A study on the condensation reaction of aryl substituted 4-amine-1,2,4-triazole with benzaldehydes: Structures and spectroscopic properties of schiff bases and stable hemiaminals

Article abstract of DOI:10.1016/j.molstruc.2016.02.047

A series of stable hemiaminals and Schiff bases containing 3,5-disubstituted 1,2,4-triazole derivatives were synthesized. The structure of the prepared compounds was confirmed by means of ¹H NMR, ¹³C NMR, IR, MS and elemental analysi

Full text of DOI:10.1016/j.molstruc.2016.02.047

Accepted Manuscript
A study on the condensation reaction of aryl substituted 4-amine-1,2,4-triazole with
benzaldehydes: Structures and spectroscopic properties of schiff bases and stable
hemiaminals
Katarzyna Wajda-Hermanowicz, Damian Pieniążczak, Robert Wróbel, Aleksandra
Zatajska, Zbigniew Ciunik, Sławomir Berski
PII:
S0022-2860(16)30140-5
10.1016/j.molstruc.2016.02.047
MOLSTR 22256
DOI:
Reference:
To appear in: Journal of Molecular Structure
Received Date: 24 September 2015
Revised Date: 11 February 2016
Accepted Date: 11 February 2016
Please cite this article as: K. Wajda-Hermanowicz, D. Pieniążczak, R. Wróbel, A. Zatajska, Z. Ciunik,
S. Berski, A study on the condensation reaction of aryl substituted 4-amine-1,2,4-triazole with
benzaldehydes: Structures and spectroscopic properties of schiff bases and stable hemiaminals, Journal
of Molecular Structure (2016), doi: 10.1016/j.molstruc.2016.02.047.
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ACCEPTED MANUSCRIPT

A Study on the Condensation Reaction of Aryl
ACCEPTED MANUSCRIPT
Substituted 4-Amine-1,2,4-triazole with
Benzaldehydes: Structures and Spectroscopic
Properties of Schiff Bases and Stable Hemiaminals.
Katarzyna Wajda-Hermanowicz*, Damian Pieniążczak, Robert
Wróbel, Aleksandra Zatajska, Zbigniew Ciunik, Sławomir Berski
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, Wrocław 50-383,
Poland
E-Mails: alecempire@o2.pl (D.P.), robert.wrobel@chem.uni.wroc.pl
(R.W.), aleksandra.zatajska@chem.uni.wroc.pl (A.Z.), ciunik@wchuwr.pl
(Z.C.), slawomir.berski@chem.uni.wroc.pl (SB).
* Author to whom correspondence should be addressed; E-Mail:
katarzyna.wajda-hermanowicz@chem.uni.wroc.pl,
Abstract
A series of stable hemiaminals and Schiff bases containing 3,5-disubstituted 1,2,4-
triazole derivatives were synthesized. The structure of the prepared compounds was
1
13
confirmed by means of H NMR, C NMR, IR, MS and elemental analysis. The steric
and electronic effects of the triazole ring substituents on the hemiaminal formation was
also discussed. Single crystal X-ray diffraction studies of hemiaminals obtained from 4-
amino-3,5-dipyridyn-2-yl-1,2,4- triazole (4, 5) revealed the formation of
centrosymmetric dimers linked by strong O-H….N1Tr hydrogen bonds. The Schiff bases
obtained from the unsymmetrical 3-methyl,5-phenyl-1,2,4-triazole was found to be a
different E-conformer which was determined through solution NMR and
crystallographic diffraction analysis (13). The molecular geometry of the unsymmetrical
triazole derivatives: hemiaminal (12) and Schiff base (13) were also optimized using
density functional theory (DFT/M062x) method with the 6-311++G(d,p) basis set in
ground state and compared with the experimental data.
Keywords : 4-amino-1,2,4-triazole, chemical reactivity, hemiaminals, Schiff bases ,X-
ray structures, DFT.
1. Introduction
1

Schiff base compounds have been extensively investigated due to their wide
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range of applications in various fields of science and industry [1-5]. The azomethine
groups are present in various natural compounds and the -C=N- linkage is essential for
biological activity. In recent years, Schiff bases derivatives of 3(5)-aryl substituted 4-
amino-1,2,4-triazole and its complexes were reported to possess antibacterial [6-10],
antifungal [11-13], antioxidant and antiradical [14], antitumor [15, 16] and
antitubercular [17] activities. Furthemore, the 3,5-diaryl-1,2,4-triazole Schiff bases
derivatives upon chelation to metals show photochemical and photophysical properties
[18- 20]. One of them, the metallophthalocyanine zinc complex was examined as a
photosensitizers for the photocatalytic reactions [21].
Chemical species containing the azomethine group can be synthesized from the
primary amine by nucleophilic addition to carbonyl compounds. The reaction creates at
first an usually unstable intermediate tetrahedral product called hemiaminal, and then
after dehydration the stable imine is formed [22].
In our earlier investigations we have shown that 4-amine-1,2,4-triazole [23, 24]
and 4-amine-3,5-dimethyl-1,2,4-triazole [25] can react with benzaldehydes to give
stable hemiaminals and Schiff bases. We have examined the effects of the benzaldehyde
substituents and reaction conditions on the product distribution and stability [25]. These
results prompted us to look at the condensation reaction with the aryl substituted 4-
amino-1,2,4-triazoles. The present paper describes the synthesis, spectroscopic and
molecular structure study of novel hemiaminals and Schiff bases obtained from 4-
amino-3,5-diphenyl-1,2,4-triazole, 4-amino -3,5-dipyridin-2-yl-1,2,4-triazole and 4-
amino-3-methyl,5-phenyl-1,2,4-triazole.
2. Experimental
2.1 Materials and Physical Measurements
The reagents and solvents employed were commercially available and used as received
without further purification. Elemental analyses were carried out with a CHNS Vario
EL III analyzer. The NMR spectra were recorded on a Bruker 300 or 500 MHz
spectrometer using solvent as an internal standard. The chemical shifts are reported in
ppm and COSY, HMQC and HMBC were routinely used to definitely assign the signals
1
13
of H and C. The mass spectra of electrospray ionization (ESI)-MS were obtained on
MicrOTOF-Q mass spectrometer. The Fourier transform IR spectra were recorded from
KBr pellets in the range of 400-4000 cm-1 on a Bruker IFS 66 FT-IR. Flash
chromatography was performed on a Sepacore Flash System (Büchi Pump Module C-
605, Büchi Pump Manager C-615, Büchi UV Monitor C-630, Büchi Fraction Collector
C-660; Büchi Labortechnik, Flawil, Switzerland) using Merck silica gel (0.040–0.063
mm, 230–400 mesh).
2.2 X-ray Crystallography
2

Single crystal X-Ray diffraction data were collected at a Kuma KM4CCD four-circle
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diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71073 A ˚ ) at 100
K using an Oxford Cryosystem adapter [26]. and CC. Data collection and data reduction
CrysAlisPro, Agilent Technologies [27] program used. The structures were solved by
direct methods with SHELXS and was refined by a full-matrix least squares method
using SHELXL97 programs [28]. CCDC 1424617-1424619 contain the supplementary
crystallographic data for this paper. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: deposit@ccdc.cam.ac.uk).
2.3 Computational Methods
The calculations were carried out using Gaussian09 program [29]. The DFT method
with the M062x density functional [30] and 6-311++G(d,p) basis set [31, 32] have been
applied. The effect of solvent was simulated using SCRF method [33] with the
dielelctric constant for DMSO.
2.4 Preparation of compounds
2.4.1 Synthesis of amines 1-3
4-amino-3,5-dipyridin-2-yl-4H-1,2,4-triazole (1) and 4-amino-3,5-diphenyl-4H-
1,2,4-triazole (2) were synthesized in accordance with the published procedure and
checked with NMR spectra and elemental analysis [34].
Synthesis of 4-amino-3-methyl-5-phenyl-4H-1,2,4-triazole (3) Benzonitrile (2.55
.
mL, 25 mmol), acetonitrile (2.61 mL, 50 mmol), NH2NH2 H2O (80%, 9 mL) and
anhydrous ethanol (3 mL) were mixed in a 100 mL Teflon-lined autoclave and heated
o
for 3 days at 120 C. After cooling to room temperature the solvent was removed in
vacuum and the residue was washed with benzene (3X3mL). The insoluble part in
benzene was recrystallized from 1-propanol to afford a mixture of three products. Pure
samples were obtained by the separation method using flash Silica Gel chromatography
with 1-propanol as eluent. Three fractions were collected. First it was 4-amino-3,5-
dimethyl-4H-1,2,4-triazole (0.1654 g.). The 4-amino-3-methyl-5-phenyl-4H-1,2,4-
triazole (1.6782 g.) (3) was eluted next and the 4-amino-3,5-diphenyl-4H-1,2,4-triazole
(0.5200 g.) (2) was collected as a third fraction.
4-amino-3,5-diphenyl-4H-1,2,4-triazole (0.5200 g.) (2) Anal. Calc. (%) for
C14H12N4: C, 71.17;H, 5.12; N, 23.71. Found: C, 71.20;H, 4.98; N, 23.86. IR ( KBr,
cm-1): 492w; 604w; 687vs; 700vs; 725w; 763s; 769s; 916m; 928w; 968w; 1074w;
1109vw; 1269vw; 1287w; 1356vw; 1418w; 1454w; 1475s; 1628w; 3045w; 3212w;
3275w; 3362m. MS (ESI, m/z): 237.1 [M+H]+; 259.1 [M+Na]+, 275.1 [M+K]+, 495.2
1
[2M+Na]+. H-NMR (DMSO-d6, 295 K, ppm, 500 MHz): δ = 8.05 (dd,4H , J2-3 = 8.11
Hz, J2-4 = 1.62 Hz Ph-H2 ); 7.55 (m, 6H, Ph-H3,H4); 6.29 (s, 2H, NH2). 13C-NMR
(DMSO-d6, 295 K, ppm, 151 MHz): δ = 154.7 (Tr-C), 130.0 (Ph-C4), 128.9 (Ph-C3),
128.8 (Ph-C2), 127.8 (Ph-C1).
3

4-amino-3-methyl-5-phenyl-4H-1,2,4-triazole (1.6782 g.) (3) Anal. Calc. (%) for
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C9H10N4: C, 62.05;H, 5.79; N, 32.16. Found: C, 62.03;H, 5.65; N, 32.27. IR ( KBr, cm-
1): 473w, 486w, 559s, 642w, 675w, 693vs, 715vs, 722s, 753m, 777s, 921w, 964s, 989s,
1003s, 1057w, 1080w, 1269m, 1288w, 1346m, 1353m, 1363m, 1381w, 1421s, 1446s,
1461m, 1481vs, 1527s, 1536s, 1648s, 2926w, 2991w, 3151m, 3183m, 3253m. MS (ESI,
1
m/z): 175.1 [M+H]+; 197.1 [M+Na]+, 371.1 [2M+Na]+. H-NMR (DMSO-d6, 295 K,
ppm, 500 MHz): δ = 8.01 (d,2H , J2-3 = 8.01 Hz, Ph-H2 ); 7.49 (m, 3H, Ph-H3,H4); 6.02
13
(s, 2H, NH2); 2.37 (s, 3H, CH3) . C-NMR (DMSO-d6, 295 K, ppm, 126 MHz): δ =
153.2 (Tr-C-CH3), 152.2 (Tr-C-Ph), 129.2 (Ph-C4), 128.3 (Ph-C3), 127.7 (Ph-C2), 127.6
(Ph-C1), 9.9 (CH3).
2.4.2 Synthesis of hemiaminals 4-12
Compounds 4-6 were synthesized according to the following general procedure.
The corresponding aldehyde (0.34 mmol) in acetonitrile (2 mL) was added to a solution
of compound 1 (0.34 mmol) in 2.5 ml of acetonitrile and the mixture was then stirred
and heated at 50oC for 9 hours. After removing volatile components, raw solid products
washed with cold acetonitrile, methanol and dried in air. Crystals of hemiaminals were
obtained upon slow evaporation of the solvent from the reaction mixtures.
(4H-3,5-Dipyridin-2-yl-1,2,4-triazole-4-ylamino)(2,4-dinitrophenyl)methanol (4)
Yield 60 %. Anal. Calc. (%) for C19H14N8O5: C, 52.78;H, 2.80; N, 25.92. Found: C,
52.63;H, 3.04; N, 25.99. IR ( KBr, cm-1): 404m, 448w, 496w, 506w, 599m, 614m,
639w, 674m, 697s, 711s, 736vs, 752m, 791vs, 816vs, 835m, 863m, 892m, 913m, 972m,
992m, 1000m, 1050s, 1088s, 1133m, 1162w, 1184m, 1251w, 1286m, 1349vs, 1423m,
1444vs, 1474s, 1532vs, 1569m, 1594s, 3068m, 3105m. MS (ESI, m/z): 433.1 [M-H]+;
457.1 [M+Na]+. 1H-NMR (DMSO-d6, 295 K, ppm, 500 MHz): δ = 8.75 (d,1H , J(C-H)-(N-
= 8.24 Hz, N-H ); 8.73 (dd, 2H, J5-6 = 4.77 Hz, J4-6 = 0.60 Hz, Py-H6); 8.58 (d, 1H,
H)
J3-5 =2.29 Hz, Ar-H3); 8.54 (dd, 1H, J5-6 =8.70 Hz, J3-5 = 2.29 Hz, Ar-H5); 8.09 (d, 2H,
J3-4 = 7.78 Hz, Py-H3);8.03 (dd, 2H, J3,5-4 = 7.70 Hz, J4-6 = 1.70 Hz, Py-H4); 7.94 (d, 1H,
J5-6 = 8.70 Hz, Ar-H 6);. 7.59 (m, 2H, J4,-5 = 7.66 Hz, J5-6 = 4.77 Hz, J3-5 = 0.92 Hz, Py-
H5); 7.44 (d, 1H, J(C-H)-(O-H) = 5.49 Hz, O-H); 6.49 (dd, 1H, , J(C-H)-(N-H) = 8.24 Hz , J(C-H)-
(O-H) = 5.49 Hz, C-H). 13C-NMR (DMSO-d6, 295 K, ppm, 151 MHz): δ = 152.1 (Tr-C),
149.4 (Py-C6), 148.8 (Ar-C2), 148.0 (Ar-C4), 147.2 (Py-C2), 141.7 (Ar-C1), 138.3 (Py-
C4), 132.5 (Ar-C5), 132.2 (Ar-C6), 125.4 (Py-C5), 124.3 (Py-C3), 122.7 (Ar-C3), 83.9 (C-
OH).
Crystal data (C19H14N8O5): M=434.38,crystal system: triclinic, space
group: P-1, a = 10.414(4) Å, b = 10.596(4) Å, c = 18.168(6) Å, α = 105.31(3)o, β =
94.61(3)o, γ = 107.79(3)o, V = 1812.6(11) Å3, Z = 4, ρc = 1.592 g cm-3, ꢀ = 0.121 mm,
θmax = 36.8o, reflections: 20420, independent : 10275, Rint = 0.0593, R1 =0.0679, wR2
= 0.1738, GoF = 0.995.
(4H-3,5-Dipyridin-2-yl-1,2,4-triazole-4-ylamino)(2-chloro,5-
nitrophenyl)methanol (5) Yield 60 %. Anal. Calc. (%) for C19H14ClN7O3: C, 53.85; H,
3.33; N, 23.13;Cl, 8.37. Found: C, 53.83; H, 3.36; N, 23.29; Cl, 8.24. IR ( KBr, cm-1):
4

405w, 464w, 528w, 591m, 607w, 622w, 626w, 633w, 680w, 701m, 711m, 725m,
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741vs, 795s, 819m, 831w, 875m, 919w, 946w, 975w, 995w, 999w, 1007w, 1031vs,
1047m, 1079m, 1088m, 1104m, 1138w, 1151w, 1182w, 1193w, 1248m, 1284m,
1343vs, 1434s, 1443s, 1452s, 1463m, 1473m, 1519vs, 1571s, 1590s, 1611m, 3081w,
3132w. MS (ESI,CH3OH, m/z): 446.1 [2M+CH3OH+H2O ]+2; 477.6 [2M+Na+CH3
1
ONa+2H2O]+2. H-NMR (DMSO-d6, 295 K, ppm, 500 MHz): δ = 8.74 (m, 2H, J5-6
=
4.12 Hz, J4-6 = 1.83 Hz, J3-6 = 0.92 Hz, Py-H6); 8.54 (d,1H , J(C-H)-(N-H) = 7.92 Hz, N-H
); 8.21 (d, 1H, J4-6 =2.75 Hz, Ar-H6); 8.13 (dd, 1H, J3-4 =8.70 Hz, J4-6 = 2.75 Hz, Ar-H4);
8.10 (d, 2H, J3-4 = 7.78 Hz, Py-H3);8.04 (m, 2H, J4-5 = 7.52 Hz, J3-4 = 7.78 Hz, J4-6
1.83 Hz, Py-H4); 7.63 (d, 1H, J3-4= 8.70 Hz, Ar-H 3);. 7.59 (m, 2H, J4-5 = 7.52 Hz, J5-6
=
=
4.77 Hz, J3-5 = 1.40 Hz, Py-H5); 7.27 (d, 1H, J(C-H)-(O-H) = 5.53 Hz, O-H); 6.36 (dd, 1H, ,
13
J(C-H)-(N-H) = 7.92 Hz , J(C-H)-(O-H) = 5.53 Hz, C-H). C-NMR (DMSO-d6, 295 K, ppm,
151 MHz): δ = 152.4 (Tr-C), 149.4 (Py-C6), 147.1 (Py-C2), 146.9 (Ar-C5), 139.7 (Ar-
C1), 138.9 (Ar-C2), 138.2 (Py-C4), 131.3 (Ar-C3), 125.3 (Py-C5), 125.4 (Py-C5), 125.2
(Ar-C4), 124.1 (Py-C3), 81.1 (C-OH).
Crystal data (C19H14ClN7O3): M=423.82,crystal system: triclinic, space
group: P-1, a = 10.131(1) Å, b = 10.223(1) Å, c = 10.312(1) Å, α = 67.54(3)o, β =
71.38(3)o, γ = 89.99(3)o, V = 926.3(3) Å3, Z = 2, ρc = 1.520 g cm-3, ꢀ = 0.246 mm,
θmax = 36.7o, reflections: 8867, independent : 4497, Rint = 0.0760, R1 =0.0589, wR2 =
0.0809, GoF = 0.945.
(4H-3,5-Dipyridin-2-yl-1,2,4-triazole-4-ylamino)(4-chloro,3-
nitrophenyl)methanol (6) Yield 64 %. Anal. Calc. (%) for C19H14ClN7O3: C, 53.85; H,
3.33; N, 23.13;Cl, 8.37. Found: C, 53.89; H, 3.16; N, 23.30; Cl, 8.73. IR ( KBr, cm-1):
402w, 704m, 743s, 790s, 1049s, 1065m, 1093m, 1156w, 1186w, 1208w, 1267w,
1284w, 1349s, 1433s, 1452s, 1441m, 1466m, 1501w, 1532vs, 1568s, 1590m, 3125m.
1
MS (ESI,CH3OH, m/z): 446.1 [M+Na ]+; 477.6 [2M+Na+CH3 ONa+CH3OH]+2. H-
NMR (DMSO-d6, 295 K, ppm, 500 MHz): δ = 8.76 (d, 2H, J5-6 = 4.12 Hz, Py-H6); 8.52
(d,1H , J(C-H)-(N-H) = 7.78 Hz, N-H ); 8.17 (d, 2H, J3-4 =7.78 Hz, Py-H3); 8.09 (s, 1H, Ar-
H2); 8.06 (dd, 2H, J3,5-4 = 7.70 Hz, J4-6 = 1.70 Hz, Py-H4); 7.76 (m, 2H, Ar-H5,6);. 7.23
(d, 1H, J(C-H)-(O-H) = 5.49 Hz, O-H); 6.14 (dd, 1H, , J(C-H)-(N-H) = 7.78 Hz , J(C-H)-(O-H)
=
5.49 Hz, C-H). 13C-NMR (DMSO-d6, 295 K, ppm, 151 MHz): δ = 152.1 (Tr-C), 149.4
(Py-C6), 147.5 (Ar-C3), 147.2 (Py-C2), 141.4 (Ar-C1), 138.3 (Py-C4), 132.5 (Ar-C6),
132.2 (Ar-C5), 125.4 (Ar-C4), 125.3 (Py-C5), 124.4 (Ar-C2), 124.1 (Py-C3), 81.1 (C-
OH).
Compounds 7-10 were obtained from 4-amino-3,5-dipyridin-2-yl-1,2,4-triazole
(1) (0.172 mmol) and equimolar amounts of the corresponding aldehyde (0.172 mmol)
in hexane (2 mL). The reaction mixture was stirred and heated at 50oC for 9 hours. The
solvent was evaporated and the solids were washed two times with acetonitrile and
dried in air.
(4H-3,5-Dipyridin-2-yl-1,2,4-triazole-4-ylamino)(2-nitrophenyl)methanol
(7)
Yield 55 %. Anal. Calc. (%) for C19H15N7O3: C, 58.61; H, 3.88; N, 25.18, Found: C,
58.58; H, 3.81 ;N, 25.10 . . IR ( KBr, cm-1): 395w, 404w, 494w, 533w, 603m, 622m,
634w, 672m, 692s, 712s, 737vs, 770m, 789vs, 819m, 855m, 889m, 974m, 999m, 1050s,
1098s, 1153m, 1189m, 1251m, 1282m, 1291m, 1359vs, 1418s, 1443vs, 1473s, 1500m,
5

1527vs, 1569s, 1592vs, 2923m, 3046s, 3129s, 3198s, 3280s. 1H-NMR (DMSO-d6, 300
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K, ppm, 300 MHz): δ = 8.74 (d, 2H, J5-6 = 4.53 Hz, Py-H6); 8.63 (d,1H , J(C-H)-(N-H)
=
=
8.31 Hz, N-H ); 8.12 (d, 2H, J3-4 =7.93 Hz, Py-H3); 8.06 (dd, 2H, J3,5-4 = 7.55 Hz, J4-6
1.51 Hz, Py-H4); 7.79 (m, 1H, Ar-H5);. 7.75 (m, 1H, Ar-H6); 7.68 (m, 1H, Ar-H3);7.60
(m, 2H, J4-5 = 7.55 Hz, J5-6 = 4.53 Hz; J3-5 = 1.32 Hz; Py-H5); 7.58 (dd, 1H, J3,5-4 = 7.55
Hz, J4-6 = 1.32 Hz; Ar-H4); 7.14 (dd, 1H, J(C-H)-(O-H) = 5.48 Hz, O-H); 6.39 (dd, 1H, , J(C-
= 8.31 Hz , J(C-H)-(O-H) = 5.48 Hz, C-H). 13C-NMR (DMSO-d6, 300 K, ppm, 75
H)-(N-H)
MHz): δ = 152.1 (Tr-C), 149.1 (Py-C6), 148.9 (Ar-C2), 147.1 (Py-C2), 138.0 (Py-C4),
133.4 (Ar-C1), 133.3 (Ar-C6), 130.0 (Ar-C4), 128.4 (Ar-C3), 125.0 (Py-C5), 124.0 (Ar-
C5), 123.8 (Py-C3), 80.7 (C-OH).
(4H-3,5-Dipyridin-2-yl-1,2,4-triazole-4-ylamino)(3-nitrophenyl)methanol
(8)
Yield 63 %. Anal. Calc. (%) for C19H15N7O3: C, 58.61; H, 3.88; N, 25.18, Found: C,
58.45; H, 3.92 ;N, 25.09. IR ( KBr, cm-1): 590w, 631w, 681w, 702m, 714m, 732m,
744m, 792m, 804w, 868w, 922w, 975w, 998w, 1052m, 1061m, 1075m, 1092m, 1152w,
1209w, 1251w, 1302w, 1352s, 1433s, 1449m, 1464s, 1464s, 1481w, 1526vs, 1569m,
1
1587s, 2924m, 3095m, 3209s. H-NMR (DMSO-d6, 298 K, ppm, 300 MHz): δ = 8.78
(d, 2H, J5-6 = 4.08 Hz, Py-H6); 8.51 (d,1H , J(C-H)-(N-H) = 7.84 Hz, N-H ); 8.33(s, 1H, Ar-
H2); 8.18 (d, 2H, J3-4 =7.84 Hz, Py-H3); 8.20 (m, 1H, Ar-H4); 8.08 (t, 2H, J3,5-4 = 7.53
Hz, Py-H4); 7.92 (d, 1H, J5-6 = 7.52 Hz, Ar-H6);. 7.68 (t, 1H, J4,6-5 = 8.00 Hz, Ar-H6);
7.61 (t, 2H, J4,6-5 = 6.27 Hz, Py-H5); 7.15 (dd, 1H, J(C-H)-(O-H) = 5.64 Hz, O-H); 6.19 (t,
1H, J(C-H)-(N-H), (C-H)-(O-H) = 6.58 Hz, C-H). 13C-NMR (DMSO-d6, 298 K, ppm, 75 MHz):
δ = 152.1 (Tr-C), 149.3 (Py-C6), 148.1 (Ar-C3), 147.3 (Py-C1), 142.6 (Ar-C1), 138.3
(Py-C4)(Ar-C5), 133.5 (Ar-C2), 130.3 (Ar-C4), 125.3 (Py-C5), 124.1 (Py-C3), 121.8 (Ar-
C6), 84.4 (C-OH).
(4H-3,5-Dipyridin-2-yl-1,2,4-triazole-4-ylamino)(4-nitrophenyl)methanol
(9)
Yield 62 %. Anal. Calc. (%) for C19H15N7O3: C, 58.61; H, 3.88; N, 25.18, Found: C,
58.42; H, 3.83; N, 25.05. IR ( KBr, cm-1):403w, 469w, 589m, 623w, 634w, 677w,
694m, 701m, 714m, 737s, 797s, 815s, 856w, 895w, 970w, 999m, 1011w, 1047m,
1072m, 1107w, 1150w, 1198m, 1251w, 1248w, 1325m, 1346vs, 1392w, 1415m,
1
1435vs, 1466s, 1522vs, 1569m, 1589vs, 2925m, 3220s, 3293s. H-NMR (DMSO-d6,
300 K, ppm, 300 MHz): δ = 8.80 (d, 2H, J5-6 = 4.34 Hz, Py-H6); 8.52 (d,1H , J(C-H)-(N-H)
= 8.12 Hz, N-H ); 8.23(d, 2H,J2-3 = 8.50 Hz, Ar-H3,5); 8.17 (d, 2H, J3-4 =8.31 Hz, Py-
H3); 8.08 (dd, 2H, J3,5-4 = 7.74 Hz, J4-6 = 1.70 Hz, Py-H4); 7.76 (d, 2H, J2-3 = 8.50 Hz,
Ar-H2,6);. 7.61 (m, 2H, J4-5 = 7.46 Hz, J5-6 = 4.34 Hz, J3-5 = 1.13 Hz, Py-H5); 7.11 (dd,
1H, J(C-H)-(O-H) = 5.85 Hz, O-H); 6.21 (dd, 1H, J(C-H)-(N-H) = 8.12 Hz, J(C-H)-(O-H) = 5.85 Hz,
C-H). 13C-NMR (DMSO-d6, 300 K, ppm, 75 MHz): δ = 152.1 (Tr-C), 149.4 (Py-C6),
147.5 (Ar-C4), 147.3 (Py-C2), 145.3 (Ar-C1), 138.3 (Py-C4), 131.1 (Ar-C3,5), 128.3.5
(Ar-C2,6), 125.2 (Py-C5), 123.9 (Py-C3), 84.5 (C-OH).
(4-Cyanophenyl)(4H-3,5-dipyridin-2-yl-1,2,4-triazole-4-ylamino)methanol (10)
Yield 62 %. Anal. Calc. (%) for C19H15N7O3: C, 65.03; H, 4.09; N, 26.54, Found: C,
65.17; H, 4.01 ;N, 26.64. IR ( KBr, cm-1): 403w, 480w, 556w, 589w, 608w, 635w,
697m, 722w, 747m, 792s, 620m, 843w, 911w, 976w, 995w, 1019w, 1054m, 1060s,
1078m, 1149w, 1159w, 1188w, 1207w, 1249w, 1279w, 1407w, 1435vs, 1448s, 1459m,
1495m, 1568m, 1589s, 1609w, 2226s, 2926m, 3046s, 3075s, 3198s, 3208m. 1H-NMR
6

(DMSO-d6, 300 K, ppm, 300 MHz): δ = 8.79 (d, 2H, J5-6 = 4.15 Hz, Py-H6); 8.46 (d,1H
ACCEPTED MANUSCRIPT
, J(C-H)-(N-H) = 8.12 Hz, N-H ); 8.19 (d, 2H, J3-4 =7.93 Hz, Py-H3); 8.08 (dt, 2H, J3,5-4
=
7.74 Hz, Py-H4); 7.84 (d, 2H,J2-3 = 8.12 Hz, Ar-H3,5); 7.66 (d, 2H, J2-3 = 8.12 Hz, Ar-
H2,6);. 7.60 (m, 2H, J4-5 = 7.41 Hz, J5-6 = 4.15 Hz, J3-5 = 1.04 Hz, Py-H5); 7.05 (d, 1H,
J(C-H)-(O-H) = 5.67 Hz, O-H); 6.14 (dd, 1H, J(C-H)-(N-H) = 8.12 Hz, J(C-H)-(O-H) = 5.67 Hz, C-
13
H). C-NMR (DMSO-d6, 300 K, ppm, 75 MHz): δ = 152.1 (Tr-C), 149.4 (Py-C6),
147.3 (Py-C2), 145.7 (Ar-C1), 138.3 (Py-C4), 132.7 (Ar-C3,5), 127.9 (Ar-C2,6), 125.2
(Py-C5), 124.1 (Py-C3), 111.5 (Ar-CN), 100.0 (Ar-C4), 84.5 (C-OH).
(4H-3-Methyl,5-phenyl-1,2,4-triazole-4-ylamino)(2-nitrophenyl)methanol (11).
Compound 11 was prepared from 4-amino-3-methyl,5-phenyl-1,2,4-triazole (3) (0.040
g, 0.228 mmol) and 2-nitrobenzaldehyde (0.174 g, 1.152 mmol) in acetonitrile (3 mL).
The reaction mixture was stirred and heated at 50oC for 6 hours. The solvent was then
evaporated and the solid was washed two times with acetonitrile and one time with
methanol and dried in air. Yield 57 %. Anal. Calc. (%) for C16H15N5O3: C, 59.07;H,
4.65; N, 21.53. Found: C, 59.03 ;H, 4.57; N, .21.60. IR ( KBr, cm-1): 522w, 562w,
594w, 620w, 653w, 692vs, 709s, 722s, 743s, 770m, 789m, 841vw, 859w, 878w, 899w,
985w, 1007vw, 1029w, 1039w, 1063w, 1073w, 1116m, 1147w, 1158w, 1193w, 1203w,
1262m, 1295m, 1327m, 1342s, 1359s, 1383m, 1410m, 1447m, 1479s, 1523vs, 1557m,
1614w, 2885m, 2926m, 3217s, 3281s. MS (ESI, m/z): 326.1 [M-H]+; 348.1 [M+Na]+.
1H-NMR (DMSO-d6, 300 K, ppm, 300 MHz): δ = 7.83 (m, 2H,Ph-H2); 7.80 (d, 1H, J3-4
= 7.93 Hz, Ar-H3); 7.72 (d, 2H J = 4.15 Hz, Ar-H5,6); 7.55 (dt, 1H, J3,5-4 = 8.26 Hz, J4-6
= 4.27 Hz, Ar-H4); 7.43 (m, 3H, Ph-H3,4); 7.39 (d,1H , J(C-H)-(N-H) = 6.42 Hz, N-H ); 6.84
(d, 1H, J(C-H)-(O-H) = 5.48 Hz, O-H); 5.90(t, 1H, , J(C-H)-(N-H),(C-H)-(O-H) = 5.48 Hz, C-H);
2.51 (s, 1H, Tr-CH3). 13C-NMR (DMSO-d6, 300 K, ppm, 75 MHz): δ = 153.3 (Tr-
C(CH3), 152.0 (Tr-C(Ph), 147.9 (Ar-C2), 133.6 (Ar-C1), 133.0 (Ar-C5), 129.7 (Ar-C4),
129.1 (Ph-C4), 128.8 (Ph-C1), 128.2 (Ph-C3), 127.5 (Ph-C2), 123.8 (Ar-C3, C6 ), 78.6 (C-
OH), 10.7 (Tr-CH3).
(4H-3-Methyl,5-phenyl-1,2,4-triazole-4-ylamino)(2,4-dinitrophenyl)methanol
(12).
Compound was prepared from 4-amino-3-methyl,5-phenyl-1,2,4-triazole (3) (0.060 g,
0.345 mmol) and 2,4-dinitrobenzaldehyde (0.067 g, 0.345 mmol) in acetonitrile (4 mL)
in the same way as 11. Yield 60 %. Anal. Calc. (%) for C16H14N6O5: C, 51.89; H, 3.81;
N, 22.69. Found: C, 51.94; H, 3.85; N, .22.74. IR ( KBr, cm-1): 488w, 561m, 5598m,
617w, 641w, 693s, 716m, 739s, 770s, 837m, 857m, 920m, 1003m, 1057m, 1076m,
1126w, 1182m, 1246m, 1267m, 1343vs, 1410m, 1446m, 1479s, 1536vs, 1607s, 2730m,
2854m, 3115s, 3210s. MS (ESI, m/z): 393.1 [M+Na]+; 567.2 [2M-
1
C6H3(NO2)2CHO+Na]+, 763.2 [2M +Na]+. H-NMR (DMSO-d6, 300 K, ppm, 300
MHz): δ = 8.45 (d, br, 1H, J5-6 = 8.50 Hz, Ar-H5); 8.42 (s,br, 1H, Ar-H3); 7.82 (d,br, 1H,
J5-6 = 8.50 Hz, Ar-H6); 7.69 (d, br, 1H, J(C-H)-(N-H) = 5.48 Hz, N-H ); 7.60 (d, br, 1H, J2-3=
7.18 Hz, Ph-H2); 7.39-7.30 (m, 3H, Ph-H3,4); 7.21 (d, br, 1H, J(C-H)-(O-H) = 4.53 Hz, O-
13
H); 6.09(s, br, 1H, C-H); 2.53 (s, 1H, Tr-CH3). C-NMR (DMSO-d6, 300 K, ppm, 75
MHz): δ = 153.4 (Tr-C(CH3), 152.0 (Tr-C(Ph), 147.23 (Ar-C2), 147.17 (Ar-C4), 139.9
(Ar-C1), 130.3 (Ar-C6), 129.0 (Ph-C4), 128.6 (Ph-C1), 128.0 (Ph-C3), 127.4 (Ph-C2),
127.2 (Ar-C5 ), 119.4 (Ar-C3), 77.8 (C-OH), 10.9 (Tr-CH3).
7

ACCEPTED MANUSCRIPT
2.4.3 Synthesis of Schiff bases 13-20
Compound 13-18 were synthesized according to the general procedure . An
equimolar amount of compound 3 and carbonyl compounds (0.344 mmol) in acetonitrile
(4.5 mL) in presence of two drops of concentrated HCl was heated under reflux for 5
hours. After solvent removing the solid products washed with acetonitrile and methanol
and dried in air.
(N-(2-nitrobenzylidene)-
4H-3-methyl-5-phenyl-1,2,4-triazole-4-amine)
.
hydrochloride (13) Yield 80 %. Anal. Calc. (%) for C16H13N5O2 HCl: C, 55,90; H, 4,10;
N, 20,37; Cl, 10.31. Found: C,55.67; H, 4.12; N, 20.35; Cl, 10.43. IR ( KBr, cm-1):
376w, 495w, 593w, 646w, 656m, 692s, 704vs, 743s, 771m, 780m, 792m, 856s, 878w,
896m, 929m, 976s, 1001w, 1141m, 1230m, 1272m,1291m, 1342vs, 1371m, 1409w,
1439w, 1449m, 1527vs, 1568s, 1589m, 1597w, 1653w, 1830s, 2339br,vs, 2918w,
2995w, 3079w. MS (ESI, m/z, M=C16H13N5O2): 308.1 [M+H]+; 330.1 [M+Na]+, 346.1
[M+K]+. 1H-NMR (DMSO-d6, 295 K, ppm, 500 MHz) [for 1 and (2) isomers]: δ = 9.34
(9.27) (s, 1H, N=CH), 8.26 (8.25) (d, 1H, J3-4 = 8.01 Hz, Ar-H3); 8.10 (d, 1H, J5-6 = 7.63
Hz, Ar-H6); 7.98 (7.97) (t, 1H, J5-4,6 = 7.53 (7.63) Hz, Ar-H5); 7.92 (t, 1H, J3,5-4 = 7.06
(8.39) Hz, Ar-H4); 7.83 (m, 2H, Ph-H2); 7.58 (m, 3H, Ph-H3,4); 2.66 (2.60) (s, 1H, Tr-
CH3). 13C-NMR (DMSO-d6, 300 K, ppm, 75 MHz) [for 1 and (2) isomers]: δ = 167,4
(162.6) (N=CH), 149.8 (150.0) (Tr-C(CH3), 148.7 (148.7) (Tr-C(Ph), 148.2 (148.0) (Ar-
C2), 134.7 (134.6) (Ar-C5), 133.7 (133.5) (Ar-C4), 130.8 (130.4) (Ph-C4), 129.8 (129.7)
(Ar-C6), 129.0 (128.9) (Ph-C3), 128.4 (128.2) (Ph-C2), 126.4 (126.5) (Ar-C1), 125.1
(125.1) (Ar-C3), 124.8 (124.2) (Ph-C1), 10.7 (10.8) (Tr-CH3).
Crystal data (C16H14ClN5O2): M=343.77 ,crystal system: orthorhombic, space
group: P212121 , a = 7.165(2) Å, b = 10.585(3) Å, c = 20.678(5) Å, α = 90o, β = 90o, γ
= 90o, V = 1568.3(7) Å3, Z = 4, ρc = 1.456 g cm-3, ꢀ = 0.264 mm, θmax = 28.6o,
reflections: 10428, independent : 3722, Rint = 0.0228, R1 =0.0315, wR2 = 0.0886, GoF
= 1.013.
(N-(3-nitrobenzylidene)-
4H-3-methyl-5-phenyl-1,2,4-triazole-4-amine)
.
hydrochloride (14) Yield 91 %. Anal. Calc. (%) for C16H13N5O2 HCl: C, 55,90; H, 4,10;
N, 20,37; Cl, 10.31. Found: C,55.58; H, 3.92; N, 20.50; Cl, 10.60. IR ( KBr, cm-1):
660w; 675m; 694m; 709s; 737m; 747w; 776m; 788vw; 819w; 854m; 905w; 922w;
943w; 977s; 996 w; 1096w; 1142w; 1237w; 1292m; 1311m; 1332m; 1352vs; 1372m;
1408w; 1451m; 1478m; 1493 ; 1529vs; 1572w; 1591m; 1608s; 1849m; 2321m; 2582w;
2920w. MS (ESI, CH3OH, m/z, M=C16H13N5O2): 308.1 [M+H]+; 340.1
1
[M+H+CH3OH]+. H-NMR (DMSO-d6, 300 K, ppm, 500 MHz) [for E and (Z)
isomers]: δ = 9.16 (9.10) (s, 1H, N=CH), 8.75 (8.74) (t, 1H, J = 1.91 Hz, Ar-H2); 8.50
(8.48) (ddd, 1H, J4-5 = 8.22 Hz, J4-6 = 2.29 Hz, J2-4 = 0.96 Hz Ar-H4); 8.39 (8.37) (d, 1H,
J5-6 = 8.03 Hz, Ar-H6); 7.90 ((7.89) (t, 1H, J5-6 = 8.01 Hz, Ar-H5); 7.84-7.87 (7.82-7.86)
(m, 2H, Ph-H2); 7.51-7.59 (7.51-7.55) (m, 3H, Ph-H3,4); 2.65 (2.59) (2.60) (s, 1H, Tr-
CH3). ). 13C-NMR (DMSO-d6, 300 K, ppm, 126 MHz) (E isomer): δ = 167.0 (N=CH),
149.9 (Tr-C(CH3), 148.2 (Tr-C(Ph), 148.1 (Ar-C3), 134.5 (Ar-C6), 133.1 (Ar-C1), 131.0
(Ar-C5), 130.6 (Ph-C4), 128.9 (Ph-C3), 128.4 (Ph-C2), 127.5 (Ar-C4), 125.2 (Ph-C1),
124.1 (Ar-C2), 10.8 (Tr-CH3).
8

(N-(4-nitrobenzylidene)-
4H-3-methyl-5-phenyl-1,2,4-triazole-4-amine)
ACCEPTED MANUSCRIPT .
hydrochloride (15) Yield 75 %. Anal. Calc. (%) for C16H13N5O2 HCl: C, 55,90; H, 4,10;
N, 20,37; Cl, 10.31. Found: C,55.66; H, 4.12; N, 20.48; Cl, 10.73. IR ( KBr, cm-1):
577w; 629w; 634w; 678w; 691m; 698m; 711s; 748m; 780m; 849s; 889vw; 933m;
962w;978m; 1013w; 1025w; 1078vw; 1105w; 1139m; 1177w; 1240w; 1299m; 1334s;
1350vs; 1411w; 1423w; 1449m; 1464w; 1489w; 1524vs; 1580w; 1590m; 1604w;
1857m; 2353m; 2846w; 3032w; 3107w;. MS (ESI, CH3OH, m/z, M=C16H13N5O2):
308.1 [M+H]+; 340.1 [M+H+CH3OH]+. H-NMR (DMSO-d6, 300 K, ppm, 500 MHz)
1
[for 1 and (2) isomers]: δ =9.14 (9.08) (s, 1H, N=CH), 8.42 (8.42) (d, 2H, J2-3 =8.80 Hz,
Ar-H3,5); 8.20 (8.19) (d, 2H, J2-3 = 8.80 Hz, Ar-H2,6); 7.83-7.88 (m, 2H, Ph-H2) (7.84) (d
,2H, J2-3 = 7.10 Hz, J2-4 = 2.98 Hz, Ph-H2): 7.51-7.59 (7.50-7.56) (m, 3H, Ph-H3,4); 2.66
(2.61) (s, 1H, Tr-CH3). ). 13C-NMR (DMSO-d6, 300 K, ppm, 126 MHz) (isomer 1): δ =
166.9 (N=CH), 150.0 (Tr-C(CH3), 149.9 (Tr-C(Ph), 148.1 (Ar-C4), 137.1 (Ar-C1), 130.6
(Ph-C4), 130.4 (Ar-C2,6), 128.9 (Ph-C3), 128.4 (Ph-C2), 125.1 (Ph-C1), 124.3 (Ar-C3,5),
10.8 (Tr-CH3).
(N-(2,4-dinitrobenzylidene)-
4H-3-methyl-5-phenyl-1,2,4-triazole-4-amine)
.
hydrochloride (16) Yield 72 %. Anal. Calc. (%) for C16H12N6O4 HCl: C, 49,43; H, 3.37;
N, 21,62. Found: C,49.44; H, 3.40; N, 21.63. IR ( KBr, cm-1): 703s; 736w; 775m; 836s;
883m; 907w; 924w; 977m; 1059w; 1121w; 1140w; 1200w; 1231w; 1343vs; 1397w;
1450m; 1538vs; 1589s; 1848m; 2319m; 3086w. MS (ESI, m/z, M=C16H12N6O4): 353.1
[M+H]+; 371.1 [M+H+H2O ]+. 1H-NMR (DMSO-d6, 300 K, ppm, 500 MHz) [for 1 and
(2) isomers]: δ =9.36 (9.29) (s, 1H, N=CH), 8.88 (8.42) (d, 1H, J3-5 =2.29 Hz, Ar-H3);
8.73 (dd, 1H, J5-6 = 8.41 Hz, J3-5 = 2.29 Hz Ar-H5), (8.72) (dd, 1H, J5-6 = 8.24 Hz, J3-5
2.29 Hz, Ar-H5); 8,34 (d, 1H, J5-6 = 8.80, Ar-H6 ), (8.33) (d, 1H, J5-6 = 8.24, Ar-H6 ),
7.84 (dd ,2H, J2-3 = 6.12 Hz, J2-4 = 2.68 Hz, Ph-H2) (7.82) (dd ,2H, J2-3 = 6. 64 Hz, J2-4
=
=
2.98 Hz, Ph-H2): 7.56-7.60 (7.53-7.57) (m, 3H, Ph-H3,4); 2.66 (2.62) (s, 1H, Tr-CH3). ).
13C-NMR (DMSO-d6, 300 K, ppm, 126 MHz) (1 isomer): δ = 163.5 (N=CH), 150.2
(Tr-C(CH3), 149.3 (Tr-C(Ph), 148.7 (Ar-C2), 148.0 (Ar-C4), 131.7 (Ar-C1), 131.4 (Ar-
C6), 130.6 (Ph-C4), 128.9 (Ph-C3), 128.6 (Ar-C5), 128.4 (Ph-C2), 125.4 (Ph-C1), 120.3
(Ar-C3), 11.0 (Tr-CH3).
(N-(4-chloro-3-nitrobenzylidene)- 4H-3-methyl-5-phenyl-1,2,4-triazole-4-amine)
.
hydrochloride (17) Yield 78 %. Anal. Calc. (%) for C16H12ClN5O2 HCl: C, 50.81; H,
3.46; N, 18.52. Found: C,50.75; H, 3.32; N, 18.49. IR ( KBr, cm-1): 374m; 395m; 484w;
495w; 601vw; 689m; 705vs; 740w; 750w; 777m; 789m; 836m; 845w; 899w; 950s;
982s; 1003w; 1048m; 1140m; 1180w; 1205w; 1234w; 1290w; 1365m; 1456s; 1535s;
1589m; 1863m; 2226m; 2855s; 2925s. MS (ESI, m/z, M=C16H12ClN5O2): 342.1
[M+H]+; 360.1 [M+H+H2O ]+. 1H-NMR (DMSO-d6, 300 K, ppm, 500 MHz) [for 1 and
(2) isomers]: δ =9.14 (9.08) (s, 1H, N=CH), 8.65 (d, 1H, J2-6 =2.29 Hz, Ar-H2) (8.64) (d,
1H, J2-6 =1.83 Hz, Ar-H2); 8.24 (dd, 1H, J5-6 = 8.41 Hz, J2-6 = 1.91 Hz Ar-H6), (8.23)
(dd, 1H, J5-6 = 8.47 Hz, J2-6 = 2.06 Hz, Ar-H6); 8,02 (d, 1H, J5-6 = 8.41, Ar-H5 ), (8.02)
(d, 1H, J5-6 = 8.24, Ar-H5 ), 7.87 (dd ,2H, J2-3 = 7.46 Hz, J2-4 = 2.10 Hz, Ph-H2) (7.83-
7,87) (m ,2H, Ph-H2): 7.54-7.60 (7.51-7.57) (m, 3H, Ph-H3,4); 2.68 (2.63) (s, 1H, Tr-
CH3). ). 13C-NMR (DMSO-d6, 300 K, ppm, 126 MHz) (1 isomer): δ = 166.7 (N=CH),
149.7 (Tr-C(CH3), 148.2 (Tr-C(Ph), 147.8 (Ar-C3), 133,4 (Ar-C6), 132.8 (Ar-C5), 131,7
9

(Ar-C4), 130.9 (Ph-C4), 129,6 (Ar-C1) 129.0 (Ph-C ), 128.5 (Ph-C2), 126.3 (Ar-C2),
ACCEPTED MANU3SCRIPT
124.6 (Ph-C1), 10.7 (Tr-CH3).
(N-(2-chloro-5-nitrobenzylidene)- 4H-3-methyl-5-phenyl-1,2,4-triazole-4-amine)
.
hydrochloride (18) Yield 66 %. Anal. Calc. (%) for C16H12ClN5O2 HCl: C, 50.81; H,
3.46; N, 18.52; Cl, 18.75. Found: C,50.69; H, 3.22; N, 18.41; Cl, 18.29. IR ( KBr, cm-1):
451w; 462w; 480w; 533w; 595m; 698s; 710m; 741s; 776m; 792w; 842m; 908w; 936w;
946w; 967w; 989w; 1031w; 1050m; 1078w; 1118w; 1129w; 1182w; 1197w; 1249m;
1296m; 1348vs; 1374w; 1396m; 1413w; 1449m; 1474m; 1500w; 1529vs; 1610s;
1872m; 2266m; 2863w; 3061w; 3100w; 3164w. MS (ESI, m/z, M=C16H12ClN5O2):
342.1 [M+H]+; 360.1 [M+H+H2O ]+. 1H-NMR (DMSO-d6, 300 K, ppm, 500 MHz) [for
1 and (2) isomers]: δ =9.17 (9.11) (s, 1H, N=CH), 8.78 (d, 1H, J4-6 =2.68 Hz, Ar-H6)
(8.77) (d, 1H, J4-6 =2,75 Hz, Ar-H6); 8.45 (dd, 1H, J3-4 = 8.80 Hz, J4-6 = 2.68 Hz Ar-H4),
(8.44) (dd, 1H, J3-4 = 8.93 Hz, J4-6 = 2.98 Hz, Ar-H4); 7.96 (d, 1H, J3-4 = 8.80, Ar-H3 ),
(7,95) (d, 1H, J3-4 = 8.70, Ar-H3 ), 7.82 (dd ,2H, J2-3 = 7.65 Hz, J2-4 = 2.29 Hz, Ph-H2)
(7.78-7,82) (m ,2H, Ph-H2): 7.56-7.60 (7.53-7.59) (m, 3H, Ph-H3,4); 2.67 (2.63) (s, 1H,
Tr-CH3). ). 13C-NMR (DMSO-d6, 300 K, ppm, 126 MHz) (1 isomer): δ = 163.3
(N=CH), 149.7 (Tr-C(CH3), 148.6 (Tr-C(Ph), 146.8 (Ar-C5), 141,2 (Ar-C2), 132.1 (Ar-
C3), 130.8 (Ph-C4), 130,4 (Ar-C1) 129.1 (Ph-C3), 128.6 (Ph-C2), 128.4 (Ar-C4), 125.0
(Ph-C1), 123,1 (Ar-C6), 10.7 (Tr-CH3).
Compounds 19 and 20- were synthesized according to the following procedure.
The corresponding aldehyde (0.846 mmol) in glacial acetic acid (5 mL) was added to a
solution of compound 2 (0.846 mmol) in 5 mL of glacial acetic acid and the mixture
was then refluxed for 6 hours. After cooling the solution was poured into a beaker
containing 50 mL of ice water. The formed solid product was filtered. After drying in
vacuum, the product was recrystallized from ethanol.
(N-(4-nitrobenzylidene)- 4H-3,5-diphenyl-1,2,4-triazole-4-amine) (19) Yield 95
%. Anal. Calc. (%) for C21H15N5O2: C, 68.28; H, 4.09; N, 18.96. Found: C,67.91; H,
3.91; N, 18.66. IR ( KBr, cm-1): 497w; 513w; 611w; 620w; 632w; 677w; 693vs; 701vs;
750w; 773s; 780s; 851m; 860m; 931w; 962w; 981w; 1071w; 1283w; 1320m; 1351vs;
1376w; 1393w; 1446m; 1472s; 1522vs; 1596m; 1620w; 2861w; 3057w. MS (ESI, m/z,
1
M=C21H15N5O2): 370.1 [M+H]+; 392.1 [M+Na]+, 408.1 [M+K]+, 761.2 [2M+Na]+. H-
NMR (DMSO-d6, 300 K, ppm, 300 MHz): δ =8.71 (s, 1H, N=CH), 8.31 (d, 2H, J2-3
=8.67 Hz, Ar-H3,5); 8.00 (d, 2H, J2-3 = 8.67 Hz, Ar-H2,6); 7.79 (d ,4H, J = 5.07 Hz, Ph-
H2): 7.48 (dd, 4H, J= 5.07, 1.39 Hz, Ph-H3); 7.48 (d, 2H, J = 1.39 Hz, Ph-H4). 13C-NMR
(CDCl3, 298 K, ppm, 75 MHz): δ = 164.0 (N=CH), 150.8 (Ar-C4), 150.33(Tr-C(Ph),
136.8 (Ph-C1), 130.2 (Ar-C2,6), 129.6 (Ph-C4), 129.0 (Ph-C3), 128.7 (Ph-C2), 126.3 (Ar-
C1), 124.4 (Ar-C3,5).
(N-(2,4-dinitrobenzylidene)- 4H-3,5-diphenyl-1,2,4-triazole-4-amine) (20) Yield
96 %. Anal. Calc. (%) for C21H14N6O4: C, 60.87; H, 3.41; N, 20.28. Found: C,60.66; H,
3.21; N, 20.04. IR ( KBr, cm-1): 395w; 439w; 499w; 512w; 590w; 612m; 626s; 667m;
694vs; 710vs; 727m; 739m; 761s; 781vs; 835vs; 843m; 857w; 916s; 925m; 955m;
971w; 979w; 997w; 1010w; 1029w; 1070m; 1124w; 1151w; 1181m; 1202w; 1242m;
1282s; 1310s; 1347vs; 1384s; 1446m; 1471vs; 1536vs; 1596s; 1613s; 3058m; MS (ESI,
10

m/z, CH3OH, M=C21H14N6O ): 415.1 [M+H]+; 437.1 [M+Na]+, 453.1 [M+K]+, 469.1
4ACCEPTED MANUSCRIPT
1
[M+Na+ CH3OH]+, 851.2 [2M+Na]+, 883.2 [2M+Na+CH3OH]+. H-NMR (DMSO-d6,
295 K, ppm, 300 MHz): δ =8.92 (s, 1H, N=CH), 8.76 (d, 1H, J3-5 =2.31 Hz, Ar-H3);
8.67 (dd, 1H, J5-6 = 8.55 Hz, J3-5 = 2.31 Ar-H5); 8.35 (d ,1H, J5-6 = 8.55 Hz, Ar-H6): 7.80
(d, 4H, J= 5.01 Hz, Ph-H2); 7.54 (m, 4H, Ph-H3); 7.53 (m, 2H, Ph-C4). 13C-NMR
(DMSO-d6, 298 K, ppm, 75 MHz): δ = 165.0 (N=CH), 150.2 (Tr-C(Ph), 148.7(Ar-C2,4),
139.3 (Ph-C1), 131.0 (Ar-C6), 130.1 (Ph-C4), 129.0 (Ph-C3), 128.5 (Ph-C2), 128.5 (Ar-
C5), 126.0 (Ar-C1), 120.3 (Ar-C3).
3. Results and Discussion
The starting 4-amino-1,2,4-triazoles were prepared from nitriles and hydrazine
hydrate under solvothermal conditions (Scheme 1).
Scheme 1. Preparation of compounds 1-3.
The symmetrically 3,5-disubstituted -4-amino-1,2,4-triazoles can be simply
obtained from organonitriles RC≡N and hydrazine in the presence of sulfur or
hydrogenesulfide [35], in ethylene glycol [36, 37], dimethylformamide [38] or in one–
pot solvothermal conditions [34]. In contrast to that, the unsymmetrical 3,5-
disubstituted-4-amino -1,2,4-triazoles were synthesized in a multistep reaction or from
other noncommercial reagents as starting materials [39, 40]. When using nitriles only,
the 3-ethyl-5-methyl substituted compound was prepared from the equimolar amounts
of acetonitrile and propionitrile in the presence of sulfur, but the yield was low [41]. It
has been reported previously that in situ solvothermal generation of 4-amino triazoles
from hydrazine as a nucleophile to attack various organonitriles takes place by the way
of a multi-step process. The reaction involves the initial amidrazone formation (I) then
the 1,2-dihydrotetrazine (II) which undergoes rearrangement to the corresponding 4-
11

amino-triazole [34]. However to the best of our knowledge, this method to obtain
ACCEPTED MANUSCRIPT
unsymmetrical derivatives is unprecedented. In the condensation of acetonitrile and
benzonitrile (molar ratio 2:1 for the higher yield of 3) with hydrazine hydrate, a mixture
of symmetrically 3,5-disubstituted (dimethyl and diphenyl) and 3-methyl,5-phenyl-4-
amino-1,2,4-triazole (3) was obtained. The separation of products from the reaction
mixture was very easy using the normal phase liquid chromatography.
Upon treatment of 4-amino-1,2,4-triazoles (1-3) with various aromatic aldehydes
condensation reaction was expected to take place either to the hemiaminals (4-12 ) or
Schiff bases (13-20) (Scheme 2).
Scheme 2. Synthetic pathway for preparation of compounds 4 to 20.
3.1
Hemiaminals
Previous experimental and theoretical studies [23-25,42] on the condensation
reaction of 4-amino-1,2,4-triazoles with some substituted benzaldehydes showed that
the stability of the hemiaminals increased with the increase of electron-withdrawing
properties of the aldehyde substituents. Quantum-chemical calculations [42] indicated
also that modification of 4-amino-1,2,4-triazole in 3,5 position with almost all small
substituents with different electronic effect results in a favorable stabilization of
hemiaminal. It was also shown that lack the regularity which was observed for aldehyde
substituents. In order to explain how amine structure is affecting the formation and
stability of hemiaminals, the aryl substituted 4-amino-1,2,4-triazole derivatives were
examined and compared the received data with the previously obtained. The reactions
were usually carried out for 9 hours with the reactant ratio 1:1 using acetonitrile or
12

hexane as solvent at 50o C. Under these conditions, the reaction of 3,5-diphenyl amine
ACCEPTED MANUSCRIPT
(2) with substituted benzaldehydes (R= 2-NO2, 4-NO2, 2,4-(NO2)2, 4-Cl,3-NO2) has not
occurred. When the phenyl groups were slightly changed by replacement of a CH in
aromatic ring by N , 4-amino-3,5-dipyridyn-2-yl-1,2,4- triazole (1) was obtained which
was found to be a novel and efficient reagent for stable hemiaminal formation. Similar
compounds were also obtained from unsymmetrical 4-aminotriazole substituted by
phenyl and methyl groups. Subsequent studies on the effect of the substituents on the
selectivity of condensation reaction with 4-amino-triazoles showed that both the steric
and electronic effects play an important role in the product formation. The results are
summarized in Table 1.
Table 1
Substituent effects on the stable hemiaminal formation from 4-amino-3-R1,5-R2-1,2,4-
triazoles and aromatic aldehydesa (Ar-CHO)
R1, R2
Yield (%)
HA
HA/HA+SB
(%)
Ar
SB
2-NO2C6H4
R1=R2=H
76
27
43
24
0
2
4
7
35
0
97
82
86
41
0
R1=R2=CH3
R1=R2=2-py
R1=CH3, R2=Ph
R1=R2=Ph
4-NO2C6H4
R1=R2=H
70
18
34
0
6
0
3
0
0
92
100
92
0
R1=R2=CH3
R1=R2=2-py
R1=CH3, R2=Ph
R1=R2=Ph
0
0
2,4-(NO2)2C6H3
R1=R2=H
77
66
80
62
0
4
0
0
10
0
92
100
100
86
R1=R2=CH3
R1=R2=2-py
R1=CH3, R2=Ph
R1=R2=Ph
0
a. Reaction were carried out by mixing equimolar amounts of 4-amino-1,2,4-
triazole and aldehyde (0.172 mmol) in CH3CN (2 mL) at 50 oC for 9 hours.
Product yields were determined by the 1H NMR analysis of the crude
reaction mixture.
Increasing the steric bulk of the amine groups changes the reactivity of the
nitrogen atom. The increase of the size of C-substituents, R1 and R2 in the 4-amino-
1,2,4-triazoles, reduced the hemiaminal formation in the following order R1,R2=H,H;
CH3,CH3; CH3,Ph; Ph,Ph. Furthermore, for these substituents the steric effects seem to
much more powerful significant than the electronic ones. Isosteric replacement of
phenyl substituents by 2-pyridyl results in a significant change in reactivity. Different
nucleophilicity of the amine group probably results from electronic effects and from the
13

fact that in contrast to 2 [43], the H amino atoms of 1 participate in intramolecular H-
ACCEPTED MANUSCRIPT
bonds with the pyridyl N atoms as acceptors [44].
As shown in Table 2 the reactivity of benzaldehyde substrates with 1 was
affected by the number of the electron-withdrawing groups, their position and solvent
used. For the mono substituted benzaldehydes, the rate of hemiaminal formation is
slower in polar aprotic solvents such as CH3CN than in apolar aprotic solvents like
(hexane), similarly to that observed in the case of 3,5-dimethyl-1,2,4-triazole amine
[25].
Table 2
Benzaldehyde substituent and solvent effects on the hemiaminal and Schiff base
formation from the 4-amino-3,5-di-2-pyridyl-1,2,4-triazole (1)a.
solvent
Yield (%)
HA
HA/HA+SB
(%)
Ar
SB
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4-CNC6H4
CH3CN
Hexane
CH3CN
Hexane
CH3CN
Hexane
CH3CN
Hexane
CH3CN
CH3CN
CH3CN
43
71
25
46
34
71
41
69
80
49
98
7
11
0
0
3
6
9
4
0
0
0
86
87
100
100
92
92
82
95
2,4-(NO2)2C6H3
3-NO2,4-ClC6H3
2-Cl,5-NO2C6H3
100
100
100
a. Reactions were carried out by mixing equimolar amounts of 1 and aldehyde
(0.172 mmol) in solvent (2 mL) at 50 oC for 9 hours. Product yields were
determined by the 1H NMR analysis of the crude reaction mixture.
The formation of hemiaminals was confirmed by FT-IR, MS and NMR. Selected
spectral data and their assignments are listed in Table 3.
The bands due to NH2 and C=O groups that were present in the spectra IR of
substrates at 3344 cm-1, 3253 cm-1 and about 1700 cm-1 for di-pyridyl, methyl-phenyl
1,2,4-triazole amine and for benzaldehydes, respectively, disappeared from the infrared
spectra of compounds 4-12. The stretching vibrations of –OH and –NH groups were
found at 2500-3500 cm-1 as broad bands. This indicates that the hemiaminal molecules
in the solid state are linked by strong -O-H····NTr and -N-H····Npy hydrogen bonds. The
IR spectra of all hemiaminals show vibrational bands at 1569-1592 and 1418-1473
assigned for C=N and C=C vibrations. The strong bands observed in the IR spectrum of
4-9, 11 and 12 compounds at approximately 1350 and 1520 cm-1 can be assigned to the
NO2 group vibrations. The C≡N stretching vibration in 10 was present at 2226 cm-1. The
NMR spectra were obtained in the DMSO solution. It is obvious that solute and solvent
molecules must interact during the dissolution process. The hydrogen interaction
observed for hemiaminals in the solid state must be broken
14

ACCEPTED MANUSCRIPT
Table 3
Selected spectral data of hemiaminals R1C*H(OH)NHR2
vibration
13C
NMR
[ppm]
δ(C*)
frequencies [cm-1]
1H NMR δ[ppm], J[Hz]
R1
R2
ν(OH,.NH) ν(NO2),
ν(C≡N)
δ(NH) δ(OH) δ(CH) JCH-
JCH-
NH
OH
2,4-(NO2)2 C6H3 (4)
2-Cl, 5-NO2 C6H3
(5)
A
A
3105
3132
1349,1532 8.75 7.44 6.49 8.24 5.49 83.9
1343,1519 8.54 7.27 6.36 7.92 5.53 81.1
3-NO2,4-Cl C6H3 (6)
2-NO2 C6H4 (7)
3-NO2 C6H4 (8)
4-NO2 C6H4 (9)
4-CN C6H4 ( 10)
2-NO2 C6H3 (11)
A
A
A
A
A
B
3125
3198
3209
3220
3198
3217
1349,1532 8.52 7.23 6.14 7.78 5.49 81.1
1359,1527 8.63 7.14 6.39 8.31 5.48 80.7
1352,1526 8.51 7.15 6.19 7.84 5.64 84.4
1346,1522 8.52 7.11 6.21 8.12 5.85 84.5
2226
8.46 7.05 6.14 8.12 5.67 84.5
1359,1523 7.39 6.84 5.90 6.42 5.48 78.6
1343,1536 7.69 7.21 6.09 5.48 4.53 77.8
2,4-(NO2)2 C6H3 (12) B 3210
A- 3,5-di-2-pyridyl-1,2,4-triazole, B-3-methyl,5-phenyl-1,2,4-triazole.
and new ones, involving the oxygen atoms of DMSO and acidic protons –OH and -NH
were formed [45]. After the condensation reaction, absorptions at 7.82 for 1 and 6.02 for
3 (δNH2 group) disappeared from the 1H NMR spectra, and all compounds showed new
resonances assigned to the C-NH-N, C-OH and CH-N protons (Table 3). The
characteristic δ(C*) signal for hemiaminals R1C*H(OH)NHR2 at 77.8-84.5 ppm was also
observed in the 13C NMR. The room temperature 1H NMR spectrum of 12 is very broad
in every region, suggesting the presence of at least two conformers slowly
interconverting on the NMR scale. It is known that the vicinal H-H coupling magnitude
is a function of the dihedral angle between the protons [46]. Thus, the small coupling
3
constant J(CH-NH) for hemiaminal 12 (5.48 Hz) indicates that a transformation of
stretched molecule may occur in solution (dihedral angle about 170o) into a twisted one
(dihedral angle around 60o). Rotation about N(sp3) -C*(sp3) bond and the configuration
inversion on the N atom are the steps in that process. Scheme 3 shows a possible
interconversion pathway for 12 in DMSO solution.
15

ACCEPTED MANUSCRIPT
Scheme 3. Possible interconversion pathway for 12 in DMSO solution.
Possible mechanism of interconversion for hemiaminal 12 was studied also by
means of quantum-chemical calculations (0 K). Relaxed scan of the potential energy
surface (PES) was performed for two dihedral angles: N-N-C-C and C-N-N-C. The
values of the angles were separately varied from -180 to 180o with step 6o. Local
minima obtained from the scan of PES were subsequently optimized to minimum of
total energy (Etot).
Conformational analysis performed for the N-N-C-C angle and subsequent
optimization of geometrical structure yielded two different local minima on PES for -
86o (Min1) and 47o (Min3). The optimized geometrical structures of both conformers
are presented at Figure 1a.
The Min1 conformer is about 5.1 kcal/mol more stable than Min3 conformer. Both
conformers are separated by two energy barriers that are local maxima of potential
energy with respect to rotation around the N-C single bond. The interconversion from
the Min1 to Min3 conformer requires supply of about 6 kcal/mol of energy (the energy
barrier for ≈ 0o) or 12 kcal/mol (the energy barrier for ≈ 130o). Conformational analysis
performed for the C-N-N-C angle showed also two local minima on PES for 97 and -74o
(Min2). The minimum of Etot found for 97o turned out to be very similar to the Min1
therefore it was not further studied. The Min2 conformer is only 3.9 kcal/mol less stable
than the Min1 conformer. The estimated value of the height of energy barrier between
Min1 and Min2 is about 9 kcal/mol. Taking into account small differences of the values
of Etot between all conformers and small values of the energy barriers our calculations
suggest that all three conformers of the hemiaminal may be experimentally observed.
16

ACCEPTED MANUSCRIPT
Figure 1. a) Optimised geometrical structures of the molecule of hemiaminal 12 that
were selected on the basis of conformational analysis performed for the N-N-C-C
(Min1, Min3) and C-N-N-C (Min2) dihedral angles. b) Optimized geometrical
structures of transition state (TS) and associated minima of the total energy for a process
of interconversion of the chirality of the nitrogen.
The analysis of configuration on the N atom for all points obtained from the relaxed
scans of PES for both dihedral angles has shown the interconversion of the chirality of
the nitrogen. The geometrical structures of the transition state (TS) and associated local
minima on PES obtained from geometry optimization, following the intrinsic reaction
coordinate, are shown at Figure 1b. The energy barriers are low (2.94 and 3.25
kcal/mol) and they are smaller than calculated for ammonia using CCSD(T) data (5.06
kcal/mol) [47]. This result suggests that a process of interconversion of the chirality of
the nitrogen in hemiaminal 12 is very probable under experimantal conditions.
The hemiaminals 4-10 are stable in the solid state for a long time period but in the
DMSO solution they decompose mostly to substrates (Figure 2).
17

ACCEPTED MANUSCRIPT
Figure 2. Decomposition of the hemiaminals 4-10 in DMSO solution as the function of
time.
In some cases, formation of the Schiff base was observed as a second step of the
benzaldehyde and 4-amino-3,5-di-2-pyridyl-1,2,4-triazole condensation, after water
elimination from hemiaminal molecules. The compounds 4, 5, 6, 8 and 9 with the
phenyl ring substituted by 2,4-(NO2)2; 2-Cl,5-NO2; 3-NO2,4-Cl; 3-NO2 and 4-NO2,
respectively, were transformed into the Schiff bases with : 5; 3; 37; 12 and 16 % yields,
after standing for 30 hours at room temperature in DMSO solution. Also compound 12
is not very stable in DMSO solution (40% of starting hemiaminal after 20 days). The
NMR spectra showed also signals corresponding to the -CH=N- Schiff base (δH=9.27
and δC=161.0 ppm), –CH(OH)2 aldehyde gem-diol (δH=6.25 (1H); 7.21(2H) and
δC=85.1 ppm) groups plus amino-triazole and benzaldehyde signals. The results show
also that the replacement of a hydrogen or methyl [25] by a phenyl or a 2-pyridyl group
in the triazole ring leads to decrease in the stability of these hemiaminals in DMSO
solution.
Single crystals of 4 and 5 suitable for X-ray analysis were obtained from acetonitrile
at room temperature by slow solvent evaporation. Molecular views of the compounds
are shown in Figure 3, and selected geometric parameters are given in Table 4.
Figure 3. Molecular view of new hemiaminals with atom labeling and
intramolecular hydrogen bonding (dashed lines).
18

Geometry of 4 and 5 displays significant similarities. The molecules are composed
ACCEPTED MANUSCRIPT
of the central 1,2,4,-triazole ring, substituted at the C8 , C14 and N3 atoms by two 2-
pyridyl and Cα-hydroxybenzylamino groups. The central heterocyclic ring is planar but
in contrast to amine 1 [44], not coplanar with its 2-pyridyl substituents. The pyridyl
rings are twisted about the external bond to the 1,2,4-triazole (Table 4). The most
noteworthy feature of these structures is the dissimilar orientation of the pairs of
pyridine rings. While in the molecule of 4 the pyridine nitrogen atoms point in opposite
direction, both pyridine nitrogen atoms in the molecule of 5 point away from the N2 unit
of the central five-membered heterocyclic ring.
Table 4
Selected geometric parameters for 4 and 5.
4
5
A
B
Bond lengths [Å]
C1-C7
C7-N4
N4-N3
C8-C9
C8-N1
C7-O7
N1-N2
1.532(3)
1.484(4)
1,425(3)
1,460(4)
1,321(3)
1.399(4)
1.378(3)
1.526(3)
1,485(4)
1,417(3)
1,477(4)
1,319(3)
1.400(4)
1.381(3)
1,515(4)
1,475(5)
1,422(4)
1,458(5)
1,322(4)
1.419(4)
1.388(3)
Torsion angle [o]
C1-C7-N4-N3
-170.5(2)
171.3(2)
173.0(2)
Dihedral angle [o]
20.5(8)
Phenyl-triazole
Pyridyl (1)-triazole
Pyridyl (2)-triazole
21.8(3)
10.4(3)
19.3(8)
8,3(5)
15,1(3)
22,9(5)
23.3(4)
22.4(3)
The later conformation was previously observed in most of the 4-substituted 3,5-
di(2-pyridyl)-1,2,4-triazoles [48]. The second one was only detected in crystals of 1-
(3,5-bis( pyrid-2-yl)-1,2,4-triazol-4-yl)-3-phenylurea [49], 3,5-di(2-pyridyl)-4-(1H-
pyrrol-1-yl)-4H-1,2,4-triazole and metal complexes [50].
Two aromatic rings, phenyl and triazole are linked through a N3-N4-C7-C1
fragment, central part of molecule. In the hemiaminals, the C7 and N4 atoms are
tetrahedral with sp3 and N3 and C1 are planar with sp2 hybrydization. The N3-N4-C7-
C1 torsion angle is determined by the type of molecules – either stretched or twisted
[23]. For 4 and 5 these torsion angles are about 170o (Table 4) and two stretched
stereoisomers RS and SR are formed. Structural analysis of 4 and 5 shows that similarly
to other hemiaminals derived from 1,2,4-triazoles [23-25], strong intermolecular
hydrogen bonds O-H···N2Tr exist. This type of almost linear interactions connecting two
stretched molecules leads to the formation of centrosymmetric dimers (RS-SR) (Figure
4).
19

ACCEPTED MANUSCRIPT
Figure 4. A view of part of the crystal structure of 4 showing the formation of the
hydrogen – bonded dimer and π-π interaction between aromatic rings.
The hydrogen bridges between the OH group and the nitrogen N2 atom of the
triazole ring in compounds 4 and 5 ( Table 5) are comparable to the corresponding bond
previously reported for (2,4-dinitrophenyl)(1,2,4-triazole-4-amino)methanol (O-H···NTr
1.81(2) Å, O·· NTr 2.744(2) Å , O-H-NTr angle 168(2)o) and (2,4-dinitrophenyl)(3,5-
dimethyl-1,2,4-triazole-4-amino)methanol (O-H···NTr 2.00(4) Å, O·· NTr 2.811(3) Å ,
O-H-NTr angle 161(3)o) dimers [23, 25]. The crystals packing is determined also by the
combination of strong N-H···Npy intramolecular and C-H···N, C-H···O, C-H···Cl weak
intra and intermolecular hydrogen bonds (Table 5, Figure 3). In addition to these
interactions, the crystal structures are stabilized by π-π interaction between aromatic
rings. Intermolecular π-π contacts in 4 occur between the two triazole rings (Cg1) (the
ring centroids distance from Cg1A to Cg1B is 3.143Å and offset distance is 1.110Å)
and pyridine rings (Cg2) (the ring centroids distance from Cg2A to Cg2B is 3.225 with
offset of 1.734 Å) (Figure 4). The distance between the triazole rings centroids in dimer
5 is 3.275 and the offset is 1.093 Å.
Table 5
Geometry of proposed hydrogen bonds for 4 and 5
D-H···A [Å]
D-H [Å]
H···A [Å]
D···A [Å]
<D-H···A [°]
4
O(7B)-H(70B)···N(2A)
O(7A)-H(70A)···N(1B)
O(7A)-H(70A) ··N(2B)
C(5B)-H(5B) ··O(4A)(i)
C(6B)-H(6B)···O(7B)(ii)
C(6A)-H(6A)···O(7A)(iii)
0.84(3)
2.15(3)
2.61(3)
1.84(3)
2.48(3)
2.50(3)
2.54(3)
2.925(3)
154(3)
141(2)
165(3)
135(3)
123(2)
135(3)
0.97(3)
0.97(3)
0.95
3.412(3)
2.787(3)
3.226(4)
3.117(4)
3.283(4)
0.95
0.95
20

C(13B)-H(13B)···O(4A)(i) 0.95
C(13A)-H(13A)··O(4B)(iv) 0.95
2.50(3)
3.442(3)
171(3)
141(3)
156(3)
138(3)
152(3)
144(3)
159(3)
152(3)
129(2)
140(3)
150(3)
125(3)
125(3)
105(4)
119(3)
122(2)
ACCEPTED MANUSCRIPT
2.43(3)
2.41(5)
2.42(3)
2.42(3)
2.56(3)
2.56(3)
2.61(3)
2.59(3)
2.15(3)
2.00(3)
2.32(3)
2.36(3)
2.61(3)
2.41(3)
2.39(3)
3.225(3)
C(18A)-H(18A)···O(4)(v)
C(19B) -H(19B)···O(1A)
C(19A)-H(19A)···O(2B)
C(5B) -H(5B)···N(2A)(ii)
C(5A) -H(5A)···N(1B)(iii)
0.95
0.95
0.95
0.95
0.95
3.297(5)
3.186(3)
3.287(3)
3.379(4)
3.468(4)
3.481(4)
3.311(3)
2.830(3)
2.816(3)
3.004(4)
3.041(4)
3.024(4)
2.99\4(4)
3.006(4)
C(17A)-H(17A)···N(5A)(vi) 0.95
C(7B) -H(7B)···N(6A)
N(4B) -H(40B)···N(5B)
N(4A) -H(40A)···N(5A)
C(7B) -H(7B)···O(2B)
C(7A) -H(7A)···O(1A)
C(7A) -H(7A)···N(7A)
C(16B) -H(16B)···N(4B)
C(16A)-H(16A)···N(4A)
1.00(3)
0.83(3)
0.91(4)
1.00(3)
1.00(3)
1.00(3)
0.95
0.95
5
O(7) -H(70)···N(2)(vii)
C(12) –H(12)…O(1)(viii)
C(18) -H(18)···Cl(1)(ix)
N(4) -H(40)···N(5)
C(7) -H(7)···Cl(1)
0.84
1.94(3)
2.59(3)
2.81(3)
2.07(3)
2.62(3)
2.58(3)
2.763(3)
3.478(4)
3.653(4)
2.870(5)
3.120(3)
3.220(5)
168(2)
155(3)
148(2)
139(2)
111(2)
122(2)
0.95
0.95
0.96(3)
1.00(3)
1.00(3)
C(7) -H(7)··N(6)
Symmetry codes: (i) x,y,1+z ; (ii)1-x,1-y,1-z ; (iii)-x,1-y,-z ; (iv)-1+x,-1+y,-1+z ; (v)
2-x,2-y,1-z ; (vi)1-x,1-y,-z ; (vii) 1-x,1-y,-z, (viii) 2-x,1-y,1-z, (ix) -x,-y,1-z
3.2
Schiff bases
The 4-amino-3-methyl-5-phenyl-4H-1,2,4-triazole (3) when treated with various
substituted benzaldehydes in acetonitrile in presence of hydrochloric acid as a catalyst
formed corresponding Schiff base hydrochlorides 13-18. At the same condition 4-
amino-3,5-diphenyl-4H-1,2,4-triazole (2) has not reacted with benzaldehydes and
imines 19 and 20 could only be obtained after changing the solvent to acetic acid.
The structures of the Schiff bases were in accord with their spectroscopic data. The
IR spectra of compound 13-18 showed in the solid state strong, broad absorption bands
at 3400- 1800 cm-1 which were attributed to the stretching modes of triazolium C=N+-H
group. Generally, the absorption peaks corresponding to that group occurred at slightly
higher frequencies [51]. The appearance of these modes at lower frequencies may be
caused by the hydrogen bonding interactions with the chloride ion N+-H··Cl- exist
(Table 6). The spectra of 13-20 display also characteristic azomethine group stretching
21

band in the range of 1589-1653 cm-1 and strong bands at approximately 1350 and 1530
ACCEPTED MANUSCRIPT
cm-1 which can be assigned to the NO2 group vibrations.
Table 6
Selected spectral data of Schiff bases R1C*H=NR2.
vibration frequencies [cm-1]
NMR δ[ppm],
1H, (a) 13C,(a)
ν(N+H) ν(C=N+) ν(C*=N) ν(NO2) δ(C*H=N) δ(CH3) δ(C*)
R1
R2
2-NO2 C6H4 (13)
A
2339 1830 1653 1342
1527
(9.34)
9.27
(2.66) (167.4)
2.60 162.6
3-NO2 C6H4 (14)
A
A
A
A
A
B
B
2582 1849 1608 1352
(9.16)
9.10
(9.14)
9.08
(9.36)
9.29
(9.14)
9.08
(2.65) (167.0)
2.59
(2.66) (166.9)
2.61
(2.66) (163.5)
2.62
(2.68) (166.7)
2.63
2321
1529
4-NO2 C6H4 (15)
2359 1857 1604 1334
1524
2,4-(NO2)2 C6H3 (16)
4-Cl, 3-NO2 C6H3 (17)
2-Cl, 5-NO2 C6H3 (18)
4-NO2 C6H4 (19)
2319 1848 1589 1343
1538
2226 1863 1589 1365
1535
2266 1872 1610 1348
(9.17)
9.11
8.71
(2.67) (163.3)
2.63
1529
1620 1351
1522
1613 1347
1536
164.0
2,4-(NO2)2 C6H3 (20)
8.92
165.0
A-3-methyl,5-phenyl-1,2,4-triazole, B-3,5-diphenyl -1,2,4-triazole, a- after
recrystallization from methanol
1
The H NMR spectra of compounds 14-18 revealed the presence of two signals
belonging to the azomethine CH proton and the methyl triazole CH3 substituent at 9.08-
1
9.36 and 2.59-2.66 ppm, respectively. The appearance of these protons in the H NMR
spectrum of compound 13 as two sets of two singlets can be considered as a proof of the
formation of two isomers. It was reported in the literature [52] that compounds
possessing the azomethine linkage exhibit E and Z geometrical isomerism around -
C=N- double bond (Scheme 4). Moreover, the trans-isomers of Schiff bases are more
stable and photoinduced cis-isomers return spontaneously and very quickly to the E
1
form [53]. The H NMR signals of the cis and trans isomers of aromatic imines show
particularly large differences in their chemical shifts [52, 54]. Our data for compounds
13-18, and the slight differences observed after recrystallization from methanol allow
think that these compounds exist only as a E isomers but in different conformations
probably arising from the rotation around N-N single bond (Scheme 4).
22

ACCEPTED MANUSCRIPT
Scheme 4. Possible conformers of Schiff bases 13-18 obtained from 4-amino-3-methyl-
5-phenyl-4H-1,2,4-triazole (3).
The conformational preference of the Schiff base (shown at Scheme 4) was studied
by means of the PES scan with geometry optimization at each point at the M062x/6-
311++G(d,p) computational level (0 K) using SCRF method with the dielelctric
constant for DMSO. The C-N-N-C dihedral angle was varied between -180 and 180o
with step of 6o. The evolution of the total energy (Etot) of the Schiff base relative to a
value of the C-N-N-C dihedral angle is presented at Figure 5. The relationship between
values of Etot and dihedral angle was modelled using polynomial regression [55].
Four different local minima (Min1 - Min4 ) and four local maxima of Etot were
observed. The optimized geometrical structures of the conformers are presented at
Figure .5. The optimized value of the C-N-N-C dihedral angle equals respectively: -
146o (Min1), -50o (Min2), 47o (Min3) and 141o (Min4). The difference of the values of
the total energy between the most stable (Min1) and the less stable (Min4) confomer is
very small and equals only 1.60 kcal/mol. Similarly, the estimated heights of the energy
barrier associated with a rotation about the N-N bond are also very small (< 1.8
kcal/mol). Thus, the single molecule of Schiff base is floppy molecule and presumably
can be easily interconverted from one to another conformer.
Additionally conformer Min1 is stabilized by intramolecular C-H....O interaction
(ρ(3,-1)(r) = 0.007 e/bohr3, ∇2ρ(3,-1)(r) = 0.026 e/bohr5) between the methyl and NO2
groups.
23

ACCEPTED MANUSCRIPT
Figure 5. Evolution of the potential energy of the Schiff base relative to a rotation about
the N-N bond (the C-N-N-C dihedrial angle denoted by red circles, values in o) obtained
from conformational analysis. The values of the relative energy (in kcal/mol) are
calculated in respect to the total energy for Min2. The optimised geometrical structures
of the conformers (Min1 - Min4) correspond to four local minima observed in the graph
of the potential energy.
Single crystals of 13 were grown by slow evaporation of acetonitrile from the post-
reaction mixtures. The X-ray structure of 13 shows the E geometries of the C=N
azomethine double bond. The same configuration is expected for all 14-18 because the
3-methyl-5-phenyl-1,2,4-triazole-4-amine moiety is common to all of these compound
and the Z configuration would be higher in energy.
Figure 6. . Molecular view of Schiff base hydrochloride 13 with atom labeling.
24

The molecular view of compound 13 with atom-numbering scheme is shown in
ACCEPTED MANUSCRIPT
Figure 6 and selected geometric parameters are given in Table 7. The bond lengths and
angles are found to have normal magnitudes [56]. In the crystal structure two rings in
the phenyl-triazole fragment is not flat and the (N1T-N2T) triazole and (C4T-C9T)
phenyl rings make are not coplanar with dihedral angle of 12.5(2)o. The N4=C14 double
bond and the C1-C6 aromatic ring are also not coplanar. The C2-C1-C14-N4 torsion
angle is equal 152.1(2).
Table 7
Selected geometric parameters for 13.
Bond lengths [Å]
1.474(2)
Bond angles [o]
125.4(2)
C1-C14
C14-N4
N4-N3T
N2T-C2T
N1T-C1T
N1T-N2T
N4-N3-C2T
C1-C14-N4
N4-C14-C1
1.278(2)
1,419(2)
1,317(2)
1,318(2)
117.3(2)
117.2(1)
Torsion angle [o]
C2-C1-C14-N4
N3T-N4-C14-C1
152.1(2)
176.7(2)
1.361(2)
Dihedral angle [o]
Phenyl-triazole
31.0(2)
Phenyl(T)-triazole
12.5(2)
The dihedral angle between the triazole ring (N1T-N2T) and the phenyl one (C1-C6)
indicates that they are twisted from each other (31.0(2)o), which is quite different from
that found for (N-(4-nitrobenzylidene)-4H-3,5-Dimethyl-1,2,4-triazole-4-amine)
hydrochloride (70.48(2)o) [25]. The differences between these two compounds are
mainly due to hydrogen bonding interaction between disordered orto CH groups on the
C4T-C9T ring and either N1T and N4 atoms (see Table 8). The strong N2T-H10T···Cl
and weak C-H···O, C-H···Cl intermolecular interactions also occur.
Table 8
Hydrogen bonding geometry for compound 13.
D-H···A [Å]
N(2T)-H(10T)...Cl(1)
C(4)-H(4)...O(1)(i)
C(6)-H(6)...Cl(1)(ii)
C(14)-H(14)...Cl(1)(iii)
C(5T)-H(5T)...N(4)
C(9T)-H(9T)...N(1T)
C(14)-H(14)...O(2)
D-H [Å]
0.98(2)
0.95
H···A [Å]
2.00(2)
2.54
D···A [Å]
2.967(2)
3.206(3)
3.445(2)
3.530(2)
3.030(2)
2.816(2)
2.668(2)
<D-H···A [°]
169
127
0.95
2.77
128
0.95
2.61
162
0.95
2.36
127
0.95
2.49
100
0.95
2.82(2)
101
Symmetry codes: (i) 1-x,-1/2+y,1/2-z; (ii) x,-1+y,z, (iii) 1/2+x,3/2-y,1-z
25

ACCEPTED MANUSCRIPT
In addition, the crystal structures are stabilized by π-π interaction between aromatic
rings. An intermolecular π-π contacts in 13 occurs between the triazole (Cg1) , phenyl
(Cg2) and phenyl(T) (Cg3) rings (the ring centroids distance from Cg1 to Cg2 is 3.432
Å with offset distance 0.964 Å and from Cg2 to Cg3 is 3.982 Å with offset 1.117 Å).
4. Conclusions
In this study the simple one-pot method was established for the synthesis of 4-
amino-3-methyl-5-phenyl-1,2,4-triazole (3). A series of new hemiaminals were
synthesized by introduction of 3 or 4-amino-3,5-dipyridin-2-yl-1,2,4-triazole to
aromatic aldehydes. We found that increasing the steric bulk of C- substituents in the 4-
amino-1,2,4-triazoles reduced of the hemiaminal formation. Replacement of phenyl
substituents into the 2-pyridyl by contrast, result in an increased formation of
hemiaminal. The new obtained data suggesting that not only intermolecular O-H…Ntr
hydrogen bonds but also other factors must be contributing to the hemiaminal isolation.
It seems that the additional intramolecular hydrogen bonds and π-π interaction between
aryl substituent triazole rings are these factors. The presence of two different
substituents in the triazole ring significantly affects the behavior of hemiaminals (11,
12) and Schiff Bases (13-18) which in solution the rotation around the N-N axis can be
sufficiently restricted on the NMR time scale at room temperature.
Acknowledgments
The research was supported by Wroclaw Research Centre EIT+ under the
project “Biotechnologies and advanced medical technologies—BioMed” (POIG
01.01.02-02-003/08-00) financed from the European Regional Development Fund
(Operational Program Innovative Economy, 1.1.2). Calculations have been carried out
in Wroclaw Centre for Networking and Supercomputing.
Conflicts of Interest
The authors declare no conflict of interest.
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