1.2.4- Triazolines, formation

It has not yet been determined which structure [3] or [3 ] the triazoline has. The reaction mechanism of triazoline formation proposed by P.Scheiner, suggests that the structure may be 5-isopropyl-l-phenyl-A -i,3-triazoline(structure[3]). This conclusion was also supported by the fact that 3-methy 1-2-butylidene-aniline[5] was obtained by the decomposition of the triazoline (vide infra). 

Lithium aluminum hydride has been used to convert the triazol-5-ones 343 to both triazoles (345) and triazolines (346). The yields of the former are low (15-30%) by this method, triazoline formation being preferred. ... 

The full synthetic potential of nitrile ylides in 1,2,4-triazoline synthesis has not yet been explored the few available studies are confined to reactions with symmetrical dipolarophiles. Substituent effects of unsymmetri-cal dipolarophiles on the regiochemistry of triazoline formation are not known. 

Addition of a discrete arylnitrene to an alkene was first reported in 1971 although addition of ethoxycarbonylnitrene to olefins was well documented. Photolysis (or thermolysis) of ferrocenyl azide " (25) in cyclohexene yields the aziridine 26 and the predictable products 27-29. The possibility of triazoline formation prior to nitrogen elimination or concerted addition and elimination from the azide were considered to be very unlikely ... 

Azides can use enamines as dipolarophiles for ],3 cycloadditions to form triazolines. These azides can be formate ester azides (186), phenyl azides (187-195), arylsulfony] azides (191-193,196), or benzoylazides (197,198). For example, the reaction between phenyl azide (138) and the piperidine enamine of propionaldehyde (139) gives 1 -phenyl-4-methy l-5-( 1 -piperidino)-4,5-dihydro-l,2,3-triazole (140), exclusively, in a 53% yield (190). None of the isomeric l-phenyl-5-methyl product was formed. This indicates that the... 

The overall pathway for the conversion of the unsaturated azido ether 281 to 2,5-dihydrooxazoles 282 involves first formation of the dipolar cycloaddition product 287, which thermolyzes to oxazoline 282 or is converted by silica gel to oxazolinoaziridine 288. While thermolysis or acid-catalyzed decomposition of triazolines to a mixture of imine and aziridine is well-documented [71,73], this chemoselective decomposition, depending on whether thermolysis or exposure to silica gel is used, is unprecedented. It is postulated that acidic surface sites on silica catalyze the triazoline decomposition via an intermediate resembling 289, which prefers to close to an aziridine 288. On the other hand, thermolysis of 287 may proceed via 290 (or the corresponding diradical) in which hydrogen migration is favored over ring closure. 

Berlin, K. D., and L. A. Wilson Reaction of Phosphoryl Azides with Norbornene. Formation of a Novel Phosphorylated Triazoline. Chem. Comm. 1965, 280. 

The nonsymmetrical quinolizidine 373 was obtained from the acyclic symmetrical precursor 372 by means of a reaction sequence comprising azide formation, intramolecular 1,3-dipolar cycloaddition, thermal triazoline fragmentation to a diazoalkane, and Michael addition individual steps, as shown in Scheme 85 <2005CC4661>. 

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. 

An intramolecular version of an azide cycloaddition of 221 and 222 provided cyclopropylimines 224 and 225 via formation of triazoline 223 followed by extrusion of nitrogen with concomitant 1,2-hydrogen shift (Scheme 36) [58], The cyclization was found to be solvent dependent polar solvents such as DMF gave the best yields, whereas benzene gave several side products. 

Photoelimination of nitrogen from 1,2,3-triazolines has been widely used as a synthetic route to aziridines the reaction has been reviewed.355 Recent applications include the formation of a new valence isomer (425) of azepine from the triazoline 426,356 and conversion of the triazoline 427 into the aziridine 428, a process with potential as a synthetic route to mitomycins.357... 

Fluoroalkanesulfonyl azides 281 add readily to vinyl ethers to provide triazolines 282 in good yield (67-84%). At room temperature, slow decomposition of the products is observed with evolution of nitrogen and formation of piperazine derivatives 284. No other products are observed. Formation of piperazines 284 must involve cleavage of the triazoline ring with formation of zwitterionic intermediates 283 (Scheme 42) <2004JFC(125)445>. 

Formation of triazoline by addition of phenylazide to 3-methyl-l-butene and its photodecomposition products... 

In common with other azodicarboxylic acid derivatives, the uses of 4-phenyl-l,2,4-triazoline-3,5-dione are many. It undergoes a Diels-Alder reaction with most dienes11-14 and is, in fact, the most reactive dienophile so far reported.15 16 As with the formation of all Diels-Alder adducts the reaction is reversible, and in the case of the adduct with 3-j3-acetoxy-17-cyano-5,14,16-androstatriene, the reverse reaction can be made to proceed under especially mild conditions.14 An instance has also been reported of the dione photochemically catalyzing other retro Diels-Alder reactions.17 Along with the proven use of azodicarboxylic ester,18-18 the dione should be potentially important in the preparation of strained ring compounds. 

The mechanism of the acid-catalyzed decomposition of 1-alkyltriazolines has been studied <93JOC2097>. The hydrolytic decomposition of these triazolines in aqueous buffers leads predominantly to 1-alkylaziridines with lesser amounts of 2-(alkylamino)ethanol, alkylamines, and acetaldehyde. The rate of hydrolysis of 1-alkyltriazolines is about twice as fast as that of the analogous acyclic 1,3,3-trialkyltriazenes and varies in the order t-butyl > isopropyl > ethyl > butyl > methyl > propyl > benzyl <92JOC6448>. The proposed mechanism, involving rate-limiting formation of a 2-(alkylamino)ethyldiazonium ion, is shown in Scheme 65. A theoretical study ab initio calculation) of the acid-induced decomposition of 4,5-dihydro-l,2,3-triazolines has also been reported <91JA7893>. 

A -Triazolines (350) are easily converted into the corresponding 8-azapurines (351) on treatment with ethyl formate and sodium ethoxide (Equation (31)) <88S879>. When 5-amido-A -l,2,3-triazoline (352) is treated with trifluoroacetic acid, the 2-methyl-1,2,3-triazole (353) is afforded (Scheme 67) <91JCS(P1)3361>. 

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. 

Reports of pericyclic cyloadditions to other azepine systems are rare. Addition to the diene system of 6,7-dihydro-l//-azepines occurs readily with DMAD (72CPB1740) and with N-phenylmaleimide (73JA7320). The 5,5a-dihydro-3-benzazepin-2-one (157), a suspected but non-isolable intermediate in the formation of l,2,4,5-tetrahydro-3//-3-benzazepine-2,4-diones by photoaddition of diphenylketen to amino-2//-azirines, has been trapped in the photolysate by N-phenyl-1,3,4-triazoline-2,4-dione as the [4+2]tt adduct (158). Its structure was confirmed by X-ray analysis (80JOC2951). 

Benati et al. (17) reported intermolecular cycloadditions of aryl azides with 1,4-naphthoquinone (72) at ambient temperature. The triazoline intermediate 73 was unstable even at room temperature, leading to the formation of a mixture of products 74-77 (Scheme 9.17). 

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