Highly Efficient Mechanochemical Reactions of 1,3-Dicarbonyl Compounds with Chalcones and Azachalcones Catalyzed by Potassium Carbonate

Article abstract of DOI:10.1055/s-2003-43350

Under the high-speed vibration milling conditions, K₂0CO ₃ was found to be a very efficient catalyst for the solvent-free Michael reactions of 1,3-dicarbonyl compounds with chalcones and azachalcones. In most cases, conventional side

Full text of DOI:10.1055/s-2003-43350

LETTER
61
Highly Efficient Mechanochemical Reactions of 1,3-Dicarbonyl Compounds
with Chalcones and Azachalcones Catalyzed by Potassium Carbonate
Efficient
M
echa
e
nochemical Reac
Z
tions of 1,3-Dic
h
arbonyl
C
om
a
pounds ng,a Ya-Wei Dong,a Guan-Wu Wang,*a Koichi Komatsub
a
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
Fax +86(551)3607864; E-mail: gwang@ustc.edu.cn
b
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611, Japan
Received 19 September 2003
problems, one of the best methods is to carry out this kind
of reaction under solvent-free condition, which has the
advantages of reduced pollution, low cost, and simplicity
in process and handling.6,7
Abstract: Under the high-speed vibration milling conditions,
K2CO3 was found to be a very efficient catalyst for the solvent-free
Michael reactions of 1,3-dicarbonyl compounds with chalcones and
azachalcones. In most cases, conventional side reactions were
avoided and thus excellent yields were achieved. The influences of
other catalysts and the vibration frequency on the Michael reaction
were investigated.
Recently a technique called ‘high-speed vibration mill-
ing’ (abbreviated as HSVM) has been successfully uti-
lized to promote solvent-free mechanochemical reactions
of fullerenes.8–15 However, there has been no report on
non-fullerene mechanochemical reaction under the
HSVM conditions. Herein, we wish to report our study on
the application of the HSVM technique to the solvent-free
reactions of 1,3-dicarbonyl compounds with chalcones
and azachalcones catalyzed by K2CO3. To the best of our
knowledge, we are not aware of any report on solvent-free
Michael reaction in the presence of catalytic amount of
K2CO3 and without any other catalyst.
Key words: Michael addition, chalcone, azachalcone, potassium
carbonate, mechanochemical reaction
The highly useful C–C bond formation through Michael
addition of 1,3-dicarbonyl compounds to a,b-unsaturated
ketones is frequently catalyzed by strong bases such as
NaOH, KOH, Ba(OH)2 and NaOEt. But these drastic con-
ditions often cause some side reactions, including rear-
rangement, bis-addition, auto-condensation, subsequent
condensation, retro Michael reaction and so on.1 These
undesirable side reactions decrease the yield and make the
purification of the products very difficult. It has been
pointed out that better results are obtained with weaker
bases such as piperidine, tertiary amines, or quaternary
ammonium hydroxides.2 There have been reports on
Michael reactions catalyzed by K2CO3 in organic sol-
vent,3 in water and in the presence of surfactant,4 and un-
der phase transfer catalysis conditions.5 To some extent,
these mild conditions can minimize the reversibility of the
Michael addition reaction6 and other side reactions, thus
improved yields can be achieved. However, there were
still some disadvantages due to long reaction time or te-
dious work-up in these methods. To circumvent the above
The Michael reactions of chalcones and azachalcones
with diethyl malonate were first examined and were found
to proceed efficiently in excellent yields at ambient tem-
perature in short reaction time under our HSVM condi-
tions (Scheme 1).
All solvent-free reactions were performed using a high-
speed vibration mill that consists of a capsule and a mill-
ing ball made of stainless steel.9b The capsule containing
the milling ball was fixed on a vibration arm of a home-
built mill, and was vibrated vigorously at a rate of 3500
rounds per minute. The solvent-free mechanochemical re-
action of chalcone 1 with equimolar amount of diethyl
malonate 2 in the presence of K2CO3 under the HSVM
conditions afforded essentially pure product 3 after
O
CO2Et
O
EtO2C
K2CO3 (10% equiv.)
HSVM
R
CH2(COOEt)2
+
X
R
X
1
2
3
X= CH, N; R = H, 4-CH3, 4-OCH3, 4-NO2, 3-NO2, 4-CN, 4-Cl, 3,4-Cl, 3,4-(OCH2O)-
Scheme 1
SYNLETT 2004, No. 1, pp 0061–0064
0
5.
0
1.
2
0
0
4
Advanced online publication: 26.11.2003
DOI: 10.1055/s-2003-43350; Art ID: U18903ST
© Georg Thieme Verlag Stuttgart · New York

62
Z. Zhang et al.
LETTER
washing the reaction mixture with water in most cases.16 second-order reaction rate resulting from ultimately high
This protocol does not require the use of any organic sol- concentrations of reactants with no use of solvent. Fur-
vent during the reaction process and only 10% molar thermore, in the HSVM technique, the high mechanical
equivalent of K2CO3 is enough to promote the reaction energy caused by local high pressure, friction, shear
efficiently. The yield and reaction time for the Michael strain, etc. can greatly enforce the reaction.14
addition of diethyl malonate 2 to various chalcones and
azachalcones 1 are summarized in Table 1.
To investigate the effect of the applied base on this Micha-
el reaction, we performed the reaction of 4-chlorochal-
cone (0.1 mmol) with ethyl acetoacetate (0.1 mmol)
(Scheme 2) in the presence of several different catalysts.
The results are summarized in Table 2.
Table 1 Michael Addition of Diethyl Malonate to Chalcones and
Azachalcones Catalyzed by K2CO3 under the HSVM Conditions
1a
Prod-
Reaction Yieldd
time (min)c (%)
uct 3b
+
ArCH=CHCOPh
CH3COCH2COOEt
R
X
1a
1b
1c
1d
1e
1f
H
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
3a
3b
3c
3d
3e
3f
55
50
60
35
10
15
50
30
60
25
30
30
60
30
25
98
98
91
99
99
99
99
99
76
99
99
99
92
99
98
4-CH3
4-OCH3
4-NO2
3-NO2
4-CN
Ph
Ar
ArCHCH2COPh
Ar
Ph
OH
+
+
CH
EtOOC
EtOOC
COCH3
EtOOC
O
O
Ar = 4-Cl-C6H4
1g
1h
1i
4-Cl
3g
3h
3i
4
5
6
3,4-Cl
3,4-OCH2O-
4-NO2
3-NO2
4-CN
Scheme 2
1j
3j
Table 2 Michael Reaction of 4-Chlorochalcone with Ethyl Ace-
toacetate in the Presence of Different Catalysts under the HSVM
Conditions
1k
1l
N
3k
3l
N
Entry Catalyst (equiv)
Reaction Product (yielda)
time (min)
1m
1n
1o
4-Cl
N
3m
3n
3o
1
2
3
4
5
6
7
None
40
40
60
60
60
60
60
4 (28%)
3,4-Cl
3,4-OCH2O-
N
K2CO3 (0.1)
Na2CO3 (0.1)
Na2CO3 (1.0)
KF/Al2O3b (0.1)
KF/Al2O3b (1.0)
NaOH (0.1)
4 (99%)
N
a Prepared according to our recently reported method.17
4 (47%)
b Characterized by mp, IR, 1H NMR, 13C NMR and HRMS spectral
4 (68%)
data.
c Time needed for the reaction to complete and the maximum reaction
time is limited to 1 h.
4 (28%) + 5 (17%)
4 (46%) + 5 (24%)
d Isolated yield from three runs.
4 (26%) + 5 (44%) + 6
As shown in Table 1, the Michael addition reactions gen-
erally gave products 3 in remarkably high yields, which
are almost quantitative. This protocol can be extended to
the Michael addition of other 1,3-dicarbonyl compounds
such as ethyl acetoacetate to chalcones and azachalcones
with quantitative yield in almost all cases. Compared with
existing methods, the main advantages of the present pro-
cedure are milder condition, higher yield, shorter reaction
time and occurrence of no side reactions. For example,
compound 4 was previously prepared in 85% yield which
was catalyzed by activated Ba(OH)2 in EtOH at room tem-
perature for 8 h,1c whereas under our solvent-free HSVM
conditions, it was obtained in 99% yield at room temper-
ature for 40 min. The reasons for the efficiency of the cur-
rent solvent-free procedure may be due to an enhanced
(23%)
8
NaOH (1.0)
60
4 (trace) + 5 (57%) + 6
(32%)
a Isolated by column chromatography.
b 40 wt% KF, prepared according to reported method.18
From Table 3 we can see that, in this reaction system, ba-
sic catalyst is necessary to make it proceed practically.
Weaker catalysts such as Na2CO3 and K2CO3 have higher
product selectivity, affording only Michael adduct 4. Be-
tween these two catalysts, K2CO3 promoted the reaction
much more efficiently. When the Michael reaction was
catalyzed by strong bases such as KF/Al2O3 and NaOH,
further aldol condensation and subsequent dehydration
Synlett 2004, No. 1, 61–64 © Thieme Stuttgart · New York

LETTER
Efficient Mechanochemical Reactions of 1,3-Dicarbonyl Compounds
63
occurred to afford compounds 5 and 6. It is obvious that
K2CO3 is the best catalyst for the Michael reaction under
the HSVM conditions in term of yield and selectivity.
References
(1) (a) Bergman, E. D.; Ginsberg, D.; Rappo, R. Org. React.
1959, 10, 179. (b) Davey, W.; Gwilt, J. R. J. Chem. Soc.
1957, 1015. (c) Garcia-Raso, A.; Garcia-Raso, J.;
To further explore this reaction system, we have carried
out the Michael reaction under different vibration fre-
quencies. It was found that the vibration frequency of the
applied vibration mill had a significant effect on the
Michael reaction (Table 3).
Campaner, B.; Mestres, R.; Sinisterra, J. V. Synthesis 1982,
1037. (d) Ganesh, S.; Sarkar, A. Tetrahedron Lett. 1991, 32,
1085. (e) Li, T.-L.; Cui, Y.; Chen, G.-F.; Cheng, Z.-L.; Li,
T.-S. Synth. Commun. 2003, 33, 353.
(2) House, H. O. In Modern Synthetic Reactions, 2nd ed.;
Benjamin, W. A., Ed.; Amsterdam: New York, 1972, 595.
(3) Rosnati, V.; Saba, A.; Salimbeni, A. Tetrahedron Lett. 1981,
22, 167.
Table 3 Michael Reaction of 4-Chlorochalcone with Ethyl Ace-
toacetate at Different Vibration Frequencies for 40 Minutes
(4) Toda, F.; Takumi, H.; Nagami, M.; Tanaka, K. Hetrocycles
1998, 47, 469.
Entry
Catalyst (equiv)
Vibration
Yieldb (%)
frequency (rpm)a
(5) (a) Bram, G.; Sansoulet, J.; Galons, H.; Miocque, M. Synth.
Commun. 1988, 18, 367. (b) Kim, D. Y.; Huh, S. C.; Kim, S.
M. Tetrahedron Lett. 2001, 42, 6299. (c) Dere, R. T.; Pal, R.
R.; Patil, P. S.; Salunkhe, M. M. Tetrahedron Lett. 2003, 44,
5351.
(6) Loupy, P. Top. Curr. Chem. 2000, 206, 153.
(7) Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
(8) Wang, G.-W.; Murata, Y.; Komatsu, K.; Wan, T. S. M.
Chem. Commun. 1996, 2059.
(9) (a) Wang, G.-W.; Komatsu, K.; Murata, Y.; Shiro, M.
Nature (London) 1997, 387, 583. (b) Komatsu, K.; Wang,
G.-W.; Murata, Y.; Tanaka, T.; Fujiwara, K.; Yamamoto,
K.; Saunders, M. J. Org. Chem. 1998, 63, 9358.
(c) Komatsu, K.; Fujiwara, K.; Murata, Y. Chem. Commun.
2000, 1583. (d) Kunitake, M.; Uemura, S.; Ito, O.; Fujiwara,
K.; Murata, Y.; Komatsu, K. Angew. Chem., Int. Ed. 2002,
41, 969.
1
2
3
4
5
6
None
3500
1800
1200
3500
1800
1200
28
None
Trace
None
No reaction
K2CO3 (0.1)
K2CO3 (0.1)
K2CO3 (0.1)
99
47
19
a The reactions at 1800 rpm and 1200 rpm were run on a Retsch
MM200 mixer mill.
b Isolated yield of 4 by column chromatography.
As shown in Table 3, higher vibration frequency of the vi-
bration mill accelerated the reaction process greatly. It is
easy to understand that the faster the mill vibrates the
higher the mechanical energy, and therefore the local
pressure, applied to the reaction system. Furthermore,
when a mill vibrates at higher speed (or intensity of mill-
ing), the temperature of its capsule should reach a higher
value, which may be advantageous for the diffusion pro-
cess to promote homogenization and alloying in the pow-
ders and thus beneficial for the ongoing reaction.19
(10) Murata, Y.; Kato, K.; Fujiwara, K.; Komatsu, K. J. Org.
Chem. 1999, 64, 3483.
(11) Murata, Y.; Kato, K.; Komatsu, K. J. Org. Chem. 2001, 66,
7235.
(12) Murata, Y.; Suzuki, M.; Komatsu, K. Chem. Commun. 2001,
2338.
(13) Fujiwara, K.; Komatsu, K. Org. Lett. 2002, 4, 1039.
(14) Wang, G.-W.; Zhang, T.-H.; Hao, E.-H.; Jiao, L.-J.; Murata,
Y.; Komatsu, K. Tetrahedron 2003, 59, 55.
(15) Wang, G.-W.; Zhang, T.-H.; Li, Y.-J.; Lu, P.; Zhan, H.; Liu,
Y.-C.; Murata, Y.; Komatsu, K. Tetrahedron Lett. 2003, 44,
4407.
In conclusion, a powerful method is described for Michael
reactions of 1,3-dicarbonyl compounds with chalcones
and azachalcones in quantitative yields in most cases. All
these mechanochemical reactions were conducted under
the solvent-free and the HSVM conditions. The use of the
HSVM technique and catalytic amount of K2CO3 gave
very high product yield and selectivity. The advantages of
mild condition, high yield, short reaction time together
with a straightforward and easy work-up procedure make
the present method convenient, effective and environmen-
tally friendly, which could be a very efficient alternative
to the classic methodology.
(16) General Procedure for the Synthesis of Compounds 3:
A mixture of compound 1 (0.1 mmol), diethyl malonate 2
(15.2 mL, 0.1 mmol) and K2CO3 (1.4 mg, 0.01 mmol) was
vigorously shaken by HSVM for a designated time. The
reaction mixture was collected and washed with water to
remove the small amount of K2CO3, and then dried to give
the crude product 3. The obtained product is essentially pure
and can be further purified by crystallization from petroleum
ether–EtOAc (10:1) at –20 ºC. Products 3c, 3i and 3m were
purified by column chromatography on silica gel with
petroleum ether–EtOAc (5:1) as an eluent.
Selected analytical data:
3f: Mp 93–94 ºC. IR (KBr): 2224, 1752, 1731, 1686 cm–1. 1H
NMR (300 MHz, CDCl3): d = 7.87 (d, J = 7.6 Hz, 2 H), 7.54
(d, J = 8.0 Hz, 2 H), 7.53 (m, 1 H), 7.43 (d, J = 7.6 Hz, 2 H),
7.41 (d, J = 8.0 Hz, 2 H), 4.26–4.14 (m, 3 H), 3.98 (q, J = 7.1
Hz, 2 H), 3.81 (d, J = 9.5 Hz, 1 H), 3.57 (dd, J = 17.3, 4.6 Hz,
1 H), 3.48 (dd, J = 17.3, 9.2 Hz, 1 H), 1.23 (t, J = 7.1 Hz, 3
H), 1.04 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3) d
= 196.90, 167.92, 167.42, 146.41, 136.51, 133.50, 132.26 (2
× C), 129.39 (2 × C), 128.78 (2 × C), 128.10 (2 × C), 118.74,
111.15, 62.02, 61.74, 56.91, 42.08, 40.68, 14.10, 13.90.
HRMS (EI–TOF): m/z [M+] calcd for C23H23NO5: 393.1576;
found: 393.1577.
Acknowledgment
We are grateful to financial support from the National Science Fund
for Distinguished Young Scholars (20125205), Anhui Provincial
Natural Science Foundation (00045306), and Anhui Provincial
Bureau of Personnel Affairs.
Synlett 2004, No. 1, 61–64 © Thieme Stuttgart · New York

64
Z. Zhang et al.
LETTER
3h: Mp 114–115 ºC. IR (KBr): 1743, 1721, 1684 cm–1. 1H
NMR (300 MHz, CDCl3): d = 7.90 (dd, J = 7.8, 1.3 Hz, 2 H),
7.56 (t, J = 7.3 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 2 H), 7.38 (d,
J = 2.0 Hz, 1 H), 7.32 (d, J = 8.3 Hz, 1 H), 7.16 (dd, J = 8.3,
2.0 Hz, 1 H), 4.26–4.11 (m, 3 H), 4.02 (q, J = 7.1 Hz, 2 H),
3.77 (d, J = 9.3 Hz, 1 H), 3.55 (dd, J = 17.2, 4.6 Hz, 1 H),
3.44 (dd, J = 17.2, 9.2 Hz, 1 H),1.25 (t, J = 7.1 Hz, 3 H), 1.09
(t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 197.04,
168.07, 167.55, 141.13, 136.62, 133.48, 132.47, 131.30,
130.45 (2 × C), 128.81 (2 C), 128.18 (2 × C), 128.06, 62.01,
61.79, 57.15, 42.18, 39.87, 14.15, 13.97. HRMS (EI–TOF):
m/z [M+] calcd for C22H22O535Cl2: 436.0844; found:
J = 8.3 Hz, 2 H), 7.47 (d, J = 8.3 Hz, 2 H), 7.46 (m, 1 H),
4.29–4.16 (m, 3 H), 3.96 (q, J = 7.1 Hz, 2 H), 3.96 (dd, J =
18.2, 9.9 Hz, 1 H), 3.82 (d, J = 10.3 Hz, 1 H), 3.62 (dd, J =
18.2, 4.0 Hz, 1 H), 1.25 (t, J = 7.1 Hz, 3 H), 1.03 (t, J = 7.1
Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 198.57, 167.82,
167.47, 153.00, 149.04, 146.84, 137.06, 132.18 (2 × C),
129.59 (2 × C), 127.50, 121.91, 118.81, 111.07, 61.98,
61.64, 57.24, 41.56, 40.53, 14.13, 13.92. HRMS (EI–TOF):
m/z [M+] calcd for C22H22N2O5: 394.1529; found: 394.1528.
3m: Mp 50–52 ºC. IR (KBr): 1750, 1730, 1697 cm–1. 1H
NMR (300 MHz, CDCl3): d = 8.64 (d, J = 4.4 Hz, 1 H), 7.91
(d, J = 7.7 Hz, 1 H), 7.77 (t, J = 7.6 Hz, 1 H), 7.44 (dd, J =
7.0, 5.2 Hz, 1 H), 7.27 (d, J = 8.3 Hz, 2 H), 7.20 (d, J = 8.3
Hz, 2 H), 4.23–4.15 (m, 3 H), 3.95 (q, J = 7.1 Hz, 2 H), 3.90
(dd, J = 17.9, 9.8 Hz, 1 H), 3.78 (d, J = 10.3 Hz, 1 H), 3.57
(dd, J = 17.9, 4.0 Hz, 1 H), 1.25 (t, J = 7.1 Hz, 3 H), 1.03 (t,
J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 198.84,
168.14, 167.73, 153.16, 148.99, 139.59, 137.01, 132.84,
130.02 (2 × C), 128.55 (2 × C), 127.37, 121.93, 61.84, 61.52,
57.73, 41.87, 39.92, 14.16, 13.93. HRMS (EI–TOF): m/z
[M+] calcd for C21H22NO535Cl: 403.1187; found: 403.1184.
HRMS (EI–TOF): m/z [M+] calcd for C21H22NO537Cl:
405.1157; found: 405.1147.
436.0847.
3i: Mp 58–60 ºC. IR (KBr): 1748, 1728, 1682 cm–1. 1H NMR
(300 MHz, CDCl3) d = 7.90 (dd, J = 7.4, 1.2 Hz, 2 H), 7.54
(t, J = 7.3 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 2 H), 6.76 (d, J = 1.1
Hz, 1 H), 6.71 (dd, J = 8.0, 1.1 Hz, 2 H), 6.66 (d, J = 8.0 Hz,
1 H), 5.88 (s, 2 H), 4.20 (qd, J = 7.1, 2.6 Hz, 2 H), 4.10 (td,
J = 9.4, 4.7 Hz, 1 H), 4.01 (q, J = 7.1 Hz, 2 H), 3.75 (d, J =
9.8 Hz, 1 H), 3.50 (dd, J = 16.5, 4.6 Hz, 1 H), 3.39 (dd, J =
16.5, 9.3 Hz, 1 H), 1.25 (t, J = 7.1 Hz, 3 H), 1.08 (t, J = 7.1
Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 197.70, 168.45,
167.83, 147.67, 146.65, 136.95, 134.32, 133.20, 128.71 (2 ×
C), 128.26 (2 × C), 121.65, 108.78, 108.27, 101.06, 61.81,
61.53, 57.90, 42.88, 40.75, 14.18, 14.01. HRMS (EI–TOF):
m/z [M+] calcd for C23H24O7: 412.1522; found: 412.1527.
3j: Mp 66–67 ºC. IR (KBr): 1749, 1730, 1699, 1521, 1348
cm–1. 1H NMR (300 MHz, CDCl3): d = 8.64 (d, J = 4.2 Hz,
1 H), 8.11 (d, J = 8.6 Hz, 2 H), 7.90 (d, J = 7.8 Hz, 1 H), 7.78
(td, J = 7.6, 1.6 Hz, 1 H), 7.53 (d, J = 8.6 Hz, 2 H), 7.45 (dd,
J = 7.0, 4.6 Hz, 1 H), 4.32 (td, J = 10.0, 4.0Hz, 1 H), 4.21
(qd, J = 7.1, 2.5 Hz, 2 H), 3.97 (q, J = 7.1 Hz, 2 H), 3.97 (dd,
J = 18.2, 9.9 Hz, 1 H), 3.85 (d, J = 10.2 Hz, 1 H), 3.64 (dd,
J = 18.2, 4.1 Hz, 1 H), 1.26 (t, J = 7.1 Hz, 3 H), 1.04 (t, J =
7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d = 198.52,
167.80, 167.45, 152.88, 149.08, 148.93, 147.05, 137.13,
129.69 (2 × C), 127.62, 123.64 (2 × C), 121.96, 62.09, 61.76,
57.22, 41.67, 40.24, 14.17, 13.98. HRMS (EI–TOF): m/z
[M+] calcd for C21H22N2O7: 414.1427; found: 414.1424.
3k: Mp 72–74 ºC. IR (KBr): 1748, 1729, 1691, 1531, 1352
cm–1. 1H NMR (300 MHz, CDCl3): d = 8.65 (d, J = 4.3 Hz,
1 H), 8.22 (s, 1 H), 8.03 (dd, J = 7.7, 1.7 Hz, 1 H), 7.90 (d,
J = 7.9 Hz, 1 H), 7.79 (dd, J = 7.4, 1.2 Hz, 1 H), 7.73 (d, J =
8.7 Hz, 1 H), 7.46 (d, J = 5.0 Hz, 1 H), 7.41 (d, J = 8.1 Hz, 1
H), 4.3 2 (td, J = 9.8, 4.1 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H),
3.97 (dd, J = 18.2, 9.9 Hz, 1 H), 3.97 (q, J = 7.1 Hz, 2 H),
3.85 (d, J = 10.1 Hz, 1 H), 3.66 (dd, J = 18.2, 4.0 Hz, 1 H),
1.25 (t, J = 7.1 Hz, 3 H), 1.03 (t, J = 7.1 Hz, 3 H). 13C NMR
(75 MHz, CDCl3): d = 198.61, 167.84, 167.49, 152.92,
149.10, 148.28, 143.36, 137.07, 135.44, 129.29, 127.56,
123.43, 122.29, 121.91, 62.04, 61.71, 57.34, 41.61, 40.11,
14.15, 13.94. HRMS (EI–TOF): m/z [M+] calcd for
3n: Mp 72–73 ºC. IR (KBr): 1755, 1731, 1695 cm–1. 1H
NMR (300 MHz, CDCl3): d = 8.65 (d, J = 4.4 Hz, 1 H), 7.93
(d, J = 7.4 Hz, 1 H), 7.79 (td, J = 7.6, 1.6 Hz, 1 H), 7.45 (m,
1 H), 7.43 (d, J = 2.0 Hz, 1 H), 7.30 (t, J = 8.3 Hz, 1 H), 7.20
(dd, J = 8.3, 2.0 Hz, 1 H), 4.25–4.13 (m, 3 H), 4.00 (q, J =
7.1 Hz, 1 H), 3.90 (dd, J = 18.2, 9.7 Hz, 1 H), 3.77 (d, J =
10.2 Hz, 1 H), 3.58 (dd, J = 18.2, 4.1 Hz, 1 H), 1.25 (t, J =
7.1 Hz, 3 H), 1.06 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz,
CDCl3): d = 198.61, 167.92, 167.54, 152.98, 149.02, 141.43,
137.06, 132.31, 131.09, 130.66, 130.31, 128.19, 127.49,
121.94, 61.94, 61.66, 57.42, 41.62, 39.63, 14.14, 13.94.
HRMS (EI–TOF): m/z [M+] calcd for C21H21NO535Cl2:
437.0797; found: 437.0791. HRMS (EI–TOF): m/z [M+]
calcd C21H21NO535Cl37Cl: 439.0767; found: 439.0744.
3o: Mp 104–105 ºC. IR (KBr): 1743, 1726, 1697 cm–1. 1H
NMR (300 MHz, CDCl3): d = 8.65 (d, J = 4.3 Hz, 1 H), 7.92
(d, J = 7.8 Hz, 1 H), 7.77 (td, J = 7.6, 1.4 Hz, 1 H), 7.42 (m,
1 H), 6.81 (d, J = 1.3 Hz, 1 H), 6.77 (dd, J = 7.9, 1.6 Hz, 1
H), 6.66 (d, J = 7.9 Hz, 1 H), 5.87 (s, 2 H), 4.23–4.10 (m, 3
H), 3.98 (q, J = 7.2 Hz, 2 H), 3.87 (dd, J = 17.7, 9.7 Hz, 1 H),
3.74 (d, J = 10.4 Hz, 1 H), 3.53 (dd, J = 17.7, 4.2 Hz, 1 H),
1.24 (t, J = 7.2 Hz, 1 H), 1.06 (t, J = 7.2 Hz, 1 H). 13C NMR
(75 MHz, CDCl3): d = 199.02, 168.31, 167.87, 153.27,
148.97, 147.53, 146.48, 136.96, 134.75, 127.27, 121.94,
121.82, 108.96, 108.17, 100.98, 61.74, 61.42, 58.16, 42.09,
40.25, 14.17, 14.00. HRMS (EI–TOF): m/z [M+] calcd for
C22H23NO7: 413.1475; found: 413.1477.
(17) Zhang, Z.; Dong, Y.-W.; Wang, G.-W. Chem. Lett. 2003, 32,
966.
C21H22N2O7: 414.1427; found: 414.1428.
(18) Yamawaki, J.; Ando, T.; Hanafusa, T. Chem. Lett. 1981,
1143.
(19) Suryanarayana, C. Prog. Mater. Sci. 2001, 46, 1.
3l: Mp 42–44 ºC. IR (KBr): 2228, 1750, 1732, 1700 cm–1. 1H
NMR (300 MHz, CDCl3): d = 8.64 (d, J = 4.6 Hz, 1 H), 7.91
(d, J = 7.8 Hz, 1 H), 7.78 (td, J = 7.6, 1.6 Hz, 1 H), 7.55 (d,
Synlett 2004, No. 1, 61–64 © Thieme Stuttgart · New York