Fe2(SO4)3·xH2O on silica: An efficient and low-cost catalyst for the direct nucleophilic substitution of alcohols in solvent-free conditions

Article abstract of DOI:10.1039/c3ra45772a

Fe₂(SO₄)₃·xH₂O on silica has been found to be a novel efficient catalyst for the direct nucleophilic substitution of alcohols in solvent-free conditions. In this reaction system, the alcohols can react with various nucleophilic reagents for the convenient construction of C-C bonds and C-N bonds with the benefits of high conversion, no requirement to use excessive amounts of the nucleophile, only a catalytic amount of iron catalyst required, solvent-free and benign reaction conditions, and the feasible reusability of the catalyst.

Full text of DOI:10.1039/c3ra45772a

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Fe2(SO4)3$xH2O on silica: an efficient and low-cost
catalyst for the direct nucleophilic substitution of
alcohols in solvent-free conditions†
Cite this: RSC Adv., 2014, 4, 4286
Received 12th October 2013
Accepted 6th November 2013
*
Lingjun Li, Anlian Zhu, Yuqin Zhang, Xincui Fan and Guisheng Zhang
DOI: 10.1039/c3ra45772a
www.rsc.org/advances
Fe2(SO4)3$xH2O on silica has been found to be a novel efficient catalyst believed to be a rising star in metal catalysis.13,14 Here, the
for the direct nucleophilic substitution of alcohols in solvent-free commercial iron salt Fe2(SO4)3$xH2O supported on silica gel
conditions. In this reaction system, the alcohols can react with various was found to be an efficient heterogeneous catalyst for direct
nucleophilic reagents for the convenient construction of C–C bonds nucleophilic substitution reactions of alcohols under mild
and C–N bonds with the benefits of high conversion, no requirement conditions. This catalytic system has a wide substrate tolerance
to use excessive amounts of the nucleophile, only a catalytic amount with high conversion and selectivity, even in the water envi-
of iron catalyst required, solvent-free and benign reaction conditions, ronment of the iron salt and hydroxyl groups on silica, and
and the feasible reusability of the catalyst.
benets from no requirement to use excessive amounts of the
nucleophile, an easy work-up and the feasible reusability of the
catalyst. The possible mechanism for the excellent performance
of this catalytic system has also been proposed in this work.
The performances of different catalytic systems based on
Fe2(SO4)3$xH2O was studied using the reaction between ben-
zoylacetone 1a and benzhydryl alcohol 2a as a model and the
results are collected in Table 1. It was found that when this
reaction was conducted in traditional solvents such as CH2Cl2
and CH3NO2 at room temperature or under reux conditions,
the reaction was sluggish and the target compounds were poorly
obtained even aer 5 hours. When the reaction was conducted
in water at room temperature, the reaction did not proceed, but
under reux conditions, the target compound was produced in
10% yield aer 5 hours, suggesting that water is not strictly
forbidden in this reaction when catalysed with Fe2(SO4)3$xH2O.
It is well known that silica gel has a high adsorptive ability and
the hydroxyl groups together with adsorbed water on its surface
can form local hydrophilic centers. This has found interesting
applications in organic synthesis recently.15,16 Interestingly, in
this work, we found that when the iron salt Fe2(SO4)3$xH2O was
supported on silica, which has no obvious catalytic activity by
itself (entry 11, Table 1), the yield of the target compound was
signicantly increased. Additionally, when the reaction was
conducted at a temperature of 75 ꢀC, the target compound
was almost quantitatively isolated within 0.5 hours (entry 10,
Table 1).
Alcohols are desirable substrates for nucleophilic substitution
reactions to construct C–C and C–X bonds, and the activation of
the hydroxyl group is essential for related reactions.1,2
Numerous catalysis systems have been developed for this
transformation, but they oen suffer from low reactivity, low
selectivity, the necessary use of organic volatile solvents and an
anhydrous environment, the use of excessive amounts of the
nucleophile, and difficulties in reusing the catalyst.3–10 Recently,
Cozzi et al.11 found that when the substitution reactions of
alcohols was conducted “on water”, the hydroxyl group of the
alcohol was activated by the water molecules on the surface, and
converted to carbocations which reacted with the correspond-
ing nucleophiles. However, the reaction substrates are very
limited due to the strong nucleophilicity of water. In our
previous work,12 we also developed an interesting catalytic
system based on ionic liquids for this transformation, but the
reaction system still suffered from the use of high reaction
temperatures partly due to the high viscosities of the ionic
liquids themselves. Therefore, there is still a great necessity to
develop efficient catalytic systems which allow this trans-
formation to proceed under benign reaction conditions.
Beneting from its low cost, relatively non-toxic nature,
distinct Lewis acid character and feasible accessibility, iron is
The high catalytic activity of Fe2(SO4)3$xH2O supported on
silica for the model reaction encouraged us to investigated the
substrate scope of this method for the direct nucleophilic
substitution of alcohols. The successful results are collected in
School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical
Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang,
Henan 453007, P. R. China. E-mail: anlian_cn@aliyun.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra45772a
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Table 1 Fe2(SO4)3$xH2O catalyzed direct nucleophilic substitution reactions of benzhydryl alcohol
Solvent or
medium
Temperature
(ꢀC)
Isolated yield
(%)
Entrya
Time (h)
1
2
3
4
CH2Cl2
CH2Cl2
CH3NO2
CH3NO2
H2O
25
Reux
25
Reux
25
5
5
5
5
0
0
30
55
0
5
5
6
7
8
9
H2O
Reux
r.t.
35
55
75
5
5
0.5
0.5
0.5
0.5
10
10
41
89
98
Trace
Silicab
Silicab
Silicab
Silicab
Silicab
10
11c
75
a
1a (0.25 mmol), 2a (0.25 mmol) and Fe2(SO4)3$xH2O (12.5 mg, 0.025 mmol) in 5 mL of solvent were stirred at a certain temperature. b 200 mg silica
gel was used as the reaction medium. c In the absence of Fe2(SO4)3$xH2O.
Table 2. It was found that, besides benzoylacetone 1a, silica promotes bis(4-methoxyphenyl)methanol to efficiently
1,3-dicarbonyl compounds such as acetylacetone 1b and ethyl produce the bis(4-methoxyphenyl)methyl cation. The resulting
acetoacetate 1c could also react with benzhydryl alcohol 2a mixture of Fe2(SO4)3$xH2O–silica and the bis(4-methox-
smoothly and gave excellent isolated yields within 0.5 hours yphenyl)methyl cation could keep the red colour for over
(Table 2, entry 1–3). N-Nucleophiles such as nitroaniline 1d,
1
hour in an air atmosphere, which implied that
sulfonamide 1e, amide 1f, and 2,4-DNPH 1g also reacted Fe2(SO4)3$xH2O–silica can stabilize the active bis(4-methox-
smoothly with a stoichiometric amount of the alcohol to give yphenyl)methyl cation. However, when a drop of ethyl acetate
the N-alkylation products with good to excellent yields in 0.5–1 was added into this mixture, the red colour disappeared
hour (Table 2, entry 4–7). The scope of this reaction with respect immediately, which indicated that organic solvent destabilized
to the alcohol substrates was also examined (Table 2, entry 8– the bis(4-methoxyphenyl)methyl cation (photograph (d) in
15). It was shown that the benzhydryl alcohol with chlorine Fig. 1).
substituents 2b could react with the dicarbonyl compound 1a
Based on the above experiments, a plausible reaction
and nitroaniline 1d smoothly to give almost quantitative iso- mechanism based on the model reaction is proposed, as illus-
lated yields (Table 2, entries 8 and 9). The benzhydryl alcohol trated in Fig 2. Water from Fe2(SO4)3$xH2O or from the atmo-
with strong withdrawing substituents 2c could react with sphere is adsorbed on the surface of the silica gel, and forms
nitroaniline 1d at room temperature to give a quantitative iso- hydrogen bonds with the surface hydroxyl groups of the silica,
lated yield in 1 hour (Table 2, entry 10). Benzylic alcohols 2d–2f producing hydrophilic cores. The hydroxyl group of a benz-
could react with sulfonamide 1e smoothly to give excellent hydryl alcohol molecule is attracted to a hydrophilic core
yields under mild conditions (Table 2, entries 11–13). Allyl through the formation of a hydrogen bond with the hydroxyl
alcohol 2g was also found to be a suitable substrate for this group of silica or the adsorbed water. It is then activated to its
direct nucleophilic substitution reaction using this catalytic carbocation catalysed by the Lewis acid Fe2(SO4)3$xH2O. The
system, and gave the desired product in 93% yield within 0.5 formed carbocation, which is hydrophobic, then leaves the
hours (Table 2, entry 14). Moreover, primary alcohol 2h could hydrophilic core and is attacked by a benzoylacetone molecule
react effectively with 1a to give product 3o in 92% yield (Table 2, to form the target compound.
entry 15).
Furthermore, the reusability of this catalytic system for
Additional experiments were designed to illustrate the role direct nucleophilic substitution reactions was also investigated
of Fe2(SO4)3$xH2O–silica on the promotion of the reaction from the point of green chemistry. The results are collected
procedure. Bis(4-methoxyphenyl)methanol 2c was selected as a in Table 3. It was found that the supported iron salt,
model, which could produce a red bis(4-methoxyphenyl) Fe2(SO4)3$xH2O, could be reused without any signicant
methyl cation 4[+] (Fig. 1). By comparing photographs (a), (b) decrease in the catalytic activity. The ‘cross reuse’ experiment
and (c) in Fig. 1, it can be concluded that Fe2(SO4)3$xH2O– showed that the recovered catalyst could be reused for different
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Table 2 Direct nucleophilic substitution reactions of alcohols with N-nucleophiles and C-nucleophiles catalyzed by Fe2(SO4)3$xH2O on silica
Entrya
Nucleophiles
Alcohol
Products
Temperature (ꢀC)
Time (h)
Isolated Yield (%)
1
2a
75
0.5
98
2
3
4
2a
2a
2a
75
75
75
0.5
0.5
0.5
89
90
95
5
6
2a
75
75
0.5
92
85
2a
1
7
2a
75
0.5
81
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Table 2 (Contd.)
Entrya
Nucleophiles
Alcohol
Products
Temperature (ꢀC)
Time (h)
Isolated Yield (%)
8
2b
75
0.5
97
9
2b
75
0.5
96
10
2c
r.t.
1
95
11
12
13
2d
2e
2f
75
75
r.t.
0.5
0.5
1
90
89
91
14
2g
75
0.5
93
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Table 2 (Contd.)
Entrya
Nucleophiles
Alcohol
Products
Temperature (ꢀC)
Time (h)
Isolated Yield (%)
15
2h
75
1
92
a
Reaction conditions: 1 (0.25 mmol), 2 (0.25 mmol), Fe2(SO4)3$xH2O (12.5 mg, 0.025 mmol), and silica gel (200 mg) were stirred under certain
temperature.
Fig. 1 (a) Mixture of the silica gel and 2c; (b) mixture of Fe2(S-
O4)3$xH2O on silica; (c) mixture of the Fe2(SO4)3$xH2O–silica gel and
2c; (d) mixture of the Fe2(SO4)3$xH2O–silica gel and 2c after adding
ethyl acetate.
Fig. 2 A plausible reaction mechanism for Fe2(SO4)3$xH2O on silica
catalyzed direct nucleophilic substitution reactions of alcohols.
nucleophiles and alcohols with almost equivalent catalytic
performances compared to using the fresh catalyst, suggesting
its superior reusability.
Table 3 The reusability of Fe2(SO4)3$xH2O on silica for direct nucle-
ophilic substitution reactions of alcohols
In conclusion, this work has developed an efficient catalyst
system based on Fe2(SO4)3$xH2O on silica for direct nucleo-
Runa
NuH
Alcohol
Product
Time
Isolated yield (%)
philic substitution reactions of alcohols. The high conversion
and selectivity, wide substrate tolerance, low cost of the
catalyst, simple experimental process, solvent-free and
benign reaction conditions, and reusability of the catalyst
make this method attractive as a green chemistry process.
Additionally, the plausible reaction mechanism may give
some insight into the construction of novel alcohol activation
systems.
1
2
3
4
5
1a
1a
1a
1a
1d
2a
2a
2a
2b
2a
3a
3a
3a
3h
3d
0.5
0.5
0.5
0.5
0.5
98
95
95
96
95
a
All the reactions were conducted with the recovered Fe2(SO4)3$xH2O
on silica under 75 ꢀC.
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Experiment section
Acknowledgements
General
This work was supported by the National Natural Science
All of the alcohols, 1,3-dicarbonyl compounds, amide, sulfon- Foundation of China (Grant 20903037, 21172058), and the
amide and 2,4-DNPH were purchased from Aldrich, Alfa Aesar Research Fund for the Doctoral Program of Higher Education of
and Fluka and were used as received. Hydrated ferric sulfate of China (20094104120003).
A. R. grade was purchased from Beijing Chemical Factory, and
the content of Fe(III) was 21–23% (w/w). Melting points were
measured using a XRC-1 Microscopic Melting Point Measurer
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