Synthesis of 1-aryl-5-nitrobenzotriazoles

Article abstract of DOI:10.1007/s10593-013-1376-0

3-Aryl-1-(3-nitrophenyl)triazenes were obtained in the cyclization reaction of diazotized 3-nitroaniline with arylamines in the presence of dimethyl sulfoxide and potassium carbonate to give 1-aryl-5-nitrobenzotriazoles.

Full text of DOI:10.1007/s10593-013-1376-0

Chemistry of Heterocyclic Compounds, Vol. 49, No. 9, December, 2013 (Russian Original Vol. 49, No. 9, September, 2013)
SYNTHESIS OF 1-ARYL-5-NITROBENZOTRIAZOLES*
L. M. Gornostaev1, N. A. Bulgakova1**, and I. V. Kalashnikova1
3-Aryl-1-(3-nitrophenyl)triazenes were obtained in the cyclization reaction of diazotized 3-nitroaniline
with arylamines in the presence of dimethyl sulfoxide and potassium carbonate to give 1-aryl-
5-nitrobenzotriazoles.
Keywords: benzotriazoles, diaryltriazenes, diazotization, intramolecular heterocyclization.
Triazoles are commonly used intermediates in organic synthesis and have found application in industry,
agriculture, and medicine [1]. Many triazoles and their derivatives have high biological activity, including
antitumor activity [2, 3].
The synthesis of 1,2,3-benzotriazoles has been accomplished by various methods including
diazotization of o-diaminoarenes, reaction of aryl azides with unsaturated compounds, and heterocyclization of
o-amino-N-nitrosoarylamines or arylazobenzenes containing amino, nitro, or azido groups in the ortho position
[4]. The solid-phase synthesis of N-substituted 1H-benzotriazoles from ortho-halo- and ortho-nitroaryltriazenes
has been described by Zimmermann and Bräse [5].
In the previous work [6], we developed a synthesis for triazoles using 9,10-anthraquinone derivatives.
3-Arylanthra[1,2-d]triazole-6,11-diones were obtained by the intramolecular heterocyclization of 1-aryl-
3-anthraquinonyltriazenes entailing intramolecular nucleophilic substitution of hydrogen in the presence of a
basic catalyst.
In the present work, we have studied the feasibility of forming the triazole ring using 1,3-diaryl-
triazenes. We synthesized a series of 1,3-diaryltriazenes 1a-d containing a nitro group at position 3 in one of the
aryl residues. The synthesis of diaryltriazenes was carried out by the diazotization of 3-nitroaniline and
subsequent reaction of the resultant diazonium salt with a corresponding primary arylamine in pyridine.
The composition and structure of the obtained diaryltriazenes were confirmed by physicochemical
1
methods. The H NMR spectra of diaryltriazenes 1b,c show a doubling of the signals both for the triazene and
methyl group protons, indicating the existence of diphenyltriazenes containing an electron-withdrawing
substituent and an electron-donor substituent in two tautomeric forms. The spectra of diaryltriazenes 1a,d, which
combine a strong electron-withdrawing substituent and a weaker electron-withdrawing substituent, show
_______
*A similar paper by the authors Z. Zhou, Q.-L. Liu, W. Li, and Y.-M. Zhu was published in Heterocycles, 83,
2057 (2011). The Editors decided to publish this paper by the Russian authors in Chemistry of Heterocyclic
Compounds because it was submitted earlier.
_______
**To whom correspondence should be addressed, e-mail: gornostaev@kspu.ru.
1Krasnoyarsk State Pedagogical University named after V. P. Astaf'ev, 89 A. Lebedevoi St., Krasnoyarsk
660049, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1375-1378, September, 2013.
Original article submitted September 16, 2010; revision submitted January 12, 2012.
0009-3122/13/4909-1281©2013 Springer Science+Business Media New York
1281

broadened signal for the protons of the triazene group at 12.7-13.0 ppm. The broadening of this signal as well as
signals of the aromatic protons also suggests the existence of these compounds in two tautomeric forms.
We would like to mention that similar results for diaryltriazenes with electron-withdrawing substituents have
been described by Čimbora-Zovko et al. [7].
Obtained 3-aryl-1-(3-nitrophenyl)triazenes 1a-d undergo cyclization in the presence of potassium
carbonate in dimethyl sulfoxide over several hours to give 1-arylbenzotriazoles 2a-d in moderate yield.
2'
3'
N
NH2
1) NaNO2, H2SO4
H2O, 0–5°C
HN
N
R
6'
5'
+
2
6
5
2)
R
NH2
NO2
NO2
4
H O, Py,
0–5°C
2
1a–d
N
–
N
2'
N
3'
N
N
R
O2, K2CO3, DMSO
100–110°C
N
4
R
6'
7
5'
NO2
6
NO2
2a–d
a R = H, b R = Me, c R = OMe, d R = Cl
The structure of the obtained benzotriazoles 2a-d was confirmed by physicochemical methods. The
formation of these triazoles apparently proceeds as a result of deprotonation of diaryltriazenes 1a-d and
subsequent nucleophilic substitution of the hydrogen atom, activated by a nitro group in the para position.
The nucleophilic substitution of hydrogen in this new intramolecular cyclization proceeds with the
involvement of atmospheric oxygen. An independent experiment showed that rapid bubbling of air through the
reaction mixture reduces the reaction time, while the rate of cyclization is reduced by a factor of 15 under an
argon atmosphere.
Thus, we have found that the intramolecular cyclization of diaryltriazenes entailing intramolecular
substitution of a hydrogen atom proceeds not only for arylanthraquinolinyltriazene [6] but also for benzene
derived compounds.
EXPERIMENTAL
1
The IR spectra were recorded on a Bruker IFS-66 spectrometer in KBr pellets. The H NMR spectra
were recorded on a Bruker DRX-500 spectrometer (500 MHz) in DMSO-d6 with TMS as internal standard. The
electronic absorption spectra were recorded on an Evolution 300 spectrometer in toluene. The mass spectra were
recorded on a Finnigan MAT 8200 spectrometer with direct sample inlet and 70 eV ionizing electron energy.
The elemental analysis was carried out on a EURO EA 3000 apparatus. The melting points were determined on
a Boetius microscopic melting point apparatus. The course of the reactions and purity of the products were
monitored by thin-layer chromatography on Silufol UV-254 plates using 9:1 toluene–ethyl acetate as the eluent.
The products were recrystallized from 10:1 ethanolDMF.
3-(3-Nitrophenyl)-1-phenyltriazene (1a). A solution of 3-nitroaniline (1.00 g, 7 mmol) in concentrated
sulfuric acid (1.5 ml) and water (2 ml) was diazotized by adding NaNO2 (0.50 g, 7 mmol) in water (1 ml) over
1 h at 0-5°C [8]. Then aniline (0.64 ml, 7 mmol) in pyridine (35 ml) was added over 2 h to the resultant solution
of 3-nitrophenyldiazonium salt at the same temperature. An equal volume of water was added to the reaction
1282

mixture. The yellow precipitate formed was filtered off, washed with water and ethanol, dried in air, and
recrystallized. Yield 0.89 g (51%), mp 138°С. IR spectrum, ν, cm-1: 3289 (NH). UV spectrum, λmax, nm (log ε):
344 (4.30). 1Н NMR spectrum, δ, ppm (J, Hz): 7.17-7.27 (1Н, m, Н-4'); 7.43 (2Н, t, J = 8.0, Н-3',5' ); 7.46-7.55
(2Н, m, Н-2',6' ); 7.66 (1Н, t, J = 8.0, Н-5); 7.79-7.88 (1Н, m, Н-6); 7.88-7.99 (1Н, m, Н-4); 8.13 (1Н, s, Н-2);
12.73 (1Н, br. s, NH). Mass spectrum, m/z (Irel, %): 242 [M]+ (4), 77 [C6H5]+ (100). Found, %: С 59.10; Н 4.09;
N 23.42. C12H10N4O2. Calculated, %: С 59.50; Н 4.16; N 23.13.
Triazenes 1b-d were obtained analogously.
1-(4-Methylphenyl)-3-(3-nitrophenyl)triazene (1b). Yield 1.14g (64%), mp 103-105°С. IR spectrum,
1
ν, cm-1: 3278 (NH). UV spectrum, λmax, nm (log ε): 348 (4.26). Н NMR spectrum, δ, ppm (J, Hz) (tautomer
ratio 7:3): 2.28 (0.9Н, s, СН3); 2.35 (2.1Н, s, СН3); 7.27 (2Н, d, J = 8.0, H-3',5'); 7.48 (2Н, d, J = 8.0, Н-2',6');
7.62 (1Н, t, J = 8.0, Н-5); 7.74 (1Н, d, J = 8.0, Н-6); 7.83 (1Н, d, J = 8.0, Н-4); 8.07 (1Н, s, Н-2); 12.68 (0.7Н,
s, NH); 12.82 (0.3Н, s, NH). Mass spectrum, m/z (Irel, %): 256 [M]+ (6), 91 [C7H7]+ (100). Found, %: С 60.64;
Н 4.56; N 21.63. C13H12N4O2. Calculated, %: С 60.93; Н 4.72; N 21.86.
1-(4-Methoxyphenyl)-3-(3-nitrophenyl)triazene (1c). Yield 0.99 g (52%), mp 126-128°С. IR
1
spectrum, ν, cm-1: 3260 (NH). UV spectrum, λmax, nm (log ε): 353 (4.32). Н NMR spectrum, δ, ppm (J, Hz)
(tautomer ratio 17:3): 3.73 (0.45Н, s, ОСН3); 3.78 (2.55Н, s, ОСН3); 7.02 (2Н, d, J = 8.0, H-3',5'); 7.54 (2Н, d,
J = 8.0, Н-2',6'); 7.61 (1Н, t, J = 8.0, Н-5); 7.72 (1Н, d, J = 8.0, Н-6); 7.80 (1Н, d, J = 8.0, Н-4); 8.04 (1Н, s,
Н-2); 12.55 (0.85Н, s, NH); 12.80 (0.15Н, s, NH). Mass spectrum, m/z (Irel, %): 272 [M]+ (7), 107 [C7H7O]+
(100). Found, %: С 57.28; Н 4.26; N 20.40. C13H12N4O3. Calculated, %: С 57.35; Н 4.44; N 20.58.
1-(4-Chlorophenyl)-3-(3-nitrophenyl)triazene (1d). Yield 0.92 g (48%), mp 125°С. IR spectrum, ν,
cm-1: 3281 (NH). UV spectrum, λmax, nm (log ε): 349 (4.32). 1Н NMR spectrum , δ, ppm (J, Hz): 7.48-8.11 (8Н,
m, Н Ar); 12.93 (1Н, br. s, NH). Mass spectrum, m/z (Irel, %): 276 [M]+ (10), 111 [C6H4Cl]+ (100). Found, %:
С 52.13; Н 3.23; N 20.49. C12H9СlN4O2. Calculated, %: С 52.09; Н 3.28; N 20.25.
5-Nitro-1-phenylbenzotriazole (2a). A reaction mixture containing triazene 1a (0.85 g, 3.5 mmol),
potassium carbonate (1.40 g, 10.0 mmol), and DMSO (5 ml) was maintained at 100-110°C with vigorous
stirring for several hours until the starting substrate disappeared. Three volumes of water were added. The
brown precipitate was filtered off, washed with water and ethanol, and dried in air. Yield 0.43 g (51%), mp
128-130°С. 1H NMR spectrum, δ, ppm (J, Hz): 7.66 (1Н, t, J = 8.0, H-4'); 7.71-7.77 (2Н, m, H-3',5'); 7.89-7.93
(2Н, m, Н-2',6'); 8.12 (1Н, d, J = 9.2, Н-7); 8.45 (1Н, d. d, J = 9.2, J = 3.0, Н-6); 9.15 (1Н, d, J = 3.0, Н-4).
Mass spectrum, m/z (Irel, %): 240 [M]+ (10), 166 [M-N2-NO2]+ (36), 77 [C6H5]+ (100), 51 [C4H3]+ (69). Found,
%: С 60.30; Н 3.33; N 23.04. C12H8N4O2. Calculated, %: С 60.00; Н 3.36; N 23.32.
Benzotriazoles 2b-d were obtained analogously.
1-(4-Methylphenyl)-5-nitrobenzotriazole (2b). Yield 0.38 g (43%), mp 197-210°С. 1H NMR
spectrum, δ, ppm (J, Hz): 2.45 (3Н, s, СН3); 7.53 (2Н, d, J = 8.8, H-3',5'); 7.78 (2Н, d, J = 8.8, Н-2',6'); 8.08
(1Н, d, J = 9.2, Н-7); 8.44 (1Н, d, J = 9.2, Н-6); 9.16 (1Н, s, Н-4). Mass spectrum, m/z (Irel, %): 254 [M]+ (16), 180
[M-N2-NO2]+ (100), 152 [M-N2-NO2-H-HCN]+ (25), 91 [C7H7]+ (28), 65 [C5H5]+ (27). Found, %: С 61.74; Н 3.96;
N 22.44. С13Н10N4O2. Calculated, %: С 61.41; Н 3.96; N 22.04.
1
1-(4-Methoxyphenyl)-5-nitrobenzotriazole (2c). Yield 0.59 g (63%), mp >360°С. H NMR spectrum,
δ, ppm (J, Hz): 3.89 (3Н, s, ОСН3); 7.25 (2Н, d, J = 8.8, H-3',5'); 7.81 (2Н, d, J = 8.8, Н-2',6'); 8.02 (1Н, d,
J = 9.2, Н-7); 8.44 (1Н, d, J = 9.2, Н-6); 9.15 (1Н, s, Н-4). Mass spectrum, m/z (Irel, %): 270 [M]+ (28), 242
[M-N2]+ (15), 227 [M-N2-CH3]+ (73), 181 [M-N2-CH3-NO2]+ (100), 153 [M-N2-CH3-NO2-CO]+ (64), 92
[C6H4O]+ (26), 77 [C6H5]+ (22). Found, %: С 57.61; Н 3.69; N 20.50. C13H10N4O3. Calculated, %: С 57.78;
Н 3.73; N 20.73.
1-(4-Chlorophenyl)-5-nitrobenzotriazole (2d). Yield 0.53 g (56%), mp >360°С. 1H NMR spectrum, δ,
ppm (J, Hz): 7.81 (2Н, d, J = 8.7, Н-2',6'); 7.97 (2Н, d, J = 8.7, Н-3',5'); 8.14 (1Н, d, J = 9.1, Н-7); 8.47 (1Н, dd,
J = 9.1, J = 2.0, Н-6); 9.19 (1Н, d, J = 2.0, Н-4). Mass spectrum, m/z (Irel, %): 274 [M]+ (61), 200 [M-N2-NO2]+ (99),
165 [M-N2-NO2-Cl]+ (84), 111 [C6H4Cl]+ (100). Found, %: С 52.45; Н 2.56; N 19.96. C12H7ClN4O2. Calculated,
%: С 52.47; Н 2.57; N 20.40.
1283

REFERENCES
1.
2.
M. D. Mashkovskii, Drugs [in Russian], Novaya Volna, Moscow (2008).
B. D. Palmer, J. B. Smaill, M. Boyd, D. H. Boschelli, A. M. Doherty, J. M. Hamby, S. S. Khatana,
J. B. Kramer, A. J. Kraker, R. L. Panek, G. H. Lu, T. K. Dahring, R. T. Winters, H. D. H. Showalter, and
W. A. Denny, J. Med. Chem., 41, 5457 (1998).
3.
4.
N. Mishra, P. Arora, B. Kumar, L. C. Mishra, A. Bhattacharya, S. K. Awasthi, and V. K. Bhasin, Eur.
J. Med. Chem., 43, 1530 (2008).
H. Wamhoff, in: A. R. Katritzky and C. W. Rees (editors), Comprehensive Heterocyclic Chemistry, Vol.
5, Pergamon Press, Oxford (1984), p. 722.
5.
6.
7.
V. Zimmermann and S. Bräse, J. Comb. Chem., 9, 11 (2007).
L. M. Gornostaev and N. A. Bulgakova, Zh. Org. Khim., 37, 1416 (2001).
T. Čimbora-Zovko, A. Brozovic, I. Piantanida, G. Fritz, A. Virag, B. Alić, V. Majce, M. Kočevar,
M. Polanc, and M. Osmak, Eur. J. Med. Chem., 46, 2971 (2011).
8.
Weygand-Hilgetag, Experimental Methods in Organic Chemistry [Russian translation], Khimiya,
Moscow (1968), p. 320.
1284