Melamine trisulfonic acid (MTSA): A new efficient catalyst for the chemoselective methoxymethylation of alcohols

Article abstract of DOI:10.1080/00397910903026707

Melamine trisulfonic acid, which is easily prepared by the reaction of melamine with neat chlorosulfonic acid, is able to efficiently catalyze the chemoselective methoxymethylation of alcohols with dimethoxymethane (DMM). All reactions were performed unde

Full text of DOI:10.1080/00397910903026707

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Melamine Trisulfonic Acid (MTSA): A New
Efficient Catalyst for the Chemoselective
Methoxymethylation of Alcohols
Farhad Shirini a , Mohammad Ali Zolfigol b & 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
Published online: 22 Feb 2010.
To cite this article: Farhad Shirini , Mohammad Ali Zolfigol & Jalal Albadi (2010) Melamine Trisulfonic
Acid (MTSA): A New Efficient Catalyst for the Chemoselective Methoxymethylation of Alcohols,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:6, 910-914, DOI: 10.1080/00397910903026707
To link to this article: http://dx.doi.org/10.1080/00397910903026707
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Synthetic Communications1, 40: 910–914, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903026707
MELAMINE TRISULFONIC ACID (MTSA): A NEW
EFFICIENT CATALYST FOR THE CHEMOSELECTIVE
METHOXYMETHYLATION OF ALCOHOLS
Farhad Shirini,1 Mohammad Ali Zolfigol,2 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, which is easily prepared by the reaction of melamine with neat
chlorosulfonic acid, is able to efficiently catalyze the chemoselective methoxymethylation of
alcohols with dimethoxymethane (DMM). All reactions were performed under mild and
completely heterogeneous reaction conditions in good to high yields.
Keywords: Alcohols; heterogeneous reaction conditions; melamine; melamine trisulfonic acid; methoxy-
methylation
Between the several methods available for the protection of the alcoholic hydroxyl
groups, methoxymethylation has attracted the attention of many organic chemists.
This considerable attention can be attributed to the stability of the produced
methoxymethyl (MOM) ethers against reagents such as strong bases, butyl lithium,
lithium aluminium hydride, and Grignard reagents as well as easy removal of the
MOM moiety by acid treatment. Generally, the formation of methoxymethyl ethers
is carried out by the alkylation of alcohols with excess amounts of chloromethyl
methyl ether (CME) in alkaline solution.[1] However, the potent carcinogenic proper-
ties of CME limits the use of this method.
Dimethoxymethane (DMM), a cheap and commercially available reagent, is
the other compound that can be used for the methoxymethylation of alcohols.
Handling of this reagent is easy, but its main drawback is its poor methoxymethylat-
ing power. For the activation of DMM, a variety of catalysts, such as expansive
graphite,[2] Sc(OTf)3,[3] phenylsulfonic acid functionalized mesoporous silica,[4]
Bi(OTf)3,[5] silica sulfuric acid,[6] and metal hydrogen sulfates,[7] have been reported.
Although these methods are improvements, most of them suffer from disadvantages
such as harsh reaction conditions, long reaction times, poor yields, poor selectivity,
use of toxic or expensive reagents, and use of large amounts of DMM. Thus, the
search for new reagents and methods is still of practical importance.
Received March 19, 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
910

METHOXYMETHYLATION OF ALCOHOLS
911
Scheme 1. Preparation of MTSA.
Table 1. Methoxymethylation of alcoholsa,b
Entry
Substrate
Product
Time (h)
Yield (%)
1
2
PhCH2OH
PhCH2OMOM
0.58
0.2
92
90
95
92
85
90
92
90
87
90
2-BrC6H4CH2OH
4-ClC6H4CH2OH
4-MeOC6H4CH2OH
4-NO2C6H4CH2OH
PhCH(OH)Me
2-BrC6H4CH2OMOM
4-ClC6H4CH2OMOM
4-MeOC6H4CH2OMOM
4-NO2C6H4CH2OMOM
PhCH(OMOM)Me
3
0.42
0.13
1.5
4
5
6
0.7
0.3
7
PhCH2CH2OH
PhCH2CH2OMOM
8
PhCH2CH2CH2OH
MeCH2CH2CH2OH
MeCH2CH(OH)Me
PhCH2CH2CH2OMOM
MeCH2CH2CH2OMOM
MeCH2CH(OMOM)Me
0.3
0.3
9
10
0.5
11
12
0.7
1
90
80
13
14
15
0.53
1
95
82
Ph3COH
Ph3COMOM
PhOMOM
0.92
1
90
0
16
17
PhOH
PhCH2OH
þ
PhCH2OMOM
þ
100c
þ
0.6
PhOH
PhOMOM
0c
aProducts were characterized by comparison of their physical and spectral data with authentic
samples.[4,11,13,14]
bIsolated yields.
cConversion.

912
F. SHIRINI, M. A. ZOLFIGOL, AND J. ALBADI
Scheme 2. Methoxymethylation of alcohols catalyzed by MTSA.
In recent years, the introduction of new methods and reagents for protection of
alcoholic hydroxyl groups became an important part of our research program.[8–11]
In continuation of these studies, we have found that melamine (I), a cheap and
commercially available reagent, reacts with neat chlorosulfonic acid to give melamine
trisulfonic acid (II) at room temperature. The reaction is easy and clean and needs no
special workup procedure (Scheme 1).
The structure of MTSA assured us that this reagent can act as an efficient
catalyst in reactions that need acidic reagents to speed them up. Our investigations
clarified that this prediction is correct, and the conversion of alcohols to their corre-
sponding MOM ethers is efficiently promoted in the presence of MTSA (Table 1,
Scheme 2). All reactions were performed in CHCl3 at reflux temperature under
completely heterogeneous reaction conditions in good to high yields. Phenols remain
intact under the same reaction conditions (Table 1, entry 16). Therefore, the method
can be useful for the chemoselective methoxymethylation of alcohols in the presence
of phenols (Table 1, entry 17).
The efficiency of the present method is illustrated by the comparison of some of
our results with some of those reported in the literature (Table 2).[3–7]
In conclusion, melamine trisulfonic acid, a newly prepared reagent, is
efficiently able to catalyze the methoxymethylation of alcohols with DMM. Good
yields of the products, short reaction times, heterogeneous nature of the reaction
conditions, use of the relatively small amounts of DMM, ease of preparation,
stability of the reagent, and easy workup procedure are important features of the
reported method.
Table 2. Comparison of some of the results obtained by our method (I) with those reported using
Sc(OTf)3 (II),[3] phenylsulfonic acid functionalized mesoporous silica(III),[4] Bi(OTf)3 (IV),[5] silica sulfuric
acid (V),[6] and Al(HSO4)3 (VI)[7]
Time (h)=yield (%)=DMM–substrate
Entry
Substrate
I
II
III
IV
V
VI
1
2
PhCH2OH
4-NO2C6H4CH2OH
0.58=92=4
—
—
1.5=85=4 5=94=50 6=28.4=5
1=95=8
—
1.5=85=10 1.67=83=30
12.5=80=10 12=75=30
3
4
0.7=90=4 7=80=50
0.92=90=4 7=77=50
—
—
4=85=8 16.5=78=10 17.5=85=30
—
8=70=10
8.5=75=30

METHOXYMETHYLATION OF ALCOHOLS
913
EXPERIMENTAL
General
Chemicals were purchased from Fluka, Merck, and Aldrich chemical compa-
nies. All of the products are known compounds and were characterized by spectral
analyses, comparisons with authentic samples (IR and NMR), and regeneration of
the corresponding alcohols. All yields refer to the isolated products. The purity
determination of the substrate and reaction monitoring were accompanied by gas
chromatography (GC) or thin-layer chromatography (TLC) on silica-gel polygram
SILG=UV 254 plates.
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
solution (i.e., water). Melamine (3.16 g, 25.07 mmol) was added in small portions
over a period of 30 min at room temperature. HCl gas evolved from the reaction
vessel immediately (Scheme 1). After completion of the addition of melamine, the
mixture was shaken for 30 min; meanwhile, the residual HCl was removed by
suction. 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: n ¼ 3133, 2621, 1654, 1509, 1175,
1069 cmꢁ1. 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%.
General Procedure
A mixture of the substrate (1 mmol), DMM (4 mmol, 0.304 g), and MTSA
(0.1 mmol, 0.04 g) in CHCl3(3 mL) was stirred at reflux temperature. The progress
of the reaction was monitored by TLC. After completion of the reaction, the solvent
was evaporated, and Et2O (5 mL) was added. The mixture was filtered, and the solid
residue was washed with Et2O (5 mL). The filtrate was washed with a saturated
solution of NaHCO3 and H2O and dried over MgSO4. Evaporation of the solvent
afforded the requested MOM ether in high purity.
ACKNOWLEDGMENT
We are thankful to the University of Guilan Research Council for the partial
support of this work.
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914
F. SHIRINI, M. A. ZOLFIGOL, AND J. ALBADI
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