Synthesis of 2H-pyran-2-ones and fused pyran-2-ones as useful building blocks

Abstract

A one-pot synthesis of 3-benzoylamino derivatives of 5-to 8-membered cycloalka[b]pyran-2-ones 5 and 2H-pyran-2-ones 10, starting from the appropriate alkanones 1 and 8, respectively, N,N-dimethylformamide dimethyl acetal (DMFDMA) and hippuric acid in the presence of a large excess of acetic anhydride, is described. A comparison of conventional thermal activation with microwave activation is given in the case of synthesis of 5c. The benzoyl protective group on amino moiety of the fused pyran-2-ones 5 and derivatives 11 was successfully removed by gentle heating in sulfuric acid resulting in the formation of the corresponding 3-aminocycloalka[b]pyran-2-ones 7 and 3-amino-2H-pyran-2-ones 12 in high yield.

Design, Synthesis and Evaluation of Fused Bicyclo[2.2.2]octene as a Potential Core Scaffold for the Non-Covalent Inhibitors of SARS-CoV-2 3CLpro Main Protease

“…The first step ( Scheme 2 ) [ 46 , 47 , 48 , 49 ] of the synthetic route is thus a neat reaction of a suitable carbonyl compound 1a – e possessing an activated α-CH 2 unit with an appropriate C 1 synthon (DMFDMA ( 2a , R 1 = H) in all cases, except for 5b , where the incorporation of 4-methyl group in the 2 H -pyran-2-one product requires the use of a different C 1 synthon, i.e., DMADMA ( 2b , R 1 = Me)), thus forming N , N -dimethylaminomethylenes 3a – f . Thereafter, excess of 2 and methanol (formed as the side product) are removed with vacuum distillation and to the viscous remainder, containing intermediates 3a – f , hippuric acid ( 4 ) and acetanhydride are added.…”

“…The starting bicyclo[2.2.2]octenes 9a – f were prepared from appropriately substituted 2 H -pyran-2-ones 5a – f and maleic anhydride under reflux in tetralin according to the published procedure [ 50 ]. The synthesis of starting 2 H -pyran-2-ones 5a – f starts from appropriate carbonyl compounds 1a – f containing activated CH 2 groups (i.e., 4-methoxyphenylacetone, 3,4-dimethoxyphenylacetone, or ethyl acetoacetate), C 1 synthon 2a , b (DMFDMA or DMADMA), and hippuric acid ( 4 ) upon heating in acetic anhydride, as described previously [ 46 , 47 , 48 , 49 ].…”

Palladium-Catalyzed One-Pot Highly Regioselective 6-Endo Cyclization and Alkylation of Enynoates: Synthesis of 2-Alkanone Pyrones

“…Pyrones are fundamental structural motifs in numerous natural products and also versatile building blocks for the synthesis of various biologically active heterocyclic compounds . As a result, considerable attention has been devoted to preparing diverse pyrone compounds by employing different methods .…”

Ring switching tricomponent synthesis of pyrano[2,3-b]pyridine multifunctional derivatives

“…The synthesis of such heterocyclic systems in three-component condensation reactions has been described for phenols, naphthols, or hydroxy-substituted heterocycles but not for azaheterocycles containing amido-or imido-moieties. [8][9][10][11] Herein, we have proposed a convenient synthesis of substituted 8-aza-7-hydroxycoumarins based on the abovementioned general synthetic approach. Continuing the study of the Erlenmeyer-Pöchl reaction 12 and multicomponent condensations with 3-cyano-4methylpyrimidine-2,6-dione and orthoformates, 13 we have performed the three-component assemling of 3-cyano-4methylpyridine-2,6-dione 1 with triethyl orthoformate and a number of N-acylglycines 2a-g under the Erlenmeyer-Plöchl conditions (Scheme 1).…”

“…As a result, two types of intermolecular stacking interactions are produced, one between two symmetry-equivalent pyridine rings and one between the pyridine ring and the phenyl group; the corresponding centroid-centroid distances, angles between the planes and their shifts are 3.7685( 16) and 3.7440(13) Å, 0.0(2) and 7.19(6)°, 1.660(2) and 1.407(2) Å, respectively. The amino group is involved in a rather weak N-H (11)°] with the oxo group at the pyranopyridine moiety, thus producing a centrosymmetric dimer from the neighbouring molecules of 3f. Other weak interactions, such as C-H…”