Regioselective alkylation of 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole

Article abstract of DOI:10.1016/j.tet.2006.11.067

Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole using different alkylating agents leads regioselectively to 1-N-alkylated products. The hydrolysis-decarboxylation o

Full text of DOI:10.1016/j.tet.2006.11.067

Tetrahedron 63 (2007) 1467–1473
Regioselective alkylation of 1H-7-ethoxycarbonyl-
6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and
1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole
a
b
a
Valentin Badea,a, Maria D. Sxofei, Monica M. Venter and Vasile N. Bercean
*
a‘Politehnica’ University Timixsoara, Faculty of Industrial Chemistry and Environment Engineering,
Carol Telbisz 6, RO-300006 Timixsoara, Romania
b‘Babexs-Bolyai’ University Cluj-Napoca, Faculty of Chemistry and Chemical Engineering,
Arany Janos 11, RO-400028 Cluj-Napoca, Romania
Received 2 August 2006; revised 7 November 2006; accepted 23 November 2006
Available online 20 December 2006
Abstract—Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo-
[5,1-c][1,2,4]triazole using different alkylating agents leads regioselectively to 1-N-alkylated products. The hydrolysis–decarboxylation of
1,6-dimethyl-7-ethoxycarbonyl-pyrazolo[5,1-c][1,2,4]triazole yields a compound identical with that obtained by the direct methylation of
1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole. The 1-N-alkylation is confirmed by NMR spectroscopy and mass spectrometry.
Ó 2006 Elsevier Ltd. All rights reserved.
X
X
7
H
H
1. Introduction
1
X
7a
N
N
N
6
2
H3C
H3C
N
N
3
H3C
N
The interest for pyrazolo[5,1-c][1,2,4]triazole derivatives
relies on their industrial applications, such as precursors for
photosensitive materials (i.e., inks and toners)1–5 and ingre-
dients in cosmetics.6,7 To the best of our knowledge, the prop-
erties of the title class of compounds have been poorly
investigated so far. There are very few scientific papers deal-
ing with this topic and none of them reports on the alkylation
reactions of such derivatives. As a result, we became inter-
ested in the preparation9,12,14 and properties8,9–11,13–15 of
the heterocyclic pyrazolo[5,1-c][1,2,4]triazole systems. For
example, one of our previous reports established that the
acetylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]-
triazole 1 leads mainly to the monoacetylated product 5a
mixedwith very smallamount of the 5b isomer (Scheme 1).10
N
N
N
N
H
N
5
N
4
1'
C6H5
2'
3'
C6H5
(1c,2c)
(1a,2a) 6'
(1b,2b)
5'
4'
N
R
X
X
X
R
N
N
N
N
H3C
N
H3C
H3C
N
N
N
N
N
R
N
C6H5
C6H5
C6H5
(3a,4a,5a)
(3c,4c)
(3b,4b,5b)
1a-c,3a-c,5a,5b X=H 2a-c,4a-c X= -COOC2H5 3a-c,4a-c R=alkyl
5a,5b R=CH3CO
Scheme 1. Possible alkylation and acylation pathways of the heterocyclic
pyrazolo[5,1-c][1,2,4]triazole system.
The aim of this work is to study the alkylation reaction of
3,6-disubstituted and 3,6,7-trisubstituted pyrazolo[5,1-c]-
[1,2,4]triazole systems as well as 1H-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazole 1 and 1H-7-ethoxycarbonyl-
6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole 2.
2. Results and discussion
In a similar fashion to the acetylation process, the monoalkyl-
ation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]tri-
azole 1, which can exist in three tautomeric forms 1a–c,
might lead theoretically to the corresponding isomeric
products 3a–c (Scheme 1). Furthermore, the monoalkylation
of 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c]-
[1,2,4]triazole 2, which may also exist in three tautomeric
forms 2a–c, could lead theoretically to the corresponding
isomers 4a–c (Scheme 1).
Keywords: Pyrazolo[5,1-c][1,2,4]triazoles; N-Alkylation; Hydrolysis–
decarboxylation.
* Corresponding author. Tel.: +40 742 044969; e-mail: valentin.badea@
chim.upt.ro
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.067

1468
V. Badea et al. / Tetrahedron 63 (2007) 1467–1473
X
R
X
H
1
1
7
7a
7
7a
N
N
6
6
2
2
N
H3C
H3C
N
3
N
N
3
N
i-vi
N
4
4
5
5
1'
1'
2'
3'
2'
3'
6'
6'
(6a-15a)
5'
(1a,2a)
5'
4'
4'
i=R2SO4 / NaOH / DMF (6a,7a); ii=RBr / NaOH / DMF (6a-8a);
iii=RBr / K2CO3 / KI / MEK (8a-12a); iv=(CH3)2SO4 / NaOH 5% or CH3I / K2CO3 / MEK (13a);
v=RBr / C2H5ONa / C2H5OH (14a); vi=ClCH2COOH / NaOH 5% (15a)
6a
7a
8a
9a
10a
11a
X
R
COOC2H5 COOC2H5 COOC2H5
H2
COOC2H5
COOC2H5
COOC2H5
2"
3"
H12
H11
C2H5
CH3
1"
CH(CH3)COOCH3
C
CH2COOC2H5
9
4"
H2C
10H
5"
6"
Yield
(%)
75
92
86.5
91
31
45
12a
COOC2H5
CH(C2H5)CHCOOCH3 CH3 CH2COOC2H5
30 68 40
13a
14a
15a
16a
17a
X
R
H
H
H
H
C2H5
76
H
CH2COOH
CH2C6H5
90
Yield
(%)
48
Scheme 2. Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole 1 and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole 2.
The alkylation process of the pyrazolo-triazole systems was
studied following the transformation of 1 into 3a–c by meth-
ylation, transformation of 2 into 4a–c by methylation, ethyl-
ation, allylation and benzylation (Scheme 2), as well as by
the hydrolysis–decarboxylation of the 1-N-alkylated prod-
ucts (6a, 7a and 9a) (Scheme 3). In addition, the alkylation
of 1 and 2 with esters of a-halogeno-alkanoic acids was per-
formed (Scheme 2).
In order to elucidate the position where the alkylation takes
place, the products 6a and 7a were investigated by 2-D NMR
spectroscopy: 1H–1H COSY, 1H–13C COSY, HETCOR
(HMQC) and 1H–13C HMBC. The 1H–13C HMBC spectrum
3
of the N-methylated product 7a shows the J7a-C; 1-NꢀCH
3
coupling between the 7a-C carbon atom and the protons of
the N–CH3 unit. Such a coupling is possible only if the alkyl-
ation takes place at the 1-N nitrogen atom.
Alternatively, if the alkylation took place at the 5-N nitrogen
atom, the coupling distance would be much larger and the
O
O
H
7
R
1
R
1
coupling would not be noticeable in the H–13C HMBC
7a
N
N
H2SO4 80% / CH3COOH (2:8 v/v)
3
2
spectrum. Moreover, the
could support the 5-N-alkylation is absent. Other proton–
J
coupling, which
N
3
H3C
N
H3C
6-C; 5-NꢀCH3
6
N
N
130-140 °C
N
N
4
5
1'
carbon couplings noticed in the H–13C HMBC spectrum
1
2'
3'
6'
2
of 7a can be mentioned as follows: J
2J6-C; 6-CꢀCH
,
,
,
ꢀOCH2CH3; ꢀOCH2CH3
2 3
(13a,16a,17a)
(6a,7a,9a)
2J
,
,
3JC]O; OCH CH
5'
4'
ꢀOCH2CH3; ꢀOCH2CH3
3
3
3
3
3J7-C; 6-CꢀCH
,
J3-C; 2 ;6 -H
,
J4 -C; 2 ;6 -H
,
J2 ð6 Þ-C; 6 ð2 Þ-H
0
0
0
0
0
0
0
0
0
33
Scheme 3. Preparation of 1-alkyl-6-methyl-3-phenyl-pyrazolo[5,1-c]-
[1,2,4]triazoles (13a, 16a and 17a) by the hydrolysis–decarboxylation of
1-alkyl-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazoles
(6a, 7a and 9a).
3J2 ;6 -C; 4 -H, J1 -C; 3 ;5 -H, and 3J3 ð5 Þ-C; 5 ð3 Þ-H:
0
0
0
0
0
0
0
0
0
0
The ethylation reaction also yields the 1-N-alkyl iso-
mer 6a, which is supported by the assignment of the
3J7a-C; 1-NꢀCH ꢀCH coupling, as well as by the absence of
The ethylation and methylation of 2 were performed by
reacting the title compound with diethylsulfate and dime-
thylsulfate, respectively, in dimethylformamide (DMF) and
excess NaOH. In both cases, the syntheses yielded a single
isomer, the 1-N-ethylated 6a and 1-N-methylated 7a, respec-
tively, in very good yields (Scheme 2).
2
3
the J6-C; 5-NꢀCH ꢀCH coupling in the 1H–13C HMBC
3
2
3
spectrum. In addition, the spectrum shows couplings simi-
lar to compound 7a, except 2J
; and
ꢀNCH2CH3; ꢀNCH2CH3
2J
assigned to the ethyl group.
ꢀNCH2CH3; ꢀNCH2CH3
The ethylation and methylation of 2 with alkyl halides (ethyl
bromide and methyl iodide, respectively) in DMF and excess
NaOH led to the same 1-N-ethylated 6a and 1-N-methylated
7a products (Scheme 2). The N-allylation and N-benzylation
of 2 were performed following similar procedures.
The monoethylation and monomethylation were confirmed
by mass spectrometry. The mass spectra of 6a and 7a
show the molecular peaks at 298.06 and 284.17 amu, respec-
tively. These peaks also show the highest amplitude suggest-
ing that the molecular ions are easily generated and/or
are very stable. Moreover, the molecular fragmentation
of the title products is characteristic of the aromatic
The alkylation of 2 with allyl bromide in DMF and
excess NaOH occurred with very low yield (w2%). On the
other hand, 1-allyl-7-ethoxycarbonyl-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazole 8a was obtained successfully
+
ꢁ
esters M ꢀ OC2H5 and the McLafferty type transposition
M–CH2]CH2.

V. Badea et al. / Tetrahedron 63 (2007) 1467–1473
1469
by reacting the same starting materials in methyl ethyl
ketone (butanone, MEK) in the presence of K2CO3 and KI.
The alkylation of the 1-N atom is supported by the presence
130–140 ꢂC in an 80% H2SO4/CH3COOH (2:8 v/v) mixture.
The reaction yielded 1-alkyl-3-phenyl-6-methyl-pyrazolo-
[5,1-c][1,2,4]triazoles (Scheme 3). Compound 13a prepared
by this route is identical with that obtained by the N-alkyl-
ation of 1 with dimethylsulfate or methyl iodide. 1-Ethyl-
6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole (16a) and
1-benzyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole
(17a) were prepared in a similar manner. The mass
spectrum of 17a shows the base peak at 91 amu assigned
3
of the J7a-C; 1-NꢀCH ꢀCH]CH coupling and the absence
2
2
of the J6-C; 5-NꢀCH ꢀCH¼CH coupling in the 1H–13C
HMBC spectrum of 8a. In addition, the spectrum shows
3
2
2
couplings similar to the previous derivatives, except
2
2J9-C; 1-NꢀCH ꢀCH¼CH ; J10-C; 9-H and 2J11;12-C; 9-H charac-
2
2
teristic to the allyl group (Scheme 2). The H–1H COSY
spectrum reveals the J10-H, 9,11,12-H couplings of the allyl
protons.
1
+
to the tropylium cation (C7H7 ), as expected for benzyl
derivatives.
1-Benzyl-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo-
[5,1-c][1,2,4]triazole 9a was prepared by the reaction of 2
with benzyl bromide, in good yields (Scheme 2). The mass
spectrum of 9a reveals the fragmentation of the molecular
3. Conclusions
The monoalkylation of 1H-7-ethoxycarbonyl-6-methyl-3-
phenyl-pyrazolo[5,1-c][1,2,4]triazole 2 with dimethyl- and
diethylsulfate, and methyl, ethyl, allyl and benzyl halides,
or esters of a-halogeno-alkanoic acids in alkaline media
leads to the 1-N-alkylated derivative in each case.
+
ꢁ
ion by the release of the benzyl radical, M ꢀ CH2C6H5,
+
and the formation of the tropylium ion (C7H7 , 91 amu).
The latter ion was also assigned as the base peak, as expected
for benzyl derivatives.
The monoalkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c]-
[1,2,4]triazole 1 with methyl iodide or dimethylsulfate in
alkaline media leads to the same 1-N-methyl homologue.
Compounds 10a–12a were prepared by the alkylation of 2
with alkyl a-halogeno-alkanoic esters in MEK, in the pres-
ence of K2CO3 and KI (Scheme 2). In the case of compound
10a, the alkylation was performed with ethyl 2-bromoace-
The hydrolysis–decarboxylation of 1-alkyl-7-ethoxycar-
bonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole
derivatives (alkyl¼methyl, ethyl or benzyl) yields 1-alkyl-6-
methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazoles. In the case
of R¼methyl, the product is identical with that obtained by
direct methylation of 1.
3
tate and it is supported by the assignment of J7a-C; 1-Nꢀ
3
and the absence of
J
CH2ꢀCOOC2H5
6-C; 5-NꢀCH2ꢀCOOC2H5
couplings in the H–13C HMBC spectrum. In addition, the
1
2
spectrum reveals the
J
1-NꢀCH2ꢀCOOC2H5; 1-NꢀCH2ꢀCOOC2H5
and 3J1-NꢀCH ꢀCOOCH H ; 1-NꢀCH ꢀCOOCH CH
along with those common for the entire range of derivatives.
couplings,
2
2
3
2
2
3
The alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-
c][1,2,4]triazole (1) with dimethylsulfate in 5% NaOH solu-
tion or with methyl iodide in MEK, in the presence of K2CO3
and KI, yielded the N-alkylated homologue 1,6-dimethyl-3-
phenyl-pyrazolo[5,1-c][1,2,4]triazole (13a) (Scheme 2).
The fact that the 7-C atom was not alkylated is supported
by the assignment of d(7-C–H) at 5.72 ppm in the 1H
NMR spectrum.
4. Experimental
4.1. General
The chemical reagents were purchased from commercial
sources (Merck, Fluka) and used in syntheses with no further
purification. 1H-6-Methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]-
triazole 1 and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazole 2 were prepared by literature
methods.1 The preparation methods used for the N-alkyl-
ation of pyrazolo-triazoles are the modifications of the
N-alkylation of 1,2,4-triazole16 and benzimidazole.17
The alkylation of 1 with ethyl 2-bromoacetate in C2H5ONa/
C2H5OH yielded the N-alkylated product 1-(ethoxycar-
bonyl-methyl)-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]-
triazole (14a) (Scheme 2). Similar to the previous case, the
1H NMR spectrum of 14a shows d(7-C–H) at 5.75 ppm. In
addition, the mass spectrum of the title compound shows
the molecular peak at M¼284 amu.
€
The melting points were determined on a Boetius PHMK ap-
paratus (Veb Analytik Dresden). TLC was performed on 60
F254 Merck silica gel plates using benzene/ethyl acetate¼1:1
(v/v) as eluent. The IR spectra were recorded as KBr pellets,
using a Jasco FT/IR-410 spectrometer. The 1H and 13C NMR
spectra were recorded on Bruker DRX 400 (400 MHz for 1H
and 100 MHz for 13C), Varian Gemini 300 (300 MHz for 1H
and 75 MHz for 13C) or Bruker AC 200 (200 MHz for 1H and
50 MHz for 13C) spectrometer, using TMS as an internal ref-
erence. The mass spectra were recorded on a Varian FINNI-
GAN MAT 212 instrument at 54 eV.
The alkylation of 1 with chloroacetic acid in 5% NaOH
solution, at pH¼8–9, yielded the N-alkylated product 1-(car-
boxy-methyl)-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]tri-
azole (15a) (Scheme 2). The N-alkylation is supported by
1
the assignment of d(7-C–H) at 5.75 ppm in the H NMR
3
spectrum, as well as by the presence of J7a-C; 1-NꢀCH ꢀ
2
3
coupling and the absence of J6-C; 5-NꢀCH ꢀCOOH
COOH
2
coupling in the 1H–13C HMBC spectrum of 15a. The mass
spectrum of the product reveals the molecular fragmentation
typical to carboxylic acids, M+ꢀ45 (M+ꢀCOOH).
4.2. Alkylation of 1H-7-ethoxycarbonyl-6-methyl-3-
phenyl-pyrazolo[5,1-c][1,2,4] triazole (2)
1-Alkyl-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c]-
[1,2,4]triazole derivatives were subjected to single-step
hydrolysis–decarboxylation processes by heating them to
4.2.1. 7-Ethoxycarbonyl-1-ethyl-6-methyl-3-phenyl-pyr-
azolo[5,1-c][1,2,4]triazole (6a). Alkylation with diethylsul-
fate in NaOH/DMF: 0.675 g (2.5 mmol) of 2 and 0.36 mL

1470
V. Badea et al. / Tetrahedron 63 (2007) 1467–1473
(2.75 mmol) of Et2SO4 were added to a solution of 0.4 g
(10 mmol) of NaOH in 10 mL DMF under continuous stir-
ring. After stirring for 1 h, the product was precipitated in
20–30 mL distilled water and filtered.
with the product prepared by the previous method (TLC,
IR, NMR and MS).
4.2.3. 1-Allyl-7-ethoxycarbonyl-6-methyl-3-phenyl-pyra-
zolo[5,1-c][1,2,4]triazole (8a). Alkylation with allyl bro-
mide in NaOH/DMF: 0.1 g (0.37 mmol) of 2 and
0.058 mL (0.67 mmol) of allyl bromidewere added to a solu-
tion of 0.1 g (2.5 mmol) of NaOH in 5 mL DMF under con-
tinuous stirring. After stirring for 1 h, the product was
precipitated in 20 mL distilled water and filtered. Yield:
0.002 g of white powder (2%).
Yield: 0.566 g of white powder, 75%; mp: 112–114 ꢂC
(n-hexane); IR (KBr) nmax: 3060, 2978, 2933, 2910, 1679,
1598, 1489, 761, 688 cmꢀ1; dH (CDCl3, 400 MHz): 8.38–
8.36 (m, 2H, 20-H, 60-H), 7.53–7.43 (m, 3H, 30-H, 50-H, 40-
H), 4.66 (q, 2H, J¼7.1 Hz, –N–CH2CH3), 4.33 (q, 2H,
J¼7.1 Hz, –O–CH2CH3), 2.61 (s, 3H, 6-C–CH3), 1.50 (t,
3H, J¼7.1 Hz, 1-N–CH2CH3), 1.39 (t, 3H, J¼7.1 Hz, –O–
CH2CH3); dC (CDCl3, 100 MHz): 163.2 (C]O), 160.9 (6-
C), 147.1 (7a-C), 138.8 (3-C), 130.2 (40-C), 128.8 (30-C,
50-C), 126.5 (20-C, 60-C), 125.4 (10-C), 88.1 (7-C), 59.7
(–O–CH2CH3), 46.0 (1-N–CH2CH3), 15.7 (6-C–CH3), 15.5
(–N–CH2CH3), 14.4 (–O–CH2CH3); MS (54 eV) m/z: 298
Alkylation with allyl bromide in the presence of anhydrous
K2CO3 and KI: 0.364 g (2.6 mmol) of finely ground
K2CO3 and 0.5 g (1.85 mmol) of 2 were added to a solution
of 0.24 mL (2.77 mmol) allyl bromide and 0.34 g
(2.0 mmol) of finely ground KI in 15 mL MEK. After heat-
ing the reaction mixture to 70 ꢂC for 4 h, the solid residue
was filtered off and the filtrate was evaporated to dryness
on a rotavapor. The resulting solid mass was dissolved in
20 mL ethyl acetate and the solution was washed twice
with 10 mL distilled water and dried with anhydrous
Na2SO4. After evaporating the ethyl acetate, the product
was obtained as a white powder.
+
+
+
ꢁ
(M , 100%), 283 (M ꢀ CH3, 6%), 270 (M ꢀH2C]CH2,
+
ꢁ
9%), 253 (M ꢀ OC2H5, 25%). Anal. Calcd (%) for
C16H18N4O2: C, 64.41; H, 6.08; N, 18.78. Found (%): C,
64.02; H, 5.94; N, 18.03.
Alkylation with ethyl bromide in NaOH/DMF: 0.1 g
(0.37 mmol) of 2 and 0.058 mL (0.77 mmol) of CH3CH2Br
were added to a solution of 0.1 g (2.5 mmol) of NaOH in
5 mL DMF under continuous stirring. After stirring for
1 h, the product was precipitated in 20 mL distilled water
and filtered. Yield: 0.07 g of white powder, 62%; mp: 112–
116 ꢂC (n-hexane); identical with the product prepared by
the previous method (TLC, IR, NMR and MS).
Yield: 0.5 g, 86.5%; mp: 94–97 ꢂC (n-hexane); IR (KBr)
nmax: 3084, 3061, 2981, 2935, 1678, 1643, 1599, 1490,
763, 685 cmꢀ1; dH (CDCl3, 400 MHz): 8.39–8.36 (m, 2H,
20-H, 60-H), 7.53–7.44 (m, 3H, 30-H, 50-H, 40-H), 6.12–6.02
(qt, 1H, J10-H,
¼5.6 Hz, J10-H,
¼12.2 Hz, 10-H),
9-H
11-H
5.26–5.21 (m, 4H, 2ꢃ9-H, 11-H, 12-H), 4.33 (q, 2H,
J¼7.1 Hz, –O–CH2CH3), 2.61 (s, 3H, 6-C–CH3), 1.39 (t,
3H, J¼7.1 Hz, –O–CH2CH3); dC (CDCl3, 100 MHz):
163.2 (C]O), 160.9 (6-C), 147.5 (7a-C), 139.2 (3-C),
132.6 (10-C), 130.3 (40-C), 128.8 (30-C, 50-C), 126.6
(20-C, 60-C), 125.3 (10-C), 118.2 (11,12-C), 88.3 (7-C),
59.8 (–O–CH2CH3), 52.7 (9-C), 15.7 (6-C–CH3), 14.5
(–O–CH2CH3); MS (54 eV) m/z: 310 (M+, 100%), 283
4.2.2. 1,6-Dimethyl-7-ethoxycarbonyl-3-phenyl-6-pyra-
zolo[5,1-c][1,2,4]triazole (7a). Alkylation with dimethylsul-
fate in NaOH/DMF: 0.675 g (2.5 mmol) of 2 and 0.26 mL
(2.75 mmol) of Me2SO4 were added to a solution of 0.4 g
(10 mmol) of NaOH in 10 mL dimethylformamide (DMF)
under continuous stirring. After stirring for 1 h at room tem-
perature, the product was precipitated in 20–30 mL distilled
water and filtered.
+
+
(M ꢀCH2]CHꢁ, 8%), 281 (M ꢀ C2H5 , 13%), 265
ꢁ
ꢁ
+
ꢁ
ꢁ
(M ꢀ OC2H5 , 23%). Anal. Calcd (%) for C17H18N4O2: C,
65.79; H, 5.85; N, 18.05. Found (%): C, 65.54; H, 5.43; N,
17.53.
Yield: 0.67 g of white powder, 92%; mp: 138–139 ꢂC
(n-hexane); IR (KBr) nmax: 3065, 2980, 2937, 2909, 1677,
1609, 1492, 775, 688 cmꢀ1; dH (CDCl3, 400 MHz): 8.36–
8.34 (m, 2H, 20-H, 60-H), 7.53–7.43 (m, 3H, 30-H, 40-H,
50-H), 4.32 (q, 2H, J¼7.1 Hz, –O–CH2CH3), 4.23 (s, 3H,
1-N–CH3), 2.60 (s, 3H, 6-C–CH3), 1.39 (t, 3H, J¼7.1 Hz,
–O–CH2CH3); dC (CDCl3, 100 MHz): 163.2 (C]O),
160.9 (6-C), 147.8 (7a-C), 138.8 (3-C), 130.2 (40-C), 128.8
(30-C, 50-C), 126.4 (20-C, 60-C), 125.2 (10-C), 88.1 (7-C),
59.7 (–O–CH2CH3), 37.9 (1-N–CH3), 15.6 (6-C–CH3),
14.5 (–O–CH2CH3); MS (54 eV) m/z: 284 (M+, 100%),
4.2.4. 1-Benzyl-7-ethoxycarbonyl-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazole (9a). Alkylation with benzyl
bromide in MEK, in the presence of K2CO3 and KI: 0.27 g
(1.9 mmol) of finely ground K2CO3 and 0.4 g (1.48 mmol)
of 2 were added to a solution of 0.23 mL (1.93 mmol) of
benzyl bromide and 0.27 g (1.63 mmol) of finely ground
KI in 12 mL MEK. After heating the reaction mixture to
70 ꢂC for 4 h, the solid residue was filtered off and the filtrate
was evaporated to dryness on a rotavapor. The resulting solid
mass was dissolved in 20 mL ethyl acetate and the solution
was washed twice with 10 mL distilled water and dried with
anhydrous Na2SO4. After evaporating the solvent, the prod-
uct was obtained as a white powder.
+
+
ꢁ
ꢁ
269 (M ꢀ CH3 , 2%), 256 (M ꢀCH2]CH2, 21%), 239
+
ꢁ
ꢁ
(M ꢀ OC2H5 , 37%). Anal. Calcd (%) for C15H16N4O2: C,
63.37; H, 5.67; N, 19.71. Found (%): C, 63.17; H, 5.34; N,
19.55.
Alkylation with methyl iodide in NaOH/DMF: 0.1 g
(0.37 mmol) of 2 and 0.023 mL (0.37 mmol) of CH3I were
added to a solution of 0.1 g (2.5 mmol) of NaOH in 5 mL
DMF under continuous stirring. After stirring for 1 h at
room temperature, the product was precipitated in 10–
15 mL distilled water and filtered. Yield: 0.08 g of white
powder, 76.5%; mp: 138–139 ꢂC (n-hexane); identical
Yield: 0.53 g, 91%; mp: 145–147 ꢂC (n-hexane); IR (KBr)
nmax: 3064, 2981, 2936, 2910, 1682, 1601, 1489, 1543,
767, 712, 692 cmꢀ1; dH (DMSO-d6, 300 MHz): 8.32–8.29
(m, 2H, 20-H, 60-H), 7.62–7.53 (m, 3H, 30-H, 50-H, 40-H),
7.39–7.28 (m, 5H, 200-H, 600-H, 300-H, 500-H, 400-H), 5.81 (s,
2H, –CH2–Ph), 4.23 (q, 2H, J¼7.1 Hz, –O–CH2CH3), 2.53

V. Badea et al. / Tetrahedron 63 (2007) 1467–1473
1471
(s, 3H, 6-C–CH3), 1.21 (t, 3H, J¼7.1 Hz, –O–CH2CH3); dC
(DMSO-d6, 75 MHz): 162.2 (C]O), 160.1 (6-C), 150.1 (7a-
C), 138.4 (3-C), 136.7 (100-C), 130.8 (40-C), 129.2 (30-C, 50-
C), 128.7 (200-C, 600-C), 127.8 (400-C), 127.2 (300-C, 500-C),
126.1 (20-C, 60-C), 124.5 (10-C), 96.7 (7-C), 59.6 (–O–
CH2CH3), 53.2 (–CH2–Ph), 15.4 (6-C–CH3), 14.2 (–O–
CH2CH3); MS (54 eV) m/z: 360 (M+, 64%), 331
7.2 Hz, 1-N–CHo), 4.19 (q, 2H, J¼7.0 Hz, –O–CH2CH3),
3.66 (s, 3H, –O–CH3), 2.48 (s, 3H, 6-C–CH3), 1.83 (d, 3H,
J¼7.2 Hz, CH3–CHo), 1.25 (t, 3H, J¼7.0 Hz, –O–
CH2CH3); dC (DMSO-d6, 75 MHz): 170.2 (pCH–C]O),
162.1 (7-C–C]O), 159.9 (6-C), 147.2 (7a-C), 138.1 (3-C),
130.8 (40-C), 129.1 (30-C, 50-C), 126.0 (20-C, 60-C), 124.4
(10-C), 88.2 (7-C), 59.6 (–O–CH2CH3), 57.4 (–O–CH3),
52.7 (pCH–CH3), 15.8 (6-C–CH3), 15.2 (pCH–CH3), 14.1
(–O–CH2CH3); MS (54 eV) m/z: 356 (M+, 46%), 311
+
+
ꢁ
ꢁ
ꢁ
ꢁ
(M ꢀ C2H5 , 5%), 315 (M ꢀ OC2H5 , 9%), 269
+
+
ꢁ
(M ꢀC6H5CH2 , 7%), 91 (C7H7 , 100%). Anal. Calcd (%)
for C21H20N4O2: C, 69.98; H, 5.59; N, 15.54. Found (%):
C, 69.71; H, 5.19; N, 15.37.
+
+
ꢁ
ꢁ
(M ꢀ OC2H5, 7%), 297 (M ꢀ COOCH3, 100%). Anal.
Calcd (%) for C18H20N4O4: C, 60.67; H, 5.66; N, 15.72.
Found (%): C, 60.49; H, 5.32; N, 15.35.
4.2.5. 7-Ethoxycarbonyl-1-(ethoxycarbonyl-methyl)-6-
methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole (10a).
Alkylation with ethyl 2-bromoacetate: 0.4 mL (3.525 mmol)
of BrCH2COOC2H5 was added dropwise over 1 min to a sus-
pension of 0.685 g (2.5 mmol) of 2 and 0.38 g (2.75 mmol) of
K2CO3 in 5 mL MEK. The reaction mixture was heated to
40 ꢂC and stirred for 4 h (TLC monitoring). The resulting
solution was poured into 50 mL distilled water and the pre-
cipitate was filtered and dried.
Alkylation with methyl 2-bromopropionate: 0.3 mL
(2.625 mmol) of methyl 2-bromopropionate and 0.38 g
(2.75 mmol) of K2CO3 were added to a mixture of 0.675 g
(2.5 mmol) of 2 in 10 mL MEK. After stirring and refluxing
the reaction mixture for 4 h, the solution was poured into
50 mL distilled water and the solid product was filtered
and dried. Yield: 0.45 g of white powder, 50%; identical
with the product prepared by the previous method (TLC,
IR, MS and NMR).
Yield: 0.28 g of white powder, 31%; mp: 103–105 ꢂC (meth-
anol); IR (KBr) nmax: 3063, 2992, 2972, 2934, 1751, 1701,
4.2.7. 7-Ethoxycarbonyl-1-(1-methoxycarbonyl-propyl)-
6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole (12a).
Alkylation with methyl 2-bromobutyrate: 0.43 g (2.6 mmol)
of KI was added to a solution of 0.3 mL (2.625 mmol) of
methyl 2-bromobutyrate in 10 mL MEK and the resulting
mixture was heated to 50 ꢂC for 10 min. Another 0.675 g
(2.5 mmol) of 2 and 0.38 g (2.75 mmol) of K2CO3 were
then added. After stirring and refluxing for 8 h, the solution
was poured into distilled water and the solid product was fil-
tered and dried.
1605, 1543, 1494, 1453, 1227, 1125, 1094, 768, 690 cmꢀ1
;
dH (CDCl3, 400 MHz): 8.38–8.36 (m, 2H, 20-H, 60-H),
7.53–7.45 (m, 3H, 30-H, 50-H, 40-H), 5.36 (s, 2H, 1-N–
CH2), 4.29 [q, 2H, J¼7.1 Hz, (7-C)–O–CH2CH3], 4.24 [q,
2H, J¼7.1 Hz, (1-N)–O–CH2CH3], 2.61 (s, 3H, 6-C–CH3),
1.36 [t, 3H, J¼7.1 Hz, (7-C)–O–CH2CH3], 1.27 [t, 3H,
J¼7.1 Hz, (1-N)–O–CH2CH3]; dC (CDCl3, 100 MHz):
167.6 (–CH2–C]O), 163.1 (7-C–C]O), 160.9 (6-C),
148.2 (7a-C), 139.7 (3-C), 130.5 (40-C), 128.8 (30-C, 50-C),
126.7 (20-C, 60-C), 124.5 (10-C), 88.8 (7-C), 61.9 [(1-N)–
O–CH2CH3], 59.8 [(6-C)–O–CH2CH3], 51.9 (1-N–CH2–),
15.5 (6-C–CH3), 14.4 [(1-N)–O–CH2CH3], 14.1 [(7-C)–O–
CH2CH3]; MS (54 eV) m/z: 356 (M+, 49%), 328
Yield: 0.3 g, 30%; mp: 95–97 ꢂC; IR (KBr) nmax: 3068,
2970, 2951, 2928, 2870, 1753, 1681, 1602, 1543,
1490, 1215, 1160, 1118, 765, 690 cmꢀ1; dH (DMSO-d6,
200 MHz): 8.42–8.30 (m, 2H, 20-H, 60-H), 7.68–7.55 (m,
3H, 30-H, 50-H, 40-H), 5.97 (t, 1H, J¼6.3 Hz, 1-N–CHo),
4.25 (q, 2H, J¼7.0 Hz, –O–CH2CH3), 3.69 (s, 3H, –O–
CH3), 2.54 (s, 3H, 6-C–CH3), 2.43–2.28 (m, 2H, CH3–
CH2–CHo), 1.32 (t, 3H, J¼7.0 Hz, –O–CH2CH3), 0.98 (t,
3H, J¼7.2 Hz, CH3–CH2–CHo); dC (DMSO-d6, 50 MHz):
169.4 (pCH–C]O), 162.1 (7-C–C]O), 159.9 (6-C),
147.0 (7a-C), 138.6 (3-C), 130.8 (40-C), 129.0 (30-C, 50-C),
126.2 (20-C, 60-C), 124.5 (10-C), 88.1 (7-C), 62.9 (–O–
CH3), 59.6 (–O–CH2CH3), 52.6 (CH3–CH2–CHo), 23.2
(CH3–CH2–CHo), 15.3 (6-C–CH3), 14.2 (–O–CH2CH3),
10.7 (CH3–CH2–CHo); MS (54 eV) m/z: 370 (M+, 45%),
+
+
ꢁ
(M ꢀCH2]CH2, 1%), 311 (M ꢀ OC2H5, 9%), 283
+
ꢁ
ꢁ
(M ꢀ COOC2H5 , 100%). Anal. Calcd (%) for
C18H20N4O4: C, 60.67; H, 5.66; N, 15.72. Found (%): C,
60.39; H, 5.39; N, 15.57.
4.2.6. 7-Ethoxycarbonyl-1-(1-methoxycarbonyl-ethyl)-6-
methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole (11a).
Alkylation with methyl 2-chloropropionate: 0.15 g
(0.88 mmol) of KI was added to a mixture of 0.1 mL
(0.88 mmol) of methyl 2-chloropropionate in 5 mL MEK.
The mixture was heated to 50–60 ꢂC for 10 min and another
0.22 g (0.8 mmol) of 2 and 0.11 g (0.8 mmol) of K2CO3
were added. After 4 h of refluxing the chromatographic
test revealed the presence of unreacted starting materials.
To the reaction mixture an excess of 3 mL butanone,
0.055 g (0.4 mmol) of K2CO3, 0.1 g (0.66 mmol) of NaI
and 0.089 mL (0.78 mmol) of methyl 2-chloropropionate
were added. After stirring and refluxing for another 4 h,
the solution was poured into 50 mL distilled water and the
solid product was filtered and dried.
+
+
ꢁ
ꢁ
325 (M ꢀ OC2H5, 5%), 311 (M ꢀ COOCH3, 100%).
Anal. Calcd (%) for C19H22N4O4: C, 61.61; H, 5.99; N,
15.13. Found (%): C, 61.37; H, 5.58; N, 14.89.
4.3. Alkylation of 1H-6-methyl-3-phenyl-pyrazolo
[5,1-c][1,2,4]triazole (1)
4.3.1. 1,6-Dimethyl-3-phenyl-pyrazolo[5,1-c][1,2,4]tri-
azole (13a). Alkylation with dimethylsulfate in 5% NaOH
solution: 5.8 mL 5% NaOH solution (7.7 mmol NaOH)
was added dropwise to a mixture of 0.1 g (0.5 mmol) of 1
and 0.2 mL (2.15 mmol) of (CH3)2SO4 at room temperature
and under continuous stirring. After refluxing the reaction
Yield: 0.13 g of white powder, 45%; mp: 153–155 ꢂC; IR
(KBr) nmax: 3069, 2978, 2959, 2928, 2872, 1754, 1680,
1605, 1546, 1490, 1214, 1157, 1117, 768, 691 cmꢀ1; dH
(DMSO-d6, 300 MHz): 8.30–8.27 (m, 2H, 20-H, 60-H),
7.61–7.54 (m, 3H, 30-H, 50-H, 40-H), 6.02 (q, 1H, J¼

1472
V. Badea et al. / Tetrahedron 63 (2007) 1467–1473
mixture for 4 h, the product was extracted with ethyl acetate.
The organic layer was washed successively with 10 mL dis-
tilled water, 10 mL 5% NaOH solution and finally with
another 10 mL of water. The resulting organic layer was
dried with anhydrous Na2SO4 and the solvent was removed
using a rotavapor.
4.3.3. 1-(Carboxy-methyl)-6-methyl-3-phenyl-pyr-
azolo[5,1-c][1,2,4]triazole (15a). Alkylation with chloro-
acetic acid: 2 mL 5% NaOH solution was added dropwise
and under continuous stirring to a mixture of 0.24 g
(2.5 mmol) of ClCH2COOH in 1 mL distilled water and
2 g ice. To the previous solution a solution of 0.5 g
(2.5 mmol) of 1 in 1 mL 10% NaOH was added. The result-
ing reaction mixture was heated to 80–90 ꢂC and the pH was
maintained at 8–9 by adding 5% NaOH until the reaction
was completed (TLC monitoring). By the end of the process,
the pH increased slightly and the heating was left on for an-
other 30 min. The reaction mixture was filtered. The filtrate
was acidified with 15% aq HCl until the pH decreased to 2–3
and it was filtered again.
Yield: 0.072 g of white powder, 68%; mp: 62–63 ꢂC; IR
(KBr) nmax: 3127, 3059, 2926, 1606, 1467, 1080, 765,
690 cmꢀ1; dH (DMSO-d6, 300 MHz): 8.35–8.32 (m, 2H,
20-H, 60-H), 7.60–7.47 (m, 3H, 30-H, 40-H, 50-H), 5.72 (7-
C–H), 3.85 (s, 3H, 1-N–CH3), 2.32 (s, 3H, 6-C–CH3); dC
(DMSO-d6, 75 MHz): 157.4 (6-C), 148.6 (7a-C), 136.6 (3-
C), 129.8 (40-C), 128.9 (30-C, 50-C), 125.7 (10-C), 125.4
(20-C, 60-C), 77.2 (7-C), 36.51 (1-N–CH3), 14.8 (6-C–
CH3); MS (54 eV) m/z: 212 (M+, 100%). Anal. Calcd (%)
for C12H12N4: C, 67.91; H, 5.70; N, 26.40. Found (%): C,
67.75; H, 5.57; N, 26.23.
Yield: 0.37 g of white powder, 48%; mp: 190–192 ꢂC; IR
(KBr) nmax: 3065, 2992, 2953, 1712, 1608, 1475, 1214,
1108, 765, 716, 690 cmꢀ1; dH (DMSO-d6, 400 MHz):
13.17 (br s, 1H, –COOH), 8.38–8.35 (m, 2H, 20-H, 60-H),
7.60–7.47 (m, 3H, 30-H, 40-H, 50-H), 5.75 (7-C–H), 5.06 (s,
2H, 1-N–CH2–), 2.35 (s, 3H, 6-C–CH3); dC (DMSO-d6,
100 MHz): 169.0 (C]O), 157.5 (6-C), 148.8 (7a-C),
137.2 (3-C), 129.9 (40-C), 128.9 (30-C, 50-C), 125.6 (20-C,
60-C), 125.4 (10-C), 78.2 (7-C), 50.6 (1-N–CH2–), 14.7 (6-
C–CH3); MS (54 eV) m/z: 256 (M+, 100%), 211 (M+ꢀ45,
69%). Anal. Calcd (%) for C13H12N4O2: C, 60.93; H, 4.72;
N, 21.86. Found (%): C, 60.76; H, 4.49; N, 21.47.
Alkylation with methyl iodide in MEK, in the presence of
K2CO3: 0.125 mL (2.0 mmol) of CH3I was added to a mix-
ture of 0.1 g (0.5 mmol) of 1 and 0.14 g (1.0 mmol) of
K2CO3 in 8 mL butanone, under continuous stirring, at
a maximum temperature of 40 ꢂC. After heating to 40 ꢂC
and stirring for 5 h, the reaction mixture was discharged
into 20 mL distilled water and the product was extracted
with 20 mL ethyl acetate. The organic layer was washed suc-
cessively with 10 mL distilled water, 10 mL 5% NaOH solu-
tion and finally with another 10 mL of water. The resulting
organic layer was dried with anhydrous Na2SO4 and the sol-
vent was removed using a rotavapor. Yield: 0.053 g, 50%;
mp: 62–63 ꢂC; identical with the product prepared by the
previous method (TLC, IR, NMR and MS).
4.4. General procedure for the hydrolysis–decarboxyl-
ation of 1-alkyl-7-ethoxycarbonyl-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazole derivatives
A mixture of 1.54 mmol 1-alkyl-7-ethoxycarbonyl-3-phen-
yl-6-methyl-pyrazolo[5,1-c][1,2,4]triazole in 10 mL 80%
H2SO4/AcOH 2:8 (v/v) mixture was refluxed for 17–20 h
(TLC monitoring). The resulting solution was poured into
100 mL distilled water and the pH was brought to neutral
by adding Na2CO3. The product was extracted with
3ꢃ15 mL ethyl acetate. The organic layer was dried over an-
hydrous Na2SO4 and then the solvent was removed using
a rotavapor.
4.3.2. 1-(Ethoxycarbonyl-methyl)-6-methyl-3-phenyl-
pyrazolo[5,1-c][1,2,4]triazole (14a). Alkylation with ethyl
2-bromoacetate: a solution of 0.3 mL (2.52 mmol) of ethyl
2-bromoacetate in 3 mL absolute ethanol was added drop-
wise to a solution of 0.42 g (2.52 mmol) of 1 in 3 mL
EtONa/EtOH solution (2.52 mmol EtONa), under continu-
ous stirring, at the water bath temperature. After completing
the reaction at room temperature for 2 h, the reaction mix-
ture was diluted with 10 mL distilled water and the product
was extracted with 3ꢃ10 mL ethyl acetate. The ethyl acetate
layer was washed successively with 3ꢃ5 mL 5% NaOH
solution, followed by 2ꢃ5 mL water. The resulting solution
was dried over anhydrous Na2SO4 and the solvent was
removed using a rotavapor.
4.4.1. 1-Ethyl-6-methyl-3-phenyl-pyrazolo[5,1-c]-
[1,2,4]triazole (16a). Yield: 0.26 g of pink powder, 76%;
mp: 63–65 ꢂC; IR (KBr) nmax: 3134, 3058, 2981, 2934,
1598, 1469, 1191, 1081, 765, 692 cmꢀ1; dH (DMSO-d6,
300 MHz): 8.36–8.33 (m, 2H, 20-H, 60-H), 7.59–7.46 (m,
3H, 30-H, 40-H, 50-H), 5.74 (7-C–H), 4.17 (q, 2H,
J¼7.2 Hz, –CH2CH3), 2.32 (s, 3H, 6-C–CH3), 1.40 (t, 3H,
J¼7.2 Hz, –CH2CH3); dC (DMSO-d6, 75 MHz): 157.2 (6-
C), 147.6 (7a-C), 136.6 (3-C), 129.7 (40-C), 128.9 (30-C,
50-C), 125.8 (10-C), 125.5 (20-C, 60-C), 77.5 (7-C), 44.8
(–CH2–CH3), 14.8 (6-C–CH3), 13.6 (–CH2–CH3); MS
Yield: 0.26 g, 40%; mp: 80–82 ꢂC; IR (KBr) nmax: 3059,
2982, 2935, 1739, 1617, 1537, 1472, 1219, 1107, 1024,
765, 692 cmꢀ1; dH (DMSO-d6, 300 MHz): 8.38–8.35 (m,
2H, 20-H, 60-H), 7.61–7.52 (m, 3H, 30-H, 50-H, 40-H), 5.75
(s, 1H, 7-C–H) 5.19 (s, 2H, 1-N–CH2–), 4.17 (q, 2H,
J¼7.1 Hz, –O–CH2CH3), 2.34 (s, 3H, 6-C–CH3), 1.20 (t,
3H, J¼7.1 Hz, –O–CH2CH3); dC (DMSO-d6, 75 MHz):
167.7 (–CH2–C]O), 157.6 (6-C), 148.8 (7a-C), 137.5
(3-C), 130.15 (40-C), 129.0 (30-C, 50-C), 125.7 (20-C, 60-C),
125.4 (10-C), 78.4 (7-C), 61.3 (–O–CH2CH3), 50.6 (1-N–
CH2–), 14.8 (6-C–CH3), 14.0 (–O–CH2CH3); MS (54 eV)
+
+
ꢁ
(54 eV) m/z: 226 (M , 100%), 211 (M ꢀ CH3, 9%), 197
+
ꢁ
(M ꢀ C2H5, 9%). Anal. Calcd (%) for C13H14N4: C,
69.00; H, 6.24; N, 24.76. Found (%): C, 68.83; H, 6.11; N,
24.47.
4.4.2. 1,6-Dimethyl-3-phenyl-pyrazolo[5,1-c][1,2,4]tri-
azole (13a). Yield: 0.21 g of brownish powder, 66%; mp:
61–63 ꢂC. The product is identical with that obtained by
alkylating compound 1 with dimethylsulfate (TLC, IR,
NMR and MS).
+
+
ꢁ
m/z: 284 (M , 100%), 211 (M ꢀ COOC2H5, 93%). Anal.
Calcd (%) for C15H16N4O2: C, 63.37; H, 5.67; N, 19.71.
Found (%): C, 63.12; H, 5.38; N, 19.51.

V. Badea et al. / Tetrahedron 63 (2007) 1467–1473
1473
2001 (Eastman Kodak Co., USA); Mura, A. J., Jr.; Eiff, S. L.;
Russo, G. M. U.S. 6348306, 2002 (Eastman Kodak Co., USA).
4. Arakawa, J. EP 1136530, 2001 (Fuji Photo Film Co.).
5. Katsunori, K.; Takayuki, S.; Hiromi, I., JP 167305, 2002
(Konica Co., Japan).
6. Plos, G.; Lagrange, A. EP 1062937, 2000 (L0Oreal).
7. Andousset, M. EP 1040818, 2000 (L0Oreal).
8. Bercean, V.-N.; Costea, L. V.; Badea, V.; Merz, A. Book of
Abstract MP-22, XXIst European Colloquium on Heterocyclic
Chemistry, Sopron, Hungary, September 12–15, 2004.
9. Csunderlik, C.; Bercean, V.-N.; Peter, F.; Badea, V. ARKIVOC
2002, ii, 133–141, http://www.arkat-usa.
4.4.3. 1-Benzyl-6-methyl-3-phenyl-pyrazolo[5,1-
c][1,2,4]triazole (17a). Yield: 0.39 g of white powder,
90%; mp: 94–96 ꢂC; dH (DMSO-d6, 200 MHz): 8.45–8.29
(m, 2H, 20-H, 60-H), 7.65–7.47 (m, 3H, 30-H, 50-H, 40-H),
7.45–7.30 (m, 5H, 200-H, 600-H, 300-H, 500-H, 400-H), 5.48 (s,
1H, 7-H), 5.35 (s, 2H, –CH2–), 2.31 (s, 3H, 6-C–CH3); dC
(DMSO-d6, 50 MHz): 157.3 (6-C), 147.9 (7a-C), 137.1 (3-
C), 135.5 (100-C), 129.7 (40-C), 128.8 (30-C, 50-C), 128.6
(200-C, 600-C), 128.0 (300-C, 500-C), 127.5 (400-C), 125.7
(20-C, 60-C), 126.5 (10-C), 77.8 (7-C), 53.4 (–CH2–), 14.8
(6-C–CH3); MS (54 eV) m/z: 288 (M+, 55%), 197
+
+
ꢁ
(M ꢀC6H5CH2 , 10%), 91 (C7H7 , 100%). Anal. Calcd
(%) for C18H16N4: C, 74.98; H, 5.59; N, 19.43. Found
(%): C, 74.71; H, 5.33; N, 19.02.
10. Bercean, V.-N.; Badea, V.; Venter, M.; Medeleanu, M.;
Csunderlik, C. ARKIVOC 2005, x, 130–138, http://www.arkat-
usa.
11. Bercean, V.; Badea, V.; Iorga, R.; Csunderlik, C. Revista de
Chimie 2003, 54, 533–534.
References and notes
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2004, 55, 1018–1021.
13. Costea, L. V.; Bercean, V.-N.; Badea, V.; Chiriac, C. Revista de
Chimie 2006, 57, 71–75.
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