Thalesnano Overview Aug 2013

Extending the Boundaries Of Organic Synthesis With Flow Chemistry

Heather Graehl, MS, MBA Director of Sales North America ThalesNano North America

Who are we?

•  ThalesNano is a technology company that gives chemists tools to perform novel, previously inaccessible chemistry safer, faster, and simpler.

•  Market leader: 800 customer install base on 6 conDnents. •  33 employees with own chemistry team. •  10 years old-‐most established flow reactor company.

•  R&D Top 100 Award Winner.

Customers (>800 worldwide)

What is flow chemistry?

What is flow chemistry?

Performing a reaction continuously, typically on small scale, through either a coil or fixed bed reactor.

Reactants

Products

By-products

Traditional Batch Method

Gas inlet

Reactants

Products

By-products

Batch vs. Flow

Better surface interaction Controlled residence time Elimination of the products

Flow Method

H-Cube Pro™

Catalyst screening

Parameter scanning: effect of residence time to the conversion and selectivity

Catalyst Flow rate / mL/

min

Residence time / sec

Conc. / mol/dm3

Conv. / %

Sel. / %

IrO2 2 9 0,2 52 69

Re2O7 2 9 0,2 53 73

(10%Rh 1% Pd)/C

2 9 0,2 79 60

RuO2 (activated)

2 9 0,2 100 100

1 18 0,2 100 99

0,5 36 0,2 100 98

Ru black 2 9 0,2 100 83

1% Pt/C doped with Vanadium

2 9 0,2 100 96

1 18 0,2 100 93

0,5 36 0,2 100 84

Conditions: 70 bar, EtOH, 25°C

Selective aromatic nitro reduction

Increase and decrease of residence time on the catalyst cannot be performed in batch

Heating Control

Lower reaction volume. Closer and uniform temperature control

Outcome:

Safer chemistry. Lower possibility of exotherm.

Batch

Flow

Larger solvent volume. Lower temperature control.

Outcome:

More difficult reaction control. Possibility of exotherm.

Heating Control

Lithium Bromide Exchange

Batch

Flow

•  Batch experiment shows temperature increase of 40°C. •  Flow shows little increase in temperature.

Ref: Thomas Schwalbe and Gregor Wille, CPC Systems

Industry Perspective

Survey Conducted

Small scale: §  Making processes safer §  Accessing new chemistry

§  Speed in synthesis and analysis

§  AutomaDon

Large scale: §  Making processes safer §  Reproducibility-‐less batch to batch variaDon

§  SelecDvity

Why move to flow?

Survey Conducted

What chemistries?

Difficult to perform chemistries

•  Low temperature exothermic reactions •  Reactions with gases •  Very slow reactions or unaccessible chemistry •  Reactions with selectivity issues

Approx. 30% of reactions!

What are our drivers?

•  ThalesNano is specialized on designing reactors around specific chemistries where reacDons in flow would be highly beneficial

Exothermic Reactions

• Safety • New chemistry • Simplicity

Endothermic Reactions

• New chemistry • Speed • Green

Reactions with gases

• Safety • Simplicity • Speed • Green

Scale up

• Safety • Selectivity • Reproducibility • Speed

Reaction Line

150°C, 100 bar (1450 psi) H2, CO, O2, CO/H2, C2H4, CO2. Reactions in minutes. Minimal work-up.

-70 - +80C O3, Li, -N3, -NO2

Safe and simple to use. Multistep synthesis. 2 step independant T control.

450°C, 100 bar (1450 psi) New chemistry capabilities. Chemistry in seconds. Milligram-kilo scale Solve Dead-end chemistry.

H-Cube Pro & Gas Module: Reagent gases

Phoenix Flow Reactor: Endothermic chemistry

IceCube: Exothermic Chemistry

Catalysis reactor: Modular: H-Cube Pro

H-Cube Pro H2 Generation 150°C, 100 bar Hydrogenation Selective C-C coupling

Gas Module 12 Extra gases 100 bar

Phoenix Module 450°C Novel heterocycles

Automated injection & collection. Optimization

H-Cube Midi H2 Generation 150°C, 100 bar Scale Up

H-Cube Pro

H-Cube Pro Overview

•  HPLC pumps continuous stream of solvent •  Hydrogen generated from water electrolysis •  Sample heated and passed through catalyst •  Up to 150°C and 100 bar. (1 bar=14.5 psi)

Hydrogenation reactions: § Nitro Reduction § Nitrile reduction § Heterocycle Saturation § Double bond saturation § Protecting Group hydrogenolysis § Reductive Alkylation § Hydrogenolysis of dehydropyrimidones § Imine Reduction § Desulfurization

No More Hydrogen Cylinders

•  Large cylinders contain 4360 litres of compressed H2

•  They are a severe safety hazard •  H-Cube doesn’t use gas cylinders •  Only water •  Clean •  No transportation costs •  Low energy •  Safe •  Just 2 mL H2 @ 1bar

Hydrogen generator cell §  Solid Polymer Electrolyte

High-pressure regulating valves

Water separator, flow detector, bubble detector

Catalyst System - CatCart®

• Benefits •  Safety •  No filtration necessary •  Enhanced phase mixing

• Over 100 heterogeneous and Immobilized homogeneous catalysts

10% Pd/C, PtO2, Rh, Ru on C, Al2O3 Raney Ni, Raney Co Pearlmans, Lindlars Catalyst Wilkinson's RhCl(TPP)3 Tetrakis(TPP)palladium Pd(II)EnCat BINAP 30

• Different sizes • 30x4mm • 70x4mm (longer residence time or scale up)

• Ability to pack your own CatCarts • CatCart Packer (with vacuum) • CatCart Closer (no vacuum)

New Software with H-Cube Pro

Timer Hydrogen Variability

Valve control Data saving Chemistry Guide

H-Cube Pro = higher throughput

2 cells for higher hydrogen production: 60 mL/min

H-Cube Pro: Higher temperature capability

H-Cube Pro: Selectivity with lower temp control

T (oC) p (bar) Flow rate (ml/min) Conversion (%) B Selectivity (%)

20 1, controlled 1 37 99 20 1, controlled 2 65 93 20 1, controlled 3 87 77

Solvent Conc. Temp. (°C) Pressure (bar)

Flow Rate (mL/min)

Product Distribution (%, GC-MS)

A B C EtOH 0.1 M 10 10 1 0 100 0

H-Cube

H-Cube Pro

Simple Validation Reactions (out of 5,000)

10% Pd/C, RT, 1 bar Yield: 86 - 89% Alternate reductions Ketone: Pt/C Aromatic: Ru/O2

Raney Ni, 70°C, 50 bar, 2M NH3 in MeOH, Yield: >85%

Simple Validation Reactions (out of 5,000)

10% Pd/C, 60˚C, 1 bar Yield: >90%

Batch reaction of {3-[(2-carbazol-9-yl-acetylamino)-methyl]-benzyl}-carbamic acid benzyl ester Reagent: H2, catalyst: 10% Pd/C, EtOH, 1 atm, Yield: 76 % Conn, M. Morgan; Deslongchamps, Ghislain; Mendoza, Javier de; Rebek, Julius; JACSAT; J. Am. Chem. Soc.; EN; 115; 9; 1993; 3548-3557.

Raney Ni, 80˚C, 80 bar Yield: 90%

Batch reference: Reagent: HCOONH4, catalyst: 10% Pd/C, solvent: MeOH, Reaction time: 30 min, 1 atm. Yield: 78 % Kaczmarek, Lukasz; Balicki, Roman; JPCCEM; J. Prakt. Chem/Chem-Ztg.; EN; 336; 8; 1994; 695-697

H-Cube® Reaction Examples

Batch: 200°C, 200 bar, 48 hours

Batch: 150°C, 80 bar, 3 days

Chemoselective hydrogenations

Selective reduction in presence of benzyl protected O or N 5% Pt/C, 75°C, 70 bar, 0,01M, ethanol,no byproduct Yield: 75%

Batch reference: Reagent: aq. NaBH4, Solvent: THF; 0°C, Yield: 76,1 % Nelson, Michael E.; Priestley, Nigel D.; JACSAT; J. Am.

Chem. Soc.; EN; 124; 12; 2002; 2894-2902

Route A: Raney Ni, abs. EtOH, 0,01 M, 70 bar, 25°C. Yield: 80%

Route B: Raney Ni, abs. EtOH, 0,01 M, 70 bar, 100°C. Yield: 85%

No batch reference

Selective Hydrogenations

Conditions: 1% Pt/C, 70 bar, 100°C, residence time 17s Results: 100% conversion, 97% yield


Conditions: Au/TiO2, 70 bar, 30°C, residence time 17s Results: 100% conversion, 100% yield

H-Cube® - Chemoselective hydrogenations

Ürge, L.et al. submitted for publication

Selective hydrogenation of the double-bond

Selective hydrogenation to afford oxime

Selective hydrogenation of the double-bond

Selective Hydrogenations

Conditions: 10% Pd/C, 70 bar, 0°C, residence time 16s Results: 100% conversion, 100% yield

Conditions: 1% Pt/C, 70 bar, 30°C, residence time 11-17s Results: 100% conversion, 100% yield


Ürge, L.et al. submitted for publication

H-Cube® - Chemoselective hydrogenations

Nitro group reduction in the presence of a halogen

Nitro group reduction in the presence of Cbz-group

Nitro group reduction without retro-Henry as a

side-reaction

Selective dehydrochlorination

Flow rate

(mL/min)

Pressure (bar) Temperature (oC)

Bubdet Catalyst Amount A (%)

Amount B (%)

Amount C (%)

Amount D (%)

1 20 (∆p:5 bar) 110 50 10% Pd/C 26.7% 61.5% - 7% 1 20 (∆p:3 bar) 110 50 1% Pd/C 61,90% 29,40% - 2,50% 1 20 (∆p:13

bar) 110 50 5% Rh/C 78.9% 5.1% - 9.2%

1 20 (∆p:10 bar)

110 50 5% Pd/C 26.7% 60.9% - 6.7%

1 20 (∆p:5 bar) 110 50 5% Pd/C(S) 25% 63.4% - 6.6%

Objective: Match similar selectivity of 60% but without additives of CsF, S, K2CO3 and PPh3

Partial saturation of heterocycles

Optimised reaction parameters: -  H-Cube Pro -  Temperature: 100oC -  Pressure: 100 bar -  Hydrogen amount: Maximum

Results:

•  Generate new non-planar molecules from existing stocks. •  New molecules have new Log P and other characteristics.

•  Cheap •  Clean •  Quick •  Only on H-Cube: High P + Selective control.

Flow rate (ml/min) Conversion % of A % of B % of C 0.3 100% 100 0 0 0.5 100% 92 8 0 1.0 100% 86 14 0

Deuteration

Substrate Product Deuterium content(%)

Isolated yield / %

99 99

97 98

93 97

96 98

96 99

Mándity, I.M.; Martinek, T.A.; Darvas, F.; Fülöp, F.; Tetrahedron Letters; 2009, 50, 4372–4374

H-Cube Autosampler™

Gilson 271 Liquid Handler §  402 single Syringe pump (10 mL) §  Direct GX injector (Valco) §  Low-mount fraction collection (Bio-Chem) §  Septum-piercing needle §  Static drain wash station §  Tubes, connectors, fittings

Open vial collection Collection through probe (into closed vial)

H-Cube Midi™ reactor for scale-up

Parameters: -  p= 1-100 bar -  T=10-150°C -  v=0.1-3 ml/min - c=0.01-0.1 M - H2 production = up to 60ml/min - CatCarts = 30x4mm or 70x4mm

Parameters: -  p= 1-100 bar -  T=25-150°C -  v=5-25 ml/min - c=0.05-0.25 M - H2 production = up to 125ml/min - CatCarts = 90x9.5mm

Milligram to Gram Scale

Half Kilogram Scale

Conversion: 90-95% (TLC) Purity: 70% (LC-MS) without work-up

Batch parameters: K3PO4, TBA-Br, Pd(OAc)2, DMF, 2 hours, 130 °C Reference: (Zim, Danilo; Monteiro, Adriano L.; Dupont, Jairton; Tetrahedron Lett.; EN; 41; 43; 2000; 8199-8202)

Suzuki-Miyaura C-C cross coupling:

Sample reactions

Br

N O 2 B

O H O H

N O 2 CatCart TM 70*4 mm Pd EnCat TM BINAP 30, 2-propanol, TBAF, 80°C, 20 bar, 0.05M, 0.5 ml/min

+

Selective Suzuki coupling (Cl, Cl)

The condiDons were:

1 equivalent of 2,6-‐dichloroquinoxaline with 1.2 equivalent of o-‐Tolylboronic acid

ConcentraDon set to 0.02M

Solvent: Methanol

Base: NaOH

AnalyDcs: GC-‐MS

Flow rate (ml/min)

Pressure Temperature Catalyst Base

Result (bar) (oC) LC-‐MS, 220nm

0.8 20 100 Fibrecat 1007

(70mm) 3 ekv

Conversion: 82% SelecDvity: 48%

0.3 20 100 Fibrecat 1007

(70mm) 3 ekv


0.8 20 100 Fibrecat 1035

2.5 ekv Conversion: 16%

(30mm) SelecDvity: 100%

0.8 20 100 Fibrecat 1029

(30mm) 2.5 ekv


0.8 20 100 Fibrecat 1048

(30mm) 2.5 ekv


0.8 20 100 10% Pd/C



0.5 20 50 Fibrecat 1048

2.5 ekv Conversion:17%

(30mm) SelecDvity: ~100%

0.5 20 100 Fibrecat 1048


(30mm) SelecDvity: ~100%

0.2 20 100 Fibrecat 1007



0.2 20 100 Fibrecat 1007



0.2 20 100 Fibrecat 1029



Purity (LCMS): 63%

Batch parameters: Pd(OAc)2, PPh3, TEA, DMF, 3 days, 110°C, yield: 70% Reference: J. Chem. Soc. Dalton Trans., 1998, 1461-1468 J. Chem. Soc. Dalton Trans., 1998, 1461-1468

Heck C-C cross coupling:

Sample reactions

CatCartTM: Pd (PPh3)4, TBAF, 2-propanol, 0.05M, 100oC, 1 bar, 0.2 ml/min.

Catalysis reactor: Modular: H-Cube Pro

H-Cube Pro H2 Generation 150°C, 100 bar Hydrogenation Selective C-C coupling

Gas Module 12 Extra gases 100 bar

Phoenix Module 450°C Novel heterocycles

Automated injection & collection. Optimization

H-Cube Midi H2 Generation 150°C, 100 bar Scale Up

Gas Module

•  Versa7le: Compressed Air, O2, CO, C2H4, SynGas, CH4, C2H6, He, N2, N2O, NO, Ar.

•  Fast: ReacDons with other gases complete in less than 10 minutes

•  Powerful: Up to 100 bar capability.

•  Robust: All high quality stainless steel parts.

•  Simple: 3 budon stand-‐alone control or via simple touch screen control on H-‐Cube Pro™.

Use of Gas Module Attached to the H-Cube Pro™

Gas Module HPLC pump H-Cube Pro™

Filter included Check valve included

Problems with Oxidation

Alcohol oxidation: Optimization

Pressure Temp. (oC) CatCart Conversion Selectivity

40 25 1 % Au/TiO2 0 – 40 65 1 % Au/TiO2 6.5 >85 40 25 1 % Au

/Fe2O3 0 – 40 65 1 % Au

/Fe2O3 12.7 0 40 25 5 % Ru

/Al2O3 2.8 ~100 40 65 5 % Ru

/Al2O3 3.6 ~100 100 65 5 % Ru

/Al2O3 2.7 ~100 100 100 5 % Ru

/Al2O3 8.5 ~100 100 140 5 % Ru

/Al2O3 15.5 ~100 100 65 1 % Au/TiO2 5.6 84 100 100 1 % Au/TiO2 47.2 93 100 140 1 % Au

/TiO2 ~100 93 100 65 1 % Au

/Fe2O3 4 0 100 100 1 % Au

/Fe2O3 31 7 100 • Area% of desired product in GC-MS / (100 – Area% of reactant in GC-MS)

General conditions: H-Cube Pro with Gas Module, 50 mL/min oxygen gas, 1 mL/min liquid flow rate (0.05M in acetone, 20 mL sample volume), CatCart: 70mm., 1 % Au/TiO2 (cartridge: 70mm, THS 01639),

Batch ref.: Oxygen; perruthenate modified mesoporous silicate MCM-41 in toluene T=80°C; 24 h; Bleloch, Andrew; et al. Chemical Communications, 1999 , 8,1907 - 1908

Very fast addition of alcohol to gold surface. Alkoxide formation.

Aromatization of heterocycles

Reaction parameters were tested: -  H-Cube Pro with and without GasModule -  Oxidizing agent: Hydrogen-peroxide and Oxygen -  Catalyst: MnO2, Amerlyst 36, Au/TiO2 -  Solvent: Acetone/H2O2, Acetone -  Temperature 60-150oC, pressure 20-50 bar, flow rate 1 ml/min, concentration: 0.05 mmol/ml

Oxidizing agent Solvent Catalyst

Temperature (oC)

Pressure (bar) Conversion Comment

MnO2 Acetone MnO2 60 20 82% Blockage ager 10 minutes

H2O2 Acetone -‐ H2O2

(4-‐1) Au/TiO2 70 20 68% ager 1 run 78% ager 2 run

H2O2 Acetone -‐ H2O2

(4-‐1) Au/TiO2 100 30 68% ager 1 run 98% ager 2 run

The catalyst was reacDvated with H2O2 between the runs.

O2 (10 ml/min) Acetone Au/TiO2 75 11 8%

O2 (10 ml/min) Acetone Au/TiO2 150 11 95%

Ager 10 minutes the conversion was dropped to

50%

O2 (50 ml/min) Acetone Au/TiO2 150 20 > 98%

Ø  Conditions: 100oC, 30 bar, CO gas, 0.5 ml/min liquid flow rate, 0.01 M in THF Ø  Catalyst: Polymer supported Pd(PPh3)4 Ø  Reference test was managed on X-Cube Ø  Reaction was repeated Ø  Different gas flow rates were tested

Results

Aminocarbonylation

ReacDon HC-‐Pro with gas module (CO flow rate)

XC reference

10 ml/min

30 ml/min

60 ml/min

30 ml/min

30 ml/min

60 ml/min

60 ml/min

60 ml/min

Conversion % 60 65 79 66 62 79 79 82 0

Accessing New Molecules or Chemical Space

Heterocyclic rings of the future, J. Med. Chem., 2009, 52 (9), pp 2952–2963.

•  3000 potential bicyclic systems unmade • Many potential drug like scaffolds Why? • Chemists lack the tools to expand into new chemistry space to access these new compounds. •  Time • Knowledge

The quest for novel heterocycles

•  Standard benzannulation reaction •  Good source of:

•  Quinolines •  Pyridopyrimidones •  Naphthyridines

→ Important structural drug motifs

Disadvantages: • Harsh conditions • High b.p. solvents • Selectivity • Solubility

W. A. Jacobs, J. Am. Chem. Soc.; 1939; 61(10); 2890-2895

High T Chemistries – in Batch

• Replacement of diphenyl ether (b.p: 259°C) with THF (b.p.: 66 °C)

Cyclization conditions: a: 360 °C, 130 bar, 1.1 min b: 300 °C, 100 bar, 1.5 min c: 350 °C, 100 bar, 0.75 min

Pyridopyrimidinone Quinoline

No THF polymerization!

Batch conditions: 2 hours

Gould-Jacobs Reaction – in Flow

The nature of the substituents is critical because they increase or decrease the nucleophilicity of the ring: Electron donating groups increase yields, Electron withdrawing groups decrease yields.

50

Process exploration

• Meldrum’s acidic route to pyridopyrimidones and to hydroxyquinolines

Cyclization conditions: a: 300 °C, 160 bar, 0.6 min b: 300 °C, 100 bar, 0.6 min c: 360 °C, 100 bar, 1 min d: 350 °C, 130 bar, 4 min e: 300 °C, 100 bar, 1.5 min

Lengyel L., Nagy T. Zs., Sipos G., Jones R., Dormán Gy., Ürge L., Darvas F., Tetrahedron Lett., 2012; 53; 738-743

New Scaffold Generation

5 novel bicyclic scaffolds generated-fully characterized. Many more to follow

Phoenix Flow Reactor: High temperature synthesis

Powerful: Up to 450°C

Versatile: Heterogeneous and homogeneous capabilities.

Fast: Reactions in seconds or minutes.

Innovative: Validated procedure to generate novel bicyclic compounds

Simple: 3 button stand-alone control or via simple touch screen control on H-Cube Pro™.

Ring closure on aryl NH : key step •  Mitsunobu reaction or traditional heating with T3P did not

furnish the bicyclic heterocycle. •  Reaction proceeded smoothly in Phoenix reactor at 300oC with

65% yield despite requirement for the cis amide conformer in transition state.

Mitsunobu Reaction

N-Alkylation Reaction

RaNi 70mm 200C, 80bar 0.5ml/min

55

C-H Activation

•  Objectives: to find a cheap and green alternative of performing 1 step

alkylation reaction via C-H activation.

•  Relevance: used for generation of novel compounds, via C-H activation

untouched positions on rings can be activated.

•  Main problems: •  strong bond between carbon and hydrogen atoms

•  Multistep reaction

•  Require expensive metal catalysts (Pd, Pt)

•  Selectivity is an issue

•  Results: form another C-C or C-X bond at a position not favored by

conventional alkylation methods

56

Reaction pathway using Raney-Ni catalyst

Advantages of Raney-Nickel: •  Cheaper than Pd, Pt containing catalysts •  Differently preactivated Raney-Ni catalyst can give more

flexibility – selectivity issues

But: Pyrophoric!

57

Optimizing the reaction conditions:

•  0.1M Indole solution in ethanol, RaNi 4200 Catalyst, GC-MS results

Reach higher selectivity: Protect the N-atom with TMS-Cl Result: 90% conversion with 80%

selectivity (300 °C, 100 bar, 0.5 mL/min,

isolated yield: 76.5%)

58

Alkylation of 2-methyl-indoline

The total amount of dialkylated products was 18%.

Alkylation coupled with dehydrogenation

59

Ring closuring of 2-methyl-indole with 1,3-butanediol

Ring closure is coupled with hydrogenation of double bond

Diels Alder

•  Diels-Alder reactions usually require long reaction times.

• This reaction time could be reduced to 5 minutes at 250°C using toluene.

• .Product isolated in near quantitative yield.

• Reaction also possible using lower boiling solvents (MeCN, THF, DME) with same result using higher pressures (200 bar).

Fischer-Indole Synthesis: Scale Out

cf. MW reaction: Bagley, M. C.; et al. J. Org. Chem. 2005, 70 , 7003

In AcOH/2-propanol (3:1) (0.5M) 150 °C, 60 bars,

1.0 mL min-1 (4 min res. time) 88% isolated yield

Continuous Flow Results (4 mL or 16 mL Coil) Scale-up

200 °C, 75 bars, 5.0 mL min-1 (~3 min res. time)

96% isolated yield

25 g indole/hour

High temperature reactions

Conditions: p = 70 bar T = 270°C v = 0.4 mL/min c = 0.04 M (NMP) Result: 82% yield

Kappe, O. C. et al. Eur. J. Org. Chem., 2009, 9, 1321-1325.

X-Cube FlashTM – Kolbe Synthesis Conditions: p = 60 bar T = 180°C v = 4 mL/min Residence time: 440 s c = 0.49 M (H2O) Best result: 51% conversion

Kappe, O. et al. Chem. Eng. Technol. 2009, 32(11), 1-16.

X-Cube FlashTM – SNAr reaction

High Energy

Reac7ons

Ice Cube Modules

Ozone Module generate O3 from O2 100 mL/min, 15 % O3

Cooled Reactor Module – teflon tube on peltier coolers; -70°C.

Pump Module – Peristaltic or Gear Pump Optional: 1 or 2

Versa7le: 2 op7ons

A

B C

A B

C

D

Pre-cooler/Mixer Reactor

-70-+80ºC

-70-+80ºC -30-+80ºC

Potential Apps: Azide, Lithiation, ozonolysis, nitration, swern oxidation

Safe reaction of azides using Ice-Cube

•  2 Step Azide Reaction in flow •  No isolation of DAGL •  Significantly reduced hazards

TKX50

Ozone concentration critical!

Reaction parameters: Flow rate = 0,7 ml/min Quench flow rate = 1,4 ml/min O3 flow rate = 17,5 ml/min (~2 eq.) T = -5 oC cEugenol = 0,05 M cNaBH4 = 0,05 M Solvent = EtOH Results: Conversion = 100 % misolated = 326,2 mg mmax. yield = 504 mg Isolated yield = 65 % Purity of isolated product = 98 % *

Nitration in flow

Pump A Pump B Temperature (oC)

Loop size (ml)

Conversion (%)

SelecDvity (%)

SoluDon Flow rate (ml/

min) SoluDon Flow rate (ml/

min)

ccHNO3 0.4 1g PG/15ml ccH2SO4 0.4 5 -‐ 10 7 100

0 (different products)

1.48g NH4NO3/15ml ccH2SO4 0.7

1g PG/15ml ccH2SO4 0.5 5 -‐ 10 13 100 100

1.48g NH4NO3/15ml ccH2SO4 0.5

1g PG/15ml ccH2SO4 0.5 5 -‐ 10 13 50 80 (20% dinitro)

70% ccH2SO4 30% ccHNO3 0.6

1g PG/15ml ccH2SO4 0.5 5 -‐ 10 13 (3 bar) 100 100

70% ccH2SO4 30% ccHNO3 0.6

1g PG/15ml ccH2SO4 0.5 5 -‐ 10 13 (1 bar) 80

70 (30% dinitro and nitro)

Batch reference: 30ml ccH2SO4, 1g PG, 1.48g NH4NO3, 5-10oC 10 min, Conversion: 91%

Flow University

•  PracDcal Lab Manual

•  PresentaDon tutorial •  Background notes •  EducaDonal Videos

q  In English q  In Mandarin Chinese

q SubDtled

THANK YOU FOR YOUR ATTENTION!!

ANY QUESTIONS

Thalesnano Overview Aug 2013

Technology

soludon flow

gas module

flow rate

h2 production

raney ni

flow chemistry

residence

reaction time