Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Oxidative Rearrangement of 3‑Aminoindazoles for the Construction of 1,2,3-Benzotriazine-4(3H)‑ones at Ambient Temperature Yao Zhou,† Ya Wang,† Yixian Lou,‡ and Qiuling Song*,†,‡ †
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Institute of Next Generation Matter Transformation, College of Chemical Engineering, College of Material Sciences Engineering, Huaqiao University, 668 Jimei Boulevard, Xiamen, Fujian 361021, P.R. China ‡ Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang 310000, P.R. China S Supporting Information *
ABSTRACT: A novel oxidative rearrangement of 3-aminoindazoles is reported, enabling the production of diverse functionalized 1,2,3-benzotriazine-4(3H)-ones in good yields at room temperature. The key success of this unprecedented transformation of 3-aminoindazoles is the use of water as cosolvent, which could facilitate the halogen-induced ring expansion of 3-aminoindazoles under oxidative conditions.
H
of such progress on halogen-induced migration rearrangement reactions, the rearrangement reactions in which the migration groups are N-centered rather than C-centered groups have been sparsely documented to date. 3-Aminoindazoles have thus far proven to be effective cyclization partners for the construction of various functionalized pyrimido[1,2-b]indazole derivatives.8 To our knowledge, the rearrangement reaction of 3-aminoindazoles has not been explored thus far. 1,2,3-Benzotriazine-4(3H)-ones have emerged as privileged core structural motifs in a diverse array of bioactive molecules and agrochemicals (Figure 1).9 Meanwhile, 1,2,3-benzotriazine-
alogen-induced rearrangement reactions represent a promising avenue that can give rise to a vast array of synthetically useful transformations.1−4 The earliest study involving halogen-mediated rearrangements can be dated back to Hofmann rearrangement,2 which provides a reliable approach to access diverse primary amines from their corresponding amide derivatives via the 1,2-C-to-N migrations. Recently, Fujioka and co-workers developed a train of NXS-induced oxidative rearrangements of secondary amines to afford a wide range of fused aliphatic N-heterocycles in good yields (Scheme 1a).3,6l In contrast to these NXS-promoted rearrangements,3,4 hypervalent iodine reagents have also frequently been used to accomplish a series of rearrangement reactions,5,6 due to their high electrophilicity and good leaving group capability.7 In spite Scheme 1. Halogen-Induced Rearrangement Reactions
Figure 1. Some examples of biologically active benzo-1,2,3-triazin4(3H)-ones.
4(3H)-ones can serve as pre-eminent building blocks to afford a range of valuable heterocycles through metal-catalyzed denitrogenative reactions.10 Traditionally, 1,2,3-benzotriazine4(3H)-ones are prepared from 2-aminobenzamide or methyl anthranilate via the diazotization using strong acid (HCl or H2SO4) and NaNO2 at 0 °C.11,12 Although this method arguably represents an effective strategy, it often suffers from narrow Received: September 3, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02813 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters substrate scope. In addition, this stepwise protocol for synthesis of benzotriazinones proceeds in an acidic condition. The substrates bearing acid-sensitive functional groups are not compatible with this transformation. As an alternative strategy, Liu and co-workers demonstrated a novel oxidative annulation of 2-aminobenzamides to access various N-substituted 1,2,3benzotriazine-4(3H)-ones using nitromethane as the nitrogen synthon.13 Although the targeted N-substituted 1,2,3-benzotriazine-4(3H)-ones could be obtained in good yields, acid (HOAc), high temperature (120 °C), and inert gas protection were prerequisite for this protocol. In 2016, the same group reported another efficient and mild TBAI-catalyzed synthesis of 1,2,3-benzotriazine-4-(3H)-ones from 2-aminobenzamides using tert-butyl nitrite as the nitrogen source.14 Later, Sankararaman developed a Pd-catalyzed annulation reaction of 1,3-diaryltriazenes to afford diverse 3-arylbenzo-1,2,3-triazin4(3H)-ones using CO as one carbon source in 2017.15 Despite these undisputed advances, some weaknesses in the known methods still remain to be addressed for the construction of 1,2,3-benzotriazine-4-(3H)-ones. The development of a new and mild route to assemble these significant benzotriazinones is still in demand. Herein, we disclose an expedient halo-mediated rearrangement reaction to forge these important 1,2,3benzotriazine-4-(3H)-ones starting from 3-aminoindazoles under mild conditions, which represents the first example of oxidative rearrangement of 3-aminoindazoles. To commence the study, commercial 1H-indazol-3-amine (1a) was chosen as a model substrate for screening of the reaction conditions. The initial experiment was conducted in the presence of N-bromosuccinimide (NBS) and ceric ammonium nitrate (CAN) at room temperature (Table 1, entry 1). A trace amount of the rearrangement product benzo[d][1,2,3]triazin4(3H)-one 2a was indeed detected by GC-MS. To our suprise, the yield of 2a was slightly increased to 17% when 0.1 mL of H2O was added to the reaction (Table 1, entry 2). Inspired by this result and the importance of H2O, we further screened the amount of water, and 0.5 mL of H2O was proven to be the best choice to afford the desired product 2a in 63% yield. We wondered if this transformation could be accomplished in water. However, when the model reaction proceeded in water without another solvent, only 22% yield of 2a was achieved (Table 1, entry 6). Subsequently, we investigated several common solvents. Only marginal improvements were obtained when other solvents were employed instead of CH3CN (Table 1, entries 7−9). We also inspected a number of oxidants (Table 1, entries 10−12). However, no superior results were gained. As part of a subsequent optimization, the model reaction was submitted to a series of bromide reagents to test the effects of different bromide sources (Table 1, entries 13−18). Among the bromide reagents investigated, 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) displayed the optimal one, furnishing the expected product 2a in 68% yield (Table 1, entry 15). With the optimal reaction conditions available, the scope and generality of this oxidative rearrangement of 3-aminoindazoles were assessed, which was summarized in Scheme 2. A range of functionalized 3-aminoindazoles having different electronic properties were proven to be good candidates to afford the desired 1,2,3-benzotriazine-4(3H)-ones (2b−2m) in decent yields. A suite of susceptive functional groups, such as chloro, bromo, iodo, ester, and nitro groups, were well compatible under this oxidative rearrangement reaction, which could provide an opportunity for further diversification to access various functionalized 1,2,3-benzotriazine-4(3H)-ones. To our delight,
Table 1. Optimization of Reaction Conditions
entrya
Br source
oxidant
solvent
yield of 2ab
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
NBS NBS NBS NBS NBS NBS NBS NBS NBS NBS NBS NBS TBAB NBP DBDMH DBA PTT LiBr
CAN CAN CAN CAN CAN CAN CAN CAN CAN K2S2O8 Na2S2O8 (NH4)2S2O8 CAN CAN CAN CAN CAN CAN
CH3CN CH3CN/H2O (10:1) CH3CN/H2O (3:1) CH3CN/H2O (2:1) CH3CN/H2O (1.25:1) H2O DCM/H2O (2:1) DCE/H2O (2:1) EtOAc/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1) CH3CN/H2O (2:1)
trace 17% 49% 63% 56% 22% 53% 38% 45% 41% 38% trace 58% 67% 68% 39% 55% trace
a Reaction and conditions: 1a (0.3 mmol), Br source (0.3 mmol), oxidant (0.45 mmol), CH3CN (1 mL), air, rt, 16 h. bIsolated yields.
the borneo-(−)-derived 3-aminoindazole 1n could also be engaged under the established conditions, enabling the production of 2n in 66% yield. In addition to monosubstituted 3-aminoindazoles, the disubstituted 3-aminoindazoles 1o and 1p were also found to react smoothly in this transformation, delivering the targeted products 2o and 2p in 75 and 68% yields, respectively. The scalability of this oxidative rearrangement reaction was also evaluated. When 3 mmol of 1a was submitted to this transformtion, the desired 1,2,3-benzotriazine-4(3H)-ones 2a could be readily obtained in 61% yield without loss of the efficacy (Scheme 3a). Further applications and transformations of this rearrangement product were also implemented. Treatment of 2a with propargyl bromide gave the 3-(prop-2-yn-1yl)benzo[d][1,2,3]triazin-4(3H)-one 3 in good yield under basic conditions. Very recently, our group developed a novel Cucatalyzed synthesis of 5-aryl-substituted 1,2,3-triazoles via an oxidative interrupted click reaction.16 We wondered if this benzotriazinone-derived terminal alkyne 3 could be engaged in this transformation. To our delight, this N-propargyl-substituted 1,2,3-benzotriazine-4(3H)-one 3 was amenable to this oxidative interrupted click reaction, rendering the desired 1,2,3-triazoles 4 in 88% yield. The 1,2,3-benzotriazine-4(3H)-ones 2a could also undergo the Cu-catalyzed Ullmann condensation of arylboronic acid17 to deliver the N-aryl-substituted 1,2,3-benzotriazine4(3H)-ones 5 in high yield, which could be utilized as versatile building blocks for the assembly of a series of N-heterocycles. For instance, 81% yield of isoquinolones 6 could be expediently obtained via the photoinduced denitrogenative alkyne insertion of 5.10h As noted in the literature,10c,d compound 5 was also B
DOI: 10.1021/acs.orglett.8b02813 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
underlying the identified conditions, 77% of 18O-labeled product 2a was detected (eq 1), which indicated that the oxygen of the carbonyl group should come from the water.
Scheme 2. Substrate Scope
On the basis of previous work,3,6l N-haloamines could be generated in situ in such halo-induced rearrangement reactions. However, 3-aminoindazoles have two types of N−H, both of which could undergo the halogenation. With this in mind, 1H NMR experiments were executed to confirm which N−H was halogenated first. When 1a reacted with DBDMH under the standard conditions for 25 min without CAN, the primary NH2 of 3-aminoindazoles disappeared. The signals of N-halogenated aminoindazoles were observed in the spectra (Figure 2b), which
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Reaction and conditions: 1 (0.3 mmol), DBDMH (0.3 mmol), CAN (0.45 mmol), MeCN/H2O = 2:1 (1.5 mL), air, rt, 16 h. aNBP (0.3 mmol). bCAN (0.6 mmol).
Figure 2. 1H NMR experiments.
Scheme 3. Synthetic Applications and Transformations showed that the primary NH2 of 3-aminoindazoles was preferentially halogenated under these oxidative conditions. Not surprisingly, the signals of 1,2,3-benzotriazine-4(3H)-ones 2a could be identified when 1a reacted with DBDMH and CAN at room temperature for 25 min (Figure 2c). Based on previous work and primary mechanism investigations, a plausible reaction mechanism of this oxidative rearrangement of 3-aminoindazoles is proposed in Scheme 4. First, 3-aminoindazole 1a reacts with the electrophilic bromide reagent, leading to the formation of N-haloaminoindazole A in situ, which undergoes an intramolecular nucleophilic attack to provide the active intermediate B. This incipient iminium intermediate B is further attacked by water to afford the intermediate C, which goes through the ring expansion process Scheme 4. Plausible Reaction Mechanism
reported to achieve the 3,4-dihydroisoquinolin-1(2H)-ones 7 and 3-(imino)isoindolin-1-ones 8 in excellent yields via the transition-metal-catalyzed denitrogenative annulation reactions. As a follow-up study, a sequence of experiments were performed to gain mechanistic insight into this oxidative rearrangement reaction. To clarify the origination of the carbonyl oxygen atom of the desired 1,2,3-benzotriazine4(3H)-ones, an isotope labeling experiment was carried out. When the reaction was conducted with 10 equiv of H218O C
DOI: 10.1021/acs.orglett.8b02813 Org. Lett. XXXX, XXX, XXX−XXX
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(6) For some examples of hypervalent iodine(III) reagent-induced migration rearrangement reactions, see: (a) Fujioka, H.; Komatsu, H.; Nakamura, T.; Miyoshi, A.; Hata, H.; Ganesh, J.; Murai, K.; Kita, Y. Chem. Commun. 2010, 46, 4133. (b) Jacquemot, G.; Canesi, S. J. Org. Chem. 2012, 77, 7588. (c) Farid, U.; Malmedy, F.; Claveau, R.; Albers, L.; Wirth, T. Angew. Chem., Int. Ed. 2013, 52, 7018. (d) Ahmad, A.; Scarassati, P.; Jalalian, N.; Olofsson, B.; Silva, L. F. Tetrahedron Lett. 2013, 54, 5818. (e) Liu, L.; Du, L.; Zhang-Negrerie, D.; Du, Y.; Zhao, K. Org. Lett. 2014, 16, 5772. (f) Shang, S.; Zhang-Negrerie, D.; Du, Y.; Zhao, K. Angew. Chem., Int. Ed. 2014, 53, 6216. (g) Yadagiri, D.; Anbarasan, P. Chem. Commun. 2015, 51, 14203. (h) Brown, M.; Kumar, R.; Rehbein, J.; Wirth, T. Chem. - Eur. J. 2016, 22, 4030. (i) Liu, L.; Zhang, T.; Yang, Y.-F.; Zhang-Negrerie, D.; Zhang, X.; Du, Y.; Wu, Y.D.; Zhao, K. J. Org. Chem. 2016, 81, 4058. (j) Malmedy, F.; Wirth, T. Chem. - Eur. J. 2016, 22, 16072. (k) Nakamura, A.; Tanaka, S.; Imamiya, A.; Takane, R.; Ohta, C.; Fujimura, K.; Maegawa, T.; Miki, Y. Org. Biomol. Chem. 2017, 15, 6702. (l) Murai, K.; Kobayashi, T.; Miyoshi, M.; Fujioka, H. Org. Lett. 2018, 20, 2333. (7) (a) Romero, R. M.; Wöste, T. H.; Muñiz, K. Chem. - Asian J. 2014, 9, 972. (b) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328. (8) (a) Palaniraja, J.; Roopan, S. M.; Rayalu, G. M. RSC Adv. 2016, 6, 24610. (b) Shinde, V. V.; Jeong, Y. T. Tetrahedron 2016, 72, 4377. (c) Shinde, V. V.; Jeong, Y. T. Tetrahedron Lett. 2016, 57, 3795. (d) Jadhav, A. M.; Balwe, S. G.; Lim, K. T.; Jeong, Y. T. Tetrahedron 2017, 73, 2806. (e) Li, L.; Xu, H.; Dai, L.; Xi, J.; Gao, L.; Rong, L. Tetrahedron 2017, 73, 5358. (f) Balwe, S. G.; Jeong, Y. T. Org. Chem. Front. 2018, 5, 1628. (g) Kong, W.; Zhou, Y.; Song, Q. Adv. Synth. Catal. 2018, 360, 1943. (h) Shinde, V. V.; Jeong, D.; Jung, S. J. Ind. Eng. Chem. 2018, DOI: 10.1016/j.jiec.2018.08.010. (9) (a) Wang, G.; Chen, X.; Deng, Y.; Li, Z.; Xu, X. J. Agric. Food Chem. 2015, 63, 6883. (b) Chang, Y.; Zhang, J.; Chen, X.; Li, Z.; Xu, X. Bioorg. Med. Chem. Lett. 2017, 27, 2641. (c) Zhang, F.; Wu, D.; Wang, G.; Hou, S.; Ou-Yang, P.; Huang, J.; Xu, X. Chin. Chem. Lett. 2017, 28, 1044. (10) (a) Miura, T.; Yamauchi, M.; Murakami, M. Org. Lett. 2008, 10, 3085. (b) Yamauchi, M.; Morimoto, M.; Miura, T.; Murakami, M. J. Am. Chem. Soc. 2010, 132, 54. (c) Miura, T.; Morimoto, M.; Yamauchi, M.; Murakami, M. J. Org. Chem. 2010, 75, 5359. (d) Miura, T.; Nishida, Y.; Morimoto, M.; Yamauchi, M.; Murakami, M. Org. Lett. 2011, 13, 1429. (e) Miura, T.; Yamauchi, M.; Kosaka, A.; Murakami, M. Angew. Chem., Int. Ed. 2010, 49, 4955. (f) Fang, Z.-J.; Zheng, S.-C.; Guo, Z.; Guo, J.-Y.; Tan, B.; Liu, X.-Y. Angew. Chem., Int. Ed. 2015, 54, 9528. (g) Wang, N.; Zheng, S.-C.; Zhang, L.-L.; Guo, Z.; Liu, X.-Y. ACS Catal. 2016, 6, 3496. (h) Wang, H.; Yu, S. Org. Lett. 2015, 17, 4272. (i) Thorat, V. H.; Upadhyay, N. S.; Murakami, M.; Cheng, C. H. Adv. Synth. Catal. 2018, 360, 284. (j) Hari Balakrishnan, M.; Sathriyan, K.; Mannathan, S. Org. Lett. 2018, 20, 3815. (11) (a) Van Heyningen, E. J. Am. Chem. Soc. 1955, 77, 6562. (b) Clark, A. S.; Deans, B.; Stevens, M. F. G.; Tisdale, M. J.; Wheelhouse, R. T.; Denny, B. J.; Hartley, J. A. J. Med. Chem. 1995, 38, 1493. (c) Colomer, J. P.; Moyano, E. L. Tetrahedron Lett. 2011, 52, 1561. (12) Barker, A. J.; Paterson, T. M.; Smalley, R. K.; Suschitzky, H. J. Chem. Soc., Perkin Trans. 1 1979, 1, 2203. (13) Yan, Y. Z.; Niu, B.; Xu, K.; Yu, J. H.; Zhi, H. H.; Liu, Y. Q. Adv. Synth. Catal. 2016, 358, 212. (14) Yan, Y.; Li, H.; Niu, B.; Zhu, C.; Chen, T.; Liu, Y. Tetrahedron Lett. 2016, 57, 4170. (15) Chandrasekhar, A.; Sankararaman, S. J. Org. Chem. 2017, 82, 11487. (16) Yu, X.; Xu, J.; Zhou, Y.; Song, Q. Org. Chem. Front. 2018, 5, 2463. (17) Sughara, M.; Ukita, T. Chem. Pharm. Bull. 1997, 45, 719.
to deliver the compound D. With the aid of an oxidant, compound D is oxidized to furnish the desired product 1,2,3benzotriazine-4(3H)-ones 2a. In conclusion, we have disclosed a novel oxidative rearrangement reaction of 3-aminoindazoles at room temperature. This newly discovered reactivity of 3-aminoindazoles enables the production of a range of functionalized 1,2,3-benzotriazine4(3H)-ones in good yields. The current protocol is characterized by features such as acid-free, no inert gas protection, simple operation, mild conditions, good yields, and a broad spectrum of functional group tolerance. In addition, this oxidative rearrangement reaction can be readily scaled up without loss of the efficacy. Further mechanism investigation and synthetic applications of this novel rearrangement reaction are in progress in our laboratory.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b02813. General experimental procedures and spectroscopic data for the corresponding products (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Yao Zhou: 0000-0002-3500-7355 Qiuling Song: 0000-0002-9836-8860 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Financial support from the National Natural Science Foundation of China (21202049), the Recruitment Program of Global Experts (1000 Talents Plan), the Natural Foundation of Fujian Province (2016J01064), Fujian Hundred Talents Plan, the Program of Innovative Research Team of Huaqiao University (Z14X0047), and Subsidized Project for Cultivating Postgraduates’ Innovative Ability in Scientific Research of Huaqiao University (for Y.Z.) is gratefully acknowledged. We also thank the Instrumental Analysis Center of Huaqiao University for analysis support.
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REFERENCES
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DOI: 10.1021/acs.orglett.8b02813 Org. Lett. XXXX, XXX, XXX−XXX
