4262
S. Paul et al. / Tetrahedron Letters 43 (2002) 4261–4265
Table 1. Mono- and di-acetylation of hydrazine hydrate
according to different supported reagents (power=300 W)
dipolar transition state results under MW irradiation
when compared with its less polar ground state,24 and
the activation energy is consequently reduced.
Reagent
Time (min)
Yield (%)a
In conclusion, we have developed a rapid, safe and
eco-friendly method for N-, O- and S-acetylations using
Ac2O–Py over basic alumina under microwave irradia-
tion. The method is inexpensive and the support can be
reused several times after washing and drying.
AcNHNH2 AcNHNHAc
AcOH/SiO2
0.25
100
0
0
100
80
70
90
60
50
0
12
8
4
8
8
8
2
6
6
1
5
5
AcOH/K-10
AcOH/p-TsOH/SiO2
20
30
10
40
50
100
10
0
General procedure
AcOH/acidic Al2O3
AcOH/TFA/SiO2
AcOH/H2SO4/SiO2
Ac2O/DMSO/SiO2
AcOH/DMSO/SiO2
Ac2O–Py/Basic Al2O3
To a mixture of substrate (2 mmole), acetic anhydride
(4 mmole), pyridine (0.6 mmole), 4 g of basic alumina
were added in a beaker (50 mL). The mixture was
stirred for 30 s until a free flowing powder was
obtained. The reaction mixture (monitored by TLC)
was then irradiated in a microwave oven for an appro-
priate time (Table 2) at 300 W. After cooling down to
room temperature, the product was extracted with
methylene chloride (3×15 mL). The combined organic
extracts were washed with water and dried over sodium
sulfate. The product, obtained after removal of the
solvent under reduced pressure, was crystallized from
an appropriate solvent.
90
0
100
0
0
0
100
0
Ac2O/SiO2
a Yield of isolated products.
The method is environmentally friendly, as acetic acid
(by-product) remains adsorbed over the basic alumina
and there is no evaporation into the atmosphere. The
method can be used for the selective mono- and
diacetylations only by regulating the irradiation time
(entries 19, 20; 28, 29; 30, 31; 38, 39; 41–44).
1
The structures of the products were confirmed by H
NMR, IR and comparison with an authentic sample
prepared by reported methods. H NMR spectra were
recorded using a JNM-PMX 60 NMR spectrometer (60
MHz) and IR spectra by using KBr discs on a Hitachi
270-30 spectrophotometer.
1
In order to operate in an eco-friendly way, we have
carried out the acetylation of aniline under different
conditions. After several experiments testing molar
ratios and amounts of support, we found that for 1
mmole of the reagent, 2 mmoles of Ac2O and 0.6
mmole of pyridine gave optimum results. The amount
of support was also found to be crucial in order to
carry out the reaction in Green Chemistry conditions
and it has been found that for 1 mmole of the reagent,
2 g of the support were required.
The spectral data of entry 2, 33–44
Entry 2. IR cm−1 (KBr): 1707 (COCH3); 1H NMR
(CDCl3): l 2.27 (s, 6H, 2×COCH3). Entry 33. IR cm−1
1
(KBr): 1586 (CꢀN), 1720 (COCH3); H NMR (CDCl3):
Further, the reaction has been carried out at different
power levels ranging from 80 to 800 W for aniline and
2-nitroaniline in order to select the most appropriate
power level (300 W). The results are shown graphically
in Fig. 1.
l 2.24 (s, 3H, COCH3), 7.66–7.80 (m, 6H, Harom). Entry
34. IR cm−1 (KBr): 1576 (CꢀN), 1725 (COCH3); 1H
NMR (CDCl3): l 2.26 (s, 3H, ArCH3), 2.40 (s, 3H,
COCH3), 7.66–7.80 (m, 5H, Harom). Entry 35. IR cm−1
1
(KBr): 1582 (CꢀN), 1720 (COCH3); H NMR (CDCl3):
l 2.26 (s, 3H, COCH3), 4.36 (bs, 1H, NH, exchangeable
with D2O), 7.26–8.1 (m, 5H, Harom). Entry 36. IR cm−1
Finally, the acetylations of 2-, 3- and 4-nitroanilines
were carried out using a thermostated oil-bath under
the same conditions of time and temperature as for
microwave-assisted method (Table 3).
1
(KBr): 1590 (CꢀN), 1722 (COCH3); H NMR (CDCl3):
l 2.26 (s, 3H, COCH3), 4.35 (bs, 1H, N, exchangeable
with D2O), 7.06–8.0 (m, 5H, Harom). Entry 37. IR cm−1
1
(KBr): 1596 (CꢀN), 1730 (COCH3); H NMR (CDCl3):
It has been found that significantly lower yields were
obtained using oil-bath heating rather than the
microwave-assisted method under identical conditions
of reaction and temperature. This observation demon-
strates clearly that the effect of microwave irradiation is
not purely thermal. These specific MW effects might
originate in the rate-determining step of the mechanism
(nucleophilic attack of the amine nitrogen lone pair on
carbonyl moiety) since it leads to a development of
charges in the transition state thus inducing an impor-
tant exaltation in dipole–dipole interactions (Scheme 1).
In this circumstance, an increased stabilization of the
l 2.23 (s, 3H, COCH3), 4.43 (bs, 1H, NH, exchangeable
with D2O), 6.9–7.23 (m, 5H, Harom). Entry 38. IR cm−1
1
(KBr): 1576 (CꢀN), 1725 (COCH3); H NMR (CDCl3):
l 2.33 (s, 3H, COCH3), 7.16–7.96 (m, 5H, Harom). Entry
39. IR cm−1 (KBr): 1586 (CꢀN), 1720 (COCH3); 1H
NMR (CDCl3): l 2.23 (s, 6H, 2×COCH3), 4.20 (bs, 1H,
NH, exchangeable with D2O), 7.26–8.70 (m, 5H,
Harom). Entry 40. IR cm−1 (KBr): 3300, 3460 (NH2),
1720 (COCH3); 1H NMR (CDCl3): l 2.35 (s, 6H,
COCH3), 7.06–7.95 (m, 6H, Harom). Entry 41. IR cm−1
(KBr): 3300, 3460 (NH2), 1700 (COCH3); 1H NMR
(CDCl3): l 2.23 (s, 3H, COCH3), 2.34 (s, 3H, ArCH3),