New generation of functionalized bipyrazolic tripods: Synthesis and study of their coordination properties towards metal cations

Article abstract of DOI:10.1016/j.tet.2012.03.052

A simple and easily synthesis of new generation of N-donor bipyrazolic tripods by coupling of functionalized pyrazole derivatives and an appropriate primary amine derivative via condensation or nucleophilic substitution reaction is presented. The complexation capacity of these compounds towards bivalent metal ions (Hg²⁺, Cu²⁺, Pb²⁺, Cd²⁺) and alkaline metal ions (Li⁺, Na⁺, K⁺) were investigated using the liquid-liquid extraction process. The percentage limits of extraction were determined by atomic absorption measurements.

Full text of DOI:10.1016/j.tet.2012.03.052

Tetrahedron 68 (2012) 4037e4041
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New generation of functionalized bipyrazolic tripods: synthesis and study of their
coordination properties towards metal cations
,
c
a,
Tarik Harit a, Mounir Cherfi a, Jalal Isaad b , Abdelkhalek Riahi , Fouad Malek
*
*
a
ꢀ
ꢀ
ꢀ
Faculte des Sciences-Universite Mohamed Premier, Laboratoire de Chimie Organique, Macromoleculaire et Produits Naturels-URAC 25, Bd Mohamed VI, BP: 717,
60 000 Oujda, Morocco
b University Lille Nord de France, Engineering and Textile Materials Laboratory, F-5900 Lille, France
c
ꢀ
ꢀ
ꢀ
ꢁ
Universite de Reims Champagne-Ardenne, Institut de Chimie Moleculaire de Reims (ICMR)-Groupe Methodologie en Synthese Organique, CNRS UMR 6229,
ˇ
Bat. Europol’Agro-Moulin de la Housse, BP 1039, 51687 Reims Cedex 2, France
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and easily synthesis of new generation of N-donor bipyrazolic tripods by coupling of func-
tionalized pyrazole derivatives and an appropriate primary amine derivative via condensation or nu-
cleophilic substitution reaction is presented. The complexation capacity of these compounds towards
bivalent metal ions (Hg2þ, Cu2þ, Pb2þ, Cd2þ) and alkaline metal ions (Liþ, Naþ, Kþ) were investigated
using the liquideliquid extraction process. The percentage limits of extraction were determined by
atomic absorption measurements.
Received 7 February 2012
Received in revised form 12 March 2012
Accepted 15 March 2012
Available online 21 March 2012
Keywords:
Bipyrazolic tripods
N-Donor
Ó 2012 Elsevier Ltd. All rights reserved.
Complexing properties
Coordination
Liquideliquid extraction
1. Introduction
considered as a potential electron donating because of their two sp2
and sp3 hybridized amine nitrogen atoms where the electronic
Metal ions play an essential role in many biological processes,
and deficiency, unusual accumulation or imbalance of metal ions
may lead to biological dysfunctions.1e5 Some metals, especially
heavy metals, do not seem to be essential for the functioning of
mammals. Nevertheless, because of their competition with essen-
tial metals for binding with proteins, heavy metal ions are potent
enzyme inhibitors exerting toxic effects on living systems.6e9 Re-
distribution of these metals by man through his industrial society
constitutes a major health hazard.10 In this sense, lead, mercury and
cadmium are considered to be major pollutants. Therefore, the
design of selective extractants for the separation of bivalent metal
cation is one of the key problems in wastewater reprocessing.
Pyrazole derivatives are the subject of several studies. They are
used in different fields, such as pharmacology,11e14 biology,15e19
catalysis,20,21 electronics22,23 and particularly, they are used to
remove the divalent metal ions, Hg2þ, Cu2þ, Pb2þ and Cd2þ ions
from aqueous solution containing either a single metal species or
a mixtures of metal ions.24e30 Recently, we have developed and
studied several pyrazolic tripods derivatives.31e40 These ligands are
doublets of these three donor sites are organized according to
a pyramidal form for complexing metal. Regarding the chemical
application of these prepared ligands,31e40 they are characterized
by a good and selective affinity towards the transition metals,31e35
and have an important catalytic26e29 and pharmacological prop-
erties.40,41 These chemical applications depend on the lateral chain
nature of the ligands. In fact, it is reported in the literature that the
presence of a donor atom in a side chain of lariat ethers increases
the binding ability of the macrocycle towards the cations.42e44
Furthermore, ligands with side arms attached to nitrogen (N-
pivot lariat ethers) instead of a carbon (C-pivot lariat ethers)
present best binding properties. This bonding improvement could
be attributed to the high flexibility of the side chain with nitrogen,
which gives to the donor site a best binding capacity.45 Therefore, it
is very interesting to increase the electron density on the lateral
chain of the tridentate ligands to study their extraction ability to-
wards the metal ions. On the other hand, the presence of a func-
tional chain also provides to these ligands the possibility of being
immobilized on the surface of a solid material by covalent bond or
to elaborate some membranes including these tripods in their
structures by polymerization.
* Corresponding authors. Fax: þ33 (0) 3 20 27 25 97 (J.I.); fax: þ212 (0) 5 36 50
06 03 (F.M.); e-mail addresses: jalal.isaad@ensait.fr (J. Isaad), malek_fso@yahoo.fr
(F. Malek).
For these reasons, we report in this paper the synthesis of new
functionalized pyrazolic tripods, starting from the pyrazolic
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.052

4038
T. Harit et al. / Tetrahedron 68 (2012) 4037e4041
derivatives 2 and 4, with different side chains: primary alcohol (6a,
6c), secondary alcohol (3a, 6b), alkyl chain (6e) vinyl benzene group
(6d) and alkenyl group (3b) as reported in Fig. 1, to study the
influence of the side chain nature of these new tripods on their
Ligands 3a,b were prepared by nucleophilic substitution reaction
of compound 2 and the different amines. First, the precursor 3-
chloromethyl-1,5-dimethylpyrazole 2 was prepared from 1 in three
steps following the procedure reported in the literature.46,47 Com-
pound 3a was obtained in good yield (85%) by treating the chloro
derivative with the commercially available 1-aminopropan-2-ol in
aratioof2/1underrefluxusingsodium carbonateasbase. Compound
3b was prepared in 75% yield according to the procedure described
above by reacting allylamine with the synthon chloride (Scheme 1).
complexing properties towards bivalent metal ions (Hg2þ, Cu2þ
,
Pb2þ, Cd2þ) and alkaline metal ions (Liþ, Naþ, Kþ) using a -
liquideliquid extraction process. The relative capacities of these
receptors in extracting these cations were determined by the
measurement of extracted cation percentage by atomic absorption.
Fig. 1. General structures of functionalized bipyrazolic tripods.
2. Results and discussion
2.1. Synthesis
The synthesis of 3a,b and 6aee ligands was obtained following
the procedure reported in Schemes 1 and 2. The synthetic path
depends on the nature and the position of the functional group in
the starting pyrazolic derivatives.
Scheme 2. Synthesis of ligands 1e5. Reagents and conditions (c) CH3CN, reflux, 6 h.
On the other side, the tripods 6aee were prepared by conden-
sation of 4 with different amines 5aee (Scheme 2).
N-Donor tripodal ligands 6a, 6b and 6d were prepared via the
condensation reaction of di-substituted 1-(hydroxylmethyl)-3,5-
dimethyl pyrazole 448 with a series of primary amines as 3-
Scheme 1. Synthesis of ligands 1 and 2. Reagents and conditions: (a) 1dtBuOꢀ Kþ
MeI, 2dLiAlH4, 3dSOCl2; (b) H2NeR.
,

T. Harit et al. / Tetrahedron 68 (2012) 4037e4041
4039
aminopropanol, 1-aminopropan-2-ol and para-aminophenyl etha-
nol in acetonitrile as solvent for 6 h under reflux to afford the
expected tripods in high yield (about 75e85%). Tripods 6a and 6b
display an alkyl chain functionalized, respectively, by primary and
secondary hydroxyl groups. However, tripod 6c presents phenyl
ethoxy group. Tripod 6d, which exhibits a polymerisable styrenic
double bond, was prepared in 70% yield by coupling vinyl aniline
with pyrazolic precursor 4 in acetonitrile but at room temperature
for 2 days because of the low reactivity of the styrenic group. To
evaluate the possible effect of a donor heteroatom in the side chain
on the cations binding, another tripodal compound 6e was pre-
pared without any donor atom in a side chain by condensation of
precursor 4 with the propylamine, according to the same procedure
reported above. All compounds 3a,b and 6aee were characterized
by 1H NMR, 13C NMR, mass spectroscopy and elemental analyses.
already reported in the litterature.31,32 Tripod 7 has a primary al-
cohol function on the lateral arm while the tripod 8 has an alkyl
saturated chain, without any donor atom.
Tripods 3a,b display a good complexation affinity towards Hg2þ
cations. This is probably due to the great donor effect of the sp2
hybridized pyrazolic nitrogen, and also to the disposition of the
three nitrogen atoms allowing the complexation of the metal. In-
deed, the limit values of the Hg2þ extraction are independent to the
nature of the lateral arm on the pyrazoles. As reported in Table 1,
tripod 7 introduces high affinity to complex Cu2þ and the limit
value of Cu2þ extraction is high (z95%). This result can be
explained by the participation of hydroxyl oxygen of the lateral arm
in complexation’s phenomenon. The less important extraction
value of ligand 3a (Ez36%) is probably due to the non flexible
character of the secondary hydroxyl group in this structure. This
result is confirmed in the case of the extraction of Pb2þ it is noted an
important affinity complexation of ligand 7 compared to ligand 3a.
Tripod 3b, which contains an allylic double bond on the lateral arm,
was observed to complex better Cu2þ (Ez75%) and lead (Ez32%)
than the tripod 8. On the other hand, the Cd2þ cation is not well
extracted by the four ligands 3a,b, 7 and 8. In fact, the weakness of
cohesion’s force between the Cd2þ cation and coordination’s sites
of the studied tripods, does not allow the extraction of this cation
from the aqueous solution. This result confirms our reported
results.29,32
2.2. Liquideliquid extraction of individual cations
In order to study the capacity of the prepared pyrazolic tripods
3a,b and 6aee to extract Hg2þ, Cu2þ, Pb2þ, Cd2þ, Liþ, Naþ and Kþ
cations, aqueous solutions (7.10ꢀ5 M in each) containing bivalent
metal ions Hg2þ, Cu2þ, Pb2þ, Cd2þ and alkaline metal ions (Liþ, Naþ,
Kþ) as nitrate metals were extracted with 7.10ꢀ5 M solutions of li-
gands 3a,b and 6aee in chloroform. The percentage limit of ex-
traction was assessed by measuring the concentration of cations in
the aqueous solution by atomic absorption. The temperature and
pH remained constant during all the experiments (25 ꢁC; pH¼7).
The extraction results are reported in Table 1.
In the case of tripods 6aee, as obtained with 3a,b, all prepared
tripods present a good complexing capacity towards Hg2þ cations.
The limit extraction values are high (E >50%) and does not depend
on the nature of the tripods side chain. As reported in the literature,
a donor atom in a side chain of lariat ethers increases the binding
ability of the macrocycle.42e44 In this sense, the comparison be-
tween 6a, 6b and 6c with a donor atom in a side chain and 6e
without a donor atom showed that there is no change in the com-
plexation percentage of Hg2þ. It can be concluded that the com-
plexation of Hg2þ cations arises from the tripod nitrogens without
any effect of the side chain, which confirms the results obtained
with 3a,b in the case of Hg2þ extraction supported by our previous
studies about the strong ability of nitrogen to complex mercury.29,32
On the other hand, the extraction of the Cu2þ is affected by the
nature of the substituents on the lateral chain. As reported in our
previous studies,29,32 compounds 6a and 6c show good affinity
towards Cu2þ (>52%) compared to ligands 6d and 6e. This result
may be explained by the presence of the oxygen atom on the side
chain, which can participate, beside the two pyrazole nitrogens in
the complexation of Cu2þ cations. Also, the contribution of the
oxygen of the hydroxyl group of the tripod 6a in the complexation
of this metal is well promoted, due to the formation of the very
stable five-membered chelating ring.49 The less important value of
extraction for the ligand 6b, (Ez35%), is probably due to the
non flexible character of the secondary hydroxyl group in this
structure. Tripodal ligand 6c presents the best Cu2þ extraction
efficiency (Ez60%), slightly higher than the value observed for
tripod 6a, this is probably due to the hydrophobic nature of the
molecule 6c, which presents a phenyl group on the side chain,
consequently prevents its solubility in the aqueous phase during
the liquideliquid extraction. This is also confirmed by the com-
parison of the Pb2þ extraction results obtained with 6d and 6e. In
fact, Pb2þ cations are better complexated than copper by these
tripods. This is due to great donor effect of the sp2 hybridized
pyrazolic nitrogen, and also to the accurate disposition of the three
nitrogen atoms allowing the complexation of the metal. Compound
6a showed a good affinity towards Pb2þ (z60%) compared to li-
gands 6b and 6e. This result may be explained by the participation
of the hydroxyl lateral chain, beside the two pyrazole nitrogens and
aminic nitrogens in the complexation of this cation. A small
increase of the lead complexation value is also noted with
Table 1
Yields of extraction of various alkali and bivalent metal ions
Mercury Copper Lead
(1.10 A) (1.20 A) (1.20 A) (0.92 A)
Cadmium Lithium Sodium Potassium
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
(0.80 A) (0.98 A) (1.33 A)
3a 48
3b 40
6a 50
6b 56
6c 54
6d 52
6e 55
36
75
52
35
60
40
30
95
33
16
32
60
45
72
65
48
40
20
25
16
15
13
22
20
17
21
20
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
7
8
42
45
Previous studies29,32 have demonstrated that the acyclic pyr-
azoles extract only the transition metal cations. However, the
macrocyclic pyrazolic compounds are expected to form stable
complexes with transition and alkali metals. Herein, the results
reported in Table 1 show that the synthetized acyclic tripods 3a,b
and 6aee present a selective affinity for only the transition metal
cations and no complexation was observed towards the alkali
cations.
To elucidate the effect of the donor oxygen atom and the allylic
double bond of the lateral chain on the complexation of these
metals, we compared the extraction yields of ligands 3a and 3b
with the extraction results obtained from tripods 7 and 8 (Fig. 2)
Fig. 2. Structures of tripods 7 and 8.

4040
T. Harit et al. / Tetrahedron 68 (2012) 4037e4041
compounds 6c and 6d, probably due to their lipophilic character
(phenyl). This confirms the all above-mentioned result. Finally, for
the Cd2þ extraction, all compounds present a low extraction per-
centage, about 22%. Consequently, these structures do not present
a high affinity towards Cd2þ. In fact, the weakness of cohesion’s
force between the Cd2þ cation and the coordination sites of the
studied tripods, does not allow the extraction of this cation from
the aqueous solution.29,32
4.2. Synthesis procedure
4.2.1. Synthesis of 1-[bis(1,5-dimethyl-1H-pyrazol-3-ylmethyl)
amino]propan-2-ol (3a). To a solution of acetonitrile (100 ml)
containing 1-aminopropan-2-ol (3.0ꢂ10ꢀ2 mol) and sodium car-
bonate (18ꢂ10ꢀ2 mol), 3-chloromethyl-1,5-dimethylpyrazole 2
(6ꢂ10ꢀ2 mol) in 50 ml of acetonitrile was added slowly and the
resulting mixture was stirred under reflux for 6 h. The solid crude
was filtered off and the filtrate was concentrated under reduced
pressure. The product was purified by flash chromatography (alu-
mina, CH2Cl2/MeOH: 96/4) to afford 3a in 85% yield. 1H NMR (CDCl3,
3. Conclusion
200 MHz):
d
¼1.05 (d, 3H, eCHOHeCH3, J¼6 Hz); 2.20 (s, 6H,
New bipyrazolic tripods were prepared with different func-
tionalized side chain by coupling of the functionalized pyrazole
derivatives 2, 4 and an appropriate primary amine derivatives via
condensation or nucleophilic substitution reaction. The complexing
properties of these compounds towards bivalent metal cations
(Hg2þ, Cu2þ, Pb2þ, Cd2þ) and alkaline metal ions (Liþ, Naþ, Kþ) were
investigated using the liquideliquid extraction process. These new
acyclic tripod ligands present a high complexation capacity only
with transition metal cations. This is schematically represented in
Fig. 3.
pzCH3); 2.38 (m, 2H, NeCH2eCHOHe); 3.50 (s, 6H, CH3eNpz); 3.65
(s, 4H, pzeCH2eN); 3.75 (m, 1H, eCHOH); 5.95 (s, 2H, Hpz); 13C
NMR (CDCl3, 50 MHz):
d
¼11.5 (CH3epz); 20.50 (eCHOHeCH3); 36.5
(CH3eNpz); 51.30 (NeCH2epz); 61.00 (NeCH2eCHOH); 64.20
(eCHOH); 106.20 (CpzH); 139.80 (CpzCH3); 148.80 (CpzeCH2N); m/
z¼292 [Mþ1]þ (FAB>0); Anal. Calcd for C15H25N5O: C, 61.85; H,
8.59; N, 24.05. Found: C, 62.16; H, 8.06; N, 24.67.
4.2.2. Synthesis
amino]prop-1-ene (3b). In similar procedure, the compounds 3b
was obtained in a 75% as yield. 1H NMR (CDCl3, 200 MHz):
of
3-[bis(1,5-dimethyl-1H-pyrazol-3-ylmethyl)
d¼1.95
(s, 6H, pzCH3); 3.35 (s, 6H, CH3eNpz); 3.45 (s, 4H, pzeCH2eN); 3.68
(d, 2H, NeCH2eCH]; J¼3.3 Hz); 4.85 (m, 2H, eCH]CH2); 5.55 (m,
H, eCH]CH2); 5.75 (s, 2H, pzH); 13C NMR (CDCl3, 50 MHz):
d
¼11.25
(CH3epz); 36.5 (CH3eNpz); 48.50 (NeCH2epze); 53.60
(NeCH2eCH]); 104.20 (CpzH); 113.50 (eCH]CH2); 134.20
(eCH]CH2); 139.50 (CpzCH3); 149.20 (CpzeCH2eN). m/z¼274
[Mþ1]þ (FAB>0); Anal. Calcd for C15H23N5: C, 65.93; H, 8.42; N,
25.64. Found: C, 64.93; H, 7.96; N, 25.27.
4.2.3. Synthesis
of
3-[bis(1,5-dimethyl-1H-pyrazol-3-ylmethyl)
amino]propanol (6a). To a solution of acetonitrile (80 ml) con-
taining 1-hydroxymethyl-3,5-dimethylpyrazole (5.04 g, 40 mmol)
was slowly added 3-aminopropanol (1.5 g, 20 mmol) of in 20 ml of
acetonitrile. The mixture was stirred under reflux for 5 h. The sol-
vent was evaporated under reduced pressure. The reaction mixture
was extracted with dichloromethane and washed with water to
eliminate the residual amine. The organic solution was dried and
the solvent was removed under reduced pressure. Tripod 6a was
obtained in an 85% yield as a viscous oil. 1H NMR (CDCl3, 200 MHz):
Fig. 3. A schematic representation of the bivalent metal cations complexation by the
studied tripods.
A good affinity was observed with mercury, copper and lead,
however a modest affinity was observed with cadmium. The af-
finity of the prepared tripods depends on the nature of their side
chain and the best results were obtained with primary alcohol and
hydrophobic phenyl groups as side chains.
d
¼1.65 (m, 2H, CH2eCH2OH, J¼5.45 Hz); 2.10 (s, 6H, CH3Pz); 2.25 (s,
6H, CH3Pz); 2.85 (t, 2H, eNeCH2eCH2e, J¼5.7 Hz); 3.68 (t, 2H,
4. Experimental section
4.1. General methods
eCH2O, J¼5.4 Hz); 5.05 (s, 4H, NeCH2eN); 5.70 (s, 2H, PzH); 13C
NMR (CDCl3, 50 MHz):
d¼10.85 (CH3Pz); 13.25 (Pz-CH3); 35.45
(CH2eCH2O); 56.45 (NeCH2eCH2); 61.70 (CH2O); 63.55
(NeCH2eN); 105.93 (CPzH); 129.66 (CPzCH3); 132.77
(NeCPzeCH3); m/z: 292 [Mþ1]þ (FAB>0); Anal. Calcd for
C15H25N5O: C, 61.85; H, 8.59; N, 24.05. Found: C, 62.36; H, 7.96; N,
23.87.
All chemicals were reagent grade (AldricheChemical Co.) and
were used as purchased without further purification. Thin layer
chromatography was carried out on silica gel pre-coated plates
(Merck; 60 Aꢁ F254) and spots located with (a) UV light (254 and
366 nm), (b) I2 or (c) a basic solution of permanganate [KMnO4 (3 g),
K2CO3 (20 g) and NaOH (0.25 g) in water (300 ml)]. Flash column
chromatography (FCC) was carried out on Merck silica gel 60
(230e400 mesh) according to Still et al.50 1H and 13C NMR spectra
were recorded at 200 MHz with Varian spectrometers in deuterated
solvents and are reported in parts per million (ppm) with the solvent
resonance used as the internal reference. Mass spectra were de-
termined on a Platform II Micromass instrument (ESIþ, CH3CN/H2O:
50/50). Elemental analyses were performed by Microanalysis Central
Service (CNRS-France). Atomic absorption measurements were per-
formed using a double beam Varian AA 20 Spectrophotometer. The
followingintermediates: 3-hydroxymethyl-1,5-dimethylpyrazole(4)
and 3-chloromethyl-1,5-dimethylpyrazole (2) were prepared
according to the procedure described in the literature.46e48
4.2.4. Synthesis
of
1-[bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)
amino]propan-2-ol (6b). In similar procedure, 6b was obtained in
a 75% yield as a white solid. Mp: 85e87 ꢁC (C2H5OC2H5); 1H NMR
(CDCl3, 200 MHz):
d
¼1.08 (d, 3H, eCHOHeCH3, J¼6 Hz); 2.12 (s, 6H,
PzeCH3); 2.22 (s, 6H, PzeCH3); 2.75 (m, 2H, CH2eCHOH); 3.80 (m,
1H, CHOH), 4.82 (m, 4H, NeCH2eN); 5.75 (s, 2H, PzH); 13C NMR
(CDCl3, 50 MHz):
d
¼11.08 (CH3Pz); 13, 05 (Pz-CH3); 21.15
(CH3eCHO); 60.15 (CHO); 66.08 (NeCH2e); 67.05 (NeCH2eN);
107.25 (CPzH); 140.25 (CPzCH3); 148.12 (CPzCH3); m/z: 292
[Mþ1]þ (FAB>0); Anal. Calcd for C15H25N5O: C, 61.85; H, 8.59; N,
24.05. Found: C, 61.36; H, 7.86; N, 24.27.
4.2.5. Synthesis of 2-[4-[bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)
amino]phenyl}-ethanol (6c). In similar procedure, 6c was obtained

T. Harit et al. / Tetrahedron 68 (2012) 4037e4041
4041
in 80% yield as a white solid: mp: 116e118 ꢁC (C2H5OC2H5); 1H NMR
(CDCl3, 200 MHz):
References and notes
d
¼2.12 (s, 6H, PzeCH3); 2.25 (s, 6H, PzeCH3);
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2.75 (t, 2H, CH2eCH2OH); 3.80 (t, 2H, CH2eH2OH); 5.40 (s, 4H,
NeCH2eN); 5.80 (s, 2H, HPz); 5.65 (s, 2H, HPz); 6.85 (d, 2H, Hph
(m), J¼7.1 Hz); 7.10 (d, 2H, Hph (o), J¼7.2 Hz); 13C NMR(CDCl3,
50 MHz):
d
¼11.13 (CH3Pz); 13.73 (PzeCH3); 38.56 (CH2eCH2OH);
63.78 (NeCH2eN); 63.95 (CH2eCH2OH); 105.90 (CPzH); 114.91
(CPh (o)); 121.30 (CPh (m)); 126.76 (CPheCH2e); 129.88 (CPzCH3);
130.03 (NCPhe); 132.87 (NeCPzeCH3); m/z: 354 [Mþ1]þ (FAB>0);
Anal. Calcd for C20H27N5O: C, 67.98; H, 7.64; N, 19.83. Found: C,
67.15; H, 7.26; N, 20.12.
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ꢀ
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4.2.6. Synthesis
of
4-[bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)
€
amino]vinyl-1-benzene (6d). In similar procedure, 6d was obtained
in a 70% yield as a white solid. Here, the reaction mixture was
stirred to ambient temperature during 2 days. Mp: 101e103 ꢁC
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(C2H5OC2H5); 1H NMR (CDCl3, 200 MHz):
d
¼2.05 (s, 6H, PzeCH3);
2.20 (s, 6H, PzeCH3); 5.10 (d, 1H, CH]CH2); 5.50 (s, 4H,
NeCH2eN); 5.62 (d, 1H, CH]CH2); 5.75 (s, 2H, HPz); 6.62 (q, 1H,
CH]CH2); 7.05 (d, 2H, Hph (o)); 7.30 (d, 2H, Hph (m)); 13C
NMR(CDCl3, 50 MHz):
d¼10.20 (CH3Pz); 12.25 (PzeCH3); 60.35
(NeCH2eN); 105.50 (CPzH); 111.50 (CH]CH2); 119.20 (CPh (o));
126.50 (CPh (m)); 131.20 (NeCPh); 135.20 (CH]CH2); 138.50
(CPzCH3); 145.50 (NeCPz); 147.60 (CPheCH]CH2); m/z: 336
[Mþ1]þ (FAB>0); Anal. Calcd for C20H25N5: C, 71.64; H, 7.46; N,
20.90. Found: C, 72.23; H, 7.26; N, 20.18.
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4.2.7. Synthesis of N,N-bis(3,5-dimethyl-1H-pyrazol-1-ylmethyl)
propanamine (6e). In similar procedure 6e was obtained in a 78%
yield as viscous oil. 1H NMR (CDCl3, 200 MHz):
eCH2eCH3, J¼7.3 Hz); 1.46 (m, 2H, eCH2eCH3, J¼7.4 Hz); 2.42(t,
2H, NeCH2eCH2, J¼7.0 Hz); 2.08 (s, 6H, PzeCH3); 2.18 (s, 6H,
PzeCH3); 5.45 (s, 4H, NeCH2eN); 5.75 (s, 2H, HPz); 13C NMR
d
¼0.85 (t, 3H,
(CDCl3, 50 MHz):
d
¼10.80 (CH3Pz); 11.15 (eCH2eCH3); 13.15
(PzeCH3); 23.45 (NeCH2eCH2); 53.45 (NeCH2eCH2); 61.58
(NeCH2eN); 105.30 (CPzH); 139.20 (CPzCH3); 145.45
(NeCPzeCH3); m/z: 276 [Mþ1]þ (FAB>0); Anal. Calcd for
C15H25N5: C, 65.45; H, 9.10; N, 25.45. Found: C, 64.86; H, 8.96; N,
24.9.
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perature and pH remained constant for all the experiments (25 ꢁC;
pH¼7).
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Acknowledgements
Authors would like to thank CNRST (gs1) (Morocco) for financial
support.