1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate): Its application and toxicity

General description

1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2] octane bis (tetrafluoroborate), also named as Selectfluor, is a kind of selective fluorine reagent. Due to the presence of trifluoromethyl in the molecule, the lipophilicity of the molecule is increased, and the transport of fluorinated molecules in the physiological system is improved. The function of fluoride is considered to inhibit, alternate and strengthen the normal physiological process. Most fluorinating agents generally have high toxicity and high activity. A lot of work in the field of organic fluorine chemistry often needs to be carried out in laboratories with special conditions. This reagent is not only one of the most reactive electrophilic fluorinating reagents available, but it is also safe, nontoxic, and easy to handle. Its appearance is as follows:

Figure 1 Appearance of 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2] octane bis (tetrafluoroborate).

Characteristics

Fluorine in the 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2] octane bis (tetrafluoroborate) is the most electronegative element. The carbon-fluorine single bond is stronger than the single bond formed by the combination of carbon and other element atoms. Therefore, the bond length is shorter and the C-F bond is difficult to break. At the same time, 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) has the smallest radius of fluorine atoms, which can just wrap the carbon chain skeleton tightly, playing a good shielding and protection role, making it not vulnerable to chemical reactions due to the attack of other atoms. In an extreme experiment to demonstrate its stability (and to satisfy the United States Department of Transportation regarding the risks associated with transporting a potentially dangerous compound), a self-accelerating decomposition temperature (SADT) test was performed, in which a 55-gallon drum filled with selectfluor was heated to 568C for 7 days; during this time the temperature remained constant within Æ 58C [1].

1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) has been found to be stable at temperatures up to 1958C, although the inventors warn that bulk samples should only be heated above 808C with caution [2]. Therefore, a significant advantage of the selectfluor reagent remains its remarkable stability, as a result of which it has become a commercially available, hazard-free source of fluorine.

Application

1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) is a versatile reagent for fluoroalkylation of alkenes and acetylenes under mild conditions. It is safe, stable, highly reactive, and amenable to industrial production. This reaction follows Markovnikov-type regioselectivity [3]. It also helps in the deprotection of PMP, THP, and 1,3-dithiones. Acetonitrile and nitromethane (5% H2O content) can be used as solvent. In the presence of 1.2 equivalents of Select- fluor, deprotection is complete in five hours [4].

1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) acts as a mediator for the introduction of a per- fluoroalkyl moiety containing a functional group at the benzylic position in hexamethylbenzene, in the presence of polyfluoroalco- hol or potassium salts of perfluoroalkane carboxylic acid [5]. 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) provides one-pot fluorination and anomeric func- tionalisation of a carbohydrate. In the presence of a nucleophile, it reacts with glycals to give 2-deoxy-2-fluoro derivatives with concurrent introduction of a nucleophile to the anomeric position [6]. It can be used as an excellent promoter for allylation of aldehydes and amines with allyltributyltin in one step, to form homoallylic alcohols or amines [7].

Toxicity

1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) is relatively harmless. Toxicology studies revealed an oral LD50 (dose needed to kill 50% of the subjects) of 640 mgkg À1 for male adult rats; skin exposure up to 2.0 gkg À1 led to no lethality in rats. [8] Only mild eye and skin irritation was observed in studies with rabbits and guinea pigs. It also failed to demonstrate any signs of mutagenic or carcinogenic activity. Studies showed that the ecological and environmental effects of selectfluor were also minor: Its impact on algal growth, sewage-sludge respiration, and the toxicity of several species were found to be within acceptable levels.

References

[1]J. J. Hart, R. G. Syvret, J. Fluorine Chem. 1999, 100, 157.

[2]R. E. Banks, M. K. Besheesh, S. N. Mohialdin-Khaffaf, I. Sharif, J. Chem. Soc. Perkin Trans. 1 1996, 2069.

[3]Stavber, S.; Sotler, T.; Zupan, M. Tetahedron Lett. 1994, 35, 1105.

[4]Liu, J.; Wong, C.-H. Tetrahedron Lett. 2002, 43, 4037.

[5]Stavber, S.; Kralj, P.; Zupan, M. Acta Chim. Solv. 2002, 49, 5537; Chem. Abstr . 2003, 138, 169926k.

[6]Burkart, M. D.; Zhang, Z.; Hung, S.-C.; Wong, C.-H. J. Am. Chem. Soc. 1997, 119, 11743.

[7]Liu, J.; Wong, C.-H. Tetrahedron Lett. 2002, 43, 3915.

[8]Nyffeler, P. T.; Duro?n, S. G.; Burkart, M. D.; Vincent, S. P.; Wong, C.-H. Angew. Chem. Int. Ed. 2005, 44, 192.

You may like