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Reaction path synthesis for environmental impact minimization
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Computers"chem. Engng, Vol. 21, Suppl., pp. $959-$964, 1997 © 1997 Elsevier Science Ltd All rights reserved Printed in GreatBritain
PII: S 0 0 9 8 - 1 3 5 4 ( 9 7 ) 0 0 1 7 3 - 7
0098-1354/97 $17.00+0.00
Reaction Path Synthesis For Environmental Impact Minimization A. Buxton, A.G. Livingston and E.N. Pistikopoulos* Centre for Process Systems Engineering, Dept. of Chemical Engineering Imperial College, London, SW7 2BY, U.K. A b s t r a c t - Reaction path synthesis, the generation of a network of alternative reaction routes for the manufacture of a desired product and the selection of an optimal route, represents a key step in arriving at environmentally sound process designs. In this paper a systematic procedure for organic reaction path synthesis is described in which minimum environmental impact considerations are incorporated in order to exploit the earliest opportunities for waste reduction. The size of the reaction path synthesis problem is reduced by decomposing it into a series of steps, each of which is approached in a guided way. This is achieved by first introducing a group based computer aided raw material and stoichiometric co-product design step. With the raw materials, stoichiometric co-products and product known, the reaction path synthesis problem is no longer open ended. Feasible stoichiometries between these materials are determined and promising candidates are identified according to the Methodology for Environmental Impact Minimization (Pistikopoulos et al., 1994).
INTRODUCTION
concentrated on technological alternatives with predetermined chemistry (Linninger et al., 1995; DouReaction path synthesis is a very large and comglas, c1994). plex problem. In order to identify promising reaction routes, reaction path synthesis tools must deal with a The central ideas behind our procedure are to relarge number of alternative chemistries and sufficient duce the size of the reaction path synthesis problem by decomposing it into a series of steps, each information to evaluate each one. Traditional approaches to reaction path synthesis of which is approached in a guided way, and to inhave concentrated on generating chemistries (Corey corporate environmental considerations in the route and Wipke, 1969; Ugi and Gillespie, 1971; Rotstein et selection exercise in order to exploit the earliest opal. 1982). Agnihotri and Motard (1980) divided these portunities for waste reduction. We adopt a group methods into two categories - logic-based systems, based approach to reaction path synthesis, achieving with their roots in mathematics and information- problem size reduction principally by introducing a based systems, with their roots in chemistry. How- raw material and co-product design step, exploiting ever, the relationships between the desired product the relationship between these compounds and the and the raw materials and stoichiometric co-products desired product. Our procedure includes both logic (which we will refer to collectively as co-materials) and information-based chemistry representation syshave not been exploited so that within these tools, tems in a way which capitalises on the advantages of the co-materials are not developed in a systematic both. way. Furthermore, there is a trade-off between the Aspects of the Methodology for Environmental Imgenerality of the tools (the ability to represent many pact Minimization, MEIM (Pistikopoulos et al., alternatives) and their predictive power (the ability to 1994) provide the framework for the environmental represent specific distinct reactions in detail) (Govind evaluation of alternatives. Using this approach, we and Powers, 1981), according to the representation incorporate environmental considerations and prinsystem employed. ciples from life cycle analysis in the route selection Recently, the issue of route selection, with or with- problem, so that the wastes associated with the inout explicit environmental objectives, has come puts to a process (raw materials, energy consumpto the forefront (Crabtree and E1-Halwagi, 1994; tion, capital, etc.) as well as the conventional process Fornari and Stephanopoulos, 1994; Knight, 1995; emissions are accounted for. This is achieved by (i) Mavrovouniotis and Bonvin, 1995). However, the expanding the conventional process boundary to inpotential of environmental evaluation of alternative clude all processes associated with raw material manreaction routes has not been fully explored. Other ufacture and energy generation, (ii) defining a set of synthesis approaches for waste minimization have pollution metrics (such as air, water pollution, global *To whom correspondence should be addressed; e-marl: [email protected] $959
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warming, ozone depletion etc.) in order to transform all process emissions (output and input) into a common currency with respect to environmental damage and (iii) embedding these metrics into our procedure. In this paper we introduce the foundations of our procedure and we concentrate on the issues of comaterial design and stoichiometry determination and evaluation. We illustrate the application of our method with an example problem: the synthesis of production routes for the pesticide 1-naphthyl-Nmethyl carbamate, also known as carbaryl. PROBLEM STATEMENT The reaction path synthesis problem for minimum environmental impact may be stated as follows: Given a desired product
Determine a set of candidate reaction routes and corresponding process technologies for the production of a fixed amount of the desired product which are promising both economically and in terms of minimum environmental impact. This problem has two key elements: (i) the generation of a set of alternative reaction routes with corresponding technologies and (ii) the evaluation of these routes and the selection of a subset of economically attractive, environmentally benign candidates. Each of these subproblems is very large because of the many alternative reaction routes and corresponding alternative process configurations which may be employed to produce the desired product. It is desireable to solve the subproblems simultaneously. However, this is difficult to achieve, as the traditional reaction path synthesis tools have revealed. Therefore, we propose a structured, stepwise procedure in which we decompose the reaction path synthesis problem in order to deal with its size. OUTLINE OF PROCEDURE The steps of our methodology are as follows for a fixed desiredproduct: (i) select co-material groups, (ii) determine a set of candidate co-materials using group based molecular design techniques, (iii) identify a set of promising candidate stoichiometries using a logicbased representation system and an optimization selection procedure incorporating aspects of the MEIM, (iv) generate corresponding mechanisms using functional group transformations and so introduce competing reactions, (v) evaluate the mechanism steps in detail using the MEIM to make a final selection. The key to our procedure is the introduction of the co-material design steps. Recognising that much organic chemistry essentially consists of reorganising functional groups (through additions, substitutions and eliminations), we expect our co-materials to contain (at least) the group structures present in the desired product. Accordingly, we systematically design our candidate co-materials according to the group structure of the product, the types of chemistries we wish to consider (e.g. aliphatic or aromatic) and other considerations (such as property constraints) using a group based computer aided molecular design technique.
We use groups, rather than atoms, as our molecular building blocks for several reasons. First of all, this considerably reduces the combinatorial size of the molecular generation problem without much loss of generality - very many organic compounds can be constructed using only a small number of groups. Secondly, with appropriate group bonding restrictions (see Co-Material Desi#n) such a method provides a short cut to structurally and chemically feasible molecules, so significantly reducing molecular screening requirements. Finally, a suitable choice of groups gives direct access to the thermodynamic and environmental properties we need through group contribution methods. With the co-materials and product known the reaction path synthesis problem is no longer open ended and is therefore considerably reduced. Now we must bridge the gap between these materials with feasible stoichiometries and corresponding reaction mechanisms and then make our final route selection. The first step towards this is to identify feasible overall stoichiometries, without mechanisms, involving our co-materials and leading to our product. In order to achieve this we employ a logic-based chemistry representation system and an optimization based procedure, incorporating aspects of MEIM, to identify good candidate stoichiometries among the alternatives according to economic, thermodynamic and environmental impact criteria (see Stoichiometry Selection). Now we have a set of promising stoichiometries involving some of our candidate raw materials, our product and some stoichiometric co-products. From this position we can employ an information based approach in order to generate the underlying reaction mechanisms using functional group transformations based on real chemistry. We can then use the MEIM in its full form to analyse our candidate routes within an optimization framework and make the final selection. In this work we concentrate on the identification of economically attractive and environmentally benign candidate stoichiometries, divorced from any process technology. In future publications we will consider the problem of determining the underlying chemical mechanisms and the optimal process configurations corresponding to our candidate stoichiometries. CO-MATERIAL DESIGN Co-material design is the key in reducing the reaction path synthesis problem to a manageable size. Our aim is to select a set of co-material groups (see New Rules for Co- Material Design) and then to generate a set of structurally and chemically feasible co-materials from these groups with the minimum screening requirement. We must also introduce additional structural restrictions which are pertinent to the reaction path synthesis problem. We employ the molecular design algorithm within the CAMD approach of Gani et al. (1991), later updated by Constantinou et al. (1995), incorporating some
PSE '97-ESCAPE-7 Joint Conference new rules of our own to design our set of co-materials. CAMD is based on a system of group classification and categorisation. The class of each group represents the number of free attachments available to the group and the category signifies the level of restriction for bonding with other groups - the higher the category the tighter the restrictions. The molecular design algorithm is based on a set of conditions which ensure structural and chemical feasibility, firstly by ensuring that the complete compound has zero valency and secondly that it obeys the principles of chemistry. These principles have been embodied in a set of rules which determine the maximum permissible number of groups from any category which can be present in a molecule and the permissible combinations of groups from the different categories. These rules are divided into three sets; a set each for acyclic, cyclic and aromatic molecules. The molecular design algorithm has been developed to systematically generate all molecules which satisfy these conditions.
New Rules for Co-Material Design Gani's approach includes over one hundred groups and can potentially generate thousands of feasible molecules (Constantinou et al., 1995), not all of which are interesting from a reaction path synthesis point of view. In order to reduce the number of molecules which are passed to the stoichiometry selection step we introduce three new sets of rules for co-material .design. Our rules are based mainly on engineering and chemical insight, rather than on property constraints, as in the conventional molecular design problem. The first set of rules is aimed at group pre-selection. Group pre-selection is the first step towards designing co-material molecules and has the most direct effect on the number of molecules we generate. We use the following simple rules to guide our group preselection: (i) include the groups present in the product, (ii) include groups present in any existing industrial raw materials, co-products or by-products, (iii) include groups which provide the basic building blocks for the functionalities of the product or of similar functionalities, (iv) select the group sets for the desired chemistry (cyclic, acyclic or aromatic), (v) reject groups which violate property restrictions (e.g. chloro groups may violate environmental restrictions - Gani et al., 1991). The second set of rules provides additional structural restrictions on the co-material molecules according to the structure of the product. This set is incorporated in the co-material design procedure so that undesireable structures are not generated only to be rejected later: (i) upper limit on the number of groups in the co-materials according to the number in the product - industrial co-materials are generally not signif-
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icantly larger than the product, (ii) upper limit on the number of substituents, substituted sites or functionalities - in general industrial co-materials are not significantly more complex than the product. The third set of rules are chemistry based screening rules, applied after the molecules have been generated. Rules (iii) and (iv) are in fact implemented within the stoichiometry selection procedure: (i) since we restrict ourselves to reactions involving only functional group transformations we reject molecules in which the carbon skeleton must be altered in order to achieve the product, (ii) restrict the number of members from any homologous series, (iii) disallow certain combinations of raw materials, (iv) impose role specification constraints on molecules (e.g. a particular species may be designated as a raw material only).
Additional Molecules During addition, substitution and elimination reactions some simple molecules which do not feature in CAMD may be generated or consumed. We introduce the following set of additional co-material molecules from which we may select a subset to be included in our stoichiometries.
a) H20
b) O2
c) H2
d) CO2
e) HCI
a) water b) oxygen c) hydrogen d) carbon dioxide e) hydrogen chloride STOICHIOMETRY
SELECTION
At this stage, our aim is to identify stoichiometries which link our co-materials to our product and which exhibit minimum environmental impact subject to economic and thermodynamic constraints. In order to do this, we examine the environmental performance of the stoichiometries at the reaction equilibrium position. The equilibrium position is located using the relationship between the Gibbs free energy change of reaction and the reaction equilibrium constant, the value of which is determined by the composition of the reaction mixture. The equilibrium position indicates the best possible conversion for any stoichiometry and therefore the maximum economic potential. We employ a cost constraint to reject reactions which do not exhibit promising economics (i.e. profit _> 0) at equilibrium. The overall mathematical model for stoichiometry selection (omitted here due to space limitations) corresponds to a large, non-convex, mixed-integer nonlinear programming (MINLP) problem. While ongoing research is aimed directly at solving this problem globally, a two step sequential solution strategy is adopted in this work to the determination and evaluation of stoichiometries, as follows.
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Stoichiometry Determination The first step - stoichiometry determination - can be achieved with a linear formulation. We write an atom balance for our co-materials and product as a system of linear equations (Rotstein et al, 1982) of which the solutions are vectors of stoichiometric coefficients. We then employ guided enumeration to extract stoichiometries from this system. From a process point of view we are more interested in simple stoichiometries, with few reactants and coproducts, than in complex ones. Clearly, the more molecules we have the more complex the reaction and particularly the separation processes must become. Accordingly, we formulate the stoichiometry determination problem as an optimization problem in which our objective is to minimise the sum of the magnitudes of the stoichiometric coefficients and we impose a (case dependent) upper limit on the number of molecules to be involved in the stoichiometries. We introduce constraints so that the stoichiometric coefficients take whole number values, integer cuts to exclude side reactions and we solve the problem iteratively, introducing integer cuts to exclude previous solutions as we go. In this way, we enumerate the stoichiometries starting with the simplest first. This formulation represents our guided enumeration approach.
following the Bhopal disaster. UCIL's process involved the raw materials 1-naphthol and methyl isocyante, a toxic substance with a PEL of 0.02ppm. Under disputed circumstances, 45 tons of methyl isocyanate underwent a chemical reaction and were released, killing approximately 2,500 people in the vicinity of the plant and resulting in some 300,000 additional casualties. The search for a production route involving more innocuous reactants is the motivation for this case study (Crabtree and E1-Halwagi, 1994).
Group Pre-selection Carbaryl can in fact be made with or without methyl isocyanate (Worthy, 1985). The two alternative industrial chemistries are shown below (Figures 1 and 2). CH3NH2
"J"
COCI2
Methyl Amine
~
CH3 - N ffiC ffiO
Phosgene
"{-
"J"
2 HCI
Methyl Isocysaate
CH3-- N~CffiO
~
~
H
O--H
O--C ~ ~CH 3 n O .
I-Naphthol
Cat'beryl (l-NaphthaJenyl Methyl Carbamate)
Figure 1: Methyl Isocyanate (Bhopal) Route
Stoichiometry Evaluation The second step - stoichiometry evaluation - involves equilibrium analysis of each reaction stoichiometry. Since the stoichiometries are now known, this reduces to a non-linear programming (NLP) problem. Our objective is the minimization of the environmental impact associated with each stoichiometry, subject to the aforementioned cost and thermodynamic constraints. In order to estimate the impact we assume 5% loss of reactor effluent by unavoidable leakage. We measure the impact in terms of the critical water mass (CTWM, Pistikopoulos et al., 1994). We solve the problem to determine the equilibrium composition and reaction temperature which correspond to the minimum environmental impact for each stoichiometry. The thermodynamic and environmental properties we require are calculated from group contributions (Van Krevelen et al., 1951; Gao et al., 1992). Finally we rank our stoichiometries according to economics and environmental impact in order to identify the most promising candidates. The mathematical details of our approach are reported elsewhere (Buxton et al., 1996).
+
COCI~
~
~
O--H
+ _
C
It O
~
"t-
HCI
O--C ~CI II O 1-Naphthalenyl Chloroformate
CI
CH3Nll:2
~
H l
O _ C ~ N~CH3 fl O Carlmryl
Figure 2: Non-Methyl Isocyanate Route We make our group pre-selection according to our New Rules for Co-Material Design (see Co-Material Design), restricting ourselves to the simplest set of groups which represent these molecules and the functional groups of interest. Employing the functional group definitions of Gani et al. (1991), our set of selected groups (12 in all) is then: (i) aromatic groups AC-, ACH, ACC1, ACOH; (ii) other groups °CH3, CH3NH<, C H 3 N H 2 - , - C O O - , - C H O , - C O 2 H , - O H , -C1.
Co-Material Design
We construct our co-material molecules according to Gani's molecular design procedure, (Gani et al., 1991) EXAMPLE PROBLEM PRODUCTION incorporating our new rules. Specifically, we introOF 1-NAPHTI-IALENYL METHYL duce the following structural and chemistry-based reCARBAMATE strictions: (i) we impose upper limits on the numProduct Identification bers of groups in our non-aromatic molecules so that 1-naphthalenyl methyl carbamate, also known as 'car- we retain the simplest set of non-aromatic molecules baryl' was employed as a pesticide (Worthy, 1985). It which contain functional groups of interest, (ii) we was manufactured under the trade name SEVIN by impose an upper limit of 14 groups within our aroUnion Carbide India, Limited (UCIL) in Bhopal un- matic molecules since it is unlikely that we would til December, 1984 when production was terminated synthesise our product from a more complex molecule -
PSE '97-ESCAPE-7 Joint Conference
(earbarvl contains 14 groups), (iii) we allow only monosubstituted aromatic molecules (since the product is monosubstituted), (iv) we eliminate all molecules of which the carbon skeleton must be altered in order to achieve the product (e.g. we reject all benzyl (single ring) structures since we do not wish to be concerned with contructing the naphthyl (double ring) group). By applying these criteria we reduce our set of molecules to fifteen in total (see Figures 3 and 4).
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in any feasible stoichiometry. Thirteen stoichiometries meet this constraint, these routes are shown in Table 1, ranked according to their economic potential. The original Union Carbide industrial chemistry and one of the routes generated by Crabtree and E1Halwagi (1994) were reproduced, the other two routes put forward by Crabtree and E1-Halwagi were eliminated by our cost constraint.
&o-Material Design Results :~
CI a)
OH
b)
H~N~cH3 d)
c)
_ C ~ OH n O
O_c~CI II O 13
e)
~ ~. ~ ~ t.- ~. ~ ~. ~ .~ ~ e~ "~
O--C ~ ~CH 3 II O g)
Figure 3: Aromatic Molecules a) Naphthalene, b) 1-Chloronaphthalene c) 1-Naphthol, d) N-Methyl-l-Naphthylamine e) 1-Naphthalenyl Hydroxyformate f) 1-Naphthalenyl Chloroformate g) Carbaryl
CI2
CH3C |
CH3OH
CI--C~ H
H
a)
b)
c)
d)
H-- C ~ N ~ CH 3 II
CH3NH2
CI~C_. O CI
e)
CH3-- N = C = O
f)
,.7
,
"7"7"7"7
"77
"7,
7
"7,
O
h)
g)
Figure 4: Aliphatic and Other Molecules a) Chlorine, b) Methyl Chloride, c) Methanol d) Chloromethanal, e) Methylamine, f) Phosgene g) Methyl Isocyanate, h) Methyl Formamide
1 2 3 4
The isocyanate group and phosgene do not appear in Gani's method, so we add methyl isocyanate and phosgene to class zero (complete molecules).
5
Additional Molecules We introduce four additional co-material molecules: a) H 2 0
b) 02
c) H2
d) HC1
a) water b) oxygen c) hydrogen d) hydrogen chloride
6 7
8 9 10
Oxygen Hydrogen Hydrogen Chloride 1-Naphthol Chloroformate Methyl Formamide Water Methylamine Phosgene Methyl Isocyanate 1-Naphthol
11 12 13 14 15 16 17 18 19
Carbaryl Naphthalene 1-Chloronaphthalene N-methyl-l-Naphthyl Amine 1-Naphthalenyl Hydroxyformate Chlorine Chloromethane Methanol Chloromethanal
Table 1: Stoichiometry Selection Results
All of the alternative stoichiometries exhibit more promising economics than the Bhopal chemistry and more than half also exhibit lower environmental imStoichiometry Selection Results pact. Stoichiometries 5,6 and 12 represent the best The solutions from the stoichiometry selection pro- compromise solutions, with both promising economics grams are presented below in the form of a table of and low environmental impact. stoichiometric coefficients; blank spaces indicate zero Stoichiometries involving methyl isocyante (specie 9) coefficients. A basis production rate of 1 mol/hr of and/or 1-chloronaphthalene (specie 13) as raw macarbaryl was employed. An upper limit of six was im- terials exhibit relatively high environmental impact, posed on the number of molecules Nmot to be involved and should therefore be avoided.
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$964 APPENDIX
This work has employed the following assumptions (i) we assume that the Gibbs free energies of formation and of reaction are linear with temperature, (ii) we assume that the group contribution techniques we have used to obtain the Gibbs free energies of formation and toxicities of our molecules are suitable for all of our molecule (iii) we assume 5% of reactor effluent flow by mass is released by unavoidable leakage, (iv) we assume that all emissions are to the water phase, we do not model pollutant fate (v) we do not consider wastes which do not arise directly from the process chemistry (e.g. solvents and wash water), (vi) all generated molecules are chemically feasible, (vii) group based raw material design provides all interesting co-materials, (viii) we have applied limits to the numbers of groups to be allowed in any co-material and the number of functionalities, (ix) the additional molecules we require to complete our stoichiometries are not systematically designed or selected, (x) we apply an upper limit to the number of molecules which may be involved in any stoichiometry, (xi) side reactions are excluded by integer cuts, (xii) do not consider competing reactions at this stage, (xii) we assume low pressure (1 atm) gas phase reaction and we make the perfect gas assumption, (xiii) we employ a hierarchical screening procedure: economics, thermodynamics, then environmental impact, (xiv) we cost only the products and the reactants, no process equipment or operating costs (xv) we do not consider solvents, catalysts or reagents. Current research efforts are aimed at relaxing some of these assumptions.
REFERENCES Agnihotri, R.B. and R.L. Motard (1980). Reaction Path Synthesis in Industrial Chemistry. Compu-
ter Applications to Chemical Process Design and Simulation, ACS Symposium Series 124, 193. Buxton, A., A.G. Livingston and E.N. Pistikopoulos (1996). Reaction Path Synthesis for Minimum Environmental Impact. Manuscript in Pre-
paration, Imperial College. Corey, E.J. and W.T. Wipke (1969). ComputerAssisted Design of Complex Organic Syntheses. Science 166. Constantinou, L., K. Baghepour, R. Gani, J. Klein and D. T. Wu (1995). Computer Aided Product Design: Problem Formulations, Methodology and Applications. Computers chem. Engng (in print) Crabtree, E.W. and M.M. E1-Halwagi (1994). Synthesis of Environmentally Acceptable Reactions.
Pollution Prevention via Process and Product Modifications, AIChE Symposium Series 90, 117-127.
Douglas. J. M. (c1994). Process Alternatives for Pollution Prevention. Communication. University of Massachusetts. Fornari, T. and G. Stephanopoulos (1994). Synthesis of Chemical Reaction Paths: Economic and Specification Constraints. Chemical Engineering Communications 129, 159-182. Gani, R., B. Neilsen and A. Fredenslund (1991). A Group Contribution Approach to Computer Aided Molecular Design. AIChE Jounal 37(9), 1318-1332. Gao, C., R. Govind and H.H. Tabak (1992). Application of the Group Contribution Method for Predicting the Toxicity of Organic Chemicals. Environmental Toxicology and Chemistry 11,631-636. Govind, R. and G.J. Powers (1981). Studies in Reaction Path Synthesis. AIChE Journal 27(3), 429-442. Knight, J.P. (1995). Computer-Aided Tools to Link Chemistry and Design in Process Development. PhD Thesis, Massachusetts Institute of Technology. Linninger, A.A., Shahin A. Ali, E. Stephanopoulos, C. Hun and George Stephanopoulos (1995). Synthesis and Assessment of Batch Processes for Pollution Prevention. FOCAPD, AIChE Symposium Series 91, 41-51. Mavrovouniotis, M.L. and D. Bonvin (1995). Design of Reaction Paths. FOCAPD, AIChE Symposium Series 91, 41-51. Pistikopoulos, E. N., S. K. Stefanis and A. G. Livingston (1994). A Methodology for Minimum Environmental Impact Analysis. AIChE Symposium Series 90(303), 139-151. Rotstein, E., D. Resasco and G. Stephanopoulos (1982). Studies on the Synthesis of Chemical Reaction Paths - I. Chemical Engineering Science 37(9), 1337-1352. Ugi, I. and P. Gillespie (1971). Chemistry and Logical Structure. 3. Representation of Chemical Systems and Interconversions by BE matrices and their Transformation Properties. Agnew.Chem.Ind.Ed. Engl 10, 914. Van Krevelen, D.W. and H.A.G. Chermin (1951). Estimation of the free enthalpy (Gibbs free energy) of formation of organic compounds from group contributions. Chemical Engineering Science 1, 66-80. Worthy, W. (1985). Methyl Isocyanate: The Chemistry of a Hazard. Chemical and Engineering News 63(6), 27-33.
Pergamon
Computers"chem. Engng, Vol. 21, Suppl., pp. $959-$964, 1997 © 1997 Elsevier Science Ltd All rights reserved Printed in GreatBritain
PII: S 0 0 9 8 - 1 3 5 4 ( 9 7 ) 0 0 1 7 3 - 7
0098-1354/97 $17.00+0.00
Reaction Path Synthesis For Environmental Impact Minimization A. Buxton, A.G. Livingston and E.N. Pistikopoulos* Centre for Process Systems Engineering, Dept. of Chemical Engineering Imperial College, London, SW7 2BY, U.K. A b s t r a c t - Reaction path synthesis, the generation of a network of alternative reaction routes for the manufacture of a desired product and the selection of an optimal route, represents a key step in arriving at environmentally sound process designs. In this paper a systematic procedure for organic reaction path synthesis is described in which minimum environmental impact considerations are incorporated in order to exploit the earliest opportunities for waste reduction. The size of the reaction path synthesis problem is reduced by decomposing it into a series of steps, each of which is approached in a guided way. This is achieved by first introducing a group based computer aided raw material and stoichiometric co-product design step. With the raw materials, stoichiometric co-products and product known, the reaction path synthesis problem is no longer open ended. Feasible stoichiometries between these materials are determined and promising candidates are identified according to the Methodology for Environmental Impact Minimization (Pistikopoulos et al., 1994).
INTRODUCTION
concentrated on technological alternatives with predetermined chemistry (Linninger et al., 1995; DouReaction path synthesis is a very large and comglas, c1994). plex problem. In order to identify promising reaction routes, reaction path synthesis tools must deal with a The central ideas behind our procedure are to relarge number of alternative chemistries and sufficient duce the size of the reaction path synthesis problem by decomposing it into a series of steps, each information to evaluate each one. Traditional approaches to reaction path synthesis of which is approached in a guided way, and to inhave concentrated on generating chemistries (Corey corporate environmental considerations in the route and Wipke, 1969; Ugi and Gillespie, 1971; Rotstein et selection exercise in order to exploit the earliest opal. 1982). Agnihotri and Motard (1980) divided these portunities for waste reduction. We adopt a group methods into two categories - logic-based systems, based approach to reaction path synthesis, achieving with their roots in mathematics and information- problem size reduction principally by introducing a based systems, with their roots in chemistry. How- raw material and co-product design step, exploiting ever, the relationships between the desired product the relationship between these compounds and the and the raw materials and stoichiometric co-products desired product. Our procedure includes both logic (which we will refer to collectively as co-materials) and information-based chemistry representation syshave not been exploited so that within these tools, tems in a way which capitalises on the advantages of the co-materials are not developed in a systematic both. way. Furthermore, there is a trade-off between the Aspects of the Methodology for Environmental Imgenerality of the tools (the ability to represent many pact Minimization, MEIM (Pistikopoulos et al., alternatives) and their predictive power (the ability to 1994) provide the framework for the environmental represent specific distinct reactions in detail) (Govind evaluation of alternatives. Using this approach, we and Powers, 1981), according to the representation incorporate environmental considerations and prinsystem employed. ciples from life cycle analysis in the route selection Recently, the issue of route selection, with or with- problem, so that the wastes associated with the inout explicit environmental objectives, has come puts to a process (raw materials, energy consumpto the forefront (Crabtree and E1-Halwagi, 1994; tion, capital, etc.) as well as the conventional process Fornari and Stephanopoulos, 1994; Knight, 1995; emissions are accounted for. This is achieved by (i) Mavrovouniotis and Bonvin, 1995). However, the expanding the conventional process boundary to inpotential of environmental evaluation of alternative clude all processes associated with raw material manreaction routes has not been fully explored. Other ufacture and energy generation, (ii) defining a set of synthesis approaches for waste minimization have pollution metrics (such as air, water pollution, global *To whom correspondence should be addressed; e-marl: [email protected] $959
$960
PSE '97-ESCAPE-7 Joint Conference
warming, ozone depletion etc.) in order to transform all process emissions (output and input) into a common currency with respect to environmental damage and (iii) embedding these metrics into our procedure. In this paper we introduce the foundations of our procedure and we concentrate on the issues of comaterial design and stoichiometry determination and evaluation. We illustrate the application of our method with an example problem: the synthesis of production routes for the pesticide 1-naphthyl-Nmethyl carbamate, also known as carbaryl. PROBLEM STATEMENT The reaction path synthesis problem for minimum environmental impact may be stated as follows: Given a desired product
Determine a set of candidate reaction routes and corresponding process technologies for the production of a fixed amount of the desired product which are promising both economically and in terms of minimum environmental impact. This problem has two key elements: (i) the generation of a set of alternative reaction routes with corresponding technologies and (ii) the evaluation of these routes and the selection of a subset of economically attractive, environmentally benign candidates. Each of these subproblems is very large because of the many alternative reaction routes and corresponding alternative process configurations which may be employed to produce the desired product. It is desireable to solve the subproblems simultaneously. However, this is difficult to achieve, as the traditional reaction path synthesis tools have revealed. Therefore, we propose a structured, stepwise procedure in which we decompose the reaction path synthesis problem in order to deal with its size. OUTLINE OF PROCEDURE The steps of our methodology are as follows for a fixed desiredproduct: (i) select co-material groups, (ii) determine a set of candidate co-materials using group based molecular design techniques, (iii) identify a set of promising candidate stoichiometries using a logicbased representation system and an optimization selection procedure incorporating aspects of the MEIM, (iv) generate corresponding mechanisms using functional group transformations and so introduce competing reactions, (v) evaluate the mechanism steps in detail using the MEIM to make a final selection. The key to our procedure is the introduction of the co-material design steps. Recognising that much organic chemistry essentially consists of reorganising functional groups (through additions, substitutions and eliminations), we expect our co-materials to contain (at least) the group structures present in the desired product. Accordingly, we systematically design our candidate co-materials according to the group structure of the product, the types of chemistries we wish to consider (e.g. aliphatic or aromatic) and other considerations (such as property constraints) using a group based computer aided molecular design technique.
We use groups, rather than atoms, as our molecular building blocks for several reasons. First of all, this considerably reduces the combinatorial size of the molecular generation problem without much loss of generality - very many organic compounds can be constructed using only a small number of groups. Secondly, with appropriate group bonding restrictions (see Co-Material Desi#n) such a method provides a short cut to structurally and chemically feasible molecules, so significantly reducing molecular screening requirements. Finally, a suitable choice of groups gives direct access to the thermodynamic and environmental properties we need through group contribution methods. With the co-materials and product known the reaction path synthesis problem is no longer open ended and is therefore considerably reduced. Now we must bridge the gap between these materials with feasible stoichiometries and corresponding reaction mechanisms and then make our final route selection. The first step towards this is to identify feasible overall stoichiometries, without mechanisms, involving our co-materials and leading to our product. In order to achieve this we employ a logic-based chemistry representation system and an optimization based procedure, incorporating aspects of MEIM, to identify good candidate stoichiometries among the alternatives according to economic, thermodynamic and environmental impact criteria (see Stoichiometry Selection). Now we have a set of promising stoichiometries involving some of our candidate raw materials, our product and some stoichiometric co-products. From this position we can employ an information based approach in order to generate the underlying reaction mechanisms using functional group transformations based on real chemistry. We can then use the MEIM in its full form to analyse our candidate routes within an optimization framework and make the final selection. In this work we concentrate on the identification of economically attractive and environmentally benign candidate stoichiometries, divorced from any process technology. In future publications we will consider the problem of determining the underlying chemical mechanisms and the optimal process configurations corresponding to our candidate stoichiometries. CO-MATERIAL DESIGN Co-material design is the key in reducing the reaction path synthesis problem to a manageable size. Our aim is to select a set of co-material groups (see New Rules for Co- Material Design) and then to generate a set of structurally and chemically feasible co-materials from these groups with the minimum screening requirement. We must also introduce additional structural restrictions which are pertinent to the reaction path synthesis problem. We employ the molecular design algorithm within the CAMD approach of Gani et al. (1991), later updated by Constantinou et al. (1995), incorporating some
PSE '97-ESCAPE-7 Joint Conference new rules of our own to design our set of co-materials. CAMD is based on a system of group classification and categorisation. The class of each group represents the number of free attachments available to the group and the category signifies the level of restriction for bonding with other groups - the higher the category the tighter the restrictions. The molecular design algorithm is based on a set of conditions which ensure structural and chemical feasibility, firstly by ensuring that the complete compound has zero valency and secondly that it obeys the principles of chemistry. These principles have been embodied in a set of rules which determine the maximum permissible number of groups from any category which can be present in a molecule and the permissible combinations of groups from the different categories. These rules are divided into three sets; a set each for acyclic, cyclic and aromatic molecules. The molecular design algorithm has been developed to systematically generate all molecules which satisfy these conditions.
New Rules for Co-Material Design Gani's approach includes over one hundred groups and can potentially generate thousands of feasible molecules (Constantinou et al., 1995), not all of which are interesting from a reaction path synthesis point of view. In order to reduce the number of molecules which are passed to the stoichiometry selection step we introduce three new sets of rules for co-material .design. Our rules are based mainly on engineering and chemical insight, rather than on property constraints, as in the conventional molecular design problem. The first set of rules is aimed at group pre-selection. Group pre-selection is the first step towards designing co-material molecules and has the most direct effect on the number of molecules we generate. We use the following simple rules to guide our group preselection: (i) include the groups present in the product, (ii) include groups present in any existing industrial raw materials, co-products or by-products, (iii) include groups which provide the basic building blocks for the functionalities of the product or of similar functionalities, (iv) select the group sets for the desired chemistry (cyclic, acyclic or aromatic), (v) reject groups which violate property restrictions (e.g. chloro groups may violate environmental restrictions - Gani et al., 1991). The second set of rules provides additional structural restrictions on the co-material molecules according to the structure of the product. This set is incorporated in the co-material design procedure so that undesireable structures are not generated only to be rejected later: (i) upper limit on the number of groups in the co-materials according to the number in the product - industrial co-materials are generally not signif-
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icantly larger than the product, (ii) upper limit on the number of substituents, substituted sites or functionalities - in general industrial co-materials are not significantly more complex than the product. The third set of rules are chemistry based screening rules, applied after the molecules have been generated. Rules (iii) and (iv) are in fact implemented within the stoichiometry selection procedure: (i) since we restrict ourselves to reactions involving only functional group transformations we reject molecules in which the carbon skeleton must be altered in order to achieve the product, (ii) restrict the number of members from any homologous series, (iii) disallow certain combinations of raw materials, (iv) impose role specification constraints on molecules (e.g. a particular species may be designated as a raw material only).
Additional Molecules During addition, substitution and elimination reactions some simple molecules which do not feature in CAMD may be generated or consumed. We introduce the following set of additional co-material molecules from which we may select a subset to be included in our stoichiometries.
a) H20
b) O2
c) H2
d) CO2
e) HCI
a) water b) oxygen c) hydrogen d) carbon dioxide e) hydrogen chloride STOICHIOMETRY
SELECTION
At this stage, our aim is to identify stoichiometries which link our co-materials to our product and which exhibit minimum environmental impact subject to economic and thermodynamic constraints. In order to do this, we examine the environmental performance of the stoichiometries at the reaction equilibrium position. The equilibrium position is located using the relationship between the Gibbs free energy change of reaction and the reaction equilibrium constant, the value of which is determined by the composition of the reaction mixture. The equilibrium position indicates the best possible conversion for any stoichiometry and therefore the maximum economic potential. We employ a cost constraint to reject reactions which do not exhibit promising economics (i.e. profit _> 0) at equilibrium. The overall mathematical model for stoichiometry selection (omitted here due to space limitations) corresponds to a large, non-convex, mixed-integer nonlinear programming (MINLP) problem. While ongoing research is aimed directly at solving this problem globally, a two step sequential solution strategy is adopted in this work to the determination and evaluation of stoichiometries, as follows.
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Stoichiometry Determination The first step - stoichiometry determination - can be achieved with a linear formulation. We write an atom balance for our co-materials and product as a system of linear equations (Rotstein et al, 1982) of which the solutions are vectors of stoichiometric coefficients. We then employ guided enumeration to extract stoichiometries from this system. From a process point of view we are more interested in simple stoichiometries, with few reactants and coproducts, than in complex ones. Clearly, the more molecules we have the more complex the reaction and particularly the separation processes must become. Accordingly, we formulate the stoichiometry determination problem as an optimization problem in which our objective is to minimise the sum of the magnitudes of the stoichiometric coefficients and we impose a (case dependent) upper limit on the number of molecules to be involved in the stoichiometries. We introduce constraints so that the stoichiometric coefficients take whole number values, integer cuts to exclude side reactions and we solve the problem iteratively, introducing integer cuts to exclude previous solutions as we go. In this way, we enumerate the stoichiometries starting with the simplest first. This formulation represents our guided enumeration approach.
following the Bhopal disaster. UCIL's process involved the raw materials 1-naphthol and methyl isocyante, a toxic substance with a PEL of 0.02ppm. Under disputed circumstances, 45 tons of methyl isocyanate underwent a chemical reaction and were released, killing approximately 2,500 people in the vicinity of the plant and resulting in some 300,000 additional casualties. The search for a production route involving more innocuous reactants is the motivation for this case study (Crabtree and E1-Halwagi, 1994).
Group Pre-selection Carbaryl can in fact be made with or without methyl isocyanate (Worthy, 1985). The two alternative industrial chemistries are shown below (Figures 1 and 2). CH3NH2
"J"
COCI2
Methyl Amine
~
CH3 - N ffiC ffiO
Phosgene
"{-
"J"
2 HCI
Methyl Isocysaate
CH3-- N~CffiO
~
~
H
O--H
O--C ~ ~CH 3 n O .
I-Naphthol
Cat'beryl (l-NaphthaJenyl Methyl Carbamate)
Figure 1: Methyl Isocyanate (Bhopal) Route
Stoichiometry Evaluation The second step - stoichiometry evaluation - involves equilibrium analysis of each reaction stoichiometry. Since the stoichiometries are now known, this reduces to a non-linear programming (NLP) problem. Our objective is the minimization of the environmental impact associated with each stoichiometry, subject to the aforementioned cost and thermodynamic constraints. In order to estimate the impact we assume 5% loss of reactor effluent by unavoidable leakage. We measure the impact in terms of the critical water mass (CTWM, Pistikopoulos et al., 1994). We solve the problem to determine the equilibrium composition and reaction temperature which correspond to the minimum environmental impact for each stoichiometry. The thermodynamic and environmental properties we require are calculated from group contributions (Van Krevelen et al., 1951; Gao et al., 1992). Finally we rank our stoichiometries according to economics and environmental impact in order to identify the most promising candidates. The mathematical details of our approach are reported elsewhere (Buxton et al., 1996).
+
COCI~
~
~
O--H
+ _
C
It O
~
"t-
HCI
O--C ~CI II O 1-Naphthalenyl Chloroformate
CI
CH3Nll:2
~
H l
O _ C ~ N~CH3 fl O Carlmryl
Figure 2: Non-Methyl Isocyanate Route We make our group pre-selection according to our New Rules for Co-Material Design (see Co-Material Design), restricting ourselves to the simplest set of groups which represent these molecules and the functional groups of interest. Employing the functional group definitions of Gani et al. (1991), our set of selected groups (12 in all) is then: (i) aromatic groups AC-, ACH, ACC1, ACOH; (ii) other groups °CH3, CH3NH<, C H 3 N H 2 - , - C O O - , - C H O , - C O 2 H , - O H , -C1.
Co-Material Design
We construct our co-material molecules according to Gani's molecular design procedure, (Gani et al., 1991) EXAMPLE PROBLEM PRODUCTION incorporating our new rules. Specifically, we introOF 1-NAPHTI-IALENYL METHYL duce the following structural and chemistry-based reCARBAMATE strictions: (i) we impose upper limits on the numProduct Identification bers of groups in our non-aromatic molecules so that 1-naphthalenyl methyl carbamate, also known as 'car- we retain the simplest set of non-aromatic molecules baryl' was employed as a pesticide (Worthy, 1985). It which contain functional groups of interest, (ii) we was manufactured under the trade name SEVIN by impose an upper limit of 14 groups within our aroUnion Carbide India, Limited (UCIL) in Bhopal un- matic molecules since it is unlikely that we would til December, 1984 when production was terminated synthesise our product from a more complex molecule -
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(earbarvl contains 14 groups), (iii) we allow only monosubstituted aromatic molecules (since the product is monosubstituted), (iv) we eliminate all molecules of which the carbon skeleton must be altered in order to achieve the product (e.g. we reject all benzyl (single ring) structures since we do not wish to be concerned with contructing the naphthyl (double ring) group). By applying these criteria we reduce our set of molecules to fifteen in total (see Figures 3 and 4).
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in any feasible stoichiometry. Thirteen stoichiometries meet this constraint, these routes are shown in Table 1, ranked according to their economic potential. The original Union Carbide industrial chemistry and one of the routes generated by Crabtree and E1Halwagi (1994) were reproduced, the other two routes put forward by Crabtree and E1-Halwagi were eliminated by our cost constraint.
&o-Material Design Results :~
CI a)
OH
b)
H~N~cH3 d)
c)
_ C ~ OH n O
O_c~CI II O 13
e)
~ ~. ~ ~ t.- ~. ~ ~. ~ .~ ~ e~ "~
O--C ~ ~CH 3 II O g)
Figure 3: Aromatic Molecules a) Naphthalene, b) 1-Chloronaphthalene c) 1-Naphthol, d) N-Methyl-l-Naphthylamine e) 1-Naphthalenyl Hydroxyformate f) 1-Naphthalenyl Chloroformate g) Carbaryl
CI2
CH3C |
CH3OH
CI--C~ H
H
a)
b)
c)
d)
H-- C ~ N ~ CH 3 II
CH3NH2
CI~C_. O CI
e)
CH3-- N = C = O
f)
,.7
,
"7"7"7"7
"77
"7,
7
"7,
O
h)
g)
Figure 4: Aliphatic and Other Molecules a) Chlorine, b) Methyl Chloride, c) Methanol d) Chloromethanal, e) Methylamine, f) Phosgene g) Methyl Isocyanate, h) Methyl Formamide
1 2 3 4
The isocyanate group and phosgene do not appear in Gani's method, so we add methyl isocyanate and phosgene to class zero (complete molecules).
5
Additional Molecules We introduce four additional co-material molecules: a) H 2 0
b) 02
c) H2
d) HC1
a) water b) oxygen c) hydrogen d) hydrogen chloride
6 7
8 9 10
Oxygen Hydrogen Hydrogen Chloride 1-Naphthol Chloroformate Methyl Formamide Water Methylamine Phosgene Methyl Isocyanate 1-Naphthol
11 12 13 14 15 16 17 18 19
Carbaryl Naphthalene 1-Chloronaphthalene N-methyl-l-Naphthyl Amine 1-Naphthalenyl Hydroxyformate Chlorine Chloromethane Methanol Chloromethanal
Table 1: Stoichiometry Selection Results
All of the alternative stoichiometries exhibit more promising economics than the Bhopal chemistry and more than half also exhibit lower environmental imStoichiometry Selection Results pact. Stoichiometries 5,6 and 12 represent the best The solutions from the stoichiometry selection pro- compromise solutions, with both promising economics grams are presented below in the form of a table of and low environmental impact. stoichiometric coefficients; blank spaces indicate zero Stoichiometries involving methyl isocyante (specie 9) coefficients. A basis production rate of 1 mol/hr of and/or 1-chloronaphthalene (specie 13) as raw macarbaryl was employed. An upper limit of six was im- terials exhibit relatively high environmental impact, posed on the number of molecules Nmot to be involved and should therefore be avoided.
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$964 APPENDIX
This work has employed the following assumptions (i) we assume that the Gibbs free energies of formation and of reaction are linear with temperature, (ii) we assume that the group contribution techniques we have used to obtain the Gibbs free energies of formation and toxicities of our molecules are suitable for all of our molecule (iii) we assume 5% of reactor effluent flow by mass is released by unavoidable leakage, (iv) we assume that all emissions are to the water phase, we do not model pollutant fate (v) we do not consider wastes which do not arise directly from the process chemistry (e.g. solvents and wash water), (vi) all generated molecules are chemically feasible, (vii) group based raw material design provides all interesting co-materials, (viii) we have applied limits to the numbers of groups to be allowed in any co-material and the number of functionalities, (ix) the additional molecules we require to complete our stoichiometries are not systematically designed or selected, (x) we apply an upper limit to the number of molecules which may be involved in any stoichiometry, (xi) side reactions are excluded by integer cuts, (xii) do not consider competing reactions at this stage, (xii) we assume low pressure (1 atm) gas phase reaction and we make the perfect gas assumption, (xiii) we employ a hierarchical screening procedure: economics, thermodynamics, then environmental impact, (xiv) we cost only the products and the reactants, no process equipment or operating costs (xv) we do not consider solvents, catalysts or reagents. Current research efforts are aimed at relaxing some of these assumptions.
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Douglas. J. M. (c1994). Process Alternatives for Pollution Prevention. Communication. University of Massachusetts. Fornari, T. and G. Stephanopoulos (1994). Synthesis of Chemical Reaction Paths: Economic and Specification Constraints. Chemical Engineering Communications 129, 159-182. Gani, R., B. Neilsen and A. Fredenslund (1991). A Group Contribution Approach to Computer Aided Molecular Design. AIChE Jounal 37(9), 1318-1332. Gao, C., R. Govind and H.H. Tabak (1992). Application of the Group Contribution Method for Predicting the Toxicity of Organic Chemicals. Environmental Toxicology and Chemistry 11,631-636. Govind, R. and G.J. Powers (1981). Studies in Reaction Path Synthesis. AIChE Journal 27(3), 429-442. Knight, J.P. (1995). Computer-Aided Tools to Link Chemistry and Design in Process Development. PhD Thesis, Massachusetts Institute of Technology. Linninger, A.A., Shahin A. Ali, E. Stephanopoulos, C. Hun and George Stephanopoulos (1995). Synthesis and Assessment of Batch Processes for Pollution Prevention. FOCAPD, AIChE Symposium Series 91, 41-51. Mavrovouniotis, M.L. and D. Bonvin (1995). Design of Reaction Paths. FOCAPD, AIChE Symposium Series 91, 41-51. Pistikopoulos, E. N., S. K. Stefanis and A. G. Livingston (1994). A Methodology for Minimum Environmental Impact Analysis. AIChE Symposium Series 90(303), 139-151. Rotstein, E., D. Resasco and G. Stephanopoulos (1982). Studies on the Synthesis of Chemical Reaction Paths - I. Chemical Engineering Science 37(9), 1337-1352. Ugi, I. and P. Gillespie (1971). Chemistry and Logical Structure. 3. Representation of Chemical Systems and Interconversions by BE matrices and their Transformation Properties. Agnew.Chem.Ind.Ed. Engl 10, 914. Van Krevelen, D.W. and H.A.G. Chermin (1951). Estimation of the free enthalpy (Gibbs free energy) of formation of organic compounds from group contributions. Chemical Engineering Science 1, 66-80. Worthy, W. (1985). Methyl Isocyanate: The Chemistry of a Hazard. Chemical and Engineering News 63(6), 27-33.