Synthesis of guanidines from amines and carbodiimides catalyzed by mono-indenyl-ligated rare earth metal bis(silylamide) complexes

Article abstract of DOI:10.1002/cjoc.201300302

Nucleophilic addition of primary aromatic amines to carbodiimides in the presence of catalytic amount of the mono-indenyl-ligated rare earth metal bis(silylamide) complexes (C₉H₆CMe₂CH ₂C₅H₄N-α)Ln[N(SiHMe₂) ₂]₂ at room temperature afforded efficiently a series of guanidines with a wide spectrum of substituents on the nitrogen atoms. Nucleophilic addition of primary aromatic amines to carbodiimides promoted by the mono-indenyl-ligated rare earth metal bis(silylamide) complexes (C ₉H₆CMe₂CH₂C₅H ₄N-α)Ln[N(SiHMe₂)₂]₂ afforded a series of guanidines. Copyright

Full text of DOI:10.1002/cjoc.201300302

FULL PAPER
DOI: 10.1002/cjoc.201300302
Synthesis of Guanidines from Amines and Carbodiimides
Catalyzed by Mono-Indenyl-Ligated Rare Earth Metal
Bis(silylamide) Complexes
Jue Chen, Yibin Wang, and Yunjie Luo*
Organometallic Chemistry Laboratory, Ningbo Institute of Technology, Zhejiang University,
Ningbo, Zhejiang 315100, China
Nucleophilic addition of primary aromatic amines to carbodiimides in the presence of catalytic amount of the
mono-indenyl-ligated rare earth metal bis(silylamide) complexes (C H CMe CH C H N-α)Ln[N(SiHMe ) ] at
9
6
2
2
5
4
2 2 2
room temperature afforded efficiently a series of guanidines with a wide spectrum of substituents on the nitrogen
atoms.
Keywords rare earth, amide complex, amine, carbodiimide, guanylation, catalysis
Introduction
Experimental
Guanidines are important heteroatom-containing or-
ganic compounds which can serve as structural motifs
for biological and pharmaceutical compounds, and as
ancillary ligands in the coordination and organometallic
Materials and procedures
All manipulations were performed under pure argon
with rigorous exclusion of air and moisture using stan-
dard Schlenk techniques and an argon-filled glovebox.
Solvents (toluene, hexane, and THF) were distilled from
sodium/benzophenone ketyl, degassed by the freeze-
pump-thaw method, and dried over fresh Na chips in the
glovebox. All carbodiimides and amines were pre-
[
1]
chemistry. Addition of amine N－H bonds to car-
bodiimides (R-N＝C＝N-R) provides a straightforward
and atom-economical strategy to guanidines. However,
without a catalyst such reaction requires harsh condi-
[2]
tions. Recently, imide complexes of titanium and va-
treated before use. CDCl
CIL. (C CMe CH
3
and C
6
D
6
were obtained from
(Ln＝
[
3]
nadium, amide complexes of main metals, rare earth
9
H
6
2
2
C
5
H
4
N-α)Ln[N(SiHMe ) ]
2 2 2
[
4]
[
9b]
metals and titanium, alkyl complexes of half-sand-
Sc (1), Y (2), La (3), Sm (4), Nd (5), Er (6), Lu (7))
[5]
wich rare earth metal alkyl complexes, and commer-
were prepared according to the literature.
[
6]
1
13
2
cially available metal alkyl complexes such as ZnEt ,
NMR ( H, C) spectra were recorded on a Bruker
AVANCE III spectrometer at 25 ℃. Carbon, hydrogen,
and nitrogen analyses were performed by direct com-
bustion on a Carlo-Erba EA-1110 instrument, quoted
data are the average of at least two independent deter-
minations. FT-IR spectra were recorded on a Bruker
TENSOR 27 spectrometer.
[6]
[7]
[8]
n-BuLi, AlR
3
,
and Zn(OTf)
2
were found to be ef-
ficient catalysts for the addition of amines to carbodi-
imides to afford multi-substituted guanidines. Never-
theless, rare earth metal bis(amide) complexes as cata-
lysts for the guanylation reaction of amines and carbodi-
imides remains unexplored to our knowledge.
During our investigation on the structure-reactivity
relationship of rare earth metal complexes, we became
interested in exploiting rare earth metal bis(amide)
complexes as appropriately active catalyst precursors.
It was found that the half-sandwich rare earth metal
bis(silylamide) complexes bearing the pyridylfunction-
General procedures for synthesis of guanidines by
reaction of aromatic amines with carbodiimides
[9]
The procedures for catalytic reactions promoted by
these rare earth metal complexes were similar, and a
typical procedure is given below. A 50 mL Schlenk tube
was charged with 2 (10 mg, 0.005 mmol), N,N'-diiso-
propylcarbodiimide (0.42 g, 1 mmol), and aniline (0.31
g, 1 mmol), and 1 mL toluene in the glovebox. The re-
sulting mixture was stirred at 20 ℃ for 30 min. Then
the tube was taken out from the glovebox. The reaction
alized indenyl ligand (C
9
H
6
CMe
(Ln＝Sc (1), Y (2), La (3), Sm (4), Nd
5), Er (6), Lu (7)) were highly active catalysts in the
2 2 5 4
CH C H N-α)Ln-
[
(
2 2 2
N(SiHMe ) ]
guanylation of primary amines and carbodiimides. Here
we wish to report these results.
*
E-mail: lyj@nit.zju.edu.cn
Received April 12, 2013; accepted May 29, 2013; published online XXXX, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300302 or from the author.
Chin. J. Chem. 2013, XX, 1—7
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1

Chen, Wang & Luo
FULL PAPER
mixture was hydrolyzed by water (3.0 mL), extracted
N-p-Methoxyphenyl-N',N"-diisopropylguanidine
2 2 2 4
with CH Cl (15 mL×3), dried over anhydrous Na SO ,
and filtered. The filtrate was dried, and the residue was
purified by recrystallization from a mixture solution of
ether and hexane to afford a white solid.
MeO
N
NH
HN
N-Phenyl-N',N"-diisopropylguanidine
[
3a]
Known compound.
This compound was isolated
1
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.15 (d,
J＝6.0 Hz, 12H, NCHMe
NH was not observed), 3.75 (br s, 2H, NCHMe ), 3.77
3
N
NH
HN
2
), 3.52 (br s, 1H, NH, another
2
3
(s, 3H, OCH ), 6.75－6.83 (m, 4H, Ar-H).
[
4d]
N-p-Methoxyphenyl-N',N"-dicyclohexylguanidine
Known compound.
This compound was isolated
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.16 (d,
J＝6.4 Hz, 12H, CHMe ), 3.56 (br s, 2H, NH), 3.74－
), 6.85 (d, J＝7.2 Hz, 2H, Ph-H),
.92 (t, J＝7.2 Hz, 1H, Ph-H), 7.24 (t, J＝7.6 Hz, 2H,
1
3
MeO
N
Cy
NH
2
3
6
.79 (m, 2H, CHMe
2
Cy NH
[
3a]
Known compound.
This compound was isolated
) δ: 1.03－
Ph-H).
1
as a white solid. H NMR (400 MHz, CDCl
3
N-Phenyl-N',N"-dicyclohexylguanidine
1
1
.20 (m, 6H, Cy-H), 1.30－1.39 (m, 4H, Cy-H), 1.56－
.62 (m, 2H, Cy-H), 1.65－1.71 (m, 4H, Cy-H), 2.00 (d,
N
Cy
NH
J＝10.4 Hz, 4H, Cy-H), 3.40 (br s, 2H, Cy-H), 3.59 (br
3
s, 1H, NH), 3.77 (s, 3H, OCH ), 6.75－6.82 (m, 4H,
Cy NH
Ar-H).
[
4d]
Known compound.
This compound was isolated
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.04－
.21 (m, 6H, Cy-H), 1.29－1.42 (m, 4H, Cy-H), 1.57－
N-p-Chlorophenyl-N',N"-diisopropylguanidine
1
3
1
1
3
Cl
N
.71 (m, 6H, Cy-H), 2.00 (d, J＝9.2 Hz, 4H, Cy-H),
.41 (br s, 2H, Cy-H), 3.62 (br s, 1H, NH, another NH
NH
HN
was not observed), 6.85 (d, J＝7.6 Hz, 2H, Ph-H), 6.91
t, J＝7.6 Hz, 1H, Ph-H), 7.23 (t, J＝8.0 Hz, 2H, Ph-H).
(
[
3a]
Known compound.
This compound was isolated
) δ: 1.16 (d,
), 3.54 (br s, 2H, NH), 3.75 (sp,
), 6.78 (d, J＝8.8 Hz, 2H, Ar-H), 7.19 (d,
1
N-p-Methylphenyl-N',N"-diisopropylguanidine
as a white solid. H NMR (400 MHz, CDCl
J＝6.4 Hz, 12H, CHMe
2H, CHMe
3
2
N
NH
HN
2
J＝8.4 Hz, 2H, Ar-H).
N-p-Chlorophenyl-N',N"-dicyclohexylguanidine
[
4c]
Known compound.
This compound was isolated
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.15 (d,
J＝6.4 Hz, 12H, NCHMe ), 2.28 (s, 3H, Ar-CH ), 3.54
br s, 1H, NH, another NH was not observed), 3.76 (br s,
H, NCHMe ), 6.74 (d, J＝8.0 Hz, 2H, Ar-H), 7.04 (d,
Cl
N
Cy
NH
1
3
Cy NH
2
3
[
4c]
(
2
Known compound.
This compound was isolated
) δ: 1.03－
1
2
as a white solid. H NMR (400 MHz, CDCl
3
J＝8.0 Hz, 2H, Ar-H).
1.19 (m, 6H, Cy-H), 1.28－1.39 (m, 4H, Cy-H), 1.57－
1
2
2
.62 (m, 2H, Cy-H), 1.66－1.71 (m, 4H, Cy-H), 1.96－
.00 (m, 4H, Cy-H), 3.38 (br s, 2H, Cy-H), 3.60 (br s,
H, NH), 6.77 (d, J＝8.4 Hz, 2H, Ar-H), 7.18 (d, J＝8.8
N-p-Methylphenyl-N',N"-dicyclohexylguanidine
N
Cy
NH
Hz, 2H, Ar-H).
Cy NH
N-p-Nitrophenyl-N',N"-diisopropylguanidine
[
4c]
Known compound.
This compound was isolated
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.03－
.19 (m, 6H, Cy-H), 1.29－1.39 (m, 4H, Cy-H), 1.56－
.61 (m, 2H, Cy-H), 1.66－1.71 (m, 4H, Cy-H), 2.27 (s,
H, Ar-CH ), 3.40 (br s, 2H, Cy-H), 3.61 (br s, 1H, NH,
1
O N
N
3
2
NH
1
1
3
HN
3
[
4d]
another NH was not observed), 6.74 (d, J＝8.0 Hz, 2H,
Ar-H), 7.04 (d, J＝8.4 Hz, 2H, Ar-H).
Known compound.
This compound was isolated
) δ: 1.19 (d,
1
as a yellow solid. H NMR (400 MHz, CDCl
3
2
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Synthesis of Guanidines from Amines and Carbodiimides
J＝6.0 Hz, 12H, CHMe
2
), 3.76－3.80 (m, 4H), 6.89－
(t, J＝7.6 Hz, 1H, Ar-H), 7.07 (d, J＝7.6 Hz, 1H,
Ar-H).
6
.91 (m, 2H, Ar-H), 8.10－8.13 (m, 2H, Ar-H).
N-o-Methylphenyl-N',N"-diisopropylguanidine
N,N"-Dicyclohexyl-N'-2,6-diisopropylphenylguani-
dine
N
NH
HN
N
Cy
NH
[
4c]
Known compound.
This compound was isolated
HN
Cy
1
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.16 (d,
J＝6.4 Hz, 12H, CHMe ), 2.14 (s, 3H, Ar-CH ), 3.43
br s, 1H, NH, another NH was not observed), 3.76 (br s,
H, CHMe ), 6.76 (d, J＝8.0 Hz, 1H, Ar-H), 6.87 (dt,
3
[4c]
2
3
Known compound.
This compound was isolated
as a white solid. H NMR (400 MHz, CDCl ) δ: 0.81－
2.35 (m, 20H, Cy-H), 1.15 (d, J＝6.8 Hz, 12H, CHMe2),
1
(
2
3
2
J＝1.2, 7.2 Hz, 1H, Ar-H), 7.09 (t, J＝7.6 Hz, 1H,
Ar-H), 7.14 (d, J＝7.6 Hz, 1H, Ar-H).
3.08 (sept, 2H, CHMe ), 3.89 (br s, 1H, NH, another
NH was not observed), 6.95 (t, J＝7.6 Hz, 1H, Ar-H),
2
7
.06 (d, J＝7.6 Hz, 2H, Ar-H).
N-o-Methylphenyl-N',N"-dicyclohexylguanidine
1
,3-Diisopropyl-2-(pyridin-2-yl)guanidine
N
Cy
NH
N
Cy NH
N
NH
[
4c]
HN
Known compound.
This compound was isolated
1
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.02－
.18 (m, 6H, Cy-H), 1.29－1.39 (m, 4H, Cy-H), 1.57－
.62 (m, 2H, Cy-H), 1.66－1.70 (m, 4H, Cy-H), 2.01 (d,
3
1
1
[11]
Known compound.
This compound was isolated
) δ: 1. 25 (d,
), 3.93 (br s, 2H, CHMe ), 6.61
t, J＝5.6 Hz, 1H, Py-H), 6.83 (d, J＝8.4 Hz, 1H, Py-H),
.87－7.20 (br s, 1H, NH), 7.41 (dt, J＝2.2, 7.6 Hz, 1H,
Py-H), 8.07 (dd, J＝1.6, 5.2 Hz, 1H, Py-H).
1
as a white solid. H NMR (400 MHz, CDCl
J＝6.4 Hz, 12H, CHMe
3
J＝10.4 Hz, 4H, Cy-H), 2.13 (s, 3H, Ar-CH ), 3.40 (br s,
3
2
2
2
H, Cy-H), 3.48 (br s, 1H, NH, another NH was not
observed), 6.76 (d, J＝7.6 Hz, 1H, Ar-H), 6.86 (t, J＝
.6 Hz, 1H, Ar-H), 7.08 (t, J＝7.6 Hz, 1H, Ar-H), 7.13
d, J＝7.2 Hz, 1H, Ar-H).
(
6
7
(
1
,3-Dicyclohexyl-2-(pyridin-2-yl)guanidine
N,N'-Diisopropyl-N"-2,6-dimethylphenylguanidine
Cy
N
N
NH
N
NH
HN
Cy NH
[
12]
Known compound.
This compound was isolated
) δ: 1.24－
.32 (m, 6H, Cy-H), 1.35－1.45 (m, 4H, Cy-H), 1.58－
1
as a white solid. H NMR (400 MHz, CDCl
3
[3a]
1
1
2
6
(
1
Known compound.
This compound was isolated
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.16 (br
s, 12H, CHMe ), 2.10 (s, 6H, Ar-CH ), 3.32 (br s, 2H,
CHMe ), 3.96 (br s, 2H, NH), 6.79 (t, J＝7.6 Hz, 1H,
1
.63 (m, 2H, Cy-H), 1.71－1.77 (m, 4H, Cy-H), 1.98－
.03 (m, 4H, Cy-H), 3.61 (br s, 2H, Cy-H), 6.60 (t, J＝
.4 Hz, 1H, Py-H), 6.83 (d, J＝8.4 Hz, 1H, Py-H), 7.41
3
2
3
2
dt, J＝2.4, 4.0 Hz, 1H, Py-H), 8.06 (dd, J＝1.6, 5.2 Hz,
Ar-H), 6.99 (d, J＝7.6 Hz, 2H, Ar-H).
H, Py-H).
N,N"-Diisopropyl-N'-2,6-diisopropylphenylguanidine
1
,3-Diisopropyl-2-(pyrimidin-2-yl)guanidine
N
N
N
NH
N
HN
NH
HN
New compound. This compound was isolated as a
1
white solid. m.p. 127－128 ℃; H NMR (400 MHz,
CDCl ) δ: 1.24 (d, J＝6.4 Hz, 12H, NCHMe ), 4.05 (br
[
4c]
Known compound.
This compound was isolated
3
2
1
as a white solid. H NMR (400 MHz, CDCl ) δ: 1.15 (d,
J＝7.2 Hz, 12H, ArCHMe ), 1.15 (br s, 12H, NCHMe ),
.09 (sept, 2H, ArCHMe ), 3.40 (br s, 2H, NCHMe ),
.19 (br s, 1H, NH, another NH was not observed), 6.96
2
s, 2H, NCHMe ), 6.55 (t, J＝4.8 Hz, 1H, Py-H), 6.62－
3
1
3
2
2
7.23 (br s, 1H, NH), 8.38 (d, J＝4.8 Hz, 2H, Py-H). C
NMR (100 MHz, CDCl ) δ: 23.4 (CHMe ), 42.6
3
4
2
2
3
2
2
(CHMe ), 111.1 (Py-C), 155.2 (N＝CNH), 157.1 (Py-C),
Chin. J. Chem. 2013, XX, 1—7
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3

Chen, Wang & Luo
FULL PAPER
1
66.4 (Py-C). FT-IR (KBr) ν: 3350 (s), 3170 (s), 2780
Table 1 Reaction of aniline with N,N′-diisopropylcarbodiimide
a
(w), 2680 (w), 1650 (s), 1560 (s), 1480 (s), 1360 (m),
catalyzed by (C
9
H
6
CMe
2
CH
2
C
5
H
4
2 2 2
N-α)Ln[N(SiHMe ) ]
－
1
1
220 (w), 1180 (w), 802 (m) cm ; GC-MS (EI) m/z:
＋
C
11
H
19
N
5
221. Anal. calcd for C11
H
19
N
5
: C 59.70, H
N
cat.
N
8
.65, N 31.65; found C 59.64, H 8.61, N 31.75.
NH2
+
o
H N
H
N C N
20 C
1
,3-Dicyclohexyl-2-(pyrimidin-2-yl)guanidine
N
Catalyst loading/
mol%
Cy
N
Run cat.
t/min Isolated yield/%
N
NH
Cy NH
1
2
3
4
5
6
7
8
9
1
1 (Sc)
1 (Sc)
2 (Y)
2 (Y)
2 (Y)
2 (Y)
3 (La)
4 (Sm)
2
30
30
30
30
30
30
30
30
30
30
30
30
64
9
New compound. This compound was isolated as a
white solid. m.p. 125－126 ℃; H NMR (400 MHz,
CDCl ) δ: 1.23－1.32 (m, 6H, Cy-H), 1.37－1.47 (m,
H, Cy-H), 1.57－1.63 (m, 2H, Cy-H), 1.69－1.75 (m,
H, Cy-H), 1.98－2.03 (m, 4H, Cy-H), 3.74 (br s, 2H,
Cy-H), 6.54 (t, J＝4.4 Hz, 1H, Py-H), 8.38 (d, J＝4.8
0.5
2
1
99
99
99
92
62
95
35
53
84
71
3
1
4
4
0.5
0.2
0.5
2
1
3
Hz, 2H, Py-H). C NMR (100 MHz, CDCl ) δ: 24.6,
3
2
1
3
(
8
9
5.7, 33.5, 49.2 (Cy-C), 111.0 (Py-C), 155.2 (N＝CNH),
57.1 (Py-C), 166.5 (Py-C). FT-IR (KBr) ν: 3330 (s),
170 (s), 2930 (m), 2850 (m), 2780 (w), 2680 (w), 1650
s), 1560 (s), 1480 (s), 1360 (m), 1220 (w), 1180 (w),
04 (m) cm . Anal. calcd for C H N : C 67.73, H
17 27 5
4 (Sm) 0.5
5 (Nd) 0.5
0
11
6 (Er)
0.5
－
1
1
2
7 (Lu) 0.5
.03, N 23.24; found C 67.66, H 8.96, N 23.38.
a
The reaction was performed by treating 1 equiv. of aniline with
1
lyst.
equiv. of N,N′-diisopropylcarbodiimide with 1－7 as the cata-
Results and Discussion
The catalytic reaction of aniline PhNH
2
with
i
i
N,N′-diisopropylcarbodiimide PrN＝C＝N Pr was first
examined under various conditions. The results were
summarized in Table 1. It is noteworthy that, in the ab-
sence of (C H CMe CH C H N-α)Ln[N(SiHMe ) ]
2 2 2
9
6
2
2
5
4
(
Ln＝Sc (1), Y (2), La (3), Sm (4), Nd (5), Er (6), Lu
i
i
(7)), the reaction of PrN＝C＝N Pr with aniline did not
take place under the present conditions. In contrast, ad-
dition of a small amount (0.5 mol%) of 2 at 20 ℃ in-
duced rapidly the nucleophilic addition of aniline to
i
i
PrN＝C＝N Pr to afford quantitatively N,N',N"-trisub-
stituted guanidine in 30 min (Table 1, run 5). Even
when the catalyst loading decreased to 0.2 mol%, the
isolated yield still reached upon to 92% using 2 as the
catalyst (Table 1, run 6). The other mono-indenyl-
ligated rare earth metal bis(silylamide) complexes 1, 3
Figure
1
The comparison of catalytic activity using
(
C H CMe CH C H N-α)Ln[N(SiHMe ) ] as catalysts.
9 6 2 2 5 4 2 2 2
－
7 were also effective for this catalytic reaction. The
was hardly dependent on the electron-donating sub-
stituents at the phenyl ring (Table 2, runs 1－6). How-
ever, it was strongly influenced by the electron-
withdrawing substituents at the phenyl ring. For exam-
ple, the reaction of 4-nitrophenylamine with diisopro-
pylcarbodiimide at 20 ℃ for 24 h only gave 26% yield
catalytic activity is shown in Figure 1. Obviously,
among these rare earth metal catalysts, 2 exhibited the
highest activity. In contrast, 1 showed rather poor activ-
ity, only 9% isolated yield was obtained at the expense
of 0.5 mol% catalyst loading in 30 min (Table 1, run 2).
The catalytic activity of 2 was comparable with that by
[
10]
(
Table 2, run 9). In comparison, under the same condi-
tris(guanidinate) rare earth metal complexes.
tions the electron-donating group substituted aromatic
amines showed much higher activity than the elec-
tron-withdrawing substituted aromatic amines. This
finding is somewhat different to the results obtained
from tris(guanidinate) rare earth metal complexes, in-
which the reaction was not influenced by either elec-
tron-withdrawing or electron-donating substituents at
Therefore, 2 was chosen as the catalyst for the addi-
tion reaction of various primary aromatic amines with
carbodiimides. As shown in Table 2, a wide range of
substituted anilines could be applied for this reaction.
N,N′-diisopropylcarbodiimide PrN＝C＝N Pr and
N,N′-dicyclohexylcarbodiimide CyN＝C＝NCy showed
similar activity in these reactions. The catalytic reaction
i
i
4
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Synthesis of Guanidines from Amines and Carbodiimides
Table 2 Reactions of different aromatic and heterocyclic amines with carbodiimides catalyzed by (C
9
6
H CMe
2
CH
2
C
5
H
4
N-α)Ln-
a
[
N(SiHMe ) ] (2)
2 2 2
H
2
(0.5 mol%)
H
R
R1 NH2
N
N
R
+
R N C N R
N
R1
1
Run R –NH
R
T/˚C
t/h
Product
Isolated yield/%
99
2
N
i
NH
1
Pr 20
0.5
HN
NH2
Cy
NH
N
2
3
4
Cy 20
0.5
0.5
0.5
1
98
99
99
95
96
95
95
26
Cy NH
N
i
NH
Pr 20
HN
NH2
Cy
NH
N
Cy 20
Cy NH
MeO
N
i
NH
5
Pr 20
HN
MeO
NH2
Cy
NH
MeO
Cl
N
6
Cy 20
1
Cy NH
N
i
NH
7
Pr 20
1
HN
Cl
NH2
Cy
NH
Cl
N
8
Cy 20
1
Cy NH
O N
N
2
i
NH
9
1
O N
NH2
Pr 20
24
2
HN
N
i
0
Pr 20
4
7
NH
93
91
HN
NH2
Cy
NH
N
11
Cy 20
Cy NH
Chin. J. Chem. 2013, XX, 1—7
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

Chen, Wang & Luo
Continued
FULL PAPER
1
Run R -NH
R
T/℃
t/h
Product
Isolated yield/%
2
N
i
1
1
2
3
NH2
Pr 20
18
NH
91
HN
N
i
Pr 20 (80)
24
24
43 (91)
NH
HN
NH2
N
Cy
NH
1
4
Cy 20 (80)
32 (90)
HN
Cy
N
i
N
N
NH
1
1
1
5
6
7
8
Pr 20
3
95
92
95
97
HN
NH2
N
Cy
N
Cy 20
3
NH
Cy NH
N
N
i
N
NH
Pr 20
0.5
HN
N
N
NH2
N
N
Cy
NH
N
1
Cy 20
0.5
Cy NH
a
The reaction was performed by treating 1 equiv. of aromatic or heterocyclic amines with 1 equiv. of carbodiimides with 0.05 equiv. (10
mg) of 2 as the catalyst in toluene (1 mL).
[
10]
the phenyl ring. Meanwhile, the position and bulky of
the substituents at the phenyl ring also dramatically af-
fect the reactivity. In the case of 2,6-diisopropylphenyl
amine, the reaction with carbodiimides required a higher
temperature (80 ℃) and longer reaction time (24 h) for
ca. 90% isolated yield, probably due to the steric hin-
drance of isopropyl group (Table 2, runs 13 and 14).
Remarkably, aromatic C－Cl bond survived in the pre-
sent reaction (Table 2, runs 7 and 8), and heterocyclic
primary amines such as 2-pyridinyl amine and 2-pyrimi-
dinyl amine could also be used for this reaction.
cleophilic addition of the amide species (i) to a carbo-
diimide gave the mixed-ligated rare earth metal guani-
dinate species (ii). Protonation of ii by another molecule
of amine regenerated the rare earth metal amide com-
plex (i) with the release of the guanidine (iii). Rear-
rangement of iii through 1,3-hydrogen shift afforded the
more stable guanidine isomer.
Conclusions
In summary, nucleophilic addition of primary aro-
matic amines to carbodiimides took place efficiently in
the presence of catalytic amount of the mono-indenyl-
ligated rare earth metal bis(silylamide) complexes, and
afforded a series of guanidines with a wide spectrum of
A proposed mechanism for the present catalytic re-
action is illustrated in Scheme 1. Amide exchange of the
rare earth metal amide complex with an amine yielded
straightforwardly an aromatic amide species (i). Nu-
6
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, XX, 1—7

Synthesis of Guanidines from Amines and Carbodiimides
Scheme 1 Proposed mechanism for the guanylation reaction of
amines and carbodiimides
Cohen, B. D.; Koide, H., Plenum Press, New York, 1987; (c) Hu,
L.-Y.; Guo, J.; Magar, S. S.; Fischer, J. B.; Burke-Howise, K. J.;
Durant, G. J. J. Med. Chem. 1997, 40, 4281; (d) Manimala, J. C.;
Anslyn, E. V. Eur. J. Org. Chem. 2002, 67, 3909; (e) Trifonov, A. A.
Coord. Chem. Rev. 2010, 254, 1327; (f) Bailey, P. J.; Pace, S. Coord.
Chem. Rev. 2001, 214, 91.
Ln N(SiHMe2)2
R
R
N H
N H
ArNH2
Ar
N
[
2] (a) Tin, M. K. T.; Thirupathi, N.; Yap, G. P. A.; Richeson, D. S. J.
Chem. Soc., Dalton Trans. 1999, 2947; (b) Tin, M. K. T.; Thirupathi,
N.; Yap, G. P. A.; Richeson, D. S. Inorg. Chem. 1998, 37, 6728.
HN(SiHMe2)2
1
,3-H shift
[3] (a) Ong, T. G.; Yap, G. P. A.; Richeson, D. S. J. Am. Chem. Soc.
2003, 125, 8100; (b) Montilla, F.; Pastor, A.; Galindo, A. J. Or-
ganomet. Chem. 2004, 689, 993.
Ln NHAr
(i)
R
R
H
N
C
N
RN
NHAr
[
4] (a) Ong, T. G.; O’Brien, J. S.; Korobkov, I.; Richeson, D. S. Or-
ganometallics 2006, 25, 4728; (b) Zhou, S. L.; Wang, S.; Yang, G.;
Li, Q.; Zhang, L.; Yao, Z.; Zhou, Z.; Song, H. Organometallics 2007,
(iii)
N
R
R
2
6, 3755; (c) Li, Q.; Wang, S.; Zhou, S.; Yang, G.; Zhu, X.; Liu, Y.
ArNH2
J. Org. Chem. 2007, 72, 6763; (d) Shen, H.; Chan, H. S.; Xie, Z. W.
Organometallics 2006, 25, 5515.
Ln
NHAr
R
[5] (a) Zhang, W.; Nishiura, M.; Hou, Z. J. Am. Chem. Soc. 2005, 127,
16788; (b) Zhang, W.; Nishiura, M.; Hou, Z. Synlett 2006, 8, 1213;
=
Ligand (L)
(
ii)
(c) Zhang, W.; Nishiura, M.; Hou, Z. Chem. Eur. J. 2007, 13, 4037.
substituents on the nitrogen atoms. Among these rare
earth metal bis(amide) complexes, the yttrium species
showed the highest activity. The catalytic activity was
influenced by the electronic effect, the steric effect and
the position of the substituents at the phenyl ring.
[6] Alonso-Moreno, C.; Carrillo-Hermosilla, F.; Garcés, A.; Otero, A.;
López-Solera, I.; Rodríguez, A. M.; Antinolo, A. Organometallics
2
010, 29, 2789.
7] Zhang, W.-X.; Li, D.; Wang, Z.; Xi, Z. Organometallics 2009, 28,
82.
8] Li, D.; Guang, J.; Zhang, W.-X.; Wang, Y.; Xi, Z. Org. Biomol.
Chem. 2010, 8, 1816.
[
[
8
Acknowledgement
[9] (a) Luo, Y. J.; Lei, Y. L.; Fan, S. M.; Wang, Y. B.; Chen, J. Dalton
Trans. 2013, 42, 4040; (b) Wang, Y. B.; Lei, Y. L.; Chi, S. H.; Luo,
Y. J. Dalton Trans. 2013, 42, 1862; (c) Chen, F.; Fan, S. M.; Wang,
Y. B.; Chen, J.; Luo, Y. J. Organometallics 2012, 31, 3730; (d)
Wang, Y. B.; Luo, Y. J.; Chen, J.; Xue, H. M.; Liang, H. Z. New J.
Chem. 2012, 36, 933; (e) Luo, Y. J.; Feng, X. Y.; Wang, Y. B.; Fan,
S. M.; Lei, Y. L.; Liang, H. Z. Organometallics 2011, 30, 3270; (f)
Luo, Y. J.; Fan, S. M.; Yang, J. P.; Fang, J. H.; Xu, P. Dalton Trans.
2011, 40, 3053.
This work was partly financially supported by the
National Natural Science Foundation of China (No.
2
1172195).
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Chin. J. Chem. 2013, XX, 1—7
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
7