1.2.4- Triazole ring closur

One of the most important biomolecules for which fluorescent sensing [94-96] is of great importance is nitric oxide [97-101]. Nitric oxide can react with several organic dyes, switching on their fluorescence as a result of a triazole ring closure reaction [94], There are also useful and selective NO optical sensors based on transition metal complexes (Figures 16.22 and 16.23) [94-96],... 

This method of ring closure is the most convenient for the synthesis of ring-fused 1,2,4-triazoles with this arrangement of nitrogen atoms. It has been used extensively to form the analogous [5,6] ring-fused systems, and structural ambiguity is only encountered... 

Oxidative procedures have been utilized for the synthesis of both monocyclic five-membered heterocycles and their ring-fused analogs, although the ease of synthesis of the precursors for the latter ring closures results in wider application of this procedure. A variety of oxidizing agents have been used and the conversion of the benzylidene hydrazidines (221) into the 4-arylamino-l,2,4-triazole (222) was effected with mercury(II) oxide (77BCJ953). 

Oxidation of the hydrazone of 2-hydrazinopyrazole (226) with Pb(OAc)4 in CH2CI2 is a two-step reaction. The azine (227) was formed as an intermediate and this underwent ring closure to the 3H-pyrazolo[5,l-c][l,2,4]triazole (228) (79TL1567). A similar reaction applied to the benzal derivative of 2-hydrazinobenzothiazole (229) gave 3-phenyl-[l,2,4]triazolo[3,4-6]benzothiazole (230) together with a by-product (231) (72JCS(P1)1519). 

Triazole-3(5)-thiol has been prepared by heating thio-semicarbazide and formic acid, by heating l-formyl-3-thiosemi-carbazide, and by heating 1,3,5-triazine and thiosemicarbazide. The ring closure of l-formyl-3-thiosemicarbazide using aqueous base was suggested by L. F. Audrieth and F. Hersman. 

Simple examples of diazoalkylideneamine-l,2,3-triazole equilibria have been demonstrated for a series of l,2,3-triazolo[l,5-a]pyrimidines by variable-temperature NMR [74JCS(CC)671]. Tautomers A, B, and C interconvert rapidly at elevated temperatures the energy barrier for these ring-opening-ring closure processes was found to be AG = 76 kJ mol (for = H, Me R = CONH2) (Scheme 111). 

As shown by Heindel and Corley (1979), ring closure also takes place if the nucleophilic nitrogen is part of a heterocycle, as in the diazotization of 5-amino-3-methyl-2-H-l,2,4-benzothiadiazine-l, 1-dioxide (6.50). In the tricyclic compound 6.51 formed initially, the thiadiazinedioxide ring is opened rapidly in water, forming 1-acetyl-7-aminosulfonyl-l-i/-benzo-l,2,3-triazole (6.52). 

The mesoionic tetrazole dehydrodithizone is transformed by iron penta-carbonyl into 4-phenyl-2-phenylazo-A2-l,3,4-thiadiazolin-5-one, presumably by a mechanism of ring opening, complexation, carbonyl insertion and subsequent ring closure (Scheme 128).193 Unfortunately, analogous processes do not occur on other mesoionic compounds in the 1,2,3-oxadiazole, s-triazole or tetrazole series, and the scope of this unusual carbonylation is probably limited. 

The synthesis of a series of thiazolo[2,3-c][l,2,4]triazole derivative 33 has been approached by base-mediated intramolecular cyclization of bromide 349 or acid-promoted ring closure of alcohol 350, obtained from pyrazinoyl-dithiocarbazate 348 (Scheme 33) <2004PS(179)2519>. 

In the ring closure of 5-amino-2,3-dihydro-17/-l,2,4-triazolo-3-thione 431 (R = NH2) with 1,2-dibromoethane in the presence of sodium methoxide (2equiv), compound 42 was formed as the main product (Scheme 50) <2003JHC821>. Similarly, the same type of functionalized thiazolo[3,2-A][l,2,4]triazoles 440 and 441 were isolated in the reaction of 1,2-dibromoethane with 2,3-dihydro-17/-l,2,4-triazolo-3-thione (431, R = H) or 2,3-dihydro-5-methyl-l/7-l,2,4-triazolo-3-thione (431, R = Me), using DMF as the solvent in the presence of potassium carbonate and benzyltriethylammonium chloride (CBTEA) (Scheme 50) <2004PS(179)1799>. 

Closure of the triazole ring can be achieved either by oxidative formation of the N-N bond, or condensation of an fV-aminopyridone. The latter was formed by iV-amination of pyridines with mesitylhydroxylamine (MSH), or by forming the pyridine ring, starting from cyanoacetic hydrazide with malononitrile or 2-cyanoacrylates. 

The same type of ring-closure reaction that leads to the [3,2- ]-fused 50 can also result, in principle, in formation of a [3,4- ]-fused ring system (see Sections 11.16.5.2 and 11.16.7). This case has been found when an amino group was present in the triazole ring, and formation of 51 has been supported by X-ray diffraction. The crystalline structure... 

Ring closure of the cyano group containing aniline (312) to 313 <1994T7019, 1996J(P1)225> followed the same pathway as that with the oxazine analogue discussed earlier with transformation of 291 into 292. Formation of the fused triazole 315 from 314 was also reported <1994FA245>. 

Scheme 47 contains syntheses of [l,2,4]triazolo[4,3- ]pyridazine derivatives by ring closure of the triazole moiety. Kozhevnikov et al. reported <2005MC31> an interesting ring transformation treatment of the... 

Matsuda et al. described the cyclization to a mesoionic derivative of the title ring system <1995H(41)329>. The starting compound of the ring-closure reaction is the anion 416, which was easily obtainable from ethyl [l,2,4]triazol-1-ylacetate with potassium bromide. Upon heating this compound, ring closure to the zwitterionic 417 takes place in 40% yield. 

Oxidative cyclization of hydrazones to fused [l,2,4]triazoles by means of cupric chloride was already discussed above for a related pyridazine derivative. The same method was also applied successfully for ring closure of 428 to 429 in good to excellent yields (Scheme 53) <2005T5942>. 

Table 20 Ring closures to [1,2,4]triazolo[1,5-a]pyrimidines by reaction of 3-amino[1,2,4]triazoles with /3-oxo ketones, esters, nitriles, or malonic acid derivatives...

Concerning the transformation of substituents, a special note should be made on a series of ring-closure reactions carried out on the side chain of some [l,2,4]triazolo[4,3-r]benzo[l,2,3]triazines published by Moustafa <2001SC97>. The results are summarized in Scheme 18. This scheme shows that by transformation of the R group attached to the sulfur atom of derivative 97 a fairly large set of cyclic products - involving thiazolidone 97a, [l,2,4]triazole 97b, coumarone and its imine 97c and 97d, respectively, benzoxazylpyrane, 97e, thiophene 97f, and cyclopenta- or cyclohexa-fused protected pyrone 97g substituents - have been obtained. 

Several ring-closure reactions for [l,2,4]triazolo[3,4- ][l,3,4]thiadizines have been described, and all these procedures started from 3-mercapto-4-amino[l,2,4]triazole 135 (Scheme 26). A common structural feature of the reagents is the presence of the CH2X (X = halogen atom) moiety which allows the alkylation at the sulfur atom followed by a ring-closure reaction via an elimination step. Some typical ring closures are shown in Scheme 26. 

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