Triarylmethanes Research Articles

HFIP-Mediated Dual C(Ar)-Alkylation Process Towards the Regioselective Synthesis of Triarylmethanes (TRAMs).

The distinct roles of different chemical species are essential for the discovery of novel chemical transformations in organic synthesis. Here, we have designed a potential strategy for the synthesis of triarylmethanes (TRAMs) using the dual C(aryl)-alkylation process. This protocol was influenced by 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a pivotal reagent and proceeds through the selective para C-H functionalization method. The described approach has been proven to be highly efficient in terms of substrate scope with excellent functional group tolerance and gram scale synthesis of the desired product with 90 % yield. The recyclability and reusability of HFIP has enhanced the feasibility of this protocol towards the sustainable synthesis of TRAMs.

Formation of Bis‐indolylmethanes from Symmetrical Triarylmethanes via Brønsted Acid Catalyzed C−C Bond Breaking Reaction

AbstractAn alternative approach to synthesize bis‐indolylmethanes (BIMs) via a unique p‐toluenesulfonic acid (PTSA) catalyzed dual Csp3−Csp2 bond‐breaking reaction has been reported here. In the reported protocol, 1,3,5‐trimethoxybenzene (TMB), an electron‐rich and sterically bulky arene, acts as a carbon‐based leaving group which can be recovered after the completion of the reaction. In this process, several BIMs of various indole derivatives can be synthesized from symmetrical triarylmethanes (TRAMs) containing bis‐TMB motifs. By modifying the reaction conditions, we could control the sequential bond cleavage of two Csp3−Csp2 bonds in starting TRAM.

B(OH)3‐Catalyzed Dual Friedel‐Crafts Type Reaction of Anilines and Aldehydes to Access Di‐ or Triarylmethanes (TRAMs)

AbstractThe catalytic influences of boric acid have been introduced on dual Friedel‐Crafts reaction between arylamines and aldehydes to install the Csp3‐center that leads to the formation of di‐ or tri‐substituted methanes. The described reaction conditions have directed the transformation to favor the para‐para substitution pattern to deliver the major products rather than the corresponding ortho‐para functionalization process. The devised transformation was examined by DFT calculation, which shows the favorable activation energy of transition states (TS) for the generation of highly substituted molecular scaffolds. The method was applicable over diversely substituted aldehydes and arylamines to afford the final products in excellent yields (60‐92 %) and selectivity. The proposed mechanism is supported by suitable control experiments, GC‐MS studies, and DFT calculations.

Gram-Scale Synthesis of Substituted Triarylmethanes

AbstractA high-yield, open-vessel route for the facile-operational, gram-scale synthesis of functionalized triarylmethanes (TRAMs) is described­ via silica-coated magnetic nanoparticles of modified polyphosphoric­ acid (NiFe2O4@SiO2-PPA)-mediated intermolecular Friedel­–Crafts reaction of substituted aryl aldehydes with 2 equivalents of oxygenated arenes under environmentally friendly reaction conditions. Among the overall reaction process, only water was generated as the by-product. Various reaction conditions are investigated for efficient transformation.

Dehydrative Substitution Reaction in Water for the Preparation of Unsymmetrically Substituted Triarylmethanes: Synthesis, Aggregation-Enhanced Emission, and Mechanofluorochromism.

Water as a reaction media in chemical transformations has several advantages in terms of safety and non-toxicity. However, dehydrative substitution reaction in water is a highly challenging operation. In this paper, we have reported a sulfamic acid-mediated dehydrative substitution reaction of benzofuryl alcohols with several nucleophiles in water towards the scalable, easily isolable, synthesis of unsymmetrically substituted triarylmethanes (TRAMs) in good to excellent yields (up to 92 %). Moreover, we have demonstrated that rationally designed propellor-shaped triarylmethanes promote aggregation-induced emission (AIE) through restricted intramolecular rotation with irreversible mechanoflurochromic property.

Remote Functionalization of 8‐Substituted Quinolines with para‐Quinone Methides: Access to Unsymmetrical Tri(hetero)arylmethanes

AbstractA C(5)−H remote functionalization of 8‐aminoquinoline derivatives with para‐quinone methides, affording direct access to unsymmetrical tri(hetero)arylmethanes in 69–96 % yield is described. This method provides diverse tri(hetero)arylmethanes with a broad scope and in a regioselective manner. The transformation works well with electron‐rich and electron‐deficient substrates.

Solvent-free 1,6-conjugate arylation of para-quinone methides: A greener approach to unsymmetrical triarylmethanes

A highly efficient arylation of para-quinone methides (p-QMs) with N,N-dimethylaniline under solvent free condition has been developed, which proceeded via a para-toluenesulfonic acid (TsOH)-promoted 1,6-conjugated addition pathway. This methodology provided a green and sustainable methodology to construct various novel unsymmetrical triarylmethanes (TAMs) with the advantages of good functional group tolerance, scalability, and regioselectivity.

Synthesis and Evaluation of Anticancer Activity of Pyrazolone Appended Triarylmethanes (TRAMs)

AbstractThe present work describes the design, synthesis, and evaluation of the anticancer properties of pyrazolone ring appended triarylmethanes by the condensation of diarylmethanols with pyrazolone in presence of a catalytic amount of p‐TSA catalyst. The use of an inexpensive catalyst and accessing the desired product in good yields within a short span are the merits associated with this protocol. Furthermore, the in‐silico, as well as in‐vitro analysis and molecular docking of the designed molecules, were performed followed by their anticancer activity evaluation against cancer cell lines like MCF7, MDA‐MB‐231, HeLa, and DU‐145. Few of the synthesized molecules demonstrated significant anticancer activity and could provide a new direction in the development of anti‐cancer molecules.

Sulfonated Tetraphenylethylene-Based Hypercrosslinked Polymer as a Heterogeneous Catalyst for the Synthesis of Symmetrical Triarylmethanes via a Dual C–C Bond-Cleaving Path

AbstractA sulfonic acid functionalized tetraphenylethylene-based hypercrosslinked polymer (THP-SO3H) with a well-developed porous network and accessible sulfonic acid sites was synthesized and characterized by different analytical techniques. The catalytic prowess of the synthesized material THP-SO3H was investigated in a challenging dual C–C bond-breaking reaction for the synthesis of symmetrical triarylmethanes (TRAMs) in high yield. The scope of the developed metal-free method was also explored with a wide variety of substrates. The organocatalyst can be easily recovered by filtration and reused up to five consecutive cycles without substantial loss in its catalytic efficacy.

Synthesis of new functionalized triarylmethanes via Suzuki cross-coupling and Heck-type vinylation reactions

A novel class of triarylmethanes (TRAMs) containing one or two biaryl moieties was synthesized efficiently through the Pd(PPh 3 ) 4 -catalyzed Suzuki–Miyaura cross-coupling reaction of brominated TRAMs with arylboronic acid derivatives. We also demonstrate that brominated TRAMs can be efficiently functionalized via a one-pot, two-step Pd-catalyzed Heck-type process. This protocol provides convenient access to diverse vinylated TRAMs that are generally not obtained by using the common synthetic methods for TRAMs.

Mild and Metal-Free Protocol toward the Synthesis of Triarylmethanes by Reactions of (Hetero)Arylboronic Acids and ortho-Hydroxyarylaldehydes.

Herein, we have reported a metal-free, mild, and novel protocol for the synthesis of various triarylmethanes (TRAMs) in moderate to good yields via the reactions of aryl boronic acids and ortho-hydroxyarylaldehydes in the presence of stoichiometric amounts of Et3N in dichloroethane at 80 °C. Additionally, the synthetic utilities of few synthesized TRAMs were proven by carrying out bromination on the -OH-containing aryl part and followed by functionalization of bromine through a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction with arylboronic acids in good yields. The -OH group was also alkylated and arylated through simple alkylation and Chan-Lam reaction, respectively.

Advances in The Catalytic Synthesis of Triarylmethanes (TRAMs)

The last couple of decades has witnessed an incredible development in the progress of catalytic creation of triarylmethane (TRAM) motif. The broad‐spectrum applications of TRAMs in domains like medicinal chemistry, pharmacology, dyes, and functional materials has urged scientists to invent their efficient synthetic strategies. Herein, we have attempted to comprehensively document the catalytic methodologies for the synthesis of triarylmethanes which will satiate the anticipations of the readers who are looking for an update and stimulate the researches for further development.

Iron‐Catalyzed Tandem C‐N and C–C bond Cleavage in Diaryl Methanamines: Use of Electron‐Rich Arenes as Leaving Group to Generate Triaryl Methanes

AbstractA facile FeCl3 catalyzed tandem C−N and C−C bond cleavage in N‐protected diaryl methanamines has been studied where the C−C bond cleavage, interestingly, results in the release of electron‐rich and sterically bulky arenes such as 1,3,5‐trimethoxybenzene or 3,5‐dimethoxytoluene. The tandem bond cleavage reaction generates triaryl methanes in mild conditions under air atmosphere. We found success in isolating the intermediate, formed through the preliminary C−N bond cleavage, and then converted the isolated intermediate to the final triaryl methanes by affecting the subsequent C−C bond cleavage. Several nucleophiles such as indoles, furans, 4‐methoxythiophenol and 1,3‐dimethoxybenzene were found effective under Lewis acidic conditions to cause the unusual yet facile tandem bond cleavage reaction in the diaryl methanamines. Use of electron‐rich and sterically bulky arenes as leaving groups in the present work highlights an innovative concept, which may potentially open up parallel avenues in organic synthesis.

Palladium-Catalyzed Triarylation of sp3 C-H Bonds in Heteroarylmethanes: Synthesis of Triaryl(heteroaryl)methanes.

A straightforward method for the palladium-catalyzed triarylation of heteroarylmethanes at the methyl group has been developed. The reaction works with a variety of aryl halides, enabling the rapid synthesis of triaryl(heteroaryl)methanes in moderate to excellent yields.

Transition metal-free direct dehydrogenative arylation of activated C(sp3)-H bonds: synthetic ambit and DFT reactivity predictions.

A transition metal-free dehydrogenative method for the direct mono-arylation of a wide range of activated C(sp3)-H bonds has been developed. This operationally simple and environmentally friendly aerobic arylation uses tert-BuOK as the base and nitroarenes as electrophiles to prepare up to gram quantities of structurally diverse sets (>60 examples) of α-arylated esters, amides, nitriles, sulfones and triaryl methanes. DFT calculations provided a predictive model, which states that substrates containing a C(sp3)-H bond with a sufficiently low pK a value should readily undergo arylation. The DFT prediction was confirmed through experimental testing of nearly a dozen substrates containing activated C(sp3)-H bonds. This arylation method was also used in a one-pot protocol to synthesize over twenty compounds containing all-carbon quaternary centers.

Palladium-catalysed synthesis of triaryl(heteroaryl)methanes

Tetraarylmethane derivatives are desirable for a variety of applications, but difficult to access with modern C–C bond-forming reactions. Here we report a straightforward method for palladium-catalysed arylation of aryl(heteroaryl)methanes and diaryl(heteroaryl)methanes with aryl chlorides. This reaction enables introduction of various aryl groups to construct triaryl(heteroaryl)methanes via a C–H functionalization in good to excellent yield, and represents the first step towards a general transition metal catalysed synthesis of tetraarylmethanes.

Catalyst free, three-component approach for unsymmetrical triarylmethanes (TRAMs)

An efficient catalyst free, three-component, cascade approach has been designed and developed for the rapid assembly of unsymmetrical triarylmethane framework. The strategy employed aromatic aldehydes, Grignard reagents, and neutral aromatics as reaction partners, under simple thermal conditions. This process affords very broad scope for all three partners as it is performed in the absence of any external additives.

Thiophene containing trisubstituted methanes [TRSMs] as identified lead against Mycobacterium tuberculosis

Triarylmethanes (TRAMs) and thiophene containing trisubstituted methanes (TRSMs) have been reported by us, having potential against Mycobacterium tuberculosis and Mycobacterium fortuitum strains, respectively. Further, extension through synthesis and biological evaluation of novel TRSMs resulted into an identified lead 36 (S006-830) [(diisopropyl-(2-{4-[(4-methoxy-phenyl)- thiophen-2-yl-methyl]-phenoxy}-ethyl)-amine)] with MIC: 1.33 mg/L, non-toxic against Vero C-1008 cell line with selectivity index >10, ex vivo efficacy equivalent to first line TB drugs-isoniazid (INH), rifampicin (RFM) and pyrazinamide (PZA) in the mouse and human macrophages, and lung CFU count of 2.2 × 107 (approximately 15 fold lesser than untreated mice, 31 × 107) with efficacies comparable to ethambutol (EMB) (1.27 × 107) and PZA (1.9 × 107). Further, S006-830 also showed potent bactericidal activity against multi-drug resistant and single-drug resistant clinical isolates of M. tuberculosis.

ChemInform Abstract: Synthetic Methodologies of Achiral Diarylmethanols, Diaryl and Triarylmethanes (TRAMs) and Medicinal Properties of Diaryl and Triarylmethanes — an Overview

AbstractReview: [223 refs.

Brönsted acid ionic liquids catalyzed Friedel–Crafts Alkylations of electron-rich arenes with aldehydes

Triarylmethanes (TRAMs) and diarylalkanes (DIAAs) are valuable intermediates with wide applications in many fields. TRAMs are usually obtained from the acid-catalysed bisarylation of activated aryl aldehydes. However, the synthesis poses many problems, such as harsh reaction conditions, and the disposal of the excess solvents and/or toxic metal waste. In this study, some functionalized ionic liquids including Brönsted acid ionic liquids (BAILs) and traditional ionic liquids were designed and synthesized. BAILs catalyzed Friedel–Crafts (F–C) alkylation was applied in this specific reaction for the first time. And the BAILs showed bifunctional properties acting as catalyst and solvent. Research shows that BAILs can be used for catalyzing F–C alkylations of electron-rich arenes with aromatic or aliphatic aldehydes successfully under mild reaction conditions. Furthermore, BAILs containing triflic anion has higher activity than other BAILs and traditional ionic liquids. [HSO3-pmim][OTf] gets the highest yields in the presence of 20mol% of BAILs at 40°C to give the corresponding TRAMs derivatives. After five cycles, the yields remain about 93–97%. Finally, according to IR spectrum and the experimental validation, the aromatic electrophilic substitution reaction was considered to be the possible catalysis mechanisms.