1-Hetaryltriazenes in the synthesis of condensed mesoionic 1,2,3-triazolio-5-olates

Article abstract of DOI:10.1007/s10593-006-0264-2

Condensed mesoionic 1,2,3-triazoles containing an aryl or hetaryl substituent at N₍₂₎ in the ring have been synthesized by intramolecular condensation.

Full text of DOI:10.1007/s10593-006-0264-2

Chemistry of Heterocyclic Compounds, Vol. 42, No. 11, 2006
1-HETARYLTRIAZENES IN THE SYNTHESIS
OF CONDENSED MESOIONIC 1,2,3-TRIAZOLIO-
5-OLATES
Yu. I. Nein, S. V. Gladkova, T. A. Pospelova, and Yu. Yu. Morzherin
Condensed mesoionic 1,2,3-triazoles containing an aryl or hetaryl substituent at N(2) in the ring have
been synthesized by intramolecular condensation.
Keywords: imidazole, mesoionic heterocycles, triazenes, 1,2,3-triazole, intramolecular condensation.
Several approaches are known for the synthesis of monocyclic mesoionic heterocycles [1, 2], while the
number of reported mesoionic condensed heterocycles is very limited [3-5]. Mesoionic 1,2,3-triazoles condensed
with a six-membered ring hold interest for to their biological properties [6-8]. One of the methods for the
synthesis of 1,2,3-triazolio-5-olates [9] involves the intramolecular cyclization of triazenes [10], although only
one example of a synthesis of a condensed mesoionic 1,2,3-triazole by this method has been reported [11].
H
N
CO2H
Ar
N
(
)
n
(
)
n
Ac2O
N
N+
5, 7
N
(
)
–
–
N
n
Cl
O
N
HO2C
Me
+
N2
2a–e
Ar
Ar
3a–c
1 a–e
O
Me
O
Me
Me
O
O
Ac2O
Py
Me
O
O
N+
N
N
N
OH
COOH
–
O
N
N
.
NH
HCl
O
Ar
1f,g
Ar
6
Me
2f,g
1,2 a,c,f,g Ar = Ph, b,d Ar = C6H4F-4, e Ar = C6H4COOEt-4; 3 a Ar = Ph, b Ar = C6H4F-4,
c Ar = C6H4COOEt-4; 1,2 a,b n = 1, c−e n = 2; 5 n = 1; 7 n = 2
_______
* Dedicated to Academician M. G. Voronkov on his Eighty-Fifth Birthday.
__________________________________________________________________________________________
Urals State Technical University---UPI, 62002 Ekaterinburg, Russia, e-mail: morzherin@htf.ustu.ru.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1714-1719, November, 2006. Original article
submitted August 7, 2006.
1472
0009-3122/06/4211-1414©2006 Springer Science+Business Media, Inc.

No such reactions have been reported for the synthesis of 1,2,3-triazoles containing heterocyclic
substituents at N(1). In the present work, we report the synthesis of condensed mesoionic [1,2,3]triazoles 1
starting from triazenes 2 generated from diazonium salts of aromatic 3 or heterocyclic diazo compounds 4 and
cyclic α-amino acids, namely, 2-aziridinecarboxylic acid, 2-azetidinecarboxylic acid, proline 5,
6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 6, and pipecolinic acid 7.
H
N
+
N
N
CO2H
–
N
CO2H
O
N
N
+
N
Ar
N2
Ar
Ar
8
3a–c
+
N
N
N
–
N
H
CO2H
O
N
N
N
Ar
Ar
CO2H
9
We have shown that mesoionic triazoles are formed only upon condensation to five- and six-membered
heterocycles. Mesoionic heterocycles 8 and 9 are not formed upon treating triazenes obtained from
1-aziridinecarboxylic and 2-azetidinecarboxylic acids with acetic anhydride. This failure is presumably related to
the instability of the resultant condensed rings 8 and 9 as a consequence of strain of the C–C bonds in the small
rings.
N
R
n
(
)
X
R
N
+
N
Ac2O
Py
5, 7
H
N
N
N
–
X
O
N
N2
N
N
N
R
4a,b
NH
(
)
HO2C
n
Me
N
X
6
2h–k
O
1h–k
O
Py
Ac2O
Me
R
R
R
N
N
N
N
N
N
X
N
X
N
N
HOOC
N
X
N
N
N
H
2l,m
HO
N
O
N
H
Ac2O
Py
Me
(
)
(
)
n
n
O
10
+
N
O
Me
N
R
N
N
–
NH
O
X
1l,m
1, 2 h,j,l R = CO2Et, X = CH; i,k,m R = CONHC6H11-cyclo, X = N; h,i n = 1, j–m n = 2
1473

Intramolecular condensation to give 1,2,3,4-tetrazepins 10 is possible in the case of triazenes 2h-m
containing 1H-1,2,3-triazole (4a) or 1H-imidazole (4b) at N(3). However, we have shown that these compounds
yield the more stable mesoionic 1,2,3-triazoles 1h-m. Thus, for example, the azo coupling reaction of
5-diazoimidazole 4b with proline 5 gives triazine 2b, isolated as two positional isomers relative to the N=N
bond. Intramolecular condensation in acetic anhydride leads to pyrrolo[1,2-c][1,2,3]triazolio-5-olate 1h.
1
The H NMR spectra of 1h-m lack a methine proton signal, which should have been observed in the
spectrum of 10, but the signal for the acid proton at 11-13 ppm can be assigned both to the NH group proton and
OH proton of the enolic form of 10. In this case, the signal for the carbonyl (or enolic) carbon should be seen as
13
a doublet split by the imidazole proton with J = 3-5 Hz in the C NMR spectrum of products 10 obtained from
diazoimidazole 4b. However, the signal for the carbon atom attached to N(3) in the ring is seen as a singlet at
156 ppm. The mass spectrum of 1h shows a molecular ion peak [M]+ 263* (I = 57%) corresponding to the
chemical formula. Elimination of a nitrogen molecule is characteristic for heterocycles containing an N=N
fragment and the corresponding fragment ion peak has high intensity [12]. The molecular ion M+ in the spectrum
of 1h, having eliminated a nitrogen molecule, decomposes to give fragment Φ3 235 (2.2%), which then may
decompose to give fragments Φ6 96 (28%) and Φ7 139 (19%). Also, the resultant fragment ion Φ1 191 (I = 23%)
eliminates –CH2–CH2–CH2–CH–C–O- to give fragment Φ4 111 (86%) and Φ5 105 (4%). The third pathway for
decomposition of the molecular ion proceeds initially to give fragment species Φ2 167 (100%) and then with the
loss of molecular nitrogen. The subsequent decomposition of fragment ions Φ4, Φ5, and Φ7 proceeds to give
imidazole Φ8 68 (84%).
NH
+
+
N
O
H
N
N
Ф9
N
–CO2Et
+ H+
N
N
m/z 83 (38%)
O
O
N
N
+2H+
HC
NH
EtO2C
N
C
NH
NH
H
Ф4
N
N
m/z 111 (86%)
+
[M]
Ф1
m/z 263 (57%)
m/z 191 (23%)
–N2
Ф6
m/z 96 (28%)
Ф9
m/z 83 (38%)
N
N
NH
O
N
N
NH
EtO2C
Ф8
NH
m/z 68 (84%)
N
N
N
Ф3
NH
m/z 235 (2.2%)
N
EtO2C
NH
Ф5
m/z 108 (4%)
N
Ф2
m/z 167 (100%)
+2H+
NH
EtO2C
N
–CO2Et
O
N
Ф7
m/z 139 (19%)
Ф6
m/z 96 (28%)
_______
*
Here and subsequently, the m/z (Irel, %) values are given for the mass spectra.
1474

Thus, we have shown that a broad range of mesoionic 1,2,3-triazole derivatives may be obtained by the
intramolecular condensation of triazenes.
EXPERIMENTAL
The reaction course and purity of the products were checked by thin-layer chromatography on
Silufol UV-254 plates using 1:10 and 1:5 ethyl acetate–hexane as eluents. The NMR spectra were taken on a
1
Bruker WM-250 spectrometer at 250 MHz for the H NMR spectra and a Bruker DRX-400 spectrometer at
1
400 MHz for the H NMR spectra and 100 MHz for the 13C NMR spectra for solutions in DMSO-d6 (the
13C NMR spectrum of 1l) and DMSO-d6–CCl4 for the other compounds. TMS served as the internal standard.
The mass spectra were taken on a Varian MAT-311A mass spectrometer with 70 eV ionizing voltage and direct
sample inlet into the ion source.
Preparation of zwitter-ionic triazoles 1 from triazenes 2 (general method). A solution of 0.186 g
(2.7 mmol) sodium nitrite in a minimal volume of water was added dropwise to a stirred solution of 1.1 mmole
aromatic amine in 0.54 ml (2.7 mmol) 5 N hydrochloric acid at 0-5°C. The reaction endpoint was monitored
using iodine–starch paper. The yellow diazo compound solution obtained was added dropwise to a solution of
1.1 mmol N-substituted α-amino acid in 1 N aq. NaOH cooled to 0-5°C. The solution turned dark red.
Concentrated hydrochloric acid was added to bring the solution to pH 4 and the precipitate formed was filtered
off. The triazene obtained was dissolved in 5 ml pyridine and 5 ml acetic anhydride. The reaction mixture turned
a dark black–brown and was left stand for 15 h at room temperature. The solvent was evaporated off in vacuum.
The residue was dissolved in water and extracted with three 15-ml chloroform portions. The organic extract was
evaporated in vacuum. Hexane was added to a minimal volume of chloroform to give a precipitate, which was
filtered off and washed with hexane.
1-Phenyl-2,4,5,6-tetrahydropyrrolo[1,2-c][1,2,3]triazolio-5-olate (1a) was obtained in 69% yield
(0.152 g), mp 107°C. 1H NMR spectrum, δ, ppm (J, Hz): 7.98 (2H, d, J = 8.7, ArH), 7.43 (2H, dd, J = 7.5, ArH),
7.28 (1H, t, J = 7.5, ArH), 4.35 (2H, t, J = 7.4, CH2), 2.87 (2H, t, J = 7.6, CH2), 2.63 (2H, tt, J = 7.4, J = 7.6,
CH2). Mass spectrum, m/z (Irel, %): 201 (48). Found, %: N 20.53. C11H11N3O. Calculated, %: N 20.89.
2-(4-Fluorophenyl-2,4,5,6-tetrahydropyrrolo[1,2-c][1,2,3]triazolio-5-olate (1b) was obtained in 68%
yield (0.16 g), mp 57°C. 1H NMR spectrum, δ, ppm (J, Hz): 8.00 (2H, dd, J = 12.1, J = 6.4, ArH), 7.20 (2H, dd,
J = 9.3, J = 8.7, ArH), 4.36 (2H, t, J = 7.3, CH2), 2.87 (2H, t, J = 6.4, CH2), 2.64 (2H, tt, J = 7.3, J = 6.4, CH2).
13C NMR spectrum, δ, ppm: 161.43 (dt, 1JF = 243.8, J = 6.0, C-p), 153.81 (s, C(3)), 134.27 (dt, 4JF = 2.7, J = 7.9,
3
C-i), 123.20 (ddd, JF = 8.4, J = 173.6, J = 7.4, C-o), 122.67 (ttt, J = 5.5, J = 5.2, J = 3.4, C (3a)), 116.87 (ddd,
2JF = 8.4, J = 170.5, J = 8.9, C-m), 50.91 (ttt, J = 148.6, J = 2.6, J = 2.7, C(6)), 25.90 (ttt, J = 135.5, J = 3.1,
J = 2.7, C(4)), 22.73 (ttt, J = 136.1, J = 3.4, J = 2.3, C(5)). Mass spectrum, m/z (Irel, %): 219 (87). Found, %:
N 18.60. C11H10FN3O. Calculated, %: N 19.17.
2-Phenyl-4,5,6,7-tetrahydro-2H-[1,2,3]triazolo[1,5-a]pyridinio-3-olate (1c) was obtained in 47%
yield (0.117 g), mp 118°C. 1H NMR spectrum, δ, ppm (J, Hz): 8.00 (2H, dd, J = 8.7, J = 1.2, ArH), 7.51 (2H, dd,
J = 8.1, J = 7.6, ArH), 7.36 (1H, t, J = 7.4, ArH), 4.25 (2H, t, J = 6.0, CH2), 2.55 (2H, t, J = 6.3, CH2), 2.03-1.96
(2H, m, CH ), 1.86-1.81 (2H, m, CH2). Mass spectrum, m/z (Irel, %): 215 (70). Found, %: N 19.33. C12H13N3O.
2
Calculated, %: N 19.52.
2-(4-Fluorophenyl)-4,5,6,7-tetrahydro-2H-[1,2,3]triazolo[1,5-a]pyridinio-3-olate (1d) was obtained
1
in 71% yield (0.182 g), mp 135°C. H NMR spectrum, δ, ppm (J, Hz): 8.10-8.00 (2H, m, ArH), 7.30-7.12 (2H,
m, ArH), 4.22 (2H, t, J = 6.1, CH2), 2.61 (2H, t, J = 6.1, CH2), 2.15-1.99 (2H, m, CH2), 1.98-1.83 (2H, m, CH2).
Mass spectrum, m/z (Irel, %): 233 (74). Found, %: N 18.32. C12H12FN3O. Calculated, %: N 18.02.
1-(4-Ethoxycarbonylphenyl)-4,5,6,7-tetrahydro-2H-[1,2,3]triazolo[1,5-a]pyridinio-3-olate (1e) was
1
obtained in 55% yield (0.174 g), mp 135°C. H NMR spectrum, δ, ppm (J, Hz): 8.22 (2H, d, J = 8.8, ArH),
1475

8.05 (2H, d, J = 8.9, ArH), 4.33 (2H, q, J = 7.2, OCH2), 4.25 (2H, t, J = 6.4, CH2), 2.62 (2H, J = 6.4, CH2),
2.22-2.02 (2H, m, CH2), 2.00-1.82 (2H, m, CH2), 1.39 (3H, t, J = 7.2, CH3). Mass spectrum, m/z (Irel, %):
287 (39). Found, %: N 14.26. C15H17N3O3. Calculated, %: N 14.62.
7,8-Dimethoxy-2-phenyl-5,10-dihydro-2H-[1,2,3]triazolo[1,5-b]isoquinolinio-3-olate
(1f)
was
obtained in 62% yield (0.220 g), mp 107°C. 1H NMR spectrum, δ, ppm (J, Hz): 8.03 (2H, d, J = 7.6, C6H5), 7.51
(1H, s, ArH), 7.50 (2H, dd, J = 7.7, J = 7.6, C6H5), 7.41 (1H, s, ArH), 7.38 (1H, t, J = 7.6, C6H5), 6.94 (2H, s,
CH2), 5.43 (2H, s, CH2), 3.92 (3H, s, OCH3), 3.81 (3H, s, OCH3). Mass spectrum, m/z (Irel, %). Found, %:
N 12.81. C18H17N3O3. Calculated, %: N, 13.00.
2-(4-Fluorophenyl)-7,8-dimethoxy-5,10-dihydro-2H-[1,2,3]triazolo[1,5-b]isoquinolinio-3-olate (1f)
1
was obtained in 73% yield (0.274 g), mp 242°C. H NMR spectrum, δ, ppm (J, Hz): 8.13-8.06 (2H, m, ArH),
7.30-7.21 (2H, m, ArH), 6.96 (1H, s, ArH), 6.94 (1H, s, ArH), 5.39 (2H, s, CH2), 3.88 (2H, s, CH2), 3.81 (3H, s,
OCH ), 3.80 (3H, s, OCH3). Mass spectrum, m/z (Irel, %): 341 (95). Found, %: N 12.46. C18H16FN3O3.
3
Calculated, %: N 12.32.
2-(4-Ethoxycarbonyl-1H-imidazol-5-yl)-2,4,5,6-tetrahydropyrrolo[1,2-c][1,2,3]triazolio-3-olate (1h)
1
was obtained in 78% yield (0.225 g), mp 132°C. H NMR spectrum, δ, ppm (J, Hz): 13.5 (1H, br. s, NH), 7.95
(1H, s, CH), 4.37 (2H, t, J = 7.5, CH2), 4.15 (2H, q, J = 7.1, OCH2), 2.78 (2H, t, J = 7.2, CH2), 2.59 (2H, tt,
J = 7.5, J = 7.2, CH2), 1.15 (3H, t, J = 7.1, CH3). Mass spectrum, m/z (Irel, %): 263 (57). Found, %: N 26.80.
C11H13N5O3. Calculated, %: N 26.60.
2-(4-Cyclohexylaminocarbonyl-1H-1,2,3-triazol-5-yl)-2,4,5,6-tetrahydropyrrolo[1,2-c][1,2,3]-
triazolio-3-olate (1i) was obtained in 27% yield (0.094 g), mp, 71°C. 1H NMR spectrum, δ, ppm (J, Hz): 8.54
(1H, d, J = 5.6, CONH), 7.39 (1H, br. s, NH), 4.96 (2H, t, J = 6.2, CH2), 2.98-2.88 (1H, m, CH), 2.85-2.74 (2H,
m, CH2), 2.00-1.92 (8H, m, CH2), 1.61-1.22 (4H, m, CH2). Mass spectrum, m/z (Irel, %): 317 (60). Found, %:
N 30.73. C14H19N7O2. Calculated, %: N 30.90.
2-(4-Ethoxycarbonylimidazol-1-yl)-4,5,6-tetrahydro-2H-[1,2,3]triazolo[1,5-a]pyridinio-3-olate (1j)
was obtained in 62% yield (0.189 g). 1H NMR spectrum, δ, ppm (J, Hz): 13.6 (1H, br. s, NH), 7.76 (1H, s, CH),
4.59 (2H, t, J = 6.2, CH2), 4.22 (2H, t, J = 7.2, OCH2), 2.79 (2H, t, J = 7.2, CH2), 2.15-1.86 (4H, m, CH2), 1.18
13
(3H, t, J = 7.2, CH3). C NMR spectrum, δ, ppm (J, Hz): 172.05 (q, J = 6.6, CO2), 159.19 (br. s, Cim-4), 156.07
(t, J = 1.5, C(3)), 149.19 (br. s, C(7)), 148.62 (br. s, C(6)), 138.13 (d, J = 213.0, CHim-2), 122.83 (br. s, C(8)), 110.66
(br. s, s, Cim-5), 118.91 (br. s, C(4a)), 113.00 (d, J = 162.0, C(5)), 112.53 (d, J = 170.8, C(8), 110.66 (br. s, C(3a)),
61.04 (tq, J = 148.5, J = 4.3, OCH2), 56.60 (q, J = 144.4, OCH3), 56.61 (q, J = 144.4, OCH3), 50.72 (td, J =
143.5, J = 5.5, C(9), 25.00 (td, J = 133.2, J = 0.8, C(4)), 14.64 (qt, J = 127.1, J = 2.7, CH3). Mass spectrum, m/z
(Irel, %): 277 (60). Found, %: N 25.13. C12H15N5O3. Calculated, %: N 25.27.
2-(4-Cyclohexylaminocarbonyl-1H-1,2,3-triazol-5-yl)-4,5,6,7-tetrahydro-2H-[1,2,3]triazolo[1,5-a]-
1
pyridinio-3-olate (1k) was obtained in 27% yield (0.098 g), mp 82°C. H NMR spectrum, δ, ppm (J, Hz): 8.54
(1H, d, J = 5.6, CONH), 7.38 (1H, br. s, NH), 4.96 (2H, t, J = 6.2, CH2), 2.98-2.70 (3H, m, CH+CH2), 2.10-1.74
(10H, m, CH2), 1.61-1.22 (4H, m, CH2). Mass spectrum, m/z (Irel, %): 331 (55). Found, %: N 29.22.
C15H21N7O2. Calculated, %: N 29.59.
2-(4-Ethoxycarbonyl-1H-imidazol-5-yl)-7,8-dimethoxy-5,10-dihydro-2H-[1,2,3]triazolo[1,5-b]-
1
isoquinolinio-3-olate (1l) was obtained in 59% yield (0.250 g), mp 163°C. H NMR spectrum, δ, ppm (J, Hz):
12.2 (1H, br. s, NH), 7.74 (1H, s, CHim), 6.95 (1H, s, ArH), 6.94 (1H, s, ArH), 5.38 (2H, s, CH2N), 4.15 (2H, q,
J = OCH2), 1.12 (3H, t, J = 7.2, CH3). 13C NMR spectrum, δ, ppm (J, Hz): 159.19 (br. s, C(3)), 156.07
(t, J = 1.5, CO2), 149.19 (br. s, C(7)), 148.62 (br. s, C(6)), 138.13 (d, J = 213.0, CHim-2), 122.83 (br. s, C(8a)),
121.27 (br. s, Cim-4), 118.91 (br. s, C(4a)), 113.00 (d, J = 162.0, C(5)), 112.53 (d, J = 170.8, C(8)), 111.42 (br. s,
C
im-5), 110.66 (br. s, C(3a)), 61.04 (tq, J = 148.5, J = 4.3, OCH2), 56.60 (q, J = 144.4, OCH3), 56.61 (q, J = 144.4,
OCH3), 50.72 (td, J = 143.5, J = 5.5, C(9)), 25.00 (td, J = 133.2, J = 0.8, C(4)), 14.64 (qt, J = 127.1, J = 2.7, CH3).
Mass spectrum, m/z (Irel, %): 384 [M - 1] (25). Found, %: N 18.06. C18H19N5O5. Calculated, %: N 18.17.
1476

2-(4-Cyclohexylaminocarbonyl-1H-1,2,3-triazol-7,8-dimethoxy-5-yl)-5,10-dihydro-2H-[1,2,3]-
1
triazolo[1,5-b]isoquinolinio-3-olate (1m) was obtained in 73% yield (0.352 g), mp 137°C. H NMR spectrum,
δ, ppm (J, Hz): 11.21 (1H, br. s, NH), 8.90 (1H, d, J = 5.6, CONH), 7.31 (1H, s, ArH), 6.99 (1H, s, ArH), 5.40
(2H, s, CH2), 4.30 (2H, s, CH2), 3.94 (3H, s, OCH3), 3.81 (3H, s, OCH3), 3.90-3.02 (1H, m, CH), 2.05-1.54 (8H,
m, CH2), 1.50-1.04 (2H, m, CH2). Mass spectrum, m/z (Irel, %): 439 (28). Found, %: N 22.11. C21H25N7O4.
Calculated, %: N 22.31.
This work was carried out with the financial support of the Russian Basic Research Fund
(04-03-96104-p, 04-03-96116-p).
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1477