Letter pubs.acs.org/OrgLett
Visible-Light-Induced Synthesis of Carbazoles by in Situ Formation of Photosensitizing Intermediate Tanmay Chatterjee,† Geum-bee Roh,† Mahbubul Alam Shoaib,‡ Chang-Heon Suhl,§ Jun Soo Kim,*,‡ Cheon-Gyu Cho,*,§ and Eun Jin Cho*,† †
Department of Chemistry, Chung-Ang University, Seoul 06974, Republic of Korea Department of Chemistry & Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea § Department of Chemistry, Hanyang University, Seoul 04763, Republic of Korea ‡
S Supporting Information *
ABSTRACT: A visible-light-induced synthesis of N-H carbazoles from easily accessible 2,2′-diaminobiaryls in the absence of any external photosensitizer is reported. The process only requires tBuONO and natural resources, visible light, and molecular oxygen for the synthesis of NH carbazoles. Experimental and computational studies support that the in situ formation of a visible-light-absorbing photosensitizing intermediate, benzocinnoline N-imide, is responsible for the activation of triplet molecular oxygen to singlet oxygen that, in turn, promotes the synthesis of carbazole.
Scheme 1. Design of a New Synthetic Strategy for N-H Carbazoles from 2,2′-Diamino-1,1′-biaryls
O
ver the past decade, various synthetic methods have been developed that utilize visible light to drive organic reactions.1 However, because of the inability of many organic molecules to absorb visible light, the success of the development of visible-light-induced synthesis has largely relied on the use of an external photosensitizer (PS) that absorbs the visible-light energy and utilizes it for the transformation of non-photoabsorbing organic reactants into products, either through electron transfer or energy transfer.1,2 In recent years, several external PS-free, visible-light-induced synthetic methods have been developed by utilizing the photochemical activity of various electron donor− acceptor (EDA) complexes that can generate radical species for further synthetic transformations by single-electron-transfer (SET) processes.3 The Melchiorre group showed that in situ formation of chiral enamines can directly act as a PS without relying on EDA chemistry.4 The Glorius5a and the Hong5b groups demonstrated that the substrates and/or products of a chemical reaction can also act as a PS in the visible-light induced processes. In this study, we propose a visible-light-induced synthesis of carbazole2a,6 utilizing easily accessible 2,2′-diaminobiaryls7,8 and a nitrite source that occurs autonomously by in situ formation of a photosensitizing intermediate without requiring any external PS. Carbazoles are valuable heterocycles in many applications because of their ubiquity in numerous bioactive natural products, pharmaceutical agents, and diverse novel functional materials.9,10 The in situ diazotization of 2,2′-diaminobiphenyl (1a) generates intermediate I, which undergoes intramolecular cyclization to produce highly conjugated nitrogen-rich tricyclic intermediates, N-H dibenzo[d,f ][1,2,3]triazepine (II), and benzocinnoline N-imide (III), which remain in equilibrium by rearrangement (Scheme 1). In the 1970s, the Rees group reported © XXXX American Chemical Society
the formation of II and III from the reactions of 2,2′diaminobiphenyl (1a), and some other products were also obtained under their conditions.11 We hypothesized that II and/ or III might work as a visible-light-absorbing photosensitizer to sensitize triplet molecular oxygen to its higher energy singlet state (1O2), which in turn could convert II to N-H carbazole (2a). The design of such a protocol originated from the well-known fact that highly conjugated and heteroatom (N,O,S)-containing organic molecules such as porphyrins, rose bengal, eosin, and methylene blue are very effective PSs for the activation of molecular oxygen that, in turn, promotes chemical reactions.12 To our delight, the reaction of 2,2′-diaminobiphenyl 1a with 1.5 equiv of tBuONO in oxygen atmosphere under visible-light [24 W compact fluorescent lamp (CFL)] irradiation produced NReceived: March 7, 2017
A
DOI: 10.1021/acs.orglett.7b00681 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
formed intermediate obtained from 1a can possibly work as PS in the presence of visible light and molecular oxygen. To determine the PS of the reaction, first the time-dependent density functional theory (TD-DFT) calculations of II and III were performed.13 A functional B3LYP level of theory was used in the calculations with a basis set of 6-311++g(d,p). The calculation results indicate that III has a significant absorption in the visible region with an absorption maximum at 376 nm whereas II did not absorb light in the visible region (Figure 2a). Fortunately, the PS
H carbazole 2a without external PS. Various solvents, including acetonitrile (MeCN), dimethylformamide (DMF), dimethyl sulfoxide (DMSO), MeOH, 2,2,2-trifluoroethanol (TFE), dichloromethane (DCM), and dichloroethane (DCE), were screened; DCE showed the best result (Scheme 2). When the Scheme 2. Preliminary Results of Carbazole Synthesis Using 1a under Visible-Light Irradiationa,b
a
Reaction scale: 0.1 mmol. bYields were determined by 1H NMR using bromoform as the internal standard.
Figure 2. (a) Calculated absorption spectra of II and III using TD-DFT with B3LYP/6-311++G(d,p) and (b) UV−vis spectra of III in DCE (10−4 M).
reaction mixture was completely deoxygenated by repeated vacuum−freeze−thaw cycles, no carbazole 2a was produced, confirming the critical role of molecular oxygen in the reaction. When the reaction was carried out in the dark, a trace amount of 2a was produced, confirming that the process is promoted by visible light. The use of blue LEDs as the visible light source or the use of CFL along with a 400 nm UV cutoff filter still worked but decreased the yield slightly, indicating that the PS would absorb light in the near-UV−vis region. Further optimization revealed that use of 1.3 equiv of tBuONO in 0.1 M DCE is optimum for this reaction. Notably, the use of an external PS like fac-Ir(ppy)3, facIr(dFppy)3, [Ru(bpy)3]Cl2, and Eosin Y did not improve the yield of 2a (for optimization details, see Table S1). To prove that the reaction is promoted by the in situ generated photosensitizing intermediate, the UV−vis spectra of the reaction mixture using 1a as the substrate were recorded at different times (Figure 1). A new broad peak appeared in the visible region above
candidate III could be isolated under dark conditions and characterized by 1H and 13C NMR spectroscopy and highresolution mass spectroscopy (HRMS). The UV−vis spectrum of III (Figure 2b) showed a significant absorption in the visible region with a maximum at 383 nm, similar to that of the reaction mixture of 1a (Figure 1) and also consistent with the calculation results. In addition, several experiments further confirmed that III is the intermediate of the reaction and works as a PS for the process. First, the isolated III was converted to N-H carbazole (2a) under oxygen atmosphere and visible-light irradiation, supporting that III is indeed one of the intermediates (Scheme 3a).14 Next, III was Scheme 3. Additional Experiments To Prove that III Is the Photosensitizing Intermediate of the Process
subjected to the reaction of benzyl alcohol 3. It is known that singlet oxygen generated by a PS under visible-light irradiation can lead to the oxidation of 3 to benzaldehyde 4.15 In the reaction of 3 with 5 mol % of III and molecular oxygen under visible-light irradiation (Scheme 3b), 4 was formed despite a low yield, indicating that III can act as a PS. The reaction of 3 did not proceed in the absence of either III or O2. To determine whether the reaction of 1a to 2a proceeds through a free-radical pathway, additional experiments were performed in the presence of radical scavengers including TEMPO and 1,4-dinitrobenzene. The reactions were found to be unaffected in terms of yield, thus supporting a concerted mechanism for the synthesis of carbazole through N−N and C−N bond cleavages in II, followed by the new C−N bond formation. Based on these results, we propose a reaction mechanism as outlined in Scheme 4. Among the proposed intermediates II and III, III was found to be the PS from the combined experimental
Figure 1. UV−vis spectra of 1a, 2a, and the reaction mixture of 1a were recorded at different time intervals (20 min, 4, 8, and 20 h) in DCE (10−4 M). Inset: plot of time-dependent change in absorption at 400 and 420 nm.
400 nm, with a maximum at 360 nm after 20 min of reaction. Then, the intensity of the peak decreased, whereas the intensity of the corresponding N-H carbazole 2a peak increased with reaction time, indicating the transient formation of a visible-lightabsorbing intermediate during the reaction and its conversion to 2a. The formation of photoabsorbing intermediate is clearly shown in the inset of Figure 1 from the absorbance values at 400 and 420 nm in the visible range. The results indicate that the in situ B
DOI: 10.1021/acs.orglett.7b00681 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 5. Substrate Scope of the Synthesis of N-H Carbazolesa,b
Scheme 4. Proposed Reaction Mechanism
and computational studies. Compound III is excited to its corresponding high-energy singlet state 1[III] by absorbing photons from visible light; subsequent intersystem crossing (ISC) produces a relatively lower energy and long-lived triplet state 3[III], which returns to its ground state by transferring its energy to the triplet oxygen (3O2), generating high-energy singlet oxygen (1O2). According to the literature reports,12b,16 1O2 can react with II by two possible pathways, ene reaction (path A) and [2 + 2]-cycloaddition (path B). The ene reaction produces a reactive intermediate II-A which immediately decomposes to Nhydroxycarbazole II-B17 in a concerted step through the homolytic cleavage of O−O, N−N, and C−N bonds followed by the formation of new C−N bond and hydrogen atom abstraction from any H atom sources present in the reaction medium. The concomitant liberation of molecular nitrogen would be the driving force for the process. Finally, II-B decomposes to more stable N-H carbazole 2a through homolytic N−O bond cleavage followed by H atom abstraction. On the other hand, in path B, [2 + 2]-cycloaddition of II with 1O2 produces highly reactive intermediate II-C that immediately decomposes to 2a through the homolytic cleavage of O−O, N− N, and C−N bonds followed by the formation of new C−N bond along with the generation of nitric oxide (•NO) or dinitrogen dioxide (N2O2) which subsequently oxidize to nitrogen dioxide. Despite the feasibility of both pathways, path A is more likely to be operative over path B because intermediate II-A is expected to have lower energy than II-C according to the theoretical study of the reaction of formal hydrazone with 1O2 done by the Greer group.16 Next, the substrate scope of the synthesis of free N-H carbazoles was investigated using various substituted 2,2′diamino-1,1′-biaryls (Scheme 5). Notably, this method using free amino groups avoids the need for additional N-protection and deprotection steps to synthesize free N-H carbazole derivatives.2a,9c In general, 10−25% of the corresponding benzo[c]cinnoline derivatives were also obtained as the side product. Halogen (−Br, −Cl, −F)-substituted 2,2′-diamino-1,1′biaryls produced the corresponding carbazoles (2b−d). In particular, 1-bromocarbazole 2b is a good precursor for the synthesis of various host materials for phosphorescent organic light-emitting diodes by further functionalization at the 1position.18 Substrates with various electron-withdrawing groups (such as −Br, −Cl, −F, −OCF3, −COMe, −CO2Me, −CN, and −NO2) smoothly underwent cyclization to furnish the desired carbazoles (2b−i). Regarding the reactivity of substrates with electron-donating substituents, although the reaction of a
a
Reaction scale: 0.3 mmol. bIsolated yield. c1.0 mmol scale. dReaction was performed at 80 °C.
substrate with a methyl substituent (para to the NH2 group), 5methyl-[1,1′-biphenyl]-2,2′-diamine (1j), produced 3-methyl9H-carbazole (2j) in 65% yield, the substrate with a methoxy (meta to the NH2 group) substituent, 4-methoxy-[1,1′-biphenyl]2,2′-diamine (1k), produced 2-methoxy-9H-carbazole (2k) in low yield (26%). The lower reactivity of 1k can be attributed to the stabilization of the corresponding diazonium salt by the resonance effect of the methoxy group. Increasing the reaction temperature to 80 °C did not significantly improve the yield of 2k. Similarly, the reaction of 4,4′-dimethoxy[1,1′-biphenyl]-2,2′diamine (1m) produced 2,7-dimethoxy-9H-carbazole (2m), an alkaloid (clausine V), in a low yield (30%). A substrate containing a heteroaromatic moiety, i.e., 2-(2-aminophenyl)pyridin-3-amine (1n), also participated in the transformation to furnish δcarboline (2n), the core moiety in anti-infective agents and bluephosphorescent organic light-emitting diodes.19 This method was also used to synthesize N-H benzo[c]carbazoles (Scheme 6). Regardless of the electron density of the substituents in the starting substrates (5a−d), the corresponding N-H benzo[c]carbazoles (6a−d) were synthesized in moderateto-good yields (55−70%). On the other hand, the reaction of [1,1′-binaphthalene]-2,2′-diamine (7) furnished 7H-dibenzo[c,g]carbazole (8) in a low yield (25%), probably because of the Scheme 6. Substrate Scope of the Synthesis of N-H Benzo[c]carbazolesa,b
a
C
Reaction scale: 0.3 mmol. bIsolated yield. DOI: 10.1021/acs.orglett.7b00681 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Escudero-Adán, E. C.; Melchiorre, P. Angew. Chem., Int. Ed. 2015, 54, 1485. (d) Sun, X.; Wang, W.; Li, Y.; Ma, J.; Yu, S. Org. Lett. 2016, 18, 4638. (e) Beatty, J. W.; Douglas, J. J.; Miller, R.; McAtee, R. C.; Cole, K. P.; Stephenson, C. R. J. Chem. 2016, 1, 456. (f) For a recent review, see: Lima, C. G. S.; Lima, T. M.; Duarte, M.; Jurberg, I. D.; Paixão, M. W. ACS Catal. 2016, 6, 1389. (g) Deng, Y.; Wei, X.-J.; Wang, H.; Sun, Y.; Noël, T.; Wang, X. Angew. Chem., Int. Ed. 2017, 56, 832. (4) Silvi, M.; Arceo, E.; Jurberg, I. D.; Cassani, C.; Melchiorre, P. J. Am. Chem. Soc. 2015, 137, 6120. (5) (a) Sahoo, B.; Hopkinson, M. N.; Glorius, F. Angew. Chem., Int. Ed. 2015, 54, 15545. (b) Kim, I.; Min, M.; Kang, D.; Kim, K.; Hong, S. Org. Lett. 2017, 19, 1394. (6) For visible-light-induced synthesis of carbazoles, see: (a) Hernandez-Perez, A. C.; Collins, S. K. Angew. Chem., Int. Ed. 2013, 52, 12696. (b) Yuan, Z.-G.; Wang, Q.; Zheng, A.; Zhang, K.; Lu, L.-Q.; Tang, Z.; Xiao, W.-J. Chem. Commun. 2016, 52, 5128. Also see ref 2a. (7) For examples of synthetic accessibility of 2,2′-diamino-1,1′-biaryls, see: (a) Lim, Y. − K.; Jung, J. − W.; Lee, H.; Cho, C. − G. J. Org. Chem. 2004, 69, 5778. (b) Schulz, L.; Enders, M.; Elsler, B.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Angew. Chem., Int. Ed. 2017, DOI: 10.1002/anie.20161261. (8) Previously, the Yamato group utilized 2,2′-diamino-1,1′-biaryls for the synthesis of carbazoles in the presence of perfluorinated sulfonic acid resin (50 wt % Nafion-H) at high temperature (200 °C): Yamato, T.; Hideshima, C.; Suehiro, K.; Tashiro, M.; Prakash, G. K. S.; Olah, G. A. J. Org. Chem. 1991, 56, 6248. (9) For examples of books and reviews on carbazoles, see: (a) Chakraborty, D. P.; Roy, S. Progress in the Chemistry of Organic Natural Products; Herz, W., Kirby, G. W., Steglich, W., Tamm, Ch., Eds.; Springer-Verlag: New York, 1991; Vol. 57, p 72. (b) Schmidt, A. W.; Reddy, K. R.; Knölker, H.-J. Chem. Rev. 2012, 112, 3193. (c) Roy, J.; Jana, A. K.; Mal, D. Tetrahedron 2012, 68, 6099. (10) For examples to show application of carbazole derivatives in novel functional materials, see: (a) Grazulevicius, J. V.; Strohriegl, P.; Pielichowski, J.; Pielichowski, K. Prog. Polym. Sci. 2003, 28, 1297. (b) Brunner, K.; van Dijken, A.; Börner, H.; Bastiaansen, J. J. A. M.; Kiggen, N. M. M.; Langeveld, B. M. W. J. Am. Chem. Soc. 2004, 126, 6035. (c) Liu, Z.; Guan, M.; Bian, Z.; Nie, D.; Gong, Z.; Li, Z.; Huang, C. Adv. Funct. Mater. 2006, 16, 1441. (11) (a) Gait, S. F.; Rees, C. W.; Storr, R. C. J. Chem. Soc. D 1971, 1545. (b) Gait, S. F.; Peek, M. E.; Rees, C. W.; Storr, R. C. J. Chem. Soc., Chem. Commun. 1972, 982. (c) Gait, S. F.; Peek, M. E.; Rees, C. W.; Storr, R. C. J. Chem. Soc., Perkin Trans. 1 1974, 1248. (d) Gait, S. F.; Peek, M. E.; Rees, C. W.; Storr, R. S. J. Chem. Soc., Perkin Trans. 1 1975, 19. (12) For examples of reviews on singlet oxygen, see: (a) DeRosa, M. C.; Crutchley, R. J. Coord. Chem. Rev. 2002, 233−234, 351. (b) Ghogare, A. A.; Greer, A. Chem. Rev. 2016, 116, 9994. (13) For the details of DFT calculations, see Figures S1−S4 and Tables S2−S4 in the SI. The DFT calculation was also performed for intermediate I, but the spectrum of I showed weak absorption in the visible region, which is negligible; see Figure S2. (14) Along with N-H carbazole, 24% of benzo[c]cinnoline was also formed from III through N−N bond cleavage by photolysis. (15) (a) Lang, X.; Chen, X.; Zhao, J. Chem. Soc. Rev. 2014, 43, 473. (b) Mehrabi-Kalajahi, S. S.; Hajimohammadi, M.; Safari, N. J. Iran. Chem. Soc. 2016, 13, 1069. (16) Rudshteyn, B.; Castillo, Á .; Ghogare, A. A.; Liebman, J. F.; Greer, A. Photochem. Photobiol. 2014, 90, 431. (17) II-B cannot absorb light in the visible region, which excludes its role as a PS for this reaction; see: Buxton, P. C.; Heaney, H.; Mason, K. G.; Sketchley, J. M. J. Chem. Soc., Perkin Trans. 1 1974, 2695. (18) Kim, S. M.; Byeon, S. Y.; Hwang, S.-H.; Lee, J. Y. Chem. Commun. 2015, 51, 10672. (19) (a) Mazu, T. K.; Etukala, J. R.; Jacob, M. R.; Khan, S. I.; Walker, L. A.; Ablordeppey, S. Y. Eur. J. Med. Chem. 2011, 46, 2378. (b) Im, Y.; Lee, J. Y. Synth. Met. 2015, 209, 24.
steric effect when forming the key intermediate (see II in Scheme 1). In conclusion, we developed an autonomous visible-lightinduced method for the synthesis of N-H carbazoles from easily available 2,2′-diaminobiaryls through the in situ formation of a visible-light-absorbing photosensitizing intermediate, benzocinnoline N-imide. Combined experimental and theoretical studies confirmed that in the presence of visible light benzocinnoline Nimide activates triplet molecular oxygen to generate singlet oxygen that plays a key role in carbazole synthesis by reacting with the dibenzo[d,f ][1,2,3]triazepine intermediate. This simple method has several advantages: (1) external PS-free protocol utilizing natural resources such as visible light and molecular oxygen, (2) direct synthesis of free N-H carbazoles without Nprotection/deprotection steps, (3) broad substrate scope with a high functional group tolerance under mild reaction conditions, and (4) no regioselectivity problem.
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b00681. DFT calculation details, additional experimental results, experimental details, analytical data of the synthesized compounds, and NMR spectra (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Jun Soo Kim: 0000-0001-8113-0605 Eun Jin Cho: 0000-0002-6607-1851 Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS This work was supported by the National Research Foundation of Korea (NRF-2014R1A1A1A05003274, 2014R1A5A1011165, and 2012M3A7B4049657).
■
REFERENCES
(1) For some recent reviews on visible-light-induced photocatalysis, see: (a) Yoon, T. P.; Ischay, M. A.; Du, J. Nat. Chem. 2010, 2, 527. (b) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102. (c) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (d) Koike, T.; Akita, M. Top. Catal. 2014, 57, 967. (e) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075. (f) Cambié, D.; Bottecchia, C.; Straathof, N. J. W.; Hessel, V.; Noël, T. Chem. Rev. 2016, 116, 10276. (2) For examples of our recent works on visible light photocatalysis, see: (a) Choi, S.; Chatterjee, T.; Choi, W. J.; You, Y.; Cho, E. J. ACS Catal. 2015, 5, 4796. (b) Chatterjee, T.; Choi, M. G.; Kim, J.; Chang, S.-K.; Cho, E. J. Chem. Commun. 2016, 52, 4203. (c) Choi, Y.; Yu, C.; Kim, J. S.; Cho, E. J. Org. Lett. 2016, 18, 3246. (d) Chatterjee, T.; Iqbal, N.; You, Y.; Cho, E. J. Acc. Chem. Res. 2016, 49, 2284. (3) For examples of visible-light-induced EDA chemistry and their application in synthetic organic chemistry, see: (a) Rosokha, S. V.; Kochi, J. K. Acc. Chem. Res. 2008, 41, 641. (b) Davies, J.; Booth, S. G.; Essafi, S.; Dryfe, R. A. W.; Leonori, D. Angew. Chem., Int. Ed. 2015, 54, 14017. (c) Kandukuri, S. R.; Bahamonde, A.; Chatterjee, I.; Jurberg, I. D.; D
DOI: 10.1021/acs.orglett.7b00681 Org. Lett. XXXX, XXX, XXX−XXX
