Synthesis of 3‐Aryl‐2‐methoxyinden‐1‐one (Z)‐Phenylhydrazones via Hydrobromic Acid‐Mediated Cyclization of 2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehyde Phenylhydrazones

2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes 2 , obtained by successive treatment of 1‐(1‐aryl‐2‐methoxyethenyl)‐2‐bromobenzenes 1 with BuLi and 1‐formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH₂. When these hydrazones were allowed to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3‐aryl‐2‐methoxyinden‐1‐one (Z)‐phenylhydrazones 4 .     

Synthesis of 4‐Arylisocoumarins (=4‐Aryl‐1H‐2‐benzopyran‐1‐ones) through Acidic Hydrolysis of (Z)‐2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes,Followed by Oxidation

4‐Arylisocoumarins (=4‐aryl‐1H‐2‐benzopyran‐1‐ones) 6 were prepared from 2‐(1‐aryl‐2‐methoxyethenyl)‐1‐bromobenzenes 1 . Successive treatment of these bromo styrenes with BuLi and 1‐formylpiperidine gave a mixture of (E)‐ and (Z)‐2‐(1‐aryl‐2‐methoxyethenyl)benzaldehydes 2 . Hydrolysis of (Z)‐isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1H‐2‐benzopyran‐1‐ol derivatives 4 (and 5 ), afforded the desired products.     

Synthesis of (4Z)‐4‐(Arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones by the Reaction of Ethyl (2Z)‐3‐Aryl‐2‐isothiocyanatoprop‐2‐enoates with Organolithium Compounds

A convenient one‐pot method for the preparation of (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones 2 and 3 from ethyl (2Z)‐3‐aryl‐2‐isothiocyanatoprop‐2‐enoates 1 , which can be easily prepared from ethyl 2‐azidoacetate and aromatic aldehydes, has been developed. Thus, these α‐isothiocyanato α,β‐unsaturated esters were treated with organolithium compounds, including lithium enolates of acetates, to provide 5‐substituted (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones, 2 , and 2‐[(4Z)‐(4‐arylmethylidene)‐5‐ethoxy‐2‐thioxo‐1,3‐oxazolidin‐5‐yl]acetates, 3 .     

Design,Synthesis, Antifungal Activities and SARs of (R)‐2‐Aryl‐4,5‐dihydrothiazole‐4‐carboxylic Acid Derivatives

Based on the structure of natural product 2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid, a series of novel (R)‐2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The single crystal structure of compound 9b was determined by X‐ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a (against Cercospora arachidicola Hori), 13d (against Alternaria solani), and 16e (against Cercospora arachidicola Hori) were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested (66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 µg?mL). Therefore, 13d can be used as a new lead structure for the development of antifungal agents.     

HClO4‐SiO2: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

HClO₄‐SiO₂, efficiently catalyzed the condensation of o‐aminophenols and 2‐bromo‐1‐aryl‐ethanones to yield 3‐aryl‐2H‐benzo[1,4]oxazines in good yields.     

Reaction of 3‐Hydroxyquinoline‐2,4‐diones with Inorganic Thiocyanates in the Presence of Ammonium or Alkylammonium Ions: the Unexpected Replacement of a Hydroxy Group by an Amino Group

3‐Hydroxyquinoline‐2,4‐diones react with KSCN in the presence of the NH$\rm{{_{4}^{+}}}$ ions to generate 2,3‐dihydro‐3‐thioxoimidazo[1,5‐c]quinazolin‐5(6H)‐ones, 2,3‐dihydro‐2‐thioxo‐1H‐imidazo[4,5‐c]quinolin‐4(5H)‐ones, and products of molecular rearrangement of the 3‐aminoquinolinedione intermediates. Starting compounds with a benzyl (Bn) group at C(3) afford 3‐aminoquinolinediones, even when only AcONH₄ is used. The results of the reaction between 3‐hydroxyquinoline‐2,4‐diones and KSCN in the presence of BuNH₂ show that replacing a OH group with a secondary NH₂ group is also possible.     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

Synthesis of 10‐Aryl‐ and 10‐(Arylmethyl)acridin‐9(10H)‐ones via the Reaction of (2‐Fluorophenyl)(2‐halophenyl)methanones with Benzenamines and Arylmethanamines

The reaction of 1‐fluoro‐2‐lithiobenzenes, generated from 1‐bromo‐2‐fluorobenzenes 1 and BuLi, with 2‐halobenzaldehydes and subsequent oxidation of the resulting alcohols 2 afforded (2‐fluorophenyl)(2‐halophenyl)methanones 3 , which, on treatment with benzenamines or arylmethanamines, followed by NaH, gave rise efficiently to 10‐aryl‐ or 10‐(arylmethyl)acridin‐9(10H)‐ones ( 5 or 7 ), respectively.     

Synthesis of Isoindolo[2,1‐a]quinazoline‐5,11‐dione Derivatives via the Reductive One‐Pot Reaction of N‐Substituted 2‐Nitrobenzamides and 2‐Formylbenzoic Acids

Various isoindolo[2,1‐a]quinazoline‐5,11‐dione derivatives 3 were synthesized in good yields by means of the reductive reaction of N‐substituted 2‐nitrobenzamides 1 and 2‐formylbenzoic acids 2 in the presence of SnCl₂?2 H₂O under reflux in EtOH (Scheme, Table). The procedure needed two steps, the reduction of the nitro group of the 2‐nitrobenzamide and ring closure by nucleophilic addition of the NH₂ group to both the formyl and carboxylic acid C?O groups.     

The Stereoselective Synthesis of 2‐Aryl‐2‐hydroxybutanoic Acid via Menthyl Chiral Auxiliaries

In the presence of titanium(IV) tetraethoxide ((EtO)₄Ti), menthyl arylglyoxylates are prepared by transesterification of ethyl arylglyoxylates and natural (−)‐(1R,2S,5R)‐menthol. Using menthyl as a chiral auxiliary, the corresponding novel (R)‐menthyl 2‐aryl‐2‐hydroxybutanoates are synthesized by the addition of Et₂Zn with menthyl arylglyoxylates. The structures of the products are characterized by IR and ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, and elemental analysis. The diastereoselectivities are analyzed by HPLC. The addition reactions are completed with good yields and high diastereoisomeric excess (de up to 95%), and, after hydrolysis, the (R)‐2‐aryl‐2‐hydroxybutanoic acids are obtained with high optical purities.     

Two‐Step Synthesis of 1,3‐Disubstituted 3,4‐Dihydro‐4‐thioxoquinazolin‐2(1H)‐ones from 1‐Bromo‐2‐fluorobenzenes

An efficient synthesis of 3‐alkyl‐3,4‐dihydro‐4‐thioxobenzoquinazolin‐2(1H)‐ones 3 has been accomplished in two steps and in satisfactory yields from 1‐bromo‐2‐fluorobenzenes 1 . Thus, the reaction of 1‐fluoro‐2‐lithiobenzenes, generated by the Br/Li exchange between 1 and BuLi, with alkyl isothiocyanates, gives N‐alkyl‐2‐fluorobenzothioamides 2 , which, in turn, react with a series of isocyanates in the presence of NaH to give the desired products 3 .     

Synthesis of 2,4,8‐Trisubstituted 1,7‐Naphthyridines by the Reaction of 4‐(1‐Aryl‐2‐methoxyethenyl)‐3‐isocyanopyridines with Excess Organolithiums

A convenient method for the synthesis of 2,4,8‐trisubstituted 1,7‐naphthyridines 6 by the reaction of (E)‐4‐(1‐aryl‐2‐methoxyethenyl)‐3‐isocyanopyridines 4 , which could be easily prepared from commercially available 3‐aminopyridine via aroylation of lithium (4‐lithiopyridin‐3‐yl)pivalamide with N‐methoxy‐N‐methylbenzamides, with excess organolithiums has been developed.     

Synthesis,Characterization and Crystal Structure of Some Novel 1‐Aryl‐2‐Thioxo‐2,3‐Dihydro‐1H‐Quinazolin‐4‐Ones

The base catalyzed intramolecular nucleophilic cyclization of 1‐(2‐haloaroyl)‐3‐aryl thioureas ( 1a‐i ), in the presence of DMF afforded the 1‐aryl‐2‐thioxo‐2,3‐dihydro‐1H‐quinazolin‐4‐ones ( 2a‐i ). The structures were confirmed by spectroscopic data, elemental analyses and in case of the 2c by single crystal X‐ray diffraction data. The mechanistic studies support an intramolecular nucleophilic substitution (S_NAr mechanism) rather than intramolecular aromatic substitution (S_RN1 mechanism).     

Synthesis of 2‐Aryl‐2,3‐dihydro‐3‐sulfanyl‐1H‐isoindol‐1‐ones by Pummerer‐Type Cyclization of N‐Aryl‐2‐(sulfinylmethyl)benzamides

An efficient method for the synthesis of 2‐aryl‐2,3‐dihydro‐3‐sulfanyl‐1H‐isoindol‐1‐ones 1 via Pummerer‐type cyclization of N‐aryl‐2‐(sulfinylmethyl)benzamides 2 is described. Thus, treatment of these sulfinyl‐benzamides 2 , easily prepared from 2‐(bromomethyl)benzoates 3 in three steps, with Ac₂O at ca. 100° resulted in the formation of the desired isoindolones 1 in generally good yields.     

Liquid‐Phase Synthesis of 2‐Methyl‐2‐Aryloxypropanoic Acid Derivatives from Polyethylene Glycol) Supported 2‐Bromo‐2‐Methylpropanoate

An efficient liquid‐phase synthesis of 2‐methyl‐2‐aryloxypropanoic acid derivatives with good yields and high purity on soluble polyethylene glycol (PEG) has been developed by treatment of PEG‐bound 2‐bromo‐2‐methylpropanoate with phenoxides in the presence of a catalytic amount of NBu₄I and KI, and subsequent cleavage from the PEG.     

L-脯氨酸催化下甲基酮和1-芳基-2,2,2-三氟乙酮的不对称Aldol反应

Direct asymmetric aldol addition of methyl ketones to 2,2,2-trifluoro-1-phenylethanone and its ring-substituted derivatives was achieved using L-proline as a chiral promoter. Various optically active β-trifluoromethyl-β-hydroxy ketones were obtained in almost quantitative yields with moderate enantioselectivities up to 64 % ee.     

Synthesis of 2‐Aryl‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylates by the Reaction between Hydrazones,Acetylenedicarboxylates, and 1‐Aryl‐N,N′‐bis(arylmethylidene)methanediamines

An efficient approach for the preparation of functionalized 2‐aryl‐2,5‐dihydro‐5‐oxo‐4‐[2‐(phenylmethylidene)hydrazino]‐1H‐pyrroles is described. The four‐component reaction between aldehydes, NH₂NH₂?H₂O, dialkyl acetylenedicarboxylates, and 1‐aryl‐N,N′‐bis(arylmethylidene)methanediamines proceeds in EtOH under reflux in good‐to‐excellent yields (Scheme 1). The structures of 4 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS, and, in the case of 4f , by X‐ray crystallography). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

A Novel and Efficient One‐Pot Synthesis of 2‐Aminopyrimidinones and Their Self‐Assembly

A three‐component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium carbonate affords 2‐amino‐4‐aryl‐1,6‐dihydro‐6‐oxopyrimidine‐5‐carbonitriles and the four‐component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium hydrochloride in the presence of piperidine leads to piperidinium salts of pyrimidinones. X‐ray crystallography data confirm self‐assembly and H‐bonding in these compounds.     

Reactions with 4‐Hydroxy‐2‐methylbutananilides: Unexpected Formation of a Cyclopropanecarboxamide

The successive treatment of the N,N‐disubstituted 4‐hydroxy‐2‐methylbutanamide 2a with lithium diisopropylamide (LDA) and diphenyl phosphorochloridate (DPPCl) led to the 1‐methylcyclopropanecarboxamide 10 in good yield. This base‐catalyzed cyclization offers a new approach to cyclopropanecarboxamides. Under similar conditions, the N‐monosubstituted 4‐hydroxy‐2‐methylbutanamide 2b gave the 3‐methylpyrrolidin‐2‐one 11 . The structure of the cyclopropanecarboxamide 10 was established by X‐ray crystallography.     

A Convenient Synthesis of 2‐Sulfanylbenzoselenazole Derivatives via the Reaction of 2‐Lithiophenyl Isothiocyanates with Selenium

The title compounds have been prepared from 2‐bromophenyl isothiocyanates 1 . Thus, 2‐lithiophenyl isothiocyanates 2 , obtained from 1 and BuLi through Br/Li exchange, reacted with Se at ?78° to form lithium benzoselenazole‐2‐thiolates 3 , which, upon aqueous workup, afforded benzoselenazole‐2(3H)‐thiones 4 . The thiolates 3 were alkylated with reactive alkyl halides and acylated with carboxylic acid chlorides to give 2‐(alkylsulfanyl)benzoselenazoles 5 and S‐(benzoselenazol‐2‐yl) thiocarboxylates 6 , respectively.