C2-functionalization of 1-substituted imidazoles with aldehydes and electron-deficient acetylenes: A novel three-component reaction

Article abstract of DOI:10.1002/ejoc.200901397

A novel three-component reaction between 1-substituted imidazoles, aldehydes, and electron-deficient acetylenes proceeds under mild conditions (20-25 °C, no catalyst, no solvent) to form, an unknown family of C2-functionalized imidazoles in up to 74 % yield, the function constituting a pushpull combination of enol ether and acrylic moieties. In the case of cyanophenylacetylene, the function is built up stereospecifically to have the (Z) configuration. The interaction presumably occurs via zwitterion and carbene intermediates. The results contribute to basic imidazole and acetylene chemistry and open a shortcut to promising drug candidates.

Full text of DOI:10.1002/ejoc.200901397

FULL PAPER
DOI: 10.1002/ejoc.200901397
C2-Functionalization of 1-Substituted Imidazoles with Aldehydes and
Electron-Deficient Acetylenes: A Novel Three-Component Reaction
Boris A. Trofimov,*[a] Ludmila V. Andriyankova,[a] Kseniya V. Belyaeva,[a]
Anastasiya G. Mal’kina,[a] Lina P. Nikitina,[a] Andrei V. Afonin,[a] and Igor’ A. Ushakov[a]
Keywords: Nitrogen heterocycles / Electron-deficient compounds / Aldehydes / Multicomponent reactions / Alkynes
A novel three-component reaction between 1-substituted
imidazoles, aldehydes, and electron-deficient acetylenes
proceeds under mild conditions (20–25 °C, no catalyst, no sol-
vent) to form an unknown family of C2-functionalized imid-
azoles in up to 74% yield, the function constituting a push–
pull combination of enol ether and acrylic moieties. In the
case of cyanophenylacetylene, the function is built up stereo-
specifically to have the (Z) configuration. The interaction pre-
sumably occurs via zwitterion and carbene intermediates.
The results contribute to basic imidazole and acetylene
chemistry and open a shortcut to promising drug candidates.
Recently, we reported the unprecedented direct C2-
vinylation[9a,9b] and 1,3-butadienylation[9c] of 1-substituted
imidazoles with cyanophenylacetylene that proceeds via
zwitterionic and carbene intermediates involving N3ǞC2
migration of the functionalized vinyl or 1,3-butadienyl moi-
eties. Because cyanophenylacetylene is readily available
from bromophenylacetylene and copper cyanide,[10] these
reactions are of general character and significantly contrib-
ute to the chemistry and application of 2-functionalized
imidazoles. To extend these findings, we tried to capture
the intermediate zwitterions generated from 1-substituted
imidazole and electron-withdrawing acetylenes by an ap-
propriate electrophile as a third component.
Introduction
The imidazole ring is a frequent structural unit found in
numerous natural products and biologically active com-
pounds. Therefore, the search for new methods of function-
alization of the imidazole nucleus, particularly C2-alkyl-
ation is considered as a standing challenge in organic syn-
thesis.[1] Commonly, C2-alkylation of the imidazole ring
starts with lithiation followed by reaction with electro-
philes.[1a,2] Some 2-substituted imidazoles have been synthe-
sized from 1-alkyl-2-trialkylstannylimidazoles and electro-
philes, the former being prepared from the corresponding
derivative.[1b,3] 2-Acylimidazoles have been prepared from
1-alkylimidazoles and acyl halides in the presence of
amines, the corresponding imidazolium ylides being sug-
gested as the reaction intermediates.[1d,4] Later, imidazolium
ylides were reported to react with various electrophiles to
yield C2-substituted imidazoles.[5] To introduce substituents
at the C2 position of imidazoles, palladium- and copper-
catalyzed[6] cross-couplings were employed; for example, 1-
arylimidazole was treated with bromobenzene in the pres-
ence of palladium complexes to deliver 2-phenylimid-
azoles.[6c] In the presence of [Ir4(CO)12] and diethylmethyl-
silane, 1-methylimidazole was treated (boiling toluene) with
n-hexanal to afford 2-[1-(diethylmethylsiloxy)hexyl]-1-
methyl-1H-imidazole in 35% yield.[7] Nair et al.[8] published
interesting results on multicomponent interactions of imid-
azole carbenes with dimethylacetylenedicarboxylate and al-
dehydes to furnish dihydroimidazoles bridged (through the
double bond) by their C2 position with a functionalized
dihydrofuranone moiety.
Results and Discussion
In this paper, we report on a new three-component reac-
tion between 1-substituted imidazoles 1a–e, electron-de-
ficient acetylenes 2a,b, and aldehydes 3a–d, which leads to
a novel class of imidazoles substituted at the C2 position
with a function built up from enol ether and acrylic moie-
ties.
On the basis of experimental data[9] indicating the forma-
tion of intermediate zwitterion A from 1-substitutted imid-
azoles and electron-withdrawing acetylenes, we expected
that in the presence of aldehydes the reaction sequence de-
picted in Scheme 1 should take place.
As follows from Scheme 1, zwitterion A is to be captured
by aldehydes to give zwitterion B, which then undergoes
ring closure at the 2-position to furnish imidazo-1,3-oxaz-
ine C.
[a] A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences,
In reality, the above three components (1a–e, 2a,b, and
3a–d) reacted together in another, entirely unpredictable
way: instead of imidazo-1,3-oxazine C, imidazoles substi-
1 Favorsky Str., 664033 Irkutsk, Russian Federation
Fax: +395-2-41-93-46
E-mail: boris_trofimov@irioch.irk.ru
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Novel Three-Component Reaction
respectively). Meanwhile, the reaction of 1-vinylimidazole
(1e), acetylene 2b, and aldehyde 3a took 13 d, which results
from the electron-withdrawing effect of the N-vinyl group
that decreases the basicity at the N3 atom in imidazole 1e.
The stereochemistry of the reaction is determined by the
acetylene structure: with acetylene 2a the function formed
has both (E) and (Z) configurations (in a ratio of ca. 2–
4:1), whereas in the case of acetylene 2b the process is regio-
and stereospecific to afford the (Z) configuration only.
Obtained enol ethers 4a–n are yellow or light-brown oils
soluble in conventional organic solvents. Their structures
were proved by NMR (1H, 13C) spectroscopy by using 2D
techniques (COSY, NOESY, HMBC, HSQC).
In the 1H NMR spectra of enol ethers 4a–c, two doublets
of olefinic protons (8-H, 9-H) are observed for the (E) iso-
mers at δ = 7.52–7.66 (8-H) and 5.34–5.49 (9-H) ppm and
for the (Z) isomers at δ = 6.60–6.72 (8-H) and 4.83–4.93 (9-
Scheme 1. The expected products of the three-component reaction
between 1-substitutted imidazoles, electron-withdrawing acetylenes,
and aldehydes.
1
H) ppm. In the H NMR spectra of enol ethers 4d–n, sing-
lets of the vinyl protons (9-H) are observed at δ = 4.91–
5.09 ppm. The vinyl moiety of enol ethers 4d–n manifests
itself in the 13C NMR spectra by signals in the region δ =
169.1–171.5 (C-8) and 75.5–78.0 (C-9) ppm. The nitrile C-
atom resonates at δ = 116.2–116.9 ppm. The large difference
between chemical shifts of the olefinic C-8 and C-9 carbon
atoms (δ ≈ 93 ppm) is explained by the high polarization of
the double bond caused by both the electron-withdrawing
effect of the cyano group and the electron-donating p–π
conjugation between the alkoxy group and the double bond
common for vinyl ethers[11] (push–pull combination of the
R–O and CN substituents).
tuted at the 2-position with functionalized ethenyl moieties
4a–n were isolated in 31–74% yield as the only products
(Table 1).
Table 1. Formation of functionalized ethenyl moieties 4a–n from 1-
substituted imidazoles 1, electron-deficient acetylenes 2, and alde-
hydes 3.
According to the NOESY spectra, products 4d–n are (Z)
isomers: cross-peaks between the olefinic 9-H proton and
the ortho protons of the phenyl groups are observed (Fig-
ure 1).
Product R1
R2
R3
R4
Isolated
yield [%]
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
Me
Me
Me
Me
Me
Me
Et
Et
Et
iBu
iBu
iBu
Bn
H
H
H
CO2Me
CO2Me
CO2Me
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
Me
nPr
Ph
41
53
74
58
43
31
49
54
54
62
59
57
41
62
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
nPr
nBu
Me
nPr
nBu
Me
nPr
nBu
Me
Me
Figure 1. Cross-peaks in the 2D NOESY spectra of enol ethers
4d–n.
1
In H, 13C and 15N NMR spectra of enol ethers 4a–n,
the following signals of the imidazole ring are present: 4-H,
5-H; C-2, C-4, C-5; and N-1, N-3. The C-2 atom lacks pro-
tons, which confirms the location of the substituent at the
HC=CH2 Ph
The reaction conditions are mild: room temperature and 2-position of the imidazole ring. In the 13C NMR spectra
no catalyst and solvent. Duration of the reaction and the of compounds 4a–n, the signals of C-4 and C-5 have similar
product yields depend on the structure of the reactants. For values as the starting imidazoles, whereas the C-2 signal is
example, the reaction of imidazole 1a, methyl propiolate shifted downfield (from δ = 136–137 to 143–145 ppm) by
(2a), and benzaldehyde (3d) was complete within 1.5 h to the negative inductive effect of the substituents. As ex-
furnish enol ether 4c (74% yield), whereas the reaction be- pected, in the 15N NMR spectra of compounds 4d,e, the N-
tween the same imidazole, acetylenes 2a,b, and aldehyde 3a 1 and N-3 nuclei resonate at different regions from δ = –223
required 24 h to give products 4a and 4d (41 and 58% yield, to –225 and from δ = –120 to –129 ppm, respectively.
Eur. J. Org. Chem. 2010, 1772–1777
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B. A. Trofimov et al.
FULL PAPER
The IR spectra of products 4d–n are in agreement with
their structure: the characteristic bands of starting com-
pounds (1713–1723 cm–1 for aldehyde HC=O, 2257–
2275 cm–1 for CN in acetylene 2b) disappear, and instead,
the bands at 2214–2218 cm–1 belonging to the CN group at
the double bond and the νC=C absorption band at 1612–
1651 cm–1 are observed; the very strong absorption band
in the region 1059–1096 cm–1 is attributed to the C–O–C
bonds.
Scheme 3. Possible conversion of zwitterion E into product 4 by an
addition–elimination sequence.
Apparently, zwitterion A reacts with traces amount of
water to furnish imidazolium derivative AЈ, which is depro-
–
tonated under the action of the OH anion to give carbene
sary participation of protogenic species (e.g., water) as a
catalyst, concentration of which under solvent-free condi-
tions is negligible.
Indeed, in the presence of water, the two-component re-
action of imidazole 1a and acetylene 2b (molar ratio 1a/2b/
H2O = 1:1:4, room temperature, 24 h) delivers stereoselec-
tively the C2-vinylation product (Z)-2-(2-cyano-1-phenyl-
ethenyl)-1-methylimidazole (5) in 30% yield (Scheme 4).
D. Carbene D then reacts with the aldehyde to afford zwit-
terion E, which further rearranges into final products 4a–n
(Scheme 2).
Scheme 4. Direct C2-vinylation of imidazole 1a with acetylene 2b
in the presence of water.
A
similar C2-vinylation of 1-methylimidazole with
acetylene 2b was recently reported[9a,9b] under solvent-free
conditions (without special precautions against trace
amounts of water). In this connection, it is worthwhile to
note that in the reaction mixtures of the three-component
functionalization, minor amounts (1–5%) of C2-vinylation
products are always detectable (1H NMR spectroscopy).
Scheme 2. Tentative reaction sequence for the formation of prod-
ucts 4a–n.
A similar insertion of imidazoline carbene of type D into
the C=O bond of aldehydes has been reported by Hlasta et
al.[5] and Nair et al.[8]
The conversion of intermediate E into products 4a–n in-
volves electron-pair transfer from Cβ of the acrylic moiety
to N-3, accompanied by Cβ–O bond formation between the
Conclusions
In summary, a facile (room temperature, noncatalytic,
emerging carbocation at the Cβ carbon and the O-centered solvent-free), three-component reaction between 1-substi-
anion. tuted imidazoles, electron-deficient acetylenes, and alde-
Another mode of transformation of zwitterion E to the hydes has been discovered. The reaction leads to hitherto
final product could involve intramolecular nucleophilic ad- unknown C2-functionalized imidazoles (in up to 74% yield)
dition of an oxygen anion to the electrophilic double bond functionalized with substituents representing a combination
to give zwitterion EЈ, which then delivers the final product of enol ether and acrylic moieties. In the case of cyanophen-
by intramolecular imidazole elimination (Scheme 3).
ylacetylene, the reaction is stereospecific to secure exclu-
In terms of a higher electrophilicity of some electron- sively the (Z) configuration. Notably, different combina-
deficient acetylenes over aldehydes, this route seems to be tions of 1-substituted imidazoles with aldehydes obey the
also reasonable. A shortcoming of this scheme is the neces- reaction, and such reactive functions as enol ether, acrylate,
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Novel Three-Component Reaction
1495, 1438, 1415, 1330, 1284, 1232, 1192, 1139, 1060, 1028, 957,
nitrile, and styrene groups are tolerant towards the reaction
conditions. The reaction has all prerequisites to occupy an
important place in imidazole and acetylene chemistry, par-
ticularly for drug design.
838, 802, 755, 729, 661 cm–1. (E)-4b: 1H NMR (400.13 MHz,
3
CDCl3): δ = 7.52 (d, JH8,H9 = 12.5 Hz, 1 H, 8-H), 6.95 (s, 1 H, 4-
H), 6.86 (s, 1 H, 5-H), 5.34 (d, 1 H, 9-H), 5.10 (t, 3JH6,CH = 6.7 Hz,
2
1 H, 6-H), 3.68 (s, 3 H, O-CH3), 3.66 (s, 3 H, N-CH3), 2.09–2.01
(m, 2 H, C6-CH2-), 1.47–1.44 (m, 2 H, C6-CH2-CH2-), 0.95–0.92
(m, 3 H, C6-CH2-CH2-CH3) ppm. 13C NMR (100.62 MHz,
CDCl3): δ = 167.6 (C=O), 160.1 (C-8), 144.3 (C-2), 127.3 (C-4),
122.5 (C-5), 98.4 (C-9), 77.3 (C-6), 50.7 (O-CH3), 34.9 (N-CH3),
32.8 (C6-CH2-), 18.4 (C6-CH2-CH2-CH3), 13.3 (C6-CH2-CH2-)
Experimental Section
General: IR spectra were recorded with a Bruker IFS 25 instru-
ment. NMR spectra were obtained with a Bruker DPX-400 spec-
trometer with HMDS as an internal standard. 1-Substituted imid-
azoles 1a–e were prepared according to literature procedures.[12]
Methyl propiolate (2a) is a commercial reagent (“Merck”), and cya-
nophenylacetylene (2b) was obtained by a literature procedure.[10]
Column and thin-layer chromatography were carried out on neutral
Al2O3 with chloroform/benzene/ethanol, 20:4:1 as eluent. The reac-
tion was monitored by the disappearance of absorption bands of
initial acetylenes 2a,b in the reaction mixture (IR spectroscopy).
For labeling of NMR assignments, see Figure 2.
1
ppm. (Z)-4b: H NMR (400.13 MHz, CDCl3): δ = 6.91 (s, 1 H, 4-
3
H), 6.79 (s, 1 H, 5-H), 6.60 (d, JH8,H9 = 7.0 Hz, 1 H, 8-H), 5.13
3
(t, JH6,CH = 6.7 Hz, 1 H, 6-H), 4.83 (d, 1 H, 9-H), 3.64 (s, 3 H,
2
N-CH3), 3.64 (s, 3 H, O-CH3), 2.09–2.01 (m, 2 H, C6-CH2-), 1.47–
1.44 (m, 2 H, C6-CH2-CH2-), 0.95–0.92 (m, 3 H, C6-CH2-CH2-
CH3) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 165.1 (C=O),
156.1 (C-8), 144.5 (C-2), 127.0 (C-4), 122.8 (C-5), 96.6 (C-9), 79.3
(C-6), 50.7 (O-CH3), 34.9 (N-CH3), 32.8 (C6-CH2-), 18.4 (C6-CH2-
CH2-CH3), 13.3 (C6-CH2-CH2-) ppm. C12H18N2O3 (238.28): calcd.
C 60.49, H 7.61, N 11.76; found C 60.03, H 7.32, N 11.25.
Methyl (E+Z)-3-[(1-Methyl-1H-imidazol-2-yl)(phenyl)methoxy]-2-
propenoate (4c): Analogously, from methyl propiolate (2a; 0.084 g,
1 mmol), benzaldehyde (3d; 0.106 g, 1 mmol), and 1-methylimid-
azole (1a; 0.082 g, 1 mmol) (20–25 °C, 1.5 h) enol ether 4c (0.202 g,
74%) was obtained as a yellow oil. (E)-4c/(Z)-4c = 80:20. IR
(microlayer): ν = 3532, 3386, 3138, 3111, 3065, 3029, 2997, 2952,
˜
2848, 1713, 1645, 1625, 1496, 1453, 1438, 1414, 1333, 1310, 1282,
1192, 1177, 1135, 1080, 1049, 1030, 1002, 968, 913, 839, 804, 755,
732, 698, 667, 640, 523 cm–1. (E)-4c: 1H NMR (400.13 MHz,
3
CDCl3): δ = 7.35–7.30 (m, 5 H, Ph), 7.66 (d, JH8,H9 = 12.5 Hz, 1
H, 8-H), 6.95 (s, 1 H, 4-H), 6.81 (s, 1 H, 5-H), 6.27 (s, 1 H, 6-H),
5.49 (d, 1 H, 9-H), 3.57 (s, 3 H, O-CH3), 3.37 (s, 3 H, N-CH3)
ppm. 13C NMR (100.62 MHz, CDCl3): δ = 167.0 (C=O), 160.0 (C-
8), 143.6 (C-2), 135.8 (Ci, Ph), 128.2 (Cm, Ph), 127.9 (Cp, Ph), 127.2
(C-4), 125.5 (Co, Ph), 122.7 (C-5), 99.0 (C-9), 78.2 (C-6), 50.5 (O-
CH3), 32.7 (N-CH3) ppm. (Z)-4c: 1H NMR (400.13 MHz, CDCl3):
δ = 7.35–7.30 (m, 5 H, Ph), 6.93 (s, 1 H, 4-H), 6.80 (s, 1 H, 5-H),
Figure 2. Labeling of hydrogen and carbon atoms in compounds
4a–n used for NMR assignments.
Methyl (E+Z)-3-[1-(1-Methyl-1H-imidazol-2-yl)ethoxy]-2-propeno-
ate (4a): To a mixture of methyl propiolate (2a; 0.084 g, 1 mmol)
and ethanal (3a; 0.132 g, 3 mmol) was added 1-methylimidazole
(1a; 0.082 g, 1 mmol). The mixture was stirred at 20–25 °C for 24 h.
Column chromatography afforded enol ether 4a (0.087 g, 41%) as
3
6.72 (d, JH8,H9 = 7.0 Hz, 1 H, 8-H), 6.27 (s, 1 H, 6-H), 4.93 (d, 1
H, 9-H), 3.65 (s, 3 H, O-CH3), 3.44 (s, 3 H, N-CH3) ppm. 13C
NMR (100.62 MHz, CDCl3): δ = 164.7 (C=O), 156.4 (C-8), 144.1
(C-2), 136.2 (Ci, Ph), 128.2 (Cm, Ph), 127.7 (Cp, Ph), 126.8 (C-4),
125.2 (Co, Ph), 123.1 (C-5), 97.2 (C-9), 80.8 (C-6), 50.3 (O-CH3),
32.8 (N-CH3) ppm. C15H16N2O3 (272.30): calcd. C 66.16, H 5.92,
N 10.29; found C 65.84, H 5.70, N 9.99.
a yellow oil. (E)-4a/(Z)-4a = 65:35. IR (microlayer): ν = 3576, 3396,
˜
3138, 3112, 2990, 2952, 2891, 1714, 1644, 1623, 1497, 1438, 1416,
1380, 1330, 1284, 1221, 1194, 1139, 1117, 1067, 1042, 962, 929, 834,
757, 703, 664, 504 cm–1. (E)-4a: 1H NMR (400.13 MHz, CDCl3): δ
3
= 7.57 (d, JH8,H9 = 12.5 Hz, 1 H, 8-H), 6.95 (s, 1 H, 4-H), 6.87 (s,
3
1 H, 5-H), 5.36 (d, 1 H, 9-H), 5.26 (q, JH6,CH = 6.7 Hz, 1 H, 6-
(Z)-3-[(1-Methyl-1H-imidazol-2-yl)ethoxy]-3-phenyl-2-propeneni-
trile (4d): Analogously, from acetylene 2b (0.127 g, 1 mmol),
ethanal (3a; 0.132 g, 3 mmol), and 1-methylimidazole (1a; 0.082 g,
1 mmol) (20–25 °C, 24 h) enol ether 4d (0.148 g, 58%) was obtained
3
H), 3.65 (s, 3 H, N-CH3), 3.63 (s, 3 H, O-CH3), 1.74 (d, 3 H, C6-
CH3) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 167.8 (C=O),
159.9 (C-8), 144.9 (C-2), 127.5 (C-4), 122.7 (C-5), 98.7 (C-9), 73.0
(C-6), 51.0 (O-CH3), 32.9 (N-CH3), 18.4 (C6-CH3) ppm. (Z)-4a: 1H
NMR (400.13 MHz, CDCl3): δ = 6.93 (s, 1 H, 4-H), 6.88 (s, 1 H,
as a light-brown oil. IR (microlayer): ν = 3066, 2987, 2937, 2215,
˜
1614, 1575, 1493, 1448, 1413, 1377, 1346, 1307, 1283, 1258, 1186,
1150, 1114, 1085, 1063, 1041, 1026, 1009, 979, 920, 897, 848, 762,
698, 665, 519 cm–1. 1H NMR (400.13 MHz, CDCl3): δ = 7.50–7.40
3
3
5-H), 6.60 (d, JH8,H9 = 7.0 Hz, 1 H, 8-H), 5.33 (q, JH6,CH
=
3
6.7 Hz, 1 H, 6-H), 4.85 (d, 1 H, 9-H), 3.65 (s, 3 H, O-CH3), 3.64 (s,
3 H, N-CH3), 1.76 (d, 3 H, C6-CH3) ppm. 13C NMR (100.62 MHz,
CDCl3): δ = 165.2 (C=O), 155.5 (C-8), 144.7 (C-2), 127.2 (C-4),
123.0 (C-5), 97.2 (C-9), 74.9 (C-6), 50.7 (O-CH3), 33.1 (N-CH3),
18.5 (C6-CH3) ppm. C10H14N2O3 (210.23): calcd. C 57.13, H 6.71,
N 13.32; found C 56.82, H 6.45, N 13.00.
(m, 5 H, Ph), 6.95 (s, 1 H, 4-H), 6.88 (s, 1 H, 5-H), 5.85 (q, 3JH6,CH
3
= 6.4 Hz, 1 H, 6-H), 5.02 (s, 1 H, 9-H), 3.83 (s, 3 H, N-CH3), 1.77
(s, 3 H, C6-CH3) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 170.5
(C-8), 145.3 (C-2), 133.1 (Ci, Ph), 131.5 (Cp, Ph), 129.0 (Cm, Ph)
127.7 (C-4), 127.1 (Co, Ph), 122.9 (C-5), 116.8 (C-10, CN), 77.1
(C-9), 73.0 (C-6), 43.6 (N-CH3), 19.1 (C6-CH3) ppm. 15N NMR
(40.55 MHz, CDCl3): δ = –124.7 (CN-10), –129.4 (N-3), –224.9 (N-
1) ppm. C15H15N3O (253.30): calcd. C 71.13, H 5.97, N 16.59;
found C 71.40, H 5.80, N 16.85.
Methyl (E+Z)-3-[1-(1-Methyl-1H-imidazol-2-yl)butoxy]-2-propeno-
ate (4b): Analogously, from methyl propiolate (2a; 0.084 g,
1 mmol), n-butanal (3b; 0.072 g, 1 mmol), and 1-methylimidazole
(1a; 0.082 g, 1 mmol) (20–25 °C, 4 h) enol ether 4b (0.126 g, 53%)
was obtained as a yellow oil. (E)-4b/(Z)-4b = 75:25. IR (micro-
(Z)-3-[(1-Methyl-1H-imidazol-2-yl)butoxy]-3-phenyl-2-propeneni-
trile (4e): Analogously, from acetylene 2b (0.127 g, 1 mmol), n-but-
layer): ν = 3569, 3404, 3136, 3110, 2960, 2875, 1714, 1643, 1624,
˜
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B. A. Trofimov et al.
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anal (3b; 0.072 g, 1 mmol), and 1-methylimidazole (1a; 0.082 g,
1 mmol) (20–25 °C, 24 h) enol ether 4e (0.122 g, 43%) was obtained
3 JH , H = 7.1 Hz, 3 H, C6 -(CH2 )2 -CH3 ] ppm. 1 3 C NMR
(100.62 MHz, CDCl3): δ = 171.2 (C-8), 143.9 (C-2), 133.8 (Ci, Ph),
131.1 (Cp, Ph), 128.9 (Cm, Ph), 127.7 (C-4), 127.0 (Co, Ph), 119.9
(C-5), 116.7 (C-10, CN), 77.9 (C-9), 77.1 (C-6), 40.6 (N-CH2-), 35.4
(C6-CH2-), 18.6 (C6-CH2-CH2-), 16.3 (N-CH2-CH3), 13.5 [C6-
(CH)2-CH3] ppm. C18H21N3O (295.38): calcd. C 73.19, H 7.17, N
14.23; found C 72.75, H 6.90, N 14.45.
as a yellow oil. IR (microlayer): ν = 3065, 3034, 2962, 2935, 2874,
˜
2216, 1612, 1576, 1493, 1463, 1448, 1324, 1283, 1250, 1184, 1121,
1087, 1057, 1027, 988, 922, 760, 698, 662, 525 cm–1 1H NMR
.
(400.13 MHz, CDCl3): δ = 7.50–7.40 (m, 5 H, Ph), 6.92 (s, 1 H, 4-
3
H), 6.85 (s, 1 H, 5-H), 5.57 (t, JH6,CH = 6.4 Hz, 1 H, 6-H), 4.93
2
(s, 1 H, 9-H), 3.77 (s, 3 H, N-CH3), 2.10 (m, 2 H, C6-CH2-), 1.40–
1.26 (m, 2 H, C6-CH2-CH2-), 0.88 [t, JH,H = 7.1 Hz, 3 H, C6-
(Z)-3-{[(1-Ethyl-1H-imidazol-2-yl)pentyl]oxy}-3-phenyl-2-propene-
nitrile (4i): Analogously, from acetylene 2b (0.127 g, 1 mmol), n-
pentanal (3c; 0.086 g, 1 mmol), and 1-ethylimidazole (1b; 0.096 g,
1 mmol) (20–25 °C, 24 h) enol ether 4i (0.166 g, 54%) was obtained
3
(CH2)2-CH3] ppm. 13C NMR (100.62 MHz, CDCl3): δ = 171.5 (C-
8), 144.7 (C-2), 134.0 (Ci, Ph), 131.4 (Cp, Ph), 129.1 (Cm, Ph), 127.8
(C-4), 127.3 (Co, Ph), 122.8 (C-5), 116.8 (C-10, CN), 78.0 (C-9),
77.1 (C-6), 36.0 (C6-CH2-), 33.8 (N-CH3), 18.7 (C6-CH2-CH2-),
13.8 [C6-(CH2)2-CH3] ppm. 15N NMR (40.55 MHz, CDCl3): δ =
–120.0 (N-3), –125.1 (CN-10), –222.9 (N-1) ppm. C17H19N3O
(281.36): calcd. C 72.57, H 6.81, N 14.91; found C 72.05, H 6.80,
N 14.45.
as a light-brown oil. IR (microlayer): ν = 3065, 2958, 2933, 2872,
˜
2216, 1608, 1576, 1492, 1466, 1448, 1379, 1331, 1277, 1258, 1180,
1
1158, 1090, 1028, 992, 919, 896, 849, 761, 697, 662, 526 cm–1. H
NMR (400.13 MHz, CDCl3): δ = 7.50–7.40 (m, 5 H, Ph), 6.98 (s,
3
1 H, 4-H), 6.93 (s, 1 H, 5-H), 5.68 (t, JH6,CH = 6.4 Hz, 1 H, 6-
2
H), 4.94 (s, 1 H, 9-H), 4.15 (q, 3JH,H = 7.1 Hz, 2 H, N-CH2-), 2.25–
2.14 (m, 2 H, C6-CH2-), 1.39 (t, 3 H, N-CH2-CH3), 1.33–1.17 [m,
4 H, C6-CH2-(CH2)2-], 0.83 [t, JH,H = 7.1 Hz, 3 H, C6-(CH2)3-
(Z)-3-{[(1-Methyl-1H-imidazol-2-yl)pentyl]oxy}-3-phenyl-2-propene-
nitrile (4f): Analogously, from acetylene 2b (0.127 g, 1 mmol), n-
pentanal (3c; 0.086 g, 1 mmol), and 1-methylimidazole (1a; 0.082 g,
1 mmol) (20–25 °C, 24 h) enol ether 4f (0.091 g, 31%) was obtained
3
CH3] ppm. 13C NMR (100.62 MHz, CDCl3): δ = 170.6 (C-8), 143.6
(C-2), 132.58 (Ci, Ph), 130.9 (Cp, Ph), 128.4 (Cm, Ph), 127.7 (C-4),
126.7 (Co, Ph), 119.7 (C-5), 116.2 (C-10, CN), 76.8 (C-9), 76.3 (C-
6), 40.7 (N-CH2-), 33.2 (C6-CH2-), 26.8 (C6-CH2-CH2-), 21.9 [C6-
(CH2)2-CH2-], 16.1 (N-CH2-CH3), 13.4 [C6-(CH2)3-CH3] ppm.
C19H23N3O (309.41): calcd. C 73.76, H 7.49, N 13.58; found C
73.25, H 7.28, N 13.23.
as a yellow oil. IR (microlayer): ν = 3064, 2958, 2932, 2872, 2216,
˜
1612, 1576, 1493, 1466, 1448, 1413, 1330, 1282, 1248, 1183, 1088,
1028, 992, 919, 760, 699, 661, 525 cm–1. 1H NMR (400.13 MHz,
CDCl3): δ = 7.50–7.40 (m, 5 H, Ph), 6.83 (s, 1 H, 4-H), 6.76 (s, 1
3
H, 5-H), 5.58 (t, JH6,CH = 6.4 Hz, 1 H, 6-H), 4.91 (s, 1 H, 9-H),
2
(Z)-3-[(1-Isobutyl-1H-imidazol-2-yl)ethoxy]-3-phenyl-2-propeneni-
trile (4j): Analogously, from acetylene 2b (0.127 g, 1 mmol), ethanal
(3a; 0.132 g, 3 mmol), and 1-isobutylimidazole (1c; 0.124 g,
1 mmol) (20–25 °C, 24 h) enol ether 4j (0.182 g, 62%) was obtained
3.79 (s, 3 H, N-CH3), 2.25–2.12 (m, 2 H, C6-CH2-), 1.36–1.18 [m,
4 H, C6-CH2-(CH2)2-], 0.83 [t, JH,H = 7.1 Hz, 3 H, C6-(CH2)3-
3
CH3] ppm. 13C NMR (100.62 MHz, CDCl3): δ = 171.2 (C-8), 144.5
(C-2), 132.9 (Ci, Ph), 131.3 (Cp, Ph), 128.9 (Cm, Ph), 127.7 (C-4),
127.2 (Co, Ph), 122.7 (C-5), 116.7 (C-10, CN), 77.8 (C-9), 77.0 (C-
6), 33.5 (N-CH3), 33.5 (C6-CH2-), 27.2 (C6-CH2-CH2-), 22.3 [C6-
(CH2)2-CH2-], 13.8 [C6-(CH2)3-CH3] ppm. C18H20N3O (295.38):
calcd. C 73.19, H 7.17, N 14.23; found C 73.17, H 7.08, N 14.13.
as a light-brown oil. IR (microlayer): ν = 3066, 2964, 2936, 2874,
˜
2215, 1650, 1606, 1575, 1491, 1469, 1448, 1376, 1344, 1306, 1277,
1254, 1183, 1151, 1109, 1090, 1062, 1014, 978, 921, 896, 841, 762,
733, 697, 666, 533 cm–1. 1H NMR (400.13 MHz, CDCl3): δ = 7.50–
7.30 (m, 5 H, Ph), 7.00 (s, 1 H, 4-H), 6.89 (s, 1 H, 5-H), 6.02 (q,
(Z)-3-[(1-Ethyl-1H-imidazol-2-yl)ethoxy]-3-phenyl-2-propenenitrile
(4g): Analogously, from acetylene 2b (0.127 g, 1 mmol), ethanal
(3a; 0.132 g, 3 mmol), and 1-ethylimidazole (1b; 0.096 g, 1 mmol)
(20–25 °C, 24 h) enol ether 4g (0.132 g, 49%) was obtained as a
3JH6,CH = 6.4 Hz, 1 H, 6-H), 5.09 (s, 1 H, 9-H), 3.81–3.79 (m, 2
3
3
H, N-CH2-), 2.03–1.96 (m, 1 H, N-CH2-CH-), 1.81 (d, JH,H
=
3
6.8 Hz, 3 H, C6-CH3), 0.88 [d, JH,H = 6.8 Hz, 6 H, N-CH2-CH-
(CH3)2] ppm. 13C NMR (100.62 MHz, CDCl3): δ = 169.1 (C-8),
144.6 (C-2), 132.9 (Ci, Ph), 130.9 (Cp, Ph), 128.3 (Cm, Ph), 127.4
(C-4), 126.4 (Co, Ph), 120.8 (C-5), 116.4 (C-10, CN), 75.5 (C-9),
70.9 (C-6), 52.9 (N-CH2-), 29.6 (N-CH2-CH-), 19.4 (C6-CH3), 18.4
[N-CH2-CH-(CH3)2] ppm. C18H21N3O (295.38): calcd. C 73.19, H
7.17, N 14.23; found C 73.72, H 7.15, N 14.30.
light-brown oil. IR (microlayer): ν = 3066, 2984, 2938, 2214, 1651,
˜
1606, 1569, 1492, 1465, 1448, 1378, 1347, 1305, 1286, 1257, 1183,
1150, 1114, 1088, 1059, 1025, 963, 920, 896, 850, 760, 697, 666,
1
521 cm–1. H NMR (400.13 MHz, CDCl3): δ = 7.60–7.40 (m, 5 H,
3
Ph), 6.97 (s, 1 H, 4-H), 6.92 (s, 1 H, 5-H), 5.92 (q, JH6,CH
=
6.4 Hz, 1 H, 6-H), 5.03 (s, 1 H, 9-H), 4.14 (q, 3JH,H = 7.1 Hz, 22H,
N-CH2-), 1.76 (s, 3 H, C6-CH3), 1.38 (t, 3 H, N-CH2-CH3) ppm.
13C NMR (100.62 MHz, CDCl3): δ = 169.8 (C-8), 144.4 (C-2),
132.8 (Ci, Ph), 131.1 (Cp, Ph), 128.5 (Cm, Ph), 127.6 (C-4), 126.6
(Co, Ph), 120.1 (C-5), 116.4 (C-10, CN), 76.6 (C-9), 72.1 (C-6), 40.8
(N-CH2-), 18.7 (C6-CH3), 16.1 (N-CH2-CH3) ppm. C16H17N3O
(267.33): calcd. C 71.89, H 6.41, N 15.72; found C 71.40, H 6.31,
N 15.74.
(Z)-3-[(1-Isobutyl-1H-imidazol-2-yl)butoxy]-3-phenyl-2-propeneni-
trile (4k): Analogously, from acetylene 2b (0.127 g, 1 mmol), n-but-
anal (3b; 0.072 g, 1 mmol), and 1-isobutylimidazole (1c; 0.124 g,
1 mmol) (20–25 °C, 24 h) enol ether 4k (0.189 g, 59 %) was ob-
tained as a brown oil. IR (microlayer): ν = 3065, 2963, 2934, 2874,
˜
2216, 1605, 1575, 1491, 1468, 1448, 1370, 1344, 1323, 1279, 1254,
1180, 1154, 1095, 1027, 982, 950, 932, 894, 756, 697, 663, 526 cm–1.
1H NMR (400.13 MHz, CDCl3): δ = 7.45–7.32 (m, 5 H, Ph), 7.01
3
(Z)-3-[(1-Ethyl-1H-imidazol-2-yl)butoxy]-3-phenyl-2-propenenitrile (s, 1 H, 4-H), 6.89 (s, 1 H, 5-H), 5.81 (t, JH6,CH = 6.4 Hz, 1 H, 6-
2
(4h): Analogously, from acetylene 2b (0.127 g, 1 mmol), n-butanal
(3b; 0.072 g, 1 mmol), and 1-ethylimidazole (1b; 0.096 g, 1 mmol)
(20–25 °C, 24 h) enol ether 4h (0.160 g, 54%) was obtained as a
H), 5.01 (s, 1 H, 9-H), 3.83–3.80 (m, 2 H, N-CH2-), 2.24–2.15 (m,
2 H, C6-CH2-), 2.04–1.97 (m, 1 H, N-CH2-CH-), 1.44–1.26 (m, 2
H, C6-CH2-CH2-), 0.92–0.87 [m, 9 H, N-CH2-CH-(CH3)2 and C6-
yellow oil. IR (microlayer): ν = 3064, 2963, 2930, 2874, 2855, 2218, (CH2)2-CH3] ppm. 13C NMR (100.62 MHz, CDCl3): δ = 170.5 (C-
˜
1612, 1575, 1492, 1448, 1406, 1379, 1280, 1260, 1178, 1160, 1101,
8), 144.4 (C-2), 133.2 (Ci, Ph), 131.3 (Cp, Ph), 128.8 (Cm, Ph), 128.0
(C-4), 127.1 (Co, Ph), 121.1 (C-5), 116.9 (C-10, CN), 76.1 (C-9),
1
1027, 965, 918, 760, 695 cm–1. H NMR (400.13 MHz, CDCl3): δ
= 7.50–7.40 (m, 5 H, Ph), 6.98 (s, 1 H, 4-H), 6.93 (s, 1 H, 5-H), 75.5 (C-6), 53.4 (N-CH2-), 35.6 (C6-CH2-), 30.1 (N-CH2-CH-), 19.8
3
5.67 (t, JH6,CH = 6.4 Hz, 1 H, 6-H), 4.93 (s, 1 H, 9-H), 4.20 (q, [N-CH2-CH-(CH3)2], 18.4 (C6-CH2-CH2-), 13.8 [C6-(CH2)2-CH3]
3JH,H = 6.8 Hz,22 H, N-CH2-), 2.25–2.12 (m, 2 H, C6-CH2-), 1.43– ppm. C20H25N3O (323.44): calcd. C 74.27, H 7.79, N 12.99; found
1.25 (m, 2 H, C6-CH2-CH2-), 1.36 (t, 3 H, N-CH2-CH3), 0.88 [t, C 74.42, H 7.56, N 12.86.
1776
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 1772–1777

Novel Three-Component Reaction
(Z)-3-{[(1-Isobutyl-1H-imidazol-2-yl)pentyl]oxy}-3-phenyl-2-pro-
penenitrile (4l): Analogously, from acetylene 2b (0.127 g, 1 mmol),
n-pentanal (3c; 0.086 g, 1 mmol), and 1-isobutylimidazole (1c;
0.124 g, 1 mmol) (20–25 °C, 48 h) enol ether 4l (0.193 g, 57%) was
Acknowledgments
This work was supported by the Russian Fund for Basic Research
(Grant No. 08–03–00156), Presidium of RAS (Program 15), and
Presidium of Department of Chemical Sciences and Materials RAS
(Grant No. 5.1).
obtained as a light-brown oil. IR (microlayer): ν = 3066, 2960,
˜
2932, 2873, 2216, 1605, 1575, 1520, 1492, 1468, 1448, 1391, 1370,
1331, 1312, 1276, 1254, 1180, 1155, 1096, 1044, 1029, 1001, 981,
1
963, 920, 896, 850, 818, 756, 697, 662, 554, 526, 506, 439 cm–1. H
NMR (400.13 MHz, CDCl3): δ = 7.40–7.30 (m, 5 H, Ph), 7.02 (s,
3
[1]
a) M. R. Grimmett in Comprehensive Heterocyclic Chemistry II
(Eds.: A. R. Katrizky, C. W. Rees, E. F. V. Scriven), Pergamon,
Oxford, 1996, vol. 3, pp. 77–220; b) C. A. Zificsak, D. J. Hlasta,
Tetrahedron 2004, 60, 8991–9016; c) A. Puratchikody, M. Do-
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Cauteruccio, R. Rossi, Tetrahedron 2007, 63, 4571–4624; e) S.
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a) B. Iddon, Heterocycles 1985, 23, 417–443; b) B. Iddon, R. I.
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S. K. Sharma, M. Tandon, J. W. Lown, J. Org. Chem. 2000, 65,
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a) D. J. Hlasta, Org. Lett. 2001, 3, 157–159; b) Y. Deng, D. J.
Hlasta, Org. Lett. 2002, 4, 4017–4020; c) Y. Deng, D. J. Hlasta,
Tetrahedron Lett. 2002, 43, 189–192; d) C. Zificsak, D. J. Hla-
sta, Tetrahedron Lett. 2005, 46, 4789–4792.
a) S. Pivsa-Art, T. Satoh, Y. Kawamura, M. Miura, M. No-
mura, Bull. Chem. Soc. Jpn. 1998, 71, 467–473; b) M. Ababri,
F. Dehmel, P. Knochel, Tetrahedron Lett. 1999, 40, 7449–7453;
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2007, 63, 1970–1980.
1 H, 4-H), 6.89 (s, 1 H, 5-H), 5.82 (t, JH6,CH = 6.4 Hz, 1 H, 6-
H), 5.00 (s, 1 H, 9-H), 3.86–3.83 (m, 2 H, N-C2H2-), 2.25–2.05 (m,
2 H, C6-CH2-), 2.04–1.99 (m, 1 H, N-CH2-CH-), 1.32–1.26 [m, 4
3
H, C6-CH2-(CH2)2-], 0.93 [d, JH,H = 6.8 Hz, 6 H, N-CH2-CH-
(CH3)2], 0.86–0.83 [m, 3 H, C6-(CH2)3-CH3] ppm. 13C NMR
(100.62 MHz, CDCl3): δ = 170.2 (C-8), 144.3 (C-2), 133.1 (Ci, Ph),
131.1 (Cp, Ph), 128.5 (Cm, Ph), 127.8 (C-4), 126.8 (Co, Ph), 120.8
(C-5), 116.6 (C-10, CN), 75.6 (C-9), 75.5 (C-6), 53.2 (N-CH2-), 33.1
(C6-CH2-), 29.9 (N-CH2-CH-), 26.9 (C6-CH2-CH2-), 22.2 [C6-
(CH2)2-CH2-], 19.60 [N-CH2-CH-(CH3)2], 13.6 [C6-(CH2)3-CH3]
ppm. C21H27N3O (337.46): calcd. C 74.74, H 8.06, N 12.45; found
C 74.32, H 7.86, N 12.36.
[2]
[3]
(Z)-3-[1-(1-Benzyl-1H-imidazol-2-yl)ethoxy]-3-phenyl-2-propene-
nitrile (4m): Analogously, from acetylene 2b (0.127 g, 1 mmol),
ethanal (3a; 0.132 g, 3 mmol), and 1-benzylimidazole (1d; 0.158 g,
1 mmol) in CH3CN (1 mL) (20–25 °C, 4 d) enol ether 4m (0.135 g,
[4]
[5]
41%) was obtained as a brown oil. IR (microlayer): ν = 3066, 3033,
˜
2986, 2937, 2874, 2214, 1648, 1607, 1574, 1494, 1449, 1434, 1377,
1345, 1321, 1303, 1283, 1222, 1166, 1114, 1078, 1063, 1028, 1003,
[6]
967, 919, 897, 846, 759, 697, 664, 579, 459 cm–1 1H NMR
.
(400.13 MHz, CDCl3): δ = 7.27–7.07 (m, 10 H, 2 Ph), 7.03 (s, 1 H,
4-H), 6.88 (s, 1 H, 5-H), 5.89 (q, 3JH6,CH = 6.5 Hz, 1 H, 6-H), 5.38
3
2
(d, JH,H = 16.0 Hz, 1 H, CH2Ph), 5.25 (d, 1 H, CH2Ph), 4.97 (s,
1 H, 9-H), 1.68 (d, 3 H, C6-CH3) ppm. 13C NMR (100.62 MHz,
CDCl3): δ = 169.9 (C-8), 145.3 (C-2), 136.3 (Ci, Ph in Bn), 133.1
(Ci, Ph), 131.3 (C-4), 128.8 (Cm, Ph in Bn and Ph), 128.0 (Cp, Ph
in Bn), 127.9 (Cp, Ph), 126.9 (Co, Ph in Bn and Ph), 122.0 (C-
5), 116.7 (C-10, CN), 76.7 (C-9), 72.4 (C-6), 49.9 (N-CH2-) ppm.
C21H19N3O (329.40): calcd. C 76.57, H 5.81, N 12.76; found C
76.22, H 5.65, N 12.30.
[7] Y. Fukumoto, K. Sawada, M. Hagihara, N. Chatani, S. Murai,
Angew. Chem. Int. Ed. 2002, 41, 2779–2781.
[8] a) V. Nair, S. Bindu, V. Sreekumar, N. P. Rath, Org. Lett. 2003,
5, 665–667; b) V. Nair, C. Rajesh, A. U. Vinod, S. Bindu, A. R.
Sreekanth, J. S. Mathen, L. Balagopal, Acc. Chem. Res. 2003,
36, 899–907; c) V. Nair, S. Bindu, V. Sreekumar, Angew. Chem.
Int. Ed. 2004, 43, 5130–5135; d) V. Nair, R. S. Menon, V. Sreek-
umar, Pure Appl. Chem. 2005, 77, 1191–1198; e) V. Nair, V.
Sreekumar, S. Bindu, E. Suresh, Org. Lett. 2005, 7, 2297–2300.
[9] a) B. A. Trofimov, L. V. Andriyankova, K. V. Belyaeva, A. G.
MalЈkina, L. P. Nikitina, A. V. Afonin, I. A. Ushakov, J. Org.
Chem. 2008, 73, 9155–9157; b) B. A. Trofimov, L. V. Andriyan-
kova, K. V. Belyaeva, A. G. MalЈkina, L. P. Nikitina, Izv. Akad.
Nauk Ser. Khim. 2008, 2191–2192; c) B. A. Trofimov, L. V. An-
driyankova, K. V. Belyaeva, A. G. MalЈkina, L. P. Nikitina,
A. V. Afonin, I. A. Ushakov, Mendeleev Commun. 2009, 19, 42–
44.
[10] Yu. M. Skvortsov, A. G. MalЈkina, A. N. Volkov, B. A. Trofi-
mov, E. B. Oleinikova, I. V. Kazin, V. V. Gedymin, Izv. Akad.
Nauk SSSR, Ser. Khim. 1978, 872–875.
[11] B. A. Trofimov, Heteroatomic Derivatives of Acetylene: New
Polyfunctional Monomers, Reagents, and Intermediates, Nauka,
Moscow, 1981, 320 p. (in Russian).
(Z)-3-[1-(1-Vinyl-1H-imidazol-2-yl)ethoxy]-3-phenyl-2-propeneni-
trile (4n): Analogously, from acetylene 2b (0.127 g, 1 mmol),
ethanal (3a; 0.132 g, 3 mmol), and 1-vinylimidazole (1d; 0.094 g,
1 mmol) (20–25 °C, 13 d) enol ether 4n (0.163 g, 62%) was obtained
as a yellow oil. IR (microlayer): ν = 3067, 3036, 2987, 2936, 2872,
˜
2214, 1646, 1608, 1569, 1524, 1491, 1448, 1429, 1380, 1345, 1321,
1303, 1277, 1257, 1177, 1168, 1113, 1082, 1065, 1048, 1027, 1003,
962, 894, 854, 762, 695, 670, 567 cm–1. 1H NMR (400.13 MHz,
CDCl3): δ = 7.50–7.30 (m, 5 H, Ph and 1 H, HX), 7.22 (s, 1 H, 4-
3
H), 6.96 (s, 1 H, 5-H), 5.82 (q, JH6,CH = 6.6 Hz, 1 H, 6-H), 5.27
(d, 3JHB,HX = 15.3 Hz, 1 H, HB), 5.02 (s,31 H, 9-H), 4.96 (d, 3JHA,HX
= 8.1 Hz, 1 H, HA), 1.74 (d, 3 H, C6-CH3) ppm. 13C NMR
(100.62 MHz, CDCl3): δ = 170.3 (C-8), 144.8 (C-2), 132.8 (Ci, Ph),
131.5 (C-HX), 129.2 (Cp, Ph), 129.0 (Cm, Ph), 128.7 (C-4), 127.1
(Co, Ph), 117.7 (C-5), 116.6 (C-10, CN), 104.0 (HA-C-HB), 78.4 (C-
9), 72.9 (C-6), 19.5 (C6-CH3) ppm. C16H15N3O (265.31): calcd. C
72.43, H 5.70, N 15.84; found C 72.00, H 5.49, N 15.50.
[12] O. V. Starikova, G. V. Dolgushin, L. I. Larina, T. N. Komarova,
V. A. Lopyrev, Arkivoc 2003, 13, 119–124.
Received: December 2, 2009
Published Online: February 12, 2010
Eur. J. Org. Chem. 2010, 1772–1777
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