Lithium bromide as an efficient,green, and inexpensive catalyst for the synthesis of quinoxaline derivatives at room temperature

Abstract

An efficient, simple, and green procedure for the synthesis of quinoxaline derivatives is described. The condensation of 1,2-diamines with 1,2-diketones using lithium bromide (LiBr) in H₂O/EtOH as a green reaction media at room temperature affords the title compounds in high to excellent yields and in short reaction times.     

Molecular iodine: a powerful catalyst for the easy and efficient synthesis of quinoxalines

Various biologically important quinoxaline derivatives were efficiently synthesized in excellent yields using inexpensive, nontoxic, and readily available bench top chemical, iodine in catalytic amount (10 mol %). Besides this, a systematic study was carried out to evaluate parameters such as solvent and catalyst loading. Several aromatic as well as aliphatic 1,2-diketones and aromatic 1,2-diamines, such as substituted phenylene diamines, tetra amines were further subjected to condensation using catalytic amounts of iodine to afford the products in excellent yield.     

Sonogashira cross-coupling of 3-bromo-1,2-diones: an access to 3-alkynyl-1,2-diones

A new general method for the synthesis of enols of cyclic 3-alkynyl-substituted 1,2-diketones is developed. Sonogashira cross-coupling of silyl enolates of cyclic 3-bromo-cyclopentane- and 3-bromo-cyclohexane-1,2-diones with variety of substituted acetylenes afforded enols of cyclic 3-alkynyl-1,2-diones with good yields (up to 93%) in a short reaction time. The starting 3-bromo-1,2-diones are easily obtainable by direct bromination of 1,2-diones with NBS.     

Fe3O4@SiO2/Schiff base complex of metal ions as an efficient and recyclable nanocatalyst for the green synthesis of quinoxaline derivatives

Fe₃O₄@SiO₂/Schiff base complex of metal ions catalyzed the reaction between phenylene-1,2-diamines and 1,2-diketones to produce quinoxalines in aqueous media at room temperature. This eco-friendly method provides several advantages such as mild reaction conditions, good to excellent yields, simple work-up, and nanocatalyst stability. Also, nanocatalyst can be simply recovered by a magnetic field and reused for at least five successive reactions.     

Ring-opening of tertiary cyclopropanols derived from β-diketones

The ring-opening reaction of 1,2-disubstituted cyclopropanols, prepared from β-diketones, mediated by Cu(NO₃)₂, p-TsOH, and NaOH is reported. The Cu(II)-mediated ring-opening of cyclopropanols gave α-methylene-γ-diketones in good yields. The reaction took place at the less substituted carbon of the cyclopropanols, involving mild conditions and a simple procedure. The reaction induced by p-TsOH in CH₂Cl₂ afforded α-methyl-γ-diketones as the major product with minor amounts of δ-diketones. The 2,3,5-trisubstituted furans were obtained in high yields when the ring-opening reaction was mediated by p-TsOH in methanol under reflux conditions. In the presence of sodium hydroxide the reaction proceeded smoothly in preference to the formation of δ-diketones, particularly for substrates with an aromatic group on the cyclopropane.     

Heterogeneous platinum catalytic aerobic oxidation of cyclopentane-1,2-diols to cyclopentane-1,2-diones

A method for the aerobic oxidation of cyclopentane-1,2-diols to the corresponding diketones over a commercial heterogeneous Pt/C catalyst is described. Unsubstituted and 3- or 4-substituted cyclopentane-1,2-diols are oxidized to 1,2-dicarbonyl compounds in good yields under the reported optimized reaction conditions (atmospheric air, 1 mol % of catalyst, 1 equiv of LiOH, aqueous solvents and 60 °C temperature). The method is applicable for producing cyclopentane-1,2-diketones in a scalable manner.     

Combining a Click–Multicomponent Reaction: One-Pot Synthesis of 1,2,3-Triazol-4-ylmethyl 3-Amino-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate Derivatives

(1,2,3-Triazol-4-yl)methyl-3-amino-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate derivatives were synthesized by a four-component, one-pot condensation reaction of benzaldehyde derivatives, an active methylene compound (prop-2-ynyl-2-cyanoacetate), azides, and phthalhydrazide in the presence of Cu(OAc)₂/sodium ascorbate as catalysts and 1-methyl-1H-imidazolium trifluoroacetate ([Hmim]TFA) as an ionic liquid medium in good to excellent yields.     

Facile Preparation of 1,2-Diketones

Easily accessible lead-like libraries of heterocyclic molecules useful for high-throughput screening are of continuous interest to the pharmaceutical industry. A number of drug-like libraries are derived from aromatic 1,2-diketones; however, nonsymmetrical 1,2-diketones are challenging to prepare. This communication describes a simple and practical synthesis of 1,2-diketones based on a controlled cross benzoin-like condensation reaction.     

One‐Pot Synthesis of Novel Pyrrolo[1,2‐a]quinoxaline‐4(5H)‐ones Using Benzene‐1,2‐diamine,Acetylenedicarboxylates, and β‐Nitrostyrene Derivatives

The reaction between a variety of o‐phenylenediamines (=benzene‐1,2‐diamines), dialkyl acetylenedicarboxylates, and derivatives of nitrostyrene (=(E)‐(2‐nitroethenyl)benzene) in the presence of sulfamic acid (SA; H₃NSO₃) as catalyst led to the corresponding pyrrolo[1,2‐a]quinoxaline‐4(5H)‐one derivatives in high yields.     

Revisiting the Hinsberg Reaction: Facile and Expeditious Synthesis of 3‐Substituted Quinoxalin‐2(1H)‐ones under Catalyst‐Free Conditions in Water

Substituted benzene‐1,2‐diamine reacted with various α‐keto esters at 50° under mild conditions for 15 min using H₂O as reaction medium, providing a variety of 3‐substituted quinoxalinone derivatives in excellent yields. The reaction was instantaneous, and products were isolated by simple filtration.     

Iron-promoted C-C bond cleavage of 1,3-diketones: a route to 1,2-diketones under mild reaction conditions

A conceptual method for the preparation of 1,2-diketones is reported. The selective C-C bond cleavage of 1,3-diketones affords the 1,2-diketones in high yields under mild reaction conditions in air by the use of FeCl(3) as the catalyst and tert-butyl nitrite (TBN) as the oxidant without the use of solvent. The possible reaction mechanism is discussed. This protocol provides an expeditious route to the useful 1,2-diketones.     

Asymmetric direct aldol reaction of 1,2-diketones and ketones mediated by proline derivatives

The direct aldol reaction of 1,2-diketones and ketones mediated by proline derivatives yields the corresponding 2-hydroxy 1,4-diketones in high regioselectivity, diastereoselectivity and good enantioselectivity. This reaction provides an easy access to optically active tertiary alcohols, which are flanked by two carbonyl groups for further elaborations.     

An effective synthesis of N,N-dimethylamides from carboxylic acids and a new route from N,N-dimethylamides to 1,2-diaryl-1,2-diketones

Carboxylic acids were heated at 150 °C in DMF in the presence of 1.25 equiv of thionyl chloride to give corresponding N,N-dimethylamides in good yields. Tandem chlorination and amidation reactions occurred in the one-pot procedure. Dicarboxylic acids needed prolonged reaction time to produce bisamides in good yields. Some benzamides were efficiently converted into corresponding 1,2-diaryl-1,2-diketones (benzils) under acyloin condensation conditions in the presence of 4,4′-di-tert-butylbiphenyl (DBB) in THF. Ultrasonic irradiation effectively accelerates the reaction, but it is not critical. However, the presence of DBB is fatal to the reaction. Although a few synthetic methods for benzils from benzoic acids have been reported so far, this method is one of the most convenient and highly reproducible procedures.     

Condensed Imidazo-1,2,4-azines. 31. Synthesis and Chemical Transformations of Substituted 1,2,4-Triazepino[2,3-a]benzimidazoles

By reaction of 1,2-diaminobenzimidazole with 1,3-diketones, acetoacetic ester and its derivatives, we have synthesized substituted 1,2,4-triazepino[2,3-a]benzimidazole and 5H-1,2,4-triazepino[2,3-a]benzimidazol-4-one. By reaction of 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazol-4-one with aromatic aldehydes or phenyldiazonium chloride, we have obtained 3-arylidene(phenylazo) derivatives of this compound, and by reaction with P₂S₅ we have obtained 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazole-4-thione. We have shown that when reacted with ammonia, primary or secondary amines, the latter forms 4-amino-substituted 2-methyl-1,2,4-triazepino[2,3-a]benzimidazole.     

Sulfamic Acid: A Mild,Efficient, and Cost-Effective Catalyst for Synthesis of Indoloquinoxalines at Ambient Temperature

A simple, cost-effective method for synthesis of indoloquinoxalines from isatin and o-phenylenediamine employing a catalytic amount of sulfamic acid at ambient temperature is reported. Moreover, the method is applicable for a variety of isatins, ninhydrin, 4-hydroxynaphthaquinone, and 1,2-diketones. The key features of the protocol include rapid reactions with good yields, simple workup procedure, and easy isolation of products.     

An efficient route to 4-aryl-5-pyrimidinylimidazoles via sequential functionalization of 2,4-dichloropyrimidine

[reaction: see text] Starting from 2,4-dichloropyrimidine, a concise synthetic route to medicinally important 4-aryl-5-pyrimidinylimidazoles is described. Sequential substitution of the 4- and 2-chloro groups using a regioselective Sonogashira coupling, followed by nucleophilic substitution, led to pyrimidinylalkyne derivatives, which were then oxidized to their corresponding 1,2-diketones. These 1,2-diketones, on cyclocondensation with ammonium acetate and an aldehyde, furnished the desired pyrimidinyl imidazoles in good overall yields.     

Samarium diiodide promoted formation of 1,2-diketones and 1-acylamido-2-substituted benzimidazoles from N-acylbenzotriazoles

N-Acylbenzotriazoles, when treated with samarium diiodide in THF, undergo self-coupling reaction to afford 1,2-diketones in good to excellent yields; while when treated with samarium diiodide in CH₃CN, they undergo ring-opening reaction to afford 1-acylamido-2-alkyl (or aryl) benzimidazoles in reasonable to good yields. A plausible mechanism was suggested.     

Synthesis of quinoxaline derivatives catalyzed by PEG-400

<正>Polyethylene glycol(PEG) was found to be an effective catalyst for the condensation of 1,2-diamines with 1,2-dicarbonyl compounds to afford the corresponding quinoxaline derivatives in excellent yields under mild reaction conditions.     

Polyethylene glycol-promoted synthesis of pyrimido[1,2-a]benzimidazole and pyrano[2,3-c]pyrazole derivatives in water

Synthesis of pyrimido[1,2-a]benzimidazole and pyrano[2,3-c]pyrazole derivatives were achieved using polyethylene glycol (PEG-400) as promoting reaction medium in water under catalyst-free conditions at reflux and room temperature, respectively. The structure of pyrimido[1,2-a]benzimidazole was confirmed using ¹H NMR, ¹³C NMR, DEPT, and HMBC experiments. The promising points for the present methodology are efficiency, generality, high yield, short reaction time, cleaner reaction profile, ease of product isolation, simplicity, potential of recycling reaction medium, and finally agreement with green chemistry protocols.     

In water organic synthesis: Introducing itaconic acid as a recyclable acidic promoter for efficient and scalable synthesis of quinoxaline derivatives at room temperature

Substituted quinoxaline derivatives are traditionally synthesized by co-condensation of various starting materials. Herein, we describe a novel environmentally benign in water synthetic route for the synthesis of structurally and electronically diverse ninety quinoxalines with readily available substituted o-phenylenediamine and 1,2-diketones using cheap and biodegradable itaconic acid as a mild acid promotor in 1 hours. The reaction is performed at room temperature, which proceeds through cyclo-condensation reaction followed by obtaining the aforesaid nitrogen-containing heterocyclic adducts without performing the column chromatography up to 96% total yields. The simplicity, high efficiency, and reusable of the catalyst merits this reaction condition as “green synthesis” which enables it to be useful in synthetic transformations upto gram scale level.