80099-99-6

Upstream product

• 109-09-1 2-chloropyridine 
• 611-74-5 N,N-dimethylbenzamide 
• 2402-78-0 2,6-dichloropyridine 
• 74714-04-8 2-chloro-6-benzyl-pyridine 
• 62673-31-8 benzyl(bromo)zinc 
• 20531-86-6 2-benzylpyridine-N-oxide 
• 4789-06-4 (1-oxido-2-pyridinyl)phenylmethanone 
• 140-29-4 phenylacetonitrile 
• 201230-82-2 carbon monoxide 
• 98-80-6 phenylboronic acid 
• 24783-42-4 (6-Chloro-pyridin-2-yl)-phenyl-acetonitrile 

Downstream Products

• 177962-18-4 7-Chloro-3-phenyl-1,2,3-triazolo[1,5-a]pyridine 

Relevant academic research and scientific papers

Overcoming Electron-Withdrawing and Product-Inhibition Effects by Organocatalytic Aerobic Oxidation of Alkylpyridines and Related Alkylheteroarenes to Ketones

An organocatalyzed aerobic benzylic C-H oxidation of alkyl and aryl heterocycles has been developed. This transition metal-free method is able to overcome the electron-withdrawing effect as well as product-inhibition effects in heterobenzylic radical oxidation. A variety of ketones bearing N-heterocyclic groups could be prepared under relatively mild conditions with moderate to high yields.

Copper-Catalyzed Aerobic Oxygenation of Benzylpyridine N-Oxides and Subsequent Post-Functionalization

A copper-catalyzed aerobic oxidation of benzylpyridine N-oxides is reported. The N-oxide moiety acts as a built-in activator for the benzylic methylene oxidation, without requirement of additives. Reaction conditions were identified which suppress undesired benzoylpyridine formation via N-deoxygenation involving intermolecular oxygen transfer. The versatility of the N-oxide group of the benzoylpyridine N-oxide reaction products for post-functionalization of the pyridine ring is demonstrated through efficient C–C, C–N, C–O and C–Cl bond forming procedures, with both nucleophiles and electrophiles. Finally, the applicability of the new synthetic methodology is demonstrated in an alternative route towards the antihistaminic drug Acrivastine via three consecutive N-oxide activated C–H functionalization processes, starting from picoline N-oxide. (Figure presented.).

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP-MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.

Palladium-N-heterocyclic carbene an efficient catalytic system for the carbonylative cross-coupling of pyridine halides with boronic acids

Carbonylative cross-coupling of different pyridyl halides with various boronic acids was studied using catalytic systems constituted of N-heterocyclic carbene type ligands and palladium. These systems easily obtained in situ from the corresponding imidazolium salt and palladium acetate appear more efficient toward bromopyridines than catalysts based on hindered and basic alkylphosphines such as tricyclohexylphosphine. Their higher efficiency was also evidenced by coupling using chloro- or dichloropyridines and chloroquinolines, which practically do not react with catalytic systems based on phosphines.

TMSCH2Li-LiDMAE: a new nonnucleophilic reagent for C-2 lithiation of halopyridines

A new superbasic reagent has been discovered by combining TMSCH2Li and LiDMAE in hexane. This reagent was found highly efficient for the C-2 lithiation of sensitive chloro- and fluoropyridines. The metallation occurred chemo- and regioselectively at 0 °C avoiding the nucleophilic addition or substrate degradation commonly obtained with other alkyllithiums even at lower temperatures.

Palladium-catalyzed carbonylative coupling of pyridine halides with aryl boronic acids

The carbonylative Suzuki cross-coupling of a variety of mono-iodopyridines and bromopyridines (1a,b, 3a-c, 5) catalyzed by palladium-phosphane systems has been studied to prepare benzoylpyridine derivatives (2, 4, 6). The selectivity and the rate of the reaction are highly dependent on the reaction conditions, i.e. nature of the palladium catalyst precursor, solvent, temperature and CO pressure. The main side-products arise from direct, non-carbonylative cross-coupling. Under optimized conditions, benzoylpyridines are recovered in high yields (80-95%). The order of reactivity decreases from iodo- to bromopyridines and from 2-, 4- to 3-substituted halopyridines. The reactivity of dihalopyridines has been investigated; 2,6-dibromopyridine (7) and 3,5-dibromopyridine (11) are selectively transformed into either the corresponding benzoyl-phenylpyridine (8, 12) or the corresponding dibenzoylpyridine (9, 13). Dissymmetric 2,5-dihalopyridines (15a,b) are transformed into 2-benzoyl-5-bromopyridine (16) or 2,5-dibenzoylpyridine (17) in high yields.

Direct Synthesis of Benzoylpyridines from Chloropyridines via a Palladium-Carbene Catalyzed Carbonylative Suzuki Cross-Coupling Reaction

The use of N-heterocyclic carbene-type ligands with palladium catalysts allows the activation of chloropyridines and chloroquinoline towards carbonylative cross-coupling with phenylboronic acid for the synthesis of unsymmetrical biaryl ketones.

Unusual C-6 lithiation of 2-chloropyridine-mediated by BuLi-Me2N(CH2)2OLi. New access to 6-functional-2-chloropyridines and chloro-bis-heterocycles

Formula Presented The reaction of 2-chloropyridine with alkylithium generally results in nucleophilic addition leading to the loss of chlorine atom while exclusive directed ortho metalation is obtained using LDA. Herein it is shown that the BuLi-Me2

A New Synthesis of Aryl Hetaryl Ketones via SRN1 Reaction of Halogenated Heterocycles withPotassiophenylacetonitrile Followed by Phase-Transfer Catalyzed Decyanation

Reaction of halogenated pyridines, quinolines, pyrimidines, and pyrazines with potassiophenylacetonitrile (5) in liquid ammonia under near-uv irradiation affords secondary nitriles, which then undergo oxidative decyanation under phase-transfer catalytic conditions to afford aryl hetaryl ketones in excellent yields.