41208-51-9

Upstream product

• 87802-71-9 (E)-methyl cinnamyl carbonate 
• 68-12-2 N,N-dimethyl-formamide 
• 1821-12-1 4-Phenylbutyric acid 
• 110-89-4 piperidine 
• 18496-54-3 phenylbutyric acid chloride 
• 16520-62-0 4-Phenyl-1-butyne 
• 6091-44-7 piperidine hydrochloride 
• 162147-97-9 1-chloro-4-phenyl-1-(phenylsulfinyl)-2-butanone 
• 201230-82-2 carbon monoxide 

Downstream Products

• 3056-71-1 N-phenyl-4-phenylbutyramide 

Relevant academic research and scientific papers

Selective α-Oxyamination and Hydroxylation of Aliphatic Amides

Compared to the α-functionalization of aldehydes, ketones, even esters, the direct α-modification of amides is still a challenge because of the low acidity of α-CH groups. The α-functionalization of N?H (primary and secondary) amides, containing both an unactived α-C?H bond and a competitively active N?H bond, remains elusive. Shown herein is the general and efficient oxidative α-oxyamination and hydroxylation of aliphatic amides including secondary N?H amides. This transition-metal-free chemistry with high chemoselectivity provides an efficient approach to α-hydroxy amides. This oxidative protocol significantly enables the selective functionalization of inert α-C?H bonds with the complete preservation of active N?H bond.

Direct amide formation in a continuous-flow system mediated by carbon disulfide

Amide bonds are ubiquitous in nature. They can be found in proteins, peptides, alkaloids, etc. and they are used in various synthetic drugs too. Amide bonds are mainly made by the use of (i) hazardous carboxylic acid derivatives or (ii) expensive coupling agents. Both ways make the synthetic technology less atom economic. We report a direct flow-based synthesis of amides. The developed approach is prominently simple and various aliphatic and aromatic amides were synthetized with excellent yields. The reaction in itself is carried out in acetonitrile, which is considered as a less problematic dipolar aprotic solvent. The used coupling agent, carbon disulfide, is widely available and has a low price. The utilized heterogeneous Lewis acid, alumina, is a sustainable material and it can be utilized multiple times. The technology is considerably robust and shows excellent reusability and easy scale-up is carried out without the need of any intensive purification protocols.

Direct use of dioxygen as an oxygen source: Catalytic oxidative synthesis of amides

The first transition-metal-catalyzed direct oxidative synthesis of amides by using dioxygen as an oxygen source has been developed under mild conditions, in which DBU was used as the key additive. The present methodology, which utilizes dioxygen as an oxidant and oxygen source and cheap copper salts as catalysts, opens up an interesting and attractive avenue for the synthesis of amide functionality.

The uncatalyzed direct amide formation reaction - Mechanism studies and the key role of carboxylic acid h-bonding

Calorimetric studies of the mixing of a series of carboxylic acids and amines have been carried out to measure heat output, which has been compared with their ability to react to form carboxylate ammonium salts and amides. In order to identify which species (salt or H-bonded species) were formed, 1H NMR studies were also carried out by mixingcarboxylic acids and amines in [D8]toluene and monitoring the resulting reactions. These experiments were also compared to DFT computational studies, from which the relative merits of different mechanistic schemes for direct amide formation could be assessed. A reaction mechanism involving zwitterionic intermediates could be eliminated on the basis of calculated energies in toluene, however, a neutral intermediate pathway, involving carboxylic acid dimerization by mutual hydrogen bonding was found to be accessible and may explain how the direct amide formation reaction occurs. Such a mechanism is not inconsistent with kinetic modelling of direct amide formation under different reactions conditions. It Takes Two to Amide: Direct amide formation between carboxylic acids andamines has attracted a lot of curiosity, but there is little clarification on the interplay between ammonium carboxylate salt formation vs. amide bond formation. These studies shed light on these competing processes and a new mechanism is proposed for direct amide formation, elucidating the key role of carboxylic acid dimers.

Ligand exchange reaction of sulfoxides in organic synthesis: A versatile procedure for one-carbon homologation of methylesters to esters, thioesters, carboxylic acids and amides

A novel two-step procedure for one-carbon homologation of methylesters to esters, thioesters, carboxylic acids and amides is described. Methylesters are reacted with lithium carbanion of chloromethyl phenyl sulfoxide to give α-chloro α-sulfinyl ketones in 70 to 90% yields. Potassium enolate of the α-chloro α-sulfinyl ketone was treated with tert-butyllithium at -78°C to give alkynolate via alkylidene carbenoid. This intermediate was treated with alcohols, thioles, 5% aqueous NaOH, and amine hydrochlorides to afford one-carbon homologated esters, thioesters, carboxylic acids and amides, respectively, in good to excellent yields.

Ruthenium Complex-Catalyzed Carbonylation of Allylic Compounds

Allylic alkyl carbonates are carbonylated under 40 atm of carbon monoxide at 100-120 deg C in the presence of a catalytic amount of Ru3(CO)12/1,10-phenanthroline to give α,β- or β,γ-unsaturated esters in good to high yields.For example, cinnamyl methyl carbonate afforded the corresponding β,γ-unsaturated esters, methyl trans-4-phenyl-3-butenoate (1) in 93percent yield.The regioselectivity in the carbonylation of crotyl methyl carbonate is unusual and it depends on the carbon monoxide pressure.The more sterically hindered carbon (γ-carbon) is predominantly carbonylated at 20-50 atm.When the reaction of cinnamyl methyl carbonate was performed at elevated temperature (150 deg C) without 1,10-phenanthroline, the dimer of 1, dimethyl 3-benzyl-2-(trans-2-phenylvinyl)glutarate, was obtained in 56percent yield.In the presence of secondary amines, allylic alkyl carbonates were carbonylated mainly at α-carbon to give α,β- or β,γ-unsaturated amides in high yields.