Microwave assisted direct ortho-acylation of phenol and naphthol derivatives by BF3·(C2H5)2O

Article abstract of DOI:10.1246/bcsj.78.284

The solventless acylation of phenol and naphthol derivatives with various organic acids and BF₃·(C₂H₅) ₂O, under microwave conditions, was studied. High yields of the o-acylated products were achieved in a very short time.

Full text of DOI:10.1246/bcsj.78.284

2
84 Bull. Chem. Soc. Jpn., 78, 284–287 (2005)
Ó 2005 The Chemical Society of Japan
Microwave Assisted Direct Ortho-Acylation of Phenol
and Naphthol Derivatives by BF Á(C H ) O
3
2
5 2
ꢀ
Hossein Naeimi and Leila Moradi
Chemistry Department, Faculty of Sciences, Kashan University, Kashan, 87317, I. R. Iran
Received May 31, 2004; E-mail: naeimi@kashanu.ac.ir
The solventless acylation of phenol and naphthol derivatives with various organic acids and BF3 (C2H5)2O, under
ꢁ
microwave conditions, was studied. High yields of the o-acylated products were achieved in a very short time.
Friedel–Crafts acylations are very important reactions
carried out industrially. Intermediates for pharmaceutical,
perfumes, flavors, fragrances, dyes, plastics, antioxidants,
Results and Discussion
For the first time, we attempted to carry out acylation reac-
tions of phenol and naphthol derivatives with acetic acid in the
1
stabilizers, fungicides, etc., are prepared using these reactions.
This type reaction employs acid chloride or anhydride in the
presence of catalysts, like aluminum chloride or tin(IV) chlo-
ride. Acylation can also be achieved by treating the free acid
with a variety of condensing agents. These include liquid hy-
presence of BF3 (C2H5)2O under a solvent-free condition and
ꢁ
microwave irradiation (Scheme 1). The results are indicated in
Table 1. As shown in this Table, using of BF3 gave regioselec-
tively ortho acylated products in very high yields, and within
short reaction times.
The yields of the reaction products can be compared with
the yields of acylated phenol or naphthol derivatives in previ-
ously reported acylation methods in which a Lewis acid is
employed as a catalyst.
In this reaction, acylation occurred as highly regioselective
toward ortho hydroxy alkyl aryl ketones. By using of 2,6-di-
methylphenol as a substrate in the reaction, no product was ob-
tained, and the unreacted starting materials were completely
recovered (entry 13).
In these reactions, the reaction rates were increased with the
presence of an electron-donating substituent, and decreased
with the existence of an electron-withdrowing substituent on
phenolic compounds (entries 10, 12, and 14 compared with
the other entries).
2
3
drogen fluoride, concentrated sulfuric acid, phosphorus pent-
4
5
6
oxide, polyphosphoric acid, fluorosulfonic acid, and alumina
in methane-sulfonic acid.7
Aromatic acylation with carboxylic acids instead of acid
anhydrides and acyl chlorides has attracted interest, because
it is an environmentally benign reaction, resulting in the
formation of a Lewis acid–water complex as the only a by-
8
product. The direct acylation of phenol derivatives, using
AlCl3 or TiCl4 as a promoter, also provides useful synthetic
method for the preparation of o-hydroxyaryl ketone deriva-
9
–12
tives.
Recently, while exploring the scope and utility13 of the sol-
id-phase conditions in organic synthesis, it was observed that
the no solvent conditions are also effective for the synthesis
of alkyl and acylarenes.
A solvent-free or solid-state reaction may be carried out us-
ing the reactants alone, or by incorporating them in clays, zeo-
lites, silica, alumina, or matrices. A thermal process or irradi-
ation with UV, microwave or ultrasound can be employed to
bring about the reaction. Solvent-free reactions obviously re-
duce the pollution, and decrease the handling costs due to sim-
plification of the experimental procedure, work-up technique
and saving in labor. These would be especially important dur-
ing industrial production.14
The presence of –OH stretching broad bonds in the 3100–
ꢂ1
3500 cm region and C=O stretching strong bonds in the
ꢂ1
1620–1670 cm IR region, and the existence of a broad sin-
R1
R1
R2
CH3CO2H
R2
BF3
MW
+
R =OH R2=H
1
R =OH R =COCH3
1
2
R2=OH R1=H
R2=OH R1=COCH
3
Microwave-assisted solvent-free synthesis15 in organic reac-
tions has been of growing interest as an efficient, economic,
and clean procedure.16
OH
OH
O
R1
R2
R1
R2
CH3
BF3
MW
+
CH3CO2H
Boron triflouride (BF3) is an inorganic fluorinated gas; it is
highly toxic, colorless, nonflammable, and used as a catalyst in
R3
R3
17–19
many chemical reactions, including polymerization,
2
alkyl-
1
2
3
1
2
3
R =OH R =R =H
R =CH3 R =R =H
0,21
22
2
1
3
2
1
3
ation,
and acylation.
R =OH R =R =H
R =CH3 R =R =H
3
1
2
3
1
2
R =OH R =R =H
R =CH3 R =R =H
3
1
2
1
3
2
In this research, we examined the acylation of phenol and
naphthol derivatives with aliphatic acids and BF3 (C2H5)2O
under microwave conditions to enhance the reaction rate.
R =NO2 R =R =H
R =R =CH3 R =H
2
1
3
1
2
3
R =NO2 R =R =H
R =R =R =H
ꢁ
Scheme 1.
Published on the web February 11, 2005; DOI 10.1246/bcsj.78.284

H. Naeimi et al.
Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
285
aÞ
Table 1. Acetylation of 1 mmol Phenol and Naphthol Derivatives with 1.2 mmol HOAc under BF3 (C2H5)2O
in MW Conditions
ꢁ
Entry
1
Substrate
mmol of BF3
Power/W
600
Time/min
2
Product
Yield/%
95
OH
OH
O
CH3
0.41
OH
COCH3
OH
2
3
4
5
0.41
0.83
0.83
0.41
300
400
300
200
1.7
3
40
90
85
98
OH
OH
OH
O
CH3
O
OH
OH
OH
OH
H3C
H3C
1.3
2
OH
OH
O
O
OH
OH
OH
H3C
6
0.83
300
2
98
OH
OH
OH
OH
O
O
CH3
CH3
H3C
H3C
7
8
0.83
0.41
600
600
2
3
50
98
OH
OH
CH3
CH3
OH
O
OH
H3C
9
0.21
0.83
0.83
800
700
700
1.7
2
98
10
98
CH3
OH
CH3
O
OH
H3C
1
1
0
1
NO2
OH
NO2
OH
O
CH3
CH3
H3C
2
CH3
OH
CH3
1
2
3
0.83
0.83
900
900
2
2
—
0
0
NO2
CH3
OH
H3C
1
—
—
O
OH
1
4
0.83
900
2
0
O
OH
a) mmols of naphthols are 0.70.

2
86 Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
Direct Ortho-Acylation of Phenols
Table 2. Acylation of 1 mmol of p-Cresol with Organic Acids by 0.83 mmol of BF3
bÞ
Entry
aÞ
Acid
mmol of acid
Time/min
Power/W
Yield /%
1
CH3CO2H
C2H5CO2H
C3H7CO2H
C4H9CO2H
PhCO2H
1.2
1.3
1.08
0.95
1.6
1.83
2.5
2
2
2
800
600
700
600
600
98
98
95
98
95
2
3
4
5
a) By 0.21 mmol of BF3. b) Isolated yields.
ꢃ 18 ꢃ
2
-Acetyl-1-naphthol: mp 98–100 C (lit. mp 98 C); IR
ꢂ1
OH
OH
O
1
(
2.6 (s, 3H), 7.5–8.3 (m, 6H), 13.8 (s, 1H).
KBr) ꢁ (cm ): 3300–3600, 1625, 1570; H NMR (CDCl3) ꢀ
BF
3
.(C
2
H
5
)
2
O
R
+
2
RCO H
MW
ꢂ1
1
-Acetyl-2-naphthol: IR (neat) ꢁ (cm ): 3200–3500, 1725,
1
1
1
675; H NMR (CDCl3) ꢀ 2.6 (s, 3H), 7.5–8.0 (m, 6H), 13.8 (s,
H).
CH
3
CH
3
R=CH3,
C
2
H
5
, C
3
H
7
, C
4
H
9
, ph
21
1
-(2-Hydroxy-3-methylphenyl)-1-ethanone:
ꢂ1
oil, (lit. bp
1
ꢃ
8
(
2–84 C) IR (KBr) ꢁ (cm ): 3200–3500, 1650, 1600; H NMR
Scheme 2.
CDCl3) ꢀ 2.2 (s, 3H), 2.6 (s, 3H), 7.5–7.8 (m, 3H), 12.1 (s, 1H).
1
26
glet peak with ꢀ 11.8–13.8 ppm in the H NMR data from all
of the products, is completely consistent with the ortho-acylat-
ed phenols and naphthols.
1-(2-Hydroxy-4-methylphenyl)-1-ethanone:
ꢂ1
oil, (lit. bp
1
ꢃ
82–84 C) IR (KBr) ꢁ (cm ): 3200–3500, 1600, 1670; H NMR
(CDCl3) ꢀ 1.8 (s, 3H), 2.0 (s, 3H), 6.2–7.0 (m, 3H), 11.8 (s, 1H).
ꢃ
In order to develop the use of BF3 in the acylation reaction,
we used various organic acids in the acylation reaction of p-
cresol in the presence of BF3 (C2H5)2O under microwave irra-
1-(2-Hydroxy-5-methylphenyl)-1-ethanone: mp 42–44
C
ꢃ
ꢂ1
(
1
3
lit.17 mp 43–44 C) IR (KBr) ꢁ (cm ): 3300–3500, 1650,
1
775; H NMR (CDCl3) ꢀ 2.2 (s, 3H), 2.4 (s, 3H), 6.8–7.4 (m,
H), 11.8 (s, 1H).
ꢁ
diation and solvent-free conditions (Scheme 2).
1
-(2-Hydroxy-3,5-dimethylphenyl)-1-ethanone:
ꢂ1
oil, IR
The results are given in Table 2. It was considered that the
yields of the reaction products were excellent for acylation re-
actions with all of the various organic acids.
In conclusion, this new method for the acylation of phenol
and naphthol derivatives has some advantages, such as: sim-
plicity of the reaction, very high yields of the products, a short
reaction time, and simplicity of the work-up. In these reac-
tions, ortho aryl alkyl ketones were regioselectively yielded
as the products under efficient, mild, and solvent-free
conditions.
1
(
2
KBr) ꢁ (cm ): 2900–3450, 1770–1650; H NMR (CDCl3) ꢀ
.4 (s, 3H), 2.5 (s, 3H), 2.8 (s, 2H), 7.5 (d, 2H), 12.6 (s, 1H).
ꢃ
17
1
-(2,4-Dihydroxyphenyl)-1-ethanone: mp 143–145 C (lit.
ꢃ
ꢂ1
mp 144–146 C) IR (KBr) ꢁ (cm ): 3000–3500, 1620, 1570;
1
H NMR (CDCl3) ꢀ 2.7 (s, 3H), 6.4 (s, 1H), 7.3–7.7 (m, 3H),
1
2.8 (s, 1H).
1
ꢂ1
-(2,3-Dihydroxyphenyl)-1-ethanone:
oil, IR (KBr) ꢁ
cm ): 3100–3600, 1620, 1490; H NMR (CDCl3) ꢀ 2.8 (s,
H), 6.0 (s, 1H), 6.8–7.6 (m, 3H), 12.4 (s, 1H).
-(2,5-Dihydroxyphenyl)-1-ethanone: mp 197–199 C (lit.
1
(
3
ꢃ
17
1
ꢃ
ꢂ1
mp 198–200 C) IR (KBr) ꢁ (cm ): 3100–3250, 1620, 1500–
Experimental
1
1
(
580; H NMR (DMSO-d6) ꢀ 2.4 (s, 3H), 6.8–7.3 (m, 3H), 8.7
s, 1H), 11.4 (s, 1H).
1-(2-Hydroxyphenyl)-1-ethanone: oil, (lit. bp 213 C) IR
Chemicals were purchased from the Merck Chemical Company
in high purity. BF3 was used in the reactions as BF3 (C2H5)2O,
boron trifluoride etherate (50%). IR spectra were recorded from
a KBr pellet on a Perkin-Elmer 781 spectrophotometer and an
23
ꢃ
ꢁ
ꢂ1
1
(
ꢀ
KBr) ꢁ (cm ): 2600–3300, 1650, 1490; H NMR (DMSO-d6)
2.5 (s, 3H), 6.7 (s, 1H), 6.8–7.6 (m, 4H).
1
1
Impact 400 Nickolet FT IR Spectrophotometer. H NMR were
-(2-Hydroxy-5-methylphenyl)-1-propanone: oil, IR (KBr)
ꢂ1
recorded in CDCl3 with (60 MHz) spectrometer using of TMS
as an internal reference. Melting points were obtained with a
Yanagimoto micro melting-point apparatus, and are uncorrected.
Purity determinations of the substrates and reaction monitoring
were accomplished by TLC on silica-gel polygram SILG/UV
54 plates.
General Procedure for the Acylation Reaction. In the gen-
eral procedure, a mixture of 1 mmol of phenolic or 0.7 mmol of
naphtholic compound, BF3 (C2H5)2O, and 1.2 mmol acetic acid,
1
ꢁ
(
(cm ): 3200, 1720, 1620; H NMR (CDCl3) ꢀ 1.0 (t, 3H), 2.0
s, 3H), 2.6 (q, 2H), 6.5–7.2 (m, 3H), 11.9 (s, 1H).
1
ꢂ1
-(2-Hydroxy-5-methylphenyl)-1-butanone: oil, IR (KBr) ꢁ
cm ): 3300, 1730, 1620; H NMR (CDCl3) ꢀ 1.2 (t, 3H), 1.7 (q,
1
(
2
H), 2.3 (s, 3H), 6.7–7.0 (m, 3H), 7.2 (s, 1H), 11.9 (s, 1H).
1
2
-(2-Hydroxy-5-methylphenyl)-1-pentanone: oil, IR (KBr)
ꢂ1
1
ꢁ
1
(cm ): 3250, 1730, 1630; H NMR (CDCl3) ꢀ 0.7 (t, 3H).
.4 (m, 4H), 2.0 (s, 3H), 2.6 (t, 2H), 6.4–7.0 (m, 3H), 7.2 (s, 1H).
ꢁ
reacted together under microwave irradiation, without any solvent
for a short time. After cooling to room temperature, the reaction
mixture was dissolved in dichloromethane (10 mL) and H2O
We are grateful to the University of Kashan Research Coun-
cil for the partial support of this work.
(
about 20 mL). After extraction of the organic phase, it was wash-
References
ed with aqueous NaHCO3 (20 mL), dried with CaCl2, filtered and
evaporated to give a crude product. The crude products were then
purified by chromatography on silica gel using petroleum ether as
the eluent. The products were confirmed by spectroscopic data and
physical methods by being consistent with the reported data.7
ˇ
1
E. Veverkov a´ , M. Meciarov a´ , B. Gotov, and S. Toma,
Green Chem., 4, 361 (2002).
2 L. F. Fieser and E. B. Hershberg, J. Am. Chem. Soc., 62, 49
(1940).
,23–28

H. Naeimi et al.
Bull. Chem. Soc. Jpn., 78, No. 2 (2005)
287
3
4
5
6
R. D. Haword, J. Chem. Soc., 1932, 1125.
J. W. Cook, J. Chem. Soc., 1932, 1472.
J. Koo, J. Org. Chem., 28, 1134 (1963).
W. Baker, G. E. Coates, and F. Glockling, J. Chem. Soc.,
(1986). b) R. J. Giguere, R. J. Bray, S. M. Duncan, and G.
Majetich, Tetrahedron Lett., 27, 4945 (1986).
17 T. Noto, V. Babushok, D. R. Burgess, A. Iiamins, W.
Isang, and A. Miziolek, ‘‘International Twenty-sixth Symposium
on Combustion/the Combustion in Situe,’’ (1996), p. 1337.
18 G. T. Linteris and L. Truett, Combust. Flame, 105, 15
(1996).
19 V. Babushok, T. Noto, D. R. F. Burgess, A. Hamins, and
W. Tsang, Combust. Flame, 107, 351 (1996).
20 S. C. Potter, D. J. Tildesley, A. N. Burgess, and S. C.
Rogers, Mol. Phys., 92, 825 (1977).
1
951, 1376.
7
28.
8
9
1985).
H. Sharghi and B. Kaboudin, J. Chem. Res., Synop., 1998,
6
I. V. Kozehevinco, Appl. Catal. A, 2003, in press.
B. M. Trost and M. G. Saulnier, Tetrahedron Lett., 26, 123
(
1
0
L. Crombie, R. C. F. Jones, and C. J. Palmer, Tetrahedron
Lett., 29, 2933 (1985).
G. N. Dorofeenko and V. V. Tkachenko, Khim. Geter.
Soedin., 7, 1703 (1971); Chem. Abstr., 76, 153503k (1972).
21 A. J. Mclaughlin, J. R. Bonar, M. G. Jubber, D. V. S.
Marques, S. E. Hicks, and C. D. W. Wilkinson, J. Vac. Sci. Tech-
nol. B, 16, 1860 (1998).
1
1
1
1990).
2
G. Satory, G. Casnati, and F. Bigi, J. Org. Chem., 55, 4371
22 B. K. Smith, J. J. Sniegowski, G. Lavigne, and C. Brown,
Sens. Actuators A, 70, 1590 (1998).
(
1
3
a) F. Toda, K. Tanaka, and K. Hamai, J. Chem. Soc., Per-
23 S. Paul, P. Nanda, R. Gupta, and A. Loupy, Synthesis,
2003, 42485.
24 R. W. Stoughton, J. Am. Chem. Soc., 57, 202 (1935).
25 D. J. Crouse, L. S. Hurlbut, and D. M. S. Wheeler, J. Org.
Chem., 46, 374 (1981).
kin Trans. 1, 1990, 3207. b) F. Toda and H. Akai, J. Org. Chem.,
5, 3446 (1990). c) F. Toda, K. Tanaka, and S. Iwata, J. Org.
Chem., 54, 3007 (1989). d) K. Tanaka, O. Kakinoki, and F. Toda,
J. Chem. Soc., Chem. Commun., 1992, 1053.
5
1
1
4
5
G. Nagendrappa, Resonance, 2002, 59.
a) A. Loupy, J. Petit, and F. Hameline, Synthesis, 1998,
26 A. Bensary and N. T. Zavery, Synthesis, 2003, 267.
27 M. Julia and F. Chastrette, Bull. Chem. Soc. Fr., 1962,
2255.
28 S. Kobayashi, M. Moriwaki, and I. Hachiya, Synlett, 1995,
1153.
1
213. b) R. S. Varma, Green Chem., 1, 43 (1999).
a) R. Gedye, F. Smith, K. C. Westaway, H. Ali, L.
Baldisera, L. Labergl, and J. Rousell, Tetrahedron Lett., 27, 279
1
6