chemical and process-design intensification in flow - seen

Volker Hessel [email protected]

Eindhoven University of Technology

Department of Chemical Engineering and Chemistry

Micro Flow Chemistry and Process Technology

CPAC / ATOCHEMIS Rome Workshop –Rome 25-27 March 2013

Chemical and Process-Design Intensification in Flow - Seen Holistically

Holistic Process Papers’ “The whole is more than

the sum of its parts"

Aristotle (Αριστοτέλης)

“DA VINCI IS GREEN … 1st GPS EDITORIAL 2012

FULL-CHAIN, HOLISTIC VIEWPOINT

Holistic Route Selection

DOW paper; Leng et al. OPRD (2012)

dx.doi.org/10.1021/op200264t

http://en.wikiquote.org/wiki/File:Aristotle_Altemps_Inv8575.jpg

HOLISTIC IDEAS NEED SYNERGY

– RESEARCHER CLUSTERING

MULTIPLE-ORIFICE RE-DISPERSION

MICROREACTOR AS SOLUTION

● Adapted orifice spacing

● RT = 23 °C

● vRkt = 0.34 ms-1

Illg, T. et al. (2012) Green Chem., 14, 1420 - 1433

C

0.0 0.2 0.4 0.6 0.80

20

40

60

80

100

Co

nvers

ion

an

d y

ield

/ %

Reactor length / m

Conversion tert.-butylhydroperoxide

Conversion pivaloylchloride

Yield tert.-butyl peroxypivalate

T. Illg, V. Hessel et al. Green Chem. 14 (2012) 1420-1433.

T. Illg, V. Hessel et al. ChemSusChem 4, 3 (2011) 392-398.

T. Illg, V. Hessel et al. Chem. Eng. J. 167, 2-3 (2011) 504-509.

CH3 O

CH3

CH3

O-

K+

+CH3

CH3

CH3

O

Cl

CH3

CH3

CH3

O

O

O

CH3

CH3

CH3

-KCl

Multiphase dispersion

THERMAL IMAGING UNDER

REACTIVE CONDITIONS

0 30 60 90 120 150 18020

40

60

80

100Dosing point 2

TBPP formationDosing point 1

KTBP formation

Tem

pera

ture

/ °

C

Reactor length / mm

0 30 60 90 120 150 180

20

40

60

80

100

40 mLmin-1

9 Lmin-1

21 mLmin-1

0 mLmin-1

0

20

40

60

80

100

90004021

Co

nvers

ion

an

d y

ield

/ %

Utility fluid flow rate / mLmin-1

Conversion tert.-butylhydroperoxide

Conversion pivaloylchloride

Yield tert.-butyl peroxypivalate

0

Experimental:

● vRkt = 0.6 ms-1

● t = 2 s

● QUtility = 0, 21, 40, 9000 mLmin-1

• Shortened t

• Increased yield

• Optimum RT at about 40°C

Multiphase dispersion

[1] Azzawi et al. Method for the production of organic peroxide by means

of micro reaction technique, US20090043122, 2009

● 9 Orifices

● 10x52 cm Loops

● RT: 40°C

● YTBPP: 78%

● t: 15 s

● STY: 55600 g/Lh

Micro reactor process [1]

● RT: 10 - 20°C

● YTBPP: 93 % bei ~6 min

● STY: 3600 g/Lh (-10 - 20°C)

3 x 350 L Cascaded batch [1]

● RT: 10 - 20 °C

● YTBPP: 84% bei ~100 min

● STY: 190 g/Lh (8 - 20°C)

● 9 Orifices

● 10x5 cm Loops

● RT: 40°C

● YTBPP: 64%

● t: 1.5 s

● STY: 469000 g/Lh

Reactor length Temperature control Combination

Optimum design

BENCHMARKING FOR

PRODUCTIVITY

Definition of Process Window

p

T

Limitations in T

Limitations in p

Process

window

• The microreactor instrumentation has widened process windows

• Question is still: can we make them bigger?

T

Stouten et al. Aust. J. Chem. 66 (2013) 121

Hessel et al. ChemSusChem(2013) onlineHessel et al. Chem. Eng. Sci. 66 (2011) 1426Illg et al. Bioorg. Medic. Chem.18 (2010)3627

Hessel Chem. Eng. Technol. 32 (2009)1655Hessel et al. Energy Environ. Sci. 1 (2008)467

Hessel Curr. Org. Chem. 9 (2005)765

NOVEL PROCESS WINDOWS

2nd and 3rd INTENSIFICATION FIELDS

Pressurized high-T

capillaries

Propel

Coflore

Flowsyn

X-Cube Flash Asia 320

R Series

COMMERCIAL FLOW CHEMISTRY EQUIPMENT FOR HARSH CONDITIONS

HUISGEN CYCLOADDITION–

TEMPERATURE INFLUENCE

0

10

20

30

40

50

60

70

80

90

100

140 160 180 200

69 % 74 %

91 % 78 %

H N

MR

Yie

ld [

%]

Temperature [ºC]

Reaction Conditions

Flow Rate 10μL/min

ζ (min) 10

Solvent NMP

Cu(CH4CN)4BF4 2.50 mol%

Alkyne M 0.23

Azide M 0.23

A. Carlos-Varaz, V. Hessel, T. Noel, Q. Wang ChemSusChem 5, 9 (2012) 1703-1707.

High-T

HANTZSCH DIPYRIDINE SYNTHESIS

- TEMPERATURE INFLUENCE

Diverse syntheses made in flow in a few min; 50 – 70% yield

High-T

FLASH-FLOW PYROLYSIS

D. Cantillo, H. Sheibani, C. O. Kappe

J. Org. Chem. 77 (2012) 2463-2473.

• Flash vacuum pyrolysis (FVP)

- 400−1100°C; high vacuum

• Flash flow pyrolysis (FFP)

- 160−350°C, 90−180 bar

High-T

Solvent

CLAISEN REARRANGEMENT

- SOLVENT

0

10

20

30

40

50

60

70

80

90

100

220 240 260 280 300

Yie

ld [%

]

Temperature [˚C]

High-T

T. Noel, V. Hessel et al. Tetrahedron 69, 14 (2013) 2885-2890.

High-c


- CONCENTRATION


High-T

JOHNSON-CLAISEN REARRANGEMENT

- TEMPERATURE

0

20

40

60

80

100

120 140 160 180 200 220 240

Yie

ld [%

]

Temperature [℃]

O

OOH

+O

O

O

O

OO

AcOH


S. Borukhova, A. Carlos Varas, V.

Hessel, Q. Wang, P. Watts, C. Wiles,

Poster at IMRET12 (2011).

K.A. Swiss, R.A. Firestone, J. Phys.

Chem. A 104 (2000) 3057-3063.

Labtrix 25 bar Home-built 400 bar TU Darmstadt

2000 bar

High-p

PRESSURE IMPACT FOR

1,3 DIPOLAR CYCLOADDITIONS

45

50

55

60

65

70

50 100 150 200 250 300

Co

nvers

ion

(%

)

Pressure (bar)

High-p


- PRESSURE


1,2,3-triazole

Prevents Seizures & Lennox–Gastaut syndrome

Proposed route

RUFINAMIDE – TOP-200 BLOCKBUSTER

FIRST RESULTS

- 1,3 DIPOLAR HUISGEN CLICK CHEMISTRY

0.7

0.8

0.9

1

0 20 40 60 80

Co

nvers

ion

[%

]

p [bar]

Huisgen Cycloaddition

Res. Time= 3 min

Flow rate=327 µl/min

Cu-R<1 mol%

T=90 ̊ C

Nucleophilic Substitution

High-p

HIGH-p BATCH RESULTS FOR

RUFINAMIDE FLOW SYNTHESIS

Activity with pressure

Activation volume

High-p

S. Borukhova, V. Hessel, T. Noel, Q. Wang

et al. Green Chem. (2013) to be submitted

M. Busch

1H-NMR FOR REGIOISOMER DETECTION

S. Borukhova, T. Noël , V. Hessel, et al. Green Chem. (2013) to be submitted.

S.C. Stouten, Q. Wang, T. Noël, V. Hessel,Tetrahedron Letters (2013) in press/online

SUPPORTED AQUEOUS

PHASE CATALYST (SAPC)

Base Yield

Et3N 83%

DBU 90%

DABCO 90%

DMAP 19%

pyridine 0%

Base variation

Batch

SAPC – BATCH vs FLOW

PROCESS CHEMISTRY ITEMS

Batch Flow

Product/catalyst separation? Yes Yes

Direct reuse of catalyst? No Yes

Catalyst use per runa 0.4 mol%

(11 mg) 0.01 mol% (0.27 mg)

Catalyst use for a 20 run sequence

0.06 mol%b

<0.001 mol%c

Yield and Reaction time 83% 4 h

21% 2.9 min

S.C. Stouten, Q. Wang, T. Noël, V. Hessel,Tetrahedron Letters (2013) in press/online

10 x [Catalyst]

Soybean Oil Epoxidation –

“NPW in Real World”

B. Cortese, M.H.J.M. de Croon, V. Hessel Ind. Eng. Chem. Res. 51 (2012) 1680-1689.

Oxir

an

e n

um

ber

Time [min]

Oxir

an

e n

um

ber

Time [min]

Simulated

Co

nvers

ion

[%

]

Temperature [C]

Exper.

Dream

Reality

>7

<4

Epoxidation – Pilot Plant

© 03.06.2013

Less harsh conditions were used, and a continuous, faster and able

to work at higher temperature set-up was built at Microinnova.

NPW achieved (after some fight against real world)

1. High-T, large interface

2. Medium-T, medium interface

100 C 70-90 C

0.1

1

10

0.1 1 10

Dif

fusio

n c

oeff

icie

nt

(*10

9)

Viscosity

Anionic Polymerization

– Physically Fully Segregated System = Ideal!

© 03.06.2013

Diffusivity Viscosity

ABD

,

1

ssp

s

s sp

or

2

sp c k c

MW 0.01

0.1

1

10 100 1000

[]

MW [kg/mol]

Viscosity

Dif

fusio

n

co

eff

icie

nt

[x10

9]

MW [kg/mol]

[]

Velocity

Diffusivity

Bringing the NPW to Industrial Production

© 03.06.2013

NPW industrially

achieved

A new continuous, fast

safe process

PDI (flow): 1.04

Residence time [s]

Mo

lecu

lar

weig

ht

Experiment

Simulation

„VERBUND“ INTEGRATION STRATEGY

IN THE SCHELDE DELTA, ANTWERP/B

• Piping interconnection

• Short transportation paths

• Energy integration

• Valued-added chemicals’ chain:

Methionin/Evonik

Reaction Network – Multi-step in Flow

Process integration

TELESCOPED MULTI-STEP SYNTHESIS

Aqueous

Phase

Organic

Phase

EDTA (aq)

NMP

Cu

* The European Agency for Evaluation of

Medicinal Products, London, UK, 2002.

Almost complete phase separation

EtOAc

Triazole

Cu?? Syrris, Flexx

module

15 ppm in API is allowed.

A. Carlos-Varaz, V. Hessel, T. Noel, Q. Wang

ChemSusChem 5, 9 (2012) 1703-1707.

3-STAGED Cu SEPARATION IN FLOW

Extraction Stage Residual Copper

start 3156 ppm

1 159 ± 9 ppm

2 97 ± 3 ppm

3 14 ± 1 ppm

Process integration

• EMMA is cheaper + less toxic dipolarophile as

• Not as active under diluted conditions

• Solvent free synthesis results in >80% yield

given 10 min res. time at 200˚C and 70 bar

• Diluents

NMP – 1:6

ACN- 1:10

MeOH- 1:14

• With CAN: 2 g/h at 200˚C and 60 bar

Ease of

purification

S. Borukhova, T. Noël , V. Hessel, et al.

Green Chem. (2013) to be submitted

Process integration

1st STEP: SOLVENT-FREE CYCLOADDITION

AND FURTHER OPTIMZATION

EMMA (methyl trans 3-

methoxy acrylate)

Cyclohexane

KA Oil

Cyclohexene

Adipic Acid

ADIPIC ACID

- DIFFERENT ROUTES

Flow process design

needs reaction design

V. Hessel, I. Vural Gursel, Q. Wang, T. Noel, J. Lang, Chem. Eng. Tech. 35 (2012) 1184

V. Hessel, I. Vural Gursel, Q. Wang, T. Noel, J. Lang, Chem. Ing. Tech. 84 (2012) 660

I. Vural Gursel, V. Hessel, Q. Wang, T. Noel, J. Lang, Green Proc. Synt. 4 (2012) 315

Process integration

Organic phase

Aqueous phase

Syringe pump

Syringe pump

Products

Glass

window

Oil Bath

Thermo-couple

InletOutlet

Inlet

Outlet

T-mixer

90 C, 20 min

n(H2O2): n(cyclohexene):

n(Na2WO4): n(PTC) =

440:100:6.6:1

ADIPIC ACID

- FUNCTION OF OXIDISING STRENGTH

M. Shang, T. Noël, Q. Wang, V. Hessel,

Chem. Eng. Technol. (2013) accepted

H2SO4

90 C, 20 min


n(Na2WO4): n(PTC) =

440:100:6:6

ADIPIC ACID

– FUNCTION OF MINERAL ACID

HOOCCOOH

adipic acid

oxidation

Ohydrolysis

H2O

OH

OH

oxidation OH

O

oxidationO

O

OH

oxidationO

O

O

hydrolysis

H2O

M. Shang, T. Noël, Q. Wang, V. Hessel,

Chem. Eng. Technol. (2013) accepted

0

32.9

42

49.5

42.5

31

0

10

20

30

40

50

60

60 70 80 90 100 110 120

Temperature (℃)

Yie

ld

of

ad

ipic

acid

(%

)

Oxidising agent, solvent,

Co-catalyst, PT catalyst,


n(Na2WO4): n(PTC)=440:100:6:6

50% H2O2, c(H+) = 1.27mol/l

ADIPIC ACID - PROCESS CONDITIONS

FOR BEST CURRENT YIELD

M. Shang, T. Noël, Q. Wang, V. Hessel, Chem. Eng. Technol. (2013) accepted

90 C, 20 min

n(H2O2): n(cyclohexene)=440:100

50% H2O2 , c(H+) = 0.63 mol/l

ADIPIC ACID - PROCESS CONDITIONS

FOR BEST CURRENT YIELD

PTC

Na2WO4

PTC +

Na2WO4

M. Shang, T. Noël, Q. Wang, V. Hessel, Chem. Eng. Technol. (2013) accepted

ADIPIC ACID – ANALYTICAL

PURITY DETERMINATION

1H NMR

13C NMR

6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 14.5 15.0 15.5 16.0 min

-25

0

25

50

75

100

125

mVRI

HPLC

PROCESS DESIGN OF THE TRADITIONAL

TWO-STEP & NEW ONE-STEP PROCESS

Process integration ‘2-Step’

‘Direct’

I. Vural Gursel, Q. Wang, T. Noel, V. Hessel, Chem. Eng. Trans. 29 (2012) 565

COST ANALYSIS – ADIPIC ACID P

urc

ha

se

Co

st o

f E

qu

ipm

en

t, M

€

0

5

10

15

20

25

30

35

40

45

2-Step Route Direct Route

Pumps

Compressors

Dryer

Vessels / tanks

Distillation columns

Centrifuges / Filters

Crystallizers

Reactors

Cost Analysis – Adipic Acid

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2-Step Route Direct Route

Pumps

Compressors

Dryer

Vessels / tanks

Distillation columns

Centrifuges / Filters

Crystallizers

Reactors

I. Vural Gursel, Q. Wang, T. Noel, V. Hessel, Chem. Eng. Trans. 29 (2012) 565

To

tal P

urc

ha

se

Co

st

of

Eq

uip

me

nt

(Sh

are

of

Co

sts

)

Other

Equip.

Other

Equip.

Reactor

Reactor

Energy Consumption Analysis

Direct Route

Total

Equipment Energy

Consumption, MW

Equipment Energy

Consumption, MW

Reactors Q -119.0 Heat Exchangers Q 28.3

Concentrating Still Qc -93.0 Q 35.0

Crystallizers Q -27.0 Q -2.5

Q -30.0 Dryer Q 4.7

Energy 2-Step Route Direct Route

Power Requirement, MW 4.4 0

Heating Requirement, MW 295.9 68.0

Cooling Requirement, MW 380.6 271.5

Total, MW 680.9 339.5

I. Vural Gursel, Q. Wang, T. Noel, V. Hessel, Ind. Eng. Chem. Res. (2013) submitted

HEAT INTEGRATION – PINCH ANALYSIS

Direct Route


HEAT INTEGRATION WITH CONVENTIONAL

AND COMPACT HEAT EXCHANGERS


ΔTmin = 10°C ΔTmin = 1°C

Shell-and-tube heat exchanger Micro-/millichannel heat exchanger

Payback time:

7 months (X=50%) Vural Gursel, Chem. Eng.

Trans. 35 (2013) submitted

DIRECT ROUTE – LCA FOOTPRINT

1. AP: acidification potential (average European)

2. GWP 20a: climate change in 20 years

3. EP: Eutrophication potential (average European)

4. FAETP 20a: freshwater aquatic ecotoxicity in 20 years

5. HTP 20a: human toxicity in 20 years

6. Land Use

7. Malodours Air

8. MAETP 20a: marine aquatic ecotoxicity in 20 years

9. High NOx Photochemical oxidant creation potential

10. Depletion of abiotic resources

11. TAETP 20a: Terrestrial ecotoxicity in 20 years Database: Ecoinvent. Source: CML2001

Q. Wang, I. Vural Gursel, M.

Shang, V. Hessel, Energy

Environm. Sci. (2013) submitted

TWO-STEP ROUTE – LCA FOOTPRINT

1. AP: acidification potential (average European)

2. GWP 20a: climate change in 20 years

3. EP: Eutrophication potential (average European)

4. FAETP 20a: freshwater aquatic ecotoxicity in 20 years

5. HTP 20a: human toxicity in 20 years

6. Land Use

7. Malodours Air

8. MAETP 20a: marine aquatic ecotoxicity in 20 years

9. High NOx Photochemical oxidant creation potential

10. Depletion of abiotic resources

11. TAETP 20a: Terrestrial ecotoxicity in 20 years Database: Ecoinvent. Source: CML2001

Q. Wang, I. Vural Gursel, M.

Shang, V. Hessel, Energy

Environm. Sci. (2013) submitted

GLOBAL WARMING POTENTIAL – FOR BOTH

ROUTES AND HYPOTHETICAL SCENARIOS

Q. Wang, I. Vural Gursel, M. Shang, V. Hessel, Energy Environm. Sci. (2013) submitted

HOLISTIC LIFE-CYCLE ASSESSMENT –

REACTION-RELATED GREEN METRICS

Atom Efficiency E-Factor

Q. Wang, I. Vural Gursel, M. Shang, V. Hessel, Energy Environm. Sci. (2013) submitted

Impact category DR

X* = 4.6% DR

X = 40% DR

X = 50% DR

X = 98% CTR

X = 4.6% AP (×10-3 kg SO2) 18.7 13.8 13.8 13.9 48.8

Malodours Air (×104 m3 Air) 16.2 6.7 6.6 6.3 7.0 POCP (×10-3 kg ethylene) 2.7 1.8 1.8 1.8 10.1

EP (×10-3 kg NOx) 11.0 7.5 7.5 7.4 94.7 FAETP 20a (kg 1,4-DCB) 1.9 1.5 1.5 1.3 1.0 MAETP 20a (kg 1,4-DCB) 1.2 0.9 0.9 0.8 0.6

Depletion of abiotic resources (×10-3 kg antimony)

83.7 53.2 53.0 51.0 46.7

TAETP 20a (×10-3 kg 1,4-DCB)

0.3 0.2 0.2 0.2 0.2

Land Use (×10-3 m2) 73.0 58.4 58.9 55.4 41.4 HTP 8.7 7.7 7.8 8.6 5.6

GWP 20a 11.0 6.3 6.3 5.9 6.7

LCA

-Amino alcohols /

Threonine Aldolase

Transesterification /

Lipase (Antarctica)

Gluconic acid /

Glucose Oxidase

REACTIONS INVESTIGATED IN

ENZYMATIC MICROREACTORS

Silicon Dioxide Nanosprings

100 % accessible surface

area (350 m2/g)

Low resistance to fluid flow

Mixed matrix membrane

Absence of mass transfer

limitations

Energy efficiency for

separation

Convenient scale-up

Eupergit

High density of oxirane

groups, operational

stability

Industrial application

SUPPORTS FOR ENZYMATIC

MICROREACTORS

Indirect method

IMMOBILIZATION PROCEDURES

Direct method

Nanosprings

Eupergit

GPTMS method

H. Fu, I. Dencic, V. Hessel et al. Chem. Eng. J. 207-208 (2012) 564-576

-AMINOALCOHOL DIASTEREOMERS

AND ENANTIOMERS

J. Tibhe, T. Noel, Q. Wang, V. Hessel et al.

Chem. Eng. J. (2013) to be submitted

Analytical HPLC

with chiral column, Chirex

3126 (D)-penicillamine column

Enzyme immobilization efficiency

Optimization with incubation time

REACTION RESULTS WITH

THREONINE ALDOLASE

Batch

Stirred

Flow

Immobilized enzyme

Flow

Free enzyme in slug flow

J. Tibhe, T. Noel, Q. Wang,

V. Hessel et al. Chem. Eng. J.

(2013) to be submitted

327 €/genzyme

7321 €/genzyme

225 €/genzyme

I. Dencic, V. Hessel, M.H.J.M. de Croon, J. Meuldijk, C.W.J.

van der Doelen, K. Koch ChemSusChem 5 (2012) 232-245

I. Dencic, J. Meuldijk, M.H.J.M. de Croon, V. Hessel J. Flow Chem. 1, 1 (2011) 13-23

COSTS ENZYME IMMOBILIZATION

Enzyme process cost

value of target product important (gluconic acid – bulk, amino alcohols – high value),

immobilization procedure influences costs, (but also activity)

process optimization to be done.

* Performed at GoNano Technology

Enzyme used β Galactosidase Glucose oxidase Threonine aldolase

Target product galactose* gluconic acid Phenyl ethanolamine

(in 2-step synthesis)

Enzyme immobilized, mg 15 16 2.6

Catalyst cost (€) 17.8 3.6 11.7

Product price (€/g) 0.7 0.3 8.4

Catalyst cost per one run,

€/gprod

2201 37.5 3903

Number of reuses needed 31446 1249 4647

I. Dencic, J. Meuldijk, M.H.J.M. de Croon, V. Hessel J. Flow Chem. 1, 1 (2011) 13-23

Enzyme deactivation

Pressure drop

Target production for pharmaceuticals = 1 – 10 g/h

Mass transfer limitations

Costs

Reactor[a]

Enzyme Support

(mg)

Amount of immobilized

enzyme (mg)

Amount of active

enzyme (mg)

Productivity

(g/h)[b]

GoNano v1 GOx 11.5 7.1 0.71 0.099

GoNano v2 GOx 100 87 6.17 0.397

GoNano v1 TA 17.5 3.51 0.45 0.212

GoNano v2 TA 100 20.1 2.59 1.210

Eupergit TA 133 1.15 0.60 0.280

Membrane TA 750[c]

0.88 0.088[d]

0.041

THEORETICAL POTENTIAL OF PRODUCTIVITY

OF ENZYMATIC MICROREACTORS

H. Fu, I. Dencic, V. Hessel et al. Chem. Eng. J. 207-208 (2012) 564-576.

Amount of enzymes: Flow: 146 g L-1 vs. Batch: 2.4 g L-1

0

0.2

0.4

0.6

0.8

1

0 10 20 30 40 50 60 70 80 90 100

Co

nvers

ion

(-)

Time (min)

(■) Flow reactor; molar ratio: 1 : 2

(▲) Batch reactor; molar ratio: 1 : 5

Productivity: 1.9 g/l 2.86 ml/h; 5 mol/l

FLOW vs. BATCH – LIPASE-NOVOZYM 435

ENZYMATIC MICROREACTOR

I. Dencic, S. van Veen, M. de Croon, J. Meuldijk, V. Hessel et al. Ind. Eng. Res. Dev. (2012) to be submitted

CONTAINER PLANT FOR COPIRIDE

– AR EVONIK SITE HANAU

CONTAINER PLANT FOR F3

FACTORY AT INVITE FACILITY

Process Equipment Container (PEC) Process Equipment Assembly (PEA)

Docking Station PEC – BASF/Polymer

PEC – Bayer/Pharma

CONTAINER PLANTS

– POTENTIAL FOR COST REDUCTION?

Lower interest rates

Faster time to market

(“50% idea”)

Wo

rkfl

ow

Ba

sed

on

Mo

du

lar

Co

mp

on

en

ts Process Selection

Modular Assembly Planning

Preassembling Modules

Short Field Installation

Start-up

Optimal Configuration Selection

More efficient embedding of

smart production technologies

Standardized infrastructure: fixed,

small-serial manufacturing costs

Risk depends on capacity risk [%] > risk [%]

NPV ECV

cash

time risk [%]

Compactness

Finechemical Case – Capital Investment

Microreactor operation higher investment cost due to higher cost of more

advanced flow reactor, with 60% yield due to smaller reactor, lower cost

Evotrainer enables ~15% lower capital investment than conventional plant

Evotrainer gives

opportunity for

micro to have

comparable

investment cost

I. Vural Gursel, V. Hessel, Q. Wang, T. Noel, J. Lang, Green Proc. Synth. 1, 4 (2012) 315

Finechemical Case – Operating Cost

Microreactor lower raw material (excess of KHCO3 3 fold instead of 6 fold) and

labour requirement, with 60% yield significant raw material cost reduction

High value product example, raw material cost dominates, Evotrainer effect seen

small


Microreactor operation, 60% yield highest cash flow due to lowest operating cost

Evotrainer enables slightly higher cash flow due to investment cost difference

Finechemical Case – Cumulative Cash Flow

Flow optimised

Small-scale flow

Batch

Container Conventional


Reduction of risk, construction period – Evotrainer enables ~40% higher NPV

Microreactor operation although higher risk still higher NPV achieved due to lower

operating cost

Fine Chemical – NPV

Flow optimised

Small-scale flow

Batch

Container Conventional

ca. 40%


Evotrainer advantageous for fine-chemical and pharma production

Bulk-chemical not profitable at this low production rate

3 Chemical Applications

PAGE 64

Pharmaceutical

Fine-chemical

Bulk-chemical

2,4-dihydroxybenzoic acid

adipic acid

naproxen

All in flow

ca. 25%


GREEN PROCESSING & SYNTHESIS

TOPICS

• Sustainable & Green Chemistry, Flow Chemistry

• Advanced, Asymmetric and Bio-inspired Synthesis

• Chemicals from Biomass, White Biotechnology

• Catalysis + Smart Processes for Green (Sustainable) Chemistry

• Green Processing, Novel Process Windows

• Micro Process Technology , Process Intensification

• Alternative Energy (MW, US) and Non-Conventional Media (IL, scF)

• Fuel Cells and Hydrogen Economy

• Photochemistry, Photovoltaics, Energy Storage

• Environmental Chemistry and Toxicology

EDITOR-IN-CHIEF

• Volker Hessel, Eindhoven University of Technology / NL

EDITORS

• Whei Zhang, Boston Center for Green Chemistry / USA

• Galip Akay, Newcastle University Newcastle upon Tyne / UK

• Yi Cheng, Tsinghua University / CN

• Michael C. Cann, University of Scranton / USA

• Isabel Arends, University of Delft / NL

• Dana Kralisch, University of Jena / D

• Giancarlo Gravotto, University of Turino / I

• Christophe Serra, University of Strasbourg / F

• Basu Saha, South Bank Uinversity London / UK

Dr. Q. Wang, Postdoc

T. Illg, PhD

B. Cortese, PhD

P. Tambarussi Baraldi Postdoc

L. Borukhova, PhD

Dr. T. Noel, Assistant professor

I. Vural, PhD

I. Dencic, PhD

S. Stouten, PhD

Acknowledgement to the Group:

Micro Flow Chemistry and Process Technology

S. Van Veen, Master

M. Shang, PhD

B. Spasova, PhD at IMM/TUD

J. Tibhe, PhD

A. Carlos-Varaz Master

H. Fu, Master

A. Hemert, Secretariat

J. Smit, Editorial Assistant

E. Shahbazali PhD

chemical and process-design intensification in flow - seen

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