One‐Pot Synthesis of Diverse γ‐Lactam Scaffolds Facilitated by a Nebulizer‐Based Continuous Flow Photoreactor

Abstract

The use of a modified prototype continuous flow reactor (CFR) as a pivotal part of a number of versatile singlet oxygen‐mediated reaction sequences is presented herein. These sequences target rapid access to structural complexity and diversity. The prototype reactor achieves high conversions and productivities by attaining large specific surface areas for these biphasic reactions. In the reactor, the reaction solution is nebulized (using either oxygen or air) and the resulting aerosol is irradiated by an LED jacket that surrounds the Pyrex reaction chamber. The one pot procedures developed herein are, according to many different criteria, both highly efficient and green. The key common intermediates and the source of both the complexity and variety of the final products are N‐acyl imminium ions (NAI; protonated N‐acyl enamines). The initial substrates are simple and readily accessible furans and the diverse array of products is composed of different complex γ‐lactams. Many of the products are of particular interest due to their close relationships to known biologically active molecules.

Overcoming mass and photon transfer limitations in a scalable reactor: Oxidation in an aerosol photoreactor

“…Recently, several singlet oxygen mediated reactions such as photooxidation of β-citronellol, α-terpinene, (5-methylfuran-2-yl)methanol [45], synthesis of cyclopent-2-enones from furans [46] and synthesis of diverse γ-lactam scaffolds [47] were studied in a novel aerosol photoreactor. Full conversions were achieved for all the reactions [45][46][47]. In this reactor concept, each droplet works as a microreactor.…”

“…If the droplets were assumed to move at the same velocity with the gas, the residence time would be one min. It seems that one minute is too long for an aerosol photoreactor operation since the authors did not observe much change in the conversion with varying liquid flow rates, nebulizing gas pressures or concentration of the reactants [45][46][47]. In order to assess the aerosol photoreactor performance, the operational parameters such as droplet sizes, aerosol number concentration, which is defined as the number of droplets in a unit volume, light intensity and residence time still need to be determined.…”

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

“…The reactor concept is easily scalable by simply increasing the number of nebulizers. An aerosol photoreactor called NebPhotOX has recently been operated several times and has been proved to work extremely efficient [ 46 – 48 ]. In that work, the liquid reactants were nebulized into a glass chamber that was wrapped with LED strips.…”

“…Singlet oxygen is a highly reactive state of oxygen, which can be formed by some photosensitizers or dyes when an appropriate light source is used. The authors performed an ene reaction of β-citronellol and Diels–Alder reactions of α-terpinene and (5-methylfuran-2-yl)methanol [ 46 ] as well as the synthesis of cyclopent-2-enones from furans [ 47 ] and the synthesis of diverse γ-lactam scaffolds [ 48 ]. Conversions larger than 90% were achieved for all reactions [ 46 – 48 ].…”

Scalable Continuous Vortex Reactor for Gram to Kilo Scale for UV and Visible Photochemistry

“…[14][15] The development of flow photochemistry has been facilitated by devlopments in reactor design, for example, there are several reactor designs that address the effective and safe addition of gases such as the photochemically generated singlet oxygen. [16][17][18][19][20][21][22][23][24][25][26] The recent development in applications of visible photochemistry has also, in part, been driven by advances in Light-Emitting Diodes (LEDs) [27][28] which provide inexpensive high intensity visible light sources. LEDs emitting in the UVA region are also available but this technology is still nascent, with the LEDs having lower powers and higher cost, limiting so far the large-scale application of UV LEDs for photochemistry.…”