N-substituted Benzamides Research Articles

Spectroscopic and theoretical investigation of solvent effect on N–H∙∙∙O, N–H∙∙∙N and N–H∙∙∙π interactions in complexes of N-monosubstituted benzamides

In this research, experimental and theoretical spectral analysis of N-monosubstituted benzamides was performed by mid-infrared spectroscopy and density functional theory. The MIR spectroscopic characteristics for N–H∙∙∙O, N–H∙∙∙N and N–H∙∙∙π hydrogen-bonded complexes and also the equilibrium constants for 1:1 complex formation are given. The structures of selected N-substituted benzamides (as proton donors), benzene, acetonitrile, and tetrahydrofuran (as proton acceptors), as well as their complexes, were optimised at the M06-2X/6–311++G(d,p) level of theory. The solvent effect on hydrogen-bonded complexes and the correlations between the equilibrium constants and molecular descriptors of N-monosubstituted benzamides were also investigated using a principal component analysis.

Reductive cross-coupling of N-acyl pyrazole and nitroarene using tetrahydroxydiboron: synthesis of secondary amides.

We report on a new method for the synthesis of amides using acyl pyrazoles and nitroarenes under reducing conditions. It was found that acyl pyrazoles react with organo-nitro compounds in the presence of B2(OH)4, giving the corresponding amides in good yields. We demonstrated that benzoyl pyrazoles having various substituents and nitroarenes with different substituents can be used to produce a range of N-substituted benzamides. The method shows good functional group tolerance and has potential application in the synthesis of a variety of organic molecules.

Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents.

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.

Copper(I)-catalysed aerobic oxidative selective cleavage of C[sbnd]C bond with DMAP: Facile access to N-substituted benzamides

A base/DMAP system for efficient oxidative cleavage of C(CO)–C(alkyl) bond to generate N-substituted benzamides has been developed in the presence of copper(I) chloride. The usage of inexpensive copper catalyst, broad substrate scope, mild conditions make this protocol very practical. More importantly, this reaction provides an alternative approach for the construction of useful N-substituted benzamides.

Synthesis and Single Crystal Structures of N-Substituted Benzamides and Their Chemoselective Selenation/Reduction Derivatives.

A series of N-aryl-N-(2-oxo-2-arylethyl) benzamides and cinnamides has been prepared. The reaction of the benzamides with Woollins’ reagent, a highly efficient chemoselective selenation/reduction reagent, gave the corresponding N-aryl-N-(arylenethyl) benzoselenoamides in good yields. Five representative single crystal X-ray structures are discussed.

Synthesis and biological evaluation of novel N-substituted benzamides as anti-migration agents for treatment of osteosarcoma

A novel series of novel N-substituted (indole or indazole) benzamides were synthesized, and their anti-tumor properties were evaluated. The majority of tested compounds possessed moderate cytotoxicity, but inspiringly, we verified that active compound 5d presents an astonishing advantage by inhibiting the adhesion, migration, and invasion of osteosarcoma (OS) cells invitro. Mechanistically, we confirmed 5d inhibited the migration ability of OS cells via the expression of genes related to adhesion, migration, and invasion. This effects of 5d suggest that it can be used as a potential chemotherapeutic drug to some aggressive and/or metastatic cancers, as well as in combination with other clinical anti-cancer drugs. In turn, this could enhance the therapeutic effect or reduce the risk of cell migration.

Copper-catalyzed amidation of benzoic acids using tetraalkylthiuram disulfides as amine sources

ABSTRACTA facile method for the copper-catalyzed synthesis of N-substituted benzamides was explored. In the presence of CuBr and di-tert-butyl peroxide, various N-substituted benzamides were prepared through amidation of benzoic acid by using commercially available and cheap tetraalkylthiuram disulfides as amine sources. With this protocol, a series of 14 N-substituted benzamides were furnished in good to excellent yields. The broad substrate scope and good to excellent yield show its practical synthetic value in organic synthesis.

Synthesis of isoindolinones via a ruthenium-catalyzed cyclization of N-substituted benzamides with allylic alcohols

N-Substituted aromatic and heteroaromatic amides reacted with substituted allylic alcohols in the presence of a ruthenium catalyst, AgSbF6 and a Cu(OAc)2·H2O oxidant, affording 3-substituted isoindolinone derivatives with diverse substituents in good to excellent yields. A possible reaction mechanism involving a five-membered ruthenacycle intermediate was proposed and strongly supported by experimental evidence.

ChemInform Abstract: Aminocarbonylation of (Hetero)aryl Bromides with Ammonia and Amines Using a Palladium/DalPhos Catalyst System.

AbstractAmmonia acts as both nucleophile and base in these reactions.

Inorganic base-catalyzed formation of antivirally active N-substituted benzamides from α-amido sulfones and N-nucleophile

BackgroundHeteronucleophiles as well as carbanionic reagents can be used to react with α-amido sulfones, thus giving the opportunity to prepare a large array of amino derivatives. Since, novel 1,3,4-oxadiazole-2-thiol derivatives can serve as potent nucleophiles, we employed 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the nucleophilic source of nitrogen in the reaction with α-amido sulfones.ResultsA series of N-substituted benzamides bearing 1,3,4-oxadiazol unit were prepared for the first time by the reaction of in situ generated protected imine from α-amido sulfones with 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the source of nitrogen nucleophile. Some of the synthesized products displayed favourable antiviral activity against cucumber mosaic virus (CMV) in preliminary antiviral activity tests. The title compounds 5c, 5o and 5r revealed curative activity of 42.2%, 48.7% and 40.5%, respectively against CMV (inhibitory rate) compared to the commercial standard Ningnanmycin (53.4%) at 500 μg/mL.ConclusionA practical synthetic route to N-benzoyl-α-amido sulfones by the reaction of 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the source of nitrogen nucleophiles with in situ generated protected imine from N-benzoyl-α-amido sulfones is presented. The reaction catalyzed by an inorganic base has considerable significance to exploit the potential of α-amido sulfones in organic synthesis.

The preparation and antifungal activity of some salicylic acid derivatives.

Abstract A series of 2-alkoxy derivatives of benzamide, halogenated benzamides, 3-naphthamide, and N-substituted benzamides has been prepared and tested in vitro as potential antifungal agents. 2-n-Amyloxybenzamide, the most active of the derivatives studied, is a slow-acting fungicide of greater fungistatic potency than undecylenic acid, N-n-butyl-3-phenyl-salicylamide, salicylanilide, Nystatin, phenylmercuric acetate, sodium ethylmercurithiosalicylate and 8-hydroxyquinoline.

Annulation of Benzamides with [60]Fullerene through Palladium(II)-Catalyzed C−H Bond Activation

Palladium-catalyzed heteroannulation of N-substituted benzamides with [60]fullerene, which proceeds through direct sp(2) C-H bond activation to form 7-membered ring pallada-intermediate with C(60), led to formation of [60]fulleroisoquinolinones in moderate to good yields (8-64% based on recovered C(60)). A plausible reaction pathway is proposed.

Formation of biogenic amines in fillets and minced flesh of three freshwater fish species stored at 3 °C and 15 °C

The aim of the present study was to compare the dynamics of biogenic amines formation in three freshwater fish species, to compare the progress of chemical changes in filleted and minced flesh, to find correlations of such changes with sensory properties and to find possible quality indicators for selected fish species. Samples (n = 156) of fish fillets and fish mince of common carp (Cyprinus carpio), rainbow trout (Oncorhynchus mykiss) and perch (Perca fluviatilis) were stored at 3 °C and 15 °C. The amines were determined as the N-substituted benzamides, after derivatization with benzoylchloride by micellar electrokinetic capillary chromatography. Based on the biogenic amine contents and sensory properties, the shelf life of samples at 3 °C was 11–16 days and 7–10 days for fillets and mince, respectively, and 2–3 days at 15 °C regardless of sample processing. Content of putrescine seems to be a good quality indicator for all examined fish species. The fish species and the method of flesh processing did not have a significant influence on the putrescine formation. Tyramine was formed mainly in carp and trout mince at 15 °C. Samples of good and acceptable quality did not contain toxicologically significant concentrations of histamine or tyramine. Contrary to marine fish, information about biogenic amines contents in freshwater fish is scarce. Comparison of the dynamics of amines formation in fillets and processed fish flesh has not been studied yet. The progress of decomposition processes is compared based on dynamic models.

Palladium mediated synthesis of isoindolinones and isoquinolinones

The palladium-catalyzed reactions of 2-iodo- N-substituted benzamides 5– 10 with acrylic esters 11– 14 led to N-substituted-3-alkylisoindolinone esters 15– 22 in good yields. The esters of isoindolinones 15– 22 underwent hydrolysis reactions yielding the N-aryl-1,2,3,4-tetrahydro-1-oxoisoquinoline-3-carboxylic acid 26– 31 in good yields.

Acylation of Aromatic Compounds with Isocyanates Catalyzed by Ytterbium(III) Triflate: Environmentally Friendly.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regioselective Synthesis of 1,4,6-Trisubstituted-2-Pyridinones and 2,3-Disubstituted (2H)-Isoquinolin-1-ones via Tandem Stille Reaction/Heterocyclisation

A general route to 1,4,6-trisubstituted 2-pyridinones and 2,3-disubstituted (2H)-isoquinolin-1-ones from (Z)-3-iodovinylic amides 1a-h and 2-iodo N-substituted benzamides 2a-f is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-β-iodovinylic amides 1a-h and 2-iodobenzamides 2a-f with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine and tetrabutylammonium bromide in acetonitrile provided good yields of the corresponding 1,4,6-trisubstituted 2-pyridinones 3a-k and 2,3-disubstituted (2H)-isoquinolin-1-ones 4a-i via tandem Stille reaction and 6-endo-dig azacyclisation.

Synthesis and potent antimicrobial activity of some novel 4-(5, 6-dichloro-1H-benzimidazol-2-yl)-N-substituted benzamides.

A series of 4-(5, 6-dichloro-1H-benzimidazol-2-yl)-N-substituted benzamides were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), methicillin-resistant S. epidermis (MRSE), Enterococcus faecalis, Escherichia coli and Candida albicans. Certain compounds inhibit bacterial growth with low MIC values (microg/mL). Among them, compounds 10 and 11 exhibited the greatest antibacterial activity with MIC values of 3.12 microg/mL against S. aureus, MRSA and MRSE.

Acylation of aromatic compounds with isocyanates catalyzed by ytterbium(III) triflate : environmentally friendly

Aromatic compounds can be acylated by isocyanates in the presence of catalytic amount of ytterbium(III) triflate [Yb(OTf) 3 ] to obtain the corresponding N-substituted benzamides in good yields under neutral conditions. The catalyst can easily be recovered and reused without any loss of activity.

One‐Pot Synthesis of 2,4‐Benzodiazepin‐1‐ones Using Benzotriazole Methodology.

2, 4-Benzodiazepin-1-ones were prepared in moderate to good yields by reaction of bis(benzotriazolylmethyl)amines with ortho-metalated N-substituted benzamides.

Differential usage of I [formula omitted]B [formula omitted] and I [formula omitted]B [formula omitted] in regulation of apoptosis versus gene expression

In this study we use the N-substituted benzamides declopramide (3-CPA) and N-acetyl declopramide (Na-3-CPA) to investigate the involvement of the transcription factor NF-κB in the induction of apoptosis and surface immunoglobulin κ (Igκ) expression in the mouse pre-B cell line 70Z/3. We first showed that 3-CPA-induced apoptosis at doses around 500 μM and that the 3-CPA-induced apoptosis could be suppressed by over-expression of the Bcl-2 protein. Na-3-CPA was shown to be non-apoptotic at doses up to 1–2 mM. On the other hand, Na-3-CPA inhibited LPS-induced Igκ expression while 3-CPA had no effect. Further analysis showed that while 3-CPA inhibited breakdown of IκBα, Na-3-CPA inhibited breakdown of IκBβ. In addition, we used a 70Z/3 cell line expressing a dominant negative IκBα (70Z/3 ΔNIκBα). The 70Z/3 ΔNIκBα cell line was shown to be more sensitive to apoptosis and cytotoxicity induced by 3-CPA as well as by LPS, probably due to a defect in NF-κB rescue mechanism. Taken together, our data implicate distinct roles for IκBα and IκBβ in regulating various NF-κB activities.