Developing benign syntheses using ion pairs <i>via</i> solvent-free mechanochemistry

Ortiz-Trankina, Lianna N.; Crain, Jazmine; Williams, Carl H.; Mack, James

doi:10.1039/d0gc01116a

Cited by 13 publications

(15 citation statements)

References 38 publications

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“…(3)], although in a moderate 40 % yield. This result stays in line with previous observations, [65,66] showing that nucleophilic reactivity of anions under solvent‐free conditions is strongly controlled by their counter‐ion pairing. The effect was interpreted in the framework of hard‐soft acid‐base (HSAB) theory, [14] explaining the enhanced nucleophilicity of F − in CsF as a result of a mismatched soft‐hard ion pair.…”

Section: Resultssupporting

confidence: 93%

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates**

et al. 2022

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An expansion of the solvent‐free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent‐based synthesis. Herein a new mechanochemical method was developed for nucleophilic substitution of alcohols using fluoro‐N,N,N′,N′‐tetramethylformamidinium hexafluorophosphate (TFFH) and K2HPO4 as an alcohol‐activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 31–91 % yields. The complete stereoinversion occurred for the SN2 reaction of (R)‐ and (S)‐ethyl lactates. Substitution with halide anions (F−, Br−, I−) and oxygen‐centered (CH3OH, PhO−) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients has been demonstrated.

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Section: Resultssupporting

confidence: 93%

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates**

et al. 2022

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“…3), although in a moderate 40% yield. This result stays in line with previous observations, 60,61 showing that nucleophilic reactivity of anions under solvent-free conditions is strongly controlled by their counter-ion pairing. The effect was interpreted in the framework of hard-soft acid-base (HSAB) theory, 14 explaining the enhanced nucleophilicity of F − in CsF as a result of a mismatched soft-hard ion pair.…”

Section: Methodssupporting

confidence: 93%

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates

Dalidovich

Nallaparaju

Shalima

et al. 2021

Preprint

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An expansion of the solvent-free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent-based synthesis. Herein we report a new mechanochemical method for nucleophilic substitution of alcohols using fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (TFFH) and K2HPO4 as an alcohol-activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 40–91% yields. The complete stereoinversion occurred for the SN2 reaction of (R)- and (S)-ethyl lactates. Substitution with halide anions (F−, Br−, I−) and oxygen-centered (CH3OH, PhO−) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients (APIs) has been demonstrated.

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“…[55] Importantly, imidazole, an unavoidable by-product in reactions with CDI can be repurposed to act as an in situ generated base as demonstrated in the synthesis of hydroxamic acids 12, [56] or in telescopic mechanochemical transformations such as the onepot/two-step synthesis of unsymmetrical ureas 14 (Scheme 4). [57] The ability of mechanochemistry to avoid using [58] or producing toxic substances was put again in evidence during the oxidation of noble metals like gold and palladium into useful metal salts by ball milling (Scheme 5). [59] The mechanochemical approach enabled the oxidation of metal pellets, metal powder or metal wires into well-defined salts using Oxone® [60] and halide salts, thus preventing the use of hazardous reagents such as aqua regia.…”

Section: Gc 3: Less Hazardous Chemical Synthesismentioning

confidence: 99%

“…The ability of mechanochemistry to avoid using [58] or producing toxic substances was put again in evidence during the oxidation of noble metals like gold and palladium into useful metal salts by ball milling (Scheme 5). [59] …”

Section: Mechanochemistry and The Twelve Principles Of Green Chemistrymentioning

confidence: 99%

Sustainability Assessment of Mechanochemistry by Using the Twelve Principles of Green Chemistry

2021

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In recent years, mechanochemistry has been growing into a widely accepted alternative for chemical synthesis. In addition to their efficiency and practicality, mechanochemical reactions are also recognized for their sustainability. The association between mechanochemistry and Green Chemistry often originates from the solvent-free nature of most mechanochemical protocols, which can reduce waste production. However, mechanochemistry satisfies more than one of the Principles of Green Chemistry. In this Review we will present a series of examples that will clearly illustrate how mechanochemistry can significantly contribute to the fulfillment of Green Chemistry in a more holistic manner.

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Developing benign syntheses using ion pairs via solvent-free mechanochemistry

Abstract: Solvent-free mechanochemical conditions have been developed to investigate the significance of ion pairing and the use of weak bases for driving forward nucleophilic substitution reactions.

Cited by 13 publications

References 38 publications

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates**

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates**

Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates

Sustainability Assessment of Mechanochemistry by Using the Twelve Principles of Green Chemistry

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