Novel syntheses of 3-anilino-pyrazin-2(1H)-ones and 3-anilino-quinoxalin-2-(1H)-ones via microwave-mediated Smiles rearrangement

In this Letter, we report a novel approach to the preparation of 3-anilino-pyrazin-2(1H)-ones and 3-anilino-quinoxalin-2(1H)-ones from the corresponding 3-halo pyrazin-2-amines and 3-haloquinoxalin-2-amines, using a microwave-mediated Smiles rearrangement.     

Synthesis of 3,4-dihydrobenzo[g]isoquinoline-1(2H)-ones and 3,4-dihydroisoquinoline-1(2H)-ones skeleton via intramolecular electrophilic cyclization

An original alternative approach to isoquinolines based on the installation of a benzene nucleus on a performed heterocyclic ring. Synthesis of 3,4-dihydrobenzo[g]isoquinoline-1(2H)-ones and 3,4-dihydroisoquinoline-1(2H)-ones via intramolecular electrophilic cyclization of 3,4-disubstituted lactams is reported.     

The synthesis of phthalazin-1(2H)-ones and 3-hydroxyisobenzofuran-1(3H)-ones via the ring contraction of tropones

Phthalazin-1(2H)-ones and 3-hydroxyisobenzofuran-1(3H)-ones were synthesized by the reactions of tropones with hydrazines and alcohols, respectively, via the ring contraction.     

Synthesis of (Z)-1-benzylidene-3-(1H-indol-1-yl)-1H-indene-2,2(3H)-dicarbonitriles via three-component reaction of 2-alkynylbenzaldehyde, malononitrile, and indole

Three-component reaction of 2-alkynylbenzaldehyde, malononitrile, and indole under mild conditions is described, which generates the desired (Z)-1-benzylidene-3-(1H-indol-1-yl)-1H-indene-2,2(3H)-dicarbonitriles in moderate to good yields. This reaction proceeds smoothly with high selectivity. The tandem condensation, nucleophilic addition, and 5-exo-cyclization may be involved in the process.     

10-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methyl-1H,10H-pyrano[4,3-b] chromen-1-ones from a pseudo-multicomponent reaction and evaluation of their antioxidant activity

A series of novel 10-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-3-methyl-1H,10H-pyrano[4,3-b]chromen-1-ones were synthesized by a pseudo-three-component reaction of 4-hydroxy-6-methyl-2-oxo-2H-pyran-2-one (TAL) with 2-hydroxyarylaldehydes using different acids as catalysts and solvents. The approach relies on a regioselective cascade reaction involving two molar equiv of the TAL iteratively acting as active methylene in a Knoevenagel condensation and in a Michael addition. The antioxidant activity of the synthesized compounds were determined using the DPPH scavenging assay, being the results dependent on the nature and number of chromone substituents. The compound bearing an ortho-dihydroxy (catechol) moiety showed excellent activity at lower concentrations, while derivatives bearing alkoxy groups as substituents present pro-oxidant activity.     

Synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-ones via Pd-catalyzed regioselective cross-coupling reaction and cyclization

An efficient and novel route for the synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 via palladium-catalyzed site-selective cross-coupling reaction and cyclization process was described. Reaction of 3-bromo-4-trifloxy-quinolin-2(1H)-one 3 with arylboronic acid catalyzed by PdCl₂(PPh₃)₂ afforded 3-bromo-4-aryl-quinolin-2(1H)-one 4, which then reacted with 2-ethynylaniline 5 via Pd-catalyzed Sonogashira coupling and CuI-mediated cyclization leading to the desired 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 in good yields.     

Regioselective synthesis of 5-alkylidene and 5-(iodoalkylidene)-pyrrol-2(5H)-ones by halolactamisation of (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides

Stereo- and regioselective synthesis of 5-alkylidene (arylidene) and 5-(iodoalkylidene)-pyrrol-2(5H)-ones was achieved from (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides by halocyclisation reaction. Selectivity was found to be highly dependent on the nature of the substituents and on the temperature.     

An expedient approach to tetrahydrofuro[3,2-b]pyridine-2(3H)-ones via activation of pyridine N-oxide by triflic anhydride

The double addition of bis(trimethylsilyl) ketene acetals [R₁, R₂ = CH₃, -(CH₂)₅-] to pyridine N-oxide promoted by triflic anhydride under mild conditions generates N-[(trifluoromethane)sulfonyl-1,2-dihydropyridine-2,4-dicarboxylic acids 2a-b. Subsequent reaction of these acids upon iodolactonization conditions affords tetrahydrofuro[3,2-b]pyridine-2(3H)-ones 3a-b containing an exo-insaturation on the products as a result of an unexpected decarboxylation.     

Synthesis of substituted 3-furan-2(5H)-ones via an anthracene Diels-Alder sequence

Deprotonation then electrophilic quench of the lactone derived from the Diels-Alder addition adduct of anthracene and maleic anhydride gave α-substituted lactones in good yield. Of particular note was the reaction with chlorotrimethylsilane which gave only the C-silylated product. Flash vacuum pyrolysis (FVP) of the alkylated products afforded 3-substituted furan-2(5H)-ones in good overall yield.     

A non-catalytic regioselective approach to the synthesis of (E)-stilbenes from suitably functionalized 2H-pyran-2-ones

Highly functionalized (E)-stilbenes 3a-m and 4-aryl-6-styryl-pyran-2-ylidineacetonitriles 4a-b have been prepared and delineated through the ring transformation of 6-aryl-3,4-disubstituted-2H-pyran-2-ones 1 with commercially available (E/Z)-4-phenyl-3-buten-2-one 2 without the use of any catalyst.     

Isoquinolin-1(2H)-ones and 1,6-naphthyridin-5(6H)-ones by an N-acylation-SNAr sequence

A new synthesis of 2,3-dialkyl-4-carbomethoxyisoquinolin-1(2H)-ones and 6,7-dialkyl-8-carbomethoxy-1,6-naphthyridin-5(6H)-ones is reported. The process involves treatment of a β-enaminoester with 2-fluoro-5-nitrobenzoyl chloride, 2-fluorobenzoyl chloride or 2-chloronicotinoyl chloride followed by heating in the presence of base. The conversion, which proceeds by an N-acylation-S_NAr reaction sequence, affords 50–86% yields when R¹ is n-alkyl but ≤30% yields when R¹ is α-branched.     

One-pot synthesis of quinolin-2-(1H)-ones via tandem Ugi-Knoevenagel condensations

A new application of the Ugi reaction in the synthesis of heterocyclic compounds is described. Substituted quinolin-2-(1H)-ones are formed in one-pot sequential Ugi four-component condensation and intramolecular Knoevenagel cyclization between o-acylanilines, aldehydes, malonic or tosylacetic acids and cyclohexyl isocyanide.     

A general and efficient synthesis of substituted furans and dihydrofurans via gold-catalyzed cyclization of (Z)-2-en-4-yn-1-ols

A highly efficient Au-catalyzed cyclization of (Z)-enynols that proceeds under mild reaction conditions has been developed. This methodology provides rapid access to substituted furans and stereodefined (Z)-5-ylidene-2,5-dihydrofurans in a regioselective manner from suitably substituted (Z)-2-en-4-yn-1-ols.     

A simple and facile route for the synthesis of 2H-1,4-benzoxazin-3-(4H)-ones via reductive cyclization of 2-(2-nitrophenoxy)acetonitrile adducts in the presence of Fe/acetic acid

A simple route for the synthesis of 1,4-benzoxazin-3-(4H)-ones is described herein. This method involves the reductive cyclization of 2-(2-nitrophenoxy)acetonitrile adducts in the presence of Fe/acetic acid in good to excellent yields. This system was compatible with various other functional groups.     

Synthesis of 4H-1,3-benzoxazin-4-ones from 2,2-diazidobenzofuran-3(2H)-ones

Benzoxazine derivatives are useful building blocks and display various biological activities. We serendipitously discovered and subsequently developed a new one pot method for the synthesis of 2-(dimethyl amino)/2-morpholino/2- (piperidin-1-yl)-4H-benzo[e][1,3]oxazin-4-ones from corresponding substituted 2,2-diazidobenzofuran 3(2H) - ones and N-formyl dimethyl amine (DMF)/N-formylmorpholine/N-formylpiperidine using m-CPBA at 100?°C in moderate to good yields. We also demonstrated the utility of 4H-benzoxazines for the synthesis of other medicinally important compounds such as 2-hydroxyphenyl substituted 1,2,4-triazoles, unsymmetrical 1,3,5-triazines, and 1,2,4-oxadiazoles.     

A novel and facile synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones via a one-pot multi-component reaction

A simple and efficient synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones was achieved via a one-pot multi-component reaction of cyclohexyl isocyanide, an aldehyde, a 1,3-dicarbonyl compound, and ammonium acetate in the presence of a catalytic amount of KHSO₄ in acetonitrile.     

Photochemical synthesis of isomeric (E/Z)-3-alkylidene-3H-isobenzofuranones

The synthesis of isomeric (E/Z)-3-alkylidene-3H-isobenzofuranones by photoisomerization of 2-aroyl-2-methyl/benzylindan-1,3-diones in high yields is described.     

Base promoted facile route to functionalized benzo[b][1,8]naphthyridin-2-(1H)-ones from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides

A facile synthesis of 4-amino-N-benzylbenzo[b][1,8]naphthyridin-2(1H)-ones 3 is described from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides 2 with t-BuOK in excellent yields in mild conditions. These reactions proceeded at room temperature under aerobic atmosphere in very short period. The cyclization reactions were also extended with N-alkyl amino acetamide analogues affording the products in good yields.     

Studies on the Biginelli reaction: a mild and selective route to 3,4-dihydropyrimidin-2(1H)-ones via enamine intermediates

l-Proline methyl ester hydrochloride was found to be an effective catalyst for assembling (±)-dihydropyrimidinones under mild conditions. Mechanistic insights into the useful selectivity elements of this amine-catalyzed process are also reported.     

Unexpected dimerization during hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones

Palladium catalyzed hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones (1-3) gave besides the expected 2,α-dihydro products 8-10 pentacyclic dimers formed by an attack of a semihydrogenated species on the substrate.