2,1-Benzisothiazoles from 2,1-benzisoxazoles

Phosphorus pentasulfide is used to replace oxygen atoms with sulfur atoms the reaction is commonly carried out in a solvent heated under reflux. Solvents employed include carbon disulfide, aromatic hydrocarbons, and pyridine. If an oxygen atom is part of a heterocycle, then the reagent may replace it with sulfur, as in the formation of 2,1-benzisothiazoles from 2,1-benzisoxazoles.119 Such replacements are, however, not general some prior ring opening appears to be necessary before the reagent can act. For example, under normal conditions furan is not attacked. 

Imidazole phosphorus pentasulfide 2,1-Benzisothiazoles from 2,1-benzisoxazoles... 

Benzisothiazoles are best prepared by oxidative cyclization of o-aminothiobenz-amides (see Section 4.17.9.1.1), reaction of o-toluidines with thionyl chloride (see Section 4.17.9.2.1) or by sulfuration of 2,1-benzisoxazoles (see Section 4.17.10.2). 1,2-Benzisothiazoles can also be prepared from o-disubstituted benzene compounds, cyclodehydration of o-mercaptobenzaldoximes or oxidative cyclization of p-mercaptobenzylamines (see Section 4.17.9.1.1) being the most convenient. Both series of benzo compounds are readily substituted at the 5- and 7-positions by electrophilic reagents. 

A unique example is found in 2,1-benzisoxazole (40), which undergoes N-methylation 1.9 times faster than isoxazole (37).122 This is the only known example of rate acceleration resulting from benzo-fusion. Other interesting comparisons involve 2,1,3-benzoxadiazole (benzofurazan, 41), and 1,2,5-oxadiazole (furazan, 42),123 and also isothiazole (37), and 2,1-benzisothiazole (40).122 For these two pairs essentially no change in reactivity results when the azole is converted into its benzolog. 

All these special cases involve benzologs with an ortho quinonoid structure. But even this pattern is not universal, a deviation being 2-methylindazole (40), which quaternizes 2.2 times more slowly than its parent compound 1-methylpyrazole (37).122 Indeed, except for the molecules just considered and 1,2-benzisothiazole,122 benzo-fusion is rate retarding. Thus, 1,2-benzisoxazole (indoxazene, 39), reacts 3.2 times, and 1-methylindazole (39) 7.1 times, more slowly than their parent compounds.122 Fusing a benzene ring onto an azole where the heteroatoms are situated 1,3 leads to decreases in rate constants by factors of 5.0, 6.3, and 6.8, respectively, when X of 38 is NMe, S, and O.122 These factors are not much smaller than that obtained from a comparison of pyridine and quinoline reactivities.61,78,79... 

Few details of the infrared spectra of 2,1-benzisothiazoles have been reported. Some infrared and NMR spectra are available from commercial reference collections.112 The molecular refraction of 2,1-benzisothiazoles is similar to that of 2,1-benzisoxazole.113... 

Similarly to 1,2-benzisoxazoles, 1,2-benzisothiazoles with the nitro group in the arylene fragment can be obtained from 4-mercaptotocumarines and from hydroxy-lamine [167],... 

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