1.2.4- Triazoles, condensed

Aryl-5-mercapto-1,2,4-triazoles condense with anthranilic acid forming 3-ary 1-5,6-benzo-7-oxo-TPs [82IJC(B)377],... 

Oxadiazoles have been utilized in the synthesis of 1,2,4-triazoles. Condensation of highly reactive chloromethyloxadiazoles 171 with ethylenediamines 172 afforded amidines 173, which under reflux in methanol, gave [l,2,4]triazolo[4,3-a]piperazines 174 <050L1039>. Reaction of... 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

Phenylisoxazolin-5-one condensed with anthranal to give a tricyclic isoxazolylquinoline (Scheme 72) <78CZ264). 3-Methyl-4-phenylazoisoxazoline-5-thione reacted with ethyl chloroacetate for form an intermediate isoxazolethiol, which on heating generated a 1,2,3-triazole (Scheme 73). 

EINHORN - BRUNNER Tria2ole Synthesis Condensation of hydrazines with diacyctamines (imidea) to triazoles... 

OOOKGSlOO) (Scheme 134). Triazolylfurazans 207 were also prepared by condensation of azidofurazans with active methylene compounds in the presence of MgCOs (99MI1). A variety of azidofurazans and -furoxans reacted similarly to form the corresponding triazole derivatives. 

Condensation of 2-azido benzonitrile derivatives 703 with ethyl aeetonediearboxylate in presenee of NaOEt gave the triazoloquinoline derivatives 705 presumably through the intermediate 704 (90S654). Reaetion of 703 with dibenzyl ketone gave the triazole 706 aeeompanied by 707 whieh upon treatment with NaH in THF afforded 706 (97S773) (Seheme 122). 

The condensed l//-l,2-diazepines 12 are transformed into the 3//-tautomers 24 by reduction with lithium aluminum hydride to give 23, followed by dehydrogenation with 4-phenyl-4//-1,2,4-triazole-3,5-dione.146... 

Acenaphtheno[l,2-e][l,2,4]triazolo[4,3-h][l,2,4]triazine 747 was prepared (79AP147) by cyclizing 3-hydrazinoacenaphtheno[l,2-e][l,2,4]tria-zine 746 with formic acid. Reaction of 746 with sugars gave the hydrazones, which cyclized with iron(III) chloride to give 748 (93BCJ00). Similarly, the acetaldehyde derivative of 746 was cyclized to 748. The structure of 748 (R = Me) rather than 747 (R = Me) was deduced by unequivocal synthesis of the latter by condensation of acenaphthenequinone with 3,4-diamino[l,2,4]triazole (Scheme 155). 

The action of hydrazine on l-acetonyl-5-chloro[l,2,4]triazole 777 or 778 gave (77JOC1018 82KGS1113) 779 and 780, respectively. Dehydrogenation of 779 gave 781. Condensation of 3-hydrazino[l,2,4]triazole 782 with... 

Process development of the synthesis of iodoaniline 28 began with an improved synthesis of l-(4 -aminobenzyl)-l,2,4-triazole (6) (Scheme 4.7), which was prepared in the medicinal chemistry synthesis, albeit with poor regioselectivity (Scheme 4.1). We found that this aniline intermediate 6 could be readily prepared in three steps in >90% overall yield from 4-amino-l,2,4-triazole (30) and 4-nitrobenzyl bromide (4) based on a modified literature procedure [9]. The condensation of 30 and 4 in isopropyl alcohol followed by deamination gave the nitro... 

Using method a, oligodeoxyribonucleotides were synthesized from di- to deca-deoxyribonucleotides by means of mesitylenesulfonylimidazole and mesitylenesulfonyl-1,2,4-triazole. With triisoproylbenzenesulfonylimidazole die condensation took place more slowly.11121 Compared widi the corresponding arylsulfonyl chlorides, imidazolides induced intemucleotide condensation much more slowly, but caused no darkening of the reaction mixture, did not affect acid-sensitive bonds in trityl protected nucleotides, and did not sulfonate the 3 -hydroxy groups.11111 The reaction conditions were room temperature, 5—6 days, and pyridine as solvent.11111... 

In ref. [127] an investigation was made on the rate of phosphortriester formation and the percentage of sulfonated products in the cases of mesitylenesulfonyl-3-nitro-1,2,4-triazole (V), 2,4,6-triisopropylbenzenesulfonyltetrazole, and 2,4,6-triisopropylbenzene-sulfonyl-3-nitro-1,2,4-triazole (VI) as condensing agents. 

Comparing reaction times and yields for the condensing agents 1-triisopro-pylbenzenesulfonyl-4-nitroimidazole, mesitylenesulfonyl-3-nitro-1,2,4-triazole, 1 -triiso-propylbenzenesulfonyl-3-nitro-1,2,4-triazole, and 8-quinolinesulfonyl-3-nitro-1,2,4-triazole, the latter showed the highest yield and shortest reaction time. A fully protected 2, 5 -trinucleotide diphosphate was also successfully synthesized by means of a mixture of 8-quinolinesulfonyl chloride and 3 -nitro-1,2,4-triazole,[ 1421... 

If CDI is employed as imidazolide, methyl 2,4,6-trihydroxybenzoate is obtained in 47% yield. Propionyl-1,2,4-triazole behaves in the same way as the imidazolides, giving similar yields (50%), but the benzotriazolides and benzimidazolides were not as effective. The o-nitrophenyl and p-chlorophenyl esters of propionic acid did not lead to any aromatic products.11185 Similar 5C + 1C condensation reactions are described in references [119] and [120],... 

Reaction of the spirocyclic imidazoline 316 with glyoxal and sodium hydrogen sulfite results in hydrolysis of the aminal and subsequent double condensation to give the tetrazolopyridopyrazine 317 (Equation 109) <1999JHC117>. The pyridopyridazinylhydrazine 318 can be cyclized to the fused triazole 319 by reaction with formic acid (Equation 110) <1998SC2871>. 

The preparation of condensed rhodacyclopentadienes via the diyne reaction, and examples of their use in heterocyclic synthesis have been described earlier (see Schemes 79 and 86 in Sections IV,B,5 and IV,C,2). An example showing the application of this approach to the synthesis of a condensed triazole is shown in Scheme 127.192... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Condensation of benzaldehydes with benzotriazole in the presence of thionyl chloride readily gives a,a-/fe(benzo-triazol-l-yl)toluenes 727 that can be considered as l,l -gm-dicarbanion equivalents. Thus, treatment of derivatives 727 with ketones and lithium metal suspended in THF at — 78 °C generates substituted propylene glycols 728 (Equation 18) <1998TL2289>. 

Condensation of diazonium salts 1152 with activated nitriles provides hydrazones 1153. Treatment of hydrazones 1153 with hydroxylamine affords amidoximes 1154 in high yield. Upon heating with anhydrous sodium acetate in refluxing DMF, compounds 1154 undergo intramolecular cyclocondensation to provide 5-substituted 4-amino-2-aryl-277-1,2,3-triazoles 1155 in 75-85% yield (Scheme 190) <2006ARK(xv)53>. 

It appears that treatment of phenacyl bromides 1239 with methylhydrazine in refluxing acetic acid leads also to 1,4-disubstituted triazoles 1244. Fivefold excess of methylhydrazine is used in these reactions. According to the proposed mechanism, structures 1240-1243, methylhydrazine has a double role, as a condensing agent and an oxidant. In the final account, three molecules of methylhydrazine have to be used to produce one molecule of triazole 1244, two molecules of methylamine and one molecule of ammonia. The basic triazole 1244 (X = Y = H) is separated in 59% yield. The reactions go well with electron-donating substituents (for X = OH, the yield is 81%), but electron-withdrawing substituents can lower the yield dramatically (11% for X = N02) (Scheme 206) <2003JCM96>. 

The synthesis of 4,5-disubstituted triazoles shown in Scheme 208, carried out on a polymer support with microwave assistance, is based on a similar principle. In the first step, sulfinate 1248 is converted to sulfone 1249. Condensation with aldehydes provides vinyl sulfones 1250. Cyclocondensation of sulfones 1250 with sodium azide generates corresponding triazoline intermediates that eliminate sulfinate 1248 to provide triazoles 1251 in moderate to good yield <2006OL3283>. 

Arylhydrazonoacetamides 155 undergo acid-catalyzed condensation with ketones to give the corresponding 4,5-dihydro-1,2,4-triazoles 156a-m in good yields (Equation 48 and Table 30) <2002T5317>. 

---