Synthesis of Ethyl 2‐Amino‐4‐benzoyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carboxylates by a One‐pot,Three‐Component Reaction in the Presence of TPAB

In this research, in order to synthesize a series of ethyl 2‐amino‐4‐benzoyl‐5‐oxo‐5,6‐dihydro‐4H‐pyrano[3,2‐c]quinoline‐3‐carboxylates, a green and an efficient method is proposed through one‐pot three‐component reaction of substituted arylglyoxals, ethyl cyanoacetate, and 4‐hydroxyquinolin‐2(1H)‐one in the presence of terapropylammonium bromide as a catalyst in good yields. All synthesized new substances were characterized by FTIR, ¹H‐NMR, and ¹³C‐NMR spectral data and elemental analysis.     

A Green Synthesis of 7‐amino‐5‐(4‐aroyl)‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4,5,8‐hexahydropyrido[2,3‐d]pyrimidine‐6‐carbonitrile Derivatives by a One‐pot Three‐component Reaction

The synthesis of polyfunctionalized 7‐amino‐5‐(4‐aroyl)‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4,5,8‐hexahydropyrido[2,3‐d ]pyrimidine‐6‐carbonitrile derivatives by a green approach was achieved via one‐pot three‐component reaction of arylglyoxals, malononitrile, and 1,3‐dimethyl‐6‐aminouracil in the presence of urea as organocatalyst in EtOH:H₂O (1:1) at 60°C. This protocol provides a mild and fast procedure to structurally diverse bicyclic pyridopyrimidines in good to excellent yields.     

The reaction of (N‐isocyanimino) triphenylphosphorane with (E)‐3‐aryl‐2‐ propenoic acid derivatives: One‐pot synthesis of 2‐[(E)‐2‐aryl‐1‐ethenyl]‐1,3,4‐oxadiazoles via intramolecular aza‐Wittig reaction

The reaction of (E)‐3‐aryl‐2‐propenoic acid derivatives with (N‐isocyanimino) triphenylphosphorane proceeds smoothly at room temperature to afford the corresponding 2‐[(E)‐2‐aryl‐1‐ethenyl]‐1,3,4‐oxadiazole via an intramolecular aza‐Wittig reaction in good yields under neutral conditions. The structures of the products were deduced from their IR, ¹H NMR, and ¹³C NMR spectra and mass spectrometry. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:612–616, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20701     

One‐Pot Synthesis of 13‐Acetyl‐9‐methyl‐11‐oxo(or thioxo)‐8‐oxa‐10,12‐diazatricyclo[7.3.1.02,7]trideca‐2,4,6‐trienes under Microwave Irradiation

Oxygen‐bridged monastrol analogs, 13‐acetyl‐9‐methyl‐11‐oxo(or thioxo)‐8‐oxa‐10,12‐diazatricyclo[7.3. 1.0^2,7]trideca‐2,4,6‐trienes, were synthesized by one‐pot three component condensation reaction of substituted salicylaldehyde, acetylacetone and urea or thiourea with nontoxic, inexpensive, and easily available NaHSO₄ as catalyst under microwave irradiation and solvent‐free conditions in short time with good yields. The structures of the products were characterized by IR, ¹H NMR, ¹³C NMR spectra, and elemental analyses.     

Synthesis of 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

立体选择性合成2-(a-噻吩甲酰基)-3-取代苯基-4-乙氧羰基-5-甲基-反式-2,3-二氢呋喃

溴化(a-噻吩甲酰基)甲基三苯鉮1与3-取代苯甲叉基-2,4-戊二酮 2以碳酸钾为碱,在苯中55℃条件下反应,可以较好的收率、高立体选择性地生成反-2-(a-噻吩甲酰基)-3-取代苯基-4-乙氧羰基-5-甲基-2,3-二氢呋喃3。产物结构均经波谱予以确定。本文还提出了生成产物的可能机理。     

One‐Pot Synthesis of 4‐(2,3‐Dihydro‐2‐hydroxy‐1,3‐dioxo‐1H‐inden‐2‐yl)‐Substituted 1‐Aryl‐1H‐pyrazole‐3‐carboxylates via a Tandem Three‐Component Reaction

The hitherto unreported, highly functionalized 1H‐pyrazole‐3‐carboxylates 3 have been synthesized in good yields via a one‐pot three‐component domino reaction of phenylhydrazines, dialkyl acetylenedicarboxylates, and ninhydrin under mild conditions for the first time. No co‐catalyst or activator is required for this multicomponent reaction, and the reaction is, from an experimental point of view, simple to perform (Scheme 1). The structures of compounds 3 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization/addition reaction is proposed (Scheme 2).     

Experimental and Theoretical Studies of Bromination of Diethyl 2,4,6‐Trimethyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate

A reaction of diethyl 2,4,6‐trimethyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate with 1, 2, and more equivalents of N‐bromosuccinimide (NBS) in methanol was investigated by NMR spectroscopy at a temperature interval ranging from 25 to 40°C. The reaction was found to proceed through several steps. The structures of the intermediates diethyl 3‐bromo‐2,4,6‐trimethyl‐3,4‐dihydropyridine‐3,5‐dicarboxylate, diethyl 3‐bromo‐2‐methoxy‐2,4,6‐trimethyl‐1,2,3,4‐tetrahydropyridine‐3,5‐dicarboxylate, and diethyl 3,5‐dibromo‐2‐methoxy‐2,4,6‐trimethyl‐2,3,4,5‐tetrahydropyridine‐3,5‐dicarboxylate were identified by multinuclear (¹H, ¹³C, and ¹⁵N) NMR spectral data. The optimal structures of all species participating in the reaction as well as changes in their relative energies along with the proposed pathway of the reaction were analyzed by quantum‐chemical calculations. The mechanism of bromination of diethyl 2,4,6‐trimethyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate with NBS in methanol was found to favor the bromination in the 2,6‐methyl side chains as the only products in full agreement with experimental observations.     

One‐pot,Three‐component Synthesis of a New Series of 2‐Amino‐4‐aroyl‐5‐oxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carbonitrile in the Presence of SBA‐15 as a Nanocatalyst

One‐pot, three‐component reaction of arylglyoxals, malononitrile and 4‐hydroxyquinolin‐2(1H)‐one in the presence of SBA‐15 as a nanocatalyst and using green solvent systems under various temperatures afforded the 2‐amino‐4‐aroyl‐5‐oxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carbonitrile derivatives. The best yield (70‐96%) were obtained using 20% mol of SBA‐15 as a nanocatalyst in H2O/EtOH (1:1) at 80 °C. The simplicity of work up procedure, using green solvent system, and good to excellent yields of products are the main advantages of this synthetic strategy.     

Efficient One‐Pot Synthesis of Alkyl 2‐(Dialkylamino)‐4‐phenylthiazole‐5‐carboxylates and Single‐Crystal X‐Ray Structure of Methyl 2‐(Diisopropylamino)‐4‐phenylthiazole‐5‐carboxylate

The reaction between secondary amines, benzoyl isothiocyanate, and dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) in the presence of silica gel (SiO₂) led to alkyl 2‐(dialkylamino)‐4‐phenylthiazole‐5‐carboxylates in fairly high yields. The structures of the products were confirmed by their IR, ¹H‐ and ¹³C‐NMR, and mass spectra, and by a single‐crystal X‐ray structure determination.     

An Efficient Synthesis of 1′,7′,8′,9′‐Tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione Derivatives in Aqueous Medium

An efficient and green reactions of isatins, 3‐amine‐1H‐pyrazole (5‐methyl‐1H‐pyrazol‐3‐amine) and 1,3‐diketone in aqueous medium for the synthesis of novel 1′,7′,8′,9′‐tetrahydrospiro[indoline‐3,4′‐pyrazolo[3,4‐b]quinoline]‐2,5′(6′H)‐dione derivatives were reported in this research. The advantages of this reaction are simple operation, mild‐reaction conditions, wide scope substrate, high yields, and friendly environment. The products were confirmed by IR, ¹H NMR, ¹³C NMR, and HRMS.     

Synthesis of Novel 6‐Mercapto‐12‐phenethyl‐quinazolino[3,4‐a]quinazolinones

Novel 6‐mercapto‐12‐phenethyl‐quinazolino[3,4‐a]quinazolinone derivatives were synthesized through a user‐friendly five‐step reaction starting from isatoic anhydride. All products were characterized by IR, ¹H‐NMR, ¹³C‐NMR spectroscopy, and chemical analysis. All of them were evaluated for their in vitro cytotoxic activity against two cell lines namely MOLT‐4 (human lymphoblastic leukemia) and MCF‐7 (human breast adenocarcinoma).     

Unexpected Spiroproducts from the Reaction of N‐Benzoylglycine with Ortho‐Formylbenzoic Acids −3,5′‐Dioxo‐2′‐Phenyl‐1,3‐Dihydrospiro[Indene‐2,4′‐[1,3]Oxazol]‐1‐yl Acetates: Establishments of Their Structure

This paper describes a method of preparation of new 3,5′‐dioxo‐2′‐phenyl‐1,3‐dihydrospiro[indene‐2,4′‐[1,3]oxazol]‐1‐yl acetate and its 5‐chloro‐ and bromoderivatives as products of interaction of N‐benzoylglycine (hippuric acid) with corresponding ortho‐formylbenzoic acids. The reaction carried out in acetic anhydride media in the presence of piperidine as catalyst. The novel spirocompounds were purified by column chromatography from multicomponent reaction mixtures. The composition of the spiro‐products was confirmed by C, H, N element analysis. The structure was established by IR, MS, ¹H‐ and ¹³C‐NMR analysis including COSY ¹H‐¹³C experiments.     

Ultrasound‐Assisted Synthesis of 6‐Methyl‐1,2,3,4‐tetrahydro‐N‐aryl‐2‐oxo/thio‐4‐arylpyrimidine‐5‐carboxamides Catalyzed by Uranyl Nitrate Hexahydrate

An efficient and simple method developed for the synthesis of 6‐methyl‐1,2,3,4‐tetrahydro‐N‐aryl‐2‐oxo/thio‐4‐arylpyrimidine‐5‐carboxamide derivatives ( 4a‐o ) using UO₂(NO₃)₂.6H₂O catalyst under conventional and ultrasonic conditions. The ultrasound irradiation synthesis had shown several advantages such as milder conditions, shorter reaction times and higher yields. The structures of all the newly synthesized compounds have been confirmed by FT‐IR, ¹H NMR, ¹³C NMR and mass spectra.     

One‐Pot Synthesis of 4‐(Alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐ dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones via a Multicomponent Reaction

An effective route to novel 4‐(alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones 10 is described (Scheme 2). This involves the reaction of an enamine, derived from the addition of a primary amine 5 to 1,4‐diphenylbut‐2‐yne‐1,4‐dione, with an arenesulfonyl isocyanate 7 . Some of these pyrrolones 10 exhibit a dynamic NMR behavior in solution because of restricted rotation around the C? N bond resulting from conjugation of the side‐chain N‐atom with the adjacent α,β‐unsaturated ketone group, and two rotamers are in equilibrium with each other in solution ( 10 ? 11 ; Scheme 3). The structures of the highly functionalized compounds 10 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS), by elemental analyses, and, in the case of 10a , by X‐ray crystallography. A plausible mechanism for the reaction is proposed (Scheme 4).     

Synthesis and Antimicrobial Activity of 2‐(4‐(Hydroxyalkyl)‐1H‐1,2,3‐triazol‐1‐yl)‐N‐substituted propanamides

A series of 21 2‐(4‐(hydroxyalkyl)‐1H ‐1,2,3‐triazol‐1‐yl)‐N ‐substituted propanamides (1,4‐disubstituted 1,2,3‐triazoles having amide linkage and hydroxyl group) have been synthesized from click reaction between terminal alkyne and 2‐azido‐N ‐substituted propanamide (generated in situ from reaction of 2‐bromo‐N ‐substituted propanamide and sodium azide) and characterized by FTIR, ¹H NMR, ¹³C NMR spectroscopy, and HRMS. All the newly synthesized triazoles were tested in vitro for antimicrobial activity against four bacterial cultures – Escherichia coli , Enterobacter aerogenes , Klebsiella pneumoniae , and Staphylococcus aureus – and two fungal cultures – Candida albicans and Aspergillus niger . The synthesized 1,4‐disubstituted 1,2,3‐triazoles displayed moderate to good antimicrobial potential against the tested strains.     

固相β-环糊精包结物诱导7-羟基-2-甲氧基-2-甲基色满的不对称合成

研究了室温下间苯二酚和甲基乙烯基酮分别与β-环糊精（ β-CD）形成包结物后的几种不同固相反应,结果表明包结物A（间苯二酚/β-CD）与包结物B（甲基乙烯基酮/β-CD）反应能够很好地得到目的产物,产率及ee值分别为82.8%和78.4%;间苯二酚与包结物B反应仅得到低光学活性产物（ee值为19.5%）;包结物A与甲基乙烯基酮反应却没有得到手性目的产物。以熔点、X-粉末衍射、固相核磁碳谱及ROESY多种方法对所形成的包结物进行了表征,包结物中主客体的比例（1：1）通过¹H NMR (400 MHz)得以确定,文章对固相环加成反应的机制也进行了初步探讨。     

Efficient Synthesis of 2,3‐Disubstituted‐1,3‐benzoxazines by Chlorotrimethylsilane‐Mediated Aza‐Acetalizations of Aromatic Aldehydes

A series of novel substituted 3,4‐dihydro‐2H‐1,3‐benzoxazines were prepared in moderate to good yields by aza‐acetalizations of aromatic aldehydes with 2‐(N‐substituted aminomethyl)phenols in the presence of chlorotrimethylsilane or SnCl₄. It was found that chlorotrimethylsilane was more effective for the reaction, especially for the reaction of fluorobenzaldehyde, and thereby, an efficient method for the preparation of 3,4‐dihydro‐2H‐1,3‐benzoxazines was developed. The structures of the compounds were determined by FT‐IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis.     

Preparation of 2‐phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline and 2‐methyl‐4‐oxo‐3,4‐dihydroquinazoline derivatives formation

The cyclization of phenacyl anthranilate has been studied with the aim to develop the synthesis of 2‐(2′‐aminophenyl)‐4‐phenyloxazole. However, a different course of the reaction than expected was observed. 2‐Phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 3a ) was formed by the reaction of phenacyl anthranilate ( 2 ) with ammonium acetate under various conditions. 3‐Hydroxy‐2‐phenyl‐4(1H)‐quinolinone ( 4 ) arose by heating compound 3a in acetic acid. The same compound was obtained by melting compound 3a , but the yield was lower. Different types of products resulted in the reaction of compound 3a with acetic anhydride. Under mild conditions acetylated products 2‐acetoxymethyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 7a ) and 2‐acetoxymethyl‐3‐acetyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 8 ) were prepared. If the reaction was carried out under reflux of the reaction mixture, molecular rearrangement took place to give cis and trans 2‐methyl‐4‐oxo‐3‐(1‐phenyl‐2‐acetoxy)vinyl‐3,4‐dihydroquinazolines ( 9a and 9b ). All prepared compounds have been characterised by their ¹H, ¹³C and ¹⁵N NMR spectra, IR spectra and MS.     

Synthesis of New 1,2,3‐Triazole Derivatives Possessing 4H‐Pyran‐4‐one Moiety by 1,3‐Dipolar Cycloaddition Reaction of Azidomethyl Phenylpyrone with Various Alkynes

A series of new 1,2,3‐triazole derivatives were synthesized by 1,3‐dipolar cycloaddition reaction of 2‐(4‐azidomethylphenyl)‐6‐phenyl‐4H‐pyran‐4‐one with different alkynes in 40–71% yields. In the case of terminal alkynes, the reaction was proceeded in the presence of Cu(I) catalyst. The structure of the synthesized compounds were confirmed by FTIR, ¹H‐NMR, and ¹³C‐NMR spectroscopy and elemental analysis.