Reactions of 2-phenylpyrrole with bromobenzoylacetylene on metal oxides active surfaces

Article abstract of DOI:10.1016/j.tet.2008.03.104

The solvent-free interaction of 2-phenylpyrrole with bromobenzoylacetylene (room temperature) upon their grinding with solid metal oxides (MgO, CaO, ZnO, BaO, Al₂O₃, TiO₂, ZrO₂) and salts (CaCO₃, ZrSi

Full text of DOI:10.1016/j.tet.2008.03.104

Tetrahedron 64 (2008) 5541–5544
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Reactions of 2-phenylpyrrole with bromobenzoylacetylene
on metal oxides active surfaces
,
a
a
a
Boris A. Trofimova , Lyubov’ N. Sobenina , Zinaida V. Stepanova , Tamara I. Vakul’skaya ,
*
Ol’ga N. Kazheva b, Grigorii G. Aleksandrovc, Oleg A. Dyachenko b, Al’bina I. Mikhaleva a
a A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Street, 664033 Irkutsk, Russian Federation
b Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 Academician Semenov Street, 142432 Chernogolovka, Russian Federation
c NS Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 31 Leninskii Prosp., 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
The solvent-free interaction of 2-phenylpyrrole with bromobenzoylacetylene (room temperature) upon
their grinding with solid metal oxides (MgO, CaO, ZnO, BaO, Al2O3, TiO2, ZrO2) and salts (CaCO3, ZrSiO4)
leads to either the cross-coupling product or the adduct of pyrrole addition to the riple bond of acetylene.
The ethynylation is accompanied by the formation of intermediate and side products: E-2-(1-bromo-2-
benzoylethenyl)-5-phenylpyrrole and 1,1-di(5-phenylpyrrol-2-yl)-2-benzoylethene. The activity of the
metal oxides in the ethynylation reaction falls in the order (in the brackets, the content of 2-benzoyl-
ethynyl-5-phenylpyrrole in the reaction mixture is given): ZnO (81%), BaO (73%), Al2O3 (71%), MgO (69%),
CaO (50%). The oxides, SiO2, TiO2, ZrO2, and the salts, CaCO3 and ZrSiO4, are inactive in the ethynylation
reaction affording only the intermediate adduct, with ZrO2 the isolated yield of the bromoethenylpyrrole
reaching 60%. ESR monitoring shows the reaction to start from one electron transfer from pyrrole to
acetylene mediated by the oxide surface. The adduct is readily converted on Al2O3 to 2-(benzoylethynyl)-
5-phenylpyrrole crystallized mostly as cis-rotamer (X-ray data).
Received 22 November 2007
Received in revised form 11 March 2008
Accepted 27 March 2008
Available online 3 April 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
application of the active surfaces including their modifications is
steadily spreading, a testimony to their unfolding potential.3
Recently, we have reported the direct ethynylation of pyrroles
and indoles with electron deficient haloacetylenes on the Al2O3
active surface. This reactions proceed rapidly at room temperature
with no transition-metal catalyst and base under solvent-free
conditions, and require no preliminary functionalization of the
pyrrole and indole nuclei.1 The reaction paves the way to earlier
inaccessible pyrroles and indoles with functionalized acetylenic
substituents, useful building blocks to design drugs, and new
materials for molecular electronics.
This paper aims to elucidate whether alumina is the unique
metal oxide to affect the ethynylation and whether other active
surfaces for this reaction can be found.
Today, the active surfaces such as metal oxides play an ever-
growing role in organic synthesis and are widely employed not only
for preparative organic reactions but also in industry. Such
reactions normally proceed under mild conditions, with high
chemo-, regio-, and stereoselectivity, securing simpler isolation
procedures compared to similar reactions in solution.2 The scope of
2. Results and discussion
Herein, we have investigated the room temperature interaction
of 2-phenylpyrrole with bromobenzoylacetylene upon their
grinding with diverse metal oxides and salts (10-fold amount) as
active surfaces (Table 1). The reaction course (conversion of
reactants 1 and 2 and the ratio of products) was determined from
the 1H NMR spectra of the CDCl3 extracts from the reaction mixture.
This reaction has been chosen as a standard of the pyrrole
ethynylation with haloacetylenes.
As reported,1 this reaction when carried out on Al2O3 gave
ethynylpyrrole 3 as a major product and small amounts of the
intermediate 4 and the side product 5 (Scheme 1).
Apart from signals of these compounds, in the 1H NMR spectra
of the samples taken from the reaction mixtures appear two broad
singlets at 5.70 and 12.44 ppm. According to 1H and 13C NMR
spectroscopic data, these signals are assigned to unstable dipyrro-
lylbromoethane 6, which was not possible to isolate. This product
likely results from nucleophilic addition of pyrrole 1 onto the
intermediate bromoethenylpyrrole 4 (Scheme 2).
* Corresponding author. Tel.: þ7 3952 461411/511431; fax: þ7 3952 419346.
E-mail address: boris_trofimov@irioch.irk.ru (B.A. Trofimov).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.104

5542
B.A. Trofimov et al. / Tetrahedron 64 (2008) 5541–5544
Table 1
the active surfaces are equally contaminated with the same tran-
sition metals.
1H NMR spectroscopic monitoring of reaction of 2-phenylpyrrole 1 with bromo-
benzoylacetylene 2 (room temperature)
As the case of Al2O3,1 the cross-coupling is accompanied by the
formation of bromoethenylpyrrole 4 and dipyrrolylethene 5, the for-
mer being an intermediate and the latter a side product (Scheme 1).
The metal oxides (TiO2, ZrO2) as well as SiO2 and the salts
(CaCO3, ZrSiO4) are found inactive in the cross-coupling. Instead,
they happen to be highly active in the nucleophilic addition of
pyrrole 1 to the triple bond of bromobenzoylacetylene 2 to afford
the adduct 4 (the content of which in the reaction mixture ranges
from 81% up to 88%) (Scheme 3).
Active surface
Time of reaction, min
10
60
Compositiona of reaction mixture, %
1
3
4
5
6
1
3
4
5
6
MgO
CaO
ZnO
BaO
Al2O3 (pH 7.5)
Al2O3 (pH 9.3)
Al2O3b (pH 9.3)
SiO2
TiO2
ZrO2
54
71
0
41
19
78
69
62
62
61
0
0
0
0
0
5
7
0
3
4
4
0
0
5
0
0
0
0
0
0
0
0
0
0
0
0
16
21
27
41
32
25
39
0
0
5
6
12
0
0
0
69
50
81
73
71
68
68
0
0
0
0
0
6
9
0
2
4
6
0
0
0
0
13
0
0
0
0
0
0
0
0
12
0
17
0
18
20
21
21
20
80
70
73
59
61
15
20
23
26
20
88
87
83
81
85
7
17
17
14
4
9
0
Br
O
AS
N
H
+
Br
N
H
4
O
2
CaCO3
ZrSiO4
0
7
0
0
19
0
1
15
a
The percentage of acetylene 2 in the reaction mixture corresponds to the content
AS = SiO2 , TiO2 , ZrO2 ,CaCO3 , ZrSiO4
of pyrrole 1.
b
Scheme 3.
K2CO3 (5% relative to alumina) was used.
Thus, these metal oxides and salts are specific active surfaces for
effecting chemo-, regio-, and stereoselective addition of pyrrole 1
(by its C-2-position) to the triple bond of acetylene 2.
In all cases, dipyrrolylethene 5 is formed in much smaller
amounts (0–19%). This is obviously the product of substitution of
the bromine atom in the intermediate 4 by the pyrrolyl moiety
(Scheme 4).
We have also observed the formation of adduct 6 in the CDCl3
solution (1H NMR spectroscopy) directly from pyrrole 1 and acet-
ylene 2. However, evaporation of the solvent gives a solid residue of
a complex unidentifiable structure.
For the first time it is shown (Table 1) that certain metal oxides
are active media for the interaction studied, particularly ZnO and
BaO, the activity of which surpasses that of Al2O3. The content of
the ethynylation product in the reaction mixture is 81% (ZnO), 73%
(BaO), and 71% (Al2O3).
No direct dependence of the oxide efficiency in the cross-cou-
pling on the basicity is observed as follows from Table 1 (i.e., ZnO is
a weaker base than CaO but shows much higher activity in the
cross-coupling). Moreover, alumina of different basicity, even with
K2CO3 additive, gives practically the same results. One may suppose
that transition-metal contaminations of the above metal oxides and
salts influence the reaction studied. However, this does not agree
with the practically similar results obtained with different metal
oxides (MgO, CaO, ZnO, BaO, Al2O3, Table 1). It is improbable that all
Br
N
H
N
N
H
H
N
H
1
O
- HBr
O
4
5
Scheme 4.
Apparently, the cross-coupling, resulting in the formation of the
ethynylpyrrole 3, proceeds via the intermediate 4, which further
eliminates HBr. This is supported by the observation that when the
intermediate 4 (prepared on ZrO2) is passed through an Al2O3
column the ethynylpyrrole 3 is isolated. It is noteworthy that in this
case the pyrrole 3 crystallized mostly as its cis-rotamer (prisms)
(Fig. 1).
O
Al2O3
+
Br
O
N
H
N
H
3
2
1
Br
O
N
H
N
H
N
H
N
H
N
H
+
+
O
O
O
4
5
Previously, this type of isomerism of the CspꢀCsp3 bond in the
crystalline state for the same compound was noted briefly,1b where
both cis-rotamer and trans-rotamer (needles) were isolated.
Scheme 1.
Br
N
Br
H
N
H
N
H
O
N
H
CDCl3
+
O
4
1
6
Scheme 2.

B.A. Trofimov et al. / Tetrahedron 64 (2008) 5541–5544
5543
Figure 1. General view of 2-(2-benzoylethynyl)-5-phenylpyrrole 3.
X-ray analysis data for a new polymorphous modification of
ethynylpyrrole 3, given in Section 3, correlate well with the data
obtained earlier for cis-rotamer.1b
Obviously, the route to ethynylpyrrole 3 via the charge-transfer
complex 7 and further the salt 8 avoiding the adduct 4 has not been
excluded (Scheme 5). Such a reaction may be realized as a parallel
or complementary channel of the above HBr elimination from the
adduct 4.
O
Figure 2. ESR spectra of dry reaction mixture of 2-phenylpyrrole/bromobenzoylace-
tylene/TiO2, recorded under different microwave power.
Br
1
+
2
N
H
deliver the ion–radical pair. Depending on acid–base properties
of the active surface the ion-pair components behave diversely: on
the acidic surfaces the radical cation should be stabilized, while on
the basic ones it is deprotonated to a neutral radical, thus leading to
different reaction products 3 and 4, respectively.
Thus, the experimental data point to the fact that ethynylation
of pyrroles with bromobenzoylacetylene may involve a one-elec-
tron transfer stage delivering ion–radicals stabilized by the crys-
talline lattice of the active surface.
7
+
O
O
N
H
N
H
8
Br
3
Scheme 5.
The active surface participation in the ion–radical generation is
also confirmed by the appearance of the corresponding but very
weak signals in ESR spectra of the separated pairs: Al2O3–2-phe-
nylpyrrole and Al2O3–bromobenzoylacetylene. Thus, approxi-
mately 0.5 h after preparation, 2-phenylpyrrole on Al2O3 turns
beige. In the ESR spectrum appears a weak (3ꢁ1014 spin/g) broad
(1.1 mT) singlet with g-factor 2.0024, narrowing and increasing
with time. Bromobenzoylacetylene on Al2O3 just after the prepa-
ration becomes pink and its ESR spectrum shows very weak
(1014 spin/g) and narrow (0.33 mT) singlet with g-factor 2.0032,
which does not practically change with time.
In conclusion, a novel approach for the direct room temperature
chemo-, regio-, and stereoselective C-2-ethynylation and -ethenyl-
ation of pyrroles with haloacetylenes on metal oxides’ and salts’
active surfaces under transition-metal and solvent-free conditions
has been generalized for the first time. New active surfaces such as
metal oxides and salts have been found to be effective for the above
reactions. The reaction follows one-electron transfer mechanism to
form ion–radical intermediates stabilized by the metal oxide active
surfaces. The new concept contributes to both synthetic pyrrole and
acetylene chemistry.
It is known that reactions on the metal oxide surfaces often
proceed by one-electron transfer and hence for an investigation of
their mechanisms, the ESR technique is appropriate.4
We have monitored the reaction between the pyrrole 1 and
acetylene 2 on active surfaces of the oxides: ZnO, Al2O3 (pH 9.5),
SiO2, TiO2, ZrO2 and the salts: CaCO3, ZrSiO4 by the ESR technique
and found singlets with g-factors in the region of free radicals
(Table 2).
The value of g-factors changes depending on the surface nature
and varies within 0.0006. The asymmetric signals detected for
ZrSiO4, TiO2, and ZrO2 under microwave power saturation split in
two lines (Fig. 2).
The line with g-factor 2.0023 is assigned to the 2-phenylpyrrole
cation–radical. The second line with g-factors 2.0032–2.0044
(depending on active surface nature) is likely to be attributed to the
complex of bromobenzoylacetylene anion–radical with active sur-
face. At the same time, microwave power saturation applied to the
reaction mixtures on oxides Al2O3 and ZnO does not cause the ESR
signal splitting. Probably, the components of the reaction mixture
activated by the crystal lattice first undergo charge transfer to
Table 2
3. Experimental
3.1. General
ESR signal characteristics for the reaction of 2-phenylpyrrole with bromobenzoyl-
acetylene on active surfaces
Active surface
Nꢁ1016, spin/g
g-Factor
DH, mT
ZnO
35
10
2.0030
2.0026
2.0028
2.0030
2.0027
2.0024
2.0024
0.660
0.600
0.600
0.533
0.710
0.622
0.580
1H (400.13 MHz) and 13C (101.6 MHz) NMR spectra were recor-
ded on a ‘Bruker DPX250’ instrument with CDCl3 as solvent and
HMDS as the internal standard. The assignment of signals in the 1H
NMR spectrum was made using COSY and NOESY experiments.
Resonance signals of carbon atoms were assigned based on HSQC
and HMBC experiments.
Al2O3 (pH 9.5)
SiO2 (Merck)
CaCO3
TiO2
ZrO2
7.0
6.9
11
4.0
8.7
ZrSiO4

5544
B.A. Trofimov et al. / Tetrahedron 64 (2008) 5541–5544
porcelain mortar with ZrO2 (3.5 g, 10-fold amount) at ambient
X-ray diffraction study of 3 was carried out with an Enraf–
Nonius CAD-4 diffractometer at room temperature ( /2 -scanning,
Mo K radiation, graphite monochromator). Crystalline structure
temperature for 1 h. The mixture self-heated up to 30 ꢂC and
became bright yellow. Gradually the color changed to brown.
The reaction mixture was placed on the column with ZrO2 and
eluted with hexane to afford 0.211 g (60%) of 2-(1-bromo-2-
benzoylethenyl)pyrrole 4.
u
q
a
was solved by direct methods followed by Fourier synthesis using
SHELXS-97.5a All non-hydrogen atoms were refined using aniso-
tropic full-matrix approximation using SHELXL-97.5b Coordinates
of hydrogen atoms were defined experimentally and refined
isotropically. Atom coordinates, bond lengths, and angle values
were deposited at Cambridge Crystallographic Data Center (CCDC).
These data are available via www.ccdc.cam.uk/conts/retrie-
ving.html (or from CCDC, 12 Union Road, Cambridge CB2 1EZ, UK;
fax: þ44 (0) 1223 336 033; or e-mail: deposit@ccdc.cam.ac.uk). Any
request to the CCDC for data should quote the full literature citation
and CCDC reference number 678754.
B Equimolar amounts of pyrrole (0.143 g, 1 mmol) and bromo-
benzoylacetylene (0.209 g, 1 mmol) were regularly grinded in
porcelain mortar with ZrO2 (3.5 g, 10-fold amount) at ambient
temperature for 1 h. The mixture self-heated up to 30 ꢂC and
became bright yellow. Gradually the color changed to brown.
The reaction mixture was placed on the column with Al2O3 and
eluted with hexane and then with diethyl ether to afford
0.042 g (12%) of 2-(1-bromo-2-benzoylethenyl)pyrrole
(hexane) and 0.176 g (65%) of 2-benzoylethynylpyrrole
(diethyl ether).
4
3
Crystal and experimental data: C19H13NO, M¼271.30, monoclinic,
C2/c, a¼16.748(3) Å, b¼7.225(1) Å, c¼23.818(5) Å,
b
¼97.78(3)ꢂ,
V¼2855.6(1) Å3, Z¼8, Dcalcd¼1.26 g cmꢀ3
,
m
¼0.078 mmꢀ1
, re-
flections observed/independent 4507/3094, 243 parameters refined,
3.3.1. 3-Bromo-1-phenyl-3,3-bis(5-phenyl-1H-
R¼0.037 for 1841 reflections with [F0>4
s(F0)].
pyrrol-2-yl)-1-propanone (6)
The crystal structure is formed by one crystallographic in-
dependent molecule (Fig. 1), taking general position in the unit cell.
The molecule has practically plane conformation and dihedral an-
gles formed by planes of pyrrole and phenyl cycles C(15)C(16)/
C(20) and C(9)C(10)/C(14) are 11.9 and 2.9ꢂ, respectively. Dihedral
angle between planes of phenyl cycles is 11.1ꢂ. Angles C(5)–C(6)–
C(7) and C(6)–C(7)–C(8) of acetylene moiety is equal to 175.6(1)
and 178.4(1)ꢂ, correspondingly.
1H NMR (CDCl3)
d 12.44 (br s, 2H, NH), 8.23 (m, 2H, Ho COPh),
8.11 (m, 4H, Ho 5-Ph), 7.45–7.30 (m, 9H, Hm, Hp Ph, COPh), 7.36 (br s,
2H, H-3), 6.90 (br s, 2H, H-4), 5.70 (br s, 2H, CH2); 13C NMR (CDCl3)
d
195.5 (C]O), 153.2 (C5), 142.3 (Ci COPh), 136.4 (C2), 135.7 (Ci Ph),
133.7 (Cp COPh), 131.1 (C3), 129.4 (Co COPh), 128.9 (Cm Ph), 128.7 (Cm
COPh), 128.3 (Cp Ph), 128.1 (Co Ph), 124.7 (C–Br), 117.0 (C4), 46.2
(CH2).
The molecules form piles along axis b. The disposition of mol-
ecules relative to each other is favorable to the occurrence of
strongly shortened intermolecular interactions N(1)–H(1)/O(1).
Bond lengths N(1)–H(1) and H(1)/O(1) is equal to 0.92(1) and
1.98(2) Å, respectively, and angle N(1)–H(1)/O(1) is 172(1)ꢂ. Sum
of van-der-Waals radii of the H/O atoms is 2.45 Å.6
ESR spectra were recorded at room temperature using an SE/
X-2547 Radiopan (Poland) spectrometer equipped with a magne-
tometer and a high frequency gauge. Concentrations of para-
magnetic centers were calculated by known techniques.7
Acknowledgements
This work was supported by the Russian Foundation for Basic
Research (grant no 05-03-32289).
References and notes
1. (a) Trofimov, B. A.; Stepanova, Z. V.; Sobenina, L. N.; Mikhaleva, A. I.; Ushakov, I.
A. Tetrahedron Lett. 2004, 45, 6513–6516; (b) Trofimov, B. A.; Stepanova, Z. V.;
Sobenina, L. N.; Mikhaleva, A. I.; Sinegovskaya, L. M.; Potekhin, K. A.; Fedyanin,
I. V. Mendeleev Commun. 2005, 6, 229–232; (c) Trofimov, B. A.; Sobenina, L. N.;
Stepanova, Z. V.; Demenev, A. P.; Mikhaleva, A. I.; Ushakov, I. A.; Vakul’skaya, T.
I.; Petrova, O. V. Zh. Org. Khim. 2006, 42, 1348–1355; (d) Sobenina, L. N.;
Demenev, A. P.; Mikhaleva, A. I.; Ushakov, I. A.; Vasil’tsov, A. M.; Ivanov, A. V.;
Trofimov, B. A. Tetrahedron Lett. 2006, 47, 7139–7141; (e) Trofimov, B. A.;
Sobenina, L. N.; Demenev, A. P.; Stepanova, Z. V.; Petrova, O. V.; Ushakov, I. A.;
Mikhaleva, A. I. Tetrahedron Lett. 2007, 48, 4661–4664.
2. (a) McKillop, A.; Young, D. W. Synthesis 1979, 401–422, 481–500; (b) Ranu, B. C.;
Bhar, S.; Chakraborty, R.; Das, A. R.; Saha, M.; Sarkar, A.; Chakraborti, R.; Sarkar,
D. C. Indian Inst. Sci. 1994, 74, 15–33; (c) Basyuk, V. A. Russ. Chem. Rev. 1995, 64,
1003–1020; (d) Banerjee, A. K.; Mimo, M. S. L.; Vegas, W. J. V. Russ. Chem. Rev.
2001, 70, 971–990.
3.2. The reaction of 2-phenylpyrrole 1 with bromo-
benzoylacetylene 2 on active surface: typical procedure
Equimolar amounts of pyrrole (0.143 g, 1 mmol) and bromo-
benzoylacetylene (0.209 g, 1 mmol) were regularly grinded in
porcelain mortar with active surface (3.5 g, 10-fold amount) at
ambient temperature for 1 h. The reaction was monitored using 1H
NMR (CDCl3) technique (samples were taken from the reaction
mixture in 10 and 60 min). The ratio of the reaction products was
determined by the integral intensity of signals of H-atoms: H-3, H-4
for pyrrole 1 (6.29 and 6.51 ppm), pyrrole 3 (6.59 and 6.93 ppm),
3. (a) Veselovsky, V. V.; Gybin, A. S.; Lozanova, A. V.; Moiseenkov, A. M.; Smit, W. A.;
Caple, R. Tetrahedron Lett. 1988, 29, 175–178; (b) Sviridova, L. A.; Golubeva, G. A.;
Lescheva, M. F.; Mizgunov, A. V. Khim. Geterosikl. soed. 1995, 1489–1493; (c) Yong,
Z. J.; Yasuda, N.; Furuno, H.; Inanaga, J. Tetrahedron Lett. 2003, 44, 8765–8768.
4. (a) Rooney, J. J.; Pink, R. C. Trans. Faraday Soc. 1962, 58, 1632–1641; (b) Corma, A.;
Garcia, H. Top. Catal. 1998, 6, 127–140; (c) Tanaka, M.; Kobayashi, K. Chem.
Commun. 1998, 1965–1966; (d) Biancardo, M.; Argazzi, R.; Bignozzi, C. A. Inorg.
Chem. 2005, 44, 9619–9621.
5. (a) Sheldrick, G. M. SHELXS-97; University of Go¨ttingen: Germany, 1997; (b)
Sheldrick, G. M. SHELXL-97; University of Go¨ttingen: Germany, 1997.
6. Zefirov, Yu. V. Kristallographia 1999, 44, 1091–1093.
7. Poole, C. P. Electron Spin Resonance. A Comprehensive Treatise on Experimental
Techniques; Wiley-Interscience: New York, NY, 1983.
and pyrrole 4 (6.76 and 7.11 ppm); Ha for pyrrole 5 (6.86 ppm) and
H-atoms of CH2 group for pyrrole 6 (5.70 ppm).
Pyrroles 3–5 used as reference were prepared according to the
procedures reported earlier.1
3.3. The reaction of 2-phenylpyrrole with
bromobenzoylacetylene on ZrO2
A Equimolar amounts of pyrrole (0.143 g, 1 mmol) and bromo-
benzoylacetylene (0.209 g, 1 mmol) were regularly grinded in