Condensation of stereoisomeric 2-acetyl-2,3-diphenyloxiranes with ethyl trifluoroacetate

Article abstract of DOI:10.1023/A:1011640101970

The reaction of E-2-acetyl-2,3-diphenyloxirane with ethyl trifluoroacetate in the presence of sodium isopropoxide leads to 3-hydroxy-2,3-diphenyl-6-trifluoromethyl-2,3-dihydro-4H-pyran-4-one. Under the same conditions Z-acetyloxirane forms 3-hydroxy-2-phe

Full text of DOI:10.1023/A:1011640101970

Chemistry of Heterocyclic Compounds, Vol. 37, No. 5, 2001
CONDENSATION OF STEREOISOMERIC
2-ACETYL-2,3-DIPHENYLOXIRANES
WITH ETHYL TRIFLUOROACETATE
V. I. Tyvorskii, A. V. Pukin, and D. N. Bobrov
The reaction of E-2-acetyl-2,3-diphenyloxirane with ethyl trifluoroacetate in the presence of sodium
isopropoxide leads to 3-hydroxy-2,3-diphenyl-6-trifluoromethyl-2,3-dihydro-4H-pyran-4-one. Under
the same conditions Z-acetyloxirane forms 3-hydroxy-2-phenyl-5-trifluoromethylfuran as a result of
retroaldol cleavage of the initial cyclocondensation product.
Keywords: E- and Z-2-acetyl-2,3-diphenyloxiranes, ethyl trifluoroacetate.
Substituted α- and γ-pyrones and also various furanones containing a
cis-stilbene fragment in the
molecule are of interest as substances susceptible to photoinitiated transformations. Such compounds exhibit
photochromic characteristics [1] and can be used in the synthesis of derivatives of phenanthrene [1-3] and
pentahelicene [4]. At the same time it is known that the introduction of perfluoroalkyl groups into pyran systems
and particularly coumarins, which have been used successfully for the generation of radiation in lasers [5-7] and
also as fluorescent markers for biochemical investigations [8, 9], leads to an increase in resistance to
photooxidation and affects the solubility and spectral characteristics of the dyes [7, 10].
We have shown that various 2-perfluoroalkyl-4H-pyran-4-ones can be obtained by the reaction of
2-acetyloxiranes with perfluoroalkanoic esters followed by dehydration of the reaction products [11]. In the
present work in order to study the applicability of this approach to the synthesis of the compounds containing
two vicinal phenyl groups we realized the condensation of the stereoisomeric 2-acetyl-2,3-diphenyloxiranes (E-,
Z-1) with ethyl trifluoroacetate.
As expected [11, 12], the reaction of the oxirane E-1 with ethyl trifluoroacetate in the presence of
sodium isopropoxide led to the hydroxydihydropyranone 2a with a yield of 80%. The relative arrangement of
the hydroxyl group and the 2-H atom in compound 2a, due to the trans-opening of the oxirane ring on the side
of the β-carbon atom in the intermediate
A, is confirmed by the significant downfield shift of the signal of this
1
(Δδ 0.93 ppm), which is typical of related systems, including
proton in the H NMR spectrum of the acetate 2b
flavanonol systems [12, 13]. The absorption bands of the carbonyl group and of the double bond conjugated
with it, observed in the IR spectrum of compound 2a at 1695 and 1640 cm-1 respectively, and also the retrodiene
fragmentation of the molecular ion, deduced from the appearance of a strong peak for the deoxybenzoin radical-
cation (m/z 196) in the mass spectrum, indicate the formation of a six-membered dihydropyran ring during
cyclization [12, 14] (Scheme 1).
__________________________________________________________________________________________
Belorussian State University, Minsk; e-mail: tyvorskii@chem.bsu.unibel.by. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 5, pp. 592-597, May, 2001. Original article submitted July 14, 1999.
540
0009-3122/01/3705-0540$25.00©2001 Plenum Publishing Corporation

Scheme 1
O
O
α
β
Ph
Ph
CF3CO2Et
CH3
AcOH
O
O
Ph
i-PrONa
–
H
Ph
CF3
H O
A
E-1
O
O
Ph
RO
Ph
H
CF3
AcCl
2a R = H
2b R = Ac
An attempt to dehydrate the hydroxypyranone 2a by the action of thionyl chloride in pyridine and also
by p-toluenesulfonic acid in boiling toluene, which was undertaken with a view to forming a cis-stilbene
fragment, did not lead to the desired result. This may be due to the cis arrangement of the hydroxy group and the
hydrogen atom of the pyran ring unfavorable for elimination [11].
In order to obtain the hydroxypyranone stereoisomeric with compound 2a we investigated the reaction
of the acetyloxirane Z-1 with ethyl trifluoroacetate. We obtained the oxirane Z-1, previously synthesized by a
four-stage method [15], with an overall yield of 79% by a simpler and more effective method from its isomer
E-1 by reaction with SnCl4 in benzene followed by cyclization of the obtained chlorohydrin 3 with sodium
methoxide. The structure and relative configuration of the asymmetric atoms of compound 3 shown in the
scheme are presented on the basis of the known cis-opening of the three-membered ring in aryl-substituted
acyloxiranes on the side of the β-C atom by the action of Lewis acids in aprotic solvents [16]. The
transformation of this product into the oxirane Z-1 in a basic medium takes place in the usual way with
1
inversion of the configuration at the halogen-bearing carbon atom [17, 18]. In the H NMR spectrum of the
oxirane Z-1 compared with the spectrum of the E-isomer the hydrogen atoms of the acetyl group are 0.12 ppm
upfield on account of the screening by the cis-located phenyl ring, the hydrogen atoms of which are
nonequivalent on account of the effect of the carbonyl group and give a multiplet signal. The singlet of the 3-H
proton is also shifted upfield by 0.27 ppm on account of the absence of the descreening effect of the acetyl
group, characteristic of the E-isomer [19].
The condensation of the oxirane Z-1 with ethyl trifluoroacetate in the presence of sodium isopropoxide
led unexpectedly to the 3(2H)-furanone 5a with a yield close to quantitative. This is the product from
at the α-C atom and subsequent retroaldolization of the obtained
cyclization of an intermediate of type A
compound 4, which was detected by TLC at the initial stages of the process but was easily converted into the
furanone 5a during an attempt at isolation. The benzaldehyde released as a result of retroaldol cleavage was
identified by means of its 2,4-dinitrophenylhydrazone (Scheme 2).
The difference in the regioselectivity of the cyclization stage in our investigated condensation of the
isomeric oxiranes E-, Z-1 has an analogy with the problem of obtaining six-membered flavanonols and five-
membered aurones in the course of the oxidation of o'-hydroxychalcones by hydrogen peroxide [the Algar–
Flynn–Oyamada (AFO) reaction] and related processes [20-22]. However, the formation of the intermediate
is probably due to steric hindrances for cyclization at the β-C atom, created in the respective
compound 4
intermediate by the phenyl group in the cis position to the acyl fragment and not by effects of the substituents in
the aromatic rings, as in the case of the AFO reaction.
541

Scheme 2
O
O
H
Ph
HO
Ph
O
H
1. SnCl4, C6H6
1. CF3CO2Et, i-PrONa
MeONa
MeOH
Me
Me
E-1
Ph
2. H2O
2. AcOH
Ph
Cl
3
Z-1
O
RO
O
Ph
– PhCHO
CF3
CF3
Ph
O
CF3
O
Ph
O
Ph
HO
AcCl, Py
5a
5b R = H
5c R = Ac
4
Compound 5a, which proved labile in air both during storage in the crystalline state and during
chromatographic isolation, exists predominantly in the tautomeric hydroxyfuran form 5b, as shown by the
1H NMR and 13C NMR spectra. In the 1H NMR spectrum the signal of the proton of the hydroxyl group appears
in the form of a broad singlet in a relatively upfield position for such systems at 4.56 ppm. This is typical of the
enolic forms of compounds in which a strong intramolecular hydrogen bond cannot form and, in particular,
3-hydroxythiophenes like compound 5b [23]. With the addition of DMSO-d6 to the solution of the hydroxyfuran
5b in deuterochloroform used for recording the spectrum the signal is strongly shifted downfield (9.5 ppm). The
13C NMR spectrum does not contain signals in the region of more than 180 ppm, specific for the carbon atoms
of the carbonyl group, and this also indicates a significant preference for the tautomer 5b. At the same time in
addition to the strong absorption band of the OH group there is a weak band at 1740 cm-1, corresponding to the
stretching vibrations of the C=O group, and in comparison with hydroxydihydropyranone 2a the carbonyl
absorption has higher frequency, which is typical of 3(2H)-furanones [24]. In order to confirm the structure of
compound 5b we obtained its more stable acetate 5c, the spectral characteristics of which agreed with published
data for related derivatives of furan: In the IR spectrum of this compound the maximum of the band for the
carbonyl absorption of the acetoxyl group is observed at 1785 cm-1, which is typical of 3-acetoxyfurans [25].
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker AC-200 spectrometer at 200 MHz (solvent
deuterochloroform, internal standard TMS) and a Tesla BS-467A spectrometer at 60 MHz (for solutions of
compounds 1 and 3 in carbon tetrachloride with HMDS as internal standard). The 13C NMR spectra were
obtained on a Bruker AC-200 spectrometer at 50.3 MHz for solutions in deuterochloroform. The chemical shifts
were measured with reference to TMS. The IR spectra were recorded on a Specord 75IR spectrophotometer in
carbon tetrachloride, and the mass spectra were obtained on a Shimadzu QP-5000 instrument (70 eV ionizing
electrons). The reactions and the purity of the obtained compounds were monitored by TLC on Silufol plates
with development with aqueous potassium permanganate solution.
E
E
-2-Acetyl-2,3-diphenyloxirane ( -1).
The compound was obtained by oxidation of E-3,4-diphenyl-3-
buten-2-one with an alkaline solution of hydrogen peroxide by the method in [15]. Yield 90%; mp 63-64°C
1H NMR spectrum, δ, ppm: 7.01 (5H, s, Ph); 6.88 (5H, s, Ph); 4.18 (1H, s, 3-H); 2.05
(aqueous methanol) [15].
(3H, s, CH3).
542

3-Hydroxy-2,3-diphenyl-6-trifluoromethyl-2,3-dihydro-4H-pyran-4-one (2a). The compound was
obtained by the condensation of acetyloxirane E-1 with ethyl trifluoroacetate by the method in [12]. Yield 80%;
mp 73.5-74°C (hexane). IR spectrum, , cm-1: 1640 (C=C), 1695 (C=O), 3495 (OH). 1
H NMR spectrum, δ, ppm:
ν
13C NMR spectrum, δ, ppm,
7.33-7.05 (10H, m, 2Ph); 6.36 (1H, s, 5-H); 5.63 (1H, s, 2-H); 4.05 (1H, bs, OH).
2
J (Hz): 194.41 (C=O); 161.19 (q, JC–F = 38, CCF3); 135.20 (Cquat, Ph); 132.38 (Cquat, Ph); 128.95 (C, Ph);
1
128.68 (C, Ph); 128.20 (2C, Ph); 127.67 (2C, Ph); 127.62 (2C, Ph); 126.16 (2C, Ph); 118.53 (q, JC–F = 275,
CF3); 104.45 (CH=CCF3); 88.92 (CHO); 76.12 (COH). Mass spectrum (m/z) (Irel, %): 335 (M+ + 1, 20), 334
(M+, 100), 229 (37), 228 (77), 196 (58), 165 (17), 131 (94), 118 (27), 105 (90), 91 (17), 90 (28), 89 (20), 77
(65), 53 (17), 51 (14). Found, %: C 64.85; H 4.13. C18H13F3O3. Calculated, %: C 64.67; H 3.92.
3-Acetoxy-2,3-diphenyl-6-trifluoromethyl-2,3-dihydro-4H-pyran-4-one (2b). The compound was
synthesized by the acylation of compound 2a with an excess of acetyl chloride [12]. Yield 81%; mp 90-91°C
(hexane). IR spectrum, , cm-1: 1645 (C=C), 1705, 1750 (C=O).
1H NMR spectrum, δ, ppm: 7.37
-6.80 (10H,
ν
m, 2Ph); 6.56 (1H, s, 2-H); 6.38 (1H, s, 5-H); 2.28 (3H, s, CH3). Found, %: C 63.99; H 4.21. C20H15F3O4.
Calculated, %: C 63.83; H 4.02.
4-Chloro-3-hydroxy-3,4-diphenylbutan-2-one (3). To a solution of acetyloxirane E-1 (4.0 g,
16.8 mmol) in dry benzene (100 ml) with stirring we added dropwise SnCl4 (4.2 ml, 36.0 mmol), while keeping
the temperature at 18-20°C. The reaction mixture was stirred for a further 2 h and poured onto ice. The benzene
layer was separated, washed with dilute hydrochloric acid and then with water, and dried with sodium sulfate.
Crystallization of the residue after removal of the benzene gave 4.0 g (87%) of chlorohydrin 3; mp 95-96°C
1H NMR spectrum, δ, ppm:
7.36-6.84 (10H, m, 2Ph); 5.77 (1H, s, CHCl); 4.03 (1H, s, OH); 2.17 (3H, s, CH3). Found, %: C 70.23; H 5.69.
(hexane–isopropanol, 5:1). IR spectrum, , cm-1: 1720 (C=O), 3425, 3545 (OH).
ν
С 69.95; Н 5.50
C16H15ClO2. Calculated, %:
.
Z
Z
-2-Acetyl-2,3-diphenyloxirane ( -1). 3
To a solution of chlorohydrin (3.0 g, 10.9 mmol) in absolute
methanol (20 ml) while stirring and cooling with iced water we added dropwise a solution of sodium methoxide,
obtained from sodium (0.25 g, 10.9 mmol) and absolute methanol (25 ml). After stirring for 3 h methanol was
evaporated at reduced pressure, water (5 ml) was added to the residue, and the mixture was extracted with
methylene chloride. The extract was washed with water and dried with sodium sulfate. The methylene chloride
was distilled, and 2.3 g (89%) of oxirane Z-1 was obtained by crystallization of the residue; mp 70°C (hexane)
H NMR spectrum, δ, ppm: 7.57-7.06 (5H, m, Ph); 7.17 (5H, s, Ph); 3.91 (1H, s, 3-H); 1.93 (3H, s, CH
[15]. 1
3).
3-Hydroxy-2-phenyl-5-trifluoromethylfuran (5b). To a solution of sodium isopropoxide,
obtained from sodium (0.23 g, 10 mmol) and absolute isopropyl alcohol (7 ml) we added absolute diethyl ether
(35 ml). With vigorous stirring we then added dropwise a solution of oxirane Z-1 (1.2 g, 5 mmol) and ethyl
trifluoroacetate (1.2 ml, 10 mmol) in ether (5 ml), while keeping the temperature between -10 and
-12°C (cooling with ice and salt). The reaction mixture was stirred for 6 h, neutralized to pH 6-7 with acetic
acid, kept at 18-20°C for 5 h, and washed with water. The ether layer was extracted with a saturated solution of
NaHSO3 until the smell of benzaldehyde had disappeared (monitored by TLC, development with an
alcohol solution of 2,4-dinitrophenylhydrazine in the presence of sulfuric acid), washed again with water, and
dried with sodium sulfate. After evaporation of the ether we obtained 1.1 g (95%) of furan 5b; mp 96-97°C
1H NMR spectrum, δ, ppm,
13C NMR spectrum, δ, ppm,
(carbon tetrachloride). IR spectrum, , cm-1: 1635 (C=C), 1745 (C=O), 3595 (OH).
ν
J, Hz: 7.83-7.25 (5H, m, Ph); 6.64 (1H, q, JH–F = 1.0, 4-H); 4.56 (1H, br. s, OH).
2
J, Hz: 141.47 (COH); 137.17 (q, JC–F = 43, CCF3); 130.10 (C–Ph); 128.50 (2C, Ph); 127.05 (Cquat, Ph);
1
126.50 (C, Ph); 123.33 (2C, Ph); 119.19 (q, JC–F = 266, CF3); 108.22 (CH=CCF3). Mass spectrum, m/z
(Irel, %): 228 (M+, 100), 131 (41), 105 (42), 103 (23), 90 (19), 89 (21), 77 (81), 75 (14), 69 (21), 57 (23),
53 (35), 51 (48), 50 (23), 44 (45), 43 (62), 41 (31). Found, %: C 58.11; H 3.29. C11H7F3O2. Calculated, %:
C 57.90; H 3.09.
543

In a similar experiment the reaction mixture, obtained from oxirane Z-1 (0.3 g, 1.3 mmol) without
treatment with NaHSO3 solution, was chromatographed on a column of silica gel with chloroform as eluent.
Benzaldehyde was obtained, and its treatment with an excess of an alcohol solution of
2,4-dinitrophenylhydrazine in ethanol in the presence of sulfuric acid gave 0.2 g (56%) of benzaldehyde
2,4-dinitrophenylhydrazone; mp 233°C [26]. We also obtained 0.19 g (66%) of hydroxyfuran 5b.
3-Acetoxy-2-phenyl-5-trifluoromethylfuran (5c). To a solution of hydroxyfuran 5b (0.28 g,
1.2 mmol) in dry pyridine (1 ml) while stirring and cooling with iced water we added dropwise acetyl chloride
(0.18 ml, 2.5 mmol). After stirring for 2 h the reaction mixture was decomposed by the addition of water (5 ml)
and extracted with methylene chloride. The extract was washed with water and dried with sodium sulfate. The
residue after removal of the solvent was chromatographed on a column of silica gel with a 3:1 mixture of hexane
and ether as eluent. We isolated 0.23 g (69%) of acetate 5c; mp 36°C (pentane). IR spectrum, , cm-1: 1635
ν
1H NMR spectrum, δ, ppm:
(C=C), 1785 (C=O).
7.78-7.26 (5H, m, Ph); 7.06 (1H, s, 4-H); 2.35 (3H, s, CH3).
2
13C NMR spectrum, δ, ppm,
J, Hz: 167.70 (COCH3); 143.17 (C–OCOCH3); 138.40 (q, JC–F = 43, CCF3); 134.10
1
(C–Ph); 128.86 (2C, Ph); 128.74 (C, Ph); 128.18 (Cquat, Ph); 124.89 (2C, Ph); 118.93 (q, JC–F = 267, CF3);
110.04 (q, JC–F = 2, CH=CCF3); 20.92 (COCH3). Mass spectrum, m/z (Irel): 270 (M+, 9), 229 (14), 228 (100),
3
227 (20), 131 (14), 105 (18), 77 (19), 51 (8), 43 (19). Found, %: C 57.98; H 3.57. C13H9F3O3. Calculated, %:
C 57.79; H 3.36.
REFERENCES
1.
2.
3.
4.
5.
6.
G. Rio and J. C. Hardy, Bull. Soc. Chim. France, 3578 (1970).
N. Ishibe, M. Sunami, and M. Odani, J. Am. Chem. Soc., 95, 463 (1973).
N. Ishibi, S. Yukata, J. Masui, and Y. Ishida, Chem. Commun., No. 7, 241 (1975).
A. A. Frimer, J. D. Kinder, W. J. Youngs, and M. A. B. Meador, J. Org. Chem., 60, 1658 (1995).
S. Kumar, R. Giri, S. C. Mishra, and M. K. Machwe, Indian J. Pure Appl. Phys., 33, 431 (1995).
A. V. Kropachev, A. Ya. Il'chenko, V. I. Popov, and L. M. Yagupol'skii, Ukr. Khim. Zh., 54, 1078
(1988).
7.
8.
9.
10.
11.
E. J. Schimitschek, J. A. Trias, M. Taylor, and J. T. Celto, IEEE J. Quantum Electronics, 9, 781 (1973).
A. N. Markaryan and Ya. V. Voznyi, Bioorg. Khim., 16, 569 (1990).
E. R. Bissell, A. R. Mitchell, and R. E. Smith, J. Org. Chem., 45, 2283 (1980).
T. Kirrane and W. J. Middleton, J. Fluor. Chem., 62, 289 (1993).
V. I. Tyvorski, D. N. Bobrov, O. G. Kulinkovich, N. De Kimpe, and K. A. Tehrani, Tetrahedron, 54,
2819 (1998).
12.
13.
14.
V. I. Tyvorskii, L. S. Stanishevskii, and I. G. Tishchenko, Khim. Geterotsikl. Soedin., 897 (1978).
H. Wagner, O. Seligmann, M. Seitz, and D. Abraham, Z. Naturforsch., 31B, 876 (1976).
V. I. Tyvorskii, I. G. Tishchenko, and V. P. Suboch, Izv. Akad. Nauk BSSR. Ser. Khim. Nauk, No. 6, 62
(1981).
15.
16.
17.
18.
19.
H. E. Zimmermann, L. Singer, and B. S. Thyagarajan, J. Am. Chem. Soc., 81, 108 (1959).
L. Reichel and A. Neubauer, Lieb. Ann. Chem., 7/8, 1538 (1975).
L. Reichel and A. Neubauer, Z. Chem., 8, 423 (1968).
H. H. Wassermann and N. E. Aubrey, J. Am. Chem. Soc., 78, 1726 (1956).
D. D. Keane, W. I. O'Sullivan, E. M. Philbin, R. M. Simons, and P. C. Teague, Tetrahedron, 26, 2533
(1970).
20.
W. P. Cullen, D. M. X. Donnelly, A. K. Keenan, P. J. Keenan, and K. Ramdas, J. Chem. Soc. Perkin
Trans. 1, 1671 (1975).
21.
T. R. Cormley and W. I. O'Sullivan, Tetrahedron, 29, 369 (1973).
544

22.
23.
24.
25.
26.
J. A. Donnelly, M. J. Fox, and T. C. Sharma, Tetrahedron, 35, 1987 (1979).
R. Lantz and A. B. Hörnfeldt, Chem. Scr., 2, 9 (1972).
V. Ya. Sosnovskikh, M. Yu. Mel'nikov, and V. A. Kutsenko, Izv. Akad. Nauk. Ser. Khim., 1553 (1997).
R. Lantz and A. B. Hörnfeldt, Chem. Scr., 10, 126 (1976).
R. Shriner, R. Fuson, D. Curtin, and T. Morrill, Identification of Organic Compounds [Russian
translation], Mir, Moscow (1983), p. 607.
545