Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Acid Catalyzed Amination of 4-Chloropyrrolopyrimidine: Effect of Solvent, Acid Amount and Substrate Scope for Reactions in Water

Version 1 : Received: 12 October 2023 / Approved: 12 October 2023 / Online: 12 October 2023 (14:36:25 CEST)

How to cite: Svergja, H.; Yasuda, S.; Olsen, C. E.; Hoff, B. H. Acid Catalyzed Amination of 4-Chloropyrrolopyrimidine: Effect of Solvent, Acid Amount and Substrate Scope for Reactions in Water. Preprints 2023, 2023100837. https://doi.org/10.20944/preprints202310.0837.v1 Svergja, H.; Yasuda, S.; Olsen, C. E.; Hoff, B. H. Acid Catalyzed Amination of 4-Chloropyrrolopyrimidine: Effect of Solvent, Acid Amount and Substrate Scope for Reactions in Water. Preprints 2023, 2023100837. https://doi.org/10.20944/preprints202310.0837.v1

Abstract

Acid promoted amination of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine with anilines have been studied using hydrochloric acid. Four alcoholic solvents and water were evaluated as reaction medium, and the highest rate was observed in water. Although the initial rate increased by using higher concentration of acid, this leads to more solvolysis of the pyrrolopyrimidine, reducing the potential yield. The substrate scope of the amination of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine in water using 0.1 equivalent of hydrochloric acid was evaluated using 20 aniline derivatives with variance in basicity and steric bulk. Preparative useful reactions were seen for 14 of the 20 derivatives. Unsuited anilines are ortho substituted anilines with a pKa below 1. Aliphatic and benzylic amines react poorly under these conditions, but such aminations can proceed well in water without acid. Pyrrolopyrimidines with a low water solubility, also reacted slowly in water, however they could easily be aminated in 2-propanol.

Keywords

acid catalysed amination; anilines; pyrrolopyrimidine; nucleophilic aromatic substitution, pKa .

Subject

Chemistry and Materials Science, Organic Chemistry

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