Synthesis of polyfunctional triethoxysilanes by 'click silylation'

Article abstract of DOI:10.1016/j.tetlet.2013.12.037

The copper-catalyzed 'click silylation' has been exploited for the chemical modification of γ-azidopropyltriethoxysilane (AzPTES) with a wide range of terminal alkynes (1a-1v) in a one-pot operation. The novel 1,2,3-triazole-triethoxysilane derivatives (2a-2v) were synthesized by this procedure and comprehensively characterized by IR spectra, ¹H and ¹³C NMR, and HRMS studies.

Full text of DOI:10.1016/j.tetlet.2013.12.037

Accepted Manuscript
Synthesis of polyfunctional triethoxysilanes by “click silylation”
Gurjaspreet Singh, Satinderpal Singh Mangat, Jandeep Singh, Aanchal Arora,
Ramesh K. Sharma
PII:
S0040-4039(13)02123-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.12.037
TETL 43951
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
23 August 2013
9 December 2013
14 December 2013
Please cite this article as: Singh, G., Mangat, S.S., Singh, J., Arora, A., Sharma, R.K., Synthesis of polyfunctional
triethoxysilanes by “click silylation”, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.
2
013.12.037
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Graphical abstract
Synthesis of polyfunctional triethoxysilanes by “click silylation”
a,
Gurjaspreet Singh *, Satinderpal Singh Mangat , Jandeep Singh , Aanchal Arora , Ramesh
a
a
a
b
K. Sharma
1

Synthesis of polyfunctional triethoxysilanes by “click silylation”
a,
Gurjaspreet Singh *,
a
Satinderpal Singh Mangat ,
a
Jandeep Singh ,
a
Aanchal Arora ,
b
Ramesh K. Sharma
a
Department of Chemistry, Panjab University, Chandigarh, 160014, India.
b
Central Instrumentation Laboratory, Panjab, University, Chandigarh, 160014, India.
*
Corresponding Author
Email: gjpsingh@pu.ac.in, Phone: +91-0172-2534428
2

Abstract
The copper-catalyzed “click silylation” has been exploited for the chemical modification of γ-
azidopropyltriethoxysilane (AzPTES) with a wide range of terminal alkynes (1a-1v) in a one-
pot operation. The novel 1,2,3-triazole-triethoxysilane derivatives (2a-2v) were synthesized
1 13
by this procedure and comprehensively characterized by IR spectra, H and C NMR and
HRMS studies.
Keywords:
Triethoxysilane
Click silylation
Functional alkyne
Heterocycle
[
3 3
CuBr(PPh ) ]
3

The extension of functional group versatility in organotriethoxysilanes (OTES) has
1
made it a flexible building block in organic synthesis. The OTES are key modules for the
,2
3
synthesis of well designed organic-inorganic hybrid materials having potential applications
4
as biosensors, surface group modifiers and supported catalysts . The syntheses of OTES
5
6
with enhanced properties require the functionalization of triethoxysilyl moiety with various
7
challenging substrates. This has been achieved either through an organometallic route or by
8
the hydrosilylation of olefins or dienes thus leading to complicated mixtures which
considerably affects isolation of products. Thus purification process requires skillful
9
techniques such as distillation or crystallization to avoid hydrolytic decomposition of
triethoxysilanes. Therefore, a revolutionary method is required to override these purification
steps to conventional total synthesis.
1
Initiated by Sharpless and co-workers, ‘click chemistry’ is well known for its
0
1
flexibility and is a valuable technique that has become a simple solution for long known
1
1
2
challenges. The research in this field is booming with the use of copper-catalyzed azide
alkyne cycloaddition reaction (CuAAC) (Scheme 1), that allows a safe and selective post
functionalization over other synthetic routes. This cross-coupling reaction has come up as an
important addition to the usual synthetic methodologies for the synthesis of OTES. The
integration of triethoxysilanes with heterocyclic triazole can extend its physical, chemical and
1
mechanical properties, and can provide a robust route for drug discovery, polymer
3
1
chemistry and sol-gel processes.
4
15
R
R
Cu(I)
N
R'
+
N3
R'
N
N
Scheme 1: General reaction Scheme for CuAAC
The restricted research on 1,2,3-triazole based OTES is primarily due to their
hygroscopic nature. As a part of our ongoing work, we herein report the synthesis of OTES
1
6
substituted with various terminal polyfunctionalized molecular entities via 1,2,3-triazole
linkage, that have made it a flagship reaction of the click chemistry. The quest for the
synthesis of polyfunctional OTES under milder reaction conditions has been exploited by the
1
7
use of Cu(I) and is gaining wide popularity under the term “click-silylation”.
4

1,17
Inspired by the pioneering work of Cattoen et al.
cycloaddition of alkyne functionalities has been carried out with 3-azidopropyltriethoxysilane
AzPTES) to obtain products having importance, well documented in research fields. This
methodology is based on [CuBr(PPh ]-THF/Et N system, under strict anhydrous conditions
on click silylation, the
(
3
)
3
3
for synthesis of hybrid silica precursors. Terminal alkyne functionalities (Table 1) such as N-
heterocycle, aniline, ether, acrylate, acetate, Schiff base, aldehyde and ketone group were
1
synthesized (Scheme 2) following the procedure described in the literature and have been
8
found to be in harmony with click strategy.
Nu
Br
K CO3
2
+
H-Nu
1a-1p
DMF
Nu: Nucleophile
O
S
O
O
(for 1q)
OH
O
1q-1s
O
O
(
for 1r)
Cl
(for 1o-1s)
Cl
Scheme 2: Synthesis of terminal alkynes from propargyl bromide and propargyl alcohol
The CuAAC reaction between these terminal alkynes and AzPTES afforded
polyfunctionalized triethoxysilanes (PfTES) in high yield with upto 95% conversion (Scheme
1
13
3
, Table 2). IR, NMR ( H, C) and High Resolution Mass spectroscopic details provide a
handful of information for the complete structure elucidation of PfTES. The downfield shift
of triplet due to -N CH2- protons from δ = 3.19 to δ = 4.19-4.31 ppm signifies the C-N bond
3
formation resulting into triazole (Figure 1). The sharing of two free π bonded electrons of
terminal alkyne to form a conjugated heterocycle drastically changes chemical shift from δ =
1
3
2
.0 to δ = 7.12-7.58 ppm. The parallel shifting of the peaks has been observed in C NMR
5

spectra as well. FT-IR spectroscopic data (Figure 2) show absorption due to N
3
functionality
-1
existing in uncyclized silane at 2096 cm whereas upon cyclization this peak disappears. The
-
blank region between 2140-2100 cm and the distinctive bands around 1650 cm points out
1
-1
to the successful cycloaddition of two molecular entities.
R
R
CuBr (PPh3)3
1a-v
N
3 Si(OEt)3
2a-v
+
Et N/THF
3
N
N
6
0oC
3
N3
Si(OEt)3
Scheme 3: General reaction Scheme for the synthesis of polyfunctional triethxoysilanes.
To determine the scope of this methodology, AzPTES was derivatized with N-
heterocycles such as morpholine, piperidine and phthalimide which have maintained the
1
9,20,21
interest of researchers through decades of historical development of organic synthesis.
So, 1:1 mixture of the N-heterocycle (1a-1c) and AzPTES was totted up in the beginning to
obtain the functionalized compounds (2a-2c) with desired moiety. The cycloaddition
o
proceeded smoothly under standard condition at 60 C for 5 h to give a small series of N-
2
2
heterocyclic derivatives in excellent yield. Furthermore, the aniline derivatives could be
selectively functionalized as this silylation method has proven to be very helpful to explore
the triazole substitution in material chemistry. Therefore, compounds (1d-1i) were chosen as
starting material for the synthesis of bulky aniline derivatives (2d-2i) in outstanding yield.
2
3
The use of benzylamine in bacterial degradation encouraged us to link this functionality (1j)
with sol-gel precursors for the synthesis of bio-inspired materials (2j).
Click silylation also proved to be an effective route to immobilize aldehyde and
ketone functionality on to silica supports, as it would play important role for protease
2
4
inhibition . The potent antimalarial activity of precursor compounds (1k-1n), on
incorporation of aldehyde or ketone side chain in 1,2,3-triazole (2k-2n), may lead to an
increase in anti-HIV activity. Aromatic Schiff base functionalities are amongst the most
2
popular photochromic compounds. Therefore, newly synthesized acetylenic Schiff bases
5
(
(
1o,1p) were substituted with OTES by click strategy in 15 h for the synthesis of compounds
2o,2p) with motive of further advancement in the field of photochemistry.
6

2
To further enlarge the scope, propargyl derivatives having ether (1q), acetate (1r),
6
27
2
N, N-dimethyl (1s), alkyl (1t) acrylate (1u) and cyclic olefin (1v) groups were also
8
29
30
31
used in this one pot labelling approach. In all cases, the reactions were carried out for 5 h at
o
0 C. The disappearance of azide peak in IR spectra clearly indicated the completion of
6
reaction in this short period. The synthesized silica precursors (2q-2v) may be useful as
secondary organic aerosols.
In the present work, we have synthesized the 1,2,3-triazole based PfTES (2a-2v). The
coupling of modified alkyne with AzPTES was achieved by CuAAC with keeping the
precursor as wide functional group to make this approach commercially attractive. This
methodology to synthesize triethoxysilanes is gaining wide popularity due to hooking of
polyfunctionalized groups that can be put to wonderful applications in fields of medicine,
optical sensors and material chemistry.
Acknowledgment
We thank the University Grant Commission (U.G.C) for the financial support. We also thank
Mr. Avtar Singh (SAIF, Panjab University, Chandigarh) for the NMR studies.
References
1
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Chem. 2011, 76, 7326-7333. (b) Cobos, O. D. L.; Fousseret, B.; Lejeune, M.;
Rossignol, F.; Colas, M. D.; Carrion, C.; Boissiere, C.; Ribot, F.; Sanchez, C.;
Cattoen, X.; Wong Chi Man, M.; Durand, J. O. Chem. Mater. 2012, 24, 4337-4342.
. Murata, M.; Ishikura, M.; Nagata, M.; Watanabe, S.; Masuda, Y. Org. Lett. 2002, 4,
2
3
4
5
1
843-1845.
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238. (b) Bekiari, V.; Lianos, P. Langmuir 1998, 14, 3459-3461.
5
. Jin, Z.; Zhang, X. B.; Xie, D. X.; Gong, Y. J.; Zhang, J.; Chen, X.; Shen, G. L.; Yu,
R. Q. Anal. Chem. 2010, 82, 6343-6346.
. Montanari, T.; Delgado, M. C. H.; Bevilacqua, M.; Busca, G.; Vargas, M. A. L.;
Alemany, L. J. J. Phys. Chem. B 2005, 109, 879-883. (b) Allen, C. G.; Baker, D. J.;
Albin, J. M.; Oertli, H. E.; Gillaspie, D. T.; Olson, D. C.; Furtak, T. E.; Collins, R. T.
Langmuir 2008, 24, 13393-13398.
7

6. (a) Zamboulis, A.; Moitra, N.; Moreau, J. J. E.; Cattoen, X.; Wong Chi Man, M. J.
Mater. Chem. 2010, 20, 9322-9338. (b) Corma, A.; Garcia, H. Adv. Synth. Catal.
2
006, 348, 1391-1412. (c) Ciriminna, R.; Cara, P. D.; Sciortino, M.; Pagliaro, M. Adv.
Synth. Catal. 2011, 353, 677-687.
7
8
9
1
. Trofimova, O. M.; Chernov, N. F.; Voronkov, M. G. Russ. Chem. Rev. 1999, 68, 287-
2
98.
. Marciniec, B. in Comprehensive Handbook on Hydrosilylation, Pergamon Press,
Oxford, 1992.
. Munoz, M. O.; Jaramillo, J. L.; Mateo, F. H.; Gonzalez, F. S. Adv. Synth. Catal. 2006,
3
48, 2410-2420.
0. (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 2001, 40,
004-2021. (b) Pagliai, F.; Pirali, T.; Grosso, E. D.; Brisco, R. D.; Tron, G. C.; Sorba,
2
G.; Genazzani, A. A. J. Med. Chem. 2006, 49, 467-470. (c) Whiting, M.; Tripp, J. C.;
Lin, Y. C.; Lindstrom, W.; Olson, A. J.; Elder, J. H.; Sharpless, K. B.; Fokin, V. V. J.
Med. Chem. 2006, 49, 7697-7710.
11. Iha, R. K.; Wooley, K. L.; Nystrom, A. M.; Burke, D. J.; Kade, M. J.; Hawker, C. J.
Chem. Rev. 2009, 109, 5620-5686.
12. Amblard, F.; Cho, J. H.; Schinazi, R. F. Chem. Rev. 2009, 109, 4207-4220
13. Solomun, T.; Mix, R.; Sturm, H. Appl. Mater. Interfaces 2000, 2, 2171-2174.
14. Ackermann, L.; Potukuchi, H. K. Org. Biomol. Chem. 2010, 8, 4503-4513.
15. (a) Naciri, J.; Fang, J. Y.; Moore M.; Shenoy, D.; Dulcey, C. S.; Shashidhar R. Chem.
Mater. 2000, 12, 3288-3295. (b) Du, K.; Wathuthanthri, I.; Liu, Y.; Xu, W.; Choi C.
H. Appl. Mater. Interfaces 2012, 4, 5505-5514.
16. General reaction procedure for the click silylation:
To a 50 ml two-necked round bottom flask with alkyne function (2 mmol), azide function (2
mmol/alkyne function), [CuBr(PPh ] (0.01 mmol/alkyne function), triethylamine (2 ml),
3 3
)
and THF (2 ml) under nitrogen atmosphere and then the mixture was stirred at 60 °C for 5 h.
The reaction mixture was allowed to cool, and the solvents were removed under vacuum
followed by addition of hexane. The mixture was filtered and washed with 2 x 5 ml of
hexane. The concentration of the filtrate under reduced pressure afforded the title compound
in good to excellent yield.
-
1
2
a. Yield: 95%; IR (Neat, cm ) 2971, 2926, 2889, 2812, 1453, 1389, 1325, 1285, 1215,
164, 1114, 1100, 1070, 1003, 954, 913, 865, 784; NMR (400 MHz, CDCl , 25 °C) δ = 7.43
CH , J = 7.0 Hz),
1
3
H
(
s, 1H, Tz-H), 4.28 (t, 2H, -NCH
2
CH
2
-, J = 7.2 Hz), 3.74 (q, 6H, -OCH
2
3
8

3
4
2
.63 (t, 4H, -OCH
2
CH
2
N-, J = 4.6 Hz), 3.59 (s, 2H, -NCH
2
-), 2.44 (t, 4H, -NCH
2 2
CH O-, J =
.4 Hz), 1.99 - 1.91 (m, 2H, -CCH
2
C-), 1.14 (t, 9H, -OCH
2
CH , J = 7.5 Hz), 0.53 - 0.51 (m,
3
+
= 143.9, 122.6, 66.8, 58.5, 53.7, 53.4, 52.4, 24.2, 18.2, 7.4. HRMS (ES )
H, -SiCH
2
-). δ
C
+
Si [M + H] 373.2271, found 373.2276.
calcd for C16
H
32
N
4
O
4
-
1
2
b. Yield: 93%; IR (Neat, cm ) 2962, 1718, 1395, 1258, 1215, 1073, 864, 790; NMR (400
MHz, CDCl , 25 °C) δ = 7.76 (dd, 2H, Ar-H), 7.63 (dd, 2H, Ar-H), 7.54 (s, 1H, Tz-H), 4.91
s, 2H, -NCH -), 4.24 (t, 2H, -N CH CH -, J = 8.0 Hz), 3.71 (q, 6H, -OCH CH , J = 8.0 Hz),
.95 - 1.88 (m, 2H, -CCH C-), 1.12 (t, 9H, -OCH CH , J = 8.0 Hz), 0.52 - 0.48 (m, 2H, -
3
H
(
2
3
2
2
2
3
1
2
2
3
SiCH
2
-). δ
C
= 166.5, 133.0, 131.9, 122.4, 121.8, 57.4, 51.5, 32.0, 23.1, 17.2, 6.3. HRMS
+
ES ) calcd for C20
+
Si [M + Na] 455.1726, found 455.1705.
(
H
28
N
4
O
5
-1
2
c. 2j.Yield: 93%; IR (Neat, cm ) 2972, 2928, 1082, 1439, 1389, 1295, 1164, 1100, 991,
54, 861, 782; NMR (300 MHz, CDCl , 25 °C) δ = 7.41 (s, 1H, Tz-H), 4.26 (t, 2H, -
CH CH -, J = 7.1 Hz), 3.74 (q, 12H, -OCH CH , J = 7.2 Hz), 3.55 (s, 2H, -NCH -), 2.37
m, 4H, -CCH CH N-), 1.99-1.90 (m, 2H, -CCH C-), 1.51-1.49 (m, 4H, -CCH CN-), 1.38 -
.36 (m, 2H, -CH CH C-), 1.14 (t, 18H, -OCH CH , J = 7.1 Hz), 0.52 - 0.47 (m, 2H, -SiCH
9
3
H
N
3
2
2
2
3
2
(
2
2
2
2
1
2
2
2
3
2
-
+
= 139.1, 125.2, 57.9, 52.5, 52.1,51.9, 23.7, 23.5, 23.2, 22.4, 17.9, 7.1. HRMS (ES )
)
. δ
C
+
Si [M + 1] 371.2478, found 371.2471.
calcd for C20
H
28
N
4
O
5
-
1
2
d. Yield: 94%; IR (Neat, cm ) 2972, 2885, 1599, 1505, 1389, 1294, 1215, 1164, 1071, 953,
8
77, 780; NMR (300 MHz, CDCl , 25 °C) δ = 7.33 (s, 2H, Tz-H), 7.14 - 7.08 (m, 2H, Ar-
3
H
H), 6.80 (d, 1H, Ar-H), 6.67 - 6.64 (m, 1H, Ar-H), 6.60 - 6.58 (m, 1H, Ar-H) 4.60 (s, 4H, -
NCH -), 4.21 (t, 4H, -N CH CH -, J = 7.2 Hz), 3.72 (q, 12H, -OCH CH , J = 5.9 Hz), 1.94 -
.88 (m, 4H, -CCH C-), 1.13 (t, 18H, -OCH
2
3
2
2
2
3
1
2
2
CH
3
2
, J = 7.0 Hz), 0.51 - 0.47 (m, 4H, -SiCH -).
+
= 148.3, 129.1, 117.8, 113.8, 58.4, 52.2, 46.7, 24.2, 18.3, 7.4. HRMS (ES ) calcd for
δ
C
+
[M + Na] 686.3493, found 686.3443.
C
30
H
53
N
7
O
6
Si
2
-
1
2
e. Yield: 93%; IR (Neat, cm ) 2966, 2926, 2868, 1654, 1599, 1493, 1452, 1373, 1343,
152, 1107, 1072, 952, 879, 780; NMR (300 MHz, CDCl , 25 °C) δ = 7.17 -7.09 (m, 2H,
-), 4.19 (t, 2H, -N CH CH
, J = 7.2 Hz), 2.92 (s, 3H, -NCH -), 1.91 - 1.83 (m, 2H,
1
3
H
Ar-H, 1H, Tz-H ), 6.69 - 6.60 (m, 3H, Ar-H), 4.55 (s, 2H, -NCH
2
3
2
2
-
,
J = 7.1 Hz), 3.68 (q, 6H, -OCH
2
CH
3
3
-
CCH C-), 1.12 (t, 9H, -OCH CH
2
2
3
, J = 7.1 Hz), 0.44 - 0.42 (m, 2H, -SiCH
2
C
-). δ = 149.0,
9

+
45.0, 129.2, 121.4, 117.3, 113.1, 58.3, 52.1, 48.7, 38.3, 24.0, 18.1, 7.2. HRMS (ES ) calcd
1
+
Si [M + H] 393.2321, found 393.2302.
for C19
H
32
N
4
O
3
-1
2
f. Yield: 86%; IR (Neat, cm ) 2974, 2926, 2887, 1597, 1498, 1438, 1389, 1294, 1215, 1164,
099, 1072, 954, 747; NMR (300 MHz, CDCl , 25 °C) δ = 7.28 (s, 2H, Tz-H), 7.09 - 6.90
-), 4.24 (t, 4H, -N CH CH -, J =
, J = 7.2 Hz), 1.93 - 1.71 (m, 4H, -CCH C-), 1.17 (t, 18H, -
1
3
H
(
m, 2H, Ar-H), 6.69-6.79 (m, 2H, Ar-H), 4.52 (s, 4H, -NCH
2
3
2
2
8
.2 Hz), 3.75 (q, 12H, -OCH
2
CH
3
2
OCH CH , J = 7.1 Hz), 0.50 - 0.29 (m, 4H, -SiCH
3
2
2
-). δ
C
= 146.7, 144.6, 129.0, 122.0, 121.9,
+
15.0, 114.1, 58.3, 52.4, 46.8, 46.0, 24.0, 18.2, 7.3. HRMS (ES ) calcd for C30
1
H
52ClN
7
O
6
Si
2
+
M + H] 698.3284, found 698.3294.
[
-
1
2
g. Yield: 91%; IR (Neat, cm ) 2973, 2927, 2887, 1595, 1490, 1438, 1389, 1294, 1224,
169, 1098, 1072, 954, 748; NMR (400 MHz, CDCl , 25 °C) δ = 7.35 (s, 1H, Tz-H), 6.76
-), 4.21 (t, 4H, -N CH CH -, J = 7.1 Hz),
.70 (q, 12H, -OCH2CH3, J = 7.0 Hz), 1.96 - 1.83 (m, 4H, -CCH C-), 1.11 (t, 18H, -
1
3
H
(
dd, 4H, Ar-H, J = 11.7, 7.1 Hz), 4.51 (s, 4H, -NCH
2
3
2
2
3
2
OCH
2
CH
3
, J = 7.0 Hz), 0.50 - 0.41 (m, 4H, -SiCH
2
-). δ
C
= 157.0, 154.7, 144.5, 131.7, 128.3,
+
22.0, 115.5, 115.4, 115.1, 58.2, 52.1, 47.2, 23.9, 18.0, 7.0. HRMS (ES ) calcd for
1
+
C
30 7 6 2
H52FN O Si [M + Na] 704.3399, found 704.3337.
-
1
2
1
6
7
h. Yield: 89%; IR (Neat, cm ) 2975, 2926, 2886, 1500, 1438, 1389, 1293, 1241, 1165,
101, 1076, 957, 907, 780; NMR (300 MHz, CDCl , 25 °C) δ = 7.29 (s, 2H, Tz-H), 6.83 -
.72 (m, 2H), 6.66 (d, 2H, J = 8.9 Hz), 4.43 (s, 4H, -NCH -), 4.20 (t, 4H, -N CH CH -, J =
.0 Hz), 3.70 (q, 12H, -OCH CH , J = 7.1 Hz), 3.60 (s, 3H, -OCH ) 1.89 - 1.96 (m, 4H, -
C-), 1.13 (t, 18H, -OCH CH , J = 7.5 Hz), 0.51 - 0.38 (m, 4H, -SiCH -). δ = 132.1,
3
H
2
3
2
2
2
3
3
CCH
2
2
3
2
C
+
31.2, 128.6, 123.2, 121.8, 58.4, 53.7, 52.2, 46.9, 24.1, 18.2, 7.3. HRMS (ES ) calcd for
1
+
[M + Na] 716.3599, found 716.3560.
C
31
H
55
N
7
O
7
Si
2
-
1
2
1
7
7
i. Yield: 88%; IR (Neat, cm ) 2975, 2928, 2887, 1502, 1437, 1388, 1293, 1241, 1165, 1100,
076, 958, 907, 784; NMR (300 MHz, CDCl , 25 °C); NMR (300 MHz, CDCl , 25 °C) δ
.58 - 7.28 (m, 2H), 6.83 - 6.72 (m, 4H), 4.43 (s, 4H, -NCH -), 4.20 (t, 4H, -N CH CH -, J =
.0 Hz), 3.70 (q, 12H, J = 7.2 Hz), 1.89-1.97 (m, 4H, -CCH C-), 1.13 (t, 18H, -OCH CH , J
3
3
H
=
2
3
2
2
2
2
3
=
7.5 Hz), 0.51 - 0.38 (m, 4H, -SiCH
2
-). δ
C
= 132.4, 128.4, 123.2, 121.2, 120.9, 58.4, 52.2,
+
+
[M + Na] 716.3599, found
4
7
6.8, 24.2, 18.4, 7.4. HRMS (ES ) calcd for C31
16.3567.
H
55
N
7
O
7 2
Si
1
0

-1
2
j. Yield: 88%; IR (Neat, cm ) 2973, 2927, 2888, 1438, 1390, 1293, 1257, 1216, 1164, 1073,
57, 748; NMR (300 MHz, CDCl , 25 °C) δ = 7.53 (s, 2H, Tz-H), 7.29 - 7.15 (m, 5H, Ar-
CH CH -, J = 8.2 Hz), 3.72 (q, 12H, -OCH CH , J = 7.2 Hz), 3.55 (m,
-), 1.99 -1.94 (m, 4H, -CCH C-), 1.15 (t, 18H, -OCH CH , J = 7.1 Hz), 0.54 -
.49 (m, 4H, -SiCH -). δ = 132.1, 131.8, 128.9, 128.2, 126.9, 123.1, 58.2, 52.1, 31.4, 24.1,
9
3
H
H), 4.29 (t, 4H, -N
3
2
2
2
3
6
0
2
6
H, -NCH
2
2
2
3
2
C
+
2.7, 18.1, 13.9, 7.3. HRMS (ES ) calcd for C31
+
55 7 6 2
H N O Si [M + H] 678.3830, found
78.3873.
-
1
2
1
δ
k. Yield: 94%; IR (Neat, cm ) 2972, 2926, 2885, 1674, 1598, 1576, 1507, 1419, 1389,
358, 1305, 1271, 1247, 1099, 1072, 1050, 999, 861, 783; NMR (300 MHz, CDCl , 25 °C)
= 7.64 (dd, 1H, Ar-H), 7.57 (s, 1H, Tz-H), 7.41 - 6.92 (m, 3H, Ar-H), 5.24 (s, 2H, -OCH
CH CH -, J = 7.2 Hz), 3.73 (q, 6H, -OCH CH , J = 7.0 Hz,), 2.49 (s, 3H, -
-), 1.99 - 1.91 (m, 2H, -CCH C-), 1.14 (t, 9H, -OCH CH , J = 7.1 Hz), 0.54 - 0.49 (m,
H, -SiCH -). δ = 199.4, 158.3, 144.1, 133.4, 130.3, 128.7, 122.8, 121.2, 113.0, 62.5, 58.4,
8.0, 31.7, 24.1, 18.0, 13.9, 7.2. HRMS (ES ) calcd for C20
3
H
2
-
)
, 4.31 (t, 2H, -N
3
2
2
2
3
CCH
3
2
2
3
2
4
2
C
+
+
31 3 5
H N O Si [M + H] 444.1930,
found 444.1940.
-
1
2
1
1
l. Yield: 93%; IR (Neat, cm ) 2972, 2926, 2883, 1685, 1597, 1481, 1456, 1389, 1284, 1236,
213, 1189, 1162, 1099, 1071, 998, 953, 782; NMR (300 MHz, CDCl , 25 °C) δ = 9.80 (s,
H, -HC=O), 7.75 (d, 2H, Ar-H), 7.56 (s, 1H, Tz-H), 7.03 (d, 2H, Ar-H), 5.22 (s, 2H, -OCH
CH CH -, J = 7.1 Hz,), 3.72 (q, 6H, -OCH CH -, J = 7.0 Hz), 2.01 - 1.91
C-), 1.14 (t, 9H, -OCH CH , J = 7.0 Hz), 0.52 - 0.47 (m, 2H, -SiCH -). δ
90.1, 163.2, 132.0, 130.6, 122.8, 115.2, 62.3, 58.4, 52.4, 24.2, 18.3, 7.4. HRMS (ES ) calcd
3
H
2
-
)
(
, 4.30 (t, 2H, -N
m, 2H, -CCH
3
2
2
2
3
2
2
3
2
C
=
+
1
+
29 3 5
for C19H N O Si [M + Na] 430.1774, found 430.1770.
-
1
2
1
δ
m. Yield: 95%; IR (Neat, cm ) 2972, 2927, 2885, 1675, 1597, 1576, 1509, 1421, 1389,
355, 1305, 1271, 1250, 1099, 1071, 1050, 999, 861, 781; NMR (300 MHz, CDCl , 25 °C)
= 7.82 (d, 2H, Ar-H), 7.58 (s, 1H, Tz-H), 6.94 (d, 2H, Ar-H), 5.18 (s, 2H, -OCH -), 4.30
CH CH -, J = 6.9 Hz), 3.74 (q, 6H, -OCH CH , J = 8.8 Hz,), 2.46 (s, 3H, -CCH -),
.01 - 1.94 (m, 2H, -CCH C-), 1.14 (t, 9H, -OCH CH3, J = 8.7 Hz), 0.53 - 0.47 (m, 2H, -
3
H
2
(
t, 2H, -N
3
2
2
2
3
3
2
2
2
SiCH
2
-). δ
C
195.7, 162.1, 132.0, 130.8, 130.5, 128.4, 114.4, 62.0, 58.3, 26.0, 24.1, 18.2, 7.3.
+
HRMS (ES ) calcd for C20
+
Si [M + H] 444.1930, found 444.1942.
H
31
N
3
O
5
1
1

-
1
2
1
1
n. Yield: 94%; IR (Neat, cm ) 2975, 2923, 2884, 1685, 1597, 1480, 1454, 1389, 1283,
236, 1213, 1187, 1162, 1099, 1071, 998, 954, 782; NMR (300 MHz, CDCl , 25 °C) δ
0.36 (s, 1H, -HC=O), 7.73 - 7.69 (m, 2H, Ar-H), 7.46 (s, 1H, Tz-H), 7.12 - 7.10 (m, 1H, Ar-
-), 4.31 (t, 2H, -N CH CH -, J = 7.1 Hz),
-, J = 8.6 Hz), 1.99 - 1.95 (m, 2H, -CCH C-), 1.13 (t, 9H, -OCH CH
J = 8.5 Hz), 0.52 - 0.47 (m, 2H, -SiCH -). δ = 188.8, 160.4, 135.6, 128.5, 125.7, 121.0,
12.5, 62.4, 58.2, 52.2, 23.9, 18.1, 7.2. HRMS (ES ) calcd for C19
30.1774, found 430.1768.
3
H
=
H), 6.97 - 6.93 (m, 1H, Ar-H), 5.25 (s, 2H, -OCH
2
3
2
2
3
.72 (q, 6H, -OCH
2
CH
3
2
2
3
,
2
C
+
+
1
4
29 3 5
H N O Si [M + Na]
-1
2
o. Yield: 93%; IR (Neat, cm ) 2972, 2884, 1674, 1618, 1599, 1481, 1454, 1388, 1363,
285, 1241, 1207, 1186, 1161, 1100, 1072, 1001, 954, 876, 753; NMR (300 MHz, CDCl , 25
= 8.78 (s, 1H, -CH=N), 8.10 - 6.95 (m, 8H, Ar-H), 7.48 (s, 1H, Tz-H), 5.24 (s, 2H, -
-), 4.26 (t, 2H, -N CH CH -, J = 7.2 Hz), 3.67 (q, 6H, -OCH CH , J = 7.0 Hz), 1.98 -
C-), 1.12 (t, 9H, -OCH CH , J = 7.1 Hz), 0.50 - 0.45 (m, 2H, -SiCH -).
= 158.3, 156.3, 152.8, 136.0, 132.7, 129.1, 127.8, 125.7, 122.8, 121.5, 121.0, 113.1, 112.8,
1
3
°C) δ
H
OCH
2
3
2
2
2
3
1
.89 (m, 2H, -CCH
2
2
3
2
δ
6
4
C
+
2.6, 58.4, 52.4, 30.7, 24.1, 18.1, 7.3. HRMS (ES ) calcd for C25
+
H
34
N
4
O
4
Si [M + H]
83.2427, found 483.2237.
-
1
2
p. Yield: 88%; IR (Neat, cm ) 2931, 2873, 1682, 1598, 1582, 1558, 1482, 1456, 1431,
1
352, 1259, 1210, 1161, 1121, 1094, 1050, 1013, 937, 908, 876, 754; NMR (300 MHz,
CDCl
3
, 25 °C) δ
s, 2H, -OCH -), 4.27 (t, 2H, -N
.99 - 1.90 (m, 2H , -CCH C-), 1.12 (t, 9H, -OCH
H
= 9.48 (s, 1H, -CH=N), 8.40 - 6.95 (m, 7H, Ar-H), 7.58 (s, 1H,Tz-H), 5.29
CH CH -, J = 7.2 Hz), 3.70 (q, 6H, -OCH CH , J = 7.1 Hz),
CH , J = 7.2 Hz), 0.52 - 0.46 (m, 2H, -
(
2
3
2
2
2
3
1
2
2
3
SiCH
2
-). δ
C
= 188.9, 160.5, 158.9, 158.6, 137.7, 135.7, 133.3, 128.8, 128.2, 122.7, 121.3,
+
13.1, 112.9, 88.9, 62.8, 58.5, 52.5, 24.2, 18.4, 7.5. HRMS (ES ) calcd for C24
1
H
33
N
5
O
4
Si [M
+
H] 484.2380, found 484.2361.
+
-1
2
q. Yield: 94%; IR (Neat, cm ) 2972, 2933, 2885, 1440, 1389, 1260, 1164, 954, 787; NMR
300 MHz, CDCl , 25 °C) δ = 7.48 (s, 1H, Tz-H), 4.51 (s, 2H, -OCH -), 4.29 (t, 2H, -
-, J = 7.2 Hz,), 3.74 (q, 6H, -OCH CH -, J = 7.0 Hz), 3.34 (s, 3H, -OCH ), 1.91 -
C-), 1.15 (t, 9H, -OCH CH
(
3
H
2
N
3
CH
2
CH
2
2
3
3
1
.91 (m, 2H, -CCH
2
2
3
, J = 7.0 Hz), 0.55 - 0.51 (m, 2H, -SiCH
2
-) δ
C
+
144.9, 122.3, 66.0, 58.5, 58.3, 52.4, 24.2, 18.3, 7.4. HRMS (ES ) calcd for C13
=
H
27
N
3
O
4
Si
+
M + Na] 340.1667, found 340.1650.
[
1
2

-
1
2
9
4
2
1
r. Yield: 93%. IR (Neat, cm ) 2974, 2929, 2892, 1741, 1439, 1389, 1366, 1230, 1164, 1073,
56, 784; NMR (300 MHz, CDCl , 25 °C) δ = 7.52 (s, 1H, Tz-H), 5.11 (s, 2H, -OCH -),
.28 (t, 2H, -N CH CH -, J = 5.6 Hz,), 3.73 (q, 6H, -OCH CH -, J = 6.9 Hz), 2.0 - 1.93 (m,
H, -CCH C-), 1.15 (t, 9H, -OCH CH , J = 6.8 Hz), 0.53 - 0.48 (m, 2H, -SiCH -). δ = 170.3,
3
H
2
3
2
2
2
3
2
2
3
2
C
+
32.0, 128.3, 123.7, 121.1, 58.2, 57.4, 52.1, 23.6, 20.5, 18.1, 7.2. HRMS (ES ) calcd for
+
Si [M + Na] 368.1617, found 368.1614.
C
14
H
27
N
3
O
5
-1
2
s. Yield: 93%. IR (Neat, cm ) 2973, 2929, 2887, 1724, 1634, 1439, 1407, 1295, 1267, 1180,
045, 957, 809, 782; NMR (300 MHz, CDCl , 25 °C) δ = 7.58 (s, 1H, Tz-H), 6.37 (d, 1H, -
C=CH-, J = 17.1 Hz), 6.11 - 6.02 (m, 1H, -H C=CH-), 5.78 (d, 1H, -H C=CH-, J = 10.5
Hz), 5.24 (s, 2H, -OCH -), 4.29 (t, 2H, -N CH CH -, J = 7.2 Hz), 3.74 (q, -OCH CH -, 6H, J
6.9 Hz,), 1.98 - 1.93 (m, 2H, -CCH C-), 1.15 (t, 9H, -OCH CH , J = 6.9 Hz), 0.56 - 0.55
1
3
H
H
2
2
2
2
3
2
2
2
3
=
2
2
3
(
m, 2H, -SiCH
2
-). δ
C
= 165.3, 142.3, 130.8, 128.1, 123.6, 58.2, 57.5, 52.1, 24.0, 18.1, 7.3.
+
HRMS (ES ) calcd for C15
+
Si [M + Na] 380.1617, found 380.1694.
H
27
N
3
O
5
-
t. Yield: 95%. IR (Neat, cm ) 3132, 2971, 2927, 2884, 1551, 1438, 1389, 1294, 1214, 1165,
1
2
1
1
099, 1072, 954, 876, 780; H NMR (300 MHz, CDCl
CH CH -, J = 7.1 Hz), 3.72 (q, 6H, -OCH CH -, J = 7.0 Hz,), 2.61 (t, J = 7.5 Hz, 2H),
.07-1.78 (m, 2H, -CH C-), 1.6 - 1.59 (m, 2H, -CCH C-), 1.14 (t, 9H, -OCH CH , J = 7.0
3
H
): δ = 7.19 (s, 1H, Tz-H), 4.24 (t, 2H,
-
N
3
2
2
2
3
2
2
2
2
3
Hz), 0.91 (t, 3H, -CCH
3
J = 7.3 Hz), 0.57 - 0.35 (m, 2H, -SiCH
2
-). δ
C
= 132.2, 128.5, 58.3,
+
2.1, 27.6, 24.2, 22.6, 18.2, 13.7, 7.4. HRMS (ES ) calcd for C14
+
5
3
H
29
N
3
O
3
Si [M + Na]
38.1875, found 338.1828.
u. Yield: 95%. IR (Neat, cm ) 3133, 2955, 2823, 1655, 1587, 1534, 1432, 1351, 1218,
-1
2
-
1 1
1
034, 886, 763, 696 cm . H NMR (300 MHz, CDCl
CH CH -, J = 6.9 Hz), 3.72 (q, 6H, -OCH CH -, J = 7.0 Hz), 3.51 (s, 2H, -CH
H, -NCH ), 1.99 - 1.81 (m, 2H, -CH C-), 1.12 (t, 9H, -OCH
m, 2H, -SiCH
3
): δ
H
= 7.48 (s, 1H, Tz-H), 4.28 (t, 2H, -
N
3
2
2
2
3
2
N-), 2.18 (s,
6
3
2
2
CH
3
, J = 7.0 Hz), 0.58 - 0.42
+
(
2
-). δ
C
= 144.6, 122.1, 58.3, 54.1, 52.1, 45.9, 24.0, 17.1, 7.1. HRMS (ES )
+
Si [M + H] 331.2165, found 331.2171.
calcd for C14
H
30
N
4
O
3
-
1
v. Yield: 94%. IR (Neat, cm ) 2975, 2928, 1437, 1390, 1294, 1221 ,1165, 1101, 1075, 957,
2
1
9
07, 782; H NMR (300 MHz, CDCl
3
) δ
-, J = 7.1 Hz), 3.74 (q, 6H, -OCH
-), 2.12 (dd, 2H, -CCH - J = 5.9, 2.6 Hz), 2.02-1.84 (m, 2H, -CH
C-), 1.63 - 1.54 (m, 2H, -CCH C-), 1.14 (t, 9H, -OCH CH , J = 7.0 Hz), 0.61 -
H
= 7.33 (s, 1H, Tz-H), 6.50-6.36 (m, 1H, -CH=CH-
CH -, J = 7.0 Hz), 2.38-2.25 (m,
C-), 1.73-1.66
)
, 4.25 (t, 2H, -N
3
CH
2
CH
2
2
3
2
H, =CCH
2
2
2
(
m, 2H, -CCH
2
2
2
3
1
3

0
1
.46 (m, 2H, -SiCH
2
-). δ
C
= 148.9, 127.6, 124.2, 118.4, 58.2, 53.3, 26.4, 25.2, 22.5, 22.2,
+
8.1, 7.2. HRMS (ES ) calcd for C17
+
Si [M + Na] 376.2031, found 376.2080.
H
31
N
3
O
4
1
7. Moitra, N.; Moreau, J. J. E.; Cattoen, X.; Man, M. W. C. Chem. Comm. 2010, 46,
416-8418.
8. (a) Harrison G. A.; Zhou, S.; Hines, J. V.; Bergmeier, S. C. J. Comb. Chem. 2010, 12,
91-496. (b) Cantet, A. C.; Carreyre, H.; Gesson, J. P.; Jouannetaud, M. P.; Renoux,
8
1
4
B. J. Org. Chem. 2008, 73, 2875-2878. (c) Henderson, M. A.; Luo, J.; Oliver, A.;
McIndoe, J. S. Organometallics 2011, 30, 5471-5479. (d) Hans, R. H.; Guantai, E.
M.; Lategan, C.; Smith, P. J.; Wanc, B.; Franzblau, S. G.; Gut, J.; Rosenthal, P. J.;
Chibale, K. Bioorg. Med. Chem. Lett. 2010, 20, 942-944. (e) Mames, A.;Stecko, S.;
Mikozajczyk, P.; Soluch, M.; Furman, B.; Chmielewski, M. J. Org. Chem. 2010, 75,
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580-7587. (f) Nandini R. P.; Dubhashi, D. S. Arch. Appl. Sci. Res. 2010, 2, 72-84.
g) Lang, A. S.; Neubig, A.; Sommer, M.; Thelakkat, M. Macromolecules 2010, 43,
001-7010.
(
7
1
2
2
2
9. Awwad, A. M. J. Chem. Eng. Data 2008, 53, 307-309.
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2
25. (a) Sporkel, L.; Cui, G.; Thiel, W. J. Phys. Chem. 2013, 117, 4574-4583. (b) Lu, J.;
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Captions of figures and Tables:
1
Figure 1: Comparison of H NMR spectra between cyclized silane and AzPTES.
Figure 2: FT-IR spectra of AzPTES and polyfunctional triethoxysilanes (2a-2v).
Table 1: Clickable terminal alkynes (1a-1v).
Table 2: Synthesized polyfunctional triethoxysilanes (2a-2v).
1
5

1
Figure 1: Comparison of H NMR spectra between cyclized silane and AzPTES
1
6

This blank region clearly
N3
represents the cyclized product
AzPTES
2v
2u
2t
2s
2r
2q
2
o,2p
l,2n
k,2m
2
2
2j
2h,2i
2f,2g
2d,2e
2c
2b
2a
3
500
3000
2500
2000
1500
1000
500
Figure 2: FT-IR spectra of AzPTES and polyfunctional triethoxysilanes (2a-2v)
1
7

O
O
N
N
N
N
1a
1c
1d
O
N
N
N
Cl
N
F
1e
1g
1h O
1f
O
O
N
O
N
1i
1j
O
O
O
O
O
1l
1m
1n
O
O
N
N
N
O
O
O
O
1q
1p
1o
O
N
O
1v
1s
1u
1t
Table 1: Clickable terminal alkynes (1a-1v)
1
8

Terminal Reaction
Product
Compound Yield (%)
name
Alkyne
Time (h)
O
N
3
N
N
Si(OEt)3
1
a
5
2a
2b
95
N
O
3
N
N
Si(OEt)3
1
b
5
93
93
N
N
O
3
N
Si(OEt)3
2c
N
1
c
20
20
N
N
N
3
N
Si(OEt)3
N
2d
94
N
1
d
2
3
N
Si(OEt)3
N
1
e
10
10
2e
2f
93
86
N
N
3
N
Si(OEt)3
1
f
Cl
N
N
N
2
3
N
Si(OEt)3
1
g
10
10
F
N
2g
2h
91
89
N
N
2
3
N
Si(OEt)3
N
1
h
N
N
2
O
1
9

3
N
Si(OEt)3
1
i
10
O
N
2i
2j
88
88
N
N
2
3
N
Si(OEt)3
1j
N
N
N
10
2
O
3
N
Si(OEt)3
O
2k
94
N
N
1k
5
3
O
N
Si(OEt)3
O
1
l
N
N
2l
93
95
5
5
3
O
O
N
Si(OEt)3
O
1
m
2m
N
N
O
3
N
Si(OEt)3
1
n
5
2n
94
N
N
N
3
N
Si(OEt)3
O
N
N
1o
15
2o
93
2
0

N
N
3
N
Si(OEt)3
O
N
N
1
1
p
q
15
2p
2q
88
94
3
N
Si(OEt)3
5
O
N
N
O
3
N
Si(OEt)3
1
r
5
5
5
5
5
2r
2s
2t
93
93
95
95
94
O
N
N
O
3
N
Si(OEt)3
1
s
O
N
N
3
N
Si(OEt)3
1
t
N
N
3
N
Si(OEt)3
N
1
u
2u
2v
N
N
3
N
Si(OEt)3
1v
N
N
Table 2: Synthesized polyfunctional triethoxysilanes (2a-2v).
2
1