Halophenol rearrangement in Lewis acid-catalyzed Friedel-Crafts conditions: Evidence of competitive initial protonation and acylation

Article abstract of DOI:10.1071/CH08084

Halogen rearrangement was observed during the Lewis acid-catalyzed Friedel-Crafts reaction of phthalic anhydride with bromophenols or bromoanisole. Further investigation revealed that 2-, 3-, and 4-bromophenols undergo rearrangement into other isomers under these reaction conditions. Product distribution from these reactions suggested that halogen rearrangement takes place during the s-complex intermediate of the condensation step. Furthermore, iodophenol undergoes hydrodeiodination rapidly rather than rearrangement, whereas chlorophenol does not undergo rearrangement at all. CSIRO 2008.

Full text of DOI:10.1071/CH08084

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2008, 61, 821–825
Halophenol Rearrangement in Lewis Acid-Catalyzed
Friedel–Crafts Conditions: Evidence of Competitive
Initial Protonation and Acylation
Koushik Saha,A Nordin H. Lajis,A,B,E Faridah Abas,A,C Nabil Ali Naji,A
A. Sazali Hamzah,D and Khozirah ShaariA,B
ALaboratory of Natural Products, Institute of Bioscience, University Putra Malaysia,
43400 Serdang, Selangor, Malaysia.
BDepartment of Chemistry, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
CDepartment of Food Science, Faculty of Food Science and Technology,
University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
DDepartment of Chemistry, Faculty of Applied Science, University of Technology Mara,
40450 Shah Alam, Selangor, Malaysia.
ECorresponding author. Email: nhlajis@ibs.upm.edu.my
Halogen rearrangement was observed during the Lewis acid-catalyzed Friedel–Crafts reaction of phthalic anhydride with
bromophenols or bromoanisole. Further investigation revealed that 2-, 3-, and 4-bromophenols undergo rearrangement
into other isomers under these reaction conditions. Product distribution from these reactions suggested that halogen
rearrangement takes place during the s-complex intermediate of the condensation step. Furthermore, iodophenol undergoes
hydrodeiodination rapidly rather than rearrangement, whereas chlorophenol does not undergo rearrangement at all.
Manuscript received: 27 February 2008.
Final version: 12 August 2008.
R1
R4
OR1
Introduction
O
O
O
R2
R3
R2
R3
(i)
There is continuing interest in the synthesis of anthraquinones
not only because of their biological activity but also because
of their potential as valuable precursors for the synthe-
sis of biologically active compounds such as rhein and
diacerhein,[1] anthracyclinone and anthracyclin,[2] as well as
topopyrone.[3] Some anthraquinones exhibit antimicrobial,[4]
antiplasmodial,[5] antitumour,[6,7] and antiviral[8] properties.
The most useful methods to prepare the anthraquinone back-
bone are through Friedel–Crafts condensations[9–11] as well as
those based on cycloaddition such as the Diels–Alder[12] reac-
tion and the use of phthalides.[13–15] As part of our strategy
in the simple and low-cost synthesis of anthraquinones, we
intended to prepare 4-bromo-1-hydroxyanthraquinone by treat-
ing 4-bromophenol with phthalic anhydride.[16] The product can
then be debromoalkylated to produce the desired anthraquinone.
To our surprise, we isolated various rearranged products on
several attempts of our synthesis.
ꢀ
O
O
R4
Halophenols or
methoxy-halobenzene
Hydroxy- or
halohydroxyanthraquinone
1
2 R1 ꢁ R2 ꢁ R3 ꢁ H, R4 ꢁ Br
3 R1 ꢁ CH3, R2 ꢁ R3 ꢁ H, R4 ꢁ Br
4 R1 ꢁ R2 ꢁ R4 ꢁ H, R3 ꢁ Br
5 R1 ꢁ R3 ꢁ R4 ꢁ H, R2 ꢁ Br
6 R1 ꢁ R2 ꢁ R3 ꢁ H, R4 ꢁ Cl
7 R1 ꢁ R2 ꢁ R3 ꢁ H, R4 ꢁ I
8
9
R1 ꢁ OH, R2 ꢁ R4 ꢁ H, R3 ꢁ Br
R1 ꢁ OH, R2 ꢁ R3 ꢁ H, R4 ꢁ Br
10 R1 ꢁ R4 ꢁ H, R2 ꢁ OH, R3 ꢁ Br
11 R1 ꢁ OH, R2 ꢁ R3 ꢁ R4 ꢁ H
12 R1 ꢁ R3 ꢁ R4 ꢁ H, R2 ꢁ OH
13 R1 ꢁ Br, R2 ꢁ R4 ꢁ H, R3 ꢁ OH
14 R1 ꢁ Br, R2 ꢁ OH, R3 ꢁ R4 ꢁ H
15 R1 ꢁ OH, R2 ꢁ R3 ꢁ H, R4 ꢁ Cl
Scheme 1. Reagents and conditions: (i) anhydrous AlCl3, NaCl,
165–170◦C, 45 min.
Phthalic anhydride 1 and halogenated benzene derivatives 2–
7 were used as the starting materials in the presence of anhydrous
aluminium chloride as Lewis acid. The mixture of starting mate-
rials was introduced into melted anhydrous aluminium chloride
and sodium chloride, and the reaction mixture was heated at
165–170◦C (external temperature) for 45 min. After allowing it
to cool, the reaction mixture was quenched by the addition of
ice and hydrochloric acid. The product mixture was extracted
into ethyl acetate and its components, 8–15, were purified using
column chromatography. The total yields of the reaction were
found to be moderate (35–50%, Scheme 1). The overall results
are presented in Table 1. This procedure was found to be the
best in terms of the total yields after several modifications
of the reaction conditions were conducted. The preparation of
anthraquinone from phthalic anhydride is a double condensa-
tion reaction in which the second condensation step is apparently
more sluggish, possibly owing to the less-efficient electrophilic
attack on a relatively electron-deficient system.
© CSIRO 2008
10.1071/CH08084
0004-9425/08/100821

822
K. Saha et al.
Table 1. Product ratios and percentage yield of reactions
Halophenols
% of product based on high pressure liquid chromatography
Total overall yield
based on starting
halophenols [%]
8
9
10
11
12
13
14
15
4-Bromophenol 2
4-Bromoanisole 3
3-Bromophenol 4
2-Bromophenol 5
4-Chlorophenol 6
4-Iodophenol 7
48
49
66
17
–
22
23
2
3
–
16
14
–
52
–
8
8
10
3
–
22
6
6
–
15
–
78
–
–
22
–
–
–
–
–
–
10
–
–
–
–
–
–
100
–
50
35
49
40
47
36
–
–
–
Table 2. Percentage yields of products obtained from heating starting halo-
phenols and haloanisole at 120–130◦C in melted NaCl and AlCl3 for 10 min
Halophenols
% of products (based on high pressure liquid chromatography)
4-Halophenol 3-Halophenol 2-Halophenol
Phenol
4-Bromophenol 2
4-Bromoanisole 3
3-Bromophenol 4
2-Bromophenol 5
4-Chlorophenol 6
4-Iodophenol 7
65
74
17
52
–
30
21
77
25
–
–
–
18
–
–
–
5
5
6
5
86
86
14
–
Results and Discussion
followed by rearrangement or hydrodebromination. It was also
suggested that 3-bromophenol is the most thermodynamically
stable of the isomeric products. To our knowledge, this halogen
rearrangement as well as hydrodehalogenation of bromo- and
iodophenols in the presence of a simple Lewis acid represent the
first report of such an observation. Recently, hydrodeiodination
and hydrodebromination using Hβ-zeolite as catalyst have also
been reported.[18]
Friedel–Crafts condensation of 4-bromophenol 2 with phthalic
anhydride 1 gave 3-bromo-1-hydroxyanthraquinone 8 as the
major component (48% of the total product) along with four
other by-products as shown in Table 1. Whereas 4-bromo-1-
hydroxyanthraquinone 9 was the expected product, 3-bromo-1-
hydroxyanthraquinone 8 and 3-bromo-2-hydroxyanthraquinone
10 were the unexpected rearranged products from this reaction,
while 1-hydroxyanthraquinone 11 and 2-hydroxyanthraquinone
12 were the debrominated ones. When 4-bromoanisole 3 was
used as the starting material, a slightly lower yield of the prod-
uct mixture (35% overall yield) containing the same components
with comparatively similar composition was obtained. All prod-
ucts were demethylated as anhydrous aluminium chloride or
bromide is also known as a demethylating agent.[16]
To further understand this phenomenon, 3-bromophenol
4 and 2-bromophenol 5 were used as starting materials. In
the case of 4, the products were composed of 3-bromo-1-
hydroxyanthraquinone 8 as the major product along with 4-
bromo-1-hydroxyanthraquinone 9, 1-hydroxyanthraquinone 11,
and 1-bromo-3-hydroxyanthraquinone 13. The rearrangement
product 9 seemed to represent a minor component in the product
mixture. When compound 5 was used as the starting material,
the three expected products, 3-bromo-2-hydroxyanthraquinone
10, 1-bromo-2-hydroxyanthraquinone 14, and 2-bromo-1-
hydroxyanthraquinone (<1%, not reported) were isolated.
Along with these are the rearrangement products 3-bromo-1-
hydroxyanthraquinone 8 and 4-bromo-1-hydroxyanthraquinone
9, as well as the debrominated products 1-hydroxyanthraquinone
11 and 2-hydroxyanthraquinone 12 with a total yield of 40%.
Rearrangement and hydrodebromination of bromophenols
in the presence of superacid (SbF5–HF) have been reported
and the reaction mechanism has also been discussed.[17] In the
report by Jacquesy and Jouannetaud, initial protonation of the
halogen-bearing carbon to produce the s-complex was invoked
When 4-bromophenol 2 was heated up to 165–170◦C in
NaCl, no rearrangement products were detected, thus indicat-
ing that aluminium chloride was required for the rearrange-
ment. Heating in aluminium chloride and sodium chloride
at these temperatures, however, destroyed this compound.
4-Bromo-1-hydroxyanthraquinone 9 was also heated, under
similar conditions as in the preparation of anthraquinone, but
no reaction or rearrangement product was detected, suggest-
ing that no rearrangement of bromohydroxyanthraquinones take
place after their formation in this temperature range. This is in
contrast to an earlier report on the rearrangement of 1-bromo-
2-hydroxyanthraquinone to 3-bromo-2-hydroxyanthraquinone
when it was heated at 310–320◦C.[19]
In order to establish the possible course of this rearrange-
ment, we introduced the starting bromo-and iodophenols (2, 4,
5, and 7) as well as 4-bromoanisole 3 separately into the melt
of aluminium chloride and sodium chloride (external temper-
ature 120–130◦C). The reaction mixture was allowed to stand
for 10 min at this temperature and decomposed with ice and
hydrochloric acid and then worked up in the normal way. The
percentages of the corresponding products were determined
based on the integration of the respective proton signals as well
as by high pressure liquid chromatography (HPLC). The results
of these experiments, as presented in Table 2, clearly indicated
that bromophenols underwent rearrangement as well as hydro-
debromination into phenol. Rearrangement may also take place
in the case of 4-iodophenol but hydrodeiodination seemed to be

Halophenol Rearrangement
823
p-Bromophenol
more prominent than in the case of bromophenols such that no
rearranged products were observed. From these experiments, it
seems that rearrangement may have occurred in the presence of
aluminium chloride.
OH
OH
OH
OH
OH
(III)
R
R
R
ꢂBrꢀ
R
ꢀ
The major products 8 and 9 from Friedel–Crafts condensa-
tion of 4-bromophenol 2 and 4-bromoanisole 3 are rationalized
to be derived from initial acylation at the C2 (ortho to hydroxyl,
intermediateI)followedbyrearrangementintointermediate(VI)
and a second intramolecular condensation (Scheme 2).Although
initial rearrangement of 2 or 3 to 3-bromophenol followed by
acylation and intramolecular condensation may also lead to 8,
the absence of the possible alternative product 13 suggests that
this mechanistic route is not preferred. The second major prod-
uct 9 may also be derived from either intermediate (I) or (IV)
through initial acylation at the C3. The lower yield of product
9 indicates that acylation at C2 is more prominent than at C3,
which could be associated with the steric effect of the bromo
at C4 or electronic effect of the OH groups. The formation of
product 10 in a relatively substantial ratio, however, may not
be explained by the simple rearrangement of 2 or 3 to their
2-bromo analogues because 2-bromophenol was not detected
when these starting materials were treated with heat under Lewis
acid conditions. An alternative mechanism is the involvement
of intermediate (IV) followed by rearrangement to (X) through
s-complexes such as (VIII) and (IX), and finally the subsequent
condensation to lead to 10. Products 11 and 12 may be the
result of bis-condensation of phenol, the hydrodehalogenated
intermediate of the starting bromophenol or bromoanisole. How-
ever, the relatively higher percentage (total 14%) as compared
with the phenol produced from the heat treatment of the respec-
tive starting bromophenol or bromoanisole (5%) suggested that
intermediates such as (III) and (X), respectively, may likely be
involved.
(a)
H
Br
(II)
Br
(I)
Br
2
(11, 8%)
ꢀ
ꢂBr
(a)
OH
OH
OH
OH
OH
(VI)
R
R
ꢂHꢀ
R
R
Br
ꢀ
R
Br
(8, 48%)
Br
H
Br
(9, 22%)
Br
(IV)
H
(V)
OH
OH
OH
OH
OH
Br
(a)
H
Br
(a)
ꢂHꢀ
Br
(a)
R
Br
ꢀ
ꢀ
ꢀ
R
(a)
ꢂBrꢀ
R
R
R
H
(10, 16%)
H
Br
(VII)
H
(X)
(IX)
ꢀ
(VIII)
ꢂBr
ꢂBrꢀ
OH
OH
(11, 4%)
R
R
(XI)
(12, 6%)
m-Bromophenol
OH
OH
OH
R
(13, 22%)
Br
Br
4
Br
R
(XII)
(I)
(9, 2%)
(II)
(VI)
(V)
ꢂBrꢀ
ꢂBrꢀ
In the case of 3-bromophenol 4, the prominence of the major
unrearranged product 8 as compared with the rearranged prod-
uct 13 suggested that the initial acylation at C6 (leading to inter-
mediate (VI)) is preferred over C4 (leading to intermediate
(XII)), which is possibly due to steric factors of the bromo or
electronic factors of the hydroxyl groups, as in the case of 2.
Product 11 may be derived from hydrodelogenated intermediate
(III) through initial acylation at C6 (intermediate (VI)). As 11
wastheonlydehalogenatedproductinthisreaction, participation
of the phenol intermediate is not likely. Product 9 was derived
from intermediate (I) originating from intermediate (VI).
Initial acylation of 2-bromo analogue 5 predominantly occurs
at C4 owing to the para-directing effect of the hydroxyl group
leading to intermediate (XIII), and finally to products 10 or
14 after subsequent condensation. The influence of the para-
directing bromo group in the second condensation is shown
by the five-fold excess of the former as compared with the
latter alternative product. Although less likely owing to the
stronger directing effect of the hydroxyl, product 10 may also
be derived from (X). Rearrangement and hydrodebromination
of this intermediate is rationalized to be the route to prod-
ucts 12 and 11 by the involvement of an intermediate such as
(XI). Preference of 12 over 11 was probably due to the para-
directing effect of the hydroxyl group in (XI). This observation
also suggested that participation of the phenol intermediate is
less important. Product 11 could alternatively be derived from
acylphenol intermediate (III) through intermediates (VI) and
(XIV). The second major product 8 may be achieved through
intermediate (VI) derived from initial ortho-acylation at C6,
followed by rearrangement to intermediate (V) and finally a
(11, 10%)
(III)
(8, 66%)
o-Bromophenol
Br
OH
OH
OH
R
or
R
R
Br
Br
(XIII)
(10, 52%)
(14, 10%)
(XI)
(11, 3% or 12, 15%)
ꢂBrꢀ
ꢂBrꢀ
ꢂBrꢀ
OH
Br
(X)
(IX)
(VIII)
(VII)
(V)
5
R
R
OH
OH
OH
Br
(a)
ꢀ
(V)
(II)
(I)
R
H
Br
(XIV)
ꢂHꢀ
(a)
Br
(9, 3%)
OH
(XV)
(III)
(11, 3%)
(VI)
R
ꢂBrꢀ
Br
(8, 17%)
CO
CO
COOH
ꢁ
ꢁ
R
R
Scheme 2. Proposed mechanistic scheme for the condensation reactions.

824
K. Saha et al.
second intramolecular condensation. Intermediate (XIV) may
also undergo rearrangement and hydrodebromination to inter-
mediate (I), which eventually cyclizes to produce 9. This minor
product may also be achieved through intermediate (V), which
may be derived from (X).
General Procedure for Anthraquinone Synthesis
A mixture of anhydrous aluminium chloride (60 g, 450 mmol)
and sodium chloride (12 g, 205 mmol) was heated until it
completely melted (external temperature, 125–130◦C). Phthalic
anhydride (6.7 g, 45 mmol) and the halogenated benzene deriva-
tive (41 mmol) were mixed well and slowly introduced into the
melt of aluminium chloride and sodium chloride. The mixture
was heated with stirring at 165–170◦C for 45 min. After being
cooled, the reaction mixture was decomposed by adding a mix-
ture of ice and hydrochloric acid. The acidic mixture was then
briefly heated under reflux and filtered after cooling. The crude
residue was extracted with ethyl acetate and the compounds
were purified from the ethyl acetate extract by using column
chromatography.
We investigated further the possible rearrangement in other
halogenated compounds in this reaction by using 4-chlorophenol
6 and 4-iodophenol 7 as the starting materials. Compound 6 gave
only the unrearranged product 15 (47%). From this experiment,
it is evident that halogen migration and hydrodehalogena-
tion did not occur in the case of chlorophenols. However, in
the case of 4-iodophenol 7, only two hydrodeiodinated prod-
ucts, 1-hydroxyanthraquinone 11 and 2-hydroxyanthraquinone
12, were isolated. These products may be derived from phe-
nol resulting from the rapid hydrodeiodination of the starting
4-iodophenol. This is reflected by the relatively lower overall
yield of hydroxyanthraquinones as compared with chloro- or
bromophenol analogues. The higher percentage of product 12
compared with 11 suggested that initial acylation at C4 of phenol
is more predominant than the alternative acylation at C2.
The structures of all the products were supported by their
3-Bromo-1-hydroxyanthraquinone 8
Yellow crystals, mp 188–189◦C. δH 12.63 (s, 1H, 1-OH), 8.33
(m, 2H, H5, H8), 7.96 (d, 1H, J 2.0, H4), 7.86 (m, 2H, H6, H7),
7.52 (d, 1H, J 2.0, H2). δC 188.4 (C9), 181.6 (C10), 163.2 (C1),
135.1 (C7), 134.8 (C6), 134.3 (C14), 133.3 (C12), 133.2 (C11),
131.8 (C13), 127.9 (C8), 127.3 (C5), 127.1 (C2), 123.1 (C4),
115.3 (C3). νmax/cm−1 3437, 1674, 1638, 1591. m/z (EI) 304
(66%, [M+ + 2]), 302 (63, [M+]), 276 (7), 274 (6), 248 (11),
246 (14), 223 (18), 195 (15), 167 (21), 139 (100), 113 (14),
97 (33), 83 (29), 69 (96). High resolution electron impact mass
spectrometry (HREIMS) m/z (%): 303.9558 ([M+], 97, required
304.1263), 301.9575 ([M+], 100, required 302.1284).
spectroscopic data. Along with UV, IR, mass, 1H NMR, and 13
C
NMR spectra, the structures were also confirmed by their corre-
lation spectroscopy, heteronuclear single-quantum correlation,
and heteronuclear multiple bond correlation (HMBC) spectra
(see Accessory Publication).
Conclusions
4-Bromo-1-hydroxyanthraquinone 9
From these observations, it appears that during Lewis acid-
catalyzed Friedel–Crafts bis-acylation of halophenols, acyla-
tion of the aromatic ring leading to halogen rearrangement,
hydrodehalogenation or both competes with protonation, lead-
ing to the observed outcomes. The preference between two
pathways depends on the nature of the aromatic ring substi-
tution. Furthermore, whereas acylation of chlorophenol did
not lead to rearranged product, acylation of bromophenols
and bromoanisole led to rearranged and minor hydrodehalo-
genated products. Under the same conditions, iodophenol led
to hydrodehalogenated anthraquinones. Mechanisms other than
that proposed may also occur to account for the different product
ratios, but it is not possible to determine their extent from the
current experiments.
Yellow-orange needles, mp 195–196◦C. δH 13.29 (s, 1H, 1-OH),
8.30 (m, 2H, H5, H8), 7.90 (d, 1H, J 9.0, H3), 7.83 (m, 2H, H6,
H7), 7.17 (d, 1H, J 9.0, H2). δC 188.3 (C9), 181.4 (C10), 163.23
(C1), 144.1 (C3), 135.4 (C7), 134.3 (C12), 134.3 (C6), 132.3
(C11), 130.2 (C14), 128.0 (C8), 126.8 (C5), 125.4 (C2), 117.9
(C13), 113.4 (C4). νmax/cm−1 3438, 1670, 1636, 1590. m/z (EI)
304 (93%, [M+ + 2]), 302 (100, [M+]), 276 (14), 274 (15), 248
(20), 246 (21), 223 (5), 195 (5), 167 (6), 139 (69), 113 (12), 97
(6), 69 (28). HREIMS m/z (%): 303.9560 ([M+], 98, required
303.9558), 301.9575 ([M+], 100, required 301.9579).
3-Bromo-2-hydroxyanthraquinone 10
Yellow amorphous solid, mp 262–263◦C. δH 12.00 (br s, 1H,
2-OH), 8.24 (s, 1H, H1), 8.16 (m, 2H, H5, H8), 7.91 (m, 2H,
H6, H7), 7.65 (s, 1H, H1). δC 182.8 (C10), 181.2 (C9), 160.4
(C2), 135.4 (C6), 135.0 (C7), 134.9 (C13), 133.7 (C11), 133.6
(C12), 132.9 (C4), 127.4 (C5 and C8), 126.6 (C14), 117.5 (C3),
113.5 (C1). νmax/cm−1 3413, 1668, 1572. m/z (EI) 304 (98%,
[M+ + 2]), 302 (100, [M+]), 276 (19), 274 (18), 248 (17), 246
(18), 223 (15), 195 (18), 167 (21), 139 (89), 123 (14), 83 (36), 69
(94), 50 (25). HREIMS m/z (%): 303.9560 ([M+], 98, required
303.9558), 301.9582 ([M+], 100, required 301.9579).
Experimental
General
Melting points were determined on a hot-stage melting point
apparatus, XSP-12 500X, and are uncorrected. UV spectra were
recorded on a CARY 100 Conc UV-visible spectrophotometer
in CHCl3 or MeOH. IR spectra were recorded on a Perkin–
Elmer RXI Fourier transform (FT) IR spectrometer as KBr
disks. Mass spectra were measured on a Finnigan Mat SSQ 710
spectrometerwithionizationinducedbyelectronimpactat70 eV.
NMR spectra were recorded in CDCl3 or [D6]DMSO using a
Varian 500 MHz NMR spectrometer. Column chromatography
was performed on silica gel 60 Merck 9385 (230–400 mesh
American Society for Testing and Materials (ASTM)). HPLC
was carried out with a JASCO PU-2086 Plus pump, equipped
with a UV-2077 Plus detector, using an Inertsil ODS-3V
(5 µm; 4.6 i.d. × 150 mm) column, and CH3CN/H2O (gradient:
0–10 min(100:0);10–20 min(100:0–45:55);20–22 min(45:55);
22–27 min (45:55–0:100)).
1-Hydroxyanthraquinone 11[20]
Yellow-orange needles, mp 190–191◦C. δH 12.64 (s, 1H, 1-OH),
8.34 (m, 2H, H5, H8), 7.86 (dd, 1H, J 7.5, 1.0, H4), 7.84 (m, 2H,
H6, H7), 7.71 (t, 1H, J 8.0, 7.5, H3), 7.34 (dd, 1H, J 8.0, 1.0, H2).
δC 188.9 (C9), 182.7 (C10), 162.8 (C1), 137.0 (C3), 134.9 (C7),
134.4 (C6), 133.9 (C12), 133.7 (C14), 133.5 (C11), 127.7 (C8),
127.2 (C5), 124.6 (C2), 119.8 (C4), 116.4 (C13). νmax/cm−1
3436, 1674, 1638, 1592. m/z (EI) 224 (100%, [M+]), 196 (19),
168 (36), 139 (51), 113 (7), 98 (10), 84 (13), 70 (44), 50 (19).

Halophenol Rearrangement
825
2-Hydroxyanthraquinone 12[21]
Accessory Publication
Yellow amorphous solid, mp 298–299◦C. δH 11.08 (br s, 1H, 2-
OH), 8.17 (m, 2H, H5, H8), 8.10 (d, 1H, J 8.5, H4), 7.90 (m, 2H,
H6, H7), 7.51 (d, 1H, J 2.5, H1), 7.25 (dd, 1H, J 8.5, 2.5, H3). δC
183.4 (C9), 181.9 (C10), 163.8 (C2), 135.9 (C13), 135.3 (C7),
134.7 (C6), 133.9 (C12), 133.8 (C11), 130.6 (C4), 127.3 (C8),
127.3 (C5), 125.9 (C14), 122.3 (C3), 112.9 (C1). νmax/cm−1
3370, 1672, 1578. m/z (EI) 224 (100%, [M+]), 196 (35), 168
(35), 139 (78), 113 (9), 98 (7), 84 (12), 63 (21).
UV, IR, mass, 1H NMR, and 13C NMR spectra, and the structures
that were also confirmed by their correlation spectroscopy,
heteronuclear single-quantum correlation, and HMBC spectra
are available from the journal’s website.
Acknowledgements
The authors thank University Putra Malaysia and the Ministry of Science,
Technology and Innovation for the funds provided under the Scientific
Advancement Grant Allocation (SAGA) research funding program.
1-Bromo-3-hydroxyanthraquinone 13
Yellow amorphous solid, mp 180–181◦C. δH 11.50 (br s, 1H, 3-
OH), 8.14 (m, 2H, H5, H8), 7.90 (m, 2H, H6, H7), 7.59 (d, 1H,
J 2.5, H4), 7.46 (d, 1H, J 2.5, H2). δC 182.3 (C10), 180.6 (C9),
162.5 (C3), 138.2 (C14), 135.5 (C6), 134.8 (C11), 134.5 (C7),
132.8 (C12), 128.1 (C2), 127.6 (C5), 126.9 (C8), 124.2 (C1),
122.9 (C13), 114.3 (C4). νmax/cm−1 3393, 1655, 1576. m/z (EI)
304 (22%, [M+ + 2]), 302 (24, [M+]), 276 (11), 274 (11), 248
(8), 246 (9), 223 (6), 195 (14), 167 (17), 139 (100), 113 (13), 87
(12), 69 (23), 50 (38). HREIMS m/z (%): 303.9563 ([M+], 99,
required 303.9558), 301.9581 ([M+], 100, required 301.9579).
References
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S. Ngouela, J. C. N. Assob, C. Vonthron-Senecheau, P. A. Fokou,
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1-Bromo-2-hydroxyanthraquinone 14
Yellow crystals, mp 184–185◦C. δH 11.90 (br s, 1H, 2-OH), 8.12
(m, 3H, H5, H8, H4), 7.88 (m, 2H, H6, H7), 7.38 (d, 1H, J
8.5, H3). δC 182.7 (C9), 181.5 (C10), 161.4 (C2), 135.0 (C7),
134.9 (C12), 134.8 (C6), 133.1 (C13), 132.7 (C11), 129.5 (C4),
128.1 (C14), 127.6 (C8), 126.7 (C5), 120.8 (C3), 110.3 (C1).
νmax/cm−1 3548, 1675, 1589. m/z (EI) 304 (90%, [M+ + 2]),
302 (100, [M+]), 276 (30), 274 (28), 248 (18), 246 (19), 223
(16), 195 (14), 167 (19), 139 (69), 124 (14), 91 (7), 69 (37).
HREIMS m/z (%): 303.9560 ([M+], 97, required 303.9558),
301.9579 ([M+], 100, required 301.9579).
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S. M. Mohamed, A. S. H. Ho, N. H. Lajis, Pharm. Biol. 2000, 38,
298. doi:10.1076/1388-0209(200009)38:4;1-A;FT298
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4-Chloro-1-hydroxyanthraquinone 15
Yellow needles, mp 190–191◦C. δH 13.28 (s, 1H, 1-OH), 8.32 (m,
2H, H5, H8), 7.84 (m, 2H, H6, H7), 7.69 (d, 1H, J 9.0, H3), 7.27
(d, 1H, J 9.0, H2). δC 188.5 (C9), 181.5 (C10), 162.6 (C1), 140.9
(C3), 135.4 (C7), 134.6 (C12), 134.2 (C6), 132.3 (C11), 128.9
(C4), 127.9 (C8), 126.9 (C5), 126.7 (C14), 125.5 (C2), 117.4
(C13). νmax/cm−1 3455, 1640. m/z (EI) 260 (35%, [M+ + 2]),
258 (100, [M+]), 232 (10), 230 (26), 204 (11), 202 (33), 167
(10), 139 (52), 113 (6), 87 (5), 69 (6), 50 (3). HREIMS m/z (%):
260.0056 ([M+], 33, required 260.0054), 258.0082 ([M+], 100,
required 258.0084).
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doi:10.1016/S0040-4039(00)87187-7
General Procedure for Halophenol Rearrangement
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Halophenol or haloanisole (1.16 mmol) was introduced into a
melt of AlCl3 (1.55 g, 11.6 mmol) and NaCl (0.31 g, 5.3 mmol)
at 120–130◦C (external temperature). The mixture was heated
with stirring for 10 min at that temperature. After cooling, the
melt was decomposed by the addition of a mixture of ice and
hydrochloric acid. The acidic mixture was briefly heated under
reflux and then extracted with ethyl acetate.
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