Synthesis of fluorine containing N-benzyl-1,2,3-triazoles and N-methyl-pyrazoles from conjugated alkynes

Article abstract of DOI:10.1002/jhet.5570430321

1, 3-Dipolar-cycloaddition reaction of fluoro substituted 3-aryl-propynenitriles 1 with benzyl azide 2 afforded the expected 3-benzyl-5-aryl-3H-[1, 2, 3]triazole-4-carbonitrile 3 and 1-benzyl-5-aryl-1H-[1, 2, 3]-triazole-4-carbonitrile 4 in good yield. Ho

Full text of DOI:10.1002/jhet.5570430321

May-Jun 2006
673
Synthesis of Fluorine Containing N-Benzyl-1,2,3-triazoles and
N-Methyl-pyrazoles from Conjugated Alkynes†
V.V.V.N.S. Rama Rao,a B.P.V.Lingaiah,a R.Yadla,a P.Shanthan Rao,a* K.Ravikumar,b
G.Y.S.K. Swamy,b and K. Narsimuluc
aFluoroorganic Division, bX-ray Crystallography Division,cNMR Division.
Indian Institute of Chemical Technology, Hyderabad-500007. INDIA.
Received August 27, 2005
4
4
R
R
5
3
3
5
R
R
R
R
PhCH2N3
2
R
z
2
z
2
+
R
1
N
N
R
1
N
N
N
R
5
1
N
4
R
R
Ph
Ph
3
4
3
z
R
R4
2
R
R
R4
R5
R3
R5
1
CH2N2
R3
R2
CN
+
5
CN
R2
N
R1
N
CH3
N
R1
N
6
7
CH3
1, 3-Dipolar-cycloaddition reaction of fluoro substituted 3-aryl-propynenitriles 1 with benzyl azide 2
afforded the expected 3-benzyl-5-aryl–3H-[1,2,3]triazole-4-carbonitrile 3 and 1-benzyl-5-aryl-1H-[1,2,3]-
triazole-4-carbonitrile 4 in good yield. However, 1,3-dipolar cycloaddition of diazomethane 5 with 3-aryl-
propynenitriles 1 resulted in the exclusive formation of N-methyl-pyrazole derivatives 6 and 7.
J. Heterocyclic Chem., 43, 673 (2006).
Introduction.
conjugated alkynes and their use in the synthesis of
biologically important class of heterocyclic compounds
[21-23], we wish to report here, the synthesis of fluoro
substituted 1,2,3-triazoles and N-methyl- pyrazoles via
1,3-dipolar-cycloaddition reactions of disubstituted
alkynes with benzyl azide and diazomethane,
respectively.
1,2,3-Triazoles are an important class of potential
organic molecules as agrochemicals, pharmaceuticals,
dyestuffs and fluorescent whiteners [1]. They have been
used as fungicides, herbicides [2], light stabilizers [3],
optical brightening agents and corrosion retardants [4].
Fluoro-triazoles are effective in the treatment of
neuropathic pain and attention disorders [5]. Similarly,
pyrazole ring is the basic moiety in a number of
agrochemicals, dyes, drugs and anesthetics. They are
being used as psycho-pharmacological agents [6-8], pain
relief agent (e.g., Celecoxib) and cholesterol lowering
agent [9]. Amino- and hydroxy-pyrazoles have been used
as choline esterase inhibitors [10]. Fluorine containing
pyrazole derivatives are reported to posses anticancer and
antiviral activity [11].
Results and Discussion.
2.1. 1,3-Dipolar-cycloaddition Reaction of Alkynes and
Benzyl Azide.
3-Aryl-propynenitriles 1(z = CN) and ethyl 3-(4-fluoro-
phenyl)-propiolate 1 (z = COOEt) are synthesized from
their corresponding ꢀ-oxo-alkylidene-triphenylphosphor-
anes 8 [21] in good yield. The conjugated alkynes on
reacting with benzyl azide in refluxing benzene/toluene
furnished a mixture of two products (Scheme 1). They are
separated by column chromatography and identified as
triazole isomers based on their spectral data. A higher
combined yield (76-86%) of the triazoles is obtained in
toluene than in benzene (2-3%). All the products are new
and the isomers are well characterized by IR, 1H NMR, 13C
A number of methods have been reported for the
synthesis of 1,2,3-triazoles and pyrazoles [12,13]. 1,3-
Dipolar-cycloaddition with alkynic dipolarophiles
represent a versatile method for the synthesis of 1,2,3-
triazoles and pyrazoles [14-20]. As part of our ongoing
research on the synthesis of fluorine containing

674
V.V.V.N.S. Rama Rao, B.P.V.Lingaiah, R.Yadla, P.Shanthan Rao, K.Ravikumar
G.Y.S.K. Swamy, and K. Narsimulu
Vol 43
NMR and mass spectroscopy and the structure of one of the
ppm. The downfield shift of methylene protons in 3a-f
Scheme 1
R4
R5
R4
N3
R4
R5
3
R3
R5
R
R3
z
Toluene
+
2
R
z
2
R
z
+
; 18-20 h
reflux
(76-86%)
R 2
R1
R1
N
N
N
N
R1
Ph
N
N
1
2
Ph
3
4
a) R1=R2=R4=R5=H,R3=F,Z=CN;
b) R1=R5=F,R2=R3=R4=H,Z=CN;
c) R1=R3=R4=F,R2=R5=H,Z=CN;
d) R1=R2=R3=R4=R5=F,Z=CN;
e) R1=R2=R3=R4=R5=H,Z=CN;
f) R1=R2=R4=R5=H, R3=F, Z=CO2C2H5.
products 3e is confirmed by single crystal X-ray analysis.
may be explained by the presence of nitrile function at
ortho position. This is also reflected in the CMR spectra
of compounds 3a and 4a. The methylene carbon of the
benzyl group appeared slightly down field at ꢀ 54.3 ppm
for 3a, when compared to its position at ꢀ 52.5 ppm in
the case of 4a. Based on spectral data the compounds
3a-f are characterized as 5-aryl-3-benzyl-3H-[1,2,3]-
triazole-4-carbonitrile/4-carboxylic acid ethyl ester and
4a-f as 5-aryl-1-benzyl-1H-[1,2,3]triazole-4-carbonitrile/
4-carboxylic acid ethyl ester. This structural assignment
is further evidenced by single crystal X-ray analysis
(Diagram-1) of compound 3e.
Table 1
Synthesis of 1,2,3-Triazoles
Alkyne
Time (h)
Yield (%)
1
3
4
1a
1b
1c
1d
1e
1f
18
18
18.5
18.5
18
51
53
55
60
47
52
32
27
25
17
38
23
20
The triazole positional isomers are distinguished by IR
and NMR spectroscopy. The IR spectra of compounds 3a-
e revealed the –CN stretching absorption in the region
2230-2236 cm-1, whereas in compounds 4a-e, it appeared
in the region 2241-2245 cm-1. The proton nmr spectra of
compounds 3a-f and 4a-f showed characteristic difference
in the signal for benzylic protons. The signal for
methylene protons of the benzyl group in compounds 3a-f
appeared in the region ꢀ 5.69-5.75 ppm, whereas, in
compounds 4a-f, it appeared in the region ꢀ 5.52-5.54
2.2 1,3-Dipolar Cycloaddition of Alkynes and
Diazomethane.
The 1,3-dipolar cycloaddition of diazomethane and
acetylenes was first reported by Pechman [24].
Subsequently, many groups have reported this reaction
with symmetrical and unsymmetrical acetylenic
compounds resulting in pyrazole derivatives. However,
the structural assignments of the resultant pyrazoles were
Diagram-1. X-ray crystallography of 3e

May-Jun 2006
Synthesis of Fluorine Containing N-Benzyl-1,2,3-triazoles and N-Methyl-pyrazoles
675
a challenging problem with unsymmetrical acetylenic
compounds [25-27].
Table 2
Synthesis of N-Methyl-pyrazoles
Conjugated acetylenic nitrile 1 and freshly prepared
diazomethane 5 are reacted at –5 °C temperature for 12 h
under constant stirring. The crude reaction mixture is
passed through a silica column to isolate two new
products along with a small quantity of unreacted
acetylenic nitrile 1. The mass spectra of these two
products revealed same molecular ion indicating that they
are positional isomers of pyrazoles. The proton nmr
spectra revealed the presence of methyl protons in the
region ꢀ 3.91-4.16 ppm indicating that they are
N-methylated pyrazoles 6 and 7.
Alkyne
Time (h)
Yield (%)
6
7
1a
1b
1c
1d
8.5
8.5
9
26
52
16
19
13
59
58
60
9
overlapping with aromatic protons. The significant
difference in 1H NMR spectra of 6 and 7 is in the position
of the lone pyrazole ring proton appearing at ꢀ 7.74 ppm
in compound 6 and at ꢀ 7.51 ppm in 7. The downfield
shift in 6 is due to the proton being attached to the C-C=N
It is presumed that the pyrazole ring is formed by the
1,3-dipolar cycloaddition of diazomethane 5 onto the
Scheme 2
R3
R3
R4
R4
R5
R4
R5
R2
R2
R5
CN
CH2N2
R3
CN
CN
[
-
R1
H
R1
5
]
N
+
R2
N
R1
H
H
N
N
H
1
R4
R4
R3
R3
R3
R4
R4
R3
R5
R5
R2
R2
R5
R5
R2
R2
CH2N2
CN
CN
CN
CN
+
R1
5
R1
R1
R1
N
N
N
N
N
N
N
CH3
N
H
CH3
H
6
9
7
a) R1=R2=R4=R5=H, R3=F;
d) R1=R2=R3=R4=R5=F.
b) R1=R5=F, R2=R3=R4=H;
c) R1=R3=R4=F, R2=R5=H;
acetylene 1. The diazomethane 5 present in the reaction
medium acts as a methylating agent [28-30] resulting
exclusively in the N-methyl-pyrazole derivatives 6 and 7
(Scheme 2). The steps involved in the formation of the
isomeric N-methyl-pyrazole derivatives 6 and 7 from the
alkynenitriles 1 and diazomethane 5 are depicted in
Scheme 2.
The IR spectra of the regioisomers of pyrazoles showed
characteristic strong nitrile absorption in the region 2230-
2239 cm-1. The 1H NMR spectra of compound 6 showed a
signal at ꢀ 4.06-4.16 ppm for methyl protons and the
olefenic proton of pyrazole ring appeared as singlet at ꢀ
7.74-7.94 ppm. In the case of compound 7, the N-methyl
protons appeared at ꢀ 3.91-4.08 ppm and the lone proton
present on the pyrazole ring is seen at ꢀ 7.51-7.82 ppm
function, where as in 7, it is attached to C=C-N part of the
ring. The compounds 6a-d and 7a-d are tentatively
characterized as 4-aryl-2-methyl-2H-pyrazole-3-carbo-
nitrile and 4-aryl-1-methyl-1H-pyrazole-3-carbonitrile
respectively. They are further confirmed by NOED
studies.
In the NOED experiments of compound 6a, the
irradiation of signal at ꢀ 7.74 ppm (s, 1H, C5-H on
pyrazole ring) caused enhancement of the signal of phenyl
ring proton at ꢀ 7.60 ppm (ddd, 1H, meta to –F atom),
while the irradiation of signal at ꢀ 4.09 ppm (s, 3H, N-
CH3) caused no enhancement of the peak at ꢀ 7.74 ppm.
The above information indicates that, in compound 6a, N-
methyl group at ꢀ 4.07 ppm was not close enough with
the olefenic proton of pyrazole ring, while the olefenic

676
V.V.V.N.S. Rama Rao, B.P.V.Lingaiah, R.Yadla, P.Shanthan Rao, K.Ravikumar
G.Y.S.K. Swamy, and K. Narsimulu
Vol 43
MHz, CDCl3): ꢀ 54.3 (s, -CH2-Ph), 106.4 (s), 109.7 (s), 116.2 (d,
proton at ꢀ 7.74 ppm is spatially close enough to the aryl
proton appearing at ꢀ 7.60 ppm (Diagram 2).
4
2JC-F=22.0 Hz, ortho to-F), 123.9 (d, JC-F=3.0 Hz, para to –F),
3
128.3 (s), 128.4 (d, JC-F=9.0 Hz, meta to –F), 129.1 (s), 129.3
In the NOED experiments of compound 7a, the
irradiation of signal at ꢀ 3.94 ppm (s, 3H, N-CH3) caused
enhancement of the peak at ꢀ 7.51 ppm. The irradiation of
signal at ꢀ 7.51 ppm (s, 1H, C5-H of pyrazole ring) caused
enhancement of the peaks at ꢀ 7.49 ppm (ddd, 1H, meta to
–F atom) and ꢀ 3.94 ppm (s, 3H, N-CH3). These results
indicate that, in compound 7a, the olefenic proton at ꢀ
7.51 ppm was close enough to cause the enhancement of
N-methyl group signal at ꢀ 3.94 ppm and spatially close
enough to give the enhancement of the aryl proton signal
at ꢀ 7.49 ppm (Diagram 2).
1
(s), 132.8 (s), 151.5 (s) and 163.7 ppm (d, JC-F=251.1 Hz,
directly attached to –F). EIMS: m/z (relative intensity) 278 (M+,
11), 249 (6), 91 (100%).
Anal. Calcd. for C16H11FN4: C, 69.04; H, 3.98; N, 20.14.
Found: C, 69.07; H, 3.97; N, 20.19.
3.2.2. 3-Benzyl-5-(2,4-difluorophenyl)-3H-[1,2,3]triazole-4-
carbonitrile (3b).
Compound 3b (0.16 g, 53.4%) was obtained as white colour
solid, mp 120 °C. IR (KBr): 3057, 2925, 2233, 1494, 1127 cm-I.
1H NMR (200 MHz, CDCl3): ꢀ 5.75 (s, 2H), 7.02-7.01 (m, 2H)
and 7.37-7.50 ppm (m, 5H). EIMS: m/z (relative intensity) 296
(M+, 12), 249 (35), 267 (82), 249 (10), 197 (51) 91 (100%).
Anal. Calcd. for C16H10F2N4 C, 64.85; H, 3.40; N, 18.92.
Found: C, 64.64; H, 3.51; N, 18.55.
F
F
CN
CN
3.2.3. 3-Benzyl-5-(2,4,5-trifluoro-phenyl)-3H-[1,2,3] triazole-
4-carbonitrile (3c).
N
N
CH3
H
N
H
H
N
H
CH3
Compound 3c (0.17 g, 55.1 %) was obtained as white colour
solid, mp 75 °C. IR (KBr): 3059, 2926, 2236, 1491, 1130 cm-I.
1H NMR (200 MHz, CDCl3): ꢀ 5.73 (s, 2H), 7.07 (m, 1H), 7.36-
7.50 (m, 5H) and 7.84 ppm (m, 2H). EIMS: m/z (relative
intensity) 318 (M+, 12), 285 (18), 195 (4), 142 (4), 91 (100), 65
(55), 51 (9%).
6a
7a
Diagram-2. Spacial interactions observed by NOED experiments
Anal. Calcd. for C16H9F3N4 C, 61.13; H, 2.88; N, 17.83.
Found: C, 61.19; H, 2.51; N, 17.45.
EXPERIMENTAL
3.1. General.
3.2.4. 3-Benzyl-5-(2,3,4,5,6-pentafluorophenyl)-3H-[1,2,3]-
triazole-4-carbonitrile(3d).
Melting points were determined in open glass capillaries on a
Fisher Johnes melting point apparatus and are uncorrected. IR
spectra were recorded on FT-IR Schimadzu Perkin-Elmer 1310
infrared spectrophotometer. H NMR (200 MHz) and 13C NMR
(50 MHz) spectra were recorded on Varian Gemini spectrometer
in CDCl3 solvent using TMS as internal standard. Mass spectra
were recorded on a VG-micro mass 7070H instrument at 70eV.
Elemental analyses were carried out on EI Elemental Vario EL
(Germany) apparatus. Single crystal analysis was carried out on
Bruker SMART Apex CCD difractometer.
Compound 3d (0.21 g, 60.8%) was obtained as liquid, IR
(KBr): 3061, 2924, 2233, 1486, 1131 cm-1. 1H NMR (200 MHz,
CDCl3): ꢀ 5.75 (s, 2H) and 7.39-7.48 ppm (m, 5H). EIMS: m/z
(relative intensity) 350 (M+, 49), 322 (35), 304 (22), 91 (100%).
Anal. Calcd. for C16H7F5N4 C, 54.84; H, 2.01; N, 16.00.
Found: C, 54.98; H, 2.03; N, 16.05.
1
3.2.5. 3-Benzyl-5-phenyl-3H-[1,2,3]triazole-4-carbonitrile (3e).
This compound (0.12 g, 47.3%) was obtained as white solid,
mp112 °C. IR (KBr): 3070, 2930, 2331 cm-1. 1H NMR (200
MHz, CDCl3): ꢀ 5.69 (s, 2H), 7.34-7.56 (m, 7H), 7.97-8.08 ppm
(m, 3H). EIMS: m/z (relative intensity) 260 (M+, 9), 231 (20),
149 (10), 141 (14), 105 (92), 91 (100), 83 (85), 77 (45), 51 (8),
43 (50%).
3.2. General procedure for the Preparation of 1,2,3-Triazoles
(3a-f and 4a-f).
Azidomethylbenzene 2 (1 mmol) and alkynenitrile/ ester 1 (1
mmol) were taken in dry toluene (5 mL) and refluxed for 18-20
h under nitrogen atmosphere. The reaction mixture was cooled,
adsorbed on silica gel (100-200 mesh) and passed through a
silica column for purification and isolation of the products. An
initial fraction of hexane contains toluene and unreacted azide.
Later fractions eluted with ethyl acetate and pet ether (1:9)
afforded the isomer 3a-f first followed by the second isomer 4a-f
which was eluted with a 3:7 mixture of ethyl acetate and pet
ether.
Anal. Calcd. for C16H12N4 C, 73.81; H, 4.64; N, 21.53. Found:
C, 73.84; H, 4.63; N, 21.32.
X-ray Data.
A colorless cube crystal of compound 3e was obtained using
ethanol as solvent. The crystal belongs to the monoclinic crystal
system, space group C2/c with a=13.5305 (17), b=11.1770 (14),
c=17.938(2) Å, ꢀ=90.386(2)°, V=2712.7(6) Å3, Z=8,
ꢁ=0.71073Å, ꢀ(MoKꢂ)=0.080 mm-1, F000 = 1088, T=273(2) K.
Data collection yielded 2385 reflections resulting in 1918 unique
(I>2ꢃI), ꢄ range: 0.995 – 25.0°. Full matrix least-squares
refinement led to a final R=0.0397, wR=0.1035 and GOF
=1.055. Intensity data were measured on Bruker Smart Apex
with CCD area-detector. Crystallographic data for the structure
of 3-benzyl-5-phenyl-3H-[1,2,3] triazole-4-carbonitrile 3e has
3.2.1. 3-Benzyl-5-(4-fluorophenyl)-3H-[1,2,3]triazole-4-carbo-
nitrile (3a).
Compound 3 (0.14 g, 51.2%) was obtained as white colour
solid, mp 89 °C. IR (KBr): 3070, 2930, 2234, 1495, 1128 cm-1.
1H NMR (200 MHz, CDCl3): ꢀ 5.69 (s, 2H), 7.15-7.22 (m, 3H),
7.37-7.49 (m, 5H) and 8.00-8.09 ppm (m, 2H). 13C NMR (50

May-Jun 2006
Synthesis of Fluorine Containing N-Benzyl-1,2,3-triazoles and N-Methyl-pyrazoles
677
been deposited with the Cambridge Crystallographic Data
Center as supplementary publication number CCDC261890.
Compound 4e (0.1 g, 38.7%) was obtained as white colour
solid, mp 79 °C. IR (KBr): 3041, 2239, 1128 cm-1. 1H NMR (200
MHz, CDCl3): ꢀ 5.53 (s, 2H), 7.01-7.14 (m, 2H), 7.13-7.39 (m,
5H) and 7.45-7.61 ppm (m, 3H). EIMS: m/z (relative intensity)
260 (M+, 20), 231 (10), 173 (7), 91 (100), 65 (13), 51 (4%).
Anal. Calcd. for C16H12N4 C, 73.81; H, 4.64; N, 21.53. Found:
C, 73.73; H, 4.65; N, 21.51.
3.2.6. 3-Benzyl-5-(4-fluorophenyl)-3H-[1,2,3] triazole-4-carbox-
ylic acid ethyl ester (3f).
Compound 3f (0.17 g, 52.4%) was obtained as white solid,
1
mp104 °C. IR (KBr): 3050, 1715, 1480, 1284 cm-1. H NMR
(200 MHz, CDCl3): ꢀ 1.23 (t, 3H, J=7.0Hz), 4.23 (q, 2H, J=7.0
Hz), 5.88 (s, 2H), 7.01-7.14 (m, 2H), 7.3 (s, 5H) and 7.63-7.76
ppm (m, 2H). EIMS: m/z (relative intensity) 325 (M+, 2), 296
(16), 268 (30), 253 (55), 224 (56), 149 (9), 135 (15), 91 (100%).
Anal. Calcd. for C18H16FN3O2 C, 70.32; H, 5.25; N, 18.23.
Found: C, 70.70; H, 5.75; N, 18.51.
3.2.12. 1-Benzyl-5-(4-fluorophenyl)-1-[1,2,3]triazole-4-carbox-
ylic acid ethyl ester (4f).
Compound 4f (0.07 g, 23.5%) was obtained as white solid,
1
mp 78-79 °C. IR (KBr): 3059, 1726, 1484, 1283 cm-1. H NMR
(200 MHz, CDCl3): ꢀ 1.32 (t, 3H, J=7.0Hz), 4.28 (q, 2H, J=7.0
Hz), 5.42 (s, 2H), 6.97-7.02 (m, 2H), 7.08-7.17 (m, 4H) and
7.23-7.30 ppm (m, 3H). EIMS: m/z (relative intensity) 325 (M+,
2), 296 (12), 268 (27), 253 (45), 224 (46), 91 (100), 65 (30%).
Anal. Calcd. for C18H16FN3O2 C, 70.32; H, 5.25; N, 18.23.
Found: C, 70.73; H, 5.74; N, 18.50.
3.2.7. 1-Benzyl-5-(4-fluorophenyl)-1H-[1,2,3]triazole-4-carbo-
nitrile (4a).
Compound 4a (0.09 g, 32.8%) was obtained as white solid,
mp 68°C. IR (KBr): 3070, 2927, 2243, 1498, 1238 cm-1. 1H
NMR (200 MHz, CDCl3): ꢀ 5.54 (s, 2H), 7.03-7.09 (m, 2H),
7.18-7.23 (m, 2H) and 7.29-7.38 ppm (m, 5H). 13C NMR (50
3.3. General Procedure for the Preparation of Pyrazoles, 6a-d
and 7a-d.
2
MHz, CDCl3): ꢀ 52.5 (s, -CH2-Ph), 111.6 (s), 116.6 (d, JC-
4
F=22.4 Hz, ortho to –F), 119.2 (d, JC-F=3.1 Hz, meta to –F),
Conjugated alkynenitrile 1 (2 mmol) was dissolved in dry
ether (3 mL) and cooled to –5 °C. To this, a cold ethereal
solution (2.7 ml) of diazomethane 5 (0.88 g, 2 mmol) was added
drop wise and stirred for 12 h. The reaction mixture was
adsorbed on silica gel (100-200 mesh) and purified by column
chromatography. The initial hexane fractions gave unreacted
acetylene 1. Elution with hexane and 5% chloroform solvent
mixture gave compound 6. This was followed by elution with
hexane mixed with 10% ethyl acetate to isolate compound 7.
3
120.3 (s), 127.1 (s), 128.5 (s), 131.0 (d, JC-F=8.9 Hz, para to –
1
F), 133.6 (s), 142.7 (s) and 164.0 ppm (d, JC-F=253.3 Hz,
directly attached to –F). EIMS: m/z (relative intensity) 278 (M+,
25), 250 (32), 91 (100%).
Anal. Calcd. for C16H11FN4 C, 69.04; H, 3.98; N, 20.14.
Found: C, 69.16; H, 3.89; N, 20.18.
3.2.8. 1-Benzyl-5-(2,4-difluorophenyl)-1H-[1,2,3]triazole-4-
carbonitrile (4b).
3.3.1. 4-(4-Fluorophenyl)-2-methyl-2H-pyrazole-3-carbonitrile
(6a).
Compound 4b (0.08 g, 27.5%) was obtained as white solid,
mp 84-85 °C. IR (KBr): 3073, 2929, 2245, 1595, 1466, 1260 cm-
1. 1H NMR (200 MHz, CDCl3): ꢀ 5.52 (s, 2H), 6.92-7.0 (m, 2H),
6.98-7.07 (m, 2H), 7.15-7.23 (m, 3H) and 7.52 ppm (m, 1H).
EIMS: m/z (relative intensity) 296 (M+, 5), 267 (7), 91 (100%).
Anal. Calcd. for C16H10F2N4 C, 64.85; H, 3.40; N, 18.92.
Found: C, 64.11; H, 3.53; N, 18.64.
Compound 6a (0.1g, 26%) was obtained as white solid, mp 66
°C. IR (KBr): 2944, 2230, 1611, 1557, 1362, 1162 cm-1. 1H
NMR (200 MHz, CDCl3): ꢀ 4.09 (s, 3H, N-CH3), 7.14 (ddd, 2H,
3
4
3
4
3JH-H=8.8, JH-F=6.4, JH-H=2.2 Hz), 7.6 (ddd, 2H, JH-H=8.8, JH-
F=5.3, JH-H=2.1 Hz) and 7.74 ppm (1H,s). 13C NMR (50 MHz,
4
CDCl3): ꢀ 38.5 (s, CH3), 96.1 (s, C3), 111.6 (s, CN), 116.2 (d,
3.2.9. 1-Benzyl-5-(2,4,5-trifluorophenyl)-1H-[1,2,3] triazole-4-
carbonitrile (4c).
3
2JC-F=21.8 Hz, ortho to-F), 125.5 (s, para to –F), 128.3 (d, JC-
F=8.2 Hz, meta to –F), 129.0 (s, C4), 137.0 (s, C5) and 162.7 ppm
1
Compound 4c (0.08 g, 25.9%) was obtained as white colour
solid, mp 63 °C. IR (KBr): 3055, 2925, 2241, 1490, 1131 cm-I.
1H NMR (200 MHz, CDCl3): ꢀ 5.54 (s, 2H), 6.98 (m, 1H), 7.16
(m, 1H) and 7.23-7.73 ppm (m, 5H). EIMS: m/z (relative
intensity) 314 (M+, 4), 285 (2), 268 (1), 91(100), 65 (7%).
Anal. Calcd. for C16H9F3N4 C, 61.13; H, 2.88; N, 17.83.
Found: C, 61.12; H, 2.79; N, 17.92.
(d, JC-F=248.7 Hz, directly attached to –F). EIMS: m/z (relative
intensity) 201 (M+, 100), 200 (3), 187 (97), 158 (3), 149 (1%).
Anal. Calcd. for C11H8FN3 C, 65.64, H, 4.00, N, 20.89. Found:
C, 65.68, H, 4.03, N, 20.88.
3.3.2. 4-(2,6-Difluorophenyl)-2-methyl-2H-pyrazole-3-carbo-
nitrile (6b).
Compound 6b (0.07 g, 16%) was obtained as white solid, mp
1
3.2.10. 1-Benzyl-5-(2,3,4,5,6-pentafluorophenyl)-1H-[1,2,3]tria-
zole-4-carbonitrile (4d).
74 °C. IR (KBr): 2944, 2235, 1585 cm-1. H NMR (200 MHz,
CDCl3): ꢀ 4.16 (s, 3H, N-CH3), 7.02 (m, 2H), 7.33 (m, 1H) and
7.74 ppm (s, 1H). EIMS: m/z (relative intensity) 219 (M+, 29),
217 (68), 176 (100), 162 (41), 140 (80%).
Anal. Calcd. for C11H7F2N3 C, 60.26; H, 3.22; N, 19.17.
Found: C, 60.29; H, 3.24; N, 19.19.
Compound 4d (0.06 g, 17.16%) was obtained as white colour
solid, mp.72°C. IR (KBr): 3065, 2925, 2243, 1490, 1128 cm-I. 1H
NMR (200 MHz, CDCl3): ꢀ 5.53 (s, 2H), 6.85-6.92 (m, 2H) and
7.15-7.26 ppm (m, 3H). EIMS: m/z (relative intensity) 350 (M+,
30), 322 (26), 91 (100%).
3.3.3 4-(2,4,5-Trifluorophenyl)-2-methyl-2H-pyrazole-3-carbo-
nitrile (6c).
Anal. Calcd. for C16H7F5N4 C, 54.84; H, 2.01; N, 16.00.
Found: C, 54.74; H, 2.09; N, 16.09.
Compound 6c (0.09 g, 19%) was obtained as white solid,
mp.74°C. IR (KBr): 2930, 2234, 1610, 1385 cm-1. 1H NMR (200
MHz, CDCl3): ꢀ 4.12 (s, 3H), 7.09 (m, 1H), 7.47 (m, 1H) and
3.2.11. 1-Benzyl-5-phenyl-1H- [1,2,3] triazole-4-carbonitrile
(4e).

678
V.V.V.N.S. Rama Rao, B.P.V.Lingaiah, R.Yadla, P.Shanthan Rao, K.Ravikumar
G.Y.S.K. Swamy, and K. Narsimulu
Vol 43
7.78 ppm (s, 1H). EIMS: m/z (relative intensity) 237 (M+, 87),
209(56), 181(45%).
Anal. Calcd. for C11H6F3N3 C, 55.68; H, 2.55; N, 17.72.
Found: C, 55.72; H, 2.58; N, 17.81.
The authors are thankful to Dr. J. S. Yadav, Director, IICT,
Hyderabad and to Mr. S.Narayan Reddy, HOD, Fluoroorganic
division for their constant encouragement. VVVNSRR is
thankful to CSIR, New Delhi for the award of senior research
fellowship.
3.3.4. 4-(2,3,4,5,6-Pentafluorophenyl)-2-methyl-2H-pyrazole-3-
carbonitrile (6d).
REFERENCES
Compound 6d (0.07 g, 13%) was obtained as white solid,
mp.129°C. IR (KBr): 2941, 2239, 1375cm-1; 1H NMR (200
MHz, CDCl3): ꢀ 4.06 (s, 3H, -NCH3) and 7.94 ppm (s, 1H).
EIMS: m/z (relative intensity) 273 (M+, 98), 155(78), 141
(100%).
*
Corresponding Author: E-mail: shanthanpp@yahoo.co.in;
Tel.: +91-040-27193185; Fax: +91-040-27160757.
[1] W.-Q. Fan and A.R. Katritzky, in Comprehensive
Heterocyclic Chemistry II– A Review of Literature from 1982-1996;
pergamon: New York, (1996), Vol 4, pp101-104.
[2] F. Reisser, Braz. Pedido PI BR 8101239, (1981); Chem.
Abstr., 96, 69006 (1982).
[3]D. Guenther, H.J. Nestler, G. Roesch and E. Schinzel, Swiss
615164, (1980); Chem. Abstr., 93, 73786 (1980).
[4] A. M. S. Abdennabi, A. I. Abdulhadi, S. T. Abu-Orabi and H.
Saricimen, Corrosion Sci., 38, 1791-1800 (1996).
[5] S. Marcus, WO0051577, (2001); Chem. Abstr., Vol 135, 377328g
(2001).
[6] Y. I. Vikhlyaev, B. I. Jl’inskii, K. S. Raevskii, Y. M. Batulin,
I.I. Grandberg and A.N. Kost, Farmakol. i Toksikol. 1962, 25, 27-32;
Chem. Abstr., 57, 14388d (1962).
[7] R.G. Jones, M. J. Mann, and K. C. McZanghlin, J. Org.
Chem., 19, 428-433 (1954).
Anal. Calcd. for C11H4F5N3 C, 48.34, H, 1.51, N, 15.38.
Found: C, 48.28, H, 1.50, N, 15.29.
3.3.5. 4-(4-Fluorophenyl)-1-methyl-1H-pyrazole-3-carbonitrile
(7a).
Compound 7a (0.2 g, 52%) was obtained as white solid, mp
1
135 °C. IR (KBr): 2925, 2234, 1609,1160 cm-1. H NMR (200
3
MHz, CDCl3): ꢀ 3.94 (s, 3H, N-CH3), 7.06 (ddd, 2H, JH-H=8.8,
4
3
4
4
3JH-F=6.4, JH-F=2.1 Hz), 7.49 (ddd, 1H, JH-H=8.8, JH-H=5.3, JH-
H=2.1 Hz) and 7.51 ppm (s, 1H). 13C NMR (50 MHz, CDCl3): ꢀ
38.7 (s, CH3), 95.1 (s, C3), 113.5 (s, CN), 115.0 (d, JC-F= 21.9
Hz, ortho to-F), 125.5 (s, para to –F), 127.4 (d, JC-F=8.1Hz,
meta to –F), 128.0 (s, C4), 136.7 (s, C5) and 161.3 ppm (d, JC-
2
3
1
F=247.7 Hz, directly attached to –F). EIMS: m/z (relative
intensity) 201 (M+, 100), 200 (3), 187 (97), 158 (3%).
Anal. Calcd. for C11H8FN3: C, 65.64, H, 4.00, N, 20.89.
Found: C, 65.57, H, 4.02, N, 20.77.
[8] M. J. S. Dewar, J. Chem. Soc., 615-619 (1944).
[9] D. R. Sliskovic, C. J. Blankley, B. R. Krause, R. S. Newton,
J. A. Picard, W. H. Roark, B. D. Roth, C. Sekerke, M. K. Shaw and R.
L. Stanfield, J. Med. Chem., 35, 2095-2103 (1992).
[10] G. A. Olah, P. S. Iyer and G. K. S. Prakash, Synthesis, 513-
531 (1986).
3.3.6. 4-(2,6-Difluorophenyl)-1-methyl-1H-pyrazole-3-carbo-
nitrile (7b).
[11] I. M. Abdou, A. M. Saleh and H. F. Zohdi, Molecules, 9, 109-116
(2004), and the references cited therein.
Compound 7b (0.25 g, 59%) was obtained as white solid, mp
153 °C. IR (KBr): 2236, 1378 cm-1. 1H NMR (200 MHz,
CDCl3): ꢀ 3.91 (s, 3H, –NCH3), 6.96 (m, 1H), 7.52 (m, 1H) and
7.82 ppm (s, 1H). EIMS: m/z (relative intensity) 219 (M+, 32),
204 (20), 203 (100%).
[12] T. L Gilchrist and G. E. Gymer, in Advances in Heterocyclic
Chemistry; A.R. Katritzky and A.J. Boulton, eds, Academic: New
York, (1974), Vol 16, pp 33-58.
[13] K. T. Finley, in Triazoles: 1,2,3; J. A. Montgomery. Ed, John
Wiley & Sons: New York, (1980), pp 63-87.
[14] H.G. Viehe, in Chemistry of Acetylenes; Marcel Dekker:
New York, (1969), pp 462-478.
[15] R. Sreedhar and P.T. Perumal, Syn. Commun., 33, 1483-
1488 (2003).
[16] F.Farina, P. Fernandez, M. T. Fraile and M.V. Martin,
Heterocycles, 29, 967-974 (1989).
[17] T. Sasaki and K. Kanematsu, J.Chem.Soc. (C), 1971, 2147-
2150.
Anal. Calcd. for C11H7F2N3 C, 60.26; H, 3.22; N, 19.17.
Found: C, 60.30; H, 3.24; N, 19.06.
3.3.7. 4-(2,4,5-Trifluorophenyl)-1-methyl-1H-pyrazole-3-carbo-
nitrile (7c).
Compound 7c (0.27g, 58%) was obtained as white solid, mp
1
144-145 °C. IR (KBr): 2925, 2235, 1610, 1385 cm-1. H NMR
(200 MHz, CDCl3): ꢀ 3.94 (s, 3H, N-CH3), 6.96 (m, 1H), 7.67
(m, 1H) and 7.67 ppm (s, 1H). EIMS: m/z (relative intensity)
237 (M+, 87), 209(58%).
Anal. Calcd. for C11H6F3N3 C, 55.68; H, 2.55; N, 17.72.
Found: C, 55.71; H, 2.58; N, 17.79.
[18] K. V. Auwers and O. Ungemach, Ber. 66B, 1933, 1205-1210.
[19] S. T. Abu-Orabi, M. A. Atfah and I. Jibril, J. Heterocyclic
Chem., 1989, 26, 1461-1468.
[20] I. Lalezari, L. A. Gomez and M. Khorshidi, J. Heterocyclic
Chem., 1990, 27, 687-689.
[21] V. V. V. N. S. Rama Rao, S. Ravi Kanth, G. Venkat Reddy,
D. Maitraie, R. Yadla and P. Shanthan Rao, Synth. Commun., 2003, 33,
1523-1529.
3.3.8. 4-(2,3,4,5,6-Pentafluorophenyl)-1-methyl-1H-pyrazole-3-
carbonitrile (7d).
[22] V. V. V. N. S. Rama Rao, G. Venkat Reddy, D. Maitraie, S.
Ravikanth, R. Yadla, B. Narsaiah and P. Shanthan Rao, Tetrahedron,
2004, 60, 12331-37.
Compound 7d (0.32 g, 60%) was obtained as white solid, mp
1
129-130 °C. IR (KBr): 2936, 2239, 1569 cm-1. H NMR (200
MHz, CDCl3): ꢀ 4.08 (s, 3H, N-CH3), 7.66 ppm (s, 1H). EIMS:
m/z (relative intensity) 273 (M+, 85), 155(28), 141 (100).
Anal. Calcd. for C11H4F5N3 C, 48.37; H, 1.48; N, 15.38.
Found: C, 48.39; H, 1.51; N, 15.37.
[23] V. V. N. N. S. Rama Rao, G. Venkat Reddy, R. Yadla, B.
Narsaiah and P. Shanthan Rao, Arkivoc, 2005, iii, 211-220.
[24] H. V. Pechmann, Ber., 1898, 31, 2950-2956.
[25] G. Heinisch and W. Holzer, Heterocycles, 1988, 27, 2443-2447.
[26] W. Holzer and G. Seiringer, J. Heterocyclic Chem., 1993, 30,
865-872.
Acknowledgements.

May-Jun 2006
Synthesis of Fluorine Containing N-Benzyl-1,2,3-triazoles and N-Methyl-pyrazoles
679
[27] M. Bruix, J. De Mendoza and J. Elguero, Tetrahedron, 1987,
43, 4663-4668.
[28] J. Bastide and J. Lematre, Bull.Soc.Chim.Fr., 1970, 10, 3543-
3549.
[29] J. Bastide and J. Lematre, C. R. Acad. Sci., Paris, Ser. C,
268(6), 532-535 (1969). Chem. Abstr., 70, 87658 (1969).
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