Microwave-assisted acetylation of phenols without catalyst under solvent free condition

Article abstract of DOI:10.14233/ajchem.2014.17746

Etherification between phenols with acetic anhydride was tested under different conditions. Phenols were efficiently acylated with acetic anhydride to give phenol acetate derivatives in good high yields without catalyst and solventless conditions under microwave irradiation.

Full text of DOI:10.14233/ajchem.2014.17746

Asian Journal of Chemistry; Vol. 26, No. 22 (2014), 7746-7748
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17746
Microwave-Assisted Acetylation of Phenols without Catalyst Under Solvent Free Condition
1,*
1
1
2
1
1
YU-QUAN ZHANG , YAN-CHUN LI , JI-HUA ZHU , ZHI-FENG LI , GUO-ZHE GUO and DONG-PING CHEN
1College of Chemistry and Chemical Engineering, Longdong University, Lanzhou Road 54 Xifeng, Qingyang 745000, P.R. China
2College of Life Science and Chemistry, Tianshui Normal University, Tianshui 741001, P.R. China
*Corresponding author: E-mail: zhyq118@sohu.com
Received: 2 April 2014;
Accepted: 6 June 2014;
Published online: 6 November 2014;
AJC-16226
Etherification between phenols with acetic anhydride was tested under different conditions. Phenols were efficiently acylated with acetic
anhydride to give phenol acetate derivatives in good high yields without catalyst and solventless conditions under microwave irradiation.
Keywords: Acetylation, Phenols, Microwave irradiation.
procedures. Avoiding organic solvent during the reactions in
INTRODUCTION
organic synthesis leads to a clean, efficient and economical
The acylation of hydroxyl groups is one of the most
technology: safety is largely increased. Working is considerably
frequently used transformations in organic synthesis. Among
simplified, cost is reduced increased amount of reactants,which
can be used34. Microwave irradiation has become increasingly
the various protecting groups used for the hydroxyl function,
acetyl is the most common group in view of its easy introduction,
popular in recent years to improve the yield and shorten reaction
times in a variety of reactions35-37. Reactive and selective some-
being stable to the acidic reaction conditions and also easily
removable by mild alkaline hydrolysis1. Typically, acylation
times are enhanced. Some microwave irradiation assisted
solventless acetylation were describled using catalyses38. Here
of alcohols and phenols is performed under homogeneous
catalysis with acetic acid or acetyl chloride or anhydride, in
we report acetylation of phenols using acetic anhydride as
the presence of a convenient basic catalyst such as triethyl-
acetylating agent without catalyst and solventless conditions
under microwave irradiation, as shown in Scheme-I:
amine or pyridine2. In addition, 4-(dimethylamino)pyridine,
4-pyrrolidinopyridine3. Tetramethylethylenediamine4, tertiary
phosphines5, carbon tetrabromide in ethyl acetate6, p-toluene-
MWI
Ar OOCCH3
3a
(CH3CO)2O
2
+
Ar OH
1
sulfonic acid7, zinc chloride8, iodine9, sulfamic acid10, magnesium
bromide11, cobalt chloride12, tantalum chloride13, La(OPr-i)314,
silica gel-supported sodium hydrogen sulfate15, montmori-
llonite K-10 and KSF16, alumina17, yttria zirconia with acetic
acid18,Ac2O-pyridine/basic alumina under microwave irradia-
tion19, KF-Al2O3 with Ac2O/AcCl20, vanadyl(V) acetate21,
distannoxane22, zeolite HSZ-36023, Pseudo-monas cepacia PS
lipase adsorbed on Celite24, and twisted amides25 have also
been applied for the acetylation of alcohols and phenols.
Another important development has been the introduction of
trifluorme-thanesulfonate derivatives, such as TMSOTf26,
3i
Scheme-I
EXPERIMENTAL
All the reagents employed in the synthesis were of analy-
tical reagent grade. The materials were used as purchased and
used directly without any additional purification. Melting
points were determined on an XT-4 electro thermal micro
melting point apparatus and are uncorrected. Infrared spectra
were measured as KBr discs (or liquid film) using an Alpha
1
Yb-(OTf)327, Cu(OTf)228, Sc(OTf)329, In(OTf)330, Bi(OTf)331
,
centaurispectrometer. H NMR spectra (200 MHz) were
cerium(III)32 and (IV)33 salts as efficient catalysts in acetylation
with acetic acid, or anhydride or acetyl chloride.All these ways
lead to wastes as well as some reactions involving solvents,
often toxic, polluting and longer time.
recorded in CDCl3 using a BRUKER PT 200 spectrometer.
Mass spectra were obtained on a Qp-1000A GC-MS spectro-
meter using the electron impact mode (70 or 20 eV). Microwave
irradiation was carried out with a domestic microwave oven
GlanzWP 750B at 2450 Hz. Sonication was performed in
Shanghai SK-250LH ultrasonic cleaner with the frequency of
There is an increasing interest in the use of environmentally
benign reagents and conditions. Particularly to solvent free

Vol. 26, No. 22 (2014)
Microwave-Assisted Acetylation of Phenols without Catalyst Under Solvent Free Condition 7747
59 kHz. KF/Al2O3 was prepared according to reference20.The
remaining chemicals were obtained from commercial sources.
General procedure: To a mixture of phenols (5 mmol)
and acetic anhydride (6 mmol) were added in a bottle (50 mL)
and irradiated at 675 W for 10 min in microwave oven. After
cooling to room temperature, then reaction mixture was diluted
with water (50 mL) and extracted with ethyl acetate (2 × 50
mL). The organic layer was washed with satd NH4Cl solution
(30 mL) and NaHCO3 solution (25 mL) and brine (40 mL),
respectively. The organic layer dried over MgSO4 and concen-
trated to give the product.
isolation, a large number of ultrasonic reactions40 can be carried
out in higher yield, shorter reaction time or milder conditions,
this prompted us to investigate its use for acetylation purposes.
To demonstrate the catalysis of KF/Al2O3, the reaction
was carried out with high speed stirring, ultrasonic irradiation
and microwave irradiation conditions in the absence of
KF/Al2O3 catalyst, it was concluded that the acetylation of
2-naphthol with acetic anhydrides could not happen with high
speed stirring at 135 °C and under ultrasonic irradiation.
However, it was observed that compound 3h (Table-2 entry 7)
was obtained in 92 % yield in 10 min. When KF/Al2O3 was
used to catalyze the reaction of 2-naphthol with acetic anhy-
drides, the acetylation of 2-naphthol with acetic anhydrides
could not happen at 135 °C with high speed stirring and
ultrasonic irradiation, while in the presence of KF-Al2O3
catalys and microwave, compound 3h was also obtained in
92 % yields in 10 min (Table-2 entry 2,3,4,5,6), these result
revealed that microwave can effectively accelerate the reaction,
KF/Al2O3 was no effective for acetylation of 2-naphthol with
acetic anhydrides.
RESULTS AND DISCUSSION
The results for a variety of esterifcation compounds are
summarized in the Table-1, various types of phenols with elec-
tron donating and withdrawing groups were rapidly acylated
with acetic anhydride and afforded the corresponding phenol
acetate in excellent yields under microwave irradiation without
catalyst and solventless conditions.
The different mole ratios of esterifcation of 2-naphthol
with acetic anhydrides was studied under microwave
irradiation, the results show the best mole ratio is 2-naphthol:
acetic anhydrides = 1:1.2.
We investigated the effects of irradiation power and time
on the reaction. It was found that the highest yield of
compounds is obtained at a power level of 675 W for 10 min
continuous irradiation.
TABLE-1
RESULTS FOR A VARIETY OF ETHERIFICATION
COMPOUNDS WITHOUT CATALYSES AND COLVENTFREE
CONDITIONS UNDER MICROWAVE IRRADIATIONa
Productb
Phenols
Phenol
4-Methyl phenol
3-Nitro phenol
1,2-Catechol
1,4-Quinol
1,3,5-Triphenol
1-Naphthol
2-Naphthol
Yields (%)c
m.p. oC/Lit
Oil41
96
95
90
94
94
88
90
92
93
3a
Oil42
3b
52-53(53-5441)
62-63°C (62-63 °C43)
121-122(120-12143)
101-103(102-10343)
45-46(44-4541)
68-69(67-6941)
77-79(77-7841)
3c
3d
3e
Conclusion
3f
3g
In summary, a simple, safe and eco-efficient method for
acetylation of phenols has been developed. The method has
advantages in terms of yields, short reaction times, ease of
operation and compatibility with other protecting groups. We
believe that the present methodology could be an important
addition to the existing methodologies.
3h
4-Nitro phenol
3i
aConditions: Aryl phenols (5 mmol), acetic anhydride (6 mmol), 675
W for 10 min. bAll products gave satisfactory 1H NMR, Mass spectra
and IR. cYield of isolated product
To expore the scope and versatily of this method, different
reaction conditions were investigated. Highlighted in
Table-2 for 2-naphthol acetate (3h), for example, is the influ-
enece of catalysts, reaction time, mole ratios, ultrasound wave
and microwave on the reaction yield.
ACKNOWLEDGEMENTS
The authors thank Scientific and Research Projects of
Department of Education of Gansu Province for 2012 and the
Longdong University Science Technology Development
Foundation (XYZK0504) for financial support.
Since KF/Al2O339 is a new kind of highly active catalytic
catalysts that can catalyze many reactions under mild condi-
tions, to give high yields, the high efficacy and ease of product
TABLE-2
OPTIMIZATION OF THE REACTION CONDITION
Entry
Catalyst (mmol %) KF/Al2O3
Method
MWI
MWI
MWI
MWI
MWI
MWI
MWI
Ultrasound
Ultrasound
Time (min)
bYields (%)
60a
1
2
3
4
5
6
7
8
9
0.3
0.3
0.3
0.3
0.5
0.7
0
6
8
78a
10
12
10
10
10
40
40
92a (0c)
89a
92a
92a
92a (0c)
(0d)
0.3
0
(0d)
Conditions: 2-naphthol (5 mmol), acetic anhydride (6 mmol). aMicrowave irradiation at 675 W. bYield of isolated product. cReaction temperature
135 °C, high speed stirring reaction time 5 h, without microwave irradiation. dReaction temperature 20-25 °C, ultrasound irradiation at 59 kHz

7748 Zhang et al.
Asian J. Chem.
24. P.Allevi, P. Ciuffreda,A. Longo and M. Anastasia, Tetrahedron Asymm.,
9, 2915 (1998).
REFERENCES
25. S.Yamada, T. Sugaki and K. Matsuzaki, J. Org. Chem., 61, 5932 (1996).
26. P.A. Procopiou, S.P.D. Baugh, S.S. Flack and G.G.A. Inglis, Chem.
Commun., 2625 (1996).
1. A.L. Pearson and W.J. Roush, Handbook of Reagents for Organic Syn-
thesis: Activating Agents and Protecting Groups; John Wiley & Sons:
UK, pp. 9-16 (1999).
27. A.G.M. Barrett and D. Christopher Braddock, Chem. Commun., 351
(1997).
28. K.L. Chandra, P. Saravanan, R.K. Singh and V.K. Singh, Tetrahedron,
58, 1369 (2002).
29. K. Ishihara, M. Kubota, H. Kurihara and H. Yamamoto, J. Am. Chem.
Soc., 117, 4413 (1995).
30. K.K. Chauhan, C.G. Frost, I. Love and D. Waite, Synlett, 1743 (1999).
31. G. Bartoli, M. Bosco, E. Marcantoni, L. Sambri and E. Torregiani,
Synlett, 209 (1998).
2. R.I. Zhdanov and S.M. Zhenodarova, Synthesis, 222 (1975).
3. W. Steglich and G. Hofle, Angew. Chem. Int. Ed. Engl., 8, 981 (1969).
4. T. Sano, K. Ohaschi and T. Oriyama, Synthesis, 1141 (1999).
5. E. Vedejs, N.S. Bennett, L.M. Conn, S.T. Diver, M. Gingras, S. Lin,
P.A. Oliver and M.J. Peterson, J. Org. Chem., 58, 7286 (1993).
6. H. Hagiwara, K. Morohashi, H. Sakai, T. Suzuki and M. Ando, Tetra-
hedron, 54, 5845 (1998).
7. A.C. Cope and E.C. Herrick, Org. Synth., 4, 304 (1963).
8. R.H. Baker and F.G. Bordwell, Org. Synth., 3, 141 (1955).
9. R. Borah, N. Deka and J.C. Sarma, J. Chem. Res. Synop., 110 (1997).
10. T.S. Jin, J.R. Ma, Z.H. Zhang and T.S. Li, Synth. Commun., 28, 3173
(1998).
32. G. Bartoli, G. Cupone, R. Dalpozzo, A. De Nino, L. Maiuolo, A.
Procopio, L. Sambri and A. Tagarelli, Tetrahedron Lett., 43, 5945
(2002).
33. K. Tanaka and F. Toda, Chem. Rev., 100, 1025 (2000).
34. P. Lidström, J. Tierney, B. Wathey and J. Westman, Tetrahedron, 57,
9225 (2001).
35. J. Hamelin, J.-P. Bazureau, F. Texier-Boullet in ed.: A. Loupy, Microwaves
in Organic Synthesis, Wiley-VCH, Weinheim, pp. 253-294 (2002).
36. (a) Y.-Q. Zhang, J. Chem. Res., 365 (2013); (b) L. Bai, J.-X. Wang and
Y.M. Zhang, Green Chem., 5, 615 (2003).
11. E. Vedejs and O. Daugulis, J. Org. Chem., 61, 5702 (1996).
12. J. Iqbal and R.R. Srivastava, J. Org. Chem., 57, 2001 (1992).
13. S. Chandrasekhar, T. Ramachander and M. Takhi, Tetrahedron Lett.,
39, 3263 (1998).
14. T. Okano, K. Miyamoto and K. Kiji, Chem. Lett., 24, 246 (1995).
15. G.W. Breton, J. Org. Chem., 62, 8952 (1997).
16. A.X. Li, T.S. Li and T.H. Ding, Chem. Commun., 1389 (1997).
17. S.S. Rana, J.J. Barlow and K.L. Matta, Tetrahedron Lett., 22, 5007
(1981).
37. N. Deka, A.-M. Mariotte and A.Ã. Boumendjel, Green Chem., 3, 263
(2001).
38. T.Ando, J.Yamawaki, T. Kawate, S. Sumi and T. Hanafusa, Bull. Chem.
Soc. Jpn., 55, 2504 (1982).
18. P. Kumar, R.K. Pandey, M.S. Bodas and S.P. Dagade, J. Mol. Catal.
Chem., 181, 207 (2002).
39. T.J. Mason and D. Peters, Practical Sonochemistry, Ellis-Horwood,
London (2002).
19. P. Paul, P. Nanda, R. Gupta and A. Loupy, Tetrahedron Lett., 43, 4261
(2002).
40. M. Aloe, Rend. Accad. Sci. Napoli, 27, 75 (1921).
41. F.D. Chattaway, J. Chem. Soc., 2495 (1931).
42. J. Buckingham and S.M. Donghy, Dictionary of Organic Compounds,
Chapman and Hall, New York, edn. 5 (1982).
20. V.K. Yadav, K.G. Babu and M. Mittal, Tetrahedron, 57, 7047 (2001).
21. B.M. Choudary, M.L. Kantam and V. Neeraja, J. Mol. Catal. Chem.,
140, 25 (1999).
22. A. Orita, K. Sakamoto, Y. Hamada, A. Mitsutome and J. Otera, Tetra-
hedron, 55, 2899 (1999).
23. R. Ballini, G. Bosica, S. Carloni, L. Ciaralli, R. Maggi and G. Sartori,
Tetrahedron Lett., 39, 6049 (1998).