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. Preprints2023, 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
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. Preprints2023, 2023100837. https://doi.org/10.20944/preprints202310.0837.v1
APA Style
Svergja, H., Yasuda, S., Olsen, C. E., & Hoff, B. H. (2023). Acid Catalyzed Amination of 4-Chloropyrrolopyrimidine: Effect of Solvent, Acid Amount and Substrate Scope for Reactions in Water. Preprints. https://doi.org/10.20944/preprints202310.0837.v1
Chicago/Turabian Style
Svergja, H., Cecilie Elisabeth Olsen and Bård Helge Hoff. 2023 "Acid Catalyzed Amination of 4-Chloropyrrolopyrimidine: Effect of Solvent, Acid Amount and Substrate Scope for Reactions in Water" Preprints. 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.
Chemistry and Materials Science, Organic Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
