A Hantzsch synthesis of 2-aminothiazoles performed in a heated microreactor system

Abstract

This paper presents the first example known to the authors of a heated organic reaction performed on a glass microreactor under electro-osmotic flow control. The experiments consisted of the preparation of a series of 2-aminothiazoles by means of a Hantzsch reaction of ring-substituted 2-bromoacetophenones and 1-substituted-2-thioureas carried out in microchannels, with the aim of investigating the generic utility of the reactor in carrying out analogue reactions. The reactions were performed on T-design microchips etched into a thin borosilicate glass plate and sealed over with a thick borosilicate top plate containing reservoirs. The mobility of the reagents and products was achieved using electro-osmotic flow (EOF), with the driving voltages being generated by a computer-controlled power supply. During the experiments the T-shaped chip was heated at 70 C using a Peltier heater, aligned with the channels and the heat generated by this device was applied to the lower plate. The degree of conversion was quantified by LC-MS using UV detection by comparison with standard calibration curves for starting materials and final products. In all cases, conversions were found to be similar or greater than those found for equivalent macro scale batch syntheses, thus illustrating the potential of this heated microreactor system to generate a series of compounds which contain biologically active molecules.

Parallel combinatorial chemical synthesis using single-layer poly(dimethylsiloxane) microfluidic devices

“…For instance, it would be possible to run the entire combinatorial series of reactions reported by Garcia-Egido et al in 210 s using one of the scaled up single-layer chips proposed above compared to the 4410 s needed using the sequential chip of Garcia-Egido et al, reducing the total time required to perform the reactions by a factor of 21. 4 The performance of our device compared favorably with that of the chip developed by Kikutani et al;7 using the chip, we succeeded in producing pure products at a throughput comparable to that achieved using the multilayer glass device. However, our device exhibits the additional major advantage of fabrication simplicity compared to that of Kikutani et al…”

“…For example, past achievements include the combinatorial preparation of six 2-aminothiazoles using a Hantzsch synthesis in a heated glass microreactor and the synthesis of a 7 ϫ 3 library of pyrazoles using a Knorr reaction of 1,3-dicarbonyl compounds with hydrazines. 4 In each of these studies, the reactions were run in a sequential ͑time-encoded͒ fashion by performing the component reactions sequentially in a single glass microfluidic channel. Although effective, such a procedure does not allow for synthesizing all of the compounds simultaneously, reducing the throughput of the combinatorial synthesis.…”

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…[166] Such MF reactors have played a significant role in improving the reaction conditions and production of chemicals. [167] In contrast with conventional batch systems, the use of MF to study and optimize the fabrication of a wide range of nanoparticles is attracting more and more attention [167] and their use for chemical synthesis gained a quick development with notable contributions from researchers at GlaxoSmithKline (UK), [168] Massachusetts Institute of Technology (USA), [169] the Institut für Mikrotechnik Mainz (Germany) [170] and Imperial College London (UK). [171] Since the first use of MF to prepare Cd nanoparticles on a lab-on-a-chip device, [172] advancement in the area of chemical synthesis of nanomaterials has been accelerated over the past decade.…”

Design and additive manufacture for flow chemistry

“…Although the first reports of microfluidic systems date back to the 1940's, 23 the origins of mainstream microfluidics began in the 1990s. 24 This led to a considerable drive in the field of microfluidic technology, with notable contributions from GlaxoSmithKline, 25 Massachusetts Institute of Technology, 26 and University College London. 27 Consequently, over recent years, microreaction technology has become one of the most rapidly developing research fields in synthetic and process chemistry.…”