Elimination of Nitrogen from Azides

The photoreactions of azides can in most cases be rationalized in terms of the formation of intermediate nitrenes which then undergo rearrangement, insertion, or addition. A theoretical study 

Photoelimination of nitrogen from fluoroalkyl azides gave the 

Studies of the photoreactions of aryl and heteroaryl azides have also been described. Nitro-substituted aryl azides 

Heteroaryl azides frequently undergo ring expansion on photoelimination of nitrogen fused azirine intermediates have been proposed. Irradiation of the 4-azidoisoquinolines (91), for 

Photoelimination of nitrogen is an efficient and mild method for the generation of nitrenes. Irradiation of the azide (106) results in formation of the -acylimine 

Tamura, S. Kato, Y. Yoshimura, T. Nishimura, and Y. Kita, Chem, and Pharm. Bull. (Japan), 1974, 22, 1291. 

The nucleophilic trapping of azirines with secondary amines is a well-documented approach to the study of the photochemistry of aryl azides. The major product of irradiation of phenyl azide (118) in the presence of di-n-butylamine is the 3i/-azepine (119). A flash photolytic study has shown that 

The addition of singlet nitrene derived photochemically from the azido-1,3,5-triazine (130) to nitriles (131) has been reported.77 The adducts (132) are further converted thermally into the triazine-diones (133). 

Interest in the photochemical generation and fate of acyl nitrenes has again been expressed. In benzoyl, p-methoxybenzoyl, and m-fluorobenzoyl azides, Curtius rearrangement of the photochemically generated acyl nitrenes to the corresponding isocyanates competes with formation of insertion products in halogen-free solvents.78 In halogenomethanes, the yields of isocyanates are 

Photodecomposition of carbohydrate-derived geminal diazides appears to proceed via intermediate carbenes, ° whereas irradiation of the diazidomethylpyrimidine (70) in acetone affords the uracil carboxylate (71), but only in the presence of oxygen. 

A ketene intermediate (72) has been proposed in the photo-chemically induced conversion of lO-azido-lO-demethoxycolchicine (73) into the nitrile (74).  

Further studies of the photochemistry of aryl azides have been reported. The photodecomposition of phenyl azide has been studied in an argon matrix at 12K the ring expanded product, didehydro- 

A key step in a new stereospecific approach to the tetrahydro-quinoline ring system present in virantmycin is the conversion of the azide (77) into the aziridine (78), a process which involves intramolecular photochemically generated nitrene addition.  

Studies of the photodecomposition of azido derivatives of PCB have attracted interest because of their potential use as photolabels in intracellular distribution studies.Polyfluorinated aryl azides are also of current interest as new reagents for photoaffinity labelling. The major products of photolysis of methyl 4-azidotetrafluorobenzoate in cyclohexane or diethylamine, for example, arise by insertion, a property which enhances its use in labelling. Singlet pentafluorophenyl nitrene, formed in an analogous fashion on irradiation of pentafluorophenyl azide, can be trapped by toluene as the insertion products (79) and (80). ° 

Further examples of the preparation of 2i/-azirines by irradiation of a,j5-unsaturated azides have been reported.The azirine (112) has been proposed as an intermediate in the photoreaction of 6-azido-l,3-dimethyluracil (113) with 

Ponomareva, A. M. Komagorov, and O. P. Studzinskii, Izv. Kvis/ . Uchebn. Zaved., Khim. Khim. Tekhnol., 1980, 23, 812. 

Isomura, S. Noguchi, M. Saruwatari, S. Hatano, and H. Taniguchi, Tetrahedron Lett., 1980, 21, 3879. 

Azidophenazine is converted, on irradiation in acetonitrile in the presence of amines, into 2-alkylamino-l-aminophenazines and 2-aminophenazine.  

Singlet nitrene, formed by direct irradiation of the pyrazole (125), undergoes cyclization in high yield to give the 5i/-pyrazolo[l,2-a]benzotriazol-4-ium inner salt (126). An alternative reaction pathway is preferred on triplet-sensitized 

The photodecomposition of aryl azides continues to attract most attention in this area although few additional details concerning the mechanism have been reported, particularly with reference to ring expansion via 1,2-didehydroazepines. Ring 

Particular attention has been devoted this year to the study of fluorinated aryl azides. This interest stems from their potential use as photoaffinity probes due to the ease with which perfluorophenyl nitrene undergoes C-H bond insertion. Perfluorin-ated azide derivatives of methyl benzoate afford photochemically 

I labelled photoaffinity probes. 24% Nitrene insertion into the N-H bond of diethylamine has, however, been observed on 

Heteroaryl azides undergo analogous photochemically induced ring expansion reactions. The 3-methoxy-4-azidopyrid-azines (87) were converted in this way via the unstable lH-1,2,5-triazepines (88) into the 4H-1,2,5-triazepines (89) on irradiation 

An unusually stable trialkyltriaziridine (85) has been prepared by irradiation of the azide (86) in acetonitrile. Vinyl azides are converted by photoelimination of nitrogen into 2H- 

Recent experiments have established with a fair degree of certainty that 1,2-dehydroazepines are intermediates in the photodecomposition of aryl azides. The dehydroazepine (91), for example, has been detected at room temperature by time-resolved 

Competing singlet- and triplet-derived cyclizations have been 

The photoreactions of heteroaryl azides have also been examined in detail. Loss of nitrogen followed by ring expansion 

Efficient intramolecular nitrene insertion reactions have 

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The most reliable method for generating nitrenes is the thermal or photochemical elimination of nitrogen from azides. An alternative method which is useful for indole and carbazole synthesis is the deoxygenation of aromatic nitro compounds with trivalent phosphorus compounds. Triethyl phosphite is the most commonly used reagent, though more reactive compounds may be useful in special cases (B-79MI30600). 

Elimination of Nitrogen from Azides and Related Compounds... 

The reaction of 1-methyl-1,2,3,4-tetrahydropyridine 62 and azides 50a-c in dry ether at 25°C afforded the l-methylpiperidylidene-2-sulfon(cyan)amides 65a-c in good yield (82JHC1259). The reaction proceeds via a triazoline intermediate 63, which loses nitrogen to afford 65. The elimination of nitrogen from triazoline intermediate 63 occurs by two possible mechanisms [68JCS(C)277]. In path A, the 63 could eliminate nitrogen to give first an unstable 2,7-diazabicyclo[4.1.0]heptane... 

Finally, elimination of nitrogen from phosphinous azides leads to the formation of cy clophosphazenes ... 

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]. 

The use of reductive alkylation conditions has been employed to access tricycles from the azide 353 <2002S242> (Equation 95). Hydroboration of the alkene double bond with dicyclohexylborane followed by reaction with the azide and subsequent elimination of nitrogen and cyclization gave the linear tricyclic diketopiperazine 354 and 355 as a mixture of diastereoisomers. 

Acyl azides 268, derived from furan, thiophene and selenophene, add slowly at room temperature to the strained double bond of 5-methylenebicyclo[2.2.1]hept-2-ene. Two regioisomeric triazolines, 269 and 270, which form in the first step, are unstable and decompose with elimination of nitrogen to provide aziridine derivatives 271. Products 271 are isolated in good yield (73-85%). It is worthy to note that not only the terminal, unstrained double bond in the starting material, 5-methylenebicyclo[2.2.1]hept-2-ene, is unaffected, but also the typical dipolarophiles like esters of crotonic, propiolic and byt-2-ynoic acids do not react with azides 268 under these conditions (Scheme 39) <2002J(P1)1420>. 

These reactions are important in synthetic organic chemistry, because they lead to highly reactive chemical species called carbenes and nitrenes. A carbene has two unpaired electrons on a carbon atom, a nitrene has two unpaired electrons on a nitrogen atom. They are formed through the elimination of N2 from azo-compounds, RN2, and from azides, RN3 (Figure 4.34b). 

Derivatives of triazole have been obtained by Fusco et al,280 from phenyl azide and 1-morpholinocyclohexene. Their decomposition leads to cyclopentanecarboxylic acid by elimination of nitrogen and ring contraction.281 The dienamine obtained from piperidine and... 

Metal nitrene complexes were used in a number of C-H amination reactions (recent reviews [358, 359]). Copper ketiminate complexes react with azides to nitrene complexes, which were isolated [360]. (p-Ketiminate)copper(I) complex 262 (2.5 mol%) serves therefore as an efficient catalyst for the intermolecular C-H amination of alkylarenes, cycloalkanes, or benzaldehydes 260 using adamantyl azide 261 as the nitrogen source ig. 68) [361]. The corresponding adamantyl amines or amides 263 were isolated in 80-93% yield. Copper complex 262 forms initially a dinuclear bridged complex with 261. From this a copper nitrene complex is generated by elimination of nitrogen, which mediates the hydrogen abstraction from 260. 

The nitrogen source for the aziridination of alkenes, a nitrene or nitrenoid, can be generated in various ways (1) oxidation of a primary amine (2) base-induced -elimination of HX from an amine or amide with an electronegative atom X (X = halogen, O) attached to the NH group or by -elimination of metal halides from metal A-arenesulfonyl-A-haloamides (3) metal-catalyzed reaction of [A-(alkane/arenesulfonyl)imino]aryliodanes (4) thermolytic or photolytic decomposition of organyl azides and (5) thermally induced cycloreversion reactions . 

With the exception of the above report, there exists very little evidence for the intermediacy of discrete nitrene intermediates in alkyl azide thermolyses. A unimolecular process may arise either from a rearrangement concerted with elimination of nitrogen, or from a ratedetermining elimination of nitrogen followed by a fast rearrangement (equation 48). Several tertiary aliphatic azides were synthesized to determine whether processes other than rearrangement could be... 

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