Synthetic and Mechanistic Studies on the Solvent-Dependent Copper-Catalyzed Formation of Indolizines and Chalcones

Copper nanoparticles supported on activated carbon have been found to catalyze the multicomponent synthesis of indolizines from pyridine-2-carbaldehyde derivatives, secondary amines, and terminal alkynes in dichloromethane; in the absence of solvent, however, heterocyclic chalcones are formed. We provide compelling evidence that both processes take place through aldehyde–amine–alkyne coupling intermediates. In contrast to other well-known mechanisms for chalcone formation from aldehydes and alkynes, a new reaction pathway involving propargyl amines as intermediates that do not undergo rearrangement is presented. The formation of indolizines or chalcones is driven by inductive and solvent effects, with a wide array of both being reported. In both reactions, the nanoparticulate catalyst has been shown to be superior to some commercially available copper catalysts, and it could be recycled in the case of the chalcone synthesis.This work was generously supported by the Spanish Ministerio de Economía y Competitividad (MINECO; CTQ2011-24151). M.J.A. and M.J.G.-S. acknowledge the Instituto de Síntesis Orgánica (ISO) of the Universidad de Alicante for both grants

SYNTHESIS CHARACTERISATION AND BIOLOGICAL EVALUATION OF (3Z, 4Z)-3, 4-BIS (SUBSTITUTED PHENYL BENZYLIDINE)-1-(4-SUBTITUTED PHENYL) PYROLIDINE-2, 5-DIONE

Objective: The present study focuses on synthesis and characterization of new series of bis-chalcone derivatives from cyclic imides and evaluating its antimicrobial activity against a pathogenic microorganism.Methods: The substituted cyclic imides 4-methyl phenyl pyrrolidine 2,5 dione 1 and 4-methoxy phenyl pyrrolidine 2,5 dione 2 were synthesized from succinic acid and primary aromatic amines. These cyclic imides condensed with substituted benzaldehydes in the presence of acetic acid furnished bis-heterocyclic chalcones and characterized by FT-IR, 1H NMR and also microbial activity was determined using the disc diffusion method.Results: The antimicrobial activity of bis-heterocyclic chalcones was tested against selective pathogens and the zone of inhibition was observed in E. coli, C. albicans and A. niger at 100µg/ml concentration.Conclusion: The compound (3Z,4Z)-3,4-bis-(2-hydroxybenzylidine)-1-p-tolylpyrrolidine-2,5-dione (3b) with methyl and hydroxyl substituent on benzene ring exhibited good antibacterial activity against E. coli and potent antifungal activity against C. albicans and A. niger.Keywords: Succinic acid, Cyclic imides, Pyrrolidine-2,5-dione, Bis-chalcon

Synthesis and antimicrobial test of heterocyclic chalcone containing oxygen

Chalcones (1,3-diaryl-2-propen-1-ones) which are belonging to flavanoid family is one of the classes of compounds which possess a wide range of biological activities such as antibacterial, anticancer, antifungal agents and others1. It was reported that heterocyclic chalcone bearing heterocycles such as furan ring has also significant property acting as antibacterial and antifungal agent2. Due to this potential, a series of heterocyclic chalcones were synthesized by focusing on varying the aromatic ketone containing halogen groups as these groups as reported to have significant activities towards selected bacterial strains. The reaction between 5-methylfurfural (1) with aromatic ketone (2a-e, 4 and 6) have successfully furnished products in high yields by conventional Claisen-Schmidt condensation method in the presence of base at room temperature (Scheme 1). The structures of the compounds were confirmed by spectroscopic method such as infrared spectroscopy (IR), nuclear magnetic resonance (1H and 13C NMR) and mass spectrometer (MS). All the synthesized compounds were screened for their antibacterial and antifungal activities

Synthesis and characterization of heterocyclic chalcones containing halogenated thiophenes

Heterocyclic chalcones containing halogenated thiophenes were synthesized. The first step was to synthesize 3-acetyl-2,5-dichlorothiophene and 2-acetyl-5-chlorothiophene as heterocyclic ketones by using Friedel-Crafts acylation. The ketones were then used to synthesize thiophene chalcones through Claisen-Schmidt reaction with the respective heterocyclic aldehydes such as 5-bromothiophene-2-carbaldehyde, 3-methyl-2-thiophene carboxaldehyde and 2-thiophene carboxaldehyde with 3-acetyl-2,5-dichlorothiophene or 2-acetyl-5-chlorothiophene in presence of basic medium, sodium hydroxide to form the corresponding chalcones. Structures of the synthetic compounds were confirmed by IR, MS, 1H and 13C NMR spectral data

Synthesis, antifungal and anti-hiv activities of new heterocyclic compounds

Thiophene chalcones, pyrazolines and 1,5-benzodiazepines are important heterocyclic compounds which show broad spectrum of biological activities. Three series of heterocyclic chalcones and their N-acetylated pyrazoline derivatives have been synthesized in low to good yields. The first step in this study is the synthesis of 3-acetyl-2,5-dichlorothiophene and 2-acetyl-5-chlorothiophene as heterocyclic ketones using Friedel-Crafts acylation. All thiophene chalcones were synthesized in three separate reactions by Claisen-Schmidt reaction of substituted thiophene aldehydes with ketones. Several acetophenone derivatives (series 2 and 3) were produced by cyclization reaction using hydrazine hydrate to form new and known N-acetylated pyrazoline derivatives. A series of substituted 1,5-benzodiazepines were synthesized in moderate to good yields. 4-Methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one was synthesized as starting material by reacting ortho phenylenediamine and crotonic acid in the presence of toluene. Cyclization of the starting material with appropriate acid chlorides, unsubstituted and five types of groups (fluoro, chloro, bromo, methyl and methoxy) attached at ortho, para and meta position of phenyl ring in the presence of triethylamine and anhydrous tetrahydrofuran have furnished substituted 1,5-benzodiazepines. The structures of the compounds were confirmed by infrared (IR), 1H NMR and 13C NMR (1D and 2D) nuclear magnetic resonance spectroscopies. Compounds of series 2 and 3 were tested for their antifungal activities against two types of pathogenic strains, namely Candida albicansa and Aspergillus niger with fluconazole as standard drug. The results for series 2 showed that the presence of bromo and methoxy substitution at para position on phenyl ring in chalcone and pyrazoline, respectively, resulted in significant enhancement in potency against both tested fungal strains with MIC value of ＞64 µg/mL. Compound carrying para fluoro on phenyl ring in pyrazoline derivatives exhibited the highest potency with MIC value of ＞32 µg/mL and 64 µg/mL against C. albicans and A.niger, respectively, among the series 3. The anti-HIV-1 RT assay of substituted 1,5-benzodiazepines (series 4) showed that the presence of chloro substitution at meta and ortho position inhibited the activity of HIV-1 RT with IC50 values 6.87 and 8.62 µM, respectively

Metal-free remote-site C–H alkenylation: regio- and diastereoselective synthesis of solvatochromic dyes

Lately, transition-metal catalysed C–H alkenylation of nitrogen heterocycles has gained increasing attention, often with the intervention of complex and expensive catalytic systems. On the other hand, both, chalcones and indolizines are versatile families of compounds with applications in diverse research areas, including materials science, because of their prominent photophysical attributes. We set forth herein the metal-free regio- and diastereoselective C–H alkenylation of indolizines through a very simple and mild acid–base approach. The most fascinating fact in this remote-site Csp2–Csp2 bond formation is that only one starting material is utilised, which undergoes a formal self-alkenylation to integrate a chalcone moiety and furnish a new family of dyes; a plausible reaction mechanism has been put forward. A one-pot multicomponent protocol was conceived that generates the starting indolizine in situ and has been extended to a multi-gram scale synthesis with equal efficiency. The dyes show a single structure in the solid state but two stable structures in solution (rotamers). Preliminary studies on the optical properties of the dyes reveal a particle-size dependent colour in the solid state and solvatochromism (i.e., different colours in solution depending on the solvent polarity). Remarkably, the solvatochromic behaviour was also displayed in plastics. We believe that this finding opens new avenues in the fields of heterocyclic chemistry, dyes, and materials science.This work was generously supported by the Spanish Ministerio de Economía y Competitividad (MINECO; CTQ2011-24151 and CTQ-2015-66624-P) and the Generalitat Valenciana (GV; grants no. APOTIP/2015/014 and AEST/2015/001). M. J. A. and M. J. G.-S. are grateful to the Instituto de Síntesis Orgánica (ISO) for both pre-doctoral grants (contracts no. I-PAS-44/13 and I-PAS-11/16)

Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate‐driven synthesis of β‐enaminones and N‐aryl pyrroles from indolizines and nitrosoarenes; aryl‐substituted indolizines lead to β‐enaminones in a regio‐ and diastereoselective manner, whereas alkyl‐substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the β‐enaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work.This work was generously supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MICIU; grant no. CTQ2017-88171-P), the Generalitat Valenciana (GV; grant no. AICO/2017/007), and the Instituto de Síntesis Orgánica (ISO). M.J.G.-S. is grateful to the ISO for a predoctoral grant (contract no. I-PAS-11/16)