A straightforward methodology for the introduction of aryl and vinyl substituents in the 5 or 7 position of 8-hydroxyquinoline

Article abstract of DOI:10.1055/s-2006-926397

A straightforward and general procedure for the introduction of aryl and vinyl substituents in the 5 or 7 position of 8-hydroxyquinoline has been developed. The methodology presented is based upon the Suzuki cross-coupling reaction of aryl or vinyl halide

Full text of DOI:10.1055/s-2006-926397

PAPER
1325
A Straightforward Methodology for the Introduction of Aryl and Vinyl
Substituents in the 5 or 7 Position of 8-Hydroxyquinoline
Synthesis of
5
r
and 7-S
a
ubstituted 8
n
-Hydroxyqu
c
inolines esco Babudri,*a,b Antonio Cardone,a Carla T. Cioffi,b Gianluca M. Farinola,b Francesco Naso,a,b Roberta Ragnib
a
CNR Istituto di Chimica dei Composti OrganoMetallici, via Orabona 4, 70126 Bari, Italy
Dipartimento di Chimica, Università degli Studi di Bari, via Orabona 4, 70126 Bari, Italy
Fax +39(080)5442924; E-mail: babudri@chimica.uniba.it
b
Received 5 October 2005; revised 22 November 2005
these considerations, the development of a general route
to 5- or 7-functionalized 8-hydroxyquinolines appears
particularly desirable.
Abstract: A straightforward and general procedure for the intro-
duction of aryl and vinyl substituents in the 5 or 7 position of 8-hy-
droxyquinoline has been developed. The methodology presented is
based upon the Suzuki cross-coupling reaction of aryl or vinyl ha-
lides with 5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)quinolin-
8-ol or 7-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)quinolin-8-
ol, respectively, that have been obtained regioselectively starting
from 8-hydroxyquinoline.
Several synthetic approaches to substituted 8-hydroxy-
quinolines have been worked out thus far. The use of con-
ventional methodologies based on the construction of the
8-hydroxyquinoline skeleton via modified Skraup con-
densation is mainly restricted to the preparation of deriv-
atives functionalized on the pyridine ring.5,13 Mannich-
type condensation reactions of 8-hydroxyquinoline and
formaldehyde have been used to introduce functional
groups in the C-7 position.5,14 Some C-5-functionalized
derivatives have been obtained by electrophilic aromatic
substitution reactions.15 A higher level of versatility is
provided by synthetic protocols involving organometallic
reagents. A series of 8-hydroxyquinolines substituted at
the C-7 position have been obtained by metal–halogen ex-
change reaction of 7-bromo-8-methoxyquinoline with
phenyllithium and subsequent quenching of the resulting
metalated derivative with various electrophiles.16 Suzuki–
Miyaura cross-coupling of aromatic boronic acids17 or
Cassar–Heck–Sonogashira18 coupling of terminal alkynes
with 5-halo-8-tert-butoxycarbonyloxy- or 5-halo-8-ben-
zyloxyquinoline allowed access, after deprotection of the
hydroxyl group, to the corresponding 8-hydroxyquino-
lines bearing, at the C-5 position, aryl or arylethynyl
groups substituted with electron-withdrawing or electron-
donating functionalities. On the other hand, the synthesis
of similar 7-substituted 8-hydroxyquinolines starting
from the suitable halogen derivative using these versatile
coupling reactions has not been exploited.
Key words: hydroxyquinolines, cross-coupling, boron derivatives,
halogenation, regioselectivity
8-Hydroxyquinoline derivatives have found a great vari-
ety of applications as insecticides,1 antibacterial,2 fungi-
cidal,3 neuroprotective,4 anti-HIV agents5 or b-adrenergic
agonists.6 Moreover, owing to their chelating ability to-
ward a great number of metal cations,7 some of these het-
erocyclic derivatives have been employed as metal
sequestering agents in agriculture,8 as active materials for
specific fluorescent chemosensors9 or as building blocks
in supramolecular architectures.10 Among the various
metal chelates derivable from ligands with 8-quinolinol
structure, (8-hydroxyquinolinato)aluminium(III) (AlQ3)
has attracted a special interest as electroluminescent and
electron-transporting material for the fabrication of stable
and durable organic light emitting devices (OLEDs).11 In
particular, the possibility of tuning the emission wave-
length of these complexes by changing the chelated metal
cation or by modifying the structure of the chelating
ligands is an attractive feature for their use in the fabrica-
tion of full color screens based upon the OLED technolo-
gy.12 Indeed, photophysical studies have shown that light
emission of AlQ3-type complexes originates from elec-
tronic p-p* transitions centered on quinolate ligands, in
which the HOMO and LUMO orbitals are localized on the
phenoxide and on the pyridyl rings, respectively. There-
fore, the relative energy of these orbitals, and the emission
color, is affected by the functionalization of the ligands. In
particular, it has been predicted that electron-donating
substituents in the C-5 or C-7 positions of the quinoline
skeleton cause a red-shift of the complex emission, while
a blue-shift is expected when electron-withdrawing
groups are attached in the same positions.12 In light of
In the frame of our studies dealing with the development
of organometallic approaches to molecular and polymeric
organic materials for electrical and electro-optical appli-
cations,19 we report herein a new straightforward and
general route to both 5- and 7-substituted-8-hydroxy-
quinolines based upon the Suzuki–Miyaura coupling re-
action of boronic derivatives of 8-hydroxyquinoline with
aryl and vinyl halides. Our approach to the functionaliza-
tion in the C-5 or C-7 position is outlined in Scheme 1.
This synthetic pathway, unlike the previously reported
routes based upon the Suzuki–Miyaura methodology,17
involves the coupling reaction of the heterocyclic boronic
esters 5 and 6 with aromatic or vinyl halides which are, in
general, more easily available than the corresponding bo-
ron derivatives and allow a wider choice regarding the
SYNTHESIS 2006, No. 8, pp 1325–1332
x
x
.
x
x
.2
0
0
6
Advanced online publication: 27.03.2006
DOI: 10.1055/s-2006-926397; Art ID: T14005SS
© Georg Thieme Verlag Stuttgart · New York

1326
F. Babudri et al.
PAPER
OH
N
OH
OTBDMS
N
OTBDMS
OH
(ii)
(i)
I
N
I
N
N
(iii)
(iii)
I
I
(66%)
(76%)
4
2
1 (85%)
(60%)
3
(iv)
(iv)
OTBDMS
N
OTBDMS
N
OTBDMS
N
O
OTBDMS
N
Ar
B
(v)
O
(v)
B
Ar
O
O
(60%)
6
8a–e
(90–98%)
9a–e
(95–98%)
(vi)
(vi)
(85%)
5
OH
OH
N
Ar
N
Ar
,
10a–e
(75–98%)
(75–98%)
11a–e
,
,
,
NO2
Ar =
NO2
S
S
N
Scheme 1 Reagents and conditions: (i) NaI, NaOH, 5% NaOCl, MeOH, –30 °C; (ii) NIS, CHCl3, 40 °C; (iii) imidazole, TBDMSCl, CH2Cl2,
r.t.; (iv) pinacolborane, Et3N, PdCl2(dppf), 1,4-dioxane, 80 °C; (v) ArX (7a–e), 2 M Na2CO3, Pd(PPh3)4, toluene, EtOH, 80 °C; (vi) 2 M NaOH,
MeOH, r.t.
functionalities that can be introduced on the heterocyclic boronic esters 5 and 6 with a series of aryl halides 7a–d or
system. Some 5-substituted 8-hydroxyquinolines have re- the vinyl halide 7e, in the presence of aqueous Na2CO3
cently been obtained following a similar strategy17b that, and Pd(PPh3)4, using a mixture of toluene and ethanol as
however, has not been extended to the preparation of 7- the solvent, afforded the protected 8-hydroxyquinolines
substituted derivatives. The key step of our procedure is 8a–e and 9a–e in high yields. The desilylation reaction of
represented by the regioselective halogenation reaction, 8a–e and 9a–e with NaOH in methanol24 successfully led
which occurs in the C-5 or C-7 position (Scheme 1, steps to the final products 10a–e and 11a–e in good to excellent
i and ii) depending on the experimental conditions. Actu- yields (Table 1). It is worth noting that the choice of the
ally, the 5-iodo derivative 1 can be obtained by a simple protection of hydroxyl groups of 1 and 2 as tert-butyl-
iodination of 8-hydroxyquinoline with NaI and NaOCl at dimethylsilyl ethers enabled the introduction of function-
–30 °C.20 Although the methods reported in the literature alities, as in the case of the styryl derivatives 8e and 9e,
for the preparation of the 7-iodo derivative 2 appear more which are otherwise not compatible with the deprotection
complex,21 we have obtained this intermediate as a single conditions of the alternative benzyl or tert-butoxycarbon-
product in 66% yield by an easy iodination reaction with yl protecting groups.
N-iodosuccinimide in chloroform at 40 °C. The iodo de-
In conclusion, the methodology presented in this work al-
rivatives 1 and 2 have been characterized and unambigu-
lows a straightforward regioselective functionalization of
1
ously identified by comparing their H NMR and 13C
8-hydroxyquinoline in the C-5 or C-7 position, involving
NMR spectra with those already reported in the literature
operatively simple synthetic steps which occur in high
yields. The pinacol boronates 5 and 6, which represent the
key intermediates of this synthetic strategy, can be ob-
for the same products. In particular, the values of 13C
NMR chemical shifts of the iodine bearing carbon atoms
are crucial for the assignment of the structure [13C NMR:
tained in good yield by the palladium-catalyzed coupling
5-iodo derivative, d = 83.3 (C-5); 7-iodo derivative
reaction of the iodo derivatives 3 and 4 with pinacolbo-
d = 78.9 (C-7)].22 Both the iodoquinolinols are converted,
rane. 5-Iodo-8-hydroxyquinoline (1) and 7-iodo-8-hy-
by a standard procedure, to the corresponding tert-bu-
droxyquinoline (2) have been prepared by regioselective
tyldimethylsilyl ethers (Scheme 1, step iii) 3 and 4, which
halogenation reactions; in particular, the reaction of N-
gave the boronic esters 5 and 6, respectively, in high
iodosuccinimide with 8-hydroxyquinoline, at variance
yields by palladium-catalyzed coupling with pinacolbo-
rane.23 The Suzuki–Miyaura cross-coupling reactions of
Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York

PAPER
Synthesis of 5- and 7-Substituted 8-Hydroxyquinolines
1327
Table 1 Coupling Reactions of 5 (6) with Halides 7a–e and Desilylation to 8-Quinolinols 10a–e (11a–e)
ArX
Aryl Halide
Yield of 8 (%)
Yield of 9 (%)
Yield of 10 (%)
Yield of 11 (%)
7a
98
98
98
98
90
98
75
I
7b
7c
7d
90
96
98
98
98
95
90
93
75
S
Br
S
O2N
Br
O2N
Br
N
7e
98
96
98
90
Br
with the literature report,21a afforded in our hands the 7-
iodo-8-quinolinol as the single regioisomer.
stirred for 20 h at 40 °C. Then, the resulting suspension was filtered
and the organic phase was washed with a 5% aq Na2S2O3 solution
(2 × 50 mL) and dried (Na2SO4). After the distillation of the solvent
at reduced pressure, the product was isolated as a light-yellow solid
by crystallization from MeOH–H2O (6.15 g, 66%); mp 133–134 °C.
All chemicals were purchased from Aldrich and used without fur-
ther purification. Toluene and 1,4-dioxane were freshly distilled
from sodium and benzophenone under N2, immediately prior to use.
CH2Cl2 was distilled from P2O5 under N2. Dichloro[1,1¢-bis(diphe-
nylphosphino)ferrocene]palladium(II) [PdCl2(dppf)] was prepared
according to the literature.25 Petroleum ether used refers to the frac-
tion boiling in the range 40–60 °C. Column chromatography was
performed using silica gel 60, 40–63 mm from Merck. Merck silica
gel 60 F254 aluminum sheets were used for analytical TLC. FT-IR
spectra were measured on a Perkin-Elmer 1710 spectrophotometer
as dry KBr pellets. 1H and 13C NMR spectra were recorded in CDCl3
or DMSO-d6 on a Bruker AM 500 spectrometer at 500 MHz and
125 MHz, respectively. The residual CHCl3 or DMSO signal at
d = 7.24 (or 2.49) and the CDCl3 (or DMSO-d6) signal at d = 77.0
FT-IR (KBr): 3309, 1572, 1487, 1465, 1392, 1379, 1328, 1276,
1196, 1113 cm–1.
1H NMR, 13C NMR spectra are consistent with the data already re-
ported in the literature for the product 2.21
MS (EI, 70 eV): m/z (%) = 271 (M+, 100), 243 (10), 144 (13), 116
(71), 115 (12), 89 (53), 88 (12).
8-(tert-Butyldimethylsilyloxy)-5-iodoquinoline (3)
8-Hydroxy-5-iodoquinoline (1; 7.0 g, 25.8 mmol), imidazole (1.85
g, 27.2 mmol) and tert-butyldimethylsilyl chloride (4.28 g, 28.4
mmol) were dissolved in anhyd CH2Cl2 (40 mL) under N2. After
stirring vigorously overnight, the mixture was diluted with CH2Cl2
(60 mL) and washed successively with 5% aq HCl (2 × 30 mL) and
H2O (40 mL). The organic layer was dried (Na2SO4) and the solvent
distilled under reduced pressure to yield a dense brown liquid. The
final product was isolated as a light-yellow solid by distillation at
125 °C/6 × 10–5 mbar (5.96 g, 60%); mp 35–36 °C.
1
(or 39.5) were used as the standards for H NMR and 13C NMR
spectra, respectively. MS spectra were recorded on a Shimadzu
GCMS-QP 5000 spectrometer. Elemental analyses were done by a
Carlo Erba CHNS-O EA1108-Elemental Analyzer. A Büchi GKR-
51 apparatus was used to purify the products 3, 4, 5 and 6 by distil-
lation.
FT-IR (KBr): 2955, 2925, 2854, 1585, 1490, 1459, 1382, 1313,
1251, 1076, 851, 833, 783 cm–1.
8-Hydroxy-5-iodoquinoline (1)
8-Hydroxyquinoline (5.0 g, 34.4 mmol), NaI (5.16 g, 34.4 mmol)
and NaOH (1.38 g, 34.4 mmol) were dissolved in MeOH (150 mL)
and the resulting solution was degassed by bubbling N2 for 30 min
at r.t. After cooling the system to –30 °C, a 5% aq NaOCl solution
(49 mL) was added dropwise. The mixture was vigorously stirred at
–30 °C for 30 min and then neutralized with a 10% aq HCl solution.
The product, precipitated from solution, was collected by filtration.
After several recrystallizations from MeOH–H2O, a light-yellow
solid was obtained (7.92 g, 85%); mp 84–85 °C.
1H NMR (500 MHz, CDCl3): d = 8.82 (dd, J = 1.6, 3.9 Hz, 1 H, H-
2), 8.30 (dd, J = 1.6, 8.2 Hz, 1 H, H-4), 7.95 (d, J = 8.3 Hz, 1 H, H-
6), 7.44 (dd, J = 3.9, 8.2 Hz, 1 H, H-3), 6.97 (d, J = 8.3 Hz, 1 H, H-
7), 1.08 [s, 9 H, C(CH3)3], 0.38 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 154.0, 149.1, 142.9, 140.0, 137.7,
130.9, 122.8, 119.3, 87.2, 25.9, 18.8, –3.9.
MS (EI, 70 eV): m/z (%) = 370 ([M+ – CH3], 2), 329 (17), 328 (100),
202 (9), 201 (37), 186 (8), 172 (7), 142 (9), 73 (7), 45 (7), 43 (10).
Anal. Calcd for C15H20INOSi: C, 46.76; H, 5.23; N, 3.64. Found: C,
46.96; H, 5.14; N, 3.61.
FT-IR (KBr): 3327, 1588, 1500, 1461, 1408, 1349, 1278, 1202
cm–1.
1H NMR and 13C NMR spectra are consistent with the correspond-
8-(tert-Butyldimethylsilyloxy)-7-iodoquinoline (4)
ing data of 1 already reported in the literature.21
The product 4 was prepared via the same protocol described for the
synthesis of 3, using 8-hydroxy-7-iodoquinoline (2) as the starting
material. In this case, the distillation (125 °C, 6 × 10–5 mbar) yield-
ed 7.55 g (76%) of pure 4 as a light-yellow solid; mp 56–57 °C.
MS (EI, 70 eV): m/z (%) = 271 (M+, 100), 144 (15), 116 (53), 89
(41), 63 (30), 62 (20), 58 (19), 50 (12).
8-Hydroxy-7-iodoquinoline (2)
A solution of 8-hydroxyquinoline (5.0 g, 34.4 mmol) and N-iodo-
succinimide (9.3 g, 41.3 mmol) in CHCl3 (150 mL) was vigorously
FT-IR (KBr): 2957, 2929, 2881, 2852, 1558, 1486, 1456, 1383,
1255, 1242, 1099, 915, 834, 783 cm–1.
Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York

1328
F. Babudri et al.
PAPER
1H NMR (500 MHz, CDCl3): d = 8.77 (dd, J = 1.6, 4.4 Hz, 1 H, H-
2), 8.07 (dd, J = 1.6, 8.3 Hz, 1 H, H-4), 7.85 (d, J = 8.7 Hz, 1 H, H-
6), 7.38 (dd, J = 4.4, 8.3 Hz, 1 H, H-3), 7.11 (d, J = 8.7 Hz, 1 H, H-
5), 1.17 [s, 9 H, C(CH3)3], 0.40 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 153.7, 147.2, 139.9, 136.6, 135.6,
129.2, 121.5, 120.3, 86.9, 26.4, 19.6, –2.06.
Na2CO3 solution (65 mL) was degassed by bubbling N2 for 30 min.
Then Pd(PPh3)4 (0.36 g, 0.3 mmol) was added and the mixture was
stirred for 4 h at 80 °C. After cooling to r.t., the mixture was diluted
with H2O (100 mL) and extracted with Et2O (3 × 50 mL). The com-
bined organic layers were dried (Na2SO4) and the solvent removed
under reduced pressure. The crude product 8 (9) was purified by
flash chromatography over silica gel and crystallization.
MS (EI, 70 eV): m/z (%) = 370 ([M+ – CH3], 2), 329 (18), 328 (100),
202 (8), 201 (34), 186 (7), 142 (7), 73 (7), 43 (7).
8-(tert-Butyldimethylsilyloxy)-5-phenylquinoline (8a)
Eluent for chromatography: PE–CH2Cl2 (1:1); yield: 1.71 g (98%);
white solid; mp 49–50 °C (MeOH–H2O).
Anal. Calcd for C15H20INOSi: C, 46.76; H, 5.23; N, 3.64. Found: C,
46.51; H, 5.39; N, 3.62.
FT-IR (KBr): 2953, 2925, 2854, 1574, 1505, 1469, 1399, 1317,
1246, 1105, 1078, 861, 841, 784 cm–1.
8-(tert-Butyldimethylsilyloxy)-5-(4,4,5,5-tetramethyl[1,3,2]di-
oxaborolan-2-yl)quinoline (5)
1H NMR (500 MHz, CDCl3): d = 8.87 (dd, J = 1.5, 4.0 Hz, 1 H, H-
2), 8.21 (dd, J = 1.5, 8.3 Hz, 1 H, H-4), 7.51–7.40 (m, 5 H, C6H5),
7.39 (d, J = 7.8 Hz, 1 H, H-6), 7.32 (dd, J = 4.0, 8.3 Hz, 1 H, H-3),
7.24 (d, J = 7.8 Hz, 1 H, H-7), 1.10 [s, 9 H, C(CH3)3], 0.33 (s, 6 H,
2 CH3).
13C NMR (125 MHz, CDCl3): d = 152.3, 148.2, 142.0, 139.7, 134.0,
132.9, 130.2, 128.4, 127.6, 127.1, 121.0, 117.2, 26.0, 18.9, –3.8.
5-Iodo-8-tert-butyldimethylsilyloxyquinoline (3; 9.5 g, 24.7
mmol), pinacolborane (5.4 mL, 37.2 mmol), Et3N (10.3 mL, 70
mmol) and PdCl2(dppf) (0.54 g, 0.7 mmol) were dissolved in anhyd
1,4-dioxane (80 mL) under N2 and the solution was stirred over-
night at 80 °C. After cooling to r.t., the mixture was poured into ice-
water (80 mL) and extracted with hexane (3 × 70 mL). The com-
bined organic layers were dried (Na2SO4) and the distillation of the
solvent under reduced pressure afforded a crude brown liquid. Puri-
fication by distillation (140 °C, 6 × 10–5 mbar) afforded 8.09 g
(85%) of final product as a pale-yellow solid; mp 78–79 °C.
MS (EI, 70 eV): m/z (%) = 320 ([M+ – CH3], 2), 279 (23), 278 (100),
248 (13), 139 (15).
Anal. Calcd for C21H25NOSi: C, 75.18; H, 7.51; N, 4.17. Found: C,
75.29; H, 7.37; N, 3.97.
FT-IR (KBr): 2977, 2954, 2928, 2855, 1601, 1570, 1503, 1481,
1372, 1335, 1323, 1297, 1249, 1147, 1081, 876 cm–1.
1H NMR (500 MHz, CDCl3): d = 9.08 (dd, J = 1.6, 8.3 Hz, 1 H, H-
2), 8.84 (dd, J = 1.6, 4.0 Hz, 1 H, H-4), 8.04 (d, J = 7.5 Hz, 1 H, H-
6), 7.41 (dd, J = 4.0, 8.3 Hz, 1 H, H-3), 7.17 (d, J = 7.5 Hz, 1 H, H-
7), 1.40 (s, 12 H, 4 CH3), 1.07 [s, 9 H, C(CH3)3], 0.28 (s, 6 H, 2
CH3).
13C NMR (125 MHz, CDCl3): d = 156.0, 148.0, 142.0, 137.3, 136.5,
133.7, 121.5, 117.2, 83.6, 25.9, 24.9, 18.9, –3.9.
8-(tert-Butyldimethylsilyloxy)-5-thiophen-2-ylquinoline (8b)
Eluent for chromatography: PE–CH2Cl2 (1:1); yield: 1.60 g (90%);
white solid; mp 68–69 °C (MeOH–H2O).
FT-IR (KBr): 2951, 2924, 2853, 1591, 1572, 1500, 1469, 1396,
1300, 1270, 1244, 1093, 1077, 858, 828, 790 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.88 (dd, J = 1.6, 4.0 Hz, 1 H, H-
2), 8.48 (dd, J = 1.6, 8.4 Hz, 1 H, H-4), 7.52 (d, J = 7.9 Hz, 1 H, H-
6), 7.41 (dd, J = 1.2, 4.8 Hz, 1 H, thiophene H-5), 7.38 (dd, J = 4.0,
8.4 Hz, 1 H, H-3), 7.20 (d, J = 7.9 Hz, 1 H, H-7), 7.18 – 7.16 (m, 2
H, thiophene H-3, H-4), 1.10 [s, 9 H, C(CH3)3], 0.32 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 153.0, 148.4, 142.0, 140.9, 133.9,
128.9, 128.2, 127.3, 127.1, 125.5, 125.0, 121.4, 117.2, 26.0, 18.9, –
3.9.
MS (EI, 70 eV): m/z (%) = 370 ([M+ – CH3], 3), 329 (26), 328 (100),
327 (25), 228 (46), 227 (12), 198 (15), 43 (12).
Anal. Calcd for C21H32BNO3Si: C, 65.45; H, 8.37; N, 3.63. Found:
C, 65.66; H, 8.59; N, 3.70.
8-(tert-Butyldimethylsilyloxy)-7-(4,4,5,5-tetramethyl[1,3,2]di-
oxaborolan-2-yl)quinoline (6)
This compound was obtained using the same experimental proce-
dure described for the synthesis of 5, starting from the aryl halide 4
(9.5 g, 24.7 mmol). The product 6 was isolated as a pale-yellow sol-
id by distillation at 130 °C/6 × 10–5 mbar (5.71 g, 60%); mp 80–
81 °C.
MS (EI, 70 eV): m/z (%) = 326 ([M+ – CH3], 2), 286 (10), 285 (21),
284 (100), 254 (13), 142 (8).
Anal. Calcd for C19H23NOSSi: C, 66.82; H, 6.79; N, 4.10; S, 9.39.
Found: C, 66.64; H, 6.78; N, 4.10; S, 9.47.
8-(tert-Butyldimethylsilyloxy)-5-(5-nitrothiophen-2-yl)-
quinoline (8c)
Eluent for chromatography: PE–acetone (9:1); yield: 1.93 g (96%);
FT-IR (KBr): 2975, 2936, 2854, 1611, 1597, 1554, 1499, 1450,
1432, 1401, 1390, 1371, 1343, 1305, 1252, 1145, 1126, 1103, 834,
783 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.76 (dd, J = 1.6, 4.0 Hz, 1 H, H-
2), 8.06 (dd, J = 1.6, 8.3 Hz, 1 H, H-4), 7.80 (d, J = 8.2 Hz, 1 H, H-
6), 7.36 (dd, J = 4.0, 8.3 Hz, 1 H, H-3), 7.31 (d, J = 8.2 Hz, 1 H, H-
5), 1.38 (s, 12 H, 4 CH3), 1.10 [s, 9 H, C(CH3)3], 0.36 (s, 6 H, 2
CH3).
13C NMR (125 MHz, CDCl3): d = 159.4, 146.4, 140.7, 135.3, 133.3,
131.3, 121.9, 118.3, 83.5, 26.2, 25.0, 19.7, –2.1.
MS (EI, 70 eV): m/z (%) = 370 ([M+ – CH3], 3), 329 (26), 328 (100),
327 (27), 284 (16), 246 (21), 228 (47), 83 (43), 55 (33), 43 (17).
yellow solid; mp 120–121 °C (MeOH–H2O).
FT-IR (KBr): 2953, 2928, 2857, 1569, 1503, 1434, 1352, 1337,
1304, 1245, 1093, 836, 789 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.92 (dd, J = 1.9, 4.2 Hz, 1 H, H-
2), 8.43 (dd, J = 1.9, 8.6 Hz, 1 H, H-4), 7.99 (d, J = 4.0 Hz, 1 H,
thiophene H-4), 7.55 (d, J = 8.0 Hz, 1 H, H-6), 7.46 (dd, J = 4.2, 8.6
Hz, 1 H, H-3), 7.22 (d, J = 8.0 Hz, 1 H, H-7), 7.12 (d, J = 4.0 Hz, 1
H, thiophene H-3), 1.08 [s, 9 H, C(CH3)3], 0.32 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 154.8, 151.0, 149.3, 148.8, 142.0,
132.8, 129.7, 128.9, 127.5, 126.52, 122.3, 122.2, 117.2, 25.9, 18.9,
–3.8.
Anal. Calcd for C21H32BNO3Si: C, 65.45; H, 8.37; N, 3.63. Found:
C, 65.63; H, 8.68; N, 3.67.
MS (EI, 70 eV): m/z (%) = 371 ([M+ – CH3], 2), 330 (23), 329 (100),
283 (12), 226 (48), 196 (20), 73 (14).
Compounds 8a–e and 9a–e; General Procedure
A mixture of 5 (6) (5.2 mmol), aryl (7a–d) or vinyl (7e) halide (5.4
mmol), anhyd toluene (100 mL), EtOH (25 mL) and a 2 M aq
Anal. Calcd for C19H22N2O3SSi: C, 59.04; H, 5.74; N, 7.25; S, 8.30.
Found: C, 59.19; H, 5.93; N, 7.05; S, 8.58.
Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York

PAPER
Synthesis of 5- and 7-Substituted 8-Hydroxyquinolines
1329
8-(tert-Butyldimethylsilyloxy)-5-(5-nitropyridin-2-yl)quinoline
(8d)
FT-IR (KBr): 2951, 2923, 2852, 1494, 1453, 1375, 1245, 1102, 828,
787 cm–1.
Eluent for chromatography: PE–acetone (9:1); yield: 1.94 g (98%);
yellow solid; mp 144–145 °C (MeOH–H2O).
1H NMR (500 MHz, CDCl3): d = 8.83 (dd, J = 2.0, 4.0 Hz, 1 H, H-
2), 8.09 (dd, J = 2.0, 8.2 Hz, 1 H, H-4), 7.67 (d, J = 8.3 Hz, 1 H, H-
6), 7.50 (dd, J = 1.2, 3.6 Hz, 1 H, thiophene H-5), 7.41 (d, J = 8.3
Hz, 1 H, H-5), 7.38 (dd, J = 1.2, 5.2 Hz, 1 H, thiophene H-3), 7.36
(dd, J = 4.0, 8.2 Hz, 1 H, H-3), 7.13 (dd, J = 3.6, 5.2 Hz, 1 H,
thiophene H-4), 0.93 [s, 9 H, C(CH3)3], 0.22 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 149.5, 147.8, 141.8, 140.1, 135.4,
129.0, 128.7, 127.2, 126.9, 125.5, 123.4, 121.1, 119.6, 26.1, 19.2,
–2.5.
FT-IR (KBr): 2956, 2930, 2857, 1590, 1568, 1501, 1460, 1355,
1320, 1252, 849, 785 cm–1.
1H NMR (500 MHz, CDCl3): d = 9.58 (dd, J = 0.9, 2.8 Hz, 1 H, py-
ridine H-6), 8.91 (dd, J = 1.6, 4.0 Hz, 1 H, H-2), 8.65 (dd, J = 1.6,
8.7 Hz, 1 H, H-4), 8.60 (dd, J = 2.8, 8.6 Hz, 1 H, pyridine H-4), 7.78
(dd, J = 0.9, 8.6 Hz, 1 H, pyridine H-3), 7.68 (d, J = 8.0 Hz, 1 H, H-
6), 7.45 (dd, J = 4.0, 8.7 Hz, 1 H, H-3), 7.27 (d, J = 8.0 Hz, 1 H, H-
7), 1.08 [s, 9 H, C(CH3)3], 0.31 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 164.0, 155.2, 148.7, 144.8, 142.4,
142.1, 133.5, 131.8, 129.9, 128.4, 127.3, 124.4, 122.1, 117.2, 25.9,
18.9, –3.8.
MS (EI, 70 eV): m/z (%) = 326 ([M+ – CH3], 2), 286 (11), 285 (23),
284 (100), 254 (15), 142 (10).
Anal. Calcd for C19H23NOSSi: C, 66.82; H, 6.79; N, 4.10; S, 9.39.
Found: C, 66.92; H, 7.00; N, 4.13; S, 9.51.
MS (EI, 70 eV): m/z (%) = 366 ([M+ – CH3], 3), 325 (21), 324 (100),
278 (32), 277 (10), 201 (31), 73 (10).
8-(tert-Butyldimethylsilyloxy)-7-(5-nitrothiophen-2-yl)-
quinoline (9c)
Eluent for chromatography: PE–acetone (9:1); yield: 1.97 g (98%);
orange solid; mp 131–132 °C (hexane).
Anal. Calcd for C20H23 N3O3Si: C, 62.97; H, 6.08; N, 11.01. Found:
C, 62.96; H, 6.07; N, 10.89.
8-(tert-Butyldimethylsilyloxy)-5-styrylquinoline (8e)
Eluent for chromatography: PE–CH2Cl2 (1:1); yield: 1.84 g (98%);
yellow solid; mp 53–54 °C (MeOH–H2O).
FT-IR (KBr): 2949, 2926, 2855, 1494, 1455, 1343, 1324, 1251,
1104, 826, 798 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.85 (dd, J = 1.6, 4.0 Hz, 1 H, H-
2), 8.13 (dd, J = 1.6, 8.3 Hz, 1 H, H-4), 7.95 (d, J = 4.4 Hz, 1 H,
thiophene H-4), 7.68 (d, J = 8.5 Hz, 1 H, H-6), 7.45 (d, J = 8.5 Hz,
1 H, H-5), 7.45 (d, J = 4.4 Hz, 1 H, thiophene H-3), 7.44 (dd,
J = 4.0, 8.3 Hz, 1 H, H-3), 0.95 [s, 9 H, C(CH3)3], 0.33 (s, 6 H, 2
CH3).
13C NMR (125 MHz, CDCl3): d = 150.9, 148.1, 148.0, 141.2, 135.6,
129.8, 128.5, 128.4, 127.0, 125.5, 122.2, 120.4, 120.1, 26.4, 19.3,
–1.5.
FT-IR (KBr): 3028, 2950, 2927, 2853, 1572, 1503, 1471, 1405,
1327, 1310, 1279, 1244, 1167, 1089, 959, 829, 780 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.88 (dd, J = 1.6, 4.0 Hz, 1 H, H-
2), 8.50 (dd, J = 1.6, 8.7 Hz, 1 H, H-4), 7.72 (d, J = 16.0 Hz, 1 H,
vinylic H), 7.71 (d, J = 7.9 Hz, 1 H, H-6), 7.58 (d-like, J = ca. 8 Hz,
2 H, H-2, H-6 of C6H5), 7.42 (dd, J = 4.0, 8.7 Hz, 1 H, H-3), 7.40 (t-
like, J = ca. 8 Hz, 2 H, H-3, H-5 of C6H5), 7.30 (t-like, J = ca. 8 Hz,
1 H, H-4 of C6H5), 7.20 (d, J = 7.9 Hz, 1 H, H-7), 7.09 (d, J = 16.0
Hz, 1 H, vinylic H), 1.13 [s, 9 H, C(CH3)3], 0.34 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 152.8, 148.3, 141.9, 137.6, 131.8,
130.7, 128.7, 127.8, 127.6, 127.5, 126.5, 124.4, 124.3, 121.0, 117.8,
26.0, 18.9, –3.9.
MS (EI, 70 eV): m/z (%) = 371 ([M+ – CH3], 3), 330 (23), 329 (100),
283 (12), 226 (32), 196 (12).
Anal. Calcd for C19H22N2O3SSi: C, 59.04; H, 5.74; N, 7.25; S, 8.30.
Found: C, 58.98; H, 6.05; N, 7.25; S, 8.65.
MS (EI, 70 eV): m/z (%) = 346 ([M+ – CH3], 1), 305 (26), 304 (100),
302 (10), 152 (21), 145 (10).
8-(tert-Butyldimethylsilyloxy)-7-(5-nitropyridin-2-yl)quinoline
(9d)
Eluent for chromatography: PE–acetone (9:1); yield: 1.88 g (95%);
orange solid; mp 173–174 °C (hexane).
Anal. Calcd for C23H27NOSi: C, 76.41; H, 7.53; N, 3.87. Found: C,
76.37; H, 7.68; N, 3.60.
8-(tert-Butyldimethylsilyloxy)-7-phenylquinoline (9a)
Eluent for chromatography: PE–CH2Cl2 (1:1); yield: 1.71 g (98%);
white solid; mp 103–104 °C (MeOH–H2O).
FT-IR (KBr): 2949, 2925, 2852, 1591, 1570, 1513, 1469, 1446,
1346, 832, 787 cm–1.
1H NMR (500 MHz, CDCl3): d = 9.57 (dd, J = 0.8, 2.8 Hz, 1 H, py-
ridine H-6), 8.87 (dd, J = 1.6, 4.4 Hz, 1 H, H-2), 8.52 (dd, J = 2.8,
8.7 Hz, 1 H, pyridine H-4), 8.28 (dd, J = 0.8, 8.7 Hz, 1 H, pyridine
H-3), 8.16 (dd, J = 1.6, 8.3 Hz, 1 H, H-4), 7.95 (d, J = 8.4 Hz, 1 H,
H-6), 7.53 (d, J = 8.4 Hz, 1 H, H-5), 7.46 (dd, J = 4.4, 8.3 Hz, 1 H,
H-3), 0.85 [s, 9 H, C(CH3)3], 0.20 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 162.3, 151.6, 148.0, 145.0, 142.3,
141.6, 135.7, 130.5, 130.4, 128.4, 126.6, 126.3, 122.3, 120.2, 25.9,
19.1, –2.8.
FT-IR (KBr): 2952, 2926, 2852, 1490, 1460, 1440, 1390, 1365,
1248, 1109, 1084, 836, 752 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.85 (dd, J = 1.7, 4.3 Hz, 1 H, H-
2), 8.12 (dd, J = 1.7, 8.3 Hz, 1 H, H-4), 7.63 (dd, J = 1.2, 8.0 Hz, 2
H, H-2, H-6 of C6H5), 7.53 (d, J = 8.5 Hz, 1 H, H-6), 7.46 (d, J = 8.5
Hz, 1 H, H-5), 7.44 (t-like, J = ca. 8 Hz, 2 H, H-3, H-5 of C6H5),
7.38 (dd, J = 4.3, 8.3 Hz, 1 H, H-3), 7.35 (tt, J = 1.2, 8.0 Hz, 1 H, H-
4 of C6H5), 0.75 [s, 9 H, C(CH3)3], 0.12 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 149.6, 147.9, 141.9, 139.2, 135.5,
130.7, 130.2, 129.6, 128.7, 128.0, 126.9, 121.0, 119.6, 25.7, 18.9,
–3.3.
MS (EI, 70 eV): m/z (%) = 366 ([M+ – CH3], 3), 325 (24), 324 (100),
278 (23), 277 (11), 201 (11).
Anal. Calcd for C20H23N3O3Si: C, 62.97; H, 6.08; N, 11.01. Found:
C, 62.91; H, 5.83; N, 11.09.
MS (EI, 70 eV): m/z (%) = 320 ([M+ – CH3], 2), 279 (24), 278 (100),
248 (19), 139 (14).
8-(tert-Butyldimethylsilyloxy)-7-styrylquinoline (9e)
Eluent for chromatography: PE–CH2Cl2 (1:1); yield: 1.80 g (96%);
orange solid; mp 69–70 °C (MeOH–H2O).
Anal. Calcd for C21H25NOSi: C, 75.18; H, 7.51; N, 4.17. Found: C,
75.23; H, 7.34; N, 4.20.
8-(tert-Butyldimethylsilyloxy)-7-thiophen-2-ylquinoline (9b)
Eluent for chromatography: PE–CH2Cl2 (1:1); yield: 1.74 g (98%);
light-yellow solid; mp 107–108 °C (MeOH).
FT-IR (KBr): 3057, 2950, 2923, 2853, 1596, 1557, 1505, 1494,
1455, 1374, 1247, 1107, 969, 826, 786 cm–1.
Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York

1330
F. Babudri et al.
PAPER
1H NMR (500 MHz, CDCl3): d = 8.80 (dd, J = 1.6, 4.0 Hz, 1 H, H-
2), 8.06 (dd, J = 1.6, 8.2 Hz, 1 H, H-4), 7.96 (d, J = 16.6 Hz, 1 H,
vinylic H), 7.86 (d, J = 8.6 Hz, 1 H, H-6), 7.61 (d-like, J = ca. 8 Hz,
2 H, H-2, H-6 of C6H5), 7.41 (t-like, J = ca. 8 Hz, 2 H, H-3, H-5 of
C6H5), 7.39 (d, J = 8.6 Hz, 1 H, H-5), 7.33 (dd, J = 4.0, 8.2 Hz, 1 H,
H-3), 7.29 (t-like, J = ca. 8 Hz, 1 H, H-4 of C6H5), 7.14 (d, J = 16.6
Hz, 1 H, vinylic H), 1.17 [s, 9 H, C(CH3)3], 0.40 (s, 6 H, 2 CH3).
13C NMR (125 MHz, CDCl3): d = 150.0, 147.6, 141.5, 137.8, 135.4,
128.7, 127.5, 126.5, 125.6, 124.1, 123.9, 120.9, 119.5, 26.3, 19.5,
–2.7.
13C NMR (125 MHz, DMSO-d6): d = 155.4, 149.5, 149.1, 148.7,
138.4, 133.1, 130.5, 130.4, 127.5, 126.3, 123.1, 119.3, 111.1.
Anal. Calcd for C13H8N2O3S: C, 57.34; H, 2.96; N, 10.29; S, 11.78.
Found: C, 57.34; H, 3.06; N, 10.27; S, 11.81.
8-Hydroxy-5-(5-nitropyridin-2-yl)quinoline (10d)
Yield: 1.20 g (75%); yellow solid; mp 211–212 °C (MeOH–H2O).
FT-IR (KBr): 3386, 1598, 1572, 1504, 1351, 1266 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 10.44 (br s, 1 H, OH), 9.50 (d,
J = 2.6 Hz, 1 H, pyridine H-6), 8.93 (dd, J = 1.5, 4.0 Hz, 1 H, H-2),
8.81 (dd, J = 1.5, 8.7 Hz, 1 H, H-4), 8.69 (dd, J = 2.6, 8.7 Hz, 1H,
pyridine H-4), 8.00 (d, J = 8.7 Hz, 1 H, pyridine H-3), 7.83 (d,
J = 8.2 Hz, 1 H, H-6), 7.63 (dd, J = 4.0, 8.7 Hz, 1 H, H-3), 7.23 (d,
J = 8.2 Hz, 1H, H-7).
MS (EI, 70 eV): m/z (%) = 346 ([M+ – CH3], 2), 305 (25), 304 (100),
152 (15).
Anal. Calcd for C23H27NOSi: C, 76.41; H, 7.53; N, 3.87. Found: C,
76.71; H, 7.50; N, 3.77.
13C NMR (125 MHz, DMSO-d6): d = 162.9, 155.4, 148.4, 144.3,
Desilylation of 8a–e and 9a–e to 10a–e and 11a–e; General Pro-
cedure
A 2 M NaOH aq solution (60 mL, 120 mmol) was added dropwise
to a solution of 8 (9) (6.0 mmol) in MeOH (20 mL). After stirring
for 30 min, the mixture was neutralized with 5% aq HCl and the sol-
id product precipitated from solution. After filtration and washings
with H2O, the pure product was dried under vacuum.
142.2, 138.4, 134.2, 132.3, 130.8, 126.4, 125.7, 124.5, 122.6, 110.9.
Anal. Calcd for C14H9N3O3: C, 62.92; H, 3.39; N, 15.72. Found: C,
62.92; H, 3.21; N, 15.95.
8-Hydroxy-5-styrylquinoline (10e)
Yield: 1.45 g (98%); yellow solid; mp 210 °C (dec.) (MeOH–H2O).
FT-IR (KBr): 3436, 1573, 1506, 1457, 1401, 1268, 1089, 955 cm–1.
8-Hydroxy-5-(phenyl)quinoline (10a)
Yield: 1.30 g (98%); white solid; mp 95–96 °C (MeOH–H2O).
1H NMR (500 MHz, DMSO-d6): d = 9.98 (br s, 1 H, OH), 8.89 (d,
J = 3.8 Hz, 1H, H-2), 8.88 (d, J = 8.5 Hz, 1 H, H-4), 7.96 (d,
J = 16.0 Hz, 1H, vinylic H), 7.88 (d, J = 8.0 Hz, 1 H, H-6), 7.73 (d,
J = 7.5 Hz, 2 H, H-2, H-6 of C6H5), 7.62 (dd, J = 3.8, 8.5 Hz, 1 H,
H-3), 7.39 (t, J = 7.5 Hz, 2 H, H-3, H-5 of C6H5), 7.27 (t, J = 7.5 Hz,
1 H, H-4 of C6H5), 7.20 (d, J = 16.0 Hz, 1 H, vinylic H), 7.15 (d,
J = 8.0 Hz, 1 H, H-7).
13C NMR (125 MHz, DMSO-d6): d = 153.2, 147.9, 138.3, 137.4,
132.6, 128.9, 128.5, 127.3, 126.6, 126.5, 124.6, 124.3, 123.6, 121.7,
111.4.
FT-IR (KBr): 3316, 1579, 1513, 1472, 1415, 1366, 1283, 1266,
1238, 1198, 1182 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 8.77 (dd, J = 1.6, 4.0 Hz, 1 H,
H-2), 8.46 (br s, 1 H, OH), 8.24 (dd, J = 1.6, 8.7 Hz, 1 H, H-4),
7.48–7.39 (m, 5 H, C6H5), 7.41 (d, J = 8.0 Hz, 1 H, H-6), 7.37 (dd,
J = 4.0, 8.7 Hz, 1 H, H-3), 7.21 (d, J = 8.0 Hz, 1 H, H-7).
13C NMR (125 MHz, DMSO-d6): d = 151.6, 147.6, 139.4, 138.3,
134.7, 130.9, 130.1, 128.5, 128.2, 127.2, 126.7, 121.7, 109.5.
MS (EI, 70 eV): m/z (%) = 247 (M+, 100), 246 (50), 218 (24), 217
(26), 216 (11), 109 (31), 51 (12).
Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C,
81.53; H, 5.13; N, 6.10.
Anal. Calcd for C17H13NO: C, 82.57; H, 5.30; N, 5.66. Found: C,
82.69; H, 5.24; N, 5.85.
8-Hydroxy-5-(thiophen-2-yl)quinoline (10b)
Yield: 1.23 g (90%); orange solid; mp 207 °C (dec.) (MeOH–H2O).
FT-IR (KBr): 3371, 1577, 1503, 1471, 1411, 1277, 1186 cm–1.
8-Hydroxy-7-phenylquinoline (11a)
Yield: 1.30 g (98%); white solid; mp 150–151 °C (MeOH–H2O).
1H NMR (500 MHz, DMSO-d6): d = 10.09 (br s, 1 H, OH), 8.91 (dd,
J = 1.4, 4.1 Hz, 1 H, H-2), 8.49 (dd, J = 1.4, 8.7 Hz, 1 H, H-4), 7.66
(dd, J = 1.0, 5.0 Hz, 1 H, thiophene H-5), 7.61 (dd, J = 4.1, 8.7 Hz,
1 H, H-3), 7.54 (d, J = 8.0 Hz, 1 H, H-6), 7.25 (dd, J = 1.0, 3.7 Hz,
1 H, thiophene H-3), 7.22 (dd, J = 3.7, 5.0 Hz, 1 H, thiophene H-4),
7.15 (d, J = 8.0 Hz, 1 H, H-7).
13C NMR (125 MHz, DMSO-d6): d = 153.4, 148.2, 140.0, 138.4,
133.6, 129.2, 127.8, 127.1, 126.7, 126.1, 122.4, 121.8, 110.8.
MS (EI, 70 eV): m/z (%) = 227 (M+, 100), 199 (22), 82 (25), 80 (25),
77 (21), 63 (18), 51 (19), 45 (25).
FT-IR (KBr): 3321, 1492, 1466, 1404, 1376, 1284, 1195, 1105
cm–1.
1H NMR (500 MHz, DMSO-d6): d = 9.89 (s, 1 H, OH), 8.82 (dd,
J = 1.6, 4.4 Hz, 1 H, H-2), 8.20 (dd, J = 1.6, 8.3 Hz, 1H, H-4), 7.81
(d-like, J = ca. 8 Hz, 2 H, H-2, H-6 of C6H5), 7.64 (d, J = 8.8 Hz, 1
H, H-6), 7.50 (t-like, J = ca. 8 Hz, 2 H, H-3, H-5 of C6H5), 7.47 (dd,
J = 4.4, 8.3 Hz, 1 H, H-3), 7.43 (d, J = 8.8 Hz, 1 H, H-5), 7.38 (t-
like, J = ca. 8 Hz, 1 H, H-4 of C6H5).
13C NMR (125 MHz, DMSO-d6): d = 148.7, 148.0, 138.5, 137.6,
135.9, 129.4, 129.3, 128.3, 127.5, 127.2, 122.7, 121.6, 117.6.
MS (EI, 70 eV): m/z (%) = 221 (M+, 73), 220 (100), 191 (17), 110
(12), 96 (18), 84 (20), 82 (14), 43 (14).
Anal. Calcd for C13H9NOS: C, 68.70; H, 3.99; N, 6.16; S, 14.11.
Found: C, 68.67; H, 4.12; N, 6.09; S, 13.98.
8-Hydroxy-5-(5-nitrothiophen-2-yl)quinoline (10c)
Yield: 1.93 g (93%); orange solid; mp 210–211 °C (MeOH–H2O).
Anal. Calcd for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C,
81.33; H, 4.96; N, 6.25.
FT-IR (KBr): 3115, 1577, 1508, 1411, 1348, 1331, 1283, 1201
cm–1.
8-Hydroxy-7-(thiophen-2-yl)quinoline (11b)
Yield: 1.23 g (90%); yellow solid; mp 138–139 °C (MeOH–H2O).
1H NMR (500 MHz, DMSO-d6): d = 10.50 (br s, 1 H, OH), 8.95 (dd,
J = 1.4, 4.0 Hz, 1 H, H-2), 8.55 (dd, J = 1.4, 8.6 Hz, 1 H, H-4), 8.22
(d, J = 4.3 Hz, 1 H, thiophene H-4), 7.70 (d, J = 8.0 Hz, 1H, H-6),
7.67 (dd, J = 4.0, 8.6 Hz, 1H, H-3), 7.41 (d, J = 4.3, 1 H, thiophene
H-3), 7.18 (d, J = 8.0 Hz, 1 H, H-7).
FT-IR (KBr): 3265, 1497, 1465, 1407, 1383, 1327, 1263, 1197
cm–1.
1H NMR (500 MHz, DMSO-d6): d = 10.50 (br s, 1 H, OH), 8.80 (dd,
J = 1.4, 4.0 Hz, 1 H, H-2), 8.14 (dd, J = 1.4, 8.2 Hz, 1 H, H-4), 7.85
(d, J = 8.7 Hz, 1 H, H-6), 7.81 (d, J = 3.6 Hz, 1 H, thiophene H-5),
Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York

PAPER
Synthesis of 5- and 7-Substituted 8-Hydroxyquinolines
1331
7.42 (dd, J = 4.0, 8.2 Hz, 1 H, H-3), 7.41 (d, J = 5.1 Hz, 1 H,
thiophene H-3), 7.36 (d, J = 8.7 Hz, 1 H, H-5), 7.19 (dd, J = 3.6, 5.1
Hz, 1 H, thiophene H-4).
13C NMR (125 MHz, DMSO-d6): d = 148.5, 148.1, 139.0, 138.8,
136.0, 127.4, 126.9, 126.4, 126.2, 125.2, 121.7, 117.8, 116.4.
Acknowledgment
This work was financially supported by Ministero dell’Università e
della Ricerca Scientifica e Tecnologica, Rome (Project ‘Sintesi di
materiali organici per applicazioni ottiche’ L. 488 19/12/92, Piano
‘Materiali Innovativi’), and by the University of Bari.
MS (EI, 70 eV): m/z (%) = 227 (M+, 100), 226 (34), 198 (14), 154
(19), 92 (23), 77 (14), 45 (19), 44 (15), 43 (45).
References
Anal. Calcd for C13H9NOS: C, 68.70; H, 3.99; N, 6.16; S, 14.11.
Found: C, 68.60; H, 4.22; N, 6.12; S, 13.71.
(1) Crop Protection Chemical Index, 8th ed., FV 2; ICI Plant
Protection Div: Bracknell, 1977, 9.
8-Hydroxy-7-(5-nitrothiophen-2-yl)quinoline (11c)
Yield: 1.60 g (98%); brown solid; mp 290 °C (dec.) (MeOH–H2O).
(2) (a) Okide, G. B. J. Heterocycl. Chem. 2001, 38, 1213.
(b) Takayanagi, T.; Kudoh, T.; Yotsuyanagi, T. Chem. Lett.
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Cabantchik, Z. I.; Warshawsky, A.; Youdim, M. B. H.;
Fridkin, M. Bioorg. Med. Chem. 2005, 13, 773.
(5) Mekouar, K.; Mouscadet, J.-F.; Dismaële, D.; Subra, F.;
Leh, H.; Savouré, D.; Auclair, C.; d’Angelo, J. J. Med.
Chem. 1998, 41, 2846.
(6) Milecki, J.; Baker, S. P.; Standifer, K. M.; Ishizu, T.; Chida,
Y.; Kusiak, J. W.; Pitha, J. J. Med. Chem. 1987, 30, 1563.
(7) Lytle, F. E. Appl. Spectr. 1970, 24, 319.
(8) Baret, P.; Béguin, C. G.; Boukhalfa, H.; Caris, C.; Laulhère,
J.-P.; Pierre, J.-L.; Serratrice, G. J. Am. Chem. Soc. 1995,
117, 9760.
(9) (a) Jotterand, N.; Pearce, D. A.; Imperiali, B. J. Org. Chem.
2001, 66, 3224. (b) Walkup, G. K.; Imperiali, B. J. Org.
Chem. 1998, 63, 6727. (c) Bronson, R. T.; Bradshaw, J. S.;
Savage, P. B.; Fuangswasdi, S.; Lee, S. C.; Krakowiak, K.
E.; Izatt, R. M. J. Org. Chem. 2001, 66, 4752. (d) Moon, S.
Y.; Cha, N. R.; Kim, Y. H.; Chang, S. K. J. Org. Chem.
2004, 69, 181.
FT-IR (KBr): 3435, 1502, 1469, 1419, 1394, 1314, 1255, 1188
cm–1.
1H NMR (500 MHz, DMSO-d6): d = 8.64 (dd, J = 1.6, 4.3 Hz, 1 H,
H-2), 8.10 (dd, J = 1.6, 7.9 Hz, 1 H, H-4), 7.93 (d, J = 8.7 Hz, 1 H,
H-6), 7.92 (d, J = 4.8 Hz, 1 H, thiophene H-4), 7.44 (d, J = 4.8 Hz,
1 H, thiophene H-3), 7.38 (dd, J = 4.3, 7.9 Hz, 1 H, H-3), 6.79 (d,
J = 8.7 Hz, 1 H, H-5).
13C NMR (125 MHz, DMSO-d6): d = 168.4, 154.0, 146.6, 144.6,
142.8, 136.1, 131.0, 129.5, 125.0, 122.4, 117.3, 114.8, 108.6.
Anal. Calcd for C13H8N2O3S: C, 57.35; H, 2.96; N, 10.29; S, 11.78.
Found: C, 57.24; H, 2.86; N, 9.95; S, 11.49.
8-Hydroxy-7-(5-nitropyridin-2-yl)quinoline (11d)
Yield: 1.20 g (75%); orange solid; mp 242–243 °C (MeOH–H2O).
FT-IR (KBr): 3461, 1590, 1570, 1514, 1345, 1277 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 9.51 (d, J = 2.8 Hz, 1 H, pyri-
dine H-6), 8.96 (dd, J = 1.2, 4.1 Hz, 1 H, H-2), 8.74 (dd, J = 2.8, 9.0
Hz, 1 H, pyridine H-4), 8.63 (d, J = 9.0 Hz, 1H, pyridine H-3), 8.40
(dd, J = 1.2, 8.2 Hz, 1 H, H-4), 8.29 (d, J = 9.1 Hz, 1 H, H-6), 7.68
(dd, J = 4.1, 8.2 Hz, 1 H, H-3), 7.55 (d, J = 9.1 Hz, 1 H, H-5).
(10) (a) Albrecht, M.; Blau, O.; Zauner, J. Eur. J. Org. Chem.
1999, 3165. (b) Albrecht, M.; Blau, O.; Fröhlich, R. Chem.
Eur. J. 1999, 5, 48. (c) Cai, Y.-P.; Zhang, H.-X.; Xu, A.-W.;
Song, C.-Y.; Chen, C.-L.; Liu, H.-Q.; Zhang, L.; Kang, B.-
S. J. Chem. Soc., Dalton Trans. 2001, 2429. (d) Kitamura,
C.; Maeda, N.; Kamada, N.; Ouchi, M.; Yoneda, A. J. Chem.
Soc., Perkin Trans. 1 2000, 781. (e) Shen, L.; Li, F.; Sha,
Y.; Hong, X.; Huang, C. Tetrahedron Lett. 2004, 45, 3961.
(11) (a) Tang, C. V.; VanSlyke, S. A. Appl. Phys. Lett. 1987, 51,
913. (b) Tang, C. V.; VanSlyke, S. A.; Chen, C. H. J. Appl.
Phys. 1989, 65, 3610.
(12) Chen, C. H.; Shi, J. Coord. Chem. Rev. 1998, 171, 161.
(13) Uchiyama, K.; Hayashi, Y.; Narasaka, K. Synlett 1997, 477.
(14) Albrecht, M.; Blau, O. Synthesis 1997, 213.
(15) Hopkins, T. A.; Meerholtz, K.; Shaheen, S.; Anderson, M.
L.; Schmidt, A.; Kippelen, B.; Padias, A. B.; Hall, H. K. Jr.;
Peyghambarian, N.; Armstrong, N. R. Chem. Mater. 1996, 8,
344.
13C NMR (125 MHz, DMSO-d6): d = 160.3, 154.2, 148.9, 143.9,
141.9, 139.1, 136.0, 132.2, 129.9, 126.9, 123.6, 123.4, 117.8, 117.6.
Anal. Calcd for C14H9N3O3: C, 62.92; H, 3.39; N, 15.72. Found: C,
62.81; H, 3.28; N, 15.73.
8-Hydroxy-7-styrylquinoline (11e)
Yield: 1.34 g (90%); green solid; mp 139–140 °C (MeOH–H2O).
FT-IR (KBr): 3312, 1505, 1465, 1406, 1382, 1251, 1211, 966 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 10.18 (br s, 1 H, OH), 8.87 (dd,
J = 1.7, 4.0 Hz, 1 H, H-2), 8.32 (dd, J = 1.7, 8.4 Hz, 1 H, H-4), 7.91
(d, J = 8.7 Hz, 1 H, H-6), 7.67 (d, J = 16.7 Hz, 1 H, vinylic H), 7.63
(d-like, J = ca. 7.0 Hz, 2H, H-2, H-6 of C6H5), 7.54 (dd, J = 4.0, 8.4
Hz, 1 H, H-3), 7.43 (t-like, J = ca. 7.0 Hz, 2 H, H-3, H-5 of C6H5),
7.41 (d, J = 16.7 Hz, 1 H, vinylic H), 7.39 (d, J = 8.7 Hz, 1 H, H-5),
7.28 (t-like, J = ca. 7.0 Hz, 1 H, H-4 of C6H5).
13C NMR (125 MHz, DMSO-d6): d = 150.0, 148.4, 148.3, 138.6,
137.4, 136.0, 128.7, 127.9, 127.5, 126.3, 124.9, 122.8, 121.7, 119.6,
117.6.
(16) Trecourt, F.; Mallet, M.; Mongin, F.; Quéguiner, G.
Synthesis 1995, 1159.
(17) (a) Nakano, Y.; Imai, D. Synthesis 1997, 1425. (b) Shoji,
E.; Miyatake, K.; Hlil, A. R.; Hay, A. S.; Maindron, T.;
Jousseame, V.; Dodelet, J. P.; Tao, Y.; D’Iorio, M. J. Polym.
Sci. Part A: Polym. Chem. 2003, 41, 3006. (c) Pohl, R.;
Montes, V. A.; Shinar, J.; Anzenbacher, P. Jr. J. Org. Chem.
2004, 69, 1723.
MS (EI, 70 eV): m/z (%) = 246 ([M – 1]+, 23), 245 ([M – 2]+, 100),
216 (26), 207 (23), 149 (18), 108 (13), 77 (13), 51 (20), 44 (32), 43
(63).
Anal. Calcd for C17H13NO: C, 82.57; H, 5.30; N, 5.66. Found: C,
82.66; H, 4.95; N, 5.48.
(18) Pohl, R.; Anzenbacher, P. Jr. Org. Lett. 2003, 5, 2769.
Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York

1332
F. Babudri et al.
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Synthesis 2006, No. 8, 1325–1332 © Thieme Stuttgart · New York