Preparation of Aryl Azides

The most interesting TV-coupling reaction of this subsection is that with azide ions, which has been known since the end of the last century. This reaction is frequently used for the preparation of aryl azides. Two examples can be found in Organic Syntheses (Smith and Boyer, 1963 Mendenhall and Smith, 1973). As Scheme 6-20... 

The most frequent synthetic approaches, summarized in Scheme 4, are towards the primary photophores. The preparation of aryl azide derivatives follows the typical retro-synthetic pathway in the majority of the reported cases (Scheme 4 A), and, practically, diazotation is the most commonly used procedure [24 - 29]. In the case of diazirines only one major synthetic sequence is repeated ammonolysis of oximes followed by dehydrogenation (Scheme 4B) [30-32]. There are various ways of preparing diazo- or diazocarbonyl-compounds most frequently the Forster and Bamford-Stevens reactions (Scheme 4C) are employed [33-37]. 

Preparation of Aryl Azides. Aryl azides may be prepared by reaction of aryl carbanions with tosyl azide followed by treatment of the triazene salt with sodium pyrophosphate (Eq. 67)305 or aqueous base (Eq. 72).315... 

The hazardous nature (see Tetrazoles below) of some alkyl azides limits the method in these cases, however A-alkyl- (benzyl) -1,2,3-triazoles can be obtained by preparing the azide in situ, for example using a mixture of sodium azide, the alkyne and a benzyl hahde in situ preparation of aryl azides is also feasible. An alternative method in which the alkyl azide is also generated in situ, is to use a diazo transfer to a primary amine the diazo transfer requires Cu(II) and the cycloaddition needs Cu(I) so a reducing agent is added together with the alkyne following the first phase. ... 

Organic azides. A method for the preparation of aryl azides from arylamines consists of reaction with t-BuONO and MesSiNs in MeCN. ... 

Preparation of Aryl Azides Through sp C-H Bond Azidation... 

Telvekar VN, Sasane KA (2012) Simple and eiScient method for the preparation of aryl azides using sonication. Synth Commun 42(7) 1085-1089... 

The Siindberg indole synthesis using aromadc azides as precursors of nitrenes has been used in synthesis of various indoles. Somekmds of aryl azides are readily prepared by S Ar reacdon of aromadc nitro compounds v/ilh an azide ion. For example, 2,4,6-trinitrotoliiene (TNT can be converted into 2-aryl-4,6-dinitroindole, as shovmin Eq. 10.60. ... 

The thermal, and more importantly, the photolytic decomposition of aryl azides in the presence of nucleophiles, generally amines or alcohols, is the commonest method for preparing 3H-azepines. In fact, jV-phenyl-3//-azepin-2-amine (32, R = Ph), the first example of a 3//-azepine, was prepared by thermal decomposition of phenyl azide in aniline.32... 

The thermolysis of aryl azides in alcoholic solution has been used to prepare 2-alkoxy-37f-azepines. Thermolysis of 3-azidophenyl methyl ketone in methanol in a sealed ampule furnishes a mixture of the 6-acetyl- (36a) and 4-acetyl-2-methoxy-3//-azepine (37a) in superior yields to those obtained in the corresponding photolytic reaction.78 Other 3-substituted azides behave similarly, with a preference for the 6-substituted isomers 36, as is observed for azide photolyses in amine solutions. 

Nucleophilic displacement of the butoxy group in 2-butoxy-3//-azepine (1) by the use of excess secondary amine is preferred by some workers64 to the photolysis or thermolysis of aryl azides, or the deoxygenation of nitro- or nitrosoarenes in amine solution, as a preparative route to Ar,Ar-dialkyl-3//-azcpin-2-amines, e.g. 2,... 

Other iron-imido complexes have also been reported. Holland and coworkers reported the synthesis of the imidoiron(III) complex [L FeNAd] [40, 41]. This imidoiron(III) complex has not been isolated and was found to convert to a purple high-spin iron(III) complex. It has an S = 3/2 ground state from EPR measurement. Based on the results of QM/MM computations, [L EeNAd] is a three-coordinated complex with an Fe-N distance of 1.68 A and has a nearly linear Fe=N-C unit with Fe-N-C angle of 174.1°. Chirik and coworkers made use of liable ligands to prepare iron-imido complexes by treatment of C PDI)-Fe(N2)2 ( PDI = (2,6- Pr2CgH3N = CMe)2C5H3N) with a series of aryl azides [47]. 

Other approaches to tetrazoles were also recently published. Primary and secondary amines 195 were reacted with isothiocyanates to afford thioureas 196, which underwent mercury(II)-promoted attack of azide anion, to provide 5-aminotetrazoles 197 . A modified Ugi reaction of substituted methylisocyanoacetates 198, ketones, primary amines, and trimethylsilyldiazomethane afforded the one-pot solution phase preparation of fused tetrazole-ketopiperazines 200 via intermediate 199 <00TL8729>. Microwave-assisted preparation of aryl cyanides, prepared from aryl bromides 201, with sodium azide afforded aryl tetrazoles 202 . 

The microwave-assisted preparation of aryl tetrazoles 179 was reported using the intermolecular 1,3-dipolar cycloaddition of aryl nitriles 178 with sodium azide (38) (Scheme 9.38). 

Historically the first fully unsaturated azepine was obtained by Wolff in 1912 by the decomposition of phenyl azide in aniline. However, the actual structure of this product, named dibenzamil , remained unknown until 1955, when Huisgen and coworkers showed it to be an anilinoazepine, originally formulated as the 7-anilino-2H-azepine, but later corrected, mainly on the basis of HNMR evidence, to the 2-anilino 3H-tautomer (221 R1=PhNH R2 = H). Subsequently, the thermolysis and photolysis of aryl azides in primary, secondary and, in certain instances, tertiary amine solution has become a standard method for the preparation of 2-amino-3/f-azepines (79AG(E)900,8lAHC(28)23l). 

More convenient is the use of aryl azides which are readily converted into isocyanates upon heating in nonreactive solvents via the loss of nitrogen. The latter method is useful for the synthesis of isocyanates with additional substituents which could not be prepared with phosgene (20). 

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... 

Scheme 2 Preparation and examples of aryl azides, (a) Three possible routes for the conversion of an aryl amine into its aryl azide (i) via diazotization [44], (ii) by the use of triflyl azide [45], and (iii) with sulfonyl azides 15 (R = imidazole [46] or R = benzotriazole [55]). (b) Examples of substituted aryl azides...

Lamara, K. and Smalley, R.K. (1991) 3H-Azepines and related systems. Part 4. Preparation of 3 H-azepin-2-ones and 6 H-azepino[2,l-b]quinazolin-12-ones by photo-induced ring expansion of aryl azides. Tetrahedron, 47 (12/13), 2277-2290. 

Dihydrotriazoles were prepared diastereoselectively by cycloaddition of aryl azides to enol ethers and, under controlled conditions, enamines6-7. In only a few cases were the aziridines prepared by photochemical decomposition of thus formed dihydrotriazoles 84-85. 

The reaction of aryl azides with excess alkenes in the presence of trifluoroacetic acid proceeds by an analogous mechanism and afforded, after basic hydrolysis, /5-hydroxy amines together with byproducts. A diastereoselective reaction was observed only with cyclic and acyclic (Z/-alkenes, e.g., 12 and 1388. From methyl ( )-2-butenoate, A-phenylthreonine methyl ester was similarly prepared in 30% yield88. 

Azides undergo decomposition upon treatment with strong concentrated acids, one of the main products being primary amines. The reaction of aryl azides with concentrated sulphuric acid yielded complex mixtures , probably because of nucleophilic attacks on the positively charged intermediates. Amines could be isolated in low yields only, and the reaction has no real preparative value. 

In an interesting technique for the preparation of aromatic azides, aryl diazonium salts are treated with azide ions." "" At least in a very formal sense, one can consider this reaction as a substitution process, although the real mechanism of this transformation is much more complicated. An excellent... 

In contrast to the N-MEM (N-alkyl) analogue (see Sect. 2.2.2), N-aryl-aza-fiilleroids, obtained from the thermal reaction of aryl azides with 50, can be photochemically isomerized to azirenofullerenes [51]. This closely resembles the difference in the photochemical behavior of C-aryl- and C-alkyl fulleroids obtained from the reaction of diazo compounds with Qo (e.g. [5,6] CgiHj is photochemically stable). After some initial studies (see for example [52-55]), the addition of azides and nitrenes to C o has been investigated and used for the preparation of a series of functional fullerene derivatives by a number of other investigators, but their work is not relevant in relation to the preparation of aza[60] fullerene. The addition of azides to fullerenes has been brie% reviewed previously [56-58]. 

Recently, Bandgar and Pandit have described a mild, efficient, and general method for the preparation of acyl azides from carboxylic acids and sodium azide using CC (Scheme 47). Various aryl, heteroaryl, alkylaryl, and alkyl carboxylic acids, on reaction with CC in the presence of sodium azide and A -methylmorpholine, undergo smooth conversion to the corresponding acyl azides in excellent yields <2002TL3413>. 

The present chapter is not intended to be a catalogue of all aspects of azepine chemistry which have been published since CHEC-I. Thus, for example, many established areas such as the Beckmann and Schmidt reactions for the preparation of reduced azepines are discussed only in respect to newer developments. The Beckmann rearrangement has been reviewed <870R(35)i>. The emphasis is to take forward the knowledge of azepine chemistry, to describe new chemistry and to develop earlier aspects which were just emerging when CHEC-I was being prepared. Such aspects include the synthesis and properties of azepine-3(2//) Ones, the formation of bicyclic and tricyclic azepines by the cyclization of diene-conjugated nitrile ylides and those results since 1984, theoretical and experimental, on the mechanism and synthetic applications of aryl azide chemistry. 

In 1951, Smith and Brown were the first to show that the photolysis of aryl azides led to carbazoles (Scheme 17, equation 1) [114], a reaction that also occurs upon heating. Other carbazoles so prepared are 36 to 39. This reaction has been reviewed [115-119], and has been of more interest mechanistically than synthetically, by the groups of Reiser [120, 121], Swenton [122-124], Berry [125], Sundberg [126, 127], Yabe [128-130], Meth-Cohn [131], and Spagnolo [132]. Sundberg provides an excellent summary of the possible mechanisms involved in the photolysis of 2-azidobiphenyl to carbazole [126, 127], and his own work indicates that a triplet nitrene may not be the sole or major carbazole precursor [127]. In any event, the photochemical transformation of aryl azides is a useful synthesis of carbazoles. Some additional examples are shown in Scheme 17 [114, 115, 124, 128, 129, 133]. In addition, Sauer and Engels obtained, as expected, a nearly 1 1 ratio of 1- and 3-methylcarbazoles (85%) on photolysis of 2-azido-3 -methylbiphenyl [134]. 

Small amounts of water act in synergy with sonication and solid-support catalysis, for instance, in the reaction of thiocyanate ions. As in the previous case, presonication of the reagent and the support was found to improve the selectivity. These methods permit the substitution reactions to be run even in apolar solvents. Two practically simultaneous papers have described the preparation of aryl sulfones by alkylation of sodium arylsulfinates with reactive alkyl chlorides.i The reaction with benzyl chlorides is best performed on alumina, and allyl bromide reacts quantitatively in a DMF-water mixture in a few minutes. Activated primary halides undergo substitution by sodium azide in aqueous solution to give the potentially explosive organic azides. 1 The paper discusses the possible role of the relative densities of the starting material, the aqueous solution of the reagent, and the product in the success of the preparation. 

Azide additions to a,P-unsatnrated systems are another method for the preparation of 1,2,3-triazoles. Cydoaddition of aryl azides to a,P-unsaturated aldehydes 88 in the presence of catalytic diethylamine and DBU afforded 1,4-disubstituted-l,2,3-triazoles 89 via an inverse electron-demand process (13CC10187). Michael addition of sodium azide with ethyhdene bisphospho-nates 90 in cydoaddition reactions via sonication afforded bisphosphono-1,2,3-triazoles 91 (13T4047).A one-pot protocol for the synthesis of 1,2,3-triazoles was prepared from unactivated alkenes with azidosulfenylation of the carbon-carbon double bond followed by the copper-catalyzed azide—alkyne cycloaddition (13JOC5031). 1,5-Disubstituted-l,2,3-triazoles 93 were synthesized from enamides 92 with tosyl azide (13AG(E)13265). Reaction of ethyl 3-(alkylamino)-4,4,4,-trifluoro-but-2-enoates 94 with mesyl azide in the presence of DBU afforded l,2,3-triazole-4-carboxylates 95 (13EJ02891). 

The in situ preparation of aryl and heteroaryl azides from the corresponding aryl halides via L-proline-promoted Cnl-catalyzed coupling reactions in the presence of alkynes allows the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles (e.g. 226). Liang et al. also reported the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles (e.g. 227) from aryl bromides or iodides and terminal alkynes in the presence of sodium azide using diamine-promoted Cnl-catalyzed reactions. It has also been shown that this type of synthesis can be carried out in a mixture of the ionic liquid [bmim][BF4] and water (Scheme 3.32). Starting with boronic acids, the catalytic approach to aryl azides and l-aryl-1,2,3-triazoles can be carried out under milder reaction conditions and improved substrate tolerance (Scheme 3.33). In fact, it was demonstrated that both electron-rich and electron-poor aryl boronic acids 228 could be efficiently converted into the corresponding aryl azides (229) in the presence of sodium azide and CUSO4. A one-pot protocol... 

---