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).     

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。     

Hydriodic Acid‐Mediated Cyclization of α‐Substituted Secondary 2‐Ethenylbenzamides: Synthesis of 2‐Substituted 2,3‐Dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones and 3,3‐Disubstituted (E)‐1‐(Arylimino)‐1,3‐dihydroisobenzofurans

A new and facile method for the preparation of 2‐substituted 2,3‐dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones 3 and 3,3‐disubstituted (E)‐1‐(arylimino)‐1,3‐dihydroisobenzofurans 6 has been developed. Thus, treatment of N‐alkyl(or aryl)‐2‐(1‐methylethen‐1‐yl)benzamides 2 with concentrated hydriodic acid (HI) in MeCN at room temperature afforded 3 . Similar treatment of N‐aryl‐2‐(1‐phenylethen‐1‐yl)benzamide 5 with concentrated HI at 0° afforded 6 .     

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 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 .     

One‐Pot Four‐Component Synthesis of N2‐Alkyl‐N3‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines

A simple synthesis of N²‐alkyl‐N³‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines 5 via a one‐pot four‐component reaction is described (Scheme 1). A mixture of N‐(isocyanoimino)triphenylphosphorane ( 1 ), a 2‐aminobenzoic acid 2 , a 2‐hydroxybenzaldehyde 3 , and an isocyanide 4 in absolute EtOH at room temperature undergoes a smooth reaction to afford 5 in excellent yields (Table).     

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.     

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.     

Isocyanide‐Based Three‐Component Synthesis of Highly Substituted 1,6‐Dihydro‐6,6‐dimethylpyrazine‐2,3‐dicarbonitrile, 3,4‐Dihydrobenzo[g]quinoxalin‐2‐amine,and 3,4‐Dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine Derivatives

A novel and efficient isocyanide‐based multicomponent reaction between alkyl or aryl isocyanides 1 , 2,3‐diaminomaleonitrile ( 2 ), naphthalene‐2,3‐diamines ( 6 ) or benzene‐1,2‐diamine ( 9 ), and 3‐oxopentanedioic acid ( 3 ) or Meldrum's acid ( 4 ) or ketones 7 was developed for the ecologic synthesis, at room temperature under mild conditions, of 1,6‐dihydropyrazine‐2,3‐dicarbonitriles 5a – 5f in H₂O without using any catalyst, and of 3,4‐dihydrobenzo[g]quinoxalin‐2‐amine and 3,4‐dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine derivatives 8a – 8g and 10a – 10e , respectively, in the presence of a catalytic amount of p‐toluenesulfonic acid (TsOH) in EtOH, in good to excellent yields (Scheme 1).     

Preparation of 8‐Aza‐7‐deazaaristeromycin and ‐neplanocin A and Their 5′‐Homologs

The synthesis of new members of the aristeromycin and neplaoncin A families of carbocyclic nucleosides possessing the 1H‐pyrazolo[3,4‐d]pyrimidine ring is reported. For this purpose, an adapted route to 4‐amino‐1H‐pyrazolo[3,4‐d]pyrimidine is described.     

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 and Structure of O,O‐Diethyl N‐[(trans‐4‐Aryl‐5,5‐dimethyl‐2‐oxido‐2λ5‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates

A study on the synthesis of the novel N‐(cyclic phosphonate)‐substituted phosphoramidothioates, i.e., O,O‐diethyl N‐[(trans‐4‐aryl‐5,5‐dimethyl‐2‐oxido‐2λ⁵‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates 4a – l , from O,O‐diethyl phosphoramidothioate ( 1 ), a benzaldehyde or ketone 2 , and a 1,3,2‐dioxaphosphorinane 2‐oxide 3 was carried out (Scheme 1 and Table 1). Some of their stereoisomers were isolated, and their structure was established. The presence of acetyl chloride was essential for this reaction and accelerated the process of intramolecular dehydration of intermediate 5 forming the corresponding Schiff base 7 (Scheme 2).     

Microwave‐induced Stereoselectivity in Synthesis of trans‐4‐Aryl‐3‐methyl‐6‐oxo‐4,5,6,7‐tetrahydro‐2H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

A facile synthesis of trans isomers of 4‐aryl‐3‐methyl‐6‐oxo‐4,5,6,7‐tetrahydro ‐ 2H ‐ pyrazolo[3,4‐b]pyridine‐5‐carbonitriles via three‐component condensation reaction of an aldehyde, 3‐amino‐5‐methylpyrazole and ethyl cyanoacetate in acetonitrile has been developed under microwave irradiation. This one‐pot reaction proceeds without any catalyst in short times and gives the product in high selectivities and high yields.     

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).     

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.     

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.     

Ultrasound‐Assisted Synthesis of 3‐(Arylamino)‐1‐ferrocenylpropan‐1‐ones

A successful aza‐Michael addition of arylamines to a conjugated enone, acryloylferrocene, has been achieved by ultrasonic irradiation of the mixture of these reactants and the catalyst, i.e., montmorillonite K‐10. This solvent‐free reaction, yielding ferrocene containing Mannich bases, 3‐(arylamino)‐1‐ferrocenylpropan‐1‐ones, considered as valuable precursors in organic synthesis, has been performed by using a simple ultrasonic cleaner. Among 17 synthesized β‐amino ketones, three were new ones, and these were fully characterized by spectroscopic means. X‐Ray crystallographic analysis of three of these crystalline products enabled the insight into the conformational details of these compounds. All compounds were evaluated for their antibacterial activities against six Gram‐positive and five Gram‐negative strains in a microdilution assay. The observed promising antibacterial activity (with a MIC value of 25 μg/ml (ca. 0.07 μmol/ml) as the best result for almost all tested compounds against Micrococcus flavus) seems not only to be compound but also bacterial species‐specific.     

Synthesis of 2‐Mercaptobenzaldehyde, 2‐Mercaptocyclohex‐1‐enecarboxaldehydes and 3‐Mercaptoacrylaldehydes

A novel one‐pot approach for the preparation of 2‐mercaptobenzaldehyde, 2‐mercaptocyclohex‐1‐enecarboxaldehydes and 3‐mercaptoacrylaldehydes [(Z)‐3‐mercapto‐2‐methyl‐3‐phenylacrylaldehyde, 3‐mercapto‐3‐(o‐tolyl)acrylaldehyde)] starting from ortho‐bromobenzaldehyde, 2‐chlorocyclohex‐1‐enecarbaldehydes, (Z)‐3‐chloro‐2‐methyl‐3‐phenylacrylaldehyde and 3‐chloro‐3‐(o‐tolyl)acrylaldehyde is reported. The reaction of sulfur with the Grignard reagent of the acetal for the protection of the aldehyde group affords the title compounds through hydrolysis with dilute hydrochloric acid in high yields.     

Synthesis of 4‐Aryl‐3‐Methyl‐1‐Phenyl‐1H‐Benzo[h]Pyrazolo[3,4‐b]Quinoline‐5,10‐diones Using Diammonium Hydrogen Phosphate as an Efficient and Versatile Catalyst in Water

A simple and efficient synthesis of 4‐aryl‐3‐methyl‐1‐phenyl‐1H‐benzo[h]pyrazolo[3,4‐b]quinoline‐5,10‐diones has been accomplished by the one‐pot condensation reaction of 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine, aldehydes and 2‐hydroxynaphthalene‐1,4‐dione in water in the presence of diammonium hydrogen phosphate.     

Facile Synthesis of 5‐Hexyl‐4‐methyl‐γ‐butyrolactone via Nef Reaction as a Key Step

A racemic cis/trans mixture of 5‐hexyl‐4‐methyl‐γ‐butyrolactone was easily synthesized from 1‐iodoheptane in four steps with inexpensive and readily available reagents. Our new synthesis method can be potentially employed for mass production of the 4‐methyl‐5‐hexyl‐γ‐butyrolactone as well as other poly‐alkyl substituted γ‐butyrolactones.