Solventless synthesis of poly(pyrazolyl) phenyl-methane ligands and thermal transformation of tris(3,5-dimethylpyrazol-1-yl)phenylmethane

Article abstract of DOI:10.3390/molecules22030441

The solventless synthesis of tris(pyrazolyl)phenylmethane ligands of formula C₆H₅C(Pz^R2)₃ (R = H, Me), starting from PhCCl₃ and 3,5-dimethylpyrazole (Pz^Me2) or pyrazole (Pz) was performed.

Full text of DOI:10.3390/molecules22030441

molecules
Article
Solventless Synthesis of Poly(pyrazolyl)
phenyl-methane Ligands and
Thermal Transformation of
Tris(3,5-dimethylpyrazol-1-yl)phenylmethane
Edith Rodríguez-Venegas 1, Efrén V. García-Báez 1, Francisco J. Martínez-Martínez 2,
Alejandro Cruz 1 and Itzia I. Padilla-Martínez 1,
*
1
Laboratorio de Química Supramolecular y Nanociencias, Instituto Politécnico Nacional-UPIBI,
Av. Acueducto s/n Barrio la Laguna Ticomán, Ciudad de México C.P. 07340, Mexico;
edith_rove@hotmail.com (E.R.-V.); efren1003@yahoo.com.mx (E.V.G.-B.); alcralmx@yahoo.com.mx (A.C.)
Facultad de Ciencias Químicas, Universidad de Colima, Km. 9 Carretera Colima-Coquimatlán,
Coquimatlán C.P. 28400, Mexico; fjmartin@ucol.mx
2
*
Correspondence: ipadillamar@ipn.mx; Tel.: +52-555-729-6000
Academic Editor: Roman Dembinski
Received: 8 February 2017; Accepted: 6 March 2017; Published: 11 March 2017
Abstract: The solventless synthesis of tris(pyrazolyl)phenylmethane ligands of formula C6H5C(PzR2
)
3
(R = H, Me), starting from PhCCl3 and 3,5-dimethylpyrazole (PzMe2) or pyrazole (Pz)
was performed. The sterically crowded C6H5C(PzMe2
) is thermally transformed into the
3
bis(pyrazolyl)(p-pyrazolyl)phenylmethane ligand PzMe2-C6H4CH(PzMe2)2. In this compound both
PzMe2 rings are linked through the N-atom to the methine C-atom. At higher temperatures, the
binding mode of PzMe2 changes from N1 to C4. All transformations occurred via quinonoid
carbocation intermediates that undergo an aromatic electrophilic substitution on the 4-position
of PzMe2. Reaction conditions were established to obtain five tris(pyrazolyl)phenylmethane ligands
1
in moderate to good yields. H- and 13C-NMR spectroscopy and X-ray diffraction of single crystals
support the proposed structures.
Keywords: thermal synthesis; tris(pyrazolyl)phenylmethane; bis(pyrazolyl)phenylmethane;
poly(pyrazolyl)methane; three-bladed propeller; X-ray molecular structure
1. Introduction
Poly(pyrazolyl)methane ligands RR’C(Pz)2, RC(Pz)3 and C(Pz)4 are the neutral analogues of
the anionic poly(pyrazolyl)borates [1–3], where Pz can be either an unsubstituted or C-substituted
pyrazolyl unit. They are formally derived by replacing the apical borate anionic moiety [BR]−
by the isoelectronic CR group. Trofimenko, in his pioneering work in the mid-1960s, called the
poly(pyrazolyl)methane and poly(pyrazolyl)borate ligands scorpionates [
N-donor ligands that can coordinate in a mono-, bi-, or tridentate fashion to a metal center [
coordination, organometallic and related chemistry of tris(pyrazolyl)methane ligands have been
reviewed elsewhere [ ]. Bis(pyrazol-1-yl)methane ligands, [RR’C(Pz)2], have been used as synthetic
precursors to a subclass of scorpionates called heteroscorpionates [ ]. Their applications in the design
and synthesis of metal complexes with a wide range of applications have been recently reviewed [ ].
4]. They are versatile hard
5
]. The
6
7,8
8,9
Steric and electronic effects modulate the chemical properties of the corresponding coordination
and organometallic complexes of poly(pyrazol-1-yl)methane ligands. Small differences in topology,
flexibility, donor properties, modes of coordination and decomposition pathways of these ligands, can
lead to significantly different properties in their metal complexes.
Molecules 2017, 22, 441; doi:10.3390/molecules22030441
www.mdpi.com/journal/molecules

Molecules 2017, 22, 441
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Our investigations on iridium organometallic complexes formed using tris(pyrazol-1-yl)methane
indicated that the steric effect exerted by this ligand strongly determines the fate of the organic moiety
in the coordination sphere of the metal as well as the energetics of the olefinic C-H bond activation
reactions [10–12].
The chemistry of poly(pyrazolyl)methanes has been relatively underdeveloped. However, this
family of ligands can act as more than a simple spectator in the course of the chemical reactions
due to the possibility of temporary changes in denticity and its ambidentate nature after the
removal of the bridge CH proton [13]. Furthermore, the significant number of examples confirm
that the properties and reactivity of the corresponding metal complexes differ from that of the
tris(pyrazol-1-yl)borate analogues.
More recently, the use of poly(pyrazolyl)methanes in supramolecular chemistry has become more
frequent. Bis(pyrazol-1-yl)(pyridin-x-yl)methane ligands give rise to a rich variety of complexes
and supramolecular frameworks with a wide range of transition metals [14]. The crowded
tris(pyrazolyl)methane chelate in a macrobicyclic structure was synthesized in order to create a cavity
with well-defined dimensions and shape [15]. Also, aryl-o-substituted-bis(pyrazol-1-yl)methanes
(RSPhCH(PzMe2)2) have been synthesized to give rise to supramolecular microporous structures such
as coordination polymers and macrocycles [16]. Other areas of development are catalysis, bioinorganic
and biologically inspired chemistry [17]. In this field, the chemistry of Re and Tc complexes anchored
by tris(pyrazolyl)methanes have potential relevance in the field of biomedical applications, particularly
in radiopharmaceutical research [18].
In general, poly(pyrazolyl)methanes CH2(Pz)2, CH(Pz)3 and C(Pz)4 have been prepared by
treating the pyrazolate salt with CH2Cl2, CHCl3 or CCl4 in the presence of phase transfer catalysts.
This technique has been particularly exploited to prepare tris(pyrazol-1-yl)methanes of formula
HC(PzR)3 (R = 3,5-Me, 3-Ph, 3-iPr, 3-tBu, 3,5-iPr) [19
–22]. The metal catalyzed condensation of
(Pz)2E = O (E = C, S) with aldehydes or ketones provides an efficient route to unsymmetrical
tris(pyrazol-1-yl)methane ligands. However, similar chemistry is unsuccessful with substituted
pyrazolyl rings [23]. The preparation of “mixed”0 tris(pyrazolyl)methanes with two or three
0
different pyrazolyl rings (HCPzR(PzR )2 or HCPzRPzR PzR”) has been achieved by the scrambling of
tris(3,5-dimethylpyrazolyl)methane with substituted pyrazoles in acid media [24]. More recently,
a third generation of scorpionates with a substituted-aryl ring bound to the carbon bridge of
tris(pyrazol-1-yl)methane, has been synthesized starting from trifluoromethylaniline [25]. Methods for
synthesizing bis and tris(pyrazol-1-yl)methanes have been recently reviewed [26].
In an effort to contribute to the design of a new and improved synthesis of
poly(pyrazol-1-yl)methane ligands, we decided to explore the synthesis without solvent (solventless
synthesis) of tris(3,5-dimethylpyrazol-1-yl)phenylmethane (1a) and tris(pyrazol-1-yl) phenylmethane
(
1b), starting from α, ,α
α0 ”-trichlorotoluene (PhCCl3) and 3,5-dimethylpyrazole (PzMe2) or pyrazole
(Pz), (Figure 1). In this sense, thermal treatment [27] as well as sonochemical methods [28],
mechanochemistry [29], microwave [30] and infrared [31] irradiation have been used for chemical
synthesis driven by the search for new and cleaner synthetic methodologies. To the best of
our knowledge, the sterically crowded compounds 1a and 1b have never been described before,
whereas PhCCl3 has been scarcely used in spite of its similarity to CHCl3. It has been reported
as the starting material for the synthesis of the hexadentate N6-donor phenyltris[3-(2-pyridyl)
pyrazol-1-yl]methane [32].

Molecules 2017, 22, 441
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R
N
R
R
N
N
N
N
N
R
R
R
1a
R = CH3,
1b
R = H,
Figure 1. Target compounds C6H5C(PzMe2)3 (1a) and C6H5C(Pz)3 (1b).
2. Results and Discussion
2.1. Screening Reactions with PzMe2
Since the reaction of pyrazoles with PhCCl3 has been reported to occur in low yields [32], we
decided to explore the heating of 3,5-dimethylpyrazole (PzMe2) without solvent while varying several
different reaction conditions such as temperature, time, stoichiometry and the reaction atmosphere.
Results are listed in Table 1 by numbered entries as yields of the isolated products after column
chromatography. Initially, the reaction was performed in an open flask equipped with a condenser,
the PzMe2 to PhCCl3 ratio was chosen as 6:1, the excess of PzMe2 was used to trap the evolved HCl,
the mixture was melted (100 ◦C) and stirred for 10 h. A stronger base than PzMe2 was not used to
trap the evolved HCl in order to prevent the production of 1,1,2,2-tetrachloro-1,2-diphenylethane as
side-product [33]. In the above conditions, compounds
2, 5 and 6 were isolated in low yields from the
reaction mixture (entry 1) and sublimated PzMe2 was observed on the top of the flask (Scheme 1).
0
Scheme 1. Thermal reaction of 3,5-dimethylpyrazol (PzMe2) with α,α ,α”-trichlorotoluene (PhCCl3).
In order to avoid the sublimation of PzMe2 and to improve yields, we used a sealed glass ampoule
instead of a flask. The same quantities of reagents were used and heated at 120 ◦C for 24 h. In this
case, the new product
48 h, leads to only small amounts of compound
of the target compound 1a into compounds and
any of the last conditions, we carried out the reaction in two steps, the first at 80 ◦C and the second
at 120 ◦C for 24 h each. In this case compounds
(53%) and the new compound (27%) appeared as
principal products (entry 4). We tried the same reaction lowering the initial reaction time to 24 h and
the PzMe2 to PhCCl3 ratio in 8:1 and 4:1 proportions, but the yields of compounds
and were lower
appeared as oxidation products in the
4
was isolated in low yield (entry 2). The same reaction carried out at 80 ◦C for
5
(entry 3). These results suggest the transformation
. However, as compound 1a was not present in
2
4
2
3
2
3
(entries 5 and 6, respectively). In all cases, compounds
reaction mixture.
5
and
6
To avoid the formation of the oxidation products
5
and
6
, the reaction was carried out in a one-step
reaction, with a 6:1 ratio of reactants, at 80 ◦C for 24 h in a sealed ampoule under vacuum. In this
case, compound 1a was obtained as the only product in 15% yield (entry 7). The best results to obtain

Molecules 2017, 22, 441
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compound 1a in 30% yield were when the reaction was performed in the same reaction conditions
but increasing the reaction time to 48 h (entry 8). Compound 2 was isolated in 70% yield in the two
steps of temperature conditions at 80 ◦C and 120 ◦C for 48 h and 24 h, respectively (entry 9). Finally,
compound 4 was isolated in 14% yield increasing the temperature to 160 ◦C for 72 h (entry 10).
It is worth mentioning that, to the best of our knowledge, compounds 1a–4 have not been reported
before, compound
5
was reported in 1935 [34] and compound
6
is not known but the pyrazole analogue
of 6 has been reported elsewhere [35].
0
Table 1. Reaction conditions of heating 3,5-dimethylpyrazol with α,α ,α”-trichlorotoluene.
◦
Temperature ( C)/Time (h)
Products Isolated Yields (%)
Ratio 1
Entry
Vessel
Step 1
Step 2
1a
2
3
4
5
6
Open
flask
SA 2
SA
SA
SA
1
6:1
100/10
none
—
11
—
—
6
10
2
3
4
5
6
7
8
9
10
6:1
6:1
6:1
8:1
4:1
6:1
6:1
6:1
6:1
1
120/24
80/48
80/24
80/24
80/24
80/24
80/48
80/48
160/72
none
none
120/24
120/24
120/24
none
—
—
—
—
—
15
30
—
—
—
—
53
48
27
—
—
70
—
—
—
27
25
7
—
—
2
8
Trace Trace
7
6
8
9
—
—
—
—
—
—
—
—
—
—
—
14
Trace
Trace
Trace
Trace
—
—
Trace
—
SA
VSA 3
VSA
VSA
VSA
none
120/24
—
PzMe2 to PhCCl3; 2 Sealed ampoule; 3 Vacuum sealed ampoule.
2.2. Effect of Temperature and Time on the Composition of the Reaction Mixtures
In order to find the appropriate temperature that would favor one of the ligands 1a
–
4
, three
◦
reactions were performed using two temperature steps. The first step was fixed at 80 C and the second
at 100, 120 or 160 ◦C for 24 h each. In all cases, the reaction at 80 ◦C for 24 h was used as reference
with 30% composition of compound 1a. The composition of the reaction mixtures was quantified
by HPLC and the results are summarized in Table 2. These experiments and those summarized in
Table 3 were performed at a smaller scale (1/5) than the screening experiments summarized in Table 1;
thus differences in the composition of the reaction mixtures are explained because of mass dependent
conductive/convective heat transfer processes.
Table 2. Composition of the reaction mixture (%) after two heating steps at three temperatures.
◦
◦
80 C to T2 ( C)
120
Comp.
100
160
1a
2
3
26
11
0
18
55
12
0
0
0
0
4
0
11
◦
3 are formed at 100 and 120 C,
From the above results, it can be concluded that compounds
respectively, at the expense of compound 1a. Compound
low quantity. These results suggest that compound 1a is successively transformed into compounds
with the increase in the temperature of reaction, accompanied by extensive decomposition at 160 ◦C.
As expected, compounds 1a and , with C-N bonds, are produced at lower temperatures; on the
2
and
4
remained at 160 ◦C as the only product in
2–4
2
contrary, compounds 3 and 4, with C-C bonds, are favored at higher temperatures.
◦
In an independent experiment, the temperature was fixed at 120 C but the course of the reaction
was monitored by HPLC for three days. The daily percent composition of the reaction mixture

Molecules 2017, 22, 441
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◦
is listed in Table 3. A mixture of compounds 1a
–
4
was found the first day of reaction at 120 C.
In the next two days, the composition of the mixture showed an increase in compound
corresponding decrement of compounds 1a . These results confirm that once formed, compounds
are consecutively transformed into compound 4.
4 with the
–3
1–3
◦
Table 3. Composition of the reaction mixture (%) after heating at 120 C.
Heating Time (Days)
Comp.
1
2
3
1a
2
3
13
7
5
8
0
3
0
0
0
4
23
35
40
Compounds
be used as monomers for new polyamines or ligands for the synthesis of MOF’s [36]. In addition,
both nitrogen atoms of each pyrazole ring in compound are available for further coordination.
2–4 contain a built-in entry point for further functionalization, and they could
4
Suzuki coupling methodology starting from 1-trityl-1H-pyrazol-4-ylboronate pinacol esters and
brominated aromatic precursors has been used to achieve this structural feature in the synthesis
of oligo-(1H-pyrazol-4-yl)-arenes [37].
2.3. Reaction between PhCCl3 and Pz
The reaction of pyrazole and PhCCl3 was performed using the reaction conditions described in
entry 9 of Table 1. In these conditions, tris(pyrazolyl)phenylmethane 1b was isolated in 50% yield
as the only product, Scheme 2. Due to the absence of more products, no other reaction conditions
were tested.
0
Scheme 2. Thermal reaction of pyrazole with α,α ,α”-trichlorotoluene.
2.4. Stucture by NMR and IR
Compounds 1a and 1b possess C3 symmetry in agreement with three pyrazole rings bonded to
the bridge carbon atom of the former PhCCl3. This was confirmed by the 1H-NMR spectrum of 1a that
shows two signals for each of methyl groups (δ 2.18, 1.62). One of them appears shielded by 0.4 ppm
δ δ 5.95.
compared with that of (PzMe2)CH ( 2.09, 2.03) [21]. The CH of three PzMe2 rings appeared at
Compound 1b shows the signals for Pz-ring protons at
δ 7.73 (d), 7.52 (d) and 6.36 (t). The typical 1:2:2
pattern for a monosubstituted benzene ring is present in the 1H-NMR spectra of both compounds.
Finally, the bridge carbon atom is at δ 94.3 and 94.4 in 13C-NMR for 1a and 1b, respectively.
The 1H-NMR spectrum of compound
2
shows two sets of signals at
in a 2:1 proportion corresponding to the methyl groups of the PzMe2 rings. Two pyrazole CH are at
5.86 and 5.98 ppm in agreement with a molecule with C2v symmetry. The methine proton and carbon
δ 2.28, 2.27 and 2.26, 2.20 ppm
δ

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atoms appear as a singlet at
δ
7.65 (1H) and
δ
73.5 (13C), very similar to those values reported for
(PzMe2)2CHPh [26]. In addition, the presence of signals at
δ 7.40 and 6.98, as doublets, are in agreement
with the typical pattern for a p-substituted benzene ring. They were assigned to the m- and o-protons,
respectively, by NOE effect when irradiating the bridge methine CH. This pattern is also observed for
compounds 3 and 4 with similar chemical shifts.
The symmetry is lost in compound
methine carbon atom. The C-N bonded PzMe2 ring, shows signals at
respectively. No signal corresponding to H4 was observed and C4 of PzMe2 ring appeared at
as singlet in the 13C{1H} NMR spectrum of the C-C bonded ring. In addition, a broad singlet at
144.0, corresponding to the Me carbon atom of the two tautomers in equilibrium, was observed; the
respective NH appeared at 7.60. Also, a singlet appeared for each remaining four methyl carbon
atoms. It is worth noting that the chemical shifts of the methine proton and carbon atoms are at 6.45
and 57.0, respectively a value in the middle of the corresponding values for compounds 2 and 4.
In compound
, both PzMe2 rings are linked by a C-C bond to the bridge methine carbon atom.
Some relevant changes in both the 1H- and 13C-NMR spectra are appreciated in agreement with its
C2v symmetry. The CH of the pyrazole ring is absent in the 1H-NMR spectrum, a broad signal at
12 for the NH proton appears instead, as well as a singlet at
115.7 in the 13C{1H} NMR spectrum,
corresponding to C4 of both PzMe2 rings. Tautomeric equilibrium, typical of NH pyrazole heterocycles,
is present leading to a broad signal for both 142.7. Finally, the
Me carbon atoms of each PzMe2 at
bridge methine proton and carbon atoms are shifted to high fields (δ 5.3, 39.3).
The 1H-NMR spectrum of compound
shows the characteristics set of signals corresponding to a
monosubstituted benzene ring as well as a singlet at 6.06 and two signals in 2.63 and 2.25 for two
methyl groups of the PzMe2 ring. The signal at 168.7 in the 13C-NMR spectrum was assigned to a C=O
group which was confirmed by the presence of an IR stretching band at 1694 cm−1. These spectroscopic
data are in agreement with an amide group. The NMR of compound shows the characteristic signal
for an aldehyde: a singlet at
10.04 in the 1H-NMR spectrum, and at 191.4 in the 13C-NMR one.
3
because the PzMe2 rings are bonded differently to the bridge
5.86 and 105.8 for H4 and C4,
113.6
δ
δ
δ
C
δ
δ
4
δ
δ
C
δ
5
δ
δ
δ
6
δ
δ
The stretching frequency at 1697 cm−1 confirmed the presence of the C=O group. The signals in the
1H-NMR spectrum are consistent with the presence of a p-substituted benzene ring at
and, three singlets at δ 6.06, 2.41 and 2.31 for the PzMe2 ring.
δ 7.97 and 7.67
2.5. Proposed Reaction Mechanism
Based on the above results a mechanistic pathway is proposed for the heating reaction of PzMe2
+
and PhCCl3. A nucleophilic attack of two PzMe2 molecules to carbocation PhCCl2 formed from
PhCCl3, give the intermediate carbocation
I
. The fate of carbocation
80 C, the attack of the third PzMe2 leads to compound 1a (Scheme 3, path A). Compound 1a reversibly
releases one pyrazole ring to regenerate carbocation
when temperature is increased to 100 ◦C. Then,
compound
is obtained by the attack of the third PzMe2 to the resonance quinonoid aryl carbocation
I depends on temperature, at
◦
I
2
intermediate II (Scheme 3, path B) loosing of one proton to recover the aromatic form. The intrinsic
instability of compound 1a could be attributed to the steric repulsion exerted by both phenyl and
methyl groups, which favors the breaking of the bridge C-N bond to liberate the steric constraint.
α
-chlorobenzyl cations have been reported as intermediates in reactions of hydrolysis [38] whereas
radicals or cation radicals are produced only when initiators are added [39].

Molecules 2017, 22, 441
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Scheme 3. Proposed mechanistic pathway for the reaction of PzMe2 and PhCCl3.
The synergy of both steric and electronic effects is evident in the reaction of the unsubstituted
pyrazole (Pz) and PhCCl3 that produce the stabile compound 1b as the only product. No decomposition
or transformation of 1b was observed at the temperature of 120 ◦C. Pyrazole is non-steric constrained
and less basic than PzMe2 (pKa values are 2.85 and 14.2 for Pz, 4.28 and 15.1 for PzMe2) [40
,
41].
. Their formation implies the substitution of
N-bonded PzMe2 by C-bonded PzMe2. At 120 ◦C, compound
irreversibly releases one protonated
Compounds
3 and 4 are produced from compound 2
2
pyrazole ring. This step requires the participation of an electron donating group in the aryl ring
to weaken the C-N bond via the formation of the quinonoid carbocation intermediate III, which
is stabilized by resonance. The intermediate resonance hybrid form IV performs an aromatic
electrophilic substitution (AES) on the 4-position of PzMe2 to form compound
3. The subsequent
elimination-substitution of the second pyrazole leads to the formation of compound (Scheme 4). The
4
activating role of the electron donating group in the aryl ring have been demonstrated to be necessary
in an elimination-addition mechanism that provides access to tris(pyrazolyl)-toluidines [25]. On the
other hand, AES reaction in PzMe2 is reported to occur under mild conditions [42].
Scheme 4. Proposed mechanistic transformation of compound 2 to 3 and 4.
2.6. Single Crystal Structures of 1a–b and 2
The structures of compounds 1a and 1b were unambiguously confirmed by single-crystal
X-ray diffraction analysis. Suitable crystals of compound 1a were obtained from hexane solution.
Compound 1a crystallized in the monoclinic system with a space group P21/c. The molecular structure
is displayed in Figure 2.

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Figure 2. ORTEP perspective of compound 1a at 30% probability level, hydrogen atoms are omitted
for clarity. Selected bonds lengths (Å) and angles (◦): N10-C1 1.4657(19), N20-C1 1.4725(18),
N30-C1 1.479(2), C1-C2 1.532(2), N30-C1-C2 111.47(11), N20-C1-C2 107.84(11), N30-C1-C2 111.75(11),
N10-C1-N20 109.86(11), N10-C1-N30 106.48(12), N20-C1-N30 109.43(11), N11-N10-C1 119.04(11),
N21-N20-C1 118.72(11), N31-N30-C1 119.76(11).
The geometry around the C1 bridge carbon atom is nearly tetrahedral with an average N-C-N
bond angles of 109(2)◦ and the N-C-CPh angle of 110(2)◦. The mean C-N and C-CPh bond distances
of 1.477(7) Å and 1.532(2) Å, respectively, are in close correspondence with single bonds (1.493(20),
1.513(14) Å) [43]. The three PzMe2 rings adopt a three-bladed propeller structure around the axial
phenyl with R3-C-N-N torsion angles of
helical molecules of 1a are found to exist as both left-(
±
8.97(17)◦,
±
101.46(15)◦ and
±
141.34(13)◦. Thus, racemic
)-enantiomers in the
Λ
) and right-handed (
∆
asymmetric unit of the crystal lattice. Among several possible conformers, compound 1a adopts a sp,
ac, ac conformation (synperiplanar (sp), synclinal (sc), antiperiplanar (ap) and anticlinal (ac)).
Suitable crystals of compound 1b were obtained from a saturated solution in AcOEt. Crystals of
1b crystallize in the orthorhombic system in the acentric P212121 space group. The molecular structure
is displayed in Figure 3. Bond distances and angles are very similar to those found in compound 1a
(average values): N-C-N bond angle of 110(2)◦, N-C-CPh angle of 111(2)◦ and C-N and C-CPh bond
distances of 1.476(16) Å and 1.525(5) Å, respectively. Three blades are formed by Pz rings; the values
of the R3-C-N-N torsion angles are ±87.17(4)◦ (sc), ±104.2(4)◦ (ac) and ±166.6(4)◦ (ap).
Figure 3. ORTEP perspective of compound 1b at 25% probability level; hydrogen atoms are omitted for
◦
clarity. Selected bonds lengths (Å) and angles ( ): N10-C1 1.472(5), N20-C1 1.452(5), N30-C1 1.477(5),
C1-C2 1.525(6), N30-C1-C2 111.8(3), N10-C1-N20 109.9(3), N10-C1-N30 107.8(3), N11-N10-C1 119.1(3),
N21-N20-C1 120.8(4), N31-N30-C1 126.2(4)

Molecules 2017, 22, 441
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Since the structures of several ligands
7–
15, similar to compounds 1a and 1b, have been
reported [24,25,44–50], a brief comparison between them seems to be appropriate. The structures,
R3-C-N-N torsion angles values and the conformation of pyrazole rings in compounds 1a
,b and 7–15
are listed in Table 4.
Table 4. Torsion angles and conformation of three bladed propeller structures of general formula
(PzR1R2)3CR3
.
◦
Comp.
Substituents
Torsion Angle ( ) R3CNN
PzR1R2 Conformation 1
R1 = R2 = CH3, R3 = C6H5
R1 = CH3, R2 = C6H5, R3 = H
R1 = R2 = CH3, R3 = H
1a
7 [44]
8 2 [45,46]
1b
−8.97(17), 101.46(15), 141.34(13)
−18.3, 133.4, 148.6
sp, ac, ac
sp, ac, ac
sp, ac, ap
sc, ac, ap
sp, sc, ap
sp, sc, ap
sc, sc, ap
sc, sc, ap
sc, sc, ap
sp, sp, ap
sp, sp, ap
(±)25(5), (±)116(5), (±)152(5)
−87.2(4), −104.2(4), −166.6(4)
29.89(13), 87.54(11), 179.85(9)
−25(11), −83(14), 173(7)
42.6(7), 73.6(8), 166.4(2)
R1 = R2 = H, R3 = C6H5
R1 = R2 = H, R3 = o-C6H4-NH2
R1 = R2 = H, R3 = p-C6H4-NH2
R1 = R2 = H, R3 = p-C6H4-C6O2S
R1 = R2 = H, R3 = p-C6H4OH
R1 = R2 = H, R3 = CH2OH
R1 = H, R2 = CH3, R3 = H
R1 = R2 = R3 = H
9 [25]
10 [25]
11 [47]
12 [48]
13 [49]
14 [24]
15 [50]
1
−45.02(14), −68.86(14), 173.04(14)
−34.49(13), −62.50(12), 174.56(9)
24.48, 27.97, 170.87
13.6, 15.7, 176.0
Torsion angle from 0◦ to
±
30◦ is called synperiplanar (sp),
±
30◦ to
±
90◦ synclinal (sc),
±
90◦ to
±
150◦ anticlinal
(ac) and ±150◦ to ±180◦ antiperiplanar (ap). Average value of two molecules in the asymmetric unit.
2
All these molecules are very similar; their bond distances and angles have no evident differences
regardless of the steric demand from the substituents in the pyrazole ring or in the apical carbon
atom. However, steric effects seem to determine the conformation adopted by pyrazole rings in the
three-bladed propeller structure. Compounds 1a and 7, the most crowded, are in such disposition
that one pyrazole is in sp and the other two are in ac conformations (sp + 2ac). As long as steric
demand is diminished, one ring adopts an ap conformation and the other two are concomitantly
twisted to finally adopt the sp conformation (2sp + ap) in the less crowded compounds 14 and 15
As expected, substituents in the pyrazole rings exert more steric demand than those located in the
apical carbon atom.
.
Compound
2 crystalized with 0.5 molecules of water in the asymmetric unit as a monoclinic
system with a space group C2/c. The crystal structure is shown in Figure 4. Bond distances and angles
are very similar to those◦found in compound 1a (average values): N-C-N bond angle of 111.5(3)◦,
N-C-CPh angle of 113.3(4) and C-N and C-CPh bond distances of 1.455(7) Å and 1.521(5) Å, respectively.
Two blades are formed by PzMe2 rings, the values of the R3-C-N-N torsion angles are
−
105.0(3)◦ and
−29.2(5)◦ corresponding to ac, sp conformation, respectively.
Two molecules of
2 are hydrogen bonded to one molecule of water. One of them forms a pseudo
six membered ring R22(6) [51] through strong O-H···N interactions, with the participation of pyrazole
N atom as the acceptor and by soft C(sp3)-H···O interactions. The other molecule of
2 is linked to
the oxygen atom of the water molecule by pyrazole C4-H as donor (Figure 5). This supramolecular
arrangement highlights the acid-base sites in the molecule, in agreement with the proposed mechanism
of transformation of compound 2 into compounds 3 and 4 (vide supra).

Molecules 2017, 22, 441
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Figure 4. ORTEP perspective of compound 2 at 25% probability level, hydrogen atoms and the molecule
of water are omitted for clarity. Selected bonds lengths (Å) and angles (◦): N10-C1 1.464(5), N20-C1
1.445(5), C1-C2 1.521(5), N10-C1-C2 112.5(3), N20-C1-C2 114.1(3), N10-C1-N20 111.5(3), N11-N10-C1
116.7(3), N21-N20-C1 121.4(3).
Figure 5.
Supramolecular structure of compound
2
.
Geometry of hydrogen bonding:
H1A···N11 = 1.96(6) Å, O1···N11 = 2.925(4) Å, O1-H1A···N11 = 156(6)◦ and H1···O1 = 2.51 Å,
1
C1···O1 = 3.441(6) Å, C1-H1···O1 = 137◦ (symmetry code =
−
1/2 + x, + y, z); H33···O1 = 2.51 Å,
2
◦
C33···O1 = 3.410(6) Å, C33-H33···O1 = 158 (symmetry code = x, −1 + y, z).
3. Materials and Methods
3.1. Chemicals
Pyrazole, 3,5-dimethylpyrazole,
used as received.
α, ,α”-trichlorotoluene and solvents were reagent grade and
α0
3.2. Instrumental Methods
Melting points were measured on an IA 9100 apparatus (Electrothermal, Staffordshire, UK) and are
uncorrected. IR spectra were recorded using a 3100 FT-IR Excalibur Series spectrophotometer (Varian,
Randolph, MA, USA) equipped with an ATR system. Mass spectra were obtained in a 3900-GC/MS
system (Varian, Palo Alto, CA, USA) with an electron ionization mode. Elemental analyses (EA) were

Molecules 2017, 22, 441
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performed on a 2400 elemental analyzer (Perkin-Elmer, Waltham MA, USA). 1H- and 13C-NMR spectra
were recorded on a Varian Mercury 300 (1H, 300.08; 13C, 75.46 MHz) instrument in CDCl3 solutions for
compounds 1–6, and in DMSO-d6 solutions for compound 7, SiMe4 as the internal reference was used.
Chemical shifts are in ppm and nJ(H-H) in hertz. The chemical shift assignments were performed on
the basis of 1H- and 13C-NMR NOE, COSY and HETCOR experiments. Composition of the reaction
mixtures were performed in a Varian 9010 HPLC instrument at 252 nm. A C18 column of 5 µm particle
size and 25 cm length and 0.5 cm wide was used. Elution was achieved with MeOH/H2O mixtures in
a 7:3 proportion, unless otherwise specified.
3.3. X-ray Diffraction Methods
Single-crystal X-ray diffraction data of molecules 1a
CMOS (Bruker, Karlsruhe, Germany) or Nonius Kappa (Rotterdam, The Netherlands) area detector
diffractometers with Mo K radiation, = 0.71073 Å. A table listing the crystallographic data
, 1b and 2 were recorded on a D8 Quest
α
λ
is provided as Supplementary Material. The structures were solved by direct methods using
SHELXS97 [52] program of WinGX package [53]. The final refinement was performed by full-matrix
least-squares methods on F2 with SHELXL97 [52] program. H atoms on C were geometrically
positioned and treated as riding atoms, with C-H = 0.93–0.98 Å, and with Uiso(H) = 1.2Ueq(C).
The hydrogen atoms of the water molecule were found by Fourier difference and freely refined. The
program Mercury was used for visualization, molecular graphics and analysis of crystal structures [54].
The software used to prepare material for publication was PLATON [55]. Crystallographic data for
the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication CCDC numbers 1527853 (1a), 1527852 (1b) and 1527854 (2). Copies of the
data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(Fax: +44-01223-336033 or E-Mail: deposit@ccdc.cam.ac.uk). Crystals suitable for X-ray analysis were
obtained from the saturated hexane solution of compound 1a and from DMSO-H2O solution (1:1) of
compound 1b. Compound
2 slowly crystalized with one molecule of water in the asymmetric unit
from the semi-solid remaining after solvent evaporation.
Crystal Data for C22H26N6 1a, M = 374.5 g/mol): monoclinic, space group P21/c (No. 14),
a = 10.0680(3) Å, b = 14.6640(3) Å, c = 15.3674(5) Å,
T = 298(2) K, Dcalc = 1.200 g/cm3, 23332 reflections measured (3.4◦
(
β
= 114.204(3)◦, V = 2069.35(31) Å3, Z = 4,
≤
2
Θ ≤ 27.5◦), 4632 unique
(Rint = 0.046, Rsigma = 0.048) which were used in all calculations. The final R1 was 0.053 (I > 2
and wR2 was 0.125 (all data).
σ(I))
Crystal Data for C16H14N6 (1b, M = 290.33 g/mol): orthorhombic, space group P212121 (No. 19),
a = 7.0198(8) Å, b = 14.2693(16) Å, c = 14.6994(17) Å,
α = β = γ
= 90◦, V = 1449.37(3) Å3, Z = 4,
T = 293(2) K, Dcalc = 1.331 g/cm3, 8182 reflections measured (2.0◦
≤
2
Θ ≤ 24.0◦), 2280 unique
(Rint = 0.08, Rsigma = 0.139) which were used in all calculations. The final R1 was 0.055 (I > 2
wR2 was 0.1203 (all data).
σ(I)) and
Crystal Data for C22H26N6
a = 20.9571(15) Å, b = 9.5425(6) Å, c = 21.8515(16) Å,
T = 100(2) K, Dcalc = 1.200 g/cm3, 19257 reflections measured (2.4◦
(Rint = 0.043, Rsigma = 0.0351) which were used in all calculations. The final R1 was 0.089 (I > 2
and wR2 was 0.188 (all data).
·
0.5H2O (2, M = 383.49 g/mol): monoclinic, space group C 2/c (No. 15),
β
= 103.528(2)◦, V = 4248.69(22) Å3, Z = 4,
≤
2
Θ ≤ 25.0◦), 3584 unique
σ(I))
3.4. Synthetic Procedures
3.4.1. Open Flask Procedure
3,5-Dimethylpyrazole (PzMe2, 5.00 g, 52.0 mmol) was placed in a round bottom flask, submerged
◦
in a silicon oil bath and heated at 110 C with constant stirring. When the pyrazole was molten,

Molecules 2017, 22, 441
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α
,
α0
,
α
”-trichlorotoluene (PhCCl3, 246
µL) was added dropwise every hour until complete 1.230 mL
(8.660 mmol) had been added. Heating was maintained for 5 h to obtain a yellow viscous liquid. The
products were purified by column chromatography on silica gel using a 6:4 mixture of hexane/EtOAc
as eluent (Table 1, entry 1).
3.4.2. Sealed Ampoule Procedure
PzMe2 (5.00 g, 52.0 mmol) was ground in a mortar and placed into a 10 mL glass ampoule with
PhCCl3 (0.93 mL for 8:1; 1.23 mL for 6:1 or 1.85 mL for 4:1 ratio). The ampoules were sealed at
room temperature, introduced into a convection oven and allowed to react at the temperature and
time indicated in Table 1. The obtained viscous brown colored mixtures were dissolved in 50 mL of
CHCl3 to remove them from the ampoules and subjected to column chromatography on silica gel.
Compounds
as eluents.
1–3 and 5–6 were purified using hexane/EtOAc mixtures from 8:2 to 6:4 proportions
3.4.3. Vacuum Sealed Ampoule Procedure
PzMe2 (5.00 g, 52.0 mmol) was ground in a mortar and placed into a 10 mL glass ampoule with
PhCCl3 (1.23 mL, 8.66 mmol, 6:1). The ampoules were frozen at
then introduced into a convection oven and allowed to react at the temperature and time indicated in
Table 1. The reaction mixtures were treated as indicated in Section 3.4.2.
−
30 ◦C, sealed under vacuum and
3.5. Synthesis of Compounds 1–6
1,10,1”-(Phenylmethanetriyl)tris(3,5-dimethyl-1H-pyrazole) (1a). This compound was synthesized
following the procedure described in Section 3.4.3 heating at 80 ◦C for 24 h (Table 1, entry 8) to obtain
0.975 g (2.60 mmol, 30% yield) of a white crystalline solid m.p. = 90 ◦C after column chromatography.
1H-NMR (CDCl3):
δ
7.39 (t, 1H, 3J = 6.9, H-10), 7.32 (t, 2H, 3J = 7.0, H-9), 7.02 (d, 2H, 3J = 7.0, H-8),
146.9 (C-3), 143.9 (C-5), 138.1
5.95 (s, 3H, H-4), 2.18, 1.62 (s, 9H each, 6CH3). 13C-NMR (CDCl3):
δ
(C-7), 130.5 (C-8), 129.6 (C-9), 127.3 (C-10), 109.1 (C-4), 94.3 (C-6), 14.3, 12.9 (CH3). IR neat (cm−1):
1697 (C=C), 1562 (Car), 1450, 1411, 1374, 1316, 1027, 890, 716. EA % found [calculated for C22H26N6
(374.49 g·mol−1)]: 70.06 (70.56, C), 7.11 (7.00, H), 22.01 (22.40, N).
0
◦
1,1 ,1”-(Phenylmethanetriyl)tris(1H-pyrazole) (1b). A crystalline solid m.p. = 105 C was obtained (1.95 g,
55% yield), starting from 4.97 g (17.16 mmol) of pyrazole and 1.7 mL (12.2 mmol) of PhCCl3. Procedure
3.4.3 was followed using two temperature steps: 80 ◦C and 120 ◦C for 48 and 24 h each, respectively
(Table 1, entry 9). The crude product was solubilized in EtOAct and filtered, whereupon compound
1b crystallized from the solution. H-NMR (CDCl3): 7.73 (d, 3H, H-3), 7.52 (d, 3H, 4J = 2.6, H-5), 7.48
1
(t, 1H, 3J = 7, H-10), 7.41 (t, 2H, 3J = 8.7, H-9), 7.09 (d, 2H, 3J = 8, H-8), 6.36 (t, 3H, 4J = 2.6, 1.7, H-4).
13C-NMR (CDCl3): 141.6 (C-3), 137.6 (C-7), 132.6 (C-5), 130.8 (C-10), 128.9 (C-9), 128.5 (C-8), 106.7 (C-4),
93.4 (C-6). IR (neat,
EA % found [calculated for C16H14N6 (290.32 g
ν
/cm−1): 1682 (C=N), 1451, 1419, 1388, 1196, 1095, 1087, 864, 746 (Pz out of plane).
·
mol−1)]: 66.16 (66.19, C), 4.91 (4.86, H), 28.91 (28.95, N).

Molecules 2017, 22, 441
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14
15
14
14
13
13
13
15
15
N
N
N
N
N
10
N
10
10
9
8
9
8
9
8
7
7
7
6
6
6
3
18
N
N
3
3
N
N
N
19
4
N
N
H
N
N
N
N
N
5
5
5
20
4
4
H
H
2
3
4
1,10-((4-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole) (
2). Synthesized
following the procedure described in Section 3.4.3 using two temperature steps at 80 ◦C and
◦
120 C for 48 and 24 h each, respectively (Table 1, entry 9). After column chromatography, 2.28 g
(6.09 mmol, 70% yield) of compound◦
2
as a viscous yellow liquid which slowly solidified after
7.65 (s, 1H, H-6), 7.40 (d, 2H,
standing as a yellow solid m.p. = 97 C was obtained. 1H-NMR:
δ
3J = 8.8, H-9), 6.98 (d, 2H, 3J = 8.8, H-8), 5.98 (s, 1H, H-14), 5.86 (s, 2H, H-4), 2.28, 2.27 (s, 6H each, 4CH3),
2.26, 2.20 (s, 3H each, 2CH3). 13C-NMR:
149.5 (C-13), 148.8 (2C-3), 141.3 (2C-5), 140.1 (C-15), 139.7
(C-10), 135.8 (C-7), 127.9 (2C-8), 124.6 (2C-9), 107.5 (C-14), 107.2 (2C-4), 73.5 (C-6), 13.9, 13.0 (4CH3),
13.7, 12.7 (2CH3). IR (neat,
/cm−1): 1612 (C=N), 1556 (C=C), 1520 (Car), 1417 (CH3), 750 (pyrazole out
δ
ν
of plane). MS (%): 374.0 (M+, 3), 279.0 (100), 183.9 (5), 162.0 (26), 94.8 (12.5). EA % found [calculated
for C22H26N6 (374.48 g·mol−1)]: 70.50 (70.56, C), 7.17 (7.00, H), 21.70 (22.44, N).
1,40-((4-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole) (
3). Synthesized
following the procedure described in Section 3.4.2 using two temperature steps of 80 ◦C and 120 ◦C
for 24 h each (Table 1, entry 4) to obtain, after column chromatography, 0.88 g (2.35 mmol, 27% yield)
of a yellow viscous liquid that after a while turned into a beige solid, m.p. = 126 ◦C. 1H-NMR:
δ
7.60
(b, 1H, NH), 7.31 (d, 2H, 3J = 8.5, H-9), 6.91 (d, 2H, 3J = 8.5, H-8), 6.45 (s, 1H, H-6), 5.96 (s, 1H, H-14),
5.86 (s, 1H, H-4), 2.27, 2.25, 2.20, 2.18 (s, 3H each, 4CH3), 1.92 (s, 6H, 2CH3). 13C-NMR:
149.2 (C-13),
δ
147.9 (C-3), 144.0 (C-18,20), 140.0 (C-15), 139.7 (C-5), 139.6 (C-10), 139.0 (C-7), 127.9 (2C-8), 124.8 (2C-9),
113.6 (C-19), 107.2 (C-14), 105.8 (C-4), 57.0 (C-6), 14.0, 13.7, 12.7, 11.5 (4CH3), 11.8 (2CH3). IR (neat,
ν
/cm−1): 1613, 1589 (C=N), 1554 (C=C), 1519 (Car), 1425 (CH3), 749 (pyrazole out of plane). MS (%):
374.0 (M+, 3), 279.0 (100), 94.8 (67.5). EA % found [calculated for C22H26N6 (374.48 g
(70.56, C), 7.10 (7.00, H), 21.82 (22.40, N).
·
mol−1)]: 70.20
4,40-((4-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)methylene)bis(3,5-dimethyl-1H-pyrazole) (
4). Synthesized
following the procedure described in Section 3.4.3 after heating at 160 ◦C for 72 h (Table 1, entry 10).
Excess PzMe2 was sublimed and the remaining solid was stirred twice in 25 mL of 10% NaHCO3
solution, decanted, washed twice with 50 mL of water, filtered and air dried. After column
◦
chromatography, 0.460 g (1.23 mmol, 14% yield) of a pale beige solid which decomposes at 249 C was
isolated. H-NMR:
δ
12.0 (b, 2H, NH), 7.38 (d, 2H, 3J = 8.0, H-9), 7.13 (d, 2H, 3J = 7.4, H-8), 6.03 (s, 1H,
1
H-14), 5.3 (s, 1H, H-6), 2.24, 2.15 (s, 3H each, 2CH3), 1.72 (b, 12H, 4CH3). 13C-NMR:
142.7 (b, 2C-5 and 2C-3), 142.6 (C-7), 139.7 (C-15), 138.2 (C-10), 129.6 (2C-8), 124.5 (2C-9), 115.7 (2C-4),
107.6 (C-14), 39.3 (C-6), 14.0, 12.8 (2CH3), 11 (b, 4CH3). IR (neat,
/cm−1): X (C=N), 1558 (C=C), 1517
δ 148.3 (C-13),
ν
(Car), 1413 (CH3), 760 (pyrazole out of plane). EA % found [calculated for C22H26N6 (374.48 g
69.41 (70.56, C), 7.03 (7.00, H), 21.52 (22.40, N).
·
mol−1)]:

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(3,5-Dimethyl-1H-pyrazol-1-yl)(phenyl)methanone (
0.173 g (6%) of a yellow viscous liquid, after column chromatography. H-NMR:
5
). Synthesized following the procedure 3.4.1 to afford
1
δ
8.00 (d, 2H, 3J = 8.0,
H-8), 7.56 (t, 1H, 3J = 7.5, H-10), 7.46 (t, 2H, 3J = 7.4, H-9), 6.06 (s, 1H, H-4), 2.63, 2.25 (s, 3H each, 2CH3).
13C-NMR:
168.7 (C-7), 152.4 (C-3), 145.3 (C-5), 132.7 (C-10), 131.6 (C-8), 128.1 (C-9), 111.4 (C-4), 14.6,
14.1 (2CH3). IR (neat,
/cm−1): 1694 (C=O), 1583 (C=C), 1448 (CH3). MS (%): 200.9 (M+, 7.5), 172.0
δ
ν
(11.3), 104.9 (100), 76.9 (45.0), 51.0 (20).
4-(3,5-Dimethyl-1H-pyrazol-1-yl)benzaldehyde (
6
). Synthesized following procedure 3.4.1 to afford 0.343 g
1
(10%) of a yellow viscous liquid after column chromatography. H-NMR:
δ
10.04 (s, 1H, CHO), 7.97
3
3
(d, 2H, J = 8.34, H-8), 7.67 (d, 2H, J = 8.1, H-7), 6.06 (s, 1H, H-4), 2.41, 2.31 (s, 3H each, 2CH3).
13C-NMR:
191.4 (C-10), 150.5 (C-9), 145.0 (C-5), 140.0 (C-6), 134.5 (C-3) 130.9 (C-8), 124.1 (C-7), 108.9
(C-4), 13.8, 13.2 (2CH3). IR (neat,
/cm−1): 1697 (C=O), 1555 (C=C), 1514 (Car), 1418 (CH3). MS (%):
δ
ν
200.3 (M+, 27.5), 199.9 (100), 170.9 (11.3), 129.9 (17.5), 76.9 (20).
3.6. Temperature Effects Experiments
Four ampoules containing 1.000 g of PzMe2 (10.4 mmol), previously ground in a mortar, and
0.250 mL of PhCCl3 (1.7 mmol) each were cooled at −30 ◦C and sealed under vacuum. The reference
ampoule was introduced into a preheated oven at 80 ◦C and heated at the same temperature fo◦r 24 h.
The other three ampoules were heated in two steps of temperature at 80/100, 80/120 and 80/160 C for
24 h at each temperature. The obtained viscous reaction mixtures were dissolved in 30 mL of CHCl3 to
homogenize and the solvent was evaporated to dryness, except the last ampoule whose content was
homogenized by grinding it in a mortar. Samples of 10 mg/mL in methanol as solvent were prepared
and then diluted to achieve 2.5 mg/mL for HPLC measurements. Chromatograms were recorded with
10 µL of each sample eluted in the same conditions as the calibration curve. Calibration curves were
obtained from methanol solutions of 2.0, 1.5, 1.0 and 0.5 mg/mL of compounds 1a–4 each.
3.7. Time Effect Experiments
Three ampoules were prepared as described for temperature effects but starting with 5.00 g of
PzMe2 (52.0 mmol) and 1.23 mL of PhCCl3 (8.66 mmol) each, and heated in an oven at 120 ◦C for one,
two and three days. The samples for HPLC were prepared as before.
4. Conclusions
In summary, the solventless synthesis of tris(pyrazolyl)phenylmethane ligands C6H5C(PzR2
)
3
(R = H, Me), starting from PhCCl3 and 3,5-dimethylpyrazole (PzMe2) or pyrazole (Pz) was
achieved. The sterically crowded C6H5C(PzMe2)3 is labile due to both steric and electronic reasons;
therefore it is thermally transformed at 120 ◦C into bis(pyrazolyl)(p-pyrazolyl)phenylmethane ligand,
PzMe2-C6H4CH(PzMe2)2. In this compound both PzMe2 rings are linked through the N-atom to the
methine-bridge C-atom. At longer times of reaction or at temperatures beyond 120 ◦C, the binding
mode of PzMe2 changes from N1 to C4. Reaction conditions were established to obtain compound 1a
in 30%, 1b in 55%,
2 in 70%, 3 in 27% and 4 in 14% yields. The structures were proposed on the basis of

Molecules 2017, 22, 441
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1H- and 13C-NMR spectroscopy and single crystal X-ray diffraction. The three PzMe2 rings, in
compounds 1a and 1b, adopt a three-bladed propeller structure around the axial phenyl ring.
Comparison to the structures of other tris(pyrazolyl)phenylmethane ligands allowed to conclude
that steric effects determine the conformation adopted by pyrazole rings: (sp + 2ac) in the most
crowded and (2sp + ap) in the less crowded compounds. Substituents in the pyrazole rings exert more
steric demand than those located in the apical carbon atom.
Supplementary Materials: Supplementary materials are available online.
Acknowledgments: This work was supported by CONACYT grant 2551354, SIP-IPN grant 20160261 (Secretaría
de Investigación y Postgrado del Instituto Politécnico Nacional), CGIC-UC (Coordinación General de Investigación
Científica de la Universidad de Colima) and PROMEP-SEP. Authors thanks María de Jesús Rosales-Hoz for the
X-ray diffraction data of compounds 1b and 2.
Author Contributions: E.R.-V. performed the experiments; E.R.-V., I.I.P.-M. designed the experiments and
analyzed the data; E.R.-V., I.I.P.-M. and A.C. wrote the paper; E.V.G.-B. analyzed the X-ray diffraction data;
F.J.M.-M. contributed the X-ray diffraction data of
the study.
2, EA and MS; I.I.P.-M. and F.J.M.-M. conceived and conducted
Conflicts of Interest: The authors declare no conflict of interest.
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A review. Inorg. Chim. Acta 2009, 362, 4328–4339. [CrossRef]
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Sample Availability: Samples of the compounds 1a, 1b, 2–4 are available from the authors.
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