ONSH: Optimization of Oxidative Alkylamination Reactions through Study of the Reaction Mechanism

Abstract

Oxidative alkylamination of electron-deficient (hetero)aromatic compounds, via the nucleophilic substitution of hydrogen, is a methodology that has made significant progress since the introduction of AgPy(2)MnO(4) as oxidant. This oxidant generally gives good conversions and yields, whereas the use of KMnO(4) only sometimes works equally well. In order to rationalize this, the reaction mechanism of oxidative alkylamination has been studied. 3-Nitropyridine (1), 1,3-dinitrobenzene (2), and quinazoline (3) were chosen as model substrates and n-butylamine and pyrrolidine as model alkylamines. The rate-limiting step of the mechanism for these substrate/alkylamine combinations was determined. With the use of (1)H NMR spectroscopy thermodynamic properties of sigma(Eta)-adduct formation were deduced and the effect of additives on the adduct formation was investigated. The fundamental insights resulting from these studies led to the identification of a cheap additive (tetrabutylammonium chloride), which in combination with the standard and cheap oxidant KMnO(4) generally gave excellent yields, similar to the ones previously obtained with more expensive AgPy(2)MnO(4).

Solvent-Free or Low-Solvent Large-Scale Preparation of Chloropyrimidine and Analogues

“…118–120 °C); MS (EI, m / e ) 197.9 (100), 199.9 (64). Spectroscopic data matched literature reported data: 1 H NMR …”

“…Spectroscopic data matched literature reported data: 1 H NMR. 33 2,4-Dichloropyrido [3,2-d] ' ASSOCIATED CONTENT b S Supporting Information. NMR spectra of new compounds or known compounds with no previous report of spectra.…”

Direct Introduction of Sulfonamide Groups into Quinoxalin‐2(1H)‐ones by Cu‐Catalyzed C3‐H Functionalization

“…Initially, the Cu(I) catalyst A reacts with peroxydisulfate B to produce active Cu(II) species C , SO 4 2− and SO 4 .− radical anion ( D ), and D abstracts a hydrogen atom from sulfonamide 2 a to generate HSO 4 − and the corresponding sulfonamide radical F . Subsequently, the coordination of C with the nitrogen atom of the C=N bond in the quinoxalin‐2(1 H )‐one substrate leads to the polarization of the C=N double bond and gives the active species E , which undergoes an addition with the sulfonamide radical F to provide the key intermediate G . Finally, the intermediate G goes through a single‐electron transfer and deprotonation in succession to afford the target product 3 a , with regenerating the copper(I) catalyst A to complete the catalytic cycle.…”

Reactivity of Ortho-Palladated Benzamides toward CO, Isocyanides, and Alkynes. Synthesis of Functionalized Isoindolin-1-ones and 4,5-Disubstituted Benzo[c]azepine-1,3-diones

“…The 1 H NMR data are in agreement with those reported in the literature. 40 Synthesis of 2-Methylisoindoline-1,3-dione (N-Methylphthalimide) (4b). A solution of 2b (139 mg, 0.27 mmol) in acetone (15 mL) was stirred under a CO atmosphere (1.4 bar) for 3 h. A black precipitate of Pd gradually formed.…”