Triple equilibrium in n′-aryl-n-tosyldiazomalonimidolates, 1-tosyl-1,2,3-triazol-5-olates, and 1-aryl-1,2,3-triazol-5-olates

Article abstract of DOI:10.1023/A:1023756005530

A series of 1-tosyl-substituted 4-arylcarbamoyl-1,2,3-triazol-2-olates, which can undergo rearrangement to isomeric 1-aryl-4-tosylcarbamoyl-1,2,3-triazol-5-olates and N-tosyl-N′-aryldiazomalonimidolates, were synthesized. An equilibrium between these comp

Full text of DOI:10.1023/A:1023756005530

Chemistry of Heterocyclic Compounds, Vol. 39, No. 2, 2003
TRIPLE EQUILIBRIUM IN N'-ARYL-
N-TOSYLDIAZOMALONIMIDOLATES,
1-TOSYL-1,2,3-TRIAZOL-5-OLATES,
AND 1-ARYL-1,2,3-TRIAZOL-5-OLATES
Yu. Yu. Morzherin, Yu. A. Rozin, E. A. Savel'eva, and V. A. Bakulev
A
series of 1-tosyl-substituted 4-arylcarbamoyl-1,2,3-triazol-2-olates, which can undergo
rearrangement to isomeric 1-aryl-4-tosylcarbamoyl-1,2,3-triazol-5-olates and N-tosyl-N'-
aryldiazomalonimidolates, were synthesized. An equilibrium between these compounds is observed in
solutions in DMSO. The introduction of an electron-withdrawing substituent into the aryl residue
increases the stability of the 1-tosyl-1,2,3-triazoles but reduces the stability of the 1-aryl-1,2,3-triazoles.
π-Donating substituents increase the stability of the open-chain structure.
Keywords: diazo compounds, sulfonamides, 1,2,3-triazoles, diazo transfer reaction, equilibrium.
The chemistry of sulfonamides has been the subject of much attention in the literature [1, 2]. The
constant interest in compounds of this class can be explained by the fact that linear and cyclic compounds
containing sulfonamide fragments have a broad spectrum of biological activity: antiulcerous [3], diuretic [4],
fungicidal, insecticidal, herbicidal, antibacterial [5], inhibition of enzymes [6]. At the same time the reactivity of
the N-sulfonyl derivatives of diazoacetamide [7], a knowledge of which is essential for the development of
methods for the directed synthesis of azoles containing a sulfonamide group, has not so far been investigated.
Earlier [8] we showed that the reaction of the N-arylsulfonylamides of malonic acid with
benzenesulfonyl azide in the presence of sodium ethoxide leads to the formation of 1-sulfonyl-1,2,3-triazol-5-
olates. The aim of the present work was to synthesize the N-tosyl derivatives of diazomalonamides 1 and
investigate their ring–chain isomerism.
Compounds 1 were synthesized by the method described in [8], starting from derivatives of the
monotosylamide of malonic acid by the "diazo transfer" reaction. In the case of "diazo transfer" in
unsymmetrically substituted malonodiamides 2a-g a complex pattern of behavior is possible; here cyclization is
probable both at the N atom of the sulfonamide group with the formation of 1-tosyl-1,2,3-triazoles 3 and at the
N atom of the anilide function with the formation of 1-aryl-1,2,3-triazoles 4 [9]. However, during "diazo
1
transfer" the individual 1-tosyltriazoles 3a-g were isolated. In the H NMR spectra of these compounds
(Table 1) the signal of the methyl group was observed at 2.39 ppm, which is typical of the signals of the tosyl
function at position 1 of the triazole ring [8]. For compounds 3a,b the signal of the protons of the methoxy
1
group in the H NMR spectrum appears at 3.74-3.76 ppm, i.e., in an upfield region from the protons of the
anisidine function at position 1 of the triazole ring.
__________________________________________________________________________________________
Urals State Technical University, Ekaterinburg 620002, Russia; e-mail: morjerine@htf.ustu.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 196-201, February, 2003. Original article
submitted May 12, 2000.
168
0009-3122/03/3902-0168$25.00©2003 Plenum Publishing Corporation

O
O
O
O
Tos
Tos
R
N
H
N
H
N
H
OH
2a–g
ONa
ONa
Tos
+
+
N
N
R
Na
Na
Tos
∆
N
O
O
N
N
N
R
ONa
ONa
N
N
N
N
N
R
Tos
1a–2g
4a–g
3a–g
1–4 a R = 4-MeOC6H4, b R = 2-MeOC6H4, c R = Ph, d R = 3-O2NC6H4, e R = 4-BrC6H4,
f R = 2,4,6-Cl3C6H2, g R = CH2Ph
Individual products 4a-g, which did not coincide chromatographically with the initial compounds, were
also isolated when the tosyltriazoles 3a-g were boiled for a long time in aqueous solutions. The 1H NMR spectra
of these compounds contained signals for the methyl group of the tosyl function at 2.32 ppm, which is typical of
the position of the tosyl fragment in the carboxamide fragment [8]. For compounds 4a,b a downfield shift of
0.12 ppm (3.86-3.90 ppm) is also observed for the signals of the protons of the methoxy groups in the aromatic
fragment, indicating that the aryl residue is at position 1 of the triazole ring [8]. The absorption band
characteristic of the diazo group does not appear in the IR spectrum. On the basis of these data the structure of
isomeric 1-aryltriazoles 4a,b, containing a sulfonyl group in the carboxamide function at position 4 of the
heterocycle, was assigned to these compounds.
During the recrystallization of compounds 3a-g from ethanol or carbon tetrachloride the diazo
compounds 1a-g were isolated. The signals for the protons of the methyl group in the tosyl function at 2.32 ppm
and of the methoxy group (in the anilide residue for compounds 1a,b) at 3.76-3.75 ppm were observed in the
1H NMR spectra, and this is typical of aryl and tosyl fragments located in the carboxamide groups and not at
position 1 of the triazole ring [8]. A band for the vibrations of the diazo group was observed in the IR spectrum
at 2130 cm-1.
The appearance, according to TLC, of 1-aryltriazoles 4a-g and diazomalonodiimidolates 1a-g in
addition to the initial triazole 3a-g was observed when the 1-sulfonyltriazoles 3a-g were kept in DMSO solution
for a long time at room temperature. It was not possible to separate the mixture. Similar results were obtained
with solutions of compounds 4a-g and 1a-g. Table 2 gives data on the composition of the equilibrium mixtures
of compounds 1, 3, and 4, which were determined from the integral intensities of the signals for the protons of
the methyl group and aromatic ring of the given compounds in solution in DMSO-d6. The composition of the
mixtures obtained from compounds 1 agreed within the experimental error limits (2-5%) with the composition
of the mixtures obtained from compounds 3 and 4. During analysis of Table 2 it is possible to arrange the
substituents in the aryl group in the following order according to the effect on the stability of the compounds:
1-tosyl-1,2,3-triazole
3-O2NC6H4 >> 2-MeOC6H4 > 4-BrC6H4 > Ph > 4-MeOC6H4 > C6H2Cl3 >> Bn
1-aryl-1,2,3-triazole
Bn >> 4-MeOC6H4 > Ph > 4-BrC6H4 >> 3-O2NC6H4~ 2-MeOC6H4 ~ C6H2Cl3
diazomalonamide
C6H3Cl3 > 2-MeOC6H4 > 4-MeOC6H4 > 4-BrC6H4 > Ph >> 3-O2NC6H4 ~ Bn
169

TABLE 1. The 1H NMR Spectra of Compounds 1, 3, and 4
Com-
Chemical shift, δ, ppm, and multiplicity of the signals in DMSO-d6
pound
7.82 (2H, d, ArH); 7.65 (2H, d, ArH); 7.40 (2H, d, ArH); 6.91 (2H, d, ArH);
3.74 (3H, s, ArOCH3); 2.32 (3H, s, ArCH3)
1a
1b
1c
1d
1e
8.30 (1H, ddd, ArH); 7.83 (2H, d, ArH); 7.38 (2H, d, ArH); 7.18 (1H, ddd, ArH);
7.13 (1H, ddd, ArH); 7.02 (1H, ddd, ArH); 3.76 (3H, s, OCH3); 2.32 (3H, s, ArCH3)
7.55-7.66 (2H, m, Ph); 7.30-7.40 (3H, m, Ph); 7.34 (2H, d, ArH); 7.17 (2H, d, ArH);
2.32 (3H, s, ArCH3)
9.14 (1H, dd, ArH); 8.48 (1H, ddd, ArH); 8.00 (1H, ddd, ArH); 7.77 (2H, d, ArH);
7.70 (1H, dd, ArH); 7.19 (2H, d, ArH); 2.32 (3H, s, ArCH3)
8.05 (2H, d, ArH); 7.60 (2H, d, ArH); 7.80 (2H, d, ArH); 7.20 (2H, d, ArH);
2.32 (3H, s, ArCH3)
7.68 (2H, d, ArH); 7.58 (2H, s, ArH); 7.21 (2H, d, ArH); 2.32 (3H, s, ArCH3)
1f
1g
7.80 (2H, d, ArH); 7.38 (5H, s, Ph); 7.20 (2H, d, ArH); 5.35 (2H, s, PhCH2);
2.32 (3H, s, ArCH3)
7.82 (2H, d, ArH); 7.68 (2H, d, ArH); 7.32 (2H, d, ArH); 6.85 (2H, d, ArH);
3.73 (3H, s, ArOCH3); 2.36 (3H, s, ArCH3)
3a
3b
3c
3d
3e
8.27 (1H, ddd, ArH); 7.87 (2H, d, ArH); 7.30 (2H, d, ArH); 7.18 (1H, ddd, ArH);
7.13 (1H, ddd, ArH); 7.02 (1H, ddd, ArH); 3.72 (3H, s, OCH3); 2.36 (3H, s, ArCH3)
7.60-7.70 (2H, m, Ph); 7.20-7.30 (3H, m, Ph); 7.38 (2H, d, ArH); 7.13 (2H, d, ArH);
2.35 (3H, s, ArCH3)
9.15 (1H, dd, ArH); 8.39 (1H, ddd, ArH); 8.01 (1H, ddd, ArH); 7.78 (2H, d, ArH);
7.70 (1H, dd, ArH); 7.20 (2H, d, ArH); 2.39 (3H, s, ArCH3)
8.06 (2H, d, ArH); 7.58 (2H, d, ArH); 7.79 (2H, d, ArH); 7.16 (2H, d, ArH);
2.36 (3H, s, ArCH3)
7.83 (2H, d, ArH); 7.70 (2H, s, ArH); 7.28 (2H, d, ArH); 2.35 (3H, s, ArCH3)
3f
3g
7.85 (2H, d, ArH); 7.30 (5H, s, Ph); 7.29 (2H, d, ArH); 5.36 (2H, s, PhCH2);
2.36 (3H, s, ArCH3)
7.84 (2H, d, ArH); 7.63 (2H, d, ArH); 7.36 (2H, d, ArH); 6.98 (2H, d, ArH);
3.84 (3H, s, ArOCH3); 2.32 (3H, s, ArCH3)
4a
4b
4c
4d
4e
8.28 (1H, ddd, ArH); 7.84 (2H, d, ArH); 7.38 (2H, d, ArH); 7.18 (1H, ddd, ArH);
7.14 (1H, ddd, ArH); 7.02 (1H, ddd, ArH); 3.90 (3H, s, OCH3); 2.32 (3H, s, ArCH3)
7.58-7.65 (2H, m, Ph); 7.30-7.40 (3H, m, Ph); 7.34 (2H, d, ArH); 7.15 (2H, d, ArH);
2.32 (3H, s, ArCH3)
9.15 (1H, dd, ArH); 8.48 (1H, ddd, ArH); 8.02 (1H, ddd, ArH); 7.79 (2H, d, ArH);
7.70 (1H, dd, ArH); 7.20 (2H, d, ArH); 2.32 (3H, s, ArCH3)
8.07 (2H, d, ArH); 7.57 (2H, d, ArH); 7.78 (2H, d, ArH); 7.18 (2H, d, ArH);
2.32 (3H, s, ArCH3)
7.67 (2H, s, ArH); 7.64 (2H, d, ArH); 7.16 (2H, d, ArH); 2.32 (3H, s, ArCH3)
4f
4g
7.70 (2H, d, ArH); 7.55 (5H, s, Ph); 7.21 (2H, d, ArH); 5.60 (2H, s, PhCH2);
2.32 (3H, s, ArCH3)
TABLE 2. The Composition of the Mixture of Triazoles 3 and 4 and the
Diazo Compound 1 in DMSO-d6
Content in mixture, %
Compound
3
4
1
16
42
30
99
35
10
0.2
42
<0.1
35
42
58
35
0.2
40
90
0.2
a
b
c
d
e
f
0.8
25
<0.1
99.6
g
170

As seen from these series, the effect on the stability of the isomers differs: accepting substituents
increase the stability of 1-tosyl-1,2,3-triazole 3 but reduce the stability of 1-aryl-1,2,3-triazoles 4, while
π-donating substituents increase the stability of the open-chain structure 1. ortho-Substituted aryls destabilize
the 1-aryl-1,2,3-triazoles 4.
TABLE 3. The Characteristics of Compounds 1-4
Found, %
——————
Com-
pound
Empirical
formula
Calculated, %
mp, °С
Yield, %
N
S
11.78
11.96
6.85
6.85
>200 dec.
>200 dec.
>200 dec.
>200 dec.
>200 dec.
>200 dec.
>200 dec.
179-181
91
78
85
82
68
88
78
68
72
65
53
58
72
82
88
92
91
96
84
83
77
82
88
87
86
89
90
92
1a
1b
1c
1d
1e
1f
C17H14N4Na2O5S·2Н2О
C17H14N4Na2O5S·2Н2О
12.03
6.35
11.96
6.85
C16H12N4Na2O4S·2Н2О
C16H11N5Na2O6S·2Н2О
C16H11BrN4Na2O4S·2Н2О
C16H9Cl3N4Na2O4S·2Н2О
C17H14N4Na2O4S·2Н2О
C17H18N2O5S
12.98
12.78
7.12
7.31
14.55
6.35
14.49
6.63
10.82
10.83
6.13
6.20
10.08
5.55
10.33
5.92
12.36
12.38
6.87
7.09
1g
2a
2b
2c
2d
2e
2f
7.68
8.97
7.73
8.85
C17H18N2O5S
8.30
7.73
9.17
8.85
183-187
C16H16N2O4S
8.31
9.57
186
8.43
9.65
C16H15N3O6S
11.35
11.13
8.22
8.50
208-212
C16H15BrN2O4S
7.10
7.59
210-212
6.81
7.80
C16H13Cl3N2O4S
6.93
6.43
7.18
7.36
210-213
C17H18N2O4S
8.00
9.33
159-162
2g
3a
3b
3c
3d
3e
3f
8.09
9.26
C17H14N4Na2O5S·2Н2О
C17H14N4Na2O5S·2Н2О
C16H12N4Na2O4S·2Н2О
C16H11N5Na2O6S·2Н2О
C16H11BrN4Na2O4S·2Н2О
C16H9Cl3N4Na2O4S·2Н2О
C17H14N4Na2O4S·2Н2О
C17H14N4Na2O5S·2Н2О
C17H14N4Na2O5S·2Н2О
C16H12N4Na2O4S·2Н2О
C16H11N5Na2O6S·2Н2О
C16H11BrN4Na2O4S·2Н2О
C16H9Cl3N4Na2O4S·2Н2О
C17H14N4Na2O4S·2Н2О
11.65
11.96
6.75
6.85
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
11.78
6.33
11.96
6.85
12.50
12.78
7.03
7.31
14.23
6.33
14.49
6.63
10.38
10.83
6.05
6.20
10.21
5.33
10.33
5.92
12.30
12.38
7.11
7.09
3g
4a
4b
4c
4d
4e
4f
12.01
6.33
11.96
6.85
11.66
11.96
6.99
6.85
13.09
7.00
12.78
7.31
14.12
14.49
6.75
6.63
10.53
6.10
10.83
6.20
10.00
10.33
5.62
5.92
12.18
6.85
4g
12.38
7.09
171

O
O
PhCH2N3
PhSO2
12
Et
4g
3g
1g
N
H
O
5
In order to confirm the structure of the compounds we tried to synthesize compound 4g by an alternative
method by the reaction of malonamide 5 with benzyl azide. However, the reaction (boiling in an alcohol
solution of sodium ethoxide) resulted in the isolation of the rearrangement product 3g, which according to
spectral data and TLC and elemental analysis coincided with previously obtained compound.
Thus, it was demonstrated as a result of the work that 1-tosyl-1,2,3-triazol-5-olates 3 are labile
compounds. With heat or during prolonged standing in solution they isomerize to diazomalonimidolates 1 and
4-tosylcarbamoyltriazol-5-olates 4. Here the stability of the isomers is determined to a large degree by the
electronic and steric characteristics of the substituents in the anilide residue.
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker 250 instrument at 250 MHz. The IR spectra were
recorded on a UR-25 spectrometer for tablets with potassium bromide. The reactions and the purity of the
products were monitored by TLC on Silufol UV-254 plates in chloroform, 3:1 ethyl acetate–hexane, 9:1
chloroform–ethanol, and 60:11:1 chloroform–ethanol–ammonia (25%). The melting points were not corrected.
N-Aryl-N'-arylsulfonylmalonamides (2a-g). General Procedure. To
a
solution of the
monotosylamide (0.01 mol) of malonic acid and the respective anilide (0.01 mol) in dry dioxane (15 ml) we
added in portions with stirring at room temperature dicyclohexylcarbodiimide (2.37 g, 11.5 mmol). The mixture
was stirred for 10-15 h. The isolated dicyclohexylurea was filtered off and washed with dioxane (2 ml). The
obtained solution was acidified to pH 2-3 with 1 N hydrochloric acid and diluted with water (60 ml). The oil
that separated initially gradually began to crystallize. The compound was filtered off and reprecipitated from
aqueous ammonia (10%) by the addition of 1 N hydrochloric acid to pH 2-3 and was then recrystallized from
aqueous dioxane.
Disodium 4-N-Arylcarbimidoyl-1-tosyl-1,2,3-triazol-5-ate (3a-g). General Procedure. To a solution
or suspension of the malonamide 2a-g (5 mmol) in absolute ethanol (20 ml) with stirring at room temperature
we added a solution of sodium (0.23 g, 10 mmol) in absolute ethanol (5 ml) and then benzenesulfonyl azide
(1.0 g, 5.5 mmol). The mixture was left at room temperature for 24 h. The precipitate was filtered off and
washed with ethanol (2 ml). The product was dried over phosphorus pentoxide under vacuum.
Disodium N-Aryl-N'-tosyldiazomalonimidolate (1a-g). General Procedure. The malonamide 3a-g
(5 mmol) was boiled in absolute ethanol (20 ml) or carbon tetrachloride for 4-8 h. The mixture was cooled, and
the precipitate was filtered off. The product was dried over phosphorus pentoxide under vacuum.
Disodium 1-Aryl-4-N-tosylcarbimidoyl-1,2,3-triazol-5-ate (4a-g). General Procedure. To a solution
or suspension of the malonamide 3a-g (5 mmol) in absolute ethanol (20 ml) with stirring at room temperature
we added a solution of sodium (0.23 g, 10 mmol) in absolute ethanol (5 ml) and then benzenesulfonyl azide
(1.0 g, 5.5 mmol). The mixture was left for 24 h. The reaction mixture was evaporated at reduced pressure, and
water (15 ml) was added. The benzenesulfonamide was filtered off, and the filtrate was boiled for 2-3 h with a
reflux condenser. The reaction mixture was evaporated to dryness at reduced pressure. The product was dried
over phosphorus pentoxide under vacuum.
The work was carried out with financial support from the Russian Foundation for Basic Research
(grant 98-03-33045-a).
172

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