Bu₄NHSO₄‐Catalyzed Direct N‐Allylation of Pyrazole and its Derivatives with Allylic Alcohols in Water: A Metal‐Free, Recyclable and Sustainable System

Abstract

Allylic amines are valuable and functional building blocks. Direct N-allylation of pyrazole and its derivatives as an atom economic strategy to provide allylic amines has been achieved only using commercial Bu 4 NHSO 4 as the metal-free catalyst and water as the solvent without any additives. 11-93% isolated yields were obtained for the N-allylation of pyrazole and its derivatives with allylic alcohols. Bu 4 NHSO 4 could be reused for six times by simple extraction nearly without loss of catalytic activity and was also suitable for a gram-scale production. The reaction of allylic ether and pyrazole did not occur to give the desired product indicated that allylic ether was not the active intermediate in the pathway. Density functional theory (DFT) calculations reveal that there are hydrogen bonding effects among substrates, solvent and catalyst, especially the one formed between allylic alcohol and H 2 O. Control experiments in different protic solvents further demonstrate the intermolecular hydrogen bonding of allylic alcohol and water.

DES‐Type Interactions To Promote Solvent‐Free and Metal‐Free Reactions between Nitrogen‐Containing Heterocycles and Allylic Alcohols

“…1 : 1 isomers mixture), [49,50] but it seems to influence in the environment in which the substitution occurs. [50,51] The presence of bcmimCl without any solvent may facilitate the proton (HÀ N) abstraction promoting the nucleophilic addition of pyrazole to the incipient allylic carbocation, wherein steric constraints imposed by the substituent is the factor favoring the regioselectivity to 19 a. This is in concordance with the fact that 3,5-dimethylpyrazole needed a longer reaction time (6 h) to quantitatively yield compound 20 (Scheme 4).…”

“…The methyl substituent in 3(5)‐position does not have a great influence on the tautomer equilibrium of the starting 3(5)‐methylpyrazole (ca. 1 : 1 isomers mixture), [49,50] but it seems to influence in the environment in which the substitution occurs [50,51] . The presence of bcmimCl without any solvent may facilitate the proton (H−N) abstraction promoting the nucleophilic addition of pyrazole to the incipient allylic carbocation, wherein steric constraints imposed by the substituent is the factor favoring the regioselectivity to 19 a .…”

‘In-water’, nickel-catalyzed mild preparation of allylic amines employing alcohols: application to ‘all-water’ synthesis of pharmaceuticals

“…11 To the best of our knowledge, all known catalytic nickel N -allylations were performed in organic medium with or without additives (co-catalyst, n Bu 4 NOAc, and molecular sieves), appealing another opportunity to discover an additive-free ‘in-water’ N -allylation process employing alcohols under mild conditions. 11,12…”

Dehydrative Cross-Coupling for C–N Bond Construction under Transition-Metal-Free Conditions

“…For instance, the amazing intramolecular versions developed by Hirai, − Hegedus, et al have a broad range of applications in preparing bioactive compounds and natural products. ,, On the other hand, elegant catalysts including montmorillonite, Al, Fe, and strong Bronsted acids were also well developed, mainly targeting tert - and sec -allylic alcohols. In the case of 1,3-diphenyl-2-propen-1-ol, promising Bu 4 NHSO 4 and functionalized imidazolium chloride were identified as recyclable and sustainable catalytic systems for C–N bond construction by Miao and Pastor, respectively. Since Shibasaki’s pioneering investigation concerning Bi catalyst in 2007, there are very few examples on the use of primary allylic alcohols in C–OH/N–H cross-coupling under transition-metal-free conditions.…”