Some imines and azo compounds containing furoxan ring synthesized from methylisoeugenol

Article abstract of DOI:10.1002/jhet.5570430635

Some imines and azo compounds containing furoxan and benzene rings have been prepared starting from methylisoeugenol. The structure of reported compounds has been confirmed by elemental analysis, ms, uv, ir, and nmr spectroscopy. It is shown that, on trea

Full text of DOI:10.1002/jhet.5570430635

Nov-Dec 2006
1657
Some Imines and Azo Compounds
Containing Furoxan Ring Synthesized from Methylisoeugenol
Nguyen Huu Dinh*, Ngo Thi Ly, and Pham Van Hoan
Department of Chemistry, Hanoi University of Education
Hanoi, Vietnam
Received November 16, 2005
CH=CH-CH3
3 steps
H3CO
H3CO
N=N-Ar
CH3
N=CH-Ar
CH3
NH2
H3CO
H3CO
H3CO
H3CO
H3CO
H3CO
1) HNO2 2) ArH
0-5 oC
ArCH=O
- H2O
CH3
N
N
N
N
N
N
O
O
O
O
O
O
Some imines and azo compounds containing furoxan and benzene rings have been prepared starting
from methylisoeugenol. The structure of reported compounds has been confirmed by elemental analysis,
ms, uv, ir, and nmr spectroscopy. It is shown that, on treatment with Na2S2O4, the nitro group on the
benzene ring was reduced to an amino group, but the NꢀO group of furoxan ring was not. The 1H- and 13
C
nmr signals are assigned based on their spin-spin splitting patterns, in some cases, NOESY and HMBC
spectra are used. The NOESY spectra indicate that the reported imines have E-configuration. Among 8
tested compounds, there are 5 compounds that exhibit anti-microbial activity toward Gr+ S. aureus at
concentration 12.5μg /mL.
J. Heterocyclic Chem., 43, 1657 (2006).
Introduction.
prepared from 4-(3,4-dimethoxyphenyl)-3-methylfuroxan
as described in scheme I.
Furoxan derivatives display a variety of biological
activities, their vasodilator activity and inhibition of
platelet aggregation is well known [1,2,3]. Anti-
parasitic properties, mutagenic, anticancer effects,
anti-microbial, fulgicidal activities are listed [1,4].
These encouraged us to synthesize a few series of 4-
aryl-3-methylfuroxans with a moiety of essential oil
constituents and to find out if the resulting
Although compound 1 has been prepared by reaction of
methylisoeugenol with nitrous acid in 1894 year [7] nitro-
and amino compounds 2 and 3 up to now were not
described. The nitro compound 2 is obtained by nitration
of 1 (see experimental). In the 1H nmr spectrum of 1, there
4
are 3 signals of 3 aromatic protons: 7.30 (d, J = 2 Hz);
3
7.32 (dd, J=8, 4J=2 Hz); 7.16 (d, 3J=8 Hz). In the
spectrum of 2 there are 2 singlets at 7.89 and 7.39 ppm,
Scheme I
NO2
NH2
H3CO
H3CO
H3CO
H3CO
H3CO
H3CO
HNO3
Na2S2O4
CH3
CH3
CH3
N
N
N
N
N
O
N
O
O
O
O
O
(1)
(2)
(3)
corresponding to the 2 aromatic protons at the para-
position relative to one another. This indicates that, the
nitro group is introduced into the para- position relative to
the methoxy group (position 5, formula A).
compounds have any biological action. In previous
papers we reported on several imines and azo
compounds containing a furoxan ring derived from
anethole [5] and safrole [6]. Herein some analogous
compounds synthesized from methylisoeugenol are
described.
When 2 is treated with iron, tin, zinc or tin(ꢁꢁ)
chloride in the presence of hydrochloric or acetic
acids at 20 - 80 °C, we did not obtain the expected
amine, hence, the starting nitro compound is not
reduced under these conditions. Attempts to reduce 2
in toluene with sodium dithionite in alkaline medium
Results and Discussion.
A key intermediate for the title compounds, 4-(2-
amino-3,4-dimethoxyphenyl)-3-methylfuroxan (3), was

1658
N. H. Dinh, N. T. Ly, and P. V. Hoan
Vol 43
according to the reported procedure for its analogue
[6] was unsuccessful. When anisole (methyl phenyl
ether) was used as the solvent in place of toluene we
receive 3 in 40% yield. This is acceptable since the
furoxan ring was partially decomposed in strong
alkaline medium. The ir spectrum of 3 shows two
peaks at 3461 and 3359 cm-1 resulting from the N-H
stretch of primary amine. The resonance of the NH2-
group appears as a broad singlet at 5.34 ppm. The EI
ms spectrum of 3 shows its molecular weight is 251
(98.5%). These indicate that, when 2 is treated with
Na2S2O4, the nitro group on benzene ring is reduced
and the NꢀO group on the furoxan ring is not.
corresponding to the loss of an oxygen atom, [M-16]+., is
very weak, while the peak corresponding to the loss of
two NO molecules, [M-60]+., is intense. These primary
fragmentations are characterized for 3-methyl-4-
arylfuroxans (scheme IV).
The compound 1 absorbs at 294 nm, while nitro-,
amino-, and imine-derivatives (2, 3 and 4-11) have a band
in region near 338-358 nm (logꢁ 3.8-4.7). This red shift is
associated with the extension of conjugation in the
molecules 2-11 compared with 1. The azo compounds
have bands in the visible region 393-455 nm (logꢁ 3.9-
4.6) due to the azo chromophore.
The NMR data of the examined compounds were
most informative with respect to their structures. The
numeration of the examined compounds especially for
analysis of nmr spectra is shown as in formula A and B
(Scheme V).
The condensation of 3 with aromatic aldehydes was
carried out in boiling ethanol for 8-10 h with or without
acidic catalyst to give the imines 4-11 (scheme II).
Scheme II
Scheme V
NH2
N=CH
Ar
CH3
17
C
11-18
H3CO
H3CO
Ar
H3CO
H3CO
H
6
7
R11-18
10
CH3
5
1
H3CO
ArCH=O
- H2O
6
7
10
CH3
9
N
5
4
8
1
7'
H3CO
N
O
N
N
N
2
CH3
9
O
H3CO
O
4
8
O
(3)
(4-11)
3
7'
N
N
2
H3CO
O
3
N
N
O
(A)
(B)
Ar: 4-NO2C6H4 (4), 3-NO2C6H4 (5), 3,4-OCH2OC6H3 (6), 3-pyridyl
(7), 2-ClC6H4 (8), 4-ClC6H4 (9), 4-FC6H4 (10), 4-CH3OC6H4 (11).
The resonances of 3-H-10ꢂH are listed in Table 1, the
resonances of 12-H-17ꢂH are listed in Table 2. The
assignment of the proton signals is based on their spin-
spin splitting patterns, and in some cases, based also on
NOESY- and HMBC spectra. For example, the NOESY
spectrum of 9 (formula B, Ar = 4-ClC6H4) is presented in
Figure 1.
The singlet at 8.82 ppm has been assigned to 17-H,
its cross peak (a) shows that singlet at 7.27 ppm
corresponds to 6-H, thus the next singlet (7.17 ppm )
was assigned to 3-H. The cross peak (b) shows
doublet at 7.83 ppm corresponding to 12-H, thus the
next doublet (7.60 ppm) was assigned to 13-H. Since
6-H is adjacent to 7-H and 3-H is adjacent to 7'-H
(formula B), the cross peaks (c) and (d) allow one to
distinguish signals of 7-H and 7'-H. The cross peaks
between 17-H (-CH=N-) and 6-H in the NOESY
spectrum of 9 and of the other imines (formula B)
also demonstrate that the imine group (-N=CH-) has
E-configuration (formula B).
Diazotizing 3 following reaction with phenols affords
the azo compounds 12-15 (scheme III).
Scheme III
NH2
N=N-Ar
CH3
H3CO
H3CO
H3CO
H3CO
1) HNO2 2) ArH
0-5 oC
CH3
N
O
N
N
N
O
O
O
(3)
(12-15)
Ar: 3-CH3-4-HOC6H3 (12), 3-Cl-4-HOC6H3 (13), 2-NO2-4-HOC6H3
(14), 4-HOC6H4 (15).
The obtained imines are yellow crystals, and the azo
compounds are orange or red crystalline solids. The
structures of the compounds were confirmed by uv-, ir-,
ms- and nmr spectroscopy.
EI- ms data of the examined compounds agree with the
expected molecular weight (see experimental). The peak
Scheme IV
.
R
N
R
.
-
+
-
.
-
R
N
+
+
H3CO
H3CO
H3CO
H3CO
_
_
_
C-CH3
- O
CH3
-2NO
CH3
C
H3CO
H3CO
N
N
O
O
O
.
.
[M-60]+
[M]+.
[M-16]+

Nov-Dec 2006
Some Imines and Azo Compounds
1659
Table 1
Resonance signals from H-3-H-10 of examined compounds (formula A), ꢀ, ppm, J Hz.
Compd
3-H
6-H
7-H
7'-H
10-H
Other
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
7.30; d; 4J 2
7.39; s
6.81; s
7.20; s
7.20; s
7.18; s
7.18; s
7.20; s
7.17; s
7.18; s
7.15; s
7.30; s
7.33; s
7.339; s
7.30; s
7.16; d; 3J 8
7.89;.s
6.50; s
7.35; s
7.35; s
7.19; s
7.29; s
7.22; s
7.27; s
7.28; s
7.20; s
7.47; s
7.49; s
7.343; s
7.48; s
3.84; s
3.97; s
3.75; s
3.94; s
3.94; s
3.92; s
3.93; s
3.94; s
3.93; s
3.94; s
3.93; s
3.92; s
3.93; s
3.93; s
3.93; s
3.83; s
3.94; s
3.67; s
3.86; s
3.85; s
3.83; s
3.94; s
3.85; s
3.84; s
3.84; s
3.83; s
3.92; s
3.92; s
3.88; s
3.92; s
2.31; s
2.01; s
2.17; s
2.07; s
2.10; s
2.06; s
2.07; s
2.07; s
2.07; s
2.08; s
2.07; s
1.97; s
1.98; s
1.96; s
1.97; s
7.32; dd; 5-H
-
5.34; s; NH2
-
-
-
-
-
-
-
-
-
-
-
-
It is interesting that the NOESY spectrum of 1 yields
cross peaks between the methyl group (10-H) and either
of 3-H, 5-H. This demonstrates that the furoxan and the
benzene rings rapidly rotate on the nmr time scale or two
rings could not be coplanar.
Gasco and colleges [8] showed that the chemical shift
of a ring methyl group adjacent to the N-oxide oxygen of
furoxans occurs at 2.30-2.33 ppm, while a ring methyl
group remote from it, at 2.50-2.53 ppm. The signal of the
ring methyl group (10-H) of 1-15 appears as a singlet at
1.96-2.08 ppm (Table 1) indicating that the methyl group
is at position 3 of the furoxan ring.
The 13C NMR data are given in Tables 3 and 4. The
assignment of the 13C signals are based on their chemical
shift and HMBC spectra of the examined compounds (1,
Figure 1. NOESY spectrum of compound 9.
Figure 2. A part of HMBC spectrum of compound 5.

1660
N. H. Dinh, N. T. Ly, and P. V. Hoan
Vol 43
Table 2
Resonance signals from 12-H-17ꢀH of examined compounds (formula A), ꢁ,ppm, J Hz
No
R
12-H
13-H
8.37; d
3J 8.5
14-H
-
15-H
8.37; d
3J 8.5
16-H
8.06; d
3J 8.5
Others
8.99; s; 17-H
12
8.06; d
3J 8.5
13
-NO2
17
11
4
N=CH-
16
16
15
15
8.61; s
-
8.36; dt
7.82; t
3J 8
8.23; d
3J 8
9.01; s; 17-H
17 11
5
3J 8; 4J 1.5
14
-NO2
N=CH-
13
12
16
11
N=CH-
8.68; s; 17-H
6.12; s; 18-H
15
17
7.27; d
4J 1.5
7.07; d
3J 8
8.37; dd
3J8.5; 4J1.5; 4J1.5
6
7
8
-O
18
-
-
-
12
O
13
14 15
8.96; d
4J 1.5
8.16; d
3J 7.5
7.55; dd
3J 7.5; 5
8.69; dd
3J5; 4J 1.5
8.89; s; 17-H
17
13
16
11
N=CH-
N
12
16
15
17
N=CH1-1
7.59;dd
3J 8;4J 1
7.55; td
7.48;t
3J 8
7.92; dd
14
-
8.98; s; 17-H
8.82; s; 17-H
3J 8; 4J1.5
3J 8; 4J1.5
13
12
12
Cl
13
11
17
N=CH-
9
7.83; d
3J 8,5
7.60; d
3J 8,5
7.60; d
3J 8,5
7.83; d
3J 8,5
-Cl
-
-
16
15
12
13
14
17
N=CH-
11
7.88; dd;
3J 8.5; 4J 6 (a)
7.37; t;
3J 9 (b)
7.37; t
3J 9 (b)
7.88; dd
3J 8.5; 4J 6 (a)
8.81; s; 17-H
10
11
F
15
15
16
8.71; s; 17-H
3.83; s; 18-H
16
11
18
-OCH3
17
N=CH-
7.77;d
3J 8.5
7.08;d
3J 8.5
7.08;d
3J 8.5
7.77;d
3J 8.5
-
-
13
15
12
16
11
7.56; d
4J 2
6.94; d
3J 8.5
7.47;dd
3J 9;4J 2
2.19; s; 17-H
10.29; s; OH
12
13
14
15
-
-OH
17
N=N-
_
12
13 CH3
15
16
11.16; s; OH
11
N=N-
7.75;d
4J 2
7.15;d
3J 8.5
7.63;dd
3J8.5; 4J2
-OH
_
Cl
-
-
-
13
12
15
-OH
16
-
7.30;d
4J 2
7.59;d
3J 9
-
11
N=N-
7.16;dd
3J 9; 4J 2
_
O2N
12
13
16 15
11
10.35; s; OH
7.65;d
3J 8,5
6.93;d
3J 8,5
6.93;d
3J 8,5
7.65;d
3J 8,5
N=N-
-OH
13
12
2, 3, 4, 5, 7, 8, 9, 11, 12,13, 14, 15). For example, HMBC
spectrum of 5 (formula B, Ar = 3-O2NC6H4) is presented
in Figure 2.
12-C and 16-C; the cross peaks of 17-C (k, l ), in turn,
show signals of 12-H, 16-H; and so on.
Chemical shift of 1-C- 9ꢀC significantly changed from
1 to 2 and 3, but little changed from 4 to 15 (Table 3).
Two carbon atoms of the furoxan ring show a remarkably
large chemical shift difference in the 13C nmr: ꢀ
(8ꢀC) 157ꢀ158, ꢀ(9ꢀC) 113ꢀ114 ppm. Their assignment
is based on HMBC spectra: both 9-C and 8-C give cross
peaks with methyl protons 10-H but only 8-C forms cross
peak with 3-H (peak a, Figure 2). The N-oxide group
The signals of the protons 3-H, 6-H, 7-H, 10-H and 17-
H are always assigned unambiguously. The signals of ring
carbons are thus identified. For example, in Figure 2,
three cross peaks of 3-H (a, b, c) show signals of 8-C
(157.51), 1-C (151.44), 5-C (141.55); two cross peaks of
6-H (d, e) show signals of 2-C (148.33), 4-C (114.51); the
cross peaks of 17-H (f, g, h, i) show signals of 5-C, 11-C,

Nov-Dec 2006
Some Imines and Azo Compounds
1661
Table 3
Resonance signals from 1-C - 10-C of examined compounds (formula A), ꢀ, ppm.
Comp.
1-C
2-C
3-C
4-C
5-C
6-C
7-C
7'-C
8-C
9-C
10-C
1
2
3
151.11
153.34
152.24
151.72
151.71
151.78
151.71
151.70
151.79
151.76
151.52
151.71
152.36
151.53
149.13
150.34
140.18
148.55
148.33
148.16
148.08
147.90
147.81
147.35
151.14
151.51
151.42
151.26
110.43
114.06
113.74
112.71
112.68
112.69
112.70
112.62
112.70
112.61
112.40
112.46
112.63
112.43
118.54
114.29
99.90
120.78
140.23
142.57
141.61
141.55
142.08
142.36
142.11
142.40
142.85
143.68
143.40
143.53
143.62
111.99
108.46
100.19
102.14
102.19
102.19
102.40
102.15
102.24
102.10
98.29
55.67
56.77
55.22
55.98
55.96
56.00
55.93
55.89
55.95
55.84
56.10
56.20
56.27
56.12
55.67
56.46
56.40
56.00
55.96
56.00
55.93
55.89
55.95
55.34
55.69
55.78
55.63
55.72
157.06
156.43
157.02
157.52
157.51
157.65
157.44
157.62
157.74
157.88
157.36
157.07
156.69
157.30
112.91
113.70
113.60
114.19
114.11
114.25
113.82
114.01
113.88
114.22
114.30
114.28
114.12
114.32
9.01
7.57
9.07
8.77
8.80
8.84
8.72
8.76
8.83
8.84
8.52
8.50
8.37
8.49
4
114.85
114.51
114.28
114.02
114.15
114.22
113.46
118.66
119.41
120.11
118.89
5
7
8
9
10
11
12
13
14
15
98.33
98.34
98.24
exerts a shielding influence on 9-C and 10-C. Thus, the 9-
C appears upfield of the 8-C by 42-44 ppm. These data
4-15 as well as group -NH2 - for 6-C of 3. As
expected, for 4-11, the 13C of imine group (17-C)
Table 4
Resonance signals from 11-C - 18ꢁC of examined compounds, (formula A), ꢀ, ppm,J, Hz
(The numeration was shown in Table 2)
Com.
11-C
12-C
13-C
14-C
15-C
16-C
17-C
18-C
4
5
7
8
9
141.33
137.38
-
129.52
123.18
150.42
134.93
130.10
130.93 d
3JF,C 9.1
130.35
126.18
124.41
148.68
124.85
124.20
148.21
131.48
130.13
129.09
116.11 d
2JF,C 22
114.41
125.06
120.84
110.15
116.14
148.85
125.72
134.80
132.97
136.17
164.08 d
1JF,C 250
162.05
159.36
156.44
160.91
161.14
124.20
130.69
124.29
127.75
129.09
116.11 d
2JF,C 22
114.41
115.21
117.04
119.82
116.14
129.52
133.86
152.08
128.22
130.10
130.93 d
3JF,C 9.1
130.35
121.66
123.23
121.18
124.86
158.45
158.41
158.23
156.33
159.15
159.20
-
-
-
-
-
-
132.54
134.64
132.55 d
4JF,C 2.8
126.69
144.91
145.09
135.61
145.06
10
11
12
13
14
15
159.62
15.89
-
-
-
55.87
-
-
-
-
are in good agreement with those of references [10,11].
It is interesting that the imine- (-N=CH-) and azo-
(-N=N-) groups result in down-field shifts for 6-H of
4-15 as well as group -NO2 - for 6-H of 3 (Table 1),
but the same groups cause up-field shifts for 6-C of
resonated at the lowest field (Table 4).
The compounds 7, 8, 9, 11, 12, 13, 14, 15 are tested for
anti microbial activities. The results are listed in Table 5.
It is seen that the compounds 7, 8, 9, 11, and 14 showed
high activity toward Gr+ S.aureus.
Table 5
The minimum inhibition concentration (MIC) (μg/ml) of examined compounds against some microorganism.
Compd.
E.coli
B.subtillis
S.aureus
F.oxysprorum
C.albicans
7
8
9
11
12
13
14
15
25
50
50
12.5
50
100
-
-
25
-
12.5
12.5
12.5
12.5
25
100
12.5
50
-
-
-
50
-
-
-
-
100
-
12.5
50
-
100
25
-
-
100
-
-
-
-

1662
N. H. Dinh, N. T. Ly, and P. V. Hoan
Vol 43
EXPERIMENTAL
Anal. Calcd. for C11H13 N3O4: C, 52.59; H, 5.18; N, 16.73.
Found: C, 52.42; H, 4.89; N, 17.11.
IR spectra were recorded on a IMPACK- 410 NICOLET
spectrometer in KBr discs at 400-4000 cm-1. The uv spectra was
recorded in ethanol at concentration 10-4–10-5 M using uv-vis
Cintra spectrometer. The EI mass spectra of examined
compounds were recorded using 5989B Hewlett-Packard mass
spectrometer. Nmr spectra were recorded on Bruker AVANCE
500 MHz spectrometer, all at 298-300 K, in d6-DMSO with
TMS as the internal standard. The antimicrobial activities
toward E. coli, B. subtillis, S. aureus, F. oxysprorum, C.
albicans were tested at the Experimental biological Lab -
institute of Chemistry of natural compounds (in Hanoi), using
the method "Vande Bergher and Vietlink " [9].
General Procedure for the Preparation of Imines 4-11.
A solution of 1 mmol of 3 and 1 mmol of an aromatic
aldehyde dissolved in 20 mL of ethanol (for the preparation of 6,
9 and 11, 2 drops of acetic acid was also added) was refluxed
over 8-10 hours. Upon cooling the mixture to room temperature,
the resulting yellow precipitate was collected and recrystallized.
3-Methyl-4-[2-(4-nitrobenzylyden)amino-4,5-dimethoxyphenyl]-
furoxan (4).
This compound was obtained as yellow cristalline solid (from
ethanol); The yield 0.27 g (70%), mp 216-7 °C. ir (KBr): 3029,
2973 (C-H), 1600, 1528, 1514 (ring); uv (ethanol), ꢀmax,
nm/logꢁ: 345/4.7, 258/4.3, 207/4.2;x ms: m/z 323 (M+), 307
(M+-O), 293 (M+-NO), 263 (M+-2NO); 1H- and 13C nmr see
Table 1, 2, 3 and 4.
4-(3,4-Dimethoxyphenyl)-3-methylfuroxan (1).
Methylisoeugenol (17.8 g, 0.1 mol) was dissolved in 50 mL
of acetic acid. To this solution NaNO2 (15.1 g, 0.12 mol) was
added in portions over 4 hours and stirred at 25-30 °C for an
additional hour. The reaction mixture was poured into 100 mL
of water. The organic layer was separated, washed with water.
The residual was dissolved in 50 mL of hot ethanol and allowed
to cool to room temperature. The resulting yellow precipitate
was collected, recrystallized from ethanol and then from
benzene to give light yellow needle crystals. The yield 20.3 g
(86%), mp 118-119 °C (118 °C [1]). ir (KBr): 3088, 3013 (C-H),
1605, 1587 (ring); uv (ethanol), ꢀmax, nm/logꢁ: 294/3.8,
270/3.9, 208/4.2; ms: m/z 236(M+), 220(M+-O), 176(M+-2NO);
1H nmr and 13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C18H16 N4O6: C, 56.27; H, 4.16; N, 14.57.
Found: C, 55.92; H, 4.42; N, 14.18.
3-Methyl-4-[2-(3-nitrobenzylyden)amino-4,5-dimethoxyphenyl]-
furoxan (5).
Yellow needles (from ethanol); the yield 0.25 g (65%), mp
219-220°C. ir (KBr): 3086, 3021, 2967 (C-H), 1611, 1521
(ring); uv (ethanol), ꢀmax, nm/logꢁ: 355/3.8, 257/4.3, 240/4.3,
1
206/4.29 ; H- and 13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C18H16 N4O6: C, 56.27; H, 4.16; N, 14.57.
Found: C, 55.97; H, 3.83; N,14.72.
Anal. Calcd. for C11H12N2O4: C, 55.93; H, 5.08; N, 11.86.
Found: C, 55.84; H, 4.98; N, 11.55.
3-Methyl-4-[2-(3,4-methylendioxybenzylyden)amino-4,5-di-
methoxyphenyl]furoxan (6).
4-(4,5-Dimethoxy-2-nitrophenyl)-3-methylfuroxan (2).
Yellow needles (from ethanol); the yield 0.23 g (60%), mp
220°C. ir (KBr): 3108, 2972, (C-H), 1605,1530 (ring); uv
(ethanol), ꢀmax, nm/logꢁ: 350/4.1, 254/4.7,218/4.9 208/4.8; 1H-
and 13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C19H17 N3O6: C, 59.55; H, 4.44; N, 10.96.
Found: C, 59.25; H, 4.22; N, 10.83.
To a stirred solution of 11.8 g (0.05 mol) of 1 in 40 mL of acetic
acid, at room temperature was slowly added a mixture of HNO3
(12 mL, D = 1.41 g/mL) and H2SO4 (20 ml, D= 1.84 g/mL). The
reaction mixture was stirred at 50-60 °C for 3 hours. The reaction
mixture was allowed to cool to room temperature. The solid was
collected and washed with water, with Na2CO3 solution, and then
with water to neutralize. The resulting precipitate was recrystallized
from ethanol. The yellow needle crystals were dried in vacuum at 50
°C for 2 hours. The yield 9.8 g (70%), mp 162-3 °C. ir (KBr): 3086,
3006(C-H), 1616,1576 (ring); uv (ethanol), ꢀmax, nm/logꢁ: 338/3.8,
250/4.3, 200/4.4; ms: m/z 281(M+), 265(M+-O), 221(M+-2NO); 1H-
and 13C nmr see Table 1, 2, 3 and 4.
3-Methyl-4-[2-(3-pyridymethylyden)amino-4,5-dimethoxyphen-
yl]furoxan (7).
Yellow needles (from ethanol); The yield 0.30 g (90%), mp
213-4°C. ir (KBr): 3007, 2969, 22844 (C-H), 1611,1532 (ring);
uv (ethanol), ꢀmax, nm/logꢁ: 357/3.6, 258/3.9; 1H- and 13C nmr
see Table 1, 2, 3 and 4.
Anal. Calcd. for C17H16 N4O4: C, 60.02; H, 4.70; N, 16.47.
Found: C, 59.67; H, 4.67; N, 16.81.
Anal. Calcd. for C11H11N3O6: C, 46.97; H, 3.91; N, 14.94.
Found: C, 46.62; H,4.05; N, 15.16.
3-Methyl-4-[2-(2-chlorobenzylyden)amino-4,5-dimethoxyphen-
yl]furoxan (8).
4-(2-Amino-4,5-dimethoxyphenyl)-3-methylfuroxan (3).
To a vigorously stirred solution of 14.05 g (0.05 mol) of 2 in
150 mL of anisole, at 90°C was slowly added a solution of
Na2S2O4 (52.2 g, 0.3 mol) and NaOH (12 g, 0.3 mol). The
reaction mixture was stirred at 90°C for 2 hours additional. The
organic layer was extracted and allowed to cool to room
temperature. The resulting precipitate was collected, recrystal-
lized from ethanol and then from benzene to give light yellow
needle crystals. The yield 3.89 g (31%), mp 175-176°C. ir
(KBr): 3461, 3359, 1620 (NH2), 3017, 2996 (C-H), 1597, 1528
(ring); uv (ethanol), ꢀmax, nm/logꢁ: 346/3.3, 253/3.9, 207/4.3;
ms: m/z 251 (M+), 235(M+-O), 191 (M+-2NO); 1H- and 13C nmr
see Table 1, 2, 3 and 4.
Yellow needles (from ethanol); the yield 0.32 g (85%), mp
187-8 °C. ir (KBr): 3003, 2964, 2843, (C-H), 1604, 3164 (ring);
uv (ethanol), ꢀmax, nm/logꢁ: 356/4.1, 263/4.5, 208/4.6; 1H- and
13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C18H16 N3ClO4: C, 57.85; H, 4.28; N, 11.24.
Found: C, 57.72; H, 4.41; N, 11.54
3-Methyl-4-[2-(4-chlorobenzylyden)amino-4,5-dimethoxyphen-
yl]furoxan (9).
Yellow needles (from ethanol); the yield 0.33 g (89%), mp
184-5 °C. ir (KBr): 2994, 2947, 2844 (C-H), 1605, 1530, (ring);

Nov-Dec 2006
Some Imines and Azo Compounds
1663
uv (ethanol), ꢀmax, nm/logꢁ: 350/4.3, 267/4.6; 1H- and 13C nmr
see Table 1, 2, 3 and 4.
ꢀmax, nm/logꢁ: 425/shoulder, 393/4.6, 260/4.7, 200/4.8; 1H-
and 13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C18H16 N3ClO4: C, 57.85; H, 4.28; N, 11.24.
Found: C, 57.69; H, 3.96; N, 11.60
Anal. Calcd. for C17H15N4O5Cl: C, 52.28; H, 3.84; N, 14.34.
Found: C, 51.95; H, 3.92; N, 14.67
3-Methyl-4-[2-(2-nitro-4-hydroxyphenyl)diazenyl-4,5-dimeth-
oxyphenyl]furoxan (14).
3-Methyl-4-[2-(4-florobenzylyden)amino-4,5-dimethoxyphen-
yl]furoxan (10).
This compound was obtained as light red crystalline solid
(from dioxane); the yield 0.25 g (62%), mp 221-3 °C. ir (KBr):
3441 (OH), 3092, 2951, 2843 (C-H), 1606, 1529 (ring); uv
(ethanol), ꢀmax, nm/logꢁ: 455/shoulder, 398/3.8, 263/4.0,
This compound was obtained as light-yellow needles (from
ethanol); The yield 0.27 g (75%), mp 178-9°C. ir (KBr): 3017,
2945, 2845 (C-H), 1621, 1598, 1525 (ring); uv (ethanol), ꢀmax,
nm/logꢁ: 348/3.9, 258/4.1, 213/4.2; 1H- and 13C nmr see Table 1,
2, 3 and 4.
1
205/4.5; H- and 13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C17H15N5O7: C, 50.87; H, 3.74; N, 17.45.
Found: C, 51.16; H, 3.57; N, 17.67
Anal. Calcd. for C18H16N3FO4: C, 60.50; H, 4.48; N, 11.76.
Found: C, 60.78; H, 4.31; N, 11.97
3-Methyl-4-[2-(4-hydroxyphenyl)diazeny)-4,5-dimethoxyphen-
yl]furoxan (15).
3-Methyl-4-[2-(4-methoxybenzylyden)amino-4,5-dimethoxy-
phenyl]furoxan (11).
This compound was obtained as orange crystalline solid (from
ethanol); the yield 0.30 g (83%), mp 209-210 °C. ir (KBr):
3451(OH), 3105, 3062, 2951 (C-H), 1600, 1529 (ring); uv
(ethanol), ꢀmax, nm/logꢁ: 425/shoulder, 392/4.4, 255/4.3; 1H-
and 13C nmr see Table 1, 2, 3 and 4.
Yellow needles (from ethanol); The yield 0.30 g (81%), mp
179-180°C. ir (KBr): 3004, 2955, 2857(C-H), 1605, 1569, 1530,
(ring); uv (ethanol), ꢀmax, nm/logꢁ: 345/4.2, 280/4.3, 235/4.27;
1H- and 13C nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C19H19N3O5: C, 61.79; H, 5.15; N, 11.38.
Found: C, 61.65; H, 5.05; N, 11.68
Anal. Calcd. for C17H16N4O5: C, 57.30; H, 4.49; N, 15.73.
Found: C, 57.66; H, 4.61; N, 15.45.
General Procedure for the Preparation of Azo Compounds
12-15.
REFERENCES
At 0-5 °C, 1.5 mL of 1 M NaNO2 solution was slowly added
to a solution of 1 mmol of 3 in 1 mL of 3 M HCl solution. The
resulting solution was slowly added to a solution of 1 mmol of a
phenol in 3 ml of 1.5 M NaOH solution. The mixture was
neutralized with diluted HCl solution. The precipitate was
collected and recrystallized.
[1] Hugo Cerecetto and Williams Porcal; Mini-Reviews in
Medicinal Chemistry, 5, 57-71 (2005).
[2] R. Ferioli, G. C. Polco, C. Ferretti, A. M. Gasco, C. Medana,
R. Fruttero, M. Civelli and A. Gasco, British Journal of Pharmacology,
114, 816-820 (1995).
[3] S. V. Pirogov, S. F. Mel’nikova, I. V. Zelinskii, T. V.
Romanova, N. P. Spiridonova, N. A. Medvedeva, T. V. Bulartina, Russ.
Patent RU 2240321 C2 20 Nov 2004; Chem. Abstr., 141, 395564.
[4] Kwang-Jin Hwang, Young C. Park, Hyung Jin Kim and Jae
Hyun Lee, Biosci. Biotechnol. Biochem., 62 (9), 1693-1697 (1998).
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Chemistry (of Vietnam, in English), 43, 128-132 (2005).
[6] Nguyen Huu Dinh, Ngo Thi Ly, Le Thi Thanh Van. J.
Heterocyclic Chem., 41, 1015-1021 (2004).
3-Methyl-4-[2-(3-methyl-4-hydroxyphenyl)diazenyl-4,5-dimeth-
oxyphenyl]furoxan (12).
This compound was obtained as orange needles (from etanol);
the yield 0.29 g (79%), mp 205-6 °C. ir (KBr): 3400 (OH), 3100,
3040, 2950, 2860 (C-H), 1593, 1521 (ring); uv (ethanol), ꢀmax,
1
nm/logꢁ: 425/shoulder, 394/4.3, 257/4.2, 207/4.1; H- and 13C
nmr see Table 1, 2, 3 and 4.
Anal. Calcd. for C18H18N4O5: C, 58.38; H, 4.86; N, 15.13.
Found: C, 58.67; H, 4.61; N, 15.39
[7] G. Malagnini, Gazz. Chim. Ital., 24, 1-20, (1894).
[8] A. Gasco, G. R. Mortarini and E. Menziani, J. Heterocyclic
Chem., 9, 837-841 (1972).
[9] K. Likhitwitayawuid, C. K. Angerhosr, G. A. Cordell, J. M.
Tezzuto, J. Natural Product, 56, 30-36 (1993).
[10] F. A. L. Anet and I. Yavari, Org. Magn. Reson., 8, 158
(1976).
[11] L. Stefaniak, M. Witanowski and G. A. Webb, Bull. Acad.
Pol. Sci., Ser. Sci. Chim., 26, 281 (1978).
3-Methyl-4-[2-(3-chloro-4-hydroxyphenyl)diazenyl-4,5-dimeth-
oxyphenyl]furoxan (13).
This compound was obtained as yellow crystalline solid (from
etanol); the yield 0.28 g (72%), mp 119-221°C. ir (KBr): 3439
(OH), 3090, 2943, 2844 (C-H), 1606, 1527, (ring); uv (ethanol),