Synthesis and chemical transformations of 6-amino-7-chloro-2-(2- hydroxyphenyl)-2H-benzo-triazole-4-carboxylic acid derivatives

Article abstract of DOI:10.1007/s10593-013-1165-9

6-Amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid and its analogs containing chlorine and nitro groups in the phenyl fragment have been synthesized. The special features of reduction and acetylation reactions with the obtained compounds have been studied. Methods have been developed for further chemical conversions which enable a large number of 2-(2-hydroxyphenyl)- 2H-benzotriazole-4-carboxylic acid derivatives to be obtained, with the aim of studying the dependence of their luminescence and complex-forming properties on various functional substituents.

Full text of DOI:10.1007/s10593-013-1165-9

Chemistry of Heterocyclic Compounds, Vol. 48, No. 10, January, 2013 (Russian Original Vol. 48, No. 10, October, 2012)
SYNTHESIS AND CHEMICAL TRANSFORMATIONS OF
6-AMINO-7-CHLORO-2-(2-HYDROXYPHENYL)-2H-BENZO-
TRIAZOLE-4-CARBOXYLIC ACID DERIVATIVES
V. S. Vasin1*, T. Yu. Koldaeva1, and V. P. Perevalov1
6-Amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid and its analogs containing
chlorine and nitro groups in the phenyl fragment have been synthesized. The special features of
reduction and acetylation reactions with the obtained compounds have been studied. Methods have
been developed for further chemical conversions which enable a large number of 2-(2-hydroxyphenyl)-
2H-benzotriazole-4-carboxylic acid derivatives to be obtained, with the aim of studying the dependence
of their luminescence and complex-forming properties on various functional substituents.
Keywords: 6-amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid, N- and
O-acetylation, oxidative cyclization, reductive dechlorination.
2-Phenyl-2H-benzotriazole derivatives are of high practical interest. In particular, alkyl-substituted
2-(2-hydroxyphenyl)-2H-benzotriazoles are effective UV absorbents and light stabilizers of polymeric materials
and cosmetic compositions [1]. This special feature is caused in part by the existence of an intramolecular
hydrogen bond between the o-hydroxyl of the phenyl nucleus and the azole fragment, the strength of which
affects the absorption and emission wavelength to a significant degree, and is changed upon introduction of
various substituents [2]. In addition, substituted 2-(2-hydroxyphenyl)-2H-benzotriazole derivatives possess
ligand properties [3]. In similar compounds of the naphtho[1,2-d]triazole series the carboxyl group at the
position 4 of the heteroaromatic fragment increases the stability of the coordinated compounds by forming an
additional bond with the metal, which leads to a significant change in their electron absorption spectra [4].
HO
N
N
N
R
COOH
_______
*To whom correspondence should be addressed, e-mail: vasin2258@yandex.ru.
1D. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq., Moscow 125047, Russia.
________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1620-1628, October, 2012.
Original article submitted October 14, 2011.
1508
0009-3122/13/4810-1508©2013 Springer Science+Business Media New York

In connection with the above it seemed expedient to develop a method of synthesis for new derivatives
of 6-amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid. These compounds may be
obtained by azocoupling of substituted m-phenylenediamine and o-benzoquinonediazide with subsequent
oxidative cyclization of the corresponding azo compounds [5]. We have therefore selected the available 3,5-di-
amino-4-chlorobenzoic acid (1) as the azo component containing the required carboxyl group.
Diazotization of derivatives 2a-e was carried out by the action of NaNO2/HCl, and the diazo compounds
obtained were coupled directly with 3,5-diamino-4-chlorobenzoic acid (1) in the presence of sodium acetate
(Table 1). The synthesized azo compounds 3a-e were oxidized with copper-ammonia reagent (solution of
CuSO4 in aqueous NH3) to 2H-benzotriazole-4-carboxylic acids 4a-e. To purify from copper compounds, the
reaction mixture was treated with a solution of Na2S and NaOH, and after the removal of solids the target
compounds 4a-e were isolated by acidification and purified by recrystallization.
1
R
Cl
R1
O
NH2
Cl
R1
R
O
NH2
H2N
H2N
O
CuSO4·5H2O
N
N
1) NaNO2, HCl
2) NaOAc,
N
N
NH4OH
NH2
Cl
NH2
N
R
R
COOH
2a–e
HOOC
COOH
4a–e
3a–e
1
a R = R1 = H; b R = 5-NO2, R1 = H; c R = 4-NO2, R1 = H; d R = 5-Cl, R1 = H; e R = H, R1 = Me
Further modification included studying the reduction reaction of the synthesized compounds 4a-d.
Reduction of nitro compound 4b was effected by the action of an excess of Na2S2O4 in refluxing alkaline
1
solution. Data of H NMR spectra and LCMS (liquid chromatography-mass spectrometry) of the isolated
product showed that along with nitro group reduction in these compounds a dechlorination also occurred,
leading to the formation of a mixture of 6-amino-2-(5-amino-2-hydroxyphenyl)-7-chloro-2H-benzotriazole-
4-carboxylic acid (4f) and 6-amino-2-(5-amino-2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid (5b)
(Tables 1, 2). Derivative 5b could not be obtained in pure form in spite of attempts to change the reaction
conditions (duration, amount of reducing agent). Carrying out the reaction at room temperature eliminated
dechlorination, and the sole reduction product was compound 4f.
Cl
HO
H2N
N
Na2S2O4
N
NaOH
room temp.
N
R
COOH
4f,g
HO
4a–d
H2N
N
Na2S2O4
N
NaOH, 
N
R
COOH
5a–c
4 f R = 5-NH2, g R = 4-NH2; 5 a R = H, b R = 5-NH2, c R = 5-Cl
1509

TABLE 1. Physicochemical Characteristics of the Obtained Compounds
Found, %
——————
Yield,
%
Com-
pound
Empirical
formula
Calculated, %
Mp, °С
С
H
N
C13H11ClN4O3
C13H10ClN5O5
51.07
50.91
44.64
44.40
3.59
3.62
18.36
18.27
215–217
85
93
3a
3b
(decomp., EtOH)
2.91
2.87
19.79
19.91
218–220
(decomp., EtOH)
C13H10ClN5O5
C13H10Cl2N4O3
C14H13ClN4O3
C13H9ClN4O3
C13H8ClN5O5
C13H8ClN5O5
C13H8Cl2N4O3
C14H11ClN4O3
C13H10ClN5O3
C13H10ClN5O3
C13H10N4O3
44.31
44.40
45.70
45.77
52.25
52.43
51.19
51.25
44.72
44.65
44.47
44.65
45.95
46.04
52.71
52.76
48.78
48.84
48.91
48.84
57.72
57.78
51.36
51.25
51.74
51.96
46.12
45.99
45.74
45.99
47.41
47.27
2.83
2.87
2.98
2.95
4.13
4.09
3.00
2.98
2.30
2.31
2.33
2.31
2.34
2.38
3.46
3.48
3.13
3.15
3.14
3.15
3.71
3.73
3.01
2.98
3.17
3.20
2.54
2.57
2.62
2.57
2.67
2.64
20.13
19.91
16.45
16.42
17.35
17.47
18.51
18.39
19.91
20.03
19.95
20.03
16.60
16.52
17.63
17.58
21.72
21.91
21.93
21.91
20.82
20.73
18.34
18.39
16.20
16.16
17.84
17.88
17.98
17.88
14.62
14.70
250–253
3c
3d
3e
4a
4b
4c
4d
4e
4f
94
87
87
51
62
52
65
65
37
58
52
55
48
81
54
21
15
44
(decomp., EtOH)
234–236
(decomp., EtOH)
234–236 (EtOH)
298–300
(decomp., dioxane)
>310
(dioxane)
> 310 (THF)
283–285
(decomp., EtOH)
260–262
(EtOH)
247–249
(decomp., dioxane)
262–264
(decomp., dioxane)
260–262
(decomp., EtOH)
4g
5a
5c
6a
6b
6c
6d
6e
6f
C13H9ClN4O3
C15H11ClN4O4
C15H10ClN5O6
C15H10ClN5O6
C15H10Cl2N4O4
C17H13ClN4O5
C17H12ClN5O7
C17H12Cl2N4O5
286–289
(decomp., EtOH)
>310
(AcOH)
>310
(AcOH)
>310
(AcOH)
>310
(AcOH)
232–234
(AcOH)
269–271
(AcOH)
52.61
52.52
47.11
47.07
3.40
3.37
2.77
2.79
2.89
2.86
14.35
14.41
16.22
16.15
6g
48.42
48.25
13.15
13.24
276–278
(AcOH)
50
C15H12ClN5O4
C16H13ClN4O4
C14H11ClN4O3
C14H10ClN5O5
C14H10ClN5O5
C14H10Cl2N4O3
C14H12ClN5O3
C14H12N4O3
49.86
49.80
53.39
53.27
52.81
52.76
46.35
46.23
46.15
46.23
47.84
47.61
50.35
50.39
59.10
59.15
3.31
3.34
3.65
3.63
3.45
3.48
2.82
2.77
2.74
2.77
2.88
2.85
3.61
3.62
4.23
4.25
19.41
19.36
15.43
15.53
17.73
17.58
19.34
19.25
19.34
19.25
15.78
15.86
20.91
20.98
19.66
19.71
277–278
(AcOH)
302–304
(AcOH)
233–235
(EtOH)
6h
6i
52
60
49
70
73
39
46
53
7a
7b
7c
7d
7e
8
163–165
(decomp., EtOH)
292–294
(EtOAc)
244–245
(EtOH)
257–260
(EtOAc)
236–238
(EtOAc)
1510

Amine 4g was synthesized under analogous conditions at room temperature from nitro compound 4c.
Reduction of the derivative 4c by refluxing the reaction mixture in the presence of Na2S2O4 led to the formation
of an inseparable mixture of amine 4g and the dechlorination product, as in the case of derivative 4b. Purposeful
reductive dechlorination was carried out successfully in the case of 2H-benzotriazoles 4a,d. The compounds
obtained 5a,c were isolated and characterized spectrally, and it was established by this that replacement of
chlorine by a hydrogen atom in the dichloro-substituted compound 4d occurred only in the benzotriazole ring.
Acetylation of compounds 4a-d, containing free amino and hydroxyl groups, was carried out with acetic
anhydride in refluxing acetic acid. With the aid of electronic, IR, and 1H NMR spectra it was found that both N-
and O-acetylation was possible for compounds of this series. The former proceeds fairly readily, but the
preparation of the diacetylated product required the presence of at least a 19-fold excess of acetic anhydride.
After allowing for these considerations, compounds 6a-g were synthesized.
R1O
Cl
AcHN
N
<19 equiv. Ac2O
AcOH
Na2S2O4, NaOH
room temp.
N
N
R
COOH
Cl
6a–d,i
HO
4a–e
AcHN
N
N
Cl
N
AcO
AcHN
N
>19 equiv. Ac2O
AcOH
NH2
N
COOH
6h
N
R
(from 6b)
COOH
6e–g
6 a,e,i R = H, b R = 5-NO2, c,f R = 4-NO2, d,g R = 5-Cl; 6a–d R1 = H, i R1 = Me
Only the N-acetylation product 6b was formed from compound 4b with a 19-fold excess of acetic
anhydride, due to the significantly decreased nucleophilicity of aromatic hydroxyl group in para position
relative to a nitro group. Data of IR and 1H NMR spectra (Table 2) were in full agreement with the structures of
1
the represented compounds. In the H NMR spectra of the diacylated compounds 6e-g two singlets were
observed at high field corresponding to the acetyl group protons, while in the spectra of compounds 6a-d only
one singlet was present. In the IR spectra of the diacetylated derivatives a band was observed at 1780 cm-1 for
the ester group C=O bond stretching vibrations. Acetylation of hydroxyl group in the compound 6a (transition
to compound 6e) was accompanied by a hypsochromic shift of the electronic absorption spectrum long wave
maximum by 25 nm, which resulted from the disappearance of the intramolecular hydrogen bond.
Nitro compound 6b, containing an acetylamino group in the position 6, was reduced without heating by
the procedure for synthesizing compound 4f, giving 6-acetylamino-7-chloro-2-(5-amino-2-hydroxyphenyl)-
2H-benzotriazole-4-carboxylic acid (6h). In the course of this reaction the chlorine atom and acetyl function in
the molecule were retained.
Cl
HO
HO
H2N
H2N
N
N
H2SO4, MeOH
4a–d,f, 5a
;
N
N
Dioxane, , 8 h
N
N
R
COOMe
COOMe
8
7a–e
(from 5а)
7 a R = H, b R = 5-NO2, c R = 4-NO2, d R = 5-Cl, e R = 5-NH2
1511

TABLE 2. Spectral Characteristics of the Synthesized Compounds
UV spectrum,
Com-
pound
IR spectrum,
1Н NMR spectrum, δ, ppm (J, Hz)
λabs, nm
ν, cm-1
(ε, l mol-1 cm-1)
·
·
1
2
3
4
460 (19370)
467 (23290)
3425, 3350 (NH2), 6.67 (1Н, s, Н-5); 6.91-6.96 (2H, m, H-3',5');
1700 (C=O)
3a
7.20 (1H, dt, 3J = 7.3, 4J = 1.5, H-4');
7.58 (1H, dd, 3J = 7.3, 4J = 1.5, H-6');
8.05 (2H, br. s, 5-NH2); 11.00 (1H, br. s, OH)
3475, 3465, 3400
6.61-6.65 (3Н, m, H-5, 3-NH2);
3b
(NH2), 1705 C=O), 7.12 (1H, d, J = 8.8, Н-3');
1505,
8.06 (1H, dd, 3J = 8.8, 4J = 2.2, Н-4');
1320 (NO2)
8.22 (2H, br. s, 5-NH2); 8.42 (1H, d, J = 2.2, Н-6');
12.00 (2H, br. s, OH, COOH)
505 (31080)
470 (23890)
3465, 3455,
3390 (NH2),
6.66 (1Н, s, Н-5); 6.75 (2Н, s, 3-NH2);
3c
7.67 (1H, dd, 3J = 8.2, 4J = 1.5, Н-5');
1710 (C=O), 1530, 7.74-7.77 (2H, m, H-3',6'); 8.41 (2H, br. s, 5-NH2);
1350 (NO2) 11.80 (1H, br. s, OH)
3475, 3400 (NH2), 6.55-6.57 (3Н, m, H-5, 3-NH2);
3d
1705 (C=O)
6.97 (1H, d, J = 8.8, Н-3');
7.20 (1H, dd, 3J = 8.8, 4J = 2.0, Н-4');
7.57 (1H, d, J = 2.0, Н-6'); 7.90 (1H, s, Н-5);
8.13 (2H, br. s, 5-NH2); 11.75 (1H, br. s, OH)
470 (23680)
3390, 3320 (NH2), 3.92 (3Н, s, OСH3); 6.45 (2H, s, 3-NH2);
3e
1695 (C=O)
6.54 (1Н, s, H-5);
7.01 (1H, dt, 3J = 7.3, 4J = 1.5, H-5');
7.19 (1H, dd, 3J = 7.3, 4J = 1.5, H-3');
7.34 (1H, dt, 3J = 7.3, 4J = 1.5, H-4');
7.45 (1H, dd, 3J = 7.3, 4J = 1.5, H-6');
8.20 (2H, br. s, 5-NH2)
390 (12640)
400 (13170)
3465, 3390 (NH2), 6.03 (2Н, s, NH2);
4a
4b
1700 (С=О)
7.05 (1H, dt, 3J = 7.4, 4J = 1.5, H-5');
7.16 (1H, dd, 3J = 7.4, 4J = 1.5, H-3');
7.39 (1H, dt, 3J = 7.4, 4J = 1.5, H-4');
7.82 (1Н, s, Н-5);
7.95 (1H, dd, 3J = 7.4, 4J = 1.5, H-6')
3475, 3400 (NH2), 6.13 (2Н, s, NH2); 7.33 (1H, d, J = 7.3, Н-3');
1695 (C=O), 1560, 7.92 (1H, s, Н-5);
1350 (NO2)
8.26 (1H, dd, 3J = 7.3, 4J = 1.5, Н-4');
8.74 (1H, d, J = 1.5, Н-6');
12.20 (1H, br. s, COOH)
420 (13820)
398 (11230)
3455, 3380 (NH2), 6.23 (2Н, s, NH2); 7.89-7.95 (3H, m, H-5,3',5');
1705 (C=O), 1530, 8.17 (1H, d, J = 8.6, Н-6'); 11.55 (1H, br. s, OH);
4c
1350 (NO2)
13.20 (1H, br. s, COOH)
3460, 3390 (NH2), 6.21 (2Н, s, NH2); 7.18 (1H, d, J = 8.8, Н-3');
4d
1700 (С=О)
7.48 (1H, dd, 3J = 8.8, 4J = 2.2, Н-4');
7.87 (1H, d, J = 2.2, Н-6'); 7.90 (1H, s, Н-5);
10.92 (1H, br. s, OH)
365 (7570)
3420, 3355 (NH2), 3.80 (3Н, s, OСH3); 5.92 (2H, s, NH2)
1690 (C=O)
4e
7.14 (1H, dt, 3J = 7.3, 4J = 1.5, H-5');
7.31 (1H, dd, 3J = 7.3, 4J = 1.5, H-3');
7.56-7.60 (2H, m, H-4',6'); 7.78 (1Н, s, H-5);
12.50 (1Н, br. s, COОН)
410 (11850)
405 (13110)
385 (9750)
3415, 3340 (NH2), 6.15 (2Н, s, 6-NH2);
1700 (С=О)
4f
6.79 (1H, dd, 3J = 7.3, 4J = 1.5, Н-4');
6.94 (1H, d, J = 7.3, Н-3'); 7.44 (1H, d, J = 1.5, Н-6');
7.89 (1H, s, Н-5); 10.28 (1H, s, OH)
3440, 3430, 3365
5.60 (2H, br. s, 4'-NH2); 5.98 (2Н, s, 6-NH2);
4g
5a
(NH2), 1705 (С=О) 6.25-6.28 (2H, m, Н-3',5');
7.64 (1H, d, J = 8.1, Н-6'); 7.81 (1H, s, Н-5);
10.70 (1H, br. s, OH)
3475, 3400 (NH2), 5.85 (2H, br. s, NH2); 6.94 (1H, d, J = 1.5, H-7);
1700 (C=O)
7.00 (1H, dt, 3J = 7.3, 4J = 1.5, H-5');
7.20 (1H, dd, 3J = 7.3, 4J = 1.5, H-3');
7.34 (1H, dt, 3J = 7.3, 4J = 1.5, H-4');
7.71 (1H, d, J = 1.5, H-5); 7.93 (1H, dd,
3J = 7.3, 4J = 1.5, H-6'); 12.00 (1H, br. s, COOH)
1512

TABLE 2 (continued)
1
2
3
4
385 (9610)
3475, 3400 (NH2), 6.21 (2Н, s, NH2); 6.94 (1H, d, J = 1.5, H-7);
5c
1705 (C=O)
7.22 (1H, d, J = 7.3, Н-3');
7.33 (1H, dd, 3J = 7.3, 4J = 1.5, Н-4');
7.68 (1H, d, J = 1.5, Н-5);
7.91 (1H, d, J = 1.5, Н-6')
350 (15600)
3295 (N-H), 1690
(С=О)
2.18 (3Н, s, СH3);
6a
7.07 (1H, dt, 3J = 7.3, 4J = 1.5, H-5');
7.18 (1H, dd, 3J = 7.3, 4J = 1.5, H-3');
7.47 (1H, dt, 3J = 7.3, 4J = 1.5, H-4');
7.79 (1H, dd, 3J = 7.3, 4J = 1.5, H-6');
8.44 (1Н, s, H-5); 10.01 (1Н, s, NН);
10.59 (1Н, s, ОН)
345 (15470)
370 (19250)
3390 (N-H), 1710, 2.19 (3H, s, CH3); 7.36 (1H, d, J = 8.1, Н-3');
6b
1695 (C=O), 1560, 8.33 (1H, dd, 3J = 8.1, 4J = 2.2, Н-4');
1350 (NO2)
8.48 (1H, s, Н-5); 8.64 (1H, d, J = 2.2, Н-6');
9.99 (1H, s, NH); 12.15 (1H, br. s, COOH)
3350 (N-H), 1715, 2.20 (3H, s, CH3);
6с
1700 (C=O), 1530, 7.90 (1H, dd, 3J = 8.8, 4J = 2.2, Н-5');
1350 (NO2)
7.97 (1H, d, 4J = 2.2, Н-3');
8.13 (1H, d, 3J = 8.8, Н-6'); 8.50 (1H, s, H-5);
9.85 (1H, s, NH); 11.45 (2H, br. s, OH, COOH)
360 (16220)
320 (18620)
3370 (N-H), 1715, 2.18 (3H, s, CH3); 7.20 (1H, d, J = 8.8, Н-3');
1700 (C=O)
6d
6e
7.53 (1H, dd, 3J = 8.8, 4J = 2.2, Н-4');
7.85 (1H, d, J = 2.2, Н-6'); 8.44 (1H, s, Н-5);
10.01 (1H, s, NH); 10.79 (1H, br. s, OH);
13.10 (1H, br. s, COOH)
3310 (N-H), 1775, 2.18 (3H, s, NCOCH3); 2.30 (3H, s, OCOCH3);
1695 (C=O)
7.47-7.68 (3Н, m, H-3',4',5');
8.20 (1H, dd, 3J = 7.3, 4J = 1.5, H-6');
8.45 (1H, s, H-5); 10.08 (1H, s, NH);
13.30 (1H, br. s, COOH)
335 (21150)
320 (14360)
3360 (N-H), 1775, 2.19 (3H, s, NCOCH3); 2.39 (3H, s, OCOCH3);
1715, 1695 (C=O), 8.42-8.56 (4H, m, H-5,3',5',6'); 10.08 (1H, s, NH);
6f
1530, 1350 (NO2)
12.70 (1H, br. s, COOH)
3380 (N-H), 1780, 2.18 (3H, s, NCOCH3); 2.31 (3H, s, OCOCH3);
1710, 1695 (C=O) 7.53 (1H, d, J = 8.8, Н-3');
7.74 (1H, dd, 3J = 8.8, 4J = 2.2, Н-4');
6g
8.24 (1H, d, J = 2.2, Н-6'); 8.46 (1H, s, Н-5);
10.01 (1H, s, NH); 11.60 (1H, br. s, COOH)
398 (6160)
310 (14200)
400 (13600)
3415, 3340 (NH2), 2.18 (3H, s, CH3);
6h
6i
3325 (N-H), 1710, 6.83 (1H, dd, 3J = 8.1, 4J = 2.2, Н-4');
1700 (C=O)
6.96 (1H, d, J = 8.1, Н-3');
7.32 (1H, d, J = 2.2, Н-6'); 8.43 (1H, s, Н-5);
10.00 (1H, s, 6-NH); 10.04 (1H, s, OH)
3290 (N-H), 1690,
1670 (C=O)
2.17 (3Н, s, COСH3); 3.81 (3Н, s, 2'-OСH3);
7.19 (1H, dt, 3J = 7.3, 4J = 1.5, H-5');
7.37 (1H, dd, 3J = 7.3, 4J = 1.5, H-3');
7.64-7.68 (2H, m, H-4',6'); 8.40 (1Н, s, H-5);
10.01 (1Н, s, NН); 12.85 (1Н, br. s, COОН)
3475, 3400 (NH2), 3.93 (3H, s, CH3); 6.15 (2H, br. s, NH2);
7a
1710 (C=O)
7.05 (1H, dt, 3J = 7.3, 4J = 1.5, H-4');
7.16 (1H, dd, 3J = 7.3, 4J = 1.5, H-3');
.42 (1H, dt, 3J = 7.3, 4J = 1.5, H-5');
7.80 (1Н, s, Н-5);
7.93 (1H, dd, 3J = 7.3, 4J = 1.5, H-6');
10.68 (1H, s, OH)
403 (7930)
3475, 3400 (NH2), 3.95 (3H, s, CH3); 7.33 (1H, d, J = 7.3, Н-3');
1720 (C=O), 1560, 7.94 (1H, s, Н-5);
1350 (NO2)
7b
7c
8.28 (1H, dd, 3J = 7.3, 4J = 1.5, Н-4');
8.67 (1H, d, J = 1.5, Н-6')
420 (14830)
3460, 3390 (NH2), 3.93 (3H, s, CH3); 6.27 (2H, s, NH2);
1715 (C=O), 1530, 7.87-7.95 (3H, m, Н-5,3',5');
1350 (NO2)
8.11 (1H, d, J = 8.0, Н-6'); 11.47 (1H, s, OH)
1513

TABLE 2 (continued)
1
2
3
4
405 (14260)
3450, 3375 (NH2), 3.93 (3H, s, CH3); 6.20 (2H, s, NH2);
7d
1710 (C=O)
7.17 (1H, d, J = 7.3, Н-3');
7.47 (1H, dd, 3J = 7.3, 4J = 1.5, Н-4');
7.86 (1H, s, Н-5); 7.93 (1H, d, J = 1.5, Н-6');
10.84 (1H, s, OH)
412 (12120)
400 (12600)
3425, 3350 (NH2), 3.94 (3H, s, CH3); 5.05 (2H, br. s, 5'-NH2);
7e
8
1715 (С=О)
6.21 (2H, s, 6-NH2);
6.68 (1H, dd, 3J = 7.3, 4J = 1.5, Н-4');
6.88 (1H, d, J = 7.3, Н-3'); 7.29 (1H, s, Н-5);
7.93 (1H, d, J = 1.5, Н-6'); 10.01 (1H, s, OH)
3475, 3400 (NH2), 3.94 (3H, s, CH3); 5.85 (2H, br. s, NH2);
1710 (C=O)
7.04-7.08 (2H, m, H-7,5');
7.15 (1H, dd, 3J = 7.3, 4J = 2.2, H-3');
7.38 (1H, dt, 3J = 7.3, 4J = 2.2, H-4');
7.78 (1H, d, J = 2.2, H-5);
8.00 (1H, dd, 3J = 7.3, 4J = 1.5, H-6');
11.03 (1H, s, OH)
For further assessment of the hydroxyl and carboxyl group effects on the selectivity of complex
formation, and on spectral differences of the initial ligand and complexes, 2H-benzotriazole derivatives
containing a 2-methoxy group in the phenyl ring (compounds 4e and 6i) and a 4-methoxycarbonyl group in the
benzotriazole fragment (compounds 7a-e and 8) were also synthesized.
A series of new substituted 6-amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid
derivatives has therefore been synthesized, aided by procedures developed for selective reduction, acetylation,
and reductive dechlorination.
EXPERIMENTAL
The IR spectra were recorded on a Specord M80 spectrometer in nujol. Electronic absorption spectra
1
were recorded on a Specord M400 spectrophotometer in ethanol. H NMR spectra were recorded on a Bruker
AM-300 instrument (300 MHz) in DMSO-d6, internal standard was TMS. Liquid chromatography-mass spectra
(LCMS) were recorded on a Surveyor MSQ spectrometer, column was Phenomenex Onyx Monolithic C18
254.6 mm, eluent 0.1% HCOOH–MeCN, flow rate 1.5 ml/min, method of ionization APCI. Elemental analysis
was carried out on a vario Micro cube instrument. Melting points were determined on a PTP-M instrument. A
check on the progress of reactions and the purity of the obtained compounds was effected by TLC on Sorbfil
plates (silica gel CTX-1A, UV-254).
3,5-Diamino-4-chlorobenzoic Acid (1). A solution of NaOH (13.20 g, 0.33 mol) in H2O (90 ml) was
added dropwise to a boiling solution of 3,5-diamino-4-chlorobenzoic acid isobutyl ester (29.12 g, 0.12 mol) in
ethanol (100 ml). The obtained mixture was left for 1 h, then cooled, and acidified with conc. HCl to pH 7. The
precipitated solid was filtered off, washed with water and dried at 50oC. Yield 20.38 g (91%). Pink solid
substance; mp > 300oC. IR spectrum, ν, cm-1: 3375, 3300 (NH2), 1695 (C=O). 1H NMR spectrum, δ, ppm: 6.67
(2H, s, H-2,6); 4.42 (4H, br. s, 2NH2). Found, %: C 45.14; H 3.75; N 15.07. C7H7ClN2O2. Calculated, %:
C 45.06; H 3.78; N 15.01.
3,5-Diamino-4-chloro-2-(2-hydroxyphenyl)diazenylbenzoic Acid (3a). A solution of o-aminophenol
(2a) (4.47 g, 29 mmol) in H2O (83.0 ml) and conc. HCl (7.3 ml) was diazotized with a solution of NaNO2
(2.07 g, 30 mmol) in H2O (5.0 ml) for 1 h 15 min at a temperature no higher than 10oC. The completion of the
reaction was determined with the aid of starch-iodide paper. The solution of diazonium salt obtained was added
over 15 min to a solution of 3,5-diamino-4-chlorobenzoic acid (1) (5.41 g, 29 mmol) in EtOH (200 ml) and H2O
1514

(155 ml), after which a concentrated solution of NaOAc was added to pH 6. The reaction mixture was stirred for
3.5 h. The precipitated solid was filtered off, washed with water, and dried at 50oC. A solid substance of red
color was obtained.
3,5-Diamino-4-chloro-2-(2-hydroxy-5-nitrophenylazo)benzoic Acid (3b), 3,5-diamino-4-chloro-
2-(2-hydroxy-4-nitrophenylazo)benzoic acid (3c), 3,5-diamino-4-chloro-2-(5-chloro-2-hydroxyphenyl-
azo)benzoic acid (3d), and 3,5-diamino-4-chloro-2-(2-methoxyphenylazo)benzoic acid (3e) were obtained
analogously. All azo compounds were red, solid substances.
6-Amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic Acid (4a). A solution of
copper-ammonium reagent, obtained from CuSO4·5H2O (20.97 g, 84 mmol), 25% aqueous NH3 (75 ml), and
H2O (35 ml), was added dropwise to a refluxing solution of azo compound 3a (7.36 g, 24 mmol) in a mixture of
2-PrOH (50 ml) and 25% aqueous NH3 (150 ml). The reaction mixture was stirred for 10 h, then cooled, and
acidified to pH 6 with 10% HCl. The precipitated solid was filtered off, suspended in a solution of NaOH (2.52 g,
63 mmol) and Na2S·9H2O (8.64 g, 36 mmol) in H2O (900 ml) and stirred for 1 h at 90oC. The mixture was
filtered, the filtrate cooled, and acidified with 10% HCl to pH 5.5. The precipitated solid was filtered off,
washed with water, and dried at 50oC. After recrystallization from dioxane the product was obtained as a
yellow, solid substance.
6-Amino-7-chloro-2-(2-hydroxy-5-nitrophenyl)-2H-benzotriazole-4-carboxylic acid (4b) (reaction time
20 h), 6-amino-7-chloro-2-(2-hydroxy-4-nitrophenyl)-2H-benzotriazole-4-carboxylic acid (4c) (reaction time
30 h, NaOH solution was used for purification from copper ions), 6-amino-7-chloro-2-(5-chloro-2-hydroxy-
phenyl)-2H-benzotriazole-4-carboxylic acid (4d) (reaction time 3 h), 6-amino-7-chloro-2-(2-methoxy-
phenyl)-2H-benzotriazole-4-carboxylic acid (4e) (reaction time 5 h) were obtained analogously. The
derivatives were solid substances of yellow (compounds 4b,e), orange (4c), or beige color (4d).
6-Amino-2-(5-amino-2-hydroxyphenyl)-7-chloro-2H-benzotriazole-4-carboxylic Acid (4f).
A
solution of Na2S2O4 (7.83 g, 45 mmol) in H2O (30 ml) was added dropwise to a solution of compound 4b (1.05 g,
3 mmol) and NaOH (3.00 g, 75 mmol) in H2O (50 ml). The reaction mixture was stirred at room temperature for
4.5 h, then acidified with 10% HCl to pH 6. The precipitated solid was filtered off, washed with water, and
dried at 50oC. After extraction with acetone in a Soxhlet apparatus, the organic layer was evaporated, and a
yellow, solid substance was obtained.
6-Amino-2-(4-amino-2-hydroxyphenyl)-7-chloro-2H-benzotriazole-4-carboxylic acid (4g) (from
compound 4c) and acid 6h (from compound 6b) were obtained analogously at room temperature. On refluxing
the reaction mixture for 4.5 h 6-amino-2-(2-hydroxyphenyl-2H-benzotriazole-4-carboxylic acid (5a) (from
compound 4a) and 6-amino-2-(5-chloro-2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid (5c) (from
compound 4d) were obtained. All the compounds were yellow, solid substances.
On refluxing the reaction mixture, compound 4b gave a mixture of compound 4f and 6-amino-2-(5-ami-
no-2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid (5b). Mp 250-290oC (decomp.). 1H NMR
spectrum, δ, ppm (J, Hz) (ratio 4f : 5b was 1:2): 5.74 (1.33H, br. s, NH2 (5b)); 6.05 (0.66H, s, NH2 (4f));
6.77-6.84 (1H, m, H-4' (4f + 5b)); 6.92-6.97 (1.66H, m, H-3' (4f + 5b), H-7 (5b)); 7.43-7.46 (1H m, H-6' (4f +
5b)); 7.72 (0.66H, d, J = 1.6, H-5 (5b)); 7.89 (0.33H, s, H-5 (4f)); 10.32 (0.33H, s, OH (4f)); 10.60 (0.66H, s,
OH (5b)). Chromatography with mass spectral detector gave m/z (τ, min): 286 [M+H]+ (1.40) (5b), 320 [M+H]+
(1.51) (4f).
6-Acetylamino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic Acid (6a). Ac2O
(1.9 ml, 20 mmol, 4 equiv.) was added dropwise to a suspension of the benzotriazole 4a (1.52 g, 5 mmol) in
glacial AcOH (100 ml). The reaction mixture was refluxed for 7.5 h, diluted with cold water (100 ml), and
stirred for a further 20 min. The precipitated solid was filtered off, and dried under reduced pressure. After
recrystallization from glacial acetic acid, a yellowish, solid substance was obtained.
6-Acetylamino-7-chloro-2-(2-hydroxy-4-nitrophenyl)-2H-benzotriazole-4-carboxylic acid (6c) and
6-acetylamino-7-chloro-2-(5-chloro-2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid (6d) were
obtained analogously from compounds 4c,d using 8 equiv. Ac2O. On using 19 equiv. Ac2O, 6-acetylamino-
1515

7-chloro-2-(2-hydroxy-5-nitrophenyl)-2H-benzotriazole-4-carboxylic acid (6b) and 6-acetylamino-
7-chloro-2-(2-methoxyphenyl)-2H-benzotriazole-4-carboxylic acid (6i) were obtained from compounds 4b,e.
On using 19 equiv. Ac2O, the diacetylated product 2-(2-acetoxyphenyl)-6-acetylamino-7-chloro-2H-
benzotriazole-4-carboxylic acid (6e) was obtained from compound 4a. On using 50 equiv. Ac2O, 2-(2-acet-
oxy-4-nitrophenyl)-6-acetylamino-7-chloro-2H-benzotriazole-4-carboxylic acid (6f) and 2-(2-acetoxy-
5-chlorophenyl)-6-acetylamino-7-chloro-2H-benzotriazole-4-carboxylic acid (6g) were obtained from
compounds 4c,d. 6-Acetylamino-2-(5-amino-2-hydroxyphenyl)-7-chloro-2H-benzotriazole-4-carboxylic
acid (6h) was obtained by treating nitro derivative 6b with NaOH and Na2S2O4 at room temperature by the
procedure for obtaining compound 4f. All the acetyl derivatives were beige (compounds 6a,d-i) or yellowish
(compounds 6b,c) solid substances.
6-Amino-7-chloro-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic Acid Methyl Ester (7a).
96% H2SO4 (1 ml) was added dropwise to a suspension of acid 4a (0.91 g, 3 mmol) in dioxane (30 ml) and
methanol (25 ml). The reaction mixture was refluxed for 8 h, then cooled. The precipitated solid was filtered off
and dried at reduced pressure. After recrystallization from EtOH, a greenish-yellow solid substance was
obtained.
6-Amino-7-chloro-2-(2-hydroxy-5-nitrophenyl)-2H-benzotriazole-4-carboxylic acid methyl ester
(7b), 6-amino-7-chloro-2-(2-hydroxy-4-nitrophenyl)-2H-benzotriazole-4-carboxylic acid methyl ester (7c),
6-amino-7-chloro-2-(5-chloro-2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic acid methyl ester (7d),
and 6-amino-2-(2-hydroxyphenyl)-2H-benzotriazole-4-carboxylic Acid (8) were obtained analogously. All
esters were yellow, solid substances.
The synthesis of 6-amino-2-(5-amino-2-hydroxyphenyl)-7-chloro-2H-benzotriazole-4-carboxylic
acid methyl ester (7e) was carried out in an analogous manner, after which 25% aqueous NH3 was added
dropwise to the obtained suspension to pH 7. The solid was filtered off and dried in vacuum. An orange, solid
substance was obtained.
REFERENCES
1.
2.
G. Woessner, G. Goeller, J. Rieker, H. Hoier, J. J. Stezowski, E. Daltrozzo, M. Neurieter, and
H. E. A. Kramer, J. Phys. Chem. B, 89, 3629 (1985).
B. M. Krasovitskii and B. M. Bolotin, Organic Luminophores [in Russian], Khimiya, Moscow (1984),
p. 100.
3.
4.
5.
T. Carofiglio, E. Solari, C. Floriani, A. Chiesi-Villa, and C. Rizzoli, Polyhedron, 15, 4435 (1996).
E. Steiner and G. Schetty, Helv. Chim. Acta, 52, 380 (1969).
M. P. Schmidt and A. Hagenbocker, Ber. Dtsch. Chem. Ges., A/B, 54, 2191 (1921).
1516