Copper(II) reagent-promoted degradation of N,N′-dialkyldiazenedicarboxamides

Article abstract of DOI:10.1246/bcsj.75.329

Degradation of N,N′-dialkyldiazenedicarboxamides with a copper(II) reagent, which was prepared from lithium 4-nitrophenoxide and copper(II) bromide in tetrahydrofuran, proceeded via formation of isocyanate to produce the corresponding 4-nitrophenyl N-alky

Full text of DOI:10.1246/bcsj.75.329

c. Jpn.
e Chemical © 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 329–333 (2002)
329
ciety of Ja-
n
e Chemical
ciety of Ja-
n
Copper(Ⅱ) Reagent-Promoted Degradation of
N,Nꢀ-dialkyldiazenedicarboxamides
Degradation of Dialkyldiazenedicarboxamides
J. Yamaguchi et al.
Jun-ichi Yamaguchi,* Yukihito Murayama, and Takayuki Suyama*
0
9
3
2
Department of Applied Chemistry, Faculty of Engineering, Kanagawa Institute of Technology,
Shimo-ogino, Atsugi, Kanagawa 243-0292
SJA8
09-2673
(
Received August 17, 2001)
2
0
0
78
Degradation of N,Nꢀ-dialkyldiazenedicarboxamides with a copper(Ⅱ) reagent, which was prepared from lithium 4-
1
1
nitrophenoxide and copper(Ⅱ) bromide in tetrahydrofuran, proceeded via formation of isocyanate to produce the corre-
sponding 4-nitrophenyl N-alkylcarbamate with the evolution of nitrogen. Further, it was also found that 4-nitrophenyl N-
alkylcarbamate reacted with primary or secondary amines to give the corresponding multisubstituted urea. Based on the
above results, we developed a new method for the one-pot preparation of multisubstituted ureas from N,Nꢀ-dialkyldiaz-
enedicarboxamides.
Previously, it was reported that a copper(Ⅱ) reagent 1a pre-
pared from lithium t-butoxide and copper(Ⅱ) bromide is useful
for oxidative transformation of substrates containing a hydro-
gen–nitrogen bond. For example, oxidative transformation of
1b prepared from lithium 4-nitrophenoxide and copper(Ⅱ) bro-
mide, which transformed N,Nꢀ-dialkyldiazenedicarboxamides
2 chemoselectively into 4-nitrophenyl N-alkylcarbamates 3
with the evolution of nitrogen (Scheme 1). The reagent 1b
showed tolerance to primary and secondary amines, and N-
substituted urea. We also report here the one-pot conversion of
2 into multisubstituted ureas 4 by treatment of the resulting
carbamate 3 with amines (Scheme 2).
1
2
3
amino groups, hydrazine derivatives, carboxamide, N-sub-
4
4
stituted urea, and N,Nꢀ-dialkyldiazenedicarboxamide with 1a
afforded imines, gem-dihalo compounds, t-butyl ester, and t-
butyl carbamate, respectively. Similarly, primary and second-
ary alcohols were oxidized with 1a to the corresponding car-
5
Results and Discussion
bonyl compounds.
Concerning the above transformation of functional groups
Initially, the preparation of several copper(Ⅱ) reagents from
lithium aryloxides and copper(Ⅱ) bromide was examined.
Since lithium 2-chlorophenoxide was brominated by treatment
of copper(Ⅱ) bromide to form 4-bromo-2-chlorophenol, the
preparation of a copper(Ⅱ) reagent from lithium 2-chlorophen-
oxide was unsuccessful. On the contrary, a copper(Ⅱ) reagent
1b prepared from lithium 4-nitrophenoxide and copper(Ⅱ) bro-
mide was stable in THF at room temperature.
using 1a, we assume that t-butoxide is a strong base, so that 1a
1–5
can react with many types of functional groups.
Therefore,
if a copper(Ⅱ) reagent is prepared from aryloxide instead of t-
butoxide, it will promote a chemoselective transformation.
Transformation of functional groups is a basic task in organic
synthesis, in which chemoselectivity is of special importance.
In the present study, we developed a new copper(Ⅱ) reagent
Scheme 1.
Scheme 2.

3
30 Bull. Chem. Soc. Jpn., 75, No. 2 (2002)
Degradation of Dialkyldiazenedicarboxamides
Scheme 3.
Scheme 4.
Next, we examined the oxidation of 2a with 1b in tetrahy-
Table 1. A One-Pot Preparation of N,N-Diethyl-Nꢀ-pheneth-
ylurea 4b
a)
drofuran (THF) at room temperature, and found that 4-nitro-
phenyl N-phenethylcarbamate 3a and N,Nꢀ-diphenethylurea 4a
were produced in 75% and 3% yields, respectively (Scheme 3).
The formation of 4a is due to a small amount of water which
existed in the reaction mixture. It is reasonable to assume that
the reaction of phenethyl isocyanate with water affords phen-
ethylamine and its addition to another isocyanate gives 4a. 4-
Nitrophenyl N-alkylcarbamate 3 as well as 4-nitrophenyl
Run Molar amounts of 1b Temperature Time/min Yield/%
1
2
3
4
5
4.0
2.1
3.2
4.0
5.2
RT
15
15
15
15
15
54
58
75
87
66
50 °C
50 °C
50 °C
50 °C
6
7
a) All reactions were carried out by method A except for
Run 1. See experimental section.
esters and carbonates are known as activated esters and react
with primary or secondary amines to give the corresponding
8
ureas. It was found that the reaction of 3a with diethylamine
in THF gave N,N-diethyl-Nꢀ-phenethylurea 4b in 72% yield
reactions proceeded to give 4 in high yields in most cases. The
yields apparently depend on the structures of 2 and the amine
used. Unfortunately, the corresponding ureas 4 were obtained
in low yield when an aromatic or a cyclic amine was employed
(Runs 6 and 7).
The probable reaction mechanism of the one-pot prepara-
tion of multisubsituted ureas is outlined in Scheme 5. In the
first step, the reaction of 2 with 1b produces the copper(Ⅱ)
amide 5, and the subsequent degradation of 5 gives isocyanate
6 with the evolution of nitrogen. Diels and Paquin have report-
ed a similar pyrolysis of N,Nꢀ-diethyldiazenedicarboxamide
(Scheme 4).
On the basis of these results, we next examined a one-pot
preparation of multisubstituted ureas 4b from 2a (Table 1).
Although the starting material 2a was consumed when the re-
action was performed at room temperature, the yield of 4b was
not satisfactory (Run 1). After several attempts, the yield of 4b
was improved when the reaction was performed at 50 °C, and
the order of addition of reagents was changed (Run 4).
The one-pot preparation of 4 from various 2 and amines was
carried out. The results listed in Table 2 show that the present
a)
Table 2. The One-Pot Preparation of 4
1
2
3
b)
c)
Run
R
R
R
Method
B
Time/min Compound Yield/%
1
2
3
4
5
Ph(CH
2
)
2
2a
PhCH
i-Pr
cyclohexyl
n-Bu
t-Bu
pyrrolidine
Ph
PhCH
PhCH
n-Bu
PhMeCH
PhCH
2
PhCH
i-Pr
H
H
H
2
15
20
20
20
20
25
25
20
20
20
20
25
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
92
84
90
86
80
49
34
66
86
80
90
83
d)
A
d)
A
d)
A
d)
A
e)
6
A
A
d)
7
8
9
Me
PhCH
PhCH
Me
H
PhCH
PhCH
cyclohexyl 2c
Ph(CH
2
2b
2
2
2
A
A
2
d)
10
11
12
2
)
3
2d
A
d)
A
4m
4n
n-Bu
2e
2
2
B
a) All reactions were performed at 50 °C except for Run 6. b) See experimental section. c) Isolated
yield of urea. d) Two molar amounts of amine were used. e) The reaction was carried out at room
temperature.

J. Yamaguchi et al.
Bull. Chem. Soc. Jpn., 75, No. 2 (2002) 331
Scheme 5.
16 4 2
128.39, 138.07, 161.82; Anal. Calcd for C16H N O : C, 64.85; H,
9
bis-silver salt to form ethyl isocyanate. Because t-butyl car-
bamate is produced by the addition of an alkoxycopper(Ⅱ) spe-
cies prepared from lithium t-butoxide and copper(Ⅱ) bromide
5.44; N, 18.91%. Found: C 64.21, H 5.68, N 18.57%.
N,Nꢀ-Dicyclohexyldiazenedicarboxamide (2c):
Yellow
4
3
crystals; mp 203–204 °C (decomp, EtOH); IR (KBr) 3255, 2932,
to isocyanate, it is speculated that 1b attacks isocyanate to af-
ford 4-nitrophenyl carbamate 3. Since alkaline hydrolysis or
2854, 1700 cm− ; H NMR (300 MHz, DMSO-d ) δ 1.05–1.35
1
1
1
0
6
11
(m, 10H), 1.50–1.90 (m, 10H), 3.56 (brs, 2H), 8.80 (d, J = 7.8 Hz,
H); C NMR (75 MHz, DMSO-d ) δ 24.40, 24.90, 31.94, 49.32,
60.63; Anal. Calcd for C14H N O : C, 59.98; H, 8.63; N,
aminolysis of 4-nitrophenyl N-substituted carbamate affords
the corresponding isocyanate, 6 will be regenerated by amino-
lysis of 3 under the present reaction conditions. In the last
step, the addition of amine to 6 gives multisubstituted urea 4 as
the final product.
In conclusion, we have found that the copper(Ⅱ) reagent 1b
is powerful enough to promote the degradation of N,Nꢀ-dial-
kyldiazenedicarboxamides 2 to isocyanate 6. This oxidative
transformation can be used for preparation of multisubstituted
ureas 4 from 2 and amines.
13
2
1
1
6
24 4 2
9.98%. Found: C 59.74, H 8.52, N 20.03%.
N,Nꢀ-Bis(3-phenylpropyl)diazenedicarboxamide (2d): Or-
ange crystals; mp 149.5–150.5 °C (decomp, EtOH); IR (KBr)
3
7
4
235, 1707 cm− ; H NMR (300 MHz, DMSO-d
1
1
6
) δ 1.96 (tt, J =
.3 and 7.3 Hz, 4H), 2.71 (t, J = 7.3 Hz, 4H), 3.42 (q, J = 7.3 Hz,
H), 7.10–7.30 (m, 10H), 8.54 (brs, 2H); C NMR (75 MHz,
13
DMSO-d
Anal. Calcd for C20
6
) δ 30.69, 32.78, 39.98, 125.78, 128.25, 141.22, 161.49;
: C, 68.16; H, 6.86; N, 15.90%.
24 4 2
H N O
Found: C 68.39, H 6.93, N 15.77%.
Experimental
N,Nꢀ-Dibutyldiazenedicarboxamide (2e): Orange crystals;
mp 158 °C (decomp, EtOH); IR (KBr) 3263, 1707 cm− ; H NMR
1 1
General. Melting points are uncorrected. IR spectra were
measured on a JASCO FT/IR 410 spectrometer. H NMR spectra
1
(300 MHz, DMSO-d ) δ 0.94 (t, J = 7.3 Hz, 6H), 1.39 (qt, J = 7.3
6
1
3
(
300 MHz) and C NMR spectra (75 MHz) were recorded on a
JEOL JMN-LA300 spectrometer using deuteriochloroform or
DMSO-d as a solvent with tetramethylsilane as an internal stan-
dard. Mass spectra were measured on a SHIMADZU GCMS-
QP1000A spectrometer, and high resolution mass spectra were
measured on a Hitachi M-80B spectrometer. Copper(Ⅱ) halide
was dried at 90–100 °C for several hours under reduced pressure.
The Preparation of N,Nꢀ-Dialkyldiazenedicarboxamides 2.
The following compounds were prepared according to the report-
and 7.3 Hz, 4H), 1.58 (tt, J = 7.3 and 7.3 Hz, 4H), 3.31 (td, J =
13
7.3 and 5.7 Hz, 4H), 8.69 (brt, J = 5.7 Hz, 2H); C NMR (75
6
MHz, DMSO-d ) δ 13.62, 19.74, 31.07, 40.10, 161.51; Anal. Cal-
6
cd for C H N O : C, 52.61; H, 8.83; N, 24.54%. Found: C
10
20
4
2
52.43, H 8.59, N 24.79%.
A Preparation of Lithium 4-Nitrophenoxide.
4-Nitrophe-
nol was added to a solution of an equimolar amount of lithium hy-
droxide monohydrate. After being stirred for several minutes, the
reaction mixture was condensed under reduced pressure, followed
by removal of a small amount of water as azeotrope using toluene.
The residue was reprecipitated with THF and diethyl ether. The
yellow precipitate was collected by filtration with suction, and
then was dried at 140 °C for 5 h.
1
2
ed method.
N,Nꢀ-Diphenethyldiazenedicarboxamide (2a):
Orange
crystals; mp 148–149 °C (decomp, EtOH); IR (KBr) 3329, 1716
4
−
1 1
cm ; H NMR (300 MHz, DMSO-d
.47 (td, J = 7.1 and 5.4 Hz, 4H), 7.18–7.33 (m, 10H), 8.95 (brt,
6
) δ 2.85 (t, J = 7.1 Hz, 4H),
3
Orange crystals; mp > 300 °C; IR (KBr) 3613, 3581, 1587,
1
3
−1 1
J = 5.4 Hz, 2H); C NMR (75 MHz, DMSO-d
26.36, 128.43, 128.70, 138.54, 161.19; Anal. Calcd for
: C, 66.65; H, 6.21; N, 17.27%. Found: C 66.56, H
6
) δ 35.09, 41.88,
1329 cm ; H NMR (300 MHz, DMSO-d ) δ 6.29 (d, J = 7.3 Hz,
6
1
C
5
2H), 7.88 (d, J = 7.3 Hz, 2H).
18
H
20
N
4
O
2
Treatment of 2a with 1b. To a THF solution (3.0 mL) of
lithium 4-nitorophenoxide (218 mg, 1.50 mmol) was added cop-
per(Ⅱ) bromide (335 mg, 1.50 mmol) at room temperature under
nitrogen, and the reaction mixture was stirred for 15 min. N,Nꢀ-
Diphenethyldiazenedicarboxamide (2a) (81 mg, 0.25 mmol) was
added to the reaction mixture. After the mixture had been stirred
.96, N 17.40%.
N,Nꢀ-Dibenzyldiazenedicarboxamide (2b):
Orange crys-
tals; mp 188–189 °C (decomp, EtOH:DMF = 1:1 by volume);
IR (KBr) 3238, 1709 cm− ; H NMR (300 MHz, DMSO-d
1
1
) δ
6
4
.44 (d, J = 5.8 Hz, 4H), 7.27–7.38 (m, 10H), 9.38 (brt, J = 5.8
1
3
6
Hz, 2H); C NMR (75 MHz, DMSO-d ) δ 43.44, 127.19, 127.43,
for 3 h, the reaction was quenched by addition of saturated NH Cl
4

3
32 Bull. Chem. Soc. Jpn., 75, No. 2 (2002)
Degradation of Dialkyldiazenedicarboxamides
1
1
solution (15 mL) and a small amount of 7.5% aqueous NH
tion. The organic materials were extracted with EtOAc (30 mL).
3
solu-
(KBr) 3359, 1619, 1536 cm− ; H NMR (300 MHz, CDCl
3
) δ 1.15
(d, J = 6.8 Hz, 12H), 2.85 (t, J = 6.8 Hz, 2H), 3.51 (q, J = 6.8
Hz, 2H), 3.82 (sept, J = 6.8 Hz, 2H), 4.14 (brs, 1H), 7.19–7.33
(m, 5H); C NMR (75 MHz, CDCl
−
3
The organic layer was washed with 0.25 M (1 M = 1 mol dm
Na CO solution (50 mL, 4 times) and water (50 mL, 5 times) suc-
cessively, and was dried over Na SO . After removal of the sol-
)
13
2
3
3
) δ 21.24, 36.13, 41.73, 44.82,
+
2
4
126.30, 128.50, 128.88, 139.61, 157.14; MS (EI) m/z 248 (M ),
+
vent under reduced pressure, the residue was purified by prepara-
tive TLC (silica gel, hexane:EtOAc = 4:1) and 3a (108 mg) and
N,Nꢀ-diphenethylurea 4a (4 mg) were obtained in 75% and 3%
yields, respectively.
91 (C
248.1929.
N-Cyclohexyl-Nꢀ-phenethylurea (4e): Mp 117.5–119 °C;
7 7 24 2
H ); HRMS (EI): calcd for C15H N O 248.1889, found
IR (KBr) 2930, 2853, 1627, 1580 cm− ; H NMR (300 MHz,
CDCl ) δ 0.99–1.18 (m, 5H), 1.56–1.71 (m, 3H), 1.86–1.90 (m,
2H), 2.81 (t, J = 6.8 Hz, 2H), 3.40–3.48 (m, 3H), 4.15 (brs, 1H),
1
1
4
-Nitrophenyl Phenethylcarbamate (3a): Mp 104–105 °C;
3
−
1 1
IR (KBr) 3348, 1710, 1542 cm ; H NMR (300 MHz, CDCl
3
) δ
13
2
7
.91 (t, J = 6.8 Hz, 2H), 3.57 (q, J = 6.8 Hz, 2H), 5.15 (brs, 1H),
3
4.26 (brs, 1H), 7.18–7.33 (m, 5H); C NMR (75 MHz, CDCl ) δ
24.93, 25.59, 33.91, 36.40, 41.69, 49.20, 77.23, 126.43, 128.60,
128.86, 139.25, 157.39; MS (EI) m/z 246 (M ), 83 (C
1
3
.22–7.35 (m, 7H), 8.23 (d, J = 9.3 Hz, 2H); C NMR (75 MHz,
) δ 35.71, 42.35, 121.88, 125.04, 126.73, 128.72, 128.73,
38.13, 144.65, 153.00, 155.86; MS (EI) m/z 147
+
+
CDCl
1
3
6
H
11 ), 56
+
(C
4
H
8
); HRMS (EI): calcd for C15
H
22
N
2
O 246.1732, found
+
+
(
2
Ph(CH
2
)
2
NCO ), 91 (C
86.0953, found 286.0986.
N,Nꢀ-Diphenethylurea (4a): Mp 110–111 °C; IR (KBr)
7
H
7
); HRMS (EI): calcd for C15
H
14
N
2
O
246.1766.
N-Butyl-Nꢀ-phenethylurea (4f): Mp 70–71 °C; IR (KBr)
3344, 1619, 1577 cm− ; H NMR (300 MHz, CDCl
) δ 0.90 (t, J
1
1
3
1
1
3
427, 1655 cm− ; H NMR (300 MHz, CDCl
3
) δ 2.83 (t, J = 6.8
= 7.1 Hz, 3H), 1.23–1.48 (m, 4H), 2.79 (t, J = 6.8 Hz, 2H), 3.10
(q, J = 7.1 Hz, 2H), 3.42 (q, J = 6.8 Hz, 2H), 4.49 (brs, 1H), 4.54
(brs, 1H), 7.17–7.32 (m, 5H); C NMR (75 MHz, CDCl
13.79, 20.02, 32.31, 36.47, 40.24, 41.66, 126.38, 128.56, 128.82,
Hz, 4H), 3.45 (t, J = 6.8 Hz, 4H), 4.62 (brs, 2H), 7.19–7.34 (m,
1
3
13
1
1
1
2
0H) ; C NMR (75 MHz, CDCl
3
) δ 36.14, 41.79, 126.52,
3
) δ
+
28.66, 128.84, 138.93, 158.23; MS (EI) m/z 164 (M −C
8
H
8
),
+
+
+
+
03 (C
68.1575, found 268.1608.
One-Pot Preparations of Multisubstituted Ureas 4. Meth-
od A: to a THF solution (4.0 mL) of lithium 4-nitorophenoxide
117 mg, 0.80 mmol) was added copper(Ⅱ) bromide (179 mg, 0.80
8
H
8
), 91 (C
7
H
7
); HRMS (EI): calcd for C17
H
20
N
2
O
139.26, 158.26; MS (EI) m/z 220 (M ), 91 (C
calcd for C13 O 220.1575, found 220.1604.
N-t-Butyl-Nꢀ-phenethylurea (4g): Mp 70–71 °C; IR (KBr)
7 7
H ); HRMS (EI):
20 2
H N
3355, 1632, 1573 cm− ; H NMR (300 MHz, CDCl
1 1
3
) δ 1.29 (s,
(
9H), 2.78 (t, J = 6.8 Hz, 2H), 3.37 (t, J = 6.8 Hz, 2H), 4.21 (brs,
2H), 7.17–7.31 (m, 5H); C NMR (75 MHz, CDCl
13
mmol) at room temperature under nitrogen, and the reaction mix-
ture was stirred for 15 min. After the resulting black solution was
heated to 50 °C, amine (0.40 mmol), and subsequently 2 (0.20
mmol) was added to the solution. The reaction was quenched by
3
) δ 29.55,
36.57, 41.48, 50.18, 126.30, 128.53, 128.82, 139.39, 157.75; MS
+
+
(EI) m/z 220 (M ), 91 (C
220.1575, found 220.1590.
N-Phenethyl-1-pyrrolidinecarboxamide (4h): Mp 84–85
7 7 20 2
H ); HRMS (EI): calcd for C13H N O
addition of saturated NH
of 7.5% NH solution. The organic materials were extracted with
EtOAc (30 mL). The organic layer was washed with 0.25 M
Na CO solution (50 mL, 4 times) and water (50 mL, 5 times) suc-
cessively, and was dried over Na SO . After removal of the sol-
vent under reduced pressure, the residue was purified by prepara-
tive TLC (silica gel, CHCl :MeOH = 9:1 by volume) and urea 4
4
Cl solution (15 mL) and a small amount
°C; IR (neat) 3332, 1631, 1538 cm−
CDCl ) δ 1.84–1.90 (m, 4H), 2.83 (t, J = 7.1 Hz, 2H), 3.24–3.29
(m, 4H), 3.50 (t, J = 7.1 Hz, 2H), 4.22 (brs, 1H), 7.19–7.33 (m,
1
; H NMR (300 MHz,
1
3
3
2
3
13
2
4
5H) ; C NMR (75 MHz, CDCl
126.31, 128.54, 128.85, 139.51, 156.76; MS (EI) m/z 218 (M ),
3
) δ 25.54, 36.63, 41.80, 45.10,
+
+
3
98 (C
found 218.1436.
N-Methyl-Nꢀ-phenethyl-N-phenylurea (4i): Oil; IR (neat)
5 8 18 2
H NO ); HRMS (EI): calcd for C13H N O 218.1419,
was isolated. Method B: to a THF solution (4.0 mL) of lithium 4-
nitorophenoxide (117 mg, 0.80 mmol) was added copper(Ⅱ) bro-
mide (179 mg, 0.80 mmol) at room temperature under nitrogen,
and the reaction mixture was stirred for 15 min. After the result-
ing black solution was heated to 50 °C, 2 (0.20 mmol) and subse-
quently amine (0.40 mmol) was added to the solution. The reac-
1652, 1518 cm− ; H NMR (300 MHz, CDCl
1 1
) δ 2.74 (t, J = 7.1
3
Hz, 2H), 3.22 (s, 3H), 3.43 (t, J = 7.1 Hz, 2H), 4.32 (brs, 1H),
7.07–7.37 (m, 10H); C NMR (75 MHz, CDCl ) δ 36.26, 37.05,
42.00, 126.24, 127.20, 127.30, 128.46, 128.77, 129.91, 139.27,
13
3
+
+
tion was quenched by addition of saturated NH
mL) and a small amount of 7.5% aqueous NH
4
Cl solution (15
solution. The
143.29, 157.13; MS (EI) m/z 254 (M ), 134 (C
8 8
H NO ), 91
+
3
(C
7
H
7
); HRMS (EI): calcd for C16
H
18
N
2
O 254.1419, found
work-up and purification described as above gave urea 4.
N,N-Diethyl-Nꢀ-phenethylurea (4b): Oil; IR (neat) 3349,
254.1473.
N,N-Dibenzyl-Nꢀ-cyclohexylurea (4j): Mp 138.5–139.5 °C;
1
626, 1534 cm− ; H NMR (300 MHz, CDCl
1
1
3
) δ 1.06 (t, J = 7.1
IR (KBr) 3319, 2932, 1607, 1546 cm ; H NMR (300 MHz,
CDCl ) δ 0.89–1.04 (m, 3H), 1.25–1.33 (m, 2H), 1.51–1.54 (m,
3H), 1.81–1.84 (m, 2H), 3.66–3.72 (m, 1H), 4.22 (d, J = 7.5 Hz,
−1
1
Hz, 6H), 2.83 (t, J = 6.8 Hz, 2H), 3.19 (q, J = 7.1 Hz, 4H), 3.49
3
1
3
(
(
1
q, J = 6.8 Hz, 2H), 4.31 (brs, 1H), 7.19–7.33 (m, 5H); C NMR
75 MHz, CDCl ) δ 13.72, 36.36, 41.26, 42.00, 126.33, 128.55,
28.88, 139.54, 157.12; MS (EI) m/z 220 (M ), 100 (C
HRMS (EI): calcd for C13 O 220.1575, found 220.1579.
N,N-Dibenzyl-Nꢀ-phenethylurea (4c): Mp 100.5–102.5 °C;
13
3
1H), 4.47 (s, 4H), 7.22–7.35 (m, 10H); C NMR (75 MHz,
CDCl ) δ 24.72, 25.57, 33.62, 49.33, 50.35, 127.27, 127.42,
128.74, 137.84, 157.79; MS (EI) m/z 322 (M ), 106 (C
+
+
5
H
10NO );
3
+
+
H N
20 2
7 8
H
N ), 91
+
(C
322.2058.
N,N,Nꢀ-Tribenzylurea (4k): Mp 115.5–117 °C (lit. 119–
7
H ); HRMS (EI): calcd for C21H N O 322.2045, found
7
2
6
2
IR (KBr) 3357, 1610, 1537 cm− ; H NMR (300 MHz, CDCl
1
1
) δ
.73 (t, J = 6.8 Hz, 2H), 3.48 (q, J = 6.8 Hz, 2H), 4.42 (s, 5H),
3
13
2
7
5
1
1
3
−1 1
.01–7.33 (m, 15H); C NMR (75 MHz, CDCl
0.25, 126.24, 127.17, 127.42, 128.51, 128.73, 128.77, 137.57,
3
) δ 36.27, 42.09,
120 °C); IR (KBr) 3353, 1620, 1537 cm ; H NMR (300 MHz,
CDCl ) δ 4.42 (d, J = 5.6 Hz, 2H), 4.52 (s, 4H), 4.71 (brt, J = 5.6
Hz, 1H), 7.09–7.36 (m, 15H); C NMR (75 MHz, CDCl
3
+
+
13
39.20, 158.38; MS (EI) m/z 344 (M ), 91 (C
O 344.1889, found 344.1937.
N,N-Diisopropyl-Nꢀ-phenethylurea (4d): Mp 77–79 °C; IR
7
H
7
); HRMS (EI):
3
) δ
calcd for C23
H
24
N
2
44.95, 50.34, 127.05, 128.22, 127.47, 128.45, 128.78, 137.52,
139.33, 158.32; MS (EI) m/z 330 (M ).
+

J. Yamaguchi et al.
Bull. Chem. Soc. Jpn., 75, No. 2 (2002) 333
N-Butyl-N-methyl-Nꢀ-(3-phenylpropyl)urea (4l):
Oil; IR
Chem. Lett., 1992, 1933. Oxidation of amino acid: T. Takeda, S.
Yamauchi, and T. Fujiwara, Synthesis, 1996, 600.
neat) 3343, 2929, 1628, 1539 cm− ; H NMR (300 MHz, CDCl
1
1
)
(
3
δ 0.92 (t, J = 7.3 Hz, 3H), 1.29 (tq, J = 7.3 and 7.3 Hz, 2H), 1.44
tq, J = 7.3 and 7.3 Hz, 2H), 1.85 (tt, J = 7.3 and 7.3 Hz, 2H),
2
Oxidation of hydrazone: T. Takeda, R. Sasaki, A.
(
Nakamura, S. Yamauchi, and T. Fujiwara, Synlett, 1996, 273; T.
Takeda, R. Sasaki, S. Yamauchi, and T. Fujiwara, Tetrahedron, 53,
557 (1997). Oxidation of hydrazide; J. Yamaguchi, T.Aoyagi, R.
Fujikura, and T. Suyama, Chem. Lett., 2001, 466.
3
1273.
4
2
.66 (t, J = 7.3 Hz, 2H), 2.77 (s, 3H), 3.18 (t, J = 7.3 Hz, 2H),
13
3
.28 (q, J = 7.3 Hz, 2H), 4.37 (brs, 1H), 7.14–7.29 (m, 5H);
) δ 13.79, 19.94, 30.09, 31.85, 33.43,
3.99, 40.58, 48.41, 125.74, 128.27, 128.30, 141.83, 157.92; MS
C
NMR (75 MHz, CDCl
3
3
J. Yamaguchi, K. Hoshi, and T. Takeda, Chem. Lett., 1993,
+
+
+
(
EI) m/z 248 (M ), 91 (C
O 248.1889, found 248.1903.
N-(1-Phenylethyl)-Nꢀ-(3-phenylpropyl)urea (4m): Oil; IR
7 7 4 9
H ), 57 (C H ); HRMS (EI): calcd for
15 24 2
C H N
J. Yamaguchi, T. Shusa, and T. Suyama, Tetrahedron Lett.,
40, 8251 (1999).
1 1
(
(
7
neat) 3333, 1631, 1568 cm− ; H NMR (300 MHz, CDCl
d, J = 7.1 Hz, 3H), 1.71 (tt, J = 7.8 and 7.8 Hz, 2H), 2.50 (t, J =
.8 Hz, 2H), 3.12 (dt, J = 7.8 Hz, 2H), 4.48 (brs, 1H), 4.72 (dq,
J = 7.1 Hz, 1H), 4.85 (brd, J = 7.1 Hz, 1H), 7.07–7.33 (m, 10H);
3
) δ 1.42
5
J. Yamaguchi, S. Yamamoto, and T. Takeda, Chem. Lett.,
1992, 1185.
6
M. Bodanszky, Nature, 175, 685 (1955); M. Bodanszky
and V. du Vigneaud, J. Am. Chem. Soc., 81, 5688 (1959).
13
C NMR (75 MHz, CDCl
3
) δ 23.52, 31.72, 33.02, 39.90, 50.36,
7
K. Hoste, D. Bruneel, A. D. Marre, F. D. Schrijver, and E.
1
25.86, 127.35, 128.33, 128.39, 128.77, 141,56, 144.19, 157.72;
Schacht, Macromol. Rapid Commun., 15, 697 (1994); D. M. Dixit
and C. C. Leznoff, J. Chem. Soc., Chem. Commun., 1977, 798.
+
+
MS (EI) m/z 282 (M ), 106 (C
O 282.1732, found 282.1741.
N,N-Dibenzyl-Nꢀ-butylurea (4n): Mp 86–87 °C; IR (neat)
8
H10 ); HRMS (EI): calcd for
C
H N
18 22 2
8
N. Choy, K. Y. Moon, C. Park, Y. C. Son, W. H. Jung, H.-i.
Choy, C. S. Lee, C. R. Kim, and H. Yoon, Org. Prep. Proc., 28,
173 (1996); B. Raji, J. M. Kassir, and T. P. Kogan, Bioorg. Med.
Chem. Lett., 8, 3043 (1998); Q. Liu, N. W. Luedtke, and Y. Tor,
Tetrahedron Lett., 42, 1445 (2001).
1
1
3
353, 2957, 2871, 1625, 1539 cm− ; H NMR (300 MHz, CDCl
3
)
δ 0.83 (t, J = 7.3 Hz, 3H), 1.16 (tq, J = 7.3 and 7.3 Hz, 2H), 1.36
(
1
tt, J = 7.3 and 7.3 Hz, 2H), 3.20 (q, J = 7.3 Hz, 2H), 4.41 (brs,
1
3
H), 4.48 (brs, 4H), 7.22–7.36 (m, 10H); C NMR (75 MHz,
) δ 13.74, 19.88, 32.18, 40.68, 50.30, 127.21, 127.41,
9
O. Diels and M. Paquin, Ber. Dtsch. Chem. Ges., 46, 2000
CDCl
28.75, 137.77, 158.55; MS (EI) m/z 296 (M ), 106 (C
3
(1913).
+
+
1
7
H
8
N );
10 H. L. Bender and R. B. Homer, J. Org. Chem., 30, 3975
(1965).
24 2
HRMS (EI): calcd for C19H N O 296.1889, found 296.1909.
1
1
F. M. Menger and L. E. Glass, J. Org. Chem., 39, 2469
(
1974).
1
2
E. E. Smissman and A. Makriyannis, J. Org. Chem., 38,
References
1
652 (1973).
1
Oxidation of amino group: J. Yamaguchi and T. Takeda,
13 H. Hammerich, Ber. Dtsch. Chem. Ges., 25, 1819 (1892).