PEG 400 as a reusable solvent for 1,4-dipolar cycloadditions via a three-component reaction

Article abstract of DOI:10.1055/s-0029-1218762

Isocyanides, dialkyl acetylenedicarboxylates, and ,-unsaturated aldehydes undergo smooth condensation in poly(ethylene glycol) (PEG 400) to afford the corresponding styrylfuran derivatives in good yields. This method provides a convenient route for a wide range of styrylfurans in a one-pot operation via a three-component reaction. The solvent can be recycled and reused for further reactions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218762

PAPER
2069
PEG 400 as a Reusable Solvent for 1,4-Dipolar Cycloadditions via a
Three-Component Reaction
P
E
G
400 as
a
Re.
V
nt
f
or 1,4-Dipolar
.CycloadditioS
ns ubba Reddy,*a D. Somashekar,a A. Mallikarjun Reddy,a J. S. Yadav,a Balasubramanian Sridharb
a
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500607, India
Fax +91(40)27160512; E-mail:
b
Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad 500607, India
Received 4 March 2010; revised 17 March 2010
and isocyanides to produce seven-membered oxepins,
however, instead of the expected annulated product
(Figure 1) a 2-aminofuran was isolated as the sole prod-
uct. Thus treatment of 3-formylchromone 1 (R1 = H) with
Abstract: Isocyanides, dialkyl acetylenedicarboxylates, and a,b-
unsaturated aldehydes undergo smooth condensation in poly(ethyl-
ene glycol) (PEG 400) to afford the corresponding styrylfuran de-
rivatives in good yields. This method provides a convenient route
for a wide range of styrylfurans in a one-pot operation via a three- cyclohexyl isocyanide (2, R2 = cyclohexyl) and dimethyl
component reaction. The solvent can be recycled and reused for fur-
ther reactions.
acetylenedicarboxylate (3a) in PEG 400 gave dimethyl 2-
(cyclohexylamino)-5-(4-oxo-4H-chromen-3-yl)furan-3,4-
Key words: poly(ethylene glycol), three-component reaction,
zwitterions, styrylfurans
dicarboxylate (4a) in 80% yield (Table 1). The structure
of 4a was confirmed by X-ray crystallography (Figure 2).
O
Multicomponent reactions (MCRs) are highly important
because of their wide range of applications in the pharma-
ceutical chemistry for the production of diversified struc-
tural scaffolds and combinatorial libraries for drug
discovery.1 They are extremely convergent, producing a
remarkably high increase of molecular complexity in just
one step.2 The cycloaddition of 1,4-dipoles with various
electrophiles such as aldehydes, imines, quinones, activat-
ed alkenes, and aza-aromatic systems has been reported to
generate a wide range of heterocycles including amino-
furans, pyrroles, and novel spirolactones.3,4 Furthermore,
the cycloaddition of zwitterions derived from isocyanides
and dimethyl acetylenedicarboxylate with phenyl isocy-
anate, diethyl mesoxalate, and dimethyl azodicarboxylate
has also been reported to produce six-membered hetero-
cycles.5,6 Though, the cycloaddition of zwitterions
derived from isocyanides and dimethyl acetylenedicar-
boxylate has been known with simple aldehydes,3 no ex-
amples are reported using 3-formylchromenones to
produce chromenylfurans. Keeping in mind the challeng-
es posed by traditional solvents and also the limitation of
ionic liquids and supercritical fluids, we are particularly
interested in the use of readily available and biologically
compatible poly(ethylene glycol) (PEG) as a recyclable
solvent for cycloaddition reactions.7–9 Although, ionic liq-
uids have been demonstrated to be a recyclable reaction
media, they are relatively expensive and are toxic com-
pared to PEG.10,11 The preparation of ionic liquids re-
quires tedious purification techniques.
O
NH
O
CO2Me
MeO2C
not observed
Figure 1 Expected annulated product
Figure 2 X-ray crystal structure of 4a
Similarly, tert-butyl isocyanide also participated well in
the reaction and the results are presented in Table 1.
Following our interest in zwitterionic chemistry,12 we at-
tempted the annulation of a,b-unsaturated aldehydes with
zwitterions derived from dimethyl acetylenedicarboxylate
Encouraged by the results obtained with 3-formyl-
chromone 1, we turned our attention to other a,b-unsatur-
ated aldehydes 5, isocyanides 2, and dialkyl acetylene-
dicarboxylates 3. Interestingly, the coupling of cinnamal-
dehyde (5, R1 = R2 = H) with zwitterions derived from cy-
SYNTHESIS 2010, No. 12, pp 2069–2074
x
x.
x
x
.
2
0
1
0
Advanced online publication: 29.04.2010
DOI: 10.1055/s-0029-1218762; Art ID: Z05310SS
© Georg Thieme Verlag Stuttgart · New York

2070
B. V. S. Reddy et al.
PAPER
Table 1 Three-Component Reaction for the Synthesis of Chromenylfurans 4 in PEG 400
CO2Me
CO2Me
NHR2
O
O
MeO2C
O
PEG 400
r.t.
R1
CHO
R2 NC
+
+
R1
O
CO2Me
O
4
1
2
3a
Entry
R1
H
R2
Producta
Time (h)
3.0
Yieldb (%)
1
2
3
c-Hex
t-Bu
4a
4b
4c
90
75
82
H
3.0
Me
c-Hex
3.0
a All products were characterized by NMR, IR, and MS.
b Yield refers to pure products after purification.
clohexyl isocyanide (2, R3 = cyclohexyl) and dimethyl cluding tert-butyl isocyanide and 1,1,3,3-tetramethylbutyl
acetylenedicarboxylate (3a) at room temperature in PEG isocyanide, also participated in this reaction (Table 2).
400 afforded dimethyl 2-(cyclohexylamino)-5-styrylfu- However, a,b-unsaturated ketones, such as cyclopenten-
ran-3,4-dicarboxylate (6a) in 90% yield (Table 2, entry one and cyclohexenone, failed to give the 2-aminofuran
1).
derivatives under identical conditions. Similarly, aliphatic
a,b-unsaturated aldehydes, such as acrolein and crotonal-
dehyde, also did not give the desired product. The reaction
was only successful with aryl-substituted a,b-unsaturated
aldehydes. Diethyl acetylenedicarboxylate (3b) was also
Similarly, various conjugated aldehydes such as a-meth-
yl- and 4-(dimethylamino)cinnamaldehydes 5 reacted ef-
fectively with zwitterions to produce styrylfurans 6g–n in
good yields (Table 2, entries 7–14). Other isocyanides, in-
Table 2 Three-Component Reaction for the Synthesis of Styrylfurans Using PEG 400
CO2R4
CO2R4
R4O2C
PEG 400
r.t.
CHO
R3 NC
+
+
NHR3
R2
O
CO2R4
R1
R2
R1
6
5
2
3
Entry
1
R1
R2
R3
R4
Time (h)
3.0
Producta
6a
Yieldb (%)
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
c-Hex
t-Bu
Me
Me
Me
Et
90
90
95
96
94
93
92
89
85
88
87
89
75
76
2
3.0
6b
6c
3
CMe2CH2t-Bu
c-Hex
3.5
4
3.0
6d
6e
5
t-Bu
Et
3.0
6
CMe2CH2t-Bu
c-Hex
Et
3.5
6f
7
Me
Me
Me
Me
Me
Me
H
Me
Me
Me
Et
3.0
6g
8
t-Bu
3.0
6h
6i
9
CMe2CH2t-Bu
c-Hex
3.0
10
11
12
13
14
3.0
6j
t-Bu
Et
3.0
6k
6l
CMe2CH2t-Bu
c-Hex
Et
3.5
NMe2
NMe2
Me
Me
4.0
6m
6n
H
CMe2CH2t-Bu
4.0
a All products were characterized by NMR, IR, and MS.
b Isolated yields after purification.
Synthesis 2010, No. 12, 2069–2074 © Thieme Stuttgart · New York

PAPER
PEG 400 as a Reusable Solvent for 1,4-Dipolar Cycloadditions
2071
MeO2C
N
CO2Me
H
MeO2C
N
CO2Me
CO2Me
CO2Me
+
NC
R
O
R
O
CO2Me
MeO2C
R
N
H
O
Scheme 1 A plausible reaction mechanism
Dimethyl (E)-2-(Cyclohexylamino)-5-styrylfuran-3,4-dicarbox-
ylate (6a); Typical Procedure
equally effective for this conversion (Table 2, entries 4–6
and 10–12). The structure of 6a was characterized by 1H
and 13C NMR, IR, and HRMS. Mechanistically, the isocy-
anide may initially react with dimethyl acetylenedicar-
boxylate to generate a 1,4-dipole. This highly reactive
zwitterion undergoes subsequent cyclization with the a,b-
unsaturated aldehyde to give the desired styrylfuran
(Scheme 1).
A mixture of cyclohexyl isocyanide (197 mg, 1.8 mmol) and
DMAD (257 mg, 1.8 mmol) in PEG-400 (5 mL) was purged with
N2 at r.t. After 15 min, cinnamaldehyde (200 mg, 1.51 mmol) was
added and then the resulting mixture was allowed to stir at r.t. for 3–
4 h. After completion of the reaction (TLC monitoring), the mixture
was extracted with Et2O (2 ×). The combined ether layers were con-
centrated in vacuo. The resulting crude product was purified by col-
umn chromatography (silica gel, EtOAc–hexanes) to give the pure
styrylfuran derivative as a yellow liquid.
The effects of various solvents, such as water, tetrahydro-
furan, and benzene, were studied for this conversion to 6a:
PEG 400 appeared to give the best results. None of the de-
sired product was formed in water at room temperature.
The reaction proceeded well at room temperature in PEG
400, whereas the same reaction was successful in benzene
under reflux conditions. After completion of the reaction,
the mixture was diluted with anhydrous diethyl ether and
stirred for 10 minutes and then allowed the layers were al-
lowed to separate out and the ether layer was decanted.
This process was repeated twice to obtain the product in
diethyl ether whereas the mother liquor (PEG) was kept
aside for further runs. A second run was performed with-
out any modification using recovered PEG 400. Thus
treatment of cinnamaldehyde (1 mmol) with cyclohexyl
isocyanide (1 mmol) and dimethyl acetylenedicarboxylate
(1 mmol) in recovered PEG 400 gave the product 6a in
89% yield with the same purity as in first run. The effi-
cient recycling of the reaction medium was then proved
by additional experiments until a fifth run. Similar yields
and reaction rates were achieved in all the runs.
IR (KBr): 3351, 2934, 2855, 1722, 1670, 1612, 1473, 1225, 1149,
1083 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.43 (d, J = 7.3 Hz, 2 H), 7.28 (t,
J = 7.7 Hz, 2 H), 7.16 (m, 1 H), 7.05 (d, J = 16.0 Hz, 1 H), 6.92 (d,
J = 8.1 Hz, 1 H), 6.84 (d, J = 16.2 Hz, 1 H), 3.80 (s, 3 H), 3.75 (s, 3
H), 3.70 (m, 1 H), 2.11–1.21 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 165.0, 163.8, 161.7, 145.0, 136.4,
128.8, 128.4, 127.6, 127.6, 126.2, 113.9, 86.5, 51.7, 51.1, 50.8,
33.1, 25.2, 24.2.
MS (ESI): m/z = 384 [M + H]+, 406 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C22H25NO5Na: 406.1630;
found: 406.1641.
Dimethyl 2-(Cyclohexylamino)-5-(4-oxo-4H-chromen-3-yl)fu-
ran-3,4-dicarboxylate (4a)
Yellow solid; mp 138–139 °C.
IR (KBr): 3355, 2930, 1736, 1667, 1613, 1464, 1226, 1097 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.27–8.21 (m, 2 H), 7.68–7.62 (m,
1 H), 7.41–7.32 (m, 2 H), 6.72 (d, J = 7.7 Hz, 1 H), 3.82 (s, 3 H),
3.72 (s, 3 H), 3.69 (m, 1 H), 2.11–1.20 (m, 10 H).
In summary, we have demonstrated the use of PEG 400 as 13C NMR (75 MHz, CDCl3): d = 173.7, 164.9, 161.2, 155.6, 152.9,
133.7, 133.1, 126.4, 125.4, 123.7, 117.9, 117.8, 115.6, 105.3, 87.2,
52.3, 51.3, 51.1, 33.3, 29.6, 24.4.
MS (ESI): m/z = 426 [M + H]+, 448 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H23NO7Na: 448.1372;
an efficient reaction medium for the 1,4-dipolar cycload-
dition of a,b-unsaturated aldehydes with zwitterions
derived from isocyanides and dialkyl acetylenedicarboxy-
lates. The cycloaddition is more rapid and high-yielding
in PEG 400 at room temperature over conventional sol-
vents.
found: 448.1361.
Dimethyl 2-(tert-Butylamino)-5-(4-oxo-4H-chromen-3-yl)fu-
ran-3,4-dicarboxylate (4b)
IR spectra were recorded on Perkin-Elmer FT-IR 240-c spectropho-
tometer. 1H and 13C NMR spectra were recorded in CDCl3 solvent
on a Bruker AV-300 NMR spectrometer with respect to internal
TMS. MS were obtained on Finnigan MAT1020B and Agilent tech-
nologies LC/MSD trapSL spectrometer operating at 70 eV using a
direct inlet system.
Yellow solid; mp 144–145 °C.
IR (KBr): 3448, 2924, 2854, 1737, 1664, 1609, 1558, 1464, 1404,
1350, 1311, 1215, 1093 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.27–8.24 (m, 2 H), 7.68–7.63 (m,
1 H), 7.46–7.38 (m, 2 H), 6.94 (s, 1 H), 3.87 (s, 3 H), 3.76 (s, 3 H),
1.48 (s, 9 H).
Synthesis 2010, No. 12, 2069–2074 © Thieme Stuttgart · New York

2072
B. V. S. Reddy et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 173.7, 164.9, 161.2, 155.6, 152.9,
133.7, 133.1, 126.4, 125.4, 123.7, 117.9, 117.8, 115.6, 105.3, 87.2,
52.3, 51.3, 51.1, 33.3.
13C NMR (75 MHz, CDCl3): d = 164.89, 163.8, 161.8, 144.7, 136.7,
128.9, 128.6, 127.6, 127.3, 126.3, 114.1, 86.8, 60.8, 59.5, 51.3,
33.3, 29.6, 24.4, 14.3, 14.2.
MS (ESI): m/z = 400 [M + H]+, 422 [M + Na]+.
MS (ESI): m/z = 434 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C21H22NO7: 400.1396; found:
HRMS (ESI): m/z [M + Na]+ calcd for C24H29NO5Na: 434.1943;
400.1388.
found: 434.1957.
Dimethyl 2-(Cyclohexylamino)-5-(6-methyl-4-oxo-4H-
chromen-3-yl)furan-3,4-dicarboxylate (4c)
Yellow solid; mp 154–155 °C.
Diethyl (E)-2-(tert-Butylamino)-5-styrylfuran-3,4-dicarboxy-
late (6e)
Yellow liquid.
IR (KBr): 3363, 2928, 1742, 1668, 1476, 1228, 1100 cm–1.
IR (KBr): 3327, 2978, 1728, 1666, 1604, 1466, 1210, 1086 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.22 (s, 1 H), 8.05 (s, 1 H), 7.52–
7.34 (m, 2 H), 6.65 (d, J = 8.1 Hz, 1 H), 3.91 (s, 3 H), 3.72 (s, 3 H),
3.68 (m, 1 H), 2.42 (s, 3 H), 2.02–1.33 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 173.7, 164.9, 161.2, 153.9, 152.9,
135.4, 134.9, 133.4, 126.5, 125.6, 124.2, 123.3, 117.7, 115.3, 87.25,
52.7, 51.3, 51.08, 33.3, 25.3, 24.4, 20.8.
MS (ESI): m/z = 440 [M + H]+, 462 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H25NO7Na: 462.1528;
1H NMR (300 MHz, CDCl3): d = 7.42 (d, J = 7.8 Hz, 2 H), 7.25–7.3
(m, 2 H), 7.18 (t, J = 7.8 Hz, J = 6.8 Hz, 1 H), 7.12 (s, 1 H), 7.07 (d,
J = 15.6 Hz, 1 H), 6.82 (d, J = 15.6 Hz, 1 H), 4.32 (q, J = 7.8 Hz, 2
H), 4.21 (q, J = 6.8 Hz, 2 H), 1.50 (s, 9 H), 1.38 (t, J = 7.8 Hz, 3 H),
1.31 (t, J = 6.8 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 164.9, 163.8, 162.1, 145.0, 136.6,
128.5, 127.7, 127.4, 126.3, 114.56, 114.08, 87.75, 60.9, 59.5, 52.6,
29.6, 14.3, 14.2.
MS (ESI): m/z = 386 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C22H27NO5Na: 408.1793;
found: 462.1518.
Dimethyl (E)-2-(tert-Butylamino)-5-styrylfuran-3,4-dicarboxy-
found: 408.1786.
late (6b)
Pale yellow liquid.
Diethyl (E)-2-Styryl-5-(2,4,4-trimethylpentan-2-ylamino)fu-
ran-3,4-dicarboxylate (6f)
Brown liquid.
IR (KBr): 3421, 2923, 1728, 1664, 1604, 1467, 1216, 1085 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42 (d, J = 7.3 Hz, 2 H), 7.24–
7.31 (m, 3 H), 7.16–7.21 (m, 1 H), 7.05 (d, J = 16.2 Hz, 1 H), 6.81
(d, J = 16.2 Hz, 1 H), 4.32 (q, J = 7.1 Hz, 2 H), 4.22 (q, J = 7.1 Hz,
2 H), 1.81 (s, 2 H), 1.55 (s, 6 H), 1.40 (t, J = 7.1 Hz, 3 H), 1.31 (t,
J = 7.1 Hz, 3 H), 1.0 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.9, 163.8, 161.9, 144.9, 136.5,
128.5, 127.6, 127.3, 126.3, 114.6, 114.0, 87.5, 60.8, 59.4, 56.3,
52.9, 31.5, 31.3, 30.1, 14.3, 14.2.
IR (KBr): 3332, 2924, 2854, 1726, 1669, 1606, 1470, 1212, 1086
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.43 (d, J = 7.3 Hz, 2 H), 7.28 (t,
J = 7.7 Hz, 2 H), 7.25 (d, J = 7.1 Hz, 1 H), 7.13 (s, 1 H), 7.05 (d,
J = 16.2 Hz, 1 H), 6.84 (d, J = 16.2 Hz, 1 H), 3.81 (s, 3 H), 3.70 (s,
3 H), 1.50 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.2, 164.0, 162.1, 145.4, 136.5,
128.9, 128.5, 127.8, 127.7, 126.4, 114.0, 87.5, 52.7, 51.8, 50.9,
29.6.
MS (ESI): m/z = 358 [M + H]+, 380 [M + Na]+.
HRMS (ESI) m/z [M + Na]+ calcd for C20H23NO5Na: 380.1473;
MS (ESI): m/z = 442 [M + H]+, 464 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C26H35NO5Na: 464.2419;
found: 380.1466.
Dimethyl (E)-2-Styryl-5-(2,4,4-trimethylpentan-2-ylamino)fu-
ran-3,4-dicarboxylate (6c)
Pale yellow liquid.
IR (KBr): 3333, 2947, 1726, 1669, 1607, 1472, 1217, 1085 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42 (d, J = 7.5 Hz, 2 H), 7.30–
7.23 (m, 4 H), 7.05 (d, J = 16.6 Hz, 1 H), 6.85 (d, J = 15.8 Hz, 1 H),
3.87 (s, 3 H), 3.75 (s, 3 H), 1.81 (s, 2 H), 1.56 (s, 6 H), 1.04 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.9, 163.8, 161.9, 144.9, 136.5,
128.5, 127.6, 127.3, 126.3, 114.6, 114.0, 87.5, 60.8, 59.4, 56.3,
52.9, 31.5, 31.3, 30.1.
MS (ESI): m/z = 436 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C24H31NO5Na: 436.2099;
found: 464.2412.
Dimethyl (E)-2-(Cyclohexylamino)-5-(1-phenylprop-1-en-2-
yl)furan-3,4-dicarboxylate (6g)
Brown liquid.
IR (KBr): 3356, 2932, 2855, 1737, 1679, 1614, 1475, 1223, 1148,
1103 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–7.24 (m, 4 H), 7.20–7.11 (m,
1 H), 6.80 (s, 1 H), 6.60 (d, J = 8.3 Hz, 1 H), 3.83 (s, 3 H), 3.74 (s,
3 H), 3.70 (m, 1 H,), 2.03 (s, 3 H), 1.81–1.22 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 166.2, 164.5, 160.6, 142.0, 136.9,
129.1, 128.0, 126.5, 125.2, 125.0, 114.0, 87.3, 52.4, 51.3, 50.9,
33.2, 29.5, 25.3, 14.1.
found: 436.2107.
MS (ESI): m/z = 398 [M + H]+, 420 [M + Na]+.
Diethyl (E)-2-(Cyclohexylamino)-5-styrylfuran-3,4-dicarboxy-
late (6d)
HRMS (ESI): m/z [M + Na]+ calcd for C23H27NO5Na: 420.1786;
found: 420.1779.
Dark brown liquid.
Dimethyl (E)-2-(tert-Butylamino)-5-(1-phenylprop-1-en-2-
yl)furan-3,4-dicarboxylate (6h)
Brown liquid.
IR (KBr): 3341, 2961, 1737, 1677, 1609, 1461, 1212, 1092 cm–1.
IR (KBr): 3342, 2930, 1726, 1668, 1610, 1472, 1222, 1074 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42 (d, J = 7.5 Hz, 2 H), 7.25 (t,
J = 7.5 Hz, 2 H), 7.15 (d, J = 6.7 Hz, 1 H), 7.08 (d, J = 15.8 Hz, 1
H), 6.93 (d, J = 8.3 Hz, 1 H), 6.84 (d, J = 15.8 Hz, 1 H), 4.25 (q,
J = 7.5 Hz, 2 H), 4.22 (q, J = 6.7 Hz, 2 H), 3.71 (s, 1 H), 2.06–1.42
(m, 10 H), 1.37 (t, J = 7.5 Hz, 3 H), 1.25 (t, J = 6.7 Hz, 3 H).
Synthesis 2010, No. 12, 2069–2074 © Thieme Stuttgart · New York

PAPER
PEG 400 as a Reusable Solvent for 1,4-Dipolar Cycloadditions
2073
1H NMR (300 MHz, CDCl3): d = 7.31–7.25 (m, 4 H), 7.22–7.17 (m,
1 H), 6.84 (d, J = 10 Hz, 2 H), 3.83 (s, 3 H), 3.73 (s, 3 H), 2.04 (s, 3
H), 1.49 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 166.2, 164.6, 160.9, 142.5, 136.9,
129.1, 128.0, 126.6, 125.3, 125.0, 113.7, 88.2, 52.5, 52.4, 50.9,
29.5, 14.1.
MS (ESI): m/z = 372 [M + H]+, 394 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C21H25NO5Na: 394.163;
J = 7.1 Hz, 2 H), 2.07 (s, 3 H), 1.70 (s, 2 H), 1.50 (s, 6 H), 1.35 (t,
J = 7.1 Hz, 3 H), 1.25 (t, J = 7.1 Hz, 3 H), 1.04 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.8, 164.3, 160.9, 142.1, 136.9,
129.0, 128.0, 126.5, 125.1, 125.0, 114.1, 88.3, 61.4, 59.4, 52.4,
33.6, 31.7, 29.7, 22.5, 14.2, 14.1, 13.9.
MS (ESI): m/z = 456 [M + H]+, 478 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C27H38NO5: 456.2749; found:
456.2736.
found: 394.1620.
Dimethyl (E)-2-(Cyclohexylamino)-5-[4-(dimethylamino)styr-
yl]furan-3,4-dicarboxylate (6m)
Dark brown liquid.
Dimethyl (E)-2-(1-Phenylprop-1-en-2-yl)-5-(2,4,4-trimethyl-
pentan-2-ylamino)furan-3,4-dicarboxylate (6i)
Yellow liquid.
IR (KBr): 3342, 2952, 1737, 1676, 1609, 1472, 1214, 1091 cm–1.
IR (KBr): 3423, 2923, 2853, 1731, 1672, 1611, 1466, 1228, 1083
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–7.18 (m, 5 H), 6.91 (s, 1 H),
6.81 (s, 1 H), 3.82 (s, 3 H), 3.71 (s, 3 H), 2.05 (s, 3 H), 1.70 (s, 2 H),
1.50 (s, 6 H), 1.04 (s, 9 H).
1H NMR (300 MHz, CDCl3): d = 7.35 (d, J = 8.7 Hz, 2 H), 6.91–
6.86 (m, 2 H), 6.81–6.75 (m, 3 H), 3.82 (s, 3 H), 3.76 (s, 3 H), 3.70
(m, 1 H), 3.01 (s, 6 H), 2.01–1.27 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 166.5, 164.9, 161.0, 142.5, 137.2,
129.3, 128.3, 126.8, 125.4, 125.2, 114.0, 88.3, 56.4, 53.3, 52.6,
51.1, 31.5, 30.2, 29.8, 14.3.
13C NMR (75 MHz, CDCl3): d = 168.9, 165.4, 161.8, 150.1, 146.7,
136.2, 128.7, 127.7, 127.7, 112.2, 110, 82.9, 51.7, 51.3, 50.9, 40.3,
33.4, 29.6, 24.5.
MS (ESI): m/z = 428 [M + H]+, 450 [M + Na]+.
MS (ESI): m/z = 427 [M + H]+, 449 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C25H33NO5Na: 450.2256;
HRMS (ESI): m/z [M + Na]+ calcd for C24H30NO5Na: 449.2052;
found: 450.2258.
found: 449.2057.
Diethyl (E)-2-(Cyclohexylamino)-5-(1-phenylprop-1-en-2-yl)fu-
ran-3,4-dicarboxylate (6j)
Yellow liquid.
Dimethyl (E)-2-[4-(Dimethylamino)styryl]-5-(2,4,4-trimethyl-
pentan-2-ylamino)furan-3,4-dicarboxylate (6n)
Dark brown liquid.
IR (KBr): 3354, 2930, 1743, 1675, 1466, 1219, 1073 cm–1.
IR (KBr): 3447, 2995, 1729, 1664, 1604, 1464, 1217, 1084 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–7.20 (m, 4 H), 7.21–7.12 (m,
1 H), 6.81 (s, 1 H), 6.63 (d, J = 7.9 Hz, 1 H), 4.25 (q, J = 7.1 Hz, 2
H), 4.15 (q, J = 7.1 Hz, 2 H), 3.69 (s, 1 H), 2.01 (s, 3 H), 1.82–1.21
(m, 10 H), 1.35 (t, J = 7.1 Hz, 3 H), 1.28 (t, J = 7.1 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.25 (d, J = 8.3 Hz, 2 H), 6.95 (d,
J = 16.2 Hz, 2 H), 6.68 (d, J = 16 Hz, 2 H), 3.82 (s, 3 H), 3.71 (s, 3
H), 3.68 (m, 1 H), 3.02 (s, 6 H), 1.81 (s, 2 H), 1.48 (s, 6 H), 1.01 (s,
9 H).
13C NMR (75 MHz, CDCl3): d = 165.5, 164.1, 160.5, 141.6, 136.9,
128.9, 127.9, 126.4, 125.0, 124.9, 114.4, 87.5, 61.2, 59.3, 51.1,
33.1, 29.4, 25.2, 24.2, 14.1, 13.8.
13C NMR (75 MHz, CDCl3): d = 166.6, 164.5, 162.0, 150.2, 146.9,
135.6, 129.7, 128.7, 127.8, 112.3, 110.1, 86.7, 56.3, 53.1, 51.8,
50.9, 40.4, 31.4, 30.2, 29.6.
MS (ESI): m/z = 426 [M + H]+, 448 [M + Na]+.
MS (ESI): m/z = 457 [M + H]+, 479 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C25H32NO5: 426.228; found:
HRMS (ESI): m/z [M + Na]+ calcd for C26H36NO5Na: 479.2521;
426.2287.
found: 479.2510.
Diethyl (E)-2-(tert-Butylamino)-5-(1-phenylprop-1-en-2-yl)fu-
ran-3,4-dicarboxylate (6k)
Acknowledgment
Yellow liquid.
D.S.S. and A.M.R. thanks CSIR, New Delhi for the award of fel-
lowships.
IR (KBr): 3339, 2978, 1734, 1673, 1465, 1208, 1094, 1047 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–7.23 (m, 5 H), 6.82 (s, 2 H),
4.25 (q, J = 7.5 Hz, 2 H), 4.15 (q, J = 7.5 Hz, 2 H), 2.06 (s, 3 H),
1.40 (s, 9 H), 1.35 (t, J = 7.5 Hz, 3 H), 1.28 (t, J = 7.5 Hz, 3 H).
References
13C NMR (75 MHz, CDCl3): d = 165.8, 164.3, 160.9, 142.1, 136.9,
129.0, 128.0, 126.5, 125.1, 125.0, 114.1, 88.3, 61.4, 59.4, 52.4,
29.5, 14.2, 14.1, 13.9.
MS (ESI): m/z = 400 [M + H]+, 422 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C23H29NO5Na: 422.1943;
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S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123.
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Diethyl (E)-2-(1-Phenylprop-1-en-2-yl)-5-(2,4,4-trimethylpen-
tan-2-ylamino)furan-3,4-dicarboxylate (6l)
Pale yellow liquid.
IR (KBr): 3339, 2978, 1735, 1672, 1609, 1472, 1249, 1084 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–7.22 (m, 4 H), 7.20–7.12 (m,
1 H), 6.91 (s, 1 H), 6.80 (s, 1 H), 4.25 (q, J = 7.1 Hz, 2 H), 4.15 (q,
Synthesis 2010, No. 12, 2069–2074 © Thieme Stuttgart · New York

2074
B. V. S. Reddy et al.
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