Molecularly Imprinted Polymer as an Eco-Compatible Nanoreactor in Multicomponent Reactions: A Remarkable Synergy for Expedient Access to Highly Substituted Imidazoles Ahmad Shaabani,* Ronak Afshari, Seyyed Emad Hooshmand, and Mina Keramati Nejad Faculty of Chemistry, Shahid Beheshti University, Daneshjou Boulevard, Tehran 19396-4716, Iran * S Supporting Information ABSTRACT: In this paper, an eco-compatible molecularly imprinted polymer (MIP) nanoreactor synthesized via miniemulsion polymerization was designed, and its catalytic activity was investigated in multicomponent reaction trans- formations for the first time. The synthesized MIP nanoreactor was characterized by means of Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, transmission electron micros- copy, and dynamic light scattering. The imidazole template- derived sites created within a polymeric matrix allow MIP nanoreactors to directly catalyze the reaction and conduct the target molecule. The results show the applicability of MIP nanoreactors in a one-pot expeditious synthesis of tri- and tetrasubstituted imidazole derivatives via pseudo-four- and four- component reactions with excellent yields and purities. In addition, biocompatibility and cytotoxicity of MIP nanoparticles were examined, and no obvious adverse effects on the viability of human fibroblast cells were observed. This green and facile catalytic route has an easy setup, and the products are easily isolated without tedious purification such as aqueous workup or chromatography in high purity. Meanwhile, MIP nanoreactors showed admirable potential in reusable catalysis, being recycled for several runs without losing significant activities.The MIP nanoreactor utilization strategy can be extended to the other multicomponent reactions leading to manifold pharmaceutical and environmental applications. KEYWORDS: Molecularly imprinted polymer, Nanoreactor, Heterogeneous catalyst, Multicomponent reaction, Imidazole, Heterocyclic chemistry ■ INTRODUCTION Nature, with no doubt, is the best creator, which inspires us to create the symphony of high performance biomimetic artificial constructions that are meant to overcome many human obstacles. One of these obstacles is irrecoverable “time”. Humans have always believed that time is a valuable factor in each activity, as the famous proverb says "time is money". Accordingly, an attitude to saving time has been the driving force for many inventions throughout the history of science. 1 In this sense, in chemistry, the development of efficient catalysts for reducing the time of the principal reactions has been a hot field for the synthesis of organic and medicinal compounds in recent years. 2 Besides conventional catalysts such as Lewis or Brønsted acids or bases, nowadays, nanocatalysts such as supported catalysts, 3 metal organic frameworks 4 or zeolite, 5 ionic liquids, 6 and polymer-based catalysts 7 as well as enzymes 8 have been used as a new class of catalysts for many of the organic and inorganic transformations. In the new generation of catalysts, besides basic and acidic functional groups, other factors play a key role for catalytic activity, such as hole theory or cavity effects, surface contact increase, deep hydrogen bonding, etc. 9-11 Molecular imprinting technology (MIT) is a considerable technique for polymer networks synthesis with highly specific memorized cavities for a given compound, and the retention mechanism involved is based on molecular recognition. 12-14 The elegance of molecular imprinting and recognition is reminiscent of psychological phenomena in nature, spurring many organic scientists to mimic it as enzyme-mimetic catalytic systems. 15 In the procedure, the target organic structure acts as the template, and then the monomers and cross-linker are arranged (covalently or noncovalently) around the template and polymerized to form a cast-like shell. After the polymer- ization process, the template is removed, and a snapshot of the network is taken so that the resultant molecular assembly specifically binds this template, and cavities are complementary with the shape and the functional group positions of the template. Subsequently, a molecular memory with the ability to rebinding with the template with high selectivity is created in the polymer matrixes. 16-18 Similar to antibody catalysts, these Received: August 9, 2017 Revised: August 20, 2017 Published: September 4, 2017 Research Article pubs.acs.org/journal/ascecg © 2017 American Chemical Society 9506 DOI: 10.1021/acssuschemeng.7b02741 ACS Sustainable Chem. Eng. 2017, 5, 9506-9516