Syntheses of Isoquinoline and Substituted Quinolines in Charged Microdroplets

Abstract

A Pomeranz-Fritsch synthesis of isoquinoline and Friedländer and Combes syntheses of substituted quinolines were conducted in charged microdroplets produced by an electrospray process at ambient temperature and atmospheric pressure. In the bulk phase, all of these reactions are known to take a long time ranging from several minutes to a few days and to require very high acid concentrations. In sharp contrast, the present report provides clear evidence that all of these reactions occur on the millisecond timescale in the charged microdroplets without the addition of any external acid. Decreasing the droplet size and increasing the charge of the droplet both strongly contribute to reaction rate acceleration, suggesting that the reaction occurs in a confined environment on the charged surface of the droplet.

A Study of Heterogeneous Catalysis by Nanoparticle‐Embedded Paper‐Spray Ionization Mass Spectrometry

“…Fort he above three reactions (Figures 2, 3, and 4), we performed control studies with normal filter paper without the embedded nanocatalysts.N one of the control studies (data not shown) was able to catalyze any of the above reactions in the absence of catalytic nanoparticles.W ea lso performed av oltage-dependent study of those reaction (Figures 2, 3, and 4). On changing the paper spray voltages from 0t oÀ7kV, the reaction efficiencies (formation of intermediates and products) increased (Supporting Information, Figures S15 and S16), which indicates the requirement of abasic environment for these reactions,which is provided by the abundant solvent (water) reduction at elevated negative voltages.Itshould be noted that the increased negative spray voltage can also improve the ionization efficiencya nd ion detection sensitivity in mass spectrometry,w hich can also contribute to modifying the product-to-reactant ratios [20] (Supporting Information, Figures S15 and S16). We also investigated the addition of base to the reaction mixture (pH % 11) but found no increase in the reaction yield.…”

Reaction Acceleration in Thin Films with Continuous Product Deposition for Organic Synthesis

“…[1] Confined volumes can take the form of sprays,g enerated by nebulization using electric and/ or magnetic fields,o rt hin films,g enerated for example by drop casting.F or instance,the Hantzsch reaction proceeds in 90 %y ield in charged microdroplets generated by electrospray. [5] Many other reactions involving C À H, [6] C À C, [2][3][4][5]7] C À N, [2,8] and CÀO [9] bond formation have been reported to be accelerated by factors of 10-10 6 in confined volumes. [5] Many other reactions involving C À H, [6] C À C, [2][3][4][5]7] C À N, [2,8] and CÀO [9] bond formation have been reported to be accelerated by factors of 10-10 6 in confined volumes.…”

“…[2] Base-catalyzed Claisen-Schmidt condensation is accelerated in electrosprayed droplets, [3] in levitated Leidenfrost droplets, [4] and in the paper spray experiment that combines athin film format with charged droplet emission. [5] Many other reactions involving C À H, [6] C À C, [2][3][4][5]7] C À N, [2,8] and CÀO [9] bond formation have been reported to be accelerated by factors of 10-10 6 in confined volumes. [10] The underlying reasons for acceleration are increased reagent reactivity,d ue to partial desolvation at the interface, [11] pH value change, [12] and increased reagent concentration associated with solvent evaporation.…”

Chemoselective N‐Alkylation of Indoles in Aqueous Microdroplets

“…It has become apparent that the environment in microdroplets is strikingly different from that of the corresponding bulk phase . Many features of microdroplets may contribute to reaction acceleration, such as the confinement of reagents in small‐volume reactors, the large surface‐to‐volume ratios of small reactors, the higher density of molecules on the surface of the microdroplets, solvent evaporation with associated increases in reagent concentrations, and extreme pH values . Thus far, most of the reported accelerated reactions in microdroplets mirror the products found in the bulk reaction .…”