Highly Stereoselective Synthesis of New Aziridines via Baldwin Rearrangement and Their Potential Biological Activities

An atom‐economical conversion of N‐ substituted isoxazoline derivatives to new N‐ substituted aziridines has been described using microwave irradiation through Baldwin rearrangement. N‐ substituted isoxazoline derivatives have been synthesized using a variety of nitrones and alkynes via 1,3‐dipolar cycloaddition reactions in ionic liquid. Simple react\ion methodology, greener approaches, non involvent of catalysts, good to excellent yields, and cis diastereoselectivities are the important features noticed in this synthesis. Potential biological activity of the new aziridine derivatives made this protocol more attractive.     

Solvent-free synthesis and 1,3-dipolar cycloaddition reactions of N-methyl-C-(2-furyl) nitrone in a ball mill and anticancer activities of the new cycloadducts

An efficient method of mechanochemistry for the synthesis of N-methyl-C-(2-furyl) nitrone and intermolecular 1,3-dipolar cycloaddition reactions with activated alkenes and electron deficient alkynes has been studied by employing ball milling technique. This method is found to accelerate significantly the reaction rate and improved yields of isoxazolidine and isoxazoline derivatives. A comparative study with the corresponding solvent-free microwave-induced reaction showed the superiority of the ball milling method. Significant anticancer activity of the new molecules have made this protocol more attractive. All the new isoxazolidine and isoxazoline derivatives have been screened for anticancer activities and were found to be active.     

Synthesis and Characterization of Complexes of Copper(II), Nickel(II) and Cobalt(II) with vic-Dioximes Bearing N''-p-Aminobenzoyl Benzaldehyde Hydrazone

Six different arylhydrazone derivatives of p-aminobenzoic hydrazide of vic-dioximes were synthesized by reaction of chloroglyoxime and dichloroglyoxime with N＇-p-aminobenzoyl benzaldehyde, 4-hydroxybenzaldehyde and 4-methoxybenzaldehyde hydrazones, respectively. Metal-ligand （1 ： 2） complexes of vic-dioxime derivatives with Cu（Ⅱ）, Ni（Ⅱ） and Co（Ⅱ） were prepared from corresponding metal acetates. The ligands and their complexes were characterized on the basis of elemental analyses and spectral data. The complexing abilities of these new vic-dioximes toward transition metals of Co（Ⅱ）, Cu（Ⅱ）, Ni（Ⅱ）, Zn（Ⅱ）, Cd（Ⅱ）, Mn（Ⅱ） and Cr（Ⅲ） were determined by solid-liquid extraction studies.     

Synthesis and characterization of new 4,5-dihydropyrazol-1-yl derivatives

In this study, first, a series of chalcone compounds S1–S6 were synthesized from various acetophenone derivatives (acetophenone, p-methyl acetophenone, and p-methoxy acetophenone) and aromatic aldehyde derivatives (benzaldehyde, p-methyl benzaldehyde, and p-methoxy benzaldehyde) by the Claisen–Schmidt condensation reaction. These S1–S6 compounds were then used in the preparation of 4,5-dihydropyrazol-1-yl derivatives S7–S15. Finally, four new compounds S16–S19 were synthesized from compound (S7, S8, S9, and S12) and 2,4-dinitrophenylhydrazine. Therefore, three known and ten new heterocyclic compounds were synthesized and completely characterized using ¹H NMR, ¹³C NMR, IR, and elemental analysis.     

Reactions of heterocyclic paramagnetic aldonitrone, 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxide, with alkynes

The reactions of heterocyclic paramagnetic aldonitrone,viz., 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxide, with mono- and disubstituted alkynes afford unstable isoxazoline derivatives. The reactions with monosubstituted alkynes yield predominantly 5-substituted regioisomers. The resulting isoxazoline derivatives are readily (and often spontaneously) converted into enaminoketones,viz, imidazolidine-1-oxyl derivatives. In the presence of tolan, the title paramagnetic aldonitrone gives a dimer in which one imidazoline ring undergoes profound transformation. The structure of the resulting dimer was established by X-ray diffraction analysis. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 112–117, January, 2000.     

Reactions of heterocyclic paramagnetic aldonitrone, 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxide, with alkynes

The reactions of heterocyclic paramagnetic aldonitrone,viz., 2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxide, with mono- and disubstituted alkynes afford unstable isoxazoline derivatives. The reactions with monosubstituted alkynes yield predominantly 5-substituted regioisomers. The resulting isoxazoline derivatives are readily (and often spontaneously) converted into enaminoketones,viz, imidazolidine-1-oxyl derivatives. In the presence of tolan, the title paramagnetic aldonitrone gives a dimer in which one imidazoline ring undergoes profound transformation. The structure of the resulting dimer was established by X-ray diffraction analysis. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 112–117, January, 2000.     

Synthesis,Characterization, and Antioxidant Evaluation of Some Novel Pyrazolo[3,4‐c][1,2]diazepine and Pyrazolo[3,4‐c]pyrazole Derivatives

5‐Hydrazineyl‐3‐methyl‐1H‐pyrazole ( 1 ) was used as a starting material for the synthesis of novel pyrazolo[3,4‐c][1,2]diazepine derivatives 3 , 4 , and 6a,b by its reaction with acetylacetone, ethyl acetoacetate, and isatylidene derivatives 5a,b , respectively. Also, pyrazolo[3,4‐c][1,2]diazepine derivative 11 was synthesized via multicomponent reaction of 1 , benzaldehyde, and malononitrile. Moreover, compound 1 was used for synthesis novel pyrazolo[3,4‐c]pyrazole derivative 7 by its reaction with isatin. In addition, pyrazolo[3,4‐c]pyrazole derivatives 18a–c were synthesized by treatment of 2‐cyano‐N′‐(3‐methyl‐1H‐pyrazol‐5‐yl)acetohydrazide ( 13 ) with aromatic aldehydes 16a–c . The newly synthesized compounds were valeted by means of analytical and spectral data. All newly synthesized compounds were screened for their antioxidant activities. Compounds 3 , 13 , 18b , and 18c showed higher radical‐scavenging activities.     

Synthesis of 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives through cyclic transformations of 3‐(2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives

Four 3‐(3‐benzylidene‐2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives 3 have been synthesized from benzoxazolone derivatives 1 and benzaldehyde N‐chloroformylphenylhydrazone 2. By acid hydrolysis, these compounds yielded 3‐(2‐phenylcarbazoyl)‐2(3H)benzoxazolone derivatives 4 which were not isolated and were transformed via an intramolecular reaction into 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives 5 in a good yield. Attempts to cyclize these compounds by intramolecular elimination of water into tricyclic compounds 6 with various dehydrating agents were unsuccessful.     

Synthesis of Spirocyclic and Tricyclic Isoxazoline via 1,3‐Dipolar Cycloaddition Reactions

1,3‐Dipolar cycloadditions of the bicyclic monoterpenes (S)‐(?)‐camphene ( 1 ), (R)‐(+)‐a‐pinene ( 2 ), and (S)‐(?)‐b‐pinene ( 3 ) with aryl and heteroaryl nitrile oxides afforded new spirocyclic and tricyclic isoxazoline derivatives 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 whose biological activities were evaluated in bioassay studies.     

Synthesis of Ethyl Isoxazole‐3‐Carboxylates Using an Ionic Liquid as a Soluble Support

A regioselective 1,3‐dipolar cycloadditions of ionic liquid‐supported vinyl ethers, derived from ionic liquid‐supported α‐phenylselenomethyl ether, with ethyl cyanoformate N‐oxide gave supported isoxazoline derivatives, which were then cleaved from the ionic liquid support under mild acidic conditions to afford ethyl isoxazole‐3‐carboxylates. This new synthetic method is simple and efficient and the products are obtained in good yields.     

Conventional and Microwave‐Activated the Synthesis of a Novel Series of Imidazoles,Pyrimidines, and Thiazoles Candidates

A novel series of imidazoles, pyrimidines, and thiazoles were synthesized using microwave irradiation and conventional method from commercial available p‐aminobenzoic acid. Thus, one‐pot condensation of p‐aminobenzoic acid, urea, and chloroacetic acid have been provided two types of imidazole derivatives as separated mixture 2a and 2b . [3 + 2 + 1] Cyclocondensation of 2a , benzaldehyde, and urea/thiourea in acidic medium afforded imidazolo oxazine derivative 3 and Imidazolothiazine 4 . Coupling of 2a with benzene diazonium salt gave the phenyldiazenyl imidazolidine 5 . While the reaction of 2a , thiourea, and benzaldehyde in sodium ethoxide afforded imidazolothiazine 6 . Oxidative cyclization of thiourea derivative 7 resulted a mixture of benzithiazole derivative 7a and oxathiazole derivative 7b . Cyclocondensation of 7a with phenylenediamine and 4‐methyl phenylenediamine furnished imidazole 8 and 9 , respectively. Reaction of P‐aminobenzioc acid with potassium cyanate followed by Biginelli reaction with (acetyl acetone, ethyl acetoacetate, and diethyl malonate) and salicyladehyde in HCl tolerated pyrimidine derivatives 10a–c , respectively. In the same manner, the reactions and short reaction time make microwave technique one of the greenest methodology for synthesis of this class of heterocyclic system.     

Synthesis Through Three‐Component Reactions Catalyzed by FeCl3 of Fused Pyridocoumarins as Inhibitors of Lipid Peroxidation

2,4‐Diphenyl substituted fused pyridocoumarins have been synthesized by one‐pot three‐component domino reactions of aminocoumarins, benzaldehyde, and phenylacetylene by using FeCl₃ (10%) as catalyst under reflux or MW irradiation. The new compounds were tested as inhibitors of lipid peroxidation. The 7,9‐diphenyl‐2H‐pyrano[2,3‐g]quinolin‐2‐one presents interesting results and could serve as lead compound.     

Synthesis and Antimicrobial Evaluation of some Functionalized Heterocycles Derived from Novel Quinolinyl Chalcone

The reaction of 3‐acetyl‐4‐hydroxyl‐1‐methylquinolin‐2(1H )‐one (1) with 10‐oxo‐4,6,7,8,9,10‐hexahydropyrazolo[1,5‐a ][1]benzothieno[2,3‐d ]pyrimidine‐3‐carbaldehyde (2) afforded the novel enone system 3 . The latter compound was reacted with some 1,2‐binucleophilic reagents to give pyrazoline derivative 4 and isoxazoline derivative 5 . Treatment of chalcone 3 with 1,3‐binucleophilic reagents afforded pyrimidine and thiazine derivatives 6 – 8 . Moreover, reaction of compound 3 with active methylene reagents furnished pyridine, pyran, and cyclohexanone derivatives 9 – 12 . Cyclization of compound 12 by using hydrazine hydrate yielded indazol‐3‐one derivative 13. On the other hand, the cyclocondensation of the enone 3 with 1,4‐dinucleophilic reagents yielded diazepine derivative 14 and triazolothiadiazepine derivative 15 .The characterization of the newly synthesized heterocyles were confirmed on the basis of their elemental analysis and spectral data (IR, NMR, and MS). These compounds were also screened for their antibacterial activities.     

Novel Nano‐sized bis‐indoline Derivatives as Antitumor Agents

A facile access to novel bis‐(indoline‐2,3‐dione) was achieved via reactions of isatin with 1,3‐dibromopropane. The utility of the versatile bis‐(indoline‐2,3‐dione) in the design of new multifunctional building blocks using condensation with hydrazine derivatives was demonstrated. Moreover, a new series of bis‐thiazoles and bis‐thiazol‐4(5H)‐ones were synthesized by the reaction of bis‐thiosemicarbazone derivative with various derivatives of hydrazonoyl halides. The calculations derived from X‐ray diffraction patterns indicated the nanosize of the newly designed compounds. The spectral data of the formed compounds were established their structures. Also, the cytotoxic activity of the produced derivatives was screened against line MCF‐7 (breast cancer cell). It was found that four derivatives from nine investigated compounds showed activity more potent than the standard drug used by 20 times in some cases.     

tert-Amino effect in heterocyclic chemistry. Synthesis of hydrogenated spiro derivatives of quinolines

A new method was developed for the one-step synthesis of spiro derivatives of fused quinolines by the reactions of ortho-amino derivatives of benzaldehyde with Meldrum"s acid, cyclohexane-1,3-dione, or N,N"-disubstituted barbituric acids.     

Synthesis and Biological Activity of a Novel Pentacyclic Heterocycle

A novel pentacyclic heterocycle has been synthesized starting from D ‐glucose involving two crucial conversions: the intramolecular cycloaddition of O‐allyloxy furanaldoxime derived from D ‐glucose to furanopyran‐2‐isoxazoline and its diastereoselective reductive cleavage to the corresponding cis‐1,3‐amino alcohol. The antibacterial and antifungal activities of the synthesized heterocycle have been examined.     

Synthesis and Insecticidal Efficacy of Novel Bis Quinazolinone Derivatives

A novel bis benzoxazin‐4‐one derivative has been synthesized and utilized to construct a new series of bis quinazolin‐4(3H)‐one derivatives via the reactions with different nitrogen nucleophiles namely, primary amines (ammonia, ethanolamine, and 4‐aminoantipyrine), secondary amines (morpholine and piperidine), diamine (o‐phenylenediamine), hydrazine hydrate, and hydroxylamine. The insecticidal efficacy of newly synthesized compounds was also studied. The structural features of the synthesized compounds were assigned by spectral analysis.     

Chemistry of Dioxacyclanes: VII. Synthesis of 1,3-Dioxolane Derivatives from 3-(2-Propenyloxy)propane-1,2-diol and Their Properties

2,4-Disubstituted 1,3-dioxolanes were synthesized by reactions of benzaldehyde, its para-chloro derivatives, as well as 3-cyclohexenecarboxaldehyde with 3-(2-propenyloxy)-1,2-propanediol. Theproducts were brought into bromination, dichlorocarbene addition, and epoxidation reactions. It is found that when both components of the heterogeneous reaction of dioxolane ring formation have a double bond, the acid catalyst in strongly deactivated.     

Synthesis of Some Novel Heteroannulated Pyrano[3,2‐c]quinoline‐2,5(6H)‐diones

6‐Butyl‐3‐((dimethylamino)methylene)pyrano[3,2‐c]quinolinone and 6‐butyl pyrano[3,2‐c]quinolone‐3‐carbonitrile were efficiently synthesized in good yield. These two new precursors were used to obtain some novel heteroannulated pyrano[3,2‐c]quinolone derivatives from heterocyclization reactions with various binucleophiles. These heteroannulation reactions afforded novel heterocyclic systems fused to the pyranoquinolinone at face c, such as pyrazole, pyrimidine, pyridine, and pyrazolopyranone.     

Synthesis and Reactivity of 3‐oxoprop‐1‐en‐1‐olate Derivative as a Building Block for the Synthesis of Azole and Azine Derivatives

Several new heterocyclic compounds such as 7‐substituted pyrazolo[1,5‐a ]pyrimidine ( 5a–e ) derivatives have been synthesized by the reactions of the versatile unreported sodium 3‐(4‐methyl‐2‐(4‐methylphenylsulfonamido)thiazol‐5‐yl)‐3‐oxoprop‐1‐en‐1‐olate (2) with amino heterocyclic ( 3a–e ) derivatives. Reaction of (2) with hydrazonyl halide ( 7a–d ) and hydroximoyl chloride ( 11a,b ) derivatives followed by reaction with hydrazine hydrate afforded pyrazolo[3,4‐d ]pyridazine and isoxazolo[3,4‐d ]pyridazine derivatives, respectively incorporating a thiazole moiety have been described. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.