Investigation of Biopolymer-based Hydrogels as Green and Heterogeneous Catalysts in CC Bond ...

189 Pages·2014·27.85 MB·English

Investigation
of Biopolymer-based Hydrogels
as Green and Heterogeneous Catalysts
in C-C Bond Formation

Dissertation

Zur Erlangung des Doktorgrades
Dr. rer. nat.
an der Fakultät für Chemie und Pharmazie
der Universität Regensburg

vorgelegt von
Dennis Kühbeck
aus Ortenburg

Regensburg 2014
Die Arbeit wurde angeleitet von: Prof. Dr. David Díaz Díaz

Promotionsgesuch eingereicht am: 17. März 2014

Promotionskolloquium am: 28. April 2014

Gutachter: 1. Gutachter: Prof. Dr. David Díaz Díaz
2. Gutachter: Prof. Dr. Vicente Gotor-Fernández
Der experimentelle Teil der vorliegenden Arbeit wurde in der Zeit von Oktober
2010 bis Oktober 2013 unter der Gesamtleitung von Prof. Dr. David Díaz Díaz am
Lehrstuhl für Organische Chemie der Universität Regensburg angefertigt.
Zusätzliche Betreuerin war von März 2013 bis Mai 2013 Dr. Françoise Quignard
am Institut Charles Gerhardt (ICG) in Montpellier (Frankreich).

Besonders bedanken möchte ich mich bei Herrn Prof. Dr. Díaz Díaz für die
Überlassung des äußerst interessanten Projektes sowie für die hervorragende
Betreuung und Unterstützung.

Meiner Familie

„Die Wissenschaft fängt eigentlich erst da an interessant zu werden, wo sie
aufhört.“

Justus von Liebig

Table of Contents

A Summary 1
B Zusammenfassung 5
C Introduction 9
1. General 9
2. Catalysis 12
2.1 Biopolymer-based Gels 12
2.1.1 Organo- and Biocatalysis 12
2.1.2 Metal Catalysis 16
3. References 21
D Main Part 25
1. Critical Assessment of the Efficiency of Chitosan Biohydrogel Beads 25
as Recyclable and Heterogeneous Organocatalyst for C-C Bond Formation
1.1 Introduction 26
1.2 Results and Discussion 28
1.3 Conclusion 56
1.4 Addendum 57
1.5 Experimental Section 60
1.6 References 70
2. Gelatin and Collagen Proteins-mediated Reactions 75
2.1 C-C Bond Formation Catalyzed by Natural Gelatin and Collagen 75
Proteins
2.1.1 Introduction 76
2.1.2 Results and Discussion 77
2.1.3 Conclusion 84
2.1.4 Experimental Section 85
2.1.5 References 89
2.2 Gelatin Protein-mediated Direct Aldol Reaction 91
2.2.1 Introduction 92
2.2.2 Results and Discussion 93
2.2.3 Conclusion 97
2.2.4 Experimental Section 98
2.2.5 References 101
3. Metal Alginate-catalyzed Nitroaldol (Henry) Reaction 103
3.1 Introduction 104
3.2 Results and Discussion 105
3.3 Conclusion 115
3.4 Addendum 116
3.5 Experimental Section 118
3.6 References 121
4. Investigation of C-C Bond Formation Mediated by Bombyx Mori 125
Silk Fibroin Materials
4.1 Introduction 126
4.2 Results and Discussion 127
4.3 Conclusion 139
4.4 Experimental Section 140
4.5 References 145
5. Evaluation of Polysaccharide-based Materials in the One-pot 149
Deacetylation Knoevenagel Condensation
5.1 Introduction 150
5.2 Results and Discussion 151
5.3 Conclusion 162
5.4 Experimental Section 163
5.5 References 168
E List of Abbreviations 171
F Curriculum Vitae 173
G Acknowledgement 179
A Summary

The present dissertation evaluates the efficacy of different polysaccharides (e.g.
chitosan, alginate and κ-carrageenan) and proteins (e.g. gelatin, collagen, silk
fibroin) as possible catalysts for a variety of C-C bond formation reactions (Figure
1). These biopolymersi can be obtained in different forms (e.g. hydrogels,
mesoporous materials). Among different forms hydrogels are one of the most
interesting since they could act as biphasic and heterogeneous systems in
chemical transformations and facilitate therefore the application as green and
reusable catalysts. Overall, such malleability allows us to investigate the effect of
the morphology and/or physical state of the potential biocatalyst on the reactivity.

2+
2+
2 1∆2(cid:6)& 2+
2 2 2
2 +2
+2 2 +2
1+
(cid:6)
1+∃Φ
Π Θ [
&ΚΛΩΡς∆Θ ∃ΟϑΛΘΛΦ∆ΦΛΓςΡΓΛΞΠς∆ΟΩ
262 1∆
(cid:10)
&+(cid:6)2+ 2
2
2 2
2
2+
2+
]
6ΡΓΛΞΠς∆ΟΩΡΙ (cid:18)&∆ΥΥ∆ϑΗΗΘ∆Θ
Figure 1. Repeating units of used polysaccharides in this work.

This work consists of mainly three parts: Introduction, Main Part (Chapters 1-5)
and Supporting Information enclosed on a CD.
In the firs part of the introduction the importance and the main advantages
of gels when used as reaction vessels and catalysts in organic transformations in
the case of both LMW compound- and (bio)polymer-based hydro-/organogels are
described. The second part of the introduction describes the most important efforts

i The term biopolymer includes both categories of polysaccharides and proteins.
A Summary
during the last decade of polysaccharide-based gels as organocatalysts and
support for catalytic active enzymes or metals.
Chapter 1 describes the results of the evaluation of chitosan-based
materials as organocatalysts in different C-C bond formation reactions, i.e. aldol,
Knoevenagel, nitroaldol (Henry) and Michael addition reaction (Scheme 1). The
chitosan hydrogel and the commercial available powder showed almost similar
activity, but from a practical point of view the recovery of the heterogeneous
system in the case of the hydrogel beads was superior to the powder. The best
results were obtained in the case of the Knoevenagel condensation, followed by
the Henry, Michael addition and aldol reaction. Most importantly, a strong
correlation between the pH of the hydrogel and the reaction outcome could be
observed. Therefore, a meticulous washing of the prepared hydrogel was essential
before the material was submitted as organocatalyst to the above mentioned
reactions.

22 &&11
33ΚΚ
55(cid:16)(cid:16) ++ &&11
&&11
22
55(cid:6)(cid:6) 55(cid:6)(cid:6) 55(cid:17)(cid:17)&&++(cid:6)(cid:6)1122(cid:6)(cid:6)
55(cid:10)(cid:10) ++22 22++
++∴∴ΓΓΥΥΡΡϑϑΗΗΟΟςς 33ΡΡΖΖΓΓΗΗΥΥ
%%ΛΛΡΡΣΣΡΡΟΟ∴∴ΠΠΗΗΥΥ(cid:18)(cid:18)ΕΕ∆∆ςςΗΗΓΓ
00∆∆ΩΩΗΗΥΥΛΛ∆∆ΟΟςς
∃∃ΗΗΥΥΡΡϑϑΗΗΟΟςς ))ΥΥΗΗΗΗ]]ΗΗ(cid:30)(cid:30)ΓΓΥΥΛΛΗΗΓΓ00∆∆ΩΩΗΗΥΥΛΛ∆∆ΟΟςς
++22 22 11++
22 22++ 22++ (cid:6)(cid:6)
55(cid:10)(cid:10)
55(cid:6)(cid:6) 55(cid:16)(cid:16) 55(cid:16)(cid:16) 55(cid:16)(cid:16) 1122(cid:6)(cid:6)
&&11
&&11
55(cid:6)(cid:6) 55(cid:17)(cid:17)
33ΚΚ
Scheme 1. Overview of tested C-C bond formation reactions.

Chapter 2 summarizes the results obtained by gelatin- and collagen-based
materials-mediated nitroaldol (Henry) and direct aldol reaction. Under
physiological temperature in DMSO the powdered form of both proteins showed
2