Nitrenes azides

The effect of annelation seems to be a lowering of the activation energy for ring contraction in the nitrenes azides 168 and 175 contract more easily than phenyl azide (cf. Table 19). The fact that 167 and 173 do give ring contraction products reaffirms the statement that triazoles do not pyrolyze by a mechanism fundamentally different from that of the tetrazoles (p. 232). 

Azido compounds are versatile molecules. They are used extensively in both organic reactions and chemical biology. All azides are potentially explosive and must be handled with care. Azides, which have been known for over 100 years, are the most widely used precursors of nitrenes. like diazo compounds, they possess a linear 1,3-dipolar stracture and are easily prepared, often by introduction of the azide (Nj ) ion from inorganic salts such as sodium azide. The thermal stability of azides is critically dependent on the substituent on nitrogen. Most azides decompose thermally in the range 100-200 °C to give nitrenes. Azides are also readily decomposed photochemically, and this is often the method of choice, particularly for mechanistic studies. Like diazo compounds, the decomposition of... 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Sulfonic acid hydrazides, RSO2NHNH2, are prepared by the reaction of hydraziae and sulfonyl haUdes, generally the chloride RSO2CI. Some of these have commercial appHcations as blowiag agents. As is typical of hydrazides generally, these compounds react with nitrous acid to form azides (26), which decompose thermally to the very reactive, electron-deficient nitrenes (27). The chemistry of sulfonic acid hydrazides and their azides has been reviewed (87). 

Triethyl phosphite is an effective reagent for the deoxygenation of appropriate nitro (or nitroso) aromatic systems. Free nitrenes or some nitrenoid-like species may be involved, and the use of this reagent is illustrated by the examples below. It has the advantage over the azide approach in that two steps in the synthesis can be avoided. 

Important synthetic paths to azirines and aziridines involve bond reorganization, or internal addition, of vinylnitrenes. Indeed, the vinylnitrene-azirine equilibrium has been demonstrated in the case of trans-2-methyl-3-phenyl-l-azirine, which at 110 °C racemizes 2000 times faster than it rearranges to 2-methylindole (80CC1252). Created in the Neber rearrangement or by decomposition of vinyl azides, the nitrene can cyclize to the p -carbon to give azirines (Scheme 4 Section 5.04.4.1). 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

The third class of compounds to be discussed in this chapter are those in which an RE group (E = S, Se, Te) is attached to a nitrogen centre. This category includes amines of the type (REfsN and the related radicals [(RE)2N] , as well as organochalcogen(ir) azides, REN3, and nitrenes REN (E = S, Se). Covalent azides of the type RTe(N3)3 and R2Te(N3)2, in which the chalcogen is in the +4 oxidation state, have also been characterized. 

Acyl azides can undergo photolytic cleavage and rearrangement upon irradiation at room temperature or below. In that case acyl nitrenes 8 have been identified by trapping reactions and might be reactive intermediates in the photo Curtius rearrangement. However there is also evidence that the formation of isocyanates upon irradiation proceeds by a concerted reaction as in the case of the thermal procedure, and that the acyl nitrenes are formed by an alternative and competing pathway " ... 

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 concentration of alkyl azidoformate used in these decompositions is important since with an excess (0.5 molar equiv) of azide, thermolysis at 130°C results in the formation of 1 2 1 //-azepine (methoxycarbonyl)nitrene adducts as the major products.145,146... 

Photolysis of aryl azides in amine solution, with a tertiary amine as cosolvent to promote stabilization of the singlet nitrene, has met with some success. For example, the yield of 2-piperidino-3 W-azepme. obtained by the photolysis of phenyl azide in piperidine, is increased from 35 to 58% in the presence of A A /V. /V -tetramethylethylenediamine (TMLDA).180 Also, an improved yield (36 to 60 %) of A,(V-diethyl-3W-azepin-2-amine (38, R = Et) can be obtained by irradiating phenyl azide in triethylamine, rather than in dicthylaminc, solution.181 Photolysis (or thermolysis) of phenyl azide in TMEDA produces, in each case, 38 (R = Et) in 40% yield.181 In contrast, irradiation of phenyl azide in aniline with trimethylamine as cosolvent furnishes jV-phenyl-377-azepin-2-amine (32, R = Ph) in only low yield (2%).35... 

Thermolysis of the vinyl azide 26 in xylene yields ethyl 8-(mcthoxymcthyl)-l,8-dihydro-benz[2,3]azepino[4,5- >]indole-2-carboxylate (27) by attack of the vinyl nitrene at the 2-phenyl group.83... 

When unacylated azides are used as nitrene precursors, the first reaction with an alkene is a cydoaddition, generating the corresponding 1,2,3-triazoline, which often eliminates N2 under the fierce reaction conditions to give an aziridine product (Scheme 4.9 ). 

Since the mid-1990s, synthetic attention has been directed more towards the use of metal-stabilized nitrenes as synthetic effectors of alkene aziridination. In 1969 it was reported that Cu(i) salts were capable of mediating alkene aziridination when treated with tosyl azide, but the method was limited in scope and was not adopted as a general method for the synthesis of aziridines [12]. Metaloporphyrins [13] were shown to be catalysts for the aziridination of alkenes in the presence of the nitrene precursor N-tosyliminophenyliodinane [14] in the early 1980s, but the reaction did... 

Another conceptually unique approach in alkene aziridination has come from Johnston s labs. These workers shrewdly identified organic azides as nitrene equivalents when these compounds are in the amide anion/diazonium resonance form. Thus, when a range of azides were treated with triflic acid and methyl vinyl ketone at 0 °C, the corresponding aziridines were obtained, in synthetically useful yields. In the absence of the Bronsted acid catalyst, cycloaddition is observed, producing triazolines. The method may also be adapted, through the use of unsaturated imi-des as substrates, to give anti-aminooxazolidinones (Scheme 4.25) [32]. 

Organic azides and isocyanates as sources of nitrene species in organometallic chemistry. S. Cenini and G. La Monica, Inorg. Chim. Acta, 1976,18,279-293 (86). 

Analogous to the decomposition of diazoalkanes, thermolysis of azides leads to the production of nitrenes. This is exemplified for ethyl... 

The possible routes leading to azides 2 are outlined in Scheme 1. The only pathway which we can exclude the 2=>C=>D=>E=>2 sequence since neither intermediate E nor its possible derivative E could be detected in the reaction mixture. (P-Azido a,P-unsaturated ketones are known to afford isoxazoles via nitrenes derived by loss of nitrogen (refs. 4,10). Azides 2 may form either via intermediate A (Sn + E route) or via allyl bromide-type intermediate B (E -f Sn route), both routes may operate on the basis of experimental results obtained so far. 

Breakdown of Certain Double-Bond Compounds. The most common method of forming nitrenes is photolytic or thermal decomposition of azides," " ... 

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