Indium(III)-catalyzed synthesis of N-substituted pyrroles under solvent-free conditions

Abstract

Vários pirróis N-substituídos foram sintetizados pela reação de -dicetonas (R 1 C(O) CH 2 CH 2 C(O)R 2 : R 1 , R 2 = Me, Ph) com aminas (RNH 2 : R = Alkyl, Aryl, TsNH) ou diaminas (1,6-diaminohexano and 1,2-diaminoetano) na presença de tribrometo de índio, tricloreto de índio ou trifluorometanossulfonato de índio a temperatura ambiente e sem solventes. O protocolo envolve operações simples e os produtos são isolados em excelentes rendimentos (81-98%).A variety of N-substituted pyrroles have been synthesized by reacting -diketones (R 1 C(O) CH 2 CH 2 C(O)R 2 : R 1 , R 2 = Me, Ph) with amines (RNH 2 : R=Alkyl, Aryl, TsNH) or diamines (1,6-diaminohexane and 1,2-diaminoethane) in the presence of indium tribromide, indium trichloride or indium trifluoromethanesulfonate at room temperature under solvent-free conditions. The experiment protocol features simple operations, and the products are isolated in high to excellent yields (81-98%). Keywords: indium tribromide, indium trichloride, indium trifluoromethanesulfonate, pyrroles, solvent-free conditions IntroductionHeterocyclic small molecules play an important role in the search for new therapeutic and drug candidates. 1Pyrroles are an important class of heterocyclic compounds and are structural units found in a vast array of natural products, synthetic materials, and bioactive molecules, such as heme, vitamin B12, and cytochromes.2 Pyrroles also play crucial roles in nonlinear optical materials as well as in supramolecular chemistry.3 Therefore, the enormous number of procedures have been developed for the construction of pyrroles. Classical methods for their preparation include the Knorr, 4 Hantzsch, 5 and PaalKnorr condensation reactions. [6][7][8][9][10][11][12][13][14][15][16] Among these methods, the most commonly used and straightforward approach for the preparation of pyrroles is the direct condensation of -diketones and amines (Paal-Knorr reaction) in the presence of protonic acids such as AcOH, 6 p-TsOH. In continuation of our interest in Lewis acid-catalyzed and green chemistry organic reactions, 23 we herein wish to report a simple, practical and efficient method for the synthesis of pyrroles from -diketones and amines using indium(III) salt as catalyst at room temperature under solvent-free conditions (Scheme 1). Results and DiscussionInitially, the efficacy of various catalysts was tested in the model reaction under solvent-free condition at room temperature (Table 1). The results showed that InCl 3 , InBr 3 and In(OTf) 3 were superior to other Lewis acids with respect to reaction times and product yields. Entry 1 showed the blank reaction without addition of any catalyst, in this case only 29% 2,5-dimethyl-1-phenyl-1H-pyrrole (3a) was obtained after 24 h. For the sake of comparison, the reaction was carried out using other anhydrous chloride, such as ZnCl 2 , NiCl 2 , SrCl 2 and CuCl 2 under solvent free conditions (Entries 2-8). However, these chlorides showed lower activity than InCl 3 under same reaction conditions. We examined influence of solvents ...

One‐pot synthesis of N‐substituted pyrroles catalyzed by polystyrene‐supported aluminum chloride as a reusable heterogeneous lewis acid catalyst

“…However, based on the experimental results and by referring to the literature [8,27,28], the mechanism of the pyrrole formation proceeds by the usual pathway proposed using Lewis acids. Table 3 compares efficiency of PS/AlCl 3 (time, yield, reaction conditions) with efficiency of other Lewis acid catalysts in synthesis of 3a obtained by other groups.…”

Catalytic activity of the nanoporous MCM-41 surface for the Paal–Knorr pyrrole cyclocondensation

“…Numerous catalysts and protocols have already been implemented to synthesize 2,5-disubstituted pyrroles, e.g., Lewis acids [10][11][12][13][14], heterogeneous solids having active acidic sites [15][16][17][18][19][20][21], ionic liquids [22,23], deep eutectic solvents [24], an enzyme [25], and organocatalysts [26,27]. Nevertheless, from the standpoint of synthesis, some of these procedures have restricted activity and suffer from operational and practical problems; they are costly to prepare and time consuming (causing high labor time).…”

Polystyrene-supported GaCl3 as a highly efficient and recyclable heterogeneous Lewis acid catalyst for one-pot synthesis of N-substituted pyrroles

“…Despite these new developments, the PaaleKnorr reaction remains one of the most significant and simple methods which consists the cyclocondensation of primary amines with 1,4-dicarbonyl compounds to produce N-substituted pyrroles. Several catalysts have been used to promote this reaction including HCl [11], p-TSA [12], H 2 SO 4 [13], Sc(OTf) 3 [14], Bi(NO 3 ) 3 $5H 2 O [15], SnCl 2 $2H 2 O [16], Ti(OPr i ) 4 [17], RuCl 3 [18], InCl 3 , InBr 3 , In(OTf) 3 [19], zeolite [20], Al 2 O 3 [21], montmorillonite K10 [22], silica sulfuric acid [23], layered zirconium phosphate and phosphonate [24], Fe 3þ -montmorillonite [25], montmorillonite KSF-clay and I 2 [26]. Additionally, the above cyclocondensation process could proceed in ionic liquid [27] or ultrasonic and microwave irradiation [28].…”