Convenient Synthesis of Structurally Novel 1,3‐Disubstituted Azetidine Derivatives

A convenient synthesis of structurally novel 1,3‐disubstituted azetidine derivatives is described. The approach involves condensation of an azetidine building block with sulfonylated carbamic acid methyl ester, subsequently followed by quenching the imidoyl chloride with amines. Different derivatives were prepared by substituting benzhydrol as well as benzenesulfonamide as part of the core structure.     

Synthesis of 4,4‐Disubstituted‐4H‐benzo[d][1,3]oxathiin‐2‐ones,a New Class of Compounds

4,4‐Dialkyl and 4,4‐diaryl‐4H‐benzo[d][1,3]oxathiin‐2‐ones were synthesized by the reaction of 2‐(mercapto‐phenyl)‐dialkyl‐ (or diaryl)‐methanol with CDI in excellent yield. The 2‐(mercaptophenyl)‐dialkyl‐ (or diaryl)‐methanols were prepared by the reaction of commercially available methylthiosalicylate with an appropriate alkyl or aryl Grignard reagent.     

Stereoselective Synthesis of 2,6‐Disubstituted Tetrahydropyridines Via Aza‐Diels‐Alder Reactions

Abstract

The aza‐Diels‐Alder reactions of (E)‐2‐(phenylthio)‐1,3‐pentadiene (2) with iminium salts gave the 2,6‐disubstituted tetrahydropyridines 3–8. Factors influencing the stereochemistry and reactivity of these reactions were also studied.     

Synthesis of 5‐Cyano‐1,3‐dioxoalkanes by Reaction of 1,3‐Dicarbonyl Dianions with Bromoacetonitrile

5‐Cyano‐1,3‐dioxoalkanes were prepared by reaction of 1,3‐dicarbonyl dianions with bromoacetonitrile.     

Sonochemical Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles in Aqueous Medium

An ultrasound‐accelerated fast and efficient three‐component reaction for the regioselective synthesis of l,4‐disubstituted 1,2,3‐triazoles using different alkyl and allyl halides, terminal alkynes, and sodium azide in water at room temperature has been developed using CuI as catalyst. Ultrasonication dramatically decreases the reaction times.     

Synthesis of 4‐Substituted‐ and 1,4‐Disubstituted‐4‐Hydroxypyrrolidin‐2‐ones

This report describes the synthesis of 4‐substituted‐ and 1,4‐disubstituted‐4‐hydroxypyrrolidin‐2‐ones by cyclization of intermediate γ‐aminoesters prepared from alkylbenzylamines, α‐bromoketones, and lithio ethyl acetate.     

Novel Copolymers of Vinyl Acetate and Halogen Ring‐Disubstituted 2‐Phenyl‐1,1‐dicyanoethylenes

Electrophilic trisubstituted ethylene monomers, halogen ring‐disubstituted 2‐phenyl‐1,1‐dicyanoethylenes, RC₆H₃CH?C(CN)₂ (where R is 2,3‐diCl, 2,4‐diCl, 2,6‐diCl, 3,4‐diCl, 3,5‐diCl, 2,4‐diF, 2,5‐diF, 2,6‐diF, 3,4‐diF, 3,5‐diF, 2‐Cl, 6‐F) were synthesized by piperidine catalyzed Knoevenagel condensation of ring‐substituted benzaldehydes and malononitrile, and characterized by CHN elemental analysis, IR, ¹H‐and ¹³C‐NMR. Novel copolymers of the ethylenes and vinyl acetate were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator (ABCN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C‐NMR, GPC, DSC, and TGA. High T_g of the copolymers, in comparison with that of polyvinyl acetate, indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. The gravimetric analysis indicated that the copolymers decompose in the 220–800°C range.     

Microwave‐Assisted Synthesis of N,N′‐Disubstituted Acetamidine Ligands

Under microwave activation, triethylorthoacetate reacts with the substituted anilines in the presence of acetic acid as a catalyst, producing acetamidine in moderate to high yields. The X‐ray structures of the new amidines, N,N′‐bis(3,5‐dimethylphenyl)‐acetamidine and N,N′‐bis(p‐tolyl)acetamidine, are also reported, revealing polymeric chains supported by intramolecular H‐bonds.     

Novel Copolymers of Vinyl Acetate with Alkyl and Alkoxy Ring‐Disubstituted 2‐Phenyl‐1,1‐dicyanoethylenes

Electrophilic trisubstituted ethylene monomers, alkyl and alkoxy ring‐disubstituted 2‐phenyl‐1,1‐dicyanoethylenes, RC₆H₃CH?C(CN)₂ (where R is 2,4‐(CH₃)₂, 2,5‐(CH₃)₂, 2,3‐(CH₃O)₂, 2,4‐(CH₃O)₂, 2,5‐(CH₃O)₂, 3,4‐(CH₃O)₂, 3‐C₂H₅O‐4‐CH₃O, 4‐CH₃O‐3‐CH₃), were synthesized by piperidine catalyzed Knoevenagel condensation of ring‐disubstituted benzaldehydes and malononitrile, and characterized by CHN elemental analysis, IR, ¹H‐ and ¹³C‐NMR. Novel copolymers of the ethylenes and vinyl acetate were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator (ABCN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C‐NMR, GPC, DSC, and TGA. High T _g of the copolymers, in comparison with that of polyvinyl acetate, indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. The gravimetric analysis indicated that the copolymers decompose in the 190–700°C range.     

Regiospecific Synthesis of Disubstituted Pyridin‐2‐ones and Trisubstituted Phenols with Vinamidinium Salts

A highly efficient and versatile method for the synthesis of 3‐acyl‐5‐aryl or arylsulfonylpyridin‐2‐ones and 3‐alkyl‐5‐aryl‐2‐hydroxybenzamides in one step via regiospecific cyclocondensation reaction of β‐keto‐amides with vinamidinium salts is described.     

Synthesis of Sterically Hindered 1,3‐Diketones

An efficient and practical method for the synthesis of sterically hindered aliphatic/aromatic 1,3‐diketones via coupling of ketones with esters using potassium tert‐butoxide is described. The protocol requires milder operating conditions, and the products are obained in good to excellent yields.     

Preparation of 2‐Amino‐1,3‐butadienes as N‐Pyridine Derivatives

2‐Amino‐1,3‐butadienes as pyridine derivatives have been prepared from corresponding dihydrothiazolo[3,2‐a]pyridinium salts in reactions with a strong base. The pyridinium salts were prepared from pyridine‐2(1H)‐thiones and trans‐1,4‐dibromo‐2‐butene by a vicinal and chemoselective formation of 3‐vinyldihydrothiazolo[3,2‐a]pyridinium salts. A strong base was used for selective proton removal from the vinyl‐substituted 3‐position. A subsequent ring opening provided 2‐substituted 1,3‐butadienes with the azine appended at the annular nitrogen. Simple S‐alkylation yielded a corresponding azinium salt, thereby introducing electrophilic character to the 1,3‐butadiene system. Hydrolysis of the sulfide function provided the corresponding pyridin-2(1H)‐one attached to the 1,3‐butadiene in the 2‐position.     

Novel Copolymers of Styrene and Halogen Ring‐Disubstituted 2‐Cyano‐N,N‐Dimethyl‐3‐Phenyl‐2‐Propenamides

Electrophilic trisubstituted ethylene monomers, halogen ring‐disubstituted 2‐cyano‐N,N‐dimethyl‐3‐phenyl‐2‐propenamides, RC₆H₃CH?C(CN)CON(CH₃)₂ (where R is 2,3‐dichloro, 2,4‐dichloro, 2,6‐dichloro, 3,4‐dichloro, 3,5‐dichloro, 2,3‐difluoro, 2,4‐difluoro, 2,6‐difluoro, 3,4‐difluoro, 3,5‐difluoro), were synthesized by potassium hydroxide catalyzed Knoevenagel condensation of ring‐substituted benzaldehydes and N,N‐dimethyl cyanoacetamide, and characterized by CHN elemental analysis, IR, ¹H‐ and ¹³C‐NMR. Novel copolymers of the ethylenes and styrene were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator, ABCN at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C NMR, GPC, DSC, and TGA. High T_g of the copolymers in comparison with that of polystyrene indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. The gravimetric analysis indicated that the copolymers decompose in the 300–450°C range.     

New Method for the Synthesis of 2‐Aza‐1,3‐Butadienes

2‐Aza‐1,3‐butadienes have been synthesized from carbonyl compounds and 1,1,1,3,3,3‐hexamethyl‐disilazane in the presence of cobalt‐containing catalysts. The best yields (up to 95%) were achieved in the case of aldehydes branched in the α-position and 2-methylcyclohexanone. In the case of two α,β‐unsaturated ketones, pyridine derivatives were found as the main products.     

Green Synthetic Method for 1,5‐Disubstituted Carbohydrazones

A green synthetic method for 1,5‐disubstituted carbohydrazones is described. The reaction of dimethyl carbonate with hydrazine hydrate first gave carbohydrazide, which further reacted with various aromatic aldehydes or aliphatic ketones under solvent‐free conditions to efficiently afford 1,5‐disubstituted carbohydrazone. This protocol has the advantages of using nontoxic dimethyl carbonate as starting material, no use of organic solvents, short reaction time, high yield, and simple workup procedure.     

Efficient One‐Pot Synthesis of 2‐Amino‐4,6‐diarylbenzene‐1,3‐dicarbonitrile under Solvent‐Free Conditions

A facile parallel synthesis of 2‐amino‐4,6‐diarylbenzene‐1,3‐dicarbonitrile derivatives via a one‐pot reaction of aromatic aldehydes, aromatic ketone, and malononitrile under solvent‐free conditions has been developed. This new protocol has the advantages of shorter time, higher yields, lower cost, and environmental friendliness.     

Copper‐ and Amine‐Free Sonogashira Reaction of N,N‐Disubstituted Propargylamine: Synthesis of Substituted Aryl Propargylamine

A copper‐ and amine‐free Sonogashira reaction of N,N‐disubstituted propargylamine (DEP) is reported. The procedure was mild and tolerated a series of aryl bromides, affording the substituted aryl propargylic amines in good to excellent yield.     

Synthesis of Substituted Tricyclo[5.3.1.04,9]undecan‐2,6‐dione from 4,4‐Disubstituted Cyclohexanone Enamines and Methacryloyl Chloride

Morpholine enamines 4‐acetyl‐4‐methyl‐1‐morpholinocyclohexene 4a, 4‐acetyl‐4‐phenyl‐1‐morpholinocyclohexene 4b, and 4‐acetyl‐4‐isopropenyl‐1‐morpholinocyclohexene 4c react with methacryloyl chloride to give 1,7‐dimethyl‐4(N‐morpholino) tricyclo[5.3.1.0^4,9]undecan‐2,6‐dione 9a , 1‐phenyl‐7‐methyl‐4(N‐morpholino) tricyclo[5.3.1.0^4,9]undecan‐2,6‐dione 9b , and 1‐ispropenyl‐7‐methyl‐4(N‐morpholino) tricyclo[5.3.1.0^4,9]undecan‐2,6‐dione 9c respectively, along with the corresponding substituted adamandane‐2,4‐diones.     

New Synthesis of 2‐Polyfluoroalkyl Substituted 1,4,5,6‐Tetrahydro‐pyrimidines and 4,5,6,7‐Tetrahydro‐1H‐1,3‐diazepines

A new efficient method for the preparation of 2‐polyfluoroalkyl substituted 1,4,5,6‐tetrahydropyrimidines and 4,5,6,7‐tetrahydro‐1H‐1,3‐diazepines by the reaction of polyfluoroalkanethiocarboxylic acids amides and 1,3‐propylenediamine or 1,4‐buthylenediamine is presented.     

Synthesis of Mesoionic 4‐(para‐substituted Phenyl‐5‐2,4‐dichlorophenyl)‐1,3‐4‐thiadiazolium‐2‐aminides by Direct Cyclization via Acylation of Thiosemicarbazides

The synthesis of ten novel mesoionic 4‐[para‐substituted (H, CH₃, OCH₃, NO₂, Cl, Br, OH, t‐C₄H₉, C₆H₅, C₄H₉) phenyl‐5‐2,4‐dichlorophenyl]‐1,3‐4‐thiadiazolium‐2‐aminides, as hydrochlorides, are described. The synthesis strategy utilized the corresponding para‐substituted isothiocyanates as starting materials to obtain the thiosemicarbazides through reaction with phenylhydrazine (61–98%), which were then submitted to acylation with 2,4‐dichloro benzoyl chloride and direct cyclization to generate the desired substituted mesoionic compounds in good yields (ca. 80%).