Synthesis of heterocyclic compounds using amidines as their ene-1,1-diamine tautomers. II. Synthesis of 2,3-dihydropyridine, 3,4-dihydropyridine and 3,4-dihydropyrrol-2-one derivatives by the reaction of amidines with α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1002/jhet.5570430512

N-t-Butylacetamidines 1 on heating with methyl vinyl ketone, acrolein or crotonaldehyde gave the 2,3-dihydropyridine derivatives 4, 5 or 6 via N-alkylation of the acetamidines 1. Reaction of amidines 1 with phenyl 1-propenyl ketone, benzalacetone or chalc

Full text of DOI:10.1002/jhet.5570430512

Sep-Oct 2006
1217
Synthesis of Heterocyclic Compounds Using Amidines as Their Ene-
1,1-diamine Tautomers. II. Synthesis of 2,3-Dihydropyridine,
3,4-Dihydropyridine and 3,4-Dihydropyrrol-2-one Derivatives by
the Reaction of Amidines with ꢀ,ꢁ-Unsaturated Carbonyl Compounds
Kunio Ito*, Yoshiko Kizuka and Shogo Ihara
Department of Applied Chemistry, Faculty of Engineering,
Toyo University,
Kujirai, Kawagoe, Saitama 350-8585, Japan
e-mail: chemito@eng.toyo.ac.jp
Received November 9, 2005
R2
R1
R1
R2
R1
COR3
- H2O
CH2
CH
R3
HN
NH
HN
NH2
HN
N
N-t-Butylacetamidines 1 on heating with methyl vinyl ketone, acrolein or crotonaldehyde gave the
2,3-dihydropyridine derivatives 4, 5 or 6 via N-alkylation of the acetamidines 1. Reaction of
amidines 1 with phenyl 1-propenyl ketone, benzalacetone or chalcone gave 3,4-dihydropyridine
derivatives 8, 9 or 10. These were obtained by C-alkylation, achieved by Michael addition of the
acetamidines 1 as their N,C-tautomers ene-1,1-diamines 1' to ꢀ,ꢁ-unsaturated carbonyl compounds,
and subsequent cyclodehydration of adducts. Reaction of 1 with ethyl 3-benzoylacrylate gave 3,4-
dihydropyrrol-2-one derivatives 13.
J. Heterocyclic Chem., 43, 1217 (2006).
In a previous paper, we reported convenient syntheses
was confirmed by elemental analysis, spectroscopic
measurements and X-ray crystal structural analysis.
Although the reaction of unsubstituted amidines or
monosubstituted amidines having a normal alkyl
group on the nitrogen atom and ꢀ,ꢁ-unsaturated
carbonyl compounds gives pyrimidine derivatives [2-
5], N-t-butylacetamidines 1 gave 2,3-dihydropyridine
derivatives 4. Obviously the bulkiness of the N-t-
butyl group in the N-alkylated products 3 acts to
suppress formation of a pyrimidine ring, resulting in
for 4,5-dihydro-3H-pyridin-2-one, 3,4-dihydro-pyrrol-2-
one and 1,3-dihydropyrrol-2-one derivatives by reaction
of monosubstituted amidines with ꢀ,ꢁ-unsaturated esters
[1]. Until that time, there had been no reports for C-
alkylation in which the monosubstituted amidines react
via the N,C-tautomer ene-1,1-diamines. Thus, we
considered that further study on C-alkylation of
monosubstituted amidines was worthwhile. In the present
study, we extended our study to the reaction of ꢀ,ꢁ-
unsaturated carbonyl compounds.
derivatives 4 (Scheme 1).
The suppression of
N-t-Butylbenzylamidine (1a) was heated with
methyl vinyl ketone (2 (R2=H, R3=Me)) at 50˚ for 3
hours in monoglyme. After the solvent and low-
boiling materials were removed under reduced
pressure, N-alkylated product 3a (R2=H, R3=Me),
formed by addition of the amidine 1a via the N,N'-
tautomer azaenamine, was obtained in 95 % yield. A
diglyme solution of the obtained 3a (R2=H, R3=Me)
was heated in a 120˚ oil bath for 2 hours. The solvent
was removed and the residue was vacuum distilled to
obtain the 2,3-dihydropyridine derivative 4a (57 %)
as well as 1a which was formed by the reverse
reaction of 3a. The product 4a was crystallized by
standing at room temperature. The structure of 4a
cyclization by the t-butyl group was also confirmed
by the following experiment. Heating N-t-butylbenz-
amidine and methyl vinyl ketone (2 (R2=H, R3=Me))
at 120˚ for 3 hours produced only the N-alkylated
product 11 (87 %); a cyclization product could not be
isolated. In another reaction, a diglyme solution of 1a
and methyl vinyl ketone (2 (R2=H, R3=Me)) was
heated in a 120˚ oil bath for 2 hours, and 4a was
directly obtained in 67 % yield. Similarly, various N-
t-butylacetamidines 1 were reacted with methyl vinyl
ketone (2 (R2=H, R3=Me)), acrolein (2 (R2=H, R3=
H)) or crotonaldehyde (2 (R2= Me, R3= H)). The
results for the obtained 2,3-dihydropyridine
derivatives 4, 5 and 6 are shown in Table 1.

1218
K. Ito, Y. Kizuka and S. Ihara
Vol 43
Scheme
1
Table 1
R1
R1
CH2
R1
Preparation of Compounds 4, 5 and 6
CH2
CH
N
NH2
HN
NH
HN
NH2
Reaction
Temp Time Yield
Compd.
R1
R2
R3
[˚C]
[h]
[%]
1
1'
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
Ph
H
H
Me
Me
Me
Me
Me
H
120
120
120
120
120
150
150
150
150
150
120
120
120
120
120
2
2
2
2
2
1
1
1
1
2
2
3
2
4
4
67
70
70
68
41
79
69
51
60
43
81
69
67
67
57
R2
R2
COR3
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
Ph
COR3
50˚
150˚
2
H
2
H
R2
R1
H
R1
COR3
CH2
H
COR3
NH
4-Me-C6H
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
Ph
H
H
HN
N
R2
HN
H
H
H
H
7
3
H
H
Me
Me
Me
Me
Me
H
- H2O
120˚ -150˚
- H2O
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
H
R1
Ph
H
R3
N
R2
N
H
a
b
c
d
e
R1
R1
H
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
HN
R2
HN
R3
4-Br-C6H4
4 : R2 = H, R3 = Me
5 : R2 = H, R3 = H
6 : R2 = Me, R3 = H
8 : R2 = Me, R3 = Ph
9 : R2 = Ph, R3 = Me
As a result, 3a (R2=Me, R3=Ph) undergoes the reverse
reaction. A small amount of the N,C-tautomer of the
amidine 1a, that is, ene-1,1-diamine 1'a [1], then reacts
with 2 (R2=Me, R3=Ph) by Michael addition to produce a
C-alkylated product 7a (R2=Me, R3=Ph). Subsequently,
the carbonyl group of 7a (R2=Me, R3=Ph) undergoes
strong nucleophilic attack from the imino nitrogen atom,
and 8a is formed through cyclodehydration. The structure
of 8a was confirmed by elemental analysis and
spectroscopic measurements. Similarly, various N-t-
butylacetamidines 1 were reacted with phenyl 1-propenyl
ketone (2 (R2=Me, R3=Ph)), benzalacetone (2 (R2= Ph,
R3= Me)) or chalcone (2 (R2= Ph, R3=Ph)). The results of
the obtained 3,4-dihydropyridine derivatives 8, 9 and 10
are shown in Table 2.
When a diglyme solution of the amidines 1 and ethyl
3-benzoylacrylate (12) was heated at 120˚, 3,4-dihydro-
pyrrol-2-one derivatives 13 were obtained (Scheme 2,
Table 3). The structure of 13 was confirmed by
elemental analysis, spectroscopic measurements and X-
ray crystal structural analysis. The compounds 13 were
formed by Michael addition of the amidines 1 as their
N,C-tautomer ene-1,1-diamines 1' to ꢀ,ꢁ-unsaturated
ketone 12 and subsequent cyclization with elimination
of ethyl alcohol.
10 : R2 = Ph, R3 = Ph
Ph
COMe
HN
N
11
Reaction of N-t-butylacetamidines 1 with phenyl 1-
propenyl ketone, benzalacetone or chalcone, in which the
carbonyl groups is less electrophilic than that of methyl
vinyl ketone, acrolein and crotonaldehyde [6], gave
products resulting from C-alkylation of the amidines, as
has been previously reported for ꢀ,ꢁ-unsaturated esters
[1]. That is, a diglyme solution of N-t-butylbenzylamidine
(1a) and phenyl 1-propenyl ketone (2 (R2=Me, R3=Ph))
was heated in a 150˚ oil bath for 3 hours. The solvent
was removed and deposited crystals were collected to
obtain the 3,4-dihydropyridine derivative 8a (60 %). The
formation of 8a is considered to proceed as follows
(Scheme 1). Although this reaction tends toward N-
alkylation, cyclization of the N-alkylated product 3a
(R2=Me, R3=Ph) does not take place because the carbonyl
group in the N-alkylated product has low electrophilicity.

Sep-Oct 2006
Synthesis of Heterocyclic Compounds Using Amidines
1219
Table 2
Michael adducts 7 gave 3,4-dihydropyridine derivatives 8,
9 and 10. In addition, 3,4-dihydropyrrol-2-one deriv-
atives 13 were obtained by reaction of the acetamidines 1
with ethyl 3-benzoylacrylate 12.
Preparation of Compounds 8, 9 and 10
Reaction
Temp Time
Compd.
R1
R2
R3
Yield
[%]
[˚C]
[h]
8a
8b
8c
Ph
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
3
3
3
3
3
4
4
4
3
3
3
4
3
3
3
60
58
49
61
55
67
43
34
54
49
72
62
78
91
71
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
Ph
8d
8e
9a
9b
9c
9d
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
Ph
9e
10a
10b
10c
10d
10e
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
Scheme
2
COPh
COPh
R1
R1
COPh
EtO2C
12
CO2Et
NH
1
HN
HN
O
N
- EtOH
120˚
Figure 1 Crystal structure of compound 4a.
13
Acetamidines 1 having a t-butyl group on the
nitrogen atom were reacted with methyl vinyl ketone
(2 (R2=H, R3=Me)), acrolein (2 (R2=H, R3= H)) or
crotonaldehyde (2 (R2= Me, R3= H)). The amidines
1
reacted as their N,N'-tautomer azaenamines,
forming N-alkylated products 3. Subsequent cyclo-
dehydration of the N-alkylated products 3 gave the
2,3-dihydropyridine derivatives 4, 5 and 6.
In
contrast, in reaction with phenyl 1-propenyl ketone (2
(R2=Me, R3=Ph)), benzalacetone (2 (R2= Ph, R3= Me))
or chalcone (2 (R2= Ph, R3=Ph)), the same
acetamidines 1 reacted as their N,C-tautomer ene-1,1-
diamines 1'. Thus, the amidines 1 were C-alkylated
by Michael addition to the ꢀ,ꢁ-unsaturated carbonyl
compounds. Subsequent cyclodehydration of the
Figure 2 Crystal structure of compound 13a
Table 3
Preparation of Compounds 13
EXPERIMENTAL
Reaction
R1
Temp[˚C]
Time[h]
Yield[%]
All melting points and boiling points are uncorrected. The ir
spectra were recorded on a Horiba FT-720 spectrometer in
Compd.
13a
13b
13c
13d
13e
Ph
120
120
120
120
120
1
2
2
2
2
85
78
77
77
49
1
potassium bromide pellets unless otherwise noted. The H nmr
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
data were obtained with a JEOL JNM-EX400 (400 MHz) or a
JEOL JNM-ECX500M (500 MHz) spectrometer in deuterio-
chloroform by using tetramethylsilane as an internal standard.

1220
K. Ito, Y. Kizuka and S. Ihara
Vol 43
pressure, the resulting residue was distilled to give the products
4, 5 or 6. The products (except 5b) has solidified by the
standing. All the products obtaind were of satisfactory purity as
judged by 1H nmr spectroscopy. Analytical samples were
prepared by recrystallization from ethyl acetate.
Mass spectra were measured with a Shimadzu GCMS-QP5050A
spectrometer at 70 eV of ionization energy by use of a direct-inlet
system. Elemental analyses were performed by using a Perkin-
Elmer 2400 II CHN Analyzer. X-ray structure determinations were
performed on Rigaku RAXIS-RAPID diffractometer, at the X-ray
Research Laboratory, Rigaku Corporation.
6-t-Butylamino-4-methyl-5-phenyl-2,3-dihydropyridine (4a).
N-t-Butylacetamidines
1 and N-t-Butylbenzamidine were
This compound was obtained as pale yellow needles, mp
94.0-94.5˚; bp 108.0-110.0˚ (0.35 mmHg); ir: 3429, 1658, 1597,
1512, 1448 cm-1; 1H nmr: ꢀ 1.24 (9H, s, C(CH3)3), 1.68 (3H, s,
CH3), 2.12 and 3.48 (each 2H, t, J=7.6 Hz, CH2), 3.50 (1H, br s,
NH), 7.11-7.38 (5H, m, aromatic); ms: (CI) m/z 243 (MH+).
Anal. Calcd. for C16H22N2: C, 79.29; H, 9.15; N, 11.56.
Found: C, 79.36; H, 9.28; N, 11.72.
prepared by the method of Cooper and Partridge [7]. Methyl
vinyl ketone, acrolein, crotonaldehyde, pheyl 1-propenyl ketone,
benzalacetone, chalcone and ethyl benzoylacrylate were
commercially available and used without further purification.
N-t-Butyl-N'-(3-oxobutyl)-2-phenylacetamidine (3a (R2=H,
R3=Me)).
X-Ray structure determinetion of compound 4a.
A solution containing N-t-butylbenzylamidine (1a) (9.51 g,
50.0 mmoles) and methyl vinyl ketone (2 (R2=H, R3=Me)) (4.21
g, 60.0 mmoles) in monoglyme (50 ml) was heated 50˚ for 3
hours. The solvent and the low boiling materials were removed
under reduced pressure (at 0.12 mmHg), maintaining the bath
temperature below 50˚, leaving 12.32 g (95 %) of N-alkylation
product 3a (R2=H, R3=Me) as a pale yellow liquid. This product
obtained was of satisfactory purity as judged by 1H nmr
spectroscopy, which was used without further purification; ir
(liquid film): 3406, 1709, 1645, 1500, 1450 cm-1; 1H nmr: ꢀ
1.28 (9H, s, C(CH3)3), 2.15 (3H, s, CH3), 2.58 and 3.45 (each
2H, t, J=6.6 Hz, CH2), 3.47 (2H, s, CH2), 3.70 (1H, br s, NH),
7.16-7.31 (5H, m, aromatic); ms: (CI) m/z 261 (MH+).
Crystal of 4a suitable for the structure analysis were obtained
by recrystallization from ethyl acetate. The measurements were
made on a Rigaku RAXIS RAPID imaging plate area detector
with graphite monochromated Cu-Kꢁ (ꢂ=1.54182 Å) radiation.
The crystal structure was solved by direct methods (SIR97) and
expanded using Fourier techniques (DIRDIF99)ꢀ(Figure 1).
Crystal data: Empirical formula C16H22N2; Formula weight
242.36; Crystal dimensions 0.20x0.12x0.07 mm; Crystal system
orthorhombic; Lattice parameters a=6.588(5) Å, b=7.3586(6) Å,
c=30.270(2) Å, V=1438.64(20) Å3; Space group P212121 (#19);
Z value 4; Dcalc=1.119 g/cm3; F000=528.00; μ(CuKꢀ)=5.004 cm-1;
No. of reflections 2574; Residuals: R1 (1>2.00ꢁ(I))=0.0343,
R=0.0406, wR2=0.0860; Goodness of fit indicator 1.080.
Anal. Calcd. for C16H24N2O: C, 73.81; H, 9.29; N, 10.76.
Found: C, 73.74; H, 9.51; N, 11.13.
6-t-Butylamino-4-methyl-5-(4-methylphenyl)-2,3-dihydro-
pyridine (4b).
Conversion to 2,3-Dihydropyridine Derivative 4a of N-
Alkylation Product 3a (R2=H, R3=Me).
This compound was obtained as colorless prisms, mp 92.5-
93.0˚; bp 122.0-124.0˚ (0.55 mmHg); ir: 3427, 1662, 1603,
1510, 1446 cm-1; 1H nmr: ꢀ 1.24 (9H, s, C(CH3)3), 1.67 (3H, s,
CH3), 2.10 and 3.46 (each 2H, t, J=7.6 Hz, CH2), 2.37 (3H, s,
CH3), 3.56 (1H, br s, NH), 7.00 and 7.16 (each 2H, d, J=8.0 Hz,
aromatic); ms: (CI) m/z 257 (MH+).
A solution of N-alkylation product 3a (R2=H, R3=Me) (7.82 g,
30.0 mmoles) in diglyme (60 ml) was heated with stirring at
120˚ for 2 hours. Removal of the solvent under reduced
pressure and distillation of the residue gave 1.71 g (30 %) of the
acetamidine 1a and 4.41 g (57 %) of the 2,3-dihydropyridine
derivatives 4a, and both have solidified by the standing.
Anal. Calcd. for C17H24N2: C, 79.64; H, 9.43; N, 10.93.
Found: C, 79.42; H, 9.75; N, 10.98.
N-t-Butyl-N'-(3-oxobutyl)-benzamidine (11).
6-t-Butylamino-4-methyl-5-(4-methoxyphenyl)-2,3-dihydro-
pyridine (4c).
A solution containing N-t-butylbenzamidine (3.53 g, 20.0
mmoles) and methyl vinyl ketone (2 (R2=H, R3=Me)) (1.68 g,
24.0 mmoles) in diglyme (40 ml) was heated with stirring at
120˚ for 3 hours. After removal of the solvent under reduced
pressure, the residual solid was recrystallized from ethyl acetate
to give 4.29 g (87 %) of 11 as colorless prisms, mp 74.5-75.0˚;
ir: 3379, 1705, 1631, 1599, 1522, 1442 cm-1; 1H nmr: ꢀ 1.38
(9H, s, C(CH3)3), 2.15 (3H, s, CH3), 2.52 and 3.29 (each 2H, t,
J=6.6 Hz, CH2), 3.79 (1H, br s, NH), 7.21-7.37 (5H, m,
aromatic); ms: (CI) m/z 247 (MH+).
This compound was obtained as a pale orange powder, mp
76.0-77.0˚; bp 140.0-144.0˚ (0.55 mmHg); ir: 3431, 1660, 1606,
1510, 1450 cm-1; 1H nmr: ꢀ 1.24 (9H, s, C(CH3)3), 1.68 (3H, s,
CH3), 2.01 and 3.46 (each 2H, t, J=7.7 Hz, CH2), 3.55 (1H, br s,
NH), 3.83 (3H, s, CH3O), 6.90 and 7.04 (each 2H, d, J=8.5 Hz,
aromatic); ms: (CI) m/z 273 (MH+).
Anal. Calcd. for C17H24N2O: C, 74.96; H, 8.88; N, 10.28.
Found: C, 74.75; H, 8.88; N, 10.10.
Anal. Calcd. for C15H22N2O: C, 73.13; H, 9.00; N, 11.37.
Found: C, 73.06; H, 9.24; N, 11.35.
6-t-Butylamino-5-(4-chlorophenyl)-4-methyl-2,3-dihydro-
pyridine (4d).
2,3-Dihydropyridines 4, 5 and 6.
This compound was obtained as colorless prisms, mp 112.5-
113.5˚; bp 135.0-137.0˚ (1.10 mmHg); ir: 3429, 1660, 1604,
1510, 1489, 1448 cm-1; 1H nmr: ꢀ 1.24 (9H, s, C(CH3)3), 1.67
(3H, s, CH3), 2.11 and 3.46 (each 2H, t, J=7.6 Hz, CH2), 3.38
(1H, br s, NH), 7.07 and 7.35 (each 2H, d, J=8.3 Hz, aromatic);
ms: (CI) m/z 277 (MH+).
A solution containing N-t-butylacetamidines 1 (30.0 mmoles)
and methyl vinyl ketone (2 (R2=H, R3=Me)), acrolein (2 (R2=H,
R3=H)) or crotonaldehyde (2 (R2=Me, R3=H)) (36.0 mmoles) in
diglyme (60 ml) was heated with stirring at the temperature
indicated in Table 1. After removal of the solvent under reduced

Sep-Oct 2006
Synthesis of Heterocyclic Compounds Using Amidines
1221
Anal. Calcd. for C16H21ClN2: C, 69.43; H, 7.65; N, 10.12.
Found: C, 69.51; H, 7.84; N, 10.08.
Anal. Calcd. for C15H19BrN2: C, 58.64; H, 6.23; N, 9.12.
Found: C, 58.83; H, 6.28; N, 9.24.
5-(4-Bromophenyl)-6-t-butylamino-4-methyl-2,3-dihydro-
pyridine (4e).
6-t-Butylamino-2-methyl-5-phenyl-2,3-dihydropyridine (6a).
This compound was obtained as colorless prisms, mp 43.5-
44.5˚; bp 107.0-110.0˚ (1.00 mmHg); ir: 3438, 1649, 1591,
1506, 1448 cm-1; 1H nmr: ꢀ 1.25 (3H, d, J=6.8 Hz, CH3), 1.33
(9H, s, C(CH3)3), 1.87 (1H, ddd, J=16.8, 11.6, 3.7 Hz, CH2),
2.23 (1H, ddd, J=16.8, 5.6, 5.6 Hz, CH2), 3.50 (1H, m, CH3CH)
3.66 (1H, br s, NH), 6.24 (1H, dd, J=5.6, 3.7 Hz, CH), 7.23-7.34
(5H, m, aromatic); ms: (CI) m/z 243 (MH+).
This compound was obtained as a white powder, mp 124.0-
125.0˚; ir: 3427, 1660, 1603, 1510, 1445, 1448 cm-1; 1H nmr: ꢀ
1.25 (9H, s, C(CH3)3), 1.67 (3H, s, CH3), 2.11 and 3.46 (each
2H, t, J=7.6 Hz, CH2), 3.37 (1H, br s, NH), 7.01 and 7.50 (each
2H, d, J=8.3 Hz, aromatic); ms: (CI) m/z 321and 323 (MH+).
Anal. Calcd. for C16H21BrN2: C, 59.82; H, 6.59; N, 8.72.
Found: C, 59.94; H, 6.62; N, 8.70.
Anal. Calcd. for C16H22N2: C, 79.29; H, 9.15; N, 11.56.
Found: C, 79.25; H, 9.39; N, 11.58.
6-t-Butylamino-5-phenyl-2,3-dihydropyridine (5a).
6-t-Butylamino-2-methyl-5-(4-methylphenyl)-2,3-dihydro-
pyridine (6b).
This compound was obtained as a white powder, mp 41.5-
42.5˚; bp 112.0-114.0˚ (0.40 mmHg); ir: 3433, 1647, 1591,
1508, 1450 cm-1; 1H nmr: ꢀ 1.32 (9H, s, C(CH3)3), 2.15 (2H, td,
J=7.6, 4.6 Hz, CH2), 3.45 (2H, t, J=7.6 Hz, CH2), 3.77 (1H, br s,
NH), 6.37 (1H, t, J=4.6 Hz, CH), 7.26-7.36 (5H, m, aromatic);
ms: (CI) m/z 229 (MH+).
This compound was obtained as pale yellow prisms, mp 54.0-
55.0˚; bp 115.0-117.0˚ (0.45 mmHg); ir: 3437, 1651, 1593,
1506, 1448 cm-1; 1H nmr: ꢀ 1.24 (3H, d, J=6.7 Hz, CH3), 1.33
(9H, s, C(CH3)3), 1.86 (1H, ddd, J=16.8, 11.5, 3.7 Hz, CH2),
2.23 (1H, ddd, J=16.8, 5.6, 5.6 Hz, CH2), 2.35 (3H, s, CH3), 3.49
(1H, m, CH3CH) 3.70 (1H, br s, NH), 6.22 (1H, dd, J=5.6, 3.7
Hz, CH), 7.14 (4H, s, aromatic); ms: (CI) m/z 257 (MH+).
Anal. Calcd. for C17H24N2: C, 79.64; H, 9.43; N, 10.93.
Found: C, 79.79; H, 9.53; N, 10.68.
Anal. Calcd. for C15H20N2: C, 78.90; H, 8.83; N, 12.27.
Found: C, 78.68; H, 9.05; N, 12.17.
6-t-Butylamino-5-(4-methylphenyl)-2,3-dihydropyridine (5b).
This compound was obtained as a colorless liquid, bp 117.0-
119.0˚ (0.70 mmHg); ir: (liquid film) 3437, 1649, 1589, 1510,
1450 cm-1; 1H nmr: ꢀ 1.32 (9H, s, C(CH3)3), 2.13 (2H, td, J=7.6,
4.6 Hz, CH2), 2.36 (3H, s, CH3), 3.44 (2H, t, J=7.6 Hz, CH2),
3.82 (1H, br s, NH), 6.34 (1H, t, J=4.6 Hz, CH), 7.15 (5H, s,
aromatic); ms: (CI) m/z 243 (MH+).
6-t-Butylamino-5-(4-methoxyphenyl)-2-methyl-2,3-dihydro-
pyridine (6c).
This compound was obtained as orange prisms, mp 65.0-
66.5˚; bp 138.0-140.0˚ (1.10 mmHg); ir: 3406, 1645, 1608,
1583, 1508, 1442 cm-1; 1H nmr: ꢀ 1.24 (3H, d, J=6.6 Hz, CH3),
1.33 (9H, s, C(CH3)3), 1.86 (1H, ddd, J=16.8, 11.7, 3.7 Hz,
CH2), 2.23 (1H, ddd, J=16.8, 5.6, 5.6 Hz, CH2), 3.49 (1H, m,
CH3CH) 3.70 (1H, br s, NH), 3.82 (3H, s, CH3O), 6.19 (1H, dd,
J=5.6, 3.7 Hz, CH), 6.88 and 7.18 (each 2H, d, J=8.8 Hz,
aromatic); ms: (CI) m/z 273 (MH+).
Anal. Calcd. for C16H22N2: C, 79.29; H, 9.15; N, 11.56.
Found: C, 78.95; H, 9.19; N, 11.28.
6-t-Butylamino-5-(4-methoxyphenyl)-2,3-dihydropyridine (5c).
This compound was obtained as pale orange prisms, mp
76.5-77.5˚; bp 146-148.0˚ (1.10 mmHg); ir: 3442, 1649,
1608, 1591, 1508, 1466 cm-1; 1H nmr: ꢀ 1.33 (9H, s,
C(CH3)3), 2.13 (2H, td, J=7.6, 4.6 Hz, CH2), 3.44 (2H, t,
J=7.6 Hz, CH2), 3.81 (1H, br s, NH), 3.83 (3H, s, CH3O),
6.32 (1H, t, J=4.6 Hz, CH), 6.89 and 7.19 (each 2H, d, J=8.5
Hz, aromatic); ms: (CI) m/z 259 (MH+).
Anal. Calcd. for C17H24N2O: C, 74.96; H, 8.88; N, 10.28.
Found: C, 74.93; H, 9.04; N, 10.34.
6-t-Butylamino-5-(4-chlorophenyl)-2-methyl-2,3-dihydro-
pyridine (6d).
Anal. Calcd. for C16H22N2O: C, 74.38; H, 8.58; N, 10.84.
Found: C, 74.03; H, 8.90; N, 10.75.
This compound was obtained as colorless prisms, mp 66.0-67.0˚;
bp 125.0-127.0˚ (0.40 mmHg); ir: 3442, 1647, 1587, 1508, 1489,
1448 cm-1; 1H nmr: ꢀ 1.24 (3H, d, J=6.9 Hz, CH3), 1.33 (9H, s,
C(CH3)3), 1.87 (1H, ddd, J=16.6, 11.5, 3.4 Hz, CH2), 2.24 (1H,
ddd, J=16.6, 5.7, 5.7 Hz, CH2), 3.49 (1H, m, CH3CH) 3.55 (1H, br
s, NH), 6.25 (1H, dd, J=5.7, 3.4 Hz, CH), 7.20 and 7.31 (each 2H,
d, J=8.6 Hz, aromatic); ms: (CI) m/z 277 (MH+).
6-t-Butylamino-5-(4-chlorophenyl)-2,3-dihydropyridine (5d).
This compound was obtained as colorless prisms, mp 67.5-
68.5˚; bp 145.0-148.0˚ (1.70 mmHg); ir: 3438, 1651, 1597,
1508, 1483, 1448 cm-1; 1H nmr: ꢀ 1.32 (9H, s, C(CH3)3), 2.14
(2H, td, J=7.6, 4.6 Hz, CH2), 3.44 (2H, t, J=7.6 Hz, CH2), 3.64
(1H, br s, NH), 6.36 (1H, t, J=4.6 Hz, CH), 7.20 and 7.32 (each
2H, d, J=8.4 Hz, aromatic); ms: (CI) m/z 263 (MH+).
Anal. Calcd. for C16H21ClN2: C, 69.43; H, 7.65; N, 10.12.
Found: C, 69.69; H, 7.76; N, 10.24.
5-(4-Bromophenyl)-6-t-butylamino-2-methyl-2,3-dihydro-
pyridine (6e).
Anal. Calcd. for C15H19ClN2: C, 68.56; H, 7.29; N, 10.66.
Found: C, 68.79; H, 7.55; N, 10.79.
This compound was obtained as colorless prisms, mp 82.0-
83.0˚; bp 137.0-139.0˚ (0.45 mmHg); ir: 3440, 1645, 1587,
1510, 1485, 1450 cm-1; 1H nmr: ꢀ 1.24 (3H, d, J=6.9 Hz, CH3),
1.33 (9H, s, C(CH3)3), 1.86 (1H, ddd, J=16.6, 11.5, 3.4 Hz,
CH2), 2.24 (1H, ddd, J=16.6, 5.7, 5.7 Hz, CH2), 3.48 (1H, m,
CH3CH) 3.55 (1H, br s, NH), 6.26 (1H, dd, J=5.7, 3.4 Hz, CH),
7.14 and 7.47 (each 2H, d, J=8.6 Hz, aromatic); ms: (CI) m/z
321 and 323 (MH+).
5-(4-Bromophenyl)-6-t-butylamino-2,3-dihydropyridine (5e).
This compound was obtained as a white powder, mp 79.0-
80.0˚; ir: 3433, 1655, 1637, 1597, 1572, 1514, 1481, 1446 cm-1;
1H nmr: ꢀ 1.32 (9H, s, C(CH3)3), 2.14 (2H, td, J=7.6, 4.6 Hz,
CH2), 3.44 (2H, t, J=7.6 Hz, CH2), 3.64 (1H, br s, NH), 6.37
(1H, t, J=4.6 Hz, CH), 7.14 and 7.48 (each 2H, d, J=8.3 Hz,
aromatic); ms: (CI) m/z 307 and 309 (MH+).

1222
K. Ito, Y. Kizuka and S. Ihara
Vol 43
Anal. Calcd. for C16H21BrN2: C, 59.82; H, 6.59; N, 8.72.
Found: C, 59.90; H, 6.54; N, 8.80.
This compound was obtained as colorless prisms, mp 162.0-
163.5˚; ir: 3425, 1655, 1593, 1512, 1481, 1446 cm-1; 1H nmr: ꢀ
1.02 (3H, d, J=6.9 Hz, CH3), 1.44 (9H, s, C(CH3)3), 2.54 (1H,
dqd, J=8.6, 6.9, 4.6 Hz, CH), 2.92 (1H, d, J=8.6 Hz, CH), 3.99
(1H, br s, NH), 5.58 (1H, d, J=4.6 Hz, CH), 7.04-7.44 and 7.83-
7.85 (9H, m, aromatic); ms: (CI) m/z 397 and 399 (MH+).
Anal. Calcd. for C22H25BrN2: C, 66.50; H, 6.34; N, 7.05.
Found: C, 66.14; H, 6.05; N, 7.09.
3,4-Dihydropyridines 8.
A solution containing N-t-butylacetamidines 1 (20.0 mmoles)
and phenyl 1-propenyl ketone (2 (R2=Me, R3=Ph)) (24.0
mmoles) in diglyme (40 ml) was heated with stirring at 150˚ for
3 hours. After removal of the solvent under reduced pressure,
deposited crystals were collected and washed with small amount
of ethyl acetate to give 8. All the products obtained were of
satisfactory purity as judged by 1H nmr spectroscopy.
Analytical samples were prepared by further recrystallization
from ethyl acetate.
3,4-Dihydropyridines 9.
A solution containing N-t-butylacetamidines 1 (30.0 mmoles)
and benzalacetone (2 (R2=Ph, R3=Me)) (33.0 mmoles) in
diglyme (60 ml) was heated with stirring at 150˚ for the time
indicated in Table 2. After removal of the solvent under reduced
pressure, the resulting residue was distilled to give 9. The
product 9c, 9d and 9e had solidified by the standing. All the
2-t-Butylamino-4-methyl-3,6-diphenyl-3,4-dihydropyridine
(8a).
1
products obtained were of satisfactory purity as judged by H
This compound was obtained as colorless prisms, mp 106.5-
107.5˚; ir: 3425, 1610, 1587, 1520, 1493, 1542 cm-1; 1H nmr: ꢀ
1.00 (3H, d, J=6.9 Hz, CH3), 1.42 (9H, s, C(CH3)3), 2.64 (1H,
dqd, J=9.7, 6.9, 4.0 Hz, CH), 2.97 (1H, d, J=9.8 Hz, CH), 4.01
(1H, br s, NH), 5.61 (1H, d, J=4.0 Hz, CH), 7.17-7.36 and 7.84-
7.87 (10H, m, aromatic); ms: (CI) m/z 319 (MH+).
nmr spectroscopy. Samples for analysis were recrystallized
from ethyl acetate.
2-t-Butylamino-6-methyl-3,4-diphenyl-3,4-dihydropyridine
(9a).
This compound was obtained as pale yellow liquid, bp 150.0-
153.0˚ (0.40 mmHg); ir (liquid film): 3429, 1637, 1595, 1516,
1452 cm-1; 1H nmr: ꢀ 1.35 (9H, s, C(CH3)3), 1.98 (3H, d, J=1.2
Hz, CH3), 3.21 (1H, d, J=6.1 Hz, CH), 3.41 (1H, dd, J=6.1, 4.9
Hz, CH), 3.89 (1H, br s, NH), 4.86 (1H, dq, J=4.9, 1.2 Hz, CH),
7.14-7.29 (10H, m, aromatic); ms: (CI) m/z 319 (MH+).
Anal. Calcd. for C22H26N2: C, 82.97; H, 8.23; N, 8.80. Found:
C, 83.34; H, 8.22; N, 8.97.
Anal. Calcd. for C22H26N2: C, 82.97; H, 8.23; N, 8.80. Found:
C, 82.87; H, 8.24; N, 8.72.
2-t-Butylamino-4-methyl-3-(4-methylphenyl)-6-phenyl-3,4-
dihydropyridine (8b).
This compound was obtained as colorless prisms, mp 138.5-
140.0˚; ir: 3423, 1637, 1593, 1513, 1491, 1446 cm-1; 1H nmr: ꢀ
0.99 (3H, d, J=6.9 Hz, CH3), 1.42 (9H, s, C(CH3)3), 2.33 (3H, s,
CH3), 2.61 (1H, dqd, J=10.3, 6.9, 4.0 Hz, CH), 2.93 (1H, d, J=10.3
Hz, CH), 4.05 (1H, br s, NH), 5.60 (1H, d, J=4.0 Hz, CH), 7.06-
7.35 and 7.85-7.87 (9H, m, aromatic); ms: (CI) m/z 333 (MH+).
Anal. Calcd. for C23H28N2: C, 83.09; H, 8.49; N, 8.48. Found:
C, 83.48; H, 8.50; N, 8.60.
2-t-Butylamino-6-methyl-3-(4-methylphenyl)-4-phenyl-3,4-
dihydropyridine (9b).
This compound was obtained as pale yellow liquid, bp 172.0-
175.0˚ (0.70 mmHg); ir (liquid film): 3425, 1639, 1595, 1514,
1450 cm-1; 1H nmr: ꢀ 1.34 (9H, s, C(CH3)3), 1.98 (3H, d, J=1.1
Hz, CH3), 2.30 (3H, s, CH3), 3.18 (1H, d, J=6.3 Hz, CH), 3.38
(1H, dd, J=6.3, 5.2 Hz, CH), 3.92 (1H, br s, NH), 4.85 (1H, dq,
J=5.2, 1.1 Hz, CH), 7.03-7.22 (9H, m, aromatic); ms: (CI) m/z
333 (MH+).
2-t-Butylamino-3-(4-methoxyphenyl)-4-methyl-6-phenyl-3,4-
dihydropyridine (8c).
This compound was obtained as pale yellow prisms, mp
144.5-145.5˚; ir: 3417, 1608, 1585, 1510, 1492, 1448 cm-1; 1H
nmr: ꢀ 0.98 (3H, d, J=6.9 Hz, CH3), 1.42 (9H, s, C(CH3)3), 2.60
(1H, dqd, J=10.3, 6.9, 4.0 Hz, CH), 2.93 (1H, d, J=10.3 Hz,
CH), 3.78 (3H, s, CH3O), 4.06 (1H, br s, NH), 5.61 (1H, d, J=4.0
Hz, CH), 6.84-7.35 and 7.85-7.87 (9H, m, aromatic); ms: (CI)
m/z 349 (MH+).
Anal. Calcd. for C23H28N2: C, 83.09; H, 8.49; N, 8.43. Found:
C, 83.07; H, 8.49; N, 8.42.
2-t-Butylamino-3-(4-methoxyphenyl)-6-methyl-4-phenyl-3,4-
dihydropyridine (9c).
This compound was obtained as colorless prisms, mp 143.5-
144.5˚; bp 180.0-183.0˚ (0.30 mmHg); ir: 3415, 1637, 1589,
1529, 1508, 1452 cm-1; 1H nmr: ꢀ 1.35 (9H, s, C(CH3)3), 1.99
(3H, dd, J=1.4, 1.3 Hz, CH3), 3.18 (1H, d, J=6.8 Hz, CH), 3.39
(1H, ddq, J=6.8, 4.7, 1.4 Hz, CH), 3.78 (3H, s, CH3O), 3.94 (1H,
br s, NH), 4.88 (1H, dq, J=4.7, 1.3 Hz, CH), 6.81 and 7.05 (each
2H, d, J=8.6 Hz, aromatic), 7.13-7.25 (5H, m, aromatic); ms:
(CI) m/z 349 (MH+).
Anal. Calcd. for C23H28N2O: C, 79.27; H, 8.10; N, 8.04.
Found: C, 79.58; H, 8.20; N, 8.20.
2-t-Butylamino-3-(4-chlorophenyl)-4-methyl-6-phenyl-3,4-
dihydropyridine (8d).
This compound was obtained as colorless prisms, mp 158.0-
159.5˚; ir: 3425, 1655, 1591, 1513, 1485, 1446 cm-1; 1H nmr: ꢀ
1.01 (3H, d, J=6.9 Hz, CH3), 1.44 (9H, s, C(CH3)3), 2.55 (1H,
dqd, J=8.6, 6.9, 4.6 Hz, CH), 2.94 (1H, d, J=8.6 Hz, CH), 3.99
(1H, br s, NH), 5.58 (1H, d, J=4.6 Hz, CH), 7.09-7.36 and 7.83-
7.85 (9H, m, aromatic); ms: (CI) m/z 353 (MH+).
Anal. Calcd. for C23H28N2O: C, 79.27; H, 8.10; N, 8.04.
Found: C, 79.17; H, 8.16; N, 7.94.
2-t-Butylamino-3-(4-chlorophenyl)-6-methyl-4-phenyl-3,4-
dihydropyridine (9d).
Anal. Calcd. for C22H25ClN2: C, 74.88; H, 7.14; N, 7.94.
Found: C, 74.56; H, 7.03; N, 8.05.
This compound was obtained as colorless prisms, mp 96.0-
97.5˚; bp 176.0-179.0˚ (0.50 mmHg); ir: 3444, 1637, 1593,
1522, 1487, 1450 cm-1; 1H nmr: ꢀ 1.36 (9H, s, C(CH3)3), 1.99
3-(4-Bromophenyl)-2-t-butylamino-4-methyl-6-phenyl-3,4-
dihydropyridine (8e).

Sep-Oct 2006
Synthesis of Heterocyclic Compounds Using Amidines
1223
(3H, dd, J=1.4, 1.3 Hz, CH3), 3.17 (1H, d, J=5.7 Hz, CH), 3.35
(1H, ddq, J=5.7, 5.0, 1.4 Hz, CH), 3.88 (1H, br s, NH), 4.87 (1H,
dq, J=5.0, 1.3 Hz, CH), 7.08-7.26 (9H, m, aromatic); ms: (CI)
m/z 353 (MH+).
Anal. Calcd. for C22H25ClN2: C, 74.88; H, 7.14; N, 7.94.
Found: C, 75.01; H, 7.18; N, 7.83.
Anal. Calcd. for C28H30N2O: C, 81.91; H, 7.36; N, 6.82.
Found: C, 81.78; H, 7.56; N, 7.16.
2-t-Butylamino-3-(4-chlorophenyl)-4,6-diphenyl-3,4-dihydro-
pyridine (10d).
This compound was obtained as white prisms, mp 151.5-
152.0˚; ir: 3429, 1581, 1518, 1491, 1446 cm-1; 1H nmr: ꢀ 1.44
(9H, s, C(CH3)3), 3.29 (1H, d, J=4.6 Hz, CH), 3.58 (1H, dd,
J=5.7, 4.6 Hz, CH), 4.06 (1H, br s, NH), 5.70 (1H, d, J=5.7 Hz,
CH), 7.11-7.38 and 7.90-7.92 (14H, m, aromatic); ms: (CI) m/z
415 (MH+).
3-(4-Bromophenyl)-2-t-Butylamino-6-methyl-4-phenyl-3,4-
dihydropyridine (9e).
This compound was obtained as colorless prisms, mp 113.0-
114.5˚; bp 187.0-190.0˚ (0.40 mmHg); ir: 3440, 1637, 1593,
1522, 1483, 1450 cm-1; 1H nmr: ꢀ 1.36 (9H, s, C(CH3)3), 1.98
(3H, dd, J=1.4, 1.3 Hz, CH3), 3.15 (1H, d, J=5.4 Hz, CH), 3.34
(1H, ddq, J=5.4, 5.0, 1.4 Hz, CH), 3.88 (1H, br s, NH), 4.86 (1H,
dq, J=5.0, 1.3 Hz, CH), 7.03 and 7.40 (each 2H, d, J=8.6 Hz,
aromatic), 7.14-7.26 (5H, m, aromatic); ms: (CI) m/z 397 and
399 (MH+).
Anal. Calcd. for C27H27ClN2: C, 78.15; H, 6.56; N, 6.75.
Found: C, 78.15; H, 6.51; N, 6.81.
3-(4-Bromophenyl)-2-t-butylamino-4,6-diphenyl-3,4-dihydro-
pyridine (10e).
This compound was obtained as colorless prisms, mp 158.5-
160.0˚; ir: 3429, 1581, 1517, 1491, 1446 cm-1; 1H nmr: ꢀ 1.44
(9H, s, C(CH3)3), 3.27 (1H, d, J=4.6 Hz, CH), 3.57 (1H, dd,
J=5.7, 4.6 Hz, CH), 4.06 (1H, br s, NH), 5.70 (1H, d, J=5.7 Hz,
CH), 7.05-7.39 and 7.89-7.91 (14H, m, aromatic); ms: (CI) m/z
459 and 461 (MH+).
Anal. Calcd. for C22H25BrN2: C, 66.50; H, 6.34; N, 7.05.
Found: C, 66.24; H, 6.27; N, 6.99.
3,4-Dihydropyridines 10.
A solution containing N-t-butylacetamidines 1 (20.0 mmoles)
and chalcone (2 (R2=Ph, R3=Ph)) (20.0 mmoles) in diglyme (40
ml) was heated with stirring at 150˚ for the time indicated in
Table 2. After removal of the solvent under reduced pressure,
the residue was recrystallized from ethyl acetate to give 10. All
the products obtained were of satisfactory purity as judged by 1H
nmr spectroscopy. Analytical samples were prepared by further
recrystallization from ethyl acetate.
Anal. Calcd. for C27H27BrN2: C, 70.59; H, 5.92; N, 6.10.
Found: C, 70.93; H, 5.96; N, 6.18.
3,4-Dihydropyrrol-2-ones 13.
A solution containing N-t-butylacetamidines 1 (20.0 mmoles)
and ethyl 3-benzoylacrylate (12) (24.0 mmoles) in diglyme (40
ml) was heated with stirring at 120˚ for the time indicated in
Table 3. The reaction mixture was cooled, and the precipitated
product 13 was collected by filtration and washed with ethyl
acetate. Evaporation of combined filtrates under reduced
pressure and recrystallization of the residual solid from a small
amount of ethyl acetate, gave an additional amount of product
13. All the products obtained were of satisfactory purity as
judged by 1H nmr spectroscopy. Analytical samples were
prepared by further recrystallization from ethyl acetate.
2-t-Butylamino-3,4,6-triphenyl-3,4-dihydropyridine (10a).
This compound was obtained as a white powder, mp 123.5-
125.0˚; ir: 3425ꢀ1587ꢁ1510ꢁ1491ꢁ1450 cm-1; 1H nmr: ꢀ
1.44 (9H, s, C(CH3)3), 3.34 (1H, d, J=5.8 Hz, CH), 3.65 (1H, dd,
J=5.8, 5.4 Hz, CH), 4.10 (1H, br s, NH), 5.72 (1H, d, J=5.4 Hz,
CH), 7.18-7.39 and 7.91-7.93 (15H, m, aromatic); ms: (CI) m/z
381 (MH+).
5-t-Butylamino-3-(2-oxopropyl)-4-phenyl-3,4-dihydropyrrol-2-
one (13a).
Anal. Calcd. for C27H28N2: C, 85.22; H, 7.42; N, 7.36. Found:
C, 84.88; H, 7.59; N, 7.33.
This compound was obtained as a white powder, mp 232.5-
233.0˚; ir: 3296, 1712, 1678, 1572, 1545, 1450 cm-1; 1H nmr: ꢀ
1.42 (9H, s, C(CH3)3), 3.02 (1H, ddd, J=8.6, 5.1, 3.4 Hz, CH),
3.29 (1H, dd, J=17.6, 8.6 Hz, CH2), 3.68 (1H, dd, J=17.6, 3.4
Hz, CH2), 3.91 (1H, d, J=5.1 Hz, CH), 5.03 (1H, br s, NH), 7.12-
7.56 and 7.89-7.92 (10H, m, aromatic); ms: (CI) m/z 349
(MH+).
2-t-Butylamino-3-(4-methylphenyl)-4,6-diphenyl-3,4-dihydro-
pyridine (10b).
This compound was obtained as a white powder, mp 121.5-
123.0˚; ir: 3421, 1583, 1516, 1493, 1446 cm-1; 1H nmr: ꢀ 1.44
(9H, s, C(CH3)3), 2.29 (3H, s, CH3), 3.30 (1H, d, J=5.9 Hz, CH),
3.63 (1H, dd, J=5.9, 5.1 Hz, CH), 4.11 (1H, br s, NH), 5.71 (1H,
d, J=5.1 Hz, CH), 7.02-7.38 and 7.91-7.93 (14H, m, aromatic);
ms: (CI) m/z 395 (MH+).
Anal. Calcd. for C22H24N2O2: C, 75.83; H, 6.94; N, 8.04.
Found: C, 75.77; H, 7.03; N, 8.07.
Anal. Calcd. for C28H30N2: C, 85.24; H, 7.66; N, 7.10. Found:
C, 85.52; H, 7.75; N, 7.13.
X-Ray structure determinetion of compound 13a.
Crystal of 13a suitable for the structure analysis were
obtained by recrystallization from ethyl acetate.
2-t-Butylamino-3-(4-methoxyphenyl)-4,6-diphenyl-3,4-dihydro-
pyridine (10c).
The
measurements were made on a Rigaku RAXIS RAPID imaging
plate area detector with graphite monochromated Mo-Kꢁ
(ꢂ=0.71069 Å) radiation. The crystal structure was solved by
direct methods (SIR97) and expanded using Fourier techniques
(DIRDIF94)ꢂ(Figure 2).
Crystal data: Empirical formula C22H24N2O2; Formula weight
348.44; Crystal dimensions 0.20x0.10x0.10 mm; Crystal system
monoclinic; Lattice parameters a=13.6524(4) Å, b=8.3703(3) Å,
This compound was obtained as a pale yellow powder, mp
140.5-141.0˚; ir: 3421, 1610, 1587, 1512, 1491, 1444 cm-1; 1H
nmr: ꢀ 1.44 (9H, s, C(CH3)3), 3.30 (1H, d, J=6.3 Hz, CH), 3.62
(1H, dd, J=6.3, 5.1 Hz, CH), 3.76 (3H, s, CH3O), 4.12 (1H, br s,
NH), 5.73 (1H, d, J=5.1 Hz, CH), 6.80 and 7.10 (each 2H, d,
J=8.8 Hz, aromatic), 7.18-7.39 and 7.91-7.93 (10H, m,
aromatic); ms: (CI) m/z 411 (MH+).

1224
K. Ito, Y. Kizuka and S. Ihara
Vol 43
c=16.3741(6) Å, ꢀ=97.8278(8)˚, V=1853.7(1) Å3; Space group
Anal. Calcd. for C22H23ClN2O2: C, 69.01; H, 6.05; N, 7.32.
Found: C, 69.26; H, 6.12; N, 7.31.
P21/n (#14);
Z
value 4; Dcalc=1.248 g/cm3; F000=744.00;
μ(MoKꢁ)=0.80 cm-1; No. of reflections 21960; Residuals:
R1=0.043, R=0.074, wR=0.054; Goodness of fit indicator 1.11.
4-(4-Bromophenyl)-5-t-butylamino-3-(2-oxopropyl)-3,4-dihydro-
pyrrol-2-one (13e).
5-t-Butylamino-4-(4-methylphenyl)-3-(2-oxopropyl)-3,4-dihydro-
pyrrol-2-one (13b).
This compound was obtained as a white powder, mp 185.0-
187.0˚; ir: 3232, 1701, 1689, 1585, 1535, 1479, 1448 cm-1; 1H
nmr: ꢀ 1.43 (9H, s, C(CH3)3), 2.96 (1H, ddd, J=9.2, 4.9, 3.3 Hz,
CH), 3.24 (1H, dd, J=17.7, 9.2 Hz, CH2), 3.70 (1H, dd, J=17.7,
3.3 Hz, CH2), 3.85 (1H, d, J=4.9 Hz, CH), 5.04 (1H, br s, NH),
7.03 and 7.50 (each 2H, d, J=8.5 Hz, aromatic), 7.41-7.92 (5H,
m, aromatic); ms: (CI) m/z 427 and 429 (MH+).
This compound was obtained as a pale yellow powder, mp
212.0-213.0˚; ir: 3332, 1720, 1680, 1562, 1543, 1514, 1450
cm-1; 1H nmr: ꢂ 1.42 (9H, s, C(CH3)3), 2.34 (3H, s, CH3), 3.00
(1H, ddd, J=8.6, 5.2, 3.4 Hz, CH), 3.28 (1H, dd, J=17.7, 8.6 Hz,
CH2), 3.65 (1H, dd, J=17.7, 3.4 Hz, CH2), 3.87 (1H, d, J=5.2 Hz,
CH), 5.03 (1H, br s, NH), 7.01 and 7.16 (each 2H, d, J=8.0 Hz,
aromatic), 7.40-7.90 (5H, m, aromatic); ms: (CI) m/z 363
Anal. Calcd. for C22H23BrN2O2: C, 61.83; H, 5.42; N, 6.56.
Found: C, 61.88; H, 5.40; N, 6.53.
(MH+).
Acknowlegements.
Anal. Calcd. for C23H26N2O2: C, 76.21; H, 7.23; N, 7.73.
Found: C, 75.94; H, 7.41; N, 7.75.
The authors are grateful to the X-ray Research Laboratory,
Rigaku Corporation, for X-ray crystalꢀstructure data. Thꢁꢂ
study was supported as “High-Tech Research Center” Project
for Private Universities: matching fund subsidy from MEXT
(Ministry of Education Culture, Sports, science and
Technology), 2004-2008.
5-t-Butylamino-4-(4-methoxyphenyl)-3-(2-oxopropyl)-3,4-
dihydropyrrol-2-one (13c).
This compound was obtained as a pale yellow powder, mp
201.5-203.0˚; ir: 3334, 1720, 1678, 1562, 1541, 1512, 1448
cm-1; 1H nmr: ꢀ 1.42 (9H, s, C(CH3)3), 2.98 (1H, ddd, J=8.7, 5.1,
3.5 Hz, CH), 3.26 (1H, dd, J=17.5, 8.7 Hz, CH2), 3.67 (1H, dd,
J=17.5, 3.5 Hz, CH2), 3.81 (3H, s, CH3O), 3.85 (1H, d, J=5.1 Hz,
CH), 5.02 (1H, br s, NH), 6.88 and 7.04 (each 2H, d, J=8.7 Hz,
aromatic), 7.40-7.91 (5H, m, aromatic); ms: (CI) m/z 379
(MH+).
REFERENCES AND NOTES
[1] K. Ito, Y. Kizuka and Y. Hirano, J. Heterocyclic Chem., 42,
583 (2005).
[2] C. Kashima, M. Shimizu and Y. Omote, J. Heterocyclic
Chem., 26, 251 (1989).
[3a] A. L. Weis and D. Zamir, J. Org. Chem., 52, 3421 (1987);
[b] A. L. Weis, Synthesis, 528 (1985); [c] A. L. Weis and F. Frolow, J.
Org. Chem., 49, 3635 (1984).
ꢀ [4] A. L. Vais, V. M. Shyrina and V. P. Mamaev, Izv. Sib. Otd.
Akad. Nauk SSSR, Ser. Khim. Nauk, 1975, 144; Chem. Abstr., 84,
105528r (1976).
[5] M. Langlois, C. Guilloneau, T. Vo Van, R. Jolly and J.
Maillard, J. Heterocyclic Chem., 20, 393 (1983).
[6] J. C. Zhuo, molecules, 1999, 320.
[7] F. C. Cooper and M. W. Partridge, in Organic Syntheses,
Coll Vol 4, A. H. Blatt, ed, John Wiley & Sons, New York, NY, 1963, p
769.
Anal. Calcd. for C23H26N2O3: C, 72.99; H, 6.92; N, 7.40.
Found: C, 72.83; H, 6.91; N, 7.46.
5-t-Butylamino-4-(4-chlorophenyl)-3-(2-oxopropyl)-3,4-dihydro-
pyrrol-2-one (13d).
This compound was obtained as a pale yellow powder, mp
151.5-153.0˚; ir: 3327, 1722, 1672, 1562, 1547, 1491, 1450
cm-1; 1H nmr: ꢀ 1.43 (9H, s, C(CH3)3), 2.96 (1H, ddd, J=9.3, 4.9,
3.2 Hz, CH), 3.24 (1H, dd, J=17.6, 9.3 Hz, CH2), 3.71 (1H, dd,
J=17.6, 3.2 Hz, CH2), 3.86 (1H, d, J=4.9 Hz, CH), 5.03 (1H, br
s, NH), 7.09 and 7.35 (each 2H, d, J=8.3 Hz, aromatic), 7.41-
7.91 (5H, m, aromatic); ms: (CI) m/z 383 (MH+ ).