Continuous Flow Liquid–Liquid Separation Using a Computer-Vision Control System: The Bromination of Enaminones with N-Bromosuccinimide

Dedicated to Professor Steven V. Ley, mentor and friend, on the occasion of his 70^th birthday

Abstract

Incorporating open-source software components (Python, OpenCV), a computer-vision system was used to control the interface level in a gravity-based inline liquid–liquid separation device. This was used in the continuous flow bromination of a series of enaminone substrates. The main byproduct of the reaction, succinimide, was efficiently extracted into the aqueous stream, providing clean products without the need for further purification.

Key words

continous flow - liquid–liquid separation - bromination - enaminone - open source - computer-vision - OpenCV - Python

• References and Notes

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• 16 Representative Procedure for the Formation of the Enaminones (3i) Cyclohexanedione (1.55 g, 13.8 mmol, 1 equiv) and 4-chlorobenzylamine (1.8 mL, 14.8 mmol, 1.1 equiv) were added to a flask under nitrogen. To this was added toluene (50 mL) and EtOH (2.5 mL), and the mixture was stirred at reflux for 3 h. Upon completion the solvent was removed under reduced pressure, forming a yellow-brown solid, which was recrystallised from toluene. The product was made up of yellow-brown crystals; yield 71% (2.31 g); mp 166.8–168.4 °C (lit.: 170–172 °C). ¹H NMR (300 MHz, CDCl₃): δ = 7.32–7.26 (2 H, m), 7.18 (J = 8.54 Hz, 2 H, m), 5.34 (1 H, br s), 5.07 (1 H, s), 4.18 (J = 5.36 Hz, 2 H, d), 2.38 (J = 6.15 Hz, 2 H, t), 2.27 (J = 6.53 Hz, 2 H, t), 1.99–1.91 (2 H, m, H-2). ¹³C NMR (100 MHz, CDCl₃): δ = 197.4, 165.2, 135.3, 133.6, 128.9, 97.5, 46.3, 36.4, 29.5, 21.9. IR: ν = 3247 (NH), 3049, 1538 (C=O), 683 cm^–1. Representative Procedure for the Continuous Flow Bromination (4i) Using the apparatus shown in Figure 3, the system was primed with CH₂Cl₂ and the aqueous extraction solvent for several minutes until there were no air gaps in the flow path. 3-[(4-chlorobenzyl)amino]cyclohex-2-enone (3i, 0.100 M in CH₂Cl₂) was loaded in to the 3 mL injection loop. NBS (0.106 M in CH₂Cl₂) was loaded into the 4.1 mL injection loop. The NBS loop was injected into the system 20 s prior to the substrate loop. Organic solution exiting the system was collected for 20 min. The solvent was removed under reduced pressure to afford a yellow-brown solid; yield 93% (87.5 mg): mp 121.5–122.3 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.32 (J = 7.43 Hz, 2 H, d), 7.18 (J = 7.65 Hz, 2 H, d), 6.12 (1 H, br s), 4.49 (J = 5.17 Hz, 2 H, d), 2.51 (J = 6.34 Hz, 2 H, t), 2.45 (J = 6.03 Hz, 2 H, t), 1.98–1.84 (2 H, m). ¹³C NMR (100 MHz, CDCl₃): δ = 187.8, 161.0, 136.0, 133.7, 129.2, 128.0, 96.6, 46.5, 36.6, 26.7, 20.7. IR: ν = 3260 (NH), 2988, 2955, 2939, 2901, 2884, 1584 (C=O), 800, 715 cm^–1.