Condensation of 2-polyfluoroacycloalkanones with aldehydes and dimethylformamide-dimethylacetal

Article abstract of DOI:10.1071/CH01027

Polyfluorinated 1,3-diketones containing carbocycles react with aldehydes under Lewis-acid catalysis and also with dimethylformamide-dimetylacetal without catalysis, yielding exclusively (E)-configured condensation products involving the methylene group of the carbocycle. Novel trifluoromethylated chromenes are prepared from 2-trifluoroacetylcycloalkanones and salicylaldehyde. The structures of two new compounds, 2-(E)-benzylidene-6-trifluoroacetylcyclohexanone and 4-trifluoroacetyl-2,3-dihydro-1H-xantene, are confirmed by X-ray structure analysis.

Full text of DOI:10.1071/CH01027

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Full Papers
Aust. J. Chem. 2001, 54, 157–163
Condensation of 2-Polyfluoroacylcycloalkanones with Aldehydes
and Dimethylformamide–Dimethylacetal
D. V. Sevenard,A O. G. Khomutov,B M. I. Kodess,B K. I. Pashkevich,B I. Loop,A
E. LorkA and G.-V. RöschenthalerA,C
A Institute of Inorganic & Physical Chemistry, University of Bremen, Leobener Strasse, 28334 Bremen, Germany.
B Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, 20 ul. S. Kovalevskoy,
620219 Ekaterinburg, Russia.
C Author to whom correspondence should be adressed (e-mail: gvr@chemie.uni-bremen.de).
Polyfluorinated 1,3-diketones containing carbocycles react with aldehydes under Lewis-acid catalysis and also with
dimethylformamide–dimetylacetal without catalysis, yielding exclusively (E)-configured condensation products
involving the methylene group of the carbocycle. Novel trifluoromethylated chromenes are prepared from
2-trifluoroacetylcycloalkanones and salicylaldehyde. The structures of two new compounds, 2-(E)-benzylidene-6-
trifluoroacetylcyclohexanone and 4-trifluoroacetyl-2,3-dihydro-1H-xantene, are confirmed by X-ray structure
analysis.
Manuscript received: 28 March 2001.
Final version: 22 May 2001.
CH01027
C
a
A
M
A
Recently, we showed[10] that 2-trifluoroacetylcyclohex-
Introduction
anone and methyl trifluoroacetate give the Claisen-conden-
sation product (at the 6-position of cyclohexanone) under
base catalysis. In continuation of a systematic investigation
of the chemical properties[11] of 2-polyfluoroacylcycloal-
kanones, we have studied their behavior in reactions with se-
lected C-electrophiles.
The Knoevenagel condensation of linear 1,3-dicarbonyls
with electrophiles like aromatic aldehydes, in the presence of
bases, straightforwardly yields addition products involving
the active methylene group of the nucleophile.[1] This
reaction is considered an important method for the synthesis
of highly reactive 2-aryliden-1,3-dicarbonyls.[2]
Results and Discussion
Using an unsymmetrical 1,3-diketone, e.g. 1,1,1-
trifluoropentane-2,4-dione, as the nucleophile resulted in,
along with the expected compound, products of condensation
at the methyl group, and moreover, trifluoromethylstyryl
ketones. The products’ ratio depends on the reaction
conditions and on the substituent properties in the aromatic
aldehyde ring.[3] Only in the case of 4,4,4-trifluoro-1-
phenylbutane-1,3-dione and 2,4,6-trimethylbenzaldehyde
was the ‘normal’ Knoevenagel reaction observed to afford a
trifluoromethylated 2-arylidene-1,3-diketone.[3]
2-Polyfluoroacylcycloalkanones (1–6) and the aromatic
aldehydes (7–11,13) (in boiling propan-2-ol, BF3·OEt2
catalysis) gave enediones (14–16,18–21,23–31) in good to
excellentyields. Onlythereactionwitho-chlorobenzaldehyde
(12) resulted in the formation of compounds (17) and (22) in
15 and 18% yields, respectively (Scheme 1, Table 1).
Non-fluorinated 2-acetylcycloalkanones, considered 1,3-
diketones with an alkyl substituent in the 2-position at which
condensation is not possible, react easily with aromatic
aldehydes to give products of a twofold condensation at the
activated methyl and methylene moiety.[4] Similar
condensation products involving the methylene group in the
γ-position of the β-dicarbonyl system have been obtained by
treating 2-carbalkoxycyclopentanones with aromatic
aldehydes and cinnamaldehyde.[5]
The reaction pathway in the case of dimethylformamide–
dimethylacetal (DMF–DMA) depends mainly on the
properties of the nucleophile; for non-fluorinated linear 1,3-
diketones the condensation proceeds at the activated
methylene fragment,[6,7] for non-fluorinated 2-acetylcyclo-
alkane-1,3-diones[8] and for trifluoromethylated β-amino-
enones[9] condensation at the methyl group was reported.
Scheme 1. Reaction of 2-polyfluoroacylcycloalkanones with
aromatic aldehydes.
© CSIRO 2001
10.1071/CH01027
0004-9425/01/030157

158
D. V. Sevenard et al.
Table 1. Preparation and properties of compounds (14–38,40)
Compound
Starting
Materials
M.p. (°C)
(solvent)
Formula
Found/Calc. Anal. (%)
Yield
(%)
Reaction
time (h)
or HRMS (m/z)
C
H
F
N
(14)
5-Trifluoroacetyl-2-(E)-
(p-dimethylaminobenzylidene)-
cyclopentanone
(1) and (7)
182–183
C16H16F3NO2
61.9
61.7
5.3
5.2
17.8
18.3
4.7
4.5
92
5
(toluene)
(15)
(16)
(17)
5-Trifluoroacetyl-2-(E)-
(1) and (10)
(1) and (11)
(1) and (12)
94–95
(hexane)
102–103
C15H13F3O3
C14H11F3O2
60.5
60.4
62.7
62.7
4.4
4.4
4.1
4.1
18.9
19.1
21.5
21.3
–
–
68
67
15
5
(p-methoxybenzylidene)cyclopentanone
2-(E)-Benzylidene-5-
10
10
trifluoroacetylcyclopentanone
2-(E)-(o-Chlorobenzylidene)-5-
trifluoroacetylcyclopentanone
(petroleum ether/toluene, 4:1)
115–117
(perfluoro-1,1-
dimethylcyclohexane)
161–163
C14H10ClF3O2,
302.0318. 302.0321.
1.1 ppm (10.0), 0.3 mmu (30.0)
(18)
(19)
(20)
(21)
(22)
6-Trifluoroacetyl-2-(E)-
(p-dimethylaminobenzylidene)-cyclohexanone
2-(E)-(p-Diethylaminobenzylidene)-6-
trifluoroacetylcyclohexanone
6-Trifluoroacetyl-2-(E)-
(p-methoxybenzylidene)cyclohexanone
2-(E)-Benzylidene-6-
(2) and (7)
(2) and (8)
(2) and (10)
(2) and (11)
(2) and (12)
C17H18F3NO2
62.6
62.8
64.5
64.6
61.4
61.5
63.9
63.8
5.6
5.6
6.2
6.3
4.9
4.8
4.7
4.6
17.6
17.5
16.5
16.1
18.5
18.3
20.2
20.2
4.3
4.3
4
71
76
61
95
18
5
(petroleum ether/toluene, 4:1)
96–97
C19H22F3NO2
11
16
16
20
(petroleum ether)
112–113
4
–
–
C16H15F3O3
C15H13F3O2
(toluene)
110–111
(petroleum ether)
57
–
–
trifluoroacetylcyclohexanone
2-(E)-(o-Chlorobenzylidene)-6-
trifluoroacetylcyclohexanone
C
15H12ClF3O2,
316.0484. 316.0478.
–2.1 ppm (10.0), –0.6 mmu (10.0)
(perfluoro-1,1-
dimethylcyclohexane)
92–93
(23)
(24)
(25)
(26)
(27)
(28)
2-(E)-(p-Diethylaminobenzylidene)-6-
(2,2,3,3-tetrafluoropropanoyl)cyclohexanone
2-(E)-(p-Methoxybenzylidene)-6-(2,2,3,3-
tetrafluoropropanoyl)cyclohexanone
2-(E)-Benzylidene-6-(2,2,3,3-
(3) and (8)
(3) and (10)
(3) and (11)
(4) and (9)
(4) and (13)
(5) and (7)
C20H23F4NO2
62.3
62.3
59.3
59.3
61.8
61.2
55
6.2
6
19.7
19.7
22.3
22.1
–
3.4
3.6
–
71
66
72
78
70
97
11
16
16
10
10
5
(petroleum ether)
76–78
(petroleum ether)
64–65
(petroleum ether)
90.0–90.5
C
17H16F4O3
16H14F4O2
4.6
4.7
5.1
4.5
3.6
3.8
3.4
3.4
4.2
–
C
–
–
–
tetrafluoropropanoyl)cyclohexanone
6-Perfluoropropanoyl-2-(E)-
–
C16H13F5O3
14H11F5O3
19H18F7NO2
27.4
27.3
29.3
29.5
31.2
(p-hydroxybenzylidene)cyclohexanone
6-Perfluoropropanoyl-2-(E)-(2-
(hexane)
67
(hexane)
55.2
52.3
52.2
53.8
–
–
–
C
furfurylydene)cyclohexanone
6-Perfluorobutanoyl-2-(E)-
126–127
C
3.4
(petroleum ether)
(p-dimethylaminobenzylidene)cyclohexanone
6-Perfluorobutanoyl-2-(E)-
(p-methoxybenzylidene)cyclohexanone
2-(E)-Benzylidene-6-
53.6
52.6
52.4
53.6
53.4
4.3
3.9
3.7
3.3
3.4
31.3
32.5
32.3
34.6
34.8
3.3
–
–
(29)
(30)
(31)
(32)
(33)
(34)
(35)
(36)
(37)
(38)
(40)
(5) and (10)
(5) and (11)
(6) and (7)
77–78
(hexane)
Oil
C18H15F7O3
C17H13F7O2
73
56
64
30
21
21
13
19
51
74
52
5
5
–
perfluorobutanoylcyclohexanone
2-(E)-(p-Dimethylaminobenzylidene)-6-
perfluoropentanoylcyclohexanone
4-Trifluoroacetyl-2,3-dihydro-
1H-xanthene
–
127–128
(hexane)
C20H18F9NO2,
475.1174. 475.1194.
4.1 ppm (10.0), 2.0 mmu (30.0)
5
(2) and
salicylaldehyde
(1) and
118–119
(petroleum ether)
>180A
C15H11F3O2
64.3
64.3
60
4
4
3.9
3.9
20.4
20.3
–
–
–
–
10
3
5-Trifluoroacetyl-2-(E)-(o-
C14H11F3O3
hydroxybenzylidene)cyclopentanone
3-Trifluoroacetyl-2,3-dihydro-
1H-cyclopenta-[b]-chromene
2-(E)-Cinnamylidene-5-
trifluoroacetylcyclopentanone
2-(E)-Cinnamylidene-6-
salicylaldehyde
(33)
(toluene)
59.2
–
119.5–120.0
(petroleum ether)
152–154
C14H9F3O2,
C16H13F3O2,
C17H15F3O2,
C10H12F3NO2
C11H14F3NO2
C18H19F4NO2
266.0536. 266.0555.
1
7.2 ppm (20.0), 1.9 mmu (4.0)
294.0861. 294.0868.
2.2 ppm (10.0), 0.6 mmu (5.0)
308.1012. 308.1024.
(1) and
cinnamaldehyde
(2) and
4
(hexane)
124–126
3
trifluoroacetylcyclohexanone
2-(E)-Dimethylaminomethylene-5-
trifluoroacetylcyclopentanone
2-(E)-Dimethylaminomethylene-6-
trifluoroacetylcyclohexanone
2-(E)-(p-Dimethylaminobenzylidene)-6-
(2,2,3,3-tetrafluoropropanoyl)cyclohexanone
cinnamaldehyde
(1) and
DMF–DMA
(2) and
DMF–DMA
(39) and (7)
(petroleum ether)
115–118
(hexane/ethanol, 10:1)
101–103
(hexane/ethanol, 10:1)
124–125
3.9 ppm (10.0), 1.2 mmu (5.0)
51.2
51.1
53.2
53.0
60.7
5.2
5.1
5.6
5.7
5.2
24.6
24.2
22.9
22.9
20.9
5.8
6.0
5.6
5.6
3.9
2
2
6
(petroleum ether)
60.5
5.4
21.3
3.9
A Sublimation point.
In the X-ray structure analysis (Table 2,3) of (21) two
independent molecules, (A) and (B), were found. The
existence of the endo-enol form (Fig. 1) was shown. The enol
proton was found at O(2) [O(2A)], the C(2)–O(1) [C(2A)–
O(1A)] distance is shorter than the C(8)–O(2) [C(8A)–
O(2A)] distance, 125.8(3) [125.4(3)] pm and 133.8(3)
[133.1(3)] pm, respectively. The phenyl ring is twisted with
respect to the rest of the molecule with the torsion angle
C(7)–C(9)–C(10)–C(15) 33.9° for (A) [–151.3° for the
corresponding angle in molecule (B)]. The O(1)–C(2)–C(3)–
C(8)–O(2)–H[O(2)] and O(1A)–C(2A)–C(3A)–C(8A)–
O(2A)–H[O(2A)] systems are planar. The cyclohexane ring
possesses a ‘half-chair’ conformation where C(5) [C(5A)] is
above the ring atoms by 67.2 [65.4] pm. The calculated
torsion angles are 2.6° for O(2)–C(8)–C(3)–C(2), –4.5° for
C(8)–C(3)–C(2)–O(1), 1.4° for O(2A)–C(8A)–C(3A)–
C(2A) and –1.0° for C(8A)–C(3A)–C(2A)–O(1A) (in
contrast, the endo-enol form of 2-trifluoroacetyl-
cyclohexanone (2) exhibits a non-planar chelate ring with the
corresponding MINDO/3 calculated torsion angles[12] of
5.5° and 17.8°). In the O–H–O bridge of (21), [O(2)–O(1)
249.0 pm; O(2A)–O(1A) 247.8 pm], a small deviation from
linearity was observed (O(1)–H(2)–O(2) = 164.2°, O(1A)–
H(2A)–O(2A) = 151.7°), compared with the endo-enol form
of 2-trifluoroacetylcyclohexanone with angle O–H–O =
122.0°.[12]

Condensation of 2-Polyfluoroacylcycloalkanones with Aldehydes and DMF–DMA
159
Table 2. Details of crystal data, measurement of intensities, and data processing of the X-ray diffraction investigation of compounds (21) and (32)
(21)
(32)
(21)
(32)
FW
282.25
280.24
0.9 × 0.7 × 0.5
Monoclinic
P21/c
µ(Mo Kα) (mm–1
2θ range (°)
F(000)
)
0.126
2.59 to 27.50
1168
–13 ≤ h ≤ 1,
–32 ≤ k ≤ 1,
–13 ≤ l ≤ 13
6486
0.129
2.40 to 25.00
576
–8 ≤ h ≤ 8,
–21 ≤ k ≤ 21,
–11 ≤ l ≤ 12
8292
Crystal size (mm) 0.6 × 0.5 × 0.4
Crystal system
Space group
Monoclinic
P21/n
Index range
a (pm)
b (pm)
c (pm)
β (°)
1006.60 (10)
2495.8 (2)
1015.50 (10)
91.460 (10)
2.5504 (4)
8
1011.30 (10)
1775.6 (4)
716.70 (10)
106.710 (10)
1.2326 (3)
4
Reflections collected
Independent reflections
Completeness to θmax
Data/Restraints/Parameter
Goodness-of-fit at F2
5125 [Rint = 0.0246]
87.7%
2176 [Rint = 0.0411]
99.9%
5125/0/372
1.044
R1 = 0.0581,
wR2 = 0.1275
0.273 and –0.301
2176/0/183
1.037
R1 = 0.0424,
wR2 = 0.1090
0.220 and –0.269
V (nm3)
Z
Final R indiced [I > 2σ(I)]
Dc (Mg/m3)
1.470
1.510
Largest diff. peak and hole (e·Å–
)
3
The two 2-trifluoroacetylcycloalkanones (1) and (2) react
with salicylaldehyde differently; in the case of the
cyclohexane derivative (2) the product of condensation and
heterocyclization (32) was isolated (Scheme 2, Table 1).
With the cyclopentane 1,3-diketone (1) the o-hydroxy-
substituted enedione (33) is formed, which is transformed
into the corresponding heterocycle (34) by heating in conc.
H2SO4 (Scheme 2, Table 1).
twisted conformation with C(5) 47.7 pm above and C(7) 25.9
pm under the C(3)–C(4)–C(7)–C(8) plane. The trifluoro-
acetyl group is slightly twisted towards the conjugated C(3)–
C(8)–C(7)–C(15) system with a torsion angle C(1)–C(2)–
C(3)–C(8) of 9.8°.
Reacting 1,3-diketones (1,2) with cinnamaldehyde under
the conditions mentioned above, yellow crystalline
(E)-cinnamylidene derivatives (35) and (36) were formed
(Scheme 3, Table 1) with low yields [13% (35), 19% (36)],
as in the case of the analogous cinnamylidene-2-carbalkoxy
cyclopentanones.[5]
The molecular structure of (32) (Fig. 2, Table 2,3) showed
a planar chromene system. The cyclohexane ring has a
1,1,1,5,5,5-Hexafluoropentane-2,4-dione and DMF, when
heated in acetic anhydride, gave straightforwardly the 3-
dimethylaminomethylene-substituted derivative,[13] whereas
1,3-diketone (2) produced a complex mixture of several
products. When one equivalent of 2-trifluoroacetylcyclo-
alkanone (1) or (2) was reacted with 1.1 equivalents of
DMF–DMA in boiling toluene, compounds (37) and (38)
(51 and 74% yield, respectively) were obtained (Scheme 4,
Table 1).
1,1,1-Trifluoropentane-2,4-dione and benzaldehyde
(heating in propan-2-ol in the presence of BF3·OEt2, or
DMF–DMA, heating in toluene) produce an inseparable
mixture of compounds similar to a previous case.[3]
Apparently, the condensation took place not only at the
activated 1,3-diketone methylene group, but also at the
methyl group, generating (E)- and (Z)-isomers with respect
to the dimethylaminomethylene C–C double bond.
Table 3. The selected bond lengths (pm) and angles (°) of com-
pounds (21) and (32)
(21)
(32)
C(2)–O(1)
C(2)–C(3)
C(3)–C(8)
C(8)–O(2)
125.8(3)
140.8(4)
139.5(3)
133.8(3)
125.4(3)
141.6(4)
138.9(3)
133.1(3)
125.4(2)
117.9(2)
120.6(2)
C(2)–O(1)
C(2)–C(3)
C(3)–C(8)
C(3)–C(4)
C(6)–C(7)
C(7)–C(15)
C(7)–C(8)
C(8)–O(2)
O(1)–C(2)–C(3) 122.36(16)
C(8)–C(3)–C(2) 127.38(15)
C(5)–C(4)–C(3) 113.25(16)
C(4)–C(5)–C(6) 110.79(16)
C(7)–C(6)–C(5) 109.98(15)
O(2)–C(8)–C(3) 118.22(15)
123.1(2)
144.4(3)
136.6(3)
151.9(2)
150.8(2)
134.2(3)
144.8(2)
136.19(19)
C(2A)–O(1A)
C(2A)–C(3A)
C(3A)–C(8A)
C(8A)–O(2A)
O(1)–C(2)–C(3)
C(8)–C(3)–C(2)
O(2)–C(8)–C(3)
O(1A)–C(2A)–C(3A) 125.1(2)
C(8A)–C(3A)–C(2A) 117.7(2)
O(2A)–C(8A)–C(3A) 120.7(2)
β-Aminoenone (39) [amino derivative of 1,3-diketone
(3)] and p-dimethylaminobenzaldehyde (7) (Scheme 5, Table
1), under acid-catalysis, gave enedione (40) in 52% yield,
which was formed by hydrolysis of the enamine function.
The 1H and 19F nuclear magnetic (NMR) spectra (Table 4)
of compounds (37) and (38) in CDCl3 exhibit only one set of
signals. The data confirms the presence of an enol form,
since the formation of an ammonium zwitter-ion[14] could be
ruled out on the basis of the 1H NMR data. There is a broad
signal at δH > 14 corresponding to the enol proton (the signal
of the Me2NH+ group could be observed at ca. δH = 9.5[15]).
The enol tautomer was observed in the 1H NMR spectra for
compounds (14–31,33,35,36,40) in CDCl3 (Table 5, 6) with
Figure 1. Molecular structure of (21) (with two independent
molecules (A) and (B), thermal ellipsoids with 50% probability).

160
D. V. Sevenard et al.
Scheme 3. Reaction of 2-trifluoroacetylcycloalkanones with
cinnamaldehyde.
Scheme 2. Reaction of 2-trifluoroacetylcycloalkanones with
salicylaldehyde.
Scheme 4. Reaction of 2-trifluoroacetylcycloalkanones with DMF–
DMA.
Scheme 5. Reaction of the 1-[N-(p-tolyl)-amino]-2-(2,2,3,3-
tetrafluoropropanoyl)cyclohexene with p-dimethylaminobenzal-
dehyde.
Table 4. 1H and 19F NMR data of compounds (37) and (38)
Comp.
1H NMR d, J (Hz)
CH3 =CH
19F NMR δ
Figure 2. Molecular structure of compound (32) (thermal ellipsoids
with 50% probability).
(CH2)n+1
OH
(37)
(38)
2.58–2.72,2.76–2.87, 3.11, s 7.30, s 14.4, br s –72.53, s
2 × m, 2 × 2H
1.59–1.71,2.38–2.48, 3.16, s 7.68, s 17.3, br s –71.16, s
2 × m, 2 × 2H; 2.58, t,
3JHH = 6.2, 2H
δH = 11.1–16.5 (=C–OH). No resonance for the methine
proton of the diketo tautomer was observed, although
according to the 19F NMR spectra it was present in low
concentration ( < 4%) (Table 6,7).
The most abundant tautomer was found to be the cis-
enol,* the structure of which was confirmed from the 19F
NMR spectra of compounds (14) and (21), by analysis of the
through-space spin–spin coupling of fluorine nuclei and the
methylene protons of the substituent in the α-position of the
β-diketone (Table 7). The shift range of the enolic protons
(Tables 5,6) is due to the presence of intramolecular
hydrogen bridges, which decrease in stability from the
cyclohexane derivatives (18–31,36,40) (δH = 15.00–16.49)
to the cyclopentane derivatives (14–17,33,35) (δH = 11.1–
13.3), similarly to the starting diketones.[12,16] This stability
difference is probably caused by the increase in O–O
distance originating from the increase in ring strain when
moving from cyclohexane to cyclopentane.[12,17] The same
argument holds for compounds (37) and (38).
The arylidene proton resonances of compounds (32) and
(34) [(Z)-configuration of arylidene C–C double bond] were
observed at δH = 6.9. The respective resonances of 4-ene-1,3-
diones (14–31,33,35,36,38,40) were found at lower field
(δH =7.5–7.8). Thiscorrelates well with the corresponding δH
value of (21) [(E)-configuration of the arylidene C–C double
bond was proved by X-ray analysis, see above], and also with
the respective literature data of related (E)-configured
* The structures of all 4-ene-1,3-diones in this paper are given in the diketo-form, since we are not sure whether the compounds synthesized by us
exist in the endo- or endo-cyclic enol tautomeric form.

Condensation of 2-Polyfluoroacylcycloalkanones with Aldehydes and DMF–DMA
161
Table 5. 1H NMR data of compounds (14–34,40)
Comp.
1H NMR δ, J(Hz)
(CH2)n+1
Ar
=C–H
RF
OH
(14)
(15)
(16)
(17)
2.9, br s, 4H
2.93, s, 4H
2.93–3.10, m, 4H
2.84–3.01, m, 4H
3.05, s, 6H; 6.65–7.40, m, 4H
3.85, s, 3H; 6.89–7.44, m, 4H
7.36–7.59, m, 6H; C6H5, =CH
7.24–7.37, m, 2H; 7.45–7.49, m, 1H;
7.54–7.59, m, 1H
7.5, br s
7.55, s
–
–
–
–
13.3, br s
12.5, br s
12.9, br s
12.7, br s
–
7.69, t, 4JHH = 2.5
(18)
(19)
(20)
1.77–1.80, m, 2H; 2.59, m, 2H;
2.76–2.80, m, 2H
1.35–1.91, m, 2H; 2.51–2.87, m, 4H
3.05, s, 6H; 6.69–6.73, m, 2H;
7.42–7.46, m, 2H
1.20, t, 3JHH = 7.1, 6H; 3.42, q,
3JHH = 7.1, 4H; 6.61–7.47, m, 4H
3.84, s, 3H; 6.93, 7.41 AB-System,
JHaHb = 8.6, 4H
7.38–7.43, m
7.28–7.48, m
1.20, t, 3JHH = 7.1, 6H; 3.42, q,
3JHH = 7.1, 4H; 6.61–7.48, m, 4H
3.85, s, 3H; 6.84–7.50, m, 4H
7.78, s
7.76, t, 4JHH = 1.8
7.76, s
–
–
–
15.73, s
15.79, s
15.40, s
1.69–1.81, m, 2H; 2.58, t, 3JHH = 5.4,
2H; 2.70–2.78, m, 2H
1.53–1.90, m, 2H; 2.54–2.84, m, 4H
1.79–1.82 m, 2H; 2.58–2.63, m, 4H
1.60–1.90, m, 2H; 2.59–2.86, m, 4H
(21)
(22)
(23)
7.80, t, 4JHH = 2.0
7.89, s
7.77, t, 4JHH = 1.8
–
15.20, s
15.00, s
16.16, s
–
6.25, tt, 2JHF = 52.8,
3JHF = 5.7
(24)
(25)
1.75–2.01, m, 2H; 2.53–3.02, m, 4H
1.66–1.81, m, 2H; 2.62–2.84, m, 4H
7.8, br s
6.24, tt, 2JHF = 52.8,
3JHF = 5.5
15.74, s
15.55, s
7.41, s
7.80, t, 4JHH = 1.8
6.25, tt, 2JHF = 53.0,
3JHF = 5.5
(26)
(27)
1.59–1.90, m, 2H; 2.57–2.84, m, 4H
1.71–1.94, m, 2H; 2.56–2.94, m, 4H
5.22, s, 1H; 6.81–7.44, m, 4H
6.50–6.57, 6.68–6.72, 2 × m, both 1H;
7.49–7.82, m, 2H, C4H3O, =CH
3.04, s, 6H; 6.66–7.80, m, 4H
3.85, s, 3H; 6.88–7.50, m, 4H
7.24–7.58, m
7.78, s
–
–
–
15.83, s
15.66, s
(28)
(29)
(30)
(31)
1.66–1.89, m, 2H; 2.54–2.84, m, 4H
1.52–1.89, m, 2H; 2.56–2.85, m, 4H
1.40–1.87, m, 2H; 2.34–2.83, m, 4H
1.69–1.82, 2.59–2.70, 2.76–2.82,
3 × m, all 2H
7.79–7.82, m
7.82, s
7.84, s
7.8, br s
–
–
–
–
16.47, s
16.1, br s
15.9, br s
16.49, s
3
3.05, s, 6H; 6.71, d, JHH = 9.2, 2H;
7.45, d, 3JHH = 9.2, 2H
(32)
1.77–1.83, m, 2H; 2.59–2.65, m, 4H
7.16–7.37, m, 4H
6.91, s
–
–
–
(33)A 2.73–2.76, 2.84–2.86, 2 × m, both 2H
6.79–6.91, m, 2H; 7.14–7.22 m, 1H;
7.43, d, 3JHH = 8.0, 1H; 10.1 br s, 1H
7.14–7.40, m, 4H
7.62, t, 4JHH = 2.3
11.1, br s
(34)
(40)
2.82–2.94, m, 4H
1.74–1.91, m, 2H; 2.53–2.93, m, 4H
6.9, br s
7.8, br s
–
–
3.04, s, 6H; 6.64–7.48, m, 4H
6.24, tt, 2JHF = 52.8,
3JHF = 5.7
16.07, s
A In (D6)-dimethylsulfoxide (DMSO).
compounds.[3,9,18] Thus, compounds(14–31,33, 35, 36,38,40)
are (E)-configured at the exo-methylene C–C double bond.
The situation for (37) is not so clear, since the signal for
the olefinic proton was observed at δH = 7.30. Since this
resonance is found at a slightly higher field for the
cyclopentane ring containing an aryl substituted 4-ene-1,3-
dione than their cyclohexane analogues (see Table 5) an (E)-
configuration is proposed for (37), as for (38).
In conclusion, ring-containing polyfluorinated 1,3-
diketones underwent a condensation reaction with al-
dehydes and dimethylformamide–dimethylacetal to give
novel 1-polyfluoroalkyl-2,4-oligomethylene-alk-4-(E)-ene-
1,3-diones, which were present in their enol form both in
solution and in the solid state. They are versatile synthons
for further syntheses of potential bioactive compounds.
There is additional confirmation for the enol form of
4-ene-1,3-diones present in the solid state from the infra red
(IR) spectra (Table 8), where broad absorptions in the 3000–
4000 cm–1 region were found, typical for hydrogen-bridged
enolic hydroxy groups.[19,20]
Experimental
Melting points are uncorrected. Mass-spectra (EI, 70 eV) were carried
out on a MAT 8200 spectrometer (Table 9). NMR spectra [standards:
TMS (1H) and CFCl3 (19F)] were recorded in CDCl3 solutions on a Tesla
BS-587A instrument operating at 80.1 MHz (1H) and 75.3 MHz (19F)
Table 6. 1H and 19F NMR data of compounds (35) and (36)
Comp.
1H NMR δ, J (Hz)
19F NMR
(CH2)n+1
2.82, s, 4H
C1H=C2H
=C3H
C6H5
OH
δ
(35)
(36)
6.89–7.12, m, 3H; 7.26–7.51, m, 3H
12.6, br s
15.14, s
–76.32, s
–73.81, s
1.72–1.84, m, 2H;
2.53–2.65 m, 4H
6.93, d, 3JHH = 15.2, 1H;
7.11, dd, 3JHH = 15.2,
3JHH = 11.2, 1H
7.28–7.42, m, 3H;
7.46–7.51, m, 2H

162
D. V. Sevenard et al.
Table 7. 19F NMR data of compounds (14–22,31,33)
Table 9. MS data (EI) of compounds (16,18,20,22,31–38)
19F NMR (major tautomer) δ, J(Hz)
Comp.
m/z (%)
Comp.
–75.03, t, 5JFH = 1.6
(16)
(18)
268 (M+, 70), 199 ([M–CF3]+, 100), 171 ([M–CF3CO]+, 6), 77
(C6H5+, 6) and other fragments
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(31)
–75.81, s
–76.26, s
–76.67, s
–73.29, s
–73.19, s
325 (M+, 100), 256 ([M–CF3]+, 49), 228 ([M–CF3CO]+, 4),
184 ([M–CF3CO–N(CH3)2]+, 3) and other fragments
312 (M+, 100), 243 ([M–CF3]+, 85) and other fragments
316 (M+, 6), 281 ([M–Cl]+, 100), 247 ([M–CF3]+, 13), 69
(CF3+, 5) and other fragments
(20)
(22)
–73.70, s
–73.93, t, 5JFH = 1.2
–74.24, s
(31)
(32)
475 (M+, 100), 256 ([M–C4F9]+, 88) and other fragments
280 (M+, 52), 211 ([M–CF3]+, 100), 183 ([M–CF3CO]+, 49)
and other fragments
–126.59, –123.64, –115.48, 3 × m, all 2F;
–82.11, t, 4JFF = 8.6, 3F
–75.21, s
(33)
284 (M+, 100), 267 ([M–OH]+, 20), 215 ([M–CF3]+, 50), 187
([M–CF3CO]+, 10), 69 (CF3+, 9) and other fragments
266 (M+, 100), 197 ([M–CF3]+, 96) and other fragments
294 (M+, 100), 225 ([M–CF3]+, 40), 77 (C6H5+, 15) and other
fragments
(33)A
(34)
(35)
A In (D6)-DMSO.
(36)
(37)
(38)
308 (M+, 100), 239 ([M–CF3]+, 28), 77 (C6H5+, 20) and other
fragments
Table 8. IR data of compounds (14,19–21,23–26,28,30,40)
235 (M+, 60), 220 ([M–CH3]+, 10), 166 ([M–CF3]+, 100), 44
((CH3)2N+, 18) and other fragments
IR, ν (cm–
)
1
Comp.
249 (M+, 80), 234 ([M–Me]+, 27), 180 ([M–CF3]+, 100), 69
(CF3+, 13), 44 ((CH3)2N+, 26) and other fragments
…
C=C–C=O
O–H O (br)
(14)
(19)
(20)
(21)
(23)
(24)
(25)
(26)
(28)
(30)
(140)
1570
1555
1560
1560
1555
1570
1580
1590
1580
1540
1540
3000–4000
3000–4000
3060–4000
3000–4000
3000–4000
3000–4000
3000–4000
3000–4000
3000–4000
3000–4000
3000–4000
c) (22,24,25,29,30,36,40): The mixture was extracted with CHCl3
(3 × 10 mL). The combined extracts were dried (MgSO4) and evapo-
rated to give a residue which was purified by column chromatography
(eluent: CHCl3) and recrystallized to afford crystals (22,24,25,29,36)
(yellow), (40) (red) and (30) as a yellow oil (Table 1).
4-Trifluoroacetyl-2,3-dihydro-1H-xanthene (32)
To a mixture of (2) (1.5 g, 7.7 mmol) and salicylaldehyde (0.9 g,
7.7 mmol) in propan-2-ol (15 mL) were added BF3·OEt2 (3 drops). The
mixture was refluxed for 10 h, then cooled, diluted with water (100 mL)
and extracted with CHCl3 (3 × 10 mL). The combined extracts were
dried (MgSO4) and evaporated to give a residue which was distilled and
recrystallized to afford (32) (0.65 g, 30%) as yellow crystals (Table 1).
19F NMR δ –75.44, s.
and a Bruker DPX-200 spectrometer operating at 200.1 MHz (1H) and
188.3 MHz (19F). IR spectra were recorded in nujol on a Specord 75 IR
spectrophotometer. Chromatography was performed on a silica gel
column (normal phase, MATREX, Grace Gmbh). 2-Polyfluoroacyl-
cycloalkanones (1,2),[21] (3,6),[11] (4),[22] (5)[23] were prepared by a
Claisen-type condensation of cyclopentanone or cyclohexanone and
alkylpolyfluoroacylates in the presence of lithium hydride in dried
benzene.[11]
3-Trifluoroacetyl-1,2-dihydrocyclopenta-[b]-chromene (34)
A mixture of (33) (0.2 g, 0.7 mmol) and conc. H2SO4 (10 mL) was
heated to 160°C for 1 h. The cooled mixture was diluted with cold water
(70 mL) and extracted with CHCl3 (3 × 10 mL). The combined extracts
were dried (MgSO4) and evaporated to give a residue which was
purified by column chromatography (eluent: CHCl3) and recrystallized
to afford (34) (0.04 g, 21%) as yellow crystals. 19F NMR δ –77.69, s.
1-[N-(p-tolyl)-amino]-2-(2,2,3,3-tetrafluoropropanoyl)cyclohexene (39)
According to ref.[11] By a condensation of (3) (10.0 g, 44 mmol) and
p-toluidine (5.4 g, 50 mmol) in toluene (150 mL) was obtained (39)
(10.5 g, 76%) as yellow crystals, m.p. 75–76°C (hexane) (Found: C,
61.1; H, 5.6; F, 23.9; N, 4.4%. Calc. for C16H17F4NO: C, 61.0; H, 5.4;
Synthesis of Compounds (37,38) (General procedure)
A mixture of (1) or (2) (10 mmol) and DMF–DMA (1.3 g, 11 mmol)
was refluxed in dry toluene (8 mL) for 2 h. The solvent was evaporated
to give a solid residue that was recrystallized to afford (37,38) as yellow
needles (Table 1).
1
F, 24.1; N, 4.4%). H NMR δ 1.56–1.68, m, 4H, CH2; 2.35, s, CH3;
2.40–2.77, m, 4H, CH2; 6.32, tt, 2JHF = 53.1 Hz, 3JHF = 5.9 Hz, CF2H;
6.95–7.22, m, C6H4; 13.33, s, NH.
Synthesis of Compounds (14–31,33,35,36,40) (General Procedure)
X-Ray Analysis of Compounds (21) and (32)
To a mixture of 1,3-diketone or (39) (5 mmol) and aldehyde (5 mmol)
in propan-2-ol (15 mL) were added BF3·OEt2 (3 drops). The mixture
was refluxed (see Table 1) then cooled and diluted with water (100 mL).
Yellow prisms of (21), suitable for X-ray diffraction investigation, were
obtained from a 1:1 hexane/CHCl3 solution. Yellow prisms of (32) were
obtained from a 1:1 hexane/acetone solution. Data was collected at
173(2) K on a Siemens P4 diffractometer with low temperature device
LT2 and graphite-monochromated Mo–Kα radiation (λ = 71.073 pm).
Details of crystal data, measurement of intensities, and data processing
are summarized in Table 2. The structures were solved by direct
methods, and full-matrix least-squares refinement was performed with
the SHELX-97 (Sheldrick, 1997) program system. All non-hydrogen
atoms were refined anisotropically. H(2), H(2a) atoms for (21) were
refined isotropically. The positions of the remaining hydrogen
atoms were calculated using a riding model. The weighting schemes
Workup Procedures
a) (15,17,20,26,27,33): The mixture was extracted with CHCl3
(3 × 10 mL), the combined extracts were dried (MgSO4) and evaporated
to give a solid residue which was recrystallized to afford products as
yellow crystals (Table 1).
b) (14,16,18,19,21,23,28,31,35): The precipitate was dried and
recrystallized to afford crystals (14) (yellow-brown), (16) (orange),
(18,31) (violet), (19,23,28) (red-violet), (21,35) (yellow) (Table 1).

Condensation of 2-Polyfluoroacylcycloalkanones with Aldehydes and DMF–DMA
163
were w–1 = σ2(Fo)2 + (0.0556P)2 + 1.0987P (21) and w–1 = σ2(Fo)2 +
[9] M. T. Cocco, C. Congiu, V. Onnis, Tetrahedron Lett. 1999, 40,
4407.
[10] D. V. Sevenard, O. G. Khomutov, M. I. Kodess, K. I. Pashkevich,
Izv. Ros. Akad. Nauk, Ser. Khim. 1999, 2, 402; Russ. Chem. Bull.
1999, 48, 400.
(0.0689P)2 + 0.1701P (32) with P = (Fo + 2Fc )/3. Crystallographic
data have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publications, CCDC 157925 (21) and CCDC
157926 (32). Copies of the data can be obtained on application to the
director, CCDC; 12 Union Road, Cambridge CB2 1EZ, UK (e-mail:
deposit@ccdc.cam.ac.uk).
2
2
[11] K. I. Pashkevich, O. G. Khomutov, D. V. Sevenard, Zh. Org.
Khim. 1998, 34, 1798; Russ. J. Org. Chem. 1998, 34, 1727;
K. I. Pashkevich, D. V. Sevenard, O. G. Khomutov, Zh. Org.
Khim. 1998, 34, 1878; Russ. J. Org. Chem. 1998, 34, 1804;
K. I. Pashkevich, D. V. Sevenard, O. G. Khomutov,
O. V. Shishkin, E. V. Solomovich, Izv. Ros. Akad. Nauk, Ser.
Khim. 1999, 2, 361; Russ. Chem. Bull. 1999, 48, 359;
K. I. Pashkevich, D. V. Sevenard, O. G. Khomutov, Izv. Ros. Akad.
Nauk, Ser. Khim. 1999, 3, 562; Russ. Chem. Bull. 1999, 48, 557;
D. V. Sevenard, O. G. Khomutov, O. V. Koryakova,
V. V. Sattarova, M. I. Kodess, J. Stelten, I. Loop, E. Lork,
K. I. Pashkevich, G.-V. Röschenthaler, Synthesis 2000, 1738.
[12] K. A. K. Ebraheem, S. T. Hamdi, A. R. Al-Derzi, Z. Naturforsch.,
A: Phys. Sci. 1989, 44, 239.
Acknowledgments
We gratefully acknowledge financial support from the
Deutsche Forschungsgemeinschaft (Grant 436 RUS 113/
445/0) and the generous gift of chemicals from Dr Karl-
Heinz Hellberg, Solvay Fluor und Derivate GmbH,
Hannover, Germany. Inge Erxleben and Dr Peter Schulze are
thanked for recording mass spectra. We also thank
Dr Lyudmila N. Bazhenova and coworkers, Institute for
Organic Synthesis, Ural Branch of the Russian Academy of
Sciences, Ekaterinburg (Russia) for carrying out elemental
analyses.
[13] S. Z. Zhu, B. Xu, J. Zhang, J. Fluorine Chem. 1995, 74, 167.
[14] K. I. Pashkevich, V. I. Filyakova, Izv. Akad. Nauk SSSR, Ser.
Khim. 1984, 3, 623.
[15] D. V. Sevenard, K. I. Pashkevich, G.-V. Röschenthaler,
unpublished results.
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