2-pyridyl Ketones Research Articles

Unusual and Persistent Free Radical Intermediate Production from 2-Pyridyl Ketones via UV Irradiation: A Direct ESR Study.

Aryl ketones are often used as photosensitizers and photoinitiators. Free radical intermediates have been suggested, but not confirmed, to be generated after photoirradiation. Here we found, unexpectedly, that a persistent radical was produced from di-2-pyridyl ketone after UV irradiation, which was detected by the direct ESR method. Interestingly, the persistent radical was very sensitive to oxygen and the pH of the reaction medium. A similar persistent radical was also observed from phenyl-2-pyridyl ketone, but not from 3-benzoylpyridine, 4-benzoylpyridine, and benzophenone, suggesting that the presence of a carbonyl group connected to the ortho-position of the pyridine ring is critical for such radical production. By complementary applications of ESR, HPLC, and ESI-Q-TOF-MS, the possible chemical structures of the persistent radical and final product were identified, and the possible underlying reaction mechanism was proposed. This represents the first report on UV-induced persistent radical generation from 2-pyridyl ketones, which should be of great significance for future studies.

Cobalt-Catalyzed Chemoselective Reduction of N-Heteroaryl Ketones with N,N-Dimethylformamide as a Hydride Source.

A method for chemoselective reduction of 2-pyridyl ketones and related N-heteroaryl compounds catalyzed by cobalt stearate using DMF as a hydride source is developed. The ketone substrate is activated by chelation with cobalt, which makes the present method highly chemoselective. A possible reaction mechanism is proposed on the basis of control experiments.

Practical and rapid construction of 2-pyridyl ketone library in continuous flow

2-Pyridyl ketones widely appear in bioactive molecules, natural products, and are employed as precursors of chiral 2-pyridine alky/aryl alcohols or 2-aminoalkyl pyridine ligands for asymmetric catalysis. Herein, a practical method for the rapid synthesis of 2-pyridyl ketone library in continuous flow is reported, in which the 2-lithiopyridine formed by Br/Li exchange reacts with commercially available esters to obtain 2-pyridyl ketones in a good yield at short reaction time. This protocol functions broadly on a variety of esters and has been applied to the synthesis of TGF-β type 1 receptor inhibitor LY580276 intermediate in an environmentally friendly method. It is rapid, reliable, and cost-efficient to afford diverse kinds of 2-pyridyl ketones in the compound library.

Mg3N2-assisted one-pot synthesis of 1,3-disubstituted imidazo[1,5-a]pyridine.

A novel Mg3N2-assisted one-pot annulation strategy has been developed via cyclo-condensation reaction of 2-pyridyl ketones with alkyl glyoxylates or aldehydes, allowing the formation of imidazo[1,5-a]pyridines exclusively with an exellent yield.

Ruthenium-catalyzed meta-C-H bond alkylation of aryl 2-pyridyl ketones.

The first example of meta-selective CAr-H bond functionalization of aryl 2-pyridyl ketones has been developed using [Ru(p-cymene)Cl2]2 as the catalyst and alkyl bromide as the coupling reagent. This development provides an efficient strategy for modifying the meta-position of aryl 2-pyridyl ketone skeletons, which are found in various functional molecules.

Highly Enantioselective Hydrogenation of Non-ortho-Substituted 2-Pyridyl Aryl Ketones via Iridium-f-Diaphos Catalysis.

This work disclosed a highly enantioselective hydrogenation of non-ortho-substituted 2-pyridyl aryl ketones via Ir/f-diaphos catalysis. This catalytic system allows for full control over the configuration of the stereocenter, affording two enantiomers of the desired products with extremely high enantioselectivity (up to >99% ee in most cases) and excellent reactivity (TON of up to 19600, TOF of 1633 h-1) under mild conditions. Density functional theory calculations and control experiments revealed that the relay hydrogen bonding among the solvent isopropanol, substrate, and ligand is crucial for high ee's.

Synthesis of imidazo[1,5-a]pyridines via I2-mediated sp3 C-H amination.

A transition-metal-free sp3 C-H amination reaction has been established for imidazo[1,5-a]pyridine synthesis employing molecular iodine from 2-pyridyl ketones and alkylamines. In the presence of sodium acetate (NaOAc), the I2-mediated oxidative annulations of readily available substrates produced a variety of imidazo[1,5-a]pyridine derivatives efficiently in a one-pot manner. The present synthetic approach is operationally simple and can be conveniently carried out on a gram scale. Moreover, under the optimal reaction conditions a series of 1-(2-pyridyl)imidazo[1,5-a]pyridine cysteine protease inhibitors were easily prepared from the corresponding di-2-pyridyl ketones and substituted benzylamines in satisfactory yields.

Synthesis of Indolizine Derivatives Utilizing [1,2]-Phospha-Brook Rearrangement/Cycloisomerization Sequence

A new synthesis of indolizine derivatives was developed by utilizing the [1,2]-phospha-Brook rearrangement under Bronsted base catalysis. The method involves the generation of allenylpyridine from alkynyl 2-pyridyl ketones through the [1,2]-phospha-Brook rearrangement and the following cycloisomerization without using transition-metal catalysts. The method can be performed in a one-pot fashion and directly provides indolizine derivatives having a phosphate moiety that can function as a handle for further manipulation.

‘Wake-Up Call of A Sleeping Beauty’: Straightforward Synthesis of Functionalized β-(2-Pyridyl) Ketones from 2,6-Lutidine

β-(2-Pyridyl) ketones are a unique class of heterocycles with valuable physicochemical properties and emerging relevance as pharmacophores. Herein we report a one-step process for the preparation of various substituted β-(2-pyridyl) ketones from the common starting material, 2,6-lutidine. Furthermore, we demonstrate the utility of this building block by synthesizing of a small set of antimalarial natural products.

Chiral Phosphoric Acid-Catalyzed Enantioselective Reductive Amination of 2-Pyridyl Ketones: Construction of Structurally Chiral Pyridine-Based Ligands.

A chiral phosphoric acid-catalyzed one-pot enantioselective reductive amination of 2-pyridyl ketones was realized to provide chiral pyridine-based ligands in excellent yields with high enantioselectivities (up to 98% yield, 94% ee). Computational studies on the key intermediate imine and transition state of the hydride transfer process revealed that the nitrogen atom of the pyridyl ring might be an important factor to significantly promote both the reaction activity and enantioselectivity.

Chiral Lewis Acid Catalyzed Enantioselective Conjugate Radical Additions to α,β-Unsaturated 2-Pyridyl Ketones

We have investigated the utility of a pyridine-based achiral template in enantioselective conjugate radical additions.

Diastereoselective reduction of enantiopure N- p-toluenesulfinyl ketimines derived from pyridyl ketones

DIBAL reduction of enantiopure N- p-toluenesulfinyl ketimines derived from 2-pyridyl ketones bearing an additional substituent on the 6-position of the pyridine ring afforded the related N- p-toluenesulfinyl amines with high yields and diastereoselectivities. The results of a number experiments exploring the conversion of a optically active 1-substituted N-toluenesulfinyl 1-(6-bromopyridin-2-yl)methylamine in a number of more complex pyridine derivatives with maintenance of the toluenesulfinyl group N-protecting group is also reported.

Asymmetric Synthesis of 1‐Substituted‐1‐(pyridin‐2‐yl)methylamines by Diastereoselective Reduction of Enantiopure N‐p‐toluenesulfinyl Ketimines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric synthesis of 1-substituted-1-(pyridin-2-yl)methylamines by diastereoselective reduction of enantiopure N- p-toluenesulfinyl ketimines

Reduction of enantiopure N- p-toluenesulfinyl ketimines derived from 2-pyridyl ketones affords N- p-toluenesulfinyl amines with good yields and diastereoselectivities.

Eight-coordination in nitrato manganese(II) complexes with tetradentate di-Schiff bases derived from 2-pyridyl ketones: preparation, characterization and catalytic activity for alkene epoxidation

The reactions of Mn(NO 3) 2·6H 2O with the tetradentate Schiff bases N, N′-bis[1-(pyridin-2-yl)ethylidene]ethane-1,2-diamine (L A) and N, N′-bis[1-(pyridin-2-yl)benzylidene]ethane-1,2-diamine (L B) afforded the novel eight-coordinate complexes [Mn(NO 3) 2(L A)] ( 1) and [Mn(NO 3) 2(L B)] ( 2), which have a distorted dodecahedral coordination geometry. The catalytic activity of 1 and 2 for alkene epoxidation is reported and discussed.

Applications of organolithium and related reagents in synthesis. Part 3. A general study of the reaction of lithium alkyls with pyridine ketones

The reaction of MeLi and PhLi with acetylpyridines (1a–c) and their annelated derivatives (2a), (2b), (3), and (4) has been examined. The 3- and 4-pyridyl ketones (1b), (1c), (3), and (4) gave similar results to acetophenone and 3,4-dihydronaphthalen-1(2H)-one. In the case of the 2-pyridyl ketones (1a), (2a), and (2b) unexpectedly low yields of products resulted from the addition of RLi to the carbonyl group; the reaction was efficiently enhanced by initially adding an additional amount of LiBr. These results were accounted for by the chelation of RLi or LiBr by the 2-pyridyl ketones.

Synthesis and insect growth regulating activity of thiosemicarbazones of methyl 2‐pyridyl ketones

AbstractThirty‐six thiosemicarbazones of methyl 2‐pyridyl ketone and of some other methyl ketones were tested on Dysdercus cingulatus, Drosophila melanogaster, Locusta migratoria, Aedes aegypti, Tenebrio molitor and Musca domestica. Several derivatives were toxic, delaying or preventing ecdysis. The structure‐activity relationship is discussed. The mode of action of these compounds appears to be different from that of juvenile hormones, anti‐juvenile hormones, or chitin biosynthesis inhibitors.

The formation of cobalt(II) halide complexes containing neutral bidentate ligands

Preparation of cobalt(II) halide complexes with neutral bidentate ligands, including 2-pyridyl alkyl ketones, is reported. 2-Pyridyl alkyl ketones act as monodentate or bidentate ligands depending on the reaction solvent used. Tetrahedral complexes are isolated for all potential σ-donating neutral ligands.trans-Octahedral complexes are formed only if the neutral ligands are strong σ-donors and π-acceptors. The stereochemistry of cobalt(II) halide complexes is discussed in relation to the nature of the neutral ligands.

Nadh models-19

N-(Cyclopropylmethylene)phenylamines ( 1a-c), cyclopropyl 2-pyridyl ketones ( 5-c) and ethyl cyclopropylmethlenepyruvate ( 14) have been subjected to reduction by l,4-dihydropyridines [3,5-diethoxycarbonyl-2,6-dimethyl-l,4-dihydropyridine ( 2) and/or 1-benzyl-1,4-dihydronicotinamide (7)]in the presence of magnesium ions, and by tin hydrides. The reactions with 1,4-dihydropyridines do not involve cleavage of the three-membered ring in the reduction step. The observed acyclic product from 2-pyridyl 2,2-dimethylcyclopropyl ketone ( 5b) is a consequence of ring cleavage prior to reduction of the carbonyl function. In contrast, reduction of 1a-c and 5-c by tin hydrides leads to products in which the cylopropane moiety has undergone ring-opening. These findings support a hydride transfer mechanism for reductions with NADH models.

Studies on organometallic compounds. III. Reaction of trimethylstannylazines with acyl chlorides. A novel C-C bond formation of pyridine nuclei.

Introduction of an acyl group at the α-, β-, and γ-positions of pyridine nuclei was accomplished. 2-Trimethylstannyl-pyridine and -quinoline and 1-trimethylstannyliso-quinoline directly reacted with various acyl chlorides to give the corresponding 2-pyridyl, 2-quinolyl, and 1-isoquinolyl ketones, respectively. Reaction of 3-trimethylstannyl-pyridine, -quinoline, and -isoquinoline with acyl chlorides proceeded smoothly under catalysis by PdCl2 or PdCl2 (PPh3)2 to afford the corresponding ketones in good yields. Similarly, 4-pyridyl, -quinolyl, and -isoquinolyl ketones were prepared from the corresponding 4-trimethylstannyl derivatives and acyl chlorides.