Synthesis and structure elucidation of 1-aryl-substituted tetrahydropyridone derivatives

Article abstract of DOI:10.1007/s10593-005-0216-2

A series of 1-aryl-1,4,5,6-tetrahydro-4(1H)-pyridones having substituents in 2,3- and 2,3,5-positions was prepared from N-aryl-β-alanines and ethyl acetoacetate or 2,4-pentanedione. Twelve tentative biologically active compounds were identified by the com

Full text of DOI:10.1007/s10593-005-0216-2

Chemistry of Heterocyclic Compounds, Vol. 41, No. 6, 2005
SYNTHESIS AND STRUCTURE
ELUCIDATION OF 1-ARYL-SUBSTITUTED
TETRAHYDROPYRIDONE DERIVATIVES
1
1
2
3
V. Mickevicius , R. Vaickelioniene , G. Mikulskiene , and N. Sewald
A series of 1-aryl-1,4,5,6-tetrahydro-4(1H)-pyridones having substituents in 2,3- and 2,3,5-positions
was prepared from N-aryl-β-alanines and ethyl acetoacetate or 2,4-pentanedione. Twelve tentative
1
13
1
13
biologically active compounds were identified by the combination of H, C and H/ C NMR
spectroscopy. The extensive interest has been focused on the influence of substituents as well as on the
number, attachment position, and the nature of the substituents. The unknown shielding of the
heterocyclic ring on the aromatic carbon atoms was determined and the averaged chemical shift
increments were successfully used for the assignment of the aromatic moiety of the studied compounds.
The presence of two chiral elements in compounds 16, 17, 20-21 resulted in the mixture of diastereomers
and double sets of the resonances in NMR spectra.
Keywords: N-aryl-β-alanines, tetrahydropyridones, NMR spectroscopy.
N-Aryl-β-alanines and their derivatives possess a wide spectrum of biological activity [1-3]. The
compounds under study are intermediate products in the synthesis of azetidinone, dihydroquinolone,
benzodiazepine, imidazole, and dihydropyrimidinedione derivatives [4-8].
In this paper we report a synthesis of 1-aryl-substituted tetrahydropyridones from N-aryl-β-alanines.
N-Aryl-β-alanines 1-12 were used as starting compounds. These compounds were obtained from the
corresponding arylamines and unsaturated acids by the method previously developed in our laboratory [5, 7].
1
-Aryl-3-ethoxycarbonyl-1,4,5,6-tetrahydro-4(1H)-pyridones 13-21 and 3-acetyl-1-aryl-1,4,5,6-
tetrahydro-4(1H)-pyridones 22-24 were prepared from the corresponding N-aryl-β-alanines and ethyl
acetoacetate or 2,4-pentanedione in refluxing toluene in the presence of a catalytic amount of hydrochloric acid.
It is possible that condensation of NH group in β-alanine with 1,3-diketo compound takes place first, and then
the intermediate compound undergoes cyclization resulting in the respective hydropyridone 13-24. The yield of
the target compounds was not high, however the formed products were crystalline substances and were obtained
from the reaction mixture easily.
The products obtained were analyzed by NMR spectroscopy. The NMR spectral assignments have been
made by the comparison of the spectra between themselves and with the related fragments, assuming the validity
of the additivity of the substituent effects, their general characteristics and the signal intensities [9-10].
_
_________________________________________________________________________________________
1
Kaunas University of Technology, Kaunas 50299, Lithuania; e-mail: Vytautas.Mickevicius@ktu.lt.
2
3
Institute of Biochemistry, Vilnius 08662, Lithuania. University of Bielefeld, PO Box 100131, 33501
Bielefeld, Germany. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 874-881, June 2005.
Original article submitted February 4, 2004.
7
54
0009-3122/05/4106-0754©2005 Springer Science+Business Media, Inc.

R 3
2
R 3
2
R
R
Me
R
MeCOCH COOEt
2
or MeCOCH COMe
3'
2'
2
3
2
4
4
R
R
NH
R1
N
O
1
'
4
4'
5' 6'
6
5
1
R 5
R 6
R 5
R 6
O
R
1
–12
13–24
1
2
3
5
6
4
1
-8, 13-20 R = COOEt, 9-12, 21-24 R = COMe; 1, 13 R = R = R = R = R = H, R = OMe;
1
3
5
6
2
4
1
3
5
2
4
6
2
, 14 R = R = R = R = H, R = R = Me; 3, 15 R = R = R = H, R = R = R = Me;
, 16 R = R = Me, R = R = R = R = H; 5, 17 R = R = R = Me, R = R = R = H;
, 18 R = R = R = Me, R = R = R = H; 7, 19 R = R = Me, R = R = R = R = H;
, 20 R = R = R = Me, R = R = R = H; 9, 21 R = R = R = Me, R = R = R = H;
1
2
3
4
5
6
1
2
3
4
5
6
4
6
8
1
3
5
2
4
6
1
4
2
3
5
6
1
2
4
3
5
6
1
2
5
3
4
6
1
2
3
5
6
4
1
3
4
5
6
2
1
0, 22 R = R = R = R = R = H, R = Br; 11, 23 R = R = R = R = R = H, R = Me;
1
3
4
6
2
5
1
, 24 R = R = R = R = H, R = R = Me
1
3
Examination of C NMR spectra was complicated due to the lack of published information about the
influence of the heterocyclic ring on the aromatic carbons. Therefore, this unknown influence was determined
1
3
during the present investigation. The C NMR spectra of compounds 13, 19, and 20 were potentially suitable for
detection of the desirable influence. It was derived from the spectral data of the aromatic moiety of these
compounds taking into account the influence of OMe, Me and Br as para-substituents on the aromatic carbon
atoms, signal intensities, and general features of the additivity effects of substituents. Averaged chemical shift
increments induced by the heterocyclic ring on the aromatic carbon atoms are shown in Table 1. The increments
obtained were further used successfully for the assignment of the resonances of the aromatic ring moiety of other
aryl-substituted compounds studied.
1
13
In the present work, H/ C 2D (HETCOR) NMR experiments [11, 12] were used to test, improve and
1
13
extend the H and C NMR assignments of the resonances of tetrahydropyridone derivatives under study. The
1
13
H/ C 2D NMR spectrum of compound 14 is presented in Fig. 1. The analysis was started from already known
assignments. The correlations of this experiment confirmed the 1D assignments and exhibited some
unexpectedness as well. Two of the cross-peaks of the methyl group resonances were pointed evidently to the
1
13
nonlinear relationship of the H and C NMR spectral data. The resonance of the more shielded methyl group
carbon atom located in C-2' position was correlated with the resonance of the more deshielded protons, although
the resonance of the more deshielded methyl group carbon atom in position C-2 coincided with the resonance of
the more shielded protons. The assignments of the corresponding resonances of other hydropyridone derivatives
were evaluated with no difficulty.
1
3
TABLE 1. C NMR Chemical Shift Increments (∆δ) Induced by the
Heterocyclic Group on the Aromatic Carbon Atoms
∆
δ, ppm
Compounds
C-i
C-o
C-m
C-p
1
1
2
3
9
2
15.90
17.16
16.17,
-1.61
-1.15
0.63
1.16
-1.45
-0.50
-1.12,
0.95,
-1.66,
1
6.21*
-1.03*
1.04*
-1.54*
Average values
16.36
-1.23
0.95
-1.29
_
*
______
1
3
The data from C NMR spectra, obtained using Bruker DRX 500
spectrometer operating at 125 MHz.
7
55

Fig. 1. HETCOR spectrum of compound 14 by Bruker DRX 500, at 500.130 MHz in CDCl3.
1
3
1
All resonances of the compounds studied have been assigned unambiguously. The C and H NMR
spectral data for the compounds 13-24 under study are presented in Tables 2-4.
The resonances of the heterocyclic ring moiety carbon atoms revealed the characteristic effects due to
the influence of the present substituents. The resonances of C-2 atoms in compounds 22-24 were shifted
downfield by 4.5 ppm in respect to those in 13-21, while their chemical shifts predicted by the additivity rule
showed the opposite trend. The signals of C-3 atoms in both groups of compounds were found to resonate
according to the usual substituent effects.
The methyl group attached to position-5 in compounds 16-21 caused about 3-4 ppm downfield shift for
the C-4 atoms, while the β-influence of methyl group on the C-6 atoms reached about 6 ppm. It was interesting
to notice that the chiral centre at C-5 arose due to the methyl group in the compounds mentioned above,
1
consequently the ABX spin system of hydrogens attached to C-6 and C-5 atoms, was present in H NMR
1
spectra. H NMR studies of the tentative hydropyridones provided a part of the reliable and necessary
information on their structures.
On the other hand, the methyl substituents attached to the benzene ring afforded valuable information
about structural features of the molecules of the studied compounds. Compounds 16, 17, 20, 21 possessing the
asymmetrical axis due to the asymmetrical substituted benzene ring existed as diastereoisomers [13] and were
detected as two separate isomers in their NMR spectra. Two sets of the resonances were observed in the NMR
1
spectra of the compounds mentioned above. The intensities of the pairs of resonances measured from H spectra
showed the ratio of 4:6.
Analysis of NMR spectra showed that there were no double sets of the resonances in compounds 14, 23,
2
4, which possess asymmetrical substituted benzene ring but have no 5-methyl substituent in heterocycle ring.
Similar effect was observed for compounds 16, 17, which possess 5-methyl substituent in the heterocycle ring,
but have symmetrically substituted benzene ring. Moreover, compounds 13, 15, 20, owing to the presence of the
symmetrically substituted benzene ring and absence of the 5-methyl substituent in the heterocycle ring, had no
double resonances.
7
56

1
3
TABLE 2. C NMR Spectral Data of Compounds 13-18
Chemical shifts, δ, ppm
Carbon
1
3
14
15
16
17
18
C-2
C-3
C-4
C-5
C-6
C-1'
C-2'
C-3'
C-4'
C-5'
C-6'
161.83
106.74
186.55
35.43
162.38
162.46
161.51,
163.61,
163.47
162.54
1
61.28
105.44,
05.37
189.46,
89.25
37.79,
7.63
55.99,
5.68
142.38,
42.27
134.98,
34.74
131.32,
31.25
128.55,
28.46
127.51,
27.44
127.90,
27.18
18.65,18.60,
106.10
186.55
35.43
105.52
186.26
35.34
106.02
106.70
190.52
38.75
1
190.36,
190.25
1
38.49,
38.40
3
51.35
50.08
48.48
57.28,
57.08
58.06
5
136.69
127.93
114.71
158.45
114.71
127.93
19.20
140.03
138.02
131.82
134.49
128.02
127.21
18.81
138.68
134.69
129.44
137.73
129.44
134.69
17.95
142.81,
142.75
144.05
124.11
139.87
129.75
139.87
124.11
1
133.7,
133.64
1
139.25,
139.20
1
130.17,
130.11
1
127.08,
127.00
1
125.15,
124.44
1
2
-CH
3
19.33,
19.17
1
8.50,18.45
COOCH
2
CH
3
167.16;
167.16;
59.52;
14.18
167.02;
59.40;
14.12
167.25;
59.49,58.47;
14.12,14.08
168.03,
167.99;
60.49;
168.06;
60.16;
14.63
5
9.48;
4.10
1
1
4.41
5
2
3
-CH
3
13.05,12.99,
12.88,
13.19
14.21,
14.25
12.99
1
2.36,12.31
17.24,17.21,
7.13,17.17
'-CH
'-CH
3
3
17.13
20.57
17.30
1
20.48,
21.20
21.20
2
0.36
4
5
'-CH
'-CH
3
(OCH
3
)
55.35
20.41
17.30
3
6
'-CH
3
More detailed investigations of the structural features of studied compounds 13-24 were carried out by
the combination of NMR spectral and computer molecular modeling data analysis. Molecular modeling was
based on CS MM2 5.0 and CS MOPAC 5.0 by using molecular mechanics and semiempirical quantum-
mechanical methods, respectively. The geometry of the molecules of the compounds under studies was
optimized to the global minimum of steric energy summary. Molecular modeling analysis showed that the
sterical arrangement of the optimized molecular models changed due to the different methylsubstitution of both
rings of molecules of the compounds under studies. Investigations on rotation of benzene and heterocycle rings
around the (C-1')–(N-1) bond showed significant energetic barriers. The largest value of the hindered rotation
barrier was estimated for compounds 16, 17, 20, 21.
7
57

1
3
TABLE 3. C NMR Spectral Data of Compounds 19-24
Chemical shifts, δ, ppm
Carbon
1
9
20
21
22
23
24
C-2
161.16
162.06,
162.64,
162.41
165.69
166.96
167.24
1
61.85
C-3
C-4
108.05
189.88
105.70
189.75,
106.40
114.00
189.29
113.01
189.11
112.93
189.09
190.54,
190.35
1
89.57
38.56,
8.14
56.45,
6.14
140.27,
40.17
138.29,
38.20
C-5
C-6
C-1'
C-2'
C-3'
C-4'
C-5'
C-6'
39.42
58.69
38.75,
38.59
35.73
51.05
35.75
49.88
35.75
49.94
3
57.02,
56.70
5
142.86
127.35
130.96
138.30
130.96
127.35
19.24
143.28,
143.17
143.09
128.98
132.65
121.04
132.65
128.98
20.12
142.51
134.37
131.34
128.72
127.04
127.56
19.71
140.04
133.92
131.80
128.04
138.17
126.72
19.73
1
132.62,
132.41
1
132.07
132.14,
1
32.08
134.90,
130.23,
130.24
1
34.66
128.37,
28.28
127.94,
27.22
18.96,
8.81
138.03,
137.97
1
129.23,
128.47
19.54,
19.39
1
2
-CH
3
1
COOCH
2
CH
3
168.11;
167.63;
59.80;
14.47
168.36;
60.42;
5.03
6
0.16;
4.63
1
COCH
3
198.52;
197.89;
32.33
197.94;
32.32
3
2.33
5
2
4
5
-CH
3
13.87,
1
3.29
'-CH
'-CH
'-CH
3
3
3
13.39,
17.70,
17.59
17.06
16.98
20.48
1
2.75
17.50,
7.38
20.96
1
21.16
1
TABLE 4. H NMR Spectra of Compounds 13-24
Com-
pound
Chemical shifts, δ, ppm (coupling constants, J, Hz)
1
2
1
1
1
1
1
3
4
5
6
7
1.20 (3H, t, J = 7.1, COOCH
2
CH
3
); 1.85 (3H, s, 2-CH
3
); 2.42-2.53 (2H, m, COCH
2
);
3
6
.80 (3H, s, OCH
.95-7.35 (4H, m, Ar)
3
); 3.71-3.86 (2H, m, NCH
2
); 4.15 (2H, q, J = 7.1, COOCH
2
CH );
3
1.15 (3H, t, J = 7.1, COOCH
2
CH
); 2.36-2.58 (2H, m, COCH
.08 (2H, q, J = 7.1, COOCH CH ); 7.08-7.20 (3H, m, Ar)
CH ); 1.75 (3H, s, 2-CH ); 2.18 (6H, s, 2',6'-CH
); 2.44-2.53 (2H, m, COCH ); 3.60-3.75 (2H, m, NCH );
.10 (2H, q, J = 7.1, COOCH CH ); 7.00 (2H, s, Ar-3', 5')
); 1.15 (3H, t, J = 7.1, COOCH
); 2.23, 2.28 (3H, 2s, 2'-CH ); 2.55-2.67 (1H, m, COCH);
.50-3.72 (2H, m, NCH ); 4.06 (2H, q, J = 7.1, COOCH CH ); 7.26-7.46 (4H, m, Ar)
); 1.39 (3H, t, J = 7.1, COOCH CH ); 1.96 and 1.98 (3H, 2s,
); 2.19 and 2.25 (3H, 2s, 2'-CH ); 2.33 and 2.34 (3H, 2s, 3'-CH );
.60-2.82 (1H, m, COCH); 3.42-3.70 (2H, m, CH N); 4.30 (2H, q, J = 7.1,
CH ); 6.90-7.30 (3H, m, Ar)
3
); 1.75 (3H, s, 2-CH
3
); 2.18 (3H, s, 2'-CH
3
);
2
4
.27 (3H, s, 4'-CH
3
2
); 3.58-3.80 (2H, m, NCH
2
);
2
3
1.20 (3H, t, J = 7.1, COOCH
2
4
2
3
3
3
);
.25 (3H, s, 4'-CH
3
2
2
2
3
1.00, 1.04 (3H, 2d, J = 6.8, 5-CH
1
3
3
2 3
CH );
.74 (3H, s, 2-CH
3
3
2
2
3
1.24 (3H, d, J = 6.8, 5-CH
2
2
3
2
3
-CH
3
3
3
2
COOCH
2
3
7
58

TABLE 4 (continued)
1
2
1
1
2
8
9
0
1.18 (3H, d, J = 6.9, 5-CH
3
2 3
); 1.34 (3H, t, J = 7.1, COOCH CH ); 2.00 (3H, s,
2
-CH
.28 (2H, q, J = 7.1, COOCH
); 1.15 (3H, t, J = 7.1, COOCH
); 2.40-2.80 (1H, m, COCH); 3.56-4.00 (2H, m, NCH
CH ); 7.21-7.53 (4H, m, Ar)
1.02 and 1.05 (3H, 2d, J = 6.9, 5-CH ); 1.18 (3H, t, J = 7.1, COOCH
); 2.19-2.24 (3H, 2s, 2'-CH ); 2.32 (3H, s, 4'-CH
.49-2.70 (1H, m, COCH); 3.40-3.70 (2H, m, NCH ); 4.09 (2H, q, J = 7.1,
CH ); 7.10-7.30 (3H, m, Ar)
0.99 and 1.03 (3H, 2d, J = 6.9, 5-CH ); 1.18 (3H, t, J = 7.1, COOCH
); 2.14 and 2.19 (3H, 2s, 2'-CH );
.47 and 2.49 (3H, 2s, 5'-CH );
.45-2.53 (1H, m, COCH); 3.40-3.75 (2H, m, NCH
CH ); 7.00-7.30 (3H, m, Ar)
1.95 (3H, s, 2-CH ); 2.35 (3H, s, COCH
.82-3.93 (2H, m, NCH ); 7.35-7.80 (4H, m, Ar)
); 2.25 (3H, s, 2'-CH ); 2.35 (3H, s, COCH
); 7.28-7.47 (4H, m, Ar)
); 2.25 (3H, s, 2'-CH ); 2.27 (3H, s, 5'-CH
.40-2.68 (2H, m, COCH ); 3.61-3.86 (2H, m, NCH ); 7.08-7.22 (3H, m, Ar)
3
); 2.34 (6H, s, 3',5'-Ar); 2.53-2.72 (1H, m, COCH); 3.53-3.83 (3H, m, NCH
CH ); 6.77 (2H, s, 2',6'-CHAr); 6.99 (H, s, 4'-CHAr)
CH ); 1.74 (3H, s, 2-CH
); 4.06 (2H, q,
2
);
4
2
3
1.02 (3H, d, J = 6.9, 5-CH
.23 (3H, s, 4'-CH
J = 7.1, COOCH
3
2
3
3
);
2
3
2
2
3
3
2 3
CH );
1
2
.76 and 1.77 (3H, 2s, 2-CH
3
3
3
);
2
COOCH
2
3
2
1
3
2 3
CH );
1
2
2
.74 and 1.75 (3H, 2s, 2-CH
3
3
3
2
); 4.06 (2H, q, J = 7.1,
);
); 2.45- 2.73 (2H, m,
3
); 2.35 (3H, s, COCH );
COOCH
2
3
2
2
2
2
3
4
3
3 2
); 2.50-2.65 (2H, m, COCH
3
2
1.90 (3H, s, 2-CH
3
3
3
2 2
COCH ); 3.66-3.90 (2H, m, NCH
1.90 (3H, s, 2-CH
3
3
3
2
2
2
EXPERIMENTAL
1
13
The H and C NMR spectra were recorded as solutions of 50 mg of each compound in 0.7 ml of
DMSO-d (13-16, 20-24), CDCl (17, 18), acetone-d (19). Chemical shifts are reported as δ (ppm) downfield
6
3
6
1
3
from TMS. Samples were spun in 5 mm o.d. tubes at ambient temperature. C NMR spectra were obtained at
5
0 MHz on a Varian Gemini-200 spectrometer and at 63 MHz on AC 250-P Bruker spectrometer operating in
1
13
Fourier transform mode. H/ C 2D spectra were recorded on a Bruker DRX 500 spectrometer operating at
5
1
13
00 MHz ( H) and 125 MHz ( C), using standard software for data acquisition, processing and plotting.
Preparation of 1-Aryl-3-ethoxycarbonyl-1,4,5,6-tetrahydro-4(1H)-pyridones 13-21 and 3-Acetyl-1-
aryl-1,4,5,6-tetrahydro-4(1H)-pyridones 22-24. To a mixture of corresponding N-aryl-β-alanine 1-12
(
0.1 mol) and ethyl acetoacetate (or 2,4-pentanedione) (40 ml) in toluene (50 ml), concentrated hydrochloric acid
(
5 ml) were added and the mixture was heated under reflux for 15 h removing liberated water by Dean–Stark
trap. The solvents were removed in vacuo, the residue suspended in 5 % Na CO (150 ml) and extracted with
2
3
diethyl ether (4 × 100 ml). The solvent was removed in vacuo, the oil was recrystallized from corresponding
solvent to afford a white solid, or separated by flash chromatography.
3
-Ethoxycarbonyl-1-(4-methoxyphenyl)-2-methyl-1,4,5,6-tetrahydro-4(1H)-pyridone
(13):
mp 145-146°C (hexane), yield 11.5%. Found, %: C 66.71; H 6.43; N 4.69. C H NO . Calculated, %: C 66.42;
1
6
19
4
H 6.62; N 4.84.
-(2,4-Dimethylphenyl)-3-ethoxycarbonyl-2-methyl-1,4,5,6-tetrahydro-4(1H)-pyridone
mp 122-123°C (hexane), yield 12.3%. Found, %: C 71.21; H 7.15; N 4.64. C H NO . Calculated, %: C 71.06;
1
(14):
1
7
21
3
H 7.37; N 4.87.
3
-Ethoxycarbonyl-2-methyl-1-(2,4,6-trimethylphenyl)-1,4,5,6-tetrahydro-4(1H)-pyridone (15):
mp 95-97°C, yield 4.5% after purification by column chromatography (diethyl ether). Merk Kieselgel l60 silica
gel (15-40 µm) was used for column chromatography. Found, %: C 71.56; H 7.78; N 4.46. C H NO .
1
8
23
3
Calculated, %: C 71.73; H 7.69; N 4.65.
-Ethoxycarbonyl-2,5-dimethyl-1-(2-methylphenyl)-1,4,5,6-tetrahydro-4(1H)-pyridone
mp 90-91°C (heptane), yield 10.7%. Found, %: C 71.35; H 7.80; N 4.75. C H NO . Calculated, %: C 71.06;
3
(16):
1
7
21
3
H 7.37; N 4.87.
7
59

1
-(2,3-Dimethylphenyl)-3-ethoxycarbonyl-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)-pyridone (17):
3
mp 109-110°C (ethanol), yield 17.7%. Found, %: C 71.55; H 7.42; N 4.41. C18H23NO . Calculated, %: C 71.73;
H 7.69; N 4.65.
1
-(3,5-Dimethylphenyl)-3-ethoxycarbonyl-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)-pyridone (18):
mp 111-112°C (ethanol), yield 6.6%. Found, %: C 71.46; H 7.82; N 4.47. C H NO . Calculated, %: C 71.73;
1
8
23
3
H 7.69; N 4.65.
-Ethoxycarbonyl-2,5-dimethyl-1-(4-methylphenyl)-1,4,5,6-tetrahydro-4(1H)-pyridone
mp 80-82°C (hexane), yield 27.7%. Found, %: C 71.53; H 7.85; N 4.55. C H NO . Calculated, %: C 71.06;
3
(19):
1
7
21
3
H 7.37; N 4.87.
-(2,4-Dimethylphenyl)-3-ethoxycarbonyl-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)-pyridone (20):
mp 102-103°C (heptane), yield 14.7%. Found, %: C 71.55; H 7.42; N 4.46. C H NO . Calculated, %: C 71.73;
1
1
8
23
3
H 7.69; N 4.65.
-(2,5-Dimethylphenyl)-3-ethoxycarbonyl-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)-pyridone (21):
mp 89-90°C (heptane), yield 14.7%. Found, %: C 71.46; H 7.21; N 4.51. C H NO . Calculated, %: C 71.73;
1
1
8
23
3
H 7.69; N 4.65.
-Acetyl-1-(4-bromophenyl)-2-methyl-1,4,5,6-tetrahydro-4(1H)-pyridone (22): mp 73-75°C
ethanol), yield 18.7%. Found, %: C 54.33; H 4.36; N 4.78. C H BrNO . Calculated, %: C 54.56; H 4.58;
3
(
1
4
14
2
N 4.55.
3
-Acetyl-2-methyl-1-(2-methylphenyl)-1,4,5,6-tetrahydro-4(1H)-pyridone (23): mp 49-51°C
(
(
heptane), yield 54.9%. Found, %: C 74.32; H 6.89; N 5.87. C H NO . Calculated, %: C 74.05; H 7.04; N 5.76.
1
5
17
2
3
-Acetyl-2-methyl-1-(2,5-dimethylphenyl)-1,4,5,6-tetrahydro-4(1H)-pyridone (24): mp 67-68°C
heptane), yield 26.2%. Found, %: C 74.49; H 7.71; N 5.27. C H NO . Calculated, %: C 74.68; H 7.44; N 5.44.
1
6
19
2
REFERENCES
1
.
H. Narita, Y. Konishi, J. Nitta, Sh. Misumi, H. Nagaki, I. Kitayama, Y. Nagai, and Y. Watanabe,
DE Patent, Offen DE 3338846 (1984); Chem. Abstr., 101, 171101 (1984).
2
3
4
5
6
7
.
.
.
.
.
.
T. Hudson, GB Patent, GB 2238788 (1991); Chem. Abstr., 115, 183118 (1991).
Z. F. Solomko, A. N. Kost, L. N. Polovina, and M. A. Salimov, Khim. Geterotsikl. Soed., 987 (1971).
S. Kano, T. Ebata, and S. Shibuya, J. Chem. Soc., Perkin Trans. 1, 1105 (1980).
V. Mickevicius, Khim. Geterotsikl. Soed., 523 (1996).
D. Aelony and W. J. McKillip, J. Heterocycl. Chem., 9, 687 (1972).
V. Mickevicius, R. Baltrusis, J. Bylinskaite, E. Liepins, and R. Zolotojabko, Khim. Geterotsikl. Soed.,
1
240 (1991).
8
9
.
.
V. Mickevicius and J. Bylinskaite, Chemistry (Vilnius), No. 2, 86 (1997).
H. O. Kalinowski, S. Berger, and S. Braun, C NMR-Spektroskopie, Georg Thieme Verlag, Stuttgart,
New York, 1984.
1
3
1
1
1
1
0.
1.
2.
3.
E. Pretsch, T. Clerc, J. Seibl, and W. Simon, Tables of Spectral Data for Structure Determination of
Organic Compounds, Springer-Verlag, New York, 1989.
H. Friebolin, Basic One- and Two-Dimensional NMR Spectroscopy, VCH Verlags-Gesellshaft,
Weinheim and VCH Publishers, New York, 1991.
H. Duddeck, W. Dietrich, and G. Toth, Structure Elucidation by Modern NMR, Springer, Darmstadt,
Steinkopff, New York, 1998.
M. Nogradi, Stereokhimiya, Mir, Moscow, 1984.
7
60