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2077
in the selective reduction of the 4-hydrazinoquinoline
group in the presence of halo (fluoro and chloro), alkoxy
and methylendioxy groups.23 To further explore the com-
patibility of this reduction procedure with different func-
tional groups, we used the commercially available
4-hydrazinobenzoic acid, its corresponding ethyl ester
and the bromophenyl hydrazine (4a–c) as a substrate.
Following the same protocol, the reduction reaction
smoothly took place to afford the corresponding anilines
5a–c (Table 1) in high yield.
9. Savini, L.; Chiasserini, L.; Gaeta, A.; Pellerano, C. Bioorg. Med.
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Barzi, A.; Nocentini, G. Eur. J. Med. Chem. 1995, 30, 547–552.
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Concluding, we have developed a convenient and rapid
method for the conversion of 4-chloroquinolines,
9-chloroacridines and 9-chloro-1,2,3,4-tetrahydroacridine
derivatives to the corresponding 4-amino- and 9-amino-
analogues through a two-step sequence involving the
microwave-assisted formation of 4-hydrazino intermedi-
ates followed by their reduction with nickel boride. To
the best of our knowledge, this is the first nickel boride cat-
alyzed reduction of monosubstituted hydrazines. More-
over, the entire protocol provides a rapid and efficient
access to 4-aminoquinolines, while avoiding the use of
harsh and hazardous conditions previously used to synthe-
size this class of compounds. When developing antimalarial
quinolines, this synthetic strategy may reduce costs and
reaction time.
15. Ganem, B.; Osby, J. O. Chem. Rev. 1986, 86, 763–780.
16. Khurana, J. M.; Gogia, A. Org. Prep. Proced. Int. 1997, 29, 1–32.
17. Nose, A.; Kudo, T. Chem. Pharm. Bull. 1981, 29, 1159–1161.
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19. Khurana, J. M.; Kandpal, B. M.; Kukreja, G.; Sharma, P. Can. J.
Chem. 2006, 84, 1019–1023.
20. Khurana, J. M.; Kukreja, G.; Bansal, G. J. Chem. Soc., Perkin Trans.
1 2002, 2520–2524.
21. Khurana, J. M.; Kukreja, G. Synth. Commun. 2002, 32, 1265–1269.
22. Microwave reactions were conducted using a CEM Discover Synthe-
sis Unit (CEM Corp., Matthews, NC). The machine consists of a
continuous focused microwave power delivery system with operator
selectable power output from 0 to 300 W. The reaction was performed
in glass vessels (capacity 10 mL) sealed with a septum. The temper-
ature of the contents of the vessel was monitored using a calibrated
infrared temperature control mounted under the reaction vessel. All
experiments were performed using a stirring option whereby the
contents of the vessel are stirred by means of a rotating magnetic plate
located below the floor of the microwave cavity and a Teflon-coated
magnetic stir bar in the vessel. In a typical experiment, a suspension of
4-chloroquinoline-derivative (500 mg) and hydrazine monohydrate
(2 equiv) was irradiated in a sealed tube at 150 W for 5 min (ramp
time 30 s, Tmax = 150 °C, Pmax = 200 psi, Power max = on). After
cooling to rt, the resulting solid was isolated by filtration and
crystallized from ethanol. Physical and spectroscopic data of hydra-
zines 2a–l are consistent with those reported in the literature.
23. In a typical procedure, to a mixture of 4-hydrazino-derivative
(100 mg), nickel(II) chloride hexahydrate (1 equiv) in methanol
(4 mL), was added sodium borohydride (3 equiv) very cautiously
while stirring the reaction mixture vigourously at room temperature.
The progress of the reaction was monitored by TLC (10:1 CH2Cl2/
MeOH). After the complete disappearance of the starting material,
the reaction mixture was filtered through a Celite pad. The filtrate was
diluted with water and extracted with ethyl acetate. The combined
organic extracts were dried over Na2SO4, filtered and concentrated in
vacuo. The crude products were purified over neutral alumina column
using 0.5% MeOH/CH2Cl2 to afford the pure compounds. Spectro-
scopic data for the new compounds: 3f: 1H NMR (CDCl3) d 1.44 (t,
J = 1.4, 5.6 Hz, 3H); 4.12 (q, J = 1.5, 5.6 Hz, 2H); 4.8 (s, 2H); 6.45
(dd, J = 1.2, 4.1 Hz, 1H); 7.05 (d, J = 5.2 Hz, 1H); 7.28 (d,
J = 2.6 Hz, 1H); 7.65 (d, J = 9.1 Hz, 1H); 8.41 (d, J = 5.2 Hz, 1H);
Acknowledgment
The authors thank Compagnia di San Paolo, Torino,
Italy, for financial support of the Italian Malaria Network.
References and notes
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1
3h: H NMR (CDCl3) d 1.24–1.56 (m, 5H); 1.74–1.96 (m, 5H); 2.62–
2.70 (m, 1H); 4.75 (s, 2H); 6.57 (d, J = 4.9 Hz, 1H); 7.52 (s, 1H); 7.55
(d, J = 1.8 Hz, 1H); 7.92 (d, J = 7.3 Hz, 1H); 8.47 (d, J = 4.9 Hz, 1H);
3i: 1H NMR (CDCl3) d 1.22–1.53 (m, 5H); 1.74–1.90 (m, 5H); 2.56 (s,
3H); 2.23 (s, 2H); 6.47 (s, 1H); 7.47 (s, 1H); 7.51 (d, J = 1.8 Hz, 1H);
7.84 (d, J = 8.8 Hz, 1H); 3j, 1H NMR (CDCl3) d 2.53 (s, 3H); 4.35 (s,
2H); 6.06 (s, 2H); 6.43 (s, 1H); 7.25 (s, 1H).
7. Elderfield, R. C.; Gensler, W. J.; Birstein, O.; Kreysa, F. J.; Maynard,
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