Ortho-substituted Groups Research Articles

Design, synthesis, and in vitro evaluation of novel antifungal triazoles containing substituted 1,2,3-triazole-methoxyl side chains

In order to develop new triazole derivatives, we optimized the lead compound a6 by structural modifications to obtain a series of (2R,3R)-3-((1-substituted-1H-1,2,3-triazol-4-yl) methoxy)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol, compounds 5–36. Most of the target compounds exhibited excellent in vitro antifungal activity against Candida albicans 10231 and Candida glabrata 537 with MIC ≤ 0.125 µg/mL. Of particular note, compounds 6, 22, 28, 30 and 36 were highly active against Candida neoformans 32609 with MIC ≤ 0.125 µg/mL and showed broad-spectrum antifungal activity including against fluconazole-resistant Candida auris 891. In addition, compounds 6 and 22 demonstrated inhibitory effects on filamentation in the azole-resistant C. albicans isolate. Moreover, compounds 6 and 22 were minimally toxic to HUVECs and possessed weak inhibitory effects on the human CYP3A4 and CYP2D6. SARs and docking study further indicated that ortho-substituted groups in the terminal phenyl ring can promote the compounds to improve their antifungal activity.

Ortho-substitution groups promoted photo-induced E (trans) → Z (cis) isomerization

The past decades have witnessed the fast growth of ortho-directing group assisted in CH activation and olefination. Herein we addressed these olefination products’ photo-induced E → Z isomerization in term of various ortho-substitution groups. Initially, we discovered ortho benzoxazolyl aryl acrylates effectively undertook E → Z isomerization (up to 88% yields) under 365 nm direct irradiation. Furthermore, scoping other five directing groups in CH activation and olefination revealed that acetylamino group also present to be good ortho-substituted groups that enhancing E → Z isomerization. Controlled experiment shows the substitution position is vital for photo-induced isomerization or [2 + 2] cycloaddition. Lastly, prevalent interesting fluorescent quenching/change phenomenon were always in accompany with the isomerization. X-ray single crystallography disclose the isomerization process undertook significant conjugated distortion of the aryl acrylates fragment, we proposed such change could contribute to fluorescent and absorbent decrease.

Photoresponsive Behavior of Wormlike Micelles Constructed by Gemini Surfactant 12-3-12·2Br- and Different Cinnamate Derivatives.

The photoresponsive wormlike micelles constructed by Gemini surfactants and cinnamate derivatives play a great role in the field of smart materials. However, how the structure of cinnamate derivatives affects the photoresponsive behavior of micelles is still a hotspot for scientists to research. Here, three kinds of aromatic salts with different ortho-substituted groups including trans- o-methoxy cinnamate ( trans-OMCA), trans- o-hydroxy cinnamate ( trans-OHCA), and trans-cinnamate ( trans-CA) were introduced into Gemini surfactant 12-3-12·2Br- aqueous solutions to construct photoresponsive wormlike micelles through their noncovalent interactions. Their properties were researched using the rheological method, cryo-transmission electron microscopy, and 1H NMR and two-dimensional nuclear Overhauser effect spectra. The results show that these cinnamate derivatives could well construct wormlike micelles with 12-3-12·2Br-. Furthermore, subtle differences in the ortho substituents' structure have a significant effect on the photoresponsive behavior of formed wormlike micelles. Specifically, the zero viscosity (η0) of 40 mM 12-3-12·2Br-/24 mM trans-OHCA mixed solution decreases from 26.72 to 2.6 Pa·s with the shortening of the length of wormlike micelles after UV irradiation. Correspondingly, the η0 for the same ratio of 12-3-12·2Br-/ trans-OMCA decreases from 2.42 to 0.06 Pa·s and the wormlike micelles are transited into rodlike micelles and even spherical micelles after the same UV irradiation time. However, the variation of wormlike micelles in the 12-3-12·2Br-/ trans-CA system induced by UV light is not obvious with η0 being maintained at around 2.89 Pa·s. This study will help us better understand the effects of chemical groups on macrophenomena and microinteraction for micellar systems. It provides a theoretical basis for the construction of photoresponsive micelles, thus widening their application in the field of soft materials.

Effect ofortho-substituted aniline on the corrosion protection of aluminum in 2 mol/L H2SO4solution

Corrosion protection of aluminum in 2 mol/L H2SO4solution is examined in the presence of ortho-substituted aniline derivatives using potentiodynamic polarization and electrochemical impedance spectroscopy measurements. Density function theory (DFT) calculations are performed to investigate the aluminum–electrolyte interface relationship in the absence and presence of both ortho-substituted aniline derivatives and sulphate anions, as well as their roles in the protection efficiency at the atomic level. Our results show that ortho-aniline derivatives are good inhibitors and that their efficiencies improved as the concentration increased. SEM–EDX analysis is used to confirm the adsorption thermodynamics of the studied compounds on the aluminum surface. The best inhibitory effect is exhibits in the presence of the methyl group in ortho-position followed by ortho-carboxilic compared to aniline. The adsorption of these compounds on the aluminum surface is well described by Langmuir adsorption isotherm as well as the experimental and the theoretical adosrption energies are in a good agreement. DFT calculations also show that the interaction between the inhibitors and the aluminum surface is mainly electrostatic and depends on the type of the ortho-substituted group in addition to the sulphate anions.

ChemInform Abstract: A Convenient Synthesis of N‐Aryl Benzamides by Rhodium‐Catalyzed ortho‐Amidation and Decarboxylation of Benzoic Acids.

The rhodium-catalyzed amidation of substituted benzoic acids with isocyanates by directed CH functionalization followed by decarboxylation to afford the corresponding N-aryl benzamides is demonstrated, in which the carboxylate serves as a unique, removable directing group. Notably, less common meta-substituted N-aryl benzamides are generated readily from more accessible para- or ortho-substituted groups by employing this strategy.

A convenient synthesis of N-aryl benzamides by rhodium-catalyzed ortho-amidation and decarboxylation of benzoic acids.

The rhodium-catalyzed amidation of substituted benzoic acids with isocyanates by directed CH functionalization followed by decarboxylation to afford the corresponding N-aryl benzamides is demonstrated, in which the carboxylate serves as a unique, removable directing group. Notably, less common meta-substituted N-aryl benzamides are generated readily from more accessible para- or ortho-substituted groups by employing this strategy.

Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones

In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and synthesized which contained different substituents at ortho-position of 2-phenyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the synthesized compounds exhibited a varying degree of inhibitory activity towards thymidine phosphorylase (TP), comparable to reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value=42.63μM). The study also inferred that the ortho-substituted group at the phenyl ring and 5-thio-alkyl moiety imparted steric hindrance effects in the binding site of the enzyme, leadingto areducedinhibitory response. In addition, compound 3a was identified as a mixed-type inhibitor of TP. Moreover, computational docking study was performed to illustrate the important structural information on the plausible ligand-enzyme binding interactions.

Predictors of Polychlorinated Biphenyl Concentrations in Adipose Tissue in a General Danish Population

Polychlorinated biphenyls (PCBs) are ubiquitously present in the environment and suspected of carcinogenic, neurological, and immunological effects. Our purpose was to identify predictors of adipose tissue levels of mono-, di-, and tri-ortho-substituted PCBs experienced by a general population and to establish whether predictors vary according to substitution group. In this study of 245 randomly selected persons from a prospective Danish cohort of 57,053 persons, we examined geographical area, age, lactation, BMI, and intake of eight major dietary groups as potential determinants of adipose concentrations of mono-, di-, and tri-ortho-substituted PCBs by linear regression analyses. Lactation, BMI, and intake of fruit, vegetables, and dairy products showed negative associations with PCB concentrations in adipose tissue in all models, and living in Copenhagen city, age, and consumption of fish (particularly fatty fish) were positively associated. The associations between several of the predictors and mono-ortho-substituted PCBs tended to differ from the associations found for di- and tri-ortho-substituted PCBs. In conclusion, geography, age, lactation, BMI, and consumption of fatty fish consistently predicted the concentration of PCBs in adipose tissue. Our results indicate that predictors of PCBs varied according to substitution group, suggesting that ortho-substituted groups should be analyzed separately.

Intermediate and Mechanism of Hydroxylation of o-Iodophenol by Salicylate Hydroxylase1

Salicylate hydroxylase [EC 1.14.13.1] from Pseudomonas putida catalyzes the hydroxylation of salicylate, and also o-aminophenol, o-nitrophenol, and o-halogenophenols, to catechol. The reactions with these o-substituted phenols comprise oxygenative deamination, denitration, and dehalogenation, respectively. The reaction stoichiometry, as to NADH oxidized, oxygen consumed, and catechol formed, is 2 : 1 : 1, respectively. The mechanisms for the deiodination and oxygenation of o-iodophenol were investigated in detail by the use of I(+)-trapping reagents such as DL-methionine, 2-chlorodimedone, and L-tyrosine. The addition of the traps did not change the molar ratio of catechol formed to NADH oxidized, nor iodinated traps produced were in the incubation mixture. The results suggest that I+ was not produced on the deiodination in the hydroxylation of o-iodophenol. On the other hand, L-ascorbate, L-epinephrine, and phenylhydrazine increased the molar ratio. o-Phenylenediamine decreased it, being converted to phenazine. This suggests that o-benzoquinone is formed in the oxidation of o-iodophenol as a nascent product. The quinone was detected spectrophotometrically by means of the stopped-flow method. Kinetic analysis of the reactions revealed that o-benzoquinone is reduced nonenzymatically to catechol by a second molecule of NADH. A mechanism of elimination for the ortho-substituted groups of substrate phenols by the enzyme is proposed and discussed.

Hydroxylation of o-Halogenophenol and o-Nitrophenol by Salicylate Hydroxylase1

Salicylate hydroxylase [EC 1.14.13.1] from Pseudomonas putida catalyzed the formation of catechol from substrate analogues such as o-nitro-, o-amino-, o-iodo-, o-bromo-, and o-chloro-phenol by removing the ortho-substituted groups. They are converted into nitrite, ammonia, and halide ions, respectively. Kinetic parameters of these reactions were determined by spectrophotometric and polarographic methods. Hydroxylation of o-nitro- or o-iodophenol proceeds with the unusual stoichiometry of 2:1:1 for consumed NADH, O2-uptake, and catechol formed. Other ortho-substituted phenols examined also gave the same results. Like salicylate, these substrates perturb the absorption spectrum of salicylate hydroxylase in the visible region, indicating the formation of enzyme.substrate complexes. Titration experiments with ortho-substituted phenols gave the dissociation constants of the complexes. The complexes were quantitatively reduced with NADH or dithionite without detectable formation of the intermediates. The fact that one atom of 18O2 was incorporated into the produced catechol in hydroxylation of o-nitrophenol indicates that the reaction is of monooxygenase nature. It is concluded that salicylate hydroxylase cleaves the C-N and C-X bonds of ortho-substituted phenols.

Spectrometric Studies on the Complexation of Zr(IV) with Azopyrazolonic Derivatives

Abstract Spectrometric studies on the complexation of Zr(IV) with five new pyrazolonic derivatives were carried out. The influence of ortho-substituted groups on the operational parameters of the spectrometric method of determining Zr(IV) was investigated. The absorption spectra revealed that the wavelengths of the absorption maxima of the azopyrazolonic derivatives are different from those of the zirconium compounds. Beer-Lambert

Studies of Organic Catalytic Reactions. VI. The Function of Pyridine and Copper in the Rosenmund-von Braun Reaction

Abstract The Rosenmund-von Braun reaction with aryl halide, with its Ar-X+CuCN-Base→Ar-CN+CuX-Base, has been studied in nitrobenzene in place of an organic base at 160–180°C. The free nitriles formed during the reaction were determined exactly by gas chromatography. In the use of bases with suitable coordination forces to CuCN, the reactivity of the base for the substitution was found to be in the order: prim.>sec.>tert. A steric hindrance of the base was observed, and the reactivity of the pyridine homologue followed the order: pyridine>quinoline>α-picoline>2, 6-lutidine. Ortho-substituted groups in the halobenzene seem to manifest no steric hindrance on the reaction. From the results of the kinetic study, it can be said that CuCN participates in the reaction essentially in the form of a Base(1 mol)-CuCN complex. The overall reaction is second-order, dc⁄dt=k[Complex][Ar-X]. The rate-determining step may be in the halogen exchange stage in the intervening complex, Base-CuCN-Ar-X, where the plane including CN-Cu-X and that of the benzene ring may be nearly perpendicular to each other. When an excess of CuCN over the base is used, the base is liberated from the Base-CuX complex, after the displacement, and then coordinates to the unreacted CuCN again.