No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Chemical reactivity of 3-hydrazino-5,6-diphenyl-1,2,4-triazine towards pi-acceptors activated carbonitriles
Abstract
Behaviour of 3-hydrazino-5,6-diphenyl-1,2,4-triazine 1 as electron donor towards different electron acceptors activated carbonitriles has been investigated and a novel fused heterocyclic system and 2,3-disubstituted 1,2,4-triazines have been obtained. Compound 1 reacts with 1,2-dicyanobenzene as pi-acceptor in DMF to form benzencarboximidamide 16, while reaction of 1 with alpha-bromomalononitrile 17 in boiling DMF affords compound 18. On the other hand, compound 1 reacts with tetracyanoethane 23 in DMF to yield compound 24. The route of reaction in DMF indicates that charge-transfer cornplexation is the key intermediate to obtain new heterocyclic systems. Structures of the products are established by MS, 1R, UV-Vis, CHN and H-1 NMR spectral data.
... [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Moreover, synthesis and chemistry of polyfunctional 1,2,4-triazines have been proved to be very useful in the chemotherapeutic chemistry, biochemistry and pharmacological chemistry, and in plant protection (cellobiase and amylolytic agents). [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Abdel-Rahman et al. [18][19][20][21][22][23] have studied the chemical reactivity of uncondensed 1,2,4-triazine bearing a hydrazino group toward sulfur, oxygen, nitrogen, and halogen compounds in various media. Recently, noted that most of the reactions of activated nitriles with amino and/or hydrazino-groups led to the direct formation of fused heterobicyclic nitrogen systems. ...
... [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Moreover, synthesis and chemistry of polyfunctional 1,2,4-triazines have been proved to be very useful in the chemotherapeutic chemistry, biochemistry and pharmacological chemistry, and in plant protection (cellobiase and amylolytic agents). [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Abdel-Rahman et al. [18][19][20][21][22][23] have studied the chemical reactivity of uncondensed 1,2,4-triazine bearing a hydrazino group toward sulfur, oxygen, nitrogen, and halogen compounds in various media. Recently, noted that most of the reactions of activated nitriles with amino and/or hydrazino-groups led to the direct formation of fused heterobicyclic nitrogen systems. ...
... Cyclocondensation of benzil with diaminoguanidine in refluxing n-butanol produced the 3-hydrazino-5,6-diphenyl-1,2,4-triazine (1). [18] The interaction between compound 1 and chloroacetonitrile in refluxing N,N-dimethylformamide (DMF), yielded the 4-amino-7,8-diphenyl-1,2,4triazino [4,3-b] [1,2,4]triazine (2) [Scheme 1]. ...
The interaction between 3-hydrazino-5,6-diphenyl-1,2,4-triazine (1) and chloroacetonitrile has produced 4-amino-7,8-diphenyl-1,2,4-triazino[4,3-b][1,2,4]triazine (2). The chemical reactivity of compound 2 was investigated by acylation, aroylation, thioacylation, and reaction with triphenylphosphine and diethyl hydrogen phosphite. Furthermore, compound 2 was reacted with cyanamide followed by ring closure reaction with malonic acid to produce the N-(1-(7,8-diphenyl-2H[1,2,4]triazino[4,3-b] [1,2,4]triazin-4-yl)-4,6-dioxo-1,4,5,6-tetrahydropyrimidin-2-yl)acetamide (11). The structures of new compounds were deduced from their elemental analysis and spectral measurements (Fourier-transform infrared, 1 H nuclear magnetic resonance [NMR], 13 C NMR, 31 P NMR, and mass spectra). Compounds 2-8 were screened for anti-mycobacterial activity and the compounds 5, 4, and 8 exhibited moderate activity while others poorly.
... o-Diamines as hydrazino moiety are very active substrates for the building of various heterobicyclic nitrogen systems 9,10 . Abdel-Rahman et al. 11 , have been investigated the behavior of hydrazino-groups towards various bi-electrophilic compounds. Based on these observations, and as a part of our continuing work in these areas 12,13 , the present work describes other attempts for the behavior of 3-hydrazino-1,2,4triazinone towards some activated electrophilic compounds in different medium and conditions in view of their bactericidal effects. ...
... All reactions were monitored by TLC, using silica gel coated Al plates with fluorescent indicator F254. 4-Nitrobenzoyl isothiocyanate was obtained from refluxing 4-nitrobenzoyl chloride with ammonium thiocyanate in dry acetone 11 , and 6-(2-aminophenyl)-3-thioxo-1,2,4-triazin-5(4H)one (1) also obtained from refluxing isatin with thiosemicarbazide in aq. NaOH 14 , according to the reported methods. ...
... Formation of compound 8 Formation of compound 9 from 3Abdel-Rahman et al.11 studied the reactivity of strong nucleophile reagents towards active carbonitriles as electrophile reagents. Similarly, treatment of 3-hydrazino-1,2,4-triazinone 3 with benzoyl carbonitrile in ethanol with drops of piperidine, yielded N-(2-(4-imino-8-oxo-3-phenyl-1,8-dihydro-4H-[1,2,4]triazino[4,3-b][1,2,4]triazin-7yl)phenyl)pivalamide (10) Scheme 5. Scheme 5. Synthesis of compound 10 from 3 Former structures of new compounds obtained were deduced from their elemental analysis and spectral measurements. ...
p class="Mabstract">The behavior of 3-hydrazino-6-aryl-1,2,4-triazin-5-one towards the active electrophilic compounds in polar and/ or non-polar solvents and various times and temperatures, has been studied. N -[2-(3-(3/5-(4-Nitrophenyl)-5/3-thioxo-1 H -1,2,4-triazol-1-yl)-5-oxo-1,2,4-triazin-6-yl)phenyl]pivalamides were obtained from the reaction of N -(2-(3-hydrazineyl-5-oxo-1,2,4-triazin-6-yl)phenyl)-pivalamide with 4-nitrobenzoyl isothiocyanate in THF and/ or EtOH-piperidine respectively. Also, N -(2-(3-hydrazineyl-5-oxo-1,2,4-triazin-6-yl)phenyl)-pivalamide was shown a strong nucleophilic behavior by reaction with N -phenyl-thiourea to produce N -[2-(5-oxo-3-(2-(phenylcarbamothioyl)-hydrazineyl)-1,2,4-triazin-6-yl)phenyl]pivalamide, which upon cyclization with diethyl carbonate produced N -(2-(5-oxo-3-(5-oxo-4-phenyl-3-thioxo-1,2,4-triazolidin-1-yl)- 1,2,4-triazin-6-yl)phenyl)pivalamide. Moreover, N -(2-(3-hydrazineyl-5-oxo-1,2,4-triazin-6-yl)phenyl)pivalamide studied its behavior by reaction with cyanoacetic acid, chloroacetonitrile, and/ or benzoyl carbonitrile to produce N -(2-(3-amino-4,8-dioxo-4 H -[1,2,4]triazino[4,3- b ][1,2,4]triazin-7-yl)phenyl)pivalamide, N -(2-(4-amino-8-oxo-2 H -[1,2,4]triazino[4,3- b ][1,2,4]triazin-7-yl)phenyl)pivalamide and N -(2-(4-imino-8-oxo-3-phenyl-4 H -[1,2,4] triazino [4,3- b ][1,2,4]triazin-7-yl)phenyl)pivalamide. Structure of the products was established upon their elemental analysis and FT-IR, <sup>1</sup>H/ <sup>13</sup>C NMR, and MS. The new compounds were evaluated as antibacterial agents some Gram-positive and negative bacteria. Some compounds were showed the highest inhibition activity towards Pseudomonas aeruginosa , Bacillus subtilis , Bacillus cereus , and Sarcina lutea bacteria and lowest inhibitory activity against Escherichia coli bacteria. </p
... In addition, introduction fluorine atoms to pyrazolopyrimidine enhance and improve their pharmacological properties [8] [9]. Abdel Rahman et al. [10] [11] [12], reported that the orientation of cyclization reactions of functionalized amino and/or hydrazine bearing heterocyclic moieties depends on the effect of substituents, solvent pH, temper- ...
... Found: C, 63.41%; H, 3.29%; Cl, 6.25%; F, 3.31%; N, 22.89%.1-(1'-phenyl-3'-methyl-4'-(4"-fluorophenyl)-pyrazolo[3,4-d] pyrimidine-6'-yl)-2-imino-4-amino-6-(4'-chlorophenyl)-pyrimidine-5-carboxylic acid(11).A mixture of 4 (0.01 mol) and 10 (0.01 mol) in EtOH (100 ml) with drops of piperidine refluxed for 6 h, cooled then poured onto ice. The solid produced filtered off and crystalized from dioxane to give 11 as deep brown crystals.Yield 60%, m.p. 198˚C -200˚C. ...
... Interestingly, diimino derivative 363 was obtained upon condensation with two equivalents of cycanoacetic acid (entry 3). 136 Thermal cyclocondensation of hydrazine 360 with triethyl orthoformate afforded triazolotriazine 365 (entry 4). 137 Hydrazides 366 (easily prepared via EDCI-mediated coupling of hydrazine 360 with 2-arylacetic acids) could cyclize to triazolotriazines 367 under heating in acetic acid in moderate to excellent yields (entry 5). ...
... In addition, 13 C NMR spectra of compounds 3-6 revealed signals at δ 170-160, 146-145 and 142-140 ppm, corresponding to the presence of C=O, C-F, C=N; δ 130-122 ppm, corresponding to aromatic carbons; and δ 70 ppm, corresponding to aliphatic carbons. Abdel-Monem et al. reported the behavior of 3-amino-1,2,4-triazines toward the π-electron acceptor of unsaturated aroyl isothiocyanate in solvents with different polarities and isolated the isomeric structures [24,25]. Similarly, the interaction between compound 3 and aroyl isothiocyanate 7 (obtained by refluxing aroyl chloride with ammonium thiocyanate in dry acetone) [25] in a non-polar solvent such as dioxane and a polar solvent such as ethanol in a few drops of piperidine afforded an isomeric structure of N- (2-(4-(3,5- Three singlets at δ ~8.7-9.5 ppm were observed in the 1 H NMR spectra of compounds 8 and 9 (s, 3H, CH aromatic nitro). ...
New fluorine-substituted polyfunctional pyrimido-[1,2-b]-[1,2,4]triazines and [1,3,5]-triazino[1,2-b]-[1,2,4]triazines were synthesized via the reaction between 3-amino-6-(2-aminophenyl)-1,2,4-triazin-5(2H)-one with polyfunctional oxygen/sulfur/nitrogen reagents under different conditions. Structures of the target compounds were deduced by elemental analysis and spectral measurements (IR, 1H/13C NMR, and mass spectra). According to the obtained inhibitor assay results, the inhibition activity of the new fluorine-substituted 1,2,4-triazines toward CDK2 decreased in the order of compounds 3 > 8 > 9 > 6 > 13 > 15.
... were synthesized from refluxing 5-hydrazine-4-amino-1,2,4-triazole (9) with triethylortho-formate (TEA/THF) and /or with CS 2 (in DMF) (Scheme 2). Formation of compound 14 may be concluded to be firstly by synthesized via esterification of 9 and secondly by elimination of one mole of ethanol, while formation of 13 via addition to S=C=S followed by elimination of H 2 S [25] . Structures of 13 and 14 were deduced from their elemental and spectral analysis thus the FT-IR spectrum of 14 showed the characteristic stretching vibration absorption bands (cm -1 ) at 3249 (NH), 1624(CONH), while compound 13 showed at (cm -1 ) 3269 (NH), 2402 (SH) and 1634 (CONH), in addition to (cm -1 ) 1602, 1308, which is related to C=N, NCSN. 1 HNMR spectrum of 13 showed signals at δ 2.5(s, br., 1H, NH of tetrazine), 14.21 ppm (s, 1H, NH of tetrazine), and δ 5.8 of SH proton. ...
Abstract: Novel 8-(4-fluorophenyl)-6,6-diphenyl-3-(pyrimidin-4-yl) -5,6,7,8-tetrahydro-6l5-
[1,2,4]triazolo [4,3-a][1,3,5]diazaphosphinin-6-ol(5),8-(4-fluorophenyl)-6-phenyl-3-(pyrimidin-4-yl)-7,8-
dihydro [1,2,4]triazolo [4,3-b][1,2,4]triazine (6), 8-(4-fluorophenyl)-6-methyl-3-(pyrimidin-4-yl)-
[1,2,4]triazolo[4,3-b][1,2,4]triazin-7(8H)-one (7) and 8-(4-fluorophenyl)-3-(pyrimidin-4-yl)-
[1,2,4]triazolo[4,3-b][1,2,4]triazine-6,7(5H,8H)-dione (8) and 7-(pyrimidin-4-yl)-3,4-dihydro-
[1,2,4]triazolo[4,e][1,2,4,5,3]tetrazaphosphinine (10), 3-(pyrimidin-4-yl)-1,7-dihydro-[1,2,4]triazolo[4,3-
b][1,2,4,5]tetrazine (11), 6-(2-chloro-6-fluorophenyl)-3-(pyrimidin-4-yl)-1,5,6,7,8,8a-hexahydro-
[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine (12), 3-(pyrimidin-4-yl)-1,7,8,8a-tetrahydro-[1,2,4]triazolo[4,3-
b][1,2,4,5]tetrazine-6(5H)-thione (13) and 3-(pyrimidin-4-yl)-1,7,8,8a-tetrahydro-[1,2,4]triazolo[4,3-
b][1,2,4,5]tetrazin-6(5H)-one (14) have been synthesized via heterocyclization of 3-(pyridin-4yl)-4-
amino-5-substituted amino-1,2,4-triazole (3) and 3-(pyridin-4yl)-4-amino-5-hydrazino-1,2,4-triazole (9)
with α,β-bifunctional reagents such as chloromethyldiphenyl-phosphanoxide, phenacyl bromide, pyruvic
acid, diethyl oxalate, triethylphosphite, triethyl orthoformate, fluorinated benzaldehydes, ethyl
chloroformate and carbon disulfide in different experimental conditions. The molecular structures of the
synthesized target molecules were elucidated by FT-IR, 1H NMR, 13C NMR and mass spectral data, in
addition to the fine elements analysis C.H.N.% data. The antimicrobial and anti-inflammatory effects of
the obtained derivatives were evaluated and compared with that of the standard Indomethacin, Nalidixic
acid and Nystatin.
... Recently, the most reactions of activated nitrites take place in basic medium leading to novel heterocyclic systems [29] [30]. Similarly, amino-pyrazolyl-1,2,4-triazinano derivatives 4-7 were obtained from the interaction between compound 3 and arylidenecyanoacetic acid (EtOH-piperidine), acetyl acetanilide (DMF), ethyl cyanoacetate (TFH) and/or malono nitrile (EtOH-piperidine) (Scheme 2). ...
... Hydrazino groups are used as starting materials for bioactive isolated heterobicyclic systems [24][25][26]. Refluxing 3a with hydrazine hydrate in ethanol produced 4-aryl-2,5,7-tri(hydrazinopyrimido [4,5-d]pyrimidine (13) Ring closure reactions of 13 with malononitrile in boiling ethanol with a few drops of piperidine as a catalyst via cycloaddition led to the direct formation of 8-(4'-fluorophenyl)-2,5,7-tri(3',5'-diaminopyrazol-l'-yl) pyrimido [4,5-d]pyrimidine 14 (Scheme 3). ...
... Some pyrimidines exhibit anti-inflammatory [9][10][11][12], analgetic [12,13], antimicrobial [14], antiviral [15], antimalarial [16], antidepressant [17], or anticancer activity [18][19][20][21][22][23]. In contrast, 1,2,4-triazines have proven to be useful in synthetic chemistry, particularly in various one-step heterocyclization reactions that proceed via the insertion of two carbon atoms bearing bifunctional groups [24][25][26]. The structural diversity and biological significance of 1,2,4-triazines have received considerable interest due to their wide range of applications [27][28][29][30][31]. ...
A Knoevenagel one-pot synthesis of 6-amino-4-oxo-8-(2-thienyl)-3-[2-(2-thienyl)vinyl]-4H-pyrimido[2,1- c][1,2,4]triazine-7-carbonitrile 2 via the reaction of 3-amino-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-5(4H)-one 1 with thiophene- 2-carbaldehyde and malononitrile under basic conditions is described. New fused heterotricyclic nitrogen systems, such as pyrimido[5',4':5,6]pyrimido[2,1-c][1,2,4]triazine 5, 7, 9, 12, 13, 20 and pyrido[3',2':5,6]pyrimido[2,1- c][1,2,4]triazine 10, 11, 14 were achieved by treating 2 with cyanamide, urea, thiourea, and CS2 in ethanolic ethoxide, formamide, triethyl orthoformate and then ammonia, malononitrile, ethyl cyanoacetate, chloroacetyl chloride and phenyl isothiocyanate. The structures of the products have been deduced from their elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR). The antimicrobial activity of all synthesized compounds was screened.
... Some pyrimidines exhibit anti-inflammatory [9][10][11][12], analgetic [12,13], antimicrobial [14], antiviral [15], antimalarial [16], antidepressant [17], or anticancer activity [18][19][20][21][22][23]. In contrast, 1,2,4-triazines have proven to be useful in synthetic chemistry, particularly in various one-step heterocyclization reactions that proceed via the insertion of two carbon atoms bearing bifunctional groups [24][25][26]. The structural diversity and biological significance of 1,2,4-triazines have received considerable interest due to their wide range of applications [27][28][29][30][31]. ...
A Knoevenagel one-pot synthesis of 6-amino-4-oxo-8-(2-thienyl)-3-[2-(2-thienyl)vinyl]-4H-pyrimido[2,1-c][1,2,4]triazine-7-carbonitrile 2 via the reaction of 3-amino-6-[2-(2-thienyl)vinyl]-1,2,4-triazin-5(4H)-one 1 with thio-phene-2-carbaldehyde and malononitrile under basic conditions is described. New fused heterotricyclic nitrogen systems, such as pyrimido[5',4':5,6]pyrimido[2,1-c][1,2,4]triazine 5, 7, 9, 12, 13, 20 and pyrido[3',2':5,6]pyrimido[2,1-c][1,2,4]triazine 10, 11, 14 were achieved by treating 2 with cyanamide, urea, thiourea, and CS2 in ethanolic ethoxide, formamide, triethyl orthoformate and then ammonia, malononitrile, ethyl cyanoacetate, chloroacetyl chloride and phenyl isothiocyanate. The structures of the products have been deduced from their elemental analysis and spectral data (IR, 1 H-NMR, 13 C-NMR). The antimi-crobial activity of all synthesized compounds was screened.
3-Amino-1,2,4-triazines are considered versatile compounds for its significance as building blocks in synthetic and pharmaceutical chemistry. The synthesis, chemical reactivity, and applications of substituted 1,2,4-triazines bearing an amino group were described in this review. The presence of the amino group at position 3 exhibited unique reactivities towards carbonitrile, carbonyl and isothiocyanate reagents. The reactions were divided into several categories, depending on the other substituents on the 1,2,4-triazine ring. In this review, relevant and appropriate applications of the synthesized, isolated, and condensed heterocycles derivatives were reported.
The tautomerization reactions of the 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one studied by means of M06-2x and CBS-QB3 theoretical methods. The measured energy profiles are complemented with kinetic rate coefficients calculations using transition state theory (TST). In line with the optimized tautomers geometries using the CBS-QB3 method, the natural bond orbital (NBO) analysis reveals that the stabilization energies of non-bonding LP(e)S8 to the σ*N2–C3 antibonding orbitals increase from tautomers 1 to 2. Furthermore, the delocalization energies of LP(e)S8→σ*N2–C3 could explain the increase of LP(e)S8 non-bonding orbitals occupancies in the tautomers 1 and 2 (2 > 1). The increase of LP(e)S8→σ*N2–C3 delocalizations could fairly explicate the kinetics of tautomeric pathways 1 and 2 (k2 > k1). Moreover, the HOMO–LUMO energy gap is increased parallel with the decreasing of activation energy barriers. NBO results also show that the kinetics of these processes controlled using LP→σ* resonance energies. Furthermore, nucleus-independent chemical shift (NICS) indices show the calculated reaction and energy barriers are involved by changes in aromaticity characters as well as electron transfer from LP(e)S8 to σ*N2–C3 orbitals, thus these reactions are controlled from both thermodynamic and kinetic viewpoints by the changes aromaticity characters.
Behaviour of 3-hydrazino-5,6-diphenyl-1,2,4-triazine 1 as electron donor towards different electron acceptors activated carbonitriles has been investigated and a novel fused heterocyclic system and 2,3-disubstituted 1,2,4-triazines have been obtained. Compound 1 reacts with 1,2-dicyanobenzene as π-acceptor in DMF to form benzencarboximidamide 16, while reaction of 1 with a-bromomalononitrile 17 in boiling DMF affords compound 18. On the other hand, compound 1 reacts with tetracyanoethane 23 in DMF to yield compound 24. The route of reaction in DMF indicates that charge-transfer complexation is the key intermediate to obtain new heterocyclic systems. Structures of the products are established by MS, IR, UV-Vis, CHN and 1H NMR spectral data.
Benzil reacts with diaminoguanidine nitrate to yield the nitrate salt of benzil mono[(aminoamidino)hydrazone](2). The hydrazone (2) is unstable, and cyclises on melting or in solvents to 5,6-diphenyl-3-hydrazino-1,2,4-triazine (3). Diazotisation of the hydrazone (2) and of hydrazine (3) affords the same product, 6,7-diphenyltetrazolo-[1,5-b]-as-triazine (9) which decomposes in boiling secondary amines to yield substituted 3-amino-5,6-diphenyl-1,2,4-triazines and hydrazoic acid. Both the hydrazone (2) and the hydrazine (3) react with triethyl orthoformate or formic acid to give 6,7-diphenyltriazolo[4,3-b]-as-triazine (16), which was also prepared, unambiguously, from benzil and 3,4-diamino-1,2,4-triazole. Although conditions favourable for Dimroth rearrangement were employed, no such transformations were encountered in the reactions of the bicyclic systems (9) and (16).
Studies on the chemical constituents of sulfur containing the 5-oxo-1,2,4-triazin-3-yl moiety are reviewed. The synthesis. unique features of the structures and biological significance of these constituents are discussed.