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Gas phase methanol synthesis for carbon-11 radiopharmaceuticals Van Lier, Erik 2007

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GAS PHASE M E T H A N O L SYNTHESIS FOR CARBON-11 RADIOPHARMACEUTICALS  by  E r i k van L i e r  B . E n g . , M c G i l l University, M a y 2001  A THESIS S U B M I T T E D IN PARTIAL F U L F I L L M E N T O F  THE REQUIREMENTS FOR THE DEGREE OF  MASTER OF APPLIED SCIENCE  in  T H E F A C U L T Y OF G R A D U A T E STUDIES  ( C h e m i c a l and B i o l o g i c a l  Engineering)  T H E UNIVERSITY OF BRITISH C O L U M B I A  August 2007  © E r i k van L i e r , 2007  Abstract Carbon-11 radiopharmaceuticals are gaining an increasing importance i n positron emission tomography due to their importance i n diagnostic medicine. T h e most w i d e spread method o f production o f these radiopharmaceuticals is by methylation of an appropriate precursor w i t h the h i g h l y reactive [ C ] m e t h y l iodide. Conventional synthesis o f this intermediate n  involves l i q u i d phase synthesis o f [ C ] m e t h a n o l , w h i c h is the step that limits the specific n  activity of the final product. A catalytic gas phase methanol synthesis process was evaluated, that promises to avoid the loss o f specific activity. In this procedure, [ C ] c a r b o n n  dioxide produced i n the target is first trapped and purified, then converted to [ C ] c a r b o n n  monoxide using m o l y b d e n u m and finally reduced to [ C ] methanol using a copper zinc n  oxide catalyst i n the presence o f hydrogen. In this study a device to trap and purify [ C ] c a r b o n dioxide was developed and optin  m i z e d . [ C ] C a r b o n d i o x i d e produced i n target was quantitatively trapped at -20° C on a n  carbon molecular sieve c o l u m n and quantitatively released i n less than 3.5 minutes. A reactor to convert 50 p p m carbon d i o x i d e to carbon monoxide, based on the reaction w i t h m o l y b d e n u m , was developed. A c o m m e r c i a l l y available process simulator was used to assist the optimization o f operating conditions and m o l y b d e n u m pretreatment methods. U n d e r optimal conditions, carbon d i o x i d e was converted to carbon m o n o x i d e w i t h over 70% yield. A reactor to catalytically convert 50 p p m carbon monoxide to methanol was developed. A copper zinc oxide catalyst was prepared by a co-precipitation method. T h e catalyst was  ii  activated by reduction with hydrogen and passivated w i t h compressed air prior to methanol synthesis. T h e effect of temperature, pressure and flowrate on the conversion o f carbon monoxide to methanol were studied and results were used to create a kinetic model. This model was used to determine optimal operating conditions for this reactor and predicts 6 0 % conversion o f [ C ] c a r b o n monoxide to [ C ] m e t h a n o l . n  n  These findings suggest that gas phase [ C ] methanol synthesis is a viable alternative to n  the conventional l i q u i d phase method, meriting further studies with carbon-11.  iii  Contents  Abstract  «'  Nomenclature  x  Acknowledgements  1  Introduction  1  1.1  Background  1  1.1.1  Positron emission tomography  2  1.1.2  Application of P E T  7  1.1.3  Carbon-11 radiopharmaceuticals  8  1.2  2  xv  Objective o f the study  9  Literature review  11  2.1  Radiochemistry o f carbon-11  11  2.1.1  Production o f C-11  12  2.1.2  Recovery and purification of C 0  2.1.3  Reduction o f C 0  2.1.4  Synthesis o f C H O H  20  2.1.5  Synthesis o f carbon-11 radiopharmaceuticals  22  2.2  n  n  and C H n  2  and oxidation of C H  4  U  2  4  u  3  14 17  M o l y b d e n u m compounds for the reduction of C 0 to C O  23  2.2.1  23  2  History  iv  2.3  2.2.2  Reduction o f m o l y b d e n u m oxides  2.2.3  Oxidation of molybdenum  2.2.4  Interaction o f C 0  2  .  24 26  and C O w i t h M o C  27  2  M e t h a n o l synthesis  30  2.3.1  History  30  2.3.2  Catalyst preparation  31  2.3.3  Catalyst poisoning / deactivation  32  2.3.4  Thermodynamics and kinetics  32  3 Experimental: Trapping and purification o f C 0  34  1 1  2  3.1  Introduction  34  3.2  Materials and methods  35  3.3  Experimental set-up . ;  3.4  Experimental procedure  3.5  '.  36  3.4.1  Production o f  3.4.2  Trapping and release o f  1 1  36  C0  .  2  37 1 1  C0  39  2  Results and discussion  40  3.5.1  Effect o f carbon molecular sieve mass on  3.5.2  Effect o f trap temperature on C 0  3.5.3  O v e r a l l trapping efficiency  1 1  C 0 trapping efficiency 2  trapping efficiency  2  41 42 43  4 Experimental: Reduction of C 0 to CO  44  2  4.1  Introduction  44  4.2  Preliminary experiments: reaction o f C 0 n  2  and M o  44  4.2.1  Materials and methods  44  4.2.2  Experimental set-up  45  4.2.3  Experimental procedure  46  4.2.4  Results and discussion  46  v  4.3  4.4  5  4.3.1  Reduction o f M o 0  4.3.2  Oxidation of M o with 0  3  with H  . .  49  2  50  2  C o l d experiments: reaction o f C 0  48  2  and M o  54  4.4.1  Introduction  54  4.4.2  Materials and methods  55  4.4.3  Experimental set-up  56  4.4.4  Experimental procedure  57  4.4.5  Results and discussion  59  Experimental: Methanol synthesis  65  5.1  Introduction  65  5.2  Materials and methods  66  5.2.1  67  5.3  5.4  6  E q u i l i b r i u m computer simulations o f systems containing m o l y b d e n u m  C u / Z n O catalyst preparation  Experimental procedure  68  5.3.1  Preliminary experiments: C u / Z n O catalyst for C H 3 O H synthesis . .  68  5.3.2  Effect o f flowrate and temperature on C H 3 O H synthesis  69  Results and discussion:  71  5.4.1  P r e l i m i n a r y experiments: C u / Z n O catalyst  71  5.4.2  Effect of flowrate and temperature on C H O H synthesis  73  5.4.3  Kinetic Model  76  3  Conclusion and Recommendations  80  6.1  Conclusions  80  6.2  Recommendations for future w o r k  81  Bibliography  83  vi  Appendices  91  A p p e n d i x I: Flowmeter calibration curves  91  A p p e n d i x II: Calibration curves  93  A p p e n d i x III: Surface molybdenum  96  A p p e n d i x IV: Temperature profile  98  A p p e n d i x V: Process simulator  100  A p p e n d i x VI: Carbon dioxide estimate  105  vii  List of Tables 3.1  C - l 1 target yields, 14 M e V  3.2  n  3.3  n  40  C 0  2  trapping/releasing Sequence  41  C 0  2  trapping efficiencies  41  3.4  C o m p a r i s o n o f overall trapping efficiency  4.1  U  C0  2  43  Reduction sequence  47  4.2  S u m m a r y of C O yields, 17.5-70 c m / m i n , 2 b a r  5.1  Effect o f flowrate on conversion o f C O to methanol (50bar, 1 8 0 ° C )  5.2  Effect of temperature on conversion of C O to methanol at 55bar,  u  47  3  . . . .  74  126  cm /min(STP)  74  5.3  K i n e t i c parameters for L e o n o v ' s model  76  6.1  M o surface moles rough estimate  96  6.2  M o total moles  97  6.3  C0  3  2  concentration estimates  105  viii  List of Figures 1.1  Conceptual visualization o f a cyclotron  3  1.2  Interior v i e w o f the P E T T R - 1 9 cyclotron  4  1.3  A n n i h i l a t i o n o f a positron . .  5  1.4  C o m m e r c i a l P E T scanner  6  1.5  1 8  F D G - P E T scan o f a breast cancer patient  7  2.1  Separation o f air, C O , C H and C 0  2.2  Separation o f H , air, C H and C 0  2.3  Decay corrected  2.4  C O formation rate from temperature programmed reaction o f C 0  3.1  1 1  3.2  1 1  4.1  n  4.2  E q u i l i b r i u m compositions of M o - M o O - M o 0 - M o 0 - H - 0 - H 0 from 300  4  2  4  n  using gas chromatography  2  2  17  using gas chromatography  18  C O yields as a function o f temperature  28 2  with M o C 2  C 0 Trapping experimental flow diagram  37  C0  activity vs. time, for different trap temperatures  42  Reduction experimental flow diagram  45  2  C 0  2  2  2  3  2  2  2  to 1500 K 4.3  29  50  E q u i l i b r i u m mole fraction o f M o 0  2  for different H : M o 0 2  3  to 1 5 0 0 K  ratios from 300 51  4.4  E q u i l i b r i u m o f composition o f M o - M o 0 - M o C - C 0 - C O  52  4.5  E q u i l i b r i u m molar fraction o f C 0  53  4.6  E q u i l i b r i u m molar fraction of C O from eqs. 4.6  2  2  2  from eqs. 4.5  ix  2  53  4.7  Conversion o f C 0 to C O vs. temperature for different C 0 2  2  concentration,  based on A s p e n e q u i l i b r i u m data  54  4.8  Experimental flow-diagram for the reduction o f C 0  4.9  Effect of temperature on reaction o f C 0  4.10 Effect o f flowrate on reaction o f C 0  2  57  2  and M o , at 4 c m / m i n and 2 bar . 3  2  and M o at 8 2 5 ° C and 2 bar  60 61  4.11 Total carbon oxides as a function o f temperature  62  4.12 Total carbon oxides as a function o f flowrate  62  5.1  Experimental flow diagram for methanol synthesis  68  5.2  A s p e n generated e q u i l i b r i u m conversion o f 50 p p m C O to methanol, i n hydrogen  69  5.3  M e t h a n o l produced for continuous feed o f H / C O  72  5.4  Semi-batch methanol produced, 1 8 0 ° C , 50 bar for different  5.5  Semi-batch methanol produced, 120 c m / m i n , 50 bar for different temper-  2  flowrates  . . .  73  3  atures  75  5.6  Conversion o f carbon monoxide to methanol vs. temperature  77  5.7  Conversion o f carbon monoxide to methanol vs.  78  6.1  M a s s flow control valve calibration curve  92  6.2  Correlated ball flowmeter calibration curve  92  6.3  Gas chromatogram o f C O containing sample  94  6.4  C 0 , C O and C H O H calibration curves  95  6.5  Reactor temperature profile, at 7 4 0 ° C  99  6.6  E q u i l i b r i u m relationships at atmospheric pressure M o - C - M o C - H - C H  6.7  A s p e n generated e q u i l i b r i u m relationships at atmospheric pressure M o - C -  2  flowrate  3  2  Mo C-H -CH 2  2  2  4  . . 101  102  4  x  Nomenclature a  Alpha particle: 2 protons and 2 neutrons  <p  Diameter  £ '  Trapping Efficiency, ratio of the amount of C-l 1 trapped to the amount of C - l l  T  entering the trap £  Recovery Efficiency, ratio of the amount of C - l l released from the trap to the  T  amount of C-l 1 released from the target A  Mass number: number of protons + number of neutrons  i.d.  Inner Diameter  I  Length  iV  Activity remaining after initial activity NO has decay for time t  ATj  Initial amount of activity  o.d.  Outer Diameter  P  Particle emitted  Pi  Incident Particle  p  Proton  e  xi  t  Synthesis time, minutes  t  l/2  t  T  H a l f life: 20.4 minutes for  n  C  Trap time: time elapsed betwen begin of target unloading until C - l l is recovered from the trap  TPR  Temperature Programmed R e d u c t i o n  X  Target Nucleus  X'  Residual Nucleus  y  Y i e l d , defined as the amount o f final product ( m C i ) divided by the amount o f starting mateiral ( m C i )  y'  D e c a y corrected y i e l d , defined as the y i e l d assuming no decay o f product occured  Z  A t o m i c number: number o f protons  mCi  M i l l i C u r i e s , unit o f radioactivity define to be the decay rate o f 1.00 g radium, w h i c h corresponds to 37 b i l l i o n disintegrations per secon  C C H 3 0 H Concentration methanol, p p m  CCO  Concentration carbon monoxide, p p m  C C 0 2 Concentration carbon d i o x i d e , p p m  Ea  A c t i v a t i o n energy  EOB  E n d o f Bombardment  F  Flowrate, gas flowrate defined in standard cubic centimeters per minute  FID  F l a m e Ionization Detector  xii  I  Proton beam intensity, in microamperes  IBS  Ion B e a m Stop  id  Inner Diameter  k  Reaction rate constant  Keq  E q u i l i b r i u m constant  ko  Reaction rate pre-exponential factor  L i A l H 4 L i t h i u m a l u m i n u m hydride n  N u m b e r o f experiments repeated at same conditions  od  Outter Diameter  PET  Positron E m i s s i o n Tomography  Pi  Component i partial pressure  R  Ideal gas law constant  r  M e t h a n o l formation reaction rate  S T D E V Standard D e v i a t i o n STP  Standard Temperature and Pressure  T  Temperature  TEC  T h e r m o Electric C o o l e r  THF  Tetrahydrofuran  TPR  Temperature Programmed Reduction  UHP  U l t r a H i g h Purity  xiii  Vi  Input Voltage, defined as the input voltage signal supplied to the mass flow controller, in volts  xiv  Acknowledgments I would like to thank my supervisors at UBC, Dr's. Dusko Posarac, C.J. Lim and E. Kwok, as well as my mentors at Ebco Technologies Inc., Dr's. R. Johnson and K. Erdman, for their guidance and support. I also would like to thank my colleagues at Ebco Technologies and Advanced Cyclotron Systems Inc. and fellow students and machine shop from the Department of Chemical and Biological Engineering for their assistance with technical issues and their continued support. Finally, I would like to acknowledge the Science Council of British Columbia, National Science and Engineering Research Council of Canada and Ebco Technologies for making this project possible. Finally, I would like to thank my family for their support.  xv  Chapter 1 Introduction 1.1  Background  Short half-life radiopharmaceuticals are used in nuclear medicine together with positron emission tomography (PET) cameras to visualize organ function, particularly of the brain and the heart. PET clinics routinely use radiopharmaceuticals as a diagnostic tool for various disease conditions including cancer. Since the early 1970's, the number of radiopharmaceuticals labeled with the positron-emitting radionuclide carbon-11, has rapidly increased. The most widely used carbon-11 labeling method involves methylation of an appropriate precursor, using [ C]methyl iodide as an intermediate [1]. 11  For many medical applications it is essential that the radiopharmaceutical possesses a high specific activity [2], i.e. a high concentration of radioactivity per unit mass. The process for production should permit sequential automated production runs, while minimizing operator exposure to radiation. Producing high specific activity [ C]methyl iodide with n  sufficient yield has been one of the major challenges in developing a process for the routine production of carbon-11 radiopharmaceuticals [3, 4].  1  1.1.1  Positron emission tomography  The in vivo study o f biochemical processes, i.e. molecular i m a g i n g , became a reality i n the second half o f the 20th century [5, 6]. Discoveries made i n nuclear physics i n the 1930's gave rise to the conceptual idea o f measuring biochemistry i n vivo [7, 8]. A l t h o u g h radioisotopes could be produced, there were several technological barriers preventing the transfer o f this technology to a c l i n i c a l setting.  Scintillation crystals were discovered  around 1950 [9] and computers for data acquisition and processing were only available at a later date. The first positron camera was constructed i n the 1960s [10]. Ten years later, groups i n Europe, Japan and N o r t h A m e r i c a produced P E T radiopharmaceuticals and developed P E T scanners [10]. T h e major steps involved i n P E T i m a g i n g are production o f the radioisotope w i t h a particle accelerator, synthesis of the appropriate radiopharmaceutical and in vivo visualization of the b i o l o g i c a l uptake w i t h 3-dimensional P E T scanners.  Particle accelerators T h e first step i n P E T is the production o f the appropriate radionuclide by bombarding a target material w i t h accelerated protons or deuterons. This can be accomplished using a linear accelerator or a cyclotron; most P E T facilities use a cyclotron due to l o w e r overall cost and physical size. In a linear accelerator, particles travel d o w n a long, straight track and collide w i t h the target. In a cyclotron, particles travel i n a circular orbit until they reach the required energy and collide w i t h a target. A conceptual visualization o f a cyclotron is illustrated i n F i g u r e 1.1. It consists o f a pair o f hollow, semicircular metal electrodes (dee's), positioned between the poles o f a large magnet. The dee's are separated from one another by a narrow gap and enclosed i n a high vacuum chamber. A n external source o f ions (typically H ~ ) supplies charged particles to the center o f the cyclotron. A s they enter the cyclotron, the radio-frequency ( R F ) accelerator alternates the  2  PRODUCTION T A R G E T  Courtesy of Ebco Technologies Inc. [ 1 1 ] Figure 1.1: Conceptual visualization of a cyclotron electric field between the dee's within the cyclotron. The incoming ions are exposed to this electric field as well as a strong magnetic field generated by the main magnet, accelerating the negative ions in a circular path. As the number of orbits increases, so does their speed and energy. When the desired energy is reached, the electrons are stripped off the negatively charged ions by a carbon extraction foil, and the resulting positive ion beam is thus extracted from its orbit. The resulting proton (or deuteron) beam collides with the target material to produce the desired radioisotope. Figure 1.2 illustrates a modern cyclotron, with the main vacuum chamber open.  Radioisotope production  A general form to describe a nuclear reaction between the target material and the accelerated proton or deuteron is shown in eq. 1.1 [ 1 2 ] , where X is the target material, P; is the incident particle, X ' the generated radioisotope, and P the emitted particle. e  3  RF Dees  Courtesy o f E b c o Technologies Inc. [11] Figure 1.2: Interior view o f the P E T T R - 1 9 cyclotron  £x+p  ;  -> t:x' + p  } N +  p  ->  4  (i.i)  e  I'C + a  (1.2)  T h e production o f carbon-11 (eq. 1.2) involves the bombardment o f nitrogen gas with an incident beam o f protons, w h i c h creates a very unstable oxygen-15 intermediate [13] containing 8 protons and 7 neutrons. T h i s intermediate instantaneously stabilizes by emitting an alpha particle (2 protons, 2 neutrons), to y i e l d the radionuclide carbon-11, w h i c h has 6 protons and 5 neutrons. C o m m o n radionuclides produced w i t h a medical cyclotron are 1 3  N (ti/2 = 10 min),  15  0 (t  1 / 2  = 2 min) and  1 8  F (t  1 / 2  = 110 min).  n  C (ti/  2  = 20.4 min),  These radionuclides  decay by pure positron emission, as illustrated by the decay o f carbon-11 i n eq. 1.3. T h e half life is a characteristic constant for a given radioisotopes and corresponds to the time 4  required for half of a radioactive sample to decay [14].  n ^l°B  +P  (1.3)  +  C  In addition to their short half lives, the principal positron emitters C , N , n  1 8  1 3  1 5  0 and  F are useful for clinical P E T since their stable isotopes are the building blocks for most  organic molecules ( F is used in place of H or OH). The radionuclides are chemically 18  processed to prepare a radiopharmaceutical that will target the desired metabolic process or tissue in the body.  P E T Cameras  Positrons ((3 ) travel at most a few millimeters before they are annihilated with nearby +  electrons to give two gamma rays of 511 keV emitted in opposite directions (Figure 1.3).  0.51 MeV  Gamma photon  Before •  +  electron  positron  Best mass of each  0.51 MeV  is 0 51 MeV  Gamma photon  Figure 1.3: Annihilation of a positron The P E T camera uses rings of detectors that register the 511 keV rays from a single annihilation. The detectors are arranged in a circle around the patient, or in a hexagonal array where the detectors are grouped into cassettes. The content of each cassette varies 5  according to the manufacturer, but usually these consist o f 256 scintillating crystals being viewed by 16 photomultiplier tubes (four blocks composed o f 64 crystals and four photomultiplier tubes) w i t h as many as three rings of 16 buckets i n a circle (12,288 crystals w i t h 768 photomultiplier tubes) [15]. A n alternative design to the bucket, is one that uses rings of detectors w i t h 11 crystals in a staggered array being exposed to 6 photomultiplier tubes [15]. A s can be seen i n Figure 1.4, once the patient is placed inside the scanner, he/she slowly moves through the rings o f detectors to provide a whole or partial body scan.  Figure 1.4: C o m m e r c i a l P E T scanner  W h e n two detectors at opposite sides o f the camera simultaneously detect a gamma ray, the data processor assumes that on the virtual line connecting the two detectors a positron was annihilated. Once sufficient data is collected, a 3-dimensional image o f the radiation distribution can be generated. F o r example, Figure 1.5 shows the  1 8  F D G uptake in a patient  w i t h breast cancer, revealing that numerous active metastatic cancer sites are present.  6  Courtesy D r . F. Benard Figure 1.5:  1.1.2  1 8  F D G - P E T scan o f a breast cancer patient  Application of PET  P E T is currently used c l i n i c a l l y i n cardiology, neurology, and oncology. T h e most c o m m o n radiopharmaceutical used i n P E T is [ F]fluoro-deoxy-glucose ( F D G ) [16], w h i c h allows 18  the measurement o f glucose consumption i n vivo and detects organs and tissues w i t h h i g h metabolic activity. A p p l i c a t i o n s o f P E T in cardiology also include measurement o f b l o o d flow w i t h  1 3  NH  and/or [ C ] a c e t a t e , i n addition to the studies on the glucose consumptions n  3  of the heart w i t h with  1 8  1 8  F D G [17]. A p p l i c a t i o n s in neuroscience include glucose metabolism  F D G , protein synthesis rate with [ C ] t y r o s i n e and b l o o d flow w i t h H  oncology,  n  1 8  l s 2  O [18]. In  F D G - P E T is a major tool for diagnostic and treatment follow-up. In addition  to F D G , [ ^ m e t h i o n i n e , J  [ C ] t h y m i n e , [ ^ c y t o s t a t i c s are used for imaging o f more n  J  specific cancers. Positron emitter labeling w i t h carbon-11, nitrogen-13 and oxygen-15, can be used to investigate the catalytic processes and to quantify reaction phenomenon, y i e l d i n g insight i n  7  elementary reaction mechanisms useful as input to mathematical simulations [19].  1.1.3  Carbon-11 radiopharmaceuticals  Carbon-11 radiopharmaceuticals are finding an increasing number o f applications i n cardiology, neurology, and oncology [18]. M a n y applications, such as brain i m a g i n g , require high specific activity radiopharmaceuticals. F o r example, [ C ] r a c l o p r i d e , w h i c h is used n  to visualize dopamine receptors i n the brain, requires a high specific activity since only a small number o f dopamine receptors are available. L o w specific activity, i.e. the presence of many [ C ] r a c l o p r i d e molecules, may result i n receptor saturation and poor image qual12  ity. M a n y [ C ] r a d i o p h a r m a c e u t i c a l s are synthesized by the methylation o f an appropriate n  precursor w i t h [ ^ m e t h y l iodide, w h i c h i n turn is generally prepared from [ C ] m e t h a n o l . x  U  Production of carbon-11 radiopharmaceuticals Carbon-11 is produced i n a cyclotron by the bombardment o f a gas target filled w i t h n i trogen, using a proton beam (typically 10-19 MeV), v i a the  1 4  N ( p , a ) C nuclear reaction. n  In the presence o f 0 , the carbon-11 is produced as C 0 , w h i l e i n the presence o f H , n  2  n  CH  4  2  2  is produced. A sequence o f chemical reactions is carried out to convert these pre-  cursors to a carbon-11 radiopharmaceutical, typically v i a the [ C ] C H O H and [ C ] C H I n  n  3  3  intermediates. T h e conventional synthesis o f [ C ] m e t h y l iodide most w i d e l y used over the past 30 n  years [20] involves two m a i n reactions: the reduction o f C 0 n  to C H O H , followed by n  2  3  iodination to y i e l d C H I (eq. 1.4) [20]. n  3  LiAlH  HI  A  C0  ->  n  2  In the l i q u i d phase synthesis, C 0  CH OH  n  3  n  2  _> CH I n  3  (1.4)  is bubbled through a solution of l i t h i u m a l u m i n u m  8  hydride ( L i A l H ) for the production of C H O H , which is then treated with HI to yield u  4  n  3  C H I . The L i A l H is a strong reducing agent and is readily contaminated with C 0 from 3  4  2  the atmosphere during preparation of the reagent. Consequently, relatively low specific activity [ C]methyl iodide is generally produced. The quantity of L i A l H utilized in the n  4  reaction has a great influence on the yield and specific activity of C H O H [13]. Large n  3  quantities of L i A l H in the reactor give rise to high yields with low specific activity. On the 4  other hand, small amounts of L i A l H lead to low yields but with higher specific activity. 4  Thus, the main drawback of this method is that a sufficient yield cannot be obtained while simultaneously achieving a high specific activity. Alternative methods, include the gas phase production of [ C ] methyl iodide by reactn  ing C H U  4  with I [21, 22]. This synthesis route avoids the use of L i A l H and consists of 2  recirculating C H  4  n  1.2  4  with iodine vapor through a hot reactor.  Objective of the study  The conventional method to produce many carbon-11 radiopharmaceuticals involves the L i A l H reduction of C 0 U  4  2  and is not suitable for production of high specific activity ra-  diopharmaceuticals. The main objective of this study was to determine the feasibility of an alternative gas phase process involving catalytic methanol synthesis, which providing a process for the production of large quantities of high specific activity carbon-11 radiopharmaceuticals. The proposed gas phase reaction route consists of the reduction of C 0 to C O followed 2  by catalytic reduction of C O to C H O H . 3  The steps leading to methanol synthesis will be developed and optimized. Detailed objectives of the present study include: 1. To design / implement / optimize performance of C 0 trapping device 2  2. To design / implement / optimize performance of reduction of C 0 t o C O 2  9  3. To design / implement / optimize performance of reduction of CO to C H O H 3  4. To develop an empirical rate equation for methanol synthesis to predict performance using carbon-11  10  Chapter 2 Literature review T h i s chapter is divided i n three sections. T h e first section deals w i t h the radiochemistry of carbon-11. T h e second section provides i n depth information o f the reactions o f carbon oxides and m o l y b d e n u m compounds. T h e third section includes history and background information on industrial methanol synthesis.  2.1  Radiochemistry of carbon-11  Since the early 1970's, when medical cyclotrons where introduced, an increasing number of compounds are labeled w i t h the positron emitting radionuclide carbon-11 [23].  The  most w i d e l y used method to produce carbon-11 radiopharmaceuticals involves the methylation o f an appropriate precursor w i t h [ C ] m e t h y l iodide [2]. B a s e d on this method, a n  large number o f receptor-ligands have been investigated [24]. These radiopharmaceuticals require a high specific activity and it is thus important that each step i n their production m i n i m i z e s contamination w i t h carrier carbon-12. T h e conventional method for the preparation o f I  1  methyl iodide is the reduction o f  [ C ] c a r b o n dioxide to [ C ] m e t h a n o l by lithium a l u m i n u m hydride, f o l l o w e d by conver11  n  sion to [ C ] m e t h y l iodide w i t h hydroiodic acid [25]. A n alternative method used by many n  P E T centers involves a recently developed gas phase method, w h i c h consists o f reacting 11  [ C]methane with iodine vapor to give [ C]methyl iodide [21, 22, 26]. n  u  Throughout this work the terms yield and decay corrected yield are frequently used. The yield is defined as the ratio of the amount of radioactive product to the amount of radioactive starting material, as shown in eq. 2.1. Although synthesis time does not show up directly in this equation, it is incorporated in the yield since a certain amount of C-11 is lost due to decay during the synthesis. However, in order to quantify the efficiency of the various steps in the process, it is desirable to calculate the decay corrected yield, also referred to as the radiochemical yield. It is calculated by multiplying the yield by a decay correction factor, which depends on the time elapsed and the half life of the radionuclide in question, as shown in eq.2.2. The decay corrected yield refers to the yield assuming no radioactive decay occurred, and is also referred to as the chemical yield. Amount Product (mCi) Amount of Reagent (mCi)  ^ y'  =  yexp 0  6  9  3  ^  ''/'^  (2.2)  For example, consider a process which has a 30% yield ( C 0 U  to C H O H ) with 11  2  3  synthesis time of 20.4 minutes. Since the half life of carbon-11 is 20.4 minutes, the decay corrected yield is 60%. Thus the actual chemical conversion of [ C]carbon dioxide to n  [ C]methanol is 60%, but since half of the carbon-11 decayed, the actual yield is only n  30%.  2.1.1  Production of C - l l  Although several nuclear reactions can be used to produce carbon-11, the most convenient is the N ( p , a ) C reaction using natural occurring nitrogen gas. Carbon-11 can be pro14  n  duced in the gas target as C 0 n  the nitrogen, while for C H n  4  or C H ; in the case of C 0 n  2  n  4  2  0.1-2% oxygen is added to  production 5-10% hydrogen is added to the nitrogen gas.  The natural abundance of C 0 in the air is 330 ppm, whereas that of methane is 1.6 ppm. 2  12  T h i s means that m u c h precaution must be taken to exclude air from synthesis modules and reagents during synthesis with  n  C0 . 2  However, specific activities o f C 0  and  n  2  n  CH  4  produced i n target are reported to be similar. F o r i n target production o f C H , a specific n  4  activity of 5 Ci/u-mol was reported [27, 28]. F o r i n target production o f C 0 , specific n  2  activities up to 16.5 Ci/iamol were reported [29]. A n independent study demonstrated that only a negligible amount o f carrier  1 2  C0  originates from the target [24]. [ C ] M e t h a n e n  2  production yields are typically less than 6 5 % o f [ C ] c a r b o n d i o x i d e yields [28]. These n  factors are among the reasons that many P E T centers routinely produce to  n  1 1  C 0 as opposed 2  CH . 4  Target for C - l l production Pure a l u m i n u m , a l u m i n u m alloys and stainless steel are suitable materials for target construction. H a v a r ® , titanium or stainless steel are suitable materials for the target w i n d o w foils. M e t a l gaskets are preferable to rubber O-rings [13]. In order to reduce potential carrier carbon and increase specific activity, ultra-pure materials w i t h very l o w carbon content should be used. Thus, ultra pure a l u m i n u m w o u l d be suitable as target body and ultra pure titanium foil for the target w i n d o w . F o r good recovery of C - l 1 from the target, it is recommended that newly constructed targets be carefully washed with phosphoric acid followed by water, and dried under vacuum. The target gas should be o f high purity and i n particular as free as possible from carboncontaining impurities. A n additional precaution against [ C ] c a r b o n d i o x i d e contamination L2  w o u l d be to introduce a carbon dioxide trap i n between the nitrogen gas cylinder and the target and also to use stainless steel tubing to m i n i m i z e entry of carrier  1 2  C0  2  by diffusion  [13].  n  y  U  C  °  2  "  CQ  2  Produced(EOB)  I- ( 1 - e x p ( - 0 . 6 9 3 - t / t ) ) 1/2  13  (  2  3  )  An important characteristic for a target is the C 0 yield at the end of bombardment n  2  (EOB). As can be seen in eq. 2.3, the C 0 yield depends on the amount of C 0 pron  n  2  2  duced in the target, the half life of C-l 1, the beam intensity (I) and the duration of irradiation (t). For an energy beam of 14 MeV, C-ll experimental target yields vary between 93 and 135 u-Ci/uA [30, 31, 32]. The theoretical target yield, calculated from N(p,n) C 14  n  excitation function, was determined to be 169 (a.Ci/(J.A at 14 MeV [31]. As can be seen from this data, the reported experimental yields are at least 25% less than the theoretical yield.  Recovery and purification of C 0 2 and C H  2.1.2  n  N  4  The target gas is either a mixture of N / H or of N / 0 . The short half life of C-11 makes it 2  2  2  2  necessary to concentrate it rapidly from a large volume of target gas in order to prepare the C-ll radiopharmaceutical [33]. In addition, the carbon-11 produced in the target as C 0 n  2  or C H must be separated from the target gas, in order to remove the 0 or the H , which n  4  2  2  can affect downstream processing of the C-ll radiopharmaceutical [34]. Two common methods exist for recovery of C-l 1, which are the use of a cryogenic trap and/or the use of an adsorbent trap (such as molecular sieve) [13]. The performance or overall trapping efficiency (£T) depends on the amount of C-l 1 released from the target, the amount of C-l 1 released from the trap and the time required for this process. The trapping efficiency (£T0 is defined as the ratio of the amount of C-l 1 trapped to the amount of C-l 1 entering the trap, as shown in eq. 2.4 and indicates how well the trap retains the C 0 . The overall n  2  trapping efficiency is defined as the ratio of the amount of C-ll recovered from the trap to the amount of C-l 1 released from the target, as shown in eq. 2.5. The overall trapping efficiency can also be related to the trapping efficiency and the time required for trapping  14  and releasing the C - l 1, as shown i n eq. 2.6.  t  f  '  C - l l trapped ( m C i )  =  C - l l entering trap ( m C i )  T  C - l l released from trap ( m C i ) C - l l released from target ( m C i ) £  =  T  exp-°-  693  '  tT/tl  (2.6)  /2  Cryogenic C 0 trap: n  2  The trap typically consist o f a small stainless steel tube, (40 cm x d> 0.02 mm). T h e tube is initially immersed i n l i q u i d nitrogen or l i q u i d argon. T h e target gas is then flushed through the c o l d trap w i t h an inert carrier gas such a h e l i u m , thus trapping the [ C ] c a r b o n d i o x i d e . u  T h e [ C ] c a r b o n d i o x i d e is recovered s i m p l y by passing a slow stream o f inert carrier gas n  w h i l e heating the trap to r o o m temperature. T h i s requires r e m o v i n g the trap from the l i q u i d nitrogen bath. C r y o g e n i c C 0 n  2  traps typically have a trapping efficiency of 9 0 % using  a stainless steel tube immersed i n l i q u i d nitrogen or argon w i t h overall trapping/releasing time o f approximately 5 minutes [13]. T h i s corresponds to an overall trapping efficiency of 76%. T h i s method has been further i m p r o v e d , by the use o f a stainless steel frit trap instead o f a tube. |  The trap consist of a 2.25 c m l o n g stainless steel check valve cartridge (for  tubing) w h i c h is packed w i t h eight 20 u r n stainless steel frits. T h e trapping efficiency  was improved to 9 6 % and overall trapping/releasing time was reduced to 3.9 minutes [35]. T h i s corresponds to an overall trapping efficiency o f 84%.  Molecular sieve C 0 trap: U  2  T h e basic principle behind the molecular sieve trap is chromatography. Chromatography is a method of separation that relies on differences i n partitioning behavior between a  15  flowing  mobile phase and a stationary phase to separate the components in a mixture. Molecular sieves have been used as packing for chromatographic recovery of CG*2 [13]. The trap n  typically consists of a column packed with zeolites molecular sieves. The target gas is unloaded through the trap, then flushed with inert gas, and heated to above 200°C for thermal desorption of the C 0 2 . For a column of the following dimensions, I = 6cm, i.d. = 9mm, n  packed with activated 60-80 mesh molecular sieve 4A, the trapping efficiency is above 98% [13]. With an overall trapping/releasing time of approximately 5 min, the trap releases 90% of the carbon dioxide when heated to 230°C. This corresponds to an overall trapping efficiency of 74%. The tenacious affinities of zeolites for both CO2 and water require careful activation before use and rather high thermal desorption temperatures. These inherent characteristics of zeolites lead to the development of an improved molecular sieve trap, with the use of carbon molecular sieves. In contrast to zeolites based materials, carbon sieves are quite hydrophobic in nature and have little affinity for water and small polar molecules. However, they avidly and selectively retain CO2 then release it freely upon the application of modest heat. This is clearly illustrated when comparing the chromatograms of a carbon molecular sieve column at room temperature and at 140°C, as shown in Figure 2.1. A similar trapping procedure has been used, with a 65 cm long trap, 2 mm i.d., packed with 1 g of 80-100 mesh carbon molecular sieve. Trapping efficiency was essentially 100%, and 98% of the n  C0  2  was released from the trap heated to 100°C, with an overall trap/release time of 5  minutes [34]. This corresponds to an overall trapping efficiency of 83%. Control experiments showed that most of the carbon sieves tested did not significantly contribute carrier to the final product [34].  16  C0  12  2  0  2  15 Min.  4  A ) 1. 0 , 2. N , 3. C O , 4. C H 2  2  0  2  4 Min.  B ) 1. A i r , 2. C O , 3. C H , 4. C 0  4  4  2 0 ° C , 45 cm /min H e  140°C, 45 cm /min N  3  2  3  2  Chromatogram, using carbon molecular sieve c o l u m n , obtained from A l l t e c h Inc. [36] Figure 2.1: Separation o f air, C O , C H and C 0 using gas chromatography 4  2  Cryogenic/chromatographic C H trap n  4  In order to increase the retention time o f C H n  4  i n a chromatographic c o l u m n and obtain  separation from target gas, a combination o f cryogenic trapping and chromatography are used.  T h e trap consists o f a tube packed with Poropak N (80-100 mesh).  T h e trap is  initially submerged i n l i q u i d nitrogen, after w h i c h the target is unloaded under controlled flow. A s can be seen i n Figure 2.2, heating to r o o m temperature is sufficient to release the [ C ] m e t h a n e . Trapping methane on Poropak N at - 1 9 6 ° C is less efficient than trapping carn  bon d i o x i d e on molecular sieves [22], w i t h overall trapping releasing time approximately 6.0 minutes. A s s u m i n g that the trapping efficiency is 9 0 % , this w o u l d correspond to an overall trapping efficiency of 7 3 % .  2.1.3 Reduction of C 0 and oxidation of C H n  n  2  Reduction of C 0 U  4  to C O n  2  [ C ] C a r b o n monoxide was one o f the first tracers used for blood flow measurement i n hun  mans [37]. Since it is less reactive than other [ C ] l a b e l i n g agents, it has found little applin  17  T = 35°C, 30 c m / m i n He, 1. H , 2. Air, 3. C H , 4. C 0 Chromatogram, using poropak Q column, obtained from Alltech Inc. [36] 3  2  4  2  Figure 2.2: Separation of H , air, C H and C 0 using gas chromatography 2  4  2  cation as an intermediate in radiopharmaceutical syntheses. However, recently palladium catalyzed cross-coupling reactions for the direct preparation of ketones have been reported [38, 39]. [ C]Carbon monoxide can be produced in situ or by reduction of [ C]carbon n  11  dioxide on the surface of various transition metal elements. A n established method for [ C]carbon monoxide preparation is the reaction of [ C]carbon n  n  dioxide with zinc metal, as illustrated in eq. 2.7. Highest yields are obtained at 400°C which 4  is very near the melting point of zinc (420°C), thus rigorous temperature control is required to avoid melting the zinc. The zinc granules must be thoroughly cleaned before use and require frequent replenishment. Yields are under 50% since a significant amount of radioactivity remains in the reactor [37]. A more recent method for [ C]carbon monoxide preparation is the reaction of [ C]carbon 11  11  dioxide with molybdenum metal (eq. 2.8). The reactor consisted of a 25 m m inner diameter quartz tube and 150 m m long, packed with 2000 m of 0.05 m m diameter molybdenum wire  (99.97% Mo). A helium stream of 25 c m / m i n (STP) was used to transfer the [ C]carbon 3  n  dioxide through the molybdenum reactor, which was kept at a preset temperature. Decay corrected yields of up to 81% were reported with reactor temperature of 800° C [40], with  18  a gas transfer and reaction time of approximately 3 minutes, resulting in a yield of 73%.  n  C 0  + Zn  2  -  ( s )  n  C O + ZnO  (2.7)  ( s )  400°C  2  1 1  C0  2  + Mo  _>  ( s )  2 CO + Mo0  (2.8)  n  2 ( s )  800° C  Reduction of C 0  to C H n  n  2  The reduction of C 0  4  to C H  U  n  2  4  has been carried out for several applications, includ-  ing preparation of [ C]methyl iodide, [ C]methyl triflate and [ C]cyanide [2]. Although n  n  n  [ C]methane can be produced in target, many PET centers choose tofirstproduce [ C]carbon u  n  dioxide and then react it with hydrogen using a nickel catalyst to produce [ C ] methane, as n  illustrated in eq. 2.9.  Ni n  C 0  2  + 4H  2  _,  n  C H  4  + 2H 0 2  (2.9)  450° C  In gas chromatography, flame ionization detectors (FID) are not very sensitive to trace amounts of carbon oxides, but are much more sensitive to methane. Accordingly, nickel based catalyst are frequently used to convert trace amounts of carbon oxides to methane in order to improve the FID sensitivity. In a unique setup, [ C]carbon dioxide is reduced to [ C]methane for production of u  n  [ C]methyl triflate. The reactor consists of a nickel/alumina/silica (64% Ni) powder mixed n  with glass wool packed into a 4 mm inner diameter borosilicate glass tube. The purified  19  [ C]carbon dioxide is swept from the trap with 10% hydrogen in nitrogen. The reactor n  oven is held at 450°C and the gas flowrate is approximately 50 cm /min (STP). Yields 3  of [ C]carbon dioxide to [ C]methane routinely exceed 95% [41] in approximately 2 n  n  minutes, corresponding to a decay corrected yield of over 99%.  2.1.4  Synthesis of C H O H n  3  The established method to prepare [ C]methanol involves the reduction of C 0 n  U  to C H O H n  2  3  using LiAlH ( ). This method produces low specific activity C H O H due to contaminan  4  aq  3  tion of L i A l H with C 0 . To improve the specific activities of C H O H , alternate liquid 1 2  4  n  2  3  phase and gas phase methanol synthesis routes have been investigated.  Liquid phase C H O H synthesis n  3  The conventional process for the reduction of [ C]carbon dioxide to [ C]methanol uses n  u  a solution of L i A l H in tetrahydrofuran (THF), as shown in eq. 2.10. The C 0  recov-  n  4  2  ery from the trap is done with a gas stream of helium or nitrogen at flow rate of 10-100 cm /min (STP). The gas is dried over a dehydrating agent (MgC10 • H 0 or P 0 ) and 3  4  2  2  5  then the gas is bubbled through a solution of L i A l H in T H F The solvent is then evaporated 4  under a stream of nitrogen at approximately 100°C, leaving behind a dry radioactive complex from which [ C]methanol is generated by the addition of water. The [ C]methanol n  n  can be distilled for downstream use or alternatively hydroiodic acid can be added for invial preparation of [ C]methyl iodide. An increase in the amount of L i A l H leads to an n  4  increase in the yield, but a decrease in the specific activity. While a decrease in the amount of L i A l H leads to an increase in the specific activity but a decrease in the yield. The prepa4  ration of methanol typically takes 3-4 minutes with decay corrected yield in the order of 75%, and corresponding yield of approximately 66% [1]. Reported specific activities for [ C]methyl iodide produced via this procedure range from 0.1-1.7 Ci/u.mol [1, 13]. n  In attempts to reduce the amount of L i A l H , a variation of the conventional method has 4  20  been developed, using L i A l H  adsorbed on alumina. T h e alumina cartridge is pretreated at  4  2 0 0 ° C under helium flow, for 1 hour, to desorb water and possible traces of carbon dioxide and then cooled to r o o m temperature. It is then impregnated w i t h 50 u l o f 1 M L i A l H  4  diluted w i t h 200 u.1 diethyl ether. T h e [ C ] c a r b o n dioxide is trapped on the cartridge, u  after w h i c h it is heated up to 1 6 0 ° C under a 50 c m / m i n flow o f helium to remove the 3  solvent. T h e dry complex is then hydrolyzed by injecting 0.01 M phosphoric acid to form [ C]methanol. D e c a y corrected yields o f 9 5 % are reported w i t h [ C ] m e t h a n o l preparation 11  n  time o f approximately 5 minutes, w h i c h corresponds to a y i e l d o f 80%. T h e specific activity o f the downstream produced [ C ] m e t h y l iodide has been reported to be 2-2.5 C i / u - m o l [42, n  13].  l)LiAlH THF 4 l  n  C 0  _>  2  (2.10)  CH OH  n  3  2)H 0 2  H0 2  n  C0 (g)  CH 0~( )  2  3  —>  a q  (2.11)  CH OH 3  Gas phase CH OH synthesis n  3  O n l y a few publications report the catalytic conversion o f [ C ] c a r b o n dioxide to [ C ] m e t h a n o l u  n  according to eq. 2.12.  Cu/ZnO/Al 0 2  n  C 0  2  + 3H  2  _> 150-250°C  21  3  n  CH OH + H 0 3  2  (2.12)  J.T. Patt studied the synthesis of [ C ] m e t h a n o l from [ C ] c a r b o n oxides using Pd/Al C>3 n  n  2  and C u / Z n 0 7 A l 0 2  n  catalysts [43]. U s i n g either catalyst, and a mixture of  3  u  C O and/or  C 0 , A r , H as feed gas, produced negligible amounts o f methanol at 2 0 0 - 2 4 0 ° C and at 2  2  2-3 bar.  The highest methanol yield obtained was 7%, with synthesis time o f 25 m i n , at  240°C and at 2 bar, by adding N 0 to the feed stream [43]. 2  A patent describes a pre-conditioning method o f a catalyst prior to use for [ C ] m e t h a n o l n  synthesis [44]. A copper-zinc oxide catalyst, supported on alumina and/or silica, is first reduced and then preconditioned w i t h a stream o f C O : C 0 : H 2  (1:1:8). Prior to [ C ] m e t h a n o l 11  2  synthesis, the catalyst is heated to 200°C and then gas containing [ C ] c a r b o n d i o x i d e and n  hydrogen is passed through the reactor at a pressure o f 50 bar. T h e [ C ] m e t h a n o l may n  remain adsorbed on the catalyst, and can be removed by addition of a catalyst poison, such as hydrogen sulphide or by increasing the temperature o f the reactor to 280-320°C. T h e y i e l d o f [ C ] m e t h a n o l is 5 7 % and the specific activity ranging from 4-20 C i / u m o l [44]. n  A n alternative method uses CH4 as starting material instead o f 11  of  n  C H , C l and H 4  the  n  CH  2  2  is passed over C r 0 2  3  1 1  C 0 . A mixture 2  on pumice stone at 700°C i n order to oxidize  to C H O H w i t h yields up to 4 5 % [45]. Synthesis time is 2 minutes decay n  4  3  corrected yield of 4 8 % . T h e specific activity o f the subsequently prepared C H I was 1 n  3  C i / u - m o l [45].  2.1.5 Synthesis of carbon-11 radiopharmaceuticals M o s t procedures to synthesize carbon-11 radiopharmaceuticals involve the methylation o f an appropriate precursor. T h e reactivity o f C H O H is insufficient for most applications n  3  and accordingly the C H 3 0 H needs to be converted to a more reactive intermediate, such n  as C H I . T h e preparation o f [ C ] m e t h y l iodide is done by reacting [ C ] m e t h a n o l w i t h a n  n  n  3  source o f iodine, a step that does not affect the specific activity of the product. Traditionally, [ C ] m e t h y l iodide has been prepared by reaction of [ C ] m e t h a n o l with n  n  hydrogen iodide under reflux [13]. The yield is above 9 0 % [45, 42]. A more recent vari-  22  ation o f this reaction route involves the use o f aqueous H I impregnated on alumina, for w h i c h the yield was above 9 7 % at optimal conditions [42]. Alternative iodination agents, diphosphorous tetra-iodide and triphenylphosphine diiodide, have been investigated for the production o f [ C ] m e t h y l iodide[46, 47]. The yields are similar as for the H I procedure, n  however by avoiding the use of volatile H I , the solid reagents allow a cleaner operation. A n alternative procedure, based on the iodination o f [ C ] methane w i t h iodine, has n  been pioneered by Larsen et al. [22, 21]. The reaction is carried out i n a reactor i n w h i c h [ C ] m e t h a n e , helium and iodine vapors are m i x e d and heated. The formed [ C ] m e t h y l n  n  iodide is continuously removed from the reactor w h i l e the unreacted [ C ] m e t h a n e is ren  circulated through the reactor. The synthesis time is 10.5 minutes and reported yields are 5 8 % w i t h specific activity o f 15 C i / i x m o l .  2.2  Molybdenum compounds for the reduction of CO2 to CO  M o l y b d e n u m c o m m o n l y occurs i n nature as the mineral molybdenite, M 0 S 2 , i n quartz rock. F o r this study molybdenum w i l l be used to reduce carbon dioxide to carbon monoxide, by o x i d i z i n g the molybdenum. In this section, the history and chemistry o f m o l y b d e n u m , m o l y b d e n u m oxides and m o l y b d e n u m carbides are presented.  2.2.1 History M o l y b d e n u m was discovered i n 1778, but for the next hundred years, molybdenite was merely a laboratory curiosity. The first major use came during W o r l d W a r I when it was discovered that addition o f molybdenum produced steels with excellent toughness and strength at high temperatures, suitable for use as tank armor and i n aircraft engines [48]. M o l y b d e n u m is mainly used as an alloying element in steel, cast iron, and superalloys to increase hardenability, strength, toughness, and corrosion resistance. However, 23  it has found many other applications i n lighting, electronics, vacuum coating and nuclear medicine. It is also extensively used as a catalyst or as a component thereof [48].  2.2.2  Reduction of molybdenum oxides  Reduction of molybdenum oxides with hydrogen M o l y b d e n u m metal powder is produced industrially by reducing high-purity m o l y b d e n u m compounds, such as m o l y b d e n u m trioxide, a m m o n i u m hexamolybdate or a m m o n i u m d i molybdate, w i t h hydrogen [48]. M o l y b d e n u m metal powder can be produced industrially by reducing M0O3 powder w i t h hydrogen between 5 0 0 - 1 1 5 0 ° C [49]. M o l y b d e n u m trioxide, a gray-green powder is reduced by hydrogen at 500-600°C to M0O2, w h i c h is further reduced at 900-1050°C to m o l y b d e n u m metal. Since the first reduction to M o 0  2  is  exothermic, this step is performed at 600°C to prevent caking due to the melting o f M0O3 ( 8 0 0 ° C). The red-brown M o 0  2  [50] is reduced to metallic molybdenum powder at 1050°C.  The powder has a particle size o f 2-10 u.m, a specific surface area o f 0.1-1 m / g , and an 2  oxygen content o f 100-500 mg/kg (partly adsorbed and partly as oxide) [48]. Thermal decomposition and reduction o f molybdenum trioxide under different reducing conditions has been extensively studied [51, 52, 53]. M o l y b d e n u m trioxide powder was reduced i n pure hydrogen w i t h gradual temperature increase from 300 to 800°C  at  approximately 6 °C/min and isothermally at 600°C. Under these conditions, the reduction o f m o l y b d e n u m trioxide to m o l y b d e n u m dioxide took place at 387-615°C  w h i l e the  reduction to molybdenum metal took place slowly at 6 2 3 - 7 4 0 ° C [ 5 1 ] . L e e et al.  [54] performed temperature programed reduction ( T P R ) o f h i g h purity  molybdenum trioxide, from 300 to 750 °C, i n pure hydrogen, with a heating rate o f 1 ° C / m i n . The gas products obtained during T P R were monitored by gas chromatography, equipped with thermal conductivity detector for the detection o f water. Reduction o f M0O3 to M o 0  2  occurred between 430-620°C, w h i l e complete reduction to m o l y b d e n u m occurred  above 700°C. 24  Iwasawa et al.  [55] found that m o l y b d e n u m dioxide on alumina was reduced w i t h  hydrogen to m o l y b d e n u m at 6 0 0 ° C . In contrast to the one-step reduction mechanism o f m o l y b d e n u m trioxide to m o l y b d e n u m dioxide, B u r c h [56] suggested that M04O11 is an i n termediate product o f the reaction. However, Ressler et al. [53] found that M o O n was also 4  formed by reaction o f different m o l y b d e n u m oxides. Temperature programmed reduction of M 0 O 3 w i t h 5-100% H was studied for temperatures ranging from 3 0 0 - 8 0 0 ° C . B e t w e e n 2  350 and 4 2 5 ° C , the reduction o f M 0 O 3 to M o 0  2  is a one-step process without formation o f  crystalline intermediates. A t temperatures above 4 5 0 ° C , M o O n can be obtained and its 4  formation was explained as the product o f a parallel reaction between m o l y b d e n u m d i o x ide and m o l y b d e n u m trioxide. There is a general agreement between various researchers that at reduction temperatures above 5 0 0 ° C and hydrogen concentrations o f at least 10%, metallic m o l y b d e n u m is produced as the final product according to a two step reduction, as illustrated in eqs. 4.2 and 4.3 [53].  Reduction of molybdenum oxides with carbon monoxide Reduction o f m o l y b d e n u m trioxide w i t h carbon monoxide at 4 0 0 ° C gave carbon dioxide, the reddish-brown m o l y b d e n u m d i o x i d e and unreacted m o l y b d e n u m trioxide [57]. reduction was presumed to proceed according to the eq.  2.13.  The  A t higher temperature  ( 5 6 5 ° C ) , m o l y b d e n u m trioxide i n a stream o f carbon monoxide gave carbon d i o x i d e and a dark-gray almost black material, w h i c h was assumed to be m o l y b d e n u m carbide and free carbon. The overall reaction is illustrated i n eq. 2.15, w h i c h proceeds through intermediate eqs. 2.13 and 2.14. Further experiments were carried out w i t h carbon dioxide (19%) and carbon monoxide (81 %) and m o l y b d e n u m dioxide at roughly 8 0 0 ° C , w h i c h yielded grayish m o l y b d e n u m carbide, presumably according to the reversible eq. 2.14. T h e addition o f carbon dioxide was to prevent build-up o f carbon on the surface, w h i c h was confirmed by  25  the color and the carbon content of the molybdenum carbide [57].  400°C C0  C O + M o O ;'3  + Mo0  2  2  (2.13)  565°C 6CO + 2 M o 0  2  5C0  2  + Mo C  (2.14)  7C0  2  + Mo C  (2.15)  2  565°C 8 C O + 2 M o O'3 ;  2  Hexagonal M o C is the only molybdenum-carbide phase of commercial interest and is 2  the only phase that is stable below 1 1 0 0 ° C [58]. It is produced as a powder in the micron range, with colors varying from white-gray to black [48, 59, 60]. It is stable in hydrogen, but it oxidizes in air above 5 0 0 ° C [48].  2.2.3  Oxidation of molybdenum  Oxidation of molybdenum with oxygen gas Molybdenum retains its luster almost indefinitely in air, particularly when it has been drawn to fine wire. On prolonged heating in air below 6 0 0 ° C , the metal becomes covered with its trioxide; at 6 0 0 ° C the oxide sublimes and rapid oxidation occurs. Molybdenum burns in oxygen at 5 0 0 - 6 0 0 ° C [48].  Oxidation of molybdenum with carbon dioxide Vandenberghe reported that carbon dioxide reacts with molybdenum to form carbon monoxide and molybdenum trioxide above 7 0 0 ° C [61]. Spencer et al. [57] later pointed out that 26  these authors made no analysis o f the solid product, but assumed that the m o l y b d e n u m was o x i d i z e d to m o l y b d e n u m trioxide. The progression of the oxidation was monitored by observations o f the appearance o f the solid phase. T h e colors suggested that the oxidation was carried only to the dioxide, according to eq. 2.16 [57, 61].  700° C  Mo + 2 C 0  M0O2 + 2CO  —  2  (2.16)  Hilpert et al. [62] indicated that at 1 0 0 0 ° C , carbon m o n o x i d e passed over finely d i v i d e d m o l y b d e n u m leads to d i m o l y b d e n u m carbide. A t 8 0 0 ° C they obtained a carbide o f high carbon content by reacting carbon monoxide w i t h m o l y b d e n u m trioxide. S m i t h et al. [63] previously observed no reaction when m o l y b d e n u m was heated to a over 1 0 0 0 ° C  i n an  atmosphere o f carbon monoxide. L i a n et al. [64] demonstrated that at r o o m temperature and at 8 0 ° C , H , N , C H and C O showed no reactivity w i t h m o l y b d e n u m atoms, w h i l e 0 2  and C 0  2  2  4  2  both reacted w i t h m o l y b d e n u m .  T h i n m o l y b d e n u m wire is reported to react w i t h C 0 n  2  between 700 and 1 0 0 0 ° C  for  the formation of C O , and it was concluded to proceed according to eq. 2.8. C h e m i c a l n  conversions o f up to to 8 0 % were reported, over a narrow temperature range, 8 4 0 - 8 6 0 ° C , as illustrated i n figure 2.3. A t 8 2 5 ° C C 0 n  2  decay corrected y i e l d was 3 5 % and decreased  w i t h decreasing temperature, w h i l e at 8 7 5 ° C ,  n  C 0  2  decay corrected y i e l d was 4 5 % and  decreased w i t h increasing temperature.  2.2.4 Interaction of C 0 and CO with Mo C 2  2  M02C is used i n special cemented carbide grades containing T i C and nickel metal. M o s t M o C is used i n steel alloys, where it forms during melting. A l t h o u g h M0O3 or M0O2 2  can be carburized w i t h carbon at 1 5 0 0 ° C , a carbide w i t h the correct carbon content and a  27  90 -  Temperature (*C) R a d i o c h e m i c a l y i e l d , i.e. decay corrected to E O B , from Z e i l s e r et al. [40] Figure 2.3: Decay corrected  n  C O yields as a function o f temperature  l o w o x y g e n content is difficult to obtain. Pure M o C is best made by heating m o l y b d e n u m 2  metal powder w i t h carbon i n hydrogen at 1 5 0 0 ° C [65]. M o l y b d e n u m carbide is also used extensively as a catalyst, such as for aromatization o f ethane, ethylene, propane and i n the oxidative dehydrogenation o f these compounds using carbon dioxide as an oxidant. The catalyst is prepared by heating m o l y b d e n u m trioxide i n a stream o f methane and hydrogen, from 500 to 8 0 0 ° C [54]. D u r i n g preparation, surface contamination by carbon generally occurs. The latter can be removed by treatment w i t h hydrogen under controlled environment. O n c e the excess carbon was completely removed, it was observed that the B E T surface area o f the catalyst and C O chemisorption were highest. F o r a catalyst treated w i t h hydrogen, the surface area was found to be 60 m /g, 2  C O uptake at room temperature o f 220 L e e et al.  u.mol/g  [54].  [54] showed that the m o l y b d e n u m metal has a m u c h lower surface area  than the M o C catalyst. T h e M o C had a B E T surface area o f 60-100 m /g 2  2  with a  2  while T P R  o f M0O3 w i t h hydrogen yielded molybdenum w i t h B E T surface area o f 3 m /g. 2  28  Prior  500  600.  700..  800  900  1000  Temperature [KJ  F r o m S o l y m o s i et al. [66] Figure 2.4: C O formation rate from temperature programmed reaction o f C 0  2  with M o C 2  to removal from the reactor, the d i m o l y b d e n u m carbide was passivated w i t h 1% o x y g e n at room temperature [54].  M o l y b d e n u m can be passivated by oxidation, especially by  electrolytic oxidation, becoming chemically unreactive [48]. Iwasawa et al. [55] observed deposition o f small amounts o f carbon on molybdenum fixed on alumina, after it had been reduced w i t h hydrogen at 5 0 0 ° C for 5 h. S o l y m o s i et al. [66] studied the reaction between carbon dioxide and supported M o C . 2  Temperature programmed reaction o f carbon d i o x i d e w i t h supported M o C forms carbon 2  monoxide, as illustrated i n figure 2.4. C a r b o n monoxide was first detected at 3 0 0 ° C , and a more extensive decomposition o f carbon dioxide to carbon m o n o x i d e occurred above 6 0 0 ° C [66]. U s i n g  1 3  C0  2  as supply gas, it was demonstrated that over 9 0 % o f the C O was  formed from the supply gas and not from the carbide [66]. It was demonstrated that the C O comes mainly from decomposition of C 0 , according to eq. 2.17, and that the contri2  bution o f the reaction o f carbon in M o C w i t h the O atom formed i n the C 0 2  according to eq. 2.18, is limited [66].  29  2  dissociation,  C0 C ) + 0 (8  2  ( a )  ^  C0  ( g )  ^  C0  ( g )  + 0  ( a )  (2.17) (2.18)  The reaction between 2 5 % C 0 and M o C was carried out for several hours at 8 0 0 ° C and 2  2  complete oxidation to M 0 O 3 d i d not occur [66].  2.3  Methanol synthesis  2.3.1 History The history of industrial methanol synthesis covers over three quarters o f a century, w i t h the first barrel o f synthetic methanol produced at B A S F , Germany, i n 1923. The first industrial methanol synthesis process is k n o w n as the high pressure process, w h i c h operated at 250300 bar and 3 2 0 - 4 5 0 ° C , and was the dominant technology for 45 years. T h e feed syngas was based on coal/lignite, w h i c h generally contained a significant amount o f poisons, such as chlorine and sulfur. A c c o r d i n g l y , a relatively poison-resistant catalyst was developed, based on zinc oxide / c h r o m i u m oxide. However, further developments found that copper increased the selectivity to methanol, and that zinc was an efficient dispersant o f copper [67]. The copper based catalyst is quite easily deactivated by poisons found i n coal/lignite, though this problem was overcome by utilizing synthetic gas originating from natural gas and removal of catalyst poisons prior to methanol synthesis. A c c o r d i n g l y , a l o w pressure process was developed in the late 1960's, w h i c h operates at m u c h m i l d e r conditions, i.e. 35-55 bar and 2 0 0 - 3 0 0 ° C . T h e l o w pressure process is still the dominant process being used today [68].  30  2.3.2  Catalyst preparation  M a n y different types of catalysts have been studied, including co-precipitated copper-zinc oxide, co-precipitated copper-zinc oxide alumina, Raney copper, intermetallic compounds and precious metals such as palladium [69]. The current catalysts used i n industrial l o w pressure methanol synthesis are based on copper / zinc oxide / alumina w i t h possible additives such as magnesium oxide [67]. The ratios o f components vary from one manufacturer to another, but typically the copper oxide ranges between 25-80%, zinc oxide between 105 0 % and the alumina between 5-10% [68]. C o m m e r c i a l l y available l o w pressure methanol catalysts have a methanol selectivity above 9 9 % [68]. The l o w pressure catalysts are obtained as metal hydroxycarbonates or nitrates by coprecipitation o f a multi-metal nitrate solution with a solution o f sodium carbonate [70, 71]. Preparation parameters" such as p H , temperature, composition, duration, play an important role in the quality o f the produced catalyst. A typical sequence for co-precipitation is the following:  1. Prepare solution o f zinc, copper and a l u m i n u m nitrates to desired ratio 2. Co-precipitate metal ions using a solution of sodium carbonate 3. Filter metal carbonates and wash with water 4. D r y metal carbonates at 1 2 0 ° C 5. Calcinate the metal carbonates i n air at 3 0 0 - 5 0 0 ° C 6. Pelletize metal oxides 7. Activate the resulting catalyst by reduction in 2 % hydrogen at 250°C  Prior to reduction, the commercial catalysts have a B E T surface area o f 60-100 w h i c h is reduced to 20-30 m /g 2  after reduction [68].  31  m /g, 2  A c t i v a t i o n of freshly prepared industrial catalyst is generally carried out by reduction i n a 1-5% H /N at 1 bar for several hours by ramping up the temperature to 240°C(~30 2  2  °C/h) and holding at this temperature for several hours. T h e reduction o f C u O / Z n O and CuO/ZnO/Al 0 2  3  catalysts, w i t h 2 % hydrogen i n nitrogen at 250°C and 1 bar has been  demonstrated to reduce the C u O to C u metal, v i a the intermediate C u 0 [70]. A t these 2  conditions, the copper oxide is fully reduced to copper metal, without any residual copper oxide remaining [67].  2.3.3  Catalyst poisoning / deactivation  Halogen compounds are k n o w n to poison the copper surface, so methanol feed gas needs to be halogen free [69]. Other impurities in the catalyst itself, such as silicon compounds, nickel carbonyls or iron carbonyls, can cause damage to the catalyst [68]. T h e catalyst can also be deactivated when the reactor is operated i n the absence o f o x i d i z i n g agent such as carbon dioxide [70]. Experiments using a mixture consisting o f only H / C O rapidly 2  and irreversibly deactivated the catalyst [71]. M e t h a n o l yields have been enhanced by the presence o f carbon dioxide, water, and/or oxygen [72]. Experiments performed by pulsing oxygen to a C O / H  2  feed indicated that up to a 15 fold increase o f methanol yields could be  obtained [72]. A c t i v e sites for methanol synthesis can be deactivated when the catalyst is operated for extended periods o f time at elevated temperatures above 2 4 5 ° C [72, 69].  2.3.4  Thermodynamics and kinetics  M e t h a n o l synthesis, typically involves five components: hydrogen, carbon dioxide, carbon monoxide, water and the product methanol. The role of carbon dioxide in the reaction mechanism has been an ongoing debate [73]. U n t i l the early 1980's, mechanistic considerations were based mainly on the reaction between carbon monoxide and hydrogen, illustrated i n eq. 2.19 [68]. T h e higher yields achieved by the addition o f carbon dioxide was attributed to the displacement o f the re32  verse water gas shift equilibrium 2.20. In addition, carbon dioxide was believed to affect the oxidation state of the active sites in the catalyst [70]. Alternatively, it was proposed that methanol was formed uniquely due to the reaction of hydrogen and carbon dioxide, illustrated in eq. 2.21 [74]. Recent experiments with isotope labelled reactants showed that both reactions 2.19 and 2.21 are possible [68].  CO + 2 H  2  ^  CH OH  (2.19)  C0 + H  2  ^  H 0 + CO  (2.20)  2  ^  CH OH + H 0  2  C 0 + 3H 2  3  2  3  2  (2.21)  Reaction enthalpies can be determined from the standard enthalpies of the reactants and products, and are -91 kJ/mol for eq. 2.19, -49 kJ/mol for eq. 2.21. Both reactions for methanol synthesis are exothermic and consequently methanol synthesis is favored by low temperature and high pressure. Additionally, the reaction of carbon dioxide with hydrogen, know as the reverse water-gas shift reaction, shown in eq. 2.20, must be taken into account. The enthalpy for the reverse water-gas shift reaction, is 41 kJ/mol. Consequently, this endothermic reaction is favored by high temperatures and low pressure.  33  Chapter 3 Experimental: Trapping and purification of CC>2 n  The key intermediate i n the radiosynthesis o f many carbon-11 radiopharmaceuticals is [ C]methanol. n  This study focuses on the feasibility o f a gas phase methanol synthesis,  the optimization o f the main steps involved and it's applicability to the radiosynthesis o f [ C ] m e t h a n o l . The three principal steps evaluated i n this study include: n  1. Trapping and purification o f [ C ] c a r b o n dioxide n  2. Conversion o f carbon dioxide to carbon monoxide using m o l y b d e n u m 3. M e t h a n o l synthesis from carbon monoxide and hydrogen over a copper zinc oxide catalyst  3.1  Introduction  The C02 is produced in a cyclotron and subsequently concentrated i n a carbon molecular U  sieve trap.  The effect o f temperature and mass o f carbon molecular sieves on the trap  performance was examined by computing the trapping efficiency, illustrated i n eq. 2.4. The  34  overall trapping efficiency, illustrated i n eq. 2.6, is based on the irradiation conditions for production o f carbon-11 (proton current, proton energy, irradiation time) and on trapping data (amount  n  C 0  not trapped, amount o f C 0 n  2  2  released from trap and time required).  3.2 Materials and methods Irradiations were performed w i t h the E b c o Technologies T R I 9 cyclotron o f the C H U S P E T facilities, Sherbrooke, Q C . Capintec dose calibrators where used for quantitative measurement o f carbon-11. T h e target used is an E b c o Technologies gas target, consisting o f a water-cooled a l u m i n u m cylindrical body, w h i c h contains the target gas. T w o Havar w i n dows, w h i c h separate the high pressure gas target from the high vacuum cyclotron, are cooled w i t h h e l i u m . A trap was designed such that it could be cooled to -20° C and rapidly heated to 110°C. T h e prototype trap was built at E b c o Technologies. Thermo-electric coolers ( T E C ' s ) were selected for their ability to be remotely controlled by computer and their relatively rapid cooling time. They have the advantage over conventional cryogenic traps that no l i q u i d n i trogen is required and thus no m o v i n g parts are necessary. T h e T E C ' s require a D C voltage input, therefore the trap c o o l i n g can be remotely controlled by computer. T h i s increases the level o f automation i n the final synthesis module and enables repeated productions w i t h out having to access the unit. To provide fast heating, a 325 W  cartridge heater were  used, c o m b i n e d with the T E C ' s operated i n reverse mode, w h i c h provided an additional 100 W heating power. The final trap design implemented consisted of a copper b l o c k , through w h i c h a U shape was machined and onto w h i c h two 35 m m long 6.35 m m outer diameter copper tubes were brazed. T h e U shape trap was then packed with carbon molecular sieve (Carbosphere 60-80 mesh) and both ends were plugged with quartz w o o l . A d d i t i o n a l l y , a 6.35 m m  diameter  hole was bored through the copper block, i n w h i c h the 325 W cartridge heater was placed.  35  A K - t y p e thermocouple was mounted on the copper trap to monitor temperature and allow temperature control. The copper b l o c k was screwed onto an a l u m i n u m heat sink block, w i t h 2 thermo-electric coolers ( T E C ' s ) placed in between. A hole was drilled through the a l u m i n u m b l o c k and connected to a supply o f c o o l i n g water, to remove the heat generated by the T E C ' s during the c o o l i n g step. After trap assembly, the carbospheres where conditioned by heating to 2 5 0 ° C and under flow o f h e l i u m for 2 hours. Nitrogen/oxygen ( U H P 9 9 . 5 % N , 0.5% 0 ) for the production of carbon-11 and h e l i u m ( H e l i u m U H P ) were 2  2  available on site at the C H U S facilities. The temperature was controlled by a manual thermostat, obtained from Omega.  The  flow rate of the helium sweep gas was controlled by a mass flow controller, obtained from M K S . The mass flow controller was calibrated using the soap bubble method, for w h i c h calibration curves are illustrated on page 91. S o l e n o i d valves, 2-way normally closed, were obtained from Precision D y n a m i c s . A check valve, w i t h cracking pressure o f 0.3  bar,  was obtained from Swagelok. A control panel, to enable remote control o f valves, reactor temperature and mass flow controller was built by E b c o Technologies.  3.3  Experimental set-up  Figure 3.1 illustrates the experimental setup used to determine the trapping efficiencies. The [ C ] c a r b o n dioxide trap, the solenoid valve for helium gas supply, the mass flow n  control valve for helium flow control, the check valve and Ascarite c o l u m n were located i n a lead shielded hot c e l l . The cyclotron was located i n a concrete shielded vault. The target was installed on the cyclotron target selector, w h i c h is locally shielded.  3.4  Experimental procedure  The trapping efficiencies o f a copper tubular trap, w i t h 4 different amounts o f carbon molecular sieves, were measured w i t h the experimental configuration illustrated i n figure 3.1, for 36  99.5% N. 0.5% O 2  Protons 15.4 MeV  Alphas  *| Target N , a,,  1  2  0)  SV2  He  O SV3 MFC  Dose Calibrator Fume Hood Figure 3.1: C 0  Trapping experimental flow diagram  n  2  temperatures varying from -20° C to 1 0 0 ° C . The experimental procedure can be separated in to two distinct majors steps; production o f C 0 n  2  and  1 1  C 0 trapping, purification and 2  release.  3.4.1  Production of  U  C0  2  [ C ] C a r b o n dioxide was produced by proton irradiation o f the nitrogen/oxygen filled gas n  target. T h e gas target and all valves to control the  filling/unloading  were already i n place  at the C H U S P E T facilities. Thus the target loading and unloading were done using the current setup implemented at C H U S for [ C ] a c e t a t e production, w i t h the unload line ren  plumbed to connect it to the experimental setup located i n the hot c e l l . T h e 22 cm  3  ( S T P ) target was filled to 17 bar.  O n c e the cyclotron was i n operation at  a few U.A, the target was positioned so that at least 8 0 % o f the beam bombarded the target. T h e current was then increased to approximately 10 u-A, w h i l e monitoring the target pressure, ensuring that it d i d not exceed 25 bar.  A saturated y i e l d o f C - l l is produced  in roughly 40 min o f bombardment. However, for these tests, only small amounts o f radioactivity were desired, m a i n l y to keep exposure to radiation below allowable levels set by Health Canada. Consequently 10 m i n o f bombardment was sufficient. T h e cyclotron energy was not modified, and remained at the preset value o f 15.4 M e V . D u e to energy drop across the Havar foils, the beam energy that actually irradiates the target gas was about 37  14  MeV. Several control runs were performed in order to determine the y i e l d o f the target. T h e  target was irradiated as above, and its contents were directly emptied i n an Ascarite trap l o cated i n the Capintec dose calibrator. T h i s allows measurement o f total amount o f [ ] C 0 n  2  produced i n target as a function o f irradiation conditions, namely beam intensity and irradiation duration. Ten control runs were performed and the target y i e l d was determined using eq. 2.3. F o r subsequent experiments, the amount o f C 0 n  2  produced i n target was c o m -  puted based on the target y i e l d , proton beam intensity and an irradiation duration, using eq. 2.3. The steps involved i n the production o f C 0 n  2  are the f o l l o w i n g :  1. T u r n on cyclotron (Ion source, main magnet, vacuum, utilities, target w i n d o w c o o l ing, target c o o l i n g , R F ) 2. O p e n the main valve on the nitrogen/oxygen gas cylinder 3. Set the pressure regulator to read 17 bar 4. O p e n the target valve 5. C l o s e the target valve once pressure sensor read-back is roughly 17 bar 6. Set the N / 0 2  2  pressure regulator to 8 bar(for target rinse)  7. R e m o v e ion beam stop ( I B S ) (now beam w i l l be on target)  8. Adjust cyclotron main magnet  9. Adjust position o f target  10. Increase proton beam to 10 u.A  11. Irradiate for 10 min  38  3.4.2  Trapping and release of  Prior to production o f the were turned on.  N  C02  C 0 , the trap water c o o l i n g valve was opened and the T E C ' s  n  2  A stable trap temperature o f - 2 0 ° C was reached i n less than 10 min.  The target gas was unloaded through the pre-cooled trap and rinsed w i t h 8 bar mixture. The trap was then rinsed w i t h U H P H e at flow-rates up to 70 cm trap was closed and heated to 1 1 0 ° C . T h e  n  C 0  2  3  N /0 2  2  ( S T P ) . The  was released w i t h a stream o f H e and  then trapped i n a sodium hydroxide c o l u m n . The sodium hydroxide c o l u m n was placed i n a dose calibrator, to allow continuous measurement o f C 0 . T h i s enabled quantification n  2  of the amount o f C 0 n  2  not trapped by the trap, and also the amount released from the  trap. These quantities were decay corrected to end o f the bombardment ( E O B ) (eq. 2.2), to enable determination of the overall trapping efficiency (eq. 2.5). In order to ensure that no activity remains on the trap, it was disassembled and placed i n the dose calibrator. The steps involved i n the C 0 n  2  trapping and releasing are the f o l l o w i n g :  1. Turn on c o o l i n g water and T E C 2. O p e n valve on h e l i u m gas cylinder and set regulator to 2 bar 3. Set mass flow-control valve to desired set point 4. Place a fresh sodium hydroxide c o l u m n i n dose calibrator 5. O p e n valve to unload target 6. M a k e sure target pressure is below 8 bar  7. O p e n valves on carbon molecular sieve trap  8. Measure amount o f C 0 n  2  breakthrough throughout unloading step  9. C l o s e valve to unload target  10. O p e n valve to fill target w i t h N / 0 2  2  to rinse target and close after 10 s 39  11. O p e n valve to unload target 12. W h e n the target pressure is ~ atmospheric, close a l l valves 13. O p e n H e l i u m supply valve to rinse trap for 30 s 14. Heat trap (until release temperature is reached) 15. F l u s h h e l i u m through c o l d trap 16. Note radioactivity reading every 15 s  3.5 Results and discussion T h e target y i e l d was determined to be 83 ± 4 m C i / u . A , for an extracted beam energy o f 15.4 M e V and energy on target o f approximately 14 M e V . A s can be seen i n table 3.1, this value is lower than other reported experimental and theoretical yields. T h e target was subsequently redesigned to give a y i e l d o f about 150 m C i / u A . Table 3.1: C - l l target yields, 14 M e V Yield (mCi/^A) Target E b c o improved target  150  E b c o target  83 ± 4  Vandewalle et al.[32]  135 ± 7  Casella e t a l . [30]  92  Theoretical yield[31]  169  The time required for each step o f the trapping sequence was determined i n a systematic fashion. T h e unload time was set to 30 s since at that time the pressure i n the target had dropped to nearly atmospheric. T h e time required for the rinse target step was set to 15 s, corresponding to the time required to manually perform the sequence of valve actuation. T h e time for the second target unload was determined by monitoring the radioactivity c o l lected i n an Ascarite c o l u m n , w i t h the C 0 n  2  trap bypassed. A m a x i m u m value was seen  after 45 s. A d d i t i o n a l runs were done with 2 target rinses, however no significant amount 40  Table 3.2:  U  C0  trapping/releasing Sequence  2  Step  Description  T i m e elapsed (min:s)  1  U n l o a d target ( E O B )  0:00  2  Rinse target  0:30  3  U n l o a d target  0:45  4  H e R i n s e trap  1:30  5  Heat trap  2:00  6  Release  n  C 0  2:30  2  Table 3.3: C 0 trapping efficiencies Carbosphere (g) Trapping efficiency ( ± S T D E V ) n  2  Trap 1  1.0  2 5 % ± 2 % (n=4)  2  1.3  4 5 % ± 2 % (n=4)  3  1.9  92% ± l%(n=4)  4  2.8  99% ± l%'(n=4)  of additional C-11 was recovered. T h e H e rinse of the trap was set to 30 s, to allow sufficient time to remove the target gas from the trap [34]. The time for heating the trap to 110°C was 30 s. Table 3.2 illustrates the final sequence used, w i t h the time (from E O B ) at w h i c h each step was executed.  3.5.1  Effect of carbon molecular sieve mass on C 0 n  2  trapping effi-  ciency T h e amount o f carbon molecular sieves necessary for optimal trapping was determined by comparing the trapping efficiencies for different amounts o f carbon molecular sieves. T h e pre-cooled trap temperature was typically -20° C  and the amount of 60-100 mesh  carbon molecular sieves, was varied from 1.2 g to 2.8 g . Table 3.3 illustrates the trapping efficiencies for four different amounts o f carbon molecular sieve. A s the amount o f carbon molecular sieves increases, the trapping efficiency increases. However, w i t h increasing amount o f carbon molecular sieves, the time required for recovery w i l l l i k e l y increase and the volume in w h i c h the C 0 n  2  n  C 0  2  is delivered to downstream  process may be larger. Thus the amount o f carbon molecular sieves used for subsequent 41  — T = 100 °C ^ - T = 20°G -«-T.= -20 °C  300  .  ^  '  t  0:00  '— i  0:30  1:00  .  ,  .  1:30  ,  .  2:00  1  ,  ,  2:30  3:00  3:30  4 4:00  Elapsed time, from E'OB (min) Figure 3.2:  1 1  C0  2  activity vs. time, for different trap temperatures.  experiments was set to 2.0 g , i.e. the lowest amount required to obtain above 9 5 % trapping efficiencies. The optimal amount w i l l vary w i t h target volume, target pressure, length and size of tubing from the target to the trap and trapping temperature.  3.5.2 Effect of trap temperature on CO2 trapping efficiency The temperature required for optimal trapping was determined by comparing the trapping characteristics at different trapping temperatures. T h e trap temperature was kept constant for each run, and the sequence shown i n table 3.2 was used, w i t h steps 5 and 6 omitted. Thus, the H e rinse step was continued until 10 minutes E O B . F i g u r e 3.2 illustrates the effect o f temperature on the retention o f  1 1  C 0 2 i n the trap. A t 1 0 0 ° C , the trap d i d not retain  any significant amount o f C 0 . A t r o o m temperature, there was a slight delay before the n  2  activity was seen i n the ascarite c o l u m n . A t - 2 0 ° C , the activity remains on the trap even after 10 minutes E O B . T h e initial amount o f C 0 n  each case.  42  2  at E O B was approximately 250 m C i in  Table 3.4: C o m p a r i s o n o f overall trapping efficiency O v e r a l l trapping efficiency Trap C r y o g e n i c [13, 35]  76-84%  M o l e c u l a r sieve 1 3 x [ l 3 ]  74%  C a r b o n molecular sieve[34]  83%  Carbon molecular sieve (this work)  88% ± 2 %  3.5.3  Overall trapping efficiency  F o r a trapping efficiency o f 9 9 % obtained using 2.8 g carbon molecular sieve at - 2 0 ° C , the time required to deliver the  n  C 0  2  was 3.5 minutes. T h i s corresponds to an overall  trapping efficiency of 8 8 % , w h i c h is competitive w i t h reported results (see table 3.4). T h i s w o u l d be sufficient for incorporating into a system for routine production o f carbon-11 radiopharmaceuticals.  43  Chapter 4 Experimental: Reduction of CO2 to CO 4.1  Introduction  T h e f o l l o w i n g step i n the overall process for n  n  C 0  C H O H preparation is the reduction o f 3  to C O . Y i e l d s up to 8 0 % were reported at 8 5 0 ° C n  2  1 1  for the reduction o f C 0 n  2  to  C O using m o l y b d e n u m [1], as described i n section 2.1.3. N o special treatment to the  m o l y b d e n u m was done prior to reaction, and the reaction proceeds by direct oxidation o f m o l y b d e n u m to m o l y b d e n u m dioxide as shown i n eq. 2.8 [75].  4.2  Preliminary experiments: reaction of C 0 2 and Mo n  Preliminary experiments for the reduction o f carbon d i o x i d e were performed at the C H U S P E T facilities, Sherbrooke, Q C , using  4.2.1  Materials and methods  The C 0  2  n  n  C0 . 2  was produced and purified using procedure described i n Chapter 3 on page 34.  T h e carbon dioxide/carbon monoxide reactor consisted o f a 9.5 m m outer diameter c y l i n drical quartz tube w i t h 6 m m inner diameter, packed uniformly w i t h 2.3 g o f m o l y b d e n u m  44  wire, 0.05 mm diameter and 500 m (Goodfellow C o r p ) . T h e quartz tube was horizontally mounted i n a 400 W ceramic tubular heater (Omega). The temperature was measured w i t h a K - t y p e thermocouple (Omega) and controlled with a manual thermostat (Omega). A mass flow controller, obtained from M K S , was used to control the flow rate o f the h e l i u m sweep gas.  It was calibrated by varying the input voltage from 0-5 V , and the  output flow o f h e l i u m was measured using the soap-bubble technique. T h e flowrates were corrected to S T P using the ideal gas law. The resulting calibration curve is illustrated on page 92. S o l e n o i d valves, 2-way normally closed, were obtained from P r e c i s i o n D y n a m i c s . A control panel, to enable remote control operation o f valves, reactor temperature and mass flow controller, was built by E b c o .  4.2.2 Experimental set-up T h e flow diagram for the experiments using C 0  is illustrated i n figure 4.1. T h e same  n  2  set-up was used as described i n section 3.3 for production and release o f C 0 . n  2  m o l y b d e n u m reactor was added to the outlet o f the  n  C 0  2  The  trap, followed by an Ascarite  ( A l d r i c h ) trap and a silica ( A l d r i c h ) trap, w h i c h was c o o l e d with l i q u i d nitrogen. A t the outlet o f the reactor, a solenoid valve was placed to avoid exposure to atmosphere.  The  setup was located i n a lead shielded hot c e l l , w i t h all valves / flowmeter controlled remotely.  99.5% N . 0.5% Q , SV1)  Protons  Alpha as  Target  15.4 MeV  11  N^.O^'.CO,  I  SV2  He  c v 1  j-X—t&H !SV3 MFC  1  co  SV4 2  Trap  Mo Reactor  He, N „ 0 .  ^  > 8 1 ,  Fume Hood  n  C 0  2  Reduction experimental flow diagram  45  C/3  CD He. CO  Figure 4.1:  He  He.1 " C 0 „ " C 0 ,  SV5 fx3———-2  Dose Calibrator ;  4.2.3  Experimental procedure  The production of C 0  was carried out as i n the C 0  n  n  2  2  trapping experiments, described  i n section 3.4.1. T h e irradiation condition were noted to enable quantification o f the total amount o f C 0 n  produced i n target. The C 0  trap was conditioned by flowing h e l i u m  n  2  2  at 250°C for 2 h . Initial experiments were carried out with m o l y b d e n u m as-supplied. Subsequently, experiments where carried out after pre-reducing the m o l y b d e n u m with 10 % hydrogen i n helium at 850°C. T h e silica gel trap was initially conditioned by heating to 650°C w h i l e purging w i t h helium. T h e molybdenum oven was preheated to 800, 850, 900 and 950°C, under flow o f helium. T h e C 0  was released from the  n  2  n  C 0  2  trap at 17.5,  35 and 70 cm /min ( S T P ) helium, through the m o l y b d e n u m reactor, the Ascarite c o l u m n 3  and the silica c o l u m n submerged i n l i q u i d nitrogen. T h e c o l d silica c o l u m n was placed i n the dose calibrator to measure the amount o f C O . W h e n the activity on the silica c o l u  umn reached a m a x i m u m , the amount o f C 0 n  2  on the Ascarite was likewise measured by  placing the c o l u m n i n the dose calibrator. This enabled quantification o f the amount o f unreacted C 0 n  2  that had been released from the reactor. To m i n i m i z e exposure to radiation,  long thongs were used to place the Ascarite trap i n the dose calibrator. T h e decay corrected conversion o f C 0 n  2  to  C O was computed based on the amount o f activity produced i n  1 1  target and the amount o f C O measured. Table 4.1 illustrates the sequence that was used, n  with the time from E O B at w h i c h each step was executed.  4.2.4  Results and discussion  Initial experiments resulted i n C 0 n  conversion to C O of about 5%. A t the end o f the u  2  experiments, it was observed that the molybdenum surface was no longer a shiny metallic color but a dull grayish color. Since the industrial compound M o 0  3  is described as a gray-  green powder [48], it was suspected that the m o l y b d e n u m was oxidized. M o l y b d e n u m metal powder is produced industrially by reducing compounds such as M 0 O 3 powder w i t h 46  Table 4.1: C 0  R e d u c t i o n sequence T i m e elapsed (min:s) Description U  Step  2  1  U n l o a d target ( E O B )  0:00  2  Rinse target  0:30  3  U n l o a d target  0:45  4  H e rinse trap  1:30  5  Heat trap  2:00  6  Release  U  C0  2:30  2  7  1 1  C O measurement  6:30  8  1 1  C0  7:30  2  measurement  Table 4.2: Summary o f C O yields, 17.5-70 cm /min, 2 bar T ( ° C ) Y i e l d (decay corrected) S . D . n  3  800  6%  2%  850  8%  2%  900  9%  4%  950  8%  2%  hydrogen between 5 0 0 - 1 1 5 0 ° C [49]. In order to reduce the m o l y b d e n u m trioxide back to the metallic state, 10% hydrogen i n argon was flowed through the reactor at 8 5 0 ° C , for 30 min. Thereafter, experiments were resumed. D e c a y corrected yields were calculated based on eq. 2.2. T h e amount o f [ C ] c a r b o n dioxide produced i n the target at the end o f n  bombardment was computed using eq. 2.3, based o n the target y i e l d (see table 3.1), beam current and irradiation duration. A summary o f the decay corrected yields obtained during hot experiments are given i n table 4.2. F o r each temperature tested, at h e l i u m flow rates o f 17.5, 35 and 70 cm /min ( S T P ) , the average conversion o f C 0 3  n  to C O was at most 9%. n  2  Based on these results, there is no apparent correlation between flow and/or temperature with conversion. Conversion i n the order o f 8 0 % was expected based on published data [40]. After completing the hot experiments, the m o l y b d e n u m was again a dull grayish color indicating that oxidation may have occured. It is suspected that the helium flush o f the n  C 0  the  n  2  trap was insufficient, and that some o f the oxygen from the target gas remained i n  C 0  trap. W h e n attempting to reduce the C 0 U  2  47  2  w i t h the m o l y b d e n u m reactor, the  residual oxygen may have o x i d i z e d the m o l y b d e n u m . M o l y b d e n u m retains its luster almost indefinitely i n air, particularly when it has been drawn to fine wire. However, when heated in air, oxidation occurs and renders the surface chemically unreactive [48]. Consequently, for future use it is recommended to ensure that a l l oxygen is removed from the C 0  trap.  n  T h i s can be practically implemented by flowing additional h e l i u m through the at room temperature or during the heating step, prior to C 0 n  2  n  2  C 0  2  trap  desorption.  Another interesting observation is that on average, only 5 3 % of the C - l 1 was accounted for during runs performed immediately after reduction o f the m o l y b d e n u m . U s i n g a hand held Geiger counter, most o f the unaccounted for carbon-11 was found to be on the m o l y b denum reactor. F o r subsequent runs (i.e. not immediately after reduction), an average o f 96% o f the expected carbon-11 was recovered from the reactor. It appears that freshly reduced m o l y b d e n u m either reacts w i t h carbon oxides or that carbon oxides remain adsorbed on the surface. Clearly the state o f the m o l y b d e n u m plays an important role i n the reduction o f carbon dioxide to carbon monoxide. To gain a better understanding o f surface pretreatment and the effect o f flow and temperature on C 0 reduction by m o l y b d e n u m , further experiments were 2  carried out w i t h c o l d  1 2  C0  2  at U B C . In parallel to these experiments, a study o f equilibrium  using A s p e n was carried out for various systems containing m o l y b d e n u m , m o l y b d e n u m oxides, m o l y b d e n u m carbides, oxygen, hydrogen, carbon, carbon oxides and water.  4.3  Equilibrium computer simulations of systems containing molybdenum  E q u i l i b r i u m o f m o l y b d e n u m oxidation w i t h oxygen and m o l y b d e n u m trioxide reduction with hydrogen reduction were examined, as was the e q u i l i b r i u m o f m o l y b d e n u m oxidation w i t h carbon dioxide using a process simulator. T w o process simulators were available i n the Department o f C h e m i c a l & B i o l o g i c a l Engineering; A s p e n [76] and H y s y s [77]. A s p e n was  48  selected due to it's broad component database w h i c h includes solids such as m o l y b d e n u m . In order to obtain e q u i l i b r i u m data, a G i b b s reactor was setup using A s p e n . A l l relevant components available from the database were included for each simulation. U s i n g the sensitivity study feature o f A s p e n , e q u i l i b r i u m data was generated for a w i d e range o f temperatures. Further details about setting up the A s p e n simulations are described i n the appendix, on page 100. A good overall agreement between A s p e n produced simulation data with published e q u i l i b r i u m data for the system containing M o , C H , C , H and M o C 4  2  2  is demonstrated.  4.3.1  Reduction of M0O3 with H  2  A s p e n generated e q u i l i b r i u m data for the system containing H , 0 , H 0 , M 0 O 3 , M o 0 , 2  2  2  2  M o O and M o is presented i n figure 4.2, based on an initial H : M 0 O 3 ratio o f 15:1, and at 2  atmospheric pressure. M o 0  3  is reduced to M o 0  2  at r o o m temperature. A t 800 K , M o 0  2  begins to form M o , until it is completely reduced at - 1 0 0 0 K . B a s e d on simulation results, it appears that the reduction of M o 0  3  to M o proceeds through two reactions, v i a the  intermediate m o l y b d e n u m d i o x i d e , as shown i n eqs. 4.2 and 4.3. In practice, a large excess of H w i l l be present, since a continuous stream o f hydrogen 2  w o u l d flow over a fixed amount o f m o l y b d e n u m . Figure 4.3 illustrates the effect o f increasing the amount o f Ff from stoichiometric feed amounts (for complete reduction according 2  to eq. 4.1) up to an excess with H : M 0 O 3 molar ratio o f 240:1. The effect o f increas2  ing the excess o f hydrogen is to shift the e q u i l i b r i u m to metallic m o l y b d e n u m at a lower temperature.  3H + M0O3  —  Mo + 3 H 0  (4.1)  H + M0O3  —  Mo0 + H 0 2  (4.2)  —  Mo + 2 H 0  (4.3)  2  2  2H + M o 0 2  2  49  2  2  2  1500  900  Temperature (K) -MO  -H2  — -MOO  02  Initial ratio of H : M 0 O 3 o f 15:1, at atmospheric pressure 2  Figure 4.2: E q u i l i b r i u m compositions o f M0-M0O-M0O2-M0O3-H2-O2-H2O from 300 to 1500 K  4.3.2  Oxidation of Mo with 0  2  Equilibrium of oxygen and molybdenum U s i n g the same component database and G i b b s reactor as for M 0 O 3 reduction, equilibrium data for M o oxidation was obtained. T h e data generated from A s p e n indicates that M o would be completely oxidized to M 0 O 3 , as illustrated i n eq. 4.4, at temperatures above 273 K , for stoichiometric and larger amounts o f 0 . 2  30  2  + 2Mo  -*  2Mo0  (4.4)  3  Equilibrium of carbon dioxide and molybdenum S i m i l a r to above, simulations were carried out using A s p e n to obtain equilibrium curves to better understand the effect of temperature on interaction between M o and C 0 . T o cover 2  all possible reactions, the components added to the simulation were the f o l l o w i n g : H e , A r , 50  300  500  ?00  900  1,100  1,300  1.500.  Temperature (K)  H , : M o O , Ratio  |  240:1  60:1.  15:1  Figure 4.3: E q u i l i b r i u m mole fraction of M o 0  2  7.5:1  -iiT]  for different H : M o 0 2  3  ratios from 300 to  1500K C O , C 0 , C , M o , M o O , M o 0 , M 0 O 3 , M o C and M o C . T h e gas feed stream was set to 2  2  contain 50 p p m C 0  2  2  i n argon, w i t h an excess m o l y b d e n u m , at atmospheric pressure. T h e  resulting data is illustrated i n figure 4.4. T h e compounds present at e q u i l i b r i u m are M o , C O , C 0 , M o C , M o 0 . Three distinct stages can be observed. Between 500 K and 800 2  2  2  K , equimolar amount o f M o 0  and M o C are formed, most probably according to eq. 4.5,  2  2  and no carbon is present i n the form of carbon oxides. A s the temperature increases above 800 K , the amount o f M o C relative to M o 0 2  2  decreases, until no M o C is present at 910 2  K . A t this point the amount o f C O is the highest, corresponding to 7 3 % conversion o f C 0 . 2  A b o v e 910 K , it appears that the reaction proceeds according to eq. 4.6.  C0  + 3Mo  2  2C0  2  + Mo  Mo C + Mo0 2  _>  2CO + M o 0  2  2  (4.5) (4.6)  To verify these reactions independently, A s p e n simulations were carried out for the  51  1.0  500  BOO  700  BOO  1000  900  1100  1200  1300  1400  1500  T(K) j  C02  CO  MO  -MOQ2  -  M02C  |  Figure 4.4: E q u i l i b r i u m o f composition o f M o - M o 0 - M o C - C 0 - C O 2  2  2  same components as above, but using an e q u i l i b r i u m reactor, for w h i c h the chemical reaction can be specified. The feed gas stream was set to contain 50 p p m C 0  2  i n argon,  with an excess m o l y b d e n u m i n the solid feed stream, both at atmospheric pressure. F o r an e q u i l i b r i u m reactor based on eq. 4.5 only, the resulting equilibrium curve is illustrated in figure 4.5. F o r temperatures below 800 K , no carbon dioxide is present, the only c o m pounds present are d i m o l y b d e n u m carbide and molybdenum dioxide, w h i c h confirms that the lower temperature plateau i n figure 4.4 proceeds according to eq. 4.5. F o r an equilibrium reactor based on eq. 4.6, the resulting equilibrium curve is illustrated i n figure 4.6. A t 500 K , carbon monoxide is present w i t h a molar fraction just below 0.90. A s temperature increases, the molar fraction o f carbon monoxide gradually decreases to 0.66 at 1500 K . The high temperature plateau i n figure 4.4 follows the same exponential decrease, w h i c h confirm that the high temperature stage proceeds according to eq. 4.6. Further simulations were carried out to explore the effect o f varying the C 0  2  concen-  tration on the e q u i l i b r i u m amounts o f C O present, as represented i n figure 4.7. T h e equil i b r i u m data is represented in terms o f conversion o f C 0  52  2  to C O , w h i c h was calculated by  Figure 4.5: Equilibrium molar fraction of CO2 from eqs. 4.5  1.00 0.90 0.80 0.70  c  0:60  ati  0 0  0 50  0  :  LL U 0 40 O  S  0.30 0.20 0.10  500  700  900  1100  1300  1500  Temperature (K)  Figure 4.6: Equilibrium molar fraction of CO from eqs. 4.6  53  80%  Q70%  5  r  ™  60%  :  ^40%  I  J  j$ 10% 0% 500  i  I I 1  1 ppm C 0 2  Figure 4.7: Conversion o f C 0  1100  T(K)  1% C02  2  /  /  900  700  ;  !  /  0 20%  /  ;  i  c30% o  /  ,<  j  §50%  /  1500  1300 50 ppm  10% CQ2  to C O vs. temperature for different C 0  2  concentration,  based on A s p e n e q u i l i b r i u m data d i v i d i n g the e q u i l i b r i u m amount o f C O by the initial amount o f C 0 . T h e shape o f the 2  curve follows a similar pattern for each C 0  2  concentration.  above are present i n all cases. T h e temperature at w h i c h C 0  The three stages described 2  conversion reaches a m a x i -  m u m increases w i t h increasing carbon dioxide concentration. F o r 1 p p m carbon d i o x i d e , the m a x i m u m C 0 c o n v e r s i o n to C O occurs at 850 K , w h i l e for 10% carbon d i o x i d e the 2  m a x i m u m conversion occurs at 1250 K . C o l d experiments were performed w i t h 50 p p m carbon dioxide. A c c o r d i n g l y , the experimental temperature range was selected to cover the three stages described above, i.e. from 600 to 1150 K .  4.4 Cold experiments: reaction of CO2 and Mo 4.4.1 Introduction C H U S "hot" testing facilities provide a relatively simple method to quantify conversion o f trace amounts o f C 0 . n  2  However, due to limited availability o f the C H U S facilities and  the financial burden associated with their use, " c o l d " testing with non-radioactive C 0  54  2  was  done to better understand the factors affecting the reduction of C 0  2  with molybdenum.  Temperature programed reduction o f carbon dioxide w i t h m o l y b d e n u m and the effect o f flow rate on the reduction o f carbon dioxide with m o l y b d e n u m were studied.  4.4.2  Materials and methods  D u r i n g typical productions o f carbon-11 compounds, the concentration o f C 0 ranges from 2  1-2000 p p m i n the feed gas, as demonstrated i n the appendices on page 105. A 50 p p m C0  2  feed gas was selected, consisting o f certified 51.4 p p m C 0  contained i n a 100 bar  2  i n h e l i u m , w h i c h was  standard laboratory size gas cylinder.  The gas flow rate was controlled by a mass flow controller ( M K S instruments) for flow rates below 70  cm /min ( S T P ) and by an adjustable needle valve correlated 3  (Cole-Parmer) for higher  flowrates.  flowmeter  C a l i b r a t i o n o f both flow control devices was done  using the soap-bubble method, and calibration curves are included in the appendices, on page 91. M a n u a l 2-way valves (Swagelok) were placed at the inlet and at the outlet o f the reactor. T h e reactor consisted o f a 400 W ceramic tubular heater (Omega Heating) i n w h i c h a glass tube was placed, w h i c h contained 2.3 g m o l y b d e n u m wire previously described, covering a length o f 10 cm. A K - t y p e thermocouple was placed i n the m i d d l e o f the ceramic heater, and a second K - t y p e thermocouple was place inside the reactor, on the m o l y b d e n u m wire. Temperature was controlled w i t h a manual operated thermostat (Omega). T h e temperature profile along the reactor was obtained by measuring the temperature at 2 c m intervals from the entrance o f the reactor. Temperature profile o f the reactor showed a variation o f over 1 6 0 ° C over the m o l y b d e n u m covered length o f the reactor for a setpoint o f 7 4 0 ° C , as illustrated in the appendices, on page 98. T h e addition o f quartz w o o l plugs on either end o f the ceramic heater improved the temperature profile along the reactor, reducing the temperature variation of the molybdenum covered length to less than 6 0 ° C . T h e product gas stream was connected to a 6-port sampling valve ( V I C I ) . T h e 6-port  55  valve was also connected to a waste stream, to a 2 cm ( S T P ) sample l o o p , to a hydrogen 3  supply and to the the inlet o f the gas chromatograph. A Varian 3600 gas chromatograph was used, equipped w i t h a a flame ionization detector ( F I D ) . T h e c o l u m n used on the gas chromatograph was a 3 m l o n g , 3.2 mm outer diameter c o l u m n , packed w i t h 60-80 mesh carbon molecular sieve. F I D detectors are not very sensitive to carbon monoxide, and are not useful for detection of carbon dioxide. A w e l l k n o w n method o f analyzing trace amounts o f carbon oxides using F I D is to first convert the oxides to methane using a nickel catalyst. Near quantitative conversion o f carbon monoxide and carbon d i o x i d e to methane can be accomplished by flowing the sample gas containing the carbon oxides over a nickel catalyst w i t h excess hydrogen, at 3 7 0 - 4 5 0 ° C . A c c o r d i n g l y , a methanizer was built. A 15 cm l o n g a l u m i n u m heater b l o c k was built at E b c o to a c c o m modate a 6.3 mm diameter 175 W cartridge heater (Omega), a 3.2 mm diameter tube and a 1.6 mm diameter K - t y p e thermocouple (Omega). A 3.2 mm diameter stainless steel tube was packed w i t h 0.34 g o f a mixture o f 15% c o m m e r c i a l l y available nickel on alumina powder (< 60 u.m) and 8 5 % activated alumina, 100-120 mesh size. The excess nickel powder was shaken off prior to p a c k i n g the tube, after w h i c h quartz w o o l plugs were placed at both ends o f the tube. The nickel packed tube was placed i n the a l u m i n u m heating block. Swagelok fittings were placed on either end of the tube. T h e methanizer was placed i n the gas chromatograph, i n between the separation c o l u m n and the flame ionization detector. T h e temperature was controlled w i t h a manual thermostat (Omega). Calibration curves for carbon monoxide and carbon dioxide are given in the appendices, on page 93.  4.4.3  Experimental set-up  T h e flow diagram for the experimental setup used for the reduction o f C 0 trated i n figure 4.8.  56  2  to C O is i l l u s -  He/C0 /CO 2  He/ CO  2  Mo  MFC  SV1 MV1  Reactor  GC  He/CO,/CO —{X  SV2  NV1  Figure 4.8: Experimental flow-diagram for the reduction o f C 0  4.4.4  2  Experimental procedure  Preliminary experiments, described i n section 4.2, gave less than 10% conversion of [ C ] c a r b o n n  dioxide to [ C ] c a r b o n monoxide, most probably due to the presence o f oxygen w h i c h oxn  idized the molybdenum to m o l y b d e n u m trioxide. A s p e n e q u i l i b r i u m data suggests that the temperature at w h i c h m o l y b d e n u m oxides are reduced to m o l y b d e n u m metal depends on the molar ratio o f hydrogen to molybdenum. F o r a ratio o f H : M o o f 240, complete reduction to m o l y b d e n u m occurs at 4 0 0 ° C . F o r a ratio o f 2  F f : M o o f 7.5, complete reduction to m o l y b d e n u m occurs at 9 0 0 ° C . In the reactor used, 2.3 2  g o f m o l y b d e n u m wire was placed i n a length o f 10 cm within the 6.3 mm inner diameter quartz reactor. A s s u m i n g only the exposed surface atoms are available for reaction, this corresponds to a molar ratio for H : M o o f 130. A t this molar ratio, A s p e n generated data 2  indicates that 4 2 5 ° C w o u l d be sufficient for reduction to molybdenum. There is a general agreement that the reduction o f m o l y b d e n u m trioxide with hydrogen to molybdenum metal is a two step process, forming m o l y b d e n u m dioxide as intermediate, though the exact temperature at w h i c h reduction is reported varies. The reduction o f m o l y b denum trioxide to m o l y b d e n u m dioxide is reported to occur between 350-600°C w h i l e the reduction o f m o l y b d e n u m dioxide to molybdenum is reported to occur between 5001 1 5 0 ° C . L e e et al. [54] prepared molybdenum by T P R o f 0.5 g M o 0  3  powder with pure  hydrogen at 50 c m / m i n , from 3 0 0 ° C to 7 0 0 ° C , increasing temperature 60 ° C / h . 3  57  Carbon monoxide is more strongly adsorbed on freshly reduced m o l y b d e n u m carbide than unreduced m o l y b d e n u m carbide [54]. Iwasawa et al. [55] observed deposition o f small amounts o f carbon on m o l y b d e n u m fixed on alumina, after it had been reduced w i t h hydrogen at 5 0 0 ° C  for 5 h .  A l t h o u g h no data was provided for adsorption o f carbon  monoxide and carbon dioxide on freshly reduced molybdenum, there is a chance that adsorption is higher on freshly reduced m o l y b d e n u m as w e l l . L e e et al. [54] suggested to passivate d i m o l y b d e n u m carbide w i t h 1 % o x y g e n at room temperature prior to removal o f carbide from the reactor for surface analysis. F o l l o w i n g L e e ' s [54] procedure, temperature programmed reduction was performed on the m o l y b d e n u m wire, from 300 to 7 0 0 ° C w i t h a temperature increase o f 6 0 ° C / h , w i t h an additional 12 hours of isothermal reduction at 7 0 0 ° C . U H P hydrogen, w h i c h contained 50 p p m o f C O and 50 p p m CO2 was used as reduction media. F o l l o w i n g c o o l i n g , the m o l y b d e n u m wire was passivated w i t h U H P compressed air, at r o o m temperature, for one hour. Experiments were carried out using the experimental set-up illustrated i n figure 4.8. The experiments were separated in two parts, temperature programed reaction and flowrate programed reaction. For the temperature programed reaction experiments, the gas stream was fed through the reactor at a fixed pressure o f 2  bar and a fixed flowrate o f 4 cm /min ( S T P ) . T h e 3  temperature o f the m o l y b d e n u m wire was varied from 331 and 8 8 3 ° C , i n increments o f approximately 6 0 ° C . A t each temperature, 2 cm samples o f the gas product were analyzed 3  using G C for quantification o f carbon dioxide and carbon monoxide. F o r the flowrate programmed experiments, the m o l y b d e n u m wire was kept at a fixed temperature o f 8 2 5 ° C and the feed gas was kept at constant pressure o f 2 bar. flowrate o f the feed stream containing 50 p p m C 0  2  The  in h e l i u m was varied from 5 to 1642  cm /min ( S T P ) . A t each flowrate, a 2 cm sample o f the gas product was analyzed using 3  3  G C for quantification of carbon dioxide and carbon monoxide.  58  4.4.5  Results and discussion  D u r i n g the reduction of m o l y b d e n u m , water vapor was visible at the outlet o f the reactor, indicating that m o l y b d e n u m oxides were present initially. A t the end o f the isothermal reduction at 7 0 0 ° C , water vapor was no longer visible. There was some concern that m o l y b denum carbide may have been formed, due to the presence o f 50 p p m carbon m o n o x i d e and carbon d i o x i d e i n the hydrogen gas. G C analysis of the product stream showed a single peak, methane, indicating that carbon oxides reacted w i t h hydrogen to f o r m methane. A d d i t i o n a l A s p e n e q u i l i b r i u m simulations indicated that the only components i n the product stream at e q u i l i b r i u m at 7 0 0 ° C are molybdenum, methane, water and hydrogen. T h e m o l y b d e n u m wire had a shiny metallic finish, characteristic o f m o l y b d e n u m metal. It was concluded that m o l y b d e n u m oxides were present and that they were reduced to molybdenum. The effect o f temperature on the ratio o f C O to total carbon oxides i n the product stream from a feed stream containing 50 p p m C 0  2  reacting w i t h m o l y b d e n u m from 331  and 8 8 3 ° C is illustrated i n figure 4.9. Three distinct stages can be observed:  1. from 331 to 6 0 0 ° C , a plateau w i t h average C O / ( C 0 + C O ) o f 2 0 % , 2  2. from 600 to 7 0 0 ° C , an abrupt increase from 2 0 % to over 7 0 % C O / ( C 0 + C O ) 2  3. from 700 to 8 8 3 ° C , a plateau w i t h average C O / ( C 0 + C O ) o f 71 % . 2  A similar abrupt increase i n carbon monoxide generation was observed by Zeisler et al. [40] at 8 2 5 ° C (see figure 2.3), for reaction o f C 0 n  2  w i t h m o l y b d e n u m , and by S o l y m o s i et  al. [66] at 6 0 0 ° C (see figure 2.4), for reaction o f carbon dioxide w i t h m o l y b d e n u m carbide. A s p e n generated e q u i l i b r i u m data shows an abrupt increase i n the conversion o f C 0  2  to C O , as illustrated i n figure 4.7. T h e most notable difference between A s p e n generated equilibrium data and experimental data is the fact that A s p e n data suggests the absence o f carbon oxides i n the lower temperature plateau. However, experimental data from this study  59  80% -| *  70% -  x  X  X  x  60% -  6  o+ o o o o  50% 40% -  X  X  30% 20% -  X  X  X.  K  10% 0% 500  600  700  800  1000  900  T(K)  1100  Figure 4.9: Effect o f temperature on reaction o f C 0  2  1200  1300  and M o , at 4  cm /min and 2 bar 3  and others indicate that carbon monoxide is present at the lower temperature plateau. A s p e n equilibrium data suggests that i n the lower temperature plateau all the carbon dioxide reacts w i t h m o l y b d e n u m to form d i m o l y b d e n u m carbide and m o l y b d e n u m dioxide, as illustrated in figure 4.5. However, experimental results show that both carbon dioxide and carbon monoxide are present between 331 to 6 0 0 ° C . O v e r a l l , A s p e n appears to be a good tool to determine the general profile for e q u i l i b r i u m conversions o f carbon dioxide to carbon monoxide as a function o f temperature for the conditions o f this study, i n particular for the second and third temperature stages described above. The effect o f flowrate on the ratio o f C O to total carbon oxides i n the product stream from a feed stream containing 50 p p m C O  reacting with m o l y b d e n u m at 8 2 5 ° C is illus-  2  trated i n figure 4.10. Between 5 and 70 c m / m i n ( S T P ) , there is no significant change in 3  the ratio o f carbon monoxide to total carbon oxides, averaging 7 6 % . A t 70 c m / m i n ( S T P ) , 3  the ratio o f carbon monoxide to total carbon oxides decreases exponentially from 7 4 % to less then 2 % at approximately 1250 c m / m i n ( S T P ) . 3  The total amount o f carbon oxides i n the product stream exceeded the 51.4 p p m carbon  60  250  500  1,000  750  1,250  1,500  1,750  Flowrate (seem) Figure 4.10: Effect o f flowrate on reaction o f C 0 and M o at 8 2 5 ° C and 2 bar 2  dioxide contained i n the feed stream. F o r this reason, both figure 4.9 and 4.10 were plotted as a ratio o f carbon monoxide to total carbon oxides. Figures 4.11 and 4.12 show the total amount o f carbon oxides i n the product stream, as a function o f temperature and flowrate respectively. In figure 4.11, the data follows a similar trend as the curve in figure 4.9. There is an initial increase i n total carbon oxides i n the product stream from 50 p p m to around 120 p p m , from 340 to 4 0 0 ° C . Between 400 and 6 0 0 ° C , the amount o f carbon oxides gradually decreases from 120 p p m to 90 p p m .  Between 600 and 8 0 0 ° C , there is a m u c h larger  increase from 90 to 450 p p m carbon oxides. F r o m 800 to 8 8 0 ° C , the amount remained constant at 450 p p m . In figure 4.12, the total amount o f carbon oxides decreases exponentially from 75 p p m down to around 50 p p m . Considering that the flow experiment were done after the temperature experiments, this decrease from 75 to 50 p p m appears to be the tail end o f the larger peak seen in figure 4.11, beginning at 6 0 0 ° C . There are two possible explanations for the source o f this additional carbon. T h e first possibility is that m o l y b d e n u m carbide may have formed at the lower temperature during 61  100  90 80  10  250  500  750  1,000  1,250  1,500  1,750  Flowrate (seem) Figure 4.12: Total carbon oxides as a function o f flowrate.  62  start-up of the apparatus and reacted w i t h carbon dioxide and/of molybdenum dioxide to form carbon monoxide. The second possibility is that carbon dioxide and/or carbon monoxide remained adsorbed on the molybdenum surface prior to experiments and were released during experiments. A s p e n generated e q u i l i b r i u m data suggests that M o C and M o 0 2  2  are formed by react-  ing molybdenum w i t h carbon dioxide, from r o o m temperature to 5 0 0 ° C. However, published data on formation o f m o l y b d e n u m carbide from carbon monoxide w i t h m o l y b d e n u m dioxide, according to the reversible eq. 2.14 on page 26, proceeds at temperatures above 565°C [57]. The formation o f m o l y b d e n u m carbide by reaction o f C H  4  i n hydrogen w i t h  molybdenum trioxide was reported to occur above 500°C. Thus, regardless of how m o l y b denum carbide is formed, it appears that the temperature must be over 500°C and that the carbon source must react w i t h a m o l y b d e n u m oxide. In Figure 4.11, there is always more than 51.4 ppm total carbon i n the product stream, indicating that carbon dioxide probably did not react w i t h molybdenum to form molybdenum carbide. Thus, the possibility that molybdenum carbide was the source o f additional carbon seems highly improbable. Considering the second possibility, numerous studies have found C O and carbon adsorption on molybdenum compounds is significant, in particular after reduction w i t h hydrogen [54, 55]. D u r i n g preparation o f the molybdenum, after T P R reduction, some carbon dioxide and carbon monoxide may have remained adsorbed on the freshly reduced m o l y b denum w h i l e c o o l i n g to r o o m temperature. D u r i n g start-up o f the experiments, helium containing 51.4 p p m carbon dioxide was flowing through the reactor. Since up to 120 p p m carbon dioxide was measured i n the product stream, it is highly probable that some carbon dioxide was previously adsorbed on the molybdenum surface. The adsorption of carbon monoxide and carbon dioxide on the molybdenum surface during start-up and pretreatment seems to be the most l i k e l y source o f additional carbon measured during experiments. The components molybdenum, molybdenum oxides, m o l y b d e n u m carbides and carbon oxides constitute a complex system. T h e equilibrium data generated by A s p e n provided  63  a good prediction o f the achievable y i e l d o f carbon monoxide. F o r the high temperature plateau, the reduction o f C 0 to C O proceeds according to eq. 4.6, o x i d i z i n g m o l y b d e n u m 2  to m o l y b d e n u m dioxide.  64  Chapter 5 Experimental: Methanol synthesis 5.1  Introduction  In order to estimate the requirements for the production o f [ C ] m e t h a n o l v i a a gas phase n  catalytic process, a series o f experiments have been conducted w i t h non-radioactive carbon monoxide. A l t h o u g h c o m m e r c i a l methanol production involves a catalytic gas phase process, no practical procedure is currently available for the production o f [ C ] m e t h a n o l . The n  industrial production o f methanol uses catalysts such as C u / Z n O / A l 0 2  3  that are prepared  by co-precipitation and activated w i t h 1-3% hydrogen at 2 5 0 - 2 9 0 ° C prior to use. T h e feed gas is normally syngas, w h i c h contains C O , C 0 , C H and H , w i t h the carbon dioxide 2  4  2  acting as an o x i d i z i n g agent. This study aimed at determining the suitability o f the catalytic gas phase procedure for the production o f [ C ] m e t h a n o l . A c t i v a t i o n and precondition of a copper zinc oxide n  catalyst were evaluated. T h e effect o f pressure, temperature and flowrate o f the feed gas on the methanol y i e l d were studied and a kinetic m o d e l was generated. T h e model was used to establish optimal condition and estimate the potential yields o f [ C ] m e t h a n o l production 11  v i a a catalytic gas phase method.  65  5.2 Materials and methods In order to be consistent with conditions encountered during carbon-11 labelling procedures, a 50 ppm CO feed gas was selected (see page 105). It consisted of certified 50 ppm CO in hydrogen, which was supplied in a 100 bar standard laboratory size gas cylinder. UHP helium gas, contained in a 100 bar standard laboratory cylinder, was used as inert sweep gas. The gas flow rate was controlled by a mass flow controller (MKS instruments) for flow rates below 70 cm /min and by an adjustable needle valve correlated flowmeter (Cole3  Parmer) for higher flowrates. Calibration of both flow control devices was done using the soap-bubble method, for which calibration curves are included in the appendices, on page 91. A manual 3-port valve (Swagelok) was placed at the inlet of the reactor, to select either helium or the feed gas. The reactor consisted of a 400 W ceramic tubular heater (Omega Heating) in which a 6.3 mm inner diameter stainless steel tube was placed, which contained the copper based catalyst, covering a length of 6 cm. A K-type thermocouple was placed in the middle of the ceramic heater, and a second K-type thermocouple was placed inside the reactor, in contact with the catalyst. The reactor temperature was controlled with a manual operated thermostat (Omega). Quartz tubes, 6.3 mm outer diameter with 1 mm inner diameter, where placed on both ends of the reactor to reduce the void space and the time required for the product gas to flow through the remaining portion of the reactor. Glass wool plugs were placed on both ends of the heater, to improve temperature uniformity. The resulting temperature profile of the reactor is included in the appendices. The outlet of the reactor was connected to a pressure regulator to maintain downstream pressure below the rating of the flow control devices. The product stream was also connected to a 6-port sampling valve (VICI). The 6-port valve was connected to a waste stream, a 2 cm sample 3  loop, a hydrogen supply and the inlet of a varian 3600 gas chromatograph, equipped with a flame ionization flame detector (FID). The GC was equipped with a 3 m long stainless 66  steel c o l u m n (1.6 mm  inner diameter) packed with 60-80 mesh poropak. U s i n g a stream  of helium saturated with methanol, a calibration curve was generated and is illustrated i n the appendices, on page 93.  5.2.1  Cu/ZnO catalyst preparation  C o p p e r nitrate pentahemihydrate, C u ( N 0 ) • 2 . 5 H 0 , and sodium carbonate were obtained 3  2  2  from A l d r i c h . Z i n c nitrate hexahydrate, Z n ( N 0 ) • 6 H 0 was obtained from J T Baker. 3  2  2  The procedure used for the preparation of the copper zinc oxide catalyst was based on the method described by H e r m a n et a l . [71]. A 1.0 M solution o f copper nitrate was prepared by dissolving 21.6 g copper nitrate pentahemihydrate i n 92.9 mL distilled water. Similarly, a 1.0 M zinc nitrate solution was prepared by dissolving 64.5 g i n 216.7 m l distilled water. These nitrate solutions were m i x e d to obtain a 30:70 molar ratio o f C u : Z n . A 1.0 M solution o f sodium carbonate was prepared by dissolving 50 g N a C 0 2  3  i n 472  mL distilled water and was added dropwise to the 310 mL metal nitrates solution at 9 0 ° C , until the p H was raised from 2 to 7.0. T h e titration took 5 h and consumed approximately 360 mL sodium carbonate. F o l l o w i n g a 12 h digestion at r o o m temperature, the turquoise precipitate was filtered over glass frit and dried overnight at 8 5 - 1 0 5 ° C . T h e subsequent calcination o f the copper/zinc carbonates was carried out i n air by heating from 150 to 3 5 0 ° C i n 2 h, with the m a x i m u m temperature maintained for 4 h. T h e resulting copper/zinc oxides were pelletized from an aqueous slurry, dried at ambient temperature and crushed and screened to a uniform size o f 650 ± 200 |j.m. Samples o f 2 g were placed i n the reactor, covering a length o f 6 cm. T h e catalyst was reduced under flow o f 2 % hydrogen i n h e l i u m , for 12-16 h at 2 5 0 ° C and 1 bar. A standard B E T method was used for the determination of surface area from argon adsorption at - 1 9 6 ° C and the surface area o f the reduced, used catalyst, was 30.3 m /g. 2  This is in the same range as measurements made by H e r m a n et  al., w h o reported a surface area o f 37.1 m / g 2  for catalyst prepared by a similar method,  and used under c o m m e r c i a l methanol synthesis conditions [71].  67  5.3  Experimental procedure  T h e flow diagram for the experimental setup used for the methanol synthesis reactor is illustrated i n figure 5.1. H/CO/CHjOH  MV1  H / CO 2  -fc<r-  MeOH Reactor  ryCO/CH OH 3  -CXr  He  Figure 5.1: Experimental flow diagram for methanol synthesis  C o m m e r c i a l l o w pressure methanol synthesis is typically performed between 2 0 0 - 2 7 0 ° C and at 50 - 100 bar [78]. T h e practical pressure for [ C ] m e t h a n o l production is about 50 bar, u  due to pressure rating o f c o m m o n l y used valves, tubing and fittings i n automated synthesis units. A s p e n generated e q u i l i b r i u m data for the system containing 50 p p m C O , is illustrated i n figure 5.2, as conversion o f C O to methanol as a function o f temperature and pressure. The conversion was calculated by dividing e q u i l i b r i u m amounts o f methanol by initial amounts o f carbon monoxide. D u e to the exothermic nature o f methanol synthesis, as temperature increases, the e q u i l i b r i u m conversion o f carbon monoxide to methanol decreases. F o r a given temperature, as the pressure increases, the e q u i l i b r i u m conversion o f carbon monoxide to methanol increases. A t 50 bar, e q u i l i b r i u m conversion o f C O to methanol is 100% for temperatures below 1 8 0 ° C and decreases to 9 0 % at 2 4 0 ° C .  5.3.1 Preliminary experiments: Cu/ZnO catalyst for C H O H synthe3  sis Preliminary experiments were performed using a continuous feed containing 50 p p m C O in hydrogen at temperatures ranging from 180 to 2 4 0 ° C , flowrates ranging from 2 to 126  68  100  200 I— -2bar  300  400  Temperature (°C) -10 b a r - - -5.0 b a r -  500  250bar|  Figure 5.2: A s p e n generated equilibrium conversion o f 50 p p m C O to methanol, i n hydrogen c m / m i n ( S T P ) and pressures ranging from atmospheric to 2, 10 and 55 bar. The catalyst 3  was pretreated by reduction at 2 5 0 ° C with 2 % H i n h e l i u m for initial experiments. Subse2  quent experiments were performed using the same catalyst reduction conditions, however the catalyst was passivated by exposure to compressed air at 2 0 ° C . T h e feed gas, containing 50 p p m C O i n hydrogen, was continuously fed through the reactor and the product stream gas was sampled every 5-30 minutes and analyzed using the gas chromatograph for quantification o f methanol produced.  5.3.2 Effect offlowrateand temperature on C H O H synthesis 3  In the final application, w i t h carbon-11, the process w i l l be performed semi-batchwise. A c c o r d i n g l y , further experiments were carried out semi-batchwise. Prior to experiments, the catalyst was reduced as described previously. P r i o r to each experiment, the catalyst was o x i d i z e d by exposing it to compressed air at ambient temperature.  69  Effect offlowrateon methanol production: T h e system was pressurized w i t h h e l i u m at 55 bar, and flowmeter set to either 26, 93, 241, 468 and 935 c m / m i n ( S T P ) . T h e reactor heater was turned on and set to 1 8 0 ° C , and 3  samples o f the product stream were analyzed using the gas chromatograph to ensure that no methanol was present. T h e feed gas was then switched to 50 p p m C O i n hydrogen at 55 bar, for a period o f 10-300 minutes giving between 0.3-0.9 c m  3  ( S T P ) carbon monoxide.  U s i n g the 6-port sampling valve, samples were analyzed using the gas chromatograph to quantify methanol concentration, typically at 2-5 minute intervals. After the predetermined C O feed time had elapsed, the tubing prior to reactor was vented and loaded with h e l i u m . W h e n the reactor pressure reached 2 bar, the supply gas was switched to 2 bar h e l i u m and the flow rate was set to 126 c m / m i n ( S T P ) . T h e product stream was sampled and analyzed 3  using the gas chromatograph until methanol was no longer observed.  Effect of temperature on methanol production: T h e system was pressurized w i t h h e l i u m at 55 bar, and flowmeter set to 126 c m / m i n ( S T P ) . 3  T h e reactor heater was turned on and set to either 154, 178, 209, 224 or 2 4 0 ° C , and samples o f the product stream were analyzed using the gas chromatograph to ensure that no methanol was present. A l t h o u g h c o m m e r c i a l methanol synthesis is performed between 2 0 0 - 3 0 0 ° C , the experiments were limited to 2 4 0 ° C to avoid irreversible deactivation o f the catalyst, w h i c h is reported to occur when catalyst is operated above 2 4 5 ° C and i n the absence o f an o x i d i z i n g agent [72, 7 1 , 69]. T h e feed gas was then switched to 50 p p m C O in hydrogen at 55 bar, for a period o f 20 minutes. temperatures, and corresponds to 0.126 c m  3  The time was the same for all  ( S T P ) o f carbon monoxide. U s i n g the 6-port  sampling valve, samples were analyzed using the gas chromatograph to quantify methanol concentration, typically at 2 minute intervals. After the predetermined C O feed time had elapsed, the tubing prior to reactor was vented and loaded with h e l i u m . W h e n the reactor pressure reached 2 bar, the supply gas was switched to 2 bar h e l i u m and the flow rate was  70  set to 126 c m / m i n ( S T P ) . T h e product stream was sampled and analyzed using the gas 3  chromatograph until methanol was no longer observed.  5.4 5.4.1  Results and discussion: Preliminary experiments: Cu/ZnO catalyst  Preliminary experiments were performed using a continuous feed o f 5 0 p p m C O i n H , at 2  temperatures ranging from 180 to 2 4 0 ° C , flowrates ranging from 2 to 126 c m / m i n ( S T P ) 3  and pressures o f 2, 10 and 55 bar, using the reduced copper zinc oxide catalyst. N o methanol was measured i n the product stream under these conditions. T h e catalyst was then passivated with compressed air at 2 0 ° C , and the experiments were repeated. Experiments performed at 55 bar resulted i n measurable amounts o f methanol i n the product stream. However, experiments performed at 2 and 10 bar using the same experimental conditions failed to produce any detectable amount o f methanol i n the product stream. U s i n g the passivated catalyst and operating pressure o f 55 bar, further experiments were performed to measure the methanol produced as a function o f time, for a continuous feed o f H / C O . T h e amount o f methanol i n the product stream increases w i t h time, 2  then reaches a m a x i m u m , followed by a gradual decrease, as illustrated i n figure 5.3. T h e methanol production appears to gradually stabilize, however there is no clear indication that a steady state is reached. F o r the experiment at 1 8 0 ° C , 55 bar and 2 c m / m i n ( S T P ) , 3  the concentration o f methanol increases to a m a x i m u m o f 45 p p m after about 150 minutes and then decrease to just under 18 p p m at 400 minutes. F o r the experiment at at 2 0 0 ° C , 55 bar and 26 c m / m i n ( S T P ) , the concentration o f methanol increases to a m a x i m u m o f 12 3  p p m after about 75 minutes and then decreases to 7 p p m at 200 minutes.  T h e initial peak i n methanol production is likely due to the presence o f adsorbed carbon 71  150  200 Time(min)  250  300  350  400j  1180 °C; 55 bar, 2 cm3,'min(STP) x 200 °C, 55 bar, 26 cm3/min (STP)J  Figure 5.3: M e t h a n o l produced for continuous feed o f H / C O 2  monoxide on the catalyst. W h i l e the reactor was heated to the operating temperature, the feed gas was 50 p p m C O i n H . Thus carbon monoxide may have accumulated on the 2  c o l d catalyst surface and reacted once the temperature was sufficiently high. A d s o r b p t i o n of carbon monoxide on a copper zinc oxide catalyst at ambient temperatures has been previously described [72, 74]. K l i e r [72] reports that for a catalyst with 30/70 ratio o f C u / Z n O , 1.7 m o l of C O / g catalyst reversibly chemisorbs to the catalyst surface. In summary, the preliminary results confirm that methanol can be produced from a feed stream containing 50 p p m C O i n H using an activated and passivated C u / Z n O cata2  lyst. These experiments also indicate that an operating pressure o f 55 bar is adequate for methanol synthesis, while operating pressures below 10 bar are insufficient. T h e data suggests that carbon monoxide accumulated on the catalyst at ambient temperature and only appeared i n the product stream as methanol once the operating temperature was reached. The experimental procedure for subsequent experiments was adapted accordingly: the catalyst was passivated prior to each experiment and the reactor was allowed to reach its operating temperature under helium flow before switching to the H / C O feed gas. 2  72  20.  O-  5. c o  510 ra £  5  2,500  5,000  7500  10,000  12,500  Cumulative Volume [ c m , S T P ) J  l^e-  2 6 s e e m —— 9 3 s e e m - * - 241 s e e m - * - 4 6 8 s e e m - & - 9 3 5 s e e m |  Figure 5.4: Semi-batch methanol produced, 180°C, 50 bar for different flowrates  5.4.2  Effect offlowrateand temperature on C H O H synthesis 3  For experiments performed under semi-continuous feed of H / C O , the concentration of 2  methanol in the product stream vs. cumulative product stream volume is illustrated in figures 5.4 and 5.5.  Effect offlowrateon methanol production: Experiments were performed at 180°C, 55  bar and  flowrates were varied between 26 and 925  creases from 26 to 935  cm /m 3  cm /min 3  (STP). A s the flowrate in-  (STP), the conversion of carbon monoxide to methanol  decreases from 26% to 0.5% (Table on the next page). A s can be seen in figure 5.4, the methanol is released in two distinct peaks. The first methanol peak was released while H / C O was fed to the reactor while the second peak was released during the he2  lium purge, at 180°C, 126 to 935  cm /m 3  cm /m 3  (STP) and 2  bar.  A s the flowrate increases from 26  (STP), the percentage of methanol released during the helium purge phase  decreases from 48% to 26% (Table on the following page). The fact that the methanol produced is released in two distinct peaks, suggests that methanol synthesis has at least 2 rate limiting steps. One of the rate limiting steps is likely  73  Table 5.1: Effect of flowrate on conversion of C O to methanol (50bar, 1 8 0 ° C ) Flowrate (STP) Methanol Yield % methanol released during purge 26 c m / m i n  26%  48%  93 c m / m i n  21%  35%  3  3  240 c m / m i n  10%  38%  468 c m / m i n  8%  29%  935 c m / m i n  0.5%  26%  3  3  3  Table 5.2: Effect of temperature on conversion of C O to methanol at 55bar, 126 cm /min(STP) Temperature Methanol Yield 3  8%  154°C 178°C  14%  209°C  23%  224°C  25%  240°C  48%  associated with the rate of formation of methanol. The second methanol peak occurs when the flow is switched to helium and the pressure is dropped from 55 bar to 2 bar, indicating that methanol is more readily released at atmospheric pressure than at 55 bar. Moreover, the fact that the percentage of methanol released during the purging was higher at low flowrate, suggests that methanol desorption is a second rate limiting step, which is in agreement with earlier studies of the kinetics of low-temperature methanol synthesis [79].  Effect of temperature on methanol production: cm /min 3  240°C.  Experiments were performed at 126  (STP), 55 bar and the temperature of the reactor was varied between 154 and  As the temperature increases from 154 to 2 4 0 ° C , the conversion of carbon monox-  ide to methanol increases from 8% to 4 8 % (5.2). As can be seen in figure 5.5, most of the methanol produced is released in one major peak which occured during the helium purge. Although at 2 4 0 ° C the methanol yield is the highest, a much larger volume of helium purge gas was required to release the methanol produced. At first glance, it appears that methanol is released from the catalyst as a single peak for operating temperatures between 1 5 4 - 2 2 0 ° C . This suggests that methanol synthesis has one  74  14  i  12  -.  10  -  1  2,000  4,000  6,000  8,000  10,000  12,000  14,000  16,000  Cumulative V o l u m e ( c m , S T P ) 3  |-o-154"C  178 " C  -»-209°C  - * - 224 °C - a -  24o"°c]  Figure 5.5: Semi-batch methanol produced, 120 c m / m i n , 50 bar for different tempera3  tures rate l i m i t i n g step. However, upon closer examination, three o f the profiles reveal a small satellite peak appearing just before the major methanol peak. T h e amount o f H / C O gas 2  fed to the reactor i n the temperature experiments was 2500 c m  3  ( S T P ) , w h i l e up to twice  as much was used in the flow experiments. In the latter experiments (figure (5.4)), the first methanol peak is released at about 2500 c m ( S T P ) , and the second peak is released during 3  the h e l i u m purge at over 5000 c m ( S T P ) . D u r i n g the temperature experiments, the major 3  peak was observed w h i l e the reactor was purged with helium, at a cumulative volume o f approximately 2000 c m ( S T P ) . A c c o r d i n g l y , the two peaks observed i n the flow experiments 3  w o u l d overlap i n the temperature experiments. Thus, even though there are l i k e l y two or more rate l i m i t i n g steps, only one peak appears i n the temperature experiments. A t 2 4 0 ° C , the methanol is released i n a similar initial peak, but significant trailing suggests that an additional rate l i m i t i n g step occurs. T h i s is consistent w i t h studies reporting that intra-particle diffusion limits the rate o f methanol synthesis at temperature above 2 4 5 ° C [79, 80].  75  Table 5.3: Kinetic parameters for Leonov's model For 154-240 °C, 55 bar and 26-935 cm /min(STP) Value units ko 1.3E-4 mol/(cm sbar ) kJ/mol 73 E„ 3  3  5.4.3  084  Kinetic Model  Leonov's proposed kinetic expression for methanol synthesis, illustrated in eq. 5.1, was used as a base kinetic expression to model the semi continuous CO/H feed experimental 2  results for temperature and flow experiments, given in tables 5.1 and 5.2. The values of k and Ea, for which the error between model and experimental semi-continuous results was minimized, are represented in table 5.3.  /p0.5  p  p0.34  I P0.66 V CH OH r  r  3  k  =  k  o -  e  p0.5 . p C O H  \  r  * p ( - p ^ )  2  .TS I ^eq/ (5-2)  Figure 5.6 illustrates the conversion of 50 ppm carbon monoxide in hydrogen to methanol, as a function of temperature, at 55 bar and 126 cm /min (STP), for the semi-continuous 3  experimental results, for the kinetic model generated using Hysys, and for equilibrium data generated using Hysys. As the temperature increases from 100 to 175°C, the equilibrium conversion of carbon monoxide to methanol remains at 100%, after which it decreases to 44% as the temperature increases further to 300°C. As the temperature increases from 154 to 240° C, the experimental conversion of carbon monoxide to methanol increases exponentially from 8% to 48%. As the temperature increases from 100 to 270°C, the conversion of carbon monoxide computed from the kinetic model increases exponentially from 2% to a maximum of 55%. As the temperature increases beyond 270° C, the conversion of carbon monoxide computed from the kinetic model decreases following a similar trend as  76  240  260  280  300  Reactor temperature (°C) f X  Experimental Data  Equilibrium Data •  Kinetic Model  Kinetic Model (26 seem) |  Flowrate 126 cm /min (STP) and pressure 55 bar 3  Figure 5.6: Conversion of carbon monoxide to methanol vs. temperature the equilibrium data, with an offset of approximately 6%, to reach a conversion of carbon monoxide to methanol of 38% at 300°C. The average difference between the experimental conversion of carbon monoxide to methanol and the value computed from the kinetic model is 3.6%. Figure 5.7 illustrates the conversion of 50 ppm carbon monoxide in hydrogen as a function of feed flowrate, at 180°C and 55 bar for the semi-continuous experimental data and for the kinetic model generated using Ffysys. As the flowrate increases from 26 to 935 cm /min (STP), the experimental conversion of carbon monoxide to methanol decreases 3  exponentially from 28% down to less than 1%. As the flowrate increases from 3 to 935 cm /min (STP), the conversion of carbon monoxide computed from the kinetic model 3  decreases exponentially from 100% to 4%, while forflowratesbelow 3 cm /mm (STP) the 3  conversion of carbon monoxide is 100%. The average difference between the experimental conversion of carbon monoxide to methanol and the value computed from the kinetic model is 3.3%. Applying these results to the use of carbon-11 for the synthesis of [ C]methanol ren  77  2 0 0  4 0 0  6 0 0  8 0 0  1 0 0 0  Gas Flowrate (cm /mln, STP) 3  j X Experimental Data  Kinetic Model I  Temperature 180°C and pressure 55 bar Figure 5.7: Conversion of carbon monoxide to methanol vs. flowrate quires many considerations. Firstly, the short half life of carbon-11 limits the time allocated to methanol synthesis to less than 5 minutes. Secondly, the [ C]CO would be delivered in 11  approximately 100 c m (STP) in hydrogen, which is an order of magnitude less than what 3  was used in the semi-continuous experiments. As illustrated in figure 5.5, the cumulative volume required to release most of the methanol produced is less than 5000 c m (STP), 3  which is twice as much as the feed gas volume. Assuming the same correlation applies for the release of [ C]methanol, this would translate to an elution volume of less than 400 n  c m (STP). Together with the 5 minutes time allocated for methanol synthesis, the mini3  mumflowratewould thus be 20 c m / m i n (STP). The highest conversion of carbon monox3  ide to methanol computed from the kinetic model occurs at a temperature at approximately 270°C  (figure 5.6). At temperatures above 2 4 5 ° C intra particle diffusion limitations have  been observed [80, 79]. Moreover, as illustrated in figure 5.5, at high temperatures the amount of sweep gas required to elute the methanol produced is significantly higher than at temperatures below 2 2 4 ° C . This suggests that the optimal temperature for the carbon-11 application should be around 2 2 4 ° C . At 2 0 c m / m i n (STP), 2 2 4 ° C and 55 bar, the kinetic 3  78  model predicts a conversion of carbon monoxide to methanol of over 60%.  79  Chapter 6 Conclusion and Recommendations  6.1 Conclusions C a r b o n molecular sieves, in particular when cooled to - 2 0 ° C , quantitatively trap and release carbon dioxide upon heating to 1 0 0 ° C . A trap has been developed w h i c h quantitatively retains and releases C 0 n  2  i n less than 3.5 minutes. T h o u g h many existing traps are capable  of quantitative trapping, the net advantage o f this design lies i n its compact size, rapid heating and c o o l i n g times, and use o f T E C ' s as opposed to l i q u i d nitrogen. T h i s enables repeated use o f the apparatus, without addition o f l i q u i d nitrogen. A u t o m a t i o n o f the system w o u l d allow delivery o f a semi-continuous supply o f C 0 n  2  for downstream processing, at  less than 10 minute intervals. Carbon dioxide reacts w i t h m o l y b d e n u m to form m o l y b d e n u m dioxide and carbon monoxide. Trace amounts of carbon oxides remain adsorbed on reduced m o l y b d e n u m , and desorb at 8 0 0 ° C , in e q u i l i b r i u m ratios. Reduced, then passivated m o l y b d e n u m is suitable for reduction o f 50 p p m carbon dioxide i n h e l i u m , to y i e l d carbon monoxide at 8 0 0 - 8 8 0 ° C , 2 bar and flow rates under 70 c m / m i n ( S T P ) . Conversions i n the order of 7 0 % are pos3  sible at these conditions. A s p e n , a c o m m e r c i a l l y available process simulator, was used to predict the e q u i l i b r i u m conversion o f trace amounts o f carbon dioxide to carbon monox-  80  ide, by reaction w i t h m o l y b d e n u m . Conversions predicted w i t h this process simulator were consistent w i t h the experimental results. Trace amounts o f carbon monoxide react w i t h hydrogen to form methanol, on a copper zinc oxide catalyst. Reduced, then passivated copper zinc oxide is suitable to catalyze the reaction o f 50 p p m carbon monoxide w i t h hydrogen, to form methanol at 1 8 0 - 2 4 0 ° C , 55 bar and 2-935 cm /min ( S T P ) . B a s e d on experimental data, a kinetic m o d e l was created 3  using a c o m m e r c i a l l y available process simulator, H y s y s . T h e kinetic model was used to predict optimal operating conditions for practical quantities o f [ C ] m e t h a n o l , i.e. n  6 0 % conversion of [ C ] c a r b o n monoxide, at 2 2 4 ° C , 55 u  6.2  over  bar and 20 cm /min ( S T P ) . 3  Recommendations for future work  T h e proposed  n  C 0  trap can be incorporated into any process requiring C 0 2 . However, U  2  experiments for C O production suggested that the removal o f oxygen from the trap was u  insufficient, using a 30 s h e l i u m flush at 200 cm  3  ( S T P ) w h i l e the trap was at - 2 0 ° C . It  is recommended to flush the trap w i t h h e l i u m during the heating step or adding a step i n w h i c h h e l i u m flows through the trap at r o o m temperature to ensure that a l l the o x y g e n is removed. T h i s w i l l enable a supply o f o x y g e n free  n  C 0 2 to the downstream process,  avoiding potential contamination w i t h oxygen. W h e n implementing this trap i n a process, final adjustments should be done to the h e l i u m purge step to ensure that all the o x y g e n from the target gas is removed. The proposed m o l y b d e n u m reactor to convert C 0  2  to C O can be readily incorporated  in a process requiring C O . T h e experimental results suggest that carbon m o n o x i d e and/or n  carbon dioxide remain adsorbed on the m o l y b d e n u m surface at ambient temperatures and desorb at about 8 0 0 ° C . A c c o r d i n g l y , care must be taken to remove any traces o f 1 2  1 2  C0  2  or  C O from the m o l y b d e n u m prior to use for C O production, to ensure that this step does n  not reduce the overall specific activity o f the final product. T h i s may be accomplished by  81  flushing the reactor with U H P helium prior to use, w i t h the reactor heated slightly above operating temperature.  T h e reactor should also remain under inert gas w h i l e not used,  preferably slightly under pressure, to avoid contamination w i t h carbon-12. Experiments performed w i t h 50 p p m C 0  indicate that conversions o f C 0 n  2  2  to  1 1  C O i n the order o f  7 0 % are attainable. The proposed methanol reactor w o u l d be suitable to incorporate in a process requiring u  C H O H , such as the production o f C H I with high specific activity. T h e experimenn  3  3  tal results suggest that carbon m o n o x i d e and/or carbon dioxide remained adsorbed on the copper-zinc oxide surface at ambient temperatures and desorb at about 2 0 0 ° C . ingly, care must be taken to remove any traces o f  1 2  C0  2  or  1 2  Accord-  C O prior to catalyst use, to  ensure that the final product specific activity remains high. This may be accomplished by flushing  the reactor w i t h U H P h e l i u m prior to use, w i t h the reactor heated slightly above  operating temperature.  T h e reactor should also remain under inert gas w h i l e not used,  preferably slightly under pressure, to avoid contamination with carbon-12. B a s e d on experimental results obtained using 50 p p m C O and the kinetic model, conversion o f C O n  n  to C H O H i n the order of 6 0 % are expected. n  3  C o m b i n i n g the  n  C0  2  trap, m o l y b d e n u m reactor and the gas phase methanol reactor,  the entire process has the potential to produce C H O H i n c l i n i c a l l y usable quantities. The u  3  advantage of the proposed gas phase synthesis over the conventional l i q u i d phase method is the potential to obtain high specific activity carbon-11 radiopharmaceuticals. Further studies w i t h carbon-11 should be done to confirm these projections and to adapt this system to existing P E T facilities.  82  Bibliography [1] J . Zessin and P. M a d i n g .  Automated  Production  o f [1 l C ] M e t h y l  Iodide.  Forschungszent. Rossendorf, F Z R : 2 7 0 , 1999. [2] P . H . Elsinga.  Radiopharmaceutical Chemistry for Positron E m i s s i o n Tomography.  Methods, 2 7 : 2 0 8 - 2 1 7 , 2002. [3] Y . 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H a n c o c k , and B . J . Crewdson.  Catalytic process.  US patent,  5,859,070, 1999. [45] C . C r o u z e l and D . Fournier. N . C . A . gas phase production o f [1 I C ] methanol from [11C] methane: application to the online synthesis o f 1 1 C H 3 I . Sixth Targets and Chemistry Workshop, Vancouver, pages 3 1 4 - 3 1 5 , 1995.  [46] F. Oberdorfer, M . H a n i s c h , F. Helus, and W . M a i e r - B o r s t . A N e w Procedure for the Preparation o f 1 l C - L a b e l l e d M e t h y l Iodide. Int. J. Appl. radiat. hot., 1985.  87  36(6):435^138,  [47] M . Holschbach and M . Schuller. A N e w and S i m p l e O n - l i n e M e t h o d for the Preparation o f n.c.a. [ H C ] M e t h y l Iodide.  Appl. Radiat. hot., 44(4):779-780, 1993.  [48] R . F . Sebenik, R . R . Dorfler, J . M . Laferty, and G . Leichtfried.  Molybdenum and Molyb-  denum Compounds. U l l m a n n ' s E n c y c l o p e d i a o f Industrial Chemistry, 2002. [49] E d w a r d I. Stiefel.  Molybdenum Compounds. K i r k - O t h m e r E n c y c l o p e d i a o f C h e m i c a l  Technology, 2001. [50] A l f a Aesar. Material safety data sheet, m o l y b d e n u m (iv) oxide, cas 18868-43-4. Technical report, Health, Safety and Environmental Department, 2005. [51] L . V . Belyaevskaya, I.V. N a r a m o s v k i i , and N . M Girdasova. Study o f the Kinetics o f the Reduction o f Sublimated M o l y b d e n u m T r i o x i d e .  Sbornik - Moskovskti Institu  Stali i Splavov, 117:80-85, 1979. [52] P . L . G a i . Phil. Mag., A 4 3 : 8 4 1 , 1981. [53] T. Ressler, R . E . Jentoft, J . W i e n o l d , M . M . Gunter, and O . T i m p e . In Stiu X A S and X R D Studies on the Formation o f M o Suboxides during Reduction o f M o 0 3 . J. Phys.  Chem. B, 104:6360-6370, 2000. [54] J.S. L e e , S.T. O y a m a , and M . Boudart. M o l y b d e n u m carbide catalysts: Synthesis of unsupported powders.  Journal of Catalysis, 106:125-133, 1987.  [55] Y . Iwasawa and S. Ogaswara. Spectroscopic Study on the Surface Structure and E n v i ronment o f F i x e d M o Catalysts Prepareded by U s e o f M o ( C 3 H 5 ) 4 . pages 1465-1476, 1978.  [56] R . J . B u r c h .  J. Chem. Soc., Faraday Trans. 1, 74:2982, 1978.  [57] H . M . Spencer and J . L . Justice. The Reaction o f C a b o n M o n o x i d e on M o l y b d e n u m  Oxides. J. Am. Chem. Soc, 56:2301-2306, 1934.  88  [58] E . Rudy.  Compendium of Phase Diagram Data.  A i r Force Materials Laboratory,  Wright-Patterson A i r Force Base, O H . , 1969. [59] A l f a Aesar. M a t e r i a l safety data sheet, molybdenum carbide cas 12069-89-5. Technical report, Health, Safety and Environmental Department, 2005. [60] S. D i e r k s . M a t e r i a l data safety sheet, molybdenum carbide. Technical report, E S P I , 1990. [61 ] A . Vandenberghe. E i n w i r k u n g einiger Gase auf erhitztes M o l y b d a n . Z. Anorg. Chem., 11:397, 1896. [62] S. Hilpert and M . Ornstein. Ben, 46:1669, 1913. [63] E . F . S m i t h and V . Oberholtzer. J. Am. Chem. Soc., 15:206, 1893. [64] L . L i a n , S . A . M i t c h e l l , and D . M . Rayner. F l o w tube kinetic study o f m o and m o 2 reactivity. J. Phys. Chem., 98:11637-11647, 1994. [65] H . Tulhoff, H . C . Starck B e r l i n , and W . Goslar. Carbides. U l l m a n n ' s E n c y c l o p e d i a of Industrial Chemistry, 2002. [66] F. S o l y m o s i , A . O s z k o , T. Bansagi, and P. Tolmacsov. A d s o r p t i o n and Reaction o f C 0 2 on M o 2 C Catalyst. J. Phys. Chem. B, 106:9613-9618, 2002. [67] J . C . J . Bart and R . P . A . Sneeden. Copper-zinc oxide-alumina methanol catalysts revisited. Catalysis Today, 2:1-124, 1987. [68] E . Fiedler, G . Grossmann, D . B . Kersebohm, G . Weiss, and C . Witte.  Methanol.  U l l m a n n ' s E n c y c l o p e d i a o f Industrial Chemistry, 2002. [69] G . C . C h i n c h e n , P.J. Denny, J.R. Jennings, M . S . Spencer, and K . C . Waugh. Synthesis of methanol: Part 1. catalysts and kinetics. Applied Catalysis, 36:1-65, 1988.  89  [70] K . K l i e r , V . Chatikavanij, R . G . H e r m a n , and G . W . S i m m o n s .  Catalytic synthesis  of methanol from C O / H 2 : I V . T h e effects o f carbon dioxide. Journal of Catalysis, 74(343-360), 1982. [71] R . G . H e r m a n , K . K l i e r , G . W . S i m m o n s , B . P . F i n n , J . B . B u l k o , and T P . K o b y l i n s k i . Catalytic syntesis o f methanol from co/h2. i . phase composition, electronic properties, and activities o f the cu/zno/m2o3 catalyts. Journal of Catalysis, 5 6 : 4 0 7 ^ - 2 9 , 1979. [72] K . K l i e r . M e t h a n o l Synthesis. Advances in Catalysis, 3 1 : 2 4 3 - 3 1 3 , 1982. [73] P . J . A . T i j m , F . J . Waller, and D . M B r o w n . M e t h a n o l technology developments for the new m i l l e n n i u m . Applied catalysis A, pages 2 7 5 - 2 8 2 , 2 0 0 1 . [74] K . C . W a u g h . M e t h a n o l synthesis. Catalysis Today, 15:51-75, 1992. [75] S. Zeisler. Personel C o m m u n i c a t i o n s . 2003. [76] A s p e n technologies, aspen process simulator 12.5. [77] Hyprotech. H y s y s process simulator. [78] E n g l i s h A . , J . Rovner, J . B r o w n , and S. Davies. Kirk-Othmer Encyclopedia of Chemical Technology: Methanol. John W i l e y & Sons, 2005. [79] V E . Leonov, M . Karabaev, E . N . T s y b i n a , and G . S . Petrishcheva. Study o f the kintics of the methanol synthesis on a low-temeprature catalyst.  Kinet. & Ratal,  14(848-  852), 1973. [80] G . H . Graaf, H . Scholtens, E . J . Stamhuis, and A . A . C M . Beenackers.  Intra-particle  diffusion limitations in l o w pressure methanol synthesis. Chemical Engineering Science, 4 5 , 4 : 7 7 3 - 7 8 3 , 1990.  [81] Thermochemical properties of inorganic substances. Springer-Verlag, B e r l i n , 1973.  90  Appendix I: Flowmeter calibration curves T h e c o m m e r c i a l l y available M K S mass flow controller was calibrated. T h e mass control valve input voltage was varied from 0-5V, and the output flow o f h e l i u m was measured using soap-bubble technique. T h e flowrates were normalized to S T P using ideal gas law. T h e resulting calibration curve is illustrated i n figure 6.1, for w h i c h a linear trendline was added. The equation relating input voltage signal to actual flow is shown in eq. 6.1, for w h i c h the R-squared value was 0.9996 indicating a good correlation. The 65 mm correlated ball flowmeter, obtained from Cole-Parmer, was calibrated i n a similar fashion. T h e needle valve was adjusted so the reading was 10, 20, 30, 40, 50 and 60. A t each point, the flow was measured using soap bubble technique, and adjusted to S T P using ideal gas law. T h e resulting calibration curve is illustrated i n figure 6.2, for w h i c h a linear trendline was added. T h e equation relating scale reading to actual flow is shown i n eq. 6.2, for w h i c h the R-square value was 0.996 indicating a good correlation.  FMFC(VJ)  =  13.45V;  (6.1)  FcFc(Vi)  = 28.89Vi  (6.2)  91  80  0  1  2  3  4  5  6  Input Voltage (V)  Figure 6.1: M a s s flow control valve calibration curve  Figure 6.2: Correlated ball flowmeter calibration curve  92  Appendix II: C 0 , CO, CH OH 2  3  calibration curves Samples o f carbon monoxide, carbon dioxide or methanol were injected i n Varian 3600 gas chromatograph equipped w i t h a flame ionization detector and a custom built methanizer. The c o l u m n used was a 3 m l o n g , 3.2 m m outer diameter, stainless steel tube packed w i t h 60-80 mesh carbon molecular sieve, obtained from A l l t e c h . A typical chromatogram is illustrated i n figure 6.3, for a sample containing 50 p p m carbon monoxide. T h e calibration curves for carbon dioxide, carbon monoxide and methanol are illustrated i n figure 6.4. A l l three calibration curves show good linearity, w i t h R-squared values over 0.98. Equations relating the peak area to the amount o f carbon dioxide, carbon m o n o x ide and methanol are shown i n eqs. 6.3, 6.4 and 6.5, respectively. P r e l i m i n a r y calibrations, prior to installation o f the methanizer, indicated good linearity between 10 and 500 p p m carbon monoxide. Calibration curves were generated by measuring gas chromatogram peak area o f samples containing different amount o f either carbon monoxide, carbon d i o x i d e or methanol. The carbon monoxide and carbon dioxide samples were prepared by injecting different volumes o f certified gas containing 50 p p m of carbon m o n o x i d e or carbon d i o x ide. M e t h a n o l samples were prepared by m i x i n g different ratios o f a gas stream saturated with methanol and U H P h e l i u m . B a s e d on the temperature, the amount o f methanol was calculated, assuming gas stream was saturated w i t h methanol.  93  M o l e c u l a r Sieve 13x c o l u m n , F I D Detector, 30 c m / m i n ( S T P ) H e 3  Figure 6.3: Gas chromatogram o f C O containing sam  C o  =  0.00138A + 4.22  =  0.00115A - 1.30  CcHsOH =  0.00166A - 23.6  C  2  Ceo  94  140.0  20.0  0,0 •)  1  20,000  1  1  1  40,000  60,000'  80,000  Chromatogram Peak Area + Methanol  x C02  •  CO  Figure 6.4: C 0 , CO and C H O H calibration curves 2  3  95  1 100,000  Appendix III: Surface Molybdenum D u r i n g A s p e n simulations to obtain e q u i l i b r i u m data for the H e , C O , C 0 , C , M o , M o O , 2  M o 0 , M 0 O 3 , M o C and M o C system, an estimate for required amount o f M o . F o r equi2  2  l i b r i u m reactors i n A s p e n , the reactants must all be specified i n the feed stream. Thus, a rough estimate o f the amount o f M o present was calculated. The lowest amount available, was calculated assuming that the m o l y b d e n u m wire is non-porous and thus only m o l y b denum surface molecules are available for reaction. T h e highest amount available, was calculated assuming all the m o l y b d e n u m wire is available for reaction. Table 6.1 illustrates the data used to determine the amount of M o available for reaction. Based on the results illustrated i n table 6.1 and 6.2, the number of hours the reactor could operate w o u l d range from 100 minutes to 4.5 years. The 100 minutes result was obtained assuming that the surface is not porous and that only surface atoms are available  Table 6.1: M o surface moles rough estimate Description value units A t o m i c Radius  0.140  nm  A t o m i c cross section area  6.16E-20  m 2  M o wire Surface A r e a  0.039  m  M o "surface" A t o m s  6.4E17  atoms  M o "surface" moles  1.0E-6  moles  Feed C 0  50  ppm  4  seem  1E-8  mole/min  100  min  2  Feed Flowrate M o l a r Flowrate C 0  2  M o reaction time* * A s s u m i n g 100% M o conversion to M o 0  2  96  A  2  Table 6.2: M o total moles Description value  units  M o l e c u l a r Weight  95.94  g/mole  Weight M o used in reactor  2.2385  M o total moles  0.023  g moles  Feed C 0  50  ppm  4  seem  1E-8  mole/min  2  Feed Flowrate M o l a r Flowrate C 0  2  M o reaction time* years 4.5 * A s s u m i n g 100% M o conversion to M o 0 2  for reaction. T y p i c a l l y reactions take place for less than five minutes per synthesis. M o l y b denum being in excess o f C 0  2  i n the reactant stream is thus a reasonable assumption.  97  Appendix IV: Temperature Profile The temperature profile was measured for the m o l y b d e n u m reactor w i t h open ends and for the reactor with quartz w o o l plugged ends, w i t h a temperature setpoint o f 740°C. T h e position o f a K-type thermocouple was m o v e d from one end to the other o f the reactor, monitoring the temperature each 2 cm. A s illustrated i n figure 6.5, the addition o f quartz w o o l plugs improves the temperature gradient. T h e m o l y b d e n u m was place across a 10 cm length, from L = 2cm to L=12 cm. O v e r this length, the temperature varies from approximately 580°C to 7 4 0 ° C for the open ended reactor, and from approximately 6 8 0 ° C to 740°C for the plugged ends reactor. Thus the net effect o f the quartz w o o l plugs was to reduce the temperature variance from 160°C to 60° C.  98  800  700 •<  _^  600  O 500  400  o Open Ends  300 0  2  4  .  x Plugged Ends  6  8  10  12  14  L(cm) Figure 6.5: Reactor temperature profile, at 740°C  99  Appendix V: Process simulator H y s y s is suitable for m a i n l y gas/liquid phase reactions, with possible solid products. Carbon exists i n the H y s y s database w h i l e other solids can be custom created. Since A s p e n has a built i n database containing many solid compounds, including m o l y b d e n u m , it was selected to carry out the e q u i l i b r i u m reactions. First, to validate the simulator, A s p e n generated equilibrium data was compared to those reported i n literature, for the reactions o f methane w i t h m o l y b d e n u m and hydrogen w i t h carbon. We can see i n figures 6.7 and 6.6 that the equilibrium relationships generated using A s p e n are quite similar to those reported [81]. The equilibrium curves for the formation of d i m o l y b d e n u m carbide follow a similar pattern, however there is an offset on the temperature scale o f about 25 K . T h e equilibrium curves for the formation o f d i m o l y b d e n u m carbide follows a similar pattern, however there is an offset on the temperature scale o f about 100 K . A l t h o u g h the temperature difference is significant, the shape o f the curves are near identical. Thus A s p e n was used to generate e q u i l i b r i u m curves. T h e f o l l o w i n g description represents the steps required to set-up an A s p e n simulation to obtain equilibrium data for the M o , M o O , M o 0 , M 0 O 3 , C 0 , C O , 0 , C system. E q u i l i b r i u m curves 2  2  2  generated for other component systems follow a similar procedure and differ only i n the components used, temperature range and pressure range.  1. Setup Units: SI Stream Class: M I X C I S L D , for use when conventional solids are present with no  100  CH ^ C + 2H (b) CH + 2 • Mo ^ Mo C + 2H (a)  4  {s)  A  2  2  2  Obtained from [81] Figure 6.6: E q u i l i b r i u m relationships at atmospheric pressure M o - C - M o C - H - C H 4 2  101  2  •100%  5*  200  400  600  1000  800  1200  1400  1600  T0<) |•  CH4 + 2Mo = Mo2C t 2H2  CH4 = C f 2H2 |  (a) C # ^ C + 2H (b) C # + 2 • Mo ^ M o C + 2H 4  4  ( 8 )  2  2  2  Figure 6.7: Aspen generated equilibrium relationships at atmospheric pressure Mo-CM02C-H2-CH4  102  particle size distribution. 2. Possible Components: To begin with, here is a list of the compounds that can be present in the system, based on a feed of C 0 through a reactor containing Mo. Solids need to be defined as type 2  solid in Aspen, while gases are defined as type conventional Conventional: C 0 , CO, 0 , Ar 2  2  Solid: Mo, C, MoO, M o O , M o 0 , M o 0 , M 0 O 3 , M o C , MoC 2  s  2  2  5  2  Note: Components Mo 03, M 0 2 O 5 not part of database. 2  3. Properties Base Method: Peng-Robinson 4. Create Gibbs Reactor, with a feed stream and an equilibrium stream Set temperature: 273 K Set pressure: 2 bar 5. Define Feed stream Set composition of feed to desired mole fraction of each component Set temperature: 273 K Set pressure: 2 bar Set flowrate: 1 mole/sec 6. Model Analysis Tools Sensitivity Create new sensitivity analysis Define variables: all components in equilibrium stream in terms of mole fractions Temperature range 273-1573 K, 150 data points  103  The molar flow rate for each component was tabulated, copied to excel. From molar flowrate, molar fractions were easily calculated and plotted.  104  APPENDIX VI: Estimation of C 0  2  concentrations The exact amount o f C O 2 contained i n the target gas at Sherbrooke facilities is unknown. Sherbrooke facilities are not set-up to measure specific activity and by no means require high specific activity for their use o f carbon-11. Thus, their system is not optimized and no special precautions were taken to obtain high specific activity from their target. T h e range of reported specific activities is 0.1-16.5 C i / u m o l [45, 1, 21]. In practice, between 2001000 mCi C 0 2 w i l l be produced for each c l i n i c a l run. D u r i n g experiments at the C H U S , N  250 mCi was produced each run. T h e content o f C 0  2  entering the m o l y b d e n u m reactor  can be estimated based on the flowrate o f pushed used and the time required to eluted a l l the C 0 . A s can be seen i n table 6.3, this corresponds to between 28-560 p p m C 0 . N  2  2  The time required to elute a l l the C 0 n  2  is estimated to be between 2-5 minutes, at  flowrates between 25-200 cm /min and a pressure o f 2 bar. T h i s corresponds to a broad 3  range o f C 0  2  concentrations, roughly between 1 and 2,000 p p m C 0 , as can be seen in 2  table 6.3. Gases containing 50 p p m o f C 0 or 50 p p m C O were selected to represent 2  quantities used i n routine carbon-11 radiopharmaceutical synthesis.  Table 6.3: C Q concentration estimates S A (Ci/umol) C0 (mCi) umol C 0 Q (c m/min) 2  n  3  2  2  P (bar)  t (min)  2  ppm C 0  2  CHUS  0.1  250  2.5  25-200  2-5  28-560  Low S A  0.1  200-1000  2-10  25-200  2  2-5  22-2,200  High S A  16.5  200-1000  0.01-0.06  25-200  2  2-5  0.7-27  105  

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