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ATOM ECONOMY: A Measure of the Efficiency of a Reaction

A Green Chemistry Module


Suggested Use: An organic chemistry course (both lecture and lab) during a
discussion of various reactions (substitution, elimination, addition, rearrangements,
etc.)
Atom economy (atom efficiency) describes the conversion
efficiency of a chemical process in terms of all atoms involved (desired
products produced). In an ideal chemical process, the amount of
starting materials or reactants equals the amount of all products
generated (see stoichiometry) and no atom is wasted. Recent
developments like high raw material (such as petrochemicals) costs and increased
sensitivity to environmental concerns have made atom economical approaches more
popular. Atom economy is an important concept of green chemistry philosophy,[1][2][3]
and one of the most widely used ways to measure the "greenness" of a process or
synthesis.
Atom economy can be written as:

% 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

1.33 g of sodium bromide (2) in 1.5 mL of water, followed by addition of 0.80 mL of


1-butanol (1) and 1.1 mL (2.0 g) of concentrated sulfuric acid (3). The following
Reagents Table (Table 1) and Desired Product Table (Table 2) can then be

Table 1 Reagents Table

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

Table 2 Desired Product Table

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

Other Environmental Considerations


Although consideration of both the atom economy and the % yield, gives a much
better measure of the efficiency of a reaction and its environmental acceptability,
other factors need to be considered. To prompt a discussion of the environmental
acceptability of a reaction it is prudent to study some of the Twelve Principles of
Green Chemistry (see below). Principle numbers 1 and 2 are directly addressed by
atom economy and yield.
THE TWELVE PRINCIPLES OF GREEN CHEMISTRY4
1. It is better to prevent waste than to treat or clean up waste after it is
formed.
2. Synthetic methods should be designed to maximize the incorporation
of all materials used in the process into the final product.
3. Wherever practicable, synthetic methodologies should be designed to
use and generate substances that possess little or no toxicity to human
health and the environment.
4. Chemical products should be designed to preserve efficacy of function
while reducing toxicity.
5. The use of auxiliary substances (e.g. solvents, separation agents, etc.)
should be made unnecessary whenever possible and, innocuous when
used.
6. Energy requirements should be recognized for their environmental and
economic impacts and should be minimized. Synthetic methods
should be conducted at ambient temperature and pressure.

7. A raw material feedstock should be renewable rather than depleting


whenever technically and economically practical.
8. Unnecessary derivatization (blocking group, protection/deprotection,
temporary modification of physical/chemical processes) should be
avoided whenever possible.
9. Catalytic reagents (as selective as possible) are superior to
stoichiometric reagents.
10. Chemical products should be designed so that at the end of their
function they do not persist in the environment and break down into
innocuous degradation products.
11. Analytical methodologies need to be further developed to allow for
real-time in-process monitoring and control prior to the formation of
hazardous substances.
12. Substances and the form of a substance used in a chemical process
should chosen so as to minimize the potential for chemical accidents,
including releases, explosions, and fires.
Principles 3 and 4 deal with the toxicity of all substances used in a reaction including
the reactants and products. Considering Equation 1 it is clear that the two
hydrogens and one oxygen that go into the formation of water are wasted. However
if a reaction is going to form a waste product, then water is about as
environmentally benign (nontoxic and presents no disposal problem if it is pure) as
can be imagined. However all the products and the reactants should be evaluated
for their toxicity. Excellent examples of the formation of less toxic products that have
the same efficacy, are seen in new pesticides developed by Rohm and Haas for
controlling insects and for controlling marine fouling organisms. Each of these new
examples of pesticides have won a Presidential Green Chemistry Challenge award.
Principle #5 prompts the consideration of auxiliary substances (solvents, separation
agents, drying agents etc.) that are used in reactions and syntheses. Although water
is used as the solvent (an environmental plus5), in a typical experimental procedure1
to carry out Equation 1, workup of the product (1-bromobutane) after distillation
requires 1 mL of concentrated sulfuric acid, 1 mL of 3M sodium hydroxide,
anhydrous calcium chloride, 1 mL of ethanol, 1 mL of acetone and 2 mL of p-xylene
all to isolate only 1-1.2 g of 1-bromobutane! It is thus clear that the waste generated
from these auxiliary substances is significant and exceeds the amount of waste (at
least from a mass point of view) that is generated directly from the reaction. Many
organic reactions utilize large amounts of organic solvents which are frequently
toxic. These solvents often find their way into the water, soil and air resulting in
significant pollution of the environment. Efforts are underway to replace organic
solvents with water, carbon dioxide and room temperature ionic liquids. In fact
Joseph DeSimone of the University of North Carolina has been awarded a
Presidential Green Chemistry Challenge award for his work in developing surfactants
for liquid and supercritical carbon dioxide. As a result of Dr. DeSimone's efforts, a
process using liquid carbon dioxide has been developed for the dry cleaning of

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

Table 5 Atom Economy 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

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (56/205) X 100 = 27%
economy is a result not only of the loss of the HBr but also because this is a base
promoted reaction and all of the atoms of the sodium ethoxide base are found in
unwanted side products.
Atom Economy in Addition Reactions
Because addition reactions in general lead to the incorporation of all the atoms of
the reactants into the final desired products, addition reactions result in high atom
economy. From an atom economy point of view, addition reactions are thus

environmentally preferable to elimination and substitution reactions. As a case in


point consider the following addition of hydrogen bromide to methyl propene. In this
example all the atoms of the reactants (9 and 11) are shown in green since all of
these atoms are utilized in the final desired product (7). The table of atom economy
(Table 6) and the calculation of 100% atom economy further emphasize the
excellent atom economy of this reaction.
Equation 3

Table 6 Atom Economy Equation 3

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

____

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (137/137) X 100 = 100%
Atom Economy in Rearrangement Reactions
Rearrangement reactions involve reorganization of the atoms of a molecule.
Because neither elimination, addition or substitution of atoms is taking place, in the
molecule undergoing rearrangement, the atom economy of rearrangement reactions
is 100% and they are environmentally preferable reactions from an atom economy
standpoint. To illustrate this, consider the acid catalyzed rearrangement of 3,3dimethyl-1-butene (12) to 2,3-dimethyl-2-butene (13). In this case the atoms of the
reactant 12 are all shown in green since they are all incorporated into the desired
product 13. As in the previous examples one can set up an atom economy table and
calculate the % atom economy. Although the acid (H+) used in this reaction is not
incorporated into the desired product it is used only in catalytic amounts and
therefore indicated in black (not green or brown) and it is not considered in the atom
economy table or the calculation of the atom economy. As was predicted above for
rearrangements, the % atom economy of this reaction is 100%.
Equation 4

Table 7 Atom Economy Equation 4

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

____

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (84/84) X 100 = 100%
Virtually all organic reactions fall into the categories of substitution, addition,
elimination or rearrangement reactions. From the perspective of atom economy,
addition and rearrangement reactions are environmentally preferable, with
substitution reactions next, while eliminations are the least environmentally
preferable. As one encounters reactions, in the study of chemistry, one should
examine each reaction from the point of not only the yield, but also the atom
economy of the reaction.
Atom Economy in Syntheses
The concept of atom economy can also be applied to syntheses. To determine the
atom economy of a synthesis, one simply must determine which of the atoms of the
reactants for all steps in the synthesis are incorporated into the desired final
product.
The Synthesis of Ethylene Oxide
To illustrate the concept of atom economy in a synthesis, consider the industrial
synthesis of ethylene oxide (19). Ethylene oxide is a feedstock in the synthesis of
ethlyene glycol (used in antifreeze), ethoxylates (surfactants), and glycol ethers and
polymers (such as PET). Approximately 8,800 million pounds of this compound are
prepared per year on a global basis. The classical synthesis (Scheme 1) of ethylene
oxide (19) is a two-step synthesis and is known as the chlorohydrin route. The atoms
of the reactant atoms that are incorporated into the final desired product (19), and
the atoms of the desired product are

Scheme 1 The Clorohydrin Route to Ethylene Oxide

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

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (44/189) X 100 = 23%
A catalytic route (Scheme 2) to ethylene oxide from ethylene has been developed. In
this one step synthesis the only other reagent, aside from ethylene, that is used is
1/2 mole of oxygen. As can be seen from Scheme 2 and Table 9 all of the reagent
atoms are incorporated into the desired final product and thus this synthesis has
100% atom economy. The atom economy of 100% for this reaction is not suprising
since this is an addition reaction and as was indicated preciously, addition reactions
have 100% atom economy.
Scheme 2 The Catalytic Route to Ethylene Oxide

Table 9 Atom Economy of Scheme 2, The Catalytic Route to Ethylene Oxide

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

_____

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (44/44) X 100 = 100%
The Synthesis of Ibuprofen
The Boots Company Synthesis of Ibuprofen
Ibuprofen is the active ingredient in a number of brand name products including
Advil, Motrin and Nuprin. Ibuprofen acts as an analgesic (pain reliever) and is also
effective as a Non Steroidal Anti-Inflammatory Drug (NSAID). NSAIDs reduce
inflammation from such conditions as arthritis, osteoarthritis and rheumatism.
Ibuprofen is referred to as a non steroidal anti-inflammatory drug since ibuprofen is
not a member of the steroid family of compounds.
The world production of ibuprofen exceeds 30 million pounds per year. The Boots
Company PLC of Nottingham, England first patented the synthesis of ibuprofen in
the 1960's (U.S. Patent 3,385,886) and this has served as the main method of
synthesis for many years. The Boot's synthesis of ibuprofen is a six-step synthesis
and is shown in Scheme 3. As usual all the
Scheme 3 The Boots Synthesis of Ibuprofen

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

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (206/514.5) X 100 = 40%
The BHC Company Synthesis of Ibuprofen
In the eighties ibuprofen was approved for over-the-counter use and the Boots
Company patent expired. Recognizing the financial opportunities that the
manufacture and sales of this drug could offer, several companies embarked upon
setting up facilities and developing new methods for the preparation of ibuprofen.
The Hoechst Celanese Corporation (Somerville, NJ; now know as the Celanese
Corporation) discovered a new three-step synthesis of ibuprofen. Together with the
Boots Company they formed the BHC Company to prepare (by the new synthesis)
and market ibuprofen. The BHC Company synthesis is show in Scheme 4 with the
utilized atoms in green and the untutilized atoms in brown. The atom economy is
further illustrated in Table 11 and calculation of the % atom economy gives 77%, a
significant improvement over the 40% of the
Scheme 4 The BHC Company Synthesis of Ibuprofen

Table 11 Atom Economy of Scheme 4, the BHC Company Synthesis of Ibuprofen

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

% Atom Economy = (FW of atoms utilized/FW of all reactants) X 100


= (206/266) X 100 = 77%

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

1. Define the following terms


a) atom economy
b) % atom economy
c) % yield
d) % experimental atom economy
c) %PE .EAE
2. Which of the terms in question 1 are only meaningful with experimental results?
What experimental result is necessary
to make these terms meaningful?
3. Consider the following reactions.
a) Label each reaction as a substitution, elimination, addition or rearrangement.
b) Rewrite each reaction making sure that the 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, analogous to Table 3, for each reaction .
d) Calculate the % atom economy of each reaction.

4. As indicated in reference 3, Roger Sheldon has developed a term very similar to


the % atom economy called % atom
utilization. The % atom utilization can be calculated according to the following
equation.
% Atom Utilization = (MW of desired product/MW of all products) X 100
a) Compare and contrast this with the % atom economy.
b) With the information given in Schemes 3 and 4 can you calculate the % atom
utilization for these syntheses? Explain your
answer.
c) What concept that you learned in freshman chemistry makes the actual
percentages calculated for the %
atom utilization, and % atom economy equal (under most circumstances). Prove this
by calculating the % atom utilization for
each of the reactions in question 3 and comparing your results to the % atom
economy that you calculated in question 3.

5. Consider the following two-step synthesis of 2-pentyne.

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.