5692-34-2

Upstream product

• 463-72-9 carbamic chloride 
• 106-42-3 para-xylene 
• 72371-42-7 2,5-Dimethyl-benzoyl-nitril 
• 1118-02-1 trimethylsilyl isocyanate 
• 143814-17-9 2,6-dicyanatoanthraquinone 
• 51-79-6 urethane 
• 4044-60-4 2,5-dimethylbenzophenone 
• 71-43-2 benzene 
• 5779-94-2 2,5-dimethylbenzaldehyde 
• 127099-85-8 N-Cyanoguanidine 
• 74331-70-7 2-ethynyl-1,4-dimethylbenzene 
• 75840-13-0 2-bromo-1-(2,5-dimethylphenyl)ethan-1-one 
• 201230-82-2 carbon monoxide 
• 95-72-7 2-chloro-1,4-dimethyl-benzene 

Downstream Products

• 2050-44-4 N-(2,5-dimethylphenyl)acetamide 
• 1630983-16-2 2,5-bis(difluoromethyl)benzamide 

Relevant academic research and scientific papers

Cobalt-catalysed C–H methylation for late-stage drug diversification

The magic methyl effect is well acknowledged in medicinal chemistry, but despite its significance, accessing such analogues via derivatization at a late stage remains a pivotal challenge. In an effort to mitigate this major limitation, we here present a strategy for the cobalt-catalysed late-stage C–H methylation of structurally complex drug molecules. Enabling broad applicability, the transformation relies on a boron-based methyl source and takes advantage of inherently present functional groups to guide the C–H activation. The relative reactivity observed for distinct classes of functionalities were determined and the sensitivity of the transformation towards a panel of common functional motifs was tested under various reaction conditions. Without the need for prefunctionalization or postdeprotection, a diverse array of marketed drug molecules and natural products could be methylated in a predictable manner. Subsequent physicochemical and biological testing confirmed the magnitude with which this seemingly minor structural change can affect important drug properties. [Figure not available: see fulltext.]

Mechanistic Studies of Palladium-Catalyzed Aminocarbonylation of Aryl Chlorides with Carbon Monoxide and Ammonia

Mechanistic information on a reliable, palladium-catalyzed aminocarbonylation of aryl chlorides with ammonia is reported. The reaction occurs with ethylene complex 1 as catalyst, and mechanistic information was gained by isolation of catalytic intermediates and kinetic measurements, including the first mechanistic data on the oxidative addition of aryl chloride to a palladium(0) complex in the presence of CO. Arylpalladium and phenacylpalladium halide intermediates were synthesized, and kinetic measurements of the formation and reactions of these intermediates were undertaken to determine the mechanism of the oxidative addition of aryl bromides and chlorides to a Pd(0) dicarbonyl compound in the presence of CO and the mechanism of the reaction of ammonia with a Pd(II) phenacyl complex to form benzamide. The oxidative addition of aryl chlorides and aryl bromides was determined to occur with rate-limiting reaction of the haloarene with a three-coordinate Pd(0) species bearing a bidentate phosphine and one CO ligand. A primary 13C kinetic isotope effect suggested that this step involves cleavage of the carbon-halogen bond. Our data show that the formation of benzamide from the reaction of phenacylpalladium halide complexes with ammonia occurs by a pathway involving reversible displacement of chloride from a phenacylpalladium chloride complex by ammonia, deprotonation of the bound ammonia to form a phenacylpalladium amido complex, and reductive elimination to form the C-N bond. Consistent with this mechanism, the reaction of an aryl palladium amido complex with CO formed the corresponding primary benzamide. A catalyst deactivation pathway involving the formation of a Pd(I) dimer also was elucidated.

One-Pot Preparation of Aromatic Amides, 4-Arylthiazoles, and 4-Arylimidazoles from Arenes

Simple treatment of arenes with α-bromoacetyl chloride and AlCl3, followed by the reaction with molecular iodine and aq. NH3, thioamides, or amidines gave the corresponding primary aromatic amides, 4-arylthiazoles, or 4-arylimidazoles in good yields, respectively. Aryl α-bromomethyl ketones are the key intermediates in those reactions. Primary aromatic amides were formed from arenes through the reaction of aryl α-bromomethyl ketones with molecular iodine and aq. NH3, and 4-arylthiazoles and 4-arylimidazoles were formed from arenes through the reactions of aryl α-bromomethyl ketones with thioamides and amidines, respectively, in one pot under transition-metal-free conditions.

Visible Light-Induced Iodine-Catalyzed Transformation of Terminal Alkynes to Primary Amides via C≡C Bond Cleavage under Aqueous Conditions

The visible light-induced iodine-catalyzed oxidative cleavage of the C≡C bond for transforming terminal alkynes into primary amides in the presence of ammonia under aqueous conditions is described. This metal-free protocol which ensued via initial hydroamination of the acetylene bond followed by liberation of diiodomethane (CH2I2) was found to be applicable to aromatic, heteroaromatic and aliphatic alkynes.

Benzamide synthesis by direct electrophilic aromatic substitution with cyanoguanidine

Cyanoguanidine is an inexpensive commodity chemical and it is found to be a useful reagent for the direct Friedel-Crafts carboxamidation of arenes. The reaction works best in an excess of Bronsted superacid, an observation suggesting the involvement of a superelectrophilic intermediate. Theoretical calculations indicate that the most stable diprotonated species involves protonation at the guanidine and cyano nitrogen atoms.

A mild and expeditious synthesis of amides from aldehydes using bio glycerol-based carbon as a recyclable catalyst

The new bioglycerol-based carbon catalyst acts as an efficient, readily available, and reusable catalyst for the synthesis of amides, when aldehyde and hydroxylamine hydrochloride react in acetonitrile.

A new modified electrophilic cyanation of aromatics with activated aryl cyanates

The selective cyanation of electron-rich aromatics succeeds in moderate to good yields with the activated aryl cyanates 1a-d using AlCl3/HCl. The formation of p-isomeres is preferred.