Important Industrial Procedures Revisited in Flow: Very Efficient Oxidation and N-Alkylation Reactions with High Atom-Economy

Abstract

The atom economy concept is one of the earliest recognition for green and sustainable aspects of organic synthesis. Over the years, novel technologies emerged that made this important feature of reactions into practice. Continuousflow devices increased the efficiency of the chemical transformations with novel process windows (high T, high p and heterogeneous packed catalysts etc.) and increased safety which turned the attention to reexamine old, industrial processes. Oxidation can be performed under flow catalytic conditions with molecular oxygen; alcohols can be oxidized to carbonyl compounds with high atom economy (AE=87 %). Using O 2 and 1 % Au/TiO 2 , alcohol oxidation in flow was achieved with complete conversion and >90 % yield. N-alkylation is another good example for achieving high atom economy. Under flow catalytic conditions (Raney Ni), amines were successfully reacted with alcohols directly (AE=91 %) with >90 % conversion and selectivity. In both examples, the effective residence time was less than 1 min. These two examples demonstrate the significant contribution of flow technology to the realization of key principles in green and sustainable chemistry.

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

“…Former attempts with a similar flow system showed that reaction temperature below 200°C produces predominantly N-alkylated products [25]. These observations led to the conclusion that cleavage of the carbon-hydrogen bond might require higher temperature.…”

1. Catalysis in flow

“…However, there are severe flammability and explosive hazards associated with aerating organic solvents, which must be overcome before they can be implemented industrially. More recently, 1% Au/TiO 2 was utilized using the same system for the oxidation of 1-phenyl ethanol to the corresponding ketone in a single-pass mode (Table 1.3, entry 2) [69]. Taking advantage of the small reactor volume of a catalyst cartridge offered by a X-Cube reactor, aerobic oxidation of primary and secondary alcohols to aldehydes and ketones can be achieved using Ru/Al 2 O 3 as catalyst [68].…”

Flow reactors integrated with in-line monitoring using benchtop NMR spectroscopy

“…[1][2][3][4][5][6][7][8][9] Micromixing, efficient heat transfer in tubular reactors having a high surface-to-volume ratio and enhanced safety due to the small size of reactors are some of the most salient benefits of continuous flow chemistry compared to traditional batch processes. [10][11][12][13] As a result, flow approaches in synthetic chemistry rapidly thrives in academic and industrial laboratories [14][15][16][17][18] and affords considerable opportunities to develop novel transformations and access new reactivities under unusual experimental conditions. [19][20][21][22][23][24] Both, deep mechanistic understanding and optimization of complex synthetic transformations conducted either in flow or in batch modes, require the use of suitable analytical technologies.…”