2,1-Benzisoxazole 4-nitro

Nitration of 3-ethyI-l,2-benzisoxazoIe 2-oxide (57) and reduction under forcing conditions with triethyl phosphite gave 6-nitro-l,2-benzisoxazoIe. In contrast, nitration of 2-ethyI-1,2-benzisoxazole gave 5-nitro substitution (Scheme 23) (80CC421). 

Nitration of a series of methyl-1,2-benzisoxazoles was studied by Tahkar and Bhawal using fuming nitric acid and sulfuric acid in acetic acid at 100 °C. 3-Methyl-1,2-benzisoxazole gave a mixture of 5-nitro- and 5,7-dinitro-3-methyl-l,2-benzisoxazole, with the 5-nitro isomer predominant. The product obtained from 3,5-dimethyl-1,2-benzisoxazole was the 4-nitro derivative and not the 7-nitro compound as proposed by Lindemann (26LA(449)63). The synthesis of the 7-nitro compound by an alternative method was used as structural proof. Two products were obtained from 3,6-dimethyl-l,2-benzisoxazole and these were the 5-nitro and 5,7-dinitro derivatives. 3,7-Dimethyl-l,2-benzisoxazole was converted into the 5-nitro derivative (Scheme 25) (77lJC(B)l06l). 

Nitration of 3-chloro-1,2-benzisoxazole gave the 5-nitro derivative (80ZC18, 79ZC452), as did nitration of l,2-benzisoxazole-3-acetic acid with fuming nitric acid. Under more forcing... 

Benzisoxazole or 3-methyl-2,l-benzisoxazole when treated with KNO3 in sulfuric acid produced the 5-nitro compound as the main product, with some of the 7-nitro as a side product (6.3MI41601, 65CC408). 

Reduction of 3,5-dimethyl-7-nitro-l,2-benzisoxazole with SnCU and HCl produced both the 7-amino compound and a 4-chloro-7-amino derivative (Scheme 28) (67AHC(8)277). 

Nitration of 3-phenyl-1,2-benzisoxazole with fuming nitric acid has been shown to give dinitro products of undetermined substitution pattern (67AHC(8)277, p. 290>. However, more satisfactory studies have now been described, especially on the kinetics and mechanism of nitration of 3-methyl-l,2-benzisoxazole (77JCS(P2)47). Nitration in cold, concentrated mixed acids yields the 5-nitro derivative exclusively, nitration in 80-90% sulfuric acid occurring on the free base whereas at higher acidities the conjugate acid is the species involved in the nitration. 

However, other studies on the nitration of a series of 3-methyl- and 3-ethyl-1,2-benzisoxazoles have shown that a mixture of the 5-nitro and 5,7-dinitro derivatives is formed (77IJC(B)1058, 77IJC(B)1061). The effect of substituents in the benzene ring is also of interest. If the 5-position is blocked, e.g. by a chloro group or by alkyl groups, nitration then occurs at the 4-position. 3-Alkyl-7-chloro and 3,7-dialkyl derivatives result in the formation of the appropriate 5-nitro derivative. The isomeric 3-alkyl-6-chloro- and 3,6-dialkyl-1,2-benzisoxazoles yield a mixture of the 5-nitro and 5,7-dinitro compounds. Both H NMR measurements and alternate syntheses were used in establishing the structures of these substitution products. 

Nitro groups in the homocyclic ring of 1,2-benzisoxazoles have been reduced to the corresponding amino groups without opening of the isoxazole nucleus. SnCU/HCl and Adam s catalyst/H2 have both proved effective in this respect. Similar behavior was observed for nitro groups in the isomeric 2,1-benzisoxazoles (67AHC(8)277,pp.295,33l). 

The intermediacy of an aci-nitro compound has been proposed for the sulfuric acid cyclization of o-nitrophenylacetic acid to yield a mixture of 2,1-benzisoxazole and 2,1-benzisoxazole-3-carboxylic acid. The acid does not decarboxylate under the reaction conditions. The proposed aci-nitro intermediate cyclized to an A/ -hydroxy compound which decomposed to the products (Scheme 179) (70JCS(C)2660). 

As with the isomers, 5-halogenation of 2,1-benzisoxazoles is favored, but this may be a consequence of an initially formed 4,5-addition product. Such an adduct has been isolated during chlorination [66T(S7)49 67AHC(8)277]. When 6-nitro-2,l-benzisoxazole-3-carboxylic acid (38)... 

One of the earliest reports on the use of dendrimers in catalysis is the unimolecu-lar decarboxylation of 6-nitro-benzisoxazole-3-carboxylate in the presence of a dendrimer comprising ether dendrons which are functionalized at their periphery with tetra-alkylammonium cations (e.g. 20, Scheme 21) [30]. In aqueous media, the quaternary ammonium groupings promote the reactivity of organic anions which presumably bind in high concentration to the polycationic periphery of the dendrimer. The latter species enhances the rate of the bimolecular hydrolysis of p-nitrophenyl diphenyl phosphate catalyzed by o-iodosobenzoate ion. 

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). 

Figure 17 illustrates a typical decarboxylation experiment with nitro-benzisoxazole carboxylate under conditions of C S (curve A). With... 

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... 

One method of synthesis of 1,2-benzisoxazoles involves cyclization of o-halo- or o-nitro-benzoyl oximes via intramolecular SNAr.167 168 A recently reported variant, which gives access to sterically constrained 3-phenyl-1,2-benzisoxazoles, employs a reversed sequence of steps, e.g. nucleophilic... 

The potential of these dendrimers for unimolecular decarboxylation of 6-nitro-benzisoxazole and o-iodobenzoate-catalysed bimolecular hydrolysis of p-nitrophe-... 

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