Nitrene intermediates

Preparation from Nitrene Intermediates. A convenient, small-scale method for the conversion of carboxyhc acid derivatives into isocyanates involves electron sextet rearrangements, such as the ones described by Hofmann and Curtius (12). For example, treatment of ben2amide [55-21-0] with halogens leads to an A/-haloamide (2) which, in the presence of base, forms a nitrene intermediate (3). The nitrene intermediate undergoes rapid rearrangement to yield an isocyanate. Ureas can also be formed in the process if water is present (18,19). 

A process for the commercial synthesis of -phenylene diisocyanate using terephthalamide [3010-82-0] as a precursor and involving N-halo intermediates has been studied extensively (21). The synthesis of 1,4-diisocyanatocyclohexane from terephthaUc acid [100-21-0] also involves a nitrene intermediate (22). 

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). 

Photochemical elimination of carbon dioxide from suitable precursors has given a variety of reactive intermediates at low temperatures where they are often stable and can be studied further. This approach has been utilized in attempts to generate new 1,3-dipolar species, and photolysis of (515) gave an azomethine nitrene intermediate (516) (see Section 4.03.6)... 

In the attempted thermolytic preparation of pyrroloisoxazole (32) from azidoisoxazole (31a), only cinnamoyl cyanide was isolated. The assumed intermediate nitrene (33) did not insert into the styryl bond, but rather ring rupture and loss of acetonitrile produced the product. Similar products were obtained from the homolog (31b) (Scheme 7) (79TL4685). The stabilized nitrene intermediate is similar to that postulated for diazofuryl- and diazoisoxazolyl-methanes (78JA7927, 79TL2961). 

The aforementioned mechanism is supported by the following experimental data. When oxime 13 was treated with Grignard reagent, 3% of the indole 15 was isolated, indicating the possible existence of nitrene intermediate 14. A 2-phenylazirine intermediate, on the other hand, has been isolated and characterized from the reaction under carefully controlled conditions (adding Grignard reagent to the oxime in toluene). ... 

The reactions of nitrenes are also similar to those of carbenes. As in that case, many reactions in which nitrene intermediates are suspected probably do not involve free nitrenes. It is often very difficult to obtain proof in any given case that a free nitrene is or is not an intermediate. 

Because reduction of 2-nitrodiphenyl with hexamethyldisilane 857 does not give any carbazole, nitrene intermediates can probably be excluded. The very polar 4-nitropyridine N-oxide 1003 can be reduced by 857 only in the polar solvent N,N-di-... 

Irradiation of 1-azidophosphetan-l-oxide (112) in methanol leads to the phosphonamide esters (113) and (114), although the stereochemistry of these products is not yet fully settled. Their formation is reasonably consistent with the intervention of a nitrene intermediate which inserts into the P—C and C—H bonds. 

A similar nitrene intermediate can also be postulated in the mechanism of nitrosobenzene hydrogenation. Indeed a standard way of producing Ph-N is from the reaction of Ph-NO with PPhs (17). In the hydrogenation of nitrosobenzene the principal product in the early stages is azoxybenzene [7, 18]. It was suggested that azoxybenzene was formed by the following sequence ... 

The triplet state is usually the ground state for non-conjugated structures, but either species can be involved in reactions. The most common method for generating nitrene intermediates, analogous to formation of carbenes from diazo compounds, is by thermolysis or photolysis of azides.246... 

Similar products are obtained from the photosensitized decomposition of the tertiary azides, suggesting that decomposition may result from the triplet azides under both direct and sensitized photolysis/461 Additional evidence for a discrete nitrene intermediate comes from the observation that this intermediate can be trapped by decomposition of the azides in the presence of good hydrogen donors such as tri- -butyItin hydride and jec-butyl mercaptan. Triarylamines result ... 

ESR spectra for a number of nitrene intermediates produced by photolysis at 77°K have been reported.<50) Analysis of these spectra has resulted in their assignment to triplet ground state nitrenes. 

Uncatalyzed thermal decomposition of sulphonyl azides is believed to give nitrene intermediates and nitrogen, in general ... 

Until recently, most of the evidence for the rate-determining formation of a nitrene intermediate came from experiments in which the nitrene was trapped or from the temperatures required to effect decomposition and the nature of the products formed. Horner and Christmann 5> observed that the rate of nitrogen evolution from /-toluenesulphonyl... 

The rate of decomposition of benzenesulphonyl azide to benzene-sulphonamide is said to be accelerated appreciably by thiophenol 18> in a radical-catalyzed process probably not involving a free nitrene intermediate. 

Photolysis of sulphonyl azides in dimethyl sulphoxide with 2537 A light gives IV-sulphonylsulphoximines 12 in 15—50% yield 5>. The reaction was formulated as going via a nitrene intermediate which was trapped by the nucleophilic solvent... 

In contrast to the reaction of benzamide and other carboxylic acid amides with lead tetraacetate, which has been said to proceed via an acyl nitrene intermediate 46>, methanesulphonamide and 2-biphenylsulphon-amide are completely inert towards this reagent 42>. 

Photolyzing with UV light may result in immediate reaction of the nitrene intermediate with a target molecule within Van der Waals distance, or may result in ring expansion to the nucleophile-reactive dehydroazepine. The ring-expanded product is reactive primarily with amine groups (Figure 5.31). 

Thermolysis of 5-amino-6-azido-1,3-dimethylxanthine 289 in chlorobenzene gave 3-aminoisofervenulin 290 possibly through a C-nitrene intermediate (92MI1). 

Thermolysis of 7-amino-6-azido-l,3-dimethylxanthine (386) in chlorobenzene gave 3-aminofervenulin (387) through a nitrene intermediate (92MI1). 7-Aminotheophylline 388 and 389 were oxidized by various oxidizing agents to give 309 and 311, respectively (89KGS95). 

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