Synthesis of fluorine-containing quinoline-2,3-dicarboxylates from products of vicarious nucleophilic substitution of hydrogen in 3-fluoronitroarenes

Article abstract of DOI:10.1007/s11172-009-0026-2

The reactions of 3-fluoro-4-R-6-phenylsulfonylmethylnitrobenzenes with dimethyl fumarate or diethyl maleate in acetonitrile in the presence of an excess of K₂CO³ and a catalytic amount of 18-crown-6 afforded mixtures of dialkyl 6-R-7

Full text of DOI:10.1007/s11172-009-0026-2

Russian Chemical Bulletin, International Edition, Vol. 58, No. 1, pp. 170—175, January, 2009
170
Synthesis of fluorineꢀcontaining quinolineꢀ2,3ꢀdicarboxylates from products
of vicarious nucleophilic substitution of hydrogen in 3ꢀfluoronitroarenes*
S. K. Kotovskaya,a G. A. Zhumabaeva,a V. N. Charushin,a,b and O. N. Chupakhina,b
aUral State Technical University,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 0458. Eꢀmail: kotovskaya@mail.ustu.ru
bI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: chupakhin@ios.uran.ru
The reactions of 3ꢀfluoroꢀ4ꢀRꢀ6ꢀphenylsulfonylmethylnitrobenzenes with dimethyl
fumarate or diethyl maleate in acetonitrile in the presence of an excess of K2CO3 and a
catalytic amount of 18ꢀcrownꢀ6 afforded mixtures of dialkyl 6ꢀRꢀ7ꢀfluoroꢀ and dialkyl
6ꢀRꢀ7ꢀphenylsulfonylquinolineꢀ2,3ꢀcarboxylate Nꢀoxides, as well as dialkyl 6ꢀRꢀ7ꢀfluoroꢀ
quinolineꢀ2,3ꢀcarboxylates (alkyl is methyl or ethyl), which were resolved by column
chromatography and identified by 1H NMR spectroscopy and Xꢀray diffraction.
Key words: vicarious nucleophilic substitution of hydrogen, 4ꢀRꢀ3ꢀfluoronitrobenzenes,
3ꢀfluoroꢀ4ꢀRꢀ6ꢀphenylsulfonylmethylnitrobenzenes, dimethyl fumarate, diethyl maleate,
dimethyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀcarboxylate Nꢀoxides, diethyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ
2,3ꢀcarboxylate Nꢀoxides, dimethyl 6ꢀRꢀ7ꢀphenylsulfonylquinolineꢀ2,3ꢀcarboxylate Nꢀoxides,
diethyl 6ꢀRꢀ7ꢀphenylsulfonylquinolineꢀ2,3ꢀcarboxylate Nꢀoxides, dimethyl 6ꢀRꢀ7ꢀfluoroꢀ
quinolineꢀ2,3ꢀcarboxylates, diethyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀcarboxylates.
The quinoline ring acts as a structural element in a
number of synthetic drugs and natural biologically active
compounds. Thus, Makaluvamine C is known as an effiꢀ
cient antitumor drug of natural origin.1,2 8ꢀ(4ꢀAminoꢀ
1ꢀmethylbutylamino)ꢀ6ꢀmethoxyquinoline (Primaquine)
and 8ꢀ(4ꢀaminopentyl)aminoꢀ6ꢀmethoxyquinoline diꢀ
hydrochloride (Quinocide) are efficient antimalarial
agents.3 4ꢀAminoꢀ8ꢀmethylquinoline and Nꢀ(pꢀacetylꢀ
phenyl)ꢀαꢀarylazoꢀ2ꢀchloroꢀ7ꢀmethoxyquinolinꢀ3´ꢀylazoꢀ
methane exhibit antimicrobial activity,4,5 2ꢀ[4ꢀ(7ꢀchloroꢀ
quinolinꢀ2ꢀyloxy)phenoxy]propanoic acid has antitumor
activity,6 and 4ꢀquinoline hydrazones show tuberculoꢀ
static activity.7 In recent years, the synthesis of fluorineꢀ
containing heterocyclic compounds has attracted considꢀ
erable interest. These compounds have found application
as plant protection chemicals and medicines.8 Among
fluorineꢀsubstituted quinolones and quinolines, there are
compounds exhibiting antibacterial,9,10 antidiabetic,11 or
antitumor12 activities. 5ꢀFluoroprimaquine is an analog
of the known antimalarial drug.13
with diethyl oxaloacetate15 or acetylenedicarboxylates16
are of limited use, because the starting substrates are diffiꢀ
cultly accessible; moreover, aminoaldehydes are unstable.
An efficient method for the construction of fused
heterocycles is based on modifications of nitroarenes by
the oxidative or vicarious nucleophilic substitution of
H
hydrogen (SN ), which allows the introduction of variꢀ
ous substituents in the ortho position with respect to the
nitro group.17—19 At the same time, data on the synthesis
of quinolines by the reactions of nitroarenes with vicariꢀ
ous nucleophiles are scarce.14,20 Data on the synthesis
of fluorinated derivatives of quinolineꢀ2,3ꢀdicarboxylates
are lacking.
H
Earlier, we have reported the application of the SN
approach to the construction of fluorineꢀcontaining
3ꢀaminoꢀ1,2,4ꢀbenzotriazines21 and 3ꢀsulfonylindoles.22
In subsequent studies aimed at examining the scope of the
nucleophilic substitution of hydrogen in nitroarenes, we
developed a procedure for the synthesis of fluorineꢀconꢀ
taining quinolines based on fluoronitroarenes. For our
study, we chose 4ꢀRꢀ3ꢀfluoronitrobenzenes 1a—c, which
were synthesized by the reaction of 3,4ꢀdifluoronitrobenꢀ
zene with the corresponding alcohols or cycloalkylꢀ
amines.21 Earlier, we have shown22 that the vicarious
nucleophilic substitution of hydrogen in nitroarenes 1a—c
Methods for the synthesis of quinolineꢀ2,3ꢀdicarboxyꢀ
late derivatives by the reactions of orthoꢀnitroarenealdeꢀ
hydes with diethyl (diethoxyphosphinyl)succinate14 and
by the condensation of orthoꢀaminoarenecarbaldehydes
* Dedicated to Academician A. I. Konovalov on his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 170—175, January, 2009.
1066ꢀ5285/09/5801ꢀ0170 © 2009 Springer Science+Business Media, Inc.

Fluorinated 2,3ꢀdimethyl(diethyl) quinolinecarboxylates Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
171
Scheme 1
Reagents and conditions: i. ClCH2SO2Ph, KOH/DMSO;
1—13: R = OMe (a), OEt (b),
(c)
ii. K2CO3, 18ꢀcrownꢀ6, MeCN,
R´ = Me (4, 6, 8, 10, 12), Et (5, 7, 9, 11, 13)
or
Compound
R
Yield (%)
R´ = Me
10 12
R´ = Et
9 11 13
for
for
8
1a
1b
OMe
OEt
23 40
25 38
25 20 38 23
27 18 36 25
with chloromethyl phenyl sulfone proceeds selectively
at the ortho position with respect to the nitro group to
form 3ꢀfluoroꢀ4ꢀRꢀ6ꢀphenylsulfonylmethylnitrobenzenes
2a—c in 60—70% yields (Scheme 1).
1c
30 35
30 25 40 28
sulfonylmethylnitroarene 2a—c to the activated double
bond of maleate 4a—c (or fumarate 5a—c). Then the
cyclocondensation involving the nitro group affords comꢀ
pounds 6a—c (or 7a—c). In the course of the reaction,
phenylsulfinic acid is eliminated from intermediates
6a—c (or 7a—c). The anion of the acid reacts with dialkyl
6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀdicarboxylate Nꢀoxides 8a—c
(or 9a—c) to form ipsoꢀsubstitution products 10a—c (or
11a—c). In addition, Nꢀoxides 8a—c (or 9a—c) are parꢀ
tially reduced (most likely, also with phenylsulfinic acid)
to dialkyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀdicarboxylates 12a—c (or
13a—c). The concerted mechanism of forꢀmation of the
quinoline moiety via the cycloaddition involving dienes
3a—c cannot also be excluded from consideration.
It was found that the reactions of 3ꢀfluoroꢀ4ꢀRꢀ
6ꢀphenylsulfonylmethylnitrobenzenes 2a—c with α,βꢀunꢀ
saturated acid esters (dimethyl fumarate or diethyl
maleate) in acetonitrile in the presence of an excess of
K2CO3 as the base and a catalytic amount of 18ꢀcrownꢀ6
afforded mixtures of the following three products: dialkyl
6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀdicarboxylate
Nꢀoxides
(8a—c or 9a—c) (18—30%), dialkyl 6ꢀRꢀ7ꢀphenylsulfonylꢀ
quinolineꢀ2,3ꢀdicarboxylate Nꢀoxides (10a—c or 11a—c)
(35—40%), and dialkyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀdicarꢀ
boxylates (12a—c or 13a—c) (23—30%), which were sepaꢀ
rated by preparative column chromatography.
Apparently, the first step of the reaction involves the
Michael addition of the carbanion of the starting phenylꢀ

172
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Kotovskaya et al.
Table 1. Reaction conditions, yields, melting points, and elemental analysis data for compounds 8a—c and 9a—c
Comꢀ
pound
Т/°С
τ/h
Yield
(%)
M.p./°С
Rf*
M
Found
Calculated
Molecular
formula
(%)
C
H
N
8a
8b
8c
9a
9b
9c
80
80
80
80
80
80
24
24
18
26
26
20
23
25
30
20
18
25
214—215
231—232
236—237
208—210
179—180
245—247
0.32
0.34
0.20
0.28
0.20
0.23
309.27
323.29
364.33
337.32
351.34
392.41
55.98
56.04
55.70
55.73
55.80
56.04
56.90
56.96
58.10
58.12
57.50
58.15
4.67
4.70
4.30
4.36
4.58
4.70
4.70
4.79
5.10
5.16
5.25
5.39
7.63
7.68
4.30
4.33
7.10
7.68
4.10
4.15
3.90
3.98
7.05
7.14
C14H12FNO6
C15H14FNO6
C17H17FN2O6
C16H16FNO6
C17H18FNO6
C19H21FN2O6
* A 2 : 8 ethyl acetate—dichloromethane mixture as the eluent.
1
The H NMR spectra of quinoline Nꢀoxides 8a—c
Experimental
The 1H NMR spectra were recorded on Bruker WPꢀ250
and 9a—c show signals for the protons H(5) and H(8)
at δ 8.53—8.80 and 9.04—9.20, respectively, as characꢀ
teristic doublets with the spinꢀspin coupling constants
4JH(5),F(7) = 8.8—9.6 Hz and JH(8),F(7) = 11.6—13.4 Hz.
Analogous signals for the protons H(5) and H(8) of quinoꢀ
lines 12a—c and 13a—c are shifted upfield by 0.13—0.16
and Bruker DRXꢀ400 spectrometers operating at 250.13 and
400.13 MHz, respectively, with Me4Si as the internal standard.
The mass spectra were obtained on a Varian MATꢀ311A
spectrometer at an accelerating voltage of 3 kW using a direct
inlet system; the ionizing electron energy was 70 eV. The reaction
progress was monitored and the purity of the reaction products
was checked by TLC on Silufol UVꢀ254 plates using dichloroꢀ
methane, ethyl acetate—dichloromethane (1 : 8), and ethyl
acetate—dichloromethane (2 : 8) as the eluents.
3
1
and 0.06—0.40 ppm, respectively. The H NMR spectra
of compounds 10a—c and 11a—c are characterized by the
presence of three singlets for aromatic protons at δ 8.04,
8.70, and 9.25. The mass spectra of all compounds
8a—c—13a—c have molecular ion peaks.
Synthesis of dimethyl (8a—c) and diethyl 6ꢀRꢀ7ꢀfluoroꢀ
quinolineꢀ2,3ꢀdicarboxylate Nꢀoxides (9a—c), dimethyl (10a—c)
and diethyl 6ꢀRꢀ7ꢀphenylsulfonylquinolineꢀ2,3ꢀdicarboxylate
Nꢀoxides (11a—c), and dimethyl (12a—c) and diethyl 6ꢀRꢀ
7ꢀfluoroquinolineꢀ2,3ꢀdicarboxylates (13a—c) (general proceꢀ
dure). Sodium carbonate (2.1 mmol) was added to a solution of
3ꢀfluoroꢀ4ꢀRꢀ6ꢀphenylsulfonylmethylnitrobenzene 2 (0.52 mmol),
dimethyl fumarate (diethyl maleate) (0.57 mmol), and 18ꢀcrownꢀ6
(10 mg) in dry CH3CN (8 mL). The reaction mixture was
refluxed at 80 °C for 18—26 h. Then water (20 mL) was added.
The reaction solution was extracted with ethyl acetate, and the
extract was washed with water (100 mL), dried over Na2SO4,
and concentrated. A darkꢀbrown oil was obtained. The comꢀ
pounds were separated by column chromatography on silica gel
60 (0.40–0.063 mm; 230—400 mesh) by successive elution. Paleꢀ
yellow crystals of dialkyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ2,3ꢀdicarboxyꢀ
lates 12a—c or 13a—c were isolated by elution with dichloroꢀ
methane; brightꢀyellow crystals of dialkyl 6ꢀRꢀ7ꢀphenylsulfonylꢀ
quinolineꢀ2,3ꢀdicarboxylate Nꢀoxides 10a—c or 11a—c, by
elution with a 1 : 8 ethyl acetate—dichloromethane mixture.
The elution with a 2 : 8 ethyl acetate—dichloromethane mixture
afforded yellow crystals of dialkyl 6ꢀRꢀ7ꢀfluoroquinolineꢀ
2,3ꢀdicarboxylate Nꢀoxides 8a—c (or 9a—c). The characteristics
of compounds 8a—c—13a—c are given in Tables 1—6.
The Xꢀray diffraction study of one of the compounds
(10a) confirmed the ipso substitution of the fluorine atom
at the C(7) atom by the phenylsulfonyl group (Fig. 1).
To summarize, we developed procedures for the
synthesis of the previously unavailable fluorineꢀconꢀ
taining quinolines based on 3ꢀfluoroꢀ4ꢀRꢀ6ꢀphenylsulꢀ
fonylmethylnitrobenzenes as products of vicarious
nucleophilic substitution of hydrogen in 4ꢀRꢀ3ꢀfluorineꢀ
containing nitroarenes with the chloromethyl phenyl
sulfone anion.
C(20)
O(6)
C(11)
C(19)
O(5)
O(3)
O(7)
C(12)
C(8)
O(1)
C(2)
C(9)
N(1)
C(15)
C(18)
C(7)
C(3)
C(4)
C(1)
S(1)
C(14)
C(16)
C(5)
C(6)
O(2)
O(8)
O(4)
C(17)
The Xꢀray diffraction data for compound 10a were collected
on a Xcalibur 3 diffractometer equipped with a CCD detector at
293 K (λ = 0.71073 Å, graphite monochromator) from a single
Fig. 1. Structure of dimethyl 6ꢀmethoxyꢀ7ꢀphenylsulfonylꢀ
quinolineꢀ2,3ꢀcarboxylate Nꢀoxide 10a.

Fluorinated 2,3ꢀdimethyl(diethyl) quinolinecarboxylates Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Table 2. Massꢀspectrometric and 1H NMR spectroscopic (DMSOꢀd6) data for compounds 8a—c and 9a—c
173
Comꢀ
pound
MS
m/z (Irel (%))
1H NMR
δ (J/Hz)
8а
309 [М]+ (63), 293 [М – O]+(31), 262 [М – O – OMe]+
(42), 231 [М – O – OMe – OMe]+ (36), 200 [М – O –
– OMe – OMe – OMe]+ (27), 172 [М – O – OMe –
– OMe – OMe – CO]+ (59), 144 [М – O – OMe –
– OMe – OMe – CO – CO]
3.92 (s, 6 H, (МеOOC)2); 4.23 (s, 3 H, МеO);
7.65 (d, 1 H, H(5), 4JH,F = 9.2); 7.84 (d, 1 H, H(8),
3JH,F = 12.8); 8.89 (s, 1 H, H(4), CH)
8b
323 [М]+ (58), 307 [М – O]+ (47), 276 [М – O –
– OMe]+ (35), 245 [М – O – OMe – OMe]+ (29),
217 [М – O – OMe – OMe – CO]+ (27), 189
[М – O – OMe – OMe – CO – CO] (61)
1.62 (t, 3 H, МеCH2O, 3JH,CH2 = 7.1); 3.89
(s, 6 H, (МеOOC)2); 4.91 (q, 2 H, МеCH2O,
3JH,CH = 7.2); 7.62 (d, 1 H, H(5), 4JH,F = 9.5);
7.80 (d3, 1 H, H(8), 3JH,F = 12.3); 8.82 (s, 1 H,
H(4), CH)
8c
9a
364 [М]+ (100), 348 [М – O]+ (35), 317 [М – O – OMe]+
(62), 303 [М – O – OMe – OMe]+ (35), 289 [М – O –
– OMe – OMe – N]+ (36), 259 [М – O – OMe – OMe –
N – OMeCH2]+ (98)
337 [М]+ (83), 321 [М – O]+ (69), 292 [М – O –
– MeCH2]– (41), 263 [М – O – MeCH2 – MeCH2]+ (35),
219 [М – O – MeCH2 – MeCH2 – COO]+ (39)
3.24 (m, 4 H, N(CH2)2); 3.80 (m, 4 H, O(CH2)2);
4.08 (s, 6 H, (МеOOC)2); 7.64 (d, 1 H, H(5),
4JH,F = 8.8); 8.20 (d, 1 H, H(8), 3JH,F = 13.4);
8.60 (s, 1 H, H(4), CH)
1.42 (t, 6 H, (МеCH2OOC)2, 3JH,CH = 7.0);
4.02 (s, 3 H, МеO); 4.54 (q, 4 H, (М2еCH2OOC)2,
3JH,CH = 7.2); 7.20 (d, 1 H, H(5), 4JH,F = 9.6);
8.24 (d3, 1 H, H(8), 3JH,F = 11.6); 8.72 (s, 1 H,
H(4), CH)
9b
9c
351 [М]+ (53), 335 [М – O]+ (67), 306 [М – O –
– MeCH2]+ (29), 277 [М – O – MeCH2 – MeCH2]+ (35),
233 [М – O – MeCH2 – MeCH2 – COO]+ (31),
189 [М – O – Me CH2 – MeCH2 – COO – COO]– (57)
1.41 (t, 3 H, МеCH2O, 3JH,CH = 7.0); 1.46 (t, 6 H,
(МеCH2OOC)2, JH,CH = 7.12); 4.78 (q, 2 H, МеCH2O,
3
2
3JH,CH = 7.2); 4.79 (q, 4 H, (МеCH2OOC)2, 3JH,CH
=
3
3
7.3); 6.73 (d, 1 H, H(5), 4JH,F = 8.7); 7.23 (d, 1 H,
H(8), 3JH,F = 11.9); 8.39 (s, 1 H, H(4), CH)
392 [М]+ (68), 376 [М – O]+ (39), 347 [М – O –
– MeCH2]+ (26), 318 [М – O – MeCH2 – MeCH2]+ (33),
274 [М – O – MeCH2 – MeCH2 – COO]+ (18),
230 [М – O – MeCH2 – MeCH2 – COO – COO]+ (29)
1.50 (t, 6 H, (МеCH2OOC)2, 3JH,CH2 = 7.0); 3.20
(m, 4 H, N(CH2)2); 4.00 (m, 4 H, O(CH2)2); 4.60
(q, 4 H, (МеCH2OOC)2, 3JH,CH3 = 7.2); 7.74 (d, 1 H,
H(5), 4JH,F = 8.9); 8.14 (d, 1 H, H(8), 3JH,F = 13.4);
8.47 (s, 1 H, H(4), CH)
Table 3. Reaction conditions, yields, melting points, and elemental analysis data for compounds 10a—c and 11a—c
Comꢀ
pound
Т/°С
τ/h
Yield
(%)
M.p./°С
Rf*
М
Found
Calculated
Molecular
formula
(%)
C
N
H
10a
10b
10c
11a
11b
11c
80
80
80
80
80
80
24
24
18
26
26
20
40
38
35
38
36
40
246—247
234—235
241—242
176—177
145—146
183—184
0.46
0.40
0.44
0.55
0.38
0.38
431.42
445.45
486.25
459.49
473.51
514.56
55.60
55.68
56.59
56.62
56.78
56.78
57.47
57.51
58.30
58.34
58.30
58.35
3.90
3.97
4.27
4.30
4.50
4.55
4.59
4.61
4.80
4.89
4.98
5.09
3.20
3.24
3.10
3.14
5.70
5.75
2.98
3.05
2.89
2.95
5.40
5.44
C20H17NSO8
C21H19NSO8
C23H22N2SO8
C22H21NSO8
C23H23NSO8
C25H26N2SO8
* A 1 : 8 ethyl acetate—dichloromethane mixture as the eluent.
crystal of dimensions 5Ѕ6Ѕ9 mm3, the orthorhombic system,
space group Pbca, the unit cell parameters a = 8.8140(10) Å,
b = 16.186(2) Å, c = 27.356(3) Å, α = β = γ = 90 °C, Z = 8,
F(000) = 899. A total of 12378 reflections were measured, of
which 3909 reflections were independent (Rint = 0.0830). The
absorption correction was not applied because the absorption
coefficient was small (μ = 0.101 mm–1). The structure was
solved by direct methods and refined by the fullꢀmatrix leastꢀ

174
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Kotovskaya et al.
Table 4. Massꢀspectrometric and 1H NMR spectroscopic (DMSOꢀd6) data for compounds 10a—c and 11a—c
Comꢀ
pound
MS
m/z (Irel (%))
1H NMR
δ (J/Hz)
10а
431 [М]+ (63), 415 [М – O]+ (20), 384 [М – O – OMe]+
(100), 356 [М – O – OMe – CO]– (75), 326 [М – O –
– OMe – CO – CO]+ (30)
3.86 (s, 3 H, МеO); 3.91 (s, 3 H, МеOOC);
3.97 (s, 3 H, МеOOC); 7.56—7.72 (m, 3 H, Ph);
7.96—7.99 (m, 2 H, Ph); 7.91 (s, 1 H, H(5));
8.51 (s, 1 H, H(4)); 9.15 (s, 1 H, H(8))
10b
445 [М]+ (36), 429 [М – O]+ (16), 398 [М – O – OMe]+
(44), 370 [М – O – OMe – OMe]+ (40), 342 [М – O –
– OMe – OMe – CO]+1 (31), 312 [М – O – OMe –
– OMe – CO – CO]+ (22), 285 [М – O – OMe – OMe –
– CO – CO – OMeCH2]+ (100)
1.38 (t, 3 H, МеCH2O, 3JH,CH2 = 7.0); 3.91
(s, 3 H, МеOOC); 4.10 (s, 3 H, МеOOC); 4.20
(q, 2 H, МеCH2O, 3JH,CH3 = 7.1); 7.32—7.79
(m, 3 H, Ph); 8.00—8.21 (m, 2 H, Ph); 7.90 (s, 1 H,
H(5)); 8.56 (s, 1 H, H(4)); 9.24 (s, 1 H, H(8))
10c
11a
11b
486 [М]+ (18), 470 [М – O]+ (6), 439 [М – O – OMe]+
(35), 411 [М – O – OMe – OMe]+ (16), 380 [М – O –
– OMe – OMeCOO]+ (27), 352 [М – O – OMe –
– OMeCO – CO]+ (20), 338 [М – O – OMe – OMeCO–
– CO – N]+ (9)
459 [М]+ (10), 443 [М – O]+ (7), 412 [М – O – OMe]+
(4), 383 [М – O – OMe – MeCH2]+ (35), 354 [М –
– O – OMe – MeCH2 – MeCH2]+ (88), 310 [М – O –
– OMe – MeCH2 – MeCH2 – COO]+ (13), 266 [М –
– O – OMe – MeCH2 – MeCH2 – COO – COO]+ (29)
473 [М]+ (10), 457 [М – O]+ (13), 428 [М – O –
– MeCH2]+ (4), 399 [М – O – MeCH2 – MeCH2]+ (33),
355 [М – O – MeCH2 – MeCH2 – COO]– (68),
311 [М – O – MeCH2 – MeCH2 – COO – COO]–
(32), 282 [М – O – MeCH2 – MeCH2 – COO –
– COO – MeCH2]+ (2)
3.10 (m, 4 H, N(CH2)2); 3.59 (m, 4 H, O(CH2)2);
3.95 (s, 3 H, МеOOC); 3.40 (s, 3 H, МеOOC);
7.60—7.73 (m, 3 H, Ph); 7.98—8.00 (m, 2 H, Ph);
8.02 (s, 1 H, H(5)); 8.57 (s, 1 H, H(4));
9.18 (s, 1 H, H(8))
1.39 (t, 6 H, (МеCH2OOC)2, 3JH,CH = 7.0); 3.91
(s, 3 H, МеO); 4.42 (q, 4 H, (МеCH22O)2,
3JH,CH2 = 7.0); 7.58—7.71 (m, 3 H, Ph); 7.95—7.97
(m, 2 H, Ph); 8.00 (s, 1 H, H(5)); 8.52 (s, 1 H, H(4));
9.15 (s, 1 H, H(8))
1.31 (t, 6 H, (МеCH2OOC)2, 3JH,CH2 = 7.0); 1.40
(t, 3 H, МеCH2O, 3JH,CH2 = 7.1); 4.17 (q, 2 H,
МеCH2O, 3JH,CH = 7.1); 4.30 (q, 4 H, (МеCH2OOC)2,
3
3JH,CH3 = 7.2); 7.56—7.70 (m, 3 H, Ph); 7.95—7.98
(m, 2 H, Ph); 7.89 (s, 1 H, H (5)); 8.59 (s, 1 H, H(4));
9.20 (s, 1 H, H (8))
11c
514 [М]+ (26), 498 [М – O]+ (30), 469 [М – O –
1.40 (t, 6 H, (МеCH2OOC)2, 3JH,CH2 = 7.0); 2.80
– MeCH2]+ (18), 440 [М – O – MeCH2 – MeCH2]+ (24), (m, 4 H, N(CH2)2); 3.59 (m, 4 H, O(CH2)2); 4.43
396 [М – O – MeCH2 – MeCH2 – COO]+ (63), 352
[М – O – MeCH2 – MeCH2 – COO – COO]+ (43)
(q, 4 H (МеCH2OOC)2, JH,CH3 = 7.2); 7.53—7.64
(m, 3 H, Ph); 7.87—7.90 (m, 2 H, Ph); 8.29 (s, 1 H,
H (5)); 8.56 (s, 1 H, H(4)); 9.29 (s, 1 H, H (8))
3
Table 5. Reaction conditions, yields, melting points, and elemental analysis data for compounds 12a—c and 13a—c
Comꢀ
pound
Т/°С
τ/h
Yield
(%)
M.p.
/°С
Rf*
M
Found
Calculated
Molecular
formula
(%)
C
H
N
12a
12b
12c
13a
13b
13c
80
80
80
80
80
80
24
24
18
26
26
20
25
27
30
23
25
28
176—178
186—188
176—178
168—170
173—174
212—213
0.73
0.70
0.68
0.70
0.69
0.70
293.27
307.29
348.33
321.33
335.36
376.41
57.30
57.33
58.59
58.62
58.57
58.61
59.76
59.80
60.80
60.88
60.59
60.62
4.29
4.33
4.56
4.60
4.89
4.93
4.97
5.03
5.38
5.42
5.58
5.63
4.70
4.77
4.50
4.56
7.98
8.03
4.30
4.36
4.12
4.17
7.39
7.44
C14H12FNO5
C15H14FNO5
C17H17FN2O5
C16H16FNO5
C17H18FNO5
C19H21FN2O
* Dichloromethane as the eluent.
We thank P. A. Slepukhin (I. Ya. Postovsky Institute
squares method with anisotropic displacement parameters
for nonꢀhydrogen atoms (isotropically for H atoms) using
the SHELXLꢀ97 program package.23 The final R factors were
R = 0.0497, wR2 = 0.0516 (I > 2σ(I)), GOOF = 1.006.
of Organic Synthesis of the Ural Branch of the Russian
Academy of Sciences) for performing the Xꢀray diffracꢀ
tion study.

Fluorinated 2,3ꢀdimethyl(diethyl) quinolinecarboxylates Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
175
1
Table 6. Massꢀspectrometric and H NMR spectroscopic (DMSOꢀd6) data for compounds 12a—c and 13a—c
Comꢀ
pound
MS
m/z (Irel (%))
1H NMR
δ (J/Hz)
12a
12b
12c
13a
13b
293 [М]+ (35), 262 [М – OMe]+ (20), 234 [М –
– OMe – CO]+ (31), 206 [М – OMe – CO – CO] (30),
175 [М – OMe – CO – CO – OMe]+ (100), 161
[М – OMe – CO – CO – OMe – N]+ (4)
307 [М]+ (35), 276 [М – OMe]+ (15), 245 [М –
– OMe – OMe]+ (18), 217 [М – OMe – OMe – CO]+
(20), 189 [М – OMe – OMe – CO – CO]+ (76), 160
[М – OMe – OMe – CO – CO – MeCH2]+ (8)
348 [М]+ (100), 317 [М – OMe]+ (12), 286 [М –
– OMe – OMe]– (19), 258 [М – OMe – OMe – CO]–
(10), 230 [М – OMe – OMe – CO – CO]+ (20),
216 [М – OMe – OMe – CO – CO – N]+ (23)
321 [М]+ (46), 292 [М – MeCH2]+ (15), 263
[М – MeCH2 – MeCH2]+ (30), 219 [М – MeCH2 –
– MeCH2 – COO]+ (16), 175 [М – MeCH2 – MeCH2 –
– COO – COO]+ (45)
3.80 (s, 6 H, (МеOOC)2); 4.18 (s, 3 H, МеO),
7.60 (d, 1 H, H(5), 4JH,F = 8.9); 7.80 (d, 1 H,
H(8), 3JH,F = 11.8); 8.82 (s, 1 H, H(4), CH)
1.50 (t, 3 H, МеCH2O, 3JH,CH2 = 7.0); 3.80 (s, 6 H,
(МеOOC)2); 4.80 (q, 2 H, MeCH2O, 3JH,CH3 = 7.2);
7.60 (d, 1 H, H(5), 4JH,F = 8.5); 7.81 (d, 1 H,
H(8), 3JH,F = 11.3); 8.82 (s, 1 H, H(4), CH)
3.20 (m, 4 H, N(CH2)2); 3.80 (m, 4 H,
O(CH2)2); 4.00 (s, 6 H, (МеOOC)2); 7.58
(d, 1 H, H(5), 4JH,F = 9.5); 7.80 (d, 1 H, H(8),
3JH,F = 13.7); 8.80 (s, 1 H, H(4), CH)
1.37 (t, 6 H, (МеCH2OOC)2, 3JH,CH2 = 7.1); 3.94
(s, 3 H, МеO), 4.46 (q, 4 H, (МеCH2OOC)2,
3JH,CH = 7.2); 7.62 (d, 1 H, H(5), 4JH,F = 8.6);
3
7.90 (d, 1 H, H(8), 3JH,F = 11.0); 8.80 (s, 1 H, H(4), CH)
335 [М]+ (30), 306 [М – MeCH2]+ (18), 277
[М – MeCH2 – MeCH2]+ (23), 249 [М – MeCH2 –
– MeCH2]+ (41), 220 [М]+ (52), 192 [М]+ (63)
1.36 (t, 3 H, МеCH2O, 3JH,CH2 = 7.0); 1.42 (t, 6 H,
(МеCH2OOC)2, 3JH,CH2 = 7.1); 4.70 (q, 2 H,
МеCH2O, 3JH,CH = 7.2); 4.76 (q, 4 H, (МеCH2OOC)2,
3
3JH,CH = 7.3); 7.64 (d, 1 H, H(5), 4JH,F = 8.7); 7.92
3
(d, 1 H, H(8), 3JH,F = 10.9); 8.82 (s, 1 H, H(4), CH)
13c
376 [М]+ (100), 347 [М]+ (18), 318 [М]+ (21),
290 [М]+ (10), 262 [М]+ (26), 233 [М]+ (35),
205 [М]+ (46)
1.30 (t, 6 H, (МеCH2OOC)2, 3JH,CH2 = 7.1); 3.18
(m, 4 H, N(CH2)2); 3.64 (m, 4 H, O(CH2)2); 4.38
(q, 4 H, (МеCH2OOC)2, 3JH,CH3 = 7.3); 7.37 (d, 1 H,
H(5), 4JH,F = 9.3); 7.64 (d, 1 H, H(8), 3JH,F = 11.9);
8.81 (s, 1 H, H(4), CH)
10. W.O. 0034,265, Al., Chem. Abstrs, 2000, 133, 43453g.
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This study was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ12112),
the Council on Grants of the President of the Russian
Federation (Program for State Support of Leading Scientific
Schools of the Russian Federation, Grant NShꢀ3758.2008.3),
and the US Civilian Research and Development Foundaꢀ
tion (CRDF, Program BRHE, Grant CRDF BP 2M05).
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Received April 7, 2008;
in revised form July 16, 2008