Synthesis of 5-nitropyridin-2-ylazo push-pull derivatives

Article abstract of DOI:10.1007/s10593-008-0013-9

A practical method has been devised for the synthesis of previously unknown push-pull azochromophores with 5-nitropyridin-2-yl acceptor moiety from 2-amino-5-nitro-1-oxypyridine.

Full text of DOI:10.1007/s10593-008-0013-9

Chemistry of Heterocyclic Compounds, Vol. 44, No. 1, 2008
SYNTHESIS OF 5-NITROPYRIDIN-
2-YLAZO PUSH-PULL DERIVATIVES
J. Kreicberga, E. Jecs, and V. Kampars
A practical method has been devised for the synthesis of previously unknown push-pull
azochromophores with 5-nitropyridin-2-yl acceptor moiety from 2-amino-5-nitro-1-oxypyridine.
Keywords: azo compounds, chromophore, pyridine.
Azo compounds with electron-donating substituents on one side of the molecule and electron-
withdrawing groups on the other side, or the so-called push-pull chromophores, are of lasting interest in the field
of nonlinear optical materials [1]. Recently, increasing interest has been paid to heterocycle-based push-pull
chromophores [2]. Incorporation of π-deficient pyridine conserves the photoactivity of azobenzene and
additionally provides the capability of self-assembly through H-bonding or metal coordination [3]. Although a
number of investigations have been reported in the literature on pyridin-4-ylazo dyes [3-6], only a few pyridin-
2-ylazo dyes have been synthesized [7, 8], and to our knowledge no reports exist on 5-nitropyridin-2-yl-azo push-
pull chromophore.
The aim of the present study was to synthesize 5-nitropyridin-2-ylazobenzene derivatives 1a-c bearing in
the electron-releasing part of the molecule a diethanolamino group [N(CH2CH2OH)2] and an octyloxy group that
efficiently, as our previous research shows [9], improve solubility and are expected to avoid the formation of
undesirable centrosymmetric structures in the solid state.
R
O2N
N
CH2CH2OH
CH2CH2OH
N
N
N
1a–c
a R = H, b R = OMe, c R = OC8H17
The usual diazotization-coupling reaction could not be used because of the impossibility to obtain the
diazonium salt from 5-nitropyridin-2-ylamine [7]. Three other methods for the synthesis of pyridin-2-ylazo
compounds are available: (1) the reaction of pyridin-2-amine with nitrosobenzene in the presence of a strong
base (50% NaOH, Bu4NOH) [10], (2) oxidation of pyridin-2-ylphenylhydrazine [11], and (3) condensation of
2-nitrosopyridine with substituted anilines catalyzed by AcOH [12]. The first two methods were not satisfactory
for our purposes owing to the instability of 2-amino-5-nitropyridine (2) in concentrated NaOH solutions and
__________________________________________________________________________________________
Riga Technical University, Faculty of Material Science and Applied Chemistry, Riga LV-1048, Latvia;
e-mail: jana@ktf.rtu.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 35-41, January,
2007. Original article submitted November 1, 2006.
0009-3122/08/4401-0029©2008 Springer Science+Business Media, Inc.
29

because feasible substituents in the phenyl moiety of hydrazine molecule were limited merely to electron
acceptors. To apply the third method, 2-nitroso-5-nitropyridine (3) was required, which was unknown. The
synthesis is presented in Scheme 1.
Scheme 1
O2N
O2N
O2N
DMSO
P2O5
[O]
N
N=SMe2
N
NO
N
NH2
3
2
4
NHCOMe
H2N
O2N
NHCOMe
O2N
6
N
N
N
NO2
H
5
7
Previously [13] pyridin-2-amine was converted to 2-nitrosopyridine via S,S-dimethylsulfylimine.
2 Dimethylsulfylimino-5-nitropyridine (4) can be conveniently prepared from compound 2, DMSO, and P2O5
according to [14]. However, oxidation of compound 4 with m-chloroperbenzoic acid in methylene chloride at
0°C, i.e. under conditions used for obtaining 2-nitrosopyridine in 44% yield [13], did not proceed. After the
temperature was allowed to rise to 20°C, oxidation proceeded, and a yellow crude product 3 was obtained, that,
unfortunately, was unstable in the solution and unlike 2-nitrosopyridine did not react with N-acetylphenylene-
1,4-diamine (6) in the presence of AcOH. When oxidation of compound 4 was conducted in methanol,
2,5-dinitropyridine (5) was obtained in 78% yield. This procedure for the synthesis of dinitro compound 5 seems
to have advantages over the previous [14], which needs 83% H2O2, (CF3CO)2O, and chromatographic
purification. Compound 5 reacted with aniline 6 in AcOH at room temperature and gave the product of
nucleophilic displacement of the nitro group, N-[4-(5-nitropyridin-2-ylamino)phenyl]acetamide (7) [15] in 85%
yield.
As seems likely from these experiments, the procedure [13] elaborated for the direct synthesis of
unsubstituted pyridin-2-ylazo compounds, cannot be used for the preparation of azopyridines substituted with
strong electron-withdrawing groups in the pyridine moiety: nitroso compound 3 proved to be too unstable to be
isolated and a nucleophilic center is expected on α-C rather than the nitrogen atom of the nitroso group.
Further we have investigated the possibility to obtain compound 1 from 2-amino-5-nitropyridine
1-oxide (8) by diazotization-coupling with subsequent elimination of the oxygen atom from the pyridine nitrogen
according to Scheme 2.
Although generation of diazonium salts from pyridin-2-amine 1-oxide occurs in high yields [16],
introduction of the nitro group is expected to substantially lower the stability of diazonium salt 9 promoting
substitution with N2 elimination rather than coupling reaction. The only preparation of azo dye from compound 8
has been recorded in the patent literature [17]: diazotization was performed in H3PO4 at -10°C followed by
coupling with substituted anilines in buffered aqueous medium (AcONa/AcOH); yields were not given. All our
attempts to use this method for the synthesis of compounds 11a–c were unsuccessful; the yields of azo dyes did
not exceed 1%. By examining various combinations of acid for diazotization and solvents and bases for
coupling, the best procedure was found: diazonium salt 9 generated in tetrafluoroboric acid at -15 to -20°C and
coupling with substituted anilines 10a–c performed in pyridine solution at the same temperature. Under these
conditions the yields are moderate and the azo compounds 11a–c prepared do not need chromatographic
purification. Unreacted anilines 10a–c can be washed off by diethyl ether.
30

Scheme 2
O2N
O2N
O2N
+
+
N
O
NH2
N
N
N
N2
O
N
BF4
BF4
O
8
9
R
b
c
R
N(CH2CH2OH)2
b'
O2N
N
10a–c
N
N(CH2CH2OH)2
N
a
a' c'
O
11a–c
PPh3
1a–c
a R = H, b R = OMe, c R = OC8H17
Azo compounds 11a-c were obtained as dark blue powders or crystals with golden luster; all are easily
soluble in ethanol, 11a,b also in water, but the solubility of compounds 11a-c in nonpolar solvents, for example
toluene, was less than 10–6 M. Compounds 11a–c exhibit two absorption bands (Table 1) near 250 and 600 nm;
the latter shows a strong positive solvatochromism (λmax for 11c in toluene 552 nm).
The long-wave absorption band for compound 11c, in comparison with push-pull chromophore 4-[N,N-
bis-(hydroxyethyl)amino]-4'-nitro-3-octyloxyazobenzene (12a) with the same donor unit, is blue shifted by
120 nm (in ethanol λmax of compound 12a 488 nm [9]) and is very close to 12b (λmax in ethanol 610 nm [9]).
Therefore, incorporation of the N–O function having strong push-pull properties [18] in p-nitrophenyl ortho-
position to the N=N group substantially enhances the acceptor capacity of the electron-withdrawing moiety of the
chromophore and the effect of such action is equal to introduction of two cyano groups in the acceptor moiety.
TABLE 1. Data of elemental analysis, melting points, and UV-vis spectra
of azo compounds 1a-c and 11a-c
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
λ
max , nm (lg ε ),
in ethanol
mp, °C*
C
H
N
1a
C15H17N5O4
C16H19N5O5
C23H33N5O5
C15H17N5O5
C16H19N5O6
C23H33N5O6
53.90
54.38
52.90
53.18
60.21
60.11
51.76
51.87
50.45
50.93
57.72
58.09
5.26
5.17
5.14
5.30
7.23
7.24
5.42
4.93
5.06
5.08
6.95
6.99
20.85
21.14
19.08
19.38
15.20
15.24
19.83
20.15
18.32
18.56
14.55
14.73
213-215
195-200
116-118
217-220
193-195
174-175
289 (3.86) 513 (4.48)
288 (3.99) 528 (4.47)
290 (3.88) 532 (4.43)
268 (4.22) 578 (4.80)
241 (4.23) 604 (4.79)
240 (4.30) 607 (4.78)
1b
1c
11a
11b
11c
_______
* All azo compounds that are a mixture of E/Z-isomer do not have sharp
mp, temperatures of obvious decomposition of compounds are given.
31

32

R
R
OC8H17
N(CH2CH2OH)2
O2N
N
N
12a,b
a R = H, b R = CN
Compounds 11a-c were treated with triphenylphosphine under catalysis [19] of Mo(VI)
diethyldithiocarbamate complex, MoO2[Et2NCS2]2, and novel pyridin-2-ylazo dyes 1a-c as dark red crystals
were obtained in 65-80% yield. Their chemical and nonlinear optical properties are under investigation.
The data of elemental analysis, IR, NMR, and UV spectra of all compounds obtained were consistent
with their structures (Tables 1, 2).
EXPERIMENTAL
The purity of all compounds was checked by TLC on Merck F254 silica plates. The spots were visualized
when necessary in UV light and in iodine vapor. Chromatographic separations were carried out on silica gel
(Merck, reinst) or basic alumina. Melting points were taken on a Stuart apparatus SMP 10, 1H NMR spectra were
obtained on a Varian Mercury BB 200 spectrometer (200 MHz) against TMS as an internal reference, and
elemental analysis on a VARIO EL III CHNOS Elemental Analyzer. UV-vis spectra were recorded using the
Perkin–Elmer UV-vis spectrometer Lambda 35.
2-Amino-5-nitropyridine 1-oxide (8) was obtained from 2-amino-5-nitropyridine by oxidation with m-
chloroperbenzoic acid in acetone [20], N,N-bis(2-hydroxyethyl)-2-octyloxyaniline (10c) was prepared in
accordance with [9], and MoO2(Et2NCS2)2 in the reaction of Na2MoO4 and Et2NCS2Na with HCl [21]. All other
starting materials were purchased from Acros.
2,5-Dinitropyridine (5). To a suspension of 2-dimethylsulfylimino-5-nitropyridine (1.1 g, 5.5 mmol) in
15 ml of methanol m-chloroperbenzoic acid (2.5 g, 11 mmol) in 10 ml of methanol was added slowly within 30
min with stirring. Stirring was continued for additional 30 min, and then the mixture was refrigerated overnight
at 0-5°C. The yellow precipitate was filtered off, washed with cold methanol, and dried. Yield 0.72 g (78%), mp
1
118-118.5°C (methanol). H NMR spectrum, δ, ppm (J, Hz): 8.97 (1H, d, J = 1.9, H-6); 8.91 (1H, dd, J = 1.9,
J = 9.2, H-4); 8.25 (1H, d, J = 9.2, H-3). Found, %: C 35.86; H 1.80; N 25.12. C5H3N3O4. Calculated, %: C 35.52; H
1.79; N 24.85.
N-[4-(5-Nitropyridin-2-ylamino)phenyl]acetamide (7). To compound 5 (0.1 g, 0.6 mmol) in
AcOH + ethanol (10 ml, 3:2) N-acetylphenylene-1,4-diamine (6) (0.09 g, 0.6 mmol) was added with stirring.
Stirring was continued for 2 h, and the resulting precipitate was filtered off and washed with ethanol. Yield
0.15 g (95%), mp 238-240°C (ethanol), 1H NMR spectrum, δ, ppm (J, Hz): 10.5 (1H, s, NH); 9.47 (1H, d, J = 2,
H-6 Py); 8.78 (1H, dd, J = 2, J = 8.8, H-4 Py); 8.04-7.85 (5H, m, H-3 Py, Ph); 2.12 (3H, s, COCH3). Found, %:
C 57.76; H 4.62; N 20.73. C13H12N4O3. Calculated, %: C 57.35; H 4.44; N 20.58.
5-Nitropyridin-2-diazonium 1-oxide tetrafluoroborate (9). A solution of compound 8 (2 g, 12.9 mmol)
in 16 ml HBF4 was cooled to -15 to -20°C and NaNO2 (0.88 g, 12.9 mmol) was added with stirring at such rate
that the temperature was kept below -15°C (45 min). After the addition was complete, stirring was continued for
1 h at -15 to 20 °C. The yellow suspension was used for azocoupling.
Azo compounds 11a–c were synthesized according to the general procedure illustrated by the synthesis
of 4-[N,N-bis(2-hydroxyethyl)amino]-1-(5-nitropyridin-2-yl- azo)-3-octyloxybenzene (11c). A suspension of
33

diazonium salt 9 was added dropwise within 1 h with intensive stirring to the previously cooled to -15°C
solution of compound 10c (4.0 g, 12.9 mmol) in pyridine (12 ml). Stirring was continued for 1 h, allowing the
temperature to rise to 0°C. The dark blue reaction mixture was neutralized with a saturated solution of NaHCO3,
and the oily precipitate was separated by filtration and washed with diethyl ether. Yield 1.25 g (20%).
Azo compounds 1a–c were synthesized according to the general procedure illustrated by the synthesis of
N-(2-hydroxyethyl)-2-[2-octyloxy-4-(5-nitropyridin-2-ylazo)- phenylamino]ethanol (1c). Acetone was used instead
of CHCl3 for obtaining compound 1a, the mixture CHCl3 + acetone (3:1) – for preparation of compound 1b. To
the suspension of compound 11c (1.65 g, 3.45 mmol) in 146 ml of CHCl3 triphenylphosphine (0.91 g,
3.45 mmol) and MoO2(Et2NCS2)2 (0.29 g, 0.70 mmol) were added and the mixture was stirred for 12 h. The
solvent was evaporated and the crude product recrystallized from ethyl acetate. Yield 1 g (65%).
REFERENCES
1.
2.
A. Facchetti, L. Beverina, M. E. van der Boom, P. Dutta, G. Evmenenko, A. Shukla, Ch. Stern, and
G. Pagani, T. Marks, J. Am. Chem. Soc., 128, 2142 (2006).
P. Varanasi, A. Jen, J. Chandrasekhar, I. Namboothiri, and A. Rathna, J. Am. Chem. Soc., 118, 12443
(1996).
3.
4.
5.
6.
7.
L. Cui and I. Zhao, Chem. Mater., 16, 2076 (2004).
A. Razus, L. Birzan, S. Nae, S. Razus, V. Cimpeanu, and C. Stanciu, Synth. Commun., 32, 825 (2002).
V. Ajay Mallia, P. Sudhadevi Antharjanam, and S. Das, Liq. Cryst., 30, 135 (2005).
Wenbin Lin, Weiping Lin, G. Wong, and T. Marks, J. Am. Chem. Soc., 118, 8034 (1996).
A. Razus, L. Birzan, S. Nae, L. Cristian, F. Chiraleu, and V. Cimpeanu, Dyes Pigments, 57, 223 (2003).
J. Otsuki and K. Narutaki, Bull. Chem. Soc. Jpn., 77, 1537 (2004).
8.
9.
J. Kreicberga, E. Jecs, and V. Kampars, Sci. Proc. of Riga Technical University, ser.1, 10, 46 (2005).
E. Brown and G. Granneman, J. Am. Chem. Soc., 97, 621 (1975).
10.
11.
12.
13.
14.
K. Ang, C. Donati, A. Donkor, and R. Prager, Aust. J. Chem., 45, 2034 (1992).
E. Kalatzis and C. Mastrokalos, J. Chem. Soc., Perkin Trans. 2, 1830 (1977).
E. Taylor, Ch. Tseng, and J. Rampal, J. Org. Chem., 47, 552 (1982).
O. Rakitin, O. Vlasova, L. Hmelnickii, I. Falahov, and T. Sobachina, Khim. Geterotsikl. Soedin., 1536
(1990). [Chem. Heterocycl. Comp., 26, 1281 (1990)].
15.
16.
17.
18.
19.
20.
21.
V. A. Petrov and E. L. Rewald, J. Chem. Soc., 591 (1945).
H. Becker, H. Bottcher, and H. Haife, J. Prakt. Chem., 312, 433 (1970).
J. Dehn and A. Salina, US Pat. 3249597; Chem. Abstr., 65, 9061b (1966).
C. Bourgogne, P. Masson, J.-F. Nicoud, S. Brasselet, and J. Zyss, Synth. Met., 124, 213 (2001).
X. Lu, J. Sun, and H. Tao, Synthesis, 185 (1982).
L. Deady, Synth. Commun., 7, 509 (1977).
F. Moore and M. Larson, Inorg. Chem., 6, 998 (1967)
34