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polyethylenimine catalysts
1
PALLADIUM/POLYETHYLENIMINE
CATALYSTS
G. P. ROYER*, WEN-SHIUNG CHOW and KIMI S. HATTON Department of Biochemistry, OH 43210 (U.S.A.) fReceived May 16,1984;
Ohio State University,
484 W. 12th Avenue, Columbus,
accepted October 5,19&Z)
Summary We report the preparation and evaluation of palladium catalysts made from polyethylenimine (PEI)/silica composites. PEI was adsorbed to either porous silica beads or silica gel, Following crosslinking, the material was leached with bass to increase the surface area and availability af the polymer. The PEI/siiicas rapidly chelate Pd2+ from solution. Reduction of the chelated metal ions can be accomplished with sodium borohydride. Pd/PEI/silica beads are used effectively in suspension with formic acid as the hydrogen donor; deprote~tion of Cbz-Glyeine-O-t-butyf (where Cbz-carbobenzoxy) is very rapid with this catalyst compared to p~adium on carbon. The Pdf PEI/silica gel catalyst can be used effectively with hydrogen gas for the reduction of nitrobenzene in methanol. Both catalysts are conveniently separated from product by simply decanting the supernatant solution. The catalysts (1% Pd) have shown no pyrophoric behavior and they are reusable. Hydrophobic derivatives of the catalysts were prepared with the hope that apolar reactants would be attracted to the metal sites with a concomitant enhancement of rate. The introduction of apolar groups into the catalyst matrix did not, however, result in a more effective catalyst compared to the catalyst made from the unmodified material.
Introduction Polyethylenimine (PEI) is a branched polymer obtained by the polymerization of aziridine: -
t CHD-I,NK
),
*Author to whom eorresporidence should be addressed at: Amoco Research Center, P.O. Box 400, Naperville, IL 60566, U.S.A. 0304~S102/85/$3,30
@ Elsevier Sequoia/Printed
in The Netherlands
The branching
may be represented
as follows:
The amine distribution is 25% primary, 50% secondary and 25% tertiary [ 11. We have described the immobilization of PEI on porous silica beads [ 2 ] and silica gel [3]. A three-step process is used to produce materials which we have termed ‘polymer ghosts’ (Fig, 1): first, PEI is adsorbed onto the inorganic particles; the adsorbed polymer layer is then chemically crosslinked; the composite is then leached to remove all or part of the inorganic material to provide a material with high surface area [ 4 1. Palladium catalysts can be prepared as shown in Fig. 2. The Pd2+ binds strongly to the amine support, and metal loadings of up to 5% can be achieved. The reduction of the palladium may be accomplished with sodium borohydride in water or organic solvent; aqueous formaldehyde is also effective. Palladium/PEI/silica beads and palladium/PEI/silica powder have been prepared with porous silica beads (surface area 52 m2 g-‘) and silica gel (500 m2 g-i) as the respective starting materials. Both catalysts are active with hydrogen or formic acid. In this paper, we describe their use in debenzylation reactions and in the reduction of aromatic nitro compounds. The catalysts are reusable, and readily settle out from suspension. Catalysts (1% Pd) have shown no pyrophoric behavior when used with organic solvents.
@ inorganic core
I
0
f--A \/
PEUSilica
bead
0
0 Pd/PEI/Silica catalyst
bead
Fig. 1. Preparation of PEIfsiiica beads. Fig. 2. Schematic diagram showing metal chelation and reduction to form Pd/P~I~sili~ bead catalyst.
3
PEI-‘ghosts’ attracted us because of their high surface area and metal chelating capacity. In addition, because the amino groups of the catalyst support are readily modifiable with straightforward chemistry, we felt that the system provided an opportunity to alter the environment of the metal. Since large rate enhancements have been observed as a result of the hydrophobic effect, one goal of this work was to prepare and evaluate hydrophobic catalysts. In theory, the rate of reaction involving such catalysts could be changed according to the hydrophobic character of the solvent. Solvent compositions which were just hydrophobic enough to dissolve the reactant would be desirable in this case; the reactant would tend to leave the solvent and bind to the catalyst support in the vicinity of the metal. Also, negatively-charged reactants would be attracted to the catalyst and positively-charged products repelled, in analogy to some enzyme reactions. Experimental
section
Materials PEI was purchased from Cordova Chemical Company as Corcat@ (MW 60 000, 33% PEI in water). Xama@-2, a polyfunctional aziridine crosslinking agent, was also obtained from Cordova. Silica gel (Grade 923) was from Davison/W.R. Grace, and silica beads were supplied by Corning (Code Number 691952,35-40 mesh, average pore diameter 275 A). PEI adsorption to silica beads The PEI binding capacity of silica beads was determined in the following manner. A sample of silica (0.1 g) was placed into a 12 ml screw-cap tube with methanol (about 7 ml). The tubes were placed in a heated desiccator and a vacuum was applied for removal of trapped air. The methanol was removed with a pipet fitted with nylon net. Five ml of the desired PEI solution were then added, and the tube was tightly capped. The PEI/silica suspensions were rotated end-over-end for 3 h and the supematant solution was removed. In the experiments which lead to the results shown in Fig. 3, 8.07.06.05.0 4.0 -
IPEII in MeOH (mg/ml)
Fig. 3. The binding of PEI to silica beads. One g of silica’beads was equilibrated with methanolic solutions of PEI. The beads were then washed twice with methanol, dried, and then ground to a fine powder. The PEI content was determined by use of ninhydrin reagent [5] 0.
4
the beads were washed once with methanol prior to the determination of primary amine content. In this manner, loosely bound PEI would be removed. Methanol (5 ml) was added, and the mixture was agitated by vortex mixer for 5 s, The wash was removed, and the beads were dried in a heated desiccator and then ground to a fine powder for the determination of primary amine content by the ninhydrin test [ 51. Preparation of PEIhilica beads PEI/silica beads were synthesized using a rotary evaporator (Buchi, RE120). Fifty grams of silica beads were placed in a 1000 ml round-bottom flask, and 200 ml of PEI/meth~ol were added. Trapped air was removed by lowering the pressure while the flask was rotated at maximum speed at room temperature. Methanol was then evaporated (35 “C). The resulting PEI beads were dried in a heated vacuum desiccator. Twenty g of PEI/silica beads (4 wt.%), were placed in a 250 ml round-bottom flask, and 50 ml of 0.5% glut~~dehyde in THF were added. The flask was placed on the rotary evaporator and rotated at l/4 maximal speed for an additional 30 min. The THF solution was removed by suction with a gas dispersion tube and replaced with 100 ml of aqueous NaBH4 (1%). The flask was rotated at l/4 maximal speed for 1 h. The borohydride solution was decanted and 100 ml of aqueous formic acid (15%) was added. After rotation for 1 h at l/4 maximal speed, the formic acid solution was decanted and 5 N NaOH (200 ml) was added. After leaching the preparation for 1 h at l/4 maximum rotation speed, the beads were washed to neutrality with water and dried in a vacuum desiccator. All of the above operations were performed at room temperature. Ad~rption of palladium The binding of palladium by the PEI composites can be followed spectrophotometrically (375 nm). A palladium acetate stock solution was prepared by dissolving PdCl* (0.2 g) in 2 ml of concentrated HCl with heating. Addition of sodium acetate solution (48 ml, 15% w/v NaAc- 3Hz0) yields the stock solution which contains 2.5 mg of palladium per ml. To determine the adsorption rate, 1 g of PEI/silica composite was shaken on a wrist-action shaker with 4 ml of palladium acetate stock solution in a 25 ml Erlenmeyer flask. Samples were withdrawn at timed intervals for spectrophotometric analysis. The control experiment shown in Fig. 4 was performed with silica beads which were subjected to the procedure for preparing PEIfsilica beads from which the PEI was omitted. Sodium borohydride reduction in various solvents Water and several organic solvents were used in the reduction step of catalyst preparation. The concentrations of NaBHe in the solvents were as follows: 0.05 g ml-’ DMF, 0.025 g ml-’ diglyme, 0.02 g ml-’ ethanol and 0.25 g ml-’ water. These solutions were made by cooling the solvents below 5 “C in an ice-water bath and adding the specified amount of NaBH+
5
Several 1 g samples of support were placed in 25 ml Erlenmeyer flasks. After the PdZ+ was adsorbed from the PdCl*-NaAc solution, the supernatant was removed by suction through a pipet fitted with polyester net. The Pd2+ PEI/silica beads were washed two times (10 ml each time) with the solvent chosen for the reduction, and then 1 ml of the solvent was added to the beads. The flask was cooled to below 5 “C. The solutions of NaBHe in the chosen solvent were maintained at the same temperature. Reduction of the Pd2+ was carried out by pipetting an appropriate volume (50 mg NaBH4 g-i support) of the cold borohydride solution into the flask followed by a vigorous swirling motion. Reduction was allowed to continue for 15 min with agitation of the flask about every 5 min. Procedure for the reduction of Pd2’/silica beads in water using NaBH4 After the Pd2+ was adsorbed on the support, the liquid phase was removed from the solid beads (1 g) by suction through a pipet fitted with polyester net. The beads were washed with water two times (15 ml each). One ml of water was then added and the suspension was cooled in an icewater bath to between 0 and 2 “C. A solution of NaBHe in water was made by dissolving sodium borohydride in water (precooled to 0 - 4 “C). For the reduction of 1 g of support, NaBH4 (150 mg) was dissolved in 3 ml of cold water. One ml of this solution was added to the Pd?+/silica beads in water, and the beads were swirled rapidly for about 1 min. The beads were then allowed to sit in an ice-water bath for 0.5 h with intermittent swirling. At the end of this time, the supernatant was removed. The blackened beads were then washed twice with 10 - 15 ml of water. One ml of water was added and the flask was cooled in an ice-water bath. Reduction was repeated by adding 1 .O ml of the borohydride solution followed by a vigorous swirling motion. The bea.ds were allowed to sit in an ice-water bath for 30 min with intermittent agitation, washed four times with water (15 ml each time), and then washed two times with methanol (10 - 15 ml each time) prior to drying in a vacuum desiccator. Reduction in this fashion requires 100 mg NaBHe g-’ of beads. Preparation of octanoyl/PEI/silica beads Three g of PEI/glutaraldehyde/silica beads were placed in a 100 ml round-bottom flask, and 25 ml of 20 vol.% triethylamine in DMF were added. A vacuum was applied for 30 min for the removal of trapped air. The triethylamine solution was removed by decantation and 0.28 g of octanoyl chloride in 10 ml of DMF were added. An additional 1 ml of 20% triethylamine in DMF was added. The suspension was rotated at l/4 maximal speed on the rotary evaporator for 48 h at room temperature. The modified support was washed with 20% TEA in DMF, DMF, methanol, water and methanol and dried in a heated vacuum desiccator. Synthesis of octyl/PEI/silica beads Two g of PEI silica beads were placed in a 100 ml round-bottom flask and triethylamine/HMPA (20%, 25 ml) was added. A vacuum was applied
6
for the removal of trapped air as the flask was slowly rotated on the rotary evaporator. The supernatant solution was removed by suction with a gas dispersion tube, and the procedure was repeated. After removing the second wash, 10 ml of HMPA was added. To this suspension was added 1.23 g of octyl bromide and 1.29 g of tri~thylamine. The mixture was rotated at l/4 maximal speed on the rotory evaporator for 72 h at 50 “C. The HMPA solution was removed by suction through a gas dispersion tube, and the modified beads were washed with additional 20% triethylamine/HMPA, HMPA, and methanol and dried in a heated vacuum desiccator. Preparation 0 f PEI~sili~agel Silica gel (10 g) was mixed with the PEI stock solution (0.5 g PEI/lO ml MeOH). The methanol was removed with a rotary evaporator. The silica was then washed briefly with cold methanol to remove extraneous PEI and dried in a vacuum desiccator. Twenty-five ml of 1% (wt/v) glutaraldehyde in water was added to the silica gel and the suspension rotated at room temperature for 30 min. The glutaraldehyde solution was replaced with 25 ml of 1% PEI in methanol and rotated for an additional 30 min. The PEI solution was poured off, and NaBH4 (300 mg in 25 ml MeOH) was added. After rotation for 30 min, the preparation was washed with water, methanol and dried in a vacuum desiccator. Preparation of Pd/PEI/silica gel A palladium stock solution was made by mixing 1 ml of 1 N HCl with 85 mg PdC12 and heating to dissolve the mixture. Ten ml of a 15% solution of NaAc* 3Hz0 was added. This palladium stock solution (4.4 ml) was added to 2 g of PEIfsilica gel. Uptake of Pd2+ was complete within 10 min. The preparation was then reduced with 300 mg of NaBH, in 10 ml of cold MeOH. After washing with water, 10% formic acid/water and methanol, the catalyst was dried in a heated vacuum desiccator. Preparation of PEI/Xama@/silica gel PEI (10 g, 33% aqueous) was mixed with 0.3 g of Xama@-2 in 10 ml of MeOH and refluxed for 10 min. The volume was then adjusted to 50 ml with MeOH. Five ml of the PEI-Xama@ solution were mixed with 10 g of silica gel suspended in 100 ml of methanol. The mixture was stirred with an overhead stirrer and heated on a boiling water bath for 15 min. Methanol was then evaporated, and the PEI-silica was repeatedly suspended in water until the decanted wash water gave a negative ninhydrin test. The support was dried in a heated vacuum desiccator. Preparation of hydrophobic PEI/Xama@ silica gel supports (1) Acylation: PEI/Xama@ silica gel (5 g) was washed twice with 2% triethylamine in DMF (50 ml). Enough DMF was added to cover the support. To this suspension was added ~-nitrophenyl caproate (0.9 g) and triethylamine (0.13 ml). The reaction mixture was continuously rotated for
24 h at 5 “C. At the end of this time, the silica gel was filtered, washed with methanol and dried in a vacuum desiccator. (2) Reductive alkylation: (a) Aqueous buffer-methanol mixture. PEI/ Xama@/silica gel was mixed with hexanal (50 ~1) in a mixture of 0.1 M borate buffer (25 ml, pH 8.5) and methanol at 4 “C. NaBHa (70 mg total) was added in six equal portions over a period of 1 h with occasional agitation. The support was then washed with water and methanol, and then dried in a heated vacuum desiccator. The decrease in primary amine content was 14%. (b) In methanol. PEI/Xama*/silica gel (2 g) was washed with 2% trie~ylamine in DMF (50 ml) and suspended in 10 ml of meth~ol. To this suspension was added hexanal (340 ~1) in 2 ml of ethanol. The suspension was agitated occasionally. After 30 min, NaBHe (25 mg) was added in five equal portions over a period of 1 h. The support was then washed with water and methanol, and dried in a vacuum desiccator. The decrease in primary amine content was 32.5%. (3) Alkylution: PEI/X~a~ silica gel was suspended in 10 ml of DMF containing 100 ~1 of triethylamine. To this suspension was added 100 ~1 of benzyl bromide, and the mixture was rotated for 1 h at 90 “C. The material was washed with methanol and dried in a vacuum desiccator. The decrease in primary amine content was 28%. ~epa~tion of hyd~phobi~~PEI~~ilica bead and silica gel~palladium catalysts Hydrophobic/PEI/silica catalysts were synthesized by the same general method as underivatized PEI/silica catalysts. The only change in the procedure was the amount of time the hydrophobic derivatives were exposed to solutions of Pd*+. The underivatized PEI/silica beads and silica gel decolorized solutions of Pd*’ within 5 - 10 min, while the hydrophobic derivatives required 24 - 48 h. Since the hydrophobic PEI/silicas tend to float in aqueous solution, the suspension was rotated to ensure maximum exposure of the PEI/silica to the Pd*+ solution. After the supernatant solution of the Pd2+ became colorless, the preparation was reduced with sodium borohydride as previously described. Repeated use of palladium/PEI/~ilica catalysts in formic acid A sample of catalyst (0.2 g) was placed in a 25 ml Erlenmeyer flask and was assayed for activity using Cbz-Gly-O-t-butyl as the substrate in HCOOH:EtOH:H,O (assay described below). After about 60 - 70 min, the assay mixture was removed with a pipet fitted with polyester net. The catalyst was washed 4 times with 15 ml of methanol and dried in a vacuum desiccator. The Cbz-Gly-C-t-butyl assay was performed with this 0.2 g sample 10 times and the ti,* was determined for each run. Cbz--GTy+3-t-butyl assay A stock solution of Cbz-Gly-U-t-butyl stored at 4 “C. A 1:5 HCOOH:H,O solution
in ethanol was made and was prepared fresh daily. The
assay mixture consisted of 3.5 ml of HCOOH:EtOH:H,O and 0.12 g of CbzGly-O-t-butyl (2 ml of the HCOOH:HzO solution and 1.5 ml of the substrate in EtOH solution). The assay mixtures were agitated on a wristaction shaker at maximum speed. The shaking motion of the flask can be described as a 20” detection from the horizontal with approx~ately 240 excursions per minute. The distance travelled perpendicular to the horizontal was 2.5 cm. A weighed sample of catalyst was placed in a 25 ml Erlenmeyer flask and secured on the wrist-action shaker, The assay mixture was delivered to the flask (t = 0), the flask was stoppered with a perforated cork, and the speed of shaking was brought to the m~imum. Samples (4 ~1) were taken at timed intervals, and the extent of reaction was determined by ninhydrin analysis. Hydrogenation of nitrobenzene/re-use of the Pd/PEUsilica gel Nitrobenzene (10.3 ml, 0.1 mol), methanol (90 ml), and 2.1 g of 1% Pd/PEI/glu~~dehyde/sili~a gel were added to a 500 ml 3-neck roundbottom flask equipped with an overhead stirrer. Hydrogenation was performed at atmospheric pressure. The flow of hydrogen gas was fixed at a constant rate with a Gilmont flowmeter (0.5 1 min-‘, calibrated by air). The reaction was begun at room temperature. With no external temperature control the reaction mixture warmed to a temperature of about 56 “C. At timed intervals, aliquots (10 ~1) were removed and diluted with 5 ml of methanol and 95 ml of water. The samples were analyzed spectrophotometrically (220 - 320 nm). The stability test (reuse of 1% Pd/PEI/silica gel) was performed by using the same sample of catalyst 10 times, At the end of the reaction, the catalyst was filtered, washed with methanol, dried and recycled.
Results Pd/PEI/silica beads Preparation In order to arrive at optimal conditions for the PEI adsorption step, we studied the binding of PEI as a function of polymer concentration (Fig. 3). In this study, silica beads were equilibrated with methanolic solutions of PEI. Weakly-bound PEI was removed with a methanol wash prior to the determination of bound polymer. The saturation point is about 4 wt.% PEI/ silica. Crosslink~g is best done in a solvent that does not dissolve PEI; THF works well for this purpose. Glutaraldehyde and XamaQ (a multi-functional aziridine) are effective crosslinking agents. Uptake of Pd 2+ by PEI/silica beads is quite rapid (Fig. 4). PEI/silica (1 g) can adsorb 10 mg of palladium in less than 10 min. Adsorption of Pd2+ onto control beads (no PEI content) is not significant. Thus, binding of Pd2+ to the composite occurs exclusively through infraction with the amine ligand .
9
0 0
Control 0ctsnoyl
A
octyi
O.l-
h-_-s 5
10
^
c
=
0
15
20
25
30
5
Time (minuted
15
30
45
50
75
Time (minutes)
Fig. 4. Uptake of Pd 2+ by PEI/silica beads (0) and control silica beads containing no PEI (0). Fig. 5. Comparison of hydrophobic Pd/PEI/silica bead catalysts and unmodified Pd/PEI/ silica bead catalysts. The activity of the catalyst was measured using the removal of’the Cbz-group from Cbz-Gly-0-t-Bu in HCOOH:EtOH:water as described in the text. The assays were performed at 23 “C. Pd/PEI/silica beads 0; Pd/octanoyl PEI/silica beads 0; and Pdloctyl PEI/silica beads A.
TABLE 1 The primary amine content of hydrophobic PEI/silica sample
PEI/silica bead
PEI/silica beads
Group incorporated
-
Primary amine content (meq g+)
Modification of primary amine
0.22 - 0.30
-
(%)
0 octanoyl PEI/silica bead
CH3-(CH2&-
0.145
46
octyl PEI/silica bead
CHs-(CH2)s-CH2-
0.187
15
lauryl PEI/silica bead
CHs-(CH,),o--CH,-
0.194
35
Borohydride reduction of the Pd2+/PEI/silica beads can be done in a number of organic solvents. Double reduction with aqueous borohydride (5 g NaBH,/lOO g of beads) produces an acceptable catalyst.
10
Hydrophobic substitution of the PEI/silica beads was done in order to augment interaction of apolar reactants with the catalyst support (Table 1). Reaction rates with the hydrophobic catalysts were not as fast as those for unsubstituted catalyst beads {Fig. 5). Properties Pd/PEI/silica beads made by the procedure reported here have a surface area of 47 - 52 m2 g-’ (BET) (Table 2). The palladium content is 1.09% in good agreement with the theoretical value. The beads can be used in a packed bed reactor. Suspension of the beads by shaking is also effective. The beads settle quickly from suspension, which permits direct decantation of the. product. solution. Use of a magnetic stirrer results in rapid destruction of the beads. Pd/PEI/silica beads effectively catalyze the removal of the Cbz group’vvith formic acid as the hydrogen donor:
Pd/PEIjSiOz + HCOIH
*HNy’x
+ toluene
+ COZ
0 The Pd/PEI catalyst beads are more effective than palladium-on-carbon (1% Pd) with formic acid as the hydrogen donor (Fig. 6). With hydrogen gas using Cbz-Asp-Phe-OME, palladium-on-carbon is slightly more effective than the p~ladium beads (data not shown). Repeated use of the Pd/PEIf silica bead catalyst using formic acid as the hydrogen donor results in some loss of activity (Fig. 7). The catalyst may be partially reactivated by treatment with NaBH,. Pd~PEI~sili~ugel. ~epar~~io~ The PEI/silica gel is synthesized by adsorbing PEI to the extent of 5% onto silica gel and then washing with cold methanol. After drying the coated gel, crosslinking ii5 accomplished by treatment with aqueous glutaraldehyde. TABLE 2 Properties of Pd/PEI/silica catalysts Sample
BET surface area (m2 g-l 1
Cumulative pore volume (cm3 g-l)
Average pore radius (h
silica beads silica gel
47 499
0.70 0.30
265 14
11
!a 40 30 20 10 ~
”
10
20
30
40
12
606070
I
I
I
I
I
I
I
1
3
4
5
6
7
8
9
VI
Number of uses
Time (minutes)
Fig. 6. Comparison of 1% Pd-on-carbon and 1% Pd/PEI/silica beads in the removal of the Cbz group from Cbz-Gly-G-t-Bu in formic acid. Pd/PEIlsiliea beads 0; Pd/C Q Fig, 7. Reuse of the PdfPG/silica bead catalyst in formic acid/debloeking G-t-butyl.
of Cbz-Gly-
Using organic solvents in the crosslinking step tends to cause agglomeration of the gel particles. Uptake of Pd2+ by the PEI/silica gel is rapid and comp~able to the rate of uptake by PEI/silica beads. Adsorption is complete within 5 - 10 min; the extent of palladium uptake is greater than 95%. Reduction with borohydride can be accomplished with solvents such as methanol, ethanol and water. Hydrophobic derivatives of PEI/silica gel were made for two reasons for evaluation of the effects on the palladium catalyst activity and for chromato~aphic applications. The degree of hydrophobic substitution of the PEI/silica gel is shown in Table 3. Reaction rates with hydrophobic PEI/ silica gel catalysts were not as fast as those for the corresponding unsubstituted Pd/PEI/silica gel catalysts (Fig. 8). TABLE 3 Primary amine content of hydrophobic PEI/silica gels PEI/silica sample
Group incorporated
PEl/siliea gel
0
Primary amine content (meq 9’1
Modification of primary amine (%l
0.16
-
hexanoyl PEI/silica gel
CH,-(CH,&
0.045
72
0.108
32.5
hexyi PEI/silica gel
CBa-WW4-CW-
0.13
19
benzyl PElfsilica gel
&HZ--
0.114
28
I.2
lo
20
30
40
50
60
70
80
)
,
I
I
I
I,
1
2
3
4
5
Time (minutes)
I1
6
7
I
8
I
910
Number of uses
Fig. 8. Comparison of the hydrophobic Pd~PEI/silica gel catalysts. The assay mixture consisted of,EtOH (1.5 ml), formic acid (0.33 ml) and water (0.5 ml). The substrate used was Cbz-Gly-O-t-Butyl. 1% Pd/PEI/glutaraldehyde/silica gel catalyst A; 1% Pd/PEI/ silica gel catalyst 0; 1% Pd/hexyl/PEI/silica gel catalyst A; 1% Pd/benzyl/PEI/silica gel catalyst R Fig. 9. Demonstration of the stability of Pd/PEI/siIica nitrobenzene in methanol at atmospheric pressure.
gel used in the hydrogenation
of
Properties Pd/PEI/silica gel catalyst has a surface area of 500 m2 g-’ (BET) (Table 2). The palladium content was 1.05%. In contrast to the Pd/PEI/silica beads, the Pd/PEI silica gel can be used in a Parr shaker and in reactors with overhead stirring. In both cases, the catalyst can be recovered easily by filtration. Use of a magnetic stirrer results in disintegration of the gel to a fine powder. The Pd/PEI/silica gel catalyst will efficiently reduce nitrobenzene to aniline. After ten uses the catalyst retained full activity (Fig. 9). When the Pd~PEI/silica gel catalyst was reused with formic acid, however, a rapid decrease in activity was observed. A significant amount of activity was restored after treatment of the used catalyst with NaBH+ Discussion It was our goal to prepare an inorganic/organic composite with high surface area and metal binding capacity with the hope of preparing more effective and/or selective hydrogenation catalysts. The readily modifiable amino groups of PEI and the affinity of PEI for various metal ions attracted us to PEI/silica conjugates. Two types of silica were selected - porous silica beads and silica gel. Klotz and co-workers [6] have prepared a number of PEI-based catalysts which show enzyme-like characteristics. Hydrophobic
13
derivatives of PEI containing alkylaminopyridine substituents are very effective catalysts of nitrophenylester hydrolysis, The hydrophobic cavity of cyclodextrins has been exploited by Breslow [7] in dramatic demonstrations of the enzyme-like behavior of cyclodextrin catalysts. In this study the production of apolar groups into the support surprisingly resulted in no rate enhancements in the hydrogenolysis of the Cbz-group of a neutral peptide reactant, Cbz-Gly-O-t-butyl. In theory, the matrix should have a strong affinity for the reactant and the positivelycharged product should be repelled by the catalyst which is also positively charged. The apolar groups were introduced prior to the attachment of metal. One explanation is that the most accessible chelation sites were blocked by the attachment of the hydrophobic substitutents. An alternate explanation is that the binding of reactant was too strong, which would be comparable to substrate/product inhibition in enzyme catalysis. Reactant tightly bound in the wrong orientation would be unreactive and also might limit access to other metal sites in the catalyst matrix. The catalysts which contain no hydrophobic substitutents have a number of features which suggest their use in lab-scale synthetic applications. Unlike palladium-on-carbon, the Pd/PEI silica catalysts have shown no pyrophoric behavior, Use of a filter aid is not necessary for either Pd/PEI silica beads or Pd/PEI silica gel. The catalysts can be separated from the product simply by decanting the supernatant solution. The reusability and stability of the catalysts are also attractive features. Finally, the possibility to perform hydrogenation reactions with formic acid or formate salts in polar solvents may be important in instances where the insolubility of reactants or products is a problem.
Acknowledgement This work was supported U.S.A.
by a grant from
Dow Chemical
Company,
References 1 L. E. Davis, in R. L. Davidson and M. Sittig (eds.), Water-Soluble Resins, Reinhold, New York, 1968, p. 216. 2 W. E. Meyers and G. P. Royer, J, Am. Chem. Sot., 99 (1977) 6141; D. R. Coleman and G. P. Royer, J. Org. Chem., 45 (1980) 2268. 3 K. Watanabe, Wen-Shiung Chow and G. P. Royer, Anal. Biochem., 12 (1982) 155. 4 U.S. Pat. 4 326 009 (1982) to G. P. Royer. 5 S. J. Moore, J. Biol. Chem., 243 (1968) 6281. 6 T. Delaney, E. J. Wood and I. M. Klotz, J. Am. Chem. Sot., 104 (1982) 799;M. A. Hierl, E. P. Gamsen and I. M. Klotz, J. Am. Chem. Sot., 101 (1979) 6020. 7 R. Breslow, Science, 218 (1982) 532.
PALLADIUM/POLYETHYLENIMINE
CATALYSTS
G. P. ROYER*, WEN-SHIUNG CHOW and KIMI S. HATTON Department of Biochemistry, OH 43210 (U.S.A.) fReceived May 16,1984;
Ohio State University,
484 W. 12th Avenue, Columbus,
accepted October 5,19&Z)
Summary We report the preparation and evaluation of palladium catalysts made from polyethylenimine (PEI)/silica composites. PEI was adsorbed to either porous silica beads or silica gel, Following crosslinking, the material was leached with bass to increase the surface area and availability af the polymer. The PEI/siiicas rapidly chelate Pd2+ from solution. Reduction of the chelated metal ions can be accomplished with sodium borohydride. Pd/PEI/silica beads are used effectively in suspension with formic acid as the hydrogen donor; deprote~tion of Cbz-Glyeine-O-t-butyf (where Cbz-carbobenzoxy) is very rapid with this catalyst compared to p~adium on carbon. The Pdf PEI/silica gel catalyst can be used effectively with hydrogen gas for the reduction of nitrobenzene in methanol. Both catalysts are conveniently separated from product by simply decanting the supernatant solution. The catalysts (1% Pd) have shown no pyrophoric behavior and they are reusable. Hydrophobic derivatives of the catalysts were prepared with the hope that apolar reactants would be attracted to the metal sites with a concomitant enhancement of rate. The introduction of apolar groups into the catalyst matrix did not, however, result in a more effective catalyst compared to the catalyst made from the unmodified material.
Introduction Polyethylenimine (PEI) is a branched polymer obtained by the polymerization of aziridine: -
t CHD-I,NK
),
*Author to whom eorresporidence should be addressed at: Amoco Research Center, P.O. Box 400, Naperville, IL 60566, U.S.A. 0304~S102/85/$3,30
@ Elsevier Sequoia/Printed
in The Netherlands
The branching
may be represented
as follows:
The amine distribution is 25% primary, 50% secondary and 25% tertiary [ 11. We have described the immobilization of PEI on porous silica beads [ 2 ] and silica gel [3]. A three-step process is used to produce materials which we have termed ‘polymer ghosts’ (Fig, 1): first, PEI is adsorbed onto the inorganic particles; the adsorbed polymer layer is then chemically crosslinked; the composite is then leached to remove all or part of the inorganic material to provide a material with high surface area [ 4 1. Palladium catalysts can be prepared as shown in Fig. 2. The Pd2+ binds strongly to the amine support, and metal loadings of up to 5% can be achieved. The reduction of the palladium may be accomplished with sodium borohydride in water or organic solvent; aqueous formaldehyde is also effective. Palladium/PEI/silica beads and palladium/PEI/silica powder have been prepared with porous silica beads (surface area 52 m2 g-‘) and silica gel (500 m2 g-i) as the respective starting materials. Both catalysts are active with hydrogen or formic acid. In this paper, we describe their use in debenzylation reactions and in the reduction of aromatic nitro compounds. The catalysts are reusable, and readily settle out from suspension. Catalysts (1% Pd) have shown no pyrophoric behavior when used with organic solvents.
@ inorganic core
I
0
f--A \/
PEUSilica
bead
0
0 Pd/PEI/Silica catalyst
bead
Fig. 1. Preparation of PEIfsiiica beads. Fig. 2. Schematic diagram showing metal chelation and reduction to form Pd/P~I~sili~ bead catalyst.
3
PEI-‘ghosts’ attracted us because of their high surface area and metal chelating capacity. In addition, because the amino groups of the catalyst support are readily modifiable with straightforward chemistry, we felt that the system provided an opportunity to alter the environment of the metal. Since large rate enhancements have been observed as a result of the hydrophobic effect, one goal of this work was to prepare and evaluate hydrophobic catalysts. In theory, the rate of reaction involving such catalysts could be changed according to the hydrophobic character of the solvent. Solvent compositions which were just hydrophobic enough to dissolve the reactant would be desirable in this case; the reactant would tend to leave the solvent and bind to the catalyst support in the vicinity of the metal. Also, negatively-charged reactants would be attracted to the catalyst and positively-charged products repelled, in analogy to some enzyme reactions. Experimental
section
Materials PEI was purchased from Cordova Chemical Company as Corcat@ (MW 60 000, 33% PEI in water). Xama@-2, a polyfunctional aziridine crosslinking agent, was also obtained from Cordova. Silica gel (Grade 923) was from Davison/W.R. Grace, and silica beads were supplied by Corning (Code Number 691952,35-40 mesh, average pore diameter 275 A). PEI adsorption to silica beads The PEI binding capacity of silica beads was determined in the following manner. A sample of silica (0.1 g) was placed into a 12 ml screw-cap tube with methanol (about 7 ml). The tubes were placed in a heated desiccator and a vacuum was applied for removal of trapped air. The methanol was removed with a pipet fitted with nylon net. Five ml of the desired PEI solution were then added, and the tube was tightly capped. The PEI/silica suspensions were rotated end-over-end for 3 h and the supematant solution was removed. In the experiments which lead to the results shown in Fig. 3, 8.07.06.05.0 4.0 -
IPEII in MeOH (mg/ml)
Fig. 3. The binding of PEI to silica beads. One g of silica’beads was equilibrated with methanolic solutions of PEI. The beads were then washed twice with methanol, dried, and then ground to a fine powder. The PEI content was determined by use of ninhydrin reagent [5] 0.
4
the beads were washed once with methanol prior to the determination of primary amine content. In this manner, loosely bound PEI would be removed. Methanol (5 ml) was added, and the mixture was agitated by vortex mixer for 5 s, The wash was removed, and the beads were dried in a heated desiccator and then ground to a fine powder for the determination of primary amine content by the ninhydrin test [ 51. Preparation of PEIhilica beads PEI/silica beads were synthesized using a rotary evaporator (Buchi, RE120). Fifty grams of silica beads were placed in a 1000 ml round-bottom flask, and 200 ml of PEI/meth~ol were added. Trapped air was removed by lowering the pressure while the flask was rotated at maximum speed at room temperature. Methanol was then evaporated (35 “C). The resulting PEI beads were dried in a heated vacuum desiccator. Twenty g of PEI/silica beads (4 wt.%), were placed in a 250 ml round-bottom flask, and 50 ml of 0.5% glut~~dehyde in THF were added. The flask was placed on the rotary evaporator and rotated at l/4 maximal speed for an additional 30 min. The THF solution was removed by suction with a gas dispersion tube and replaced with 100 ml of aqueous NaBH4 (1%). The flask was rotated at l/4 maximal speed for 1 h. The borohydride solution was decanted and 100 ml of aqueous formic acid (15%) was added. After rotation for 1 h at l/4 maximal speed, the formic acid solution was decanted and 5 N NaOH (200 ml) was added. After leaching the preparation for 1 h at l/4 maximum rotation speed, the beads were washed to neutrality with water and dried in a vacuum desiccator. All of the above operations were performed at room temperature. Ad~rption of palladium The binding of palladium by the PEI composites can be followed spectrophotometrically (375 nm). A palladium acetate stock solution was prepared by dissolving PdCl* (0.2 g) in 2 ml of concentrated HCl with heating. Addition of sodium acetate solution (48 ml, 15% w/v NaAc- 3Hz0) yields the stock solution which contains 2.5 mg of palladium per ml. To determine the adsorption rate, 1 g of PEI/silica composite was shaken on a wrist-action shaker with 4 ml of palladium acetate stock solution in a 25 ml Erlenmeyer flask. Samples were withdrawn at timed intervals for spectrophotometric analysis. The control experiment shown in Fig. 4 was performed with silica beads which were subjected to the procedure for preparing PEIfsilica beads from which the PEI was omitted. Sodium borohydride reduction in various solvents Water and several organic solvents were used in the reduction step of catalyst preparation. The concentrations of NaBHe in the solvents were as follows: 0.05 g ml-’ DMF, 0.025 g ml-’ diglyme, 0.02 g ml-’ ethanol and 0.25 g ml-’ water. These solutions were made by cooling the solvents below 5 “C in an ice-water bath and adding the specified amount of NaBH+
5
Several 1 g samples of support were placed in 25 ml Erlenmeyer flasks. After the PdZ+ was adsorbed from the PdCl*-NaAc solution, the supernatant was removed by suction through a pipet fitted with polyester net. The Pd2+ PEI/silica beads were washed two times (10 ml each time) with the solvent chosen for the reduction, and then 1 ml of the solvent was added to the beads. The flask was cooled to below 5 “C. The solutions of NaBHe in the chosen solvent were maintained at the same temperature. Reduction of the Pd2+ was carried out by pipetting an appropriate volume (50 mg NaBH4 g-i support) of the cold borohydride solution into the flask followed by a vigorous swirling motion. Reduction was allowed to continue for 15 min with agitation of the flask about every 5 min. Procedure for the reduction of Pd2’/silica beads in water using NaBH4 After the Pd2+ was adsorbed on the support, the liquid phase was removed from the solid beads (1 g) by suction through a pipet fitted with polyester net. The beads were washed with water two times (15 ml each). One ml of water was then added and the suspension was cooled in an icewater bath to between 0 and 2 “C. A solution of NaBHe in water was made by dissolving sodium borohydride in water (precooled to 0 - 4 “C). For the reduction of 1 g of support, NaBH4 (150 mg) was dissolved in 3 ml of cold water. One ml of this solution was added to the Pd?+/silica beads in water, and the beads were swirled rapidly for about 1 min. The beads were then allowed to sit in an ice-water bath for 0.5 h with intermittent swirling. At the end of this time, the supernatant was removed. The blackened beads were then washed twice with 10 - 15 ml of water. One ml of water was added and the flask was cooled in an ice-water bath. Reduction was repeated by adding 1 .O ml of the borohydride solution followed by a vigorous swirling motion. The bea.ds were allowed to sit in an ice-water bath for 30 min with intermittent agitation, washed four times with water (15 ml each time), and then washed two times with methanol (10 - 15 ml each time) prior to drying in a vacuum desiccator. Reduction in this fashion requires 100 mg NaBHe g-’ of beads. Preparation of octanoyl/PEI/silica beads Three g of PEI/glutaraldehyde/silica beads were placed in a 100 ml round-bottom flask, and 25 ml of 20 vol.% triethylamine in DMF were added. A vacuum was applied for 30 min for the removal of trapped air. The triethylamine solution was removed by decantation and 0.28 g of octanoyl chloride in 10 ml of DMF were added. An additional 1 ml of 20% triethylamine in DMF was added. The suspension was rotated at l/4 maximal speed on the rotary evaporator for 48 h at room temperature. The modified support was washed with 20% TEA in DMF, DMF, methanol, water and methanol and dried in a heated vacuum desiccator. Synthesis of octyl/PEI/silica beads Two g of PEI silica beads were placed in a 100 ml round-bottom flask and triethylamine/HMPA (20%, 25 ml) was added. A vacuum was applied
6
for the removal of trapped air as the flask was slowly rotated on the rotary evaporator. The supernatant solution was removed by suction with a gas dispersion tube, and the procedure was repeated. After removing the second wash, 10 ml of HMPA was added. To this suspension was added 1.23 g of octyl bromide and 1.29 g of tri~thylamine. The mixture was rotated at l/4 maximal speed on the rotory evaporator for 72 h at 50 “C. The HMPA solution was removed by suction through a gas dispersion tube, and the modified beads were washed with additional 20% triethylamine/HMPA, HMPA, and methanol and dried in a heated vacuum desiccator. Preparation 0 f PEI~sili~agel Silica gel (10 g) was mixed with the PEI stock solution (0.5 g PEI/lO ml MeOH). The methanol was removed with a rotary evaporator. The silica was then washed briefly with cold methanol to remove extraneous PEI and dried in a vacuum desiccator. Twenty-five ml of 1% (wt/v) glutaraldehyde in water was added to the silica gel and the suspension rotated at room temperature for 30 min. The glutaraldehyde solution was replaced with 25 ml of 1% PEI in methanol and rotated for an additional 30 min. The PEI solution was poured off, and NaBH4 (300 mg in 25 ml MeOH) was added. After rotation for 30 min, the preparation was washed with water, methanol and dried in a vacuum desiccator. Preparation of Pd/PEI/silica gel A palladium stock solution was made by mixing 1 ml of 1 N HCl with 85 mg PdC12 and heating to dissolve the mixture. Ten ml of a 15% solution of NaAc* 3Hz0 was added. This palladium stock solution (4.4 ml) was added to 2 g of PEIfsilica gel. Uptake of Pd2+ was complete within 10 min. The preparation was then reduced with 300 mg of NaBH, in 10 ml of cold MeOH. After washing with water, 10% formic acid/water and methanol, the catalyst was dried in a heated vacuum desiccator. Preparation of PEI/Xama@/silica gel PEI (10 g, 33% aqueous) was mixed with 0.3 g of Xama@-2 in 10 ml of MeOH and refluxed for 10 min. The volume was then adjusted to 50 ml with MeOH. Five ml of the PEI-Xama@ solution were mixed with 10 g of silica gel suspended in 100 ml of methanol. The mixture was stirred with an overhead stirrer and heated on a boiling water bath for 15 min. Methanol was then evaporated, and the PEI-silica was repeatedly suspended in water until the decanted wash water gave a negative ninhydrin test. The support was dried in a heated vacuum desiccator. Preparation of hydrophobic PEI/Xama@ silica gel supports (1) Acylation: PEI/Xama@ silica gel (5 g) was washed twice with 2% triethylamine in DMF (50 ml). Enough DMF was added to cover the support. To this suspension was added ~-nitrophenyl caproate (0.9 g) and triethylamine (0.13 ml). The reaction mixture was continuously rotated for
24 h at 5 “C. At the end of this time, the silica gel was filtered, washed with methanol and dried in a vacuum desiccator. (2) Reductive alkylation: (a) Aqueous buffer-methanol mixture. PEI/ Xama@/silica gel was mixed with hexanal (50 ~1) in a mixture of 0.1 M borate buffer (25 ml, pH 8.5) and methanol at 4 “C. NaBHa (70 mg total) was added in six equal portions over a period of 1 h with occasional agitation. The support was then washed with water and methanol, and then dried in a heated vacuum desiccator. The decrease in primary amine content was 14%. (b) In methanol. PEI/Xama*/silica gel (2 g) was washed with 2% trie~ylamine in DMF (50 ml) and suspended in 10 ml of meth~ol. To this suspension was added hexanal (340 ~1) in 2 ml of ethanol. The suspension was agitated occasionally. After 30 min, NaBHe (25 mg) was added in five equal portions over a period of 1 h. The support was then washed with water and methanol, and dried in a vacuum desiccator. The decrease in primary amine content was 32.5%. (3) Alkylution: PEI/X~a~ silica gel was suspended in 10 ml of DMF containing 100 ~1 of triethylamine. To this suspension was added 100 ~1 of benzyl bromide, and the mixture was rotated for 1 h at 90 “C. The material was washed with methanol and dried in a vacuum desiccator. The decrease in primary amine content was 28%. ~epa~tion of hyd~phobi~~PEI~~ilica bead and silica gel~palladium catalysts Hydrophobic/PEI/silica catalysts were synthesized by the same general method as underivatized PEI/silica catalysts. The only change in the procedure was the amount of time the hydrophobic derivatives were exposed to solutions of Pd*+. The underivatized PEI/silica beads and silica gel decolorized solutions of Pd*’ within 5 - 10 min, while the hydrophobic derivatives required 24 - 48 h. Since the hydrophobic PEI/silicas tend to float in aqueous solution, the suspension was rotated to ensure maximum exposure of the PEI/silica to the Pd*+ solution. After the supernatant solution of the Pd2+ became colorless, the preparation was reduced with sodium borohydride as previously described. Repeated use of palladium/PEI/~ilica catalysts in formic acid A sample of catalyst (0.2 g) was placed in a 25 ml Erlenmeyer flask and was assayed for activity using Cbz-Gly-O-t-butyl as the substrate in HCOOH:EtOH:H,O (assay described below). After about 60 - 70 min, the assay mixture was removed with a pipet fitted with polyester net. The catalyst was washed 4 times with 15 ml of methanol and dried in a vacuum desiccator. The Cbz-Gly-C-t-butyl assay was performed with this 0.2 g sample 10 times and the ti,* was determined for each run. Cbz--GTy+3-t-butyl assay A stock solution of Cbz-Gly-U-t-butyl stored at 4 “C. A 1:5 HCOOH:H,O solution
in ethanol was made and was prepared fresh daily. The
assay mixture consisted of 3.5 ml of HCOOH:EtOH:H,O and 0.12 g of CbzGly-O-t-butyl (2 ml of the HCOOH:HzO solution and 1.5 ml of the substrate in EtOH solution). The assay mixtures were agitated on a wristaction shaker at maximum speed. The shaking motion of the flask can be described as a 20” detection from the horizontal with approx~ately 240 excursions per minute. The distance travelled perpendicular to the horizontal was 2.5 cm. A weighed sample of catalyst was placed in a 25 ml Erlenmeyer flask and secured on the wrist-action shaker, The assay mixture was delivered to the flask (t = 0), the flask was stoppered with a perforated cork, and the speed of shaking was brought to the m~imum. Samples (4 ~1) were taken at timed intervals, and the extent of reaction was determined by ninhydrin analysis. Hydrogenation of nitrobenzene/re-use of the Pd/PEUsilica gel Nitrobenzene (10.3 ml, 0.1 mol), methanol (90 ml), and 2.1 g of 1% Pd/PEI/glu~~dehyde/sili~a gel were added to a 500 ml 3-neck roundbottom flask equipped with an overhead stirrer. Hydrogenation was performed at atmospheric pressure. The flow of hydrogen gas was fixed at a constant rate with a Gilmont flowmeter (0.5 1 min-‘, calibrated by air). The reaction was begun at room temperature. With no external temperature control the reaction mixture warmed to a temperature of about 56 “C. At timed intervals, aliquots (10 ~1) were removed and diluted with 5 ml of methanol and 95 ml of water. The samples were analyzed spectrophotometrically (220 - 320 nm). The stability test (reuse of 1% Pd/PEI/silica gel) was performed by using the same sample of catalyst 10 times, At the end of the reaction, the catalyst was filtered, washed with methanol, dried and recycled.
Results Pd/PEI/silica beads Preparation In order to arrive at optimal conditions for the PEI adsorption step, we studied the binding of PEI as a function of polymer concentration (Fig. 3). In this study, silica beads were equilibrated with methanolic solutions of PEI. Weakly-bound PEI was removed with a methanol wash prior to the determination of bound polymer. The saturation point is about 4 wt.% PEI/ silica. Crosslink~g is best done in a solvent that does not dissolve PEI; THF works well for this purpose. Glutaraldehyde and XamaQ (a multi-functional aziridine) are effective crosslinking agents. Uptake of Pd 2+ by PEI/silica beads is quite rapid (Fig. 4). PEI/silica (1 g) can adsorb 10 mg of palladium in less than 10 min. Adsorption of Pd2+ onto control beads (no PEI content) is not significant. Thus, binding of Pd2+ to the composite occurs exclusively through infraction with the amine ligand .
9
0 0
Control 0ctsnoyl
A
octyi
O.l-
h-_-s 5
10
^
c
=
0
15
20
25
30
5
Time (minuted
15
30
45
50
75
Time (minutes)
Fig. 4. Uptake of Pd 2+ by PEI/silica beads (0) and control silica beads containing no PEI (0). Fig. 5. Comparison of hydrophobic Pd/PEI/silica bead catalysts and unmodified Pd/PEI/ silica bead catalysts. The activity of the catalyst was measured using the removal of’the Cbz-group from Cbz-Gly-0-t-Bu in HCOOH:EtOH:water as described in the text. The assays were performed at 23 “C. Pd/PEI/silica beads 0; Pd/octanoyl PEI/silica beads 0; and Pdloctyl PEI/silica beads A.
TABLE 1 The primary amine content of hydrophobic PEI/silica sample
PEI/silica bead
PEI/silica beads
Group incorporated
-
Primary amine content (meq g+)
Modification of primary amine
0.22 - 0.30
-
(%)
0 octanoyl PEI/silica bead
CH3-(CH2&-
0.145
46
octyl PEI/silica bead
CHs-(CH2)s-CH2-
0.187
15
lauryl PEI/silica bead
CHs-(CH,),o--CH,-
0.194
35
Borohydride reduction of the Pd2+/PEI/silica beads can be done in a number of organic solvents. Double reduction with aqueous borohydride (5 g NaBH,/lOO g of beads) produces an acceptable catalyst.
10
Hydrophobic substitution of the PEI/silica beads was done in order to augment interaction of apolar reactants with the catalyst support (Table 1). Reaction rates with the hydrophobic catalysts were not as fast as those for unsubstituted catalyst beads {Fig. 5). Properties Pd/PEI/silica beads made by the procedure reported here have a surface area of 47 - 52 m2 g-’ (BET) (Table 2). The palladium content is 1.09% in good agreement with the theoretical value. The beads can be used in a packed bed reactor. Suspension of the beads by shaking is also effective. The beads settle quickly from suspension, which permits direct decantation of the. product. solution. Use of a magnetic stirrer results in rapid destruction of the beads. Pd/PEI/silica beads effectively catalyze the removal of the Cbz group’vvith formic acid as the hydrogen donor:
Pd/PEIjSiOz + HCOIH
*HNy’x
+ toluene
+ COZ
0 The Pd/PEI catalyst beads are more effective than palladium-on-carbon (1% Pd) with formic acid as the hydrogen donor (Fig. 6). With hydrogen gas using Cbz-Asp-Phe-OME, palladium-on-carbon is slightly more effective than the p~ladium beads (data not shown). Repeated use of the Pd/PEIf silica bead catalyst using formic acid as the hydrogen donor results in some loss of activity (Fig. 7). The catalyst may be partially reactivated by treatment with NaBH,. Pd~PEI~sili~ugel. ~epar~~io~ The PEI/silica gel is synthesized by adsorbing PEI to the extent of 5% onto silica gel and then washing with cold methanol. After drying the coated gel, crosslinking ii5 accomplished by treatment with aqueous glutaraldehyde. TABLE 2 Properties of Pd/PEI/silica catalysts Sample
BET surface area (m2 g-l 1
Cumulative pore volume (cm3 g-l)
Average pore radius (h
silica beads silica gel
47 499
0.70 0.30
265 14
11
!a 40 30 20 10 ~
”
10
20
30
40
12
606070
I
I
I
I
I
I
I
1
3
4
5
6
7
8
9
VI
Number of uses
Time (minutes)
Fig. 6. Comparison of 1% Pd-on-carbon and 1% Pd/PEI/silica beads in the removal of the Cbz group from Cbz-Gly-G-t-Bu in formic acid. Pd/PEIlsiliea beads 0; Pd/C Q Fig, 7. Reuse of the PdfPG/silica bead catalyst in formic acid/debloeking G-t-butyl.
of Cbz-Gly-
Using organic solvents in the crosslinking step tends to cause agglomeration of the gel particles. Uptake of Pd2+ by the PEI/silica gel is rapid and comp~able to the rate of uptake by PEI/silica beads. Adsorption is complete within 5 - 10 min; the extent of palladium uptake is greater than 95%. Reduction with borohydride can be accomplished with solvents such as methanol, ethanol and water. Hydrophobic derivatives of PEI/silica gel were made for two reasons for evaluation of the effects on the palladium catalyst activity and for chromato~aphic applications. The degree of hydrophobic substitution of the PEI/silica gel is shown in Table 3. Reaction rates with hydrophobic PEI/ silica gel catalysts were not as fast as those for the corresponding unsubstituted Pd/PEI/silica gel catalysts (Fig. 8). TABLE 3 Primary amine content of hydrophobic PEI/silica gels PEI/silica sample
Group incorporated
PEl/siliea gel
0
Primary amine content (meq 9’1
Modification of primary amine (%l
0.16
-
hexanoyl PEI/silica gel
CH,-(CH,&
0.045
72
0.108
32.5
hexyi PEI/silica gel
CBa-WW4-CW-
0.13
19
benzyl PElfsilica gel
&HZ--
0.114
28
I.2
lo
20
30
40
50
60
70
80
)
,
I
I
I
I,
1
2
3
4
5
Time (minutes)
I1
6
7
I
8
I
910
Number of uses
Fig. 8. Comparison of the hydrophobic Pd~PEI/silica gel catalysts. The assay mixture consisted of,EtOH (1.5 ml), formic acid (0.33 ml) and water (0.5 ml). The substrate used was Cbz-Gly-O-t-Butyl. 1% Pd/PEI/glutaraldehyde/silica gel catalyst A; 1% Pd/PEI/ silica gel catalyst 0; 1% Pd/hexyl/PEI/silica gel catalyst A; 1% Pd/benzyl/PEI/silica gel catalyst R Fig. 9. Demonstration of the stability of Pd/PEI/siIica nitrobenzene in methanol at atmospheric pressure.
gel used in the hydrogenation
of
Properties Pd/PEI/silica gel catalyst has a surface area of 500 m2 g-’ (BET) (Table 2). The palladium content was 1.05%. In contrast to the Pd/PEI/silica beads, the Pd/PEI silica gel can be used in a Parr shaker and in reactors with overhead stirring. In both cases, the catalyst can be recovered easily by filtration. Use of a magnetic stirrer results in disintegration of the gel to a fine powder. The Pd/PEI/silica gel catalyst will efficiently reduce nitrobenzene to aniline. After ten uses the catalyst retained full activity (Fig. 9). When the Pd~PEI/silica gel catalyst was reused with formic acid, however, a rapid decrease in activity was observed. A significant amount of activity was restored after treatment of the used catalyst with NaBH+ Discussion It was our goal to prepare an inorganic/organic composite with high surface area and metal binding capacity with the hope of preparing more effective and/or selective hydrogenation catalysts. The readily modifiable amino groups of PEI and the affinity of PEI for various metal ions attracted us to PEI/silica conjugates. Two types of silica were selected - porous silica beads and silica gel. Klotz and co-workers [6] have prepared a number of PEI-based catalysts which show enzyme-like characteristics. Hydrophobic
13
derivatives of PEI containing alkylaminopyridine substituents are very effective catalysts of nitrophenylester hydrolysis, The hydrophobic cavity of cyclodextrins has been exploited by Breslow [7] in dramatic demonstrations of the enzyme-like behavior of cyclodextrin catalysts. In this study the production of apolar groups into the support surprisingly resulted in no rate enhancements in the hydrogenolysis of the Cbz-group of a neutral peptide reactant, Cbz-Gly-O-t-butyl. In theory, the matrix should have a strong affinity for the reactant and the positivelycharged product should be repelled by the catalyst which is also positively charged. The apolar groups were introduced prior to the attachment of metal. One explanation is that the most accessible chelation sites were blocked by the attachment of the hydrophobic substitutents. An alternate explanation is that the binding of reactant was too strong, which would be comparable to substrate/product inhibition in enzyme catalysis. Reactant tightly bound in the wrong orientation would be unreactive and also might limit access to other metal sites in the catalyst matrix. The catalysts which contain no hydrophobic substitutents have a number of features which suggest their use in lab-scale synthetic applications. Unlike palladium-on-carbon, the Pd/PEI silica catalysts have shown no pyrophoric behavior, Use of a filter aid is not necessary for either Pd/PEI silica beads or Pd/PEI silica gel. The catalysts can be separated from the product simply by decanting the supernatant solution. The reusability and stability of the catalysts are also attractive features. Finally, the possibility to perform hydrogenation reactions with formic acid or formate salts in polar solvents may be important in instances where the insolubility of reactants or products is a problem.
Acknowledgement This work was supported U.S.A.
by a grant from
Dow Chemical
Company,
References 1 L. E. Davis, in R. L. Davidson and M. Sittig (eds.), Water-Soluble Resins, Reinhold, New York, 1968, p. 216. 2 W. E. Meyers and G. P. Royer, J, Am. Chem. Sot., 99 (1977) 6141; D. R. Coleman and G. P. Royer, J. Org. Chem., 45 (1980) 2268. 3 K. Watanabe, Wen-Shiung Chow and G. P. Royer, Anal. Biochem., 12 (1982) 155. 4 U.S. Pat. 4 326 009 (1982) to G. P. Royer. 5 S. J. Moore, J. Biol. Chem., 243 (1968) 6281. 6 T. Delaney, E. J. Wood and I. M. Klotz, J. Am. Chem. Sot., 104 (1982) 799;M. A. Hierl, E. P. Gamsen and I. M. Klotz, J. Am. Chem. Sot., 101 (1979) 6020. 7 R. Breslow, Science, 218 (1982) 532.