A Simple Synthesis of 2‐{(Arylmethylidene)hydrazinylidene]‐3‐hydroxy‐4H‐furo[3,2‐c]pyran‐4(3H)‐ones

A simple synthesis of 2‐hydrazinylidene‐3‐hydroxy‐4H‐furo[3,2‐c]pyran‐4‐ones is described. A mixture of (isocyanoimino)(triphenyl)phosphorane, an aromatic aldehyde, and dehydroacetic acid (=3‐acetyl‐2‐hydroxy‐6‐methyl‐4H‐pyran‐4‐one) undergo a 1 : 1 : 1 addition reaction under mild conditions to afford the title compounds in excellent yields.     

New approach to the synthesis of substituted 7H‐furo[3,2‐b]pyran‐7‐ones based on 5‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one derivatives

A convenient approach to the synthesis of the previously unknown 7H‐furo[3,2‐b]pyran‐7‐ones based on the intramolecular cyclization of carbonyl derivatives of 5‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one has been elaborated. Key intermediates in the synthesis of the target 7H‐furo[3,2‐b]pyran‐7‐ones are 3‐hydroxy‐6‐methyl‐2‐(2‐oxo‐2‐arylethyl)‐4H‐pyran‐4‐ones. They are formed as a result of multicomponent condensation of 5‐hydroxy‐2‐methyl‐4H‐pyran‐4‐one with arylglyoxals and 4‐methoxyaniline.     

Synthesis and reactivity of 6‐methyl‐4H‐furo[3,2c]pyran‐3,4‐dione

An efficient synthesis of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one by bromination of dehydroacetic acid in glacial acetic acid is described. Novel 4‐hydroxy‐6‐methyl‐3‐(2‐substituted‐thiazol‐4‐yl)‐2H‐pyran‐2‐ones have been prepared from the reaction of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with thioamides, thiourea, and diphenylthiocarbazone. The condensation reaction of 6‐methyl‐4H‐furo[3,2c]pyran‐3,4‐dione, obtained from the reaction of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with aliphatic amines, with benzaldehydes and acetophenones led to novel 2‐arylidene‐6‐methyl‐2H‐furo[3,2‐c]pyran‐3,4‐diones and 6‐(2‐arylprop‐1‐enyl)‐2H‐furo[3,2‐c]pyran‐3,4‐diones. The structure of all compounds was established by elemental analysis, IR, NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

The Stereoselective Total Synthesis of (6S)‐5,6‐Dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one via Prins Cyclization

The stereoselective total synthesis of an antiproliferative and antifungal α‐pyrone natural product (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one is described. The key steps involved are the Prins cyclization, Mitsunobu reaction, and ring‐closing metathesis reaction.     

New synthesis and reactivity of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with binucleophilic amines

3‐(Bromoacetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one was synthesized by the reaction of dehydroacetic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized from the reaction of bromo‐DHAA with alkanediamines, phenylhydrazines, ortho‐phenylenediamines, and ortho‐aminobenzenethiol. The obtained new products 3‐(2‐N‐substituted‐acetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐ones, 4‐hydroxy‐3‐[1‐hydroxy‐2‐(2‐phenylhydrazinyl)vinyl]‐6‐methyl‐2H‐pyran‐2‐one, 1‐(2,4‐dinitrophenyl)‐7‐methyl‐2,3‐dihydro‐1H‐pyrano[4,3‐c]pyridazine‐4,5‐dione, 3‐(3,4‐dihydroquinoxalin‐2‐yl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one/3‐(3,4‐dihydroquinoxalin‐2‐yl)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione, 6‐methyl‐3‐(3,4‐dihydroquinoxalin‐2‐yl)‐2H‐pyran‐2,4(3H)‐dione, and (E)‐3‐(2H‐benzo[b][1,4]thiazin‐3(4H)‐ylidene)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione were fully characterized by IR, ¹H and ¹³C NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

Copper(II)‐Catalyzed Synthesis of N‐Substituted‐3‐amino‐4‐cyano‐isoquinoline‐1(2H)‐ones by the Reaction of N‐Substituted‐2‐iodobenzamides with Malononitrile

A novel Cu(OAc)₂·H₂O catalyzed coupling reaction of N‐substituted‐2‐iodobenzamides with malononitrile to afford N‐substituted‐3‐amino‐4‐cyano‐isoquinoline‐1(2H)‐ones is described. The reaction proceeded in DMSO at 90°C for 5 h in nitrogen without external ligands.     

Efficient Synthesis of 1‐Arylquinoxalin‐2(1H)‐ones via Cyclocondensation of N‐Aryl‐Substituted 2‐Nitrosoanilines with Functionalized Alkyl Acetates

N‐Aryl‐substituted 2‐nitrosoanilines (=2‐nitrosobenzenamines) 1 , readily available by nucleophilic substitution of the ortho‐H‐atom in nitroarenes with arenamines, react with 2‐substituted acetic acid esters in the presence of a weak base giving 1‐arylquinoxalin‐2(1H)‐ones (Scheme 2). This cyclocondensation allows for the synthesis of compounds 2 – 4 , unsubstituted at C(3) or substituted by alkyl, aryl, ester, amide, and keto groups, in good to excellent yields (Tables 1–4).     

An Efficient Synthesis of N‐Substituted‐3‐aryl‐3‐(4‐hydroxy‐6‐methyl‐2‐oxo‐2H‐pyran‐3‐yl)propanamides by Four‐Component Reaction in Aqueous Medium

A mild and efficient synthesis of N‐substituted‐3‐aryl‐3‐(4‐hydroxy‐6‐methyl‐2‐oxo‐2H‐pyran‐3‐yl)propanamides via four‐component reaction of an aldehyde, amine, Meldrum's acid, and 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one in the presence of benzyltriethylammonium chloride (TEBAC) in aqueous medium is described. This method has the advantages of accessible starting materials, good yields, mild reaction conditions, and begin environmentally friendly.     

Diversity‐Oriented Synthesis of Novel 2′‐Aminospiro[11H‐indeno[1,2‐b]quinoxaline‐11,4′‐[4H]pyran] Derivatives via a One‐Pot Four‐Component Reaction

A sequential one‐pot four‐component reaction for the efficient synthesis of novel 2′‐aminospiro[11H‐indeno[1,2‐b]quinoxaline‐11,4′‐[4H]pyran] derivatives 5 in the presence of AcONH₄ as a neutral, inexpensive, and dually activating catalyst is described (Scheme 1). The syntheses are achieved by reacting ninhydrin ( 1 ) with benzene‐1,2‐diamines 2 to give indenoquinoxalines, which are trapped in situ by malono derivatives 2 and various α‐methylenecarbonyl compounds 4 through cyclization, providing the multifunctionalized 2′‐aminospiro[11H‐indeno[1,2‐b]quinoxaline‐11,4′‐[4H]pyran] analogs 5 . This chemistry provides an efficient and promising synthetic way of proceeding for the diversity‐oriented construction of the spiro[indenoquinoxalino‐pyran] skeleton.     

An Efficient Synthesis of 3‐(1H‐Tetrazol‐5‐yl)coumarins (=3‐(1H‐Tetrazol‐5‐yl)‐2H‐1‐benzopyran‐2‐ones) via Domino Knoevenagel Condensation,Pinner Reaction,and 1,3‐Dipolar Cycloaddition in Water

A novel straightforward synthesis of 3‐(1H‐tetrazol‐5‐yl)coumarins (=3‐(1H‐tetrazol‐5‐yl)‐2H‐1‐benzopyran‐2‐ones) 6 via domino Knoevenagel condensation, Pinner reaction, and 1,3‐dipolar cycloaddition of substituted salicylaldehydes (=2‐hydroxybenzaldehydes), malononitrile (propanedinitrile), and sodium azide in H₂O is reported (Scheme 1 and Table 2). This general protocol provides a wide variety of 3‐(1H‐tetrazol‐5‐yl)coumarins in good yields under mild reaction conditions.     

A Novel and Efficient Synthesis of 3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐ones (=3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐1‐benzopyran‐2‐ones)

An efficient one‐pot synthesis of 3‐[(4,5‐dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐one (=3‐[(4,5‐dihydro‐1H‐pyrrol‐3yl)carbonyl]‐2H‐1‐benzopyran‐2‐one) derivatives 4 by a four‐component reaction of a salicylaldehyde 1 , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, a benzylamine 2 , and a diaroylacetylene (=1,4‐diarylbut‐2‐yne‐1,4‐dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H‐1‐benzopyran‐2‐one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

Synthesis of 1‐Amino‐5,6‐diaryl‐3‐cyano‐1H‐pyridin‐2‐ones and 6,7‐Diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines from Isoflavones

The one‐step cyclocondensation of substituted isoflavones (=3‐phenyl‐4H‐1‐benzopyran‐4‐ones) with cyanoacetohydrazide in the presence of KOH afforded a mixture of 1‐amino‐5,6‐diaryl‐3‐cyano‐1H‐2‐pyridin‐2‐ones and 6,7‐diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines.     

Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

A Stereoselective Aldol Approach for the Total Syntheses of Two 6‐Alkylated 2H‐Pyran‐2‐ones

A simple and highly efficient stereoselective total synthesis of the 6‐alkylated pyranones (6R)‐6‐[(1E,4R,6R)‐4,6‐dihydroxy‐10‐phenyldec‐1‐en‐1‐yl]‐5,6‐dihydro‐2H‐pyran‐2‐one ( 1 ) and (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one ( 2 ) was developed using Crimmins' aldol reaction, SmI₂ reduction, Grubbs‐II‐catalyzed olefin cross‐metathesis, and Still's modified Horner? Wadsworth? Emmons reaction.     

Asymmetric Proline‐Catalyzed Addition of Aldehydes to 3H‐Indol‐3‐ones: Enantioselective Synthesis of 2,3‐Dihydro‐1H‐indol‐3‐ones with Quaternary Stereogenic Centers

The proline‐catalyzed addition of various aliphatic aldehydes to sterically hindered 2‐aryl‐substituted 3H‐indol‐3‐ones affords 2,2‐disubstituted 2,3‐dihydro‐1H‐indol‐3‐one derivatives with excellent enantioselectivities. In addition, the synthesis of a chiral derivative, (S)‐2‐(2‐bromophenyl)‐2,3‐dihydro‐2‐(2‐hydroxyethyl)‐1H‐indol‐3‐one, which can be used as an intermediate for the preparation of the natural product hinckdentine A was accomplished with a high level of enantioselectivity.     

Transformations of Methyl 2‐[(E)‐2‐(Dimethylamino)‐1‐(methoxycarbonyl)ethenyl]‐1‐methyl‐1H‐indole‐3‐carboxylate

A simple and efficient synthesis of novel 2‐heteroaryl‐substituted 1H‐indole‐2‐carboxylates and γ‐carbolines, compounds 1 – 3 , from methyl 2‐(2‐methoxy‐2‐oxoethyl)‐1‐methyl‐1H‐indole‐3‐carboxylate ( 4 ) by the enaminone methodology is presented.     

Synthesis of Certain Benzoheterocyclic Compounds from 2‐Hydroxyacetophenone via Cyclization and Ring‐closing Metathesis

Synthesis of some benzoheterocyclic compounds like substituted benzofurans, 4‐methyl‐2H‐chromenes and 3,4‐dihydro‐2H‐benzo[b]oxepin‐5‐ones from 2‐hydroxyacetophenone via base induced cyclization and ring‐closing metathesis (RCM) is described.     

Reactions of alkyl (z)‐2‐[(E)‐2‐ethoxycarbonyl‐2‐(2‐pyridinyl)‐ethenyl]amino‐3‐dimethylaminopropenoates with C‐ and N‐nucleophiles. the synthesis of fused pyranones,pyridinones and pyrimidinones

Alkyl 2‐[2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates 3 and 4 were transformed with C‐and N‐nucleophiles into β‐heteroaryl‐α,β‐didehydro‐α‐amino acid derivatives 13 ‐ 16 , substituted 3‐amino‐4H‐quinolizin‐4‐one 17, 2H,5H‐benzo[b]pyran‐2,5‐dione 18 and 19 , 2H,5H‐pyrano[4,3‐b]pyran‐2,5‐dione 20 , 2H,5H‐pyrano[3,2‐c]benzo[b]pyran‐2,5‐dione 21 , 2H‐1‐benzopyran‐2‐one 22 and 24 , pyrido[l,2‐a]pyrimidin‐4‐one 31–34 and 39 derivatives, and N‐heteroaryl‐1H‐imidazole‐4‐carboxylates 37 and 38 .     

A new direction in the alkylation of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with active methylene reagents

In this paper, we report a new synthesis route to 4H‐pyran derivatives and a plausible reaction mechanism. The interaction of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with different active methylene reagents gives rise to the cleavage and subsequent recyclization of the pyran ring to afford the corresponding 4H‐pyran derivatives.     

Ag3[PMo12O40]: An efficient and green catalyst for the synthesis of highly functionalized pyran‐annulated heterocycles via multicomponent reaction

A facile, efficient and eco‐friendly catalytic protocol was developed for the synthesis of medicinally important pyran‐annulated heterocycles via multicomponent reaction (MCR). Cyclocondensation of differently substituted aromatic aldehydes, malononitrile/ethyl cyanoacetate and various β‐dicarbonyl compounds in the presence of Ag₃[PMo₁₂O₄₀]?nH₂O as heterogeneous catalyst, in EtOH–H₂O, afforded diverse pyran‐fused chromene analogues. The merits observed for this approach were it being conducted via MCR, using commercially available or easily accessible starting materials in the presence of a green and easily separable heterogeneous and reusable catalyst, and affording high yields of desired products in very short reaction times with high purity in one‐pot fashion, thus providing a superior alternative approach for the synthesis of pyran‐annulated heterocycles.