Palladium on Barium Sulfate1


[7440-05-3]  · Pd  · Palladium on Barium Sulfate  · (MW 106.42)

(usually supported on BaSO4, or an appropriate form of carbon, when used to catalyze the hydrogenation of acyl chlorides to aldehydes, the Rosenmund reduction;2 useful catalyst for many other hydrogenations1b-e)

Alternate Name: Rosenmund catalyst.

Form Supplied in: Pd-on-BaSO4 and Pd-on-C are available commercially or may be prepared.3

Handling, Storage, and Precautions: the catalysts may be stored indefinitely in well-sealed containers.1e Although the unused catalysts can be exposed to a clean atmosphere, they may ignite organic solvent vapors; heating a Pd-on-C catalyst in a vacuum drying oven at 115 °C for more than 48 h causes it to become extremely pyrophoric.4 After use, all catalysts are liable to contain adsorbed hydrogen and may ignite when dried. The filtered catalyst should be kept wet and away from combustible vapors or solvents.

Traditional Rosenmund Procedures.

The palladium-catalyzed hydrogenation of an acid chloride to an aldehyde is known as the Rosenmund reduction (eq 1). In the original procedure, hydrogen 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 acyl chlorides, for others the further reduction of the aldehyde to the alcohol, and the consequential formation of esters, ethers, and hydrocarbons, seriously lowers the yield of the aldehyde.1 In initial experiments, it was reported that benzoyl chloride was converted almost completely to benzaldehyde; however, repetition of the same experiment, but with all reactants carefully purified, gave none.5 Seeking possible catalyst modifiers or regulators, it was found that quinoline-sulfur, a crude preparation of thioquinanthrene, was most suitable.5,6 Other regulators which have been recommended are pure thioquinanthrene, thiourea, and tetramethylthiourea.5,7 The purity of the solvent, which is used in much larger amounts than any of the reactants or the catalyst, is a key to reproducible reductions.8,9 Attaining the lowest temperature at which HCl is evolved was reported to optimize the yield of aldehyde.1a

In a 1948 review, it is claimed that For accomplishing this transformation, RCO2H -> RCHO, the Rosenmund reduction is probably the most useful method for application to a large number of aldehydes of varied types.1a This critical review describes the scope and limitations of the reaction, the experimental conditions, reagents, and procedures and includes tables recording the acid chlorides whose reduction by the Rosenmund method had been reported to November 1947.

Rosenmund described a simple apparatus for performing the reduction.5 A detailed description of a more elaborate apparatus and procedure used for the hydrogenolysis of b-naphthoyl chloride (0.30 mol) in xylene catalyzed by 5% Pd/BaSO4 and regulated by quinoline-sulfur was given by Hershberg and Cason (eq 2).10 They recommended that a poison always be added to ensure controlled conditions. The hydrogenolysis of mesitoyl chloride in xylene over unpoisoned Pd/BaSO4 is described in the same volume; vigorous stirring shortens the reaction time by about one third.11

The omission of catalyst poisons is common and the original Rosenmund procedure2 has been successful with acid halides containing other functional groups, or condensed benzenoid or heterocyclic systems.1a For example, discouraged by attempts to 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 quantitative yield.12 The reduction of the related compound with a methyl group proximate to the C(O)Cl group gave only a 49% yield of the aldehyde (eq 4) (however, see below).

A procedure for the unpoisoned 10% Palladium on Carbon catalyzed hydrogenation of a-phthalimido acid chlorides to the aldehydes in benzene at 40 °C has been described.13 To cause the benzene to reflux at 40 °C, the pressure is lowered with a vacuum pump which is attached to the outlet in a manner which allows the collection and titration of the evolved HCl. This procedure was suited particularly for the preparation of the phthaloyl methionine aldehyde (eq 5) but the (±)-phenylalanine and (±)-alanine derivatives gave yields of 93% and 94% respectively with benzene refluxing at 1 atm. An almost identical low temperature (reduced pressure) procedure was used to hydrogenate a diacid chloride to the dialdehyde in 92-94% yield (eq 6).14

Rosenmund Reductions within Closed Systems.

To avoid the higher temperature and the hazard of free flowing hydrogen of the classical Rosenmund procedure, particularly for large scale preparations, an autoclave can be used for the Pd/C catalyzed hydrogenolysis of 3,4,5-trimethoxybenzoyl chloride to the aldehyde (yield, 64-83%); the reduction was done at 35-40 °C and H2 (4 atm) in toluene containing quinoline-S with anhydrous sodium acetate as HCl adsorber (eq 7).4,15 The same reaction has been achieved repeatedly in 80-90% yields by the Rosenmund procedure without added regulators and either Pd/BaSO4 or Pd/C catalysts and either xylene or PhOMe as solvent.1a

Sakurai and Tanabe were the first to report the use of a closed system for the Pd/BaSO4 catalyzed hydrogenolysis of an acyl halide.16 The reduction (H2, 1 atm) was conducted at rt in the presence of a hydrogen chloride acceptor, N,N-dimethylaniline, and acetone as solvent. N-Phthaloyl derivatives of (±)-a-amino acid chlorides have been hydrogenated to the aldehydes using 10% Pd/C in the solvent ethyl acetate (H2, 3 atm) in the presence of dimethylaniline, with yields of over 90%.13

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 acceptor to obtain excellent yields of palmitaldehyde (96%) and decanaldehyde (96%).17 Peters and van Bekkum chose ethyldiisopropylamine as HCl acceptor due to the competitive reduction of N,N-dimethylaniline, which obscured the end-point (vol H2) of the hydrogenolysis of the acid chloride.18 The mild conditions converted the sterically hindered carbonyl chloride function in 1-t-butylcyclohexanecarbonyl chloride to the aldehyde (78%), although t-butylcyclohexane was the sole product of the original Rosenmund procedure (eq 8). Burgstahler and Weigel also modified the Sakurai and Tanabe procedure by using 2,6-dimethylpyridine in place of N,N-dimethylaniline and THF as solvent with either Pd/BaSO 4 or Pd/C as catalyst to obtain excellent yields of 15 sensitive aliphatic and alicyclic aldehydes such as hexanedial (74%) and (Z)-9-octadecenal (96%) (eq 9).19 The reaction temperature was lowered to 0 °C to convert dehydroabietic acid chloride to the aldehyde (92%) (eq 10).19

Both aliphatic and aromatic acid chlorides are reduced smoothly at room temperature and atmospheric pressure to aldehydes with 10% Pd/C as catalyst, acetone or ethyl acetate as solvent, and ethyldiisopropylamine as HCl acceptor.20 The reaction proceeds with high selectivity; over reduction is less than 1%, and nitro and chloro substituents in benzoyl chlorides are unaffected, as is the double bond in cinnamoyl chloride.

Recent Practice.

Some more recent examples show that both the older and the newer procedures are used successfully. As an important step in the preparation of 10-nor-cis-a-irone, the classical Rosenmund reduction (H2, 5% Pd/BaSO4, toluene/reflux) converted the acid chloride (1) to the product aldehyde in 93% yield (eq 11).21

The semialdehyde derivatives of aspartic and glutamic acids have been obtained in good yields and in higher purity than by hydride reductions; acid-sensitive protecting groups are unaffected.22 The acid chlorides (2) and (3) (benzyloxycarbonyl (Z) derivatives) were converted to the aldehydes using an unpoisoned catalyst (5% Pd/BaSO4, boiling toluene, H2) (eq 12). The same procedure was used to reduce the acid chloride (4), derived from L-alanine, to the aldehyde in 93% yield (eq 13).23

To protect the acid labile t-butoxycarbonyl protecting group in acid chloride (5), the Burgstahler procedure (H2, 5% Pd/C, 2,6-lutidine, THF, 10-15 °C) converted (5) to the aldehyde (eq 14).19,22

The quinoline-sulfur system was used to prepare methyl 4-oxobutanoate from 3-methoxycarbonyl chloride as the first of a three-step synthesis of a series of 5-vinyl g-lactones.10,24

Kinetics and Mechanism of the Rosenmund Reaction.

The kinetics of the amine-modified Rosenmund reduction has been examined in detail.20 In the absence of the tertiary amine, the hydrogenolysis of 4-t-butylbenzoyl chloride proceeds beyond the aldehyde stage to a complex mixture with bis(4-t-butylbenzyl) ether as the main product. In the presence of the efficient HCl acceptor zeolite NaA, most of the side reactions (acid catalyzed) are suppressed, but reduction proceeds to 4-t-butylbenzyl alcohol. In the presence of the tertiary amine, the aldehyde is the sole product. However, benzaldehydes subjected to the conditions of the amine-modified reduction are hydrogenated to the alcohols, but more slowly than in the absence of the amine and substantially slower on a catalyst which has been used previously in a hydrogenation of an acid chloride. The nature of the deactivation is a subject of speculation.20,25

The tertiary amine not only neutralizes HCl, but also acts as a nucleophile which serves to moderate the reaction and enhance the selectivity by competing with both the acid chloride and the product aldehyde for active sites on the catalyst. A useful analogy is the effect of tertiary amines upon increasing the selectivity of the hydrogenation of alkynes to alkenes on palladium catalysts.1b,26,27 The solvent also may compete for active sites; for example, the rate constants for the Pd-catalyzed hydrogenation of cyclohexene, corrected for the difference in the solubility of H2 in the solvents, are smaller in benzene and smaller still in xylene, both commonly used in the Rosenmund reduction, than in saturated hydrocarbons.28 The presence of nucleophilic groups elsewhere in the acid chloride may also act to moderate the reduction and affect selectivity in the absence of an added catalyst poison.

Aliphatic acid chlorides generally are more easily hydrogenolyzed than are aromatic ones; however, the Peters and van Bekkum paper contains the most direct comparison of relative reactivities for some representative carbonyl chlorides (15 compounds including 10 aromatic).20 For benzoyl chlorides, electron-donating substituents increase the reaction rate while electron-withdrawing substituents have a retarding effect. The rates of hydrogenation of aroyl chlorides generally are faster in the solvents ethyl acetate or THF than in acetone.

The mechanism of the Rosenmund reduction has been discussed in relation to the characteristic reactions of transition metal complexes.29 It has been proposed that the acid chloride adds oxidatively to the palladium metal, forming a complex which gives rise to the observed products which depend upon the reaction conditions, e.g. temperature, H2 pressure, and solvent. Some dissolution of the palladium when heated with an acid chloride at about 100 °C was observed. However, exposing single crystals of palladium to heptanoyl chloride in pentane and H2 at room temperature for 52 h did not change the (755) crystal surface which had catalyzed the formation of the aldehyde.25 A means of representing catalytic processes on such crystal surfaces by analogy with the reactions of transition metal complexes has been given for catalytic hydrogenation.26

Other Hydrogenations.1b-e

Pd/BaSO4 has also been used in the conversion of alkynes to cis-alkenes.30 In some cases, where results of the reduction of alkynes to cis-alkenes with Lindlar catalysts (see Palladium on Calcium Carbonate (Lead Poisoned)) are unsatisfactory, the use of Pd/BaSO4 as the catalyst has been effective (eqs 15 and 16).31

The reverse has also been observed.32 Interestingly, the saturation of the trisubstituted alkene in humulinic acid B has also been reported with this catalyst.33

Hydrogenolysis of various functional groups has also been reported with Pd/BaSO4. For example, the conversion of vinyl epoxides to homoallylic alcohols,34 a-bromo-b-mesyluridines to hydrocarbons (eq 17),35 N,N-dibenzylamino acids to N-benzylamino acids,36 and the enantioselective mono-dehydrohalogenation of a,a-dichlorobenzazepin-2-one37 have all been reported.

The maximum % ee observed for a-chlorobenzazepin-2-one was 50%, but surprisingly the method was not effective for other substrates, including a,a-dibromobenzazepin-2-one. Eq 17 also shows the C-O bond of a benzyl ether was not cleaved while the C-O bond of a mesylate and a C-Br bond were both hydrogenolyzed.

Regioselective opening of a 1,2-disubstituted epoxide was observed with this catalyst (eq 18).38 The benzylic ketone was not reduced or hydrogenolyzed under the reaction conditions.

Related Reagents.

Palladium on Carbon; Palladium-Graphite; Palladium on Poly(ethylenimine).

1. (a) Mosettig, E.; Mozingo, R. OR 1948, 4, 362. (b) Kieboom, A. P. G.; van Rantwijk, F. Hydrogenation and Hydrogenolysis in Synthetic Organic Chemistry; Delft University Press: Delft, 1977. (c) FF 1967, 1, 975; 1974, 4, 367-368; 1979, 7, 275-276. (d) Rylander, P. N. Catalytic Hydrogenation in Organic Syntheses; Academic: New York, 1979. (e) Rylander, P. N. Hydrogenation Methods; Academic: New York, 1985. (f) Davis, A. P. COS 1991, 8, 286.
2. Rosenmund, K. W. CB 1918, 51, 585.
3. Mozingo, R. OSC 1955, 3, 181.
4. Rachlin, A. I.; Gurien, H.; Wagner, D. P. OS 1971, 51, 8.
5. Rosenmund, K. W.; Zetzsche, F. CB 1921, 54, 425.
6. Rosenmund, K. W.; Zetzsche, F.; Heise, F. CB 1921, 54, 638.
7. Affrossman, S.; Thomson, S. J. JCS 1962, 2024.
8. Zetzsche, F.; Arnd, O. HCA 1926, 9, 173.
9. Zetzsche, F.; Enderlin, F.; Flutsch, C.; Menzi, E. HCA 1926, 9, 177.
10. Hershberg, E. B.; Cason, J. OSC 1955, 3, 627.
11. Barnes, R. P. OSC 1955, 3, 551.
12. Danishefsky, S.; Hirama, M.; Gombatz, K.; Harayama, T.; Berman, E.; Schuda, P. F. JACS 1979, 101, 7020.
13. Foye, W. O.; Lange, W. E. J. Am. Pharm. Assoc. 1956, 45, 742.
14. Johnson, W. S.; Martin, D. G.; Pappo, R.; Darling, S. D.; Clement, R. A. Proc. Chem. Soc. 1957, 58.
15. Wagner, D. P.; Gurien, H.; Rachlin, A. I. ANY 1970, 172, 186.
16. Sakurai, Y.; Tanabe, Y. J. Pharm. Soc. Jpn. 1944, 64, 25 (CA 1951, 45, 5613).
17. White, Jr., H. B.; Sulya, L. L.; Cain, C. E. J. Lipid Res. 1967, 8, 158.
18. Peters, J. A.; van Bekkum, H. RTC 1971, 90, 1323.
19. Burgstahler, A. W.; Weigel, L. O.; Shaefer, C. G. S 1976, 767.
20. Peters, J. A.; van Bekkum, H. RTC 1981, 100, 21.
21. Maurer, B.; Hauser, A.; Froidevaux, J-C. HCA 1989, 72, 1400.
22. Bold, G.; Steiner, H.; Moesch, L.; Walliser, B. HCA 1990, 73, 405.
23. Hoffmann, M. G.; Zeiss, H-J. TL 1992, 33, 2669.
24. Perlmutter, P.; McCarthy, T. D. AJC 1993, 46, 253.
25. Maier, W. F.; Chettle, S. J.; Rai, R. S.; Thomas, G. JACS 1986, 108, 2608.
26. Siegel, S. COS 1991, 8, 430.
27. Steenhoek, A.; Van Wijngaarden, B. H.; Pabon, H. J. J. RTC 1971, 90, 961.
28. Gonzo, E. E.; Boudart, M. J. Catal. 1978, 52, 462.
29. Tsuji, J.; Ohno, K. JACS 1968, 90, 94.
30. (a) Figeys, H. P.; Gelbcke, M. TL 1970, 5139. (b) Burgstahler, A. W.; Widiger, G. N. JOC 1973, 38, 3652. (c) Johnson, F.; Paul, K. G.; Favara, D. JOC 1982, 47, 4254.
31. (a) Burgstahler, A. W.; Widiger, G. N. JOC 1973, 38, 3652. (b) Scheffer, J. R.; Wostradowski, R. A. JOC 1972, 37, 4317.
32. Audier, L.; Dupont, G.; Dulov, R. BSF(2) 1957, 248.
33. Burton, J. S.; Elvidge, J. A.; Stevens, R. JCS 1964, 3816.
34. Gossinger, E.; Graf, W.; Imhof, R.; Wehrli, H. HCA 1971, 54, 2785.
35. Furukawa, Y.; Yoshioka, Y.; Imai, K.; Honjo, M. CPB 1970, 18, 554.
36. Haas, H. J. B 1961, 94, 2442.
37. Blaser, H.-U.; Boyer, S. K.; Pittelkow, U. TA 1991, 2, 721.
38. Augustyn, J. A. N.; Bezuidenhoudt, B. C. B.; Swanepoel, A.; Ferreira, D. T 1990, 46, 4429.

Samuel Siegel

University of Arkansas, Fayetteville, AR, USA

Anthony O. King & Ichiro Shinkai

Merck Research Laboratories, Rahway, NJ, USA

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