Synthesis of novel 5,7-disubstituted 8-hydroxyquinolines

Article abstract of DOI:10.1002/jhet.5570450411

(Chemical Equation Presented) Seven new 5,7-disubstituted oxine derivatives have been synthesized via a Mannich reaction between a sec. amine (e.g. piperidine, pyrrolidine, morpholine, or dibenzylamine,) and 5-cyano or 5-azidomethyl-8-hydroxyquinoline, which were respectively obtained by nucleophilic displacement of 5-chloromethyl-8-hydroxyquinoline by cyanide or azide anions. In all cases, a single product was isolated in medium to fair yield and characterized on the basis of ¹H and ¹³C-NMR, MS and IR spectrometric data. The X-ray structure of the product obtained from 5-cyanomethyl-8-hydroxyquinoline and piperidine is also reported.

Full text of DOI:10.1002/jhet.5570450411

Jul-Aug 2008
1023
Synthesis of Novel 5,7-Disubstituted 8-Hydroxyquinolines
Banacer Himmi [a,c], Jean-Pierre Joly [b], Fouzia Hlimi [c], Mohamed Soufiaoui [c]
Saïd Kitane [a], Abdelmejid Bahloul [d], Abdelhamid Eddaif [a], Abdelfatah Sebban [d]
[a] Laboratoire de Chimie Appliquée, Ecole Nationale de l'Industrie Minérale, BP 753, Agdal, Rabat, Morocco.
[b] Groupe SUCRES, UMR 7565 Nancy-Université, CNRS, BP 239, F-54506 Vandœuvre-lès-Nancy, France.
[c] Laboratoire de chimie des plantes et de synthèse organique et bioorganique,
Département de chimie, Faculté des sciences, Rabat, Morocco.
[d] Laboratoire de chimie des polymères et de synthèse organique, Faculté des Sciences Ben M'sik,
Université Hassan II-Mohammedia, Casablanca, Morocco.
Received May 15, 2007
R1
R1
(CH2O)n
R2
sec. amine
40-81%
N
N
OH
OH
R
1 = CN, N3
R2 = piperidinyl, pyrrolidinyl, morpholinyl, dibutylamino
Seven new 5,7-disubstituted oxine derivatives have been synthesized via a Mannich reaction between a
sec. amine (e.g. piperidine, pyrrolidine, morpholine, or dibenzylamine,) and 5-cyano or 5-azidomethyl-8-
hydroxyquinoline, which were respectively obtained by nucleophilic displacement of 5-chloromethyl-8-
hydroxyquinoline by cyanide or azide anions. In all cases, a single product was isolated in medium to fair
1
yield and characterized on the basis of H and 13C-NMR, MS and IR spectrometric data. The X-ray
structure of the product obtained from 5-cyanomethyl-8-hydroxyquinoline and piperidine is also reported.
J. Heterocyclic Chem., 45, 1023 (2008).
INTRODUCTION
hydrometallurgy and for analytical chemistry purposes
[4]. Additionally some of these compounds are endowed
with interesting biological activities when associated with
metals or as metal-free chelators [5]. We report here about
the synthesis of novel 5,7-disubstituted derivatives of
oxine using the Mannich reaction.
The present work is connected to our previous
contributions in the field of 8-hydroxyquinoline (= oxine)
derivatives and their use as biologic or complexing tools
[1]. It is well known that oxine is an excellent metal ion
chelator [2]. However, unsubstituted oxine is too much
water-soluble for practical liquid-liquid extraction.
Therefore high lipophilic substituted oxines [3] have been
synthesized to obviate this problem: for example,
sparingly water-soluble but highly soluble in organic
media 7-substituted derivatives of oxine, such as Kelex
100™ and aminoethylenes, have demonstrated superior
extraction behaviors and are thoroughly used in
RESULTS AND DISCUSSION
5-Cyanomethyl-8-hydroxyquinoline 2a was synthesized
according to the method reported by Warner et al. [5a]. 5-
Chloromethyl-8-hydroxyquinoline hydrochloride
1 [6]
underwent rapid and exothermic nucleophilic displacement
by an excess of potassium cyanide in dimethylsulfoxide
Table 1
1H-nmr data of oxines 2a and 2b (in DMSO-d6).
oxine
R1
H-2
H-3
H-4
H-6
H-7
CH2R1
2a
CN
8.92
7.65
8.43
7.54
(d, 1H)
7.51
7.15
(d ,1H)
7.18
4.35
(s, 2H)
4.84
(dd, J2-3 4.3 Hz) (dd, J3-4 8.7 Hz) (dd, J2-4 1.4 Hz)
8.95 7.66 8.53
2b
N3
(dd, J2-3 4.4 Hz) (dd, J3-4 8.8 Hz) (dd, J2-4 1.5 Hz)
(d, 1H)
(d, 1H)
(s, 2H)
Table 2
13C-nmr data of oxines 2a and 2b (in DMSO-d6)*.
oxine
C-2
C-3
C-4
C-4a
C-5
C-6
C-7
C-8
C-8a
C-5a
2a
2b
148.2
148.3
119.1
121.5
132.1
132.8
128.0
129.7
126.4
127.2
19.3
51.0
122.1
122.3
110.6
110.4
153.4
154.1
138.7
138.9
* For omitted CN signal see experimental details

1024
B. Himmi, J.-P. Joly, F. Hlimi, M. Soufiaoui, S. Kitane, A. Bahloul, A. Eddaif, and A. Sebban
Vol 45
Scheme 1
(DMSO) at 90°C to give 2a in good yield. The IR-spectra
of the purified product exhibits the characteristic CꢀN
stretching vibration at 2260 cm-1. As depicted in Table 1,
R1
R1
Cl
5a
5a
1
4
4
5
5
the H-NMR spectrum displays a characteristic singlet at
4a
4a
6
7
3
2
3
2
6
(CH2O)n
KCN
4.35 ppm integrating for the two benzylic protons, two
signals at 7.15 and 7.54 ppm for H-6 and H-7 respectively,
and a broad signal around 10 ppm attributed to the phenolic
proton. The 13C-NMR spectra, displays the expected nitrile
peak at 116.9 ppm and one up-field resonance at 19.3 ppm
assigned to the vicinal benzylic carbon.
or NaN3
R2
7
sec. amine
8a
8a
N
N
N
8
8
7a
OH
OH
OH
84-90%
40-81%
2a : R1 = CN
2b : R1 = N3
a
b
c
1
3a: R1 = CN; R2 =
N
a
b
3b: R1 = CN; R2 = N
5-Azidomethyl-8-hydroxyquinoline 2b was isolated in
good yield from 1 via a classical azide displacement in
refluxing acetone [7]. The IR-spectra of 2b exhibits the
intense characteristic N3-stretching vibration at 2090 cm-1
a
b
3c: R1 = CN; R2
=
N
O
3d: R1 = N3; R2 = N
3e: R1 = N3; R2 = N
1
and the H-NMR spectrum displays the expected singlet
integrating for two benzylic protons at 4.8 ppm and 2
signals at 7.18 and 7.51 ppm for H-6 and H-7 respectively.
Compared to precursor 2a, the benzylic carbon is down-
shielded to 51.0 ppm in 2b. The pharmaceutical activities of
2a and 2b following oral administration in mice were
investigated [8]. The complexing ability of 2b towards
Zn(II) has been recently evaluated elsewhere [9].
3f: R1 = N3; R2 =
3g: R1 = CN; R2
N
N
O
Ph
Ph
=
a
Aminomethylation of adducts 2a & 2b by secondary amines.
As outlined in Scheme 1, the reaction of phenols 2a and
2b with different secondary amines (i.e. piperidine,
pyrrolidine, morpholine, and dibutylamine) under the
conditions of the Mannich reaction in refluxing ethanol
yields seven new products 3a-g. The structure of these
solely ortho-substituted products isolated in medium to
fair yield was established on the basis of their
spectroscopic data and furthermore fully ascertained by
the X-ray molecular structure of 3a. All IR-spectra
display the expected set of characteristic bands in the
region 2800-2980 cm-1 corresponding to the C-H valence
stretching vibrations of the benzylic protons on C-5a and
C-7a, and those of the amine. The H-7 doublet, around 7.2
ppm for the precursors 2a and 2b disappeared whereas the
H-6 doublet turned into a singlet around 7.4 ppm in all 1H
NMR spectra of the products. NMR-data of the target
compounds 3a-g are summarized in Table 3 and 4.
Table 3
1H-nmr data of products 3a-g (in DMSO-d6 except 3g in CDCl3).
Product
H-2
H-3
H-4
H-6
CH2R1
CH2R2
H-a
H-b
H-c
3a
8.97
(dd, J2-3
4.3 Hz)
8.96
(dd, J2-3
4.4 Hz)
8.94
(dd, J2-3
4.5 Hz)
8.95
(dd, J2-3
4.2 Hz)
8.88
(dd, J2-3
4.4 Hz)
8.94
(dd, J2-3
4.3 Hz)
8.93
7.56
(dd, J3-4 8.7
Hz)
8.38
(dd, J2-4
1.4 Hz)
8.49
(dd, J2-4
1.5 Hz)
8.45
(dd, J2-4
1.6 Hz)
8.44
(dd, J2-4
1.4 Hz)
8.43
(dd, J2-4
1.5 Hz)
8.35
(dd, J2-4
1.4 Hz)
8.13
7.49
(s, 1H)
4.43
(s, 2H)
3.72
(s, 2H)
2.42
(s, 4H)
1.48
(s, 4H)
1.39
(s, 2H)
3b
3c
3d
3e
3f
7.57
7.58
(s, 1H)
4.42
(s, 2H)
3.78
(s, 2H)
2.55
(s, 4H)
1.76
(s, 4H)
-
-
(dd, J3-4 8.8
Hz)
7.58
(dd, J3-4 8.9
Hz)
7.53
(dd, J3-4 8.6
Hz)
7.67
(dd, J3-4 8.8
Hz)
7.49
(dd, J3-4 8.7
Hz)
7.49
(dd, J3-4 8.8
Hz)
7.56
(s, 1H)
4.48
(s, 2H)
3.72
(s, 2H)
3.61
(s, 4H)
2.47
(s, 4H)
7.29
(s, 1H)
4.44
(s, 2H)
3.73
(s, 2H)
2.45
(s, 4H)
1.48
(s, 4H)
1.35
(s, 2H)
7.57
(s, 1H)
4.46
(s, 2H)
3.89
(s, 2H)
2.55
(s, 4H)
1.32
(s, 4H)
-
-
-
7.34
(s, 1H)
4.63
(s, 2H)
3.88
(s, 2H)
3.77
(s, 4H)
2.63
(s, 4H)
3g
7.27
(s, 1H)
4.02
(s, 1H)
3.91
(s, 1H)
3.69
(s, 4H)
-
(dd, J2-3
4.4 Hz)
(dd, J2-4
1.5 Hz)

Jul-Aug 2008
Synthesis of Novel 5,7-Disubstituted 8-Hydroxyquinolines
1025
Table 4
13C-nmr selected data of products 3a-c (in DMSO-d6) and 3f-g (in CDCl3)*.
Product
C-2
C-3
C-4
C-4a
C-5
C-5a
C-6
C-7
C-8
C-8a
3a
3b
3c
3f
148.4
148.3
148.4
148.9
149.0
119.5
119.5
119.2
121.0
121.9
132.2
132.2
132.3
132.1
130.8
125.5
125.4
125.5
126.6
125.8
116.4
116.4
116.6
116.6
117.7
19.5
19.5
19.5
52.3
20.7
129.1
129.2
129.6
129.7
128.5
121.8
121.8
121.9
121.9
118.7
151.8
151.2
151.4
153.3
153.1
138.7
138.7
138.6
139.5
139.4
3g
* For omitted signals see experimental details
Table 5
Crystal data and structure refinement of 3a
Empirical formula
Formula weight
Wavelength
C17H19N3O
281.35
0.71073 Å
Monoclinic, P21/c
Crystal system, space group
Unit cell dimensions
a (Å)
12.6714 (3)
11.8221 (2)
10.7275 (2)
111.481 (8)
1495.38 (5)
4
b (Å)
C (Å)
ꢀ (°)
Volume (Å3)
Z
Calculated density
Absorbtion coefficient
F(1000)
1.25
0.160
934
Crystal size (mm)
ꢁ Range for data collection
Reflection collected / unique
Completeness to ꢁ = xx.yy
Refinement method
Data / restraints /parameters
Goodness-of-fit on F2
Final R indices [I > 2ꢀ(I)]
R indices (all data)
0.20 ꢀ 0.18 ꢀ 0.16
2.44-29.04 ꢁ
9679
99.76%
Full-matrix least-square on F2
3982 / 0/ 266
1.046
Figure 1. Molecular configuration and atom numbering scheme for 3a
showing 50% probability ellipsoids.
R1 = 0.0468
0.0757
The slow evaporation of a saturated solution of 3a in
ethanol at 4°C in the dark yielded single crystals suitable
for X-ray diffraction. The measurements were carried out
on a Bruker Nonius Kappa CCD area diffractometer at
room temperature. The structure solved by direct methods
[10] and refined by full-matrix least squares [11] is given
in Figure 1 (vide supra). The colorless crystals are
monoclinic, space group P21/c with 4 formula units per
unit-cell. The crystal data and details of the X-ray analysis
are listed in Table 5. One hydrogen-bonding association
exists in the solid-state crystal structure between the
phenolic OH and the pyridine nitrogen atom (N1). The
bond lengths are 1.004 Å and 1.715 Å for O1 H1 and
N1 H1 respectively and the O1 H1 N1 angle is 147.7°.
The crystallographic-information-file (CIF) has been
deposited with the The Cambridge Crystallographic Data
Centre as supplementary data under the reference CCDC
680528. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif.
CONCLUSION
During this work, we succeeded in synthesizing seven
new 8-hydroxyquinoline derivatives by a Mannich
reaction from 5-cyano and 5-azidomethyl-8-hydroxy-
quinoline with piperidine, pyrrolidine, morpholine or
dibenzylamine. In all cases, a single product was isolated
in medium to fair yield and characterized by suitable
spectroscopies. The molecular structure of one of these C-
ortho-substituted phenol (3a) could be fully ascertained
by X-ray diffraction. These new compounds are currently
evaluated for their complexing and biological properties
as antibacterial or fungicide agents.
EXPERIMENTAL
Melting points were measured with a Buchi 510 apparatus and
are uncorrected. Nmr spectra were recorded in DMSO-d6 or
CDCl3 using a Bruker AC200 spectrometer operating at 200

1026
B. Himmi, J.-P. Joly, F. Hlimi, M. Soufiaoui, S. Kitane, A. Bahloul, A. Eddaif, and A. Sebban
Vol 45
MHz for H and 50 MHz for 13C. Assignments of the various
protons were supported by successive irradiations. IR spectra
were recorded on a Perkin Elmer 577 spectrometer, solid
products being palletized in KBr. Elemental analyses were
carried out by the ‘Service de Microanalyse’ of the ‘Institut de
Chimie des Substances Naturelles’ in Gif-sur-Yvette, France.
Esi+-HRMS were performed on a QTOF micro Waters MS-
spectrometer at the University Blaise Pascal in Clermont
Ferrand, France and ms-IE+ on a Polaris thermo-electron MS-
spectrometer at the UATRS/CNRS in Rabat, Morocco.
mmoles of 2a); mp 138°C; IR: 2307 cm-1 (CꢀNstretching); 1H nmr,
1
see Table 3; 13C nmr, see Table 4; other 13C nmr signals: 119.3
(CN), 56.7 (C7a), 66.3 (Ca), 53.3 (Cb). Anal. Calcd. for
C16H17N3O2: C, 67.83; H, 6.05; N, 14.83. Found: C, 67.75; H, 5.99;
N, 14.77. EI+-ms: m/z (26) 283.93 [M+H]+, 275.76 (16), 198.06
(52), 156.94 (58), 130.14 (14), 88.11 (32), 79.08 (100), 61.15 (20).
5-Azidomethyl-7-piperidinomethyl-8-hydroxyquinoline 3d
was obtained as an orange hygroscopic gum in 81% yield (1.2 g
1
from 5.0 mmoles of 2b); IR: 2096 cm-1 (N3 stretching); H nmr,
see Table 3. ESI+-ms: m/z 297.95 (2) [M+H]+, 163.88 (22),
156.88 (100), 130.11 (10), 100.14 (10), 98.12 (16), 86.12 (48),
84.12 (76), 79.07 (58), 61.09 (14). ESI+-hrms: m/z 298.1609
[M+H]+.
5-Cyanomethyl-8-hydroxyquinoline (2a). 5-Chloromethyl-
8-hydroxyquinoline•HCl 1 [6] (4.60 g, 20 mmoles) were
carefully added over 15 min into a solution of KCN (3.9 g, 3.0
eq) in dry DMSO (50 mL) at 90°C under Ar under an efficient
fume board. The mixture was stirred under 95°C for 1 hour,
allowed to cool to rt, poured onto 100 mL of chilled water. The
precipitate was filtered on a sintered glass and thoroughly
washed with cold water, dried in vacuo to yield the nitrile 2a
(3.12 g, 84%) as a brown solid used without further purification
for the Mannich reaction; mp 179-180°C (benzene, Litt. [5a]
5-Azidomethyl-7-pyrrolidinomethyl-8-hydroxyquinoline
3e was obtained as a dark hygroscopic gum in 60% yield (177
1
mg from 2.5 mmoles of 2b); IR: 2106 cm-1 (N3 stretching); H-
nmr, see Table 3. ESI+-ms: m/z 283.05 (2) [M]+, 172.06 (14),
159.05 (48), 156.93 (30), 130.12 (40), 117.12 (28), 89.10 (12),
79.07 (100), 61.09 (16). ESI+-hrms: m/z 284.1507 [M+H]+.
5-Azidomethyl-7-morpholinomethyl-8-hydroxyquinoline
3f was obtained as a yellow solid in 40% yield (300 mg from 2.5
178-180°C); IR: 2260 cm-1; H and 13C nmr, see Table 1 & 2.
1
Other 13C nmr signal: 116.9 (CN). EI+-ms: m/z 184.06 (44) [M]+,
183.09 (26), 155.11 (54), 130.15 (30), 79.09 (100), 61.12 (20).
5-Azidomethyl-8-hydroxyquinoline (2b). A mixture of 5-
chloromethyl-8-hydroxyquinoline•HCl 1 (4.60 g, 20 mmoles) and
NaN3 (7.84 g, 3 eq) in abs. acetone (100 mL) was refluxed for 20
hours under controlled atmosphere (N2). After cooling, the solvent
was evaporated under reduced pressure and the residue partitioned
between CHCl3/H2O (150 mL, 1:1). The organic phase was isolated,
washed with water (3ꢀ20 mL), dried (Na2SO4), and finally
concentrated in vacuo to yield the azide 2b as a grey solid (3.12 g,
90%) used without further purification for the Mannich reaction; mp
110°C (benzene); IR: 2090 cm-1; 1H and 13C nmr, see Table 1 & 2.
Anal. Calcd. for C10H8N4O: C, 59.99; H, 4.03; N, 27.99. Found: C,
59.04; H, 3.93; N, 27.36. EI+-ms: m/z 200.97 (14) [M+H]+, 158.05
(92), 156.91 (100), 130.14 (20), 79.06 (82), 61.07 (26).
mmoles of 2b); mp 134°C; IR: 2097 cm-1 (N3 stretching); H
1
nmr, see Table 3; 13C nmr, see Table 4; other 13C nmr signals:
59.7 (C7a), 66.9 (Ca), 53.2 (Cb). Anal. Calcd. for C15H17N5O2:
C, 60.19; H, 5.72, N, 23.40. Found: C, 60.14; H, 5.68, N, 23.26.
EI+-ms: m/z 257.1 (27) [M-N3] +, 202.1 (100).
5-Cyanomethyl-7-(N,N-dibutylamino)methyl-8-hydroxy-
quinoline 3g was obtained as pale yellow needles in 65% yield
(640 mg from 2.5 mmoles of 2a); mp 113°C; IR: 2102 cm-1 (CꢀN
1
stretching); H nmr, see Table 3; 13C nmr, see Table 4; other 13C
nmr signals: 137.4, 129.5, 128.7 (Ar.), 115.3 (CN), 58.3 (Ca), 54.9
(C7a). Anal. Calcd. for C26H23N3O: C, 79.36; H, 5.89, N, 10.68.
Found: C, 79.11; H, 5.79, N, 10.56. EI+-ms: m/z 394.19 (52)
[M+H]+, 350.97 (64), 243.12 (100), 198.13 (93), 141.00 (28).
REFERENCES AND NOTES
General procedure for the Mannich reaction. An
equimolar mixture of the substrate (2a or 2b), paraformal-
dehyde, and the sec. amine in abs. EtOH (30 mL) was refluxed
for 4 hours under controlled atmosphere (N2). After cooling, the
solvent was evaporated under reduced pressure and the resulting
solid isolated on a sintered glass, washed with cold ether (ca. 30
mL), and finally dried in vacuo. When possible, analytical
samples were obtained by crystallization from EtOH.
5-Cyanomethyl-7-piperidinomethyl-8-hydroxyquinoline 3a
was obtained as a brown solid in 78% yield (620 mg from 2.7
mmoles of 2a); mp 150°C; IR: 2270 cm-1 (CꢀN stretching); 1H
nmr, see Table 3; 13C nmr, see Table 4; other 13C nmr signals:
119.4 (CN), 57.5 (C7a), 53.9 (Ca), 25.6 (Cb), 23.9 (Cc). Anal.
Calcd. for C16H17N3O: C, 72.57; H, 6.81. N, 14.94. Found: C,
72.53; H, 6.71; N, 14.87. ESI+-hrms: m/z 282.1609 (13)
[M+H]+, 197.0697 (100) [M-C5H10N]+, 158.9972 (5).
[1a] Skalli, B.; El Kacemi, K.; Belcadi, S.; Bahloul, A.; Kitane,
S.; Marouf, B. Quim. Anal. 1998, 17, 83-88. [b] Bahloul, A.; Sebban, A.;
Dardari, Z.; Boudouma, M.; Kitane, S.; Belghiti, T.; Joly, J.-P. J.
Heterocycl. Chem. 2003, 40, 243-248. [c] Dardari, Z.; Lemrani, M.;
Bahloul, A.; Sebban, A.; Hassar, M.; Kitane, S.; Berrada, M.;
Boudouma, M. Farmaco 2004, 59, 195-199.
[2] Borrel, M.; Paris, R. C. Anal. Chim. Acta 1950, 4, 267-285.
[3] Sparfel, D.; Cote. G. Solvent Extr. Ion Exch. 2004, 22, 1-12.
[4a] Helgorsky, J. ; Lévèque, A. Sci. Tech. (Paris) 1978, 52, 19-
27. [b] Matsumiya, H.; Ohkouchi, R.; Hiraide, M. Anal. Chim. Acta
2006, 556, 438-443.
[5a] Warner, V. D.; Sane, J. N.; Mirth, D. B.; Turesky, S. S.;
Soloway, B. J. Med. Chem. 1976, 19, 167-169. [b] Rehmani, F. S.;
Fateh, I. A. J. Chem. Soc. Pak. 2005, 27, 263-267.
[6] Burckhalter, J. H.; Leib, R. I. J. Org. Chem. 1961, 26, 4078-
4083.
[7a] Curtius, T.; Ehrhart, G. Ber. B 1922, 55, 1559-1571; [b]
Cremlyn, R. J. W. Aust. J. Chem. 1973, 26, 1591-1593.
[8] Himmi, B.; Faouzi, My A.; Akioud, M.; Kitane, S.; Edaiff,
A.; Soufiaoui, M.; Ghoulidi, S. ; Bahloul, A. ; Sebban, Et A.; Cherrah,
Y. BioChem. (Rajkot, India) 2007, 1, 122-125.
[9] Himmi, B.; Messnaoui, B.; Kitane, S.; Eddaif, A.; Alaoui, A.;
Bouklouze, A.; Soufiaoui. M. Hydrometallurgy, in press.
[10] Sheldrick, G. SHELXS-97: Program for Crystal Structure
Solution, University of Göttingen, 1997.
5-Cyanomethyl-7-pyrrolidinomethyl-8-hydroxyquinoline
3b was obtained as a brown solid in 69% yield (620 mg from 2.7
mmoles of 2a); mp 110°C; IR: 2252 cm-1 (CꢀN stretching); 1H
nmr, see Table 3; 13C nmr, see Table 4; other 13C nmr signals:
119.4 (CN), 53.9 (C7a), 53.6 (Ca), 23.3 (Cb). EI+-ms: m/z
267.99 (22) [M+H]+, 198.05 (16), 156.93 (42), 130.12 (12),
86.14 (14), 84.13 (18), 79.07 (100), 70.18 (82), 61.15 (18);
ESI+-hrms: m/z 268.1442 [M+H]+; X-ray structure, see Fig. 1.
5-Cyanomethyl-7-morpholinomethyl-8-hydroxyquinoline
3c was obtained as a beige solid in 77% yield (590 mg from 2.7
[11] Sheldrick, G. SHELXL-97: Program for Crystal Structure
Refinement, University of Göttingen, 1997.