Synthesis, crystal structure, and photophysical properties of dimethyl 7-oxa-2a1-azabenzo[b]cyclopenta[pq]pleiadene-1,2-dicarboxylate – novel fused oxazapolycyclic skeleton

Article abstract of DOI:10.1007/s10593-017-2144-3

(Figure Presented.) Dimethyl 3-(2-bromophenyl)dibenzo[b,f]pyrrolo[1,2-d][1, 4]oxazepine-1,2-dicarboxylate and its 3,13b-dihydro and 1,2,3,13b-tetrahydro analogs undergo intramolecular cyclization under free radical conditions with the formation of dimethyl 7-oxa-2a1-azabenzo[b]-cyclopenta[pq]pleiadene-1,2-dicarboxylate, the unique representative of pyrrole-fused dibenzo[b,f][1, 4]oxazepines, consisting of six fused rings. This nonplanar oxazapolyheterocycle shows a strong blue emission in dichloromethane.

Full text of DOI:10.1007/s10593-017-2144-3

DOI 10.1007/s10593-017-2144-3
Chemistry of Heterocyclic Compounds 2017, 53(8), 909–912
Synthesis, crystal structure, and photophysical properties
of dimethyl 7-oxa-2a1-azabenzo[b]cyclopenta[pq]pleiadene-
1,2-dicarboxylate – novel fused oxazapolycyclic skeleton
Petr P. Petrovskii1, Olesya A. Tomashenko1, Mikhail S. Novikov1,
Alexander F. Khlebnikov1*, Helen Stoeckli-Evans2
1 Institute of Chemistry, Saint Petersburg State University,
7/9 Universitetskaya Embankment, Saint Petersburg 199034, Russia;
e-mail: а.khlebnikov@spbu.ru
2 Institute of Physics, University of Neuchâtel,
rue Emile-Argand 11, Neuchâtel CH-2000, Switzerland;
e-mail: helen.stoeckli-evans@unine.ch
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2017, 53(8), 909–912
Submitted May 2, 2017
Accepted June 2, 2017
Dimethyl 3-(2-bromophenyl)dibenzo[b,f]pyrrolo[1,2-d][1,4]oxazepine-1,2-dicarboxylate and its 3,13b-dihydro and 1,2,3,13b-tetrahydro
analogs undergo intramolecular cyclization under free radical conditions with the formation of dimethyl 7-oxa-2a1-azabenzo[b]-
cyclopenta[pq]pleiadene-1,2-dicarboxylate, the unique representative of pyrrole-fused dibenzo[b,f][1,4]oxazepines, consisting of six
fused rings. This nonplanar oxazapolyheterocycle shows a strong blue emission in dichloromethane.
Keywords: oxazaheterocycle, crystal structure, fluorescence, radical arylation.
Recently we developed an approach to several new poly-
heterocyclic frameworks 1–3 with valuable fluorescent pro-
perties1 based on metal-catalyzed cyclizations of o-bromo-
phenyl-substituted hetarylpyrroles (Scheme 1). In these
examples starting pyrroles are formed from strained
2H-azirines and N-phenacylpyridinium or -imidazolium
ylides.1,2 o-Bromophenyl-substituted pyrroles can be also
prepared by cycloaddition of the corresponding azomethine
ylides, generated from aziridines, to acetylenic dipolaro-
philes.
Earlier we performed this reaction with 1-(2-bromo-
phenyl)-1,11b-dihydroazirino[1,2-d]dibenzo[b,f][1,4]oxazepine
(4) and obtained the corresponding pyrroline 5 which was
smoothly dehydrogenated into pyrrole 6 (Scheme 2).3 It is
worth noting that while dibenzo[b,f][1,4]oxazepine scaf-
folds are well known and extensively explored as
pharmaceuticals4 there are only few examples of indole-5
and pyrrole-fused3 dibenzo[b,f][1,4]oxazepines. Polyhetero-
aromatic compounds containing a pyrrole core are very
important in the development of new perspective materials
for bioimaging applications and chemosensor systems.6 We
assumed that compounds 5 and 6 could be good starting
materials for the construction of dimethyl 7-oxa-2a1-
azabenzo[b]cyclopenta[pq]pleiadene-1,2-dicarboxylate (7), a
derivative of a novel fused polyheterocycle, which can also
possess useful photophysical properties.
Scheme 1
Polyheterocycle 7, containing six fused rings was
synthesized through free radical intramolecular C-arylation
0009-3122/17/53(08)-0909©2017 Springer Science+Business Media New York
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Chemistry of Heterocyclic Compounds 2017, 53(8), 909–912
Scheme 2
of three different starting compounds (Scheme 2). It was
found that heating of pyrrole 6 with 1.1 equiv of azabis-
isobutyronitrile (AIBN) in the presence of tributylstannane
in refluxing toluene in 4 h affords compound 7 in 72%
yield. Pyrroline 5, a dihydro derivative of compound 6,
under these conditions also gave compound 7 as the sole
product. It should be noted that even traces of a dihydro
derivative of the cyclization product 7 were not found. This
is in agreement with the fact that pyrroline 5 is easily
oxidized by MnO2 at room temperature (Scheme 2), and
even without added oxidizing agent it undergoes trans-
formation into pyrrole 6 in the presence of air at room
temperature.3 Stereoselective cycloaddition3 of dimethyl
maleate to aziridine 4 led to formation of pyrrolidine 8.
Stereoselectivity of this reaction was discussed in details
earlier.3 Compound 8 is much more resistible to oxidation
in comparison with pyrroline 5. Thus, it requires heating
with MnO2 for several hours to oxidize pyrrolidine 8 into
pyrrole 6. Nevertheless, radical cyclization of pyrrolidine 8
also leads to the formation of pyrrole 7 although it requires
double quantity of AIBN and 7 h of heating in toluene
under reflux. We assume that the arylation takes place
through the usual free radical mechanism.7
Figure 1. Molecular structure of compound 7 with thermal
ellipsoids drawn at the 50% probability level.
The structure of dimethyl 7-oxa-2a1-azabenzo[b]cyclo-
penta[pq]pleiadene-1,2-dicarboxylate (7) was proved by 1H
and 13C NMR, elemental analysis, and mass spectrometry.
Compound 7 is curios and unique example of a fused
polyheterocycle, consisting of six rings. Its structure was
additionally studied by X-ray diffraction analysis (Fig. 1).
Ring C(6)–C(11) lies out of the plane of the rest of the
aromatic system with torsion angle C(5)–O(3)–C(6)–C(11)
being 112.0(1)°.
Figure 2. HOMO (left) and LUMO (right) of compound 7 in
CH2Cl2 (DFT B3LYP/6-31G+(d,p), PCM).
Compound 7 is colorless due to the nonplanar structure
which limits the conjugation of the polycyclic π-system, as
shown also by quantum-chemical calculations using the
time-dependent density functional theory (TD DFT) with
the B3LYP functional and 6-31G+(d,p) basis set (Fig. 2).
The long-wave maximum of absorbance of 340 nm
(ε 9000 M–1·cm–1) in dichloromethane is close to the
calculated value (350 nm), solvent effects being accounted
for by the polarized continuum model (PCM) for dichloro-
methane as the solvent.8 Compound 7 shows a strong blue
emission around 418 nm in dichloromethane with the
absolute quantum yield about 18%. The spectra of absorp-
tion, excitation, and emission spectra are given in Figure 3.
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Chemistry of Heterocyclic Compounds 2017, 53(8), 909–912
a mixture of CH2Cl2 and MeOH to obtain product 8. Yield
127 mg (91%), colorless solid, mp 234–235°C. IR spectrum
(CHCl3), ν, cm−1: 3068, 2956, 2860, 1746, 1604, 1498,
1458, 1440, 1322, 1264, 1052. 1Н NMR spectrum (300 MHz,
CDCl3), δ, ppm (J, Hz): 3.48 (1H, dd, J = 6.9, J = 0.4,
CHCO2CH3); 3.73 (3H, s, CO2CH3); 3.75 (1H, dd, J = 11.0,
J = 7.4, CHCO2CH3); 3.83 (3H, s, CO2CH3); 5.35 (1H, d,
J = 0.4, CHN); 5.97 (1H, dd, J = 7.4, J = 2.2, CHN); 6.34
(1H, d, J = 11.0, H Ar); 6.60–6.66 (1H, m, H Ar); 6.75–
6.81 (1H, m, H Ar); 6.97 (1H, dd, J = 7.4, J = 2.2, H Ar);
7.16–7.41 (7H, m, H Ar); 7.64 (1H, dd, J = 7.4, J =2.2, H Ar).
13С NMR spectrum (75 MHz, CDCl3), δ, ppm: 45.3; 51.9;
52.4; 52.7; 58.9; 67.2; 115.7; 118.1; 120.9; 121.7; 122.2;
123.8; 125.0; 125.2; 127.9; 128.1; 129.4; 129.8; 131.2;
133.5; 137.5; 139.3; 144.2; 158.4; 170.0; 171.4. Found, %:
C 61.64; H 4.55; N 2.61. C26H22BrNO5. Calculated, %:
C 61.43; H 4.36; N 2.76.
Dimethyl 7-oxa-2a1-azabenzo[b]cyclopenta[pq]pleiadene-
1,2-dicarboxylate (7). Method I. Solution of (3SR,13bRS)-3-
(2-bromophenyl)-3,13b-dihydrodibenzo[b,f]pyrrolo[1,2-d]-
[1,4]oxazepine-1,2-dicarboxylate (5) (100 mg, 0.235 mmol) or
dimethyl 3-(2-bromophenyl)dibenzo[b,f]pyrrolo[1,2-d][1,4]-
oxazepine-1,2-dicarboxylate (6) (100 mg, 0.236 mmol),
AIBN (41 mg, 0.25 mmol, 1.1 equiv), and Bu3SnH (32 mg,
0.11 mmol, 0.5 equiv) in toluene (5 ml) was heated at 80°C
for 4 h. Then toluene was evaporated under reduced pres-
sure, and the residue was purified by column chromato-
graphy on silica gel (hexane–AcOEt, 7:1).
Figure 3. Room temperature absorption, excitation, and emission
spectra of compound 7 in CH2Cl2 (c 7·10–6 M).
In conclusion, o-bromophenyl-substituted pyrroles appear to
be versatile building blocks which allow obtaining fused
pyrrole-containing polyheterocyclic frameworks through
free radical cyclization. A novel hexacyclic ortho- and peri-
fused polyheterocycle shows a strong blue emission with
high quantum yield despite non-planarity.
Experimental
Method II. Solution of dimethyl (1RS,2SR,3SR,13bRS)-
3-(2-bromophenyl)-1,2,3,13b-tetrahydrodibenzo[b,f]pyrrolo-
[1,2-d][1,4]oxazepine-1,2-dicarboxylate (8) (100 mg,
0.234 mmol), AIBN (41 mg, 0.248 mmol, 1.1 equiv), and
Bu3SnH (32 mg, 0.109 mmol, 0.5 equiv) in toluene (5 ml)
was heated at 80°C for 4 h. As the reaction wasn't complete,
AIBN (41 mg, 0.248 mmol, 1.1 equiv) was added and the
reaction mixture was heated at 80°C for additional 3 h.
Then toluene was removed under reduced pressure, and the
residue was purified by column chromatography on silica
gel (hexane–AcOEt, 7:1). Yield 67 mg (68%, method I,
from compound 5), 71 mg (72%, method I, from compound
6), 56 mg (56%, method II), colorless solid, mp 277–278°C.
IR spectrum (KBr), ν, cm−1: 3064, 2949, 1728, 1698, 1527,
1436, 1210, 749. UV spectrum (CH2Cl2), λmax(log ε): 340 (4).
1Н NMR (400 MHz, CDCl3), δ, ppm (J, Hz): 3.86 (3H, s,
CO2CH3); 4.06 (3H, s, CO2CH3); 7.17–7.24 (1H, m, H Ar);
7.35–7.57 (7H, m, H Ar); 8.13 (1H, dd, J = 7.5, J = 2.0,
H Ar); 8.23–8.28 (1H, m, H Ar); 8.30–8.36 (1H, m, H Ar).
13С NMR spectrum (75 MHz, CDCl3), δ, ppm: 52.1; 52.8;
112.8; 117.2; 119.9; 120.4; 121.3; 122.8; 123.6; 124.3;
124.4; 125.0; 125.8; 125.9; 126.5; 126.8; 128.1; 128.5; 128.9;
130.8; 131.2; 132.8; 149.9; 157.0; 165.1; 167.6. Found, m/z:
424.1196 [M+H]+. C26H18NO5. Calculated, m/z: 424.1180.
Found, %: C 73.84; H 4.12; N 3.27. С26H17NO5. Calculated,
%: C 73.75; H 4.05; N 3.31.
IR spectra were recorded on a Specord M80 spectro-
meter. UV/Vis spectra were recorded on a Shimadzu
UV-1800 spectrophotometer. The emission and excitation
spectra in solution were recorded on a JY Horiba Fluorolog-3
spectrofluorimeter. 1H (300 and 400 MHz) and 13C
(75 MHz) NMR spectra were recorded on Bruker DPX 300
and Bruker Avance 400 instruments CDCl3. The solvent
1
peak (δ 7.26 ppm for H nuclei, 77.0 ppm for 13C nuclei)
was used as chemical shift reference. High-resolution mass
spectra were recorded on a Bruker maXis HRMS-ESI-
QTOF, electrospray ionization, positive mode. Elemental
analysis was performed on a EuroEA3000 CHN-analyzer.
Melting points were determined on melting point apparatus
Stuart SMP 30. Thin-layer chromatography (TLC) was
conducted on silica gel (Macherey-Nagel, 0.2 mm on alu-
minum sheets, fluorescent indicator). All the photophysical
measurements in solution were carried out in freshly
distilled dry CH2Cl2 (c 7·10–6 M). Direct quantum yield
measurements of the samples were performed at room
temperature with a Horiba Quanta-phi integrating sphere.
Compounds 4–6 were obtained according to literature
procedures.9
Dimethyl (1RS,2SR,3SR,13bRS)-3-(2-bromophenyl)-
1,2,3,13b-tetrahydrodibenzo[b,f]pyrrolo[1,2-d][1,4]ox-
azepine-1,2-dicarboxylate (8). Dimethyl maleate (51 mg,
0.35 mmol, 1.3 equiv) was added to a stirred solution of
(1RS,11bRS)-1-(2-bromophenyl)-1,11b-dihydroazirino[1,2-d]-
dibenzo[b,f][1,4]oxazepine (4) (100 mg, 0.275 mmol) in
dry toluene (5 mml). The reaction mixture was refluxed for
8 h. Then the volatiles were evaporated under reduced
pressure. The residue was purified by recrystallization from
X-ray structural study of compound 7. Suitable
crystals of compound 7 were obtained as colorless rods by
slow evaporation of a solution in hexane – ethyl acetate.
The intensity data were collected at 173 K (–100°C) on a
Stoe Mark II-Image Plate Diffraction System10 equipped
911

Chemistry of Heterocyclic Compounds 2017, 53(8), 909–912
Ingravallo, P.; Asante-Appiah, E.; Nomeir, A.; Fells, J.;
with a two-circle goniometer and using MoKα graphite
monochromated radiation. The structure was solved by
direct methods with SHELXS.11 The structure refinement
and all further calculations were carried out with SHELXL-
2016.12 The H atoms were included in calculated positions
and treated as riding atoms using SHELXL-2016 default
parameters. The non-hydrogen atoms were refined aniso-
tropically, using weighted full-matrix least squares on F2.
Figure 1 was drawn using the PLATON software.13 The
complete crystallographic data set was deposited at the
Cambridge Crystallographic Data Center (deposit CCDC
1546899).
Kozlowski, J. A. Bioorg. Med. Chem. Lett. 2016, 26, 3158.
5. (a) Hu, F.; Liu, H.; Jia, J.; Ma, C. Org. Biomol. Chem. 2016,
14, 11076. (b) Sang, P.; Yu, M.; Tu, H.; Zou, J.; Zhang, Y.
Chem. Commun. 2013, 701.
6. (a) Grzybowski, M.; Glodkowska-Mrowka, E.; Clermont, G.;
Blanchard-Desce, M.; Gryko, D. T. Chem. Heterocycl.
Compd. 2017, 53, 72. [Khim. Geterotsikl. Soedin. 2017, 53,
72.] (b) Santra, M.; Jun, Y. W.; Bae, J.; Sarkar, S.; Choi, W.;
Gryko, D. T.; Ahn, K. H. Asian J. Org. Chem. 2017, 6, 278.
(c) Ge, Y.; Liu, A.; Dong, J.; Duan, G.; Cao, X.; Li, F. Sens.
Actuators, B 2017, 247, 46. (d) Łukasiewicz, Ł. G.;
Deperasińska, I.; Poronik, Y. M.; Jun, Y. W.; Banasiewicz, M.;
Kozankiewicz, B.; Ahn, K. H.; Gryko, D. T. Chem.–Asian J.
2016, 11, 1718. (e) Yu, C.; Wu, Q.; Wang, J.; Wei, Y.; Hao, E.;
Jiao, L. J. Org. Chem. 2016, 81, 3761. (f) Sareen, D.; Lee, J. H.;
Hwang, H.; Yoo, S.; Lee, C.-H. Chem. Commun. 2016, 52,
5852. (g) Koshel, E. I.; Tomashenko, O. A.; Khlebnikov, A. F.;
Gaginskaya, E. R.; Saifitdinova, A. F.; Tunik, S. P.
Chromosome Res. 2016, 24 (Suppl 1), 29. DOI: 10.1007/
s10577-016-9532-x
We gratefully acknowledge the financial support of the
Russian Science Foundation (grant No. 16-13-10036). This
research was carried out using resources of the Center for
Magnetic Resonance, the Computer Center, and the Center
for Chemical Analysis and Materials, the Center for
Optical and Laser Materials Research of Saint Petersburg
State University.
7. Togo, H. Advanced Free Radical Reactions for Organic
Synthesis; Elsevier: Amsterdam, 2004, p. 1.
References
8. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.;
Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.;
Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.;
Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.;
Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.;
Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.;
Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.;
Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.;
Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.;
Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09. Revision
D.01; Gaussian, Inc.: Wallingford, 2009.
1. (a) Tomashenko, O. A.; Khlebnikov, A. F.; Mosiagin, I. P.;
Novikov, M. S.; Grachova, E. V.; Shakirova, J. R.; Tunik, S. P.
RCS Adv. 2015, 5, 94551. (b) Tomashenko, O. A.; Novikov, M. S.;
Khlebnikov, A. F. J. Org. Chem. 2017, 82, 616.
2. (a) Khlebnikov, A. F.; Golovkina, M. V.; Novikov, M. S.;
Yufit, D. S. Org. Lett. 2012, 14, 3768. (b) Khlebnikov, A. F.;
Tomashenko, O. A.; Funt, L. D.; Novikov, M. S. Org.
Biomol. Chem. 2014, 12, 6598.
3. Khlebnikov, A. F.; Novikov, M. S.; Petrovskii, P. P.;
Konev, A. S.; Yufit, D. S.; Selivanov, S. I.; Frauendorf, H.
J. Org. Chem. 2010, 75, 5211.
4. (a) Gijsen, H. J. M.; Berthelot, D.; Zaja, M.; Brône, B.;
Geuens, I.; Mercken, M. J. Med. Chem. 2010, 53, 7011.
(b) Binaschi, M.; Boldetti, A.; Gianni, M.; Maggi, C. A.;
Gensini, M.; Bigioni, M.; Parlani, M.; Giolitti, A.; Fratelli, M.;
Valli, C.; Terao, M.; Garattini, E. ACS Med. Chem. Lett.
2010, 1, 411. (c) Deraeve, C.; Guo, Z.; Bon, R. S.;
Blankenfeldt, W.; Di Lucrezia, R.; Wolf, A.; Menninger, S.;
Stigter, E. A.; Wetzel, S.; Choidas, A.; Alexandrov, K.;
Waldmann, H.; Goody, R. S.; Wu, Y.-W. J. Am. Chem. Soc.
2012, 134, 7384. (d) Chen, C.-L.; Lee, C.-C.; Liu, F.-L.;
Chen, T.-C.; Ahmed Ali, A. A.; Chang, D.-M.; Huang, H.-S.
Eur. J. Med. Chem. 2016, 117, 70. (e) Yu, W.; Coburn, C. A.;
Yang, D.-Y.; Meinke, P. T.; Wong, M.; Rosenblum, S. B.;
Chen, K. X.; Njoroge, G. F.; Chen, L.; Dwyer, M. P.; Jiang, Y.;
Nair, A. G.; Selyutin, O.; Tong, L.; Zeng, Q.; Zhong, B.; Ji, T.;
Hu, B.; Agrawal, S.; Xia, E.; Zhai, Y.; Liu, R.; Kong, R.;
9. Khlebnikov, A. F.; Novikov, M. S.; Petrovskii, P. P.; Magull, J.;
Ringe, A. Org. Lett. 2009, 11, 979.
10. X-Area & X-RED32 Software; Stoe & Cie GmbH: Darmstadt,
2016.
11. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2008, A64, 112.
12. Sheldrick, G. M. Acta Crystallogr., Sect. C: Struct. Chem.
2015, C71, 3.
13. Spek, A. L. Acta Crystallogr., Sect. D: Biol. Crystallogr.
2009, D65, 148.
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