Search Results (28)

One of the key strategies in drug design involves modifying molecular scaffolds with specific chemical groups, or side chains, to enhance biological and physicochemical properties. These modifications can strengthen interactions with biological targets or improve pharmacokinetic and physicochemical characteristics, factors that are critical in transforming a compound into a viable drug candidate. In this overview, we focus on the presence of trifluoromethyl and trifluoromethoxy groups on different molecules, highlighting their relevance and impact in medicinal chemistry. The discussion and future perspectives in the field are based on a comprehensive review of current literature, with data sourced mainly from SciFinder and PubMed. Full article

The unprecedented use of ethynyl trifluoromethyl sulfide (CF₃S–C≡CH) as a synthetically useful building block has been described for the first time. It was reacted with various aromatic and aliphatic azides under copper-catalyzed conditions to yield a novel class of 1,4-disubstituted triazoles bearing the SCF₃ group (15 examples, up to 86% yield). Full article

3-Chalcogenylindoles serve as crucial building blocks in organic synthesis and pharmaceutical chemistry. Herein, we describe a simple and general synthesis of 3-chalcogenylindoles through the direct C–H chalcogenation of indoles using N-selenophthalimide and N-sulfenylsuccinimide as chalcogenation reagents in the presence of CuBr₂ as the catalyst. The reactions were carried out in CH₂Cl₂ at room temperature under an air atmosphere with a low loading of catalyst, and a wide range of 3-selenylindoles and 3-thioindoles were obtained in good yields. Various functionalities, namely, methyl, methoxy, halo, ester, cyano, trifluoromethyl, and formyl groups on indoles, have shown amenability to the developed reaction. A mechanism involving the activation of the chalcogenation agent through CuBr₂ coordination with the amide carbonyl group is proposed. Full article

Area-selective atomic layer deposition (AS-ALD) is a technique utilized for the fabrication of patterned thin films in the semiconductor industry due to its capability to produce uniform and conformal structures with control over thickness at the atomic scale level. In AS-ALD, surfaces are functionalized such that only specific locations exhibit ALD growth, thus leading to spatial selectivity. Self-assembled monolayers (SAMs) are commonly used as ALD inhibiting agents for AS-ALD. However, the choice of organic molecules as viable options for AS-ALD remains limited and the precise effects of ALD nucleation and exposure to ALD conditions on the structure of SAMs is yet to be fully understood. In this work, we investigate the potential of small molecule carboxylates as ALD inhibitors, namely benzoic acid and two of its derivatives, 4-trifluoromethyl benzoic acid (TBA), and 3,5-Bis (trifluoromethyl)benzoic acid (BTBA) and demonstrate that monolayers of all three molecules are viable options for applications in ALD blocking. We find that the fluorinated SAMs are better ALD inhibitors; however, this property arises not from the hydrophobicity but the coordination chemistry of the SAM. Using nanoscale infrared spectroscopy, we probe the buried monolayer interface to demonstrate that the distribution of carboxylate coordination states and their evolution is correlated with ALD growth, highlighting the importance of the interfacial chemistry in optimizing and assessing ALD inhibitors. Full article

Oxazoles are important five-membered heterocycles that contain both nitrogen and oxygen atoms. Due to their wide range of biological activities, many oxazoles demonstrate potential for extensive application in various fields, including medicinal chemistry. Trifluoromethyl carbinol, an important pharmacophore, contains both trifluoromethyl and hydroxyl groups and is common in molecules with important biological activities. Constructing oxazoles that contain a trifluoromethyl carbinol unit is undoubtedly important and valuable for expanding the chemical space in drug discovery. In this study, a simple and efficient method was developed for the synthesis of oxazoles containing a CF₃-substituted alcohol unit via the tandem cycloisomerization/hydroxyalkylation of N-propargylamides with trifluoropyruvates through a rational Lewis acid catalytic mechanism. This Zn(OTf)₂-catalyzed synthetic protocol is operationally simple and provides a series of oxazoles in moderate to good yields. The protocol demonstrates broad substrate scope, high functional group tolerance, and high atom economy and can achieve gram-level reactions, indicating the strong possibility of its practical application. Full article

Fluorinated organic compounds have demonstrated remarkable utility in medicinal chemistry due to their enhanced metabolic stability and potent therapeutic efficacy. Several examples exist of fluorinated non-steroidal anti-inflammatory drugs (NSAIDs), including diflunisal, flurbiprofen, and trifluoromethylated pyrazoles celecoxib and mavacoxib. These trifluoromethylated pyrazoles, which are most commonly constructed through the cyclocondensation of a trifluorinated 1,3-dicarbonyl and an aryl hydrazine, are also found in numerous other drug candidates. Here, we interrogate the effects of solvents and the presence of Brønsted or Lewis acid catalysts on catalyzing this process. We highlight the utility of benchtop ¹⁹F NMR spectroscopy in enabling the real-time quantification of reaction progress and the identification of fluorinated species present in crude reaction mixtures without the need for cost-prohibitive deuterated solvents. Ultimately, we find that the reaction solvent has the greatest impact on the rate and product yield, and also found that the relationship between the keto-enol equilibrium of the dicarbonyl starting material pyrazole formation rate is highly solvent-dependent. More broadly, we describe the optimization of the yield and kinetics of trifluoromethylpyrazole formation in the synthesis of celecoxib and mavacoxib, which is made possible through high-throughput reaction screening on benchtop NMR. Full article

Polymeric optical films with light colors, good optical transparency and high thermal resistance have gained increasing attention in advanced optoelectronic areas in recent years. However, it is somewhat inter-conflicting for achieving the good optical properties to the conventional thermal resistant polymers, such as the standard aromatic polyimide (PI) films, which are well known for the excellent combined properties and also the deep colors. In this work, a series of wholly aromatic PI films were prepared via the polycondensation chemistry of one fluorene-containing dianhydride, 9,9-bis(3,4-dicarboxyphenyl)fluorene dianhydride (FDAn) and several aromatic diamines with amide linkages in the main chain, including 9,9-bis [4-(4-aminobenzamide)phenyl]fluorene (FDAADA), 2,2′-bis(trifluoromethyl)-4,4′-bis[4-(4-aminobenzamide)] biphenyl (ABTFMB), and 2,2′-bis(trifluoromethyl)-4,4′-bis[4-(4-amino-3-methyl)benzamide] biphenyl (MABTFMB). The derived FLPI-1 (FDAn-FDAADA), FLPI-2 (FDAn-ABTFMB) and FLPI-3 (FDAn-MABTFMB) resins showed good solubility in the polar aprotic solvents, such as N-methyl-2-pyrrolidone (NMP), N,N-dimethylacetamide (DMAc) and dimethyl sulfoxide (DMSO). The solution-processing FDAn-PI films exhibited good optical transmittance over 80.0% at a wavelength of 500 nm (T₅₀₀), yellow indices (b*) in the range of 1.01–5.20, and haze values lower than 1.0%. In addition, the FDAn-PI films showed low optical retardance with optical retardation (R_th) values in the range of 31.7–390.6 nm. At the same time, the FDAn-PI films exhibited extremely high glass transition temperatures (T_g) over 420 °C according to dynamic mechanical analysis (DMA) tests. The FDAn-PI films showed good dimensional stability at elevated temperatures with linear coefficients of thermal expansion (CTE) in the range of (31.8–45.8) × 10⁻⁶/K. Full article

Conjugated diyne derivatives are important scaffolds in modern organic synthetic chemistry. Using the Glaser reaction involves the coupling of terminal alkynes which can efficiently produce conjugated diyne derivatives, while the use of a stoichiometric amount of copper salts, strong inorganic base, and excess oxidants is generally needed. Developing an environmentally friendly and effective method for the construction of symmetrical 1,3-diynes compounds by Glaser coupling is still highly desirable. In this study, we present an economical method for the production of symmetric diynes starting from various terminal acetylenes in a Glaser reaction. A simple and practical bis-N-heterocyclic carbene ligand has been introduced as efficient ligands for the Cu-catalyzed Glaser reaction. High product yields were obtained at 100 °C for a variety of substrates including aliphatic and aromatic terminal alkynes and differently substituted terminal alkynes including the highly sterically hindered substrate 2-methoxy ethynylbenzene or 2-trifluoromethyl ethynylbenzene and a series of functional groups, such as trifluoromethyl group, ester group, carboxyl group, and nitrile group. The established protocol is carried out in air under base-free condition and is operationally simple. These research work suggest that bis-N-heterocyclic carbene could also an appealing ligand for Glaser reaction and provide a reference for the preparation of symmetric 1,3-diynes in industrial filed. Full article

The trifluoromethyl group is widely recognized for its significant role in the fields of medicinal chemistry and material science due to its unique electronic and steric properties that can alter various physiochemical properties of the parent molecule, such as lipophilicity, acidity, and hydrogen bonding capabilities. Compared to the well-established C-trifluoromethylation, N-trifluoromethylation has received lesser attention. Considering the extensive contribution of nitrogen to drug molecules, it is predicted that constructing N-trifluoromethyl (N-CF₃) motifs will be of great significance in pharmaceutical and agrochemical industries. This review is mainly concerned with the synthesis of heterocycles containing this motif. In three-membered heterocycles containing the N-CF₃ motif, the existing literature mostly demonstrated the synthetic strategy, as it does for four- and larger-membered heterocycles. Certain structures, such as oxaziridines, could serve as an oxidant or building blocks in organic synthesis. In five-membered heterocycles, it has been reported that N-CF₃ azoles showed a higher lipophilicity and a latent increased metabolic stability and Caco-2-permeability compared with their N-CH₃ counterparts, illustrating the potential of the N-CF₃ motif. Various N-CF₃ analogues of drugs or bioactive molecules, such as sildenafil analogue, have been obtained. In general, the N-CF₃ motif is developing and has great potential in bioactive molecules or materials. Give the recent development in this motif, it is foreseeable that its synthesis methods and applications will become more and more extensive. In this paper, we present an overview of the synthesis of N-CF₃ heterocycles, categorized on the basis of the number of rings (three-, four-, five-, six- and larger-membered heterocycles), and focus on the five-membered heterocycles containing the N-CF₃ group. Full article

Coordination polymers of transition metal ions are fascinating and important to coordination chemistry. One of the ligands known to form particularly interesting coordination polymers is 3,3′,5,5′-tetramethyl-4,4′-bipyrazole (Me₄bpzH₂). Group 11 metal(I) ion coordination polymers, other than those of copper(I), are relatively easy to handle because of their low reactivity towards dioxygen and moisture. However, the known silver(I) coordination polymers often have poor solubility in common solvents and so cannot be easily analyzed in solution. By using a tetramethyl substituted bipyrazole ligand, we have synthesized more soluble silver(I) complexes that contain the trifluoromethyl group in the coordinated ions CF₃CO₂⁻ and CF₃SO₃⁻ in [Ag(CF₃CO₂)(Me₄bpzH₂)] and [Ag(CF₃SO₃)(Me₄bpzH₂)]. We determined both structures by single-crystal X-ray analysis at low temperatures and compared them in detail. Moreover, we investigated the solution behavior of these coordination polymers by ¹H-NMR, IR, Raman, UV–Vis spectroscopies, and their low-temperature, solid-state photoluminescence. The high-energy band at ~330 nm corresponded to ligand-centered (bipyrazole) fluorescence, and the low-energy band at ~400 nm to ligand-centered phosphorescence resulting from the heavy atom effect. Full article

Amino-[1,1′]-biphenyl-containing 3-aryl-[1,2,4]triazolo[4,3-c]quinazoline derivatives with fluorescent properties have been designed and synthesized. The type of annelation of the triazole ring to the pyrimidine one has been unambiguously confirmed by means of an X-ray diffraction (XRD) method; the molecules are non-planar, and the aryl substituents form the pincer-like conformation. The UV/Vis and photoluminescent properties of target compounds were investigated in two solvents of different polarities and in a solid state. The samples emit a broad range of wavelengths and display fluorescent quantum yields of up to 94% in toluene solutions. 5-(4’-Diphenylamino-[1,1′]-biphenyl-4-yl)-3-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[4,3-c]quinazoline exhibits the strongest emission in toluene and a solid state. Additionally, the solvatochromic properties were studied for the substituted [1,2,4]triazolo[4,3-c]quinazolines. Moreover, the changes in absorption and emission spectra have been demonstrated upon the addition of water to MeCN solutions, which confirms aggregate formation, and some samples were found to exhibit aggregation-induced emission enhancement. Further, the ability of triazoloquinazolines to detect trifluoroacetic acid has been analyzed; the presence of TFA induces changes in both absorption and emission spectra, and acidochromic behavvior was observed for some triazoloquinazoline compounds. Finally, electronic-structure calculations with the use of quantum-chemistry methods were performed for synthesized compounds. Full article

In materials (polymer) science and medicinal chemistry, heteroaromatic derivatives play the role of the central skeleton in development of novel devices and discovery of new drugs. On the other hand, (3-trifluoromethyl)phenyldiazirine (TPD) is a crucial chemical method for understanding biological processes such as ligand–receptor, nucleic acid–protein, lipid–protein, and protein–protein interactions. In particular, use of TPD has increased in recent materials science to create novel electric and polymer devices with comparative ease and reduced costs. Therefore, a combination of heteroaromatics and (3-trifluoromethyl)diazirine is a promising option for creating better materials and elucidating the unknown mechanisms of action of bioactive heteroaromatic compounds. In this review, a comprehensive synthesis of (3-trifluoromethyl)diazirine-substituted heteroaromatics is described. Full article

The development of diversity-oriented synthesis based on fluorine-containing building blocks has been one of the hot research fields in fluorine chemistry. β-CF₃-1,3-enynes, as one type of fluorine-containing building blocks, have attracted more attention in the last few years due to their distinct reactivity. Numerous value-added trifluoromethylated or non-fluorinated compounds which have biologically relevant structural motifs, such as O-, N-, and S-heterocycles, carboncycles, fused polycycles, and multifunctionalized allenes were synthesized from these fluorine-containing building blocks. This review summarizes the most significant developments in the area of synthesis of organofluorine compounds based on β-CF₃-1,3-enynes, providing a detailed overview of the current state of the art. Full article

Pyrazoles have potential applications in the agrochemical and medicinal chemistry industries as pesticides, anti-inflammatory medications, and antitumor drugs. Fluorinated fused-ring pyrazoles may also possess medicinally useful properties. Herein, we report the acid-catalyzed synthesis of a new tricyclic, trifluoromethylated indenopyrazole, 3-methyl-1-(4-(trifluoromethyl)phenyl)indeno[1,2-c]pyrazol-4(1H)-one, from 2-acetyl-1,3-indanedione and 4-trifluoromethylphenylhydrazine. This isomeric pyrazole was obtained in yields ranging from 4–24%. NMR spectroscopic characterization and elemental analysis support the structural assignment, identity, and purity of the product. Full article

Fluorochemistry is a field of tremendous developments and advances in several areas of science including materials, pharmaceuticals and agriculture. This makes the design and synthesis of fluorine-containing substances highly desirable research targets. The sub-area of synthetic perfluorinated chemistry proportionately attracts widespread interest by applying to all areas of chemistry including organic and inorganic. Particularly, the latter is much underdeveloped as metal complexes with perfluoroalkyl moieties are scarce, with the vast majority of perfluorinated analogs, of long known, halo and alkylated derivatives never having been synthesized. Focusing on the chemistry of trifluoromethyl group, which is the most important in the class of perfluoroalkyls, we set out to explore the possibility of synthesizing and completely characterizing a cyclohexadienyl metal complex. Upon utilizing a number of trifluorometylating reagents, we only arrived at an efficient preparation by the use of Morrison’s trifluormethylating reagent. As a result, the new, air- and moisture-sensitive complex (η⁵-C₆H₇)Fe(CO)₂CF₃, was prepared in 71% yield, using a nucleophilic iodo-for-trifluoromethyl substitution, and was completely characterized including by X-ray crystallography. Full article