Regioselectivity of the thermal van Alphen–Hüttel rearrangement of 4- and 5-mono- and 4,5-disubstituted 3,3-diphenyl-3H-pyrazoles

Article abstract of DOI:10.1134/S1070428016060178

Thermal van Alphen–Hüttel rearrangement of methyl 3,3-diphenyl-3H-pyrazole-4-carboxylate, 3,3-diphenyl-3H-pyrazole-4-carbonitrile, and methyl 5-methyl-3,3-diphenyl-3H-pyrazole-4-carboxylate involves completely regioselective migration of one phenyl group from the 3-position to N²with formation of aromatic 1H-pyrazole system. Thermal rearrangement of methyl 3,3-diphenyl-3H-pyrazole-5-carboxylate leads to the formation of methyl 4,5-diphenyl-1H-pyrazole-3-carboxylate as a result of migration of the 3-phenyl group exclusively to the C⁴atom and subsequent prototropic isomerization. Under analogous conditions, methyl 4-methyl-3,3-diphenyl-3H-pyrazole-5-carboxylate, methyl 5-(methanesulfonyl)-3,3-diphenyl-3H-pyrazole-4-carboxylate, methyl 5-(benzenesulfonyl)-3,3-diphenyl-3H-pyrazole-4-carboxylate, and dimethyl 3,3-diphenyl-3H-pyrazole-4,5-dicarboxylate have been regioselectively converted into the corresponding 4H-pyrazoles. Thermolysis of 5-(4-methylbenzenesulfonyl)-3,3-diphenyl-3H-pyrazole-4-carbonitrile gives rise to a mixture of 1H- and 4H-pyrazoles, the former considerably prevailing, whereas the corresponding 1H-pyrazoles are formed as the only product from 5-(methanesulfonyl)- and 5-(benzenesulfonyl)-3,3-diphenyl-3H-pyrazole-4-carbonitriles.

Full text of DOI:10.1134/S1070428016060178

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 6, pp. 862–872. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © V.A. Vasin, V.V. Razin, E.V. Bezrukova, P.S. Petrov, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 6,
pp. 876–886.
Regioselectivity of the Thermal van Alphen–Hüttel
Rearrangement of 4- and 5-Mono- and 4,5-Disubstituted
3
,3-Diphenyl-3H-pyrazoles
a
b
a
a
V. A. Vasin ,* V. V. Razin , E. V. Bezrukova , and P. S. Petrov
a
Ogarev Mordovian State University, ul. Bol’shevistskaya 68, Saransk, 430005 Russia
e-mail: vasin@mrsu.ru
*
b
St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
Received February 10, 2016
Abstract—Thermal van Alphen–Hüttel rearrangement of methyl 3,3-diphenyl-3H-pyrazole-4-carboxylate,
,3-diphenyl-3H-pyrazole-4-carbonitrile, and methyl 5-methyl-3,3-diphenyl-3H-pyrazole-4-carboxylate
3
2
involves completely regioselective migration of one phenyl group from the 3-position to N with formation of
aromatic 1H-pyrazole system. Thermal rearrangement of methyl 3,3-diphenyl-3H-pyrazole-5-carboxylate leads
to the formation of methyl 4,5-diphenyl-1H-pyrazole-3-carboxylate as a result of migration of the 3-phenyl
4
group exclusively to the C atom and subsequent prototropic isomerization. Under analogous conditions,
methyl 4-methyl-3,3-diphenyl-3H-pyrazole-5-carboxylate, methyl 5-(methanesulfonyl)-3,3-diphenyl-3H-pyra-
zole-4-carboxylate, methyl 5-(benzenesulfonyl)-3,3-diphenyl-3H-pyrazole-4-carboxylate, and dimethyl
3
4
,3-diphenyl-3H-pyrazole-4,5-dicarboxylate have been regioselectively converted into the corresponding
H-pyrazoles. Thermolysis of 5-(4-methylbenzenesulfonyl)-3,3-diphenyl-3H-pyrazole-4-carbonitrile gives rise
to a mixture of 1H- and 4H-pyrazoles, the former considerably prevailing, whereas the corresponding
1
3
H-pyrazoles are formed as the only product from 5-(methanesulfonyl)- and 5-(benzenesulfonyl)-3,3-diphenyl-
H-pyrazole-4-carbonitriles.
DOI: 10.1134/S1070428016060178
It is known [1] that 3,3-disubstituted 3H-pyrazoles
undergo thermal or acid-catalyzed 1,5-sigmatropic van
Alphen–Hüttel rearrangement [2, 3] into 1H- and/or
tuted 3H-pyrazoles 1a, 1b, 2a, and 2b is completely
regioselective; the regioselectivity of the rearrange-
ment of methoxycarbonyl and cyano compounds 1c,
1d, and 2c is somewhat lower due to formation of
minor alternative isomerization products.
4
1
H-pyrazoles. Despite higher stability of the aromatic
H-pyrazole system relative to nonaromatic 4H-pyra-
zoles, the latter sometimes appear to be the major or
only isomerization product [4]. Factors responsible
for regioselectivity of this rearrangement remain so far
the matter of discussion.
We have also noticed that the thermolysis of two
,3-diphenyl-3H-pyrazoles 3e [9] and 3f [10] contain-
ing an electron-withdrawing substituent in the 5-posi-
tion and free 4-position is completely regioselective
and is directed toward the corresponding 4H-pyrazole
which undergoes fast prototropic isomerization into
3
While trying to shed light on this problem, we com-
pared the known results of thermal van Alphen–Hüttel
rearrangement of three pairs of 4,5-disubstituted
W
R
R
W
3
,3-diphenyl-3H-pyrazoles 1a–1c and 2a–2c differing
by the nature of one electron-withdrawing substituent
and its position, as well as of structurally related com-
pound 1d [5–8]. Pyrazoles 1a–1d with the electron-
Ph
Ph
1a–1d, 4c, 4d, 5c
N
Ph
Ph
2a–2c, 3c, 3e–3j, 6c
b, 7c, 7k, 8a, 8b, 8k
N
N
N
4
withdrawing substituent on C are mainly converted
7
into N-phenyl-1H-pyrazole derivatives, whereas regio-
isomeric 5-W-substituted (W is an electron-withdraw-
ing group) compounds 2a–2c give rise preferentially to
1
8
, 2, R = Ph; 3, 4, R = H; 5, 6, R = Me; 7, R = COOMe;
, R = CN; hereinafter, W = Ts (a), SO Me (b), COOMe (c),
(f), Me (g), Ph (h), cycloalk-1-en-
1-yl (i), H (j), SO Ph (k).
2
CN (d), Ac (e), P(O)Ph
2
4
H-pyrazoles. The isomerization of sulfonyl-substi-
2
8
62

REGIOSELECTIVITY OF THE THERMAL VAN ALPHEN–HÜTTEL REARRANGEMENT
863
Scheme 1.
R
SO Me
2
Ph C=N , Et O
MnO2
2
2
2
R
7
b, 8b
SO Me
2
Ph
Ph
N
N
H
9
, 10
11, 12
9
, 11, R = COOMe; 10, 12, R = CN.
Scheme 2.
W
R
W
R
Ph
Ph
4
c, 4d, 5c
N
N
Ph
N
N
Ph
13c, 13d, 20c
1
4c, 14d, 21c
R
R
COOMe
COOMe
COOMe
COOMe
Ph
Ph
Ph
Ph
3
c, 6c
N
N
R = H
NH
N
Ph
Ph
Ph
N
N
N
N
H
Ph
1
7c, 19c
16c, 18c
15
15'
1
3, 14, 16, 17, R = H; 18–21, R = Me.
1
H-pyrazole derivative. On the other hand, analogous
regioselectivity is observed in the isomerization of
,3-diphenyl-3H-pyrazoles 3g [11], 3h [12, 13], and 3i
[18]. 3H-Pyrazoles 7b and 8b were not reported
previously; they were synthesized in this work in two
steps starting from methyl 3-(methanesulfonyl)prop-
2-enoate (9) and 3-(methanesulfonyl)prop-2-enenitrile
(10), respectively, through 4,5-dihydro-1H-pyrazoles
11 and 12 (Scheme 1, see [16]). The structure of 7b,
3
5
[14] with a hydrocarbon substituent on C and free
4
3
-position. Finally, it is known [15] that 3,3-diphenyl-
H-pyrazole (3j) having no substituents in positions 4
1
13
and 5 rearranges into 1H-pyrazole through interme-
diate 4H-pyrazole. We have found no published data
on 4-substituted 3,3-diphenyl-3H-pyrazoles with no
8b, 11, and 12 was confirmed by IR and H and
C
NMR spectra with account taken of spectral param-
eters of model arenesulfonyl-substituted analogs [16].
5
substituent on C and their thermal transformations.
Initially, we studied thermal transformations of 3H-
pyrazoles 3c, 4c, and 4d. When pyrazoles 4c and 4d
The present study was aimed at elucidating the
effect of the nature of substituents and their position in
4
with an acceptor substituent on C were heated in
3
1
,3-diphenyl-3H-pyrazoles on the direction of thermal
,5-sigmatropic shift of the phenyl group from C . For
boiling toluene for 1 h, completely regioselective
3
3
1,5-sigmatropic shift of one phenyl group from C to
2
this purpose, the substrate series was considerably
extended by including three 4- and 5-monosubstituted
3
ative 3c and 4-methoxycarbonyl and 4-cyano deriv-
atives 4c and 4d, as well as eight 4,5-disubstituted
3
compounds 5c and 6c with one electron-withdrawing
substituent and pyrazoles 7b, 7c, 7k, 8a, 8b, and 8k
possessing two electron-withdrawing substituents.
N was observed with formation of known N-phenyl-
1H-pyrazoles 13c [19] and 13d [20, 21] (Scheme 2).
Thermolysis of 5-(methoxycarbonyl) derivative 3c
under analogous conditions was reported to produce
1H-pyrazole 15 [18]. We have reproduced this experi-
ment and reliably characterized compound 15 by
,3-diphenyl-3H-pyrazoles: 5-methoxycarbonyl deriv-
,3-diphenyl-3H-pyrazoles, namely two regioisomeric
1
spectral data. Obviously, this result should be treated
4
as tandem 1,5-phenyl shift to C and proton transfer to
1
Pyrazole 15 in solution exists in equilibrium with tautomer 15′
Initial 3H-pyrazoles 3s, 4c, 4d, 7k, 8a, and 8k were
1
3
(
Scheme 2), which is reflected in the C NMR spectrum by
synthesized according to the procedures reported in
broadening of signals from carbon atoms of the five-membered
heterocycle and averaging of signals from carbon atoms of the
two nonequivalent benzene rings.
[16], compounds 5c and 6c were prepared as described
in [17], and pyrazole 7c was synthesized according to
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

8
64
VASIN et al.
Scheme 3.
Ph
COOMe
COOMe
MeOC(O)
COOMe
Ph
COOMe
Ph
Ph
+
7c
+
COOMe
N
N
N
Ph
Ph
COOMe
N
N
N
COOMe
Ph
2
5
23
22
24
the nitrogen atom. The second step of this process is
very fast, and intermediate 4H-pyrazole 16c could not
be detected.
diester 25 that could result from migration of phenyl
group to N was detected. While reproducing the
2
results of [18, 24, 25] on acid-catalyzed isomerization
of 7c we also isolated 4H-pyrazole 22 as the only prod-
uct which remained unchanged after prolonged (8 h)
heating in glacial acetic acid. The UV spectrum of 22
provided an additional support of its structure (cf. the
data for its analog 18c [17]). Almost identical UV spec-
trum (λmax 314 nm, logε 4.13) was erroneously con-
sidered in [25] as an evidence for the structure of 23.
Undoubtedly, it was interesting to compare the
directions of isomerization of regioisomeric 3H-pyra-
zoles 5c and 6c (homologs of the 3c/4c pair and
analogs of the 1c/2c pair). The transformation of 6c
into 4H-pyrazole 18c as a result of 1,5-phenyl shift
4
toward C was described in [17]. We also obtained
compound 18c under the conditions reported in [17],
and its spectral parameters coincided with those given
in [7]. The thermal rearrangement of 5c (benzene,
microwave reactor, 140°C, 40 min) afforded known
Compounds 22 and 24 were isolated as crystalline
substances by silica gel column chromatography. The
1
13
structure of 22 follows from its H and C NMR
2
3
5
N-phenyl-3H-pyrazole 20c [22] as the only product.
spectra. In particular, signals of C and C deshielded
by the effect of nitrogen atoms appeared in the
Our results indicated similarity in the behavior of
regioisomeric couples 5c/6c and 3c/4c in the van
Alphen–Hüttel rearrangement, but the transformations
of 1c and 2c were less selective, indicating somewhat
different effects of methyl and phenyl groups on the
isomerization direction.
1
3
C NMR spectrum at δ 168.0 and 175.4 ppm, which
C
is typical of such compounds [1, 5, 7, 17]. We believe
that indene 24 is formed from 3H-pyrazole 7c via
denitrogenation through intermediate cyclopropene
(
cf. [5]), which is concurrent to the van Alphen–Hüttel
We then turned to the thermal isomerization of
rearrangement.
3
H-pyrazole 7c having two similar electron-withdraw-
In the next step of our study we examined thermal
van Alphen–Hüttel rearrangement of 4,5-disubstituted
4
ing substituents (methoxycarbonyl groups) on C and
C . The transformation of 7c into 22 was described by
5
3
H-pyrazoles 7b, 8a, 8b, and 8k containing different
Baumes et al. [24], and the structure of 22 was
determined by chemical methods. Simultaneously, the
authors [24] corrected the results of [18, 25], where the
thermolysis product of 7c was assigned the structure of
N-(methoxycarbonyl)-1H-pyrazole 23. In these studies
4
5
electron-withdrawing groups on C and C . Compound
k was completely converted into 4H-pyrazole 26k on
7
heating in boiling benzene for 10 min [16]. Analogous
isomerization of 7b into 26b in boiling benzene was
complete in 40–80 min. 3H-Pyrazole 8a gave rise to
a mixture of 4H- and 1H-pyrazoles 27a and 28a at
[
18, 24, 25], the isomerization was carried out by
heating in acetic acid, which did not ruled out acid
catalysis. Therefore, we tried to accomplish purely
thermal isomerization of 3H-pyrazole 7c. By heating
compound 7c in boiling ethanol for 40 min we also
obtained 4H-pyrazole 22 with a small impurity (5–8%)
of known indene 24 [26, 27] (Scheme 3). The same
a ratio of 1:3 on heating in CCl for 1 h. The rear-
4
rangement of 3H-pyrazoles 8b and 8k was more
selective, and 1H-pyrazoles 28b and 28k were the only
products (Scheme 4).
Scheme 4.
4
H-pyrazole 22 was formed in a mixture with 24 at
1
R
R
W
W
a ratio of 1:1.3 (according to the H NMR data) when
compound 7c was refluxed in toluene for 1 h. No
Ph
Ph
∆
7b, 7k, 8a, 8b, 8k
+
N
Ph
N
N
2
N
Analogous result (i.e., exclusive formation of N-phenyl-1H-pyr-
azole derivative) was obtained in [23] in the thermolysis of ethyl
Ph
3
,3-diphenyl-3H-pyrazole-5-carboxylate (analog of 5c).
26b, 26k, 27a
28a, 28b,28k
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

REGIOSELECTIVITY OF THE THERMAL VAN ALPHEN–HÜTTEL REARRANGEMENT
865
Scheme 5.
R
W
R
W
To N2
To C4
2
7
a–2c, 3c, 3e–3j, 6c
b, 7c, 7k, 8a, 8b, 8k
Ph
Ph
Ph
N
N
N
N
Ph
TS1
TS2
W
R
W
R
To N2
To C4
Ph
Ph
1
a–1d, 4c, 4d, 5c
Ph
N
N
N
N
Ph
TS3
TS4
4
H-Pyrazoles 26b and 26k and 1H-pyrazoles 28a,
8b, and 28k were isolated in the crystalline state and
characterized by spectral data. Compounds 28a, 28b,
in positions 4 and 5, as well as to the position of
nitrogen atoms.
2
Let us consider first those 3H-pyrazoles whose
isomerization leads to 4H-pyrazoles, in particular
1
3
3
and 28k showed in the C NMR spectra C and
C signals typical of 1H-pyrazoles at δ ~146 and
52 ppm, which is consistent with published data for
structurally related compounds [5, 7]. We failed to
isolate 4H-pyrazole 27a which was detected in the
reaction mixture by C NMR (δ
field signals of C and C , see above).
5
C
4
,5-unsubstituted compound 3j and 5-monosubstituted
1
derivatives 3c, and 3e–3i. Transition state TS2 for
pyrazoles 3j and 3g is more stable than TS2 due to the
presence of two electronegative nitrogen atoms in the
negatively charged moiety. Transition state TS1 con-
tains only one nitrogen atom in the negatively charged
moiety, whereas the second nitrogen atom resides in
the positively charged moiety, so that TS1 is destabil-
ized. 4,5-Disubstituted 3H-pyrazoles 2a, 2b, and 6c
1
3
4
C
~80 ppm and down-
3
5
Thus, the major pathway of the thermolysis of
H-pyrazoles 2a–2c, 3c, 3e–3j, 6c, 7b, 7c, and 7k is
,5-phenyl shift to C , whereas 3-phenyl group in
H-pyrazoles 1a–1d, 4c, 4d, 5c, 8a, 8b, and 8k
preferentially migrates to N . We previously [5, 7]
proposed a qualitative interpretation of the regioselec-
tivity in the isomerization of 3,3-diphenyl-3H-pyra-
zoles 1a–1d and 2a–2c, according to which transition
states for each of the two possible isomerization path-
ways is postulated to be equivalent to the π-system of
the corresponding nonalternant diazabicyclo[3.1.0]-
3
1
3
4
5
with one electron-withdrawing substituent on C show
2
analogous complete regioselectivity, which is not sur-
prising since TS2 is additionally stabilized by in-
creased electronegativity of the terminal allylic carbon
atom bearing an electron-withdrawing substituent.
Somewhat unexpectedly, pyrazole 2c displayed lower
regioselectivity.
Consider next transition states for the rearrange-
3
hexatriene. Let us consider to which extent this
ment of pyrazoles 7b, 7c, 7k, 8a, 8b, and 8k pos-
4
approach is applicable for the prediction of the isomer-
ization direction of 3H-pyrazoles listed above. The
transition states for both isomerization pathways are
denoted as TS1–TS4 (Scheme 5). All these transition
states are dipolar ions, and charge distribution therein
is estimated by the Hückel molecular orbital (HMO)
method for the bicyclo[3.1.0]hexatriene π-system [29]:
the negative charge is delocalized over the allylic
fragment where the terminal atoms possess the main
charge, and the middle atom bears a minor negative
charge; the positive charge is delocalized over the
three-membered ring. Obviously, such dipolar ion
should be sensitive to electronic effects of substituents
sessing two electron-withdrawing substituents on C
5
and C . It was difficult to determine whether TS1 or
TS2 is preferred for pyrazole 7c. In this case, two
structural factors act in the opposite directions: favor-
able arrangement of the nitrogen atoms stabilizes TS2,
whereas two identical electron-withdrawing methoxy-
carbonyl groups stabilize TS1 to a greater extent. The
different regioselectivities of the isomerization of 7b,
7
k, 8a, 8b, and 8k are determined by the different
strengths of the electron-withdrawing substituent W on
4
C . The rearrangement of 7b and 7k through TS2 is
preferred due to stabilizing effect of the strong elec-
tron-withdrawing sulfonyl group (W), which com-
pensates for destabilizing effect of relatively weak
electron-withdrawing methoxycarbonyl group (R). In
the case of pyrazoles 8a, 8b, and 8k, TS1 becomes
3
Analogous approach based on the Dewar molecular orbital per-
turbation theory of pericyclic reactions [28] was proposed in [29]
to interpret 1,5-hydride shift in cyclopentadiene.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

8
66
VASIN et al.
preferable since strong electron-withdrawing cyano
The proposed qualitative HMO interpretation of the
experimentally observed differences in the regioselec-
tivity of thermal van Alphen–Hüttel rearrangement of
3H-pyrazoles in relation to the position and nature of
substituents therein is quite consistent with the results
of DFT/PBE calculations (PRIRODA 06) of the activa-
tion barriers for the two isomerization pathways of
3H-pyrazoles 1c–7c, 3d, 3j, and 4d, leading to
4H-pyrazoles and N-phenyl-1H-pyrazoles, and of the
relative energies of the transformation products (see
table). In all cases, the 1,5-phenyl shift products were
more stable than the initial 3H-pyrazoles, but to con-
siderably different extents. 4H-Pyrazoles were more
stable by 5–13 kcal/mol, and N-phenyl-1H-pyrazoles,
by 32–35 kcal/mol. This difference seems to be quite
reasonable taking into account aromaticity of the
group (R) simultaneously destabilizes TS2 {cf.
–
Hammett constants σ and σ : 1.13 and 0.59 (CO Me),
I
2
1
.00 and 0.57 (CN), 0.74 and 0.32 (COOMe) [30]}.
Analogous result (i.e., the formation of the correspond-
ing N-phenyl-1H-pyrazole) was obtained previously
[10] in the thermolysis of 4,5-bis(diphenylphosphoryl)-
3
,3-diphenyl-3H-pyrazole containing a stronger (than
methoxycarbonyl) electron-withdrawing substituent on
4
C , which is structurally related to 7c.
3
H-Pyrazoles 1a–1d, 4c, 4d, and 5c possessing one
electron-withdrawing substituent in the 4-position are
converted mainly into N-phenyl-1H-pyrazoles. The
relative stability of the corresponding transition states
TS3 and TS4 cannot be estimated because of opposite
effects of two structural factors: position of nitrogen
atoms and electron-withdrawing effect of the 4-sub-
stituent. Nevertheless, it is possible to correlate the
stability of transition states with the experimental data
assuming better stabilization of TS3 by the substituent
W and destabilization of TS4 by the same substituent.
1
H-pyrazole system. It may be concluded that the
isomerization of 3H-pyrazoles into less stable 4H-pyr-
azole should be kinetically controlled, i.e., the activa-
tion barrier to this transformation showed be lower
than the barrier to the isomerization into 1H-pyrazole.
In fact, the calculated activation barrier to the
rearrangement of 3,3-diphenyl-3H-pyrazole 3j into
H-pyrazole is lower by only 0.6 kcal/mol than that to
The lower regioselectivity of the rearrangement of
c and 1d may be attributed to the relatively weak
electron-withdrawing effect of the substituent W in
1
4
the transformation into N-phenyl-1H-pyrazole. This
result indicates quite small contribution of the effect of
the position of nitrogen atoms (see above). The barrier
to the transformation of 3H-pyrazole 4c into aromatic
N-phenyl-1H-pyrazole 13c is lower by 4.8 kcal/mol
than that to the transformation into 4H-pyrazole 14c.
On the other hand, the barrier to the isomerization of
combination with stabilization of TS4 by the phenyl
substituent capable of acting as a weak acceptor (σ =
–
0
.02, σ = 0.12 [30]).
I
Calculated (DFT/PBE) activation barriers to the transforma-
tion of 3H-pyrazoles into 1H- and 4H-pyrazoles and relative
a
energies of the transformation products
3
c into thermodynamically less stable 4H-pyrazole 16c
b
Activation barrier,
kcal/mol
Relative energy,
kcal/mol
is lower by 4.1 kcal/mol than the barrier to the trans-
formation into N-phenyl-1H-pyrazole 17c (Fig. 1).
3
H-Pyra-
zole no.
to 4H-pyr- to 1H-pyr- 4H-pyr-
1H-pyr-
azole
Largely similar situation is observed in the rear-
azole
25.6
23.8
19.5
19.3
22.0
26.0
25.3
25.9
23.8
21.7
azole
22.4
24.1
23.6
23.2
22.9
21.2
22.9
21.3
25.0
22.3
azole
–10.3
0–4.4
–13.0
–13.6
–13.8
0–8.3
0–5.4
0–8.8
0–6.5
–11.4
4
rangements of 3H-pyrazoles 3d, and 4d. Here, the
energy differences between the transition states are
2
4
1
2
3
3
3
4
4
5
6
7
c
c
c
d
j
–32.4
–33.3
–34.8
–34.6
–33.5
–35.0
–35.0
–33.5
–31.9
–35.4
.6 kcal/mol in favor of N-phenyl-1H-pyrazole 13d for
d and 3.9 kcal/mol in favor of 4H-pyrazole 16d for
3d. The activation barrier to the transformation of
,5-disubstituted 3H-pyrazole 5c into N-phenyl-1H-
4
pyrazole 20c is lower by 4.6 kcal/mol than that found
for the alternative pathway, i.e., the situation is ap-
proximately similar to that observed for 4c. The barrier
to the transformation of 6c into 19c is lower by only
c
d
c
c
c
1
.2 kcal/mol than into N-phenyl-1H-pyrazole 18c. This
difference is considerably smaller than that in the rear-
a
The total energies of all compounds and transition states were
calculated with correction for zero-point vibration energy (ZPE).
In all cases, the relative energies were calculated with respect to
rangement of monosubstituted analog 3c, though (in
b
4
There are no published data on the synthesis and thermal isomer-
the corresponding 3H-pyrazole.
ization of 3H-pyrazole 3d.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

REGIOSELECTIVITY OF THE THERMAL VAN ALPHEN–HÜTTEL REARRANGEMENT
867
ΔE, kcal/mol
terms of the qualitative model) the 4-methyl group in
2
6.0
6
c should provide additional stabilization of the transi-
2
3.6
2
1.2
tion state leading to 4H-pyrazole, as compared to 3c.
As concerns pyrazole 7c, its isomerization into 22
2
0
19.5
(
Fig. 2) is more favorable by only 0.6 kcal/mol.
The results of calculations for 3H-pyrazoles 1c and
c are noticeable. These compounds showed the op-
10
0
2
posite but incomplete regioselectivity of the van
Alphen–Hüttel rearrangement. The calculated barriers
for the transformation of 2c were in a good agreement
with the experimental data. The rearrangement of 2c
into 4H-pyrazole is more favorable than the isomeriza-
tion into 1H-pyrazole by only 0.3 kcal/mol. However,
the calculations performed for 3H-pyrazole 1c predict
preferential formation of 1H-pyrazole (the correspond-
ing activation barrier is lower by 3.2 kcal/mol). This
is less consistent with the experimental data [6, 7, 31],
according to which the fraction of 4H-pyrazole deriva-
tive is appreciable. Presumably, the formation of
0
.0
0.0
3c
4
c
–
8.3
4c
1
–13.0
–
–
–
10
20
30
1
6c
–34.8
–
35.0
3c
17c
1
4
H-pyrazole from 1c is determined by the contribution
Fig. 1. Calculated (DFT/PBE) energy profiles for the trans-
formations of 3H-pyrazoles 3c and 4c into 1H- and 4H-pyr-
azoles 13c, 14c, 16c, and 17c.
of the acid-catalyzed isomerization leading exclusively
to 4H-pyrazole rather than by lower regioselectivity
5
of the thermal isomerization of 1c. We performed
thermolysis of 1c under the conditions described in [7]
but with addition of triethylamine in order to eliminate
possible traces of mineral acid from the reaction
mixture or reactor surface. However, the product ratio
did not change and was ~4:1 in favor of 1H-pyrazole.
Therefore, the reason for the observed inconsistency
between the calculated and experimental data remains
unclear.
ΔE, kcal/mol
25.9
2
5.0
2
3.8
22.3
2
1.7
2
1.3
2
1
0
0
0
0
.0
0.0
0.0
5c
7c
6
c
–6.5
–
8.8
1c
–
11.4
–
–
–
10
20
30
19c
2
2
2
Thus, though quantum chemical calculations were
performed only for some selected 3,3-diphenyl-3H-
pyrazoles, their results in combination with qualitative
HMO analysis of the transition states generally make it
possible to predict regioselectivity of the thermal van
Alphen–Hüttel 1,5-sigmatropic rearrangement of these
compounds with a high probability. The regioselec-
tivity of this rearrangement is largely determined by
the ability of substituents in positions 4 and 5 of
–31.9
–
33.5
0c
–
35.4
1
8c
2
24
Fig. 2. Calculated (DFT/PBE) energy profiles for the trans-
formations of 3H-pyrazoles 5c–7c into compounds 18c–21c,
2
2, and 24.
3
,3-diphenyl-3H-pyrazoles to stabilize the correspond-
recorded in KBr on an InfraLYuM FT-02 spectrometer
with Fourier transform. The UV spectra were meas-
ured on a Shimadzu UV-2600 spectrophotometer and
were processed using UV Probe 2.4. The elemental
analyses were obtained on a VarioMICRO CHNS
analyzer. Analytical TLC was performed on Sorbfil
plates with light petroleum ether–acetone (4:1) as
eluent; the chromatograms were developed in a iodine
chamber. The melting points were determined in glass
capillaries on a Mettler Toledo MP-50 melting point
analyzer.
ing transition states.
EXPERIMENTAL
1
13
The H and C NMR spectra were recorded from
solutions in CDCl on a JEOL ECX-400 spectrometer
at 400 and 100 MHz, respectively. The IR spectra were
3
5
When 3H-pyrazole 1c was kept in glacial acetic acid in the pres-
2 4
ence of a catalytic amount of H SO at 20°C, the corresponding
4
H-pyrazole was formed with complete regioselectivity [7].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

8
68
VASIN et al.
Quantum chemical calculations of pyrazole and
C H N O S. Calculated, %: C 60.66; H 4.53;
1
8
16
2
4
transition state structures were carried out in several
steps. First, initial sets of 1H-, 3H-, and 4H-pyrazole
conformers were simulated by the MMFF94 method
N 7.86; S 9.00.
5
-(Methanesulfonyl)-3,3-diphenyl-3H-pyrazole-
4
-carbonitrile (8b). Yield 71%, yellow crystals,
–
1
[32] using Marvin Beans 15.5.4 [33]. The structures of
mp 96–97°C (from Et O). IR spectrum, ν, cm :
2
most favorable conformers were optimized at the RM1
level of theory [34] using MOPAC2012 [35]. The final
structures were obtained in terms of the DFT/PBE
approximation (PRIRODA 06 software [36], L1 basis
set [37]). Transition states were localized by scanning
the potential energy surface along the selected reaction
coordinate and calculating the corresponding Hessian
eigenvalues (one imaginary frequency); the transition
states were verified by the intrinsic reaction coordinate
2
924 w, 2215 w, 1493 m, 1451 m, 1408 w, 1339 v.s,
1150 v.s, 953 m, 775 s, 752 s, 694 s, 660 m, 640 w,
1
5
40 s, 517 m, 494 m. H NMR spectrum, δ, ppm: 3.48
s (3H, Me), 7.29–7.32 m (4H, Harom), 7.40–7.46 m
13
(
6H, H ). C NMR spectrum, δ , ppm: 42.5 (Me),
arom C
3
110.1 (C ), 112.0 (CN), 127.8 (4C, C ), 129.8 (4C,
arom
4
Carom), 130.4 (2C, Carom), 132.4 (2C, Carom), 133.2 (C ),
1
S 9.87. C H N O S. Calculated, %: C 63.14; H 4.05;
N 12.99; S 9.91.
5
57.8 (C ). Found, %: C 63.18; H 4.11; N 12.84;
1
7
13
3
2
(
IRC) procedure in two directions.
3
H-Pyrazoles 3c, 4c, 4d, 8a, and 8k were synthe-
Dimethyl 3,3-diphenyl-3H-pyrazole-4,5-dicar-
boxylate (7c). A solution of 1 g (5.6 mmol) of
diphenyldiazomethane in 10 mL of anhydrous diethyl
ether was added to a solution of 0.73 g (5.1 mmol) of
dimethyl acetylenedicarboxylate in 40 mL of anhy-
drous diethyl ether. The mixture was left to stand in
a partially open flask, and yellow crystals separated as
the solvent gradually evaporated. The crystals were
filtered off. Yield 1.12 g (65%), mp 93–94°C (from
sized according to the procedures described in [16];
diphenyldiazomethane was prepared as described in
38]. Commercial dimethyl acetylenedicarboxylate and
[
methanesulfonyl chloride (from Aldrich) were used.
Methyl 5-methyl-3,3-diphenyl-3H-pyrazole-4-
carboxylate (5c) was synthesized as described in [17].
H NMR spectrum, δ, ppm: 2.82 s (3H, Me), 3.73 s
3H, OMe), 7.16–7.20 m (4H, Harom), 7.28–7.34 m
6H, Harom). C NMR spectrum, δ , ppm: 14.4 (Me),
1
(
(
5
(
(
–
1
13
Et O) [18]. IR spectrum, ν, cm : 1748 s, 1725 v.s,
2
C
3
1651 w, 1497 w, 1435 m, 1339 m, 1316 m, 1277 m,
2.2 (OMe), 108.5 (C ), 128.45 (4C, Carom), 128.53
1
1
242 m, 1204 m, 1142 m. H NMR spectrum, δ, ppm:
2C, C ), 128.7 (4C, Carom), 135.1 (2C, Carom), 139.7
arom
4
5
3.77 s (3H, OMe), 4.02 s (3H, OMe), 7.20–7.24 m
C ), 160.6 (C ), 163.2 (C=O).
1
3
(
4H, Harom), 7.30–7.40 m (6H, Harom). C NMR spec-
3
Oxidative dehydrogenation of dihydropyrazoles
1 and 12 (general procedure). Activated manga-
trum, δ , ppm: 53.3 (2C, OMe), 110.5 (C ), 128.4
C
1
(
1
1
4C, Carom), 129.0 w (4C, C ), 129.3 (2C, Carom),
33.7 (2C, Carom), 146.6 (C ), 152.9 (C ), 160.5 (C=O),
63.4 (C=O).
arom
4
5
nese(IV) oxide [39], 2.6 g (30 mmol), was added to
a solution of 1.5 mmol of compound 11 or 12 in 40 mL
of a 1:3 mixture of anhydrous benzene and methylene
chloride under continuous stirring in an argon atmo-
sphere. The mixture was stirred for 48 h, filtered
through a 1-cm layer of silica gel, and evaporated
under reduced pressure on a rotary evaporator, and the
residue was washed with light petroleum ether.
Iodosulfonation–dehydroiodination of acrylic
acid derivatives (general procedure). An aqueous
solution of sodium methanesulfinate was obtained by
reduction of 17 g (150 mmol) of methanesulfonyl
chloride with 20.8 g (165 mmol) of Na SO in the
2
3
presence of 25.2 g (300 mmol) of NaHCO [40]. The
3
Methyl 5-(methanesulfonyl)-3,3-diphenyl-3H-
pyrazole-4-carboxylate (7b). Yield 90%, light yellow
crystals, mp 103–104°C. IR spectrum, ν, cm : 1736 s,
solution was treated with 13 g (51 mmol) of iodine in
80 ml of benzene under stirring over a period of
40 min. The benzene layer was separated, dried over
–
1
1
1
7
617 w, 1600 w, 1582 w, 1489 m, 1447 m, 1431 m,
331 v.s, 1289 s, 1157 s, 1130 s, 957 m, 791 s, 760 m,
49 m, 702 m, 529 m, 498 m. H NMR spectrum, δ,
MgSO , and added to a solution of 40 mmol of methyl
4
acrylate or acrylonitrile in 20 mL of benzene, and the
mixture was placed into a Pyrex flask and irradiated
for 1 h with a halogen filament lamp (500 W). The sol-
vent was removed under reduced pressure on a rotary
evaporator, the residue was treated with 100 mL of
anhydrous methylene chloride, and 3 g (30 mmol) of
triethylamine was added dropwise under stirring. The
mixture was stirred for 2 h, the precipitate of triethyl-
1
ppm: 3.42 s (3H, Me), 3.81 s (3H, OMe), 7.20–7.24 m
13
(
4H, Harom), 7.34–7.43 m (6H, Harom). C NMR spec-
3
trum, δ , ppm: 43.1 (Me), 53.8 (OMe), 111.8 (C ),
1
1
C
28.4 (4C, Carom), 129.2 (4C, C ), 129.7 (2C, Carom),
arom
4
5
32.8 (2C, Carom), 152.6 (C ), 153.3 (C ), 161.9
(
C=O). Found, %: C 60.62; H 4.49; N 7.83; S 8.96.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

REGIOSELECTIVITY OF THE THERMAL VAN ALPHEN–HÜTTEL REARRANGEMENT
869
amine hydroiodide was filtered off and washed on
a filter with 15 mL of ethanol–petroleum ether (1:2),
the filtrate was combined with the washings and evap-
orated, and the residue was recrystallized.
3-(Methanesulfonyl)-5,5-diphenyl-4,5-dihydro-
1H-pyrazole-4-carbonitrile (12). Yield 68%, color-
–
1
less crystals, mp 71–72°C. IR spectrum, ν, cm :
2978 m, 2928 w, 2836 w, 2242 w, 1536 m, 1497 m,
1
451 m, 1431 m, 1389 w, 1370 m, 1319 v.s, 1238 w,
Methyl (2E)-3-(methanesulfonyl)prop-2-enoate
1196 m, 1146 s, 1103 m, 1069 m, 1019 w, 1003 w,
(
9). Yield 2.3 g (74%), mp 77–78°C. IR spectrum, ν,
1
–
1
961 m, 772 s, 702 s, 529 s, 502 m. H NMR spectrum,
δ, ppm: 3.20 s (3H, Me), 5.07 s (1H, 4-H), 7.29 br.s
cm : 1717 s, 1640 w, 1458 w, 1439 m, 1416 m,
1
9
5
3
335 s, 1312 v.s, 1296 v.s, 1242 s, 1173 m, 1138 v.s,
99 m, 980 s, 922 m, 868 w, 799 m, 775 m, 698 w,
(
1H, NH), 7.22–7.25 m (2H, Harom), 7.30–7.32 m (2H,
1
3
1
Harom), 7.39–7.42 m (6H, H ). C NMR spectrum,
arom
4
21 m, 509 s, 467 m. H NMR spectrum, δ, ppm:
5
δ , ppm: 43.1 (Me), 49.5 (C ), 81.6 (C ), 113.4 (CN),
C
.01 s (3H, Me), 3.82 s (3H, OMe), 6.84 d (1H, 2-H,
1
3
125.9 (2C, Carom), 127.5 (2C, Carom), 129.1 (2C, Carom),
1
141.1 w (Carom), 141.9 (C ). Found, %: C 62.78;
H 4.51; N 12.83; S 9.86. C H N O S. Calculated, %:
C 62.75; H 4.65; N 12.91; S 9.85.
J = 15.2 Hz), 7.93 d (1H, 3-H, J = 15.2 Hz). C NMR
29.4 (Carom), 129.5 (2C, Carom), 138.6 w (Carom),
spectrum, δ , ppm: 42.4 (Me), 53.0 (OMe), 132.5
C
3
2
3
(
C ), 142.2 (C ), 163.8 (C=O). Found, %: C 36.51;
1
7
15
3
2
H 4.90; S 19.46. C H O S. Calculated, %: C 36.58;
5
8
4
H 4.91; S 19.53.
2E)-3-(Methanesulfonyl)prop-2-enenitrile (10).
Yield 1.8 g (64%), mp 103–104°C [41]. IR spectrum,
Thermal isomerization of 3H-pyrazoles 3c, 4c,
and 4d (general procedure). A solution of 0.45 mmol
of pyrazole 3c, 4c, or 4d in 3 mL of anhydrous toluene
was refluxed for 1 h under argon. The solvent was
removed on a rotary evaporator, and the residue was
analyzed by NMR. The products were N-phenyl-1H-
pyrazoles 13c and 13d and 1H-pyrazole 15c, respec-
tively.
(
–
1
ν, cm : 3071 m, 3009 m, 2928 m, 2238 m, 1617 m,
1
9
4
6
1
412 m, 1327 v.s, 1312 v.s, 1269 s, 1211 s, 1138 v.s,
72 s, 941 s, 829 s, 795 m, 752 s, 544 v.s, 521 s, 490 s,
1
55 m. H NMR spectrum, δ, ppm: 3.05 s (3H, Me),
.56 d (1H, 2-H, J = 15.8 Hz), 7.34 d (1H, 3-H, J =
1
3
5.8 Hz). C NMR spectrum, δ , ppm: 42.4 (Me),
C
2
3
1
13.1 (C ), 113.3 (CN), 147.8 (C ).
Methyl 1,5-diphenyl-1H-pyrazole-4-carboxylate
(
[
1
1
13c). Yield 65%, colorless crystals, mp 125–126°C
19]. IR spectrum, ν, cm : 2948 w, 1725 v.s (C=O),
551 m, 1497 m, 1451 m, 1389 m, 1289 m, 1223 v.s,
130 s, 1084 m, 1019 m, 772 m, 702 m, 695 m.
Reaction of compounds 9 and 10 with diphenyl-
diazomethane (general procedure). A solution of
–
1
0
.65 g (3.3 mmol) of diphenyldiazomethane in 10 mL
of anhydrous diethyl ether was added to a solution of
mmol of compound 9 or 10 in 70 mL of the same
solvent, and the mixture was kept for 24 h at 20°C in
the dark. The crystals were filtered off and washed
with diethyl ether.
1
H NMR spectrum, δ, ppm: 3.74 s (3H, OCH ), 7.17–
3
3
7
(
1
(
(
.23 m (2H, Harom), 7.24–7.38 m (8H, Harom), 8.17 s
1
3
1H, 5-H). C NMR spectrum, δ , ppm: 51.2 (OCH ),
C 3
4
13.5 (C ), 125.3 (2C, Carom), 127.9 (Carom), 128.0
2C, Carom), 128.8 (3C, Carom), 129.1 (C ), 130.5
arom
Methyl 3-(methanesulfonyl)-5,5-diphenyl-4,5-di-
hydro-1H-pyrazole-4-carboxylate (11). Yield 71%,
light yellow crystals, mp 179–180°C. IR spectrum, ν,
5
3
2C, Carom), 139.3 w (Carom), 142.4 (C ), 145.5 (C ),
1
63.3 (C=O).
–
1
1,5-Diphenyl-1H-pyrazole-4-carbonitrile (13d).
cm : 3333 s, 1748 s, 1732 s, 1543 m, 1447 m, 1431 m,
420 m, 1296 v.s, 1235 m, 1181 m, 1161 m, 1134 s,
115 m, 1088 w, 1026 m, 972 m, 957 m, 872 m, 772 s,
52 m, 706 m, 695 s, 613 m, 548 m, 525 s, 505 m.
Yield 92%, colorless crystals, mp 95–96°C; published
data: mp 102–104°C [20], 100°C [21]. IR spectrum, ν,
cm : 3067 w, 2230 s (CN), 1593 m, 1543 m, 1501 v.s,
1447 s, 1401 s, 1069 m, 965 m, 857 m, 772 s, 706 v.s,
1
1
–
1
7
1
H NMR spectrum, δ, ppm: 3.18 s (3H, Me), 3.20 s
1
6
95 s, 656 m. H NMR spectrum, δ, ppm: 7.25–7.27 m
(
7
3H, OMe), 5.01 s (1H, 4-H), 7.24–7.33 m (7H, Harom),
1
3
(2H, Harom), 7.31–7.34 m (2H, Harom), 7.35–7.39 m
(5H, Harom), 7.40–7.42 m (1H, Harom), 8.03 s (5-H).
.29 s (1H, NH), 7.36–7.41 m (3H, Harom). C NMR
4
spectrum, δ , ppm: 43.0 (Me), 52.5 (OMe), 58.9 (C ),
C
1
3
4
5
C NMR spectrum, δ , ppm: 93.8 (C ), 113.9 (CN),
C
8
(
(
0.7 (C ), 126.2 (2C, Carom), 128.15 (2C, Carom), 128.25
1
25.2 (2C, Carom), 126.6 w (Carom), 128.7 (Carom), 129.0
2C, Carom), 128.5 (Carom), 128.8 (Carom), 129.2
3
(2C, Carom), 129.1 (2C, Carom), 129.2 (2C, C ), 130.1
(
arom
2C, Carom), 139.1 (Carom), 143.3 (Carom), 146.6 (C ),
5
3
Carom), 138.6 w (Carom), 142.8 (C ), 147.6 (C ).
1
67.8 (C=O). Found, %: C 60.28; H 4.99; N 7.72;
S 9.06. C H N O S. Calculated, %: C 60.32; H 5.06;
Methyl 4,5-diphenyl-1H-pyrazole-3-carboxylate
1
8
18
2
4
N 7.82; S 8.95.
(15c). Yield 52%, mp 215–216°C (from MeOH);
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

8
70
VASIN et al.
4
published data [18]: mp 218°C (from MeOH). IR spec-
trum, ν, cm : 3279 m, 1732 v.s, 1458 m, 1443 m,
δ , ppm: 53.2 (OMe), 53.9 (OMe), 77.4 (C ), 127.8 w
C
–
1
(Carom), 128.5 (2C, Carom), 129.0 (2C, Carom), 129.2 (2C,
Carom), 129.3 (Carom), 129.8 w (Carom), 130.0 (2C,
1
1
404 m, 1292 w, 1254 m, 1208 s, 1165 m, 1103 m,
038 m, 1011 m, 768 m, 694 s. H NMR spectrum
1
C
arom
3
), 132.9 (Carom), 160.1 (C=O), 165.6 (C=O), 168.0
5
(
DMSO-d ), δ, ppm: 3.33 s (1H, NH), 3.69 s (3H,
(C ), 175.4 (C ).
6
OMe), 7.21–7.23 m (2H, Harom), 7.29–7.36 m (8H,
Dimethyl 3-phenyl-1H-indene-1,2-dicarboxylate
(24). Yield 0.18 g (36%), colorless crystals, mp 86–
87°C; published data: mp 92–93°C (from MeOH) [26],
1
3
Harom). C NMR spectrum (DMSO-d ), δ , ppm: 51.4
6
C
4
(
OMe), 127.1 br (C ), 127.5 (4C, Carom), 127.9 (4C,
3
5
–
1
Carom), 128.4 br and 132.3 br (C , C ).
93–94°C (from MeOH) [27]. IR spectrum, ν, cm :
3
1
1
6
3
083 w, 3025 w, 3013 w, 2955 w, 2901 w, 1744 v.s,
709 v.s, 1431 m, 1347 m, 1331 m, 1308 m, 1242 m,
204 s, 1161 s, 1146 s, 1123 m, 1096 m, 1034 w,
98 m. H NMR spectrum, δ, ppm: 3.66 s (3H, OMe),
.72 s (3H, OMe), 4.84 s (1H, 1-H), 7.24–7.26 m (1H,
Methyl 5-methyl-1,5-diphenyl-1H-pyrazole-4-
carboxylate (20c). A solution of 58 mg (0.2 mmol) of
3
H-pyrazole 5c in 3 mL of anhydrous benzene was
1
heated for 40 min at 140°C in a microwave reactor.
The solution was concentrated, and the colorless
crystals were filtered off. Yield 35 mg (60%), mp 129–
Harom), 7.32–7.48 m (7H, Harom), 7.63–7.65 m (1H,
Harom). C NMR spectrum, δ , ppm: 51.7 (OMe), 52.8
1
3
–
1
1
1
1
7
30°C [22]. IR spectrum, ν, cm : 1717 v.s, 1551 m,
505 m, 1462 m, 1435 m, 1420 m, 1385 m, 1312 m,
239 s, 1188 m, 1165 m, 1100 s, 1076 m, 768 m,
C
1
(
(
OMe), 55.9 (C ), 123.5 (Carom), 123.9 (Carom), 128.1
2C, Carom), 128.4 (Carom), 128.7 (Carom), 128.9 (Carom),
2
1
1
29.0 (2C, Carom), 129.7 (C ), 133.3 (Carom), 141.0
02 m, 691 m. H NMR spectrum, δ, ppm: 2.59 s (3H,
3
(
Carom), 144.3 (Carom), 155.5 (C ), 164.6 (C=O),
Me), 3.69 s (3H, OMe), 7.15–7.18 m (2H, Harom),
1
70.5 (C=O).
7
.23–7.27 m (5H, Harom), 7.29–7.36 m (3H, Harom).
1
3
C NMR spectrum, δ , ppm: 14.5 (Me), 51.5 (OMe),
Thermal isomerization of 3H-pyrazoles 7b, 8a,
C
4
111.7 (C ), 125.4 (2C, Carom), 127.8 (Carom), 128.1 (2C,
8b, and 8k (general procedure). A solution of
0.5 mmol of 3H-pyrazole 7b, 8a, 8b, or 8k in 10 mL of
anhydrous carbon tetrachloride was refluxed for 4–5 h
under argon. The solvent was removed on a rotary
evaporator, and the residue was analyzed by NMR.
From compound 7b we obtained 4H-pyrazole 26b
which was purified by recrystallization from ethanol,
the reaction with 8a gave a mixture of 27a and 28a at
a ratio of 1:3, pyrazole 8b was converted into 28b, and
Carom), 128.9 (2C, Carom), 129.1 (C ), 129.8 (Carom),
arom
3
5
1
1
30.5 (2C, Carom), 139.2 (C ), 146.6 (C ), 151.9 (Carom),
64.4 (C=O).
Thermal transformations of 3H-pyrazole 7c.
a. A solution of 0.25 g (0.75 mmol) of 3H-pyrazole 7c
in 15 mL of ethanol was refluxed for 40 min. The
solvent was removed on a rotary evaporator. According
to the NMR data, the product was compound 22 with
a small impurity of indene 24 (7%). Crystallization
from diethyl ether gave 0.15 g (60%) of 22.
8
k, into 28k. Pyrazoles 28a, 28b, and 28k were
isolated as crystalline substances. Compound 27a was
characterized by spectral data in a mixture with isomer
2
chromatography led to its transformation into pyra-
zolone 29.
b. A solution of 0.5 g (1.5 mmol) of 7c in 15 mL of
anhydrous toluene was refluxed for 1 h, and the
solvent was removed on a rotary evaporator. According
8a; attempted isolation of 27a by silica gel column
1
to the H NMR data, the residue was a mixture of 22
Methyl 5-(methanesulfonyl)-3,4-diphenyl-4H-
pyrazole-4-carboxylate (26b). Yield 0.23 g (77%),
mp 138–139°C (from petroleum ether). IR spectrum,
ν, cm : 1755 s, 1709 v.s, 1323 w, 1312 w, 1238 m,
1211 m, 737 m, 706 w, 694 m. H NMR spectrum, δ,
ppm: 3.01 s (3H, CH ), 3.77 s (3H, OMe), 7.37–7.42 m
(7H, Harom), 7.52 t (1H, Harom, J = 8.7 Hz), 7.96 d (2H,
Harom, J = 7.4 Hz). C NMR spectrum, δ , ppm: 43.4
(Me), 54.3 (OMe), 77.9 (C ), 127.1 w (Carom), 128.5 w
(Carom), 128.7 (2C, Carom), 129.5 (2C, Carom), 129.96
(Carom), 130.04 (2C, Carom), 133.4 (Carom), 164.4 (C=O),
175.3 (C ), 175.6 (C ). Found, %: C 60.68; H 4.47;
N 7.82; S 9.06. C H N O S. Calculated, %: C 60.66;
and 24 at a ratio of 1:1.3. The mixture was separated
by silica gel flash chromatography using methyl tert-
butyl ether–petroleum ether (1:4) as eluent.
–1
1
Dimethyl 3,4-diphenyl-4H-pyrazole-4,5-dicar-
boxylate (22). Yield 0.129 g (25%), colorless crystals,
mp 154–155°C; published data [24]: mp 150°C. UV
3
1
3
spectrum (MeOH): λ 313 nm (logε 4.03). IR spec-
max
C
–
1
4
trum, ν, cm : 3071 w, 2952 w, 1755 v.s, 1717 s,
516 m, 1497 m, 1443 s, 1350 s, 1227 s, 1196 s,
1
1
1157 s, 1007 w, 957 w, 814 w, 756 w, 691 s. H NMR
3
5
spectrum, δ, ppm: 3.69 s (3H, OMe), 3.87 s (3H,
OMe), 7.30–7.38 m (7H, Harom), 7.45–7.50 m (1H,
18
16
2
4
1
3
Harom), 7.96–7.98 m (2H, Harom). C NMR spectrum,
H 4.53; N 7.86; S 9.00.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016

REGIOSELECTIVITY OF THE THERMAL VAN ALPHEN–HÜTTEL REARRANGEMENT
-(4-Methylbenzenesulfonyl]-3,4-diphenyl-4H-
871
5
7.9 Hz), 7.70 t (1H, Harom, J = 7.4 Hz), 8.22 d (2H,
1
3
pyrazole-4-carbonitrile (27a). Yield 37%; the product
contained 15% of 28a. H NMR spectrum, δ, ppm:
H
arom, J = 7.4 Hz). C NMR spectrum, δ
C
, ppm: 94.0
1
4
(C ), 111.4 (CN), 125.4 (Carom), 125.6 (2C, Carom),
128.8 (2C, Carom), 129.3 (4C, Carom), 129.5 (2C, Carom),
129.7 (2C, Carom), 131.1 (Carom), 134.6 (Carom), 137.8 w
(Carom), 139.6 w (Carom), 150.3 (C ), 154.0 (C ). Found,
%: C 68.47; H 4.00; N 10.82; S 8.30. C22 S.
2
7
7
8
6
.40 s (3H, CH ), 7.24 t (4H, Harom, J = 8.1 Hz), 7.33–
3
.43 m (5H, Harom), 7.50 t (1H, Harom, J = 7.2 Hz),
.65 d (2H, Harom, J = 8.0 Hz), 7.86 d (2H, Harom, J =
5
3
1
3
.0 Hz).4 C NMR spectrum, δ , ppm: 21.7 (Me),
H N O
15 3 2
C
4.5 (C ), 111.0 (CN), 125.4 w (Carom), 125.6 w
Calculated, %: C 68.56; H 3.92; N 10.90; S 8.32.
(
(
Carom), 126.0 (2C, Carom), 129.0 (2C, Carom), 129.1
Carom), 129.3 (2C, Carom), 129.4 (2C, Carom), 130.0 (2C,
REFERENCES
Carom), 133.8 (Carom), 134.8 w (Carom), 146.5 w (Carom),
1
2
. Sammes, M.P. and Katritzky, A.R., Adv. Heterocycl.
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vol. 62, p. 491.
3
5
1
73.6 and 173.8 (C , C ). Found, %: C 69.18; H 4.21;
N 10.49; S 8.06. C H N O S. Calculated, %:
2
3
17
3
2
C 69.16; H 4.29; N 10.52; S 8.03.
3
-(4-Methylbenzenesulfonyl)-1,5-diphenyl-1H-
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–
1
1
993, vol. 25, p. 403.
cm : 2242 w (CN), 1501 m, 1339 s (SO , asym.),
2
1
6
157 v.s (SO , sym.), 1096 m, 791 m, 779 m, 706 m,
95 m, 660 m, 594 m, 536 m. H NMR spectrum, δ,
ppm: 2.46 s (3H, CH ), 7.22–7.28 m (4H, Harom), 7.34–
.46 m (8H, Harom), 8.10 d (2H, Harom, J = 8.2 Hz).
C NMR spectrum, δ , ppm: 21.7 (Me), 93.6 (C ),
11.3 (CN), 125.3 (Carom), 125.4 (2C, Carom), 128.6
2C, Carom), 129.1 (4C, Carom), 129.3 (Carom), 129.6
Carom), 130.2 (2C, Carom), 130.8 (Carom), 136.5 w
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5. Vasin, V.A., Masterova, Yu.Yu., Bezrukova, E.V.,
2
1
Razin, V.V., and Somov, N.V., Russ. J. Org. Chem.,
2
015, vol. 51, p. 874.
3
6. Komendantov, M.I. and Bekmukhametov, R.R., Chem.
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7
1
3
4
C
7
. Fedorov, A.A., Duisenbaev, Sh.E., Razin, V.V., Kuzne-
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1
(
(
(
5
8. Komendantov, M.I., Zavgorodnyaya, A.P., Dom-
nin, I.N., and Bekmukhametov, R.R., Zh. Org. Khim.,
3
1
54.1 (C ). Found, %: C 69.22; H 4.39; N 10.56;
S 8.11. C H N O S. Calculated, %: C 69.16; H 4.29;
1
986, vol. 22, p. 1541.
2
3
17
3
2
9. Bettinetti, G.F., Desimoni, G., and Grünanger, P., Gazz.
N 10.52; S 8.03.
-(Methanesulfonyl)-1,5-diphenyl-1H-pyrazole-
-carbonitrile (28b). Yield 90%, colorless crystals,
Chim. Ital., 1963, vol. 93, p. 150.
10. Heydt, H. and Regitz, M., Justus Liebigs Ann. Chem.,
1977, p. 1766.
3
4
–
1
mp 225–226°C. IR spectrum, ν, cm : 3021 w, 2924 w,
238 w, 1593 w, 1497 m, 1319 v.s, 1150 m, 775 m,
14 w, 698 m. H NMR spectrum (DMSO-d ), δ, ppm:
.32 s (3H, Me), 7.41–7.56 m (10H, Harom). C NMR
spectrum (DMSO-d ), δ , ppm: 43.1 (Me), 92.1 (C ),
11.3 (CN), 125.3 (Carom), 126.0 (2C, Carom), 129.0
2C, Carom), 129.38 (2C, Carom), 129.44 (2C, Carom),
29.9 (C ), 130.8 (Carom), 137.4 (Carom), 150.6 (C ),
52.2 (C ). Found, %: C 63.17; H 4.11; N 12.87;
11. Sharp, J.T., Findlay, R.H., and Thorogood, P.B.,
J. Chem. Soc., Perkin Trans. 1, 1975, p. 102.
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Fleming, J.S., and Seiler, S.M., J. Med. Chem., 1992,
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2
7
3
1
6
1
3
4
1
6
C
1
(
1
1
5
arom
3
14. Vo Quang, L. and Vo Quang, Y., Bull. Soc. Chim. Fr.,
974, p. 2575.
1
S 10.05. C H N O S. Calculated, %: C 63.14;
1
7
13
3
2
1
5. Snatzke, G. and Langen, H., Chem. Ber., 1969, vol. 102,
H 4.05; N 12.99; S 9.91.
-(Benzenesulfonyl)-1,5-diphenyl-1H-pyrazole-
-carbonitrile (28k). Yield 82%, colorless crystals,
p. 1865.
3
1
6. Vasin, V.A., Razin, V.V., Bezrukova, E.V., Koro-
vin, D.Yu., Petrov, P.S., and Somov, N.V., Russ. J. Org.
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4
–
1
mp 219–220°C. IR spectrum, ν, cm : 2253 w, 1501 m,
1
7
6
447 m, 1343 s, 1204 w, 1157 v.s, 1123 w, 1096 m,
91 m, 783 m, 748 m, 733 m, 706 m, 694 m, 683 m,
29 s, 598 m, 559 m, 540 m. H NMR spectrum, δ,
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1
8. Van Alphen, J., Recl. Trav. Chim. Pays–Bas, 1943,
1
vol. 62, p. 485.
ppm: 7.20–7.29 m (4H, Harom), 7.32–7.41 m (5H,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 6 2016