Polymethylhydrosiloxane reduction of carbonyl function catalysed by titanium tetrachloride

Article abstract of DOI:10.4314/bcse.v32i1.18

Reduction of aromatic aldehydes and ketones into the corresponding methylene derivatives by polymethylhydrosiloxane in the presence of titanium tetrachloride as catalyst was achieved in good to excellent yields ranging from 55-90%. The reaction took place under relatively mild conditions and smoothly led to the desired target molecules in the presence of other functional groups such as halogens, hydroxyl, nitro and methoxy groups. However, in the reduction of the substrate with two methoxy groups in close proximity (1,2-positions), the reaction necessitated a larger amount of the titanium catalyst and a longer reaction time to complete the reduction of the carbonyl function due to a likely complex formation of titanium tetrachloride with the methoxy groups.

Full text of DOI:10.4314/bcse.v32i1.18

Bull. Chem. Soc. Ethiop. 2018, 32(1), 179-184.
2018 Chemical Society of Ethiopia and The Authors
ISSN 1011-3924
Printed in Ethiopia

DOI: https://dx.doi.org/10.4314/bcse.v32i1.18
SHORT COMMUNICATION
POLYMETHYLHYDROSILOXANE REDUCTION OF CARBONYL FUNCTION
CATALYSED BY TITANIUM TETRACHLORIDE
*
Ndze D. Jumbam , Siyavuya Makaluza and Wayiza Masamba
Department of Chemical and Physical Sciences, Walter Sisulu University, Nelson Mandela
Drive, Mthatha 5117, South Africa
(Received October 11, 2017; Revised January 22, 2018; Accepted January 23, 2018)
ABSTRACT. Reduction of aromatic aldehydes and ketones into the corresponding methylene derivatives by
polymethylhydrosiloxane in the presence of titanium tetrachloride as catalyst was achieved in good to excellent
yields ranging from 55-90%. The reaction took place under relatively mild conditions and smoothly led to the
desired target molecules in the presence of other functional groups such as halogens, hydroxyl, nitro and methoxy
groups. However, in the reduction of the substrate with two methoxy groups in close proximity (1,2-positions), the
reaction necessitated a larger amount of the titanium catalyst and a longer reaction time to complete the reduction
of the carbonyl function due to a likely complex formation of titanium tetrachloride with the methoxy groups.
KEY WORDS: Carbonyl reduction, Polymethylhydrosiloxane, Titanium tetrachloride, Catalyst, Hydride
transfer
INTRODUCTION
The reduction of the carbonyl function of aldehydes and ketones to methylene is an important
reaction that has found wide applications in organic syntheses both in research laboratories and
also in the chemical industry. Various methods have been employed for this chemical
transformation but the Clemmensen [1] and Wolff–Kishner [2] reduction processes have thus far
exhibited the most general utility [3]. However, the drastic reaction conditions of both processes
have given rise to various other methods, all in an effort to find milder reaction conditions.
Some of the alternative methods include catalytic hydrogenation [4-5], reductions using Raney
nickel in hydroxide media [6], reductions using PtO [7], HI-phosphorus [8-9], NaBH
2
4
-
CF COOH [10-11], NaCNBH -BF Et O [12], LAH-AlCl [13]. While these methods offer some
3
3
3
2
3
advantages, they also suffer from some disadvantages. A good number of the methods are
limited to aromatic systems, others require the use of pyrophoric hydride source for reduction,
and some are prone to long reaction hours coupled with tedious workup and are associated with
low yields. Since silanes undergo hydride transfer to relatively stable carbenium ions, they have
been used to convert carbonyl function to methylene [3]. More recently, however, catalytic
reduction of the carbonyl group has been carried out in the presence of
polymethylhydrosiloxane (PMHS), an excellent hydride donor and cheap by-product of the
silicone industry, which is easy to handle and claimed to be environmentally friendly [14].
Jaxa-Chamiec and co-workers [15] reported the conversion of carbonyl group to methylene
using AlCl in the presence of PMHS. The inherent environmental problems associated with the
3
workup of AlCl
of carbonyl group to methylene has been described by Chandrasekhar and co-workers using
B(C as a nonconventional Lewis acid to activate PMHS [16]. Although the authors claimed
that the method reduced aromatic as well as aliphatic carbonyl compounds in good yields, the
high cost of B(C is prohibitive. A promising alternative was the microwave induced
3
reaction systems, render this process unsustainable. A rapid defunctionalisation
6 5 3
F )
6 5 3
F )
_
_________
*
Corresponding author. E-mail: njumbam@wsu.ac.za
This work is licensed under the Creative Commons Attribution 4.0 International License

180
Ndze D. Jumbam et al.
FeCl
3
.6H
2
O-catalysed reduction of ketones and aldehydes to alkane compounds developed by
Campagne and co-workers [14, 16] in which aromatic and aliphatic carbonyl compounds were
reduced in good yields.
South Africa has the world’s second deposits of titanium after Australia [17]. The east coast
of the country, more specifically much of Pondoland is awash with titanium sands. It could be
the gateway metal to a new golden age for South Africa. However, while titanium finds varied
applications in industry, its use in organic syntheses remains largely unexplored especially as a
reduction catalyst. Buchwald and co-workers [18] were able to reduce ketones and methyl esters
using a titanocene catalyst in the presence of PMHS. Reduction of the carbonyl functional group
of various substrates catalysed by titanium tetrachloride (tickle) in the presence of PMHS as a
hydride source in dichloroethane (DCE) is herein described by the authors of this paper for the
first time.
EXPERIMENTAL
General. All chemicals were obtained from commercial sources and were used without further
1
13
purification unless stated otherwise. Products were characterised by H- and C-NMR
spectroscopy using a Varian spectrometer at 400 and 100 MHz for proton and carbon-13,
respectively. Spectra were recorded from CDCl
3
solutions employing TMS as an internal
reference. All spectra are reported as  (ppm) values.
Representative procedure (compound 2).
A solution of 2-chloro-1-[4-(propan-2-
yl)phenyl]ethanone (1 g, 5.1 mmol) in dichloroethane (DCE) (10 mL) was placed in a 50 mL
three-mouth round-bottomed flask equipped with a reflux condenser, a calcium chloride drying
tube, a thermometer and a magnetic stirring bar. To the stirred reaction solution at room
temperature, tickle (0.115 mL, 25%) followed by PMHS (0.7 g, 12.2 mmol) were added from a
syringe. The reaction mixture was heated to reflux and progress of the reaction monitored by
thin layer chromatography (tlc) and stopped after three hours. The gelatinous reaction mixture
was taken up in hexane (15 mL) and filtered under a plug of celite. The filter cake was washed
with hexane (50 mL) and the filtrate concentrated in vacuo. The crude product was purified by
o
column chromatography on silica gel to give an oily product (0.75 g, ~79.4%); b.p.: 140 C/2.6
mm Hg.
1
H-NMR of 2. CDCl ): 1.11 (d, 6H, J = 7.14), 2.77 (sept, 1H, J = 7.01), 3.01 (t, 2H, J = 7.69),
3
1
3
3
3
.42 (t, 2H, J = 7.69), 7.01 (d, 2H, J = 8.24), 7.06 (d, 2H, J = 8.24). H-NMR; CDCl
3
): 23.96,
+
3.01, 33.71, 39.07, 126.63, 128.53, 136.20, 147.48; HRMS (EI ): calc. for C11
H15Br, 226.0357;
found 226.0361.
1
H-NMR of 4. CDCl ): 1.16 (d, 6H, J = 7.14), 2.81 (sept, 1H, J = 7.03), 2.96 (t, 2H, J = 7.56),
3
1
3
3
3
.62 (t, 2H, J = 7.41), 7.06 (d, 2H, J = 8.24), 7.11 (d, 2H, J = 8.24). H-NMR; CDCl
3
): 24.34,
+
4.08, 39.18, 45.41, 121.97, 129.07, 135.73, 147.81; HRMS (EI ): calc. for C11
H15Cl, 182.0822;
found 182.0777.
All products listed in Table 1 were prepared analogously to the representative procedure.
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Short Communication
181
Reference
This work
This work
[19]
[
20-21]
20-21]
[
[22]
[23-24]
[25]
[26]
[27]
RESULTS AND DISCUSSION
The reduction of carbonyl function by PMHS activated by tickle occurred smoothly and the
formation of a gelatinous precipitate signified the end of the reaction, which was confirmed by
Bull. Chem. Soc. Ethiop. 2018, 32(1)

182
Ndze D. Jumbam et al.
TLC. The reaction was complete in less than an hour with the use of 50% tickle. The tickle
concentration of 25% was maintained throughout the investigations and the reactions never
exceeded three hours.
Results of this reduction reaction are summarised in Table 1. Good to excellent yields were
achieved using this method. Entries 1, 2, 3, 7, and 8 indicate that the presence of halogens did
not interfere with the reduction reaction. It is noteworthy that reactions in entries 2 and 3 leading
to the formation of compounds 4 and 6, respectively, could be carried out at room temperature
affording the same products and yields. The high reactivity of the two substrates (3 and 5) may
be attributed to the activation of the carbonyl function by the halogen atoms. In the case of
substrate 3, two products were observed, irrespective of the reaction conditions utilised.
Compound 2 most likely originated from the attack by a chlorine ion from tickle on the
intermediate as outlined in Scheme 1 below:
Cl
Cl
Ti
Br
O
Cl
Br
TiCl4
2
O
H C
3
-
3
H C
Cl
CH3
CH3
Scheme 1
The reduction of 3 afforded a mixture of 2 and 4 in 73 and 27% yields, respectively. This
was found to be true when the reaction took place at room temperature and at refluxing
temperature. The identity of 2 was confirmed independently by the reaction of 4 with excess
sodium chloride in DMSO to afford the product in 90% yield. An attempt to carry out this
reaction in DMF resulted in substantial elimination of the halogen to form the corresponding
styrene derivative. However the best method to access compound 2 was through the reduction of
substrate 1 using the same methodology as shown in entry 1. To the best of our knowledge,
compounds 2 and 4 have not been described before.
It is also relevant to note that there is no direct conversion of compounds 5 and 15 to the
corresponding reduction products 6 and 16, respectively. Reduction of 5 by hydrogen transfer
reaction with formic acid in the presence of a ruthenium catalyst led only to the corresponding
chlorohydrin (2-chloro-1-phenylethanol [28].
Even though one methoxy group did not interfere in the reduction as shown in entry 4, the
two ether groups in close proximity (Entry 6) appeared to slow down the reaction but did not
completely inhibit it. The reaction required 60% of tickle and took six hours to complete, due
likely to the formation of a chelation complex with tickle that slowed down the reduction
process.
Surprisingly however, the nitro group in substrate 17 did not inhibit the reaction despite the
fact that its two oxygen atoms could potentially chelate the titanium ion. Unlike in all the other
entries in table 1, the reaction led to the formation of two products: the expected methylene
derivative and the corresponding alcohol. This is an indication that the reaction takes place in a
two-step process with the alcohol as the intermediate. This implies that with the use of
appropriate reaction conditions, it should be possible to stop the reaction at the alcohol stage or,
if so desired, carried on to the final step. The formation and isolation of the alcohol intermediate
may open up a new avenue for this reaction. For example, carbonyl derivatives such as imines
may be selectively reduced to the corresponding amines. The Clemensen and Wolff–Kishner
reductions on the other hand operate with completely different reaction mechanisms.
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Short Communication
183
Although the halogens have an inductive electron-withdrawing ability, substrates 1, 3, 5, 13,
and 15 revealed no noticeable influence on the outcome of the reaction.
The herein described PMHS reduction of aromatic aldehydes and ketones into the
corresponding methylene derivatives catalysed by tickle compared to the classical Wolff-
Kishner and Clemmensen processes has proven to be the method of choice. Its simplicity, safety
of operation, low cost and functional group compatibility outweighs those of other known
methods.
CONCLUSION
Carbonyl compounds were successfully reduced to the corresponding methylene derivatives
using the polymethylhydrosiloxane–tickle system as the reducing agent. The mild reaction
conditions, namely the ease of handling of the reagents, low reaction temperature, functional
group compatibility and easy reaction workup may pave the way for possible industrial
applications of this reduction reaction. The unexpected isolation of an alcohol intermediate in
one example gives insight into the possible reaction steps involved in the process.
In future investigations, attempts will be made to expand the scope of this reduction reaction
and perhaps determine its limitations by utilising a range of aliphatic and aromatic carbonyl
compounds with a variety of functional groups.
ACKNOWLEDGMENT
We thank the Directorate of Research Development at Walter Sisulu University for financial
support.
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