N,N,N′,N′-tetrabromobenzene-1,3-disulfonamide and poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide) as efficient catalysts for the methoxymethylation of alcohols under solvent-free conditions

Article abstract of DOI:10.1002/jccs.200800092

Methoxymethylation of a variety of alcohols was performed using formaldehyde dimethyl acetal in the presence of N,N,N′,N′- tetrabromobenzene-1,3-disulfonamide [TBBDA] and poly(N-bromo-N-ethyl-benzene-1, 3-disulfonamide) [PBBS] as catalysts at room tempera

Full text of DOI:10.1002/jccs.200800092

632
Journal of the Chinese Chemical Society, 2008, 55, 632-635
N,N,N¢,N¢-Tetrabromobenzene-1,3-disulfonamide and
Poly(N-bromo-N-ethyl-benzene-1,3-disulfonamide) as Efficient Catalysts
for the Methoxymethylation of Alcohols under Solvent-free Conditions
Ramin Ghorbani-Vaghei,* Mohammad Ali Zolfigol, Mostafa Amiri and Hojat Veisi
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamadan, 65174, Iran
Methoxymethylation of a variety of alcohols was performed using formaldehyde dimethyl acetal in
the presence of N,N,N¢,N¢-tetrabromobenzene-1,3-disulfonamide [TBBDA] and poly(N-bromo-N-ethyl-
benzene-1,3-disulfonamide) [PBBS] as catalysts at room temperature and solvent-free conditions. The
methoxymethyl ethers (MOM-ethers) were obtained with good to excellent yields.
Keywords: Alcohols; Formaldehyde dimethyl acetal; TBBDA; PBBS; Solvent-free conditions.
INTRODUCTION
In view of the tremendous versatility of the hydroxyl
conia,10 expensive graphite,11 FeCl3 dispersed on molecu-
lar sieves,12 pyridyl sulfide,13 Sc(OTf)3 and Bi(OTf)3,14 sil-
ica sulfuric acid,15 and H3PMo12O40.xH2O.16 However, many
of these methods suffer from using expensive reagents, high
temperature, strong protic acid conditions or slow reaction
rates. Consequently, there is a need to develop alternative
reagents for this reaction.
group in organic synthesis, a wide variety of methods have
been developed for the protection of hydroxyl groups.1
Methoxymethylation of alcohols is an important organic
transformation2 that is a frequently used protection method
in multistep synthesis due to its stable to strong basic me-
dia, Grignard reagents, diborane, butyllithium, catalytic
hydrogenation and reduction with hydrides. Formaldehyde
dimethyl acetal (FDMA) is a stable, cheap, and commer-
cially available compound that can be used for the prepara-
tion of methoxymethyl ethers from hydroxyl compounds.
However, the activity of FDMAis poor, so a variety of cata-
lysts have been used for activating this reagent, such as
P2O5,3 p-toulenesulfonic acid,4 Nafion-H,5 TMSI,6 molyb-
denum(VI) acetylacetonate,7 BF3,8 envirocat,9 sulfated zir-
RESULTS AND DISCUSSION
More recently our group has exploited the application
of [TBBDA] and [PBBS]17-25 as mild reagents in organic
synthesis. Prompted by these results, herein we wish to re-
port a simple, mild and efficient method, for the direct meth-
oxymethylation of alcohols with [TBBDA] and [PBBS] as
new catalysts at room temperature and under solvent-free
conditions (Scheme I).
Scheme I
R1
R1
TBBDA or PBBS
OH
OCH2OCH3
R2
FDMA, Solvent-
Free, rt
R2
R1= aryl, alkyl
R2= H, alkyl
Br
Br
Br
Br
N
N
Br
Br
N
N
S
S
S
CH2
S
CH2
)
n
O
O
O
O
O
O
O
O
TBBDA
* Corresponding author. Fax: (+98) 8118272404; E-mail: rgvaghei@yahoo.com
PBBS

Solvent-free Methoxymethylation
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 633
Table 1. Methoxymethylation of alcohols with TBBDA (A) and
PBBS (B) under solvent-free conditions
Table 2. Comparison of reaction time and yield of our reagents
with previously published methods
Entry
1
Substrate
Reagents Time (h) Yielda (%)
Substrate
Conditions
TBBDA
Time (h) Yield (%)
A
B
A
1
1.2
2
1000
95
1.1
2
98
95
OH
OH
OH
OH
OH
PBBSA
Br
Br
Br
65
OH
Sc(OTf)3, CHCl3,
reflux
3
9814
8515
8516
2
3
4
5
B
A
B
A
B
A
B
A
3
1.3
2
60
95
90
98
95
90
95
98
O2N
OH
Silica sulfuric acid,
CH3CN, RT
2.5
3.5
F
1.1
2
OH
H3PMo12O40.xH2O,
Solvent-free, RT
Br
Br
2
OH
Cl
2.4
2
Br
TBBDA
PBBS
2
98
95
OH
OH
OH
Cl
2.2
Cl
6
OH
OH
Cl
B
2.2
90
Cl
Silica sulfuric acid,
CH3CN, RT
0.42
4
7815
A
B
A
B
A
B
A
1.2
1.3
1
1000
90
7
8
9
Cl
Cl
Cl
85
OH
OH
H3PMo12O40.xH2O,
Solvent-free, RT
8616
1.1
1
75
H3CO
Cl
95
TBBDA
4
85
80
1.3
2
90
OH
OH
H3 C
PBBSA
4.2
OH
75
Silica sulfuric acid,
CH3CN, RT
4
6515
10
B
2.2
60
A
B
A
B
A
B
A
B
A
B
A
2
1.45
4
80
75
85
80
80
80
75
60
90
88
-
CH2CH2OH
11
12
13
14
15
verted into the corresponding methoxymethylated products
in good to excellent yields. We found that [TBBDA] and
[PBBS] can be used for the methoxymethylation of primary
and secondary alcohols by formaldehyde dimethyl acetal.
During our investigation, we also found that hindered ter-
tiary alcohols such as 1-adamantanol and 2-methyl-2-pro-
panol were methoxymethylated in refluxing CH3CN with
low yields. The results of the conversion of various alco-
hols are presented in Table 1. Furthermore, our examina-
tion showed that this method is not applicable for protec-
tion of hydroxyl groups in phenol, and the starting material
was recovered.
OH
4.2
3.5
4
OH
4.1
4.5
3
OH
OH
13
2.5
4
OH
16
17
B
A
B
5
8
8
-
-
-
OH
Cl
a All products are known and their spectra as well as physical data
have been reported in the literature.
Since TBBDA and PBBS contain halogen atoms
which are attached to nitrogen atoms, it is very probable
that these reagents release Br+ in situ which can conduct as
an electrophilic species.17-25 Therefore, the mechanism for
the reaction can be suggested as follows (Scheme II). The
advantages of PBBS and TBBDA over reported reagents in
methoxymethylation of 4-bromobenzyl alcohol, 2,4-dichlo-
robenzyl alcohol, and octanol, are shown in Table 2. In con-
clusion, the advantages of our method are mild reaction
Our experiments show that primary and secondary al-
cohols can be smoothly converted into the corresponding
MOM-ethers in excellent yields. Benzylic alcohols bearing
both electron withdrawing groups such as nitro and halo-
gens (Table 1, entries 2-7) and electron releasing groups
such as methoxy and methyl (Table 1, entries 8-9) are con-

634 J. Chin. Chem. Soc., Vol. 55, No. 3, 2008
Ghorbani-Vaghei et al.
Scheme II
3. Fuji, K.; Nakano, S.; Fujita, E. Synthesis 1975, 276-277.
4. Yadrley, J.-P.; Fletcher, H. Synthesis 1976, 244-245.
5. Olah, G.-A.; Husain, A.; Gupta, B.-G. B.; Narang, S.-C. Syn-
thesis 1981, 471-472.
conditions, high yields, short reaction time, solvent-free
conditions, low cost, and uses eco-friendly catalysts.
EXPERIMENTAL
6. Olah, G.-A.; Husain, A.; Narang, S.-C. Synthesis 1983, 896-
897.
General procedure for methoxymethylation of alco-
hols using FDMA with TBBDA and PBBS
To a stirred solution of alcohol (1 mmol), dimethoxy-
methane (10 mmol) was added [TBBDA] (0.15 mmol) or
[PBBS] (0.1 g) and the mixture was stirred at room temper-
ature under solvent-free conditions. The progress of the re-
action was monitored by TLC (4:1 n-hexan/aceton). After
completion of the reaction, H2O (20 mL) was added and the
mixture was extracted with CCl4 (25 mL), and then the or-
ganic layer was dried over anhydrous Na2SO4 (5 g). The re-
agent was removed by simple filtration. Evaporation of the
solvent under reduced pressure gave the pure product (60-
100%).
7. Kantam, M.-L.; Santhi, P.-L. Synlett. 1993, 429-430.
8. Danheiser, R.-L.; Romines, K.-R.; Koyama, H.; Gee, S.-K.;
Johnson, C.-R.; Medich, J.-R. Org. Synth. 1992, 71, 133-
139.
9. Bandgar, B.-P.; Hajare, C.-T.; Wadgaonkar, P.-P. J. Chem.
Res. (S) 1996, 90-91.
10. Jin, T.-S.; Guo, J.-J.; Yin, Y.-H.; Zhang, S.-L.; Li, T.-S. J.
Chem. Res. (S) 2002, 188-189.
11. Jin, T.-S.; Li, T.-S.; Gao, Y.-T. Synth. Commun. 1998, 28,
837.
12. Patney, H.-K. Synlett. 1992, 567-568.
13. Marcune, B.-F.; Karady, S.; Dolling, U.-H.; Novak, T.-J. J.
Org. Chem. 1999, 64, 2446-2449.
14. (a) Karimi, B.; Mamani, L. Tetrahedron Lett. 2003, 44,
6051-6053. (b) Sreedhar, B.; Swapna, V.; Sridhar, C. Catal.
Commun. 2005, 6, 293-296.
ACKNOWLEDGMENTS
We are thankful to Bu-Ali Sina University, Center of
Excellence of Chemical Methods (CEDCM) for financial
support. With best wishes for you and your colleagues R.
Ghorbani-Vaghei.
15. Niknam, K.; Zolfigol, M.-A.; Khorramabadi, A.; Zare, R.;
Shayegh, M. Catal. Commun. 2006, 7, 494-498.
16. Zolfigol, M.-A.; Shiri, M. Mendeleev Commun. 2005, 165-
166.
Received September 11, 2007.
17. Ghorbani-Vaghei, R.; Jalili, H.; Shahbazee, E.; Veisi, H. J.
Chin. Chem. Soc. 2006, 53, 379-382.
REFERENCES
18. Ghorbani-Vaghei, R.; Shahbazee, E. J. Braz. Chem. Soc.
2005, 16, 647-649.
1. Greene, T.-W.; Wuts, P.-G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1991.
19. Zolfigol, M.-A.; Ghorbani-Vaghei, R.; Mallakpour, S.;
Chehardoli, G.; Choghamani, A.-G.; Yazdi, A.-H. Synthesis
2006, 10, 1631-1635.
2. Occupational Safety and Health Administration, U. S. De-
partment of Labour, Federal Register, 1974, 39(20), 3756.

Solvent-free Methoxymethylation
J. Chin. Chem. Soc., Vol. 55, No. 3, 2008 635
20. Azarifar, D.; Ghasemnejad, H.; Ghorbani-Vaghei, R.; Tajbakhsh,
M. Heterocycles 2006, 68, 2343-2347.
Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 1877-
1881.
21. Azarifar, D.; Nadimi, E.; Ghorbani-Vaghei, R.; Maleki, B.
Mendeleev Commun. 2006, 330-331.
24. Ghorbani-Vaghei, R.; Azarifar, D.; Maleki, B. J. Chin.
Chem. Soc. 2004, 51, 1373-1376.
22. Tajbaksh, M.; Khazaei, A.; Shabani-Mahalli, M.; Ghorbani-
Vaghei, R. J. Russian Chem. Org. 2003, 39, 1117-1118.
23. Ghorbani-Vaghei, R.; Azarifar, D.; Khazaei, A.; Maleki, B.
25. Ghorbani-Vaghei, R.; Zolfigol, M.-A.; Moshfeghifar, N.;
Koukabi, N.; Chehardoli, G. J. Chin. Chem. Soc. 2007, 54,
791-794.