Diazo compounds 1.2.3- triazolines

The toluene- )-8ulfonamido anion may be lost from this, giving the diazo compound directly, or ring closure (which may be reversible) can take place, giving the triazoline anion (2). 

The [3 + 2] cycloaddition of diazo compounds to imines or nitriles is an alternative approach to the preparation of 1,2,3-triazoles and 1,2,3-triazolines. For reviews, see CHEC-I <84CHEC-I(5)7I7>. 

Carrie and co-workers studied the cycloaddition of oxime esters derived from methyl cyanoacetate and malonate esters 82 (Scheme 8.20) with diazomethane and some monosubstituted derivatives. Thermally labile 1,2,3-triazolines 83 were obtained when tosyloxy- and benzoyloxyimines were used (141), while methyl acetoxyimino-cyanoacetate (82, X = CN, Y = C02Me, = Ac) gave products derived from both a 1,2,3- and a 1,2,4-triazoline, depending on the stmcture of the diazo compound (142). Not unexpectedly, diazomethane reacted with the corresponding imino-malononitrile (82, X = Y = CN) system at the nitrile function rather than at the C=N bond (143). 

The triazoline resulting from the addition of ethyl azidoformate to phenylketene dimethylacetal at — 15°C for two months has been shown to exist in equilibrium with the isomeric diazo compound (Scheme 68).272,273... 

The diazoacetonitrile-imine reaction may be considered complimentary to azide addition to cinnamonitriles because in the latter case only triazoline thermolysis products result.284 The reversed order of reactivity of the diazoacetonitrile to that of diazomethane implies an electrophilic attack on the imine and is explained in terms of a LUMOdi MC lonit[ile-HOMOin,int controlled interaction. Thus electron-rich enamines, which do not react with diazoalkanes, may be expected to react with electron-poor diazo compounds. 

Triazolines resulting from the addition of diazoalkanes to ketenimines and carbodiimides generally isomerize spontaneously to triazoles (see Scheme 104).367-371 Similarly, diazo compounds with carbodiimides also lead to triazoles (Scheme 16)368 369-371 the migratory aptitude of substituent groups R1 and R2 is of the order, Me3Sn > Me3Si > H.368... 

However, the possibility of equilibrium between triazoline 4-carboxylic esters and the ring-opened diazo compounds (Section II,A,4,a) poses a problem as to which entity is actually oxidized. In fact, the open-chain tautomers formed from the addition of phenyl azide to acrylic and cinnamic esters are oxidized in good yield to the triazoles by permanganate (Scheme 119).32-28" 398 When the diazo compound is formed with ease, the oxidation is very smooth284 thus the diazo compound from the addition of phenyl or methyl azide to benzylideneacetone is oxidized rapidly in air to a triazole-4-carboxylic ester.284 A similar mechanism may be proposed to... 

The triazoline diazo compound equilibrium may be considered to play a role in the cis-trans isomerization332 and oxidation (Scheme 119)284 of certain triazolines. Triazole formation by elimination of amine214 or alcohol405 is also postulated to involve intermediate diazo compounds (Scheme 123). Unlike normal triazolines, the inability of 1-fluorotriazolines to undergo thermolysis or photolysis reactions to yield aziridines is ascribed to the fact that the triazoline always exists in equilibrium with the diazo compound (Scheme 98).356 Spontaneous isomerizations of triazolines not... 

The reaction of dienamines and sulfonyl azides provides a method for the synthesis of vinyldiazomethanes.233,431 Likewise, the pyrolysis of a fluo-rinated 1-benzyltriazoline over a nickel surface yields difluorodiazometh-ane.145 The formation of diazo compounds from the reaction of azides with alkylidene phosphoranes apparently originates from an intermediate triazoline compound (Scheme 145)408,411 412,415,441... 

Spontaneous isomerization of triazolines to diazo compounds can lead to addition of the latter to a second molecule of olefin, especially in the case of acrylic derivatives, resulting in a A pyrazoline, which by proto tropic rearrangement, gives the A2-compound (Scheme 149). Pyrazolines have been observed in the reactions of alkyl,67 aryl,32,282 heterocyclic,283,453 and gly-cosyl288 azides. A A pyrazoline is reported from the addition of phenyl and tosyl azides to 3,3-dimethylcyclopropene in this case the diazoimine formed by a retro-1,3-addition of the primary cyclopropanotriazoline adduct reacts with another olefin molecule.82... 

Enamine formation occurs by the thermolysis of diazo compounds (Scheme 150)67 109,278 284 288,304 332 453 454 via a carbene-like intermediate.284 332 When R1 = Ph, it enters into competition with hydrogen migration,284,332 and the electrophilic character of the carbene enhances the migration of the dimethylaminophenyl more than the phenyl.332 When triazoline synthesis is carried out at temperatures higher than that at which thermolysis of diazo compounds occurs, enamines are obtained exclusively, as in the addition of phenyl azide to cinnamic nitriles and ketones, with phenyl migration dominating in the nitrile.284 Enamine is also formed quantitatively in the reaction of ethyl diazoacetate with benzylideneaniline at 110°C.455... 

Triazoline thermolysis leads to aziridines, diazo compounds, imines, or enamines a diazonium betaine is postulated as the intermediate that can undergo stabilization by different pathways,16,30,806,112,465 as depicted in Scheme 161. Imine and enamine formation may occur directly from the diazonium betaine806,112,226 237 247 or via the diazo compound.32 Acceleration of the rate of thermolysis of 4,5-dialkyl-substituted triazolines in polar solvents is commensurate with the betaine intermediate,100,112,457,466 and attempts to prove a 1,3-zwitterionic intermediate have failed 467-469... 

The decomposition of the diazo compounds (207) is 45 times slower than that of the corresponding 1,2,3-triazoline (205). The exclusive generation of the enamino ester (209)... 

The cleavage of the triazolines formed by the addition of azides to oxo-enamines has already been mentioned in section II.B.3. This cleavage can be applied to the synthesis of diazo compounds unavailable otherwise. a-Diazobutyraldehyde (105) was obtained for the first time from a-ethyl- -dimethylaminoacraldehyde (104) and tosyl or picryl azide... 

DipoIar cycloadditions of fiiUerenes gave expected products. In cycloadditions with azides triazolines 25 were formed, while with diazo compounds such as 9-diazofluorene 22, spiro cyclopropane products 24 were directly prepared. In this case initially formed pyrazoline intermediate 23 was not isolated (Scheme 7.6) [13]. 

It is well known that alkyl azides also behave as 1,3-dipoles in intramolecular thermal cycloaddition reactions. The formation of two carbon-nitrogen bonds leads to triazolines, which are usually not stable. They decompose after the loss of nitrogen to aziridines, diazo compounds, and heterocyclic imines. There are a limited number of examples reported in which the triazoline was isolated [15]. The dipolar cycloaddition methodology has been extremely useful for the synthesis of many natural products with interesting biological activities [16], In recent years, the cycloaddition approach has allowed many successful syntheses of complex molecules which would be difficult to obtain by different routes. For instance, Cha and co-workers developed a general approach to functionalized indolizidine and pyrrolizidine alkaloids such as (-i-)-crotanecine [17] and (-)-slaframine [18]. The key step of the enantioselective synthesis of (-)-swainsonine (41), starting from 36, involves the construction of the bicyclic imine 38 by an intramolecular 1,3-dipolar cycloaddition of an azide derived from tosylate 36, as shown in Scheme 6 [ 19). 

The reaction of /7-nitrophenyl azide with the furanones 168,157, and 181a under the same reaction conditions was also studied (00H237). This dipolarophile reacted in a nonregiospecific manner with 5-methoxyfuranone 168 to give a mixture of the epimeric triazolines 261a and 261b. After flash chromatography, a diazo compound 262 and an enamine 263 were also isolated in poor yield (6 and 4%,... 

When active methylene compounds in basic medium react with tosyl azide, triazoles are never formed (Section IV,A,4), but the unstable triazoline intermediate undergoes a diazo transfer reaction in a Dimroth-type rearrangement.447 A typical example is the addition of tosyl azide to a 1,3-diketone... 

The triazolines formed from aryl azides and a,]8-unsaturated esters or ketones can be opened by bases to a-aminodiazo compounds. Methyl acrylate and phenyl azide thus yielded ethyl 2-diazo-3-phenylaminopropionate (106)... 

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