Highly efficient recyclable sol gel polymer catalyzed one pot difunctionalization of alkynes

Article abstract of DOI:10.3390/molecules23081879

Amino-bridged gel polymer P1 was discovered to catalyze alkyne halo-functionalization in excellent yields, regioselectivity, functional group compatibility, and recyclability. We have observed that both aromatic and aliphatic alkynes can be converted to α,α-dihalogenated ketones in the presence of polymer P1 under metal-free conditions at room temperature within a short reaction time.

Full text of DOI:10.3390/molecules23081879

molecules
Communication
Highly Efficient Recyclable Sol Gel Polymer
Catalyzed One Pot Difunctionalization of Alkynes
Justin Domena 1, Carlos Chong 1, Qiaxian R. Johnson 2, Bhanu P. S. Chauhan 2,
*
ID
and Yalan Xing 1,
*
1
Department of Chemistry, William Paterson University of New Jersey, 300 Pompton Rd,
Wayne, NJ 07470, USA; domenaj@student.wpunj.edu (J.D.); chongc@student.wpunj.edu (C.C.)
Engineered Nanomaterials Laboratory, Department of Chemistry, William Paterson University of New
Jersey, 300 Pompton Rd, Wayne, NJ 07470, USA; johnsonq6@wpunj.edu
2
*
Correspondence: Chauhanbps@wpunj.edu (B.P.S.C.); Xingy@wpunj.edu (Y.X.);
Tel.: +1-973-720-2470 (B.P.S.C.); Tel.: +1-973-720-3462 (Y.X.)
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 19 June 2018; Accepted: 24 July 2018; Published: 27 July 2018
Abstract: Amino-bridged gel polymer P1 was discovered to catalyze alkyne halo-functionalization in
excellent yields, regioselectivity, functional group compatibility, and recyclability. We have observed
that both aromatic and aliphatic alkynes can be converted to
α,α-dihalogenated ketones in the
presence of polymer P1 under metal-free conditions at room temperature within a short reaction time.
Keywords: green catalysis; sol gel based catalysts; bromination; alkyne; halo-functionalization;
one-pot; organosilane
1. Introduction
Alkyne difunctionalization reactions, the addition of two functional groups across a triple bond,
are an efficient method for converting carbon-carbon triple bonds to valuable structures [1–5]. We have
been particularly interested in difunctionalization of alkynes for the selective synthesis of mono- and
di-halogenated ketones. Very recently, an efficient halo-functionalization of alkynes was developed by
our research lab to selectively prepare
iron and gold catalysis respectively (Scheme 1A) [
intermediates in organic synthesis and medicinal chemistry [
α
,
α
-dihalogenated ketones and
]. Halogenated ketones are versatle synthetic
]. As part of our continued interest for
α-halomethyl ketones using
6,7
8
the development of a more efficient and green alkyne difunctionalization methodology, for instance,
without the use of metal catalysts, we were intrigued by the possibility of using functionalized silicon
based polymers as heterogeneous catalysts.
This study was spurred by the accidental discovery that in the presence of silica gel, partial
halo-functionalization of alkynes took place. This observation led us to investigate the catalytic
activity of tailor-made silica based materials. In this communication, we present our findings
of amino-bridged silsesquioxanes catalyzed halo-functionalization of alkynes for the synthesis of
α
,
α
-dihalogenated ketones (Scheme 1B). This transformation was found to furnish an excellent yield of
desired -dihalogenated ketones in high selectivity at ambient temperature under 40 min of reaction
α,α
time. The polymer catalyst was also found to exhibit excellent recyclability. Bridged silsesquioxanes
containing a nitrogen bridge have been the materials of interests as catalyst supports due to their
complexing abilities with a variety of species [
8
–13]. It is known that metal complexes can coordinate
with nitrogen containing silsesquioxanes to furnish heterogeneous recyclable catalysts [14
–18]. While
looking for an economical and green process for alkyne difunctionalization reactions, we wanted to
explore the use of nitrogen containing silica materials as catalysts. This reasoning is based on the
Molecules 2018, 23, 1879; doi:10.3390/molecules23081879
www.mdpi.com/journal/molecules

Molecules 2018, 23, 1879
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fact that the bridged silsesquioxanes containing a nitrogen group can act as an “electrophile directing
channel” and may lead to better specificity [19–24].
Our previous report:
FeCl3 (5 mol %), NBS,
Present New Discovery:
O
then FeCl3/Silica gel (8% w/w)
R'
Br
R
O
X
Br
NXS, Acetone, H2O
R'
R
R'
R
X
Polymer Gel P1 (15% wt)
R
R'
X = Cl, Br, I
Au (III) (5 % mol), MeOH
1,4-dioxane
O
R'
R
NXS
X
X = Cl, Br, I
Scheme 1B
Scheme 1A
Scheme 1.
(1A) Alkyne difunctionalization and (1B) alkyne difunctionalization catalyzed by
polymer gel.
To examine this hypothesis, we utilized polysilsesquioxanes obtained after the hydrolytic
polycondensation of bis[3-(trimethoxysilyl)propyl] amine. The silane used in this process contains
Si-alkoxy groups at both ends and can undergo hydrolytic polycondensation reactions to provide
nitrogen functionalized silica materials. The gelification of bridged silanes is a very well-known
process and there have been various studies in which highly cross-linked silica has been produced
under various reaction conditions in presence of an acid or base catalyst [25]. The gelification reactions
have been carried in the presence or in absence of a co-gelifying agent such as tetraalkoxy silanes.
2. Results
In terms of catalyst preparation, our goal was to preserve a favorable amount of alkoxy groups on
silicon to produce methoxy substituted polycondensates which are known to possess the possibility
of “self-healing” via cross linking reactions in water mediated reactions [21,23]. Due to this reason
cogelifying agents were avoided. After using known protocols and other variations, we found that,
the hydrolytic polycondensation of the precursor bis[3-(trimethoxysilyl)propyl]amine in wet methanol
for six hours under ambient reaction conditions and in open air produces colorless silica gel, P1, which
still has a significant amount of Si-alkoxy groups (Scheme 2). At the initial addition of the solvent to
precursor bis[3-(trimethoxysilyl)propyl]amine, there appears to be no visible change. Times for gel
formation range from 6 h for 1 mmol and 16 to 22 h for 5 mmol of the reactants.
Over the course of gelification, NMR spectroscopy shows a small reduction of Si–O–CH3 protons
indicating a formation of gel through the polymerization and condensation networking of P0 via the
formation of Si–OH bonds leading to creation of Si–O–Si networks and methanol. The structural
characteristics of the resulting gels were verified by various techniques (see supplementary materials).
The solid state NMR studies clearly (Figure 1) showed the presence of residual Si–OCH3 groups
in resulting silsesquioxanes gel P1. The characteristic chemical shifts were similar to liquid phase
NMR data of the precusorsor. The residual Si–O–CH3 carbon appears at 52.40 ppm as a sharp peak.
The carbon to the nitrogen appears slightly further downfield at 55.17 ppm. The signal due to carbon
to silicon and nitrogen appears at 25.82 ppm. The carbon to silicon appears as a broad peak at 12.55
and 10.88 ppm due to the network interconnectivity of the Si–O–Si framework. The solid state 29Si
spectra (see supplementry material) further confirmed the structural assignments. The three peaks
−
47.26,
Si(T0) atoms confirming the residual Si–O–CH3 groups. Thepeak centered at
to Si(T1) atoms and the peak at 64.4 ppm corresponds to Si(T2) atoms. After thorough analysis of the
catalyst gel, we started our catalytic investigation by using phenyl acetylene 1a as the model substrate
−
56.52, and
−
64.47 were observed in 29Si NMR.The peak centered at
56.52 ppm was assigned
−
47.26 is assigned to
−
−

Molecules 2018, 23, 1879
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to optimize reaction conditions. The reaction was conducted with the integration of an organosilane
polymer P1 as a catalyst and N-bromosuccinimide (NBS) as an electrophilic bromine source (Table 1).
Consistently, the reaction progress was both scrutinized and monitored using TLC and GC-MS.
Scheme 2. Synthetic strategy to amino-bridged gels.
Table 1. Optimization of reaction conditions for the synthesis of α,α-dibromoketones.
Yield [b]
Entry [a]
Catalyst
H2O Equiv.
Solvent (1.25 mL)
2a
3
1
2
3
4
5
6
7
8
9
Gel P1
Gel P1
Gel P1
Gel P1
Gel P1
Gel P1
Silica gel [c]
No
5
5
5
1,4 Dioxane
Acetonitrile
THF
Acetone
Acetone
Acetone
Acetone
Acetone
Acetone
0
6
0
45
53
90
68
78
0
16
23
24
5
6
8
10
10
0
5
10
50
50
50
0
No
[a]
Reaction condition: phenyl acetylene (0.5 mmol), NBS (2.00 mmol), solvent (3 mL), and catalyst (15 wt. %) at
[b]
[c]
room temperature for 40 min.
GC yield. Silica gel 60 (230–400 mesh).
After a period of intensive investigation, the desired product
in both good yield and excellent selectivity over the tri-substitution product
as the solvent (entry 4). It was found that 1, 4-dioxane and THF as solvent only produced undesired
product and no desired product 2a was observed (entry 1 and 3). Acetonitrile gave less yield and
α
,
α
-dibromoketone 2a was obtained
3
when acetone was used
3
worse selectivity of the desired product compared to acetone (entry 2). Then the amount of additive
H2O was increased from 5 equivalents to 10 and 50 equivalents in acetone to improve both yield
and selectivity. To our delight, the utility of polymer P1 in the presence of 50 equivalennts of H2O in
acetone at room temperature was found to be the optimal conditions (entry 6) which generated the
desired product in 90% yields and gave high regioselectivity (90:8).

Molecules 2018, 23, 1879
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Figure 1. Solid state 13C-NMR of the amino-bridged gel P1.
We noticed that these results provided a clear indication of two major driving forces within our
one-pot reaction: both the necessity of water and the introduction of the sol-gel catalyst. To confirm
the importance of these two factors, we then decided to run a reaction without both water and gel
(entry 9). Not surprisingly, the reaction did not produce any products. Next, two control reactions
were run with regular silica gel (entry 7) and no polymer catalyst applied (entry 8). Both reactions
resulted with a decreased yield and regioselectivity of the major product. These results confirmed the
importance of our polymer catalyst P1 in terms of the yield and regioselectivity of this transformation.
With optimal conditions (entry 6, Table 1) in hand, the next phase initiated was the study of
substrate scope and limitation shown in Figure 2. In general, this reaction converts l alkynes to
α,α-dihalogenatedketones in good isolation yields. NBS (2a–2n), NCS (N-chlorosuccinimide) (2o),
and NIC (N-iodosuccinimide) (2p) were utilized as the halogen sources and all showed excellent
regioselectivity as well. Also, this reaction exhibits good functional group compatibility. Aromatic
compounds with a variation in both electron-donating and electron-withdrawing groups on the
benzene in different positions were explored. Substrates with halogens including: chlorine, bromine,
and fluorine on the different positions of the phenyl ring gave good to excellent yields (2b-2f). It is
also worth noting that strong electron-withdrawing fluorine groups showed decreased reaction yields
(
2d and 2e). In addition, alkyl substations such as 4-ethynyl-1,10-biphenyl, 1-ethyl-4-ethynylbenzene,
and 1-ethynyl-4-methoxybenzene produced a 72% (2h) yield, 84% (2g) yield, and 88% (2i), respectively.
Heterocyclic rings were also tolerated in this reaction condition and generated the desired products
in good yields (2j and 2l). In addition, not only terminal alkynes, but also an internal alkyne
(2k) underwent this reaction smoothly and gave good yield and regioselectivity of the desired
product. In which our reaction then proceeded to explore two aliphatic compounds; 1-nonyne and
1-heptyne. These two compounds were then observed to give acceptable yields of 66% (2m) and
45% (2n). Moreover, NCS and NIS also participated this transformation as halogen sources to give
α,α-dichloroketone (2o) and α,α-diiodoketone (2p) in excellent yields.

Molecules 2018, 23, 1879
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Figure 2. Substrate scope with isolated yields.
In order to further demonstrate the applicability of this gel catalyzed transformation, we tested
the recyclability of the catalyst under optimized reaction conditions. The transformation outlined in
entry 6 of Table 1 was used as standard protocol. To our delight, P1 was found to maintain similar
GC-conversion even after ten cycles (trial 10). A graphical representation with GC yields is shown in
Figure 3. This study clearly bodes well for the real world applications of our present catalytic system.
100
92
91
91
95
90
85
80
75
70
90
89
87
86
84
83
81
0
1
2
3
4
5
6
7
8
9
10
TRIALS 1‐10
Figure 3. Recyclability studies.
The detailed mechanistic studies are ongoing in our laboratories and will be presented in due
course. At this stage, based on the present results and the results of our previous study, we believe
that the use of the sol-gel polymer as a catalyst significantly increses the electrophilicity of NBS.
The increased electrophilicity is achieved via interaction of nitrogen of gel catalyst P1 (Scheme 2) with
the NBS bromine. This additional N–Br interaction increases the electrophilicity of Br and helps the
efficient delivery of Br+ in a highly regioselective manner.
3. Conclusions
In conclusion, we have revealed a very simple methodology to produce cross linked polymer
P1 using bis[3-(trimethoxysilyl)propyl] amine as precursor which was found to catalyze the one-pot
reaction of alkyne halo-functionalization to synthesize α,α-dihalogenated ketones. To our satisfaction,
our sol-gel catalyst P1 was then found to induce good reaction yields, to proceed under ambient
temperatures, and to exhibit excellent catalyst recyclability. The implications of this discovery are
promising in expanding the field of green chemistry centered synthesis via the utilization of a green
catalyst; as well as expanding the field of polymer chemistry pertaining to catalysis within an organic

Molecules 2018, 23, 1879
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synthesis reaction. Future studies of this phenomenon are currently being conducted within our
laboratory to further expand the scope of sol-gel catalysts utilized as well as the implementation of the
sol-gel catalysts within more complex organic synthetic methods.
Supplementary Materials: The following are available online, General procedure; preparation and characterization
of polymer catalyst P1; characterization of 1H and 13C NMR spectra of α,α-dihalogenated ketones.
Author Contributions: In this collaborative effort, the bridged silsesquioxanes synthesis and analysis investigation
were carried out by B.P.S.C. and Q.R.J. The catalytic explorations, optimization and difunctionalization product
synthesis and analysis were performed by Y.X., J.D., and C.C.
Funding: This research received no external funding.
Acknowledgments: The B.P.S.C. and Y.X. thank the Research Release Time awards of William Paterson University.
This research was supported (in part) by a grant from the Center for Research, College of Science and Health,
William Paterson University of New Jersey.
Conflicts of Interest: The authors declare no conflict of interest.
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