PALLADIUM ON BARIUM SULFATE 1
reagents, and procedures and includes tables recording the acid
Palladium on Barium Sulfate1
chlorides whose reduction by the Rosenmund method had been
reported to November 1947.
Pd/BaSO4
Rosenmund described a simple apparatus for performing the
reduction.5 A detailed description of a more elaborate appara-
[7440-05-3] Pd (MW 106.42)
tus and procedure used for the hydrogenolysis of ²-naphthoyl
InChI = 1/Pd chloride (0.30 mol) in xylene catalyzed by 5% Pd/BaSO4 and
InChIKey = KDLHZDBZIXYQEI-UHFFFAOYAH regulated by quinoline-sulfur was given by Hershberg and
Cason (eq 2).10 They recommended that a  poison always be
(usually supported on BaSO4, or an appropriate form of carbon,
added to ensure controlled conditions. The hydrogenolysis of
when used to catalyze the hydrogenation of acyl chlorides to alde-
mesitoyl chloride in xylene over unpoisoned Pd/BaSO4 is des-
hydes, the Rosenmund reduction;2 useful catalyst for many other
cribed in the same volume; vigorous stirring shortens the reaction
hydrogenations1b l)
time by about one third.11
Alternate Name: Rosenmund catalyst.
Form Supplied in: Pd-on-BaSO4 and Pd-on-C are available com-
mercially or may be prepared.3 COCl CHO
H2, 5% Pd/BaSO4
Handling, Storage, and Precautions: the catalysts may be stored (2)
quinoline-S, xylene, reflux
indefinitely in well-sealed containers.1e Although the unused
74 81%
catalysts can be exposed to a clean atmosphere, they may ignite
organic solvent vapors; heating a Pd-on-C catalyst in a vacuum
ć%
drying oven at 115 C for more than 48 h causes it to become
The omission of catalyst poisons is common and the origi-
extremely pyrophoric.4 After use, all catalysts are liable to con-
nal Rosenmund procedure2 has been successful with acid halides
tain adsorbed hydrogen and may ignite when dried. The filtered
containing other functional groups, or condensed benzenoid or
catalyst should be kept wet and away from combustible vapors
heterocyclic systems.1a For example, discouraged by attempts to
or solvents.
obtain high yields with a variety of metal hydride reducing
reagents, Danishefsky et al. found that the original Rosenmund
procedure converts the acid chloride (eq 3) in an essentially quan-
Traditional Rosenmund Procedures. The palladium-cata-
titative yield.12 The reduction of the related compound with a
lyzed hydrogenation of an acid chloride to an aldehyde is known
methyl group proximate to the C(O)Cl group gave only a 49%
as the Rosenmund reduction (eq 1). In the original procedure, hy-
yield of the aldehyde (eq 4) (however, see below).
drogen is bubbled through a heated suspension of the catalyst,
Pd/BaSO4, in a xylene or toluene solution of the acyl chloride.2
The HCl formed is absorbed in water and titrated to monitor the
reaction s progress. Although the procedure works well for many
O O
O O
acyl chlorides, for others the further reduction of the aldehyde
H2, Pd/BaSO4
O O
(3)
to the alcohol, and the consequential formation of esters, ethers,
H H H H
O toluene, reflux O
H H
and hydrocarbons, seriously lowers the yield of the aldehyde.1
95%
O Cl O H
In initial experiments, it was reported that benzoyl chloride was
converted almost completely to benzaldehyde; however, repe-
tition of the same experiment, but with all reactants carefully
purified, gave none.5 Seeking possible catalyst modifiers or reg-
ulators, it was found that quinoline-sulfur, a crude preparation of O O
O O
thioquinanthrene, was most suitable.5,6 Other regulators which H2, Pd/BaSO4
O O
(4)
have been recommended are pure thioquinanthrene, thiourea, and H H H
H
O toluene, reflux O
H H
49%
tetramethylthiourea.5,7 The purity of the solvent, which is used in
O Cl O H
much larger amounts than any of the reactants or the catalyst, is
a key to reproducible reductions.8,9 Attaining the lowest temper-
ature at which HCl is evolved was reported to optimize the yield
A procedure for the unpoisoned 10% Palladium on Carbon
of aldehyde.1a
catalyzed hydrogenation of Ä…-phthalimido acid chlorides to the
ć%
aldehydes in benzene at 40 C has been described.13 To cause the
O O ć%
Pd/BaSO4
benzene to reflux at 40 C, the pressure is lowered with a vacuum
+ H2 + HCl (1)
R R
toluene or xylene pump which is attached to the outlet in a manner which allows the
Cl H
collection and titration of the evolved HCl. This procedure was
suited particularly for the preparation of the phthaloyl methio-
In a 1948 review, it is claimed that  For accomplishing this nine aldehyde (eq 5) but the (Ä…)-phenylalanine and (Ä…)-alanine
transformation, RCO2H RCHO, the Rosenmund reduction is derivatives gave yields of 93% and 94% respectively with benzene
probably the most useful method for application to a large number refluxing at 1 atm. An almost identical low temperature (reduced
of aldehydes of varied types .1a This critical review describes the pressure) procedure was used to hydrogenate a diacid chloride to
scope and limitations of the reaction, the experimental conditions, the dialdehyde in 92 94% yield (eq 6).14
Avoid Skin Contact with All Reagents
2 PALLADIUM ON BARIUM SULFATE
O O ć%
reaction temperature was lowered to 0 C to convert dehydroabi-
H2, 10% Pd/C
Cl
benzene, reflux, 38 40 °C
etic acid chloride to the aldehyde (92%) (eq 10).19
N SMe
reduced pressure
90%
H2, 5% Pd/C
O
quinoline-S, toluene
O O
+ CO
H
reflux
t-Bu
(5)
N SMe
t-Bu
(8)
1 atm H2, 10% Pd/C
O
acetone, i-Pr2NEt
O
Cl
t-Bu
25 °C
O
78%
H
H2, 10% Pd/C
COCl CHO
benzene, reflux, 30 35 °C
H H H H
(6)
1 atm H2, 10% Pd/C
reduced pressure
O O O O(9)
92 94%
COCl CHO
THF, 2,6-lutidine, 25 °C
7 7 7 7
Cl Cl 96% H H
Rosenmund Reductions within Closed Systems. To avoid i-Pr i-Pr
the higher temperature and the hazard of free flowing hydrogen
1 atm H2, 10% Pd/C
2,6-lutidine
of the classical Rosenmund procedure, particularly for large scale
(10)
preparations, an autoclave can be used for the Pd/C catalyzed THF, 0 °C
93%
H H
hydrogenolysis of 3,4,5-trimethoxybenzoyl chloride to the alde-
Cl H
ć%
hyde (yield, 64 83%); the reduction was done at 35 40 C and H2
O O
(4 atm) in toluene containing quinoline-S with anhydrous sodium
acetate as HCl adsorber (eq 7).4,15 The same reaction has been
Both aliphatic and aromatic acid chlorides are reduced smoothly
achieved repeatedly in 80 90% yields by the Rosenmund pro-
at room temperature and atmospheric pressure to aldehydes with
cedure without added regulators and either Pd/BaSO4 or Pd/C
10% Pd/C as catalyst, acetone or ethyl acetate as solvent, and
catalysts and either xylene or PhOMe as solvent.1a
ethyldiisopropylamine as HCl acceptor.20 The reaction proceeds
with high selectivity; over reduction is less than 1%, and nitro and
MeO MeO
chloro substituents in benzoyl chlorides are unaffected, as is the
4 atm H2, 10% Pd/C
quinoline-S, toluene
double bond in cinnamoyl chloride.
(7)
MeO COCl MeO CHO
NaOAc, 35 40 °C
64 83%
Recent Practice. Some more recent examples show that both
MeO MeO
the older and the newer procedures are used successfully. As an
important step in the preparation of 10-nor-cis-Ä…-irone, the clas-
Sakurai and Tanabe were the first to report the use of a closed
sical Rosenmund reduction (H2, 5% Pd/BaSO4, toluene/reflux)
system for the Pd/BaSO4 catalyzed hydrogenolysis of an acyl
converted the acid chloride (1) to the product aldehyde in 93%
halide.16 The reduction (H2, 1 atm) was conducted at rt in the
yield (eq 11).21
presence of a hydrogen chloride acceptor, N,N-dimethylaniline,
and acetone as solvent. N-Phthaloyl derivatives of (Ä…)-Ä…-amino
H2, 5% Pd/BaSO4
COCl CHO
acid chlorides have been hydrogenated to the aldehydes using 10%
(11)
toluene, reflux
Pd/C in the solvent ethyl acetate (H2, 3 atm) in the presence of
93%
dimethylaniline, with yields of over 90%.13
(1)
The Sakurai and Tanabe procedure (5% Pd/BaSO4) gave
high yields of arachidaldehyde (72%) and stearaldehyde (96%);
for convenience, N,N-dimethylacetamide was used as the acid
The  semialdehyde derivatives of aspartic and glutamic acids
acceptor to obtain excellent yields of palmitaldehyde (96%) and
have been obtained in good yields and in higher purity than by
decanaldehyde (96%).17 Peters and van Bekkum chose ethyldi-
hydride reductions; acid-sensitive protecting groups are unaf-
isopropylamine as HCl acceptor due to the competitive reduc-
fected.22 The acid chlorides (2) and (3) (benzyloxycarbonyl (Z)
tion of N,N-dimethylaniline, which obscured the end-point (vol
derivatives) were converted to the aldehydes using an unpoisoned
H2) of the hydrogenolysis of the acid chloride.18 The mild
catalyst (5% Pd/BaSO4, boiling toluene, H2) (eq 12). The same
conditions converted the sterically hindered carbonyl chloride
procedure was used to reduce the acid chloride (4), derived from
function in 1-t-butylcyclohexanecarbonyl chloride to the alde-
L-alanine, to the aldehyde in 93% yield (eq 13).23
hyde (78%), although t-butylcyclohexane was the sole product
of the original Rosenmund procedure (eq 8). Burgstahler and
Cbz Cbz
H2, 5% Pd/BaSO4
N N
Weigel also modified the Sakurai and Tanabe procedure by using O O
(12)
O O
toluene, reflux
2,6-dimethylpyridine in place of N,N-dimethylaniline and THF as
( )n ( )n
Cl H
solvent with either Pd/BaSO4 or Pd/C as catalyst to obtain excel- O O
(2) n = 1 n = 1, 87%
lent yields of 15 sensitive aliphatic and alicyclic aldehydes such
(3) n = 2 n = 2, 82%
as hexanedial (74%) and (Z)-9-octadecenal (96%) (eq 9).19 The
A list of General Abbreviations appears on the front Endpapers
PALLADIUM ON BARIUM SULFATE 3
O O
withdrawing substituents have a retarding effect. The rates of
Cl H
H2, 5% Pd/BaSO4
hydrogenation of aroyl chlorides generally are faster in the
(13)
O O
O O
toluene, reflux
N N solvents ethyl acetate or THF than in acetone.
MeO2C MeO2C
The mechanism of the Rosenmund reduction has been dis-
(4)
cussed in relation to the characteristic reactions of transition metal
complexes.29 It has been proposed that the acid chloride adds
To protect the acid labile t-butoxycarbonyl protecting group oxidatively to the palladium metal, forming a complex which
in acid chloride (5), the Burgstahler procedure (H2, 5% Pd/C, gives rise to the observed products which depend upon the reac-
ć%
2,6-lutidine, THF, 10 15 C) converted (5) to the aldehyde tion conditions, e.g. temperature, H2 pressure, and solvent. Some
(eq 14).19,22 dissolution of the palladium when heated with an acid chloride at
ć%
about 100 C was observed. However, exposing single crystals of
palladium to heptanoyl chloride in pentane and H2 at room tem-
N(Boc)2 1 atm H2, 5% Pd/C
2,6-lutidine
perature for 52 h did not change the (755) crystal surface which
Cl
CO2-t-Bu
THF, 10 15 °C had catalyzed the formation of the aldehyde.25 A means of rep-
O 78%
resenting catalytic processes on such crystal surfaces by analogy
(5)
N(Boc)2 with the reactions of transition metal complexes has been given
H for catalytic hydrogenation.26
(14)
CO2-t-Bu
O
Other Hydrogenations.1b e Pd/BaSO4 has also been used in
the conversion of alkynes to cis-alkenes.30 In some cases, where
The quinoline-sulfur system was used to prepare methyl 4-
results of the reduction of alkynes to cis-alkenes with Lindlar cat-
oxobutanoate from 3-methoxycarbonyl chloride as the first of a
alysts (see Palladium on Calcium Carbonate (Lead Poisoned))
three-step synthesis of a series of 5-vinyl Å‚-lactones.10,24
are unsatisfactory, the use of Pd/BaSO4 as the catalyst has been
effective (eqs 15 and 16).31
Kinetics and Mechanism of the Rosenmund Reaction. The
OH
kinetics of the amine-modified Rosenmund reduction has been
Pd/BaSO4
quinoline
examined in detail.20 In the absence of the tertiary amine, the
(15)
hydrogenolysis of 4-t-butylbenzoyl chloride proceeds beyond the
EtOH, H2
OH HO
95%
aldehyde stage to a complex mixture with bis(4-t-butylbenzyl)
OH OH
OH
ether as the main product. In the presence of the efficient HCl
CO2Me
acceptor zeolite NaA, most of the side reactions (acid catalyzed)
Pd/BaSO4
quinoline
are suppressed, but reduction proceeds to 4-t-butylbenzyl alco-
CO2Me
(16)
hol. In the presence of the tertiary amine, the aldehyde is the sole
H2 CO2Me
83%
product. However, benzaldehydes subjected to the conditions of
CO2Me
the amine-modified reduction are hydrogenated to the alcohols,
but more slowly than in the absence of the amine and substan-
The reverse has also been observed.32 Interestingly, the satura-
tially slower on a catalyst which has been used previously in a
tion of the trisubstituted alkene in humulinic acid B has also been
hydrogenation of an acid chloride. The nature of the deactivation
reported with this catalyst.33
is a subject of speculation.20,25
Hydrogenolysis of various functional groups has also been
The tertiary amine not only neutralizes HCl, but also acts as a
reported with Pd/BaSO4. For example, the conversion of vinyl
nucleophile which serves to moderate the reaction and enhance
epoxides to homoallylic alcohols,34 Ä…-bromo-²-mesyluridines
the selectivity by competing with both the acid chloride and the
to hydrocarbons (eq 17),35 N,N-dibenzylamino acids to
product aldehyde for active sites on the catalyst. A useful anal-
N-benzylamino acids,36 and the enantioselective mono-
ogy is the effect of tertiary amines upon increasing the selectivity
dehydrohalogenation of Ä…,Ä…-dichlorobenzazepin-2-one37 have
of the hydrogenation of alkynes to alkenes on palladium
all been reported.
catalysts.1b,26,27 The solvent also may compete for active sites;
PhCH2O Pd/BaSO4 PhCH2O
for example, the rate constants for the Pd-catalyzed hydrogena-
R R
H2, NaOAc
O O
tion of cyclohexene, corrected for the difference in the solubility
(17)
36%
of H2 in the solvents, are smaller in benzene and smaller still in
xylene, both commonly used in the Rosenmund reduction, than
MsO Br
in saturated hydrocarbons.28 The presence of nucleophilic groups
elsewhere in the acid chloride may also act to moderate the re- The maximum % ee observed for Ä…-chlorobenzazepin-2-one
duction and affect selectivity in the absence of an added catalyst was 50%, but surprisingly the method was not effective for
poison. other substrates, including Ä…,Ä…-dibromobenzazepin-2-one. eq 17
Aliphatic acid chlorides generally are more easily hydrogen- also shows the C O bond of a benzyl ether was not cleaved
olyzed than are aromatic ones; however, the Peters and van while the C O bond of a mesylate and a C Br bond were both
Bekkum paper contains the most direct comparison of relative hydrogenolyzed.
reactivities for some representative carbonyl chlorides (15 com- Regioselective opening of a 1,2-disubstituted epoxide was ob-
pounds including 10 aromatic).20 For benzoyl chlorides, electron- served with this catalyst (eq 18).38 The benzylic ketone was not
donating substituents increase the reaction rate while electron- reduced or hydrogenolyzed under the reaction conditions.
Avoid Skin Contact with All Reagents
4 PALLADIUM ON BARIUM SULFATE
O O
19. Burgstahler, A. W.; Weigel, L. O.; Shaefer, C. G., Synthesis 1976, 767.
O OH
Pd/BaSO4
H2 20. Peters, J. A.; van Bekkum, H., Recl. Trav. Chim. Pays-Bas 1981, 100,
Ph Ph
(18)
21.
92%
MeO O OMe MeO O OMe
21. Maurer, B.; Hauser, A.; Froidevaux, J-C., Helv. Chim. Acta 1989, 72,
1400.
Related Reagents. Palladium on Carbon; Palladium Graph- 22. Bold, G.; Steiner, H.; Moesch, L.; Walliser, B., Helv. Chim. Acta 1990,
73, 405.
ite; Palladium on Poly(ethylenimine).
23. Hoffmann, M. G.; Zeiss, H-J., Tetrahedron Lett. 1992, 33, 2669.
24. Perlmutter, P.; McCarthy, T. D., Aust. J. Chem. 1993, 46, 253.
25. Maier, W. F.; Chettle, S. J.; Rai, R. S.; Thomas, G., J. Am. Chem. Soc.
1. (a) Mosettig, E.; Mozingo, R., Org. React. 1948, 4, 362. (b) Kieboom, A.
1986, 108, 2608.
P. G.; van Rantwijk, F. Hydrogenation and Hydrogenolysis in Synthetic
26. Siegel, S., Comprehensive Organic Synthesis 1991, 8, 430.
Organic Chemistry; Delft University Press: Delft, 1977. (c) Fieser &
27. Steenhoek, A.; Van Wijngaarden, B. H.; Pabon, H. J. J., Recl. Trav. Chim.
Fieser 1967, 1, 975; 1974, 4, 367; 1979, 7, 275. (d) Rylander, P. N.
Pays-Bas 1971, 90, 961.
Catalytic Hydrogenation in Organic Syntheses; Academic: New York,
28. Gonzo, E. E.; Boudart, M., J. Catal. 1978, 52, 462.
1979. (e) Rylander, P. N. Hydrogenation Methods; Academic: New York,
1985. (f) Davis, A. P., Comprehensive Organic Synthesis 1991, 8, 286.
29. Tsuji, J.; Ohno, K., J. Am. Chem. Soc. 1968, 90, 94.
2. Rosenmund, K. W., Chem. Ber. 1918, 51, 585.
30. (a) Figeys, H. P.; Gelbcke, M., Tetrahedron Lett. 1970, 5139.
(b) Burgstahler, A. W.; Widiger, G. N., J. Org. Chem. 1973, 38, 3652.
3. Mozingo, R., Org. Synth., Coll. Vol. 1955, 3, 181.
(c) Johnson, F.; Paul, K. G.; Favara, D., J. Org. Chem. 1982, 47, 4254.
4. Rachlin, A. I.; Gurien, H.; Wagner, D. P., Org. Synth. 1971, 51, 8.
31. (a) Burgstahler, A. W.; Widiger, G. N., J. Org. Chem. 1973, 38, 3652.
5. Rosenmund, K. W.; Zetzsche, F., Chem. Ber. 1921, 54, 425.
(b) Scheffer, J. R.; Wostradowski, R. A., J. Org. Chem. 1972, 37,
6. Rosenmund, K. W.; Zetzsche, F.; Heise, F., Chem. Ber. 1921, 54, 638.
4317.
7. Affrossman, S.; Thomson, S. J., J. Chem. Soc. 1962, 2024.
32. Audier, L.; Dupont, G.; Dulov, R., Bull. Soc. Chem. Fr., Part 2 1957,
8. Zetzsche, F.; Arnd, O., Helv. Chim. Acta 1926, 9, 173.
248.
9. Zetzsche, F.; Enderlin, F.; Flutsch, C.; Menzi, E., Helv. Chim. Acta 1926,
33. Burton, J. S.; Elvidge, J. A.; Stevens, R., J. Chem. Soc. 1964, 3816.
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34. Gossinger, E.; Graf, W.; Imhof, R.; Wehrli, H., Helv. Chim. Acta 1971,
10. Hershberg, E. B.; Cason, J., Org. Synth., Coll. Vol. 1955, 3, 627.
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11. Barnes, R. P., Org. Synth., Coll. Vol. 1955, 3, 551.
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12. Danishefsky, S.; Hirama, M.; Gombatz, K.; Harayama, T.; Berman, E.;
1970, 18, 554.
Schuda, P. F., J. Am. Chem. Soc. 1979, 101, 7020.
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2, 721.
R. A., Proc. Chem. Soc. 1957, 58.
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1323. Merck & Co., Inc., Rahway, NJ, USA
A list of General Abbreviations appears on the front Endpapers