Counterion effects in indium-catalysed aromatic electrophilic substitution reactions

Article abstract of DOI:10.1016/S0040-4039(02)00931-0

Indium(III) triflamide (In(NTf₂)₃) has been prepared in high yield and has been demonstrated to be an efficient, recoverable catalyst for a range of aromatic electrophilic substitution reactions. When compared to other indium(III) complexes, anomalous reactivities suggest a non-innocent role for the counterion in the studied processes.

Full text of DOI:10.1016/S0040-4039(02)00931-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4789–4791
Counterion effects in indium-catalysed aromatic electrophilic
substitution reactions
a,
a
b
Christopher G. Frost, * Joseph P. Hartley and David Griffin
a
Department of Chemistry, University of Bath, Calverton Down, Bath BA2 7AY, UK
b
Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6ET, UK
Received 4 March 2002; revised 29 April 2002; accepted 13 May 2002
Abstract—Indium(III) triflamide (In(NTf ) ) has been prepared in high yield and has been demonstrated to be an efficient,
2
3
recoverable catalyst for a range of aromatic electrophilic substitution reactions. When compared to other indium(III) complexes,
anomalous reactivities suggest a non-innocent role for the counterion in the studied processes. © 2002 Elsevier Science Ltd. All
rights reserved.
The efficient preparation of diversely functionalised
aromatics has traditionally relied on the use of stoichio-
metric promoters of electrophilic substitution such as
aluminium(III) chloride with the associated purification
highly active ytterbium(III) and scandium(III) triflides
which promote the nitration of activated and deacti-
vated aromatics. Although never previously tested, we
8
supposed that indium salts should be effective catalysts
1
3+
problems. More recently, efficient catalytic protocols
given the charge-to-size ratio of 3.75 (r =0.80 A)
,
have emerged including the use of Fe(III) exchanged
along with their established Lewis acidity in aqueous
solvents.
2
3
4
montmorillonite clay, zeolites, bismuth(III) salts,
5
scandium and lanthanide(III) salts. In previous work
we have demonstrated that commercially available indi-
um(III) triflate functions as an efficient Lewis acid
At the outset of the study we examined the nitration of
selected aromatics with different indium salts to vali-
date the importance of counterion (Table 1). In a
typical experiment we heated a mixture of aromatic (3
mmol), 69% nitric acid (1 equiv.) and indium catalyst
(10 mol%) in 1,2-dichloroethane (5 ml) to reflux for
6–18 h. After dilution with water the organic phase was
separated, dried and evaporated under pressure to
afford the nitration product which could be purified by
either recrystallisation or column chromatography. The
indium salt could be recovered by evaporation of the
aqueous phase and used in subsequent reactions with
no significant loss of activity.
6
catalyst at low catalyst loadings. In this communica-
tion we wish to report the remarkable consequences of
changing the counterion to the less coordinating tri-
flamide anion in a range of aromatic electrophilic sub-
stitution processes.
The new indium complex, In(NTf ) , was easily pre-
2
3
pared by the reaction of indium oxide (In O ) with
2
3
bis(trifluoromethanesulfonyl)imide (Tf NH). Thus,
2
heating an aqueous solution of In O and Tf NH at
2
3
2
reflux for 24 h provided In(NTf ) in an almost quanti-
2
3
tative yield after work-up and drying. The procedure
was based on previous reports for the preparation of
In the absence of catalyst a slow background reaction
afforded less than 10% of nitration product. It was
pleasing to note that indium(III) triflate and indium-
(III) triflamide were active catalysts for nitration reac-
7
Sc(NTf ) . We decided to test the efficacy of In(NTf )
2
3
2 3
in the clean, catalytic nitration of aromatics where the
Lewis acid serves as a replacement for sulfuric acid and
the only by-product is water (Scheme 1).
This important area is led by the excellent contributions
from Barrett and Braddock who have revealed recy-
clable catalysts such as lanthanide(III) triflates and the
*
Corresponding author. Tel.: +44(0)1225 386142; fax: +44(0)1225
86231; e-mail: c.g.frost@bath.ac.uk
Scheme 1.
3
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00931-0

4
790
C. G. Frost et al. / Tetrahedron Letters 43 (2002) 4789–4791
Table 1. Evaluation of indium catalysts in aromatic nitration
Entry
Catalyst
Aromatic
Time (h)
Yield (%)
Isomer ratio
1
2
3
4
5
6
7
8
9
InCl3
Toluene
Toluene
Toluene
m-Xylene
6
6
6
6
6
18
18
18
18
18
B5
99
99
95
99
89
98
93
B5
31
–
In(OTf)3
In(NTf2)3
In(OTf)3
In(NTf2)3
In(OTf)3
In(NTf2)3
In(NTf2)3
In(OTf)3
In(NTf2)3
50:7:43 (o:m:p)
48:7:45 (o:m:p)
14:86 (2-NO :4-NO )
14:86 (2-NO :4-NO )
33:0:67 (o:m:p)
39:0:61 (o:m:p)
33:0:67 (o:m:p)
–
2
2
m-Xylene
2
2
Bromobenzene
Bromobenzene
Chlorobenzene
2-Nitrotoluene
2-Nitrotoluene
1
0
35:65 (2,4-NO :2,6-NO )
2 2
tions including the efficient functionalisation of aryl
carboxylic acids (Scheme 2). The catalyst loading
(
In(NTf ) ) could be lowered to 1 mol% in the nitration
2 3
of bromobenzene affording a 47% isolated yield of
product. The isolated yields for different aromatic com-
pounds could be correlated to Hammett coefficients
and catalyst counterion. Thus, electron-rich aromatics
like toluene and m-xylene were easily nitrated with both
In(OTf) and In(NTf ) , whilst much lower reactivity
3
2 3
was observed for 2-nitrotoluene. The difference in
activity reveals the crucial and complex role of the
counterion. Although proven to be an excellent Lewis
acid in aqueous systems, indium(III) chloride does not
promote the reaction. A similar lack of activity using
lanthanide(III) chlorides is postulated to be as a result
of the inability of the chloride ion to transport the
nitronium ion into the organic phase where the reaction
8
occurs. If this is indeed the case the increased solubility
of the nitronium triflamide salt as well as acidity con-
siderations contribute to the observed superior activity
9
of In(NTf ) .
2
3
As shown in Scheme 3, In(NTf ) is a superior catalyst
2
3
for the acetylation of electron-rich aromatics with ace-
1
0
tic anhydride. In these examples we presume that the
weakly coordinating triflamide anion leads to enhanced
Scheme 3.
Lewis acidity via a coordination complex. In similar
7
reactions Sc(NTf2)3 is more active than Sc(OTf)3.
However, in more demanding processes such as the
benzoylation and sulfonylation of weakly activated or
deactivated aromatics we see a pronounced reversal in
catalytic performance (with benzoyl and sulfonyl chlo-
rides). The success of In(OTf) may be accounted for by
3
−
−
a mechanism involving a ligand exchange (TfO /Cl ) at
the indium atom affording an acyl triflate (RCOOTf) or
Scheme 2.
mixed sulfonic anhydride (ArSO OTf) in situ which are
2

C. G. Frost et al. / Tetrahedron Letters 43 (2002) 4789–4791
4791
much more reactive species and thus allow the func-
tionalisation of weakly activated or deactivated aromat-
ics. In the case of acid anhydrides no exchange occurs
invoking a method of activation based solely on coordi-
nation. This is confirmed in the reaction of benzene
with benzoic anhydride where less than 10% of benzo-
phenone product is isolated in the presence of In(OTf)3.
This mechanism was first suggested by Dubac for bis-
muth-catalysed Friedel–Crafts reactions and recently
Taylor, R. Electrophilic Aromatic Substitution; Wiley-
Interscience: Chichester, 1990.
2. Choudary, B. M.; Sreenivisa Chwdari, N.; Lakshmi Kan-
tam, M.; Kannan, R. Tetrahedron Lett. 1999, 40, 2859.
3. Smith, K.; Ewart, G. M.; Randles, K. R. J. Chem. Soc.,
Perkin Trans. 1 1997, 1085.
4. (a) R e´ pichet, S.; Le Roux, C.; Dubac, J. J. Org. Chem.
1999, 64, 6479; (b) R e´ pichet, S.; Le Roux, C.; Dubac, J.
Tetrahedron Lett. 1999, 40, 9233; (c) Marqui e´ , J.; Lapor-
tiere, A.; Dubac, J.; Roques, N.; Desmurs, J.-R. J. Org.
Chem. 2001, 66, 421.
5. (a) Kawada, A.; Mitamura, S.; Kobayashi, S. Chem.
Commun. 1993, 1157; (b) Kawada, A.; Mitamura, S.;
Kobayashi, S. Synlett 1994, 545; (c) Kobayashi, S.;
Nagayama, S. J. Am. Chem. Soc. 1998, 120, 2985.
6. (a) Ali, T.; Chauhan, K. K.; Frost, C. G. Tetrahedron
Lett. 1999, 40, 5621; (b) Chauhan, K. K.; Frost, C. G.;
Love, I.; Waite, D. Synlett 1999, 1743; (c) Chauhan, K.
K.; Frost, C. G. J. Chem. Soc., Perkin Trans. 1 2000, 18,
3015; (d) Chapman, C. J.; Frost, C. G.; Hartley, J. P.;
Whittle, A. J. Tetrahedron Lett. 2001, 42, 773; (e) Frost,
C. G.; Hartley, J. P.; Whittle, A. J. Synlett 2001, 830.
11
elucidated in an excellent review. We suggest that the
increased acidity of HNTf relative to TfOH precludes
2
−
−
any NTf /Cl exchange and activation can only occur
2
12
by coordination.
In conclusion, we have presented a new indium catalyst
for aromatic electrophilic substitution reactions. In dif-
ferent substitution processes the physical properties of
the counterion have been shown to dictate catalytic
activity. A better understanding of the function of
counterions in other catalytic systems may lead to
improved activity and the discovery of new organic
transformations.
7
. (a) Ishihara, K.; Kubota, M.; Yamamoto, H. Synlett
1996, 265; (b) Ishihara, K.; Karumi, Y.; Kubota, M.;
Acknowledgements
Yamamoto, H. Synlett 1996, 839.
. For an excellent account of this work see: Braddock, C.
8
Green Chem. 2001, G26–G32 and references cited therein.
We would like to thank Syngenta for the provision of a
CASE award to J.P.H. C.G.F. thanks Astra-Zeneca for
a generous award from their strategic research fund and
Pfizer for further funding.
9. Nitronium triflamide is a known compound: Foropoulos,
J., Jr.; Desmarteau, D. D. Inorg. Chem. 1984, 23, 3720.
10. Other electron-rich aromatics including toluene, m-xylene
and mesitylene were acetylated in over 90% isolated
yields under identical conditions.
11. Le Roux, C.; Dubac, J. Synlett 2002, 181.
References
12. Tf NH is a stronger acid than TfOH: Koppel, I. A.; Taft,
2
R. W.; Anvia, F.; Zhu, S.-Z.; Hu, L.-Q.; Sung, K. S.;
DesMarteau, D. D.; Yagupolskii, L. M.; Yagupolskii, Y.
L.; Ignat e´ v, N. V.; Kondratenko, N. V.; Volkonskii, A.
Y.; Vlasov, V. M.; Notario, R.; Maria, P.-C. J. Am.
Chem. Soc. 1994, 116, 3047.
1
. (a) Olah, G. A. Friedel–Crafts Chemistry; Wiley-Inter-
science: New York, 1973; (b) Heaney, H. In Comprehen-
sive Organic Synthesis, Trost, B. M., Ed.; Pergamon
Press: Oxford, 1991; Vol. 2, Chapter 2, pp. 733–752; (c)