Industry perspective

FELIX SPINDLER*, PATRICK FURER AND JÜRGEN ROTZLER *Corresponding author Solvias AG, Roemerpark 2, CH-4303 Kaiseraugst, Switzerland

Felix Spindler

Ligands for Pd catalysed cross-coupling reactions A comparison of commercially accessible ligands

KEYWORDS: cross-coupling reaction, palladium, phosphine ligands, Suzuki-Miyaura cross-coupling, Buchwald-Hartwig amination.

In a comparative study, a large variety of commercially available phosphine ligands and types of Pd Abstractcatalysts was evaluated for Suzuki-Miyaura cross-coupling, the Buchwald-Hartwig amination and Buchwald amidation reactions. Electron rich and sterically demanding phosphine ligands such as Buchwald or cataCXium ligands were found to frequently exhibit improved catalyst performance in those cross-coupling reactions compared to generic ligands. In general the use of catalysts of the type PR3-Pd G3 was found advantageous, particularly with respect to low catalyst loadings and high chemoselectivities. Despite the fact, that exceptions from this tendency could be found, as generic diphosphines matched or even outperformed such ligands, it was demonstrated that these modular and in bulk amounts available ligands are a valuable starting point for rapid and efficient development of C-X cross coupling reactions.

INTRODUCTION coupling reactions. While the evaluation of all commercially available ligands is a rather time consuming task, the Over the last two decades the field of Pd catalysed C-C practitioner under time pressure prefers to work with only a and C-X cross coupling reactions has witnessed remark able limited number of potentially active ligands, which are progress, which eventually led to the development of modular, easy to handle (including easily implementable numerous proces ses on pilot plant or production scale (1). catalytic protocols) and readily available. With respect to Such advancement came true because of the availability such restrictions and the fact that no comprehensive of suitable ligands, the broad evaluation of the scope of the systematic comparison of the performance of such ligands methodo logy and the evolution of new ligands and catalyst in cross coupling reactions has been published until today, precursors (2). The dedication of industrial groups to we anticipated that the evaluation of a series of generic implement such procedures on commercial scale was an and advanced ligands for cross coupling reactions might additional driving force for further improvement of the state- be useful as preliminary study that in turn allows for further of-the-art. While a “one-catalyst-fits-all” solution still has to in-depth substrate specific reaction development. In this be identified, the fast and efficient evaluation of the most article, we report a comparison of different types of ligands suited ligand/catalyst system is still a major task in the course being used in selected Pd catalysed C-X coup ling reactions, of process development. From an industrial perspective, such as Suzuki-Miyaura cross-coupling, Buchwald-Hartwig factors such as commercial availability, cost of goods, amination and Buchwald amidation reactions. According to supply assurance and intellectual property associated with the above mentioned criteria for considerable ligands, this ligands and catalysts are equally important as the catalyst study was focused on identifying a limited number of performance. ligands, which are deemed promising for an in-depth optimization of the various cross-coupling reactions and not The evolution of various types of ligands, in particular of the to optimize one catalyst for a specific reaction. Buchwald ligand family is the result of a sophisticated fine tuning of steric and electronic properties of phosphine ligands, which have resulted in the development of very EXPERIMENTAL SETUP OF STUDY effective Pd catalysts for cross-coupling reactions. Nowadays, the practitioner is faced with an overwhelming Totally, 20 different phosphine and diphosphine ligands number of ligands that are considered useful for such cross have been evaluated in this study, which were selected not

26 Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 generic monophosphines

(PPh3, PtBu3, Pcy3, P(2-furyl)3) have been tested in five Pd catalysed cross- coupling reactions (see Scheme 1). As depicted in Scheme 2, two Suzuki-Miyaura coupling reactions (3), two Buchwald- Hartwig amina­tion reactions (4) and a Buchwald amidation reaction (5) were selected for this ligand evaluation study. Scheme 1. Structures of ligands.

The catalysts were generated in situ using either

[Pd(OAc)2], [Pd2(dba)3] or precursor Pd-G3. For four ligands, the in situ formation of the

corresponding PR3- Pd G3 catalysts (see Scheme 3) (6) was monitored by means of 31P-NMR.

In the past, the generation of the catalytically active

“LnPd(0)” species Scheme 2. Cross-coupling reactions. was a critical issue. The Pd precursors

Pd(OAc)2 and Pd2(dba)3 were typically used for such procedures; the drawbacks of this methodology are well documented in the literature (7). Recently, significant progress was achieved in the formation of “L-Pd(0)” species. The introduction of Scheme 3. In situ formation of PR3-Pd G3 catalysts. 2-aminobiphenyl based palladacycles only because of their differences in cone angle, bite angle, with both mono- and diphosphine ligands allows an efficient steric demand and electronic properties, but also because and fast activation of PR3-Pd G3 pre-catalyst, yielding the of their modularity and availability in bulk. Five biphenyl “LnPd(0)” species at room temperature. These pre-catalysts based phosphine ligands (JohnPhos, tBu-XPhos, RuPhos, are easily prepared and can be handled on the benchtop.

BrettPhos and tBu-BrettPhos), which were developed by S. Furthermore, the ratio Pd/ligand (PR3) can be critical with Buchwald and co-workers, cataCXium A, seven ligands of respect to maximum catalyst productivity (turnover numbers). the cataCXium P family (K104-0, K105-0, K106-0, K107-0, Typically 2 eq. PR3 are used in combination with the K108-0, K109-0 and K118-0), dppf, XantPhos, cBRIDP and four precursors Pd(OAc)2 and Pd2(dba)3. In contrast, for maximum

Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 27 catalyst productivity only 1 eq. of the ligand/eq. Pd (plus 2-methyltetrahydrofurane/water and DMF/water, were approx. 20% excess in order to supress catalyst superior in comparison to biphasic anhydrous conditions. deactivation) is required with the palladacycles Pd G3. The best chemoselectivities (up to 80 – 90%) with 2 mol%

However, a standard value of 2 eq. PR3/eq. Pd has been catalyst were obtained with the ligands K118-0, K106-0, tested in this study, which represents the initial part of a K107-0, RuPhos and BrettPhos. process optimization. By taking these results into account, both coupling reactions were reevaluated using 0.5 mol% catalyst, aqueous sol­vents, and both catalyst precursors Pd-G3 and

RESULTS AND DISCUSSION Pd(OAc)2, respectively (Table 1). In both coupling reactions, the precur­ ­sor Pd-G3 outperformed Pd(OAc)2. The evaluation of the various ligands was carried out in a Specifically, using the catalyst K106-0 – Pd G3 in semi-systematic manner using Solvias’ High Throughput­­ combination with aqueous DMF (5.1 vol% H2O) and K3PO4 Experi­men­tation (HTE) platform. In a first series Buchwald at 80°C gave complete conversion to the cross-coupling and cataCXium ligands were tested in all five coupling product 3 after 12 hrs. (86% conv. after 4 hrs.). Basically, reactions applying eight different reaction conditions with 2 the use of Pd(OAc)2 instead of the precursor Pd-G3 mol% catalyst (s/c: 50). In a second experimental series 16 of resulted in lower catalyst activity and/or chemoselectivity.­ the most promi­ ­sing ligands (in­clu­ding commercially The catalyst RuPhos – Pd G3 at s/c 200 had the best available generic ligands) were evaluated systematically overall performance in the coupling­ of 4 with 5 in the under three different reaction condi­ ­tions at 0.5 mol% solvent mixture 2-methyltetrahydrofuran/water (95:5). After catalyst loading. In these series the conversions and yields 4 hrs. the conver­ ­sion was 97% and the yield >99.5%. After were deter­ ­mined after 4 and 12 hrs. reaction time, 12 hrs. complete conversion together with an almost respectively. perfect chemoselectivity was observed for this coupling reaction (yield >99.5%). The same excellent chemoselec­ ­­ tivities were observed with the catalysts K106-0 – Pd G3 and K107-0 – Pd G3, but both were found slightly less active than the RuPhos – Pd G3 catalyst (95% conv. after 12 hrs.). On the other hand, the catalysts K118-0 – Pd G3 and BrettPhos – Pd G3 showed also high activities­ (complete conversion after 12 hrs.), but slightly lower chemoselectivities (96 – 98%). The activity of the catalysts

generated in situ from Pd(OAc)2 and the correspon­ ­ding phos­phine was improved in DMF/water compared to 2-MeTHF/water, as these results revealed.

In both reactions high levels of chemoselectivity (>85%) were observed with basically the same set of ligands. In contrast to literature precedence (9), generic ligands such as triphenylphosphine were less efficient in these two Suzuki-Miyaura coupling reactions compared to the best Buchwald or cataCXium ligands. With many catalysts a fast reaction rate over the initial 4 hrs. was observed,

Table 1. Evaluation of catalysts for Suzuki-Miyaura coupling reactions. which quite often ended up in a stalling of the reaction.

The conversion and the chemoselectivity were determined by HPLC The Buchwald-Hartwig amination reactions 7 + 8 → 9 and (220 nm). Uncorrected integrals were used for the calculation of the 1 + 10 → 11 have been studied in a similar manner as the conversion, the chemoselectivity and the yield. Suzuki-Miyaura coupling reactions. In an initial­ series Reaction Conditions (RC): twelve Buchwald and cataCXium ligands were evaluated A: 1: 50 µmol; 2: 60 µmol; Pd catalyst: 0.5 mol%; PR3/Pd: 2.4; K3PO4: applying eight ‘stan­dard conditions’­ with 2 mol% catalyst 62.5 µmol; DMF/water (95:5): 316 µl; T: 80°C, Time 12 hrs. (4 hrs.) (8). In these eight ‘standard reactions’ the catalysts were B: 4: 50 µmol; 5: 60 µmol; Pd catalyst: 0.5 mol%; PR3/Pd: 2.4; K3PO4: 62.5 µmol; 2-MeTHF/water (95:5): 316 µl; T: 80°C, Time 12 hrs. (4 hrs.) gene­ rated­­ in situ from Pd(OAc)2 (4 experiments), Pd2(dba)3 (2) or precursor Pd-G3 (2). This first series of experiments using the coupling reagents 4-methylaniline Initial attempts to investigate the two Suzuki-Miyaura (8) and aryl chloride 7 re­vealed the catalysts K106-0 – Pd coupling reac­tions revealed the use of aqueous base, i.e. G3 and Pd(OAc)2/RuPhos to have the best overall perfor­ ­ K3PO4, to be favourable in terms of catalyst productivity mance (full conversion and 96% yield after 16 hrs.) in and yields. In the reaction of 4-chloroanisol (1) with 2-methyl-2-butanol. Ligands K101-0 (cataCXium A) and cyclohexenylpinacolatoboron (2) the highest yields of K105-0 performed similarly, but with a slightly lower chemo­ coupling product 3 were achieved in aqueous DMF (10% selec­tivity (94 – 95%).

(v/v) water). By using 2 mol% Pd(OAc)2 in combi­ nation­ with the ligands K106-0, K107-0, K118-0 and RuPhos, the In the Buchwald-Hartwig amination reaction using bicyclic product­ 3 was obtained with 69 – 80% 4-chloroanisol (1) and N-methyl-N-benzylamine (10) the chemoselectivity (T=80°C), respectively. Inte­res­tingly, in catalyst Pd(OAc)2/K108-0 in dioxane was most active and the coupling­ of 4-fluorochlorobenzene (4) with the pinacol selective (100% conversion; 99% yield). Additionally, the boronate 5, again aqueous sol­vents, i.e. same type of catalyst with the ligands JohnPhos and K107-0,

28 Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 Table 3. Evaluation of catalysts for Buchwald amidation reaction.

The conversion and the chemoselectivity were determined by HPLC (220 nm). Uncorrected integrals were used for the calculation of the conversion, the chemoselectivity and the yield.

Reaction Conditions (RC): E: 12: 50 µmol; 13: 60 µmol; §) Pd catalyst: 2 mol%; PR3/Pd: 2.4; NaOtBu ( Cs2CO3): 140 µmol; dioxane (§) 2-Me-2-BuOH): 310 µl; T: 100°C; Time 16 hrs.

performance was obtained independently of the Pd precursor used for the catalyst formation. However, in the amination of 4-chloroanisol (1) with N-methyl-N- Table 2. Evaluation of catalysts for Buchwald-Hartwig amination reactions. benzylamine (10) the performance of these generic ligands was inferior. The conversion and the chemoselectivity were determined by HPLC (220 nm). Uncorrected integrals were used for the calculation of the The amidation reaction using 2-chloropyridine (12) and conversion, the chemoselectivity and the yield. N-phenylurea (13) was studied only with 2 mol% catalyst. The best catalyst for this amidation reaction was Reaction Conditions (RC): Pd(OAc) /BrettPhos furnishing the coupling product 14 C: 7: 50 µmol; 8: 60 µmol; Pd catalyst: 0.5 mol%; PR3/Pd: 2.4, PP/Pd: 1.2; 2 K3PO4: 140 µmol; 2-Me-2-BuOH: 310 µl; T: 100°C, Time 12 hrs. (4 hrs.) with 79% yield. Surprisingly, the use of the in situ generated D: 1: 50 µmol; 10: 60 µmol; Pd catalyst: 0.5 mol%; PR3/Pd: 2.4, PP/Pd: BrettPhos – Pd G3 catalyst resulted in a significant 1.2; NaOtBu: 134 µmol; dioxane: 338 µl; T: 100°C, Time 12 hrs. (4 hrs.) decrease of the yield (70%). K108-0 – Pd G3 and

Pd(OAc)2/K118-0 were identified as alternative, but less chemoselective catalysts generating the coupling furnished the amination product 11 with slightly lower product with 61 – 64% yield. chemoselectivity (92 – 95%). In the second part, the performance of 0.5 mol% catalyst in the two amination reactions was investiga­ ­ted (Table 2). CONCLUSION Surprisingly, in the amination of aryl chloride 7 with 4-methylaniline (8) in 2-methyl-2-butanol (base: NaOtBu) In this comparative study, a large variety of ligands and the catalyst RuPhos – Pd G3 showed the best overall types of Pd catalysts was evaluated for Suzuki-Miyaura performance­ (100% conversion after 4 hrs; 91% yield), cross coupling, Buchwald-Hartwig amination and closely fol­lowed by catalyst dppf – Pd G3 (99% con­ver­sion Buchwald amidation reactions. We experimentally after 4 hrs; 91% yield). XantPhos – Pd G3 and K106-0 – Pd demonstrated that electron rich and sterically demanding G3 afforded the amination product 9 with 99 – 100% phosphine ligands such as Buchwald or cataCXium type conversion and 88% chemoselectivity after 12 hrs. frequently exhibit improved catalyst performance in these Interestingly, the use of Pd(OAc)2 instead of the precursor cross-coupling reactions compared to generic ligands. Pd-G3 resulted only in a marginal decrease of the Specifically, it was interesting to observe that the same chemoselectivity. In the amination of 4-chloroanisol (1) group of ligands, which consisted of BrettPhos, RuPhos, with the sec.-amine 10, the Pd catalysts incorporating the K106-0, K118-0 and K107-0 formed active Pd catalysts for RuPhos ligand showed by far the best performance: full all three reaction types. Exceptions from this tendency conversion and 97% yield after 4 hrs.. Surprisingly, the were also noticed, as generic monophosphines or variation of the Pd precursor (Pd-G3 or Pd(OAc)2) did not diphosphines, such as dppf or XantPhos can match or influence the catalyst performance. Additional promising even outperform such ligands in selected reactions, as the ligands could be K106-0, K107-0 and K118-0, all yielding results of the two Buchwald-Hartwig amination reactions product 11 with significantly lower chemoselectivity­­ (90%). revealed. The best catalysts in this study afforded (almost) The results of this experimental­ series also indicate product complete conversion and high yields (>95%) after 4 hrs., degra­da­tion to occur as an unwanted side-reaction after which indicates that lower catalyst loadings (<0.5mol%) complete conversion.­ Consequently, optimiza­ ­tion of the could be technically feasible. However, it was nicely reaction time might lead to improved chemoselectivity. shown that such structurally more complex ligands are still In contrast to the findings in Suzuki-Miyaura coupling, the crucial for the successful cross-coupling of unactivated, list of the best catalysts (ligands) varied significantly, sterically demanding substrates, opposing the general depending on the type of Buchwald-Hartwig amination trend in achiral cross-couplings where more and more reaction. As can be seen from Table 2, in the amination of ligand free protocols have been developed. In general 7 with 4-methylaniline (8) the generic ligands dppf and the use of catalysts of the type PR3-Pd G3 was found XantPhos were identified as valuable alternatives to the advantageous, particularly with respect to low catalyst best Buchwald and cataCXium ligands. Excellent loadings and high chemoselectivities. Despite the fact

Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 29 that the development of cross coupling reactions is and Suzuki Coupling”, Top. Organomet. Chem. 42, 117 – 124 might ever be empirical (substrate specific), this limited (2012). comparative study nicely demonstrated that it might be 4. a) Lundgren, R.J., Stradiotto, M., “Recent Advances in the Buchwald-Hartwig Amination Reaction Enabled by the possible to narrow the set of considerable ligands down, Application of Sterically Demanding Phosphine Ancillary first by a preselection based on industrial relevant Ligands”, Aldrichimica Acta, 45(3), 59-65, (2012). b) Sperry, parameters, followed by a broad screening in a variety of J. B., Price Wiglesworth, K. E., Edmonds, I., et al., “Kiloscale reactions. Together with the modularity of these ligands Buchwald−Hartwig Amination: Optimized Coupling of Base- (CataCXium P, Buchwald) and rapid screening Sensitive 6-Bromoisoquinoline-1-carbonitrile with (S)-3-Amino- possibilities, we are convinced that a feasible starting 2-methylpropan-1-ol”, Org. Process Res. Dev. 18, 1752 – 1758 point for efficient and fast investigations of cross coupling (2014). reactions was established. 5. a) Yin, J., Buchwald, S. L. ”Pd-Catalyzed Intermolecular Amidation of Aryl Halides: The Discovery that Xantphos Can Be Trans-Chelating in a Palladium Complex”, J. Am. Chem. Soc., 124, 6043 – 6048 (2002). b) Su, M., Buchwald, S. L. “A REFERENCES AND NOTES Bulky Biaryl Phosphine Ligand Allows for Palladium-Catalyzed Amidation of Five-Membered Heterocycles as Electrophiles”, 1. For reviews see: a) de Vries J G, Top. Organomet. Chem. 42, Angew. Chem. Int. Ed., 51(19), 4710 – 4713 (2012). 1 – 34 (2012). b) Magano, J., Dunetz, J.R. ”Large-Scale 6. Bruno, N.C., Tudge, M.T., Buchwald, S.L. “Design and Applications of Transition Metal-Catalyzed Couplings for the preparation of new palladium precatalysts for C-C and C-N Synthesis of Pharmaceuticals”, Chem. Rev. 111, 2177 – 2250 cross-coupling reactions”, Chem. Sci. 4, 916 - 920 (2013). (2011). 7. Li, H.; Seechurn, C. C. C. J.; Colacot, T. J. “Development of 2. Fleckenstein, C.A., Plenio, H. “Sterically demanding Preformed Pd Catalysts for Cross-Coupling Reactions, trialkylphosphines for palladium-catalyzed cross coupling Beyond the 2010 Nobel Prize”, ACS Catal. 2, 1147-1164

reactions – alternatives to PtBu3“, Chem. Soc. Rev. 39(2), 694 (2012) and references therein. – 711 (2010). 8. Lin, Q., Meloni, D., Pan, Y., et al., Org. Lett. 11, 1999 – 2002 3. a) Lennox, A. J. J., Lloyd-Jones, G. C., “Selection of boron (2009). reagents for Suzuki- Miyaura coupling”, Chem. Soc. Rev., 43 9. a) Maiti, D., Brett P. Fors, B.P., et al. “Palladium-catalyzed (1), 412 – 443 (2014). b) Martin, R., Buchwald, S.L. coupling of functionalized primary and secondary amines ”Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling with aryl and heteroaryl halides: two ligands suffice in most Reactions Employing Dialkylbiaryl Phosphine Ligands”, Acc. cases“, Chem. Sci. 2, 57 - 68 (2011). b) Surry D.S., Buchwald, Chem. Res., 41(11), 1461 – 1473 (2008). c) Indolese, A. F. S.L. “Dialkylbiaryl phosphines in Pd-catalyzed amination: a “Pilot Plant Scale Synthesis of an Aryl-Indole: Scale Up of a user’s guide”, Chem. Sci. 2, 27 - 50 (2011). SOC15_NCSS-TeknoScienz_AD2B 7/22/15 2:52 PM Page 1

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Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 31 D.A. SLADKOVSKIY1, N.V. KUZICHKIN1, K.V. SEMIKIN1, P.A. ZERNOV1, D.YU. MURZIN*1,2 *Corresponding author 1. St.Peteresburg State Technological Institute, St.Petersburg, Russia 2. Åbo Akademi University, Turku, Finland

D. Yu. Murzin

Optimal design of catalytic distillation for alkylation of isobutane with 2-butene on a solid catalyst

KEYWORDS: Reactive distillation, alkylation, isobutane, butane, zeolites.

Alkylation of isobutane with butenes is one of the most important processes making high octane number Abstractgasoline. Highly exothermicity requires efficient heat removal. Low temperature implies application of strong (sulphuric and hydrofluoric) acids as catalysts albeit inherent corrosion, pollution and safety problems. The difficulty in applying alternative solid alkylation catalysts is related to deactivation by coking. In order to minimize deactivation an excess of olefin is required. Catalytic distillation, combining reaction and separation, could be proposed to considerably reduce the isobutane recycle and simultaneously to ensure high butenes conversion. Detailed simulations for reactive distillation in a zeolite catalysed alkylation of isobutane with butane were conducted. Various options regarding placement of the reaction section were considered and optimal conditions determined

INTRODUCTION temperature in case of sulphuric acid would result in unwanted increase of viscosity, while an increase of Alkylation of isobutane with butenes can be considered as temperature would lead to formation of tars and sulphur one of the most important processing for obtaining high dioxide. Since HF is not an oxidant somewhat higher octane number gasoline. Alkylate, which is the desired temperature can be used simplifying obviously the cooling product of this process, has a lower vapour pressure and is arrangements, while for the process with sulphuric acid free from presence of sulphur, nitrogen and aromatic cryogenic cooling is needed. compounds. At the moment the share of alkylates in high Influence of pressure on the reaction equilibrium is less octane number gasoline in developed countries approaches straightforward. From the viewpoint of thermodynamics high 13% (1, 2). pressure should be applied influencing in a negative way side reactions, thus in practice mildly elevated pressures (0.2-2 The modern processes for industrial alkylation are based on MPa) are used. utilization of sulphuric and hydrofluoric acids. An excess of A requirement of a low temperature implies that such strong isoparaffin is beneficial from the view of selectivity supressing acids as sulphuric and hydrofluoric acids are used as catalysts side reactions and improving the octane number . Otherwise even if such processes have inherent corrosion, pollution and polymerization of olefins gives undesirable low-octane, high safety problems. boiling point components. The heavier polymerization The traditional alkylation reaction takes place in a medium in products (with more than 10 carbon atoms) known as acid which the hydrocarbon drops are dispersed in a continuous soluble oils tend to deactivate the catalyst. At the same time acid phase. Thus alkylation is often treated as a if the excess is too high it would lead to unnecessary high homogeneous process where the reaction rate is proportional costs for recycling. In industrial conditions typically the mole to the interfacial area. excess of isoparaffin is varied from 6 to 20 depending on the Application of HF results in a higher octane number due to process. The usual I/O ratio ranges from 5 to 8 in sulphuric acid the hydrogen transfer reactions having lower catalyst plants and from 10 to 15 in HF plants. consumption and higher isobutane consumption. Total acidity Alkylation reactions are highly exothermic (on average 75-96 is decreased during operation by contamination with water kJ/mol), therefore heat removal is essential. Low temperature and organics. Contamination with organics more such as 0-10oC with sulphuric acid and ca. 30oC for HF is pronounced in HF process due to higher (order of magnitude preferred being also beneficial by minimizing formation of compared to sulphuric acid) solubility of isobutane. polymerization and cracking by-products. Too low The catalyst activity decreases with time due to dilution,

32 Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 formation of red oil and impurities. Although HF can be This is followed by an exothermal step of electrophillic purified by fractionation to remove water and red oil at the addition to another olefin giving a larger carbenium ion plant site some losses are inevitable as HF forms an azeotrope with water. Contrary to HF complete removal of H2SO4 is (2) needed requiring regeneration by complete decomposition of the acid which is done outside of refineries leading to high overall H2SO4 consumption (100 kg/t of product) compared Subsequent hydride transfer sustains the catalytic cycle to HF losses. resulting primarily in 2,2,3 trimethylpentane

Due to these clear shortcomings there is an apparent interest (3) to apply solid catalysts (1-4). The difficulty in applying solid catalysts in alkylation is related with catalyst deactivation, which is related to coking and subsequent pore blocking Generation of hydrocarbons with a carbon number not preventing access to the active sites. In order to minimize proportional to four, occurs according to the b-scission deactivation an excess (I/O ratio above 7) is required mechanism. Figure 1 displays several potential routes of obviously elevating manufacturing costs for solid-catalyzed b-scission and olefin addition, which are the most probable alkylation. Based on available information two technologies for formation of C5-C8 components. For instance, are close to implementation, namely UOP Alkylene based on carbocations formed because of b-scission in the olefin

AlCl3 (1, 4, 5) and AlkyClean which relies on a zeolitic catalyst addition step will react predominantly with butenes, which (4). UOP Alkylene process uses a riser reactor concept and a concentration is higher compared to other olefins. As a result complex catalyst containing AlCl3 supported on Al2O3 with of b-scission of C9+ at 60-90°С C4+ hydrocarbons are formed promoters, while the AlkyClean process employs several (11,12) while С1-С3 compounds were not detected in butene reactors (6). A demonstration unit of the process had 3 alkylation (9). reactors, where one was used for alkylation, another one was in mild regeneration (mild liquid-phase regeneration using isobutane and hydrogen) and the third one underwent high temperature regeneration.

As an alternative to these technologies a scheme with a catalytic distillation unit could be proposed to considerably reduce the isobutane recycle and simultaneously to ensure high butenes conversion. Such technology (Eurofuel) was developed by Lurgi in co-operation with Südchemie (7) making use of a moving bed reactive distillation, when isobutene and the catalyst enter at the top of the tower, Figure 1. Possible reaction pathways for generation C5-C9 components. while alkene with premixed isobutene is introduced in stages. The catalyst is faujasite based zeolite with a hydrogenation function. Such arrangements are beneficial from the In the current work it was assumed that generation of viewpoint of reaction heat utilization as well as diminishing components С5-С9 occurs according to the overall reactions capital costs. illustrated in Table 1. In addition to these reactions which reflect possible reaction pathways from Figure 1, self- No details on the energy consumption are available, thus the alkylation with formation of n-butane was also considered. present work is aimed at filling this gap by defining an optimal structure of the reactive distillation system and determining an influence of the main parameters on the operational costs

PROCESS SIMULATION

Reaction model A large number of chemical reactions are happening during alkylation, the main being hydride-transfer, olefin addition, isomerisation, b-scission and self-alkylation (3, 8-10).

Since the current work is devoted to a detailed analysis of product separation it was necessary to describe formation of Table 1. Overall equations for production of С4-С9 components. individual components i-C5, C6, C7 and C8. As in other alkylation processes the reaction starts with generation of a carbocation by protonation of the olefin. After than it can Selectivity was calculated in a way that the product abstract a hydride from isobutane forming a tert-butyl composition corresponds to experimental data in laboratory carbenium ion scale experiments for a zeolitic catalyst (4, 9-10,13). The

distribution of isomers С6-С8 provided information about isomerization reactions. Comparison between the calculated (1) and experimental data is given in Table 2.

Monographic special issue: Biocatalysis & Catalysis - Chimica Oggi - Chemistry Today - vol. 33(4) July/August 2015 33 Table 2. Сomparison between experimental and calculated data.

Modelling of catalytic distillation For modelling purposes the systems of equations for the reactor and distillation column were solved separately. Calculations for the complete reactive distillation system were done interactively. The distillation column was described using the MESH approach (material balance, phase-equilibrium, mole balance and energy balance equations). The phase equilibrium constants have a complicated dependence on temperature, pressure and composition (15).

The values of selectivity to various compounds С4-С9+ and stoichiometric coefficients are displayed in Table 3.

Table 3. Parameters of the model for the reaction section.

The separate approach to modelling allowed to use standard calculation methods for the distillation column. Namely the bubble-point method was applied for calculating each tray (16).

The model for the reaction section correspond to a reactor with separation of products:

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