Formation Of Diamides Research Articles

N-Heterocyclic Carbene (NHC)-Catalyzed Tail-to-Tail Dimerization of Acrylamides

AbstractThe tail-to-tail dimerization of acrylamides enables the formation of diamides. However, only one example of N,N-dimethylacrylamide has been described in the literature. Herein, an NHC-catalyzed tail-to-tail dimerization of acrylamides in moderate to excellent yields is presented. In this context, N-arylacrylamides are susceptible to the dimerization reaction, which features high reaction efficiency, good E-selectivity, and easy operation.

Taming diamines and acyl chlorides by carbon dioxide in selective mono-acylation reactions

Selective monoacylation and unsymmetric diamide formation reactions using acyl chlorides and diamines under ambient CO2 pressure (400 ppm – 1 atm), enabling facile synthesis of bioactive molecules.

Synthesis of new Amides based on N-Phthaloyl-α-Amino Acids

N-phthaloyl derivatives of aliphatic α-amino acids were synthesized using phthalanhydride under standard conditions. The optimization reaction carried out by the thermal method to obtain the amides of these N-phthaloyl amino acids resulted in transimitted rather than amidation. The target amides of N-phthaloyl-α-amino acids were obtained by acylation of the amine with the corresponding acid chloroanhydrides in dichloromethane. These results were compared with the results of a similar acylation in a non-polar solvent (benzene). The dependence of the direction of the reaction on the duration of the acylation and the amount of amine used was established. The conditions for the formation of the corresponding N-phthaloyl-α-amino acid amides and asymmetric phthalic acid diamides were found. It is noteworthy that the formation of diamides is directly proportional to the equivalent amount of amine and the duration of the reaction, which makes it possible to purposefully control the synthesis in one reactor.

Resolving the Mystery of Ring Opening in the Synthesis of Benzo[d][1, 3]oxazin-4-one and Quinazolin-4(3H)-one

Quinazoline is the six-membered heterocyclic ring system reported for its versatile biological activities. This characteristic feature of quinazoline makes it a good template for a lead generation library. Ring opening is one of the major concerns in the synthesis of quinazolin-4(3H)-one that results in diamide formation. Here, alternative fusion strategy is reported, which is a time-saving and costeffective method to overcome the ring opening problem associated with the synthesis of benzo[ d][1,3]oxazin-4-one and quinazolin-4(3H)-one.

Protein cation exchangers derived by charge reversal from poly(ethylenimine)-Sepharose FF: Comparisons between two derivatization routes

It has been known that anion exchangers prepared by grafting poly(ethyleneimine) (PEI) onto Sepharose FF (PEI-Sepharose) at ionic capacities (IC) over 600 mmol/L show both high protein adsorption capacity and uptake kinetics, and charge reversal of PEI-Sepharose by modification with succinic anhydride can produce protein cation exchangers of high capacity and uptake rate. Previously, a Charge Reversal-then-Reduction procedure (route A) was studied for preparation of cation exchangers of different IC values from PEI-Sepharose. In this work, we proposed a new route, that is, Charge Reduction-then-Reversal route (route B), to develop cation exchangers of different IC values from PEI-Sepharose FF with an IC of 700 mmol/L (FF-PEI-L700) as the starting resin. The two kinds of cation exchangers (route A, PEI-L700-CRn; route B, PEI-Rm-Cn) are compared for lysozyme (Lys) adsorption and chromatography. The two modification routes result in the difference in the ligand structures that significantly affect protein adsorption equilibrium and kinetics. Route A introduces long electroneutral groups that hinder protein adsorption and reduce equilibrium capacity. Moreover, charge reversal by reaction with succinic anhydride could cause diamide formation, which reduces remaining carboxyl groups or the IC. In the charge-reduced FF-PEI-Rm resins of the lowest IC (394 mmol/L) prepared in route B, the diamide formation was little due to the lack of primary and secondary amine groups, so its charge reversal makes a higher-IC cation exchanger. This makes PEI-Rm-Cn show a higher IC (589 mmol/L) than PEI-L700-CRn (463 mmol/L) in which De/D0 jumps about four times. The differences in the adsorption equilibrium and kinetics make the two kinds of resins behave distinctly in dynamic adsorption and chromatography. Namely, PEI-Rm-Cn resins display obviously higher dynamic binding capacities than PEI-L700-CRn resins in the IC range studied. For instance, the DBC (at 10% breakthrough) of PEI-R590-C680 (192 mg/mL) is 33% higher than that of PEI-L700-CR680 (144 mg/mL). This is proved by the purification of Lys from chicken egg white solution, in which the PEI-R590-C680 column purified Lys with a recovery yield 14% higher than the PEI-L700-CR680 column. This research thus demonstrated that Charge Reduction-then-Reversal route is superior over Charge Reversal-then-Reduction route in fabricating a high-capacity cation exchanger from PEI-Sepharose.

Synthesis of p-aminobenzoic acid diamides based on 4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-carboxylic acid and [4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methylamine

Reaction of 4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-carboxyl chloride with anesthesin followed by hydrolysis of the formed ester has afforded 4-[4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-carbonylamino]benzoic acid. The acid chloride has been used for acylation of various amines to yield the corresponding diamides. Reaction of [4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-yl]methylamine with chlorides of N-substituted p-aminobenzoic acids has led to formation of diamides.

Synthesis of 4‐(3,4‐dicarboxamido‐1H‐pyrrole)pyrimidines as Anaplastic Lymphoma Kinase Inhibitors

To explore non‐aniline aromatic substitution on the pyrimidine C4 position, novel 4‐(N,N′‐di‐n‐propyl‐3,4‐dicarboxamido‐1H‐pyrrole)pyrimidines are designed and synthesized as anaplastic lymphoma kinase inhibitors for non‐small cell lung cancer treatment. To overcome the unexpected cleavage between the C‐N linkage of pyrrole nitrogen and C4‐pyrimidine during hydrolysis and inaccessibility of the desired diamide formation through coupling agent‐mediated conditions, the 4‐(N,N′‐di‐n‐propyl‐3,4‐dicarboxamido‐1H‐pyrrole)pyrimidine was assembled through direct nucleophilic substitution under microwave irradiation. Thus prepared 4‐(N,N′‐di‐n‐propyl‐3,4‐dicarboxamido‐1H‐pyrrole)pyrimidines were measured both ALK binding and H3122 cell proliferation assay. Their weak ALK activities are explained with molecular modeling study.

Squaric Acid Monoamide Mannosides as Ligands for the Bacterial Lectin FimH: Covalent Inhibition or Not?

Bacteria use long proteinaceous appendages, called fimbriae or pili, to adhere to the surfaces of their host cells. Widely distributed among the Enterobacteriacae are type 1 fimbriae that mediate mannose-specific bacterial adhesion through the lectin FimH, located at the fimbrial tips. It is possible to design synthetic mannosides such that they show high affinity for FimH and can thus inhibit mannose-specific bacterial adhesion in a competitive manner. It has been found that mannosidic squaric acid monoamides serve especially well as inhibitors of type 1 fimbriae-mediated bacterial adhesion, but it has remained unclear whether this effect is due to specific inhibition of the bacterial lectin FimH or to unspecific bioconjugation between the lectin's carbohydrate binding site and a squaric acid monoamide. A bioconjugation reaction would result in a covalently crosslinked squaric acid diamide. Here it is shown that covalent inhibition of FimH by mannosidic squaric acid derivatives is very unlikely and that compounds of this type serve rather as excellent specific candidates for low-molecular-weight inhibitors of bacterial adhesion. This has been verified by testing the properties of glycosidic squaric acid monoamides in diamide formation, by two different adhesion assays with a series of selected control compounds, and by molecular docking studies that further support the results obtained in the bioassays.

Isomerization in the reaction of (aminoalkyl)trialkoxysilanes with carboxylic acid anhydrides

The products of the reactions of monofunctional (3-aminopropyl)triethoxysilane and (3-aminopropyl)trimethoxysilane and bifunctional [3-N-(2-aminoethyl)aminopropyl]trimethoxysilane with acetic and maleic anhydrides in CCl4 at varied reagent molar ratios are studied by 1H and 13C NMR spectroscopy. It is shown that the reaction of [3-N-(2-aminoethyl)aminopropyl]trimethoxysilane with the above anhydrides leads to formation of diamides as mixtures of cisoid and transoid rotamers about both amide bonds. The reactions with monofunctional (aminopropyl)trialkoxysilanes give individual isomers.

Calix[4]azacrowns: self-assembly and effect of chain length and O-alkylation on their metal ion-binding properties

Both the consequences of 1,3-cyclization of calix[4]arenes by diamide formation, and the effect of 2- and 2,4-alkoxycarbonylmethylation of two 1,3-bridged calix[4]azacrowns on their metal ion-binding capacities have been studied by synthesis of the derivatives in their cone conformation and measurement of the stability constants for their complexation in a range of alkaline earth and transition metal cations. In these two cases, the conformation of the ligand in the solid state has been defined in detail by a crystal structure determination. In the first case, a tubular architecture performing methanol channels is displayed, however, in the second case a zigzag architecture generated by a chloroform network connecting calixarene molecules is present. Speciation in solution appears to be limited to the formation of 1:2 and/or 1:1 and/or 2:1 (M–L) complexes, depending on the system, with values of the stability constants determined by absorption spectroscopy in acetonitrile, lying in the ranges log β 12 ca. 10, log β 11 ca. 2–5, and log β 21 ca. 7–9. There is evidence for selectivity toward Cu(II) and for some unexpected anion effects. None of these ligands appear to be an efficient extractant for the metals as their picrate.

Solvation of Yttrium with Ammonia Revisited. Di-amide Formation in the Reaction of Yttrium with Ammonia

The reactivity of yttrium atoms toward ammonia is revisited using expanded density functional theory calculations. The new results reveal that absorption of NH3 on YNH is dissociative to form Y(NH2)2. The di-amide species can adsorb further NH3 molecules molecularly to form Y(NH2)2NH3 and Y(NH2)2(NH3)2. The calculations aimed to reveal the detail of the potential energy curves between the imide and the di-amide forms. The Y(NH2)2(NH3)x species are more stable than those of YNH(NH3)x by more than 20 kcal/mol.

Mechanisms for the Formation of Diamides and Polyamides by Aminolysis of d‐Glucaric Acid Esters

1H and 13C NMR were employed to chart the conversion of the five‐membered lactone esters methyl d‐glucarate 1,4‐lactone (1) and ethyl d‐glucarate 6,3‐lactone (5) to N,N′‐dipropyl‐d‐glucaramide with n‐propylamine in DMSO‐d6. These experiments were carried out to model the amide forming steps in polycondensation reactions between esterified d‐glucaric acid and diamines to give poly(d‐glucaramides). It was clear from the resulting NMR spectra that the lactones 1 and 5 were each converted in three consecutive steps to the product diamides; aminolysis of the lactone ester to the corresponding acyclic N‐propyl‐d‐glucaramide monoester, followed by lactonization to a five‐membered lactone amide, and concluding with aminolyis of the lactone amide to N,N′‐dipropyl‐d‐glucaramide (4). Comparison of the reaction pathways from 1 and 5 by 1H NMR analysis suggests that ring opening of the 1,4‐lactone ester (1) and 1,4‐lactone amide (7) is faster than ring opening of the corresponding 6,3‐lactone ester (5) and 6,3‐lactone amide (3). Aminolysis of dimethyl l‐tartrate, which cannot form a five‐membered lactone, with n‐propylamine in DMSO‐d6 was much slower than aminolysis of esterified glucaric acid, indicating that the lactone forming/lactone aminolysis steps are the dominant aminolysis rate enhancing steps from glucarate.

Synthesis and anti‐HIV Activity of New C2 Symmetric Derivatives Designed as HIV‐1 Protease Inhibitors.

Abstract The synthesis of several new anti-HIV-1 compounds is described. The new compounds contain a C2 symmetry axis and a dihidroxyethylene moiety based on the d -tartaric acid back bone. The synthesis of these compounds was achieved in 36–69% overall yields from d -tartaric acid. The protocol included: acetylation of hydroxyl groups, followed by diamide formation and deacetylation or reduction with LiAlH4. The anti-HIV 1 activities of these substances were evaluated in PM-1 cells, using Indinavir® as standard (IC50=0.2 μM). Two amino alcohol derivatives showed good inhibitory activity against the virus, with IC50=2.0 and 4 μM.

Synthesis and anti-HIV activity of new C2 symmetric derivatives designed as HIV-1 protease inhibitors

The synthesis of several new anti-HIV-1 compounds is described. The new compounds contain a C 2 symmetry axis and a dihidroxyethylene moiety based on the d-tartaric acid back bone. The synthesis of these compounds was achieved in 36–69% overall yields from d-tartaric acid. The protocol included: acetylation of hydroxyl groups, followed by diamide formation and deacetylation or reduction with LiAlH 4. The anti-HIV 1 activities of these substances were evaluated in PM-1 cells, using Indinavir® as standard (IC 50=0.2 μM). Two amino alcohol derivatives showed good inhibitory activity against the virus, with IC 50=2.0 and 4 μM.

Efficient synthesis of ( S, S)-ethambutol from l-methionine

Starting from readily available amino acid l-methionine, an efficient synthesis of the tuberculostatic agent ( S, S)-ethambutol has been developed. The key steps in the synthetic sequence involve: dimerization of methionine methyl ester through oxalyl diamide formation, Raney nickel desulfurization of the terminal thiomethyl groups, and a one-pot exhaustive reduction of the oxalamide and the diester functionalities to afford the desired enantiopure ( S, S)-ethambutol in good overall yield.

ChemInform Abstract: Synthesis of Polydentate Ligands Containing Amides and Thiols for Biomimetic Metal Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

SYNTHESIS OF POLYDENTATE LIGANDS CONTAINING AMIDES AND THIOLS FOR BIOMIMETIC METAL COMPLEXES

Three pentadentate “N2S3” and one tetradentate “N2S2” new ligands with “N” = CONH and “S” = SH have been synthesized. The key step is the direct diamide formation from the malonyl diester and the amines in the presence of trimethylaluminum.

Squaric Acid Diethylester: A Simple And Convenient Coupling Reagent

A new method for the covalent modification of polymers in a two-step process is described. Squaric acid diethylester reacts with primary or secondary aliphatic amines selectively to ester amides. It is shown for the first time that this class of compounds react with polymeric systems containing amine functionalities (e.g. ε-amino groups of proteins) in aqueous solution, forming stable squaric acid diamide linkages. Three different monoamides were synthesized and the reaction rates of diamide formation versus hydrolysis were determined. Detailed kinetic studies revealed that unwanted hydrolytic side-reactions are more than ten times slower than the formation of squaric acid diamides

Adhesive interface interactions between primary aliphatic amine surface conditioners and polyamic ester/polyimide resins

AbstractThe interface reactions of 3‐aminopropyltriethoxysilane treated surfaces, with a polyamic alkyl ester/polyimide resin formed from pyromellitic dianhydride and oxydianiline, were defined by Fourier Transform Infrared (FTIR) analysis on the surface layers of germanium internal reflection plates. Adhesion between these interfacial layers is the result of chemical bonding, which apparently proceeds through initial amide formation between the amino function of the silylated surface and the alkyl ester group present in the polyamic ester. Heating results in diamide formation by a second alkyl, surface‐bound amine displacing the aromatic polymer amine. Heating the more stable dialkyldiamide to 300°C imidizes both the polymer and the interfacial region, producing a strong laminate composite. Polymer scission at the aromatic amide linkages occurs in this adhesion process, bonding surface‐bound alkyl amines to one end of a shortened polymer chain.

Photochemical formation of diamides from p-nitrophenylbenzamide

Photochemical formation of diamides from p-nitrophenylbenzamide