The reaction of arylacetones with boron tribromide

Article abstract of DOI:10.1055/s-1999-3572

Treatment of arylacetones 1 with boron tribromide gives 1,3-dimethyl-2- arylnaphthalenes 3 in fair to good yields by a tandem aldol condensation- intramolecular cyclization. This reaction is limited to the electron-rich arylacetones. In the case of methox

Full text of DOI:10.1055/s-1999-3572

PAPER
1651
The Reaction of Arylacetones with Boron Tribromide
Romain Dupont, Philippe Cotelle*
Laboratoire de Chimie Organique Physique associé au CNRS, ENSCL, Université de Lille 1, F-59655 Villeneuve d’Ascq, France
Fax: +33(3)20 33 63 09; E-mail: Philippe.Cotelle@univ-lille1.fr
Received 12 February 1999, revised 11 May 1999
R1
R1
Abstract: Treatment of arylacetones 1 with boron tribromide gives
1,3-dimethyl-2-arylnaphthalenes 3 in fair to good yields by a tan-
dem aldol condensation-intramolecular cyclization. This reaction is
limited to the electron-rich arylacetones. In the case of methoxyphe-
nylacetones, a demethylation occurs leading to 1,3-dimethyl-2-hy-
droxyphenylnaphthols. Other cyclization may occur for
orthomethoxyphenylacetones leading to intramolecular acetal 4b or
5-, 6- or 7-hydroxy-2-methylbenzo[b]furans 6n–p. In the case of the
1-naphthylacetone, a bromination reaction of the phenanthrene 3i
occurs leading to bromophenanthrene 5i.
R2
R3
R2
R3
O
O
BBr2
R4
R4
1 enolate form
1 keto form
R1
R2
R1
R2
Key words: tandem aldol condensation-intramolecular cyclization,
boron tribromide, 1,3-dimethyl-2-phenylnaphthalenes, 2-methyl-
benzo[b]furans
R3
R3
R1
R1
R2
R3
R2
R3
R4
R4
OBBr2
O
2
Highly substituted phenylnaphthalenes are common fea-
tures of numerous biologically significant products and
pharmaceuticals1 and new or improved methods for their
regioselective construction have received significant at-
tention in recent years.2 The most important reported
routes to 2-phenylnaphthalenes include the following: (i)
Suzuki coupling3 of the appropriate 2-naphthylboronic
acid with iodobenzenes; (ii) Stille coupling3 of trifluorom-
ethylsulfonyloxynaphthalene for example with arylstan-
nates; (iii) Katritzky annulation.2g
R4
R4
R1
R1
R2
R2
R1
R1
R2
R3
R2
R3
R3
R3
H
R4
R4
OBBr2
As a part of our studies on the synthesis of new biological-
ly active polyhydroxylated compounds, we have devel-
oped a new convenient synthesis of polyhydroxylated 2-
phenylnaphthalenes in a one pot procedure from mono- or
dimethoxyphenylacetones and boron tribromide.4 The ex-
tension of this reaction to arylethanals has revealed re-
markable aspects of product differentiation,5 i.e.,
formation of 2-phenylnaphthalene from phenylethanal
and epoxydibenzo[a,e]cyclooctenes from activated aryle-
thanals.
R4
R4
3
Scheme 1
ably due to the deactivating effect of the fluorine atom. 3-
Fluorophenylacetone 1f gave the best yield of this series
due to para orientation of the fluorine atom in the cycliza-
tion.
The intramolecular reaction was also highly regioselec-
tive as attested by the formation of only one product from
1c and 1f. Nevertheless, byproducts might be obtained in
the cases of 1b and 1i; the former compound gave an in-
tramolecular acetal 4b (Scheme 2) and the latter a bromi-
nated phenanthrene 5i (Scheme 3). Since phenanthrene
treated with boron tribromide was totally recovered, we
supposed that the bromination is due to the activating ef-
fect of the methyl and the naphthyl groups.
We now report the generalization of the reaction of ary-
lacetones with boron tribromide in order to clearly define
the scope and the limitation of this reaction.
When the aromatic ring was unsubstituted or substituted
by an electron-donating group (OCH3, CH3, F) 1,3-dime-
thyl-2-arylnaphthalenes 3 were obtained in moderate to
high yields (Scheme 1, Tables 1 and 2, compounds 1a–i).
Boron tribromide reacted with phenylacetone to give a bo-
ron enolate which reacted stereoselectively with another
molecule of phenylacetone to give the aldol condensation
product 2. Compound 2 underwent an intramolecular re-
action to give 3. As expected methyl or methoxyphenylac-
etones (1b–d, 1h) gave 3 in high yields whereas
fluorophenylacetones (1e–g) gave 3 in lower yields prob-
When the aromatic ring was substituted by an electron-
withdrawing group (CF3 or NO2), the intramolecular cy-
clization was totally inhibited. Nevertheless, in the case of
3-trifluoromethylphenylacetone 1j, the intermediate 2j,
obtained in fair yield, was the sole isolated product. The
1H spectrum of the crude product of the reaction revealed,
Synthesis 1999, No. 9, 1651–1655 ISSN 0039-7881 © Thieme Stuttgart · New York

1652
R. Dupont, P. Cotelle
PAPER
Table 1 Reaction of Arylacetones 1 with Boron Tribromide
Starting
material
R1
R2
R3
R4
Product
R1
R2
R3
R4
Yielda in 3
1a
1b
1c
1d
H
OCH3
H
H
F
H
H
H
CH=CH-CH=CH
H
NO2
H
H
OCH3
OCH3
OCH3
H
H
H
OCH3
H
H
F
H
H
H
H
H
OCH3
H
H
F
CH3
H
H
H
H
NO2
H
OCH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OCH3
H
3a13
3b
3c
3d
3e
3f
3g
3h
3i
2j
–
–
–
H
OH
H
H
F
H
H
H
H
H
OH
H
H
F
H
H
H
OH
H
H
F
CH3
H
H
H
H
H
H
H
H
H
H
H
H
90%
61%b
81%
83%
31%
62%
26%
92%
30%c
15%
0%
0%
0%
22%
16%
17%
77%
1e
1f14
1g
H
H
1h
1i15
1j
CH=CH-CH=CH
H
CF3
H
NO2
H
OCH3
H
H
CF3
1k12
1l16
1m17
1n9
1o
6n
6o
6p
3q
–
–
–
H
OH
H
H
H
OH
H
H
H
OH
H
1p18
1q
OCH3
OCH3
OH
OH
a Yields of purified compounds.
b 3b was obtained with 16% of 4b.
c 3i was obtained with 35% of 5i.
thylation. As expected, the total demethylation occured
for 1q, whereas 1n–p led to a mixture of partially and to-
tally demethylated products. The main products obtained
from 1n–p were 7-, 6- or 5-hydroxy-2-methylben-
zo[b]furans 6n–p6-8 respectively in about 20% yield
(Scheme 4). In an attempt to obtain the completely deme-
thylated phenylnaphthalenes 3n–p, 1n–p were treated
with an excess of boron tribromide (10 equiv) under re-
flux overnight. Unfortunately, the attempts to isolate or-
ganic material were unsuccessful.
OH
O
O
O
OH
4b
Scheme 2
R4
R3
R4
R3
O
BBr3, CH2Cl2, rt, 1h
O
O
OCH3
R2
1n-p
R2
6n-p
BBr3, CH2Cl2, rt, 1h
R
1i
3i: R=H
5i: R=Br
Scheme 4
Scheme 3
As a conclusion, the reaction of activated arylacetones
with boron tribromide gives an efficient route to substitut-
ed 1,3-dimethyl-2-phenylnaphthalenes. The reaction pro-
ceeds by the mechanism depicted in Scheme 1 and the
intermediate 2 has been isolated in the case of the deacti-
vated arylacetone 1j. The limiting step is probably the in-
tramolecular cyclization since substituted 1,3-dimethyl-2-
phenylnaphthalenes cannot be obtained from arylacetones
with an electron-withdrawing group. We have shown that
three side-reactions may occur: (i) when a hydroxy group
was formed during the reaction in ortho position, an in-
tramolecular acetal may be obtained, (ii) an additional hy-
droxy group to an ortho hydroxy group favored the
in addition to 2j, the presence of several peaks at 3.5–4.5
ppm and 1.5–2.5 ppm. These peaks may be attributed to
oligomers of the aldol condensation. Nitrophenylacetones
1k–m gave a large amount of polymers (All attempts to
isolate organic material were unsuccessful).
Finally, since our main goal was the obtention of polyhy-
droxylated phenylnaphthalenes, we treated dimethox-
yphenylacetones 1n–q with boron tribromide. In these
cases, we used one additional equivalent of boron tribro-
mide by methoxy group in order to effect the total deme-
Synthesis 1999, No. 9, 1651–1655 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Reaction of Arylacetones with Boron Tribromide
1653
Table 2 Physical and Analytical Data of all Compoundsa
Prod-
uct
mp (°C),
Solvent
1H NMR (200 MHz, TMS)
d, J (Hz)
13C NMR (50 MHz, TMS)
d
MS m/z
(%)
3a
3b
4b
3c
oil13
69–71b
oil
(CDCl3): 2.18 (3 H, d, 4J = 0.9), 2.41 (3 H, s), (CDCl3): 16.3 (q), 21.8 (q), 124.2 (d), 125.0 232 (100), 217
7.25 (2 H, m), 7.50 (5 H, m), 7.63 (1 H, br s), (d), 125.3 (d), 125.6 (d), 126.5 (d), 127.5 (d), (37), 216 (15),
7.73 (1 H, m), 8.07 (1 H, m)
128.2 (d), 129.2 (d), 131.1 (s), 131.2 (s),
132.7 (s), 134.3 (s), 140.1 (s), 141.5 (s)
202 (14), 115
(11), 108 (16),
101 (13)
(CDCl3): 2.21 (3 H, d, 4J = 0.9), 2.43 (3 H, s), (CDCl3): 16.4 (q), 21.5 (q), 109.0 (d), 115.3 264 (100), 249
6.85 (1 H, dd, 3J = 7.4, 4J = 1.2), 7.08 (3 H,
m), 7.33 (1 H, dd, 3J = 8.6, 3J = 7.4), 7.37
(d), 117.2 (d), 120.2 (d), 120.7 (d), 124.3 (d), (45), 234 (12),
125.4 (s), 127.0 (s), 129.1 (d), 130.1 (d),
232 (11), 149
(32), 101 (12)
(1 H, dd, 3J = 8.6, 4J = 2.9), 7.63 (1 H, ddd, 132.8 (s), 133.7 (s), 133.9 (s), 134.6 (s),
3J = 8.6, 4J = 1.2, 5J = 0.9), 8.05 (1 H, br s)
151.3 (s), 152.4 (s)
(CDCl3): 1.87 (3 H, s), 2.59 (3 H, s), 3.45 (1 (CDCl3): 14.0 (q), 28.3 (q), 43.5 (t), 86.6 (s), 264 (81), 249
H, d, 2J = 15.4), 3.66 (1 H, d, 2J = 15.4), 6.88 109.5 (d), 110.7 (d), 119.9 (d), 120.4 (d),
(100), 221
(22), 157 (32),
131 (23), 77
(22)
(2 H, m), 7.20 (6 H, m)
122.2 (d), 123.2 (d), 125.1 (d), 126.6 (d),
128.2 (s), 128.8 (s), 130.8 (s), 149.9 (s),
153.9 (s), 158.3 (s)
158–160, CH2Cl2 (CDCl3): 2.14 (3 H, d, 4J = 1.0), 2.36 (3 H, s), (DMSO-d6): 16.2 (q), 21.5 (q), 108.7 (d),
264 (100), 249
(13), 231 (9)
6.66 (1 H, dd, 4J = 2.5, 4J = 1.6), 6.69 (1 H,
ddd, 3J = 6.8, 4J = 1.5, 4J = 1.0), 6.84 (1 H,
113.6 (d), 116.2 (d), 117.6 (d), 119.9 (d),
124.0 (d), 125.4 (s), 125.9 (d), 129.4 (d),
ddd, 3J = 8.2, 4J = 2.5, 4J = 1.0), 7.10 (2 H, m), 130.4 (s), 133.8 (s), 133.9 (s), 136.9 (s),
7.31 (1 H, dd, 3J = 8.2, 3J = 7.4), 7.42 (1 H,
br s), 7.89 (1 H, dd, 3J = 9.1, 5J = 0.7)
142.5 (s), 154.9 (s), 157.3 (s)
3d
3e
210, Acetone
(DMSO-d6): 2.02 (3 H, br s), 2.19 (3 H, s),
(DMSO-d6): 16.4 (q), 21.5 (q), 105.9 (d),
264 (100), 249
(13), 149 (18),
107 (56)
6.84 (2 H, d, 3J = 8.5), 6.94 (2 H, d, 3J = 8.5), 115.1 (d), 117.7 (d), 125.3 (d), 126.9 (s),
7.03 (1 H, dd, 3J = 8.7, 4J = 2.2), 7.17 (1 H,
dd, 4J = 2.2, 5J = 0.9), 7.47 (1 H, br s), 7.65
129.0 (d), 129.1 (s), 130.1 (d), 130.7 (s),
131.6 (s), 132.3 (s), 140.0 (s), 154.9 (s),
(1 H, d, 3J = 8.7), 9.40 (1 H, br s), 9.60 (1 H, 156.0 (s)
br s)
oil
(CDCl3): 2.32 (3 H, d, 4J = 0.65), 2.50 (3 H, (CDCl3): 16.7 (q), 21.7 (q), 109.3 (d, 2J =
s), 7.00–7.55 (5 H, m), 7.77–7.97 (2 H, m),
8.04 (1 H, s)
268 (100), 267
(5), 253 (23),
252 (11), 251
19.7), 115.2 (s, 2J = 22.0), 115.8 (d, 2J =
22.3), 118.38 (d, 3J = 7.4), 118.39 (s, 2J =
19.3), 120.3 (d, 4J = 4.1), 124.1 (s, 4J = 3.7), (24), 233 (21)
124.25 (d, 4J = 3.7), 124.7 (s, 3J = 7.4), 124.9
(s, 4J = 1.9), 127.9 (s, 3J = 8.2), 129.3 (d, 3J =
7.8), 130.7 (d, 3J = 4.5), 131.5 (d, 4J = 3.7),
158.8 (s, 1J = 244.9), 159.6 (s, 1J = 244.5)
3f
50
(CDCl3): 2.19 (3 H, s), 2.41 (3 H, d, 4J =
0.65), 6.91–7.03 (2 H, m), 7.08–7.19 (1 H,
(CDCl3): 16.6 (q), 21.8 (q), 110.7 (d, 2J =
20.1), 113.9 (s, 2J = 20.8), 115.4 (d, 2J =
268 (100), 267
(11), 253 (27),
m), 7.23–7.34 (1 H, m), 7.38–7.53 (2 H, m), 24.6), 116.5 (d, 2J = 20.5), 125.3 (s, 3J = 3.0), 252 (17), 233
7.55 (1 H, m), 7.98–8.07 (1 H, m)
125.5 (d, 3J = 5.2), 127.0 (s, 8J = 8.9), 128.3 (22)
(d, 4J = 1.1), 130.0 (s, 3J = 8.6), 131.7 (s, 4J =
1.5), 134.0 (s, 3J = 8.9), 135.4 (d, 4J = 0.7),
138.3 (d, 4J = 2.6), 143.7 (d, 3J = 7.45), 160.8
(s, 1J = 245.6), 162.9 (s, 1J = 246.7)
3g
3h
63
oil
(CDCl3): 2.19 (3 H, s), 2.37 (3 H, d, 4J =
(CDCl3): 16.6 (q), 21.8 (q), 108.6 (d, 2J =
268 (100), 267
(8), 253 (24),
0.65), 7.18 (2 H, m), 7.22 (2 H, m), 7.31 (1 H, 21.7), 115.9 (s, 2J = 21.7), 116.3 (d, 2J =
m), 7.64 (2 H, m), 7.67 (1 H, m), 7.82 (1 H,
m)
24.6), 126.4 (d), 130.0 (s), 130.6 (d, 3J = 8.9), 252 (15), 251
131.3 (s, 3J = 7.9), 131.8 (d, 4J = 2.9), 132.7 (32), 233 (18)
(s, 3J = 7.9), 134.3 (s, 4J = 2.9), 137.8 (s, 4J =
4.9), 140.7 (d), 161.3 (s, 1J = 244.1), 162.9 (s,
1J = 245.1)
(CDCl3): 2.49 (3 H, d, 4J = 1.3), 2.72 (3 H, d, (CDCl3): 14.3 (q), 19.0 (q), 19.7 (q), 19.9 (q), 260 (100), 245
4J = 0.6), 2.74 (3 H, t, 4J = 0.6), 2.86 (3 H, d, 121.4 (d), 123.4 (d), 125.4 (d), 125.5 (d),
(24), 230 (14),
229 (16), 215
(12), 114 (11)
4J = 0.95), 7.39 (2 H, dt, 3J = 8.3, 4J = 1.9),
7.54 (2 H, m), 7.61 (1 H, dd, 3J = 8.3, 4J =
126.8 (d), 127.1 (d), 128.6 (s), 129.0 (s),
129.4 (s), 131.3 (s), 132.3 (s), 133.8 (s),
1.9), 7.85 (1 H, br s), 7.99 (1 H, d, 3J = 8.3), 136.7 (s), 138.1 (s)
8.13 (1 H, sext, 4J=5J=0.95)
Synthesis 1999, No. 9, 1651–1655 ISSN 0039-7881 © Thieme Stuttgart · New York

1654
R. Dupont, P. Cotelle
PAPER
Table 2 (continued)
Prod-
uct
mp (°C),
Solvent
1H NMR (200 MHz, TMS)
d, J (Hz)
13C NMR (50 MHz, TMS)
d
MS m/z
(%)
3i
125
162
oil
(CDCl3): 2.27 (3 H, d, 4J = 0.7), 2.46 (3 H, s), (CDCl3): 16.8 (q), 21.7 (q), 121.1 (d), 122.8 MALDI+ :
7.37–7.40 (3 H, m), 7.56 (1 H, ddd, 3J = 8.2, (d), 123.2 (d), 125.6 (d), 125.63 (d), 125.8
3J = 6.5, 4J = 1.7), 7.67 (1 H, dd, 3J = 8.2, 3J = (d), 126.12 (d), 126.15 (d), 126.3 (d), 126.4
332
7.0), 7.64–7.78 (2 H, m), 7.85 (1 H, d, 3J =
9.3), 8.00 (1 H, m), 8.02 (1 H, dd, 3J = 7.5,
(d), 126.8 (d), 127.3 (d), 128.3 (d), 128.4 (d),
129.2 (s), 129.7 (s), 130.3 (s), 131.7 (s),
4J = 1.6), 8.04 (1 H, dt, 3J = 8.4, 4J = 1.0), 8.11 132.1 (s), 133.4 (s), 133.7 (s), 135.6 (s),
(1 H, dd, 3J = 9.3, 4J = 0.7), 8.66 (1 H, quint, 138.6 (s), 139.2 (s)
4J = 0.7), 8.85 (1 H, m)
5i
(CDCl3): 2.19 (3 H, d, 4J = 0.9), 2.36 (3 H, s), (CDCl3) : 16.8 (q), 21.8 (q), 121.2 (d), 123.0 MALDI+ :
7.34–7.40 (3 H, m), 7.53 (1 H, ddd, 3J = 8.1, (d), 125.4(d), 125.6 (d), 125.9 (d), 126.2 (d), 412, 410
3J = 5.0, 4J = 3.1), 7.63 (1 H, dd, 3J = 8.3, 3J = 126.8 (d), 127.25 (d), 127.27 (d), 127.3 (d),
6.95), 7.70–7.77 (2 H, m), 7.98 (1 H, dd, 3J = 127.5 (d), 127.9 (d), 128.3 (d), 129.0 (s),
8.2, 4J = 1.5), 8.00 (1 H, dt, 3J = 8.2, 4J = 1.1), 129.2 (s), 129.7 (s), 130.1 (s), 131.3 (s),
8.41 (1 H, d, 5J = 0.7), 8.46 (1 H, m), 8.54
(1 H, quint, 4J = 0.9, 5J = 0.7), 8.79
(1 H, m)
131.9 (s), 132.8 (s), 133.7 (s), 136.3 (s),
138.8 (s), 139.3 (s)
2j
(CDCl3): 1.54 (3 H, s), 2.08 (3 H, s), 3.81
(2 H, s), 7.39–7.67 (8 H, m)
(CDCl3): 20.5 (q), 30.9 (q), 40.7 (t), 123.4 (d, 386 (100), 371
3J = 3.8), 123.9 (s, 1J = 272), 124.2 (s, 1J =
(37), 343 (22),
272), 124.6 (d, 3J = 3.8), 125.8 (d, 3J = 3.8), 243 (26), 227
126.2 (d, 3J = 3.8), 128.9 (d), 129.4 (d), 130.8 (27), 199 (32),
(s, 2J = 32.4), 131.4 (s, 2J = 32.4), 132.4 (d,
197 (19), 173
4J = 1.1), 132.9 (d, 4J = 1.1), 139.0 (s), 139.8 (59), 159 (67),
(s), 139.9 (s), 143.7 (s), 201.4 (s)
145 (16), 115
(16), 109 (18)
6n
53
(CDCl3): 2.44 (3 H, d, 4J = 1.3), 6.37 (1 H, m), (CDCl3): 14.0 (q), 103.3 (d), 109.7 (d), 112.5 148 (100), 147
6.77 (1 H, m), 7.03–7.06 (2 H, m) (d), 123.4 (d), 130.9 (s), 140.5 (s), 143.0 (s), (87), 119 (10),
155.9 (s)
91 (25), 74
(12), 65 (12)
6o
6p
3q
73
(CDCl3): 2.41 (3 H, d, 4J = 1.1), 6.28 (1 H, m), (CDCl3): 14.0 (q), 98.0 (d), 102.2 (d), 111.3 148 (70), 147
6.74 (1 H, dd, 3J = 8.1, 4J = 2.3), 6.94 (1 H, d, (d), 120.1 (d), 122.8 (s), 152.7 (s), 154.5 (s), (100), 91 (10),
4J = 2.3), 7.28 (1 H, d, 3J = 8.1)
155.5 (s)
74 (8), 65 (10)
45
(CDCl3): 2.42 (3 H, d, 4J = 1.1), 6.26 (1 H, m), (CDCl3): 14.1 (q), 102.6 (d), 105.4 (d), 110.9 148 (58), 147
6.71 (1 H, dd, 3J = 8.7, 4J = 2.6), 6.90 (1 H, d, (d), 111.4 (d), 130.1 (s), 149.8 (s), 151.3 (s), (100), 91 (8),
4J = 2.6), 7.24 (1 H, d, 3J = 8.7)
156.6 (s)
74 (8), 65 (7)
255, Acetone
(DMSO-d6): 2.01 (3 H, br s), 2.16 (3 H, s),
(DMSO-d6): 16.5 (q), 21.4 (q), 106.9 (d),
296 (100)
6.36 (1 H, dd, 3J = 7.9, 4J = 1.9), 6.48 (1 H, d, 109.6 (d), 115.6 (d), 116.7 (d), 120.1 (d),
4J = 1.9), 6.79 (1 H, d, 3J = 7.9), 7.01 (1 H, s), 123.5 (s), 126.3 (d), 127.9 (s), 128.6 (s),
7.16 (1 H, s), 7.27 ( 1H, s)
130.8 (s), 132.6 (s), 137.2 (s), 143.7 (s),
144.9 (s), 146.1 (s), 146.2 (s)
a Satisfactory microanalyses obtained for all new compounds: C ± 0.38; H ± 0.18; O ± 0.47
b
3b solidified after chromatographic purification
formation of 2-methylbenzo[b]furans and (iii) activated TLC analyses were performed on a 3 × 10 cm plastic sheet
phenanthrenes may react with boron tribromide or hydro- precoated with silica gel 60F254 (Merck) (Solvent sys-
gen bromide (formed during the reaction) to give bromi- tem: EtOAc/hexane 1/4). SiO2, 200-400 mesh (Merck)
nated phenanthrene. In addition, another side reaction, was used for column chromatography. Mps were deter-
observed with phenylethanal but not with arylacetone, mined on a Reichert Thermopan apparatus, equipped with
may occur, i.e., the direct bromination of the carbonyl a microscope and are uncorrected. NMR spectra were ob-
function of phenylethanal leading to 1,1-dibromo-2-phe- tained on a AC 200 Bruker spectrometer in the appropri-
nylethane. Further studies are presently undertaken in or- ate solvent with TMS as internal reference. Mass spectra
der to promote cross-condensation in a one-pot procedure: were recorded on a Ribermag R 10-10 spectrometer (Elec-
(i) from arylacetones with very different reactivities (i.e., tron Impact, 60 eV) or on a Finnigan MAT vision 2000
activated and inactivated arylacetones), (ii) from arylace- spectrometer (MALDI). Elemental analysis were per-
tones and arylethanals or in a two-steps procedure by syn- formed by CNRS laboratories (Vernaison) and were with-
thesizing enolates prior to the BBr3 treatment.
in 0.4% of the theorical value.
Synthesis 1999, No. 9, 1651–1655 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Reaction of Arylacetones with Boron Tribromide
1655
Boron tribromide and arylacetones 1a–e, 1g, 1j and 1q were pur-
chased from Aldrich-Chimie (St Quentin-Fallavier, France). 1h was
obtained from Trans World Chemicals Inc. (Rockville, USA). Ary-
lacetones 1f, 1i and 1n–p were prepared in three steps from the con-
venient benzaldehydes according to known procedures.9-11
Arylacetones 1k–m were prepared from the convenient anilines ac-
cording to S. Raucher and G. A. Koolpe.12
d) Karady, S.; Amato, J. S.; Reamer, R. A.; Weinstock, L. M.
Tetrahedron Lett. 1996, 37, 8277.
e) Jamie, J. F.; Rickards, R. W. J. Chem. Soc. Perkin Trans. 1
1996, 2603.
f) De Konig, C. B.; Michael, J. P.; Rousseau, A. L.
Tetrahedron Lett. 1997, 38, 893.
g) Katritzky, A. R.; Zhang, G.; Xie, L. J. Org. Chem. 1997, 62,
721.
(3) Smyth, M. S.; Stefanova, I.; Horak, I. D.; Burke, T. R. J. Med.
Reaction of Arylacetones with Boron Tribromide: General Pro-
cedure
Chem. 1993, 36, 3015.
(4) Cotelle, P.; Catteau, J. P. Tetrahedron Lett. 1997, 38, 2969.
(5) Dupont, R.; Cotelle, P. Tetrahedron Lett. 1998, 39, 8457.
(6) Cherkaoui, O.; Nebois, P.; Fillion, H.; Domard, M.; Fenet, B.
Tetrahedron 1996, 52, 9499.
BBr3 (1 M in CH2Cl2, 10 mL, 10 mmol for 1a, 1e–i and 1j–m, 15
mL, 15 mmol for 1b–d or 20 mL, 20 mmol for 1n–q) was added
dropwise to a solution of arylacetones (5 mmol) in CH2Cl2 (20 mL)
at r.t.. The mixture was stirred for 1h, then H2O (40 mL) was added
dropwise. The solid was filtered off, dried and crystallized from ac-
etone (3d and 3q) or CH2Cl2 (3c) or purified by column chromatog-
raphy. In the other cases, no solid was obtained and the aqueous
layer was extracted with CH2Cl2 (2 x 20 mL). The organic layer was
dried (MgSO4), the solvent evaporated and the residue was purified
by column chromatography.
(7) Baxter, G. J.; Brown, R. F. C.; Mac Mullen, G. L. Aust. J.
Chem. 1974, 27, 2605.
(8) Royer, R.; Risse, S.; Demerseman, P.; Albert, O.; Nicoine, F.
Eur. J. Med. Chem. 1979, 14, 223.
(9) Miseka, Y.; Mizutani, T.; Sekido, M.; Uyeo, S. J. Chem. Soc.
1968, 2954.
(10) Sinhababu, A. K.; Borchardt, R. T. Tetrahedron Lett. 1983,
24, 227.
(11) Olah, G. A.; Arvanaghi, M.; Vankar, Y. D.; Prakash, G. K. S.
Synthesis 1980, 662.
Acknowledgement
(12) Raucher, S.; Koolpe, G. A. J. Org. Chem. 1983, 48, 2066.
(13) Cantrell, T. S.; John, B.; Johnson, L.; Allen, A. C. Forensic.
Sci. Int. 1988, 39, 39.
(14) Kurz, M. E.; Baru, V.; Nguyen, P. N. J. Org. Chem. 1984, 49,
1603.
This work was supported by grants from the Centre National de la
Recherche Scientifique (CNRS) and the Région Nord-Pas-de-Ca-
lais.
(15) Satoh, T.; Itoh, N.; Gengyo, K.; Takada, S.; Asakawa, N.;
Yamani, Y.; Yamakawa, K. Tetrahedron 1994, 50, 11839.
(16) Shtacher, G.; Dayagi, S. J. Med. Chem. 1972, 15, 1174.
(17) Augustine, R. L.; Gustavsen, A. J.; Wanat, S. F.; Pattison, I.
C.; Koughton, K. S.; Koletar, G. J. Org. Chem. 1973, 38,
3004.
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Synthesis 1999, No. 9, 1651–1655 ISSN 0039-7881 © Thieme Stuttgart · New York