Green Catalytic Processes In The Synthesis Of Fine Chemicals

15.2.1 Introduction

Aromatic ketones are valuable intermediate compounds in the synthesis of important fragrances and pharmaceuticals. In many cases, these compounds are currently obtained in homogeneous processes via Friedel-Crafts acylations. However, Friedel-Crafts acylations are real and alarming examples of very widely used acid-catalyzed reactions that are based on 100-year-old chemistry and are extremely wasteful. Replacement of AlCl3 Friedel-Crafts catalysts by solid acids for acylation reactions would drastically reduce the aqueous discharge and solid waste.

In particular, hydroxyacetophenones are useful intermediate compounds for the synthesis of pharmaceuticals. For example, para-hydroxyacetophenone (p-HAP) is used for the synthesis of paracetamol, a well-known antipyretic drug, and ortho-hydroxyacetophenone (o-HAP) is a key intermediate for producing 4-hydroxycou-marin and warfarin, both of which are used as anticoagulant drugs in the therapy of thrombotic disease [1, 2]. In the classical commercial process, p-HAP is obtained via the Fries rearrangement of phenyl acetate in a liquid-phase process involving the use of homogeneous catalysts such as AlCl3, TiCl4, FeCl3, and HF, which pose problems of high toxicity, corrosion, and spent-acid disposal [3]. In an attempt to develop a suitable and environmentally benign process for producing p-HAP, strong solid acids such as ion-exchange resins, zeolites, Nafion, and heteropolyacids have been tested in liquid phase for the Fries rearrangement of phenyl acetate. However, solid acids form significant amounts of phenol together with p-HAP, and these are, in general, rapidly deactivated [4, 5].

Hydroxyacetophenones can also be obtained by the acylation of phenol in liquid or gas phases by employing different acylating agents. In liquid phase, the reaction produces mainly p-HAP using either Friedel-Crafts or solid acid catalysts; but the process is hampered because of environmental constraints and the decay of catalyst activity [6, 7]. In the gas phase, the phenol acylation on solid acids forms predominantly o-HAP, but the reported experimental o-HAP yields are still moderate, particularly because of significant formation of phenyl acetate [8, 9]. An analysis of the literature shows that the potential use of solid acids to obtain hydroxyacetophenones in gas or liquid phases via either phenol acylation or phenyl acetate rearrangement reactions is limited because of relatively low yields and rapid activity decay. The development of more selective and stable catalysts is therefore required to efficiently promote the synthesis of o-HAP. Taking this into account, our research group decided to perform a detailed study of the gas-phase acylation of phenol with acetic acid over different solid acids with the goal of relating the structural properties and the surface acid site density and strength of the solids to their ability to efficiently catalyze the phenol acylation reaction to yield o-HAP. Our studies also focused on the decay of catalyst activity.

TABLE 15.1

Sample Physical Properties and Acidity

TPD of NH3 IR of Pyridine

TABLE 15.1

Sample Physical Properties and Acidity

TPD of NH3 IR of Pyridine

Surface

Area

Pore_diameter

B

L

Catalyst

Sg (m2/g)

dp (A)

Si/Al

|xmol/g

|xmol/m2

(area/g)

(area/g)

HY

660

7.4

2.4

1380

2.1

310

465

HZSM-5

350

5.5

20

770

2.2

337

341

Al-MCM-41

925

30

18

340

0.4

32

135

HPA/MCM-41

SiO2-Al2O3

505

29

352

0.7

560

45

11.3

1005

1.8

68

204

15.2.2 Sample Preparation and Characterization

The o-HAP synthesis was studied on 12-tungstophosfotic acid (HPA) supported on mesoporous MCM-41 silica (sample HPA[30%]/MCM-98; Al-MCM-41 (Si/Al = 18), zeolites HY (UOP-Y54) and HZSM-5 (ZeoCat PZ-2/54), and SiO2-Al2O3 (Ketjen LA-LPV) catalysts. Sample preparation and characterization are detailed in Padro and Apesteguia [10]. Table 15.1 shows the physicochemical characteristics (surface area, pore diameter, chemical composition) and the acidity of the samples. Sample acid properties were probed by temperature-programmed desorption (TPD) of NH3 preadsorbed at 373 K and by infrared (IR) spectroscopy of preadsorbed pyridine. The NH3 surface densities for acid sites in Table 15.1 were obtained by deconvolution and integration of TPD traces (not shown here).

Sample HPA/MCM-41 showed a sharp NH3 desorption peak at about 910 K, which accounts for the strong Bronsted acid sites present on this material. The evolved NH3 from HY, HZSM-5, and SiO2-Al2O3 gave rise to a peak at 483 to 493 K and a broad band between 573 and 773 K. In contrast, Al-MCM-41 did not exhibit the high-temperature NH3 band, showing instead a single asymmetric broad band with a maximum around 482 to 496 K. On an areal basis, zeolites HY and HZM-5 exhibited the highest surface acid density (about 2.2 mmol/m2).

The density and nature of surface acid sites were determined from the IR spectra of adsorbed pyridine. The relative contributions of Lewis and Bronsted acid sites were obtained by deconvolution and integration of pyridine absorption bands appearing at around 1450 and 1540 cm-1, respectively (Table 15.1). In agreement with the results obtained by TPD of NH3, the amount of pyridine adsorbed on Al-MCM-41 after evacuation at 423 K, in particular on Bronsted sites, was clearly lower as compared with acid zeolites or SiO2-Al2O3, reflecting the moderate acidic character of mesoporous Al-MCM-41 samples. The areal peak relationship between Lewis (L) and Bronsted (B) sites on Al-MCM-41 was L/B = 4.2, higher than on SiO2-Al2O3 (L/B = 3). The L/B ratio on HY was 1.5, while zeolite HZSM-5 contained a similar concentration of Bronsted and Lewis acid sites.

15.2.3 Catalytic Results

The gas-phase acylation of phenol (P) with acetic acid (AA) was carried out in a fixed bed, continuous-flow reactor at 553 K and 101.3 kPa. Standard catalytic tests were conducted at a contact time ( W / Fp ) of 146 g h/mol. Main products of phenol acylation with acetic acid were phenyl acetate (PA), o-HAP, and p-HAP; para-acetoxyacetophenone (p-AXAP) was detected in trace amounts. Phenol conversion (XP mol of phenol reacted/mol of phenol fed) was calculated as XP = EYi / (XYi + YP), where EYi is the molar fraction of products formed from phenol, and YP is the outlet molar fraction of phenol. The selectivity to product i (Si, mol of product ¿/mol of phenol reacted) was determined as: Si (%) = (Yi/EYi)100. Product yields (% mol of product ¿/mol of phenol fed) were calculated as ni = Si XP

On all of the samples, o-HAP and PA were the predominant products. At similar phenol conversion levels, the initial o-HAP selectivity was between 67.1% (HZSM-5) and 39.1% (SiO2-Al2O3), while the S0p- HAP values were always lower than 8%. Figure 15.1 shows the evolution of the formation rate of o-HAP as a function of time onstream. By comparing the experimental data in Figure 15.1 at the beginning of the reaction, it is inferred that zeolites HZSM-5 and HY are clearly more active than the HPA/MCM-41 and SiO2-Al2O3 samples for producing o-HAP from phenol, while Al-MCM-41 shows intermediate ro-HAP values.

By determining the effect of contact time on the product distribution, we identified the primary and secondary reaction pathways involved in the synthesis of o-HAP from phenol and acetic acid [10]. Specifically, we proposed (Figure 15.2) that o-HAP is formed from phenol and AA via two parallel pathways:

SB 6 J5

SB 6 J5

Time(min)

FIGURE 15.1 Formation rate of o-HAP as a function of time onstream on: HZSM-5 (■), HY (▼), HPA/MCM-41 (•), SiO2-Al2O3 (O), Al-MCM-41 (▲) (553 K, 101.3 kPa total pressure, W / FP0 = 146 g-h/mol, P/AA = 1, N2/[P + AA] = 45).

Time(min)

FIGURE 15.1 Formation rate of o-HAP as a function of time onstream on: HZSM-5 (■), HY (▼), HPA/MCM-41 (•), SiO2-Al2O3 (O), Al-MCM-41 (▲) (553 K, 101.3 kPa total pressure, W / FP0 = 146 g-h/mol, P/AA = 1, N2/[P + AA] = 45).

Sio2 Al2o3

PA rearrangement

FIGURE 15.2 Synthesis of o-HAP by acylation of phenol with acetic acid.

PA rearrangement

FIGURE 15.2 Synthesis of o-HAP by acylation of phenol with acetic acid.

Direct C-acylation of phenol

O-acylation of phenol forming the PA intermediate, which is consecutively transformed to o-HAP via intramolecular Fries rearrangement or intermolecular phenol/PA C-acylation

The relative rate of the different pathways involved in Figure 15.2 greatly depends on the solid acid employed. In fact, as shown in Figure 15.1, the o-HAP formation rate was higher on acid zeolites containing strong Bronsted and Lewis acid sites (zeolites HY and HZSM-5) as compared with samples containing only Bronsted acid sites (HPA/MCM-41) or exhibiting moderate acidity (SiO2-Al2O3 and Al-MCM-41). This result suggested that both strong Bronsted and Lewis sites are required to produce efficiently o-HAP via both the direct C-acylation of phenol and the acylation of phenyl acetate intermediate formed from O-acylation of phenol.

Figure 15.1 also shows that the o-HAP formation rate does not change with time on HZSM-5, but rapidly decreases on the other samples, particularly on HPA/MCM-41 and HY. Coke formation was determined by analyzing the samples after the catalytic tests by temperature-programmed oxidation. The amount of carbon on the samples ranged from 18.4% C on HY to 2.9% C on ZSM5. The %C formed on Al-MCM-41, SiO2-Al2O3, and HY increased with the sample acidity; i.e., %C was in the order Al-MCM-41 < SiO2-Al2O3 < HY. On the other hand, it was observed that catalyst deac-tivation increased with the amount of carbon on the sample, thereby suggesting that the activity decay for the formation of o-HAP is caused by coke formation. Additional studies were performed to determine the catalyst deactivation mechanism and to ascertain the causes for the superior stability of zeolite HZSM-5 onstream.

Previous work [11] reported that formation of coke via the irreversible polymerization of highly reactive ketene is the main reason of the rapid deactivation observed during the liquid-phase Fries rearrangement of PA on solid acids. Ketenes can be formed via the conversion of PA to P according to Reaction 15.1; these are extremely reactive and unstable compounds that dimerize to diketenes and polymerize very quickly. However, we determined that ketenes are not present during the gas-phase acylation of phenol with AA, because ketenes react rapidly with water formed in reaction (see Figure 15.2) to produce acetic acid [10].

In an attempt to ascertain the nature of the species responsible for coke formation in the synthesis of o-HAP from acylation of P with AA, we studied the conversion of o-HAP with AA on zeolites HY and ZSM-5. The coinjection of o-HAP with AA on HY formed P, PA, and o-acetoxyacetophenone (o-AXAP), and a rapid activity decay was observed. In contrast, HZSM-5 did not produce o-AXAP and did not deactivate during o-HAP/AA conversion reactions. The observed HY deactivation was related therefore with the formation of o-AXAP. Neves et al. [12] reported that coke formed on MFI zeolites during the acylation of phenol with AA is mainly constituted by methylnaphthols, 2-methylchromone, and 4-methylcoumarine. Formation of 2m-cromone and 4m-coumarine can take place from o-HAP and AA via the initial formation of o-AXAP, as depicted in Reaction 15.2:

o-AXAP

2m-Chromone 4m-Coumarine

The assumption that coke is formed essentially via Reaction 15.2 is also consistent with results showing that zeolite HZSM-5, which does not produce o-AXAP when cofeeding o-HAP and AA, does not deactivate. It seems therefore that the superior stability of zeolite HZSM-5 is due to a shape-selectivity effect that avoids formation of the coke precursor species. In other words, zeolite HZSM-5 does not deactivate because its narrow pore-size structure hinders the formation of o-AXAP, which is the key coke precursor in the gas-phase acylation of phenol with acetic acid.

The o-HAP yield on HZSM-5 can be improved by selecting proper reaction conditions. Figure 15.3 shows the evolution of initial o-HAP yield (n0-HAP ) as a function of contact time over zeolites HZSM-5 and HY. The initial o-HAP yield (no- hap ) increases with W/ FP on both z^Hte^ but formation of o-HAP is cleariy favored on HZSM-5 at high W / Fp values. On the other hand, Figure 15.4 plots the evolution of no-HAp as a function of PAA over HZSM-5 and Al-MCM-41 samples. By changing the reactant AA/P ratio from 0.5 to 4, the n°-HAP is increased from 6.0 to 38.6% on HZSM-5. Figure 15.4 also confirms the superior activity of HZSM-5 to produce o-HAP as compared with Al-MCM-41.

Z 10

Z 10

FIGURE 15.3 Initial o-HAP yield as a function of contact time (553 K, 101.3 kPa total pressure, P/AA = 1).

FIGURE 15.4 Initial o-HAP yield as a function of PAA (553 K, 101.3 kPa total pressure, PP = 1.10 kPa, W / F0 = 146 g-h/mol).

In summary, our studies show that zeolite HZSM-5 is an active and stable catalyst for efficiently promoting the synthesis of o-HAP from phenol acylation in the gas phase. Zeolite HZSM-5 contains strong Lewis and Bronsted acid sites and effectively catalyzes the two main reaction pathways leading from phenol to o-HAP, i.e., the direct C-acylation of phenol and the O-acylation of phenol forming the PA intermediate, which is subsequently transformed via intermolecular phenol/PA C-acylation. In addition, on zeolite HZSM-5, the o-hydrox-ycetophenone yield remains stable onstream, and formation of coke is drastically suppressed. The superior stability of zeolite HZSM-5 is due to the fact that the microporous structure of this zeolite avoids the formation of bulky o-acetoxy-acetophenone, which is the key intermediate for coke formation.

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