Catalytic hydrogenation of aromatic ketones in the presence of cyclodextrins

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MOLECULAR CATALYSIS ELSEVIER

Journal of MolecularCatalysis 91 (1994) L3WL318

Letter

Catalytic hydrogenation of aromatic ketones in the presence of cyclodextrins Eliana Rocchini, Roberto Spogliarich, Maw-o Graziani” Dipartimento di Scienze Chimiche, Universit6 di Trieste. Via L. Giorgieri 1. 34127, Trieste. Italy; far. (+ 39-40)6763903

(Received 30 November 1993; revised 4 March 1994; accepted 4 March 1994)

Abstract Selectivity in the hydrogenation of acetophenone and benzylideneacetone catalyzed by various supported metals is affected by inclusion of the substrate in cyclodextrins. Results show that in some cases clean reactions can be performed at ambient conditions in water, and saturation of the aromatic ring can be prevented or minimized. The system is very simple and shows great potentialities as far as reactions carried out in aqueous solution on organic compounds. Key words: Cyclodextrins; Hydrogenation; Selectivity

1. Introduction

Selective reduction of aromatic ketones by heterogeneous catalysis is often problematic because of concurrent ring hydrogenation and/or hydrogenolysis. Different metals and different conditions have been used depending on the function to be reduced. Palladium is generally the best catalyst for side-chain reduction to the alcohol or to the hydrocarbon; rhodium, ruthenium and platinum are suitable for ring saturation, rhodium giving the best yield of cyclohexyl alcohol [ l-31. However, clean reactions are rare and mixtures of products are often obtained, or else drastic reaction conditions have to be used, sometimes with the addition of cocatalysts. The idea of the present work is to affect the selectivity of the reaction by inclusion of the substrate molecule in cyclodextrins. Organic compounds are known to form 1:1 adducts with cyclodextrins, if they possess a suitable hydrophobic group that *Corresponding author. 0304-5102/94/$07.00 0 1994 Elsevier Science B.V. All rights reserved SSDIO304-5102 (94)00061-Y

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can fit in the cavity. This kind of interaction has been exploited in many different stoichiometric and catalytic reactions [ 4-81. Additional advantages of cyclodextrin inclusion are the increased solubility of the organic compound in water, as well as a chiral environment created by the optically active oligosaccharide around the substrate molecule. In this work we report results on the use of inclusion compounds with p-cyclodextrin ( pCD) and dimethyl- P-cyclodextrin (DM PCD) in the hydrogenation of aromatic ketones catalyzed by heterogeneous systems.

2. Results and discussion The most significant results obtained on acetophenone and benzylideneacetone (BDA) with various heterogeneous catalysts are collected in the tables. The experiments were performed in water at room temperature, in the presence of 1 atm hydrogen. The inclusion compounds with PCD form a suspension in water, whereas DM/3CD adducts are completely soluble even at high concentrations. Indeed, dimethylated PCD is known to be 10 times more water soluble than the unsubstituted cyclodextrin [ 91. Results obtained with Ir/A1203 are reported in Table 1. The conjugated ketone BDA is first reduced to the saturated ketone and then to the alcohol. Some ring reduction occurs as the alcohol is produced during the reaction. By using the CD adducts as substrates, no ring reduction takes place either for acetophenone or BDA (except run 5)) and the reaction rate decreases significantly (see Table 1). The same reaction carried out on acetophenone in THF is slower, and gives a higher yield of alcohol. Table 1 Hydrogenation’

of ketones with Ir/Al,O,

Run

Substrateb

Conv. (%)

1

PhCOCH3

100

2 3 4

PhCOCH,/3CD PhCOCH,-DMKD BDA

34 42 100

5

BDA-/3CD

87

6

BDA-DMKD

100

Products

Yield (9%)

PhCH( OH)CH9

68 32 34 42 91 9 69 14 2 2 20 80

Cd-WH(OH)CH, PhCH(OH)CH3 PhCH(OH)CH, PhCH&H$ZH( OH) CHs C&,,CH2CH,CH(OH)CH, PhCH2CH$XCH3 PhCH2CH,CH(OH)CHa C&I, ,CH,CH,COCH, C&,CH,CH,CH(OH)CH, PhCH2CH2COCH3 PhCH2CH,CH(OH)CH,

Conditions: reaction time 24 h; solvent HzO; sub/cat = 50; pH2 = 1 atm. See Experimental section. “BDA = PhCH = CHCOCH,; pCD = pcyclodextrin; DM pCD = dimethyl- @cyclodextrin. PhCOCH,-CD, BDA-CD = isolated cyclodextrin adducts.

E. Rocchini et al. /Journal of Molecular Catalysis 91 (1994) L3132318

Table 2 Hydrogenation’

of acetophenone

L315

with Rh/A1,09

Run

Substrate

Conv. (%)

Products

Yield (%)

1 2

PhCOCH3 PhCOCH,-DMj3CD

100 100

C6H,,CH(OH)CH3 C,H,,CH(OH)CH3 C,H, KOCH, &HI KHzCH3

100 12 20 8

“Conditions and notes, see Table 1

FWA1203 is a very active catalyst for total reduction of acetophenone to cyclohexylmethylcarbinol (see Table 2). Some ring reduction occurs also on the ketone itself, giving cyclohexylmethyl ketone. The presence of cyclodextrin does not affect the reaction rate (87% conversion after 5 h in both cases), nor does it inhibit the reduction of the phenyl group. Some hydrogenolysis is also observed with DMPCD, therefore a mixture of products is obtained in this case (Table 2, run 2). Also FWC gives high yields of cyclohexyl alcohol: 100% of cyclohexylmethylcarbinol is eventually produced from acetophenone after 48 h of reaction. Inclusion in DMPCD does not affect the reaction rate (80% conversion after 5 h), but a much slower ring reduction is observed (compare runs 1 and 3 in Table 3). A similar effect is shown for BDA, although in this case it is complicated by a decrease in activity. /3CD here seems to promote ring reduction (see runs 4-6, Table 3). The chemoselectivity of the reaction is therefore often changed by the presence of cyclodextrins, as can be seen from the results reported in the tables. The 400 Table 3 Hydrogenation”

of ketones with Pt/C

Run

Substrate

Conv. (%)

Products

Yield (46)

1

PhCOCHS

100

PhCH(OH)CH3

94

CdLCH(OH)CH~ PhCH(OH)CH,

100

Cd&,CH(OH)CH3 PhCH(OH)CH,

59 41 49 45 85 15 8 83 9 10 15 68 48 47 3 2

2

PhCOCH,-@ID

3

PhCOCH,-DM

4

BDA

100

5

BDA-@ZD

93

6

BDA-DM /3CD

100

/3CD

“Conditions and notes, see Table 1

Cd&,CH(OWCH~ PhCH,CH,COCH, PhCHJH$H(OH)CH, Cd, ,CH,CH,CH( OH)CH3 PhCH2CH2COCH3 PhCH$H,CH(OH)CH, C&,CH2CH2CH(OH)CH9 PhCH2CH2COCHp PhCH2CH2CH( OH)CH, C&H, ,CH2CH2COCH3 C&,,CH2CH2CH(OH)CH,

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MHz ‘H NMR spectrum of a 1:l mixture of acetophenone and 2,6-DMWD in DzO shows significant shifts of the signals of H3 and H5 of the CD, together with some shifts of the phenylic signals of the ketone. The hydrogen atoms at the 3 and 5 positions point towards the inside of the cavity, and a shift of their proton resonances is an indication of the formation of an adduct. This shows that the phenyl ring of acetophenone is inserted in the cavity of CD, as usually occurs in the case of aromatic molecules. It seems reasonable that the inclusion of the organic molecule into the cyclodextrin cavity through the phenyl ring inhibits the reduction of the latter, and the adduct approaches the metallic surface from the side of the carbonyl group, therefore giving the aromatic alcohol as a product. Of course, an equilibrium is always present in solution between the inclusion compound and free CD and substrate; the degree of dissociation, however, can be minimized by operating at high adduct concentrations, which is possible in the case of DMKD. As an alternative, the presence of an excess of CD is necessary to shift the dissociation equilibrium. In the case of Ir/A1203, CD inclusion allows the reaction to proceed more slowly, but cleanly on the carbonyl group, with 100% selectivity. Deactivation is observed with @CDfor longer reaction times, whereas very high yields of aromatic alcohols (up to 99%) are obtained by using DM/3CD adducts both of acetophenone and BDA. In this case the mechanism suggested above is apparently operative. The lower reaction rate is probably due to steric interactions between the surface and the adduct. Hydrogen bonding might also be involved between the hydroxy groups of the cyclodextrin and the support. If [ Ir( cod) CI] 2 is used as the catalyst precursor, a very active system is produced by reduction of COD and subsequent formation of a grey suspension of finely divided metallic iridium. 100% of cyclohexyl alcohols are obtained both from acetophenone and BDA in 24 h. The presence of CD in this case seems to slow down the reaction to some extent, but selectivity remains unaffected. Ring reduction is much slower if THF is used as solvent instead of water. In regard to the Rh and Pt catalysts, their high activity towards saturation of aromatic systems makes it difficult to prevent ring reduction. Rhodium is known to catalyze ring saturation and/or hydrogenolysis of aromatic ketones, depending on the experimental conditions [ l-3,10,1 11. Apparently, the hydrogenation in the case of Rh/A1203 and Pt/C proceeds at least in part on the free substrate in equilibrium with the CD adduct. Still, very high yields of phenylethanol can be obtained with Pt/C by using the PhCOCH,-DMPCD adduct and by stopping the reaction at the appropriate time, since the reduction of the carbonyl group and of the aromatic ring takes place in two successive steps. Ring reduction could be further minimized by operating in alkaline medium [ 21. Fomasier et al. reported that in the reduction of substituted pyridines in alkaline solution catalyzed by Pd/C, there is a very limited influence of PCD on the selectivity of the reaction; with some substrates, however, the rates of conversion to the alcohol and hydrocarbon are enhanced. The authors conclude that there are almost

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negligible interactions between the inclusion complexes and the catalyst [ 51. Our results, however, indicate that in our experimental conditions there is an interaction in some cases, depending on the choice of catalyst and substrate. Optical yields, when determined, were very low (2-3s e.e.). This could be explained either by the low asymmetry induced by cyclodextrins in general, and/ or by the fact that the adduct substrate-cyclodextrin is too flexible in these conditions. It appears that a high degree of crystallinity is generally required for these adducts to give good asymmetric inductions [ 8-121. However, low temperature and controlled crystallinity of the cyclodextrin adducts could lead to significant improvements. Generally speaking, these results show that the selectivity of the hydrogenation by heterogeneous systems can be affected by cyclodextrin inclusion, thereby making it possible to reduce some functions specifically or in high yields, while protecting other functions from saturation. By choosing the right solvent and conditions, selectivity and activity can be optimized. The hydrogenation system is very simple and one can operate at ambient conditions. The product can be easily recovered from the reaction mixture by filtration and/or extraction with organic solvent. DMPCD shows the highest potential as far as reactions carried out in aqueous solution, since the solubility of the substrate is greatly enhanced by inclusion and it is possible to operate at high concentrations, preventing at the same time dissociation of the adduct. This is particularly important when dealing with substrates with low association constants. Studies on the interaction between transition metal complexes and cyclodextrins are also currently being carrried out in our laboratory. This is a very promising field, and the subject has been recently reviewed [ 131. Some phase-transfer and homogeneous catalytic reactions have already been attempted by Alper [ 10,11,1416]. We feel that the synthesis and the use of such modified complexes could be of great interest in homogeneous catalysis, especially in aqueous solution and in asymmetric reactions. Our preliminary results are encouraging enough for us to carry on in this direction.

3. Experimental Acetophenone and BDA were purified before use by distillation and recrystallization, respectively. pCD (Fluka) and DM ED (Aldrich) were used as received. /ED adducts were prepared by adding the ketone to a saturated aqueous solution of /3CD. After several hours of stirring, the white solid which precipitated was filtered, washed with water and ether, and dried under vacuum. DMKD adducts were prepared by adding 1 equiv. of ketone to an aqueous solution of DMPCD. After stirring overnight, the water was evaporated and the white solid dried under vacuum.

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Ir/Al,O, (1.5% Ir) and Rh/A1203 (2.25% Rh) were prepared by the incipient wetness method from the chloride salts. After impregnation, the catalysts were dried at 12O”C,calcined at 400°C and reduced in Hz at 200°C for 2 h. Pt/C ( 10% Pt) was purchased from Fluka and used as received. [Ir(cod)Cllz was synthesized by a known method [ 171. Hydrogenation reactions were carried out in conventional glassware with magnetic stirring and 1 atm hydrogen. Procedure: 0.02 mmol of catalyst (referred to actual metal content) were suspended in 10 ml water under argon. The system was kept under hydrogen for 10 min, and the substrate (or its CD adduct) was then added. Samples were taken by syringe, extracted with ether, and analyzed by GLC using a Perkin-Elmer Sigma 3B gas chromatograph equipped with a HWD detector and a Supelcowax 10 wide-bore capillary column. Optical yields were determined by optical rotation measurements. using a Perkin Elmer 141 polarimeter. NMR spectra were run on a JEOL EX 400 spectrometer.

Acknowledgements

Authors thank CNR, Progetto Finalizzato Chimica Fine II for financial support and for a postdoctoral grant to E.R. Authors are also grateful to Drs. C. de Leitenburg and P. Fomasiero for preparing the rhodium and iridium catalysts.

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