Cascade reaction of 2,3-naphthalenediol with benzene in the presence of aluminum halides

Article abstract of DOI:10.1016/j.tetlet.2019.02.026

2,3-Naphthalenediol on superelectrophilic activation with aluminium halides smoothly reacts with benzene to give 4-((3-phenyl-1H-inden-1-yl)methyl)benzene-1,2-diol, which in turn undergoes intramolecular cyclization to form 5,10-methano-5-phenyldibenzo[a,d]cycloheptane-2,3-diol. The mechanistic aspects of these unusual transformations are discussed.

Full text of DOI:10.1016/j.tetlet.2019.02.026

Accepted Manuscript
Cascade reaction of 2,3-naphthalenediol with benzene in the presence of alu-
minum halides
Zhongwei Zhu, George E. Salnikov, Konstantin Yu. Koltunov
PII:
S0040-4039(19)30157-1
https://doi.org/10.1016/j.tetlet.2019.02.026
TETL 50620
DOI:
Reference:
Tetrahedron Letters
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11 February 2019
13 February 2019
Please cite this article as: Zhu, Z., Salnikov, G.E., Yu. Koltunov, K., Cascade reaction of 2,3-naphthalenediol with
benzene in the presence of aluminum halides, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.
2019.02.026
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Tetrahedron Letters
Cascade reaction of 2,3-naphthalenediol with benzene in the presence of aluminum
halides
Zhongwei Zhua, George E. Salnikova,b,c and Konstantin Yu. Koltunov*a,d
a Novosibirsk State University, Novosibirsk, 630090, Russian Federation
b N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
c International Tomography Center, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
d G. K. Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
2,3-Naphthalenediol on superelectrophilic activation with aluminium halides smoothly reacts
with benzene to give 4-((3-phenyl-1H-inden-1-yl)methyl)benzene-1,2-diol, which in turn
undergoes intramolecular cyclization to form 5,10-methano-5-phenyldibenzo[a,d]cycloheptane-
2,3-diol. The mechanistic aspects of these unusual transformations are discussed.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Naphthols
Superelectrophilic activation
Electrophilic aromatic substitution
Ionic reduction
1. Introduction
tetrahydronaphthalene-2,3-diol (5), which can rearrange further
into isomer 6 followed by dealkylation to pyrocatechol 7
It is known that 2-naphthol, 2,6- and 2,7-naphthalenediols
react with cyclohexane, benzene and other arenes in the presence
of an excess of aluminum halides to give corresponding 2-
tetralones (1) and 4-aryl-2-tetralones (2) through the key
intermediacy of dicationic superelectrophiles 3 (Scheme 1) [1].
In contrast, 2,3-naphthalenediol (4) reacts with cyclohexane on
its benzene moiety to afford exclusively 5,6,7,8-
(Scheme 1) [2]. However, the reactivity of diol 4 toward aromatic
compounds has not yet been studied, though the potential
reaction products could be of significant interest, taking into
account that catechols in general, and derivatives of 4 in
particular, are common structural motifs found in many bioactive
molecules and drugs [3]. Here, therefore, we present our findings
for the reaction of 4 with benzene.
Scheme 1. Known reactions of 2-naphthol, 2,3-, 2,6- and 2,7-naphthalenediols with cyclohexane and/or aromatics in the
presence of aluminum halides [1,2].

2
Tetrahedron
2. Results and discussion
the total reaction time for up to 170 and 48 h for the AlCl3 and
AlBr3 mediated reactions, respectively, electrophilic
Diol 4 was observed to react smoothly with benzene in the
intramolecular cyclization in 8 takes place to afford its derivative
9 in an overall yield of 60 to 65% (the range of isolated yields in
several experiments) (Scheme 2). It should be noted that attempts
to accelerate the reaction by increasing the temperature have
prompted mostly side reactions yielding, ultimately, compound 7.
The structures of 8 and 9 are determined unambiguously by
NMR (1D 1H and 13C, 2D COSY, NOESY, HSQC, HMBC) (see
the Supplementary).
presence of a 7 fold molar excess of AlCl3 at room temperature
for 72 h to form 4-((3-phenyl-1H-inden-1-yl)methyl)benzene-
1,2-diol (8) in about 60% isolated yield (Scheme 2). The same
reaction is mediated also by a 3 fold molar excess of AlBr3; the
complete consumption of 4 requires 24 h in that case [4].
Notably, the main byproducts of this reaction have proven to be
compounds 5-7 (1H NMR and GC-MS data). When increasing
Scheme 2. Reaction of diol 4 with benzene.
The proposed mechanism of the reaction is shown in Schemes
3 and 4. It involves O,C5-diprotonation/coordination of 4 leading
to generation of dicationic species 10, which is analogous to
O,C5-diprotonated form of 2-naphthol generated earlier along
with dications 3 (X = R1 = R2 = H) by dissolving 2-naphthol in
HF-SbF5-SO2ClF superacid system at −80 C [5]. The similar
activation of a benzene rather than phenolic moiety under
superacidic conditions is known to be more typical for N-
heterocyclic derivatives of 2-naphthol [6]. Next, ion 10 reacts
with benzene through electrophilic aromatic substitution to give
intermediate 11, which undergoes additional protonation and
reacts with the second molecule of benzene. Then, the
intermediate compound 12 rearranges into indane 13 as a result
of preliminary electrophilic aromatic dealkylation. However, the
would-be final reaction product 13 is not sufficiently stable under
reaction conditions due to its facile dehydrogenation to 8.
o
Scheme 3. A plausible mechanism for the formation of indene 8.
The latter step, namely hydrogen elimination, obviously
occurs via ionic hydrogenation of 4 with 13, which plays here the
same role as cyclohexane in the conversion 45 in Scheme 1, to
give, as expected, compound 8 along with byproducts 5-7 in a
molar ratio of ~2:1. It should be noted also that intermediate 10
may be additionally O-protonated/coordinated at the intact
hydroxyl group. This will increase electrophilicity of these
species even more. A catalytic amount of protic superacid
(HHal–AlnHal3n or H2O–AlnHal3n, Ho ≈ −18), which is required
for generation of 10 and subsequent electrophilic
transformations, is normally present in such reaction media due
to the in situ reaction between the excess of aluminium halides
and traces of water in the starting materials [7].
The mechanism of the transformation 89 is shown in
Scheme 4. In principle, generation of 9 could be accompanied by
the production of its isomer 14. However, that reaction pathway
seems to be restricted by the unfavorable peri interaction [8].
Scheme 4. Mechanism of formation of 9.

Koltunov, A. N. Chernov, G. K. S. Prakash, G. A. Olah, Chem.
Pharm. Bull. 2012, 60, 722–727; (d) K. Yu. Koltunov, A. N.
Chernov, L. A. Ostashevskaya, P. A. Gribov, Mendeleev Commun.
2014, 24, 122–124; (e) K. Yu. Koltunov, L. A. Ostashevskaya, I.
B. Repinskaya, Russ. J. Org. Chem. 1998, 34, 1796–1797; (f) L.
A. Ostashevskaya, K. Yu. Koltunov, I. B. Repinskaya, Russ. J.
Org. Chem. 2000, 36, 1474–1477; (g) G. A. Olah, D. A. Klumpp,
In Superelectrophiles and Their Chemistry, Wiley: New York,
2008.
Conclusion
In summary, the found behaviour of 4 under the influence of
excess aluminium halides can plausibly be interpreted in terms of
key O,C-diprotonated/coordinated superelectrophilic
intermediates, such as species 10. Diol 4 reacts with benzene
similarly to its reaction with cyclohexane, on benzene moiety of
the molecule [2]. However, the reaction is complemented by
further sequence of facile electrophilic transformations leading to
the formation of polycyclic compound 9. The latter is close
structural analogue of 5-phenyl-5,6,7,8-tetrahydronaphthalene-
2,3-diol, one of the promising therapeutic agents for breast cancer
[3b], and it might therefore be of interest to clinical trials.
2. Z. Zhu, L. A. Ostashevskaya, K. Yu. Koltunov, Tetrahedron Lett.
2015, 56, 2254–2257.
3. (a) M. Monier, A. El-Mekabaty, D. Abdel-Latif, K. M.
Elattar, Synth. Commun. 2018, 48, 2305–2332; (b) J. E. Blecha,
M. O. Anderson, J. M. Chow, C. C. Guevarra, C. Pender, C.
Penaranda, M. Zavodovskaya, J. F. Youngren, C. E. Berkman,
Bioorg. Med. Chem. Lett. 2007, 17, 4026–4029; (c) C. Huang, N.
Ghavtadze, B. Chattopadhyay, V. Gevorgyan, J. Am. Chem. Soc.
2011, 133, 17630–17633, and references cited therein.
Acknowledgments
4. It should be noted that a 3–7 fold molar excess of aluminum halide
is not essential and a decrease in the loading is possible. This,
however, slows down the reaction, and the use of less than a 2-
fold molar excess of AlHal3 completely suppresses it.
5. I. B. Repinskaya, K. Yu. Koltunov, M. M. Shakirov, V. A.
Koptyug, J. Org. Chem. USSR 1992, 28, 785–795.
6. (a) K. Yu. Koltunov, G. K. S. Prakash, G. Rasul, G. A. Olah, J.
Org. Chem. 2002, 67, 8943–8951; (b) K. Yu. Koltunov, G. K. S.
Prakash, G. Rasul, G. A. Olah, Heterocycles 2004, 62, 757–772.
7. (a) G. A. Olah, G. K. S. Prakash, A. Molnar, J. Sommer. In
Superacid Chemistry, Wiley, New York, 2nd edn, 2009; (b) G. P.
Smith, A. S. Dworkin, R. M. Pagni, S. P. Zingg, J. Am. Chem.
Soc. 1989, 111, 525–530; (c) G. P. Smith, A. S. Dworkin, R. M.
Pagni, S. P. Zingg, J. Am. Chem. Soc. 1989, 111, 5075–5077; (d)
M. N. Vo, Y. Basdogan, B. S. Derksen, N. Proust, G. A. Cox, C.
Kowall, J. A. Keith, J. K. Johnson, ACS Catal. 2018, 8,
8006−8013.
This work was conducted within the framework of the budget
project #АААА-А17-117041710083-5 for Boreskov Institute of
Catalysis. We also acknowledge the Multi-Access Chemical
Research Center of the Siberian Branch of the Russian Academy
of Sciences for the spectral measurements.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org...
References and notes
8. V. Balasubramaniyan, Chem. Rev. 1966, 66, 567–641.
1. (a) K. Yu. Koltunov, I. B. Repinskaya, M. M. Shakirov, L. N.
Shchegoleva, Russ. J. Org. Chem. 1994, 39, 88–96; (b) K. Yu.
Koltunov, Tetrahedron Lett. 2008, 49, 3891–3894; (c) K. Yu.

4
Tetrahedron
Highlights
 2,3-Naphthalenediol undergoes
superelectrophilic activation in the presence
of AlCl3 or AlBr3
 This provides its cascade reaction with
benzene at mild conditions
 The intermediate reaction product is 4-((3-
phenyl-1H-inden-1-yl)methyl)benzene-1,2-
diol
 The final reaction product is 5,10-methano-
5-phenyldibenzo[a,d]cycloheptane-2,3-diol
 The last compound can be of interest to
clinical trials as anti-breast cancer agent

Cascade reaction of 2,3-naphthalenediol with
benzene in the presence of aluminum halides
Leave this area blank for abstract info.
Zhongwei Zhu, George E. Salnikov and Konstantin Yu. Koltunov*