Highly efficient synthesis of 4-trialkylsilyl(germyl)-1H-1,2,3-triazole-5- carbaldehydes

Full text of DOI:10.1134/S1070428012120196

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 12, pp. 1582–1584. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © M.M. Demina, T.L.H. Nguyen, N.S. Shaglaeva, A.V. Mareev, A.S. Medvedeva, 2012, published in Zhurnal Organicheskoi Khimii,
2012, Vol. 48, No. 12, pp. 1611–1613.
SHORT
COMMUNICATIONS
Highly Efficient Synthesis
of 4-Trialkylsilyl(germyl)-1H-1,2,3-triazole-5-carbaldehydes
M. M. Deminaa, T. L. H. Nguyenb, N. S. Shaglaevab, A. V. Mareeva, and A. S. Medvedevaa
a Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: amedved@irioch.irk.ru
b National Research Irkutsk State Technical University, ul. Lermontova 83, Irkutsk, 664074 Russia
Received August 29, 2012
DOI: 10.1134/S1070428012120196
A combination of such important properties of the
triazole ring as chemical stability, large dipole mo-
ment, heteroaromatic character, and the ability to form
hydrogen bonds via donor–acceptor interactions were
efficiently utilized in organic synthesis in the design of
biologically active molecules and new materials [1].
Although 1,2,3-triazole ring is lacking in natural com-
pounds, synthetic and biochemical studies on 1,2,3-tri-
azole derivatives have gained a new impetus in recent
years due to their use as bioisosters of amide group
in the design of new effective and safe drugs [2].
1,2,3-triazole-5-carbaldehydes in high yield via regio-
selective cycloaddition of trimethylsilyl azide to
3-heteroelement-substituted propynals on heating in
boiling toluene over a period of 24–36 h [7, 9].
With a view to optimize the procedure for the syn-
thesis of heteroelement-substituted triazolecarbalde-
hydes we studied the cycloaddition of trimethylsilyl
and benzyl azides to propynals Ia and Ib in aqueous
medium and demonstrated for the first time high
efficiency of water as solvent in the preparation of
triazoles from heteroelement-substituted alkynes. The
reactions of trialkylsilyl- and trialkylgermylpropynals
Ia and Ib with trimethylsilyl- and benzyl azides IIa
and IIb in water at room temperature (reaction time
18 h) gave triazoles IIIa–IIId in 85–98% yield. Ex-
perimental simplicity of the procedure should be noted.
There is no necessity of using chromatographic
methods for purification of the target products which
can be readily isolated from the reaction mixture.
Several synthetic approaches to 1,2,3-triazoles are
known [3], but the most practical and efficient proce-
dure for the synthesis of 1,4-disubstituted 1,2,3-tri-
azoles is now that based on the “click chemistry”
copper(I)-catalyzed reaction of azides with terminal
alkynes [4]. However, this procedure is inapplicable to
internal alkynes, and it does not ensure preparation of
triazoles having no substituent on the nitrogen.
R31M
CHO
Functionally substituted trialkylsilylalkynes are
promising as dipolarophiles in target-oriented syn-
theses of various 1,2,3-triazole derivatives due to high
regioselectivity of their cycloaddition to azides, which
produces 5-functionalized 4-trialkylsilyl-1H-1,2,3-tri-
azoles, both substituted and unsubstituted at the nitro-
gen atom [5]. Regioselective addition of azides to
the triple bond of trialkylgermylpropynals was re-
ported in [6, 7].
H2O, 25°C
18 h
R31M
CHO
+
R2N3
N
N
R3
N
Ia, Ib
IIa, IIb
IIIa–IIId
I, R13M = Me3Si (a), Et3Ge (b); II, R2 = Me3Si (a), Bzl (b);
II, R13M = Me3Si, R3 = H (a), Bzl (c); R31M = Et3Ge, R3 =
H (b), Bzl (d).
Increased interest in water as solvent for carrying
out organic reactions over the last decade is deter-
mined by the possibility for enhancing the reaction rate
and sometimes selectivity as compared to reactions in
common organic solvents, by the efficiency and en-
Traditional thermal 1,3-dipolar cycloaddition of
organic azides to alkynes (Huisgen reaction) requires
fairly severe conditions and is not selective [8]. We
previously synthesized 4-trialkylsilyl(germyl)-1H-
1582

HIGHLY EFFICIENT SYNTHESIS OF 4-TRIALKYLSILYL(GERMYL)-1H-1,2,3-TRIAZOLE-...
1583
vironmental safety of reactions in aqueous medium,
and by the importance of understanding biochemical
processes occurring in biological systems [10, 11].
Practical significance of the development of regio-
selective methods for the synthesis of 1,2,3-triazoles
in the absence of a catalyst (including physiological
conditions) is related, in particular, to the toxicity of
copper(I) catalysts for living cells despite wide
prospects in using bioorthogonal click chemistry
reactions [11, 12].
Me3Si), 10.13 s (1H, CHO), 15.47 br.s (NH). 13C NMR
spectrum, δC, ppm: –2.12 (Me3Si), 140.06 (C4), 152.40
(C5), 186.50 (CHO). Found, %: C 42.58; H 6.76;
N 24.71; Si 16.55. C6H11N3OSi. Calculated, %:
C 42.58; H 6.55; N 24.81; Si 16.60.
Triazolecarbaldehydes IIIb–IIId were synthesized
in a similar way.
4-Triethylgermyl-1H-1,2,3-triazole-5-carbalde-
hyde (IIIb). Yield 98%, colorless powder, mp 100–
102°C [7]. IR spectrum, ν, cm–1: 3110 (NH), 1680
(C=O). 1H NMR spectrum, δ, ppm: 0.80–1.20 m (15H,
Et3Ge), 10.21 s (1H, CHO), 14.32 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 4.64 and 9.12 (Et3Ge),
140.01 (C4), 152.42 (C5), 186.56 (CHO). Found, %:
C 42.36; H 6.80; Ge 28.65; N 16.55. C9H17GeN3O.
Calculated, %: C 42.25; H 6.70; Ge 28.37; N 16.42.
Only a few syntheses of N-substituted 1,2,3-tri-
azoles in aqueous medium in the absence of a catalyst
have been reported; these reactions require fairly
severe conditions (65–120°C, 12–24 h) [13]. We have
found only one example of successful regioselective
noncatalytic synthesis of triazoles in water at room
temperature [14]. It should be also noted that pro-
pynoates were used mainly as dipolarophiles in the
above syntheses. Up to now there were no data on the
efficiency and selectivity of reactions of azides with
heteroelement-substituted alkynes in water, while
addition of trimethylsilyl azide to alkynes in aqueous
medium was not reported at all.
1-Benzyl-4-trimethylsilyl-1H-1,2,3-triazole-
5-carbaldehyde (IIIc). Yield 96%, colorless crystals,
mp 39°C published data [16] for a mixture of 1,4- and
1,5-substituted isomers at a ratio of 93:7: mp 49–
51°C. IR spectrum, ν, cm–1: 1685 (C=O), 1250
1
(Si–CH3). H NMR spectrum, δ, ppm: 0.37 s (Me3Si),
5.91 s (2H, CH2), 7.25–7.34 m (5H, C6H5), 10.10 s
(1H, CHO). 13C NMR spectrum, δC, ppm: 0.27
(Me3Si), 52.84 (CH2); 125.99, 128.04, 129.07, 135.78
(Carom); 138.97 (C4), 153.14 (C5), 181.01 (CHO).
Found, %: C 59.73; H 6.07; N 16.01; Si 10.76.
C13H17N3OSi. Calculated, %: C 60.20; H 6.61;
N 16.20; Si 10.83.
To conclude, we have developed a highly efficient
procedure for the synthesis of N-substituted and
N-unsubstituted 4-trialkylsilyl(germyl)-1H-1,2,3-tri-
azole-5-carbaldehydes by reaction of 3-trimethylsilyl-
and 3-triethylgermylpropynals with trimethylsilyl and
benzyl azides in water at room temperature. The pro-
posed procedure is advantageous due to high yields,
regioselectivity, near-physiological conditions, the
absence of catalyst and by-products, insensitivity of
the products to atmospheric moisture and oxygen,
accessibility of initial reactants, and economy, which
meets the ideal synthesis and green chemistry require-
ments [15]. The obtained triazoles are biologically
important compounds, building blocks for organic syn-
thesis, and ligands for metal complexes.
1-Benzyl-4-triethylgermyl-1H-1,2,3-triazole-
5-carbaldehyde (IIId). Yield 96%, yellowish crystals,
1
mp 71°C. IR spectrum: ν 1690 cm–1 (C=O). H NMR
spectrum, δ, ppm: 1.02–1.13 m (15H, Et3Ge), 5.90 s
(2H, CH2), 7.21–7.33 m (5H, C6H5), 9.98 s (1H,
CHO). 13C NMR spectrum, δC, ppm: 4.89, 9.22
(Et3Ge), 52.94 (CH2); 127.89, 128.52, 129.08, 135.88
(Carom); 138.97 (C4), 152.92 (C5), 180.76 (CHO).
Found, %: C 55.12; H 6.42; Ge 20.65; N 12.20.
C16H23GeN3O. Calculated, %: C 55.54; H 6.70;
Ge 20.99; N 12.1.
4-Trimethylsilyl-1H-1,2,3-triazole-5-carbalde-
hyde (IIIa). A mixture of 0.08 g (0.6 mmol) of 3-tri-
methylsilylpropynal (Ia), 0.09 g (0.7 mmol) of tri-
methylsilyl azide, and 2 ml of distilled water was
stirred for 18 h at room temperature. The mixture was
extracted with ethyl acetate (3×10 ml), the extract was
dried over magnesium sulfate, the solvent was distilled
off, and the residue was kept under reduced pressure.
The product was chromatographically pure, and no
additional purification was necessary. Yield 0.09 g
(85%), colorless crystals, mp 188–189°C [9]. IR spec-
trum, ν, cm–1: 3100 (NH), 1690 (C=O), 1250
The IR spectra were recorded on a Bruker IFS-25
1
spectrometer. The H and 13C NMR spectra were
recorded on a Bruker DPX-400 spectrometer at 400.13
and 101.62 MHz, respectively, using DMSO-d6 as
solvent and hexamethyldisiloxane as internal refer-
ence. The elemental compositions were determined on
a Thermo Finnigan FlashEA 1112 Analyzer. The melt-
ing points were measured using a Micro-Hot-Stage
PolyTherm A melting point apparatus. The progress of
reactions and the purity of products were monitored by
1
(Si–CH3). H NMR spectrum, δ, ppm: 0.36 s (9H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012

DEMINA et al.
1584
p. 131; Piterskaya, Yu.L., Khramchikhin, A.V., Stadni-
chuk, M.D., Bel’skii, V.K., and Stash, A.I., Russ. J. Gen.
Chem., 1996, vol. 66, p. 1150.
TLC on Silufol UV-254 plates using chloroform–
methanol (10:) or hexane-diethyl ether (3:2) as eluent.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-01 024-a) and by the Interdisciplinary
Integration Project of the Siberian and Ural Divisions
of the Russian Academy of Sciences (project no. 1).
6. Piterskaya, Yu.L., Khramchikhin, A.V., and Stadni-
chuk, M.D., Russ. J. Gen. Chem., 1996, vol. 66, p. 1158.
7. Tret’yakov, E.V., Mareev, A.V., Demina, M.M., Roma-
nenko, G.V., Stas’, D.V., Medvedeva, A.S., and Ovcha-
renko, V.I., Izv. Ross. Akad. Nauk, Ser. Khim., 2009,
p. 1854.
REFERENCES
8. Huisgen, R., Angew. Chem., Int. Ed. Engl., 1963, vol. 2,
p. 565.
1. Wamhoff, H., Comprehensive Heterocyclic Chemistry,
Katritzky, A.R. and Rees, C.W., Eds., Oxford: Pergamon,
1984, vol. 5, p. 669; Alvarez, R., Velázquez, S., San-
Felix, A., Aquaro, S., De Clercq, E., Perno, C.-F.,
Karlsson, A., Balzarini, J., and Camarasa, M.J., J. Med.
Chem., 1994, vol. 37, p. 4185; Juríček, M.,
Kouwer, P.H.J., and Rowan, A.E., Chem. Commun., 2011,
vol. 47, p. 8740.
2. Tron, G.C., Pirali, T., Billington, R.A., Canonico, P.L.,
Sorba, G., and Genazzani, A.A., Med. Res. Rev., 2008,
vol. 28, p. 278; Colombo, M. and Bianchi, A., Molecules,
2010, vol. 15, p. 178.
9. Demina, M.M., Novopashin, P.S., Sarapulova, G.I.,
Larina, L.I., Smolin, A.S., Fundamenskii, V.S., Kasha-
ev, A.A., and Medvedeva, A.S., Russ. J. Org. Chem.,
2004, vol. 40, p. 1804.
10. Li, C.J., Chem. Rev., 2005, vol. 105, p. 3095;
Chanda, A. and Fokin, V.V., Chem. Rev., 2009, vol. 109,
p. 725.
11. Boyce, M. and Bertozzi, C.R., Nat. Methods, 2011,
vol. 8, p. 638.
12. Del Amo, D.S., Wang, W., Jiang, H., Besanceney, C.,
Yan, A.C., Levy, M., Liu, Y., Marlow, F.L., and Wu, P.,
J. Am. Chem. Soc., 2010, vol. 132, p. 16893.
13. Li, P. and Wang, L., Lett. Org. Chem., 2007, vol. 4,
p. 23; Wang, Z.X. and Qin, H.L., Chem. Commun.,
2003, p. 2450.
3. Krivopalov, V.P. and Shkurko, O.P., Usp. Khim., 2005,
vol. 74, p. 369; Tome, A.C., Science of Synthesis,
Storr, R.C. and Gilchrist, T.L., Eds., Stuttgart: Thieme,
2004, vol. 13, p. 415.
14. Li, Z., Seo, T.S., and Ju, J., Tetrahedron Lett., 2004,
4. Rostovtsev, V.V., Green, L.G., Fokin, V.V., and Sharp-
less, K.B., Angew. Chem., Int. Ed., 2002, vol. 41, p. 2596;
Tornøe, C.W., Christensen, C., and Meldal, M., J. Org.
Chem., 2002, vol. 67, p. 3057.
5. Coats, S.J., Link, J.S., Gauthier, D., and Hlasta, D.J.,
Org. Lett., 2005, vol. 7, p. 1469; Businelli, S., Di
Martino, E., and Zanirato, P., Arkivoc, 2001, part (i),
vol. 45, p. 3143.
15. Müller, T.J.J. and D’Souza, D.M., Pure Appl. Chem.,
2008, vol. 80, p. 609; Kustov, L.M. and Beletskaya, I.P.,
Ros. Khim. Zh., 2004, vol. 48, p. 3.
16. Khramchikhin, A.V. and Stadnichuk, M.D., Zh. Obshch.
Khim., 1991, vol. 61, p. 2012.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 12 2012