O-Nitrophenyl azide

Perhaps one of the most exciting developments in the chemistry of quinoxalines and phenazines in recent years originates from the American University of Beirut in Lebanon, where Haddadin and Issidorides first made the observation that benzofuroxans undergo reaction with a variety of alkenic substrates to produce quinoxaline di-AT-oxides in a one-pot reaction which has subsequently become known as the Beirut reaction . Many new reactions tend to fall by the wayside by virtue of the fact that they are experimentally complex or require starting materials which are inaccessible however, in this instance the experimental conditions are straightforward and the starting benzofuroxans are conveniently prepared by hypochlorite oxidation of the corresponding o-nitroanilines or by pyrolysis of o-nitrophenyl azides. 

Benzofuroxan may be obtained by oxidation of o-quinone dioxime. The first benzofuroxan derivative, 1,2-naphthofuroxan, was obtained by this method. Suitable oxidizing agents include alkaline ferri-cyanide, bromine water, chlorine, and nitric acid. The method is of practical value only when the o-quinone or its monooxime (o-nitrosophenol) is readily available, and since this is not generally the case, other routes, e.g., the oxidation of o-nitroanilines and the thermal decomposition of o-nitrophenyl azides/ are more commonly used. 

The most reliable method of preparing benzofuroxans is by decomposition of o-nitrophenyl azides. Decomposition can be achieved by irradiation, or more usually by pyrolysis temperatures between 100° and 1.50° are commonly used. Refluxing in glacial acetic acid is the recommended procedure for 4- or 5-sub-stituted 2-nitrophenyl azides, but with 3- or 6-substituted compounds higher boiling solvents are usually necessary. Quantitative studies on the reaction rate have been made, and a cyclic transition state invoked, an argument which has been used to account for the greater difficulty of decomposition of the 6-substituted 2-nitrophenyl azides. Substituent effects on the reaction rate have also been correlated with Hammett a constants, ... 

As well as the previous chapter on the Hammett equation,1 the importance of the approach has found expression in specific areas in other contributions to these volumes side chain reactivities of thiophenes 17 tautomerism 18 reactions of azines with nucleophiles 19,20 formation of benzofuroxans by decomposition of o-nitrophenyl azides 21 acid dis-... 

The generation and reactions of arylnitrenes continue to attract attention. Evidence for a photoinitiated autocatalytic chain mechanism in the photodecomposition of phenyl azide has been reported, and the reaction of photochemically generated phenyl nitrene with oxygen has been reexamined. Irradiation of p-azidoaniline in aqueous solution yields triplet p-aminophenyl nitrene, which on reaction with water is converted into the highly reactive p-benzoquinone diimine. Both m- and p-nitrophenyl azides, on photoelimination of nitrogen at 77 K, afford the corresponding nitrenes, whereas o-nitrophenyl azide (93) is converted without the intermediacy of a nitrene into the benzofurazan (94). 4,4 -... 

The thermal decomposition of sulfonyl azides, like azido formates, appears to involve nitrene intermediates . The thermolysis of benzenesulfonyl azide is first order and the rate coefficient is relatively insensitive to solvent changes or substituent effects . o-Nitrobenzenesulfonyl azide decomposes with evolution of nitric oxide and nitrogen the rate of azide disappearance however, is about the same as that for other benzenesulfonyl azides and it appears that the reaction leading to NO can be explained by an intramolecular rearrangement in the nitrene intermediate. This is in contrast to the decomposition of o-nitrophenyl azide (vide infra) where rearrangement occurs in the transition state of the rate-determining step. 

There are many cases where a suitable ortho substituent assists in the elimination of nitrogen and no nitrene is formed. It is characteristic of these reactions that they have a lower activation energy than those in which nitrenes are formed, and consequently the decompositions occur at significantly lower temperatures. For example, o-nitrophenyl azide (165) decomposes at 65-90° to benzofuroxan (166) whereas... 

The classical photochemical reaction of Ciamictan and SUber (153) of o-iRltrobenzaldehyde transformed into o-nitrosobenzoic add is described in the thipter on photochemistry of nitro compounds. o-Nitrophenyl azide can readily yield benzofuroxane [154]. 

Evidence for nitrene intermediacy comes from kinetic analyses that show reactions of this type to be strictly first order in aryl azide. Thermolysis of aryl azides in more reactive solvents, which contain an olefmic double bond, does not involve the intermediacy of a nitrene. A kinetic study of the thermolysis of p-anisyl azide in indene indicated a concerted loss of nitrogen and no evidence could be found for the formation of a triazoline. This is surprising as azides are well known to add to olefins to give triazolines in other systems. Loss of nitrogen without nitrene involvement is also observed in the decomposition of aryl azides bearing certain o-substituents (e.g., nitro, phenylazo, and carbonyl or thiocarbonyP ) for instance, thermolysis of o-nitrophenyl azide gives benzofuroxan ... 

Recently, very fast intramolecular cyclization of singlet nitrene was observed upon photolysis of ort/ o-nitrophenyl azide (76). It is well known,that pyrolysis and photolysis of 76 leads cleanly to benzofuroxan (77). According to the results of recent computational stud) and early experiments, the pyrolysis of 76 produces 77 by a concerted one-step mechanism. However, photolysis of 76 produces 77 through a stepwise mechanism. Formation of singlet nitrene 78 from excited 76 was detected to occur with a time constant 500fs. The lifetime of nitrene 78 is very short - 8.3ps, and corresponds to ring-closure reaction rate constant 1.2 x 10" s. ... 

Azides [e.g. (+)-neomenthyl azide no physical data reported] are formed efficiently by inversion, from the corresponding alcohols and diphenylphosphoryl azide, in the presence of triphenylphosphine and diethyl azodicarboxylate [which has also been used for esterification with inversion (Vol. 5, p. 334) for a related esterification of (—)-menthol see ref. 119] a conceptually similar synthesis also yields (+)-neomenthyl azide. Cyanoselenenylation of aldehydes and of alcohols has been reported thus treatment of geraniol with o-nitrophenyl seleno-cyanide-Bu sP-THF yields the selenide (19) which can be converted into the... 

AMIDES Bis(o-nitrophenyl)phenyl-phosphonate. N,N-Bis(2-oxo-3-oxazoli-dinyl)phosphordiainidic chloride. 2-Chloro-2-oxo-l,3,2-bcnzodioxa-ph05-phole. Iodine azide. N-Methyl-N-phenyl-benzohydrazonyl bromide. Phase-transfer catalysts. N-Phenylseleno-phthalimidc. (SEProlinol. 

A study of ketene A, O-acetals has shown that such compounds derived from lactam acetals may be used in the preparation of larger heterocyclic systems via reaction with a 1,3-dipolar species, the initial cycloadducts stabilizing their structures by aromatization. Pyrrolo[2,3-i/]-l,2,3-triazole derivatives, however, do not undergo such elimination reactions and stable cycloadducts may be obtained. Thus, the lactam acetals (133) give the ketene A,0-acetals (134), which on reaction with p-nitrophenyl azide yield substituted pyrrolo[2,3-d]-l,2,3-triazole derivatives (135) <86CB359l>. 

The dibenzo derivative (181) has been obtained by cyclization of o-nitrophenyl-2//-benzotriazole (180 R=N02) using triethyl phosphite (67JA2633) or by thermolysis of the corresponding azide (180 R = N3) (67JA2618). 

The dibenzo heterocycle (183) has been prepared by methods analogous to those used for the isomeric system (181). Cyclodeoxygenation of o-nitrophenyl-liT-benzotriazole (182 R = N02) using triethyl phosphite gives the colourless crystalline heterocycle (183) which is also formed by thermolysis (180 °C) of the azide (182 R = N3) (67JA2618, 67JA2633). Monobenzo derivatives have been similarly prepared (67JA2633). 

A further example of the diminished significance of the decomposition pathway for nitroaromatic azides is implicit in the observation of Bailey and White that whereas phenyl azide is an unsuitable starting material in the synthesis of picryl azide, both o- and p-nitrophenyl azide react smoothly in a mixture of nitric and sulphuric acids at low temperature to yield the jym-trinitro derivative. 

A number of cyclopropyl-substituted five-membered heterocycles have been synthesized by addition of various 1,3-dipolar reagents to (alk-l-enyl)cyclopropanes. Most reactions were performed using tricyclo[3.1.0.0 ]hex-3-ene and tricyclo[3.1.0.0 ]hex-3-en-3-yl phenyl sul-fone, giving the corresponding cycloadducts in very good yields on treatment with azides, a carbonyldicobalt complex, nitrile oxides, diphenylni-trilimine, (4-nitrophenyl)benzenecarbonitrile ylide, and diazoalkanes. For example, addition of tricyclo[3.1.0.0 ]hex-3-ene (1) to 4-nitrophenyl azide gave dihydro-1,2,3-triazole 2 in 94 /o yield. ... 

The first report of the preparation of quinoxaline di-N-oxides from benzofuroxans was by reaction with enamines. Benzofuroxans are themselves conveniently prepared by oxidation of the appropriate o-nitroanilines with hypochlorite or by pyrolysis of the corresponding nitrophenyl azides. A variety of enamines react satisfactorily, but the less reactive morpholine enamines give higher yields and more easily isolata-ble products (Scheme 5). " ... 

A variety of preactivated acyl derivatives has been developed for peptide bond formation. These include acyl halides [chlorides [66], fluorides [67,68]], acyl azides [69,70], active esters [e.g., pentafluorophenyl (OPfp) [71], o-nitrophenyl (ONp) [72], 3,4-dihydro-4-oxo-l,2,3-benzotriazin-3-yl (ODhbt) [73]], mixed anhydrides [3], and symmetrical anydrides [74,75]. 

Thermolysis of aryl azides in acetic anhydride gives AT,0-diacetyl-o-aminophenols plus some triplet-derived products. Yields are good for azides bearing methyl or halo substituents, but nitrophenyl azides do not undergo this reaction ... 

---