Chemistry Reference
In-Depth Information
O
Ph
3
P, Br
2
N
C
N
O
N
H
N
H
O
O
O
O
O
O
O
Et
3
N
CH
2
Cl
2
rt, 3 h
89 %
BDDC
1034
1033
Typical procedure. Bis-4-(2,2-dimethyl-1,3-dioxolyl)methyl carbodiimide (BDDC) 1034
[758]:
Triphenylphosphine (131 g, 110 mol%) was dissolved in dry dichloro-
methane (1.1 L), and the resulting solution was cooled to 0
C. Bromine (25.7 mL,
80 g, 110 mol%) was added dropwise over a period of 15 min, and then triethyl-
amine (157 mL, 114 g, 250 mol%) was added in one portion. Solid urea 1033 (131
g, 0.45 mol) (for the preparation of 1033, see Section 4.3.4.1) was added to the yel-
low suspension in small portions over a period of 50 min. The resulting brown
slurry was stirred at room temperature for an additional 3 h, then diluted with
hexane (500 mL), and the solids were filtered off and washed with diethyl ether.
The solvents were evaporated from the combined filtrate and washings to leave a
brown slurry, which was resuspended in fresh diethyl ether and again diluted with
hexane. The solids were filtered off and washed with diethyl ether as before. This
procedure of evaporation, suspension, and filtration was repeated until no further
solids precipitated (usually four cycles). The final viscous, clear brown oil, crude
1034, was bulb-to-bulb distilled at reduced pressure to give pure BDDC 1034 (107 g,
89%) as a pale-yellow oil. It could be stored indefinitely at 0
C under argon; bp
115-125
C, 0.3 mmHg; IR: n
max
2130 cm
1
.
This procedure also gives a good example of the purification of carbodiimides.
Carbodiimides 1701-1703 and 1707 were each prepared in 52-56% yield by de-
hydrating the appropriate urea with triphenylphosphine dibromide. 1701 is used as
a peptide coupling reagent in an inverse Merrifield approach to peptide synthesis
[1258]. 1702 is applied in forming guanidines for enantiomerically pure guanidine-
catalyzed asymmetric nitroaldol reaction [1259]. 1703 is employed as an e
cient
sulfur-transfer agent based on N-acetylcysteine methyl ester 1704, forming a thia-
zole 1706 via intermediate 1705 [1260]. 1707 is an intermediate in a new synthesis
of ranitidine, in which a nitromethenylation at the carbodiimide carbon affords
1708 [1261].
ΒΌ
Triphenylphosphine/tetrahalomethanes
Appel applied the dehydration reagent triphenylphosphine/tetrachloromethane to
the synthesis of carbodiimides from ureas under extremely mild conditions, and
obtained yields of 87-92% [1262].
General procedure. Carbodiimides from ureas or thioureas [1262]:
Equimolar amounts
of urea or thiourea, tetrachloromethane, triethylamine, and triphenylphosphine (in
20% excess) are warmed to 40
C under stirring in dry dichloromethane. Within
1 h, the initial suspension (ureas are only sparingly soluble in dichloromethane) is
transformed into a clear, yellow-brown solution. After a further 1.5 h, most of the
resulting triethylammonium chloride has crystallized. The solvent is evaporated at
