Retracted: Palladium‐Catalyzed Decarboxylative Selective Acylation of 4H‐Benzo[d][1,3]oxazin‐4‐one Derivatives with α‐Oxo Carboxylic acids via Preferential Cyclic Imine‐N‐Directed Aryl C−H Activation

The benzoxazine scaffolds are of much interest as they are found in a large array of natural products and pharmaceutical drugs with diverse activities. We have developed a palladium‐catalyzed decarboxylative selective mono‐ and bis‐acylation of 4H‐benzo[d][1,3]oxazin‐4‐one derivatives with α‐oxo carboxylic acids via preferential cyclic imine‐N‐directed C−H activation. 2‐Aryl‐4H‐benzo[d][1,3]oxazin‐4‐one was acylated with a variety of substituted phenylglyoxylic acids to produce the corresponding products. It was observed that electron‐donating groups (CH₃, OCH₃) at any position of the aromatic ring of phenylglyoxylic acid provided good to excellent yields, whereas phenylglyoxylic acids containing electron‐withdrawing groups (COCH₃, CN, NO₂) gave the products in moderate yields. Interestingly when the reaction was performed with silver triflate (AgOTf) in place of silver nitrate (AgNO₃) in the presence of 4 equivalents of glyoxylic acid, the bis‐acylated product was obtained together with a small amount of mono‐acylated product. This is the first report of acylation of 2‐aryl‐4H‐benzo[d][1,3]oxazin‐4‐ones via C−H activation. The notable features of this reaction are acylation with more challenging heteroarene‐oxo carboxylic acids and alkyl oxo carboxylic acids. This new protocol provides an easy and efficient access to a variety of o‐acyl‐4H‐benzo[d][1,3]oxazin‐4‐one derivatives which are of pharmaceutical importance.

     

Facile synthesis of some novel 4-{3-aryl-3, 4-dihydro-2H-benzo[b][1,4] thiazin-2-yl}-2H-chromen-2-one derivatives

A protocol for chemoselective one pot synthesis of 4-{3-aryl-3, 4-dihydro-2H-benzo[b][1,4]thiazin-2-yl}-2H-chromen-2-ones 4 and 4-{3-aryl-3, 4-dihydro-2H-benzo[b][1,4]thiazin-2-yl}-2H-chromen-2-ones 6 under refluxing conditions has been developed. Starting from 4-bromomethylcoumarin and Schiff base, which is derived from o-aminothiophenol and substituted aromatic aldehydes, the intermediate sulfide spontaneously underwent intramolecular carbanion addition across the azomethine carbon.     

A general synthesis of pyridazino[4,3- e ][1,3,4]thiadiazines

A straightforward synthesis of pyridazino[4,3-e][1,3,4] thiadiazines 3(a–j) from cyclocondensation of 3,6-dichloro-4-(1-methylhydrazino) pyridazine (2) with various isothiocyanates is described.     

Synthesis and Antimicrobial Activity Evaluation of Imidazole-Fused Imidazo[2,1-b][1,3,4]thiadiazole Analogues

Three series of new imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues (compounds 20 a – g , 21 a – g , and 22 a – g ) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram-positive and -negative bacteria. N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline ( 21 a ) showed the highest activity against C. albicans (MIC₅₀=0.16 μg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast-1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents.     

Mannich bases and novel benzothiazole derivatives of imidazo[2,1-b][1,3,4]thiadiazoles and their biological evaluation

A series of 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles, their new Mannich bases and novel benzothiazole derivatives were synthesized. The structures of all the synthesized compounds were established by analytical and spectral data. All the compounds were screened for their antitubercular activity against Mycobacterium tuberculosis H₃₇Rv using the BACTEC 460 radiometric system and antibacterial activity against E. coli and B. cirrhosis, antifungal activity against A. niger and P. worthmanni. Among the tested compounds Mannich bases 3e, 3f and 4 g and 5-carbaldehyde derivative 6d have shown excellent inhibition (99, 99, 97 and 95%, respectively) against M. tuberculosis. Mannich bases in general have also shown impressive antifungal activity.     

An efficient synthesis of [1,3,4]thiadiazolo[2,3-c][1,2,4] triazin-4-ones

A three-component reaction between 4-amino-6-methyl-3-thioxo-3,4-dihydro-2H-[1,2,4]triazin-5-one, ammonium thiocyanate and aroyl chlorides in the presence of N-methylimidazole to afford the [1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones in excellent yields is described.     

Synthesis of Fluorinated Imidazole[4,5f][1,10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage

Phenanthroline derivatives containing fluorinated imidazole ring are effective anti-neoplastic agents. Herein, a series of four fluorinated imidazole[4,5f][1,10]phenanthroline derivatives were synthesized and investigated as potential inhibitors to fight against the growth of liver cancer cells. The in vitro antitumor activity of targeted compounds have been evaluated by using MTT assay, and results showed that compound 4 (2-(2,3-difluorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) exhibited excellent inhibitory effect against the growth of various tumor cells, particularly for HepG2 cells, with IC₅₀ value of approximately 0.29 μM. This result has been further confirmed by colony formation assay, showing that compound 4 suppressed the proliferation of HepG2 cells. Moreover, cell apoptosis (AO/PI dual staining and flow cytometry) analyses as well as comet assay showed that compound 4 may induce apoptosis of HepG2 cells through triggering DNA damage. Furthermore, the in vivo anti-tumor activity were evaluated on zebrafish bearing HepG2 cells showed that compound 4 can observably block the growth of liver cancer cells. All in together, these compounds, particularly compound 4 , may be developed as a potential agent to treat liver cancer in the future.     

Catalytic application of N,2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide on the synthesis of 1-carbamato-alkyl-2-naphthols and 1-thioamido-alkyl-2-naphthols

A novel N-bromo sulfonamide reagent, namely N, 2-dibromo-6-chloro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide, is prepared and employed as a new and highly efficient catalyst for the preparation of 1-carbamato-alkyl-2-naphthol and 1-thioamido-alkyl-2-naphthol derivatives.     

Synthesis and anti-bacterial activity of novel dihydrochromeno[8,7-e][1,3]oxazine-2(8H)-thiones

A novel series of sulfur-containing dihydrochromeno[8,7-e][1,3]oxazine-2(8H)-thiones has been synthesized through an eco-friendly Mannich-type condensation cyclization reaction of 7-hydroxy-4-methyl-2-thiocoumarin or 6-chloro-7-hydroxy-4-methyl-2-thiocoumarin with formaldehyde and primary amines in water at 80–90°C for 2 h. All the synthesized compounds were screened for their in vitro anti-bacterial efficacy against two Gram-positive and three Gram-negative bacterial strains by using the disc diffusion method. The compound (8c) was found to be most potent with the zone of inhibition of 16 and 15 mm against Staphylococcus aureus ATCC 2937 and Klebsiella pneumoniae ATCC 31488, respectively.     

Efficient Synthesis of Benzothiazinone Analogues with Activity against Intracellular Mycobacterium tuberculosis

8-Nitrobenzothiazinones (BTZs) are a promising class of antimycobacterial agents currently under investigation in clinical trials. Starting from thiourea derivatives, a new synthetic pathway to BTZs was established. It allows the formation of the thiazinone ring system in one synthetic step and is applicable for preparation of a wide variety of BTZ analogues. The synthetic procedure furthermore facilitates the replacement of the sulphur atom in the thiazinone ring system by oxygen or nitrogen to afford the analogous benzoxazinone and quinazolinone systems. 36 BTZ analogues were prepared and tested in luminescence-based assays for in vitro activity against Mycobacterium tuberculosis (Mtb) using the microdilution broth method and a high-throughput macrophage infection assay.     

Design,Synthesis, and Biological Evaluation of Novel 6H-Benzo[c]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors

Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC₅₀: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.     

Negative effect of [bmim][PF6] on the catalytic activity of alcohol dehydrogenase: mechanism and prevention

BACKGROUND: [bmim][PF₆] is a hydrophobic ionic liquid which could be considered as an environmentally friendly solvent for biocatalysis. In pure [bmim][PF₆], however, alcohol dehydrogenase from yeast (YADH) has no catalytic activity. The aim of the present work was (1) to quantitatively study the negative effect of [bmim][PF₆] on the catalytic activity of YADH and the related mechanism and (2) to made an attempt to lessen the negative effect of [bmim][PF₆] on YADH by microemulsifying [bmim][PF₆]. RESULTS: The activity of YADH in the homogeneous solution formed by H₂O, CH₃CH₂OH and [bmim][PF₆] decreased rapidly with the increase of the molar fraction of [bmim][PF₆]. The inhibitory effect of [bmim][PF₆] on YADH was probably caused by the competition of the imidazole group of [bmim][PF₆] with the coenzyme NAD⁺ for the binding sites on YADH. In a water‐in‐[bmim][PF₆] microemulsion, YADH was catalytically active due to the formation of the interfacial membrane of the nonionic surfactant TritonX‐100, which separated YADH from [bmim][PF₆] and avoided the direct inactivation of [bmim][PF₆] on YADH. Under optimal conditions, the activity of YADH was as high as 51 µmol L^?1 min^?1. CONCLUSION: [bmim][PF₆] was an inhibitor of YADH and its negative effect on YADH could be lessened by its microemulsification. Copyright © 2008 Society of Chemical Industry     

An Efficient Synthesis of Fused Polycyclic Triazolo[4,5-a]acridine Derivatives under Catalyst-Free Conditions with High Regioselectivity

An efficient synthesis of fused polycyclic 11-aryl-7,8,9,11-tetrahydro-1H-[1,2,3] triazolo[4,5-a]acridin-10(6H)-one derivatives is described in EtOH with high regioselectivity. This new procedure includes a three-component reaction of benzaldehyde, 1H-benzo[d] [1,2,3]triazol-5-amine and cyclohexane-1,3-dione under catalyst-free conditions, and has the advantages of one-pot reaction, milder reaction conditions, high yields and high regioselectivity.     

Solvent-Free One-Pot Synthesis of 1,8-Dioxo-Decahydroacridines by a [Et3NH][HSO4] Catalyzed Multicomponent Reaction

ABSTRACT

[Et₃NH][HSO₄] has been used as an effective catalyst for one-pot, three-component condensation of an aromatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione and ammonium acetate for the synthesis of 1,8-dioxo-decahydroacridines under solvent-free conditions. The present methodology offers several advantages, such as high yields, short reaction times, mild condition, and a recyclable catalyst with a very easy work-up.     

Synthesis and in vivo Evaluation of Fluorine‐18 and Iodine‐123 Pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A2A Receptors

Imaging agents that target adenosine type 2A (A_2A) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson′s disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A_2A receptor density and function in neurodegenerative diseases. We previously described the successful evaluation of two A_2A‐specific radiotracers in both nonhuman primates and in subsequent human clinical trials: [¹²³I]MNI‐420 and [¹⁸F]MNI‐444. Herein we describe the development of both of these radiotracers by selection from a series of A_2A ligands, based on the pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A_2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine‐18 or iodine‐123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7‐(2‐(4‐(4‐(2‐[¹⁸F]fluoroethoxy)phenyl)piperazin‐1‐yl)ethyl)‐2‐(furan‐2‐yl)‐7H‐pyrazolo[4,3‐e][1,2,4]triazolo[1,5‐c]pyrimidin‐5‐amine ([¹⁸F]MNI‐444) and 7‐(2‐(4‐(2‐fluoro‐4‐[¹²³I]iodophenyl)piperazin‐1‐yl)ethyl)‐2‐(furan‐2‐yl)‐7H‐imidazo[1,2‐c]pyrazolo[4,3‐e]pyrimidin‐5‐amine ([¹²³I]MNI‐420) as PET and SPECT radiopharmaceuticals for mapping A_2A receptors in brain.     

High-quality freestanding flexible poly(5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1H-indole) film: Electrosyntheses,characterization, and optical properties

The electron-donating substituted indole is generally difficult to be polymerized into high-quality film. The electrochemical polymerization of the electron-donating 3,4-ethylenedioxythiophene (EDOT)-monosubstituted indole may be a challenge. Herein, we designed and synthesized a novel fluorescent comonomer based on the combination of indole and EDOT groups, namely, 5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1H-indole (EDTI), and subsequently electrodeposited into flawless freestanding flexible poly(5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1H-indole) (PEDTI) film with a resistance of 60 MΩ/cm in CH₂Cl₂ containing 0.1 M Bu₄NBF₄. Electrochemical results showed that the oxidation onset potential of EDTI was at 0.8 V vs Ag/AgCl, which was lower than those of indole (0.96 V vs Ag/AgCl) and EDOT (1.35 V vs Ag/AgCl). FTIR spectra indicated that the polymerization of EDTI occurred at the 5-position on thiophene ring and 2,3-positions on indole ring, forming the crosslinking polymer film. The colors of as-prepared PEDTI could switch reversibly from purple to brown under applied potentials of 1.3 and −1.3 V, which were distinctly different from those of polyindole, poly(3,4-ethylenedioxythiophene) (PEDOT), and poly(EDOT-bis-substituted indole) (PETI). Fluorescence spectral studies revealed that the comonomer and corresponding polymer were good blue-green light emitters. These results implied that PEDTI had potential applications for photoelectric devices such as electrochromic devices, light-emitting diodes, and fluorescence sensors. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47016.     

Optimization of [Bmim][HSO4]-Catalyzed Transesterification of Camelina Oil

1-Butyl-3-methylimidazolium hydrogen sulfate ([Bmim][HSO₄]) is utilized to catalyze transesterification of camelina oil with methanol. The major compositions of camelina biodiesel are saturated fatty acid esters (C16:0, C18:0), monounsaturated, and polyunsaturated fatty acid esters (C18:2, C18:3). The effects of reaction temperature, reaction time, M_methanol:M_{Camelina oil}, and M_[Bmim][HSO4]:M_{Camelina oil} on biodiesel production are investigated in detail, and a general mathematical model is developed to well predict the biodiesel yield. Also, [Bmim][HSO₄] is thermally stable to recycle for four times with a high biodiesel yield. The fuel properties of camelina biodiesel are all comparable to the American Society for Testing Materials (ASTM) standards.     

A macrocyclic ligand 5,14-dihydro-6,15-dimethyl-8,17-diphenyldibenzo-[b,i][1,4,8,11]tetraazacyclotetradecine and its nickel(II) complex: Syntheses, reaction mechanism and structures

The template reaction of o-phenylenediamine, 1-benzoylacetone and nickelous acetate tetrahydrate results in two structure isomers, 6,17-dimethyl-8,15-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecinatonickel (II) (2) and 6,15-dimethyl-8,17-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecinatonickel (II) (4). However, the latter has been neglected in the previous research because of its low yield in the template reaction. The mechanism of this template reaction is discussed. Though the steric hindrance between the phenyl ring and the benzo ring in 2 is greater than that in 4, the intermediate of the former shows better structural stability than that of the latter, leading to obviously higher final yield of 2 compared with that of 4. n-Butyl alcohol is used artfully to separate the crude product of the template reaction into almost pure 2 and a mixture of 2 and 4 in a mole ratio of 1:5. The free base of 2, 5,14-dihydro-6,17-dimethyl-8,15-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine (1), can be synthesized by demetalization of 2 with gaseous HCl. The same treatment to the mixture of 2 and 4 in a mole ratio of 1:5 leads to the free base of 4, 5,14-dihydro-6,15-dimethyl-8,17-diphenyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine (3). The neglected macrocyclic compounds 3 and 4 have been characterized unambiguously and their single-crystal structures have also been determined by X-ray diffraction analysis for the first time.     

A new route for the synthesis of pyrimido[2,1-b][1,3]thiazine ring system

A simple and efficient pathway to conjugate monosaccharides to thienopyrimidines via click chemistry establishing a 1,2,3-triazole linker was reported. Potential pharmaceutical interest is envisaged for the expected target products. Starting from a 2-isothiocyanate-thiophene-3-carboxylate, an allylthiourea was obtained with allylamine, cyclized and S-propargylated to give a thienopyrimidine–alkyne core. Click reaction with tetraacetyl-1-azidoglucose was successful to give the target conjugate with one sugar unit. When propargylamine was used in the first step, the expected thiourea cyclized via the alkyne moiety leading to pyrimido[2,1-b][1,3]thiazine.     

Enhanced catalytic performance of H2SO4-catalyzed C4 alkylation by formyl functional [N1,1,1,1][C10SO4] additive

It is of fundamental importance to assess the additive for isobutane alkylation catalyzed by the concentrated H₂SO₄ in actual industrial reactor, which usually contains 6.0–7.0 wt% red oil (ASO) impurity. Herein, the formyl functional [N_1,1,1,1][C₁₀SO₄] additive was developed to enhance the catalytic performance of the H₂SO₄ taken from industrial stream with emphasis on process optimization and reaction kinetics. The ASO that existed in the H₂SO₄ from industrial stream has a promoting effect, and the introduction of [N_1,1,1,1][C₁₀SO₄] with ratio of 0.3 wt% can further improve research octane number of alkylate even in a shorter reaction time. The kinetic model can well predict the concentration changes of key components, in which [N_1,1,1,1][C₁₀SO₄] contributes to the larger reaction rate and lower activation energy for the targeted trimethylpentanes generation due to the intensified isobutane solvation. Hopefully, the novel additive has a promising application to optimize the H₂SO₄-catalyzed industrial alkylation process.