Preparation of fluorine-containing exo- and endocyclic enamine derivatives of 2-acylcyclopentane-1,3-diones

Article abstract of DOI:10.1134/S1070363214030098

The interaction of aromatic amines (4-fluorinebenzylamine, 3-trifluoromethylbenzylamine, 4-fluoroaniline, or 3,4-difluoroaniline) with either 2-acylcyclopentane-1,3-diones (fluorine-substituted or fluorine-free) or their enol derivatives (chlorovinyldiket

Full text of DOI:10.1134/S1070363214030098

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 3, pp. 465–473. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © T.S. Khlebnikova, Yu.A. Piven’, F.A. Lakhvich, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 3, pp. 407–415.
Preparation of Fluorine-containing
Exo- and Endocyclic Enamine Derivatives
of 2-Acylcyclopentane-1,3-diones
T. S. Khlebnikova, Yu. A. Piven’, and F. A. Lakhvich
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus,
ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus
e-mail: khlebnicova@iboch.bas-net.by
Received April 18, 2013
Abstract―The interaction of aromatic amines (4-fluorinebenzylamine, 3-trifluoromethylbenzylamine, 4-
fluoroaniline, or 3,4-difluoroaniline) with either 2-acylcyclopentane-1,3-diones (fluorine-substituted or
fluorine-free) or their enol derivatives (chlorovinyldiketones) has led to fluorine-containing exo- or endocyclic
enamine derivatives of 2-acylcyclopentane-1,3-diones.
DOI: 10.1134/S1070363214030098
Organofluorine compounds are attractive due to
numerous applications in pharmaceutics, agricultural
chemistry, and material science [1−5]. The recently
emerging trend is incorporation of fluorine atoms into
natural as well as synthetic biologically active
compounds in order to enhance their lipophilicity and
biological accessibility [6, 7]. Triacylmethane
fragment is found in many natural compounds produced
by various plants, microbes, insects, and in their
synthetic derivatives; such compounds are used as
drugs and modern plant protectants [8−11]. The
presence of β-tricarbonyl moiety leads to high
reactivity of 2-acylcyclopentane-1,3-diones (both
natural and synthetic) and thus opens vast possibilities
towards their chemical transformation into physiolo-
gically active compounds of various classes [12−14].
Enamine derivatives of 2-acylcyclopentane-1,3-diones,
depending on the cycle and the side chain structure,
reveal antibacterial, herbicide, antiinflammatory,
antiaggregatory, anti-ischemic, and gastroprotective
activity [15−19].
aluminum chloride [20] or acetone cyanohydrin [21];
β-triketones containing perfluoroalkanoyl groups can
be prepared by acylation of cyclopentane-1,3-dione
with perfluorocarboxylic acids in the presence of
imidazole in chloroform [22].
O–С-Isomerization of enol acylates Ia–Ih in the
presence of triethylamine with acetone cyanohydrin as
catalyst gave the corresponding 2-acylcyclopentane-
1,3-diones IIa–IIh containing various acyl side groups
(acetyl, propanoyl, cyclopropanoyl, furanoyl, benzoyl,
fluorobenzoyl, or fluorophenylacetyl) in 61–89%
yields (Scheme 1). With anhydrous aluminum chloride
as catalyst the target products were obtained in a lower
yield due to sensitivity of the catalyst to moisture and
the necessity to work up the products in strongly acid
medium; in some cases the mixture of products was
obtained inseparable by chromatography. Enol acylates
Ia–Ih were prepared following a known procedure
[20], via О-acylation of cyclopentane-1,3-dione with
the corresponding acyl chlorides in chloroform in the
presence of pyridine.
This work aimed at preparation of new fluorine-
containing exo- and endocyclic enamine derivatives of
2-acylcyclopentane-1,3-diones.
Cyclopentane-type β-triketones existing in the enol
form could participate in various chemical trans-
formations involving different active sites of the
molecule, including exo- and endocyclic carbonyls.
The interaction of fluorinated 2-acylcyclopentane-1,3-
diones (as well as their fluorine-free analogs) with
fluorine-substituted compounds led to the fluorine-
The most common and efficient method of
preparation of fluorine-free cyclopentane-type β-
triketones is О–С-isomerization of cyclopentane-1,3-
dione enol acylates under the action of anhydrous
465

466
KHLEBNIKOVA et al.
Scheme 1.
O
O
O
O
Me
Me
CN
OH
R1COCl
R1
O
O
O
O
R1
Iа_Ih
IIа_IIh
O
NHR2
R1
1 equiv. R2NH2
O
IIIа_IIIp
O
O
O
O
2 equiv. R2NH2
R1
R1
(COCl)2
NHR2
Vа_Vm
Cl
IVа_IVh
I, II, IV, R1 = Me (a), Et (b), cyclopropyl (c), furan-2-yl (d), Ph (e), 2-FC6H4 (f), 3-FC6H4 (g); 4-FC6H4CH2 (h); III, R1 =
Me: R2 = 4-FC6H4 (a), 4-FC6H4CH2 (b); R1 = Et: R2 = 4-FC6H4 (c), 4-FC6H4CH2 (d); R1 = cyclopropyl: R2 = 4-FC6H4 (e), 4-
FC6H4CH2 (f); R1 = furan-2-yl: R2 = 4-FC6H4 (g), 4-FC6H4CH2 (h); R1 = Ph: R2 = 4-FC6H4 (i), 4-FC6H4CH2 (j); R1 = 2-
FC6H4, R2 = 4-FC6H4CH2 (k); R1 = 3-FC6H4: R2 = 4-FC6H4 (l), 4-FC6H4CH2 (m); R1 = 4-FC6H4CH2: R2 = 4-FC6H4 (n), 4-
FC6H4CH2 (o), 3-CF3C6H4CH2 (p); V, R1 = Me, R2 = 4-FC6H4 (a); R1 = Et, R2 = 4-FC6H4 (b); R1 = cyclopropyl: R2 = 4-
FC6H4 (c), 4-FC6H4CH2 (d); R1 = furan-2-yl: R2 = 4-FC6H4 (e), 4-FC6H4CH2 (f); R1 = Ph: R2 = 4-FC6H4 (g), 4-FC6H4CH2 (h);
R1 = 3-FC6H4, R2 = 4-FC6H4CH2 (i); R1 = 4-FC6H4CH2: R2 = 4-FC6H4 (j), 4-FC6H4CH2 (k), 3,4-F2C6H3 (l), 3-CF3C6H4CH2 (m).
containing products, potentially bioactive agents. In
view of that, in this work the 2-acylcyclopentane-1,3-
diones IIa–IIh were introduced into the reactions with
primary amines fluorinated at their aromatic
substituents. In particular, exocyclic enamino-
diketones IIIa–IIIp were prepared by condensation of
triketones IIa–IIh with fluoroaromatic amines (4-
fluoroaniline, 3,4-difluoroaniline, 4-fluorobenzyl-
amine, or 3-trifluoromethylbenzylamine) upon boiling
the equimolar amounts of the reagents in benzene for
4 h (4-fluorobenzylamine or 3-trifluoromethyl-benzyl-
amine) or for 30 h (4-fluoroaniline or 3,4-difluoro-
aniline). The reactions proceeded with high
regioselectivity at carbonyl of the side acyl chain to
give the corresponding enamine derivatives IIIa–IIIp
with yields of 50–83%. It is known that, in contrast to
cyclic β-triketones, their enol derivatives (chlorovinyl-
diketones and enol esters) react with amines via vinyl
substitution to give the endocyclic enaminodiketones
[12]. Therefore, in order to change the site of the
nucleophilic attack, cyclopentane-type triketones IIa–
IIh were converted into chlorovinyldiketones IVa–
IVh by treatment with oxalyl chloride. Being unstable,
the chlorovinyldiketones were introduced without
isolation into the reaction with double amount of the
above-listed aromatic amines. The amination was
performed at room temperature in chloroform for
2 h, the target endocyclic enamine derivatives Va–Vm
were isolated by column chromatography in yields of
54–78%. Parent chlorovinyldiketones IVb–IVh were
prepared by treating the corresponding triketones with
10-fold excess of oxalyl chloride at room temperature
during 10–30 min; compound IVa was obtained by
refluxing triketone IIa in anhydrous chloroform with
5-fold excess of oxalyl chloride during 2.5 h followed by
removal of the excess of oxalyl chloride and chloroform.
Structures of the prepared products were confirmed
by elemental analysis, IR, 1Н NMR, 13С NMR, and 19F
NMR spectroscopy (see table). IR spectra of
compounds IIIa–IIIp contained three characteristic
absorption bands assigned to the double bond (1560–
1600 cm–1) and to two conjugated endocyclic carbonyl
1
bonds (1610–1640 and 1660–1690 cm–1). In the Н
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467
IR, 1Н NMR, 13С NMR, and 19F NMR spectra of compounds IIIa–IIIp and Va–Vm
19F NMR
spectrum,
δF, ppm
Comp. IR spectrum,
no.
1Н NMR spectrum, δ, ppm (J, Hz)
13С NMR spectrum, δC, ppm (JCF, Hz)
ν, cm–1
1685, 1630, 2.52–2.55 m (2H, CH2cyclopent), 2.53 m (3H, CH3), 16.0, 32.9, 34.5, 107.5, 116.7 d (J 23), 127.5 d −112.7
1610, 1580 2.59–2.62 m (2H, CH2cyclopent), 7.16–7.18 m (4H, (J 9), 131.6 (J 2), 162.0 d (J 249), 169.6, 202.8,
IIIa
Harom), 13.31 br.s (1H, NH)
206.6
1675, 1620, 2.46–2.53 m (4H, 2CH2cyclopent), 2.62 s (3H, CH3), 4.59 14.3, 32.7, 34.2, 46.1, 107.0, 116.3 d (J 22), −113.6
1605, 1580 d (2H, CH2, J 6.0), 7.07–7.10 m (2H, Harom), 7.23– 128.9 d (J 8), 130.8 d (J 2) 162.6 d (J 248),
IIIb
IIIc
7.26 m (2H, Harom), 12.20 br.s (1H, NH)
170.8, 202.8, 206.5
1680, 1620, 1.13 t (3H, CH3, J 7.4), 2.47–2.51 m (2H, CH2cyclopent), 12.5, 21.5, 33.0, 34.2, 106.2, 116.7 d (J 23), −112.6
1605, 1570 2.56–2.58 m (2H, CH2cyclopent), 2.85 q (2H, CH2, J 127.8 d (J 8), 131.5 d (J 2), 162.1 d (J 249),
7.4), 7.13–7.18 m (4H, Harom), 13.26 br.s (1H, NH)
175.2, 201.9, 207.3
1670, 1610, 1.20 t (3H, CH3, J 7.6), 2.46–2.48 m (2H, CH2cyclopent), 11.6, 20.7, 32.8, 34.1, 45.6, 105.8, 116.3 d (J −113.6
1595, 1570 2.51–2.54 m (2H, CH2cyclopent), 3.07 q (2H, CH2, J 22), 129.0 d (J 8), 131.1 d (J 2), 162.7 d (J 247),
7.6), 4.62 d (CH2, CH2, J 6.1), 7.07–7.10 m (2H, 175.4, 201.9, 207.1
IIId
Harom), 7.25–7.28 m (2H, Harom), 12.19 br.s (1H, NH)
1660, 1605, 0.55–0.58 m (2H, CH2cycloprop), 1.07–1.11 m (2H, 11.2, 12.9, 33.6, 109.1, 116.3 d (J 23), 126.6 d −113.6
IIIe
IIIf
1575
CH2cycloprop), 2.25–2.31 m (1H, CHcycloprop), 2.56 s (J 8), 132.9 d (J 2), 151.5 d (J 248), 171.7,
(4H, 2CH2cyclopent), 7.11–7.14 m (2H, Harom), 7.21– 201.3
7.24 m (2H, Harom), 13.63 br.s (1H, NH)
1680, 1605, 0.88–0.91 m (2Н, CH2cycloprop), 1.26–1.30 m (2Н, 9.3, 11.2, 33.5, 47.5, 107.9, 116.2 d (J 22), −113.8
1575
CH2cycloprop), 1.91–1.97 m (1Н, CHcycloprop), 2.49 s 128.9 d (J 8), 131.4 d (J 3), 162.5 d (J 247),
(4Н, 2СН2cyclopent), 4.79 d (2Н, CH2, J 6.0), 7.06–7.10 173.3, 203.8
m (2Н, Нarom), 7.25–7.28 m (2Н, Нarom), 12.41 br.s
(1Н, NH)
1680, 1610, 2.57–2.66 m (4Н, 2СН2cyclopent), 6.55–6.56 m (1Н, 33.1, 34.1, 105.8, 112.3, 116.0 d (J 23), 121.8, −114.7
IIIg
IIIh
1580, 1570,
1555
Нfuranоил), 6.83–6.85 m (2Н, Нarom), 6.97–7.00 m (2Н, 125.5 d (J 8), 134.6 d (J 2),141.6, 145.6, 152.8,
Нarom), 7.37 d (1Н, Нfuran, J 1.0), 7.42 d (1Н, Нfuran, J 161.0 d (J 248), 200.0, 207.5
3.3), 13.50 br.s (1Н, NH)
1665, 1610, 2.53 s (4Н, 2СН2cyclopent), 4.70 d (2Н, CH2, J 5.9), 33.3, 49.3, 105.3, 112.2, 116.0 d (J 22), 121.5, −113.9
1580, 1570, 6.63–6.64 m (1Н, Нfuran), 7.04–7.07 m (2Н, Нarom), 129.2 d (J 8), 131.8 d (J 2), 141.9, 145.8, 155.8,
1555
7.24–7.27 m (2Н, Нarom), 7.42 d (1Н, Нfuran, J 3.3), 162.5 d (J 247), 203.0
7.68 d (1Н, Нfuran, J 1.0), 12.50 br.s (1Н, NH)
1690, 1630, 2.49–2.51 m (2H, CH2cyclopent), 2.67–2.69 m (2H, 33.1, 34.2, 106.7, 116.1 d (J 22), 126.4 d (J 8), −114.2
1600, 1560 CH2cyclopent), 6.78–6.81 m (2H, Harom), 6.85–6.89 m 128.4, 128.6, 129.3, 130.6, 132.7 d (J 2), 160.1
(2H, Harom), 7.22–7.23 m (2H, Harom), 7.35–7.38 m d (J 249), 166.3, 200.3, 207.6
(2H, Harom), 7.42–7.45 m (1H, Harom), 13.55 br.s (1H,
IIIi
IIIj
NH)
1685, 1620, 2.40–2.43 m (2H, CH2cyclopent), 2.57–2.60 m (2H, 32.0, 34.0, 47.3, 106.5, 116.0 d (J 22), 127.1, −113.8
1560, 1550 CH2cyclopent), 4.36 d (2Н, CH2, J 6.3), 7.01–7.05 m 128.6, 129.0 d (J 8), 129.8, 130.4, 131.6 d (J 3),
(2H, Harom), 7.10–7.13 m (2H, Harom), 7.23–7.24 m 162.5 d (J 248), 169.2, 200.4, 207.2
(2H, Harom), 7.48–7.54 m (3H, Harom), 12.27 br.s (1H,
NH)
1690, 1630, 2.41–2.44 m (2H, CH2cyclopent), 2.57–2.60 m (2H, 33.1, 34.1, 47.7, 106.9, 116.2 d (J 22), 116.3 d −113.6,
IIIk
IIIl
1560
CH2cyclopent), 4.32 d.d (1H, CH2, J 15.2, 6.4), 4.42 d.d (J 21), 117.9 d (J 16), 124.7 d (J 3), 129.2 d (J −113.9
(1H, CH2, J 15.2, 6.0), 7.01–7.04 m (2H, Harom), 1), 129.4 d (J 8), 131.2 d (J 3), 132.7 d (J 8),
7.12–7.14 m (2H, Harom), 7.17−7.29 m (3H, Harom), 158.8 d (J 249), 162.7 d (J 248), 163.4, 200.3,
7.51–7.55 m (1H, Harom), 12.20 br.s (1H, NH)
207.0
1685, 1640, 2.50–2.53 m (2H, CH2cyclopent), 2.67–2.70 m (2H, 33.2, 34.3, 106.8, 116.1 d (J 23), 116.4 d −111.6,
1585, 1565 CH2cyclopent), 6.81–6.84 m (2H, Harom), 6.89−6.96 m (J 23), 117.8 d (J 21), 124.5 d (J 2), 126.6 (J 8), −113.7
(3H, Harom), 6.99–7.01 m (1H, Harom), 7.11–7.15 m 130.4 (J 8), 131.4 d (J 8), 132.5 (J 2), 161.2 d (J
(1H, Harom), 7.31–7.36 m (2H, Harom), 13.51 s (1H, 249), 162.5 d (J 248), 164.7, 200.4, 207.7
NH)
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KHLEBNIKOVA et al.
Table (Contd.)
19F NMR
13С NMR spectrum, δC, ppm (JCF, Hz) spectrum, δF,
ppm
Comp. IR spectrum,
no.
1Н NMR spectrum, δ, ppm (J, Hz)
ν, cm–1
1690, 1630, 2.41–2.44 m (2H, CH2cyclopent), 2.57–2.60 m (2H, CH2cyclopent), 33.1, 34.1, 47.5, 106.5, 114.7 d (J 24),
−111.1,
−113.5
IIIm
1560
4.34 d (2H, CH2, J 6.3), 6.93–6.95 m (1H, Harom), 116.3 d (J 22), 117.6 d (J 21), 122.9 d
7.00−7.06 m (3H, Harom), 7.09–7.12 m (2H, Harom), (J 2), 129.1 d (J 8), 130.9 d (J 8), 131.4 d
7.20–7.24 m (1H, Harom), 7.45–7.49 m (1H, Harom), (J 3), 131.8 d (J 8), 162.7 d (J 247), 162.8
12.22 br.s (1H, NH)
d (J 249), 167.8, 200.5, 207.3
1685, 1620, 2.57–2.60 m (2H, CH2cyclopent), 2.64–2.66 m (2H, CH2cyclopent), 31.9, 32.9, 34.4, 107.1, 115.5 d (J 21),
−112.1,
−115.7
IIIn
IIIo
IIIp
1555
4.37 s (2H, CH2), 6.84–6.90 m (4H, Harom), 6.97–7.00 m 116.5 d (J 23), 128.1 d (J 9), 130.0 d
(2H, Harom), 7.05–7.08 m (2H, Harom), 13.32 br.s (1H, (J 8), 131.0 d (J 2), 131.4 d (J 2), 161.8 d
NH)
(J 246), 162.3 d (J 250), 170.3, 202.2,
207.4
1685, 1620, 2.52–2.58 m (4H, 2СH2cyclopent), 4.50 d (2H, CH2, J 6.0), 31.5, 32.7, 34.3, 46.3, 106.8, 116.0 d
−113.4,
−115.3
1555
4.53 s (2H, CH2), 6.99−7.05 m (4H, Harom), 7.08–7.10 m (J 22), 116.2 d (J 22), 129.0 d (J 8), 129.9
(2H, Harom), 7.16–7.19 m (2H, Harom), 12.23 br.s (1H, d (J 8), 130.2 d (J 2), 130.6 d (J 2), 161.9
NH)
d (J 246), 162.6 d (J 248), 170.5, 202.3,
207.0
1680, 1620, 2.54–2.61 m (4H, CH2cyclopent), 4.54 s (2H, CH2), 4.59 d 31.5, 32.7, 34.3, 46.4, 107.0, 116.1 d −63.0 (CF3),
1570
(2H, CH2, J 6.2), 6.97–7.00 m (2H, Harom), 7.14–7.17 m (J 22), 123.6 q (J 273), 124.0 q (J 2),
(2H, Harom), 7.27–7.32 m (2H, Harom), 7.45–7.48 m (1H, 125.3 q (J 3), 129.8, 129.9 d (J 8), 130.0,
−115.2
Harom), 7.57–7.58 m (1H, Harom), 12.31 br.s (1H, NH)
130.3, 131.5 q (J 33), 135.9, 161.9 d (J
247), 170.7, 202.4, 207.2
1675, 1615, 2.44–2.47 m (2H, CH2cyclopent), 2.56 s (3H, CH3), 2.70– 25.3, 29.0, 33.8, 112.0, 116.8 d (J 23),
1580 2.72 m (2H, CH2cyclopent), 7.12–7.17 m (2H, Harom), 7.21– 126.4 d (J 9), 133.0 d (J 2), 161.5 d
7.24 m (2H, Harom), 11.94 br.s (1H, NH) (J 248), 180.5, 198.1, 200.2
−113.8
−114.0
Vа
1680, 1615, 1.13 t (3H, CH3, J 7.3), 2.44–2.46 m (2H, CH2cyclopent), 7.9, 25.3, 33.7, 34.2, 111.4, 116.7 d
Vb
1585
2.71–2.73 m (2H, CH2cyclopent), 3.01 q (2H, CH2, J 7.3), (J 23), 126.1 d (J 8), 133.1 d (J 2), 161.4
7.11–7.15 m (2H, Harom), 7.21–7.24 m (2H, Harom), d (J 248), 180.5, 200.0, 201.3
12.01 br.s (1H, NH)
1665, 1605, 0.97–0.99 m (2Н, CH2cycloprop), 1.12–1.14 m (2Н, 11.7, 17.3, 25.0, 33.9, 111.7, 116.6 d
−114.0
−113.8
−113.6
−113.7
Vc
Vd
Ve
Vf
1565
CH2cycloprop), 2.48–2.51 m (2Н, CH2cyclopent), 2.70–2.73 m (J 23), 126.1 d (J 9), 133.1 d (J 2), 161.3
(2Н, CH2cyclopent), 3.48–3.53 m (1Н, CHcycloprop), 7.10– d (J 248), 180.1, 200.2, 200.4
7.12 m (2Н, Нarom), 7.20–7.22 m (2Н, Нarom), 12.13 br.s
(1Н, NH)
1670, 1600, 0.90–0.94 m (2Н, CH2cycloprop), 1.05–1.07 m (2Н, 11.3, 17.1, 24.0, 33.8, 47.1, 111.1, 116.0
1585
CH2cycloprop), 2.48–2.51 m (2Н, CH2cyclopent), 2.68–2.71 m d (J 22), 128.9 d (J 8), 131.6 d (J 2),
(2Н, CH2cyclopent), 3.43–3.48 m (1Н, CHcycloprop), 4.52 d 162.5 d (J 247), 181.4, 199.7, 200.2
(2Н, CH2, J 6.2), 7.05–7.09 m (2Н, Нarom), 7.23–7.26 m
(2Н, Нarom), 10.74 br.s (1Н, NH)
1670, 1605, 2.51–2.53 m (2H, CH2cyclopent), 2.76–2.78 m (2H, 25.5, 33.6, 110.5, 112.1, 116.7 d (J 23),
1565
CH2cyclopent), 6.57–6.58 m (1H, Hfuran), 7.13–7.17 m (2H, 121.0, 126.5 d (J 9), 133.0 d (J 2), 146.6,
Harom), 7.25–7.28 m (2H, Harom), 7.65–7.66 m (1H, Hfuran), 151.8, 161.5 d (J 248), 177.8, 182.5,
8.25 d (1H, Hfuran, J 3.6), 12.41 br.s (1H, NH)
197.6
1685, 1610, 2.51–2.54 m (2H, CH2cyclopent), 2.76–2.79 m (2H, 24.6, 33.6, 47.4, 110.0, 112.1, 116.3 d
1575
CH2cyclopent), 4.59 d (2H, CH2, J 6.2), 6.53–6.55 m (1H, (J 22), 120.6, 129.0 d (J 22), 131.6 d
Hfuran), 7.06–7.10 m (2H, Harom), 7.27–7.30 m (2H, (J 3), 146.5, 151.9, 162.7 d (J 247),
H
arom), 7.61–7.62 m (1H, Hfuran), 8.26 d (1H, Hfuran, 177.7, 187.8, 197.7
J 3.6), 11.18 br.s (1H, NH)
1675, 1610, 2.48–2.51 m (2H, CH2cyclopent), 2.77–2.79 m (2H, CH2cyclopent), 25.4, 33.7, 111.0, 116.8 d (J 23), 126.4 d
−113.6
Vg
1575
7.14–7.17 m (2H, Harom), 7.26–7.29 m (2H, Harom), (J 9), 127.6, 128.9, 131.7, 133.0 d (J 2),
7.41–7.44 m (2H, Harom), 7.49–7.52 m (1H, Harom), 138.8, 161.5 d (J 248), 182.0, 193.7,
7.72–7.74 m (2H, Harom), 12.06 br.s (1H, NH)
198.2
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469
Table (Contd.)
19F NMR
spectrum, δF,
ppm
Comp. IR spectrum,
no.
1Н NMR spectrum, δ, ppm (J, Hz)
13С NMR spectrum, δC, ppm (JCF, Hz)
ν, cm–1
1685, 1610, 2.49–2.52 m (2H, CH2cyclopent), 2.77–2.80 m (2H, 24.4, 33.5, 47.2, 110.3, 116.2 d (J 22),
−113.7
Vh
1575
CH2cyclopent), 4.61 d (2H, CH2, J 6.3), 7.08–7.11 m (2H, 127.5, 128.8, 129.0 d (J 8), 131.4, 131.5 d
Harom), 7.28–7.31 m (2H, Harom), 7.38–7.41 m (2H, (J 2), 138.9, 162.6 d (J 248), 183.1, 193.3,
Harom), 7.46–7.49 m (1H, Harom), 7.67–7.69 m (2H, 198.0
Harom), 10.77 br.s (1H, NH)
1685, 1610, 2.49–2.52 m (2H, CH2cyclopent), 2.78–2.81 m (2H, 24.5, 33.6, 47.4, 110.2, 115.8 d (J 23),
1600, 1585, CH2cyclopent), 4.61 d (2H, CH2, J 6.2), 7.08–7.12 m (2H, 116.4 d (J 22), 118.3 d (J 21), 124.6,
−113.5,
−114.1
Vi
Vj
Vk
Vl
1565
Harom), 7.14–7.18 m (1H, Harom), 7.28–7.31 m (2H, 129.1 d (J 8), 129.2, 131.4 d (J 2), 141.1 d
arom), 7.33–7.37 m (2H, Harom), 7.46–7.47 m (1H, (J 6), 162.2 d (J 246), 162.7 d (J 248),
Harom), 10.72 br.s (1H, NH) 183.3, 191.8, 198.0
H
1675, 1620, 2.48–2.50 m (2H, CH2cyclopent), 2.71–2.72 m (2H, 25.3, 33.8, 45.6, 110.9, 115.1 d (J 21),
−113.6,
−116.9
1575
CH2cyclopent), 4.31 c (2H, CH2), 6.99–7.02 m (2H, 116.7 d (J 23), 126.1 d (J 9), 131.1 d (J 2),
Harom), 7.10–7.14 m (2H, Harom), 7.18–7.20 m (2H, 131.4 d (J 8), 132.8 d (J 2), 161.5 d
Harom), 7.28–7.31 m (2H, Harom), 11.95 br.s (1H, NH)
(J 248), 161.8 d (J 244), 181.2, 197.2,
199.9
1670, 1620, 2.48–2.51 m (2H, CH2cyclopent), 2.71–2.73 m (2H, 24.3, 33.6, 45.5, 47.3, 110.6, 110.3, 115.1
−113.5,
−117.2
1580
CH2cyclopent), 4.25 s (2H, CH2), 4.50 d (2H, CH2, J 6.2), d (J 21), 116.2 d (J 22), 129.1 d (J 8),
6.95–6.99 m (2H, Harom), 7.04–7.07 m (2H, Harom), 131.2 d (J 2), 131.4 d (J 8), 161.7 d
7.21–7.26 m (4H, Harom), 10.58 br.s (1H, NH)
(J 244), 162.6 d (J 248), 182.2, 196.7,
199.9
1670, 1620, 2.50–2.52 m (2H, CH2cyclopent), 2.76–2.78 m (2H, 25.4, 33.8, 45.6, 111.3, 113.7 d (J 19),
−116.8,
−133.6,
−137.8
1575
CH2cyclopent), 4.30 c (2H, CH2), 6.95−7.01 m (3H, 115.2 d (J 22), 118.4 d (J 18), 120.4 d.d
Harom), 7.06–7.10 m (1H, Harom), 7.20−7.29 m (3H, (J 5, 4), 130.9 d (J 2), 131.4 d (J 8),
Harom), 12.02 br.s (1H, NH)
133.2 d.d (J 7, 3), 149.3 d.d (J 251, 12),
150.4 d.d (J 252, 14), 161.8 d (J 245),
180.7, 197.5, 199.7
1675, 1620, 2.50–2.52 m (2H, CH2cyclopent), 2.71–2.74 m (2H, 24.3, 33.6, 45.5, 47.5, 110.6, 115.1 d −63.0 (CF3),
Vm
1580
CH2cyclopent), 4.26 s (2H, CH2), 4.60 d (2H, CH2, J 6.3), (J 21), 123.7 d (J 273), 124.1 q (J 3),
6.96–7.00 m (2H, Harom), 7.23–7.26 m (2H, Harom), 125.4 q (J 3), 129.9, 130.5, 131.3 d (J 2),
7.45–7.46 m (1H, Harom), 7.50–7.53 m (2H, Harom), 131.4 d (J 8), 131.7 d (J 33), 136.6, 161.8
−117.1
7.60–7.62 m (1H, Harom), 10.58 br.s (1H, NH)
d (J 244), 182.4, 196.9, 199.5
NMR spectra of enamine derivatives IIIa–IIIp, the
signal of N–H group (strongly bound to the cycle
carbonyl via the hydrogen bond) was observed as
broadened singlet at δ 12.20–13.63 ppm. The signal of
carbon adjacent to nitrogen was found at δ 166.3–
175.4 ppm in 13С NMR spectra of exocyclic enamino-
diketones IIIa–IIIp. IR spectra of the endocyclic
enaminodiketones Va–Vm contained three charac-
teristic absorption bands as well, at 1565–1585, 1605–
1620, and 1670–1685 cm–1, assigned to the double
bond and to conjugated carbonyl bonds of the side
nitrogen was observed at δ 177.7–183.3 ppm, that is, it
was shifted downfield as compared with spectra of the
isomeric exocyclic products IIIa–IIIp.
EXPERIMENTAL
19
1Н, F, and 13С NMR spectra were registered with
the AVANCE 500 (Bruker–Biospin) spectrometer at
500.13 (1H), 470.59 (19F), and 125.77 (13C) MHz using
the 5 mm probe (QNP) with Z-gradient. The spectra
were recorded at 293 K in CDCl3. TMS was used as
the internal reference (1Н and 13С NMR), α,α,α-
trifluorotoluene with δF −63 ppm was used as the
external reference (19F NMR). IR spectra were
recorded using the Bomem Michelson 100 instrument
(KBr pellets in the case of solid products and thin film
in the case of oily products). Melting points were
determined with the Boetius instrument. Elemental
analysis was performed with the Eurovector EA3000
CHNS-O analyzer. The reaction course and the
1
groups and of the cycle, respectively. In H NMR
spectra of enaminodiketones Va–Vm, the signal of
N–H proton bound to the exocyclic carbonyl via the
intramolecular bond was observed as broadened singlet
at δ 10.58–12.41 ppm, that is, it was shifted upfield as
compared with the spectra of the isomeric products
IIIa–IIIp. In the 13С NMR spectra of the endocyclic
products Va–Vm, the signal of carbon adjacent to
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

470
KHLEBNIKOVA et al.
products purity were monitored by TLC (Silufol UV-
254 plates, ethyl acetate – hexane). Column chromato-
graphy was performed on silica gel (70−230 mesh)
NMR spectrum, δ, ppm: 2.45–2.47 m (2H, CH2,cyclopent),
2.74–2.77 m (2H, CH2,cyclopent), 3.82 s (2H, CH2), 6.24
s (1H, Hvinyl), 7.04–7.08 m (2H, Harom), 7.26–7.29 m
(2H, Harom). 13С NMR spectrum, δC, ppm: 28.7, 33.3,
40.6, 115.8 d (J 22 Hz), 116.7, 127.8, 131.0 d (J 8 Hz),
162.4 d (J 247 Hz), 167, 179.7, 206.9. 19F NMR
spectrum, δF: −114.7 ppm.
1
eluting with ethyl acetate – hexane mixture. IR, Н
NMR, 13С NMR, and 19F NMR spectral data of
compounds IIIa–IIIp and Va–Vm are collected in the
table.
2-Acylcyclopentane-1,3-diones (IIa–IIh). A mix-
ture of 4 mmol (0.4 g, 0.55 mL) of triethylamine and
0.2 mL of acetone cyanohydrin was added to the
solution of 2 mmol of enol acylates Ia–Ih in 8 mL of
anhydrous acetonitrile. The reaction mixture was
stirred for 16 h at room temperature, treated with
30 mL of 3% HCl, and extracted with chloroform (3 ×
10 mL); the organic part was washed with water (2 ×
10 mL) and dried over MgSO4. After removal of the
solvent under a reduced pressure compounds IIa–IIh
were obtained in 61–89% yield.
3-Acyloxy-2-cyclopenten-1-ones (Ia–Ig) were pre-
pared following the procedure in [20]. 3-Acetoxy-2-
cyclopenten-1-one (Ia) [20], 3-propyonyloxy-2-
cyclopenten-1-one
(Ib)
[13],
3-cyclopropane-
carbonyloxy-2-cyclopenten-1-one (Ic) [23], and 3-ben-
zoyloxy-2-cyclopenten-1-one (Ie) [13] were identical
to the reference samples.
3-(Furane-2-carbonyloxy)-2-cyclopenten-1-one (Id).
Yield 63%, colorless crystalline solid, mp 108–110°С.
1
IR spectrum, ν, cm−1: 1770, 1710, 1685, 1600. Н
NMR spectrum, δ, ppm: 2.51–2.53 m (2H, CH2,cyclopent),
2.89–2.91 m (2H, CH2,cyclopent), 6.37 s (1H, Hvinyl), 6.63
d.d (1H, Hfuran, J 1.7, 3.5 Hz), 7.41 d (1H, Hfuran, J
3.4 Hz), 6.73 d (1H, Hfuran, J 0.8 Hz). 13С NMR
spectrum, δC, ppm: 28.8, 33.4, 112.6, 116.7, 121.2,
142.6, 148.4, 153.7, 179.3, 206.5.
2-Acetylcyclopentane-1,3-dione (IIa). Yield 72%,
colorless crystalline solid, mp 72–75°С. The spectral
features coincided with the literature data [24].
2-Propyonylcyclopentane-1,3-dione (IIb). Yield
61%, colorless crystalline solid, mp 75–77°С. The
spectral features coincided with the literature data
[13].
3-(2-Fluorobenzoyloxy)-2-cyclopenten-1-one (If).
Yield 72%, colorless crystalline solid, mp 112–114°С.
1
IR spectrum, ν, cm−1: 1765, 1710, 1680, 1600. Н
2-(Cyclopropanecarbonyl)cyclopentane-1,3-dione
NMR spectrum, δ, ppm: 2.52–2.54 m (2H, CH2,cyclopent),
2.90–2.92 m (2H, CH2,cyclopent), 6.40 s (1H, Hvinyl),
7.21–7.25 m (1H, Harom), 7.27–7.32 m (1H, Harom),
7.63–7.68 m (1H, Harom), 8.02–8.05 m (1H, Harom). 13С
NMR spectrum, δC, ppm: 28.9, 33.6, 116.8 d (J 9 Hz),
117.2, 117.6 d (J 22 Hz), 124.5 d (J 3 Hz), 132.7,
136.4 d (J 9 Hz), 159.7 d (J 4 Hz), 162.6 d (J 263 Hz),
179.6, 206.7. 19F NMR spectrum, δF: −107.5 ppm.
(IIc). Yield 76%, colorless crystalline solid, mp 46–
1
49°С. IR spectrum, ν, cm−1: 1705, 1620, 1585. Н
NMR spectrum, δ, ppm: 1.17–1.20 m (2H, CH2,cycloprop),
1.31–1.34 m (2H, CH2,cycloprop), 2.54–2.57 m (2H,
CH2,cyclopent), 2.73–2.75 m (2H, CH2,cyclopent), 3.15–3.20
m (1H, CHcycloprop). 13С NMR spectrum, δC, ppm: 13.7,
16.5, 28.5, 33.9, 114.1, 200.6, 201.3, 204.3. Found, %:
C 65.01; H 6.10. C9H10O3. Calculated, %: C 65.05; H
6.07.
3-(3-Fluorobenzoyloxy)-2-cyclopenten-1-one (Ig).
Yield 70%, colorless crystalline solid, mp 98–101°С.
2-(Furan-2-carbonyl)cyclopentane-1,3-dione (IId).
1
IR spectrum, ν, cm−1: 1750, 1705, 1680, 1600. Н
Yield 81%, colorless crystalline solid, mp 115–118°С.
1
IR spectrum, ν, cm−1: 1690, 1620, 1580. Н NMR
NMR spectrum, δ, ppm: 2.53–2.56 m (2H, CH2,cyclopent),
2.91–2.94 m (2H, CH2,cyclopent), 6.40 s (1H, Hvinyl),
7.36–7.40 m (1H, Harom), 7.50–7.54 m (1H, Harom),
spectrum, δ, ppm: 2.60–2.62 m (2H, CH2,cyclopent),
2.83–2.85 m (2H, CH2,cyclopent), 6.66 d.d (1H, Hfuran, J
1.6, 3.8 Hz), 6.78 d (1H, Hfuran, J 0.8 Hz), 8.82 d (1H,
13
7.80–7.82 m (1H, Harom), 7.93–7.95 m (1H, Harom). С
NMR spectrum, δC, ppm: 28.8, 33.5, 117.1, 117.3,
121.7 d (J 21 Hz), 126.2 d (J 2 Hz), 130.2 d (J 7 Hz),
130.6 d (J 8 Hz), 161.1 d (J 2 Hz), 162.6 d (J 248 Hz),
179.4, 206.5. 19F NMR spectrum, δF: −111.4 ppm.
H
furan, J 3.8 Hz), 16.71 br.s (1H, OH). 13С NMR
spectrum, δC, ppm: 29.3, 33.5, 111.8, 113.4, 126.0,
148.9, 149.2, 176.6, 198.1, 207.9. Found, %: C 62.47;
H 4.24. C10H8O4. Calculated, %: C 62.50; H 4.20.
2-Benzoylcyclopentane-1,3-dione (IIe). Yield 82%,
colorless crystalline solid, mp 45–47°С. The spectral
features coincided with the literature data [13].
3-(4-Fluorophenylacetoxy)-2-cyclopenten-1-one
(Ih). Yield 80%, colorless crystalline solid, mp 58–62°С.
1
IR spectrum, ν, cm−1: 1790, 1715, 1680, 1600. Н
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

PREPARATION OF FLUORINE-CONTAINING EXO- AND ENDOCYCLIC ENAMINE
471
2-(2-Fluorobenzoyl)cyclopentane-1,3-dione (IIf).
%: C 66.98; H 5.15; N 6.04. C13H12FNO2. Calculated,
%: C 66.94; H 5.19; N 6.01.
Yield 85%, yellow oily substance. IR spectrum, ν,
1
cm−1: 1700, 1630, 1580. Н NMR spectrum, δ, ppm:
2-[1-(4-Fluorobenzylamino)ethylidene]cyclopentane-
1,3-dione (IIIb). Yield 78%, mp 94–96°С. Found, %:
C 68.03; H 5.70; N 5.70. C14H14FNO2. Calculated, %:
C 68.00; H 5.71; N 5.66.
2.55–2.58 m (2H, CH2,cyclopent), 2.82–2.85 m (2H,
CH2,cyclopent), 7.12–7.15 m (1H, Harom), 7.22–7.27 m
(1H, Harom), 7.51–7.54 m (2H, Harom). 13С NMR spec-
trum, δC, ppm: 28.3 br.s, 33.4 br.s, 115.1, 116.1 d (J
22 Hz), 117.2 d (J 22 Hz), 124.1 d (J 2 Hz), 130.0,
134.2 d (J 9 Hz), 160.6 d (J 254 Hz), 190.4, 197.7
br.s, 204.4 br.s. 19F NMR spectrum, δF −111.8 ppm.
Found, %: C 65.43; H 4.10. C12H9FO3. Calculated, %:
C 65.45; H 4.12.
2-[1-(4-Fluorophenylamino)propylidene]cyclo-
pentane-1,3-dione (IIIc). Yield 83%, mp 135–137°С.
Found, %: C 67.98; H 5.71; N 5.65. C14H14FNO2.
Calculated, %: C 68.00; H 5.71; N 5.66.
2-[1-(4-Fluorobenzylamino)propylidene]cyclo-
pentane-1,3-dione (IIId). Yield 69%, mp 94–96°С.
Found, %: C 68.93; H 6.20; N 5.40. C15H16FNO2.
Calculated, %: C 68.95; H 6.17; N 5.36.
2-(3-Fluorobenzoyl)cyclopentane-1,3-dione (IIg).
Yield 89%, yellow oily substance. IR spectrum, ν,
1
cm−1: 1700, 1630, 1580. Н NMR spectrum, δ, ppm:
2.63–2.85 m (4H, CH2,cyclopent), 7.27–7.34 m (1H,
2-[Cyclopropyl-(4-fluorophenylamino)methylene]-
cyclopentane-1,3-dione (IIIe). Yield 55%, mp 79–82°С.
Found, %: C 69.45; H 5.42; N 5.37. C15H14FNO2.
Calculated, %: C 69.49; H 5.44; N 5.40.
H
H
arom), 7.44–7.48 m (1H, Harom), 7.76–7.79 m (1H,
arom), 7.87–7.91 m (1H, Harom). 13С NMR spectrum,
δC, ppm: 28.9 br.s, 33.5 br.s, 113.5, 116.8 d (J 24 Hz),
120.9 d (J 21 Hz), 125.9 d (J 2 Hz), 129.8 d (J 8 Hz),
136.8 d (J 4 Hz), 162.4 d (J 247 Hz), 191.7, 198.2 br.s,
207.1 br.s. 19F NMR spectrum, δF: −112.6 ppm. Found,
%: C 65.42; H 4.15. C12H9FO3. Calculated, %: C
65.45; H 4.12.
2-[Cyclopropyl-(4-fluorobenzylamino)methyl-
ene]cyclopentane-1,3-dione (IIIf). Yield 79%, mp
82–83°С. Found, %: C 70.34; H 5.94; N 5.16.
C16H16FNO2. Calculated, %: C 70.31; H 5.90; N 5.12.
2-[(4-Fluorophenylamino)(furan-2-yl)methylene]-
cyclopentane-1,3-dione (IIIg). Yield 54%, mp 128–
130°С. Found, %: C 67.36; H 4.25; N 4.88. C16H12FNO3.
Calculated, %: C 67.36; H 4.24; N 4.91.
2-(4-Fluorophenylacetyl)cyclopentane-1,3-dione
(IIh). Yield 86%, yellow oily substance. IR spectrum,
ν, cm−1: 1705, 1635, 1590. 1Н NMR spectrum, δ, ppm:
2.53–2.55 m (2H, CH2,cyclopent), 2.73–2.76 m (2H,
CH2,cyclopent), 4.20 s (2H, CH2), 6.99–7.05 m (2H,
2-[(4-Fluorobenzylamino)(furan-2-yl)methylene]-
cyclopentane-1,3-dione (IIIh). Yield ход 51%, mp
123–126°С. Found, %: C 68.19; H 4.74; N 4.62.
C17H14FNO3. Calculated, %: C 68.22; H 4.71; N 4.68.
H
arom), 7.23–7.30 m (2H, Harom). 13С NMR spectrum,
δC, ppm: 28.1, 33.6, 43.8, 114.0, 115.4 d (J 21 Hz),
129.2 d (J 2 Hz), 131.4 d (J 8 Hz), 162.1 d (J 246 Hz),
198.8, 199.8, 204.2. 19F NMR spectrum, δF: −115.8 ppm.
Found, %: C 66.63; H 4.77. C13H11FO3. Calculated, %:
C 66.66; H 4.73.
2-[Phenyl-(4-fluorophenylamino)methylene]cyclo-
pentane-1,3-dione (IIIi). Yield 57%, mp 162–164°С.
Found, %: C 73.24; H 4.74; N 4.70. C18H14FNO2.
Calculated, %: C 73.21; H 4.78; N 4.74.
Exocyclic enaminodiketones (IIIa–IIIp). 1 mmol
of the amine (4-fluoroaniline, 3,4-difluoroaniline, 4-
fluorobenzylamine, or 3-trifluoromethylbenzylamine)
was added to the solution of 1 mmol of the triketone
(IIa–IIh) in benzene. The reaction mixture was
refluxed with the Dean-Stark trap (4 h in the cases of
4-fluorobenzylamine and 3-trifluoromethylbenzyl-
amine, 30 h in the cases of 4-fluoroaniline and 3,4-
difluoroaniline). After removal of the solvent under a
reduced pressure compounds IIIa–IIIp were isolated
as colorless crystalline solids (yield of 50–83%) by
column chromatography.
2-[Phenyl-(4-fluorobenzylamino)methylene]cyclo-
pentane-1,3-dione (IIIj). Yield 52%, mp 155–156°С.
Found, %: C 73.81; H 5.24; N 4.51. C19H16FNO2.
Calculated, %: C 73.77; H 5.21; N 4.53.
2-[(4-Fluorobenzylamino)(2-fluorophenyl)methyl-
ene]cyclopentane-1,3-dione (IIIk). Yield 58%, mp
145–148°С. Found, %: C 69.76; H 4.64; N 4.30.
C19H15F2NO2. Calculated, %: C 69.72; H 4.62; N 4.28.
2-[(3-Fluorophenyl)(4-fluorophenylamino)methyl-
ene]cyclopentane-1,3-dione (IIIl). Yield 50%, mp
151–154°С. Found, %: C 68.96; H 4.16; N 4.45.
C18H13F2NO2. Calculated, %: C 69.01; H 4.18; N 4.47.
2-[1-(4-Fluorophenylamino)ethylidene]cyclopentane-
1,3-dione (IIIa). Yield 75%, mp 122–124°С. Found,
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KHLEBNIKOVA et al.
2-[(4-Fluorobenzylamino)-(3-fluorophenyl)methyl-
3-(4-Fluorobenzylamino)-2-(cyclopropanecar-
bonyl)-2-cyclopenten-1-one (Vd). Yield 78%, mp
129–132°C. Found, %: C 70.28; H 5.87; N 5.13.
C15H14FNO2. Calculated, %: C 70.31; H 5.90; N 5.12.
ene]cyclopentane-1,3-dione (IIIm). Yield 54%, mp
136–139°С. Found, %: C 69.69; H 4.66; N 4.25.
C19H15F2NO2. Calculated, %: C 69.72; H 4.62; N 4.28.
2-[2-(4-Fluorophenyl)-1-(4-fluorophenylamino)-
ethylidene]cyclopentane-1,3-dione (IIIn). Yield
55%, mp 144–147°C. Found, %: C 69.68; H 4.60; N
4.31. C19H15F2NO2. Calculated, %: C 69.72; H 4.62; N
4.28.
3-(4-Fluorophenylamino)-2-(furan-2-carbonyl)-
2-cyclopenten-1-one (Ve). Yield 67%, mp 167–168°C.
Found, %: C 67.31; H 4.27; N 4.93. C16H12FNO3.
Calculated, %: C 67.36; H 4.24; N 4.91.
3-(4-Fluorobenzylamino)-2-(furan-2-carbonyl)-
2-cyclopenten-1-one (Vf). Yield 58%, mp 119−121°C.
Found, %: C 68.18; H 4.71; N 4.68. C17H14FNO3.
Calculated, %: C 68.22; H 4.71; N 4.68.
2-[1-(4-Fluorobenzylamino)-2-(4-fluorophenyl)-
ethylidene]cyclopentane-1,3-dione (IIIo). Yield
53%, mp 114–117°C. Found, %: C 70.30; H 5.00; N
4.11. C20H17F2NO2. Calculated, %: C 70.37; H 5.02; N
4.10.
2-Benzoyl-3-(4-fluorophenylamino)-2-cyclo-
penten-1-one (Vg). Yield 61%, mp 140–143°C.
Found, %: C 73.16; H 4.75; N 4.70. C18H14FNO2.
Calculated, %: C 73.21; H 4.78; N 4.74.
2-[2-(4-Fluorophenyl)-1-(3-trifluoromethylbenzyl-
amino)ethylidene]cyclopentane-1,3-dione (IIIp).
Yield 50%, mp 57–60°C. Found, %: C 64.41; H 3.50;
N 3.55. C21H17F4NO2. Calculated, %: C 64.45; H 3.48;
N 3.58.
2-Benzoyl-3-(4-fluorobenzylamino)-2-cyclo-
penten-1-one (Vh). Yield 54%, mp 129–131°C.
Found, %: C 73.81; H 5.24; N 4.51. C19H16FNO2.
Calculated, %: C 73.77; H 5.21; N 4.53.
Endocyclic enaminodiketones (Va–Vm). Oxalyl
chloride (10 mmol) was added to 1 mmol of triketone
IIb–IIh, and the reaction mixture was stirred for 10–
30 min at room temperature. (In the case of
IIa: 1 mmol of IIa was dissolved in 30 mL of
anhydrous chloroform, then 5 mmol of oxalyl chloride
was added, and the reaction mixture was refluxed for
2.5 h). The excess of oxalyl chloride and the solvent
were removed under a reduced pressure. The residue
was dissolved in 20 mL of chloroform; 2 mmol of the
amine (4-fluoroaniline, 3,4-difluoroaniline, 4-fluoro-
benzylamine, or 3-trifluoromethylbenzylamine) was
added, and the mixture was stirred for 2 h at room
temperature. After removal of the solvent under a
reduced pressure compounds Va–Vm were isolated as
colorless crystalline solids (yield of 54–78%) by
column chromatography.
3-(4-Fluorobenzylamino)-2-(3-fluorobenzoyl)-2-
cyclopenten-1-one (Vi). Yield 67%, mp 97–100°C.
Found, %: C 69.77; H 4.64; N 4.30. C19H15F2NO2.
Calculated, %: C 69.72; H 4.62; N 4.28.
3-(4-Fluorophenylamino)-2-(4-fluorophenyl-
acetyl)-2-cyclopenten-1-one (Vj). Yield 55%, mp
106–109°C. Found, %: C 69.65; H 4.60; N 4.30.
C19H15F2NO2. Calculated, %: C 69.72; H 4.62; N 4.28.
3-(4-Fluorobenzylamino)-2-(4-fluorophenyl-
acetyl)-2-cyclopenten-1-one (Vk). Yield 63%, mp
87–89°C. Found, %: C 70.31; H 5.04; N 4.14.
C20H17F2NO2. Calculated, %: C 70.37; H 5.02; N 4.10.
3-(3,4-Difluorophenylamino)-2-(4-fluorophenyl-
acetyl)-2-cyclopenten-1-one (Vl). Yield 64%, mp
109−111°C. Found, %: C 66.04; H 4.13; N 4.10.
C19H14F3NO2. Calculated, %: C 66.09; H 4.09; N 4.06.
2-Acetyl-3-(4-fluorophenylamino)-2-cyclopenten-
1-one (Va). Yield 64%, mp 136–139°C. Found, %: C
66.98; H 5.22; N 6.05. C13H12FNO2. Calculated, %: C
66.94; H 5.19; N 6.01.
3-(3-Trifluoromethylbenzylamino)-2-(4-fluoro-
phenylacetyl)-2-cyclopenten-1-one (Vm). Yield 55%,
mp 81–83°C. Found, %: C 64.49; H 4.38; N 3.56.
C21H17F4NO2. Calculated, %: C 64.45; H 4.38; N 3.58.
2-Propionyl-3-(4-fluorophenylamino)-2-cyclo-
penten-1-one (Vb). Yield 71%, mp 145–147°C. Found,
%: C 67.96; H 5.73; N 5.63. C14H14FNO2. Calculated,
%: C 68.00; H 5.71; N 5.66.
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C15H14FNO2. Calculated, %: C 69.49; H 5.44; N 5.40.
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