Fluorous 4-N,N-dimethylaminopyridium iodide: Recyclable organocatalysts by precipitation for acylation reaction at room temperature

Article abstract of DOI:10.1016/j.catcom.2013.06.031

A novel fluorous DMAP quaternary ammonium iodide salt organocatalyst was prepared. This fluorous organocatalyst was successfully employed to the acylation reaction at room temperature without the use of a stoichiometric amount of external base. It could be recovered 3 times from the reaction mixture by simple precipitation with excellent purity for direct reuse.

Full text of DOI:10.1016/j.catcom.2013.06.031

Catalysis Communications 41 (2013) 26–28
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Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Fluorous 4-N,N-dimethylaminopyridium iodide: Recyclable
organocatalysts by precipitation for acylation reaction at
room temperature
⁎
Wen-Bin Yi , Yi-Wei Zhu, Chun Cai
School of Chemical Engineering, Nanjing University of Science and Technology, Xiao Ling Wei Street, Nanjing 210094, People's Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel fluorous DMAP quaternary ammonium iodide salt organocatalyst was prepared. This fluorous
organocatalyst was successfully employed to the acylation reaction at room temperature without the use
of a stoichiometric amount of external base. It could be recovered 3 times from the reaction mixture by
simple precipitation with excellent purity for direct reuse.
Received 30 April 2013
Received in revised form 25 June 2013
Accepted 26 June 2013
Available online 3 July 2013
© 2013 Elsevier B.V. All rights reserved.
Keywords:
Fluorous organocatalyst
Fluorous 4-N,N-dimethylaminopyridium
iodide
Acylation
Recycling by precipitation
1. Introduction
of DMAP (1, Scheme 1) tagged with fluorous chains for the acylation re-
action in 2008 [26]. Quite recently, they prepared fluorous carboxylate
Compared with the traditional metal-based catalyst, organocatalyst
has drawn much attention, owing to its low toxicity, operational
simplicity and high efficiency [1,2]. However, the major disadvantages
of organocatalysts are high loading (up to 20 mol%) and difficulty of
reusing. The recyclability of organocatalysts are of prime interest for
the development of sustainable synthetic processes [3–5].
of DMAP (2, Scheme 1) as an active and recyclable acylation catalyst in
the absence of Et3N [27]. Herein, we report a novel fluorous DMAP qua-
ternary ammonium salt (3, Scheme 1) as an efficient organocatalyst for
the acylation reaction of alcohols with anhydrides at room temperature
without the use of a stoichiometric amount of external base, such as
Et3N and i-Pr2NEt.
DMAP (4-N,N-Dimethylaminopyridine) is a very effective nucleophilic
base catalyst for the acylation of alcohols with acid anhydrides and other
related reactions [6–11]. Unfortunately, this powerful organocatalyst ex-
hibit acute dermal toxicity [7]. To avoid this drawback, various recyclable
DMAP have been prepared through immobilization on organic or inor-
ganic supports [12].
Recently, fluorous technology has emerged as a new and powerful
protocol to recover and reuse catalyst [13–18]. This strategy originally
involved fluorous solvents [19] or silica gel [20], but the current trend
tends toward simple solubility modulation of fluorous catalysts in con-
ventional media, for recovery through precipitation [21–24]. Many
fluorous compounds tagged with one or two “Rf8” and “Rf10” ponytail
have little or no solubility in non-polar organic solvent such as octane
and hexane [25]. The strategy of recycling catalyst through precipitation
can be achieved by making organocatalyst bear a light fluorinated pony-
tail when using proper non-polar organic solvent as reaction media or as
extraction reagent. Legros group reported the preparation of analogues
2. Results and discussions
The fluorous DMAP quaternary ammonium iodide salts were
prepared by simply mixing amine with perfluoroalkyl iodide [28]. The
reaction of Rf8I did not give the corresponding quaternary ammonium
salts, and starting material was recovered (Scheme 2). Two fluorous
DMAP quaternary ammonium solids 3a (Rf = C6F13C2H4) and 3b
(Rf = C8F17C2H4) were obtained respectively from Rf6CH2CH2I, and
R
f8CH2CH2I perfluoroalkyl iodides, which have two methylene spacer
avoiding excessive electronic and steric perturbations (Scheme 2).
Based on the MS spectrometry, 1H NMR, 13C NMR and IR, it can be
concluded that the fluorous 4-N,N-dimethylaminopyridine quaternary
ammonium iodide salts were formed. Having the particular solubility
of perfluorinated molecules, fluorous DMAP quaternary ammonium
iodide salts 3a and 3b are different from DMAP and traditional quaternary
ammonium iodide salts, and show no solubility in H2O and AcOH. The
fluorous DMAP salts have much less solubility in fluorous solvents
(PFCs) such as perfluorohexane (C6F14, FC-72), perfluorooctane (C8F18
,
⁎
Corresponding author. Tel.: +86 25 84315514; fax: +86 25 84315030.
E-mail address: yiwenbin@mail.njust.edu.cn (W.-B. Yi).
FC-77), and methoxy-nonafluorobutane (C4F9OCH3, HFE-7100). They
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.06.031

W.-B. Yi et al. / Catalysis Communications 41 (2013) 26–28
27
the 19 F NMR, no loss of fluorous DMAP to the organic extraction can be
detected. The GC-MS of the organic phase showed that the reactions
gave pure products. Importantly, reuse of the precipitated fluorous
DMAP was equally effective without purification. For example, the
yields of acylation using 3b as catalyst from the first run to the third
run were 98%, 97%, and 94%, respectively (Fig. 1). By calculating weight
and detecting IR, 19 F NMR and 1H NMR, we found that the catalyst was
recovered in 93% yield and in 99% purity (Fig. 1). Iodide anion was pro-
posed to play the key role in this system, which has been reported
as catalyst for acylation reaction [32]. The free DMAP cannot be easy
generated because ammonium salts of DMAP with an alkyl halide are
highly stable. So, DMAP cation should not be a catalyst in this case.
To explore the generality and scope of 3b-catalyzed acylation under
auxiliary base- and solvent-free conditions, the reaction was examined
with various alcohols and acetic anhydrides (Table 2). Acylations of
primary and secondary alcohols proceeded well. Benzolic alcohols
with various substitutions such as Me- and NO2- and aliphatic alcohols
gave the corresponding esters in above 90% yield. Secondary alcohols
such as isopropyl alcohol and cyclohexanol reacted with acetic anhy-
dride to get acylation product in 95% and 92% yields respectively. Final-
ly, the 3b-catalyzed acylation of benzyl alcohol with acetic anhydride
was performed on a 10 g scale. After 24 h, hexane was used to extract
product ester and acetic acid. The acetic acid was collected for experi-
mental use. The catalyst was precipitated and fully recovered. The
hexane phase was distilled to afford ester in 92% isolated yield.
Rf
N
N
N
N
+
+
-
N
N
I
-
R
fCO2
Rf
H
=
Rf
F15 11F23
C7
C
=
,
=
C6 13C2
Rf
F15 11F23
C
,
C7
Rf
F
H4 8F H4
17C2
C
,
3
2
1
Scheme 1. Fluorous DMAPs and derivatives.
H
l
2C 2
C
N
+
RfI
N Rf
N
N
r
t 12h
,
I
=
=
=
no ro uc
t
d
p
Rf
Rf
Rf
F1
C8
,
7
a
3
e
i ld
9 %
y
F H4
C6 13C2
1
,
,
e
i ld
93%
y
F1
C8 7C2
H4
3
b
,
,
Scheme 2. Synthesis of fluorous DMAP iodide salts.
always appeared not to be soluble in non-polar solvents, such as hexane
and octane. These fluorous salts could be solubilized in MeOH, EtOH
and benzyl alcohol, which can offer an appropriate reaction medium for
acylation of alcohol.
3. Conclusions
In summary, a readily accessible and recyclable fluorous DMAP iodide
organocatalyst has been developed for the acylation reaction of alcohols
with anhydrides at room temperature. The reaction can be carried out
under auxiliary base- and solvent-free conditions, and the fluorous cata-
lyst can be recovered from the reaction mixture by simple precipitation.
The strategy provides a choice for practical esterification.
Initially, the reaction conditions for the acylation of benzyl alcohol and
acetic anhydride were investigated (Table 1). The control experiment
elucidated that only trace of acylation product could be obtained.
DMAP/Et3N and DMAP/i-Pr2NEt systems (Entry 2, 3) afforded benzyl ac-
etate in high yield in short time. DMAP itself, under auxiliary base- and
solvent-free conditions, catalyzed the reaction to produce acylation prod-
uct in 91% yield after 24 h (Entry 6). This might be attributed to the
higher concentration, which leads to a polar reaction system [29,30]. It
was found that 10 mol% catalyst loading is enough to promote the acyla-
tion at room temperature in neat condition without Et3N (Entry 7, 8) [31].
Attempts were made to recycle the catalyst. When the reaction was
finished, hexane was added to extract the organic compounds. Based on
Acknowledgment
The authors gratefully acknowledge the financial support of the pro-
ject of “NUST Excellence Initiative”, Jiangsu Provincial Natural Science
Foundation of China for Key Projects (BK2010070) and Fundamental
Research Funds for the Central Universities (30920130111002).
Table 1
Acylation of benzyl alcohol with acetic anhydride.a
Entry
Catalyst
Time (h)
Yield (%)b
1
2
–
32
1
4
10 mol% DMAP,
100 mol% Et3N
10 mol% DMAP,
100 mol% i-Pr2NEt
20 mol% DMAP
20 mol% DMAP
20 mol% DMAP
10 mol% 3a
99 (92)
3
1
98
4
5
6
7
8
2
8
24
24
24
56
85
91 (84)
95, 93, 90
98 (91), 97, 94
10 mol% 3b
a
The reaction condition: benzyl alcohol, 1 mmol; acetic anhydride, 1.1 mmol.
GC yield based on benzyl alcohol. Numbers in parentheses are isolated yields.
b

28
W.-B. Yi et al. / Catalysis Communications 41 (2013) 26–28
O
O
O
H
H
+
C
2O
rt,neat
H
C
3
O
H
3C
H
C
3
O
Fluorous DMAP
precipitation recovery
recovery yield: 93%
purity: 99%
1s 98% yield
t
:
:
:
2n 97% yield
d
r
3 d 94% yield
Fig. 1. Recycle of fluorous DMAP iodide salt in the acylation.
Table 2
Acylation of alcohols with acid anhydrides.a
Entry
R1
R2
Yield (%)b
1
2
3
4
5
6
7
8
PhCH2
i-Pr
Me
i-Pr
Me
i-Pr
Me
i-Pr
Me
Me
Me
i-Pr
94 (89)
96 (88)
93 (85)
99 (93)
92 (86)
99 (92)
96 (87)
92 (84)
95 (87)
92 (81)
96 (89)
4-CH3-PhCH2
4-CH3-PhCH2
4-NO2-PhCH2
4-NO2-PhCH2
CH3(CH2)3
CH3(CH2)3
CH3(CH2)7
i-Pr
9
10
11
(CH2)6
(CH2)6
a
The reaction condition: alcohol, 1 mmol; acid anhydride, 1.1 mmol.
GC yield based on benzyl alcohol. Numbers in parentheses are isolated yields.
b
[24] L.V. Ding, J.A. Gladysz, Angewandte Chemie 44 (2005) 4095–4097.
[25] In: J.A. Gladysz, D.P. Curran, I.T. Horváth (Eds.), Handbook of Fluorous Chemistry,
Wiley-VCH, Weinheim, 2004.
[26] J. Legros, B. Crousse, D. Bonnet-Delpon, Journal of Fluorine Chemistry 129 (2008)
974–977.
[27] D. Vuluga, J. Legros, B. Crousse, D. Bonnet-Delpon, Chemistry – A European Journal
16 (2010) 1776–1779.
[28] Typical procedure for the preparation of fluorous DMAP 3b: The DMAP (1.22 g,
10 mmol) was slowly added to a solution of Rf8CH2CH2I (5.74 g, 10 mmol) in
CH2Cl2. After being stirred for 12 h, the mixture was concentrated and then
washed with n-hexane. After filtration, product was dried in vacuo at 50 °C for
8 h to give yellowlish solid (6.47 g, 93%). Melting point: 154–156 °C, 1H NMR
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