Synthesis of functionalized salicylates by formal [3+3] cyclocondensation of 1,3-bis(silyloxy)buta-1,3-dienes with 3-alkoxy-2-en-1-ones

Article abstract of DOI:10.1055/s-0029-1216814

The formal [3+3] cyclization of 1,3-bis(silyloxy)buta-1,3-dienes with 1-aryl-3-ethoxyprop-2-en-1-ones, available by Heck reaction of benzoyl chlorides with ethyl vinyl ether, afforded a variety of 6-arylsalicylates. The reaction of the products with conce

Full text of DOI:10.1055/s-0029-1216814

2236
PAPER
Synthesis of Functionalized Salicylates by Formal [3+3] Cyclocondensation of
1,3-Bis(silyloxy)buta-1,3-dienes with 3-Alkoxy-2-en-1-ones
S
ynthesis of Funct
e
ionalized S
r
alicylate
s
s
on Mroß,a Simone Ladzik,a Helmut Reinke,a Anke Spannenberg,b Christine Fischer,b Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
E-mail: peter.langer@uni-rostock.de
b
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Received 6 September 2008; revised 26 March 2009
the synthesis of a variety of functionalized arenes. Recent-
ly, we have reported the synthesis of aryl-substituted sali-
cylates by application of a ‘Heck cross-coupling/[3+3]
cyclization’ strategy.13 Herein, we report full details of
Abstract: The formal [3+3] cyclization of 1,3-bis(silyloxy)buta-
1,3-dienes with 1-aryl-3-ethoxyprop-2-en-1-ones, available by
Heck reaction of benzoyl chlorides with ethyl vinyl ether, afforded
a variety of 6-arylsalicylates. The reaction of the products with con-
centrated sulfuric acid resulted in the formation of fluorenones. 6- this study. With regard to our preliminary communica-
Alkylsalicylates were prepared by cyclization of 1,3-bis(silyl-
oxy)buta-1,3-dienes with aliphatic enones.
tion, the scope was extended to alkyl-substituted deriva-
tives. In addition, the method was applied to the synthesis
Key words: arenes, cyclizations, palladium, regioselectivity, silyl
enol ethers
of novel functionalized fluorenones. It is worth noting that
the sterically encumbered and functionalized arenes pre-
pared are not readily available by other methods.
1-Aryl-3-ethoxyprop-2-en-1-ones 3a–f were prepared,
following a known procedure,14 by Heck reaction of ben-
zoyl chlorides 1a–f with ethyl vinyl ether (2) (Scheme 1).
The best yields of enones 3 were obtained for 3a, 3b, and
3f. While 3f, containing three methoxy groups located at
the phenyl group, could be isolated in good yield, lower
yields were observed for 3d and 3e each containing only
one methoxy group. 1,3-Bis(trimethylsilyloxy)buta-1,3-
dienes 4a–k are available from the corresponding 1,3-di-
carbonyl compounds in two steps.10 The TiCl4-mediated
cyclization of 3a–f with 1,3-bis(trimethylsilyloxy)buta-
1,3-dienes 4a–k afforded the 6-arylsalicylates 5a–t
(Scheme 1, Table 1). All cyclizations proceeded with ex-
cellent regioselectivity in favor of the isomers containing
the aryl group located ortho to the ester group. All prod-
ucts were isomerically pure (ratio >98:2). The regioiso-
mers, containing the aryl group located para to the ester
6-Alkyl- and 6-arylsalicylates are of considerable phar-
macological importance. Aryl-substituted salicylates can
be regarded as functionalized biphenyl derivatives and
represent important substructures of pharmacologically
relevant natural and non-natural molecules. Examples in-
clude cytotoxic and hepatoprotective glycoside esters
(e.g., amaroswerin),1 cancerostatic benzo[1,2-c]phenan-
thridin-14-ones (e.g., sanguinarinone and oxysangui-
narine),2 dibenzo[b,d]pyran-6-ones (e.g., the antitumor-
active graphislactones),3 simple biaryls,4 complex macro-
cycles (e.g., sanguine),5 dibenzoorthoquinones (e.g., mu-
rayaquinone),6
9,10-dihydrophenanthrenes
(e.g.,
juncunone),7 and the cynandiones (exhibiting a consider-
able in vitro activity against hepatocytes, human bladder
carcinoma T-24 cells, epidermoid carcinoma KB cells,
and human hepatoma PLC/PRF/5 cells).8
Palladium(0)-catalyzed cross-coupling reactions consti- group, could not be isolated. The best yields of products 5
tute the most widely used synthetic approach to biphenyl were generally obtained when the reaction was carried out
derivatives.9 In general, these methods are broadly appli-
cable. However, the synthesis of sterically encumbered
O
products can be difficult or not possible at all. In addition,
the synthesis of the required starting materials, function-
alized aryl halides or phenols, can be a difficult and te-
dious task, due to the low regioselectivity of electrophilic
aromatic substitution reactions (e.g., brominations) or due
to the low reactivity of electron-poor arenes. An alterna-
tive strategy for the synthesis of biphenyls relies on the as-
sembly of the benzene moiety by cyclization reactions.
Chan et al. were the first to report10 the formal [3+3]
R3
R2
Pd(OAc)2
(1 mol%)
Et3N
Cl
O
R3
R2
+
EtO
R1
24–48 h
80 °C
EtO
R1
3a–f
1a–f
2
Me3SiO
OSiMe3
R5
OH
O
R4
R4
cyclization11
of
1,3-bis(trimethylsilyloxy)buta-1,3-
R5
4a–k
dienes12 with 3-trimethylsilyloxy-2-en-1-ones. In recent
years, we have reported the application of this method to
R3
R2
TiCl4, CH2Cl2
–78 to 20 °C
12 h
5a–t
SYNTHESIS 2009, No. 13, pp 2236–2248
x
x.
x
x
.
2
0
0
9
R1
Advanced online publication: 25.05.2009
DOI: 10.1055/s-0029-1216814; Art ID: T15708SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Synthesis of 6-arylsalicylates 5a–t

PAPER
Synthesis of Functionalized Salicylates
2237
Table 1 Synthesis of 6-Arylsalicylates 5a–t
3
4
5
R1
R2
R3
R4
R5
3
5
Yield (%)a Yield (%)a
a
a
a
a
a
a
a
b
b
b
b
c
d
d
d
e
e
f
a
b
c
d
e
f
a
b
c
d
e
f
H
H
H
H
OMe
O(CH2)2OMe
OEt
49
–
36
30
43
56
70
32
20
35
25
33
24
30
48
48
86
20
30
31
37
12
H
H
H
H
H
H
H
Et
–
H
H
H
n-Pr
n-C8H17
(CH2)3Ph
OMe
H
OMe
OMe
OMe
OMe
OMe
OEt
–
H
H
H
–
H
H
H
–
g
a
c
f
g
h
i
H
H
H
–
H
Cl
H
51
–
H
Cl
H
Et
j
H
Cl
H
(CH2)3Ph
OMe
H
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
Oi-Bu
OMe
Et
–
g
a
a
h
d
a
i
k
l
H
Cl
H
–
H
NO2
OMe
OMe
OMe
H
H
22
32
–
m
n
o
p
q
r
s
H
H
H
H
H
Me
H
H
n-Pr
H
–
OMe
OMe
OMe
OMe
OMe
H
30
–
H
H
n-C6H13
H
j
OMe
OMe
OMe
OMe
OMe
OMe
54
–
f
f
(CH2)3Ph
Me
f
k
t
–
a Yields of isolated products.
in a highly concentrated solution using stoichiometric 5m–o. The yields of the products derived from dienes 4c–
amounts of the starting materials.
e,i, containing an alkyl group attached to carbon C-4 of
the diene moiety, are generally higher than the yields of
those products derived from unsubstituted dienes. The
low yield of 5t can be explained by the generally lower re-
activity of 1,3-diketone-derived compared to b-keto ester-
derived 1,3-bis(trimethylsilyloxy)buta-1,3-dienes. The
Heck reaction of ortho-substituted benzoyl chlorides
failed to give the corresponding enones. All other at-
tempts to prepare these compounds also failed (e.g., the
reaction of ortho-substituted acetophenone derivatives
with triethyl orthoformate). Therefore, the reaction of
ortho-substituted 1-aryl-3-ethoxyprop-2-en-1-ones with
1,3-bis(silyloxy)buta-1,3-dienes could not be studied.
The regioselective formation of 5a can be explained by
the reaction of 3a with TiCl4 to give first the allylic cation
A. The attack of the terminal carbon atom of 4a onto A re-
sults in the formation of intermediate B. The elimination
of (methoxy)trimethylsilane (intermediate C) and subse-
quent cyclization give the intermediate D. The elimination
of titanium hydroxide and aromatization result in the for-
mation of product 5a (Scheme 2).
Regarding the [3+3] cyclocondensations, the best yields
were obtained for products 5n and 5o derived from enone
3d (containing one methoxy group located at the para-po-
sition of the phenyl group). Interestingly, the yields of
products 5m–o, derived from 3d, are generally higher
than those of the products derived from 3e (containing one
methoxy group located at the meta-position) or derived
The structures of all products were established by spectro-
scopic methods. The structure of 5i was independently
confirmed by X-ray crystal structure analysis (Figure 1).15
from 3f (containing three methoxy groups). The yields of The hydroxyl group of the 6-arylsalicylates can be func-
products 5h–k and 5l, containing an electron-withdrawing tionalized by palladium-catalyzed cross-coupling reac-
chloro or nitro group located at the para-position of the tions.16 Biaryl derivative 5a was transformed into its
phenyl group, were generally lower than those of products triflate 6 (Scheme 3). The Suzuki reaction of 6 with phe-
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

2238
G. Mroß et al.
PAPER
Me3SiO
OSiMe3
O
OH
TiCl4
CH2Cl2
OMe
OMe
4a
EtO
O
–78 to 20 °C
18 h
Ph
+
Ph
5a
3a
TiCl4
H2O
O
O
–
TiCl4
EtO
O
OMe
OTiCl3
Ph
+
Ph
A
D
Figure 2 X-ray crystal structure of 7
1a
Me3SiCl
Me3SiCl
d. It is noteworthy that these reactions represent what are,
to the best of our knowledge, the first [3+3] cyclizations
of bromine-containing substrates. The transformations are
of synthetic utility, since the bromide group can be further
functionalized by palladium(0)-catalyzed cross-coupling
reactions and other transformations. Generally, highly
substituted brominated arenes are not readily available by
electrophilic substitutions, due to the formation of regio-
isomers. The structure of 9a was independently confirmed
by X-ray crystal structure analysis.13
O
O
Me3SiO
OMe
TiCl3
Me3SiO
OMe
TiCl4
Me3SiCl
O
O
Ph
Ph
Me3SiOEt
EtO
B
C
Scheme 2 Regioselectivity of the cyclization of 3a with 4a
The structures of salicylates 5a,d,e,k, and 9b were inde-
pendently confirmed as follows: Treatment of these com-
pounds with concentrated sulfuric acid, following
conditions earlier reported by us,16 resulted in the forma-
tion of the novel fluorenones 10a–e in excellent yields
(Scheme 5, Table 3). This result indicates that the phenyl
O
O
1) Br2, CH2Cl2
1 h, 0 °C
EtO
EtO
2) Et3N, 15 min
Br
8a, b
R1
R1
3a, e
Me3SiO
R2
OSiMe3
R3
OH
O
Figure 1 X-ray crystal structure of 5i
R2
R3
4
OR
O
Ph
O
TiCl4, CH2Cl2
–78 to 20 °C, 12 h
Br
OMe
OMe
ii
R1
9a–d
Ph
Ph
5a R = H
R = Tf
Scheme 4 Synthesis of 6-aryl-5-bromosalicylates 9a–d
Table 2 Synthesis of 6-Aryl-5-bromosalicylates 9a–d
7 (50%)
i
6
Scheme 3 Synthesis of 7: Reagents and conditions: i) Tf2O, pyrid-
ine, –78 to –10 °C; ii) PhB(OH)2, K3PO4, Pd(PPh3)4, 1,4-dioxane, 12
h, reflux
3
8
4
9
R1
R2
R3
8 Yield 9 Yield
(%)a
61
–
(%)a
nylboronic acid afforded product 7. The structure of 7 was
independently confirmed by X-ray crystal structure anal-
ysis (Figure 2).15
a
a
e
e
a
a
b
b
a
h
h
l
a
b
c
H
H
OMe
OMe
OMe
OEt
50
H
Me
Me
H
52
The bromination of 3a and 3e afforded 8a and 8b, respec-
tively (Scheme 4, Table 2). The TiCl4-mediated cycliza-
tion of 8a,b with 1,3-bis(trimethylsilyloxy)buta-1,3-
MeO
36
–
48
d
MeO
22
dienes 4a,h,l afforded the 6-aryl-5-bromosalicylates 9a– a Yields of isolated products.
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Salicylates
Table 4 Synthesis of phenols 13a–n
2239
OH
O
OH
O
R2
R2
R1
R2
R3
13
rsb
OMe
11,12
4
13
i
Yield
(%)a
R1
R3
R1
R3
11a
11a
11a
11a
11a
11a
11b
11c
12a
12a
12a
12a
12b
12b
h
g
m
b
n
i
a
b
c
d
e
f
Me
Me
Me
Me
Me
Me
Et
Me
OMe
H
OMe
OMe
Me
40
38
33
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
4:1
5a,d,e,k, 9b
10a–e
Scheme 5 Synthesis of fluorenones 10a–e: Reagents and condi-
tions: i) H2SO4, 1 h, 0 °C
H
O(CH2)2OMe 24
Table 3 Synthesis of 10a–e
Cl
OEt
15
55
30
18
56
46
72
34
32
28
Starting
material
10
R1
R2
R3
10 Yield
(%)a
n-C6H13 OMe
5a
5e
5d
5k
9b
a
b
c
H
H
H
Cl
H
H
H
H
H
H
Br
81
84
96
96
82
h
h
l
g
h
i
Me
OMe
OMe
OEt
Me
n-C8H17
n-Pr
OMe
Me
n-Pr Me
>98:2
6:1
Et
H
d
e
m
n
k
l
j
Et
H
4:1
k
l
Et
H
Ph
4:1
a Yields of isolated products.
Et
Me
H
Et
4:1
m
n
n-Pr
OEt
OMe
10:1
8:1
group of the starting material is located ortho to the ester
group.
g
n-Pr OMe
The TiCl4-mediated cyclization of 1,3-bis(silyloxy)buta-
1,3-dienes 4b,g,h,i,m,n with 4-methoxybut-3-en-2-one
(11a) afforded the 6-methylsalicylates 13a–f (Scheme 6,
Table 4). Chan and Brownbridge previously reported the
cyclization of 4a with 11a.10a All products were formed
with excellent regioselectivity in favor of the isomer con-
taining the methyl group (R1) located ortho to the ester
group.
a Yields of isolated products.
b Regioselectivity in favor of the isomer containing the alkyl group R1
located ortho to the COR3 group.
low yield, from the reaction of 4h with 6-methoxyhex-5-
en-4-one (11c).
The TiCl4-mediated cyclization of 1,3-bis(silyloxy)buta-
1,3-dienes 4g,k–n with ketoacetals 12a and 12b afforded
products 13i–n as mixtures of regioisomers. The ratios
vary from 4:1 to 10:1. The major isomers contain the ethyl
or propyl group located ortho to the ester or acyl group.
The yields of the products derived from 12a are generally
higher than the yields of those products derived from 12b.
OH
O
R2
R3
Me3SiO
OSiMe3
R3
R2
R1
O
TiCl4
CH2Cl2
+
OH
4
In conclusion, we have reported a convenient and regiose-
lective synthesis of 6-alkyl- and 6-arylsalicylates by for-
mal [3+3] cyclizations of 1,3-bis(silyloxy)buta-1,3-dienes
with 3-alkoxyprop-2-en-1-ones.
+
OMe
O
OMe
O
–78 to 20°C
R2
or
R3
R1
MeO
R1
12a,b
11a–c
R1
13a–n
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere. For 1H and 13C NMR spectra
the deuterated solvents indicated were used. Mass spectrometric
data were obtained by electron ionization (EI, 70 eV), chemical ion-
ization (CI, isobutane), or electrospray ionization (ESI). For prepar-
ative scale chromatography silica gel 60 (0.063–0.200 mm, 70–
230 mesh) was used.
Scheme 6 Synthesis of phenols 13a–n
The yields of products 13a and 13f, derived from dienes
containing an alkyl group attached to carbon C-4 of the di-
ene, were higher than those of the products derived from
unsubstituted dienes. The cyclization of 4h with 5-meth-
oxypent-4-en-3-one (11b) afforded the 6-ethylsalicylate
13g. The yield of 13g was lower than the yield of product
13a derived from 11a. In addition, the product was isolat-
ed as a 4:1 mixture of regioisomers (the major isomer con-
tains the ethyl group located ortho to the ester group).
Product 13h was isolated as a pure regioisomer, albeit in
Heck Reaction of Ethyl Vinyl Ether with Acid Chlorides;
3-Ethoxy-1-phenylpropenone (3a) Typical Procedure14
To a mixture of ethyl vinyl ether (2.90 g, 40.0 mmol) and Et3N (1.20
g, 12.0 mmol) in a pressure tube was added Pd(OAc)2 (20 mg, 0.1
mmol) under argon. The mixture was stirred until a clear yellow so-
lution was formed. To the mixture was added benzoyl chloride
(1.20 g, 10.0 mmol) and stirred at 80 °C for 24 h. The mixture was
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

2240
G. Mroß et al.
PAPER
poured into Et2O (50 mL) and the solid (Et3N·HCl) was filtered off.
The filtrate was concentrated under reduced pressure and the resi-
due was purified by chromatography (silica gel, heptanes–
EtOAc, 10:1 → 5:1) to give 3a as a slightly yellow oil (3.80 g,
55%).
(w), 1288 (s), 1240 (s), 1193 (m), 1166 (s), 1150 (w), 1110 (w),
1101 (m), 1063 (w), 1017 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.61 (t, 3J = 7.1 Hz, 3 H,
OCH2CH3), 1.13 (t, 3J = 7.6 Hz, 3 H, CH2CH3), 2.60 (q, 3J = 7.6 Hz,
3
2 H, CH2CH3), 3.84 (q, J = 7.1 Hz, 2 H, OCH2CH3), 6.61 (d,
3J = 7.6 Hz, 1 Harom), 7.06–7.20 (m, 6 Harom), 10.86 (s, 1 H, OH).
Biphenyls 5a–t; 3-Hydroxybiphenyl-2-carboxylic Acid Methyl
Ester (5a); Typical Procedure
13C NMR (250 MHz, CDCl3): d = 12.9 (OCH2CH3), 13.6
(CH2CH3), 22.9 (CH2CH3), 60.9 (OCH2CH3), 111.6 (Carom), 121.7,
126.4, 127.5, 128.2 (CHarom), 131.4 (Carom), 132.7 (CHarom), 142.3,
143.3, 159.3 (Carom), 171.4 (C=O).
MS (EI, 70 eV): m/z (%) = 270 (M+, 57), 225 (16), 224 (76), 223
(20), 209 (42), 207 (18), 206 (100), 181 (24), 178 (16), 165 (18),
153 (209, 152 (40).
To a CH2Cl2 solution (1 mL) of 3-ethoxy-1-phenylpropenone (3a;
176 mg, 1.0 mmol) and of 4a (260 mg, 1.0 mmol) was added a
CH2Cl2 solution (5 mL) of TiCl4 (0.12 mL, 1.0 mmol) at –78 °C.
The temperature of the solution was allowed to warm to 20 °C with-
in 14 h. To the mixture was added CH2Cl2 (10 mL) and 10% aq HCl
(10 mL). The organic and the aqueous layers were separated and the
latter was extracted with CH2Cl2 (3 × 20 mL). The combined organ-
ic layers were dried (Na2SO4), filtered, and the filtrate was concen-
trated in vacuo. The residue was purified by chromatography
(heptanes–EtOAc, 10:1) to give 5a as a slightly yellow oil (0.081 g,
36%).
HRMS (EI): m/z calcd for C17H18O3 (M+): 270.1250; found:
270.1253.
3-Hydroxy-4-propylbiphenyl-2-carboxylic Acid Methyl Ester
(5d)
IR (neat): 3059 (w), 3028 (w), 2952 (w), 2851 (w), 1735 (w), 1667
(s), 1601 (m), 1571 (m), 1501 (w), 1439 (s), 1343 (m), 1270 (m),
1220 (s), 1172 (m), 1124 (m), 1097 (m), 1065 cm–1 (w).
Starting from 3a (0.352 g, 2.0 mmol) and 1-methoxy-1,3-bis(tri-
methylsilyloxy)hepta-1,3-diene (4d; 0.906 g, 3.0 mmol) in CH2Cl2
(5 mL), 5d was isolated as a yellow oil (0.300 g, 56%).
1H NMR (300 MHz, CDCl3): d = 3.35 (s, 3 H, OCH3), 6.68 (d,
3J = 7.5 Hz, 1 Harom), 6.87 (d, 3J = 8.3 Hz, 1 Harom), 7.08–7.30 (m, 6
Harom), 10.49 (s, 1 H, OH).
IR (neat): 3057 (w), 3026 (w), 2955 (m), 2931 (m), 2870 (w), 1661
(s), 1610 (m), 1600 (m), 1567 (m), 1436 (s), 1413 (s), 1343 (m),
1268 (s), 1236 (s), 1195 (s), 1144 (s), 1105 (m), 1073 cm–1 (w).
13C NMR (250 MHz, CDCl3): d = 52.0 (OCH3), 112.5 (Carom),
117.0, 123.0, 127.2, 128.0, 128.5, 134.0 (CHarom), 143.0, 145.2,
161.7 (Carom), 171.7 (C=O).
1H NMR (300 MHz, CDCl3): d = 0.99 (t, 3J = 7.3 Hz, 3 H,
3
CH2CH2CH3), 1.68 (sext, J = 7.6 Hz, 2 H, CH2CH2CH3), 2.67 (t,
3J = 7.3 Hz, 2 H, CH2CH2CH3), 3.47 (s, 3 H, OCH3), 6.73 (d,
3J = 7.6 Hz, 1 Harom), 7.19–7.36 (m, 6 Harom), 10.79 (s, 1 H, OH).
MS (EI, 70 eV): m/z (%) = 228 (M+, 36), 196 (100), 168 (53), 139
13C NMR (250 MHz, CDCl3): d = 14.0 (CH3), 22.5, 31.9 (CH2),
51.6 (OCH3), 111.5 (Carom), 121.8, 126.5, 127.5, 128.1 (CHarom),
129.9 (Carom), 133.8 (CHarom), 142.2, 142.9, 159.2 (Carom), 171.8
(C=O).
(33).
HRMS (EI): m/z calcd for C14H12O3 (M+): 228.0781; found:
228.0786.
MS (EI, 70 eV): m/z (%) = 270 (M+, 71), 238 (69), 237 (23), 221
(59), 210 (83), 209 (100), 196 (22), 181 (21), 165 (19), 153 (25),
152 (77), 151 (17).
3-Hydroxybiphenyl-2-carboxylic Acid Methoxyethyl Ester (5b)
Starting from 3a (0.352 g, 2.0 mmol) and 1-(2-methoxyethoxy)-
1,3-bis(trimethylsilyloxy)buta-1,3-diene (4b; 0.912 g, 3.0 mmol) in
CH2Cl2 (5 mL), 5b was isolated as a yellow oil (0.082 g, 30%).
HRMS (EI): m/z calcd for C17H18O3 (M+): 270.1250; found:
IR (neat): 3057 (w), 3026 (w), 2982 (w), 2927 (w), 2881 (w), 2840
(w), 2819 (w), 1732 (w), 1659 (s), 1598 (m), 1570 (m), 1500 (w),
1449 (m), 1437 (m), 1406 (w), 1375 (m), 1312 (m), 1268 (s), 1215
(s), 1172 (s), 1120 (s), 1094 (s), 1063 (m), 1024 cm–1 (m).
270.1254.
3-Hydroxy-4-octylbiphenyl-2-carboxylic Acid Methyl Ester
(5e)
Starting from 3a (0.328 g, 2.0 mmol) and 1-methoxy-1,3-bis(tri-
methylsilyloxy)dodeca-1,3-diene (4e; 1.117 g, 3.0 mmol) in
CH2Cl2 (5 mL), 5e was isolated as a yellow oil (0.476 g, 70%).
3
1H NMR (300 MHz, CDCl3): d = 2.95 (t, J = 4.8 Hz, 2 H, CH2),
3.06 (s, 3 H, OCH3), 4.02 (t, 3J = 4.8 Hz, 2 H, CH2), 6.71 (d, 3J = 7.4
Hz, 1 Harom), 6.91 (d, 3J = 8.3 Hz, 1 Harom), 7.15–7.35 (m, 6 Harom),
10.51 (s, 1 H, OH).
IR (neat): 3026 (w), 2952 (m), 2922 (s), 2853 (s), 1751 (w), 1714
(w), 1662 (s), 1623 (m), 1601 (w), 1569 (w), 1437 (s), 1414 (m),
1376 (m), 1342 (m), 1312 (m), 1268 (m), 1233 (s), 1196 (m), 1145
(s), 1109 (w), 1072 cm–1 (w).
13C NMR (250 MHz, CDCl3): d = 58.6 (OCH3), 63.8, 69.1 (CH2),
112.1 (Carom), 116.6, 122.5, 126.6, 127.5, 128.2, 133.6 (CHarom),
142.9, 144.9, 161.3 (Carom), 170.6 (C=O).
1H NMR (300 MHz, CDCl3): d = 0.87 [t, 3J = 6.7 Hz, 3 H,
CH2(CH2)6CH3], 1.25–1.67 [m, 12 H, CH2(CH2)6CH3], 2.68 [t,
3J = 7.6 Hz, 2 H, CH2(CH2)6CH3], 3.73 (s, 3 H, OCH3), 6.73 (d,
3J = 7.6 Hz, 1 Harom), 7.19–7.38 (m, 6 Harom), 10.78 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 14.0 (CH3), 22.6, 27.2, 29.2,
29.3, 29.6, 31.2, 31.8 (CH2), 51.6 (OCH3), 111.5 (Carom), 121.8,
126.5, 127.5, 128.1 (CHarom), 130.2 (Carom), 133.7 (CHarom), 142.9,
159.2, 171.8 (Carom), 206.4 (C=O).
MS (EI, 70 eV): m/z (%) = 272 (M+, 27), 197 (25), 196 (100), 168
(33), 139 (17).
HRMS (EI): m/z calcd for C16H16O4 (M+): 272.1043; found:
272.1040.
4-Ethyl-3-hydroxybiphenyl-2-carboxylic Acid Ethyl Ester (5c)
Starting from 3a (0.176 g, 1.0 mmol) and 1-ethoxy-1,3-bis(trimeth-
ylsilyloxy)hexa-1,3-diene (4c; 0.302 g, 1.0 mmol) in CH2Cl2 (5
mL), 5c was isolated as a colorless solid (0.109 g, 43%); mp 49–
51 °C.
MS (EI, 70 eV): m/z (%) = 340 (M+, 39), 210 (100), 209 (71), 180
(15), 153 (15), 152 (38).
HRMS (ESI): m/z calcd for C22H28O3 (M + H)+: 341.2111; found:
341.2109.
IR (neat): 3049 (w), 3022 (w), 2991 (w), 2963 (w), 2931 (w), 2873
(w), 1646 (s), 1615 (w), 1601 (w), 1567 (w), 1498 (w), 1470 (w),
1456(w), 1440 (w), 1417 (m), 1398 (m), 1372 (s), 1340 (m), 1303
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Salicylates
2241
3-Hydroxy-4-(3-phenylpropyl)biphenyl-2-carboxylic Acid
Methyl Ester (5f)
2H, CH2CH3), 4.01 (q, 3J = 7.1 Hz, 2 H, OCH2CH3), 6.68 (d,
3J = 7.6 Hz, 1 Harom), 7.13–7.41 (m, 5 Harom), 11.08 (s, 1 H, OH).
Starting from 3a (0.176 g, 1.0 mmol) and 7-methoxy-5,7-bis(tri-
methylsilyloxy)hepta-4,6-dienylbenzene (4f; 0.378 g, 1.0 mmol) in
CH2Cl2 (5 mL), 5f was isolated as a yellow oil (0.112 g, 32%).
13C NMR (250 MHz, CDCl3): d = 13.0 (OCH2CH3), 13.6
(CH2CH3), 22.9 (CH2CH3), 61.1 (OCH2CH3), 111.2 (Carom), 121.6,
127.6 (CHarom), 128.2 (C, Ar), 129.5 (CHarom), 131.9 (Carom), 132.8
(CHarom), 140.9, 141.8, 159.6 (Carom), 171.1 (C=O).
MS (EI, 70 eV): m/z (%) = 306 (M+, 37Cl, 24), 304 (M+, 35Cl, 69),
259 (49), 258 (43), 257 (100), 230 (18), 223 (79), 195 (21), 165
(33), 152 (38).
IR (neat): 3083 (w), 3059 (w), 3026 (m), 2949 (m), 2858 (w), 1663
(s), 1601 (m), 1568 (w), 1496 (m), 1437 (s), 1416 (s), 1345 (s), 1270
(s), 1240 (s), 1197 (s), 1151 (s), 1101 (w), 1075 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 1.87 (m, 2 H, CH2), 2.60 (m, 4 H,
CH2), 3.34 (s, 3 H, OCH3), 6.61 (d, 3J = 7.6 Hz, 1 Harom), 7.02–7.25
(m, 11 Harom), 10.69 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 29.6, 30.8, 35.7 (CH2), 51.6
(OCH3),111.6 (Carom), 121.8, 125.6, 126.6, 127.5, 128.1, 128.2,
128.4 (CHarom), 129.6 (Carom), 133.7 (CHarom), 142.3, 142.4, 142.9,
159.3 (Carom), 171.8 (C=O).
HRMS (EI): m/z calcd for C17H17ClO3 (M+): 304.0860; found:
304.0864.
4¢-Chloro-3-hydroxy-4-(3-phenylpropyl)biphenyl-2-carboxylic
Acid Methyl Ester (5j)
Starting from 3b (0.210 g, 1.0 mmol) and 4f (0.378 g, 1.0 mmol) in
CH2Cl2 (5 mL), 5j was isolated as a yellow solid (0.127 g, 33%);
mp 65–67 °C.
MS (EI, 70 eV): m/z (%) = 346 (M+, 29), 211 (15), 210 (100), 209
(18).
IR (neat): 3078 (w), 3057 (w), 3024 (w), 2939 (w), 2917 (w), 2855
(w), 1656 (s), 1612 (w), 1600 (w), 1576 (w), 1493 (m), 1436 (m),
1421 (s), 1396 (w), 1348 (s), 1299 (w), 1279 (s), 1268 (m), 1245 (s),
1201 (m), 1160 (m), 1135 (w), 1100 (w), 1085 (m), 1049 (w), 1025
(w), 1016 cm–1 (w).
HRMS (EI): m/z calcd for C23H22O3 (M+): 346.1563; found:
346.1567.
3-Hydroxy-4-methoxybiphenyl-2-carboxylic Acid Methyl Ester
(5g)
Starting from 3a (0.176 g, 1.0 mmol) and 1,4-dimethoxy-1,3-
bis(trimethylsilyloxy)buta-1,3-diene (4g; 0.290 g, 1.0 mmol) in
CH2Cl2 (5 mL), 5g was isolated as a yellow oil (0.046 g, 20%).
1H NMR (300 MHz, CDCl3): d = 1.86 (m, 2 H, CH2), 2.60 (m, 4 H,
3
CH2), 3.38 (s, 3 H, OCH3), 6.38 (s, 1 Harom), 6.55 (d, J = 7.6 Hz,
1 Harom), 7.00–7.20 (m, 9 Harom), 10.79 (s, 1 H, OH).
1H NMR (300 MHz, CDCl3): d = 3.52 (s, 3 H, OCH3), 3.94 (s, 3 H,
OCH3), 6.78 (d, 3J = 8.2 Hz, 1 Harom), 7.01 (d, 3J = 8.3 Hz, 1 Harom),
7.21–7.35 (m, 5 Harom), 10.06 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 51.8, 56.2 (OCH3), 113.5 (Carom),
114.2, 121.5, 126.6, 127.6, 128.2 (CHarom), 135.6, 142.1, 147.5,
150.1 (Carom), 170.8 (C=O).
13C NMR (250 MHz, CDCl3): d = 29.6, 30.8, 35.6 (CH2), 51.7
(OCH3), 111.3 (Carom), 121.7, 125.6, 127.7, 128.2, 128.4, 129.4,
130.1 (CHarom), 132.6 (Carom), 133.8 (CHarom), 141.0, 141.4, 142.3,
159.6 (Carom), 171.5 (C=O).
MS (EI, 70 eV): m/z (%) = 382 (M+, 37Cl, 9), 380 (M+, 35Cl, 29), 244
(35), 209 (100), 97 (23).
MS (EI, 70 eV): m/z (%) = 258 (M+, 49), 227 (22), 226 (100), 225
HRMS (EI): m/z calcd for C23H21ClO3 (M+): 380.1173; found:
(23), 180 (18), 139 (18), 127 (37).
380.1177.
HRMS (EI): m/z calcd for C15H14O4 (M+): 258.0886; found:
258.0892.
4¢-Chloro-3-hydroxy-4-methoxybiphenyl-2-carboxylic Acid
Methyl Ester (5k)
Starting from 3b (0.210 g, 1.0 mmol) and 4g (0.290 g, 1.0 mmol) in
CH2Cl2 (5 mL), 5k was isolated as a yellow oil (0.070 g, 24%).
1H NMR (300 MHz, CDCl3): d = 3.54 (s, 3 H, OCH3), 3.92 (s, 3 H,
OCH3), 6.71 (d, 3J = 8.3 Hz, 1 Harom), 7.00 (d, 3J = 8.3 Hz, 1 Harom),
7.16 (d, 3J = 8.5 Hz, 2 Harom), 7.32 (d, 3J = 8.5 Hz, 2 Harom), 10.20 (s,
1 H, OH).
13C NMR (250 MHz, CDCl3): d = 51.9, 56.1 (OCH3), 113.1 (Carom),
114.2, 121.4, 127.7, 129.6 (CHarom), 132.5, 134.1, 140.7, 147.8,
150.5 (Carom), 170.6 (C=O).
4¢-Chloro-3-hydroxybiphenyl-2-carboxylic Acid Methyl Ester
(5h)
Starting from 1-(4-chlorophenyl)-3-ethoxypropenone (3b; 0.209 g,
1.0 mmol) and 4a (0.260 g, 1.0 mmol) in CH2Cl2 (5 mL), 5h was
isolated as a yellow oil (0.090 g, 35%).
1H NMR (300 MHz, CDCl3): d = 3.46 (s, 3 H, OCH3), 6.69 (d,
3J = 7.5 Hz, 1 Harom), 6.95 (d, 3J = 8.4 Hz, 1 Harom), 7.15 (d, 3J = 8.4
Hz, 2 Harom), 7.33(d, 3J = 8.4 Hz, 2 Harom), 7.40 (dd, 3J = 7.6 Hz, 1
Harom), 10.65 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 51.8 (OCH3), 118.8 (Carom),
117.0, 122.4, 127.7, 129.3 (CHarom), 132.8 (Carom) 133.8 (CHarom),
141.2, 143.5, 161.6 (Carom), 171.0 (C=O).
MS (EI, 70 eV): m/z (%) = 294 (M+, 37Cl, 15), 292 (M+, 35Cl, 45),
262 (433), 261 (26), 260 (100), 231 (25), 225 (56), 217 (22), 197
(19).
MS (EI, 70 eV): m/z (%) = 264 (M+, 37Cl, 12), 262 (M+, 35Cl, 33),
HRMS (EI): m/z calcd for C15H13ClO4 (M+): 292.0496; found:
232 (33), 230 (100), 202 (36), 139 (44).
292.0500.
HRMS (EI): m/z calcd for C14H11ClO3 (M+): 262.0391; found:
262.0396.
3-Hydroxy-4¢-nitrobiphenyl-2-carboxylic Acid Methyl Ester
(5l)
Starting from 3-ethoxy-1-(4-nitrophenyl)propenone (3c; 0.209 g,
1.0 mmol) and 4a (0.260 g, 1.0 mmol) in CH2Cl2 (5 mL), 5l was
isolated as a yellow oil (0.077 g, 30%).
Anal. Calcd for C14H11ClO3: C, 64.01; H, 4.22. Found: C, 63.66; H,
4.27.
4¢-Chloro-4-ethyl-3-hydroxybiphenyl-2-carboxylic Acid Ethyl
Ester (5i)
Starting from 3b (0.420 g, 2.0 mmol) and 4c (0.906 g, 3.0 mmol) in
CH2Cl2 (5 mL), 5i was isolated as a yellow oil (0.150 g, 25%).
IR (neat): 3106 (m), 2959 (w), 2849 (w), 1664 8s), 1603 (s), 1573
(m), 1445 (s), 1439 (s), 1347 (s), 1276, 1216 (s), 1174 (s), 1126 (m),
1108 (m), 1065 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 3.50 (s, 3 H, OCH3), 6.75 (d,
1H NMR (300 MHz, CDCl3): d = 0.81 (t, 3J = 7.1 Hz, 3 H,
3J = 7.5 Hz, 1 Harom), 7.08 (d, 3J = 8.4 Hz, 1 Harom), 7.39 (d, 3J = 8.8
OCH2CH3), 1.25 (t, 3J = 7.5 Hz, 3 H, CH2CH3), 2.72 (q, 3J = 7.5 Hz,
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

2242
G. Mroß et al.
PAPER
Hz, 2 Harom), 7.46 (dd, 3J = 8.2 Hz, 1 Harom), 8.24 (d, 3J = 8.8 Hz, 2
arom), 10.86 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 51.9 (OCH3), 111.2 (Carom),
118.1, 122.1, 122.8, 129.0, 134.1 (CHarom), 142.3, 146.8, 149.6,
162.0 (Carom), 170.5 (C=O).
MS (EI, 70 eV): m/z (%) = 273 (M+, 35), 241 (100), 213 (20), 139
(41).
3J = 7.8 Hz, 2 H, CH2CH2CH3), 3.51 (s, 3 H, OCH3), 3.84 (s, 3 H,
OCH3), 6.72 (d, 3J = 7.6 Hz, 1 Harom), 6.89 (d, 3J = 8.8 Hz, 2 Harom),
7.14 (d, 3J = 8.8 Hz, 2 Harom), 7.25 (d, 3J = 7.6 Hz, 1 Harom), 10.72 (s,
1 H, OH).
13C NMR (250 MHz, CDCl3): d = 14.0 (CH3), 22.5, 31.9 (CH2),
51.7, 55.2 (OCH3), 111.6 (Carom), 113.0, 121.8, 129.2 (CHarom),
129.5 (Carom), 133.7 (CHarom), 135.4, 141.8, 158.4, 159.1 (Carom),
172.0 (C=O).
H
HRMS (EI): m/z calcd for C14H11O5N (M+): 273.0631; found:
273.0631.
MS (EI, 70 eV): m/z (%) = 300 (M+, 80), 268 (76), 240 (56), 239
(100), 237 (35), 139 (18).
3-Hydroxy-4¢-methoxybiphenyl-2-carboxylic Acid Methyl
Ester (5m)
HRMS (EI): m/z calcd for C18H20O4 (M+): 300.1356; found:
300.1352.
Starting from 1-(4-methoxyphenyl)-3-ethoxypropenone (3d;
0.206 g, 1.0 mmol) and 4a (0.260 g, 1.0 mmol) in CH2Cl2 (5 mL),
5m was isolated as a yellow oil (0.080 g, 48%).
3-Hydroxy-3¢-methoxybiphenyl-2-carboxylic Acid Methyl
Ester (5p)
Starting from 1-(3-methoxyphenyl)-3-ethoxypropenone (3e;
0.206 g, 1.0 mmol) and 4a (0.260 g, 1.0 mmol) in CH2Cl2 (5 mL),
5p was isolated as a yellow oil (0.040 g, 20%).
IR (neat): 3172 (w), 3067 (w), 3035 (w), 3010 (w), 2957 (w), 2840
(w), 1709 (w), 1663 (s), 1606 (m), 1570 (m), 1512 (m), 1474 (m),
1434 (s), 1335 (m), 1309 (m), 1261 (m), 1235 (s), 1210 (s), 1176 (s),
1166 (s), 1120 (s), 1095 (m), 1061 (m), 1020 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 3.53 (s, 3 H, OCH3), 3.85 (s, 3 H,
OCH3), 6.79 (d, 3J = 7.5 Hz, 1 Harom), 6.90 (d, 3J = 8.8 Hz, 2 Harom),
6.97 (d, 3J = 8.3 Hz, 1 Harom), 7.16 (d, 3J = 8.8 Hz, 2 Harom), 7.38 (dd,
3J = 8.8 Hz, 1 Harom), 10.53 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 51.7, 55.2 (OCH3), 112.1 (Carom),
113.1, 116.2, 122.6, 129.2, 133.5 (CHarom), 135.0, 144.4, 158.7,
161.2 (Carom), 171.5 (C=O).
MS (EI, 70 eV): m/z (%) = 258 (M+, 43), 227 (17), 226 (100), 198
(30), 183 (22).
IR (neat): 3053 (w), 2999 (w), 2950 (w), 2834 (w), 1733 (w), 1663
(m), 1598 (m), 1571 (m), 1437 (m), 1337 (m), 1321 (m), 1307 (m),
1278 (m), 1225 (s), 1164 (s), 1120 (m), 1101 (m), 1063 (w), 1039
cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.51 (s, 3 H, OCH3), 3.82 (s, 3 H,
OCH3), 6.78–6.89 (m, 4 Harom), 7.00 (d, 3J = 8.3 Hz, 1 Harom), 7.26
(dd, 3J = 7.0 Hz, 1 Harom), 7.40 (dd, 3J = 7.8 Hz, 1 Harom), 10.57 (s, 1
H, OH).
13C NMR (250 MHz, CDCl3): d = 51.7, 55.2 (OCH3), 112.1 (Carom),
112.4, 113.6, 116.7, 120.8, 122.4, 128.5, 133.6 (CHarom), 144.0,
144.6, 159.0, 161.2 (Carom), 171.3 (C=O).
MS (EI, 70 eV): m/z (%) = 258 (M+, 41), 227 (18), 226 (100), 198
(40).
HRMS (EI): m/z calcd for C15H14O4 (M+): 258.0886; found:
258.0886.
3-Hydroxy-4¢-methoxy-4-methylbiphenyl-2-carboxylic Acid
Methyl Ester (5n)
HRMS (EI): m/z calcd for C15H14O4 (M+): 258.0886; found:
258.0881.
Starting from 3d (0.412 g, 2.0 mmol) and 1-methoxy-1,3-bis(trim-
ethylsilyloxy)penta-1,3-diene (4h; 0.822 g, 3.0 mmol) in CH2Cl2 (5
mL), 5n was isolated as a yellow oil (0.260 g, 48%).
4-Hexyl-3-hydroxy-3¢-methoxybiphenyl-2-carboxylic Acid
Methyl Ester (5q)
Starting from 3e (0.206 g, 1.0 mmol) and 1-methoxy-1,3-bis(trime-
thylsilyloxy)deca-1,3-diene (4i; 0.344 g, 1.0 mmol) in CH2Cl2 (5
mL), 5q was isolated as a yellow oil (0.095 g, 30%).
IR (neat): 3028 (w), 2995 (w), 2953 (w), 2934 (w), 2836 (w), 1722
(w), 1662 (s), 1609 (m), 1565 (w), 1517 (m), 1482 (w), 1457 (m),
1436 (s), 1405 (m), 1311 (m), 1298 (m), 1286 (m), 1263 (s), 1237
(s), 1191 (m), 1175 (m), 1142 (m), 1112 (m), 1102 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.52 (s, 3 H,
OCH3), 3.84 (s, 3 H, OCH3), 6.70 (d, 3J = 7.6 Hz, 1 Harom), 6.89 (d,
3J = 8.8 Hz, 2 Harom), 7.14 (d, 3J = 8.8 Hz, 2 Harom), 7.26 (d, 3J = 7.6
Hz, 1 Harom), 10.77 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 15.8 (CH3), 51.7, 55.2 (OCH3),
111.4 (Carom), 113.0, 121.8 (CHarom), 125.2 (Carom), 129.2, 134.4
(CHarom), 135.3, 141.8, 158.4, 159.4 (Carom), 171.9 (C=O).
MS (EI, 70 eV): m/z (%) = 272 (M+, 100), 241 (16), 239 (83), 212
(49), 209 (43), 197 (48), 169 (20), 141 (18), 115 (22).
3
1H NMR (300 MHz, CDCl3): d = 0.77 (t, J = 6.9 Hz, 3 H, CH3),
1.05–1.56 (m, 8 H, CH2), 2.55 (t, 3J = 7.5 Hz, 2 H, CH2), 3.37 (s, 3
H, OCH3), 3.69 (s, 3 H, OCH3), 6.60–6.74 (m, 5 Harom), 7.12 (dd,
3J = 8.2 Hz, 1 Harom), 10.62 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 14.1 (CH3), 22.6, 29.2, 29.3,
29.8, 31.7 (CH2), 51.6, 55.2 (OCH3), 111.5 (Carom), 112.1, 113.6,
120.9, 121.6, 128.4 (CHarom), 130.3 (Carom), 133.6, (CHarom), 141.9,
144.3, 159.0, 159.1 (Carom), 171.8 (C=O).
MS (EI, 70 eV): m/z (%) = 342 (M+, 31), 240 (100).
HRMS (EI): m/z calcd for C21H26O4 (M+): 342.1825; found:
342.1831.
HRMS (EI): m/z calcd for C16H16O4 (M+): 272.1043; found:
272.1039.
3-Hydroxy-3¢,4¢,5¢-methoxybiphenyl-2-carboxylic Acid Isobu-
tyl Ester (5r)
Starting from 3-ethoxy-1-(3,4,5-trimethoxyphenyl)propenone (3f;
0.266 g, 1.0 mmol) and 1-isobutoxy-1,3-bis(trimethylsilyloxy)bu-
ta-1,3-diene (4j; 0.302 g, 1.0 mmol) in CH2Cl2 (5 mL), 5r was iso-
lated as a colorless solid (0.093 g, 31%); mp 90–92 °C.
3-Hydroxy-4¢-methoxy-4-propylbiphenyl-2-carboxylic Acid
Methyl Ester (5o)
Starting from 3d (0.412 g, 2.0 mmol) and 4d (0.906 g, 3.0 mmol) in
CH2Cl2 (5 mL), 5o was isolated as a yellow solid (0.520 g, 86%).
IR (neat): 3008 (w), 2955 (s), 2867 (w), 2839 (w), 1650 (s), 1607
(m), 1577 (w), 1565 (w), 1513 (w), 1433 (s), 1418 (s), 1344 (s),
1301 (m), 1272 (s), 1245 (s), 1218 (s), 1192 (s), 1171 (s), 1147 (s),
1108 (m), 1101 (m), 1071 cm–1 (w).
IR (neat): 2996 (w), 2961 (w), 2937 (w), 2874 (w), 2837 (w), 1644
(m), 1599 (w), 1582 (m), 1510 (w), 1462 (m), 1446 (m), 1432 (w),
1410 (m), 1380 (m), 1354 (m), 1310 (w), 1288 (m), 1250 (s), 1237
(s), 1212 (m), 1179 (m), 1123 (s), 1107 (s), 1063 (w), 1044 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 0.99 (t, 3J = 7.4 Hz, 3 H,
3
CH2CH2CH3), 1.67 (sext, J = 7.6 Hz, 2 H, CH2CH2CH3), 2.66 (t,
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Salicylates
2243
1H NMR (300 MHz, CDCl3): d = 0.62 [d, 3J = 6.7 Hz, 6 H,
(0.01 mmol) was stirred for 14 h in a pressure tube at 60 °C. To the
mixture was added aq NH4Cl (20 mL) and the mixture was extract-
ed with Et2O (3 × 10 mL). The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The
residue was purified by chromatography (silica gel, heptanes–
EtOAc, 20:1) to give 7 as a colorless solid (0.043 g, 50%); mp 140–
150 °C.
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.52 (s, 3 H,
OCH3), 3.84 (s, 3 H, OCH3), 6.70 (d, 3J = 7.6 Hz, 1 Harom), 6.89 (d,
3J = 8.8 Hz, 2 Harom), 7.14 (d, 3J = 8.8 Hz, 2 Harom), 7.26 (d, 3J = 7.6
Hz, 1 Harom), 10.77 (s, 1 H, OH).
3
CH(CH3)2], 1.45 [tq, J = 6.7 Hz, 1 H, CH2CH(CH3)2], 3.80 [d,
3J = 6.5 Hz, 2 H, CH2CH(CH3)2], 3.83 (s, 6 H, OCH3), 3.80 (s, 3 H,
3
OCH3), 6.46 (s, 2 Harom), 6.80 (d, J = 7.5 Hz, 1 Harom), 7.00 (d,
3J = 8.3 Hz, 1 Harom), 7.39 (dd, 3J = 7.6 Hz, 1 Harom), 10.77 (s, 1 H,
OH).
13C NMR (250 MHz, CDCl3): d = 18.8 [CH(CH3)2], 27.2
[CH(CH3)2], 56.1, 60.7 (OCH3), 71.8 [CH2CH(CH3)2], 105.6
(CHarom), 112.3 (Carom), 117.7, 122.4, 133.4 (CHarom), 137.1, 138.7,
144.5, 152.7, 161.4 (Carom), 171.1 (C=O).
MS (EI, 70 eV): m/z (%) = 360 (M+, 95), 286 (100), 177 (45).
HRMS (EI): m/z calcd for C20H24O6 (M+): 360.1567; found:
13C NMR (250 MHz, CDCl3): d = 51.7 (OCH3), 127.5, 128.2,
128.3, 128.8, 129.3 (CHarom), 132.8, 140.3, 140.5 (Carom), 169.8
(C=O).
360.1562.
3-Hydroxy-3¢,4¢,5¢-trimethoxy-4-(3-phenylpropyl)biphenyl-2-
carboxylic Acid Methyl Ester (5s)
MS (EI, 70 eV): m/z (%) = 288 (M+, 52), 258 (20), 257 (100), 228
(28), 226 (16).
Starting from 3f (0.266 g, 1.0 mmol) and 4f (0.378 g, 1.0 mmol) in
CH2Cl2 (5 mL), 5s was isolated as a yellow oil (0.160 g, 37%).
HRMS (EI): m/z calcd for C20H16O2 (M+): 288.1144; found:
288.1141.
IR (neat): 3060 (w), 3025 (w), 2999 (m), 2936 (m), 2858 (w), 2836
(w), 1663 (s), 1585 (s), 1510 (m), 1496 (m), 1437 (s), 1409 (s), 1351
(s), 1285 (m), 1252 (s), 1195 (m), 1168 (m), 1127 (s), 1008 cm–1
(m).
Bromination of 3a,e to 8a,b
To a CH2Cl2 solution (5 mL) of 3a,e (2.0 mmol) was slowly added
a CH2Cl2 solution (5 mL) of Br2 (2.0 mmol) at 0 °C using a drop-
ping funnel. After stirring for 1 h, H2O (20 mL) was added, the or-
ganic and the aqueous layer were separated and the latter was
extracted with CH2Cl2 (3 × 20 mL). The combined organic layers
were dried (Na2SO4), filtered, and the filtrate was concentrated in
vacuo. The residue was purified by chromatography (silica gel, hep-
tanes–EtOAc, 10:1).
1H NMR (300 MHz, CDCl3): d = 1.99 (m, 2 H, CH2), 2.73 (m, 4 H,
CH2), 3.54 (s, 3 H, OCH3), 3.84 (s, 6 H, OCH3), 3.89 (s, 3 H, OCH3),
3
6.44 (s, 2 Harom), 6.76 (d, J = 7.6 Hz, 1 Harom), 7.16–7.32 (m, 6
Harom), 10.70 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 30.0, 31.2, 36.0 (CH2), 52.2,
56.5, 61.3 (OCH3), 105.9 (CHarom), 112.2 (Carom), 122.0, 126.1,
128.6, 128.8 (CHarom), 130.1 (Carom), 134.1 (CHarom), 137.3, 139.0,
142.6, 142.7, 153.0, 159.5 (Carom), 172.2 (C=O).
MS (EI, 70 eV): m/z (%) = 436 (M+, 100), 300 (91), 269 (87).
HRMS (EI): m/z calcd for C26H28O6 (M+): 436.1880; found:
6-Bromo-3-hydroxybiphenyl-2-carboxylic Acid Ethyl Ester
(9a)
The reaction was carried out following the typical procedure as giv-
en for the synthesis of 5a–t. Starting from 3a (0.253 g, 1.0 mmol)
and 4a (0.260 g, 1.0 mmol) in CH2Cl2 (5 mL), 9a was prepared via
the intermediate bromide 8a as a yellow solid (0.122 g, 50%),
mp 68–70 °C.
436.1879.
1-(3-Hydroxy-3¢,4¢,5¢-trimethoxy-4-methylbiphenyl-2-yl)pro-
pan-1-one (5t)
Starting from 3f (0.266 g, 1.0 mmol) and 3,5-bis(trimethylsily-
loxy)hepta-2,4-diene (4k; 0.272 g, 1.0 mmol) in CH2Cl2 (5 mL), 5t
was isolated as a brownish solid (0.040 g, 12%); mp 68–70 °C.
IR (neat): 3070 (w), 3024 (w), 3000 (w), 2947 (w), 2849 (w), 1662
(s), 1589 (m), 1537 (w), 1496 (w), 1433 (s), 1332 (s), 1282 (m),
1228 (m), 1205 (s), 1134 (m), 1114 (m), 1092 (m), 1070 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 3.39 (s, 3 H, OCH3), 6.93 (d,
3J = 8.9 Hz, 1 Harom), 7.09–7.13 (m, 2 Harom), 7.34–7.43 (m, 3 Harom),
7.68 (d, 3J = 7.6 Hz, 1 Harom), 10.78 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 52.0 (OCH3), 114.3, 114.6
(Carom), 118.7, 127.1, 127.6, 128.3, 138.0 (CHarom), 141.7, 143.6,
160.8 (Carom), 170.5 (C=O).
MS (EI, 70 eV): m/z (%) = 308 (M+, 81Br, 32), 306 (M+, 79Br, 31),
276 (100), 274 (94), 249 (20), 246 (23), 139 (64).
HRMS (EI): m/z calcd for C14H11BrO3 (M+): 305.9886; found:
305.9889.
IR (neat): 3443 (br), 2938 (s), 2837 (w), 1628 (s), 1584 (s), 1508 (s),
1462 (s), 1379 (m), 1351 (m), 1267 (s), 1238 (s), 1183 (w), 1166
(m), 1128 (s), 1049 (m), 1007 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.90 (t, 3J = 7.6 Hz, 3 H,
CH2CH3), 2.18 (q, 3J = 7.6 Hz, 2 H, CH2CH3), 2.29 (s, 3 H, CH3),
3.86 (s, 6 H, OCH3), 3.89 (s, 3 H, OCH3), 6.51 (s, 2 Harom), 6.80 (d,
3
3J = 7.6 Hz, 1 Harom), 7.14 (d, J = 7.6 Hz, 1 Harom), 11.02 (s, 1 H,
OH).
13C NMR (250 MHz, CDCl3): d = 9.5 (CH2CH3), 15.8 (CH3), 36.2
(CH2CH3), 56.1, 61.0 (OCH3), 106.1, 121.0 (CHarom), 126.1 (Carom),
134.1 (CHarom), 137.7, 137.8, 141.3, 153.3, 158.0 (Carom), 211.2
(C=O).
MS (EI, 70 eV): m/z (%) = 330 (M+, 100), 301 (38), 299 (21), 286
(15), 271 (16), 270 (58).
6-Bromo-3-hydroxy-4¢-methoxybiphenyl-2-carboxylic Acid
Ethyl Ester (9b)
The reaction was carried out following the typical procedure as giv-
en for the synthesis of 5a–t. Starting from 3a (0.284 g, 1.0 mmol)
and 4h (0.274 g, 1.0 mmol) in CH2Cl2 (5 mL), 9b was prepared via
the intermediate bromide 8a as a yellow solid (0.060 g, 22%);
mp 96–98 °C.
HRMS (EI): m/z calcd for C19H22O5 (M+): 330.1461; found:
330.1461.
IR (neat): 3211 (br), 3088 (w), 3030 (w), 2997 (w), 2960 (w), 2935
(w), 2838 (w), 1892 (w), 1693 (s), 1608 (m), 1570 (m), 1514 (m),
1464 (m), 1434 (s), 1392 (m), 1370 (m), 1339 (m), 1312 (m), 1286
(s), 1225 (s), 1171 (s), 1141 (m), 1116 (m), 1104 (m), 1086 (m),
1031 (s), 1007 cm–1 (m).
[1,1¢;3¢,1¢¢]Terphenyl-2-carboxylic Acid Methyl Ester (7)
To a CH2Cl2 solution (3 mL) of 5a (0.070 g, 0.3 mmol) were slowly
added pyridine and Tf2O (0.36 mmol) at –78 °C. The mixture was
stirred for 4 h and subsequently purified by chromatography (silica
gel, CH2Cl2) to give 6. A dioxane solution (5 mL) of 6 (0.29 mmol),
PhB(OH)2 (0.37 mmol), anhyd K3PO4 (0.46 mmol), and Pd(PPh3)
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

2244
G. Mroß et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 0.76 (t, 3J = 7.1 Hz, 3 H,
OCH2CH3), 3.85 (s, 3 H, OCH3), 3.91 (q, 3J = 7.1 Hz, 2 H,
layers were dried (Na2SO4), filtered, and the filtrate was concentrat-
ed in vacuo. The residue was purified by chromatography (silica
gel, length = 5 cm, diameter = 1 cm, EtOAc–heptanes, 1:5).
3
OCH2CH3), 6.89–6.92 (m, 4 Harom), 7.04 (d, J = 8.8 Hz, 1 Harom),
7.66 (d, 3J = 8.9 Hz, 1 Harom), 10.86 (s, 1 H, OH).
1-Hydroxyfluoren-9-one (10a)
13C NMR (250 MHz, CDCl3): d = 13.0 (OCH2CH3), 55.2 (OCH3),
61.3 (OCH2CH3), 113.0 (CH, Ar), 114.8, 115.2 (Carom), 118.5, 129.6
(CHarom), 134.4 (Carom), 137.8 (CHarom), 143.4, 158.8, 160.8 (Carom),
170.2 (C=O).
Starting from 3-hydroxybiphenyl-2-carboxylic acid methyl ester
(5a; 0.060 g, 0.26 mmol), 10a was isolated as a brownish solid
(0.041 g, 81%); mp 100–105 °C.
IR (KBr): 3354 (br), 3044 (w), 2956 (w), 2920 (w), 2850 (w), 1952
(w), 1926 (w), 1895 (w), 1861 (w), 1823 (w), 1682 (s), 1615 (m),
1595 (s), 1587 (s), 1482 (w), 1467 (s), 1453 (s), 1436 (s), 1381 (w),
1321 (m), 1306 (m), 1282 (s), 1203 (s), 1168 (s), 1161 (s), 1129 (s),
1107 (s), 1073 (s), 1037 cm–1 (s).
MS (EI, 70 eV): m/z (%) = 352 (M+, 81Br, 33), 350 (M+, 79Br, 33),
307 (16), 306 (99), 305 (17), 304 (100), 169 (15).
HRMS (EI): m/z calcd for C16H15BrO4 (M+): 350.0148; found:
350.0149.
1H NMR (300 MHz, CDCl3): d = 6.75 (d, 3J = 8.4 Hz, 1 Harom), 7.02
6-Bromo-3-hydroxy-4-methylbiphenyl-2-carboxylic Acid
Methyl Ester (9c)
The reaction was carried out following the typical procedure as giv-
en for the synthesis of 5a–t. Starting from 3e (0.423 g, 1.5 mmol)
and 4h (0.411 g, 1.5 mmol) in CH2Cl2 (5 mL), 9c was prepared via
the intermediate bromide 8b as a yellow oil (0.166 g, 52%).
3
(d, J = 7.1 Hz, 1 Harom), 7.26–7.38 (m, 2 Harom), 7.47–7.51 (m, 2
H
arom), 7.62 (d, 3J = 7.3 Hz, 1 Harom).
13C NMR (250 MHz, CDCl3): d = 112.8 (CHarom), 117.4 (C, Ar),
118.1, 121.0, 124.0, 129.0 (CHarom), 134.2 (C, Ar), 134.6, 137.4
(CHarom), 143.8, 144.1, 157.3 (C, Ar), 196.3 (C=O).
IR (neat): 3057 (w), 3024 (w), 2950 (w), 2924 (w), 2851 (w), 1661
(s), 1599 (w), 1567 (w), 1498 (w), 1435 (m), 1402 (m), 1378 (w),
1355 (m), 1287 (m), 1235 (s), 1195 (s), 1161 (s), 1072 (w), 1016
cm–1 (m).
MS (EI, 70 eV): m/z (%) = 196 (M+, 100), 168 (52), 139 (42).
HRMS (EI): m/z calcd for C13H8O2 (M+): 196.0518; found:
196.0522.
1H NMR (300 MHz, CDCl3): d = 2.13 (s, 3 H, CH3), 3.21 (s, 3 H,
1-Hydroxy-2-octylfluoren-9-one (10b)
OCH3), 6.92–7.25 (m, 5 Harom), 7.41 (s, 1 Harom), 10.85 (s, 1 H, OH).
Starting from 3-hydroxy-4-octylbiphenyl-2-carboxylic acid methyl
ester (5e; 0.274 g, 0.80 mmol), 10b was isolated as an orange solid
(0.210 g, 84%); mp 18–22 °C.
13C NMR (250 MHz, CDCl3): d = 15.6 (CH3), 51.9 (OCH3), 113.5,
113.9 (Carom), 127.0, 127.5 (CHarom), 128.2 (Carom), 128.6, 138.5
(CHarom), 141.0, 142.0, 159.2 (Carom), 170.9 (C=O).
MS (EI, 70 eV): m/z (%) = 322 (M+, 81Br, 33), 320 (M+, 79Br, 36),
290 (80), 289 (19), 288 (81), 210 (18), 209 (100), 153 (27), 152
(51).
IR (KBr): 3367 (w), 2921 (s), 2852 (s), 1712 (m), 1685 (s), 1651
(w), 1622 (m), 1600 (m), 1576 (w), 1466 (s), 1455 (s), 1435 (m),
1371 (m), 1348 (m), 1318 (m), 277 (m), 1171 (s), 1125 (m), 1108
(m), 1038 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 0.87 [t, 3J = 6.8 Hz, 3 H,
CH2(CH2)6CH3], 1.17–1.63 [m, 12 H, CH2(CH2)6CH3], 2.59 [t,
HRMS (EI): m/z calcd for C15H13BrO3 (M+): 320.0042; found:
320.0034.
3
3J = 7.6 Hz, 2 H, CH2(CH2)6CH3], 6.94 (d, J = 7.2 Hz, 1 Harom),
3
7.16–7.27 (m, 2 Harom), 7.45 (d, J = 3.8 Hz, 2 Harom), 7.60 (d,
6-Bromo-3-hydroxy-4¢-methoxy-4-methylbiphenyl-2-carboxyl-
ic Acid Methyl Ester (9d)
3J = 7.3 Hz, 1 Harom).
The reaction was carried out following the typical procedure as giv-
en for the synthesis of 5a–t. Starting from 3e (0.284 g, 1.0 mmol)
and 4l (0.274 g, 1.0 mmol) in CH2Cl2 (5 mL), 9d was prepared via
the intermediate bromide 8b as a yellow solid (0.160 g, 48%);
mp 83–85 °C.
13C NMR (250 MHz, CDCl3): d = 14.0 (CH3), 22.6, 27.4, 29.2,
29.7, 31.7, 31.8, 30.9 (CH2), 112.5 (CHarom), 117.2 (Carom), 120.6,
123.9, 128.5, (CHarom), 132.8 (Carom), 134.5, 137.1 (CHarom), 141.3,
144.4, 155.9, 196.8 (Carom), 213.6 (C=O).
MS (EI, 70 eV): m/z (%) = 308 (M+, 33), 290 (20), 210 (78), 209
IR (neat): 3032 (w), 3003 (w), 2955 (w), 2923 (w), 2837 (w), 1713
(w), 1655 (m), 1606 (m), 1513 (m), 1462 (m), 1429 (m), 1401 (m),
1377 (m), 1337 (m), 1308 (m), 1283 (m), 1240 (s), 1228 (s), 1191
(m), 1174 (m), 1156 (m), 1145 (m), 1108 (m), 1018 cm–1 (s).
(100).
HRMS (EI): m/z calcd for C21H24O2 (M+): 308.1770; found:
308.1764.
1H NMR (300 MHz, CDCl3): d = 2.28 (s, 3 H, CH3), 3.43 (s, 3 H,
OCH3), 3.85 (s, 3 H, OCH3), 6.91 (d, 3J = 8.8 Hz, 2 Harom), 7.03 (d,
3J = 8.8 Hz, 2 Harom), 7.56 (s, 1 Harom), 10.91 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 15.6 (CH3), 52.1, 55.1 (OCH3),
112.9 (CHarom), 113.8, 114.5, 127.9 (C, Ar), 129.7 (CHarom), 134.3
(C, Ar), 138.3 (CHarom), 140.6, 158.5, 159.0 (C, Ar), 171.1 (C=O).
MS (EI, 70 eV): m/z (%) = 352 (M+, 81Br, 47), 350 (M+, 79Br, 47),
321 (16), 320 (99), 319 (22), 318 (100), 240 (19), 239 (95), 168
(16), 139 (29).
1-Hydroxy-2-propylfluoren-9-one (10c)
Starting from 3-hydroxy-4-propylbiphenyl-2-carboxylic acid meth-
yl ester (5d; 0.260 g, 0.96 mmol), 10c was isolated as a yellow solid
(0.220 g, 96%); mp 50–52 °C.
IR (KBr): 3341 (w), 3054 (w), 2949 (m), 2927 (s), 2927 (m), 2902
(m), 2865 (m), 1677 (s), 1625 (m), 1598 (s), 1556 (w), 1537 (w),
1495 (w), 1467 (m), 1453 (m), 1431 (s), 1345 (s), 1293 (m), 1293
(m), 1262 (m), 1238 (m), 1197 (s), 1168 (s), 1160 (m), 1146 (m),
1104 (m), 1073 (m), 1013 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.98 (t, 3J = 7.3 Hz, 3 H,
HRMS (EI): m/z calcd for C16H15BrO4 (M+): 350.0148; found:
350.0150.
3
CH2CH2CH3), 1.65 (sext, J = 7.6 Hz, 2 H, CH2CH2CH3), 2.59 (t,
3J = 7.2 Hz, 2 H, CH2CH2CH3), 6.95 (d, 3J = 7.2 Hz, 1 Harom), 7.17–
7.28 (m, 2 Harom), 7.45 (d, 3J = 4.6 Hz, 2 Harom), 7.61 (d, 3J = 7.3 Hz,
1 Harom).
Fluorenones 10a–e; General Procedure
To 5a,e,d,k, or 9b (0.25 mmol) was added concd H2SO4 (3 mL) at
0 °C and the mixture was stirred for 1–24 h until the conversion was
complete (TLC control). The mixture was poured into ice water (50
mL) and extracted with CH2Cl2 (3 × 10 mL). The combined organic
13C NMR (250 MHz, CDCl3): d = 13.8 (CH3), 22.7, 30.9 (CH2),
112.5 (CHarom), 117.1 (Carom), 120.6, 123.9, 128.5, (CHarom), 132.5,
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

PAPER
Synthesis of Functionalized Salicylates
2245
134.3 (Carom), 134.5, 137.1 (CHarom), 141.3, 144.3, 155.8 (Carom),
196.7 (C=O).
0.274 g, 1.0 mmol) in CH2Cl2 (5 mL), 13a was isolated (0.080 g,
40%) as a colorless solid; mp 38–41 °C.
MS (EI, 70 eV): m/z (%) = 238 (M+, 34), 210 (19), 209 (100), 152
(29).
HRMS (EI): m/z calcd for C16H14O2 (M+): 238.0988; found:
238.0991.
IR (neat): 3031 (w), 2962 (m), 2905 (w), 1667 (m), 1616 (w), 1585
(w), 1447 (w), 1411 (w), 1380 (w), 1347 (w), 1289 (w), 1259 (s),
1196 (w), 1147 (m), 1095 (s), 1054 (s), 1023 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 2.21 (s, 3 H, CH3), 2.50 (s, 3 H,
3
CH3), 3.95 (s, 3 H, OCH3), 6.55 (d, J = 7.5 Hz, 1 Harom), 7.08 (d,
7-Chloro-1-hydroxy-2-methoxyfluoren-9-one (10d)
Starting from 4¢-chloro-3-hydroxy-4-methoxybiphenyl-2-carboxyl-
ic acid methyl ester (5k; 0.060 g, 0.20 mmol), 10d was isolated as a
red solid (0.050 g, 96%); mp 150–152 °C.
3J = 7.5 Hz, 1 Harom), 11.55 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 15.7, 23.8 (CH3), 52.0 (OCH3),
111.5 (Carom), 122.0 (CHarom), 124.1 (Carom), 135.0 (CHarom), 138.4,
161.0 (Carom), 172.6 (C=O).
IR (KBr): 3408 (m), 3093 (w), 2945 (w), 2919 (w), 2849 (w), 2832
(w), 1731 (w), 1681 (s), 1651 (m), 1621 (m), 1593 (m), 1557 (w),
1497 (m), 1463 (s), 1456 (s), 1438 (s), 1423 (s), 1360 (w), 1320 (w),
1296 (s), 1280 (s), 1239 (s), 1212 (s), 1193 (s), 1166 (s), 1116 (s),
1086 (s), 1073 (s), 1055 (s), 1012 cm–1 (s).
MS (EI, 70 eV): m/z (%) = 180 (M+, 47), 149, (23), 148 (91), 120
(100), 91 (50).
HRMS (EI): m/z calcd for C10H12O3 (M+): 180.0781; found:
180.0785.
1H NMR (300 MHz, CDCl3): d = 3.84 (s, 3 H, OCH3), 6.77 (d,
3J = 7.8 Hz, 1 Harom), 6.86 (d, 3J = 7.8 Hz, 1 Harom), 7.28 (d,
3J = 8.0 Hz, 1 Harom), 7.34 (d, 3J = 8.0 Hz, 1 Harom), 7.49 (d, 4J = 1.8
Hz, 1 Harom).
13C NMR (250 MHz, CDCl3): d = 55.4 (OCH3), 112.8, 116.6
(CHarom), 118.1 (Carom), 121.3, 124.3 (CHarom), 133.8, 133.8 (Carom),
134.2 (CHarom), 136.0, 142.6, 147.5, 149.6, (Carom), 194.2 (C=O).
MS (EI, 70 eV): m/z (%) = 262 (M+, 37Cl, 33), 260 (M+, 35Cl, 98),
231 (38), 219 (34), 217 (100), 214 (29), 126 (35).
HRMS (EI): m/z calcd for C14H9ClO3 (M+): 260.0234; found:
260.0232.
2-Hydroxy-3-methoxy-6-methylbenzoic Acid Methyl Ester
(13b)
Starting from 4-methoxybut-3-en-2-one (11a; 0.100 g, 1.0 mmol)
and 1,4-dimethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (4g;
0.290 g, 1.0 mmol) in CH2Cl2 (5 mL), 13b was isolated as a yellow
oil (0.075 g, 38%).
IR (neat): 3432 (w), 3031 (w), 3000, w), 2955 (m), 2937 (m), 2837
(w), 1730 (m), 1663 (s), 1617 (w), 1583 (m), 1492 (m), 1436 (s),
1384 (w), 1351 (m), 1323 (m), 1294 (s), 1246 (s), 1201 (m), 1172
(w), 1154 (m), 1067 (s), 1047 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 2.46 (s, 3 H, CH3), 3.87 (s, 3 H,
OCH3), 3.96 (s, 3 H, OCH3), 6.46 (d, 3J = 8.2 Hz, 1 Harom), 6.89 (d,
3J = 8.2 Hz, 1 Harom), 11.27 (s, 1 H, OH).
4-Bromo-1-hydroxy-2-methylfluoren-9-one (10e)
Starting from 6-bromo-3-hydroxy-4-methyl-biphenyl-2-carboxylic
acid methyl ester (9b; 0.120 g, 0.38 mmol), 10e was isolated as a
yellow solid (0.090 g, 82%); mp 130–135 °C.
13C NMR (250 MHz, CDCl3): d = 23.1 (CH3), 52.1, 56.1 (OCH3),
112.7 (Carom), 115.3, 121.3 (CHarom), 131.6, 146.6, 152.5 (Carom),
172.1 (C=O).
IR (KBr): 3316 (m), 3064 (w), 3050 (w), 2947 (w), 2929 (m), 2853
(w), 2731 (m), 1679 (s), 1620 (s), 1600 (s), 1583 (s), 1557 (w), 1485
(m), 1464 (s), 1444 (s), 1419 (s), 1377 (w), 1351 (s), 1309 (m), 1276
(s), 1236 (s), 1197 (m), 1168 (s), 1112 (s), 1078 (m), 1032 (s), 1012
cm–1 (m).
MS (EI, 70 eV): m/z (%) = 196 (M+, 60), 165 (40), 164 (100), 163
(17), 136 (90), 135 (45), 134 (29), 121 (41).
HRMS (EI): m/z calcd for C10H12O4 (M+): 196.0730; found:
196.0733.
1H NMR (300 MHz, CDCl3): d = 2.21 (s, 3 H, CH3), 7.26–7.34 (m,
Anal. Calcd for C10H12O4: C, 61.22; H, 6.16. Found: C, 61.03; H,
6.34.
3
3
2 Harom), 7.52 (dd, J = 7.6 Hz, 1 Harom), 7.64 (d, J = 7.8 Hz, 1
Harom), 8.2 (d, 3J = 7.6 Hz, 1 Harom).
1-(2-Hydroxy-6-methylphenyl)ethanone (13c)
Starting from 4-methoxybut-3-en-2-one (11a; 0.100 g, 1.0 mmol)
and 2,4-bis(trimethylsilyloxy)penta-1,3-diene (4m; 0.244 g,
1.0 mmol) in CH2Cl2 (5 mL), 13c was isolated as a yellow oil
(0.050 g, 33%).
13C NMR (250 MHz, CDCl3): d = 14.4 (CH3), 107.2, 118.6 (Carom),
123.3, 124.0, 128.9 (CHarom), 130.4, 134.1 (Carom), 134.7 (CHarom),
138.6 (Carom), 141.4 (CHarom), 143.3, 155.4, (Carom), 195.6 (C=O).
MS (EI, 70 eV): m/z (%) = 290 (M+, 81Br, 97), 288 (M+, 79Br, 100),
209 (81), 152 (31).
HRMS (EI): m/z calcd for C14H9BrO2 (M+): 287.9780; found:
287.9773.
IR (neat): 3342 (b), 3061 (w), 2964 (w), 2929 (w), 2855 (w), 1688
(m), 1624 (s), 1606 (s), 1464 (s), 1446 (s), 1381 (m), 1361 (m), 1326
(s), 1287 (s), 1255 (s), 1213 (s), 1165 (m), 1101 (w), 1055 (w), 1034
cm–1 (w).
Salicylate Esters 13a–n; General Procedure
1H NMR (300 MHz, CDCl3): d = 2.60 (s, 3 H, CH3), 2.67 (s, 3 H,
To a CH2Cl2 solution (1 mL) of 4 (3.0 mmol) and 11 or 12 (2.0
mmol) was added a CH2Cl2 solution (1 mL) of TiCl4 (0.24 mL, 2.0
mmol) at –78 °C. The solution was allowed to warm to 20 °C during
14 h with stirring. To the solution were added CH2Cl2 (10 mL) and
aq 10% HCl (10 mL). The organic and the aqueous layers were sep-
arated and the latter was extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were dried (Na2SO4), filtered, and the fil-
trate was concentrated in vacuo. The residue was purified by chro-
matography (heptanes–EtOAc, 10:1).
3
3
CH3), 6.72 (d, J = 7.7 Hz, 1 Harom), 6.84 (d, J = 8.3 Hz, 1 Harom),
7.27 (t, 3J = 8.0 Hz, 1 Harom), 12.29 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 24.4, 33.3 (CH3), 116.5 (CHarom),
121.6, (Carom), 123.0, 134.6 (CHarom), 139.4, 162.7 (Carom), 206.1
(C=O).
MS (EI, 70 eV): m/z (%) = 150 (M+, 35), 135 (100).
HRMS (EI): m/z calcd for C9H10O2 (M+): 150.0675; found:
150.0678.
2-Hydroxy-3,6-dimethylbenzoic Acid Methyl Ester (13a)
Starting from 4-methoxybut-3-en-2-one (11a; 0.100 g, 1.0 mmol)
and 1-methoxy-1,3-bis(trimethylsilyloxy)penta-1,3-diene (4h;
2-Hydroxy-6-methylbenzoic Acid 2-Methoxyethyl Ester (13d)
Starting from 4-methoxybut-3-en-2-one (11a; 0.100 g, 1.0 mmol)
and 1-(2-methoxyethoxy)-1,3-bis(trimethylsilyloxy)buta-1,3-di-
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

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G. Mroß et al.
PAPER
ene (4b; 0.304 g, 1.0 mmol) in CH2Cl2 (5 mL), 13d was isolated as
HRMS (EI): m/z calcd for C15H22O3 (M+): 250.1563; found:
a yellow oil (0.051 g, 24%).
250.1567.
IR (neat): 3408 (w), 3058 (w), 2971 (m), 2933 (m), 2892 (m), 2822
(w), 1730 (w), 1661 (s), 1608 (m), 1579 (m), 1459 (m), 1445 (m),
1407 (w), 1376 (m), 1292 (m), 1253 (s), 1215 (s), 1166 (m), 1120
(s), 1079 (m), 1033 cm–1 (w).
6-Ethyl-2-hydroxy-3-methylbenzoic Acid Methyl Ester (13g)
Starting from 1-methoxypent-1-en-3-one (11b; 0.228 g, 2.0 mmol)
and 1-methoxy-1,3-bis(trimethylsilyloxy)penta-1,3-diene (4h;
0.822 g, 3.0 mmol) in CH2Cl2 (5 mL), 13g was isolated as a mixture
of regioisomers (rs = 4:1, 0.115 g, 30%). The spectroscopic data are
listed for the major isomer.
1H NMR (300 MHz, CDCl3): d = 2.56 (s, 3 H, CH3), 3.42 (s, 3 H,
3
3
OCH3), 3.73 (t, J = 4.7 Hz, 2 H, CH2), 4.51 (t, J = 4.7 Hz, 2 H,
CH2), 6.71 (d, J = 8.1 Hz, 1 Harom), 6.83 (d, 3J = 8.8 Hz, 1 Harom),
3
IR (neat): 3152 (w), 2966 (w), 2953 (w), 2875 (w), 1728 (w), 1668
(s), 1617 (m), 1575 (w), 1497 (w), 1438 (s), 1416 (m), 1378 (m),
1438 (s), 1281 (s), 1262 (s), 1242 (s), 1233 (s), 1195 (s), 1174 (m),
1149 (s), 1102 (m), 1093 (m), 1058 (w), 1031 (m), 1010 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.19 (t, 3J = 7.5 Hz, 3 H,
CH2CH3), 2.21 (s, 3 H, CH3), 2.65 (q, 3J = 7.5 Hz, 2 H, CH2CH3),
3.92 (s, 3 H, OCH3), 6.70 (d, 3J = 8.2 Hz, 1 Harom), 7.62 (d, 3J = 8.2
Hz, 1 Harom), 11.08 (s, 1 H, OH).
7.26 (t, 3J = 3.9 Hz, 1 Harom), 11.07 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 23.8 (CH3), 58.9 (OCH3), 64.1,
70.0 (CH2), 112.4 (Carom), 115.5, 122.9, 134.2 (CHarom), 141.5,
162.6 (Carom), 171.3 (C=O).
MS (EI, 70 eV): m/z (%) = 210 (M+, 21), 135 (30), 134 (100).
HRMS (EI): m/z calcd for C11H14O4 (M+): 210.0886; found:
210.0890.
13C NMR (250 MHz, CDCl3): d = 10.6 (CH3), 14.1 (CH2CH3), 27.0
(CH2CH3), 62.0 (OCH3), 109.3 (Carom), 119.0 (CHarom), 123.9
(Carom), 126.7 (CHarom), 150.7, 159.8 (Carom), 171.0 (C=O).
MS (EI, 70 eV): m/z (%) = 194 (M+, 38), 163 (21), 162 (100), 134
(50).
HRMS (EI): m/z calcd for C11H14O3 (M+): 194.0937; found:
194.0945.
3-Chloro-2-hydroxy-6-methylbenzoic Acid Ethyl Ester (13e)
Starting from 4-methoxybut-3-en-2-one (11a; 0.100 g, 1.0 mmol)
and
4-chloro-1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(4n; 0.214 g, 1.0 mmol) in CH2Cl2 (5 mL), 13e was isolated
(0.032 g, 15%) as a yellow solid; mp 54–56 °C.
IR (neat): 3430 (w), 3301 (w), 3065 (w), 3009 (w), 2985 (m), 2939
(m), 2870 (w), 2822 (w), 2744 (w), 2624 (w), 2586 (w), 1911 (w),
1662 (s), 1600 (m), 1564 (w), 1468 (m), 1455 (m), 1424 (s), 1374
(s), 1344 (m), 1298 (s), 1254 (s), 1209 (s), 1160 (m), 1126 (m) 1108
(m), 1020 cm–1 (s).
1H NMR (300 MHz, CDCl3): d = 1.44 (t, 3J = 7.1 Hz, 3 H,
OCH2CH3), 2.63 (s, 3 H, CH3), 4.46 (t, 3J = 7.1 Hz, 2 H, OCH2CH3),
6.67 (d, 3J = 8.1 Hz, 1 Harom), 7.37 (d, 3J = 8.1 Hz, 1 Harom), 11.93 (s,
1 H, OH).
13C NMR (250 MHz, CDCl3): d = 14.1 (CH3), 23.8 (OCH2CH3),
62.1 (OCH2CH3), 113.6, 119.9 (Carom), 122.8, 134.0 (CHarom),
140.0, 158.1 (Carom), 171.4 (C=O).
MS (EI, 70 eV): m/z (%) = 216 (M+, 37Cl, 8), 214 (M+, 35Cl, 22), 169
(24), 168 (100).
2-Hydroxy-3-methyl-6-propylbenzoic Acid Methyl Ester (13h)
Starting from 1-ethoxyhex-1-en-3-one (11c; 0.284 g, 2.0 mmol)
and 1-methoxy-1,3-bis(trimethylsilyloxy)penta-1,3-diene (4h;
0.822 g, 3.0 mmol) in CH2Cl2 (5 mL), 13h was isolated as a yellow
oil (0.080 g, 18%).
IR (neat): 3151 (w), 2955 (m), 2932 (w), 2817 (w), 1727 (w), 1668
(s), 1616 (m), 1575 (w), 1497 (w), 1438 (s), 1413 (m), 1378 (m),
1328 (m), 1282 (m), 1271 (m), 1247 (s), 1195 (s), 1175 (m), 1149
(s), 1106 (m), 1045 (w), 1009 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 0.97 (t, 3J = 7.3 Hz, 3 H,
CH2CH3), 1.59 (sext, 3J = 7.7 Hz, 2 H, CH2CH2CH3), 2.20 (s, 3 H,
CH3), 2.60 (t, 3J = 7.6 Hz, 2 H, CH2CH2CH3), 3.92 (s, 3 H, OCH3),
6.68 (d, 3J = 8.2 Hz, 1 Harom), 7.60 (d, 3J = 8.2 Hz, 1 Harom), 11.08 (s,
1 H, OH).
HRMS (EI): m/z calcd for C10H11ClO3 (M+): 214.0391; found:
214.0391.
13C NMR (250 MHz, CDCl3): d = 10.8 (CH3), 14.0 (CH2CH3), 23.1
(CH2CH2CH3), 36.1 (CH2CH2CH3), 52.0 (OCH3), 109.3 (Carom),
119.9 (CHarom), 124.2 (Carom), 126.4 (CHarom), 149.2, 159.9 (Carom),
171.1 (C=O).
MS (EI, 70 eV): m/z (%) = 208 (M+, 44), 177 (20), 176 (79), 161
(100), 148 (46), 119 (20).
Anal. Calcd for C10H11ClO3: C, 55.96; H, 5.17. Found: C, 55.79; H,
5.40.
3-Hexyl-2-hydroxy-6-methylbenzoic Acid Methyl Ester (13f)
Starting from 4-methoxybut-3-en-2-one (11a; 0.100 g, 1.0 mmol)
and 1-ethoxy-1,3-bis(trimethylsilyloxy)deca-1,3-diene (4i; 0.344 g,
1.0 mmol) in CH2Cl2 (5 mL), 13f was isolated as a yellow oil
(0.138 g, 55%).
HRMS (EI): m/z calcd for C12H16O3 (M+): 208.1094; found:
208.1093.
IR (neat): 3094 (w), 3034 (w), 2955 (s), 2929 (s), 2857 (s), 1751
(w), 1715 (w), 1660 (s), 1614 (m), 1582 (w), 1438 (s), 1417 (s),
1349 s), 1288 (s), 1256 (s), 1240 (s9, 1196 (m), 1146 (s), 1053 cm–1
(w).
1H NMR (300 MHz, CDCl3): d = 0.88 [t, 3J = 7.1 Hz, 3 H,
CH2(CH2)4CH3], 1.25–1.60 [m, 8 H, CH2(CH2)4CH3], 2.50 (s, 3 H,
CH3), 2.61 [t, 3J = 7.5 Hz, 2 H, CH2(CH2)4CH3], 3.96 (s, 3 H,
OCH3), 6.64 (d, 3J = 7.6 Hz, 1 Harom), 7.14 (d, 3J = 7.6 Hz, 1 Harom),
11.52 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 14.1, 22.6 (CH3), 23.8, 29.2,
29.3, 29.7, 31.7 (CH2), 51.9 (OCH3), 111.6 (Carom), 122.0 (CHarom),
128.8 (Carom), 134.2 (CHarom), 138.3, 160.7 (Carom), 172.6 (C=O).
MS (EI, 70 eV): m/z (%) = 250 (M+, 48), 190 (62), 161 (34), 148
(92), 147 (100), 120 (35).
2-Ethyl-6-hydroxybenzoic Acid Ethyl Ester (13i)
Starting from 1,1-dimethoxypentan-3-one (12a; 0.292 g, 2.0 mmol)
and 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (4l; 0.822 g,
3.0 mmol) in CH2Cl2 (5 mL), 13i was isolated as a mixture of regio-
isomers (rs = 6:1, 0.220 g, 56%). The spectroscopic data are listed
for the major isomer.
IR (neat): 3165 (w), 2968 (w), 2935 (w), 2874 (w), 1666 (s), 1621
(m), 1572 (m), 1500 (m), 1462 (m), 1398 (m), 1371 (m), 1330 (m),
1293 (m), 1255 (s), 1212 (s), 1172 (w), 1150 (s), 1093 (s), 1069 (m),
1058 (m), 1015 cm–1 (m).
1H NMR (300 MHz, CDCl3): d = 1.23 (t, 3J = 7.5 Hz, 3 H,
CH2CH3), 1.40 (t, 3J = 7.1 Hz, 3 H, OCH2CH3), 2.63 (q, 3J = 7.5 Hz,
2 H, CH2CH3), 4.38 (q, 3J = 7.1 Hz, 2 H, OCH2CH3), 6.69–6.1 (m,
2 Harom), 7.04 (d, 3J = 8.8 Hz, 1 Harom), 10.80 (s, 1 H, OH).
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

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Synthesis of Functionalized Salicylates
2247
13C NMR (250 MHz, CDCl3): d = 14.2 (OCH2CH3), 14.8
(CH2CH3), 29.0 (CH2CH3), 61.1 (OCH2CH3), 110.2 (Carom), 116.4,
119.1, 129.7 (CHarom), 151.5, 161.6 (Carom), 170.1 (C=O).
MS (EI, 70 eV): m/z (%) = 194 (M+, 34), 149 (22), 148 (100), 91
(25).
HRMS (EI): m/z calcd for C11H14O3 (M+): 194.0937; found:
194.0938.
1H NMR (300 MHz, CDCl3): d = 1.19 (t, 3J = 7.6 Hz, 3 H,
3
CH2CH3), 1.23 (t, J = 7.3 Hz, 3 H, CH2CH3), 2.20 (s, 3 H, CH3),
3
3
2.65 (q, J = 7.6 Hz, 2 H, CH2CH3), 3.00 (q, J = 7.3 Hz, 2 H,
3
3
CH2CH3), 6.71 (d, J = 8.2 Hz, 1 Harom), 7.55 (d, J = 8.2 Hz, 1
Harom), 12.79 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 8.4 (CH2CH3), 10.4 (CH3), 14.1
(CH2CH3), 27.1, 31.3 (CH2CH3), 116.5 (Carom), 118.6 (CHarom),
124.7 (Carom), 126.9 (CHarom), 151.3, 160.8 (Carom), 206.8 (C=O).
1-(2-Ethyl-6-hydroxyphenyl)ethanone (13j)
MS (EI, 70 eV): m/z (%) = 192 (M+, 19), 163 (100).
Starting from 1,1-dimethoxypentan-3-one (12a; 0.292 g, 2.0 mmol)
and 2,4-bis(trimethylsilyloxy)penta-1,3-diene (4m; 0.734 g,
3.0 mmol) in CH2Cl2 (5 mL), 13j was isolated as a mixture of regio-
isomers (rs = 4:1, 0.152 g, 46%). The spectroscopic data are listed
for the major isomer.
HRMS (EI): m/z calcd for C12H16O2 (M+): 192.1144; found:
192.1143.
2-Hydroxy-6-propylbenzoic Acid Ethyl Ester (13m)
Starting from 1,1-dimethoxyhexan-3-one (12b; 0.320 g, 2.0 mmol)
and 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (4l; 0.822 g,
3.0 mmol) in CH2Cl2 (5 mL), 13m was isolated as a mixture of re-
gioisomers (rs = 10:1, (0.134 g, 32%). The spectroscopic data are
listed for the major isomer.
IR (neat): 3033 (w), 2967 (w), 2932 (w), 2874 (w), 2726 (w), 1636
(s), 1621 (s), 1570 (m), 1502 (m), 1453 (w), 1421 (m), 1363 (s),
1323 (s), 1301 (m), 1274 (m), 1256 (s), 1221 (s), 1193 (m), 1164
(m), 1148 (m), 1136 (w), 1057 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 1.23 (t, 3J = 7.6 Hz, 3 H,
CH2CH3), 2.59 (s, 3 H, CH3), 2.63 (q, 3J = 7.6 Hz, 2 H, CH2CH3),
6.71–6.80 (m, 2 Harom), 6.63 (d, 3J = 8.1 Hz, 1 Harom), 12.29 (s, 1 H,
OH).
IR (neat): 3165 (w), 2960 (w), 2932 (w), 2872 (w), 1667 (s), 1622
(m), 1573(m), 1501 (w), 1464 (m), 1398 (w), 1371 (m), 1329 (m),
1303 (m), 1291 (m), 1277 (m), 1249 (s), 1208 (s), 1173 (w), 1150
(s), 1094 (s), 1015 cm–1 (w).
13C NMR (250 MHz, CDCl3): d = 14.6 (CH2CH3), 26.4 (CH3), 29.0
(CH2CH3), 117.1 (CHarom), 117.6 (Carom), 119.0, 130.6 (CHarom),
154.1, 162.5 (Carom), 203.8 (C=O).
MS (EI, 70 eV): m/z (%) = 164 (M+, 47), 149 (100).
HRMS (EI): m/z calcd for C10H12O2 (M+): 164.0831; found:
1H NMR (300 MHz, CDCl3): d = 0.93 (t, 3J = 7.3 Hz, 3 H,
CH2CH3), 1.40 (t, 3J = 7.1 Hz, 3 H, OCH2CH3), 1.65 (sext, 3J = 7.5
Hz, 2 H, CH2CH2CH3), 2.56 (t, 3J = 7.3 Hz, 2 H, CH2CH2CH3), 4.39
3
(q, J = 7.1 Hz, 2 H, OCH2CH3), 6.67–6.79 (m, 2 Harom), 7.74 (d,
3J = 8.1 Hz, 1 Harom), 10.79 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 13.7 (OCH2CH3), 14.1
(CH2CH3), 23.8 (CH2CH2CH3), 38.1 (CH2CH2CH3), 61.1
(OCH2CH3), 110.2 (Carom), 117.0, 119.7, 129.6 (CHarom), 151.5,
161.6 (Carom), 170.1 (C=O).
164.0833.
(2-Ethyl-6-hydroxyphenyl)phenylmethanone (13k)
Starting from 1,1-dimethoxypentan-3-one (12a; 0.292 g, 2.0 mmol)
and
[1,3-bis(trimethylsilyloxy)buta-1,3-dienyl]benzene
(4n;
MS (EI, 70 eV): m/z (%) = 208 (M+, 43), 163 (27), 162 (100), 134
0.919 g, 3.0 mmol) in CH2Cl2 (5 mL), 13k was isolated as a mixture
of regioisomers (rs = 4:1, 0.324 g, 72%). The spectroscopic data are
listed for the major isomer.
(92), 105 (34).
HRMS (EI): m/z calcd for C12H16O3 (M+): 208.1094; found:
208.1094.
IR (neat): 3057 (w), 3033 (w), 2966 (w), 2932 (w), 2873 (w), (1625
(s), 1598 (s), 1574 (s), 1497 (m), 1445 (m), 1414 (m), 1333 (s), 1299
(m), 1255 (s), 1225 (s), 1178 (m), 1160 (m), 1120 (m), 1096 (w),
1073 (w), 1027 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 1.26 (t, 3J = 7.6 Hz, 3 H,
CH2CH3), 2.67 (q, 3J = 7.6 Hz, 2 H, CH2CH3), 6.70 (d, 3J = 8.2 Hz,
1 Harom), 6.89 (d, 3J = 8.8 Hz, 1 Harom), 7.48–7.68 (m, 6 Harom), 12.14
(s, 1 H, OH).
2-Hydroxy-3-methoxy-6-propylbenzoic Acid Methyl Ester
(13n)
Starting from 1,1-dimethoxyhexan-3-one (12b; 0.320 g, 2.0 mmol)
and 1,4-dimethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (4g;
0.870 g, 3.0 mmol) in CH2Cl2 (5 mL), 13n was isolated as a mixture
of regioisomers (rs = 8:1, 0.167 g, 28%). The spectroscopic data are
listed for the major isomer.
IR (neat): 3152 (w), 2957 (m), 2933 (w), 2871 (w), 1672 (s), 1616
(w), 1573 (w), 1498 (w), 1438 (s), 1414 (m), 1322 (s), 1292 (m),
1322 (s), 1292 (m), 1253 (s), 1199 (s), 1153 (m), 1093 (w), 1068
(w), 1045 (m), 1034 (m), 1010 cm–1 (w).
1H NMR (300 MHz, CDCl3): d = 0.95 (t, 3J = 7.3 Hz, 3 H,
CH2CH3), 1.62 (sext, 3J = 7.5 Hz, 2 H, CH2CH2CH3), 2.63 (t,
3J = 7.5 Hz, 2 H, CH2CH2CH3), 3.88 (s, 3 H, OCH3), 3.92 (s, 3 H,
OCH3), 6.68 (d, 3J = 8.3 Hz, 1 Harom), 7.49 (d, 3J = 8.2 Hz, 1 Harom),
10.89 (s, 1 H, OH).
13C NMR (250 MHz, CDCl3): d = 14.0 (CH2CH3), 23.4
(CH2CH2CH3), 32.7 (CH2CH2CH3), 52.1, 60.4 (OCH3), 111.3
(Carom), 119.8, 124.1 (CHarom), 143.2, 146.2, 155.1 (Carom), 170.7
(C=O).
13C NMR (250 MHz, CDCl3): d = 14.6 (CH2CH3), 29.1 (CH2CH3),
117.0 (Carom), 117.2, 118.7, 128.2, 129.0, 131.6, 133.5, 138.1
(CHarom), 154.1, 163.5 (Carom), 201.0 (C=O).
MS (EI, 70 eV): m/z (%) = 226 (M+, 82), 225 (100), 149 (46).
HRMS (EI): m/z calcd for C15H14O2 (M+): 226.0910; found:
226.0909.
1-(6-Ethyl-2-hydroxy-3-methylphenyl)propan-1-one (13l)
Starting from 1,1-dimethoxypentan-3-one (12a; 0.292 g, 2.0 mmol)
and 3,5-bis(trimethylsilyloxy)hepta-2,4-diene (4k; 0.816 g,
3.0 mmol) in CH2Cl2 (5 mL), 13l was isolated as a mixture of regio-
isomers (rs = 4:1, 0.130 g, 34%). The spectroscopic data are listed
for the major isomer.
MS (EI, 70 eV): m/z (%) = 224 (M+, 46), 193 (20), 192 (100), 177
(75), 164 (40), 163 (16).
HRMS (EI): m/z calcd for C12H16O4 (M+): 224.1043; found:
224.1039.
IR (neat): 2968 (w), 2938 (w), 2876 (w), 1629 (s), 1574 /w), 1495
(w), 1454 (w), 1410 (m), 1373 (m), 1298 (m), 1275 (m), 1258 (m),
1230 (s), 1211 (m), 1140 (w), 1096 (m), 1051 (m), 1035 (m), 1009
cm–1 (m).
Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York

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G. Mroß et al.
PAPER
(4) (a) Kamisuki, S.; Takahashi, S.; Mizushina, Y.; Hanashima,
S.; Kuramochi, K.; Kobayashi, S.; Sakaguchi, K.; Nakata,
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R.; Tomoda, H.; Dong, Y.; Omura, S. J. Antibiot. 1999, 52,
572. (c) Khan, K. A.; Shoeb, A. Phytochemistry 1984, 23,
765.
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Acknowledgment
Financial support by the State of Mecklenburg-Vorpommern is
gratefully acknowledged.
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Synthesis 2009, No. 13, 2236–2248 © Thieme Stuttgart · New York