Reactions of 4-aryl-2-hydrazino-3-nitro-6-R-quinolines with HNO2

Article abstract of DOI:10.1023/A:1023966827299

The reaction of 4-aryl-2-hydrazino-3-nitro-6-R-quinolines with NaNO₂ in AcOH gives the corresponding tetrazolo[1,5-a]quinolines. In contrast to tetrazolo[1,5-c]pyrimidines they cannot be converted to 6-R-4-phenyl[1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides by heating in THF, toluene, or AcOH. Total energy quantum-chemical calculations using the MTNDO/3 and MNDO methods show that [1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides are significantly higher in energy (230-280 kcal/mol) than the mentioned tetrazolo[1, 5-a]quinolines and hence their formation is unlikely.

Full text of DOI:10.1023/A:1023966827299

Chemistry of Heterocyclic Compounds, Vol. 39, No. 3, 2003
REACTIONS OF 4-ARYL-2-HYDRAZINO-
3-NITRO-6-R-QUINOLINES WITH HNO2
L. V. Grishchuk, E. I. Ivanov, V. E. Kuz'min, A. M. Turyanskaya, and R. Yu. Ivanova
The reaction of 4-aryl-2-hydrazino-3-nitro-6-R-quinolines with NaNO2 in AcOH gives the
corresponding tetrazolo[1,5-a]quinolines. In contrast to tetrazolo[1,5-c]pyrimidines they cannot be
converted to 6-R-4-phenyl[1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides by heating in THF, toluene, or
AcOH. Total energy quantum-chemical calculations using the MINDO/3 and MNDO methods show that
[1,2,5]oxadiazolo[3,4-b]quinoline-3-oxides are significantly higher in energy (230-280 kcal/mol) than
the mentioned tetrazolo[1,5-a]quinolines and hence their formation is unlikely.
Keywords: hydrazinoquinolines, oxadiazoloquinolines, tetrazoloquinolines, quinolines, ring-chain
(azido-tetrazole) tautomerism.
We have previously reported the synthesis of 4-aryl-2-hydroxy-3-nitro-6-R-quinolines 1, 2 (compounds
3, 4 were obtained under analogous conditions during the course of this work) [1]. The aim of this study is the
preparation of 2-chloro derivatives 5-8 of the previously reported compounds, 2-hydrazino-substituted
quinolines 9-11 derived from them, and also to study the reaction products of compounds 9-11 with nitrous acid.
The presence of an azide group and a nitro group in azides of type 12-14 can govern the formation of not only
the corresponding tetrazolo[1,5-a]quinolines 15-17 [2] but also [1,2,5]oxadiazolo[3,4-b]quinolines 18-20 [3].
N
OH
N
Cl
N
NHNH2
NO2
POCl3 / PCl5
POCl3
NHNH2
R
NO2
R
NO2
R
Ar
1–4
Ar
5–8
Ar
9–11
HNO2
N
N
N
N
N
N
N3
N
O
N
– N2
R
R
NO2
R
NO2
Ar
18–20
Ar
12–14
Ar
15–17
O
1, 5, 9, 15 R = Cl, Ar = Ph; 2, 6, 10, 16 R = Br, Ar = Ph; 3, 7 R = Br, Ar = 2-ClC6H4;
4, 8, 11, 17 R = NO2, Ar = Ph
__________________________________________________________________________________________
A. V. Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine, Odessa 65080;
e-mail: grishchuk@ukr.net. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 384-388,
March, 2003. Original article submitted February 20, 2001.
340
0009-3122/03/3903-0340$25.00©2003 Plenum Publishing Corporation

The conversion of compounds 1-4 to the halogenated products 5-8 was achieved by refluxing the
starting derivatives either with an excess of POCl3 or in a mixture of PCl5 and POCl3. The hydrazinolysis of
these 2-chloroquinolines was carried out using an excess of hydrazine hydrate in refluxing ethanol or in DMSO
at room temperature.
It was found that the reaction of hydrazines 9-11 with HNO2 occurs almost instantaneously to give
tetrazoloquinolines 15-17 but, in contrast to data in [3], prolonged refluxing the latter in glacial acetic acid,
toluene, or THF did not lead to the formation of compounds 18-20. The formation of structures related to 18-20
was possible only on prolonged heating of o-nitroaryl(heteryl)azides in the appropriate organic solvent medium
→
either directly [4] or via the realization of a ring-chain tautomerism of the type 15-17
12-14 [5].
←
The fact that the expected furoxans 18-20 were not formed in this way points to the absence of such a
tautomeric equilibrium at room temperature. This is also indicated by the absence of azide group stretching
bands at 2120 cm-1 in the IR spectra of compounds 15-17, both in the crystalline state and in CHCl3 or CCl4
solution [6].
In order to explain these facts we have carried out total energy quantum-chemical calculations for
compounds 12-20, the products of reaction of hydrazines 9-11 with nitrous acid. The semiempirical MINDO/3
and MNDO methods were used since it is known that they are fully suited for evaluation of the geometry and
the energy of organic molecules containing polar groups (NO2 in particular). The total energy calculations with
geometry optimization were carried out using the "HyperChem 6.0" program*. The energy of furoxano[3,4-b]-
quinolines 18-20 was found to be significantly (230-280 kcal/mol) higher than of all of the remaining products,
and this is why the formation of compounds 18-20 is unlikely. The calculated results (Table 1) show that the
energy of tetrazoles is lower than that of the corresponding azides. This is especially marked in the MNDO
method calculations. It is of interest to note that the nature of the substituent R has virtually no effect on the
energy difference (∆E). Hence, in all likelihood, thermodynamic grounds are the deciding factor in the
formation of tetrazoles 15-17 as the sole products of the reaction of hydrazines with nitrous acid.
Data of quantum-chemical calculation reflect the energy of the molecules in vacuo and do not take into
consideration the effect of the medium. In our view it is unlikely that solvation effects have a decisive influence
in the reaction discussed and so the qualitative conclusions made from the quantum-chemical calculations are
the most plausible.
TABLE 1. Calculated Total Energy Values (kcal/mol) for Compounds 12-20
Calculation
method
-E2
R
-E1 (azides)
-E3 (furoxans)
∆E = E1 – E2
∆E ' = E2 – E3
(tetrazoles)
H
MINDO/3
MNDO
MINDO/3
MNDO
3686
3561
3670
3545
3523
3886
3725
3692
3580
3676
3563
3541
3891
3742
3407
3347
3391
3330
3308
3606
3510
6
19
6
285
233
285
233
233
285
232
Cl
Br*
18
18
5
MNDO
NO2 MINDO/3
MNDO
17
_______
* Calculation by the MINDO/3 method was not carried out because of the
absence of parameters for the Br atom.
_______
* A fully working "trial" version of "HyperChem 6.0" is available from the Internet site of the HyperCube
company: www.hyper.com.
341

TABLE 2. Characteristics for the Synthesized Compounds
Found, %
——————
Com-
Empirical
formula
IR spectrum, ν, cm-1, KBr*2
М+
Yield, %
Calculated, %
mp, °С*
pound
C
H
Hal
N
C15H8BrClN2О3
C15H9N3O5
47.50
47.46
2.18
2.12
30.34
30.39
7.33
7.38
320-322
357-359
171-172
149-150
185-186
219-221
202-204
205-207
208-210
239-241
1380, 1520, 1610, 1660, 2900-3550
1325, 1515, 1600, 1660, 2800-3200
1380, 1515, 1640, 1670, 2800-3080
1370, 1520, 1640, 1660, 2800-3000
1380, 1520, 1640, 1650, 2860-3075
1330, 1515, 1600, 1645, 2780-3050
1375, 1520, 1580, 1620, 2800-3200, 3320
1340, 1520, 1590, 1620, 3050-3280, 3400
1320, 1520, 1560, 1590, 3000-3290, 3300
378
311
318
362
396
329
314
358
325
325
21
30.7
65
3
57.84
2.96
13.55
4
57.88
2.91
13.50
C15H8Cl2N2O2
C15H8BrClN2O2
C15H7BrCl2N2O2
C15H8ClN3O4
C15H11ClN4O2
C15H11BrN4O2
C15H11N5O4
56.40
56.45
2.48
2.53
22.27
22.22
8.82
8.78
5
49.59
2.25
31.68
7.75
68
6
49.55
2.22
31.73
7.70
45.31
45.26
1.81
1.77
37.93
37.88
7.00
7.04
96
7
54.70
2.50
10.80
12.77
50
8
54.65
2.45
10.75
12.74
57.28
57.24
3.56
3.52
11.21
11.26
17.22
17.18
51
9
50.11
3.13
22.30
15.55
88
10
11
15
50.16
3.09
22.25
15.60
55.44
55.39
3.46
3.41
21.49
21.53
96
C15H8ClN5O2
55.36
2.43
10.93
10.92
21.46
1040, 1060, 1360, 1520, 1610, 1640, 3050
(1020, 1080, 1355, 1540, 1610, 1680, 3080)
46.3
55.31
2.48
21.50
C15H8BrN5O2
C15H8N6O4
48.62
48.67
2.22
2.18
21.54
18.87
18.92
239-241
239-241
1040, 1070, 1365, 1520, 1590, 1640, 3055
369
336
97.6
45.2
16
17
21.59
(1020, 1080, 1355, 1540, 1610, 1680, 3080)
53.52
2.44
24.95
1020, 1080, 1320, 1530, 1600, 1680, 3055
53.58
2.40
24.99
_______
* Solvents were: ethanol (compounds 3-6,15) and benzene–heptane (compound 8).
*2 Values obtained in CHCl3 are given in brackets for compounds 15 and 16.

EXPERIMENTAL
IR spectra were recorded on a Specord M-80 instrument. Monitoring of the reaction course and the
purity of the compounds obtained was carried out using TLC on Silufol UV-254 plates with acetone–hexane
(1:2, 1:3, 1:4) as eluent. Mass spectra were taken on an MX-1321 mass spectrometer using a direct introduction
system and irradiation ionization energy of 70 eV.
Physicochemical constants for the compounds prepared are given in Table 2.
6-Bromo-4-(2-chlorophenyl)-2-hydroxy-3-nitroquinoline (3) and 2-Hydroxy-3,6-dinitro-4-phenyl-
quinoline (4) were prepared as in method [1].
2,6-Dichloro-3-nitro-4-phenylquinoline (5), 6-Bromo-2-chloro-3-nitro-4-phenylquinoline (6),
6-Bromo-2-chloro-4-(2-chlorophenyl)-3-nitroquinoline (7), and 2-Chloro-3,6-dinitro-4-phenylquinoline
(8). (General Method). Mixture of the corresponding quinoline 1-4 (8.5 mmol) with the equivalent amount of
PCl5 was refluxed in POCl3 (30 ml) to complete disappearance of the chromatographic spot for the starting
quinoline (28-50 h). After the conclusion of the reaction the mixture was poured into ice. The precipitate formed
was filtered off and washed with water. After drying, the precipitate was crystallized.
6-Chloro-2-hydrazino-3-nitro-4-phenylquinoline (9), 6-Bromo-2-hydrazino-3-nitro-4-phenyl-
quinoline (10), and 2-Hydrazino-3,6-dinitro-4-phenylquinoline (11). (General Method). A. Mixture of the
corresponding 2-chloroquinoline 5-8 (3.1 mmol) and 95% hydrazine hydrate (2 ml) was refluxed for 2 h in
ethanol (50 ml). The precipitate formed was filtered off, washed with alcohol, and dried.
B. 95% N2H4·H2O (2 ml) was added to the corresponding chloride 5-8 (3.1 mmol) in DMSO (40 ml).
The mixture was held for 3 h at room temperature and then poured into water. The precipitate formed was
filtered off, washed with slightly acidified water, and dried.
A mixed sample of the materials obtained using methods A and B did not give a depression of melting
point.
9-Chloro-6-nitro-7-phenyltetrazolo[1,5-a]quinoline
(15),
9-Bromo-6-nitro-7-phenyltetrazolo-
[1,5-a]quinoline (16), and 6,9-Dinitro-7-phenyltetrazolo[1,5-a]quinoline (17). (General Method). Saturated
aqueous solution of NaNO2 (6.8 mmol) was poured into solution of the corresponding 2-hydrazinoquinoline
(1.3 mmol) in AcOH (20 ml). The reaction mixture was stirred for 10 min. The precipitate formed was filtered,
washed with slightly acidified water, dried, and crystallized from ethanol.
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343