Reactions of 4-nitroquinoline 1-oxide with aluminum chloride

Article abstract of DOI:10.1023/A:1012302206922

4-Nitroquinoline 1-oxide reacts with aluminum chloride to give 4-chloroquinoline 1-oxide. Aluminum chloride with 4-nitroquinoline 1-oxide forms a molecular complex in which it acts as electron acceptor and effective nucleophilic reagent (a source of chloride ions).

Full text of DOI:10.1023/A:1012302206922

Russian Journal of Organic Chemistry, Vol. 37, No. 1, 2001, pp. 141 143. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 1, 2001,
pp. 148 150.
Original Russian Text Copyright
2001 by Andreev, Nizhnik.
Reactions of 4-Nitroquinoline 1-Oxide
with Aluminum Chloride
V. P. Andreev and Ya. P. Nizhnik
Petrozavodsk State University, pr. Lenina 33, Petrozavodsk, 185640 Russia
e-mail: andreev@mainpgu.karelia.ru
Received September 3, 1999
Abstract 4-Nitroquinoline 1-oxide reacts with aluminum chloride to give 4-chloroquinoline 1-oxide.
Aluminum chloride with 4-nitroquinoline 1-oxide forms a molecular complex in which it acts as electron
acceptor and effective nucleophilic reagent (a source of chloride ions).
Halogenated pyridine and quinoline N-oxides are
key intermediate products in the synthesis of func-
tionally substituted heteroaromatic compounds; they
are usually prepared from the corresponding nitro
compounds under severe conditions: by prolonged
boiling in concentrated aqueous solutions of HCl and
HBr or by the action of acid halides and phosphinoyl
halides [1].
of chloride ions. According to the HPLC data, heating
of equimolar amounts of 4-nitroquinoline 1-oxide (I)
and AlCl in acetonitrile for 15 min at 65 C or
3
keeping of the reactant mixture for 24 h at room
temperature leads to formation of 4-chloroquinoline
1-oxide (II) in quantitative yield.
Addition of an equimolar amount of benzyltriethyl-
ammonium chloride (see table, runs. nos. 12 and 14)
almost does not affect the reaction rate, indicating
We showed in [2] that passing of gaseous hydrogen
chloride or hydrogen bromide through a saturated
solution of 4-nitroquinoline 1-oxide (I) in chloroform
over a period of 15 30 min leads to quantitative
replacement of the nitro group by halogen. The mild
conditions of this reaction are explained by protona-
tion of the N-oxide oxygen atom and increased
nucleophilicity of halide ions due to their weak solva-
tion by aprotic solvent.
that under these conditions anhydrous AlCl is at least
3
equally efficient source of chloride ions.
Unlike AlCl , such halogen-containing Lewis acids
3
as SbF , BF , ZnCl , and CuCl turned out to be
3
3
2
2
either poor halide ion sources (BF ) or poor electron
3
acceptors (ZnCl and CuCl ) or both (SbF ). Even
2
2
3
the use of AlCl 6H O ensures faster replacement
3
2
of the nitro group. The reaction was considerably
accelerated by preliminary addition to N-oxide I of
boron trifluoride (runs nos. 15 and 16) which is
a stronger electron acceptor that anhydrous aluminum
chloride (cf. runs nos. 7 and 14). By contrast, the
presence of protogenic species capable for specific
interactions inhibits the process. This pattern is
observed, e.g., in going from acetonitrile to methanol
In continuation of studies in this line, we tried to
activate the nitro group in heteroaromatic N-oxides
for nucleophilic substitution with the aid of anhydrous
aluminum chloride. The latter is known to form mole-
cular complexes with N-oxides [3], in which the
heteroring should exhibit enhanced electrophilicity
toward weak nucleophilic reagents. However, AlCl3
was found to act not only as powerful v-acceptor but
also as effective nucleophilic reagent being a source
(
runs nos. 1 and 2), from AlCl to AlCl 6H O (runs
3 3 2
nos. 1 and 15, 16 and 17, 21 and 22), from BF to
3
CF COOH or HClO (runs nos. 6 and 19, 20, 16 and
3
4
1
8). The same effect is observed with the use of
hydrogen chloride. The reaction with gaseous HCl in
chloroform is complete in 15 min at room tempera-
ture; in acetonitrile containing hydrochloric acid it
requires 24 h (run no. 24) or 30 min at 65 C (run
no. 23); and in 36% hydrochloric acid, despite greater
concentration of HCl, the reaction takes 1 h at 100 C.
1
070-4280/01/3701-0141$25.00 2001 MAIK Nauka/Interperiodica

1
42
ANDREEV, NIZHNIK
Substitution of the nitro group in 4-quinoline 1-oxide by chlorinea
Yield of 4-chloroquinoline 1-oxide (II), %
Run
no.
Temperature,
C
Components
3
0 min
>99
60 min
120 min
180 min
240 min
1
2
3
4
AlCl3
65
65
65
54
(5 min
70%, 15 min
57
98%)
AlCl3 (methanol)
ZnCl2
37
2
48
65
<1
10
CuCl2
5
7
(
8 ch
18%)
5
6
7
8
9
BF3
65
65
20
20
20
20
20
0
0
+
[Et NCH Ph] Cl BF
>99
80
3
2
3
3
+
[Et NCH Ph] Cl BF
99
45
3
2
SbF3
+
[Et NCH Ph] Cl SbF
3
3
2
3
+
1
1
0
1
[Et NCH Ph] Cl ZnCl
(24 h
55
0%)
3
2
2
b
AlCl3
60
88%, 19 h
47
96%, 19 h
8
65
56
12
1
1
0 h
0 h
80%, 14 h
23 40
86%, 14 h
90%
98%
1
1
2
3
AlCl3c
20
20
AlCl d
1
5
3
(
19 h
(24 h
20
45%)
99%)
+
1
1
4
5
[Et NCH Ph] Cl AlCl
3
20
65
25
<1
3
2
AlCl H O
31
56
3
2
(
60
>99
10 h
83%, 16 h
65
86%)
96
d
16
17
18
19
20
21
22
23
24
25
AlCl H O BF
3
65
65
51
>99
90%)
>99
95
3
2
d
AlCl BF
(5 min
64%, 15 min
3
3
AlCl H O CF COOH
65
65
65
65
65
65
20
100
12
80
75
<1
82
45
90
80
7
83
93
3
2
3
+
[Et NCH Ph] Cl CF COOH
[Et NCH Ph] Cl HClO
70
65
3
2
3
+
3
2
4
+
AlCl H O [Et NCH Ph] Cl
3
2
3
2
d
AlCl3 (NC) C C(NC)
2
2
Concd. hydrochloric acid
Concd. hydrochloric acid
Concd. hydrochloric acid
>99
50
65
>99
(24 h
(15 min
>99%)
65%)
a
In a typical experiment, the reaction mixture contained 0.3 ml of anhydrous acetonitrile (except for runs nos. 2 and 25), 0.1 mmol
of 4-nitroquinoline 1-oxide (I), 0.1 mmol of nucleophile, and 0.02 ml of a solution of boron trifluoride ether complex, concentrated
solutions of trifluoroacetic, perchloric, or hydrochloric acid or 0.1 mmol of solid SbF , AlCl , ZnCl , or CuCl as electron acceptor.
3
3
2
2
b
c
d
e
Molar ratio N-oxide (I) AlCl3 2:1.
Molar ratio N-oxide (I) AlCl3 1:1.
Molar ratio N-oxide (I) AlCl3 1:2.
Boron trifluoride or tetracyanoethylene was added to the reaction mixture before addition of AlCl3.
We have also found that changing the ratio N-oxide
quinoline N-oxides [4] and their styryl derivatives
I AlCl from 2:1 to 1:2 slows the reaction down.
with [5] with BF were isolated in the pure state.
3
3
Obviously, in this case the fraction of complex IV
relative to III should increase. Complex IV is
characterized by greater deficit of electron density on
the aluminum atom (sextet of electrons) due to com-
Presumably, nucleophilic substitution of the nitro
group in N-oxide by the action of AlCl or hydrogen
3
halides (HCl, HBr) involves formation of a molecular
complex of I with Lewis or Br o/ nsted Lowry acid,
liberation of halide ion, and attack by the latter on
the aromatic ring. It should be noted that proton is
such a strong electron acceptor that 4-nitroquinoline
petition between two AlCl molecules; therefore,
3
generation of nucleophilic species (chloride ion) from
complex III is more favorable. Similar adducts of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001

REACTIONS OF 4-NITROQUINOLINE 1-OXIDE
143
in 3 ml of dry acetonitrile was heated for 15 min at
5 C. The progress of the reaction was monitored by
6
TLC and HPLC [2]. The solvent was distilled off, and
the solid residue was treated with 2 ml of a saturated
aqueous solution of NaCO and with chloroform
3
(
3 2 ml), and the chloroform extract was dried over
MgSO . The solvent was removed under reduced
4
pressure to obtain 0.145 g (81%) of compound II with
1
-oxide hydrochloride cannot be isolated in the pure
mp 132 134 C (mp 133 133.5 C [10]). Its UV, IR,
state (by analogy with the I AlCl complex) because
of very fast replacement of the nitro group by
chlorine. On the other hand, the complex of I with
BF is fairly stable (complex formation involves the
nitro group [4]. Complex formation of other N-oxides
with HCl and BF occurs at the oxygen atom of the
N-oxide group, except for 4-(4-dimethylaminostyryl)-
quinoline N-oxide and 4-(4-dimethylaminostyryl)-
pyridine N-oxide which take up the second BF3
molecule or proton at the amino group.
Apart from n-donors, typical v-acceptors are also
capable of forming ,v-complexes. For example,
AlCl and GaCl [6], as well as HCl [7], form com-
1
3
and H NMR spectral data coincided with those of
a sample prepared by the procedure reported in [1].
Found, %: C 59.65, 59.95; H 3.43, 3.77; N 7.71, 7.52.
C H ClNO. Calculated, %: C 60.19; H 3.37; N 7.80.
3
9
6
4
-Chloroquinoline 1-oxide hydrochloride was obtained
3
as described in [2]; its melting point (151 152 C) and
UV spectrum coincided with the data given in [2].
b. A mixture of 0.380 g of N-oxide I and 0.134 g
of anhydrous AlCl in 6 ml of dry acetonitrile was
3
kept for 24 h at room temperature. The product was
isolated as described above in a. Yield 0.301 g (84%).
3
3
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1
2
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.
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.
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1
KBr. The H NMR spectra were obtained on a Bruker-
3
00 spectrometer using CDCl as solvent and TMS
3
as internal reference.
-Chloroquinoline 1-oxide (II). a. A mixture of
.19 g of N-oxide I and 0.067 g of anhydrous AlCl3
4
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0
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001