Triazoline Derivatives

Triazoline Derivatives. Several vinyl- or cyclopropyl-triazenes have been found to exist in the A -triazoline form, e.g. (347) (348) or (349) (350).  

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The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

A competing reaction is thermal elimination of nitrogen from the triazolines. Some triazolines derived from eyclic enol ethers and enamines failed to give triazoles for this reason. In general, however, yields are very good. 

The addition reactions of aryl azides onto enamines bearing a carbonyl, sulfonyl, or nitro group in the 0 position with respect to the nitrogen atom have been investigated by Italian authors.240-241 The expected triazoline derivatives could not be isolated but were immediately converted into the corresponding 1,2,3-triazoles (49) and secondary amines. The reaction of p-nitrophenyl azide with l-benzoyl-2-morpholino-l-propene (48) is given as a typical example. 

The tiYins-triazolines in Scheme 61 (R1 = CH3) epimerize to cis-trans mixtures similar to triazolines derived from simple enamines (Section II,A,3,a). This results from triazoline cycloreversion250 and the isomerization of the enamino compounds thus formed.135,250... 

Aromatization of Triazolines Derived from Active Methylene Compounds... 

Fused-ring triazolines derived from 3,3-dimethylcyclopropene dicarboxyl-ate,442 Dewar thiophene (as was shown in Scheme 20)161 and cyclobutadiene undergo thermal isomerization to diazoimino compounds in a retro-1,3-cycloaddition (Scheme 146). 

Numerous aziridines have been prepared by triazoline photolysis it is the principal route to the synthesis of N-arylaziridines. Photolysis of triazolines derived from simple79,113,144 and cyclic79,87,113 olefins as well as norbomene... 

The primary adducts from the reaction of tetrachlorocyclopropene and azides yield chlorinated azabutadienes.170b The triazoline derived from Dewar benzene and phenyl azide, when heated in the presence of aluminum chloride, yields unique ring-enlarged heterocycles (Scheme 168).484... 

Second, intramolecular cyclization involving the azido group and the double bond could yield 1,2,3-triazoline derivatives these may be thermally unstable and may undergo nitrogen elimination to afford azirine derivatives. The reaction of perfluoro-2-methylpent-2-ene with NaN3 in a 1 2 acetonitrile-ethanol mixture at — 10°C (2 h) yielded stable 5-ethoxy-5-pentafhioroethyl-4,4-bis(trifluoromethyl)-4,5-dihydro-1H-1,2,3-triazole 9, whose structure was confirmed by X-ray analysis, Fig. 1 (01 JFC(110)21, 97ZOR772). 

By contrast, 1,2,4-triazole carbene 354 displays electrophilic character. Thus, it reacts with alcohols and amines producing triazoline derivatives 355 in quantitative yields. Oxygen or sulfur gives triazolinone and triazolinethione derivatives 356 (similar reaction with tellurium is known for imidazol-2-ylidenes). Reactions of 354 with dimethyl maleate or dimethyl fumarate lead to compounds 357, probably via ring opening of a cyclopropane intermediate with subsequent 1,2-hydrogen shift. 

Altememi GF, Arif IS, Alghrary NF, Muhieldeen Z. Investigation of the pharmacological activity of two acetylenic triazoline derivatives. ProgrNeuro Psychopharma-col Biol Psychiatr 1995 19 263-72. 

Azides are very versatile and valuable synthetic intermediates, known for their wide variety of applications, and have been employed for the synthesis of a number of important heterocyclic compounds. Azides also represent a prominent class of 1,3-dipoles, and their cycloaddition to multiple tt-bonds is an old and widely used reaction (1988CR297). The dipolar cycloaddition of an azide to an alkene furnishes a triazoline derivative (2003MI623). Azide-alkene cycloadducts can extrude nitrogen at elevated temperatures to form aziridines or imines, depending upon the substrate and reaction conditions. The cycloaddition of azides with alkynes affords triazolidine derivatives which have been a focus in the area of chemical biology and have received much recent attention (2008AGE2596, 2008CR2952). In this section of our review, we recount some developments of the 1,3-dipolar cycloaddition reaction of azides that have been used for the synthesis of various alkaloids. 

Figure 18 Examples of adducts of triazoline derivatives used for the measurement of vitamig analogs and metabolites. (From Ref. 7.)...

Benzyl azide 39 (R = Ph-CH2-) reacts with dimethyl fumarate to form a triazoline derivative Similarly, carbamyl azide 39 (R = NH2-CO-)... 

Earlier, we observed that diazomethane reacts with MA at 20 C to yield a ring-enlarged lactone 27 due to carbene insertion into the OC—O bond of the anhydride. It has been observed that trimethylsilyl azide (TMSA) instead inserts into the bond between the olefinic carbon and carbonyl grouping. No triazoline derivative was reported. Washburne et utilized this reaction to synthesize oxauracils. They treated MA with TMSA to obtain the silyl derivative 41 which could be converted to oxauracil 42 in a 60-80% overall... 

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