Imidazolium-urea Low Transition Temperature Mixtures for the UHP-promoted oxidation of boron compounds

Different carboxy-functionalized imidazolium salts have been considered as components of low transition temperature mixtures (LTTMs) in combination with urea. Among them, a novel LTTM based on 1-(methoxycarbonyl)methyl-3-methylimidazolium chloride and urea has been prepared and characterized by differential scanning calorimetry throughout its entire composition range. This LTTM has been employed for the oxidation of boron reagents using urea-hydrogen peroxide adduct (UHP) as the oxidizer, thus avoiding the use of aqueous H2O2, which is dangerous to handle. This metal-free protocol affords the corresponding alcohols in good to quantitative yields in up to 5 mmol scale without the need of further purification. The broad composition range of the LTTM allows for the reaction to be carried out up to three consecutive times with a single imidazolium salt loading offering remarkable sustainability with an E-factor of 7.9, which can be reduced to 3.2 by the threefold reuse of the system.This work was financially supported by the University of Alicante (VIGROB-316, UAUSTI20-16), the Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-096616-B-I00), and the Generalitat Valenciana (AICO/2021/013). M.M. thanks the ISO (University of Alicante) for a predoctoral contract

Nickel-Imidazolium Low Transition Temperature Mixtures with Lewis-Acidic Character

Low transition temperature mixtures (LTTMs) are a new generation of solvents that have found extensive application in organic synthesis. The interactions between the components often generate highly activated, catalytically active species, thus opening the possibility of using LTTMs as catalysts, rather than solvents. In this work, we introduce a nickel-based imidazolium LTTM, study its thermal behavior and explore its catalytic activity in the solvent-free allylation of heterocycles with allylic alcohols. This system is effective in this reaction, affording the corresponding products in excellent yield without the need for additional purifications, thus resulting in a very environmentally friendly protocol.This research was funded by Ministerio de Ciencia e Innovación (grant number PID2021-127332NB-I00), Generalitat Valenciana (grant numbers AICO/2021/013 and IDIFEDER/2021/013) and University of Alicante (grant numbers VIGROB-316, UAUSTI22-23, UADIF22-104)

Iron-Based Imidazolium Salt as Dual Lewis Acid and Redox Catalyst for the Aerobic Synthesis of Quinazolines

A low transition temperature mixture formed with 1-butyl-3-(methoxycarbonylmethyl)imidazolium chloride and iron(III) chloride has proven to be an efficient catalyst for the synthesis of quinazolines following a sequence of condensation-cyclization-oxidation reactions. The protocol is simple and effective for coupling 2-acylanilines and benzylamines to form nitrogen containing heterocycles with moderate to excellent yields (up to 93%), being possible to perform the reaction in preparative scale. The functionalized imidazolium salt is crucial for the activation of the reagents under solvent-free conditions, and the presence of iron in the catalyst mediates the oxidation step with atmospheric oxygen. These features make the presented procedure better, from an environmental point of view, than other processes previously described. For this comparison, different "green" metrics have been used, such as atom economy, stoichiometric factor, reaction mass efficiency, E-factor and EcoScale.This work was financially supported by the University of Alicante (VIGROB-316, UADIF20-106, UAUSTI21-15), the Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-096616-B-I00), the Spanish Ministerio de Ciencia e Innovación (PID2021-127332NB-I00), and the Generalitat Valenciana (AICO/2021/013). M.M. thanks the ISO (University of Alicante) for a predoctoral contract

Metal–Organic Framework Based on Copper and Carboxylate-Imidazole as Robust and Effective Catalyst in the Oxidative Amidation of Carboxylic Acids and Formamides

A metal–organic framework (MOF) based on copper and 1,3-bis(carboxymethyl)imidazole (bcmim) was prepared on a gram scale by using a precipitation method at room temperature. The Cu(bcmim)2 MOF was shown to be an efficient catalyst for the preparation of amides through an oxidative coupling between carboxylic acids and formamides in the presence of an oxidant, such as tert-butyl hydroperoxide (TBHP). The method for the preparation of the amides is robust regardless of the carboxylic acid and gives good conversions with good selectivity. The heterogeneous catalyst was recovered unaltered after the reaction, was easily separated from the reaction mixture, and subsequently reactivated by suitable treatment. Moreover, the coupling reaction was scaled up to a gram scale, which allowed for the preparation of valuable products, such as fatty acid amides (i.e., 1-palmitoylpiperidine).The Spanish Ministerio de Economía y Competitividad (CTQ2015-66624-P) and the University of Alicante

DES-Type Interactions To Promote Solvent-Free and Metal-Free Reactions between Nitrogen-Containing Heterocycles and Allylic Alcohols

Nitrogen-containing heterocycles are of great interest to organic chemists since they are present in a wide array of bioactive molecules. The use of allylic alcohols to carry out the allylation of heterocycles has been described as a sustainable alternative for this type of functionalization. Among the plethora of methodologies described, the use of metals, solvents, or hazardous reagents is ubiquitous. The protocol described in this work has provided a solventless and metal-free alternative, being mediated by the easy-to-synthesise and reusable 1,3-bis(carboxymethyl)imidazolium chloride. The protocol has resulted compatible with several nitrogen-containing heterocycles (i.e. indole, pyrazole, triazole, tetrazole, carbazole, indazole, and benzotriazole) and allylic alcohols, providing the allylated-heterocycles with up to quantitative yield, being possible to perform the reaction in preparative scale.Based on various green metrics (atom economy, stoichiometric factor, reaction mass efficiency, materials recovery parameter, E-factor, and EcoScale), the overall greenness significance of the methodology has been established.This work was financially supported by the University of Alicante (VIGROB-316, UADIF20-106, UAUSTI21-15), the Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-096616-B-I00), the Spanish Ministerio de Ciencia e Innovación (PID2021-127332NB-I00) and the Generalitat Valenciana (AICO/2021/013). MM thanks the ISO (University of Alicante) for a predoctoral contract

1,3-Bis(3-carboxypropyl)-1H-imidazole

The use of γ-aminobutyric acid (GABA) as a starting material in a multicomponent reaction has resulted in the preparation of the zwitterionic 1,3-bis(3-carboxypropyl)imidazole (bcpim). The synthesis of this imidazole derivative in a one-pot procedure with stoichiometric amounts of the corresponding reagents (formaldehyde, glyoxal, and GABA in a 1:1:2 ratio) has resulted in a straightforward and effective methodology, meaning a significant improvement from a sustainable point of view.This research was funded by Ministerio de Ciencia, Innovación y Universidades (grant number PGC2018-096616-B-I00), Ministerio de Ciencia e Innovación (PID2021-127332NB-I00), Generalitat Valenciana (grant number AICO/2021/013), and the University of Alicante (grant number VIGROB-316)

Biscarboxy-Functionalized Imidazole and Palladium as Highly Active Catalytic System in Protic Solvents: Methanol and Water

The coupling reaction between aryl bromides and boron reagents is efficiently catalyzed by an in situ generated palladium complex obtained from palladium(II) acetate (0.1 mol%) and 1,3-bis(carboxymethyl)imidazole (0.2 mol%). The catalytic system is very active in protic solvents, especially in methanol. Biaryl derivatives have been prepared in good isolated yields (up to >99%), and additionally styrene and stilbene derivatives have also been prepared by means of this protocol.Financial support from the Ministerio de Ciencia e Innovación (MICINN) of Spain (Project Nos. CTQ2007-65218, CTQ2011-24165, Consolider Ingenio 2010 CSD2007-00006), the Generalitat Valenciana (PROMETEO/2009/039 and FEDER), and the Universidad de Alicante is acknowledged

1,2-Functionalized Imidazoles as Palladium Ligands: An Efficient and Robust Catalytic System for the Fluorine-Free Hiyama Reaction

A variety of hydroxy- and amino-functionalized imidazoles were prepared from 1-methyl- and 1-(diethoxymethyl)imidazole by means of isoprene-mediated lithiation followed by reaction with an electrophile. These compounds in combination with palladium acetate were screened as catalyst systems for the Hiyama reaction under fluorine-free conditions using microwave irradiation. The systematic study of the catalytic system showed 1-methyl-2-aminoalkylimidazole derivative L1 to be the best ligand, which was employed under solvent-free conditions with a 1:2 Pd/ligand ratio and TBAB (20 mol-%) as additive. The study has revealed an interaction between the Pd/ligand ratio and the amount of TBAB. The established catalytic system presented a certain degree of robustness, and it has been successfully employed in the coupling of a range of aryl bromides and chlorides with different aryl siloxanes. Furthermore, both reagents were employed in an equimolecular amount, without an excess of organosilane.Financial support from the Spanish Ministerio de Ciencia e Innovación (MICINN) (project numbers CTQ2007-65218, CTQ2011-24165), from Consolider Ingenio 2010 (CSD2007-00006), from the Generalitat Valenciana (PROMETEO/2009/039), from the Fondos Europeos para el Desarrollo Regional (FEDER) and from the Universidad de Alicante is acknowledged

1,3-Bis(carboxymethyl)imidazolium Chloride as a Metal-Free and Recyclable Catalyst for the Synthesis of N-Allylanilines by Allylic Substitution of Alcohols

The 1,3-bis(carboxymethyl)imidazolium chloride, which is easily and in a straightforward manner prepared readily from starting materials in multigram scale, is employed as catalyst in the synthesis of N-allylanilines by allylic substitution of alcohols with anilines. This metal-free catalyst allows the reaction to be carried out under mild reaction conditions (80 °C and air open vessel) and proved to be efficient for a diversity of anilines and allylic alcohols, providing exclusively the product of N-substitution independently of the substituents in the aniline reactant. The process described is simple and effective, allowing N-allylanilines to be obtained in preparative scale [e.g., 3.30 g of N-(1,3-diphenylallyl)-4-nitroaniline]. The catalyst could be reused up to 15 cycles without loss of activity, proving its robustness.This work was financially supported by the University of Alicante (VIGROB-285) and the Spanish Ministerio de Economía y Competitividad (CTQ2015-66624-P). M.A.S. thanks the Spanish Ministerio de Educación, Cultura y Deporte for a predoctoral fellowship (FPU15/06040)

Oxidative Coupling–Thionation of Amines Mediated by Iron-Based Imidazolium Salts for the Preparation of Thioamides

An efficient and selective multicomponent oxidative coupling, involving the use of two different amines, sodium phosphate, and elemental sulfur have been described for the preparation of thioamides, employing microwave irradiation. The use of an iron(III)-based imidazolium salt is essential as catalyst. Indeed, the iron-based catalyst is involved in the oxidative coupling of the two amines and in the subsequent C–S bond formation. The protocol is useful for a wide variety of primary benzylamines and alkylamines, as coupling partners. Thus, various electron-rich and electron-poor substituents in the aromatic rings and also fused piperidine derivatives, are suitable starting materials in this reaction. Some of the obtained products are important synthetic intermediates for natural products.This work was financially supported by the Spanish Ministry (Ministerio de Economía y Competitividad CTQ2015-66624-P) and the University of Alicante (VIGROB-285)