22164-12-1

Upstream product

• 618-36-0 rac-methylbenzylamine 
• 2719-27-9 cyclohexanylcarbonyl chloride 
• 4630-82-4 methyl cyclohexylcarboxylate 
• 3289-28-9 ethyl cyclohexanecarboxylate 
• 110-82-7 cyclohexane 
• 201230-82-2 carbon monoxide 
• 2627-86-3 (S)-1-phenyl-ethylamine 
• 1239906-37-6 C₇H₁₂BrNO₂ 
• 98-85-1 1-Phenylethanol 
• 766-05-2 cyclohexane carbonitrile 
• 98-89-5 Cyclohexanecarboxylic acid 
• 1977-87-3 cyclohexanecarbonyl fluoride 
• 80283-44-9 4-hydroxyphenyl cyclohexanecarboxylate 

Downstream Products

• 128037-39-8 Acetic acid 3-[cyclohexanecarbonyl-(1-phenyl-ethyl)-amino]-2,2-dimethyl-3-oxo-propyl ester 
• 1623-51-4 α-Phenethylcarbamidsaeureethylester 
• 128037-43-4 N-1-phenethylhydroxypivalamide 
• 618-36-0 rac-methylbenzylamine 
• 98-89-5 Cyclohexanecarboxylic acid 
• 766-05-2 cyclohexane carbonitrile 

Relevant academic research and scientific papers

Parallel Synthesis of 1H-Pyrazolo[3,4-d]pyrimidines via Condensation of N-Pyrazolylamides and Nitriles

A novel parallel medicinal chemistry (PMC)-enabled synthesis of 1H-pyrazolo[3,4-d]pyrimidines employing condensation of easily accessible N-pyrazolylamides and nitriles has been developed. The presented studies describe singleton and library enablements that allowed rapid generation of molecular diversity to examine C4 and C6 vectors. This chemistry enabled access to challenging alkyl substituents, expanding the overall chemical space beyond that available via typical C(sp2)-C(sp2) coupling and SNAr transformations. Furthermore, monomer group interconversions allowing the use of larger and more diverse amides and carboxylic acids as precursors to nitriles are discussed.

Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis

A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.

Tropylium-promoted Ritter reactions

The Ritter reaction used to be one of the most powerful synthetic tools to functionalize alcohols and nitriles, providing valuableN-alkyl amide products. However, this reaction has not been frequently used in modern organic synthesis due to its employment of strongly acidic and harsh reaction conditions, which often lead to complicated side reactions. Herein, we report the development of a new method using salts of the tropylium ion to promote the Ritter reaction. This method works well on a range of alcohol and nitrile substrates, giving the corresponding products in good to excellent yields. This reaction protocol is amenable to microwave and continuous flow reactors, offering an attractive opportunity for further applications in organic synthesis.

An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines

We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.

Nickel-catalyzed transamidation of aliphatic amide derivatives

Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C-N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date.

Copper-Catalyzed Carbonylative Synthesis of Aliphatic Amides from Alkanes and Primary Amines via C(sp3)-H Bond Activation

Amides are important intermediates and building blocks in organic synthesis. Among the known preparation procedures, aminocarbonylation is an interesting and powerful tool. However, most of the studies were focused on noble metal-catalyzed synthesis of ar

Microwave-promoted direct amidation of unactivated esters catalyzed by heteropolyanion-based ionic liquids under solvent-free conditions

Abstract A simple and efficient procedure for the synthesis of amides directly from unactivated esters and amines catalyzed by heteropolyanion-based ionic liquids under microwave-promoted and solvent-free conditions has been reported. The practical protocol was found to be compatible with different structurally diverse substrates. Moderate to excellent yields, solvent-free media, and operational simplicity are the main highlights. Furthermore, the heteropolyanion-based ionic liquids were easily reusable for this amidation.

Discovery of competing anaerobic and aerobic pathways in umpolung amide synthesis allows for site-selective amide18O-labeling

The mechanism of umpolung amide synthesis was probed by interrogating potential sources for the oxygen of the product amide carbonyl that emanates from the α-bromo nitroalkane substrate. Using a series of 18O-labeled substrates and reagents, evidence is gathered to advance two pathways from the putative tetrahedral intermediate. Under anaerobic conditions, a nitro-nitrite isomerization delivers the amide oxygen from nitro oxygen. The same homolytic nitro-carbon fragmentation can be diverted by capture of the carbon radical intermediate with oxygen gas (O2) to deliver the amide oxygen from O2. This understanding was used to develop a straightforward protocol for the preparation of 18O-labeled amides in peptides by simply performing the umpolung amide synthesis reaction under an atmosphere of 18O2.

Self-disproportionation of enantiomers of non-racemic chiral amine derivatives through achiral chromatography

Efficient self-disproportionation of enantiomers of several non-racemic chiral amines was achieved through conversion to N-acetamides and subsequent MPLC using an achiral column. The MPLC of these non-racemic N-acetamide derivatives gave the chart having a clear boundary between two fractions. Thus, in the less polar fraction, remarkable enantiomer enrichment was observed (>99%ee), while the ee of more polar fraction was considerably reduced. The magnitude of the enantiomer enrichments and depletions strongly depended on substituent on the amino group.

Silica boron-sulfuric acid nanoparticles (SBSANs): Preparation, characterization and their catalytic application in the Ritter reaction for the synthesis of amide derivatives

Among a number of different heterogeneous and homogeneous catalysts, silica boron-sulfuric acid nanoparticles (SBSANs) with both protic and Lewis acidic sites were shown to be the most active and recyclable catalyst in the Ritter reaction. Various amide d