Professional Documents
Culture Documents
% atom economy =
Note that atom economy can be poor even when chemical yield is near 100%, see
for instance the Cannizzaro reaction or the Wittig reaction. If the desired product has
an enantiomer the reaction needs to be sufficiently stereoselective even when atom
economy is 100%. A Diels-Alder reaction is an example of a potentially very atom
efficient reaction that also can be chemo-, regio-, diastereo- and enantioselective.
Catalytic hydrogenation comes the closest to being an ideal reaction that is
extensively practiced both industrially and academically.[4] The Gabriel synthesis of
amines is an example of extremely low atom economy, as stochiometric quantities
of phthalic acid derivatives are formed. In most cases, the atom economy of the
Gabriel synthesis is <<50%.
Atom economy can also be adjusted if a pendant group is recoverable, for example
Evans auxiliary groups. However, if this can be avoided it is more desirable, as
recovery processes will never be 100%. Atom economy can be improved upon by
careful selection of starting materials and a catalyst system.
Atom economy is just one way to evaluate a chemical process. Other criteria can
include energy consumption, pollutants released and price.
Poor atom economy is common in fine chemicals or pharmaceuticals synthesis, and
especially in research, where the aim to readily and reliably produce a wide range of
complex compounds leads to the use of versatile and dependable, but poorly atomeconomical reactions. For example, synthesis of an alcohol is readily accomplished
by reduction of an ester with lithium aluminum hydride, but the reaction necessarily
produces a voluminous floc of aluminum salts, which have to be separated from the
product alcohol and disposed of. The cost of such hazardous material disposal can
be considerable. Catalytic hydrogenolysis of an ester is the analogous reaction with
a high atom economy, but it requires catalyst optimization, is a much slower
reaction and is not applicable universally.
Creating reactions utilizing atom economy
It is fundamental in chemical reactions of the form A+B C+D that two products are
necessarily generated though product C may have been the desired one. That being
the case, D is considered a byproduct. As it is a significant goal of green chemistry
to maximize the efficiency of the reactants and minimize the production of waste, D
must either be found to have use, be eliminated or be as insignificant and innocuous
as possible. With the new equation of the form A+BC, the first step in making
chemical manufacturing more efficient is the use of reactions that resemble simple
addition reactions with the only other additions being catalytic materials.
Efficiency of a Reaction
Percentage Yield
Although the efficiency of a reaction can be measured in many ways, by far the most
common way is to calculate the yield (percentage yield). Students are often
required, especially in laboratory, to determine the theoretical yield based upon the
limiting reagent and then to calculate the percentage yield based upon the ratio of
the actual yield/theoretical yield X 100. In general organic chemists consider yields
of 90% or better as excellent while 20% or less are poor.
It refers to the product from chemical reaction: the quantity of product
resulting from a chemical reaction or process, often expressed as a percentage of
the amount that is theoretically obtainable
Theoretical yield = (moles of limiting reagent)(stoichiometric ratio; desired
product/limiting reagent)(MW of desired product)
Percentage yield= (actual yield/theoretical yield) X 100
In order to illustrate the calculation of the percentage yield (and the measurement
of the efficiency of a reaction) consider the following acid promoted nucleophilic
substitution reaction. A typical procedure1 for this reaction begins with dissolving
Equation 1a
Reagent
MW
Weight
Used (g)
Moles Used
Theoretical
Moles Needed
1 C4H9OH
74.12
0.80
0.0108
0.0108
2 NaBr
102.91
1.33
0.0129
0.0108
3 H2SO4
98.08
2.0
0.0200
0.0108
Density
0.810
Bp (oC)
118
1.84
Compoun
Theoretical Yield
MW
d
(Moles)
Theoretical
Actual Yield
Yield
(Grams)
(Grams)
4 C4H9Br
1.48 (100%)
137.03
0.011
1.20
%
Yield
Densit Bp
y
(oC)
81 1.275
101.6
setup. Dividing the weight of each reactant that is used, by the molecular weight of
the reactant, gives the number of moles of each reagent used. From the
stoichiometry of the reaction (Equation 1a) it is clear that one mole of each reactant
is required to produce one mole of product (1-bromobutane) and since 1-butanol
(0.0108 mole) is used in the smallest amount it is the limiting reagent. Calculation of
the (as shown below) theoretical yield of 1-bromobutane gives 1.48 g. This means
that using the
Theoretical yield = (moles of limiting reagent)(stoichiometric ratio; desired
product /limiting reagent)(MW of desired product)
= (moles of 1-butanol)(stoichiometric ratio; 1-bromobutane/1-butanol)(MW of 1bromobutane)
=(0.0180 mole)(1 mole / 1 mole)(137.03 g/mole)
=1.48 g
above quantities of reagents the maximum amount (assuming 100% yield) of 1bromobutane that can be produced is 1.48 g. In fact no reaction ever proceeds with
100% yield due to such factors as the formation of side products, incomplete
conversion of the starting materials, loss upon workup of the reaction mixture, and
loss upon isolation and purification of the desired product. This reaction typically
produces actual yields of 1-1.2 g. Assuming that the actual yield is 1.20 g calculation
of the % yield is as follows. Thus 81% of the theoretical yield is actually isolated,
which is a very respectable yield, that would please most chemists.
Percentage yield= (actual yield/theoretical yield) X 100
= (1.20 g/1.48 g) X 100 = 81%
Atom Economy in a Substitution Reaction
As indicated previously most chemists have traditionally measured the efficiency of
a reaction by the percentage yield, however this only tells part of the story. If one
considers the above reaction where a total of 4.13 g of reactants (0.8 g of 1-butanol,
1.33 g of NaBr and 2.0 g of H2SO4) was used, and that at best this reaction will only
yield 1.48 g of the desired product, the question might be asked "what happens to
the bulk (4.13 g -1.48 g = 2.7 g) of the mass of reactants?". The answer is they end
up in side products (NaHSO4 and H2O) that may be unwanted, unused, toxic and/or
not recycled/reused. The side products are oftentimes treated as wastes and must
be disposed of or otherwise treated. At best only 36% (1.48 g/4.13 g X 100) of the
mass of the reactants end up in the desired product. If the actual yield is 81% then
only 29% (.81 X .36 X 100) of the mass of the reactants actually ends up in the
desired product!
In an effort to foster awareness of the atoms of reactants that are incorporated into
the desired product and those that are wasted (incorporated into undesired
products), Barry Trost developed the concept of atom economy.2 In 1998 Trost was
awarded a Presidential Green Chemistry Challenge Award for the concept of atom
economy. In light of the concept of atom economy, the above acid promoted
nucleophilic substitution must now be reconsidered. In Equation 1b we have
illustrated the atom economy of this reaction by showing all of the reactant atoms
that are incorporated into the desired product in green,
Equation 1b
while those that are wasted are shown in brown. Likewise the atoms of the desired
product are in green and the atoms composing the unwanted products are in brown.
Table 3 provides another view of the atom economy of this reaction. In columns 1
and 2 of this table, the formulas and formula weights (FW) of the reactants are
listed. Shown in green (columns 3 and 4) are the atoms and weights of the atoms of
the reactants that are incorporated into the desired product (4), and shown in brown
(columns 5 and 6) are the atoms and weights of atoms of the reactants that end up
in unwanted side products. Focusing on the last row of this table it can be seen that
of all the atoms of the reactants (4C, 12H, 5O, 1Br, 1Na and 1S) only 4C, 9H, and 1Br
are utilized in the desired product and the bulk (3H, 5O, 1Na, 1S) are wasted as
components of unwanted products. This is an example of poor atom economy! A
logical extension of Trost's concept of atom economy is to calculate
Table 3 Atom Economy of Equation 1
Reagents
Formula
Reagents
FW
Utilized
Atoms
Weight of
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
1 C4H9OH
74
4C,9H
57
HO
17
2 NaBr
103
Br
80
Na
23
3 H2SO4
98
_____
2H,4O,S
98
Total
275
4C,9H,Br
137
3H,5O,Na,S
138
4C,12H,5O,BrNaS
the percentage atom economy.3 This can be done by taking the ratio of the mass
of the utilized atoms (137) to the total mass of the atoms of all the reactants (275)
and multiplying by 100. As shown below this reaction has only 50% atom economy.
% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100
= (137/275) X 100 = 50%
Thus at best (if the reaction produced 100% yield) then only half of the mass of the
reactants would be incorporated into the desired product while the rest would be
wasted in unwanted side products.
OPTIONAL MATERIAL
The following optional material deals with two new terms called the "experimental"
atom economy, and the "Percentage Yield X Experimental Atom Economy". These
two terms further elucidate the efficiency of a reaction however this material may be
omitted. To skip the optional material and return to the discussion of the atom
economy and other environmental considerations click here.
In reality if the reaction is performed according to the quantities indicated in Table 1
the atom economy would be even less. This is a result of the fact that in Table 3 it
was assumed the stoichiometric amounts of each reactant (1:1:1), as indicated in
Equation 1b, would be consumed in this reaction. In fact the amounts of reactants 1,
2 and 3 that were used in the actual reaction, as shown in Table 1, are
0.0108:0.0129:0.0200 = 1:1.11:1.85. Table 4 illustrates a term that we have coined
the "experimental" atom economy, which is based on the actual quantities of
reagents used in the experiment. Table 4 is similar to Table 3 with the exception that
Table 4 Experimental Atom Economy of Equation 1: Based on Actual
Quantities of Reagents Used
Reagents
Formula
1 C4H9OH
2 NaBr
Weight of
Reagent
(FW X
moles
used)
Utilized
Atoms
74.0 X .0108
= .80
103 X .
0129=1.33
Weight of Utilized
Atoms (FW X
moles)
4C,9H
Br
Unutilize
Weight of Unutilized
d
Atoms (FW X moles)
Atoms
57 X .0108= .
62
79.9X .
0129=1.03
79.9X .
0108=0.86
HO
17 X .0108=.18
Na
23 X .0129=.30
excess 0.17
subtotal 0.47
excess 0.17
3 H2SO4
98 X .0200=
2.0
Total
4C,12H,5O,BrN 4.13
aS
_____
0.00
4C,9H,B
1.48
r
2H,4O,S
98.1 X .
0200=1.96
3H,5O,Na,
2.61
S
the excess of any reagents that are used is accounted for. In this case the NaBr
(reagent 2) is used in excess (.0129 mole) as compared to the 1-butanol (.0108
mole), which is the limiting reagent. Thus in Table 4 in the fourth column where the
mass of the reagents that are actually used is calculated, it can be seen that even
though the bromine (from the NaBr) is utilized in the desired product there is an
excess of this element and therefore the excess must be added into the unutilized
weight of reagents. A term we have coined called the Percentage Experimental
Atom Economy can now calculated. The percentage experimental atom economy is
simply the expected mass of the reagents that are utilized in the desired product
(which works out to be the same as the theoretical yield), divided by the actual total
mass of all the reagents used in the experiment. In Table 4 we see in column 4, row
4, the utilized mass is 1.48 g and the total mass of the reagents is 4.13 g (row 4,
column 2) thus the % experimental atom economy is (1.48/4.13 X 100) 36%. This is
of course nothing more than the same calculation that was
% Experimental Atom Economy = (mass of reactants utilized in the desired
product/total mass of all reactants) X 100
= (theoretical yield/total mass of all reactants) X 100
= (1.48 g/4.13 g) X 100 = 36%
performed at the beginning of the discussion of atom economy and this represents
the maximum % of the mass of the reactants that can be incorporated into the
desired product. Although the same conclusion was obtained before a discussion of
the concept of atom economy, it is helpful to build a table such as Table 4 so that
one can see which reagent(s) are leading to the poor atom economy.
Rather than consider the percentage yield and (experimental) atom economy
separately, an even better indication of the efficiency of a reaction is to consider a
combination of the two. We have coined the term Percentage Yield X
Experimental Atom Economy (%PE .EAE) to illustrate this. This is calculated as
follows:
% Yield X Experimental Atom Economy = (actual yield/theoretical yield) X (mass
of reactants utilized in the desired
product/total mass of all reactants) X 100
%PE .EAE= (actual yield/theoretical yield) X (theoretical yield/total mass of all
reactants)
X 100
= (actual yield/total mass of all the reactants) X 100
= (1.20 g/4.13 g) X 100
= 29%
Notice, that in this calculation, the theoretical yield cancels leaving the ratio of the
actual yield to the total mass of all the reactants X 100. If again one assumes that
the actual yield is 1.20 g and this is divided by 4.13 g (total mass of all reactants
from Table 4) then the % Yield X Experimental Atom Economy is only 29%
(previously we arrived at this same conclusion in a much less formal way; see the
first paragraph of this section). This means that only 29% of the total mass of all the
reactants is actually isolated in the desired product while 71% is wasted! Measuring
the efficiency of a reaction in this manner puts it into an entirely new perspective.
While many chemists would consider a yield of 81% to be a very acceptable, not
many would consider the isolation of only 29% of the mass of the reactant atoms in
the desired product to be satisfactory.
This concludes the optional material
clothes. This process recycles the carbon dioxide, that is obtained as waste from
other chemical procedures and allows for the replacement of perchloroethylene, the
health effects of which have come into question.
Principle #6 considers the energy requirements of a reaction. It is preferable to
perform reactions at ambient temperature and pressure, however many chemical
reactions require heating and/or cooling and pressures other than that of the
surroundings. This necessitates the use of some energy source and most often this
energy source is a fossil fuel. In order to perform the reaction and isolate the 1bromobutane formed in Equation 1, a reflux and two distillations are required. Thus
the energy requirements of this reaction are significant.
Most organic starting materials, such as the 1-butanol in Equation 1, are ultimately
derived from crude oil, a nonrenewable (depleting) resource. Principle #7 urges us
to consider whether these starting materials can be derived from renewable
resources. Renewable resources generally means biological and plant based
materials (biomass). Carbon dioxide and methane are also generally considered to
be renewable since they can be generated from both natural and synthetic methods.
Work by Draths and Frost at Michigan State, Mark Holtzapple at Texas A&M, and
Biofine Corporation to create chemical feedstocks from biomass have all won
Presidential Green Chemistry Challenge awards.
Some may mistakenly refer to the reaction described in Equation 1 as an acid
catalyzed reaction when in fact it is actually an acid promoted reaction. This is a
result of the fact that the sulfuric acid in this reaction is required in stoichiometric,
not catalytic amounts. As principle #9 indicates reagents used in catalytic amounts
are preferable to reagents used in stoichiometric amounts. Since one mole of
sulfuric acid is required for the loss of every water molecule in this reaction, then
only stoichiometric quantities of this reagent will suffice. However even if
stoichiometric amounts are used then recovery/recycling/reuse of unwanted
products should take place whenever this is feasible. Significant strides have
recently been made to develop reactions that are promoted by nontoxic and
recoverable catalysts. A biocatalytic process discovered and developed by Lilly
Research Laboratories for producing a potential anticonvulsant drug has won a
Presidential Green Chemistry Challenge award.
Atom Economy in Elimination Reactions
In all of the remaining discussions of the efficiency of a reaction, the discussion will
be limited to the atom economy based on the stoichiometry of the reaction. When
one encounters these reactions in the laboratory it may also be prudent to calculate
the atom economy based on the quantities of the reagents used (experimental atom
economy). In addition one may also want to consider matters such as toxicity,
energy use, the use of auxiliary substances, catalytic versus stoichiometric reagents
and renewable versus nonrenewable feedstocks.
In the substitution reaction above (Equation 1a) it was revealed that the poor atom
economy resulted from the fact that the atoms of the leaving group (OH) that is
being replaced, the counterion (sodium) of our nucleophile (bromide), and the
sulfuric acid that is required for this reaction all are wasted in forming unwanted
products in this reaction. By virtue of the fact that elimination reactions require only
the loss of atoms (while gaining none) from the reactant, means that elimination
reactions are in general even worse, in terms of their atom economy, than
substitution reactions.
As an example consider the atoms of the following elimination reaction. Base
promoted dehydrohalogenation of alkyl halides is a common method of producing
alkenes from alkyl halides via elimination. In Equation 2 the formation of methyl
propene is accomplished by the reaction of 2-bromo-2-methylpropane (7) with
sodium ethoxide (8). In this reaction, the atoms of the reactants that are
incorporated into the desired product (9) and the atoms of the desired product are
indicated in green, while the unutilized atoms of the reactants are shown in brown
as are the atoms in the unwanted products of the reaction. Table 5 illustrates the
atom economy of this reaction and calculation of the % atom economy gives a very
poor 27%. The poor atom
Equation 2
Reagents
Formula
Reagents
FW
Utilized
Atoms
Weight of
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
7 C4H9Br
137
4C,8H
56
HBr
81
8 C2H5ONa
68
____
2C,5H,O,Na
68
Total
6C,14H,O,Br,Na
205
4C,8H
56
2C,6H,O,Br,Na
149
Reagents
Formula
9 C4H8
Reagents
FW
56
Utilized
Atoms
Weight of
Utilized
Atoms
4C,8H
Unutilize Weight of
d
Unutilized
Atoms
Atoms
56
____
0
0
0
11 HBr
81
HBr
81
____
Total
4C,9H,Br
137
4C,9H,Br
137
____
Reagents
Formula
Reagents
FW
Utilized
Atoms
Weight of
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
12 C6H12
84
6C,12H
84
____
Total
6C,12H
84
6C,12H
84
____
green, and
those atoms of the shown in green, while the atoms of the reactants that find their
way into unwanted products (along with the atoms of the unwanted products) are
shown in brown. Table 8 is the table of atom economy for the chlorohydrin route to
ethylene oxide and allows one to calculate the poor atom economy (23%) of this
route.
Table 8 Atom Economy of Scheme 1, The Clorohydrin Route to Ethylene Oxide
Reagents
Formula
Reagents
FW
Utilized
Atoms
Weight of
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
28
2C,4H
28
_____
15 Cl2
71
_____
2Cl
71
6 H2O
18
16
2H
18 Ca(OH)2
72
_____
Ca,4H,2O
72
Total
2C,8H,3O,Ca,2Cl
189
2C,4H,O
44
6H,2O,Ca,2Cl
145
14 C2H4
Reagents
Formula
Reagents
FW
Utilized
Atoms
Weight of
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
14 C2H4
28
2C,4H
28
_____
21 1/2 O2
16
16
_____
Total
2C,4H,1Ol
44
2C,4H,O
44
_____
atoms of each reagent that are incorporated into the final desired product
(ibuprofen) are shown in green and those that end up in unwanted products are
shown in brown. Table 10 illustrates the atom economy of the Boots Company
synthesis and allows one to calculate a percentage atom economy of 40%. As was
indicated above about 30 million pounds of ibuprofen are manufactured on a yearly
basis. If all the world's supply of ibuprofen were manufactured by the Boots process,
then this would generate about 35 million pounds of waste!
Table 10 Atom Economy of Scheme 3, the Boots Company Synthesis of Ibuprofen
Reagents
Formula
Reagents
FW
Weight of
Utilized
Atoms
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
1 C10H14
134
10C,13H
133
2 C4H6O3
102
2C,3H
27
2C,3H,3O
75
4 C4H7ClO2
122.5 C,H
13
3C,6H,Cl,2O
109.5
5 C2H5ONa
68
_____
2C,5H,O,Na
68
7 H3O
19
_____
3H,O
19
9 NH3O
33
_____
3H,N,O
33
12 H4O2
36
H,2O
33
3H
Total
20C,42H,N,10O,
Cl,Na
514.5
Waste Products
Ibuprofen
Ibuprofen
Waste Products
7C,24H,N,8O,
13C,18H,2O 206
308.5
Cl,Na
Reagents
Formula
Reagents
FW
Utilized
Atoms
Weight of
Utilized
Atoms
Unutilize Weight of
d
Unutilized
Atoms
Atoms
1 C10H14
134
10C,13H
133
2 C4H6O3
102
2C,3H,O
43
2C,3H,2O
59
4 H2
2H
_____
0
0
60
6 CO
28
CO
28
_____
Total
15C,22H,4O
266
Ibuprofen
13C,18H,2O
206
Waste Products
2C,3H,2O
Boots Company process. The atom economy of the BHC Company process jumps to
>99% if one considers that the acetic acid generated in Step 1 is recovered and
used.
Not only does the BHC Company process offer a dramatic improvement in the atom
economy it offers other environmental advantages. These include a three-step
catalytic process vs. the six-step Boots Company process that requires auxiliary
reagents in stoichiometric amounts. For example, the first step in each process
yields the same product (3) from the same reactants (1 and 2). However, the Boots
Company process utilizes aluminum trichloride in stoichiometric amounts (not
accounted for in Table 10) while the BHC Company process uses HF in catalytic
amounts that is recovered and reused repeatedly. The aluminum trichloride
produces large amounts of aluminum trichloride hydrate as a waste product which is
generally landfilled. The nickel and palladium catalysts used in Steps 2 and 3 of the
BHC Company process are also recovered and reused.
Because the BHC Company process is only three steps (vs. six steps for the Boots
Company process) and it has a much improved atom economy, it not only results in
a dramatic decrease in the waste produced it also allows for a greater throughput
(more ibuprofen in less time and with less equipment). These factors translate into
economic benefits for the company as a result of the fact that less money is required
to deal with the waste that is generated and less capital expenditure is required to
produce the same amount of ibuprofen. Thus not only does the environment benefit,
but the company bottom line is strengthened and good public relations can be
reaped as a result of a greener process.
For the development of this synthesis of ibuprofen, the BHC company won a
prestigious Presidential Green Chemistry Challenge award in 1997 and they also won
the prominent Kirpatrick Chemical Engineering Achievement Award6 in 1993. The
Kirpatrick award is given on a biennial basis by Chemical Engineering magazine and
recognizes outstanding group efforts in developing and commercializing process
technology.
Summary
Atom economy and experimental atom economy go beyond the calculation of the
yield of a reaction and offer a second way to measure the efficiency of a reaction
taking into account the utilized and unutilized atoms of the reactants. The
percentage atom economy and the percentage experimental atom economy, give
one the means to quantify the atom economy, and allows for a quantitative
comparison of the atom economy of one reaction (or synthesis) vs. another. Perhaps
the best measure of the efficiency of a reaction is to take into consideration both the
atom economy and the yield by calculating the percentage yield X experimental
atom economy (PE .EAE). Of course in assessing the environmental suitability of a
reaction (or synthesis) not only should one consider the efficiency of the reaction but
also (as discussed above) other factors such as toxicity, the use of auxiliary
substances, energy requirements, feedstock origins, and catalytic vs. stoichiometric
reagents.
Questions
a) Rewrite the synthesis making sure that each reaction is balanced. Show all the
reactant atoms that are incorporated
into the desired product, and the atoms of the desired product in green, and all
other atoms in brown.
c) Set up a table of atom economy for this synthesis analogous to Table 7.
d) Calculate the % atom economy of this synthesis.
e) Calculate the % atom utilization of this synthesis.
.
6. Your instructor will direct you to an experiment in your current laboratory
textbook. With regard to this lab:
a) Write a balanced equation showing the atoms of the reactants that are
incorporated into the desired product and the
atoms of the desired product in green, and all other atoms in brown.
b) Construct a table of atom economy analogous to Table 3.
c) Calculate the % atom economy.
d) Construct a table of experimental atom economy analogous to Table 4.
e) Calculate the experimental atom economy.
f) Assume that this reaction gives 80% yield. Calculate the %PE .EAE.
g) What are the energy requirements of this reaction?
h) Are there auxiliary substances used in this reaction?
i) What reagents are used in stoichiometric amounts?
j) What reagents are used in catalytic amounts?
7. Supply a mechanism for Step 1 of the BHC Company synthesis of ibuprofen. Is this
step acid catalyzed or acid promoted?
8. A third synthesis of ibuprofen, called the ethyl synthesis, is shown below.
a) Rewrite the synthesis showing all the reactant atoms that are incorporated into
the desired product, and the atoms of
the desired product in green, and all other atoms in brown.
c) Set up a table of atom economy for this synthesis analogous to Table 7.
d) Calculate the % atom economy of this synthesis.