1

 Understand how to assemble design data and create a preliminary data base  Able to implement the steps in creating flowsheets  Know how to select the principal pieces of equipment and to create a detailed process flowsheet, with a material and energy balance and a list of major equipment items.

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• Preliminary Database Creation – to assemble data to support the design • Experiments – to supply missing database items or verify crucial data • Preliminary Process Synthesis – to generate a “synthesis tree” of design alternatives • Development of Base-case Design – focusing on the most promising alternative(s) from the synthesis tree.

3

Thermophysical property data • physical properties • phase equilibria (VLE data) • Property prediction methods Environmental and safety data • toxicity data • flammability data Chemical Prices • e.g. as published in the Chemical

Marketing Reporter

Experiments • to check on crucial items 4

Synthesis of chemical processes involves:

 Selection of processing mode : continuous or batch  Fixing the chemical state of raw materials, products, and by-products, noting the differences between them.

 Process operations (unit operations) - flowsheet building blocks 5

Process Operation steps:

Eliminate differences in molecular types Distribute chemicals by matching sources and sinks Eliminate differences in composition Eliminate differences in temperature, pressure and phase Integrate tasks (combine tasks into unit operations) 6

Continuous Batch Fed-batch Batch-product removal 7

• Decide on the raw material and product specifications (

states

):  Mass (flow rate)  Composition (mole or mass fraction of each chemical species having a unique molecular type)  Phase (solid, liquid, or gas)   Form (e.g., particle-size distribution and particle shape) Temperature  Pressure 8

• Chemical reaction – Involves conversion, rates, etc., related to T and P at which the reaction are carried out • Separation of chemicals – resolve difference between the desired composition of a product stream and its source – method depends on the phase & physical properties • Phase separation • Change of temperature • Change of pressure • Change of phase • Mixing and splitting of streams and branches 9

Step Eliminate differences in molecular types Distribute chemicals by matching sources and sinks Eliminate differences in composition Eliminate differences in temperature, pressure and phase Integrate tasks (combine tasks into unit operations) Process Operation Chemical reaction Mixing Separation Temperature, pressure and phase change 10

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“An opportunity has arisen to satisfy a new demand for VCM, on the order of 800 million pounds per year, in a petrochemical complex on the Gulf Coast, given that an existing plant owned by the company produces one-billion pounds per year of this commodity chemical. Since VCM is an extremely toxic substance, it is recommended that all new facilities be designed carefully to satisfy governmental health and safety regulations.”

Chemical Acetylene Chlorine Molecular weight 26.04

70.91

1,2-Dichloroethane 98.96

Ethylene Hydrogen chloride Vinyl chloride 28.05

36.46

62.50

Chemical formula C 2 H 2 Cl 2 C 2 H 4 Cl 2 C C 2 2 HCl H H 3 4 Cl Chemical structure H - C  C - H Cl-Cl Cl Cl | | H-C-C-H | | H H H H C = C H H H-Cl H Cl C = C H H 13

 Direct chlorination of ethylene: C 2 H 4  Cl 2  C 2 H 3 Cl  HCl Advantages: – Attractive solution – Occurs spontaneously at a few hundred o C (3.1) Disadvantages: – Does not give a high yield of VC without simultaneously producing large amounts of by-products such as dichloroethylene – Half of the expensive chlorine is consumed to produce HCl by product, which may not be sold easily.

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 Hydrochlorination of acetylene: C 2 H 2  HCl  C 2 H 3 Cl (3.2) Advantages: – Exothermic reaction - potential solution – It provides a good conversion (98%) of C 2 H 2 VC in the presence of HgCl 2 catalyst impregnated in activated carbon at atmospheric pressure. – These are fairly moderate reaction conditions, and hence, this reaction deserves further study. 15

 Thermal cracking of C 2 H 4 Cl 2 from chlorination of C 2 H 4 : C C 2 H 4 2 H 4 Cl  2 Cl 2   C C 2 H 2 H 3 Cl 4  Cl 2 HCl C 2 H 4  Cl 2  C 2 H 3 Cl  HCl (3.3) (3.4) (3.1) Advantages: – Conversion in exothermic reaction (3.3) is  98% at 90 o C and 1 atm with a Friedel-Crafts catalyst such as FeCl 3 . – This intermediate is converted to vinyl chloride by thermal cracking according to the endothermic reaction (3.4), which occurs spontaneously at 500 o C with conversions as high as 65% Disadvantage: – Half of the expensive chlorine is consumed to produce HCl by-product, which may not be sold easily.

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 Thermal Cracking of C 2 H 4 Cl 2 from Oxychlorination of C 2 H 4 : C 2 H 4 C 2 H 4  2HCl  Cl 2 1 2  C 2 H 3 O 2 Cl  C 2 H 4  HCl Cl 2  H 2 O C 2 H 4  HCl  1 2 O 2  C 2 H 3 Cl  H 2 O (3.5) (3.4) (3.6) Advantages: – Highly exothermic reaction (3.5) achieves a 95% conversion in the presence of CuCl 2 catalyst, followed by pyrolysis step (3.4) – Excellent candidate when cost of HCl is low Disadvantages: – Economics dependent on cost of HCl 17

 Balanced Process for Chlorination of Ethylene: C C 2 2 H H 4 4   Cl 2  C 2HCl  2 1 2 H 4 O 2 Cl 2  C 2 H 4 Cl 2 2C 2 H 4 Cl 2  2 C 2 H 3 Cl  2HCl  H 2 O 2 C 2 H 4  Cl 2  1 2 O 2  2 C 2 H 3 Cl  H 2 O Advantages: – Combination of Reaction Paths 3 and 4 – All Cl 2 converted to VC – No by-products!

(3.3) (3.5) (3.4) (3.7) 18

 Reaction Path  is eliminated due its low selectivity.

 This leaves four alternative paths, to be compared first in terms of Gross Profit.

Chemical Bulk Prices

Chemical

Ethylene Hydrogen chloride Water Acetylene Chlorine Vinyl chloride Oxygen (air)

Cost (cents/lb)

30 80 18 35 25 0 0 19

Reaction path

 C 2 H 4 + Cl 2 = C 2 H 3 Cl + HCl lb-mole Molecular weight 1 28.05

1 70.91

1 62.50

1 36.46

lb 28.05

70.91

62.50

36.46

lb/lb of vinyl chloride 0.449

1.134

1 0.583

cents/lb 30 18 35 25 Gross profit = 35(1) + 25(0.583) - 30(0.449) - 18(1.134) = 15.69 cents/lb VC

Reaction Path



Overall Reaction

C 2 H 2 + HCl = C 2 H 3 Cl

Gross Profit (cents/lb of VC)

-16.00

 C 2 H 4 +Cl 2 = C 2 H 3 Cl + HCl 15.69

  C 2 H 4 + HCl + O 2 = C 2 H 3 Cl + H 2 O 2C 2 H 4 + Cl 2 + O 2 = 2C 2 H 3 Cl + H 2 O 6.96

11.32

20

Cl 2 113,400 lb/hr C 2 H 4 44,900 lb/hr Raw Materials Products C C 2 2 H H 4 4 , Cl + Cl 2 Direct Chlorination 2 C 2 H 4 C 2 Process Flowsheet?

4 2 Cl 2 C 2 H 3 Cl, HCl Pyrolysis C 2 H 3 Cl C 2 H 4 Cl 2 C 2 H 4 Cl 2  C 2 H 3 Cl + HCl HCl 58,300 lb/hr C 2 H 3 Cl 100,000 lb/hr • 100,000 lb/hr  800 Mil lb/yr @ 330 days/yr VC • On the basis of this principal

sink

, the HCl

sink

reagent

sources

and can be computed (each flow is 1,600 lbmol/h) 21

• A conversion of 100% of the C 2 H 4 reaction. is assumed in the chlorination 22

• Only 60% of the C 2 H 4 Cl 2 is converted to C 2 H 3 Cl & HCl • To satisfy the overall material balance, 158,300 lb/h of C 2 H 4 Cl 2 must produce 100,000 lb/h of C 2 H 3 Cl and 58,300 lb/h of HCl.

• A 60% conversion only produces 60,000 lb/h of VC.

• The additional C 2 H 4 Cl 2 needed is 105,500 lb/h.

• Its source is a recycle stream from the separation of C 2 H 3 Cl from unreacted C 2 H 4 Cl 2 , from a mixing operation, inserted to combine the two sources, to give a total 263,800 lb/h.

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• The effluent stream from the pyrolysis operation is the source for the C 2 H 3 Cl product, the HCl by-product, and the C 2 H 4 Cl 2 recycle. 24

• The product of the chlorination reaction is nearly pure C 2 H 4 Cl 2 , and requires no purification. • In contrast, the pyrolysis reactor conversion is only 60%, and one or more separation operations are required to match the required purities in the C 2 H 3 Cl and HCl sinks.

• One possible arrangement is given in the next slide 25

Chemical HCl C 2 H 3 Cl C 2 H 4 Cl 2 1 atm -84.8

-13.8

83.7

Boiling point (oC) 4.8 atm 12 atm -51.7

-26.2

33.1

146 70.5

193 26 atm 0 110 242 Critical constants T c ,  51.4

159 C 250 P c , atm 82.1

56 50 26

27

28

29

tPA is tissue plasminogen activator A recombinant, therapeutic protein - comprised of 562 amino acids 30

Pharmacology:     tPA activates plasminogen – to plasmin (an enzyme) plasmin dissolves fibrin formations that hold blood clots in place blood flow is re-established once the clot blockage dissolves important for patients with heart attacks (myocardial infarction) or stroke Business Strategy:     has been produced by Genentech (Activase TM ) since 1986 sells for $2,000/100 mg dose 2003 – Patent protection expires Design objective – manufacture generic form of tPA to sell for $200/dose 31

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Identify Reaction Paths – with help from the Biochemist

1. Mammalian Cells

tPA-DNA sequence + CHO cells  selected high expressing tPA-CHO cells (1) Selected tPA-CHO cells (“founder cells”) amplified to yield about 10 6 cells/mL – during R&D stage. These cells are frozen into 1 mL aliquots at - 70  C.

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Prepared in laboratory – stored in 1 mL aliquots at - 70 ° C Used as inoculum for the bio-reaction: tPA-CHO cells + HyQ PF-CHO media + O 2  Increased cell nos. (2) 0.39

 10 6 cells/mL-day 50 pg tPA/cell-day 0.2

 10 -12 mol O 2 /cell-hr As tPA-CHO cells reproduce, tPA secretes into liquid media solution.

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Project cost of chemicals produced or sold Chemical

tPA

Kg/Kg tPA

1

Cost, $/Kg

2,000,000



HyQ PF CHO powder media Water for injection (WFI) Air 287.2

2,228 46.8

233 0.12

+ 1,742 CO 2 3.7

1,447 tPA-CHO cells *

 $200/100 mg dose + $0.45/gal = $450/1,000 gal * Not included in gross profit estimate – related to cost of research, an operating cost.

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Gross Profit = 2,000,000 – (287.2

(46.8

 1,742)  233) – (2,228  0.12) – (3.7

 1,447) – = $1,846,000/Kg tPA Does not include operating costs (cost of research and cost of utilities) and investment cost - yet, high for a pharmaceutical - process synthesis proceeds at an accelerated pace 36

37

 tPA protein must be recovered from other proteins, cell debris, media, water, and gas emissions  Proteins lose activity (denature) at temperatures above ~ 0  C  Hence - entire separation process designed to operate at 4  C, slightly above freezing point of water.

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39

40

 Equipment items are selected – often combining operations into a single equipment item  Key decision – batch or continuous operation  80 Kg/yr tPA – batch mode  Select equipment sizes to produce 1.6 Kg/batch  i.e., 80/1.6 = 50 batch/yr  To allow for separation losses, produce 2.24 Kg/batch in the cultivators   Using 5,000 L vessel, 14 day/batch = cycle time Hence, run two batch trains in parallel  each producing 25 batch/yr 41

42

43

• Preliminary Database Creation – to assemble data to support the design • Experiments – to supply missing database items or verify crucial data • Preliminary Process Synthesis – to generate a “synthesis tree” of design alternatives • Development of Base-case Design – focusing on the most promising alternative(s) from the synthesis tree.

44