Low Toxicity Imidazolium & Pyridinium Ionic Liquids ... Low Toxicity Imidazolium & Pyridinium Ionic

Low Toxicity Imidazolium &

Pyridinium Ionic Liquids:

Synthesis, Antimicrobial Toxicity,

Biodegradation Studies and

Applications in Tsuji-Trost Reactions

By Mukund Ghavre M.Sc.

Under the supervision of Dr. Nick Gathergood

School of Chemical Sciences

Dublin City University

For the award of PhD

September 2012

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Dedicated to Mother…

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Declaration

I hereby certify that this material, which I now submit for assessment on the programme of

study leading to the award of PhD is entirely my own work, and that I have exercised

reasonable care to ensure that the work is original, and does not to the best of my knowledge

breach any law of copyright, and has not been taken from the work of others save and to the

extent that such work has been cited and acknowledged within the text of my work.

Signed: ____________ (Candidate) ID No.: 58112723 Date: _______

Name: Mr. Mukund D. Ghavre

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Abstract

A series of seventy achiral and chiral ionic liquids was designed, synthesized and

characterized. Out of these seventy ILs, fifteen are achiral, twenty one lactic acid based and

rest are mandelic acid based ILs. All compounds were characterized by a number of

techniques including: 1 H,

13 C,

19 F NMR, IR, MS and specific rotation.

Antimicrobial and antifungal toxicity studies were carried out using the representative

examples chosen from these ILs. Lactic and mandelic acid based ILs and ester based achiral

ILs were found to be non toxic towards eight strains of bacteria and twelve strains of fungi.

Antifungal toxicity was performed on two monoester and two diester CILs. Twenty one ILs

were screened for biodegradation studies out of which the ILs with diester functionality were

found to be readily biodegradable.

Six achiral ester and amide based ILs were chosen to employ in Tsuji-Trost reactions as

reaction media. Reactions were performed using two methods consisting use of two different

bases. Chiral catalysts (S,S)-iPr-phosferrox, mandyphos and R-BINAP were used for chiral

induction. Excellent enantioselectivities with moderate yields were obtained in these

reactions.

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Acknowledgements

First and foremost I would like to thank my supervisor Dr. Nick Gathergood for giving me the

opportunity to work in his group and for his support and guidance throughout my PhD.

I’d like to thank all the technical staff for their help, especially Damien, John, Ambrose,

Vincent, Brendan, Catherine, Veronica and Julie (learned a lot from you guys).

I would like to thank Dr. Marcel Spulak for antimicrobial screening (Charles University,

Czech Republic), Dr. Teresa Garcia for biodegradation studies (CSIC, Spain), Sonia Ventura

for antialgal screening (Aveiro, Portugal), Dr. Florence McCarthy for HRMS analysis (UCC,

Cork) and Dr. Brid Quilty for her help in antibacterial screening (DCU).

Also I would like to thank my friends I’ve made over the past four years, especially, Ian

(thank you so much for organic synthesis problem sessions), Monika, Rohit, Jaywant,

Harshad, Shelly, Thomas, Alan & Adam (thank you so much for the help during my thesis

writing), Thu, Debbie, Dan, Andy and Will. I am also very thankful to Martin, Ewa, Wioleta,

Mads and Pavel for their hard-work in LC-MS analysis and antibacterial screening. I’m

grateful for the support from the other friends particularly Rahul, Jitu, Yogesh, Tushar and

Sanjay.

Lastly, I am very grateful to my brother Anand for looking after mother so I could pursue my

PhD.

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Publications List

� N. Gathergood, S. Morrissey, B. Pegot, I. Beadham, M. Gurbisz, M. Ghavre, ‘Ionic Liquid

Solvents’, Eur. Pat. Appl. (2010), EP 2223915 A120100901.

� N. Gathergood, B. Pegot, I. Beadham, M. Gurbisz, M. Ghavre, S. Morrissey, ‘Ionic Liquid

Solvents’, PCT Int. Appl. (2010), WO 2010097412 A1 20100902.

� Ed. A. Kokorin, ‘Ionic Liquids: Applications and Perspectives’, Intech, M. Ghavre, S.

Morrissey, N. Gathergood, ‘Hydrogenation in Ionic Liquids’, 2011, chapter 15, 331-392.

� Ed. H. Xie and N. Gathergood, ‘The Role of Green Chemistry in Biomass Processing and

Conversion’, Wiley. Weilheim. J. Xu, W. Yu, H. Ma, F. Wang, F. Lu, M. Ghavre, N.

Gathergood, ‘Catalytic Conversion of Glycerol’, 2012, Chapter 12, in press.

� S. Ventura, M. Gurbisz, M. Ghavre, F. Ferreira, F. Gonçalves, I. Beadham, B. Quilty, J.

Coutinho, N. Gathergood, ‘Imidazolium and Pyridinium Ionic Liquids from Mandelic Acid

Derivatives: Synthesis and a Bacteria, Fungi and Algae Toxicity Evaluation’, 2012,

submitted.

� N. Ferlin, M. Courty, S. Gatard, M. Spulak, B. Quilty, I. Beadham, M. Ghavre, N.

Gathergood, S. Bouquillon, ‘Biomass derived ionic liquids: synthesis, characterization,

ecotoxicity and use as solvents for catalytic hydrogenation processes’, 2012, Submitted to

ChemSusChem.

� N. Ferlin, M. Courty, A. Hien, M. Spulak, B. Quilty, M. Ghavre, A. Haib, K. Kümmerer,

N. Gathergood, S. Bouquillon, ‘Proline-based ionic liquids as chiral agents in Pd-

catalyzed enantioselective hydrogenation of α,β-unsaturated ketones’, in preparation.

� M. Ghavre, I. Beadham, N. Gathergood, ‘Enantioselective Tsuji-Trost reactions in low

toxicity and readily biodegradable ionic liquids’, in preparation.

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Contents

Project Aim ........................................................................................................................... 1

List of Abbreviations ............................................................................................................. 2

Chapter 1 Introduction to Ionic Liquids ................................................................................. 6

1.1 Need of Green Chemistry ............................................................................................ 7

1.2 Development of Green solvents ................................................................................. 10

1.3 What is an Ionic Liquid ? ........................................................................................... 13

1.4 Brief History of Ionic Liquids .................................................................................... 14

1.5 Synthesis of Ionic Liquids ......................................................................................... 16

1.6 Purification of ILs ..................................................................................................... 19

1.7 Physicochemical and Biological Properties of ILs...................................................... 20

1.8 Applications of ionic liquids in organic synthesis ...................................................... 32

1.9 Introduction to the work in thesis ............................................................................... 50

1.10 References ............................................................................................................... 51

Chapter 2 Synthesis and Characterisation of Ionic Liquids .................................................. 61

2.1 Introduction ............................................................................................................... 62

2.2 Synthesis of Achiral ester and amide based ionic liquids ............................................ 62

2.3 Synthesis of Chiral Lactate and Mandelate based ionic liquids ................................... 71

2.4 Miscellaneous ............................................................................................................ 91

2.5 Summary ................................................................................................................... 95

2.6 Conclusion ................................................................................................................ 96

2.7 References ................................................................................................................. 97

Chapter 3 Toxicity and Biodegradation ............................................................................... 99

3.1 Introduction ............................................................................................................. 100

3.2 Aqueous stability ..................................................................................................... 100

3.3 Toxicity ................................................................................................................... 107

3.4 Antibacterial toxicity of synthesized compounds ..................................................... 113

3.5 Antifungal toxicity of synthesized compounds ......................................................... 118

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3.6 Antibacterial toxicity studies at higher concentration ............................................... 122

3.7 Antialgal Toxicity Studies ....................................