Synthesis of pyridin-2(1H)-ones by the intramolecular cyclization of amides of β-enamino ketones

Abstract

Keywords: amide, β-enamino ketone, pyridin-2(1H)-ones, intramolecular cyclization.The sole example of intramolecular ring closing of β-amino ketone amides leading to pyridine-2(1H)-ones is the cyclization of pyridinium salts, formed from chloroacetamide 1a and pyridine, to 1-(1,2-dihydro-2-oxo-3-pyridinyl)pyridinium chloride 2 [1].With the aim of studying the possibility of a similar reaction for other representatives of β-enamino ketone amides we synthesized phenylacetamide 1b and tosylacetamide 1c. Compounds 1a,b have been obtained by the acylation of enamino ketone 3 [2] with the acid chloride of the corresponding carboxylic acid, compound 1c -by the reaction of chloroacetamide 1a with sodium p-toluenesulfonamide in DMF.It was established that cyclization does not occur under the action of an alcoholic solution of alkali on compound 1b. According to TLC data enamino ketone 3, the product of its hydrolysis was confirmed in the reaction medium. 4,6-Dimethyl-3-phenylpyridin-2(1H)-one (4) was successfully obtained in 53% yield on conducting the reaction in THF in the presence of potassium tert-butylate. However in this case also, according to chromato-mass spectrometry, enamino ketone 3 is the reaction by-product, obtained as a result of hydrolysis of compound 1b by the water formed on cyclization.Tosylacetamide 1c is converted into pyridine-2(1H)-one 5 even by the action of potassium carbonate in DMF solution. Nucleophilic substitution of chlorine by a tosyl group in compound 1a and cyclization of the resulting tosylacetamide 1c may be carried out as a one-pot synthesis. On interacting chloroacetamide 1a with sodium p-toluenesulfinate in the presence of potassium carbonate pyridin-2(1H)-one 5 is formed in 71% yield. The availability of the initial compounds, the simplicity of carrying out the experiment, and the good and satisfactory yields enable the conclusion to be made that such an approach to the synthesis of pyridin-2(1H)-ones is promising.

Intramolecular cyclization of N-(3-oxoalkenyl)phenylacetamides: synthesis of 3-phenyl-2(1H)-pyridones

“…The physical constants and spectral data of the compounds 3b, 7b were given earlier by us. 34 Copies of NMR spectra are given in the supporting information.…”

Trimethylsilyl Trifluoromethanesulfonate-Promoted Cyclocondensation of β-Ketoenamides and Subsequent Nonaflation to Pyrid-2-yl and Pyrid-4-yl Nonaflates as Flexible Precursors for Polysubstituted Pyridines

“…We were pleased to find that they were converted into the expected pyrid-2-ones 15a and 15b in good yields upon treatment with TMSOTf. For the cyclization of compound 14a the traditional conditions using KOt-Bu 16 allowed a shorter reaction time and provided a slightly higher yield (entry 2). For compound 14b, however, the TMSOTf-promoted condensation proved to be the superior method since the KOt-Bu protocol failed in this case (entry 4).…”

“…For compound 14b, however, the TMSOTf-promoted condensation proved to be the superior method since the KOt-Bu protocol failed in this case (entry 4). Using the latter protocol the acetylacetone (12b)-and heptan-3,5-dione (12c)-derived enamides 14c and 14d smoothly cyclized to the pyrid-2-ones 15c 16 and 15d (entries 5 and 6). In both cases a competing deacylation leading to the formation of the corresponding enamines 13b and 13c was observed.…”

“…Reactions were generally performed under argon in flame-dried flasks or sealed tubes; liquid components were added by syringe. 24 and 15c 16 were prepared according to literature procedures.…”