Role of water and p-fluorobenzoic acid in mn(ii)t(p-cl)pp catalyzed aerobic oxidation of p-fluorotoluene

Article abstract of DOI:10.14233/ajchem.2013.13016

A solvent-free manganoporphyrin-catalyzed oxidiation of p-fluorotoluene was developed, using oxygen as a clean and cheap oxidant. The parameters that have relationship with conversion were investigated. The conversion of p-fluorotoluene was found to be depend on the stability of catalytic environment. Water and p-fluorobenzoic acid were the final oxidation products of p-fluorotoluene, would inhibit the activity of catalyst. The conversion would be increased from 7.0 to 16.5 %, by the dehydration of acetic anhydride.

Full text of DOI:10.14233/ajchem.2013.13016

Asian Journal of Chemistry; Vol. 25, No. 1 (2013), 313-315
http://dx.doi.org/10.14233/ajchem.2013.13016
Role of Water and p-Fluorobenzoic Acid in Mn(II)T(p-Cl)PP
Catalyzed Aerobic Oxidation of p-Fluorotoluene
*
YONG-QIN FANG , CHUN-XU LV and MING LU
School of Chemical Engineering, Nanjing University of Science and Technology,Nanjing, Jiangsu Province, P.R. China
*Corresponding author: Fax: +86 519 86330198; Tel: +86 519 86330180; E-mail: fyq_cczu@126.com
(Received: 4 November 2011;
Accepted: 23 July 2012)
AJC-11870
A solvent-free manganoporphyrin-catalyzed oxidiation of p-fluorotoluene was developed, using oxygen as a clean and cheap oxidant.
The parameters that have relationship with conversion were investigated. The conversion of p-fluorotoluene was found to be depend on
the stability of catalytic environment. Water and p-fluorobenzoic acid were the final oxidation products of p-fluorotoluene, would inhibit
the activity of catalyst. The conversion would be increased from 7.0 to 16.5 %, by the dehydration of acetic anhydride.
Key Words: p-Fluorotoluene, Manganoporphyrin, Water, p-Fluorobenzoic acid.
provide a better understanding of the catalytic behavier of
metalloporphyrin in oxidation reaction.
INTRODUCTION
The oxidation derivates of p-fluorotoluene play important
roles in the field of medicine manufacture, such as paroxetine,
rosuvastatin, mosapride citrate1-3, etc.
EXPERIMENTAL
Gas chromatography analysis was performed on a Fuli-
9790 chromatograph equipped with a 30 m × 0.25 mm × 0.25 µm
SE54 capillary column and a flame ionization detector. MS spectra
were measured on a Shimadzu GCMSQP2010. p-Fluorotoluene
was distilled and analyzed by GC before use. Mn(II)T(p-Cl)PP
was synthesized and purified according to documented proce-
dures11. Other reagents and solvents were all analytical grade.
25 mL of p-fluorotoluene and a measured amount of
Mn(II)T(p-Cl)PP were charged into a 100 mL autoclave reactor
with nitrogen at 0.85 MPa. The reaction mixture was heated to
180 ºC under magnetic stirring. The oxygen was injected to
replace the nitrogen three times and then charged to 0.85 MPa.
The loss of pressure was recorded every hour and the system
was recharged to 0.85 MPa. After the loss of pressure was less
than 0.01 MPa per hour, the mixture was cooled, neutralized by
1 mol/L NaOH. p-Fluorobenzoic acid was obtained by filtering
the water phase neutralized by 1 mol/L HCl. The organic phase
was identified by GC-MS and quantified by GC using chloro-
benzene as the internal standard. GC analysis was carried out
as follows: nitrogen was used as the carrier gas, at the flow rate
of 30 mL/min; the column temperature was 120 ºC; the injector
temperature was 200 ºC; and the detector temperature was 200 ºC.
Nowadays, these oxidation derivates are synthesized by
the chlorination of p-fluorotoluene followed by hydrolysis in
industry. However, the corrosion of reactors and the serious
environment threat have become the major drawbacks4. During
the past decades, metalloporphyrins have been widely used as
cytochrome P-450 models catalyzing the oxidation of various
substrates in association with a wide variety of oxygen donors
such as iodosylarenes5, sodium periodate6, hydrogen peroxide7,
etc.
However, because of the inertness of saturated hydrocarbon,
few reports are available for the oxidation of toluene using
molecular oxygen as oxidant8-10. Furthermore, the electrophilic
reactivity of high valence metalloporphyrin could be decreased
due to the electron-withdrawing effect of fluorine atom.
Guo and co-workers have demonstrated a solvent-free
biomimetic oxidation system to the aerobic oxidate of toluene,
which used simple metalloporphyrin without any co-reduc-
tants8. However, the application of this method in industry is
hindered due to the low conversion. Although the catalysts
can be recycled by supported metalloporphyrins on different
carriers9,10, the conversion of toluene was limited to 10 %. Thus,
the development of a efficency procedure for such transfor-
mation remains a highly desired goal for organic chemists.
Herein, we report the Mn(II)T(p-Cl)PP-catalyzed biomimetic
oxidation of p-fluorotoluene using oxygen. This work may
RESULTS AND DISCUSSION
The oxidation of p-fluorotoluene by Mn(II)T(p-Cl)PP
is shown in Scheme-I. The main oxidation products were

314 Fang et al.
Asian J. Chem.
p-fluorobenzaldehyde and p-fluorobenzoic acid and only trace
p-fluorobenzyl alcohol could be detected by GC-MS. The
blank experiment confirmed that p-fluorotoluene could not
be oxidized in the absence of Mn(II)T(p-Cl)PP.
is that superfluous catalyst in homogeneous system would
collide with each other and convert to inactive dimer13.
Effect of water on oxidation reaction: It is well known
that the hydroxylation of methyl group in biological systems
via a free radical pathway14. As a free radical inhibitor, water
would quench the reaction. In present case, the oxidation
reaction could not run by adding 3 wt % of water. To further
understand of this phenomenon, we studied the oxidation of
p-fluorotoluene in the presence of acetic anhydride, as shown
in Scheme-II. The main oxidation products were p-fluoro-
benzaldehyde, p-fluorobenzoic acid and p-fluorobenzyl
acetate. The curves of pressure variations are shown in Fig. 1
and the effects of the amount of acetic anhydride on the
conversion of p-fluorotoluene and the product selectivity are
shown in Table-3.
CH2OH
+
CHO
CH3
COOH
Mn(II)T(p-Cl)PP, O2
+
180 ºC, 0 8. 5 MPa
F
F
F
F
trace
Scheme-I: Oxidation of p-fluorotoluene catalyzed by Mn(II)T(p-Cl)PP
Effect of temperature on oxidation reaction: The effects
of reaction temperatures on the conversion of p-fluorotoluene
and the product selectivity are shown in Table-1.
O
CHO
COOH
CH2O C CH3
CH3
TABLE-1
EFFECT OF TEMPERATURE ON OXIDATION REACTION
Mn(II) T(p-Cl)PP, Ac O, O
2
2
+
+
Selectivity (%)
180 ºC, 0.85MPa
Temperature
(oC)
Conversion
(%)
p-Fluorobenzal-
dehyde
-
p-Fluoroben-
zoic acid
-
F
F
F
F
150
160
170
180
190
-
Scheme-II: Oxidation of p-fluorotoluene in the presence of acetic anhydride
catalyzed by Mn(II)T(p-Cl)PP
86.8
54.1
24.2
16.6
13.2
1.7
3.6
7.0
5.3
45.9
75.8
83.4
p-Fluorotoluene, 25 mL; catalyst, 0.8 mg (4.0 × 10-5 mol/L), pressure:
System 1
0.35
0.85 MPa
System 2
0.30
0.25
0.20
0.15
0.10
0.05
0.00
-0.05
As can be seen from Table-1, the reaction could not take
place below 150 ºC and the conversion increased until the
temperature is elevated to180 ºC. Compared with the reported
optimum reaction temperature of toluene in 160 ºC8, the
optimum temperature of p-fluorotoluene is much higher. This
is at least partly due to the electron-withdrawing effect of
fluorine atom. However, because metalloporphyrin is easily
oxidized by oxygen under high temperature9, the improvement
of conversion should be resolved by other pathways.
Effect of the amount of catalyst on oxidation reaction:
The effects of the amount of catalyst on the the conversion of p-
fluorotoluene and the product selectivity are listed in Table -2.
-5
0
5
10
15
20
25
30
35
40
Time (h)
Fig. 1. Curves of pressure variations in different oxidation systems. System
1: p-fluorotoluene, 25 mL; catalyst, 0.8 mg, temperature, 180 ºC;
pressure, 0.85 MPa, System 2: p-fluorotoluene, 25 mL; acetic
anhydride, 4.4 g; catalyst, 0.8 mg; temperature, 180 ºC; pressure,
0.85 MPa
TABLE-2
EFFECT OF THE AMOUNT OF CATALYST ON
OXIDATION REACTION
Selectivity (%)
Catalyst
(mol/L)
Conversion
(%)
p-Fluorobenzal-
dehyde
p-Fluorobenzoic
acid
TABLE-3
EFFECT OF THE AMOUNT OF ACETIC ANHYDRIDE
ON OXIDATION REACTION
1.0 × 10-5
2.0 × 10-5
4.0 × 10-5
6.0 × 10-5
8.0 × 10-5
32.5
30.3
24.2
32.9
36.7
67.5
69.7
75.8
67.1
63.3
1.5
2.8
7.0
6.2
4.5
Selectivity (%)
Acetic
anhydride
(wt %)
Conversion
p-
Fluorobenz- Fluoroben- Fluorobenzyl
p-
p-
(%)
aldehyde
24.2
zoic acid
75.8
acetate
-
p-Fluorotoluene, 25 mL; temperature, 180oC; pressure, 0.85MPa
0
7.0
13.1
16.5
5.4
10
15
20
50
17.8
71.8
10.6
12.8
15.2
16.3
18.3
68.9
The results indicate that the conversion of p-fluorotoluene
increases significantly with the increasment of catalyst loading
from 1.0 × 10-5 to 4.0 × 10-5 mol/L. But the conversion decreases
with the further increasment of catalyst. This phenomenon is
contrary to supported metalloporphyrins12. A probable reason
17.1
67.8
18.0
65.7
3.2
p-Fluorotoluene, 25 mL; catalyst, 0.8 mg, temperature, 180 ºC;
pressure, 0.85 MPa

Vol. 25, No. 1 (2013)
Role of Water and p-Fluorobenzoic Acid in Mn(II)T(p-Cl)PP Catalyzed Aerobic Oxidation 315
The results indicate that p-fluorobenzyl alcohol can be
protected by esterification with acetic anhydride and the
conversion increases significantly with the increase of the
amount of acetic anhydride from 0 to 15 wt %, because of the
dehydration effect of acetic anhydride. However, the conver-
sion decreases with further increase of acetic anhydride.
As can be seen from Fig. 1, in the oxidation system with
acetic anhydride, the rate of oxygen consumption decreases
rapidly in the initial 5 h, which is quite different to another
system. This means that, although the conversion could be
increased by removing water from the reaction system, there
is still some fact inhibit the oxidation reaction. Owning to
strong coordination effect, acetate could be used as an axial
ligand and attached to metalloporphyrin15. However, the
excessive axial ligand would decrease the catalytic activity of
metalloporphyrin16. Hence, it is supposed that p-fluorobenzoic
acid also played the same role as acetate in the oxidation
reaction.
Conclusion
This work studies the application of metalloporphyrin for
the oxidation of p-fluorotoluene without any solvent or
co-reductants. Water and p-fluorobenzoic acid, which are the
final oxidation products of p-fluorotoluene would inhibit the
catalytic activity of metalloporphyrine. Hence, not only the
improvement of the structure of metalloporphyrin but also
stablility of catalytic system should be considered.
ACKNOWLEDGEMENTS
The authors acknowledged the assistance from Nanjing
University of Science and Technology.
REFERENCES
1. W.R. Scott, T.S. Neville, L. Zhao and N. Ran, WO Patent 2009005647
(2009).
2. P. Benkic, D. Bevk, R. Lenarsic, S. Zupancic, A. Vajs and D. Jakse, WO
Patent 2010081861 (2010).
3. M.S. Hashmi, M.K. Madhra and M.I. Inamdar, WO Patent 2011107903
(2011).
Effect of p-fluorobenzoic acid on oxidation reaction:
The effects of the amount of p-fluorobenzoic acid on the
conversion of p-fluorotoluene and the product selectivity are
listed in Table-4.
4. G. Billeb and P. Burg, US Patent 5347054 (1994).
5. T. Nakano, S. Kawabata, T. Sugihara, N. Agatsuma, H. Kakuda and Y.
Mori, Bull. Chem. Soc. Jpn., 76, 2353 (2003).
6. M. Moghadam, S. Tangestaninejad, V. Mirkhani, I. Mohammadpoor-
Baltork, N. Sirjanian and S. Parand, Bioorg. Med. Chem., 17, 3394
(2009).
TABLE-4
EFFECT OF THE AMOUNT OF p-FLUOROBENZOIC
ACID ON OXIDATION REACTION
7. P. Tagliatesta, D. Giovannetti, A. Leoni, M.G.P.M.S. Neves and J.A.S.
Cavaleiro, J. Mol. Catal. A: Chem., 252, 96 (2006).
8. C.C. Guo, Q. Liu, X.T. Wang and H.Y. Hu, Appl. Catal., 282, 55 (2005).
9. G. Huang, F. Xiang, T.M. Li,Y.X. Jiang andY.A. Guo, Catal. Commun.,
12, 886 (2011).
Selectivity (%)
p-
Conversion
(%)
Fluorobenzoic
acid (g)
p-Fluorobenz-
aldehyde
p-Fluoro-
benzoic acid
10. G. Huang, J. Luo, C.C. Cai, Y.A. Guo and G.W. Luo, Catal. Commun.,
9, 1882 (2008).
0.5
1.0
1.5
2.0
2.5
31.7
68.3
67.6
65.9
60.4
58.7
5.7
3.6
1.2
0.7
0.5
32.4
11. A.D. Adler, F.R. Longo, J.D. Finarelli, J. Goldmacher, J. Assour and L.
Korsakoff, J. Org. Chem., 32, 476 (1967).
34.1
39.6
12. H. Kargar, M. Moghadam, V. Mirkhani, I. Mohammadpoor-Baltork,
S. Tangestaninejad and M. Naghipour, Polyhedron, 30, 1463 (2011).
13. J.E. Lyons, P.E. Ellis and H.K. Myers, J. Catal., 155, 59 (1995).
14. B. Meunier, S.P. Visser and S. Shaik, Chem. Rev., 104, 3947 (2004).
15. J. Poltowicz and J. Haber, J. Mol. Catal. A: Chem., 220, 43 (2004).
16. D. Mohajer and L. Sadeghian, J. Mol. Catal. A: Chem., 272, 191 (2007).
41.3
p-Fluorotoluene, 25 mL; catalyst, 0.8 mg, temperature, 180 oC;
pressure, 0.85 MPa
As can be seen from Table-4, the conversion decreases
with increase of the amount of p-fluorobenzoic acid. The
oxidation reaction is nearly terminated when the amount of
p-fluorobenzoic acid is up to 0.08 g/mL. This observation
supported the aforementioned supposition.