Cyanide Reagents Research Articles

Pozyskiwanie złota ze słowackiego koncentratu przy użyciu innowacyjnej metody

The complicated processing of concentrates with low gold content and the long-time use of non-ecological methods was the motion for finding a more efficient process for this noble metal obtaining. From this point of view, this research was focused on obtaining of nano gold from the concentrate White Hill (Detva, Slovakia) using mechanical activation and mechano-biological activation in a molecular hydrogen solution. Gold in this complex concentrate occurs physically enclosed in the intercrystalline space of minerals and is also isomorphic and fills defects in their structure. The exclusion of gold from such complex mineral matrixes of the concentrate can be achieved using a mechano-biological process. This innovative method for obtaining of nano gold with the application of a molecular hydrogen solution is an advantageous alternative to the non-environmental reagents used. Compared to the most used worldwide toxic cyanide reagent, a solution with molecular hydrogen represents a low-cost and above all completely harmless reagent with very good kinetics. Mechanical processes use high-energy milling, which has an effect on the more intensive formation of surface and bulk defects in solid substances. The main advantage of mechanical processes is a smaller number of technological operations, a shorter time required to obtain the desired product at favorable environmental temperatures, and also the formation of nanostructures. The use of a biological process with the application of limnetic algae showed that algae with siliceous structures make it possible to obtain gold from the White Hill concentrate with nanoscale size. Limnetic algae (diatoms, golden algae) are part of aquatic ecosystems and create the largest matter of biomass from all plants on the Earth. The mechano-biological process is a method that enabled to obtain of gold nanoparticles with an average size of 100 nm from the Slovak gold-bearing concentrate from the White Hill deposit (BV-1). Mechanical activation of this concentrate and siliceous shells of the specified limnetic algae (Dinobryon, Surirella) in a molecular hydrogen solution caused changes in the physical-chemical properties of gold minerals as well as in the constituents of algae minerals. These structural changes had a decisive influence on the exclusion of gold nanoparticles into the molecular hydrogen solution under the defined reaction conditions. The gold nanoparticles were subsequently fixed in the cellular matrix of mechanically activated algae shells. The explanation of this phenomenon was the action of biomolecules, which the algae cells secreted in the course of reactions with metal ions present in the molecular hydrogen solution. Gold nanoparticles from the investigated concentrate were obtained by a new mechano-biological procedure already for four hours. In the case of mechanical activation of the concentrate, but without activation of the used algae, gold nanoparticles were excluded after sixteen hours. It follows from this knowledge that the application of an absolutely ecologically harmless aqueous solution enriched by molecular hydrogen and the use of limnetic algae confirmed the suitability of the innovative method for obtaining of nano gold from the concentrate. From the achieved research results significantly more effective kinetics is evident in the case of activated algae. Nanoparticles of gold obtained by the mentioned procedure can have important practical utilization, such as accelerating of the decomposition of dangerous substances or neutralizing pollutants in contaminated water, soil, and air. Simultaneously, obtaining of gold nanoparticles would also be beneficial for removing algae from the aquatic environment, where they are very dangerous for all living organisms.

Squaramide Organocatalyzed Addition of a Masked Acyl Cyanide to β-Nitrostyrenes.

A method for the squaramide-organocatalyzed enantioselective addition of a silyl-protected masked acyl cyanide (MAC) reagent to various β-nitrostyrenes is described. Reactions are carried out in a freezer and provide products cleanly and in high enantioselectivities at very low catalyst loadings. Adducts are then unmasked, providing various oxidation state 3 functional groups, thereby highlighting the utility of these MAC reagents and a new strategy for the preparation of β-amino acids.

Metal‐Free Synthesis of α‐Iminonitriles via Visible Light Photoredox Catalysis

AbstractA reaction of imidazo[1,2‐α]pyridine and Zhdankin reagent (IBA‐N3) is described for the synthesis of α‐iminonitriles via visible light photoredox catalysis. A series of substituted α‐iminonitriles were efficiently prepared in moderate to good yields under mild conditions. This transformation goes through a radical ring‐opening process to furnish the corresponding products. Notably, the reaction does not require toxic cyanide reagents, expensive metal photocatalysts and excessive oxidants.

Development of a Cyanide‐free and Scalable Route for the ADAMTS‐5 Inhibitor GLPG1972: Synthesis of an Advanced Key Chiral Intermediate

AbstractIn this study we report a mild, efficient, scalable, cyanide‐free and environmentally‐benign procedure for synthesizing 5,5‐disubstituted hydantoins starting from alkylnitriles and diethyl carbonate. Synthesis of 5,5‐disubstituted hydantoins is typically carried out under harsh conditions with transition metal catalysts that are not preferable from a sustainability perspective. This procedure illustrates an elegant cyanide‐free synthesis of cyclopropyl‐substituted 5,5‐hydantoins starting from alkylnitriles that circumvent cyanide reagents. This process holds great synthetic relevance owing to the great potential shown by 5,5‐cyclopropyl substituted hydantoins towards treating human osteoarthritis.

Metal‐Free, Oxidative Condensation of Heteroaryl‐ and Aryl Carbaldehydes towards Functionalized Carbonitriles

AbstractFunctionalization of pyridines with the carbonitrile group for advanced cyclization reactions routinely incorporates metals, toxic oxidants, and cyanide reagents, often in linear synthetic sequences. Motivated by the strategic need of a heteroaryl carbonitrile synthon for further elaboration, we disclose an efficient, metal‐free, one‐pot reaction sequence that uses ammonium acetate as the nitrogen source and bis‐acetoxyiodobenzene as the oxidant with low loadings. The developed method tolerates a diverse substrate scope including heteroaryl, aryl, and alkyl substrates with similar efficiency and expands the practitioner's reaction. Method development, optimization, substrate scope, preliminary mechanistic observations, competition experiments, and a scale up reaction are delineated herein.

Synthesis of (2-Nitro-1-AfAlemphenylethyl)malononitriles by Michael Addition of Masked Acyl Cyanides to Nitroalkenes

AbstractA highly efficient method has been developed for the synthesis of (2-nitro-1-phenylethyl)malononitriles through a Michael addition reaction between substituted nitroolefins and masked acyl cyanide reagents, serving as carbon monoxide equivalents. Under mild conditions, the reaction took place with excellent yields (90–98%), providing a short entry into a series of the title compounds in a scalable fashion. An asymmetric version of this reaction has also been briefly explored.

Photoinduced Etherification of Less-Strained Cycloketoxime Esters Enabled by C–C Bond Cleavage

We report a general, scalable, and convenient photochemical process for diversities of distal oxygenated nitriles from corresponding less-strained ketoxime esters allowing one-step introductions of ether and cyano groups, which avoids the utilization of toxic cyanide reagents. A wide range of ketoxime esters involving five-membered to eight-membered cycloketoxime esters and linear ketoxime esters participate smoothly under operately simple and mild conditions, affording structurally variable ring-opening products.

RECENT ADVANCES IN CYANATION REACTIONS†

Transformations involving structurally complex molecules, natural products and representative molecules are extremely important to obtain key reaction intermediates, in addition to accessing molecules with bioactive properties. The development of cyanation methodologies in those molecules becomes important, because nitriles are versatile and important building blocks in organic synthesis. They can be converted into other organic functions, including amines, alcohols, α-amino acids and various carbonyl compounds and can therefore become relevant synthetic intermediates. Recent studies show new and intriguing asymmetric cyanation protocols or reagents as those that use electrophilic cyanide source, metal- and oxidant-free or avoid the use of toxic cyanide reagents. Photoredox catalysis emerges as a relevant approach from the point of view of green and sustainable chemistry; usually provides access to the versatile skeleton of α-aminonitriles that among their various modes of reactivity and provide access to reactive iminium ion. Thus, this perspective aims to highlight these impressive advances as well as to show their main advantages and applications

Nickel-Catalyzed Deaminative Cyanation: Nitriles and One-Carbon Homologation from Alkyl Amines.

A nickel-catalyzed deaminative cyanation of Katritzky pyridinium salts has been developed. When it is coupled with formation of the pyridinium salt from primary amines, this method enables alkyl amines to be converted to alkyl nitriles. A less toxic cyanide reagent, Zn(CN)2, is utilized, and diverse functional groups and heterocycles are tolerated. The method also enables a one-carbon homologation of alkyl amines via reduction of the nitrile products, in addition to many other potential transformations of the versatile nitrile group.

Palladium-Catalyzed Nucleophilic Isocyanation for the Synthesis of α-Aryl-α-Isocyanoacetoamide Derivatives

Abstract α-Aryl-α-isocyanoacetoamide derivatives were synthesized through palladium-catalyzed nucleophilic isocyanation. Diethylphosphates derived from N,N-disubstituted mandelamide derivatives reacted with trimethylsilyl cyanide in the presence of a catalytic amount of Pd(OAC)2 to afford the titled isonitriles (13 examples) in moderate to high yield. The silyl cyanopalladate complex formed in situ was a proposed catalyst, which behaved as a Lewis acid promoting elimination of the phosphate group and also the N-nucleophilic cyanide reagent. The isocyanation was applied to a gram-scale reaction with 0.2 mol% of the catalyst. The obtained isocyanoacetoamide was employable for the further transformation into the trisubstituted oxazole without any purification procedure. DFT calculation suggested that the neighboring group effect of the carbonyl moiety in the substrate amide group assisted the elimination of phosphate and stabilized the carbocation intermediate. A plausible reaction mechanism of the isocyanation is also described.

Integrated Flow Synthesis of α-Amino Acids by In Situ Generation of Aldimines and Subsequent Electrochemical Carboxylation.

The synthesis of α-amino acids was carried out in a continuous flow system. In this system, aldimines were efficiently generated in situ via the dehydration-condensation of aldehydes with anilines in a desiccant bed column filled with 4 Å molecular sieves desiccant, followed by reaction with CO2 in an electrochemical flow microreactor to afford the α-amino acids in high to moderate yields. The present system can provide α-amino acids without using stoichiometric amounts of metal reagents or highly toxic cyanide reagents.

A new synthetic route for the preparation of pregabalin

We reported the synthesis of (S)-pregabalin in a five-step sequence with 20% overall yield. As a modification of the previously developed route, a Michael addition between CH3NO2 and chiral oxaoxazolidinone was employed as a key operation for introducing the methyleneamino group, which allowed avoiding the use of toxic cyanide reagent and led to enantiomerically pure product (>99% ee) after the recrystallization in appropriate solvent.

Comparative evaluation of compressive and flexural strength, fluoride release and bacterial adhesion of GIC modified with CPP-ACP, bioactive glass, chitosan and MDPB.

Background. This study evaluated the incorporation of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), calcium sodium phosphosilicate bioactive glass (BAG), chitosan (CH), and methacryloyloxydodecylpyridinium bromide (MDPB) on the compressive and flexural strength, fluoride (F‒ ) release, and bacterial adhesion of conventional glass-ionomer cement (C-GIC). Methods. Modifications were implemented by adding CPP-ACP, BAG, and CH to the glass powder, while MDPB-GIC was prepared by incorporating MDPB to the liquid of C-GIC. Custom-made molds were used for specimen preparation. Compressive and flexural strengths were evaluated using a universal testing machine. F‒ release was calculated with Erichrome cyanide reagent, using UV-spectrophotometry, at two time intervals of 24 hours and seven days. For bacterial adhesion, the test specimens were exposed to the bacterial suspension of Streptococcus mutans and Lactobacillus acidophilus for 4 hours, and the adherent bacteria were quantified using colorimetry as the optical density (OD). Results. The incorporation of MDPB increased the flexural strength of C-GIC, with no effect on its compressive strength. CH significantly improved the compressive and flexural strength; modifications with CPP-ACP, BAG, and MDPB significantly improved the flexural strength of C-GIC. While MDPB-GIC released significantly higher F‒ at 24 hours, CPP-ACP- and BAG-modified GICs were comparable to C-GIC on day 7. C-GIC exhibited the highest bacterial adhesion, and MDPB-GIC showed the least. The data were analyzed with one-way (ANOVA), and pairwise comparisons were made with Tukey HSD tests. Conclusion. Hence, it can be concluded that the incorporation of CPP-ACP, BAG, and CH improved the mechanical properties of C-GIC, whereas MDPB improved the resistance of C-GIC to bacterial adhesion.

Electrochemically promoted oxidative α-cyanation of tertiary and secondary amines using cheap AIBN.

The electrochemical α-cyanation of tertiary and secondary amines has been developed by using a cheap cyanide reagent, azobisisobutyronitrile (AIBN). The CN radical, generated through n-Bu4NBr-meidated electrochemical oxidation, participates in a novel α-cyanation reaction under exogenous oxidant-free conditions.

Gold(I)-MIC Complexes as a Highly Effective Catalyst for the Cyanosilylation of Carbonyl Compounds Under Solvent-Free Condition

Herein, we report the gold(I)-MIC complexes (1-3), bearing mesoionic carbene (MIC) ligands were synthesized. The catalytic activities of these gold(I)-MIC complexes were found to be highly effective catalysts for cyanosilylation of various aldehydes under solvent-free conditions using TMSCN (trimethylsilyl cyanide). The cyano group transfer from TMSCN to aldehydes proceeds at room temperature in the presence of only 5 mol % of Au(I)-MIC catalysts (1-3), to produce value-added cyanohydrin trimethylsilyl ethers in very good to excellent yields within 6 h, from various aldehydes through cyanosilylation process by using trimethylsilyl cyanide reagent at room temperature under solvent-free condition. These reaction conditions are extremely mild and simple and tolerate various functional groups.

Continuous Flow Synthesis of N-Phenylphenylglycine By Dehydration and Electrochemical Carboxylation

α-Amino acids and their derivatives are important and essential resources for human life such as foods, medical drugs, cosmetics and so on. The classical Strecker α-amino acids synthesis is a longstanding method although this classical method requires highly toxic cyanide reagents as the carbon source and these regents are unfavorable from the viewpoint of green chemistry. Carbon dioxide, on the other hand, would also be an abundant and favorable carbon source. There are several examples of synthesis of α-amino acids by direct carboxylation of imines with carbon dioxide. Because of chemical stability of carbon dioxide, this direct carboxylation requires stoichiometric quantities of hard to handle reagents such as magnesium metal and organotins under severe or harsh reaction conditions.In this context, electrochemical carboxylation represents an attractive alternative to conventional chemical carboxylation methods because it is possible to readily generate highly reactive carbon nucleophiles that immediately react with carbon dioxide without handling sensitive, expensive, and toxic reagent. However, metal ions derived from sacrificial anode such as magnesium and aluminium anodes are generally required to stabilize the unstable carboxylate ions.A flow microreactor enables fast generation and consumption of the unstable species. Therefore, it is attractive reaction system for electrochemical carboxylation involving unstable carboxylate ions without sacrificial anodes. Moreover, the electrochemical synthesis with a flow microreactor offers operational advantages over batch processes.Under these backgrounds, we have demonstrated the electrochemical carboxylation of in situ generated imines in a continuous flow system. The present method enables an efficient synthesis for N-phenylphenylglycine derivatives using easily available aldehydes, amines, and CO2 without the use of toxic metal reagents and sacrificial anode.As shown in Figure 1, the imine was smoothly generated from aldehyde and amine by dehydration using MS4A desiccant in a flow operation, and then reacted with carbon dioxide in the electrochemical flow microreactor to afford N-phenylphenylglycine derivatives with high to moderate yields. Figure 1

Novel Commercial Scale Synthetic Approach for 5-Cyanoindole: A Potential Intermediate for Vilazodone Hydrochloride, an Antidepressant Drug

Present work describes the synthesis of 5-cyanoindole, a common intermediate used in various synthetic route of the antidepressant vilazodone hydrochloride. The protocol is both robust and commercially viable, utilizing readily available and low-cost materials and the isomers are environmental friendly than previously reported routes through its evading use of cyanide reagents and heavy metals.

Ruthenium‐Catalyzed Direct Transformation of Alkenyl Oximes to 5‐Cyanated Isoxazolines: A Cascade Approach Based on Non‐Stabilized Radical Intermediate

A ruthenium‐catalyzed ammoxidation of alkenyl oximes under mild and neutural condtions is described. In this method, tert‐butyl nitrite plays a dual role, acting as an oxidant as well as a nitrogen source. This reaction avoids using any toxic radical initiators or cyanide reagents. This convenient and practical method offers an easy access to 5‐cyanated isoxazolines in good to high yields, and shows good functional group tolerance and high efficiency. It is rather remarkable that this new reaction provides a strategically distinct approach based on non‐stabilized radical intermediate and constructs C–O and C≡N triple bonds in a single‐step. Moreover, the difunctionalization of unactivated olefins bearing oximes has been realized.

Cu-Catalyzed Redox-Neutral Ring Cleavage of Cycloketone O-Acyl Oximes: Chemodivergent Access to Distal Oxygenated Nitriles.

A chemodivergent copper-catalyzed ring opening of cycloketone oximes via radical-mediated C-C bond cleavage under redox-neutral conditions is described. This method allows the divergent synthesis of γ- and δ-acyloxylated, alkoxylated, and hydroxylated nitriles while avoiding the use of toxic cyanide reagents. Moreover, these reactions proceed under very mild conditions with good functional group tolerance. Notably, ring-opening reactions of the less-strained substrate cyclopentanone oxime also proceeded well under the established conditions.

Synthesis of Functionalized Nitriles by Microwave-Promoted Fragmentations of Cyclic Iminyl Radicals.

The synthesis of functionalized nitriles via microwave-promoted radical fragmentations of cyclic O-phenyl oxime ethers is reported. A variety of radical traps can be employed, permitting the generation of diverse adducts via C-O, C-C, C-N, or C-X bond formation. Other salient features include a simple and practical protocol, very short reaction times, and the avoidance of metal catalysts and toxic cyanide reagents. The utility of this method is demonstrated by the ring-distortion of a steroid-derived substrate.