Chemistry Reference
In-Depth Information
Although both of these methods offer some advantages over the previous ones and
are able to produce a variety of unsymmetrical substituted ureas without the use of
gas-phase or highly toxic reagents, they share a major drawback in that they gen-
erate large amounts of waste salts.
4.3.4.10
Catalytic [Ru(PPh
3
)
3
] Aminolysis of Formamides
In a more convenient and more environmentally friendly protocol, unsymmetrical
N,N
0
-disubstituted ureas, including sterically hindered ones, can be synthesized
(76-93% yield) from N-aryl-substituted formamides and amines in the presence of
catalytic amounts of Ru(PPh
3
)
3
(substrate/catalyst ratio 20:1) [736]. A catalytic cycle
involving the formation of an isocyanate-coordinated ruthenium dihydride inter-
mediate is postulated.
4.3.4.11
HY Zeolite HSZ-360 Catalyzed Aminolysis of Acetoacetanilides
A commercially available acid zeolite has also been reported to be an e
cient cat-
alyst in the completely salt-free production of ureas. Reaction of aromatic amines
with ethyl acetoacetate 1105 in the presence of HY zeolite HSZ-360 (1 g of zeolite/
20 mmol of amine) under solvent-free conditions gives symmetrical diarylureas
1107 in good yields (58-77%) and with excellent selectivity (93-96%) through a
straightforward procedure (route A). Acetone, ethanol, and traces of acetoacetani-
lides are the sole by-products [793].
This type of synthesis cannot be applied to aliphatic amines because these com-
pounds undergo nucleophilic attack at the keto group to produce b-alkylaminocro-
tonic acid ethyl esters as the main products.
However, symmetrical aliphatic ureas 1108 can be successfully prepared (65-
95% yield) by reacting primary aliphatic amines with acetoacetanilide 1106 over
the same zeolite catalyst (route B) (Table 4.35) [794].
H
H
ArNH
2
Y-Zeolite
(58-77 %)
NN
Ar
NH
2
Ar
H
N
route A
O
EtO
1107
OO
OO
1105
H
H
RNH
2
(65-95 %)
1106
N
N
Y-Zeolite
R
R
route B
O
1108
Ar = 4-MeOC
6
H
4
, C
6
H
5
,
3-MeC
6
H
4
, 4-MeC
6
H
4
, 4-ClC
6
H
4
R = alkyl, cycloalkyl
In both cases, the zeolite catalyst can be recovered and reused for at least five runs
without a discernible decrease in its activity.
General procedure. N,N
0
-Dialkylureas 1108 [794]: To a solution of the selected ali-
phatic amine (20 mmol) and zeolite HSZ-360 (0.5 g) at 180
C, the acetoacetanilide
(0.9 g, 5 mmol) was added portionwise. After 3 h, the reaction mixture was cooled
to room temperature, hot methanol (50 mL) was added, and the catalyst was re-
moved by filtration and washed with hot methanol (50 mL). After cooling the
combined methanol solutions to room temperature, the N,N
0
-dialkylurea 1108 was
