Alkyl Amides Research Articles

Cobalt-Catalyzed Remote C-4 Functionalization of 8-Aminoquinoline Amides with Ethers via C-H Activation under Visible-Light Irradiation. Access to α-Heteroarylated Ether Derivatives.

A cobalt-catalyzed selective remote C-4 alkylation of 8-aminoquinoline amides via C-H activation under irradiation with a CFL lamp in the presence of eosin Y at room temperature has been achieved. A series of pharmaceutically important C-4 quinoline amide-substituted ether derivatives has been obtained by this procedure. The C-4 functionalization of quinoline amides with inert ether is of much significance and was not reported earlier.

Pd(ii)-Catalyzed gamma-C(sp3)–H alkynylation of amides: selective functionalization of R chains of amides R1C(O)NHR

The gamma C(sp3)-H bond alkynylation of R chains of amides R1C(O)NHR, a fundamental class of synthetic substrates, has not been accomplished to date. Here, the first example of palladium(ii)-catalyzed alkynylation of an unactivated gamma C(sp3)-H bond of alkyl amides (cyclic, linear, and amino acids) is reported. The kinetic experiment shows that the rate of the reaction depends on the coupling partners and the amides. Late-stage diversification of alkynylated amides was developed by utilizing amine and alkyne functionalities.

The Use of a Rhodium Catalyst/8-Aminoquinoline Directing Group in the C-H Alkylation of Aromatic Amides with Alkenes: Possible Generation of a Carbene Intermediate from an Alkene

Abstract Rhodium-catalyzed alkylation reactions of C-H bonds (hydroarylation) in aromatic amides that contain an 8-aminoquinoline as a directing group with alkenes are discussed. Various alkenes, including acrylic esters, styrenes, α,β-unsaturated butyrolactones, dihydrofurans, maleimides, and norbornene derivatives are applicable to this C-H alkylation. The reaction with norbornene gives unusual endo-hydroarylation products in a high degree of selectivity. The use of a carboxylic acid as an additive dramatically increases both the reactivity and the selectivity of the reaction. The results of deuterium-labeling experiments suggest that hydrometalation or carbometalation, which are commonly accepted mechanisms for C-H alkylation reactions, are not involved. Instead, the reaction appears to proceed through a rhodium carbene intermediate generated from the alkene.

Cover Feature: Synthesis and Liquid Crystalline Properties of Unsymmetrically Substituted Naphthalenediimides with a Polar Headgroup: Effect of Amide Hydrogen Bonding and Alkyl Chain Length (ChemistryOpen 1/2018)

Cover Feature: Synthesis and Liquid Crystalline Properties of Unsymmetrically Substituted Naphthalenediimides with a Polar Headgroup: Effect of Amide Hydrogen Bonding and Alkyl Chain Length (ChemistryOpen 1/2018)

Ionic Complexes of Tetra‐ and Nonanuclear Cage Copper(II) Phenylsilsesquioxanes: Synthesis and High Activity in Oxidative Catalysis

AbstractHerein, we describe an approach to cage metallasilsesquioxanes by self‐assembly with 1,2‐bis(diphenylphosphino)ethane as a key reactant. This approach allowed us to achieve a unique family of complexes that includes anionic tetra‐ and nonanuclear cage copper(II) sodium silsesquioxane and cationic copper(I) 1,2‐bis(diphenylphosphino)ethane components. Additional representatives of this intriguing metallasilsesquioxane family (Cu9Na6 and Cu9Na3Cs3) were obtained through the replacement of the original ethanol‐based reaction medium by DMSO. The fascinating structural peculiarities of all products were established by using XRD and topological studies. Initial tests for the application of the synthesized complexes as catalysts revealed their very high activity in the homogeneous oxidation of alkanes and alcohols to produce alkyl hydroperoxides, ketones, and amides.

The Potential of Alkyl Amides as Novel Biomarkers and Their Application to Paleocultural Deposits in China

A series of alkyl amides was detected and identified in the sedimentary record from an archaeological site at Yuchisi, Mengcheng, Anhui, China. The alkyl amides profiles change abruptly at the depth corresponding to the transition between two prehistoric cultures, which also corresponds to an abrupt change in the fatty acid ratio C18:2/C18:0. The different patterns of variation of the longer and shorter chain alkyl amides at the depth of the cultural transition may reflect differences in their response to external environmental changes, as well as different sources. This is the first study of the stratigraphic variation of alkyl amides in sediments, and their first application to assess paleoenvironmental changes. We suggest that alkyl amides may have potential as new biomarkers in archeological and paleoenvironmental studies.

Effect of Spacer Length between Phenyl Pendant and Backbone in Comb Copolymers on Flow Ability of Waxy Oil with Asphaltenes

Waxy crude oil containing large amounts of paraffins often results in various difficulties in extraction and transportation, especially at low temperature. Comb-type copolymers with phenyl pendants were found to be able to improve the flow ability of waxy oils effectively. To investigate the influence of spacer length between phenyl pendant and polymer backbone in comb copolymers on the flow ability of waxy oil, poly(α-octadecene-co-maleic acid phenyl alkyl amide)s with various spacer lengths were synthesized by modification of poly(α-octadecene-co-maleic anhydride) with aniline, phenethylamine, phentermine, and phenyl-undecanoicamide. Their effects on the morphology and crystallization of model and crude oils were observed by polarized light microscopy and DSC. The flow ability of both oils in the presence of copolymers was studied by means of rheology, including measuring yield stress, viscosity, and thixotropic properties. It is found that the spacer length remarkably affects the rheology and wax cryst...

Nickel-Catalyzed Reductive Transamidation of Secondary Amides with Nitroarenes

Transmidation is an attractive method for amide synthesis. However, transamidation of secondary amides is challenging. Here, we describe a reductive transamidation method that employs readily available nitro(hetero)arenes as the nitrogen sources, zinc or manganese as reductant, and simple nickel salt and ligand as a catalyst system. The scope of amides includes both alkyl and aryl secondary amides, with high functional group compatibility.

Iron Catalyzed Oxidative C(sp3)–N Cross Coupling of Amides with C(sp3)–H via a Radical Process

AbstractAn efficient iron‐catalyzed oxidative N–H alkylation of amides with C(sp3)–H in cycloalkanes, methylarenes and tert‐Butyl peroxybenzoate was developed. This protocol proceeded smoothly without any ligand; and tolerated a broad range of substrates, not only various amides but also the inactive C(sp3)−H bond containing compounds. Mechanistic details involving a Fe(II)/Fe(III) catalytic cycle and a single electron transfer (SET)‐type process were also described.

Halogen Effect on Non-Conventional Organogel Assisted by Balanced π-π Interaction

Triphenylamine-functionalized anthracene derivatives bearing no alkyl chains or amide units (ADIPA and Br-ADIPA) are synthesized in a straightforward manner. Among these two compounds, Br-ADIPA could form stable gel in organic solvents, but ADIPA cannot gelate any conventional solvents under the tested conditions. In order to disclose the supramolecular self-assembly of Br-ADIPA gel, a series of characterizations were performed, which indicated that it might self-assemble into aggregates which do not involve π-π stacking between anthracene chromophore in the gel state, and intermolecular π-π interactions between phenyl rings on triphenylamine moieties are essential driven forces for its gelation. Interestingly, the self-assemblies of these two compounds calculated using Polymorph software well matched the characterization results. It revealed that a one-dimensional molecular packing was promoted by multiple intermolecular π-π interactions between triphenylamine units in Br-ADIPA, and the bromine atom played important role in its balanced intermolecular π-π interactions. In comparison, these supramolecular forces in ADIPA provided a three-dimensional structure.

Alkylsilyl Peroxides as Alkylating Agents in the Copper-Catalyzed Selective Mono-N-Alkylation of Primary Amides and Arylamines.

The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides.

Metal–free C5‐H Bromination of Quinolines for One‐pot C−X (X=C, O, S) Bond Formations

AbstractWe developed an efficient and convenient method for metal‐free bromination of 8‐aminoquinoline scaffolds on the C5 position that is geometrically inaccessible. And this bromination step can be followed in a one‐pot manner with five kinds of C−X (X=C, O, S) cross‐coupling reactions without any extra workup, such as removal of the solvent or filtration for the separation of intermediate. The reaction tolerates a wide scope of alkyl and aryl amides as well as (hetero)aryl boronic acids, generating the corresponding arylation products in good to excellent yields. Furthermore, the one‐pot alkenylation, alkynylation, thiolation and phenoxylation of quinolines on the C5 position can be efficiently realized using this brominated quinoline amide molecular platform. Thus, the method shows high practical potential in industrial organic synthesis.magnified image

Safety Assessment of Amino Acid Alkyl Amides as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the product use, formulation, and safety data of 115 amino acid alkyl amides, which function as skin and hair conditioning agents and as surfactants-cleansing agents in personal care products. Safety test data on dermal irritation and sensitization for the ingredients with the highest use concentrations, lauroyl lysine and sodium lauroyl glutamate, were reviewed and determined to adequately support the safe use of the ingredients in this report. The Panel concluded that amino acid alkyl amides are safe in the present practices of use and concentration in cosmetics, when formulated to be nonirritating.

Ruthenium(II)‐Catalyzed C−C Arylations and Alkylations: Decarbamoylative C−C Functionalizations

AbstractRuthenium(II)biscarboxylate catalysis enabled selective C−C functionalizations by means of decarbamoylative C−C arylations. The versatility of the ruthenium(II) catalysis was reflected by widely applicable C−C arylations and C−C alkylations of aryl amides, as well as acids with modifiable pyrazoles, through facile organometallic C−C activation.

Ruthenium(II)-Catalyzed C-C Arylations and Alkylations: Decarbamoylative C-C Functionalizations.

Ruthenium(II)biscarboxylate catalysis enabled selective C-C functionalizations by means of decarbamoylative C-C arylations. The versatility of the ruthenium(II) catalysis was reflected by widely applicable C-C arylations and C-C alkylations of aryl amides, as well as acids with modifiable pyrazoles, through facile organometallic C-C activation.

Practical and General Manganese‐Catalyzed Carbonylative Coupling of Alkyl Iodides with Amides

AbstractA selective manganese‐catalyzed carbonylative transformation of alkyl iodides and amides was developed. A variety of imides were prepared in moderate to good yields. Alkyl bromides could also be applied by in situ treatment with NaI to give the corresponding alkyl iodides. Notably, no additives or expensive ligands were required here. As the first example of the carbonylative coupling of alkyl iodides with amides, the simple reaction conditions and the advantages of a manganese catalyst make this new general procedure more attractive and practical than conventional techniques. Mechanistically, control experiments and electron paramagnetic resonance spectroscopy studies were also performed, and the radical nature of this new process was proven.

Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis

A series of novel alkyl amide functionalized 2,3-pyrazole fused quinoline derivatives 5, 6 and 7 have been prepared starting from quinoline-2(1H)one 1 in a series of steps. All the final products were screened for antibacterial activity, the promising lead compound 5r was identified with MIC values ranging between 3.9 and 7.8 μg/mL against different bacterial strains. Compound 5r also showed good antifungal and anti-biofilm activities against the tested panel of various fungal and bacterial strains. Compound 5r when treated on mature biofilms of S. aureus strain MLS16, showed increased levels of intracellular ROS accumulation suggesting its contribution to the bactericidal activity. All the compounds were also screened for anticancer activity against a panel of four human cancer cell lines. Based on these studies, compounds 5c, 5d, 5r and 7f were considered as promising and exhibited significant cytotoxicity with IC50 values of <15 μM. The biological activity data was further validated by molecular modeling and CoMFA studies.

Studies on Cycloalkane-Based Bisamide Organogelators: A New Example of Stochastic Chiral Symmetry-Breaking Induced by Sonication.

Enantiomerically pure C16 -alkyl amides derived from cis and trans cycloalkane-1,2-dicarboxylic acids, respectively, have been synthesized and their behavior as organogelators has been investigated. These compounds include cis/trans diastereomeric cyclobutane and cyclohexane derivatives with the aim to explore the influence of the ring size as well as the relative configuration in their hierarchical self-assembly to form gels. High resolution 1 H NMR spectroscopy studies allowed the determination of the dynamics of the gelation process in [D8 ]toluene and the sol-gel transition temperature. The morphology and size of the aggregates have been investigated and results have shown that, in the case of cyclobutane derivatives, the cis/trans stereochemistry is not relevant for the gelation behavior and the properties of the soft-materials obtained, but it is remarkable for cyclohexane diamides, which are better organogelators. The four compounds produce chiral aggregates despite that two of them are meso achiral molecules. We show herein that this fact is an example of stochastic symmetry breaking induced by sonication. The self-assembly of these molecules has been modelled providing information and support about the structure and the chirality of the aggregates.

Preparation of "Constrained Geometry" Titanium Complexes of [1,2]Azasilinane Framework for Ethylene/1-Octene Copolymerization.

The Me2Si-bridged ansa-Cp/amido half-metallocene, [Me2Si(η5-Me4C5)(NtBu)]TiCl2, termed a “constrained-geometry catalyst (CGC)”, is a representative homogeneous Ziegler catalyst. CGC derivatives with the [1,2]azasilinane framework, in which the amide alkyl substituent is joined by the Si-bridge, were prepared, and the catalytic performances of these species was studied. Me4C5HSi(Me)(CH2CH=CH2)-NH(C(R)(R’)CH=CH2) (R, R’ = H or methyl; Me4C5H = tetramethylcyclopentadienyl) was susceptible to ring closure metathesis (RCM) when treated with Schrock’s Mo-catalyst to afford -Si(Me4C5H)(Me)CH2CH=CHC(R)(R’)NH- containing a six-membered ring framework. Using the precursors and the products of RCM, various CGC derivatives, i.e., [-Si(η5-Me4C5)(Me)CH2CH=CHC(R)(H)N-]TiMe2 (13, R = H; 15, R = Me), [-Si(η5-Me4C5)(Me)CH2CH2CH2CH2N]TiMe2 (14), [(η5-Me4C5)Si(Me)(CH2CH=CH2)NCH2CH=CH2]TiMe2 (16), [(η5-Me4C5)Si (Me)(CH=CH2)NCH2CH=CH2]TiMe2 (17), and [(η5-Me4C5)Si(Me)(CH2CH3)NCH2CH2CH3]TiMe2 (18), were prepared. The catalytic activity of the newly prepared complexes was lower than that of CGC when activated with [Ph3C][B(C6F5)4]/iBu3Al. However, the catalytic activity of these species was improved by using tetrabutylaluminoxane ([iBu2Al]2O) instead of iBu3Al and the activity of 14/[Ph3C][B(C6F5)4]/[iBu2Al]2O was comparable to that of CGC/[Ph3C][B(C6F5)4]/iBu3Al (4.7 and 5.0 × 106 g/mol-Ti, respectively). Advantageously, the newly prepared complexes produced higher molecular weight poly(ethylene-co-1-octene)s than CGC.

Zinc-catalyzed chemoselective alkylation of α-keto amides with 2-alkylazaarenes.

A zinc-catalyzed C(sp3)-H addition of 2-alkylazaarenes to α-keto amides to furnish azaarene incorporated α-hydroxy amides has been developed with a wide range of substrates in moderate to excellent yields, respectively. Chemoselective alkylation of the keto functionality of the α-keto amides in the presence of simple ketones is the key advantage of this Zn-catalyzed transformation. This approach has been demonstrated to one gram-scale synthesis. 1H NMR and D2O exchange experimental studies reveal that the reaction proceeds through a Zn-enamide intermediate.