Synthesis of bicyclic 2,6-diketopiperazines via a three-step sequence involving an Ugi five-center,four-component reaction

A three-step sequence involving an Ugi five-center, four-component reaction (U-5C-4CR), amide N-detertbutylation and cyclocondensation has been developed for easy access to diverse bicyclic 2,6-diketopiperazine (2,6-DKP) derivatives. In the key step, aromatic aldehydes were successfully coupled with cyclic α-amino acids and isocyanides in the course of U-5C-4CR. Boron trifluoride-acetic acid complex was developed as a new N-detertbutylating agent effective at rt.     

A simple synthesis of ferrocenyl bis-amides by a Ugi four-component reaction

An efficient and simple synthesis of ferrocenyl bis-amides by the Ugi four-component reaction of ferrocenecarboxaldehyde, carboxylic acids, isocyanides and amines in methanol at room temperature is reported.     

Direct synthesis of the arylboronic acid analogues of phenylglycine via microwave-assisted four-component Ugi reaction

A four-component Ugi reaction (Ugi-4CR) utilizing formylphenyl boronic acids under mild condition was developed for the synthesis of arylboronic acid analogs. The reactions were performed in methanol and accelerated by microwave irradiation, which makes this strategy suitable for constructing boronic-containing chemical libraries. Two of the synthesized analogs were found to have cytotoxic activity against HepG2, MDA-MB231, and A549 cancer cell lines, demonstrating the potential application of this approach in developing novel boron-containing pharmaceuticals.     

Trimesic acid is a suitable building block in triple four-component Ugi reaction: access to unique trivalent compounds

Monatshefte für Chemie - Chemical Monthly - A triple four-component Ugi reaction of isocyanide, amine, aldehyde, and trimesic acid as the acid component with three acidic functional groups in...     

Synthesis of tetrazolodiazepines by a five-centered four-component azide Ugi reaction. Scope and limitations

Tetrazolo[1,5-a][1,4]benzodiazepines were obtained by an efficient azide five-centered four-component Ugi reaction, which used ketones, sodium azide, ammonium chloride, and the corresponding isonitrile. Scope and limitations of this multi-component reaction were considered.     

Rapid access to oxindoles by the combined use of an Ugi four-component reaction and a microwave-assisted intramolecular Buchwald-Hartwig amidation reaction

A two-step sequence involving an Ugi four-component reaction (Ugi-4CR) and a palladium-catalyzed intramolecular amidation of aryl iodide has been developed for rapid access to functionalized oxindole (1). Microwave heating was used to accelerate and to improve the efficiency of the intramolecular Buchwald-Hartwig reaction.     

Synthesis of spirooxindoles promoted by the deep eutectic solvent,ZnCl2+urea via the pseudo four-component reaction: anticancer,antioxidant, and molecular docking studies

Abstract

Various spirooxindoles (7a–c, 8a–c, 9a–c, and 10a–c) were efficiently synthesized using deep eutectic solvent ZnCl₂+urea and well characterized using IR, ¹H NMR, and ¹³C NMR spectroscopic techniques. The biological screening results showed that the compound 9a exhibited potent anticancer activity against MCF7 and HeLa cell lines with IC₅₀ values 6.47?±?0.01 and 9.14?±?0.32?µM, respectively. The compound 7c exhibited potent activity against the HeLa cell line with IC₅₀ value 6.81?±?0.01?µM. The compound 9a exhibited a potent antioxidant activity with IC₅₀ value 7.34?±?0.17?µM. The comparative molecular docking study against the cancer proteins EGFR and HER2 revealed that the EGFR was the best target protein receptor for the target compounds. Among all the compounds, the compound 9a exhibited the least binding energy ?10.72?kcal/mol against the protein EGFR (PDB ID: 4HJO).     

Diastereoselective synthesis of gamma-lactams by a one-pot, four-component reaction

A new one-pot, four-component reaction (4CR) between amines, maleic anhydrides, aldehydes, and thiols has been discovered to form tetra- and pentasubstituted gamma-lactams with high diastereoselectivity. Each component is independently variable and employed in equivalent stoichiometry, producing only water as a byproduct.     

Bioactive 2-oxazolines: a new approach via one-pot, four-component reaction

Substituted 2-oxazolines of the general structure shown above are found in several families of bioactive natural products and can be prepared in an efficient and general one-pot, four-component condensation.     

Ugi four-component condensation with two cleavable components: the easiest synthesis of 2,N-diarylglycines

The Ugi four-component condensation between anilines, aromatic aldehydes, isocyanides, and α-oxoacids afforded the expected adducts which were cleaved in mild conditions to give 2,N-diarylglycines in high yields.     

The role of solvent in sonochemical reactions: the case of acetic acid

Among the sonolysis products of acetic acid, oxidizing intermediates can play a direct role in reactions run in this solvent, illustrating the fact that organic sonochemistry can originate in organic solvents as aqueous sonochemistry can in water.     

Zirconium-mediated intramolecular ester transfer reaction: synthesis of alpha-substituted gamma-aminobutyric acid (GABA) derivatives

[reaction: see text]. The zirconium-mediated intramolecular ester transfer reaction of N-alkenyl carbamate derivatives proceeded to give alpha-substituted gamma-aminobutyric acid (GABA) derivatives in good to excellent yields. Quenching experiments of the reaction mixture with iodine or O2 indicated the presence of a cyclopropane intermediate. The resulting iodide was converted to 2-substituted pyrrolidine-3-carboxylate and/or alpha-alkylidene-gamma-aminobutyric acid derivatives in a stereospecific manner.     

Microwave-assisted four-component reaction for the synthesis of a monothiohydantoin inhibitor of a fatty acid amide hydrolase

Monothiohydantoin 3a is made in seven steps from 1,4-diiodobenzene and is shown to be an inhibitor of fatty acid amide hydrolase (IC₅₀ = 23.4 ± 1.1 μM). The key step in the sequence involves a microwave-assisted four-component reaction that makes the 5,5′-disubstituted hydantoin nucleus by the sequential formation of two C-C and two C-N bonds.     

An efficient, “green” approach to aryl amination of cyanuric chloride using acetic acid as solvent

Acetic acid is an inexpensive and environmentally friendly solvent for facile, clean and high‐yielding aryl amination of cyanuric chloride with aromatic amines, including nitroanilines. Aryl amination in acetic acid medium and isolation protocol are greatly simplified as compared to previously reported procedures. Under proper conditions, it is possible to attach the same or different aniline residues in a controlled way to obtain in excellent yields symmetrical and unsymmetrical 1,3,5‐triazine derivatives, respectively.     

The effect of solvent on a Lewis acid catalyzed Diels-Alder reaction,using computed and experimental kinetic isotope effects

A new transition structure for the Diels-Alder reaction between isoprene and acrolein catalyzed by Et(2)AlCl is found to reconcile reported discrepancies between computed and observed secondary kinetic isotope effects (KIEs). Including the effect of solvent realigns the computed results with experiment demonstrating the importance of nonbond interactions at transition structures. Comparison of experimental and newly predicted KIE data reaffirms the ability of theory and experiment to probe the mechanism and transition structure geometry of organic reactions.     

Determination of chloride and sulfate in semiconductor-grade etchants comprised of acetic acid,nitric acid and phosphoric acid

The variable-capacity Dionex Cryptand A1 column was used for the determination of low-ppm levels of chloride and sulfate in etchants comprised of acetic acid, nitric acid and phosphoric acid. All possible ratios of the three acids could be analyzed for chloride and sulfate, if the samples were first diluted 1:100. However, a suitable eluent program was found to be needed for each mixture. A proprietary formulation was chosen to undergo this suitability determination. The resulting gradient was 10 mM KOH with a step to 30 mM NaOH at 15 min, flow-rate=0.5 ml/min; column temperature=29 degrees C; sample loop=7.5 microl. Under these conditions, a low-ppm calibration study (using the proprietary mix as the matrix) was performed and the associated prediction intervals were determined. At 50 ppm (in the original etchant), the +/- prediction interval was +/- 7 ppm for chloride and +/- 20 ppm for sulfate, both at the 95% confidence level. This step gradient was found to be a good starting place for separating the five components in all other ratios of these three acids.     

Zinc chloride catalyzed three-component Ugi reaction: synthesis of N-cyclohexyl-2-(2-hydroxyphenylamino)acetamide derivatives

The ability of zinc chloride as a catalyst to promote the three-component Ugi reaction of 2-aminophenols, aliphatic or aromatic aldehydes, and cyclohexyl isocyanide in methanol at room temperature is described. The N-cyclohexyl-2-(2-hydroxyphenylamino) amide products are obtained in high yields. When N,N-dimethylformamide dimethyl acetal and triethyl orthoformate, as two new components of the three-component Ugi reaction are used instead of the aldehyde the reaction gives N-cyclohexyl-2-(dimethylamino)-2-(2-hydroxyphenylamino)acetamide and N-cyclohexyl-2-(2-hydroxyphenylamino)-2-ethoxyacetamide derivatives, respectively.     

Ions with a strong symmetric H-bond in solutions of sodium acetate in acetic acid

The multiple attenuated total reflection IR spectra of solutions of sodium acetate in acetic acid have been recorded in the range from 9000 to 4000 cm^–1. The CH₃COO^– anion and an acid molecule form be complex (CH₃COO...H...OOCCH₃) with a strong symmetric H-bond.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp, 1854–1857, July, 1996.     

Copper-catalyzed cross-coupling of imines, acid chlorides, and organostannanes: a multicomponent synthesis of alpha-substituted amides

A copper-catalyzed cross-coupling of organotin reagents with imines and acid chlorides is reported. The reaction proceeds efficiently with a range of vinyl-, alkyl-, aryl- and heteroaryl-substituted organostannanes as well as a diverse set of imines of non-enolizable aldehydes. Use of chloroformates also allows for the formation of N-protected alpha-substituted amines. This chemistry has been applied to the synthesis of isoquinoline alkaloid derivatives through the activation of cyclic imines.