Triethyl Orthoformate Research Articles

Design, Synthesis, Antibacterial, and Antifungal Evaluation of a New Series of Quinazoline - Thiazole and/or Quinazoline - Triazole Hybrids as Bioactive Heterocycles.

Herein, a one-pot reaction between cyclohexanone, thiourea, and 2,5-dimethoxybenzaldehyde allowed to prepare hexahydroquinazoline-2(1H)-thione4 firstly, which followed by reacting with hydrazine hydrate to produce the corresponding 2-hydrazinylhexahydroquinazoline 6. Interesting analogs of thiazolo[3,2-a]quinazoline 713 where obtained when hexahydroquinazoline-2(1H)-thione 4 reacted with 1,2-dibromoethane, chloroacetyl chloride, bromoacetic acid, bromoacetic acid/4-chlorobenzaldehyde, 2-bromopropionic acid, ethyl bromo cyanoacetate, and/or bromomalononitrile; respectively. While triazolo[4,3-a] quinazoline 14-16 were created when 2-hydrazinylhexahydroquinazoline 6 reacted with triethyl orthoformate, acetic anhydride, and carbon disulfide respectively. Numerous spectroscopy tests, including FT-IR, NMR (1H &13 C), and MS spectrum, proved all the newly produced analogs. Additionally, the new analogs were examined for their antibacterial and antifungal properties against Escherichia coli, Staphylococcus aureus, and Candida albicans. It was discovered that triazolo[4,3-a] quinazoline analogs 14-16 have superior bacterial and fungal activity when compared to the corresponding conventional doses of Streptomycin andGriseofulvin. Towards Candida albicans; compounds 14, 15, and 16 increase activity with 1.14 %, 1.15 %, and 1.21 %, respectively more than griseofulvin.While, for Staphylococcus aureus; compounds 14, 15, and 16 increase activity with 1.5 %, 1.5 %, and 1.7 %, respectively more than streptomycin. Morever, for Escherichia coli; compounds 14, 15, and 16 increase activity with 1.19 %, 1.21 %, and 1.22 %, respectively more than streptomycin. Finally, structure activity relationships show that quinazoline derivatives exhibit higher activity when fused to pyrazole ring 14-16 as compared when fused thiophene ring 7-13.

4-Halomethyl-Substituted Imidazolium Salts: A Versatile Platform for the Synthesis of Functionalized NHC Precursors.

N,N'-Diarylimidazolium salts containing haloalkyl functional groups that are reactive with various nucleophiles are considered to be promising reagents for the preparation of functionalized N-heterocyclic carbene (NHC) ligands, which are in demand in catalysis, materials science, and biomedical research. Recently, 4-chloromethyl-functionalized N,N'-diarylimidazolium salts became readily available via the condensation of N,N'-diaryl-2-methyl-1,4-diaza-1,3-butadienes with ethyl orthoformate and Me3SiCl, but these compounds were found to have insufficient reactivity in reactions with many nucleophiles. These chloromethyl salts were studied as precursors in the synthesis of bromo- and iodomethyl-functionalized imidazolium salts by halide anion exchange. The 4-ICH2-functionalized products were found to be unstable, whereas a series of novel 4-bromomethyl functionalized N,N'-diarylimidazolium salts were obtained in good yields. These bromomethyl-functionalized imidazolium salts were found to be significantly more reactive towards various N, O and S nucleophiles than the chloromethyl counterparts and enabled the preparation of previously inaccessible heteroatom-functionalized imidazolium salts, some of which were successfully used as NHC proligands in the preparation of Pd/NHC and Au/NHC complexes.

Iron (II) catalyzed cyclization of ketoxime acetates with triethyl orthoformate: An easy access to symmetrical pyridines

A simple and efficient iron (II) catalyzed approach to the synthesis of symmetrical pyridines has been demonstrated using ketoxime acetates and triethyl orthoformate in DMF at 120 °C under nitrogen environment. In this strategy, significantly, triethyl orthoformate functions as C1 carbon source and which is noteworthy. Other benefits of this process include good yields, high functional group tolerance, low cost of catalyst and avoiding of use of hazardous chemicals.

A Metal-Free Strategy for the Synthesis of Symmetrical 2,3,5,6-Tetrasubstituted Pyridines Using Triethyl Orthoformate as a Carbon Source

AbstractA simple and efficient method for the synthesis of symmetric 2,3,5,6-tetrasubstituted pyridines from enaminones and triethyl orthoformate, catalyzed by pyridinium p-toluenesulfonate, has been established in which triethyl orthoformate was applied as a carbon source. The procedure was smoothly executed, culminating in the synthesis of symmetrical 2,3,5,6-tetrasubstituted pyridines with moderate to exceptional yields across a diverse array of substrates.

Microwave-assisted Synthesis and Reactivity of Some Novel Chromenopyridine Derivatives Bearing 2,4-Diamino-3-Carbonitrile Moieties

Abstract: In the current study, we reported a cost-effective, simple strategy for the synthesis and reactivity of a novel series of chromenopyridine derivatives involving 2,4-diamino-3-carbonitrile moieties. These new compounds were synthesized in good yields from malononitrile and various chromene derivatives as a precursor, which was prepared by the reduction of iminocoumarin derivatives. The formed iminocoumarin was obtained by Knoevenagel condensation from malononitrile and different aromatic aldehydes. These novel chromenopyridine derivatives were further reacted with triethyl orthoformate under microwave irradiation to afford the final compounds, namely "chromenopyridine formimidate." The structures of all molecules were characterized by FT-IR, 1H NMR, 13C NMR, and elemental analysis.

Continuous alkylation of 1,3,5-trihydroxy-2,4,6-trinitrobenzene in microreactor: Process intensification and reaction kinetics

1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is an essential insensitive energetic material. The alkylation of 1,3,5-trihydroxy-2,4,6-trinitrobenzene (Trinitrophloroglucinol, TNPG), which yields 1,3,5-triethoxy-2,4,6-trinitrobenzene (TETNB), is a pivotal step for the synthesis of TATB. The conventional synthetic process has suffered from long reaction time (∼165 min), intricate procedures, and intensive evaporation of a large number of volatile by-products, which increases the risk of spill and eruption of the reaction system, and necessitates in situ continuous gas–liquid separation. A new process for continuous alkylation in microreactors was proposed in this study. Firstly, a parametric investigation in the batch reactor was performed to explore the effects of various process parameters on the yields, resulting in the optimal experimental conditions, i.e., no reflux condensation, triethyl orthoformate (TEOF) as alkylation reagent, molar ratio of 12, reaction temperature of 120 °C and reaction time of 40 min. Subsequent continuous synthesis in microreactors was conducted, which realized the convenient process operation and no need of gas–liquid separation, leading to substantial improvement in the reaction efficiency and safety. Remarkably, within a packed microreactor, under the reaction temperature of 130 °C and residence time of 3 min, 99.24 % in the yield of TETNB was achieved. Comparing with conventional batch reactors, the required reaction time was reduced to approximately 1/50. Taking the advantages of precise control of temperature and reaction time in the microreactors, the kinetics of alkylation reaction were determined. This innovative approach of continuous synthesis can provide an efficient and alternative route for the synthesis of TATB, as well as other energetic materials and similar processes.

A novel methodology for stabilization of silver nanoparticles on cotton, nylon and cotton/nylon fabrics using chitosan and triethyl orthoformate for enhanced and elongated antibacterial performance

In the present study, the commercially available three different fabrics cotton, nylon and cotton/nylon were modified by chitosan and silver nanoparticles using a crosslinker triethyl orthoformate (TEOF). Resulted cotton‑silver (Ag-Cs-Cot), nylon‑silver (Ag-Cs-Nyl) and cotton-nylon silver (Ag-Cs-Cot-Nyl) fabrics showed significant anti-bacterial activity even after 50 washing cycles. Silver nanoparticles were prepared by reducing silver nitrate through sodium borohydride at 0 °C. In FTIR spectra the peak at near 1650 cm−1 confirmed that TEOF mediated attachment of chitosan with fabrics (due to C=N) and the stretching of secondary amine near the 3375 cm-1 indicated the silver attachment to the amine group of the chitosan. In Scanning Electron Microscope (SEM) images smooth surfaces of fabrics without any damage by modification process were observed. The antibacterial activity was Analyzed by agar diffusion and broth dilution assays against Escherichia coli and Staphylococcus aureus bacterial strains and results showed 90% bacterial inhibition against E. coli and 89% bacterial inhibition against S. aureus. For testing the antibacterial durability, the modified fabrics were washed with non-ionic detergent (10g/l) for 15 minutes under aggressive stirring (100 rpm) at room temperature. The modified fabrics retained antibacterial activity over the 50 washing cycles. Finally, the commercial potential of cotton-silver fabric was evaluated by stitching it with the socks of football players and interestingly results showed that the modified fabric on the socks showed more than 90% bacterial inhibition as compared to the plain fabric after 70 minutes of playing activity.

Three components: one-pot synthesis of tetrazoles using silica-supported melamine tri-sulfonic acid, an efficient and reusable heterogeneous catalyst

The effective and straightforward procedure for synthesizing 1-H 1,2,3,4 tetrazole involves the reaction of a primary amine, triethyl orthoformate and sodium azide in the presence of silica-supported melamine tri sulfonic acid. One pot synthesis of tetrazole derivatives over the silica-supported melamine tri sulfonic acid catalyst reveals that the existence of strong acid sites in silica makes it more efficient with respect to the shortening of the reaction time (5–6 h) and excellent yield (75-84%) as compared to the other catalysts. This process includes benefits like a more environmentally friendly path, an easier work-up, a reusable catalyst and a high yield.

Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

AbstractHerein we report the synthesis of ten newly substituted 3‐phenyl‐5‐aryl‐3,5‐dihydro‐4H‐benzo[6,7]chromeno[2,3‐d]pyrimidin‐4,6,11‐triones (“benzochromenopyrimidines”) in a one‐step reaction, by reacting ethyl 2‐amino‐4‐aryl‐5,10‐dioxo‐5,10‐dihydro‐4H‐benzo[g]chromene‐3‐carboxylates with aniline, and triethyl orthoformate, under acidic catalyst and solvent‐free conditions. These benzochromenopyrimidines were submitted to biological evaluation for in vitro anti‐cancer activity, several derivatives showing higher activity than commonly used chemotherapeutic agents such as oxaliplatin, 5‐fluorouracil, and paclitaxel. In particular, the 5‐(2‐Methoxyphenyl)‐3‐phenyl‐3,5‐dihydro‐4H‐benzo[6,7]chromeno[2,3‐d]pyrimidine‐4,6,11‐trione was identified as the most potent inhibitor among all the new ligands, showing significant cytotoxic activity against all the cancer cell lines tested [human colon cancer cell lines, LoVo and HCT‐116; human lung cancer cells (A549 line)], as evidenced by the significant decrease in IC50 values, while maintaining low cytotoxicity against normal cells. These promising results suggest that this compound deserves further investigation as a potential hit compound for the development of a selective anticancer drug in cancer therapy.

Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies.

Some hexahydroquinoline candidates were prepared by reacting 2-amino-3-cyano-1-cyclohexylhexahydroquinoline with oxalyl chloride and triethyl orthoformate. The computational chemical approach agreed with the product-testing results. The produced substances were examined in vitro for their antiproliferative activity against liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT116) cell lines. The highest potency against the four cell lines was exhibited by hydrazide, thiosemicarbazide, and thiazolidinone derivatives. The best docking score was presented by thiosemicarbazide and thiazolidinone derivatives as they showed the highest binding to the Mcl-1 enzyme with binding energies of -8.97 and -8.90 kcal mol-1, respectively, which were higher than that of the co-crystallized ligand (LC3) with a binding energy of -8.74 kcal mol-1. Besides, the modeling pharmacokinetics disclosed their desirable drug-likeness and oral bioavailability characteristics.

Crystal structures of two formamidinium hexa-fluorido-phosphate salts, one with batch-dependent disorder.

Syntheses of the acyclic amidinium salts, morpholino-formamidinium hexa-fluorido-phosphate [OC4H8N-CH=NH2]PF6 or C5H11N2O+·PF6 -, 1, and pyrrolidinoformamidinium hexa-fluorido-phosphate [C4H8N-CH= NH2]PF6 or C5H11N2 +·PF6 -, 2, were carried out by heating either morpholine or pyrrolidine with triethyl orthoformate and ammonium hexa-fluorido-phosphate. Crystals of 1 obtained directly from the reaction mixture contain one cation and one anion in the asymmetric unit. The structure involves cations linked in chains parallel to the b axis by N-H⋯O hydrogen bonds in space group Pbca, with glide-related chains pointing in opposite directions. Crystals of 1 obtained by recrystallization from ethanol, however, showed a similar unit cell and the same basic structure, but unexpectedly, there was positional disorder [occupancy ratio 0.639 (4):0.361 (4)] in one of the cation chains, which lowered the crystal symmetry to the non-centrosymmetric space group Pca21, with two cations and anions in the asymmetric unit. In the pyrrolidino compound, 2, cations and anions are ordered and are stacked separately, with zigzag N-H⋯F hydrogen-bonding between stacks, forming ribbons parallel to (101), extended along the b-axis direction. Slight differences in the delocalized C=N distances between the two cations may reflect the inductive effect of the oxygen atom in the morpholino compound.

Understanding steric hindrance effect of solvent molecule in localized high-concentration electrolyte for lithium metal batteries

High energy density lithium metal batteries (LMBs) have garnered significant research interests in the past decades. However, the growth of lithium dendrites and the low Coulombic efficiency (CE) of Li metal anode pose significant challenges for the development of LMBs. Herein, we report a triethyl orthoformate (TEOF)-based localized high-concentration electrolyte (LHCE) that facilitates a highly reversible Li metal anode with dendrite-free deposition morphologies and an average Coulombic efficiency of 99.1% for 450 cycles. Mechanistic study reveal that the steric hindrance caused by the terminal ethyl groups in the TEOF solvent molecule results in a weak solvating ability, leading to the formation of anion-dominant solvation structures. The anion-dominant solvation sheaths play an essential role in the formation of a LiF-rich solid-electrolyte interphase (SEI), which effectively suppresses the growth of Li dendrites. Furthermore, the TEOF-based electrolyte demonstrates the stable cycling of high-voltage Li||NMC811 cells. These results provide insights into understanding of steric hindrance effect on electrolyte solvation structure and offer valuable guidance for the design of electrolyte solvents in the development of lithium metal batteries.

One-Pot Reactions of Triethyl Orthoformate with Amines

One-pot reactions offer advantages like easy automation, higher product yields, minimal waste generation, operational simplicity, and thus reduced cost, time and energy. This review presents a comprehensive overview of one-pot reactions including triethyl orthoformate and amines as valuable and efficient reagents for carrying out two-, three- or four-component organic reactions.

Design, synthesis, in-vitro biological screening and in-silico studies of 2-thioxodihydropyrimidinone based new aminomethylene scaffolds

A successful attempt was made to avail ten new 5-anilinoaminomethylene substituted 2-thioxodihydropyrimidinones (H1–H10) via one-pot three-component reaction of 1,3‑diethyl-2-thiobarbituric acid, triethyl orthoformate and respective substituted anilines in good to excellent yields (84–92 %). All the synthesized compounds were fully characterized by detailed spectroscopic techniques, like UV–Vis., IR, NMR and HRMS after purification. In-vitro investigations including DPPH free radical scavenging ability, acetyl- and butyrylcholinesterases inhibition, α-glucosidase inhibition, phytotoxicity and insecticidal activities of the synthesized compounds were performed, and very promising results were obtained. Compounds H6-H10 showed amazing potency as DPPH free radical scavengers with IC50 values of 0.88 ± 0.053, 0.54 ± 0.164, 1.22 ± 0.07, 0.20 ± 0.055 and 1.58 ± 0.123 mg/mL, respectively, better than reference compound ascorbic acid (IC50 1.79 ± 0.045 mg/mL). Similarly, compounds H2 and H4 declared greater inhibition of α-glucosidase enzyme with IC50 of 319.46 ± 1.45 and 263.57 ± 1.34 µM respectively, as compared to the reference compound acarbose (IC50 375.82 ± 1.76 µM). The bioinformatics study of the synthesized compounds comprised drug likeness, metabolites prediction, molecular docking analyses against eight selected target substrates. Docking analysis showed that the binding energy values of compounds H2, H3 and H5 were –11.25, –10.91 and –12.30 Kcal/mol respectively, which are better than standard drug diltiazem possessing –10.79 Kcal/mol against P450 CYP 3A4. Finally, the rat acute toxicities were estimated through four different routes of administration and the results reflect promising behaviors of the test compounds in their toxicity evaluation. Based on the encouraging results in all these analyses, our target compounds may be used as hits for future investigation towards drug discovery.

Pyrano-coumarin hybrids as potential antimicrobial agents against MRSA strains: Design, synthesis, ADMET, molecular docking studies, as DNA gyrase inhibitors

Due to their various pharmacological effects, several substituted nitrogen heterocycles containing coumarin have recently attracted a great deal of attention. Acetyl-coumarin was used in reactions with p-methoxy-benzaldehyde, malononitrile, and ordinary heating to produce compound 1, which contains cyano-amine, allowing for the one-pot and speedy synthesis of coumarin derivatives. Ethyl cyanoacetate, triethyl orthoformate, phenyl isothiocyanate, carbon disulfide, and benzaldehyde, were used to condense compound 1 to get the corresponding chromene derivatives 2–15. Elemental and spectroscopic evidence was used to characterize every freshly synthesized hits. S. aureus (MRSA), P. aeruginosa, E. coli, and C. albicans were the standard strains employed in this investigation. Most of the compounds displayed moderate to high activity against all the tested species, according to the early screening results with a MIC range of 0.25 to 1024 μg/mL. When compared to the positive control, compounds 3, 6, 9, and 12 showed the greatest declining reduction in the bulk of the bacterial species' biofilm. The findings of subsequent testing on the three most powerful compounds against E. coli DNA gyrase inhibitory activity revealed that all these derivatives block DNA gyrase and hence prevent cell proliferation. Additionally, successful in silico investigations for the most active compounds were conducted.

A novel formulation of triethyl orthoformate mediated durable, smart and antibacterial chitosan cross-linked cellulose fabrics

Antibacterial, durable and smart cotton fabrics was developed using chitosan-based formulation. The cellulose was covalently cross-linked with chitosan using TEOF. The antibacterial activity of prepared smart fabrics and CS was studied against S. aureus and E. coli strains. The FTIR, SEM and XRD were employed to confirm the linkage of CS molecules with cellulose in cotton fabrics. The CS of 160 KDa extracted from shrimp shell showed the optimum antibacterial activity. The prominent asymmetric, symmetric alkyl CH peaks of CS were shifted to 2930 and 2845 (cm−1), respectively. Moreover, the shifted peaks at 1590 and 1400 (cm−1) indicate the CO stretching and NH2 bending bands of CS, respectively. This confirm the existence of new imine functional group that was generated after cross-linking of NH2 groups of CS. The SEM results showed more uniform morphology of TEOF cross-linked fabrics versus CS coated fabrics, which revealed a promising microbial growth inhibition activity. The TEOF as a cross-linker has been unveiled, showcasing the effectiveness of this innovative crosslinking approach. The fabric treated with cross-linked CS exhibited remarkable antibacterial properties that endured even after undergoing 30 washing cycles. These antibacterial textiles possess substantial commercial potential across a diverse range of industries.

Improved Yields of Dichlorobis(triphenylphosphine)nickel(II) and Related Compounds by Employing Triethyl Orthoformate as an In Situ Dehydrating Agent: Rational Improvement of a Classic Undergraduate Inorganic Synthesis

Improved Yields of Dichlorobis(triphenylphosphine)nickel(II) and Related Compounds by Employing Triethyl Orthoformate as an In Situ Dehydrating Agent: Rational Improvement of a Classic Undergraduate Inorganic Synthesis

Supported gold nanoparticles on lignosulfonate coated magnetic nanoparticles: Investigation of its catalytic efficiency in the reductive formylation of nitroarenes

This article describes a biogenic synthesis towards the fabrication of Au NPs over sodium lignosulfonate (NaLS) modified Fe3O4 bio-nanocomposite and its catalytic and biological applications. The morphology and physicochemical characteristics of the material were determined over a number of analytical techniques like FT-IR, FE-SEM, TEM, EDS, XRD, ICP-OES and VSM. The prepared Fe3O4@NaLS/Au nanocomposite presented an excellent catalytic performance in the one-pot synthesis of N-formyl amines via reductive formylation of different nitrobenzene derivatives using NaBH4 as the hydride source and triethyl orthoformate [CH(OEt)3] as the formylating agent. Due to magnetic core, the nanocatalyst was retrieved magnetically with facile and recycled for 8 successive runs keeping its potential intact.

Regioselective synthesis and computational calculation studies of some new pyrazolyl‐pyridine and bipyridine derivatives

AbstractStarting from 3‐oxo‐N‐(3‐pyridyl)butanamide, as key intermediate, the title compounds were synthesized in good yields. Reaction of the pyridine‐carboxamide 1 with hydrazonoyl chlorides 3a,b and with triethyl orthoformate afforded the corresponding pyrazole‐carboxamides 6a,b, and the bis‐pyridine 7, respectively. Coupling of the pyridine‐carboxamide 1 with 3‐phenylpyrazole‐5‐diazonium chloride gave the hydrazone 10 which upon heating in pyridine afforded the pyrazolo[5,1‐c]‐1,2,4‐triazine derivative 11. Reaction of the pyridine‐carboxamide 1 with arylmethylenepropanedinitrile derivatives afforded 1,3′‐bipyridines 13a–c. Structure elucidation of the newly synthesized compounds was carried out using IR, NMR spectroscopy, and mass spectrometry. The extensive theoretical and experimental mechanical studies of the pyrazole derivative 6a were in accordance with its elemental analysis, FT‐IR, NMR, and MS spectral data. Moreover, computer analyses indicated that the pyridine derivatives 13a,b predominated over the pyran derivatives 14a,b as the adducts. In addition, the optimization of compounds utilized the HF/6‐31G(d) and DFT/B3LYP/6‐31G(d) basis sets. Furthermore, the physical descriptors of these compounds demonstrated their stability, and NMR correlation investigations were also carried out.

Evaluation of Antituberculosis Activity and in Silico Properties of Oxymethylene-cyclo-1,3-diones.

Tuberculosis is a leading infectious disease that has infected one-third of the world's population and is more prevalent among people belonging to developing countries such as India and China. In the present study, a series of substituted oxymethylene-cyclo-1,3-diones was synthesized and screened for anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv (M. tuberculosis). The compounds were synthesized by condensation of 1,3-cyclicdione, substituted phenols/ alcohols and triethyl orthoformate. The synthesized compounds were screened for anti-tuberculosis activity against M.tuberculosis H37Rv using Middlebrook 7H9 broth assay. Results demonstrated that among the synthesized library of molecules, two compounds 2-(2-hydroxyphenoxymethylene)-5,5-dimethylcyclohexane-1,3-dione and 5,5-dimethyl-2-(2-trifluoromethylphenoxymethylene)cyclohexane-1,3-dione were found to be most active against M. tuberculosis (MICs of 1.25 μg/mL-1 ). The MICs of 2-(2,4-difluoro-phenoxymethylene)-5,5-dimethylcyclohexane-1,3-dione and 2-(2-bromophenoxymethylene)-5,5-dimethylcyclohexane-1,3-dione were found to be 5 and 10 μg mL-1 , respectively. Data from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all the four most active compounds did not exhibit cytotoxicity against human cell lines. Molecular docking studies revealed that the most active compound targets mycobacterial InhA enzyme. In summary, the present study demonstrates the methodology for the synthesis of oxymethylene-cyclo-1,3-diones and identified two potential anti-tuberculosis compounds.