Aromatization of highly alkyl-substituted dihydroanthracenes using n-BuLi/TMEDA/MeI

Article abstract of DOI:10.1246/cl.2001.646

Aromatization of highly alkyl-substituted dihydroanthracene was performed with the n-BuLi/TMEDA/MeI. Treatment of 1,2,3,4,5,6,7,8-octapropyl-9, 10-dihydroanthracene with 2.2 equiv of n-BuLi, TMEDA at 50 °C in hexane for 3 h, followed by 1.1 equiv of MeI at room temperature for 1 h gave the corresponding anthracene in 98% yield.

Full text of DOI:10.1246/cl.2001.646

6
46
Chemistry Letters 2001
Aromatization of Highly Alkyl-substituted Dihydroanthracenes
Using n-BuLi/TMEDA/MeI
Masanori Kitamura, Baojian Shen, Yanjun Liu, Hegen Zheng, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University
and CREST, Science and Technology Corporation (JST), Sapporo 060-0811
(Received, March 26, 2001; CL-010276)
Aromatization of highly alkyl-substituted dihydroanthracene
was performed with the n-BuLi/TMEDA/MeI. Treatment of
,2,3,4,5,6,7,8-octapropyl-9,10-dihydroanthracene with 2.2 equiv
of n-BuLi, TMEDA at 50 °C in hexane for 3 h, followed by 1.1
equiv of MeI at room temperature for 1 h gave the corresponding
anthracene in 98% yield.
chromatography was not necessary in this case.
The n-BuLi/TMEDA/MeI is effective for, in particular,
highly alkyl-substituted dihydroanthracenes. As shown in Table
1, non-substituted 9,10-dihydroanthracenes gave only 47% and
less than 5% of anthracene when treated in this system with MeI
and MeBr, respectively. However, octapropyl- or octaethyl-
dihydroanthracene, or even 1,2,3,4-tetrapropyl-9,10-dihydro-
anthracene was converted into the corresponding anthracenes in
excellent yields using the n-BuLi/TMEDA/MeI system. It is
obvious that alkyl substituents restrained the methylation with
MeI but promoted aromatization by steric factor.
1
Recently, we have reported novel method for the synthesis
of highly substituted naphthacenes or pentacenes by homologa-
1
2
tion and highly alkyl-substituted benzene derivatives, naph-
3
thalenes or anthracenes. Introduction of substituents in poly-
cyclic compounds has been important to improve their solubility
4
and change their properties. During the course of our study, we
found novel aromatization reaction using n-BuLi (2.2
equiv)/TMEDA/MeI(1.1 equiv) for the highly alkyl-substituted
dihydroanthracenes.
Harvey and his coworkers reported that the treatment of 9,
1
0-dihydrophenanthrene with 3 equiv of RLi, TMEDA, and
MeBr afforded 94% of phenanthrene as a sole product and they
5
reported that this aromatization proceeded via electron transfer.
To the contrary, it was reported that treatment of dihydroan-
thracene with n-BuLi/TMEDA/MeBr gave a methylation prod-
5
uct, 9-methyl-9,10-dihydroanthracene, but not the aromatization
product. In addition, it is also known that a reaction of 9-iso-
propyl-9,10-dihydroanthracene with n-BuLi/TMEDA/excess
5a
MeI afforded only the methylation product.
In this paper, we would like to report that highly alkyl sub-
stituted dihydroanthracene reacted with n-BuLi (2.2
equiv)/TMEDA/MeI (1.1 equiv) in this order to give
anthracenes in high yields as shown in eq 1. In particular, only
1
.1 equiv of MeI was required in this aromatization which is in
5
sharp contrast to the method via electron transfer.
Typical procedure is as follows. To a hexane solution of
1
,2,3,4,5,6,7,8-octapropyl-9,10-dihydroanthracene 1 (R = Pr)
were added 2.2 equiv of n-BuLi and 2.2 equiv of TMEDA at
room temperature and the mixture was stirred at 50 °C for 3 h
Various kinds of combination of RM/R'X were investigat-
ed for the aromatization of 1. The results were summarized in
Table 2. As for R'X, MeI was the best. PrI or BuBr gave low
yield of the product. As for RM, sec-BuLi, tert-BuLi, PhLi
showed excellent yields of 2. Grignard reagent did not give the
product.
under N . Treatment of the mixture with 1.1 equiv of MeI at
2
6
room temperature for 1 h afforded 2 in 98% NMR yield. The
mixture was washed with 3M HCl. Its organic layer was dried
and evaporated to remove all volatile compounds. Pure com-
pound 2 was obtained in 96% yield. Purification using column
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
647
high reaction temperature. CdCl is not desirable from the point
2
of view of circumstances. DDQ can be used under mild condi-
7
tions. However, DDQ reacted with the aromatization product.
In fact, aromatization of 1 (R = Pr) using 1.1 equiv of DDQ at
room temperature afforded a mixture of the desired compound
8
2
(R = Pr) and the Diels-Alder product in 49% and 30% yields,
respectively, after 1 h, although control of the amount of DDQ
or reaction temperature can improve the yield of 2.
The novel aromatization system, n-BuLi/TMEDA/MeI, has
the following advantage. (i) High reaction temperature is not
required; (ii) excellent yield is achieved within several hours for
highly alkyl substituted anthracenes; (iii) easy work-up affords
very pure products.
Further investigation is in progress in the area of highly
substituted aromatic compounds.
It is also noteworthy that only 1 equiv of MeI is required as
shown in Figure 1. This clearly showed that this aromatization
system is different from the conventional electron transfer
reaction. A novel aromatization mechanism for our reaction is
proposed in Scheme 1. It involves i) the formation of a dianion
of the dihydroanthracene, ii) monoiodination of the dianion
with one equiv of MeI, and iii) elimination of lithium iodide
giving highly substituted anthracenes. Monoiodination with
one equiv of MeI produces MeLi. In fact, addition of benzalde-
hyde to the reaction mixture gave 1-phenylethyl alcohol.
References and Notes
1
T. Takahashi, M. Kitamura, B. Shen, and K. Nakajima, J.
Am. Chem. Soc., 122, 12876, (2000).
2
a) T. Takahashi, F.-Y. Tsai, Y. Li, K. Nakajima, and M.
Kotora, J. Am. Chem. Soc., 121, 11093 (1999). b) T.
Takahashi, Z. Xi, Yamazaki, A. Y. Liu, K. Nakajima, and M.
Kotora, J. Am. Chem. Soc., 120, 1672 (1998). c)T.
Takahashi, M. Kotora, and Z. Xi, J. Chem. Soc., Chem.
Commun., 1995, 361.
Compared with various conventional aromatization
3
4
T. Takahashi, R. Hara, Y.Nishihara, and M. Kotora, J. Am.
Chem. Soc., 118, 5154 (1996).
reagents5c such as Pd/C, n-BuLi/CdCl , and DDQ, our novel
2
aromatization system has some advantage. Pd/C requires very
For a review on alkylation of aromatic compounds, see a) F.
M. Menger, Top. Curr. Chem., 136, 1 (1986). b) G. A. Olah,
R. Krishnamurti, and G. K. S. Prakash in "Comprehensive
Organic Synthesis," ed by B. M. Trost and I. Fleming,
Pergamon Press Ltd., Oxford (1991), Vol. 3, p. 293.
a) R. G. Harvey, L. Nazareno, and H. Cho, J. Am. Chem.
Soc., 95, 2377 (1973). b) R. G. Harvey and H. Cho, J. Am.
Chem. Soc., 96, 2434 (1974). c) P. P. Fu and R. G. Harvey,
Chem. Rev., 78, 317 (1978).
5
6
7
8
NMR yields were calculated using mesitylene as an internal
standard.
A. Matsuura, T. Nishinaga, and K. Komatsu, Tetrahedron
Lett., 38, 3427 (1997).
1
H NMR (CDCl , Me Si) δ 1.02 (t, J = 7.2 Hz, 6H), 1.05 (t, J
3
4
=
7.2 Hz, 6H), 1.13 (t, J = 7.2 Hz, 6H), 1.20 (t, J = 7.2 Hz,
6
1
H), 1.26–1.54 (m, 14H), 1.85–1.96 (m, 2H), 2.35–2.63 (m,
2H), 2.66-2.87 (m, 4H), 5.46 (s, 2H); 13C NMR (CDCl3,
Me Si) δ 14.88, 14.93, 15.13, 24.66, 24.83, 24.86, 25.02,
4
3
1
1.16, 31.63, 31.92, 49.55, 56.76, 114.77, 131.40, 132.58,
35.65, 135.90, 139.91, 140.51, 143.61, 179.43.