Ping
He
a,
Paul
Watts
a,
Frank
Marken
b and
Stephen J.
Haswell
*a
aDepartment of Chemistry, University of Hull, Hull, UK HU6 7RX
bDepartment of Chemistry, University of Bath, Bath, UK BA2 7AY. E-mail: s.j.haswell@hull.ac.uk
First published on 30th October 2006
The electro-reductive coupling of activated olefins and benzyl bromide derivatives has been selected to compare the performance of single and multiple channel (scaled-out) micro-gap electrochemical flow reactors. Two working electrode configurations were evaluated; in the first a single set of electrodes was used in conjunction with a multiple flow manifold to give two and four separate flow channels; in the second independent electrodes were used within the same flow manifold. Problems with shunt currents and Joule heating in the first configuration meant that only the second configuration was reliable, giving results comparable to those obtained for the single flow cell. Excellent yields of the coupling products such as 2-benzyl-succinic acid dimethyl ester and derivatives were obtained. This demonstrates micro reactor scale-out for unsupported electrosyntheses.
In this note, the electro-reductive coupling of activated olefins and benzyl bromide derivatives has been selected to compare the performance of single and multiple channel micro-gap flow reactors.3
Fig. 1 Schematic representation of scale out of micro-gap flow cell showing (a) a single pair of electrodes and (b) independent electrode configuration for a multiple double flow system. The arrows show reagent flow direction. |
Fig. 2 Schematic representation of the C–C coupling reaction during micro reactor electrosynthesis. A flow of reagents through a rectangular duct with working and counter electrode facing each other results in the formation of products. |
Resistance measurements (80 mA, 6430A Precision component analyzer, Wayne Kerr) for independent sets of electrodes were performed and indicate that each cell has resistance of typically 1.5 kΩ (for DMF/5 mM benzylbromide/5 mM dimethylfumarate) and the total resistance for 2 and 4 parallel connections is 750 Ω and 375 Ω, respectively. The total resistance for ten cells in parallel connection would be 150 Ω, compared to 170 Ω total resistance for ten cells in series connection reported for a similar system.2a However, resistance effects under no electrolyte conditions are complicated and the current distribution within individual cells may have effects on the local resistance.
Entry | Olefin | R2–Br | Cell | Flow/ µl min−1 | Yield (R1–R2) (%)b |
---|---|---|---|---|---|
R1 | R2 | ||||
a Olefin is 5 mM, halide is 5 mM, solvent is DMF, electrode gap is 160 µm, voltage is 4–4.4 V to maintain constant current of 0.6 mA. b Yield was determined using GC based on the quantity of the product after reaction using n-decane as an internal standard. Side products include dimerization of olefin and debromination of benzyl bromides, no dimerization of benzyl bromides is detected. | |||||
1 | Dimethylfumarate | Benzyl | Single | 10 | 98 |
2 | Dimethylfumarate | 4-Methoxybenzyl | Single | 10 | 94 |
3 | Dimethylfumarate | 4-Methylbenzyl | Single | 10 | 94 |
4 | Dimethylfumarate | 4-Bromobenzyl | Single | 10 | 99 |
5 | Dimethylfumarate | 1-Phenylethyl | Single | 10 | 98 |
In order to further explore the reactant flow within the micro reactor, we estimate the average residence time and the approximate inter-diffusion time for reactants travelling between the two electrodes. At a flow rate of 10 µl min−1, the residence time and the average linear velocity are about 43 s and 0.35 mm s−1, respectively. Using the Einstein–Smoluchowski equation6 (; ddiff = distance travelled by diffusion, D = diffusion coefficient, t = time) the diffusion time across the electrode gap is estimated as typically 12–13 s. This suggests that inter-diffusion is possible. High conversion is probably due to effective inter-diffusion of the dimethylfumarate radical anion and benzyl bromide, and reactive electron transfer between the dimethylfumarate radical anion and benzyl bromide.4a
To further evaluate the scale out methodology, the same coupling reactions were conducted using double and quadruple micro-gap flow cells (see Fig. 1). The individual flow rates for each of the quadruple cells were measured and found to vary by less than 5% compared to each other and the single channel device. The cells were operated in two distinct configurations as described in the experimental section. It is important to stress that the two and four parallel flow cells used allowed the geometry, flow rate, and applied potentials of the previously optimised single flow cell to be maintained. Using the double and quadruple micro-gap flow cells the coupling reactions were carried out using both electrode configurations and the results are summarised in Table 2. Comparison with Table 1 indicates that the double and quadruple flow cells show the same level of product yield as that obtained with the single cell under the same conditions. However, volumetric flow rates equivalent to 20 µl min−1 (i.e. 10 µl min−1 × 2 flow cells) and 40 µl min−1 (i.e. 10 µl min−1 × 4 flow cells) could be achieved. This demonstrates that scale-out can be achieved without loss of performance compared to that obtained for a single cell. The performance however of the quadruple flow cell configured with only one set of electrodes was poor (configuration 1, Entry 16 in Table 2). This is due presumably to shunt currents (localised resistance changes) and a pronounced Joule heating effect.2d These problems lead to the generation of bubbles and disruption to the flow. No such problems were observed in the second configuration with electrode current individually controlled.
Entry | Olefin | R2–Br | Cellb | Electrode/reactor numberc | Flow/d µl min−1 | Product (R1–R2) yield (%) | |||
---|---|---|---|---|---|---|---|---|---|
R1 | R2 | Cell-1 | Cell-2 | Cell-3 | Cell-4 | ||||
a Olefin is 5 mM, halide is 5 mM, solvent is DMF, electrode gap is 160 µm. For the double cell (D) experiments, voltage was 3.5–4 V to maintain constant current of 0.6 mA. For multiple cell experiments (M), each cell has similar voltage value to the single cell in order to maintain a constant current of 0.6 mA. b When using the double cell geometry, a single electrode was divided into two single flow cells. In multiple cell geometry, two and four independent electrodes were used for generating 2 (M2) and 4 (M4) parallel flow cells. c The values present the number of electrode and reactor used in the cell configuration. d The flow value represents the total flow rate. e The quadruple flow cell with a single electrode (configuration 1). | |||||||||
1 | Dimethylfumarate | Benzyl | D | 1/2 | 20 | 98 | 97 | — | — |
2 | Dimethylfumarate | 4-Methoxybenzyl | D | 1/2 | 20 | 93 | 94 | — | — |
3 | Dimethylfumarate | 4-Methylbenzyl | D | 1/2 | 20 | 93 | 94 | — | — |
4 | Dimethylfumarate | 4-Bromobenzyl | D | 1/2 | 20 | 99 | 99 | — | — |
5 | Dimethylfumarate | 1-Phenylethyl | D | 1/2 | 20 | 98 | 97 | — | — |
6 | Dimethylfumarate | Benzyl | M2 | 2/2 | 20 | 98 | 98 | — | — |
7 | Dimethylfumarate | 4-Methoxybenzyl | M2 | 2/2 | 20 | 94 | 94 | — | — |
8 | Dimethylfumarate | 4-Methylbenzyl | M2 | 2/2 | 20 | 94 | 95 | — | — |
9 | Dimethylfumarate | 4-Bromobenzyl | M2 | 2/2 | 20 | 99 | 99 | — | — |
10 | Dimethylfumarate | 1-Phenylethyl | M2 | 2/2 | 20 | 98 | 98 | — | — |
11 | Dimethylfumarate | Benzyl | M4 | 4/4 | 40 | 98 | 98 | 97 | 98 |
12 | Dimethylfumarate | 4-Methoxybenzyl | M4 | 4/4 | 40 | 93 | 94 | 93 | 94 |
13 | Dimethylfumarate | 4-Methylbenzyl | M4 | 4/4 | 40 | 95 | 93 | 94 | 93 |
14 | Dimethylfumarate | 4-Bromobenzyl | M4 | 4/4 | 40 | 99 | 98 | 99 | 99 |
15 | Dimethylfumarate | 1-Phenylethyl | M4 | 4/4 | 40 | 98 | 97 | 97 | 98 |
16 | Dimethylfumarate | Benzyl | Q4e | 1/4 | 40 | 70 | 20 | 30 | 65 |
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