Oxidative Methyl Esterification of Primary Alcohols with Iodine‐Mediated Poly[4‐(Diacetoxyiodo)Styrene]

An operationally simple oxidative methyl esterification of primary alcohols in good yields using an iodine‐mediated poly[4‐(diacetoxyiodo)styrene] in methanol at room temperature is described. The polymeric reagent can be regenerated and reused as an environmentally benign reagent.     

A Novel One‐Pot Synthesis of Fully Substituted Thiophen‐2(3H)‐ones Using N,N‐Disubstituted Thioamides

A new one‐step synthesis of highly substituted thiophen‐2(3H)‐one derivatives was developed. 2‐Aryl‐1‐(morpholin‐4‐yl)ethanethiones were reacted with 2‐chloro‐2‐phenylacetyl chloride in DMF in the presence of a base to give the title compounds in moderate‐to‐good yields.     

Facile Heterocyclic Synthesis and Antibacterial Activity of Substituted Isoxazol‐5(4H)‐ones

An efficient, simple, and green procedure for the synthesis of isoxazol‐5(4H)‐one derivatives are described here through a convenient one‐pot, three‐component reaction at room temperature. The title compounds are isolated in high to excellent yields and after short reaction times, and are characterized by various spectroscopic methods such as IR, ¹H NMR, and ¹³C NMR. The synthesized compounds 4a–c and 4e–i were tested for their in vitro activity against a panel of Gram‐positive and Gram‐negative bacteria, demonstrating their ability to inhibit microorganisms with a zone of inhibition ranging from 15 to 30 mm, minimum inhibitory concentration between 250 and 900 μg/mL, and minimum bacterial concentration between 700 and 1000 μg/mL.     

Synthesis of 3‐Alkoxybenzo[c]thiophen‐1(3H)‐ones by Hydrolysis of N‐Substituted 3‐Alkoxybenzo[c]thiophen‐1(3H)‐imines Derived from 1‐Bromo‐2‐(dialkoxymethyl)benzenes and Isothiocyanates

A convenient procedure for the preparation of a new type of thiophthalides, 3‐alkoxybenzo[c]thiophen‐1(3H)‐ones 4 and 9 has been developed. Thus, 1‐(dialkoxymethyl)‐2‐lithiobenzenes, generated by Br/Li exchange between 2‐bromo‐1‐(dialkoxymethyl)benzenes 1 and 6 , and BuLi, react with isothiocyanates to afford N‐substituted 2‐(dialkoxymethyl)benzothioamides 2 and 7 , which, on treatment with a catalytic amount of TsOH?H₂O, give N‐substituted 3‐alkoxybenzo[c]thiophen‐1(3H)‐imines 3 and 8 . The latter are hydrolyzed under acidic conditions to the desired products 4 and 9 , respectively.     

Synthesis and Structure of 2‐Substituted Thieno[3′,2′:5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one Derivatives

A series of new 2‐substituted 3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 8 were synthesized via an aza‐Wittig reaction. Phosphoranylideneamino derivatives 6a or 6b reacted with 4‐chlorophenyl isocyanate to give carbodiimide derivatives 7a or 7b , respectively, which were further treated with amines or phenols to give compounds 8 in the presence of a catalytic amount of EtONa or K₂CO₃. The structure of 2‐(4‐chlorophenoxy)‐3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one ( 8j ) was comfirmed by X‐ray analysis.     

Synthesis of Furo[2,3‐d]pyridazin‐4(5H)‐one and Its N(5)‐Substituted Derivatives

We report the efficient preparation of furo[2,3‐d]pyridazin‐4(5H)‐one and its N‐substituted derivatives starting from methyl 2‐methylfuran‐3‐carboxylate. The Me group was converted to the aldehyde group, which was then condensed with hydrazine derivatives. Then, the ester functionalities were hydrolyzed to the corresponding acids, followed by treatment with SOCl₂ to give N‐substituted furopyridazinone derivatives.     

Ring Opening of 2‐(Benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones and 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones

Substituted 2‐(benzylamino)‐2H‐1,4‐benzoxazin‐3(4H)‐ones are unstable under alkaline and acidic conditions, undergoing opening of the benzoxazinone ring. 2‐Bromo‐2H‐1,4‐benzoxazin‐3(4H)‐ones show similar degradation under alkaline conditions, while replacement of Br at C(2) to give 2‐hydroxy‐2H‐1,4‐benzoxazin‐3(4H)‐ones was observed only under mild alkaline conditions. Mechanisms of ring opening and degradation to 2‐aminophenol derivatives are proposed.     

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.     

Cp2ZrCl2‐catalyzed synthesis of 2‐substituted quinozolin‐4(3H)‐ones

Zirconocene dichloride (Cp₂ZrCl₂) in the presence of DMF was found to be a highly efficient catalyst for the synthesis of structurally diverse 2‐substituted quinozolin‐4(3H)‐ones by reaction of anthranilimide with a wide range of aryl aldehydes. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of Derivatives of Pyrido[4,3‐d]pyrimidin‐4(3H)‐one via an Iminophosphorane

A series of new, 2‐substituted 3‐aryl‐8,9,10,11‐tetrahydro‐5‐methyl[1]benzothieno[3′,2′ : 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones, compounds 5a – q , were designed and synthesized via the aza‐Wittig reaction as the key step. The iminophosphorane 1 reacted with phenyl isocyanate (or 4‐chlorophenyl isocyanate) to the carbodiimide 4 , which was cyclized to 5 upon addition of different amines, EtOH, or phenols in the presence of a catalytic amount of EtONa or K₂CO₃ (Schemes 1 and 2). The structures of compounds 5 were confirmed by IR, ¹H‐ and ¹³C‐NMR, EI‐MS, elemental analyses, and, in the case of 5l , by single‐crystal X‐ray diffraction (Figure).     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

Efficient Iminophosphorane‐Mediated Preparation of Benzofuro[3,2‐d]pyrimidin‐4(3H)‐ones and Unexpected Ring Opening Products

The carbodiimides 4 , obtained from aza‐Wittig reactions of iminophosphorane 3 with aromatic isocyanates, reacted with secondary amines, phenols or alcohols in the presence of catalytic amounts of K₂CO₃ or sodium alkoxide to give 2‐substituted benzofuro[3,2‐d]pyrimidin‐4(3H)‐ones 6 . However, when 2,2′‐iminobis[ethanol] was used, the unexpected ring opening product 7 was formed instead of 6 . Reaction of 4 with primary amines RNH₂ (R=Et, Pr, Bu, etc.) gave guanidine intermediates 8 , which were further treated with EtONa to give only one regioisomer 9 via a base catalyzed cyclization. However, another regioisomer 11 was obtained when NH₃ or ‘small’ amines RNH₂ (R=Me, NH₂) were used in the absence of EtONa via a spontaneous cyclization of 8 .     

Synthesis of 4‐halo‐2 (5H)‐furanones and their suzuki‐coupling reactions with organoboronic acids. A general route to 4‐aryl‐2 (5 H) ‐furanones

4‐Halo‐2(5H)‐furanones were prepared by the halolactonization of 2,3‐allenoic acids. The subsequent Suzuki coupling reaction of 4‐halo 2(5H)‐furanones with aryl boronic acids was carried out to produce 4‐aryl‐2(5H)‐furanones in excellent yields.     

Synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones using nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 nanoparticles

Nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl₂ (nano‐[Zn‐2BSMP]Cl₂) as a nanoparticle Schiff base complex and a catalyst was introduced for the solvent‐free synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones by the multicomponent condensation reaction of various aromatic aldehydes, β‐naphthol, ethyl acetoacetate, and phenyl hydrazine at room temperature.     

Design,Synthesis, and Evaluation of 3‐((4‐(t‐Butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones as Neuraminidase Inhibitors

A series of novel 3‐((4‐(t‐butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones ( 7a – 7z ) were designed, synthesized and evaluated for their ability of inhibiting neuraminidase (NA) of in?uenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 7l with the scaffold of 2‐(2‐(2‐methoxybenzylidene)hydrazinyl)thiazole was the best one, exhibiting moderate NA inhibitory activity with IC₅₀ of 44.66 µmol/L. Structure‐activity relationship showed that compounds with methoxy or hydroxy groups at the ortho position, fluorine and nitro groups at the meta position and chlorine and bromine groups at the para position of phenyl ring were more active. Docking study indicated that compound 7l has important interactions with some key residues (including Asp151, Glu119, Arg292, Tyr406, and Asn347) and binds to 430‐cavity adjacent to NA active site.     

A One‐Pot Biginelli Synthesis of 6‐Unsubstituted 5‐Aroylpyrimidin‐2(1H)‐ones and 6‐Acetyl‐1,2,4‐triazin‐3(2H)‐ones

The three‐component Biginelli‐like cyclocondensation reaction of enamines 1 , urea, and aldehydes in dioxane/acetic acid efficiently afforded the corresponding 6‐unsubstituted 3,4‐dihydropyrimidin‐2(1H)‐ones 2 in good yields (Scheme 1, Table). The corresponding reaction of azaenamine (=hydrazone) 7 with benzaldehyde and urea afforded 6‐acetyl‐1,2,4‐triazin‐3(2H)‐ones in good yields (Scheme 3).     

Synthesis of Some Quinazoline‐2(1H),4(3H)‐dione Derivatives

Several quinazoline‐2(1H),4(3H)‐dione derivatives were synthesized from pyrimidine‐2(1H),4(3H)‐dione derivative.     

An Efficient Synthesis of 4‐Arylmethylidene‐3‐substituted‐Isoxazol‐5(4H)‐ones in Aqueous Medium

A series of 4‐arylmethylidene‐3‐substituted‐isoxazol‐5(4H)‐ones were efficiently synthesized by eco‐benign, one pot uncatalyzed reaction of β‐keto‐ester, hydroxylamine hydrochloride, and aromatic aldehyde with electron donating substituent in water.     

Synthesis of 2‐Aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones by Deprotective Cyclization of N‐{3‐[(2E)‐3‐Arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides in Water

A new and convenient method for the preparation of 2‐aryl‐2,3‐dihydro‐1,8‐naphthyridin‐4(1H)‐ones 4 has been developed. Thus, N‐{3‐[(2E)‐3‐arylprop‐2‐enoyl]pyridin‐2‐yl}‐2,2‐dimethylpropanamides 3 are synthesized from commercially available pyridin‐2‐amine using an easily performed three‐step sequence and are subjected to cyclization with deprotection under acidic conditions in H₂O to give the desired products. Similarly, 2‐aryl‐2,3‐dihydro‐1,7‐naphthyridin‐4(1H)‐ones 8 and 2‐aryl‐2,3‐dihydro‐1,6‐naphthyridin‐4(1H)‐ones 12 can be prepared from pyridin‐3‐amine and pyridin‐4‐amine, respectively.     

A Novel Method for the Synthesis of 4(3H)‐Quinazolinones

Different metal perchlorates were screened to catalyze the three‐component reaction of anthranilic acid, triethyl orthoformate and amines to afford quinazolin‐4(3H)‐ones in solvent‐free conditions. Ni(ClO₄)₂ or Zn(ClO₄)₂ was demonstrated to be efficient to catalyze the reaction.