2-(Pyrimidin-5-yl)benzaldehyde

Uses

2-(Pyrimidin-5-yl)benzaldehyde is a temporary directing group (TDG) to assist as a co-catalyst for metal catalyzed C-H functionalization. Often in C-H functionalization, an auxiliary compound is used to control site selectivity. These traditionally are covalently bonded to the compound of interest, and must subsequently be removed after functionalization, like a typical protecting group. To simplify the process of C-H functionalization, 2-fluoro-6-(pyrimidin-5-yl)aniline is one of a series of temporary directing groups developed by Deb Maitiμs lab th at promote site selectivity without the inclusion of additional synthetic steps.

2-(pyrimidin-5-yl)benzaldehyde is an effective TDG for meta directed C-H functionalization of amine substituted target compounds, with high selectivity.

Synthesis

GENERAL STEPS: 2-formylphenylboronic acid (290 mg, 2.0 mmol), 5-bromopyrimidine (316 mg, 2.0 mmol), and acetonitrile (8 mL) were added sequentially to a 20 mL microwave reaction tube. Subsequently, 1 M aqueous sodium carbonate (4 mL) and dichlorobis(triphenylphosphine)palladium(II) (100 mg) were added to the mixture. The reaction tube was sealed and the reaction was carried out by microwave radiation at 150 °C for 5 min. After completion of the reaction, the reaction was cooled to room temperature and the reaction mixture was extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure to obtain the crude product. The crude product was purified by ISCO fast chromatography system to obtain the target compound 2-(pyrimidin-5-yl)benzaldehyde (220 mg).

References

[1] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 18, p. 8607 - 8618
[2] Patent: US2008/153852, 2008, A1. Location in patent: Page/Page column 27
[3] Patent: CN104045626, 2017, B. Location in patent: Paragraph 0318