Continuous flow upgrading of glycerol toward oxiranes and active pharmaceutical ingredients thereof

Morodo, Romain; Gérardy, Romaric; Petit, Guillaume; Monbaliu, Jean‐Christophe M.

doi:10.1039/c9gc01819k

Cited by 49 publications

(59 citation statements)

References 54 publications

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“…These factors have prompted the search for alternative procedures based on sustainable methods and renewable raw materials to synthesize ECH [44]. The most prevalent synthetic procedures for glycerol chlorination [66,67] are based on the reaction of glycerol with an aqueous solution of hydrochloric acid [34,56,[68][69][70][71][72][73]. The synthetic process has been scaled up to an industrial scale [74,75].…”

Section: Synthesis Of Epichlorohydrinmentioning

confidence: 99%

Preparation and Uses of Chlorinated Glycerol Derivatives

et al. 2020

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Crude glycerol (C3H8O3) is a major by-product of biodiesel production from vegetable oils and animal fats. The increased biodiesel production in the last two decades has forced glycerol production up and prices down. However, crude glycerol from biodiesel production is not of adequate purity for industrial uses, including food, cosmetics and pharmaceuticals. The purification process of crude glycerol to reach the quality standards required by industry is expensive and dificult. Novel uses for crude glycerol can reduce the price of biodiesel and make it an economical alternative to diesel. Moreover, novel uses may improve environmental impact, since crude glycerol disposal is expensive and dificult. Glycerol is a versatile molecule with many potential applications in fermentation processes and synthetic chemistry. It serves as a glucose substitute in microbial growth media and as a precursor in the synthesis of a number of commercial intermediates or fine chemicals. Chlorinated derivatives of glycerol are an important class of such chemicals. The main focus of this review is the conversion of glycerol to chlorinated derivatives, such as epichlorohydrin and chlorohydrins, and their further use in the synthesis of additional downstream products. Downstream products include non-cyclic compounds with allyl, nitrile, azide and other functional groups, as well as oxazolidinones and triazoles, which are cyclic compounds derived from ephichlorohydrin and chlorohydrins. The polymers and ionic liquids, which use glycerol as an initial building block, are highlighted, as well.

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Section: Synthesis Of Epichlorohydrinmentioning

confidence: 99%

Preparation and Uses of Chlorinated Glycerol Derivatives

et al. 2020

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“…The separation of these two products is performed by an in‐line membrane separation system, which allows the first product to be collected in the aqueous phase, while the second is collected in MTBE. This heterocycle can be further used as a synthetic precursor to relevant APIs bearing β‐amino alcohol moieties (e.g., propranolol, alprenolol and naftopidil) …”

Section: Heterocyclic Synthesismentioning

confidence: 99%

Flow Chemistry: Towards A More Sustainable Heterocyclic Synthesis

2019

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Flow Chemistry is a revolutionary field in Organic Chemistry. By changing the conventional methods and apparatus applied in the chemical synthesis, flow chemistry emerges as a game changer for organic synthesis laboratories, in both academia and industries. Considered as a sustainable practice, flow processes play an important role in the development of fine chemical products and in drug discovery development pro- [a] The main advantages of flow chemistry are that it allows the reaction to be carried out safely with high selectivity, high reproducibility and reduced energy consumption/carbon footprint. These features make this emerging technology for organic synthesis desirable for green and sustainable chemical synthesis, giving the chemist time for work planning and design, instead of using it in repetitive tasks, [5b,12] as expressed by the CHEM21 project by awarding a green flag for continuousflow reactions, in opposition to an amber flag for those performed under batch conditions. [13] Pedro Brandão received his MSc in Pharmaceutical Sciences from the Faculty of Pharmacy -University of Porto, in 2011. Pursuing his passion on studies in the field of Drug Discovery and Development, he is currently undergoing his PhD studies in Chemistry, in the field of Catalysis and Sustainability. His main focus of work is the discovery of new drug candidates through sustainable techniques. Marta Pineiro received her Ph.D. in Organic Chemistry in 2003 in the University of Coimbra, Portugal, and since 2002 has been enrolled at the University of Coimbra, being at present Auxiliary Professor. Her research interests are in the area of sustainable organic synthesis, microwave-assisted organic synthesis and synthesis and biological applications of tetrapyrrolic macrocycles. Teresa M. V. D. Pinho e Melo studied Chemistry at the University of Coimbra, where she graduated in 1985, got her M. 7191CPBA) as the oxidizing agent, avoiding the handling of this expensive and explosive reagent. [25] Recently, Morodo et al. explored the synthesis of two very important oxiranes (epichlorohydrin and glycidol) from biobased glycerol, under flow conditions. As depicted in Scheme 1, and using pimelic acid as the catalyst (10 mol-%), a sequential hydrochlorination/dichlorination process allows high conversion of glycerol (> 99 %) into 1,3-dichloro-2-propanol, followed by the quantitative conversion into a separable mixture of glycidol and epichlorohydrin (2:3). The separation of these two products is performed by an in-line membrane separation system, which allows the first product to be collected in the aqueous phase, while the second is collected in MTBE. This heterocycle can be further used as a synthetic precursor to relevant APIs bearing -amino alcohol moieties (e.g., propranolol, alprenolol and naftopidil). [26] Scheme 1. Sequential flow setup for the preparation of glycidol and epichlorohydrin, important APIs synthetic intermediates.Scheme 3. Synthesis and inline purification of a bicyclic aziridine (SGMR = silicon-glass microfluidic react...

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“…[1][2][3][4] Typical amination procedures exploit the inherent nucleophilic nature of nitrogen for its insertion on activated electrophilic substrates. [5][6][7][8][9][10][11] Alternative methods relying on the umpolung of nitrogen, known as electrophilic aminations, are also abundantly documented in the literature. [12][13][14][15][16][17][18][19] A variety of electrophilic amination reagents have been reported, among which azodicarboxylates, [23][24][25][26][27][28][29] diazoesters, 30 haloamines, [30][31][32] hydroxylamines and derivatives, 30,[32][33][34][35] oxaziridines, 11,36 as well as nitroso derivatives are documented (Fig.…”

Section: Introductionmentioning

confidence: 99%