Synthesis, characterization and antibacterial studies of schiff based 1,2,3-triazole bridged silatranes

Article abstract of DOI:10.1016/j.jorganchem.2018.06.024

A single step Cu (I) assisted click silylation reaction had been used for the synthesis of novel Schiff based 1,2,3-triazole bridged silatrane (SBTBS)-scaffolds (5a-5f) using polyfunctionalised Schiff based 1,2,3-triazole bridged organotriethoxysilanes (SBTBOTS) (4a-4f) as precursors. These compounds were synthesized in excellent yields using an economical, simple and biocompatible synthetic procedure and their structures were characterized by various spectroscopy methods such as IR, NMR (1H and 13C) and elemental analysis. The presence of different pharmacologically active segments into a single triazole unit can result into impressive achievement in their bioactivity. So, antibacterial studies of the silatranes (5a-5f) were also carried out and it was observed that all the compounds showed potential antibacterial activity. The results also indicate that activity of compound 5f is even comparable to the standard drug, cefepime.

Full text of DOI:10.1016/j.jorganchem.2018.06.024

Accepted Manuscript
Synthesis, characterization and antibacterial studies of schiff based 1,2,3-triazole
bridged silatranes
Gurjaspreet Singh, Jasbhinder Singh, Akshpreet Singh, Jandeep Singh, Manoj
Kumar, Kshitiz Gupta, Sanjay Chhibber
PII:
S0022-328X(18)30520-5
10.1016/j.jorganchem.2018.06.024
JOM 20483
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 17 April 2018
Revised Date: 11 June 2018
Accepted Date: 24 June 2018
Please cite this article as: G. Singh, J. Singh, A. Singh, J. Singh, M. Kumar, K. Gupta, S. Chhibber,
Synthesis, characterization and antibacterial studies of schiff based 1,2,3-triazole bridged silatranes,
Journal of Organometallic Chemistry (2018), doi: 10.1016/j.jorganchem.2018.06.024.
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ACCEPTED MANUSCRIPT
Synthesis, characterization and antibacterial studies of schiff based 1,2,3-
triazole bridged silatranes
Gurjaspreet Singha*, Jasbhinder Singha, Akshpreet Singha, Jandeep Singhb, Manoj
Kumara, Kshitiz Guptac, Sanjay Chhibberc,
a Department of Chemistry and Centre of Advanced Studies, Panjab University, Chandigarh
160014, India.
b Lovely Professional University, Phagwara, India.
c Department of Microbiology, Panjab University, Chandigarh 160014, India.
* Corresponding author
Dr. Gurjaspreet Singh
Associate Professor
Department of Chemistry and Centre of Advanced Studies
Panjab University, Chandigarh, India
Email: gjpsingh@pu.ac.in
Abstract
A single step Cu (I) assisted click silylation reaction had been used for the synthesis of novel
Schiff based 1,2,3-triazole bridged silatrane (SBTBS)-scaffolds (5a-5f) using
polyfunctionalised Schiff based 1,2,3-triazole bridged organotriethoxysilanes (SBTBOTS)
(4a-4f) as precursors. These compounds were synthesized in excellent yields using an
economical, simple and biocompatible synthetic procedure and their structures were
characterized by various spectroscopy methods such as IR, NMR (1H and 13C) and
elemental analysis. The presence of different pharmacologically active segments into a single

ACCEPTED MANUSCRIPT
triazole unit can result into impressive achievement in their bioactivity. So, antibacterial
studies of the silatranes (5a-5f) were also carried out and it was observed that all the
compounds showed potential antibacterial activity. The results also indicate that activity of
compound 5f is even comparable to the standard drug, cefepime.
Keywords:
Antibacterial
Click silylation
Silatrane
Trialkoxysilane
Triazole
1. Introduction
Silatranes, with general formula X_Si(OCH2CH2)3N, are intramolecular complex of silicon
with triethanolamine ligand, exhibiting exclusive structure [1,2]. The unconventional trigonal
bipyramidal framework of silatranes route to their high electronegativity and high dipole
moment which sanction the chemisorption of these entities on the surface of cellular
membranes via hydrogen interactions with equatorial oxygen atoms or by dipole-dipole
interactions [3-5]. Being the atrane molecules, a feature of interest in these compounds is
transannular dative bonding interaction between the silicon and the nitrogen atom which
furnish some peculiar chemical properties [6]. The length of N→Si dative bond depends on
electronegativity of the substituent on the silicon atom [7]. Silatranes discover multitudinous
prominence advantages in catalysis, biomaterials, sol-gel, nano chemistry, agriculture,
medicine and pharmacology [8].
Schiff bases, also referred as Imines, have drawn attention of scientists owing to their easy
synthesis and ease of metal complexation [9]. 2-Hydroxy-1-naphthaldehyde in literature is
illustrated as versatile fluorescent chemosensor building block towards a gob of cations,
anions and many organic moieties. So via hybridization with primary amines and 1, 2, 3,

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triazole bridged silatranyl (TBS) group, the molecule can be used as coherent fluorophore
unit for a variety of analytes [10,11] as presented in Fig. 1.
Fig. 1: Schematic representation of Schiff based 1,2,3- triazole linked silatrane as fluorescent
chemosensor
The substantial, high reliability, excellent efficiency (nearly 100% yield) and fastidious
reaction is the paradigm of a click procedure. Inevitably, this protocol has explored
tremendously increasing application in an array of disciplines such as drug discovery and
medicinal chemistry, bio-conjugation, polymer, organic chemistry, catalysts and materials
science [12-15]. The pioneer effort by Cattoen and co-workers encouraged us to develop a
hybrid key intermediate 1, 2, 3-triazole bridged oragnotriethoxysilanes (TBOTES) via ‘Click
Silylation’ [16,17]. The label “Click Silylation” enclosed the powerful master plan of click
and organosilicon chemistry that offer covalent congregation of smaller fragments (terminal
alkynes and azide function) to TBOTES-linkers, which can further perform as an ancestral
forefather for the development of efficient variegated silatranes [18,19].
Herein, we report a riveting application of click reaction in organosilicon chemistry to
fabricate a library of well defined Schiff based 1,2,3-triazole bridged silatrane (SBTBS)-
scaffolds, that can offer an army of imperative advantages over organotriethoxysilanes
(OTS). Unlike OTS-linkers, assembled SBTBS-scaffolds are stable towards hydrolysis,
oxidation and reduction and the ability of the N (3) atom of the 1,2,3-triazole, O (3) atom of
the silatrane ring and N (1) atom of Schiff base segment to act as a hydrogen bond acceptor
can make it an outstanding fragment in supramolecular chemistry. Further, schiff bases,
1,2,3-triazole compounds and silatranes are individually known for their antibacterial
activity. Conjugation of these three potent anti-bacterial agents can have synergic effects on
their individual potentials and hence the synthesized SBTBS compounds (5a-5f) were also

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monitored against bacterial survival i.e. for their antibacterial activity against P. aeruginosa
PAO1, Klebsiella pneumoniae 43816, S. epidermidis 3382 and S. aureus MRSA.
2. Experimental
2.1. Materials and methods
All the syntheses were carried out under inert dry nitrogen atmosphere using vacuum glass
line. The organic solvents were dried according to standard procedures [20]. 2-Hydroxy-1-
naphthaldehyde (Aldrich), Aniline (Qualigens, >99%), naphthalen-1-amine (Aldrich), 4-
(phenyldiazenyl)benzenamine (CDH), 4-chlorobenzenamine (Aldrich), 4-nitrobenzenamine
(Aldrich), 4-fluorobenzenamine (SDFCL), 2-methoxybenzenamine (SDFCL), propargyl
bromide (80% in toluene) (Aldrich), potassium carbonate (Thomas), sodium sulphate (Finar),
Bromotris (triphenylphosphine) copper(I) [CuBr(PPh3)3] (Aldrich), tetrahydrofuran (THF)
(CDH), Triethylamine (Et3N) (SDFCL), triethanolamine (CDH), KOH (CDH), Toluene
(SDFCL), DMF (FINAR) were used as received. 3-azidopropyltriethoxysilane (AzPTES)
was synthesized by known procedure from literature [21,22]. Infrared spectrum was obtained
neat on a Thermo Scientific Fischer spectrometer. Elemental analysis was carried out on
Perkin Elmer Model 2400 CHNS elemental analyzer and Thermo Scientific Flash 2000
13
organic elemental analyzer. Multinuclear NMR (1H, C) spectra were recorded on a Bruker
advance II 400 and on a Jeol (AL 300 MHz) spectrometer using CDCl3 as internal reference
and chemical shifts were reported relative to tetramethylsilane. Melting points were
uncorrected and measured in a Mel Temp II device using sealed capillaries. Mass analysis
was performed on a WATERS, Q-TOF micro MASS spectrometer (ESI source with capillary
voltage, 3000 V). Theoretical studies were done using density functional theory (DFT)
calculations with hybrid density functional (B3LYP)/6-31+G(d) basis set level of theory.
2.2. General procedure for synthesis of schiff based alkynes (SBA) (3a-3f):- 2-(prop-2-
ynyloxy)-1-naphthaldehyde (1) was synthesised as described in the literature from 2-
hydroxy-1-naphthaldehyde [23]. Then amine (2.3 mmol) (2a-2f) was added to an ethanolic
solution of 1 (0.5g, 2.3mmol) in a single neck round bottom flask and refluxed for 4 h
followed by cooling to room temperature. The solid product was filtered and dried to obtain
the yellow colored schiff bases alkynes (3a-3f).

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2.3. General procedure for synthesis of Schiff based 1, 2, 3-triazole bridged
organotriethoxysilanes (SBTBOTS)-scaffolds (4a-4f):- Under dry nitrogen atmosphere using
vacuum glass line, Schiff based alkynes (1 equiv) were blended to 1:1 THF/Et3N solvent
mixture taken in a 2-neck round bottomed flask and the whole composition was mixed for 20
min at room temperature. Slow dropwise addition of AzPTES (1 equiv/alkyne function) was
done followed by catalyst [CuBr(PPh3)3] (0.01 mmol/alkyne function) loading. The mixture
was refluxed at 60 for 5h. The reaction was then escort to room temperature. The solvents
were evaporated under reduced pressure followed by the addition of n-pentane. The reaction
mixture was then filtered and quantity of filterate under reduced pressure furnished the
viscous pale yellow SBTBOTS (4a-4f) in fantastic yield.
2.3.1.
Synthesis
of
(Z)-N-((2-((1-(3-(triethoxysilyl)propyl)-1H-1,2,3-triazol-4-
yl)methoxy)naphthalen-1-yl)methylene)benzenamine (4a):
The quantities used were: 3a (0.42 g, 1.47 mmol), AzPTES (0.37 g, 1.47 mmol), Yield 96%;
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.43 (t, 2H, J = 5.8 Hz, ─SiCH2─), 1.09 (t, J =
7.3 Hz, 9H, ─OCCH3), 1.76 (m, 2H, ─CCH2C), 3.67 (m, 6H, ─OCH2C), 4.20 (t, J = 7.6 Hz,
2H, ─NCH2CC─), 5.35 (s, 2H, ─OCH2Tz), 7.12– 7.81 (m, 11H), 9.13 (s, 2H, ─CH═N), 9.45
(d, J = 6.6 Hz, 1H, Naphthalene H). 13C NMR (400 MHz, CDCl3, 25 °C, δ, ppm): 7.6
(SiCH2), 18.4 (OCH2CH3), 24.1 (CCH2C), 53.8 (N3CH2), 58.4 (OCH2C), 63.6 (OCH2),
114.2─ 133.7 (Ar-C), 158.4 (CH═N).
2.3.2.
Synthesis
of
(Z)-N-((2-((1-(3-(triethoxysilyl)propyl)-1H-1,2,3-triazol-4-
yl)methoxy)naphthalen-1-yl)methylene)naphthalen-1-amine (4b):
The quantities used were: 3b (0.35 g, 1.00 mmol), AzPTES (0.26 g, 1.00 mmol), Yield 93%;
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.41 (t, 2H, J = 8 Hz, ─SiCH2─), 1.07 (t, J = 7.4
Hz, 9H, ─OCCH3), 1.83 (m, 2H, ─CCH2C), 3.67 (m, 6H, ─OCH2C), 4.20 (t, J = 6.7 Hz, 2H,
─NCH2CC─), 5.37 (s, 2H, ─OCH2Tz), 6.96 – 7.87 (m, 13H), 9.27 (s, 2H, ─CH═N), 9.68 (d,
J = 11.6 Hz, 1H-Naphthalene H). 13C NMR (400 MHz, CDCl3, 25 °C, δ, ppm): 7.4 (SiCH2),
18.6 (OCH2CH3), 22.6 (CCH2C), 52.5 (N3CH2), 58.3 (OCH2C), 63.7 (OCH2), 112.9 ─ 134.0
(Ar-C), 158.5 (CH═N).
2.3.3. Synthesis of (Z)-4-((E)-phenyldiazenyl)-N-((2-((1-(3-(triethoxysilyl)propyl)-1H-1,2,3-
triazol-4-yl)methoxy)naphthalen-1-yl)methylene)benzenamine (4c):
The quantities used were: 3c (0.67 g, 1.70 mmol), AzPTES (0.42 g, 1.70 mmol), Yield 97%;

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1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.48 (t, 2H, J = 11 Hz, ─SiCH2─), 1.17 (t, J =
9.0 Hz, 9H, ─OCCH3), 1.95 (m, 2H, ─CCH2C), 3.70 (m, 6H, ─OCH2C), 4.20 (t, J = 7.20
Hz, 2H, ─NCH2CC─), 5.22 (s, 2H, ─OCH2Tz), 7.13 – 7.53 (m, 16H), 9.25 (s, 2H, ─CH═N),
13
9.42 (d, J = 3.3 Hz, 1H-Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ, ppm): 8.4
(SiCH2), 18.2 (OCH2CH3), 24.1 (CCH2C), 52.5 (N3CH2), 58.4 (OCH2C), 66.1 (OCH2), 113.5
─ 137.8 (Ar-C), 158.8 (CH═N).
2.3.4. Synthesis of (Z)-4-nitro-N-((2-((1-(3-(triethoxysilyl)propyl)-1H-1,2,3-triazol-4-
yl)methoxy)naphthalen-1-yl)methylene)benzenamine (4d):
The quantities used were: 3d (0.54 g, 1.63 mmol), AzPTES (0.40 g, 1.63 mmol), Yield 98%;
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.44 (t, 2H, J = 7.5 Hz, ─SiCH2─), 1.12 (t, J =
3.6 Hz, 9H, ─OCCH3), 1.76 (m, 2H, ─CCH2C), 3.66 (m, 6H, ─OCH2C), 4.24 (t, J = 6.90
Hz, 2H, ─NCH2CC─), 5.36 (s, 2H, ─OCH2Tz), 7.11 – 8.18 (m, 10H), 9.14 (s, 2H, ─CH═N),
13
9.44 (d, J = 8.7 Hz, 1H-Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ, ppm): 6.4
(SiCH2), 17.2 (OCH2CH3), 23.1 (CCH2C), 51.5 (N3CH2), 57.4 (OCH2C), 62.4 (OCH2), 113.1
─ 134.1 (Ar-C), 158.3 (CH═N).
2.3.5. Synthesis of (Z)-4-fluoro-N-((2-((1-(3-(triethoxysilyl)propyl)-1H-1,2,3-triazol-4-
yl)methoxy)naphthalen-1-yl)methylene)benzenamine (4e):
The quantities used were: 3e (0.50 g, 1.65 mmol), AzPTES (0.41 g, 1.65 mmol), Yield 95%;
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.58 (t, 2H, J = 7.5 Hz, ─SiCH2─), 1.09 (t, J =
6.9 Hz, 9H, ─OCCH3), 1.82 (m, 2H, ─CCH2C), 3.75 (m, 6H, ─OCH2C), 4.21 (t, J = 9.5 Hz,
2H, ─NCH2CC─), 5.36 (s, 2H, ─OCH2Tz), 7.24 – 7.87 (m, 10H), 9.23 (s, 2H, ─CH═N),
13
9.48 (d, J = 8.1 Hz, 1H-Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ, ppm): 8.4
(SiCH2), 17.8 (OCH2CH3), 23.5 (CCH2C), 53.6 (N3CH2), 58.2 (OCH2C), 62.8 (OCH2), 123.1
─ 134.1 (Ar-C), 158.4 (CH═N).
2.3.6. Synthesis of (Z)-2-methoxy-N-((2-((1-(3-(triethoxysilyl)propyl)-1H-1,2,3-triazol-4-
yl)methoxy)naphthalen-1-yl)methylene)benzenamine (4f):
The quantities used were: 3f (0.50 g, 1.60 mmol), AzPTES (0.39 g, 1.60 mmol), Yield 94%.
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.27 (t, 2H, J = 7.5 Hz, ─SiCH2─), 1.26 (t, J =
4.8 Hz, 9H, ─OCCH3), 1.78 (m, 2H, ─CCH2C), 3.66 (m, 6H, ─OCH2C), 3.89 (s, 3H,
─ArOCH3), 4.23 (t, J = 6.3 Hz, 2H, ─NCH2CC─), 5.36 (s, 2H, ─OCH2Tz), 7.22 – 7.70 (m,
13
10H), 9.21 (s, 2H, ─CH═N), 9.48 (d, J = 8.1 Hz, 1H-Naphthalene H). C NMR (400 MHz,
CDCl3, 25 °C, δ, ppm): 7.4 (SiCH2), 18.2 (OCH2CH3), 24.6 (CCH2C), 51.0 (N3CH2), 57.5
(OCH2C), 62.8 (OCH2), 111.8 ─ 133.4 (Ar-C), 158.6 (CH═N).

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2.4. General procedure for synthesis of Schiff based 1, 2, 3-triazole bridged silatrane
(SBTBS)-scaffolds (5a-5g):- In the stirred solution of triethanolamine (1 equiv) in toluene (30
ml) taken in
a
round bottomed flask incorporated with
a
dean stark
equipment, SBTBOTS (1 equiv) was added drop wise followed by the addition of KOH in
the catalytic amount. The mixture was refluxed for 4 h in order to remove ethanol
azeotropically which was formed during the reaction. Then the solvent was removed under
reduced pressure followed by addition of 15 ml hexane. The content was stirred for 24 h after
which the products (5a-5f) segregated as yellow solid which were filtered under nitrogen
atmosphere and dried with the help of vacuum.
2.4.1. Synthesis of (Z)-N-((2-((1-(3-(2,8,9-trioxa-5-aza-1-sila-bicyclo[3.3.3]undecan-1-
yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-yl)methylene)benzenamine (5a):
The quantities used were: 4a (0.50 g, 0.9 mmol), triethanolamine (0.14 g, 0.9 mmol), Yield
89%; m. pt. 225-229 °C. Anal. Calcd for C29H33N5O4Si (%): C, 64.06; H, 6.12; N, 12.88.
Found (%): C, 64.13; H, 6.17; N, 12.78. IR (neat, cm−1): 571 (N → Si), 743, 1043 (Si─O),
1
959 (C─C), 1072, 1221 (O─CH2), 1356 (CH2─N), 1599 (C═N), 2884 (C═C─H). H NMR
(300 MHz, CDCl3, 25 °C, δ, ppm): 0.79 (t, 2H, J = 5.7 Hz, ─SiCH2─), 1.76 (m, 2H,
─CCH2C), 2.47 (t, J = 9.0 Hz, 6H, ─OCCH2N), 3.43 (t, 6H, J = 5.7 Hz, ─OCH2C), 4.34 (t, J
= 6.4 Hz, 2H, ─NCH2CC─), 5.27 (s, 2H, ─OCH2Tz), 7.06– 7.65 (m, 11H), 9.13 (s, 2H,
13
─CH═N), 9.45 (d, J = 6.6 Hz, 1H, Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ,
ppm): 8.4 (SiCH2), 22.6 (CCH2C), 52.4 (OCH2CH2N), 53.8 (N3CH2), 56.8 (OCH2C), 67.9
(OCH2), 121.0 ─ 133.7 (Ar-C), 158.4 (CH═N).
2.4.2. Synthesis of (Z)-N-((2-((1-(3-(2,8,9-trioxa-5-aza-1-sila-bicyclo[3.3.3]undecan-1-
yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-yl)methylene)naphthalen-1-amine
(5b):
The quantities used were: 4b (1.414 g, 2.4 mmol), triethanolamine (0.36 g, 0.9 mmol), Yield
96%; m. pt. 238-242 °C. Anal. Calcd for C33H35N5O4Si (%): C, 66.75; H, 5.94; N, 11.80.
Found (%): C, 66.77; H, 5.89; N, 11.68. IR (neat, cm−1): 581 (N → Si), 778, 1058 (Si─O),
1
929 (C─C), 1052, 1241 (O─CH2), 1356 (CH2─N), 1609 (C═N), 2794 (C═C─H). H NMR
(300 MHz, CDCl3, 25 °C, δ, ppm): 0.79 (t, 2H, J = 7.2 Hz, ─SiCH2─), 1.84 (m, 2H,
─CCH2C), 2.58 (t, J = 6.2 Hz, 6H, ─OCCH2N), 3.53 (t, 6H, J = 5.7 Hz, ─OCH2C), 4.19 (t, J
= 5.8 Hz, 2H, ─NCH2CC─), 5.38 (s, 2H, ─OCH2Tz), 7.69– 7.89 (m, 13H), 9.31 (s, 2H,
13
─CH═N), 9.73 (d, J = 8.4 Hz, 1H, Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ,

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ppm): 13.1 (SiCH2), 26.2 (CCH2C), 50.8 (OCH2CH2N), 53.3 (N3CH2), 57.4 (OCH2C), 63.8
(OCH2), 123.0 ─ 134.0 (Ar-C), 158.5 (CH═N).
2.4.3. Synthesis of
(Z)-4-((E)-phenyldiazenyl)-N-((2-((1-(3-(2,8,9-trioxa-5-aza-1-sila-
bicyclo[3.3.3]undecan-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-
yl)methylene)benzenamine (5c):
The quantities used were: 4c (1.00 g, 1.50 mmol), triethanolamine (0.23 g, 1.50 mmol), Yield
91%; m. pt. 232-235 °C. Anal. Calcd for C33H37N7O4Si (%): C, 64.89; H, 5.76; N, 15.14.
Found (%): C, 64.73; H, 5.77; N, 15.08. IR (neat, cm−1): 572 (N → Si), 789, 1056 (Si─O),
958 (C─C), 1053, 1261 (O─CH2), 1396 (CH2─N), 1625 (C═N), 2812 (C═C─H).
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.74 (t, 2H, J = 7.2 Hz, ─SiCH2─), 1.29 (m, 2H,
─CCH2C), 2.49 (t, J = 6.2 Hz, 6H, ─OCCH2N), 3.42 (t, 6H, J = 5.7 Hz, ─OCH2C), 4.16 (t, J
= 5.8 Hz, 2H, ─NCH2CC─), 5.24 (s, 2H, ─OCH2Tz), 6.95– 7.74 (m, 16H), 9.18 (s, 2H,
13
─CH═N), 9.58 (d, J = 8.4 Hz, 1H, Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ,
ppm): 8.2 (SiCH2), 21.8 (CCH2C), 53.8 (OCH2CH2N), 56.8 (N3CH2), 59.5 (OCH2C), 67.9
(OCH2), 121.0 ─ 133.7 (Ar-C), 158.4 (CH═N).
2.4.4. Synthesis of (Z)-N-((2-((1-(3-(2,8,9-trioxa-5-aza-1-sila-bicyclo[3.3.3]undecan-1-
yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-yl)methylene)-4-nitrobenzenamine
(5d):
The quantities used were: 4d (0.81 g, 1.40 mmol), triethanolamine (0.21 g, 1.40 mmol), Yield
95%; m. pt. 246-215 °C. Anal. Calcd for C29H32N6O6Si (%): C, 59.17; H, 5.48; N, 14.28.
Found (%): C, 59.12; H, 5.27; N, 14.09. IR (neat, cm−1): 559 (N → Si), 765, 1106 (Si─O),
978 (C─C), 1087, 1361 (O─CH2), 1348 (CH2─N), 1648 (C═N), 2858 (C═C─H).
1H NMR (300 MHz, CDCl3, 25 °C, δ, ppm): 0.79 (t, 2H, J = 5.1 Hz, ─SiCH2─), 1.80 (m, 2H,
─CCH2C), 2.48 (t, J = 4.8 Hz, 6H, ─OCCH2N), 3.43 (t, 6H, J = 4.5 Hz, ─OCH2C), 4.36 (t, J
= 6.2 Hz, 2H, ─NCH2CC─), 5.28 (s, 2H, ─OCH2Tz), 7.11– 7.81 (m, 10H), 9.28 (s, 2H,
13
─CH═N), 9.43 (d, J = 4.4 Hz, 1H, Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ,
ppm): 8.2 (SiCH2), 23.6 (CCH2C), 50.2 (OCH2CH2N), 52.4 (N3CH2), 56.6 (OCH2C), 59.5
(OCH2), 123.3 ─ 133.8 (Ar-C), 158.7 (CH═N).
2.4.5. Synthesis of
(Z)-N-((2-((1-(3-(2,8,9-trioxa-5-aza-1-sila-bicyclo[3.3.3]undecan-1-
yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-yl)methylene)-4-fluorobenzenamine
(5e):
The quantities used were: 4e (1.00 g, 1.81 mmol), triethanolamine (0.27 g, 1.81 mmol), Yield
98%; m. pt. 231-235 °C. Anal. Calcd for C29H32FN5O4Si (%): C, 62.01; H, 5.74; N, 12.47.
Found (%): C, 62.23; H, 5.57; N, 12.29. IR (neat, cm−1): 569 (N → Si), 768, 1096 (Si─O),

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1
998 (C─C), 1117, 1291 (O─CH2), 1356 (CH2─N), 1689 (C═N), 2815 (C═C─H). H NMR
(300 MHz, CDCl3, 25 °C, δ, ppm): 0.41 (t, 2H, J = 9.0 Hz, ─SiCH2─), 1.97 (m, 2H,
─CCH2C), 2.80 (t, J = 6.0 Hz, 6H, ─OCCH2N), 3.74 (t, 6H, J = 3.0 Hz, ─OCH2C), 4.33 (t, J
= 12.0 Hz, 2H, ─NCH2CC─), 5.13 (s, 2H, ─OCH2Tz), 7.13– 7.95 (m, 10H), 9.25 (s, 2H,
13
─CH═N), 9.51 (d, J = 4.4 Hz, 1H, Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ,
ppm): 13.2 (SiCH2), 26.3 (CCH2C), 50.9 (OCH2CH2N), 53.4 (N3CH2), 57.4 (OCH2C), 63.7
(OCH2), 122.4 ─ 133.9 (Ar-C), 158.4 (CH═N). Calcd for [M+H]+ 562.6; Found 562.1.
2.4.6. Synthesis of
(Z)-N-((2-((1-(3-(2,8,9-trioxa-5-aza-1-sila-bicyclo[3.3.3]undecan-1-
yl)propyl)-1H-1,2,3-triazol-4-yl)methoxy)naphthalen-1-yl)methylene)-2-methoxybenzenamine
(5f):
The quantities used were: 4f (1.00 g, 1.77 mmol), triethanolamine (0.27 g, 1.77 mmol), Yield
94%; m. pt. 239-244 °C. Anal. Calcd for C30H35N5O5Si (%): C, 62.80; H, 6.12; N, 12.21.
Found (%): C, 62.88; H, 5.99; N, 12.33. IR (neat, cm−1): 573 (N → Si), 786, 1065 (Si─O),
1
978 (C─C), 1079, 1298 (O─CH2), 1346 (CH2─N), 1676 (C═N), 2867 (C═C─H). H NMR
(300 MHz, CDCl3, 25 °C, δ, ppm): 0.58 (t, 2H, J = 7.7 Hz, ─SiCH2─), 1.84 (m, 2H,
─CCH2C), 2.53 (t, J = 6.9 Hz, 6H, ─OCCH2N), 3.473(t, 6H, J = 8.9 Hz, ─OCH2C), 4.36 (t, J
= 10.7 Hz, 2H, ─NCH2CC─), 5.43 (s, 2H, ─OCH2Tz), 7.26– 7.77 (m, 10H), 8.05 (s, 2H,
13
─CH═N), 9.22 (d, J = 8.7 Hz, 1H, Naphthalene H). C NMR (400 MHz, CDCl3, 25 °C, δ,
ppm): 7.5 (SiCH2), 23.6 (CCH2C), 52.5 (OCH2CH2N), 56.0 (N3CH2), 58.8 (OCH2C), 63.8
(OCH2), 122.9 ─ 133.4 (Ar-C), 157.8 (CH═N).
2.5. Biological studies
2.5.1. Antibacterial assay
All the six compounds (5a-5f) were screened for their antibacterial activity against P.
aeruginosa PAO1, Klebsiella pneumoniae 43816, S. epidermidis 3382 and S. aureus MRSA
by following the well plate assay [24]. The nutrient agar was poured in petri dish (100 mm
size and 4mm depth). The agar plates were then seeded with overnight broth culture, diluted
to 0.5 McFarland turbidity (~ 1.5. 108 cells/ml). Then agar was punched to make wells of
4mm depth and 3mm diameter. A 1 mg/ml solution of all the four bacteria was loaded in
separate wells and a zone of inhibition observed after overnight incubation at 37 .
2.5.2. Minimum inhibitory concentration

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For MIC assays, a stock solution of 1 mg/ml of each test compound was prepared in ethyl
acetate. Further the stock solution was serially diluted in the range of 1 mg/ml to 1.65 µg/ml.
Then test compounds at various concentrations were added to the nutrient broth in a 96 well
microtitre plate. The different bacterial strains at 108 bacterial cells/ml concentrations were
added to well in an assigned row. Then microtitre plate was incubated at 37 overnight and
examined for growth of the test organisms. The lowest concentration of the test compound
that cleared bacterial growth in a well of the microtitre plate was taken as MIC.
3. Results and discussion
3.1. Synthesis
2-hydroxy-1-naphthaldehyde was used as starting ingredient for the synthesis of SBTBOTS
(4a-4f) and SBTBS (5a- 5f) [Scheme 1, Table 1]. Firstly, 2-hydroxy-1-naphthaldehyde was
transformed into 2-(prop-2-ynyloxy)-1-naphthaldehyde (1) by the reaction with propargyl
bromide in DMF assisted by base K2CO3. Treatment of (1) with amines (2a-2f) gave Schiff
based alkynes SBA (3a-3f). These SBA (3a-3f) were then coupled with 3-AzPTES via
copper-catalyzed azide–alkyne cycloaddition reaction to form Schiff based 1, 2, 3-triazole
bridged triethoxysilanes (SBTBOTS - 4a-4f). This strategy is based on the tremendously
efficient CuBr(PPh3)3–THF–Et3N set-up. Finally, transesterification reaction of the
synthesized SBTBOTS with triethanolamine in toluene, catalysed by KOH yielded SBTBS
in good yields. These silatranes were observed to be hydrolytically more stable than their
corresponding triethoxysilane analogues.

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R
O
O
O
(B)
H2N
2a-2f
N
O
(A)
R
OH
1
3a-3f
(C)
R
R
N
N
O
O
Si
(D)
N
O
O
O
N
N
O
N
Si
O
N
N
N
O
5a-5f
4a-4f
Scheme 1. (A) Propargyl bromide, K2CO3, DMF, 24h (B) amine 2a-2f, ethanol, reflux, 4h,
(C) AzPTES, Cu(PPh3)3Br, Et3N, THF, 5h, 60oC (D) Triethanolamine, KOH, toluene, 6h.

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Table 1: Synthesised schiff based terminal alkynes (3a-3f) organotrialkoxysilanes (4a-4f) and silatranes (5a-5f).
Substrate amines
(2a–2f)
(SBA)
(SBTBOTS)
(SBTBS)
(3a–3f)
(4a–4f)/ Yield
(5a–5f)/ Yield/ M.Pt. (℃)
N
NH2
O
O
O
O
N
N
N
O
O
O
2a
N
N
N
O
N
O
N
N
9
5-22
/ 22
/ 94%
%
/ 99
5a
3a
4a/ 96%
O
N
O
N
O
O
O
O
N
NH2
N
N
N
O
N
O
N
N
O
4b/ 93%
N
2b
5b/ 96%/ 238-242
3b/ 95%
N
N
N
N
N
O
O
O
O
N
N
N
O
N
N
O
N
N
O
N
O
O
N
N
N
N
N
NH2
5c/ 91%/ 232-235
4c/ 97%
3c/ 97%
2c

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O2N
O2N
O
O
O
O
N
N
N
N
O2N
NH2
O
O
N
O
N
O
O2N
O
N
N
N
N
2d
4d/ 98%
5d 95%/ 246-251
F
3d 98%
F
O
O
N
O
O
N
F
NH2
S
i
N
N
O
N
N
N
O
O
N
N
O
2e
F
O
N
4e/ 95%
5
-23
231
%/
98
5e/
OMe
3e/ 99%
OMe
N
OMe
O
O
N
NH2
OMe
N
N
O
O
O
N
N
O
O
N
O
O
N
N
2f
N
4f/ 94%
5f/ 94%/ 239-244
3f/ 95%

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3.2. NMR spectroscopy
1H NMR spectra of SBTBS (5a- 5f) on enthusiastic observation revealed almost similar
vogue in signals as sketched in NMR study of SBTBOTS (4a-4f). All the silatranes (5a-5f)
manifested a set of multiplets due to –CH2 unit of propyl chain in the range of δ 1.99 – 1.78
ppm. The –OCH2 clamped to 1, 2, 3-triazole heterocycle was extremely de-shielded which
appeared at δ 5.40–5.22 ppm. The aromatic ring protons conjugated with Schiff base segment
were signalled as multiplets in the region δ 8.21–7.11 ppm. The Schiff base proton ─CH═N
appeared in the range of δ 9.25-9.15 ppm. The aromatic protons of Naphthalene ring
signalled at δ 9.68 – 9.545 ppm. Moreover, -OCH2CN protons of atrane ring appeared as
triplet in the region δ 3.85–3.65 ppm. The NMR spectra of silatrane varied from silane by the
complete disappearance of a quartet and triplet at δ 3.85–3.65 ppm and δ 1.21–1.10 ppm and
origination of two new triplets with δ 3.76–3.42 due to –NCH2CH2O– and at δ 2.80– 2.61 due
to –NCH2CH2O– arms of atrane ring. One more crucial shift in NMR was noticed for
methylene proton of –CH2Si in which peak switched from the maximum of δ 0.72 ppm to the
minimum range of δ 0.35 ppm. Any other extra effect due to attachment of distinct moieties
at ─CH═N site was negligible on other aromatic protons. In 13C NMR spectra, the
considerable shift was observed due to –N3C– of 1, 2, 3-triazole as it fetched from δ 60.1–
52.3 ppm to of δ 131.2–127.8 ppm. The methylene carbon of propyl chain associated to
silicon atom –C–Si– materialized as the most shielded carbon atom at around δ 7.4 ppm for
triethoxysilanes 4a–4f which was displaced from δ 10–7 ppm to δ 17.3–9.5 ppm for
compounds 5a–5f designated prompting of hypervalency at silicon center. For silatranes, the
–OCCN– of atrane cage framework appeared in the range δ 62.1–52.5 ppm while –OCCN–
appeared at δ 51.6–46.8 ppm.
3.3. IR spectroscopy
The neat vibrational spectroscopic statistics for all compounds was recorded in the region
4000–400 cm-1. All the resulting frequencies in terms of IR spectra were in fulfilment with
the awaited structure of synthesized compounds. The complete clear region in the range
2180–2065 cm-1 authenticate complete cyclization of AzPTES and SBA (3a–3f) to 1, 2, 3-
triazole bridged triethoxysilanes (4a–4f). There were keen absorption bands in the region

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3025–2799 cm-1 and 1670–1456 cm-1 that congruous to aromatic conjugation in Schiff base
substituents and 1,2,3-triazole ring. The transannular bond N–Si in the silatranes 5a–5f was
signalled by the absorption bands in the region 752–525 cm-1. The –CH vibrations in FTIR
spectra of all triethoxysilanes 4a–4f were depicted near 2990–2715 cm-1. The CH═N
segment gave sharp peak at 1648 cm-1.
3.4. Biological studies
All the compounds (5a-5f) were screened for their antibacterial activity against gram positive
and gram negative bacteria by well plate assay (Table 2). Interestingly, all of them were
found positive for their activity against K. pneumoniae B5O55, P. aeruginosa PAO1, S.
aureus MRSA and S. epidermidis 3382 viewed as clear zones on nutrient agar plates.
Table 2. Antibacterial activity of Schiff based 1, 2, 3-triazole linked silatranes
Bacterial agent
MIC (µg/ml)
16.5 ± 1.66
16.5 ± 2.12
3.25 ± 0.053
3.25 ± 0.027
625 ± 26.5
625 ± 53
312 ± 13.25
312 ± 26.5
106 ± 3.32
106 ± 6.75
53 ± 3.32
Compound
K. pneumoniae 43816
P. aeruginosa PAO1
S. aureus MRSA
CEFEPIME
S. epidermidis 3382
K. pneumoniae 43816
P. aeruginosa PAO1
S. aureus MRSA
CONTROL
S. epidermidis 3382
K. pneumoniae 43816
P. aeruginosa PAO1
S. aureus MRSA
5a
5b
5c
5f
S. epidermidis 3382
K. pneumoniae43816
P. aeruginosa PAO1
S. aureus MRSA
53 ± 6.75
312 ± 13.25
106 ± 6.75
53 ± 3.32
53 ± 3.32s
106 ± 6.75
106 ± 13.50
26.5 ± 3.32
53 ± 6.75
106 ± 12.50
106 ± 6.75
26.5± 1.66
26.5± 3.32
26.5± 1.66
26.5± 1.66
13.25± 1.66
13.25± 3.32
S. epidermidis 3382
K. pneumoniae 43816
P. aeruginosa PAO1
S. aureus MRSA
S. epidermidis 3382
K. pneumoniae 43816
P. aeruginosa PAO1
S. aureus MRSA
S. epidermidis 3382
K. pneumoniae43816
P. aeruginosa PAO1
S. aureus MRSA
5d
S. epidermidis 3382

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K. pneumoniae 43816
P. aeruginosa PAO1
S. aureus MRSA
26.5± 3.32
13.25± 0.83
3.25± 0.41
3.25± 0.83
5e
S. epidermidis 3382
The minimum inhibitory concentration of these compounds was determined by following the
method given by Balouiri et al [25]. The MIC of these compounds was compared to that of
cefepime which is a drug of choice against gram positive as well as gram negative bacteria.
By virtue of the presence of an outer membrane, Gram negative bacteria are generally more
resistant towards a particular antibiotic than their Gram positive cousins [26]. Hence, all
chemical compounds were found to be more effective against gram positive bacteria as
compared to their gram negative cousins. For gram negative bacteria, 5d and 5f were seen as
the drugs of choice with MIC of 26.5µg/ml and 26.5 µg/ml against K. pneumoniae B5O55
respectively and MIC of 26.5µg/ml and 13.25µg/ml against P. aeruginosa PAO1
respectively. Interestingly 5f was highly active against S. aureus MRSA and S. epidermidis
4432 with an MIC of 3.25µg/ml each respectively. The high activity of 5f can be due to the
presence of electron donating methoxy group. Hence the activity of 5f was comparable to the
activity of cefepime and could be considered a highly potent antibacterial compound for
future however, it’s in vitro cell cytotoxicity and in vivo activity will determine its future use.
3.5. Theoretical studies
The structure of Schiff based 1, 2, 3-triazole linked silatrane 5a was optimized using DFT
calculations by employing B3LYP/6-31+G(d) level of theory. The optimized structure and its
HOMO and LUMO orbitals are showm in figure 2.

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Figure 2. (a) Optimized structure of 5a along with its (b) HOMO and (c) LUMO orbitals
4. Conclusions
2-hydroxy-1-naphthaldehyde derived SBA and organosilicon compounds were productively
manufactured using an exclusive copper-catalyzed click approach. The resulting
organosilatranes were characterized by IR spectroscopy, NMR (1H and 13C) spectroscopy,
and elemental analysis. The synthesized compounds were applied for their use as
antibacterial agents against gram positive and gram negative bacteria. The results showed that
all the compounds showed significant activity but they were more effective against gram
positive bacteria as compared to their gram negative counterparts. Also it was observed that
the activity of compound 5f was even comparable to the drug in use.
Acknowledgments

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The authors would like to thank UGC, DST-PURSE and DST-SERB for providing financial
assistance for this study.
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Research Highlights
•
Schiff based 1,2,3-triazole bridged organotriethoxysilanes (SBTBOTS) and Schiff
based 1,2,3-triazole bridged silatrane (SBTBS) have synthesized.
The synthesis has been done using Cu (I) assisted click silylation reaction.
The synthesized silatranes were evaluated for their antibacterial activity against gram
positive and gram negative bacteria
•
•