An efficient synthesis of 4-alkoxy-5,6-dihydro-furo(and -thieno)[2,3-d]pyrimidines using zinc chloride/triethylamine reagent system

Article abstract of DOI:10.1002/jhet.5570450237

(Chemical Equation Presented) The one-pot synthesis of 4-alkoxy-5,6- dihydro-furo(and -thieno)[2,3-d]pyrimidines is described. The reactions of 2-benzamido-4,5-dihydro-3-furan(and -3-thiophene)carbonitriles 1a-d and 2a-c with ethanol and/or methanol in the presence of zinc chloride and triethylamine gave the corresponding 4-alkoxy-5,6-dihydro-furo(and -thieno)[2,3-d]pyrimidines 3a-d, 4a-d, 5a-c and 6a-c.

Full text of DOI:10.1002/jhet.5570450237

Mar-Apr 2008
541
An Efficient Synthesis of 4-Alkoxy-5,6-dihydro-furo(and
-thieno)[2,3-d]pyrimidines Using Zinc Chloride/Triethylamine
Reagent System
Hiroshi Maruoka,* Fumi Okabe and Kenji Yamagata
Faculty of Pharmaceutical Sciences, Fukuoka University,
8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
E-mail: maruoka@fukuoka-u.ac.jp
Received August 8, 2007
OR
R1
R2
CN
R1
R2
ROH, ZnCl2, Et3N
N
NHCOPh
X
X
N
Ph
X = O, S R = Me, Et
The one-pot synthesis of 4-alkoxy-5,6-dihydro-furo(and -thieno)[2,3-d]pyrimidines is described. The
reactions of 2-benzamido-4,5-dihydro-3-furan(and -3-thiophene)carbonitriles 1a-d and 2a-c with ethanol
and/or methanol in the presence of zinc chloride and triethylamine gave the corresponding 4-alkoxy-5,6-
dihydro-furo(and -thieno)[2,3-d]pyrimidines 3a-d, 4a-d, 5a-c and 6a-c.
J. Heterocyclic Chem., 45, 541 (2008).
INTRODUCTION
the intermediate imino derivatives A, which undergo
intramolecular cyclo-condensation to produce the fused
pyrimidines. In keeping with our interest in the synthetic
chemistry of fused pyrimidine derivatives, we now wish
to describe an efficient method for preparing 4-alkoxy-
5,6-dihydro-furo(and -thieno)[2,3-d]pyrimidines by means
of a zinc chloride/triethylamine reagent system.
The fused pyrimidine ring system is a ubiquitous
heterocycle in nature. Owing to the great structural
diversity of biologically active fused pyrimidines such as
quinazoline derivatives, it is not surprising that the fused
pyrimidine ring system has become an important
structural component in many pharmaceutical agents. In
this context, the synthesis [1-16] of fused pyrimidine
derivatives continues to attract attention due to their
biological activities [17-25] and provides an interesting
challenge. For the reasons given above, we have been
interested in the development of the methods for the
construction of fused pyrimidines. In our previous papers
[26-28] we have shown that the reactions of heterocyclic
β-enaminonitriles with various nucleophiles give the 5,6-
RESULTS AND DISCUSSION
An available synthetic route to 4-ethoxy-2-methyl-
quinazoline was developed by Breukink and coworkers
and proceeds from 2-acetamidobenzonitrile [29]. To our
surprise, however, the reactions of 2-benzamido-4,5-
dihydro-3-furancarbonitrile 1a [30] and its thia analogue
2a [31] with sodium ethoxide according to the method of
Breukink et al. [29] produced the desired furo[2,3-d]-
pyrimidine 3a and thieno[2,3-d]pyrimidine 5a in very low
yields. This result indicates that this type of the direct
preparation of fused pyrimidines 3a and 5a starting from
1a and 2a in a one-pot process is not easy. Thus, we
synthesized 3a and 5a by the reaction of 4-chloro-5,6-
dihydro-2-phenylfuro[2,3-d]pyrimidine 7 [28] and its thia
analogue 8 [26] with sodium ethoxide in good yields
(Scheme 2). However, this method has obviously proved
to have a disadvantage such as a long reaction time.
Hence, in order to overcome this limitation, we tried one-
pot synthesis of 3a from 1a and ethanol.
Scheme 1
Nu
R1
R2
CN
Nu!
R1
R2
NH
NHCOPh
X
NHCOPh
X
A
X = O, S
R1 = H, Ph
R2 = H, Me, Ph
H2O
Nu =
NH2
Nu
N
CH2(CN)2
CH2(CN)CO2Me
CH2(CO2Me)2
etc.
R1
R2
We have previously shown that the reactions of
2-amino-4,5-dihydro-3-furan(and -3-thiophene)carbo-
nitriles with active methylene compounds, e.g. ethyl
acetoacetate, dimethyl malonate and diethyl malonate,
Ph
N
X
dihydro-furo(and -thieno)[2,3-d]pyrimidines (Scheme 1).
This reaction probably occurs via the initial attack of
nucleophile to the carbon atom of the cyano group to form
by using
a combination of tin(IV) chloride and
triethylamine afford the fused pyrimidines bearing an

542
H. Maruoka, F. Okabe and K. Yamagata
Vol 45
Scheme 2
Table 1
OEt
One-Pot Synthesis of 4-Alkoxy-5,6-dihydro-
furo(and -thieno)[2,3-d]pyrimidines 3-6
CN
NaOEt [29]
N
EtOH
NHCOMe
Me
Entry
Substrate
Product
Yieid (%)
N
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a
1b
1c
1d
2a
2b
2c
1a
1b
1c
1d
2a
2b
2c
3a
3b
3c
3d
5a
5b
5c
4a
4b
4c
4d
6a
6b
6c
59
44
58
55
89
90
73
57
58
47
47
86
88
86
OEt
CN
NaOEt
N
EtOH
Ph
NHCOPh
X
N
X
(3-11%)
3a:X = O (83% from 7)
5a:X = S (84% from 8)
1a:X = O
2a:X = S
Cl
2 steps
NaOEt
EtOH
N
Ph
X
N
7:X = O [28]
8:X = S [26]
When a mixture of 1a-d and 2a-c with ethanol or
methanol in the presence of zinc chloride and triethylamine
in chloroform or 1,2-dichloroethane was refluxed for
5 hours, the expected 4-alkoxy-5,6-dihydro-2-phenyl-
furo(and -thieno)[2,3-d]pyrimidines 3a-d, 4a-d, 5a-c and
6a-c were obtained in moderate to good yields. The results
are listed in Table 1. The ir spectra of 3-6 lacked
characteristic bands of both, benzoylamino and cyano
group. The 1H nmr spectra of 3 and 5 exhibit a two-proton
quartet near δ 4.5 attributable to the methylene protons of
an ethoxy group and a three-proton triplet near δ 1.3 due to
the methyl protons of an ethoxy group. The 1H nmr spectra
of 4 and 6 show a three-proton singlet near δ 4.0 assignable
to the methyl protons of a methoxy group. Elemental
analyses and spectral data of 3-6 are consistent with the
proposed structures (see experimental section). In addition,
compounds 3a and 5a were shown to be identical with
samples prepared from 4-chloro-5,6-dihydro-2-phenyl-
furo(and -thieno)[2,3-d]pyrimidines (7 and 8) with sodium
Scheme 3
OR
R1
R2
CN
R1
ROH, ZnCl2, Et3N
NH
CHCl3 or ClCH2CH2Cl
reflux, 5 hours
NHCOPh
X
R2
NHCOPh
X
1a-d
2a-c
OR
N
R1 R2
R1
R2
X
R
1, 3,!4
2, 5, 6
O
S
3, 5
4, 6
Et
Me
a
b
c
H
H
Ph
H
H
Me
H
Ph
N
X
d
Ph
3a-d, 4a-d
5a-c, 6a-c
active methine group at the 4-position [28]. Therefore
we anticipated that, by analogy to our earlier work, the
reaction of 1a with ethanol in the presence of Lewis
acid and triethylamine would provide 3a. Thus, we
tested the reactions in the presence of several Lewis
acids. Best result was obtained when 1a was treated
with ethanol in the presence of zinc chloride and
triethylamine, and the expected fused pyrimidine 3a
was isolated in 59% yield (Scheme 3 and entry 1 in
Table 1). The use of other Lewis acids such as
titanium(IV) chloride and tin(IV) chloride was not
successful. Although the reason is not clear at present,
this is probably because the reaction of titanium(IV)
chloride or tin(IV) chloride with ethanol would occur. It
makes us believe that the nucleophilic addition of
ethanol to cyano group and cyclocondensation of the
intermediate imino derivative can only be promoted by
using a couple zinc chloride and triethylamine reagents.
Based on these results, we started the reactions of 1a-d
and 2a-c with ethanol and/or methanol in the presence
of zinc chloride and triethylamine.
ethoxide on the basis of
a mixed melting point
determination and a comparison of the ir spectra.
In conclusion, we have developed a convenient straight-
forward method for the construction of 4-alkoxy-5,6-
dihydrofuro[2,3-d]pyrimidines and their thieno analogues,
proceeding by zinc chloride/triethylamine promoted
nucleophilic addition of alcohol to the cyano group and
cyclocondensation of the non-isolable imino intermediate.
This methodology offers significant advantages with
regard to the simplicity of operation. Functionalized fused
pyrimidines are important synthons in organic synthesis
and for the preparation of biologically active compounds
with interest in medicinal chemistry.
EXPERIMENTAL
All melting points are uncorrected. The 1H and 13C nmr
spectra were recorded on a JEOL JNM-A 500 spectrometer at

Mar-Apr 2008
An Efficient Synthesis of 4-Alkoxy-5,6-dihydro-furo(and -thieno)[2,3-d]pyrimidines
543
500 and 125 MHz, respectively. The H and 13C chemical shifts
(δ) are reported in parts per million (ppm) relative to
tetramethylsilane as internal standard. The positive FAB mass
spectra were obtained on a JEOL JMS-HX 110 spectrometer.
The elemental analyses were performed on a HERAUS CHNO-
RAPID analyzer. The starting materials, 2-benzamido-4,5-
dihydro-3-furan(and -3-thiophene)carbonitriles 1a-d and 2a-c
were easily prepared by previously reported our method [30,31].
General Procedure for the Preparation of 4-Alkoxy-
furo(and -thieno)[2,3-d]pyrimidines 3a-d, 4a-d, 5a-c and 6a-c.
To a stirred solution of 1a-d [30] (10 mmoles) or 2a-c [31] (10
mmoles), ethanol (0.92 g, 20 mmoles) or methanol (0.64 g, 20
mmoles) and triethylamine (2.02 g, 20 mmoles) in chloroform
(20 mL, in the case of the preparation of 3a-d and 4a-d) or in 1,2-
dichloroethane (20 mL, in the case of the preparation of 5a-c and
6a-c) was added zinc chloride (4.08 g, 30 mmoles). After the
mixture was refluxed for 5 hours, a 5% hydrochloric acid
solution (20 mL) was added to the reaction mixture with stirring
and ice-cooling. The resulting mixture was extracted with
chloroform (60 mL). The extract was dried over anhydrous
sodium sulfate and concentrated in vacuo. The residue was
purified by column chromatography on silica gel with chloroform
as the eluent to afford 3a-d, 4a-d, 5a-c and 6a-c.
55%), mp 144-145 ˚C (acetone-petroleum ether); 1H nmr
(deuteriochloroform): δ 1.44 (t, J = 7.0 Hz, 3H, OCH2Me), 3.15
(dd, J = 7.3, 15.6 Hz, 1H, 5-H), 3.62 (dd, J = 9.8, 15.6 Hz, 1H,
5-H), 4.60 (q, J = 7.0 Hz, 2H, OCH2Me), 5.90 (dd, J = 7.3, 9.8
Hz, 1H, 6-H), 7.31-7.46 (m, 8H, Ph-H), 8.43-8.45 ppm (m, 2H,
Ph-H); 13C nmr (deuteriochloroform): δ 14.7 (OCH2Me), 33.4
(C-5), 62.4 (OCH2Me), 83.0 (C-6), 96.8 (C-4a), 125.6, 128.3,
128.7, 130.5, 137.5, 140.9 (Ph-C), 164.2 (C-2), 165.9 (C-4),
176.2 ppm (C-7a); ms: m/z 319 [M+H]+. Anal. Calcd. for
C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C, 75.59; H,
5.83; N, 9.02.
1
5,6-Dihydro-4-methoxy-2-phenylfuro[2,3-d]pyrimidine (4a).
This compound was obtained as colorless needles (1.31 g, 57%),
mp 107-108 ˚C (diethyl ether-petroleum ether); 1H nmr
(deuteriochloroform): δ 3.16 (t, J = 8.9 Hz, 2H, 5-H), 4.10 (s,
3H, OMe), 4.68 (t, J = 8.9 Hz, 2H, 6-H), 7.43-7.44 (m, 3H, Ph-
H), 8.42-8.44 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloro-
form): δ 24.6 (C-5), 53.7 (OMe), 70.1 (C-6), 97.0 (C-4a), 128.2,
128.3, 137.4 (Ph-C), 164.1 (C-2), 166.2 (C-4), 177.0 ppm (C-
7a); ms: m/z 229 [M+H]+. Anal. Calcd. for C13H12N2O2: C,
68.41; H, 5.30; N, 12.27. Found: C, 68.51; H, 5.24; N, 11.97.
5,6-Dihydro-4-methoxy-6-methyl-2-phenylfuro[2,3-d]pyr-
imidine (4b). This compound was obtained as colorless needles
1
4-Ethoxy-5,6-dihydro-2-phenylfuro[2,3-d]pyrimidine (3a).
This compound was obtained as colorless needles (1.42 g, 59%),
mp 103-105 ˚C (diethyl ether-petroleum ether); 1H nmr
(deuteriochloroform): δ 1.44 (t, J = 7.0 Hz, 3H, OCH2Me), 3.17
(t, J = 8.9 Hz, 2H, 5-H), 4.60 (q, J = 7.0 Hz, 2H, OCH2Me), 4.68
(t, J = 8.9 Hz, 2H, 6-H), 7.42-7.44 (m, 3H, Ph-H), 8.40-8.42
ppm (m, 2H, Ph-H); 13C nmr (deuteriochloroform): δ 14.7
(OCH2Me), 24.7 (C-5), 62.3 (OCH2Me), 70.1 (C-6), 97.0 (C-4a),
128.2, 130.4, 137.5 (Ph-C), 163.9 (C-2), 166.0 (C-4), 177.0 ppm
(C-7a); ms: m/z 243 [M+H]+. Anal. Calcd. for C14H14N2O2: C,
69.41; H, 5.82; N, 11.56. Found: C, 69.58; H, 5.94; N, 11.62.
4-Ethoxy-5,6-dihydro-6-methyl-2-phenylfuro[2,3-d]pyrim-
idine (3b). This compound was obtained as colorless columns
(1.40 g, 58%), mp 55-56 ˚C (diethyl ether-petroleum ether); H
nmr (deuteriochloroform): δ 1.52 (d, J = 6.1 Hz, 3H, 6-Me), 2.74
(dd, J = 6.7, 15.6 Hz, 1H, 5-H), 3.29 (dd, J = 9.2, 15.6 Hz, 1H,
5-H), 4.10 (s, 3H, OMe), 5.03-5.08 (m, 1H, 6-H), 7.42-7.44 (m,
3H, Ph-H), 8.42-8.44 ppm (m, 2H, Ph-H); 13C nmr (deuterio-
chloroform): δ 22.0 (6-Me), 37.0 (C-5), 53.6 (OMe), 79.2 (C-6),
97.1 (C-4a), 128.2, 130.5, 137.4 (Ph-C), 164.1 (C-2), 166.2 (C-
4), 176.0 ppm (C-7a); ms: m/z 243 [M+H]+. Anal. Calcd. for
C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.51; H,
5.85; N, 11.48.
5,6-Dihydro-4-methoxy-2,5-diphenylfuro[2,3-d]pyrimidine
(4c). This compound was obtained as colorless needles (1.44 g,
47%), mp 129-131 ˚C (acetone-petroleum ether); 1H nmr
(deuteriochloroform): δ 3.98 (s, 3H, OMe), 4.55 (dd, J = 5.5, 9.2
Hz, 1H, 6-H), 4.67 (dd, J = 5.5, 9.8 Hz, 1H, 5-H), 4.98 (dd, J =
9.2, 9.8 Hz, 1H, 6-H), 7.18-7.20 (m, 2H, Ph-H), 7.26-7.27 (m,
1H, Ph-H), 7.31-7.33 (m, 2H, Ph-H), 7.44-7.46 (m, 3H, Ph-H),
8.45-8.47 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloroform): δ
43.9 (C-5), 53.7 (OMe), 78.2 (C-6), 100.5 (C-4a), 127.2, 127.3,
128.3, 128.4, 128.8, 130.7, 137.2, 141.4 (Ph-C), 164.8 (C-2),
166.5 (C-4), 176.2 ppm (C-7a); ms: m/z 305 [M+H]+. Anal.
Calcd. for C19H16N2O2: C, 74.98; H, 5.30; N, 9.20. Found: C,
74.89; H, 5.39; N, 9.17.
5,6-Dihydro-4-methoxy-2,6-diphenylfuro[2,3-d]pyrimidine
(4d). This compound was obtained as colorless scales (1.43 g,
47%), mp 123-125 ˚C (acetone-petroleum ether); 1H nmr
(deuteriochloroform): δ 3.15 (dd, J = 7.3, 15.8 Hz, 1H, 5-H),
3.62 (dd, J = 9.8, 15.8 Hz, 1H, 5-H), 4.11 (s, 3H, OMe), 5.90
(dd, J = 7.3, 9.8 Hz, 1H, 6-H), 7.33-7.46 (m, 8H, Ph-H), 8.45-
8.47 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloroform): δ 33.3
(C-5), 53.7 (OMe), 83.1 (C-6), 96.8 (C-4a), 125.6, 128.3, 128.4,
128.8, 130.5, 130.6, 137.4, 140.8 (Ph-C), 164.4 (C-2), 166.1 (C-
4), 176.2 ppm (C-7a); ms: m/z 305 [M+H]+. Anal. Calcd. for
C19H16N2O2: C, 74.98; H, 5.30; N, 9.20. Found: C, 74.99; H,
5.36; N, 9.22.
1
(1.13 g, 44%), mp 82-83 ˚C (diethyl ether-petroleum ether); H
nmr (deuteriochloroform): δ 1.44 (t, J = 7.0 Hz, 3H, OCH2Me),
1.52 (d, J = 6.1 Hz, 3H, 6-Me), 2.74 (dd, J = 6.7, 15.6 Hz, 1H, 5-
H), 3.29 (dd, J = 9.2, 15.6 Hz, 1H, 5-H), 4.59 (q, J = 7.0 Hz, 2H,
OCH2Me), 5.03-5.07 (m, 1H, 6-H), 7.41-7.44 (m, 3H, Ph-H),
8.40-8.43 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloroform): δ
14.7 (OCH2Me), 22.1 (6-Me), 32.1 (C-5), 62.3 (OCH2Me), 79.2
(C-6), 97.1 (C-4a), 128.2, 130.4, 137.5 (Ph-C), 163.9 (C-2),
165.9 (C-4), 176.0 ppm (C-7a); ms: m/z 257 [M+H]+. Anal.
Calcd. for C15H16N2O2: C, 70.29; H, 6.29; N, 10.93. Found: C,
70.36; H, 6.48; N, 10.96.
4-Ethoxy-5,6-dihydro-2,5-diphenylfuro[2,3-d]pyrimidine
(3c). This compound was obtained as colorless prisms (1.84 g,
58%), mp 117-118 ˚C (acetone-petroleum ether); 1H nmr
(deuteriochloroform): δ 1.25 (t, J = 7.0 Hz, 3H, OCH2Me), 4.48
(q, J = 7.0 Hz, 2H, OCH2Me), 4.59 (dd, J = 5.5, 8.9 Hz, 1H, 6-
H), 4.67 (dd, J = 5.5, 9.8 Hz, 1H, 5-H), 4.99 (dd, J = 8.9, 9.8 Hz,
1H, 6-H), 7.20-7.33 (m, 5H, Ph-H), 7.43-7.46 (m, 3H, Ph-H),
8.42-8.44 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloroform): δ
14.4 (OCH2Me), 43.8 (C-5), 62.3 (OCH2Me), 78.1 (C-6), 100.6
(C-4a), 127.2, 128.3, 128.4, 128.7, 130.6, 137.4, 141.4 (Ph-C),
164.7 (C-2), 166.2 (C-4), 176.5 ppm (C-7a); ms: m/z 319
[M+H]+. Anal. Calcd. for C20H18N2O2: C, 75.45; H, 5.70; N,
8.80. Found: C, 75.57; H, 5.72; N, 8.87.
4-Ethoxy-5,6-dihydro-2-phenylthieno[2,3-d]pyrimidine
(5a). This compound was obtained as colorless columns (2.30 g,
89%), mp 130-132 ˚C (acetone-petroleum ether); 1H nmr
(deuteriochloroform): δ 1.43 (t, J = 7.0 Hz, 3H, OCH2Me), 3.23-
4-Ethoxy-5,6-dihydro-2,6-diphenylfuro[2,3-d]pyrimidine
(3d). This compound was obtained as colorless scales (1.74 g,

544
H. Maruoka, F. Okabe and K. Yamagata
Vol 45
3.27 (m, 2H, 5-H), 3.39-3.43 (m, 2H, 6-H), 4.56 (q, J = 7.0 Hz,
2H, OCH2Me), 7.41-7.44 (m, 3H, Ph-H), 8.37-8.40 ppm (m, 2H,
Ph-H); 13C nmr (deuteriochloroform): δ 14.6 (OCH2Me), 29.2
(C-5), 30.3 (C-6), 62.1 (OCH2Me), 113.0 (C-4a), 128.2, 130.4,
137.5 (Ph-C), 163.8 (C-2), 164.2 (C-4), 176.4 ppm (C-7a); ms:
m/z 259 [M+H]+. Anal. Calcd. for C14H14N2OS: C, 65.09; H,
5.46; N, 10.84. Found: C, 65.05; H, 5.44; N, 10.93.
4-Ethoxy-5,6-dihydro-6-methyl-2-phenylthieno[2,3-d]pyr-
imidine (5b). This compound was obtained as colorless prisms
(2.45 g, 90%), mp 105-106 ˚C (acetone-petroleum ether); 1H
nmr (deuteriochloroform): δ 1.43 (t, J = 7.0 Hz, 3H, OCH2Me),
1.51 (d, J = 6.7 Hz, 3H, 6-Me), 2.90 (dd, J = 6.0, 16.0 Hz, 1H, 5-
H), 3.37 (dd, J = 8.4, 16.0 Hz, 1H, 5-H), 4.00-4.05 (m, 1H, 6-H),
4.56 (q, J = 7.0 Hz, 2H, OCH2Me), 7.41-7.44 (m, 3H, Ph-H),
8.37-8.40 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloroform): δ
14.6 (OCH2Me), 22.9 (6-Me), 37.5 (C-5), 42.9 (C-6), 62.1
(OCH2Me), 112.6 (C-4a), 128.2, 130.4, 137.5 (Ph-C), 163.8 (C-
2), 164.2 (C-4), 175.7 ppm (C-7a); ms: m/z 273 [M+H]+. Anal.
Calcd. for C15H16N2OS: C, 66.15; H, 5.92; N, 10.29. Found: C,
66.36; H, 5.95; N, 10.46.
(deuteriochloroform): δ 38.9 (C-6), 47.4 (C-5), 53.4 (OMe),
115.8 (C-4a), 126.9, 127.3, 128.3, 128.7, 130.7, 137.2, 142.2
(Ph-C), 164.6 (C-2), 164.8 (C-4), 176.5 ppm (C-7a); ms: m/z
321 [M+H]+. Anal. Calcd. for C19H16N2OS: C, 71.22; H, 5.03; N,
8.74. Found: C, 71.19; H, 5.05; N, 8.66.
The Preparation of 4-Ethoxy-furo(and -thieno)[2,3-d]-
pyrimidines 3a and 5a from 7 and 8. To a solution of sodium
(0.17 g, 7.4 mmoles) in anhydrous ethanol (10 mL) was added 7
[28] (1.16 g, 5 mmoles) or 8 [26] (1.24 g, 5 mmoles) with
stirring. After the mixture was refluxed for 1 hour, a 5%
hydrochloric acid solution (30 mL) was added to the reaction
mixture with stirring and ice-cooling. The precipitate was
isolated by filtration, washed with water, dried and recrystallized
from diethyl ether-petroleum ether (in the case of 3a) or from
acetone-petroleum ether (in the case of 5a) to yield 3a (1.00 g,
83%) and 5a (1.09 g, 84%). These products 3a and 5a were
shown to be identical with samples prepared from 1a and/or 2a
and ethanol in the presence of zinc chloride and triethylamine on
the basis of a mixed melting point determination and a
comparison of the ir spectra.
4-Ethoxy-5,6-dihydro-2,5-diphenylthieno[2,3-d]pyrimidine
(5c). This compound was obtained as colorless prisms (2.45 g,
73%), mp 129-130 ˚C (acetone-petroleum ether); 1H nmr
(deuteriochloroform): δ 1.19 (t, J = 7.0 Hz, 3H, OCH2Me), 3.35
(dd, J = 4.3, 11.3 Hz, 1H, 6-H), 3.92 (dd, J = 9.5, 11.3 Hz, 1H,
6-H), 4.42 (q, J = 7.0 Hz, 2H, OCH2Me), 4.73 (dd, J = 4.3, 9.5
Hz, 1H, 5-H), 7.23-7.31 (m, 5H, Ph-H), 7.42-7.45 (m, 3H, Ph-
H), 8.39-8.41 ppm (m, 2H, Ph-H); 13C nmr (deuteriochloro-
Acknowledgement.
We are grateful to Mr. Hiroshi
Hanazono and Ms. Yukiko Iwase for obtaining mass and nmr
spectra and to Ms. Junko Honda for her valuable help with
elemental analyses.
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δ 14.3 (OCH2Me), 38.6 (C-6), 47.6 (C-5), 62.0
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1
(2.26 g, 88%), mp 87-88 ˚C (diethyl ether-petroleum ether); H
nmr (deuteriochloroform): δ 1.50 (d, J = 6.7 Hz, 3H, 6-Me), 2.90
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