A recyclable fluorous hydrazine-1,2-bis(carbothioate) with NCS as efficient catalysts for acetalization of aldehydes

Article abstract of DOI:10.1039/c3nj41182f

A fluorous hydrazine-carbothioate organocatalyst was prepared. Together with NCS, the catalyst showed a good activity in acetalization of aldehydes and alcohols. It could be recovered from the reaction mixture by fluorous solid-phase extraction (F-SPE) with excellent purity for direct reuse.

Full text of DOI:10.1039/c3nj41182f

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A recyclable fluorous hydrazine-1,2-bis(carbothioate)
with NCS as efficient catalysts for acetalization of
aldehydes†
Cite this: NewJ.Chem., 2013,
37, 890
Received (in Porto Alegre, Brazil)
31st December 2012,
Yi-Wei Zhu, Wen-Bin Yi* and Chun Cai
Accepted 5th February 2013
DOI: 10.1039/c3nj41182f
www.rsc.org/njc
A fluorous hydrazine-carbothioate organocatalyst was prepared.
Together with NCS, the catalyst showed a good activity in acet-
alization of aldehydes and alcohols. It could be recovered from the
reaction mixture by fluorous solid-phase extraction (F-SPE) with
excellent purity for direct reuse.
The selective protection of aldehydes is an important way for
synthetic strategies. This acetalization with alcohols can be
promoted in the presence of Lewis acids,1 protic acids,2 transi-
tion metal complexes.3 Cheap and environmentally benign
catalysts such as resins, functionalized silica4 and polymer-
supported compounds5 have also been employed. However,
these methods require stoichiometric amounts of acid, long
reaction time or high temperature that may be incompatible
with other sensitive functional groups. In this respect, organo-
catalysts have advantages like low toxicity, operational simplicity
and efficiency over inorganic or metal-based catalysts and attract
much interest, but their major limitations for catalysis are high
catalyst loadings (up to 20 mol%) and the difficulty of recovering
the catalyst.6 An alternative strategy is to design efficient, recycl-
able and subsequently reusable versions of organocatalysts.7
The application of solid–liquid separations based on fluor-
ous silica gel (FSG)8 is operationally convenient and applicable
to substances that contain only relatively few fluorine atoms
such as light-fluorous reagents.15,16 This is a key finding since
light-fluorous reagents and catalysts have chemical and physical
properties that are similar to their non-fluorous counterparts.
Recently, fluorous organocatalysts have emerged as attractive
tools in Michael addition, Diels–Alder reaction as well as 1,3-
dipolar cycloaddition with high recyclability.9 Compared to
Fig. 1 Fluorous hydrazine-1,2-bis(carbothioate) 1 and hydrazine-1,2-dicarbox-
ylate 2.
recyclable heterogeneous organocatalysts, the fluorous organo-
catalysts are soluble in common organic solvents, thus they can
be easily separated and recovered from the reaction mixture by
fluorous solid-phase extraction.10
In the course of our extensive synthetic and physical inves-
tigations involving substituted hydrazinecarbothioate and
hydrazinecarboxylate, also, inspired by a fluorous tag idea11
and recent reports,12 our group tried to examine whether the
substituted hydrazinecarbothioate or hydrazinecarboxylate
with NCS could catalyze acetalization reaction efficiently by
means of hydrogen-bonding. We successfully employed the
combination in the synthesis of polysubstituted 1,2-dihydro-
quinolines via tandem reaction of a-ketonesters and arylamines.13,14
So we applied the fluorous hydrazine-1,2-bis(carbothioate) 1
and hydrazine-1,2-dicarboxylate 2 (Fig. 1) with NCS to one of
the most fundamental and significant C–X bond forming
reactions: acetalization of aldehydes and alcohols. To our
delight, the catalyst exhibited an excellent catalytic activity in
acetalization.17,18
School of Chemical Engineering, Nanjing University of Science and Technology,
Xiao Ling Wei Street, Nanjing 210094, People’s Republic of China.
E-mail: yiwenbin@mail.njust.edu.cn; Fax: +86-25-84315030
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3nj41182f
Results and discussion
The fluorous hydrazine-1,2-bis(carbothioate) 1 and hydrazine-
1,2-dicarboxylate 2 were synthesized as shown in Scheme 1.
c
890 New J. Chem., 2013, 37, 890--892
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Table 2 NCS and 1 catalyzed acetalization of a variety of aldehydes with methanola
Entry
R
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
i-C3H7
2
2
1
1
1
1
1
1
1
5
34
72
87
90
93
96
96
98
88
47
n-C3H7
n-C6H13
n-C7H15
n-C8H17
n-C9H19
n-C10H21
n-C11H23
PhCH2CH2
Ph
Scheme 1 Preparation of fluorous hydrazine-1,2-bis(carbothioate) 1 and hydra-
zine-1,2-dicarboxylate 2.
2-Perfluorohexyl ethanol II was treated with 1,10-(thio)carbonyl
diimidazole I at room temperature. Quenching with water and
extraction with petroleum ether provided crude product III,
after purification in a column, compound III reacted with
hydrazine monohydrochloride and triethylamine. The fluorous
hydrazine (1, 2) was isolated as a white powder.
a
The reaction conditions: RCHO (2 mmol); methanol (6 mL); 5 mol%
b
NCS; 5 mol% 1. GC yield based on RCHO.
alcohol (Table 1, entry 8) in the acetalization, no significant
change in reaction duration or yield was produced. However,
the use of the more sterically hindered 2-propanol gave a slower
reaction with a lower yield (Table 1, entry 9). The employment
of ethylene glycol afforded a good yield, but the reaction
proceeded extremely slowly (Table 1, entry 10).
Various aldehydes were subsequently investigated. As
revealed in Table 2, all reactions proceeded efficiently to furnish
the products in moderate to excellent yields (34–98%). With the
increase of the carbon chain of aldehyde, the yield of
the acetalization increased as well (Table 2, entries 2–8). The
employment of iso-butylaldehyde gave a lower yield than that of
n-butylaldehyde (Table 2, entries 1 and 2). Ultimately, aromatic
aldehydes were investigated and they afforded moderate to
good yield (Table 2, entries 9 and 10).
Next, we performed the catalyst-recovery experiment using
2 mmol of aldehyde and 5 mol% of NCS and compound 1
(Scheme 2). After completion of the reaction, the mixture was
concentrated and then loaded onto a FluoroFlashs silica gel
cartridge for F-SPE. It was found that the catalyst could be
recovered in high yield (88–92%) with excellent purity (99%).
The recycling reactions using the recovered catalyst were
conducted 3 times as shown in Scheme 2 and the model
reaction could still afford 75% yield after 3 times recovery of
the fluorous catalyst.
We first carried out a model reaction involving 3-phenylpro-
pionaldehyde, NCS, fluorous catalysts and different alcohols to
optimize the reaction conditions. As could be seen from
Table 1, both the structure of catalyst and the catalyst loading
had pronounced effects on the yield. The combinations of
catalysts were investigated (Table 1, entries 2 and 4). As a result,
compound 1 was more efficiently structured compared to 2 in
the catalysis together with NCS. The effect of catalyst loading
was also evaluated (Table 1, entries 1–3). When 5 mol% NCS
and 5 mol% compound 1 were used, the reaction was acceler-
ated and afforded the product in 88% yield, and the catalytic
combination was found to be the most efficient and economic.
Without compound 1 aldehyde transformation was slow
(Table 1, entry 6) and the reaction gave only a trace amount
of the product in the absence of NCS (Table 1, entry 5).
Different acetal protection groups were then explored. Suitable
economic and high yielding conditions (5 mol% NCS/5 mol% 1)
were selected to study the effects of varying the alcohol. When
methanol was replaced with ethanol (Table 1, entry 7) or benzyl
Table 1 NCS- and 1 or 2-catalyzed acetalization of 3-phenylpropionaldehyde
with alcoholsa
The mechanism of this reaction is not very clear. One
explanation is that NCS by means of hydrogen bonding could
act as a precursor for the formation of Cl+, which in turn could
Entry
Catalyst (mol%)
ROH
Time
Yieldb (%)
1
2
3
4
5
6
7
8
NCS (10) + 1 (10)
NCS (5) + 1 (5)
NCS (5) + 1 (2)
NCS (5) + 2 (5)
1 (20)
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
BnOH
40 min
1 h
1.5 h
4 h
24 h
10 h
1 h
1 h
2 h
4 d
90
88
82
63
Trace
82
86
83
62
NCS (100)
NCS (5) + 1 (5)
NCS (5) + 1 (5)
NCS (5) + 1 (5)
NCS (5) + 1 (5)
9
iPrOH
HOCH2CH2OH
10c
82
a
The reaction conditions: 3-phenylpropionaldehyde (2 mmol); alcohol
b
c
(6 mL); 25 1C. GC yield based on 3-phenylpropionaldehyde. Ethylene
glycol (2 mmol), anhydrous THF (6 mL).
Scheme 2 Catalyst recycling experiment.
c
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extraction with excellent purity. Application of this catalyst for
other reactions is under investigation and will be reported in
due course.
Acknowledgements
The authors gratefully acknowledge the financial support of
National Natural Science Foundation of China (20902047),
Jiangsu Provincial Natural Science Foundation of China for
Key Projects BK2010070, NUST Excellence Initiative Funding,
NUST Research Funding (2011ZDJH07).
Fig. 2 Speculated key step in the catalytic process.
Notes and references
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a
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ˇ
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Chem. Soc., 2012, 134, 8074.
c
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This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2013