Reactivity of diazoazoles and azolediazonium salts in C-azo coupling reactions

Article abstract of DOI:10.1007/s11172-005-0259-7

The comparative reactivity of heterocyclic diazo compounds and the corresponding diazonium salts in C-azo coupling reactions was studied using imidazole, pyrazole, and triazole derivatives as examples.The reactivities of pyrazole- and imidazole-derived di

Full text of DOI:10.1007/s11172-005-0259-7

354
Russian Chemical Bulletin, International Edition, Vol. 54, No. 2, pp. 354—365, February, 2005
Reactivity of diazoazoles and azolediazonium salts
in Cꢀazo coupling reactions
E. V. Sadchikovaꢀ and V. S. Mokrushin
Ural State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 5483. Eꢀmail: selena@htf.ustu.ru
The comparative reactivity of heterocyclic diazo compounds and the corresponding diazoꢀ
nium salts in Cꢀazo coupling reactions was studied using imidazole, pyrazole, and triazole
derivatives as examples. The reactivities of pyrazoleꢀ and imidazoleꢀderived diazonium salts
are much lower than those of thiadiazoleꢀ and 1,2,4ꢀtriazoleꢀderived diazonium salts but
higher than those of pyrrole and indole diazo compounds.
Key words: heterocyclic diazo compounds, diazonium salts, diazoimidazoles, diazoꢀ
pyrazoles, imidazolediazonium salts, pyrazolediazonium salts, 1,2,4ꢀtriazolediazonium salts,
Cꢀazo coupling, reactivity.
The Cꢀazo coupling reaction characterizes the reacꢀ
xylene, toluene, and benzene were used as the ranking
reagents.
Study of the reactions of diazo compounds 1a—c with
tivity of aromatic diazonium salts. By varying the activity
of the azo components, one can estimate qualitatively the
reactivity of the diazonium derivative. Pycryldiazonium
sulfate, which forms azo compounds with anisole and
mesitylene, is known1 to be among the most reactive aroꢀ
matic compound in these reactions. The reactivity of hetꢀ
erocyclic diazonium salts varies over a very broad range.
Thus the pyrrolediazonium salt does not react even with
βꢀnaphthol,2 while the diazonium salts derived from
isothiazole, benzothiazole, 1,2,4ꢀtriazole, and tetrazole
give azo compounds with phenethole and mesitylene.3
The highest reactivity is found for imidazoleꢀ2ꢀdiazoꢀ
nium salts obtained in 85% phosphoric acid, which unꢀ
dergo coupling with benzene,4,5 apparently, through proꢀ
tonation of the imidazole ring. Heterocyclic diazo comꢀ
pounds with structures similar to quinonediazides and
aliphatic diazo compounds react only with the most acꢀ
tive azo components,6—9 although often it is not defined
what particular form, either diazo compound or the diꢀ
azonium salt, takes part in the reaction. It is noteworthy
that these forms can exist in the prototropic equilibrium.10
The purpose of the present study was to compare the
reactivities of heterocyclic diazo compounds, viz., 4ꢀniꢀ
troꢀ5ꢀdiazoimidazole (1a), ethyl 5ꢀdiazoimidazoleꢀ (1b),
and 5ꢀdiazopyrazoleꢀ4ꢀcarboxylates (1c), and the correꢀ
sponding diazonium salts 2a—c, as well as 4,5ꢀdicyanoꢀ
imidazoleꢀ2ꢀdiazonium chloride (2d) and 1,2,4ꢀtriazoleꢀ
3ꢀdiazonium sulfate (2e) under conditions that rule out
prototropic interconversions. βꢀNaphthol, N,Nꢀdimethylꢀ
aniline, resorcinol, 1,3,5ꢀtrimethoxybenzene, 1,3ꢀdiꢀ
methoxybenzene, mꢀ and pꢀcresol, anisole, mesitylene,
aromatic azo components has shown that the formation
of azo coupling products depends on the nature of the
substituent and the heterocycle structure. For example,
diazoimidazole 1a (δH(2) 7.72, ν(NN) = 2220 cm–1) conꢀ
taining a strong electronꢀwithdrawing group, forms azo
compounds with βꢀnaphthol, N,Nꢀdimethylaniline, reꢀ
sorcinol, 1,3,5ꢀtrimethoxybenzene, and 1,3ꢀdimethoxyꢀ
benzene (3a—7a) (Scheme 1), whereas with anisole or
pꢀcresol, no reaction was observed. As the reactivity of
the azo component used in the reaction decreases, the
time required for the formation of azo compounds subꢀ
stantially increases, while their yields decrease. The startꢀ
ing diazo compound is not completely converted into the
final product, irrespective of the reaction time.
Scheme 1
R = 2ꢀhydroxyꢀ1ꢀnaphthyl (3a), 4ꢀMe2NC6H4 (4a),
2,4ꢀ(OH)2C6H3 (5a), 2,4,6ꢀ(MeO)3C6H2 (6a), 2,4ꢀ(MeO)2C6H3 (7a)
Ethyl 5ꢀdiazopyrazoleꢀ4ꢀcarboxylate (1c) (δH(3) 8.34,
ν(NN) = 2210 cm–1) is also coupled with βꢀnaphthol,
N,Nꢀdimethylaniline, resorcinol, 1,3,5ꢀtrimethoxybenꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 348—358, February, 2005.
1066ꢀ5285/05/5402ꢀ0354 © 2005 Springer Science+Business Media, Inc.

Reactivity of diazoazoles and azolediazonium salts
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
355
Scheme 2
X = CH, Y = N (1b, 3b—5b, 9b,e); X = N, Y = CH (1c, 3c—5c, 9c,f); R = 2ꢀhydroxynaphthyl (3b,c), 4ꢀMe2NC6H4 (4b,c)
zene, and 1,3ꢀdimethoxybenzene at room temperature to
give azo compounds 3c—7c, respectively (Scheme 2).
Under similar conditions, ethyl 5ꢀdiazoimidazoleꢀ4ꢀcarbꢀ
oxylate (1b) (δH(2) 7.69, ν(NN) = 2190 cm–1) reacts only
with βꢀnaphthol, N,Nꢀdimethylaniline, and resorcinol,
both mono (5b) and bis (8) azo coupling products being
formed in the latter case. The structures of compounds
5b,c and 8 were proved by physicochemical methods and
by transforming them into the corresponding benzo(diꢀ
azolo)triazines 9a—c. Bisꢀazo coupling can be prevented
by using a tenfold excess of the azo component.
9b,e, it was found that azo coupling is accompanied by
demethylation of one methoxy group to give compounds
10a,b (see Scheme 2).
A study of the reactivity of 4,5ꢀdicyanoimidazoleꢀ2ꢀ
(2d; ν(NN) = 2299 cm–1), 4ꢀnitroꢀ (2a; δH(2) 8.43,
ν(NN) = 2270 cm–1) and 4ꢀethoxycarbonylimidazoleꢀ
5ꢀdiazonium (2b; δH(2) 8.26, ν(NN) = 2265 cm–1),
4ꢀethoxycarbonylpyrazoleꢀ5ꢀdiazonium (2c), and
1,2,4ꢀtriazoleꢀ3ꢀdiazonium (2e) salts with respect to azo
coupling showed that the position of the diazonium group
in the ring, unlike the nature of the heterocycle, does not
affect much their reactivities. In the case of 2a—d, couꢀ
pling with βꢀnaphthol, N,Nꢀdimethylaniline, resorcinol,
1,3,5ꢀtrimethoxybenzene, and 1,3ꢀdimethoxybenzene
occurs rather smoothly at room temperature to give the
Diazoimidazole 1b is coupled with polymethoxy deꢀ
rivatives of benzene in an aprotic solvent only on heating.
Using spectroscopic techniques and chemical transforꢀ
mations into the corresponding benzo(imidazo)triazines

356
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Sadchikova and Mokrushin
corresponding azo compounds 3a—dꢀ7a—d, whereas the
reaction of salts 2a,b,d with mꢀ and pꢀcresol proceeds
only on refluxing in glacial acetic acid for 3—5 h and
gives azo compounds 11a,b,d and 12a,b,d, respectively
(Scheme 3). Compounds 11c and 12c could not be preꢀ
pared. None of the diazonium cations studied reacts with
anisole or mesitylene under similar conditions.
to obtain 1,2,4ꢀtriazole azo derivatives 6e and 7e, which
have not been described previously.
Scheme 4
Scheme 3
i. 25% H2SO4. ii. 50% H2SO4.
R1 = R2 = R3 = OMe (6e); R1 = H, R2 = R3 = OMe (7e);
R
R
R
1 = R3 = H, R2 = OMe (13a); R1 = R2 = R3 = Me (14a);
1 = H, R2 = OH (15a); R1 = R2 = OMe (15b);
1 = H, R2 = OMe (15c)
2a—7a, 11a, 12a: X = CH, Y = N, R = NO2;
2b—7b, 11b, 12b: X = CH, Y = N, R = COOEt;
2c—7c: X = N, Y = CH, R = COOEt;
As an attempt to enhance the reactivity of diazonium
salts by increasing the acidity of the medium,8 we studied
diazotization of 5ꢀaminoꢀ4ꢀnitroimidazole (16) in conꢀ
centrated phosphoric acid and the subsequent coupling of
the resulting diazonium salt with inert azo components
such as anisole, mesitylene, pꢀxylene, and benzene. The
reactions with anisole and mesitylene were found to give
azo compounds 13b and 14b, whereas pꢀxylene and benꢀ
zene did not react (Scheme 5).
R´ = 2ꢀhydroxyꢀ1ꢀnaphthyl (3a—d), 4ꢀMe2NC6H4 (4a—d),
2,4ꢀ(OH)2C6H3 (5a—d), 2,4,6ꢀ(MeO)3C6H2 (6a—d),
2,4ꢀ(MeO)2C6H3 (7a—d), 2ꢀMeꢀ4ꢀOHC6H3 (11a,b,d),
2ꢀMeꢀ5ꢀOHC6H3 (12a,b,d)
Whereas pyrazoleꢀ and imidazolediazonium salts exꢀ
hibit comparable reactivities with respect to azo coupling,
the 1,2,4ꢀtriazoleꢀ3ꢀdiazonium derivative 2e (δH(2) 9.00,
ν(NN) = 2275 cm–1) is more reactive and reacts with
anisole and mesitylene giving rise to azo compounds 13a
and 14a (Scheme 4). In addition, upon the reaction of
salt 2e with hydroxy and polymethoxy benzene derivaꢀ
tives in 25% sulfuric acid, only benzo[2,1ꢀe][1,2,4]triꢀ
azolo[5,1ꢀc]ꢀasꢀtriazines 15a—c, resulting from intramoꢀ
lecular cyclization of the intermediate azo compounds
5e—7e, were isolated as the final products. We were able
to find conditions that allow one to avoid cyclization and
The results obtained suggest that the reactivities of
imidazolediazonium salts increase, possibly, due to proꢀ
tonation of the second N atom of the heterocycle. Neverꢀ
theless, the reactivity is still markedly lower than those of
benzoimidazolediazonium salts able to form coupling
products with inert azo components such as xylenes, toluꢀ
ene, and benzene, although it becomes comparable with
the reactivity of 1,2,4ꢀtriazoleꢀ3ꢀdiazonium (2e).
Study of the reactions of 4,5ꢀdicyanoimidazoleꢀ2ꢀdiꢀ
azonium chloride (2d) with benzene and pꢀxylene at
Scheme 5
R = 4ꢀMeOC6H4 (13b), 2,4,6ꢀMe3C6H2 (14b)

Reactivity of diazoazoles and azolediazonium salts
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
357
60—70 °C has shown that in this case, no azo compounds
are formed; instead, the reaction gives arylimidazoles
17a—c (Scheme 6). The reaction with toluene gives a
mixture of metaꢀ and paraꢀisomers in 1 : 1 ratio; however,
only paraꢀsubstituted product 17b was isolated in a pure
state.
the formation of compounds 18a,b from diazoimidazole
1a is preceded most likely by the formation of a carbeneꢀ
type species. Thus, the form of the reacting diazo comꢀ
pound has a substantial influence on both the coupling
reaction rate and the course of reactions with nitrogen
evolution, although does not change the reaction routes.
In order to find out what class of organic substances
the nitrogenꢀcontaining fiveꢀmembered heterocycles conꢀ
taining a CNN fragment as a substituent resemble most
closely and also to predict their behavior in typical chemiꢀ
cal transformations, we analyzed a broad array of their
properties, as well as calculated and spectroscopic charꢀ
acteristics. The stretching frequency of the diazo group
increases in the following sequence: 3ꢀdiazopyrrole < 2ꢀdiꢀ
azopyrrole < 3ꢀ and 4ꢀdiazopyrazoles < 4ꢀdiazoimidꢀ
azole < 4ꢀdiazoꢀ1,2,3ꢀtriazole < 2ꢀdiazoimidazole < 3ꢀdiꢀ
azoꢀ1,2,4ꢀtriazole < 5ꢀdiazotetrazole. On passing from
diazoazoles to the corresponding diazonium salts,
the stretching band for the functional group shifts by
70—140 cm–1. A similar sequence of absorption frequenꢀ
cies of heterocyclic diazonium salt is as follows: pyrroleꢀ
3ꢀdiazonium salts < pyrazoleꢀ4ꢀdiazonium salts < imidꢀ
azoleꢀ4ꢀdiazonium salts ≤ pyrazoleꢀ3ꢀdiazonium salts ≤
≤ 1,2,3ꢀtriazoleꢀ4ꢀdiazonium salts = imidazoleꢀ2ꢀdiazoꢀ
nium salts = 1,2,4ꢀtriazoleꢀ3ꢀdiazonium salts. It is noteꢀ
worthy that the ν(N2+) stretching frequency observed for
the azolediazonium salts is similar to that of the diazoꢀ
nium group in aromatic diazonium salts. As regards their
physicochemical characteristics, diazoazoles 1 we studied
resemble more closely aromatic diazonium salts than aliꢀ
phatic diazo compounds; therefore, they should tend to
undergo transformations involving the terminal N atom
of the diazo group. However, as compared with the
azolediazonium and aromatic cations, diazo compounds 1
are expected to be almost inert in the reactions typical of
aromatic diazonium compounds, whereas the activity of
imidazolediazonium salts 2 in these transformations is
comparable with that of aromatic salts, which is conꢀ
firmed by our studies.
Scheme 6
R = H (a), Me (c)
It is noteworthy that the involvement of less reactive
4ꢀnitroꢀ5ꢀdiazoimidazole (1a) in similar transformations
with benzene and toluene resulted in 5ꢀarylꢀ4ꢀnitroꢀsubꢀ
stituted imidazoles 18a,b in 38 and 23% yields, respecꢀ
tively, only after longꢀterm refluxing (Scheme 7). The
structure of the synthesized arylimidazoles was confirmed
by physicochemical methods (Table 1).
Scheme 7
In addition, we detected a certain relationship beꢀ
tween the chemical shift of the proton located in the azole
ring and diazoazole reactivity (Fig. 1). It can be seen from
Fig. 1 that the lowerꢀfield the position of the proton sigꢀ
nal, the higher the activity of the diazonium derivative in
Cꢀazo coupling reactions. This type of proton behavior
reflects the decrease in the electron density in the heteroꢀ
cyclic system, which finally increases the electrophilicꢀ
ity of the diazonium group and the reactivity of the
diazo compound. Indeed, diazoimidazoles 1a,b (δH 7.69
and 7.71) react only with the most reactive azo compoꢀ
nents, whereas triazoleꢀ3ꢀdiazonium salts 2e (δH 9.0) and
4ꢀnitroimidazoleꢀ5ꢀdiazonium salts 2a (δH 8.43) react with
a more extensive series of aromatic derivatives, and the
ring protonation allows one to prepare azo compounds
with simple arenes.
R = H (a), Me (b)
The different durations of the chemical transformaꢀ
tions and different product yields can be attributed to
different mechanisms leading to 2ꢀ and 5ꢀarylꢀsubstituted
imidazoles. For example, the synthesis of compounds
17a—c from salt 2d follows an ionic mechanism, whereas

358
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Sadchikova and Mokrushin
Table 1. Melting points, reaction times, yields and data of elemental analysis of the products
Comꢀ
pound
M.p.
/°C
Reaction
time
(method)*
Yield
(%)
Found
Calculated
Molecular
formula
(%)
N
C
H
3a
3b
3c
3d
4a
4b
4с
4d
5a
5b
5c
5d
6a
6b
6c
6d
6e
7a
7b
7c
7d
7e
9a
9b
9c
9d
>300
5 days (A)
2 h (B)
14 days (A)
0.5 h (B)
4 days (A)
17 h (B)
10 days (A)
3 h (B)
65 h (A)
10 min (B)
75 h (A)
15 min (B)
75 h (A)
10 min (B)
5 min
70
82
53
85
71
90
92
98
60
36
53
44
59
62
96
55.12
55.13
61.77
61.93
62.11
61.93
62.38
62.50
50.52
50.77
58.66
58.52
58.43
58.52
58.79
58.86
43.22
43.38
51.98
52.17
52.10
52.17
52.06
51.97
46.87
46.91
53.98
53.89
53.77
53.89
53.76
53.85
50.04
50.19
47.78
47.66
55.22
55.26
55.32
55.26
55.24
55.32
51.32
51.50
51.18
50.95
55.94
55.81
55.74
55.81
57.40
57.35
3.14
3.20
4.51
4.55
4.34
4.55
2.91
2.80
4.54
4.65
6.07
5.96
5.97
5.96
4.13
4.18
2.75
2.83
4.47
4.38
4.26
4.38
2.35
2.38
4.22
4.26
5.40
5.43
5.52
5.43
3.88
3.87
5.11
4.98
3.94
4.00
5.36
5.30
5.33
5.30
3.64
3.57
4.88
4.75
3.92
3.80
4.00
3.90
3.92
3.90
4.47
4.44
24.92
24.73
17.86
18.05
17.82
18.05
29.33
29.15
32.38
32.29
24.19
24.37
24.48
24.37
37.06
36.96
27.79
28.10
19.89
20.28
20.36
20.28
33.14
33.06
22.93
22.79
16.87
16.76
16.98
16.76
26.97
26.91
26.37
26.60
25.34
25.26
18.34
18.41
18.48
18.41
29.86
29.77
29.78
30.03
26.27
26.40
21.83
21.70
22.06
21.70
20.41
20.58
C13H9N5O3
C16H14N4O3
C16H14N4O3
C15H8N6O
228—229
210—212
261—263
>300
C11H12N6O2
C14H17N5O2
C14H17N5O2
C13H11N7
209—210
187—188
275—277
238—240
220—221
182—183
283—285
>300
14 days
74
C9H7N5O4
25 days (A)
3 h (B)
1 h (C)
12 days (D)
10 h
38
62
45
67
85
C12H12N4O4
C12H12N4O4
C11H6N6O2
C12H13N5O5
C15H18N4O5
C15H18N4O5
C14H12N6O3
C11H13N5O3
C11H11N5O4
C14H16N4O4
C14H16N4O4
C13H10N6O2
C10H11N5O2
C18H16N8O5
C12H10N4O3
C12H10N4O3
C13H12N4O3
15 days (A)
4 h (B)
10 h (B)
68
82
62
210—211
230—231
213—215
156—158
>300
3 h (B)
0.5 h (B)
0.5 h
71
83
76
30 days (A)
6 h (B)
3 days (B)
32
41
54
117—119
220—222
239—241
200—203
<300
4 h (B)
65
8 days (A)
1 h (B)
1 h
51
71
98
3.5 h
32
<300
3.5 h (A)
5 h (B)
2 h
59
66
72
264—266
205—207
2 h
77
(to be continued)

Reactivity of diazoazoles and azolediazonium salts
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
359
Table 1 (continued)
Comꢀ
pound
M.p.
/°C
Reaction
time*
(method)
Yield
(%)
Found
Calculated
Molecular
formula
(%)
N
C
H
9e
243—245
230—231
153—155
163—167
198—200
235—238
278—281
>300
3 h (A)
4 h (B)
3 h
68
57
80
55.75
55.63
55.79
55.63
53.86
53.79
52.41
52.50
48.67
48.59
56.94
56.93
57.01
57.14
48.64
48.59
56.67
56.93
56.89
57.14
53.05
53.20
48.32
48.59
61.19
61.38
55.23
55.59
51.16
51.34
52.11
51.95
53.58
53.73
68.18
68.04
69.34
69.22
70.11
70.26
57.31
57.14
59.34
59.11
4.61
4.67
4.63
4.67
4.94
4.86
4.94
5.04
3.62
3.67
5.17
5.14
3.12
3.20
3.71
3.67
5.04
5.14
3.28
3.20
4.58
4.46
3.78
3.67
6.27
6.09
5.19
5.05
2.84
2.69
4.06
3.92
3.68
3.51
3.18
3.11
3.56
3.87
4.39
4.54
3.65
3.73
4.30
4.46
18.72
18.53
18.39
18.53
19.52
19.30
17.12
17.49
28.38
28.33
20.38
20.43
33.43
33.32
28.51
28.33
20.13
20.43
33.15
33.32
34.19
34.46
28.14
28.33
32.19
32.53
26.88
27.01
37.18
37.42
30.05
30.29
34.64
34.81
28.74
28.85
26.68
26.91
25.13
25.21
22.07
22.21
20.43
20.68
C14H14N4O4
C14H14N4O4
C13H14N4O4
C14H16N4O5
C10H9N5O3
C13H14N4O3
C12H8N6O
C10H9N5O3
C13H14N4O3
C12H8N6O
C9H9N5O
9f
10a
10b
11a
11b
11d
12a
12b
12d
13a
13b
14a
14b
15a
15b
15c
17a
17b
17c
18a
18b
3 days
3 h
87
57
4 month (A)
3.5 h (B)
4 month (A)
3 h (B)
23
74
29
82
46
1 h
5 h (B)
33
208—210
200—201
170—172
264—266
165—166
205—208
181—183
179—180
174—178
243—244
140—142
132—134
256—259
287—289
4 month (A)
4.5 (B)
4 h
11
56
34
20 h
37
12 h (A)
20 h (B)
8 days
72
45
28
C10H9N5O3
C11H13N5
50 h (A)
84 h (B)
0.5 h
41
36
68
C12H13N5O2
C8H5N5O
0.25 h
98
96
83
58
42
38
23
C10H9N5O2
C9H7N5O
1 h
48 days
48 days
48 days
3 month
3 month
C11H6N4
C12H8N4
C13H10N4
C9H7N3O2
C10H9N3O2
* The preparation method (A, B, C, D) is given according to Experimental.
Thus, the experimental data we obtained on the reacꢀ
tivity of various diazoimidazole species are in good agreeꢀ
ment with the regularities elucidated by analysis of specꢀ
troscopic characteristics. Studies of azo coupling of
diazoazoles and the corresponding diazonium salts with a
broad range of azo components have shown that the reacꢀ
tivities of the imidazoleꢀ and pyrazolediazonium salts are
comparable with the reactivity of benzenediazonium chloꢀ
ride, while the 4ꢀnitroimidazoleꢀ5ꢀdiazonium sulfate and
phosphate are comparable with the most reactive diazoꢀ
nium salt, viz., picryldiazonium sulfate, which has a preꢀ
dictive value for determining the scope of application of

360
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Sadchikova and Mokrushin
B. βꢀNaphthol (0.52 g, 3.6 mmol) was added with stirring at
~20 °C to a solution of 3 mmol of diazonium salt 2a—c in 5 mL
of glacial acetic AcOH. The reaction mixture was kept at ~20 °C
(2a,c) or 70 °C (2b) until the starting diazonium salt disapꢀ
peared (see Table 1). The precipitate was filtered off and washed
with ether.
2ꢀ(2ꢀHydroxyꢀ1ꢀnaphthyl)azoimidazoleꢀ4,5ꢀdicarbonitrile
(3d). βꢀNaphthol (0.49 g, 3.32 mmol (method A)) or (0.6 g,
4.17 mmol (method B)) was added with stirring at ~20 °C to a
solution of diazo compound 1d (0.5 g, 3.47 mmol) or diazonium
salt 2d (0.5 g, 2.77 mmol), respectively, in 10 mL of anhydrous
MeCN. The reaction mixture was kept for 3 h (A) or for
10 days (B) until the starting compound disappeared, and the
precipitate was filtered off.
4ꢀRꢀ5ꢀ[4ꢀ(N,NꢀDimethylamino)phenyl]azoazoles 4a—c (genꢀ
eral procedure). A. N,NꢀDimethylaniline (0.46 mL, 3.6 mmol)
was added with stirring at ~20 °C to a solution of diazo
compound 1a—c (3 mmol) in 10 mL of anhydrous MeCN or
CHCl3. The reaction mixture was kept until the starting
diazoimidazole disappeared (see Table 1). The solvent was evapoꢀ
rated in vacuo to dryness, and the residue was recrystallized from
50% EtOH.
4ꢀNitroꢀ5ꢀ[4ꢀ(N,Nꢀdimethylamino)phenyl]azoimidazole (4a).
B. N,NꢀDimethylaniline (0.32 mL, 2.53 mmol) was added with
stirring at ~20 °C to a solution of diazonium salt 2a (0.5 g,
2.11 mmol) in 15% H2SO4. The reaction mixture was kept for
10 min. The precipitate was filtered off and an additional amount
of the product was extracted from the filtrate with chloroform.
The extract was concentrated in vacuo to dryness. The precipiꢀ
tate was recrystallized from 50% EtOH.
Fig. 1. Reactivity of diazoazoles in Cꢀazo coupling with different
azo components vs. chemical shift of the azole ring proton in the
1H NMR spectra.
azole diazonium salts in other reactions. It was found that
the imidazole derivatives occupy an intermediate position
in the series of heterocyclic diazonium salts; their reacꢀ
tivities are much lower than those of the thiadiazoleꢀ11
and 1,2,4ꢀtriazoleꢀderived7 diazonium salts, which react
with inactive azo components, but are somewhat higher
than those of pyrroleꢀ and indoleꢀderived2 diazonium deꢀ
rivatives.
Experimental
Ethyl 5ꢀ[4ꢀ(N,Nꢀdimethylamino)phenyl]azoimidazoleꢀ4ꢀcarbꢀ
oxylate (4b) and 5ꢀ[4ꢀ(N,Nꢀdimethylamino)phenyl]azopyrazoleꢀ
4ꢀcarboxylate (4c). B. N,NꢀDimethylaniline (0.46 mL,
3.61 mmol) was added with stirring at ~20 °C to diazonium salt
2b (0.5 g, 3.01 mmol) in 10 mL of glacial AcOH. The reaction
mixture was kept for 15 min. The solvent was evaporated, and
the residue was recrystallized from 50% EtOH.
2ꢀ[4ꢀ(N,NꢀDimethylamino)phenyl]ꢀ (4d) and 2ꢀ(2,4ꢀdiꢀ
hydroxyphenyl)azoimidazoleꢀ4,5ꢀdicarbonitrile (5d). N,NꢀDiꢀ
methylaniline (0.42 mL, 3.32 mmol) or resorcinol (0.37 g,
3.32 mmol) was added with stirring at ~20 °C to a solution of
diazonium salt 2d (0.5 g, 2.77 mmol) in 10 mL of dry MeCN or
CHCl3. The reaction mixture was kept for 5 min or for 10 h,
respectively, until the starting compound disappeared. The preꢀ
cipitate that formed was filtered off.
4ꢀNitroꢀ5ꢀ(2,4ꢀdihydroxyphenyl)azoimidazole (5a). Resorciꢀ
nol (3.47 g, 4.3 mmol) was added with stirring at ~20 °C to a
solution of diazo compound 1a (0.5 g, 3.6 mmol) in 15 mL of
CHCl3 or MeCN. The reaction mixture we kept for 14 days. The
precipitate was filtered off and recrystallized from EtOH.
Ethyl 5ꢀ(2,4ꢀdihydroxyphenyl)azoimidazoleꢀ (5b) and
5ꢀ(2,4ꢀdihydroxyphenyl)azopyrazoleꢀ4ꢀcarboxylates (5c). A. Reꢀ
sorcinol (3.31 g, 30.1 mmol) was added in portions with stirring
at 10 °C over a period of 2 h to a solution of diazo compound 1b
(0.5 g, 3.01 mmol) in 25 mL of MeCN. The temperature was
gradually brought to 20 °C and the reaction mixture was kept
under these conditions for 25 days. The solvent was evaporated
in vacuo and the residue was triturated with ether and filtered.
The precipitate was recrystallized from acetone.
Spectroscopic studies were performed using analytically and
chromatographically pure samples. IR spectra of the syntheꢀ
sized compounds were recorded on a Specord IRꢀ75 instrument
(in KBr pellets and CaF2 cells). UV spectra were measured on a
Beckmanꢀ26 spectrophotometer. 1H NMR spectra were reꢀ
corded on a Bruker WRꢀ250 instrument (250 MHz) in a
DMSOꢀd6—CCl4 mixture (δ scale, internal Me4Si). The reacꢀ
tions were monitored and the purity of the products was checked
by TLC on Silufol UVꢀ254 and Sorbfil UVꢀ254 plates (silica gel
STCꢀ1A as the sorbent) using the following solvent systems:
BuOH—AcOH—H2O, 4 : 1 : 1 (I); CHCl3—EtOH, 3 : 1 (II);
and CHCl3—EtOH, 10 : 1 (III).
The results of elemental analysis of the obtained compounds
(C, H, N) correspond to calculated data. Their spectroscopic
characteristics are listed in Table 2. The melting points were not
corrected.
The starting diazoazoles and diazonium salts were prepared
from the corresponding heterocyclic amines.10 4ꢀAminoꢀ5ꢀ
nitroimidazole and ethyl 5ꢀaminoimidazoleꢀ4ꢀcarboxylate were
synthesized by known procedures.12,13 2ꢀAminoꢀ4,5ꢀdicyanoꢀ
imidazole, ethyl 5ꢀaminopyrazoleꢀ4ꢀcarboxylate and 3ꢀaminoꢀ
1,2,4ꢀtriazole are commercially available.
4ꢀRꢀ5ꢀ(2ꢀHydroxyꢀ1ꢀnaphthyl)azoimidazoles 3a,b and ethyl
5ꢀ(2ꢀhydroxyꢀ1ꢀnaphthyl)azopyrazoleꢀ4ꢀcarboxylate (3c) (genꢀ
eral procedure). A. βꢀNaphthol (0.52 g, 3.6 mmol) was added
with stirring at ~20 °C to a solution of diazo compound 1a—c
(3 mmol) in CHCl3 or MeCN. The reaction mixture was kept
until the starting diazoimidazole was completely converted (see
Table 1). The solvent was evaporated in vacuo and the residue
was washed with water and EtOH.
B. Resorcinol (0.4 g, 3.61 mmol) was added with stirring at
~20 °C to a solution of diazo compound 1b (0.5 g, 3.01 mmol) in

Reactivity of diazoazoles and azolediazonium salts
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
361
Table 2. Spectroscopic characteristics of the products
Comꢀ
pound
IR, ν/cm–1
1H NMR, δ (J/Hz)
NH
C=O
C=N,
CN
N=N (NO2)
3a
3b
3320
—
1630,
1610
1570
(1360)
6.72 (d, 1 H, H(4´), J = 9.7); 7.45—7.80 (m, 3 H, H(5´), H(6´), H(7´));
7.88 (s, 1 H, H(2)); 7.95 (d, 1 H, H(3´), J = 9.7); 8.66 (d, 1 H, H(8´),
J = 8.3); 13.92 (br.s, 1 H, ОH); 15.90 (s, 1 H, NH)
1.42 (t, 3 H, ОСH2СH3, J = 7.0); 4.42 (q, 2 H, ОСН2СН3, J = 7.0);
6.97 (d, 1 H, H(4´), J = 9.4); 7.47 (dd, 1 H, H(6´), J1 = 7.0, J2 = 7.6);
7.61 (dd, 1 H, H(7´), J1 = 8.6, J2 = 7.0); 7.70 (d, 1 H, H(5´), J = 7.6);
7.97 (d, 1 H, H(3´), J = 9.4); 8.02 (s, 1 H, H(2)); 8.64 (d, 1 H, H(8´),
J = 8.6); 9.71 (br.s, 1 H, ОН); 15.55 (s, 1 H, NH)
3350
1670
1610,
1590
—
3c
3d
3430, 1690
3380
1630
—
1.40 (t, 3 H, ОСН2СН3, J = 7.0); 4.36 (q, 2 H, ОСН2СН3, J = 7.0);
6.73 (d, 1 H, H(4´), J = 9.5); 7.45 (dd, 1 H, H(7´), J1 = 7.3, J2 = 7.3);
7.58 (dd, 1 H, H(6´), J1 = 7.0, J2 = 7.3); 7.70 (d, 1 H, H(5´), J = 7.0);
7.91 (d, 1 H, H(3´), J = 9.5); 8.19 (s, 1 H, H(3)); 8.52 (d, 1 H, H(8´),
J = 7.3); 10.20 (br.s, 1 H, ОН); 15.86 (s, 1 H, NH)
5.95 (s, 1 H, ОН); 6.81 (d, 1 H, H(3´), J = 9.5); 7.59 (dd, 1 H, H(6´),
J1 = 7.9, J2 = 7.0); 7.59 (dd, 1 H, H(7´), J1 = 7.0, J2 = 8.2); 7.70 (d, 1 H,
H(5´), J = 7.9); 7.95 (d, 1 H, H(4´), J = 9.5); 8.66 (d, 1 H, H(8´), J = 8.2);
15.03 (br.s, 1 H, NH)
3180,
3430,
3535
—
1610,
1585
2220
4a
4b
3440
3420
—
1600
1590
1560
(1340)
—
3.00, 3.12 (both s, 3 H each, NMe); 6.88 (d, 2 H, H(3´), H(5´), J = 9.3);
7.78 (s, 1 H, H(2)); 7.82 (d, 2 H, H(2´), H(6´), J = 9.3); 15.73 (br.s, 1 H, NH)
1.35 (t, 3 H, ОСН2СН3, J = 7.0); 3.07 (s, 6 Н, NMe2); 4.32 (q, 2 H, ОСН2СН3,
J = 7.0); 6.84 (d, 2 H, H(3´), H(5´), J = 9.5); 7.78 (d, 2 H, H(2´), H(6´),
J = 9.5); 7.79 (s, 1 H, H(2)); 14.72 (s, 1 H, NH)
1685
4c
3430
1690
1580
1595
—
1.31 (t, 3 H, ОСН2СН3, J = 7.0); 3.10 (s, 6 Н, NMe2); 4.24 (q, 2 H, ОСН2СН3,
J = 7.0); 7.06 (d, 2 H, H(3´), H(5´), J = 9.4); 7.88 (d, 2 H, H(2´), H(6´),
J = 9.4); 8.13 (s, 1 H, H(3)); 13.54 (s, 1 H, NH)
3.17 (s, 6 H, NMe2); 6.83 (d, 2 H, H(3´), H(5´), J = 9.5); 7.82 (d, 2 H, H(2´),
H(6´), J = 9.5); 14.83 (br.s, 1 H, NH)
6.36 (d, 1 H, H(3´), J = 2.4); 6.58 (dd, 1 H, H(5´), J1 = 8.9, J2 = 2.4);
7.69 (d, 1 H, H(6´), J = 8.9); 7.93 (s, 1 H, H(2)); 9.24, 10.73 (both s, 1 H
each, ОН); 13.44 (br.s, 1 H, NH)
4d
5a
3460
3420
—
—
2240,
2215
1560
1610,
1600
(1345)
5b
5c
5d
3400
3425
3230
1705
1700
—
1610,
1595
—
—
1.35 (t, 3 H, ОСН2СН3, J = 7.0); 4.36 (q, 2 H, ОСН2СН3, J = 7.0);
6.35 (d, 1 H, H(3´), J = 2.4); 6.56 (dd, 1 H, H(5´), J1 = 8.9, J2 = 2.4);
7.67 (d, 1 H, H(6´), J = 8.9); 7.93 (s, 1 H, H(2)); 9.09, 10.66 (both s, 1 H
each, ОН); 13.16 (br.s, 1 H, NH)
1.35 (t, 3 H, ОСН2СН3, J = 6.7); 4.30 (q, 2 H, ОСН2СН3, J = 6.7);
6.29 (s, 1 H, H(3´)); 6.51 (d, 1 H, H(5´), J = 8.4); 7.64 (d, 1 H, H(6´),
J = 8.4); 8.03 (s, 1 H, H(3)); 9.29, 10.56 (both s, 1 H each, ОН);
13.00 (br.s, 1 H, NH)
6.35 (d, 1 H, H(3´), J = 2.4); 6.44 (dd, 1 H, H(5´), J1 = 9.2, J2 = 2.4);
7.62 (d, 1 H, H(6´), J = 9.2); 10.36, 10.88 (both s, 1 H each, ОН);
14.91 (br.s, 1 H, NH)
3.85 (s, 6 H, 2 OMe); 3.91 (s, 3 H, OMe); 6.40 (s, 2 H, H(3´), H(5´));
7.80 (s, 1 H, H(2)); 13.40 (s, 1 H, NH)
1605,
1585
1600
1590
2240,
2215
6a
6b
3480
3440
—
1560
(1340)
—
1690
1600,
1580
1.36 (t, 3 H, ОСН2СН3, J = 7.0); 3.83 (s, 6 Н, 2 OMe); 3.89 (s, 3 H, OMe);
4.35 (q, 2 H, ОСН2СН3, J = 7.0); 6.33 (s, 2 H, H(3´), H(5´)); 7.74 (s, 1 H,
H(2)); 14.79 (s, 1 H, NH)
6c
3510, 1680
3455
1590
1590
—
1.19 (t, 3 H, ОСН2СН3, J = 6.7); 3.81 (s, 6 Н, 2 ОMe); 3.88 (s, 3 H, ОMe);
4.17 (q, 2 H, ОСН2СН3, J = 6.7); 6.37 (s, 2 H, H(3´), H(5´)); 8.21 (s, 1 H,
H(3)); 13.37 (br.s, 1 H, NH)
3.89 (s, 6 H, 2 OMe); 3.93 (s, 3 H, OMe); 6.32 (s, 2 H, H(3´), H(5´));
14.97 (br.s, 1 H, NH)
6d
6e
3460,
3500
3450
—
—
2230
—
1600,
1590
3.86 (s, 6 H, 2 OMe); 3.92 (s, 3 H, OMe); 6.38 (s, 2 H, H(3´), H(5´));
8.81 (s, 1 H, H(5)); 13.39 (br.s, 1 H, NH)
(to be continued)

362
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Sadchikova and Mokrushin
Table 2 (continued)
Comꢀ
pound
IR, ν/cm–1
1H NMR, δ (J/Hz)
NH
C=O
C=N,
CN
N=N (NO2)
7a
7b
3500
—
1600
1560
(1350)
3.92, 4.01 (both s, 3 H each, OMe); 6.70 (dd, 1 H, H(5´), J1 = 8.9, J2 = 2.1);
6.81 (d, 1 H, H(3´), J = 2.1); 7.71 (d, 1 H, H(6´), J = 8.9); 7.85 (s, 1 H, H(2));
13.43 (br.s, 1 H, NH)
1.36 (t, 3 H, ОСН2СН3, J = 7.0); 3.85, 3.89 (both s, 3 H each, OMe); 4.35 (q, 2 H,
ОСН2СН3, J = 7.0); 6.87 (dd, 1 H, H(5´), J1 = 8.6, J2 = 2.4); 6.98 (d, 1 H,
H(3´), J = 2.4); 7.73 (d, 1 H, H(6´), J = 8.6); 7.91 (s, 1 H, H(2));
13.54 (br.s, 1 H, NH)
1.35 (t, 3 H, ОСН2СН3, J = 7.0); 3.90, 3.98 (both s, 3 H each, OMe); 4.36 (q, 2 H,
ОСН2СН3, J = 7.0); 6.68 (dd, 1 H, H(5´), J1 = 8.6, J2 = 2.4); 6.80 (d, 1 H,
H(3´), J = 2.4); 7.67 (d, 1 H, H(6´), J = 8.6); 8.29 (s, 1 H, H(3));
14.22 (br.s, 1 H, NH)
3440
3510
1690
1700
1600,
1580
—
—
7c
1590,
1570
7d
7e
9a
9b
9c
9d
3440
3425
3400
—
—
1580
1590
1600
1600
1610
1600
2230
—
3.94, 4.03 (both s, 3 H each, OMe); 6.57 (dd, 1 H, H(5´), J1 = 9.2, J2 = 2.4);
6.73 (d, 1 H, H(3´), J = 2.4); 7.74 (d, 1 H, H(6´), J = 9.2);
13.20 (br.s, 1 H, NH)
3.90, 3.99 (both s, 3 H each, OMe); 6.58 (dd, 2 H, H(5´), J1 = 8.8, J2 = 2.2);
6.71 (dd, 1 H, H(3´), J = 2.2); 7.68 (d, 1 H, H(6´), J = 8.8); 8.46 (s, 1 H, H(5));
13.39 (br.s, 1 H, NH)
1.41 (m, 6 Н, 2 ОСН2СН3); 4.44 (m, 4 Н, 2 ОСН2СН3); 7.36 (d, 1 H, H(7),
J = 9.2); 8.12 (s, 1 H, H(2´)); 8.51 (d, 1 H, H(6), J = 9.2); 9.56 (s, 1 H, H(1));
14.03 (br.s, 1 H, ОH); 14.54 (br.s, 1 H, NH)
1.40 (t, 3 H, ОСН2СН3, J = 7.0); 4.44 (q, 2 H, ОСН2СН3, J = 7.0);
7.29 (dd, 1 H, H(7), J1 = 8.9, J2 = 2.1); 7.69 (d, 1 H, H(9), J = 2.1);
8.42 (d, 1 H, H(6), J = 8.9); 9.18 (s, 1 H, H(1))
1.39 (t, 3 H, ОСН2СН3, J = 7.0); 4.41 (q, 2 H, ОСН2СН3, J = 7.0);
7.37 (dd, 1 H, H(7), J1 = 9.3, J2 = 2.3); 7.61 (d, 1 H, H(9), J = 2.3);
8.55 (d, 1 H, H(6), J = 9.3); 8.71 (s, 1 H, H(2)); 11.95 (br.s, 1 H, ОН)
1.39 (t, 3 H, ОСН2СН3, J = 7.0); 4.06 (s, 3 H, ОMe); 4.41 (q, 2 H, ОСН2СН3,
J = 7.0); 7.45 (dd, 1 H, H(7), J1 = 9.2, J2 = 2.1); 7.92 (d, 1 H, H(9), J = 2.1);
8.53 (d, 1 H, H(6), J = 9.2); 8.82 (s, 1 H, H(2))
—
1720
1700
1715
1695
—
—
—
—
—
—
9e
9f
—
—
1700
1685
1605
1610
—
—
1.40 (t, 3 H, ОСН2СН3, J = 7.0); 4.00, 4.07 (both s, 3 H each, ОMe); 4.43 (q, 2 H,
ОСН2СН3, J = 7.0); 6.81 (s, 1 H, H(9)); 7.45 (s, 1 H, H(7)); 9.18 (s, 1 H, H(1))
1.39 (t, 3 H, ОСН2СН3, J = 6.9); 4.08, 4.14 (both s, 3 H each, ОMe); 4.42 (q, 2 H,
ОСН2СН3, J = 6.9); 6.87 (d, 1 H, H(9), J = 2.6); 7.29 (d, 1 H, H(7), J = 2.6);
8.67 (s, 1 H, H(2))
10a
3415
1710
1610,
1585
—
—
1.32 (t, 3 H, ОСН2СН3, J = 7.0); 3.91 (s, 3 H, OMe); 4.31 (q, 2 H, ОСН2СН3,
J = 7.0); 6.46 (dd, 1 H, H(5´), J1 = 8.8, J2 = 2.4); 6.60 (d, 1 H, H(3´), J = 2.4);
7.58 (d, 1 H, H(6´), J = 8.8); 7.79 (s, 1 H, H(2)); 10.37 (s, 1 H, ОН);
14.35 (br.s, 1 H, NH)
1.36 (t, 3 H, ОСН2СН3, J = 7.0); 3.85, 3.90 (both s, 3 H each, OMe); 4.36 (q, 2 H,
ОСН2СН3, J = 7.0); 6.09 (s, 1 H, H(5´)); 6.18 (s, 1 H, H(3´)); 7.90 (s, 1 H,
H(2)); 13.38 (br.s, 1 H, ОН); 14.79 (s, 1 H, NH)
2.65 (s, 3 H, Me); 6.30 (br.s, 1 H, ОН); 6.71 (d, 1 H, H(5´), J = 8.9);
6.75 (s, 1 H, H(3´)); 7.70 (d, 1 H, H(6´), J = 8.9); 7.76 (s, 1 H, H(2));
13.28 (br.s, 1 H, NH)
1.35 (t, 3 H, ОСН2СН3, J = 7.1); 2.63 (s, 3 H, Me); 4.36 (q, 2 H, ОСН2СН3,
J = 7.1); 6.75 (dd, 1 H, H(5´), J1 = 8.9, J2 = 2.2); 6.81 (d, 1 H, H(3´), J = 2.2);
7.64 (d, 1 H, H(6´), J = 8.9); 8.30 (s, 1 H, H(2)); 10.20 (br.s, 1 H, ОН);
14.43 (br.s, 1 H, NH)
10b
11a
11b
3430
3400
3280
1710
—
1610
1585
1560
(1340)
1700
1585,
1570
—
11d
3440,
3245
—
1585
2225
2.61 (s, 3 H, Me); 6.69 (dd, 1 H, H(5´), J1 = 9.2, J2 = 1.8); 6.77 (d, 1 H, H(3´),
J = 1.8); 7.69 (d, 1 H, H(6´), J = 9.2); 10.49 (s, 1 H, ОН);
11.30 (br.s, 1 H, NH)
(to be continued)

Reactivity of diazoazoles and azolediazonium salts
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
363
Table 2 (continued)
Comꢀ
pound
IR, ν/cm–1
1H NMR, δ (J/Hz)
NH
C=O
C=N,
CN
N=N (NO2)
12a
12b
3320
—
1640,
1600
1540
(1380)
2.74 (s, 3 H, Me); 7.60 (d, 1 H, H(6´), J = 2.6); 8.23 (dd, 1 H, H(4´), J1 = 2.6,
J2 = 7.4); 8.65 (s, 1 H, H(2)); 9.00 (d, 1 H, H(3´), J = 7.4); 10.01 (br.s, 1 H,
ОН); 13.36 (br.s, 1 H, NH)
1.42 (t, 3 H, ОСН2СН3, J = 7.0); 2.35 (s, 3 H, Me); 4.41 (q, 2 H, ОСН2СН3,
J = 7.0); 6.87 (d, 1 H, H(3´), J = 8.5); 7.18 (dd, 1 H, H(4´), J1 = 1.5, J2 = 8.5);
7.65 (d, 1 H, H(6´), J = 1.5); 7.99 (s, 1 H, H(2)); 11.93 (br.s, 1 H, ОН);
14.15 (br.s, 1 H, NH)
3250
1695
1600,
1570
—
12d
13a
13b
14a
14b
15a
3420,
3235
3430
—
—
—
—
—
—
1590
1590
1600
2230
—
2.59 (s, 3 H, Me); 6.65 (d, 1 H, H(3´), J = 9.0); 7.69 (s, 1 H, H(6´));
7.81 (d, 1 H, H(4´), J = 9.0); 10.64 (s, 1 H, ОН); 12.07 (br.s, 1 H, NH)
3.89 (s, 3 H, OMe); 7.13 (d, 2 H, H(2´), H(6´), J = 8.9); 7.95 (d, 2 H, H(3´),
H(5´), J = 8.9); 8.63 (s, 1 H, H(5)); 14.31 (br.s, 1 H, NН)
3.91 (s, 3 H, OMe); 7.19 (d, 2 H, H(2´), H(6´), J = 8.9); 7.92 (s, 1 H, H(2));
7.94 (d, 2 H, H(3´), H(5´), J = 8.9); 13.24 (br.s, 1 H, NН)
2.31 (s, 3 H, Me); 2.36 (s, 6 Н, 2 Me); 7.03 (s, 2 H, H(3´), H(5´));
8.68 (s, 1 H, H(5)); 14.16 (br.s, 1 H, NН)
3425
3430
3420
—
1565
(1345)
—
1595,
1575
1600
1550
(1340)
—
2.22, 2.32, 2.49 (all s, 3 H each, Me); 7.06 (s, 2 H, H(3´), H(5´));
7.99 (s, 1 H, H(2)); 13.60 (br.s, 1 H, NН)
1605,
1590
1600, 1580
1600,
6.38 (d, 1 H, H(9), J = 2.2); 6.49 (dd, 1 H, H(7), J1 = 9.2, J2 = 2.2);
7.68 (d, 1 H, H(6), J = 9.2); 8.89 (s, 1 H, H(2)); 10.71 (br.s, 1 H, ОН)
3.88 (s, 6 H, OMe); 6.14 (s, 2 H, H(7), H(9)); 8.94 (s, 1 H, H(2))
3.91 (s, 3 H, OMe); 6.51 (d, 1 H, H(9), J = 2.2); 6.58 (dd, 1 H, H(7), J1 = 9.0,
J2 = 2.2); 7.76 (d, 1 H, H(6), J = 9.0); 8.91 (s, 1 H, H(2))
7.49 (m, 3 H, H(3), H(4), H(5)); 8.00 (m, 2 H, H(2), H(6));
14.65 (br.s, 1 H, NH)
2.54 (s, 3 H, Me); 7.33 (d, 2 H, H(3), H(5), J = 9.0); 7.87 (d, 2 H, H(2), H(6),
J = 9.0); 14.46 (br.s, 1 H, NH)
2.35, 2.46 (both s, 3 H each, Me); 7.15—7.22 (m, 2 H, H(3), H(4));
7.42 (s, 1 Н, H(6)); 13.94 (br.s, 1 H, NH)
15b
15c
—
—
—
—
—
—
1585
1580
17a
17b
17c
18a
18b
3450
3430
3445
3440
3435
—
—
—
—
—
2235
2220
2225
1590
1600
1585
1580
1530
(1350)
1545
7.48—7.67 (m, 5 H, Ph); 7.90 (s, 1 H, H(2)); 13.45 (br.s, 1 H, NH)
—
(1350)
5 mL of glacial AcOH. After 3 h, the solvent was evaporated and
the residue was recrystallized from acetone.
appeared (see Table 1). The precipitate was filtered off and
recrystallized from the corresponding solvent.
C. Resorcinol (0.4 g, 3.61 mmol) was added with stirring at
~20 °C to a solution of diazonium salt 2b,c (0.5 g, 2.45 mmol) in
6 М HCl. The mixture was kept for 1—1.5 h and the precipitate
was filtered off and recrystallized from acetone.
D. Resorcinol (0.33 g, 3.01 mmol) was added at ~20 °C to a
solution of diazo compound 1c (0.5 g, 3.01 mmol) in 15 mL of
MeCN. The reaction mixture was kept for 12 days. The solvent
was evaporated in vacuo and the residue was triturated with
ether and filtered. The precipitate was recrystallized from
acetone.
B. 1,3,5ꢀTrimethoxybenzene (0.56 g, 3.3 mmol) or 1,3ꢀdiꢀ
methoxybenzene (0.43 mL, 3.3 mmol) was added to a mixture of
diazonium salts 2a,d (3.0 mmol) in 10 mL of glacial AcOH. The
reaction mixture was kept at 70 °C until the starting compound
disappeared (see Table 1). The precipitate was filtered off and
washed with ether.
Ethyl 5ꢀ(2,4,6ꢀtrimethoxyphenyl)ꢀ (6b) and 5ꢀ(4ꢀhydroxyꢀ
2,6ꢀdimethoxyphenyl)azoimidazoleꢀ4ꢀcarboxylate (10b). Ethyl
5ꢀdiazoimidazoleꢀ4ꢀcarboxylate (1b) (0.5 g, 3.0 mmol) was disꢀ
solved in 5 mL of conc. AcOH, 1,3,5ꢀtrimethoxybenzene (0.56 g,
3.3 mmol) was added, and the mixture was left at ~20 °C for
~18 h. The solvent was evaporated and the dry residue containꢀ
ing compounds 6b and 10b was dissolved in a slight amount
of EtOH and separated by column chromatography
(CHCl3—EtOH, 3 : 1). The yield of compound 6b was 0.62 g
(62%), that of compound 10b was 0.14 g (15%).
4ꢀNitroꢀ5ꢀ(2,4,6ꢀtrimethoxyphenyl)azoimidazole
(6a),
2ꢀ(2,4,6ꢀtrimethoxyphenyl)azoimidazoleꢀ4,5ꢀdicarbonitrile (6d),
4ꢀnitroꢀ5ꢀ(2,4ꢀdimethoxyphenyl)azoimidazole (7a), 2ꢀ(2,4ꢀdiꢀ
methoxyphenyl)azoimidazoleꢀ4,5ꢀdicarbonitrile (7d). A. 1,3,5ꢀTriꢀ
methoxybenzene (0.56 g, 3.3 mmol) or 1,3ꢀdimethoxybenzene
(0.43 mL, 3.3 mmol) was added with stirring at ~20 °C to a
solution of diazo compound 1a or diazonium salt 2d (3.0 mmol)
in 15 mL of CHCl3 or anhydrous MeCN. The reaction mixture
was kept under these conditions until the diazo compound disꢀ
Ethyl 5ꢀ(2ꢀhydroxyꢀ4,6ꢀdimethoxyphenyl)azoimidazoleꢀ4ꢀ
carboxylate (10b). Ethyl 5ꢀdiazoimidazoleꢀcarboxylate (1b)
(0.5 g, 3.0 mmol) was dissolved in 10 mL of dry CHCl3, 1,3,5ꢀtriꢀ

364
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 2, February, 2005
Sadchikova and Mokrushin
methoxybenzene (0.56 g, 3.3 mmol) was added, and the mixture
was kept for 3 h at 60 °C. The solvent was evaporated in vacuo,
the residue was suspended in Et2O, and the yellow precipitate
was filtered off.
4ꢀRꢀ5ꢀ(2,4,6ꢀTrimethoxyphenyl)ꢀ (6b,c) and 4ꢀRꢀ5ꢀ(2,4ꢀdiꢀ
methoxyphenyl)azoimidazoles (7b,c) (general procedure).
1,3,5ꢀTrimethoxybenzene (0.56 g, 3.3 mmol) or 1,3ꢀdimethoxyꢀ
benzene (0.43 mL, 3.3 mmol) was added with stirring at ~20 °C
to a solution of 3 mmol of diazo compound 1b,c (method A) or
diazonium salt 2b,c (method B) in 5 mL of glacial AcOH. The
reaction mixture was kept under these conditions until the reacꢀ
tion was completed (see Table 1), and the precipitate was filꢀ
tered off.
3ꢀ(2,4,6ꢀTrimethoxyphenyl)ꢀ (6e) and 3ꢀ(2,4ꢀdimethoxyꢀ
phenyl)azoꢀ1,2,4ꢀtriazole (7e). Crystalline NaNO2 (0.49 g,
7.14 mmol) was added with vigorous stirring at 0 °C to a solution
of 3ꢀaminoꢀ1,2,4ꢀtriazole (0.5 g, 5.95 mmol) in 3 mL of
50% H2SO4. The reaction mixture was kept for 15 min under
the same conditions, then 1,3,5ꢀtrimethoxybenzene (1.2 g,
7.14 mmol) or 1,3ꢀdimethoxybenzene (0.93 mL, 7.14 mmol)
was added, and the precipitate that formed was filtered off.
Ethyl 5ꢀ(4ꢀhydroxyꢀ2ꢀmethoxyphenyl)azoimidazoleꢀ4ꢀcarbꢀ
oxylate (10a). 1,3ꢀDimethoxybenzene (0.43 mL, 3.3 mmol) was
added dropwise to a solution of diazo compound 1b (0.5 g,
3.0 mmol) in 10 mL of anhydrous CHCl3. The reaction mixture
was kept at 60 °C for several days. The orange precipitate was
filtered off.
stirred solution of 3ꢀaminoꢀ1,2,4ꢀtriazole (0.5 g, 5.95 mmol) in
5 mL of 30% H2SO4. The reaction mixture was kept under the
same conditions for 15 min, and then anisole (0.82 mL,
7.14 mmol) or mesitylene (1.0 mL, 7.14 mmol) was added. The
mixture was kept until the starting diazotriazole disappeared
(see Table 1) and the precipitate was filtered off.
4ꢀNitroimidazoleꢀ5ꢀdiazonium phosphate (2a). Finely ground
sodium nitrite (0.67 g, 9.77 mmol) was added at –10 °C over a
period of 10 min to a vigorously stirred solution of 4ꢀaminoꢀ5ꢀ
nitroimidazole 16 (0.5 g, 3.91 mmol) in 5 mL of concentrated
orthophosphoric acid. The temperature was raised to 0 °C durꢀ
ing 0.5 h and then to +10 °C during 1 h. The mixture was stirred
until the sodium nitrite grains disappeared. The product was not
isolated but used immediately for the reaction with anisole and
mesitylene.
4ꢀNitroꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ (13b) and 4ꢀnitroꢀ5ꢀ(2,4,6ꢀ
trimethylphenyl)azoimidazole (14b). A. Anisole (0.38 mL,
2.34 mmol) or mesitylene (0.33 mL, 2.34 mmol) was added to
diazo solution of yellowꢀgreen salt 2a and the temperature was
raised to 20 °C, the mixture was stirred for 12 or 50 h, respecꢀ
tively and diluted with water, and the precipitate was filtered off
and reprecipitated with water from ethanol.
B. Diazoimidazole 1a (0.5 g, 3.6 mmol) was dissolved in
5 mL of glacial AcOH, then 1 mL of conc. H2SO4 and anisole
(0.5 mL, 4.37 mmol) or mesitylene (0.62 mL, 4.37 mmol) were
added successively at ~20 °C, the mixture kept for 20 or 84 h,
respectively. The precipitate was filtered off and recrystallized
from EtOH.
Benzo[e]imidazoꢀ
(9a,b,e)
and
benzo[e]pyrazoꢀ
lo[5,1ꢀc][1,2,4]triazines (9c,d,f). Azo compound 5b,c, 6b
(method A), 6c, 7c, 8, or 10a,b (method B) (2 mmol) was disꢀ
solved in 10 mL of conc. AcOH and pꢀtoluenesulfonic acid
(0.2 mmol) was added. The reaction mixture was kept at
80—90 °C (see Table 1), twoꢀthird of the solvent was distilled off
in vacuo and the solution was cooled. The precipitate was filꢀ
tered off and recrystallized from EtOH.
4ꢀRꢀ5ꢀ(4ꢀHydroxyꢀ2ꢀmethylphenyl)azoimidazoles 11a,b and
4ꢀRꢀ5ꢀ(5ꢀhydroxyꢀ2ꢀmethylphenyl)azoimidazoles 12a,b (general
procedure). A. mꢀCresol or pꢀcresol (0.35 mL, 3.3 mmol) was
added dropwise to a solution of diazoimidazole 1a,b (3.0 mmol)
in 10 mL of anhydrous CHCl3. The reaction mixture was kept at
~20 °C until the reaction was completed (see Table 1). The
orangeꢀcolored precipitate was filtered off and recrystallized from
a CHCl3—acetone mixture (10 : 1).
B. A solution of diazonium salt 2a,b (3.0 mmol) and mꢀcresol
or pꢀcresol (0.35 mL, 3.3 mmol) in 5 mL of conc. AcOH was
kept at 80—90 °C until the initial diazoimidazole disappeared
(see Table 1). In the case of synthesis of compounds 11a,b, the
orangeꢀcolored precipitate was filtered off and recrystallized from
a CHCl3—acetone mixture (10 : 1). In the synthesis of azo
derivatives 12a,b, the solvent was evaporated in vacuo and the
residue was recrystallized from EtOH.
2ꢀ(4ꢀHydroxyꢀ2ꢀmethylphenyl)ꢀ (11d) and 2ꢀ(5ꢀhydroxyꢀ
2ꢀmethylphenyl)azoimidazoleꢀ4,5ꢀdicarbonitrile (12d). mꢀ or
pꢀCresol (0.36 g, 3.32 mmol) was added with stirring at ~20 °C
to a solution of diazonium salt 2d (0.5 g, 2.77 mmol) in 10 mL of
anhydrous MeCN. The reaction mixture was kept at 80 °C for
1 h and 4 h, respectively. The solvent was evaporated in vacuo
and the residue was recrystallized from EtOH.
8ꢀHydroxybenzo[2,1ꢀe]ꢀ
(15a),
6,8ꢀdimethoxybenꢀ
zo[2,1ꢀe]ꢀ (15b) and 8ꢀmethoxybenzo[2,1ꢀe][1,2,4]triazoꢀ
lo[5,1ꢀc]ꢀasꢀtriazine (15c). An aqueous solution of NaNO2
(0.49 g, 7.14 mmol) was added dropwise at 0 °C to a vigorously
stirred solution of 3ꢀaminoꢀ1,2,4ꢀtriazole (0.5 g, 5.95 mmol) in
5 mL of 30% H2SO4. The reaction mixture was kept under the
same conditions for 15 min, resorcinol (0.79 g, 7.18 mmol) (or
1,3,5ꢀtrimethoxybenzene (1.2 g, 7.14 mmol), or 1,3ꢀdimethoxyꢀ
benzene (0.93 mL, 7.14 mmol)) was added. After 20—60 min,
the precipitate was filtered off.
Synthesis of 2ꢀarylimidazoleꢀ4,5ꢀdicarbonitriles 17a—c and
4ꢀnitroꢀ5ꢀarylimidazoles 18a,b (general procedure). 4,5ꢀDicyanoꢀ
imidazoleꢀ2ꢀdiazonium chloride (2d) or 4ꢀnitroꢀ5ꢀdiazoimidꢀ
azole (1a) was suspended in benzene, toluene, or pꢀxylenе. The
reaction mixture was kept at about 60—70 °C (for 2d) or at the
arene boiling point (for 1a) until the starting diazo compound
disappeared (see Table 1). The solvent was evaporated in vacuo
and the residue was triturated with tertꢀbutyl methyl ether and
crystallized from acetone.
MS 18b, m/z (Irel (%)): 204 (5.57); 203 (40.32); 183 (35.81);
103 (37.74); 92 (38.79); 91 (100); 77 (45.68); 65 (36.71).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 04ꢀ03ꢀ
96121a).
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Reactivity of diazoazoles and azolediazonium salts
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Received December 29, 2003;
in revised form June 25, 2004