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Research Article

pubs.acs.org/journal/ascecg

Complete Green Metrics Evaluation of Various Routes to Methyl


Methacrylate According to Material and Energy Consumptions and
Environmental and Safety Impacts: Test Case from the Chemical
Industry
John Andraos*
CareerChem, 504-1129 Don Mills Road, Toronto, ON M3B 2W4, Canada
*
S Supporting Information

ABSTRACT: In this paper we present a standardized protocol for the


complete evaluation of greenness of 18 industrial routes to methyl
methacrylate (MMA) covering material and energy consumptions and
environmental and safety impacts. A methodology for estimating energy
consumption for chemical reactions and synthesis plans from published
journal and patent literature procedures is fully described. A new energy
metric pertaining to enthalpic changes from standard state conditions (298
K, 1 atm) to reaction conditions (Trxn, prxn) for all input materials used in a
synthesis plan for the production of 1 mol of product is defined with respect
to the heating and evaporation of 1 mol of water from 298 K and 1 atm.
Limitations and best practices of running the protocol are discussed. The
present study serves as a template for implementing the protocol to the
green metrics analysis of high volume industrial chemicals. Results of plan
rankings are compared with previous work on inherent safety indexes. Based on these findings, the isobutylene and t-butyl
alcohol routes to MMA are found to have the overall greenest attributes among the 18 routes examined.
KEYWORDS: Green metrics, Methyl methacrylate, Energy consumption, High volume production, Industrial chemistry

■ INTRODUCTION
Various methodologies for carrying out integrated green
rigorous and fraught with uncertainty. Most notably, para-
metrizations of cancer risk potential and endocrine disruption
metrics analyses of chemical reactions and synthesis plans are not yet fully understood. Despite these shortcomings, there
according to material efficiency have evolved over the past is general consensus that combined metrics analyses of well-
decade and are now firmly established.1−9 The key materials defined material consumption and albeit approximate environ-
efficiency metrics accepted by the chemical industry, most mental/safety impact give a more balanced and fair assessment
notably the pharmaceutical industry, are reaction yield (RY), of reaction or synthesis plan greenness for a given target
atom economy (AE),10 reaction mass efficiency (RME),11−13 compound than analyses based on material consumption alone.
E-factor (E),14 and process mass intensity (PMI).15,16 In 2009 However, trade-offs between them are often exposed which
we demonstrated the use of our own algorithm using these five leads to more difficult decision making with respect to declaring
metrics to ascertain the best synthetic route to oseltamivir which synthetic route is the most green among a set of
phosphate,17−19 a neuraminidase inhibitor of H5N1 influenza candidate plans. Up to now the question of energy
virus, from various published industrial and academic synthesis consumption has been given very little attention22 mainly
plans. Recently, we have endeavored to incorporate environ- because it is customary to not report these data in standard
mental and safety impact metrics in a simplified life cycle write ups of experimental procedures. However, inferences
assessment (LCA), thereby increasing the breadth and depth of about energy consumption can be made based on examination
our metrics analysis.20 These additional metrics cover standard of reaction conditions, namely, temperature and pressure, and
parameters associated with transport of chemicals in the of purification operations such as evaporation of solvents and
environment, human toxicity, bioaccumulation, and climate distillation of product. It should be pointed out that such
damage including octanol−water partition coefficients, Henry’s inferences rely only on thermodynamic considerations and do
law constants, LD50 and LC50 toxicity parameters, acid- not account for the actual electricity consumption of
ification, and global warming risk potentials among others.21 apparatuses used in all unit operations. In addition,
Unlike material consumption, agreement on which environ-
mental impact and health and safety metrics to choose has been Received: October 6, 2015
hampered due to ongoing issues related to unavailability and Revised: November 13, 2015
unreliability of necessary data, thus making analyses less

© XXXX American Chemical Society A DOI: 10.1021/acssuschemeng.5b01240


ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Scheme 1. Eighteen Industrial Routes to Methyl Methacrylate

B DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Scheme 1. continued

C DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Scheme 1. continued

Figure 1. Flowchart showing the steps followed in carrying out thermodynamic computations for input materials in a synthesis plan.

D DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

experimental details for high volume industrial chemicals that the Supporting Information). Using appropriate thermodynamic data,
are the first, second, and third generation feedstocks to the the molar enthalpic changes due to temperature and pressure
chemical industry are well-known and well documented in the contributions for each input substance are determined according to
literature. Therefore, a set of synthetic routes to any one of eq 2.30 An Excel spreadsheet is given in the Supporting Information
(materials-thermodynamic-parameters.xls) summarizing thermody-
these feedstock chemicals from fossil fuel starting materials can namic data for all input materials used for the 18 synthetic routes to
serve as a good template to test a proposed method for MMA.
estimating energy consumption. In this work we have chosen
methyl methacrylate (MMA) as the test target compound for ΔH = qtemp + qpress
our present study on estimating energy consumption metrics ⎡
T2 p2 ⎛ ⎞ ⎤
since it has been reviewed previously and a variety of industrial = ∫T C p(T ) dT + ∫p ⎢V − T ⎜ ∂V ⎟ ⎥ dp
routes are well-described.23−27 Scheme 1 shows 18 routes to ⎢⎣ ⎝ ∂T ⎠ p⎥⎦
1 1 (2)
MMA examined that were extracted from a reaction network
published by Nagai24 (see Scheme S1 in Part 1 of the where ΔH = H2 − H1 is the enthalpy change in kilojoules per mole
Supporting Information). Each chemical equation is fully between the standard state (298 K, 1 atm) and the reaction state (Trxn,
prxn), Cp (T) is a temperature dependent heat capacity function at
balanced and the key reaction conditions of temperature and
constant pressure pertaining to the phase of the substance, T1 = 298 K,
pressure for each step are shown. A complete list of references T2 = Trxn, p1 = 1 atm, p2 = prxn, and V is the molar volume (L/mol).
for these routes is given in Part 2 of the Supporting Temperature Contribution. For each input material in a plan the
Information. To facilitate comparison with prior published enthalpy change in kilojoules for heating that substance from 298 K to
work on this compound, we have preserved the specialized the reaction temperature is determined on a per mole basis and is
designations attached to the first 8 routes: routes 1a and 1b given by the parameter q. Processes involving heating have q > 0 and
(ACHacetone cyanohydrin), route 2 (C2/PAethylene those involving cooling have q < 0. The q value of a given substance is
based via propionaldehyde), route 3 (C3propylene based via then multiplied by its corresponding mole scale as prescribed in the
isobutyric acid), route 4 (C2/MPethylene based via methyl synthesis plan in which that substance appears. The procedure is
repeated for all input materials in a plan and the overall input energy
propionate), route 5 (iC4isobutylene based), route 6
sum is determined for a 1 ton synthesis of MMA which can then be
(TBAtertiary butyl alcohol based), route 7 (PApropyl converted back to units of kilojoules per mole. The enthalpic
alcohol based), and route 8 (PPpropylene based via contribution due to heating a substance depends on the phase
isopropyl chloride).


transitions it can undergo from standard state conditions (298 K and 1
atm) to reaction conditions. The following cases given by eqs 3−11
METHODOLOGY illustrate the possible calculation scenarios for determining the
(1) Material Consumption. For each route shown in Scheme 1, temperature change contribution to enthalpy. All thermodynamic
the global AE, yield, RME, and PMI parameters were determined at a data were obtained from the DIPPR (Design Institute for Physical
common basis scale of 1 ton of methyl methacrylate using the recently Property Data) database31 and Yaws.32
updated REACTION and SYNTHESIS Excel spreadsheet algorithm.28 Case I. Heating a liquid at 298 K from 298 K to Trxn (Trxn is above
(ii) Environmental and Safety Impact. For each route shown in boiling point, Tb) where the liquid undergoes a phase transition from
Scheme 1, the benign index for waste materials, (BI)w, safety-hazard liquid to gas:
index for waste materials, (SHI)w, and safety-hazard index for input Tb Trxn
materials, (SHI)in, were determined according to our previously q= ∫298 Cp,liq(T ) dT + ∫T C p,gas(T ) dT + ΔH vap
(3)
reported algorithm.20 The Supporting Information contains a b

summary Excel spreadsheet summarizing all environmental and safety


impact parameters for all input materials used in the 18 synthetic C p,liq(T ) = A + BT + CT 2 + DT 3 + ET 4 (4)
routes to MMA (environmental-safety-analysis-MMA.xls, missing-
data.xls). ⎡ C / T ⎤2 ⎡ E / T ⎤2
(iii) Route Ranking Based on Materials and Environmental/ C p,gas(T ) = A + B⎢ ⎥ + D⎢ ⎥
⎣ sinh(C /T ) ⎦ ⎣ cosh(E /T ) ⎦ (5)
Safety Impact. The 18 routes were ranked according to the vector
magnitude ratio (VMR)29 parameter covering AE, yield, RME, (BI)w, where ΔHvap is the heat of vaporization, the functions Cp(T) represent
(SHI)in, and (SHI)w metrics as given by eq 1. the temperature dependent heat capacity functions at constant
1 pressure for liquids and gases, and the parameters A, B, C, D, and E
VMR = [(AE)2 + (RY)2 + (RME)2 + (BI w )2 + (SHI w )2 are constants specific to a given substance.
6
Case II. Heating a liquid at 298 K from 298 K to Trxn (Trxn is below
+ (SHI in)2 ]1/2 (1) boiling point, Tb) where the liquid does not undergo a phase
transition:
(iv) Energy Consumption. Based on temperature and pressure
Trxn
conditions reported for each reaction step, the total input energy
required to heat, cool, and pressurize all input materials in a synthesis
q= ∫298 C p,liq(T ) dT
(6)
plan at the appropriate reaction conditions were determined. In this
treatment the energy consumption to operate all necessary equipment Case III. Heating a gas at 298 K from 298 K to Trxn:
including their intrinsic efficiencies were neglected. Hence, the Trxn
calculated results presented should be considered theoretical minimum q= ∫298 C p,gas(T ) dT
(7)
estimates for actual input energy consumption.
Figure 1 shows a flowchart of steps followed for carrying out Case IV. Heating a solid at 298 K from 298 K to Trxn (Trxn is above
thermodynamic calculations. A basis scale of 1 ton for MMA is set for both the boiling point, Tb, and the melting point, Tm) where the solid
all plans and the corresponding mole scales and masses of all input undergoes phase transitions from solid to liquid and from liquid to gas:
materials required in a given synthesis plan to produce a final mass of 1 Tm Tb Trxn
ton of MMA are determined. The phases of each input material at 298 q= ∫298 Cp,sol(T ) dT + ∫T C p,liq(T ) dT + ∫T C p,gas(T ) dT
K and 1 atm (state 1) and at Trxn and prxn (state 2) are determined m b
according to a set of inequality conditions based on reduced
+ ΔHfus + ΔH vap (8)
temperature and reduced pressure values (See Figure S1 in Part 3 of

E DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

C p,sol(T ) = A + BT + CT 2 + DT 3 + ET 4 (9) ⎡ RT b a ⎛ 1 ⎞ 3a ⎛V + b ⎞⎤
q=⎢ 2
− ⎜ ⎟− ln⎜ 2 ⎟⎥
where ΔHfus is the heat of fusion and Cp,sol (T) is the temperature ⎢⎣ V2 − b T2 ⎝ V2 + b ⎠ 2b T2 ⎝ V2 ⎠⎥⎦
dependent heat capacity function at constant pressure for solids. ⎡ RT b a ⎛ 1 ⎞ 3a ⎛V + b ⎞⎤
Case V. Heating a solid at 298 K from 298 K to Trxn (Trxn is above −⎢ b
− ⎜ ⎟− ln⎜ 1 ⎟⎥
melting point, Tm) where the solid undergoes a phase transition from ⎢⎣ V1 − b Tb ⎝ V1 + b ⎠ 2b Tb ⎝ V1 ⎠⎦⎥ (15)
solid to liquid:
where the Redlich−Kwong equation of state (RKEOS) for gases is
Tm Trxn
used, a and b are the attraction and repulsion constants, and V1 and V2
q= ∫298 C p,sol(T ) dT + ∫Tm
C p,liq(T ) dT + ΔHfus
(10) are the respective molar volumes (L/mol). The units of q are liters
atmospheres per mole which can be converted to kilojoules per mole
Case VI. Heating a solid at 298 K from 298 K to Trxn (Trxn is below by multiplying by 0.101 325.
melting point, Tm) where the solid does not undergo a phase Case III. Transition from state 1 (liquid at 298 K and 1 atm =
transition: 101 325 Pa) to state 2 (liquid at T2 and p2):
Trxn
q= ∫298 C p,sol(T ) dT ⎧

(11) q = (1 − ϕT2)Vs⎨(p2 − 101325)(1 + C)

The overall input energy temperature contribution for N input ⎩
substances in a synthesis plan is given by eq 12. ⎡ ⎛B + p ⎞
⎛ B + p2 ⎞
N − BC ln⎜ ⎟ − C ⎢p2 ln⎜⎜ 2⎟

⎝ B + 101325 ⎠ ⎢⎣ ⎝ B + ps ⎠
Q temp = ∑ qj ,tempxj
j=1 (12) ⎛ B + 101325 ⎞⎤⎪⎫
where xj is the number of moles of substance j and qj,temp is the heat − 101325ln⎜⎜ ⎟⎟⎥⎬
input in kiloloules per mole given by any one of the expressions shown ⎝ B + ps ⎠⎥⎦⎪ ⎭ (16)
in eqs 3−11. Since all xj mole scales are referenced to production of 1
ton of MMA, the units for overall Qtemp from eq 12 are kilojoules per where the Tait equation of state for liquids was used, ϕ is the thermal
ton MMA which can then be converted to kilojoules per mole MMA. expansion coefficient equal to (1/V)(∂V/∂T)p (1/K) evaluated at the
Pressure Contribution. Enthalpic contributions due to changing reaction temperature T2,32 Vs is the molar volume (L/mol) at reaction
pressure were determined by applying the Redlich−Kwong equation temperature T2 and 1 atm = 101 325 Pa, ps is the vapor pressure (Pa)
of state (RKEOS) function to gases33 or the Tait equation to at reaction temperature T2, and the constants B and C are given by eqs
liquids34,35 depending on the phase of the input material at the 17 and 18.34 The units of q from eq 16 are pascals liters per mole
reaction conditions. In engineering thermodynamics textbooks, which can be converted to kilojoules per mole by dividing by 106.
calculations of enthalpy changes often neglect the pressure B
contribution (second term in eq 2) if reaction pressures are less = − 1 + a(1 − Tr)1/3 + b(1 − Tr)2/3 + d(1 − Tr)
than 100 atm.30,36 However, in our present investigation, we were pc
required to take this term into account for the following cases: route 4 + e(1 − Tr)4/3 (17)
(step 1, p = 745 atm), route 8 (step 2, p = 400 atm), route 11 (step 1,
p = 780 atm), route 12 (step 3, p = 145 atm), route 16 (step 1, p = C = 0.0861488 + 0.0344483ω (18)
780), route 17 (step 1, p = 500 atm), and route 18 (step 1, p = 500
atm). Since such calculations are rarely described, we decided to where pc is the critical pressure (Pa), Tr is the reduced temperature
implement them for any reaction we encountered that was conducted equal to T/Tc, Tc is the critical temperature (K), ω is the acentric
at pressures exceeding 1 atm. Illustrative examples of such calculations factor, a = −9.070 217, b = 62.453 26, d = −135.1102, e = exp[f + gω +
for substances that are gases or liquids at elevated pressures are given hω2], f = 4.795 94, g = 0.250 047, and h = 1.141 88. Alternatively, eq
in part 7 of the Supporting Information. The pressure contribution to 19 may be used to approximate q if it is assumed that the molar
the overall input energy for N input substances in a synthesis plan is volume of the liquid does not change with pressure over the range
given by eq 13. 101 325 Pa to p2 Pa.
N
q = (1 − ϕT2)Vs(p2 − 101325) (19)
Q press = ∑ qj ,pressxj
j=1 (13) Case IV. Transition from state 1 (gas at 298 K and 1 atm) to state 2
(liquid at T2 and p2) via the intermediate gaseous state at T2 and
where xj is the number of moles of substance j and qj,press is given by
saturation pressure, psat:
eqs 14−21 depending on the phase transition from state 1 to state 2.
Case I. Transition from state 1 (gas at 298 K and 1 atm) to state 2 ⎡ RT b a ⎛ 1 ⎞ 3a ⎛V + b ⎞⎤
(gas at T2 and p2): q=⎢ 2
− ⎜ ⎟− ln⎜ sat ⎟⎥
⎢⎣ Vsat − b T2 ⎝ Vsat + b ⎠ 2b T2 ⎝ Vsat ⎠⎦⎥
⎡ RT b a ⎛ 1 ⎞ 3a ⎛V + b ⎞⎤
q=⎢ 2
− ⎜ ⎟− ln⎜ 2 ⎟⎥ ⎡ RTb a ⎛ 1 ⎞ 3a ⎛V + b ⎞⎤
⎢⎣ V2 − b T2 ⎝ V2 + b ⎠ 2b T2 ⎝ V2 ⎠⎦⎥ −⎢ 1
− ⎜ ⎟− ln⎜ 1 ⎟⎥
⎢⎣ V1 − b T1 ⎝ V1 + b ⎠ 2b T1 ⎝ V1 ⎠⎦⎥
⎡ RTb a ⎛ 1 ⎞ 3a ⎛ V + b ⎞⎤
−⎢ 1
− ⎜ ⎟− ln⎜ 1 ⎟⎥ ⎧
⎪ ⎛B+p ⎞
⎢⎣ V1 − b T1 ⎝ V1 + b ⎠ 2b T1 ⎝ V1 ⎠⎦⎥ (14) + (1 − ϕT2)Vs⎨(p2 − psat )(1 + C) − BC ln⎜⎜ 2 ⎟
⎪ ⎟
⎩ ⎝ B + psat ⎠
where the Redlich−Kwong equation of state (RKEOS) for gases is
used, a and b are the attraction and repulsion constants, T1 = 298 K, ⎡ ⎛B + p ⎞ ⎛ B + p ⎞⎤⎫ ⎪
and V1 and V2 are the respective molar volumes (L/mol). The units of − C ⎢p2 ln⎜⎜ 2⎟
⎟ − psat ln⎜⎜ sat ⎟⎥
⎟⎥⎬
q are liters atmospheres per mole which can be converted to kilojoules ⎢⎣ ⎝ B + ps ⎠ ⎝ B + ps ⎠⎦⎭

(20)
per mole by multiplying by 0.101 325.
Case II. Transition from state 1 (liquid at 298 K and 1 atm) to state where the Redlich−Kwong equation of state (RKEOS) for gases and
2 (gas at T2 and p2) via the intermediate liquid state at the boiling the Tait equation of state for liquids are used, T1 = 298 K, a and b are
point, Tb, and 1 atm): the attraction and repulsion constants, and V1 and Vsat are the

F DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Table 1. Summary of Global Material Efficiency Metrics for MMA Syntheses According to Scheme 1
plan number of stepsa RY (%) AE (%) E RME (%) PMI rank
route 1a (ACH) 3, L 57.4 37.2 6.90 12.7 7.90 2
route 1b (ACH) 5, C 46.2 34.8 7.97 11.1 8.97 3
route 2 (C2/PA) 4, L 55.6 73.5 15.52 6.1 16.52 7
route 3 (C3) 3, L 26.8 42.7 18.00 5.3 19.00 9
route 4 (C2/MP) 3, C 72.2 50.0 10.30 8.8 11.30 4
route 5 (iC4) 3, L 65.7 73.5 29.60 3.3 30.60 13
route 6 (TBA) 3, L 64.9 64.9 29.66 3.3 30.66 14
route 7 (PA) 3, L 30.2 39.7 15.70 6.0 16.70 8
route 8 (PP) 3, L 40.6 57.3 856.40 0.1 857.40 20
route 9 2, L 64.2 42.7 14.28 6.5 15.28 5
route 10 3, L 56.9 46.7 5.19 16.2 6.19 1
route 11 4, L 25.4 46.3 25.40 3.8 26.40 12
route 12 3, L 17.5 58.1 89.86 1.1 90.86 17
route 13a 5, L 44.0 52.9 21.54 4.4 22.54 10
route 13b 7, C 35.4 48.3 15.23 6.2 16.23 6
route 14 2, L 3.7 64.9 63.12 1.6 64.12 16
route 15 3, L 62.6 51.0 38.63 2.5 39.63 15
route 16 4, L 27.9 50.5 92.40 1.1 93.40 18
route 17 4, L 12.2 40.0 24.88 3.9 25.88 11
route 18 3, L 18.1 73.5 310.03 0.3 311.03 19
a
L = linear; C = convergent.

respective molar volumes (L/mol). By analogy with eq 19 for case III, of synthesis plans based on this parameter are more comprehensive
q may be approximated by eq 21. and should be more reliable than those determined from eq 1.
⎡ RT b
q=⎢ 2
⎢⎣ Vsat − b

a ⎛ 1 ⎞
⎜ ⎟−
T2 ⎝ Vsat + b ⎠
3a ⎛V +
ln⎜ sat
2b T2 ⎝ Vsat
b ⎞⎤
⎟⎥
⎠⎦⎥
■ RESULTS AND DISCUSSION
Material Efficiency. Table 1 summarizes the essential
⎡ RTb a ⎛ 1 ⎞ 3a ⎛ V + b ⎞⎤ material efficiency metrics for the 18 routes to MMA. Rankings
−⎢ 1
− ⎜ ⎟− ln⎜ 1 ⎟⎥
⎢⎣ V1 − b T1 ⎝ V1 + b ⎠ 2b T1 ⎝ V1 ⎠⎦⎥
Table 2. Global E-Factor Breakdown for MMA Syntheses
+ (1 − ϕT2)Vs(p2 − psat ) (21) According to Scheme 1
Full derivations of eqs 14−21 including corresponding state-to-state plan E-aux E-byproducts E-unreacted E-total
path diagrams following the method of Tosun37 are given in Parts 6 route 1a (ACH) 0.75 4.30 1.86 6.90
and 8 of the Supporting Information. Again, the units for overall Qpress route 1b (ACH) 0.77 5.11 2.09 7.97
from eq 13 are kilojoules per ton MMA which can then be converted route 2 (C2/PA) 10.50 4.61 0.41 15.52
to kiljoules per mole MMA. In all cases the magnitude of the route 3 (C3) 1.22 2.37 14.41 18.00
temperature change contribution to ΔH in eq 2 far exceeded that of
route 4 (C2/MP) 1.25 1.12 7.93 10.30
the pressure change contribution; i.e., Qtemp ≫ Qpress.
(v) Route Ranking Based on Materials, Environmental/ route 5 (iC4) 27.21 0.64 1.75 29.60
Safety Impact, and Energy Consumption. The 18 routes were route 6 (TBA) 27.21 0.64 1.81 29.66
ranked according to the vector magnitude ratio (VMR)29 parameter route 7 (PA) 1.17 2.37 12.16 15.70
covering AE, yield, RME, (BI)w, (SHI)in, (SHI)w, and (EI)in metrics as route 8 (PP) 769.20 1.82 85.06 856.09
given by eq 22. route 9 10.28 1.83 2.17 14.28
1 route 10 1.21 1.54 2.44 5.19
VMR = [(AE)2 + (RY)2 + (RME)2 + (BI w )2 + (SHI w )2 route 11 8.92 1.60 14.88 25.40
7
route 12 69.85 3.40 16.62 89.86
+ (SHI in)2 + (EI in)2 ]1/2 (22) route 13a 4.12 2.38 15.04 21.54
where an energy index for input materials is defined as shown in eq 23. route 13b 3.05 1.62 10.56 15.23
route 14 26.26 0.57 36.28 63.12
⎧1, Q plan ≤ 2qwater = 92.62 route 15 29.93 1.03 7.68 38.63


EI in = ⎨ q route 16 50.44 1.18 40.78 92.40
water
⎪ , Q plan > 2qwater = 92.62 route 17 1.01 2.69 21.17 24.88
⎪ Q plan − q
⎩ water (23) route 18 303.06 0.38 6.60 310.03

The overall input energy consumption Qplan = Qtemp + Qpress in units of


kilojoules per mole MMA for a synthesis plan is compared to the based on PMI values are given in the last column. From these
energy input required to heat and evaporate 1 mol of liquid water from
a starting state of 25 °C and 1 atm (46.31 kJ/mol). Note that the input data we observe that the most material efficient plan having the
energy index is defined as a value ranging between 0 and 1, consistent least PMI is route 10 involving nickel catalyzed multi-
with the other metrics contributing to VMR. Since the VMR component assembly of ethylene, carbon monoxide and water
determined from eq 22 covers material efficiency, environmental to give propanoic acid, followed by esterification to methyl
impact, safety/hazard impact, and input energy consumption, rankings propionate, and final condensation with formaldehyde to give
G DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Table 3. Summary of BI(waste), SHI(waste), and SHI(input) Closer examination of the E-factor breakdown contributions
Indices and Uncertainty Estimates for MMA Syntheses from auxiliary material consumption, reaction byproducts, and
According to Scheme 1a unreacted starting materials as shown in Table 2 indicates that
routes 1a/b (ACH), 3 (C3), 4 (C2/MP), 7 (PA), 10
plan (BI)w (SHI) w (SHI)in
(propanoic acid), and 17 (hydroformylation-oxidation/dehy-
route 1a (ACH) 0.987; 4% 0.956; 5% 0.906; 5% drogenation-esterification) have the least E-aux; routes 5 (iC4),
route 1b (ACH) 0.989; 3% 0.995; 5% 0.989; 5% 6 (TBA), 14 (isobutane oxidation/dehydogenation-esterifica-
route 2 (C2/PA) 0.982; 3% 0.994; 8% 0.978; 8% tion), and 18 (hydroformylation-oxidation/dehydrogenation-
route 3 (C3) 0.912; 2% 0.973; 6% 0.977; 7%
esterification) have the least E-byproducts; and route 2 has the
route 4 (C2/MP) 0.977; 3% 0.963; 9% 0.968; 9%
least E-unreacted starting materials. Route 10 with the lowest
route 5 (iC4) 0.995; 3% 0.988; 10% 0.986; 11%
overall PMI has low values for each of these E-factor
route 6 (TBA) 0.995; 2% 0.988; 10% 0.986; 11%
contributions across the board.
route 7 (PA) 0.906; 3% 0.979; 6% 0.981; 7%
Inclusion of Environmental-Safety/Hazard Impacts.
route 8 (PP) 0.995; 2% 0.999; 4% 0.997; 4%
Table 3 summarizes the BI and SHI indices, including
route 9 0.975; 8% 0.851; 10% 0.825; 9%
uncertainties expressed as a percentage of missing data
route 10 0.960; 5% 0.849; 4% 0.917; 1%
parameters, for all 18 MMA routes. From these data we
route 11 0.977; 6% 0.984; 7% 0.989; 6%
observe that the routes producing the most benign waste with
route 12 0.993; 5% 0.984; 8% 0.975; 9%
route 13a 0.996; 6% 0.994; 8% 0.993; 10%
respect to environmental impact are routes 5, 6, 8, and 13a/b.
route 13b 0.995; 5% 0.995; 7% 0.994; 8%
Routes 1a/b arising from ingestion toxicity due to unreacted
route 14 0.989; 4% 0.990; 7% 0.989; 9%
acetone cyanohydrin, route 4 arising from ingestion toxicity due
route 15 0.983; 4% 0.944; 6% 0.951; 7%
to potassium cyanide, and routes 3 and 7 arising from
route 16 0.982; 4% 0.991; 9% 0.976; 10%
inhalation risks due to unreacted carbon monoxide substrate
route 17 0.958; 5% 0.996; 9% 0.996; 10% produce the most environmental harm. Routes 8, 13a/b, and 17
route 18 0.993; 5% 0.467; 9% 0.472; 10% produce the least hazardous wastes; whereas, routes 10 and 18
a produce the most hazardous waste due to occupational
Uncertainties are determined as the fraction of missing parameters
required to determine the indices.43 exposure risk from nickel tetracarbonyl and quartz dust
inhalation, respectively. The next ranking hazardous wastes
arise from routes 9, 15, and 18 which involve occupational
MMA. The next most material efficient route is the traditional exposure risks from benzene solvent, nickel tetracarbonyl
acetone cyanohydrin route (routes 1a and 1b). Route 4 (C2/ catalyst, and quartz dust inhalation, respectively. The same
MP) has the highest overall yield, and routes 2 (C2/PA), 5 routes are implicated with respect to least and most hazardous
(iC4), and 18 (hydroformylation-oxidation/dehydrogenation- input materials rankings. Environmental harm due to ingestion
esterification) have the highest atom economies at 73.5% each. and inhalation toxicities dominated the benign index

Figure 2. Radial polygon diagrams showing VMR scores according to eq 1 for the top six MMA plans in Scheme 1.

H DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Table 4. Summary of Energy Consumption Data for MMA sumption), the overall greenest routes according to their VMR
Syntheses Shown in Scheme 1 scores via eq 23 are routes 5 (iC4), 6 (TBA), and 2 (C2/PA) as
shown by the radial polygon diagrams given in Figure 4. A
energy energy consumption total energy
consumption to to pressurize input consumption, complete list of VMR scores is given in Table S1 and shown
heat input materials materials Qpress (kJ/ Qplan (kJ/mol graphically in Figure S2 in Parts 4 and 5 of the Supporting
Qtemp (kJ/mol mol MMA MMA Information. Our result that routes 5 and 6 are the greenest
plan MMA produced) produced) produced)a rank
routes among the 18 plans considered is consistent with the
route 1a 948 0.4 948 10
(ACH) Edwards−Lawrence inherent safety index (ISI) analysis based
route 1b 1124 0.5 1124 11 on simple chemical and process scores23 (see Table 5). The
(ACH) adjusted ISI scores presented here based on summing scores
route 2 502 −3 505 5 from all input materials in a given synthesis plan is more
(C2/PA) realistic than selective summing of only maximal values from
route 3 144 0.1 144 1 the most offending chemicals as was done by Edwards and
(C3)
route 4 1850 −67 1917 14
Lawrence. Though the Edwards−Lawrence analysis is based on
(C2/MP) an arbitrary penalty point scoring system with no mass
route 5 551 0.1 551 7 weighting of scores and a limited number of parameters, it is
(iC4) satisfying that our analysis based on direct use of a wide range
route 6 645 0.1 645 8 of parameter values without invoking assumptions is in good
(TBA)
route 7 228 −2 230 3
agreement for the top ranking plans. However, agreement in
(PA) the ranking of the rest of the nine routes listed in Table 5
route 8 377 −61 438 4 begins to break down (compare columns 4 and 7). This is
(PP) typical of all kinds of ranking schemes. The same best
route 9 147 −2 149 2 performing plans tend to rise to the top of the list and poor
route 10 698 −16 714 9 performing ones tend to end up at the bottom regardless of the
route 11 1476 66 1542 12 sophistication of the algorithms used to produce the ranking.
route 12 2782 5 2787 16 Our algorithm is able to differentiate all plans without having
route 13a 3185 1.2 3186 17 any ties unlike the ISI analysis which is unable to distinguish
Route 13b 1897 0.6 1898 13
routes 5/6 and 3/7 (adjusted ISI scores) and 5/6 and 3/8 (ISI
route 14 5768 0 5768 20
scores). ISI analysis predicts that routes 1b and 2 are the worst
route 15 1911 −41 1952 15
of the nine listed; whereas, our algorithm suggests that route 1b
route 16 3972 176 4148 18
ranks sixth out of 9, route 2 ranks third out of 9, and route 7
route 17 457 −67 524 6
ranks last. Table 6 compares rankings of routes 1a, 2, 5, and 6
route 18 4943 −111 5054 19
using a wider list of published methods that were applied to this
a
Total input energy consumption is given by Qplan = Qtemp + |Qpress|. limited set of plans.38−42 In this comparison there is generally
better agreement between best and worst plans. Again, routes 5
contributions for all plans; whereas, occupational exposure and 6 rank highest and route 1a ranks lowest among this
limits and skin dose risk potentials dominated the safety-hazard limited set of MMA synthesis plans. If we consider the first 8
index contributions. Figure 2 shows plans with the top six VMR plans in Scheme 1 as traditional routes to MMA, then among
scores that incorporate both material efficiency and environ- the remaining 10 alternative routes the next greenest routes
mental-safety/hazard risk potentials. The most material efficient that can compete with routes 5 and 6 are routes 13a/b (ACH-
route 10 is not among these. Instead, the most favorable routes hydration-dehydration), 14 (isobutane oxidation/dehydogena-
are in descending order 5 (iC4), 6 (TBA), 2 (C2/PA), 4 (C2/ tion-esterification), and 15 (propanoic acid-condensation-
MP), 8 (PP), and 13a (ACH-hydration-dehydration). esterification). The main drawbacks are the number of steps
Inclusion of Input Energy Consumption. Table 4 (routes 13a/b), a low yield of 4% for the isobutane oxidation
summarizes the energy input contributions from heating and and a high input energy demand (route 14), and toxicity issues
with nickel catalysts particularly nickel tetracarbonyl (route 15).


pressuring input materials for all 18 MMA syntheses calculated
as described in the Methodology section. Excel workbook
spreadsheets summarizing these calculations for all routes is CONCLUDING REMARKS
given in the Supporting Information (change in enthalpy- In this extensive metrics study of the test case of 18 industrial
pressure contribution-MMA.xls, energy-input-analysis- syntheses of MMA we conclude that the isobutylene and t-
MMA.xls). Routes 3 (C3), 9 (multicomponent coupling of butanol routes have the greenest attributes with respect to
propyne, methanol, and carbon monoxide), and 7 (PA) are the material efficiency, environmental and safety-hazard impacts,
top three least energy intensive routes; whereas, routes 16 and input energy consumption. The basis of this conclusion
(hydroformylation-oxidation-condensation-esterification), 14 relies on comparison and ranking of the normalized VMR
(isobutane oxidation/dehydogenation-esterification), and 18 parameter that encompasses the following seven variables:
(hydroformylation-oxidation/dehydrogenation-esterification) overall atom economy, overall reaction yield, global reaction
are the most energy demanding. From Figure 3 we observe that mass efficiency, (BI)w, (SHI)w, (SHI)in, and a newly defined
route 14 has the highest Qtemp contribution (step 1, T = 420 energy input index. Each of these variables varies in value
°C) and route 16 has the highest Qpress contribution (step 1, p = between 0 and 1 where unity corresponds to complete
780 atm) arising from compression of gaseous ethylene, carbon greenness within the limitations of variables selected in the
monoxide, hydrogen, and liquid diethyl ether. When all three present algorithm. The benign, safety-hazard, and energy input
layers of metrics are taken into account (material efficiency, indices are mass weighted to reflect the fractional contribution
environmental-safety/hazard risk potentials, and energy con- of each input or waste material to the total mass of inputs or
I DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Figure 3. Histogram showing temperature and pressure contributions to total energy input for production of 1 mol of MMA.

Figure 4. Radial polygon diagrams showing VMR scores according to eq 22 for the top six MMA plans in Scheme 1.

wastes produced in a synthesis plan. Accompanying un- synthesis plan to produce 1 mol of target product. The
certainties in the determination of the BI and SHI indices are methodology we have introduced relies only on the availability
also given. The energy input index uses the energy required to of necessary input data to determine the required metrics
evaporate 1 mol of water as a benchmark for comparing the variables and does not rely on any arbitrary merit or penalty
enthalpic energy consumption from all input materials in a point system unlike previously reported inherent safety index
J DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

Table 5. Summary of Edwards−Lawrence Inherent Safety heat integration possibilities and cooling duties in the analysis
Index (ISI) Analysis on MMA Syntheses23 may offset the present energy estimates in the opposite
direction. Another limitation of the present methodology for
adjusted overall rank from this
plan code ISIa rank ISIb rank work energy consumption is that it is limited to a given process
system boundary. The analysis could be expanded by including
route 1a ACH (a) 99 2 51 2 7
upstream energy demands for production of the input raw
route 1b ACH 143 5 80 6 6
(b) materials used in the synthesis pathways, particularly for high
route 2 C2/PA 146 6 63 4 3 production volume chemicals. However, there will always be
route 3 C3 106 3 53 3 8 the problem of how far back upstream one should go in the
route 4 C2/MP 160 7 68 5 4 synthesis network to begin such an extensive analysis. Any
route 5 iC4 86 1 39 1 1 change in where to start the energy consumption analysis also
route 6 TBA 86 1 39 1 2 impacts the analyses of material efficiency, environmental
route 7 PA 106 3 51 2 9 impact, and safety-hazard impacts, since all four analyses must
route 8 PP 119 4 53 3 5 start from the same set of input materials. Of course, direct
a
ISI calculated based on summing chemical and process scores for experimental measurement of actual energy consumption for
each input material used in synthesis plan. bISI calculated based on any given reaction is the most reliable method of estimating
summing only maximal chemical and process scores for each reaction total energy consumption and would supersede the present
step in synthesis plan. algorithm. Therefore, it behoves researchers to disclose such
determinations, along with a complete itemization of masses of
algorithms. In principle, the current set of parameters can be all materials used, if they claim that their process to a given a
expanded to include any number of potential risk variables target molecule is greener than prior published work.
provided data exist. Hence, the algorithm is versatile in adapting
to more complex analyses. In keeping with all of our past work
on metrics analysis, our latest version continues to use simple

*
ASSOCIATED CONTENT
S Supporting Information
visual diagrams, radial polygons, to highlight strengths and The Supporting Information is available free of charge on the
weaknesses of individual reaction and overall plan performance ACS Publications website at DOI: 10.1021/acssusche-
with a view to provide chemists and chemical engineers with a meng.5b01240.
useful tool in their ongoing efforts for process optimization. Part 1: Scheme S1. Reaction network for MMA. Part 2:
The method also produces reliable ranking of plans particularly Reference list for routes 1a to route 18 for the synthesis
with respect to differentiating ones that fall in between the of MMA. Part 3: Figure S1. Determination of phase of
extremes of best and worst performers. The only limitation in input materials in a given chemical reaction. Part 4: Table
implementing the present algorithm is the availability of reliable S1. Summary of overall VMR performances for 18 routes
environmental impact, safety-hazard impact, and thermody- to MMA. Part 5: Figure S2. Radial polygon diagrams
namic parameters. For first, second, and third generation showing VMR scores according to eq 22. Part 6:
feedstocks having simple chemical structures this will not be a Derivation of eqs 14−21. Part 7: Example calculations
problem due to readily available extensive compilations of using Redlich−Kwong equation of state and Tait
experimental data, and therefore it is expected to produce equation for pressure contribution to ΔH. Part 8:
reliable results. However, this will not be the case for complex Tosun equation for enthalpy change due to temperature
intermediates as found in advanced pharmaceuticals, partic- and pressure contributions for gases. Excel spreadsheet of
ularly with respect to obtaining experimental thermodynamic, environmental and safety impact data: environmental-
environmental, and toxicity data. Computational estimates of safety-analysis-MMA.xls, missing-data.xls. Excel spread-
thermodynamic parameters from chemical structures such as sheet of thermodynamic data: materials-thermodynamic-
critical constants, boiling points, melting points, and heat parameters.xls. Excel workbook spreadsheets of thermo-
capacities are possible to overcome any experimental gaps that dynamic calculations: change in enthalpy-pressure
arise and are described elsewhere.34,44 contribution-MMA.xls, change in enthalpy-pressure
With respect to estimating input energy consumption from contribution-template.xls, energy-input-analysis-
literature experimental procedures, the present investigation MMA.xls, Redlich-Kwong-EOS-template.xls (ZIP)


gives a rigorous protocol that uses fundamental thermodynamic
principles for determining energy contributions from heating,
cooling, and pressurizing operations. However, it must be AUTHOR INFORMATION
pointed out that such results are to be interpreted as lower limit Corresponding Author
estimates since actual electricity consumption and intrinsic *E-mail: c1000@careerchem.com.
efficiencies of apparatuses used in any unit operation are not Notes
taken into account. On the other hand, inclusion of process The authors declare no competing financial interest.

Table 6. Summary of Literature Ranking Comparisons for Four Common Routes to MMA

Edwards−Lawrence Heikkilä Palaniappan Khan−Amyotte Srinivasan− Meibao Srinivasan−Nhan Sugiyama


route Andraos (ref23) (ref38) (ref39) (ref40) (ref41) (ref42) (ref26)
1a (ACH) 4 4 4 4 4 4 4 4
2 (C2/PA) 3 3 3 3 3 1 2 2
5 (iC4) 1 2 1 2 2 3 3 1
6 (TBA) 2 1 1 1 1 2 1 3

K DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX
ACS Sustainable Chemistry & Engineering Research Article

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L DOI: 10.1021/acssuschemeng.5b01240
ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

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