Synthesis of Heterocyclic Compounds with Pyrimidine-4-carbaldehydes as Key Intermediates

Alexandros Mavroskoufis; Samuel Deckert; Carolin Fopp; Hakon Hertwig; Jakob John Schydlo; Mrinal K. Bera; Reinhold Zimmer; Hans-Ulrich Reissig

doi:10.1055/s-0043-1763757

Synthesis, Inhaltsverzeichnis

Synthesis 2025; 57(01): 125-137
DOI: 10.1055/s-0043-1763757

paper

Special Topic Dedicated to Prof. H. Ila

Synthesis of Heterocyclic Compounds with Pyrimidine-4-carbaldehydes as Key Intermediates

Authors

Alexandros Mavroskoufis

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Samuel Deckert

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Carolin Fopp

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Hakon Hertwig

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Jakob John Schydlo

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Mrinal K. Bera

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

^bDepartment of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, PO-Botanic Garden, Howrah-711 103 (WB), India
Reinhold Zimmer∗

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
Hans-Ulrich Reissig ∗

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

Abstract

Alle Artikel dieser Rubrik

Dedicated to Professor Hiriyakkanavar Ila in great admiration of her creative contributions to heterocyclic chemistry

Abstract

With the motivation to expand the compound library of specifically substituted pyrimidine derivatives, we prepared several pyrimidine-4-carbaldehydes. In most cases, the chemoselective oxidation of 4-hydroxymethyl-substituted pyrimidine derivatives could be achieved in good yields to provide the desired compounds. Alternatively, the aldehydes were prepared by Riley oxidation with selenium dioxide from the corresponding 4-methylpyrimidines. The formyl group of these compounds was employed as handle to generate alkynyl, cyano, oxazol-5-yl or β-ketoester substituents. Furthermore, two methods were found to prepare furo[3,2-d]pyrimidines. A serendipitously discovered reaction to a 6-(pyrimidin-4-yl)furo[3,2-d]pyrimidin-7-ol derivative involves a mechanistically interestingly ‘dimerization’ process with a benzoin addition as key step. Other compounds in this series contain amino, azido, or 1,2,3-triazol-1-yl groups. All these transformations to highly substituted pyrimidine derivatives demonstrate the synthetic versatility of pyrimidine-4-carbaldehydes and similar compounds.

Key words

azides - furo[3,2-d]pyrimidines - nitriles - oxazoles - oxidation - pyrimidine-4-carbaldehyde - triazoles

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