Ex-ante process design intensification and cost benefits enabled by smart supported chemical and ...

177 Pages·2017·4.12 MB·English

Ex-ante process design intensification and cost benefits
enabled by smart supported chemical and enzymatic catalysis
Citation for published version (APA):
Dencic, I. (2014). Ex-ante process design intensification and cost benefits enabled by smart supported chemical
and enzymatic catalysis. [Phd Thesis 1 (Research TU/e / Graduation TU/e), Chemical Engineering and
Chemistry]. Technische Universiteit Eindhoven. https://doi.org/10.6100/IR770337
DOI:
10.6100/IR770337
Document status and date:
Published: 01/01/2014
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Ex-ante process design intensification and cost benefits enabled
by smart supported chemical and enzymatic catalysis

PROEFSCHRIFT

ter verkrijging van de graad van doctor aan de
Technische Universiteit Eindhoven, op gezag van de
rector magnificus prof.dr.ir. C.J. van Duijn, voor een
commissie aangewezen door het College voor Promoties,
in het openbaar te verdedigen op donderdag
17 april 2014 om 14:00 uur

door

Ivana Denčić

geboren te Pirot, Servië
Dit proefschrift is goedgekeurd door de promotoren en de samenstelling van de
promotiecommissie is als volgt:

voorzitter: prof.dr.ir. J. C. Schouten
1e promotor: prof.dr. V. Hessel
2e promotor: prof.dr. J. Meuldijk
copromotor: dr. M.H.J.M. de Croon
leden: dr. P. Žnidaršič Plazl (University of Ljubljana)
prof.dr.ir. J.A.M. Kuipers
dr. J. Lang (Evonik Industries)
adviseur: dr. C. de Bellefon (University of Lyon)
“If you don’t know how, observe the nature.
It gives clear answers and inspiration.”
(cid:29)ikola Tesla
This work is funded by the EU project POLYCAT: Modern polymer-based catalysts and
micro flow conditions as key elements of innovations in fine chemical synthesis, under
grant agreement No. CP-IP 246095-2 of the European Community's Seventh Framework
Program.

A catalogue record is available from the Eindhoven University of Technology Library
Denčić Ivana
Ex-ante process design intensification and cost benefits enabled by smart supported
chemical and metal catalysts
ISBN: 978-90-386-3578-1

Printed by Gildeprint Drukkerijen
Cover photo www.martin-sand.de
TABLE OF CO(cid:10)TE(cid:10)TS

SUMMARY I
I(cid:9)TRODUCTIO(cid:9) O(cid:9) EX-A(cid:9)TE PROCESS A(cid:9)D COST A(cid:9)ALYSIS 1
1.1. CHEMICAL PROCESS DESIGN AND EX-ANTE PROCESS ANALYSIS 1
1.2. MICROREACTOR TECHNOLOGY AS A PROCESS INTENSIFICATION TOOL 4
1.2.1. Recent patents in micro process technology 4
1.2.2. Multiphase reactions in microreactors 5
1.2.3. Bio-organic syntheses enabled by microreactor technology 7
1.3. PROCESS DRIVEN USE OF MICROREACTORS 8
1.3.1. (cid:29)ovel Process Windows 8
1.3.2. Other process design considerations 10
1.4. THE THESIS OUTLINE 11
REFERENCES 13
PROCESS DESIG(cid:9) A(cid:9)ALYSIS FOR CO(cid:9)TI(cid:9)UOUS-FLOW OPERATIO(cid:9) OF
(cid:9)OBLE METAL VERSUS E(cid:9)ZYME CATALYZED GLUCOSE OXIDATIO(cid:9) 17
2.1. INTRODUCTION 18
2.1.1. Current trends in carbohydrate oxidation 18
2.1.2. Model reaction – selective oxidation of D-glucose 18
2.2. STATE-OF-THE-ART IN GLUCONIC ACID PRODUCTION 20
2.2.1. Identification of the critical aspects of the glucose oxidation process 21
2.2.2. Process intensification criteria 25
2.3. DESIGN OF AN INTENSIFIED REACTOR 25
2.3.1. Falling film microreactor 27
2.3.2. Micro packed bed reactor and comparison with the FFMR performance 31
2.4. ANALYSIS OF THE PRODUCTION COSTS 32
2.5. CONCLUSIONS 36
NOMENCLATURE 36
2.6. APPENDIX 37
REFERENCES 41
GLUCOSE OXIDASE IMMOBILIZATIO(cid:9) O(cid:9) “SMART” (cid:9)A(cid:9)OSPRI(cid:9)G
SUPPORT A(cid:9)D ITS APPLICATIO(cid:9) I(cid:9) E(cid:9)ZYMATIC MICROREACTORS 47
3.1. INTRODUCTION 48
3.1.1. Use of enzymes in microreactors 48
3.1.2. Glucose oxidase 51
3.2. EXPERIMENTAL SECTION 52
3.2.1. Immobilization of glucose oxidase 53
3.2.2. Enzymatic microreactor design 57
3.3. RESULTS AND DISCUSSION 58
3.4. CONCLUSIONS AND OUTLOOK 64
NOMENCLATURE 65
REFERENCES 66
LIPASE BASED BIOCATALYTIC FLOW PROCESS I(cid:9) A PACKED BED
MICROREACTOR 69
4.1. INTRODUCTION 70
4.1.1. Transesterification in a packed bed microreactor – state-of-the-art 71
4.2. EXPERIMENTAL SECTION 72
4.3. KINETICS AND MASS TRANSPORT 73
4.3.1. Slurry reactor model 73
4.3.2. Packed bed microreactor model 76
4.4. RESULTS AND DISCUSSION 77
4.5 CONCLUSIONS 87
NOMENCLATURE 88
4.6. APPENDIX 89
REFERENCES 93
COST A(cid:9)ALYSIS OF PREPARATIO(cid:9) A(cid:9)D USE OF METAL (cid:9)A(cid:9)OPARTICLES
A(cid:9)D IMMOBILIZED E(cid:9)ZYMES AS CATALYSTS I(cid:9) FLOW PROCESSES 97
5.1. INTRODUCTION 98
5.1.1. Application of metal catalysts in micro flow conditions 98
5.1.2. Alternative catalysts and supports 99
5.2. METHODOLOGY FOR CATALYST COST ESTIMATION 102
5.3. CASE STUDIES 103
5.3.1. Metal nanoparticles on HPS support 103
5.3.2. Enzymes supported on a nanospring support 105
5.3.3. Design criteria for catalyst synthesis on a lab scale 107
5.4. RESULTS AND DISCUSSION 108
5.4.1. Case study: Metal nanoparticles on an HPS support 108
5.4.2. Case study: Enzymes immobilized on a nanospring support 112
5.5. CONCLUSIONS AND OUTLOOK 115
NOMENCLATURE 116
5.6. APPENDIX 116
5.6.1. Metal nanoparticles on HPS support - base case 116
5.6.2. Enzymes on nanosprings 119
REFERENCES 120
COST A(cid:9)D PERFORMA(cid:9)CE BE(cid:9)EFIT A(cid:9)ALYSIS FOR I(cid:9)TE(cid:9)SIFIED
PRODUCTIO(cid:9) OF ACTIVE PHARMACEUTICAL I(cid:9)GREDIE(cid:9)TS 123
6.1. INTRODUCTION 124
6.2. PROCESS DESCRIPTION 125
6.3. METHODOLOGY 126
6.3.1. Indicator based analysis 127
6.3.2. Process intensification criteria 129
6.4. RESULTS AND DISCUSSION 130
6.4.1. Reference case 130
6.4.2. Generation of alternatives 133
6.4.3. Scenario analyses 135
6.4.4. Evaluation based on performance metrics 141
6.5. CONCLUSIONS 143
NOMENCLATURE 144
6.6. APPENDIX 146
REFERENCES 148
CO(cid:9)CLUSIO(cid:9)S A(cid:9)D OUTLOOK 153
7.1. CONCLUSIONS 153
7.1.1. Process design concerns 153
7.1.2. Guidelines for catalyst choice 154
7.1.3. The use of micro process technology 155
7.2. OUTLOOK 156
7.2.1. Increasing enzyme productivity 157
7.2.2. A systematic approach for the development of continuous processes towards
pharmaceutical products 158
REFERENCES 160
ACK(cid:9)OWLEDGEME(cid:9)TS 161
LIST OF PUBLICATIO(cid:9)S 163
ABOUT THE AUTHOR 166

Summary

Ex-ante process design intensification and cost benefits enabled by smart supported
chemical and enzymatic catalysis

Selective catalysts, green solvents, miniaturized reactors and continuous flow processing
are considered prime enabling technologies for overcoming drawbacks in conventional
production and achieving chemical process intensification. Process intensification at the
catalyst - reaction - process level leading to economical and environmental benefits is the
aim of this project – transferring the catalyst innovation into a process chemistry and design
innovation. When a novel technology is targeted, an ex-ante cost analysis has an important
role in making decisions on processing. The capital cost of a process is defined once the
process flow diagram and the process scale are known. Further detailed evaluation of
process options and parameter sensitivity for different scenarios leads to an estimation of
the operating costs.
Several reactions have been studied with the objective to define the main cost factors and
the window of economical use of a certain catalyst-reactor pair. A noble metal based
chemical catalyst, polymer supported smart structures and enzyme based catalytic systems
have been explored, combined with either a fixed bed microreactor, a falling film
microreactor or a conventional batch-wise operated stirred tank as their housing.
A methodology for ex-ante evaluation of various operation options included several stages:
• analysis of the reference process,
• identifying bottlenecks and examining their influence on various process levels,
• identifying and ranking the options with respect to process intensification principles,
• experimental validation or real-life tests of applicability of innovations (if available),
• cost analysis and recommendations.
The oxidation of glucose into gluconic acid has been studied as a model reaction to
examine the potential of micro/milli reactor based process, and flow chemistry in general,
concerning gas-liquid-solid reactions with polymeric or inorganic supports. This model
reaction is not initially intended to be applied in microreactors. Instead, this example shows
the methodology to be used when comparison of conventional operation and flow
chemistry needs to be made.
Noble metal- and enzyme-catalyzed micro/milli reactor based processes have been
considered and the cost of the preparations of these catalysts has been analyzed. Noble
metal catalysts prepared by the project partners have been analyzed for their cost
contribution in the oxidation and hydrogenation reactions to produce gluconic acid, sorbitol