Mendeleev Communications Electronic Version, Issue 6, 1999 (pp. 213–255) Trifluoroacetylation of O-vinyl acetoxime Boris A. Trofimov,* Elena Yu. Schmidt, Al’bina I. Mikhaleva, Alexander M. Vasil’tsov, Ludmila I. Larina and Ludmila V. Klyba Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russian Federation. Fax: +7 3952 39 6046; e-mail: bat@irioch.irk.ru O-Vinyl acetoxime reacts with trifluoroacetic anhydride (pyridine, room temperature) to form (E)-O-[2-(trifluoroacetyl)vinyl] acetoxime or 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1,2-oxazole.Vinyl ethers,1 N-vinyl amides1 and vinyl sulfides2,3 are known to be capable of undergoing the non-typical (for ordinary alkenes) electrophilic substitution at the b-vinylic carbon when treated with trifluoroacetic or trichloroacetic anhydrides.Note that under similar conditions, N-vinylpyrroles are trifluoroacetylated normally at the a-position of the pyrrole ring retaining their N-vinyl group intact.4,5 Despite its extraordinary nature, synthetic and mechanistic importance, this type of vinylic electrophilic substitution still has not got the attention it deserves. This note is a preliminary communication on the trifluoroacetylation of currently available6,7 O-vinyl oximes, representing the first example of electrophilic substitution at the vinyl group adjacent to two directly linked heteroatoms, CH2=CHON, wherein the basic nitrogen can be concurrently attacked by an electrophile.We found that O-vinyl acetoxime 1 reacts readily with trifluoroacetic anhydride in the presence of pyridine at room temperature to give expected1–3 (E)-O-[2-(trifluoroacetyl)vinyl] acetoxime 2 after direct distillation in 53% yield (not optimised yield) along with pyridinium trifluoroacetate 3 and incompletely reacted pyridine–trifluoroacetic anhydride complex 4.However, when the reaction mixture is treated with aqueous NaHCO3, 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1,2-oxazole 5 is isolated as the only product in 65% yield (Scheme 1).The structure of oxazole 5 follows from the 1H, 13C, 19F and 15N NMR spectra as well as from the fragmentation under electron ionization.† The chemical shift of 15N (–6.41 ppm) corresponds to the 1,2-oxazole structure (–12.0 to 2.2 ppm).8,9 In the IR spectrum of a dilute solution of oxazole 5 in CCl4 (0.001 M), only a narrow symmetric band at 3577 cm–1 is present in the region 3000–3700 cm–1.This band can be attributed to the following intramolecular H-bond: The similar H-bonding was observed earlier10 in 2,6-difluorophenol (nOH = 3586 cm–1). The formation of 5 implies the hydrolysis of 2 via intermediate semi-acetal-like adduct 6 which decomposes to 3-oxo- 4,4,4-trifluorobutyraldehyde 7 and acetoxime 8.The two latter compounds undergo reoximation to result in corresponding aldoxime 9 and acetone (the hydroxylamine exchange between oximes and aldehydes or ketones under solvolytic conditions is a well-established fact11). The intramolecular hydroxyl–carbonyl interaction in aldoxime 9 leads to the ring closure with the formation of oxazole 5 (Scheme 2).Similar compounds, 5-amino-5-trifluoromethyl-3-substituted- 4,5-dihydro-1,2-oxazoles (D2-isoxazolines), have been recently synthesised by an entirely different reaction from 2-amino-2- trifluoromethyl-5,5-dimethyltetrahydro-4-pyrones and hydroxylamine. 12 Thus, the perfluoroacylation of O-vinyl oximes promises to become a source of highly reactive perfluoroalkyl-substituted ketoaldehydes and 1,2-oxazole derivatives, new potent building blocks for the design of biologically active molecules.While the trifluoroacetylation of O-vinyl oximes originates a novel class of multifunctional compounds, the cyclization of trifluoroacetyl acetaldoxime is a useful supplement to the wellknown syntheses12–14 of 4,5-dihydro-1,2-oxazoles (apart from † 1H NMR (400.13 MHz), 13C NMR (101.61 MHz) in CDCl3, standard TMS; 19F NMR (89.35 MHz) in CDCl3, standard CCl3F; 15N NMR (40.56 MHz) in [2H6]DMSO, standard MeNO2.To a mixture of 1.98 g (20 mmol) of O-vinyl acetoxime 1 and 1.58 g (20 mmol) of pyridine in 15 ml of diethyl ether, 4.2 g (20 mmol) of trifluoroacetic anhydride was added dropwise for 1.5 h. (a) Upon distillation of the reaction mixture in a vacuum, 2.07 g of oxime 2 (yield 53%) was isolated, bp 60–63 °C (2 mmHg). 1H NMR, d: 8.21 (d, H-2, 3J2–3 12.3 Hz), 6.18 (d, H-3, 3J2–3 12.3 Hz), 2.02, 2.00 (Me2). 13C NMR, d: 180.36 (C=O, 2JC–F 35.1 Hz), 166.91 (C-2), 163.89 (C-4), 116.53 (CF3, 1JC–F 290.6 Hz), 97.80 (C-3), 21.47, 16.73 (Me2). 19F NMR, d: –78.73. IR (neat, n/cm–1): 571, 536, 582, 595, 683, 700, 726, 752, 826, 898, 972, 1055, 1145, 1195, 1257, 1279, 1308, 1371, 1435, 1598, 1650, 1688, 1711, 1793, 2852, 2926, 2964, 3001, 3052, 3086.Found (%): C, 42.99; H, 4.56; N, 7.20; F, 28.67. Calc. for C7H8F3NO2 (%): C, 43.08; H, 4.13; N, 7.18; F, 29.21. (b) The reaction mixture was poured into 30 ml of a saturated aqueous NaHCO3 solution. The organic layer was separated, and the aqueous layer was extracted with diethyl ether (4×5 ml).The combined extract was washed with water (3×5 ml) and dried over MgSO4. After the removal of ether and vacuum sublimation (1 mmHg) of the residue, 2.01 g (65%) of oxazole 5 was obtained, mp 41–42 °C. 1H NMR, d: 7.30 (nr. m, H-3, 3J3–4 1.7 Hz, 3J3–4' 1.5 Hz, 5JH–F 0.8 Hz), 3.72 (br. s, OH), 3.37 (dq, H-4, 2J4–4' 18.8 Hz, 3J3–4 1.7 Hz, 4JH–F 0.5 Hz), 3.18 (dq, H-4', 2J4–4' 18.8 Hz, 3J3–4' 1.5 Hz, 4JH–F 1.5 Hz). 13C NMR, d: 146.58 (C-3, 1J3–4 34.8 Hz), 121.99 (CF3, 1JC–F 283.7 Hz), 101.59 (C-5, 2JC–F 34.9 Hz, 1J4–5 41.8 Hz), 43.65 (C-4, 1J3–4 34.8 Hz, 1J4–5 41.8 Hz). 19F NMR, d: –83.65. 15N NMR, d: –6.41 (2JN–H 15.8 Hz). IR (KBr, n/cm–1): 451, 471, 534, 576, 602, 700, 734, 800, 840, 886, 924, 980, 1010, 1057, 1130, 1182, 1199, 1256, 1304, 1330, 1416, 1430, 1628, 2861, 2930, 2957, 2991, 3100, 3577 (OH in CCl4).MS, m/z (%): 155 (1.8, [M+]), 138 (6.1, [M – OH+]), 125 (14.7), 111(14), 97 (12.5, [CF3CO+]), 92 (14.7), 86 (100), 69 (36.1), 68 (19.8), 67 (8.4), 63 (17.5), 58 (21.6), 56 (19.3), 54 (15.3), 44 (22.7), 42 (61.3). Found (%): C, 30.65; H, 3.06; N, 8.51; F, 36.67. Calc. for C4H4F3NO2 (%): C, 30.18; H, 2.52; N, 8.81; F, 36.77.Me N Me O Me N Me O F3C O pyridine 1 N N H CO2CF3 · O(COCF3)2 2 3 4 1 2 3 4 NaHCO3/H2O N O H3 H4' H4 OH CF3 5 Scheme 1 + (CF3CO)2O N O O H C F F FMendeleev Communications Electronic Version, Issue 6, 1999 (pp. 213–255) the above procedure,12 also through the 1,3-dipolar addition of nitrile oxides to alkenes13 and oximation of a,b-ethylenic carbonyl compounds14).References 1 M. Hojo, R. Masuda, Y. Kokuryo, H. Shioda and S. Matsuo, Chem. Lett., 1976, 499. 2 M. Hojo, R. Masuda and Y. Kamitori, Tetrahedron Lett., 1976, 1009. 3 M. Hojo and R. Masuda, J. Org. Chem., 1975, 40, 963. 4 B. A. Trofimov and A. I. Mikhaleva, N-Vinilpirroly (N-Vinylpyrroles), Nauka, Novosibirsk, 1984, p. 127 (in Russian). 5 B.A. Trofimov, in Pyrroles, Part Two: The Synthesis, Reactivity and Physical Properties of Substituted Pyrroles, ed. R. A. Jones, Wiley, New York, 1992, p. 131. 6 B. A. Trofimov, A. I. 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Me N Me O F3C O 2 H2 O OH 6 O F3C O 7 NOH Me Me 8 NOH F3C O 9 O Me Me Scheme 2 5 Received: 25th May 1999; Com. 99/1490