Nitrenes reaction gives

Triazines have been formed from the reaction of imidazol-2-ylidenes with azides.68 The reaction could be thought of as the reaction of a carbene with a nitrene. The reaction gives 54-94% yields and one of the products was induced to lose nitrogen when heated to above 120 °C. 

The outcome of the nitrene addition reaction depends on the type of 7i-bond involved. In contrast to electron deficient olefins [26] and nonpolar olefins forming aziridines, electron rich olefins react with alkoxycarbonyl nitrenes to give oxazolines (Sch. 14) [22]. The same type of cycloaddition reaction leading to the production of five-membered rings has also been observed with nitriles [27] (such as compound 35 in Sch. 14) and isocyanates [28] as illustrated in Sch. 15. 

The triple bond of nitriles is attacked by aroyl nitrenes to give rise to oxadiazoles as illustrated in Sch. 25 [22,41]. However, additions of acyl nitrenes to olefmic double bonds can be carried out in acetonitrile solution because the cycloaddition reaction to the solvent is much slower. 

Overall, then, the Curtius rearrangement converts an acid chloride to an amine with loss of a car- tk>n atom—very useful. Also useful is the related Hofmann rearrangement, which turns an amide ito an amine with loss of a carbon atom. This time we start with a primary amide and make a trene by treatment with base and bromine. Notice how close this nitrene-forming reaction is to the tarbene-forming reactions we talked about on p. 1072. The nitrene rearranges just as in the Curtius reaction, giving an isocyanate that can be hydrolysed to the amine. 

In contrast to the nitrene reactions with aliphatic hydrocarbons, where only little amide formation occurs 25>69), in aromatic hydrocarbons much better yields of sulphonylamides are obtained 10.68,70), F0r example, thermolysis of benzenesulphonylazide and methanesulphonylazide in benzene gave 18% of benzenesulphonamide 16> and 14% ethanesulphonylamide, respectively 68). In contrast to the nitrene reactions in aliphatic hydrocarbons no coupling product such as biphenyl-derivatives was detected. This should have been the case however if abstraction of a single hydrogen atom did occur thus giving rise to an aryl radical as shown below. 

Sulphonyl azides react with strained olefins, at temperatures below those required for the formation of the corresponding nitrenes, to give aziridines and anils. These reactions have been reviev ed recently . Benzenesulphonyl azide reacts with norbomene in acetonitrile solution at 55-60° to give the aziridine (282) (64%) in 2—3 hr ° ° . It was found, however, that when benzene was the solvent, a quantitative yield of 282 was obtained at room temperature in about 1-5 hr ° . 

Carbonylnitrene intermediates have been postulated since 1891 , but a problem recurs for every reaction which can be formulated as a nitrene reaction one can always write a reasonable azide mechanism that leads to the same products. One such alternative is a two-step process in which the azide reacts with the substrate in a first step, to give an adduct or an intermediate radical or ion pair, which loses nitrogen in a second step. Another alternative is a concerted process, in which loss of nitrogen and product formation are simultaneous. An example of the former azide mechanism is the aziridine formation... 

From the effect of solvent (Table 15) it is evident that the reactions discussed are nitrene reactions hydrogen-rich solvents suppress ring contraction and give rise to solvent dimer (bibenzyl) and/or a yellow nitrene dimer. The structure of the dimer is not known, but one possibility is shown in 144. A similar (colorless) dimer was obtained from 9-phenanthridylnitrene at 500 ° 7). Xhe two dimers formed from 137 and 141 in cyclohexane have nearly identical IR spectra. How could a hydrogen-rich solvent promote dimeriztion There is evidence from aryl azide decomposition in solution that amino radicals are formed first, and these dimerize and dehydrogenate as shown for 1-naphthylnitrene in [Eq. (48)] 82). 

In the intermolecular reaction of the nitrene that is derived from tosyl azide with benzene, little of the A -tosylazepine (5) is obtained at normal pressures, but the yield is markedly increased when the reaction takes place under a high pressure of nitrogen for example, to 48% at ca 90 atm.In a similar reaction with dimethyl terephthalate, it is suggested that the reaction involves an initial [1,3] cycloaddition of the azide to the aromatic ring to give (6), rather than a nitrene reaction. 

Reaction of benzenesulphinyl azide with water proceeds via a nitrene to give overall oxidation of the sulphur moiety, to give the sulphonamide453, as shown in equation 111. 

Although aryl nitrenes often give poor yields of intermolecular C-H insertion products, the intramolecular reaction works well, and proceeds with retention... 

Nitrenes for the most part being electron deficient are highly electrophilic intermediates and therefore react with nucleophiles of all types. Tertiary amines, phosphines, sulfides, and sulfoxides all react with nitrenes to give ylides, in a reaction that is the reverse of their formation. In practice, dimethyl sulfoxide (DMSO) is often the most convenient nucleophilic trap since it can be used as the reaction solvent, and gives relatively stable sulfoximides (Scheme 6.40). Azo compounds, which are formally nitrene dimers, are common by-products in many nitrene reactions. However, the dimerization of two highly reactive species in solution is extremely unlikely on statistical grounds, and therefore the mechanism of azo compound formation probably involves the reaction of a nitrene, as an electrophile, with its precursor. 

It has been considered that a coordinated nitrene may give the same reaction and work in our group has shown that this is indeed possible in at least one case [260] (see also Chapter 5). However, it should be also noted that we now know that most reactions of nitro- and nitroso compounds with a metal complex occur through an intermediate electron transfer to the organic compound vide supra). Thus the formation of the radical anion of o-nitro- and/or o-nitrosobiphenyl should be considered as probable during the reaction. The reactivity of such radicals is virtually unknown and it cannot be excluded that these species, and not a nitrene intermediate, are responsible for the carbazole formation. The validity of carbazole formation as an indication for nitrene intermediates has been questioned very early [261]. It was shown that other reactions (including oxidation of 2-amino-biphenyl) can afford carbazole. Thus the results of this test should be taken with caution. 

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]. 

An early synthesis of pyrido[3,4-6]quinoxalines involved cyclization by strong heating of o-aminoanilinopyridinamine derivatives, e.g. (418) to give (419) (49JCS2540). In a related reaction, o-nitroanilinopyridines (420) were cyclized to pyrido-[2,3-6]- or -[3,4-6]-quinoxa-lines (421) by reduction with iron(II) oxalate, probably via a nitrene intermediate (74JCS(P1)1965). 

However, in some cases carboxylic acid-derived groups can participate in ring fission-reclosure reactions. Thus photolysis of 1,5-disubstituted tetrazole (399) gives nitrogen and appears to involve the amino-nitrene intermediate (400), which reacts further to give (401) (77AHC(21)323). 

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