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Synthesis 2023; 55(07): 1130-1138
DOI: 10.1055/a-1970-8229
paper

Practical One-Pot Synthesis of 4,6-Bis(hetero)aryl- and 4-(Hetero) aryl-6-methyl-substituted 1,3,5-Triazin-2-amines

Laís C. Calheiros
a   Grupo de Pesquisa em Síntese e Caracterização Molecular do Mato Grosso do Sul, Universidade Federal da Grande Dourados, 79825-070 Dourados (MS), Brazil
b   Laboratorio de Síntese de Substâncias Bioativas, CINPROBIO-CLF, Universidade Federal da Grande Dourados, 79825-070 Dourados (MS), Brazil
,
Sidnei Moura
c   Laboratório de Biotecnologia de Produtos Naturais e Sintéticos, Universidade de Caxias do Sul, 95070-560 Caxias do Sul (RS), Brazil
,
Davi F. Back
d   Laboratório de Materiais Inorgânicos, Universidade Federal de Santa Maria, 97105-900 Santa Maria (RS), Brazil
,
Guilherme C. Paveglio∗
a   Grupo de Pesquisa em Síntese e Caracterização Molecular do Mato Grosso do Sul, Universidade Federal da Grande Dourados, 79825-070 Dourados (MS), Brazil
b   Laboratorio de Síntese de Substâncias Bioativas, CINPROBIO-CLF, Universidade Federal da Grande Dourados, 79825-070 Dourados (MS), Brazil
,
Gleison A. Casagrande∗
e   Grupo de Pesquisa em Síntese e Caracterização Molecular do Mato Grosso do Sul, Universidade Federal de Mato Grosso do Sul, 79074-460 Campo Grande (MS), Brazil
,
Lucas Pizzuti  ∗
a   Grupo de Pesquisa em Síntese e Caracterização Molecular do Mato Grosso do Sul, Universidade Federal da Grande Dourados, 79825-070 Dourados (MS), Brazil
b   Laboratorio de Síntese de Substâncias Bioativas, CINPROBIO-CLF, Universidade Federal da Grande Dourados, 79825-070 Dourados (MS), Brazil
› Author AffiliationsThis work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant number 435178/2018-0), Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (Fundect, grant number 71/027.195/2022), and Financiadora de Estudos e Projetos (MCTI/Finep/CT-Infra – 01/2013, grant number 04.13.0448.00; MCTI/Finep/CT-Infra-Proinfra – 02/2014, grant number 04.18.0011.00).
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Abstract

Two series of 4,6-disubstituted 1,3,5-triazin-2-amines were prepared by cesium carbonate-promoted cotrimerization of aromatic nitriles with guanidine and the reaction of (hetero)aryl nitriles with N-acetylguanidine. The first series of 4,6-bis(hetero)aryl-1,3,5-triazin-2-amines was synthesized in yields of 56–85% by adapting a traditional approach that starts from readily available substrates but requires strong and hard-to-handle bases as well as presents serious scope limitations. In this line, the method developed here used a mild base and overcame the scope limitation for p-substituted benzonitrile with electron-releasing group. The second series of 4-(hetero)aryl-6-methyl-1,3,5-triazin-2-amines comprises unsymmetrically substituted symmetrical triazines, which were synthesized in yields of 58–75%. In summary, this work highlighted a synthetic method, which tolerates broad range of substrates, including o- and p-substituted benzonitriles as well as heteroaromatic nitriles.

Key words

symmetrical triazines - heterocycles - cotrimerization reactions - guanidine - cesium carbonate

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1970-8229.
  • Supporting Information


Publication History

Received: 21 September 2022

Accepted after revision: 02 November 2022

Accepted Manuscript online:
02 November 2022

Article published online:
06 December 2022

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