Rearrangement reactions of bicyclic systems. Part IV. Acid-catalysed rearrangements of 5,6,7,8-tetrafluoro-1,4-dihydro-1-methoxy-3,9-dimethyl-1,4-ethenonaphthalene (1-methoxy-3,5-dimethyltetrafluorobenzobarrelene)

摘要

1974 2711Rearrangement Reactions of Bicyclic Systems. Part 1V.l Acid-catalysedRearrangements of 5,6,7,8-Tetraf luoro-I ,4-dihydro-1 -methoxy-3,9-d imet hyl-l,4-ethenonapht halene (1 - Methoxy-3,5-dimet hyltetraf luoro-benzo barrelene)By Harry Heaney and Steven V. Ley, Department of Chemistry, The University of Technology, Loughborough,The rearrangement of the title compound in trifluoroacetic acid was shown to be directed by the methyl groups,giving 5,6,7,8-tetrafluoro-3.4-dihydro-4,1 O-dimethyl-l,4-ethenonaphthalen-2(1 /-/)-one (5). On the other handthe title compound gave the lactone 7.8.9.1 O-tetrafluoro-I ,2,5,6-tetrahydro-2,6-dimethyl-2,6-methano-3-benz-oxocin-4-one (4) in 98 sulphuric acid, and in 70 sulphuric acid 5,6,7,8-tetrafluoro-3-methyl-l -naphthylacetone( 6 ) was an important product.The mechanisms operating have been studied by using deuteriated acids; theresults establish that none of the protonation steps occurs stereospecifically.Leicestershire LEI 1 3TUIN the preceding paper we discussed the acid-catalysedrearrangements of l-methoxytetrafluorobenzobarrelene(1) (5,6,7,8- t etrafluoro- 1,4-dihydro- 1 -met hoxy- 1,4-ethenonaphthalene). The three major ketonic productswere shown to be produced in a non-equilibrating system.On the other hand other workers have shown2 that thehexamethylbenzobarrelenone (2) rearranges in acidicpaper.Part 111, N. J. Hales, H. Heaney, and S. V. Ley, precedingH. Hart and G. M. Love, Tetrahedron Letters, 1971, 2267.media to afford an equilibrium mixture of four ketones.We now report a study of the acid-catalysed rearrange-ment reactions of 5,6,7,8-tet rafluoro- 1 ,kdih ydro- 1 -methoxy-3,9-dimethyl-1,4-ethenonaphthalene (3), pre-pared by the reaction of tetrafluorobenzyne with 3,5-dimethylani~ole.~P.C. Buxton, N. J. Hales, B. Hankinson, H. Heaney, S. V.Ley, and R. P. Sharma, J.C.S. Perkin I , 1974, 2681.4 Preliminary communication, H. Heaney and S. V. Ley,Chem. Comm., 1971, 13422712We hoped that when we subjected compound (3) toacid-catalysed rearrangements, the initial protonationwould be directed by the presence of the methyl groupsto give initially a cation at C-3. When compound (3) wasdissolved in sulphuric acid (98) and then immediatelyadded to an excess of ice, a quantitative yield of a singleproduct, C1,H,,F,O,, was obtained.The i.r. carbonylstretching band was observed at 1730 cm-l and theabsorptions due to methylene groups were not resolvedin the 60 NIHz lH n.m.r. spectrum. This product waseventually identified, by chemical and spectroscopicmethods (see later), as the lactone (4).In an attempt to isolate intermediates we carried outreactions of compound (3)Heating under reflux inlactone (4) (96y0) andMe( 3 )Meunder less vigorous conditions.trifluoroacetic acid gave thethe ethenonaphthalenone (5)( 2 I( 4 )(82). The lactone (4) was obtained in 94 yield whenthe ketone (5) was dissolved in 98 sulphuric acid andimmediately quenched with ice. The rearrangement ofcompound (3) was also studied at 0” in 70 sulphuricacid in the hope that the cations produced might betrapped. Three products were isolated from this reac-tion: the ketone (5) (lay0), the lactone (4) (39y0), andthe naphthylacetone (6) (40).Neither of compounds(4) and (5) was converted into the ketone (6) under thereaction conditions.its the minor product from the reaction of tetrduoro-benzyne with 3,5-dimethylanisole. The structure of theketone (6) was evident from its spectral data (see Experi-mental section).Having established that the ketone (5) could be con-verted into the compound (4), we carried out variouschemical transformations on the latter. Reduction withlithium aluminium hydride gave a diol (7) which wasCompound (5) was already knownJ.C.S.Perkin Iconverted back into the lactone (4) on oxidation withJones reagent. The lactone (4) was hydrolysed by baseto the hydroxy-acid (8), which gave back the lactone onwarming in solution in chloroform (Scheme 1).FJ F F MeIMe( 7 )Me I-( 8 1SCHEME 1 Reagents: i, LiAlH,; ii, Cr0,-H,SO,; iii, NaOH;iv, warm in CHCl,Ring opening reactions of tetrafluorobenzobarrelenoneby means of base have been studied previously.5 Wecarried out reactions of the ketone (5) with aqueoussodium hydroxide in tetrahydrofuran. At room tem-perature we obtained the acid (9), characterised as itsmethyl ester (10). On the other hand the acid (ll),characterised as its methyl ester (12), was obtained froma similar reaction carried out under reflux.Both theacids (9) and (11) were readily cyclised to the lactone (4)( 5 ) ( 9 ) R = H(10) R = MeF/F‘ F ’ Me F Me(11) R=H’ ( 4 )(12) R = MeSCHEME 2 Reagents : i, aq. NaOH-THF at room temp. ; ii, aq.NaOH-THF at reflux; iii, (9) or (11) in 98 sulphuric acidin the presence of sulphuric acid (98). These reactionsare summarised in Scheme 2.1970, 6, 2336.5 I. F. Mikailova and V. A. Barkhash, J . Org. Chem. (U.S.S.R.)1974Although the signals due to the methylene groups inthe lactone (4) were not resolved in the 60 MHz lH n.m.r.spectrum, they did appear as three well resolved ABquartets in the 220 MHz spectrum. The resonances dueto the protons A were observed at T 6.72 and 7.19 (111 ca.18 Hz), those due to the protons B at 7.07 and 7.52 ( I J ca.18 Hz), and those due to the protons C at 7.85 and8.07 (111 ca. 16 Hz, further split by long-range lH,lSFcoupling).F w HF /MeF(131F F F MeF ‘0(15)The ease with which the hydroxy-acid (8) and theolefinic acids (9) and (11) cyclise to the lactone (4) wasfound to be paralleled by reactions of the diol (7) and ofMeH’ ( 5 )H2713the hydroxy-olefin (13) obtained by reduction of the acid(1 1) with lithium aluminium hydride. Thus compounds(7) and (13) gave the cyclic ether (14) in phosphoric acid.In order to establish that the second double bond in theketone (5) was necessary for fragmentation and re-cyclisation to occur, we reduced the benzobarrelenone (5)to the ketones (15) and treated the products with 98sulphuric acid ; they were recovered unchanged.The foregoing data suggest that the lactone (4) and theketone (6) are formed by the mechanism shown inScheme 3.The protonation steps have been followed bythe use of deuteriated acids. A number of the steps inScheme 3 are shown as being concerted, but they may, infact, not be so. Thus for example the fragmentation ofthe ion (16) may not occur as a result of attack at thecarbonyl carbon atom by a nucleophile. In the stronglyacidic medium, fragmentation to an acylium ion is per-haps more likely.Rearrangement of compound (3) in deuteriosulphuricacid followed by quenching with deuterium oxide gavethe lactone (4) which was predominantly trideuteria ted(17). Rearrangement of the compound (3) in trifluoro-acetic 2Hacid gave the 2Hbenz~barrelen~ne (18), whichon further reaction in sulphuric acid gave the 2Hlactone(19).Rearrangement of compound (5) in deuterio-sulphuric acid gave the 2H,lactone (20).The deuteriation levels in the products were determinedby mass spectrometry. However, the values obtainedwere not of high accuracy because of the low abundanceof the molecular ions. The analysis was also complicatedby the incorporation of deuterium into the 2-methylgroup in the lactone (4), presumably via the ion (16).The 220 MHz lH n.m.r. spectra of the lactones (17), (19),and (20) revealed that the incorporation of deuterium wasF’Me Me Me FSCHEME 2714 J.C.S. Perkin Inot stereospecific at any of the three positions.Thus,for example, broadened singlets were observed for each ofthe six possible methylene protons in the lactone (17).The rearrangement of compound (3) in deuteriosulphric2 0 D DF' FMeF' Me I='F FD0( 2 1 1acid-deuterium oxide (7 : 3) gave the ketone (21). Theincorporation of deuterium into the methylene group wasalso complicated by incorporation at other positions(Table), which could have occurred in the ion (22) or thealcohol (23).1H N.m.r. integration values for compound (21)Protons : A B C D ERelative integral {$:; i:: O." 2*9 '*' 1.0 3.0 1.0EXPERIMENTALGeneral methods used are given in ref. 6.Rearvangements of 5,6,7,8-TetrafEuoro- 1,4-dihydro- l-meth-oxy-3,9-dimethyl- 1,4-ethenonaphthalene ( 3 ) .-(i) In 98sulphuric acid.Compound ( 3 ) (2.0 g) was dissolved in98 sulphuric acid (25 ml) at room temperature and wasimmediately added to crushed ice ( 150 g) . The precipitatewas washed with water until the washings were no longeracidic , and then dried to leave 7,8,9,10-tetrafEuoro- 1,2,5,6-tetrahydro- 2,6-dimethyl-2,6-methano-3-benzoxocin-4-one ( 4 )(2.02 g, 1OOyo), m.p. 170-171° (from ethanol) (Found: C,58.2; H , 4.2; F , 26.4; M f , 288. C,,H,,F,O, requiresC, 58.35; H , 4.2; F , 26.35; M , 288), 7 (CDCl,; 60 MHz)6.6-8.4 (6H, m), 8.38 (3H, s), and 8.4 (3H, d, I JIH,F 1-5 H z ) ,vmx, 1730 cm-l; Lx. (EtOH) 262 nm ( E 660).Compound ( 3 ) (200 mg)was added to 70 sulphuric acid (10 ml) at Oo and stirred a tthat temperature for 3 h before pouring onto crushed ice(20 g ) .The mixture was extracted with ether ( 3 x 10 ml)and the combined extracts were washed with water, dried,and evaporated to leave an oil which was separated by(11) In aqueous sulphuric acid.preparative layer chromatography to give, in order ofdecreasing R p value, (i) starting material ( 3 ) (19 mg, lyo);(ii) 5,6,7,8-tetrafluoro-3,4-dihydro-4,10-dimethyl- 1,4-etheno-naphthalene-2( 1H)-one (5) (24 mg, lay0), identical (t.l.c.,g.l.c., and lH n.m.r. spectroscopy) with an authentic sample;(iii) 5,6,7,8-tetrafEuoro-3-methyl- l-naphthylacetone ( 6 ) (69 mg,40), m.p. 104.5" (from hexane) (Found: C, 61.6; H ,3.7; M t , 270-0667. C,,H,,F,O requires C, 62-25; H,3.7; M , 270-0668), T (CDCl,) 2.15-2-35 (lH, m), 2.8-2-9( l H , m), 5.8 (2H, d, IJIH,F 7Hz), 7.5br (3H, s), and 7.7 (3H,s); vmax.(CHCI,) 1725 cm-l (CO), Amx. (EtOH) 275 ( E 5470),281 (6020), and 290 nm (5350) (naphthalene chromophore) ;and (iv) compound (4) (71 mg, 39), identical (m.p. andmixed m.p., t.l.c., and lH n.m.r. spectroscopy) with authen-tic material (above).The ketone ( 6 ) and the lactone ( 4 ) were not converted intoone another in separate experiments carried out under theabove conditions.Compound ( 3 ) (300 mg) in tri-fluoroacetic acid (10 ml) was heated under reflux for 6 h.Removal of the solvent left an oil which was separated bypreparative layer chromatography into the ketone (5) (234mg, 82) and the lactone ( 4 ) (28 mg, 9.5).In a similar experiment a solution of compound ( 3 ) inchloroform was added to a 1 : 1 mixture of 98 sulphuricacid and trifluoroacetic acid at 0'; the usual work-up gavecompounds (5) and ( 4 ) in 87 and 12 yields, respectively.Rearrangement of the Ethenonaphthalenone ( 5 ) in 98Sulphuric Acid.-The ketone ( 5 ) was dissolved in 98sulphuric acid a t room temperature.The usual work-upgave the lactone ( 4 ) (94y0), identical (t.l.c., and i.r. and lHn.m.r. spectroscopy) with an authentic sample.Reduction of the Lactone ( 4 ) with Lithium AluminiumHydride.-The lactone (4) (500 mg) was reduced, in etherealsolution, with an excess of lithium aluminium hydride. Theusual work-up gave 2- (5,6,7,8-tetra$uoro- 1,2,3,4-tetrahydro-3-hydroxy-l,3-dimethyl-l-naphthyl)ethanol(7) (490 mg, 97y0),m.p.105-106" (from ethanol) (Found: C, 57.5; H , 5.55y0 ;M?, 292. Cl,Hl,F,O, requires C, 57.55; H, 5.5; M ,292), 7 (CDC1,) 5.7-6.1 (2H, m, exchangeable), 6.1-6.5(2H, m), 6-8-8.9 (6H, m), 8.6 (3H, d, IJIH,F 2.5 H z ) , and8.65 (3H, s), v,,,. (CHC1,) 3350 cm-l.Oxidation of the Diol ( 7 ) with Jones Reagent.-A solutionof chromium trioxide in sulphuric acid (Jones reagent) wasadded dropwise to a solution of the diol ( 7 ) (100 mg) inacetone (10 ml) until the yellow colour persisted for 5 min.Water (20 ml) was then added and conventional work-upgave the lactone ( 4 ) (100 mg, loo), identical (m.p. andmixed m.p., t.l.c., and i.r. and lH n.m.r. spectroscopy) withan authentic sample (above).Hydrogenation of the Ketone ( 5 ) and Attempted Rearrange-ment of the Ketones (15).-A solution of the ketone (5) inethanol was hydrogenated over palladium-carbon to givethe 5,6,7,8-tetrafluoro-3,4-dihydro-4,10-dimethyl- 1,4-ethanonaphthalen-2( 1H)-ones (15) (99yo), T (CDCl,) 6.1-6.3( l H , m), 7-6-8.9 (5H, m), 8.35 (3H, d, IJIH,F 6 Hz), 8-85( l H , m, IJI 7 H z ) , and 9.18 (2H, d, I J I 7 Hz).The ketones (15) (100 mg) were dissolved in 98 sulphuricacid (2 ml) at room temperature ; work-up in the usual wayafter 1 h gave starting material (99yo), as shown by t.1.c.andlH n.m.r. spectroscopy.Hydrolysis ofthe Lactone (4).-The lactone ( 4 ) (586 mg) inethanol (10 ml) and aqueous sodium hydroxide (15 ml) was6 J. P. N. Brewer, H. Heaney, S. V. Ley, and T. J. Ward,J.C.S.Perkin I , 1974,2688.(iii) I n tricluovoacetic acid1974 2715heated under reflux for 10 min. The cold mixture was addedto water and hydrochloric acid was added (to pH 2). Ex-traction with ether gave 5,6,7,8-tetrafluoro-l,2,3,4-tetra-hydro-3-hydroxy-l,3-dimethyl- l-naphthylacetic acid (8)(310 mg, 50y0), m.p. 126-127O (from chloroform), vmx.3350br and 1722 cm-l; M t 306. The acid (8) was readilyconverted into the lactone (4) by heating a solution inchloroform for Q h. In the solid state the acid (8) wasslowly (1 week) converted into the lactone (4). Elementalanalysis was thus uninformative.Preparation of Methyl 5,6,7,8-Tetra~uoro-1,4-dihydro-1,3-dimethyl-l-naphthylacetate (10) .-The ketone ( 5 ) (100 mg)was dissolved in tetrahydrofuran (0.4 ml) and aqueoussodium hydroxide (1.75 ml; 2 ~ ) and stirred at room tem-perature for 39 h.Water (3 ml) was then added and themixture was extracted with ether. The aqueous phase wasneutralised with hydrochloric acid (pH 2) and extracted withether (3 x 3 ml). The combined extracts were washedwith water, dried, and evaporated to leave 5,6,7, tetra-fluoro- 1,4-dihydro- 1,3-dimethyl- l-naphthylacetic acid (9)(107 mg, looyo), an oil, z (CDCl,) 0.7-1.2br (lH, s), 4.6-4.8 (lH, m), 6-7-69 (2H, m), 6-95 (lH, d, I J I 14.5 Hz), 7.45(lH, d, I J 14.5 Hz), 8-2 (3H, s), and 8.56 (3H, d, IJIH,F 1.5Hz), vmX. 3400-2600br and 1720 cm-l.Treatment of the acid (9) in ethereal solution, with anexcess of ethereal diazomethane gave the methyl ester (10)(lOOO;,) (Found: Mf, 302.0900.Cl,H14F,02 requires M ,302-0930), T (CDC1,) 4.G4.8 (lH, m), 6.5 (3H, s ) , 6.7-6.9(2H, m), 6.92 (lH, d, I J I 15 Hz), 7.45 (lH, d, I J I 15 Hz), 8-15(3H, s ) , and 8.56 (3H, d, J I H , ~ 1.5 Hz); vmx. 1745 cm-l.Preparation of Methyl 5,6,7,8-TetraJuoro- 1,2-dihydro- 1,3-dimethyl- 1-naphthylacetate.-The ketone ( 5 ) (500 mg) washeated under reflux in tetrahydrofuran ( 5 ml) and aqueoussodium hydroxide (15 ml; 2 ~ ) during 18 h. Work-up as inthe previous experiment gave 5,6,7,8-tetrafluoro- 1,2-di-liydro-l,3-dimethyl-l-naphthylacetic acid (1 1) (450 mg,84:/,), *; (CDCl,) -0.4 to -0-15br (lH, s ) , 3-5-3-7 (lH, m),G*8-7-8 (4H, m), 8.05 (3H, s), and 8.52 (3H, d, IJIH,p 3 Hz),v,,,. 3500-2500br and 1720 cm-l.The acid (11) was methylated with an excess of diazo-methane as above to give the methyl ester (12) (Found: M t ,302-0939. C~,,H,,F,O, requires M , 302.0930), T (CDCl,)3.5-3.7 (lH, m), 6.4 (3H, s), 7.0-7-85 (4H, m), 8-08br (3H,s), and 8.59 (3H, d, JJIH.F 3 Hz), vmx 1745 cm-l.Cyclisation of the Acid (9).-The acid (9) (100 mg) wasdissolved in 98 sulphuric acid (5 ml), and after 5 min thesolution was poured onto ice (10 g). The usual work-upgave the lactone (4) (96 mg, loo), identical (t.1.c.andi.r. and lH n.1n.r. spectroscopy) with an authentic sample.Cyclisation of the Acid (1 1).-The acid (1 1) (130 mg) wasclissolved in 9876 sulphuric acid (2 ml), and after 5 min thesolution was poured onto ice (15 8). The usual work-upgave the lactone (4) (125 mg, 96), identical (t.1.c.and i.r.and lH n.m.r. spectroscopy) with an authentic sample.Reduction of the Acid (13) with Lithium AluminiumHydride and Cyclisation to the Ether (14) .-The acid ( 13) ( 1 g)was reduced with an excess of lithium aluminium hydride inether and gave, after the usual work-up, 2-(5,6,7,8-tetra-fluoro- 1, 2-dihydro- 1, S-dimethyl- l-naphthy1)ethanol ( 13)(804 mg, 85), z (CDC1,) 345-3.75 (lH, m), 6.4 (2H, t, J I7 Hz), 6-6-6.9br (lH, s, exchangeable), 7-7-8.3 (4H, m),8-15br (3H, s ) , and 8-68 (3H, d, IJI,,p 4 Hz).The alcohol (13) (300 mg) was shaken at room temperaturefor 4 days in orthophosphoric acid (6 ml; 887;) and thenpoured into water (50 ml). Extraction with ether ( 5 x 10ml) and the usual work-up gave 7,8,9,1O-tetrafluoro- 1,2,5,6-tetrahydro-2,6-dimethyl-2,6-methano-4H-3-benzoxocin (14)(270 mg, 90) (Found: C, 61.45; H, 5.1; M t , 274.Cl,H14F40 requires C, 61.3; H, 5.15 ; M , 274), T (CDCl,)6.05-7.0 (3H, m), 7-1-7-3 (2H, m), 8-1-8-8 (4H, m), 8.5(3H, d, 1IIH.F 5.5 Hz), and 8-77 (3H, s).Cyclisation of the Diol (7).-The diol (7) (100 mg) wasdissolved in orthophosphoric acid (2 g; 88) and heated at100" for 1 h.The cold mixture was added to ice and, afterthe usual work-up and preparative layer chromatography,gave the ether (14) (38 mg, 40), identical (t.1.c. and i.r. andlH n.m.r. spectroscopy) with the compound prepared asabove.Deuteriation Experiments.-Tri@uoroacetic 2Hacid.Addition of deuterium oxide to trifluoroacetic anhydride(over 2 days) followed by distillation gave trifluoroacetic2H acid.Rearrangement reactions with deuteriated acids. Thedeuteriation experiments were carried out as in the experi-ment with non-deuteriated acids and gave compound (18),T (CCl,) 3-75-3.95 (lH, m), 5.4-5-6 (lH, m), and 7.85-8.2(7H, m), mfe 271 (Mf, 2H >99) and 228 (M - 43);compound (17), T (CDC1,; 220 MHz) 6.78br ( s ) , 7.14br ( s ) ,7.22br ( s ) , 7.55br (s), 7.89br (s) and 8.12 br (s); compound(19), 7 (CDCl,; 220 MHz) 6.72 (lH, d, I J 1 ca. 18 Hz), 7-14br(s), 7.19 (lH, d, I J I ca. 18 Hz), 7.55br ( s ) , 7.85 (lH, d, I J I ca.16 Hz), and 8.07 (lH, d, I J I ca. 16 Hz); and compound (20),T (CDC1,; 220 MHz) 6.78br (s), 7.07 (lH, d, I J I ca. 18 Hz),7.22br (s), 7-52 (lH, d, I J 1 ca. 18 Hz), 7-89br (s), and 8-12brWe thank the S.R.C. for a research studentship (toS. V. L.) and for high-field lH n.m.r. spectra and accuratemass measurements (through the P.C.M.U., Harwell). Wealso thank the Imperial Smelting Corporation, hvonmouth,for gifts of bromopentafluorobenzene.4/1241 Received, 24th June, 19741( s )