Evidence for the intracomplex reaction in Gattermann-Koch formylation in superacids: Kinetic and regioselectivity studies

Article abstract of DOI:10.1021/ja9641012

Kinetic and regioselectivity data are reported for the Gattermann-Koch formylation of m-xylene, l-methylnaphthalene, and toluene in HF-SbF₅ and CF₃SO₃H-SbF₅ as a function of SbF₅/substrate molar ratio. The kinetic study for m-xylene formylation in HF-SbF₅ provided crucial evidence in favor of intracomplex reaction via a third-order rate equation, [ArH][ArH₂⁺SbF₆^-][CO], where the formylation electrophile HCO⁺ is generated by CO protonation by the arenium ion. Dependence of regioselectivity on substrate, superacid, and SbF⁵/substrate molar ratio showed that high para regioselectivity stems from intracomplex reaction and the observed regioselectivity reflects the ratio between the intracomplex and the conventional reactions. Comparison in regioselectivity between Gattermann-Koch formylation and Friedel-Crafts formylation with use of HCOF suggested that regioselectivity trends do not reflect the nature of the electrophile but the reaction pathway; the Friedel-Crafts formylation also appears to have intracomplex reaction character.

Full text of DOI:10.1021/ja9641012

5100
J. Am. Chem. Soc. 1997, 119, 5100-5105
Evidence for the Intracomplex Reaction in Gattermann-Koch
Formylation in Superacids: Kinetic and Regioselectivity Studies
Mutsuo Tanaka,*,†, Masahiro Fujiwara,† Qiang Xu,† Yoshie Souma,†
Hisanori Ando,§ and Kenneth K. Laali*,‡
Contribution from Osaka National Research Institute, AIST, 1-8-31, Midorigaoka, Ikeda,
Osaka 563, Japan, Research Institute of InnoVatiVe Technology for the Earth, 9-2, Kizugawadai,
Kizu-cho, Sorakugun, Kyoto 619-02, Japan, and Department of Chemistry, Kent State UniVersity,
Kent, Ohio 44242
ReceiVed NoVember 27, 1996. ReVised Manuscript ReceiVed April 6, 1997X
Abstract: Kinetic and regioselectivity data are reported for the Gattermann-Koch formylation of m-xylene,
1-methylnaphthalene, and toluene in HF-SbF5 and CF3SO3H-SbF5 as a function of SbF5/substrate molar ratio.
The kinetic study for m-xylene formylation in HF-SbF5 provided crucial evidence in favor of intracomplex reaction
via a third-order rate equation, [ArH][ArH2+SbF6-][CO], where the formylation electrophile HCO+ is generated by
CO protonation by the arenium ion. Dependence of regioselectivity on substrate, superacid, and SbF5/substrate
molar ratio showed that high para regioselectivity stems from intracomplex reaction and the observed regioselectivity
reflects the ratio between the intracomplex and the conventional reactions. Comparison in regioselectivity between
Gattermann-Koch formylation and Friedel-Crafts formylation with use of HCOF suggested that regioselectivity
trends do not reflect the nature of the electrophile but the reaction pathway; the Friedel-Crafts formylation also
appears to have intracomplex reaction character.
Introduction
reaction (eq 2) whereby the electrophilic substitution occurs
within the complex formed upon addition of a -complex to
the proelectrophile.9
The electrophilic aromatic substitution reaction is a widely
used classical method to prepare various aromatic compounds.
The conventional reaction, whose mechanism and selectivity
have been extensively investigated by Olah et al.1 and other
groups,1-8 is illustrated in eq 1.
(2)
In eq 2, a protonated aromatic compound ArH2+ acts as an acid
to activate the proelectrophile P to the electrophile E+. It has
been suggested that if aromatic substitution actually occurs
within the complex without separation of the reagents, then the
intracomplex reaction should manifest as a distinct reaction
pathway with special kinetic and mechanistic features. When
the electrophile escapes into the medium and reacts with the
aromatic substrate at some later stage, then eq 2 is reduced to
the conventional eq 1, whose only peculiarity is that the acid
used to activate the proelectrophile is a protonated aromatic
compound. Cacace et al. succeeded in demonstrating this
concept in the gas phase by a combination of mass spectrometric
and radiolytic techniques.9
In a scenario that combines Olah’s concept with Cacace’s
concept, if the electrophile and the aromatic substrate formed
through proton transfer between a proelectrophile and a proto-
nated aromatic compound react extremely fast within the
complex, the intracomplex reaction may influence not only the
kinetic features but also the regioselectivity because the aromatic
compound is protonated para to the substituent under acidic
conditions,10 resulting in the formation of an electrophile at the
para position. The transition intermediate should strongly
resemble a -complex, namely, the para-oriented -complex
(1)
In the conventional aromatic substitution reaction, the forma-
tion and the attack of the electrophile are separated steps. The
electrophile is formed and dispersed in the reaction medium
before the attack on an aromatic compound. However, Cacace
et al. recently proposed an alternative route, the intracomplex
† Osaka National Research Institute.
‡ Kent State University.
§ Research Institute of Innovative Technology for the Earth.
Postdoctoral research fellow in the Laali group (1996-1997).
X Abstract published in AdVance ACS Abstracts, May 15, 1997.
(1) Olah, G. A. Friedel-Crafts and Related Reactions; Wiley-Inter-
science: New York, 1964.
(2) Olah, G. A. Acc. Chem. Res. 1971, 4, 240.
(3) (a) Jensen, F. R.; Brown, H. C. J. Am. Chem. Soc. 1958, 80, 4046.
(b) Olah, G. A.; Tashiro, M.; Kobayashi, S. J. Am. Chem. Soc. 1970, 92,
6369. (c) Olah, G. A.; Hashimoto, I.; Lin, H. C. Proc. Natl. Acad. Sci.
U.S.A. 1977, 74, 4121.
(4) (a) Pedersen, E. B.; Petersen, T. E.; Torssell, K.; Lawesson, S.
Tetrahedron 1973, 29, 579. (b) Kita, Y.; Tohma, H.; Hatanaka, K.; Takeda,
T.; Fujita, S.; Mitoh, S.; Sakurai, H.; Oka, S. J. Am. Chem. Soc. 1994, 116,
3684.
(5) (a) Olah, G. A.; Kobayashi, S. J. Am. Chem. Soc. 1971, 93, 6964.
(b) Olah, G. A.; Kobayashi, S.; Tashiro, M. J. Am. Chem. Soc. 1972, 94,
7448. (c) Olah, G. A.; Kobayashi, S.; Nishimura, J. J. Am. Chem. Soc.
1973, 95, 564.
(6) (a) Olah, G. A.; Lukas, J.; Lukas, E. J. Am. Chem. Soc. 1969, 91,
5319. (b) Olah, G. A.; Melby, E. G. J. Am. Chem. Soc. 1973, 95, 4971. (c)
Olah, G. A.; Nishimura, J. J. Org. Chem. 1974, 39, 1203.
(7) Brown, H. C.; Bolto, B. A.; Jensen, F. R. J. Org. Chem. 1958, 23,
414.
(9) (a) Aschi, M.; Attina, M.; Cacace, F. Angew. Chem., Int. Ed. Engl.
1995, 34, 1589. (b) Aschi, M.; Attina, M.; Cacace, F. J. Am. Chem. Soc.
1995, 117, 12832. (c) Aschi, M.; Attina, M.; Cacace, F. Res. Chem.
Intermed. 1996, 22, 645.
(10) (a) Olah, G. A.; Schlosberg, R. H.; Porter, R. D.; Mo, Y. K.; Kelly,
D. P.; Mateescu, G. D. J. Am. Chem. Soc. 1972, 94, 2034. (b) Olah, G. A.;
Mateescu, G. D.; Mo, Y. K. J. Am. Chem. Soc. 1973, 95, 1865. (c) Olah,
G. A.; Staral, J. S.; Asencio, G.; Liang, G.; Forsyth, D. A.; Mateescu, G.
D. J. Am. Chem. Soc. 1978, 100, 6299.
(8) On the other hand, the difference between meta and ortho-para
regioselectivity is considered to derive from the oxidation potential
difference. Fukuzumi, S.; Kochi, J. K. J. Am. Chem. Soc. 1981, 103, 7240.
S0002-7863(96)04101-7 CCC: $14.00 © 1997 American Chemical Society

Gattermann-Koch Formylation in Superacids
J. Am. Chem. Soc., Vol. 119, No. 22, 1997 5101
Figure 2. Yields of mono- and dialdehyde in 1-methylnaphthalene
formylation with HF-SbF5. The formylation was carried out with HF
(500 mmol) and 1-methylnaphthalene (10 mmol) at 0 °C for 2 h under
20 atm of CO pressure. The symbols O and b represent mono- and
dialdehyde, respectively.
Figure 1. Isomer ratio of monoaldehyde in 1-methylnaphthalene
formylation with HF-SbF5. The formylation was carried out with HF
(500 mmol) and 1-methylnaphthalene (10 mmol) at 0 °C for 2 h under
20 atm of CO pressure. The symbols O and b represent 1-methyl-4-
and 1-methyl-2-naphthaldehyde, respectively.
(eq 3), and high para regioselectivity is expected in ortho-para
regioselective reactions.
(3)
While the high reactivity of the electrophile is necessary for
the intracomplex reaction, the basicity of aromatic compounds
is another significant factor for the intracomplex reaction
resulting in the high para regioselectivity. When the intracom-
plex reaction is predominant, basic aromatic compounds will
show higher para regioselectivity because the electrophile is
produced closer to the aromatic compounds which is not
necessarily the case in the conventional reaction.
Figure 3. Relationships of [ArH] and [HCO+] with the SbF5/m-xylene
molar ratio.
the apparent rate of the Gattermann-Koch formylation.14 In
order to derive the rate equations for m-xylene formylation in
CF3SO3H-SbF5, we applied the following assumptions: (1)
when the SbF5/m-xylene molar ratio is less than 1, the formyl
cation produced by CF3SO3H brings about the formylation and
the role of CF3SO3H‚SbF5 is to protonate m-xylene; and (2)
when the SbF5/m-xylene molar ratio exceeds 1, the formyl cation
produced by CF3SO3H‚SbF5 effects the formylation. The
dependence of the SbF5/m-xylene molar ratio on the m-xylene
and the formyl cation concentrations is shown in Figure 3.14
On the basis of kinetic studies, two second-order reactions and
one pseudo-first-order reaction are obtained, depending on the
SbF5/m-xylene ratio (eq 4).
The Gattermann-Koch formylation11 is a typical electrophilic
substitution reaction with high para regioselectivity.12 In
previous work,13 it was found, however, that the regioselectivity
of 1-methylnaphthalene formylation in HF-SbF5 drastically
changes at the point where the SbF5/1-methylnaphthalene molar
ratio is 1; the isomer ratio of 1-methyl-2-:1-methyl-4-naphthal-
dehyde is 0:1 or 3:7 depending on the SbF5/1-methylnaphthalene
molar ratio (Figure 1). Similarly, the formylation yield changed
drastically at the same point, consistent with the change of the
mechanism as depicted in Figure 2. Such anomalous rate and
regioselectivity changes cannot be explained through a con-
ventional substitution mechanism.
The paper reports the first example of the intracomplex
reaction in the Gattermann-Koch formylation in superacids
showing not only kinetic features but also a regioselectivity
typical of the intracomplex reaction.
Results and Discussion
(4)
Kinetic Study of m-Xylene Formylation. The protonation
equilibrium of aromatic compounds by superacids influences
(11) Gattermann, L.; Koch, J. A. Chem. Ber. 1897, 30, 1622.
(12) (a) Olah, G. A.; Pelizza, F.; Kobayashi, S.; Olah, J. A. J. Am. Chem.
Soc. 1976, 98, 296. (b) Olah, G. A.; Ohannesian, L.; Arvanaghi, M. Chem.
ReV. 1987, 87, 671. (c) Tanaka, M.; Iyoda, J.; Souma, Y. J. Org. Chem.
1992, 57, 2677. (d) Tanaka, M.; Souma, Y. J. Chem. Soc., Chem. Commun.
1991, 1551. (e) Tanaka, M.; Fujiwara, M.; Ando, H.; Souma, Y. J. Org.
Chem. 1993, 58, 3213.
Interestingly, when the SbF5/m-xylene molar ratio is greater than
1, the pseudo-first-order reaction appears. This observation is
clearly a peculiar feature of the Gattermann-Koch formylation
because this means that HCO+CF3SO3-, which should have
(13) Tanaka, M.; Fujiwara, M.; Ando, H.; Souma, Y. J. Chem. Soc.,
Chem. Commun. 1996, 159.
(14) Tanaka, M.; Fujiwara, M.; Ando, H. J. Org. Chem. 1995, 60, 2106.

5102 J. Am. Chem. Soc., Vol. 119, No. 22, 1997
Tanaka et al.
been produced in sufficient concentration to appear in a second-
order rate expression, does not react with m-xylene under these
conditions. If the Gattermann-Koch formylation proceeds
through the intracomplex reaction, its rate equation should be
different from that of the conventional reaction as described in
eq 5.
(5)
Figure 4. Correlation of [CO]o[HF‚SbF5]o([ArH]o - [HF‚SbF5]o) with
[ArCHO]/t. The formylation was carried out with HF (500 mmol), SbF5
(5.5-9.5 mmol), and m-xylene (10 mmol) at 0 °C for 30 s under 20
atm of CO pressure.
However, the two equations differ only by kinetic constant
values, which could not been determined (eq 6).
(6)
In eq 6, KArH and KCO are protonation equilibrium constants in
superacids for ArH and CO, respectively. We previously found
that whereas in the Gattermann-Koch formylation the formyl
cation acts not only as an electrophile but also as a Brønsted
acid,15 formylation predominates over sulfonation under condi-
tions where most arenes are protonated. These observations
suggest that the Gattermann-Koch formylation has a peculiar
mechanism, compatible with that of the intracomplex reaction
eq 2.
Figure 5. Correlation of [CO]o[ArH]o with [ArCHO]/t. The formylation
was carried out with HF (500 mmol), SbF5 (120-200 mmol), and
m-xylene (10 mmol) at 0 °C for 15 s under 20 atm of CO pressure.
complex similar, for example, to the complex of the tropylium
cation with aromatic compounds.16
In CF3SO3H-SbF5, the formylation is brought about by CF3-
SO3H and controlled by protonation of m-xylene with CF3-
SO3H‚SbF5 when the SbF5/m-xylene molar ratio is less than
1.14 On the other hand, in HF, no formylation occurs in the
absence of SbF5,12d,e namely, it is effected by HF‚SbF5 under
all conditions. Therefore, the formylation rate equation in
HF-SbF5 is mechanistically informative especially when the
SbF5/m-xylene molar ratio is less than 1. As for formylation
of m-xylene in CF3SO3H-SbF5,14 we applied the follow-
ing assumptions: (1) when the SbF5/m-xylene ratio is less than
1, the concentration of m-xylene protonated by HF‚SbF5,
[ArH2+SbF6-], corresponds to the original concentration of
added SbF5, [HF‚SbF5]o; and (2) when the SbF5/m-xylene molar
ratio exceeds 1, the concentration of [ArH2+SbF6-] is the orig-
inal concentration of added m-xylene, [ArH]o. The concentra-
tion of CO, [CO], was assumed to be the original concentration
of CO, [CO]o, because of the extremely low conversion into
HCO+.14 The results are shown in Figures 4 and 5. Surpris-
ingly, the third-order rate equation, [ArH]2[HCO+SbF6-], ap-
peared when the SbF5/m-xylene molar ratio was less than 1 as
shown in Figure 4. Since it would be difficult to explain why
two neutral aromatic molecules are necessary for the formyla-
tion, and a trimolecular collision is improbable in solution, the
equation should be presented as [ArH][ArH2+SbF6-][CO] (eq
(7)
This equation shows that the [ArH]/[ArH2+SbF6-] complex
produces the formyl cation [HCO+SbF6-], which reacts within
the complex, according to the intracomplex mechanism, when
the SbF5/m-xylene molar ratio is less than 1. On the other hand,
when the SbF5/m-xylene molar ratio exceeds 1, the second-order
formylation rate equation, [ArH][HCO+SbF6-], is observed as
expected. However, it remained to be ascertain whether the
intracomplex mechanism holds at SbF5/m-xylene molar ratios
greater than 1.
Regioselectivity and Relative Rate of the Intracomplex and
the Conventional Formylation. The high para regioselectivity
of the Gattermann-Koch formylation in HF-SbF5 (Figure 1)
is clearly caused by the intracomplex reaction when the SbF5/
1-methylnaphthalene molar ratio is less than 1. Probing the
reaction under conditions where the SbF5/1-methylnaphthalene
molar ratio was 1 provided an important clue. Monoaldehyde
(16) (a) Feldman, M.; Winstein, S. J. Am. Chem. Soc. 1961, 83, 3338.
(b) Feldman, M.; Graves, B. G. J. Phys. Chem. 1966, 70, 955. (c) Dauben,
H. J., Jr.; Wilson, J. D. J. Chem. Soc., Chem. Commun. 1968, 1629. (d)
Takahashi, Y.; Sankararaman, S.; Kochi, J. K. J. Am. Chem. Soc. 1989,
111, 2954. (e) Kochi, J. K. Acta Chem. Scand. 1990, 44, 409.
-
7) according to eq 6, where ArH and ArH2+SbF6 form a
(15) Tanaka, M.; Fujiwara, M.; Ando, H. J. Org. Chem. 1995, 60, 3846.

Gattermann-Koch Formylation in Superacids
J. Am. Chem. Soc., Vol. 119, No. 22, 1997 5103
a
Table 1. Formylation of Toluene in HF-SbF5
SbF5/substrate
molar ratio
yield (%)
ortho (%)
meta (%)
para (%)
0.5
1
2
4
8
34
78
90
94
94
96
2.9
3.2
6.1
10.7
13.1
22.2
0.3
0.6
0.6
0.6
0.6
0.5
96.8
96.2
93.3
88.7
86.3
77.3
20
a The formylation was carried out with HF (500 mmol) and toluene
(10 mmol) under 20 atm of CO pressure at 0 °C for 1 h.
intracomplex reaction by CF3SO3H‚SbF5 to produce only
1-methyl-4-naphthaldehyde. When the SbF5/1-methylnaphtha-
lene molar ratio was greater than 1, the formylation by CF3-
SO3H‚SbF5 proceeded through both the intracomplex and the
conventional mechanisms. Hence, para regioselectivity de-
creased with an increase in the SbF5/1-methylnaphthalene molar
ratio, reflecting the increased rate of the conventional reaction.
These results suggest that the regioselectivity in the formylation
reflects the ratio between the intracomplex and the conventional
reactions.
Figure 6. Isomer ratio of monoaldehyde in 1-methylnaphthalene
formylation with CF3SO3H-SbF5. The formylation was carried out with
CF3SO3H (200 mmol) and 1-methylnaphthalene (10 mmol) at 0 °C for
2 h under 20 atm of CO pressure. Dialdehyde was not formed under
these conditions. The symbols O and b represent 1-methyl-4- and
1-methyl-2-naphthaldehyde, respectively.
In the formylation of 1-methylnaphthalene, the regioselectivity
changes more drastically in HF-SbF5 than in CF3SO3H-SbF5.
The different regioselectivity trends in HF-SbF5 and CF3-
SO3H-SbF5 seem to derive from the difference in the nature
of the superacid. Whereas regular HF is weaker than CF3SO3H,
HF-SbF5 is one of strongest superacids known.17 Therefore,
1-methylnaphthalene forms a more stable -complex in HF-
SbF5 than in CF3SO3H-SbF5, which can be a critical factor in
controlling the ratio between the intracomplex and the conven-
tional reactions. The switch of the formylation mechanism from
the intracomplex to the conventional reaction as a function of
the superacid/substrate molar ratio may reflect the stability of
the -complex, because the rate of the intracomplex reaction is
adversely affected by an increase in the stability of the
-complex.9 This corresponds to the result of the 1-methyl-
naphthalene formylation in HF-SbF5, which leads to the most
stable -complex, causing a more drastic change in the
formylation mechanism than in CF3SO3H-SbF5.
was obtained in 90% yield and 94% para regioselectivity when
the SbF5/1-methylnaphthalene molar ratio was just above 1
within experimental error ((5%) as shown in Figures 1 and 2,
strongly suggesting that formylation proceeded via the intrac-
omplex reaction with the high para regioselectivity even when
the SbF5/1-methylnaphthalene molar ratio was greater than 1.
On the other hand, it is clear that the conventional formylation
shows both para and ortho regioselectivities (eq 8).
(8)
In order to clarify this inference, we examined whether a
lower basicity aromatic compound, toluene, exhibits a similar
regioselectivity change in HF-SbF5. Formylation of toluene
at low temperature in HF-SbF5/SO2ClF shows low regio-
selectivity.12a The formylation of toluene in HF-SbF5 in the
-78 to 0 °C range displayed no regioselectivity change, but
changed depending on the SbF5/toluene molar ratio as shown
in Table 1. As expected, the regioselectivity change, reflecting
the transition from the intracomplex to the conventional
mechanism, was gradual, being observed when the SbF5/toluene
ratio largely exceeded 1. On the other hand, at SbF5/substrate
ratios less than 1, toluene showed less para regioselectivity than
1-methylnaphthalene. This trend, which is in contrast with that
of the conventional electrophilic aromatic substitutions, is
consistent with the specific features of the intracomplex reaction
as mentioned in the introduction. These results clearly reflect
that the basicity of toluene is significantly less than that of
1-methylnaphthalene.
In order to investigate the ratio between the intracomplex
and the conventional reactions, the formylation of 1-methyl-
naphthalene in CF3SO3H-SbF5 was investigated because it
seems to proceed via the intracomplex reaction showing high
para regioselectivity when the SbF5/1-methylnaphthalene molar
ratio is around 1, especially when the formylation is described
by the pseudo-first-order reaction. The regioselectivity change
also appeared in the formylation of 1-methylnaphthalene in CF3-
SO3H-SbF5 as depicted in Figure 6. As expected, the para
regioselectivity showed a maximum at a SbF5/1-methylnaph-
thalene molar ratio of 1. This trend devotes simultaneous
operation of the intracomplex and the conventional pathways.
When the SbF5/1-methylnaphthalene molar ratio was less than
1, formylation by CF3SO3H proceeded through both mechanisms
whereby formylation by CF3SO3H‚SbF5 proceeded through the
intracomplex mechanism. Therefore, the para regioselectivity
increased with the SbF5/1-methylnaphthalene molar ratio,
reflecting the increased extent of the intracomplex reaction by
CF3SO3H‚SbF5. When the SbF5/1-methylnaphthalene molar
ratio was 1, formylation proceeded exclusively through the
Friedel-Crafts (HCOF) and Gattermann-Koch (CO)
Formylations. The existence of a dication as the true electro-
phile in electrophilic aromatic substitutions has been proposed
in cases where higher acidity Ho increases the reaction rate.18
Taking into account the protonation equilibrium of aromatic
(17) (a) Gillespie, R. J.; Liang, J. J. Am. Chem. Soc. 1988, 110, 6053.
(b) Olah, G. A.; Prakash, G. K. S.; Sommer. J. Superacids; Wiley-
Interscience: New York, 1985; Chapter 1.

5104 J. Am. Chem. Soc., Vol. 119, No. 22, 1997
Tanaka et al.
Table 2. Friedel-Crafts and Gattermann-Koch Formylation of
Table 3. Friedel-Crafts Formylation of Toluenea
1-Methylnaphthalenea
SbF5/substrate
SbF5/substrate
temp
yield of
isomer ratio of
molar ratio
yield (%)
ortho (%)
meta (%)
para (%)
molar ratio reagent (°C) time aldehyde (%) 2-:4-aldehyde
0.5
1
1.5
1.6
1.8
2
4
8
20
22
28
26
20
25
53
71
90
94
33.3
35.5
36.5
25.7
17.7
6.8
9.3
11.4
20.1
2.1
2.1
2.3
2.2
1.8
0.7
0.7
0.6
0.5
64.6
62.4
61.2
72.1
80.5
92.5
90.0
88.0
79.4
1
HCOF
HCOF
HCOF -40 1 h
HCOF -40 1 h
CO
CO
CO
0
0
1 h
1 h
15
45
33
50
24
12
13
7:93
6:94
6:94
1.25
1.25
2
1
1.25
1.25
6:94
0
0
2 h
10 min
0:100
32:68
36:64
-40 2 h
a The formylation was carried out with HF (500 mmol) and
1-methylnaphthalene (10 mmol) under 20 atm of CO pressure or with
HCOF (80 mmol).
a The formylation was carried out with HF (500 mmol), toluene (10
mmol), and HCOF (80 mmol) at 0 °C for 1 h.
compounds in superacids, in the HF-SbF5 system the formyl
cation could in principle be a mono- or a dication, depending
on the SbF5/1-methylnaphthalene molar ratio (eq 9).
higher para regioselectivity than the Gattermann-Koch formyl-
ation. Furthermore, when the SbF5/1-methylnaphthalene molar
ratio was greater than 2, the Friedel-Crafts formylation did not
occur at all at 0 °C in HF-SbF5. These results imply that the
Friedel-Crafts formylation proceeds via the formyl cation from
the reaction of HCOF with the -complex, namely, via the
intracomplex route because neutral HCOF is far more accessible
to a cationic charged -complex than the positively charged
HCO+ (eq 10).
(9)
If the regioselectivity change illustrated in Figure 1 is derived
from the difference in the nature of the formyl cation (mono-
or dication), our data (Figure 1) imply that the regioselectivity
at the para position of 1-methylnaphthalene should be high for
the monocation but low for the dication.
In order to clarify whether the difference in the nature of
formyl cation electrophile causes the regioselectivity change of
the Gattermann-Koch formylation, the reaction of 1-methyl-
naphthalene with HCOF, the Friedel-Crafts formylation, was
carried out in HF-SbF5 and its regioselectivity was compared
with that of the Gattermann-Koch formylation. The Friedel-
Crafts formylation clearly does not involve CO, but the formyl
cation produced by ionization of HCOF.19 These results
revealed a significant difference in the regioselectivity as shown
in Table 2. In the case of the Friedel-Crafts formylation, the
regioselectivity was constant regardless of the SbF5/1-methyl-
naphthalene molar ratio, even at values as high as 2, where the
formyl cation can be further protonated (protosolvated) to be
dicationic. Therefore, we concluded that the regioselectivity
change is not caused by the change in the nature of the
electrophile.20 This conclusion is also supported by the result
of the 1-methylnaphthalene formylation in CF3SO3H-SbF5 in
Figure 6. The regioselectivity change under conditions where
the SbF5/1-methylnaphthalene molar ratio is less than 1 cannot
be explained in terms of the nature of the formyl cation.
In the formylation of 1-methylnaphthalene in HF-SbF5, the
Friedel-Crafts reaction seems to proceed via the conventional
route, as does the Gattermann-Koch formylation, when the
SbF5/1-methylnaphthalene molar ratio is greater than 1. Similar
(10)
Should the Friedel-Crafts formylation have the same intra-
complex nature as the Gattermann-Koch formylation, the
regioselectivity should show the specific features of the intra-
complex reaction and would be controlled by the stability of
the protonated aromatic compounds.
In order to clarify the above inference, the Friedel-Crafts
formylation of a lower-basicity compound, toluene, was inves-
tigated. When the formylation was carried out in HF-SbF5,
para regioselectivity was low compared with the 1-methyl-
naphthalene formylation as shown in Table 3, consistent with
the specific regioselectivity trends of the intracomplex reaction.
On the other hand, the Friedel-Crafts formylation of toluene
showed quite a different trend compared with that of 1-meth-
ylnaphthalene when the SbF5/toluene molar ratio was greater
than 2.21 Under these conditions, the regioselectivity of the
toluene formylation shows a similar trend as that of the
Gattermann-Koch formylation. The transition of the formyl-
ation mechanism from the Friedel-Crafts to the Gattermann-
Koch formylation is suggested because of higher reactivity of
toluene compared to 1-methylnaphthalene, which is a specific
feature of the intracomplex reaction.9
regioselectivity is expected in both formylations, because both
-
involve the same reactive species, HCO+SbF6
. However,
different regioselectivities were observed as shown in Table 2.
Under these conditions, Friedel-Crafts formylation showed
Conclusions
(18) (a) Olah, G. A.; Rasul, G.; Aniszfeld, R.; Prakash, G. K. S. J. Am.
Chem. Soc. 1992, 114, 5608. (b) Olah, G. A. Angew. Chem., Int. Ed. Engl.
1993, 32, 767. (c) Saito, S.; Sato, Y.; Ohwada, T.; Shudo, K. J. Am. Chem.
Soc. 1994, 116, 2312. (d) Saito, S.; Ohwada, T.; Shudo, K. J. Am. Chem.
Soc. 1995, 117, 11081. (e) Olah, G. A.; Rasul, G.; York, C.; Prakash, G.
K. S. J. Am. Chem. Soc. 1995, 117, 11211. (f) Ohwada, T.; Yamazaki, T.;
Suzuki, T.; Saito, S.; Shudo, K. J. Am. Chem. Soc. 1996, 118, 6220.
(19) In control experiments, HCOF was decomposed to HF and CO
immediately in HF, and the Gattermann-Koch formylation did not occur
under atmospheric CO pressure under these conditions.
Kinetics and regioselectivity evidence in the superacid-
catalyzed Gattermann-Koch formylation point to the intra-
complex electrophilic aromatic substitution character. The
significant feature of the intracomplex reaction in regioselectivity
is that the regioselectivity reflects both the structure and the
stability of the arenium ion as a reaction precursor. The
observation of the intracomplex reaction resulting in the high
para regioselectivity in the Gattermann-Koch formylation is
(20) The kinetic study for the formylation shows that HCO+ is the
electrophile under these conditions, however, possible involvment of dication
HCOH2+ cannot be excluded.
(21) In control experiments, the elimination of formyl group was not
observed under the same conditions.

Gattermann-Koch Formylation in Superacids
J. Am. Chem. Soc., Vol. 119, No. 22, 1997 5105
a Hastelloy autoclave (100 mL) equipped with a Hastelloy magnetic
stirrer bar under temperature control. The autoclave was sealed, and
CO (20 atm) was introduced with vigorous stirring. After the raction
was over, the autoclave was depressurized and opened. The reaction
mixture was quenched with ice water and extracted with benzene.
Friedel-Crafts Formylation Procedures. HCOF (80 mmol, 3.84
g), which was prepared from KHF2, HCOOH, and C6H5COCl according
to the literature,23 was added to a solution of substrate (10 mmol) with
HF and SbF5 in a Teflon round-bottom flask (300 mL) under
temperature control with vigorous stirring. After 1 h, the reaction
mixture was quenched with ice water and extracted with benzene.
in all probability a consequence of the very short lifetime of
the formyl cation in superacids under the reaction conditions
in solution.
Experimental Section
All materials were of the highest available purity and used without
further purification. HF and CF3SO3H contained 0.1 mol and 5 mol
% H2O, respectively. H2O was considered to form H2O‚SbF5 quan-
titatively as an inert additive. The identification of products was
performed by NMR (1H-, 13C-NMR, H-H COSY, C-H COSY, and
COLOC) and mass spectra after separation by distillation, recrystalli-
zation, and HPLC. The yields were determined by GC, and the isomer
distributions were determined by GC and NMR.
JA9641012
(22) The Koch-Haaf carboxylation was negligible because only traces
of carboxylic acids were detected.
(23) Olah, G. A.; Kuhn, S. J. Chem. Ber. 1956, 89, 866.
Gattermann-Koch Formylation Procedures.22 Substrate (10
mmol) was added to a solution of Lewis acids with HF or CF3SO3H in