has been observed in the acetylation by acetic anhydride of 2-aryl- and 2-heteryl-A2-thiazolin-4-ones (Scheme 136). 2-Alkoxy and 2-methyl derivatives of A2-thiazolin-4-one (196) react with OPCl3 to yield thiazolylphosphoric esters (197) which have insecticidal uses (Scheme 137). An example of the electrophilic reactivity of the C-4 atom is the easy formation of oxime and phenylhydrazone derivatives. 5-Aryl-A2-thiazolin-4-one (198) gives the 1,3-dipolar cycloaddition product (199) with methyl fumarate and methyl maleate (Scheme 138). Under similar conditions, treatment of (198) with dimethyl acetylenedicarboxylate (DMAD) yields a thiophene derivative (202) when R = Ph and a pyridone derivative (203) when R = H (Scheme 139). The proposed mechanism involves the formation of a mesoionic intermediate (200) which reacts in a cycloaddition with a second molecule of DMAD, yielding (201), the decomposition of which depends on the R substituent. 

Narsaiah and Krishnaiah (2002) reported that the hetero-Diels-Alder reaction of A(-acetyl perflnoroalkyl substituted 2(1//) pyridones with DMAD on neutral alumina under solvent-free microwave irradiation conditions extended to undergo an inverse electron demand hetero-Diels-Alder reaction, resulting exclusively in E, Z isomers (3 1) of Michael-type A-adducts. 

Similarly, treatment of 2-trimethylsilyloxypyridine (46) with a-acetobromoglucose and silver perchlorate in nitromethane at 20° yielded l-(2,3,4,6-tetra-0-acetyl-D-glucopyranosyl)-2-pyridone (47) as the sole product.46 47 On the other hand, 2-ethoxypyridine (vide supra) gave a mixture of 0- and V-glycosyl derivatives.42,43... 

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