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.     

A simple synthesis of 5‐ethoxycarbonyl‐6‐phenyl‐1,3‐dioxin‐4‐ones and ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate

4‐Ethoxycarbonyl‐5‐phenyl‐2,3‐dihydrofuran‐2,3‐dione 1 reacts with aldehydes via the acylketene intermediate 2 giving the 1,3‐dioxin‐4‐ones 3a‐e and the 1,4‐bis(5‐ethoxycarbonyl‐4‐oxo‐6‐phenyl‐4H‐1,3‐dioxin‐2‐yl)benzene 4 , and a one step reaction between dibenzoylmethane and oxalylchloride gave 3,5‐dibenzoyl‐2,6‐diphenyl‐4‐pyrone 7 . The reaction of 1 with dibenzoylmethane, a dicarbonyl compound, provided ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate derivative 9 . Compound 9 was converted into the corresponding ethyl 3‐benzoyl‐4‐hydroxy‐2,6‐diphenylpyridine‐5‐carboxylate derivative 10 via its reaction with ammonium hydroxyde solution in 1 ‐butanol.     

Novel synthesis of 3‐phenylazo‐1,5‐benzothiazepines, ‐1,5‐benzoxazepines and ‐1,5‐benzodiazepines via a one‐pot reaction

Novel polysubstituted ‐1,5‐benzothiazepine, ‐1,5‐benzoxazepine, and ‐1,5‐benzodiazepine were prepared in good yields by the reaction of hydrazono derivatives with o‐thioaminophenol, o‐aminophenol and o‐phenylenediamine via a one‐pot reaction.     

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.     

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).     

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.     

An Efficient Synthesis of 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐6‐methyl‐4‐(2‐oxo‐2‐phenylethoxy)‐3,4‐dihydro‐2H‐pyran‐2‐one Derivatives via Multi‐Component Approach

An easy, highly efficient and a new convenient one‐pot, two‐step approach to the synthesis of 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐6‐methyl‐4‐(2‐oxo‐2‐phenylethoxy)‐3,4‐dihydro‐2H‐pyran‐2‐one is described. These compounds were synthesized from 3‐(3‐benzyl‐2‐(phenylimino)‐2,3‐dihydrothiazol‐4‐yl)‐4‐hydroxy‐6‐methyl‐3,4‐dihydro‐2H‐pyran‐2‐one and α‐bromoketones in good yields. The compounds 4 were synthesized by a multi‐component reaction between 1 , 2 , and 3 and the prominent features of this protocol are mild reaction conditions, operation simplicity, and good to high yields of products.     

New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine

The model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N⁴‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N⁴‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline ( 5 ) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine ( 8 ) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. ¹H nmr, ¹³C nmr, ir, mass spectroscopy and x‐ray identified compounds ( 4 ), ( 5 ) and ( 8 ).     

Heterocyclization reaction of 2‐(2‐methylaziridin‐1‐yl)‐3‐ureidopyridines under appel's conditions

The reaction of 2‐(2‐methylaziridin‐1‐yl)‐3‐ureidopyridines 12 with triphenylphosphine, carbon tetra‐chloride, and triethylamine (Appel's conditions) led to the corresponding carbodiimides 13 , which underwent intramolecular cycloaddition reaction with aziridine under the reaction conditions to give the pyridine‐fused heterocycles, 2,3‐dihydro‐1H‐imidazo[2′,3′:2,3]imidazo[4,5‐b]pyridines 16 and 12,13‐dihydro‐5H‐1,3 ‐benzodiazepino [2′,3′:2,3] imidazo[4,5‐b]pyridines 17 .     

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.     

4‐hydroxy‐6‐methyl‐3‐(5‐phenyl‐2E,4E‐pentadien‐1‐oyl)‐2H‐pyran‐2‐one: Synthesis and reactivity with amines

The synthesis and reactivity studies of 4‐hydroxy‐6‐methyl‐3‐(5‐phenyl‐2E,4E‐pentadien‐1‐oyl)‐2H‐pyran‐2‐one 2 with nucleophiles are reported. Reactions of 2 with hydrazine derivatives gave new pyrazole‐type com pounds while the reaction with ortho‐phenylenediamines yielded 1,5‐benzodiazepines. The reaction of 2 with ethylamine implies the 2H‐pyran‐2‐one ring opening and the formation of a strong conjugated compound 3.     

Synthesis of Some New Heterocycles Derived from Ethyl 7‐Amino‐3‐(3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazolin‐4‐yl)‐5‐aryl‐5H‐thiazolo[3,2‐a]pyrimidine‐6‐carboxylate of Biological Importance

Ethyl 7‐amino‐3‐(3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazolin‐4‐yl)‐5‐aryl‐5H‐thiazolo[3,2‐a]pyrimidine‐6‐carboxylate was synthesized by the reaction of 4‐(2‐aminothiazol‐4‐yl)‐3‐methyl‐5‐oxo‐1‐phenyl‐2‐pyrazoline with arylidene ethyl cyanoacetate and it transformed to related fused heterocyclic systems via reaction with various reagents. The biological activities of these compounds were evaluated.     

New trans/cis tetrahydroisoquinolines. 2. trans‐ and cis‐3‐(1‐methyl‐1h‐pyrrol‐2‐yl)‐1‐(2H)‐oxo‐2‐phenethyl‐1,2,3,4‐tetrahydroisoquino‐lin‐4‐carboxylic acids and subsequent transformations

Stereochemical course of the reaction of homophthalic anhydride and N‐(1‐methyl‐1H‐pyrrol‐2‐yl‐methylidene)‐phenethylamine was studied. Mixtures of the expected trans‐ and cis‐1,2,3,4‐tetrahydroiso‐quinoline‐4‐carboxylic acids trans‐ 4 and cis‐ 4 were obtained along with by‐products 5 and 6 . The ratios of all products and the diastereomers, obtained under different reaction conditions, were established by pmr. THF as a solvent and ultrasonic treatment are applied for the first time in the reaction of this type. The reaction was made diastereoselective towards any isomer. The carboxylic group of trans‐ 4 was transformed in four steps into various cyclic amino‐methyl groups yielding numerous new tetrahydroisoquinolinones trans‐ 10a‐i incorporating a given fragment of pharmacological interest. Reduction of 10a‐i was studied.     

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。     

Quinolone analogues 1. A convenient synthesis of 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxaline‐3‐carboxylic acids

The reaction of the alkylhydrazinoquinoxaline N‐oxides 2a‐d with dimethyl acetylenedicarboxylate gave the dimethyl 1‐alkyl‐1,5‐dihydropyridazino[3,4‐b]qumoxaline‐3,4‐dicarboxylates 3a‐d , whose reaction with nitrous acid effected the C₄‐oxidation to afford the dimethyl 1‐alkyl‐4‐hydroxy‐1,4‐dihydropyridazino‐[3,4‐b]quinoxaline‐3,4‐dicarboxylates 4a‐d , respectively. The reaction of compounds 4a‐d with 1,8‐diazabicyclo[5.4.0]‐7‐undecene in ethanol provided the ethyl 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxa‐line‐3‐carboxylates 5a‐d , while the reaction of compounds 4a‐d with potassium hydroxide furnished the 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxaline‐3‐carboxylic acids 6a‐d , respectively. Compounds 6c,d were also obtained by the reaction of compounds 5c,d with potassium hydroxide, respectively.     

An Innovative Protocol for the Synthesis of 3‐(Pyridin‐2‐yl)‐5‐sec‐aminobiphenyl‐4‐carbonitriles and 9,10‐Dihydro‐3‐(pyridine‐2‐yl)‐1‐sec‐aminophenanthrene‐2‐carbonitriles

Herein, we present an innovative, novel, and highly convenient protocol for the synthesis of 3‐(pyridin‐2‐yl)‐5‐sec‐aminobiphenyl‐4‐carbonitriles ( 6a , 6b , 6c , 6d , 6e , 6f , 6g ) and 9,10‐dihydro‐3‐(pyridine‐2‐yl)‐1‐sec‐aminophenanthrene‐2‐carbonitriles ( 10a , 10b , 10c , 10d , 10e ), which have been delineated from the reaction of 4‐sec‐amino‐2‐oxo‐6‐aryl‐2H‐pyran‐3‐carbonitrile ( 4a , 4b , 4c , 4d , 4e , 4f , 4g ) and 4‐sec‐amino‐2‐oxo‐5,6‐dihydro‐2H‐benzo[h]chromene‐3‐carbonitriles ( 9a , 9b , 9c , 9d , 9e ) with 2‐acetylpyridine ( 5 ) through the ring transformation reaction by using KOH/DMF system at RT. The salient feature of this procedure is to provide a transition metal‐free route for the synthesis of asymmetrical 1,3‐teraryls like 3‐(pyridin‐2‐yl)‐5‐sec‐aminobiphenyl‐4‐carbonitriles ( 6a , 6b , 6c , 6d , 6e , 6f , 6g ) and 9,10‐dihydro‐3‐(pyridine‐2‐yl)‐1‐sec‐aminophenanthrene‐2‐carbonitriles ( 10a , 10b , 10c , 10d , 10e ). The novelty of the reaction lies in the creation of an aromatic ring from 2H‐pyran‐2‐ones and 2H‐benzo[h]chromene‐3‐carbonitriles via two‐carbon insertion from 2‐acetylpyridine ( 5 ) used as a source of carbanion.     

Quinolone analogues 6 [1‐5]. Synthesis of 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b , whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d , whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d , respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d , whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐d , respectively. Compounds 6a‐d had antifungal activities in vitro.     

A Concise Synthesis of 2‐Amino‐1,2,3,4‐tetrahydronaphthalene‐6,7‐diol (‘6,7‐ADTN’) from Naphthalene‐2,3‐diol

2‐Amino‐1,2,3,4‐tetrahydronaphthalene‐6,7‐diol ( 2 ; 6,7‐ADTN) was synthesized starting from naphthalene‐2,3‐diol in seven steps and with an overall yield of 44%. Methylation of naphthalene‐2,3‐diol with dimethyl sulfate, followed by Friedel? Crafts acylation with AcCl, gave 2‐acetyl‐6,7‐dimethoxynaphthalene. 2‐Acetyl‐6,7‐dimethoxynaphthalene was converted to 6,7‐dimethoxynaphthalene‐2‐carboxylic acid by a haloform reaction. Birch reduction of the carboxylic acid with 4 mol‐equiv. of Na in liquid ammonia afforded 1,2,3,4‐tetrahydro‐6,7‐dimethoxynaphthalene‐2‐carboxylic acid, from which 2 was obtained by a Curtius reaction, followed by hydrogenolysis and demethylation.     

An Efficient and Facile Synthesis of tert‐Butyl 2‐(Methylamino)‐3‐nitro‐5‐oxo‐4‐aryl‐7,8‐dihydro‐4H‐pyrano[3,2‐c]pyridine‐6(5H)‐carboxylate derivatives in [BMIM]BF4

In this research, we have developed an efficient three‐component reaction for the synthesis of pyrano[3,2‐c]pyridine derivatives from the reaction of aromatic aldehydes, tert‐butyl 2,4‐dioxopiperidine‐1‐carboxylate, and N‐methyl‐1‐(methylthio)‐2‐nitroethylen‐1‐amine in [BMIM]BF₄ medium. The advantages of this method were readily available starting materials, simple reaction conditions, and satisfactory yields.     

Synthesis and antimicrobial activity of 3‐(N‐arylamino)‐2‐phenyl‐naphtho[1,3‐d]‐1,2‐oxaphosphole 2‐oxides

The efficient preparation of cis‐3‐(N‐arylamino)‐2‐phenylnaphtho[1,3‐d]‐1,2‐oxaphosphole 2‐oxides 4 and 5 is described by a three‐component reaction involving phenyldichlorophosphine ( 2 ) 1‐hydroxy‐2‐naph‐thaldehyde/1‐hydroxy‐2‐acetonaphthone ( 1 ) and different substituted amines ( 3 ) in anhydrous benzene. The stereo structure, of the products ( 4 and 5 ), as well as the reaction mechanism of the cyclization is discussed. The title compounds ( 4 and 5 ) were fully characterized by NMR and mass spectral data. Their anti microbial activity was evaluated