1 - nitrene

The two-bond disconnection (re/ro-cycloaddition) approach also often works very well if the target molecule contains three-, four-, or five-membered rings (see section 1.13 and 2.5). The following tricyclic aziridine can be transformed by one step into a monocyclic amine (W. Nagata, 1968). In synthesis one would have to convert the amine into a nitrene, which-would add spontcaneously to a C—C double bond in the vicinity. 

Reductive carbonylation of nitro compounds is catalyzed by various Pd catalysts. Phenyl isocyanate (93) is produced by the PdCl2-catalyzed reductive carbonylation (deoxygenation) of nitrobenzene with CO, probably via nitrene formation. Extensive studies have been carried out to develop the phosgene-free commercial process for phenyl isocyanate production from nitroben-zene[76]. Effects of various additives such as phenanthroline have been stu-died[77-79]. The co-catalysts of montmorillonite-bipyridylpalladium acetate and Ru3(CO) 2 are used for the reductive carbonylation oLnitroarenes[80,81]. Extensive studies on the reaction in alcohol to form the A -phenylurethane 94 have also been carried out[82-87]. Reaction of nitrobenzene with CO in the presence of aniline affords diphenylurea (95)[88]. 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

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]. 

Fig. 5. Chemistry of cyclized mbbei—bis-a2ide negative acting resist, (a) Preparation of cyclized mbber resin from polyisoprene (b) photochemistry of aromatic bis-a2ide sensiti2ers. The primary photoproduct is a highly reactive nitrene which may combine with molecular oxygen to form oxygenated products, or may react with the resin matrix by addition or insertion to form polymer—polymer linkages.

The preparation and properties of these tertiary aminimides, as weU as suggested uses as adhesives (qv), antistatic agents (qv), photographic products, surface coatings, and pharmaceuticals, have been reviewed (76). Thermolysis of aminimides causes N—N bond mpture foUowed by a Curtius rearrangement of the transient nitrene (17) intermediate to the corresponding isocyanate ... 

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). 

Irradiation of ethyleneimine (341,342) with light of short wavelength ia the gas phase has been carried out direcdy and with sensitization (343—349). Photolysis products found were hydrogen, nitrogen, ethylene, ammonium, saturated hydrocarbons (methane, ethane, propane, / -butane), and the dimer of the ethyleneimino radical. The nature and the amount of the reaction products is highly dependent on the conditions used. For example, the photoproducts identified ia a fast flow photoreactor iacluded hydrocyanic acid and acetonitrile (345), ia addition to those found ia a steady state system. The reaction of hydrogen radicals with ethyleneimine results ia the formation of hydrocyanic acid ia addition to methane (350). Important processes ia the photolysis of ethyleneimine are nitrene extmsion and homolysis of the N—H bond, as suggested and simulated by ab initio SCF calculations (351). The occurrence of ethyleneimine as an iatermediate ia the photolytic formation of hydrocyanic acid from acetylene and ammonia ia the atmosphere of the planet Jupiter has been postulated (352), but is disputed (353). 

The porphyrin ligand can support oxidation states of iron other than II and III. [Fe(I)Por] complexes are obtained by electrochemical or chemical reduction of iron(II) or iron(III) porphyrins. The anionic complexes react with alkyl hahdes to afford alkyl—iron (III) porphyrin complexes. Iron(IV) porphyrins are formally present in the carbene, RR C—Fe(IV)Por p.-carbido, PorFe(IV)—Fe(IV)Por nitrene, RN—Fe(IV)Por and p.-nittido, PorFe(IV)... 

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). 

Fig. 6. Coupling of polymer chains via (a) photoinduced hydrogen abstraction free-radical reactions and (b) nitrene insertion/addition reactions.

Iminoboianes have been suggested as intermediates in the formation of compounds derived from the pyrolysis of azidoboranes (77). The intermediate is presumed to be a boryl-substituted nitrene, RR BN, which then rearranges to the amino iminoborane, neither of which has been isolated (78). Another approach to the synthesis of amino iminoboranes involves the dehydrohalogenation of mono- and bis(amino)halobotanes as shown in equation 21. Bulky alkah-metal amides, MNR, have been utilized successfully as the strong base,, in such a reaction scheme. Use of hthium-/i /f-butyl(ttimethylsilyl)amide yields an amine, DH, which is relatively volatile (76,79). 

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). 

Reactions with Radicals and Electron-deficient Species Reactions at Surfaces 4.02.1.8.1 Carbenes and nitrenes... 

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). 

The most important chemistry of azidoazoles is the fragmentation of derived nitrenes of which the prototypes are (453) (454) and (455) (456). Thus 5-azido-l,4-diphenyltriazole (457) evolves nitrogen at 50 °C (70JOC2215). 4-Azido-pyrazoles and -1,2,3-triazoles (458) undergo fragmentation with formation of unsaturated nitriles (8lAHC(28)23l). 

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)... 

Nitrenes have enjoyed appreciable application in the synthesis of a wide variety of heterocyclic systems, and the majority of the methods used for generating nitrenes have been utilized in these syntheses. 

The synthetic potential of nitrenes is more readily apparent in the synthesis of ring-fused systems (81AHC(28)309), which can be accomplished by cyclization onto a heteroatom or onto an adjacent ring, the latter having the possibility of reaction at carbon or at a heteroatom. 

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. 

Thermolysis of 4- and 5-azidopyrazoles has been studied by Smith (B-70MI40402, 81AHC(28)232). These compounds undergo fragmentation with formation of unsaturated nitriles via the nitrenes (474a) and (474b Scheme 42). 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

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). 

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