Easy and partial hydrogenation of aromatic carbonyls to benzyl alcohols using Pd/C(en)-catalyst

Article abstract of DOI:10.1039/a807486k

Although 10% Pd/C catalyzed hydrogenolysis of aromatic ketones and aldehydes readily affords methylene compounds via intermediary benzyl alcohols, the employment of 10% Pd/C-ethylenediamine complex [Pd/C(en)] as a catalyst eased the formation of benzyl alcohols.

Full text of DOI:10.1039/a807486k

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Easy and partial hydrogenation of aromatic carbonyls to benzyl
alcohols using Pd/C(en)-catalyst
Hironao Sajiki, Kazuyuki Hattori and Kosaku Hirota*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-Higashi,
Gifu 502-8585, Japan
Received (in Cambridge) 29th September 1998, Accepted 9th November 1998
Although 10% Pd/C catalyzed hydrogenolysis of aromatic
ketones and aldehydes readily affords methylene com-
pounds via intermediary benzyl alcohols, the employment
of 10% Pd/C–ethylenediamine complex [Pd/C(en)] as a
catalyst eased the formation of benzyl alcohols.
Table 1 Pd/C(en)-catalyzed partial hydrogenation of aromatic ketones
and aldehyde to benzyl alcohols
a,b
Entry
Substrate
Product
Yield (%)
The preparation of alcohols through reduction of ketones and
aldehydes is among the most fundamental subjects in organic
synthetic chemistry. This significant transformation has been
1
91
1
mainly accomplished by stoichiometric metal hydride reagents.
In contrast to a large number of effective stoichiometric
2
3
93
99
reagents and some catalytic homogeneous hydrogenation cat-
2–4
alysts
available for carbonyl reduction, few heterogeneous
hydrogenation catalysts for reduction of aldehydes and ketones
1
to alcohols have been developed. Although the heterogeneous
hydrogenation of aliphatic carbonyls does not occur easily as
a rule, aromatic carbonyls hydrogenolyze to methylene com-
pounds smoothly via formation of the intermediate benzyl
4
97
5,6
alcohol (Scheme 1, 1→3). Therefore, it is extremely difficult to
5
6
98
89
7
90
Scheme 1 Reagents and conditions: i, 10% Pd/C(en), H2 (balloon),
MeOH, 24 h; ii, 10% Pd/C, H (balloon), MeOH, <24 h.
2
isolate the intermediate benzyl alcohol selectively when hydro-
genating aromatic carbonyl compounds using a palladium cata-
lyst. While Ram and Spicer reported a transfer hydrogenation
8
9
86
86
94
7
method for the partial reduction of aromatic carbonyls using
8
1
0% Pd/C and ammonium formate, the main reduction tends to
be accompanied by a reductive amination reaction with nucleo-
philic ammonia released from ammonium formate. Therefore,
the development of heterogeneous palladium catalysts with
excellent chemoselectivity between aromatic carbonyls and
intermediary benzyl alcohols is highly desirable because of a
1
0
5
a
series of practical benefits.
The reaction was carried out using 0.5 mmol of the substrate in
We have recently established that a Pd/C catalyst formed an
isolable complex with ethylenediamine (en) employed as a cata-
lytic poison and the complex catalyst [Pd/C(en)] selectively cata-
lyzed the hydrogenation of various functional groups (e.g. ole-
fin, nitro, benzyl ester, or azido) without the hydrogenolysis of
the O-benzyl protective group or the N-Cbz protective group of
MeOH (2 mL) with 10% Pd/C(en) (10% of the weight of the substrate)
under a hydrogen atmosphere (balloon) for 24 h and the structures of
1
all the new compounds were determined by their IR, MS, and H NMR
b
spectra and HRMS or elemental analyses. Upon the use of com-
mercial 5 or 10% Pd/C instead of 10% Pd/C(en), the hydrogenolysis of
the aromatic carbonyl compounds readily proceeded to give fully
hydrogenolyzed methylene products in excellent yields.
9
aliphatic amines. We are now in a position to disclose that the
Pd/C(en) catalyst is very efficient for the partial reduction of
aromatic carbonyl compounds (Scheme 1, 1→2).
First, the catalytic hydrogenation of 1-tetralone was carried
out smoothly using the 10% Pd/C(en) catalyst† (10% of the
weight of the substrate) in MeOH under a hydrogen atmosphere
ated tetralin (run 1 in Table 1). In addition, a competition
experiment using a 1:1 mixture of 1-tetralone and cyclohex-
anone as a substrate indicated that only 1-tetralone was reduced
to the corresponding 1-hydroxytetralin and the non-aromatic
ketone, cyclohexanone, was quantitatively recovered
unchanged. However, upon using a 10% Pd/C catalyst such a
(
balloon) for 24 h to provide partially reduced 1-hydroxytetralin
in 91% isolated yield without formation of the fully hydrogen-
J. Chem. Soc., Perkin Trans. 1, 1998, 4043–4044
4043

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selective hydrogenation failed and tetralin was readily formed in
2% yield. To investigate the synthetic utility of this new find-
ing, the selective hydrogenation of aromatic carbonyl groups to
hydroxy groups was conducted on a variety of substrates (Table
and the filtrate was concentrated in vacuo to give in most
cases an analytically pure product. If the product were not
9
analytically pure, the residue was purified by flash column
10
chromatography.
1
). The results show that the aromatic carbonyl compounds can
be readily converted to the corresponding benzyl alcohols in
excellent yields. In addition, the reactions of the mono-aromatic
carbonyl group (runs 1–5 and 10) were very clean, and no
chromatographic separation was required to obtain spectrally
pure products. Although the resulting products from di-
aromatic ketones (runs 6–9) were contaminated by a trace
quantity of over-reduction product, the less polar methylene
contaminant could be removed easily by simple flash column
Acknowledgements
This work was supported by the Research Foundation of Gifu
Pharmaceutical University, Japan.
Notes and references
†
10% Pd/C(en) catalyst was prepared from 10% Pd/C according to the
9
10
chromatography. The reaction conditions were compatible
with the hydrogenation of an olefin functionality (run 3). On
the other hand, the O-benzyl protective group of 4-
reported method for the preparation of 5% Pd/C(en) catalyst.
1
R. C. Larock, Comprehensive Organic Transformations, VCH, NY,
1989, p. 527.
(
benzyloxy)benzophenone, which possesses an electron with-
drawing benzoyl group at the p-position, did not survive under
these conditions (run 9).
2 For non-asymmetric hydrogenation, see: M. J. Burk, T. G. P. Harper,
J. R. Lee and C. Kalberg, Tetrahedron Lett., 1994, 35, 4963, and
references cited therein.
9
The chemoselectivity of the hydrogenation could be attribut-
able to the difference of the coordination affinity between
longer-conjugated aromatic carbonyls and benzyl alcohols to
ethylenediamine-coordinated palladium. In Pd/C(en) catalyst,
the original affinity of palladium for π-electrons should be
reasonably reduced by ethylenediamine.
3
For asymmetric hydrogenation using homogeneous catalysts, see,
R. Noyori and H. Takaya, Acc. Chem. Res., 1990, 23, 345; H. Takaya
and T. Ohta, J. Synth. Org. Chem., Jpn., 1993, 51, 1013; H. Doucet,
T. Ohkuma, K. Murata, T. Yokozawa, E. Katayama, A. F. England,
T. Ikariya and R. Noyori, Angew. Chem., Int. Ed., 1998, 37, 1703
and references cited therein.
In summary, we have developed an efficient chemoselective
hydrogenation of aromatic carbonyl groups to benzyl alcohols
using the heterogeneous and easily handled Pd/C(en) catalyst
under neutral conditions. The hydrogenolysis of the intermedi-
ate benzyl alcohols to methylene compounds could be mostly
overcome. The chemoselectivity observed for aromatic carbonyl
groups over intermediate benzyl alcohols and the general utility
of this methodology will make this simple technique an attract-
ive addition to the range of procedures already known for this
4 For reviews on asymmetric transfer hydrogenations using homo-
geneous catalysts, see, G. Zassinovich, G. Mestroni and S. Gladiali,
Chem. Rev., 1992, 92, 1051; R. Noyori and S. Hashiguchi, Acc.
Chem. Res., 1997, 30, 97.
For reviews on hydrogenation, see, M. Freifelder, Practical Catalytic
Hydrogenation Techniques and Applications, Wiley-Interscience, NY,
5
1
971, p. 398; P. N. Rylander, Catalytic Hydrogenation in Organic
Synthesis, Academic Press, NY, 1979, p. 271; P. N. Rylander, Hydro-
genation Methods, Academic Press, NY, 1985, p. 157; S. Siegel,
Comprehensive Organic Synthesis, eds. B. M. Trost and I. Fleming,
Pergamon Press, NY, 1991, vol. 8, p. 417; M. Hudlicky, Reductions
in Organic Chemistry, American Chemical Society, Washington,
DC, 1996.
1
general transformation.
Experimental
General procedure for the partial hydrogenation of aromatic
carbonyls
6
7
W. H. Hartung and R. Simonff, Org. React., 1953, 7, 263.
L. M. Werbel, E. F. Elslager and W. M. Pearlman, J. Org. Chem.,
1
964, 29, 967.
8
9
S. Ram and L. D. Spicer, Synth. Commun., 1992, 22, 2673.
H. Sajiki, K. Hattori and K. Hirota, J. Org. Chem., 1998, 63, 7990.
A mixture consisting of aromatic carbonyl compounds (1.0
mmol), 10% Pd/C(en) (10% of the weight of the substrate) and
methanol (2 ml) was stirred at room temperature under a
hydrogen atmosphere for 24 h. The reaction mixture was
filtered using a membrane filter (Advantec DISMIC-13CP)
1
0 W. C. Still, M. Kahn and A. Mitra, J. Org. Chem., 1978, 43, 2923.
Communication 8/07486K
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J. Chem. Soc., Perkin Trans. 1, 1998, 4043–4044