Preparation and fungitoxicity of some dichloro-8-quinolinols

Article abstract of DOI:10.1007/PL00010246

2,5-, 3,5-, 3,7-, 4,5-, 5,6-, und 6,7-Dichloro-8-quinolinols were prepared and tested along with their 3,6-and 5,7-analogues against six fungi (Aspergillus niger, A. oryzae, Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in Sabouraud dextrose broth. Most of the compounds were strongly antifungal, inhibiting five of the fungi below 1 μg/ml. This activity is attributed to intramolecular synergism. M. cirinelloides was inhibited less by these compounds.

Full text of DOI:10.1007/PL00010246

Monatshefte fuÈr Chemie 130, 653±659 (1999)
Preparation and Fungitoxicity of Some
Dichloro-8-Quinolinols
Herman Gershon1;2;Ã, Donald D. Clarke1, and Muriel Gershon2
1
Department of Chemistry, Fordham University, Bronx, NY 10458, USA
2
New York Botanical Garden, Bronx, NY 10458, USA
Summary. 2,5-, 3,5-, 3,7-, 4,5-, 5,6-, und 6,7-Dichloro-8-quinolinols were prepared and tested along
with their 3,6- and 5,7-analogues against six fungi (Aspergillus niger, A. oryzae, Myrothecium
verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagrophytes) in
Sabouraud dextrose broth. Most of the compounds were strongly antifungal, inhibiting ®ve of the
fungi below 1 mg/ml. This activity is attributed to intramolecular synergism. M. cirinelloides was
inhibited less by these compounds.
Keywords. Dichloro-8-quinolinols; Antifungal activity; Intramolecular synergism.
È
Darstellung und Fungitoxizitat einiger Dichlor-8-chinolinole
Zusammenfassung. 2,5-, 3,5-, 3,7-, 4,5-, 5,6-, und 6,7-Dichlor-8-chinolinole wurden dargestellt und
zusammen mit ihren 3,6- und 5,7-Analoga gegenuÈber sechs Pilzen (Aspergillus niger, A. oryzae,
Myrothecium verrucaria, Trichoderma viride, Mucor cirinelloides, and Trichophyton mentagro-
È
phytes) auf Sabouraud-Dextrose-Nahrboden getestet. Die meisten Verbindungen zeigten starke
È
fungistatische Wirkung mit einer Hemmkonzentration unterhalb 1 mg/ml. Diese Aktivitat wird einer
intramolekularen Synergie zugeschrieben. M. cirinelloides wurde durch diese Verbindungen weniger
stark gehemmt.
Introduction
In the course of our studies of structure to antifungal activity relationships of 8-
quinolinol and its substituted analogues, it has been observed that 8-quinolinols
with substituents in positions 5, 6, and 7 attack different sites from each other and
from 8-quinolinol and its 2-, 3-, and 4-, substituted analogues. This was determined
by the presence or absence of synergism between pairs of compounds and by the
protection of the fungi by cysteine when the substituent was located on the pyridine
ring but not when the phenol ring was substituted [1, 2].
The enhanced activity of the disubstituted 8-quinolinols was explained on
the basis of intramolecular synergism, i.e., a mixture of minimal inhibitory
concentrations (MICs) of 5- and 7-chloro-8-quinolinols were synergistic, but when
Ã
Corresponding author

654
H. Gershon et al.
the MIC of this synergistic mixture was admixed with a MIC of 5,7-dichloro-8-
quinolinol the result was additive. The same was true for combinations of 8-
quinolinol and 5-, 6-, or 7-substituted analogues, thus allowing for the extension of
the concept of intramolecular synergism to explain the enhanced activity of the 5-,
6-, or 7-monosubstituted 8-quinolinols over 8-quinolinol [3].
It has been reported that 3,6-dichloro-8-quinolinol is the most fungitoxic
member of this class of compounds and that the dibromo analogue is less active
[4]. When combinations of analogous bromo chloro compounds were studied, 6-
bromo-3-chloro-8-quinolinol was found to be more active than its reverse analogue
[5], but less fungitoxic than 3,6-dichloro-8-quinolinol. To determine if compounds
of still greater fungitoxicity could be found, the preparation of additional dichloro-
8-quinolinols was undertaken.
Results and Discussion
The 2,5-, 3,5-, 4,5-, and 5,6-dichloro-8-quinolinols were prepared from the
respective monochloro-8-quinolinols [6] by reaction with N-chlorosuccinimide
(NCS) in 93% sulfuric acid at ambient temperatures as shown in Scheme 1. The
preparation of 3,7- and 6,7-dichloro-8-quinolinols was carried out by sulfonation of
the 3- and 6-chloro-8-quinolinols in position 5 with 18% oleum, followed by
chlorination of position 7 with NCS and desulfonation in 15% sulfuric acid in
acetic acid (Scheme 2). It should be mentioned that a side reaction took place
Scheme 1
Scheme 2

Dichloro-8-Quinolinols
655
Table 1. Antifungal activity of dichloro-8-quinolinols in Sabouraud dextrose broth at 28ꢀC in shake cultures after six days
Minimal Inhibitory Concentrations (mmol/l (mg/ml))
A. niger
A. oryzae
M. verrucaria
T. viride
M. cirinelloides T. mentagrophytes
2a
> 0.47 (> 100)a
0.093 (20)
0.042 (9)
> 0.47 (> 100)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
0.019 (4)
> 0.47 (> 100)
0.14 (30)
0.093 (20)
2b < 0.0047 (< 1)b < 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
8c
< 0.0047 (< 1)
< 0.0047 (< 1)
0.0093 (2)
< 0.0047 (< 1)
< 0.0047 (< 1)
0.0093 (2)
0.033 (7)
6a
2cd
0.28 (60)
0.028 (6)
2d < 0.0047 (< 1)
9e
< 0.0047 (< 1)
6b < 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
< 0.0047 (< 1)
0.0093 (> .2)
0.014 (3)
0.093 (20)
> 0.47 (> 100)
0.23 (50)
a
The symbol > indicates above 100 mg/ml (the highest level tested); b < indicates below 1 mg/ml (the lowest level tested);
MICs from 1±10 were obtained in increments of 1 and from 10±100 in increments if 10; c compound 8 is 3,6-dichloro-8-
quinolinol; data taken from Ref [5] except the result for T. mentagrophytes which is new; d for reproducible results, fresh
solutions had to be prepared for each test because this compound hydrolyzes on standing in DMSO; e compound 9 is 5,7-
dichloro-8-quinolinol; it was purchased from Aldrich Chemical Co.
during the chlorination of the monochloro-8-quinolinol-5-sulfonic acids. The
sulfonyl group in position 5 was replaced in part by chlorine, yielding 3,5,7-
trichloro-8-quinolinol (7) from 4a along with 5a and 5,6,7-trichloro-8-quinolinol
from 4b and 5b. These trichloro-8-quinolinols were obtained in signi®cant yield.
1H and 13C NMR data characterizing these compounds are shown in the
experimental section. As reported previously, 5-sulfonic acids cause a shift of the
proton at C-4 to higher ꢀ values than that at C-2 which generally has the highest ꢀ
value in quinolines [7]. A similar effect of a 5-sulfonyl substituent can also be seen
in the 13C NMR spectra where C-4 is shifted some 10 ppm higher than in most
nonsulfonic acids; however, it does not move to higher ꢀ values than C-2 as it does
1
in the H NMR spectra. One exception to this rule is shown by 3-chloro-8-
quinolinol-5-sulfonic acid where the 3-chloro substituent counteracts the effect of
the 5-sulfonyl substituent in the 13C NMR spectrum.
Table 1 contains a summary of the antifungal data obtained for the six
compounds in addition to the results of 3,6- and 5,7-dichloro-8-quinolinols. The
2,5-dichloro analogue was the least active of the eight compounds: not inhibiting A.
niger, T. viride, and M. cirinelloides below 100 mg/ml, but inhibiting A. oryzae
(20 mg/ml), M. verrucaria (9 mg/ml), and T. mentagrophytes (20 mg/ml). The last
three results were close to those obtained with 8-quinolinol [1]. The relatively poor
toxicity of this analogue compared with the other members of the table can be
rationalized on the basis of chlorine in position 2 yielding a compound with poor
fungitoxicity even though 5-chloro-8-quinolinol is quite fungitoxic [1]. 4,5-
Dichloro-8-quinolinol was the next least active compound, but it was at least or
more fungitoxic than any monochloro-8-quinolinol except 6-chloro-8-quinolinol
against A. niger, and 5-, 6-, and 7-chloro-8-quinolinols against T. viride. The
remaining dichloro-8-quinolinols were much more active than any monochloro-8-
quinolinol and in most cases caused complete inhibition of the fungus below 1 mg/
ml. M. cirinelloides was the most resistant organism to these compounds [1].

656
H. Gershon et al.
Since all binary combinations of monochloro-8-quinolinols formed synergistic
mixtures except for those containing 2-chloro-8-quinolinol which could not be
tested because of the inactivity of the compound, and because binary mixtures
containing 3- and 6-chloro and 5- and 7-chloro-8-quinolinols in combination with
MICs of the respective 3,6- and 5,7-dichloro-8-quinolinols showed additive
antifungal activity [3], we believe that the enhanced activity of the dichloro-8-
quinolinols tested herein is due to intramolecular synergism. The signi®cance of
intramolecular synergism is that it takes smaller amounts of xenobiotics to affect a
target cell or organism. It may also be more dif®cult for these cells to develop
resistance to a compound which attacks two sites simultaneously compared to a
material which affects only one site.
Experimental
Antifungal testing
The dichloro-8-quinolinols were tested for antifungal activity in Sabouraud dextrose broth (Difco)
according to published methods [8±11]. The six fungi employed included Aspergillus niger (ATCC
1004), A. oryzae (ATCC 1011), Myrothecium verrucaria (ATCC 9095), Trichoderma viride (ATCC
8678), Mucor cirinelloides (ATCC 7941), and Trichophyton mentagrophytes (ATCC 9129).
Compounds
Melting points were taken on a Thomas-Hoover melting point apparatus and are uncorrected. The
purity of samples was established by 1H and 13C NMR spectroscopy at 300 MHz and 75 MHz with a
Bruker DPX-300 spectrometer using DMSO-d6 as solvent and TMS as internal standard. Elemental
analyses matched the calculated values satisfactorily for 2a±d (C,H,Cl,N), 4a,b (C,H,Cl,N,S), 5a,b
(C,H,Cl,N,S), and 6a, b (C,H,Cl,N).
2,5-Dichloro-8-quinolinol (2a; C9H5Cl2NO)
To a solution of 1a [6] (2.0 g, 0.011 mol) in 40 ml of 93% sulfuric acid, NCS (1.5 g, 0.011 mol) was
added at ambient temperatures with stirring overnight. The solution was poured into 400 ml of
deionized water stirred for 10 min. The product was obtained by ®ltration, washing with deionized
water, and drying at 50ꢀC. The yield was 2.0 g (85%), m.p.: 118±120ꢀC. Steam distillation raised the
m.p. to 121±122ꢀC. The analytical sample was crystallized from acetonitrile, m.p.: 121±121.5ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.48 (d, H-4), 7.72 (d, J34 ˆ 8.89 Hz, H-3), 7.64 (d, H-6), 7.19
(d, J67 ˆ 8.37 Hz, H-7), 10.4 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 152.3 (C-8), 148.9
(C-2), 138.7 (C-8a), 136.3 (C-4), 128.0 (C-6), 125.1 (C-4a), 123.8 (C-3), 118.8 (C-5), 113.7 (C-7) ppm.
3,5-Dichloro-8-quinolinol (2b; C9H5Cl2NO)
2b was prepared from 1b [6] in the same manner as 2a was prepared from 1a. The yield of product
was 98% from a 0.011 mol run, m.p.: 152±153ꢀC. The analytical sample was crystallized from
acetonitrile, m.p.: 154±155ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.71 (d, J24 ˆ 2.26 Hz, H-2), 8.24 (d, H-4), 7.46 (d,
J67 ˆ 8.43 Hz, H-6), 6.94 (d, H-7), 10.5 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 153.1 (C-8),
147.6 (C-2), 137.1 (C-8a), 130.4 (C-4), 129.5 (C-6), 129.0 (C-3), 126.4 (C-4a), 117.6 (C-5), 112.4
(C-7) ppm.

Dichloro-8-Quinolinols
657
4,5-Dichloro-8-quinolinol (2c; C9H5Cl2NO)
2c was prepared from 1c [6] as was 2a from 1a. The product was obtained in 100% yield based on a
0.011 mol run, m.p.: 148±149ꢀC. After steam distillation the melting point was 152±154ꢀC; the
analytical sample was crystallized from acetonitrile, m.p.: 155±156ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.79 (d, J23 ˆ 4.62 Hz, H-2), 7.83 (d, H-3), 7.67 (d,
J67 ˆ 8.47 Hz, H-6), 7.16 (d, H-7), 10.3 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 153.3 (C-8),
148.0 (C-2), 140.7 (C-4), 139.9 (C-8a), 131.9 (C-6), 125.8 (C-3), 122.9 (C-4a), 116.5 (C-5), 112.2
(C-7) ppm.
5,6-Dichloro-8-quinolinol (2d; C9H5Cl2NO)
2d was prepared from 1d [6] by the same procedure as for 2a and obtained in 92% yield from a
0.011 mol run, m.p.: 149±150ꢀC. The analytical sample was crystallized from acetonitrile, m.p.:
153±154ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 9.02 (dd, J23 ˆ 4.17 Hz, J24 ˆ 1.41 Hz H-2), 8.54 (dd,
J34 ˆ 8.59 Hz, H-4), 7.81 (dd, H-3), 7.32 (s, H-7), 10.8 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-
d6): 153.5 (C-8), 149.1 (C-2), 137.9 (C-8a), 132.8 (C-4), 130.3 (C-6), 126.7 (C-4a), 123.9 (C-3),
116.5 (C-5), 112.5 (C-7) ppm.
3-Chloro-8-quinolinol-5-sulfonic acid (4a; C9H6ClNO4S)
To 14 ml of 18% oleum cooled to < 10ꢀC, 2.0 g (0.011 mol) of 3a [6] were added with stirring. When
the solution was complete, it was refrigerated overnight and then poured into a mixture of water and
ice with stirring. The crystalline precipitate was ®ltered, washed with water and acetone, and dried
on air. The yield of product was 2.76 g, (94.7%), m.p.: < 360ꢀC. An analytical sample crystallized
from aqueous DMSO melted > 360ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 9.25 (d, J24 ˆ 2.20 Hz, H-2), 10.6 (d, H-4), 7.97
(d, J67 ˆ 8.25 Hz, H-6), 7.10 (d, H-7), 5.0 (s, SO3H) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6):
153.6 (C-8), 146.1 (C-2), 135.1 (C-8a), 135.0 (C-4), 133.3 (C-5), 128.2 (C-3), 127.9 (C-6), 125.5
(C-4a), 110.5 (C-7) ppm.
6-Chloro-8-quinolinol-5-sulfonic acid (4b; C9H6ClNO4S Á 0.5H2O)
4b was prepared from 3b [6] by the same manner as 4a in 84.1% yield from a 0.018 mol run, m.p.:
230±235ꢀC. The analytical sample prepared by crystallization from aqueous DMSO melted at 232±
235ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 9.08 (dd, J23 ˆ 5.11 Hz, J24 ˆ 1.11 Hz H-2), 10.3 (dd, H-4),
8.13 (dd, J34 ˆ 9.03 Hz, H-3), 7.30 (s, H-7), 7.0 (s, SO3H) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6):
149.0 (C-8), 145.6 (C-2), 143.8 (C-4), 132.8 (C-8a), 132.3 (C-5), 129.2 (C-6), 128.1 (C-4a), 122.9
(C-3), 116.9 (C-7) ppm.
3,7-Dichloro-8-quinolinol-5-sulfonic acid (5a; C9H5Cl2NO4S)
A stirred mixture of 4a (4.0 g, 0.016 mol) and NCS (2.1 g, 0.016 mol) in 89 ml H2O was adjusted to
pH 7.0 with KOH. Stirring was continued for about 0.5 h until a negative starch iodide test was
obtained, and the solution was acidi®ed with concentrated sulfuric acid and cooled in an ice bath.
The product was obtained by ®ltration, washed with water followed by hot acetone, and dried on air.
The process may have to be repeated until the starting material is nearly completely chlorinated as
1
monitored by H NMR. The yield of product was 2.2 g (47%), m.p.: 322±325ꢀC. The analytical
sample was crystallized from water, m.p.: 323±325ꢀC.

658
H. Gershon et al.
1H NMR (300 MHz, ꢀ, DMSO-d6): 9.14 (d, J24 ˆ 2.38 Hz, H-4), 8.94 (d, H-2), 7.93 (s, H-6), 9.63
(s, SO3H) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 150.3 (C-8), 147.5 (C-2), 136.9 (C-8a), 134.0
(C-4), 133.9 (C-5), 128.5 (C-3), 127.8 (C-6), 124.0 (C-4a), 114.6 (C-7) ppm. The acetone soluble
1
product was 3,5,7-trichloro-8-quinolinol (40%) as characterized by H and 13C NMR, m.p.: 155±
159ꢀC. An independent synthesis is described below.
6,7-Dichloro-8-quinolinol-5-sulfonic acid (5b, C9H5Cl2NO4S)
5b was prepared in the same manner from 4b [6] as 5a in 65.7% yield of from a 0.012 mol run, m.p.:
182±183ꢀC. The analytical sample was prepared by crystallization from water, m.p.: 182±183ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 9.00 (dd, J23 ˆ 4.55 Hz, J24 ˆ 1.10 Hz, H-2), 10.05 (dd, H-4),
7.88 (dd, J34 ˆ 8.2 Hz, H-3), 5.0 (s, SO3H) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 148.2 (C-8),
146.3 (C-2), 142.0 (C-4), 134.1 (C-8a), 132.8 (C-5), 130.6 (C-6), 125.6 (C-4a), 122.5 (C-3), 119.1
(C-7) ppm.
1
The acetone soluble product was 5,6,7-trichloro-8-quinolinol (20%) as characterized by H and
13C NMR, m.p.: 210±214ꢀC (Ref. [12]: m.p.: 213±214ꢀC, Ref. [13]: 220±225ꢀC); 1H NMR
(300 MHz, ꢀ, DMSO-d6): 9.02 (dd, J23 ˆ 4.15 Hz, J24 ˆ 1.15 Hz, H-2), 8.55 (dd, H-4), 7.81
(dd, J34 ˆ 8.66 Hz, H-3), 11.4 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 150.5 (C-8), 150.0
(C-2), 137.1 (C-8a), 133.1 (C-4), 129.6 (C-6), 124.7 (C-4a), 124.1 (C-3), 118.0 (C-5), 115.4
(C-7) ppm.
3,7-Dichloro-8-quinolinol (6a; C9H5Cl2NO)
5a (2.5 g, 0.012 mol) was heated under re¯ux with stirring in 25 ml of 15% H2SO4 in acetic acid
overnight. The solution was poured into 250 ml of water and adjusted to pH 7 with NH3. After
cooling in an ice bath with stirring the product was obtained by ®ltration, washed with deionized
water, and dried at 50ꢀC overnight. The yield of 6a was 1.6 g (88.9%), m.p.: 162±165ꢀC. An
analytical sample was crystallized from acetonitrile, m.p.: 170±171ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.88 (d, J24 ˆ 2.31 Hz, H-2), 8.55 (d, H-4), 7.64 (d,
J56 ˆ 8.85 Hz, H-6), 7.43 (d, H-5), 11.0 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 149.5 (C-8),
147.6 (C-2), 136.9 (C-8a), 134.5 (C-4), 129.8 (C-6), 128.2 (C-3), 127.8 (C-4a), 117.6 (C-5) 116.8
(C-7) ppm.
6,7-Dichloro-8-quinolinol (6b; C9H5Cl2NO)
6b was prepared from 5b in the same manner as 6a in 98.6% yield from a 0.01 mol run, m.p.: 185±
188ꢀC. The analytical sample was crystallized from acetonitrile, m.p.: 191±192ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.94 (dd, J23 ˆ 4.12 Hz, J24 ˆ 1.41 Hz, H-2), 8.36 (dd, H-4),
7.74 (dd, J34 ˆ 8.7 Hz, H-3), 10.8 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 151.3 (C-8), 149.3
(C-2), 137.1 (C-8a), 135.6 (C-4), 130.2 (C-6), 126.9 (C-4a), 123.0 (C-3), 117.5 (C-5), 114.9 (C-7)
ppm.
3,5,7-Trichloro-8-quinolinol (7; C9H4Cl3NO)
7 was prepared from 1b [6] by the same method as 2b except that two equivalents of NCS were
employed in the chlorination. A 0.011 mol run yielded 99% of product, m.p.: 146±149ꢀC, and the
analytical sample crystallized from acetonitrile melted at 159±160ꢀC.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.92 (d, J24 ˆ 1.87 Hz, H-2), 8.42 (d, H-4), 7.81 (s, H-6), 11.2
(s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 149.3 (C-8), 148.5 (C-2), 137.0 (C-8a), 130.9 (C-4),
129.7 (C-3), 129.1 (C-6), 125.2 (C-4a), 117.9 (C-5), 116.4 (C-7) ppm.

Dichloro-8-Quinolinols
659
3,6-dichloro-8-quinolinol (8; C9H5Cl2NO)
8 was prepared as described previously [5].
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.82 (d, J24 ˆ 2.20 Hz, H-2), 8.46 (d, H-4), 7.48 (d,
J57 ˆ 2.2 Hz, H-5), 7.18 (d, H-7), 10.7 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 154.9 (C-8),
147.1 (C-2), 135.6 (C-8a), 133.5 (C-4), 132.9 (C-6), 129.1 (C-4a), 129.7 (C-3), 115.8 (C-5), 112.7
(C-7) ppm.
5,7-Dichloro-8-quinolinol (9; C9H5Cl2NO)
9 was obtained from Aldrich Chemical Co.
1H NMR (300 MHz, ꢀ, DMSO-d6): 8.98 (dd, J23 ˆ 4.12 Hz, J24 ˆ 1.41 Hz, H-2), 8.46 (dd, H-4),
7.72 (dd, J34 ˆ 8.7 Hz, H-3), 7.75 (s, H-6), 10.8 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6):
149.2 (C-8), 149.8 (C-2), 138.9 (C-8a), 132.8 (C-4), 127.7 (C-6), 124.7 (C-4a), 123.1 (C-3), 118.9
(C-5), 115.5 (C-7) ppm.
For comparison with all of the above, the NMR spectra of 8-quinolinol obtained from Aldrich
1
were recorded. H NMR (300 MHz, ꢀ, DMSO-d6): 8.91 (dd, J23 ˆ 4.0 Hz, J24 ˆ 1.5 Hz, H-2), 8.36
(dd, H-4), 7.57 (dd, J34 ˆ 8.5 Hz, H-3), 7.48 (dd, J56 ˆ 8.1 Hz, J57 ˆ 1.1 Hz, H-6), 7.46 (dd, H-5),
7.22 (dd, J67 ˆ 7.8 Hz, H-7), 9.90 (s, OH) ppm; 13C NMR (75 MHz, ꢀ, DMSO-d6): 153.2 (C-8), 148.2
(C-2), 138.7 (C-8a), 136.0 (C-4), 127.5 (C-6), 128.8 (C-4a), 121.8 (C-3), 117.8 (C-5), 111.3 (C-7)
ppm.
Acknowledgements
Partial support for this work was provided by the National Science Foundation's Division of
Undergraduate Education through grant DUE #9650684.
References
[1] Gershon H, Clarke DD, Gershon M (1991) J Pharm Sci 80: 542
[2] Gershon H, Clarke DD, Gershon M (1994) Monatsh Chem 125: 51
[3] Gershon H, Gershon M (1995) Monatsh Chem 126: 1303
[4] Gershon H, Clarke DD, Gershon M (1994) Monatsh Chem 125: 723
[5] Gershon H, Clarke DD, Gershon M (1996) Monatsh Chem 127: 331
[6] Gershon H, Clarke DD (1991) Monatsh Chem 122: 935
[7] Gershon H, Clarke DD, Gershon M (1995) Trends in Heterocyclic Chem 4: 1
[8] Gershon H, Shanks L (1981) Can J Microbiol 27: 612
[9] Gershon H, Gre®g AT, Cady DJ (1985) Can J Microbiol 31: 707
[10] Gershon H, Clarke DD, Gershon M (1989) J Pharm Sci 78: 975
[11] Gershon H, Clarke DD, Gershon M (1993) Monatsh Chem 124: 367
[12] Hebenbrand A (1888) Chem Ber 21: 2977
[13] Burckhalter JH, Stephens VC, Scarborough HC, Brinigar WS, Edgerton WH (1959) J Am Chem
Soc 76: 4902
Received October 19, 1998. Accepted (revised) November 20, 1998