Aromatic Substitution Reactions of Amines with Ring-Substituted 1-Phenyl-2, 2, 2-trifluoroethyl Carbocations

John P. Richard

doi:10.1021/ja00199a037

Aromatic Substitution Reactions of Amines with Ring-Substituted 1-Phenyl-2, 2, 2-trifluoroethyl Carbocations

John P. Richard

Chemistry

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Abstract

4-MeOArCH(CFi)Br in 20% acetonitrile in water reacts with Me, NH to form 4-MeOArCH(CF₃)NMe₂ and 4-Me₂NArCH(CF₃)NMe₂, with MeO(CH₂)₂NH₂ to form 4-MeOArCH(CF₃)NH(CH₂)₂OMe and 4-MeO-(CH₂)₂NHArCH(CF₃)NH(CH₂)₂OMe, and with a mixture of MeO(CH₂)₂NH₂ and Me₂NH to form all the above-mentioned products plus 4-Me₂NArCH(CF₃)NH(CH₂)₂OMe and 4-MeO(CH₂)₂NHArCH(CF₃)NMe₂. Evidence is presented that the aromatic substitution products of these reactions are formed by a four-step mechanism through the following three reaction intermediates. (1) 4-MeOArCH(CF₃)⁺: 4-MeOArCH(CF₃)Br ionizes to 4-MeOArCH(CF₃)⁺, which is trapped by azide ion and solvent with a partition rate constant ratio of k_az/k_s= 50 M⁻¹. 4-Me₂NArCH(CF₃)NMe₂ is formed by a mechanism that includes Me₂NH capture of 4-MeOArCH(CF₃)⁺as a step, rather than by direct addition of Me₂NH to 4MeOArCH(CF₃)Br. (2) C-4 amine adduct to 4-MeOArCH(CF₃)⁺: The carbocation 4-MeOArCH(CF₃)⁺undergoes aromatic substitution by amines to form 4-R₁R₂NArCH(CF₃)⁺. By analogy with the mechanisms for related aromatic substitution reactions, it is proposed that the C-4 amine adduct to 4-MeOArCH(CF₃)⁺is an intermediate of this reaction. (3) 4-R₁R₂NArCH(CF₃)⁺: The reaction of 4-MeOArCH(CF₃)Br with Me₂NH and N₃~ gives 4-Me₂NArCH(CF₃)N₃ from the capture of 4-Me₂NArCH(CF₃)⁺by N₃⁻. The same product ratio 4-Me₂NArCH(CF₃)NMe₂/4-Me₂NArCH(CF₃)N₃ is observed from the reaction of 4-MeOArCH(CF₃)Br, 4-MeOArCH(CF₃)Tos, and 4-Me₂NArCH(CF₃)(3, 5-dinitrobenzoate) at a number of [Me₂NH]/[N₃⁻] ratios. This is classical evidence that each compound reacts through 4-Me₂NArCH(CF₃)⁺, which has been shown to form as an intermediate of the solvolysis reaction of 4-Me₂NArCH(CF₃)(3, 5-dinitrobenzoate).^5b The reaction of 4-MeOArCH(CF₃)⁺in the presence of MeO(CH₂)₂NH₂ gives 4-MeO(CH₂)₂NHArCH(CF₃)⁺, which is trapped by Me₂NH and MeO(CH₂)₂NH₂ with the same rate constant ratio observed for the trapping of the intermediate generated in the S_N1 reaction of 4-MeO-(CH₂)₂NHArCH(CF₃)N₃. The reaction of 4-MeSArCH(CF₃)Br in the presence of Me₂NH gives 4-Me₂NArCH(CF₃)NMe₂, presumably by a mechanism similar to that for the reaction of 4-MeOArCH(CF₃)Br in the presence of Me₂NH. Factors that favor nucleophilic aromatic substitution reactions at a-benzyl carbocations are discussed.

Original language	English
Pages (from-to)	6735-6744
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	111
Issue number	17
DOIs	https://doi.org/10.1021/ja00199a037
State	Published - Aug 1 1989

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@article{e48b39d320d54e4d873d81f33ee080f4,

title = "Aromatic Substitution Reactions of Amines with Ring-Substituted 1-Phenyl-2, 2, 2-trifluoroethyl Carbocations",

abstract = "4-MeOArCH(CFi)Br in 20\% acetonitrile in water reacts with Me, NH to form 4-MeOArCH(CF3)NMe2 and 4-Me2NArCH(CF3)NMe2, with MeO(CH2)2NH2 to form 4-MeOArCH(CF3)NH(CH2)2OMe and 4-MeO-(CH2)2NHArCH(CF3)NH(CH2)2OMe, and with a mixture of MeO(CH2)2NH2 and Me2NH to form all the above-mentioned products plus 4-Me2NArCH(CF3)NH(CH2)2OMe and 4-MeO(CH2)2NHArCH(CF3)NMe2. Evidence is presented that the aromatic substitution products of these reactions are formed by a four-step mechanism through the following three reaction intermediates. (1) 4-MeOArCH(CF3)+: 4-MeOArCH(CF3)Br ionizes to 4-MeOArCH(CF3)+, which is trapped by azide ion and solvent with a partition rate constant ratio of kaz/ks= 50 M−1. 4-Me2NArCH(CF3)NMe2 is formed by a mechanism that includes Me2NH capture of 4-MeOArCH(CF3)+as a step, rather than by direct addition of Me2NH to 4MeOArCH(CF3)Br. (2) C-4 amine adduct to 4-MeOArCH(CF3)+: The carbocation 4-MeOArCH(CF3)+undergoes aromatic substitution by amines to form 4-R1R2NArCH(CF3)+. By analogy with the mechanisms for related aromatic substitution reactions, it is proposed that the C-4 amine adduct to 4-MeOArCH(CF3)+is an intermediate of this reaction. (3) 4-R1R2NArCH(CF3)+: The reaction of 4-MeOArCH(CF3)Br with Me2NH and N3\textasciitilde{} gives 4-Me2NArCH(CF3)N3 from the capture of 4-Me2NArCH(CF3)+by N3−. The same product ratio 4-Me2NArCH(CF3)NMe2/4-Me2NArCH(CF3)N3 is observed from the reaction of 4-MeOArCH(CF3)Br, 4-MeOArCH(CF3)Tos, and 4-Me2NArCH(CF3)(3, 5-dinitrobenzoate) at a number of [Me2NH]/[N3−] ratios. This is classical evidence that each compound reacts through 4-Me2NArCH(CF3)+, which has been shown to form as an intermediate of the solvolysis reaction of 4-Me2NArCH(CF3)(3, 5-dinitrobenzoate).5b The reaction of 4-MeOArCH(CF3)+in the presence of MeO(CH2)2NH2 gives 4-MeO(CH2)2NHArCH(CF3)+, which is trapped by Me2NH and MeO(CH2)2NH2 with the same rate constant ratio observed for the trapping of the intermediate generated in the SN1 reaction of 4-MeO-(CH2)2NHArCH(CF3)N3. The reaction of 4-MeSArCH(CF3)Br in the presence of Me2NH gives 4-Me2NArCH(CF3)NMe2, presumably by a mechanism similar to that for the reaction of 4-MeOArCH(CF3)Br in the presence of Me2NH. Factors that favor nucleophilic aromatic substitution reactions at a-benzyl carbocations are discussed.",

author = "Richard, \{John P.\}",

year = "1989",

month = aug,

day = "1",

doi = "10.1021/ja00199a037",

language = "English",

volume = "111",

pages = "6735--6744",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "17",

}

TY - JOUR

T1 - Aromatic Substitution Reactions of Amines with Ring-Substituted 1-Phenyl-2, 2, 2-trifluoroethyl Carbocations

AU - Richard, John P.

PY - 1989/8/1

Y1 - 1989/8/1

N2 - 4-MeOArCH(CFi)Br in 20% acetonitrile in water reacts with Me, NH to form 4-MeOArCH(CF3)NMe2 and 4-Me2NArCH(CF3)NMe2, with MeO(CH2)2NH2 to form 4-MeOArCH(CF3)NH(CH2)2OMe and 4-MeO-(CH2)2NHArCH(CF3)NH(CH2)2OMe, and with a mixture of MeO(CH2)2NH2 and Me2NH to form all the above-mentioned products plus 4-Me2NArCH(CF3)NH(CH2)2OMe and 4-MeO(CH2)2NHArCH(CF3)NMe2. Evidence is presented that the aromatic substitution products of these reactions are formed by a four-step mechanism through the following three reaction intermediates. (1) 4-MeOArCH(CF3)+: 4-MeOArCH(CF3)Br ionizes to 4-MeOArCH(CF3)+, which is trapped by azide ion and solvent with a partition rate constant ratio of kaz/ks= 50 M−1. 4-Me2NArCH(CF3)NMe2 is formed by a mechanism that includes Me2NH capture of 4-MeOArCH(CF3)+as a step, rather than by direct addition of Me2NH to 4MeOArCH(CF3)Br. (2) C-4 amine adduct to 4-MeOArCH(CF3)+: The carbocation 4-MeOArCH(CF3)+undergoes aromatic substitution by amines to form 4-R1R2NArCH(CF3)+. By analogy with the mechanisms for related aromatic substitution reactions, it is proposed that the C-4 amine adduct to 4-MeOArCH(CF3)+is an intermediate of this reaction. (3) 4-R1R2NArCH(CF3)+: The reaction of 4-MeOArCH(CF3)Br with Me2NH and N3~ gives 4-Me2NArCH(CF3)N3 from the capture of 4-Me2NArCH(CF3)+by N3−. The same product ratio 4-Me2NArCH(CF3)NMe2/4-Me2NArCH(CF3)N3 is observed from the reaction of 4-MeOArCH(CF3)Br, 4-MeOArCH(CF3)Tos, and 4-Me2NArCH(CF3)(3, 5-dinitrobenzoate) at a number of [Me2NH]/[N3−] ratios. This is classical evidence that each compound reacts through 4-Me2NArCH(CF3)+, which has been shown to form as an intermediate of the solvolysis reaction of 4-Me2NArCH(CF3)(3, 5-dinitrobenzoate).5b The reaction of 4-MeOArCH(CF3)+in the presence of MeO(CH2)2NH2 gives 4-MeO(CH2)2NHArCH(CF3)+, which is trapped by Me2NH and MeO(CH2)2NH2 with the same rate constant ratio observed for the trapping of the intermediate generated in the SN1 reaction of 4-MeO-(CH2)2NHArCH(CF3)N3. The reaction of 4-MeSArCH(CF3)Br in the presence of Me2NH gives 4-Me2NArCH(CF3)NMe2, presumably by a mechanism similar to that for the reaction of 4-MeOArCH(CF3)Br in the presence of Me2NH. Factors that favor nucleophilic aromatic substitution reactions at a-benzyl carbocations are discussed.

AB - 4-MeOArCH(CFi)Br in 20% acetonitrile in water reacts with Me, NH to form 4-MeOArCH(CF3)NMe2 and 4-Me2NArCH(CF3)NMe2, with MeO(CH2)2NH2 to form 4-MeOArCH(CF3)NH(CH2)2OMe and 4-MeO-(CH2)2NHArCH(CF3)NH(CH2)2OMe, and with a mixture of MeO(CH2)2NH2 and Me2NH to form all the above-mentioned products plus 4-Me2NArCH(CF3)NH(CH2)2OMe and 4-MeO(CH2)2NHArCH(CF3)NMe2. Evidence is presented that the aromatic substitution products of these reactions are formed by a four-step mechanism through the following three reaction intermediates. (1) 4-MeOArCH(CF3)+: 4-MeOArCH(CF3)Br ionizes to 4-MeOArCH(CF3)+, which is trapped by azide ion and solvent with a partition rate constant ratio of kaz/ks= 50 M−1. 4-Me2NArCH(CF3)NMe2 is formed by a mechanism that includes Me2NH capture of 4-MeOArCH(CF3)+as a step, rather than by direct addition of Me2NH to 4MeOArCH(CF3)Br. (2) C-4 amine adduct to 4-MeOArCH(CF3)+: The carbocation 4-MeOArCH(CF3)+undergoes aromatic substitution by amines to form 4-R1R2NArCH(CF3)+. By analogy with the mechanisms for related aromatic substitution reactions, it is proposed that the C-4 amine adduct to 4-MeOArCH(CF3)+is an intermediate of this reaction. (3) 4-R1R2NArCH(CF3)+: The reaction of 4-MeOArCH(CF3)Br with Me2NH and N3~ gives 4-Me2NArCH(CF3)N3 from the capture of 4-Me2NArCH(CF3)+by N3−. The same product ratio 4-Me2NArCH(CF3)NMe2/4-Me2NArCH(CF3)N3 is observed from the reaction of 4-MeOArCH(CF3)Br, 4-MeOArCH(CF3)Tos, and 4-Me2NArCH(CF3)(3, 5-dinitrobenzoate) at a number of [Me2NH]/[N3−] ratios. This is classical evidence that each compound reacts through 4-Me2NArCH(CF3)+, which has been shown to form as an intermediate of the solvolysis reaction of 4-Me2NArCH(CF3)(3, 5-dinitrobenzoate).5b The reaction of 4-MeOArCH(CF3)+in the presence of MeO(CH2)2NH2 gives 4-MeO(CH2)2NHArCH(CF3)+, which is trapped by Me2NH and MeO(CH2)2NH2 with the same rate constant ratio observed for the trapping of the intermediate generated in the SN1 reaction of 4-MeO-(CH2)2NHArCH(CF3)N3. The reaction of 4-MeSArCH(CF3)Br in the presence of Me2NH gives 4-Me2NArCH(CF3)NMe2, presumably by a mechanism similar to that for the reaction of 4-MeOArCH(CF3)Br in the presence of Me2NH. Factors that favor nucleophilic aromatic substitution reactions at a-benzyl carbocations are discussed.

UR - https://www.scopus.com/pages/publications/0347826718

U2 - 10.1021/ja00199a037

DO - 10.1021/ja00199a037

M3 - Article

AN - SCOPUS:0347826718

SN - 0002-7863

VL - 111

SP - 6735

EP - 6744

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 17

ER -

Aromatic Substitution Reactions of Amines with Ring-Substituted 1-Phenyl-2, 2, 2-trifluoroethyl Carbocations

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