On triazoles. XVII . The reaction of 5-amino-1,2,4-triazoles with N-heterocyclic β-oxo-esters

Pyrrolo[3,4-d]-1,2,4-triazolo[1,5-a]pyrimidinone ( 3d ), pyrido[3,4-d]-1,2,4-triazolo[1,5-a]pyrimidinone ( 3e ) and pyrido[4,3-e]-1,2,4-triazolo[1,5-a]pyrimidinone ( 4e ) derivatives representing three new ring systems were synthesised. Their structure was proved by comparing their uv and cmr spectra with those of the known benzo- and thieno-1,2,4-triazolo[1,5-a]pyrimidinones used as model compounds.     

On triazoles. X. The reaction of 5-amino-1,2,4-triazoles with tetrahydrothiophene β-keto esters

Three novel ring systems, namely the thieno[3,4-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thieno[3,4-e]-1,2,4-triazolo[1,5-a]pyrimidine and the thieno[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidine were synthesised. The structure of compounds obtained was proved with the help of their uv and cmr spectra using model compounds prepared for this purpose.     

On triazoles XVI. The reaction of 5-amino-1,2,4-triazoles with β- and γ-oxo esters. A novel N-carbonylation reaction

5-Amino-1,2,4-triazoles reacted with alifatic β-oxo-esters to yield besides the unexpected 1,2,4-triazolo-[1,5-a]-1,3,5-benzotriazepin-5-one derivative 7 either the corresponding esters 5 and 6 or a 1:2 condensation product 8. To the contrary alicyclic and heterocyclic β-oxo-esters formed in the above reaction only derivatives 7. The proposed mechanism of the formation of 7 involving a novel N-carbonylation reaction was proved by the isolation of the by-products and the intermediate of the reaction. Repeating the above reaction with a γ-oxo-ester, namely the ethyl levulinate, derivatives 17 and 18 , respectively, representing two new ring systems were obtained.     

On Triazoles. XXXII. The reaction of 5-amino-1 H-1,2,4-triazolylcarbothiohydrazides with β- and γ-oxo-esters

5-Amino-lH-1,2,4-triazolylcarbothiohydrazides gave β and γ-oxo-esters in boiling ethanol [1,2,4]triazolo- [1,5-d][1,2,4,6]tetrazepine-5-thiones 3 . Analogously ethyl 2-oxocyclohexanecarboxylate provided a mixture of two diastereomeric spiro derivatives 5 and 6 . At 130°, 2-acetonyl-5-methyl-4,5-dihydro-1,3,4-oxadiazole-5-thione ( 8 ) was formed. Ring closure of 3e (R¹ = CH₃, R² = CH₂CH₂COOEt, Q = morpholino) lead to the isomeric pyrrolo[2,1-g][1,2,4]triazolo[1,5-d][1,2,4,6]tetrazepin-8(11H)-one ( 12 ) and pyrrolo[1,2-f][1,2,4]triazolo-[1,5-d][1,2,4,6]tetrazepin-10(7H)-one ( 13 ) derivatives representing two new ring systems.     

On triazoles XXIII [1]. The reaction of 5-amino-1,2,4-triazoles with thiacyclohexane β-oxo esters [2]

Six novel isomeric ring systems, namely the thiopyrano[4,3-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,4-e]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,4-d]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[4,3-e]-1,2,4-triazolo[1,5-a]pyrimidine, the thiopyrano[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidine and the thiopyrano[2,3-e]-1,2,4-triazolo[1,5-a]pyrimidine were synthesised. Spectroscopical evidence was given for the structure of compounds obtained.     

On triazoles. XXXV. The reaction of 5-amino-1,2,4-triazoles with di- and triketones

The reaction of 5-amino-3-Q-1H-1,2,4-triazoles 1 with aliphatic, aromatic and cyclic 1,3-diketones, 1,4-diketones, and different linear and non linear triketones was studied. It was proved that in case of unsym-metrical aliphatic 1,3-diketones the regiochemical outcome of the reaction was influenced by steric factors. In case of triacetylmethane and 3-(4-chlorobenzyl)-2,4-pentanedione the splitting of one acetyl group from the reactant was observed during the reaction. A liner triketone, namely the 2,4,6-trioxoheptane reacted as a simple 1,3-diketone.     

On triazoles. VIII The reaction of 5-amino-1,2,4-triazoles with ethyl 2-cyano-3-ethoxyacrylate and 2-cyano-3-ethoxyacrylonitrile

The reaction of different 5-amino-3-Q-1H-1,2,4-triazoles 1 with ethyl 2-cyano-3-ethoxyacrylate ( 5a ) and 2-cyano-3-ethoxyacrylonitrile ( 5b ) to yield either the a type 5-amino-, or the b type 7-amino-1,2,4-triazolo[1,5-a]-pyrimidine derivatives 6–10 was studied. The structure of compounds 6 and 9 was proved by their degradation to the corresponding derivatives 17a and 18a , respectively, through intermediates 11a, 12a, 13a, 14a, 15a and 16a , respectively. The structure of derivatives 7, 8 and 10 was proved on the basis of the analogy of their uv spectra with those of 6a and 9a , respectively. The isolation of the intermediates 19 and 20 helped to prove the mechanism of the reactions leading to the formation of 6a and 9a , respectively. In the reaction of the N-substituted 5-amino-1,2,4-triazoles with 5a the expected condensed ring products were not formed. Instead the aminoacrylates 22 and 24 were obtained. The “Z”-“E” isomeric structure of derivatives 19, 20, 22 and 24 was proved with the help of their pmr spectra. The “Z” isomeric structure of the thermodynamically stabile 22 was corroborated with the help of its proton coupled cmr spectra, too.     

On triazoles XIX: The reaction of 5-amino-1,2,4-triazoles with functionalized acetoacetic esters

Summary Different functionalized alkyl 3-oxo-butyrates (2) were reacted with 5-amino-3-Q-1H-1,2,4-triazoles (1) to yield3 and4 type 1,2,4-triazolo[1,5-a]pyrimidinones. In case of2 (R ¹=methyl,R ²=1-ethoxycarbonylethyl,R ³=ethyl) beside the corresponding derivative4 the unexpected 5,6-dihydro-6,8-dimethyl-7-ethoxycarbonyl-3-methylthio-1,2,4-triazolo[4,3-a]-1,3-diazepin-5(9H)-one (7) was isolated, representing a novel ring system.

---

Über Triazole, 19. Mitt.: Die Reaktion von 5-Amino-1,2,4-triazolen mit funktionalisierten Acetoessigestern

Zusammenfassung Verschiedene funktionalisierte 3-Oxo-buttersäurealkylester (2) wurden mit 5-Amino-3-Q-1H-1,2,4-triazolen (1) umgesetzt, wobei 1,2,4-Triazolo[1,5-a]pyrimidinone der Typen3 und4 erhalten wurden. Im Fall von2 (R ¹=Methyl,R ²=1-Ethoxycarbonylethyl,R ³=Ethyl) wurde neben dem erwarteten Derivat4 das unerwartete 5,6-Dihydro-6,8-dimethyl-7-ethoxycarbonyl-3-me-thylthio-1,2,4-triazolo[4,3-a]-1,3-diazepin-5(9H)-on (7) isoliert, welches ein neues Ringsystem darstellt.

     

On triazoles. XII. The carbamoylation and thiocarbamoylation of 5-amino-1,2,4-triazoles

The reaction of 5-amino-3-R-1H-1,2,4-triazoles 1 with isocyanates 2 (X = O) and isothiocyanates 2 (X = S) was studied. It was stated that with isocyanates 3a (X = O) type ring-carbamoylated products were formed which did not rearrange to the corresponding exo-carbamoylated derivatives 6a (X = O). On the other hand the thiocarbamoylation of derivatives 1 provided at mild conditions lead to derivatives 3a (X = S) which could be rearranged by heating to derivatives 6a (X = S). In one case the isomeric 4a (X = S) type derivative was also isolated. The comparison of the ir, uv, pmr and cmr spectra of the isomers isolated with the corresponding spectra of the carbamoylated and thiocarbamoylated 3,5-diamino-1,2,4-triazole derivatives helped to prove unequivocally the isomeric and tautomeric structure of compounds obtained giving a possibility to correct many confusions in the literature.     

On triazoles. V. Synthesis of 1- and 2-R1-3-R2,R3-amino-5-amino-1,2,4-triazoles

The correct isomeric and tautomeric structure of different 1- and 2-R¹-3-R²,R³-amino-5-amino-1,2,4-triazole derivatives prepared from the corresponding N-cyano-N'-R²,R³-S-methyl-isothioureas and the corresponding hydrazines was proved with the help of their ir, uv, ¹H-nmr and ¹³C-nmr spectra as well as the uv spectra of the Schiff bases of an isomeric pair.     

On triazoles XXXVIII. The reaction of isomeric 5-amino-3-morpholino-1H-1,2,4-triazolylcarbothiohydrazides with ortho esters

The reaction of isomeric differently methylated 5-amino-3-morpholino-1H-1,2,4-triazolylcarbo-thiohydrazides with ortho esters were studied. Except of the case of triethyl orthoacetate instead of the expected [1,2,4]triazolo[1,5-d][1,2,4,6]tetrazepin-5(7H)-thione ( 6 ) derivatives different rearranged products such as 7, 8, 21, 23, 25 , and 27 were obtained, derivatives 23 and 27 representing a novel ring system. Possible explanations were given for the formation of the rearranged products.     

Reaction of 3-oxo-N-phenylbutanethioamide with 5-amino-1H-1,2,4-triazoles

Reactions of 3-oxo-N-phenylbutanethioamide with 3-substituted 5-amino-1H-1,2,4-triazoles in acetic acid led to the formation of 5-methyl-7,8-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7-thiones, 7-methyl-5,8-dihydrol[1,2,4]triazolo[1,5-a]pyrimidine-5-thiones and 7-methyl-5-phenylamino[1,2,4]triazolo[1,5-a]pyrimidines. The structure of the products was proved by the ¹H and ¹³C NMR spectra, X-ray diffraction data, and chemical transformations.     

On Triazoles. VI. The acylation of 5-amino-1,2,4-triazoles

The isomeric and tautomeric structure of I and II type monoacylated 5-amino-1,2,4-triazole derivatives was studied with the help of their ir, uv, pmr and cmr spectra as well as model compounds prepared for this purpose. It was stated that the structure of the I type ring-acylated derivatives is 2o and those of their II type isomers is 5a .     

On triazoles. XXV. The reaction of methyl (5-amino-3-Q-1H-1,2,4-triazolyl)dithiocarbonates with amines

Different “functionalised” triazolylthioamides 3 and -thioureas 4 were synthesised. The ring closure of the ω-hydroxyalkylthioamides 3/2–5 led to the corresponding 2-thiazoline 5/2–4 and 5,6-dihydro-4H-1,3-thiazine 5/5 derivatives, respectively. Unexpectedly, the ring closure of the corresponding 2,2-dimethoxyethyl derivative 3/18 led depending on the reaction conditions to a thiazole derivative 6 or to its 1,2,4-triazolo[3,4-b]-1,3,5-triazepin-5(9H)-thione isomer 7 representing a novel ring system. To corroborate its structure 7 was methylated to the corresponding S-methyl derivative 8 . Spectroscopical evidence is given for the structure of derivatives 3–8 obtained.     

On the lead tetraacetate oxidation of 4-amino-1,2,4-triazoles, 1-amino- and 2-amino-1,2,3-triazoles

Lead tetraacetate oxidation of 4-amino-1,2,4-triazoles, 1-amino- and 2-amino-1,2,3-triazoles affords mainly fragmentation to nitriles or acetylenes, even in the presence of intramolecularly attached double bonds.

---

Über die Bleitetraacetatoxidation von 4-Amino-1,2,4-triazolen, 1-Amino- und 2-Amino-1,2,3-triazolen (Kurze Mitteilung)

Zusammenfassung Bei der Oxidation von 4-Amino-1,2,4-triazolen, 1-Amino- und 2-Amino-1,2,3-triazolen mit Bleitetraacetat entstanden hauptsächlich Nitrile bzw. Acetylene durch Fragmentierung — trotz der Gegenwart von intramolekularen Doppelbindungen.

     

Crystal structures of an isomeric pair of 3-methylthio-5-amino-1,2,4-triazoles

The structures of an isomeric pair: 1-[2-(2,6-dichlorophenoxy)-ethyl]-3-methylthio-5-amino-1H-1,2,4-triazole (IV) and 2-[2-(2,6-dichlorophenoxy)-ethyl]-3-methylthio-5-amino-2H-1,2,4-triazole (V) have been established by X-ray crystallography from diffractometer data. Crystals of IV are monoclinic, space group P2₁/c with a = 11.220(1), b = 10.005(3), c = 12.784(3) Å, β = 91.99(1)°, Z = 4, D_c = 1.478 g cm⁻³. Crystals of V are orthorhombic, space group Pbca with a = 7.618(2), b = 14.289(4), c = 26.494(7) Å, Z = 8, D_c = 1.470 g cm⁻³. The structures determined by direct methods were refined to R = 0.060 for 1931 reflections of IV and R = 0.061 for 1315 reflections of V. The X-ray analysis corroborated the structures assigned to the isomeric pair on the basis of proton coupled ¹³C-NMR spectra. The features (i.e. the sequence of the endocyclic bond angle magnitudes) of the planar s-triazole rings are governed by the same rules reported recently by Kálmán and Argay [J. Mol. Struct., 102 (1983) 391] discussing the structures of the related I, II and III compounds. In contrast to I, II, III and IV the S(6)---C(7) bond of V is almost perpendicular to the best plane of the s-triazole ring C(7)---S(6)---C(3)---N(4) = −79.0(7)°. This unusual orientation of the S-methyl bond is created by the steric hindrance of the very same vicinal 2-ethyl (C(9)H₂---C(10)H₂) moiety once within the molecule V and the second time as the part of a symmetry equivalent molecule at a distance of −a (7.618 Å). These molecules are fixed together by two infinite helices of hydrogen bonds formed around the screw axis 2, (X, 1/4, 1/2) via an intermediate V molecule at (x − 1/2, 1/2 − y, 1 − z).     

Ring-degenerate rearrangement of 5-amino-4-iminomethyl-1, 2, 3-triazoles

5-Amino-4-(substituted)iminomethyl-1-phenyl-1, 2, 3-triazoles 5 rearrange thermally to 4-amidino-substituted triazoles 6 instead of undergoing the Dimroth rearrangement to 5-anilinotriazoles 3 .     

Triazoles. III. The alkylation of 3-R′-thio-5-amino-1,2,4-triazoles

The alkylation of 3-R′-thio-5-amino-1H-1,2,4-triazoles 1 or their sodium salt with alkyl and aralkyl halides 2 , respectively, to yield all the four possible monoalkylated derivatives 3, 4, 5 and 6 was studied. The comparison of the spectral data of different type isomers 3, 4, 5 and 6 isolated and their Schiff bases 8, 9 and 10, respectively, was unequivocal evidence in support of their structure which was then further supported by independent synthesis and ring closure reactions. According to an hplc study the main product of the alkylation is derivative 3 , the by-product is derivative 4 , while derivatives 5 and 6 are formed only in insignificant amounts.     

Conversion of 2-amino-5-R-phenyl-1,3,4-oxadiazoles into 3-R-phenyl-5-alkoxy-1,2,4-triazoles

2-Amino-5-R-phenyl-1,3,4-oxadiazoles have been shown to isomerize in alcoholic potassium hydroxide solution to 3-R-phenyl-5-alkoxy-1,2,4-triazoles. The dissociative ionization of 3-R-phenyl-5-alkoxy-1,2,4-triazoles and 3-R-phenyl-1,2,4-triazolin-5-ones has been examined. The mass spectra of the oxadiazoles have been compared with those of the triazoles.Translated from Khimiya Geterotslklicheskikh Soedinenii, No. 11, pp. 1553–1556, November, 1986.     

Reactions of 3-amino-1,2,4-triazoles with cinnamic aldehydes

The reaction of 3-amino- and 3-amino-5-methylthio-1,2,4-triazoles with cinnamaldehyde takes two directions to form mixtures of 5-[N-(3-phenylpropenylideneamino)]-1H-1,2,4-triazoles and 5-phenyl-4,5,6,7-tetrahydro[1,2,4]triazolo[1,5-a]pyrimidin-7-ols.