UV PhotoVap: Demonstrating how a simple and versatile reactor

Article Cite This: Org. Process Res. Dev. XXXX, XXX, XXX−XXX

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UV PhotoVap: Demonstrating How a Simple and Versatile Reactor Based on a Conventional Rotary Evaporator Can Be Used for UV Photochemistry Charlotte A. Clark,† Darren S. Lee,† Stephen J. Pickering,‡ Martyn Poliakoff,*,† and Michael W. George*,†,§ †

School of Chemistry and ‡Department of Mechanical, Materials and Manufacturing Engineering, The University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom § Department of Chemical and Environmental Engineering, The University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China S Supporting Information *

ABSTRACT: We report the use of a simple rotary evaporator as a semi-continuous UV photochemical reactor. By generation of a thin film from the rotation of a flask, better light penetration is achieved, and in this work we used high-power Hg lamps to enable the direct irradiation of molecules with UV light. The intramolecular [2 + 2] photocycloaddition of Cookson’s dione and the intermolecular [2 + 2] photocycloaddition of maleimide with 1-hexyne were used as test reactions to examine the effectiveness of this reactor. High productivities, equivalent to 210 g h−1, were obtained for the simple intramolecular reaction, demonstrating the scalability of the reactor. The effects of flask size, reaction mixture volume, and use of borosilicate or quartz glassware were also investigated.

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tube flow reactor (PTFR) for UV photochemical synthesis.63 Building upon their earlier work with FEP reactors, they designed the PTFR to meet several criteria for scaling up UV photochemical processes: (i) the reactor should be capable of delivering ≥1 kg per day; (ii) it should encapsulate the UV as effectively as in an FEP reactor; (iii) it should have a small footprint to fit within a standard fume hood; and (iv) the FEP should be replaced with a more durable, UV-transparent tubing. The reactor operates with safe containment of a high-power (1−5 kW) UV source and has been demonstrated with reactions on a variety of scales while reducing reaction times 10-fold compared with their previous FEP reactors.63 Our original PhotoVap report focused on using visible light to initiate photochemical reactions, primarily ones involving oxygen. In this paper, we extend the concept of using a rotary evaporator for thin-film generation and show that this relatively simple approach has considerable potential for UV photochemistry.

INTRODUCTION Photochemical processing is undergoing a renaissance,1−9 and this in part is driven by an increasing focus on flow and continuous processing in both academia and industry.10−21 Flow chemistry offers particular advantages for photochemistry, where limitations of light penetration make the scale-up of batch processes more difficult. Much of the current interest has involved visible-light photochemistry, particularly in the area of photoredox catalysis.22−30 The increasing number of researchers working in this field has helped fuel the demand for effective and efficient photoreactors and new experimental approaches.31−33 Our reactors have previously employed visible light-emitting diodes (LEDs),22,34−40 and such light sources were also used in our recent photoreactor41 for conventional solvents, which is based on a rotary evaporator (we styled this the PhotoVap), where generation of a thin film enabled better light penetration and hence increased reaction efficiency. The PhotoVap can be operated in a semi-continuous manner, and we have demonstrated that despite its simplicity, it is flexible, allowing different modes of operation on multiple scales simply by changing the size of the flask. It has efficient gas−liquid mass transfer as a consequence of the large surface area of the thin film generated upon spinning.41 For UV photochemical flow reactions, a major innovation was reported by Berry and Booker-Milburn, who described the construction of a reactor consisting of a coil (single or multilayered) of fluorinated ethylene propylene (FEP) tubing wrapped around a transparent housing containing a Hg lamp.42 Since their initial report, this approach has been exploited by many researchers43−61 and equipment manufacturers62 around the world. They recently reported a new high-capacity parallel © XXXX American Chemical Society

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RESULTS AND DISCUSSION Safety is paramount in UV photolysis experiments, particularly the containment of high-power UV sources and radiation. Our approach has been to contain the reactor within a single fume hood, where the solid walls enclose the UV radiation on three sides and the glass sash is equipped with a removable dark-red plastic filter that provides enhanced blocking of hard UV light and most of the visible spectrum too (see the Supporting Information). The principle of the reactor is the same as that described previously for visible light but with two main Received: January 31, 2018 Published: March 28, 2018 A

DOI: 10.1021/acs.oprd.8b00037 Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Organic Process Research & Development

Article

Figure 1. Simplified schematic showing the general setup of the UV PhotoVap. The inset is a photograph from above showing the air-cooled Hg lamps in position around the flask.

differences: (i) The visible-light LEDs have been replaced by high-power mercury lamps (1400−2000 W per lamp; see the Supporting Information for more details). These Hg lamps provide broadband emission that can be used to excite a range of different chromophores. (ii) In this UV setup, inert nitrogen gas is delivered into the reactor during operation, with a mass flow controller to control the delivery rate. Often the presence of oxygen has a deleterious effect on reactions involving UV light by quenching excited states and lowering the productivity. The operation of the reactor is as described previously: the desired volume of reaction solution is delivered and removed using two peristaltic pumps, while the temperature and rotation speed are controlled using the built-in rotary evaporator functions (Figure 1), with all functions under the control of a computer. The two UV lamps were positioned directly facing the thin film that is formed by rotation of the flask. In this arrangement, the water bath was used to maintain a constant temperature of the flask (all reactions were run with an average internal temperature during irradiation of 37 °C). For some reactions, the reactor was operated semi-continuously, where the flask was filled, irradiated, and then emptied on an automated cycle. For each experiment, the temperature was continually monitored during irradiation by internal and external thermocouples. Typically, during the course of operation the temperature increased (at a rate of ca. 3.5 °C min−1). Despite any increase in temperature, the amount of solvent evaporation was found to be minimal (ca. 200 g h−1. Also, because of the simplicity of the reactor design, issues that could lead to downtime, such as reactor fouling, can be easily minimized simply by swapping the flask for a clean one. The reactor was also run using a more complex intermolecular reaction involving two components: the [2 + 2] cycloaddition of maleimide (3) with 1-hexyne (4) (Scheme 2). The reaction proceeds via excitation of 3, which subsequently reacts with 4 in a [2 + 2] cycloaddition yielding the bicyclic product 5. An added complication is that 4 is relatively volatile (bp 71.3 °C), allowing us to probe any possible reagent loss during operation. Moderate yields of 5 (42%) were obtained using a single 1.4 kW lamp within 2 min of irradiation time (Table 2, entry 1). Doubling the lamp power (Table 2, entry 2) by adding a second 1.4 kW lamp gave a similar yield in half of the time (60 B



Article

Table 1. Comparison of Conversions of 1 and Yields and Productivities of 2 over a Range of Reactor Parametersa entry

lamp power/kW

irradiated volume/mL

[1]/M

photolysis time/s

conversion/%

yield/%

equivalent productivityb/g h−1

1 2 3 4c 5 6 7 8d

2.0 2.0 2.0 2.0 3.4 3.4 3.4 3.4

30 30 30 30 100 100 100 100

0.25 0.25 0.25 0.25 0.5 0.5 0.5 0.5

30 45 60 150 30 60 90 60

63 84 97 94 35 63 88 64

58 77 90 80 34 63 83 59

55.1 56.4 46.2 22.2 148 198.7 210.6 170.5

Unless specified otherwise, the reaction was conducted in batch mode in EtOAc using a 1 L round-bottom quartz flask rotating at 150 rpm with N2 bubbling through the solution at 30 sccm (sccm = standard cubic centimeters per minute). bEquivalent productivity takes into account the time to pump material into and out of the vessel (processing time) and was calculated as ([1] (M) × irradiated volume (mL)/1000) × yield × molecular weight × [3600 s/(irradiation time (s) + processing time (s))]. cThe reaction flask was a 1 L borosilicate round-bottom flask. dThe reaction was conducted by running the reactor as a semi-continuous process. a

It was reasoned that a UV cut-off at ca. 250 nm might allow optimum irradiation for this reaction; therefore, we tried using an internal UV filter simply by replacing the CH3CN solvent with EtOAc (UV cutoff < 256 nm). However, repeating the reaction in EtOAc gave results similar to those for reactions conducted in CH3CN. Several external filters were also applied, this time by using the thin film that is generated on the outside of the flask as it rotates in the water bath. Aqueous CuSO4 and KI were used with minimal improvements in productivity (see the Supporting Information for further details). An alternative setup was also tried with this reaction, one that placed a 2 kW lamp above the flask. However, the productivity obtained from this setup was lower, with lower yields and more issues with fouling/overheating (see the Supporting Information for further details). While the yields for this reaction were typically lower than reported for other reactors, this reaction is very challenging with many possibilities for byproduct formation and fouling; however, productivities of up to 14.0 g h−1 were obtained, further demonstrating the potential of the reactor for scalable UV photochemistry.

Scheme 2. [2 + 2] Photocycloaddition of Maleimide (3) with 1-Hexyne (4) To Form Bicycle 5

s). Changing the flask to borosilicate (Table 2, entry 3) gave a drop in productivity of ca. 50%, as expected because this glassware filters out some of the UV light. In our visible-light experiments, we observed an increase in productivity upon increasing both the flask size and irradiated solution volume, and we were keen to investigate this effect for the UV reactor.41 For this reaction, upon increasing the irradiated solution volume we observed a corresponding increase in both productivity and mass balance (Table 2, entry 4), attributable to a reduction in the amount of polymeric byproduct formed. This was also apparent upon visual inspection of the flask, where considerably less reactor fouling was observed when a larger irradiation volume was used. The use of larger volumes is expected to increase the amount of mixing and reduce the potential for over-irradiation. Clearly this reaction suffers from some secondary irradiation or competing processes when quartz glassware is used because the conversion is quite high but the yield is roughly half of that with borosilicate. Additional experiments with an excess (5 or 10 equiv) of 1-hexyne (Table 2, entries 5 and 6) showed little increase in the yield compared to that with 1.5 equiv (Table 2, entry 2), which suggests that any evaporation of this reagent is minimal despite its volatility and low boiling point (71.3 °C).

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CONCLUSION

In this report we have demonstrated that a simple rotary evaporator can be converted into an effective UV photochemical reactor by addition of high-power UV lamps; the reactor is capable of producing up to 210 g h−1. Two reactions were studied to enable different properties of the reactor to be studied. For the simple intramolecular reaction of 1 to give 2, high productivities were obtained. For the more complex intermolecular reaction of 3 with 4 to form 5, the yields were moderate because of possible over-irradiation of the products

Table 2. [2 + 2] Photocycloaddition of 3 with 4 To Form 5 Using Various Parameters in the Reactora entry

lamp power/kW

irradiated volume/mL

photolysis time/s

mass balance/%

conversion/%

yield/%

equivalent productivityb/g h−1

1 2 3c 4 5d 6e

1.4 2.8 2.8 2.8 2.8 2.8

30 30 30 100 30 30

120 60 60 60 60 60

52 46 79 80 54 51

81 83 25 29 82 79

42 38 20 23 44 40

5.7 9.0 4.7 14.0 10.6 9.4

a

Unless specified otherwise, the reaction was conducted with the reactor run semi-continuously. All of the reactions were run in CH3CN using a 1 L round-bottom quartz flask rotating at 150 rpm with N2 bubbling through the solution at 30 sccm. bEquivalent productivity takes into account the time to pump material into and out of the vessel (processing time) and was calculated as ([3] (M) × irradiated volume (mL)/1000) × yield × molecular weight × [3600 s/(irradiation time (s) + processing time (s))]. cThe reaction flask was a 1 L borosilicate round-bottom flask. dThe reaction was conducted using 5 equiv of 4. eThe reaction was conducted using 10 equiv of 4. C



Article

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and starting materials. During operation, no evidence for the evaporation of volatile reagents was observed, suggesting that the heat generated by the lamps can be effectively managed using the water bath. The simplicity of the design and availability of the equipment makes this a viable and inexpensive option for anybody seeking the rapid scale-up of a UV photochemical process.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.oprd.8b00037. Further details of the reactor, processing times, properties of the lamps and screens used, experimental details, and the 1H and 13C NMR assignments and spectra for the compounds (PDF).

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: martyn.poliakoff@nottingham.ac.uk. *E-mail: [email protected]. ORCID

Darren S. Lee: 0000-0002-8288-1838 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the EPSRC (Grant EP/P013341/1), The University of Nottingham EPSRC Impact Acceleration Fund (EP/ K503800/1) and The University of Nottingham Hermes Fellowship Scheme funded through HEIF for supporting this work. We also thank M. Dellar, C. Dixon, P. Fields, M. Guyler, D. Lichfield, M. McAdam, R. Wilson, and R. Meehan for technical support at the University of Nottingham.

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UV PhotoVap: Demonstrating how a simple and versatile reactor

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