Isatogens

Pfitzinger synthesis, 2, 446 six-membered heterocycles from, 2, 92 synthesis, 4, 150 Isatogens... 

Cyclization of o-nitroacetylenylbenzenes and cyclocondensation of o-iodonitrobenzene with copper acetylides are widely used to produce isatogens [69JCS(C)2453 69MI2 79JHC221]. The nitro group can be either in the acetylide or in the halide components. 

Whereas the condensation of o-iodonitrobenzene with copper acetylides is accompanied by cyclization into isatogens, neither 4-iodo-3-nitro- nor 5-iodo-4-nitro-l,3-dimethylpyrazole gives cyclized products in conditions of acetylide synthesis. Moreover, nitropyrazolylphenylacetylene, as compared with o-nitrotolane, does not undergo thermal, catalytic, or photochemical isomerization to give the fused five-membered rings. 

Isatogens (1) and indolones (2) are brightly colored solids that do not occur naturally. Isatogens (I) are more comprehensively named as 3-oxo-3//-indole 1-oxides, or as the 1-oxides of indolones (2), 3-oxo-3H-indoles, or 3//-indol-3-ones. Both series of compounds are numbered in accordance with IUPAC rules. Isatogens were first reported in 18811,2 and the first indolone in 1912.3 Isatogens (1), indolones (2) and indoxyls (3) form an interrelated redox system. Indolones in which there is a methylene or methine substituent in the 2-position tautomerize to the preferred 2-methylene-3//-indol-3-one (indogenide) structures (4).4 Only passing reference will be made to 3 and 4 in this review. 

Isatogens, last reviewed in 1954,5 are usually represented as 1, but they are more fully described by the additional canonical structures 5-7. The addition of nucleophiles and some dipolarophiles is indicated by 5... 

Isatogens may be prepared by two general methods involving either an intramolecular cyclization or oxidation of a 2-substituted indole derivative. 

Until very recently, most syntheses of isatogens were in this category and characteristically involved ortho-substituted nitrobenzenes. 

The cyclization of 2-nitrophenylacetylene derivatives (8) provides a versatile route to isatogens bearing mainly aryl,5 7 arylcarbamyl,8 or alkoxycarbonyl1 2,9,10 substituents in the 2-position. Four different reagents have been used to effect this type of cyclization. 

Castro and Stephens16 developed a method for the preparation of unsymmetrical disubstituted acetylenes, which involves the reaction of copper(I) acetylides with aromatic iodo compounds. Bond and Hooper7 extended this route to the preparation of 2-arylisatogens (22). 2-Nitro-phenylpropiolic acid (19a) is readily decarboxylated to the acetylene (19b), which on treatment with copper(I) chloride gives 19c. The reaction of 19c with substituted aromatic iodo compounds (20) gives the corresponding acetylenes (21), which subsequently cyclize to the isatogens (22). The alternative route (23 + 24 - 21) has been little used.17... 

The influence of steric factors is indicated by the fact that the intermediate tolans are isolable only when ortho substituents are present (21 R = ortho substituent). In all other cases cyclization to the isatogen takes place under the reaction conditions. The tolans (21 R = ortho substituent) are usually cyclized by further heating in pyridine. In more difficult cases, cyclization requires irradiation of a pyridine solution or heating under reflux with nitrosobenzene in chloroform solution (Section II,A,l,d). 

The attempted reaction of 4-iodobenzoic acid with 19c did not yield the expected tolan or isatogen. Only trace amounts of anhydroisatin-cr-anthranilide (37) and the indolinone 38 (Section II,A,l,d) were isolated.7 Both these products arise from the reactions of two molecules of I9b, which would be formed by the action of acids on I9c. Athough 37 was unequivocally identified, it is difficult to propound a reasonable mechanism for its formation. 

The intramolecular cyclization of a nitro group with a triple bond has been extended to the synthesis of six- and seven-membered ring compounds analogous to isatogens. Thus, the reaction of the acetylene group with the nitro group in 39 yields 2-phenyl-3-oxobenzo[prepared from the corresponding biphenyl derivative.19... 

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