2-Methoxycarbonyl-4 -pyridones

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... 

Photolysis of benzene solutions of l-methoxycarbonyl-2-naphthylmethyl 2,6-di-methyl substituted phenyl ethers induces C-O cleavage with formation of 2,4-cyclohexadienone intermediates which are subsequently photo-rearranged into meta substituted phenols. In methanol, 9-anthrylmethoxy-pyrid-2-one or l-pyrenylmethoxypyrid-2-one undergo photoheterolysis to give the C-O heterolysis products l-hydroxypyrid-2-one and the arylmethyl methyl ether, together with 2-pyridone, aryl-substituted methanol and aryl aldehyde derived from homolysis of the N-O bond. Evidence shows that an intramolecular exciplex plays a crucial role in C-O bond heterolysis. 

The substituent effect on the tautomeric equilibrium in solution has been studied using experimental pKa values and UV spectra (in water at 20 °C) of several 4(177)-pyridones and their N- and O-fixed derivatives. It was concluded that most of the factors affecting the tautomerism of 4(l/7)-pyridones are due to the electronic effect, including steric effect, of the substituents in the 2-position. Thus, the proportion of the hydroxy form increases on introduction of an electron-withdrawing group into the 2-position. For example, 5-methoxy-4(l/7)-pyridones with a methyl, hydroxymethyl, and methoxymethyl groups in the 2-position exist essentially in the pyridone form however, 2-methoxycarbonyl-substituted derivative exists as a mixture of hydroxy and oxo form in water (77BCJ710). The effect of substituents in the 3-position... 

Temperature-jump experiments were performed with aqueous solutions of 2-chloro-4(l/7)-pyridone and 2,6-di(methoxycarbonyl)-4(17/)-pyridone (chelidamic acid dimethyl ester). It was suggested that when the tautomeric functional group is remote, tautomeric interconversion occurs through intermediate ionization and dissociation followed by ion recombination (77JA4438). 

The vinylogous aza-enone, A -methoxycarbonyl-5,6-dihydro-4-pyridone 31, has several advantages. It reacts with electron-rich as well as electron-poor alkenes to render cycloadducts in high yield and with extremely high regioselectivity [56], It should be noted that photoaddition of the analogous cyclohexenone derivatives show moderate or no regioselectivity toward the electron-rich or electron-poor alkenes 32a and 32c. 

Write out a mechanism for the conversion of 4-pyrone into l-phenyl-4-pyridone by reaction with aniline. Write structures for the products you would expect from reaction of methyl coumalate (5-methoxycarbonyl-2-pyrone) with benzylamine. 

The hydroxy adducts can be oxidized into the Sn products. Indeed, the oxidative hydroxylation of Al-alkylpyridinium salts into pyridones is a well-known Sn transformation, as illustrated by the reaction of 3-methoxycarbonyl-l-methylpyridinium iodide with the hydroxide ion in the presence of potassium ferricyanide, affording the corresponding l-methyl-6-pyridone (Scheme 37) [2, 11, 139]. 

Danishefsky etal. [61] reported an improved route to (20/ .J)-camptothe-cin in connection with their original total synthesis [60, 62-64], Reaction of tricyclic compound (14) with sodium hexamethyldisilazide and benzalde-hyde afforded a 90% yield of the benzylidene acid (15). A mechanism similar to a Stobbe condensation with participation of the methoxycarbonyl function on the pyridone ring is suggested for this reaction step. Ozonolysis of this compound (15) Scheme 2.2) afforded a 96% yield of the acid (16) which, upon esterification, provided (17) in 81% yield. Compound (17) is readily converted to (20/ S)-camptothecin. 

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