Synthesis of (Z)-2-[quinazolin-4(3H)-ylidene]acetonitriles by the reaction of N-(2-cyanophenyl)alkanimidates with 2-lithioacetonitrile

Article abstract of DOI:10.1055/s-2008-1067235

An efficient preparation of (Z)-2-[quinazolin-4(3H)-ylidene]acetonitriles has been achieved in one pot by addition of 2-lithioacetonitrile to the cyano carbon of N-(2-cyanophenyl)alkanimidates, followed by intramolecular attack of the resulting imino anio

Full text of DOI:10.1055/s-2008-1067235

2874
PAPER
Synthesis of (Z)-2-[Quinazolin-4(3H)-ylidene]acetonitriles by the Reaction of
N-(2-Cyanophenyl)alkanimidates with 2-Lithioacetonitrile
Synthesis of
(
Z
)
-2-
a
[Quinazolin
z
-4(3
H
)-yli
u
dene]acetoni
h
trile
s
iro Kobayashi,* Takahiro Ukon, Hidenari Nakano, Shuhei Fukamachi, Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101
Koyama-minami, Tottori 680-8552, Japan
Fax +81(857)315263; E-mail: kkoba@chem.tottori-u.ac.jp
Received 16 April 2008; revised 22 May 2008
R1
R2
N
R3
R1
R2
N
R3
OR4
Abstract: An efficient preparation of (Z)-2-[quinazolin-4(3H)-
ylidene]acetonitriles has been achieved in one pot by addition of 2-
lithioacetonitrile to the cyano carbon of N-(2-cyanophenyl)alkan-
imidates, followed by intramolecular attack of the resulting imino
anion on the imidate carbon with loss of alkoxide and subsequent
tautomerization.
LiCH2CN
NH
CN
THF, –78 °C
CN
1
2
Scheme 1
Key words: carbanions, fused-ring system, heterocycles, nitriles,
ring closure, quinazoline
ally good to excellent (Table 1, entries 1–9). Unfortunate-
ly, however, the addition–ring closure reactions using N-
(2-cyano-4,5-dimethoxyphenyl)alkanimidates 1j–l gave
somewhat disappointing results and lower yields of the
corresponding products 2j–l (Table 1, entries 10–12)
were obtained and substantial amounts of starting materi-
als were recovered. The use of a greater excess of 2-lithio-
acetonitrile and prolonged reaction times did not improve
the yields. These results may be attributed to the lower re-
activity of the cyano groups of 1j–l due to the electron-do-
nating properties of the methoxy groups on the benzene
ring.
We previously reported that sequential addition–ring clo-
sure reactions between 2-(2-methoxyvinyl)benzonitriles
with 2-lithioacetonitrile took place successfully to afford
1-aminonaphthalene-2-carbonitriles in good yields.1 We
were interested in investigating reactions of N-(cyanophe-
nyl)alkanimidates with 2-lithioacetonitrile, which would
be expected to give 4-aminoquinoline-3-carbonitriles.
However, we found that the reactions led to the formation
of (Z)-2-[quinazolin-4(3H)-ylidene]acetonitriles. In this
report we wish to report on the details of the synthesis of
this class of quinazoline derivatives. A number of effi-
cient syntheses of quinazoline derivatives have recently
been reported,2 because some of them exhibit biological
activities3 and a number of molecules having the quinazo-
line skeleton exist in nature.4 However, only a few meth-
ods for the preparation of 2-[quinazolin-4(3H)-
ylidene]acetic acid derivatives have been recorded.5
These methods involve multistep sequences and are of
limited generality.
Table 1 Preparation of (Z)-2-(Quinazolin-4(3H)-ylidene)aceto-
nitrile Derivatives 2
Entry Substrate
R1
Time Product Isolated
R2
H
R3 R4 (h)
yield (%)
84
1
1a
1b
1c
H
H
H
Me Me
3
3
3
2
2
2
1
1
1
5
5
5
2a
2b
2c
2d
2e
2f
2
H
Et
Pr
Et
77
The sequential addition–ring closure reactions between
N-(2-cyanophenyl)alkanimidates 1 and 2-lithioacetoni-
trile, which can be easily generated as described previous-
ly,1,6 were carried out as illustrated in Scheme 1. The
starting imidates 1 were prepared by the reaction of com-
mercially available 2-aminobenzonitriles and the appro-
priate orthoalkanoates in the presence of trifluoroacetic
acid.7 The imidates thus obtained were allowed to react
with two equivalents of 2-lithioacetonitrile in tetrahydro-
furan at –78 °C for the reaction times given in Table 1.
The corresponding products, (Z)-2-[quinazolin-4(3H)-
ylidene]acetonitriles 2, were isolated by preparative TLC
on silica gel after the usual workup. The reactions were
generally clean and the yields of the products 2 are gener-
3
H
Me
86
4
1d Cl
H
Me Me
88
5
1e
1f
1g
1h
1i
Cl
Cl
H
H
Et
Pr
Et
87
6
H
Me
85
7
Cl
Cl
Cl
Me Me
2g
2h
2i
94
8
H
Et
Pr
Et
90
9
H
Me
83
10
11
12
1j
OMe OMe Me Me
2j
37
1k OMe OMe Et
1l OMe OMe Pr
Et
2k
2l
41
Me
41
SYNTHESIS 2008, No. 18, pp 2874–2878
x
x.
x
x
.
2
0
0
8
Advanced online publication: 22.08.2008
DOI: 10.1055/s-2008-1067235; Art ID: F09008SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of (Z)-2-[Quinazolin-4(3H)-ylidene]acetonitriles
2875
JMS AX505 HA spectrometer (EI, 70 eV). TLC was carried out on
a Merck Kieselgel 60 PF254. All of the organic solvents used in this
study were dried over appropriate drying agents and distilled prior
to use. All chemicals used in this study were commercially avail-
able.
R3
R1
R2
N
N
LiCH2CN
OR4
1
N
CN
3
N-(2-Cyanophenyl)alkanimidates 1
These compounds were prepared by 2-aminobenzonitriles with ap-
propriate orthoalkanoates in the presence of TFA under conditions
described by Hosmane et al. for the preparation of methyl N-(2-cy-
anophenyl)formimidate.7
R1
R2
R3
N
–
–OR4
CN
Methyl N-(2-Cyanophenyl)acetimidate (1a)8
4
Colorless liquid; yield: 95%; bp 72–74 °C (bath temp)/0.93 mbar.
IR (neat): 2226, 1670 cm–1.
1H NMR (500 MHz): d = 1.88 (s, 3 H), 3.86 (s, 3 H), 6.86 (d, J = 8.2
Hz, 1 H), 7.10 (td, J = 7.8, 0.9 Hz, 1 H), 7.49 (ddd, J = 8.2, 7.8, 1.4
Hz, 1 H), 7.58 (dd, J = 7.8, 1.4 Hz, 1 H).
R1
R2
N
R3
LiCH2CN
H3O+
2
N
CN
5
Anal. Calcd for C10H10N2O: C, 68.95; H, 5.79; N, 16.08. Found: C,
68.77; H, 5.93; N, 16.05.
Scheme 2
Ethyl N-(2-Cyanophenyl)propanimidate (1b)
Colorless liquid; yield: 99%; bp 110 °C (bath temp)/0.75 mbar.
IR (neat): 2224, 1661 cm–1.
1H NMR (500 MHz): d = 1.11 (t, J = 7.3 Hz, 3 H), 1.37 (t, J = 7.3
Hz, 3 H), 2.16 (q, J = 7.3 Hz, 2 H), 4.39 (q, J = 7.3 Hz, 2 H), 6.83
(d, J = 8.2 Hz, 1 H), 7.07 (dd, J = 7.8, 7.3 Hz, 1 H), 7.47 (ddd,
J = 7.8, 7.3, 1.4 Hz, 1 H), 7.57 (dd, J = 7.8, 1.4 Hz, 1 H).
The stereochemistry of the products 2 was unambiguously
assigned to be Z on the basis of NOE experiments. For ex-
ample, irradiation of the signal at d = 4.59, assigned to the
vinyl proton a to the cyano group of 2a, resulted in an en-
hancement (11%) of the signal at d = 7.67, assigned to H5
of the quinazoline ring.
Anal. Calcd for C14H14N2O: C, 71.26; H, 6.98; N, 13.85. Found: C,
71.19; H, 7.13; N, 13.74.
It was necessary to use two equivalents of 2-lithioacetoni-
trile to complete the reactions. For example, the reaction
of 1a with an equimolar amount of 2-lithioacetonitrile
gave diminished yields (38%) of the desired product 2a
and a substantial quantity of the starting material was re-
covered (46%). The necessity of two equivalents of 2-
lithioacetonitrile may be explainable as follows
(Scheme 2). 2-Lithioacetonitrile first adds to the cyano
carbon of 1 to generate the imino anion intermediate 3.
This anion attacks intramolecularly on the imidate carbon
to form the quinazoline intermediate 4 with loss of alkox-
ide. The hydrogen a to the cyano group is removed by the
second equivalent of 2-lithioacetonitrile to give the enam-
ino anion intermediate 5, which is finally quenched by
aqueous workup to afford 2.
Methyl N-(2-Cyanophenyl)butanimidate (1c)8
Pale-yellow liquid; yield: 84%; bp 140 °C (bath temp)/0.8 mbar.
IR (neat): 2224, 1666 cm–1.
1H NMR (500 MHz): d = 0.86 (t, J = 7.3 Hz, 3 H), 1.58 (sext,
J = 7.3 Hz, 2 H), 2.15 (t, J = 7.3 Hz, 2 H), 3.86 (s, 3 H), 6.84 (d,
J = 8.2 Hz, 1 H), 7.09 (ddd, J = 8.2, 7.8, 1.4 Hz, 1 H), 7.48 (td,
J = 7.8, 1.4 Hz, 1 H), 7.58 (dd, J = 7.8, 1.4 Hz, 1 H).
Anal. Calcd for C14H14N2O: C, 71.26; H, 6.98; N, 13.85. Found: C,
71.36; H, 6.98; N, 13.77.
Methyl N-(5-Chloro-2-cyanophenyl)acetimidate (1d)
Pale-yellow solid; yield: 76%; mp 61–62 °C (hexane–Et2O).
IR (KBr): 2224, 1678 cm–1.
1H NMR (500 MHz): d = 1.91 (s, 3 H), 3.85 (s, 3 H), 6.89 (d, J = 1.8
Hz, 1 H), 7.09 (dd, J = 8.2, 1.8 Hz, 1 H), 7.50 (d, J = 8.2 Hz, 1 H).
13C NMR: d = 16.58, 54.16, 103.73, 116.64, 122.16, 123.54,
133.76, 139.65, 153.42, 163.75.
In conclusion, we have shown that the reaction of N-(cy-
anophenyl)alkanimidates with 2-lithioacetonitrile pro-
vides a new and versatile method for the general
preparation of (Z)-2-[quinazolin-4(3H)-ylidene]acetoni-
triles. The present method may be of value in organic syn-
thesis because of its ease of operation as well as the
readily availability of the starting materials.
Anal. Calcd for C10H9ClN2O: C, 57.57; H, 4.35; N, 13.43. Found:
C, 57.50; H, 4.48; N, 13.29.
Ethyl N-(5-Chloro-2-cyanophenyl)propanimidate (1e)
Colorless liquid; yield: 93%; bp 115 °C (bath temp)/1.2 mbar.
IR (neat): 2228, 1661 cm–1.
1H NMR (500 MHz): d = 1.13 (t, J = 7.8 Hz, 3 H), 1.37 (t, J = 7.3
Hz, 3 H), 2.18 (q, J = 7.8 Hz, 2 H), 4.28 (q, J = 7.3 Hz, 2 H), 6.86
(d, J = 2.3 Hz, 1 H), 7.06 (dd, J = 8.2, 2.3 Hz, 1 H), 7.49 (d, J = 8.2
Hz, 1 H).
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were de-
termined with a Shimadzu FTIR-8300 spectrophotometer. The H
NMR spectra were determined in CDCl3 using TMS as an internal
reference with a Jeol ECP500 FT NMR spectrometer operating at
500 MHz or a Jeol LA400 FT NMR spectrometer operating at 400
MHz. The 13C NMR spectra were determined in CDCl3 using TMS
as an internal reference with a Jeol ECP500 FT NMR spectrometer
operating at 125 MHz. LR-MS spectra were measured by a Jeol
1
Anal. Calcd for C12H13ClN2O: C, 60.89; H, 5.54; N, 11.84. Found:
C, 60.74; H, 5.63; N, 11.91.
Synthesis 2008, No. 18, 2874–2878 © Thieme Stuttgart · New York

2876
K. Kobayashi et al.
PAPER
Methyl N-(4,5-Dimethoxy-2-cyanophenyl)butanimidate (1l)
Methyl N-(5-Chloro-2-cyanophenyl)butanimidate (1f)
Colorless liquid; yield: 89%; bp 120 °C (bath temp)/0.64 mbar.
Colorless liquid; yield: 98%; bp 165 °C (bath temp)/0.75 mbar.
IR (neat): 2226, 1666 cm–1.
IR (neat): 2216, 1668, 1607 cm–1.
1H NMR (500 MHz,): d = 0.88 (t, J = 7.3 Hz, 3 H), 1.60 (sext,
J = 7.3 Hz, 2 H), 2.17 (t, J = 7.3 Hz, 2 H), 3.85 (s, 3 H), 6.86 (d,
J = 1.8 Hz, 1 H), 7.07 (dd, J = 8.2, 1.8 Hz, 1 H), 7.50 (d, J = 8.2 Hz,
1 H).
1H NMR (500 MHz): d = 0.88 (t, J = 7.3 Hz, 3 H), 1.60 (sext,
J = 7.3 Hz, 2 H), 2.17 (t, J = 7.3 Hz, 2 H), 3.84 (s, 3 H), 3.87 (s, 3
H), 3.89 (s, 3 H), 6.33 (s, 1 H), 6.96 (s, 1 H).
Anal. Calcd for C14H18N2O3: C, 64.10; H, 6.92; N, 10.68. Found: C,
64.03; H, 6.902; N, 10.80.
Anal. Calcd for C12H13ClN2O: C, 60.89; H, 5.54; N, 11.84. Found:
C, 60.62; H, 5.70; N, 11.72.
(Z)-2-[2-Methylquinazolin-4(3H)-ylidene]acetonitrile (2a);
Typical Procedure
Methyl N-(4-Chloro-2-cyanophenyl)acetimidate (1g)
White solid; yield: 83%; bp 105 °C (bath temp)/0.63 mbar; mp 72–
73 °C.
IR (KBr): 2230, 1676 cm–1.
1H NMR (500 MHz): d = 1.89 (s, 3 H), 3.85 (s, 3 H), 6.81 (d, J = 8.7
Hz, 1 H), 7.45 (dd, J = 8.7, 2.3 Hz, 1 H), 7.55 (d, J = 2.3 Hz, 1 H).
To a stirred soln of MeCN (82 mg, 2.0 mmol) in THF (6 mL) at –78
°C was added dropwise 1.5 M BuLi in n-hexane (1.3 mL, 2.0
mmol). After 15 min, the imidate 1a (0.17 g, 1.0 mmol) was added,
and stirring was continued for an additional 3 h at the same temper-
ature. Aq sat. NH4Cl (15 mL) was added and organic materials were
extracted with Et2O (3 × 10 mL). The combined extracts were
washed with brine (10 mL), dried (anhyd Na2SO4), and evaporated.
The residue was purified by preparative TLC (silica gel, 1:10
EtOAc–benzene) to give 2a as a pale-yellow solid; yield: 0.15 g
(84%); mp 114–115 °C (hexane–CH2Cl2).
Anal. Calcd for C10H9ClN2O: C, 57.57; H, 4.35; N, 13.43. Found:
C, 57.47; H, 4.27; N, 13.17.
Ethyl N-(4-Chloro-2-cyanophenyl)propanimidate (1h)
Colorless liquid; yield: 97%; bp 125 °C (bath temp)/2.93 mbar.
IR (neat): 2228, 1661 cm–1.
1H NMR (500 MHz): d = 1.11 (t, J = 7.3 Hz, 3 H), 1.37 (t, J = 7.3
Hz, 3 H), 2.16 (q, J = 7.3 Hz, 2 H), 4.28 (q, J = 7.3 Hz, 2 H), 6.78
(d, J = 8.2 Hz, 1 H), 7.43 (dd, J = 8.2, 2.3 Hz, 1 H), 7.53 (d, J = 2.3
Hz, 1 H).
IR (KBr): 3267, 2199, 1616 cm–1.
1H NMR (500 MHz): d = 2.34 (s, 3 H), 4.59 (s, 1 H), 6.07 (br s, 1
H), 7.26 (t, J = 7.8 Hz, 1 H), 7.46 (d, J = 8.2 Hz, 1 H), 7.61 (ddd,
J = 8.2, 7.8, 1.4 Hz, 1 H), 7.67 (dd, J = 7.8, 0.9 Hz, 1 H).
13C NMR: d = 20.58, 69.66, 106.92, 116.04, 119.45, 124.10,
125.49, 133.65, 133.97, 141.49, 156.93.
MS: m/z (%) = 183 (100, [M+]).
Anal. Calcd for C12H13ClN2O: C, 60.89; H, 5.54; N, 11.84. Found:
C, 61.01; H, 5.54; N, 11.72.
Anal. Calcd for C11H9N3: C, 72.11; H, 4.95; N, 22.94. Found: C,
72.04; H, 4.99; N, 22.68.
Methyl N-(4-Chloro-2-cyanophenyl)butanimidate (1i)
Colorless liquid; yield: 92%; bp 130 °C (bath temp)/0.83 mbar.
IR (neat): 2228, 1666 cm–1.
(Z)-2-[2-Ethylquinazolin-4(3H)-ylidene]acetonitrile (2b)
White solid; mp 141–143 °C (hexane–THF).
1H NMR (500 MHz): d = 0.87 (t, J = 7.3 Hz, 3 H), 1.58 (sext,
J = 7.3 Hz, 2 H), 2.15 (t, J = 7.3 Hz, 2 H), 3.85 (s, 3 H), 6.78 (d,
J = 8.7 Hz, 1 H), 7.44 (dd, J = 8.7, 2.7 Hz, 1 H), 7.54 (d, J = 2.7 Hz,
1 H).
IR (KBr): 3250, 2199, 1609 cm–1.
1H NMR (500 MHz): d = 1.37 (t, J = 7.3 Hz, 3 H), 2.65 (q, J = 7.3
Hz, 2 H), 4.53 (s, 1 H), 6.09 (br s, 1 H), 7.26 (ddd, J = 7.8, 7.3, 1.4
Hz, 1 H), 7.46 (d, J = 8.2 Hz, 1 H), 7.62 (ddd, J = 8.2, 7.3, 1.4 Hz,
1 H), 7.67 (dd, J = 7.8, 1.4 Hz, 1 H).
13C NMR: d = 12.70, 28.09, 68.29, 106.95, 115.98, 119.19, 123.99,
125.47, 133.59, 133.97, 141.53, 162.30.
Anal. Calcd for C12H13ClN2O: C, 60.89; H, 5.54; N, 11.84. Found:
C, 60.90; H, 5.42; N, 11.63.
Methyl N-(4,5-Dimethoxy-2-cyanophenyl)acetimidate (1j)
White solid; yield: 95%; bp 150 °C (bath temp)/0.97 mbar; mp 84–
85 °C.
IR (KBr): 2210, 1674, 1608 cm–1.
MS: m/z (%) = 197 (100, [M+]).
Anal. Calcd for C12H11N3: C, 73.07; H, 5.62; N, 21.30. Found: C,
72.96; H, 5.48; N, 21.22.
1H NMR (400 MHz): d = 1.89 (s, 3 H), 3.87 (s, 3 H), 3.88 (s, 3 H),
(Z)-2-[2-Propylquinazolin-4(3H)-ylidene]acetonitrile (2c)
Colorless needles; mp 98–100 °C (hexane–CH2Cl2).
IR (KBr): 3271, 2203, 1614 cm–1.
1H NMR (500 MHz): d = 1.10 (t, J = 7.3 Hz, 3 H), 1.80 (sext,
J = 7.3 Hz, 2 H), 2.61 (t, J = 7.3 Hz, 2 H), 4.59 (s, 1 H), 6.01 (br s,
1 H), 7.26 (dd, J = 7.8, 7.3 Hz, 1 H), 7.46 (d, J = 7.8 Hz, 1 H), 7.62
(ddd, J = 7.8, 7.3, 1.4 Hz, 1 H), 7.67 (dd, J = 7.8, 1.4 Hz, 1 H).
3.89 (s, 3 H), 6.35 (s, 1 H), 6.96 (s, 1 H).
13C NMR: d = 16.43, 53.86, 56.08, 56.28, 95.18, 105.16, 113.70,
117.82, 145.05, 147.97, 153.50, 163.79.
Anal. Calcd for C12H14N2O3: C, 61.53; H, 6.02; N, 11.96. Found: C,
61.56; H, 6.08; N, 11.88.
Ethyl N-(4,5-Dimethoxy-2-cyanophenyl)propanimidate (1k)
Pale-yellow oil; yield: 99%; bp 155 °C (bath temp)/1.33 mbar.
MS: m/z (%) = 211 (70, [M+]), 183 (100).
IR (neat): 2216, 1661, 1607 cm–1.
Anal. Calcd for C13H13N3: C, 73.91; H, 6.20; N, 19.89. Found: C,
73.72; H, 6.19; N, 19.89.
1H NMR (500 MHz): d = 1.13 (t, J = 7.3 Hz, 3 H), 1.37 (t, J = 7.3
Hz, 3 H), 7.18 (q, J = 7.3 Hz, 2 H), 3.86 (s, 3 H), 3.89 (s, 3 H), 4.28
(q, J = 7.3 Hz, 2 H), 6.33 (s, 1 H), 6.95 (s, 1 H).
(Z)-2-[7-Chloro-2-methylquinazolin-4(3H)-ylidene]acetonitrile
(2d)
Colorless needles; mp 132–134 °C (hexane–CH2Cl2).
IR (KBr): 3256, 2206, 1612 cm–1.
Anal. Calcd for C14H18N2O3: C, 64.10; H, 6.92; N, 10.68. Found: C,
64.23; H, 7.02; N, 10.64.
Synthesis 2008, No. 18, 2874–2878 © Thieme Stuttgart · New York

PAPER
Synthesis of (Z)-2-[Quinazolin-4(3H)-ylidene]acetonitriles
MS: m/z (%) = 231 (100, [M+]).
2877
1H NMR (500 MHz): d = 2.34 (s, 3 H), 4.71 (s, 1 H), 6.09 (br s, 1
H), 7.22 (dd, J = 8.2, 1.8 Hz, 1 H), 7.46 (d, J = 1.8 Hz, 1 H), 7.59
(d, J = 8.2 Hz, 1 H).
13C NMR: d = 20.67, 71.74, 104.38, 115.40, 118.76, 123.44,
125.54, 134.38, 140.60, 142.71, 156.06.
Anal. Calcd for C12H10ClN3: C, 62.21; H, 4.35; N, 18.14. Found: C,
62.33; H, 4.36; N, 18.13.
(Z)-2-[6-Chloro-2-propylquinazolin-4(3H)-ylidene]acetonitrile
(2i)
MS: m/z (%) 217 (100, [M+]).
Colorless needles; mp 130 °C (hexane–CH2Cl2).
IR (KBr): 3258, 2199, 1611 cm–1.
Anal. Calcd for C11H8ClN3: C, 60.70; H, 3.70; N, 19.31. Found: C,
60.64; H, 3.92; N, 19.25.
1H NMR (500 MHz): d = 1.09 (t, J = 7.3 Hz, 3 H), 1.80 (sext,
J = 7.3 Hz, 2 H), 2.60 (t, J = 7.3 Hz, 2 H), 4.55 (s, 1 H), 5.99 (br s,
1 H), 7.41 (d, J = 8.7 Hz, 1 H), 7.57 (dd, J = 8.7, 2.3 Hz, 1 H), 7.63
(d, J = 2.3 Hz, 1 H).
(Z)-2-[7-Chloro-2-ethylquinazolin-4(3H)-ylidene]acetonitrile
(2e)
Colorless needles; mp 152–153 °C (hexane–THF).
IR (KBr): 3292, 2205, 1620 cm–1.
13C NMR: d = 13.39, 21.52, 36.32, 69.93, 108.13, 114.82, 118.95,
125.10, 130.75, 132.97, 134.32, 140.20, 160.56.
1H NMR (500 MHz): d = 1.36 (t, J = 7.3 Hz, 3 H), 2.65 (q, J = 7.3
Hz, 2 H), 4.66 (s, 1 H), 6.07 (br s, 1 H), 7.22 (dd, J = 8.7, 1.4 Hz, 1
H), 7.47 (s, 1 H), 7.59 (d, J = 8.7 Hz, 1 H).
13C NMR: d = 12.62, 28.13, 70.26, 104.46, 115.38, 118.57, 123.41,
125.54, 134.34, 140.60, 142.80, 161.50.
MS: m/z (%) = 245 (65, [M+]), 217 (100).
Anal. Calcd for C13H12ClN3: C, 63.55; H, 4.92; N, 17.10. Found: C,
63.34; H, 4.79; N, 16.96.
(Z)-2-[6,7-Dimethoxy-2-methylquinazolin-4(3H)-ylidene]aceto-
nitrile (2j)
Colorless needles; mp 203–205 °C (THF).
IR (KBr): 3347, 2196, 1608 cm–1.
MS: m/z (%) = 231 (100, [M+]).
Anal. Calcd for C12H10ClN3: C, 62.21; H, 4.35; N, 18.14. Found: C,
62.36; H, 4.57; N, 18.08.
(Z)-2-[7-Chloro-2-propylquinazolin-4(3H)-ylidene]acetonitrile
(2f)
1H NMR (500 MHz): d = 2.31 (s, 3 H), 3.90 (s, 3 H), 3.92 (s, 3 H),
4.34 (s, 1 H), 5.85 (br s, 1 H), 6.86 (s, 1 H), 7.02 (s, 1 H).
Colorless needles; mp 124 °C (hexane–CH2Cl2).
IR (KBr): 3244, 2206, 1608 cm–1.
1H NMR (500 MHz): d = 1.09 (t, J = 7.3 Hz, 3 H), 1.77 (sext,
J = 7.3 Hz, 2 H), 2.60 (t, J = 7.3 Hz, 2 H), 4.71 (s, 1 H), 6.06 (br s,
1 H), 7.21 (dd, J = 8.2, 1.8 Hz, 1 H), 7.46 (d, J = 1.8 Hz, 1 H), 7.58
(d, J = 8.2 Hz, 1 H).
MS: m/z (%) = 243 (100, [M+]).
Anal. Calcd for C13H13N3O2: C, 64.19; H, 5.39; N, 17.27. Found: C,
64.00; H, 5.40; N, 17.19.
(Z)-2-[2-Ethyl-6,7-dimethoxyquinazolin-4(3H)-ylidene]acetoni-
trile (2k)
Colorless needles; mp 155–158 °C (hexane–CH2Cl2).
IR (KBr): 3269, 2199, 1601 cm–1.
13C NMR: d = 13.39, 21.49, 36.48, 71.28, 104.25, 115.38, 118.65,
123.15, 125.45, 134.33, 140.64, 142.80, 159.79.
MS: m/z (%) = 245 (51, [M+]), 217 (100).
1H NMR (500 MHz): d = 1.37 (t, J = 7.3 Hz, 3 H), 2.63 (q, J = 7.3
Hz, 2 H), 3.89 (s, 3 H), 3.90 (s, 3 H), 4.27 (s, 1 H), 5.87 (br s, 1 H),
6.85 (s, 1 H), 7.03 (s, 1 H).
13C NMR: d = 12.75, 27.88, 56.41, 56.46, 66.89, 108.57, 113.78,
116.29, 119.48, 136.00, 147.37, 147.49, 163.46, 170.63.
Anal. Calcd for C13H12ClN3: C, 63.55; H, 4.92; N, 17.10. Found: C,
63.38; H, 5.00; N, 17.02.
(Z)-2-[6-Chloro-2-methylquinazolin-4(3H)-ylidene]acetonitrile
(2g)
Colorless needles; mp 130–134 °C (hexane–CH2Cl2).
IR (KBr): 3270, 2210, 1616 cm–1.
1H NMR (500 MHz): d = 2.33 (s, 3 H), 4.55 (s, 1 H), 6.01 (br s, 1
H), 7.40 (d, J = 8.8 Hz, 1 H), 7.57 (dd, J = 8.8, 2.6 Hz, 1 H), 7.63
(d, J = 2.6 Hz, 1 H).
MS: m/z (%) = 257 (100, [M+]).
Anal. Calcd for C14H15N3O2: C, 65.35; H, 5.88; N, 16.33. Found: C,
65.27; H, 6.06; N, 16.46.
(Z)-2-[6,7-Dimethoxy-2-propylquinazolin-4(3H)-ylidene]aceto-
nitrile (2l)
Pale-yellow viscous oil; Rf = 0.37 (Et2O–hexane, 1:1).
IR (neat): 3275, 2201, 1609 cm–1.
13C NMR: d = 20.63, 70.66, 108.11, 114.82, 118.96, 125.15,
130.84, 133.01, 134.33, 140.06, 156.54.
MS: m/z (%) = 217 (65, [M+]), 177 (100).
1H NMR (500 MHz): d = 1.10 (t, J = 7.3 Hz, 3 H), 1.79 (sext,
J = 7.3 Hz, 2 H), 2.58 (t, J = 7.3 Hz, 2 H), 3.90 (s, 3 H), 3.92 (s, 3
H), 4.31 (s, 1 H), 5.85 (br s, 1 H), 6.84 (s, 1 H), 7.02 (s, 1 H).
Anal. Calcd for C11H8ClN3: C, 60.70; H, 3.70; N, 19.31. Found: C,
60.48; H, 3.63; N, 19.21.
MS: m/z (%) = 271 (100, [M+]).
(Z)-2-[6-Chloro-2-ethylquinazolin-4(3H)-ylidene]acetonitrile
(2h)
Colorless needles; mp 152–156 °C (hexane–THF).
Anal. Calcd for C15H17N3O2: C, 66.40; H, 6.32; N, 15.49. Found: C,
66.10; H, 6.38; N, 15.30.
IR (KBr): 3256, 2197, 1611 cm–1.
Acknowledgment
1H NMR (500 MHz): d = 1.36 (t, J = 7.3 Hz, 3 H), 2.64 (q, J = 7.3
Hz, 2 H), 4.49 (s, 1 H), 6.02 (br s, 1 H), 7.41 (d, J = 8.7 Hz, 1 H),
7.58 (dd, J = 8.7, 2.3 Hz, 1 H), 7.64 (d, J = 2.3 Hz, 1 H).
The authors thank Mrs. Miyuki Tanmatsu of this university for de-
termining the mass spectra and performing combustion analyses.
13C NMR: d = 12.66, 27.96, 68.81, 108.36, 114.82, 118.87, 125.38,
130.85, 132.97, 134.30, 140.19, 162.32.
Synthesis 2008, No. 18, 2874–2878 © Thieme Stuttgart · New York

2878
K. Kobayashi et al.
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Synthesis 2008, No. 18, 2874–2878 © Thieme Stuttgart · New York