SYNTHESIS AND SOME REACTIONS OF 3-SUBSTITUTED 1,4-BIS-(4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-6-YLOXY)BUTANES

Article abstract of DOI:10.1135/cccc19952137

Condensations of 1,4-bis(4-aminophenoxy)butane Ia and its N,N'-dimethyl derivative Ib with substituted diethyl malonates gave 1,4-bis(4-hydroxy-2-oxo-1,2-dihydroquinolin-6-yloxy)butanes IIa-IIf.From these compounds, 1,4-bis(3-halogeno-2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butanes IIIa-IIIg and 1,4-bis(3-hydroxy-2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butanes IIIh-IIIm were prepared.

Full text of DOI:10.1135/cccc19952137

Substituted 6,6’-(Tetramethylenedioxy)bis(2-quinolones)
2137
SYNTHESIS AND SOME REACTIONS OF 3-SUBSTITUTED 1,4-BIS-
(4-HYDROXY-2-OXO-1,2-DIHYDROQUINOLIN-6-YLOXY)BUTANES*
a
a
b
Antonin KLASEK , Stanislav KAFKA and Thomas KAPPE
a Department of Environmental Chemistry and Technology,
Technical University of Brno, 762 72 Zlín, Czech Republic
b Institute of Organic Chemistry,
University of Graz, A-8010 Graz, Austria
Received May 5, 1995
Accepted September 21, 1995
Condensations of 1,4-bis(4-aminophenoxy)butane Ia and its N,N′-dimethyl derivative Ib with sub-
stituted diethyl malonates gave 1,4-bis(4-hydroxy-2-oxo-1,2-dihydroquinolin-6-yloxy)butanes IIa–IIf.
From these compounds, 1,4-bis(3-halogeno-2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butanes
IIIa–IIIg and 1,4-bis(3-hydroxy-2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butanes IIIh–IIIm were
prepared.
In our previous article1, we have published the synthesis of some N-nitroso and N-(2-
methyl-2-nitropropyl) derivatives of 1,4-bis(4-aminophenoxy)butane (Ia) and its N,N′-
dimethyl derivative Ib, which act as improvers of dynamic properties of vulcanized
rubber.
The amines Ia and Ib are readily available1–4 and represent interesting starting ma-
terial for the synthesis of bis(heteroaryl)alkane systems. From the literature data, how-
ever, only a few potential biologically active heterocycles on their basis were prepared:
N,N′-bis(imidazolinylphenoxy)butanes5,6 (lipoxygenase inhibiting antiallergics),
bis(benzimidazolyloxy)butanes7 (anthelmintics), and bis(pyrimidiniumaminophenoxy)-
butanes8 with trypanocidic activity.
In this article, we described the utilization of diamines Ia and Ib for the synthesis of
bis(4-hydroxy-2-oxo-1,2-dihydroquinolinyloxy)butanes and some of their derivatives.
Because many of simple derivatives of 4-hydroxy-2-quinolone are biologically active9–15
the biological activity of presented compounds could be expected.
,
From diamines I, six 1,4-bis(4-hydroxy-2-oxo-1,2-dihydroquinolinyloxy)butanes
(IIa–IIf) were prepared (Scheme 1) by the known condensation of anilines with sub-
* Presented at the 4th Blue Danube Symposium on Heterocyclic Chemistry, St. Polten, Austria, June 22–25,
1994.
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

2138
Klasek, Kafka, Kappe:
stituted diethyl malonates (e.g. refs12,16,17). Unsuccessful were condensations of
diamines I with unsubstituted diethyl malonate, in which only polymeric substances
were obtained. When diethyl phenylthiomalonate was used for the condensation, a
polymer and almost theoretical amount of diphenyl disulfide were isolated.
From compounds IIa–IIf, bis(3-halogeno-2,4-dioxo-1,2,3,4-tetrahydroquinolinyl-
oxy)butanes IIIa–IIIg were obtained (Scheme 1) by their bromination in different reac-
tion media or by chlorination with sulfuryl chloride in analogy with refs12,17,18. By the
reduction of 3-bromo derivatives IIIa and IIIb with zinc in acetic acid or with hydrazine
hydrate in ethanol, 4-hydroxyquinolones IIa and IIb, respectively, were obtained.
Bis(3-hydroxy-2,4-dioxo-1,2,3,4-tetrahydroquinolinyloxy)butanes IIIh–IIIm were pre-
pared by oxidation of compounds IIa–IIf with peroxyacetic acid according to ref.18. It
was presented18, that simple 3-hydroxy-2,4-quinolinediones can also be obtained by
oxidation of 4-hydroxy-2-quinolones with nitric acid. However, the application of this
method on our compounds of type II gave only mixtures of several compounds with
minor content of the expected 3-hydroxy derivatives. Probably, nitration of the rela-
tively active benzene nucleus takes place simultaneously with oxidation in position 3 of
quinoline nucleus.
Some of the prepared compounds exhibit broad melting points and, in some cases,
melting and a new crystallization can be observed during heating (Tables I and II). In
the case of compounds III, this behavior could be due to the fact that these compounds
are mixtures of racemate and mesoform. We assume approximately 1 : 1 ratio of these
components; the preference of formation of one of both diastereoisomers is unlikely
because of long distance between the positions 3 of quinolone moieties in their precur-
sors II. Consequently, negligible stereospecific effect of one of new substituents on the
introduction of the other could be expected. Due to long distance between the chiral
centers in the molecules of substances III and, therefore, to a small probability of their
interactions, only one spot on their thin-layer chromatograms (in several solvent sys-
tems) and the absence of any signal doubling in their NMR spectra are observed. All
attempts to separate the diastereoisomers by means of recrystallization were unsuccess-
ful. Because some compounds of the type II, which contain no chirality centers, exhibit
also phase changes and oriented crystallization during further heating, the observed
behavior of all substances under investigation can be connected with the shape of the
molecule which principally enables the formation of the liquid-crystalline phase.
All elemental analyses were satisfactory (Tables I and II), the IR and 1H NMR spectra of
prepared compounds are presented in Table III.
EXPERIMENTAL
The melting points were determined on a Kofler block and are uncorrected. Infrared spectra were
1
taken in potassium bromide pellets on a Perkin–Elmer 298 spectrophotometer. The H NMR spectra
were recorded on a Varian–Gemini 200 instrument using tetramethylsilane as an internal standard in
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Substituted 6,6’-(Tetramethylenedioxy)bis(2-quinolones)
2139
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

2140
Klasek, Kafka, Kappe:
hexadeuteriodimethyl sulfoxide. All reactions were monitored by thin layer chromatography, carried out
on 0.2 mm silica gel (Kavalier, Czech Republic) plates by using the solvent system chloroform–ethanol
(9 : 1 and/or 19 : 1); for detection UV light and/or iodine vapours were used. Preparative column
chromatography was carried out on silica gel 0.10/0.16 mm (Kavalier, Czech Republic).
General Procedure for the Synthesis of 1,4-Bis(4-hydroxy-2-oxo-1,2-dihydroquinolin-6-yloxy)
butanes II
Method A. The mixture of respective diamine I (0.02 mol) and substituted diethyl malonate (0.044 mol)
was heated on a metal bath at 180–200 °C for 0.5 h and then at 270–285 °C. Evolved ethanol was
collected and weighed. When the near theoretical quantity of ethanol was obtained, the mixture was
cooled, the solid product was crushed, washed several times with petroleum ether and/or diethyl ether
and recrystallized. In the case of chromatographically impure product, purification by dissolving in
TABLE I
Characteristic data of substituted 1,4-bis(4-hydroxy-2-oxo-1,2-dihydroquinolin-6-yloxy)butanes II
Calculated/Found
Yield, %
(Method)
M.p., °C
Formula
(M.w.)
Compound
(Solventa)
% C
% H
% N
IIa
IIb
IIc
IId
87 (A)
74 (B)
302–307
C30H36N2O6
(520.6)
69.21
68.92
6.97
6.91
5.38
5.52
(BuOH–DMF)
92 (A)
68 (B)
292–302
C36H32N2O6
(588.7)
73.45
73.16
5.48
5.39
4.76
4.81
(DMF)
72 (A)
303–309
C34H28N2O8
(560.6)
72.85
72.87
5.03
4.82
5.00
5.30
(DMSO)
93 (A)
106–112,
204–209
C32H40N2O6
(548.7)
70.05
69.68
7.35
7.47
5.11
4.79
(BuOH–EtOH)
IIe
IIf
96 (A)
95 (C)
158–162,
284–288
C38H36N2O6
(616.7)
74.01
73.72
5.88
5.80
4.54
4.72
(BuOH–DMF)
83 (A)
300–312
C36H32N2O6
(588.7)
73.45
73.19
5.48
5.43
4.76
4.80
(DMSO)
a BuOH 1-butanol, EtOH ethanol.
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Substituted 6,6’-(Tetramethylenedioxy)bis(2-quinolones)
2141
TABLE II
Characteristic data of 3-substituted 1,4-bis(2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butanes III
Calculated/Found
Yield, %
(Method)
M.p., °C
Formula
(M.w.)
Compound
(Solventa)
% C
% H
% N
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
78 (A)
83 (C)
193–194
(EtOH)
C30H34Br2N2O6
(678.4)
53.11
53.40
5.05
4.91
4.13
3.71
74 (D)
207–209
(EtOH)
C36H30Br2N2O6
(746.5)
57.93
57.70
4.05
3.91
3.75
4.02
24b(D)
289–308
C34H26Br2N2O6
(718.4)
56.84
56.45
3.65
3.96
3.90
4.12
68 (B)
76 (C)
54–58
(MeOH)
C32H38Br2N2O6
(706.5)
54.40
54.36
5.42
5.16
3.96
3.75
88 (D)
57 (E)
96
128–129
(benzene)
C38H34Br2N2O6
(774.5)
58.93
58.79
4.42
4.33
3.62
3.71
97–100
C36H30Br2N2O6
(746.5)
57.93
57.63
4.05
4.11
3.75
3.91
IIIg
IIIh
150–160
C36H30Cl2N2O6
(657.5)
65.76
65.23
4.60
4.69
4.26
4.26
96
132–142,
218–226
(MeOH)
C30H36N2O8
(552.6)
65.20
65.25
6.57
6.44
5.07
4.69
IIIi
96
152–154,
276–281
(EtOH)
C36H32N2O8
(620.7)
69.67
69.51
5.20
5.17
4.51
4.38
IIIj
IIIk
IIIl
87
78
98
299–308
(BuOH–DMF)
C34H28N2O8
(592.6)
68.91
68.60
4.76
4.61
4.73
4.45
73–76
(benzene)
C32H40N2O8
(580.7)
66.19
65.98
6.94
6.80
4.82
4.41
86–90,
182–189
(benzene)
C38H36N2O8
(648.7)
70.36
70.19
5.59
5.50
4.32
4.18
IIIm
96
310–328
(MeOH–DMF)
C36H32N2O8
(620.7)
69.67
69.53
5.20
5.15
4.51
4.28
a
b
MeOH methanol, EtOH ethanol, BuOH 1-butanol. Purified by column chromatography on silica
gel, eluent chloroform–ethanol 96 : 4.
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

2142
Klasek, Kafka, Kappe:
TABLE III
Spectroscopic data for 1,4-bis(4-hydroxy-2-oxo-1,2-dihydroquinolin-6-yloxy)butanes II and 1,4-
bis(2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butanes III
~
Compound
IR (ν, cm–1)
1H NMR (δ, ppm)a
IIa
3 540–3 100 br, 2 952 m, 2 925 m,
0.93 t, 3 H, J = 7.0 (CCH3); 1.23–1.52 m, 4 H
2 862 m, 1 642 s, 1 620 sh, 1 603 s, (H-2 and H-3 of butyl); 1.92 s, 2 H (OCCH2);
1 561 m, 1 507 s, 1 462 m, 1 428 m, 2.59 t, 2 H, J = 7.0 (H-1 of butyl); 4.08 s, 2 H
1 270 s, 1 234 s, 1 218 s, 1 195 sh,
1 165 m, 1 136 m
(OCH2); 7.12 dd, 1 H, J = 8.0 and 2.0 (H-7);
7.21 d, 1 H, J = 8.0 (H-8); 7.40 d, 1 H, J = 2.0
(H-5); 9.93 s, 1 H (OH); 11.20 s, 1 H (NH)
IIb
IIc
IId
3 600–2 800 br, 1 655 sh, 1 645 s,
1.95 s, 2 H (OCCH2); 3.95 s, 2 H (ArCH2);
1 620 s, 1 612 sh, 1 604 s, 1 557 m, 4.09 brs, 2 H (OCH2); 7.16 dd, 1 H, J = 8.0 and
1 508 m, 1 453 m, 1 418 m, 1 382 m, 2.0 (H-7); 7.20–7.32 m, 6 H (H-8 and arom.);
1 325 m, 1 271 m, 1 240 sh, 1 230 s, 7.48 d, 1 H, J = 2.0 (H-5); 10.31 brs,
1 215 m, 1 200 m
1 H (OH); 11.30 s, 1 H (NH)
3 600–2 400 br, 1 648 s, 1 614 s,
1 601 s, 1 512 s, 1 477 m, 1 450 m,
1 370 m, 1 293 s, 1 234 s, 1 201 s,
1 050 m, 1 030 m, 821 m, 710 s,
660 m
1.88–2.02 m, 2 H (OCCH2); 4.04–4.18 m, 2 H
(OCH2); 7.20 dd, 1 H, J = 9 and 2.6 (H-7);
7.23–7.46 m, 6 H (phenyl and H-8); 7.50 d,
1 H, J = 2.6 (H-5); 10.00 brs, 1 H (OH); 11.35 s,
1 H (NH)
3 500–2 900 br, 2 955 m, 2 930 m,
0.90 t, 3 H, J = 7.0 (CCH3); 1.27–1.47 m, 4 H,
2 875 m, 1 634 m, 1 611 s, 1 581 s,
(H-2 and H-3 of butyl); 1.96 brs, 2 H (OCCH2);
1 509 m, 1 465 m, 1 345 m, 1 282 s, 2.63 t, 2 H, J = 7.0 (H-1 of butyl); 3.57 s, 3 H
1 225 m, 1 212 s, 1 193 s, 816 m
(NCH3); 4.13 brs, 2 H (OCH2); 7.22 dd, 1 H,
J = 9.0 and 2.6 (H-7); 7.40 d,
1 H, J = 9.0 (H-8); 7.51 d, 1 H, J = 2.6 (H-5);
9.98 brs, 1 H (OH)
IIe
IIf
3 600–2 800 br, 1 640 sh, 1 612 s,
1 565 s, 1 510 s, 1 491 m, 1 420 m,
1 399 m, 1 351 m, 1 332 m, 1 269 m, 7.15–7.30 m, 6 H (H-7 and arom.); 7.43 d, 1 H,
1 235 s, 1 218 s, 1 170 m, 971 m,
699 m
1.96 s, 2 H (OCCH2); 3.58 s, 3 H (NCH3);
4.00 s, 2 H (ArCH2); 4.15 s, 2 H (OCH2);
J = 8.0 (H-8); 7.58 d, 1 H, J = 2.0 (H-5);
10.35 brs, 1 H (OH)
3 400–2 700 br, 1 638 s, 1 618 s,
1 603 s, 1 580 s, 1 514 s, 1 458 m,
1.94–2.04 m, 2 H (OCCH2); 3.61 s, 3 H (CH3);
4.16 t, 2 H, J = 7 (OCH2); 7.31 dd, 1 H, J = 9
1 340 m, 1 300 m, 1 263 m, 1 229 m, and 2.6 (H-7); 7.36–7.45 m, 5 H (phenyl);
1 210 s, 1 118 m, 1 054 m, 1 023 m, 7.51 d, 1 H, J = 9 (H-8); 7.59 d, 1 H, J = 2.6
864 m, 807 m, 748 m, 696 m
(H-5)
IIIa
3 200–2 800 br, 1 705 s, 1 667 s,
0.85 t, 3 H, J = 7.0 (CCH3); 1.15–1.22 m, 2 H
1 658 sh, 1 502 s, 1 470 m, 1 425 m, (H-3 of butyl); 1.22–1.40 m, 2 H (H-2 of butyl);
1 341 m, 1 262 m, 1 199 m, 824 m
1.90 s, 2 H (OCCH2);2.43 t, 2 H, J = 8.0 (H-1
of butyl); 4.10 s, 2 H (OCH2); 7.12 dd, 1 H, J =
8.0 and 2.0 (H-7); 7.30–7.40 m, 2 H (H-5, H-8);
11.19 s, 1 H (NH)
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

Substituted 6,6’-(Tetramethylenedioxy)bis(2-quinolones)
2143
TABLE III
(Continued)
~
Compound
IR (ν, cm–1)
1H NMR (δ, ppm)a
IIIb
3 400–2 800 br, 1 702 s, 1 667 s, 1 658 sh, 1.87 s, 2 H (OCCH2); 3.87 s, 2 H
1 619 m, 1 501 s, 1 428 m, 1 348 s, 1 278 (ArCH2); 4.08 s, 2 H (OCH2); 7.04 dd,
m, 1 236 m, 1 190 m, 702 m
1 H, J = 8.0 and 2.0 (H-7); 7.15–7.37 m,
7 H (arom.); 11.25 s, 1 H (NH)
1.82–1.97 m, 2 H (OCCH2); 4.00–4.16 m,
2 H (OCH2); 7.05–7.55 m, 8 H (arom.);
11.34 s, 1 H (NH)
IIIc
IIId
1 708 s, 1 667 s, 1 615 m, 1 500 s,
1 469 m, 1 447 m, 1 420 m, 1 341 s,
1 271 m, 1 215 m, 1 182 m, 825 m,
735 m, 696 m, 659 m, 637 m
2 940 m, 2 868 m, 1 703 sh, 1 696 s,
1 664 s, 1 656 sh, 1 617 m, 1 587 m,
0.86 t, 3 H, J = 7.5 (CCH3); 1.08–1.26 m,
2 H (H-3 of butyl); 1.26–1.44 m, 2 H
1 501 s, 1 468 s, 1 441 s, 1 348 s, 1 290 s, (H-2 of butyl); 1.93 s, 2 H (OCCH2);
1 235 m, 1 213 m, 1 172 m, 1 125 m,
1 087 m, 1 041 m, 819 m
2.38–2.58 m, 2 H (H-1 of butyl); 3.45 s,
3 H (NCH3); 4.17 s, 2 H (OCH2);
7.42 brs, 3 H (arom.)
IIIe
IIIf
3 100–2 800 br, 1 704 s, 1 693 s,
1 668 sh, 1 611 s, 1 500 s, 1 468 s,
1 441 s, 1 351 s, 1 292 m, 1 241 m,
1 212 m, 1 131 m, 819 m, 702 m
1 705 s, 1 671 s, 1 620 m, 1 590 m,
1.92 brs, 2 H (OCCH2); 3.41 s, 3 H
(NCH3); 3.91 s, 2 H (ArCH2); 4.15 brs,
2 H (OCH2); 7.10–7.45 m, 8 H (arom.)
1.80–1.90 m, 2 H (OCCH2); 3.47 s, 3 H
1 505 s, 1 471 s, 1 443 s, 1 349 s, 1 299 s, (CH3); 4.00–4.10 m, 2 H (OCH2);
1 240 m, 1 225 m, 1 199 m, 1 135 m,
740 m
7.20–7.50 m, 8 H (arom.)
IIIg
IIIh
1 710 s, 1 678 s, 1 582 m, 1 501 s,
1 468 s, 1 440 s, 1 341 m, 1 295 s,
1 286 sh, 1 238 m, 1 204 m, 1 129 m,
1 052 m, 1 036 m, 812 m, 760 m, 690 m
3 500–3 200 br, 2 955 m, 2 925 m, 1 706
m, 1 670 s, 1 619 m, 1 500 s, 1 468 m,
1 420 m, 1 342 m, 1 269 m, 1 219 m,
1 192 m, 1 163 m, 824 m
1.83–1.93 m, 2 H (OCCH2); 3.49 s, 3 H
(CH3); 4.02–4.14 m, 2 H (OCH2);
7.28–7.47 m, 8 H (arom.)
0.78 t, 3 H, J = 7.0 (CCH3); 1.08–1.40 m,
4 H (H-2 and H-3 of butyl); 1.62–1.80 m,
2 H (H-1 of butyl); 1.87 s, 2 H (OCCH2);
4.06 s, 2 H (OCH2); 5.63 s, 1 H (OH);
7.02 dd, 1 H, J = 7.0 and 2.0 (H-7); 7.20
d, 1 H, J = 2.0 (H-5); 7.25 d, 1 H, J = 7.0
(H-8); 10.61 s, 1 H (NH)
IIIi
IIIj
3 600–2 800 br, 1 722 sh, 1 712 s,
1 671 s, 1 653 s, 1 618 s, 1 498 s,
1 471 m, 1 452 m, 1 420 m, 1 345 m,
1 270 m, 1 219 s, 1 179 m, 698 m
1.89 brs, 2 H (OCCH2); 3.07 s, 2 H
(ArCH2); 4.07 brs, 2 H (OCH2); 5.93 s,
1 H (OH); 6.90–7.33 m, 8 H (arom.);
10.68 s, 1 H (NH)
3 640–3 000 br, 2 942 m, 1 640 s, 1 608 s, 1.88–2.02 m, 2 H (OCCH2); 4.06–4.18 m,
1 595 s, 1 502 m, 1 468 m, 1 445 m,
1 430 m, 1 392 m, 1 364 m, 1 288 s,
1 228 s,1 194 s, 1 042 m, 1 022 m, 817 m,
782 m, 750 m, 705 s, 695 m, 653 m
2 H (OCH2); 7.20–7.5 m, 8 H (Ar-H);
11.16 brs, 1 H (NH)
Collect. Czech. Chem. Commun. (Vol. 60) (1995)

2144
Klasek, Kafka, Kappe:
TABLE III
(Continued)
Compound
IIIk
~
IR (ν, cm–1)
1H NMR (δ, ppm)a
3 550–3 300 br, 2 960 m, 1 710 s, 1 661 s, 0.76 t, 3 H, J = 6.6 (CCH3); 1.06–1.28 m,
1 501 s, 1 468 s, 1 352 m, 1 305 m, 1 285 4 H (H-2 and H-3 of butyl); 1.62–1.77 m,
m, 1 225 s, 1 179 m, 1 114 m
2 H (H-1 of butyl); 1.91 brs, 2 H
(OCCH2); 3.38 s, 3 H (NCH3); 4.11 brs,
2 H (OCH2); 5.70 s, 1 H (OH); 7.26–7.37
m, 3 H (arom.)
IIIl
3 600–3 100 br, 2 930 m, 2 870 m, 1 722
sh, 1 708 s, 1 662 s, 1 640 sh, 1 613 m,
1 585 m, 1 498 s, 1 469 s, 1 442 s, 1 351
m, 1 272 s, 1 223 s, 1 128 m, 1 103 s,
1 121 m, 700 m
1.94 brs, 2 H (OCCH2); 3.03 s, 2 H
(ArCH2); 3.31 s, 3 H (NCH3); 4.12 brs,
2 H (OCH2); 5.96 s, 1 H (OH); 6.88–7.32
m, 8 H (arom.)
IIIm
3 300–3 100 br, 3 042 m, 2 940 m, 2 860
1.98 brs, 2 H (OCCH2); 3.62 s, 3 H (CH3);
m, 1 631 s, 1 611 s, 1 598 s, 1 572 s,
4.16 brs, 2 H (OCH2); 7.30–7.65 m, 8 H
1 508 s, 1 473 m, 1 450 m, 1 438 m, 1 335 (arom.)
m, 1 295 m, 1 259 m, 1 222 s, 1 205 s,
1 178 m, 1 112 m, 1 018 m, 800 s, 689 m
a According to the symmetry of the measured compounds, the numbers of hydrogen atoms are calcu-
lated for a half of the molecule.
0.5 M sodium hydroxide, filtration, precipitation with diluted hydrochloric acid and repeated crystal-
lization was carried out.
Method B. The mixture of 3-bromo derivative III (1 mmol), acetic acid (30 ml) and zinc (0.5 g)
was refluxed for 0.5 h. After cooling, the precipitate was filtered with suction, washed with diluted
acetic acid and recrystallized from acetic acid.
Method C. To a stirred suspension of 3-bromo derivative III (1 mmol) in ethanol (30 ml), the
solution of potassium hydroxide (0.4 g, 7 mmol) and hydrazine hydrate (0.2 g, 4 mmol) in ethanol
(20 ml) was added within 10 min at 60 °C. After additional 15 min at this temperature, the mixture
was taken down in vacuo to 15 ml, diluted with water (30 ml) and acidified with diluted (1 : 1)
hydrochloric acid. The precipitate was filtered with suction and recrystallized.
General Procedure for the Synthesis of 1,4-Bis(3-bromo-2,4-dioxo-1,2,3,4-tetrahydroquinolin-
6-yloxy)butanes IIIa–IIIf
Method A. To a stirred solution of the corresponding bis(quinolone) II (5 mmol) in acetic acid
(from 60 to 150 ml), bromine (1.9 g, 12 mmol) was added at laboratory temperature within 10 min.
After 15 min of stirring, the solution was filtered and the filtrate was diluted with water. Precipitated
product was filtered with suction, washed with water and recrystallized.
Method B. The procedure is identical with that of method A, the mixture acetic acid–dioxan (9 : 1)
was used as solvent.
Method C. The procedure is identical with that of method A, 0.25 M sodium hydroxide (120 ml)
was used as solvent.
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Substituted 6,6’-(Tetramethylenedioxy)bis(2-quinolones)
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Method D. To a stirred suspension of the corresponding bis(quinolone) II (5 mmol) in chloroform
(60 ml), bromine (1.9 g, 12 mmol) was added at laboratory temperature within 10 min. After 15 min
of stirring the solution was filtered, the filtrate was evaporated in vacuo to dryness and the residue
was recrystallized.
Method E. The procedure is identical with that of method D, tetrachloroethene was used as reac-
tion medium. The reaction was carried out under cooling with ice bath, the product was precipitated
from the reaction mixture with petroleum ether.
1,4-Bis(2-chloro-1-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-yloxy)butane (IIIg)
To the stirred suspension of compound IIf (3.42 g, 5.81 mmol) in chloroform (116 ml), sulfuryl
chloride (5.23 g, 39.1 mmol) was added. After 7 h boiling under stirring, the mixture was filtered
under suction. The filtrate was taken down in vacuo and the residue was triturated with methanol.
Yield 3.68 g (96%) yellow crystals of the compound IIIg.
General Procedure for the Synthesis of 1,4-Bis(3-hydroxy-2,4-dioxo-1,2,3,4-tetrahydroquinolin-6-
yloxy)butanes IIIh–IIIm
To a stirred solution of respective bis(quinolone) II (5 mmol) in 0.25 M sodium hydroxide (120 ml),
30% peroxyacetic acid (20 ml) was added within 0.5 h at laboratory temperature. After additional 1 h
stirring, the precipitated product was filtered with suction, washed with water, aqueous sodium bicar-
bonate and water till the filtrate was neutral, and recrystallized. All hydroxy derivatives show a
characteristic light blue fluorescence on TLC plates.
The elemental analyses were performed in the Institute of Organic and Analytical Chemistry, Palacky
University, Olomouc. This study was supported by the Grant Agency of the Czech Republic (Grant No.
104/94/0104).
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