An efficient method for the enamination of 1,3-dicarbonyl compounds with ceric ammonium nitrate (CAN)

Article abstract of DOI:10.1002/jccs.200700127

An efficient method for the enamination of 1,3-dicarbonyl compounds by employing ceric ammonium nitrate (CAN) as the catalyst has been described. A variety of β-amino-α,β-unsaturated ketones and esters have been synthesized in excellent yield within a short reaction time under solvent-free conditions.

Full text of DOI:10.1002/jccs.200700127

Journal of the Chinese Chemical Society, 2007, 54, 879-884
879
An Efficient Method for the Enamination of 1,3-Dicarbonyl Compounds
with Ceric Ammonium Nitrate (CAN)
a
a
b
Li-Ping Mo * (
The College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050016, P. R. China
), Shu-Fen Liu (
) and Wan-Zhi Li (
)
a
b
Handan Research Institute of Chemical Industry, Handan 056002, P. R. China
An efficient method for the enamination of 1,3-dicarbonyl compounds by employing ceric ammo-
nium nitrate (CAN) as the catalyst has been described. A variety of b-amino-a,b-unsaturated ketones and
esters have been synthesized in excellent yield within a short reaction time under solvent-free conditions.
Keywords: Ceric ammonium nitrate; Enamination; 1,3-Dicarbonyl compounds; Solvent free.
2
4
INTRODUCTION
The enamination of 1,3-dicarbonyl compounds to
protection of benzylic tetrahydropyranyl ethers, direct
2
5
thiocyanation of enolisable ketones, and nitration of phe-
2
6
nol, cresol, and anisole. The unique catalytic feature of
CAN is very different from a conventional acidic catalyst.
Recently, it has also been utilized to catalyze the synthesis
yield b-amino-a,b-unsaturated ketones or esters is a useful
transformation in organic synthesis and consequently has
received considerable attention in recent years. A variety of
2
7
28
of b-keto enol ethers, 3,3-di(heteroaryl)indolin-2-one
1
2
3
4
29
catalysts such as HCl, H
2
SO
4
, p-TSA, HAc, trimethyl-
and 1,5-benzodiazepine derivatives. This prompted us to
explore further applications of CAN as a Lewis acid cata-
lyst in organic synthesis. Herein, we wish to describe the
enamination of 1,3-dicarbonyl compounds to prepare b-
amino-a,b-unsaturated ketones and esters under solvent-
free conditions using a catalytic amount of CAN (Scheme
I).
5
silyl trifluoromethanesulfonate (TMSTf), montmorillo-
6
7
8
9
nite K10, BF
3
·OEt
·7H
2
, silica gel, CoCl
2
·6H
2
O, Zn(ClO
4
)
2
·
1
0
11
12
13
6
H
2
O, CeCl
3
2
O, NaAuCl
4
,
Bi(OTf)
3
,
sulfated
1
4
15
zirconia and natural clays have been used to promote
this transformation. However, these methodologies suffer
from some drawbacks such as long reaction times, the use
of large amounts of costly catalysts, the low yields of the
desired products and the requirement of high tempera-
tures. Therefore, introduction of a new and efficient method
for the enamination of 1,3-dicarbonyl compounds is desir-
able.
Scheme I
In the past few years, ceric ammonium nitrate (CAN)
has been exploited extensively as an inexpensive and easily
available catalyst for various organic reactions such as oxi-
dation, oxidative free-radical reactions, nitration, carbon-
1
6
carbon bond formation, etc. Last year, it was used as an
efficient reagent for the synthesis of unsymmetrical bis-
RESULTS AND DISCUSSION
1
7
(
indolyl)alkanes, dihydrofuran-fused [60] fullerene de-
1
8
19
rivatives and conjugated nitro-olefins, esterification-
The reactions were first carried out using a 1:1 mole
ratio of 4-bromoaniline and ethyl acetoacetate in a round-
bottom flask with stirring under ambient conditions for 8 h
without adding any catalyst under solvent-free conditions.
The result showed more than 90% of 4-bromoaniline was
nitration of ortho-hydroxyphenyl carboxylic acids and
2
0
21
benzoic acids, oxidation of phenols, the addition of
2
2
azide to cinnamic ester, the protection and deprotection of
2
3
4
-oxo-4H-1-benzopyran-3-carbaldehydes, oxidative de-
*
Corresponding author. E-mail: moliping@126.com

8
80 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mo et al.
recovered. It was observed that the reaction proceeded effi-
ciently in the presence of CAN (1 mol%), giving ethyl 3-
and (4) has good substrate generality.
(
4-bromophenylamino) but-2-enoate in 82% yield (Table
, entry 16) under the same reaction conditions. Lower cat-
1
EXPERIMENTAL SECTION
alyst loading can also be used with only a slight drop in re-
action rate.
Melting points were recorded on an X-4 apparatus
Encouraged by this success, we extended the reaction
of 1,3-dicarbonyl compounds 1 with a wide range of amines
under similar conditions. A variety of primary, benzylic
and aromatic amines reacted with acetylacetone effectively
to afford the corresponding b-enaminone in good to excel-
lent yields (Table 1). It has been observed that the substi-
tuent properties of the aniline have an effect toward the
dicarbonyls on the rate and yield. Anilines containing elec-
tron-withdrawing groups, such as 4-chloroaniline afforded
the corresponding b-enamino ketone in 80% yield after 3 h
and are uncorrected. IR spectra were recorded using a Bio-
1
Rad FTS 135 spectrophotometer. H NMR (300 MHz) and
1
3
C NMR (75 MHz) spectra were recorded on a Bruker
spectrometer using TMS as internal standard. Mass spectra
were performed on a ThermoFinnigan LCQ Advantage in-
strument with an ESI source. The elemental analyses were
carried out in an Elemental Vario EL analyzer.
A Typical Procedure for the Enamination of 1,3-
Dicarbonyl Compounds
(
Table 1, entry 6), which showed an obvious electronic ef-
In a 25 mL round-bottom flask, equimolar amounts
of amine (5 mmol) and 1,3-dicarbonyl compounds along
with the catalyst (0.05 mmol) were placed. The mixture
was stirred at room temperature for the specified time (Ta-
ble 1). After completion of the reaction, the product was ex-
tracted with ethyl acetate (3 ´ 10 mL) and washed with
brine solution. The combined organic phases were dried
over anhydrous sodium sulfate and concentrated under
vacuum. The crude product thus was purified by column
chromatography on silica gel using ethyl acetate-n-hexane
(2:8 v/v).
fect. It should be pointed out that in the reaction of 1-benzo-
ylacetone with amines the regioselective amination of the
aliphatic carbonyl group (Table 1, entries 7 and 8) was ob-
served.
Also, this protocol can be extended for the prepara-
tion of b-amino-a,b-unsaturated esters. Linear (Table 1,
entries 9-17) and cyclic (Table 1, entries 18-20) b-keto-
esters were treated with a wide range of amines such as
aliphatic, cyclic and aromatic amines under the same reac-
tion conditions. In all cases, the reactions proceeded rap-
idly and smoothly at room temperature in comparison with
other methods; the products were obtained in excellent
yields and chemoselectivity to afford Z-b-enaminones,
(Z)-Ethyl 3-(cyclopropylamino)but-2-enoate (entry 10)
Yellowish oil. IR (neat) nmax 3291, 3089, 2980, 2901,
1687, 1654, 1609, 1491, 1439, 1339, 1267, 1160, 1062,
1
confirmed by H NMR spectrum of the products. It is note-
-
1 1
worthy that in the case of 1,3-diaminopropane, 2 equiv of
ethyl acetoacetate was used giving products with two
enamino ester groups (Table 1, entry 17). Moreover, the op-
tically active amine was converted into the corresponding
b-ketoesters without any racemization or inversion by
measuring its optical rotation and comparing with the liter-
ature values (Table 1, entry 20).
3
1027, 902, 785 cm ; H NMR (CDCl ) d 0.55-0.61 (m,
2H), 0.70-0.77 (m, 2H), 1.23 (t, J = 7.2 Hz, 3H), 2.05 (s,
3H), 2.52-2.60 (m, 1H), 4.07 (q, J = 7.2 Hz, 2H), 4.48 (s,
1
3
1H), 8.54 (br s, 1H, NH) ppm; C NMR (CDCl
3
, 75 MHz)
d 7.6, 14.5, 19.7, 24.6, 58.2, 82.6, 163.5, 170.3; ESI-MS:
+
9 2
170 (M+1) ; Anal. Calcd for C H15NO : C, 63.88; H, 8.93;
N, 8.28; Found: C, 64.06; H, 8.82; N, 8.50.
In conclusion, we have developed a facile and effi-
cient procedure for the enamination of 1,3-dicarbonyl com-
pounds using a catalytic amount of CAN at room tempera-
ture. The present method has the following advantages
compared to those reported in the previous literature: (1) it
is fast and efficient, employs a cheap, non-toxic CAN as
catalyst; (2) has a simple workup procedure and high yield
of products; (3) takes place under solvent-free conditions;
(Z)-Methyl 3-(cyclopropylamino)but-2-enoate (entry 11)
Yellowish oil. IR (neat) nmax 3521, 3294, 3006, 2948,
1691, 1655, 1608, 1493, 1339, 1269, 1163, 1062, 930, 785
-1 1
cm ; H NMR (CDCl
3
) d 0.56-0.61 (m, 2H), 0.71-0.77 (m,
2H), 2.05 (s, 3H), 2.52-2.60 (m, 1H), 3.60 (s, 3H), 4.48 (s,
1
3
1H), 8.53 (br s, 1H, NH) ppm; C NMR (CDCl
3
, 75 MHz) d
+
7.5, 19.7, 24.5, 49.7, 82.2, 163.6, 170.6; ESI-MS: 156 (M+1) ;

Enamination of 1,3-Dicarbonyl Compounds
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 881
Table 1. CAN mediated the enamination of 1,3-dicarbonyl compounds
1
,3-Dicarbonyl
Compounds
Time
(min)
Yield
(%)
Entry
1
Amines
Products
NH(CH ) CH
3
a
O
O
O
2
3
NH2
15
20
94
95
O
O
O
NHCH CH=CH2
2
2
3
CH2=CHCH2NH2
NH2
O
O
O
O
O
NH
15
12
94
95
O
NH
OMe
4
5
MeO
NH2
MeO
NH
Me
O
O
O
O
O
15
93
NH2
Ph
O
NH
Cl
6
7
Cl
NH2
360
60
80
83
O
O
O
O
NH
NH2
Ph
Ph
Ph
Ph
MeO
NH
OMe
O
O
8
9
100
88
NH2
NH(CH ) CH
2
3
3
O
O
O
O
O
18
10
96
95
NH2
OEt
OEt
OEt
NH
NH
O
O
1
0
NH2
OEt
O
O
O
1
1
1
2
NH2
10
15
93
93
OMe
OMe
OMe
O
O
NHCH CH
2 2
CH CH NH
2 2 2
MeO

8
82 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mo et al.
O
O
O
O
O
NHCH CH
2
2
1
1
1
3
4
5
CH CH NH
2 2
15
60
50
94
92
94
2
OMe
OEt
MeO
O
O
NH
NH2
EtO
O
O
O
O
NH
Me
Br
Me
Br
NH2
OEt
OEt
OEt
EtO
EtO
O
O
O
NH
1
1
6
7
NH2
360
25
82
NH
NH
O
O
b
92
H N
2
NH2
EtO
OEt
O
H
N
1
1
8
9
0
NH2
80
70
45
93
O
O
O
O
O
O
O
O
H
N
Me
MeO
NH2
95
92
O
O
O
O
NH
2
2
H2N
O
O
O
O
NH
O
1
2
NH2
90
91
95
OEt
OEt
O
O
EtO
NH
O
2
EtO
NH2
100
OEt
OEt
a
b
Isolated yield. 2 Equiv of ethyl acetoacetate (with respect to ethane-1,2-diamine) was used.

Enamination of 1,3-Dicarbonyl Compounds
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 883
+
Anal. Calcd for C
8
H
13NO
2
: C, 61.91; H, 8.44; N, 9.03;
123.0, 129.1, 140.6, 160.2, 168.5; ESI-MS: 232 (M+1) ;
Found: C, 61.71; H, 8.20; N, 9.25.
2
Anal. Calcd for C14H17NO : C, 72.70; H, 7.41; N, 6.06;
Found: C, 72.52; H, 7.18; N, 6.30.
(
Z)-Methyl 3-(phenethylamino)but-2-enoate (entry 12)
Yellowish oil. IR (neat) nmax 3289, 3021, 2945, 2864,
1
652, 1603, 1498, 1441, 1287, 1265, 1170, 1114, 932, 751
ACKNOWLEDGMENT
-1 1
cm . H NMR (CDCl
3
) d 1.82 (s, 3H), 2.84 (t, J = 7.2 Hz,
2
7
7
1
H), 3.45 (q, J = 7.2 Hz, 2H), 3.61 (s, 3H), 4.42 (s, 1H),
We thank the Science Foundation of Hebei Normal
University for financial support of this project.
1
3
.28-7.33 (m, 5H), 8.65 (br s, 1H, NH); C NMR (CDCl
5 MHz) d 19.7, 37.7, 45.2, 50.5, 82.3, 127.0, 129.1, 129.2,
39.0, 162.2, 171.2; Anal. Calcd for C13 : C, 71.21;
3
,
H
17NO
2
H, 7.81; N, 6.39; Found: C, 71.48; H, 8.02; N, 6.18.
Received February 9, 2006.
(
Z)-Ethyl 3-(4-bromophenylamino)but-2-enoate (entry
1
6)
REFERENCES
Pale yellow solid; mp 50-51 ºC. IR (KBr) nmax 3275,
977, 1646, 1609, 1579, 1479, 1384, 1260, 1168, 1063, 853,
1
2
3
. Coffey, S.; Thomson, J. K.; Wilson, F. J. J. Chem. Soc. 1936,
856.
. Martin, D. F.; Janusonis, G. A.; Martin, B. B. J. Am. Chem.
Soc. 1961, 83, 73.
. (a) Šimûnek, P.; Pešková, M.; Bertolasi, V.; LyCka, A.;
MacháCek, V. Eur. J. Org. Chem. 2004, 5055. (b) Furukawa,
M.; Okawara, T.; Noguchi, Y.; Terawaki, Y. Chem. Pharm.
Bull. 1979, 27, 2223.
. Adams, D.; Dominguez, J.; Lo Russo, V.; De Rekowski, N.
M. Gazz. Chim. Ital. 1989, 119, 281.
. Cartaya-Marin, C. P.; Henderson, D. G.; Soeder, R. W.
Synth. Commun. 1997, 27, 4275.
. (a) Braibante, M. E. F.; Braibante, H. S.; Missio, L.;
Andricopulo, A. Synthesis 1994, 898. (b) Braibante, H. T. S.;
Braibante, M. E. F.; Rosso, G. B.; Oriques, D. A. J. Braz.
2
7
1
-1 1
89, 546 cm ; H NMR (CDCl
.98 (s, 3H), 4.15 (q, J = 7.2 Hz, 2H), 4.71 (s, 1H), 6.95 (d, J
8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 10.35 (br s, 1H, NH)
3
) d 1.28 (t, J = 7.2 Hz, 3H),
=
1
3
ppm; C NMR (CDCl
3
, 75 MHz) d 14.5, 20.2, 58.9, 117.9,
1
3
4
25.7, 132.1, 138.6, 162.3, 170.3; ESI-MS (negative mode):
-
2
82 (M-1) ; Anal. Calcd for C12H14BrNO : C, 50.72; H,
4
5
6
.97; N, 4.93; Found: C, 50.45; H, 5.10; N, 5.05.
3
-(1-((R)-1-Phenylethylamino)ethylidene)-dihydrofuran-
(3H)-one (entry 20)
2
[
30]
Pale yellow solid, mp 72-74 ºC (Lit. mp 71-73 ºC);
20
[30]
20
[
a] : -508 (c 1.05, EtOH) (Lit. [a] : -506); IR (KBr):
D D
n = 3436, 3055, 2958, 1687, 1608, 1479, 1444, 1408, 1371,
Chem. Soc. 2003, 14, 994.
. $Stefane, B.; Polanc, S. Synlett 2004, 698.
. Gao, Y.-H.; Zhang, Q.-H.; Xu, J.-X. Synth. Commun. 2004,
-
1
1
7
8
1
1
4
5
6
1
3
223, 1099, 1021, 768 cm ; H NMR (CDCl , 300 MHz): d
.51 (d, J = 6.6 Hz, 3H), 1.78 (s, 3H), 2.80 (t, J = 6.6 Hz, 2H),
.27 (t, J = 6.6 Hz, 2H), 4.57-4.67 (m, 1H), 7.22-7.36 (m,
3
4, 909.
9
1
. Zhang, Z.-H.; Hu, J.-Y. J. Braz. Chem. Soc. 2006, 17, 1447.
0. Bartoli, G.; Bosco, M.; Locatelli, M.; Marcantoni, E.;
Melchiorre, P.; Sambri, L. Synlett 2004, 239.
1. Khodaei, M. M.; Khosropour, A. R.; Kookhazadeh, M.
1
3
3
H), 8.63 (br s, 1H, NH); C NMR (CDCl , 75 MHz): d
.8, 24.7, 26.4, 52.9, 65.2, 86.2, 125.5, 127.2, 128.8, 145.1,
+
56.4, 174.0; ESI-MS: 232 (M+1) ; Anal. Calcd for
1
C
14
H
17NO
2
: C, 72.70; H, 7.41; N, 6.06; Found: C, 72.90; H,
Synlett 2004, 1980.
12. Arcadi, A.; Bianchi, G.; Di Giuseppe, S.; Marinelli, F. Green
Chem. 2003, 5, 64.
7
.58; N, 5.88.
1
3. Khosropour, A. R.; Khodaei, M. M.; Kookhazadeh, M. Tet-
rahedron Lett. 2004, 45, 1725.
Ethyl 2-(phenylamino)cyclopent-1-enecarboxylate (en-
try 21)
1
1
4. Zhang, Z.-H.; Song, L.-M. J. Chem. Res. 2005, 817.
5. Silva, F. C.; De Souza, M. C. B. V.; Ferreira, V. F.; Sabino, S.
J.; Antunes, O. A. C. Catal. Commun. 2004, 5, 151.
Yellowish oil. IR (neat) nmax 3284, 2956, 1655, 1623,
-
1 1
1
503, 1479, 1263, 1171, 1048, 753 cm ; H NMR (CDCl
3
) d
1
.31 (t, J = 7.2 Hz, 3H), 1.83-1.92 (m, 2H), 2.57 (t, J = 7.2
16. (a) Dhakshinamoorthy, A. Synlett 2005, 3014. (b) Molander,
G. A. Chem. Rev. 1992, 92, 29. (c) Nair, V.; Panicker, S. B.;
Nair, L. G.; George, T. G.; Augustine, A. Synlett 2003, 156.
Hz, 2H), 2.80 (t, J = 7.2 Hz, 2H), 4.22 (q, J = 7.2 Hz, 2H),
1
3
7
.03-7.30 (m, 5H), 9.60 (br s, 1H, NH) ppm; C NMR
(
d) Sommermann, T. Synlett 1999, 834.
(
CDCl , 75 MHz) d 14.5, 21.6, 28.6, 33.5, 59.0, 97.6, 120.5,
3

8
84 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mo et al.
1
1
1
2
2
2
2
7. Zeng, X.-F.; Ji, S.-J.; Wang, S.-Y. Tetrahedron 2005, 61,
M. S. Indian J. Chem. 2005, 44B, 2409.
24. Heravi, M. M.; Kazemian, P.; Oskooie, H. A.; Ghassemzadeh,
M. J. Chem. Res. 2005, 105.
25. Kumar, A.; Pathak, S. R. Lett. Org. Chem. 2005, 2, 745.
26. Perez, C.; Perez-Gutierrez, S.; Gomez, S. A.; Zavala, M. A.
Org. Prep. Proced. Int. 2005, 37, 387.
27. Banerjee, B.; Mandal, S. K.; Roy, S. C. Chem. Lett. 2006, 35,
16.
28. Wang, S.Y.; Ji, S. J. Tetrahedron 2006, 62, 1527.
29. Varala, R.; Enugala, R.; Nuvula, S.; Adapa, S. R. Synlett
2006, 1009.
30. Zhang, Z.-H.; Yin, L.; Wang, Y.-M. Adv. Synth. Catal. 2006,
348, 184.
1
0235.
8. Cheng, X.; Wang, G.-W.; Murata, Y.; Komatsu, K. Chin.
Chem. Lett. 2005, 16, 1327.
9. Rao, A. S.; Srinivas, P. V.; Babu, K. S.; Rao, J. M. Tetrahe-
dron Lett. 2005, 46, 18141.
0. Pan, W.-B.; Wei, L.-M.; Wei, L.-L.; Wu, C.-C.; Wu, Y.-C. J.
Chin. Chem. Soc. 2005, 52, 173.
1. Pan, W.-B.; Wei, L.-M.; Wei, L.-L.; Wu, C.-C.; Chang, F.-R.;
Wu, Y.-C. J. Chin. Chem. Soc. 2005, 52, 581.
2. Chang, M.-Y.; Lin, C.-Y.; Sun, P.-P. J. Chin. Chem. Soc.
2
005, 52, 1061.
3. Shindalkar, S. S.; Madje, B. R.; Hangarge, R. V.; Shingare,