Five-to-six membered ring-rearrangements in the reaction of 5-perfluoroalkyl-1,2,4-oxadiazoles with hydrazine and methylhydrazine

The hydrazinolysis reaction of 5-perfluoroalkyl-1,2,4-oxadiazoles with hydrazine or methylhydrazine as bidentate nucleophiles has been investigated. The reaction occurred through the addition of the bidentate nucleophile to the C(5)-N(4) double bond of the 1,2,4-oxadiazole followed by ring-opening and ring-closure (ANRORC) involving the second nucleophilic site of the reagent. This ring-closure step could involve either the original C(3) of the 1,2,4-oxadiazole (giving a five-to-five membered ring rearrangement) or an additional electrophilic center linked to it (exploiting a five-to-six membered ring rearrangement). An alternative initial nucleophilic attack may involve the additional electrophilic center linked at C(3), that is the carbonyl group, leading to the formation of the hydrazones which undergo the Boulton-Katritzky rearrangement (BKR). The chosen reaction path is a function of the used nucleophile and of the nature of the substituent at C(3). At variance with previous hypotheses, when methylhydrazine was used, the observed regiochemistry always showed the preferred initial attack by the less hindered NH(2) end of the nucleophile on C(5). Moreover, new spectroscopic evidence allowed the assignment of correct structures to the products formed by reaction of 5-perfluoroalkyl-3-phenyl-1,2,4-oxadiazoles with methylhydrazine.     

Fluorinated heterocyclic compounds. An expedient route to 5-perfluoroalkyl-1,2,4-triazoles via an unusual hydrazinolysis of 5-perfluoroalkyl-1,2,4-oxadiazoles: first examples of an ANRORC-like reaction in 1,2,4-oxadiazole derivatives

The hydrazinolysis reaction of 5-perfluoroalkyl-1,2,4-oxadiazoles has been investigated. Nucleophilic addition of the reagent to the C(5)-N(4) double bond of the oxadiazole ring, followed by ring-opening and then ring-closure involving the beta-nitrogen atom of the hydrazino moiety and the C(3) of the oxadiazole ring, explains the formation of 5-perfluoroalkyl-1,2,4-triazoles as final products. Useful applications in synthesis of this uncommon hydrazinolysis can be claimed.     

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.     

Synthesis,reactions and biological evaluation of some 1,2,4-triazine derivatives

6-Substituted benzyl-4-phenyl-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-5-ones 3a-d were prepared and converted into their corresponding 3-methylthio derivatives 4a-d . Reaction of compounds 4a-d with hydrazine hydrate gave the corresponding 4-amino-3-anilino-4,5-dihydro-1,2,4-triazin-5-ones 5a-d . 6-Substituted benzyl-4-phenyl-2,3,4,5-tetrahydro-1,2,4-triazin-3,5-diones 9a-c were synthesized and allowed to react with hydrazine hydrate to give the corresponding 6-substituted benzyl-4-amino-2,3,4,5-tetrahydro-1,2,4-triazin-3,5-diones 10a-c . The biological evaluation of some of these triazines is described. All compounds were screened for antiviral, antibacterial, antimycobacterial, antifungal and antiyeast activity. No important biological activity was found.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Photochemistry of 1,2,4-oxadiazoles. A DFT study on photoinduced competitive rearrangements of 3-amino- and 3-n-methylamino-5-perfluoroalkyl-1,2,4-oxadiazoles

The photoinduced competitive rearrangements of 5-perfluoroalkyl-3-amino(N-alkylamino)-1,2,4-oxadiazoles have been investigated by DFT calculations and UV-vis spectroscopy. The observed product selectivity depends on the number of hydrogen atoms present in the amino moiety and involves two or three possible routes: (i) ring contraction-ring expansion (RCRE), (ii) internal-cyclization isomerization (ICI), or (iii) C3-N2 migration-nucleophilic attack-cyclization (MNAC). UV absorption and fluorescence spectra of the reactants, and vertical excitation energy values, calculated by time dependent DFT, support the involvement of a neutral singlet excited state in the photoexcitation process. The values of the standard free energy of the most stable prototropic tautomers of reactant, products, proposed reaction intermediates, and deprotonated anionic transition states allowed us to rationalize the competition among the three rearrangements, in agreement with chemical trapping experiments, in terms of: (i) the evolution of the excited state toward three stable ground-state intermediates, (ii) tautomeric and deprotonation equilibria occurring in methanol solution for each intermediate, and (iii) relative stabilization of intermediates and transition states in the thermally driven section of the reaction.     

A new method for the synthesis of novel 1-aryl-3-quinoxalinyl-1,2,4-triazol-5-ones

The reactions of 3-methoxycarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline 1 with aryl diazonium salts gave 3-(α-aryldiazenylmethoxycarbonylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines 2a-c , whose reactions with hydrazine hydrate afforded 3-(α-aryldiazenylhydrazinocarbonylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines 3a-c . The reactions of 3a-c with nitrous acid resulted in the Curtius rearrangement to provide the 1-aryl-3-quinoxalinyl-1,2,4-triazol-5-ones 4a-c.     

A short and general synthesis of 1,3-dihydro-6-heteroaryl-5-perfluoroalkyl-2H-imidazo[4,5-b]pyridin-2-ones

Trifluoro or pentafluoroacylation of heteroaryl-enamines 2a,b gave the corresponding perfluoroacylated heteroaryl-enamines 3a-c . Heating the latter compounds with diethyl iminomalonate gave 2-amino-3-pyridinecarboxylates 4a-c . Hydrolysis to the free acids 5a-c , and reaction with diphenylphosphoryl azide afforded the desired 1,3-dihydro-6-heteroaryl-5-perfluoroalkyl-2H-imidazo[4,5-b]pyridin-2-ones 6a-c .     

Synthesis and Transformations of 2-R-5-Aryl-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin-7-ones

A new procedure for preparation of 2-R-5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 5-R-1,2,4-triazole-3-thiones with 3-arylacryloyl chlorides was developed. The thiazine ring of the [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones is easily cleaved by treating with ammonia and hydrazine affording amides and hydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids. The latter react with isothiocyanates furnishing carbamoyl thiohydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids that in alkaline media undergo cyclization into 4-aryl-5-[2-(4H-1,2,4-triazol-5-ylsulfanyl)-2-phenylethyl]-2,4-dihydro-3H-1,2,4-triazole-5-thiones.     

Study of the Products of Iodocyclization of 4-Allyl-5-phenyl-1,2,4-triazole-3-thione

The interaction of 4-allyl-5-phenyl-1,2,4-triazole-3-thione with iodine proceeds with the formation of a mixture of 6-iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole and 6-iodo-3-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine. The structures of the cyclization products obtained were established on the basis of the ¹H NMR spectra of their dehydroiodinated derivatives. 6-Methyl-3-phenylthiazolo[2,3-c]-1,2,4-triazole, 3-phenyl-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine, and 3-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3-thiazine are formed on eliminating HI from the cyclization products.     

Synthesis of 1,3,5-Trisubstituted 1H-1,2,4-Triazoles Containing Hetaryl Fragments

N¹-Phenyl- and N¹-(3,5-dichloro-2-pyridyl)amidrazones have been synthesized by the reaction of imino esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine. Acylation of the products with acid chlorides leads to 1-phenyl- and 1-(3,5-dichloro-2-pyridyl)-3-hetaryl-5-R²-1H-1,2,4-triazoles. Compounds of this type are also formed by the condensation of N-acylimino esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine.     

The first 1-alkyl-3-perfluoroalkyl-4,5- dimethyl-1,2,4-triazolium salts

Syntheses of quaternary 1-alkyl-3-perfluoroalkyl-4,5-dimethyl-1,2,4-triazolium iodides have led to a variety of new quaternary salts via metathesis reactions. 1,4,5-Trimethyl-3-trifluoro-methyl-1,2,4-triazolium iodide (6) with LiN(SO(2)CF(3))(2), KSO(3)CF(3), AgClO(4), AgBF(4); 1-(3-fluoropropyl)-3-trifluoromethyl-4,5-dimethyl-1,2,4-triazolium iodide (7) with LiN(SO(2)CF(3))(2); and 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium iodide (8) with LiN(SO(2)CF(3))(2), AgClO(4), AgBF(4) gave excellent yields of new thermally stable and relatively low melting quaternary salts. The structure of 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium tetrafluoroborate (11c) was confirmed by single-crystal X-ray analysis. Although the molecular weight of 11c (cation) is 3-fold greater than that of the 3-trifluoromethyl derivative 9d, its melting point is 32 degrees C lower.     

1,2,4-三嗪类化合物的研究XXI.3-甲硫基-5-氧代-2.5-二氧-1,2,4-三嗪的取代苯磺铣化反应及6- 碳的亲电特性

3-甲硫基-5-氧代-2.5-二氧-1,2,4-三嗪(Ic)与取代的苯磺铣氯反应,在无水吡啶中生成N-[6-(3-甲硫基-5-负氧基)-1,2,4-三嗪基]吡啶内嗡盐(4);在NaOH-H~2O-Ch~3COCH~3中生成3-甲硫基-4-(取代苯磺铣基)-5-氧化-6-羟基-1,4,5,6-四氢- 12,4-(6);资Naoh-Ch~3O中则生成1-(对甲苯磺铣基)-3-甲硫基-6-甲氧基-1,4,5,6-四氢-三嗪(7)显示了其6-C具有不寻常的亲电特性.     

Ring-transformation of 1,2,4-oxadiazines. Raney nickel hydrogenation of Z-3-aryl-5,6-dihydro-5-(substituted)methylene-4H-1,2,4-oxadiazine derivatives

Raney nickel hydrogenation of Z-3-aryl-5-(ethoxycarbonyl)methylene-5,6-dihydro-4H-1,2,4-oxadiazine ( 1a-c ) affords 2-aryl-6-hydroxymethyl-4-pyrimidinone ( 2 ) and ethyl (2-aryl-4-oxazolyl)acetate ( 3 ). A similar hydrogenation of Z-5-arylcarbarnoyl)methylene-5,6-dihydro-3-phenyl-4H-1,2,4-oxadiazine ( 1d-f ) gives E-4-(arylcarbamoyl)methylene-2-phenyl-2-oxazoline ( 5 ), 4-(arylcarbamoyl)methyl-2-phenyloxazole ( 6 ), and Z-4-(aryl-carbamoyl)methylene-2-phenyl-2-oxazoline ( 7 ).     

One-pot synthesis of imidazo[1,2-b]pyrazole,imidazo[1,2-b]-1,2,4-triazole,imidazo[1,2-a]pyridine,imidazo[1,2-a]pyrimidine,imidazo[1,2-a]benzimidazole,and 1,2,4-triazolo[4,3-a]benzimidazole derivatives

Hydrazonoyl bromides 1a-c react with 5-amino-3-phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2-aminopyridine, and 2-aminobenzimidazole to afford the corresponding imidazol[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2-a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21. © 1997 John Wiley & Sons, Inc.     

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 ).     

Synthesis and Anti-Inflammatory Properties of Substituted 5-(Tetrahydro-4-phenyl-2H-pyran-4-yl)-4H-1,2,4-triazole-3-thiols

Russian Journal of Organic Chemistry - 5-(Tetrahydro-4-phenyl-2H-pyran-4-yl)-4H-1,2,4-triazole-3-thiol was synthesized by the reaction of 4-phenyltetrahydropyran-4-carbonyl chloride with...     

Synthesis of new bis-1,2,4-triazole derivatives

A series of new 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 4 were prepared in good yields by treatment of 4-amino-3-aryl-5-phenyl-4H-1,2,4-triazoles 2 with certain bis-aldehydes 1.Compounds 4 were reduced with NaBH(4) to afford the corresponding 1,2/1,3-bis[o-(N-methylamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 5. All new compounds were characterized by IR, (1)H-NMR, (13)C-NMR and mass spectral data.     

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.     

含吡唑1,2,4-三唑噻二嗪衍生物的合成及抑菌活性

1-苯基-3-甲基-5-氯-4-吡唑甲醛与4-氨基-5-取代苯基-1,2,4-三唑-3-硫酮缩合生成4-(1-苯基-3-甲基-5-氯吡唑次甲亚胺基)-5-(取代苯基)-2H-1,2,4-三唑-3(4H)-硫酮,再烷基加成化为新型含吡唑基5,6-2H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪衍生物。 化合物结构经¹H NMR、IR以及元素分析确认。 初步生物活性测试结果表明,在100 mg/L浓度下,化合物8a(3-(2-甲基苯基)-6-(5-氯-2-甲基-4-苯基吡唑)-7-(4-硝基苯基)-5H-1,2,4-三唑[3,4-b][1,3,4]噻二嗪)对黄瓜炭疽病的抑制率达90%。