One-pot, three-component route to spiropyrrolidine derivatives via a 1,3-dipolar cycloaddition reaction

Article abstract of DOI:10.3184/174751911X556846

A series of novel spiropyrrolidine derivatives were synthesised via three-component 1,3-dipolar cycloaddition reactions of 1-(1-methylpyrrole-2-yl)- 3-aryl-2-cyano-1-propenones, isatin and sarcosine in refluxing methanol. The method affords a fast one-pot

Full text of DOI:10.3184/174751911X556846

JOURNAL OF CHEMICAL RESEARCH 2011
RESEARCH PAPER 121
FEBRUARY, 121–123
One-pot, three-component route to spiropyrrolidine derivatives via a
1,3-dipolar cycloaddition reaction
Guo-Liang Fenga*, Hong-Li Zhanga and Li-Jun Genga,b
aSchool of Science, Hebei University of Science andTechnology, Yuhua East Road, Shijiazhuang 050018, P. R. China
bDepartment of Chemistry, School of Science, Tianjin University, Weijin Road, Tianjin 300072, P. R. China
A series of novel spiropyrrolidine derivatives were synthesised via three-component 1,3-dipolar cycloaddition
reactions of 1-(1-methylpyrrole-2-yl)-3-aryl-2-cyano-1-propenones, isatin and sarcosine in refluxing methanol.
The method affords a fast one-pot synthesis of spiroheterocycles in high yields. Their structures were established by
1H NMR, IR and elementary analysis.
Keywords: spiropyrrolidine derivatives, 1-(1-methylpyrrole-2-yl)-3-aryl-2-cyano-1-propenones, isatin, sarcosine, 1,3-dipolar
cycloaddition reaction
Multicomponent 1,3-dipolar cycloaddition are considered to
be one of the most useful processes for the construction of a
variety of five-membered heterocyclic compounds, such as
pyrrolidines, pyrrolines and pyrroles.1,2 These strategies offer
significant advantages over more traditional approaches,
allowing the construction of complex structures from easily
available starting materials in a single operation without the
need for the isolation of intermediates. Azomethine ylides,
which are zwitterionic and are composed of one positively
charged nitrogen atom and two terminal sp2-hybridised carbon
atoms, have gained significance in recent years for the
construction of nitrogen containing five-membered heterocy-
cles.3–6 Spiroheterocycles including spiropyrrolidines represent
an important class of substances characterised by their high
biological activities.7–10 Oxindole derivatives at C3 as spiro-
carbo- have served as potential synthetic intermediates for the
total synthesis of alkaloids, drug intermediates and clinical
pharmaceuticals.11,12
In our initial study, the different refluxing solvents were
tested in the synthesis of 4a. The results were summarised in
Table 1. The reactions in 1,4-dioxane and glycol monomethyl
ether provided none of the desired product. When the reactions
were carried out in ethanol, ethanol/water or methanol/water,
compound 4a was obtained in moderate yields (Table 1, entries
1–5). However, the reaction proceeded well in methanol to
give a good yield of 83% in a short time (Table 1, entry 6).
To extend the scope of this new procedure for the synthesis
of spiropyrrolidines, a series of reactions were carried out with
substituted derivatives 1 under these optimised conditions. We
found that the reaction proceeded smoothly and the desired
products were obtained in excellent yields. Interestingly, the
electronic effect of the substituent on the aromatic ring had no
significant influence on the reaction yields (Table 2).
The structures of the compounds 4a–k were fully supported
1
by IR, H NMR and elementary analysis as demonstrated
Recently, we described a new and efficient synthesis of pyr-
idine derivatives by multicomponent reactions.13,14 In the light
of our interest in multicomponent syntheses, we now describe
an efficient method for the preparation of spiropyrrolidine
derivatives by the 1,3-dipolar cycloaddition of azomethine
ylides from isatin and sarcosine with 1-(1-methylpyrrole-
2-yl)-3-aryl-2-cyano-1-propenones in methanol (Scheme 1).
Table 1 Optimisation of reaction conditions for the three-
component reactions
Entry Solvent
Time/h
Yield/%a
1
2
3
4
5
6
1,4-dioxane
glycol monomethyl ether
ethanol
Ethanol : water(1:1)
Methanol : water(1:1)
methanol
8
0
0
63
32
44
83
8
5
5.5
4
1-(1-Methylpyrrole-2-yl)-3-aryl-2-cyano-1-propenones
1
were prepared through a reaction of 3-(1-methylpyrrole-2-yl)-
3-oxopropanenitrile 5 and aromatic aldehydes 6 in refluxing
glycol monomethyl ether (Scheme 2).
2
a Isolated yield.
Scheme 1
Scheme 2
* Correspondent. E-mail: fgl197012@163.com

122 JOURNAL OF CHEMICAL RESEARCH 2011
Table 2 Three-component synthesis of spiropyrrolidines in
methanol
Elementary analyses were performed by a Carlo-Erba EA1110
CNNO-S analyser.
Synthesis of 4a–k: A mixture of 1-(1-methylpyrrole-2-yl)-3-aryl-2-
cyano-1-propenone 1 (1mmol), isatin 2 (1mmol), sarcosine 3 (1mmol)
and methanol (20 mL) was refluxed for the specified period of time.
After complete conversion as indicated by TLC, the mixture was
allowed to cool to room temperature and the solvent was removed in
vacuo. The crude product was extracted with dichloromethane and
washed with H2O (3×15 mL) and the organic layer dried over MgSO4.
The solvent was removed in vacuo and the crude product was
subjected to flash chromatography to afford the pure product (4a–k).
Entry
R
Producta Time/h Yield/%b M. p. (°C)
1
2
H
4-CH3
4a
4b
4c
4d
4e
4f
4g
4h
4i
2
83
84
76
88
86
89
88
82
83
85
87
208–209 °C
233–234 °C
209 °C
193–195 °C
217–218 °C
231 °C
229–230 °C
202–203 °C
217–218 °C
205–206 °C
222–223 °C
2
3
4-N(CH3)2
2-OCH3
4-CH(CH3)2
3,4-(CH3)2
2,4-(CH3)2
3-NO2
4-NO2
2,4-Cl2
3,4-(CH=
CH-CH=CH)
1.5
1.5
1.5
1.5
1.5
2
4
5
6
7
1
8
4a: H NMR (500 MHz, CDCl3): δ 8.01 (s, 1H), 7.60 (s, 2H),
9
2
7.36−7.26 (m, 4H), 7.20−7.17 (m, 2H), 6.67 (t, 2H, J = 8.5 Hz), 6.13
(dd, 1H, J = 4.5 Hz and J = 2.0 Hz), 5.64 (dd, 1H, J = 4.5 Hz and J =
2.0 Hz), 5.38 (dd, 1H, J = 10.0 Hz and J = 7.0 Hz), 3.80−3.70 (m, 5H),
2.23 (s, 3H). IR(KBr): 3339, 3064, 3031, 2943, 2864, 2236, 1724,
1618, 1522, 1467 cm−1. Anal. Calcd for C25H22N4O2: C, 73.15; H, 5.40;
N, 13.65; Found: C, 73.04; H, 5.43; N, 13.53%.
10
11
4j
4k
2
2
a The products were characterised by 1H NMR, IR and
elementary analysis.
b Isolated yield.
4b: 1H NMR (500 MHz, CDCl3): δ 8.00 (s, 1H), 7.50 (d, 2H, J = 8.5
Hz), 7.37 (s, 1H), 7.32−7.28 (m, 1H), 7.20−7.16 (m, 3H), 6.71−6.67
(m, 2H), 6.16 (dd, 1H, J = 4.5 Hz and J = 2.0 Hz), 5.65 (dd, 1H, J =
4.5 Hz and J = 2.0 Hz), 5.36 (dd, 1H, J = 10.0 Hz and J = 7.0 Hz),
3.78−3.71 (m, 5H), 2.35 (s, 3H), 2.23 (s, 3H). IR(KBr): 3318, 3107,
2960, 2865, 2238, 1726, 1615, 1517, 1471 cm−1. Anal. Calcd for
C26H24N4O2: C, 73.56; H, 5.70; N, 13.20; Found: C, 73.62; H, 5.83;
N, 13.31%.
for compound 4a. The IR spectrum of 4a showed two peaks
at 1724 cm−1 and 1618 cm−1 which correspond to the isatin and
1-(1-methylpyrrole-2-yl)-3-aryl-2-cyano-1-propenones ring
carbonyls, respectively. The peak at 2236 cm−1 correspond to
the CN. In the 1H NMR spectrum of 4a, the –NH proton exhib-
ited a singlet at δ 8.01. The –NCH3 protons of the pyrrolidine
exhibited a singlet at δ 2.23. The stereochemistry of the
products has not been established.
Based on the above results, a possible mechanism for the
reaction was proposed (Scheme 3). The isatin 2 reacts with
sarcosine 3 to give intermediate 7 which underwent thermal
decarboxylation leading to the azomethine ylides 8. 1,3-
Dipolar cycloaddition of 1-(1-methylpyrrole-2-yl)-3-aryl-
2-cyano-1-propenones 1 with azomethine ylides 8 produced
spiropyrrolidines 4.
In summary, we have synthesised a number of interesting
novel spiro compounds starting from 1-(1-methylpyrrole-2-
yl)-3-aryl-2-cyano-1-propenones by 1,3-dipolar cycloaddition
reaction. The experimental simplicity, compatibility with vari-
ous functional groups, short reaction times and efficient yields
made this procedure attractive to synthesise a variety of these
derivatives.
4c: 1H NMR (500 MHz, CDCl3): δ 8.01 (s, 1H), 7.44 (d, 2H, J = 7.0
Hz), 7.28 (s, 1H), 7.18−7.15 (m, 2H), 6.70−6.65 (m, 4H), 6.15 (dd,
1H, J = 4.5 Hz and J = 2.0 Hz), 5.66 (dd, 1H, J = 4.5 Hz and J = 2.0
Hz), 5.26 (dd, 1H, J = 10.0 Hz and J = 7.0 Hz), 3.75 (s, 3H), 3.72−3.69
(m, 2H), 2.93 (s, 6H), 2.23 (s, 3H). IR(KBr): 3314, 3103, 2961, 2856,
2790, 2239, 1724, 1715, 1618, 1512, 1470 cm−1. Anal. Calcd for
C27H27N5O2: C, 71.50; H, 6.00; N, 15.44; Found: C, 71.60; H, 6.11;
N, 15.35%.
1
4d: H NMR (500 MHz, CDCl3): δ 7.95 (s, 1H), 7.88 (s, 1H),
7.29−7.26 (m, 3H), 7.12 (t, 1H, J = 7.5 Hz), 7.06 (t, 1H, J = 7.5 Hz),
6.79 (d, 1H, J = 8.0 Hz), 6.66−6.63 (m, 2H), 6.11 (dd, 1H, J = 4.5 Hz
and J = 2.0 Hz), 5.67 (dd, 1H, J = 4.5 Hz and J = 2.0 Hz), 5.63 (dd,
1H, J = 9.5 Hz and J = 7.0 Hz), 3.78 (s, 3H), 3.71−3.68 (m, 2H), 3.34
(s, 3H), 2.18 (s, 3H). IR(KBr):3450, 3301, 2980, 2858, 2236, 1736,
1617, 1470 cm−1. Anal. Calcd for C26H24N4O3: C, 70.89; H, 5.49;
N, 12.72; Found: C, 70.78; H, 5.42; N, 12.84%.
4e: 1H NMR (500 MHz, CDCl3): δ 8.00 (s, 1H), 7.51 (d, 2H, J = 8.0
Hz), 7.42−7.25 (m, 2H), 7.20−7.15 (m, 3H), 6.68 (d, 1H, J = 7.5 Hz),
6.65 (t, 1H, J = 2.0 Hz), 6.10 (dd, 1H, J = 4.5 Hz and J = 2.5 Hz), 5.63
(dd, 1H, J = 4.5 Hz and J = 2.5 Hz), 5.34 (d, 1H, J = 8.5 Hz ), 3.75−3.71
(m, 5H), 2.92−2.86 (m, 1H), 2.23 (s, 3H), 1.24 (d, 6H, J = 7.0 Hz).
IR(KBr): 3310, 3104, 2961, 2859, 2793, 2362, 1726, 1713, 1616,
1521, 1472 cm−1. Anal. Calcd for C28H28N4O2: C, 74.31; H, 6.24;
N, 12.38; Found: C, 74.36; H, 6.23; N, 12.31%.
Experimental
Melting points were recorded on an electrothermal digital melting
point apparatus and are uncorrected. H NMR spectra were deter-
mined on a Varian VXP-500 spectrometer using CDCl3 as solvent and
tetramethylsilane (TMS) as internal reference. IR spectra was obtained
on a Nicolet FT-IR 6700 spectrophotometer using KBr pellets.
1
4f: 1H NMR (500 MHz, CDCl3): δ 8.01 (s, 1H), 7.34−7.27 (m, 4H),
7.17 (t, 1H, J = 7.5 Hz), 7.10 (d, 1H, J = 7.5 Hz), 6.68−6.64 (m, 2H),
6.13 (dd, 1H, J = 4.0 Hz and J = 2.5 Hz), 5.64 (dd, 1H, J = 4.5 Hz and
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2011 123
J = 2.5 Hz), 5.26 (dd, 1H, J = 10.0 Hz and J = 7.0 Hz), 3.76 (s, 3H),
3.74−3.70 (m, 2H), 2.25 (s, 3H), 2.24 (s, 3H) 2.22 (s, 3H). IR(KBr):
3314, 3106, 2862, 2380, 1742, 1612, 1470 cm−1. Anal. Calcd for
C27H26N4O2: C, 73.95; H, 5.98; N, 12.78; Found: C, 73.97; H, 6.12;
N, 12.85%.
Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C,
72.19; H, 5.37; N, 10.48%.
1e: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.05 (s, 1H), 7.86 (d,
2H, J = 8.5 Hz), 7.36 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 7.30 (d, 2H,
J = 8.5 Hz), 6.95 (t, 1H, J = 2.0 Hz), 6.20 (dd, 1H, J = 2.0 Hz and J =
4.5 Hz), 3.98 (s, 3H), 2.90−2.85 (m, 1H), 1.23 (d, 6H, J = 7.0 Hz).
Anal. Calcd for C18H18N2O: C, 77.67; H, 6.52; N, 10.06. Found: C,
77.69; H, 6.43; N, 10.08%.
4g: 1H NMR (500 MHz, CDCl3): δ 7.95−7.90 (m, 2H), 7.31 (t, 1H,
J = 7.5 Hz), 7.23 (s, 1H), 7.20 (d, 1H, J = 8.0 Hz), 7.12 (t, 1H, J = 8.0
Hz), 6.86 (s, 1H), 6.76 (d, 1H, J = 8.0 Hz), 6.69 (s, 1H), 6.11 (t, 1H,
J = 2.5 Hz), 5.67 (dd, 1H, J = 4.5 Hz and J = 2.5 Hz), 5.39 (dd, 1H,
J = 9.5 Hz and J = 5.5 Hz), 3.75−3.69 (m, 4H), 3.55−3.50 (m, 1H),
2.32 (s, 3H), 2.18 (s, 3H), 2.05 (s, 3H). IR(KBr): 3310, 3108, 2857,
2360, 1749, 1614, 1465 cm−1. Anal. Calcd for C27H26N4O2: C, 73.95;
H, 5.98; N, 12.78; Found: C, 73.87; H, 5.91; N, 12.75%.
1f: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.04 (s, 1H), 7.79 (d,
1H, J = 8.0 Hz), 7.76 (s, 1H), 7.35 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz),
7.26 (d, 1H, J = 7.5 Hz), 6.95 (t, 1H, J = 1.5 Hz), 6.21 (dd, 1H, J = 2.5
Hz and J = 4.5 Hz), 3.97 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H). Anal.
Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C, 77.19;
H, 6.19; N, 10.48%.
4h: 1H NMR (500 MHz, CDCl3): δ 8.50 (s, 1H), 8.16 (d, 1H, J = 7.5
Hz), 7.99−7.96 (m, 2H), 7.54 (t, 1H, J = 8.0 Hz), 7.34−7.31 (m, 1H),
7.25−7.23 (m, 1H), 7.18 (s, 1H), 6.70 (s, 1H), 6.66 (d, 1H, J = 7.5 Hz),
6.17(dd, 1H, J = 4.5 Hz and J = 2.5 Hz), 5.66 (dd, 1H, J = 4.5 Hz and
J = 2.5 Hz), 5.56 (dd, 1H, J = 10.0 Hz and J = 5.5 Hz), 3.83 (t, 1H,
J = 9.5 Hz), 3.80 (s, 3H), 3.70 (dd, 1H, J = 9.5 Hz and J = 6.0 Hz),
2.25 (s, 3H). IR(KBr): 3319, 3107, 2957, 2863, 2240, 1730, 1615,
1520, 1468 cm−1. Anal. Calcd for C25H21N5O4: C, 65.93; H, 4.65;
N, 15.38; Found: C, 65.88; H, 4.75; N, 15.40%.
1g: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.36 (s, 1H), 8.20 (d,
1H, J = 8.0 Hz), 7.36 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 7.15 (d, 1H,
J = 8.0 Hz), 7.15 (s, 1H), 6.96 (t, 1H, J = 1.5 Hz), 6.22 (dd, 1H, J = 2.5
Hz and J = 4.5 Hz), 3.99 (s, 3H), 2.40 (s, 3H), 2.38 (s, 3H). Anal.
Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C, 77.32;
H, 6.09; N, 10.53%.
1h: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.70 (s, 1H), 8.41 (d,
1H, J = 8.0 Hz), 8.39−8.37 (m, 1H), 8.11 (s, 1H), 7.73 (t, 1H, J = 8.0
Hz), 7.40 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 7.01 (t, 1H, J = 1.5 Hz),
6.26 (dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 4.00 (s, 3H). Anal. Calcd
for C15H11N3O3: C, 64.05; H, 3.94; N, 14.94. Found: C, 64.09; H, 3.87;
N, 14.93%.
4i: 1H NMR (500 MHz, CDCl3): δ 8.23 (s, 2H), 7.99 (s, 1H), 7.78
(s, 2H), 7.32−7.29 (m, 1H), 7.26−7.14 (m, 2H), 6.70 (t, 1H, J = 2.0
Hz), 6.66 (d, 1H, J = 7.5 Hz), 6.18 (dd, 1H, J = 5.0 Hz and J = 2.0 Hz),
5.66 (dd, 1H, J = 4.0 Hz and J = 2.0 Hz), 5.56 (dd, 1H, J = 10.0 Hz
and J = 6.0 Hz), 3.81 (t, 1H, J = 9.5 Hz), 3.79 (s, 3H), 3.68 (dd, 1H,
J = 10.0 Hz and J = 6.0 Hz), 2.24 (s, 3H). IR(KBr): 3325, 3092, 2972,
2867, 2235, 1724, 1618, 1523, 1470 cm−1.Anal. Calcd for C25H21N5O4:
C, 65.93; H, 4.65; N, 15.38; Found: C, 65.95; H, 4.71; N, 15.47%.
4j: 1H NMR (500 MHz, CDCl3): δ 8.00 (s, 1H), 7.85 (s, 1H), 7.44
(dd, 1H, J = 8.5 Hz and J = 2.0 Hz), 7.34−7.31 (m, 1H), 7.26 (s, 1H),
7.12 (t, 1H, J = 7.5 Hz), 6.76 (d, 1H, J = 8.0 Hz), 6.74 (s, 1H), 6.24
(dd, 1H, J = 4.5 Hz and J = 2.5 Hz), 5.73 (dd, 1H, J = 4.5 Hz and J =
2.5 Hz), 5.66 (dd, 1H, J = 9.5 Hz and J = 5.0 Hz), 5.30 (s, 1H), 3.81
(t, 1H, J = 9.5 Hz), 3.77(s, 3H), 3.47 (dd, 1H, J = 9.5 Hz and J = 5.0
Hz), 2.18 (s, 3H). IR(KBr): 3318, 3106, 2970, 2862, 2359, 1738,
1617, 1470 cm−1. Anal. Calcd for C25H20N4O2Cl2: C, 62.64; H, 4.21;
N, 11.69; Found: C, 62.69; H, 4.16; N, 11.77%.
1
1i: H NMR (500 MHz, DMSO-d6): δ (ppm) 8.36−8.34 (m, 2H),
8.14−8.10 (m, 3H), 7.40 (dd, 1H, J = 1.5 Hz and J = 4.5 Hz), 7.02
(t, 1H, J = 1.5 Hz), 6.26 (dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 4.00 (s,
3H). Anal. Calcd for C15H11N3O3: C, 64.05; H, 3.94; N, 14.94. Found:
C, 64.11; H, 3.95; N, 14.87%.
1j: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.36 (s, 1H), 8.20 (d,
1H, J = 8.5 Hz), 7.53 (d, 1H, J = 2.0 Hz), 7.41 (d, 1H, J = 8.5 Hz), 7.34
(dd, 1H, J = 1.5 Hz and J = 4.5 Hz), 7.00 (t, 1H, J = 2.0 Hz), 6.24 (dd,
1H, J = 2.5 Hz and J = 4.0 Hz), 3.99 (s, 3H). Anal. Calcd for
C15H10Cl2N2O: C, 59.04; H, 3.30; N, 9.18. Found: C, 59.09; H, 3.21;
N, 9.23%.
1k: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.40 (s, 1H), 8.25 (s,
1H), 8.20 (dd, 1H, J = 1.5 Hz and J = 8.5 Hz), 7.96−7.93 (m, 2H), 7.89
(d, 1H, J = 8.0 Hz), 7.62 (t, 1H, J = 8.0 Hz), 7.56 (t, 1H, J = 8.0 Hz),
7.41 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 6.98 (t, 1H, J = 1.5 Hz), 6.24
(dd, 1H, J = 2.5 Hz and J = 4.5 Hz), 4.00 (s, 3H). Anal. Calcd
for C19H14N2O: C, 79.70; H, 4.93; N, 9.78. Found: C, 79.79; H, 4.87;
N, 9.69%.
4k: 1H NMR (500 MHz, CDCl3): δ 8.14−8.04 (m, 2H), 7.85−7.81
(m, 3H), 7.76 (dd, 1H, J = 8.5 Hz and J = 2.0 Hz), 7.45 (dd, 2H, J =
6.5 Hz and J = 3.0 Hz), 7.33−7.29 (m, 1H), 7.26−7.19 (m, 2H), 6.68
(d, 1H, J = 7.5 Hz), 6.64 (t, 1H, J = 1.5 Hz), 6.13 (dd, 1H, J = 4.5 Hz
and J = 1.5 Hz), 5.58−5.53 (m, 2H), 3.86 (d, 2H, J = 8.5 Hz), 3.78
(s, 3H), 2.28 (s, 3H). IR(KBr): 3288, 3107, 2861, 2360, 1742, 1613,
1469, 1404, 1362 cm−1. Anal. Calcd for C29H24N4O2: C, 75.63; H, 5.25;
N, 12.17; Found: C, 75.66; H, 5.39; N, 12.13%.
This work was financially supported by the research founda-
tion of Hebei University of Science and Technology.
Synthesis of 1a–k: A mixture of 5 (0.45 g, 3 mmol), 6 (3 mmol) and
glycol monomethyl ether (10 mL) were refluxed for 2 h (the progress
was monitored by TLC). After completion of the reaction, the mixture
was allowed to cool to room temperature and the crude products
were precipitated. The crude product was chromatographed on
silica gel (200–300 mesh) using a mixture of petroleum ether and
dichloromethane as eluent to afford the pure product 1a–k.
Received 27 November 2010; accepted 4 January 2011
Paper 1000449 doi: 10.3184/174751911X556846
Published online: 10 February 2011
1a: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.09 (s, 1H), 8.00−7.98
(m, 2H), 7.54−7.49 (m, 3H), 7.37 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz),
6.97 (d, 1H, J = 1.5 Hz), 6.23 (dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 3.98
(s, 3H). Anal. Calcd for C15H12N2O: C, 76.25; H, 5.12; N, 11.86.
Found: C, 76.32; H, 5.09; N, 11.91%.
References
1
O. Tsuge and S. Kanemasa, Advances in heterocyclic chemistry, Vol. 45,
ed. A.R. Katritzky, Academic Press, San Diego, 1989, p.231.
R. Grigg and V. Sridharan, Advances in cycloaddition, Vol.3, ed. D.P.
Curran, Jai Press, London, 1993, p161.
2
3
4
5
G. Pandey, P. Banerjee and S.R. Gadre, Chem. Rev., 2006, 106, 4484.
S. Rehn, J. Bergman and B. Stensland, Eur. J. Org. Chem., 2004, 413.
P.R. Sebahar, H. Osafa, T. Usui and R.M. Williams, Tetrahedron, 2002, 58,
6311.
1b: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.07 (s, 1H), 7.90 (d,
2H, J = 8.5 Hz), 7.36 (dd, 1H, J = 1.5 Hz and J = 4.5 Hz), 7.31 (d, 2H,
J = 8.5 Hz), 6.95 (t, 1H, J = 2.0 Hz), 6.20 (dd, 1H, J = 2.0 Hz and
J = 4.5 Hz), 3.98 (s, 3H), 2.44 (s, 3H). Anal. Calcd for C16H14N2O:
C, 76.78; H, 5.64; N, 11.19. Found: C, 76.72; H, 5.69; N, 11.10%.
1c: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.07 (s, 1H), 7.99 (dd,
2H, J = 1.5 Hz and J = 7.5 Hz), 7.37 (dd, 1H, J = 1.5 Hz and J = 4.0
Hz), 6.89 (t, 1H, J = 1.5 Hz), 6.71 (d, 2H, J = 7.5 Hz), 6.19 (dd, 1H,
J = 2.5 Hz and J = 4.0 Hz), 3.96 (s, 3H), 3.11 (s, 6H). Anal. Calcd for
C17H17N3O: C, 73.10; H, 6.13; N, 15.04. Found: C, 73.19; H, 6.17; N,
15.08%.
6
7
8
9
O. Lukoyanova, C.M. Cardona, M. Altable, S. Filippone, A.M. Domenech,
N. Martin and L. Echegoyen, Angew. Chem., 2006, 118, 7590.
M.S. Chande, R.S. Verma and P.A. Barve, Eur. J. Med. Chem., 2005, 40,
1143.
D. Sriram, P. Yogeeswari and K. Madhu, Bioorg. Med. Chem. Lett., 2006,
16, 876.
M.A. Abou-Gharbia and P.H. Doukas, Heterocycles, 1979, 12, 637.
10 M.J. Kornet and A.P. Thio, J. Med. Chem., 1976, 19, 892.
11 C. Marti and E. Carreira, Eur. J. Org.Chem., 2003, 2209.
12 N.V. Lakshmi, P. Thirumurugan and P. Peruml, Tetrahedron Lett., 2010,
51, 1064.
13 L.J. Geng, G.L. Feng and J.G. Yu, J. Chem. Res., 2010, 34, 333.
14 L.J. Geng, G.L. Feng and J.G. Yu, J. Chem. Res., 2010, 34, 565.
1d: 1H NMR (500 MHz, DMSO-d6): δ (ppm) 8.56 (s, 1H), 8.30 (dd,
1H, J = 1.5 Hz and J = 8.0 Hz), 7.52−7.48 (m, 1H), 7.31 (dd, 1H, J =
1.5 Hz and J = 4.0 Hz), 7.08 (t, 1H, J = 7.5 Hz), 6.97−6.95 (m, 2H),
6.21 (dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 3.98 (s, 3H), 3.89 (s, 3H).

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