Utility of 2-Methoxy-1-naphthaldehyde in Heterocyclic Synthesis

This review describes the synthesis and reactions of 2-methoxy-1-naphthaldehyde as building block and important intermediate for the synthesis of polyfunctionalized heterocyclic compounds with pharmacological interest.     

Synthetic Utility of Enaminonitrile Moiety in Heterocyclic Synthesis: Synthesis of Some New Thienopyrimidines

The hitherto unknown 3-amino-5-bromo-4, 6-dimethylthieno [2, 3-b] pyridine-2-carbonitrile ( 4 ) was condensed with p-anisaldehyde affording the Schiff base ( 5 ). Acylation of the thienopyridine derivative ( 4 ) using freshly distilled acetic anhydride gave a mixture of mono and diacetyl derivatives ( 6 ) and ( 7 ). Condensation of ( 4 ) with triethylorthoformate yielded the ethoxymethyleneamino derivative ( 8 ), which was treated with hydrazine hydrate to give the hydrazide derivative ( 9 ), which in turn was converted to a triazolopyrimidine derivative ( 10 ) upon treatment with freshly distilled acetic anhydride. Thiation of ( 4 ) with carbon disulfide afforded the pyrimidine dithione derivative ( 11 ), which was alkylated with ethyl iodide to give the di-s-ethylpyrimidine derivative ( 12 ).On the other hand, treatment of ( 4 ) with formamide yielded the aminopyrimidine derivative ( 13 ), whereas its treatment by formic acid produced the thienopyrimidinone derivative (1 4 ). Chlorination of (1 4 ) with a mixture of phosphorus pentachloride and phosphorus oxychloride gave the chloropyrimidine derivative ( 15 ), which in turn afforded the hydrazide derivative ( 9 ) upon treatment with hydrazine hydrate. Hydrazinolysis of ethyl-3-amino-5-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate ( 17 ) gave the hydrazino derivative ( 18 ), which in turn was converted to 8-bromo-7,9-dimethyl-3-formylaminopyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one ( 19 ) and 8-bromo-3-diacetylamino-2,7,9-trimethylpyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one ( 20 ) upon treatment with formic acid and freshly distilled acetic anhydride, respectively.     

Utility of 5-Amino-1-phenyl-1H-pyrazole-4-carboxamide in Heterocyclic Synthesis

This review presents a systematic and comprehensive survey of the methods of preparation and the chemical reactivity of 5-amino-1-phenyl-1H-pyrazole-4-carboxamide as building block for the synthesis of polyfunctionalized heterocyclic compounds with pharmacological interest.     

Phosphenium Cations in Heterocyclic Chemistry

Abstract

In the singlet state phosphenium cations feature both a vacant orbital and a lone pair at the phosphorus center (1). The anticipated amphoterism property of these species can be used for the synthesis of unusual heterocyclic derivatives. Our interest (2) in this type of chemistry bring us to report the reactions of stable phosphenium ions with unsaturated organic reactives i.e imines, a diimines, amidines and isocyanides.     

Synthesis,Chemistry and Applications of Heterocyclic Cage Compounds (V)

The synthesis and chemistry of polycyclic cage compounds have attracted considerable attention in recent years.¹ The vast majority of the work reported in this area has dealt with caybocyclic cage compounds. On the other hand, the synthesis and chemistry of heterocyclic cage compounds have received less attention. Recently, we have accomplished the synthesis of a series of oxa-cage compounds and performed the chemical transformations of these oxa-cage compounds.² As part of a program that involves the synthesis,chemistry and applications of heterocyclic cage compounds we report here the synthesis of heterocyclic cage compounds 1-12. We also wish to report the applications of compounds 7-12 on the π-facial selectivities. Studies on the cation-binding properties of compounds 1 and 2 and other oxa-cages are undertaken.     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Azepine,Azocine, and Pyrroldione Derivatives

Reactions of enaminonitrile derivative 3 with a variety of reagents lead to the syntheses of novel 1,2,4‐triazepin 7 , 1,4‐thiazepinone 9 , oxazocines 13 , 14 , oxadiazocines 15 , 16 , and pyrroldiones 17 , 18 , 19 , 20 , 21 22 with the aim to explore the use of this exceptionally reactive enaminonitrile 3 in heterocyclic synthesis. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and MS).     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Pyrazole,Pyridine, and Pyrimidine Derivatives

The starting (1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbonohydrazonoyl dicyanide ( 2 ) was used as key intermediate for the synthesis of 3‐amino‐2‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐ylazo)‐[3‐substituted]‐1‐yl‐acrylonitrile derivatives ( 3 – 10 ). In addition, nitrile derivative 2 reacted with hydrazine hydrate or malononitrile to afford the corresponding 3,5‐diaminopyrazole 11 and enaminonitrile derivative 13 , respectively. On the other hand, compound 3 was subjected to react with malononitrile, acetic anhydride, triethylorthoformate, N,N‐dimethylformamide (DMF)‐dimethylacetal, thiourea, and hydroxylamine hydrchloride to afford antipyrine derivatives 16 – 21 . Moreover, the reaction of enaminonitrile 3 with carbon disulfide in pyridine afforded the pyrimidine derivative 22 , whereas, in NaOH/DMF followed by the addition of dimethyl sulphate afforded methyl carbonodithioate 24 . The reaction of enaminonitrile derivatives 3 – 5 with phenylisothiocyanate afforded the thiopyrimidine derivatives 25a – c . Finally, the enaminonitrile 4 reacted with 3‐(4‐chloro‐phenyl)‐1‐phenyl‐propenone to afford the pyridine derivative 27 . The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹³C‐NMR, ¹H–NMR, and MS).     

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.     

Synthesis, Chemistry, and Applications of Heterocyclic Cage Compounds (V)

The synthesis and chemistry of polycyclic of cage compounds have attracted considerable attention in recent years. The vast majority of the work reported in this area has dealt with carbocylic cage compounds. On the other hand, the synthesis and chemistry of heterocyclic cage compounds have received less attention. Recently, we envisioned that studies on the synthesis and chemistry of heterocyclic cage compounds can greatly expand the scopes and utilities of cage compounds.1 As part of a program that involves the synthesis, chemistry, and application of heterocyclic cage compounds, we report here the synthesis of new thia-oxa-cage compounds and the chemical nature of these thia-cages.     

Expanding the Chemistry of Cationic N‐Heterocyclic Carbenes: Alternative Synthesis,Reactivity, and Coordination Chemistry

A new synthetic route to complexes of the cationic N‐heterocyclic carbene ligand 2 has been developed by the attachment of a cationic pentamethylcyclopentadienylruthenium ([RuCp*]⁺) fragment to a metal‐coordinated benzimidazol‐2‐ylidene ligand. The coordination chemistry and the steric and electronic properties of the cationic carbene were investigated in detail by experimental and theoretical methods. X‐ray structures of three carbene–metal complexes were determined. The cationic ligand 2 is a poorer overall electron donor relative to the related neutral carbene, which is evident from cyclic voltammetry (CV) and IR measurements.     

Phosphonitriles: Powerful Intermediates in Heterocyclic Chemistry

Abstract

Various phosphonitriles 2 have been generated by photolysis of the corresponding phosphine azides 1.     

Cyanothioacetamide in Heterocyclic Chemistry: Synthesis of Thiopyran,Pyridinethione, Thienopyridine,Pyridothienotriazine and Pyridothienopyrimidine Derivatives

Abstract

Cyanothioacetamide (1) reacted with α- and β-naphthaldehyde 2a,b to afford the corresponding 3-naphthyl-2-thiocarboxamidopropenonitriles 3a,b. Compounds 3a,b structures could be elucidated via their reactions with acrylonitrile, ethyl acrylate (4a,b). N-arylmaleimides 6a-c and ethyl acetoacetate (8). The isolated products could be represented as the thiopyran, thiopyranopyrrolidine and pyridinethione derivatives 5a-d, 7a-f and 9a,b respectively. Pyridinethiones 9a,b had been used as the starting materials in the present study in addition to the next ones to synthesize several new thienopyridines, pyridothienotriazine and pyridothienopyrimidines 12a-f, 15a,b, 16b, 17–19a,b respectively through their reactions with the corresponding reagents.

All structures of the newly synthesized heterocyclic compounds were established on the basis of the data of IR, ¹H NMR and elemental analyses.     

Cyanoacetamide Intermediate in Heterocyclic Synthesis: Synthesis and Biological Evaluation of Hitherto New Dioxoisoindoline Heterocyclic Derivatives

Innovative poly‐substituted heterocyclic rings incorporating dioxoisoindoline ( 2 – 25 ) were synthesized through the reaction of dioxoisoindoline derivative 2 as starting compound with various types of reagents. All compounds were characterized by appropriate means of (¹H‐NMR, ¹³C‐NMR, IR, and mass). The prepared compounds were evaluated as antimicrobial agents against Escherichia coli, Staphylococcus aureus, and Candida albicans microorganisms. The tested compounds exhibited low to moderate antibacterial activities and promising results as antifungal agents.