Acetylation of 2-Methoxynaphtalene with Acetic anhidryde over Zr⁴⁺-Zeolite beta

Introduction

Acetylation reaction is mostly done in the chemical industry to synthesize a variety of organic compounds. In many cases the acetylation reaction is not easy to obtain the desired product if there is more than one group in the starting material which can undergo the same reaction. To produce the desired product required special conditions that minimize byproducts. One of the factors that can determine the selectivity of the reaction is the catalyst. Drug class nonsteroidal anti-inflammatory (NSAID) has analgesic effects, antipyretic and anti-inflammatory. Drugs of this class is very effective to reduce the symptomatic pain. From a variety of NSAIDs, each has advantages and disadvantages which looks at the effects of therapeutic and side effects. (S)-Naproxen, or (+)-2-(6-methoxynaphtyl)-propionic acid, is a nonsteroidal anti-inflammatory drug that was introduced under the trade name Synex in 1976. In industry, these compounds were synthesized in four stages, starting with the Friedel-Crafts acylation of 2-methoxyinaphtalene for 2-acetyl-6 methoxyinaphtalene (2,6-ACMN), which is then converted to acid by Willgerodt reaction. Methylation produces a racemic mixture of an acid (R,S) which can be solved efficiently with sinkonidin , to obtain (S)-naproxen (Harrington and Lodewijk , 1997) . This process has several interesting problems. First, Friedel-Crafts acylation is not regiospesifik, and in addition not only 2,6-ACMN formed but also 1,2-ACMN isomer obtaioned, which must be separated by crystallization. Second, a significant amount of aluminum hydroxide and hydrochloric acid waste. Third, a number of undesirable reagents used, such as nitrobenzene as solvent acylation, ammonium sulfide for Willgerodt reaction, sodium hydride and methyl iodide. Furthermore, using of AlCl₃ in stoichiometric amounts. These problems were  combined with the toxicity and trouble some job work procedure, not in accordance with the ongoing process technology (Hoelderich, 1993) . Therefore, studies with alternative procedures which continue to be made more environmentally friendly. Friedel-Crafts acylation reactions are traditionally carried out with reagent AlCl₃/chloride acid, alternative procedure that developed is the use of heterogeneous catalysts with acid anhydride. Some examples of heterogeneous catalysts for the synthesis of fine chemicals and intermediates are functionalised polymers such as zeolites or Amberlist A15 or Nafion (Heinichen and Hoelderich, 1999; Heidekum, Harmer, and Hoelderich, 1998; Heidekum, Harmer, and Hoelderich, 1999). Preparation of Zr⁴⁺-zeolite beta through ion exchange showed that ion exchange increases the surface area, pore volume but lower pore spokes compared the same parameters on the zeolite beta before treatment. Increase in the concentration of Zr⁴⁺ ion exchange in general increase the surface area and pore volume solids , but less pore jejeri show a clear trend . In general, ion exchange porosity results better than impregnation (Cahyono, 2011). Pore ​​size and acidity properties of the resulting catalyst will have a good selectivity for the acetylation of 2-methoxy naphthalene.

The acetylation of 2-MN has been investigated over MCM-41, H-Y, ZSM-12 and BEA, and ZSM-5 and mordenite (Andy et al. 2000), The products are usually obtained, 1,2-ACMN and 2,6-ACMN. Schuster and Holderich (2008) showed that in the aceylation reaction the Fe³⁺– ion-exchanged zeolite beta to a conversion of acetic anhydride of 97%. The selectivity to the desired 2,6-ACMN was 37.4% after 24 h reaction time. A slightly higher selectivity to 2-acyl-6-methoxynaphthalene of 40% at 97% conversion could be achieved in presence of Cu²⁺ ion-exchanged BEA zeolite.  The silver ion-exchanged zeolite gave a selectivity of 53% at 67% conversion. After 350 h reaction time the Cu²⁺ and the Fe³⁺ ion-exchanged zeolite led to complete conversion at a selectivity of 93% while the silver ion-exchanged zeolite deactivated after 48 h reaction time. Cahyono et al. (2010) has been investigated the activity and stereoselectivity of modified zeolite beta on cyclisation-acetylation  of (R)-(+)-citronellal. The affect of catalyst preparing method, temperature, mol ratio of reactant, and solvent on the acetylation of 2-MN with acetic anhydride over Zr⁴⁺-zeolit beta were studied.

Material and Method

Zeolite beta was obtained from Tosoh  (zeolite 940 NHA) with ratio of SiO₂/Al₂O₃ 37. Precursor ZrCl_4­, solvents toluene and dichloromethane, acetic anhydride were provided by EMerck. Characterization of catalysts was conducted by using pyridyn adsorption -IR method at energy laboratory LP2M ITS and morphology of the catalyst by SEM at Physics Laboratory UM. The reaction was performed in a reflux apparatus with cooler and nitrogen gas flow. Product acetylation analysis was done by GC and GC-MS.

Preparation and Characterization of Catalysts

Catalyts was prepared by impregnation method and ion exchange method. Preparation of Zr⁴⁺-zeolite beta(ip) catalyst by impregnation method was adapted from the procedure Yongzhong et al. (2004). At 1.0 g of zeolite beta was added 10 % of Zr⁴⁺ with 0.5 M zirconium chloride and then stirred for 24 hours. After drying at 100 ° C, the samples calcined at 550 ^oC for 3 hours, with a low heating rate of 1 ° C / min. Preparation of catalyst by ion exchange method was done by soaking 1 g of zeolite beta in 25 mL of 0.5 M ZrCl₄ and then stirred for 24 hours, filtered until free of chloride ions. After drying at 100 ° C, the sample calcined at 550 ^oC for 3 h. Acidity of catalysts was determined by pirydin adsorbtion-FTIR method and morphology of catalysts was performed by using scanning electron micrograph (SEM).

In a 3-neck flask equipped with a magnetic stirrer and a cooler was added acetic anhydride (0.95 mL, 10 mmol) ,  0.5 g of catalyst, and 20 mL of toluene and then stirred for 2 min, the mixture was added 1.58 g (10 mmol) of 2-methoxy naphthalene, the mixture heated at 70 ⁰C under N₂ gas flow. During the reaction 1 ml sample was taken after 12 hours, 24 hours and 36 hours. Then added 6 mL of distilled water and 3 ml n-hexane and separated by centrifuge. The organic phase was dried by adding of anhydrous Na₂SO₄, the products were analyzed by GC. The same procedure was done at difference temperature of 140 ^oC. Reactions also repeated with dichloromethane solvent, without solvent, and increasing amount of acetic anhydride.

Results and Discussion

Acidity of Catalysts

Pyridine have been used as probe molecules for the quantitative analysis of surface acidity of modified zeolite beta catalysts by FTIR spectroscopy. A scale of acidity and an evaluation of the relative acid strength were obtained for both Brønsted- and Lewis-acid sites. Table 1 shows the results of acidity analysis by pyridine adsorption-FTIR analysis.

Table 1: Acidity modified zeolite beta with Pyridine adsorption-FTIR analysis

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