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Synthesis of carbazole derived aza[7]helicenes
Tetrahedron Letters 55 (2014) 5394–5399
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Synthesis of carbazole derived aza[7]helicenes Gourav M. Upadhyay a, , Harish R. Talele a, , Sibaprasad Sahoo b, Ashutosh V. Bedekar a,⇑ a b
Department of Chemistry, Faculty of Science, M. S. University of Baroda, Vadodara 390 002, India Sun Pharma Advanced Research Centre, Tandalja, Vadodara 390 020, India
a r t i c l e
i n f o
Article history: Received 24 June 2014 Revised 27 July 2014 Accepted 28 July 2014 Available online 2 August 2014 Keywords: Aza[7]helicene Photocyclization Carbazole Mizoroki–Heck coupling One-pot Wittig–Heck reaction
a b s t r a c t Synthesis of four derivatives of symmetrical aza[7]helicenes is achieved by I2-THF mediated photocyclization of corresponding bis-styryl derivatives. The cyclization furnished the desired angularly fused azahelicene in moderate yields. The structures are established by NMR spectroscopy and single crystal X-ray analysis for the difluoro derivative. The series of synthesized aza[7]helicenes showed remarkable thermal stability as indicated by DSC analysis. Ó 2014 Elsevier Ltd. All rights reserved.
Molecules possessing ortho-fused aromatic rings, acquire a unique shape in order to release the internal strain. This type of molecular arrangement acquires helical structure and shows stereoisomerism. The helical molecules have attracted much attention in recent years due to some unique properties associated with their structure.1 The efficient delocalization of p-electrons and non-planarity of the structure in helicenes enable them to be stable to strong acids and high temperature. Applications of helical molecules cover a wide range in fields of material science,2 asymmetric synthesis and catalysis,3 as molecular motor,4 in biology5 etc. A number of approaches have been developed for the synthesis of these screw shaped molecules due to efforts required to overcome the inherent steric factors or steric crowding. Therefore, the synthesis of new helical molecules remains an exciting challenge and a rewarding endeavor. Helical or helicene like molecules possessing heteroatoms are of considerable interest due to the additional properties. Although considerable attention has been devoted to the thia-helicenes,6 the aza-helicenes, containing one or more nitrogen atom, have also gained interests.7 Most of these aza-helicenes or aza-helicene like compounds are derivatives of pyridine, but only a few analogues of pyrrole (pyrrolohelicenes) are studied. The first example, pyrrolo[5]helicene I (Fig. 1), was reported by Meisenheimer and Witte,8 way back in early 20th century, which was followed by a report on the synthesis of pyrrolo[6]helicene II by Fuchs and Niszel.9a
NH
NH
HN
N CH 6 13
N C6H13 I (Meisenheimer 1903)
II (Fuchs 1927)
III (Liu 2012)
Br
N R
NPh IV (Nozaki 2005)
N Me V (Hassine 2013)
N R
VI (List 2014)
Figure 1. Known carbazole-based azahelicenes.
R'' R''
R'' R''
N
N
R' aza[7]helicene
R'
Figure 2. Retrosynthetic scheme for aza[7]helicene
⇑ Corresponding author. Tel.: +91 265 2795552.
E-mail address: [email protected] (A.V. Bedekar). These authors contribute equally.
http://dx.doi.org/10.1016/j.tetlet.2014.07.116 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Later the same type of compound was synthesized and resolved by Pischel et al.9b Lately another derivative III was synthesized
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I
R''
R''
I
R'' R''
N H
N R'
1
hu I2-THF
2, R' = n-Bu
R''
R'' R'' 3, R'' = H; 4, R'' = Me 2
Toluene 24 h
N
N
R'
R'
5, R' = n-Bu; R'' = H 6, R'= n-Bu; R'' = Me 9, R' = n-Bu; R'' = OMe 12, R' = n-Bu; R'' = F
13, R' = n-Bu; R'' = H (44 %) 14, R' = n-Bu; R'' = Me (40 %) 15, R' = n-Bu; R'' = OMe (44 %) 16, R' = n-Bu; R'' = F (37 %)
Scheme 3. Photocyclization of distyryl carbazoles.
Pd(OAc)2 - dppp K2CO3
N
140 oC, 48 h
R' 5, R' = n-Bu, R'' = H (94 %) 6, R' = n-Bu, R'' = Me (87 %)
Scheme 1. Synthesis of (E,E) 3,6-distyryl-9-butyl-9H-carbazoles by Mizoroki–Heck reaction.
and investigated as deep-blue-emitting OLED by Liu et al.10 This particular diaza[7]helicene consists of two linear and angularly cyclized units of carbazole moiety. However, the angularly cyclized aza[7]helicene IV has been previously reported by Nozaki.11 The synthesis was independently reported by Pd catalyzed coupling reactions. Another pyrrolo[5]helicene V system was recently prepared by Hassine et al.12 which consisted of an unsymmetric unit of carbazole. Very recently List and co-workers13 have efficiently synthesized bis-azahelicene VI, along with other derivatives with an elegant use of organocatalysts for double Fischer indolizationoxidation protocol. The synthesis has also been extended to asymmetric version by using chiral phosphoric acid catalyst. Considering the large interest in the field of helical molecules these form a small group of examples of pyrrole based heterohelicenes and the area still remains scarcely explored. In continuation of our work on photocyclization14 and helicenelike molecules,15,16 this Letter presents the synthesis of symmetrical aza[7]helicenes. The retrosynthetic plan to access these molecules indicates the possible option of oxidative double photocyclization of stilbene type analogues of carbazole (Fig. 2). The required starting material for the photoreaction can be easily prepared by Mizoroki–Heck reaction of 3,6-diiodo-9-alkyl-9H-carbazole with appropriate styrene. By choosing a suitable styrene, different functional groups can be introduced on aza[7]helicenes and can be a general preparative method. The earlier synthesis of similar aza[7]helicene was performed by different methods of cyclization.11
The required starting material 3,6-diiodo-9-butyl-9H-carbazole 2 was prepared from carbazole 1 by known procedures.17 To increase the solubility of resultant aza[7]helicene the n-Bu group was selected.18 It was then subjected to double Mizoroki–Heck reaction in the presence of palladium catalyst, dppp, K2CO3, and styrene 3, in order to obtain corresponding (E,E)-3,6-distyryl-9butyl-9H-carbazole 5 in excellent yields.19 A similar scheme with 4-methyl styrene 4 was followed to prepare the corresponding dimethyl derivative 6 (Scheme 1). However, this option has the limitation of the availability of the required styrene derivative for the Mizoroki–Heck reaction. Some substituted styrenes are not readily available or are unstable, hence to overcome this problem we have recently developed a protocol of making them in situ for a one-pot reaction.20 In this process an aldehyde with required substituent was subjected to the Wittig reaction with a one carbon phosphonium salt (Ph3PCH3I) to generate the desired styrene derivative, which was further subjected to Mizoroki–Heck condition in the same flask to give the stilbene derivative. This new methodology is advantageous due to the availability of substituted aldehydes which can compensate for the poor accessibility of certain styrenes. This process was also applied for the synthesis of two more derivatives of the present distyryl carbazoles. In this way a method can be developed to prepare any type of (E,E)-3,6-distyryl-9-alkyl-9H-carbazole required for the synthesis of aza[7]helicene. In the present work two derivatives from 4-methoxy benzaldehyde 7 and 4-fluoro benzaldehyde 10 are utilized to prepare 4-methoxy styrene 8 and 4-fluoro styrene 11, respectively, which were in situ subjected to one-pot Mizoroki–Heck reaction with 2 (Scheme 2). The distyryl derivative of carbazole 5 obtained was subjected to photocyclization in toluene with the high pressure mercury vapor lamp. The reaction was carried out in the presence of stoichiometric amount of iodine as an oxidizing agent and THF as a scavenger of the hydrogen iodide formed.14 Careful analysis of the reaction mixture revealed consumption of the starting material and forma-
R''
R''
CHO
R''
Ph3PCH3I
2
K2CO3
Pd(OAc)2 - dppp K2CO3 140 oC, 48 h
R''
7, R'' = OMe 10, R'' = F
8, R'' = OMe 11, R'' = F
N R' 9, R' = n-Bu; R'' = OMe (87 %) 12, R' = n-Bu; R'' = F (52 %)
Scheme 2. Synthesis of (E,E) 3,6-distyryl-9-butyl-9H-carbazoles by one-pot Wittig–Heck reaction.
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Figure 3. ORTEP plot of 16.
Table 1 Select X-ray crystallographic data of the compound 1621
a
Inner carbon–carbon bond lengths (Å) C17c–C17d C17d–C17e C17e–C17f C1–C17f
1.455 1.424 1.440 1.403
Distance between non bonded atoms (°) F22–F23 C3–C15 C2–C16 C1–C17
5.432 4.446 3.913 3.003
Outer carbon–carbon bond length (Å) C3–C4 C5–C6 C7–C8
1.358 1.332 1.342
C17a–C17f C17b–C17e C11–C12 C13–C14
3.529 3.559 2.444 2.454
Torsion angle (°) u 1 = C17–C17a–C17b–C17c u 2 = C17a–C17b–C17c–C17d u 3 = C17b–C17c–C17d–C17e
14.83 17.03 17.27
Distortion of the molecular structure (°) u 1+u 2+u 3
49.13
Dihedral angle h (°)a
35.84
Angle between planes passing through C1–C2–C3–C4–C4a–C17f and C13a–C14–C15–C16–C17–C17a rings.
tion of a major product, which was isolated by column chromatography over silica gel. The 1H NMR analysis of 13 clearly established the double angular cyclization (Scheme 3). Photocyclization was also extended to other three derivatives 6, 9, and 12 to afford similarly cyclized aza[7]helicenes 14, 15, and 16 respectively in moderate yields. In all the cases the double angularly fused systems were isolated and characterized by 1H NMR analysis and supported by other spectral techniques. The hydrogen attached to C4 (& C5) of 5 appeared at 8.3 d as a singlet disappeared in 13 on cyclization. This is a clear evidence of angular cyclization. In compound 13 the inside protons attached to C2 (& C16) appeared most upfield in the aromatic region at 6.21-6.28 d, followed by signal at 7.16-7.20 d for
Table 2 Prominent UV–vis bands of 13–16 Compound
Figure 4. UV–visible spectra of aza[7]helicenes.
13 14 15 16
Wavelength (nm) 260 261 260 257
326 326 318 315
335 333 330 327
385 388 394 390
401 404 414 408
G. M. Upadhyay et al. / Tetrahedron Letters 55 (2014) 5394–5399
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Figure 5. DSC thermogram of aza[7]helicenes 13 to 16.
Table 3 Thermal behavior of 13–16 by DSC analysis Compound
Melting point (°C)
Glass Transition Temperature Tg (°C)
13 14 15 16
208.9 246.0 200.5 210.7
151.0 197.3 147.5 173.1
the protons attached to C3 (& C15). The other two protons attached to C1 (& C17) and C4 (& C14) of the terminal rings appeared at 7.43–7.45 and 7.81–7.83 d. All the four aza[7]helicenes are quite soluble in organic solvents such as toluene, dichloromethane, chloroform, acetone, and ethyl acetate. A pale yellow crystal of 16 was obtained from ethyl acetate-hexane and analyzed by single crystal X-ray diffraction (Fig. 3).21 Select bond lengths, distances of non-bonded atoms, and torsion angles are presented in Table 1. Some of the bonds of the outer side C3–C4, C5–C6, and C7–C8 were of the order of 1.332–1.358 Å, much shorter compared to the average bond of benzene (1.39 Å). For helicene structure, as expected the inside bond lengths were found to be elongated in the range of 1.403– 1.455 Å. The distance between the non-bonded atoms of the last two terminal rings of this compound clearly indicated that they were separated by about 4 Å. The two carbon atoms bearing fluorine (C2–C16) were seen to be separated by 3.913 Å and the fluorine atom was located almost beneath the last aromatic ring of aza[7]helicene structure. The distance between C11-C12 and C13-C14 was in the range of 2.444-2.454 Å which is shorter than the corresponding C1-C10 of phenanthrene (2.473 Å). This marginal decrease was due to the helical shape of the molecule and contributed in the upfield shift in the 19F NMR spectra. This could be due to the shielding effect of the ring. The torsion angle along the inner frame of aza[7]helicene varied from 14.83 to 17.27, a characteristic measure of helicity. The sum of the three dihedral angles u 1, u 2, and u 3 was observed to be 49.13°, which is considered to be quite pronounced and may offer good rigidity to isomers. The analysis of 16 on chiral phase HPLC supported this observation where the two well separated peaks for the helical isomers were detected [Chiralcel OD-H; IPA in hexane (10%), 1.0 mL/ min, 6.5 and 8.3 min].
The aza[7]helicene derivatives were investigated using UV–vis absorption study performed in methanolic solution (5.0 10 5 mol). Spectra of these compounds exhibited a strong absorption in the region of 257–414 nm (Fig. 4). The analysis was in accordance with the expected values and several significant absorption bands were observed (Table 2). Thermal behavior of aza[7]helicenes was investigated by means of differential scanning calorimetry (DSC) where the sample was heated at the rate if 10 °C/min from 25 to 300 °C, under the inert atmosphere of nitrogen (Fig. 5). The analysis indicated the melting point of compounds to be in the range of 200–246 °C. The glass transition temperatures (Tg) of aza[7]helicenes lie in 147–197 °C (Table 3), which point toward high thermal stability of the helical system. It is noteworthy to observe higher values of Tg for the present aza[7]helicenes as compared to the earlier reported aza[5]helicene.12 In summary an efficient method has been developed for preparing aza[7]helicene by double angular photocyclization of distyryl carbazoles.22 Products are well characterized to establish the structure and the associated helicity. The series of aza[7]helicenes synthesized showed remarkable thermal stability as measured by DSC analysis. Acknowledgments We wish to thank the Science and Engineering Research Board (SERB), New Delhi for the financial assistance for this work [No. SR/S1/OC-74/2012]. We also thank the Department of Science and Technology (DST), New Delhi for the PURSE project under which the X-Ray Diffraction Machine was acquired in the Faculty of Science. References and notes 1. (a) Grimme, S.; Harren, J.; Sobanski, A.; Vögtle, F. Eur. J. Org. Chem. 1998, 1491– 1509; (b) Urbano, A. Angew. Chem., Int. Ed. 2003, 42, 3986–3989; (c) Collins, S. K.; Vachon, M. P. Org. Biomol. Chem. 2006, 4, 2518–2524; (d) Rajca, A.; Miyasaki, M. In Functional Organic Materials; Muller, T. J. J., Bunz, U. H. F., Eds.; WileyVCH: Weinheim, 2007; pp 547–581; (e) Shen, Y.; Chen, C.-F. Chem. Rev. 2012, 112, 1463–1535; (f) Gingras, M. Chem. Soc. Rev. 2013, 42, 968–1006; (g) Gingras, M.; Félix, G.; Peresutti, R. Chem. Soc. Rev. 2013, 42, 1007–1050; (h) Gingras, M. Chem. Soc. Rev. 2013, 42, 1051–1095.
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Kötzner, L.; Webber, M. J.; Martínez, A.; De Fusco, C.; List, B. Angew. Chem., Int. Ed. 2014, 53, 5205. 14. Talele, H. R.; Gohil, M. J.; Bedekar, A. V. Bull. Chem. Soc. Jpn. 2009, 82, 1182– 1186. 15. (a) Talele, H. R.; Sahoo, S.; Bedekar, A. V. Org. Lett. 2012, 14, 3166–3169; (b) Talele, H. R.; Bedekar, A. V. Org. Biomol. Chem. 2012, 10, 8579–8582. 16. Shyam Sundar, M.; Talele, H. R.; Mande, H. M.; Bedekar, A. V.; Tovar, R. C.; Muller, G. Tetrahedron Lett. 2014, 55, 1760–1764. 17. (a) Chuang, C.-N.; Chuang, H.-J.; Wang, Y.-X.; Chen, S.-H.; Huang, J.-J.; Leung, M.-K.; Hsieh, K.-H. Polymer 2012, 53, 4983–4992; (b) Liu, X.; Sun, Y.; Zhang, Y.; Zhao, N.; Zhao, H.; Wang, G.; Yu, X.; Liu, H. J. Fluoresc. 2011, 21, 497–506. 18. Zhao, T.; Liu, Z.; Song, Y.; Xu, W.; Zhang, D.; Zhu, D. J. Org. Chem. 2006, 71, 7422–7432. 19. Carbi, W.; Candiani, I.; Bedeschi, A.; Penco, S.; Santi, R. J. Org. Chem. 1992, 57, 1481–1486. 20. (a) Saiyed, A. S.; Bedekar, A. V. Tetrahedron Lett. 2010, 51, 6227–6231; (b) Bedekar, A. V.; Chaudhary, A. R.; Shyam Sundar, M.; Rajappa, M. Tetrahedron Lett. 2013, 54, 392–396. 21. Crystallographic data for the structures of compound 16 has been deposited with the Cambridge Crystallographic Data Centre (CCDC No. 1004161). Copies of the data can be obtained from http://www.ccdc.cam.ac.uk/conts/ retrieving.html or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CD21EZ, UK (fax: +44-1223-336-033; e-mail: [email protected]). Atom numbers in Figure 3 are assigned based on IUPAC rules and are different from the pattern in ORTEP data submitted to CCDC. 22. Synthesis of 3,6-distyryl-9-butyl-9H-carbazole (5) by Mizoroki–Heck reaction: A solution of palladium acetate (0.009 g, 0.042 mmol, 2 mol %) and 1,3bis(diphenylphosphinopropane) (0.034 g, 0.084 mmol, 4 mol %) was prepared in N,N-dimethylacetamide (5 mL) under nitrogen atmosphere. The mixture was stirred at room temperature until a homogeneous solution was obtained. This catalyst solution was repeatedly purged by N2 prior to use. A two-necked round bottom flask was charged with 3,6-diiodo-Nbutylcarbazole (1.0 g, 2.1 mmol), dry potassium carbonate (1.16 g, 8.4 mmol),
TBAB (0.135 g, 0.42 mmol, 20 mol %), and N,N-dimethylacetamide (10 mL). The solution was repeatedly purged with N2. Styrene (0.546 g, 5.25 mmol) was added at 60 °C and the mixture was heated up to 100 °C. At 100 °C, the previously prepared Pd catalyst solution was added dropwise and the mixture was further heated to 140 °C for 48 h. After the completion of the reaction, the mixture was poured into ice-cold water and extracted with dichloromethane (3 x 100 mL). The combined organic phase was washed with water, brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel using petroleum ether–ethyl acetate (98:2) as eluent to afford predominantly trans isomer of 3,6-distyryl-N-butylcarbazole. 0.845 g (94%); mp 152–156 °C. 1 H NMR (400 MHz, CDCl3): d 8.30 (s, 2H), 7.72–7.69 (dd, J = 8.8, 1.6 Hz, 2H), 7.63–7.61 (d, J = 7.6 Hz, 4H), 7.45–7.28 (m, 9H), 7.23–7.19 (d, J = 16.4 Hz), 4.32–4.28 (t, J = 7.2, 2H), 1.91–1.85 (q, 2H), 1.48–1.40 (m, 2H), 1.01–0.97 (t, J = 7.2 Hz, 3H). MS (EI): m/z, (%) 428 (83), 427 (24), 426 (100), 385 (55). IR (KBr): t 3438, 3023, 2954, 2867, 1725, 1623, 1592, 1484, 1382, 1341, 1244, 1208, 1153, 1130, 1070, 959, 881, 802, 751, 690 cm 1. Synthesis of 3,6-di(4-methoxystyryl)-9-butyl-9H-carbazole (9) by one-pot Wittig– Heck reaction: A solution of palladium acetate (0.010 g, 0.042 mmol, 2 mol %) and 1,3bis(diphenylphosphinopropane) (0.034 g, 0.084 mmol, 4 mol %) was prepared in N,N-dimethylacetamide (5 mL) under nitrogen atmosphere. The mixture was stirred at room temperature until a homogeneous solution was obtained. This catalyst solution was repeatedly purged by N2 prior to use. A two-necked round bottom flask was charged with 3,6-diiodo-Nbutylcarbazole (1.0 g, 2.10 mmol), 4-methoxy benzaldehyde 7 (0.715 g, 5.26 mmol), methyltriphenylphosphonium iodide (2.56 g, 6.31 mmol), dry potassium carbonate (2.18 g, 15.7 mmol), TBAB (0.135 g, 0.42 mmol, 20 mol %), and N,N-dimethylacetamide (10 mL) and the mixture was heated up to 100 °C. At 100 °C, the previously prepared Pd catalyst solution was added dropwise and the mixture was heated to 140 °C for 48 h. After the completion of the reaction similar work-up procedure was followed as discussed above. Pure product was isolated by column chromatography on silica gel using petroleum ether–ethyl acetate (95:5) as eluent to afford predominantly trans isomer of 3,6-bis-(4-methoxystyryl)-N-butylcarbazole; 0.887 g (87%); mp 201– 203 °C. 1 H NMR (400 MHz, CDCl3): d 8.22–8.21 (d, J = 1.2 Hz, 2H), 7.63–7.61 (dd, J = 8.4, 1.2 Hz, 2H), 7.51–7.48 (d, J = 8.8 Hz, 4H), 7.34–7.32 (d, J = 8.4 Hz, 2H), 7.20– 7.16 (d, J = 16.4 Hz), 7.12–7.08 (d, J = 16.4 Hz, 2H), 6.93–6.91 (broad d, 4H), 4.27–4.23 (t, J = 7.2, 2H), 3.83 (s, 6H), 1.87–1.80 (m, 2H), 1.42–1.33 (m, 2H), 0.98–0.91 (t, J = 7.2 Hz, 3H). MS (EI): m/z, (%) 489 (10), 488 (29), 487 (100), 486 (42), 485 (47), 445 (10), 444 (13), 443 (16), 428 (08), 341 (06), 243 (10), 136 (12), 95 (16). IR (KBr): t 3429, 3020, 2957, 1872, 1604, 1482, 1383, 1344, 1301, 1246, 1175, 1109, 1033, 961, 851, 818, 760 cm 1. General procedure for photocyclodehydrogenation:14 Synthesis of N-butylaza[7]helicene (13): A solution of 3,6-distyryl-N-butylcarbazole 5 (0.350 g, 0.82 mmol), iodine (0.457 g, 1.80 mmol), dry THF (2.95 g, 3.32 mL, 41.3 mmol), and toluene (1.2 L) was irradiated using a 125 W HMPV lamp (24 h monitored by tlc). After the completion of the reaction, the excess of iodine was removed by washing the solution with aqueous Na2S2O3 and water. The organic layer was concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography over silica gel using petroleum ether– ethyl acetate (98:2) as eluent to obtain a pale yellow solid. 0.151 g (44%); mp 214–215 °C. 1 H NMR (400 MHz, CDCl3): d 8.13–8.11 (d, J = 8.4 Hz, 2H), 8.03–8.01 (d, J = 8.4 Hz, 2H), 7.97–7.95 (d, J = 8.4 Hz, 2H), 7.84–7.82 (d, J = 8.8 Hz, 2H), 7.83–7.81 (d, J = 7.6 Hz, 2H), 7.45–7.43 (d, J = 8.4 Hz, 2H), 7.20–7.16 (ddd, J = 8.0, 6.8, 1.2 Hz, 2H), 6.26–6.21 (ddd, J = 8.4, 6.8, 1.2 Hz, 2H), 4.79–4.75 (t, J = 7.2 Hz, 2H), 2.13–2.04 (m, 2H), 1.59–1.49 (m, 2H), 1.04–1.00 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 139.32, 131.29, 130.23, 128.25, 127.09, 126.75, 126.69, 126.61, 126.22, 125.92, 124.25, 122.63, 116.75, 109.62, 43.43, 31.93, 20.71, 13.99. MS (EI): m/z, (%) 423 (100), 380 (34), 379 (15), 378 (04), 377 (06), 366 (13), 364 (08), 363 (08), 211 (03). IR (KBr): t 3427, 3042, 2952, 2927, 2867, 1725, 1660, 1588, 1522, 1495, 1450, 1339, 1283, 1218, 795, 746, 645 cm 1. HRMS: calculated for C32H24NNa: 446.1879; observed 446.1879. 2,16-Dimethyl-9-butyl-9H-aza[7]helicene (14): 1 H NMR (400 MHz, CDCl3): d 8.14–8.12 (d, J = 8.4 Hz, 2H), 8.01–7.96 (m, 4H), 7.87–7.85 (d, J = 8.4 Hz, 2H), 7.72–7.70 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 0.8 Hz, 2H), 7.06–7.04 (dd, J = 8.0, 1.2 Hz, 2H), 4.81–4.77 (t, J = 6.8 Hz, 2H), 2.15–2.07 (m, 2H), 1.59–1.54 (m, 2H), 1.44 (s, 6H), 1.04–1.02 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 139.15, 132.32, 129.85, 129.69, 127.79, 127.61, 126.75, 126.70, 126.38, 126, 125.83, 123.76, 116.73, 109.43, 43.42, 31.99, 20.80, 20.71, 13.99. IR (KBr): 3435, 3042, 2957, 2917, 1722, 1584, 1508, 1339, 1155, 891, 831, 772, 647, 556 cm 1. HRMS: calculated for C34H29N 452.2371; observed 452.2372. 2,16-Dimethoxy-9-butyl-9H-aza[7]helicene (15): 1 H NMR (400 MHz, CDCl3): d 8.13–8.11 (d, J = 8.4 Hz, 2H), 8.03–8.01 (d, J = 8.4 Hz, 2H), 7.97–7.95 (d, J = 8.4 Hz, 2H), 7.84–7.82 (d, J = 8.8 Hz, 2H),
G. M. Upadhyay et al. / Tetrahedron Letters 55 (2014) 5394–5399 7.83–7.81 (d, J = 7.6 Hz, 2H), 7.45–7.43 (d, J = 8.4 Hz, 2H), 7.20–7.16 (ddd, J = 8.0, 6.8, 1.2 Hz, 2H), 6.26–6.21 (ddd, J = 8.4, 6.8, 1.2 Hz, 2H), 4.79–4.75 (t, J = 7.2 Hz, 2H), 2.13–2.04 (m, 2H), 1.59–1.49 (m, 2H), 1.04–1.00 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 139.32, 131.29, 130.23, 128.25, 127.09, 126.75, 126.69, 126.61, 126.22, 125.92, 124.25, 122.63, 116.75, 109.62, 43.43, 31.93, 20.71, 13.99. MS (EI): m/z, (%) 423 (100), 380 (34), 379 (15), 378 (04), 377 (06), 366 (13), 364 (08), 363 (08), 211 (03). IR (KBr): t 3427, 3042, 2952, 2927, 2867, 1725, 1660, 1588, 1522, 1495, 1450, 1339, 1283, 1218, 795, 746, 645 cm 1. HRMS: Calculated for C34H29NO2Na 506.2091; Observed 506.2090.
5399
2,16-Difluoro-9-butyl-9H-aza[7]helicene (16): 1 H NMR (400 MHz, CDCl3): d 8.15–8.13 (d, J = 8.4 Hz, 2H), 8.04–7.98 (m, 4H), 7.9–7.84 (m, 4H), 7.09–7.06 (dd, J = 11.6, 2.8 Hz, 2H), 7.03–6.99 (m, 2H), 4.79– 4.76, (t, J = 7.2 Hz, 2H), 2.13–2.06 (m, 2H), 1.57–1.54 (m, 2H), 1.05–1.02 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 159.82, 157.41, 139.25, 131.15, 131.06, 128.5, 128.41, 127.04, 126.67, 126.18, 126.16, 123.92, 116.18, 114.95, 114.71, 112.34, 112.11, 110.32, 43.5, 31.97, 20.69, 13.96. 19 F NMR (376 MHz, CDCl3): d 117.38. IR (KBr): t 3019, 2960, 1684, 1599, 1504, 1215, 832, 757, 668 cm 1. HRMS: calculated for C32H23NF2: 460.1874; observed 460.1871.
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Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthesis of carbazole derived aza[7]helicenes Gourav M. Upadhyay a, , Harish R. Talele a, , Sibaprasad Sahoo b, Ashutosh V. Bedekar a,⇑ a b
Department of Chemistry, Faculty of Science, M. S. University of Baroda, Vadodara 390 002, India Sun Pharma Advanced Research Centre, Tandalja, Vadodara 390 020, India
a r t i c l e
i n f o
Article history: Received 24 June 2014 Revised 27 July 2014 Accepted 28 July 2014 Available online 2 August 2014 Keywords: Aza[7]helicene Photocyclization Carbazole Mizoroki–Heck coupling One-pot Wittig–Heck reaction
a b s t r a c t Synthesis of four derivatives of symmetrical aza[7]helicenes is achieved by I2-THF mediated photocyclization of corresponding bis-styryl derivatives. The cyclization furnished the desired angularly fused azahelicene in moderate yields. The structures are established by NMR spectroscopy and single crystal X-ray analysis for the difluoro derivative. The series of synthesized aza[7]helicenes showed remarkable thermal stability as indicated by DSC analysis. Ó 2014 Elsevier Ltd. All rights reserved.
Molecules possessing ortho-fused aromatic rings, acquire a unique shape in order to release the internal strain. This type of molecular arrangement acquires helical structure and shows stereoisomerism. The helical molecules have attracted much attention in recent years due to some unique properties associated with their structure.1 The efficient delocalization of p-electrons and non-planarity of the structure in helicenes enable them to be stable to strong acids and high temperature. Applications of helical molecules cover a wide range in fields of material science,2 asymmetric synthesis and catalysis,3 as molecular motor,4 in biology5 etc. A number of approaches have been developed for the synthesis of these screw shaped molecules due to efforts required to overcome the inherent steric factors or steric crowding. Therefore, the synthesis of new helical molecules remains an exciting challenge and a rewarding endeavor. Helical or helicene like molecules possessing heteroatoms are of considerable interest due to the additional properties. Although considerable attention has been devoted to the thia-helicenes,6 the aza-helicenes, containing one or more nitrogen atom, have also gained interests.7 Most of these aza-helicenes or aza-helicene like compounds are derivatives of pyridine, but only a few analogues of pyrrole (pyrrolohelicenes) are studied. The first example, pyrrolo[5]helicene I (Fig. 1), was reported by Meisenheimer and Witte,8 way back in early 20th century, which was followed by a report on the synthesis of pyrrolo[6]helicene II by Fuchs and Niszel.9a
NH
NH
HN
N CH 6 13
N C6H13 I (Meisenheimer 1903)
II (Fuchs 1927)
III (Liu 2012)
Br
N R
NPh IV (Nozaki 2005)
N Me V (Hassine 2013)
N R
VI (List 2014)
Figure 1. Known carbazole-based azahelicenes.
R'' R''
R'' R''
N
N
R' aza[7]helicene
R'
Figure 2. Retrosynthetic scheme for aza[7]helicene
⇑ Corresponding author. Tel.: +91 265 2795552.
E-mail address: [email protected] (A.V. Bedekar). These authors contribute equally.
http://dx.doi.org/10.1016/j.tetlet.2014.07.116 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Later the same type of compound was synthesized and resolved by Pischel et al.9b Lately another derivative III was synthesized
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I
R''
R''
I
R'' R''
N H
N R'
1
hu I2-THF
2, R' = n-Bu
R''
R'' R'' 3, R'' = H; 4, R'' = Me 2
Toluene 24 h
N
N
R'
R'
5, R' = n-Bu; R'' = H 6, R'= n-Bu; R'' = Me 9, R' = n-Bu; R'' = OMe 12, R' = n-Bu; R'' = F
13, R' = n-Bu; R'' = H (44 %) 14, R' = n-Bu; R'' = Me (40 %) 15, R' = n-Bu; R'' = OMe (44 %) 16, R' = n-Bu; R'' = F (37 %)
Scheme 3. Photocyclization of distyryl carbazoles.
Pd(OAc)2 - dppp K2CO3
N
140 oC, 48 h
R' 5, R' = n-Bu, R'' = H (94 %) 6, R' = n-Bu, R'' = Me (87 %)
Scheme 1. Synthesis of (E,E) 3,6-distyryl-9-butyl-9H-carbazoles by Mizoroki–Heck reaction.
and investigated as deep-blue-emitting OLED by Liu et al.10 This particular diaza[7]helicene consists of two linear and angularly cyclized units of carbazole moiety. However, the angularly cyclized aza[7]helicene IV has been previously reported by Nozaki.11 The synthesis was independently reported by Pd catalyzed coupling reactions. Another pyrrolo[5]helicene V system was recently prepared by Hassine et al.12 which consisted of an unsymmetric unit of carbazole. Very recently List and co-workers13 have efficiently synthesized bis-azahelicene VI, along with other derivatives with an elegant use of organocatalysts for double Fischer indolizationoxidation protocol. The synthesis has also been extended to asymmetric version by using chiral phosphoric acid catalyst. Considering the large interest in the field of helical molecules these form a small group of examples of pyrrole based heterohelicenes and the area still remains scarcely explored. In continuation of our work on photocyclization14 and helicenelike molecules,15,16 this Letter presents the synthesis of symmetrical aza[7]helicenes. The retrosynthetic plan to access these molecules indicates the possible option of oxidative double photocyclization of stilbene type analogues of carbazole (Fig. 2). The required starting material for the photoreaction can be easily prepared by Mizoroki–Heck reaction of 3,6-diiodo-9-alkyl-9H-carbazole with appropriate styrene. By choosing a suitable styrene, different functional groups can be introduced on aza[7]helicenes and can be a general preparative method. The earlier synthesis of similar aza[7]helicene was performed by different methods of cyclization.11
The required starting material 3,6-diiodo-9-butyl-9H-carbazole 2 was prepared from carbazole 1 by known procedures.17 To increase the solubility of resultant aza[7]helicene the n-Bu group was selected.18 It was then subjected to double Mizoroki–Heck reaction in the presence of palladium catalyst, dppp, K2CO3, and styrene 3, in order to obtain corresponding (E,E)-3,6-distyryl-9butyl-9H-carbazole 5 in excellent yields.19 A similar scheme with 4-methyl styrene 4 was followed to prepare the corresponding dimethyl derivative 6 (Scheme 1). However, this option has the limitation of the availability of the required styrene derivative for the Mizoroki–Heck reaction. Some substituted styrenes are not readily available or are unstable, hence to overcome this problem we have recently developed a protocol of making them in situ for a one-pot reaction.20 In this process an aldehyde with required substituent was subjected to the Wittig reaction with a one carbon phosphonium salt (Ph3PCH3I) to generate the desired styrene derivative, which was further subjected to Mizoroki–Heck condition in the same flask to give the stilbene derivative. This new methodology is advantageous due to the availability of substituted aldehydes which can compensate for the poor accessibility of certain styrenes. This process was also applied for the synthesis of two more derivatives of the present distyryl carbazoles. In this way a method can be developed to prepare any type of (E,E)-3,6-distyryl-9-alkyl-9H-carbazole required for the synthesis of aza[7]helicene. In the present work two derivatives from 4-methoxy benzaldehyde 7 and 4-fluoro benzaldehyde 10 are utilized to prepare 4-methoxy styrene 8 and 4-fluoro styrene 11, respectively, which were in situ subjected to one-pot Mizoroki–Heck reaction with 2 (Scheme 2). The distyryl derivative of carbazole 5 obtained was subjected to photocyclization in toluene with the high pressure mercury vapor lamp. The reaction was carried out in the presence of stoichiometric amount of iodine as an oxidizing agent and THF as a scavenger of the hydrogen iodide formed.14 Careful analysis of the reaction mixture revealed consumption of the starting material and forma-
R''
R''
CHO
R''
Ph3PCH3I
2
K2CO3
Pd(OAc)2 - dppp K2CO3 140 oC, 48 h
R''
7, R'' = OMe 10, R'' = F
8, R'' = OMe 11, R'' = F
N R' 9, R' = n-Bu; R'' = OMe (87 %) 12, R' = n-Bu; R'' = F (52 %)
Scheme 2. Synthesis of (E,E) 3,6-distyryl-9-butyl-9H-carbazoles by one-pot Wittig–Heck reaction.
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Figure 3. ORTEP plot of 16.
Table 1 Select X-ray crystallographic data of the compound 1621
a
Inner carbon–carbon bond lengths (Å) C17c–C17d C17d–C17e C17e–C17f C1–C17f
1.455 1.424 1.440 1.403
Distance between non bonded atoms (°) F22–F23 C3–C15 C2–C16 C1–C17
5.432 4.446 3.913 3.003
Outer carbon–carbon bond length (Å) C3–C4 C5–C6 C7–C8
1.358 1.332 1.342
C17a–C17f C17b–C17e C11–C12 C13–C14
3.529 3.559 2.444 2.454
Torsion angle (°) u 1 = C17–C17a–C17b–C17c u 2 = C17a–C17b–C17c–C17d u 3 = C17b–C17c–C17d–C17e
14.83 17.03 17.27
Distortion of the molecular structure (°) u 1+u 2+u 3
49.13
Dihedral angle h (°)a
35.84
Angle between planes passing through C1–C2–C3–C4–C4a–C17f and C13a–C14–C15–C16–C17–C17a rings.
tion of a major product, which was isolated by column chromatography over silica gel. The 1H NMR analysis of 13 clearly established the double angular cyclization (Scheme 3). Photocyclization was also extended to other three derivatives 6, 9, and 12 to afford similarly cyclized aza[7]helicenes 14, 15, and 16 respectively in moderate yields. In all the cases the double angularly fused systems were isolated and characterized by 1H NMR analysis and supported by other spectral techniques. The hydrogen attached to C4 (& C5) of 5 appeared at 8.3 d as a singlet disappeared in 13 on cyclization. This is a clear evidence of angular cyclization. In compound 13 the inside protons attached to C2 (& C16) appeared most upfield in the aromatic region at 6.21-6.28 d, followed by signal at 7.16-7.20 d for
Table 2 Prominent UV–vis bands of 13–16 Compound
Figure 4. UV–visible spectra of aza[7]helicenes.
13 14 15 16
Wavelength (nm) 260 261 260 257
326 326 318 315
335 333 330 327
385 388 394 390
401 404 414 408
G. M. Upadhyay et al. / Tetrahedron Letters 55 (2014) 5394–5399
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Figure 5. DSC thermogram of aza[7]helicenes 13 to 16.
Table 3 Thermal behavior of 13–16 by DSC analysis Compound
Melting point (°C)
Glass Transition Temperature Tg (°C)
13 14 15 16
208.9 246.0 200.5 210.7
151.0 197.3 147.5 173.1
the protons attached to C3 (& C15). The other two protons attached to C1 (& C17) and C4 (& C14) of the terminal rings appeared at 7.43–7.45 and 7.81–7.83 d. All the four aza[7]helicenes are quite soluble in organic solvents such as toluene, dichloromethane, chloroform, acetone, and ethyl acetate. A pale yellow crystal of 16 was obtained from ethyl acetate-hexane and analyzed by single crystal X-ray diffraction (Fig. 3).21 Select bond lengths, distances of non-bonded atoms, and torsion angles are presented in Table 1. Some of the bonds of the outer side C3–C4, C5–C6, and C7–C8 were of the order of 1.332–1.358 Å, much shorter compared to the average bond of benzene (1.39 Å). For helicene structure, as expected the inside bond lengths were found to be elongated in the range of 1.403– 1.455 Å. The distance between the non-bonded atoms of the last two terminal rings of this compound clearly indicated that they were separated by about 4 Å. The two carbon atoms bearing fluorine (C2–C16) were seen to be separated by 3.913 Å and the fluorine atom was located almost beneath the last aromatic ring of aza[7]helicene structure. The distance between C11-C12 and C13-C14 was in the range of 2.444-2.454 Å which is shorter than the corresponding C1-C10 of phenanthrene (2.473 Å). This marginal decrease was due to the helical shape of the molecule and contributed in the upfield shift in the 19F NMR spectra. This could be due to the shielding effect of the ring. The torsion angle along the inner frame of aza[7]helicene varied from 14.83 to 17.27, a characteristic measure of helicity. The sum of the three dihedral angles u 1, u 2, and u 3 was observed to be 49.13°, which is considered to be quite pronounced and may offer good rigidity to isomers. The analysis of 16 on chiral phase HPLC supported this observation where the two well separated peaks for the helical isomers were detected [Chiralcel OD-H; IPA in hexane (10%), 1.0 mL/ min, 6.5 and 8.3 min].
The aza[7]helicene derivatives were investigated using UV–vis absorption study performed in methanolic solution (5.0 10 5 mol). Spectra of these compounds exhibited a strong absorption in the region of 257–414 nm (Fig. 4). The analysis was in accordance with the expected values and several significant absorption bands were observed (Table 2). Thermal behavior of aza[7]helicenes was investigated by means of differential scanning calorimetry (DSC) where the sample was heated at the rate if 10 °C/min from 25 to 300 °C, under the inert atmosphere of nitrogen (Fig. 5). The analysis indicated the melting point of compounds to be in the range of 200–246 °C. The glass transition temperatures (Tg) of aza[7]helicenes lie in 147–197 °C (Table 3), which point toward high thermal stability of the helical system. It is noteworthy to observe higher values of Tg for the present aza[7]helicenes as compared to the earlier reported aza[5]helicene.12 In summary an efficient method has been developed for preparing aza[7]helicene by double angular photocyclization of distyryl carbazoles.22 Products are well characterized to establish the structure and the associated helicity. The series of aza[7]helicenes synthesized showed remarkable thermal stability as measured by DSC analysis. Acknowledgments We wish to thank the Science and Engineering Research Board (SERB), New Delhi for the financial assistance for this work [No. SR/S1/OC-74/2012]. We also thank the Department of Science and Technology (DST), New Delhi for the PURSE project under which the X-Ray Diffraction Machine was acquired in the Faculty of Science. References and notes 1. (a) Grimme, S.; Harren, J.; Sobanski, A.; Vögtle, F. Eur. J. Org. Chem. 1998, 1491– 1509; (b) Urbano, A. Angew. Chem., Int. Ed. 2003, 42, 3986–3989; (c) Collins, S. K.; Vachon, M. P. Org. Biomol. Chem. 2006, 4, 2518–2524; (d) Rajca, A.; Miyasaki, M. In Functional Organic Materials; Muller, T. J. J., Bunz, U. H. F., Eds.; WileyVCH: Weinheim, 2007; pp 547–581; (e) Shen, Y.; Chen, C.-F. Chem. Rev. 2012, 112, 1463–1535; (f) Gingras, M. Chem. Soc. Rev. 2013, 42, 968–1006; (g) Gingras, M.; Félix, G.; Peresutti, R. Chem. Soc. Rev. 2013, 42, 1007–1050; (h) Gingras, M. Chem. Soc. Rev. 2013, 42, 1051–1095.
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Kötzner, L.; Webber, M. J.; Martínez, A.; De Fusco, C.; List, B. Angew. Chem., Int. Ed. 2014, 53, 5205. 14. Talele, H. R.; Gohil, M. J.; Bedekar, A. V. Bull. Chem. Soc. Jpn. 2009, 82, 1182– 1186. 15. (a) Talele, H. R.; Sahoo, S.; Bedekar, A. V. Org. Lett. 2012, 14, 3166–3169; (b) Talele, H. R.; Bedekar, A. V. Org. Biomol. Chem. 2012, 10, 8579–8582. 16. Shyam Sundar, M.; Talele, H. R.; Mande, H. M.; Bedekar, A. V.; Tovar, R. C.; Muller, G. Tetrahedron Lett. 2014, 55, 1760–1764. 17. (a) Chuang, C.-N.; Chuang, H.-J.; Wang, Y.-X.; Chen, S.-H.; Huang, J.-J.; Leung, M.-K.; Hsieh, K.-H. Polymer 2012, 53, 4983–4992; (b) Liu, X.; Sun, Y.; Zhang, Y.; Zhao, N.; Zhao, H.; Wang, G.; Yu, X.; Liu, H. J. Fluoresc. 2011, 21, 497–506. 18. Zhao, T.; Liu, Z.; Song, Y.; Xu, W.; Zhang, D.; Zhu, D. J. Org. Chem. 2006, 71, 7422–7432. 19. Carbi, W.; Candiani, I.; Bedeschi, A.; Penco, S.; Santi, R. J. Org. Chem. 1992, 57, 1481–1486. 20. (a) Saiyed, A. S.; Bedekar, A. V. Tetrahedron Lett. 2010, 51, 6227–6231; (b) Bedekar, A. V.; Chaudhary, A. R.; Shyam Sundar, M.; Rajappa, M. Tetrahedron Lett. 2013, 54, 392–396. 21. Crystallographic data for the structures of compound 16 has been deposited with the Cambridge Crystallographic Data Centre (CCDC No. 1004161). Copies of the data can be obtained from http://www.ccdc.cam.ac.uk/conts/ retrieving.html or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CD21EZ, UK (fax: +44-1223-336-033; e-mail: [email protected]). Atom numbers in Figure 3 are assigned based on IUPAC rules and are different from the pattern in ORTEP data submitted to CCDC. 22. Synthesis of 3,6-distyryl-9-butyl-9H-carbazole (5) by Mizoroki–Heck reaction: A solution of palladium acetate (0.009 g, 0.042 mmol, 2 mol %) and 1,3bis(diphenylphosphinopropane) (0.034 g, 0.084 mmol, 4 mol %) was prepared in N,N-dimethylacetamide (5 mL) under nitrogen atmosphere. The mixture was stirred at room temperature until a homogeneous solution was obtained. This catalyst solution was repeatedly purged by N2 prior to use. A two-necked round bottom flask was charged with 3,6-diiodo-Nbutylcarbazole (1.0 g, 2.1 mmol), dry potassium carbonate (1.16 g, 8.4 mmol),
TBAB (0.135 g, 0.42 mmol, 20 mol %), and N,N-dimethylacetamide (10 mL). The solution was repeatedly purged with N2. Styrene (0.546 g, 5.25 mmol) was added at 60 °C and the mixture was heated up to 100 °C. At 100 °C, the previously prepared Pd catalyst solution was added dropwise and the mixture was further heated to 140 °C for 48 h. After the completion of the reaction, the mixture was poured into ice-cold water and extracted with dichloromethane (3 x 100 mL). The combined organic phase was washed with water, brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel using petroleum ether–ethyl acetate (98:2) as eluent to afford predominantly trans isomer of 3,6-distyryl-N-butylcarbazole. 0.845 g (94%); mp 152–156 °C. 1 H NMR (400 MHz, CDCl3): d 8.30 (s, 2H), 7.72–7.69 (dd, J = 8.8, 1.6 Hz, 2H), 7.63–7.61 (d, J = 7.6 Hz, 4H), 7.45–7.28 (m, 9H), 7.23–7.19 (d, J = 16.4 Hz), 4.32–4.28 (t, J = 7.2, 2H), 1.91–1.85 (q, 2H), 1.48–1.40 (m, 2H), 1.01–0.97 (t, J = 7.2 Hz, 3H). MS (EI): m/z, (%) 428 (83), 427 (24), 426 (100), 385 (55). IR (KBr): t 3438, 3023, 2954, 2867, 1725, 1623, 1592, 1484, 1382, 1341, 1244, 1208, 1153, 1130, 1070, 959, 881, 802, 751, 690 cm 1. Synthesis of 3,6-di(4-methoxystyryl)-9-butyl-9H-carbazole (9) by one-pot Wittig– Heck reaction: A solution of palladium acetate (0.010 g, 0.042 mmol, 2 mol %) and 1,3bis(diphenylphosphinopropane) (0.034 g, 0.084 mmol, 4 mol %) was prepared in N,N-dimethylacetamide (5 mL) under nitrogen atmosphere. The mixture was stirred at room temperature until a homogeneous solution was obtained. This catalyst solution was repeatedly purged by N2 prior to use. A two-necked round bottom flask was charged with 3,6-diiodo-Nbutylcarbazole (1.0 g, 2.10 mmol), 4-methoxy benzaldehyde 7 (0.715 g, 5.26 mmol), methyltriphenylphosphonium iodide (2.56 g, 6.31 mmol), dry potassium carbonate (2.18 g, 15.7 mmol), TBAB (0.135 g, 0.42 mmol, 20 mol %), and N,N-dimethylacetamide (10 mL) and the mixture was heated up to 100 °C. At 100 °C, the previously prepared Pd catalyst solution was added dropwise and the mixture was heated to 140 °C for 48 h. After the completion of the reaction similar work-up procedure was followed as discussed above. Pure product was isolated by column chromatography on silica gel using petroleum ether–ethyl acetate (95:5) as eluent to afford predominantly trans isomer of 3,6-bis-(4-methoxystyryl)-N-butylcarbazole; 0.887 g (87%); mp 201– 203 °C. 1 H NMR (400 MHz, CDCl3): d 8.22–8.21 (d, J = 1.2 Hz, 2H), 7.63–7.61 (dd, J = 8.4, 1.2 Hz, 2H), 7.51–7.48 (d, J = 8.8 Hz, 4H), 7.34–7.32 (d, J = 8.4 Hz, 2H), 7.20– 7.16 (d, J = 16.4 Hz), 7.12–7.08 (d, J = 16.4 Hz, 2H), 6.93–6.91 (broad d, 4H), 4.27–4.23 (t, J = 7.2, 2H), 3.83 (s, 6H), 1.87–1.80 (m, 2H), 1.42–1.33 (m, 2H), 0.98–0.91 (t, J = 7.2 Hz, 3H). MS (EI): m/z, (%) 489 (10), 488 (29), 487 (100), 486 (42), 485 (47), 445 (10), 444 (13), 443 (16), 428 (08), 341 (06), 243 (10), 136 (12), 95 (16). IR (KBr): t 3429, 3020, 2957, 1872, 1604, 1482, 1383, 1344, 1301, 1246, 1175, 1109, 1033, 961, 851, 818, 760 cm 1. General procedure for photocyclodehydrogenation:14 Synthesis of N-butylaza[7]helicene (13): A solution of 3,6-distyryl-N-butylcarbazole 5 (0.350 g, 0.82 mmol), iodine (0.457 g, 1.80 mmol), dry THF (2.95 g, 3.32 mL, 41.3 mmol), and toluene (1.2 L) was irradiated using a 125 W HMPV lamp (24 h monitored by tlc). After the completion of the reaction, the excess of iodine was removed by washing the solution with aqueous Na2S2O3 and water. The organic layer was concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography over silica gel using petroleum ether– ethyl acetate (98:2) as eluent to obtain a pale yellow solid. 0.151 g (44%); mp 214–215 °C. 1 H NMR (400 MHz, CDCl3): d 8.13–8.11 (d, J = 8.4 Hz, 2H), 8.03–8.01 (d, J = 8.4 Hz, 2H), 7.97–7.95 (d, J = 8.4 Hz, 2H), 7.84–7.82 (d, J = 8.8 Hz, 2H), 7.83–7.81 (d, J = 7.6 Hz, 2H), 7.45–7.43 (d, J = 8.4 Hz, 2H), 7.20–7.16 (ddd, J = 8.0, 6.8, 1.2 Hz, 2H), 6.26–6.21 (ddd, J = 8.4, 6.8, 1.2 Hz, 2H), 4.79–4.75 (t, J = 7.2 Hz, 2H), 2.13–2.04 (m, 2H), 1.59–1.49 (m, 2H), 1.04–1.00 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 139.32, 131.29, 130.23, 128.25, 127.09, 126.75, 126.69, 126.61, 126.22, 125.92, 124.25, 122.63, 116.75, 109.62, 43.43, 31.93, 20.71, 13.99. MS (EI): m/z, (%) 423 (100), 380 (34), 379 (15), 378 (04), 377 (06), 366 (13), 364 (08), 363 (08), 211 (03). IR (KBr): t 3427, 3042, 2952, 2927, 2867, 1725, 1660, 1588, 1522, 1495, 1450, 1339, 1283, 1218, 795, 746, 645 cm 1. HRMS: calculated for C32H24NNa: 446.1879; observed 446.1879. 2,16-Dimethyl-9-butyl-9H-aza[7]helicene (14): 1 H NMR (400 MHz, CDCl3): d 8.14–8.12 (d, J = 8.4 Hz, 2H), 8.01–7.96 (m, 4H), 7.87–7.85 (d, J = 8.4 Hz, 2H), 7.72–7.70 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 0.8 Hz, 2H), 7.06–7.04 (dd, J = 8.0, 1.2 Hz, 2H), 4.81–4.77 (t, J = 6.8 Hz, 2H), 2.15–2.07 (m, 2H), 1.59–1.54 (m, 2H), 1.44 (s, 6H), 1.04–1.02 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 139.15, 132.32, 129.85, 129.69, 127.79, 127.61, 126.75, 126.70, 126.38, 126, 125.83, 123.76, 116.73, 109.43, 43.42, 31.99, 20.80, 20.71, 13.99. IR (KBr): 3435, 3042, 2957, 2917, 1722, 1584, 1508, 1339, 1155, 891, 831, 772, 647, 556 cm 1. HRMS: calculated for C34H29N 452.2371; observed 452.2372. 2,16-Dimethoxy-9-butyl-9H-aza[7]helicene (15): 1 H NMR (400 MHz, CDCl3): d 8.13–8.11 (d, J = 8.4 Hz, 2H), 8.03–8.01 (d, J = 8.4 Hz, 2H), 7.97–7.95 (d, J = 8.4 Hz, 2H), 7.84–7.82 (d, J = 8.8 Hz, 2H),
G. M. Upadhyay et al. / Tetrahedron Letters 55 (2014) 5394–5399 7.83–7.81 (d, J = 7.6 Hz, 2H), 7.45–7.43 (d, J = 8.4 Hz, 2H), 7.20–7.16 (ddd, J = 8.0, 6.8, 1.2 Hz, 2H), 6.26–6.21 (ddd, J = 8.4, 6.8, 1.2 Hz, 2H), 4.79–4.75 (t, J = 7.2 Hz, 2H), 2.13–2.04 (m, 2H), 1.59–1.49 (m, 2H), 1.04–1.00 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 139.32, 131.29, 130.23, 128.25, 127.09, 126.75, 126.69, 126.61, 126.22, 125.92, 124.25, 122.63, 116.75, 109.62, 43.43, 31.93, 20.71, 13.99. MS (EI): m/z, (%) 423 (100), 380 (34), 379 (15), 378 (04), 377 (06), 366 (13), 364 (08), 363 (08), 211 (03). IR (KBr): t 3427, 3042, 2952, 2927, 2867, 1725, 1660, 1588, 1522, 1495, 1450, 1339, 1283, 1218, 795, 746, 645 cm 1. HRMS: Calculated for C34H29NO2Na 506.2091; Observed 506.2090.
5399
2,16-Difluoro-9-butyl-9H-aza[7]helicene (16): 1 H NMR (400 MHz, CDCl3): d 8.15–8.13 (d, J = 8.4 Hz, 2H), 8.04–7.98 (m, 4H), 7.9–7.84 (m, 4H), 7.09–7.06 (dd, J = 11.6, 2.8 Hz, 2H), 7.03–6.99 (m, 2H), 4.79– 4.76, (t, J = 7.2 Hz, 2H), 2.13–2.06 (m, 2H), 1.57–1.54 (m, 2H), 1.05–1.02 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDCl3): d 159.82, 157.41, 139.25, 131.15, 131.06, 128.5, 128.41, 127.04, 126.67, 126.18, 126.16, 123.92, 116.18, 114.95, 114.71, 112.34, 112.11, 110.32, 43.5, 31.97, 20.69, 13.96. 19 F NMR (376 MHz, CDCl3): d 117.38. IR (KBr): t 3019, 2960, 1684, 1599, 1504, 1215, 832, 757, 668 cm 1. HRMS: calculated for C32H23NF2: 460.1874; observed 460.1871.