Synthesis of 1-aryl(hetaryl)-1,2,3-triazoles with the use of ionic liquids

Article abstract of DOI:10.1070/MC2002v012n03ABEH001590

1-Phenyl(furazanyl)-1,2,3-triazoles can be synthesised by the 1,3-dipolar cycloaddition of phenylazide 1 or 4-amino-3-azido-furazan 2 to acetylenes (or to 1-morpholinyl-2-nitroethene for 2) in ionic liquids { 1-butyl-3-methylimidazolium tetrafluoroborate

Full text of DOI:10.1070/MC2002v012n03ABEH001590

Mendeleev Commun., 2002, 12(3), 83–84
Synthesis of 1-aryl(hetaryl)-1,2,3-triazoles with the use of ionic liquids
Ilya V. Seregin, Lyudmila V. Batog and Nina N. Makhova*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 135 5328; e-mail: mnn@mail.ioc.ac.ru
1
0.1070/MC2002v012n03ABEH001590
1
-Phenyl(furazanyl)-1,2,3-triazoles can be synthesised by the 1,3-dipolar cycloaddition of phenylazide 1 or 4-amino-3-azido-
furazan 2 to acetylenes (or to 1-morpholinyl-2-nitroethene for 2) in ionic liquids {1-butyl-3-methylimidazolium tetrafluoroborate
(
[bmim][BF ]) for 1 or 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF ]) for 2}.
4
6
Ionic liquids are promising reaction media for organic syn-
thesis, which can be repeatedly used for performing reactions
HOH C
CH OH
2
2
1
i
in place of ordinary organic solvents. Ionic liquids were used in
PhN3
+
HOCH C CCH OH
2 2
2
3
N
N
the Friedel–Crafts reaction, the dimerisation of alkenes, the
Ph
4
5,6
1
5a
alkylation of carbonyl compounds, the Heck reaction, and
the Diels–Alder reaction. As a rule, these reactions were con-
N
7
4
siderably accelerated in ionic liquids; therefore, the reactions
can be carried out under milder conditions. The regioselectivity
Scheme 2 Reagents and conditions: i, [bmim][BF4], 3 h, 120 °C.
8
increases in the case of ambident substrates. In this context,
the synthesis of heterocyclic compounds in ionic liquids seems
to be promising. Only several works concerning this problem
were published, in particular, the synthesis of oxazoline or imi-
dazoline derivatives by the 1,3-dipolar cycloaddition of imidates,
which were prepared from diethylaminomalonate, to 2-ethoxy-
ever, the test reaction does almost not occur at this temperature.
An increase in the temperature results in the partial decomposi-
tion of the ionic liquid.
Thus, using this model example, we found that ionic liquids
that are stable in air at room temperature can serve as a reaction
medium for the preparation of 1-substituted 1,2,3-triazoles by
the 1,3-dipolar cycloaddition of azides to acetylene derivatives.
This reaction occurred at a much higher rate than in standard
organic solvents. Thus, we believed that the ionic liquids can
also be successfully used for the synthesis of compounds 3.
To evaluate the effect of ionic liquids, we examined the
reaction between 3-azido-4-aminofurazan 2 and dipolarophiles
(butynediol 5a, propargyl alcohol 5b, and 1-morpholinyl-2-
nitroethylene 5c), which were previously entered into the reac-
tion with azide 2, at 75–80 °C (Scheme 3). We found that under
these conditions the reaction was considerably accelerated only
9
(a),(b)
benzaldehyde or imines as dipolarophiles,
the preparation
of indoles9 and the synthesis of 3,4-dihydropyrimidine-
(c)
(1H)-one.9
(d)
2
Recently, 3-(4-nitro-1,2,3-triazol-1-yl)-4-R-furazans and 3-[4(5)-
alkyl- or 4,5-dialkyl-1,2,3-triazol-1-yl]-4-R-furazans 3 were syn-
thesised in our laboratory by the 1,3-dipolar cycloaddition of
1
0
azidofurazanes to 1-morpholinyl-2-nitroethylene and substituted
acetylenes,11 respectively, in standard solvents. In a number of
cases, the reaction with monosubstituted acetylenes occurred
regioselectively. These bicyclic compounds potentiate the NO-
dependent activation of soluble guanylate cyclase; that is, they
1
2
are nitrogen oxide donors. However, compounds 3 can be
synthesised under severe conditions (120 h at 110 °C for 1-mor-
pholinyl-2-nitroethylene and 20–120 h at 65–80 °C for acetylene
derivatives). We performed the above reactions in ionic liquids
in order to develop a more efficient synthetic procedure for
triazolylfurazans 3.
in [bmim][PF ]. Table 1 summarises the reaction conditions.
6
R1
R2
R1
N
R2
5a,b
H N
2
N3
H N
2
N
N
N
At the first stage, we synthesised 4,5-bis(hydroxymethyl)-
N
O
N
CH CH NO2
O
N
N
1
-phenyl-1,2,3-triazole 4 by the 1,3-dipolar cycloaddition of
5c
1
3
phenylazide 1 to butynediol 5a. According to published data,
2
O
this reaction can be performed only at 120 °C for 12 h. The
following ionic liquids based on 1-methylimidazole were chosen:
butylmethylimidazolium hexafluorophosphate [bmim][PF6]1
and butylmethylimidazolium tetrafluoroborate [bmim][BF4]15
3a–d
1
2
1
2
4
a R = R = CH2OH
c R = H, R = CH2OH
1
2
1
2
b R = CH OH, R = H
d R = H, R = NO
2
2
(
Scheme 1). These ionic liquids are readily available and stable
Scheme 3
to air and moisture.
Data given in Table 1 indicate that azide 2 more rapidly
reacted with acetylene derivatives 5a,b than in the case when
published procedures were used. The yields of 4-amino-3-[4,5-
bis(hydroxymethyl)-1,2,3-triazol-1-yl]furazan 3a and a mixture
of 4-amino-3-(5-hydroxymethyl-1,2,3-triazol-1-yl)furazan 3b
i
Cl
N
N
N
N
Me
Bu
Me
ii or iii
X
† All compounds were previously described; thus, they were characterised
by a comparison of their melting points and spectroscopic data with
N
N
Bu
Me
1
published data. H NMR spectra were measured on Bruker WM-250
Scheme 1 Reagents and conditions: i, BuCl, toluene, reflux, 24 h; ii, (for
X = PF ), HPF , H O, 20 °C, 12 h; iii, (for X = BF ), NH BF , acetone,
(
250 MHz) and Bruker AM-300 (300 MHz) spectrometers. TLC moni-
6
6
2
4
4
4
2
0 °C, 24 h.
toring was performed on Silufol UV 254 silica gel plates, the eluent was
chloroform–acetone–methanol (10:2:1) or benzene–acetone (9:1). Melting
points were determined on a Boetius PHMK 05 instrument.
The interaction of phenylazide 1 with butynediol 5a was
studied in both of the ionic liquids at 80–120 °C. The use of
bmim][BF ] at 120 °C for 3 h was found to be optimum; the
4
,5-Bis(hydroxymethyl)-1-phenyl-1,2,3-triazole 4. A mixture of 0.85 mmol
of phenylazide 1, 0.80 mmol of a substituted acetylene and 1.5 mmol of
bmim]BF4 was stirred at 120 °C for 3 h. The reaction mixture was
[
4
[
yield of compound 4 was comparable to the yield obtained in
cooled to room temperature and extracted with ethyl acetate (3×10 ml).
The solvent was evaporated, the residue was treated with a minimum
volume of acetone, the precipitate was filtered off, washed with 10 ml of
acetone and dried in air.
†
accordance with the known procedure (Scheme 2; Table 1,
entry 1).13 We found that the [bmim][PF ] ionic liquid can be
6
used in this reaction at temperatures no higher than 90 °C; how-
–
83 –

Mendeleev Commun., 2002, 12(3), 83–84
References
Table 1 Reagents, conditions and results of the synthesis of 1,2,3-tri-
azoles in ionic liquids.
1
2
T. Welton, Chem. Rev., 1999, 99, 2071.
J. A. Boon, J. A. Levitsky, J. L. Pflug and J. S. Wilkes, J. Org. Chem.,
986, 51, 480.
1
,2,3-
Conditions and
yields according
to published data
1
Dipolaro- Ionic liquids
Entry Azide
triazoles
phile
and conditions
3
S. M. P. Silva, A. Z. S. Suarez, R. F. De Souza and J. Dupont, Polym.
Bull., 1998, 40, 401.
(
yields)
1
2
3
1
2
2
5a
[bmim]BF4,
4 (65%)
Benzene, 120 °C,
12 h (73%)
4
5
C. M. Gordon and A. McCluskey, Chem. Commun., 1999, 337.
A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B. McCormac and K. R.
Seddon, Org. Lett., 1999, 1, 997.
V. P. W. Bohm and W. A. Hermann, Chem. Eur. J., 2000, 6, 1017.
T. Fischer, A. Shethi, T. Welton and J. Woolf, Tetrahedron Lett., 1999,
40, 793.
M. J. Earle, P. B. McCormac and K. R. Seddon, Chem. Commun., 1998,
2245.
(a) J. Fraga-Dubreuil and J. P. Bazureau, Tetrahedron Lett., 2000, 41,
1
3
1
20 °C, 3 h
[bmim]PF6,
0 °C, 7.5 h
[bmim]PF6,
0 °C, 6.5 h
5a
5b
3a (75%) EtOH, reflux, 30 h
8
(57%)11
6
7
3b:3c, 4.5:1 EtOH, reflux,
8
(71%)
45 h, 3b:3c, 2.5:1
79%)11
3d (35%) Toluene, reflux,
(
8
9
4
2
5c
[bmim]PF6,
0 °C, 12 h
1
0
7
120 h (80%)
7351; (b) J. Fraga-Dubreuil and J. P. Bazureau, Tetrahedron Lett., 2001,
4
2, 6097; (c) G. L. Rebeiro and B. M. Khadikar, Synthesis, 2001, 370;
and 4-amino-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)furazan 3c
‡
(d) J. Peng and Y. Deng, Tetrahedron Lett., 2001, 42, 5917.
(
entries 2,3) were comparable or even higher. In the reaction
1
0 L. V. Batog, V. Yu. Rozhkov, Yu. A. Strelenko, O. V. Lebedev and L. I.
Khmel’nitskii, Khim. Geterotsikl. Soedin., 2000, 100 [Chem. Heterocycl.
Compd. (Engl. Transl.), 2000, 36, 91].
11 L. V. Batog, L. S. Konstantinova, V. Yu. Rozhkov, Yu. A. Strelenko,
O. V. Lebedev and L. I. Khmel’nitskii, Khim. Geterotsikl. Soedin.,
2000, 406 [Chem. Heterocycl. Compd. (Engl. Transl.), 2000, 36, 343].
12 L. V. Batog, V. Yu. Rozhkov, Yu. V. Khropov, N. V. Pyatakova, O. G.
Bousygina, I. S. Severina and N. N. Makhova, Russ. Pat. 2158265,
with propargyl alcohol 5b, the 3b:3c ratio between isomers
noticeably changed in favour of compound 3b; that is the use
of the [bmim][PF ] ionic liquid as a reaction medium for the
6
interaction of azidofurazan 2 with monosubstituted acetylene
increased the regioselectivity of the reaction.
The reaction with compound 5c was completed in 12 h at
0 rather than 110 °C. However, in this case, the yield of
-amino-3-(4-nitro-1,2,3-triazol-1-yl)furazan 3d was lower than
§
7
4
2
000.
1
1
1
3 W. Winter and E. Muller, Chem. Ber., 1974, 107, 715.
4 D. W. Armstrong, L. He and Y.-S. Liu, Anal. Chem., 1999, 71, 3873.
5 P. A. Suarez, J. E. L. Dullius, S. Einloft, R. F. de Souza and J. Dupont,
Polyhedron, 1996, 15, 1217.
the published value. Evidently, morpholine, which was released
in the course of reaction, reacted with the final product to
decrease its yield. It is likely that the rate of this reaction in the
ionic liquid also increased. The accumulation of by-products in
the course of reaction was detected by TLC monitoring.
The possibility of repeatedly using an ionic liquid was tested
by the example of the synthesis of compound 3a, which was
performed three times in the same portion of an ionic liquid
with almost no decrease in the yield.
Thus, we found that ionic liquids can be successfully used as
reaction media for the synthesis of 1-aryl(hetaryl)-1,2,3-triazoles
by the 1,3-dipolar cycloaddition of both aromatic and hetero-
cyclic azides to substituted acetylenes and enamines. Both the
rate and the regioselectivity of the reaction increased as com-
pared to analogous reactions in standard organic solvents. These
results form the basis for a promising new branch of the
chemistry of heterocyclic compounds – the use of ionic liquids
for performing heterocyclisation reactions.
This study was supported by a complex scientific programme
of the Russian Academy of Sciences (2001–2002).
‡
2
1
4
-Amino-3-(4-R -5-R -1,2,3-triazol-1-yl)furazans 3a–c (general pro-
cedure). A mixture of 1 mmol of 4-amino-3-azidofurazan 2, 1.25 mmol
of a substituted acetylene and 2 mmol of [bmim]PF6 was stirred at
7
5–80 °C for 3.5 to 7.5 h. The reaction mixture was cooled to room
temperature and treated with a minimum volume of acetone, the pre-
cipitate was filtered off and washed with 10 ml of acetone. The solvent
was evaporated and the residue was treated with 10 ml of acetone, the new
precipitate was filtered off and washed with 5 ml of acetone. The last
operation was repeated once more. Combined portions of the precipitate
were dried in air. The ionic liquid can be easily recovered and reused
after the evaporation of acetone. The ratio between compounds 3b and
3
c in the mixture was calculated from 1H NMR-spectroscopic data
according to the integral intensities of corresponding proton signals in
2
[
H ]DMSO: 3b, 4.67 (d, 2H, 5'-CH ), 5.44 (t, 1H, OH), 8.65 (s, 1H,
6
2
4
'-CH); 3c, 4.80 (d, 2H, 4'-CH ), 5.69 (t, 1H, OH), 7.96 (s, 1H, 5'-CH).
2
§
4
-Amino-3-(4-nitro-1,2,3-triazol-1-yl)furazan 3d. A mixture of 8 mmol
of 4-amino-3-azidofurazan 2 and 7 mmol of 1-morpholinyl-2-nitroethene
was added to 8 mmol of [bmim]PF and stirred at 70 °C for 12 h. The
6
reaction mixture was cooled to room temperature and extracted with
diethyl ether (3×20 ml). The solvent was evaporated under reduced pres-
sure and the product was isolated by column liquid chromatography. The
isolation of triazole 3d was performed by column liquid chromatography
using SiO (40:100) as a stationary phase and a mixture of benzene and
2
ethyl acetate (13:5) as an eluent.
Received: 10th April 2002; Com. 02/1916
–
84 –