Reduction Of Nitriles Research Articles

Catalytic Application of POSS–COF-[(Co(acetate)2] for Selective Reduction of Nitriles to Amines

We report the reticular synthesis and structural investigations through the spectroscopic analysis of a novel polyhedral oligomeric silsesquioxane (POSS)-modified framework, hereby ascribed as a catalyst for the selective reduction of aryl nitriles to amines. The integration of the unique features of the polyhedral oligomeric silsesquioxane with 2,2′-Bipyridine-4,4′-dicarboxaldehyde and subsequently coordination to cobalt acetate manifests a distinctive feature, which is a stable covalent bond between Co and the functionalized POSS, effectively preventing catalyst leaching. The cobalt acetate-modified POSS–COF, synthesized with this approach, underwent a comprehensive characterization employing various analytical techniques including FTIR, XRD, SEM, XPS, TGA, and 29Si NMR. This thorough characterization provides a detailed insight into the structural and chemical attributes of the catalyst. Our catalyst, with its exceptional catalytic efficiency in catalyzing reduction reactions compared to its homogeneous counterparts, and its distinctive three-dimensional metalated POSS system, shows outstanding catalytic performance attributed to its diverse coordination interactions with ligands. Moreover, this catalyst presents additional merits, such as facile recovery and recyclability, making it a promising candidate for sustainable and efficient catalytic processes and thus instilling hope for a greener future.

Spirocyclic Hybrids of Nortropane and 1,3-Oxazinan-2-one Fragments

AbstractWe report facile and versatile procedures for the synthesis of exo- and endo-isomeric spirocyclic hybrids of pharmacophoric (1R,5S)-8-azabicyclo[3.2.1]octane (nortropane) and 1,3-oxazinan-2-one fragments. Our approach consists of the hydrocyanation of endo- and exo-isomeric N-Cbz-protected nortropane-3-spiroepoxides, the reduction of hydroxy nitriles into amino alcohols, the synthesis of N-alkylated amino alcohols via reductive amination, the spirocyclization of the amino alcohols, N-alkylation of the unsubstituted 1,3-oxazinan-2-one fragment in the spiro compounds, and removal of the Cbz protecting groups.

Construction and characterization of Fe3O4@BAAH-CuCl nanomagnetic catalyst: catalysis research in synthesis of 2-aryl quinazolines from prepared benzylamines

We have constructed Fe3O4@BAAH-CuCl nanomagnetic catalyst in ChCl-Urea (choline chloride deep eutectic as solvent) as a highly efficient catalytic system for the preparation of 2-aryl quinazoline derivatives through one-pot, three-component reactions of 2-bromobenzaldehyde with primary amines and sodium azide under molecular oxygen. FT-IR, VSM, SEM, TEM, TGA, XRD, EDX, ICP-OES and elemental mapping analyses confirmed the fabrication of Fe3O4@BAAH-CuCl nanomaterial. In this project, we first prepared various derivatives of benzylamines from reduction of aryl nitriles, then used the benzylamine products as substrates in the three-component synthesis of 2-aryl quinazoline derivatives in the presence of Fe3O4@BAAH-CuCl/ChCl-Urea as an efficient catalytic system. Although the synthesized products (primary amines and 2-aryl quinazolines) were known, their physical state was confirmed with the reported samples in the literature and the structure of all the products confirmed by 1HNMR and 1CNMR.

Novel Synthetic Industrial Approach for Efficient Synthesis of Baclofen through C–C Bond Formation

AbstractBaclofen is an active pharmaceutical ingredient used for the treatment of muscle spasticity. We describe our efforts to develop a novel synthetic approach through C–C bond formation and a cost-effective route to baclofen. The synthesis involved a two-step approach through C–C bond formation using the extensively and commercially available starting material 4-chlorobenzyl cyanide with chloroacetic acid as a reagent in an aprotic solvent, followed by reduction of the nitrile functional group. The synthetic route to baclofen has been demonstrated to be commercially viable, cost-effective, and environmentally friendly. Execution of the developed process led to the isolation of (+)-baclofen in an overall yield of 60% at a multikilogram scale with >99.5% HPLC purity. This article also discusses the cost-effectiveness of the process, the impurity profiling, and the product quality.

Manganese catalysed reduction of nitriles with amine boranes.

The room temperature reduction of various nitriles using amine boranes (ABs) catalysed by a manganese(i) alkyl complex is described. Based on experimental findings, a plausible mechanistic scenario is presented. This includes the presence of two catalytic cycles, one for productive reduction of nitriles and one for hydrogen evolution.

Au nanoparticle-catalyzed double hydrosilylation of nitriles by diethylsilane.

We present the first example of Au-catalyzed reduction of nitriles into primary amines. In contrast to monohydrosilanes which are completely unreactive, diethylsilane (a dihydrosilane) is capable of reducing aryl or alkyl nitriles into primary amines under catalysis by Au nanoparticles supported on TiO2, via a smooth double hydrosilylation pathway. The produced labile N-disilylamines are readily deprotected by HCl in Et2O to form the hydrochloric salts of the corresponding amines in very good to excellent yields. The catalyst is recyclable and reusable at least in 5 consecutive runs.

Zinc-Catalyzed Chemoselective Reduction of Nitriles to N-Silylimines through Hydrosilylation: Insights into the Reaction Mechanism.

The N,N'-chelated conjugated bis-guanidinate (CBG) supported zinc hydride (Zn-1) pre-catalyzed highly challenging chemoselective mono-hydrosilylation of a wide range of nitriles to exclusive N-silylimines and/or N,N'-silyldiimines is reported. Furthermore, the effectiveness of pre-catalyst Zn-1 is compared with another pre-catalyst analogue, i.e., DiethylNacNac zinc hydride (Zn-2), to know the ligand effect. We observed that pre-catalyst Zn-1 shows high efficiency and better selectivity than pre-catalyst Zn-2 for reducing nitriles to N-silylimines. Mechanistic studies indicate the insertion of the C≡N bond of nitrile into Zn-H to form the zinc vinylidenamido complexes (Zn-1' and Zn-2'). The active catalysts Zn-1' and Zn-2' are confirmed by NMR, mass spectrometry, and single-crystal X-ray diffraction analyses. A most plausible catalytic cycle has been explored depending on stoichiometric experiments, active catalysts isolation, and in situ studies. Moreover, the synthetic utility of this protocol was demonstrated.

Titanium-Mediated Reduction of Carboxamides to Amines with Borane-Ammonia.

In this study, the successful titanium tetrachloride-catalyzed reduction of aldehydes, ketones, carboxylic acids, and nitriles with borane-ammonia was extended to the reduction (deoxygenation) of a variety of aromatic and aliphatic pri-, sec- and tert-carboxamides, by changing the stoichiometry of the catalyst and reductant. The corresponding amines were isolated in good to excellent yields, following a simple acid-base workup.

Recent Developments in Manganese, Iron and Cobalt Homogeneous Catalyzed Synthesis of Primary Amines via Reduction of Nitroarenes, Nitriles and Carboxamides

AbstractThe preparation of primary amines attracts huge attention in the molecular synthetic community. Indeed, amines play a crucial role in chemistry as they are important substructures in a huge amount of drug molecules, agrochemicals, dyes and molecular materials. Compared to stoichiometric reductions using metal hydride based reagents, the catalyzed reduction of nitroarenes, nitriles and carboxamides appears to be an attractive option, mainly when associated to first row transition metals such as manganese, iron, or cobalt. In this short review, we illustrate the progress achieved in homogeneous hydrogenation, hydrogen transfer, hydrogen borrowing and hydrosilylation of nitroarenes, nitriles and carboxamides.magnified image

A General Synthesis of Dihydronaphthyridinones with Aryl-Substituted Quaternary Benzylic Centers

A variety of 7,8-dihydro-1,6-naphthyridin-5(6H)-ones and 3,4-dihydro-2,7-naphthyridin-1(2H)-ones with quaternary centers and aryl substitutions at the benzylic carbon were synthesized with a new 3-step, 2-pot method. The first step is an SNAr using widely available 2- and 4-chloronicotinate esters and tertiary benzylic nitriles. The last two steps are a one-pot selective nitrile reduction in the presence of various heterocycles followed by a lactam ring closure of the free amine on the ester.

A robust Zintl cluster for the catalytic reduction of pyridines, imines and nitriles.

Despite p-block clusters being known for over a century, their application as catalysts to mediate organic transformations is underexplored. Here, the boron functionalized [P7] cluster [(BBN)P7]2- ([1]2-; BBN = 9-borabicyclo[3.3.1]nonane) is applied in the dearomatized reduction of pyridines, as well as the hydroboration of imines and nitriles. These transformations afford amine products, which are important precursors to pharmaceuticals, agrochemicals, and polymers. Catalyst [1]2- has high stability in these reductions: recycling nine times in quinoline hydroboration led to virtually no loss in catalyst performance. The catalyst can also be recycled between two different organic transformations, again with no loss in catalyst competency. The mechanism for pyridine reduction was probed experimentally using variable time normalization analysis, and computationally using density functional theory. This work demonstrates that Zintl clusters can mediate the reduction of nitrogen containing substrates in a transition metal-free manner.

Ligand-metal cooperativity in quinonoid based nickel(II) and cobalt(II) complexes for catalytic hydrosilylative reduction of nitriles to amines: electron transfer and mechanistic insight.

The sustainable production of privileged amines by the catalytic reduction of nitriles with an inexpensive silane polymethylhydrosiloxane (PMHS) holds great promise to replace conventional synthetic routes that have limited applicability and involve the use of expensive metal catalysts. The use of late 3d-metal complexes provides an excellent platform for the rational design of inexpensive catalysts with exquisite control over their electronic and structural features through metal-ligand cooperativity. In this context, we have realistically designed two complexes based on nickel(II) and cobalt(II) with a redox-active imino-o-benzoquinonato ligand. The compounds were characterized by a suite of spectroscopic methods, cyclic voltammetry and single-crystal X-ray diffraction. Both complexes showed excellent catalytic activity in transforming various organonitriles into the corresponding primary amines selectively using the inexpensive PMHS. The catalytic performance of the complexes was evaluated by various control experiments and spectroscopic studies with detailed computational calculations revealing the crucial role of the non-innocent imino-o-benzoquinonato ligand and metal(II) ion cooperativity in controlling the reactivity and selectivity of the key metal-hydride intermediates in the course of catalytic reduction.

Electrochemical and in-situ spectroelectrochemical properties of novel (5-(tert-butyl)-2-((3,4-dicyanophenoxy)methyl)phenyl)methanolate substituted mononuclear metal phthalocyanines

This work involves the synthesis and characterization of metallic (Co, Fe, Mn, Ni, Zn) ball-type phthalocyanine precursors by using novel 4,4′-(((4-(tert-butyl)-1,2-phenylene)bis-(methylene))bis(oxy))diphthalonitrile starting compound. The classical oxo-bridge in phthalocyanines was altered with the -OCH2- bridge first time for these ball-type phthalocyanine precursors, and the effects of this change on the chemical, physical and spectral features of phthalocyanine complexes were investigated, in the study. The redox properties of phthalocyanines were researched by electrochemical and in situ spectroelectrochemical measurements on a Pt working electrode in non-aqueous medium. The color changes involved in the redox processes were observed via in situ electrocolorimetric techniques. Electrochemical and UV–Vis spectral measurements exhibited that the compounds had reversible and serial one-electron reduction and oxidation processes. Furthermore, they also had nitrile reduction processes because of opened nitrile groups located at peripheral tails of the phthalocyanine complexes. The plentiful redox conducts of the complexes such as Pc ring based and/or central redox active metal-based reduction and oxidation reactions at low potentials showed that these complexes can be used as functional materials. Because of the apparent spectral and net color changes, the complexes are suitable for utilization in electrochromic devices. Moreover, their rich redox features are a sign of their high electrocatalytic activity for oxygen reduction.

Noncatalyzed Reduction of Nitriles to Primary Amines with Ammonia Borane.

The preparation of primary amines from nitriles has been a subject of continuing interest, and many different methods have been reported for this process. We report in this paper an alternative method for transforming nitriles into primary amines. In this work, a wide range of nitriles were reduced to primary amines by 1.2 equiv of ammonia borane under thermal decomposition conditions without any catalyst and the corresponding primary amines were isolated in good to excellent yields. The reactions are environmentally benign with H2 and NH3 generated as byproducts. The reactions are also tolerant of many functional groups. Nitriles are likely reduced by the in situ-generated aminodiborane, the application of which in organic synthesis has never been reported before. By using our protocol, primary amines containing multifluorinated aromatic rings, which are greatly important in pharmaceutical synthesis and have rarely been prepared via catalytic processes, were successfully prepared.

B-N/B-H Transborylation: borane-catalysed nitrile hydroboration.

The reduction of nitriles to primary amines is a useful transformation in organic synthesis, however, it often relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal of a double B–N/B–H transborylation mechanism.

Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging.

Deciphering the drug/virus/host interactions at infected cell reservoirs is a key leading to HIV-1 remission for which positron emission tomography (PET) imaging using radiolabeled antiretroviral (ARV) drugs is a powerful asset. Dolutegravir (DTG) is one of the preferred therapeutic options to treat HIV and can be isotopically labeled with fluorine-18. [18F]DTG was synthesized via a three-step approach of radiofluorination/nitrile reduction/peptide coupling with optimization for each step. Radiofluorination was performed on 2-fluoro-4-nitrobenzonitrile in 90% conversion followed by nitrile reduction using sodium borohydride and aqueous nickel(II) chloride with 72% conversion. Final peptide coupling reaction followed by HPLC purification and formulation afforded ready-to-inject [18F]DTG in 5.1 ± 0.8% (n = 10) decay-corrected radiochemical yield within 95 min. The whole process was automatized using a TRACERlab® FX NPro module, and quality control performed by analytical HPLC showed that [18F]DTG was suitable for in vivo injection with >99% chemical and radiochemical purity and a molar activity of 83 ± 18 GBq/µmol (n = 10). Whole-body distribution of [18F]DTG was performed by PET imaging on a healthy macaque and highlighted the elimination routes of the tracer. This study demonstrated the feasibility of in vivo [18F]DTG PET imaging and paved the way to explore drug/virus/tissues interactions in animals and humans.

Bicyclic (alkyl)(amino)carbene (BICAAC) as a metal-free catalyst for reduction of nitriles to amines.

Bicyclic (alkyl)(amino)carbene (BICAAC) is introduced as a metal-free catalyst for the reduction of various nitriles to the corresponding amine hydrochloride salts in the presence of pinacolborane. Mechanistic investigations combining experiments and DFT calculations suggest a B-H addition to the carbene center, which acts as a carrier of the hydride source.

STUDY OF THE INFLUENCE OF DISPERSITY AND CHEMICAL COMPOSITION OF NICKEL RENEUAL ALLOYS ON THE SPECIFICITY OF REDUCTION OF ADAMANTANE-CONTAINING UNSATURED NITRILE

The regularities of the reduction of adamantane-containing unsaturated nitrile-nickel-aluminum alloy are investigated. It has been shown that under the conditions of synthesis it is possible to carry out the simultaneous reduction of both the double bond and the nitrile group. It was found that the reduction of nitriles containing 1 hydroxyl group in the position leads to a significant decrease in the rate of the process. The effect of the grain size composition of the alloy and damping additives on the reduction of unsaturated nitriles has been studied.

Copper-Catalyzed One-Pot Synthesis of Quinazolinones from 2-Nitrobenzaldehydes with Aldehydes: Application toward the Synthesis of Natural Products.

A novel, efficient, and atom-economical approach for the construction of quinazolinones from 2-nitrobenzaldehydes has been unveiled via copper-catalyzed nitrile formation, hydrolysis, and reduction in one pot for the first time. In this reaction, urea is used as a source of nitrogen for nitrile formation, hydrazine hydrate is used for both the reduction of the nitro group and the hydrolysis of nitrile, and atmospheric oxygen is used as the sole oxidant. The method portrays a wide substrate scope with good functional group tolerances. Moreover, this method was applied for the synthesis of schizocommunin, tryptanthrin, phaitanthrin-A, phaitanthrin-B, and 8H-quinazolino[4,3-b]quinazolin-8-one.

Organosilanes in Metal-Catalyzed, Enantioselective Reductions

The growth and development of an extensive range of metals complexed with chiral ligands for the purpose of catalyzing a variety of reactions in an enantioselective manner has been impressive for its scope, chemical yields and high ee values. Chief among the classes of synthetic transformations has been that of the asymmetric reduction of prochiral substrates. These include the asymmetric reduction of prochiral ketones, imines, unsaturated aldehydes, ketones, esters, nitriles and olefins, as well as a number of asymmetric coupling reactions. In concert with these efficient catalyst systems, organosilanes have the ability to carry out any number of organic reductions under a variety of conditions. In these reactions, which in reality are hydrosilylations (hydrosilylation and reduction are considered interchangeable herein) in which the initially resulting silylated product is hydrolyzed to the ultimate desired functionality, the ability to sterically and electronically alter the organosilane reductant can contribute to the overall success of the transformation. In this review, we present a thorough compilation of the literature covering the use of organosilanes in metal-catalyzed asymmetric reductions (hydrosilylations) and coupling reactions.