Fluorinated Amines

Fluorinated Aliphatic Amines and Amidines

Fluorinated Aromatic Amines and Anilines

Introduction

Fluorinated amines are one of the functional building blocks with high market demand in recent years. On the one hand, the introduction of fluorine element weakens the basicity of amines and enhances the metabolic stability. On the other hand, basic nitrogen-containing groups play an important role in regulating the properties of bioactive molecules. Therefore, no matter in laboratory research or in the field of production application, fluorinated amines have great synthetic research value. People are also paying close attention to finding effective ways to construct the structure of fluoroamines.

Synthesis

Fluorinated amines are important organic intermediates, which are mainly synthesized by hydrogenation reduction or fluoroamination.

• Hydrogenation reduction. Reduction reactions are an important class of reactions widely used in the synthesis of amines in the laboratory and industry. Among them, reduction reactions using hydrogen are crucial for the economical and sustainable production of different types of amines, especially fluorinated amines. Hydrogenation reduction can prepare fluorinated amines by reducing readily available fluorine-containing nitro compounds in the presence of suitable catalysts and hydrogen. For example, p-trifluoromethylaniline can be prepared by hydrogenation reduction of p-trifluoromethylnitrobenzene using Pd/C as a catalyst.

Fig.1 Synthesis of fluorinated amines through hydrogenation reduction

• Fluoroamination. Fluoroamination of alkenes is an ideal strategy for the synthesis of fluorinated amines, which can introduce fluorine-containing groups and nitrogen-containing groups into organic molecules in one step. For example, Fu's group reported the three-component electron-rich fluoroamination reaction of olefins, and synthesized a series of fluorinated amines. They used one equivalent of olefins, two equivalents of dialkylnitrogen bromides, three equivalents of AgF, 20 mol% tridentate ligand (L) and one equivalent of 4-dimethylaminopyridine (DMAP) as additives in a mixed solvent of HFIP/DCM at 40 ℃. After three hours, the fluoroaminated target product can be obtained in the best yield^[1].

Fig.2 Synthesis of fluorinated amines through fluoroamination

Applications

Fluorinated amines building blocks have good applications in the fields of medicine and pesticides, and the future market prospects are promising.

• Medicine. As important fluorinated building blocks, fluorinated amines have great potential in the development of new drugs. The curative effect of fluorinated amine drugs is stronger than that of ordinary drugs due to the modification effect of fluorine element. At present, a large number of fluorinated amines have been used in the synthesis of drugs. For example, 3-chloro-4-fluoroaniline can be used in the synthesis of the fluoroquinolone antibacterial drug norfloxacin. m-Trifluoromethylaniline can be used to synthesize the non-steroidal anti-inflammatory analgesic drug flufenamic acid and the new non-steroidal drug for the treatment of dermatological diseases, ufenamate.
• Pesticides. Fluorinated amines building blocks are also widely used in the synthesis of herbicides, pesticides, etc. They are environmentally friendly and safe for organisms. For example, 2,6-difluoroaniline can be used to synthesize the benzoyl urea herbicide flumetsulam. m-Trifluoromethylaniline can be used to synthesize the upland herbicide fluometuron.

Alfa Chemistry can offer various fluorinated amines building blocks. You can click on our product list for a detailed view. At the same time, we also offer product customization according to customer's detailed requirements. If you are interested in our products, please feel free to contact us. We will be happy to provide you with support and services.

Reference

1. Yang, L.; et al. Three-component aminofluorination of alkenes with electronically rich amino sources. Chem. 2022, 8(4): 1147-1163.