17194-90-0

Upstream product

• 103-82-2 phenylacetic acid 
• 2627-86-3 (S)-1-phenyl-ethylamine 
• 60-12-8 2-phenylethanol 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 
• 426225-26-5 ((R)-1-Phenyl-ethyl)-[1-pyridin-4-yl-meth-(E)-ylidene]-amine 
• 201230-82-2 carbon monoxide 
• 100-39-0 benzyl bromide 
• 1158473-78-9 C₁₆H₁₄N₂S 
• 929045-26-1 C₁₃H₁₄N₂S 
• 3129-98-4 (R)-benzylidene-(1-phenylethyl)amine 
• 125875-26-5 N-(2-pyridylmethylene)-(R)-1-phenylethylamine 
• 103-81-1 Benzeneacetamide 
• 103-80-0 phenylacetyl chloride 
• 536-74-3 phenylacetylene 

Downstream Products

• 103-82-2 phenylacetic acid 
• 3886-69-9 (R)-1-phenyl-ethyl-amine 

Relevant academic research and scientific papers

Ni-Catalyzed Regiodivergent and Stereoselective Hydroalkylation of Acyclic Branched Dienes with Unstabilized C(sp3) Nucleophiles

Two complementary regiodivergent [(P,N)Ni]-catalyzed hydroalkylations of branched dienes are reported. When amides are employed as unstabilized C(sp3) nucleophiles, a highly regioselective 1,4-addition process is favored. The addition products are obtained in high yield and with excellent stereocontrol of the internal olefin. With use of a chiral ligand and imides as carbon nucleophiles, a 3,4-addition protocol was developed, enabling construction of two contiguous tertiary stereocenters in a single step with moderate to high levels of diastereocontrol and excellent enantiocontrol. Both methods operate under mild reaction conditions, display a broad scope, and show excellent functional group tolerance. The synthetic potential of the 3,4-hydroalkylation reaction was established via a series of postcatalytic modifications.

An Efficient Palladium-Catalysed Aminocarbonylation of Benzyl Chlorides

An improved procedure for the aminocarbonylation of benzyl chloride derivatives using carbon monoxide and either primary or secondary amines has been developed. Studying the competing background alkylation reaction allowed the solvent and base to be selected for a simple catalyst screen, which, in turn, enabled the discovery of a method for the preparation of 2-arylacetamides under mild conditions, with minimal side-products using an inexpensive phosphine ligand. This non-traditional optimisation strategy allowed us to overcome the background alkylation, which has been cited as justification for the development of more complex and less atom-economical approaches.

Ruthenium-Catalyzed Oxidative Amidation of Alkynes to Amides

Complex CpRuCl(PPh3)2 catalyzes reactions of terminal alkynes with 4-picoline N-oxide and primary and secondary amines to afford the corresponding amides. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry. Stoichiometric studies reveal that the true catalysts of the processes are the vinylidene cations [CpRu(=C=CHR)(PPh3)2]+ which are oxidized to the Ru(η2-CO)-ketenes by the N-oxide. Finally, nucleophilic additions of primary and secondary amines to the free ketenes yield the corresponding amides.

CuH-Catalyzed Asymmetric Hydroamidation of Vinylarenes

A CuH-catalyzed enantioselective hydroamidation reaction of vinylarenes has been developed using readily accessible 1,4,2-dioxazol-5-ones as electrophilic amidating reagents. This method provides a straightforward and efficient approach to synthesize chiral amides in good yields with high levels of enantiopurity under mild conditions. Moreover, this transformation tolerates substrates bearing a broad range of functional groups.

Air-stable Bis(pentamethylcyclopentadienyl) Zirconium Perfluorooctanesulfonate as an Efficient and Recyclable Catalyst for the Synthesis of N-substituted Amides

Bis(pentamethylcyclopentadienyl) zirconium perfluorooctanesulfonate is an air-stable and water-tolerant Lewis acid. This complex exhibited good thermal stability and high solubility in polar organic solvents. The compound showed relatively strong acidity, with an acid strength of 0.8Ho≤3.3, and high catalytic efficiency for the synthesis of N-substituted amides via the reaction of carboxylic acids with amines, the Ritter reaction of nitriles with alcohols, and the amination of alcohols with amides. Moreover, the complex had good reusability. This catalytic system affords a simple and efficient way to synthesize N-substituted amides.

Mechanistic Elucidation of Zirconium-Catalyzed Direct Amidation

The mechanism of the zirconium-catalyzed condensation of carboxylic acids and amines for direct formation of amides was studied using kinetics, NMR spectroscopy, and DFT calculations. The reaction is found to be first order with respect to the catalyst and has a positive rate dependence on amine concentration. A negative rate dependence on carboxylic acid concentration is observed along with S-shaped kinetic profiles under certain conditions, which is consistent with the formation of reversible off-cycle species. Kinetic experiments using reaction progress kinetic analysis protocols demonstrate that inhibition of the catalyst by the amide product can be avoided using a high amine concentration. These insights led to the design of a reaction protocol with improved yields and a decrease in catalyst loading. NMR spectroscopy provides important details of the nature of the zirconium catalyst and serves as the starting point for a theoretical study of the catalytic cycle using DFT calculations. These studies indicate that a dinuclear zirconium species can catalyze the reaction with feasible energy barriers. The amine is proposed to perform a nucleophilic attack at a terminal η2-carboxylate ligand of the zirconium catalyst, followed by a C-O bond cleavage step, with an intermediate proton transfer from nitrogen to oxygen facilitated by an additional equivalent of amine. In addition, the DFT calculations reproduce experimentally observed effects on reaction rate, induced by electronically different substituents on the carboxylic acid.

A one-pot amidation of primary nitroalkanes

It has been over a half-century since Kornblum demonstrated the conversion of a primary nitroalkane to a carboxylic acid; addition of an amine results in carboxylic acid formation as well. We describe the formation of amides from terminal nitroalkanes in a two-step, one-pot reaction involving tandem halogenation/umpolung amide synthesis (UmAS).

Hafnium-catalyzed direct amide formation at room temperature

Herein, the first example of a metal-catalyzed protocol for direct amidation of nonactivated carboxylic acids at ambient temperature (26 °C) is presented. The mild reaction conditions give rise to high yields of a range of amides in reaction times as short as 90 min, employing a commercial hafnium complex, [Hf(Cp)2Cl2], as catalyst. Amino acids are transformed into their corresponding amides without racemization, and the catalyst displays full selectivity for the amidation of carboxylic acids over esters. Electronic properties of the carboxylic acids were found to have a strong influence on the rate of the amidation reaction, and the need for a balanced amount of molecular sieves was observed to be highly important for optimal reaction outcome.

Catalytic chemical amide synthesis at room temperature: One more step toward peptide synthesis

An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic, α-hydroxyl, aromatic, and heteroaromatic acids as well as primary, secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected amino acids were successfully coupled in good yields with very little racemization. An example of catalytic dipeptide synthesis is reported.

Ammonium nitrate: A biodegradable and efficient catalyst for the direct amidation of esters under solvent-free conditions

A simple, metal-free, and environment-friendly procedure is developed for the direct conversion of esters to amides using ammonium nitrate as a catalyst under solvent-free conditions. Aryls, heteroaryls, and aliphatic esters are easily converted to the corresponding amides in excellent isolated yields (85-99%). An enantiopure ester and amine were both shown to react without racemization. The methodology has been successfully applied to preparation of procainamide.