Chapter 3: Atom Economy
Green Context: A central concept in green engineering is to minimize the complexity of
the reaction sequences used for the production of new molecules. One way in which this
is determined is through a measure of atom economy. Atom economy is defined as the
percentage of the raw materials and reagents used in the synthesis that actually end up in
the final product. The more of the material that remains in the product, the less that is
disposed of as waste.
Problem Scope: This problem illustrates the concept of atom economy through the use
of a new reaction pathway that was developed for the synthesis of ibuprofen, an
important pharmaceutical product. This process was named a Presidential Green
Chemistry Challenge recipient in 1997.
Problem Statement:
BHC Company developed a new synthetic process to manufacture ibuprofen, a wellknown, nonsteroidal, anti-inflammatory painkiller marketed under brand names such as
Advil™ and Motrin™. Commercialized since 1992 in BHC's 3,500 metric-ton-per-year
facility in Bishop, Texas, the new process was cited as an industry model of
environmental excellence in chemical processing technology. For its innovation, BHC
was the recipient of the Kirkpatrick Achievement Award for "outstanding advances in
chemical engineering technology" in 1993. This process was awarded a Presidential
Green Chemistry Challenge Award in 1997.
The new technology involves only three catalytic steps, with approximately 80 percent
atom utilization (virtually 99 percent including the recovered byproduct acetic acid) and
replaces technology with 6 stoichiometric steps and less than 40 percent atom utilization.
The use of anhydrous hydrogen fluoride as both a catalyst and solvent offers important
advantages in reaction selectivity and waste reduction. As such, this chemistry is a model
of source reduction, the method of waste minimization that tops EPA's waste
management hierarchy. Virtually all starting materials are either converted to product or
reclaimed byproduct, or are completely recovered and recycled in the process. The
generation of waste is practically eliminated.
The BHC Process for the
manufacture of Ibuprofen:
O
H3C
H3C
The BHC process replaces the
original Boots process, patented in
the mid-1960’s. The Boots
process consisted of six steps,
some of which included
substantial derivatization.
O
O
CH3
H3C
HF
CH3
CH3
CH3
H
O
Raney
Nickel
H2
H 3C
H 3C
CO/Pd
CH3
COOH
CH3
CH3
CH3
OH
The Boots process for the manufacture of ibuprofen:
O
H3 C
H 3C
CH3
H
O
O
CH3
H3 C
AlCl3
CH3
CH3
H3C
O
CH3
NaOC2H5
COOH
CH2ClCOOC2H5
CH3
H3C
- NH3
CH3
CH3
COOC2H5
H3 C
N
O
CH3
H+
H 3C
OH
H3C
N
CH3
- H2O
H2O
O
NH2OH
CH3
In terms of atom economy, determine which method of the synthesis of Ibuprofen is
preferred. Atoms appearing in red are atoms that are wasted.