Novel protocol for the synthesis of organic ammonium tribromides and investigation of 1,1′-(Ethane-1,2-diyl)dipiperidinium bis(tribromide) in the silylation of alcohols and thiols

Article abstract of DOI:10.1246/cl.140564

A novel and efficient protocol for the synthesis of organic ammonium tribromides (OATBs) is developed by using inexpensive and eco-friendly periodic acid as an oxidant for the conversion of Br^-to Br₃^-. The method does not use any mineral acid and metal oxidants. The protocol is utilized to synthesize a new bis(tribromide) viz., 1,1′-(ethane-1,2-diyl)dipiperidinium bis(tribromide) (EDPBT). EDPBT is investigated as a catalyst in the silylation of alcohols and thiols by HMDS (hexamethyldisilazane) under solvent-free conditions.

Full text of DOI:10.1246/cl.140564

Received: June 9, 2014 | Accepted: June 25, 2014 | Web Released: July 4, 2014
CL-140564
Novel Protocol for the Synthesis of Organic Ammonium Tribromides
and Investigation of 1,1¤-(Ethane-1,2-diyl)dipiperidinium Bis(tribromide)
in the Silylation of Alcohols and Thiols
Rupa R. Dey, Bappi Paul, Siddhartha S. Dhar,* and Sushmita Bhattacharjee
Department of Chemistry, National Institute of Technology Silchar, Assam 788010, India
(E-mail: ssd@nits.ac.in)
A novel and efficient protocol for the synthesis of organic
ammonium tribromides (OATBs) is developed by using
inexpensive and eco-friendly periodic acid as an oxidant for
the conversion of Br to Br3 . The method does not use any
mineral acid and metal oxidants. The protocol is utilized to
synthesize a new bis(tribromide) viz., 1,1¤-(ethane-1,2-diyl)di-
piperidinium bis(tribromide) (EDPBT). EDPBT is investigated
as a catalyst in the silylation of alcohols and thiols by HMDS
(hexamethyldisilazane) under solvent-free conditions.
mineral acids is still a challenge for synthetic chemists. Periodic
acid (H5IO6) is known to be used extensively in the oxidation
of alcohols to aldehydes and acids in the presence of a catalyst
like KBr and CrO3.19 Its role as an oxidant in the conversion of
¹
¹
¹
Br to Br+ in a catalytic cycle for transformation of alcohols to
aldehydes is known in the literature.19a However, an extensive
literature survey reveals that H5IO6 has never been used as an
¹
¹
oxidant in the conversion of Br to Br3 leading to the synthesis
of a wide variety of organic tribromide reagents. Moreover, it is
cheap, nontoxic, efficient, and easy to handle.
In the context of application of tribromides as a catalyst,
attention may be drawn to the importance of silylation of
alcohols and thiols by HMDS (hexamethyldisilazane). Protec-
tion of functional groups are indispensable in multistep reactions
for the synthesis of polyfunctional compounds.20 Formation of
silyl ether from a hydroxy or thiol group is most popular and a
widely used method specially in analytical chemistry.21 The
silylating reagents that are commonly used in the traditional and
conventional processes are SiCl,22 MeSiN=C(Me)OSiMe,23
Me3SiCl or MeSiOTf in presence of a base,24 etc. However,
many of these methods have demerits such as the lack of
reactivity, time consuming, difficulty in removing by-products,
and the use of cobases during silylation reactions.25 HMDS is
commercially available, cheap, noncorrosive, and easy to handle
for the formation of trimethylsilyl ether, which generates only
ammonia gas as by-product.26 A variety of catalysts, CuSO4¢
5H2O, Al(OTf)3, trichloroisocyanuric acid and I2, etc., have
been reported previously for the efficient synthesis of silylated
products.25,27 To our knowledge, N,N¤-heterocyclic bis(tribro-
mide)s have never been used as a catalyst in silylation reactions.
As a part of our continuous endeavor16-18 to develop new
protocols for the synthesis of OATBs, we report herein a new
synthetic procedure for the synthesis of OATBs including a new
N,N¤-heterocyclic bis(tribromide) compound viz., 1,1¤-(ethane-
1,2-diyl)dipiperidinium bis(tribromide) (EDPBT). The applica-
tion of EDPBT as a catalyst in silylation of some selectively
chosen alcohols and thiols is also presented in this paper.
A variety of QABs (quaternary ammonium bromides) were
converted to the corresponding tribromides by H5IO6 under
solvent-free conditions without the help of a mineral acid. In a
typical reaction, 10 mmol of tetrabutylammonium bromide was
mixed with 20 mmol of KBr and 20 mmol of H5IO6. The mixture
was agitated in a mortar for ca. 5 min where upon a bright red
orange color compound was observed, indicating the formation
Tribromide reagents, particularly organic ammonium tri-
bromides (OATBs), have received considerable interest in the
recent past due to their wide applicability as reagents and
catalysts in a variety of organic reactions.1 Tribromides, often
known as solid bromine, have already been established to be
superior to liquid bromine, NBS, Br2/HBr, and many other
traditional brominating reagents because of their easy-handling,
nonhazardous nature, mildness, efficiency, and selectivity.2
Among the various tribromides, quaternary ammonium tri-
bromides (QATBs), viz., tetrabutylammonium tribromide
(TBATB),3 benzyltrimethylammonium tribromide (BTMATB),4
pyridinium hydrotribromide (PyHTB),5 and cetyltrimethyl-
ammonium tribromide (CTMATB)3 are often used as useful
reagents and catalysts for a variety of organic functional group
transformations. Moreover, N-heterocyclic tribromides such
as quinoline hydrotribromide (QHTB),6 N-methylpyrroline-2-
one hydrotribromide (MPHT),7 DABCO tribromide,8 and
9
[BBIm]Br3 have been well documented in the literature as
useful reagents and catalysts in important organic transforma-
tions. A few N,N¤-heterocyclic bis(tribromide)s, which are
relatively less common, but most interesting are also found in
literature.10 Recently, Patel et al. have prepared 1,1¤-(ethane-
1,2-diyl)dipyridinium bis(tribromide) as stable bis(tribromide)
by using oxone.11 The compound is found to have vast utility
in organic reactions like bromination of organic substrates
(alkene, alcohols, and amines) and synthesis of heterocyclic
compounds.12
Conventionally, OATBs are prepared using liquid Br2 and/
or HBr, which are perilous and not favorable from an environ-
mental point of view.13 Over the last two decades or so, many
improved methods for the syntheses of tribromides, which are
considered to be environmental benign, have been reported in
the literature. A few of them worth mentioning are V2O5/
2¹
¹
¹
H2O2,14 MoO4 /H2O2,15 MnO4 /H+,16 (NH4)2S2O8/H+,17
NaOCl/H+,18 oxone,11 etc. In spite of several advantages, many
of such methods usually involve metals and mineral acids,
which still cause environmental concerns. Therefore, develop-
ment of newer strategies that do not require the use of metals and
of a Br3 anion. The product thus formed was extracted with
a minimum volume of ethyl acetate and dried over anhydrous
Na2SO4. The solvent was removed in vacuum to obtain the
corresponding tribromide compound in nearly quantitative yield
(Scheme 1).
Chem. Lett. 2014, 43, 1545–1547 | doi:10.1246/cl.140564
© 2014 The Chemical Society of Japan | 1545

EDPBT
2 equiv KBr
Where
R4N= Me4N
Et4N
R4NBr3
R4NBr
(2.5 mol %)
2 equiv H5IO6,
ground, r.t.
CH2OH
CH2OSiMe3
+ NH3
+
HMDS
Ground, r. t.
~ 5 min
n-Bu4N
cetyl-Me3N
95 %
(82-93 %)
benzyl-Me3N
Scheme 4. Silylation of benzyl alcohol catalyzed by EDPBT.
Scheme 1. Scheme depicting the synthesis of QATBs.
13C NMR spectrum of EDPBT where the peak at ¤ 44.6 is for
the ethylene carbon. The spectral data of the synthesized
tribromide compound is as follows. EDPBT: Orange compound;
Yield: 92% (0.603 g); UV-visible: 269 nm; FT-IR (KBr, cm¹1):
3276, 2933, 1467, 1443, 745, 187; 1H NMR ¤: 9.0 (s, 2H), 3.20
(t, J = 5.6 Hz, 4H), 1.99-1.94 (m, 8H), 1.74-1.69 (m, 12H);
13C NMR ¤: 22.2, 22.4, 44.6, 77.01; Anal. Calcd for
C12H26N2Br6 (MW: 677.75): Calcd. C, 21.26; H, 3.87; N,
4.13; Br, 70.74%. Found: C, 21.21; H, 3.81; N, 4.03; Br,
70.67%.
After the successful synthesis of EDPBT in nearly quanti-
tative yield, the next step is the investigation of its efficacy as
a catalyst in the silylation reaction. For this purpose, benzyl
alcohol (5a) was chosen as a model substrate (Scheme 4).
The reaction was carried out in the absence of solvent at room
temperature taking HMDS as the silylating agent. Initially,
20 mmol of 5a was mixed with catalytic amounts of EDPBT and
a small amount of silica gel, and the whole reaction mixture was
ground well followed by the addition of HMDS (dropwise) at
room temperature. TLC was run to monitor the reaction (10%
EtOAc/hexane). It took ca. 5 min to complete the reaction with
95% yield. The catalyst amount used for this trial reaction
is 2.5 mol %. We have varied the catalyst amount from 1 to
10 mol % and observed that from 2.5 to 10 mol % of the catalyst,
the yields and reaction times are almost the same for different
silylation products. However, when the catalyst amount was less
than 2.5 mol %, the reaction times were too long for obtaining a
significant yield of the products. The potential of HMDS as a
reagent was examined for the silylation of 5a both in the
presence and absence of solvents (ethyl acetate, MeCN, and
DMSO) using a catalyst. It was observed that a solvent-free
reaction leads to better yield of the product in lesser time.
Moreover, solvent-free reactions are preferable from the view-
point of the environment.
Br
Br
Br−
NH
(1 equiv)
2
NH
N
Br−
Magnetic Stirring
H
(5-10°C)
(Yield 95 %)
−
Br−
Br3
4 equiv KBr
NH
NH
NH
NH
Br−
4 equiv H5IO6
Ground, r.t.
−
Br3
(Yield 92 %)
Scheme 2. Formation of EDPBT from corresponding dibromide.
Scheme 3. A plausible mechanism showing the function of
H5IO6 in the tribromide synthesis.
The synthesis of bis(tribromide) was carried out in two
steps. The first step involves the exothermic reaction of
piperidine (10 mmol) with 1,2-dibromoethane (5 mmol) under
cold conditions (5-10 °C) to generate 1,1¤-(ethane-1,2-diyl)di-
piperidinium dibromide. In the second step, the dibromide thus
synthesized was converted to the corresponding bis(tribromide)
with the help of 4 equiv of KBr and 4 equiv of H5IO6
(Scheme 2).
The plausible mechanism of tribromide formation has been
depicted in Scheme 3. H5IO6 converts Br to HOBr, which in
After achieving success with 5a, we tried silylation by
choosing a host of substrates, which include aromatic, aliphatic,
and acyclic alcohols and thiols. All of these substrates were
silylated by pursuing similar reaction conditions mentioned for
5a affording products in very high yield, 80-95% and in a short
reaction time, 5-17 min (Table 1).
¹
the presence of an acid (inherent acidic property exerted by
¹
¹
periodic acid itself) transforms three equiv of Br to Br3 . The
tribromide thus formed was extracted with a minimum volume
of ethyl acetate.
All the synthesized tribromides are characterized by UV-
visible and FT-IR spectroscopic analysis. The anion, Br3
A plausible mechanism16b of alcohol and thiol silylation
catalyzed by tribromide may be depicted via Scheme 5. From
the mechanism, it is observed that the Br2 molecule generated
from EDPBT, in fact acts as the catalyst. Intermediate I and II
are produced in the catalytic loop. In the final step, silyl ether
and/or silyl thioether are formed along with NH3 as a by-
product and regeneration of Br2.
In conclusion, the present work demonstrates an efficient
and environmentally acceptable procedure for the development
of OATBs and a new bis(tribromide) compound. Bis(tribromide)
namely, 1,1¤-(ethane-1,2-diyl)dipiperidinium bis(tribromide) is
studied for its efficacy as a catalyst in the silylation of thiols and
¹
exhibits a strong absorption band in the range 260-280 nm and
a vibrational stretching frequency at 170 cm¹1, characteristic of
the tribromide anion.15,28 Additionally, they were also analyzed
by elemental analysis. The results obtained are consistent with
theoretical values. The new tribromide, EDPBT is characterized
by elemental analysis, UV-vis, FT-IR, and NMR (1H and 13C)
1
spectroscopy. In the H NMR spectrum of EDPBT, a peak at
¤ 3.20 is certainly for the ethylene protons attached to the N-
1
atoms. However, no such peak was observed in the H NMR
spectrum of piperidine. A similar result can be observed in the
1546 | Chem. Lett. 2014, 43, 1545–1547 | doi:10.1246/cl.140564
© 2014 The Chemical Society of Japan

Table 1. Silylation of alcohols and thiols by HMDS taking
EDPBT as catalyst
Proced. Int. 2007, 39, 403.
5
6
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Yieldc Time
Entry Reactanta
Productsb
/% /min
7
8
9
R. Hosseinzadeh, M. Tajbakhsh, H. Khaledi, K. Ghodrati,
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S. P. Borikar, T. Daniel, V. Paul, Synth. Commun. 2010, 40,
647.
1
2
3
4
5
6
7
8
9
n-BuOH (1a)
i-PrOH (2a)
t-BuOH (3a)
PhC2H4OH (4a)
PhCH2OH (5a)
n-BuOSiMe3 (1b)
i-PrOSiMe3 (2b)
t-BuOSiMe3 (3b)
PhC2H4OSiMe3 (4b)
PhCH2OSiMe3 (5b)
93
87
88
90
95
7
9
6
10
5
7
13
17
6
10
11
8
4-MeOPhCH2OH (6a) 4-MeOPhCH2OSiMe3 (6b) 80
C6H11OH (7a)
C10H7OH (8a)
n-BuSH (9a)
C6H11OSiMe3 (7b)
C10H7OSiMe3 (8b)
n-BuSSiMe3 (9b)
C6H11SSiMe3 (10b)
PhCH2SSiMe3 (11b)
PhSSiMe3 (12b)
83
82
87
90
85
91
88
82
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10 C6H11SH (10a)
11 PhCH2SH (11a)
12 PhSH (12a)
13 4-MePhSH (13a)
14
4-MePhSSiMe3 (13b)
C10H7SSiMe3 (14b)
9
14
C10H7SH (14a)
aReactions were conducted at room temperature using catalyst to
substrate to HMDS molar ratio of 1:40:20 under solvent-free
condition. bAll the products were first checked in TLC and then
identified by spectroscopic techniques (see Supporting Information).
cIsolated yield.
−
Br−
NH
Br3
NH
+
NH
NH
Br−
2Br2
−
Br3
15 U. Bora, M. K. Chaudhuri, D. Dey, S. S. Dhar, Pure Appl.
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(Me3Si)2NH
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1734. b) R. R. Dey, S. S. Dhar, Chin. Chem. Lett. 2013, 24,
866.
ROSiMe3 / RSSiMe3
+
Br2
+
NH3
ROH/RSH
[Me SiNH Br]
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Br
3
2
[(Me3Si)2NHBr]
Br
II
I
ROH/RSH
ROSiMe3 / RSSiMe3
Scheme 5. Plausible mechanism of EDPBT-catalyzed silylation.
21 G. van Look, G. Simchen, J. Heberle, Silylation Agents,
Fluke Chemie, Buchs, Switzerland, 1995.
22 A. Bartoszewicz, M. Kalek, J. Nilsson, R. Hiresova, J.
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silylation suggest that the procedure may serve as an efficient
alternative route for the protection of alcohols and thiols.
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Supporting Information is available electronically on J-STAGE.
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Chem. Lett. 2014, 43, 1545–1547 | doi:10.1246/cl.140564
© 2014 The Chemical Society of Japan | 1547