uPolyhalogenated heterocyclic compounds. Part 41 Cycloaddition mreactions involving hexafluorobut-2-yne and l,l,l,2,4,4,4-IIheptafluorobut-2-ene 7i-zRichard D. Chambers,* Alex J. Roche and Michael H. Rock Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, UK Cycloadducts, formed by addition of hexafluorobut-2-yne, may be transformed into bis(trifluoromethy1)-benzene,-phenol and -furan derivatives. Tetrakis(trifluoromethy1)benzenemay also be produced. Heptafluorobut-Zene 2 is also a very efficient dienophile for reactions with cyclopentadiene and furan. Reaction of 2 with furan derivatives at elevated temperatures gives a very effective 'one pot' synthesis of 3,4-bis(trifluoromethyl)furan derivatives. Other workers lP6 have demonstrated that hexafluorobut-2-yne 1 is an excellent synthon for introducing two trifluoromethyl groups into furan or benzenoid systems, through initial cycloaddition reactions, followed by various ring-opening procedures on the products (see later for examples from our own work).Hexafluorobut-2-yne 1 could be accessible, but currently it is either very expensive to purchase or unattractive to make in the laboratory because the most efficient procedure involves anhydrous hydrogen fluoride.' In contrast, 1,1,1,2,4,4,4-heptafluorobut-2-ene2 is relatively easy to make in the laboratory, from hexachlorobuta-l,3-dieneand potas- sium fluoride,' and we have recently shown that hexafluoro- but-2-yne 1 can be obtained from 2.9In this paper, we describe further use of hexafluorobut-2-yne 1 for introduction of trifluoromethyl groups into aromatic systems, but we also demonstrate for the first time the direct use of 2 in cycloadditions, without the need to form the butyne 1 as an intermediate.Some of these reactions have been remarkably successful, and one-step procedures have been developed for bis(trifluorome t hy1)furan derivatives. Results and discussion Hexafluorobut-2-yne 1 reacts readily with furan and its derivatives to give cycloaddition products,' and Scheme 1 shows further examples of this process. Moreover, we have shown that these cycloaddition products may be further transformed to bis(trifluoromethy1)furan derivatives, first by selective reduction of the unsubstituted double bond, followed by pyrolytic elimination of ethene.We have also shown that the cycloadducts may be transformed into bis(trifluoromethy1)- benzene derivatives by reaction with a low-valent titanium reagent (titanium tetrachloride-lithium aluminium hydride- triethylamine), and also into phenol derivatives by the action of boron trifluoride-diethyl ether complex. Further examples of compounds that we have produced by this methodology include 9-16, and therefore hexafluorobut-2- yne 1 is a potentially useful 'building block' for the synthesis of a variety of molecules containing two trifluoromethyl groups. We now find, however, that more easily accessible' heptafluorobut-2-ene 2 participates easily in cycloaddition reactions to both furan and cyclopentadiene, and the reaction temperatures required are comparable to those used for hexa- fluorobutyne 1.Examples are shown in Scheme 2. Characteris- ation of the geometric isomers of 17a and 17b, and 18a and 18b was possible on the basis of their 'H NMR spectra, where coupling of the bridgehead hydrogen to the adjacent CHCF, site depends on the dihedral angle (Karplus rule"). For the isomer with the hydrogen in the em position, J values are of li F3Ce CF3 1 + amp;Me i+amp;cF3-0 QCF3 CF3 Me 6 CF3 Me 7liv Scheme 1 Reagents and conditions: i, 100-200 "C; ii, TIC,-LiAIH,-Et,N; iii, BF, Et,O; iv, H,-Pt/C; 400 "C amp;CF3 X CF, 9 X=H, Y=CH,OH 10 X=CH,OH, Y=CH,OH 11 X=H, Y=Br xfiy F3C CF3 14 X=H, Y=CH,OH 15 X=CH,OH, Y=CH,OH 12 X=H, Y=CH,OH 13 X=CH,OH, Y=CH,OH @F3 CF3Y 16 X=H, Y=CH,OH the order of 4Hz, while for the corresponding endo hydrogen, the values were approximately zero.Adducts 17a and 17b, and 18a and 18b reacted with potassium tert-butoxide, and diene 20 resulted from 18a and J. Chem. SOC.,Perkin Trans. 1,1996 1095 X XF3cwH+ amp; -+HCF, amp;pF3 F CFS F* H 2 X=O, CH2 CF3 CF3 17b X=O (39) 17a X=O (38) 18b X=CH, (33y0)1 18a X=CH, (33) 1ii X Scheme 2 Reagents and condirions: i, 120 "C, 8 h; ii, Bu'OK, Bu'OH, reflux Table 1 Reaction of 2 with furan, effect of temperature Product () Conditions 7',T 17a, 17b 19 3 U 120 78 --h 150 5 19 -c 150 8 4 d 200 __ ~ 25 --70e 300 a Carius tube, agitated by horizontal rotation, for 4 d.Quartz tube (cu. 5 cm3 volume), no agitation. ' As a, but with water as solvent. Rocked sealed metal tube, 1 week. 'Rocked sealed metal tube, 8 h. Table 2 Synthesis of 3,4-bis(trifluoromethyl)furan derivatives Starting furan Product furan X Y T/"C X Y Compound Yield () H H 300 H H 3 70 Me Me 200 Me Me 21 61 H CN 250 H CN 22 71 H H 3 21 H C0,H 300 H H 3 39 H C0,Me 250 H C0,Me 23 85 H C0,Et 250 H C0,Et 24 89 H CHO 225 H CHO 25 51 18b. However, an intractable tar resulted from 17a and 17b, and characterisation could not be made. It seems reasonable to conclude, therefore, that opening of the oxygen bridge occurs in 19, followed by a polymerisation process.We noted in the product mixture from the reaction of 2 with furan a small amount of the product of dehydrofluorination 19, and therefore, we explored the effect of reaction temperature on the product range (Table 1). Indeed, the percentage of diene 19 increased at first with increasing temperature, but we also noted that at 200 OC, bis(trifluoromethy1)furan 3 was also present. This encouraged further investigation of temperature and, quite remarkably, at 300 "C,3 was not only the sole product, but also present in 70 yield. Therefore, this constitutes a useful 'one- pot' synthesis of 3. Table 2 demonstrates that this process may also be applied to some furan derivatives, and 2-ethyl furanoate is particularly effective.In contrast, decarboxylation occurred starting with 2- furoic acid, but the corresponding product 26 was obtained indirectly by the basic hydrolysis of the ester derivatives 23 and 24. 1096 J. Chern. SOC., Perkin Trans. 1, 1996 QF3cp ,373 F3C CF3F3C 27a 27b 27c Table 3 Attempted syntheses of bis(trifl uoromethy 1)cyclopenta- dienes Products () T/"C 18a, 18b 20 27a-c 400 40 450 6 18 6 500 7 17 5 The reaction pathway in these 'one-pot' reactions clearly involves the cycloadducts formed from heptafluorobutene 2, rather than possible preliminary thermal elimination of hydrogen fluoride from 2 giving 1, followed by cycloaddition to furan (Scheme 3). This follows from the observation that no 2 17a, b-19 --+ 3 Scheme 3 significant formation of 1 results from the heating of 2 under equivalent conditions.We investigated corresponding approaches to 'one-pot' procedures for the synthesis of bis( trifluoromethy1)- cyclopentadiene 27 and derivatives, but up to 200"C, little elimination of hydrogen fluoride occurred from 18a and 18b, and at higher temperatures, only low yields of diene 20 were obtained. The difficulty does not rest solely with the stage involving the elimination of hydrogen fluoride because the pyrolysis of diene 20 at 30 "C gave none of cyclopentadiene 27, although small amounts of 27a-27c were obtained at even higher temperatures (Table 3). We can attribute the difference between formation of furan 3 and 27 as being due to the driv- ing force for formation of an aromatic molecule in the case of 3.Experimental 'H NMR spectra were recorded on a Bruker AC250 spectrometer operating at 250.13 MHz, a Varian Gemini VXR200 spectrometer operating at 199.98 MHz or a Varian VXR400S spectrometer operating at 399.96 MHz. I9F NMR spectra were recorded on the Bruker AC250 spectrometer operating at 235.34 MHz or on the Varian VXR400S spectrometer operating at 376.29 MHz. 13C spectra were recorded on the Varian VXR400S spectrometer operating at 100.58 MHz, or the Varian Gemini VXR200 spectrometer operating at 50.29 MHz. All spectra were recorded with Me,Si and fluorotrichloromethane as internal references. J Values are given in Hz.GLC-MS mass spectra were recorded on a Fisons Trio 1000 spectrometer linked to a Hewlett Packard 5890 series I1 gas chromatograph fitted with a 20 m cross-linked methyl silicone capillary column. All GLC-MS mass spectra were generated by electron impact. FAB mass spectra were recorded using a VG7070E spectrometer, and glycerol as a solvent. FTIR spectra were recorded on a Perkin-Elmer 1600 series FTIR spectrometer. Solid samples were run as KBr discs, liquid samples were run as thin films between KBr plates, and volatile samples were run in a gas cell fitted with KBr plates. Ether refers to diethyl ether and petrol refers to light petroleum (bp 40-60 "C). Synthesis of 2,3,5,6-tetrakis(trifluoromethyl)-7-oxabicyclo-2.2.1 hepta-2,5-diene4 A mixture of 3,4-bis(trifluoromethyl)furan 3 (3.0 g, 0.017 mol) and hexafluorobut-2-yne 1 (3.35 g, 0.02 mol) was heated at 100 "C in a rocking furnace for 6 h.The resulting crude white solid was sublimed (50deg;C oil bath temperature) to produce 2,3,5,6-tetrakis(triJEuoromethyl)-7-oxubicyclo2.2.lhepta-2,5-diene' 4 (5.12 g, 85) (Found: C, 32.5; F, 62.5. Calc. for C,,H,F,,O: C, 32.7; H, 0.005;F, 62.3); v,,,/cm 3050, 1700, 1350, 1275, 1200-1 100 and 1050; 6,(250 MHz; CDCl,) 5.65 (s, CH); 6,(235 MHz; CDCI,) -63.4 (s, CF,); m/z 366 (M', 19), 204 (100) and 69 (95). Synthesis of 1,2,4,5-tetrakis(trifluoromethyl)benzene 5 Tetrahydrofuran (1 00 cm3) was added to titanium tetrachloride (10 cm3, 0.60 mol) at 0 "C, with stirring, under an atmosphere of dry nitrogen.To this suspension lithium aluminium hydride (0.27 g) and triethylamine (1.6 g, 0.19 mol) were added separ- ately. After heating at reflux for 15 min, the reaction was allowed to cool to room temperature before 2,3,5,6-tetrakis- (trifluoromethyl)-7-oxabicyclo2.2.lhepta-2,5-diene 4 (2.0 g, 0.006 mol) was added. Once the addition was completed the reaction was stirred at room temperature for 48 h, then poured into water (40 cm3) and extracted with dichloromethane. The dichloromethane solution was dried (MgSO,) and evaporated. Sublimation of the crude solid (60deg;C oil bath temperature) gave 1,2,4,5-tetrakis(trifluorornethyl)benzene" 5 (1.3 g, 60) (Found: C, 35.5; F, 64.8. Calc. for C,,H,F,,: C, 34.3; H, 0.005; F, 65.1); v,,,/crn-l 3010, 1350-1250, 1200-1075, 900 and 750; 6,(250 MHz; CDCl,) 8.5 (s, CH); 6,(235 MHz; CDCl,) -59.5 (s, CF,); m/z 350 (M+, 3773, 201 (100) and 69 (35).Synthesis of l-methyl-2,3-bis(trifluoromethyl)-7-oxabicyclo-2.2.1 hepta-2,Miene 6 A mixture of 2-methylfuran (8.4 g, 0.1 mol), 1 (16 g, 0.1 mol) and tetrahydrofuran (14 g) was heated at 130 "C in a rocking furnace for 24 h. Excess 1 was removed under vacuum (100 mmHg) to leave a liquid (38.1 g). This liquid was distilled to give 1-methyl-2,3-bis(trz~para;uoromethyl)-7-oxubicyclo2.2.l-hepta-2,5-diene 6 (21.1 g, 8673, bp 118 "C at 760 mmHg (Found: C, 44.5; H, 2.45; F, 47.1. Calc. for C,H,F,O: C, 44.2; H, 2.45; F, 46.7); vmax/cm-l 3000, 1700, 1400, 1375-1100, 950, 850 and 700-600; SH(250 MHz; CDCl,) 2.00 (3 H, S, CH,), 5.66 (1 H, s, 4-CH), 7.20 (1 H, s, 5-CH) and 7.30 (1 H, s, 6-CH); 6,(235 MHz; CDCl,) -62.23 (3 F, s, 2-CCF,) and -63.37 (3 F, s, 3-CCF3);m/z 244 (M', 19) and 218 (100).Synthesis of 1-methyl-2,3-bis(trifluoromethyl)-7-oxabicyclo-2.2. I hept-2-ene 1-Methyl-2,3-bis(trifluoromethyl)-7-oxabicyclo2.2.1hepta-2,5-diene (21.0 g, 0.086 mol) was dissolved in tetrahydrofuran (100 cm3) and hydrogenated in the presence of a platinum catalyst on activated carbon (0.1 g) in a Parr apparatus. The hydrogen uptake ceased sharply after the consumption of one equivalent of hydrogen. The reaction mixture was filtered through a bed of Celite and distilled to yield l-methyl-2,3- bis(trz~uoromethyl)-7-oxabicyclo2.2.lhept-2-ene(19.8g, 9373, bp 104deg;C at 50 mmHg (Found: C, 43.9; H, 3.2; F, 47.1.C,H,F,O requires C, 43.9; H, 3.25; F, 46.7); vmax/cm-l 3000- 2950,I700,1400,1375-1100,900and 775; 6,(250 MHz; CDCl,) 1.70 (3 H, s, CH,), 1.90 (2 H, s, CH,), 2.10 (2 H, s, 6-CH2) and 5.70 (1 H, S, 4-CH); 6,(235 MHz; CDCl,) -59.83 (3 F, S, 2-CCF3) and -60.71 (3 F, s, 3-CCF3); ml-7 218 (M' -28, 100) and 149 (40). Synthesis of 2-methyl-3,4-bis(trifluoromethyl)furan8 1-Methyl-2,3-bis(trifluoromethyl)-7-oxabicyclo2.2.1hept-2-ene (20.0 g, 0.05 mol) was passed dropwise through a glass tube packed with glass wool at 400 "C in a slow current of nitrogen. Volatile material was collected in a trap maintained at -78 "C and was distilled to give 2-methyl-3,4-his( trzj!uoromethyl)furan 8 (10.5 g, 96), bp 88 "C at 760 mmHg (Found: C, 38.8; H, 2.0; F, 52.7.C,H,F,O requires C, 38.6; H, 1.8; F, 52.3); v,,,/cm-' 3100, 1600, 1450, 1250-1 100, 950 and 800-700; 6,(250 MHz; CDCl,) 2.41 (3 H, s, CH,) and 7.60 (1 H, s, CH); 6,(235 MHz; CDC1,) -57.57 (3 F, s, 4-CCF3) and -60.00 (3 F, s, 3-CCF3); m/z 218 (M', 100). Synthesis of 4-methyl-2,3-bis(trifluoromethyl)phenol7 A mixture of l-methyl-2,3-bis(trifluoromethyl)-7-oxabicyclo-2.2.1hept-2,5-diene 6 (1 .O g, 0.04 mol) and boron trifluoride- diethyl ether complex (0.05 mol) was stirred at room temper- ature for 3 h, then neutralised with aqueous potassium carb- onate and extracted with ether. The ether layer was dried (MgSO,) and evaporated under reduced pressure to leave an orange solid (0.71 g).Sublimation (100 "C oil bath temperature) gave 4-methyl-2,3-bis(trfluorornethyl)phenol7 (0.58 g, 64) (Found: C, 44.4; H, 2.1; F, 46.7. C9H,F,0 requires C, 44.25; H, 2.4; F, 46.7); vmax/crnp1 3600-3100,2975-2800,1800,1650 and 1500-1 100; 6,(250 MHz; CDC1,) 2.48 (3 H, s, CH,), 7.33 (2 H, br, CH and CH) and 9.80 (1 H, br, OH);6,(235 MHz; CDCI,) -53.70 (3 F, s, 2-CCF3) and -55.00 (3 F, s, 3-CCF3); m/z 244 (M', 100) and 196 (63). Synthesis of l-(hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxa-bicyclo2.2.13 hepta-2,5-diene 9 A mixture of 2-(hydroxymethy1)furan (10.0 g, 0.1 mol), hexa- fluorobut-2-yne 1 (16.0 g, 0.1 mol) and tetrahydrofuran (14 g) was heated at 130 "C in a rocking furnace for 24 h.Excess 1 was removed under vacuum (100 mmHg) to leave a liquid (40.0 g), which was distilled to give 1-(hydroxymethyl)-2,3-bis(tri~uoromethyl)-7-oxabicyclo2.2.lhepta-2,5-diene9 (23.9 g, 92), bp 142 "C at 760 mmHg (Found: C, 41.2; H, 2.1; F, 44.4. C,H,F,O, requires C, 41.5; H, 2.3; F, 43.9); vmax/cm-i 3600-3100, 1625, 1375-1100, 900 and 700; 6,(250 MHz; CDCl,) 3.00 (1 H, br, OH), 4.23 (2 H, s, CH,), 5.61 (1 H, s, 4-CH), 7.08 (1 H, s, 5-CH) and 7.21 (1 H, s, 6-0; 6,(235 MHz; CDCI,) -62.54 (br, CF,); m/z 260 (M', 2) and 182 (100). Synthesis of 1-(hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxa-bicyclo2.2.1 hept-Zene 12 1-(Hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxabicyc~o-C2.2. Ihepta-2,5-diene 9 (18.2 g, 0.07 mol) was dissolved in tetrahydrofuran (100 cm3) and hydrogenated in the presence of a platinum catalyst on activated carbon (0.1 g) in a Parr apparatus.The hydrogen uptake ceased sharply after the consumption of one equivalent of hydrogen. The reaction mixture was filtered through a bed of Celite and distilled to give 1-(hydroxymethyl)-2,3-bis(trzJEuoromethyl)-7-oxubic~clo2.2.l-hept-2-me 12 (17.5 g, 90), bp 105 "C at 50 mmHg (Found: C, 41.0; H, 2.9; F, 43.4. C,H,F,O, requires C, 41.2, H, 3.0; F, 43.5); v,,,/cm ' 3600-3100, 3000-2800, 1700, 1400-1 100, 900-850 and 700; 6,(250 MHz; CD,COCD,) 1.88 (2 H, m, 5-CH2), 2.13 (2 H, m, 6-CH2), 2.54 (1 H, m, OH), 4.18 (2 H, m, CH,OH) and 5.17 (1 H, m, 4-CH); 6,(235 MHz; CD,COCD,) -59.97 (3 F, s, Z-CCF,) and -60.13 (3 F, s, 3-CCF3); m/z 234 (Mf -28, 100) and 185 (86).Synthesis of 2-(hydroxmethyl)-3,4-bis(trifluoromethyl)furan 14 1-(Hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxabicyclo-C2.2.1Ihept-2-ene 12 (16.0 g, 0.06 mol) was passed dropwise through a glass tube packed with glass wool at 400 "C in a slow current of nitrogen. Volatile material was collected in a trap maintained at -78 "C, and distillation gave 2-(hydroxymethyl)-3,4-bis(trlJuoromethyllfuran 14 (1 3.8 g, 9773, bp 108 "C at 760 mmHg (Found: C, 35.7; H, 1.8; F, 49.2. C,H,F,O, requires C, 35.9; H, 1.7; F, 48.7); vmaX/cm-' 3600- 3000, 2800, 1575, 1400, 1325-1275, 1200, 1100, 900 and 700; 6,(250 MHz; CDC1,) 3.26 (1 H, br, OH), 4.26 (2 H, s, CH,) and 7.40 (1 H, S, CH); 6,(235 MHz; CDC1,) -55.78 (3 F, S, 3-CCF-3) and -58.29 (3 F, s, 4-CCF,); m/z 234 (M', 99) and 135 (100).J. Chem. SOC.,Perkin Trans. 1, 1996 1097 Synthesis of 2,3-bis(trifluoromethyl)benzyl alcohol 16 Tetrahydrofuran (100 cm3) was added to titanium tetrachloride (10 cm3, 0.60 mol) at 0 "C, with stirring, under an atmosphere of dry nitrogen. To this suspension lithium aluminium hydride (0.27 g) and triethylamine (1.6 g, 0.016 mol) were added separately. After heating at reflux for 15 min, the reaction was allowed to cool to room temperature before 1-(hydroxymethy1)- 2,3 -bis( trifluoromethyl)-7-oxabicycloC2.2.I hepta-2,5-diene 9 (2.0 g, 7.7 mmol) was added. Once the addition was completed the reaction was stirred at room temperature for 48 h, then poured into water (40 cm3) and extracted with dichloromethane.The dichloromethane solution was dried (MgSO,) and evaporated, and the desired product was isolated by preparative scale GLC (1 0 SE30, 100 "C), giving 2,3-bis(trlfluoromethyl)-benzyl alcohol 16 (1.2 g, 65) (Found C, 4.5; H, 2.4. C,H6F60 requires C, 44.2; H, 2.45; F, 46.72); v,,,/cm-' 3600-3100, 2900, 1300, 1200-1 100, 800 and 750; 6,(250 MHz; CD,COCD,) 3.69 (1 H, br, OH), 5.71 (2 H, s, CH,) and 8.71- 9.06 (3 H, m, CH); 6,(235 MHz; CD,COCD,) -54.83 (3 F, s, 2-CCF3) and -57.78 (3 F, s, 3-CCF,); m/z 244 (M', 27), 175 (100) and 127 (86). Synthesis of 1,4-bis(hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxabicyclo2.2.lhepta-2,5-diene 10 A mixture of 2,5-bis(hydroxymethyl)furan (12.8 g, 0.1 mol) 1 (16.0 g, 0.1 mol) and tetrahydrofuran (20 g) was heated at 100 "C in a rocking furnace for 24 h.Excess 1 was removed under vacuum (100 mmHg) to leave a colourless liquid (48.4 8). Solvent was removed under reduced pressure to leave an off- white solid, which was recrystallised from MeOH to give l,4-bis(hydroxymethyI)-2,3-bis(trz~uoromethyI)-7-oxabic~clo-2.2.lhepta-2,5-diene 10 (25.1 g, 87), mp 130 "C (Found: C, 41.3; H, 2.75; F, 39.2. CloH8F,03 requires C, 41.3; H, 2.75; F, 39.3); vmax/cm ' 3600-3100, 2900, 1625, 1350- 1050, 875 and 700; 6,(250 MHz; CD,COCD,) 4.1 1 (4 H, s, CH,), 4.42 (2 H, br, OH), 7.21 (2 H, s, CH); 6,(235 MHz; CD,COCD,) -60.97 (s, CF,); m/z 271 (M' -19, 473, 213 (100) and 145 (62).Synthesis of 1,4-bis(hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxabicyclo2.2.1 hept-2-ene 13 1,4-Bis(hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxabicyclo-2.2.1hepta-2,5-diene 10 (20.2 g, 0.07 mol) was dissolved in tetrahydrofuran (100 cm3) and hydrogenated in the presence of a platinum catalyst on activated carbon (0.1 g) in a Parr apparatus. The hydrogen uptake ceased sharply after the consumption of one equivalent of hydrogen. The reaction mixture was filtered through a bed of Celite and evaporation of the solvent gave an off-white solid, which was recrystallised OH); 6,(235 MHz; CD,COCD,) -56.46 (s, CF,); m/z 264 (M', 48) and 247 (100). Synthesis of l-bromo-2,3-bis(trifluoromethyI)-7-oxabicyclo-2.2.lhepta-2,5-diene 11 A mixture of 2-bromofuran (6.4 g, 0.045 mol), hexafiuorobut-2- yne 1 (8.0 g, 0.05 mol) and tetrahydrofuran (14 g) was heated at 140 "C in a rocking furnace for 24 h.Excess 1 was removed under vacuum (100 mmHg) to leave a dark brown liquid (28.4 g) and the desired product was isolated by preparative scale GLC (10 SE30, I10 "C), giving 1-bromo-2,3-bis(trlJluoromethyl)-7-oxabicydo2.2.lhepta-2,5-diene11 (1.5 g, 11) (Found: c, 33.0; H, 1.4; F, 39.4. C8H3BrF60 requires C, 32.9; H, 1.0; F, 39.1); vma,./cmpl 3010, 1700, 1350, 1100, 100-850 and 700; 6,(250 MHz; CDCl,) 5.53 (I H, s, 4-CH) and 7.10-7.16 (2 H, m, 5 and 6-CH); 6,(235 MHz; CDCl,) -61.90 (3 F, s, Z-CCF,) and -62.99 (3 F, s, 3-CCF3); m/z 281 (M+ -26, 100) and 201 (60). Synthesis of isomers of 5-fluoro-5,6-bis(trifluoromethyl)-7-oxa-bicyclo2.2.1 hept-2-ene 17a,b A mixture of furan (4.5 g, 0.066 mol) and 1,1,1,2,4,4,4-heptafluorobut-2-ene 2 (12.0 g, 0.066 mol) was heated in a rocking furnace for 24 h.Excess 2 was removed under vacuum (100 mmHg), and the residual liquid was shown to contain two pairs of diastereoisomers which were isolated by preparative scale GLC (10 SE30, 50 "C). 5-exo-Fluoro-5,6-bis(trifluoromethyl)-7-oxabicyclo2.2.1 -hept-2-ene 17a. (6.8 g, 38) (Found: C, 38.8; H, 2.1 1; F, 52.9. C8H,F,0 requires C, 38.5; H, 2.0; F, 53.2); v,,,/crnp' 3000, 1400, 1300-1125,900, 700 and 675; 6,(250 MHz; CDCl,) 3.17 (1 H, dq, J 12.2 and 9.0, CHCF,), 5.42 (2 H, m, CHO), 6.42 (1 H, m, CHCHO) and 6.74 (1 H, m, CHCHO); 6,(235 MHz; CDC1,) -64.96 (3 F, s, CFCF,), -75.99 (3 F, s, CHCF,) and -182.91 (1 F, s, CF); m/z249 (M' + 1,5),214(51), 181 (23), 145 (50),69 (24) and 68 (100).5-endo-Fluoro-5,6-bis(trifluoromethyl)-7-oxabicyclo2.2.11-hept-2-ene 17b. (6.8 g, 39) (Found: C, 38.7; H, 2.22. C8H,F,0 requires C, 38.5; H, 2.0); v,,,/cm ' 3000, 1400, 1300-1125, 900, 700 and 675; 6,(250 MHz; CDCI,) 3.62 (1 H, dqd, J 12.6, 8.9 and 4.3, CHCF,), 5.40 (2 H, m, CHO), 6.68 (1 H, m, CHCHO) and 6.91 (1 H, m, CHCHO); 6,(235 MHz; CDCl,) -68.81 (3 F, s, CFCF,), -79.23 (3 F, s, CHCF,) and -183.75 (1 F, s, CF); m/z 214 (M+ -34,42), 145 (100) and 69 (1 8). Synthesis of isomers of 5-fluoro-5,6-bis(trifluoromethyl)-bicyclo2.2.1 hept-2-ene 18a,b A mixture of cyclopentadiene (4.35 g, 0.066 mol) and from MeOH to give l,4-bis(hydroxyrnethyl)-2,3-biL~(trz~uoro-1,1, I ,2,4,4,4-heptafluorobut-2-ene2 (1 2.0 g, 0.066 mol) was methyl)-7-0xabicyclo2.2.1Jhept-2-ene 13 (17.3 g, 85), mp 152"C (Found: C, 41.1; H, 3.4; F, 39.5.CloH,,F,03 requires C, 41.0; H, 3.4; F, 39.0); v,,,/cm-' 3500-3200, 2950-2800, 1450, 1400-1050, 900 and 700; 6,(250 MHz; CD,COCD,) 1.52-2.04 (4 H, m, 5 and 6-CH,), 3.99 (4 H, s, CH,OH) and 4.20 (2 H, br, OH); 6,(235 MHz; CD,COCD,) -59.85 (s, CF,); m/z 263 (M+ -19,5473,212 (100) and 149 (33). Synthesis of 2,5-bis(hydroxymethyl)-3,4-bis(trifluoromethyl)-furan 15 1,4-Bis(hydroxymethyl)-2,3-bis(trifluoromethyl)-7-oxabicyclo-C2.2.11hept-2-ene 13 (8.0 g, 0.027 mol) was passed dropwise through a glass tube packed with glass wool at 400 "C in a slow current of nitrogen. Volatile material was collected in a trap maintained at -78 "C, and recrystallisation from MeOH gave 2,5-bis(hydroxymethy~-3,4-bis(trz~uoromet~zyI)furan15 (6.9 g, 96), mp 64deg;C (Found: C, 36.3; H, 2.3; F, 43.2.C8H,F,03 requires C, 36.4; H, 2.3; F, 43.1); v,,,/cm-' 3600-3050, 2950, 1600, 1425, 1350, 1225-1176, 1100, 750 and 700; 6,(250 MHz; CD,COCD,) 4.66 (4 H, s, CH,) and 5.00 (2 H, br, 1098 J. Chem. SOC.,Perkin Trans. 1,1996 heated in a rocking furnace for 24 h. Excess 2 was removed under vacuum (100 mmHg), and the residual liquid (16.1 g) was shown to contain two pairs of diastereozsomers which were isolated by preparative scale GLC (10 SE30, 50 "C).5-exo-Fluoro-5,6-bis(trifluoromethyl)bicyclo2.2.11 hept-2-ene 18a. (5.4 g, 33) (Found: C, 44.0; H, 2.8; F, 53.6. C9H7F7 requires C, 43.6; H, 2.8; F, 53.6); v,,,lcm 2950, 1375, 1250, 1200-1 100,725 and 600400; 6,(250 MHz; CDCl,) 1.37 (2 H, AB,J7.9, CH,), 2.55 (1 H, m, CHCF,), 3.23 (2 H, m, CHCH,), 5.96 (1 H, m, CHCH) and 6.20 (1 H, m, CHCH); 6,(235 MHz; CDCl,) -65.16 (3 F, s, CFCF,), -77.18 (3 F, s, CHCF, and -176.86(I F, s, CF); m/z248 (M+, 2), 109 (10) and 66 (100). 5-endo-Fluoro-5,6-bis(trifluoromethyl)bicyclo2.2.11 hept-2- ene 18b. (5.4 g, 33) (Found: C, 44.0; H, 2.8; F, 53.6. C9H,F, requires C, 43.6; H, 2.8; F, 53.6); vmax/cmpl 2950, 1375, 1250, 1200-1 100, 725 and 600400; 6,(250 MHz; CDCl,) 2.00 (2 H, AB,J7.9, CH,), 2.77 (1 H, m, CHCF,), 3.40 (2 H, m, CHCH,), 6.22 (I H, m, CHCH) and 6.43 (1 H, m, CHCH); 6,(235 MHz; CDCl,) -65.16 (3 F, s, CFCF,) -78.73 (3 F, s, CHCF,) and -180.26 (1 F, s, CF); m/z 248 (M', 279, 109 (9) and 66 (100).Synthesis of 2,3-bis(trifluoromethyl)bicyclo2.2.1 hepta-2,5-diene 20 A mixture of 18a and 18b (3.7 g, 0.015 mol) was added dropwise to a stirred solution of potassium tert-butoxide (3.35 g, 0.035 mol) in tert-butyl alcohol (25 cm3). After heating at reflux for 1 h, the reaction mixture was poured into water (15 cm3). extracted with ether, dried (MgSO,) and evaporated to give a pale yellow liquid (3.8 g). The desired compound was isolated by preparative scale GLC (10 SE30, 100 "C), giving 2,3-bis- (tri~uoromethyl)bicyclo2.2.lhepta-2,5-diene20 (1.9 g, 55) (Found: C, 47.7; H, 2.6; F, 50.5.Calc. for Camp;F,: C, 47.4; H, 2.6; F, 50.0); v,,,/cm 3000, 2925, 1400-1100, 800-700 and 550-475; 6,(250 MHz; CDCI,) 2.29 (2 H, m, CH,), 3.93 (2 H, s, CHCH,) and 6.96 (2 H, s, CHCH); 6,(100 MHz; CDC1,) 53.07 (s, CH,), 74.12 (s, CHCH,), 122.8 (q, J269.4, CF,), 143.0 (s, CHCH) and 149.5 (9, J 17.9, CCF,);S,(235 MHz; CDCl,) -62.04 (s, CF,); m/z 228 (M', 19) and 159 (100) Synthesis of 3,4-bis(trifluoromethyl)furan 3 Fluoroalkene 2 (12.0 g, 65.9 mmol) was transferred, under reduced pressure, into a sealed metal tube which had previously been charged with furan (2.8 g, 41.2 mmol) under a counter current of dry nitrogen. The tube was evacuated, sealed and rocked in a furnace maintained at 300 "C for 3 d.It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmospheric pressure. The residual solution was filtered and distilled to give 3,4-bis(trifluoromethyl)furan3, (5.9 g, 70) bp 87-89 "C (lit.,' 88-89 "C) (Found: C, 35.2; H, 1.1. Calc. for C,H,OF,: C, 35.3; H, 1.0); v,,,,/cm-' 3100, 1550, 1350-1 150, 900, 750, 600 and 400; 6,(250 MHz; CDCl,) 7.85 (s, CH); 6,(100 MHz; CDCl,) 115.8 (q, J 41.0, CCF,), 120.0 (9, J 267.8, CF,)and 140.4 (s, CH); 6,(235 MHz; CDCI,) -59.87 (s, CF,); 204 (M ', 88),185 (100) and 69 (35). Synthesis of 2,5-dimethyl-3,4-bis(trifluoromethyl)furan 21 Fluoroalkene 2 (6.8 g, 37.4 mmol) was transferred, under reduced pressure, into a sealed metal tube which had previously been charged with 2,5-dimethylfuran (2.0 g, 20.8 mmol) under a counter current of dry nitrogen.The tube was evacuated, sealed and heated in a furnace maintained at 200 "C for 2 d. It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmospheric pressure. The residual solution was filtered and distilled to give 2,5-dimethyl-3,4-bis(trifluoromethyl)furan21 (2.96 g, 61), bp 52-56 "C at 12 mmHg (lit.,6 77-78 "C at 88 mmHg); vma,/cm-l 2975-2850, 2350, 1700-1400, 1150 and 1000; 6,(250 MHz; CDCI,) 2.47 (s, CH,);d,(100 MHz; CDC1,) 12.8 (s, CH,), 109.8 (9, J 19.6, CCF,), 123.2 (q, J264.9, CF,) and 152.4 (s, CCH,); 6,(235 MHz; CDCl,) -55.72 (s, CF,);m/z 232 (M', 50), 163 (73), 69 (12) and 43 (100) by comparison with literature data.6 Synthesis of 3,4-bis(trifluoromethyl)-2-furonitrile22 Fluoroalkene 2 (1.2 g, 6.6 mmol) was transferred, under reduced pressure, into a quartz tube which had previously been charged with 2-furonitrile (0.4 g, 4.3 mmol) under a counter current of dry nitrogen.The tube was evacuated, sealed and heated in a furnace maintained at 250 "C for 24 h. It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmospheric pressure. The residual solution was filtered and was shown by GLC-MS to consist of two components in a 7:2 ratio.Distillation of this mixture at 0 "C and 0.I mbar gave 3,4- bis(trifluoromethy1)furan 3 (0.2 g, 21 ), as above. This left a pale brown liquid identified as 3,4-his(mfl~oro- methyl)-2-furonitrile 22 (0.7 g, 71). An analytical sample was isolated by preparative GLC (SE30, 50deg;C) (Found: C, 36.9; H, 0.5; N, 6.3. C,HF,NO requires C, 36.7; H, 0.4; N, 6.1); vmaX/cm-' 2950, 2250, 1750-1 500, 1375-1 100, 800 and 550425; 6,(250 MHz; CDCI,) 7.62 (s, CH); 6,(100 MHz; CDCl,) 115.17(~, CCN), 117.44(q, J39.7, CCF,), 118.24(q, J 40.3, CCF,), 120.49 (9, J269.7, CF,), 121.33 (9, J 269.6, CF,), 121.54 (s, CN) and 146.24 (s, CH); 6,(235 MHz; CDCl,) -59.37 (s, CF,) and -64.32 (s, CF,); mjz 229 (M', 9573, 2I0 (100) and 69 (86). Attempted synthesis of 3,4-bis(trifluoromethyl)-2-furoic acid 26 Fluoroalkene 2 (11.1 g, 61.0 mmol) was transferred, under reduced pressure, into a sealed metal tube which had previously been charged with 2-furoic acid (4.5 g, 40.1 mmol) under a counter current of dry nitrogen. The tube was evacuated, sealed and rocked in a furnace maintained at 300 "C for 24 h.It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmospheric pressure. The residual solution was filtered and distilled to give 3,4-bis(trifluoromethyl)furan3 (3.2 g, 39) as above. Synthesis of methyl 3,4-bis(trifluoromethyl)-2-furoate 23 Fluoroalkene 2 (1.6 g, 8.8 mmol) was transferred, under reduced pressure, into a quartz tube which had previously been charged with methyl 2-furoate (0.8 g, 6.3 mmol) under a counter current of dry nitrogen.The tube was evacuated, sealed and heated in a furnace maintained at 250 "C for 24 h. It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmospheric pressure. The residual solution was filtered and identified as methyl 3,4-bis(trifluoromethyl)-2-furoate23 (1.2 g, 85); v,,,/cm-' 3200, 2950, 1800-1 700, 1500, 1350-1 100, 800 and 550-450; 6,(250 MHz; CDC1,) 3.82 (3 H, s, CH,) and 7.91 (1 H, s, CH); 6,(100 MHz; CDCl,) 52.95 (s, CH,), 117.89 (9, J 41.1, CCF,), 119.01 (4, J39.8, CCF,), 120.55 (9, J270.1, CF,), 121.09(q, J269.8, CF,), 145.43(s, CO,Me), 146.06 (s, CH) and 156.56 (s, CO,); 6,(235 MHz; CDCl,) -55.75 (s, CF,) and -58.40 (s, CF,); m/z 262 (Mf, 25), 231 (100) and 126 (52) by comparison with literature data., Synthesis of ethyl 3,4-bis(trifluoromethyl)-2-furoate24 Fluoroalkene 2 (1.6 g, 8.8 mmol) was transferred, under reduced pressure, into a quartz tube which had previously been charged with ethyl 2-furoate (0.8 g, 5.7 mmol) under a counter current of dry nitrogen.The tube was evacuated, sealed and heated in a furnace maintained at 250 "C for 24 h. It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmospheric pressure. Ether (20 cm3) was added to the residual pale yellow oil, which was then filtered. Rotary evaporation produced a pale yellow oil which was partially crystalline, identified as ethyl 3,4-bis(trifluoromethyl-2-furoate 24 (1.4 g, 89); vmax/cm-' 3000, 1750, 1500, 1350-1300, 1250-1050, 1000 and 500;6,(250 MHz; CDCl,) 1.00 (3 H, t, J7.0, CH,), 3.97 (2 H, q, J7.0, CH,) and 8.18 (I H, s, CH); 6,(100 MHz; CDC1,) 17.38 (s, a,),66.11 (s, CH,), 118.19 (q, J 41.2, CCF,), 119.21 (q, J 42.0, CCF,), 120.23 (9, J 269.5, CF,), 121.01 (q, J 270.2, CF,), 145.89(s, CH), 146.06(s, CC0,Et) and 157.90 (s, CO,); 6,(235 MHz; CDCl,) -59.37 (s, CF,) and -64.32 (s, CF,); m/z 276 (M', 473,248 (46) and 231 (100) by comparison with literature data.Synthesis of 3,4-bis(trifluoromethyl)furan-2-carbaldehyde 25 Fluoroalkene 2 (1.5 g, 8.2 mmol) was transferred, under reduced pressure, into a quartz tube which had previously been charged with furan-2-carbaldehyde (0.5 g, 5.2 mmol) under a counter current of dry nitrogen.The tube was evacuated, sealed and heated in a furnace maintained at 225 "C for 24 h. It was then cooled to liquid air temperature, opened and unreacted 2 was removed by distillation at room temperature and atmos- pheric pressure. The residue was filtered and was shown by GLC-MS and NMR to contain a mixture of unreacted starting aldehyde (43) and 3,4-bis(trifluoromethyl)furan-2-J. Chem. SOC.,Perkin Trans. 1,1996 1099 carbaldehyde 25 (51); SH(250 MHz; CDCl,) 8.07 (1 H, s, CH) and 9.88 (1 H, s, CH0);6,(100 MHz; CDCI,) 118.47 (9,J40.1, CCF,), 119.62 (9, J 40.0, CCF,), 120.42 (9, J 269.5, CF,), 121.68 (9, J 270.1, CF,), 148.75 (s, CH), 151.66 (s, CCHO) and 178.45 (s, CHO); 6,(235 MHz; CDC1,) -55.82 (s, CF,) and -58.29 (s, CF,); mi-?232 (M', 100) and 213 (30) by comparison with literature data., Preparation of 3,4-bis(trifluoromethyl)-2-furoic acid 26 Methyl 3,4-bis(trifluoromethyl)-2-furoate 23 (0.8 g, 3.05 mmol) was added to a round-bottomed flask which had previously been charged with potassium tert-butoxide (2.7 g, 24.1 mmol), water (0.2 g, 11.I mmol) and acetonitrile (10 cm3).The reaction was stirred vigorously for 16 h, and then water (20 cm3) was added and the solution was acidified to pH 1 using H,SO,.Ether (30 cm3) was added, and the ethereal layer was separated and evaporated to produce a yellow oil.This oil was dissolved in petrolkhloroform (4 : l), filtered and slowly evaporated to give pale yellow needles identified as 3,4-bis(trifluoromethyl)-2-furoic acid 26 (0.6 g, 79) mp 123-124 "C, 124-127 "C) (Found: C, 33.9; H, 0.90. Calc. for C,H,F,O,: C, 33.87; H, 0.81); v,,,/cm-' 3600-2800, 2350, 2200, 1750-1 675, 1550, 1300, 1200-1 100 and 1000; 6,(250 MHz; CDCl,) 7.75 (s, CH); 6,(300 MHz; CDCl,) 118.27 (9, J 40.1, CCF,), 119.41 (9, J 40.2, CCF,), 120.29 (q, J270.2, CF,), 121.21(9,J269.6, CF,), 146.80(s CCO,H), 147.29 (s, CH)and 173.27 (s, C0,H); camp;(235 MHz; CDCI,) -58.27 (s, CF,) and -60.14 (s, CF,); m/z 248 (M', 28), 231 (42), 112 (75) and 95 (100). Acknowledgements We thank the Engineering and Physical Sciences Research Council (EPSRC) and TCI for financial support (to A. J. R. and M. H. R., respectively). We also thank Dr P. Odello for helpful discussions, and assistance with the syntheses of compounds 17a,b and 18a,b. References 1 C. D. Weis, J. Org. Chem., 1962, 27, 3693. 2 H. N. C. Wong, Synthesis, 1984, 787. 3 A. B. Abubakar, B. L. Booth and A. E. Tipping, J. Fluorine Chem., 1991,55, 189. 4 A. B. Abubakar, B. L. Booth, N. N. E. Suliman and A. E. Tipping, J. Fluorine Chem., 1992,56, 359. 5 M. Nishida, Y. Hayakawa, M. Matsui, K. Shibata and H. Muramatsu, J. Heterocycl. Chem., 1991, 28,225. 6 M. Nishida, Y. Hayakawa, M. Matsui, K. Shibata and H. Muramatsu, J. Heterocycl. Chem., 1992, 29, 113. 7 A. L. Henne and W. G. Finnegan, J. Am. Chem. Soc., 1949,71,298. 8 J. T. Maynard, J. Org. Chem., 1963, 28, 112. 9 R. D. Chambers and A. J. Roche, J. Fluorine Chem., accepted for publication. 10 R. M. Silverstein, G. C. Bassler and T. C. Morrill, Spectrometric Identification of Organic Compounds, Wiley, New York, 1981. 1 1 W. R. Hasek, W. C. Smith and V. A. Engel, J. Am. Chem. Soc., 1960, 82, 543. Paper 5/08381H Received 28th December 1995 Accepted 22nd January 1996 1100 J. Chem. SOC.,Perkin Trans. I, 1996
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