Production of pyrans, pyridazines, pyrimidines, pyrazines and triazine compounds using benzoylacetonitriles as a precursor

Benzoylacetonitriles are easily available and have high chemical reactivity due to the presence of three active moieties; nitrile, carbonyl, and active methylene functions. This review article represents a survey covering the synthetic strategies leading to five six-membered heterocycles; pyrans, pyridazines, pyrimidines, pyrazines, and triazine compounds; utilizing benzoylacetonitriles as starting precursor since 1985. The reactions are subdivided into groups that cover the synthetic methods of these heterocycles.     

Energetic analysis of the molecular packing of 5,5′‐dibromo‐2,2′‐bis[4‐(methylsulfanyl)phenyl]‐4,4′‐bipyridine: the role of π–π and halogen interactions

The crystal packing of the title compound, C₂₄H₁₈Br₂N₂S₂, is rationalized using the PIXEL method, which allows a separation of the intermolecular interaction energy into Coulombic, polarization, dispersion and repulsion contributions. Infinite (01) molecular planes are formed through π–π stacking and other minor interactions, including a Br...S contact, with the σ hole of the Br atom pointing towards the S‐atom lone pair. The title compound has crystallographically imposed twofold symmetry, with the twofold axis at the mid‐point of the central C—C bond.     

Sensitive voltammetric determination of paracetamol by poly (4-vinylpyridine)/multiwalled carbon nanotubes modified glassy carbon electrode

A novel glassy carbon electrode (GCE) modified with a composite film of poly (4-vinylpyridine) (P4VP) and multiwalled carbon nanotubes (P4VP/MWCNT GCE) was used for the voltammetric determination of paracetamol (PCT). This novel electrode displayed a combined effect of P4VP and MWCNT on the electro-oxidation of PCT in a solution of phosphate buffer at pH 7. Hence, conducting properties of P4VP along with the remarkable physical properties of MWCNTs might have combined effects in enhancing the kinetics of PCT oxidation. The P4VP/MWCNT GCE has also demonstrated excellent electrochemical activity toward PCT oxidation compared to that with bare GCE and MWCNT GCE. The anodic peak currents of PCT on the P4VP/MWCNT GCE were about 300 fold higher than that of the non-modified electrodes. By applying differential pulse voltammetry technique under optimized experimental conditions, a good linear ratio of oxidation peak currents and concentrations of PCT over the range of 0.02–450 μM with a limit of detection of 1.69 nM were achieved. This novel electrode was stable for more than 60 days and reproducible responses were obtained at 99% of the initial current of PCT without any influence of physiologically common interferences such as ascorbic acid and uric acid. The application of this electrode to determine PCT in tablets and urine samples was proposed.     

Acid-Promoted Oxygen-Atom Transfer from a Novel Dihydroisoquinoline-Derived Oxaziridine Substituted at Position 1

N-Alkyl-oxaziridines react in the presence of a nucleophile as an oxygenating agent; in the absence of a nucleophile, an isomerization reaction is observed. This study describes the synthesis of two new dihydroisoquinoline oxaziridines and their reactivity in an acid-promoted reaction in the presence and absence of sulfides.     

Simplified Approach to the Uncatalyzed Knoevenagel Condensation and Michael Addition Reactions in Water using Microwave Irradiation

Use of microwave irradiation in the synthesis of arylidenemalononitrile and benzopyran derivatives in water without catalyst is a clean method with high yield.     

α‐Cyanodithioic Acids and Their Corresponding Mono‐ and Dithiolate Salts as Building Blocks for the Synthesis of Novel Mercaptothiophenes

A novel and efficient method for the synthesis of mercaptothiophenes using cyanodithioic acids and their corresponding mono‐ and dithiolate salts as starting components is described.     

Ball Milling for Heterocyclic Compounds Synthesis in Green Chemistry: A Review

This review aims to present the application of ball milling for the synthesis ofdifferent heterocyclic compounds in very good yields. The method is a simple, economical, and ecofriendly process for synthesizing heterocycles, which is a large family of organic compounds. They are extremely important and have wide-ranging pharmaceutical and industrial applications.     

One-Pot New Synthetic Method for 3-Amino-2-quinoxalinecarbonitrile

A new method for the preparation of 3-amino-2-quinoxalinecarbonitrile ( 1 ) was studied. A successful condensation reaction between bromomalononitrile and o-phenylenediamine in the presence of Lewis acid catalyst (AlCl₃) was achieved to produce compound 1 .     

Synthesis and antitumor activity evaluation of some 1, 2, 4-triazine and fused triazine derivatives

Reactions of 3-hyrazino-5,6-diphenyl-1,2,4-triazine with various carbonyl compounds such as ethyl acetoacetate, acetylacetone, benzoin, isatin, phthalic anhydride, phenyl isocyanate and acetic anhydride were discussed. Its reactions with α, β unsaturated compounds such as arylidinemalononitrile, diethyl acetylenedicarboxylate, dibenzylidine hydrazine were studied. These reactions led to the formation of various triazine and fused-triazine derivatives. The antitumor activity of the synthesized compounds was tested against HePG2 and MCF-7 cell lines. Some of the tested compounds were most active, whereas other compounds exhibited little or no activity.     

Synthesis of Novel Bithiophene-Substituted Heterocycles Bearing Carbonitrile Groups

Symmetrical and unsymmetrical bithiophene-substituted heterocycles bearing carbonitriles including imidazo[1,2-a]pyridine, benzimidazole, and pyridine derivatives have been synthesized via different synthetic protocols. The bithiophene bis-imidazo[1,2-a]pyridine derivatives 3a,b were achieved in three steps starting from 2-acetyl-5-bromothiophene. Suzuki coupling reaction of 2a with 5-formylthiophen-2-ylboronic acid forms the formyl derivative 5, which by condensation with 3,4-diaminobenzonitrile in the presence of sodium bisulfite furnishes the unsymmetrical bithiophene derivative6. The bis-benzimidazole derivative 8 was obtained via hexabutylditin-mediated homocoupling of 5-bromothiophene-2-carboxaldehyde, while the benzimidazole derivatives 12a,b were prepared via the formyl derivatives 11a,b, a product of Velsmier formylation reaction of 10a,b. Two synthetic protocols for the aryl/hetaryl-2,2′-bithiophene derivative 14 have also been presented. In addition, the guanyl hydrazones of bithiophenes, 16 and 17, were prepared from bis(tri-n-butylstannyl)-2,2′-bithiophene through a Stille coupling reaction followed by a condensation step.