Solvent affected facile synthesis of hydroxynaphthyl ketones: Lewis acids promoted Friedel-Crafts and demethylation reaction

Article abstract of DOI:10.1080/00397910701263692

Hydroxynaphthyl ketones were obtained with high yields under very mild conditions in the presence of AlCl3 via Friedel-Crafts acylation and demethylation from naphthyl ethers. Several Lewis acids were tested, and AlCl3 was the most efficient catalyst. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701263692

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Synthetic Communications , 37: 1595–1601, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701263692
Solvent Affected Facile Synthesis of
Hydroxynaphthyl Ketones: Lewis Acids
Promoted Friedel–Crafts and
Demethylation Reaction
Wan-mei Li, Hu-qin Lai, Zhong-hua Ge, Cheng-rong Ding,
and Ying Zhou
College of Chemical Engineering and Materials Science, Zhejiang
University of Technology, Hangzhou, China
Abstract: Hydroxynaphthyl ketones were obtained with high yields under very mild
conditions in the presence of AlCl via Friedel–Crafts acylation and demethylation
3
from naphthyl ethers. Several Lewis acids were tested, and AlCl
efficient catalyst.
3
was the most
Keywords: demethylation, Friedel–Crafts, hydroxynaphthyl ketones, Lewis acids
Hydroxynaphthyl ketones (2) were usually prepared from the corresponding
naphthyl esters via a Fries-rearrangement reaction in the presence of Lewis
[1]
acid (Scheme 1). Although the yields were good, the deacylation product
3) inevitably was formed. The by-products (3) were difficult to isolate from
the desired products.
(
The direct acylation of naphthol in the presence of catalyst was possi-
1a,1f,1g,2]
but in fact the reactions proceeded with acylation of hydroxyl
[
ble,
followed by Fries rearrangement in many cases. Herein we report a facile and
efficient method for the preparation of hydroxynaphthyl ketones from
naphthyl ethers with acylating reagents catalyzed by Lewis acid.
Received July 21, 2006
Address correspondence to Hu-qin Lai, College of Chemical Engineering and
Materials Science, Zhejiang University of Technology, Hangzhou 310014, China.
E-mail: laihuqin@zjut.edu.cn
1
595

1
596
W.-m. Li et al.
Scheme 1.
Initially, several Lewis acids were investigated in the reaction
Scheme 2), and the results are shown in Table 1. Data showed that
anhydrous AlCl (entry 1), TiCl (entry 11), and BF (entry 8) were the
(
3
4
3
better catalysts. In these cases, the acetylated and demethylated product
2a) was isolated in good yield. Acetylation product (3a) was formed in
about 20% yields. Other Lewis acids such as SnCl , ZnCl , and FeCl
(
4
2
3
showed low activity in terms of demethylating. The acylating reagent
obviously affected the results; when active acetyl bromide was used instead
of acetyl chloride in the presence of AlCl or BF , only a trace of 3a was
3
3
detected, and 2a was obtained in very high yields (entry 2 and 8). AlBr3
showed excellent reactivity in this reaction when acetyl chloride was used
as the acylating reagent (entry 7); the same results were obtained with the
use of AlCl and acetyl bromide. In this reaction condition, we suppose that
3
the halogen would be transformed between the catalyst and acetylating
reagent (Scheme 3).
However, we found the solvent affected the results greatly. The ratio of
two products could be reversed in different solvents. CS and hexane were
2
suitable for demethylation reaction to obtain 2a. Product 3a was formed in
40% yield when CH NO was used as the solvent. If the reaction was
carried out in CH Cl as well as CHCl , 3a was the main product, contami-
3 2
2
2
3
nated with a very small amount of 2a. In addition, the amount of AlCl3
should not be fewer than 2.0 equiv.; otherwise the demethylation reaction
would not proceed thoroughly, and acetylated product 3a was the major
product.
Thus in the presence of AlCl and acetyl bromide, several hydroxy-
3
naphthyl ketones were prepared from naphthyl ethers (Scheme 4, Table 2).
Obviously, a-ethers as well as b-ethers could be converted to corresponding
Scheme 2.

Hydroxynaphthyl Ketones
1597
Table 1. Lewis acid–catalyzed reactions of naphthyl ethers with acylating reagents
2
(yield %)
a
3a
(yield %)
a
a
Entry
LA
X
Solvent
1
2
3
4
5
6
7
8
9
AlCl
AlCl
3
3
Cl
Br
Cl
Cl
Cl
Cl
Cl
CS
CS
2
75
94
71
58
8
19
trace
20
2
AlCl3
AlCl3
Hexane
CH NO
40
3
2
AlCl
AlCl
3
3
CHCl
CH
3
89
93
2
Cl
2
5
AlBr3
BF
SnCl
ZnCl2
TiCl
CS2
95
68 (93 )
Trace
b
23 (2 )
b
b
3
Cl (Br )
Cl
CS
CS
2
4
2
33
38
73
31
22
58
55
22
62
71
1
1
1
1
0
1
2
3
Cl
Cl
CS2
4
CS
CS
2
FeCl
AlCl
3
c
3
Cl
Br
2
CS2
a
b
c
Isolated yields based on ethers.
Acetyl bromide was used instead of acetyl chloride.
.0 equiv. of AlCl was used.
1
3
products in high yields. Furthermore, the reaction also proceeded well when
diether was the substrate (Scheme 5). It was clear that both HBr and AlCl
3
[3]
were reacted as mild demethylation reagents.
In contrast, the preparation of compound 2i by normal Fries-rearrange-
ment reaction from the corresponding ester was unsuccessful. An unidentified
Scheme 3.
Scheme 4.

1
598
W.-m. Li et al.
Table 2. Synthesis of hydroxynaphthyl ketones in carbon disulfide
Yield
a
(%)
2
Entry
1
Ether
R
Product
CH
CH
CH
Ph
3
3
3
94
93
94
90
96
2
3
4
5
CH
CH
2
2
CH
2
CH
3
3
6
7
CH
Ph
CH
2
95
89
8
CH3
97
a
Isolated yields based on naphthyl ethers.
complex was obtained (Scheme 6). Thus the present work has an advantage
compared with the normal synthetic route.
In conclusion, with high yields, simple operation, and mild reaction con-
ditions, the work described gives a useful method for the preparation of hydro-
xynaphthyl ketones. The preparation and procedure would be suitable for a
large scale, too.

Hydroxynaphthyl Ketones
1599
Scheme 5.
EXPERIMENTAL
All reagents used are commercially available. Melting points were uncor-
1
rected. H NMR spectra was recorded on a Varian 400-MHz instrument
using CDCl as the solvent with TMS as an internal standard. IR spectra
3
were recorded on an Avatar-370. Mass spectra were test by a Thermo
Finnagan LCQ Advantage instrument. Microanalysis was carried out on a
Carlo-Erba 1106 instrument.
General Experimental Procedure
To solution of naphthyl ether (0.1 mol) and acetyl bromide (0.12 mol, 14.6 g)
in CS (50 mL) at 08C, anhydrous AlCl (29.3 g) was added in several
2
3
portions, very carefully holding the temperature under 58C. After completion,
the mixture was heated to reflux and stirred for additional 2 h. Then the solvent
was evaporated, and a gummy mixture was obtained. The ice water was
poured into the mixture, and then concentrated HCl (50 mL) was added sub-
sequently. The suspension was stirred vigorously for 10 min. The crude
desired products were obtained as straw-yellow solids after filtration; in
most cases the purity was higher than 95%.
Further purification should be carried out as following: The crude product
obtained was treated with an appropriate volume of 20% NaOH to obtain a
yellow aqueous solution, then filtered. The filtrate was neutralized with HCl
Scheme 6.

1
600
W.-m. Li et al.
to pH ¼ 5, and white solid precipitated. The pure (99% by HPLC) product was
collected.
Data
[
1a]
21
1
2-Acetyl-1-naphthol (2a):
IR (nmax/cm ): 3310, 1678; H NMR (d,
CDCl ): 2.61 (s, 3H), 7.20 (d, J ¼ 8.4 Hz, 1H), 7.50–7.57 (m, 1H), 7.62–
3
7
.69 (m, 1H), 7.71 (d, J ¼ 8.4 Hz, 1H), 7.79 (d, J ¼ 8.0 Hz, 1H), 8.44
(
d, J ¼ 8.4 Hz, 1H), 15.12 (s, 1H).
[
4]
21
1
2
-Propionyl-1-naphthol (2b): IR (nmax/cm ): 3358, 1698; H NMR (d,
CDCl ): 1.24 (t, J ¼ 7.2 Hz, 3H), 2.85 (q, J ¼ 7.2 Hz, 2H), 7.21
3
(
d, J ¼ 8.4 Hz, 1H), 7.52–7.62 (m, 1H), 7.64–7.69 (m, 1H), 7.70
d, J ¼ 8.4 Hz, 1H), 7.78 (d, J ¼ 8.0 Hz, 1H), 8.45 (d, J ¼ 8.4 Hz, 1 H),
(
1
1.48 (s, 1H).
[
5]
21
1
2
-Butyryl-1-naphthol (2c): IR (nmax/cm ): 3338, 1686; H NMR (d,
CDCl ): 1.11 (t, J ¼ 7.6 Hz, 3H), 1.77 (m, 2H), 2.91 (t, J ¼ 7.6 Hz, 2H),
3
7
.22 (d, J ¼ 8.4 Hz, 1H), 7.51–7.60 (m, 1H), 7.64–7.68 (m, 1H), 7.71
(d, J ¼ 8.4 Hz, 1H), 7.80 (d, J ¼ 8.0 Hz, 1H), 8.46 (d, J ¼ 8.4 Hz, 1 H),
1
2.41 (s, 1H).
[
1e]
21
IR (nmax/cm ): 3402, 1656; H NMR (d,
1
2-Benzoyl-1-naphthol (2d):
CDCl ): 7.21 (d, 1H, J ¼ 8.8 Hz), 7.61–7.49 (m, 5H), 7.64 (t, 1H,
3
J ¼ 8 Hz), 7.71 (d, 2H, J ¼ 8 Hz), 7.75 (d, 1H, J ¼ 8 Hz), 8.52 (d, 1H,
J ¼ 8 Hz), 14.55 (s, 1H).
[
1b]
21
IR (nmax/cm ): 3322, 1706; H NMR (d,
1
1-Acetyl-2-naphthol (2e):
CDCl ): 2.83 (s, 3H), 7.11 (d, J ¼ 8.4 Hz, 1H), 7.35–7.39 (m, 1H), 7.52–
3
7
.56 (m, 1H), 7.75 (d, J ¼ 8.4 Hz, 1H), 7.85 (d, J ¼ 8.4 Hz, 1H), 8.05
(
d, J ¼ 8.4 Hz, 1H), 13.1 (s, 1H).
[
5]
21
1
1
-Propionyl-2-naphthol (2f): IR (nmax/cm ): 3398, 1712; H NMR (d,
CDCl ): 1.28 (t, J ¼ 7.6 Hz), 2.88 (m, 2H), 7.11 (d, J ¼ 8.4 Hz, 1H), 7.35–
3
7
.39 (m, 1H), 7.52–7.56 (m, 1H), 7.75 (d, J ¼ 8.4 Hz, 1H), 7.85
(
d, J ¼ 8.4 Hz, 1H), 8.05 (d, J ¼ 8.4 Hz, 1H), 13.1 (s, 1H).
[
6]
21
1
1
-Benzoyl-2-naphthol (2g): IR (nmax/cm ): 3350, 1647; H NMR (d,
CDCl ): 7.15 (t, J ¼ 8.0 Hz, 1H), 7.31–7.22 (m, 3H), 7.40 (t, J ¼ 7.6 Hz,
3
2
H), 7.55 (t, J ¼ 7.6 Hz, 1H), 7.62 (d, J ¼ 8.0 Hz, 2H), 7.74 (d, J ¼ 8.0 Hz,
1
H), 7.92 (d, J ¼ 8.8 Hz, 1H), 13.10 (s, 1H).
[
7]
21
1
4
-Methyl-2-acetyl-1-naphthol (2h): IR (nmax/cm ): 3408, 1689; H
NMR (d, CDCl ): 2.61 (s, 3H), 2.65 (s, 3H), 7.55–7.58 (m, 1H), 7.64–7.69
3

Hydroxynaphthyl Ketones
1601
(
m, 1H), 7.78 (d, J ¼ 8.4 Hz, 1H), 7.83 (d, J ¼ 8.0 Hz, 1H), 8.41
d, J ¼ 8.4 Hz, 1H), 10.56 (s, 1H).
(
2
,3-Diacetyl-4-hydroxyl-1-naphthol (2i): mp: 201–2028C, gray powder
21
(will turn dark after long exposure in moist air); IR (nmax/cm ): 3398,
1
1
697; H NMR (d, CDCl ): 2.66 (s, 6H), 7.95–7.99 (m, 2H), 8.26–8.30
3
1
3
m, 2H), 11.02 (s, 2H); C NMR (d, CDCl ): 211.3, 154.8, 134.8, 130.7,
(
3
-
1
C H O : C, 68.85; H, 4.95; found: C, 68.78; H, 4.89.
25.4, 119.1, 31.1; ESI- MS (m/z): 243.1 (M-H) . Anal. calcd. for
1
4 12 4
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