BF3-H2O catalyzed hydroxyalkylation of aromatics with aromatic aldehydes and dicarboxaldehydes: Efficient synthesis of triarylmethanes, diarylmethylbenzaldehydes, and anthracene derivatives

Article abstract of DOI:10.1021/jo901668j

(Figure Presented) BF₃-monohydrate is found to be an efficient and strong acid catalyst as well as an effective protosolvating medium suitable for the hydroxyalkylation of arenes with aromatic aldehydes. This reaction has been extended to aromatic dialdehydes, such as terephthalic dicarboxaldehyde and isoterephthalic dicarboxaldehyde, for the efficient synthesis of diarylmethylbenzaldehydes, which are useful synthons for various organic transformations. Further, successful one step convergent synthesis of various synthetically useful anthracene derivatives from phthalaldehyde was also achieved. BF₃-H₂O is less expensive and acts as an efficient substitute for nonoxidizing strong protic acids/superacids.

Full text of DOI:10.1021/jo901668j

pubs.acs.org/joc
BF3-H2O Catalyzed Hydroxyalkylation of Aromatics with Aromatic
Aldehydes and Dicarboxaldehydes: Efficient Synthesis of
Triarylmethanes, Diarylmethylbenzaldehydes, and
Anthracene Derivatives
G. K. Surya Prakash,* Chiradeep Panja, Anton Shakhmin, Eric Shah, Thomas Mathew,*
and George A. Olah*
Donald P. and Katherine B. Loker Hydrocarbon Research Institute and Department of Chemistry,
University of Southern California, 837 Bloom Walk, Los Angeles, California 90089-1661
gprakash@usc.edu
Received August 13, 2009
BF3-monohydrate is found to be an efficient and strong acid catalyst as well as an effective
protosolvating medium suitable for the hydroxyalkylation of arenes with aromatic aldehydes. This
reaction has been extended to aromatic dialdehydes, such as terephthalic dicarboxaldehyde and
isoterephthalic dicarboxaldehyde, for the efficient synthesis of diarylmethylbenzaldehydes, which are
useful synthons for various organic transformations. Further, successful one step convergent
synthesis of various synthetically useful anthracene derivatives from phthalaldehyde was also
achieved. BF3-H2O is less expensive and acts as an efficient substitute for nonoxidizing strong
protic acids/superacids.
Introduction
generate good Lewis acidic systems, and several reactions
have been studied.2 Because boron in BF3 is highly oxophilic,
complexation with protic oxygenated compounds such as
alcohols can give rise to strong Bronsted acid systems.3
Unlike other boron halides, hydrolysis of BF3 is very slow.
Meerwein in 1933 found that water can form stable com-
plexes with BF3 and the systems can act as Bronsted acids.4
Boron trifluoride1,2 is a well-known gaseous Lewis acid
(mp -127 °C and bp -100 °C/35 mmHg). BF3 alone or in
complex form with other n-donor molecules, such as diethyl
ether, dimethyl sulfide, acetic anhydride, and so on, can
(1) (a) Martin, D. R. In Kirk-Othmer Encyclopedia of Chemical Technology,
3rd ed.; Grayson, M., Ed.; Wiley: New York, 1980; Vol. 10, pp 685-693.
(b) Greenwood, N. N.; Thomas, B. S. In Comprehensive Inorganic Chemistry;
Trotman-Dickenson, A. F., Ed.; Pergamon: New York, 1973; Vol. 1, pp 956-973.
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therein.
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2018. (b) Hennion, G. F.; Hinton, H. D.; Nieuwland, J. A. J. Am. Chem. Soc.
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Chem. Soc. 1934, 56, 2689–2690.
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DOI: 10.1021/jo901668j
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Published on Web 10/28/2009
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2009 American Chemical Society

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Two types of water complexes are known with BF3: the
monohydrate (BF3-H2O) and the dihydrate (BF3-2H2O)
complexes. The dihydrate complex is very stable, less fuming
than the monohydrate and its acidity is close to that of 100%
nitric acid. On the other hand, BF3-H2O 1:1 complex is a
strong acidic system with the acidity close to that of 100%
sulfuric acid (Ho ∼ 12).5 These complexes can be prepared by
passing BF3 slowly into adequate amount of water with
proper cooling. BF3 monohydrate complex (colorless fum-
ing liquid, density of 1.8 g/mL, and mp 6.2 °C) is less
expensive than trifluoromethanesulfonic acid and non-
oxidizing in nature like trifluoromethanesulfonic acid. These
properties permit many acid-induced synthetic transforma-
tions, which were previously carried out using expensive
superacids. Over the years, we found that it can act as an
excellent acid system for a wide range of reactions, such as
preparation of alkyl nitrates and sulfides from carbonyl
compounds, thioacetalization of ketones, nitration of aro-
matics using potassium nitrate, halogenations of deactivated
aromatics using N-halosuccinimides, the Fries rearrange-
ment, and so on (Scheme 1), under mild reaction conditions.6
ylation, has been studied extensively.7,8 In most of the cases,
this reactionrequiredexpensive superacids,9 suchastrifluoro-
methanesulfonic acid, Magic acid, and so on. During our
ongoing efforts to introduce acid systems to replace expen-
sive acids, we decided to study the condensation reaction of
aromatic aldehydes (2 and 3) with various arenes using
BF3-H2O as the catalyst. We extended this methodology
to three isomeric dicarboxaldehydes-terephthalic dicarboxal-
dehyde (benzene-1,4-dicarboxaldehyde 3a), isoterephthalic
dicarboxaldehyde (benzene-1,3-dicarboxaldehyde 3b), and
phthalic dicarboxaldehyde (benzene-1,2-dicarboxaldehyde
3c) under similar conditions. Reactions of 3a and 3b with
arenes gave the corresponding diarylmethylbenzaldehydes
in high yields. However, the products from phthalaldehyde
(benzene-1,2-dicarboxaldehyde 3c) are identified as anthra-
cene derivatives. Many of these compounds are new, and the
reaction of only electron-rich aromatics with dialdehydes
under Lewis acid conditions have been known.10 Diaryl-
methylbenzaldehyde derivatives could be useful synthons for
many biologically and chemically important compounds.
For example, the hydrazone derivatives (e.g., compound
4a) of the diarylmethylbenzaldehydes are widely used as
charge-transporting material for electrographic photorecep-
tors showing improved charge transport, increase in sensi-
tivity, better residual potential characteristics, and better
durability.11 Compound 4b is known to be the agonists of
melanocortin receptors and shows high biological activities
for the treatment, control, or prevention of diseases and
disorders responsive to the activation of the melanocortin
receptors12 (Scheme 2).
SCHEME 1. BF3-H2O as an Acid Catalyst in Various Organic
Reactions
SCHEME 2. Synthetic Applications of Diarylmethyl Benzal-
dehyde Derivatives
Since 1886, acid-catalyzed condensation reaction of aro-
matic aldehydes with aromatics, also known as hydroxyalk-
Anthracene and its derivatives are important chemical
compounds, which possess diverse chemical and physical
properties. They are used to make major components
of electroluminescent devices and photothermographic
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1992, 465–466. (c) Olah, G. A.; Wang, Q.; Li, X.-Y.; Prakash, G. K. S. Synlett
1993, 32–34. (d) Olah, G. A.; Wang, Q.; Li, X.-Y.; Prakash, G. K. S. Synthesis
1993, 207–208. (e) Prakash, G. K. S.; Mathew, T.; Hoole, D.; Esteves, P. M.;
Wang, Q.; Rasul, G.; Olah, G. A. J. Am. Chem. Soc. 2004, 126, 15770–15776.
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8660 J. Org. Chem. Vol. 74, No. 22, 2009

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materials,13 combination marker for liquids,14 liquid crys-
tals,15 organic thin film transistors,16 and several other
commercially important substances.
Herein, we report the results of our study on the con-
densation reaction of aromatic aldehydes and dialdehydes
with aromatics under superelectrophilic activation using
BF3-H2O as the catalyst as well as the reaction medium.
strated the mechanistic aspects of triflic acid-catalyzed reac-
tions of cinnamaldehyde and nitroolefins with benzene, in
which many multiply charged cationic species (dicationic
and tricationic) were involved.22 Later, Olah and co-workers
have carried out computational studies (ab initio calcula-
tions) on similar systems to find out the possible formation
of dicationic intermediates and their properties in super-
acids. Their studies indicated that the most preferred di-
cationic intermediate is the O,C-(aromatic) dication (5a,b)
and not the O,O-diprotonated system (5c).7a,b However,
recent studies on zeolite-catalyzed hydroxyalkylation by
Sommer et al. suggested that the intermediacy of mono-
cationic species is also important in these reactions.7e
Results and Discussion
Condensation of Aromatic Aldehydes with Aromatics. It
has been shown that acid-catalyzed condensation reaction of
aromatic aldehydes with aromatics initially produces diaryl-
methanols, which undergo further reaction with another
molecule of the arene to provide the corresponding triaryl-
methane derivatives. The acidity dependence of this reac-
tion has been studied and reported earlier.9 In the presence of
very strong Lewis acids such as AlCl3, benzene and benzal-
dehyde give a mixture of products.17 The effect of basicity of
carbonyl compounds on this reaction has also been studied
by Hatzsch,18 using 100% H2SO4. However, this reaction
does not occur to any significant degree with 100% H2SO4 at
room temperature. This relates to the fact that formation of a
highly electron-deficient species under strong protosolvoly-
tic conditions is required as a driving force for this reaction.
Carboxonium ions were first studied by Meerwein.19 Studies
on stability and reactivity of carbocations have shown the
effect of neighboring group participation and its conse-
quences on attenuating the electrophilicity of the carboca-
tions.20 In acid medium, if protonation occurs on the oxygen
atom, the resulting cation is stabilized both by the oxygen
and the neighboring phenyl group, thus making it a relatively
weak electrophile. To decrease this neighboring group parti-
cipation effect and increase the electrophilicity of the carbo-
nyl carbon, further protonation of the system is required.
According to Olah’s definition of superelectrophiles, under
superacidic conditions, further protonation or protosolva-
tion of the protonated aldehydes is possible,21 which leads to
very reactive intermediates (superelectrophiles). This super-
electrophilic or multi-ionic intermediate can undergo succes-
sive condensation reactions with weaker nucleophiles like
aromatics (Scheme 3).21b-f Ohwada and Shudo have demon-
SCHEME 3. Mechanism for the Superacid-Catalyzed Conden-
sation Reaction of Benzaldehyde with Benzene
During our previous studies using BF3-H2O, we found
that BF3-H2O can act both as a strong acid catalyst and an
efficient protic solvent/protosolvating medium.6e-g It offers
optimum acidity for the halogenation of many deactivated
aromatics, which are not feasible under normal acidic con-
ditions. Intrigued by these results, we have conducted the
reactions of different aldehydes with various aromatics using
BF3-H2O under varying reaction conditions (Scheme 4). As
expected, BF3-H2O acts as a strong acid catalyst as well as a
good reaction medium for effective protosolvation of pro-
tonated aldehydes. Depending on the nature of aldehydes
and the aromatics, the reaction occurs smoothly at room
temperature and above, giving the triarylmethane products
in good to excellent yields in most cases. It is important to
note that these reactions are relatively clean making work up
and purifications rather easy. Results are summarized in
Tables 1 and 2. However, during the reaction of electron rich
aldehydes with aromatics, we observed transformylation
reaction followed by arylation. This type of phenomenon
has already been reported in the literature.23 Thus, when
(13) Kong, S. H.; Skoug, P. G.; Sakizadeh, K. Eur. Pat. 1180722, 2002.
(14) Spall, D.; Aleen, T. M.; Goeller, R.; Kottenstette, P. U.S. Pat. 19939,
2005.
(15) Takashi, K.; Junji, M. Jpn. Pat. 212799, 2003.
(16) Smith, T.; Pellerite, M. J.; Kelley, T. W.; Muyres, D. V.; Vogel, D. E.;
Vogel, K. M.; Boardman, L. D.; Dunbar, T. M. U.S. Pat. 175551, 2003.
(17) (a) Schaarschmidt, A.; Hermann, L.; Szemzo, B. Ber. Dtsch. Chem.
Ges. 1925, 58, 1914–1916. (b) Hofmann, J. E.; Schriesheim, A. In Friedel-Crafts
and Related Reactions; Olah, G. A., Ed.; Wiley: New York, 1964; Vol. II, Chapter
XIX, pp 616-621.
(18) Hantzsch, A. Z. Phys. Chem. (Leipzig) 1909, 65, 41–60.
(19) (a) Meerwein, H.; Hederich, V.; Morschel, H.; Wunderlich, K. Ann.
1960, 635, 1–21. (b) Meerwein, H.; Allendorfer, H.; Beckmann, P.; Kunert,
F.; Morschel, H.; Pawellek, F.; Wunderlich, K. Angew. Chem. 1958, 70, 211–
15. (c) Meerwein, H.; Borner, P.; Fuchs, O.; Sasse, H. J.; Schrodt, H.; Spille,
J. Chem. Ber. 1956, 89, 60–79.
(20) (a) Pauling, L. J. Chem. Phys. 1933, 1, 56–59. (b) Babb, J. F.; Du, M.
L. Chem. Phys. Lett. 1990, 167, 273–277.
(21) (a) Olah, G. A.; Germain, A.; Lin, H. C.; Forsyth, D. A. J. Am.
Chem. Soc. 1975, 97, 2928–2929. (b) Olah, G. A. Angew. Chem., Int. Ed. Engl.
1993, 32, 767–788. (c) Olah, G. A.; Prakash, G. K. S.; Lammerstma, K. Res.
Chem. Intermed. 1989, 123, 141–159. (d) Olah, G. A.; Mathew, T.; Esteves,
P. M.; Etzkorn, M.; Rasul, G.; Prakash, G. K. S. J. Am. Chem. Soc. 2001,
123, 11556–11561. (e) Olah, G. A.; Klumpp, D. A. Acc. Chem. Res. 2004, 37,
211–220. (f) Olah, G. A.; Klumpp, D. A. Superelectrophiles and their Chemistry;
Wiley-Interscience: Hoboken, NJ, 2008.
(22) (a) Ohwada, T.; Yamagata, N.; Shudo, K. J. Am. Chem. Soc. 1991,
113, 1364–1373. (b) Okabe, K.; Ohwada, T.; Toshiharu, O.; Shudo, K.
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benzene was reacted with p-tolualdehyde, mostly triphenyl-
methane was formed; p-anisaldehyde gave a mixture of
triphenylmethane and phenol; 2-naphthaldehyde gave naph-
thalene, 2-naphthol, and triphenylmethane.
rich aromatics smoothly react withbenzaldehyde compared to
the electrondeficient aromatics. Reactions ofbenzaldehyde2a
with aromatics carrying electron withdrawing groups, such
as halobenzenes, were sluggish. However, when benzaldehyde
was replaced by an electron deficient aldehyde, such as
nitrobenzaldehyde 2g, the reaction with halobenzenes became
faster and went to completion (Table 2, entries 5, 6, and 7).
This clearly shows how the substrates and reaction profile can
be tuned in favor of product formation at a faster rate. In the
case of substituted aromatics, para,para-derivatives were
found to be the major component in the product mixture.
Highly deactivated aromatics such as nitrobenzene and
dihalobenzenes do not react even with activated aldehydes
under similar reaction conditions.
Even though the product is a mixture of various isomers
(para,para-isomer as the major), chemical yields were found to
be high. The condensation of aldehydes with aromatics can be
carried out using BF3-monohydrate in a dual role, as a suitable
protic solvent and as an efficient catalyst, under moderate reac-
tion conditions. Reaction works well with varieties of aldehydes
and arenes. As mentioned earlier, reactions of aldehydes with
electron rich aromatics are more facile compared to electron
poor systems. Reactions are often very simple, clean and do not
require further purification in most cases. Because the reaction
worked well with aromatic monoaldehydes, studies were
extended to three isomeric aromatic dialdehydes.
SCHEME 4. Reaction of Aromatic Aldehydes with Aromatics
under BF3-H2O Catalyzed Conditions
TABLE 1. Reaction of Aldehydes with Benzene under Superelectro-
philic Activation
Condensation of Terephthalic Dicarboxaldehyde (3a) with
Aromatics. Because the reaction of dicarboxaldehydes with
arenes has not been explored to any significant degree, we
decided to carry out a detailed study on the reactions of
aromatic dicarboxaldehydes with arenes. Only a few refs10,24
are available regarding the reaction of aromatic dicarboxal-
dehydes with aromatics. As early as 1886, Oppenheimer20
mentioned that 100% H2SO4 can catalyze the reaction of
benzene and terephthalic dicarboxaldehyde to give rise to the
corresponding diarylmethyl benzaldehyde 8. Interestingly,
only one of the two aldehyde functional groups reacts under
the reaction conditions. However, a detailed description of
the reaction conditions was not available. When we per-
formed the reaction using terephthalic dicarboxaldehyde
and different aromatics with BF3-H2O as catalyst, we
obtained the corresponding 4-diarylmethyl benzaldehyde
derivatives (8) in high yields and purity (Scheme 5, Table 3).
Further hydroxyalkylation using the second aldehyde func-
tional group to obtain the tetraaryl derivative was not
observed in these cases. Even after the products, diaryl-
methylbenzaldehyde derivatives (8), were separated and
treated with aromatics in excess BF3-H2O, no products
due to second hydroxyalkylation step could be detected.
Presence of two arene moieties in the neighborhood could
reduce the electrophilicity of the protonated carbonyl center
to such an extent that further attack by a weak nucleophile
(arene in this case) would not occur. Also, the effect of
protosolvation occurring in the ring bearing the carbonyl
function could be reduced significantly, which in turn would
reduce the electrophilicity of the protonated carbonyl func-
tional group restricting further attack by weak nucleophiles.
Electron-rich aromatics undergo reactions under ambient
conditions (Table 3, entries 2, 3, 4, and 8), whereas electron
poor aromatics need higher temperature for the completion of
To explore the efficacy of BF3-H2O catalyzed hydroxyalk-
ylation reaction, we have studied the reactions of different
aromatics with benzaldehyde initially. We found that electron
(24) Oppenheimer, H. Chem. Ber. 1886, 19, 2028–2030.
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TABLE 2. Reaction of Aromatic Aldehydes with Different Aromatics under BF3-H2O Catalyzed Conditions
SCHEME 5. Reaction of Terephthalic Dicarboxaldehyde with
Aromatics under BF3-H2O Catalyzed Conditions
isomers. When the reaction was monitored carefully using
GCMS at various time intervals, the progress of the reaction
was found to be sequential. It was found that the initial attack
of the arene to the dialdehyde was very fast, but further attack
by a second molecule of arene leading to the final product was
much slower. However, the reactions are very clean, giving the
products in good to excellent yields in most cases.
Condensation of Isoterephthalic Dicarboxaldehyde (3b)
with Aromatics. Similar to terephthalic dicarboxaldehyde
(3a), isoterephthalic dicarboxaldehyde (3b) also gave the
corresponding 3-diarylmethylbenzaldehyde derivatives (9)
when treated with aromatics in BF3-H2O (Scheme 6). The
reaction with electron-rich aromatics can be performed under
ambient temperature, whereas aromatics with an electron
withdrawing group require higher temperatures. However,
the reaction (Table 3, entries 1, 5, 6, and 7). However, electron
deficient aromatics such as dihalobenzenes and nitrobenzene
do not react under the reaction conditions. In the case of
substituted aromatics, para,para-derivatives were obtained as
the major product, along with small amountsof other possible
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TABLE 3. Reaction of Terephthalic Dicarboxaldehyde (3a) with Aromatics
*Reaction time for 1a is 8 h, and for all other substrates, 16 h.
SCHEME 6. Reaction of Isoterepthalic Dicarboxaldehyde (3b)
with Aromatics under BF3-H2O Catalyzed Conditions
similar to the case of terephthalic dicarboxaldehyde, nitro and
dihalogenated aromatics do not undergo the condensation
reaction with isoterephthalic dicarboxaldehyde. With unsym-
metrical systems mostly para,para derivatives were obtained
with small amounts of other possible isomers. The results are
shown in Table 4. The mechanism must be similar to that
involved in terepthalic dicarboxaldehyde reaction.
Condensation of Phthalic Dicarboxaldehyde (3c) with Aro-
matics. Reaction of phthalic dicarboxaldehyde (3c) with
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TABLE 4. Reaction of Isoterephthalic Dicarboxaldehyde (3b) with Aromatics under BF3-H2O Catalyzed Conditions
aromatics interestingly gave anthracene derivatives as major
products. Direct synthesis of anthracene derivatives is rare.
Most of the methods available to synthesize anthracene
derivatives are associated with mainly Suzuki coupling25 or
functional transformation of the anthracene moiety. Hence,
this methodology could be useful for the synthesis of anthra-
cene derivatives26 12-14 directly from the aromatics and
phthalic dicarboxaldehyde (3c). We attempted the conden-
sation with a variety of aromatics and found that the reaction
works well only with electron-rich systems. With electron-
deficient systems the reactions were very sluggish. The results
are shown in Scheme 7. In most cases, we obtained the
9-arylanthracenes 13 as the major product. However, with
(26) (a) Kamata, K.; Kasai, J.; Yamaguchi, K.; Mizuno, N. Org. Lett. 2004,
6, 3577–3590. (b) Nakamichi, N.; Kawabata, H.; Hayashi, M. J. Org. Chem.
2003, 68, 8272–8273. (c) Dektar, J. L.; Hacker, N. P. J. Org. Chem. 1990, 55,
639–647. (d) Brice, L. K.; Katstra, R. D. J. Am. Chem. Soc. 1960, 82, 2669–2670.
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SCHEME 7. Reaction of Phthalic Dicarboxaldehyde with Aromatics under Superelectrophilic Conditions
SCHEME 8. Mechanism for the Condensation Reaction of Dicarboxaldehyde with Aromatics in BF3-H2O
tetramethylbenzene (1j), 1,2,3,4-tetramethylanthracene (12j)
was found to be the major product. With toluene, as
expected, a mixture of anthracene derivatives was formed,
in which 9-tolyl-2-methylanthrace (13b) was present in sig-
nificant amount along with appreciable amount of 9,10-
ditolyl-2-methylanthracene (14b). Similar results were also
obtained with p-xylene (1c) and m-xylene (1d). One of the
major difficulties associated with this methodology is in the
separation of the products due to their very close Rf values in
the TLC. In some cases, though the isomers were insepar-
able, their formation has been confirmed by GCMS and
NMR analysis. Despite the problem associated with the
product isolation and purification, this methodology can
still offer an efficient route toward the one pot synthesis of
anthracene derivatives.
Formation of Diarylmethylbenzaldehydes. It is clear that
the reaction must proceed through a diprotonated dicationic
intermediate in which one of the protonated aldehyde groups
is enhancing the electrophilicity of the other protonated
aldehyde group through a synergic effect. Thus, as shown
in Scheme 8, the reaction is clearly found to be a hydroxy-
alkylation to produce a secondary carbinol which undergoes
further protonation followed by elimination of water to form
a diphenylmethyl dication. This dicationic intermediate
acts as an efficient electrophile for further reaction with
aromatics to form the triarylmethane derivatives.
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SCHEME 9. Reaction of Phthalic Dicarboxaldehyde (3c) with Aromatics under Superelectrophilic Activation
Formation of Anthracenes. The main driving force for this
reaction is the superelectrophilic activation of phthalal-
dehyde by BF3-H2O followed by its Friedel-Crafts hydro-
xyalkylation on the arene through the highly electrophilic
protosolvated carbonyl center. In the case of isophthalal-
dehyde and terephthaldehyde it is found that initial hydro-
xyalkylation produces the corresponding diphenylme-
thanol and subsequently diphenylmethyl dication, which
acts as an efficient electrophile for further Friedel-Crafts
alkylation with aromatics to form the triarylmethane
derivatives. The second aldehyde group is unaffected.
However, in the case of phthaladehyde, the extreme proxi-
mity of one of the aryl ring to the second protonated
aldehyde group leads to intramolecular cyclization
(cycliarylation) giving rise to different anthracene deriva-
tives (Scheme 9). If the cyclization took place after initial
hydroxyalkylation step, it would follow the pathway (ii)
leading to a 9,10-diol (15), which on aromatization
(by dehydration) followed by tautomerism yields the
corresponding anthrone (16) under the reaction conditions.
However, formation of anthrone (16) was not found in any
of these cases. This observation suggests that successive
hydroxyalkylation with the arenes occurs on only one of the
aldehyde groups and the greater proximity of the aryl
rings with the second aldehyde group (which remains
protosolvated) in the product (triarylmethane derivative)
promotes intramolecular cyclization to yield anthracenes
(12), 9-arylanthracenes (13), and 9,10-diarylanthracenes
(14) through subsequent steps (pathway i). In the case
of 1,2,3,4-tetramethylanthracene, due to the enhanced
nucleophilicity, the strong steric effect, and the proximity,
sequential hydroxyalkylation is immediately followed by
cyclization and aromatization via elimination of 1,2,3,4-
tetramethylphenyl cation. While BF3-H2O acts as a strong
Bronsted acid medium, it is an effective aqueous me-
dium also. In aqueous media, formation and stabiliza-
tion of phenyl cations by hydration (highly exothermic by
51.2 kcal/mol) is known and detailed studies have been
J. Org. Chem. Vol. 74, No. 22, 2009 8667

Prakash et al.
JOCArticle
carried out in this area.27,28 Basically the three competing
pathways, (a) formation of 9-arylanthracenes 13 from 10,
(b) further Friedel-Crafts alkylation by the highly reactive
diphenylmethyl cation 11 on another arene molecule and
subsequent formation of 9,10-diarylanthracenes 14 by oxi-
dation, and (c) the formation of anthracene 12 from 10
through 11, contribute to the formation of all major pro-
ducts 12, 13, and 14. Formation of the 9,10-diarylanthra-
cenes (14) from the 9,10-dihydro derivatives could involve
an oxidative dehydrogenation step in which the formation
of a radical cation species29 is suggested as an intermediate.
This kind of phenomenon is common for the condensation
of polynuclear aromatics under acidic conditions. One
example that involves such a step is the Scholl’s reaction.30
Because 9-arylanthracenes (13) did not provide any 9,10-
diarylanthracenes and anthracene under the reaction con-
ditions (both in the presence and absence of aromatics),
formation of anthracenes (12) and 9,10-diarylanthracenes
(14) by transarylation of 9-arylanthracenes (13) is clearly
ruled out.
organic synthesis. We expect wide use of less expen-
sive BF3-H2O as an efficient substitute for nonoxidizing
strong protic acids in a variety of acid-catalyzed organic
reactions.
Experimental Section
General Procedure for the Condensation Reaction of Alde-
hydes/Dicarboxaldehydes with Aromatics using BF3-H2O as the
Acid Catalyst. Aldehyde or dicarboxaldehyde (1 mmol) and neat
arene (2 mL; for solid aromatics, 4 equiv) were taken in a
pressure tube (30 mL). To this mixture, BF3-H2O (50 equiv,
4.2 g; prepared by reported procedure6e) was added and sealed.
The mixture was stirred and heated at the required temperature
under closed condition until the completion of the reaction.
Progress of the reaction was monitored by TLC and GCMS.
After the reaction, the reaction mixture was then poured into
ice-water (10 mL) and extracted with CH2Cl2 (3 ꢀ 20 mL).
Combined organic layer was washed with aq NaHCO3 solution,
then with brine solution, dried over anhydrous Na2SO4, and
then solvent was removed under reduced pressure to obtain the
crude product. The crude product was further purified by
column chromatography over silica gel (65-250 mesh) using
hexane-ethyl acetate 2-10% as eluent. Products were charac-
terized by analyzing their spectral data (1H, 13C, 19F NMR,
GCMS, and HRMS data).
9-(2,5-Dimethylphenyl)-1,4-dimethylanthracene (13c). Pre-
pared by general procedure, yield 75%. 1H NMR δ 1.80
(s, 3H), 2.35 (s, 3H), 2.37 (s, 3H), 2.81 (s, 3H), 7.04 (s, 1H),
7.14 (s, 2H), 7.23 (dd, J = 7.78 Hz, J = 1.55 Hz, 1H), 7.27-7.32
(m, 2H), 7.38-7.42 (m, 1H), 7.44 (d, J = 8.79 Hz, 1H), 8.04 (d,
J = 8.79 Hz, 1H), 8.54 (s, 1H); 13C NMR δ 19.3, 19.9, 21.0, 22.2,
122.5, 123.1, 124.6, 125.3, 126.3, 128.3, 128.4, 128.8, 129.7,
129.8, 130.3, 130.7, 131.8, 134.1, 134.56, 134.63, 135.0, 135.9,
138.5; MS (EI) m/z 309.3 (M•þ); HRMS (EI) m/z calcd for
C24H22, 310.1722; found, 310.1719.
Conclusions
BF3-monohydrate is found to be an efficient and strong
Bronsted acid catalyst for the hydroxyalkylation of aro-
matics with aldehydes. These reactions show that BF3-H2O
can be used as a very effective protosolvating medium as well
as a catalyst without the use of any additional solvent during
the reaction. Diarylmethylbenzaldehydes, which can be use-
ful synthons for various organic transformations, can be
achieved easily from isoterephthalic dicarboxaldehyde and
terephthalic dicarboxaldehyde using this method. Synthesis
of various anthracene derivatives from phthalic dicarboxa-
ldehyde, further adds to the importance of this method in
Acknowledgment. This paper is respectfully dedicated
to Professor M. V. George, National Institute for Inter-
disciplinary Science and Technology (NIIST), Trivandrum,
India. Support of our work by Loker Hydrocarbon Research
Institute is gratefully acknowledged.
(27) Glaser, R.; Wu, Z. J. Am. Chem. Soc. 2004, 126, 10632–10639.
(28) (a) Baily, F.; Barthen, P.; Frohn, H.-J.; Kockerling, M. Z. Anorg.
Allg. Chem. 2000, 626, 2419–2427. (b) Winkler, M.; Sander, W. J. Org. Chem.
2006, 71, 6357–6367. (c) Winkler, M.; Sander, W. Angew. Chem., Int. Ed.
2000, 39, 2014–2016.
(29) (a) Friedel-Crafts and Related Reactions; Olah, G. A., Ed.; Wiley: New
York, 1964; Vol. II, p 979. (b) Tanaka, M.; Nakashima, H.; Fujiwara, M.; Ando, H.;
Souma, Y. J. Org. Chem. 1996, 61, 788–792. (c) Clowes, G. A. J. Chem. Soc. C
1968, 2519–2526.
Supporting Information Available: Experimental proce-
dure, spectral data, and copies of 1H, 13C, and 19F NMR spectra
of the products. This material is available free of charge via the
Internet at http://pubs.acs.org.
€
(30) (a) Scholl, R.; Seer, C.; Weitzenbock, R. Ber. Dtsch. Chem. Ges. 1910,
43, 2202–2209. (b) Scholl, R.; Seer, C. Annalen 1912, 394, 111. (c) Scholl, R.;
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8668 J. Org. Chem. Vol. 74, No. 22, 2009