7556-56-1

Upstream product

• 109-01-3 1-methyl-piperazine 
• 98-88-4 benzoyl chloride 
• 110-85-0 piperazine 
• 74-88-4 methyl iodide 
• 100-52-7 benzaldehyde 
• 616-38-6 carbonic acid dimethyl ester 
• 13754-38-6 N-Benzoylpiperazine 
• 7334-48-7 benzoic (diethyl phosphoric) anhydride 
• 88070-48-8 N-methylbenzamide 
• 63412-06-6 N-methyl-N-nitrosobenzamide 
• 50-00-0 formaldehyd 
• 120-51-4 benzoic acid benzyl ester 
• 108-88-3 toluene 
• 100-51-6 benzyl alcohol 

Downstream Products

• 57238-77-4 4-benzoyl-1-piperazinecarboxaldehyde 
• 62226-74-8 1-benzyl-4-methylpiperazine 
• 63833-46-5 ethyl 5-benzoyl-2,4-dimethylpyrrole-3-carboxylate 

Relevant academic research and scientific papers

Two-step continuous flow synthesis of amide via oxidative amidation of methylarene

A green and efficient method for the synthesis of amides has been developed through oxidative amidation between methylarenes with amines in a two-step continuous flow system. This method integrates methylarene oxidation and amide formation into a single operation which is usually accomplished separately. Oxidation with tert-butyl hydroperoxide (TBHP) as “green” oxidant, the synthesis of amides under mild reaction conditions in continuous flow system and the utilization of methylarenes as starting material make this methodology novel and environment friendly. The practical value of this method is highlighted through the synthesis of high-profile pharmaceutical agents, acetylprocainamide.

Methyl-Selective α-Oxygenation of Tertiary Amines to Formamides by Employing Copper/Moderately Hindered Nitroxyl Radical (DMN-AZADO or 1-Me-AZADO)

Methyl-selective α-oxygenation of tertiary amines is a highly attractive approach for synthesizing formamides while preserving the amine substrate skeletons. Therefore, the development of efficient catalysts that can advance regioselective α-oxygenation at the N-methyl positions using molecular oxygen (O2) as the terminal oxidant is an important subject. In this study, we successfully developed a highly regioselective and efficient aerobic methyl-selective α-oxygenation of tertiary amines by employing a Cu/nitroxyl radical catalyst system. The use of moderately hindered nitroxyl radicals, such as 1,5-dimethyl-9-azanoradamantane N-oxyl (DMN-AZADO) and 1-methyl-2-azaadamanane N-oxyl (1-Me-AZADO), was very important to promote the oxygenation effectively mainly because these N-oxyls have longer life-times than less hindered N-oxyls. Various types of tertiary N-methylamines were selectively converted to the corresponding formamides. A plausible reaction mechanism is also discussed on the basis of experimental evidence, together with DFT calculations. The high regioselectivity of this catalyst system stems from steric restriction of the amine-N-oxyl interactions.

Tert -Butyl nitrite promoted transamidation of secondary amides under metal and catalyst free conditions

A mild and efficient method is demonstrated for the transamidation of secondary amides with various amines including primary, secondary, cyclic and acyclic amines in the presence of tert-butyl nitrite. The reaction proceeds through the N-nitrosamide intermediate and provides the transamidation products in good to excellent yields at room temperature. Moreover, the developed methodology does not require any catalyst or additives.

Cross-Dehydrogenating Coupling of Aldehydes with Amines/R-OTBS Ethers by Visible-Light Photoredox Catalysis: Synthesis of Amides, Esters, and Ureas

A straightforward synthesis of amides, ureas, and esters is reported by visible-light cross-dehydrogenating coupling (CDC) of aldehydes (or amine carbaldehydes) and amines/R-OTBS ethers by photoredox catalysis. The reaction is found to be general and high yielding. A plausible mechanistic pathway has been proposed for these transformations and is supported by appropriate controlled experiments.

Manganese-Catalyzed Direct Conversion of Ester to Amide with Liberation of H2

A simple and efficient Mn-catalyzed acylation of amines is achieved using both acyl and alkoxy functions of unactivated esters with the liberation of molecular hydrogen as a sole byproduct. The present protocol provides an atom-economical and sustainable route for the synthesis of amides from esters by employing an earth-abundant manganese salt and inexpensive phosphine-free tridentate ligand.

Loss of benzaldehyde in the fragmentation of protonated benzoylamines: Benzoyl cation as a hydride acceptor in the gas phase

In electrospray ionization tandem mass spectrometry of protonated 1-benzoylamines (1-benzoylpiperadine, 1-benzoylmorpholine, and 1-benzoyl-4-methylpiperazine), the dominant fragmentation pathway was amide bond cleavage to form benzoyl cation and neutral amine. Meanwhile, in their fragmentations, an interesting loss of benzaldehyde (106?Da) was observed and identified to derive from hydride transfer reaction between the benzoyl cation and amine. A stepwise mechanism for loss of 106?Da (benzene and CO) could be excluded with the aid of deuterium labeling experiment. Theoretical calculations indicated that hydride transfers from amines (piperadine, morpholine, and 1-methylpiperazine) to benzoyl cation were thermodynamically permitted, and 1-methylpiperazine was the best hydride donor among the 3 amines. The mass spectrometric experimental results were consistent with the computational results. The relative abundance of the iminium cation (relative to the benzoyl cation) in the fragmentation of protonated 1-benzoyl-4-methylpiperazine was higher than that in the fragmentation of the other 2 protonated 1-benzoylamines. By comparing the fragmentations of protonated 1-benzyl-4-methylpiperazine and protonated 1-benzoyl-4-methylpiperazine and the energetics of their hydride transfer reactions, this study revealed that benzoyl cation was a hydride acceptor in the gas phase, but which was weaker than benzyl cation.

Copper-catalyzed one-pot oxidative amidation between methylarenes and amines

A new method for the direct one-pot oxidative amidation between methylarenes and amines catalyzed by copper has been developed. This method integrates methylarene oxidation and amide bond formation, which are usually accomplished separately, into a single operation. In addition, the reaction provides a relatively high yield and has a wide substrate scope. Moreover, the starting reagents are abundant and available in a convenient way at a cheaper price.

Direct oxidative amination of aromatic aldehydes with amines in a continuous flow system using a metal-free catalyst

A novel method for metal-free oxidative amination of aromatic aldehydes and alcohols in the presence of H2O2/NaBr/H+ within 25 min in a continuous flow system has been developed. A series of different substrates were tested and the corresponding products were obtained in good yields .

Copper-catalyzed one-pot oxidative amidation of alcohol to amide via C-H activation

A one-pot oxidative amidation of both aliphatic and aromatic alcohols with N-chloramines, prepared in situ from many types of primary and secondary amines, was developed. This cross-coupling reaction integrates alcohol oxidation and amide bond formation, which are usually accomplished separately, into a single operation. And it was green, simple and convenient, which has a wide substrate scope and makes use of cheap, abundant, and easily available reagents. The practical value of this method is highlighted through the synthesis of a high-profile pharmaceutical agent, acetylprocainamide.

Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions

NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.