New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[ 5,1-c][1,2,4] triazoles through regioselective alkylation of 1H-6-methyl-3-phenyl- 7-phenylazopyrazolo[5,1-c][1,2,4]triazoles

Article abstract of DOI:10.2478/s11532-011-0151-2

1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2aa-ad) were obtained by regioselective alkylation of 1H-6-methyl-3-phenyl-7- phenylazopyrazolo[5,1-c][1,2,4]triazoles (2a). 1H-1-Alkyl-6-methyl-3-phenyl-7- phenylazopyrazolo[5,1-c]

Full text of DOI:10.2478/s11532-011-0151-2

Cent. Eur. J. Chem. • 10(2) • 2012 • 373-379
DOI: 10.2478/s11532-011-0151-2
Central European Journal of Chemistry
New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazo-
pyrazolo[5,1-c][1,2,4]triazoles through
regioselective alkylation of 1H-6-methyl-3-phe-
nyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles
Research Article
Vasile-Nicolae Bercean1, Valentin Badea1*,
Călin Deleanu2,3, Alina Nicolescu2,3
1Department of Applied Chemistry and Engineering of Organic and Natural
Compounds, Faculty of Industrial Chemistry and Environmental Engineering,
“Politehnica” University Timişoara, RO-300001 Timişoara, Romania
2“Petru Poni” Institute of Macromolecular Chemistry
of the Romanian Academy, RO-700487 Iaşi, Romania
3“Costin D. Nenitescu” Centre of Organic Chemistry of the Romanian
Academy, RO-060023 Bucharest, Romania
Received 27 September 2011; Accepted 5 December 2011
Abstract:
1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2aa-ad) were obtained by regioselective alkylation
of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2a). 1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c]
[1,2,4]triazoles 2aa and 2ab were also prepared by coupling phenyldiazonium chloride with 1H-1-alkyl-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazoles 1aa and 1ab. The new compounds were characterized by IR, UV-VIS, 1H-NMR, 13C-NMR, and 15N-NMR
spectroscopy and their structures and actual tautomeric forms were established unequivocally.
Keywords: Pyrazolo[5,1-c][1,2,4]triazole • Regioselective N-alkylation • Azo compound • Tautomerism
© Versita Sp. z o.o.
1. Introduction
It was shown in our previous studies that the coupling
reaction of phenyldiazonium chloride with 1H-6-methyl-3-
Azomethinic and azo dyes derived from pyrazolo[5,1-c] phenylpyrazolo[5,1-c][1,2,4]triazole (1a) leads to the azo
[1,2,4]triazoles are key intermediates in the preparation dye 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c]
of photosensitive color materials, inks and toners [1-4], [1,2,4]triazole(2a)[16],whilethealkylationof1H-6-methyl-
and in other areas of interest [5-8]. The literature on the 3-phenylpyrazolo[5,1-c][1,2,4]- triazole (1a) and 1H-7-
subject of synthesis and properties of these compounds, ethoxycarbonyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]
except the patent literature, is, to our knowledge, rather triazole (3a) occurs regioselectively, with the formation
scarce.
of
1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]
There have been studies, described in the literature, triazoles (1aa-ab) and 1H-1-alkyl-7-ethoxycarbonyl-6-
on the annular tautomerism of pyrazoles [9-13] and methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazoles (3aa-ad),
1
aza-3a-pentalene systems containing 10 π electrons, respectively, as proven by H-NMR and 13C-NMR [17]
which include the pyrazolo[5,1-c][1,2,4]triazole system spectroscopy (Scheme 1).
[14,15], where it has been reported that one of the
tautomeric forms predominates, but to our knowledge alkylation
In this work we extended the study of the
reaction to 1H-6-methyl-3-phenyl-7-
there has been no research done on the nature of the phenylazopyrazolo[5,1-c][1,2,4]triazole (2a), employing
compounds formed in the functionalization reactions of 1H-NMR, 13C-NMR and 15N-NMR spectroscopy for
these tautomers.
the structure determination of the compounds formed
* E-mail: valentin.badea@chim.upt.ro
373

New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazo-
pyrazolo[5,1-c][1,2,4]triazoles through regioselective alkylation
of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles
using two alternative syntheses. Thus, in this study 2H, J11-H, 12-H = 7.2 Hz, J11-H, 13-H = 1.2 Hz, 11-H, 15-H),
the structure of the alkylation products and the actual 7.55-7.43 (m, 5H, 3′-H, 4′-H, 5′-H, 12-H, 14-H), 7.32 (tt,
tautomeric forms in which they exist were established 1H, J13-H, 14-H = 7.2 Hz, J13-H, 15-H = 1.2 Hz, 13-H), 4.41
unequivocally by 2D-NMR.
(s, 3H, 1-N-CH3), 2.74 (s, 3H, 6-C-CH3); δC (CDCl3, 100
MHz): 159.9 (6-C), 153.4 (10-C), 139.3 (3-C), 139.2
(7a-C), 130.4 (4′-C), 128.9 (12-C, 14-C), 128.8 (3′-C,
4′-C), 128.4 (13-C), 126.6 (2′-C, 6′-C), 125.1 (1′-C),
121.2 (11-C, 15-C), 118.2 (7-C), 39.8 (1-N-CH3), 13.1
2. Experimental procedure
The chemical reagents were purchased from (6-C-CH3); δN (CDCl3, 40 MHz): 286.2 (2-N), 254.2 (5-N),
commercial sources (Merck, Fluka) and used in 158.6 (1-N). Calcd. (%) for C18H16N6: C 68.34; H 5.10; N
syntheses with no further purification. 1H-6-Methyl-3- 26.56. Found (%): C 68.07; H 4.97; N 26.18.
phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazole (2a)
1 - E t h y l - 6 - m e t h y l - 3 - p h e n y l - 7 -
[16], 1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole phenylazopyrazolo[5,1-c][1,2,4]triazole (2ab). Yellow
(1a) [1], 1H-6-alkyl-6-methyl-3-phenylpyrazolo[5,1-c] powder. Yield 29%; m.p. 191-193°C. IR (KBr): 3450,
[1,2,4]triazoles (1aa-ab) [1] and 1H-7-ethoxycarbonyl- 3059, 3023, 2975, 2935, 1567, 1489, 1295, 1197, 1147,
6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole (3a) [1] 1072, 962, 763, 688 cm-1. UV-VIS: λmax (εmax x 104) =
were prepared by methods described in literature. The 380.0 nm (2.942). δH (CDCl3, 400 MHz): 8.38 (dt, 2H,
methods used for N-alkylation of pyrazolo[5,1-c][1,2,4] J2′-H, 3′-H = 8.2 Hz, J2′-H, 4′-H = 1.4 Hz, 2′-H, 6′-H), 7.72 (d,
triazoles are modifications of these used in N-alkylation 2H, J = 7.6 Hz, 11-H, 15-H), 7.51-7.40 (m, 5H, 3′-H, 4′-H,
of 1,2,4-triazole [18].
5’-H, 12-H, 14-H), 7.33-7.26 (m, 1H, 13-H), 4.81 (q, 2H,
The melting points were determined on a Böetius J = 7.0 Hz, -CH2CH3), 2.74 (s, 3H, 6-C-CH3), 1.51 (t, 3H,
PHMK apparatus (Veb Analytik Dresden). TLC was J = 7.0 Hz, -CH2CH3); δC (CDCl3, 100 MHz): 160.0 (6-C),
performed on 60 F254 Merck silica gel plates using 153.5 (10-C), 139.2 (3-C), 138.9 (7a-C), 130.4 (4′-C),
benzene-ethyl acetate 1:1 (v/v) as eluent. The IR spectra 128.9 (12-C, 14-C), 128.8 (3′-C, 5′-C), 128.4 (13-C),
were recorded in KBr pellets, using a Jasco FT/IR-410 126.6 (2′-C, 6′-C), 125.2 (1′-C), 121.2 (11-C, 15-C),
1
spectrometer. The H, 13C and 15N-NMR spectra were 118.5 (7-C), 47.9 (-CH2CH3), 16.3 (-CH2CH3), 13.1 (6-C-
recorded on a Bruker Avance DRX 400 (400 MHz for CH3); δN (CDCl3, 40 MHz): 284.1 (2-N), 254.3 (5-N),
1H, 100 MHz for 13C and 40 MHz for 15N) spectrometer, 173.7 (1-N). Calcd. (%) for C19H18N6: C 69.07; H 5.49; N
using TMS as internal reference.
25.44. Found (%): C 68.90; H 5.22; N 25.25.
2.2.
Preparation of 1H-1-alkyl-6-methyl-3-
phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]
triazoles (2aa-ad) through regioselective
alkylation of 1H-6-methyl-3-phenyl-7-
phenylazopyrazolo[5,1-c][1,2,4]triazole
(2a)
2.1.
Procedure for the preparation of
1H-1-alkyl-6-methyl-3-phenyl-7-
phenylazopyrazolo[5,1-c][1,2,4]triazoles
(2aa-ab) through azo coupling
The solution of diazonium salt prepared from aniline
(1 mmole) is added at 0-5°C to a solution of 1H-1-alkyl-
6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole
(1aa,
General procedure for the preparation of 1,6-
dimethyl-3-phenyl-7-phenylazopyrazolo[5,1-c]
[1,2,4]triazole (2aa) and 1-ethyl-6-methyl-3-phenyl-
7-phenylazopyrazolo[5,1-c][1,2,4]triazole
through alkylation of 1H-6-methyl-3-phenyl-7-
phenylazopyrazolo[5,1-c][1,2,4]triazole (2a) with
dimethyl sulfate and diethyl sulfate, respectively.
Me2SO4 and Et2SO4 (1.2 mL) were added at room
temperature to a solution of 1H-6-methyl-3-phenyl-7-
phenylazopyrazolo[5,1-c][1,2,4]triazole (2a) (0.6 and
0.33 mmoles, respectively) in NaOH 5% (3.0 and 1.5 mL,
respectively) and ethanol (10 and 5 mL, respectively),
and the mixture is stirred for 30 minutes. The reaction
mass is filtered, the precipitate is washed with water,
dried and recrystallized from ethanol.
1ab) (1 mmole) in ethyl alcohol (5 mL) and CH3COONa
(4 mmoles) in water (0.5 mL). The azo dye formed is
extracted with ethyl acetate (25 mL) and the organic
layer is washed successively with NaOH 2.5% (2×5 mL)
and water (5 mL). After drying on anhydrous Na2SO4,
decantation and removal of the solvent to dryness, the
chromatographically pure azo dyes are obtained.
1,6-Dimethyl-3-phenyl-7-phenylazopyrazolo[5,1-c]
[1,2,4]triazole (2aa). Dark yellow powder. Yield 55%;
m.p. 196-198°C. IR (KBr) νmax: 3462, 3060, 3029, 2931,
2872, 2823, 1572, 1491, 1452, 1415, 1378, 1242, 1182,
1073, 976, 764, 689 cm-1. UV-VIS: λmax (εmax x 104) =
379.6 nm (2.845). δH (CDCl3, 400 MHz): 8.39 (dt, 2H,
J2′-H, 3′-H = 7.2 Hz, J2′-H, 4′-H = 1.2 Hz, 2′-H, 6′-H), 7.75 (dd,
(2ab)
374

V. Bercean et al.
13
14
15
12
11
10
9 N
N
N
X
N8
7
N
R
R
N1
N
H
N
7a
N
N
N
ii, iii, iv, v
i
ii, iii, iv, v
H3C
H3C
H3C
2
H3C
N
N
N
6
N
N
N
N
N
N
5
N
N
4
3
1'
R
C6H5
2'
3'
C6H5
C6H5
6'
1aa-ab 3aa-ad
,
2aa-ad
2a
2ba-bd
5'
4'
1aa
1ab
), -C2H5 (
X=H; R=-CH3 (
)
1''
2''
3''
3''
2''
6''
2aa
X=-N=N-C6H5; R=-CH3 (
2ab
2ac
3ac
2ad
), -C2H5 (
), -CH2-CH=CH2 (
), -CH2-C6H5 (
3ad
), -CH2-C6H5 (
)
1''
4''
-H2C
3aa
3ab
X=-COOC2H5; R=-CH3 (
), -C2H5 (
), -CH2-CH=CH2 (
)
5''
i= C6H5N2]+Cl- / C2H5OH-H2O / NaOH
iii= (C H ) SO / DMF / NaOH
ii= (CH3)2SO4 / DMF / NaOH;
2
5 2
4
iv= CH2=CH-CH2Br / MEK / K2CO3;v= C6H5CH2Br / MEK / K2CO3
Scheme 1. The reaction conditions and the products obtained.
1,6-Dimethyl-3-phenyl-7-phenylazopyrazolo[5,1-c]
[1,2,4]triazole (2aa).Yellow powder.Yield 56%; m.p. 196-
198°C. The spectroscopic data are identical with those
of the same compound obtained previously through azo
coupling. Calcd. (%) for C18H16N6: C 68.34; H 5.10; N
26.56. Found (%): C 68.07; H 4.98; N 26.23.
1 - E t h y l - 6 - m e t h y l - 3 - p h e n y l - 7 -
phenylazopyrazolo[5,1-c][1,2,4]triazole (2ab). Yellow
powder. Yield 55%; m.p. 191-193°C. The spectroscopic
data are identical with those of the same compound
obtained previously through azo coupling. Calcd. (%) for
C19H18N6: C 69.07; H 5.49; N 25.44. Found (%): C 68.94;
H 5.36; N 25.22.
1 - A l l y l - 6 - m e t h y l - 3 - p h e n y l - 7 -
phenylazopyrazolo[5,1-c][1,2,4]triazole (2ac). Yellow
powder. Yield 98%; m.p. 89-92°C. IR (KBr): 3065, 3029,
2964, 2935, 2916, 2835, 1643, 1564, 1489, 1449, 1285,
1195, 1151, 765, 713, 689, 674 cm-1. UV-VIS λmax (εmax
x 104) = 379.2 (2.740). δH (CDCl3, 400 MHz): 8.41 (dt,
2H, J2′-H, 3′-H = 6.8 Hz, J2′-H, 4′-H = 1.6 Hz, 2′-H, 6′-H), 7.76
(dd, 2H, J11-H, 12-H = 8.4 Hz, J11-H, 13-H = 1.2 Hz, 11-H, 15-H),
7.56-7.44 (m, 5H, 3′-H, 4′-H, 5′-H, 12-H, 14-H), 7.33 (tt,
1H, J13-H, 14-H = 7.2, J13-H, 15-H = 1.2 Hz, 13-H), 6.90 (qt, 1H,
2.3. Preparationoftheazodye1-allyl-6-methyl-
3-phenyl-7-phenylazopyrazolo[5,1-c]
[1,2,4]triazole
(2ac)
through
alkylation of 1H-6-methyl-3-phenyl-7-
phenylazopyrazolo[5,1-c][1,2,4]triazole
(2a) with allyl bromide
To
a
suspension
of
1H-6-methyl-3-phenyl-7-
(2a)
phenylazopyrazolo[5,1-c][1,2,4]triazole
(0.33 mmoles) and allyl bromide (0.07 mL) in ethanol
(5 mL), a NaOH 5% solution (0.8 mL) is added at room
temperature, and the orange solution formed is kept
10 minutes at room temperature. The yellow suspension
formed is poured into water (25 mL) and then filtered.
The compound obtained is chromatographically pure.
2.4.
Preparation
of
the
azo
dye
1 - b e n z y l - 6 - m e t h y l - 3 - p h e n y l - 7 -
phenylazopyrazolo[5,1-c][1,2,4]triazole
(2ad) through alkylation of 1H-6-methyl-3-
phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]
triazole (2a) with benzyl chloride
To a solution of benzyl chloride (0.091 mL) and KI
J
2”-H, 3”-Hb = 17.2 Hz, J2”-H, 3”-Ha = 10.4 Hz, J2”-H, 1”-H = 5.6 Hz,
2”-H), 5.45 (dt, 2H, J1”-H, 2”-H = 5.6 Hz, J1”-H, 3”-H = 1.2 Hz,
2x1”-H), 5.28 (dd, 1H, J3”-Hb, 2′′-H = 17.2 Hz, J3”-Hb, 3′′-Ha
(0.06 g) in
K2CO3 (0.109 g)
7-phenylazopyrazolo[5,1-c][1,2,4]triazole
acetone (15 mL), finely powdered
and 1H-6-methyl-3-phenyl-
(2a)
=
1.2 Hz, 3”-Hb), 5.23 (dd, 1H, J3”-Ha, 2”-H = 10.4 Hz, J3”-Ha,
(0.33 mmoles) are added at 50°C. After refluxing
for 2 hours, the yellow-reddish suspension formed
is cooled, filtered and the precipitate is washed with
acetone. After removing the solvent under low pressure,
compound 2ad is obtained chromatographically pure.
= 1.2 Hz, 3”-Ha), 2.76 (s, 3H, 6-C-CH3); δC (CDCl3,
3”-Hb
100 MHz): 160.0 (6-C), 153.5 (10-C), 139.8 (3-C), 139.0
(7a-C), 133.1 (2”-C), 130.5 (4′-C), 129.0 (12-C, 14-C);
128.8 (3′-C, 5′-C), 128.5 (13-C), 126.8 (2′-C, 6′-C), 125.1
(1′-C), 121.2 (11-C, 15-C), 118.5 (3”-C), 118.3 (7-C),
375

New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazo-
pyrazolo[5,1-c][1,2,4]triazoles through regioselective alkylation
of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles
54.6 (1”-C), 13.1 (6-C-CH3); δN (CDCl3, 40 MHz): 284.6
(2-N), 255.2 (5-N), 169.6 (1-N). Calcd. (%) for C20H18N6:
C 70.16; H 5.30; N 24.54. Found (%): C 70.15; H 5.10;
N 24.29.
1 - B e n z y l - 6 - m e t h y l - 3 - p h e n y l - 7 -
phenylazopyrazolo[5,1-c][1,2,4]triazole (2ad). Light
yellow powder. Yield 77%; m.p. 146-149°C. IR (KBr):
3153, 3054, 3029, 2979, 2937, 2898, 2878, 1563, 1488,
1451, 1263, 1192, 1153, 978, 770, 689 cm-1. UV-VIS λmax
(εmax x 104) = 380 (3.053). δH (CDCl3, 400 MHz): 8.44 (d,
X
X
7
R
N1
N
7a
N
H3C
N
H3C
2
N
6
N
N
N
4
3
5
1'
R
2'
3'
6'
5'
4'
1b, 2b, 3b
1a, 2a, 3a
X= H,
R= H (1a, 1b)
2H, J2′-H, 3′-H = 6.8 Hz, 2′-H, 6′-H), 7.81 (d, 2H, J11-H, 12-H
=
X= N=N-C6H5, R= H (2a, 2b)
X= COOC2H5, R= H (3a, 3b)
7.6 Hz, 11-H, 15-H), 7.58-7.46 (m, 7H, 3′-H, 4′-H, 5′-H,
2”-H, 6”-H 12-H, 14-H), 7.40-7.30 (m, 4H, 13-H, 3”-H,
4”-H, 5”-H), 6.08 (s, 2H, -CH2-Ph), 2.82 (s, 3H, 6-C-
CH3); δC (CDCl3, 100 MHz): 150.2 (6-C), 153.4 (10-C),
139.9 (3-C), 138.7 (7a-C), 136.5 (1”-C), 130.5 (4′-C),
129.0 (12-C, 14-C), 128.8 (3′-C, 5′-C), 128.7 (3”-C,
5”-C), 128.5 (13-C), 128.2 (2”-C, 6”-C), 128.0 (4”-C),
126.8 (2′-C, 6′-C), 125.2 (1′-C), 121.2 (11-C, 15-C),
118.2 (7-C), 55.5 (-CH2-Ph), 13.1 (6-C-CH3); δN (CDCl3,
40 MHz): 284.8 (2-N), 255.6 (5-N), 172.1 (1-N). Calcd.
(%) for C24H20N6: C 73.45; H 5.14; N 21.41. Found (%):
C 73.21; H 5.04; N 21.14.
Figure 1. Tautomeric forms in the 3,6-di- and 3,6,7-trisubstituted
pyrazolo[5,1-c][1,2,4]triazole system.
6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole
(1)
1
the direct coupling J between the nitrogen atom at
153.7 ppm and the proton at 12.94 ppm can be observed,
whichindicatesthattheprotonat12.94ppmiseither1-N-H
(1a) or 5-N-H (1b). The nitrogen atom at 252.3 ppm long-
range couples with the protons at 2.34 ppm (6-C-CH3).
The only nitrogen atom that is able to long-range couple
(3J) with the 6-C-CH3 protons is the 5-N atom, because
all the other nitrogen atoms are located at distances
longer than three bonds. Therefore the nitrogen atom at
252.3 ppm is the 5-N atom. Since no direct coupling
between the 5-N atom and any proton is observed,
the only direct coupling being between the nitrogen at
153.7 ppm and the proton at 12.94 ppm, and since the
nitrogen at 153.7 ppm does not couple with the 6-C-CH3
protons,we can conclude that the nitrogen at 153.7 ppm
is 1-N. From the above spectroscopic observations one
can draw a conclusion that the tautomeric form in which
compound 1 exists is 1a, not 1b.
3. Results and discussion
Theoretically,
[1,2,4]triazole
1H-6-methyl-3-phenyl-pyrazolo[5,1-c]
(1), 1H-6-methyl-3-phenyl-7-
phenylazopyrazolo[5,1-c][1,2,4]triazole (2) and 1H-7-
ethoxycarbonyl-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]
triazole (3) can exist as two tautomeric forms a and b
(Fig. 1): a 1H-tautomeric form (a), in which the hydrogen
is bonded to the nitrogen in position 1 (1-N), and a 5H-
tautomeric form (b), in which the hydrogen is bonded to
the nitrogen in position 5 (5-N).
Based on the analysis of the 2D 1H-15N NMR
spectra recorded, we can affirm that 6-methyl-3-
phenylpyrazolo[5,1-c][1,2,4]triazole (1), 6-methyl-3-
1
In the 2D HMBC H-15N spectrum of compound 1a,
the long-range couplings between the nitrogen atom
at 225.9 ppm and the protons 1-N-H at 12.94 ppm
and 7-C-H at 5.69 ppm, respectively, are observed.
The only nitrogen atom that can simultaneously long-
range couple (3J) with these protons is the 4-N nitrogen.
Also, the vicinal coupling between the nitrogen at
276.3 ppm and the 1-N-H proton at 12.94 ppm is
observed, a coupling (2J) possible only for the 2-N
nitrogen.
phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazole
(2)
and 7-ethoxycarbonyl-6-methyl-3-phenylpyrazolo[5,1-c]
[1,2,4]triazole (3) exist only as 1H-tautomeric forms
(a), a fact that explains their regioselective alkylation
occurring exclusively at the 1-N nitrogen.
In the 2D HMBC 1H-13C spectrum of compound
2
2
2
3
Thus, in the 2D HMBC 1H-15N spectrum of 6-methyl-
3-phenylpyrazolo[5,1-c][1,2,4]triazole (1) the long-
range couplings between the four nitrogen atoms
of the pyrazolo-triazole system and three different
protons is observed: one at 12.94 ppm (N-H), one at
5.69 ppm (7-C-H) and one at 2.34 ppm (6-C-CH3). The
signals of the four nitrogen atoms in this heterocyclic
system appear at 153.7, 225.9, 252.3 and 276.3 ppm,
1a the J7a-C, 1-N-H, J7a-C, 7-C-H, J6-C, 6-C-CH3, J7-C, 6-C-CH3 and
3J3-C,
long-range couplings are also observed. In
1-N-H
conclusion, in conformity with the above-presented
spectroscopic data, we can state with certainty that 1H-
6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]triazole 1 exist
as the tautomeric form 1a, and the four nitrogen atoms
in the heterocycle appear at the following values: 1-N
at 153.7 ppm, 2-N at 276.3 ppm, 4-N at 225.9 ppm and
5-N at 276.3 ppm.
1
respectively. In the 2D HMQC H-15N spectrum of 1H-
376

V. Bercean et al.
The elucidation of the structure of compound 1a
was necessary, because in the case of compound 2a
1
no signal for the 1-N-H proton appears in the H-NMR
spectrum, even though various solvents were employed
(DMSO-d6, CDCl3, C6D6 and CD3CN) and the studies
were conducted at low temperature (-30°C in CDCl3
and CD3CN). Due to the absence of the signal for the
1-N-H proton, there are no signals for the 1-N, 2-N
N
H
N
N
N
H3C
N
1
and 4-N nitrogen atoms in the 2D HMBC H-15N-NMR
N
1
spectrum, because of the lack of the J1-N, 1-N-H direct
2
3
coupling and the J2-N,
and J4-N,
long-range
1-N-H
1-N-H
couplings. Only the signal for the 5-N nitrogen atom
appears at 256.9 ppm, due to the long-range coupling
with the 6-C-CH3 protons (3J5-N, 6-C-CH3). The absence of
the signal for the 1-N-H proton was also observed for
Formation of an intermolecular hydrogen bond in
1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]
triazole compounds.
Figure 2.
other previously synthesized 1H-7-arylazo-6-methyl- previous assignments of the signals corresponding to
3-phenylpyrazolo[5,1-c][1,2,4]triazole derivatives the nitrogen atoms in compounds 1a and 3a, and the
variously substituted on the aryl ring [16]. It is interesting fact that the only nitrogen atom in compound 2aa able
that, in the case of 1H-7-ethoxycarbonyl-6-methyl-3- to long-range couple (3J) with the 6-C-CH3 protons is the
phenylpyrazolo[5,1-c][1,2,4] triazole (3a), the signal for 5-N nitrogen atom, we can safely assign the signal at
1
the 1-N-H proton exists and appears in the H-NMR 254.2 ppm to this atom. Similarly, in agreement with the
spectrum at 13.95 ppm in DMSO-d6, and therefore the attributions previously made for compounds 1a and 3a,
four nitrogen atoms could be identified based on their the other two nitrogen atoms that can long-range couple
direct and long-range couplings at 163.6 ppm (1-N), (2J and 3J) with the protons of the N-CH3 group are the
222.8 ppm (4-N), 257.7 ppm (5-N) and 278.3 ppm (2-N). 1-N atom at 158.6 ppm and the 2-N atom at 286.2 ppm,
A possible explanation for the absence of the signal of respectively.
the 1-N-H proton in the case of 1H-7-arylazo-6-methyl-
Based on the absence of the coupling (2J) between
3-phenylpyrazolo[5,1-c][1,2,4] triazole compounds could the 5-N nitrogen atom and the methyl group, introduced
be the formation of intermolecular hydrogen bonds in through alkylation, at 4.41 ppm (N-CH3), we can
a six-atom ring between the 1-N-H proton and the azo conclude that the alkylation of 1H-6-methyl-3-phenyl-
nitrogen atom attached to the aryl ring, as shown in 7-phenylazopyrazolo[5,1-c][1,2,4]triazole (1) occurs
Fig. 2. The intermolecular hydrogen bond formed can regioselectively, exclusively at the 1-N nitrogen atom,
lead to a rapid proton exchange between the two nitrogen and the alkylated compound obtained exists only as the
atoms (the heterocyclic and the azo), which causes the 1H-1-methyl isomer (2aa).
proton’s decoupling from the 1-N nitrogen atom and
renders its coupling with this atom unobservable.
Another argument in favor of the 1H-1-methyl isomer
(2aa) is the existence in the 2D-HMBC 1H-13C spectrum
For the two analyzed compounds 1a and 3a it can of the long-range coupling (3J) between the 7a-C carbon
1
be observed in the 2D-HMBC H-15N spectra that the atom and the methyl protons at 4.41 ppm, a coupling
shielding of nitrogen atoms in the pyrazolo-triazole which wouldn’t be possible if the alkylation occurred at
system decreases in the order 1-N > 4-N > 5-N > 2-N; the 5-N nitrogen atom, since it would be a four-bond
thus the most shielded nitrogen atom is 1-N, while the coupling (4J).
least shielded is 2-N.
Also, in the case that the alkylation had occurred
In the 2D-HMBC 1H-15N spectrum of 1,6-dimethyl-3- on the tautomeric form 2b, at the 5-N nitrogen atom,
phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazole (2aa), maximumtwolong-rangecouplingsbetweenthenitrogen
there are long-range couplings observed between atoms and protons would have been observed in the
1
the three nitrogen atoms at 158.6 ppm, 254.2 ppm 2D-HMBC H-15N spectrum of the alkylated compound,
and 286.2 ppm, and two types of protons, the ones at that is for the 5-N and 4-N nitrogen atoms, because the
4.41 ppm assigned to the 1-N-CH3 methyl group and couplings for the 2-N and 1-N atoms, respectively, are
those at 2.74 ppm assigned to the 6-C-CH3 methyl group. impossible to observe, as they are over distances longer
The nitrogen atoms at 158.6 ppm and 286.2 ppm couple than three bonds.
with the methyl protons at 4.41 ppm (1-N-CH3), while
Similarly to the 2D-HMBC 1H-15N spectrum
the nitrogen atom at 254.2 ppm couples with the methyl of the N-methylated compound 2aa, in the spectra of
protons at 2.74 ppm (6-C-CH3). Taking into account the N-ethylated 2ab, N-allylated 2ac and N-benzylated 2ad
377

New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazo-
pyrazolo[5,1-c][1,2,4]triazoles through regioselective alkylation
of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles
compounds long-range couplings are observed between well-known in the literature for a long time, each time
three nitrogen atoms and the following protons: that of they are presented exclusively as the tautomeric form
the 1-N and 2-N atoms with the 1-N-CH2- methylene 1a, without providing any scientific reason for this. In this
protons and that of the 5-N atom with the 6-C-CH3 study we elucidated the structure of these compounds
1
1
methyl protons.
using 2D H-15N-NMR and H-13C-NMR spectroscopy,
In the 2D-HMBC 1H-13C spectra of the three above- clearly showing that they exist solely as the tautomeric
mentioned compounds (2ab, 2ac and 2ad), the long- form 1a and 3a, respectively. Also, for the first time, the
range couplings between the 7a-C carbon and the 1-N- corresponding chemical shifts were assigned to the four
CH2- methylene groups are also observed.
heterocyclic nitrogen atoms in these two compounds,
Interpretation of the NMR spectroscopic data for based on the 2D 1H-15N-NMR spectra.
the N-ethyl (2ab), N-allyl (2ac) and N-benzyl (2ad)
It was demonstrated that the monoalkylation of 1H-
compounds, respectively, using the same reasoning as 6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]
for the N-methyl compound (2aa), certifies that in these triazole (2a) with various alkylating agents occurs
cases the alkylation also occurred regioselectively and regioselectively, yielding 1-N-alkylated compounds
1
exclusively at the 1-N nitrogen atom, in agreement with 2aa-ad, as proved through 2D HMBC H-15N-NMR and
the tautomeric form 2a.
Two of these
1H-13C-NMR spectroscopy and through comparison of
1H-1-alkyl-6-methyl-3-phenyl- their identity with compounds 2aa and 2ab obtained
7-phenylazopyrazolo[5,1-c][1,2,4]triazole
2aa and 2ab, were also prepared by coupling with
dyes, alternatively by the coupling of phenyldiazonium chloride
1H-1-alkyl-6-methyl-3-phenylpyrazolo[5,1-c]
phenyldiazonium chloride with 1H-1-alkyl-6-methyl- [1,2,4]triazoles 1aa and 1ab. Also, the chemical shifts
3-phenyl-pyrazolo[5,1-c][1,2,4]triazoles 1aa and 1ab, corresponding to the heterocyclic nitrogen atoms in the
respectively, using the method described in literature alkylated compounds were attributed, based on the
[9]. Their identity with the compounds 2aa and 2ab long-range couplings with protons observed in the 2D
obtained through the alkylation of 1H-6-methyl-3-phenyl- 1H-15N-NMR spectra.
7-phenylazopyrazolo[5,1-c][1,2,4]triazole (2a) was
established by comparing their physical characteristics
and using IR, UV-VIS, 1H-NMR, 13C-NMR and 15N-NMR
spectroscopy.
4. Conclusions
Although
1H-6-methyl-3-phenylpyrazolo[5,1-c][1,2,4]
triazole (1a) and 1H-7-ethoxycarbonyl-6-methyl-3-
phenylpyrazolo[5,1-c][1,2,4]triazole (3a) have been
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