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 .     

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.     

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.     

Highly efficient AgNO3‐catalyzed approach to 2‐(benzo[d]azol‐2‐yl)phenols from salicylaldehydes with 2‐aminothiophenol, 2‐aminophenol and benzene‐1,2‐diamine

A new, convenient and efficient AgNO₃‐catalyzed strategy for the preparation of 2‐(benzo[d]azol‐2‐yl)phenol derivatives in good to excellent yields (63–98%) is described. The reaction proceeds via condensation/intramolecular nucleophilic addition/oxidation process between substituted salicylaldehydes and 2‐aminothiophenol, 2‐aminophenol or benzene‐1,2‐diamine under mild reaction conditions. Notably, this reaction utilizes cheap AgNO₃ as a readily available and low‐cost benign oxidant at low catalyst loadings with excellent functional group tolerance.     

Unusual behaviour of N‐cinnamoyl‐2‐hydroxy‐2‐(trifluoromethyl)‐arylethylamines in pictet‐gams cyclization. Synthesis of 2‐styryl‐5‐aryl‐5‐trifluoromethyl‐2‐oxazolines

Cyclization of N‐acyl‐2‐hydroxy‐2‐(trifluoromethyl)arylethylamines 4 under Pictet‐Gams conditions afforded 2‐oxazolines 5 instead of the expected isoquinolines 6 . The effect of the trifluoromethyl group on the result of the reaction is discussed.     

Cross‐Linked‐Polymer‐Supported N‐{2′‐[(Arylsulfonyl)amino][1,1′‐binaphthalen]‐2‐yl}prolinamide as Organocatalyst for the Direct Aldol Intermolecular Reaction under Solvent‐Free Conditions

A bottom‐up strategy was used for the synthesis of cross‐linked copolymers containing the organocatalyst N‐{(1R)‐2′‐{[(4‐ethylphenyl)sulfonyl]amino}[1,1′‐binaphthalen]‐2‐yl}‐D ‐prolinamide derived from 2 (Scheme 1). The polymer‐bound catalyst 5b containing 1% of divinylbenzene as cross‐linker showed higher catalyst activity in the aldol reaction between cyclohexanone and 4‐nitrobenzaldehyde than 5a and 5c . Remarkably, the reaction in the presence of 5b was carried out under solvent‐free, mild conditions, achieving up to 93% ee (Table 1). The polymer‐bound catalyst 5b was recovered by filtration and re‐used up to seven times without detrimental effects on the achieved diastereo‐ and enantioselectivities (Table 2). The catalytic procedure with polymer 5b was extended to the aldol reaction under solvent‐free conditions of other ketones, including functionalized ones, and different aromatic aldehydes (Table 3). In some cases, the addition of a small amount of H₂O was required to give the best results (up to 95% ee). Under these reaction conditions, the cross‐aldol reaction between aldehydes proceeded in moderate yield and diastereo‐ and enantioselectivity (Scheme 2).     

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.     

Reactivity of 2‐Methyl‐4H‐3,1‐benzoxazin‐4‐ones and 2‐Methyl‐4H‐pyrido[2,3‐d][1,3]oxazin‐4‐one under Microwave Irradiation Conditions

The reactivity of variably substituted 2‐methyl‐4H‐3,1‐benzoxazin‐4‐ones and 2‐methyl‐4H‐pyrido[2,3‐d][1,3]oxazin‐4‐one towards carbon and oxygen nucleophiles under microwave irradiation conditions was investigated. Optimization of the reaction conditions of oxazinones with carbon nucleophiles led to the synthesis of a series of 4‐hydroxy‐quinolin‐2‐ones and 4‐hydroxy‐1,8‐naphthyridin‐2‐ones in high yields, whereas reaction with a variety of alcohols proceeded smoothly to the formation of the corresponding N‐acetyl‐anthranilates and nicotinates.     

Synthesis of Substituted α‐(Hydroxymethyl)‐β‐iodoacrylates via MgI2‐Promoted Stereoselective Aldol Coupling

The efficient and highly stereoselective syntheses of a variety of (Z)‐configured, substituted α‐(hydroxymethyl) ‐ β‐iodo‐acrylates from prop‐2‐ynoate and various aldehydes was achieved. The synthetic protocol involves a simple one‐pot coupling reaction under mild conditions, promoted by MgI₂, which serves both as a Lewis acid and iodine source for a Baylis? Hillman‐type reaction. All adducts were generated in good‐to‐excellent yields, the (Z)‐isomers being formed in high selectivity (>98%). The conversion of methyl prop‐2‐ynoate into an active ‘β‐iodo allenolate’ intermediate, which then nucleophilically attacks an aldehyde, is proposed as a plausible reaction mechanism.     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.     

Efficient Domino Approach to Polysubstituted 2‐Hydroxyindole‐3,4‐(2H,5H)‐diones

Concise and efficient domino [3 + 2] heterocyclization promoted by HCOOH has been established for unprecedented synthesis of 15 examples of 2‐hydroxyindole‐3,4‐(2H,5H)‐diones in good yields. The present methodology shows attractive properties such as mild reaction conditions, concise one‐pot operation, short reaction periods of 15–20 min, and easy purification. The resulting 2‐hydroxyindole‐3,4(2H,5H)‐diones are of importance for organic and medicinal research.     

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.     

Synthesis of Dialkyl 2‐(Alkylamino)‐4,9‐dihydro‐9‐oxocyclohepta[b]pyran‐3,4‐dicarboxylates

Dialkyl 2‐(alkylamino)‐4,9‐dihydro‐9‐oxocyclohepta[b]pyran‐3,4‐dicarboxylates are prepared in a one‐pot three‐component reaction of alkyl isocyanide, dialkyl acetylenedicarboxylate, and α‐tropolone (=2‐hydroxycyclohepta‐2,4,6‐trienone). The reaction proceeds smoothly at room temperature and under neutral conditions to afford tropolone derivatives in high yield.     

Stereoselective multicomponent synthesis of [3‐(5‐substituted 2‐methoxyphenyl)‐5‐aryl‐2‐phenyltetrahydro‐4‐isoxazolyl](2‐thienyl)methanones via 1,3‐dipolar cycloaddition

Three‐component stereoselective synthesis of a set of new tetra substituted isoxazolidines from 5‐substi‐tuted 2‐methoxybenzaldehydes, N‐phenylhydroxylamine and 1‐(2‐thienyl)‐3‐arylprop‐2‐en‐1‐ones has been achieved. The effect of microwave irradiation on the reaction under solvent‐free conditions has also been investigated. The stereochemistry of the final products has been confirmed by NMR and single crystal X‐ray analysis.     

An Efficient Synthesis of N‐Substituted‐3‐aryl‐3‐(4‐hydroxy‐6‐methyl‐2‐oxo‐2H‐pyran‐3‐yl)propanamides by Four‐Component Reaction in Aqueous Medium

A mild and efficient synthesis of N‐substituted‐3‐aryl‐3‐(4‐hydroxy‐6‐methyl‐2‐oxo‐2H‐pyran‐3‐yl)propanamides via four‐component reaction of an aldehyde, amine, Meldrum's acid, and 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one in the presence of benzyltriethylammonium chloride (TEBAC) in aqueous medium is described. This method has the advantages of accessible starting materials, good yields, mild reaction conditions, and begin environmentally friendly.     

Tandem Hydroformylation/Reductive Amination of 3‐Allyl‐2‐methylquinazolin‐4(3H)‐one

The 3‐allyl‐2‐methylquinazolin‐4(3H)‐one ( 1 ), a model functionalized terminal olefin, was submitted to hydroformylation and reductive amination under optimized reaction conditions. The catalytic carbonylation of 1 in the presence of Rh catalysts complexed with phosphorus ligands under different reaction conditions afforded a mixture of 2‐methyl‐4‐oxoquinazoline‐3(4H)‐butanal ( 2 ) and α,2‐dimethyl‐4‐oxoquinazoline‐3(4H)‐propanal ( 3 ) as products of ‘linear’ and ‘branched’ hydroformylation, respectively (Scheme 2). The hydroaminomethylation of quinazolinone 1 with arylhydrazine derivatives gave the expected mixture of [(arylhydrazinyl)alkyl]quinazolinones 5 and 6 , besides a small amount of 2 and 3 (Scheme 3). The tandem hydroformylation/reductive amination reaction of 1 with different amines gave the quinazolinone derivatives 7 – 10 . Compound 10 was used to prepare the chalcones 11a and 11b and pyrazoloquinazolinones 12a and 12b (Scheme 4).     

Microwave‐Assisted Expedite Synthesis of 2‐Phenylimidazo[1,2‐a]pyridylquinoxalin‐2(1H)‐ones

An efficient methodology has been developed for the synthesis of quinoxalin‐2(1H)‐one derivatives of 2‐phenylimidazo[1,2‐a]pyridines by microwave‐irradiated Hinsberg heterocyclization between 2‐phenylimidazo[1,2‐a]pyridine‐3‐glyoxalates and o‐phenylenediamine using either montmorillonite K‐10 or Yb(OTf)₃ as catalysts. Montmorillonite K‐10 was proven to be an efficient catalyst for the heterocyclization reaction between sterically hindered glyoxalate and o‐phenylenediamine only under microwave conditions. The use of Yb(OTf)₃/tetrahydrofuran was also found to be an effective catalyst for the above chemical transformation among a series of Lewis acids screened under microwave conditions; however, comparatively lesser yields were obtained as compared with the use of montmorillonite K‐10.     

Three‐Component One‐Pot Synthesis of 4‐Aryl‐2,3‐dihydropyrimido[1,2‐a]benzimidazol‐2‐ones Catalyzed by l‐Proline

An efficient chemoselective synthesis of 4‐aryl‐2,3‐dihydropyrimido[1,2‐a]benzimidazol‐2‐one derivatives from three‐component reactions of 2‐aminobenzimidazole, Meldrum's acid, and aldehydes via [3+3] atom combination is described. The reaction occurs in different conditions such as in DMF as solvent at reflux and in the presence of l ‐proline as base catalyst.     

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。     

Guanidinum Chloride as Dehydrocyclization Agent in the Synthesis of 2‐Fuctionalized (4H)‐3,1‐Benzoxazine‐4‐ones

A facile and expedient route for the synthesis of 2‐ethoxy‐ and 2‐(ethylcarboxylate)‐(4H)‐3,1‐benzoxazine‐4‐ones is described using guanidinium chloride as a safe and convenient dehydrocyclization agent. High yields of the products obtain under mild reaction conditions without need to use of any catalyst and with easy work‐up of the reaction mixture.