A comparison of several modern alkylating agents

Lamoureux, Guy; Agüero, Christian

doi:10.3998/ark.5550190.0010.108

Cited by 89 publications

(43 citation statements)

References 23 publications

(22 reference statements)

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“…40 Parallel to drug design, formal access to highly toxic electrophilic methyl halide reagents in situ via anilinium salts may provide safer alternatives to more widely known carcinogenic and low-boiling methylating reagents. 42 Of the various classes of methylating reagent available, [43][44][45][46] electrophilic sources still represent a signicant tool for synthetic chemists (Fig. 2).…”

Section: Drivers Towards Understanding the Methylating Ability Of Anilinium Saltsmentioning

confidence: 99%

Trialkylammonium salt degradation: implications for methylation and cross-coupling

et al. 2021

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Section: Drivers Towards Understanding the Methylating Ability Of Anilinium Saltsmentioning

confidence: 99%

Trialkylammonium salt degradation: implications for methylation and cross-coupling

et al. 2021

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“…37 Parallel to drug design, formal access to highly toxic electrophilic methyl halide reagents in situ via anilinium salts may provide safer alternatives to more widely known methylating reagents. 39 Of the various classes of methylating reagent available, [40][41][42][43] electrophilic sources still represent a significant tool for synthetic chemists (Figure 2). As with all reagents, toxicity, safety, scalability, and operational difficulty play a key role in the decision to use or replace said reagent.…”

Section: Drivers Towards Understanding the Methylating Ability Of Anilinium Saltsmentioning

confidence: 99%

A Mechanistic Analysis of Trimethylanilinium Salt Degradation: Implications for Methylation and Cross-coupling Applications

Washington¹,

Assante²,

Yan³

et al. 2021

Preprint

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N,N,N-trimethylanilinium salts are known to display dual reactivity through both the aryl group and the N-methyl groups. These salts have thus been widely applied in cross-coupling, aryl etherification, fluorine radiolabelling, phase-transfer catalysis, supramolecular recognition, polymer design, and (more recently) methylation. However, their application as electrophilic methylating reagents remains somewhat underexplored, and an understanding of their arylation versus methylation reactivities is lacking. This study presents a mechanistic degradation analysis of N,N,N-trimethylanilinium salts and highlights the implications for synthetic applications of this important class of salts. Kinetic degradation studies, in both solid state and solution phases, have delivered insights into the physical and chemical parameters affecting anilinium salt stability. 1H NMR kinetic analysis of salt degradation has evidenced thermal degradation to methyl iodide and the parent aniline, consistent with a closed-shell SN2-centred degradative pathway, and methyl iodide being the key reactive species in applied methylation procedures. Furthermore, the effect of halide and non-nucleophilic counterions on salt degradation has been investigated, along with deuterium isotope and solvent effects. Finally, new mechanistic insights have enabled the investigation of the use of trimethylanilinium salts in O-methylation and in improved cross-coupling strategies.

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“…DACs display only low (eco)toxicity and are completely biodegradable. In particular, DMC is classified as a flammable liquid that does not smell (methanol-like odor) and does not have irritating or mutagenic effects by either contact or inhalation (Lamoureux and Agüero, 2009). As a result, DMC is a safe to handle compound and a very efficient alternative to chlorine reagents, as it can replace toxic methyl halides and dimethyl sulfate in alkylation reactions and phosgene in alkoxycarbonylation reactions.…”

Section: Introductionmentioning

confidence: 99%

Dialkyl Carbonates in the Green Synthesis of Heterocycles

2019

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This review focuses on the use of dialkyl carbonates (DACs) as green reagents and solvents for the synthesis of several 5- and 6-membered heterocycles including: tetrahydrofuran and furan systems, pyrrolidines, indolines, isoindolines, 1,4-dioxanes, piperidines, and cyclic carbamates. Depending on the heterocycle investigated, the synthetic approach used was different. Tetrahydrofuran systems, pyrrolidines, indolines, isoindoline, and 1,4-dioxanes were synthesized using dimethyl carbonate (DMC) as sacrificial molecule (B Ac 2/B Al 2 mechanism). Cyclic carbamates, namely 1,3-oxazin-2-ones, were prepared employing DACs as carbonylating agents, either by B Ac 2/B Al 2 mechanism or through a double B Ac 2 mechanism. Piperidines were synthetized taking advantage of the anchimeric effect of a new family of dialkyl carbonates, i.e., mustard carbonates. Finally, in the case 5-hydroxymethylfurfural (HMF), DMC has been employed as efficient extracting solvent of this extensively investigated bio-based platform chemical from the reaction mixture. These synthetic approaches demonstrate, once again, the great versatility of DACs and their—yet to be fully explored—potential as green reagents and solvents in the synthesis of heterocycles.

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A comparison of several modern alkylating agents

Cited by 89 publications

References 23 publications

Trialkylammonium salt degradation: implications for methylation and cross-coupling

Trialkylammonium salt degradation: implications for methylation and cross-coupling

A Mechanistic Analysis of Trimethylanilinium Salt Degradation: Implications for Methylation and Cross-coupling Applications

Dialkyl Carbonates in the Green Synthesis of Heterocycles

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