914
Chemistry Letters Vol.38, No.9 (2009)
Reversible ArSE Aroylation of Naphthalene Derivatives
Akiko Okamoto and Noriyuki Yonezawaꢀ
Department of Organic and Polymer Materials Chemistry, Tokyo University of Agriculture and Technology,
2-24-16 Naka-machi, Koganei, Tokyo 184-8588
(Received July 2, 2009; CL-090624; E-mail: yonezawa@cc.tuat.ac.jp)
Reversible ArSE aroylation has been observed in the reac-
Table 1. ArSE aroylation of 2,7-dimethoxynaphthalene (1) with
4-chlorobenzoic acid derivatives 2a
tion of 2,7-dimethoxynaphthalene (1) with 4-chlorobenzoic
acid/acid chloride 2 with the aid of discrete acidic mediators.
The reaction readily gives 1-aroylated-, 3-aroylated-, and 1,8-di-
aroylated products. The product distribution clearly shows de-
pendence on the kind and strength of the acidic mediators and
the time-course of the distribution manifests dearoylation of
the productive aroylnaphthalenes. These reaction behaviors in-
cluding acid-strength-dependent reversibility are well interpret-
ed from the viewpoint of highly congested noncoplanar geome-
try of the polyaromatic ketone products.
R8 R1
R8
H
ArCO
H
R3
H
H
ArCO
R1
ArCO
ArCO
H
ArCOX X = Cl (2a), OH (2b)
MeO
OMe
R3
MeO
OMe
Acidic mediator
3
4
5
Ar = p-Cl-C6H4
1
3−5
Yieldb/%
Acidic
Acyl- Temp Time
donor /ꢁC
Entry
mediator
/h
3
4
5
1c
2e
3c
4f
5f
6g
7h
AlCl3 (3 equiv)d
AlCl3 (3 equiv)d
AlCl3 (1 equiv)d
PPA
PPA
P2O5–MsOH
TfOH (3 equiv)d
2a
2a
2a
2b
2b
2b
2a
0
0
0
70
100
60
50
2
2
6
2
2
7
70 12
0
0
0
0
7
10
80
0
0
5
1
0
Electrophilic aromatic substitution (ArSE) is one of the most
effective protocols for C–C bond formation in addition to metal-
catalyzed coupling methods. The Friedel–Crafts C–C bond for-
mation1 is a representative ArSE reaction and still receives con-
tinued interests.2 This well-known reaction is divided into two
distinct types, i.e., alkylation and acylation. The latter is further
categorized as alkanoylation giving alkyl aryl ketones and aroy-
lation affording diaryl ketones. Reactivity and successibility in
Friedel–Crafts reactions are recognized to depend substantially
on the electronic stability of the cationic intermediate and elec-
tron density of the aromatic substrates. The rather stable acylium
ions slowly undergo acylation and the resulting ketones are al-
most inert to prolonged acylation due to the strong electron-
withdrawing effect of the ketonic carbonyl group introduced.
This behavior is distinct from alkylation. On the other hand,
there is another dichotomy of regio-descrimination in ArSE reac-
tions as observed for the ꢀ- and ꢁ-substitution of naphthalene
derivatives, which is concerned with a reversible substitution
process to some extent. Gore and his co-workers have proposed
that the Friedel–Crafts ꢀ-alkylation of naphthalene is essentially
reversible.3 Contrarily, reversible alkanoylation has been little
observed except for acetyl group transfer4,5 and the reversible ar-
oylation has been seldom reported.5,6 The virtual irreversibility
of aroylation is probably due to the large resonance stabilization
by conjugation of the aryl–aryl ketone linkage.7–9
2
24
0
0
75 23
58 39
aReaction conditions: 2,7-dimethoxynaphthalene (1, 0.2 mmol),
acyl-donor 2 (0.4 mmol), N2 atmosphere. bIsolated yield. cIn
d
e
CH2CH2Cl2 (2.0 mL). Against 0.4 mmol of acyl-donor 2. In
nitrobenzene (2.0 mL). fPPA (6.4 g). gP2O5–MsOH (0.8 mL).
hIn CH2CH2Cl2 (0.5 mL).
lyst, a direct condensation reagent, and a Brønsted superacid.
When 1 was allowed to react with 2a in the presence of AlCl3,
3 was formed with high selectivity (Entries 1–3). Polyphospho-
ric acid (PPA)-mediated reaction of 1 with 2b gave a mixture of
4 and 5 or solely 5 in low conversions, respectively (Entries 4
and 5). On the other hand, both phosphorus(V) oxide–methane-
sulfonic acid mixture (P2O5–MsOH)12 and trifluoromethanesul-
fonic acid (TfOH) achieved sufficient conversion of 1 into the
aroylated products 4 and 5 with appreciably different product
distributions (Entry 6 vs. 7).
The time-course of the product distributions in the aroylation
reaction with different Brønsted acid strengths also shows a char-
acteristic feature of this transformation (Figure 1).11 With 5%
TfOH–95% TFA, the fraction of 3 maintains high conversion
throughout the reaction and further aroylation scarcely proceeds
(Figure 1a). With 50% TfOH–50% TFA, 4 increases rapidly at
the early stage followed by abrupt decrease and 5 increases with
time, whereas 3 is produced only in the early period and decreases
simply afterward (Figure 1b). In the presence of TfOH, 4 and 5
increase gradually in a constant ratio with steady decrease of 3
that is formed rapidly at the quite early stage (Figure 1c).
These results clearly manifest the reversibility of this ArSE ar-
oylation, i.e., progress of dearoylation of 3 and 4 (Scheme 1). The
increase of acid strength essentially accelerates dearoylation of 3
and 4, whereas that of 4 is depressed under superacidic conditions.
The ready formation of the congested polyaromatic mole-
cule of 4 and the dynamic interconvertibility of ArSE aroylation
of these molecules are well interpreted from electronic and steric
factors. In the X-ray crystal structures of 313 and 4,14 the aroyl
groups are twisted almost perpendicularly but a little tiltedly to-
In the course of the authors’ investigation to achieve consec-
utive and regioselective dual ArSE aroylation utilizing the elec-
tronic and steric characteristics of polyaromatic molecules,10
a
unique feature of ArSE aroylation of a naphthalene core is dis-
closed.
In this letter, the authors wish to introduce hitherto-unknown
reversible aroylation behavior in the acid-mediated reaction of
2,7-dimethoxynaphthalene (1) and 4-chlorobenzoic acid/acid
chloride 2 and discuss the reaction governing factors from the as-
pect of noncoplanar and highly congested structure of the pro-
duced molecules.
Table 111 shows the results of the reaction of 1 and 2 with
several acidic mediators such as a typical Friedel–Crafts cata-
Copyright Ó 2009 The Chemical Society of Japan
Okamoto, Akiko
