- Trialkylammonium salt degradation: Implications for methylation and cross-coupling
-
Trialkylammonium (most notably 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 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. New mechanistic insights have enabled the investigation of the use of trimethylanilinium salts in O-methylation and in improved cross-coupling strategies. Finally, detailed computational studies have helped highlight limitations in the current state-of-the-art of solvation modelling of reaction in which the bulk medium undergoes experimentally observable changes over the reaction timecourse. This journal is
- Assante, Michele,Baillie, Sharon E.,Juba, Vanessa,Leach, Andrew G.,McKinney, David,Reid, Marc,Washington, Jack B.,Yan, Chunhui
-
p. 6949 - 6963
(2021/06/02)
-
- Direct trifluoro-methoxylation of aromatics with perfluoro-methyl- hypofluorite
-
The reactivity of CF3OF (FTM) has been widely studied especially in halogenated olefinic systems and its use in pharmaceutical synthesis as a mild radical and electrophilic fluorinating agent is well documented. On the other hand, the chemical behavior of the perfluoro-methyl-hypofluorite with aromatic substrates is much less studied. Up to now few and scattered data regarding its use as electrophilic fluorinating agent of variously substituted aromatic compounds are found in the literature. In this work the reactivity of CF3OF with simple electron rich and electron poor aromatics (α,α,α-trifluoro-toluene, toluene, benzene, chloro-benzene, methoxybenzene) has been investigated. The possibility of selectively bind the trifluoro-methoxy group (via radical mechanism) or the fluorine atom (via electrophilic addition) by varying the reaction conditions has been explored. In particular we have observed that the trifluoro-methoxy free radical substitution can be the main synthetic pathway if the reaction is promoted by an independent and steady source of CF3O radical.
- Venturini, Francesco,Navarrini, Walter,Famulari, Antonino,Sansotera, Maurizio,Dardani, Patrizia,Tortelli, Vito
-
experimental part
p. 43 - 48
(2012/08/14)
-
- Silver-mediated trifluoromethoxylation of aryl stannanes and arylboronic acids
-
A silver-mediated cross-coupling of trifluoromethoxide with aryl stannanes and arylboronic acids to give aryl trifluoromethyl ethers is reported. This is the first report of a transition-metal-mediated Caryl-OCF3 bond formation.
- Huang, Chenghong,Liang, Theresa,Harada, Shinji,Lee, Eunsung,Ritter, Tobias
-
supporting information; experimental part
p. 13308 - 13310
(2011/10/10)
-
- Lability of the trifluoromethyl group of trifluoromethoxybenzenes under HF/Lewis acid conditions
-
The trifluoromethyl functionality of trifluoromethoxybenzenes (trifluoromethyl phenyl ethers) becomes labile under HF/Lewis acid conditions. Substrates with an unsubstituted para-position shed their -CF3 groups while performing a Friedel-Crafts reaction upon another substrate molecule's trifluoromethoxy group to generate p-rosolic acids. Substrates that had blocking groups at the para-positions reacted ortho. The electron donating substituents methoxy and phenoxy interfered with the formation of rosolic acids.
- Belter, Randolph K.
-
scheme or table
p. 1302 - 1307
(2011/02/22)
-
- CF3 oxonium salts, O-(trifluoromethyl)dibenzofuranium salts: In situ synthesis, properties, and application as a real CF3+ species reagent
-
(Chemical Equation Presented) We report in situ synthesis of the first CF3 oxonium salts, thermally unstable O-(trifluoromethyl)- dibenzofuranium salts, which furthermore have different counteranions (BF 4-, PF6-, SbF6 -, and Sb2F11-) and ring substituents (tert-butyl, F, and OCH3), by photochemical decomposition of the corresponding 2-(trifluoromethoxy)biphenylyl-2′- diazonium salts at -90 to -100°C. The yields markedly increased in the order of BF4- 6- 6- 2F11-. The CF3 oxonium salts were fully assigned by means of 1H and 19F NMR spectroscopy at low temperature. The CF3 salts decomposed to form CF4 and dibenzofurans. The half-life times at -60°C of the 2-tert-butyl salts having different counteranions were 29 min for BF4- salt 2d, 36 min for PF6- salt 2c, 270 min for SbF6- salt 2a, and 415 min for Sb2F11- salt 2b. Those at -60°C of the Sb2F11- salts having different 2-substituents were 13 min for F salt 3b, 63 min for H (unsubstituted) salt 1b, and 415 min for tert-butyl salt 2b. Thus, the stability of the CF3 oxonium salts increased in the order of BF4- 6 - 6- 2F 11- and F 3+ species source to the direct O- and N-trifluoromethylations of alcohols, phenols, amines, anilines, and pyridines under very mild conditions. The thermal decomposition method with a mixture of diazonium salt 17a and aryl- or alkylsulfonic acids, pyridine, or pyridines having an electron-withdrawing group also afforded CF3O or CF 3N products. The trifluoromethylation mechanism is discussed and an SN2 mechanism containing the transient formation of free CF 3+ is proposed. Thus, the present study has demonstrated that the exceedingly reactive CF3+ species can be generated much easier than the CH3+ species, contrary to the common sense that CF3+ is extremely difficult to generate in solution.
- Umemoto, Teruo,Adachi, Kenji,Ishihara, Sumi
-
p. 6905 - 6917
(2008/02/11)
-
- Pharmaceutical uses for fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles
-
The present invention relates to methods of treating various CNS and other disorders by adminstering fluoroalkoxybenzylamino derivatives of nitrogen containing heterocyclic compounds, and specifically, by administering compounds of the formula wherein Q,
- -
-
-
- Fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles
-
The present invention relates to novel fluoroalkoxybenzylamino derivatives of nitrogen containing heterocyclic compounds, and specifically, to compounds of the formula STR1 wherein Q, X1, X2 and X3 are as defined below. Th
- -
-
-
- FLUOROALKOXYBENZYLAMINO DERIVATIVES OF NITROGEN CONTAINING HETEROCYCLES
-
The present invention relates to novel fluoroalkoxybenzylamino derivatives of nitrogen containing heterocyclic compounds, and specifically, to compounds of the formula STR1 wherein Q, X 1, x. sup.2 and X 3 are as defined below. These novel compounds are u
- -
-
-
