ELSEVIER Desalination 147 (2002) 301-306

DESALINATION

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Homogeneous catalyst separation and re-use through nanofiltration of organic solvents

Dinesh Nair, a Satinder Singh Luthra, a Justin T. Scarpello, a Lloyd S. White, b Luisa M. Freitas dos Santos c, Andrew G. Livingston a'*

aDepartment of Chemical Engineering, Imperial College, London SW7 2BY,, UK Tel. +44 (20) 7594-5582; Fax: +44 (20) 7594-5604; email: a.livingston@ic.ac.uk

bW.R Grace & Co.-Conn., 7500 Grace Drive, Columbia, MD 21044, USA CGlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, Essex CM19 5A W, UK

Received 30 January 2002; accepted 13 February 2002

Abstract

The separation of reaction products from catalysts is a major problem existing in many forms of homogeneous catalysis, including phase transfer catalysis and transition metal catalysed reactions. This study describes a new and generic approach to solving this separation problem using solvent resistant nanofiltration (SRNF) membranes. Data for SRNF separation of a phase-transfer catalyst (PTC), and a Heck reaction transition metal catalyst (TMC), from their respective reaction media is presented. SRNF was used to retain each catalyst from the reaction solvent and, when applied in a coupled reaction-separation system, allowed several subsequent catalyst recycles and re-uses. PTC rejection was high (99+%) whether SRNF was applied to pre- or post-reaction mixtures, and no reaction rate decline was observed for two consecutive catalyst recycles. TMC rejection, while 96% for pre-reaction mixtures, dropped to 90% for post- reaction mixtures and reaction rate decline was observed for four consecutive catalyst recycles. The clear difference between the two systems is the much higher stability of the PTC due to a less demanding catalytic cycle. The need for stable catalytic systems for effective generic use of this technology in homogeneous catalysis is highlighted.

Keywords: Homogeneous catalysis; Nanofiltration; Catalyst recycle

1. I n t r o d u c t i o n

Catalytic organic synthesis has become a major focus for developing cleaner processes

*Corresponding author.

within the sphere of Green Chemistry [1,2]. Examples of this include use of phase-transfer catalysts (PTCs) and transition metal catalysts (TMCs). PTCs avoid use of polar aprotic solvents for reactions involving a water-soluble nucleo- philic reagent and an organic soluble electro-

Presented at the International Congress on Membranes and Membrane Processes (ICOM), Toulouse, France, July 7-12, 2002.

0011-9164/02/$- See front matter © 2002 Elsevier Science B.V. All rights reserved PII: SO0 I 1 - 9 1 6 4 ( 0 2 ) 0 0 5 5 6 - 8

302 D. Nair et al. / Desalination 147 (2002) 301-306

philic reagent [3]. Similarly, TMCs can provide faster reactions and fewer steps than using stoichiometric reagents (e.g., the Heck reaction provides the only single-step route for coupling aryl halides to olefins [4]). A major drawback of such catalysis is the extensive (and usually destructive) post-reaction work-up that is needed to remove the catalyst from the reaction products [5]. Furthermore, until recently, no effective membrane-based catalyst recovery method existed that was stable for operation in an organic solvent environment.

The recent development of solvent resistant nanofiltration (SRNF) membranes has made the non-destructive, energy-efficient separation and concentration of re-usable catalyst from products feasible [6-9]. Nanofiltration membranes are selective between organic synthesis catalysts, which are usually relatively large (>450 Da), and reaction products that are substantially smaller. In the generic approach for coupled reaction- separation (Fig. 1), a post-reaction mixture (containing a bulky catalyst, smaller product and unreacted reactants in an organic solvent) can be fed to a SRNF membrane which, under applied pressure, selectively rejects and retains catalyst molecules whilst allowing permeation of

products and reactants. The catalyst-rich retentate can then be recycled back to the reactor and topped up with fresh reactants and solvent; in this way, the reaction can be reinitiated and the catalyst re-used multiple times.

One PTC and one TMC model reaction were chosen to show the generic applicability of the coupled reaction-separation technology to homogeneous catalysis. The model PTC reaction effected the conversion of bromoheptane to iodoheptane (Fig. 2) in toluene as an organic phase, using an aqueous phase containing potas- sium iodide, catalysed by tetraoctylammonium bromide (TOABr). This is a common example of a nucleophilic, aliphatic substitution reaction. The Heck coupling of iodobenzene with styrene, to produce t rans - s t i l bene (Fig. 3), was selected as the TMC model reaction, catalysed by {bis- (acetato)bis(triphenylphosphine)palladium(II)}.

In both cases, SRNF was used to separate the post-reaction mixture into a small, catalyst-rich stream (for return to the next reaction) and a larger, catalyst lean product stream. The large size difference between catalyst and product in the model reactions was deliberate to maximise selectivity of the membrane during each filtration.

J Reactor [ Post-rxn J SRNF " - -

Rxnfeed 17 I mixture ~ membrane ]

Br-C7HI5 o~g + Klaq ~,rc > I-C7HI5 o~g + KBraq

Catalyst-rich retentate recycle

Product-rich permeate

Bromoheptane Iodoheptane MW 1"/9 MW 226

Iodobenzene Styrene tr~ns-stilbene MW 204 MW 104 MW 180

C C ) CH -NLCH C )6C C (C ) CH3 TOABr MW 546

I I

Heck catalyst MW 749

Fig. 1. Schematic of coupled reaction- separation system.

Fig. 2. PTC reaction for con-version of bromoheptane to iodoheptane.

Fig. 3. TMC Heck reaction for synthesis of trans-stilbene.

D. Nair et aZ / Desalination 147 (2002) 301-306 303

2. Experimental

2.1. Coupled reaction-separation procedure

Reactions were performed in thick-walled reactors fitted with a screw-on sample cap and a Teflon-coated self-sealing disk. The desired masses of reactant were weighed or pipet-ted into the reactor and the volume was made up to the reaction volume with the desired solvent. Nitrogen gas was bubbled through the reactor to mix the contents until all solids had dissolved. The reactor was placed in a stirred oil bath controlled at the reaction temperature to within 1 °C. An initial sample was taken using a needle and 1 mL syringe for immediate GC analysis [Shimadzu GC-14A gas chromatograph with a flame ionisation detector (FID) and a Megabore column 25 m long and 0.23 mm inner diameter with a BP 1 (SGE, Australia) stationary phase]. Subsequent sampling was carried out at various recorded intervals during the reaction period until between 95 and 100% conversion of reactant had been attained. The reaction was then quenched and the organic post-reaction mixture was trans- ferred under nitrogen from the reactor to the SRNF cell. A stainless steel SEPA ST pressure cell (Osmonics, CA., USA) was used for this study. An operating pressure of 30 bar was used for all filtration experiments. 90% of the post- reaction volume (85% for the TMC system) was permeated across the polyimide Starmem 122 SRNF membrane (W.R. Grace & Co., MD, USA) [ 10] into a collection receptacle. Both retentate and permeate were sampled for GC analysis. Based on these analyses, the retentate was topped up with fresh reactants and solvent. This new feed mixture containing the recycled catalyst was transferred back to the reactor and the reaction was re-initiated.

2.2. PTC reaction conditions

Aqueous phase KI (10.1 g, ! eq) made up to 40 mL with 1-120; organic phase bromoheptane

(3.6 g, 1 eq) and TOABr (1.09 g, 0.1 eq), made up to 40 mL with toluene; the biphasic system was heated to the reaction temperature (50°C).

2.3. TMC reaction conditions

Iodobenzene (2.7 mL, 1.25 eq) styrene (2.32 mL, 1 eq), triethylamine (2.82 mL, 1 eq), H20 (1.485 mL, 5.5 vol%), Heck catalyst {Pd(OAc)2(PPh3)2} (0.0485 g, 0.004 eq) and P(o- tol)3 (0.079 g, 0.016 eq) were made up to 27 mL with a 50:50 mixture of ethyl acetate and acetone; the system was heated to the reaction temperature (60°C).

An assessment was made of membrane com- patibility with these solvents, taking into account both physical membrane stability to prolonged solvent exposure and solvent flux [9]. In both solvents, very consistent solvent flux was obtained and no visible signs of membrane insta- bility (e.g., cracking) were observed for the same disk used repeatedly. This indicated that long- term membrane stability (relative to experiment duration) was high. Consequently, one disk was re-used for all consecutive filtrations in each coupled reaction-separation system.

The cumulative turnover number (TON) was calculated as the total moles of product synthe- sised over repeated reaction cycles per mole of catalyst initially added in the first run. The membrane performance was assessed in terms of flux and rejection. Flux was expressed as the volume permeated per unit area over a time period (l.m-2.h-I). Rejection of a species was defined as R = I00 ' [1- (Cp/C,)], with Cp and Cr representing final permeate and retentate concen- trations of that species per filtration. An R value of 100% corresponds to complete retention of a species and 0% to no separation. PTC concen- trations were measured using GC, while Pd concentrations in the TMC were measured by AAS (Perkin-Elmer 1100B, oxy-acetylene flame at 2000°C).

304 D. Nair et al. / Desalination 147 (2002) 301-306

3. R e s u l t s

Separation of the homogeneous catalysts from a synthetic post-reaction solution (containing catalyst and product at expected post-reaction concentrations) was studied using the Starmem 122 polyimide membrane. The retention of the catalyst and relatively free permeation of the product are vital for this technique to work.

The membrane showed very good selectivity between the species in the PTC system, with a TOABr rejection of 99+% and 22% rejection of iodoheptane. The synthetic post-reaction filtra- tion conducted with the Heck TMC showed that a 96% catalyst rejection and 0% trans-sti lbene

rejection were occurring. Since significant retention of product did not occur in either system, both were considered suitable for testing with a real post-reaction mixture in the coupled reaction-separation system.

The results of coupled reaction-separation applied to the PTC reaction are illustrated in Fig. 4. Reaction 1, after 5 h of stirring at 50°C, yielded a 97% conversion of bromoheptane to iodoheptane. After quenching the reaction and permeating 90% of the post-reaction volume across the SRNF membrane, the PTC-rich retentate was recycled to the reactor for the next reaction. Reactions 2 and 3 were conducted in the same way, also run for 5 h each, and yielded 90% and 96%, respectively. This indicated no loss of catalytic activity over the three reactions. A catalyst loading of 10 mol% yielded a cumulative TON of 28. The selectivity of the membrane also appeared to improve: PTC rejection remained at 99+%, but mean iodoheptane rejection (calcu- lated over the three reactions) decreased to 12%. This was probably due to the accumulation of rejected iodoheptane in the system from successive filtrations. A control experiment was also run without any PTC, which showed no conversion after 6 h.

The coupled reaction-separation technique was then applied to the Heck reaction TMC

(Fig. 5). The abrupt discontinuity of the iodo- benzene conversion line at the end of reaction 1 represents a filtration, addition of fresh reagents and the start of reaction 2 at zero iodobenzene conversion. The first batch reached near complete conversion in about 3 h. In the subse- quent filtration, a Pd rejection of only 90% was achieved, with a 2% rejection of trans-stilbene;

membrane selectivity had become noticeably worse. Similar poor Pd rejections were observed after subsequent reactions, with a substantial reaction rate decline occurring; the reaction rate had fallen to below 20% of the initial value by the 4th catalyst recycle (which took 26 h). The sequence was arbitrarily stopped there. None- theless, with catalyst loadings of 0.4 mol% (based on styrene), a cumulative TON approach- ing 1200 was achieved during five consecutive reactions using membrane separation to enable recycling of the same catalyst between reactions.

Table 1 summarises the key system perfor- mance parameters for the PTC and TMC processes. The key difference between them is the large difference in Pd rejection between synthetic and post-reaction mixtures for the Heck TMC. This is most likely due to the inherent

Table 1 Performance comparison of PTC and TMC recycle systems

System performance PTC TMC parameter system system

Reaction solvent Toluene EA/AC/H~O Synthetic catalyst R, % 99+ 96 Synthetic product R, % 22 0 Mean post-reaction 99+ 90

catalyst R, % Mean post-reaction product 12 2

R, % Mean solvent flux, I.m~.h - t 14 32 No. of recycles (TON) 2 (28) 4 (1220) Reaction rate decline None Substantial

D. Nair et al. / Desalination 147 (2002) 301-306 305

0,6

05

~ 0.4

03 0 u 0,2

0.1

l~t iol i i

l)ta~

I I

0 2 4

Reaction2

I I

0 2 4 0 2 4

Fig. 4. Evolution of bromoheptane and iodoheptane concentration over time in the reaction catalysed by TOABr [6].

100 I 4, '~ .' i /

i / /.° : 4t : O, n r

Z s o ;' / / , . . - ' ~ t i i * / a.o .... 70 * ta" : / i / / i)~" /

t i ,' i~ / i i '° ' .

• t " , i / / '~o 40 j .~ , i i /

. li i , I 20 / i J#7 i' " / ' l * Conversion

"> 1°rE ~ o ~ i i ~ :a::::!70N ................ o

0 5 10 15 20 25 30

1400

1200

1000 ,.. (D

E 800 = c

= 600 ="

0 C

400 i-.-

200

Time (hrs)

Fig. 5. Five consecutive reaction-separations for Heck OMC system [8].

instability of Pd in the Heck catalytic cycle. Although the exact catalytic mechanism is unclear, it is assumed that smaller Pd species are forming during the cycle, including Pd(0) entities that are both small enough to permeate the membrane and unstable enough to aggregate and precipitate as nanoclusters of Pd black [11 ]. As

active metal centres are lost from the system by either route, the reduced activity will be reflected in a lower reaction rate. The observed solvent flux in both systems is quite different, but it has been demonstrated that this is a property of the solvent-membrane interactions [9]. In both systems, a cleaner form of the product has been obtained for consecutive reactions, as the bulk of catalyst is removed by SRNF. This will reduce the downstream processing costs associated with removing the final remnants of catalyst. The same retained catalyst has also been re-used multiple times, introducing significant cost savings particularly for the TMC (with high metal and ligand values).

4. Conclusions

It has been demonstrated that the SRNF coupled reaction-separation technique can be generically applied to homogeneous catalysis provided that there is sufficient membrane selectivity between catalyst and product. The currently available range of SRNF membranes is small but growing, and already they are versatile enough to be used across a broad range of

306 D. Nair et al. / Desalination 147 (2002) 301-306

solvents. The key to successful application o f this technology to TMC systems is catalyst stability on a par with that evident in PTC systems, such that high reaction rates can be sustained over multiple consecutive reactions. This should enable the concept to be applied to a wider range of organic syntheses.

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