Mustard Carbonate Analogues as Sustainable Reagents for the Aminoalkylation of Phenols

Annatelli, Mattia; Trapasso, Giacomo; Salaris, Claudio; Salata, Cristiano; Castellano, Sabrina; Aricò, Fabio

doi:10.1002/ejoc.202100328

Cited by 5 publications

(7 citation statements)

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“…A series of experiments were then conducted employing, as the selected DAC, diethyl carbonate that gave the best results also in the previously reported investigations in autoclave under pressure. 11 Indeed in this case the aminoalkylated phenol 3 was obtained in good yield (92–93%) after 30 minutes at both 200 and 220 °C. Halving the reaction time led to a small decrease in the isolated yield (84%).…”

Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 75%

“…It is noteworthy that our previous reactions carried out under pressure in a stain-less steel autoclave required 8 hours reaction time to achieve similar results. 11 In conclusion, the MW-assisted reaction of phenols employing -aminocarbonate showed to be a robust approach for their direct aminoalkylation reaction. For the two-steps procedure, optimized reaction conditions encompass the use of an excess of -aminocarbonate (1.5 mol ratio) at 220 °C for seven minutes.…”

Section: Feature Synthesismentioning

confidence: 89%

“…Phenols p -substituted with electron-withdrawing groups (NO 2 and CN) were quantitatively converted to the related products 5c and 5d ; again, best results were obtained using acetonitrile as solvent. It is worth nothing that these substrates, when previously reacted in autoclave, 11 poorly yielded the desired aminoalkylated products, meanwhile MW-assisted reaction resulted in very efficient NGP-driven alkylation. Similarly, N , N -dimethyl-2-(2-naphthoxy)ethanamine ( 5e ) was obtained from β-naphthol in excellent yield (>93%).…”

Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 99%

“…Inspired by our recent study on the one-pot aminoalkylation procedure for substituted phenols, 11 the feasibility of this reaction via microwave irradiation was also investigated. Therefore, phenol, 2-(dimethylamino)ethanol, and a DAC were reacted under MW in the presence of potassium carbonate as a base (Scheme 6 , Table 4 ).…”

Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 99%

“…10 More recently, a one-pot procedure for the introduction of N,N-dialkylethylamine moiety via in situ formation of a -aminocarbonate was also reported. 11 This simple alkylation approach relies on the reaction of an aminoalcohol with a nucleophile in the presence of DEC (Scheme 3). The one-pot alkylation via mustard carbonates avoids the use of mustard gas chemistry to insert amine side chains into pharmacophore scaffolds and, therefore, it represents a safer and a chlorine-free direct alcohol substitution, which is a key green chemistry research area for pharmaceuticals manufacturers.…”

Section: Feature Synthesismentioning

confidence: 99%

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Microwave-Assisted Aminoalkylation of Phenols via Mustard Carbonate Analogues

et al. 2022

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In this work we explored a MW-assisted chlorine-free direct phenol substitution, which was indicated as a key Green Chemistry research area for pharmaceuticals manufacturers. The reaction of β-aminocarbonates (mustard carbonates) with several substituted phenols in the presence of a polar solvent (acetonitrile or butanol) led to the related aminoalkylated products via the anchimeric assistance of the nitrogen incorporated in the organic carbonate backbone. The aminoalkylation required short reaction time (7 minutes) and the related products were isolated in high yield (> 90%) via quick liquid-liquid extraction or column chromatography depending on the solvent employed. Furthermore, MW irradiation also showed to promote the one-pot aminoalkylation of phenol in excellent yield. In this approach a β-aminoalcohol was reacted with phenol in the presence of diethyl carbonate, used for the in-situ formation β-aminocarbonate, key intermediate in the consequent anchimerically driven alkylation. The resulting product, namely N,N-dimethyl-2-phenoxyethanamine, was isolated as pure in almost quantitative yield.

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Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 75%

Section: Feature Synthesismentioning

confidence: 89%

Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 99%

Section: Table 1 Optimization Of the Reaction Condition...mentioning

confidence: 99%

Section: Feature Synthesismentioning

confidence: 99%

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Microwave-Assisted Aminoalkylation of Phenols via Mustard Carbonate Analogues

et al. 2022

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Reaction Pathways in Carbonates and Esters

Tundo,

Aricò

2023

ChemSusChem

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This review reports on the competition/collaboration among intertwined base‐catalyzed acyl cleavage bimolecular mechanism (BAc2)/base‐catalyzed alkyl cleavage bimolecular mechanism (BAl2) or the related acid catalyzed mechanisms AAc2/AAl2 and AAl1 concerning Carbonates chemistry also in comparison with Esters reactivity. A consistent analysis of the experimental data so far available in the literature led to proposing a Model outlining the differences in energy profiles among the above‐mentioned reaction mechanisms. The reactions involving Carbonates are so tightly interconnected that the formation of the final product is driven by a precise not interfering sequence of BAc2‐BAl2 (or AAl2‐AAc2) mechanisms. When entropic effect (in cyclizations) or an anchimneric effect (mustard carbonates, isosorbide methylation) are involved, the difference in Gibbs activation energy is reduced allowing chemical transformations that would normally require higher temperatures. In these cases (intramolecular alkylation, cyclisation reaction, and alkylation by mustard carbonates) only a catalytic amount of base is required as the leaving group CH3OCOO‐ decomposes restoring the base. As Green Chemistry is concerned, syntheses with much lower environmental impact are achieved with Carbonates when compared with the corresponding ones involving Chlorine chemistry.

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Nitrile Furanics via Copper‐Catalyzed Dehydration of Aldoximes and Knoevenagel Condensation

Annatelli,

Sadraoui,

Trapasso

et al. 2024

Eur J Org Chem

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In this work two synthetic approaches to introduce nitrile moieties into bio‐based derived furanic compounds were investigated, i.e., dehydration of aldoximes and Knoevenagel condensation. Both methodologies have been first tested and optimized on furfural and thus exploited on 5‐hydroxymethyl‐2‐furfural (HMF) and 5,5’‐oxy(bismethylene)‐2‐furaldehyde (OBMF). The syntheses of furfural, HMF and OBMF aldoximes were efficiently conducted (also in large scale) under mild reaction conditions and short reaction time. The subsequent dehydration to nitrile furanic compounds was carried out in the presence of catalytic amount of copper acetate monohydrate. Furthermore, Knoevenagel condensations were performed on furfural, HMF and OBMF with different Activated Methylene Group compounds, using for the first‐time dimethyl carbonate as the reaction media. Most of the resulting products were isolated as pure via simple liquid‐liquid extraction in good to excellent yields. Future applications of these compounds might include aldoxime reduction into amine furanics ‐ herein also preliminary investigated ‐ and hydrolysis of the nitrile derivatives in the related carboxylic acid (or ester) furanics. All these products are interesting monomers for the preparation of bio‐based polymers.

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Mustard Carbonate Analogues as Sustainable Reagents for the Aminoalkylation of Phenols

Abstract: Figure 1. Structure and reactivity of mustard gas versus ß-aminocarbonates.

Cited by 5 publications

References 58 publications

Microwave-Assisted Aminoalkylation of Phenols via Mustard Carbonate Analogues

Microwave-Assisted Aminoalkylation of Phenols via Mustard Carbonate Analogues

Reaction Pathways in Carbonates and Esters

Nitrile Furanics via Copper‐Catalyzed Dehydration of Aldoximes and Knoevenagel Condensation

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