A continuous flow synthesis and derivatization of 1,2,4-thiadiazoles

Baumann, Marcus; Baxendale, Ian R.

doi:10.1016/j.bmc.2017.01.022

Cited by 12 publications

(4 citation statements)

References 26 publications

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“…Additions to nitriles to form amidinates (as in entry 12) are well-known for LiHMDS . Mechanistic studies below offer some thoughts on why analogous additions of NaHMDS to nitriles are rare …”

Section: Resultsmentioning

confidence: 99%

“…Adding [ 15 N]NaHMDS to unlabeled benzonitrile, 17 , shows label incorporation in both 17 and 58 . Thus, benzonitrile can be isolated in 86% yield using 1.1 equiv of NaHMDS and elevated temperatures (Table , entry 13), while amidine 58 can be isolated in 98% yield using 3.0 equiv of NaHMDS at 80 °C for 3 h and then 25 °C for 12 h. This odd temperature dependence in which heating accelerates the aminolysis but retards addition to the intermediate nitrile might be why nitrile-to-amidine conversions largely exploit LiHMDS rather than NaHMDS . Alternatively, it could just be a cultural preference for LiHMDS.…”

Section: Resultsmentioning

confidence: 99%

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Carbon–Nitrogen Bond Formation Using Sodium Hexamethyldisilazide: Solvent-Dependent Reactivities and Mechanisms

You,

Collum

2023

J. Am. Chem. Soc.

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The solvent-dependent reactivity of sodium hexamethyldisilazide (NaHMDS) toward carbon-centered electrophiles reveals reactions that are poorly represented or unrepresented in the literature, including direct aminolysis of aromatic methyl esters to give carboxamides, nitriles, or amidines, depending on the choice of solvent. SNAr substitutions of aryl halides and opening of terminal epoxides are also examined. A combination of 1H and 29Si nuclear magnetic resonance (NMR) spectroscopic studies using [15N]NaHMDS, kinetic studies, and computational studies reveals the complex mechanistic basis of the preferences for simple aryl carboxamides in toluene and dimethylethylamine and arylnitriles or amidines in tetrahydrofuran (THF). A prevalence of dimer- and mixed dimer-based chemistry even starting from the observable NaHMDS monomer in THF solution is notable.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Carbon–Nitrogen Bond Formation Using Sodium Hexamethyldisilazide: Solvent-Dependent Reactivities and Mechanisms

You,

Collum

2023

J. Am. Chem. Soc.

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“…In fact, compounds showing unselective inhibition of CYP11B2 and CYP11B1 might provide severe side effects, progressing to acute adrenal insufficiency and potentially fatal cardiovascular collapse . The compounds were synthesized using previously reported synthetic routes. − The functionalized thioimidazole species were assembled through a multicomponent one-pot process based upon a Marckwald reaction . For example, compound X1 was synthesized starting from dihydroxyacetone dimer, potassium thiocyanate, and the appropriately functionalized 2,4-dichlorobenzylic amine hydrochloride salt.…”

Section: Resultsmentioning

confidence: 99%

Discovery of a Potent Dual Inhibitor of Aromatase and Aldosterone Synthase

Tinivella,

Banchi,

Gambacorta

et al. 2023

ACS Pharmacol. Transl. Sci.

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“…In the described setup, it was possible to promote the safe handling of the hazardous trichloromethane sulfenyl chloride, a versatile reagent applied, due to inline quenching steps developed to eliminate malodourous and corrosive by‐products (Scheme ). The final products were obtained in very good yields, making this procedure a desirable one for the preparation of this type of heterocycles, which can be further modified for several applications …”

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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A continuous flow synthesis and derivatization of 1,2,4-thiadiazoles

Cited by 12 publications

References 26 publications

Carbon–Nitrogen Bond Formation Using Sodium Hexamethyldisilazide: Solvent-Dependent Reactivities and Mechanisms

Carbon–Nitrogen Bond Formation Using Sodium Hexamethyldisilazide: Solvent-Dependent Reactivities and Mechanisms

Discovery of a Potent Dual Inhibitor of Aromatase and Aldosterone Synthase

Flow Chemistry: Towards A More Sustainable Heterocyclic Synthesis

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