In: Chemistry
from the three isomers of 1,2-dibromo-1,2-diphenylethane.
1) Name one green chemistry principle for which each reaction shows improvement over the traditional process, one for which each reaction is less favorable compared to the traditional process and explain how they apply to the reactions.
Atom economy in syntheses
The concept of atom economy can also 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.
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 | Utilized Atoms | Weight of Utilized Atoms |
Unutilized Atoms |
Weight of Unutilized Atoms |
1 C10H14 | 134 | 10C,13H | 133 | H | 1 |
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 | _____ | 0 | 2C,5H,O,Na | 68 |
7 H3O | 19 | _____ | 0 | 3H,O | 19 |
9 NH3O | 33 | _____ | 0 | 3H,N,O | 33 |
12 H4O2 | 36 | H,2O | 33 | 3H | 3 |
Total 20C,42H,N,10O, Cl,Na |
514.5 | Ibuprofen 13C,18H,2O |
Ibuprofen 206 |
Waste Products 7C,24H,N,8O, Cl,Na |
Waste Products 308.5 |
% 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 |
Unutilized Atoms |
Weight of Unutilized Atoms |
1 C10H14 | 134 | 10C,13H | 133 | H | 1 |
2 C4H6O3 | 102 | 2C,3H,O | 43 | 2C,3H,2O | 59 |
4 H2 | 2 | 2H | 2 | _____ | 0 |
6 CO | 28 | CO | 28 | _____ | 0 |
Total 15C,22H,4O |
266 | Ibuprofen 13C,18H,2O |
206 | Waste Products 2C,3H,2O |
60 |
% 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.