1.2.4- Triazole 4-imines, synthesis

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

More recently, Williams has described the one pot synthesis of 2-substituted oxazoles 11 by the thermolysis of triazole amides 9 the reaction does not proceed photo-chemically.<92TL1033> Although the reaction does not involve addition to a nitrile, it is an interesting application of a diazo compound since the proposed zwitterionic intermediate 10 is a resonance form of a diazo imine, so formally the reaction may be thought of as a thermal decomposition of a diazo imine (Scheme 6). 

The meso-ionic l,2,4-triazol-3-imines can in principle exist as isomers 216 and 217, but only recendy has a specific synthesis of these two isomers been described.143 Aryl isocyanide dichlorides (218)144 and... 

Although several early reviews provide brief discussions on olefin-azide additions,6-9 the greater part of the work on imine-diazoalkane reactions is more recent and not covered previously.10,11 The major methods of triazoline synthesis are outlined in a recent treatise on 1,2,3-triazoles.13... 

On the basis of the same principle, we developed a three-component synthesis of macrocycles starting from azido amide (46), aldehyde (47) and a-isocyanoaceta-mide (48) (the cx-isocyanoacetamides are easily available, see [84—86]) bearing a terminal triple bond (Scheme 11) [87]. The sequence is initiated by a nucleophilic addition of isonitrile carbon to the in situ generated imine 50 led to the nitrilium intermediate 51, which was in turn trapped by the amide oxygen to afford oxazole 52 (selected examples [88-94]). The oxazole 52, although isolable, was in situ converted to macrocycle 51 by an intramolecular [3+2] cycloaddition upon addition of Cul and diisopropylethylamine (DIPEA). In this MCR, the azido and alkyne functions were not directly involved in the three-component construction of oxazole, but reacted intramolecularly leading to macrocycle once the oxazole (52) was built up. The reaction created five chemical bonds with concurrent formation of one macrocycle, one oxazole and one triazole (Scheme 15). 

Other methods for the synthesis of l,4-dihydro-l,2,4,5-tetrazines 9 which can be explained by intermediate formation of nitrile imines 8 are the photolysis of 1,2,3-triazoles 2181 and sydnones 3,182 reaction of tetrazoles 4180 with tosyl chloride, elimination of pyridine from the pyridinium compounds 5,189-190 of hydrogen chloride from the hydrazonic acid chlorides 1 s.3-i88 or elimination 0f sulfinate from the a-sulfonyl hydrazone 7.189... 

Amino-1,2,4-triazoles (50) or their derivatives are usually starting material for the synthesis. They are readily available and already contain the exocyclic N-N bond required for heteroaromatic A-imines. 4-Amino-1,2,4-triazoles can be quaternized by alkyl halides or tosylates at the N-l atom to give the salt 52.79-82 (Scheme 5) The orientation of quatemization is proved by the reactions in Scheme 6 for the example of the quaternary acylamino salts 52. Quaternary salts of the type 52 can also be prepared by reaction of 1,3,4-oxadiazolium salts (51)83 with aryl hydrazines84 and from aryl hydrazine hydrohalides and orthoesters.86 With alkali, the 1-alkyl-s-triazole-4-imines8(7-82 86 can be obtained in the normal manner from these salts (Scheme 5). The free A-imines are all stable except the A-unsubstituted compound itself.87 Recently, other structures were tentatively reported 88 for the deprotonation products of analogous quaternary salts (52) with hydrazine. 

Iminoyl chloride 17 reacted with tetrazoles 18 analogously to afford the 1,2,4-triazoles 19 in excellent yield. The electrocyclizaton of A -imino nitrile imines of the type 20 provided the key step for this general synthesis of 1,2,4-triazoles. Cyanuric chloride, as a triple aromatic imidoyl chloride, was treated with three equivalents of 5-phenyltetrazole to give 21 in 79% yield. ... 

A rhodium synthesis of sulfenylated imines containing a quaternary centre has been reported through a denitrogenative [2,3]-sigmatropic rearrangement of 4-aryl-, 4-alkenyl-, and 4-alkyl-A-sulfonyl-l,2,3-triazoles with aryl (alkyl)allyl sulfides (Scheme 57)7 ... 

Boyer, A. Rhodium(lI)-catalyzed stereocontroUed synthesis of dihydrofuran-3-imines from l-Tosyl-l,2,3-triazoles. Org. Lett. 2014, 16, 1660-1663. 

Sosnovskikh VY, Usachev BI (2002) A convenient synthesis of 4(5)-(2-hydroxyaroyl)-5(4)-tiifluoromethyl-l,2,3-triazoles from 2-trifluoromethylchromones and chromen-4-imines. Mendeleev Commun 12 75-76... 

The synthesis of meso-ionic 1,3,4-thiadiazole-imines described by Grashey et al. (see Vol. 3, p. 698) has been independently described by a Russian group of workers. The conversion of meso-ionic 4,5-diphenyl-l,3,4-thiadiazole-2-thiones into meso-ionic l,2,4-triazole-3-thiones under the influence of amines has also been further exemplified. ... 

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