5-Fluorosalicylaldehyde

Chemical Properties

White solid

Uses

5-Fluorosalicylaldehyde may be used to synthesize:

• managanese (III) complex [MnL^a(μ_1,3-N₃)]_n [H₂L^a = N,N′-bis(5-fluorosalicylidene)-1,2-diaminoethane]
• enantiopure 4-amino-6-fluoro-3-(hydroxymethyl)chromanes
• 4,4′-difluoro-2,2′-[(hydrazine-1,2-diylidene)bis(methanylylidene)]-diphenol
• N,N′-bis(5-fluoro-2-hydroxybenzylidene)ethylenediamine
• N,N′-(2-hydroxypropane-1,3-diyl)-bis(salicylaldimine (H₂L)

General Description

5-Fluorosalicylaldehyde can be synthesized from 4-fluorophenol.

Synthesis

The general procedure for the synthesis of 5-fluorosalicylaldehyde from 4-fluorophenol and trichloromethane is as follows: Step A: To a solution of water (400mL) containing NaOH (78g, 1950mmol) was added a mixture of 4-fluorophenol (50g, 446.43mmol) in water (200mL) and ethanol (150mL). After heating the mixture to 70°C, trichloromethane (110 mL) was slowly added dropwise through the addition funnel (approximately 2 hours to complete the drop) and the reaction mixture was continuously stirred at this temperature overnight (approximately 16 hours). Upon completion of the reaction, the mixture was cooled to room temperature and acidified with 3M HCl solution. Subsequently, the reaction mixture was partitioned between saturated saline and dichloromethane, the organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography (eluent: 3% ethyl acetate/hexane) to afford 13.6 g of 5-fluorosalicylaldehyde (22% yield, white solid).

References

[1] Journal of the American Chemical Society, 1998, vol. 120, # 33, p. 8340 - 8347
[2] Patent: WO2005/37763, 2005, A1. Location in patent: Page/Page column 126
[3] Patent: US2017/37038, 2017, A1. Location in patent: Paragraph 0372; 0373; 0374
[4] Journal of the American Chemical Society, 1946, vol. 68, p. 2502
[5] European Journal of Medicinal Chemistry, 1996, vol. 31, # 6, p. 449 - 460