Nitrenes isocyanates

Nitrenes, like carbenes, are immensely reactive and electrophilic, and the same Wolff-style migration takes place to give an isocyanate. The substituent R migrates from carbon to the electron-deficient nitrogen atom of the nitrene. Isocyanates are unstable to hydrolysis attack by water on the carbonyl group gives a carbamic acid which decomposes to an amine. 

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]. 

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 ... 

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). 

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 " ... 

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). 

Though we have presented this mechanism as taking place in three steps, and some reactions do take place in this way, in many cases two or all three steps are simultaneous. For instance, in the nitrene example above, as the R migrates, an electron pair from the nitrogen moves into the C—N bond to give a stable isocyanate ... 

N-benzylaniline with phosgene, and then with sodium azide to produce carbonyl azide 52. On heating, nitrogen is evolved and a separable mixture of nitrene insertion product 53 and the desired ketoindazole 54 results. The latter reaction appears to be a Curtius-type rearrangement to produce an N-isocyanate (54a), which then cyclizes. Alkylation of the enol of 54... 

A first terminal imido complex of nickel (121) was prepared according to Equation (3).468 The synthesis goes via the Ni11 amido compound (122) and uses the steric bulk of the arylimido group for stabilization. The Ni11 center in (121) is planar and three-coordinate. Reaction of (121) with CO or benzyl isocyanide leads to formal nitrene transfer with formation of (124) and (125), respectively. Further reaction with CO liberates the isocyanate and carbodiimide (Equation (4)). 69... 

Finally, a sulphonyl nitrene has been suggested as a possible intermediate in the reaction of benzenesulphonyl isocyanate with phenylmagnesi-um bromide at room temperature, to account for the formation of a 13% yield of vV-phenylbenzenesulphonamide 47>. 

This seems highly unlikely in view of the very mild reaction conditions. On the other hand, the photolysis of the isocyanate may yield the desired nitrene. 

In remembrance of the isolation of carbene 78 (Section m.C) it seems acceptable that 141, formed from 140 by a [l,2]-migration of the substituent, functions as a second intermediate. Carbene 141 can subsequently fragment into a nitrene 143 and carbon monoxide or open to an isocyanate 144, which alternatively may also be generated from an acid azide via acylnitrene 142. In comparison to calculated reaction pathways 75 78 and 82 81 (Schemes... 

Nitrenes can be generated from many precursors such as azides, isocyanates, ylides, heterocycles, and nitro compounds.236,237 Amongst these, azides are the most convenient precursors since they are easily prepared and can be decomposed by heat, light or a suitable catalyst. Despite considerable endeavors, no one has yet provided a synthetically viable method to use azides as sources of nitrenes.237 The breakthrough of nitrene chemistry was the recognization of the value of A-arenesulfonyl iminoiodinanes (ArS02N=IPh) as nitrene precursors by Breslow and Mansuy. - They reported inter- and intramolecular C-H insertions by tosylimino phenyl-iodinane (TsN=IPh) in the presence of Mn(m) or Fe(m) porphyrins or [Rh2(OAc)4]. Subsequently, Muller... 

FIGURE 7.10 Formation of the succinimido ester of IV-succinimidoxycarbonyl-P-alanine by reaction of three molecules of IV-hydroxysuccinimide (HONSu) with one molecule of dicy-clohexylcarbodiimide.25 The first molecule (N1) reacts to form the O-succinimido-isourea. The second molecule (N2) ruptures the ring by attack at the carbonyl, generating a nitrene that rearranges to the esterified carboxyalkyl isocyanate. The third molecule (N3) attacks the carbonyl of the latter. R3 = R4 = cyclohexyl SuN- = succinimido. 

Thermal or photochemical rearrangement of acyl azides into amines via isocyanate intermediates. While the thermal rearrangement is a concerted process, the photochemical rearrangement goes through a nitrene intermediate. 

In contrast to the somewhat limited synthetic utility of nitrenes, there is an important group of reactions in which migration occurs to electron-deficient nitrogen. One of the most useful of these reactions is the Curtius rearrangement 16 This reaction has the same relationship to acylnitrene intermediates that the Wolff rearrangement does to acylcar-benes. The initial product is an isocyanate, which can be isolated or trapped by a nucleophilic solvent. 

JV-Alkoxycarbonyl- and iV-arenesulfonyl-imines can be prepared by the reaction between pyridines and nitrenes, the latter being generated from the corresponding azides (72JOC2022, 64TL1733). Thermolysis of pyridinium iV-acylimines gives isocyanates and the parent heterocycle <79JCS(P1)446). 

Treatment of amides with bromine in alkaline medium promotes the Hofmann rearrangement, which may or may not involve a free nitrene intermediate." The oxidation of primary amides with lead tetraacetate and the resulting Lossen rearrangement also produces isocyanates, with the possible intervention of an acylni-... 

Two other observations are noteworthy. First, the yield of isocyanate (9) produced on photolysis of 7 in methylene chloride (an inert solvent) is 40%. Photolysis of 7 in cyclohexene leads to a 45% yield of aziridine adduct 10 and a 41% yield of isocyanate 9. Trapping the nitrene does not depress the yield of isocyanate Hence, isocyanate 9 and adduct 10 cannot be derived from the same reactive intermediate. Instead, the isocyanate must be formed from the excited state of the azide, that is, the excited azide (7 ) must partition between the formation of isocyanate and nitrene. 

Such a mechanism is also considered to operate in the photochemical reaction of Mo(jt-Cp)(CO)2(NO) with triphenylphosphine. Isolation of the isocyanate complex Mo(NCO)(jt-Cp)CO(PPh3)2 together with Mo(jt-Cp)(CO)NO(PPh3) results from trapping of the metal nitrene by carbon monoxide in an intramolecular process.122 Nitrene formation is also considered to participate in the process of conversion of Mo(NO)2(S2CNR2)2 to Mo(NO)(S2CNR2)3 using triphenylphosphine.119... 

The formation of isocyanates has also been observed in reactions outlined in equations (21)-(23). It has been shown that the reactions of equation (21) most probably proceed via coordination of the amine function followed by rearrangement with elimination of HX. The reaction with PPh3 is interesting because of the initial formation of a nitrene species via N—O bond cleavage. Formation of a nitrene intermediate as a crucial step in the formation of the NCO ligand has also been proposed for the reaction with diazomethane. 

Nonoxidative photocyclization also occurs in 2-diphenyl isocyanate (367) to form carbazole (368) and phenanthridone (369).390 The mechanism of this transformation is uncertain, and, in fact, little attention has been given to the photochemistry of isocyanates. Carbazole is also the principal product of nonsensitized photolysis of 2-azidobiphenyl391 the reaction presumably involves the cyclization of an intermediate nitrene. 

It was assumed that the rearrangement of N-anionic intermediate 181 into isocyanate 182 occurs as a synchronous process including the formation of a new C—N bond and the withdrawal of the anion acid (X ), but without formation of the intermediate nitrene. According to early papers, information about yields of naphthostyryl 174 (R = H), which is obtained from naphthaloimide 178 (R = H) by the Hofmann reaction, is contradictory. The procedure has been checked and developed preparatively by... 

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