Electrophilic aromatic nitration using perfluorinated rare earth metal salts in fluorous phase

Article abstract of DOI:10.1039/b202308n

In this paper, we describe a practical, useful electrophilic aromatic nitration process in fluorous phase by using perfluorodecalin (C₁₀F₁₈, cis- and trans-mixture) as a fluorous solvent and perfluorinated rare earth metal salt [Yb(OSO₂C₈F₁₇)₃] as a catalyst for the electrophilic aromatic nitration.

Full text of DOI:10.1039/b202308n

Electrophilic aromatic nitration using perfluorinated rare earth metal
salts in fluorous phase
Min Shi* and Shi-Cong Cui
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China. E-mail: mshi@pub.sioc.ac.cn;
Fax: 86-21-64166128
Received (in Cambridge, UK) 5th March 2002, Accepted 13th March 2002
First published as an Advance Article on the web 8th April 2002
In this paper, we describe a practical, useful electrophilic
aromatic nitration process in fluorous phase by using
perfluorodecalin (C10F18, cis- and trans-mixture) as a
fluorous solvent and perfluorinated rare earth metal salt
[Yb(OSO2C8F17)3] as a catalyst for the electrophilic aro-
matic nitration.
were obtained based on the nitric acid. Results are summarized
in Table 1. Sc(OSO2C8F17)3 is the most active catalyst in this
reaction. The fluorous solvents perfluorohexane (C6F14) and
perfluorotoluene (C7F8) are in fact miscible with aromatic
substrate such as toluene. Thus, it is impossible to separate the
fluorous layer containing catalyst from the reaction mixture.
Using perfluoro(methylcyclohexane) (C7F14) or perfluorodeca-
lin (C10F18, cis- and trans-mixture) as the fluorous solvent, the
fluorous phase is not miscible with aromatic substrates and
dissolves only the Ln(OSO2C8F17)3 catalysts. The fluorous
layer can be easily isolated from the reaction mixture and reused
for the next nitration. Ln(OSO2C8F17)3 catalysts dissolve
completely in perfluorocarbon. Based on the 19F NMR
spectroscopic data and GC-MS, no loss of catalyst or per-
fluorodecalin to the organic and water phases can be detected.
But we found that, during repeated nitration reactions, the loss
of fluorous solvent is very serious when using perfluor-
o(methylcyclohexane) (C7F14) as the solvent because it is very
volatile (bp 76 °C). Perfluorodecalin (C10F18, cis- and trans-
mixture) is the best fluorous solvent for nitration (Table 1, entry
4–6).12 This electrophilic aromatic nitration is a triphasic
reaction [top layer is the aromatic compound (organic phase);
middle layer is the nitric acid (water phase); bottom layer is the
perfluorocarbon (fluorous phase)]. Based on the general
concept of fluorous phase chemistry, we also used hexane as a
co-solvent for the nitration of toluene. We found that, upon
heating at 60 °C, the organic phase is miscible with fluorous
phase and the nitration became a biphasic reaction [top layer is
the nitric acid (water phase); bottom layer is the per-
fluorocarbon with aromatic compound (organic phase)]. How-
ever, the yield of nitrated toluene is very similar to that found
with triphasic nitration. It should be emphasized here the ortho,
meta and para distribution is almost same in the cases shown in
Nitration of organic compounds has long been a very active and
rewarding area of research and is the subject of a large body of
literature. Extensive and well documented reviews have been
published by Ingold,1 Olah,2–4 Schofield,5,6 and Ione,7 among
others. Nitrations in manufacturing process require the use of
potent mixtures of concentrated or fuming nitric acid with
sulfuric acid leading to excessive acid waste streams and added
expense. The obvious disadvantages of the commercial manu-
facturing process currently used has led to a substantial effort to
develop viable alternatives, such as using solid-acid catalysts,
+
other sources of NO2 , organic nitrating agents, other acids
replacing sulfuric acid etc. Recently, it was found that
lanthanide(III) triflates (1–10 mol%) [Ln(OTf)3] can catalyze
the nitration of a range of simple aromatic compounds in good
to excellent yield using stoichiometric quantities of 69% nitric
acid, the only by-product being water and the catalyst being
readily recycled by simple evaporation.8 However, this nitration
was carried out in refluxing 1,2-dichloroethane, an environmen-
tally hazardous solvent. In addition, the recovery of the catalyst
from aqueous solution is not an economic process. On the other
hand, perfluorocarbon fluids, especially perfluoro-alkanes have
some unique properties which make them attractive alternatives
for conventional organic solvents.9 They have limited mis-
cibility with conventional organic solvents. Compounds func-
tionalized with perfluorinated groups often dissolve preferen-
tially in fluorous solvents and this property can be used to
extract fluorous components from reaction mixtures.10 Thus, we
attempted to apply fluorous phase separation techniques in
perfluorinated rare earth metal salt catalyzed nitration. With this
method, a practical electrophilic aromatic nitration process can
be established: using 1,2-dichloroethane as a solvent the
recovery of perfluorinated rare earth metal catalysts from
aqueous solution can be avoided. In order to achieve nitration in
the fluorous phase, we prepared perfluorinated rare earth metal
salts [Ln(OSO2C8F17)3, Ln = La, Yb, Sc] as the catalysts11 and
selected perfluorotoluene (C7F8), perfluoro(methylcyclohex-
ane) (C7F14), perfluorohexane (C6F14), and perfluorodecalin
(C10F18, cis- and trans-mixture) as the fluorous solvents. The
nitration of toluene was first carried out in various fluorous
solvents using 60% HNO3 as the nitration reagent in the absence
of halogenated organic solvent and with a catalyst loading of
only 0.05 mol% (Scheme 1). We found that, in general, the
nitrated toluene was isolated in 51–60% at 60 °C. The yields
Table 1 with the ratio p+m+o
= 76+0+24. The control
experiment elucidates that only 10% of nitrated product could
be obtained in the absence of perfluorinated rare earth metal
salts [Ln(OSO2C8F17)3, Ln = La, Yb, Sc] by 60% HNO3. In
Table 1 Nitration of toluene in fluorous phase
Fluorous
solvent
Yield/[%]a
Entry
Lewis acid
Yb(OSO2C8F17 3
Yb(OSO2C8F17 3
Time/h
24
1ab
1
2
)
CF3(CF2)4CF3
56
56
)
24
3
4
5
6
Yb(OSO2C8F17 3
Sc(OSO2C8F17 3
Yb(OSO2C8F17 3
La(OSO2C8F17 3
)
24
24
24
24
52
60
57
40
)
)
)
a Isolated yields based on the nitric acid. b p+m+o = 76+0+24
Scheme 1
994
CHEM. COMMUN., 2002, 994–995
This journal is © The Royal Society of Chemistry 2002

addition, we found that a catalyst loading of only 0.05–0.10
aqueous solution can be avoided; 3) the catalyst loading is only
0.05–0.1 mol% and no loss of catalyst or fluorous solvent
occurs.
mol% was required when using fluorous phase technology,
which is more effective than the 10 mol% of lanthanide(III
)
triflates [Ln(OTf)3] required to catalyze the nitration in a
halogenated solvent such as 1,2-dichloroethane.
We thank the State Key Project of Basic Research (Project
973) (No. G2000048007) and the National Natural Science
Foundation of China (20025206) for financial support. We also
thank the Inoue Photochirogenesis Project (ERATO, JST) for
high mass measurement.
Thus, in order to seek out a practical, useful electrophilic
aromatic nitration process, we decided to use the relatively
cheap and similarly active Yb(OSO2C8F17)3 as a catalyst and
perfluorodecalin (C10F18, cis- and trans-mixture) as the fluor-
ous solvent in a triphasic system for electrophilic aromatic
nitration (Scheme 2).13 The results are shown in Table 2. We
found that, using 60 or 95% nitric acid in the presence of 0.1
mol% of Yb(OSO2C8F17)3, the (Scheme 2, Table 2) electro-
philic aromatic nitration proceeded very well for many
substrates at 60 °C. By simple separation of the fluorous phase
containing only the perfluorinated rare earth metal catalyst, the
nitration can be simply repeated many times without reloading
fluorous solvent and the catalyst. In Table 2, we show that the
yields of nitrated products do not decrease over 5 cycles for
many substrates (Table 2). [The yields shown in Tables 1 and 2
are isolated yields after column chromatography (SiO2).]
Higher product yields are obtained using 95% nitric acid as the
nitrating reagent. The unaccounted for yield is due to the
unconverted substrate.
In conclusion, we have explored a practical, useful electro-
philic aromatic nitration process. By using perfluorodecalin
(C10F18, cis- and trans-mixture) as a fluorous solvent and
Yb(OSO2C8F17)3 as a catalyst, the nitration can be repeated
many times without loss of catalyst. There are three major
environmental benefits from using perfluorinated rare earth
metal salts in the fluorous phase in this electrophilic aromatic
nitration: 1) the nitration process does not require sulfuric acid
and halogenated solvent; 2) the nitration can be repeated many
times simply by separation of the fluorous phase for the next
nitration and the recovery of the employed catalyst from
Notes and references
1 C. K. Ingold, Structure and Mechanism in Organic Chemistry 2nd ed.,
Cornell University Press, Ithaca, New York, 1969. For a survey of the
kyodai nitration, see:(a) M. Matsunaga, Chim. Oggi., 1994, 58; (b) T.
Mori and H. Suzuki, Synlett, 1995, 383; (c) T. Suzuki and R. Noyori,
Chemtracts, 1997, 10, 813; (d) J. H. Ridd, Acta. Chem. Scand., 1998, 52,
11; (e) N. Nonoyama, T. Mori and H. Suzuki, Zh. Org. Khim., 1998, 34,
1591.
2 G. A. Olah and S. J. Kuhn, in Friedel-Crafts and Related Reactions, ed.
G. A. Olah, Wiley-Interscience, New York, 1964, Vol. 2.
3 G. A. Olah, ACS Symp. Series, Vol. 22. ed. F. Albright, Washington DC,
1967, p. 1.
4 G. A. Olah, R. Malhotra and S. C. Narang, Nitration: Methods and
Mechanism, ed. H. Feuer, VCH Publishers, New York, 1989.
5 J. G. Hoggett, R. B. Moodie, J. R. Penton and K. Schofield, Nitration
and Aromatic Reactivity, Cambridge University Press, London, 1971.
6 K. Schofield, Aromatic Nitration, Cambridge University Press, London,
1980.
7 L. V. Malysheva, E. A. Paukshtis and K. G. Ione, Catal. Rev.-Sci. Eng.,
1995, 37, 179.
8 (a) F. J. Waller, A. G. M. Barrett, D. C. Braddock and D. Ramprasad, J.
Chem. Soc., Chem. Commun., 1997, 613; (b) A. G. M. Barrett, D. C.
Braddock, R. Ducray, R. M. McKinnell and F. J. Waller, Synlett, 2000,
57; (c) F. J. Waller, A. G. M. Barrett, D. C. Braddock, R. M. McKinnell
and D. Ramprasad, J. Chem. Soc., Perkin Trans. 1, 1999, 867; (d) F. J.
Waller, A. G. M. Barrett, D. C. Braddock, R. M. McKinnell, A. J. P.
White, D. J. Williams and R. Ducray, J. Org. Chem., 1999, 64, 2910.
9 (a) D. W. Zhu, Synthesis, 1993, 953; (b) E. D. Wolf, G. V. Koten and B.-
J. Deelman, Chem. Soc. Rev., 1999, 28, 37.
10 (a) I. T. Horvath and J. Rabai, Science, 1994, 266, 72; (b) I. T. Horvath,
G. Kiss, R. A. Cook, J. E. Bond, P. A. Stevens, J. Rabai and E. J.
Mozeliski, J. Am. Chem. Soc., 1998, 120, 3133; (c) J. Fawcett, E. G.
Hope, R. D. W. Kemmitt, D. R. Paige, D. R. Russell, A. M. Stuart, D.
J. Cole-Hamilton and M. J. Payne, Chem. Commun., 1997, 1127; (d) D.
P. Curran, Angew. Chem., Int. Ed., 1998, 37, 1175; (e) H. Nakamura, B.
Linclau and D. P. Curran, J. Am. Chem. Soc., 2001, 123, 10119.
11 For the preparation of perfluorinated rare earth metal catalysts
[Ln(OSO2C8F17)3, Ln = La, Yb, Sc], please see: Y. Hanamoto, Y.
Sugimoto, Y. Z. Jin and J. Imanaga, Bull. Chem. Soc. Jpn., 1997, 70,
1241. An excess amount of a lanthanide(III) oxide (99.9% purity) was
added to an aqueous solution of C8F17SO3H (50% v/v) and heated at
boiling for 30 min to 1 h. The mixture was filtered to remove the
unreacted oxide. The water was then removed from the filtrate under
reduced pressure. The resulting hydrate was dried by heating under
vacuum at 180 to 200 °C for 48 h.
Scheme 2
Table 2 Isolated yields of nitration of toluene in fluorous phase for 48 ha
Run
1
2
3
4
5
57b
70c
63d
63e
60
65
60
60
56
70
60
60
54
66
64
64
53
71
54
54
12 The nitration of some phenols and alkyl aryl ethers with dinitrogen
pentoxide (N2O5) in perfluorocarbon solvents has been reported by
Crampton: M. R. Crampton, L. M. Gibbons and R. Millar, J. Chem.
Soc., Perkin Trans. 2, 2001, 1662.
13 Typical reaction procedure: 95% nitric acid (0.5 ml, 12 mmol) was
slowly added into a mixture of Yb(OPf)3 (20 mg, 0.012 mmol), toluene
(2.1 ml, 20 mmol) and perfluorodecalin (cis- and trans-mixture, 1.5 ml).
The mixture was stirred at 60 °C for 24 h. Then, the fluorous layer was
separated for the next nitration. The reaction mixture (organic layer and
water phase) was washed with water (5 ml) and extracted with
dichloromethane (2 3 15 ml). The combined organic layers were dried
over MgSO4. The solvent was removed under reduced pressure and the
residue was purified by column chromatography on silica gel (EtOA-
c+hexane = 1+20) to give the product as a yellowish liquid (1.18 g,
70%).
88f
83
83
80
68
a Isolated yields (%) based on the nitric acid. b 60% HNO3, p+m+o =
76+0+24. c 95% HNO3, p+m+o = 76+0+24. d 95% HNO3. e 95% HNO3,
p+m+o = 60+0+40. f 95% HNO3.
CHEM. COMMUN., 2002, 994–995
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