Synthesis and properties of 1-arylsulfonyl-1,2,3-triazol-5-olates

Article abstract of DOI:10.1023/A:1011648303788

A series of 1-arylsulfonyl-4-carbamoyl-1,2,3-triazol-5-olates has been synthesized. The cyclization of diazoacetamides by the action of base has been shown to be reversible for the first time. 1-Arylsulfonyl-1,2,3-triazol-5-olates undergo rearrangement upon heating to give isomeric N-sulfonylcarbamoyldiazoacetimidolates. An equilibrium exists between these isomers in DMSO solution, which is shifted toward the acyclic derivative.

Full text of DOI:10.1023/A:1011648303788

Chemistry of Heterocyclic Compounds, Vol. 37, No. 5, 2001
SYNTHESIS AND PROPERTIES
OF 1-ARYLSULFONYL-
1,2,3-TRIAZOL-5-OLATES
Yu. Yu. Morzherin, Yu. A. Rozin, E. A. Vorob'eva, and V. A. Bakulev
A series of 1-arylsulfonyl-4-carbamoyl-1,2,3-triazol-5-olates has been synthesized. The cyclization of
diazoacetamides by the action of base has been shown to be reversible for the first time. 1-Arylsulfonyl-
1,2,3-triazol-5-olates
undergo
rearrangement
upon
heating
to
give
isomeric
N-sulfonylcarbamoyldiazoacetimidolates. An equilibrium exists between these isomers in DMSO
solution, which is shifted toward the acyclic derivative.
Keywords: diazomalonimidolates, ring–chain isomerization, diazo transfer reaction, thermodynamic
stability.
The chemistry of aliphatic diazo compounds has been studied intensively during the past few decades
[1-4]. Special interest among these compounds is found for diazoalkanes containing an α-carbamoyl group.
These derivatives have been used to synthesize 1,2,3-triazoles and 1,2,3-thiadiazoles, which display antitumor,
antiviral, and anti-inflammatory activity [5]. On the other hand, there have been no studies of the reactivity of
N-sulfonyldiazoacetamides required for using these compounds in the synthesis of azoles [6].
R2
O
O
O
N
ArSO2
R1
R1
OH
N
N
N
H
N
N2
R2
N
SO2Ar
2
1
We have already shown that the reaction of amides of malonic acid with benzenesulfonyldiazide in the
presence of sodium ethylate leads to highly reactive and unstable diazoimidolates, which cyclize irreversibly to
give 1,2,3-triazol-5-olates [7, 8]. We have also established that 5-hydroxy-1,2,3-triazoles obtained upon
acidification, readily rearrange to give isomeric triazoles and diazo compounds.
In the present work, we synthesized N-sulfonyldiazomalondiamides 1 and studied the intramolecular
cyclization to give sulfonyl derivatives of 1,2,3-triazoles 2.
__________________________________________________________________________________________
Ural State Technical University, 620002 Yekaterinburg, Russia; e-mail: morjerine@htf.ustu.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 612-618, May, 2001. Original article
submitted May 18, 1999.
560
0009-3122/01/3705-0560$25.00©2001 Plenum Publishing Corporation

O
O
O
O
O
O
ArSO2
ArSO2
Et
ArSO2
R1
N
H
OH
N
H
O
N
H
N
R2
4a,b
5a–c
3a,b
R1
+
O
Na
ArSO2
O
O
N
R1
+
R2
ONa
N
N
N
N
R2
N2
N
+
H
H
SO2Ar
7a,c
O
O
ArSO2
R1
6a–c
N
H
N
R2
N2
1a–c
3, 4 a Ar = Ph, b C6H4Me-4
1, 5
a
b
c
6, 7
a
b
c
Ar
R1
R2
C6H4Me-4
SO2C6H4Me-4
H
C6H4Me-4
C6H4NO2-4
Me
Ph
Ar
C6H4Me-4
SO2C6H4NO2-4 C6H4NO2-4 C6H4 NO2-4
Na Me Me
C6H4Me-4
Ph
C6H4 NO2-4 R1
Me
R2
These compounds were obtained through the following scheme. The reaction of arylsulfonylamides with
the acid chloride of the monoethyl ester of malonic acid gave esters of 2-(N-arylsulfonylcarbamoyl)acetic acid
3a,b, which were hydrolyzed to give the corresponding acids 4a,b. The reaction of these acids with amines in
the presence of dicyclohexylcarbodiimide gave amides 5a-c. The diazo transfer reaction [10] with 5a-c gave
sodium salts of triazoles 6a-c in high yield. This reaction requires two equivalents of sodium ethylate and does
1
not proceed with only one equivalent of base. The H NMR spectrum of 6a shows signals for the aromatic
protons as doublets at 7.85, 7.70, 7.29, and 7.22 ppm and three-proton singlets at 2.36 and 2.32 ppm, which
were assigned to the protons of the tosyl groups at N(1) of the triazole ring and in the carboxamide group,
respectively. The treatment of an aqueous solution of triazole 6a with 1 N hydrochloric acid gave a compound
with two-proton doublets for aromatic protons at 7.71 and 7.22 ppm and a three-proton singlet at 2.32 ppm. The
IR spectrum of this product, in contrast to the spectrum of 6a, has a band at 2120 cm-1, corresponding to diazo
group stretching. Hence, this compound was identified as N,N'-disulfonyldiazomalondiamide 1a.
These reactions proceed similarly for malondiamides 5b,c, which have two substituents at the nitrogen
1
atom of one of the amide functions. The H NMR spectrum of 1-sulfonyltriazole 6b shows a methyl group
singlet at 2.36 ppm, while the corresponding signal for diazo compound 1b is found at 2.34 ppm. The IR
spectrum of 1b has a diazo group stretching band at 2120 cm-1.
In an attempt to recrystallize 6a-c from carbon tetrachloride or ethanol, we isolated compounds with
thin-layer chromatographic data different from the starting compounds. The IR spectra of these new compounds
1
showed a diazo group stretching band at 2120 cm-1. These data and the H NMR spectra of these compounds
(see Table 1) indicate that these compounds are diazo compounds 7a-c.
Thus, we have shown that sodium 1-sulfonyl-1,2,3-triazol-5-olates 6a-c may rearrange to open-chain
isomers, diazoimidolates 7. An equilibrium is established between the open-chain and ring forms for triazoles
6a-c upon standing in DMSO-d6 for 30 min with predominance of the open-chain isomers 7a-c (see Table 2).
Analogously, an equilibrium was established for solutions of 7a-c in DMSO-d6. The isomer ratio in both cases
was the same within experimental error.
561

TABLE 1. 1H NMR Spectra of Compounds Synthesized
Com-
Chemical shift and multiplicity of signals in the 1H NMR spectra (DMSO-d6), δ, ppm
pound
12.16 (2H, br. s, NH); 7.77 (4H, d, ArH); 7.41 (4H, d, ArH); 3.25 (2H, s, CH2);
2.40 (6H, s, CH3)
12.6 (1H, br. s, NH); 9.12 (H, s, NH); 8.00 (2H, d, ArH); 7.56 (2H, d, ArH);
7.40 (2H, d, ArH); 7.20 (2H, d, ArH); 3.65 (2H, s, CH2); 3.22 (3H, s, NCH3);
2.32 (3H, s, ArCH3)
5a
5b
8.00 (2H, d, ArH); 7.58-7.65 (2H, m, Ph); 7.42 (2H, d, ArH); 7.30-7.40 (3H, m, Ph);
5c
6a
6b
6c
3.32 (2H, s, CH2); 3.21 (3H, s, NCH3)
7.85 (2H, d, ArH); 7.70 (2H, d, ArH); 7.29 (2H, d, ArH); 7.22 (2H, d, ArH);
2.364 (3H, s, ArCH3); 2.24 (3H, s, ArCH3)
8.08 (2H, d, ArH); 7.67 (2H, d, ArH); 7.53 (2H, d, ArH); 7.23 (2H, d, ArH);
3.22 (3H, s, NCH3); 2.36 (3H, s, ArCH3)
8.08 (2H, d, ArH); 7.60-7.70 (2H, m, Ph); 7.54 (2H, d, ArH); 7.30-7.40 (3H, m, Ph);
3.215 (3H, s, NCH3)
7.70 (2H, d, ArH); 7.21 (2H, d, ArH); 2.316 (3H, s, ArCH3)
7a
7b
8.01 (2H, d, ArH); 7.60 (2H, d, ArH); 7.47 (2H, d, ArH); 7.20 (2H, d, ArH);
3.22 (3H, s, NCH3); 2.33 (3H, s, ArCH3)
8.00 (2H, d, ArH); 7.58-7.65 (2H, m, Ph); 7.50 (2H, d, ArH); 7.30-7.40 (3H, m, Ph);
3.215 (3H, s, NCH3)
7c
9a
9b
11.4 (2Н, br. s, NH); 7.62 (4H, d, ArH); 7.12 (4H, d, ArH); 6.92 (1H, br. s, NH);
6.45 (1H, br. s, NH); 2.32 (6H, s, ArCH3)
11.8 (2Н, br. s, NH); 8.00 (2H, d, ArH); 7.56 (2H, d, ArH); 7.45 (2H, d, ArH);
7.20 (2H, d, ArH); 6.90 (1Н, br. s, NH); 5.88 (1Н, br. s, NH); 3.22 (3H, s, NCH3);
2.33 (3H, s, ArCH3)
12.1 (2Н, br. s, NH); 8.00 (2H, d, ArH); 7.60-7.80 (2H, m, Ph); 7.50 (2H, d, ArH);
9c
7.30-7.40 (3H, m, Ph); 6.44 (1Н, br. s, NH); 6.05 (1Н, br. s, NH), 3.25 (3H, s, NCH3)
7.75 (2H, d, ArH); 7.42 (2H, d, ArH); 3.14 (6H, s, 2 CH3); 2.39 (6H, s, 2 CH3)
10a
10b
8.21 (2H, d, ArH); 7.76 (2H, d, ArH); 7.57 (2H, d, ArH); 7.42 (2H, d, ArH);
3.26 (3H, s, CH3); 3.15 (3H, s, CH3); 2.41 (3H, s, CH3)
8.22 (2H, d, ArH); 7.50-7.93 (7H, m, ArH); 3.26 (3H, s, CH3); 3.19 (3H, s, CH3)
10c
TABLE 2. Equilibrium Mixtures of Triazoles 6a-c and Diazo Compounds
1
7a-c Determined from the Integral Intensities in the H NMR Spectra in
DMSO-d6
Content in mixture, %
Compound
6
7
15
5
6
85
95
94
a
b
c
The liberation of nitrogen was noted upon maintaining solutions of diazo compounds 1a-c in DMSO-d6
1
but the shape of the H NMR spectrum did not change. The cyclization to 1-sulfonyl-1,2,3-triazole presumably
does not occur in this case, but rather decomposition of the diazo compounds to corresponding ketones 8a-c,
which is similar to previously reported behavior [11, 12]. In order to check this hypothesis, solutions of diazo
compounds 1a,b in DMSO-d6 were heated at 85°C and then treated with aqueous hydrazine hydrate. IR and
1H NMR spectroscopy and elemental analysis indicated that the products isolated were hydrazones 9a,b.
562

TABLE 3. Physicochemical Characteristics of Compounds Synthesized
Found, %
——————
Compound
Empirical formula
mp, °C
Yield, %
Calculated, %
N
S
C17H16N4O6S2
12.45
12.84
14.30
14.69
202-208
186-189
215-217
83-85
89
92
95
70
75
75
83
70
65
63
63
68
62
81
83
79
72
68
75
59
71
58
1a
1b
1c
C17H15N5O6S
16.50
7.32
16.78
7.68
C16H13N5O6S
17.03
17.36
7.48
7.95
C11H13NO5S
5.69
12.12
3a
3b
4a
4b
5a
5b
5c
5.16
11.82
C12H15NO5S
5.15
4.91
11.85
11.24
97-98
C9H9NO5S
6.10
12.97
138-139
137-140
136-140
156-158
140-141
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
>250 dec.
232-233
248-249
236-238
132-134
197-198
126-128
5.76
13.18
C10H11NO5S
5.67
5.44
12.12
12.46
C17H18N2O6S2
6.92
15.42
6.82
15.62
C17H17N3O6S
10.62
10.74
8.13
8.19
C16H15N3O6S
11.35
8.47
11.13
8.50
C17H14N4Na2O6S2·2Н2О
C17H14N5NaO6S·2Н2О
C16H12N5NaO6S·2Н2О
C17H14N4Na2O6S2·2Н2О
C17H14N5NaO6S·2Н2О
C16H12N5NaO6S·2Н2О
C17H18N4O6S2·Н2О
C17H17N5O6S·Н2О
C16H15N5O6S·Н2О
C19H20N4O6S2
10.15
10.85
12.13
12.42
6a
6b
6c
14.32
6.41
14.73
6.74
15.00
15.18
6.75
6.95
10.58
12.21
7a
7b
7c
10.85
12.42
14.31
14.73
6.58
6.74
14.75
6.54
15.18
6.95
12.40
12.27
13.88
14.05
9a
9b
9c
15.78
7.05
16.01
7.33
16.45
16.54
7.35
7.57
12.06
13.49
10a
10b
10c
12.06
13.81
C18H17N5O6S·H2O
C17H15N5O6S·H2O
—
—
7.42
7.13
7.49
7.36
O
O
O
O
O
O
ArSO2
R
ArSO2
R
ArSO2
R
N
H
H2N
N
N
H
N
N
H
N
R1
R1
N
9a–c
R1
N2
O
8a–c
1a–c
8, 9
a
b
c
Ar
C6H4Me-4
SO2C6H4Me-4 C6H4NO2-4
Me
C6H4Me-4
Ph
R
C6H4NO2-4
Me
R1
H
563

In order to check the structure of heterocycles 6a-c, the methyl derivatives of these compounds were
synthesized. Thus, the reaction of 6a with methyl iodide gave a compound, whose 1H NMR spectrum displayed
four-proton doublets at 7.75 and 7.42 ppm and six-proton singlets at 3.14 and 2.39 ppm. The IR spectrum of this
product had a carbonyl group stretching band at 1703 cm-1 but lacked the diazo group stretching band.
Na+
O
N
O
_
N
N
O
O
R2
S
N
S
N
ONa
O
O
N
N
Me
Me
Me
Me
O
6a
N
S
O
N+
O
O
O
O
N
N
N
N
Me
ONa
R1
O
S
O
10a–c
6b,c
10 a R1 = Me, R2 = Ts; b R1 = Me, R2 = C6H4NO2-4; c R1 = H, R2 = C6H4NO2-4
R1
These spectral data indicated that methylation occurred at the carbamoyl nitrogen group and N(2) in the
triazole ring. If the reaction had occurred at the oxygen atom and N(3), we would have expected compounds, for
which the signal of the OCH3 or N+CH3 group would be observed downfield in the vicinity of 4 ppm [7]. The
reaction of 6b,c with an excess of methyl iodide gave compounds identified as 2-methyl-1-sulfonyl-1,2,3-
triazolidin-5-ones 10b,c as indicated by the 1H NMR, IR, and mass spectra.
Thus, the cyclization of N-arylsulfonyldiazoacetamides by the action of bases leads to sodium
1-arylsulfonyl-1,2,3-triazole-5-olates. This reaction is estimated to be reversible and the triazolates isomerize to
diazomalonimidolates in solution upon heating or prolonged maintenance. The acylic isomer is more stable.
5-Hydroxy-1-arylsulfonyl-1,2,3-triazoles, formed in the reaction of 1-arylsulfonyl-1,2,3-triazol-5-olates with
acid, rearrange to diazomalonamides, which decompose in DMSO solution to give the corresponding ketones.
EXPERIMENTAL
1
The H NMR spectra were recorded on Bruker WR-80 and Bruker 250 spectrometers with TMS as the
internal standard. The IR spectra were taken on an IR-75 spectrometer in KBr pellets. The course of the
reactions and purity of the products were monitored by thin-layer chromatography on Silufol UV-254 plates
with chloroform, 3:1 ethyl acetate–hexane, 9:1 chloroform–ethanol, and 60:11:1 chloroform–ethanol–25% aq.
ammonia as the eluents. The melting points were not corrected.
Monoethyl Ester of N-Phenylsulfonylmalonamic Acid (3a). A mixture of benzenesulfonylamide
(45.2 g, 0.3 mol), acid chloride of the monoethyl ester of malonic acid (47.2 g, 0.3 mol), and dry benzene
(60 ml) was heated at 65-70°C for 15-20 h until completely dissolved. The reaction mixture was then cooled and
564

filtered through a 1-cm layer of silica gel. The benzene solution was extracted with dilute aqueous ammonia.
The aqueous solution was brought to pH 2 and 3a was isolated as an oil, which gradually crystallized. The
1
), δ, ppm,
product was recrystallized from carbon tetrachloride to give 50.1 g 3a. H NMR spectrum (DMSO-d6
J (Hz): 12.18 (1H, br. s, SO2NH); 7.60-8.05 (5H, m, Ph); 4.04 (2H, q, J = 7.3, OCH2); 3.35 (1H, s, CH2); 1.11
(3H, t, J = 7.3, CH3). IR spectrum, , cm-1: 3435, 3117 (NH), 2990, 2895 (CH), 1734 (CO2Et), 1702
ν
(CONHSO2).
Monoethyl Ester of N-Tosylmalonamic Acid (3b) was obtained analogously to 3a. 1H NMR spectrum
), δ, ppm,
(DMSO-d6
J (Hz): 12.2 (1H, br. s, SO2NH); 7.85 (2H, d, ArH); 7.70 (2H, d, ArH); 4.04 (2H, q, J = 7.3,
OCH2); 3.35 (1H, s, CH2); 2.29 (3H, s, ArCH3); 1.11 (3H, t, J = 7.3, CH3). IR spectrum, , cm-1: 3430, 3120
ν
(NH), 2990, 2895 (CH), 1735 (CO2Et), 1700 (CONHSO2).
N-Phenylsulfonylmalonamic Acid (4a). A sample of 3a (17 g, 62.7 mmol) in a solution of KOH
(7.41 g, 132 mmol) in water (20 ml) was heated for 3 h at 80°C. The reaction mixture was cooled to room
temperature and acidified to pH 2 by adding 1 N hydrochloric acid. The precipitated oil, which crystallized upon
cooling, was filtered off, washed with a small amount of cold water, dried in the air, and crystallized from
chloroform to give 12.6 g 4a. IR spectrum, , cm-1: 3545 (OH), 3450, 3030 (NH), 2990, 2895, 2776 (CH), 1705
ν
(CONHSO2), 1700 (CO2H).
N-Tosylmalonamic Acid (4b) was obtained analogously to 4a.
N,N'-Ditosylmalonamide (5a) was obtained analogously to 3a by heating malonyl chloride (14.1 g,
0.1 mol) in benzene (60 ml) with tosylamide (34.2 g, 0.2 mol). Yield of 5a 28.7 g.
N-Aryl-N'-arylsulfonylmalonamides (5b,c). General Method. A sample of dicyclohexylcarbodiimide
(2.37 g, 11.5 mmol) was added in portions with stirring to a solution of acid 4a or 4b (0.01 mol) and
corresponding aniline (0.01 mol) in dry dioxane (15 ml). The mixture was stirred for 10-15 h. The
dicyclohexylurea precipitated was filtered off and washed with dioxane (2 ml). The solution obtained was
brought to pH 2-3 by adding 1 N hydrochloric acid and diluted with water (60 ml). The precipitated oil
gradually crystallized. The product was filtered off and reprecipitated from 10% aqueous ammonia by adding
1 N hydrochloric acid to pH 2-3. The product was recrystallized from aqueous dioxane.
Sodium 4-N-arylcarbimidoyl-1-arylsulfonyl-1,2,3-triazole-5-olate (6a-c). General Method. A
solution of sodium (0.23 g, 10 mmol) in absolute ethanol (5 ml) was added with stirring to a solution or
suspension of malonamide 5a-c (5 mmol) in absolute ethanol (20 ml) at room temperature and, then,
benzenesulfonylazide (1 g, 5.5 mmol) was added. The mixture was left at room temperature for 24 h. The
precipitate formed was filtered off, washed with ethanol (2 ml), and dried over phosphorus pentoxide in
vacuum.
Sodium N-Aryl-N'-sulfonyldiazomalonimidolates (7a-c). General Method. A sample of malonamide
5a-c (5 mmol) in absolute ethanol or CCl4 (20 ml) was heated at reflux for 4-8 h and then cooled. The
precipitate formed was filtered off and dried over phosphorus pentoxide in vacuum.
2-Hydrazono-N-aryl-N'-arylsulfonylmalonamides (9a-c). General Method.
A
sample of
diazomalonamide 1a-c (5 mmol) in DMSO (2 ml) was heated at 85°C for 4 h. The reaction mixture was cooled
and 10% aqueous hydrazine hydrate (30 ml) was added. The precipitate formed was filtered off, crystallized
from ethanol, and dried over phosphorus pentoxide in vacuum.
4-(N-Methyl-N-arylcarbamoyl)-2-methyl-1-arylsulfonyl-1,2,3-triazolidin-5-one (10a-c). General
Method. A sample of methyl iodide (1.0 ml, 16 mmol) was added to a suspension of triazolate 6a-c (5 mmol) in
dry acetonitrile (30 ml) and stirred for 3 h at room temperature. The precipitate was filtered off, crystallized
from ethanol, and dried over phosphorus pentoxide in vacuum.
This work was carried out with the financial support of the Russian Fund for Basic Research,
Grant 98-03-33045-a.
565

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