A succinimide-N-sulfonic acid catalyst for acetylation reactions in absence of a solvent

Article abstract of DOI:10.1016/S1872-2067(11)60499-3

A small amount of succinimide-N-sulfonic acid efficiently catalyzed the acetylation of a variety alcohols, phenols, thiols, amines and aldehydes with acetic anhydride at room temperature under solvent free conditions. This catalyst has the advantages of excellent yields and short reaction times and the reaction can be carried out on a large scale, which makes it potentially useful for industrial applications.

Full text of DOI:10.1016/S1872-2067(11)60499-3

Chinese Journal of Catalysis 34 (2013) 695–703
ava i l a b l e a t w w w. s c i e n c ed i r e c t . c o m
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e /c h n j c
Article
A succinimide‐N‐sulfonic acid catalyst for acetylation reactions in
absence of a solvent
Farhad SHIRINI*, Nader Ghaffari KHALIGH
Department of Chemistry, Faculty of Sciences, University of Guilan, Rasht, zip code 41335, Post box 1914, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
A small amount of succinimide‐N‐sulfonic acid efficiently catalyzed the acetylation of a variety al‐
cohols, phenols, thiols, amines and aldehydes with acetic anhydride at room temperature under
solvent free conditions. This catalyst has the advantages of excellent yields and short reaction times
and the reaction can be carried out on a large scale, which makes it potentially useful for industrial
applications.
Received 31 August 2012
Accepted 7 December 2012
Published 20 April 2013
© 2013, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Succinimde‐N‐sulfonic acid
Protection
Acetylation
Chemoselective reaction
Solvent‐free condition
1. Introduction
suffer from some disadvantages such as high temperature and
drastic reaction conditions, formation of undesirable or toxic
The protection of alcohols, phenols, thiols, and amines by
the formation of esters and amides is one of the most important
and widely used transformations in organic chemistry [1], es‐
pecially with polyfunctional molecules such as nucleosides,
carbohydrates, steroids, and natural products [2, 3].A variety of
procedures are routinely used for the preparation of acetyl
derivatives using homogeneous or heterogeneous catalysts
such as 4‐dimethylaminopyridine (DMAP) and 4‐pyrolidino‐
pyridine [4], tetramethylethylenediamine (TMEDA) [5], Bu3P
[6], iodine [7],p‐toluenesulfonic acid [8], alumina [9], zinc chlo‐
ride [10], cobalt chloride [11], montmorillonit K‐10 and KSF
[12], zeolite HSZ‐360 [13], zirconium sulfophenyl phosphonate
[15], Sc(OTf)3 [15], TaCl5 [16], trimethylsilyl trifluoro‐
methanesulfonate (TMSOTf) [17], Cu(OTf)2 [18], In(OTf)3 [19],
magnesium bromide [20], bismuth(III) salts [21], ferric per‐
chlorate adsorbed on silica‐gel [22], RuCl3 [23], InCl3 [24],
Ce(OTf)3 [25], Mg(ClO4)2 [26], ZrCl4 [27], Cp2ZrCl2 [28], and
cerium polyoxometalate [29]. However, each of these methods
byproducts, expensive reagents, the reagents are hygroscopic
or thermally unstable, use of halogenated solvents and strong
acids, long reaction times or low yields of the desired products,
and in most cases are only applicable to alcohols. Therefore, a
new method and catalyst for the preparation of esters and am‐
ides is still in demand.
Acylals (1,1‐diacetates) are remarkably stable derivatives of
aldehydes that are widely used for the protection of com‐
pounds. They also have many applications in organic synthesis
and industry. 1,1‐Diacetates are useful precursors in asymmet‐
ric allylic alkylation [30], synthesis of natural products [31],
and synthesis of 1‐acetoxy dienes and 2,2‐dichlorovinyl ace‐
tates for Diels‐Alder reactions [32,33]. In addition, the acylal
functionality can be converted to other functional groups by
reaction with the appropriate nucleophiles [34,35]. In addition,
1,1‐diacetates are used as cross‐linking agents for the cellulose
in cotton and as bleaching initiators in wine‐stained fabrics
[36,37]. Hence, methods for their synthesis have received con‐
*Corresponding author. Tel/Fax: +98‐131‐3233262; E‐mail: shirini@guilan.ac.ir
DOI: 10.1016/S1872‐2067(11)60499‐3 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 34, No. 4, April 2013

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
siderable attention.
NMR, and GCMS) as a standard sample of the acetylated prod‐
uct. The recovered catalyst was dried at 50 °C under vacuum
for 2 h and reused for four more acetylation reactions of benzyl
alcohol (1.0 mmol) affording 98%, 97%, 97%, and 96% yields,
respectively, in 2, 3, 3, and 5 min.
Usually the preparation of 1,1‐diacetates are carried out by
the reaction of aldehydes with acetic anhydride using catalysts
such as H2SO4 [38], H3PO4 and CH3SO3H [33], NH2SO3H [39],
HClO4‐SiO4 [40], Zr(HSO4)4 [41], saccharin sulfonic acid [42],
[Hmim]HSO4 [43], p‐toluenesulfonic acid (p‐TSA) [44], sili‐
ca‐bonded S‐sulfonic acid [45], silicasuloric acid [46], copper
methanesulfonate‐HOAc [47], 1,3‐dibromo‐5,5‐ dimethylhy‐
dantoin [48], ZnCl2 [49], FeCl3 [50], PCl3 [51], InCl3 [52], cy‐
anuric chloride [53], ceric ammonium nitrate (CAN) [54], NBS
[55], WCl6 [56], SbCl3 [57, 58], ZrCl4 [59], LiClO4 [60], Sc(OTf)3
[61], Cu(OTf)2 [62], Bi(OTf)3 [63], LiOTf, [64], In(OTf)3 [65],
montmorillonite clay [66], expansive graphite [67], H3PMo12O40
[68], H6P2W1O62∙24H2O [69], AlPW12O40 [70], zirconium sul‐
fophenyl phosphonate [71] or Bi(NO3)3·5H2O [72]. Although
some of these catalysts can convert aldehydes to the corre‐
sponding diacetates with good to high yields, the majority suf‐
fer from at least one disadvantages such as prolonged reaction
times, reaction under oxidizing conditions, use of a strong acid,
low yields, harsh reaction conditions, difficulty in the prepara‐
tion, moisture sensitivity of the reagent used, or high cost and
high toxicity of the reagent used. Therefore, there is scope for
developing an alternative method for the protection of alde‐
hydes as acylals.
2.3. Acetylation of alcohols, phenols, thiols, and amines with
different substrates
A mixture of 1 mmol substrate, 2–3 mmol acetic anhydride,
and 5 mg SuSA (0.028 mmol) was stirred at room temperature
in the absence of a solvent. The progress of the reaction was
monitored by TLC. After completion of the reaction, the mixture
was diluted with 15 ml ethyl acetate and filtered. Then the solid
residue was washed with 5 ml ethyl acetate, then 5 mlacetone
and then dried. The recovered catalyst could be used for three
more reaction runs. The organic layer was washed with 5 ml of
a saturated solution of NaHCO3, 20 ml brine and 20 ml water,
and dried over MgSO4. Evaporation of the solvent followed by
column chromatography on silica gel followed by evaporation
of the solvent gave the desired product in good to high yields.
2.4. Spectral data of the selected products
1
A (Table 2, entry 14): IR (neat, cm–1) 1738, 1697. H NMR
2. Experimental
(CDCl3, 400 MHz): δ 2.23 (s, 3H), 6.84 (s, 1H), 7.32–7.53 (m,
8H), 7.95 (d, J = 8.8 Hz, 2H). 13C NMR (CDCl3,100 MHz): δ 20.1,
77.2, 128.2, 128.3, 128.6, 128.8, 133.1, 133.1, 134.1, 169.9,
193.3.
2.1. General
All chemicals were purchased from Merck or Fluka Chemi‐
cal Companies. All yields refer to the isolated products. Prod‐
ucts were characterized by their physical constants and com‐
parison with standard samples. The determination of the purity
of the substrates and reaction monitoring were performed by
TLC using silica gel SIL G/UV 254 plates. The MS were meas‐
ured under 70 eV conditions. The IR spectra were recorded on
B (Table 2, entry 16): IR (neat, cm–1) 1726; [α]25 = –38°
(neat). H NMR (CDCl3, 400 MHz): δ 0.82 (s, 3H), 0.88 (s, 3H),
1
0.92 (s, 3H), 1.26 (m, 4H), 1.72 (m, 2H), 2.08 (s, 3H), 2.36 (m,
1H), 4.89 (d, J = 9.8 Hz, 1H). 13C (CDCl3,100 MHz): δ 13.4, 18.7,
19.6, 21.2, 27.0, 28.0, 36.7, 44.8, 47.7, 48.6, 79.8, 171.3.
C (Table 2, entry 19): mp 70–72 °C; IR (KBr, cm–1) 1756. 1H
NMR (CDCl3, 400 MHz): δ 2.38 (s, 3H), 7.25 (d, J = 8.8 Hz, 1H),
7.46 (m, 2H), 7.55 (s, 1H), 7.79 (m, 3H). 13C NMR (CDCl3, 100
MHz): δ 21.2, 118.5, 121.1, 125.7, 126.5, 127.6, 127.7, 129.4,
131.4, 133.7,148.3, 169.6.
1
a Perkin Elmer 781 spectrophotometer. The H NMR spectra
were recorded with a Bruker Avance 400 or 300 MHz instru‐
ment. Chemical shifts are reported in parts per million in CDCl3
with tetramethylsilane as an internal standard. 13C NMR data
were collected on a Bruker Avance 100 or 75 MHz instrument.
Melting points were recorded on a Büchi B‐545 apparatus with
open capillary tubes.
D (Table 2, entry 23): IR (neat, cm–1) 1768. 1H NMR (CDCl3,
400 MHz): δ 2.31 (s, 6H), 2.31 (s, 3H), 7.14 (d, J = 8.0 Hz, 2H),
7.28 (dd, J = 8.8 and 7.6 Hz, 1H). 13C NMR (CDCl3,100 MHz): δ
20.2, 20.7, 120.7, 125.9, 134.7, 143.6, 167.0, 167.9.
1
E (Table 2, entry 28): IR (neat, cm–1) 3295, 1635. H NMR
2.2. Acetylation of alcohols, phenols, thiols, and amines with
different amounts of succinimide N‐sulfonic acid
(CDCl3): δ 2.30 (s, 3H), 7.45–7.87 (m, 8H). 13C NMR (CDCl3,100
MHz): δ 22.8, 118.5, 122.3, 122.8, 125.2, 126.1, 127.3, 127.8,
128.4, 128.5, 133.1, 169.9.
1
The substrate (1.0 mmol) was treated with Ac2O (1.5–2
mmol) in the presence of succinimide N‐sulfonic acid (SuSA,
0.028 mmol) at room temperature under solvent free condi‐
tions and with magnetic stirring. After the completion of the
reaction as indicated by TLC, the mixture was diluted with Et2O
(25 ml) and the catalyst was allowed to settle down. The su‐
pernatant ethereal solution was decanted off, the catalyst
washed with Et2O (2 ml) and the combined ethereal solution
was concentrated under vacuum to afford the product. The
product had identical physical properties (mp, IR, 1H and 13C
F (Table 2, entry 31): IR (neat, cm–1) 1743, 1653. H NMR
(CDCl3, 400 MHz): δ 1.97 (s, 3H), 2.02 (s, 3H), 2.11 (s, 3H), 2.20
(s, 3H), 3.47 (t, J = 6.0 Hz, 2H), 3.61 (t, J = 5.6 Hz, 2H), 4.11 (t, J =
6.0 Hz, 2H), 4.19 (t, J = 5.6 Hz, 2H), 4.59 (s, 2H), 4.62 (s, 2H),
7.14–7.36 (m, 10H). 13C NMR (CDCl3, 100 MHz): δ 20.7, 20.8,
21.5, 21.6, 45.0, 46.1, 48.2, 53.1, 61.2, 62.2, 126.2, 127.5, 127.7,
127.9, 128.6, 128.9, 136.6, 137.2, 170.5, 170.8, 171.1, 171.5.
For this product (entry 31), a series of molecular ab initio
calculations were carried out to understand the 1H and 13C
NMR spectra of 2‐(N‐benzylacetamido)ethyl acetate. Calcula‐

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
tions were performed with the Gaussian 98 set of programs
O
O
[73] on a personal computer (Pentium 4). Geometry optimiza‐
tion were done both at the Hartree‐Fock level with analytic
gradients and with the 6‐31G* basis set. The results demon‐
strated that the product can exist in many conformations, and
two conformations (I) and (II) were identified that had the
lowest energy conformation. Figure 1 shows the result of rota‐
tion around the bond connecting the C1–C2–N3–C4 atoms. The
conformational heterogeneity of this product and the high in‐
ter‐conversion barriers are due to the high steric demand of the
acetamide group with the ortho‐position hydrogen atoms of
the phenyl ring.
CH2Cl2, ClSO3H
+
HCl
NH
N
SO3H
Solvent free, Ice bath-r.t.
O
O
SuSA
Scheme 1. Preparation of SuSA.
Ac2O, SuSA
X = O, S and N
R = Alkyl and Aryl
R-XH
R-XAc
Solvent free, rt
Scheme 2. Acetylation of alcohols, phenols, thiols, and amines catalyzed
by SuSA.
G (Table 2, entry 32): IR (neat, cm–1) 3320, 1730, 1682. 1H
NMR (CDCl3, 400 MHz): δ 2.16 (s, 3H), 2.36 (s, 3H), 7.14–7.17
(m, 2H), 7.22–7.25 (m, 1H), 7.39 (br s, 1H), 8.11 (d, J = 7.6 Hz,
1H). 13C NMR (CDCl3, 100 MHz): δ 20.6, 22.7, 117.8, 120.7,
123.9, 125.9, 130.7, 140.5, 167.0, 167.9.
L (Table 5, entry 24): white solid, mp 96–98 C. IR (KBr,
cm–1): 3002, 2920, 1752, 1430, 1362, 1340, 1240, 1200, 1158,
1106, 1060, 1000, 942, 910, 808, 710, 680, 650, 600, 530, 510.
1H NMR (300 MHz, DMSO): δ 2.10 (s, 12H, 4× COCH3), 7.52 (d,
1H, J = 7.8 Hz, ArH), 8.00 (d, 1H, J = 7.9 Hz, ArH), 8.17 (s, 1H,
CH(OAc)2). 8.43 (dd, 2H, J = 7.6, J = 8.2 Hz, ArH). 13C NMR (75
MHz, DMSO): δ 167.00, 141.19, 129.62, 128.82, 126.32, 102.33,
22.55.
M (Table 5, entry 15): white solid, mp 164–166 C. IR (KBr,
cm–1): 3020, 2910, 1758, 1430, 1378, 1338, 1200, 1118, 1060,
1008, 960, 940, 910, 852, 818, 604, 580, 540. H NMR (300
MHz, CDCl3): δ 2.37 (s, 6H, 2 × COCH3), 7.29 (d, 1H, J = 5.7 Hz,
ArH), 7.41 (d, 1H, J = 5.1 Hz, ArH), 8.26 (s, 1H, CH(OAc)2). 13C
NMR (75 MHz, DMSO): δ 167.00, 141.19, 129.82, 104.33, 21.55.
1
H (Table 2, entry 35): IR (neat, cm–1) 1765, 1679. H NMR
(CDCl3, 400 MHz): δ 2.33 (s, 3H), 2.45 (s, 3H), 7.24 (d, J = 8.0 Hz,
1H), 7.33 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H) 7.53 (d, J = 7.6
Hz, 1H). 13C NMR (CDCl3,100 MHz): δ 20.7, 26.2, 120.7, 125.9,
130.2, 134.7, 143.5, 167.0, 171.9.
I (Table 2, entry 36): IR (neat, cm–1) 1696. 1H NMR (CDCl3,
400 MHz): δ 2.36 (s, 3H), 4.29 (s, 2H), 6.01 (d, J =2.8 Hz, 1H),
6.23 (dd, J = 2.8 and 0.8 Hz, 1H), 7.22 (d, J = 0.8, 1H). 13C NMR
(CDCl3,100 MHz): δ 22.4, 29.7, 107.2, 110.7, 141.7, 152.7, 194.3.
J (Table 5, entry 10): white solid, mp 65–67 C. IR (KBr,
cm–1): 3650, 3500, 3010, 2910, 1760, 1610, 1590, 1490, 1430,
1370, 1245, 1200, 1160, 1060, 1010, 970, 940, 917, 790, 760,
1
1
700, 670, 600. H NMR (300 MHz, DMSO): δ 2.13 (s, 6H, 2×
3. Results and discussion
COCH3), 3.38 (s, 3H, CH3), 7.02 (d, 1H, J = 7.9 Hz, ArH), 7.50 (d,
1H, J = 7.9 Hz, ArH), 7.60–7.66 (m, 2H, J = 8.3, J = 7.7 Hz, ArH),
8.04 (s, 1H, CH(OAc)2). 13C NMR (75 MHz, DMSO): δ 167.55,
147.74, 135.42, 133.82, 127.94, 125.12, 123.53, 87.83, 21.93,
21.00.
K (Table 5, entry 15): white solid, mp 72–74 C. IR (neat,
cm–1): 3035, 2985, 1760, 1610, 1595, 1530, 1465, 1370, 1310,
1245, 1210, 1170, 1100, 995, 970, 840, 760. 1H NMR (300 MHz,
CDCl3): δ 2.10 (s, 6H, 2× COCH3), 3.06 (s, 3H, CH3), 3.89 (s, 3H,
CH3), 6.81 (d, 1H, J = 4.9 Hz, ArH), 6.88 (dd, 1H, J = 4.9, J = 1.1
Hz, ArH), 6.98 (d, 1H, J = 1.1 Hz, ArH), 7.97 (s, 1H, CH(OAc)2).
13C NMR (75 MHz, DMSO): δ 167.55, 149.823, 148.37, 147.74,
123.53, 113.43, 113.32, 87.84, 55.66, 54.55, 23.30.
Recently, we reported the preparation of succin‐
imide‐N‐sulfonic acid (SuSA) (Scheme 1) and its application to
the trimethylsilylation of hydroxyl groups and deprotection of
the obtained trimethylsilyl ethers[74] and N‐Boc protection of
amines [75].
In a continuation of these studies, we investigated the ap‐
plicability of this reagent as the catalyst for other organic func‐
tional group transformations. Our investigations clarified that
SuSA can efficiently catalyze the acetylation of alcohols, phe‐
nols, amines, and thiols with Ac2O in the absence of a solvent
(Scheme 2).
12000
10000
8000
6000
4000
2000
0
(c)
(b)
(a)
0
50 100150200250300350400450
Torsional angle
Fig. 1. Conformational energy (kJ/mol) for the lowest energy conformation of acetic acid 2‐(acetyl‐benzyl‐amino)‐ethyl ester as a function of rota‐
tion around the C1–C2–N3–C4 bond.

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
Table 1
100
Reaction of benzyl alcohol and Ac2O in the presence of different
amounts of SuSA at room temperature under solvent free conditions.
80
60
40
20
0
Entry
Amount of SuSA (mol%)
Time (min)
Yield a (%)
1
2
3
4
5
6
7
—
1.1
2.2
2.8
3.3
4.4
10
720
5
2
2
2
N.R.
76
82
98
98
98
99
2
2
1
2
3
Run
4
5
Reaction conditions:1.0 mmol substrate, 1.5 equiv Ac2O.
a Determined by GC‐MS of the corresponding acetylated products.
Fig. 2. Recovery and reuse of the catalyst for the acetylation of benzyl‐
alcohol with Ac2O at room temperature under solvent free conditions.
In order to optimize the reaction conditions, different
amounts of succinimide‐N‐sulfonic acid (SuSA) were used to
make benzyl acetate from benzyl alcohol and acetic anhydride
at room temperature under solvent free conditions. The results
are summarized in Table 1. The reaction can be carried out in
the presence of small catalytic amounts of SuSA in the absence
of a solvent, and the yields were excellent. It should be noted
that when the reaction used a solvent, the reaction time be‐
came longer or the reaction did not proceed at all. The reaction
did not occur in the absence of the catalyst (Table 1, entry 1).
After these preliminary experiments, a small catalytic
amount of SuSA (2.8 mol%) was used to convert a variety of
functionalized alcohols and phenols with acetic anhydride into
the corresponding esters and amides at room temperature
under solvent free conditions. As shown in Table 2, different
types of benzylic (including those with electron donating or
withdrawing groups) and aliphatic alcohols underwent acety‐
lation with Ac2O (1.5–2.0 equiv) in the presence of catalytic
amounts of SuSA in the absence of a solvent at room tempera‐
ture in good to high yields. The reaction conditions were mild
enough not to induce any damage to moieties like the methoxy
group (Table 2, entry 8), which often undergoes cleavage in the
presence of strong acids or some Lewis acids. With sterically
hindered alcohols, excellent chemoselectivity was observed as
these compounds did not show any competitive dehydration
(Table 2, entries 9–16). In order to show the mildness and ste‐
reospecificity of the SuSA catalyzed acetylation of alcohols, the
reactions of optically active L(–)‐menthol and R(+)‐borneol
were studied (Table 2, entries 12 and 16). We observed that
L(–)‐menthol ([α]D = –49.0o, c = 10 in 95% ethanol, 99% ee)
and R(+)‐Borneol ([α]D = +37.9o, c = 5 in ethanol, 99% ee) re‐
acted enantioselectively with the retention of the configuration
on the benzylic center to provide L‐(–)‐Menthyl acetate ([α]D =
–73.0o, neat, 98% ee) and (+)‐Bornyl acetate ([α]D = +41.5o,
neat, 96% ee). The highest optical purity was obtained as an
optically pure form in high yield and high regioselectivity by
using SuSA at room temperature under solvent free conditions.
The optical rotation of the product was determined and com‐
pared with that reported by Aldrich.
O
O
O
X = O, S, and N
R = Alkyl and Aryl
O
O
O
O
N
SO3H
O
S O H
N
H
O
O
X
O
O
(I)
R
O
R
X
H
O
N
SO3
RXAc
HOAc
O
Scheme 3. Proposed mechanism of the acetylation of alcohols, phenols,
thiols, and amines.
acetylated with the reaction conditions (Table 2, entries 20–23,
29–32, and 35) and furyl mercaptane was transformed
smoothly to the corresponding acetate derivative (Table 2,
entry 36).
SuSA was a reusable catalyst and after five runs of the acet‐
ylation of benzyl alcohol with acetic anhydride, the catalytic
activity of SuSA was almost the same as that of the fresh cata‐
Table 3
Superiority of SuSA catalyst for the acetylation of benzylalcohol over
some recently reported catalysts at room temperature under solvent
free conditions.
Amount of catalyst Time Yield a
Entry
Catalyst
Ref.
(mol%)
10
(min)
1
(%)
99
1
2
I2
CoCl2
[7]
[11]
0.5
240
98
montmorillonit
KSF
3
20 mg
60
90
[12]
4
5
6
7
8
9
10
11
zeolite HSZ‐360
Cu(OTf)2
RuCl3
20 mg
2
5
0.1
1
1
1
60
30
60
30
12
15
600
2
84
97
96
85
98
[13]
[18]
[23]
[24]
[25]
[26]
[28]
InCl3
Ce(OTf)3
Mg(ClO4)2
Cp2ZrCl2
SuSA
100
93
98 this work
Our investigations showed that under the same reaction
conditions, SuSA catalyzed the acetylation of phenols, amines,
and thiols in good to high yields (Table 2, entries 17–36). Our
protocol has the advantages that two or three groups were
2.8 (5 mg)
a Isolated yield.
b Temperature 60 oC.

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
Table 2
SuSA catalyzed acetylation of alcohols, phenols, thiols, and amines with Ac2O at room temperature under solvent‐free conditions.
Time Yield
Time Yield
Entry
Substrate
Product
Entry
Substrate
Product
(min)
(%)
(min)
(%)
CH2OAc
OH
OAc
CH2OH
1
2
98
19
10
90
OH
OAc
CH2OH
CH2OAc
OH
OAc
2
2
96
20
30
84 b
CH3
CH3
CH2OH
CH2OAc
3
4
2
2
95
94
21
22
20
2
87 b
93 b
HO
OH
AcO
OAc
Cl
CH2OH
Cl
CH2OAc
OH
OAc
HO
AcO
Br
Br
OH
OAc
CH2OH
CH2OAc
OH
OAc
5
30
88
23
35
92 c
NO2
NO2
OH
OAc
NH2
NH2
NHAc
NHAc
6
7
35
2
83
94
24
25
2
1
90
96
O2N
Cl
CH2OH
O2N
Cl
CH2OAc
CH2OH
CH2OAc
CH2OAc
CH3
CH3
H3CO
CH2OH
H3CO
NH
NHAc
Br
Br
8
9
5
4
95
92
26
27
2
1
86
93
2
OH
OAc
O N
NH
O N
2
NHAc
NHAc
2
2
NH2
OH
OAc
OAc
10
4
92
28
2
90
OH
OH
11
12
4
94
86
29
30
10
4
93 b
98b
OH
CH2OH
CH2OAc
HO
AcO
OH
OH
H C
H C
3
3
15
CH
3
CH
3
CH2OH
CH2OAc
H C
3
H C
3
OH
OAc
OAc
OH
N
N
H
13
14
15
8
88
96
89
31
32
33
10
2
98 b
98b
92
Ac
O
O
OH
OAc
10
10
NH2
NHAc
SAc
OH
OAc
SH
10
OH
CH3
CH3
OAc
CH3
H3C
HO
H3C
AcO
CH3
CH SH
2
CH SAc
2
16
17
18
8
95
94
90
34
35
36
8
93
90
84
OH
SH
OH
OH
OH
OAc
OAc
10
15
20
12
SAc
CH2SH
CH2SAc
O
O
a Isolated yield of acetylated product.
b Isolated yield of di‐acetate.
c Isolated yield of tri‐acetate.
lyst (Fig. 2).
hydride is first activated by SuSA to afford (I). Alcohol, phenol,
amine or thiol attacks I which in turn is converted to the final
product and releases SuSA for the next catalytic cycle (Scheme
3).
The selectivity of this reaction system was checked with the
competitive acetylation of benzyl alcohol, phenol, aniline, and
thiophenol together. The results showed that aniline was acet‐
To illustrate the efficiency of this catalyst, we compare the
results of the acetylation of benzyl alcohol with acetic anhy‐
dride catalyzed by SuSA with some results reported in the lit‐
erature (Table 3). It is clear that our reaction system is superior
in terms of reaction time, catalyst amount, and product yield.
The probable mechanism is shown in Scheme 3. Acetic an‐

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
Table 4
Competitive acetylation of benzyl alcohol, phenol, thiophenol and aniline catalyzed by NSPVPC.
Entry
1
Substrate
Product
Time (min)
5
Yield a (%)
100 + 0
NH2
NHAc
SH
SAc
+
+
NH2
NHAc
CH2OH
CH2OH
OAc
OH
OAc
+
2
3
4
5
+
+
5
5
100 + 0
88 + 12
+
CH2OH
OH
OAc
+
+
CH2OH
SH
SAc
SAc
+
10
10
85.6 + 14.4
64 + 36
+
OH
SH
Reaction conditions: 1.0 mmolsubstrate, 1.5 equiv Ac2O, 5 mg (0.028 mmol) catalyst.
a Determined by GC‐MS of the acetylated products.
ylated selectively in the presence of benzyl alcohol, phenol, and
thiophenol (Table 4, entries 1 and 2). This can be considered as
a useful practical achievement in the acetylation of amines in
the presence of alcohols, phenols and thiols. Also, benzyl alco‐
hol was acetylated selectively in the presence of phenol and
thiophenol in 88%:12% and 85.6%:14.4% yields, respectively
(Table 4, entries 3 and 4). Phenol was acetylated in the pres‐
ence of thiophenol in 64:36% yield (Table 4, entry 5).
Ac2O, SuSA
RCHO
RCH(OAc)2
Solvent free, rt
Scheme 4. Acetylation of aldehydes.
O
O
OH
O3S
N
N
SO3H + RCHO
R
H
O
O
(SuSA)
O
O
Notably, the conversion of 4‐chlorobenzyl alcohol to the ac‐
etate product can be carried out on a larger scale (10 mmol)
O
Intermolecular
O
O
Intramolecular
with 92% yield in 10 min by using 5 mg (0.028 mmol) of SuSA.
O
H
This indicates that a large scale reaction is possible with the
same amount of the catalyst. It is important to point out that
the present reaction system is clean, and does not need a
chromatographic separation.
O
O
H
R
O
OAc
OAc
O
R
O
R
O3S
N
O
O
O
O
O
O
O3S
N
O
After the above study, we found that SuSA also efficiently
catalyzed the conversion of aldehydes to their corresponding
1,1‐diacetates with acetic anhydride (Scheme 4). The results
Scheme 5. Proposed mechanism of the acetylation of aldehydes.
formed under strongly acidic conditions (Table 5, entry 19).
The catalyst is also very useful for the protection of aliphatic
and α,β‐unsaturated aldehydes (Table 5, entries 20–22). No
isomerisation of conjugated aldehydes was observed in the
presence of SuSA. The acetylation of phthalaldehyde gave the
diacetylated product in good yield (85%) accompanied by a
minor amount (12%) of the tetraacylated product (Table 5,
entry 23). For iso‐phthalaldehyde and tere‐phethalaldehyde,
the tetra‐acylated products were obtained in high yields (Table
are tabulated in Table 5.
As shown in Table 5, different types of aromatic aldehydes
with different substituents such as NO2, Cl, Br, CN, Me, and MeO
were converted to their corresponding acylals in good to high
yields (Table 5, entries 1–15). In hydroxyl containing aromatic
aldehydes, the phenol –OH groups were also acylated in high
yields (Table 5, entries 16–18). Using this catalyst, furfural as
an acid sensitive substrate was also protected in high yield and
without the formation of any side products, which are normally
Table 6
Comparison of different catalysts in gem‐diacetate synthesis from benzaldehyde and cinnamaldehyde.
Entry
Catalyst
succinimide sulfonic acid
saccharin sulfonic acid
p‐TSA
Time (min)/Yield (%) a
12/98
Time (min)/Yield (%) b
5/93
Ref.
this work
[14]
[16]
[18]
[19]
[20]
[27]
[15]
1
2
3
4
5
6
7
8
9
10
48/90
25/96
30/84
78/94
90/98
720/95
25/90
12/84
90/87
—
35/92
15/81
120/67
48/92
1200/48
10/95
180/72
720/82
silica sulfuric acid
copper methanesulfonate‐HOAc
1,3‐dibromo‐5,5‐dimethyl hydantoin
NBS
[Hmim]HSO4
zirconium sulfophenyl phosphonate
Bi(NO3)3∙5H2O
[43]
[44]
a Times and yields refer to gem‐diacetate synthesis from benzaldehyde.
b Times and yields refer to gem‐diacetate synthesis from cinnamaldehyde.

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
Table 5
Acylation of aldehydes and deprotection of the obtained acylals a,b
.
Entry
1
Substrate
Ph‐CHO
Product
Ph‐CH(OAc)2
Time (min)
Yield (%)
12
98
2
3
4
5
13
40
4
5
95
93
98
87
2‐NO2‐Ph‐CHO
3‐NO2‐Ph‐CHO
4‐NO2‐Ph‐CHO
2‐Cl‐Ph‐CHO
2‐NO2‐Ph‐CH(OAc)2
3‐NO2‐Ph‐CH(OAc)2
4‐NO2‐Ph‐CH(OAc)2
2‐Cl‐Ph‐CH(OAc)2
6
10 (12, 12, 20) c
88 (82, 76, 76) c
4‐Cl‐Ph‐CHO
4‐Cl‐Ph‐CH(OAc)2
7
8
9
42
45
55
4
86
92
72
88
94
86
91
88
86
88
80
88
2‐Br‐Ph‐CHO
4‐Br‐Ph‐CHO
4‐CN‐Ph‐CHO
2‐Me‐Ph‐CHO
4‐Me‐Ph‐CHO
2‐MeO‐Ph‐CHO
3‐MeO‐Ph‐CHO
4‐MeO‐Ph‐CHO
3,4‐(MeO)2‐Ph‐CHO
2‐HO‐Ph‐CHO
3‐HO‐Ph‐CHO
4‐HO‐Ph‐CHO
2‐Br‐Ph‐CH(OAc)2
4‐Br‐Ph‐CH(OAc)2
4‐CN‐Ph‐CH(OAc)2
2‐Me‐Ph‐CH(OAc)2
4‐Me‐Ph‐CH(OAc)2
2‐MeO‐Ph‐CH(OAc)2
3‐MeO‐Ph‐CH(OAc)2
4‐MeO‐Ph‐CH(OAc)2
3,4‐(MeO)2‐Ph‐CH(OAc)2
2‐(OAc)‐Ph‐CH(OAc)2
3‐(OAc)‐Ph‐CH(OAc)2
4‐(OAc)‐Ph‐CH(OAc)2
10
11
12
13
14
15
16
17
18
2
82
49
64
42
20
32
24
19
42
94
CH(OAc)
CHO
O
2
O
20
21
22
31
64
5
85
96
93
Ph‐CH2CHO
Me(CH2)4CHO
Ph‐CH=CHOCHO
Ph‐CH2CH(OAc)2
Me(CH2)4CH(OAc)2
Ph‐CH=CHOCH(OAc)2
CH(OAc)
CH(OAc)
CH(OAc)
2
2
CHO
12d
85 + 12
+
23
24
CHO
2
CHO
5 d
4 d
87
96
(AcO)2HC
(AcO)2HC
CH(OAc)2
CH(OAc)2
CHO
CHO
OHC
OHC
25
26
H
N
H
N
720
720
0 e
0 e
CHO
CH(OAc)2
NMe2
Me2N
MeOC
OHC
OHC
CH(OAc)2
CH(OAc)2
27
COMe
47
10
92
28
29
100 f + 0 e
4‐Cl‐Ph‐CHO + Ph‐COMe
4‐Cl‐Ph‐CH(OAc)2 + Ph‐C(OAc)2Me
a Products were characterized by their physical properties and IR and NMR spectroscopy.
b Isolated yield. c Results using recycled catalyst. d 3 mmol of acetic anhydride was used. e Starting material recovered intact. f Conversion.
5, entries 24 and 25). However, 4‐(dimethylamino) benzalde‐
hyde and indole‐3‐carbaldehyde failed to give the correspond‐
ing 1,1‐diacetates under the same conditions, which may be
due to the electron donation ability of the dimethylamino and
NH groups (Table 5, entries 26 and 27).
To evaluate the chemoselectivity of the catalyst, the com‐
petitive reactions for the acylation of aldehydes in the presence
of ketones using SuSA as catalyst was also investigated. A high‐
ly selective conversion of aldehydes in the presence of ketones
was observed (Table 5, entries 28 and 29).
SuSA can be effectively recovered from the reaction mixture
during the work‐up procedure (Table 5, entry 6). The percent
of recovery in most cases was more than 80% and there was no
change in the catalytic activity of SuSA.
As outlined in Scheme 5, the possible mechanism of this re‐
action may involve either intermolecular or intramolecular
transfer of the second acetate group after the initial attack by
acetic anhydride. The role of the catalyst here is the activation
of the carbonyl group for these nucleophilic attacks.
In order to show the merit of the present work, Table 6
compares the results obtained from the gem acylation of ben‐
zaldehyde and cinnamaldehyde by our reaction system with
some of those reported in the literature.
In addition to economic benefits, a successful recycling of a
catalyst will also lead to a cleaner process, because this will not
leave any catalyst contamination in the products. We found that

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
[28] Kantam M L, Aziz K, Likhar P R. Catal Commun, 2006, 7: 484
4. Conclusions
[29] Mirkhani V, Tangestani Nejad S, Moghaddam M, Yadollahi B,
Alipanah L. Monatsh Chem, 2004, 135: 1257
The acetylation of alcohols, phenols, thiols, amines, and al‐
dehydes with acetic anhydride are efficiently catalyzed by Su‐
SA, which is a newly prepared succinimide‐based reagent. High
yields, short reaction times, mildness of the reaction conditions,
ease of the preparation, stability and reusability of the reagent,
chemoselectivity and easy work‐up are the advantages of this
catalytic reaction system.
[30] Trost B M, Lee C. J Am Chem Soc, 2001, 123: 12191
[31] Sandberg M, Sydnes L K. Org Lett, 2000, 2: 687
[32] Held H, Renestle A, Mayer A. Ullman’s Encyclopedia of Industrial
Chemistry, 5th Ed, Vol. 1. Gerhartz W ed. New York: Wiley‐VCH,
1985
[33] Freeman F, Karchefski E M. J Chem Eng Data, 1977, 22: 355
[34] Van Heerden F R, Huyser J J, Bradley D, Williams G, Holzapfel C W.
Tetrahedron Lett, 1988, 39: 5281
Acknowledgements
[35] Sandberg M, Sydnes L K. Tetrahedron Lett, 1988, 39: 6361
[36] Jr Frick J G, Jr Harper R J. J Apll Polym Sci, 1984, 29: 1433
[37] Sanderson W R. EP Patent 0 125 781. 1984
[38] Wegscheider R, Spath E. Monatsh Chem, 1909, 30: 825
[39] Jin T S, Sun G, Li Y W, Li T S. Green Chem, 2002, 4: 255
[40] Kamble V T, Jamode V S, Joshi N S, Biradar A V, Deshmukh R Y.
Tetraherdon Lett, 2006, 47: 5573
We are thankful to the University of Guilan Research Council
for the partial support of this work.
References
[41] Mirjalili B F, Zolfigol M A, Bamoniri A, Sheikhan N. J Chin Chem Soc,
2006, 53: 955
[42] Shirini F, Mamaghani M, Mostashari‐Rad T, Abedini M. Bull Korean
Chem Soc, 2010, 31: 2399
[43] Hajipour A R, Khazdooz L, Ruoho A E. Catal Commun, 2008, 9: 89
[44] Manjula K, Pasha M A. Synth Commun, 2007, 37: 1563
[45] Niknam K, Saberi D, Nouri Sefat M. Tetrahedron Lett, 2009, 50:
4058
[46] Desai U V, Thopta T S, Pore D M, Wadgaonkar P P. Catal Commun,
2006, 7: 508
[1] Green T W, Wuts P G M. Protective Groups in Organic Synthesis.
New York: Wiley. 1999
[2] Sun X L, Kai T, Takayanagi H, Furuhata K. Synlett, 1999: 1399
[3] Yadav J S, Narsaiah A V, Basak A K, Goud, P R, Sreenu D K, Nagaiah
K. J Mol Catal A, 2006, 255: 78
[4] Scriven E F V. Chem Soc Rev, 1983, 12: 129
[5] Sano T, Ohashi K, Oriyama T. Synthesis, 1999: 1141
[6] Vedejs E, Bennett N S, Conn L M, Diver S T, Gingras M, Lin S, Oliver
P A, Peterson M J. J Org Chem, 1993, 58: 7286
[7] Phukan P. Tetrahedron Lett, 2004, 45: 4785
[8] Cope A C, Herrich E C. Organic Synthesis Collective, Vol. IV. New
York: Wiley, 1963. 304
[9] Breton G W, Kurtz M J, Kurtz S L. Tetrahedron Lett, 1997, 38: 3825
[10] Baker R H, Bordwell F G. Organic Synthesis Collective. Vol. III. New
York: Wiley, 1995. 141
[11] Iqbal J, Srivastava R R. J Org Chem, 1992, 57: 2001
[12] Hagiwara H, Morohashi K, Suzuki T, Ando M, Yamamoto I, Kato M.
Synth Commun, 1998, 28: 2001
[13] Ballini R, Bosica G, Carloni S, Ciaralli L, Maggi R, Sartori G.
Tetrahedron Lett, 1998, 39: 6049
[14] Curini M, Epifano F, Marcotullio M C, Rosati O, Rossi M. Synth
Commun, 2000, 30: 1319
[15] Ishihara K, Kubota M, Kurihara H, Yamamoto H. J Org Chem, 1996,
61: 4560
[16] Chandrasekhar S, Ramachander T, Takhi M. Tetrahedron Lett,
1998, 39: 3263
[17] Procopiou P A, Baugh S P D, Flack S S, Inglis G G A. J Org Chem,
1998, 63: 2342
[18] Saravanan P, Singh V K. Tetrahedron Lett, 1999, 40: 2611
[19] Chauhan K K, Frost C G, Love I, Waite D. Synlett, 1999: 1743
[20] Pansare S V, Malusare M G, Rai A N. Synth Commun, 2000, 30:
2587
[21] Mohammadpoor‐Baltork I, Aliyan H, Khosropour A R. Tetrahe‐
dron, 2001, 57: 5851
[22] Parmar A, Kaur J, Goyal R, Kumar B, Kumar H. Synth Commun,
1998, 28: 2821
[23] De S K. Tetrahedron Lett, 2004, 45: 2919
[24] Chakraborti A K, Gulhane R. Tetrahedron Lett, 2003, 44: 6749
[25] Dalpozzo R, Nino A D, Maiuolo L, Procopiou A, Nardi M, Bartoli G,
Romeo R. Tetrahedron Lett, 2003, 44: 5621
[26] Chakraborti A K, Sharma L, Gulhane R, Shivani. Tetrahedron, 2003,
59: 7661
[47] Wang M, Gong H, Jiang H, Wang Z. Synth Commun, 2006, 36: 1953
[48] Azarifar D, Ghasemnejad H, Ramzanian‐lehmali F. Mendeleev Co‐
muun, 2005, 15: 209
[49] Scriabine I. Bull Soc Chim Fr, 1961: 1194
[50] Wang C D, Li M H. Synth Commun, 2002, 32: 3469
[51] Michie J K, Miller J A. Synthesis, 1981: 824
[52] Yadav J S, Reddy B V S, Srinivas C. Synth Commun, 2002, 32: 1175
[53] Bandgar B P, Joshi N S, Kamble V T A. J Chin Chem Soc, 2007, 54:
489
[54] Roy S C, Banerjee B. Synlett, 2002: 1677
[55] Karimi B, Seradj H, Ebrahimian R. Synlett, 2000: 623
[56] Karimi B, Ebrahimian G R, Seradj H. Synth Commun, 2002, 32: 669
[57] Battacharya A K, Mujahid M, Natu A A. Synth Commun, 2008, 38:
128
[58] Xu R, Zhang J, Tian Y, Zhou J. J Iran Chem Soc, 2009, 6: 443
[59] Smith G, Reddy C S. Tetrahedron, 2003, 59: 9571
[60] Ziyaei A, Azizi N, Saidi M R. J Mol Catal A, 2005, 238: 138
[61] Aggarwal K K, Fonquerna S, Vennall G P. Synlett, 1998: 849
[62] Chandra K L, Saravanan P, Singh, V K. Synlett, 2000: 359
[63] Carrigan M D, Eash K J, Oswald M C, Mohan R S. Tetrahedron Lett,
2001, 42: 8133
[64] Karimi B, Maleki J. J Org Chem, 2003, 68: 4951
[65] Ghosh R, Maiti S, Chakraborty A, Halder R. J Mol Catal A, 2004,
215: 49
[66] Joshi M V, Narasimhan C S. J Catal, 1993, 141: 308
[67] Jin T S, Ma Y R, Zhang Z H, Li T S. Synth Commun, 1997, 27: 3379
[68] Heydari M M, Bakhtiari K, Bamoharram F F. Catal Commun, 2006,
7: 499
[69] Romanelli G P, Thomas H J, Barnoetti G T, Autino J C. Tetrahedron
Lett, 2003, 44: 1301
[70] Firouzabadi H, Iranpoor N, Nowrouzi F, Amani K. Tetrahedron
Lett, 2003, 44: 3951
[71] Curini M, Epifano M, Marcotullio M C, Rosati O, Nocchetti M.
Tetrahedron Lett, 2002, 43: 2709
[27] Chakraborti A K, Gulhane R. Synlett, 2004: 627

Farhad SHIRINI et al. / Chinese Journal of Catalysis 34 (2013) 695–703
Graphical Abstract
Chin. J. Catal., 2013, 34: 695–703 doi: 10.1016/S1872‐2067(11)60499‐3
A succinimide‐N‐sulfonic acid catalyst for acetylation reactions in absence of a solvent
Farhad SHIRINI*, Nader Ghaffari KHALIGH
University of Guilan, Iran
O
O
R-XH
R-XAc
CH2Cl2, ClSO3H
+
HCl
NH
N
SO3H
Ac2O, SuSA
X= O, S, N
Solvent free, Ice bath-r.t.
R= Alkyl and Aryl
O
O
Solvent free, r.t.
SuSA
R-CHO
R-CH(OAc)2
Succinimide‐N‐sulfonic acid was prepared by a simple route and shown to be an efficient catalyst for the acetylation of a variety alcohols,
phenols, thiols, amines, and aldehydes with acetic anhydride at room temperature under solvent free conditions.
[72] Aggen D H, Arnold J N, Hayes P D, Smoter N J, Mohan R S.
Tetrahedron, 2004, 60: 3675
A G, Stefanov B B, Liu G, Liashenko A, Piskorz P, Komaromi I,
Gomperts R, Martin R L, Fox D J, Keith T, Al‐Laham M A, Peng C
Y, Nanayakkara A, Gonzalez C, Challacombe M, Gill P M W, Johnson
B, Chen W, Wong M W, Andres J L, Gonzalez C, Head‐Gordon M,
Replogle E S, Pople, J A. Gaussian 98, revision A7, Gaussian, Inc,
Pittsburgh PA, 1998
[73] Frisch M J, Trucks G W, Schlegel H B, Scuseria G E, Robb M A,
Cheeseman J R, Zakrzewski V G, Montgomery Jr, J A, Stratmann R
E, Burant J C, Dapprich S, Millam J M, Daniels A D, Kudin K N,
Strain M C, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R,
Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J,
Petersson G A, Ayala P Y, Cui Q, Morokuma K, Malick D K, Rabuck
A D, Raghavachari K, Foresman J B, Cioslowski J, Ortiz J V, Baboul
[74] Shirini F, Khaligh N G. Phosphorus Sulfur Silicon, 2011, 186: 2156
[75] Shirini F, Khaligh, N G. Monatsh Chem, 2012, 143: 631