4-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. 

Enamines from cyclic ketones give derivatives of triazole 133,134). The enamine (113) reacts with p-nitrophenyl azide to give the triazoline (194), which on treatment with acid gives the triazole (195). 

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, ... 

The diethylketal of A -methylpiperidone or 3,4,5,6-tetrahydropyridines add to 4-nitrophenyl azide to give respectively compounds 113 (86CB3591) and 114 (86AP(319)1049). For compound 113 elimination of ethanol gives the tetrahy-drotriazolopyridine. 

Benzofuroxan 79 can be generated from 2-nitrophenyl azide 80 (Scheme 49). Neighboring-group assistance within the pyrolysis leads to a one-step mechanism with an activation barrier of 24.6 kcal/mol at the CCSD(T)/6-31 lG(2d,p) level [99JPC(A)9086]. This value closely resembles the experimental one of 25.5 kcal/mol. Based on the ab initio results for this reaction, rate constants were computed using variational transition state theory. 

The yield of 3//-azepine appears to be influenced by substituents on the azide ring although no in-depth study has been reported. 4-Halophenyl azides, in most cases, give rise to complex mixtures of products.177 4-Tolyl azide, on thermolysis in aniline, yields 5-methyl-iV-phenyl-3//-azepin-2-amine (18% mp 157-158°C), whereas the thermolyses of 4-methoxy-, 4-methyl-, 4-chloro-, and 4-nitrophenyl azides in a range of arylamines (4-chloro-, 4-methoxy-, and pen-tafluoroaniline) yield only azo compounds and uncharacterized tarry products.178... 

Magnoli, A., C. Mariani, and M. Simonetta Crystal, Molecular, and Electronic Structre of p-Nitrophenyl Azide. Acta Crystallogr. [Copenhagen] 19, 367 (1965). 

Esters of 1,2,3-triazolecarboxylic acids are the most common derivatives of triazole (Section 5.01.9) therefore, their conversions to other, more useful, functionalities are of great importance. In an example given in Scheme 48, 4-triazolecarbocylic ester 317, obtained from a reaction of (3-ketoester 316 with 4-chloro-2-nitrophenyl azide, is hydrolyzed to free acid 318 (82% yield) by 4% KOH. Heated to reflux in DMF for 3 h, acid 318 undergoes decarboxylation to triazole derivative 319 with 81% isolated yield <2004FA397>. 

Phenyl azide reacts slowly with bis(trimethylsilyl)butadiyne at elevated temperature to give 1,2,3-triazole (718) as the only product. Similar reaction of 4-nitrophenyl azide and bis(trimethyl-... 

The triazole ring can be synthesized by reaction between a suitable pyridine (or piperideine) and an azide. Thus 5-nitro-2-pyridone (or N-substituted pyridones) and sodium azide give a 5-oxotriazolo[4,5-b]pyridine (94)182-184 whereas the enamine 95 reacts with p-nitrophenyl azide to give the hexahydro-l//-triazolo[4,5-c]pyridine 96.185,186... 

The characteristics of the 1,3-dipolar cycloaddition mechanism of azides and other 1,3-dipoles (such as diazoalkanes, azo-methine imines, nitrones, nitrile imines, nitrile oxides) have been described in detail by Huisgen.191 19 According to the author, the addition of a 1,3-dipole (a b c) to a dipolarophile (d e) occurs by a concerted mechanism in which the two new a bonds are formed simultaneously although not necessarily at equal rates (32). As a consequence, a stereoselective cis addition is observed. Thus, the addition of p-methoxyphenyl azide to dimethyl fiynarate (33) yields l-(p-methoxyphenyl)-4,5-froiw-dicarbomethoxy-AMriazoline (34),194 and 4-nitrophenyl azide gives exclusively the respective cis-addition products 35 and 36 on addition to irons- and cis-propenyl propyl ether.196... 

Enamines contain electron-rich double bonds and thus react readily with azides (in many cases at room temperature). Only one addition product is formed, namely a 5-amino-A2-triazoline, a result of electronic control.22 -223 Thus l-(p-nitrophenyl)-4-ethyl-5-morpholino-A2-triazoline (44) arises from the addition of p-nitrophenyl azide to 1-morpholino-l-butene (43). The addition products rearrange by heating into amidines (45).224... 

The addition reactions of aryl azides onto enamines bearing a carbonyl, sulfonyl, or nitro group in the 0 position with respect to the nitrogen atom have been investigated by Italian authors.240-241 The expected triazoline derivatives could not be isolated but were immediately converted into the corresponding 1,2,3-triazoles (49) and secondary amines. The reaction of p-nitrophenyl azide with l-benzoyl-2-morpholino-l-propene (48) is given as a typical example. 

Organic azides combine with open-chain and cyclic eno) ethers to give A -triazolines in high yield. The addition is stereospecific cis and the orientation process is determined by electronic effects.145-160 The triazolines are unstable above 100° and can decompose in mainly two ways. 44 Triazolines from the open-chain enol ethers, vinyl butyl ether, /S-ethoxypropene, and a- and /3-methoxystyrene, eliminate alcohol thermally and are converted into 1,2,3-triazoles. For example, the triazoline 67 from /J-ethoxypropene 66 and p-nitrophenyl azide decomposes quantitatively at 150° into l-(p-nitrophenyl)-5-methyl-1,2,3-triazole (68). 

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-... 

Orientation of addition is in accordance with general mechanistic considerations for 1,3-dipolar cycloadditions, and is highly regioselec-tive.27,34,40,171-174 The addition of p-nitrophenyl azide to styrene, however, is an exception the triazoline (21) and an aziridine obtained from thermolysis of the isomeric triazoline (20) are the products (Scheme 27).110,175... 

In an analogous manner, 9-methylene- and 9-benzylidenefluorenes react with excess aryl azides to give spirofluorenetriazolines (29) in 25-56% yields (Scheme 36) with p-nitrophenyl azide, only the ring-enlargement product is obtained.194... 

Triazolines obtained by the addition of aryl azides to enamines are generally isolable and a considerable number of triazoline compounds have been prepared in this way (Scheme 45.)208,209 Although usually nitrophenyl azide is used, because electron-withdrawing groups on the azide facilitate addition,28,42 diethylaminophenyl azide also works satisfactorily (Scheme 46).209... 

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>. 

In contrast to benzenesulfonyl azide, the reaction between 8 and aryl azides gives only a small amount of 226. Instead, highly substituted triazoles 228 are formed as the major products176,177. When 4-nitrophenyl azide is used, the reaction furnishes 228 exclusively. It has been believed that the reaction involves two competitive pathways and benzoyl-substituted 1,1-enediamines 8 act mainly as nucleophiles rather than as 1,3-dipolarophiles toward aryl azides. Consequently, they add to the azide group and, following intramolecular cyclocondensation, give products 228. Only in the case of unfavorable electronic factors does 1,3-cycloaddition reaction to give 226 take place (Scheme 13)177. 

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