Reactions involving fluoride ion. Part 36. Aromatic amines as carbon nucleophiles in reactions with unsaturated fluorocarbons

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1994 Reactions Involving Fluoride Ion. Part 36.' Aromatic Amines as Carbon Nucleophiles in Reactions with Unsaturated Fluorocarbons Richard D. Chambers,"## Stewart R. Kornb and Graham Sandford# a Department of Chemistry, University of Durham, South Road, Durham OH7 3LE, UK lC1 Specialities, North of England Works, PO Box A38, Leeds Road, Huddersfield, Yorkshire HD2 IFF, UK N,N-Dimethylaniline and N-methyl indole react as carbon nucleophiles with perfluorocycloal kene derivatives, giving products 6a and 6b arising from allylic displacement. 1,8-Bis(dimethy1amino)-naphthalene 7, reacts through the 4,5-positions as a difunctional nucleophile, giving a novel annelation. Reactions with 2 and 3 are regiospecific leading to products 9 and 8, respectively.Reaction of perfluorobicyclopentylidene 4 with 7 gives first, through defluorination, the diene 19 and then by annelation of this the product 14. The colours of the products are evidence of extensive charge separation. In previous parts of this series of papers involving fluoride ion- induced reactions, we have described syntheses of unusual perfluorocycloalkene derivatives, e.g. These are 1 2 3 4 especially interesting because they each involve four electron- withdrawing groups attached to the double bond, thereby activating the system towards nucleophilic attack. Nevertheless, because there is no group attached to the double bond that can be directly displaced. Consequently, the resultant system 5 is often very susceptible F Nuc 5 to further attack and, therefore, these systems frequently act as difunctional electrophiles.There is a vast literature concerning processes which involve nucleophilic attack on perfluoroal- kenes but there is limited information concerning reactions of tertiary aromatic amines with these systems. Such amines are, of course, extremely reactive towards electrophilic aromatic substitution but, surprisingly, there have not been any reported examples, to our knowledge, of perfluorinated alkenes acting as electrophiles in reactions with these systems. However, we have now discovered some examples of nucleophilic attack on fluorinated alkenes by aromatic amines reacting through carbon of the aromatic ring. For example, N,N-dimethylaniline reacted with perfluorobicyclobutylidene 1 to give 6a by nucleophilic attack, accompanied by allylic displacement of fluoride ion; N-methylindole reacted in an analogous way to give 6b.We have also found that 1,8-bis(dimethylarnino)naphthal-ene' 7reacts as a difunctional nucleophile with some of these systems leading to a novel annelation. Reaction with 3, gave product 8 through electrophilic attack at the 4-and 5-positions in the I ,8-bis(dimethy1amino)naphthalene and, similarly, reaction of 7 with 2 gave the analogous product 9 (Scheme 1). At first sight it is surprising that these annelations are regiospecific. 6 NMe2 I 1+ i * 6b X - d bsol; Me Me Me2N NMe2 +3 ~ 7 8 Me,N NMe,It 7+2 A 9 Reagents and conditions: i, MeCN, reflux, overnight However, in each case, this specificity can be rationalised on the basis of the initial nucleophilic attack on the perfluoro-cycloalkene derivative 2 or 3.For example, reaction with 2 could take two different initial courses giving 10 or 11 as intermediates. Obviously, the product 9 derives entirely from 11 rather than 10 and this specificity is understandable on the basis of the stability of the developing carbanions 10 and 11. The carbanion 11 would be the more stable since the charge develops on a carbon atom contained in the more strained ring: this happens because the carbon of the four-membered ring must have more s-character in the orbital containing the developing charge.Structures of 8 amd 9 were derived from NMR data. First, 72 J. CHEM. SOC. PERKIN TRANS. I 1994 Me,+ ,Me Me2N (NMe2 Me2N@-t 9 Scheme 1 + Nuc-mor@@ 11 Nuc=7 NUC= 71 Me2N NMe2 Me2N NMe2 9II II 13 12 the pattern of the proton chemical shifts etc., were entirely consistent with a variety of data for other 4,5-disubstituted derivatives of 1,8-bis(dimethylamino)naphthaIene 7.* The 9F NMR data for 8, clearly indicated trifluoromethyl groups attached to a saturated site, and two difluoromethylene groups, consistent with the unsaturated four-membered ring in 8. Obviously, these data are quite inconsistent with structure 13 which would be obtained by alternative regiochemistry of nucleophilic attack on 3. Similar arguments led to the structure 9; the 19F NMR spectrum showed four resonances in the difluoromethylene region, with shifts in the cyclobutene ring similar to those observed in 8.In contrast, structure 12, which would arise from alternative regiochemistry, would be expected to show five distinguishable resonances in the difluoro-methylene region. Reaction of 1,8-bis(dimethylarnino)naphthalene 7 with per- fluorobicyclopentylidene 4 was more complex. In concentrated solutions in acetonitrile, a dark green solid was obtained, which was sparingly soluble but could be recrystallised from aceto- nitrile. However, no NMR signals could be obtained, suggesting a paramagnetic system, reminiscent of the classical Wurster salts.' However, it was shown by elemental analysis and mass spectrometry to be a product which had lost two fluorine atoms from the starting material 4 as well as further reaction with 7.A possible structure is 14. Nevertheless, in high dilution in acetonitrile, some products were obtained that could be characterised. As before, the product was a dark solid but chromatography over alumina gave three fractions: (a) a solid identical (MS, IR, m.p.) with the above 14; (b) yellow-green crystals with a metallic lustre 15 which gave a dark purple solution; (c) a bright purple solid 16, that gave a green solution! The fraction (b) was identified as the ketone 15 by NMR spectroscopy. In particular, a 2-D "F COSY spectrum confirmed difluoromethylene groups in a saturated cyclo- pentane ring, i.e.shifts similar to product 9, as well as di- fluoromethylene groups in the unsaturated ring. The structure 14 15 16 15 is advanced, over the other possible positions of carbonyl because only in this structure do we obtain maximum charge separation, which would account for the remarkable colour changes with phase. The acetonitrile used was anhydrous and therefore hydrolysis must occur during chromatography. Fraction (c), was also shown to be a hydrolysis product apparently derived from 14. The structure 16 again was derived from NMR data and, particularly, a 2-D 19FCOSY experi- ment, from which we could deduce (i) the presence of five difluoromethylene groups, (ii) the shifts derived from di- fluoromethylene groups in the cyclopentenone ring showed close similarity to those in 15, and (iii) the remaining three difluoromethylene groups are consistent with those in a variety of similar perfluorocyclopentene derived ~ysterns.~'~ The most reasonable mechanism for formation of these unusual systems is contained in Scheme 2, where the opportunities for significant charge separation suggests the basis of the remarkable colour changes that occur. The opportunities for charge transfer in the solid state could also account for the metallic appearance.It is curious, that system 2 reacts by an initial two-electron transfer, i.e. nucleophilic attack, whereas 4 obviously undergoes a one-electron transfer, leading to defluorination prior to subsequent nucleophilic attack by 1,8-bis(dirnethylamino)-naphthalene.We have previously shown that defluorination of 4 by sodium amalgam may be achieved lo but initial defluor- ination by 7 is surprising. However, we can envisage a one- electron transfer process leading to 17 (Scheme 3), followed by loss of fluoride ion giving 18 and then the process repeated leading to the diene 19. The latter was not observed but reacted with 7 to give the product 14. In a separate experiment, 7 reacted with the diene 19 to give the same product 14. The most obvious explanation of the different mode of attack of 1 and 4 in reactions with 7 stems from activation by strain in the four- membered ring system. For example, 1 is of greatly enhanced reactivity over 4 in reactions with neutral ethanol" and, consequently, 2 is much more reactive than 4 towards nucleophilic attack.Experimental All materials were either obtained commercially (Aldrich) or prepared by literature procedures. 2-4 All solvents were dried prior to use by literature procedures. NMR spectra were recorded on either a Varian VXR400S or a Bruker AC250 Spectrometer. In "F NMR spectra, upfield shifts are quoted as negative. J Values are given in Hz. Mass spectra were recorded on a Varian VG 7070E spectrometer, IR spectra on a Perkin- Elmer 577 Grating Spectrophotometer and UV spectra on a Perkin-Elmer Lambda 3 spectrophotometer using standard techniques. Elemental analyses were obtained on either a Perkin-Elmer 240 or a Carlo Erba Elemental Analyser.Melting points were recorded at atmospheric pressure and are uncor- rected. Reactions of Perjluorobicyclobutylidene 1.-(a) With N,N-dimethylandine. A mixture containing N,N-dimethylaniline (0.5 g, 4.1 mmol) and perfluorobicyclobutylidene 1(1.1 g, 3.4 mmol) J. CHEM. SOC. PERKIN TRANS. I 1994 "iH 15 Scheme 2 L J L17 ia 'I1P.etc. 14 7. etc.~ 0-0 19 Scheme 3 was stirred at room temperature overnight in acetonitrile (5 cm3). Water (1 5 cm3) was added to the mixture to precipitate the solid product which was filtered off, recrystallised from aqueous ethanol and vacuum sublimed to yield 1-l'-(p- dimethylaminophenyl)per-uorocyclobutylperJEuorocyclobut-1-ene 6a (1.05 g, 73) as white needles; m.p. 84-85 "C (Found: C, 45.0; H, 2.3; N, 3.2 C16HloF,,N requires C, 45.2; H, 2.3; N, 3.3); vmax/cm-' 1715 (M);6,(250 MHz, CD,CN, Me,Si) 2.96 (6 H, s, NMe,), 6.76 and 7.16 (4 H, AA'XX', JAX 8.7, 3- and 2-ArH); 6,(235 MHz, CD,CN, CFCI,) -101.2 (1 F, s, 2-CF), -114.0 (2 F, S, 4-CF,), -119.0 (2 F, S, 3-CF,), -117.0 and -120.9 (4 F, AB, JAB 214,2'-CF,), -128.0 and -133.9 (2 F, AB, JAB 222,3'-CF,); m/z (EI+) 425 (M+, 100).(b) With N-methylindole. A mixture containing N-methyl- indole (0.4 g, 3 mmol) and perfluorobicyclobutylidene 1 (1.O g, 3 mmol) was refluxed in acetonitrile (5 cm3) overnight. On cooling, the reaction mixture was diluted with water (15 cm3) to precipitate the solid product which was filtered off, dried and purified by vacuum sublimation (oil-bath temp.100 "C, c0.1 mmHg) to give white crystals of 1 -1'-(N-methylindol-3"-yl)per$uorocyclobutylJper-uorocyclobut-1-ene 6b (0.60 g, 46); A,,,(MeCN)/nm 273.6 (log E 3.78), 367.6 (3.45) and 451.2 (3.78); v,,,/cm-' 1680 (M);6,(250 MHz, CD,CN, Me,) 2.81 (6 H, s, 3-NMe2), 2.88 (6 H, s, 4-NMe2), 6.79 and 7.45 (2 H, AX, JAX 8.3,1-H and 2-H), 6.98 and 7.85 (2 H, AX, JAx8.8,5-H and 6-H); 6,(235 MHz, CD,CN, CFCl,) -67.2 (6 F, s, CF,), -105.1 (2 F, S, 9-CF,), -112.5 (2 F, S, 8-CFZ); 6,(100 MHz, CD,CN, Me,) 43.5 (s/br, N-Me), 107.7 (s, C-6a), 108.9 (s, C-2), 11 1.5 (s, C-5), 115-120 (many overlapping peaks, CF, and CF,), 116.7 (s, C-9b), 121.4 (s, C-3a), 123.7 (s, C-9a), 126.0 (s, C-7a), 126.9 (s, C-1), 130.4 (s, C-6), 134.1 (s, C-9c), 152.9 (s, C-3), 153.0 (m, C-7) and 156.1 (s, C-4); m/z (CI+, NH,) 487 (M++ 1, 20). A red solid was also isolated (0.05 g) as yet unidentified; v,,,/cm-' 1790 (GO);6,(235 MHz, CD,CN, CFCl,) -68.9 (s, 6 F) and -110.5(s, 2 F); m/z (EI') 464 (M', 83).(b) With Jluoroalkene 2.A mixture containing 1,8-bis(dimethy1amino)naphthalene 7 (0.6 g, 2.8 mmol) and fluoroalkene 2 (1.0 g, 2.7 mmol) was refluxed overnight in acetonitrile (5 cm3). The solvent was removed to leave an orange solid which was washed with water, collected and dried. The solid was evaporated onto chromatographic alumina from which light petroleum (b.p. 40-60 "C) eluted 3,4-bis(dimethyl- amino)-2',2',3',3',4',4',5',5',8,8,9,9-dodecaJluorospiro8,9-dihy-dro-7H-cyclobutaaphenalene-7-cyclopentane(0.2 g, 13) as orange crystals; m.p.137-1 39 "C;R, 0.5 (Found:C,50.4; H, 3.9; N, 4.4; M+, 548.1 1762. C2,Hl6FI2N2 requires C, 50.3; H, 2.9; N, 5.1; M', 548.1 1219); A,,,(MeCN)/nm 273.6 (log E 4.06), 365.6 (3.74) and 452.8 (4.10); vmax/cm-' 1673 (M);6,(400 MHz, CD,CN, Me,Si) 2.88 (6 H, s, 3-NMe2), 2.94 (6 H, s, 4-NMe,), 6.86 and 7.33 (2 H, AX, JAX 8.4,2-H and 1-H), 7.04and 7.52 (2 H, AX, JAX 8.8, 5-H and 6-H); 6,(376 MHz, CD,CN, CFCl,) -104.9 (2 F, s, 9-CF2), -112.8 and -116.0 (4 F, AB, JAB 249.1,2'-CF,), -114.6 (2 F, S, 8-CF,), -135.2 (4 F, S, m.p. 59-60deg;C (Found: C, 47.25; H, 1.8; N, 3.1. C,,H,F,,N 3'-CF,); 6,(100 requires C, 46.9; H, 1.85; N, 3.2); v,,,/cm-' 1720 (M);6, (400 MHz, CD,CN, Me,Si) 3.85 (3 H, s, N-Me), 7.20 (1 H, t, Jfi,,,6,,7.6,6"-H), 7.33 (I H, t, J5,*,6,,7.6,5"-H), 7.39(1 H, d, J6,,,7,, 8.0, 7"-H), 7.51 (1 H, d, J4,,,5,, 8.3, 4"-H), 7.56 (1 H, S, 2"-H); dF(376 MHz, CD,CN, CFC1,) -100.6 (1 F, S, 2-CF), -114.7 (2F,s,4-CF2), -119.3(2F,s,3-CF2), -117.2and -120.4(4F, AB, JAB 215,2'-CF,), -128.2 and -130.4 (2 F, AB, JAB 221, 3'-CF,); m/z (CI+, NH,) 436 (M' + 1,28).Reactions of 1,8-Bis(dimethylamino)naphthalene7.-(a) With perfluoroisopropylidenecyclobutane3. A mixture containing 1,8- bis(dimethy1amino)naphthalene 7 (0.7 g, 3.2 mmol), the fluoroalkene 3 (1.O g, 3.2 mmol) and acetonitrile (10 cm3) was heated at reflux overnight. Water was added to the mixture to precipitate an orange solid which was filtered off and shown by TLC to contain two components.The solid was evaporated onto chromatographic alumina elution of which with light petroleum afforded 3,4-bis(dimethylamino)-8,8,9,9-tetra~uoro-53-( tri~uoromethyl)-8,9-dihydro-7H-cyclobutaalphenalene8 (1.1 g, 21) as orange crystals; RF 0.5; m.p. 128 "C (from aqueous ethanol) (Found: C, 52.2; H, 3.4; F, 38.0; N, 5.6. C2,H,,F1,N, requires C, 51.9; H, 3.3; F, 39.0; N, 5.8); MHz, CD,CN, Me,Si) 43.0 (s/br, NMe,), 109.4 (s, C-2), 111.4 (s, C-5), 115.4 (s, C-3a), 115-120 (many overlapping peaks, CF,), 128.6 (s, C-1), 134.0 (s, C-9c), 135.8 (s, C-6), 15 1.9 (m, C-7), 154.4 (s, C-3) and 158.2 (s, C-4); m/z(CI', NH,) 549 (M+ + 1,3779. (c) With per-uorobicyclopentylidene 4. (i) At low dilution. A mixture containing 1,8-bis(dimethylarnino)naphthalene7 (1.1 g, 5.1 mmol) and perfluorobicyclopentylidene 4 (1.O g, 2.3 mmol) was stirred overnight at room temperature in acetonitrile (5 cm3) to form a dark olive green precipitate.Water was added to the mixture and the solid was collected by filtration. The solid was adsorbed onto chromatographic alumina from which light petroleum-dichloromethane (4 :1) eluted 3,4-bis(dimethyl- amino)-7,7,8,8,9,9,10,10,11,11,12,12-dodeca~uoro-8,9,11,12-tetrahydro-7H, 1OH-dicyclopenta4,5 :6,7cyclohepta 1,2,3-ij 3-naphthalene 14 (0.54 g, 42); m.p. 24345 "C (decomp.) (from acetonitrile); R, 0.65 (Found: C, 51.3; H, 2.8; F, 40.0; N, 4.9. C2,Hl6F,,N, requires C, 51.4; H, 2.8; F, 40.7; N, 5.0); no NMR data could be recorded; m/z (EI') 560 (M+, 100).(ii) At high dilution. A mixture containing 1,8-bis(dimethyl- amino)naphthalene 7 (0.5 g, 2.5 mmol) and perfluoro-bicyclopentylidene4 (1 .O g, 2.3 mmol) was stirred overnight at room temperature in acetonitrile (1 20 cm3). Evaporation of the mixture under reduced pressure left a solid residue, which was adsorbed onto chromatographic alumina and from which light petroleum-dichloromethane (4 :1) eluted compound 14 (0.23 g, 1873,as above; 3,4-bis(dimethylamino)-2',2',3',3',4',4',5',5',9,9, 10,l O-dodecafluoro- I OH-spiro(cyclopentaalphenylene-7-cyclo-pentan)-8(9H)-one 15 (0.14 g, 10) as bright green metallic- looking flakes; m.p. 280 "C; R, 0.45 (Found: C, 48.4; H, 2.75; N, 4.50. C,4H,,F,,N,0 requires C, 50.0; H, 2.75; N, 4.5.C,,H,,F,,N,O~H,O requires C, 48.5; H, 3.0; N, 4.7); v,,,/cm-' 1720 (M);6,(400 MHz, CD,CN, Me,Si) 2.16 (1 2 H, s, NMe,), 6.95 and 7.25 (2 H, AX, JAX 8.8, 1-H and 2-H), 7.05 and 7.92 (2 H, AX, JAX 8.8, 5-H and 6-H); 6,(376 MHz, CD,CN, CFC1,) -111.0 and -113.4 (4 F, AB, JAB 246.7, 2'- CF,), -117.8 s(pseudo AB), 2F, 10-CF,, -131.4 2 F, s(pseudo AB), 9-CF,, and -132.3 4 F, s(pseudo AB), 3'-CF,; m/z (CI-, NH,) 576 (M+, 72); and 3,4-bis-J. CHEM. SOC. PERKIN TRANS. 1 1994 References 1 R. D. Chambers, M. P. Greenhall and M. J. Seabury, J.Chem. Soc., Perkin Trans. 1, 199 1,206 1. 2 R. D. Chambers, G. Taylor and R. L. Powell, J. Chem. Soc., Perkin Trans. 1, 1980,426. 3 R. D. Chambers, G. Taylor and R. L. Powell, J.Chem. Soc., Perkin Trans. 1, 1980,429. 4 R. D. Chambers, R. S. Matthews, G. Taylor and R. L. Powell, J. Chem. Soc., Perkin Trans. 1, 1980,435. 5 A. E. Bayliff, M. R. BryceandR. D. Chambers, J. Chem. Soc., Perkin Trans. 1, 1987,763. 6 See for example, (a)R. D. Chambers, Fluorine in Organic Chemistry, Wiley-Interscience, New York, 1973, ch. 7; (6) R. D. Chambers and M. R. Bryce in Comprehensive Carbanion Chemistry, vol. 5, eds. E. Buncel and T. Durst, Elsevier, Amsterdam, 1987; (c) R. D. Chambers and R. H. Mobbs, Ado. Fluorine Chem., 1965, 4, 50, and references therein. 7 (a) R. W. Alder, P. S. Bowmann, W. R. S. Steele and (dimethyZamino)-7,7,8,8,9,9,11,11,12,12-decafluoro-8,9,11,12-tetrahydro-7H-dicyclopenta4,5:6,7cyclohepta 1,2,3-01- naphthalen-10-one 16 (0.12 g, 9) as bright purple metallic- looking flakes; m.p. 280 "C; RF0.3 (Found: C, 53.2; H, 3.05; N, 4.75; M', 538.1100900. C,,H,,F,,N,O requires C, 53.5; H, 2.95; N, 5.2; M+, 538.1 10295); v,,,/cm-' 1720 (C=O); 6,(400 MHz, CD,CN, Me,Si) 2.16 (1 2 H, s, NMe,), 6.49 and 6.92 (2 H, AX, JAX 8.8, 5-H and 6-H), 6.51 and 7.33 (2 H, AX, JAX 8.8,2-H and 1-H); 8, (376 MHz, CD,CN, CFC1,) -106.5 and -128.8 (2 F, AB, JAB 278, 12-CF2), -109.3 and -133.1 (2 F, AB, JAB 262, 7-CF2), -119.4 and 128.0 (2 F, AB, JAB 260, 9-CF2), -128.8 and -136.0 (2 F, AB, JAB 283, 11-CF,), -133.4 and -143.3 (2 F, AB, JAB 240, 8-CFz); m/z (EI') 538 (M', 100). D. R. Winterman, J. Chem. Soc., Chem. Commun., 1968, 723; (b) H. A. Staab and T. Saupe, Angew. Chem., Int. Ed. Engl., 1988, 27, 865. 8 N. V. Vistorobskii and A. F. Pozharskii, Z. Org. Chim., 1989, 25, 2154. 9 See for example, J. Hine, Physical Organic Chemistry, McGraw-Hill, New York, 1956, p. 387. 10 M. W. Briscoe, R. D. Chambers, S. J. Mullins, T. Nakamura and F. G. Drakesmith, J,Chem. SOC.,Chem. Commun., 1990, 1127. 11 R. D. Chambers, G. Taylor and R. L. Powell, J. Fluorine Chem., 1980,16, 161. Paper 3/04874H Received 1 1th August 1993 Accepted 20th September 1993