Unexpected Highly Chemoselective Nucleophilic Substitution Reaction of 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline with Various Nucleophiles

Okada, Etsuji; Hatakenaka, Mizuki; Keisuke, Iwakuni

doi:10.3987/com-15-s(t)54

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…The key step on the above studies is a unique aromatic nucleophilic substitution of 4-dimethylamino moiety of trifluoroacetylated quinoline 1 with N-, S-, and O-nucleophiles (Scheme 1). 8 Previously, we reported highly selective nucleophilic substitutions on 4-(dimethylamino)-2-methoxy-3-(trifluoroacetyl)quinoline 2 giving 3 9,10 together with some computational studies on their reaction course. [11][12][13] Here we wish to describe the DFT calculation (RB3LYP/6-31G*) study on the reaction of 1 as the more simplified substrate than 2 bearing electron donative methoxy group at the 2-position in order to elucidate the essential reactivity of 3-trifluoroacetylquinoline system with various nucleophiles.…”

Section: Introductionmentioning

confidence: 99%

Computational Study for the Aromatic Nucleophilic Substitution of 4-Dimethylamino-3-trifluoroacetyl- quinoline with Various Nucleophiles

Okada¹,

Ota²,

Nakagawa³

et al. 2021

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The aromatic nucleophilic substitutions of 4-dimethylamino-3-trifluoroacetylquinoline 1 with amines, thiols, and alcohols are elucidated on the basis of DFT calculations. Our calculation results suggest that the reaction of 1 with amines giving N-N exchanged products 4 occurs via Meisenheimer type adducts V whereas the ones with thiols and alcohols proceed via the enol type adducts VII and IX to afford N-S and N-O exchanged products 8 and 9, respectively. It is also clarified that the conditions required for the successful substitution are not controlled by the activation energies on these processes, but by the energy changes on the processes from 1 to each intermediates, V, VII, and IX.

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Section: Introductionmentioning

confidence: 99%

Computational Study for the Aromatic Nucleophilic Substitution of 4-Dimethylamino-3-trifluoroacetyl- quinoline with Various Nucleophiles

Okada¹,

Ota²,

Nakagawa³

et al. 2021

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“…7 The key step reaction on the above studies is a unique highly selective aromatic nucleophilic substitution of 4-dimethylamino moiety of trifluoroacetylated quinoline 1 with appropriate nucleophiles (Scheme 1). 7,8 It is impressive that the nucleophilic substitution of 1 with alcohols are easily performed at its 4-position exclusively by simple alcoholysis to…”

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confidence: 99%

Selective Aromatic Nucleophilic Substitution of 4-(Dimethylamino)-2-methoxy-3-(trifluoroacetyl)quinoline with Thiols – DFT Calculation Study

Okada¹,

Ota²,

Harada³

et al. 2019

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The nucleophilic aromatic substitution proceeds exclusively at the 4-position of 4-dimethylamino-2-methoxy-3-(trifluoroacetyl)quinoline 1 by simple alcoholysis to give the corresponding NO exchanged products solely, and no O-O exchange reactions at the 2-position are performed. Our DFT calculation study provides a rational explanation regarding this complete selectivity based on relative energies of the intermediates VII, VIII which are corresponding to the O-protonated Meisenheimer complexes at carbonyl oxygen in 3-trifluoroacetyl group. The reaction pathway for the present unique selective substitution with alcohols is elucidated by referring to the analogous selective substitutions on 1 with amines and thiols as nucleophiles.

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Computational Study for the Selective Aromatic Nucleophilic Substitution on 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline

Okada¹,

Ota²,

Sasakawa³

et al. 2018

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Unexpected Highly Chemoselective Nucleophilic Substitution Reaction of 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline with Various Nucleophiles

Cited by 4 publications

References 26 publications

Computational Study for the Aromatic Nucleophilic Substitution of 4-Dimethylamino-3-trifluoroacetyl- quinoline with Various Nucleophiles

Computational Study for the Aromatic Nucleophilic Substitution of 4-Dimethylamino-3-trifluoroacetyl- quinoline with Various Nucleophiles

Selective Aromatic Nucleophilic Substitution of 4-(Dimethylamino)-2-methoxy-3-(trifluoroacetyl)quinoline with Thiols – DFT Calculation Study

Computational Study for the Selective Aromatic Nucleophilic Substitution on 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline

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