New Catalytic Properties of Iron Porphyrins
J. Am. Chem. Soc., Vol. 120, No. 48, 1998 12529
reactions may be (reduction of oximes to aldehydes, direct
reaction between aldehydes and dithionite, oxidation of iron(II)
by air traces, ...), they consume electrons and explain why excess
reductant is necessary for completion of aldoxime dehydration.
The mechanism that was postulated for cytochrome P450-
catalyzed dehydration of aldoximes involves the formation of
a 442 nm absorbing P450-aldoxime complex as a key
intermediate.4 It was proposed that this complex is derived from
the binding of the nitrogen atom of aldoximes to P450 Fe(II).
This proposition was based on the position of its Soret peak,
which is similar to those of complexes between P450 Fe(II)
and nitrogen-containing ligands, and on stereochemical data
showing that only Z-aldoximes form such 442 nm absorbing
complexes. Here we show that aldoximes readily bind to iron(II)
porphyrins with formation of Fe(II)(porphyrin)(aldoxime)2
complexes in which aldoxime binds to the iron via its nitrogen
atom. These data give a firm basis for the structure proposed
for P450-aldoxime complexes and describe the first example
of iron-aldoxime complexes exhibiting such a coordination
mode.11
Figure 5. Intramolecular acid catalysis possibly involved in aldoxime
dehydration catalyzed by iron(II) [meso-(ortho-carboxyphenyltriphenyl)-
porphyrin].
Figure 6. Possible mechanism for iron(II) porphyrin-catalyzed dehy-
Efficient model systems for aldoxime dehydration require the
following features: (i) the use of electron-rich iron porphyrin
catalysts (see Table 3), (ii) the presence of a carboxylic acid,
as shown in Table 3 and from data obtained with Fe(TPP)
bearing a COOH ortho substituent on a meso-phenyl group, and
(iii) the presence of an electron-donating axial ligand of the
iron, as shown by the spectacular increase of the reaction rate
when using MP-11 instead of iron protoporphyrin(IX) as
catalysts. On the basis of these results, it seems that an ideal
catalyst for aldoxime dehydration would be based on an
electron-rich iron(II) porphyrin involving an electron-donating
axial ligand and a free axial binding position and, in close
proximity to the iron center, an acid cocatalyst and a site of
specific recognition and binding for the aldoxime. This may be
the case of some cytochromes P450 which have a very electron-
rich cysteinate proximal ligand of the iron and, on the distal
side of the heme, an acid residue from the protein and a
hydrophobic protein site for aldoxime binding. This should occur
in the cytochrome P450 responsible for the dehydration of an
aldoxime intermediate involved in the biosynthesis of dhurrin
from L-tyrosine (eq 2).5
With reference to the possible mechanisms of aldoxime
dehydration by iron(II) porphyrins and by cytochromes P450,
it is important to understand the origin of the activation of
aldoximes toward dehydration by the iron(II) porphyrins. In view
of the fact that electron-donating substituents on the porphyrin
ring and electron-donating axial ligands strongly favor aldoxime
dehydration, it seems that iron(II) activates bound aldoxime by
increasing the electron density in the CdN-OH moiety.
Accumulation of a partial negative charge on the CdN carbon
in the transition state would then favor the departure of the OH
group of aldoxime (Figure 6). This departure should be greatly
assisted by protonation of the OH group by an acid cocatalyst,
in agreement with the spectacular effect of the COOH group of
carboxylic acids added in excess in the medium, or introduced
in close proximity to the iron on a meso-aryl porphyrin
substituent (Figure 5). The species that would be generated by
loss of the OH group should have a very acidic hydrogen atom
on the carbon bearing the nitrogen atom, because of its
â-position relative to positively charged iron (Figure 6). It should
dration of aldoximes.
be very easily removed by any weak base present in the medium
(pyrrole nitrogens are well located and possible candidates for
this reaction), in a fast step leading to the nitrile product and
regenerating the iron(II) porphyrin catalyst.
This type of activation of the aldoxime is analogous to that
described for pentammineruthenium(II) ions, capable of dehy-
drating aldoximes and of eliminating alcohols from the corre-
sponding oxime ethers, for whom Ru 4d f N(π*) back-bonding
was evoked as a mechanistic explanation.12 In the case of Ru(II),
the nitrile formed has a good affinity for the metal center and
so the complex [(H3N)5Ru(NCR)]2+ is obtained in a stoichio-
metric reaction.
Whatever its detailed mechanism may be, this reaction of
aldoxime dehydration illustrates the potential of iron porphyrins
as catalysts for new reactions very different from the redox
transformations for which they are well-known.
Experimental Section
General Aspects. UV-visible spectra were recorded on a Cary 210
1
spectrophotometer. H NMR spectra were recorded on a Bruker WN
250 MHz. Mass spectra were recorded in the laboratory of Prof. J. C.
Tabet at the Universite´ Paris VI. Elemental analyses were performed
by the Service de Microanalyze du CNRS at Gif-Sur-Yvette, France.
GC analysis was carried out with an Intersmat IGC 120 FL with a
filled glass column (10% FFAP on a WAW 80/100 chromosorb mesh).
Solvents were obtained from SDS (France) (synthesis quality) and used
as obtained for catalysis experiments.
The aldoximes used (acetaldoxime, n-pentanaldoxime, n-heptanal-
doxime) were prepared by literature methods13 from the correspondingly
aldehydes, which were obtained from the Aldrich chemical company,
and the purity of the aldoximes was verified by 1H NMR. Normal
preparations gave Z:E isomer mixtures with the Z isomer predominating
(75% to 95%). GC calibration for catalysis studies was performed by
using bromobenzene as an internal standard for n-pentanaldoxime,
n-pentanonitrile, and n-pentanal, and iodobenzene in the case of the
(12) (a) Guengerich, C. P.; Schug, K. Inorg. Chem. 1983, 22, 1401-
1402. (b) Geno, M. J. K.; Dawson, J. H. Inorg. Chem. 1984, 23, 509-510.
Os(II) complexes were also described to catalyze the dehydration of
aldoximes into nitriles: Daniel, T.; Knaup, W.; Dziallas, M.; Werner, H.
Chem. Ber. 1993, 126, 1981-1993.
(11) For other modes of coordination of oximes to iron complexes in
general, see: King, R. B.; Douglas, W. M. Inorg. Chem. 1974, 13 (6),
1339-1342. (b) Khare, G. P.; Doedens, R. J. Inorg. Chem. 1976, 15 (1),
86-90. (c) Aime, S.; Gervasio, G.; Milone, L.; Rossetti, P. L.; Stanghellini,
J. Chem. Soc., Dalton Trans. 1978, 534-540.
(13) (a) Sadler, S. R.; Karo, W. Organic Functional Group Prepara-
tion: oximes; Academic Press: New York, 1972; Vol. 3, Chapter 11, pp
365-405. (b) Vogel, A. I. Textbook of Practical Organic Chemistry, 5th
ed.; Furniss, B. S., Hannaford, A. J., Smith, P. W. G., Tatchell, A. R., Eds;
Longman Scientific & Technical/Wiley: New York, 1989, pp 1332-1481.