Synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)- diones

Article abstract of DOI:10.1007/s11172-008-0066-z

An efficient method for the synthesis of novel 3-(1,3-thiazol-2-yl)-7,8- dihydroquinoline-2,5(1H,6H)-diones from various 2- dimethylaminomethylidenecyclohexane-1,3-diones, (1,3-thiazol-2-yl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These transformations proceeded through intermediate 2-[2-(4-aryl-1,3-thiazol-2-yl)-2-cyanoethenyl]-3- oxocyclohex-1-en-1-olates. They were isolated as piperidinium salts and used in further heterocyclization reactions with aromatic amines, giving novel 1-aryl-3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones. These compounds were also obtained by preparative three-step "one pot" synthesis under controlled microwave irradiation.

Full text of DOI:10.1007/s11172-008-0066-z

Russian Chemical Bulletin, International Edition, Vol. 57, No. 2, pp. 422—427, February, 2008
422
Synthesis of novel 3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ
7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdiones
S. G. Dzhavakhishvili, N. Yu. Gorobets,ꢀ V. N. Chernenko, V. I. Musatov, and S. M. Desenko
Scientific and Technological Corporation “Institute for Single Crystals”,
National Academy of Sciences of Ukraine,
60 prosp. Lenina, 61001 Kharkov, Ukraine.
Fax: +7 (057) 340 9343. Eꢀmail: gorobets@isc.kharkov.com
An efficient method for the synthesis of novel 3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ
2,5(1H,6H)ꢀdiones from various 2ꢀdimethylaminomethylidenecyclohexaneꢀ1,3ꢀdiones,
(1,3ꢀthiazolꢀ2ꢀyl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These
transformations proceeded through intermediate 2ꢀ[2ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ2ꢀyl)ꢀ2ꢀcyanoethenyl]ꢀ
3ꢀoxocyclohexꢀ1ꢀenꢀ1ꢀolates. They were isolated as piperidinium salts and used in further
heterocyclization reactions with aromatic amines, giving novel 1ꢀarylꢀ3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ
7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdiones. These compounds were also obtained by preparaꢀ
tive threeꢀstep “one pot” synthesis under controlled microwave irradiation.
Key words: 3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdiones, cyclization,
2ꢀ[2ꢀcyanoꢀ2ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ethenyl]ꢀ3ꢀoxocyclohexꢀ1ꢀenolates, aromatic amines, microꢀ
wave irradiation, nuclear Overhauser effect.
Scheme 1
An important problem that organic chemists are faced
with today is development of methods for the synthesis of
compounds with desired properties and creation of comꢀ
binatorial libraries of compounds with potential biologiꢀ
cal activity. Some 3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)pyridinꢀ2(1H)ꢀones
have been found to act as selective GABAA antagonists1
and anxiolytics.2—4 That is the reason why the synthesis of
novel derivatives combining 2ꢀpyridone and 1,3ꢀthiazole
fragments is of current interest.
Results and Discussion
One of the methods of constructing the pyridinꢀ2(1H)ꢀ
one ring involves reactive enamines prepared by condenꢀ
sation of various dicarbonyl compounds with dimethylꢀ
formamide dimethyl acetal (DMFDMA). We used
(Scheme 1) 2ꢀdimethylaminomethylidenecyclohexaneꢀ
1,3ꢀdiones 2a—d (prepared from cyclohexaneꢀ1,3ꢀdiones
1a—d and DMFDMA) as starting materials for our present
work. Their structure allows variation of the substituent in
the dicarbonyl component, and the dimethylaminomethylidene
fragment may be involved in reactions with various active
methylene nitriles to form the pyridone ring5.
Here we studied transformations of some cyclohexꢀ
aneꢀ1,3ꢀdiones 1a—d in reactions with (1,3ꢀthiazolꢀ
2ꢀyl)acetonitriles 3a—e.
Reactions of 2ꢀdimethylaminomethylidenecycloꢀ
hexaneꢀ1,3ꢀdiones5 2a—d with nitriles 3a—d in boiling
1, 2: R1 = R2 = H (a); R1 = R2 = Me (b);
R
1 = H, R2 = 4ꢀMeOC6H4 (c); R1 = H, R2 = 2ꢀfuryl (d)
BunOH (method A) in the presence of catalytic amounts
of piperidine for 10 min yielded 3ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ
2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdiones 4 in the
individual state (Scheme 2; Tables 1, 2). A previously
described microwaveꢀassisted method6 for the synthesis
of various pyridinꢀ2(1H)ꢀones5 is also applicable for the
preparation of these compounds. For instance, irradiaꢀ
tion of the reaction mixture in PriOH at 100 °C for 5 min
(method B) also gave the target products 4 (see Scheme 2).
Their yields were slightly higher (see Table 1) and no
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412—417, February, 2008.
1066ꢀ5285/08/5702ꢀ0422 © 2008 Springer Science+Business Media, Inc.

3ꢀ(1,3ꢀThiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolinediones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 2, February, 2008
423
Scheme 2
Reagents and conditions: i. BunOH, piperidine, reflux, 10 min (method A). ii. PriOH, piperidine, microwave irradiation, 100 °C, 5 min
(method B). iii. PriOH, piperidine, 20 °C. iv. AcOH, reflux.
3
a
b
c
d
R3
R4
H
H
H
Me
4
a
b
c
d
R1
H
Me
H
R2
H
Me
R3
R4
H
H
Me
H
5
a
b
R1
Me
H
R2
Me
R3
4ꢀClC6H4
R4
H
H
4ꢀClC6H4
3ꢀNO2C6H4
4ꢀEtOC6H4
4ꢀMeC6H4
3ꢀNO2C6H4
4ꢀEtOC6H4
4ꢀMeOC6H4 3ꢀNO2C6H4
4ꢀMeOC6H4 4ꢀMeC6H4
2ꢀFuryl 4ꢀClC6H4
H
Table 1. Selected physicochemical characteristics of compounds 4, 5, and 7
Comꢀ
pound
M.p
/°С
Yield*
(%)
Found
Calculated
Molecular
formula
(%)
N
А
B
C
H
S
4a
4b
4c
4d
5a
5b
7a
7b
7c
7d
7e
298—301
285—288
283—285
294—296
278—280
291—292
307—309
297—300
283—285
250—251
284—286
52
61
58.79
58.85
66.66
66.98
71.41
71.03
62.55
62.49
64.22
64.02
64.34
64.62
61.91
61.79
68.22
68.27
71.10
71.16
64.75
64.86
70.06
70.27
3.68
11.69
11.44
7.31
7.10
6.42
6.14
6.81
6.62
9.02
8.96
10.33
10.05
5.60
5.54
6.04
5.90
6.06
5.93
6.13
6.05
4.98
4.82
8.83
8.73
7.61
8.13
6.59
7.02
7.49
7.58
6.81
6.84
5.52
5.75
6.14
6.34
6.55
6.75
6.19
6.78
6.77
6.93
5.48
5.52
C18H13N3O4S
3.57
5.64
5.62
5.40
5.30
3.62
3.58
5.75
5.80
5.30
5.24
4.18
4.19
4.92
4.88
5.44
5.33
4.21
4.14
5.06
5.03
51
55
50
63
68
55
C22H22N2O3S
C27H24N2O3S
C22H15ClN2O3S
C25H28ClN3O2S
C30H30N4O5S
78
73
—
57
—
48
55
76
79
74
69
73
C26H21BrN2O2S
C27H23ClN2O2S
C28H25FN2O2S
C25H19ClN2O3S
C34H29ClN2O3S
* With respect to cyclohexaneꢀ1,3ꢀdione derivatives.

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Dzhavakhishvili et al.
Table 2. IR and 1H NMR spectra of compounds 4, 5, and 7
Comꢀ
pound
IR,
ν/cm–1
1H NMR,
δ (J/Hz)
4a
4b
4c
4d
5a
5b
3359 (N—H); 2852 (С(sp3)—H); 1.96—2.18 (m, 2 H); 2.52, 2.91 (both t, 2 H each, J = 5.9); 7.75 (t, 1 H, H(5)Ar(2)
,
1647 (C=O); 1528 (asꢀNO2);
1347 (sꢀNO2)
J = 8.2); 8.20 (d, 1 H, H(4)Ar(2), J = 8.2); 8.35—8.56 (m, 2 H, H arom.);
8.80 (s, 1 H); 8.89 (s, 1 H, H(4)); 12.83 (s, 1 H, NH)
3342 (N—H); 2968 (С(sp3)—H); 1.03 (s, 6 H, 2 Me); 1.33 (t, 3 H, CH3CH2, J = 7.0); 2.42, 2.80 (both s, 2 H each);
1647 (C=O); 1244 (CAr—O—C)
4.05 (q, 2 H, CH3CH2, J = 7.0); 6.99 (d, 2 H, H(3)Ar(2), H(5)Ar(2), J = 8.9);
7.81—8.02 (m, 3 H); 8.86 (s, 1 H, H(4)); 12.83 (s, 1 H, NH)
3418 (N—H); 2919 (С(sp3)—H); 2.35, 2.56 (both s, 3 H each, Me); 2.61—2.69 (m, 1 H); 2.76—3.18 (m, 3 H); 3.40—3.54
1650 (C=O); 1514 (C=N)
(m, 1 H); 3.72 (s, 3 H, MeO); 6.90 (d, 2 H, HAr(1), J = 8.5); 7.12—7.41 (m, 4 H,
H arom.); 7.63 (d, 2 H, HAr(2), J = 7.9); 8.79 (s, 1 H, H(4)); 12.87 (s, 1 H, NH)
3401 (N—H); 2929 (С(sp3)—H); 2.71—2.92, 3.02—3.25 (both m, 2 H each); 3.61—3.80 (m, 1 H); 6.18 (d, 1 H,
1643 (C=O); 748 (C—Cl)
J = 2.9); 6.38 (s, 1 H); 7.39—7.69 (m, 3 H, H arom.); 8.07 (d, 2 H, H arom.,
J = 8.4); 8.20 (s, 1 H, HTz); 8.88 (s, 1 H, H(4)); 12.97 (s, 1 H, NH)
2955 (С(sp3)—H); 2200 (CN);
1546 (C=O); 1505 (C=N)
0.94 (s, 6 H, 2 Me); 1.32—1.82 (m, 7 H); 2.10—2.18 (m, 3 H); 2.86—3.04 (m, 4 H);
7.47 (d, 2 H, H(3)Ar(2), H(5)Ar(2), J = 8.7); 7.80 (s, 1 H); 7.95 (d, 2 H, H(2)Ar(2)
H(6)Ar(2), J = 8.7); 8.13 (s, 1 H)
,
2956 (С(sp3)—H); 2220 (CN);
1551 (С=О); 1534 (asꢀNO2);
1374 (sꢀNO2)
1.30—1.80 (m, 6 H); 2.32—2.45, 2.49—2.65 (both m, 2 H each); 2.88—3.08 (m, 4 H);
3.10—3.24 (m, 1 H); 3.71 (s, 3 H, MeO); 6.84 (d, 2 H, H(3)Ar(1), H(5)Ar(1), J = 8.6);
7.22 (d, 2 H, H(2)Ar(1), H(6)Ar(1), J = 8.6); 7.73 (t, 1 H, H(5)Ar(2), J = 8.1);
8.00—8.28 (m, 3 H, H arom.); 8.38 (d, 1 H, H(6)Ar(2), J = 8.1); 8.74 (s, 1 H)
7a
7b
2956 (С(sp3)—H); 1663 (C=O);
1540 (C=N); 1229 (CAr—N)
0.96 (s, 6 H, 2 Me); 2.32—2.45 (m, 4 H); 7.44 (d, 2 H, HAr(3), J = 7.3);
7.51—7.76 (m, 5 H, H arom.); 8.03 (d, 2 H, H(2)Ar(2), H(6)Ar(2), J = 8.2);
8.24 (s, 1 H, HTz); 9.06 (s, 1 H, H(4))
2956 (С(sp3)—H); 1657 (C=O);
1541 (C=N); 1224 (CAr—N);
758 (C—Cl)
0.94 (s, 6 H, 2 Me); 2.41 (s, 4 H); 2.47 (s, 3 H, Me); 7.28 (d, 2 H, H(3)Ar(3),
H(5)Ar(3), J = 8.3); 7.41 (d, 2 H, H(2)Ar(3), H(6)Ar(3), J = 8.3); 7.52 (d, 2 H,
H(3)Ar(2), H(5)Ar(2), J = 8.6); 8.07 (d, 2 H, H(2)Ar(2), H(6)Ar(2), J = 8.6);
8.20 (s, 1 H, HTz); 9.04 (s, 1 H, H(4))
7c
7d
2955 (С(sp3)—H); 1664 (C=O);
1544 (C=N); 1232 (CAr—N)
0.95 (s, 6 H, 2 Me); 2.35 (s, 3 H, Me); 2.42 (s, 4 H); 2.54 (s, 3 H, Me);
7.29 (d, 2 H, H(3)Ar(2), H(5)Ar(2), J = 8.2); 7.38—7.58 (m, 4 H, H arom.);
7.64 (d, 2 H, H(2)Ar(2), H(6)Ar(2), J = 8.2); 8.92 (s, 1 H, H(4))
2853 (С(sp3)—H); 1654 (C=O);
1540 (C=N); 1274 (CAr—N);
774 (C—Cl)
1.90—2.11 (m, 2 H); 2.49—2.67 (m, 4 H); 3.83 (s, 3 H, MeO); 7.12 (d, 2 H,
H(3)Ar(3), H(5)Ar(3), J = 8.9); 7.35 (d, 2 H, H(2)Ar(3), H(6)Ar(3), J = 8.9);
7.53 (d, 2 H, H(3)Ar(2), H(5)Ar(2), J = 8.7); 8.07 (d, 2 H, H(2)Ar(2), H(6)Ar(2)
J = 8.7); 8.20 (s, 1 H, HTz); 9.04 (s, 1 H, H(4))
,
7e
2958 (С(sp3)—H); 1660 (C=O);
1542 (C=N); 752 (C—Cl)
1.21 (d, 6 H, 2 Me (Pri), J = 6.9); 2.33—2.47, 2.53—2.69 (both m, 1 H each, CH);
2.77—3.04 (m, 3 H); 3.38—3.52 (m, 1 H); 3.67 (s, 3 H, MeO); 6.82 (d, 2 H,
H(3)Ar(1), H(5)Ar(1), J = 8.7); 7.15 (d, 2 H, H(2)Ar(1), H(6)Ar(1), J = 8.7);
7.21—7.48 (m, 4 H); 7.53, 8.09 (both d, 2 H each, H arom., J = 8.6);
8.23 (s, 1 H, HTz); 9.08 (s, 1 H, H(4))
Note. In the 1H NMR spectra, Ar(1) is the aryl substituent in position 7 of 7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdione, Ar(2) is the aryl
substituent in position 4 of the 1,3ꢀthiazole fragment, and Ar(3) is the aryl substituent in position 1 of 7,8ꢀdihydroquinolineꢀ
2,5(1H,6H)ꢀdione.
additional purification was required. It should be emphaꢀ
sized that in all these transformations, it is necessary to
prepare firstly 2ꢀdimethylaminomethylidenecyclohexaneꢀ
1,3ꢀdiones 2a—d by condensation of cyclohexaneꢀ1,3ꢀ
diones 1a—d with DMFDMA and use them in the folꢀ
lowing reactions without isolation. At the same time, mixꢀ
ing of all three reaction components (cyclohexaneꢀ1,3ꢀ
dione, DMFDMA, and (1,3ꢀthiazolꢀ2ꢀyl)acetonitrile) can
result in the formation of nitrile—DMFDMA adducts
that are inert to 1,3ꢀdicarbonyl compounds.5
Interestingly, the roomꢀtemperature reaction in the
presence of an equivalent amount of piperidine gave
piperidinium 2ꢀ[2ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ2ꢀyl)ꢀ2ꢀcyanoꢀ
ethenyl]ꢀ3ꢀoxocyclohexꢀ1ꢀenꢀ1ꢀolates 5a,b (see Tables 1, 2).
Although such salts have been isolated earlier,5,7—10 we
believe that their reaction potential is still to be disꢀ
covered. Further heating of enolates 5 in acetic acid
resulted in their cyclization into 7,8ꢀdihydroquinolineꢀ
2,5(1H,6H)ꢀdiones 4, probably via the Dimrothꢀlike
rearrangement.5

3ꢀ(1,3ꢀThiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolinediones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 2, February, 2008
425
Scheme 3
Reagents and conditions: i. AcOH, 20 °C, 15 min.
In the individual state, salts 5 are sufficiently stable for
storage and can be used in reactions with Nꢀnucleophiles.
Salts 5 easily react with aromatic amines. For instance,
stirring of a mixture of enolate 5a and aniline 6b in acetic
acid at room temperature for 15 min (method A) afforded
the target 3ꢀ[4ꢀ(4ꢀchlorophenyl)ꢀ1,3ꢀthiazolꢀ2ꢀyl]ꢀ7,7ꢀ
dimethylꢀ1ꢀ(4ꢀmethylphenyl)ꢀ7,8ꢀdihydroquinolineꢀ2,5ꢀ
(1H,6H)ꢀdione (7b) (Scheme 3; see Tables 1, 2).
tion of aniline 6 in acetic acid gave products 7 in good
yields that need no additional purification (see Tables 1,
2). It is worth noting that the total yields of compounds 7
with respect to cyclohexaneꢀ1,3ꢀdiones 1 were appreꢀ
ciably higher in the case of the “one pot” method B (see
Table 1).
The structures of the compounds obtained were
1
unambiguously determined from their H NMR and IR
The conclusion about the formation of 1ꢀarylꢀ
7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdione 7b rather than
the alternative 2ꢀ(arylimino)ꢀ2,6,7,8ꢀtetrahydroꢀ5Hꢀ
chromenꢀ5ꢀone 8 (see Scheme 3) was drawn from NOE
data. For instance, irradiation of the sample at a resoꢀ
nance frequency of the methylene protons in the cycloꢀ
hexane fragment (δ 2.41) gave rise to NOE at the protons
of the methyl groups in position 7, the CH groups in the
orthoꢀposition of the aromatic substituent of the pyridone
ring, and the proton in position 4 of 1ꢀarylꢀ7,8ꢀdihydroꢀ
quinolineꢀ2,5(1H,6H)ꢀdione 7b (see Scheme 3). The
nuclear Overhauser effect at the CH groups in the
orthoꢀposition of the aromatic substituent is possible only
for structure 7b, not for the alternative structure 8.
NꢀSubstituted 3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ
2,5(1H,6H)ꢀdiones 7 can also be obtained in three steps
by using a “one pot” procedure (method B) without isolaꢀ
tion of enamines 2 or intermediate salts 5 (Scheme 4).
For instance, stirring of a mixture of 2ꢀdimethylaminoꢀ
methylidenecyclohexaneꢀ1,3ꢀdione 2, nitrile 3, and piperiꢀ
dine in PriOH at room temperature for 2.5—3 h followed
by removal of the solvent in vacuo and addition of a soluꢀ
spectra and elemental analysis data, as well as from an
analysis of the literature data. For instance, the 1H NMR
spectra of 7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdiones 4
show a singlet at δ 8.79—8.88 for the CH proton in posiꢀ
tion 4 of the pyridine fragment, a singlet at δ 8.00—8.80
(depending on the aryl substituent in the thiazole fragꢀ
ment) for the proton in position 5 of the thiazole ring (for
R4 = H), and a broadened signal at δ 12.83—12.97 for the
NH proton. This lowꢀfield signal is absent from the specꢀ
tra of Nꢀsubstituted derivatives 7; instead, they contain
the corresponding set of signals for the aryl substituent.
The IR spectra of compounds 4 show absorption bands
at 3318—3401 (N—H stretching vibrations), 2852—2968
(C—H stretching vibrations in the aliphatic system), and
1643—1650 cm–1 (C=O vibrations). The nitro group in
derivatives 4a and 5b is represented by two bands at 1347
(νs) and 1528 cm–1 (νas). In the case of salts 5, the ν(C=O)
band is substantially shifted to the shorter wavelengths because
of delocalization of the negative charge over the enolate
anion of the 1,3ꢀdicarbonyl fragment (1546—1551 cm–1)
and a signal for the cyano group appears at 2200—2220 cm–1.
When passing from 7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀ

426
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 2, February, 2008
Dzhavakhishvili et al.
Scheme 4
pounds were commercial chemicals. Melting points were deterꢀ
mined on a Kofler hot stage. 1H NMR spectra were recorded on
a Varian Mercury VXꢀ200 instrument in DMSOꢀd6 (200 MHz).
IR spectra were recorded on a Specord Mꢀ82 instrument (pellets
with KBr). Elemental analysis was carried out on an EuroVector
EAꢀ3000 instrument. All the microwaveꢀassisted reactions were
carried out in an EmryseTM Creator EXP microwave system
(Biotage, Uppsala) in hermetically sealed vessels for microwave
synthesis (initial radiation power 300 W (Normal option). The
reaction time corresponded to the period of time during which
the reaction mixture was kept at a given temperature.
3ꢀ(4ꢀArylꢀ1,3ꢀthiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ
2,5(1H,6H)ꢀdiones 4a—d (general procedure A). A mixture of
cyclohexaneꢀ1,3ꢀdione 1 (2 mmol) and DMFDMA (2 mmol)
was stirred at room temperature for 5 min. The resulting
2ꢀdimethylaminomethylidenecyclohexaneꢀ1,3ꢀdione 2 was
refluxed with 2ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ2ꢀyl)acetonitrile 3 (2 mmol),
four drops (~0.15 mL) of piperidine, and BunOH (2.0 mL) for
10 min. The reaction was accompanied by the formation of a
voluminous precipitate. After cooling, the crystalline precipitate
was filtered off, washed with ethanol (1.0 mL), and dried at 80
°C. The yields and physicochemical characteristics of compounds
4a—d are given in Tables 1 and 2.
General procedure B. A mixture of cyclohexaneꢀ1,3ꢀdione 1
(2 mmol) and DMFDMA (2 mmol) was stirred at room temꢀ
perature for 5 min in a vessel for microwave synthesis (for the
reaction mixture volumes V = 0.5—2.5 mL). 2ꢀ(4ꢀArylꢀ1,3ꢀ
thiazolꢀ2ꢀyl)acetonitrile 3 (2 mmol), four drops (~0.15 mL)
of piperidine, and PriOH (1.0 mL) were added to the resulting
2ꢀdimethylaminomethylidenecyclohexaneꢀ1,3ꢀdione 2. The vesꢀ
sel was sealed and the reaction mixture was subjected to microꢀ
wave irradiation at 100 °C for 5 min, the gage pressure of the
reaction mixture being 8—9 atm. On cooling, the crystalline
precipitate that formed was filtered off, washed with PriOH
(1.0 mL), and dried at 80 °C. The physicochemical characteristics
of the products obtained were identical with those of compounds
4a—d synthesized according to method A (see Tables 1, 2).
Piperidinium 2ꢀ[2ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ2ꢀyl)ꢀ2ꢀcyanoethenyl]ꢀ
3ꢀoxocyclohexꢀ1ꢀenolates 5a,b (general procedure). A mixture
of cyclohexaneꢀ1,3ꢀdione 1 (10 mmol) and DMFDMA (10 mmol)
was stirred at room temperature for 5 min. 2ꢀ(4ꢀArylꢀ1,3ꢀthiazolꢀ
2ꢀyl)acetonitrile 3 (10 mmol), piperidine (10 mmol), and PriOH
(10.0 mL) were added to the resulting 2ꢀdimethylaminoꢀ
methylidenecyclohexaneꢀ1,3ꢀdione 2. The reaction mixture was
stirred at room temperature for 2.5—3 h. The yellow crystalline
precipitate that formed was filtered off and dried at room temꢀ
perature. The yields and physicochemical characteristics of comꢀ
pounds 5a,b are given in Tables 1 and 2.
3e: R3 = 4ꢀBrC6H4, R4 = H;
6: R5 = H (a), 4ꢀMe (b), 3ꢀF (c), 4ꢀOMe (d), 4ꢀPri (e)
7
a
b
c
d
e
R1
Me
Me
Me
H
R2
Me
Me
Me
H
R3
R4
H
H
Me
H
H
R5
H
4ꢀBrC6H4
4ꢀClC6H4
4ꢀMeC6H4
4ꢀClC6H4
4ꢀClC6H4
4ꢀMe
3ꢀF
4ꢀOMe
4ꢀPri
H
4ꢀMeOC6H4
diones 4 to Nꢀsubstituted derivatives 7, the absorption
band at 3318—3401 cm–1 (N—H group of the pyridinꢀ2ꢀ
one) disappears from the IR spectra.
To sum up, we developed both stepwise (with isolaꢀ
tion of intermediate 2ꢀ[2ꢀ(4ꢀarylthiazolꢀ2ꢀyl)ꢀ2ꢀcyanoꢀ
ethenyl]ꢀ3ꢀoxocyclohexꢀ1ꢀenꢀ1ꢀolates 5) and “one pot”
methods for the synthesis of 3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ
7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀdiones 4 and 1ꢀarylꢀ
3ꢀ(1,3ꢀthiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ2,5(1H,6H)ꢀ
diones 7. The methods proposed for isolation of interꢀ
mediate enolates 5 as piperidinium salts provide the possibility
to apply them in the further synthesis of novel heterocycles.
1ꢀArylꢀ3ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolineꢀ
2,5(1H,6H)ꢀdiones 7a—e (general procedure A). Piperidinium
2ꢀ[2ꢀ(4ꢀarylꢀ1,3ꢀthiazolꢀ2ꢀyl)ꢀ2ꢀcyanoethenyl]ꢀ3ꢀoxocyclohexꢀ
1ꢀenolate 5 (2 mmol) was added to a solution of aromatic amine
6 (2.2 mmol) in acetic acid (2 mL). The reaction mixture was
stirred at room temperature for 15 min. The white precipitate
that formed was filtered off, washed with water (2×2 mL),
and dried at 80 °C. The yields and physicochemical and
spectroscopic characteristics of compounds 7a—e are given in
Tables 1 and 2.
Experimental
Substituted 5ꢀRꢀcyclohexaneꢀ1,3ꢀdiones were prepared acꢀ
cording to a known procedure.11 (1,3ꢀThiazolꢀ2ꢀyl)acetonitriles
were synthesized by the Hantzsch reaction of ωꢀbromoacetoꢀ
phenones with 2ꢀcyanothioacetamide.12 The other starting comꢀ
General procedure B. A mixture of cyclohexaneꢀ1,3ꢀdione 1
(2 mmol) and DMFDMA (2 mmol) was stirred at room temꢀ
perature for 5 min. 2ꢀ(4ꢀArylꢀ1,3ꢀthiazolꢀ2ꢀyl)acetonitrile 3

3ꢀ(1,3ꢀThiazolꢀ2ꢀyl)ꢀ7,8ꢀdihydroquinolinediones
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 2, February, 2008
427
(2 mmol), piperidine (2 mmol), and PriOH (5.0 mL) were added
to the resulting 2ꢀdimethylaminomethylidenecyclohexaneꢀ
1,3ꢀdione 2. The reaction mixture was stirred at room temperaꢀ
ture for 2.5—3 h. The solvent was removed in vacuo. The resultꢀ
ing crystalline precipitate was stirred with a solution of aniline 6
(2 mmol) in acetic acid at room temperature for 15 min. The
precipitate that formed was filtered off, washed with water (2×2 mL),
and dried at 80 °C. The physicochemical characteristics of the
products obtained were identical with those of compounds 7a—e
synthesized according to method A (see Tables 1, 2).
5. N. Yu. Gorobets, B. H. Yousefi, F. Belaj, C. O. Kappe,
Tetrahedron, 2004, 60, 8633.
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cal Chemistry, Eds R. Mannhold, H. Kubinyi, G. Folkers,
Wiley—VCH Verlag GmbH, Weinheim, 2005, 25, 409 pp.
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Geterotsikl. Soedin., 1991, 1199 [Chem. Heterocycl. Compd.,
1991, 27, 960 (Engl. Transl.)].
9. S. Yu. Ryabova, Yu. I. Trofimkin, L. M. Alekseeva, L. S.
Khabarova, V. G. Granik, Khim. Geterotsikl. Soedin., 1991,
343 [Chem. Heterocycl. Compd., 1991, 27, 278 (Engl. Transl.)].
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Transl.)].
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Received March 22, 2007;
in revised form August 1, 2007