Facile C?H alkylation in water: Enabling defect-free materials for optoelectronic devices

Article abstract of DOI:10.1021/jo100028d

A facile method for the alkylation of fluorene achieved via direct C?H alkylation under aqueous conditions is reported, wherein the formation of fluorenone is inhibited, resulting in the exclusive formation of the desired dialkyl-substituted fluorene monomer. As a proof of concept, this method has also been successfully extended to perform N-alkylation of carbazole, diphenylamine, and N,N-dialkylation of aniline in high yields.

Full text of DOI:10.1021/jo100028d

pubs.acs.org/joc
more intense in electroluminescence (EL) than in photolumi-
Facile C-H Alkylation in Water: Enabling
Defect-Free Materials for Optoelectronic Devices
3
nescence (PL). Numerous papers attribute this band to the
formation of emissive fluorenone units in the polymer back-
4
bone that intensifies with increasing fluorenone concentra-
Gunin Saikia and Parameswar K. Iyer*
tion. Thus, under all circumstances, the 9-position hydrogens
in fluorene are the sole culprits that undergo oxidation to form
fluorenone units when subjected to high thermal conditions
during device fabrication or photo-degradation when exposed
to light. Hence, finding an appropriate and facile method for
the preparation of “defect free” alkyl-substituted fluorene
monomers not only remains a challenge but would also be a
striking achievement to produce stabilized blue light emitting
devices.
Department of Chemistry, Indian Institute of Technology,
Guwahati 781039, Assam, India
pki@iitg.ernet.in
Received January 13, 2010
A common practice associated with C9 alkylation reactions
of fluorene reported so far utilizes high-boiling solvents such as
5-10
DMSO, DMF, HMPA, etc. as the reaction medium.
Yields obtained by these methods were in the range of 63-
0%. DMSO, a solvent used very often, has several draw-
8
backs, most prominently its environmentally adverse impact
and second the tedious reaction workup for the sepa-
ration of DMSO from the final product. Few other alkylation
methods reported in the literature have utilized a combination
of different solvents with metal catalysts, phase-transfer cata-
lysts (PTCs), very strong bases, multiple synthetic steps, and
7-10
extreme reaction conditions,
yet the art of making defect-
free dialkylated fluorene has not been achieved. Employing the
above routes affects the overall economy of the reaction and
needs extraordinary precautions and specialized conditions for
obtaining defect-free dialkylated product. This encouraged us
to investigate a simpler route for the dialkylation of fluorene
that would be economical, environmental friendly, and high
yielding in contrast to the existing methods. The reactivity of
the C-H bond present at the 9-position of “unsubstituted
fluorene” is extremely poor compared to the fluorene molecule
having electron-withdrawing halogen substituents at the 2,7-
positions or only at the 2-position. Hence, activation of the
C-H bond in “unsubstituted fluorene” is predominantly
challenging owing to which this compound has been avoided
or overlooked for alkylation reactions. In this paper, we
demonstrate that alkylation of “unsubstituted fluorene” can
be performed by means of an uncomplicated and facile route,
allowing insertion of a wide variety of alkyl chains on the
A facile method for the alkylation of fluorene achieved
via direct C-H alkylation under aqueous conditions is
reported, wherein the formation of fluorenone is inhib-
ited, resulting in the exclusive formation of the desired
dialkyl-substituted fluorene monomer. As a proof of
concept, this method has also been successfully extended
to perform N-alkylation of carbazole, diphenylamine,
and N,N-dialkylation of aniline in high yields.
Polydialkylfluorenes possess excellent photophysical, ther-
mal, and processing properties, which have made them one of
the most promising materials presently being used to fabricate
blue-light emitting diodes (LEDs) and biosensor applica-
1,2
tions. The presence of a rigidly planar biphenyl unit with a
methylene bridge allows functionalization at the 9-position
resulting in high solubility and processability in the resulting
polymers. However, several studies have demonstrated that
poly(9,9-dialkylfluorene) degrades to give a longer wavelength
emission band in the presence of oxygen over time which is
9-position of fluorene in exceptional yields. Importantly, we
establish that this alkylation route could be extended to
(
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714 J. Org. Chem. 2010, 75, 2714–2717
Published on Web 03/18/2010
DOI: 10.1021/jo100028d
r 2010 American Chemical Society

Saikia and Iyer
JOCNote
SCHEME 1. General Synthetic Scheme for Synthesis of Un-
substituted 9,9-Dialkylfluorene
TABLE 1. Yields Obtained for Alkylation of Fluorene with Ten Dif-
ferent Alkyl Halides in Aqueous NaOH, TBAI as PTC at 70 °C
a
a
R-X = alkyl halide.
several other important intermediates and precursors for, e.
g., dialkylation of substituted and partially substituted
fluorene, N-alkylation of carbazole and diphenylamine,
and N,N-dialkylation of aniline, all of which are vital as
charge-transporting and luminescent materials for optoelec-
tronic devices and sensors. While working on this challenge,
we emphasized on the use of reagents and reaction condi-
tions that are economical, safe, and lead to high-yielding
products.
Initial attempts to perform dialkylation on “unsubstituted
fluorene” in the presence of excess haloalkane (up to 20
times), aq NaOH, and tetrabutylammonium iodide (TBAI)
in DMSO and/or water at elevated temperatures yielded
fluorenone as the sole product, which made us realize that
the art of making dialkylated fluorene is not so straightfor-
ward as perceived and one of the prime reasons for “unsub-
stituted fluorene” to be overlooked. Several repetitions of the
reaction under varying conditions confirmed that the fore-
most problem in these reactions is trace amounts of oxygen,
which was found to be so reactive that in the presence of base,
fluorenone was formed as the exclusive product even at
temperatures of 35-50 °C. Fluorenone formation can be
easily visualized by the distinct yellow color of the isolated
product and from the 1720 cm ketone peak in the IR data.
This trace oxygen has either been ignored or considered to be
very trivial while performing the fluorene dialkylation reactions;
nonetheless, it is the most perilous condition in obtaining
defect-free dialkylated fluorene to be used as interme-
diates and precursors for numerous applications in foresee-
able future. After several failed attempts, modifications were
made in the reaction (Scheme-1) so as to obtain the desired
dialkylated product in 85-98% yields. (Table-1) To the best
of our knowledge, there are no literature reports wherein
difunctionalization of alkanes, more specifically “unsubsti-
tuted fluorene”, has been successfully performed with a
series of haloalkanes in the absence of metal catalysts, or-
ganic solvents, inert gases, and high pressure/temperature to
obtain desired dialkylation products in high yields as re-
ported here.
yields of up to 98% (entry 1b) have been obtained on reacting
fluorene with 1-bromooctane. Similarly, highly dialkylated
fluorene yields were also obtained by the reaction of fluorene
with 1-bromohexane (96%), 1-bromoundecane (88%), 2-ethyl-
hexyl bromide (88%), 1,6-dibromohexane (95%), and 1,8-
dibromooctane (90%) (entries 1a, 1c-f). Reaction of fluorene
with 1,6-diiodohexane (90%) and 1,8-iodooctane (88%)
(
entries 1g,h) also gave highly dialkylated product yields,
whereas less reactive chloroalkanes, i.e., 1-chlorohexane and
-chlorooctane, when treated with fluorene gave decent yields
1
of 85% and 87% (entries 1i,j) within 7 h under the same
conditions, proving the versatility of this reaction for a wide
variety of substrates having diverse structure and less reactivity.
Since the reaction is performed in aqueous medium the separa-
tion of the desired dialkylated product was also very straight-
forward. All the dialkylated products obtained were well
-
1
1
13
characterized by FT-IR, H NMR, C NMR, and mass
spectroscopy and confirmed to be free from fluorenone
(Supporting Information).
Aqueous NaOH was used as a base in the above-described
alkylation reaction that facilitated the synthesis of desired
dialkylated fluorene in high yields. To ensure that dialkyla-
tion of fluorene proceeds smoothly, excess alkyl halide is
used in these reactions. It is important that all the fluorene
monomers get dialkylated before being exposed to oxygen,
since any monoalkylated fluorene remaining in the reaction
can still form fluorenone in the presence of oxygen during
1
1
device fabrication. As discussed earlier, besides the role of
base and PTC in the alkylation of fluorene, it is important to
ensure that no oxygen is present in these reactions because
the fluorene would react with this oxygen to generate un-
desiredfluorenone. SincetheconditionsreportedinScheme1
are easy and strikingly efficient, we expect this simple
alkylation reaction to be of prime interest to the synthetic
community and materials scientists to develop defect-free
polyfluorene derivatives.
Fluorene was reacted with a range of alkyl halides that
include chloro-, bromo-, and iodo-terminated hydrocar-
bons (Scheme-1) at moderate temperature of 70 °C in the
presence of 50% aq NaOH and TBAI to obtain the desired
dialkylated products in high yields (Table-1). Before the
addition of alkyl halide into the reaction mixture, the
complete removal of oxygen via repeated freeze-thaw
degassing cycles of 15 min each (alternatively warming
to room temperature) was performed to remove undesired
oxygen gas. Bromoalkanes, due to their economy and
better reactivity, have been extensively used for alkylation
of fluorene. We have chosen six different types of bro-
moalkanes that include long-chain, branched-chain, and
dibromo-substituted-chain derivatives. Exceptionally high
Furthermore, we observed that the PTC has a prominent
role in facilitating the dialkylation reaction, in addition to other
favorable conditions required to achieve the dialkylated
(11) Gong, X.; Iyer, P. K.; Moses, D.; Xiao, S. S.; Bazan, G. C.; Heeger,
A. J. Adv. Funct. Mater. 2003, 4, 325–330.
J. Org. Chem. Vol. 75, No. 8, 2010 2715

Saikia and Iyer
JOCNote
TABLE 2. Comparative Reactivity Study of Fluorene Dialkylation by
TABLE 3. Optimizing the Accurate Quantity of PTC Required for
Obtaining Maximum Dialkylated Fluorene
1
-Bromohexane in the Presence of Various PTCs in Water at 70 °C
isolated
time (h) yield (%)
entry no.
TBAI quantity
time (h)
isolated yield (%)
entry no.
phase-transfer catalyst (PTC)
3
a
0.01 g (2.5 mol %)
0.02 g (5 mol %)
0.03 g (7.5 mol %)
0.046 g (10 mol %)
0.1 g (25 mol %)
0.5 g (>100 mol %)
10
10
10
6
6
6
50
75
82
98
98
98
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
tetrabutylammonium iodide(TBAI)
tetrabutylammonium bromide(TBAB)
tetrabutylammonium chloride(TBAC)
tetrabutylammonium fluoride (TBAF)
tetraethylammonium iodide (TEAI)
tetraethylammonium bromide (TEAB)
tetraethylammonium chloride (TEAC)
15-crown-5
4
8
8
12
8
10
12
12
12
24
96
90
60
50
90
85
50
30
15
12
3b
3c
3d
3e
3f
TABLE 4. Alkylation of Different Substrates in Water at 70 °C with
sodium dodecyl sulfate (SDS)
without PTC
a
1
-Bromohexane
j
products. Table 2 represents a comparative reactivity study
of the dialkylation of fluorene by 1-bromohexane in the
presence of several PTCs at 70 °C. TBAI showed the best
performance (entry 2a) both in terms of facilitating higher
dialkylated product yields and lesser reaction time compared
to all other PTCs examined here. These include tetrabuty-
lammonium bromide (TBAB), tetrabutylammonium chloride
(
TBAC), tetrabutylammonium fluoride (TBAF), tetra-
ethylammonium iodide (TEAI), tetraethylammonium bromide
TEAB), tetraethylammonium chloride (TEAC), 15-crown-5,
(
sodium dodecyl sulfate (SDS), etc. As observed in Table 2,
the product yield is best when performed in the presence of
TBAI, followed by TBAB and TEAI (entries 2b and 2e)
closely followed by TEAB (entry 2f). A general trend ob-
served in these reactions indicated that the iodide-containing
PTC were most efficient (entries 2a and 2e) compared to
bromide (entries 2b and 2f), chloride (entries 2c and 2g), and
fluoride (entry 2d) both in terms of shorter time durations
and higher yields. 15-crown-5 and SDS showed little or no
effect on the product yields (entries 2h and 2i). Alkylation
performed in the absence of PTC gave very poor product
yield in 24 h (entry 2j), validating the use of appropriate PTC
in these reactions. Since TBAI is one of the cheapest and
most easily available PTCs, its application benefits the over-
all economy of the alkylation reactions.
a
6 13
R = C H .
9
1%, 75%, and 72% obtained for carbazole, diphenylamine,
and aniline (Table 4, entries 4c-e) confirm that this facile
and economical method is very efficient for the N-alkylation
of primary and secondary amines (in addition to C-
alkylation) that have been extensively applied in optoelec-
tronic devices as emitting/transporting materials, sensors,
1
2-14
and dopants.
This method represents the first example
of aqueous N-alkylation reaction performed with such high
efficiency in the absence of metal catalyst, organic solvent,
and moderate reaction conditions on this important class of
materials with a scope of extension to other challenging
N-substitution reaction.
After establishing that TBAI is the best PTC, we investi-
gated its accurate quantity required for the best product
yields. Table 3 depicts that 10 mol % of TBAI was sufficient
for successful conversion of fluorene to dialkylated fluorene
(entry 3d). Adding greater than 10 mol % of TBAI did not
In summary, we have established a simple and economical
methodology for the alkylation of fluorene (unsubstituted
and substituted) and N-alkylation reactions in aqueous med-
ium whose efficiency is much higher than that of currently
applied methods. In view of the fact that these reactions are
fundamental in organic synthesis and very critical for the
enhance the yields of dialkylated products (entries 3e and 3f).
However, decreasing the amount of TBAI below 10 mol %
reduced the yield as well as prolonged the reaction time
(entries 3a-c). As part of our objective to bring simpler
synthetic routes into the realm of “materials”, the above-
developed alkylation method was extended to other impor-
tant substrates and reactions to authenticate this synthetic
route for broader applications. Using the same conditions as
above (Supporting Information), 2,7-dibromofluorene
(
12) (a) Peng, Z.; Bao, Z.; Yu, L. J. Am. Chem. Soc. 1994, 116, 6003–6004.
b) Kuo, W.-J.; Hsiue, G.-H.; Jeng, R.-J. Macromolecules 2001, 34, 2373–
384. (c) Liu, S.; Jiang, X.; Ma, H.; Liu, M. S.; Jen, A. K. Y. Macromolecules
(
2
(
entry 4a) and 2-bromofluorene (entry 4b) were dialkylated
2000, 33, 3514–3517. (d) Huang, Q.; Evmenenko, G.; Dutta, P.; Marks, T. J.
J. Am. Chem. Soc. 2003, 125, 14704–14705.
in outstanding yields of 99% and 98% with 1-bromohexane
in a shorter time duration than existing methods. Most
notably, there was no fluorenone formation along with any
of the final products, confirmed by TLC as well as the
(13) (a) Cho, J.-S.; Kimoto, A.; Higuchi, M.; Yamamoto, K. Macromol.
Chem. Phys. 2005, 206, 635–641. (b) Chi, C.-C.; Chiang, C.-L.; Liu, S.-W.;
Yueh, H.; Chen, C.-T.; Chen, C.-T. J. Mater. Chem. 2009, 19, 5561–5571.
(14) (a) Brunner, K.; Dijken, A. V.; Boerner, H.; Bastiaansen, J. J. A. M.;
Kiggen, N. M. M.; Langeveld, B. M. W. J. Am. Chem. Soc. 2004, 126, 6035–
6042. (b) Thomas, K. R. J.; Velusamy, M.; Lin, J. T.; Chuen, C.-H.; Tao, Y.-T.
Chem. Mater. 2005, 17, 1860–1866. (c) You, Y.; Kim, S. H.; Jung, H. K.;
Park, S. Y. Macromolecules 2006, 39, 349–356. (d) Tao, Y.; Wang, Q.; Yang,
C.; Wang, Q.; Zhang, Z.; Zou, T.; Qin, J.; Ma, D. Angew. Chem., Int. Ed.
2008, 47, 8104–8107.
-
1
absence of ∼1720 cm ketone peak in IR data.
Furthermore, this alkylation method has been successfully
extended to perform N-alkylation of carbazole, diphenyla-
mine, and N,N-dialkylation of aniline. The high yields of
2
716 J. Org. Chem. Vol. 75, No. 8, 2010

Saikia and Iyer
JOCNote
development of defect free polymeric materials, this metho-
dology offers advantages not just for fluorene alkylation
reactions but also to a variety of N-alkylations. As a proof
of concept, we utilized this reaction for the alkylation of
primary and secondary aromatic amines, offering a wide
variety of potential applications in peptide synthesis. We are
presently making efforts to extend this reaction procedure for
various other classes of substrates and chemoselective synth-
esis. Since our protocol proceeds under purely aqueous con-
ditions, utilizes readily available, inexpensive, stable, and
nontoxic chemicals and avoids use of metal catalyst, this
method is very facile, economical, and environmentally benign
and could be applied to wide-ranging alkylation reactions.
by applying freeze-thaw cycles. 2-Ethylhexyl bromide (1.70 g,
8.82 mmol) was added via syringe (degassed) and the mixture
heated at 70 °C continuously for 4 h. The reaction mixture was
cooled to room temperature and extracted with chloroform. The
organic layer was washed with water and dried over anhydrous
sodium sulfate. The solvent was removed under vacuum, and
the crude was purified via column chromatography over a small
pad of silica gel with 10% chloroform in hexane as the eluent to
give the desired dialkylated product. The same procedure was
adopted for all substrates (1a-4b) (Supporting Information).
9,9-Bis(2-ethylhexyl)-9H-fluorene (1c): C H (0.43 g, 88%);
2
9
42
1
H NMR (400 MHz, CDCl ) 7.68 (d, 2H), 7.30 (m, 6H), 1.97 (m,
3
1
3
3
4H), 0.75 (m, 26H), 0.50 (m, 4H); C NMR (100 MHz, CDCl )
1
3
3
50.5, 141.5, 126.8, 126.5, 124.2, 119.7, 55.0, 44.7, 34.7, 34.7,
3.8, 28.2, 27.0, 22.8, 14.2, 10.4; exact mass 390.3287; HR MS
90.3253.
Experimental Section
Acknowledgment. We thank DST, India, and CSIR, In-
dia, for financial assistance. G.S. thanks CSIR for a Senior
Research Fellowship.
Materials. Alkyl halides, fluorene, and tetrabutylammonium
halides were used as received. Freshly distilled solvent was
always used for workup and purification processes. Milli-Q
grade water was used in all the experiments.
General Procedure Followed for the Dialkylation of Fluorene
1c). Fluorene (0.21 g, 1.26 mmol), 50% aq NaOH, and a
catalytic amount of tetrabutylammonium iodide (0.046 g, 10
mol %) were added to a flask. The flask was degassed three times
Supporting Information Available: Experimental details and
copies of spectral data for the compounds mentioned in the
tables. This material is available free of charge via the Internet at
http://pubs.acs.org.
(
J. Org. Chem. Vol. 75, No. 8, 2010 2717