Efficient Diels-Alder Reaction of O-Quinone Electroenerated in a Flow Microreator
Authors: Yoshizawa Hirona , Tateno Hiroyuki , Atobe Mahito 
Published: February 2020

The Diels-Alder reaction is one of the most powerful carbon-carbon bond forming process1 and useful method for the construction of six-membered ring structures2. Especially, the Diels-Alder reaction of o-quinones has attracted much attention since its products are very important synthetic precursors for dye compounds and drug medicines. However, o-quinones are too reactive and unstable to store and not easy to handle because of their lability, that is, decomposition, isomerization, or polymerization often occur during storage3. Therefore, these o-quinones are usually prepared by the in situ oxidation of the corresponding catechols in the presence of a reaction partner. However, the oxidation potentials of the reaction partners are often the same or lower than those of the corresponding catechols, and therefore the presence of the partners would prevent the desired oxidation of the catechols. To avoid the decomposition of o-quinones and competing oxidation, catechols must be oxidized in the absence of organic substrate and then used immediately for the following reaction.

Flow microreactors are ideal for conducting such transformations because they enable the precise control of short-lived species. In doing so, they facilitate highly selective reactions that are difficult to achieve in a conventional reactor. In addition, flow microreactors offer advantages such as large specific interfacial area, short molecular diffusion distance, and short residence time in the reactors.

In this work, we have successfully demonstrated that a flow microreactor is extremely useful in controlling reactions involving an unstable o-quinone. The key features of the method are an effective o-quinone generation and its rapid use for the following reaction without decomposition in a flow microreactor.

We chose a Diels-Alder reaction between o-quinone generated from electrochemical oxidation of catechol and 6,6-dimethylfulvene as a model process (Scheme 1). The flow microreactor fabricated for the model reaction consists of two parts, an electrolysis part for the generation of o-quinone and a chemical reaction part for its rapid use for Diels-Alder reaction, as shown in Figure 1. This flow microreactor was constructed from platinum (Pt) plate and graphite plate. A spacer was used to leave a rectangular channel exposed, and the two electrodes were simply sandwiched together (area of the two electrode: 1×3 cm2). After connecting Teflon tubing to inlet and outlet, the cell was sealed with epoxy resin.

At first, we measured linear sweep voltammograms for the oxidation of catechol 1 and fulvene 3 in a conventional undivided cell. As a result, the oxidation potentials of 1 and 3 were relatively close to each other. This result indicates that the competing oxidation of 1 and 3would be unavoidable on the conventional batch type reactor.

Subsequently, we conducted preparative scale experiments of the model Diels-Alder reaction using a batch type cell and a flow microreactor. In the batch type cell, the desired product 4 was obtained in low yield (Table 1, entry 1). On the other hand, the yield of 4 was much improved by using the flow microreactor (Table 1, entry 2). This result apparently suggests that o-quinone could be generated effectively without interference of the fulvene oxidation, and in addition the generated o-quinone could be used rapidly for the reaction with fulvene without its decomposition.

In the presentation, we will also discuss about the effect of anode material, flow rate, and concentration of fulvene on the model reaction in the flow microreactor.

References

1) V. Nair, S. Kumar, G. Anikumar, J. S. Nair, Tetrahedron, 1995, 51, 9155-9166.

2) J. Choi, H. Park, H. J. Yoo, S. Kim, E. J. Sorensen, C. Lee, J. Am. Chem. Soc., 2014, 136, 9918–9921.

3) T. Kashiwagi, F. Amemiya, T. Fuchigami, M. Atobe, Chem. Commun., 2012, 48, 2806-2808.

Figure 1