Phosgenation Reactions - Phosgenations - page 439

4.5.3.2 Phosphorus-Based Reagents

Phosphorus pentoxide
Dialkyl- and diarylcarbodiimides bearing cyclohexyl, phenyl, p-chlorophenyl, and
p-ethoxyphenyl residues have been synthesized from the corresponding ureas with
phosphorus pentoxide in pyridine, charged with sand, under reflux [1255]. DCC
has been prepared this way within 2.25 h in 76% yield (see also Section 4.5.3.5,
Table 4.48).

Typical procedure. Dicyclohexylcarbodiimide DCC [1255]: A stirred mixture of N,N 0 -
dicyclohexylurea (19.7 g), phosphorus pentoxide (100 g), sand (175 g), and pyridine
(700 mL) was refluxed for 2.25 h. Stirring was no longer possible after about 30
min. The mixture was filtered and the residue was extracted with pyridine (100
mL). Pyridine was removed from the combined solutions on a flash evaporator,
and the residual oil was extracted with boiling petroleum ether (bp 60-80 C)
(2 100 mL), and then with diethyl ether (100 mL). The combined extracts were

washed with iced water (3

80 mL), dried over calcium chloride, and filtered. The
solvents were removed from the filtrate under reduced pressure to give 17.4 g of
an oil, which on distillation yielded 13.7 g (76%) of a clear liquid; bp 143 C (3.5
mmHg), which solidified in the receiver; mp 34-35 C.

Phosphoryl chloride
Another method for producing DCC from dicyclohexylurea is a two-step process
using phosphoryl chloride in dichloromethane at 40 C for 4 h under non-basic
conditions followed by removal of acidic components with aq. sodium hydroxide.
This method, which gives an 89% yield of DCC, has been presented in a patent
application [1256] (see Section 4.5.3.5, Table 4.48).

1. POCl 3
CH 2 Cl 2

O

N N

40°C, 4 h

H H

89 %
DCC

2. NaOH, H 2 O

1693

Triphenylphosphine dibromide
A general method for the synthesis of carbodiimides, isonitriles, ketimines, and
aldehydes using triphenylphosphine dibromide has been developed. Diphenyl and
dicyclohexyl carbodiimides are formed from N,N 0 -disubstituted ureas in the pres-
ence of triethylamine at 80 C in 90 min in yields of 66-75% [1257].
As already mentioned in Section 4.3.4.1, bis-4-(2,2-dimethyl-1,3-dioxolyl)methyl
carbodiimide (BDDC) 1034, a useful reagent for residue-free esterifications, race-
mization-free peptide couplings, and dehydrations, has been prepared in 89% yield
from the symmetrical urea 1033 by dehydration with triphenylphosphine dibro-
mide at room temperature [758].