Alternate Method for the Synthesis of N‐Alkyl/aralkyl‐2‐(α‐hydroxy Alkyl/aralkyl)benzimidazoles via Regiospecific Acetylation

Acetylation of 1H‐2‐(α‐hydroxyalkyl/aryl)benzimidazoles 2 with Ac₂O results in the regiospecific formation of O‐acetoxy derivative 3, which on alkylation with alkylating agents in nonaqueous media under phase‐transfer catalytic conditions affords N‐alkyl derivatives 4. The latter, on hydrolysis in an aqueous basic medium, results in the title compounds 5 in good yields in high purity. Alternatively, 5 can also be obtained by reduction of 1‐substituted‐2‐acetyl/benzoylbenzimidazoles 8 using NaBH₄.     

Novel Regiospecific Method for Synthesis of 2‐(3,5‐Diaryl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐4,6‐diarylpyrimidines

The facile, regiospecific, one‐pot synthesis of 2‐(3,5‐diaryl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐4,6‐diarylpyrimidines derivatives has been described, involving a [3+2] and [3+3] cyclocondensation between the α,β‐unsaturated ketones and aminoguanidine bicarbonate.     

Synthesis,Structures and Properties of Polyimide Based on 2,2′‐Bis(4‐aminophenoxy phenyl) Propane

2,2‐Bis[4‐(4‐aminophenoxy)phenyl] propane (BAPP), as a monomer to prepare polyimide, was synthesized from Bisphenol A and p‐chloronitrobenzene via the nucleophilic substitution reaction. The structures of the diamine monomer BAPP and an intermediate dinitrocompound 2,2′‐bis(4‐nitrophenoxy phenyl) propane (BNPP) were confirmed by FTIR and NMR. A novel polyimide was derived from BAPP and 3,3′,4,4′‐oxydiphthalic dianhydride (ODPA) in DMAc by a two‐step method. FTIR, DSC, TGA, and DMA were employed to characterize the precursor and the polyimide. The glass transition temperature of the polyimide was about 225–230°C. The measurement of mechanical properties indicated that the polyimide exhibited a typical yield behavior of thermoplastic polymers, which is very different from other polyimides. The elongation at break of the polyamic acid and polyimide was 6% and 29%, respectively.     

Efficient Synthesis of (1R)‐[3,5‐Bis(trifluoromethyl)phenyl] Ethanol,a Key Intermediate for Aprepitant,an NK‐1 Receptor Antagonist

Enzyme‐catalyzed efficient synthesis of (1R)‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (R)‐(3), a key intermediate for aprepitant, via enantioselective transesterification of racemic 1‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (RS)‐3 using vinyl acetate as the acyl donor in the presence of Candida antarctica lipase‐B (CAL‐B) in an overall yield of 84% with >99% ee is described.     

Novel Synthesis and Characterization of 1,3‐Bis(2‐dihydrothiazolyl)thiaalkoxy‐p‐tert‐butylcalix[4]arenes

A novel series of 1,3‐bis(2‐dihydrothiazolyl)thiaalkoxy‐p‐tert‐butylcalix[4]arenes generated by the reaction between 4,5‐dihydrothiazole‐2‐thiol and the different dibromide calix[4]aryl groups have been synthesized and structurally characterized by IR, ¹H NMR, ¹³C NMR, and MS. From their analytical data, it was found that compounds 8, 9, and 10 had cone conformations, whereas compound 11 existed as a mixture conformation. To verify the structure of the synthetic compounds, a single‐crystal X‐ray structure of compound 8 was obtained.     

Efficient Microwave‐Assisted Synthesis of 9,9‐Bis[4‐(2‐hydroxyethoxy)phenyl]fluorene from 9‐Fluorenone and 2‐Phenoxyethanol

9‐Fluorenone (1) smoothly reacts with phenoxyethanol (2) in the presence of Al³⁺‐montmorillonite catalyst and 3‐mercaptopropionic acid as a cocatalyst under microwave irradiation at 160°C for 10 min to give 9,9‐bis[4‐(2‐hydroxyethoxy)phenyl]fluorene (3) in 81% yield, which was much higher than the yield of 33% obtained by conventional heating using an oil bath. A similar acceleration effect of microwave irradiation was observed in other metal‐cation‐exchanged montmorillonite catalysts as well.     

Improved Protocol for Thorpe Reaction: Synthesis of 4‐Amino‐1‐arylpyrazole using Solid–Liquid Phase‐Transfer Conditions

Solid–liquid phase‐transfer conditions were employed for the first time in the Thorpe reaction to synthesize 4‐amino‐1‐aryl‐3,5‐substituted‐1H‐pyrazoles 3. Aryl amines were diazotized and coupled with various active methylene compounds such as cyano acetamide, cyanoacetophenone, malononitrile, and ethyl cyanoacetate, resulting into α‐arylhydrazononitriles 1. Cyclization of 1 using α‐bromo ketones or esters resulted in compounds 3.     

Novel Synthesis of (3R,4R)‐4‐Acetoxy‐3‐[1′(R)‐tert‐butyldimethylsilyloxyethyl] Azetidin‐2‐one: A Key Intermediate for Penem and Carbapenem Synthesis

Diastereoselective synthesis of (3R,4R)‐4‐acetoxy‐3‐[1′(R)‐tert‐butyldimethylsilyloxyethyl] azetidin‐2‐one (AOSA) using (‐)‐D‐2,10‐camphorsultam as a key and recyclable chiral auxiliary is described.     

Synthesis of Some Novel 1,3,4‐Oxadiazol‐2‐yl‐4(3H)‐quinazolinones

N‐1‐Aroyl‐2‐{[(3‐methyl‐4(3H)‐quinazolinone‐2‐yl)methyl]anilino} ethano hydrazides (4), prepared from 2‐phenylaminomethyl‐3‐methyl‐4(3H)‐quinazolinone (1), underwent PPA‐catalyzed cyclization the to title compounds 5 in 51–67% yield.     

Novel Traceless Liquid‐Phase Synthesis of Coumarin Derivatives on Poly(Ethylene Glycol) Support

Coumarin derivatives were prepared by the von Pechmann reaction of PEG‐bound acetoacetate reagent with phenols in the presence of TiCl₄ in excellent yield and purity with a facile workup procedure. The polymer reagent could be recycled two to four times without diminishing the yield or purity.     

Novel Synthesis of 3‐Substituted 2‐Thiohydantoins via Aza‐Wittig Reaction on Poly(ethylene Glycol)

A novel method for the liquid‐phase combinatorial synthesis of 3‐substituted‐2‐thiohydantoin has been developed by using poly (ethylene glycol)–supported isothiocyanate. The PEG‐supported isothiocyanate was obtained from the reaction of PEG with bromoacetyl bromide, followed by an aza‐Wittig reaction. Reaction of PEG‐supported isothiocyanate with various aliphatic amines offered 3‐substituted 2‐thiohydantoins in excellent yields with addition, cyclization, and cleavage reactions occurred in one pot.     

Convenient and Efficient Synthesis of 1,1‐Bis‐(4‐alkylthiophenyl)‐1‐alkenes via Tandem Friedel–Crafts Acylation and Alkylation of Sulfides and Acyl Chlorides

1,1‐Bis(4‐alkylthiophenyl)‐1‐alkenes were conveniently and efficiently prepared from alkyl phenyl sulfides and acyl chlorides via a tandem Friedel–Crafts acylation and alkylation in the presence of anhydrous aluminum chloride. The scope, limitation, and mechanism of the tandem reaction were also discussed.     

Improved Synthesis of C 2‐Symmetric 4,4′‐α,ω‐Alkylenedioxy‐bis(3‐methoxybenzaldehydes)

Abstract

An improved Williamson synthesis of C ₂‐symmetric 4,4′‐(α,ω‐alkylenedioxy)‐bis(3‐methoxybenzaldehydes) from vanillin is described. These dialdehydes are often insoluble in cold acetone, which renders their purification especially facile.     

Solid‐Solid Phase and Solvent‐Free Oxidative Removal of N‐(4‐Alkoxyphenyl) Groups of Monocyclic β‐Lactams with Ceric Ammonium Nitrate as a Cheap,Simple, and Efficient Method

Five N‐(4‐methoxyphenyl)‐ and five N‐(4‐ethoxyphenyl)‐β‐lactams were prepared by ketene‐imine [2+2] cycloaddition (Staudinger reaction). Then these 2‐azetidinones were N‐dearylated by grinding together with ceric ammonium nitrate without hazardous solvents in good to excellent yields. The solid‐solid phase N‐dearylation is easier, simpler, and more efficient than the general method in solution. The pure N‐unsubstituted β‐lactams obtained by a nontedious workup and without further purification.     

A Simple Method for Synthesis of Methylene Dioximes Using Poly(ethylene glycol)‐400 as a Phase Transfer Catalyst

Abstract

A simple method for synthesis of methylene dioximes by reaction of ketoximes with dichloromethane in the presence of aqueous sodium hydroxide solution using poly (ethylene glycol)‐400 (PEG‐400) as a phase transfer catalyst is described.     

A Novel Method for the Synthesis of 2(3H)‐Benzimidazolones, 2(3H)‐Benzoxazolone,and 2(3H)‐Benzothiazolone via In Situ Generated Ortho Substituted Benzoic Acid Azides: Application of Ammonium Azide and Vilsmeier Complex for Acid Azide Generation

Abstract

An easy and generalized route to 2(3H)‐benzimidazolones, 2(3H)‐benzoxazolone and 2(3H)‐benzothiazolone is attempted. A novel one‐pot method for the in situ generation and cyclisation of ortho substituted benzoic acid azides is reported via the application of ammonium azide and Vilsmeier complex.     

Convenient One‐Pot Heterogeneous Catalytic Method for the Preparation of 3,4‐Dihydropyrimidin‐2(1H)‐ones

A new, simple, environmentally friendly synthesis of dihydropyrimidinones from aromatic and aliphatic aldehydes, ethyl acetoacetate, and urea or thiourea using a small‐pore‐size zeolite as catalyst is described. Compared with the classical Biginelli reaction conditions, this method has the advantage of high yield, shorter reaction time, and recyclable and reusable catalyst.     

Synthesis and Antioxidant Properties of Bis[ω-(3,5-dialkyl-4-hydroxyphenyl)alkyl] Sulfides

The reaction of -(3,5-dialkyl-4-hydroxyphenyl)-1-chloroalkanes with sodium sulfide yielded the corresponding sulfides, which were tested as antioxidants in two model reactions: oxidation of lard and Vaseline oil.     

Efficient Preparation of ((3‐Chloro‐2‐fluoro‐phenyl)‐[7‐methoxy‐8‐(3‐morpholin‐4‐yl‐propoxy)‐10,11‐dihydro‐5‐oxa‐2,4,11‐triaza‐dibenzo(a,d)cyclohepten‐1‐yl]‐amine) for In‐Vivo Study

An improved route for the preparation of highly functionalized 5,6‐dihydro‐pyrimido[4,5‐b][1,4]oxazepine 1a in multigram quantities was developed. This new methodology was highlighted by the proper methoxy disposition via a regioselective methylation of 2,4,5‐trihydroxy‐benzaldehyde followed by a magnesium sulfate–promoted cyclization.     

New Synthesis of 2,2‐Bis(hydroxymethyl) methylenecyclopropane,a Key Intermediate for Antiviral Cyclopropavir

Synthesis of 2,2‐bis(hydroxymethyl)methylenecyclopropane (2) is described. Cyclopropane dicarboxylate 3 was reduced to diol 4, which was acetylated to give diacetate 5. Acetoxy‐bromo elimination afforded methylenecyclopropane 6. Debenzylation gave the title compound 2.