Secondary Aromatic Amides Research Articles

Silver-catalyzed nitrosation and nitration of aromatic amides using NOBF4.

Divergent aromatic ring nitrosation and nitration of aromatic amides are reported using NOBF4 as the electrophile under silver-catalyzed conditions. The reactions proceed efficiently with a wide range of compatible functionalities providing ortho-position nitrosation products, deacylation nitrosation products, and nitration products from different tertiary and secondary aromatic amides.

Biological Activity and Molecular Docking Study of Some Bicyclic Structures: Antidiabetic and Anticholinergic Potentials

Bicyclic structures were synthesized by LACASA-DA cycloaddition reaction using (S)-BINOL as a chiral inductor. The N-2 pyridazine position was protected; the hydroxyl group was carbonylated to form the new bicyclic structure. The protective group was removed, the double bond dehydroxylated leading to the target compound. Removing of the protective group was performed using newly found ecofriendly catalyst for N-Boc deprotection. The obtained features from the model against AChE enzyme suggest that a lower the size of the ring, number of –NH-NH- groups, number of secondary aromatic amines, number of aromatic ketone groups may contribute to the inhibitory activity. The features obtained from the model against BChE enzyme suggest that the sum of topological distances between two nitrogen atoms, number of secondary aromatic amides, may be more favorable for inhibition. The features obtained from selectivity-based model suggest that the number of aromatic ethers, unsaturation content related to their molecular size and molecular shape may be more specific for the inhibition of the AChE enzyme in comparison to the BChE enzyme. Similarly, these aromatic structures inhibited the α-glucosidase enzyme at the micromolar level due to its structural feature. Inhibition values were found to be statistically significant, especially for cholinesterase enzymes. Molecular docking method was used to compare the biological activities of molecules against enzymes. The enzymes used in this study are α-glycosidase, butyrylcholinesterase, acetylcholinesterase, respectively. ADME/T analysis was performed to use some bicyclic molecules as drugs in the future.

In silico modeling for dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes in Alzheimer’s disease

In this research, we have implemented two-dimensional quantitative structure-activity relationship (2D-QSAR) modeling using two different datasets, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzyme inhibitors. A third dataset has been derived based on their selectivity and used for the development of partial least squares (PLS) based regression models. The developed models were extensively validated using various internal and external validation parameters. The features appearing in the model against AChE enzyme suggest that a small ring size, higher number of −CH2- groups, higher number of secondary aromatic amines and higher number of aromatic ketone groups may contribute to the inhibitory activity. The features obtained from the model against BuChE enzyme suggest that the sum of topological distances between two nitrogen atoms, higher number of fragments X-C(=X)-X, higher number of secondary aromatic amides, fragment R--CR-X may be more favorable for inhibition. The features obtained from selectivity based model suggest that the number of aromatic ethers, unsaturation content relative to the molecular size and molecular shape may be more specific for the inhibition of the AChE enzyme in comparison to the BuChE enzyme. Moreover, we have implemented the molecular docking studies using the most and least active molecules from the datasets in order to identify the binding pattern between ligand and target enzyme. The obtained information is then correlated with the essential structural features associated with the 2D-QSAR models.

Enhanced reactivity of twisted amides inside a molecular cage.

When an amide group is distorted from its planar conformation, the conjugation between the nitrogen lone pair and the π* orbital of the carbonyl is disrupted and the reactivity towards nucleophiles is enhanced. Although there are several reports on the synthesis of activated twisted amides, amide activation through mechanical twisting is much less common. Here, we report twisted amides that are stabilized through their inclusion in a self-assembled coordination cage. When secondary aromatic amides are included in a Td-symmetric cage, the cis-twisted conformation is favoured over the trans-planar one-as evidenced by single-crystal X-ray diffraction analysis-revealing that the amide can twist by up to 34°. As a consequence of this distortion, the hydrolysis of amides is significantly accelerated upon inclusion.

Hydrogen Bond Directed ortho‐Selective C−H Borylation of Secondary Aromatic Amides

AbstractReported is an iridium catalyst for ortho‐selective C−H borylation of challenging secondary aromatic amide substrates, and the regioselectivity is controlled by hydrogen‐bond interactions. The BAIPy‐Ir catalyst forms three hydrogen bonds with the substrate during the crucial activation step, and allows ortho‐C−H borylation with high selectivity. The catalyst displays unprecedented ortho selectivities for a wide variety of substrates that differ in electronic and steric properties, and the catalyst tolerates various functional groups. The regioselective C−H borylation catalyst is readily accessible and converts substrates on gram scale with high selectivity and conversion.

Hydrogen Bond Directed ortho-Selective C-H Borylation of Secondary Aromatic Amides.

Reported is an iridium catalyst for ortho‐selective C−H borylation of challenging secondary aromatic amide substrates, and the regioselectivity is controlled by hydrogen‐bond interactions. The BAIPy‐Ir catalyst forms three hydrogen bonds with the substrate during the crucial activation step, and allows ortho‐C−H borylation with high selectivity. The catalyst displays unprecedented ortho selectivities for a wide variety of substrates that differ in electronic and steric properties, and the catalyst tolerates various functional groups. The regioselective C−H borylation catalyst is readily accessible and converts substrates on gram scale with high selectivity and conversion.

Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source.

Using N-methoxymethyl-N-organylcarbamoyl(trimethyl)silanes as secondary amides source, the direct transformation of aryl halides into the corresponding secondary aromatic amides via palladium-catalyzed aminocarbonylation is described. The reactions tolerated a broad range of functional groups on the aryl ring except big steric hindrance of substituent. The types and the relative position of substituents on the aryl ring impact the coupling efficiency.

External Stimulus-responsive Conformational Alterations of Aromatic Amides

Three-dimensional structure of a molecule and its alteration is an important issue, and it is essential problem for controlling the function of a molecule such as a molecular switch or device. In most cases, molecular switches have relatively high activation energy for interconversion between alternative structures, however in some biological systems, conformational preference plays an important role in regulation of bioactivity. We have interested in conformational alteration of aromatic amides, which have interesting features about conformation. Most of secondary aromatic amides such as benzanilide tend to prefer trans conformation, whereas N-methylation makes its conformation cis-favored. Recently we found several aromatic amides altered the preferred conformation depending on the external stimuli. Thus, N-phenyl-N-quinonyl type of amides changed their preferred conformation according to redox state of quinonyl moiety. N-Methyl pyridylamides showed conformational alteration according to solvent acceptor ability or addition of acid. N-Methylated pyridylamide oligomer also showed unique conformational folding and unfolding. These properties of the aromatic amides can be applied to stimuli-responsive molecular switches and functional molecules.

The alkaline hydrolysis of humic substances

A humic and a fulvic acid were subjected to four successive hydrolyses with 2 NNaOH solution at 170°C for 3 h. Following each hydrolysis, the degradation products were extracted into ethyl acetate, methylated, separated by chromatographic techniques and identified by mass spectrometry and micro-IR spectrophotometry. One g of humic acid yielded 113.5 mg of aliphatic compounds (mainly n-C 16 and n-C 15) fatty acids), 72.1 mg of phenolics (principally guaiacyl and syringyl derivative) 17.1 mg of benzenepolycarboxylic acid esters and 30.4 mg of N-containing compounds (mainly secondary aromatic amides). Repeated attacks by the alkali on 1.0 g of fulvic acid released 103.8 mg of aliphatics, 133.8 mg of phenolics, 27.0 mg of benzenecarboxylic but 181.8 mg of N-containing compounds. Most of the latter appeared to have been formed during the second, third and fourth hydrolysis which produced reactive compounds that could abstract N from diazomethane which was used as methylating reagent. While 25.0% of the initial humic acid resisted repeated attacks by the alkali, practically all of the fulvic acid was converted into ethyl acetate-soluble products. The alkali-resistant humic acid residue produced high yields of benzenepolycarboxylic acids on alkaline permanganate oxidation. Alkaline hydrolysis, which is known to cleave CO bonds, was found to be relatively specific, although not very efficient, for the degradation of structural phenolic humic and fulvic acid components and for the concomitant liberation of adsorbed aliphatics and N-containing compounds, but was relatively ineffective for degrading aromatic structures linked by CC bonds.