Siloxane derivatives of 2-mercaptobenzothiazole

Article abstract of DOI:10.1016/j.mencom.2017.07.010

First organosilicon captax derivatives were obtained from 2-mercaptobenzothiazole and 1-(iodomethyl)-1,1,3,3,3-pentamethyl-or 1,3-bis(iodomethyl)-1,1,3,3-tetramethyldisiloxanes in the absence or in the presence of bases.

Full text of DOI:10.1016/j.mencom.2017.07.010

Mendeleev
Communications
Mendeleev Commun., 2017, 27, 352–354
Siloxane derivatives of 2-mercaptobenzothiazole
Larisa V. Zhilitskaya,* Nina O. Yarosh, Lyudmila G. Shagun, Ivan A. Dorofeev and Lyudmila I. Larina
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk,
Russian Federation. Fax: +7 3952 419 346; e-mail: lara_zhilitskaya@irioch.irk.ru
DOI: 10.1016/j.mencom.2017.07.009
Me
O
I
Si
S
Si
First organosilicon captax derivatives were obtained from
2-mercaptobenzothiazole and 1-(iodomethyl)-1,1,3,3,3-penta-
methyl- or 1,3-bis(iodomethyl)-1,1,3,3-tetramethyldisiloxanes
in the absence or in the presence of bases.
Me
SH
Me
Si
S
Me Me
Me
N
S
O
150 °C
– HI
N
H
Me
I–
O
2
I
I
Si
Si
Me
Me Me
Me
2-Mercaptobenzothiazole (captax) 1 and its derivatives are
biologically active compounds possessing antibacterial, fungicide,
anticonvulsive, anti-inflammatory, antitumor, antioxidant and
antiallergic properties.1 In industry, captax is employed as inhibitor
of metal corrosion, vulcanization accelerator,2 and promising lumi-
nescent material.3 Therefore, the investigations in this field may
result in discovery of novel unexpected properties and application
areas of such compounds. We assumed that introduction of the tetra-
methylsiloxane groups into a molecule of industrial 2-mercapto-
benzothiazole should impart elasticity, strength, chemical inert-
ness and biocompatibility to the products.4
The classical method for derivatization of 2-mercaptobenzo-
thiazole involves alkylation with haloalkanes in the presence
of bases1,5 (KOH, K2CO3, NaOMe, C5H5N) in water, ethanol,
acetone, sometimes on using ultrasound6 or microwave irra-
diation.7 The reaction with acyl chlorides affords a mixture of
N- and S-acylated products.8 Alkylation of S-alkylated 2-mercapto-
benzothiazoles with iodoalkane bearing the same alkyl group
proceeds across the nitrogen atom to deliver S,N-dialkylated
salt.9 The data on alkylation of 2-mercaptobenzothiazole with
iodomethyl derivatives of siloxane are lacking in the literature.
Meanwhile, the employment of these compounds in the reaction
with captax can provide a series of novel functionalized benzo-
thiazoles.
In this work, we have implemented the reaction of 2-mercapto-
enzothiazole 1 with mono- and bifunctional electrophilic reagents,
1-(iodomethyl)-1,1,3,3,3-pentamethyl- and 1,3-bis(iodomethyl)-
1,1,3,3-tetramethyldisiloxanes, in various media.
b
We expected that solvent- and base-free alkylation of 1 with
1-(iodomethyl)-1,1,3,3,3-pentamethyldisiloxane 2 on heating
would furnish S,N-dialkylation products, which under these con-
ditions could form cyclic polyiodides in one preparative step10,11
owing to the presence of labile iodomethyl moiety and flexible
siloxane bond in the molecule of the alkylating agent. Contrary
to these expectations, this reaction at 150°C proceeds selectively
(1H, 13C, 15N NMR monitoring) at the mercapto group to give bis-
salt 3 in 48% yield (Scheme 1).†
The key step of the reaction is the cleavage of siloxane bond12
in adduct 4 under the action of hydrogen iodide, which is released
†
IR spectra were recorded on aVertex 70 Bruker instrument for KBr pellets
(compounds 3, 6) and for thin film samples (4). 1H, 13C, 29Si, and 15N NMR
spectra were measured on Bruker DPX-400 and Bruker AV-400 at
400.13, 100.61, 161.98, and 40.56 MHz, respectively. Chemical shifts are
given relative to TMS (1H, 13C, 29Si) and MeNO2 (15N). 2D 1H-15N NMR
spectra were recorded using HMBC-gp 1H–15N correlation technique. The
elemental composition was determined on a Thermo Scientific Flash 2000
automatic CHNS-analyzer. The iodine content was determined by mercuri-
metric titration, silicon was determined by dry combustion method. Melting
points were determined on a Micro-Hot-Stage PolyTherm A apparatus.
The reaction course and the compounds purity were monitored by TLC
(Silufol UV-254 plates, acetone as an eluent).
Me
O
S
I
Si
Si
+
SH
Me
150 °C
– HI
Reaction of compound 1 with 2 or 5 (general procedure). A mixture of
2-mercaptobenzothiazole 1 (0.2 g, 1.2 mmol) and iodomethyldisiloxane
2 (0.35 g, 1.2 mmol) or 5 (0.25 g, 0.6 mmol) was stirred at 150°C for
3 h until the consumption of iodide (1H, 13C NMR monitoring), and
then cooled to room temperature. Then acetone (15 ml) was added, the
precipitate of salt 3 was filtered off, washed with acetone and diethyl
ether, and dried in vacuum.
N
Me Me Me
2
1
S
Me
O
HI
S
Si
– Me3SiOH
– Me3SiI
Si
Me
N
Me Me Me
4
2-{[3-(1,3-Benzothiazol-2-ylsulfanyl)methyl]-1,1,3,3-tetramethyl-
disiloxanylmethyl}sulfanyl-1,3-benzothiazole dihydroiodide 3. Yield
0.43 g (48%, from 2), 0.36 g (81%, from 5), white powder, mp 146–148°C.
IR (KBr, n/cm–1): 1076 (Si–O–Si). 1H NMR (DMSO-d6) d: 0.18 (s, 12H,
S
S
OH
+
I
S
S
Si
Si
N
N
3
Me), 2.66 (s, 4H, CH2S), 7.30 (dd, H4, JHH 8.2, 8.6 Hz), 7.41 (dd, H8,
Me Me
Me Me
3
3
3JHH 8.4, 8.6 Hz), 7.76 (d, H9, JHH 8.4 Hz), 7.89 (d, H4, JHH 8.2 Hz),
9.70 (br.s, 1H, NH). 13C NMR (DMSO-d6) d: 0.08 (Me), 19.17 (CH2),
121.56 (C4), 124.05 (C5,6), 126.19 (C7), 134.58 (C8), 152.85 (C9), 169.38
(SC). 15N NMR (DMSO-d6) d: –105.9. 29Si NMR (DMSO-d6) d: 5.2.
Found (%): C, 32.06; H, 3.30; I, 33.84; N, 3.56; S, 16.95; Si, 8.34. Calc.
for C20H26I2N2OS4Si2 (%): C, 32.08; H, 3.50; I, 33.90; N, 3.74; S, 17.13;
Si, 7.50.
S
S
O
Si
Si
S
S
– (Me3Si)2O
N
N
I–
I–
Me Me Me Me
H
H
3
Scheme 1
© 2017 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 352 –

Mendeleev Commun., 2017, 27, 352–354
in situ. This likely leads to intermediates (see Scheme 1) giving
mercapto group involving both iodomethyl fragments of siloxane 5
to produce compound 3 in 81% yield (1H, 13C, 15N NMR data).
The 29Si NMR spectrum of the reaction mixture contains, apart
from a signal of the silicon atom at 5.2 ppm (SCH2SiMe2), a
small signal in the region of 7.0 ppm assigned to (Me3Si)2O,
which is apparently formed upon partial reduction of two iodo-
methyl groups of the initial disiloxane 5.
finally bis-salt 3 and hexamethyldisiloxane. The latter can also
be formed via condensation of trimethylsilanol or reduction of
the iodomethyl function of siloxane 2 with hydrogen iodide
(Scheme 2). Formation of intermediate 4 (see Scheme 1) and
hexamethyldisiloxane is confirmed by the signals of silicon
atoms at 9.4, 3.3 and 7.0 ppm [typical of OSiMe3, SCH2SiMe2
and (Me3Si)2O] in the 29Si NMR spectra of the reaction mixture.
O
I
I
+
Si
1
3
2
Si
2 Me3SiOH
2
+ HI
150 °C
– 2 HI
– H2O
– I2
Me Me Me Me
Me3SiOSiMe3
– HI
5
– HI
Me3SiI + H2O
SiOH + Me SiI
3
Me3
5 + HI
Me3SiOSiMe3
Scheme 4
Scheme 2
The reaction of 2-mercaptobenzothiazole 1 with monoiodide 2
under classical conditions, which exclude formation of hydrogen
iodide and cleavage of the Si–O bond, affords hitherto unknown
siloxane sulfide 4 in 87% yield (Scheme 3).‡
When this reaction is carried out in acetone solution in the
presence of K2CO3, non-salt adduct 6 is formed in 90% yield
(Scheme 5).‡
S
Me
S
S
K2CO3
– KI
O
O
K2CO3
– 2 KI
S
1 + 2
Si
Si
S
S
2 1 + 5
Si
Si
Me
N
N
N
Me Me Me Me
Me Me
Me
4
6
Scheme 3
Scheme 5
Earlier10 we have shown that compound 2 under the action
of hydrogen iodide easily disproportionates to bis(iodomethyl)-
1,1,3,3-tetramethyldisiloxane 5 and (Me3Si)2O. Therefore, it is
not improbable that diiodide 5 can act as alkylating agent in
the base-free reaction of thiol 1 similarly to monoiodide 2. We
assumed that bis-salt 3 could be synthesized by alkylation of
2-mercaptobenzothiazole with bifunctional electrophile 5 in a
higher yield due to decrease of the losses related to cleavage of
the Si–O bond (Scheme 4).† In fact, the reaction proceeds at the
It is known that the reaction of S-alkylated 2-mercapto-
benzothiazoles with iodoalkanes proceeds at the nitrogen atom
for 50 h to deliver S,N-dialkylated salt.9 We also attempted to
synthesize analogous dialkylated salt from reactants 2 and 4
1
(solvent-free, 150°C, 6 h). According to the H NMR data, the
ratio of this product to the starting compound 4 was 1:1. In the
1H NMR spectrum, a proton signal appeared at 4.13 ppm, while in
2D 1H–15N HMBC NMR spectrum, a cross-peak (–205.5 ppm)
between nitrogen atom and CH2 group protons was observed (for
3 this value corresponds to –105.9 ppm). Optimization of the
conditions should increase preparative yield of the target product.
In conclusion, alkylation of 2-mercaptobenzothiazole with
1-(iodomethyl)-1,1,3,3,3-pentamethyl- and 1,3-bis(iodomethyl)-
1,1,3,3-tetramethyldisiloxanes both in the absence and presence of
the bases selectively occurs at the mercapto group to furnish first
siloxane derivatives of captax. Base-free reaction of 2-mercapto-
benzothiazole with 1-(iodomethyl)-1,1,3,3,3-pentamethylsiloxane
is accompanied by cleavage of the Si–O bond in S-alkylation
adduct with the subsequent condensation of the silanols and
iodosilanes thus formed.
‡
Reaction of 1 with 2 or 5 in the presence of K2CO3 (general procedure).
1 n aqueous solution of K2CO3 (pH 8) was added to a solution of
2-mercaptobenzothiazole 1 (0.2 g, 1.2 mmol) in acetone (20 ml). Then
a solution of iodomethyldisiloxane 2 (0.35 g, 1.2 mmol) or 5 (0.25 g,
0.6 mmol) in acetone (5 ml) was added dropwise, and the mixture was
refluxed for 3 h. In the case of 2, the aqueous layer was removed and
extracted with diethyl ether (2×5 ml). The extracts were combined with
the organic layer and dried over CaCl2. The solvent was removed under
reduced pressure and the residue was distilled in vacuo to afford product 4.
In the case of 5, the solvents were removed, the solid residue was washed
with water and diethyl ether, and dried in vacuo to give compound 6.
2-{[(1,1,3,3,3-Pentamethyldisiloxanyl)methyl]sulfanyl}-1,3-benzo-
thiazole 4. Yield 0.34 g (87%), colourless viscous liquid with a specific
smell, bp 145–150°C (2 Torr). IR (film, n/cm–1): 1059 (Si–O–Si). 1H NMR
(acetone-d6) d: 0.14 (s, 9H, Me), 0.27 (s, 6H, Me), 2.68 (s, 2H, CH2S),
7.32 (dd, H4, 3JHH 8.2, 8.6 Hz), 7.42 (dd, H8, 3JHH 8.4, 8.6 Hz), 7.46 (d,
The study of the structures of the compounds obtained was
conducted using the equipment of Baikal Analytical Center for
Collective Use SB RAS.
3
3
H9, JHH 8.4 Hz), 7.81 (d, H4, JHH 8.2 Hz). 13C NMR (acetone-d6) d:
–0.28 (Me), 1.19 (Me), 19.57 (CH2), 121.24 (C4), 124.15 (C5,6), 126.16
(C7), 135.38 (C8), 153.76 (C9), 169.61 (SC). 15N NMR (acetone-d6) d:
–81.8. 29Si NMR (acetone-d6) d: 3.3, 9.4. Found (%): C, 47.55; H, 6.48;
N, 4.00; S, 19.49; Si, 16.84. Calc. for C13H21NOS2Si2 (%): C, 47.66;
H, 6.46; N, 4.28; S, 19.58; Si, 17.14.
References
1 (a) N. Herrera Cano, M. S. Ballari, A. G. López and A. N. Santiago,
J. Agric. Food Chem., 2015, 63, 3681; (b) M. A. Azam and B. Suresh, Sci.
Pharm., 2012, 80, 789; (c) F. Wang, S. Cai, Z. Wang and C. Xi, Org. Lett.,
2011, 13, 3202; (d) W. Chen, Y. Huang, S. R. Gundala, H. Yang, M. Li,
P. C. Tai and B. Wang, Bioorg. Med. Chem., 2010, 18, 1617; (e) L.-L. Jiang,
Y. Tan, X.-L. Zhu, Z.-F. Wang, Y. Zuo, Q. Chen, Z. Xi and G.-F. Yang,
J. Agric. Food Chem., 2010, 58, 2643; (f) D. Cressier, C. Prouillac and
P. Hernander, Bioorg. Med. Chem., 2009, 17, 5275; (g) D. Cressier,
C. Prouillac, P. Hernandez, C. Amourette, M. Diserbo, C. Lion and
G. Rima, Bioorg. Med. Chem., 2009, 17, 5275; (h) C. Franchini, M. Muraglia,
F. Corbo, M. A. Florio, A. Di Mola, A. Rosato, R. Matucci, M. Nesi,
F. van Bambeke and C. Vitali, Arch. Pharm. Chem. Life Sci., 2009, 342,
605; (i) W. Huang and G. F. Yang, Bioorg. Med. Chem., 2006, 14, 8280.
2 K. Ramadas and N. Janarthanan, Synth. Commun., 1999, 29, 1003.
2-{[3-(1,3-Benzothiazol-2-ylsulfanyl)methyl]-1,1,3,3-tetramethyl-
disiloxanylmethyl}sulfanyl-1,3-benzothiazole 6. Yield 0.27 g (90%),
white powder, mp 168–170°C. IR (KBr, n/cm–1): 1077 (Si–O–Si). 1HNMR
(CDCl3) d: 0.29 (s, 12H, Me), 2.65 (s, 4H, CH2S), 7.24 (dd, H8, 3JHH 8.2,
8.6 Hz), 7.36 (dd, H8, 3JHH 8.4, 8.6 Hz), 7.67 (d, H9, 3JHH 8.4 Hz), 7.83
3
(d, H8, JHH 8.2 Hz). 13C NMR (CDCl3) d: 0.50 (Me), 20.18 (CH2),
121.44 (C4), 124.10 (C5), 124.70 (C6), 126.16 (C7), 135.43 (C8), 153.61
(C9), 170.31 (SC). 15N NMR (CDCl3) d: –85.4. 29Si NMR (CDCl3) d: 5.1.
Found (%): C, 48.74; H, 4.64; N, 5.36; S, 25.89; Si, 11.34. Calc. for
C20H24N2OS4Si2 (%): C, 48.73; H, 4.90; N, 5.68; S, 26.02; Si, 11.40.
– 353 –

Mendeleev Commun., 2017, 27, 352–354
3 (a) M. A. Katkova, A. V. Borisov, G. K. Fukin, E. V. Baranov, A. S.
8 T. Nishio and K. Shiwa, Heterocycles, 2004, 62, 313.
9 F.-L. Wu, W. M. Hussein, B. P. Ross and R. P. McGeary, Curr. Org.
Chem., 2012, 16, 1555.
10 L. V. Zhilitskaya, N. O. Yarosh, L. G. Shagun, I. A. Dorofeev and L. I.
Larina, Chem. Heterocycl. Compd., 2015, 51, 381 (Khim. Geterotsikl.
Soedin., 2015, 51, 381).
11 (a) L. G. Shagun, I. A. Dorofeev, L. V. Zhilitskaya, L. I. Larina, N. O.
Yarosh, L. V. Klyba and E. R. Sanzheeva, Mendeleev Commun., 2015,
25, 34; (b) N. O.Yarosh, L. V. Zhilitskaya, L. G. Shagun, I. A. Dorofeev,
L. I. Larina and L.V. Klyba, Mendeleev Commun., 2016, 26, 426.
12 M. G. Voronkov, V. P. Meleshkevich andYu. A. Yuzhelevsky, Siloksanovaya
svyaz (Siloxane Bond), Nauka, Novosibirsk, 1976 (in Russian).
Averyushkin,A. G.Vitukhnovsky and M. N. Bochkarev, Inorg. Chim. Acta,
2006, 359, 4289; (b) L. Mishra, R. Vilaplana, V. K. Singh, A. K. Yadaw
and F. González-Vilchez, J. Inorg. Biochem., 2001, 86, 581.
4 (a) R. J. Zdrahala and I. J. Zdrahala, J. Biomater. Appl., 1999, 14, 67;
(b) G. M. Bernacca, I. Straub and D. J. Wheatley, J. Biomed. Mater.
Res., 2002, 61, 138; (c) J. A. Hyde, J. A. Chinn and R. E. Philips, Jr.,
J. Heart Valve Dis., 1999, 8, 331; (d) M. G. Voronkov, G. I. Zelchan and
E. Ya. Lukevits, Kremnii i zhizn (Silicon and Life), 2nd edn., Zinatne,
Riga, 1978 (in Russian); (e) C. A. Hufnagel, Med. Instrum., 1977, 11, 74.
5 Y. Hu, Z.-C. Chen, Z.-G. Le and Q.-G. Zheng, Synth. Commun., 2004,
34, 2039.
6 (a) T. Deligeorgiev, S. Kaloyanova, N. Lesev and J. J. Vaquero, Ultrason.
Sonochem., 2010, 17, 783; (b) A. Duarte, W. Cunico, C. M. P. Pereira,
A. F. C. Flores, R. A. Freitag and G. M. Siqueira, Ultrason. Sonochem.,
2010, 17, 281.
7 H. P. Narkhede, U. B. More, D. S. Dalal, N. S. Pawar, D. H. More and
P. P. Mahulikar, Synth. Commun., 2007, 37, 573.
Received: 17th November 2016; Com. 16/5096
– 354 –