Oxidative Cyclocondensation Research Articles

An Atomic Cobalt Catalyst for the Oxidative Cyclocondensation of Benzoheterocycles

An Atomic Cobalt Catalyst for the Oxidative Cyclocondensation of Benzoheterocycles

Synthesis, and spectroscopic and structural characterization of three new styrylquinoline-benzimidazole hybrids.

Three new 4-styrylquinoline-benzimidazole hybrids have been synthesized using a reaction sequence in which 2-methylquinoline precursors first undergo selective oxidation by selenium dioxide to form the corresponding 2-formylquinoline intermediates, followed by oxidative cyclocondensation reactions with benzene-1,2-diamine to yield the hybrid products. The formyl intermediates and the hybrid products have all been fully characterized using a combination of IR, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry, and the structures of the three hybrid products have been determined using single-crystal X-ray diffraction. Ethyl (E)-2-(1H-benzo[d]imidazol-2-yl)-4-(4-chlorostyryl)quinoline-3-carboxylate, C27H20ClN3O2, (IIIa), and ethyl (E)-2-(1H-benzo[d]imidazol-2-yl)-4-(2-methoxystyryl)quinoline-3-carboxylate, C28H23N3O3, (IIIb), both crystallize in the solvent-free form with Z'= 1, but ethyl (E)-2-(1H-benzo[d]imidazol-2-yl)-4-(4-methylstyryl)quinoline-3-carboxylate, C28H23N3O2, (IIIc), crystallizes as a partial hexane solvate with Z'= 3, and the ester group in one of the independent molecules is disordered over two sets of atomic sites having occupancies of 0.765 (7) and 0.235 (7). The molecules of (IIIc) enclose continuous channels which are occupied by disordered solvent molecules having partial occupancy. In all of the molecules of (IIIa)-(IIIc), the styrylquinoline fragment is markedly nonplanar. Different combinations of N-H...O and C-H...π hydrogen bonds generate supramolecular assemblies which are two-dimensional in (IIIb) and (IIIc), but three-dimensional in (IIIa). Comparisons are made with the structures of some related compounds.

Transition-metal-free approach to quinolines via direct oxidative cyclocondensation reaction of N,N-dimethyl enaminones with o-aminobenzyl alcohols.

A transition-metal-free method for the construction of 3-substituted or 3,4-disubstituted quinolines from readily available N,N-dimethyl enaminones and o-aminobenzyl alcohols is reported. The direct oxidative cyclocondensation reaction tolerates broad functional groups, allowing the efficient synthesis of various quinolines in moderate to excellent yields. The reaction involves a C (sp3)-O bond cleavage and a C=N bind and a C=C bond formation during the oxidative cyclization process, and the mechanism was proposed.

Aspects of green chemistry toward synthesis of benzazoles and quinoxalines: Bovine serum albumin-water system for C–N/C–S bond formation

In this report, a biocatalytic divergent approach of therapeutically important five-membered benzazole heterocyclic compounds such as benzothiazoles and benzimidazoles has been described wherein Bovine serum albumin (BSA) and water play cooperative role for oxidative cyclo-condensation reaction between 2-mercapto/amino anilines and aromatic aldehydes under air at room temperature. Further, this green strategy also extended for the synthesis of privileged and biologically important six membered quinoxalines, 2-phenylimidazo [1,2-a]pyridine and benzo[d]imidazo[2,1-b]thiazoles. Moreover, the present biocatalytic protocol for the synthesis of such five- and six-membered heterocyclic compounds also have the added benefits of high atom economy, operational simplicity, excellent yields, recyclability (up to four cycles), and gram scalability.

NIS mediated dehydrogenative-cyclocondensation in aqueous medium towards the synthesis of 2-arylimidazo[1,2-a]pyridines and their 3-formylated derivatives

An environmental friendly, NIS mediated oxidative cyclocondensation of 2-aminopyridine and aryl methyl ketone/cinnamaldehydes has been realized for the synthesis of 2-arylimidazo [1,2-a]pyridines and their 3-formylated products respectively. This one pot protocol involves simple reaction conditions, tolerates wide range of substrates and the products were formed in good to excellent yields.

Environmentally Benign Synthesis of 4-Thiazolidinone Derivatives Using a Co/Al Hydrotalcite as Heterogeneous Catalyst

The present effort describes facile and environmentally benign synthesis of 4-thiazolidinone via oxidative cyclocondensation of benzyl alcohols, various substituted aromatic anilines and thioglycolic acid using a Co-Al hydrotalcite based heterogeneous catalyst (Co@HT) in methanol act as a solvent. We have synthesized three types of Co@HT with different molar ratio Co@HT-2 (1:1), Co@HT-3 (2:1), Co@HT-4 (3:1). Characterization of synthesized Co@HT catalyst using various analysis techniques such as FT-IR, powder XRD, SEM, XPS, EDS, DTG-TGA and N2 physical adsorption. Among the synthesized hydrotalcite, Co-HT-3 exhibit admirable catalytic activity towards oxidation of benzyl alcohol followed by cyclocondensation of respective aldehydes, anilines and thioglycolic acid into the corresponding 4-thiazolidinones in methanol at 60 οC using O2 as a oxidant. Furthermore, after end of the reaction, the catalyst is easily recovered and eco-friendly without any considerable loss in its catalytic efficiency.

Crystal structure of imidazo[1,5-a]pyridinium-based hybrid salt (C13H12N3)2[MnCl4

A new organic-inorganic hybrid salt [L]2[MnCl4] (I) where L + is the 2-methyl-3-(pyridin-2-yl)imidazo[1,5-a]pyridinium cation, is built of discrete organic cations and tetra-chlorido-manganate(II) anions. The L + cation was formed in situ in the oxidative cyclo-condensation of 2-pyridine-carbaldehyde and CH3NH2·HCl in methanol. The structure was refined as a two-component twin using PLATON (Spek, 2020 ▸) to de-twin the data. The twin law (-1 0 0 0-1 0 0.5 0 1) was applied in the refinement where the twin component fraction refined to 0.155 (1). The compound crystallizes in the space group P21/c with two crystallographically non-equivalent cations in the asymmetric unit, which possess similar structural conformations. The fused pyridinium and imidazolium rings of the cations are virtually coplanar [dihedral angles are 0.89 (18) and 0.78 (17)°]; the pendant pyridyl rings are twisted by 36.83 (14) and 36.14 (13)° with respect to the planes of the remaining atoms of the cations. The tetra-hedral MnCl4 2- anion is slightly distorted with the Mn-Cl distances falling in the range 2.3469 (10)-2.3941 (9) Å. The distortion value of 0.044 relative to the ideal tetra-hedron was obtained by continuous shape measurement (CShM) analysis. In the crystal, the cations and anions form separate stacks propagating along the a-axis direction. The organic cations display weak π-π stacking. The anions, which are stacked identically one above the other, demonstrate loose packing; the minimum Mn⋯Mn separation in the cation stack is approximately 7.49 Å. The investigation of the fluorescent properties of a powdered sample of (I) showed no emission. X-band EPR data for (I) at 293 and 77 K revealed broad fine structure signals, indicating moderate zero-field splitting.

Tandem Oxidative Cyclocondensation towards 2,3‐Disubstituted Quinazolinones in the Presence of [Bmim][BF4] and Iodine

The metal‐free synthesis of 2‐aryl‐3‐arylmethylquinazolin‐4(3H)‐one is achieved through ionic liquid mediated and I2‐promoted tandem oxidative cyclocondensation of isatoic anhydrides with arylmethylamines as the common precursor for the 2‐aryl and 3‐arylmethyl moieties. Radical quenching experiments suggest a non‐radical mechanistic pathway and the operation under anaerobic condition confirms the essential role of I2 as the oxidant. Metal‐free synthesis, reduced reaction times to afford higher product yields, recyclability of the IL used as the reaction medium, and the feasibility of gram scale operation are some advantages.

Application of laccase/DDQ as a new bioinspired catalyst system for the aerobic oxidation of tetrahydroquinazolines and Hantzsch 1,4-dihydropyridines

Laccase/DDQ as a new bioinspired quinone-based cooperative catalytic system was used for the biomimetic aerobic oxidative synthesis of 2-substituted quinazolines and Hantzsch pyridines from the oxidative cyclocondensation of 2-aminobenzylamine and aldehydes and the oxidative aromatization of 1,4-dihydropyridines, respectively. The products were obtained in good to high yields in a phosphate buffer (0.1 M, 12.5 mL, pH 4.5) and acetonitrile (4 vol%) mixture as a solvent. These methods are more eco-friendly, efficient, simple, and practical than other currently available ones because of mild reaction conditions and because they are free from any halide and toxic and expensive transition metals. Therefore, these methods can be applied in pharmaceutical and other sensitive synthetic procedures.

Ancistrocyclinones A and B, unprecedented pentacyclic N,C-coupled naphthylisoquinoline alkaloids, from the Chinese liana Ancistrocladus tectorius.

Two unique pentacyclic N,C-coupled naphthylisoquinolines, the ancistrocyclinones A (5) and B (6), were discovered in the Chinese liana Ancistrocladus tectorius. Furthermore, six known, likewise N,C-coupled alkaloids, viz., ancistrocladinium A (7a) and its mono- and bisphenolic analogs 8a and 9a were isolated, along with their atropo-diastereomers 7b, 8b, and 9b. The stereostructures of 5 and 6 were determined by HRESIMS, 1D and 2D NMR, oxidative degradation, and ECD calculations. The pentacyclic ancistrocyclinones A (5) and B (6) are structurally similar to berberine alkaloids - yet arising from a most different biosynthetic pathway: they are apparently formed by N,C-coupling of their polyketide-derived molecular halves, followed by oxidative cyclo-condensation. Biomimetic conversion of the co-occurring 4'-O-demethylancistrocladinium A (8a) to ancistrocyclinone A (5) via a quinoid intermediate supported the postulated pathway. Ancistrocyclinone A (5) was found to significantly inhibit the viability of drug-sensitive human leukemia (CCRF-CEM) and multidrug-resistant tumor cells (CEM/ADR5000) with comparable efficacies.

Synthesis of 2-substituted quinazolines by CsOH-mediated direct aerobic oxidative cyclocondensation of 2-aminoarylmethanols with nitriles in air

An atom-efficient synthesis of 2-substituted quinazolines is developed by a CsOH-mediated aerobic oxidative reaction of 2-aminoarylmethanols and nitriles in air.

Synthesis and Antimicrobial Screening of 2‐Aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of 2‐aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives was synthesized by condensation of 2‐(2‐substituted thiazol‐4‐yl)acetohydrazide with aryl aldehydes followed by oxidative cyclocondensation using iodobenzene diacetate. The structure of synthesized compounds was characterized by IR, NMR, and mass analysis. All the newly synthesized compounds were evaluated for their in vitro antimicrobial activity. Some of the compounds showed moderate antimicrobial activity.

Simple Synthesis of Benzazoles by Substrate-Promoted CuI-Catalyzed Aerobic Oxidative Cyclocondensation of o-Thio/Amino/Hydroxyanilines and Amines under Air

By catalyst and condition screening, a simple method for the synthesis of benzazole and quinoxaline heterocycles via Cu-catalyzed direct aerobic oxidative cyclocondensation of o-thio/hydroxy/aminoanilines and amines was developed by using air as the safe, cheap, effective, and clean oxidant. Due to the observed great promoting effect of the substrates on the reaction, single CuI can be used as the efficient catalyst without requiring additional oxidation co-catalysts. This method provides a simple and practical way for preparation of the useful benzothiazoles, benzimidazoles and benzoxazoles from amines.

Catalytic Oxidative Coupling of Primary Amines under Air: A Flexible Route to Benzimidazole Derivatives

AbstractBenzimidazoles are of fundamental importance in chemistry and biology, and the development of efficient, environmentally benign methods for their preparation remains a key challenge for organic chemists. In a biomimetic approach inspired by copper amine oxidases, we disclose herein the scope and factors influencing the success of the cooperative action of CuBr2 as electron‐transfer mediator and a topaquinone‐like substrate‐selective catalyst in the oxidative cyclocondensation of primary amines with o‐aminoanilines. This one‐pot atom‐economic multistep process, which works under green conditions with ambient air as the terminal oxidant, low loadings of catalyst, and equimolar amounts of commercially available amine substrates, is particularly suitable for the preparation of 1,2‐disubstituted benzimidazoles. Furthermore, it allows the functionalization of nonactivated primary aliphatic amines, which are known to be challenging substrates for non‐enzymatic catalytic aerobic systems.

ChemInform Abstract: Unexpectedly Simple Synthesis of Benzazoles by tBuONa‐Catalyzed Direct Aerobic Oxidative Cyclocondensation of o‐Thio/Hydroxy/Aminoanilines with Alcohols under Air.

tBuONa-catalyzed direct aerobic oxidative cyclocondensation reactions of readily available alcohols and o-thio/hydroxy/aminoanilines under air have been developed and provide an efficient, practical, and green method for the synthesis of benzazoles. Mechanistic studies revealed that o-substituted anilines promote the initial aerobic alcohol-oxidation step, which explains the high reactivity and success of this unexpectedly simple and practical cyclocondensation method.

An efficient practical chemo-enzymatic protocol for the synthesis of pyrazoles in aqueous medium at ambient temperature

An expeditious oxidative cyclocondensation reaction of hydrazines/hydrazides with 1,3-dicarbonyl compound was efficiently developed in aqueous medium using Saccharomyces cerevisae (baker's yeast) as a whole cell biocatalyst at room temperature. The method has been assigned using green chemistry measures and found to give a range of N-substituted pyrazoles with moderate to excellent yields (70–92%). The reaction progress was monitored by gas chromatography.

Unexpectedly Simple Synthesis of Benzazoles by tBuONa‐Catalyzed Direct Aerobic Oxidative Cyclocondensation of o‐Thio/Hydroxy/Aminoanilines with Alcohols under Air

tBuONa-catalyzed direct aerobic oxidative cyclocondensation reactions of readily available alcohols and o-thio/hydroxy/aminoanilines under air have been developed and provide an efficient, practical, and green method for the synthesis of benzazoles. Mechanistic studies revealed that o-substituted anilines promote the initial aerobic alcohol-oxidation step, which explains the high reactivity and success of this unexpectedly simple and practical cyclocondensation method.

Mechanistic studies of the tyrosinase-catalyzed oxidative cyclocondensation of 2-aminophenol to 2-aminophenoxazin-3-one

Tyrosinase (EC 1.14.18.1) catalyzes the monophenolase and diphenolase reaction associated with vertebrate pigmentation and fruit/vegetable browning. Tyrosinase is an oxygen-dependent, dicopper enzyme that has three states: Emet, Eoxy, and Edeoxy. The diphenolase activity can be carried out by both the met and the oxy states of the enzyme while neither mono- nor diphenolase activity results from the deoxy state. In this study, the oxidative cyclocondensation of 2-aminophenol (OAP) to the corresponding 2-aminophenoxazin-3-one (APX) by mushroom tyrosinase was investigated. Using a combination of various steady- and pre-steady state methodologies, we have investigated the kinetic and chemical mechanism of this reaction. The kcat for OAP is 75±2s−1, KMOAP=1.8±0.2mM, KMO2=25±4μM with substrates binding in a steady-state preferred fashion. Stopped flow and global analysis support a model where OAP preferentially binds to the oxy form over the met (k7≫k1). For the met form, His269 and His61 are the proposed bases, while the oxy form uses the copper-peroxide and His61 for the sequential deprotonation of anilinic and phenolic hydrogens. Solvent KIEs show proton transfer to be increasingly rate limiting for kcat/KMOAP as [O2]→0μM (1.38±0.06) decreasing to 0.83±0.03 as [O2]→∞ reflecting a partially rate limiting μ-OH bond cleavage (Emet) and formation (Eoxy) following protonation in the transition state. The coupling and cyclization reactions of o-quinone imine and OAP pass through a phenyliminocyclohexadione intermediate to APX, forming at a rate of 6.91±0.03μM−1s−1 and 2.59E−2±5.31E−4s−1. Differences in reactivity attributed to the anilinic moiety of OAP with o-diphenols are discussed.

Synthesis and antitubercular screening of some novel 4H-1,4- benzothiazines and their sulfones under environment benign solvent free conditions as future anti-tubercular agents.

Some novel analogs of 4H-1,4-benzothiazines were synthesized under environmentally benign solvent free conditions by one pot oxidative cyclocondensation of substituted 2- aminobenzenthiols with compounds having active methylene group and then converted in to sulfones. These compounds were examined as antitubercular agents against Mycobacterium tuberculosis H37Rv using REMA plate method. The best results have MICs from 6.4 to 8.8 μg/mL, comparable to phenothiazines. IR, NMR and mass spectral investigations are included for structural elucidation.

A short and efficient protocol for the synthesis of imidazo[1,5-a]quinoxalin-4-ones from 3-aroylquinoxalinones and compounds with the aminomethylene moiety

The reaction of 3-aroylquinoxalin-2(1H)-ones with α-amino acids and their derivatives, amines with various alkyl groups, amino alcohols with alkylene groups of various length, N-(3-aminopropyl)morpholine and 1,6-diaminohexane in DMSO at 150 °C proceeds through the oxidative cyclocondensation and makes it possible to synthesize substituted imidazo[1,5-a]quinoxalines. Depending on the compound with the aminomethylene fragment used the reaction allows to introduction of any given substituent into position 1.