Microwave assisted amine formylation by a heterogeneous HCO 2H/SiO2 system

Article abstract of DOI:10.1002/jccs.200700067

A simple, fast and efficient procedure has been developed for the synthesis of formamides by treating a silica gel/formic acid mixture with amines under microwave irradiation.

Full text of DOI:10.1002/jccs.200700067

Journal of the Chinese Chemical Society, 2007, 54, 479-481
479
Microwave Assisted Amine Formylation by a Heterogeneous HCO H/SiO2
2
System
Ahmad Khoramabadi-zad,* Hojat Veisi, Safar-Ali Akbari and Azam Shiri
Department of Chemistry, Bu-Ali Sina University, Hamadan 65174, Iran
A simple, fast and efficient procedure has been developed for the synthesis of formamides by treating
a silica gel/formic acid mixture with amines under microwave irradiation.
Keywords: Microwave-assisted reaction; Formylation; Amines; Formic acid; Silica gel.
INTRODUCTION
N-formylation of amines (in both cases, DMSO has been
used as solvent).
Keeping in view our general interest in the develop-
ment of friendlier synthetic procedures, we have succeeded
in rapid, high yield preparation of formamides under mi-
crowave irradiation by the aid of a silica gel/formic acid
heterogeneous system in which the solid silica support may
be recycled after product separation.
4
formic acid, activated formic acid esters, ammonium
,5
6-9
1
formate, and formic acid itself.
0
11,12
HCO2H/SiO2
Lipshutz and cowork-
RR'NCHO
RR'NH
microwave
ers have claimed the use of N-methoxy-N-methylform-
1
amide for the first time as a formylating compound.
3
R =H, alky or aryl; R' = alkyl or aryl
Bagno and coworkers in their paper with 32 references
have focused on preparation and mechanistic investiga-
Therefore, a good range of primary and secondary
amines (aliphatic as well as aromatic) were chosen and sub-
jected to a series of reaction conditions. In this manner, we
succeeded in developing a very convenient and efficient
procedure for the preparation of formamides (Table 1). As
Table 1 shows, the yields are good to excellent (70-99%)
and the reaction times range from 35 to 95 seconds, which
are much lower than those reported in other works (as an
example see ref. 12). It is notable that the reaction times for
entries 6 and 10 of Table 1 are somewhat higher than those
of others, which may be due to their volatility. However,
there is no explanation for entry 5 (reaction time: 90 sec-
onds).
1
4
tions of new formylating agents. Hegedus and coworkers
have prepared dibenzylformamide and diallylformamide
by refluxing a mixture of the corresponding diamine and
1
5
ethyl formate (for 72 h and 22 h respectively).
RESULTS AND DISCUSSION
Disadvantages of most of the above-cited references
are long reaction times and unstable and/or toxic reagents.
On the other hand, the use of solid supported reagents ac-
companying microwave irradiation has become a powerful
synthetic tool for the rapid synthesis of a variety of organic
compounds, because of altering reactivity, simplicity in op-
As mentioned above, mono- and disubstituted form-
amides may be prepared in good to excellent yields and in
very short times. A typical example is the preparation of
1,4-piperazinedicarboxaldehyde from piperazine (entry 4),
which we have prepared in 35 seconds and in 99% yield.
This compound has also been prepared in 1954 by Fujii, K.
1
6-26
eration, mild reaction conditions and improved yields.
In the last reference the authors, after failure in catalytic
transfer hydrogenation, have demonstrated the use of Al
supported HCOOH or their polymer supported formate for
2
O
3
*
Corresponding author. E-mail: khoram@basu.ac.ir

4
80 J. Chin. Chem. Soc., Vol. 54, No. 2, 2007
Khoramabadi-zad et al.
Table 1. Formylation of amines with HCO H/SiO under microwave irradiation
2
2
Product
mp or bp (°C)
Reaction Time
Entry
1
Amine
(sec)
Yield%
96
Found
Reported
NH2
b
40
Mp 59
54-58
NH
c
2
3
4
51
60
35
82
92
99
Mp 70
Mp 50
Mp 128
72
N
H
d
52
e
f
HN
NH
126-127
5
6
H NCH CH NH
2
90
85
85
80
Mp 109-111
Bp 176-177
110-112
2
2
2
c
Et NH
2
176-178
NH
g
7
8
54
45
90
84
Mp 60
62.5-63.5
O
h
Bp 237
236-237
N
H
c
9
72
95
91
70
Bp 222
220-222
196-198
N
H
c
1
0
EtNH2
Bp 202-204
a
Yields refer to the pure isolated products, and the identity of each product was characterized
1
13
by H and C NMR data, which are compatible with the authentic samples.
Bredereck, H.; Gompper, R.; Rempfer, H.; Klemm, K. Chem. Ber. 1959, 92, 329-37.
Olah, G.; Kuhn, I. Chem. Ber. 1956, 89, 2211-12.
b
c
d
e
f
Henbest, H. B.; Thomas, A. J. Chem. Soc. 1967, 3032-39.
Horrom, B. W.; Freifelder, M.; Stone, G. R. J. Am. Chem. Soc. 1955, 77, 753-54.
Runti, C.; Sindellari, L.; Ulian, F. Ann. Chem. 1960, 50, 847-57.
Maglio, M. M. J. Am. Chem. Soc. 1949, 71, 2949-50.
Olah, G. A. J. Org. Chem. 1984, 49, 3856.
g
h
(
temperature: 40-50 °C; time: 30 min.; yield: 77%; bp
1
:
EXPERIMENTAL
Starting materials were obtained from Fluka Com-
1
67-70 °C) and then used in 1956 to formylate thio-
2
7,28
phene.
A recent German patent has also described form-
ylation of several primary and secondary amines, including
2
piperazine, in 62-87%.
pany. Melting points were determined by electrothermal
melting point apparatus (without further correction). IR
and NMR spectra were run using Perkin-Elmer FT-IR and
9
In conclusion, the present microwave assisted form-
ylation by a silica gel/formic acid system under microwave
irradiation provides an efficient, fast, convenient and easy
workup procedure for the synthesis of mono- and disubsti-
tuted formamides. It should be noted that the product yields
for the heterocyclic amines (Table 1, entries 8 and 9) are
Jeol 90 MHz FT NMR spectrometers, respectively. The
1
solvent for all H NMR spectra was CDCl
3
. The source of
microwave radiation was the LG domestic microwave oven
(model MG-583MC).
2
6
much higher than those of Desai and coworkers. In addi-
2 2
Preparation of the HCO H/SiO
tion, the first step of our procedure – irradiation of the
1 mL of formic acid was added to 1 g of silica gel
(mesh 70-230) with stirring for 1 minute at room tempera-
ture.
amine and HCO
2 2
H/SiO mixture – proceeds without the
need of any solvent.

Microwave Assisted Organic Reaction
J. Chin. Chem. Soc., Vol. 54, No. 2, 2007 481
9
. Duczek, W.; Deutsch, J.; Vieth, S.; Niclas, H. J. Synthesis
Preparation of formamides
1
996, 37.
Amine (1 mmol, as liquid or fine powder) and the
above mixture were mixed thoroughly and then subjected
to the 80% power radiation of our domestic microwave
oven for a certain period of time. The progress of each reac-
tion was monitored by TLC using n-hexane/acetone (3:1)
as the solvent. After completion of the reaction the ob-
tained mixture was allowed to cool, eluted with ethanol, fil-
tered and followed either by crystallization or successive
solvent evaporation and vacuum distillation.
1
0. Reddy, P. G.; Kumar, G. D. K.; Baskaran, S. Tetrahedron
Lett. 2000, 41, 9149.
1
1. Treppendhal, S.; Jakobsen, P. Acta Chem. Scand. 1978, Ser
B, B32, 697.
1
1
1
1
1
1
2. Jung, S. H.; Ahn, J. H.; Park, S. K.; Choi, J.-K. Bull. Korean
Chem. Soc. 2002, 23, 149.
3. Lipshutz, B. H.; Pfeiffer, S. S.; Chrisman, W. Tetrahedron
Lett. 1999, 40, 7889.
4. Alessandro, Willi, B. K.; Oliver, S.; Jens, V.; Georg, Z. Eur.
J. Org. Chem. 2001, 2947.
5. Hegedus, L. S.; Borel, C.; Krebs, J.; Satoh, S. J. Am. Chem.
Soc. 1987, 109, 1101.
ACKNOWLEDGMENT
6. Yadav, Y. S.; Reddy, B. V. S.; Venugopal, Ch.; Padmavani, B.
Tetrahedron Lett. 2004, 45, 7507.
7. Paul, S.; Gupta, V.; Gupta, R.; Loupy, A. Tetrahedron Lett.
We are thankful to the Research Council of Bu-Ali
Sina University for partial support of this work.
2
003, 44, 439.
1
1
2
8. Abramovitch, R. A. Org. Prep. Proc. Int. 1991, 23, 685.
9. Caddick, S. Tetrahedron 1995, 51, 10403.
0. Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.;
Jacquault, P.; Mathe, D. Synthesis 1998, 1213.
Received April 27, 2006.
2
2
1. Varma, R. S. Green Chem. 1999, 43.
2. Yadav, J. S.; Reddy, B. V. S. Tetrahedron Lett. 2002, 43,
1
905.
REFERENCES
2
2
3. Yadav, J. S.; Reddy, B. V. S.; Madan, Ch.; Kumar, G. M.
Synlett 2001, 1781.
1
2
. (a) Green, T. W.; Wuts, P. G. M. Protective Groups in Or-
ganic Synthesis; Wiley-Interscience: New York, 1999; Chap-
ter 7. (b) Huffman, C. W. J. Org. Chem. 1958, 23, 727.
. Strazzolini, P.; Giumanini, A. G.; Gauci, S. Tetrahedron
4. Yadav, J. S.; Reddy, B. V. S.; Rasheed, M. A.; Kumar, H. M.
S. Synlett 2000, 487.
25. Yadav, J. S.; Reddy, B. V. S. New J. Chem. 2000, 24, 489.
6. Desai, B.; Danks, T. N.; Wagner, G. Tetrahedron Lett. 2005,
2
1
990, 46, 1081.
4
6, 955.
7. Fujii, K.; Tomino, K.; Watanabe, H. J. Pharm. Soc. Jpn.
954, 74, 1049.
3
4
5
6
7
8
. Blicke, F. F.; Lu, C.-J. J. Am. Chem. Soc. 1952, 74, 3933.
. Waki, J.; Meienhofer, J. J. Org. Chem. 1977, 42, 2019.
. Chen, F. M. F.; Benoiton, N. L. Synthesis 1979, 709.
. Yale, H. L. J. Org. Chem. 1971, 36, 3238.
2
1
2
2
8. Fujii, K.; Yukawa, A. Pharm. Soc. Jpn. 1956, 76, 607.
9. Scherberich, P.; Pfeifer, W. D. Ger. Offen., 2335990, Cl, C
. Kisfaludi, L.; Laszlo, O. Synthesis 1987, 510.
. Neveux, M.; Bruneau, C.; Dixneuf, P. H. J. Chem. Soc.
Perkin Trans. 1 1991, 1197.
0
7c [Chem. Abstr., 1975, 82, P156278a].