A Sustainable, Semi‐Continuous Flow Synthesis of Hydantoins

Vukelić, Stella; Koksch, Beate; Seeberger, Peter H.; Gilmore, Kerry

doi:10.1002/chem.201602609

Cited by 20 publications

(19 citation statements)

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“…44 Exchange of HCl for CO 2 gas provides access to a class of heterocycles called hydantoinsthough removal of the oxygen gas from the singlet oxygen generator is first required for this two-step CAS. 45 Finally, replacement of the cyanide with a different carbon nucleophile, malononitrile, provides access to a-cyanoepoxides through a two-stage oxidation, where singlet oxygen generates both the imine and an equivalent of hydrogen peroxide, that in the second module oxidizes the intermediate electron-poor a,b-unsaturated ester into the corresponding epoxide (Fig. 25).…”

Section: Cas 1 (Artemisinin Derivatives)mentioning

confidence: 99%

How to approach flow chemistry

2020

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Section: Cas 1 (Artemisinin Derivatives)mentioning

confidence: 99%

How to approach flow chemistry

2020

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“…Briefly, the unprotected primary amine undergoes photooxidative cyanation in the presence of oxygen, to afford the unstable α‐amino nitrile intermediate, which reacts with carbon dioxide in the presence of N , N ‐diisopropylethylamine (DIEA) to promote the carboxylation rearrangement step leading to the final hydantoin derivatives (52–84 % yields). The presence of an aromatic substituent allows higher yields in the examples reported …”

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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“…Flow chemistry technology is widely used in many synthetic organic reactions at both laboratory and industrial scale [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. There are a number of benefits of using continuous-flow (CF) chemistry.…”

Section: Introductionmentioning

confidence: 99%

N-Acetylation of Amines in Continuous-Flow with Acetonitrile—No Need for Hazardous and Toxic Carboxylic Acid Derivatives

2020

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A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.

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A Sustainable, Semi‐Continuous Flow Synthesis of Hydantoins

Cited by 20 publications

References 44 publications

How to approach flow chemistry

How to approach flow chemistry

Flow Chemistry: Towards A More Sustainable Heterocyclic Synthesis

N-Acetylation of Amines in Continuous-Flow with Acetonitrile—No Need for Hazardous and Toxic Carboxylic Acid Derivatives

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