2.1- Benzisoxazole, 3- rearrangement

Among ring-fused systems, the 3-(o-aminoaryl)benzisoxazole (506) underwent rearrangement on refluxing in THF with sodium hydride or lithium aluminum hydride. In this case the 3-(o-hydroxyphenyl)benzimidazole (506a) was obtained. 

Photochemical studies on the ring degradation of 3-hydroxy-l,2-benzisoxazole also yielded benzoxazolone, and (40), (41) and (42) (Scheme 14) were believed to be potential intermediates. Low temperature IR measurements indicated the presence of (42) during the photochemical reaction (73JA919, 71DIS(B)4483, 71JOC1088). Sensitization studies indicate that the rearrangement is predominantly a triplet reaction, and the keto tautomer is believed to be the key orientation for the photolysis. 

Acylation of 3-alkyl-6-hydroxy-l,2-benzisoxazole has also been reported (77JIC875) under Friedel-Crafts conditions to give the 7-acyl product. Fries rearrangement of 6-acetoxy-3-methyl-1,2-benzisoxazole in the presence of AICI3 at 140 °C also provides a route to the 7-acetyl-6-hydroxy derivatives (73UC541). Reactions of these kind are rare in this series. 

Related 1,2-benzisoxazole derivatives such as 3-(o-aminoaryl)benzisoxazoles (276) undergo rearrangement on refluxing in THF solution in the presence of NaH or LiAlH4, giving the indazoles (277) (74JHC885). 

Several 3-acylamino-l,2-benzisoxazoles such as (278) underwent rearrangement to 3-(o-hydroxyphenyl)-l,2,4-oxadiazoles (279) on heating with base. It has been questioned whether the same mechanism is operative in these last rearrangements (8lAHC(29)l4l, p. 150). 

The course of the reaction is dependent on the configuration of the oxime. The (Z)-oxime gave 1,2-benzisoxazoles as the primary product while the (E)-oxime generally produced a Beckmann rearrangement product with or without subsequent cyclization to a benzisoxazole (Scheme 167) (67AHC(8)277). Bunnett conducted a kinetic study on the reaction shown in Scheme 167 and determined that cyclization to intermediate (551) was the rate determining step (61JA3805). 

The Af-oxide of indolone rearranged to produce 3-benzoyl-2,1-benzisoxazole (65JOC1104, and an isoxazolyl-2,1-benzisoxazole (587) was prepared from a benzilideneacetylacetone... 

The l,3-dihydro-2,l-benzisoxazole-3-carboxyIic acid was prepared by either base treatment of N-hydroxyisatin or the rearrangement of N-hydroxyisatin monooxime with dilute acid (67AHC(8)277). The addition of amines to 3-unsubstituted-2,l-benzisoxazolium salts gave 3-amino-l,3-dihydro-2,l-benzisoxazoles (72CPB2209). 

Acylation of mesoionic pyrido[l,2-u]pyrimidin-4-ones 150 with aroyl chlorides in the presence of NEts yielded 2-aroyloxy-4//-pyrido[l,2-u]pyrimidin-4-ones 178 (96JHC663). None of the esters 178 could be rearranged to the 2-hydroxy-3-aroyl derivatives 179. The hydroxy group of 9-hydroxy-2-methyl-3- 2-[4-(6-fluoro-l,2-benzisoxazol-3-yl)-l-piperidinyl] ethyl -6,7,8,9-tetrahydro-4//-pyrido[l, 2-u]pyrimidin-4-one was acylated with hexadecanoic acid in CH2CI2 in the presence of dicyclohexylcarbodi-imide and 4-pyrrolidinopyridine at room temperature for 3 days in 80% yield (97MIP7). 

The principal methods for forming the heterocyclic ring of benzofuroxans involve oxidation of o-quinone dioximes, thermolysis of o-nitroaryl azides, and oxidation of o-nitroanilines (Scheme 25). Ring chain tautomerism (Section 4.05.5.2.1) for the A -oxides of asymmetrically substituted benzofuroxans is more facile than for monocyclic analogues and mixtures of isomers may result. Benzofuroxans are also formed by Boulton-Katritzky rearrangement of 7-nitro-2,l-benzisoxazoles and 4(7)-nitrobenzofuroxans (Section 4.05.5.2.5). 

Pyrolysis of the 2-(2-azidobenzoyl)pyridines 334 (R and R = H or Br) at llO C gives the benzisoxazoles 335, which rearrange to the mesomeric betaines 338 in good yield at higher temperatures (215°C). The yellow, crystalline betaines (v q 1640 cm ) are stable compounds whose structure is supported by an X-ray crystallographic study of the bromo derivative 338 (R = H, = Br). The following reactions of the parent system (338 R = R2 = H) have been reported (Scheme 13) (i) Nitration gives the 2-nitro... 

Cyclic sulfite 23 formed benzisoxazole 24 with 94% yield in the presence of diisopropylethylamine <2005JOC8560>. Although the mechanism of the cyclic sulfite 23 rearrangement has not been fully delineated, simple kinetic experiments showed that the rate of formation of benzisoxazole 24 was second order in the concentration of 23 and first order in the concentration of diisopropylethylamine (Equation 1). 

The isoxazole-to-oxazole rearrangement has been also used in the synthesis of benzocondensed derivatives. The irradiation of benzisoxazoles 81 in water (high-pressure Hg lamp) produces almost quantitative yields of the corresponding ben-zoxazoles 82 (Scheme 12.24) [53]. Benzoxazolin-2-ones 83 are similarly obtained [54], Furthermore, oxazolo[5,4-b]pyridines 84 and oxazolo[5,4-b]quinoline 85 are obtained by preparative-scale photolysis in ether with a high-pressure Hg lamp of the corresponding isoxazolo[5,4-b]pyridines or isoxazolo[5,4-b]quinoline, respectively (Scheme 12.24) [55]. 

The hydroxide ion induced rearrangement of Af-hydroxyisatin to 2,l-benzisoxazole-3-carboxylic acid has been described. A 14C label at the 3-position produced a 2,1-benzisoxazole with the label in the carboxyl carbon (Scheme 184) <66DIS(B)102). 

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