Efficient acetylation of alcohols, phenols, and amines catalyzed by melamine trisulfonic acid (MTSA)

Article abstract of DOI:10.1080/00397910903029941

Melamine trisulfonic acid (MTSA) was easily prepared by the reaction of melamine with neat chlorosulfonic acid at room temperature. This reagent can be used as an efficient catalyst for the acetylation of alcohols, phenols, and amines with Ac₂O under mild and completely heterogeneous reaction conditions.

Full text of DOI:10.1080/00397910903029941

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Efficient Acetylation of Alcohols,
Phenols, and Amines Catalyzed by
Melamine Trisulfonic Acid (MTSA)
Farhad Shirini a , Mohammad Ali Zolfigol b , Ali-Reza Aliakbar a
Jalal Albadi a
&
a Department of Chemistry, College of Science, University of Guilan,
Rasht, Iran
b College of Chemistry, Bu-Ali Sina University, Hamadan, Iran
Version of record first published: 04 Mar 2010
To cite this article: Farhad Shirini, Mohammad Ali Zolfigol, Ali-Reza Aliakbar & Jalal Albadi (2010):
Efficient Acetylation of Alcohols, Phenols, and Amines Catalyzed by Melamine Trisulfonic Acid (MTSA),
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:7, 1022-1028
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Synthetic Communications1, 40: 1022–1028, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903029941
EFFICIENT ACETYLATION OF ALCOHOLS, PHENOLS,
AND AMINES CATALYZED BY MELAMINE
TRISULFONIC ACID (MTSA)
Farhad Shirini,1 Mohammad Ali Zolfigol,2 Ali-Reza Aliakbar,1
and Jalal Albadi1
1Department of Chemistry, College of Science, University of Guilan,
Rasht, Iran
2College of Chemistry, Bu-Ali Sina University, Hamadan, Iran
Melamine trisulfonic acid (MTSA) was easily prepared by the reaction of melamine with
neat chlorosulfonic acid at room temperature. This reagent can be used as an efficient
catalyst for the acetylation of alcohols, phenols, and amines with Ac2O under mild and
completely heterogeneous reaction conditions.
Keywords: Acetylation; alcohols; amines; melamine; melamine trisulfonic acid
Acetic anhydride is one of the most important reagents widely used for the
protection of the alcoholic hydroxyl groups during multistep synthesis. A number
of reagents have been reported for the promotion of the acetylation of alcohols
with Ac2O, including p-toluenesulfonic acid,[1] fluorous distannoxane,[2] heteropo-
lyoxometallates,[3] bismuth(III) salts,[4] NaHSO4 ꢀ SiO2,[5] alumina-supported
MoO3,[6]12-tungstophosphoric acid,[7] manganese(III) bis(2-hydroxyanil)acetylace-
tonato complex,[8] gadolinium triflate,[9] bis (cyclopentadienyl) zirconium dichlor-
ide,[10] 3-nitrobenzeneboronic acid,[11] polymer-supported gadolinium triflate,[12]
niobium(V) chloride,[13] cerium(III) triflate,[14] H14[NaP5W30O110],[15] Al(OTf)3,[16]
N,N-dibromo-4-methylbenzenesulphonimide,[17] TiCl3(OTf),[18] silica sulfuric
acid,[19] Al(HSO4)3,[20] and Zr(HSO4)4.[21] However, some of the reported methods
suffer from one or more of the following disadvantages: high temperature, formation
of undesirable or toxic by-products, tedious workup procedure, long reaction times,
poor yields of the products, thermal instability of the reagents, and use of hazardous,
highly flammable, or expensive reagents. Thus, the search for new reagents and
methods is still of practical importance.
During the course of our studies on the development of new methods for
the functional group transformations,[19–24] we found that melamine (I) reacts with
neat chlorosulfonic acid to give melamine trisulfonic acid (MTSA) (II) at room
Received March 26, 2009.
Address correspondence to Farhad Shirini, Department of Chemistry, College of Science,
University of Guilan, Rasht, 41335-1914, Iran. E-mail: shirini@guilan.ac.ir; fshirini@yahoo.com
1022

ACETYLATION OF ALCOHOLS, PHENOLS, AND AMINES
1023
Scheme 1. Preparation of MTSA.
temperature (Scheme 1). The reaction is easy and, because of the fast evolution of
HCl gas from the reaction vessel, needs no special workup procedure.
On the basis of the structure of MTSA, we anticipated that this reagent could
act as an efficient catalyst in reactions that need the use of acidic reagents to
speed them up. Therefore, we were interested in using MTSA for the promotion
of acetylation of alcohols with Ac2O (Scheme 2, Table 1).
As shown in Table 1, different types of alcohols, including benzylic, primary,
secondary, and tertiary alcohols, are converted to their corresponding acetates when
efficiently catalyzed in the presence of MTSA (Table 1, entries 1–30). All reactions
were performed under mild and completely heterogeneous reaction conditions
with excellent yields. Our investigation clarified that phenols and amines are also
converted to their acetylated forms under the same reaction conditions in good to
high yields (Scheme 3, Table 1, entries 31–47).
It is very important to note that by using this method, by-products resulting
from the dimerization of diarylcarbinols, dehydration of tertiary alcohols, change
in the configuration of optically active alcohols, and Firese rearrangement of phenols
were not observed.
Investigation in the reusability of the catalyst showed that MTSA is reusable
two times (Table 1, entries 2 and 4).
Although the actual role of MTSA is not clear, the mechanism shown in
Scheme 4 is the most probable one.
To illustrate the efficiency of the proposed method, Table 2 compares some of
the results with some of those reported in the literature.[4,8,10–12]
In conclusion, the acetylation of alcohols, phenols, and amines with Ac2O is
efficiently catalyzed in the presence of MTSA, as a newly prepared melamine-based
reagent. Good yields of the products, relatively short reaction times, ease of the prep-
aration, stability of the reagent, heterogeneous nature of the reaction conditions, and
easy workup are among the other advantages of this new method that make this
procedure a useful and attractive addition to the available methods. We are
exploring further applications of MTSA for the other types of functional group
transformations in our laboratory.
Scheme 2. Acetylation of alcohols catalyzed by MTSA.

1024
F. SHIRINI ET AL.
Table 1. Acetylation of alcohols, phenols, and amines catalyzed by MTSAa
Entry
Substrate
Product
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
9
C6H5CH2OH
C6H5CH2OAc
14
8 (10c)
95
90 (90c)
92
90 (87c)
90
94
4-CIC6H4CH2OH
2-CIC6H4CH2OH
2-BrC6H4CH2OH
3-NO2C6H4CH2OH
4-NO2C6H4CH2OH
2-MeOC6H4CH2OH
3-MeOC6H4CH2OH
4-MeOC6H4CH2OH
4-CIC6H4CH2OAc
2-CIC6H4CH2OAc
2-BrC6H4CH2OAc
3-NO2C6H4CH2OAc
4-NO2C6H4CH2OAc
2-MeOC6H4CH2OAc
3-MeOC6H4CH2OAc
4-MeOC6H4CH2OAc
9
11 (12c)
17
12
4
89
85
10
3
90
10
6
92
11
12
13
2-MeC6H4CH2OH
4-Me3CC6H4CH2OH
C6H5CH(OH)Me
2-MeC6H4CH2OAc
4-Me3CC6H4CH2OAc
C6H5CH(OAc)Me
15
12
12
90
87
90
14
15
6
85
85
10
16
17
18
19
20
Ph2CHOH
Ph2CH(OAc)
C6H5CH(OAc)CH2(OAc)
C6H5CH2CH2OAc
9
45
20
22
16
90
90d
92
C6H5CH(OH)CH2OH
C6H5CH2CH2OH
C6H5CH2CH2CH2OH
C6H5CH(Me)CH2OH
C6H5CH2CH2CH2OAc
C6H5CH(Me)CH2OAc
95
90
21
9
90
22
23
24
MeCH2CH2CH2OH
MeCH(Me)CH2CH2OH
C6H5CH2CH(OH)Me
MeCH2CH2CH2OAc
MeCH(Me)CH2CH2OAc
C6H5CH2CH(OAc)Me
22
34
20
85
90
85
25
35
92
26
60
82
27
28
29
70
95
90
90
85
100
30
31
Ph3COH
4-ClC6H4OH
Ph3COAc
4-ClC6H4OAc
100
52
80
90
(Continued )

ACETYLATION OF ALCOHOLS, PHENOLS, AND AMINES
1025
Table 1. Continued
Entry
Substrate
2,4-Cl2C6H3OH
2-PhC6H4OH
Product
2,4-Cl2C6H3OAc
2-PhC6H4OAc
Time (min)
Yield (%)b
32
33
34
95
30
92
90
87
2,4-(NO2)2C6H3OH
2,4-(NO2)2C6H3OAc
145
35
14
85
36
19
90
37
38
4-MeOC6H4OH
4-(PhCH2)C6H4OH
4-MeOC6H4OAc
4-(PhCH2)C6H4OAc
6
8
92
85
39
20
90d
40
41
16
15
95d
85d
42
43
44
45
C6H5NH2
C6H5NHAc
5
3
92
92
90
95
4-MeC6H4NH2
2-MeC6H4NH2
3-CF3C6H4NH2
4-MeC6CH4NHAc
2-MeC6CH4NHAc
3-CF3C6H4NHAc
3
19
46
47
25
13
92
90
PhNHCH3
PhN(Ac)CH3
aProducts were identified spectroscopically.
bIsolated yields.
cResults obtained using recycled catalyst.
dGC yields.
EXPERIMENTAL
Preparation of MTSA
A 250-mL suction flask charged with chlorosulfonic acid (5 mL, 75.2 mmol)
was equipped with a gas inlet tube for conducting HCl gas over an adsorbing sol-
ution (i.e., water). Melamine (3.16 g, 25.07 mmol) was added in small portions over
Scheme 3. Acetylation of phenols and amines catalyzed by MTSA.

1026
F. SHIRINI ET AL.
Scheme 4. Mechanism of the acetylation of alcohols, phenols, and amines.
a period of 30 min at room temperature. HCl gas evolved from reaction vessel
immediately (Scheme 1). After completion of the addition of melamine, the mixture
was shaken for 30 min; meanwhile, the residual HCl was exhausted by suction. The
mixture was triturated with n-hexane (10 mL) and then filtered. The solid residue was
washed with n-hexane (10 mL) and dried under vacuum. Melamine trisulfonic acid
(7.9 g, 87%) was obtained as a white solid, which was stored in a capped bottle.
Mp: 142–144 ꢁC; IR: V ¼ 3133, 2621, 1654, 1509, 1175, 1069 cmꢂ1. Anal. calcd.
for C3H6N6O9S3 (366.3): C, 9.83%; N, 22.95%; H, 1.64%. Found: C, 9.81%; N,
22.95%; H, 1.64%. The presence of three atoms of sulfur per each molecule of MTSA
is confirmed by the titration of MTSA in acetonitrile environment with 1.0 M
Bu4NOH (MeOH), according to the previously reported method.[25]
Table 2. Comparison of some of the results obtained by acetylation of alcohols and phenols in the
presence of MTSA (1), with some of those reported by BiCl3 (2),[4] manganese(III) bis(2-hydroxyanil)
acetylacetonato complex (3),[8] bis(cyclopentadienyl)zirconium dichloride (4),[10] 3-nitrobenzeneboronic
acid (5),[11] and polymer-supported gadolinium triflate (6)[12]
Time (h)=yield (%)
Entry
Substrate
1
2
3
4
5
6
1
2
3
C6H5CH2OH
4-NO2C6H4CH2OH
C6H5CH2CH2OH
0.23=95
0.2=94
0.3=92
0.58=98
0.5=95
1=98
5=97
8=86
5=95
10=93
—
14=90
10=90
12=94
—
1.5=99
1=97
5=96
4
1.1=90
0.3=94
—
15=86
14=97
24=18
5
6
b-Naphthol
Ph3COH
0.32=90
1.7=80
1.5=95
2=0
—
—
10=89
—
—
—
—
—

ACETYLATION OF ALCOHOLS, PHENOLS, AND AMINES
1027
General Procedure
A mixture of the substrate (1 mmol), acetic anhydride (1 mmol), and MTSA
(0.3 mmol, 0.11 g) in CH2Cl2 (3 mL) was stirred at room temperature. After
completion of the reaction (monitored by thin-layer chromatography, TLC), the
mixture was filtered. The filtrate was washed with CH2Cl2 (5 mL). The organic layer
was washed with 5% solution of NaHCO3, then with water, and dried over MgSO4.
Evaporation of the solvent followed by column chromatography on silica gel
afforded the pure acetate.
ACKNOWLEDGMENT
We are thankful to the University of Guilan Research Council for the partial
support of this work.
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