Benzothiazole-2-sulfonyl chloride

Interpretation of the stereo- and chemoselectivity of oxidation reactions using thianthrene oxide must consider its low barrier to ring-inversion, steric effects, and the role that solvents may play in the product distribution. All of these possibilities could influence the Xso value of oxidants. Specifically, mechanistic consideration of electrophilic oxidation of thianthrene oxide in the presence of protic solvents or acid leads to diminished yields of SSO2. Despite aU of these concerns, benzothianthrene oxide is still considered a reliable probe for the electronic character of oxidants. 

Mark W. Peczuh Chrysa F. Malosh University of Connecticut, Storrs, CT, USA 

Solubility soluble in most common organic solvents. 

Handling, Storage, and Precaution this material should not be stored at room temperature for any length of time. The author has had room temperature sanples spontaneously decompose with liberation of SO2. The rate at which this occurs is quality dependent. Dilute solutions in CHCI3 (0.1 M) are relatively stable but a 1 M solution decoirposes within 3 days. The stability in solution is iirproved by the addition of 1% BHT. 

Reagent Preparation. The reagent is easily prepared by a chlorine oxidation of commercially available 2-mercaptobenzo-thiazole.  

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CI2 gas was bubbled at 0°C into 33% AcOH in HjO (60 mL). After a yellow precipitate formed, a suspension of l,3-benzothiazole-2-thiol (10.0 g, 60 mmol) in 33% AcOH in HjO (60 mL) was added in ca. 20 portions over 2 h still with Cb bubbling through the mixture (internal temperature was maintained at 0 °C). A large excess of Clj is essential. The yellow suspension was stirred at 0 °C for further 15 min. The mixture was filtered through a cooled filter, the solid was washed with ice water (100 mL) and dissolved in CH2CI2 (100 mL), and the clear soln was washed with NaHC03 (100 mL), and cold brine. The organic phase was dried (powdered molecular sieves 4 A) at 0 °C over 1 h, and filtered. The soln was concentrated and dissolved in EtjO (20 mL), cooled to —78°C, filtered and washed with EtjO (10 mL) yield 9.6-10.0 g (69-72%) white needles mp 105-108 °C (dec). Freshly prepared l,3-benzothiazole-2-sulfonyl chloride is stable at rt for several hours, a smell of SO2 indicates decomposition after several days. 

The first examples were benzene disulfonimide derivatives prepared from o-benzenebis(sulfonyl chloride) or -disulfinic acid with amines or HNO2 respectively <84CHEC-I(6)914>, or benzothiazole derivatives (94) obtained from benzenesulfonamides or azides containing ortho SR or SOR groups... 

Methyl-l,3,4-thiadiazole-2-sulfonyl chloride was prepared as described for l,3-benzothiazole-2-sulfo-nyl chloride except that 5-methyl-l,3,4-thiadiazole-2-thiol was added as a solid over 30 min instead of as a suspension in aq AcOH over 2h. Moreover, EtjO was used instead of CH2CI2 for extraction, and Na2S04 instead of molecular sieves yield 80% mp 44-48 °C (EtjO). 

Treatment of benzothiazole with an excess of chlorosulfonic acid and then thionyl chloride affords a 4 1 mixture of the 4- and 7-sulfonyl chlorides, respectively. Chlorosulfonic acid alone fails to react with benzothiazole. This is probably due to the formation of the 4-sulfonic acid where an intramolecular hydrogen bond inhibits the formation of the chlorinated derivative <92PS(73)107>. Interestingly, when the same reaction is carried out with 2-methylbenzothiazole the major product is the 6-sulfonyl chloride. 

The sulfonamide 184 is an intermediate in the synthesis of herbicidal N-(pyrimidine aminocarbonyl) thiazolesulfonamides. In addition, several sulfonyl derivatives of isoxazole, pyrazole and thiazole have shown antifungal activity. Benzothiazole 185 is reported to react with chlorosulfonic acid to only give a salt later repetition" of the reaetion with chlorosulfonic acid at both RT and 100 °C confirmed this result. On the other hand, when benzothiazole 185 was heated with excess chlorosulfonic acid (six equivalents) at 150 °C (4i hours), followed by boiling with thionyl chloride (2 hours), the reaction gave the sulfonyl chloride as a gum. Subsequent treatment with amines afforded a mixture of the 4-and 7-sulfonamides 186 and 187 respectively (Equation 49)." ... 

The NMR spectra of the dimethylamide derivatives 186 R = Me and 187 R = Me, indicated that the product mixture contained 80% of the 4-sulfonamide and 20% of 7-isomer." The failure of the action of chlorosulfonic acid alone on benzothiazole to yield the sulfonyl chloride may be due to the 4-sulfonic acid existing as the stabilized hydrogen-bonded structure 188 which requires a more powerful chlorinating agent (thionyl chloride) to convert it into the sulfonyl chloride. This is analogous to the situation previously observed in the chlorosulfo-nation of diarylureas (see Chapter 4, p 112)... 

Dimethoxyphenyl)benzothiazole 192 reacts with excess chlorosulfonic acid to give the 5-sulfonyl chloride 193 in this reaction sulfonation has occurred in the least hindered /lara-position with respect to the electron-donating methoxy group (Equation... 

Use as a Protecting Group for Nitrogen. Vedejs, who showed that benzothiazole-2-sulfonyl-aminoacids (Bts-aminoacids) could readily be converted to their acid chlorides without racemization, pioneered the use of the Bts group for the protection of amino acids. The acid chloride of Bts-protected amino acids were found to be effective for racemization free peptide couplings. The sulfonamide is readily prepared using... 

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