Synthesis of 1,2,4-triazoles and 1,2,4-oxadiazoles

Monothiodiacylamines reacted regiosepecifically with hydrazines and hydroxylamine to give substituted 1,2,4-triazoles and 1,2,4-oxadiazoles in excellent yields.     

1,2,4-Triazines X: Dimerizations of 1,2,4-triazmes

5,5′-Bi-1,2,4-triazinyl compounds are obtained by the treatment of 5-unsubstiluted 1,2,4-triazines with either sodium methoxide or with aqueous potassium cyanide. 5,5′-Bi-1,2,4-triazinyl is also obtained by the reaction of 1,2,4-triazine with potassium cyanide. It is proposed that the sodium methoxide catalyzed dimerizations occur via a carbanionic intermediate; the aqueous potassium cyanide catalyzed reactions via a cyanide addition product and the potassium in liquid ammonia reaction via a free radical dimerization process.     

Synthesis of amino-1,2,4-triazoles by reductive ANRORC rearrangements of 1,2,4-oxadiazoles

The reaction of various 1,2,4-oxadiazoles with an excess of hydrazine in DMF has been investigated. 3-Amino-1,2,4-triazoles are produced through a reductive ANRORC pathway consisting of the addition of hydrazine to the 1,2,4-oxadiazole followed by ring-opening, ring-closure, and final reduction of the 3-hydroxylamino-1,2,4-triazole intermediate. The general applicability of 1,2,4-oxadiazoles ANRORC reactivity is demonstrated also in the absence of C(5)-linked electron-withdrawing groups.     

1,2,4-triazines. 7. Regioselective n2-amination of 3-methylthio-1,2,4-triazin-5(2H)-ones.A novel synthesis of [1,2,4]triazolo[2,3-b][1,2,4]triazinones and -triazine

A regioselective synthesis of 2-aminotriazinones 6a-d is reported, by reaction of 3-methylthio-1,2,4-triazinones 5a-d with O-(2,4-dinitrophenyl)hydroxylamine (2) as an amino-transfer agent. A spectroscopic study and an unequivocal synthesis of 2-amino-4-methyl-6-phenyl-1,2,4-triazinedione ( 11a ) has shown the site of amination to be N2 of the 1,2,4-triazinone ring. Subsequent reaction of 2-amino-1,2,4-triazinones 6a-b with amines, followed by ring closure with aliphatic acids provided [1,2,4]triazolo[2,3-b][1,2,4]triazine-7(1H)ones 13a-e. Conversion of [1,2,4]triazolo[2,3-b][1,2,4]triazinone 13c to unsubstituted [1,2,4]triazolo[2,3-6][1,2,4]triazine (15) was attained.     

Construction of Coplanar Bicyclic Backbones for 1,2,4-Triazole-1,2,4-Oxadiazole-Derived Energetic Materials

Combining different nitrogen-rich heterocycles into a molecule can fine-tune its energetic performance and physical properties as well as its safety for use in energetic materials. Here, 1,2,4-oxadiazole was incorporated into 1,2,4-triazole to construct new energetic backbones. 3-(5-Amino-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazol-5-amine ( 5 ) was designed and synthesized. Nitramino-functionalized N-(5-(5-amino-1,2,4-oxadiazol-3-yl)-3H-1,2,4-triazol-3-yl)nitramide ( 6 ) and N-(5-(5-(nitramino)-1,2,4-oxadiazol-3-yl)-3H-1,2,4-triazol-3-yl)nitramide ( 7 ) were also obtained, and two series of corresponding nitrogen-rich salts were prepared, leading to the creation of new energetic compounds. All derivatives were fully characterized, and five of them were further confirmed by X-ray diffraction. The theoretical calculations, energetic performance, safety, and the main decomposition gaseous products of 1,2,4-triazole-1,2,4-oxadiazole-derived energetic materials were studied. Compound 7 and its dihydroxylammonium salt ( 7 c ) exhibited prominent detonation performance comparable to that of RDX while possessing satisfying thermal stabilities and mechanical sensitivities.     

3,3-Dinitrobutyl-1,2,4-oxadiazoles

The syntheses of 3,5-bis(3,3-dinitrobutyl)-1,2,4-oxadiazole and a series of 3-aryl-5-(3,3-dinitrobutyl)-1,2,4-oxadiazoles were accomplished by treating 4,4-dinitropentanoyl chloride with the appropriate amidoximes to yield the intermediate O-(4,4-dinitropentanoyl)amidoximes, which were dehydrated to the 1,2,4-oxadiazoles.     

Synthesis of 8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine

8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine has been synthesized by the interaction of 6-tert-butyl-3-hydrazino-1,2,4-triazolo[3,4-c]-1,2,4-triazin-5-one with formic acid. The conditions of carrying out the reaction are discussed. Spectral characteristics are given.     

Cyclizations of 1,2,4-triazinium salts with bifunctional nucleophiles - a new route to condensed 1,2,4-triazines

The reaction of 1,2,4-triazinium salts with amides of acetoacetic acid yielding 1,4,4a,5,7,7a-hexahydro-6H-pyrrolo[3,2-e]-1,2,4-triazin-6-ones exemplifies the first direct annelation to the 1,2,4-triazine ring based on the diaddition of bifunctional nucleophiles at C-5 and C-6.     

1,2,4-Oxadiazoles. X. Aryl-1,2,4-oxadiazolecarbaldehydes

The synthesis of 5-aryl-1,2,4-oxadiazole-3-carbaldehydes and 3-aryl-1,2,4-oxadiazole-5-carbaldehydes was attempted through several routes and achieved starting from both the corresponding chloromcthyl and the dichloromethyl derivatives. These aldehydes are stabilized in the hydrated form and this peculiar behavior is discussed on the basis of the relevant spectroscopic data.     

1,2,4-Triazolium-5-ylidene and 1,2,4-triazol-3,5-diylidene as new ligands for transition metals

Ab initio calculations show the 1,2,4-triazolium-5-ylidene (3a) and 1,2,4-triazol-3,5-diylidene (4a) are true minima on the potential surface. As expected, 4a is much higher in energy than its triazole isomers 5a, 6a and 8a and the 1,2,4-triazol-3-ylidene (7a). Sodium methoxyde adds to the diquaternary salt of 1,2,4-triazoles (9b,c) to give the corresponding monocationic heterocycles 10b,c in 70 and 50% yield, respectively. One equivalent of silver(I) acetate reacts with 9b leading to the bis(1,2,4-triazolium-5-ylidene)silver(I) complex (11b) in 80% yield. Under the same experimental conditions, but using two equivalents of silver(I) acetate, solid-state one-dimensional polymers 12′b,c featuring the coplanar 1,2,4-triazol-3,5-diylidene ligands coordinated to silver(I) are obtained in 90% yield. 12′c has been fully characterized including a single-crystal X-ray diffraction study.     

1,2,4-Triazines. 5. Regioselective N2-amination of 3-methylthio-1,2,4-triazin-5(2H)-ones. A new efficient synthesis of [1,2,4]triazolo[2,3-b][1,2,4]triazin-7(1H)-one

A regioselective synthesis of 2-amino-1,2,4-triazinones ( 3a-b ) is reported, by reaction of 3-methylthio-1,2,4-triazinones ( 1a-b ) with O-(2,4-dinitrophenyl)hydroxylamine ( 2 ), as an amino transfer agent. A spectroscopic study and an unequivocal synthesis of 2-amino-4-methyl-6-phenyl-1,2,4-triazinone ( 8a ) has shown the site of amination to be N2 of the 1,2,4,-triazinone ring. Subsequent reaction of 2-amino-1,2,4-triazinone ( 3b ) with ammonium hydroxide, followed by ring closure with formic acid provided [1,2,4]triazolo[2,3-b][1,2,4]triazin-7 (1H)-one ( 10 ).     

Picrylamino-substituted heterocycles. III. 1,2,4-triazoles

This paper describes the synthesis of various picryl-and picrylamino-substituted 1,2,4-triazoles and 3,3′-bi-1,2,4-triazolyls. These compounds were prepared by condensing the appropriate 1,2,4-triazole or amino-1,2,4-triazole with a picryl halide. The proton n.m.r. spectra, crystal densities, thermal stabilities, and drop-weight impact sensitivities of the resulting compounds were determined.     

Synthesis of fluorinated 1,2,4-oxadiazin-6-ones through ANRORC rearrangement of 1,2,4-oxadiazoles

The reaction of 3-ethoxycarbonyl-5-perfluoroalkyl-1,2,4-oxadiazoles with hydroxylamines has been investigated, evidencing the possibility of competitive reaction paths. Nucleophilic addition of hydroxylamine to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring-opening and ring-closure with enlargement, leads to high yield and in very mild experimental conditions to the formation of 5-hydroxyamino-3-perfluoroalkyl-6H-1,2,4-oxadiazin-6-ones, one of these presenting water gelation ability. In turn, reactions with N-methylhydroxylamine lead the exclusive formation of 4-perfluoroacylamino-2-methyl-2H-1,2,5-oxadiazol-3-ones through the well known Boulton-Katritzky rearrangement.     

Comparative theoretical studies on energetic substituted 1,2,4-triazole molecules and their corresponding ionic salts containing 1,2,4-triazole-based cations or anions

We have studied the densities, heats of formation, energetic properties, and thermodynamics of formation for a series of substituted 1,2,4-triazole molecules and their corresponding ionic salts containing 1,2,4-triazolium cations or 1,2,4-triazolide anions using density functional theory and volume-based thermodynamics method. The results show that when the 1,2,4-triazole molecules lose a proton to form corresponding 1,2,4-triazole-based anions, their salts have smaller densities than corresponding molecules. When the molecules get a proton to form the 1,2,4-triazole-based cations, their salts have higher densities than corresponding molecules. The transformation of the 1,2,4-triazole derivatives from nonionic molecules to corresponding cations or anions are very helpful for increasing their heats of formation. Changing the 1,2,4-triazole derivatives into corresponding cations or anions produce different effects on their heats of detonation. Overall, as the compound numbering varies, the evolution trend of heat of detonation is very similar to heat of formation. The salts containing the 1,2,4-triazolide anions have smaller detonation velocities and pressures than corresponding 1,2,4-triazole molecules, whereas the salts containing the 1,2,4-triazolium cations have higher detonation velocities and pressures than corresponding molecules. Finally, the lattice enthalpies and entropies were used to construct a thermodynamic cycle for salt formation to predict the possibility to synthesize the salts.     

1,2,4-Triazines. XII. Syntheses of 5-carboxarnido-1,2,4-triazines via an addition-oxidation reaction

5-Unsubstituted 1,2,4-triazines, when treated with potassium cyanide suspended in moist dioxane afford 5-carhoxamido as well as 5,5′ -bi-1,2,4-triazinyl derivatives. A probable reaction sequence is described.     

Tandem reactions of 1,2,4-oxadiazoles with allylamines

A reaction of 3-chloro-1,2,4-oxadiazoles with allylamine and diallylamine has been investigated. 3,3a,4,5-Tetrahydroisoxazolo[3,4-d]pyrimidines are produced through a tandem ANRORC/[3 + 2]cycloaddition pathway consisting of the addition of allylamine to the 1,2,4-oxadiazole, followed by ring opening, nitrone formation, and finally cycloaddition. 3-N-Allylamino-1,2,4-oxadiazoles were also obtained as minor products through a classical SNAr. Conversely, a reaction with diallylamine produces 3-N,N-diallylamino-1,2,4-oxadiazole and imidazoline through tandem SNAr/aziridination and nucleophilic ring opening.     

Syntheses of substituted-1,2,4-triazoles

Starting from the readily available 3-phenylpropionitrile, 3-(or 5-)(2-phenethyl)-1,2,4-triazole 3 was prepared. Reaction of compounds 3 with diazomethane afforded 1-methyl-3-(2-phenethyl)-1,2,4-triazole (4) and 1-methyl-5-(2-phenethyl)-1,2,4-triazole (5) . Reaction of compound 3 with methanesulfonyl chloride, benzenesulfonyl chloride or p-toluenesulfonyl chloride afforded only one of the expected isomer; namely compounds 6 , 7 and 8 respectively.     

Solid-phase synthesis of 1,2,4-oxadiazoles

The synthesis of 3,5-substituted 1,2,4-oxadiazoles on solid support is described. Benzoic acids bound to the Wang linker on a polystyrene resin are activated and allowed to react with N-hydroxyamidines. The resulting acylated N-hydroxyamidines are converted into 1,2,4-oxadiazoles at 125°C.     

Effect of substituent in pyridine-2-carbaldehydes on their heterocyclization to 1,2,4-triazines and 1,2,4-triazine 4-oxides

A series of substituted pyridine-2-carbaldehydes were brought into heterocyclization with isonitrosoacetophenone hydrazones, followed by aromatization by the action of oxidants or by dehydration in boiling acetic acid. As a result, substituted 3-(pyridin-2-yl)-1,2,4-triazines or 3-(pyridin-2-yl)-1,2,4-triazine 4-oxides were formed. 6-Formylpyridine-2-carbonitrile failed to undergo heterocyclization, 6-methylpyridine-2-carbaldehyde and methyl 6-formylpyridine-3-carboxylate can be converted to both 1,2,4-triazine and 1,2,4-triazine 4-oxide derivative, and only 1,2,4-triazine 4 oxides were obtained from 6-bromopyridine-2-carbaldehyde and 6-formyl-3-phenylpyridine-2-carbonitrile. Convenient procedures were proposed for the synthesis of some initial pyridinecarbaldehydes.     

Synthesis of 1-alkyl-1,2,4-triazolium 4-nitroimides by alkylation of 4-nitramino-1,2,4-triazole salts

A method for the synthesis of 1-alkyl-1,2,4-triazolium 4-nitroimides was developed based on alkylation of 4-nitramino-1,2,4-triazole Na and Ag salts with halo- and dihaloalkanes.