Chemistry Reference
In-Depth Information
having the structure of substituted ureas with amino acid groups have been re-
ported [724, 725].
O
1000
O
O
OH
O
NH
O
O
O
O
O
O
2`
O
O
O
O
OH
H
thermolysin
tert-amyl alcohol
45°C, 48 h
H
O
O
O
777
1. step
O
O
O
OH
O
NH
O
2`
O
O
H
H
O
O
O
O
O
O
O
O
2. step
83 %
O
O
1001
Ureas have hitherto been synthesized mainly by methodologies based on the use
of traditional reagents such as phosgene and isocyanates. In the last few years,
however, these reagents have been increasingly substituted by alternative cleaner
and inherently safer compounds, since the goal of modern environmentally
friendly synthetic chemistry is the development and optimization of reaction con-
ditions to reduce or eliminate the use and production of hazardous materials while
maximizing energy usage [726].
The majority of the most important of the wide variety of methods for preparing
mono-, di-, and trisubstituted ureas [723, 727] fall into three main groups [728].
In the first group, primary amines are reacted with carbonyl insertion com-
pounds such as phosgene [727, 729], and sometimes phosgene substitutes such as
triphosgene [507], various carbonates [503, 730, 731], bis(4-nitrophenyl)carbonate
[503], di-tert-butyl dicarbonate [664], S,S-dimethyl thiocarbonate [577], and N,N
-
carbonyldiimidazole [732], 1,1-carbonylbis(benzotriazole) [728], and trihaloacetyl
chlorides. Most of these compounds have been utilized as safer reagents that can
be stored and handled without special precautions.
O
