A reiterative approach to 2,3-disubstituted naphthalenes and anthracenes

Article abstract of DOI:10.1021/ol991254w

(formula presented) Simple bis(bromoethynyl)arenediynes are easily prepared by the desilylative halogenation of the corresponding trimethylsilyl derivatives. Cycloaromatization of these halogenated enediynes leads to the otherwise difficult to prepare 2,3-dibromoarenes in good yield. Alkynylation of the resulting haloaromatic compound regenerates the soluble enediyne system, homologated by one aromatic ring. This iterative methodology can be terminated by the cycloaromatization of the unsubstituted enediyne, providing the simple acene hydrocarbon.

Full text of DOI:10.1021/ol991254w

ORGANIC
LETTERS
2000
Vol. 2, No. 1
85-87
A Reiterative Approach to
2,3-Disubstituted Naphthalenes and
Anthracenes
Daniel M. Bowles and John E. Anthony*
Department of Chemistry, UniVersity of Kentucky, Lexington, Kentucky 40506-0055
anthony@pop.uky.edu
Received November 17, 1999
ABSTRACT
Simple bis(bromoethynyl)arenediynes are easily prepared by the desilylative halogenation of the corresponding trimethylsilyl derivatives.
Cycloaromatization of these halogenated enediynes leads to the otherwise difficult to prepare 2,3-dibromoarenes in good yield. Alkynylation
of the resulting haloaromatic compound regenerates the soluble enediyne system, homologated by one aromatic ring. This iterative methodology
can be terminated by the cycloaromatization of the unsubstituted enediyne, providing the simple acene hydrocarbon.
Interest in the synthesis of acenes, the simplest class of
linearly-fused aromatic hydrocarbons, was initially spurred
by several reports that the corresponding polymer could be
an organic conductor.1 In the ensuing years, two distinct
routes to acenes have been reported: The first involves the
thermal treatment of highly conjugated prepolymers to yield
insoluble and difficult to characterize systems with some
promising electronic properties.2 The second route utilizes
Diels-Alder methodologies and has been most successful
for the preparation of cross-conjugated polyacenequinones
and partially saturated acene oligomers.3 The largest simple
acene prepared to date using this methodology is heptacene.
Recent reports that simple oligomeric acenes (such as
pentacene) can be used in the preparation of thin-film
transistors4 has rekindled interest in the synthesis of these
fused hydrocarbons, and we report here our initial investiga-
tions into an entirely new route to linearly fused aromatic
systems which utilizes a Bergman cycloaromatization reac-
tion,5 rather than Diels-Alder chemistry, in the ring-forming
step. Our initial application of this methodology in a
reiterative fashion allowed the rapid preparation of 2,3-
disubstituted naphthalene and anthracene in good yields.
Beginning with the easily prepared diyne 1,6 silver-
catalyzed desilylative bromination in acetone7 provided the
dibromide 2 (caution: mild lachrymator) in excellent yield.
This bis(bromoalkyne) decomposes rapidly when concen-
trated but is stable as a solution over a period of several
weeks, provided the material is kept in the dark.
Cycloaromatization of this halogenated compound simply
required heating a dilute (0.035 M) solution in a 10:1 (v/v)
(1) (a) Kivelson, S.; Chapman, O. L. Phys. ReV. B 1983, 28, 7236. (b)
Tanaka, K.; Ohzeki, K.; Nankai, S.; Yamabe, T.; Shirakawa, H. J. Phys.
Chem., Solids 1983, 44, 1069. (c) Kertesz, M.; Hoffmann, R. Solid State
Commun. 1983, 47, 97.
(2) (a) Minakata, T.; Imai, H.; Ozaki, M. Mol. Cryst. Liq. Cryst. 1993,
227, 231. (b) Kojima, Y.; Tsuji, M.; Matsuoka, T.; Takahashi, H.
Macromolecules 1994, 27, 3735.
(3) (a) Bailey, W. J.; Liaio, C.-W. J. Am. Chem. Soc. 1955, 77, 992. (b)
Ashton, P. R.; Brown, G. R.; Smith, D. R.; Stoddart, J. F.; Williams, D. J.
Tetrahedron Lett. 1993, 34, 8337. (e) Horn, T.; Wegener, S.; Mullen, K.
Macromol. Chem. Phys. 1995, 196, 2463. (f) Thomas, A. D.; Miller, L. L.
J. Org. Chem. 1986, 51, 4160.
(4) Dimitrakopoulos, C. D.; Purushothaman, S.; Kymissis, J.; Callegari,
A.; Shaw, J. M. Science 1999, 283, 822.
(5) (a) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25. (b) Lockhart, T.
P.; Comita, P. B.; Bergman, R. G. J. Am. Chem. Soc. 1981, 103, 4082.
(6) Takahashi, S.; Kuroyama, Y.; Sonagashira, K.; Hagihara, N. Synthesis
1980, 627.
(7) Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, R. Angew. Chem.,
Int. Ed. Engl. 1974, 23, 727.
10.1021/ol991254w CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/16/1999

benzene/1,4-cyclohexadiene (1,4-CHD) mixture to 180 °C
in a steel bomb for 2 h.8 After slow cooling to room
temperature, GC/MS analysis of the crude reaction mixture
showed 2,3-dibromonaphthalene 3 to be the only significant
product, contaminated by a small amount of 2-bromo-
naphthalene. A single recrystallization of this crude product
from heptane provided pure 2,3-dibromonaphthalene in 70%
yield. The efficiency with which 2 undergoes cycloaroma-
tization is unusual for an acyclic enediyne and might be
explained by the electron-withdrawing effects of the halo-
gens. Electron-withdrawing substituents have been shown
to accelerate the rate of other cycloaromatization reactions.9
In an attempt to avoid performing these cycloaromatization
reactions under pressure, we investigated a number of other
reaction conditions which utilized less-volatile hydrogen
atom sources. Our best results were obtained using in-
expensive γ-terpinene (bp 182 °C), which has been reported
to be a higher-boiling replacement for 1,4-cyclohexadiene
in cycloaromatization reactions10salthough for our systems
it proved to be significantly less efficient than 1,4-CHD.
Thus, when dibromide 2 was added slowly to a refluxing
(180 °C) solution of 1,2-dichlorobenzene/γ-terpinene (10:1
v/v) and allowed to react at that temperature overnight, we
were able to separate a 35% yield of dibromonaphthalene 3
from the significant amount of oligomerization and addition
products formed from this reaction.11 Increasing the propor-
tion of γ-terpinene did not improve the yield of the desired
product, and in fact when γ-terpinene was used as the
reaction solvent, the yield of dibromonaphthalene was
reduced dramatically. However, the ability to perform the
cycloaromatization in simple refluxing solvents, rather than
in a sealed pressure apparatus, is a significant advantage for
larger-scale reactions.
Scheme 1
A single attempt at performing a third iteration was
plagued with problems caused by the insolubility of the
intermediates (Scheme 2). The dibromide prepared by
Scheme 2
The alkynylation of 2,3-dibromonaphthalene was best
performed by palladium-catalyzed coupling with (trimeth-
ylsilylethynyl)zinc chloride in refluxing ether, which pro-
ceeded in significantly higher yield than any attempted
Sonagashira-type couplings.12 The overall yield for the first
full iteration (1 to 4) was 57%.
The second iteration was performed in a similar manner:
Desilylative bromination to form 2,3-bis(bromoethynyl)-
naphthalene and cycloaromatization at 180 °C followed by
alkynylation to give the desired bis(trimethylsilylethynyl)-
anthracene 5 in a 68% overall yield from 4 (Scheme 1). In
this case, we did not purify the intermediate dibromo-
anthracene before performing the acetylenic coupling, since
the very soluble 5 was significantly easier to separate from
the reaction byproducts.
desilylative halogenation of 5 was only sparingly soluble in
hot benzene, and the cycloaromatization of this material
produced a significant amount of black char. The palladium-
catalyzed coupling of (trimethylsilylethynyl)zinc chloride to
this crude material led to the recovery of approximately 20%
by mass of soluble material, which was a chromatographi-
cally inseparable mixture of products shown by GC/MS
analysis to include the desired diethynyl compound, the
monoethynyl compound, and several dehalogenated products.
It is obvious that the success of this iterative scheme depends
on the solubility of the intermediate dibromoenediyne.
The iterative process can be terminated in a number of
ways. For example, the dibromoarenes formed by cycloaro-
matization can be substituted with alkyl, aryl, or alkynyl
functional groups by well-known coupling chemistry.13 More
simply, the iterative process can be ended by the cyclo-
aromatization of the unsubstituted enediyne to yield the
(8) Lower temperature cycloaromatization runs were attempted, but led
to slow decomposition of starting material. All of the high-temperature
reactions performed in sealed systems were carried out behind protective
shielding.
(9) (a) Semmelhack, M. F.; Neu, T.; Foubelo, F. J. Org. Chem. 1994,
59, 5038. (b) Maier, M. E.; Greiner, B. Liebigs Ann. Chem. 1992, 855. (c)
Schmittel, M.; Kiau, S. Chem. Lett. 1995, 953.
(10) Grissom, J. W.; Calkins, T. L.; Egan, M. J. Am. Chem. Soc. 1993,
115, 11744.
(11) Addition of p-benzyne diradical to the hydrogen atom source is a
common byproduct of cycloaromatization reactions. See, e.g., ref 8a.
(12) (a) Negishi, E.; Kotora, M.; Xu, C. D. J. Org. Chem. 1997, 62,
8957. (b) John, J. A.; Tour, J. M. Tetrahedron 1997, 53, 15515.
86
Org. Lett., Vol. 2, No. 1, 2000

parent acene. Thus, anthracene 5 was desilylated with sodium
methoxide in THF to give the sparingly soluble diyne 7,
which was immediately subjected to cycloaromatization
conditions at 160 °C. Because of the moderate solubility of
free diyne 7 in hot benzene, the cycloaromatization reaction
proceeded with significantly less charring, producing a single
major compound. Recrystallization of the resulting crude
material three times from methylene chloride provided
naphthacene 8 in 64% yield.
In conclusion, we have demonstrated a simple cyclo-
aromatization-based methodology which was used in the
preparation of 2,3-dihalo- and 2,3-diethynylnaphthalene and
-anthracene. The yields for the process are good, and
purification is typically possible by simple recrystallization.
We have also shown that the terminal alkynes can undergo
cycloaromatization to give parent acenes, also in good yield.
Because the success of our iterative methodology appears
highly dependent on solubility of the intermediate dibro-
moenediyne, we are currently investigating the effect of
solubilizing groups on the cycloaromatization reaction. To
maximize the efficiency of the high-dilution cycloaromati-
zation reactions, we are also preparing systems with multiple
enediyne units to form large polycyclic systems in a single
step. The results of these investigations will be reported in
due course.
Acknowledgment. The authors gratefully acknowledge
support of this project from the Camille and Henry Dreyfus
Foundation (New Faculty Award to J.A.), Kentucky NSF-
EPSCoR program (EHR-91-08764 and DE-FG02-91-
ER75657), and the Office of Naval Research.
Supporting Information Available: Text giving experi-
mental procedures for the iterative process and spectroscopic
data for compounds 3, 4, 5, and 8. This material is available
free of charge via the Internet at http://pubs.acs.org.
(13) For example, nickel-catalyzed coupling with a Grignard reagent:
Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374-
4376.
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