Thales Nano H Cube Hydrogenation Reactor ThalesNano Hydrogen Manual

H-Cube® - Next Generation Hydrogenation

User Manual HC-2.SS

Declaration of Conformity Manufacturer’s name:

THALES Nanotechnology Inc. Address of manufacturer:

Budapest, H-1031. Záhony u. 7. Hungary Product:

H-Cube Continuous hydrogenation equipment Type of product:

HC-2 As the developer, designer and manufacturer of the above detailed equipment, THALES Nanotechnology Nanotechnolo gy Inc. declares that the product complies with the following requirements and specifications Equipment for potentially explosive atmospheres • Ordinance - 94/ 9 EC MSZ EN 1127-1: 2000 MSZ EN ISO 12100-1:2004 MSZ EN ISO 12100-2:2004 MSZ EN 60079-10: 2003 Pressure equipment Ordinance - 97/23 EC • Safety requirements for electrical equipment for • laboratory use MSZ EN 61010-1 : 2002 The verification test carried out and has been recorded in the document No.: HCMF-001-001 The CE marking is affixed to the rear panel of the equipment. st

Budapest, October, 1 2005

H-Cube® User Manual

v. 2. 7.

page:2 of 75

This manual provides instructions on how to use H-Cube® Continuous hydrogenation equipment model

HC-2.SS

SS-reaction line version* Software version: 2.5.0.6.**

*this model is a version of the HC-2 Continuous hydrogenation equipment assembled so that the reaction line wetted parts are made of either Stainless steel or TEFLON material ** or later

User Manual: ver 2.7. Issued on: 2009.10.


v. 2. 7.

page:3 of 75

Contents 1. General Description Description ................................................................................ .................................................................................................. .................. 6 1.1. Introduction Introduction................................................ ............................................................................ ......................................................... .............................6 1.2. H-Cube® System Overview ............................................................................... ............................................................................... 6 2. Overview of Parts........................................................ .................................................................................... .............................................. .................. 8 2.1. Touch-screen Touch-screen Interface ..................................................... ................................................................................... ................................. ... 9 2.1.1. Command Field ......................................................... ..................................................................................... .................................... ........ 10 2.1.2. Information field .......................................... ...................................................................... ................................................... ....................... 11 2.1.3. Control Fields ................................................................. ............................................................................................... ................................ 11 2.1.4. Hydrogen Field ..................................................... ................................................................................. ........................................ ............ 12 2.1.5. The service screen ................................................ ............................................................................ ........................................ ............ 13 2.2. Solute Delivery System ........................................................ ................................................................................... ........................... 14 2.3. Reaction Box ............................................ ........................................................................ ....................................................... ........................... 15 2.3.1. Electrolytic Electrolytic Cell .................................................. .............................................................................. ............................................ ................ 15 2.3.2. Water Separator Separator Unit...................................................... .................................................................................... ................................ 15 2.3.3. Heating Unit....................................................... ................................................................................... ............................................ ................ 15 2.3.4. Catalyst Cartridge...................................................... .................................................................................. .................................... ........ 16 2.3.5. Water level indicator ...................................................... .................................................................................... ................................ 17 2.3.6. Available sorts of CatCarts® CatCarts® ......................................................................... ......................................................................... 17 3. Installation Installation................................ ............................................................ ........................................................ ................................................... .......................18 3.1. Delivery Content ............................... ........................................................... ........................................................ .................................... ........ 18 3.2. Unpacking H-Cube® .................................................... ................................................................................ .................................... ........ 19 3.3. Installing H-Cube® ........................................................ ...................................................................................... ................................ 20 4. Operating Instructions Instructions ..................................................... ................................................................................. ........................................ ............ 26 4.1. Initiating H-Cube® ................................................ ............................................................................ ............................................ ................ 27 4.2. Operating H-Cube®...................................................... .................................................................................. .................................... ........ 33 4.3. Shutting-down Shutting-down H-Cube® ..................................................... ................................................................................ ........................... 36 5. Examples for Hydrogenation Hydrogenation Protocols....................................................... ................................................................... ............ 38 5.1. Self-test Procedure Procedure....................................................... ................................................................................... .................................... ........ 38 5.2. Nitro Reduction..................................................... ................................................................................. ............................................ ................ 38 5.3. N-benzyl N-benzyl De-protection of 4-anilino-1-benzylpipe 4-anilino-1-benzylpiperidine ridine .................................. .................................. 41 5.4. A Starters guide to what parameters can be be used when reducing various functional functional groups ................................................................. ............................................................................................. .................................... ........ 42 6. Advanced Advanced Use...................................................... Use.................................................................................. ................................................... ....................... 43 6.1. Optimization Optimi zation of Reaction Conditions for Enhanced Product Conversion ......... ....... .. 43 6.2. Further Reaction Conditions for Enhanced Product Conversion .............. ....... .............. ....... 44 6.3. Recycling the Reaction Reaction Mixture ...................................................... ...................................................................... ................ 44 7. Troubleshooting Troubleshooting ....................... . .................................................. ........................................................ ................................................... ....................... 46 7.1. Touch-screen Touch-screen Interface Error Messages .......................................................... .......................................................... 46 7.2. Problems in the H-Cube® System........................................................ .................................................................... ............ 47 47 8.Solvent 8.Solvent Resistance .......................... . ..................................................... ........................................................ ............................................ ................ 48 9. Detecting a blockage in the H-Cube® ..................................................... ..................................................................... ................ 49 9.1. A blockage blockage in the back-pressure regulator ..................................................... ....................................................... 50 9.2. A blockage in the reaction line before the back-pressure regulator regulat or ............... ........ ......... .. 50 10. Maintenance Maintenance ...................................................... .................................................................................. ................................................... ....................... 53 10.1. Daily Maintenance Maintenance Checks ................................. ............................................................. ............................................ ................ 53 H-Cube® User Manual

v. 2. 7.

page:4 of 75

10.2. General Maintenance Maintenance ..................................................................... ..................................................................................... ................ 53 10.2.1. Changing the Teflon membrane in system valve ......................................... ......................................... 53 10.2.2. Clearing air from the HPLC pump head....................................................... head....................................................... 55 10.2.3. Cleaning or replacing the Inlet frit ........................................................ ................................................................ ........ 56 10.2.4. Cleaning the Inlet-line filter or the PTFE eluent filter ................................... ................................... 56 10.2.5. Changing the check-valve check-valve ........................................................... ........................................................................... ................ 57 57 10.2.6. Piston backflushing backflushing ...................................................... .................................................................................... ................................ 58 10.2.7. Useful hints:..................................................... ................................................................................. ............................................ ................ 58 11. Necessary Servicing ......................................... ..................................................................... ................................................... ....................... 59 12. Replacement Replacement Parts ............................................................... ............................................................................................. ................................ 60 13. Accessories....................... Accessories................................................... ........................................................ ....................................................... ........................... 60 14. Technical Data ..................................... ................................................................. ........................................................ .................................... ........ 61 15. Warranty Information ...................................................... .................................................................................. .................................... ........ 62 16. Appendices Appendices .............................................................. .......................................................................................... ............................................ ................ 63 Appendix 1: The service window – an explanation ..................................................... ..................................................... 63 Appendix 2: Control of the H-Cube® from an external source ................................... ................................... 64 1. General .................................................................. .............................................................................................. ............................................ ................ 64 2. List of errors ....................................... ................................................................... ........................................................ .................................... ........ 65 3. RS232 command documentation - quick reference............................................ ............................................ 66 4. List of commands commands ............................................ ........................................................................ ................................................... ....................... 67


v. 2. 7.

page:5 of 75

1. General Description 1.1. Introduction Catalytic hydrogenation is the most important technique for the reduction of chemical substances, but is severely limited by the harsh reaction conditions and the potential hazards of catalyst handling. The emergence of combinatorial chemistry methods, by contrast, demands a readily accessible technology that supports automation and highthroughput synthesis on the right scale. In response to these limitations and needs we have developed the H-Cube®, a revolutionary bench-top continuous-flow reactor that can perform a wide range of heterogeneous reductions in conditions of up to 100 bars and 100 ° C, using the electrolytic reduction of protons, as an internal hydrogen source.

1.2. H-Cube® System Overview The H-Cube® system is based on the hydrogenation of a continuous flow of reactant. Additional equipment is needed to introduce the reactant into the H-Cube® device. For the most basic function where only a continuous flow of reactant is flowed through the system, only an additional HPLC pump is required. If you wish to conduct multiple injections of different reactants into a continuous stream of solvent, then a loop injector valve is also required. Both set-ups are outlined in the figure below.

Figure 1a: H-Cube® system setupContinuous-flow mode


v. 2. 7.

Figure 1b: H-Cube® system setupwith loop injector page:6 of 75

Electrolytic water decomposition within the H-Cube® generates high-purity hydrogen in the required quantity, eliminating the need for gas storage. The hydrogen gas and a solution of the reactant are mixed, pre-heated and transferred to a disposable catalyst cartridge ( CatCart® ) that is preloaded with the required heterogeneous catalysts. The product then flows out of the cartridge and is collected in a vial or flask. In most reactions the only work-up required is the evaporation of solvent.

Water Reservoir with level sensors Electrolysis cell

Water separator

Water outlet

Excess H2 outlet

H 2 generation

Pressure control unit

Product collector

CatCart®

Pressure sensor

Closing valve

Valve

P

P

Pre-heater unit

Bubble detector

Pressure sensor

Mixer

Solution inlet

P Pressure sensor

Figure 2: Schematic design of the H-Cube®

The continuous flow of reaction mixture out of the device allows the operator to carry out on-the-spot analysis of the resulting reaction mixture. Reaction parameters can be easily adjusted using a touch-screen interface in order to achieve a better product yield.


v. 2. 7.

page:7 of 75

2. Overview of Parts

8

11 5

10 4

1 2

1. Sample inlet line 2. Inlet pressure sensor 3. Gas check valve 4. Gas / liquid mixer 5. Bubble detector 6. Heater unit 7. CatCart® column c olumn unit 8. System pressure sensor 9. Back pressure regulator 10. Hydrogenated product collector coll ector 11. Touch-screen panel 12. Water reservoir 13. ON/OFF ON/OFF switch 14. Cable connector conn ector ports 15. Excess water wat er container contain er 16. HPLC pump pum p RS232 port 17. External control RS232 port

3 9

6

7

Figure 3: Front view of H-Cube®

16

17

15 13

14

12

FIgure 4: Back view of H-Cube®

The H-Cube® system is composed of three major components: • • •

A Touch-screen Interface The Solute Delivery System The Reaction Box


v. 2. 7.

page:8 of 75

2.1. Touch-screen Interface This user interface is a graphic touch-screen module based on conventional operator interfaces found on HPLC equipment. The touch-screen interface consists of two windows that enable you to manually control all aspects of the reaction while it is in progress, and also view the system parameters. The main window displays a simple flow-chart of the system where operational parameters such as reaction temperature and pressure are displayed, and can be set by the operator. The main window consists of the following main fields: • • • • • •

A command field An information informati on field 3 control fields A display field Water level indicator Combined display/command display/com mand field for Hydrogen handling information field control field

command field

control field

Hydrogen field water level indicator

Figure 5: The main window ( shown in Controlled Mode)


v. 2. 7.

page:9 of 75

2.1.1. Command Field Situated at the top left-hand corner of the touch-screen module, the Command field consists of three functional buttons that give you complete control over the reaction process and also allow you to monitor the system status. The

start/stop

button starts and stops the hydrogenation process.

The shutdown button on the main window shuts-down the system. Before shutting-down, the prompt “ Shutdown: Are you sure?” message appears, under which there is a Yes and and a No button field. Pressing Yes shuts down the system, whilst pressing No halts the shutdown process and takes you back to the main window. The service button takes you to the service window. The service window gives detailed information which may help a technician with a diagnosis of any machine fault. It shows more detailed system characteristics such as the electrolysis cell voltage, the different pressure values within the system, the valve positions, the set temperature, the actual temperature, and the device history. Pressing the back button on the service window brings you back to the main window. The service screen shown in 2.1.5.


v. 2. 7.

page:10 of 75

2.1.2. Information field This field can be found at middle top on the screen and gives information informati on on the status of the instrument. The listed parameters and their possible values are as follows: Messages H2 cells: Valves: Heater: Water flow: Status:

OK/Error OK/Setting/Error Idle/Heating/Error OK/Error Ready/Starting/Running/Stopping/Shutdown

Stabilizing status information: informat ion: three kinds of messages may appear Stabilizing: No hydrogen detected in the system Stable: Hydrogen detected in system Resetting System: Closing hydrogen valve, resetting back pressure valve Status field : ( bottom field with possible messages as below ) Starting Up : The status after after switching on, during initializing process Starting : The status immediately after starting the hydrogenation process Running : During normal hydrogenation Stopping : The status immediately after stopping the hydrogenation process Ready : State of readiness readiness

2.1.3. Control Fields These fields enable you to set the reaction pressure, temperature and flow-rate conditions to the desired levels. Simply adjust the values by pressing the up or down arrow buttons in each of the fields. Pressure regulator : Allows you to set the desired pressure for the reaction, up to 100 bars. Please note that if the HPLC pump is switched-off, the pressure will remain unchanged. Column heater : Allows you to set the desired temperature for the reaction, up to 100 °C. Please note that the displayed temperature is that belonging to the liquid. To view the set temperature value, go to the service screen by pressing the service button. button. Pump flow-rate controller : Allows you to set the pump flow-rate, up to a maximum of 3ml/min.


v. 2. 7.

page:11 of 75

2.1.4. Hydrogen Field The display fields give information informati on on Hydrogen generation and for the water level status as follows: a.)

Hydrogen control field where the internal hydrogen pressure conditions are shown, along with the hydrogen controlling option mode: There are 3 different modes available: * at 0 bar system pressure Full H2 or Controlled mode or No H 2 mode and * at 10 bar to 100 bar range Controlled and No H 2 mode only.

The 3 modes may be accessed by repeated pressing of the mode button. Full H2 mode: gives you the option of performing reactions which may require a larger amount of hydrogen at 1 bar, bar, for example, nitro, without increasing the pressure of the reaction to obtain a larger amount of hydrogen dissolved in the solution for conversion. Full H 2 mode can only be be selected when the pressure regulator is 0 ! 2 mode can Controlled (H2) mode: gives you a stable pressure level at the desired pressure. The hydrogen production is limited and the solubility of the hydrogen is dependant on pressure ( Henry’s Law ). ). At higher pressures a larger concentration of hydrogen will be present in the solution. No H2 mode: gives you the opportunity to try high-pressure continuous-flow reactions without hydrogen and using other heterogeneous catalysts, for example, Suzuki and Heck coupling.

b.) The field for water level detection.

A bar is marked with F – for full and E – for empty referring to the level of water in the reservoir. The normal level is between the E and F positions. Below the E level the software will shut the equipment down with an error message.


v. 2. 7.

page:12 of 75

2.1.5. The service screen

Figure 7: Service window (an example in Controlled Mode)

The service window gives detailed information informati on showing parameters.

complete

data on system

Pressing the back button button on the service window brings you back to the main window. purge button useful for non-automatic, unconditioned operation of water pump. For service purposes and for flushing the water out of the cell( fe.g., in the case of changing DI water to D 2 O, or for f or cleaning). For more technical details please call ThalesNano )

For more details, please refer to Appendix 1. Figure 7b shows an “N/A” value in the bubble detector window because control of the hydrogen is not necessary in Full Hydrogen mode.


v. 2. 7.

page:13 of 75

2.2. Solute Delivery System Solutes can be introduced into the device via two methods: a.) The reagent is dissolved in a solvent solv ent system of the operator’s choice, choi ce, and delivered to the H-Cube® via a conventional HPLC pump. This method of delivery can be used to reduce reagents up to a scale of 100 grams.

Figure 8: HPLC pump

b.) For smaller reagent quantities, in other words, from 1 to 40 mg, you can use an injector system to inject the small amount of solute into a continuous flow of reaction solvent. This method is ideal for carrying out a library step on a large number of smallscale compounds where a heterogeneous hydrogenation is required, for example, hydrogenolysis of a benzyl-protecting group. Each compound is injected into the system at timed intervals, reduced in the device, and collected as different fractions at the end of the reaction.


v. 2. 7.

page:14 of 75

2.3. Reaction Box The reaction box comprises of several custom-built integrated components. Below is a description of the hydrogenation process and the valuable role that these components play: 1) 2) 3) 4)

The Electrolytic Cell The Water Separator The Heating Unit The Catalyst cartridge

2.3.1. Electrolytic Cell ( inside the equipment, not visible for users ) The hydrogen for the reaction is generated through the electrolytic splitting of water in an electrolysis cell. The water is applied to the anode side, and then dissociates, with the protons migrating to the cathode under the effect of the applied voltage. The protons are reduced to produce hydrogen gas, while oxygen, formed by the discharge of hydroxide ions at the anode, is removed from the cell with the recycled water.

2.3.2. Water Separator Unit ( inside the equipment, not visible for users ) The protons migrating through the proton exchange membranes are hydrated depending on the amount of water present in the membrane. Therefore, the hydrogen gas generated at the cathode will contain water that has to be removed before use in the reaction system. This is important as the system may be used to perform watersensitive hydrogenation such as reduction of an imine to the amine without hydrolysis to the aldehyde. To remove the water, the gas liquid mixture is fed into a water separator chamber where upon the liquid deposits at the bottom of the chamber whilst the gas leaves via an outlet at the top.

2.3.3. Heating Unit ( assembled on front panel ) The heating unit heats the reaction solution to the required temperature, set by the operator using the touch-screen module. The heater unit is a “Peltier” heating system which consists of a stainless steel reaction line coil contained within a stainless steel block. The CatCart ® holder screws into the metal block. The metal block has a thermometer inserted within to monitor changes in temperature. The metal block is heated, which in turn heats the reaction line, the column holder and CatCart ® .


v. 2. 7.

page:15 of 75

Figure 9: The heating unit

2.3.4. Catalyst Cartridge The hydrogenation reaction takes place within a proprietary catalyst handling system. This involves the use of disposable Catalyst Cartridge (CatCart®) columns that minimize operator/catalyst handling. The types of catalysts available from ThalesNano include the following basic types: 5 and 10% Pd/C • 5 and 10% Pt/C • Raney nickel • 5% Rh/C • Pd(OH)2 /C (Pearlman’s (Pearlman’s catalyst) catalyst) • Raney cobalt • PtO2 •

Other specialist catalysts are in stock, including catalysts for asymmetric reductions and sulfur-tolerant catalysts. For a full list, please check our website www.thalesnano.com .


v. 2. 7.

page:16 of 75

2.3.5. Water level indicator The water reservoir has a built-in built-i n water water level indicator system assembled optoelectronics using visible ( red ) light. The system has three sensors: Sensor #1: FULL level Sensor #2: close to minimum working level Sensor #3: Empty level

2.3.6. Available sorts of CatCarts® Standard CatCart ® columns, called CatCart®30, contain approximately 140 mg of catalyst. Larger CatCarts® are available in two sizes, CatCart®55 and CatCart®70, containing 280 mg and 350 mg of catalyst, respectively. These larger columns are capable of reducing up to 100 g of some substrates. The cartridge is encased in a column holder that is held tightly in place and can be subjected to pressures in excess of 100 bars.

Figure 10: CatCart®30, CatCart®55 and CatCart®70 Ca tCart®70


v. 2. 7.

page:17 of 75

3. Installation

The H-Cube® has been designed and tested against stringent health and safety standards. To ensure the lifetime of the instrument and to maintain safe usage of the H-Cube®, the following steps should be strictly applied.

3.1. Delivery Content The H-Cube® delivery package includes the following items: 1 • 1 • 1 • 2 • 1 • 1 •

•

2 • 2 • 1 • 1 • 1 • 2 •

• • •

1 1 1

H-Cube® Continuous hydrogenation equipment H-Cube® User Manual Power supply unit Low-voltage connector cables mains-electricity mains-electri city connector cable ( according to local socket type ) CatCart® box with catalyst, and disposal vials containing sodium hydrogen sulfite. Empty product collection vials Hex Keys 2,5 mm, 3,0 mm Wrenches 13 mm, ¼” External source RS232 connector cable Packet of spare Teflon membranes ( 5 pcs ) Set of SS ferrules and nuts 5 pcs ) Connecting SS tube

HPLC pump ( Knauer K-120 ) H-Cube to HPLC pump connector cable ( 9 pin ) Knauer pump Op. Manual ( English&German )

Please ensure that all of the items listed above are present in the delivery package. Check for any visible damage to the H-Cube® components. Should any item be missing or any parts visibly damaged, please please contact your nearest ThalesNano representative. representativ e. For contact details please visit our website: www.thalesnano.com/contact


v. 2. 7.

page:18 of 75

3.2. Unpacking H-Cube® 3.2.1.Upon opening the box, remove the CatCart® holder box, along with the written material, from the top of the foam protective casing.

Figure 11: H-Cube® delivery box

3.2.2. Remove the protective protective foam casing in order order to access the the H-Cube® reactor box and power supply unit.

Figure 12: Unpacking H-Cube®

3.2.3. Carefully remove the H-Cube® and the power supply unit from the delivery box.


v. 2. 7.

page:19 of 75

3.3. Installing

H-Cube®

3.3.1. Place the H-Cube® reactor box inside a fume hood cabinet. 3.3.2. Fill the water water reservoir at the back of the H-Cube® with high-purity dedeionized water. The volume of the water reservoir is an an approx. 150 mL Before filling up the reservoir please remove transportation seal. This label is for transportation only - do not close filling hole during operation of H-Cube® at any time.

Figure 14: Topping up the water reservoir


v. 2. 7.

page:20 of 75

High-purity de-ionized water must be used to fill the water reservoir. Using low quality water can cause irreparable damage to the instrument. Do not impede or block the opening at the top of the water reservoir while the machine is switched on.

3.3.3. Place the water separator line into an open container for the excess water produced from the hydrogen production. The vial used in the picture below has a capacity of 25ml, this being an adequate size to collect the excess water generated from a day’s use.

Empty the excess water container every day before using H-Cube®.

Figure 15: Example excess water container

3.3.4. Connect the reactor box to the power supply unit using the two low-voltage connecting cables supplied. Be careful to connect the two cables correctly: the three-pin one to the three-pin ports on the H-Cube® and power supply, and the four-pin one to the four-pin ports. Ensure to push both connectors into the back of the reactor box until a click is heard. 3.3.5.Connect the mains electricity cable to the back of the power supply unit, and then into the mains power supply. H-Cube® User Manual

v. 2. 7.

page:21 of 75

Figure 16: Connecting the power cables

The electric cables must be guarded against moisture.

3.3.6. Remove the hydrogen exhaust tube from its packaging, and secure one end in the hole on the back of the gas separator. Guide the other end of the exhaust tube into the rear of the fume hood.

Figure 17: Excess hydrogen exhaust tube ( normal accessory )


v. 2. 7.

page:22 of 75

Figure 18: Connecting the excess hydrogen exhaust tube

3.3.7. Remove the stopper plug from both the back pressure valve and from connection:

inlet

Figure 19: the stopper plugs: at inlet (left ) and outlet ( right )

3.3.8. Connect the H-Cube® with 1/16” OD x 0,5 mm ID SS tube to the outlet of the H-Cube®. Connect using the ferrules provided. 3.3.9. Thread the other end of the capillary tube through the guide hole on the left side of the reactor box. 3.3.10.

Secure the capillary tube into the front hole of the gas separator unit.

3.3.11. Thread one end of the longer capillary capillar y tube through a ferrule, and connect it to the inlet valve. Ensure that the capillary tube is pushed as far into the valve port as possible, before tightening the ferrule with a spanner. H-Cube® User Manual

v. 2. 7.

page:23 of 75

3.3.12. Connect the other end of the capillary tube to the HPLC pump bushing outlet. Ensure that the capillary tube is pushed as far into the bushing outlet as possible, before tightening the ferrule. 3.3.13. Connect the Teflon inlet tube to the HPLC pump bushing inlet. Connect the other end of the Teflon inlet tube to the PTFE eluent filter, detached.

Figure 24: HPLC pump prepared for connection to the system

3.3.14. The H-Cube® has two labeled cables supplied with it, an HPLC pump cable and an RS232 external control cable. Take only the HPLC pump cable and connect the H-Cube® and HPLC pump together using the RS232 ports at the rear of both devices. Use the nuts on either end of the connectors to tighten the connectors into place

Figure 25: Connecting the the link cable from the H-Cube® to the HPLC pump

3.3.15.

The H-Cube® is now ready for use.


v. 2. 7.

page:24 of 75

Figure 26: Operational setup


v. 2. 7.

page:25 of 75

4. Operating Instructions Safety instructions: For safety use please follow the instructions as follows:

The H-Cube® generates hydrogen internally. In normal operation, excess hydrogen is released from the sample elution port (on the left-hand side of the H-Cube®, viewed from the front), along with solvent or hydrogenated product. It is essential that adequate precautions are taken to allow this to be safely ventilated by a fume hood cabinet. Under no circumstances should the instrument be opened by anyone other than qualified ThalesNano technicians. Please ensure the water reservoir is topped up at all times. It is vital that the electrolysis cell membrane is kept constantly wet. The cell must not be allowed to run dry or the cell will immediately and irreversibly cease to function. The wetted parts of H-Cube®, HPLC pump and stainless steel parts are susceptible to attack from certain chemicals. Please ensure that the chemicals to be used for the experiment are not in the general known aggressive materials for that that materials. materials. Use of such chemicals may cause malfunction of H-Cube®.


v. 2. 7.

page:26 of 75

4.1. Initiating H-Cube®

During use, the front cover of the unit must be closed down, dow n, the fume hood switched on, and the fume hood door pulled down.

4.1.1. Switch on the H-Cube® by pressing the switch on the back wall of the reactor box. The system will then progress to the startup screen.

Figure 27: The startup screen

4.1.2. Once startup is complete, the device is ready for use and the following screen will be displayed.

Figure 28: System-check screen


v. 2. 7.

page:27 of 75

The H-Cube® will not start to build-up the hydrogen until the start button has been pressed. This ensures that there is no internal hydrogen volume when the device is not in use, unless the option to store the hydrogen from the previous experiment was chosen prior to the last shutdown.

4.1.3. Take out the plastic vial containing the CatCart®, unscrew the lid and remove the CatCart®.

Figure 29: Removing the CatCart® from its vial

4.1.4. Unscrew the cartridge holder cap and place the CatCart® inside the cartdridge holder. Re-screw the holder cap until finger-tight. Wait one minute and then retighten the holder cap.

Figure 30: Placing the CatCart® inside the cartridge holder

If using a longer CatCart® (CatCart®55 or CatCart®70), unscrew the CatCart®holder, screw in the desired new CatCart® holder, re-screw the holder cap until finger-tight, and then close the front cover of the H-Cube®. Note: In order to avoid deformation deformation of connecting tube between holder cap and pressure sensor, modified tube assemblies are available for longer CatCart® types. Please order them with longer holders together.


v. 2. 7.

page:28 of 75

Unscrewing the small CatCart® holder may be difficult. Ensure the small CatCart® holder is regularly applied with grease. See the Maintenance section for details.

If using a longer CatCart® (CatCart®55 or CatCart®70), unscrew the CatCart® holder, screw in the desired new CatCart® holder, re-screw the holder cap until finger-tight, and then close the front cover of the H-Cube®. The way of changing the CatCart® is the same for the longer types as the normal.

Please use a wrench on the middle section of the barrel ba rrel to tighten or unscrew the longer CatCart® holders

4.1.5. Place the inlet tube of the HPLC pump into the solvent reservoir.

Figure 33: Placing the inlet tube into the solvent reservoir


v. 2. 7.

page:29 of 75

4.1.6. Screw the collection vial into place.

Figure 34: Screwing the collection vial into place

4.1.6. Switch on the HPLC pump by flicking the switch on the pump power supply unit. 4.1.7. Set the HPLC pump flow-rate to 1ml/min using the touch-screen interface. Please note that at higher pressures more precise control of the flow rate can be achieved.

Figure 35: Setting the flow rate

4.1.8. Press the Start button on the pump and wait until solvent starts eluting into the product collection vial. This ensures all air is removed from the reaction line and that there are no leaks in the reaction line.


v. 2. 7.

page:30 of 75

The reaction line MUST be clear of Air before use. If the line is not clear of air, the system will have trouble equilibrating when being used in controlled mode.

4.1.9. Set the required pressure and temperature using the touch-screen interface.

Figure 36: Setting the temperature and pressure

4.1.10.

In the display field, select one of the three available hydrogen mode options (Full hydrogen, Controlled hydrogen, no hydrogen) by pressing the Mode button. See the Display Field section on page 8 for a detailed description.

4.1.10.

Press the Start button , the hydrogenation process will now begin. The temperature, pressure, and flow-rate will all rise to the specified levels. If the pressure continues to rise and does not return to the set level, there may be a blockage in the back-pressure valve-consult the Troubleshooting section. The Main screen changes:


v. 2. 7.

page:31 of 75

Figure 37: Main screen ( when starting controllers )

A message will appear in the information field stating the readiness of the system. If the system is still equilibrating to the set pressure value, the message “Stabilizing “Stabilizing the system ” system ” appears, coupled with a beeping sound. When the system has finally equilibrated at the set pressure, the message “System “System stable ” will appear, and the beeping sound will cease. The electrolytic cell will now start to build up to an internal hydrogen pressure to 7 bars above the set inlet pressure. This may take 5-10 minutes, depending on the set pressure, before hydrogen enters the reaction line.

The flow-rate and and pressure settings have all been frozen. The reason for this is to ensure a stable pressure throughout the experiment. The raising of the flow-rate and pressure pres sure will affect this value and the device will have difficultly re-calibrating to the original set pressure value. If you wish to conduct the experiment at a different temperature or pressure, please read Step 5 of the Operating H- Cube® section. section.

4.1.11. Allow the solvent system and hydrogen to flow through the H-Cube® for up to 5 minutes.


v. 2. 7.

page:32 of 75

4.2. Operating H-Cube® Once the system has been flushed, H-Cube® commence.

is now ready for the reaction to

4.2.1. Quickly remove the sample inlet line from the solvent reservoir and place it into the solution of the reactant.

Figure 38: Placing the inlet tube in the reaction solution

Please ensure that the reactant is completely dissolved in the solvent. Any undissolved material will lead to a blocking of the system.

4.2.2. Swap the product collection collection vial for an empty one.

Regularly check the product collection vial. In some reactions the amount of product may be more than the vial can hold, and in this case you will have to replace the full collection vial with an empty one in order to collect the entire reaction product.

4.2.3. Switch back the sample inlet line into the solvent reservoir before the reaction runs dry.


v. 2. 7.

page:33 of 75

Allowing the reaction solution to run dry will cause an air block in the HPLC pump.

4.2.4. Flush the solvent through the system once more for a minimum of 5 minutes. This will reduce the risk of contamination. 4.2.5. To stop the hydrogenation process, you have a choice of two buttons. A stop or a stop & keep H2 option. If you wish to conduct another experiment straight away, press the stop & keep H2 button. button. This will store the hydrogen from the previous experiment, meaning it will take a shorter amount of time than before for the hydrogen to build up to the new pressure value and release into the system. New pressure, flow-rate or temperature parameters may now be selected and the hydrogenation process re-started. Repeat steps 1-5 until the experimental session is finished.

Figure 39: Main screen, keep hydrogen option

If you wish to discontinue using the H-Cube® for a set period then press the Stop button. button. The hydrogen generated from the previous experiment will be released through the water outlet tube at the rear of the device. A new screen will w ill appear. The release of hydrogen may cause a loud hissing noise, do not be alarmed. The heating of the system will also cease and the system will w ill start to cool down.


v. 2. 7.

page:34 of 75

Figure 40: Hydrogen release screen

During use, the catalyst column may become hot, particularly when performing high temperature reactions. Wait until it cools down before taking it apart, in order to avoid possible injury from burning.

4.2.6. Unscrew the cartridge holder, remove the CatCart®, place it in the catayst deactivating solution, then seal the vial.

Figure 41: Placing the CatCart® in solution The handling of hydrogen-saturated pyrophoric catalysts generates certain safety concerns. To deactivate the catalyst cartridge, place it in the catalyst poisoning solution of aqueous sodium hydrogen sulfite provided by ThalesNano.

4.2.7. Work-up the collected reaction mixture as desired.


v. 2. 7.

page:35 of 75

4.3. Shutting-down H-Cube® Shut down H-Cube® after each day’s usage in order to reduce the internal pressure of the device to zero. The remaining hydrogen will come out through the open valve beside the product collection vial, and will be removed by the fume hood.

4.3.1. Press the shutdown button button on the touch-screen interface. 4.3.2. The prompt

“ Shutdown: Are you sure? “ appears on the screen. Press Yes .

Figure 42: Shutdown prompt screen


v. 2. 7.

page:36 of 75

4.3.2. The message

“ Shutting down, please wait… “ appears on the screen. Wait for roughly 1 minute while the shutdown is executed.

Figure 43: Shutdown in progress screen

The H-Cube® will perform various procedures to make the machine safe for storage. One such step is the evacuation of hydrogen from the water outlet tube at the rear of the device. This may cause a loud hissing noise, do not be alarmed, as this is normal. 4.3.3. The message

“ You can turn off the th e instrument. “ appears on the screen. Switch off the H-Cube® at the back of the reactor box.

Figure 44: Closing shutdown screen


v. 2. 7.

page:37 of 75

5. Examples for Hydrogenation Protocols 5.1. Self-test Procedure There are two chemicals provided with the H-Cube® that can be used to check if the system is functioning to its full potential: potential:

•

a nitro group reduction of 5-nitroindole O2N

H2N N H

•

N H

an N-benzyl de-protection of 4-anilino-1-benzylpiperidine 4-anilino-1-benz ylpiperidine

Ph N H

N

N H

NH

The tests to ascertain the performance of the H-Cube® should be performed as follows:

5.2. Nitro Reduction 5.2.1. Follow Steps 1 to 13 of the Initiating H-Cube® section, section, selecting the Full hydrogen option (step 10), using ethanol as the solvent, and setting the temperature and pressure to 30°C and 1 bar respectively. Use a 10% Pd/C catalyst. 5.2.2.

Dissolve 81mg (0.5mmoles) of 5-nitroindole and dissolve in 10ml of ethanol (96% or above is adequate) to produce a yellow solution.

5.2.3.

Remove the sample inlet line from the solvent reservoir, and place it into the nitroindole solution.


v. 2. 7.

page:38 of 75

Figure 45: Placing the inlet tube in the nitroindole solution

Ensure that the reactant is completely dissolved in the solvent. Any undissolved material will lead to a blocking of the system.

5.2.4. Swap the product collection collection vial for an empty one.

If the reaction is progressing efficiently, the collected reagent solution should be colorless. Regularly check the product collection vial. In some reactions the amount of product may be more than the vial can hold, and in this case you will have to replace the full collection vial with an empty one in order to collect the entire reaction product. Do not allow the reaction solution to run dry, as this will cause an air block in the HPLC pump.

5.2.5.

Once the nitroindole solution is almost empty, remove the sample inlet tube from the reaction solution, and place it back into the solvent reservoir.

5.2.6.

Flush the solvent through the system once more for 5 minutes. This will reduce the chances of contamination.

5.2.7.

Stop the hydrogenation process by pressing the stop button button on the touchscreen interface.

5.2.8.

Reduce the temperature and pressure to room temperature and 1 bar, respectively.


v. 2. 7.

page:39 of 75

Ensure that the pressure has returned to the minimum level of 1 bar, before proceeding to the next steps.

5.2.9.

Unscrew the cartridge holder cap, remove the CatCart® and place it in the catayst deactivating solution. The handling of hydrogen-saturated pyrophoric catalysts generates certain safety concerns. To deactivate the catalyst cartridge, place it in the catalyst poisoning solution of aqueous sodium hydrogen sulfite provided by ThalesNano. Used cartridges may be sent back to ThalesNano.

5.2.10. Take a TLC sample from the product collection vial and run it using an eluent of 10% methanol in dichloromethane. The TLC should look like the following: Product

Starting Material

Figure 46: Nitroindole TLC

If your TLC does not look like the given example, retry the experiment ensuring you have followed all steps exactly. If there is still no reaction then contact your nearest ThalesNano representative.


v. 2. 7.

page:40 of 75

5.3. N-benzyl De-protection of 4-anilino-1-benzylpiperidine Follow steps 1 to 10 from the 5-nitroindole example above, but using: •

• •

A dissolved solution of 4-anilino-1-benzylpiperidine 4-anilino-1-benzyl piperidine (133mg, 0.5mmoles) in 20ml ethanol A set temperature of 60° 60°C, and a pressure of 1 bar. Use a 10% Pd/C catalyst

During use, the catalyst column may become hot. Wait until it cools down before taking it apart, in order to avoid possible injury from burning.

The TLC, using an eluent of 10% methanol in dichloromethane, should look like the following:

Product

Starting Material Figure 47: De-benzylation TLC


v. 2. 7.

page:41 of 75

5.4. A Starters Starters guide to what parameters can can be used when reducing various functional groups The following list is just a guide and a useful starting point. The actual conditions to produce 100% product in one run may vary depending depe nding on the compound being reacted. Please read the optimization section below for more details on how to optimize conditions to achieve 100% conversion.

1. Simple alkenes, alkynes, nitro reduction: Full hydrogen mode, room temperature, 10% Pd/C or Raney Ni. Ni.

2. Cbz, N-, and O-Benzyl protected hydrogenolysis: hydrogenolysi s: Full hydrogen mode, 50ºC and above, 10% 10 % Pd/C or Pd(OH)2/C. Acetic acid can be used, in varying dilutions, to aid deprotection of benzyl groups.

3. Nitrile, imine, and oxime reduction reduction:: 50 bar pressure and 50ºC and upwards.

4. Aromatic heterocycles, sterically hindered or highly substituted alkenes, phenyl groups: 80 bar and 80ºC and upwards. PtO2, Raney Ni, Pd(OH)2/C. Acetic acid can be used, in varying dilutions, to aid reduction of the aromatic heterocyclic ring. Acetic acid acid must not be used with Raney Ni.

Some difficult reductions will require longer CatCarts® to complete the reduction in one run. These Thes e include difficult debenzylations, aromatic heterocycles, sterically hindered or highly substituted alkenes, phenyl groups.


v. 2. 7.

page:42 of 75

6. Advanced Use 6.1. Optimization of of Reaction Conditions for Enhanced Product Conversion Once you have become accustomed to performing reactions on the H-Cube® system, both at high pressure and at atmospheric pressure, it is time to introduce how to use the system to optimize reactions. This section is especially useful for chemists who are faced with a reactant or reduction they have never used or performed before, and who are unaware of what the best conditions are to achieve high yield and product conversion. The following steps describe the process you should follow in order to achieve the best possible results. 1. Start with a flow rate of 1ml/min and a concentration of 0.05M. These conditions are fairly standard and are used routinely at ThalesNano for reductions using one CatCart®30. 2. If available, look up reaction conditions for the type of catalyst used, the ideal temperature and pressure for the reaction, and begin the reaction at these parameter values. 3. If reaction conditions are not available, start the reaction at room temperature and atmospheric pressure. Use a 10% Pd/C catalyst, as this is capable of reducing most functional groups. 4. Analyze the reaction using LC or LCMS, and note the product conversion. If product formation is not visible, or is low, the temperature of the reaction should be raised by 10˚C increments until total or high conversion is be achieved.

If when raising the temperature, side products or decomposition are noted, return to a temperature where there is little or no decomposition.

5. If 100% reduction of the starting material has still not been accomplished, set the H-Cube® to the temperature that produced the highest product conversion without any side products or decomposition. Raise the pressure by one increment and note the conversion. 6. If product conversion is still not 100% or an acceptable level, then continue to raise the pressure, and note conversion using the steps laid out in the Conducting high pressure reactions section.


v. 2. 7.

page:43 of 75

7. If product conversion is still not 100%, repeat the above steps using a longer column. This will ensure an adequate residence time on the catalyst to achieve complete conversion. If still incomplete try a different catalyst or a slower flowrate.

6.2. Further Reaction Conditions for Enhanced Product Product Conversion Acetic acid is useful in increasing the rate of the reaction, particularly in reduction of heterocycles or de-benzylation reactions. It is useful to try using one or two equivalents with the above protocol, as this may reduce the temperature and pressure parameters of the reaction significantly. The solvent used to wash the catalyst can have an impact on the rate of the reaction. For debenzylation reactions, washing the catalyst with cyclohexane can increase the initial rate ahead of using an alcohol solvent. If the above method and reaction conditions fail to produce 100% product conversion in one run through the machine, the reaction mixture can be recycled. This process is described in the following section.

6.3. Recycling the Reaction Mixture Recycling of the reaction mixture back into the H-Cube® until total product conversion can be achieved via one of the two following methods: Method 1:

1. Before the starting material vial has has emptied, replace the production vial for an an empty one, pour the full production vial back into the starting material vial. and continue the reaction. 2. Wait until the collection vial is full, and re-analyze the results. If the results still show incomplete conversion, repeat step 1.


v. 2. 7.

page:44 of 75

Method 2:

This method is most useful for difficult reductions that take a lot of cycles through the machine. This method involves detaching the vial from the gas separator while the machine is in use. This will result in hydrogen being generated out of the vial, and into the atmosphere of the fume hood. This step is performed at the operator’s own ow n risk.

1. When the starting material vial is just about empty, stop the H-Cube® and the HPLC pump. 2. Unscrew the full product product vial and place in a holder. 3. Unscrew the reaction line capillary tube from the top of the gas separator separator and place in the product vial. 4. Place the Teflon sample inlet tube into the product vial. 5. Hold the two lines in place using parafilm, ensuring that there is enough enough space for the release of the excess hydrogen.

Figure 48: Placing parafilm over the product vial

6. Restart the HPLC pump and then the H-Cube®, at the original settings.


v. 2. 7.

page:45 of 75

7. Troubleshooting 7.1. Touch-screen Touch-screen Interface Error Messages Error Message Generator Cell Error

Possible Cause No water in the water reservoir.

Voltage on cell exceeds the limit. Electrical defect in the H-Cube®. Water Flow Error

No water in the water reservoir.

Blockage in the system. Water leak in the system. Defect in the water pump. Valves Error Hydrogen leak No link with pump


Mechanical defect in one or more of the valves. Cell leak or loose internal connection. The H-Cube® is not correctly connected to the HPLC pump.

v. 2. 7.

Corrective Action Check the water level in the water reservoir. Refill if necessary. Switch H-Cube® off, call for service. Switch H-Cube® off, call for service. Check the water level in the water reservoir. Refill if necessary. Switch H-Cube® off, call for service. Switch H-Cube® off, call for service. Switch H-Cube® off, call for service. Switch H-Cube® off, call for service. Switch H-Cube® off, call for service. Check the RS232 cable linking the H-Cube® to the HPLC pump. Make sure it is properly connected.

page:46 of 75

7.2. Problems in the H-Cube® System Problem The system pressure rises above 100 bars when the pump is started and without raising the pressure level(without returning back to the originally set value after a few seconds) Leak in the CatCart® column

Solvent not passing through the system

The system pressure is decreasing from the set value back to 1 bar without stopping the H-Cube®. Solvent is leaking from the bubble detector. There is little or no hydrogen being produced on full hydrogen mode

Possible Cause There may be a blockage in the back pressure valve.

There may be a defect in the back pressure valve.

Corrective Action Change the Teflon membrane (see Maintenance section section for details) Switch H-Cube® off, call for service.

The CatCart® may be faulty, or may be screwed into the catalyst holder either unevenly or too tightly.

Replace the CatCart® for a new one.

There may be air in the HPLC pump.

Check for air bubbles in the capillary inlet tube. Drain any air from the tube using a syringe.

The titanium inlet frit may be blocked

First try flushing the frit with solvent. If unsuccessful, change the frit for a new one.

The HPLC pump may be faulty.

Contact the pump manufacturer.

The inlet frit may be blocked (shown by a large pressure increase of the inlet pressure value when started) There may be a leak in the PEEK tubing passing through the bubble detector. The check-valve may be stuck.

First try flushing the frit with solvent. If unsuccessful, change the frit for a new one. Replace the reaction line line tube. See the General Maintenance section below. Try running an experiment at 50 bar and then revert back to 1 bar full hydrogen mode and see if the hydrogen production has improved. If not, replace the check-valve using the procedure outlined in the Maintenance section.

If you are experiencing problems with the H-Cube® and a service engineer is required, please e-mail a short description of the problem, along with your contact details, to the following address: [email protected].. [email protected] We will respond within 24 hours.


v. 2. 7.

page:47 of 75

8.Solvent Resistance

The following are solvents which are NOT recommended for use with the H-Cube®. The H-Cube® includes stainless steel parts. Solvents which corrode stainless steel should NOT be used, for example, concentrated halogenated acids!

Aqua regia Bromine/dibromoethane Bromine (dry) Bromine (wet) Chlorine (liquid) Hydrobromic acid Hydrofluoric Acid Nitric acid Phenol Sulphuric acid Hydrochloric Hydrochloric acid


v. 2. 7.

page:48 of 75

9. Detecting a blockage in the H-Cube® There are a number of ways of detecting if a blockage has occurred and where the blockage is located. The most common places for a potential blockage is either in the back-pressure valve, CatCart® heater and holder, or the H 2 /Substrate /Substrate mixer.

Bubble Detector

Pressure Detector

CatCart ® Holder

Backpressure valve

H2 /Substrate Mixer

CatCart® Heater

Figure 49: Front plate


v. 2. 7.

page:49 of 75

9.1. A blockage in the back-pressure regulator A blockage in the back-pressure valve is easy to detect. If running an experiment when the pressure is set to zero, the pressure reading in the pressure regulator control field on the main touch screen should read zero. If the reading is greater than five (in Figure 50 below, the reading is 62), the teflon membrane in the back pressure valve should be cleaned and replaced. If the back pressure is completely blocked, the bar indicated below, will continue to rise until it reaches over 100 bar.

If this occurs, please “Stop” the pump and the reaction immediately.and clean the valve. This action should solve the problem. If not please contact your supplier for help. Please refer to the Maintenance section below for details.

If there is a blockage, a bar will appear here and the value will be higher than the set level

Figure 50: A blockage in the back-pressure valve.

9.2. A blockage in the reaction reaction line before the back-pressure back-pressure regulator If there is a blockage in the reaction line before the back pressure valve, the value in the HPLC pump control field on the main touch screen, see Figure 51, will continue to rise to a value significantly above the pressure regulator value. If this occurs please stop the pump immediately and stop the reaction. H-Cube® User Manual

v. 2. 7.

page:50 of 75

The location of the blockage can be located in NoH2 mode by performing the following: Disconnect the SS tube at the left connecting point of the Bubble Detector unit. Start the pump again. If the pressure continues to rise in the HPLC pump field there is still a blockage and it occurs before the CatCart® system. If the pressure does not rise once the pump has been restarted, the blockage can be attributed to the CatCart® and heater section. Remove the CatCart® and clean inside the CatCart® holder and screw cap. Insert a new CatCart® and try the pump again. If the pressure continues to rise, please contact the service department. Try disconnecting the SS tube leading into the hydrogen/substrate mixer. Start the pump. If the pressure doesn’t rise, then the blockage can be attributed to the hydrogen/substrate mixer. Take the mixer apart, this process is described in maintenance section, and clean or replace the titanium frit. Replace the fittings and try the pump again. There should now be no pressure rise and the system can now be used. If there is still a blockage and you can’t remove it then please contact the service department. This value will continue to rise once the pump has started

This value will not be affected

Figure 51: A blockage in the reaction line before the back-pressure valve

A one of the most likely reasons for a blockage in the reaction line before the backpressure valve is blockage in the CatCarts®. Pressure increase in the CatCart® depends on : * type of filling of CatCarts® * flow rate * mode of Hydrogenation * previous use * standby period of CatCart® before using.


v. 2. 7.

page:51 of 75

Generally speaking, for information: A normally less than 15 bar increase is acceptable for a 30 mm type, at 1 mL /min flow rate CatCart® in Controlled mode. An approx. 20 bar is the limit for Full H2 mode since in the Full H2 mode the pressure increase is generally higher than in Controlled mode. The pressure increase must not increasing continuously. continuousl y. Pressure increase may be higher if the CatCart® is reused, or wetted and not used for long period (days or a long weekend) If the pressureincrease ( i.e. the pressure difference between inlet and system ) exceeds more than that mentioned above the CatCart® must be replaced.


v. 2. 7.

page:52 of 75

10. Maintenance Opening of the H-Cube® reactor box, and any necessary repairs can only be performed by ThalesNano service experts. Unauthorized opening ofthe device will render the warranty null and void.

10.1. Daily Maintenance Checks 1. Check the electrical connections to ensure that everything is connected correctly and guarded against moisture. 2. Check the water level every day before starting work. Refill with de-ionized de-ionized water when necessary. 3. Ensure that the the system is free from impurities by flushing solvent through before a reaction.

10.2. General Maintenance 10.2.1. Changing the Teflon membrane in system valve 1. Remove the ferrules from the back pressure valve using wrench (provided). Than using using a 3mm Hexagonal key, remove the two screws that hold the valve head in place.

Figure 52: Removing the back pressure valve head screws


v. 2. 7.

page:53 of 75

2. Remove the valve head; use a Stanley knife to carefully carefull y prize the Teflon membrane away from the valve. Take care not to scratch the stainless steel valve surface. Using tweezers, remove the Teflon membrane from the valve.

Figure 53: Removing the Teflon membrane

Replace the Teflon membrane with a new one, and replace the valve head, with the two screws in place.

Figure 54: Replacing the new Teflon membrane

3. Tighten the two valve head screws by screwing them alternately into place place with the 3mm Hex key, using equal torque for both screws, and reconnect the SS tube ferrules. Align the center line of the SS tube and ferrule to the center of thread carefully and tighten the SS ferrule by finger first ( 4 to 6 turns ), then tighten the ferrules using a wrench to achieve proper sealing.


v. 2. 7.

page:54 of 75

Figure 55: Tightening the back pressure valve head and connectors into place

10.2.2. Clearing air from the HPLC pump head 1. Switch off the HPLC pump. 2. Disconnect the SS tube from the pump outlet port, and attach the syringe shipped with H-Cube® using the white fingertight connector. Make sure there is no leakage at connection. 3. Start the pump at small flow rate ( 1 mL/min or so ), and drain the air out of the pump by retracting the syringe. A flow of solvent should now be seen inside the syringe.

Figure 56: Draining air from the HPLC pump


v. 2. 7.

page:55 of 75

4. Switch the pump off. Unscrew the fingertight with the syringe. Switch the pump on again and make sure that the drops are continuous. Increase the flow rate to 3 mL/min using the touch screen for 1 minute. If the drops are continuous and constant, return the flow rate to 1 mL/min. 5. Reconnect H-Cube® inlet tube to the pump outlet. 6. Start the pump and wait until the drops appear at product collector end. Note: make sure that there is CatCart® placed in the holder !

10.2.3. Cleaning or replacing the Inlet frit 1. Remove the connectors from the mixing unit. Using a 3mm Hex key, remove the two screws that hold the mixing unit in place. Method same as with the backpressure valve. 2. Using a Stanley knife or scalpel, please work the titanium frit out of it’s position. 3. Place the frit in a solvent solution, e.g. methanol, and sonicate for 5-10 minutes. Please clean any chemical residue which can be seen on the mixer head and inside the mixer itself using ethanol or methanol. 4. Re-insert the frit using your finger. Ensure that the smoothest surface of the titanium frit is facing towards you when it is placed into position.

5. Place the front unit back into position and, and, while holding the front unit in place, screw the original screws back into position. Tighten with the Allen key.

6. If problems with blocking persist, please contact the service department.

10.2.4. Cleaning the Inlet-line filter or the PTFE eluent filter The inlet-line filter or PTFE eluent filter can be cleaned by placing in a vial full of methanol and sonicating for 10 minutes.


v. 2. 7.

page:56 of 75

10.2.5. Changing the check-valve 1. First unscrew the short connection tube between check-valve body and and connector, holding the check-valve holder by 13 mm wrench. 2. Unscrew the check-valve holder and remove it from the face of the H-Cube®.

Figure 57: Removing the connections and check-valve holder

3. Carefully Carefull y remove the check-valve from the cavity using tweezers. 4. Replace the new check-valve into the check-valve holder. 5. The check-valve has a white head with 2 horizontal lines nearest this head. When replacing the check-valve please ensure that the end with the white head is facing the H-Cube®, as shown in the figure below.

Replacing the check-valve in the wrong direction will result in solvent leaking into the H-Cube®. Please ensure check-valve is placed in the right direction.

Figure 58: Inserting check-valve, with the the horizontal line furthest away from you into the check-valve holder.

6. Insert the check-valve holder containing the check-valve back and screw back into position using your fingers. Using the spanner provided, tighten the fitting to ensure there is no leak ( make sure not to overtighten the valve holder).


v. 2. 7.

page:57 of 75

10.2.6. Piston backflushing Piston backflushing removes traces of salt and other decontaminates from the backside of the pistons of the HPLC pump. If you use saline solvents or buffer solution we highly recommend that you continuously backflush in order to prevent crystallization which can damage your piston seals. Please follow the steps bellow: 1. Push a 1/16 ID tube onto both flushing opening, see Piston backflushing capillaries

Figure 59: Pump head

2. Place the low end of the tubing in a flask. 3. Fill the syringe with rinsing liquid. 4. Connect the syringe with the tubing. 5. Press liquid through the pump head, until it flows without any air bubbles into the container. 6. Remove tubings from flush opening. We recommend connecting both flush openings with a tubing to prevent vaporization of solvents and drying out of the piston chamber. If you want operation with continuous backflushing you can attach two containers of rinsing liquid instead of the priming syringe. The containers should be positioned that one container is located higher than the other, thus ensuring liquid flow through the pump head without any assistance.

10.2.7. Useful hints: 9.2.6.1. Even normal the use of CatCart® and H-Cube® may cause corrosion and chemical coating on surface the CatCart® holder threads. This may increase friction during tightening of cap of holder. The consequence is reduced torque H-Cube® User Manual

v. 2. 7.

page:58 of 75

applied on the CatCart® sealing. That’s why it is recommended to apply frequently, depending on the amount of use. Use a very small amount of grease on the surface of the outer thread of the CatCart® holder. Recommended grease is a kind of high viscosity type grease ( like vacuum grease ). Applying a small amount of grease a.) Using your fingers, unscrew the small CatCart® holder from the heater unit. a. Apply a small film of vacuum grease to the threads at both ends of the CatCart® holder.

Figure 60: Application of grease to the thread of the CatCart® holder

This should be done frequently to prevent the CatCart® holder from seizing in the heater block.

9.2.6.2. Another useful hint is to apply a “ double action “ tightening process for the CatCart® holder assembly. After the tightening of CatCart® holder, the plastic seal at the two ends of CatCarts® relaxes and the effectiveness of sealing becomes worse. It’s recommended to apply a second but same tightening action with the same method and same torque using your finger again two minutes after the first tightening. It can definitely improve reliability reliabil ity in the sealing of the CatCart®’s CatCart®’ s connections.

11. Necessary Servicing


v. 2. 7.

page:59 of 75

Opening of the H-Cube® reactor box, and any necessary necessar y repairs can only be done by ThalesNano service experts. Unauthorized opening of the device will render render the warranty null and void.

If the H-Cube has not been used for a period of weeks, then the user must perform the following before performing a reaction: •

• •

The pump pump is completely clear of air. Please use the above instructions instructio ns and flush the system with solvent (methanol) for 10 minutes. The system can operate at at Full H2 mode. Check that H 2 gas is produced. The system can operate at 100 bar on No H2 mode. Check for solvent leaks.

12. Replacement Parts All replacement parts are available from ThalesNano. Please go to the www.thalesnano.com official website to consult our accessories catalogue and order them on-line.

13. Accessories ThalesNano recommends the following accessories to be used with the H-Cube®. All accessories have been designed or tested for complete compatibility with all functions of the system. The following replacement accessories can be purchased from us or directly from the distributor. Please consult our accessories catalogue.

HPLC Pump The following recommended HPLC pump can be ordered directly from Knauer, or through ThalesNano.

Knauer WellChrom WellC hrom HPLC-pump K-120: H-Cube® User Manual

v. 2. 7.

Order Number: A41501 page:60 of 75

www.knauer.net HPLC Pump from ThalesNano

Order Number: THS 09000

14. Technical echnic al Data Hydrogenation Process

Pressure Range of H-Cube®: Reaction Temperature Range: Flow Rates: Optimal Flow Rates: Maximum Hydrogen Production Rate: Required Water Specifications: System Specifications Dimensions of H-Cube®:

From 1 bar to a maximum of 100 bars From room temperature to 100°C 100°C 0.1 - 3 ml/min 0.5 - 2 ml/min 30 cm 3 /min in Full Full Hydrogen Mode De-ionized water with recommended conductivity of 14 M Ώ * cm Height: 29 cm (11.4”) (including touch screen) Width: 26 cm (10.2”) Depth: 44 cm (17.3”)

Weight of H-Cube®: Power requirements:

12 kg (27 lbs) Mains: 100V to 240V AC , 47- 63Hz Automatically adjusted:

Water Reservoir Capacity:

150 ml

Interfaces Touch-screen:

Width: 120mm (4.72") Height: 89mm (3.5”)

Accessories For optimal results using the H-Cube®, we recommend you use the following standard HPLC accessories or their equivalent:

HPLC pump:

KNAUER WellChrom HPLC-pump K-120*

Tubing:

Stainless Steel tubing, Outer diameter: 1/16” Inner diameter: 0,5 mm

Connection size: ( for inlet and outlet connections )

10-32 UNF

* for more Technical specifications regarding HPLC-pump and its operating instructions see attached KNAUER Operating manual


v. 2. 7.

page:61 of 75

( available in English and German)

15. Warranty Information The H-Cube® is delivered in accordance with ThalesNano standard terms and conditions, a copy of which is attached to the purchase invoice and is also available on request. The guarantee period of H-Cube® is 12 months, starting from the date of delivery to the client. Operation inconsistent with the manufacturer’s instructions is excluded from the warranty, while the unauthorized opening of the device will render the warranty null and void. Only CatCarts® supplied by ThalesNano can be used with the H-Cube® unless otherwise expressed by ThalesNano. The use of any other catalyst system other than that provided by ThalesNano will render the warranty null and void. ThalesNano Nanotechnology, Inc.

H-1031 Budapest Graphisoft Park Záhony u 7 Hungary Tel: +36 1 8808 500 Fax: +36 1 8808 501 E-mail: [email protected] Web: www.thalesnano.com

If we find a defect covered by the warranty, repair, or replacement, at our discretion, will be carried out free of charge. Packing and transport costs are borne by the customer.


v. 2. 7.

page:62 of 75

16. Appendices Appendix 1: The service window – an explanation

Pressures: H2 gen.: Inlet: System:

(in bars) Set: Inlet + 7 bars when in running state, otherwise 0 Act: Actual H2 pressure when in running state Act: The actual inlet pressure Set: The pressure set by the user Act: The actual, measured pressure value

Valves:

Values between 0020 (valve open) and 1000 (valve closed). (±3) Set: The value set by the user Act: The actual, measured value

Temperature:

Set: The temperature set by the user (in °C) Act: The actual, actual , measured temperature tem perature (in °C) °C) The actual voltage of the cell (in tenths of a volt) e.g. 0026 = 2.6 V Bubble detector: Proportion of gas to liquid. E.g. 007 = 7% gas, 93% liquid Notice: In Full Hydrogen mode “N/A” value appears in the bubble detector window because control of the hydrogen is not necessary in Full Hydrogen mode.

H2 cell: Bubble d.


v. 2. 7.

page:63 of 75

Appendix 2: Control of the the H-Cube® from an external source 1. General

The serial interface at the rear of the instrument, ( see No. 17, Figure 4 on page 8), allows control of the H-Cube® from an external computer via a link cable. Simple ASCII codes are able to control the H-Cube®. ESC sequences are not needed. Thus, a simple terminal program may be used. The specifications for data transfer are: 9600 8 1 no

baud bit stop bit parity check

The general command format: CommandLabel - two characters, (capital) for example : VS Param1 - numeric parameter, with decimal digits. Direction - '=', '?' to specify the Get or Set command. Param2 - numeric parameter, with decimal digits. - ASCII 13 code character If Param1 and Param2 are both set, then their maximum size can be 1 byte (0-255). When only one parameter is set, then its max size can be 2 bytes (0-65535). The general result format: 'OK' ?- After a successful command transfer, there is no resulting data. - After a successful command transfer, resulting data will be displayed. - Some error occurred. H-Cube® User Manual v. 2. 7. page:64 of 75 2. List of errors 1. Invalid command - ?1 ----------------------Invalid, unknown command. 2. Invalid parameter - ?2 ------------------------The command has an invalid parameter value. Most frequently it marks a range error. 3. Invalid state - ?3 --------------------The command cannot be performed in the current state. The available states of the command described in the RS232-command-reference.txt. 4. Communication error - ?41, ?42 --------------------------------Internal communication error. 5. Other error - ?5 --------------------------Undefined malfunction. H-Cube® User Manual v. 2. 7. page:65 of 75 3. RS232 command documentation documentation - quick reference Software version: 2. 5. 0. 6 The valve commands : VS - Get the system valve position ............... [VS?] VH - Get the hydrogen valve position ............. [VH?] VW - Get the water separator valve position ...... [VW?] --> --> --> The pressure commands : PS PS PI PH - Get Set Get Get the the the the system pressure .................... . system pressure .................... . inlet pressure ..................... . hydrogen pressure ................... [PS?] [PS=] [PI?] [PH?] --> --> --> --> The temperature commands : TC - Get the column temperature .................. [TC?] TC - Set the column temperature .................. [TC=] --> --> OK The HPLC pump commands : PF PF PE PE - Get Set Get Set the the the the HPLC HPLC HPLC HPLC pump pump pump pump flow rate ................. flow rate ................. motor state ............... motor state ............... [PF?] [PF=] [PE?] [PE=] --> --> --> --> OK OK The gas/liquid ratio command : GL - Get the gas/liquid rate .................... . [GL?] --> The hydrogen mode : HM - Get the hydrogen mode ...................... . [HM?] HM - Set the hydrogen mode ...................... . [HM=] --> --> OK The touch commands : BC - Execute the command ........................ . [BC=] BE - Get the command state ...................... . [BE?] --> OK --> The function commands : FE - Get the function state ..................... . [FE?] FS - Get the function step ...................... . [FS?] --> --> The parameter readers : GP - Get the system parameter value .............. [GP?] H-Cube® User Manual v. 2. 7. --> page:66 of 75 4. List of commands The following are the list of commands which can be controlled by external software. The valve commands : VS - Get the system valve position VS? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Selector Parameter #2 : Results : Valve position (20 - 1000) State : No constraint. Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value VH - Get the hydrogen valve position VH? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Selector Parameter #2 : Results : Valve position (20 - 1000) State : No constraint. Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value VW - Get the water separator valve position VW? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Selector Parameter #2 : Results : Valve position (20 - 1000) State : No constraint. Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value The pressure commands : PS - Get the system pressure PS? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Selector Parameter #2 : Results : The pressure value in bar (0 - ?) State : No constraint. H-Cube® User Manual v. 2. 7. page:67 of 75 Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value PS - Set the system pressure PS= --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : The pressure value in bar (0 - 100) Results : Always 0 State : Available in 'Ready' state. PI - Get the inlet pressure PI? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : Results : The pressure value in bar (0 - ?) State : No constraint. PH - Get the hydrogen pressure PH? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Selector Parameter #2 : Results : The pressure value in bar (0 - ?) State : No constraint. Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value The temperature commands : TC - Get the column temperature TC? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Selector Parameter #2 : Results Result s : The temperature temperat ure value in °C (0 - ?) State : No constraint. Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value TC - Set the column temperature TC= --> OK --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter Paramete r #2 : The temperature tempera ture value val ue in °C (0 - 100) Results :State : Available in 'Ready' state. H-Cube® User Manual v. 2. 7. page:68 of 75 The HPLC pump commands : PF - Get the HPLC pump flow rate PF? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : Results : The flow rate value in microliter/min (0 - ?) State : No constraint. PF - Set the HPLC pump flow rate PF= --> OK --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : The flow rate value in microliter/min (0 - 3000) Results :State : Available in 'Ready' state. PE - Get the HPLC pump motor state PE? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : Results : The motor state value State : No constraint. Available values for the result 0 : The motor is disabled 1 : The motor is enabled PE - Set the HPLC pump motor state PE= --> OK --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : The motor state value Results :State : Available in 'Ready' state. Available values for the parameter #2 0 : Disable motor 1 : Enable motor The gas/liquid ratio commands : GL - Get the gas/liquid rate GL? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : Results : The gas/liquid ratio value (0 - 100) State : No constraint. Available values for the parameter #1 0 : The actual (measured) value 1 : The adjusted value H-Cube® User Manual v. 2. 7. page:69 of 75 The hydrogen mode : HM - Get the hydrogen mode HM? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : Results : The hydrogen mode State : No constraint. Available values for the result 00 - Controlled by HCUBE 01 - Full hydrogen mode 02 - No hydrogen HM - Set the hydrogen mode HM= --> OK --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : The hydrogen mode Results :State : Available in 'Ready' state. Available values for the parameter #2 00 - Controlled by HCUBE 01 - Full hydrogen mode 02 - No hydrogen The touch commands : BC - Simulate the touch command BC= --> OK --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : Parameter #2 : The command code. Results :State : No constraint. Available values for the parameter #2 00 - Start the hydrogenation 01 - Stop and release the hydrogen pressure 02 - Stop and keep the hydrogen pressure 03 - Switch to the service screen 04 - Cancel the service screen, switch to the previous screen 05 - Purge water separator 06 - Shut down the instrument 07 - Increase the column temperature 08 - Decrease the column temperature t emperature 09 - Increase the column temperature (in running mode) 10 - Decrease the column temperature t emperature (in running mode) 11 - Increase the system pressure 12 - Decrease the system pressure 13 - Increase the HPLC pump flow rate 14 - Decrease the HPLC pump flow rate 15 - Switch the hydrogen mode H-Cube® User Manual v. 2. 7. page:70 of 75 16 - 'Yes' button in the shutdown yes/no dialog 17 - 'No' button in the shutdown yes/no dialog 18 - 'OK' button in water flow error dialog 19 - 'OK' button in pressure error dialog 20 - 'OK' button in water level error dialog 21 - 'OK' button in HPLC pump error dialog BE - Get the touch command enabled state BE? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : The command code. Parameter #2 : Results : The enable state of the touch command State : No constraint. Available values for the result 0 : The touch command is disabled. 1 : The touch command is enabled. Available values for the parameter #1 00 - Start the hydrogenation 01 - Stop and release the hydrogen pressure 02 - Stop and keep the hydrogen pressure 03 - Switch to the service screen 04 - Cancel the service screen, switch to the previous screen 05 - Purge water separator 06 - Shut down the instrument 07 - Increase the column temperature 08 - Decrease the column temperature t emperature 09 - Increase the column temperature (in running mode) 10 - Decrease the column temperature t emperature (in running mode) 11 - Increase the system pressure 12 - Decrease the system pressure 13 - Increase the HPLC pump flow rate 14 - Decrease the HPLC pump flow rate 15 - Switch the hydrogen mode 16 - 'Yes' button in the shutdown yes/no dialog 17 - 'No' button in the shutdown yes/no dialog 18 - 'OK' button in water flow error dialog 19 - 'OK' button in pressure error dialog 20 - 'OK' button in water level error dialog 21 - 'OK' button in HPLC pump error dialog The function commands : FE - Get the function enabled state FE? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : The function code. c ode. Parameter #2 : Results : The enabled state of the function State : No constraint. Available values for the result 0 : The function is disabled. 1 : The function is enabled. H-Cube® User Manual v. 2. 7. page:71 of 75 Available values for the parameter #1 00 - The startup sequence controller f unction 01 - The start sequence controller function 02 - The stop sequence controller function 03 - The shutdown sequence controller function 04 - The H2 emptying sequence controller function 05 - The H2 generator control function 06 - The H2 valve control function 07 - The water pump control function 08 - The system valve control c ontrol function 09 - The HPLC pump monitor function 10 - The bubble detector monitor function 11 - The water level detector function FS - Get the function step FS? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : The function code. c ode. Parameter #2 : Results : The actual step of the function if it is running, or the last step. State : No constraint. Available values for the parameter #1 00 - The startup sequence controller f unction Available result values : 0 - Initializing.. 1 - Setting valves.. 2 - Setting valves.. 301 - The start sequence controller function Available result values : 0 - Initializing.. 1 - Close H2 valve.. 2 - Starting HPLC pump.. 3 - Waiting for user.. 4 - Change screen.. 5 - Starting controllers.. 6 - Building pressures.. 7 - Setting H2 valve.. 8 - Setting H2 valve.. 9 - Starting controllers.. 10 - Waiting for temperature.. 11 02 - The stop sequence controller function Available result values : 0 - Resetting system.. 1 - Closing H2 valve.. 2 - Opening system valve.. 3 - Opening system valve.. H-Cube® User Manual v. 2. 7. page:72 of 75 4 - Resetting system.. 5 - Resetting system.. 603 - The shutdown sequence controller function Available result values : 0 - Initializing.. 1 - Setting valves.. 2 - Exhausting H2.. 3 - Exhausting H2.. 404 - The H2 emptying sequence controller function Available result values : 0 - Initializing.. 1 - Closing H2 valve.. 2 - Opening WS valve.. 3 - Opening WS valve.. 4 - Close WS valve.. 5 - Close WS valve.. 6- The parameter readers : GP - Get the system parameter value GP? --> --------------------------------------------------------------------------------------------------------------------------------------------Parameter #1 : The parameter code. Parameter #2 : Results : The parameter value State : No constraint. Available values for the parameter #1 00 - Hydrogen generator cell voltage in 1/10 V, between 0 and 50 01 - Hydrogen sensor state flag, 0 when no hydrogen leak, 1 when hydrogen leak detected 02 - Hydrogen Hydrogen sensor fan signal pin. The value is 0 or 1. 03 - Water flow pin. The value is 0 when flow not detected, and 1 when flo w is detected. 04 - Front door pin. Not used. 05 - Interlock pin. Not used. 06 - Current state Available result values : 0 - Starting 1 - Running 2 - Stopping 3 - Ready 4 - Startup 5 - Shutdown 6 - Checking H-Cube® User Manual v. 2. 7. page:73 of 75 07 - Info message code. Available result values : 155 156 - OK 157 - Switch on the pump. 158 - Switch off the pump. 159 - Building pressure... 160 - Building temperature... 161 - Resetting system... 162 - Stabilizing... 163 - Stable. 168 - Initializing.. 169 - Close H2 valve.. 170 - Starting HPLC pump.. 171 - Waiting for user.. 172 - Change screen.. 173 - Starting controllers.. 174 - Building pressures.. 175 - Setting H2 valve.. 176 - Setting H2 valve.. 177 - Starting controllers.. 178 - Waiting for temperature.. 179 180 - Resetting system.. 181 - Closing H2 valve.. 182 - Opening system valve.. 183 - Opening system valve.. 184 - Resetting system.. 185 - Resetting system.. 186 187 - Initializing.. 188 - Setting valves.. 189 - Setting valves.. 190 191 - Initializing.. 192 - Setting valves.. 193 - Exhausting H2.. 194 - Exhausting H2.. 195 196 - Initializing.. 197 - Closing H2 valve.. 198 - Opening WS valve.. 199 - Opening WS valve.. 200 - Close WS valve.. 201 - Close WS valve.. 202 08 - Active screen Available result values : 0 - Logo 1 - Startup 2 - System 3 - System 4 - Service 5 - Shutdown H-Cube® User Manual v. 2. 7. page:74 of 75 6 - Shutdown dialog 7 - Instrument off message 8 – Water flow error message 9 – Water flow error dialog 10 - Pressure error message 11 - Pressure error dialog 12 – Water level error message 13 – Water level error dialog 14 - Water pump error message 15 - HPLC pump error message 16 - H2 off message 17 - H2 off dialog 09 - Shutdown type. Available result values : 1 - Hydrogen sensor signal occurs. 2 - Hydrogen sensor fan error signal occurs. 4 - Hydrogen pressure limit exceeded exc eeded error occurs. 10 - The hours of the instruments. (0-65535) 11 - The minutes of the instruments. (0-60) 12 - The stable state (0: not stable, 1: stable) 13 - The H2 amount value in NmL/min. (0-25) 14 - The water level codes Available result values : 0 - Empty, stop the process. 1 - Low 2 - Enough 3 - Full 15 - The flag of the purge function. 0 if disabled, 1 if enabled. 16 - The hours of the Hydrogen cell 17 - The minutes of the Hydrogen cell 18 - The error error flag for the Hydrogen cell 19 - H2Cell status message Available values for the result 141 : When no H2Cell error 142 : When H2Cell error 20 - Valves status message Available values for the result 141 : When valves are not in move.. 146: When setting valves, i.e. valves are in move. 142 : When valve valve actual position does not not equal to valve set position within a range of +/ - 4 for more than 30 30 sec ( error ) 21 - Heater status message Available values for the result 147 : When not heating. H-Cube® User Manual v. 2. 7. page:75 of 75 148 : When heating 142 : When the temperature of the t he heater larger than 130C 22 - Water flow status message Available values for the result 141 : When water flow is OK. 142 : When no water flow signal after pumping pulse H-Cube® User Manual v. 2. 7. page:76 of 75

Thales Nano H Cube Hydrogenation Reactor ThalesNano Hydrogen Manual

Recommend Documents