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.     

3,3]-Sigmatropic shifts and retro-ene rearrangements in cyanates, isocyanates, thiocyanates, and isothiocyanates of the form RX-YCN and RX-NCY

Retro-ene type [2π + 2π + 2σ] and [3,3]-sigmatropic shift reactions involving the substituent groups R in heteroatom-substituted cyanates and thiocyanates RX-YCN and the isomeric isocyanates and isothiocyanates of the type RX-NCY (X = CR(2), NR', O, or S; Y = O or S) have been investigated computationally at the B3LYP/6-311++G(d,p) level. Retro-ene reactions of alkyl derivatives of the title compounds afford alkenes, imines, carbonyl and thiocarbonyl compounds together with HNCO (HNCS) or HOCN (HSCN). [3,3]-Sigmatropic shifts (hetero-Cope rearrangements) of the corresponding allyl, propargyl, benzyl, and aryl derivatives causes allylic rearrangements, propargyl-allenyl rearrangement, conversion of benzyl cyanates to o-isocyanatotoluenes, and conversion of N-cyanatoarylamines to o-isocyanatoanilines, etc. The corresponding rearrangements of allyl thiocyanates, arylamino thiocyanates and isothiocyanates, and arylsulfenyl thiocyanates and isothiocyanates are also described.     

Bond-switch rearrangement of 3-oxo-Δ4-1,2,4-thiadiazolin-5-yl ureas

5-Amino-3-oxo-Δ⁴-1,2,4-thiadiazolines 5a,b react with isocyanates to yield 1,2,4-thiadiazolidine derivatives 9a-d via bond switching of the corresponding isomers 7 . The same type of products 9e-m was obtained by treatment of 5-amino-1,2,3,4-thiatriazoles 6a-d with two equivalents of isocyanate.     

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. I. The reaction of N-cyanocarbonimidodithioic acid diesters with hydrazines

The reaction of N-cyanocarbonimidodithioic acid di(alkyl and aralkyl)esters with different alkyl-, aralkyl- and arylhydrazines to yield 1-substituted-3-R-thio-5-amino-1H-1,2,4-triazoles ( 3 ) and 2-substituted-3-R-thio-5-amino-2H-1,2,4-triazoles ( 4 ) was studied. Isolation of the different types of isomeric pairs of 3 and 4 helped to prove the structure of products obtained which made possible correction of some confusion in the literature. The 3 (R = H) tautomeric structure of the non-substituted derivatives was supported by comparison of their uv and cmr spectra with those of the alkylated and aralkylated derivatives 3 and 4 , respectively, again correcting confusion in the literature. An hplc determination of the ratio of products 3 and 4 formed in the above reactions with different hydrazines made it possible to prove the mechanism of the reaction.     

On triazoles XLI [1]. Synthesis of meso‐ionic [1,2,4]triazolo[5,1‐c]thiadiazoles

Type 6 meso‐ionic [1,2,4]triazolo[5,1‐c]thiadiazoles were synthesised by oxidation of the corresponding N‐methyl‐N'‐(substitutedbenzal)‐5‐amino‐3‐substituted‐1,2,4‐triazol‐1‐yl)thiohydrazide ( 3 ) type bases or their [1,2,4]triazolo[5,1‐d][1,2,3,6]tetrazepin‐5‐thion ( 4 ) type ring tautomers. Besides spectroscopical evidence a preparative proof of their structure was also provided. X‐ray diffraction analysis of 3‐methylthio‐6‐morpholino‐1,2,4‐triazolo[5,1‐c]thiadiazole ( 8 ) showed quite unusual bond lengths for the N¹‐S and S‐C³ bonds of the thiadiazole ring proving the meso‐ionic character of these derivatives unequivocally.     

Notiz über die Reaktion von Methylhydrazin mit N-Cyano-azomethinen. Abhängigkeit des Reaktionsverlaufs von der Natur der Abgangsgruppe

The reaction of methylhydrazine with N-cyanoazomethines 1 containing a thioalkyl leaving group yields the 3-amino-1,2,4-triazole derivatives 2 , whereas the N-cyanoazomethines 1 containing an alkoxy leaving group give the isomeric 5-amino-1,2,4-triazoles 3. The yields are excellent and the position selectivity is high. The structures of the 1,2,4-triazole derivatives were determined with the aid of proton-coupled ¹³C-NMR. spectra.     

On triazoles. XXXIX. Synthesis and structure of some 1,2,4-triazolo[1,5-a]pyrimidin-5-one oximes

Some 1,2,4-triazolo[1,5-a]pyrimidin-5-one derivatives 1 and their alicyclic condensed ring analogues 2-3 were converted through the corresponding “imino chlorides” 4-6 to the oximes 7-9 . The “E” isomeric structure of the products obtained was proven with the use of cmr using the spectral data of the corresponding “benzyloximino” derivatives 10-12 prepared as model compounds.     

13C n.m.r. spectroscopy of diethyl alkyl- and benzyl-phosphonates. A study of phosphorus–carbon spin–spin coupling constants over one to seven bonds

¹³C chemical shifts and ³¹P? ¹³C spin–spin coupling constants are reported for 10 alkyl-, 20 benzyl- and 3 (naphthylmethyl)-phosphonates. While in saturated aliphatic chains P–C couplings over more than four bonds cannot be resolved, couplings over up to seven bonds are observed in the benzyl type systems. Conformational and substituent effects on J(PC) are studied and discussed. ⁿJ(PF) (n = 4, 5, 6) are reported for the isomeric (fluorobenzyl)phosphonates and ⁿJ(PP) (n = 5, 6, 7) were obtained from the ¹³C satellites in the ³¹P n.m.r. spectra of the isomeric diphosphonates, C₆H₄[CH₂P(O)(OEt)₂]₂. Comparison of those ¹³C absorptions of the latter, which represent the X parts of ABX or AA′X spin systems, with the spectra of the corresponding (methylbenzyl)phosphonates, CH₃C₆H₄CH₂P(O)(OEt)₂, yielded the relative signs of ⁿJ(PC) (n = 2–6).     

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 XLV [1]. synthesis of 5,7‐diamino‐1,2,4‐triazolo[1,5‐a] [1,3,5]triazines

Dedicated to Professor András Messmer on the occasion of his 80^th birthday The reaction of differently substituted 5‐amino‐1,2,4‐triazoles ( 5 ) with isothiourea derivatives ( 3 ) to yield isomeric 5,7‐diamino‐1,2,4‐triazolo[1,5‐a][1,3,5]triazines ( 6 and 7 ), previously described as not proceeding in melt, was performed in different solvents as well as in the melt at 150‐160°. It was proved that the above reaction had rather general validity. The structure of isomers 6 and 7 were proved spectroscopically. The structure of 6/5 (Q = ethylamino) was corroborated with single crystal X‐ray diffraction determination, as well.     

On triazoles XLIII. Synthesis of 1,2,4‐triazolyl isoquinolinium zwitter ions

Type 8 isoquinolinium zwitter ions were synthesised by the reaction of type 1 diketones or type 2 pyrylium salts with different 5‐amino‐3‐Q‐1H‐1,2,4‐triazoles. Spectroscopic and X‐ray diffraction evidence was given for the zwitter ion structure of the products obtained. The position of the negative charge on the 1,2,4‐tiazolium ring was proved by comparison of the cmr and uv spectra of the products obtained with the three possible N‐benzyl derivatives 14–16 prepared for this purpose.     

On triazoles. XXI. Synthesis of 1,2,4-triazolyldithiocarbonates

The reaction of 5-amino-1,2,4-triazoles 1 with carbon disulfide and alkylating agents in basic condition to yield alkyl, aralkyl and aryl (5-amino-3-Q-1,2,4-triazol-1-yl)dithiocarbonates 2 and alkyl (3-Q-1,2,4-triazol-5-yl-amino)dithiocarbonates 3 was studied. The isomeric and tautomeric structure of derivatives obtained was proved with the help of their uv, pmr and cmr spectra using model compounds prepared for this purpose. The results obtained enabled us to correct some confusion in the literature.     

Novel stannatranes of the type N(CH2CMe2O)3SnX (X = OR, SR, OC(O)R, SP(S)Ph2, halogen). Synthesis, molecular structures, and electrochemical properties

The syntheses of the stannatrane derivatives of the type N(CH(2)CMe(2)O)(3)SnX (1, X = Ot-Bu; 2, X = Oi-Pr; 3, X = 2,6-Me(2)C(6)H(3)O; 4, X = p-t-BuC(6)H(4)O; 5, X = p-NO(2)C(6)H(4)O; 6, X = p-FC(6)H(4)O; 7, X = p-PPh(2)C(6)H(4)O; 8, X = p-MeC(6)H(4)S; 9, X = o-NH(2)C(6)H(4)O; 10, X = OCPh(2)CH(2)NMe(2); 11, X = Ph(2)P(S)S; 12, X = p-t-BuC(6)H(4)C(O)O; 13, X = Cl; 14, X = Br; 15, X = I; 16, X = p-N(CH(2)CMe(2)O)(3)SnOSiMe(2)C(6)H(4)SiMe(2)O) are reported. The compounds are characterized by X-ray diffraction analyses (3-8, 11-16), multinuclear NMR spectroscopy, (13)C CP MAS (14) and (119)Sn CP MAS NMR (13, 14) spectroscopy, mass spectrometry and osmometric molecular weight determination (13). Electrochemical measurements show that anodic oxidation of the stannatranes 4 and 8 occurs via electrochemically reversible electron transfer resulting in the corresponding cation radicals. The latter were detected by cyclic voltammetry (CV) and real-time electron paramagnetic resonance spectroscopy (EPR). DFT calculations were performed to compare the stannatranes 4, 8, and 13 with the corresponding cation radicals 4(+?), 8(+?), and 13(+?), respectively.     

The Synthesis of 3,5-Diamino-1,2,4-oxadiazoles. 1st Communication

Reaction of the 1-substituted-3-cyano-isothioureas 6 with hydroxylamine gave mixtures of the 5-amino-3-substituted-amino-1,2,4-oxadiazoles 1 and the isomeric 3-amino-5-substituted-amino-1,2,4-oxadiazoles 8 in which 1 usually predominated. The structural assignment of these products is discussed. In a second method, the 2-hydroxy-1-methyl-1-phenyl-guanidine 15 was converted to the corresponding 3-disubstituted-amino-5-trichloromethyl-1,2,4-oxadiazole 16 , a precursor to the 5-amino derivatives 17 by nucleophilic displacement of the trichloromethyl group.     

On triazoles XVIII. . an unexpected rearrangement observed during the reaction of 5-amino-1,2,4-triazoles with N-heterocyclic β-oxo-esters

In the course of the synthesis of pyrido[4,3-d]-1,2,4-triazolo[1,5-a]pyrimidine derivatives 3c representing a novel ring system an unexpected rearrangement of the intermediate enamines to yield 5 was observed. A mechanism of the formation of 5 was suggested. The isomeric pyrido[4,3-e]-1,2,4-triazolo[1,5-a]pyrimidine derivatives 4c containing also a new ring system were obtained, too. The structure of products obtained was proved with the help of their uv, cmr and X-ray spectra.     

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.     

On triazoles. XXVIII . Synthesis of isomeric 1,2,4-triazolylcarbothiohydrazides

Different 3a , 3b , 9 , 10 and 12 type 5-amino-1,2,4-triazolylcarbothiohydrazide isomers representing all possible isomeric types derived from 5-amino-1,2,4-triazoles were synthesised from the corresponding 5-amino-1,2,4-triazolyldithiocarbonates and hydrazines. HPLC measurements proved that in case of mono-substituted hydrazines the steric press in the intermediate 6 caused besides formation of the expected derivative 3a the formation of compounds 4 and 5 , too, while the intermediate 7 yielded only 3b . Thermal rearrangement of derivatives 3a in acetic acid led to isomers 9 and 10 , respectively.     

Heterocyclization of Functionalized Heterocumulenes with C,N- and C,O-Binucleophiles. 1. Cyclocondensation of 1-Chloroalkylheterocumulenes and N-(1-Chloroalkylidene)urethanes with 2-Cyanomethylpyridine

The interaction of 1-chloroalkyl isocyanates, 1-chloroalkylcarbodiimides, 1,1-dichloroalkyl isocyanates, and N-(1-chloroethylidene)-O-methylurethanes with 2-cyanomethylpyridine has been investigated. An effect of organic base has been detected on the regioselectivity of the cyclocondensation of 1-chloroalkyl isocyanates, which leads to 2,3-dihydro-1H-pyrido[1,2-c]pyrimidin-1-one or the isomeric 2,3-dihydro-1H-pyrido[1,2-c]pyrimidin-3-one. Irrespective of the cyclization conditions 1-chloroalkylcarbodiimides react with the formation of 1-imino-2,3-dihydro-1H-pyrido[1,2-c]pyrimidines. One type of product, a 1H-pyrido[1,2-c]pyrimidin-1-one, was also isolated from 1,1-dichloroalkyl isocyanates and N-(1-chloroalkylidene)urethanes.     

Reversed steric order of reactivity for tert-butyl and adamantyl-3-cyanomethylene-1,2,4-triazines

Reactions of 2-(6-tert-butyl-5-oxo-4,5-dihydro-1,2,4-triazin-3(2H)-ylidene)-3-oxo-3-R-propanenitriles (R = t-Bu, Ad-1) with tert-butyl bromoacetate gave the corresponding N(2), C(5)O bis-alkylation products. Treatment of the latter with t-BuLi, in the case of R = t-Bu, led to intramolecular condensation at the exocyclic nitrile group. However, in the case of R = Ad-1, the condensation with the sterically more hindered carbonyl group was observed to give diastereomerically pure 8-cyanopyrrolo[1,2-b][1,2,4]triazine-6-carboxylate derivatives. The structures of the isolated products were confirmed by spectral methods and X-ray single-crystal diffraction.