Triazolines rearrangement

The reaction of amines with the 4-phenylazo derivative (228) results in their rearrangement into triazolines. Depending on the basicity of the amines and the size of the alkoxy group, three different triazolines (229. 230, and 231) are obtained (Scheme 117) (454. 459, 472). In all cases, the first step involves nucleophilic addition of the amine to the carbonyl group followed by ring opening and further ring closure. 

The addition of acylazides leads to less stable triazolines, which lose nitrogen and rearrange to N-acylamidines (607). The triazolines obtained from sulfonylazides have been found to follow a similar reaction course as well as a path leading to the generation of diazoalkanes rather than nitrogen (596,599,608,609). 

Intramolecular dipolar azide-olefin cycloaddition of 723 took place upon heating in benzene to afford 724 (83JA3273). An alternative rearrangement process can take place upon photolysis of 724 to give 725. Mesylation of 4-(3-hydroxypropyl)-2,4,6-trimethyl-2,5-cyclohexadiene-l-one (78JA4618) and subsequent treatment with sodium azide in DMF afforded the respective azide 726 which underwent intramolecular cycloaddition to afford the triazoline 727 (83JOC2432). Irradiation of 727 gave the triazole derivative 728 (Scheme 126). 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

The reaction of ethyl azidoformate (93) with tetramethylallene yielded triazoline 94 and oxazoline 95 [88]. The triazoline 94 was formed by [3 + 2]-cycloaddition of azide 93 to the allene. The oxazoline 95 may result from [3 + 2]-cycloaddition of car-bethoxynitrene (96), which is formed from 93 by nitrogen evolution, to the allene or by the [2 +1] addition of the nitrene and subsequent rearrangement. 

The cycloaddition of picryl azide with phenoxyallene took place at the C1-C2 double bond of the allene exclusively to give the triazoline intermediate 97 [89]. This intermediate underwent a facile Claisen rearrangement to yield cyclohexadienone 98, which rapidly tautomerized to phenol 99. 

Additionally, uracil 6-iminophosphorane, isocyanate, and o-methyl-e-caprolactim ether join to form the intensely yellow pyrimido[4 5 4,5] pyrimido[6,l-n]azepine (360), as shown in Scheme 130. Upon ring closure, methanol is spontaneously eliminated. Diethyl azodicarboxylate affords with the other components pyrimido[4,5-e][l,2,4]triazoline (361), which is closely related to the alkaloid isofervenuline. The imidazo[5, -/][ ,2,4]tria-zine (362) results in a known Michael-type rearrangement sequence by treatment with diethyl acetylenedicarboxylate (86JOC149, 86JOC2787) in this latter case, the Michael-type addition occurs much faster than the expected three-component reaction [93H(35)1055]. 

Imines derived from ketones with an a-methylene group can react via their enamine tautomers, and mixtures of triazoles are also isolated from these systems. The triazoline adducts of the enamine tautomers are aromatized by treating with acid, and in these conditions the triazoline appears to undergo a Dimroth rearrangement before elimination of the amine, because two triazoles are obtained, one of which has... 

The (diphenylmethylene)aminocyclobutenecarboxylates 109 obtained by rearrangement of the DMPA-H adducts of 1-Me, 2-Me, contain a 2-azadiene unit and a cyclobutene moiety. Indeed, the parent compound 109 a reacted with 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD, [80]) at room temperature in a [4-1-2] cycloaddition mode to yield the tricyclic tetraazaundecene 132 in almost quantitative yield (Scheme 44) [8]. As substituted cyclobutenes, compounds 109 should be capable of opening up to the corresponding butadienes [1, 2b, 811. When compounds 109 were subjected to flash vacuum pyrolysis, the dihydro-isoquinolines 135 were obtained, presumably via the expected ring-opened intermediates 133, which subsequently underwent bn electrocyclization followed by a 1,5-shift, as is common for other 3-aza-l,3,5-hexatrienes [82]. 

Oximino cyanoacetate or malonate esters (Me02CC(CN)=N0Ts or (Me02C)2C= NOCOPh) reacted with diazoaUcanes (RCHN2) to give unstable 1,2,3-triazolines . Synthesis of Al-imidoylbenzotriazoles via benzotriazole-mediated Beckmann rearrangement of oximes is also described . ... 

The base-catalyzed rearrangement of oxadiazolylureas 184 into ben-zoylamino-l,2,4-triazolin-5-ones 185 has been mechanistically examined by using amines as catalysts in acetonitrile and benzene, and borate buffers at various pS in dioxan-water [90JCS(P2)1289]. For the piperidine-... 

In general, open structures II are energetically preferred over the closed forms I [8, 9], In the ring closed isomers I two unfavorable double bonds within five-membered rings would be required. No monoadduct with such a structure has been observed. Fulleroids such as 1-3 are usually formed via rearrangement of their pyrazoline-, triazoline- or ozonide [6,6]-precursor adducts accompanied by extrusion of N2 or O2 (see Chapter 4) [7,10-12]. 

Dipolar cycloaddition occurred preferentially at the electron-rich double bond of 22 to give the unstable triazoline 23, which on thermolysis led to extrusion of nitrogen and rearrangement to give the cyclopentenoid compound 25. The 1,3-dipolar cycloaddition-rearrangement sequence was subsequently extended to ultrasonic conditions. 

Junjappa and co-workers (9) reported the cycloaddition of sodium azide to the polarized ketene-(5,5)-acetal 33 to give the tiiazole 35 they also reported an intermolecular cycloaddition of tosyl azide 37 with the enamine 36 to give an unstable triazoline intermediate 38. Ring opening 38 followed by a Dimroth rearrangement afforded the triazole 41 (Scheme 9.9). 

De Kimpe and Boeykens (22) reported synthesis of the p-lactam derivatives 107 via cycloaddition of azides with 2-methyleneazetidines (104) (Scheme 9.22). Because of electronic control, the intermolecular cycloaddition of the azide with the enamine double bond resulted in the formation of the triazoline intermediate 105, ring opening and rearrangement of which gave the imino lactam 107. Although all attempts to convert compound 107 to the corresponding p-lactam 108 under acidic conditions were unsuccessful, under basic conditions compound 107 was converted into the p-amino amides 109. 

Sha et al. (45) reported an intramolecular cycloaddition of an alkyl azide with an enone in an approach to a cephalotaxine analogue (Scheme 9.45). Treatment of the bromide 205 with NaN3 in refluxing methanol enabled the isolation of compounds 213 and 214 in 24 and 63% yields, respectively. The azide intermediate 206 underwent 1,3-dipolar cycloaddition to produce the unstable triazoline 207. On thermolysis of 207 coupled with rearrangement and extrusion of nitrogen, compounds 213 and 214 were formed. The lactam 214 was subsequently converted to the tert-butoxycarbonyl (t-Boc)-protected sprrocyclic amine 215. The exocyclic double bond in compound 215 was cleaved by ozonolysis to give the spirocyclic ketone 216, which was used for the synthesis of the cephalotaxine analogue 217. 

An efficient stereoselective synthesis of the (pyrrolidin-2-ylidene)glycinate intermediate 325 was reported in a total synthesis of carzinophilin (326), employing an intramolecular cycloaddition of an azide with an alkene (63) (Scheme 9.63). The arabinose derivative 319 was converted into the required azide 321 via the triflate 320. Thermolysis of the azide 321 at 50 °C in THF produced the unstable triazoline 322, which on rearrangement gave the (pyrrolidin-2-ylidene)glycinate 325 in 60-72% overall yield from the triflate 320. 

The loss of CO, S, SO, S02 and N2 by thermolysis or photolysis has been used to make three- and four-membered rings for example, thiiranes (67) are obtained from (66) (CHEC 5.06.4.4). A2-1,2,3-Triazolines give aziridines and Wolff rearrangement of (68) gives (69). 

Enamines contain electron-rich double bonds and thus react readily with azides (in many cases at room temperature). Only one addition product is formed, namely a 5-amino-A2-triazoline, a result of electronic control.22 -223 Thus l-(p-nitrophenyl)-4-ethyl-5-morpholino-A2-triazoline (44) arises from the addition of p-nitrophenyl azide to 1-morpholino-l-butene (43). The addition products rearrange by heating into amidines (45).224... 

Cyanogen azide reacts with olefins at 0-35° to afford alkyl-idene cyanamides and/or N-cyanoaziridines arising from decomposition of an intermediate unstable triazoline. 54 With norbomadiene the isolated product is N-cyano-3-azatricyclo-[3.2.1.0s-4-M<,]oct-6-ene (58) which is unstable and rearranges into N-cyano-2-azabicycIo[3.2.1]octa-3,6-diene (59).167... 

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