Efficient and Mild Protocol for the Synthesis of 4(3)‐Substituted 3(4)‐Nitro‐1H‐pyrroles and 3‐Substituted 4‐Methyl‐2‐tosyl‐1H‐pyrroles from Nitroolefins and Tosylmethyl Isocyanide in Ionic Liquids

Abstract

A mild and convenient method for the synthesis of 4(3)-substituted 3(4)-nitro-1H-pyrroles and 3-substituted 4-methyl-2-tosyl-1H-pyrroles from nitroolefins and tosylmethyl isocyanide (TosMIC) in ionic liquid 1-butyl-3-methylimidazolium bromide ([bmIm]Br) was developed. The reactions were performed at room temperature with KOH as base with good yields in a short time (about 2 h). Some tough conditions, such as absolutely anhydrous organic solvents, low temperature, hazardous and expensive strong base or organic base, were not needed. The yields of 4(3)-substituted 3(4)-nitro-1H-pyrroles were moderate, but excellent yields were achieved for the preparation of 3-substituted 4-methyl-2-tosyl-1H-pyrroles. This strategy was quite general and it worked in a broad range of nitroolefins with aromatic, aliphatic or heterocyclic substituents. The recovered ionic liquid could be reused as solvent for several times without significant decrease of reaction yields.

Pyrrole: a resourceful small molecule in key medicinal hetero-aromatics

“…28 Qin et al proposed a mild and convenient method for the synthesis of 4(3)-substituted 3-(4)nitropyrrole 30 from nitro olens and TosMIC in ionic liquid 1-butyl-3-methylimidazolium bromide ([bmIm] Br). 29 Borbas et al found that bacteriochlorins gets absorbed strongly in the near infrared region and hence are suited for diverse photo medical application. A de novo route was exploited to prepare synthetic bacteriochlorins 31 using TosMIC chemistry (Scheme 6).…”

Synthesis of Multi-Substituted Pyrrole Derivatives Through [3+2] Cycloaddition with Tosylmethyl Isocyanides (TosMICs) and Electron-Deficient Compounds

“…As shown in Scheme 3 , the electron-withdrawing groups may be esters, amides, ketones, nitros, cyanos, aryls, etc. [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Based on the different types of electron-withdrawing group attached to the alkenes, they are classified and described in order ( Scheme 3 ).…”

“…In 2009, Xiaoqi Yu and co-workers reported that 4(3)-substituted 3(4)-nitro-1 H -pyrrole 111 can be synthesized from nitroene 110 and TosMIC 16 in the presence of the ionic liquid 1-butyl-3-methylimidazolium bromide ([bmIm]Br). This reaction can be widely applied to aromatic, aliphatic or heterocyclic substituted nitroolefins, and the recovered ionic liquid can be repeatedly used as a solvent without significantly reducing the yield ( Scheme 33 ) [ 52 ].…”