Due to their intrinsic physical properties, which includes being able to perform as volatile liquids at room and biological temperatures, fragrance ingredients/intermediates make ideal candidates for continuous-flow manufacturing. This review highlights the potential crossover between a multibillion dollar industry and the flourishing sub-field of flow chemistry evolving within the discipline of organic synthesis. This is illustrated through selected examples of industrially important transformations specific to the fragrances and flavours industry and by highlighting the advantages of conducting these transformations by using a flow approach. This review is designed to be a compendium of techniques and apparatus already published in the chemical and engineering literature which would constitute a known solution or inspiration for commonly encountered procedures in the manufacture of fragrance and flavour chemicals.
A sequence of seven reactions (stereocontrolled allylation, Mitsunobu reaction, ring closing metathesis, and amino/amido intramolecular nucleophilic addition) efficiently convert the inexpensive starting 2‐piperidine ethanol into a small library of enatiomerically pure nitrogen containing compounds characterized by three new scaffolds that present a relevant diversity. This simple approach encroaches the further exploration of the chemical space.
A continuous-flow preparation of 2-benzoxazolinone via the Hofmann rearrangement of salicylamide has been implemented employing trichloroisocyanuric acid as the stable and atom-economic chlorinating agent. The system was optimized to avoid solid accumulation and allow the preparation of hundreds of grams of the pure desired material over a working day. Furthermore, a trichloroisocyanuric acid (TCCA)-based chlorination of 2-benzoxazolone to the corresponding 5-chloro derivative was also carried out under batch conditions.
The hydroxy-pyrazole and 3-hydroxy-oxindole motifs have been utilised in several pharma and agrochemical leads but are distinctly underrepresented in the scientific literature due to the limited routes of preparation. We have developed a one-pot procedure for their synthesis starting from simple isatins. The method employs cheap and easy-to-handle building blocks and allows easy isolation.
The Front Cover shows a playful representation of the fascination to explore, that always moved science forward. In particular, the exploration of the Chemical Space is a challenging experience that excites creativity and enthusiasm of the organic chemists. The 2‐piperidine ethanol appears as a kite in the hands of a bold researcher to give vent to the imagination, looking for new structures and landing on known chemical entities. More information can be found in the Full Paper by D. Passarella et al.
We
have prepared a library of functionalized quinolines through
the magnesiation of 7-chloroquinolines under mild conditions, employing
both batch and continuous flow conditions. The preparation involved
the generation of mixed lithium-magnesium intermediates, which were
reacted with different electrophiles. Mixed lithium-zinc reagents
allowed the synthesis of halogenated and arylated derivatives. Some
of the synthesized 4-carbinol quinolines have shown interesting antiproliferative
properties, their hydroxyl group being a suitable amino group bioisostere.
We also report a two-step approach for optically active derivatives.
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