1380 J.C.S. Perkin IReactions of Octaf luoroacridone and Related CompoundsBy David M. Owen, Alan E. Pedler.' and J. Colin Tatlow, Department of Chemistry, The University ofBirmingham, BirminghamA new route to polyfluoroacridones is described and the substitution reactions of octafluoroacridone with methoxideion are discussed, the position of substitution being confirmed by alternative synthesis from an amino-methoxy-octafluorobenzophenone. From octafluoroacridone was prepared 9-chloro-octafluoroacridine, but not nonafluoro-acridine, owing to its ready hydrolysis. Polyfluoroacridones give stable sodium salts, isolable in crystalline form.Ready demethylation of methyl polyfluoroaryl ethers occurred with concentrated sulphuric acid when a carboxy-group or hydrogen atom was para to the methoxy-group; this is explained in terms of protonation of thepara ringcarbon atom.WE recently described the synthesis of octafluoro-acridone by electrochemical oxidation of 2-amino-nonafluorobenzophenone and by pyrolysis of perfluoro-3-phenylanthranil.An alternative synthesis has alsobeen reported.2 We now describe some reactions ofoctafluoroacridone, particularly nucleophilic substitutionby methoxide ion.During this work another method of cyclizing amino-polyfluorobenzophenones to polyfluoroacridones wasdevised. Previous attempts 3*4 to cyclize 2-substitutedpolyfluorobenzophenones by using aqueous potassiumhydroxide and potassium carbonate-dimethylformamidewere only partially successful since the nucleophiliccharacter of the base caused halogenoform-type cleavageof the ketone.However the successful cyclization of2-hydroxy-polyfluorobenzophenones to polyfluoroxan-thones by using potassium fluoride-acetone has beendescribed? although trial experiments with this systemand 2-amino-nonafluorobenzophenone (I) gave onlylow yields of octafluoroacridone (11). We have foundthat good yields (60%) of octafluoroacridone (11) areobtained with anhydrous dimethylformamide and potas-sium fluoride at 100 "C. This reaction was extended togive 1,2,3,4-tetrafluoroacridone (IV) from 2'-amino-2,3,4,5,6-pentafluorobenzophenone (111) and 1,2,4,5,-6,7 ,8-hep t afluoro-3-met hox yacridone (VI) from 2-amino-C. M. Jenkins, A. E. Pedler, and J. C . Tatlow, Tetrahedron,2 S . Hayashi and N.Ishikawa, Chem. Letters, 1972, 2, 99;1971, 27, 2557.Nippon Kagaku Kaishi, 1973, 7 , 1319.octafluoro-4-methoxybenzophenone (V) (see later). The1,2,4,5,6,7,8-heptafluoro-3-methoxyacridone prepared bythis route had the same n.m.r. and i.r. spectra as thecompound previously reported but a higher m.p.SCHEME 1Our original intention was to study the position ofnucleophilic substitution in oct afluoroacridone by pre-paring a monomethoxy-derivative. The position ofsubstitution was then to be confirmed by an unambi-guous synthesis following the route previously emp1oyed.lThe first stage involved the reaction of tetrafluoro-4-methoxybenzaldehyde (VII) with a Grignard reagentprepared from 1 -bromo-2,3,4,5-tetrafluorobenzene, togive the diphenylmethanol (VIII).Oxidation of thiswith chromium trioxide afforded the benzophenone (IX).E. G. Lubenets, T. N. Gerasimova, and E. P. Fokin, Zhur.org. Khim., 1971, 7, 805.P. L. Coe, A. E. Jukes, and J. C . Tatlow, J . Chem. SOC.,1966, 20201975 1381H2no p r o d u c t s & - oca H'MeO\However, attempts to nitrate this ketone with boron diphenylmethanol (VIII). Reduction of the chloridetrifluoride-tetramethylene sulphone-fuming nitric acid over palladium-charcoal gave the diphenylmethane (XI).mixture 5 failed, starting material being recovered in However, attempted nitration of each compoundindifferent yield. In view of the anomalous behaviour (HN0,-H,SO, at 90 "C) failed.OH QIIMe0 o/'D NH,\?"'3. J.0..Me0 /0IICtIt i x L i x $ i(1) " (Xnr) ti (II)SCHEME 2 All unmarked bonds t o fluorine. Reagents: i , 2,3,4,5-tetrafluorophenylmagnesium bromide; ii, CrO,; iii, BF,-HN0,-[CH.J,SO,; iv, conc.H,SO,; v, SOCl,; vi, Pd-H, ; vii, HN0,-H,SO,; viii, KF-DMF; ix, MeO-; x, aq. KOH; xi, POC1,of the octafluoromethoxybenzophenone, the stability of Finally, a suitable amino-methoxy-octafluorobenzo-the compound in concentrated sulphuric acid at 100 "C phenone was obtained by the nucleophilic substitution ofwas investigated. From this reaction no starting 2-amino-nonafluorobenzophenone (I) with methoxidematerial was recovered, the sole product found being ion. A compound was obtained with the appropriate2,3,4,5-tetrafluorobenzoic acid. chemical analysis and i.r.spectrum for a monosubstitutedSince scission of the ketone had occurred, the synthesis derivative. The mass spectrum showed that theof compounds containing an alternative bridging groupobtained in good yield from thionyl chloride and the5 P. L. Coe, A. E. Jukes, and J. C. Tatlow, -1. Chem. SOC. (C),p. L. Coe and A. E. Jukes, Tetrahedron, 1968, 24, was considered. The di??henylmethyl (x) was 1966, 2323;5913J.C.S. Perkin Imethoxy- and amino-groups were in the same poly-fluorophenyl ring, and a comparison of experimental andcalculated chemical shifts for the fluorine n.m.r.spectrum showed the compound to be 2-amino-octa-fluoro-4-methoxybenzophenone (V) .This result is surprising since simple considerationslead to the expectation that substitution by the meth-oxide group would occur in the unsubstituted penta-fluorophenyl ring (because of the deactivating effectof the amino-group).However there is evidencefrom U.V. spectra that in aromatic ketones containinga 2-amino-group there is an appreciable contribution tothe electronic structure of the molecule from resonanceforms of the type (A). Compounds for which this ispossible generally also absorb in the visible region of thespectrum, and 2-amino-nonafluorobenzophenone is yel-low. If, in fact, there is a significant contribution froma resonance form of this type then the anticipatedenhanced reactivity of the unsubstituted ring (beyondthat of hexafluorobenzene) in 2-aminononafluoro-benzophenone towards nucleophiles due to the carbonylfunction will be absent, since delocalization of thenegative charge on the incoming group by the carbonylgroup will no longer be easy.In addition the presenceof the =N+H, group in the substituted ring will renderthat ring more electron-deficient, so increasing itsreactivity towards methoxide. Substitution a t the4-position then means that in the Wheland intermediatethe negative charge is not located on a carbon atombearing fluorine, where I,, repulsion renders the inter-mediate unstable. In addition a canonical form of theintermediate may be written involving a p-quinonoidstructure, regarded as i m p ~ r t a n t . ~ . ~The structure of the 2-amino-octafluoro-methoxy-benzophenone was confirmed by halogenoform-typecleavage with aqueous potassium hydroxide.From theproduct was isolated an amino-methoxy-trifluorobenzoicacid, confirming that the methoxy- and amino-groupswere in the same ring. Since in the proton n.m.r.spectrum the methoxy-signal was a triplet, the acid iseither 2-amino-4-methoxy- (XII) or 2-amino-5-methoxy-trifluorobenzoic acid (XIII). This is consistent with the19F n.m.r. spectrum, and a comparison of calculated6and experimental chemical shifts showed the acid to be(XII). Attempts were made, without success, to preparethe acid by nucleophilic substitution of methyl tetra-fluoro-4-methoxybenzoate, but from reactions withaqueous ammonia or lithium amide only startingmaterial was recovered.6 M. I. Bruce, J . Chem. SOC. ( A ) , 1968, 1459.7 L.Deub and J. M. Vandenbelt, J. Amer. Chem. SOC., 1949,71, 2414.G. M. Brooke, E. J. Forbes, R. D. Richardson, M. Stacey,and J . C. Tatlow, J . Chem. SOC., 1965, 2088; J. Burdon, Tetra-hedron, 1965, 3373 and references therein.The nucleophilic reaction of octafluoroacridone withsodium methoxide in dimethyl sulphoxide-methanolgave a dimethoxy-derivative. The 19F n.m.r. spectrumconsisted of three signals only, indicating that sub-stitution had given a symmetrical derivative. Theproton n.m.r. spectrum consisted of one signal only whichwas a triplet ; the methoxy-group was again couplingwith two adjacent fluorine atoms. A signal due to theacidic proton attached to the nitrogen atom was absentowing to exchange broadening at the high temperaturea t which the proton spectrum was taken.Thus thecompound was either 2,7- or 3,6-dimethoxy-hexafluoro-acridone. The latter structure (XIV) was confirmed bynucleophilic substitution of 3-methoxyheptafluoro-acridone (VI) (obtained from the potassium fluoridecyclization) by methoxide ion, which gave an identicaldimethoxy-derivative.The position of substitution is in general accord withother results of nucleophilic substitution of polyfluoro-nitrogen heterocy~les.~J~ However, under the condi-tions of the reactions described here, in which excess ofsodium methoxide was employed, octafluoroacridonewould be present in the form of the anion. This wouldprobably exist as a resonance hybrid of the two struc-tures (B) and (C), in which (B) is the dominant form, by0- 0analogy with 4-hydroxy-tetrafluoropyridine, where theanion yields on methylation only an 0-methyl product.In considering the most important contributors to theWheland intermediate for nucleophilic substitution influoro-nitrogen heterocycles the favoured resonancestructures are considered to be those where the ringnitrogen atom participates in delocalizing the negativecharge (other structures being unfavourable for thereason outlined above), particularly where 9-quinonoidforms can be drawn.All these factors favour nucleo-philic substitution of octafluoroacridone at the 3-position, for which an important resonance contributorto the stability of the intermediate is (D). This structure0-F ID1OCH, F -is analogous to that postulated as important in thenucleophilic substitution of octafluor~phenazine.~A.G. Hudson, M. L. Jenkins, A. E. Pedler, and J. C . Tatlow,lo R. D. Chambers, M. Hole, W. K. R. Musgrave, R. A. Storey,Tetrahedvon, 1970, 26, 5781.andB. Iddon, J . Chem. SOC. (C), 1966, 2331975Other derivatives of octafluoroacridone were prepared.By reaction with phosphoryl chloride (standard pro-cedure) was obtained 9-chloro-octafluoroacridine (XV) :this was hydrolysed slomly in moist air back to octa-fluoroacridone. Attempted conversion of the chloro-acridine into nonafluoroacridine by potassium fluoride intetramethylene sulphone gave only octafluoroacridone,presumably because of hydrolysis of the product duringthe aqueous work-up.The relatively high acidity of octafluoroacridone andits methoxy-derivatives was demonstrated by theformation of stable sodium salts.Although acridonemay be dissolved in alcoholic potassium hydroxide thesolution of the potassium salt is completely decomposedby water.ll Tri- and tetra-nitro-acridones are con-siderably more acidic and are capable of liberatingcarbon dioxide from aqueous sodium carbonate.llLikewise, substitution of fluorine into the acridonesystem considerably increases the acidity of the NHgroup so that stable sodium salts may be prepared fromoctafluoroacridone (11) and 1,2,4,5,7,8-hexafluoro-3,6-dimethoxyacridone (XIV) . These salts were sufficientlystable to withstand washing, although on prolongedcontact with water slow hydrolysis occurred.The saltswere identified by the absence of OH and NH stretchingfrequencies in the i.r. spectrum and by chemical analysis,although a correct fluorine analysis could not be obtainedowing to interference by sodium.Further experiments were performed to explain thefailure to nitrate successfully 2,2' ,3,3',4' ,5,5', 6-octafluoro-4-methoxybenzophenone (IX) : the behaviour of modelcompounds in the presence of concentrated sulphuricacid was investigated. *ill the compounds studied weretreated with the acid on a steam-bath for 3; h. Asexpected, from pentafluoroanisole and methyl penta-fluorobenzoate only starting material and pentafluoro-benzoic acid, respectively, were recovered. However,from methyl tetrafluoro-4-methoxybenzoate and 2,3,5,6-tetrafluoroanisole, 2,3,5,6-tetrafluorophenol was obtainedin each case.Two mechanisms have been proposed for the demethyl-ation of aromatic ethers by strong acid, the first involv-ing protonation of the oxygen atom of the methoxy-group, the second protonation of the carbon atom parato it, each followed by loss of the alkyl or aryl group fromthe ether.It is unlikely that the difference in stabilityof our anisoles can be ascribed to changes in the proton-ation of the oxygen atom since the inductive propertiesof the pentafluoro- and tetrafluoro-phenyl rings areunlikely to be materially different. However, back-conjugation of electrons from the oxygen atom may wellbe greater in 2,3,5,6-tetrafluoroanisole than in penta-fluoroanisole (due to I , repulsion in the latter case),thus increasing the probability of protonation and hencethe rate of demethylation of the tetrafluoroanisole.11 R.M. Acheson, 'Acridines,' Interscience, New York, 1956.l2 H. Schenkel and M. Rudin-Schenkel, Helv. Chim. Acta, 1948,31, 514; B. R. Brown, W. IT'. Elliott, and D. L. Hammick, J .Chenz. SOC., 1951, 1384; W. bI. Schubert and R. Gardner, J .Anzer. Chenz. SOC., 1953, 75, 1401.The decarboxylation of aromatic acids in acidicmedia has been explained l2 by protonation of the carbonatom bearing the carboxy-group, so that in terms ofthe arguments advanced above the rapid decarboxylationand demethylation of methyl tetrafluoro-4-methoxy-benzoate to 2,3,5,6-tetrafluorophenol may be rational-ized.All these results offer a possible explanation of thedifference towards nitration of 2H-nonafluorobenzo-phenone and the methoxy-derivative (IX).Pre-sumably the presence of the methoxy-group aids proton-ation and cleavage of the phenone to form 2,3,4,5-tetrafluorobenzoic acid and 2,3,5, 6-tetrafluoroanisole,which is itself cleaved and degraded by extended heatingin strong acid.EXPERIMENTALMass spectra were measured on an A.E.I. MS9 spectro-meter; i.r. spectra on a Perkin-Elmer 257 instrument(all solids as Nujol mulls unless otherwise stated) ; and U.V.spectra for ethanolic solutions on a Unicam SP 800 spectro-photometer. N.m.r. spectra were measured with either aPerkin-Elmer R10 or R12B spectrometer a t 38.5 "C unlessotherwise stated.Proton chemical shifts (at 60 MHz) arequoted in 6 values (Me,Si internal standard) and 19Fchemical shifts (at 56.4 MHz) in # values (trichlorofluoro-methane internal standard) except where stated otherwise.Octufluoroacridinone (11) .-To a solution of 2-aminono-nafluorobenzophenone (I) (1.68 g) in dry dimethylforma-mide (DMF) (15 cm3) was added dried potassium fluoride(1.0 g) and the mixture was heated for 5 h at 100 "C. Thesolution was then poured into water (150 cm3), and theyellow precipitate (1.15 g) filtered off and sublimed (200" ;0.02 mmHg) to give octafluoroacridone (11) (1.0 g), m.p.282" (lit.,l 282-284O), with correct i.r. spectrum; #[(CD,),SO; 100 "C; CF3*C0,H internal standard] 67.5J 22 and 8 Hz, F-3), 78.0 (lF, ddd, J 2 , 4 2.6, J3,, 22 Hz,F-4), and 90.5 (lF, dt, J 2.6 and 22 Hz, F-2).The aqueous DMF phase was extracted with ether(3 x 50 cm3) and the combined ether layers were washedwith water (3 x 100 cm3), dried (MgSO,), and evaporatedto give 2-aminoiionafluorobenzophenone (0.53 g), identifiedby i.r.spectroscopy.1,2,3,4-Tetrafluoroacridone (IV) .-Dried potassium fluor-ide (1.5 g) was added to a solution of 2'-amino-2,3,4,5,6-pentafluorobenzophenone4 (111) (1.1 g) in DMF (10 cm3),and the mixture was heated on a steam-bath for 3 h. Thesolution was poured into water (150 cm3) and the precipitatefiltered off and dried. This was shown by t.1.c. to containstarting material and a second component, and was heatedwith carbon tetrachloride (20 The suspension wasfiltered and the solid shown to be 1,2,3,4-tetrafluoro-acridone (IV) (0.23 g), m.p.360°, by i.r. spectroscopy.4 Thefiltrate was evaporated and the residue (0.6 g) shown byt.1.c. to be a mixture of 2'-amino-2,3,4,5,6-pentafluorobenzo-phenone and 1 , 2,3,4-tetrafluoroacridone.methanol (VIII) .-To a stirred suspension of magnesium(0.66 g) in dry ether (30 cm3) was added l-bromo-2,3,4,5-tetrafluorobenzene l3 (6.0 g) in ether (30 cm3). The mixturel3 J. F. Tilney-Bassett, Chem. and Ind., 1965, 693; J. Burdon,D. R. Icing, and J . C. Tatlow, Tetmhcdr.on, 1966, 22, 2541.(lF, ddd, J l , z 22, J1.3 8, J1,4 14.6 Hz, F-l), 73.2 (lF, dt,4-MetJzoxytetrafkuoro~henyl- (2,3,4,5-tetra$uorophenyl)J.C.S. Perkin Iwas stirred and refluxed for 2 h, then cooled to 0 "C andtetraflnoro-p-methoxybenzaldehyde 14 (VII) (6.4 g) in ether(50 cm3) was added.After 16 h at 15 'C, 4~-hydrochloricacid (100 cm3) was added. The ether layer was separatedand the aqueous phase extracted with ether (2 x 100 cm3).Drying (MgSO,) and evaporation of the extracts left aresidue (11.0 g) which was distilled (0.2 mmHg) to give ayellow oil (6.0 g) . This was separated by column chromato-graphy (silica gel; benzene) to give a product which wasrecrystallized from petroleum (b.p. 60-80') to yield a solid(3.0 g), m.p. 56-59'. A sample (1.0 g) of the solid re-crystallized from petroleum (b.p. 60-80") gave the diphenyl-methanol (VIII) (0.63 g), m.p. 59.5-60" (Found: C, 47.0;H, 1.9; F, 42.7.C,,H,F,O, requires C, 46.9; H, 1.7;F, 42.5%), v,, 3 520 (OH), 3 092 (aromatic CH), and 1 498cm-l (fluoroaromatic rings), &If 358, 6 [(CD,),CO] 3.33(lH, s, OH), 4.12 (3H, t, J 1.5 Hz, OMe), 6.4 (lH, s,aliphatic), and 7.68 (lH, m, ArH), [(CD,),CO] 141.1,145.0, 146.1, and 159.7 (lF, lF, 2F, and 4F respectively,all m).(IX) .-A solution of the diphenylmethanol (VIII) (5.25 g) inglacial acetic acid (50 cm3) was oxidized with chromiumtrioxide (4.5 g) a t room temperature for 24 days. Themixture was poured into water (300 cm3) and extractedwith ether; washing, drying, and evaporation gave aresidue (4.98 g) which was recrystallized from perfluoro-1,4-dimethylcyclohexane and sublimed ( 140" ; 12 mmHg) .The sublimate was recrystallized from the solvent usedinitiaIly to afford the benzophenone (IX) (2.0 g), m.p.41.5-42" (Found: C, 36.9; H, 1.0; F, 42.3.C,,H,F,O,requires C, 47.2; H, 1.1; F, 42.7%), Mf 356 (required),vmx (in hexachlorobutadiene) 3 062 (aromatic CH),2 950 (aliphatic CH), 1678 (GO), and 1 640 and 1477cm-I (fluoroaromatic ring); 6 (CDC1,) 4.27 (3H, t, J2.0 Hz, OMe) and 7.37 (lH, m, ArH), 4 (CDCl,) 137.4(lF, dddd, JZt5. 12.5, J4t5. 19.7, J3p5B 3.2, JSe6. 9.3 Hz,F-57, 139.2 (lF, m, F-2'), 143.5 (2F, m, F-2, -6), 146.3(lF, m, F-47, 154,l (lF, t, J 19.7 Hz, F-3'), and 158.0(2F, m, F-3, -5).Attempted Nitration of the Methoxy-octafluorobenzophe-none (IX) .--A mixture of tetramethylene sulphone (7 cm3),fuming nitric acid (0.3 cm3) saturated with boron trifluorideat 0 OC, and the benzophenone (IX) (0.5 g) was heated at65 "C for 3 h.The mixture was then poured onto ice(100 g) and the precipitate (0.26 g) identified by i.r. spectros-copy as starting material. The sulphone-water mixturewas extracted with ether but afforded only the sulphone.Reaction of the Methoxybenzophenone (IX) with SulphuricAcid.-The benzophenone (0.37 g) was dissolved in con-centrated sulphuric acid (10 cm3) and heated at 100 "C for18 h. The mixture was poured into ice-water (70 cm3) andextracted with ether (3 x 40 cm3), and the combinedextracts were dried (MgSO,) and evaporated. The residue(0.36 g) was dissolved in aqueous sodium hydrogen carbo-nate (30 cm3; 10% w/v) and extracted with ether (3 x 20cm3); evaporation of the dried (MgSO,) extracts gave noproduct.The aqueous hydrogen carbonate solution wasacidified and extracted with ether (3 x 50 cm3). Thecombined extracts were dried (MgSO,) and evaporated andthe residue (0.20 g ) was sublimed (60"; 12 mmHg) and14 E. V. Avoskar, P. J. N. Brown, R. G. Plevey, and R .Stephens, J. Chem. SOC. (C), 1968, 1669.15 L. J . Belf, M. W. Buxton, and J . F. Tilney-Bassett, Tetra-hedron, 1967, 23, 4719.2,2', 3,3', 4', 5,5', 6-OctafEuoro-4-methoxybenzo~henonerecrystallized from petroleum (b.p. 60-80") to yield2,3,4,5-tetrafluorobenzoic acid (0.11 g), m.p. 84.5-87'(lit.,15 85.5-87"; lit.,le 92-92.5'), with c0rrecti.r. spectrum.methyl Chloride (X) .-A solution of the diphenylmethanol(VIII) (4 g) in chloroform (18 cm3) and pyridine (1.5 cm3)was treated with thionyl chloride ( 5 cm3) in chloroform(15 cm3).The mixture was refluxed for 3 h, then cooled,and 4~-hydrochloric acid (30 cm3) was added. Thechloroform layer was separated and the aqueous phaseextracted with ether (2 x 50 cm3). The combined chloro-form layer and ethereal extracts were dried (MgSO,) andevaporated under reduced pressure. The residue (4.2 g) waspurified by column chromatography (silica gel; ether) andthe product recrystallized from petroleum (b.p. 60-80')at -18 "C to afford the chloride (X) (3.5 g), m.p. 31.5-33"(Found: C, 45.0; H, 1.5; F, 40.1. C14H5C1F,0 requiresC, 44.6; H, 1.3; F, 40.4%), M+ 398 (one Cl), v,,, 3 080(aromatic CH) and 1649, 1525, and 1490 cm-1 (Auoro-aromatic ring), 6 [(CD,),CO] 7.56 (lH, m, ArH), 6.51(lH, s, CHCl), and 4.1 (3H, t, J 1.6 Hz, OMe): 4 [(CD,),CO](lF, m, F-2'), 144.1 (2F, m, F-2, -6), 155.6 (lF, dt, J4r6p 6,J 20 Hz, F-4'), 156.7 (lF, t, J 20 Hz, F-37, and 158.4(2F, m, F-3, -5).inethane (XI).-The chloromethane (X) (1.0 g) in ethanol(40 cm3) containing palladium-charcoal (10% ; 0.1 g) wastreated with hydrogen.When absorption had ceased thesolution was filtered and evaporated. The residue wasseparated by column chromatography (silica gel ; carbontetrachloride) and the product vacuum-distilled to give asolid (0.7 g) which was recrystallized from petroleum(b.p. 60-80") at - 18" C to afford the diphenylmethane (XI)(0.6 g), m.p. 39.5-40" (Found: C, 48.5; H, 1.9; F, 44.3.C,,H,F,O requires C, 49.1; H, 1.8; F, 44.4y0), M+ 342,vmz 3 080 (aromatic CH), 1 525, and 1 492 cm-l (aromaticring), 6 (CCI,; 100 MHz) 4.02br (ZH, s, CH,), 4.09 (3H, t,J 1.3 Hz, OCH,), and 6.74 (lH, m, ArH), 4 (CCl,) 140.6(lF, dddd, J2'6' 13.3, J3e5e 2.2, J4r5t 20.6, Jg6* 10.5 Hz,F-57, 144.2 (lF, m, F-2'), 146.4 (2F, m, F-2, -6), 156.8(lF, tt, J 3 p 6 p 2.0, J3p4t = J2r31 = 20.1 Hz, F-37, and 159.0(3F, m, F-4', -3, -5).Attempted Nitrations of the Diphenylmethyl Chloride (X)and the Diphenylunethane (XI) .-Attempts were made tonitrate the title compounds (0.26 g) in concentratedsulphuric acid (3 cm3) and fuming nitric acid (1.5 cm3) a t90 "C for 18 h.The products were diluted with water(100 cm3) and the aqueous solution extracted with ether togive an acidic residue from which no identifiable productswere isolated ; starting materials were not recovered.Aminononafluorobenzophenone 1 (I) (0.5 g) in dry methanol(7 cm3) was stirred with a solution of sodium methoxidein methanol (2 cm3; 0.558~) a t room temperature for 12 h.The mixture was then poured into water (100 cm3) and theaqueous solution extracted with ether (3 x 40 cm3).Washing, drying, and evaporation left a residue (0.50 g),which was shown by t.1.c.(silica gel; carbon tetrachloride)to contain three components, one of which had the same RFvalue as starting material. The major component wasseparated by column chromatography (silica gel ; carbontetrachloride) and recrystallized from perfluoro- 1,Li-dimethyl-4-Methoxytetraj3uorofihenyl- (2,3,4,5-tetrafEuorophenyZ) -138.6 (lF, ddd, J 4 .5 ~ 20.8, J 2 ~ 5 t = J5.6. = 10.4H2, F-5'), 143.14-Methoxytetraflumophenyl- (2,3,4,5-tetrafluoroPhenyl) -2-Amino-octafEuoro-4-methoxybenzophenone (V) .- 2-l6 R. J. Harper, E. J. Soloski, and C. Tamborski, J. Org. Chem.,1964, 29, 23851975 1385cyclohesane to afford the methoxy-derivative (V) (0.49 g),m.p. 73-74" (Found: C, 45.6; H, 1.7; F, 40.6; N, 4.0.C14H,F,N0, requires C, 45.3; H, 1.35; F, 41.0; N, 3.8%),m/e 371 (&I+), 204, 195, 176, and 167 (no peaks a t 207, 192,179, and 164), vmx. 3 505, 3 360 (NH,), 1 658 (GO), 1500,and 1465 cm-1 (fluorosromatic ring), 6 (CCl,) 4.18 (3H, t ,J 1 Hz, OMe) and 6.49br (2H, s, NH,), 4 (CCl,) 142.4 (lF, dd,J9,6 11.3. J5,6 22.6 Hz, F-6), 144.3 (2F, m, F-2', -67, 153.2Hz, F-3), 161.8 (2F, m, F-3'.-57, and 170.6 (lF, dd, F-5)(calc.6 4 for 4-methoxy-substitution: F-3, 158.4; F-5,161.0; for 5-methoxy-substitution: F-3, 164.7; F-4,161.0).Halogeszoform-type Cleavage of 2-Amino-octafluoro-4-metlzoxybeizzophenone (V) .-The title compound (0.26 g),ethanol (5 cm3), water (10 cm3), and potassium hydroxide(6 g) were shaken for 4 h. The mixture was then pouredinto water (50 cm3): extraction with ether gave onlyethanol. The aqueous phase was acidified (~N-HC~) andextracted with ether (3 x 50 cm3). The dried (MgSO,)extracts were evaporated to afford a solid which wasrecrystallized twice from water to yield 2-aminotri$uoro-4-methoxybei??oic acid (XII) (0.06 g), m.p. 181.5-182"(Found: C, 43.7; H, 2.7; F, 25.7; N, 6.5.C8H6F3N0,requires C, 43.4; H, 2.7; F, 25.8; N, 6.3%), umx. 3 520and 3398 (NH,), 3300-2OOObr (OH), 1653 (GO), and1460 cm-I (fluoroaromatic ring), 6 [(CD,),CO] 4.1 (lH,J 9.0 Hz, OMe) and 4.7br (lH, s, +NH3), C$ [(CD,),CO]J3,, 2.8 Hz, F-3), and 169.8 (lF, dd, F-5) (calc6 C$ for 4-methosy-substitution: F-3, 157.4; F-5, 168.4; F-6,143.8; for 5-methoxy-substitution: F-3, 163,8; F-4,-4 tlenipted Synthesis of 2-AminotriJluoro-4-methoxybenzoi~Acid.-(a) With aqueous ammonia. Methyl tetrafluoro-4-niethospbenzoate l4 (1.0 g), methanol (6 cm3), and aqueousammonia (1 cm3; d 0.880) were heated in an autoclave at132 "C for 24 h. Pouring into water, acidification, andextraction with ether afforded starting material (0.9 g),identified by i.r.spectroscopy.(b) With lithium arnide. To a stirred suspension oflithium aniide (0.5 g) in ether (10 cm3) a t -70 O C , wasadded methyl tetrafluoro-4-methoxybenzoate (1 .O g) inether (10 cm7. The mixture was then allowed to warmto room temperature, stirred for 24 h, and cooled to 0 "C,and water (40 cm3) was added. Acidification and extrac-tion afforded the tetrafluorobenzoate (1.0 g), identified byi.r. spectroscopy.Nucleophilic Substitution of 0ctaJuoroacridone.-The titlecompound (0.16 g) in freshly distilled dimethyl sulphoxide(7 cm3) at 110 "C was stirred with a solution of sodiuminethoxide in methanol (5 cm3; 1 . 1 3 ~ ) for 30 min. Themixture was cooled and acidified ( ~ N - H C ~ ; 6 cm3). Thebuff-coloured precipitate was filtered off, dried, and re-crystallized from ethanol to give 1,2,4,5,7,8-hexufEuoro-3,6-dimetl~o,yacridone (XIV) (0.07 g), m.p.266-267'(Found: C, 49.8; H, 2.0; F, 31.6; N, 3.9. C15H7F,N03requires C, 49.6; H, 1.9; F, 31.4; N, 3.9%), vm, (hexa-chlorobutadiene) 3 395 (NH and OH), 3 005, 2 960, 2 900(CH), and 1 640 cm-l (GO), Lax. 222.5, 260, 277, and 375nm ( E 17 000, 48400, 23000, and 5 750), 6 [(CD,),SO;84 OCJ 4.07 (t, J 2.0 Hz) (no NH signal owing to exchangebroadening a t high temperature), # (CF,*CO,H internal(lF, t, J 20.3 Hz, F-4'), 160.6 (lF, dd, J 3 , 6 11.3, J3,s 2.4171.3; F-6, 142.1; F-2', -6', 143.6; F-4', 153.6; F-3', -5',142.1; F-6, 135.7; F-2', -6', 143.6; F-4', 153.6; F-3', -5',135.9 (lF, dd, J3,e 12, J5.6 21.5 Hz, F-6), 156.7 (lF, dd,149.7; F-6, 137.4).standard) 70.5 (IF, dd, J1,, 21.4, J1.4 14.7 Hz, F-l), 76.5(lF, dd, J2.4 2.7 Hz, F-4), and 87.0 (lF, dd, F-2).Heptufluoro-3-methoxyacridone (VI) .-To a solution of2-amino-octafluoro-4-methoxybenzophenone (V) (0.6 g) indry DMF (10 cm3) was added potassium fluoride (0.3 g),and the mixture was heated on a steam-bath for 8 h.Theproduct was poured into water (160 cmS) and the yellowprecipitate (0.46 g) filtered off and dried. The solid wasseparated by column chromatography [silica gel ; carbontetrachloride-ether (5%)] to give the polyfluorobenzo-phenone (0.18 g), identified by i.r. spectroscopy. Thecolumn packing was Soxhlet extracted with ethanol, theethanolic solution was evaporated, and the solid residue(0.23 g) was recrystallized from ethanol to yield he$ta-Jluoro-3-methoxyacridone (VI) (0.19 g), m.p.247.5-248.5"(Found: C, 47.6; H, 1.4; F, 38.2; N, 3.6. C14H,F7N0,requires C, 47.9; H, 1.1; F, 37.9; N, 4.0%), vF 3 180,1 639 (GO), 1 487, and 1 460 cm-I (fluoroaromatic rings),Amx- 221.5, 253.5, 277, 349, and 385 nm (E 20 875, 41 076,14 600, 6 400, and 5 900), 6 [(CD,),SO; 80 "C] 4.07 (t, J2.0 Hz, OMe), 4 [(CD,),SO; CF,*CO,H internal standard](lF, dd, J1,, 20, J1.4 13.5 Hz, F-1), 76.5 (2F, m, F-4, -6),J2.4 2 Hz, F-2), and 93.5 (lF, dt, J 3.3 and 22 Hz, F-7).Nucleophilic Substitution of Heptafluoro-3-methoxyacri-done (VI) .-To a solution of the title compound (0.12 g) indry dimethyl sulphoxide (5 cm3) a t 80 "C was added sodiummethoxide in methanol (5 cm3; 1.13~).The mixture wasstirred for 20 min, then cooled and acidified (~N-HC~,5 cm3). The precipitate was filtered off, dried, and re-crystallized from ethanol to give hexafluoro-3,6-dimethoxy-acridone (XIV) (0.04 g), shown by m.p., mixed m.p. (266-266"), and i.r. and n.m.r. spectroscopy to be identical withthe compound obtained by the reaction of methoxide ionwith octafluoroacridone.9-Chloro-octafluoroacridine (XV) .-A mixture of octa-fluoroacridone (0.4 g) and phosphoryl chloride (20 cm3) washeated a t 125-130 "C for 3 h. Excess of the reagent wasdistilled off, the residue was dissolved in chloroform (40cm3), and the solution was poured into a mixture of ice(50 g) and aqueous ammonia (80 cm3; d 0.880). Thechloroform layer was separated and the aqueous layerextracted with chloroform (2 x 50 cm3).The combinedchloroform solutions were dried (CaCl,) and evaporated toleave a residue which was sublimed (130"; 12 mmHg).The sublimate was recrystallized from petroleum (b.p.6@-80") to afford 9-chloro-octafluoroacridine (XV) (0.28 g),m.p. 164-165" (sealed tube) (Found: C, 43.6; F, 42.2;N, 4.3. C13C1F,N requires C, 43.6; F, 42.5; N, 3.9%),M f 359 (one CI), vmx. 1 680, 1 480 (fluoroaromatic rings),1358, and 1066 cm-l, 9 (CDCI,) 140.9 (lF, t, J 16.9 Hz),148.6 (lF, t, J 18.3 Hz), 149.3 (lF, t, J 16.9 Hz), and 152.8(lF, t, J 16.9 Hz), A,, 258.5, 367.0, 385.0, and 410 nm(E 94 600, 3 750, 4 350, and 3 465).Attempted Preparation of Nonafluoroacridine.-Potas-sium fluoride (1.0 g) in tetramethylene sulphone (15 cm3)was dried by azeotropic distillation with benzene, and 9-chloro-octafluoroacridine (0.37 g) was added.The mixturewas stirred a t 125 "C for 20 h, and acquired an intense redcolour. The products were poured into ice-water (150 cm3),and the mixture was extracted with ether (3 x 60 cm3).The combined extracts were washed with water (3 x 100cm3), dried (MgSO,), and evaporated and the residue wasseparated by column chromatography on silica gel.70.5 (lF, ddd, J5.8 14.4, 1 6 . 8 8.5, J7.8 21.6 Hz, F-8), 72.080.5 (lF, ddd, J5.7 3.3, J5.6 22 Hz, F-5), 87.5 (IF, dd1386 J.C.S. Perkin IImpurities were removed by elution with 5% ether incarbon tetrachloride, the major product being then elutedwith ether to afford octafluoroacridone (0.29 g), identifiedby m.p.and i.r. spectroscopy.Sodium 0ctafluoroacridonate.-To a suspension of octa-fluoroacridone (0.1 g) in water (10 cm3) was added sodiumhydroxide (0.75 g) . The mixture was stirred to dissolve thesodium hydroxide, and the suspension filtered. The yellowresidue was washed with water and dried to afford sodiumoctafluoroacridovaate (0.09 g), m.p. 360" (Found: C, 43.5;F, 40.3; X, 3.8. C13F,NNa0 requires C, 43.2; F, 42.1;N, 3.9%), no i.r. peaks (in hexachlorobutadiene) character-istic of NH or OH, hinds. 248, 333, 347, 370, 388, 407, and 431nm (s 36 690, 5 564, 9 833, 4 110, 6 306, 7 037, and 4 550).Sodium 1,2,4,5,7,8-Hexafluoro-3,6-dimethoxyacridonate.-To a suspension of 1,2,4,5,7,8-hexafluoro-3,6-dimethoxy-acridone (0.1 g) in water (10 cm3) was added sodium hydr-oxide (0.75 g) and the mixture was stirred. The yellowprecipitate was filtered off and dried to afford the acridonate(0.09 g), m.p.360" (Found: C, 46.7; H, 1.7; F, 27.2; N,3.6. C,,H6F,NNa03 requires C, 46.8; H, 1.6; F, 29.6;N, 3.6%), no i.r. peaks (in hexachlorobutadiene) character-istic of OH or NH, &= (EtOH) 262, 282, 350, and 375 nm(s 40 660, 18 860, 3 536, and 5 008).Reactions with Sulphuric Acid.-(a) Methyl tetrafiuoro-4-nzethoxybenzoate. The benzoate (1 .O g) in concentratedsulphuric acid (10 cm3) was heated a t 100 "C for 4 h, thenpoured into water (100 cm3). The solution was extractedwith ether (3 x 50 cm3), and the combined extracts driedMgSO,) and evaporated. The residue was distilled invacuum to afford 2,3,5,6-tetrafluorophenol (0.8 g), identi-fied by i.r. and n.m.r. spectroscopy, and by formation of thetoluene-f-sulphonate, m.p. 79-40' (lit.,, 80-81")(b) Methyl Pentafluorobenzoate. The methyl benzoate(0.5 g) was heated on a steani-bath with concentratedsulphuric acid (10 cm3) for 3k 11, and the products werepoured into water (100 cm3). The aqueous solution wasneutralized (aqueous NaHCO,) and extracted with ether(3 x 50 cm3). The combined extracts mere dried (MgSO,)and evaporated and the residue (0.09 g) w-as identified byi.r. spectroscopy as starting material. The aqueous phasewas acidified (~N-HC~) and extracted with ether (3 x 50cm3). The combined ether layers were dried (MgSO,) andevaporated to leave a residue shown to be pentafluoro-benzoic acid (0.39 g), m.p. 100' (lit.,17 101.5-102") by i.r.spectroscopy.The title compound (1 .O g)in concentrated sulphuric acid (10 cm3) was heated a t100°C for 3+ 11. The mixture was poured into ice-water(100 cm3) and the solution extracted with ether (3 x 50an3). The ether layers were dried (MgSO,) and evaporatedand the residue was distilled from P,O, under reducedpressure to give 2,3,5,6-tetrafluorophenol (0.72 g) , identifiedby i.r. spectroscopy.A mixture of pentafluoroanisole(1.6 g) and concentrated sulphuric acid (10 cm3) was treatedas described above to afford, after evaporation of theethereal extracts, a residue, which was vacuum-distilledfrom P,O, to yield pentafluoroanisole (1.3 g) only.(c) 2,3,5,6-Tetra$uoroanisoZe.(d) Pentafluoroanisole.We thank Dr. J. Burdon for measurement of n.m.r.spectra and Dr. J. Majer for mass spectral determinations.[5/056 Received, 9th January, 1975117 B. Gethin, C. R. Patrick, M. Stacey, and J. C. Tatlow,Nature, 1959, 183, 588
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