One for Many: A Universal Reagent for Acylation Processes

Abstract

This work describes acylation reactions facilitated by at ype of heterocycle-based acyl transfer agent, 2-acyloxypyridazinone.R eactions of 2-acyloxypyridazinone with carboxylic acids yield mixed carbonic anhydride intermediates,w hich are reactive and couldb ec oupled with aw ide range of substrates including acids,a mines,a lcohols,a nd thiols.T he wide substrate scope,e ase of operation (no additive or catalyst), storage and handling stability,a nd atom-efficiency from recycling the heterocycle carrierm ake the reported acylating agent attractive for acylation-basedcoupling reactions.Keywords: 2-alkoxycarbonylpyridazin-3(2H)-ones; acylating agents;c oupling reactions;h eterocycles; mixed carbonic anhydrides Acylation is one of the most widelyu seds ynthetic processesf or functional group transformation,e .g.,t o produce amides from amines and esters from alcohols.[1] Owing to the widespread use of acylation in various areas, including pharmaceuticals, [2] synthetic polymers, [3] and functional molecular materials, [4] significante ffort has gone into developing acylating agents suitable for individual applications.[5] Although there have been advances in acylation processes, existing methods [5b] have inherentl imits in termso fs ubstrate scope,a tom-efficiency,h arsh reactionc onditions,a nd/or the necessityo fcatalysts or additives. Thedevelopment of an acylation systemwith easy operationa nd universal substrate scope remains challenging.An optimum acylation systemm ust meet at least the following criteria:( i) ab road substrate scope,i .e., an acylating agent not limited to primary amines,o ne of the most widelys tudied functional groups in acylation, but one applicable to aw ide range of functional groups including alcohols andt hiols;( ii)t he ability to operate without catalysts and/or additives;( iii)t he ability to enhance atomicefficiency by recycling of reagents;a nd (iv) ease of handling and storage under ambient conditions.H erein, we report an acylating agent based on ah eterocycle,4 ,5-dichloropyridazin-3(2H)-one (DCPN), that meets the abovefourcriteria (Figure 1). Thep yridazinone-based acylating agent facilitated coupling reactions via acylation under neutral conditions without catalysts anda dditives,a nd more interestingly,e xhibited aw ide substrate scope (amines,a lcohols,c arboxylica cids andt hiols). The coupling reactions proceeded throught he formation of an asymmetric carbonic anhydride,w hich was ar eactive intermediate,f ollowed by addition of the substrate to one of the carbonyl carbons in the anhydride.T he pyridazinone carrier, ab y-product formed upon completion of the reaction, is quantitatively isolable through extraction with basic aqueous solution (20 wt% NaOH) or, at least in part, through recrystallization after completion of the reaction. Thee ase and simplicity of isolatingt he by-product from the reaction solution maket he acyloxypyridazinonea na ttractivea cylating agent for av ariety of synthetic applications.Ac entral idea of this work was to utilize 2-acyl...

Stereoselective synthesis and characterization of monocyclic cis‐β‐lactams containing 5‐methyl‐1,3,4‐thiadiazole‐2‐thiol moiety

“…The method used for their product ptseparation is column chromatography and the product formation is necessarily temperature-dependent. An extremely specific reagent ethyl-4,5-dichloro-6-oxopyridazine-1-(6H)carboxylate is convenient for conversion of mixed esters, thioesters, amides, and carbonic anhydride from a carboxylic acid [29]. It has been reported that 2-ethoxy carbonyl DCPN are good leaving group [30], stable, atom-economic acyl sources, and non-hygroscopic [31] in the reaction by carboxylic acids [32].…”

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

“…The starting materials were prepared according to the literature procedures [ 21 , 23 , 30 – 31 ]. The known compounds, 1a , 1b [ 32 ], 1c [ 33 ], 1f–1h [ 34 ], 1i [ 35 ], 1k [ 36 ], 1l [ 31 ], 1m [ 37 ] and 1n [ 38 ] were characterized by comparison of the spectral data with those reported in the literature.…”

Use of deep eutectic solvents as catalyst: A mini-review

“…Aromatic ketones are valuable precursors for the synthesis of agrochemicals, pharmaceuticals, fragrances and also dyes. These molecules are generally synthesized by Friedel-Crafts acylation using Lewis acids as catalysts [31][32][33][34][35][36]. However, the need for the excess use of the catalyst, the unfeasible recovery process and the environmental problems have directed researchers to alternative methods.…”