2-(2-Benzoylethynyl)-5-phenylpyrrole: Fixation of cis- and trans-rotamers in a crystal state

Article abstract of DOI:10.1070/MC2005v015n06ABEH002190

2-(2-Benzoylethynyl)-5-phenylpyrrole forms two crystal modifications with the carbonyl group oriented in cis- and trans-positions relative to the nitrogen atom thus representing the first example of the solid state stable rotamers around the C≡C bond system.

Full text of DOI:10.1070/MC2005v015n06ABEH002190

,
2005, 15(6), 229–232
2
-(2-Benzoylethynyl)-5-phenylpyrrole: fixation of cis- and trans-rotamers
in a crystal state
a
a
a
a
a
Boris A. Trofimov,* Zinaida V. Stepanova, Lubov N. Sobenina, Albina I. Mikhaleva, Lidia M. Sinegovskaya,
b
c
Konstantin A. Potekhin and Ivan V. Fedyanin
a
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk,
Russian Federation. Fax: + 7 3952 41 9346; e-mail: boris_trofimov@irioch.irk.ru
b
Vladimir State Pedagogical University, 600024 Vladimir, Russian Federation
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
c
Fax: +7 095 135 5085
DOI: 10.1070/MC2005v015n06ABEH002190
2
-(2-Benzoylethynyl)-5-phenylpyrrole forms two crystal modifications with the carbonyl group oriented in cis- and trans-posi-
tions relative to the nitrogen atom thus representing the first example of the solid state stable rotamers around the CºC bond
system.
The C-ethynylation of pyrroles remains a challenging synthetic
problem because the common Pd(Cu)-catalysed cross-coupling
a significant interference of the side reductive dehalogenation2(c)
also contribute to the problem.
1
Recently,5 we reported a basically novel ‘reverse’ cross-
coupling employing non-halogenated pyrroles and available
haloacetylenes. The reaction proceeds on the Al O surface at
of acetylenes with haloheteroarenes has been mainly limited by
1
,2
pyrroles with electron-withdrawing substituents, and N-sub-
2,3
stituted representatives. Instability of simpler halogenated
2
3
4
2(b)
pyrroles, their decreased reactivity in the cross-coupling and
room temperature requiring no palladium, copper, base and
Mendeleev Commun. 2005 229

,
2005, 15(6), 229–232
Br
N
Al O
– HBr
2
3
room temperature
H O
N
H
Br
O
1
2
3
NH
O
N
H
N
N
O
H
H O
4
a
4b
4
5
Scheme 1
solvent, as here exemplified by the ethynylation of 2-phenyl-
pyrrole 1 with 1-benzoyl-2-bromoacetylene 2 (Scheme 1). The
yield of 2-(2-benzoylethynyl)-5-phenylpyrrole 4 in this par-
ticular experiment was 69% (50% in preliminary report ). Inter-
mediate 3, side adduct 5 and their homologues with other
substituents were identified previously.5
Unexpectedly, ethynylpyrrole 4 was found to crystallise in
two visually distinctive forms: prisms 4a and needles 4b with
different melting points (173–174 and 192–194 °C, respectively).†
The prisms of 4a are less stable and, upon repeated recrys-
tallization, transform to the needles of 4b, which do not give
prisms when further recrystallised. The latter can only be isolated
by the instant extraction of the alumina used in the reaction.
‡
The X-ray analysis (Figures 1 and 2) revealed that the crys-
†
5
tals represent the cis- (4a) and trans- (4b) rotamers with respect
to mutual disposition of the nitrogen atom and the carbonyl
group (Scheme 1). The bond lengths and angles in the vicinity
of the triple bond do not remarkably differ from the common
values, with the triple bond length corresponding to the normal
6
(1.202±0.005 Å): 1.203 and 1.201 Å for 4a and 4b, respec-
tively. The C=O bonds are slightly longer than usual: 1.228 Å
6
for 4a and 1.230 Å for 4b against 1.215 Å, while both Csp2–Csp
bonds are considerably shorter: 1.431, 1.411 Å for 4a and 1.441
†
2
-Phenylpyrrole 1 (72 mg, 0.5 mmol) and 1-benzoyl-2-bromoacety-
6
and 1.401 Å for 4b against 1.459 Å. The C≡C bonds are bent
lene 2 (105 mg, 0.5 mmol) were triturated in a mortar with 3.6 g of
toward the C=O bonds: 176.33°, 173.73° for 4a and 179.8(3)°,
Al O (Chemapol L 40/250 µ, pH 9.8) at room temperature. In 1 min,
2
3
173.2(2)° for 4b, whereas the angles at the C=O group are dis-
the reaction powder turned bright yellow to change in 10 min to yellow
orange with the temperature rising by 5 °C. After 45 min, the mixture
was washed on a glass filter with n-hexane (3×40 ml) to get rid of
the starting compounds and intermediates. The reaction products were
torted toward the C≡C bond: 122.01° for 4a and 122.1° for 4b,
with some angle decrease from the benzene ring side: 116.65°
for 4a and 116.1° for 4b.
extracted by an n-hexane–Et O (2:1) mixture (3×50 ml), and three
For 4a, the torsion angle between the pyrrole and 5-phenyl
planes is ~10° and that between the benzoyl is ~17°, whereas in
the molecule of 4b these structural units are essentially planar
2
fractions were collected. After partial evaporation of the solvents in air,
from the first fraction, a mixture of small orange crystals (mp 176–179 °C)
and single needles (mp 184–186 °C) of 2-(2-benzoylethynyl)-5-phenyl-
pyrrole 4 (65 mg) was isolated. From the mother solution, the dark red
needles (mp 202–203 °C) of 1,1-di(5-phenylpyrrol-2-yl)-2-benzoyl-
ethene 5 (3 mg) were precipitated. Upon standing overnight, the dark
orange prisms from the second fraction and the needles of the same
colour from the third fraction were precipitated. The crystals were
washed with n-hexane to obtain 14 mg (10%) of dark orange prisms
(
~7° and 0°, respectively), that is likely meant a stronger con-
jugation in the latter. The crystal packing of the two forms are
entirely different: the prisms of 4a consist of H-bonded macro-
cyclic dimers (Figure 3), while the needles of 4b are H-bonded
chains (Figure 4).
O(1)
(
mp 173–181 °C) and 15 mg (11%) of dark orange red shining slim
C(16)
C(7)
C(6)
H(1)
N(1)
needles (mp 183–184 °C). The total yield of 4 was 94 mg (69%).
From microscopic examination, it is seen that upon melting the prisms
or small crude crystals, part of the material is transformed into small
needles at 162–172 °C, which further melt at 182–185 °C.
Pure samples of the crystals melt as follows: the prisms (designated
as 4a): 173–174 °C; the needles (designated as 4b): 192–194 °C (re-
crystallization twice from benzene), 191–193 °C (ethanol–water, 2:1),
C(13)
C(17)
C(18)
C(15)
C(14)
C(5)
C(8)
C(12)
C(11)
C(9)
C(10)
C(4)
C(1)
C(2)
C(19)
C(3)
1
84–186 °C (n-hexane–Et O, 2:1).
Figure 1 The general view of 4a. Selected bond lengths (Å): C(7)–O(1)
1.2284(16), C(5)–C(6) 1.2026(19), C(7)–C(6) 1.431(2), C(1)–C(5) 1.411(2),
N(1)–H(1) 0.904(15); selected bond angles (°): C(6)–C(5)–C(1) 176.33(16),
C(5)–C(6)–C(7) 173.73(15), C(6)–C(7)–C(8) 116.65(12), C(6)–C(7)–O(1)
122.01(13).
2
1
4
a: H NMR (400 MHz, CDCl ) d: 9.07 (br. s, 1H, NH), 8.16 (m, 2H,
3
H COPh), 7.58 (m, 1H, H COPh), 7.50 (m, 4H, H COPh, H Ph-5),
o
p
m
o
3
7
.40 (m, 2H, H Ph-5), 7.29 (m, 1H, H Ph-5), 6.91 (dd, 1H, H-3, J 3.6 Hz,
m
p
4
3
4
13
J 2.5 Hz), 6.56 (dd, 1H, H-4, J 3.6 Hz, J 2.8 Hz). C NMR (100 MHz,
CDCl ) d: 177.67 (C=O), 137.56 (C-5 of pyrrole), 136.90 (C COPh),
3
i
C(16)
1
33.98 (C COPh), 130.85 (C Ph-5), 129.45 (C COPh), 129.26 (C Ph-5),
C(11)
p
i
o
m
1
28.60 (Cm COPh), 128.08 (C Ph-5), 124.72 (C Ph-5), 122.64 (C-3 of
C(15)
p
o
C(10)
C(9)
C(17)
C(12)
C(13)
pyrrole), 110.87 (C-2 of pyrrole), 108.40 (C-4 of pyrrole), 93.38 (Cα),
8
8.88 (C ). Found (%): C, 83.81; H, 5.00; N, 5.24. Calc. for C H NO
β
19 13
H(1)
N(1)
(
%): C, 84.11; H, 4.83; N, 5.16.
C(18)
C(14)
1
4
b: H NMR (400 MHz, CDCl ) d: 8.98 (br. s, 1H, NH), 8.16 (m, 2H,
3
C(19)
C(8)
C(7)
H COPh), 7.59 (m, 1H, H COPh), 7.49 (m, 4H, H COPh, H Ph-5),
C(4)
C(5)
o
p
m
o
3
7
.40 (m, 2H, H Ph-5), 7.29 (m, 1H, H Ph-5), 6.92 (dd, 1H, H-3, J 3.6 Hz,
m
p
C(3)
4
3
4
13
C(1)
C(2)
C(6)
J 2.5 Hz), 6.58 (dd, 1H, H-4, J 3.6 Hz, J 2.8 Hz). C NMR (100 MHz,
CDCl ) d: 177.70 (C=O), 137.60 (C-5 of pyrrole), 136.92 (C COPh),
O(1)
3
i
1
33.95 (C COPh), 131.00 (C Ph-5), 129.46 (C COPh), 129.25 (C Ph-5),
p i o m
128.66 (Cm COPh), 128.06 (C Ph-5), 124.75 (C Ph-5), 122.65 (C-3 of
p
o
Figure 2 The general view of 4b. Selected bond lengths (Å): C(7)–O(1)
1.230(3), C(5)–C(6) 1.201(3), C(7)–C(6) 1.441(3), C(1)–C(5) 1.401(3),
N(1)–H(1) 0.976; selected bond angles (°): C(6)–C(5)–C(1) 179.8(3), C(5)–
C(6)–C(7) 173.2(2), C(6)–C(7)–C(8) 116.1(2), C(6)–C(7)–O(1) 122.1(2).
2
30 Mendeleev Commun. 2005

,
2005, 15(6), 229–232
Br
a
c
N
0
H...O
3
Al2O3 – HBr
b
N
O
H
N
Figure 3 The H-bonded macrocyclic dimers in the crystal structure of 4a.
H
O
§
The crystals of 4a and 4b have different IR spectra (in KBr
–1
pellets, n/cm ); the major differences occur in the following
regions: (ν ) 3311 for 4a and 3332 for 4b; (νCO) 1630 (s),
NH
1
4
617 (sh, m) for 4a, 1623 (s), 1610 (s) for 4b; (δ≡C–) 650 (s) for
a, 651 and 647 (m) for 4b.
–
3
2×4a
However, in solution (CCl , 50–2 mmol dm ) these differ-
4
ences disappear and only a higher intensity of the C=O absorp-
–
1
tion [1637 cm (s) for both 4a and 4b] and a slight lower
4
b
Scheme 2
c
frequency shift of the bound NH are observed for 4a as com-
pared to those of 4b [3306 cm–1 (s) for 4a and 3312 cm (w)
for 4b]. In the UV-VIS spectra (in cyclohexane), the absorption
maxima are the same for both crystals, though they are all
systematically more intense for 4b [lmax/nm (lg e for 4a, 4b)]:
–1
0
b
2
18 (sh) (4.04, 4.13), 237 (3.91, 4.02), 269 (4.23, 4.31), 286 (sh)
4.14, 4.22), 385 (4.52, 4.58), reproducibility of the lg e value
being within 2–4% (from three concentrations).
(
a
1
13
The H and C NMR spectra are identical for both crystals in
accordance with the expected low-rotation barrier between the two
rotamers. Indeed, the B3LYP/6-311G(d) calculations (the detailed
account of the calculations, including those of vibrational spectra
for both rotamers will be published elsewhere) of isolated mole-
cules gave the total energy difference of 0.77 kcal mol–1 in favour
Figure 4 The H-bonded chains in the crystal structure of 4b.
‡
–1
XRD data for 4a and 4b.
At 190 K, crystals of 4a (C H NO) are monoclinic, space group
P2 /c, a = 9.367(3), b = 15.704(5) and c = 10.592(2) Å, b = 116.15(3)°,
of 4b with the 4b ® 4a barrier equal to 2.6 kcal mol . Upon
1
9
13
thin layer chromatography (Alufol; eluent: n-hexane–Et O, 2:1)
2
1
the crystals of 4a and 4b showed the same R (0.39).
f
3
–3
V = 1398.5(7) Å , Z = 4, M = 271.30, d = 1.289 g cm , m(MoKα) =
calc
All the data obtained can be rationalised as follows: cis-rotamer
a is likely originated from an alumina-induced cis-elimination
–
1
=
0.80 cm , F(000) = 568.
4
At 120 K, crystals of 4b (C H NO) are orthorhombic, space group
1
9
13
in intermediate 3 with immediate stabilization of the cis-oriented
N–H and C=O bonds in macrocyclic dimer 2×4a, which then
further transforms to H-chained 4b.
3
Pna21,
Z
a
M
= 10.684(4),
= 271.30, dcalc = 1.307 g cm ,
Intensities of 3601 (4a) or 9690 (4b) reflections were measured with
a Syntex P21 [l(MoKα) = 0.71072 Å, q/2q-scans, 2q < 54°] or Smart
000 CCD [l(MoKα) = 0.71072 Å, w-scans, 2q < 52°] diffractometer
and 3404 (4a) or 2653 (4b) independent reflections [R = 0.0548 (4a),
b = 23.336(11) and c = 5.5288(16) Å, V = 1378.5(9) Å ,
–
3
–1
= 4,
m(MoKα) = 0.81 cm , F(000) = 568.
Thus, the fixation of cis- and trans-rotamers 4a and 4b is
likely due to the strong H-bonding in the crystal state, which
keeps retaining for a while in solution.
1
int
0
.0447(4b)] were used in a further refinement. The structures were solved
Recently, a crystalline diacetylene, 1,4-di(α-naphthyl)-1,3-
7
by a direct method and refined by the full-matrix least-squares technique
butadiyne, was found to adopt a centrosymmetric conformation
of the naphthalene rings around the –C≡C–C≡C– axis. However,
the corresponding cis-rotamer has not been detected.
2
against F in the anisotropic–isotropic approximation. Hydrogen atoms
except H(1) were included in calculated positions and refined as riding
atoms, H(1) atoms were located from the Fourier synthesis and refined
in the isotropic approximation. The refinement converged to: wR =
2
This work was supported by the Russian Foundation for Basic
Research (grant no. 05-03-32289).
=
0.0831 and GOF = 0.973 [R = 0.0402 for 1946 observed reflections
1
with I > 2s(I)] for 4a; wR = 0.0895 and GOF = 1.005 [R = 0.0440 for
2
1
2
160 observed reflections with I > 2s(I)] for 4b. All calculations were
performed using SHELXTL PLUS 5.1.
References
1
L. Brandsma, S. F. Vasilevsky and H. D. Verkruijsse, Application of
Transition Metal Catalysts in Organic Synthesis, Springer, Berlin, 1998,
pp. 178–226.
(a) S. F. Vasilevskii, T. A. Sundukova, M. S. Shvartsberg and I. L. Kot-
lyarevskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1661 (Bull. Acad.
Sci. USSR, Div. Chem. Sci., 1979, 28, 1536); (b) S. F. Vasilevskii,
T. A. Sundukova, M. S. Shvartsberg and I. L. Kotlyarevskii, Izv. Akad.
Nauk SSSR, Ser. Khim., 1980, 1871 (Bull. Acad. Sci. USSR, Div. Chem. Sci.,
2
1980, 29, 1346); (c) T. A. Sundukova, S. F. Vasilevskii, M. S. Shvartsberg
and I. L. Kotlyarevskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1980, 726
(Chem. Abstr., 1980, 93, 71446f).
3 A. Alvarez, A. Guzman, A. Ruiz, E. Velarde and J. M. Muchowski,
J. Org. Chem., 1992, 57, 1653.
Mendeleev Commun. 2005 231

,
2005, 15(6), 229–232
4
(a) A. Gossauer, Die Chemie der Pyrrole, Springer, New York, 1974,
pp. 326–332; (b) R. A. Jones and G. P. Bean, in The Chemistry of Pyrroles.
Organic Chemistry. A Series of Monographs, eds. A. T. Blomquist and
H. H. Wasserman, Academic Press, New York, 1977, pp. 129–140;
5 B. A. Trofimov, Z. V. Stepanova, L. N. Sobenina, A. I. Mikhaleva and
I. A. Ushakov, Tetrahedron Lett., 2004, 34, 6513.
6 A. J. Gordon and R. A. Ford, The Chemist’s Companion. A Handbook of
Practical Data, Techniques and References, Wiley, New York, 1972.
7 J. G. Rodriquez and J. L. Tejedor, Tetrahedron, 2005, 61, 3033.
(c) A. Gossauer, in Methoden der Organischen Chemie (Houben-Weil),
Bd. E6a. Hetarene I. Hrsg, ed. R. P. von Kreher, Thieme, New York, 1994,
Teil 1, S. 750; (d) L. Brandsma, S. F. Vasilevsky and H. D. Verkruijsse,
Application of Transition Metal Catalysts in Organic Synthesis, Springer,
Berlin, 1998, p. 34.
Received: 24th May 2005; Com. 05/2516
2
32 Mendeleev Commun. 2005