Tribromo melamine as novel and versatile catalyst for the formylation and acetylation of alcohols

Article abstract of DOI:10.1016/S1872-2067(12)60748-7

Tribromo melamine has been found to be an efficient and green organocatalyst for the acetylation and formylation reactions of alcohols with acetic anhydride and ethyl formate at room temperature and under mild reaction conditions.

Full text of DOI:10.1016/S1872-2067(12)60748-7

Chinese Journal of Catalysis 35 (2014) 260–263
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
Tribromo melamine as novel and versatile catalyst for the
formylation and acetylation of alcohols
Maryam Hajjami*, Arash Ghorbani‐Choghamarani, Zahra Karamshahi, Masoomeh Norouzi
Department of Chemistry, Faculty of Science, Ilam University, P.O. Box 69315516, Ilam, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Tribromo melamine has been found to be an efficient and green organocatalyst for the acetylation
and formylation reactions of alcohols with acetic anhydride and ethyl formate at room temperature
and under mild reaction conditions.
Received 23 September 2013
Accepted 13 November 2013
Published 20 February 2014
© 2014, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Tribromo melamine
Acetylation
Formylation
Alcohol
Ethyl formate
Acetic anhydride
1. Introduction
acetate or other ester protecting groups [6–8].
Several acetylation and formylation procedures for alcohols
During the multistep synthesis of natural products, the effi‐
ciency of the synthetic protocol employed often depends large‐
ly on protection and deprotection of the functional groups. To
this end, protecting groups have played a crucial role in the
synthesis of complex natural products [1]. Acetylation and
formylation of hydroxy groups are the most widely used trans‐
formations in organic synthesis [2–4].
Amongst protecting groups for alcohols, esters are the most
important with acetate being the simplest and easiest to use.
Acetylation is usually performed with reagents such as acetic
anhydride or acetyl chloride in the presence of variety of acidic
or basic catalysts [5].
have been reported over the years [9–14], but these methods
suffer from some disadvantages, such as heavy metal contami‐
nation, high temperature, formation of undesirable or toxic
byproducts, expensive reagents, or long reaction times [15–18].
These issues stimulated us to research a simple, efficient, and
safe catalyst for the acetylation and formylation of alcohols. In
this regard, a group of compounds entitled N‐halo reagents is
widely used in fine organic synthesis [19].
2. Experimental
Chemicals were purchased from Fluka, Merck, and Aldrich.
The formylated and acetylated products were characterized by
comparison of their spectral (IR, H NMR, and 13C NMR) and
Formylation is also a very important process in organic
chemistry. O‐Formylation is the method of choice for protecting
an alcoholic group in a complex synthetic sequence because
deformylation can be affected selectively in the presence of
1
physical data with those of authentic samples.
* Corresponding author. Tel/Fax: +98‐8412227022; E‐mail: mhajjami@yahoo.com;m.hajjami@ilam.ac.ir
DOI: 10.1016/S1872‐2067(12)60748‐7 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 35, No. 2, February 2014

Maryam Hajjami et al. / Chinese Journal of Catalysis 35 (2014) 260–263
2.1. Formylation of 4‐tert‐butylbenzyl alcohol
Table 1
Optimization of the amount of tribromo melamine in the reaction of
4‐bromobenzyl alcohol with ethyl formate or acetic anhydride.
To the stirred mixture of 4‐tert‐butyl benzyl alcohol (1
mmol, 0.164 g) and ethyl formate (2 mL), tribromo melamine
(0.1 mmol) was added without additional solvents. The result‐
ing mixture was stirred at room temperature for 30 min. The
reaction was monitored by TLC. On completion of reaction, the
product was extracted with CH2Cl2 (5 mL × 4). The organic
layer was separated, dried over anhydrous Na2SO4 (1.5 g), and
concentrated under reduced pressure. Finally, the organic sol‐
vents were evaporated, and 4‐tert‐butylbenzyl formate was
obtained in 92% yield. The identity of the product was con‐
firmed by comparing the physical and spectral data with those
of the known compound.
Entry
1
2
Catalyst amount (mmol)
Yield a (%)
13
0.01
0.02
40
3
0.03
41
4
0.04
56
5
0.05
99
6
7
No catalyst
0.01
Trace
22
8
0.02
28
9
0.03
30
10
11
12
0.04
57
0.05
No catalyst
95
Trace
2.2. Acetylation of 3‐fluorobenzyl alcohol
Reaction conditions: 4‐bromobenzyl alcohol 1 mmol, ethyl formate 2
mL or acetic anhydride 2 mmol, room temperature.
a Yields refer to isolated pure products.
Tribromo melamine (0.1 mmol) was added to a solution of
3‐fluorobenzyl alcohol (0.126 g, 1 mmol) and acetic anhydride
(0.204 g, 2 mmol) in dichloromethane (5 mL), and the reaction
mixture was stirred at room temperature for 1 h (the progress
of the reaction was monitored by TLC). On completion of the
reaction, water (5 mL) and then 5% NaHCO3 (5 mL) was added
to the mixture with stirring, and the product was extracted
with CH2Cl2 (5 mL × 4). The organic layer was dried over anhy‐
drous Na2SO4 (1.5 g). Finally, the organic solvents were evapo‐
rated, and 3‐fluorobenzyl acetate was obtained in 86% yield.
mation, whereas, in its absence, the reaction fails to initiate
even after 24 h (Table 1, entry 6). Additionally, 4‐bromobenzyl
alcohol was used as a model substrate for acetylation (Table 1,
entries 7–12). The reaction was monitored with different
amounts of catalyst. Increasing the loading of tribromo mela‐
mine from 0.01 mmol to 0.05 mmol resulted in a considerable
improvement of the yield from 22% to 95% (Table 1, entries 7
and 11). The acetylation reaction was also carried out in the
absence of catalyst. Again, the reaction had not initiated after
24 h (Table 1, entry 12).
3. Results and discussion
To find the best solvent for the formylation, the model reac‐
tion was performed in a number of solvents, and moderate to
poor yields of the corresponding alkyl formates were obtained
(Table 2, entry 2–6). A far higher yield was obtained under
solvent‐free conditions (Table 2, entry 1).
Following our previous work in developing new methods
for the protection of the hydroxy group [20–23], an effective
procedure for the acetylation and formylation of alcohols with
acetic anhydride and ethyl formate in the presence of catalytic
amounts of tribromo melamine at room temperature (Scheme
1) has been developed.
The acetylation reaction was also investigated in various
solvents; the model reaction consisted of
1 mmol of
To find the optimal conditions for the formylation of alco‐
hols by this method, we selected 4‐bromobenzyl alcohol as a
model substrate and treated it with ethyl formate in the pres‐
ence of different amounts of tribromo melamine at room tem‐
perature. We found that 0.05 equivalents of tribromo melamine
gave the highest yield of the respective alkyl formate after 60
min at room temperature (Table 1, entry 5). The results clearly
show that the tribromo melamine is effective for this transfor‐
4‐bromobenzyl alcohol with acetic anhydride (2 mmol) using
0.05 mmol of tribromo melamine as the catalyst (Table 2, entry
Table 2
Effect of solvent on the conversion of 4‐bromobenzyl alcohol to the
corresponding formate or acetate.
Entry
1
2
Solvent
Solvent‐free
Acetone
Dichloromethane
Acetonitrile
Ethyl acetate
Chloroform
Solvent‐free
Acetone
Dichloromethane
Acetonitrile
Ethyl acetate
Chloroform
Time (min)
1 h
Yield a (%)
99
40
54
9
58
23
96
95
95
83
99
97
24 h
24 h
24 h
24 h
24 h
240
3
EtOOCH, TBM
4
5
6
7
8
9
ROCOH + EtOH
solvent-free, rt
ROH
Ac O, TBM
2
180
20
ROCOCH + CH COOH
3
3
CH Cl , rt
2
2
10
11
12
165
202
106
BrHN
N
NHBr
TBM = Tribromo melamine
N
N
Reaction conditions: substrate:ethyl formate/acetic anhydride = 1
mmol/2 mmol, catalyst 0.05 mmol, solvent 5 mL.
a Yields refer to isolated pure products.
NHBr
Scheme 1. Formylation and acetylation of alcohols.

Maryam Hajjami et al. / Chinese Journal of Catalysis 35 (2014) 260–263
Table 3
Formylation of alcohols.
Entry
Substrate
Catalyst amount (mmol)
Time (min)
Yield a (%)
1
2
3
4
5
6
7
8
9
4‐Chlorobenzyl alcohol
Benzyl alcohol
0.05
0.05
0.20
0.20
0.15
0.20
0.15
0.10
0.05
0.05
80
30
44
48
70
120
55
30
60
180
97
99
98
96
99
50
93
92
99
23
4‐Fluorobenzyl alcohol
3‐Fluorobenzyl alcohol
2,4‐Dichlorobenzyl alcohol
4‐Nitrobenzyl alcohol
Benzhydrol
4‐t‐Butylbenzyl alcohol
4‐Bromobenzyl alcohol
3‐Pyridinmethanol
10
Reaction conditions: alcohol 1 mmol, ethyl formate 2 mmol.
a Yields refer to isolated pure products.
Table 4
Acetylation of alcohols.
Entry
Substrate
Catalyst amount (mmol)
Time (min)
Yield a (%)
1
2
3
4
5
6
7
8
9
2‐Chlorobenzyl alcohol
Benzyl alcohol
0.05
0.05
0.10
0.10
0.15
0.20
0.10
0.10
0.05
0.10
45
15
50
60
12
95
60
40
20
80
99
99
99
86
84
97
93
98
95
86
4‐Fluorobenzyl alcohol
3‐Fluorobenzyl alcohol
2,4‐Dichlorobenzyl alcohol
4‐Nitrobenzyl alcohol
Benzhydrol
4‐tert‐Butylbenzyl alcohol
4‐Bromobenzyl alcohol
3‐Pyridinmethanol
10
Reaction conditions: alcohol 1 mmol, acetic anhydride 2 mmol.
a Yields refer to isolated pure products.
7–12). Dichloromethane was found to be most effective solvent
giving high yield with comparatively low reaction time (Table
2, entry 9).
were subjected to the formylation reaction to investigate the
chemoselectivity of the proposed system. The formylation of
phenols and non‐benzyl alcohols did not occur under our con‐
ditions, and phenols or non‐benzyl hydroxyl groups remained
unaffected during the reaction (Scheme 2).
As can be seen in Table 4, both electron‐withdrawing and
electron‐donating substituents on the alcohols could be em‐
ployed in the synthesis of acetates.
Our experiments also indicated that non‐benzyl alcohols
were not acetylated under these conditions. This catalytic acet‐
ylating system is also chemoselective so that the acetylation of
benzyl alcohols was selective in the presence of phenols
(Scheme 3). A possible mechanism of these reaction systems is
shown in Scheme 4.
Therefore, we employed these optimized conditions for the
formylation (0.05 mmol tribromo melamine, solvent‐free) and
acetylation (0.05 mmol tribromo melamine in dichloromethane
as the solvent) of various alcohols into the corresponding for‐
mates (Table 3) and acetates (Table 4), respectively.
Different types of alcohols, having both electron withdraw‐
ing and donating groups, were formylated with ethyl formate in
the presence of a catalytic amount of tribromo melamine under
solvent‐free conditions in good to high yields (Table 3, entries
1–9).
Benzyl alcohols, phenols, and non‐benzyl alcohols groups
O
O
OH
OCCH
3
OCH
OH
O
O
O
TBM
rt, CH Cl
2
TBM
rt, solvent-free
Ac O
OH +
+
+
OCCH
2
+
+
+
3
OH
OCH
Et
H
2
Br
Br
Br
Br
100%
O
0%
100%
O
0%
O
O
OH
OCCH
OH
OCH
OCH
OH
Br
3
OCCH
OH
Br
3
O
TBM
rt, solvent-free
TBM
+
+
+
+
Et
H
Ac O
+
2
+
rt, CH Cl
2
2
Br
Br
Br
100%
Br
Br
Br
0%
100%
0%
Scheme 2. Chemoselectivity of formylation.
Scheme 3. Chemoselectivity of the acetylation.

Maryam Hajjami et al. / Chinese Journal of Catalysis 35 (2014) 260–263
Graphical Abstract
Chin. J. Catal., 2014, 35: 260–263 doi: 10.1016/S1872‐2067(12)60748‐7
Tribromo melamine as novel and versatile catalyst for the formylation and acetylation of alcohols
Maryam Hajjami*, Arash Ghorbani‐Choghamarani, Zahra Karamshahi, Masoomeh Norouzi
Ilam University, Iran
EtOOCH, tribromo melamine
ROCOH + EtOH
BrHN
N
NHBr
Solvent-free, rt
ROH
Tribromo melamine =
N
N
Ac2O, tribromo melamine
ROCOCH3 + CH3COOH
CH2Cl2, rt
NHBr
The acetylation and formylation of alcohols with acetic anhydride and ethyl formate in the presence of catalytic amounts of tribromo
melamine at room temperature are described.
O
[2] Shirini F, Zolfigol M A, Mallakpour S. Russ J Org Chem, 2005, 41:
R = C H , CH CO
C
1
2
5
3
625
R1O
R2
R = CH , H
2
3
[3] Shirini F, Zolfigol M A, Abedini M, Salehi P. Bull Korean Chem Soc,
2003, 24: 1683
[4] Lee C W, Hwang H Y, Jeong H M, Yoon U C, Chi K W. Synth Met,
2009, 159: 1820
[5] Niknam K, Saberi D. Tetrahedron Lett, 2009, 50: 5210
[6] Ram R N, Meher K N. Tetrahedron, 2002, 58: 2997
[7] Zolfigol M A, Chehardoli G, Dehghanian M, Niknam K, Shirini F,
Khoramabadi‐Zad A. J Chin Chem Soc, 2008, 55: 885
[8] Niknam K, Saberi D. Appl Catal A, 2009, 366: 220
[9] Ghorbani‐Choghamarani A, Akbaripanah Z. Chin Chem Lett, 2012,
23: 450
BrHN
N
NHBr
Br HN
R2
N
NHBr
O
C
N
N
N
N
R1O
NHBr
NHBr
[10] Singh A S, Bhanage B M, Nagarkar J M. Green Chem Lett Rev, 2012,
5: 27
OH
R
[11] Zareyee D, Alizadeh P, Ghandali M S, Khalilzadeh M A. Chem Pap,
2013, 67: 713
+
R OCOR2 R1OH
Scheme 4. Proposed mechanism for the acetylation and formylation.
[12] Iranpoor N, Firouzabadi H, Davan E E. Tetrahedron Lett, 2013, 54:
1813
[13] Rahmatpour A. C R Chim, 2012, 15: 1048
[14] Li G L, Zhao G. Synth Commun, 2013, 43: 34
[15] Habibi M H, Tangestaninejad S, Mirkhani V, Yadollahi B. Tetrahe‐
dron, 2001, 57: 8333
[16] Niknam K, Zolfigol M A, Saberi D, Khonbazi M. Chin J Chem, 2009,
27: 1548
[17] Mirkhani V, Tangestaninejad S, Moghadam M, Yadollahi B,
Alipanah L. Monatsh Chem, 2004, 135: 1257
[18] Iranpoor N, Firouzabadi H, Jamalian A. Tetrahedron Lett, 2005, 46:
7963
4. Conclusions
We have developed a new strategy for the acetylation and
formylation of alcohols with acetic anhydride and ethyl formate
in the presence of catalytic amounts of tribromo melamine at
room temperature. Our method involves mild reaction condi‐
tions, using very simple and accessible starting materials and
solvents, as well as an inexpensive and non‐toxic catalyst.
[19] Kolvari E, Ghorbani‐Choghamarani A, Salehi P, Shirini F, Zolfigol M
A. J Iran Chem Soc, 2007, 4: 126
Acknowledgements
[20] Hajjami M, Ghorbani‐Choghamarani A, Norouzi M. Chin J Catal,
2012, 33: 1661
[21] Ghorbani‐Choghamarani A, Norouzi M. Bull Korean Chem Soc,
2011, 32: 1399
Financial support from the Ilam University, Ilam, Iran is
gratefully acknowledged.
References
[22] Ghorbani‐Choghamarani A, Norouzi M. Chin J Catal, 2011, 32:
595
[23] Ghorbani‐Choghamarani A, Goudarziafshar H, Zamani P. Chin
Chem Lett, 2011, 22: 1207
[1] Hagiwara H, Morohashi K, Sakai H, Suzuki T, Ando M. Tetrahedron,
1998, 54: 5845