300 Green Chemistry, 2nd ed
syntheses including preparation of analgesics such as Ibuprofen. The dimethyl sulfate
reagent used to accomplish the methylation poses toxicity problems in that it is a known
primary carcinogen (a compound that does not require bioactivation to cause cancer).
The reaction also produces a byproduct of Na 2 SO 4 , which if contaminated with dimethyl
sulfate reagent may pose disposal problems.
Dimethyl carbonate prepared by reacting methanol, CH 3 OH, with carbon monoxide,
CO, in the presence of elemental oxygen and a copper salt catalyst has been developed
as a green alternative to dimethyl sulfate as a methylating reagent. When dimethyl
carbonate acts as a methylating agent,
N (11.9.4)
CH 3
H
R
C CH 3
O
N H 3 C O O
H
H
R
H OH
H
H
C
Dimethyl carbonate(^2) +
(^2) +CO
2 +
methanol and innocuous carbon dioxide are generated as byproducts. The methanol can
be recirculated through the system to generate addional dimethyl carbonate reagent.
Media
Chemical reactions are often carried out in media, usually organic solvents or
water. The major role of a solvent in chemical reactions is to provide a medium in which
feedstocks and reagents can dissolve and come into close, rapid contact at the molecular
level. Substances dissolved in a solvent are solvated by binding of the solvent to the
molecules or ions of the dissolved substance, the solute. Because of its polar nature and
the ability to form hydrogen bonds (see Chapter 7, Section 7.1 and Figure 7.1), water
is a particularly good solvent for ionic compounds — acids, bases, and salts. However,
many organic feedstocks and reagents are not soluble in water or are decomposed by it,
so organic solvents have to be used as reaction media.
Many of the environmental and health problems associated with making chemicals
are the result of the use of organic solvents as media. Hydrocarbon solvents will burn and
hydrocarbon vapors in air are explosive. Although many hydrocarbon solvents are not
particularly toxic, some can cause the condition of peripheral neuropathy mentioned in
Section 11.8, and benzene is regarded as a carcinogen thought to cause leukemia. Released
to the atmosphere, hydrocarbons can also participate in photochemical processes leading
to the formation of photochemical smog (see Chapter 8, Section 8.10).
One approach to making chemical synthesis processes greener is to replace specific
solvents with less hazardous ones. For this reason, toxic benzene solvent is replaced by
toluene wherever possible. As shown by their structural formulas below, toluene has a
methyl group, -CH 3 , that benzene does not have. The methyl group in toluene can be
acted upon by human metabolic systems to produce a harmless metabolite (hippuric