3-Ethyl-2-fluorobenzothiazolium Tetrafluoroborate1

[60150-69-3]  · C9H9BF5NS  · 3-Ethyl-2-fluorobenzothiazolium Tetrafluoroborate  · (MW 269.04)

(transformation of alcohols to alkyl halides;2 optical inversion of secondary alcohols;3 esterification of carboxylic acids;4 cyclization of alcohols5)

Solubility: insol CH2Cl2; reacts with alcohols.

Preparative Methods: treatment of 2-fluorobenzothiazole with Meerwein's reagent (Triethyloxonium Tetrafluoroborate).1

Handling, Storage, and Precautions: hygroscopic salt; handle cautiously, the toxicity of this reagent has not been reported.

Alkyl Halides.

2-Halobenzothiazolium salts react readily with alcohols to form an alkoxybenzothiazolium salt. This intermediate reacts with alkali metal halides to form alkyl halides in good yield (eq 1).2

The general procedure is to suspend the benzothiazolium salt in CH2Cl2 and add the alcohol and Triethylamine dropwise. This is followed by addition of the alkali halide in acetone or DMF. Inverted alkyl halides are obtained with optically active secondary alcohols (eq 2).2

There are a variety of ways to convert alcohols to halides. The most common is halogen acids HX or inorganic acid halides such as Thionyl Chloride.6 However, treatment of secondary alcohols with these reagents often gives rearranged products instead of the inverted alkyl halide.

A benzoxazolium salt (1) gives comparable yields with acyclic alcohols, and it gives good yields of the inverted halide with cyclic alcohols (eq 3).7 The benzothiazolium salt does not give satisfactory results for these types of alcohols (see also 2-Chloro-3-ethylbenzoxazolium Tetrafluoroborate).

Inversion of Secondary Alcohols.

Reaction of alkoxybenzothiazolium salts with Trichloroacetic Acid gives esters with an inverted stereocenter. These are saponified under mild conditions to give the inverted secondary alcohol in good yield (eq 4).3

Another method often used for inverting secondary alcohols is the Mitsunobu reaction involving treatment of the alcohol with Triphenylphosphine and Diethyl Azodicarboxylate.8

Ester Formation.

2-Halobenzothiazolium salts have been used to synthesize esters from carboxylic acids and alcohols (eq 5).4 This is similar to (eq 4) except a more stable ester is formed when the trichloro substitution is avoided.

There are many useful reagents for synthesizing esters from carboxylic acids. Many of them are commercially available and are more practical than the benzothiazolium salts (see N,N-Carbonyldiimidazole, 1-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide, 1,3-Dicyclohexylcarbodiimide, 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Hydrochloride, and 1,1-Thionylimidazole).

Cyclization of Alcohols.

A similar 2-fluorobenzothiazolium salt (2) has been used in the dehydrative cyclization of sesquiterpene alcohols (eq 6).5

Presumably this would work similarly with the N-ethylbenzothiazolium salt. Yields of the desired products are lower when the reaction temperature is -78 °C. Compound (2) is the most effective reagent for this transformation. The benzoxazolium salt (1) gives about 45% of the desired products under similar conditions. The 2-fluoropyridinium salt (3) gives 58% of the desired products at -40 °C (see also 2-Chloro-3-ethylbenzoxazolium Tetrafluoroborate).

1. Fieser, M. FF 1980, 8, 223.
2. Hojo, K.; Mukaiyama, T. CL 1976, 619.
3. Mukaiyama, T.; Hojo, K. CL 1976, 893.
4. Mukaiyama, T.; Hojo, K. CL 1976, 267.
5. Kobayashi, S.; Tsutsui, M.; Mukaiyama, T. CL 1977, 1169.
6. Pizey, J. S. Synthetic Reagents; Wiley: New York, 1974; Vol 1, pp 321-357.
7. Mukaiyama, T. Shoda, S.; Watanabe, Y. CL 1977, 383.
8. Bose, A. K.; Lal, B.; Hoffman, III, W. A.; Manhas, M. S. TL 1973, 1619.

Richard S. Pottorf

Marion Merrell Dow Research Institute, Cincinnati, OH, USA

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