Chip-Based On-Line Nanospray MS Method Enabling Study of the Kinetics of Isocyanate Derivatization Reactions

Abstract

The reaction of propyl isocyanate (2), benzyl isocyanate (3), and toluene-2,4-diisocyanate (4) with 4-nitro-7-piperazino-2,1,3-benzoxadiazole (1) to yield the corresponding urea derivatives 5 was carried out in a continuous flow glass microfluidics chip. Real-time monitoring of the derivatization reactions was done by electrospray ionization mass spectrometry, making use of a recently reported modular chip-MS interface. Rate constants of 1.5 x 10(4), 5.2 x 10(4), and 2.4 x 10(4) M(-1) min(-1) were determined for 2, 3, and 4, respectively. Using macroscale batch conditions, the rate constants are 3-4 times lower. The faster on-chip kinetics is attributed to the more efficient molecular diffusion in the micrometer-sized channel.

Online Monitoring of Polymerizations: Current Status

“…[60] In those cases, a six-port switching valve with a sample loop, a mass rate attenuator, or other automated sampling methods were applied for sample transfer from the reactor outlet into the mass spectrometer. [61][62][63] The first continuous online mass spectrometric coupling was performed by Heitbaum and coworkers. [64] Here an electrochemical cell was coupled with a mass spectrometer to monitor the electrooxidation of N,N-dimethylaniline, where electrochemically generated products can be directly monitored form solution and potential-dependent formation of dimers and trimers is shown.…”

Continuous flow reaction monitoring using an on‐line miniature mass spectrometer

“…There has been considerable interest in the in-line coupling of microchip reactors to mass spectrometers. [45][46][47][48][49][50][51] In some examples, a nanospray emitter has been fabricated as part of the microchip whereas, in others, a direct fluidic coupling has been made between the microchip and a standard ESI source.…”

A microfluidic reactor for rapid, low‐pressure proteolysis with on‐chip electrospray ionization

“…The benefits of coupling microfluidic sample handling with the analytical power of mass spectrometry prompted the development of the first electrospray‐coupled microfluidic device (ECMD) in 1997 28. Since then, ECMDs have been introduced for a wide range of applications,29 from enhancement of ESI10, 30, 31 to millisecond time‐resolved solution‐phase kinetics 32–34. The most common applications are in proteomics, where microfluidics is seen as a promising solution to the experimental challenges of separation,18–20 protein digestion12, 26 and high throughput8, 35 with small volume samples.…”