Four mechanisms in the reactions of 3-aminopyrrole with 1,3,5-triazines: Inverse electron demand diels-alder cycloadditions vs SNAr reactions via uncatalyzed and acid-catalyzed pathways

Michael De Rosa, David Arnold, Douglas Hartline

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12 Citations (Scopus)

Abstract

Reaction of 3-aminopyrrole with seven 1,3,5-triazines was studied in a one-step reaction (in situ formation of 3-aminopyrrole) and a two-step reaction (using the tetraphenylborate salt and an amine base). An inverse-electron demand Diels-Alder reaction (IEDDA) was observed with R1 = CF3, CO2Et, and H with the formation of 5H-pyrrolo[3,2-d]pyrimidine derivatives. SNAr was observed when 2,4,6-trifluoro- or 2,4,6-trichloro-1,3,5-triazine were used - 1,3,5-triazines that had leaving groups. If excess 1,3,5-triazine was present the initial SNAr product reacted further, in the presence of acid and water, with another equivalent of 1,3,5-triazine to give compounds containing three linked heterocyclic rings. No reaction was observed with R1 = C6H5 and OCH3. Four mechanisms are proposed to explain the experimental results: uncatalyzed and acid catalyzed inverse electron demand Diels-Alder cascades leading to cycloaddition, and uncatalyzed and acid-catalyzed S NAr reactions leading, respectively, to single and double substitution products. Acid catalysis was a factor when there was reduced reactivity in either reactant.

Original languageEnglish (US)
Pages (from-to)8614-8623
Number of pages10
JournalJournal of Organic Chemistry
Volume78
Issue number17
DOIs
StatePublished - Sep 6 2013

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Triazines
Cycloaddition
Acids
Electrons
Tetraphenylborate
Catalysis
Amines
Substitution reactions
Salts
Derivatives
Water

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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title = "Four mechanisms in the reactions of 3-aminopyrrole with 1,3,5-triazines: Inverse electron demand diels-alder cycloadditions vs SNAr reactions via uncatalyzed and acid-catalyzed pathways",
abstract = "Reaction of 3-aminopyrrole with seven 1,3,5-triazines was studied in a one-step reaction (in situ formation of 3-aminopyrrole) and a two-step reaction (using the tetraphenylborate salt and an amine base). An inverse-electron demand Diels-Alder reaction (IEDDA) was observed with R1 = CF3, CO2Et, and H with the formation of 5H-pyrrolo[3,2-d]pyrimidine derivatives. SNAr was observed when 2,4,6-trifluoro- or 2,4,6-trichloro-1,3,5-triazine were used - 1,3,5-triazines that had leaving groups. If excess 1,3,5-triazine was present the initial SNAr product reacted further, in the presence of acid and water, with another equivalent of 1,3,5-triazine to give compounds containing three linked heterocyclic rings. No reaction was observed with R1 = C6H5 and OCH3. Four mechanisms are proposed to explain the experimental results: uncatalyzed and acid catalyzed inverse electron demand Diels-Alder cascades leading to cycloaddition, and uncatalyzed and acid-catalyzed S NAr reactions leading, respectively, to single and double substitution products. Acid catalysis was a factor when there was reduced reactivity in either reactant.",
author = "{De Rosa}, Michael and David Arnold and Douglas Hartline",
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T1 - Four mechanisms in the reactions of 3-aminopyrrole with 1,3,5-triazines

T2 - Inverse electron demand diels-alder cycloadditions vs SNAr reactions via uncatalyzed and acid-catalyzed pathways

AU - De Rosa, Michael

AU - Arnold, David

AU - Hartline, Douglas

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N2 - Reaction of 3-aminopyrrole with seven 1,3,5-triazines was studied in a one-step reaction (in situ formation of 3-aminopyrrole) and a two-step reaction (using the tetraphenylborate salt and an amine base). An inverse-electron demand Diels-Alder reaction (IEDDA) was observed with R1 = CF3, CO2Et, and H with the formation of 5H-pyrrolo[3,2-d]pyrimidine derivatives. SNAr was observed when 2,4,6-trifluoro- or 2,4,6-trichloro-1,3,5-triazine were used - 1,3,5-triazines that had leaving groups. If excess 1,3,5-triazine was present the initial SNAr product reacted further, in the presence of acid and water, with another equivalent of 1,3,5-triazine to give compounds containing three linked heterocyclic rings. No reaction was observed with R1 = C6H5 and OCH3. Four mechanisms are proposed to explain the experimental results: uncatalyzed and acid catalyzed inverse electron demand Diels-Alder cascades leading to cycloaddition, and uncatalyzed and acid-catalyzed S NAr reactions leading, respectively, to single and double substitution products. Acid catalysis was a factor when there was reduced reactivity in either reactant.

AB - Reaction of 3-aminopyrrole with seven 1,3,5-triazines was studied in a one-step reaction (in situ formation of 3-aminopyrrole) and a two-step reaction (using the tetraphenylborate salt and an amine base). An inverse-electron demand Diels-Alder reaction (IEDDA) was observed with R1 = CF3, CO2Et, and H with the formation of 5H-pyrrolo[3,2-d]pyrimidine derivatives. SNAr was observed when 2,4,6-trifluoro- or 2,4,6-trichloro-1,3,5-triazine were used - 1,3,5-triazines that had leaving groups. If excess 1,3,5-triazine was present the initial SNAr product reacted further, in the presence of acid and water, with another equivalent of 1,3,5-triazine to give compounds containing three linked heterocyclic rings. No reaction was observed with R1 = C6H5 and OCH3. Four mechanisms are proposed to explain the experimental results: uncatalyzed and acid catalyzed inverse electron demand Diels-Alder cascades leading to cycloaddition, and uncatalyzed and acid-catalyzed S NAr reactions leading, respectively, to single and double substitution products. Acid catalysis was a factor when there was reduced reactivity in either reactant.

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