Safety and Environmental Considerations - Fundamentals of Industrial Chemistry: Pharmaceuticals, Polymers, and Business - page 248

Because the potential for fires, explosions, and releases is minimized, this
also adheres to green principle 12.
There are certain metrics used in Green Chemistry. One is associated with
principle two: Synthetic methods should be designed to maximize the incor-
poration of all materials used in the process into the final product. That is
the metric of atom economy [14]. Atom economy is the mass of the product
divided by the sum of the mass of all the reactants. Ideally this number is one
and the closer to one the better. Atom economy does not take into account
solvent or other reagents such as bases. Another metric is the Environmental
factor or E-factor [15]. The E-factor is the mass of the total waste divided by
the mass of the product. Ideally the E-factor should be zero and the smaller the
number, the better. However, some fine chemical or pharmaceutical synthe-
ses have E-factors of about one hundred. Using micelles, the Lipshutz group
reduced the E-factor of a Heck reaction from 137 to 7.5 and then even lower
with recycle [16]. Consider the following experimental procedure [17].

N-Methyl-2-nitro-N-phenylaniline (7c). To a solution of aniline 6c (0.182 g,
1.0 mmol) in DMF (5 mL) at rt was added freshly crushed KOH (0.252 g,
4.5 mmol). After 10 min, MeI (0.20 mL, 3 mmol) was added to the stirring
mixture dropwise via syringe. Stirring was continued at rt until TLC showed
consumption of the aniline starting material. The reaction was then quenched
with 25 mL of deionized H 2 O and extracted with 3 30 mL of EA. The organic

layers were combined and dried over MgSO 4 . The solvent was removed under
reduced pressure and no further purification was needed to obtain the nor-halo
N-methyl derivative 7c as a brown oil (0.194 g, 100% yield).

×

CH 3

N

N

O 2 N O 2 N

6c 7c

We can calculate the atom economy by dividing the mass of the product by
the sum of the mass of all the reactants. Three mmol of methyl iodide (molec-
ular weight = 141.94g/mol) has a mass of 0.426 g so the equation becomes:

0 . 194 ∕( 0 . 182 + 0 . 426 )= 0 . 32

We can also calculate the E-factor. The mass of the ingredients are as fol-
lows:

0.182 g aniline 6C
(5 mL)(0.944g/mL) = 4.72 g DMF