Nitrene-Induced Cyclizations

Pyrolysis of an azide frequently produces the reactive nitrene, which immediately attacks a nearby position on an adjacent ring. The azide is usually heated in an inert high-boiling solvent, although cyclization may occur without a solvent. Photochemically induced cyclization of an azide can often give a good yield of product. 

A comparison of several base-induced cyclizations of 2-acylbenzazides by several bases showed that ethanolic potassium hydroxide at room temperature was an efficient process. Some evidence is available that nitrogen loss assisted by an enolate ion rather than nitrene formation occurs under these conditions. 

The products from the thermolysis of anthranils bearing a heteroaryl residue at position 3 are less predictable. 3-(2-Pyridyl)anthranils in boiling trichlorobenzene yield pyrido[l,2-h]cinnolin-6-iums (e.g., 139) (cyclization of the initially formed nitrene taking place only at the electron-rich nitrogen center) and no rearranged products.191 In contrast, the 3-(2-imidazolyl)-anthranil 108 (X = N, Y = CH) yields a mixture of the nitrene-induced rearrangement product (157) (63%) and the nitrene insertion product (158) (3%).131 The 3-(5-pyrazolyl)anthranil 108 (X = CH, Y = N) behaves similarly. 

In accordance to that, the described transformation can be further generalized as a nitrene-induced aromatic rearrangement, possessing the ability to prepare several cyclized heteroaromatics such as phenothiazines, phenoxazines, and dibenzooxazepines. ... 

In contrast to carbenes, nitrene attacks only the carbon and never the sulfur atom of thiophene the only exception to this is discussed in Section 3.14.3.5. Unsubstituted thieno[3,2-/>]pyrrole and thieno[2,3-6]pyrrole have been prepared by thermolysis of the corresponding vinyl azides (Scheme 68) (81IJC(B)27l). A bis-cyclization of this type has also been reported (73CR(C)(277)1149>. Similarly, in the benzo[Z>jthiophene series the nitrene (252), generated either by thermolysis of the azide or by P(OEt)3 induced deoxygenation of the nitro compound, gives only the condensed indole (253) (79AG(E)900). 

Activated copper powder or copper(II) acetylacetonate were effective catalysts in the pyrolytic cyclization of 2-azido-3-(2,4-pentadienyl)-l,4-quinones to benzopyrolizines 17 by the presumed intermediacy of a copper(II)-nitrene species which adds to the diene by a radical pathway. Although the yields were generally low, complete regioselectivity and diastereoselectivity (simple and substrate induced) were observed152. 

The formation of benzimidazoles by cyclization of aryl amidines can be accomplished in a number of ways, but is usually carried out under anhydrous conditions in the presence of a base. Thus cyclizations of (45 R = OH) induced by benzenesulfonyl chloride in pyridine or triethylamine generally give yields of greater than 60%. The more direct process of oxidizing the parent compounds (45 R = H) with sodium hypochlorite under basic conditions gives even higher yields (70-98%). Intermediates in these reactions are the )V-haloamidines (45 R = C1) a nitrene intermediate may be involved or merely dehydrochlorination with concomitant cyclization (Scheme 25). Alternative cyclization procedures include oxidation of the parent amidines (45 R = H) by manganese dioxide or lead tetraacetate and thermal... 

The mechanism of the photochemically induced conversion of vinylazides into 2H-azirines has been examined using ab initio MO calculations. A new approach to the elusive thionitrosobenzene system has been reported. Direct irradiation of the 3-azido-2,l-benzisothiazole (88) affords a transient 2-cyanothionitrosobenzene (89) which can be trapped as the cycloadduct (90) with cyclopentadiene. Nitrene cyclization is the preferred pathway on irradiation of the 5-formyl- or 5-benzoyl-6-azidouracils (91) and yields the isoxazolo[3,4-d]pyrimidines (92). In contrast, 5-phenyl- and 5-benzyl-6-azidouracils were converted into pyrimido[4,5-b]indoles and pyrimido[4,5-ti Jquinolines, respectively, by a pathway involving photochemically induced loss of nitrogen and intramolecular nitrene insertion. 

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