DEGREE PROJECT IN CHEMICAL ENGINEERING AND TECHNOLOGY, FIRST LEVEL STOCKHOLM, SWEDEN 2019 Catalyzed synthesis of aromatic esters Oscar Dalla-Santa KTH ROYAL INSTITUTE OF TECHNOLOGY KTH ENGINEERING SCIENCES IN CHEMISTRY, BIOTECHNOLOGY AND HEALTH DEGREE PROJECT Bachelor of Science in Chemical Engineering and Technology Title: Catalyzed synthesis of aromatic esters Swedish title: Katalyserad syntes av aromatiska estrar Keywords: Catalysis, metallocene, zirconium, zirconocene triflate, aromatic esterification, etherification, bis(cyclopentadienyl)zirconium(IV) bis(trifluoromethanesulfonate), electrophilic aromatic substitution, ester, ether Workplace: KTH, Royal Institute of Technology Department of organic chemistry Supervisor at the workplace: Helena Lundberg Supervisor at KTH: Kaye Stern Student: Oscar Dalla-Santa Date: 2019-07-01 Examiner: Kaye Stern Foreword I would like to thank Helena Lundberg for giving me the opportunity to do this scientific work at the department of organic chemistry at KTH. It has been a great learning experience and amongst the most enjoyable times I have had during my education. I would also like to thank Kaye Stern, my supervisor from the program, for always taking her time and being such a great support. I would also like to thank Giampiero Proietti and Björn Blomkvist for helping me find my way around the laboratory. Abstract In this project the possibilities of using a metallocene catalyst for an aromatic esterification has been studied. The purpose of this scientific work was to study and develop a method with less environmental impact than the conventional for producing aromatic esters, as well as to minimize the use of hazardous chemicals. This method was then to be optimized for synthesizing an aromatic ester. Benzyl alcohol and benzoic acid were used as model substrates throughout this project. They react to form the ester benzyl benzoate, a reaction that is slow. Several metallocene complexes were therefore tried as catalysts for this aromatic esterification. The reaction was also studied in different solvents and under different conditions, such as under inert atmosphere. High performance liquid chromatography (HPLC) was used to sample and study the results of these experiments, with the use of both an internal standard and reference standard. The catalyst that was found to work best for the esterification was zirconocene triflate. The choice of solvent also greatly affects the formation of ester, with hexane found to have the highest positive influence on the yield. We chose to use toluene instead, since it is less toxic and works for a wider variety of substrates than hexane. Using twice the amount of alcohol compared to the acid was also found to be very effective for increasing the yield. The addition of a small amount of water to the mixture under nitrogen gas showed a positive impact on the yield of benzyl benzoate. The esterification did not only form benzyl benzoate as a product but also formed dibenzyl ether and both 2-benzyl toluene and 4-benzyl toluene. These by-products are formed from the benzyl alcohol and they were identified with both 1H-NMR and 13C-NMR, as well as GC-MS. The optimized reaction conditions were to use twice the amount of alcohol in comparison to the acid, with 2 mol% of zirconocene triflate. Half an equivalent of water is also added to the mixture in this method. Toluene is used as solvent and the reaction is conducted at 80℃, resulting in a 74% yield of benzyl benzoate. Sammanfattning Möjligheten att använda en metallocen som katalysator i en aromatisk förestring har undersökts i detta projekt. Syftet med detta vetenskapliga arbete var att studera och utveckla en metod med mindre miljömässig påverkan än de konventionella metoderna för att producera aromatiska estrar, samt för att minimera användandet av farliga kemikalier. Bensylalkohol och bensoesyra har använts som modellsubstrat i detta projekt. De bildar tillsammans estern bensylbensoat genom en långsam reaktion. Flera metallocenkomplex prövades därför som katalysatorer till denna aromatiska förestring. Reaktionen studerades också i olika lösningsmedel och under olika betingelser, såsom under inert atmosfär. HPLC har använts för att ta prover och för att studera resultaten från dessa experiment, med användandet av både intern standard och referensstandard. Den katalysator som fungerade bäst för förestringen var zirkonocentriflat. Valet av lösningsmedel påverkar starkt bildningen av ester, varvid hexan visade sig att ha störst positiv inverkan på utbytet. Vi valde dock att använda toluen, eftersom det är mindre toxiskt och fungerar för fler substrat än hexan. Att använda dubbelt så mycket alkohol som syra, visade sig att vara väldigt effektivt för att få högre utbyte. Att addera en liten mängd vatten till reaktionsblandningen under kvävgas visade en positiv inverkan på utbytet av bensylbensoat. Det bildades inte bara bensylbensoat i förestringen utan även dibensyleter, samt både 2-bensyltoluen och 4-bensyltoluen. Dessa biprodukter bildas från bensylalkoholen och de identifierades med både 1H-NMR and 13C-NMR, samt GC-MS. De optimerade reaktionsbetingelserna är att använda dubbel mängd alkohol i förhållande till syra, med 2 mol% av zirkonocentriflat. I metoden tillsätts även en halv ekvivalent vatten till blandningen. Toluen används som lösningsmedel och reaktionen sker vid 80℃, med ett utbyte av bensylbensoat på 74%. Table of contents List of abbreviations 1 1. Introduction 2 1.1 Purpose 2 1.2 The aim of the project 2 1.3 Methodology 2 2. Theoretical framework 3 2.1 Organic esters 3 2.1.1 The esterification process 3 2.2 Metallocene catalysts 4 2.3 Green chemistry 5 2.4 Reaction Progress Kinetic Analysis 6 3. Results and discussion 7 3.1 Catalysts 7 3.2 Solvents 8 3.3 The effects of an inert atmosphere and water 8 3.4 Reaction kinetics 9 3.4.1 Reaction progress kinetic analysis 9 3.4.2 Kinetics for reactions with added water under nitrogen gas 13 3.5 Optimized reaction 15 3.6 Identifying the by-products of the esterification 16 3.7 Proposed catalytic mechanism 17 4. Conclusion 19 5. Experimental 20 5.1 Standard procedure 20 5.2 Testing different reaction conditions 21 5.2.1 Catalysts 21 5.2.1.1 Synthesizing the fluorinated complexes. 21 5.2.2 Solvents and temperature 22 5.2.3 Reactions under inert and added water 22 5.3 Kinetic studies 23 5.4 Optimization 23 5.5 Large scale reaction without benzoic acid 24 5.5.1 Separation and identification 24 References 25 Appendix 1. Mass spectra 30 Appendix 2. NMR spectra 27 List of abbreviations THF – Tetrahydrofuran zirconocene triflate – bis(cyclopentadienyl)zirconium(IV) bis(trifluoromethanesulfonate) HPLC – High performance liquid chromatography NMR – Nuclear magnetic resonance GC-MS – Gas chromatography-mass spectrometry Internal standard – abbreviated for the 4,4’-di-tert-butyl-biphenyl Cp – Cyclopentadienyl − OTf – triflate or trifluoromethanesulfonate (CF3SO3 ) − PFBS – Perfluorobutanesulfonate (C4F9SO3 ) − PFHS – Perfluorohexanesulfonate (C6F13SO3 ) 1 1. Introduction The focus of this project was to catalytically synthesize an aromatic ester in an environmentally friendly way. The results from this scientific work could, depending on the outcome, be used by Helena Lundberg in further research within environmentally friendly synthesis. Helena works as a researcher at the Division of Organic Chemistry at the Department of Chemistry at KTH, Royal Institute of Technology. 1.1 Purpose The overall purpose of this project was to study and develop a method for environmentally friendly organic synthesis of aromatic esters, in order to minimize the environmental impact of conventional methods as well as to reduce the use of hazardous chemicals. 1.2 The aim of the project This project aimed to develop and optimize a method for synthesizing aromatic esters using an organometallic catalyst. This was done with respect to environmentally friendly organic synthesis. The kinetics for this catalyzed reaction were studied using High Performance Liquid Chromatography (HPLC), with the end-product also being analyzed with Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). 1.3 Methodology The project started with a review of relevant scientific literature about aromatic esterification, metallocene catalysts and green chemistry. After gathering a decent amount of information about these subjects the experimental work begun. The first experiments were about testing different catalysts and then subsequentially moving forward by testing different solvents, temperatures and other conditions for the reaction. After developing an understanding for the reaction and the conditions that favor the catalyzed formation of ester, it was time to identify the products in the reaction mixture. This was done by separating the contents of the reaction mixture and analyzing the different compounds with 1H-NMR, 13C-NMR and GC-MS. The gained spectra were then compared with reference spectra to determine the compounds found. 2 2. Theoretical framework 2.1 Organic esters Esters are a group of organic compounds with the formula R1COOR2, as seen in Figure 1. They are usually derived from a carboxylic acid and an alcohol that has undergone a condensation, with the loss of water. Esters are commonly found in nature in the forms of fats, fatty oils, waxes and fruity fragrances. The ones with lower molecular weight are very volatile and often have pleasant scents. With increasing molecular weight, the volatility decreases and the esters start forming waxes or solids. Esters with longer carbon