Fluorinations with potassium tetrafluorocobaltate(III). Part VI. Fluorination of pyridine and 4-methylpyridine

摘要

1732 J.C.S. Perkin IFluorinations with Potassium Tetrafluorocobaltate( 111). Part V1.l Fluori-nation of Pyridine and 4-MethylpyridineBY Paul L. Coe,' J. Colin Tatlow, andBox 363, Birmingham B15 2TTMichael Wyatt, Chemistry Department, University of Birmingham, P.O.Pyridine has been fluorinated over KCo"F, to give a mixture largely of ring-opened products. The main com-ponents isolated were (Z)-undecafluoro-2-atahex-2-ene (I), (Z)-2H-1 -bistrifluoromethylaminotetrafluoroprop-1 -ene (11), (E) -2H-1 -bistrifluoromethylaminotetrafluoroprop-1 -ene (111), (Z) -5H-decafluoro-2-azahex-2-ene(IV), (2Z,4€) -4H,5H-heptafluoro-2-azahexa-2,4-diene (V), (22.42) - 5H-octafluoro-2-azahexa-2.4-diene (VI),(2Z,4€)-5-bistrifluoromethylamino-octafluoro-2-azahexa-2,4-diene (VII), (2Z,4Z)-5-bistrifluoromethylamino-octafluoro-2-azahexa-2.4-diene (VIII), and 3H-1 -difluoromethylheptafluoropyrrolidine( IX).In a similarmanner, fluorination of 4-methylpyridine gave the analogous compounds (Z) -5-trifluoromethyldeafluoro-2-aza-hex-2-ene (X). (Z) -5-trifluoromethyloctafluoro-2-azahexa-2,4-diene (XI), (Z)-5-methyldecafluoro-2-azahex-2-ene (XII). and (Z) -5-difluoromethyldecafluoro-2-azahex-2-ene (XIII) as major components.IN previous papers in this series we have describedthe fluorinations of benzene,2 naphthalene: ketones:and esters and acid fluorides by KComF,, the resultsdiffering significantly from those obtained using COF,.We have now extended our studies of the former reagentto the fluorination of pyridine and 4-methylpyridine.Although pyridine and its derivatives have suc-cessfully been fluorinated by the electrochemicalmethod to give polyfluoropiperidine, and variouspolyfluoropyridines were prepared by exchange pro-cesses,' attempts to fluorinate pyridines by usingtransition metal fluorides have given poor results.Pyridine and COF, at 360" gave8 perfluoropiperidineas the only isolable product in 0.2 yield, 2,6-dimethyl-pyridine givingg a 5 yield of the correspondingpexfluoropiperidine. In related work lo 2-fluoropyri-dine with elemental fluorine yielded a complex mixtureof breakdown products and a little perfluoropiperdine.We have found that fluorination of pyridine overthe new reagent KCoF, at 210-230" gave a complexmixture of products containing nine main com-ponents.Separation of the mixture was difficultsince some decomposition with deposition of crystalsoccurred on standing even for a short time at roomtemperature, and also normal fractional distillationgave rise to extensive decomposition. The mixturewas finally fractionated into cuts each of which con-tained a substantial percentage of one of the majorcomponents, by using rapid take-off and careful heatingon an oil-bath, so as to keep the flask temperature to aminimum. Further purification could be carried outby g.1.c. and the nine major components were all iso-lated (see the Table). The crystals formed on decom-position were identified by elemental analysis andspectroscopy as 4,4,4- t rifluoro-N- t rifluoromet h y lcr o t on-1 Part V, J.Burdon, J. R. Knights, I. W. Parsons, and J. C.2 P. L. Coe, R. G. Plevey, and J. C. Tatlow, J. Chem. SOC. (C),3 P. L. Coe, R. M. Habib, and J. C. Tatlow, in preparation.4 R. D. Bagnall, P. L. Coe, and J. C . Tatlow, J.C.S. Perkin I,6 R. D. Bagnall, P. L. Coe, and J. C. Tatlow, submitted for6 J. H. Simons, J. Electrochem. SOC., 1949, 95, 47.7 R. D. Chambers, J. Hutchinson, and W. K. R. Musgrave,Tatlow, J. Fluorine Chem., in the press.1969, 1060.1972,2277.publication in J . Fluorine Chem.J . Chem. SOC., 1964, 3673.amide which presumably arises from hydrolysis ofcompound (V) (see below).The lowest boiling component was shown by compari-son of its i.r. and n.m.r. spectra to be the known undeca-fluoro-2-azahex-2-ene (I) with a chemical shift valuefor the imino-trifluoromethyl groups in agreement withthat given by Haszeldine l1 rather than that of Muller.12On the basis of the 19F n.m.r. spectrum we assign thestereochemistry of the CF,N=CF double bond as 2.13The reasoning follows that of Ogden and Mitsch14for compounds containing the CF,N=CF group.Byanalogy with fluoro-olefins, where the CF, groupsshowed a signal in the range 57.3-57-7 p.p.m. (shiftrelative to CCGF) with a doublet splitting of 13.3-14.3 Hz they ascribed cis (2) stereochemistry, whilstwhere peaks occurred at 54-2-56.8 p.p.m. with a coup-ling of ca. 6 Hz, trans ( E ) stereochemistry was assumed.In compound (I), resonance occurred at 57.3 p.p.m.with a coupling of 14 Hz, indicating that the compoundhad 2 stereochemistry. This pattern was repeatedfor all the imines isolated from this fluorination.The i.r.spectrum of the second component isolated(11) indicated that there was no CF,N=CF groupsince the band at ca. 1770 cm-l14 was absent, but aband at 1725 cm-l suggested a CHKF group. Oxida-tion of (11) with potassium permanganate in acetoneafforded trifluoroacetic acid, identified as its S-benzyl-isothiouronium salt, suggesting the presence of a vinylicCF, group. The mass spectrum gave a peak at mle246 and a fragmentation pattern consistent with thestructure (CF,),NCF=CHCF, (11). This was supportedby elemental analysis, and lH and laF n.m.r. spectralanalysis. The stereochemistry of the double bond wasindicated by the n.m.r.spectra. The olefinic protonshowed two couplings, 21.8 and 6-5 Hz, the value 21.8* R. N. Haszeldine, J. Chem. SOC., 1960, 1966.@ R. N. Haszeldine, J. Chem. SOC., 1960, 1638.lo R. E. Banks and G. E. Williamson, J. Chem. SOC., 1966, 816.l1 R. E. Banks, W. M. Cheng, and R. N. Haszeldine, J. Chem.l2 N. Muller, P. C. Lauterbauer, and C. F. Svatos, J. Amer.la J. E. Blackwood, C. L. Gladys, K. L. Loering, A. E. Petranca,l4 P. H. Ogden and R. A. Mitsch, J. Amer. Chem. Suc., 1967,SOC., 1963. 3407.Chem. SOC., 1967. 79, 1807.and J. E. Rush, J. Amer. Chem. Soc., 1968, 90, 509.89, 60071974 1733lying in the range expected for a trans HF system.15The 19F spectrum showed couplings for the CF, groupof 17.8 (coupling with the vinylic fluorine atom) and6.6 Hz (see above in the lH spectrum) due to geminalCF,-H coupling.This latter corresponds well to theof 6.3 Hz.(CF ) N p 33 2 ,c=c, value found l6 inProduct Yield (yo) *4-Methylp yridineH/ HWe thus assign 2 stereochemistry to compound (11).The third component isolated (111) showed verysimilar mass spectral, ix., and analytical data to com-pound (11) above, but showed differences in the 1Hand 191; n.m.r. spectra. Oxidation as above againafforded trifluoroacetic acid. The olefinic protonComposition of fluorination mixture from KCOI~F,and pyridine or 4-methylpyridineProduct Yield () *PyridineFCF2* C FH * C F3ck / (IY) N=C,(PICF3,N /F‘C=CH/CF3NF/ =C‘CF’/LFCSHResidue15.46.35.611.58.219.41.51.42.128.66.9“=C 9.8CH3FC’17.610.1CF2.CFI*CF3CH 5Residue 65.9* Based on isolated products.showed couplings of 6 and 3-25 Hz whilst in the 19Fspectrum the CF, group and olefinic fluorine atom gavecomplex peaks.However, on the basis of the lHspectrum it is clear that a geminal CF,-H coupling(6 Hz) is present, and the 3.25 Hz coupling is consistentwith a cis-H-F grouping.15 Thus compound (111) isassigned E stereochemistry.The fourth component (IV) showed an i.r. band at1770 cm-1, indicating the presence of a CF3N=CFgroup, confirmed by the 19F n.m.r. spectrum whichshowed the characteristic peak for the CF, group at58.3 p.p.m. with a 14 Hz coupling as discussed above.The mass spectrum and elemental analysis data sug-gested a structure CF,N=CFC,HF,.The 19F n.m.r.spectrum showed a peak at 213.2 p.p.m., correspondingto a -CFH group rather than a -CF,H group. A 5H-rather than a 4H-arrangement is preferred on the basisof coupling patterns * so the structure of (IV) is (2)-CF3N=CFCF2CHFCF3.The fifth and sixth components (V) and (VI) weredifficult to separate, but by careful preparative g.1.c.each was obtained pure. Compound (V) showed twoi.r. bands at 1730 and 1670 cm-1 assigned to CF,N=CF-and -CH=CH- respectively. Elemental analysis andmass spectral data suggested C,H,F,N as the empiricalformula indicating (V) to be a hexadiene. The lHn.m.r. spectrum showed a complex system attributable* The 1H and 1*F n.m.r.data are listed in a Supplementary16 J. W. E,msley, J. Feeney, and L. H. Sutcliffe, ‘High Resolu-16 J. Freear and A. E. Tipping, J. Chem. SOC. (C), 1968, 1096Publication : see the Experimental section.tion N.M.R., Pergamon, Oxford, 19661734 J.C.S. Yerkin Ito an ABMX, system li from which JAB could be de-termined as 16 Hz. This value suggests that thevinylic hydrogen atoms are in the E arrangementon the basis that J H x (trans) in olefinic compoundsusually falls in the range 13-18 Hz. The CF,N=CFgroup showed the typical 14 Hz coupling noted inall the previous compounds and is characteristic of the2 configuration. Thus (V) is assigned the structure(22,4E)-4H,5H-heptafluoro-2-azahexa-2,4-diene. Com-pound (VI) showed bands in its i.r.spectrum whichsuggested the presence of CF,N=CF- (1740) and -CF=CH(1690 crn-l) groups. Mass spectral and analyticaldata indicated that (VI) was C,HF,IC. The lH n.m.r.spectrum indicated that the product contained a singlevinylic proton coupled to a geminal CF, group (7 Hz)and to a trans-fluorine atom (26 Hz), and the lgF n.rn.r.spectrum confirmed this and indicated the character-istic coupling for the CF,N=CF- group; (VI) is thusassigned as (22,a.Z) -5H-octafl uoro-2-azahexa-2,4-diene.Compounds (VI I) and (VI I I) were very similar.Mass spectral and analytical data suggested an em-pirical formula C7F14N2; the lH n.m.r. spectrumconfirmed to absence of protons. The 19F n.m.r.spectrum indicated that each compound had the(2)-CF,N=CF group. The remaining signals suggestedthe presence of CF,, =CF, and (CFJ2K groups. Thus(VII) and (VIII) appeared to be isomers differing in theconfiguration about a double bond and to have thegross structure CF,N=CFCF=CCF,N (CF,),. Analysisof the coupling patterns found for the vinylic CF,and F groups, showed a doublet for the CF, group in(VII) (JFF 17 Hz) but a complex pattern for the CF,group in (VIII) whilst the vinylic F atom in (VII)gave a doublet of quartets JFF(d) = JFp(q) = 17 Hzbut a broad singlet in (VIII).On this basis (VII) isassigned the E configuration about the C=C bondwhilst (VIII) has the 2 arrangement.The final component isolated (IX) was shown byanalytical and mass spectral data to be C,H,FgN witha breakdown pattern very different from that of com-pounds (1)-(VIII) suggesting a different type ofstructure. The lH n.m.r.spectrum showed a signalattributable to a CF,H group (JHF 58 Hz) and anotherproton doubly split ( J H F 51 Hz). The 19F n.m.r.spectrum also showed the CF,H group but gave a quintetsplitting in addition to the large doublet expected forthe H-F coupling. Further, the spectrum revealedtwo AB type signals and a collapsed AB, each corre-sponding to the fluorine atoms. There was also a highfield signal due to a single fluorine atom (CFH group).This suggested that (IX) could be l-difluoromethyl-3H-heptafluoropyrrolidine, and this was subsequentlyconfirmed in an independent preparation by fluorin-at ion of N-met h ylp yrrole. l8The original fluorination mixture also containedl7 J.Burdon, personal communication.P. L. Coe, P. Smith, and J. C. Tatlow, unpublished work.lB P. L. Coe, A. G. Holton, and J . C. Tatlow, unpublishedwork.2o A. J. Edwards, R. G. Plevey, I. J . Sallomi, and J . C. Tatlow,1.C.S. Chem. Comm.. 1972. 1028.a high boiling fraction now shown l9 to contain severalpolyfluoropyridines. The compounds isolated from thisfluorination are of interest, as is the route by whichthey are formed. In an attempt to relate positionsin the ring-opened products to those in pyridine, wenext fluorinated 4-methylpyridine under essentiallythe same conditions. '4 complex mixture resulted,since CH,, CH,F, CF,H, and CF, groups can be formedfrom the methyl group. However, four major com-ponents, constituting 45-50 of the mixture wereisolated.By a combination of analytical and spectralmeasurements, applying the arguments used above(see Experimental section for details) these were as-signed structures (X)-(XIII) (see Table). Thus, the4-methyl group in the starting material ends up in theposition in all the products isolated.The reaction pathways which give rise to these pro-ducts are not yet understood. Three different speciesare formed, polyfluor~pyridines,~~ the open-chain com-pounds described herein, and the ring contractedAT-methylpyrrolidine derivative. Fluorination of pyri-dine and methylpyridines with caesium tetrafluoro-cobaltate(m) affords 2o polyfluoro-pyridines and -N-methylpyrrolidines, the latter being major products,but no open-chain compounds have been detectedso far.In the previous fluorination of aromatic compoundswe have postulated that in the initial stages of thereaction the transition metal fluoride, e.g.COF,, acts asan oxidising agent to produce radical cations by attackon the x ~ y s t e m , l ~ ~ ~ ~ ~ very much in the manner postulatedfor the formation of phenols from aqueous cobalticsalt oxidation of arenes. The radical cations are thenassumed to be attacked by fluorine atoms or fluorideions to lead either by loss of a proton or by furtheroxidation and loss of a proton to aromatic compounds,in this way by successive oxidations and reaction ofthe radical ions to explain the formation of the observedproducts.Application of this analysis to the fluorinationof pyridine suggests that 2,3,5,6-tetrafluoropyridineshould be a key intermediate in the fluorination. Thisisomer is found as a significant product in the higherboiling fractions of pyridine-KCOF, fluorination l9and it has subsequently been shown that on fluorinationit leads to the expected products.19Further support - for this idea comes from electro-chemical methoxylation of 2,6-dimethoxypyridine whichleads to 2,3,5,6-tetramethoxypyridine and 2,3,3,6,6-pentamet hoxyazacyclohexa-1 ,4-diene.22 This lattercompound corresponds to 1,1,4,4-tetrafluorocyclohexa-1,4-diene found in the fluorination of benzene withKC OF,.^Pyrolyses of perfluorinated heterocycles with N-Fbonds, e.g. perfluoropiperidine, have been re-e.g.__t C6H5F _t P-c6H4lT2. I t iS possible?* J . Burdon, I. W-. Parsons, and J. C . Tatlow, Tefvahadrolz,22 N. L. Weinberg and E. A. Brown, J . Org. Chem., 1966, 31,1972, 28, 43.40541974 1735ported,lO,ll*B and open-chain products and perfluoro-N-methylpyrrolidine were formed. -4lternative freeradical mechanisms were proposed for these processes.However, we have so far not detected any cyclic pro-ducts containing X-F bonds in our fluorination mixturesand since the reaction temperatures we have used aremuch lower than those used in the pyrolyses, suchmechanisms may well not be operating.The gross structures of products (I), (1V)-(VI), and(X)-(XIII) obtained from pyridine and 4-methyl-pyridine indicated the rupture of the 2,3 bond in thering to be important. It seems possible that thisoccurs following the formation of an X-C3 bond to giverise to the X-methylpyrrolidine (IX) obtained.Pro-ducts (VII) and (VIII) presumably arise by the in-corporation of (CFN (via (CF,),NH? into a C-N-C,unit (VI)?. Compounds (11) and (111) might arisefrom re-incorporation in a different way of a (CF,),Nunit into the C, unit left when it is formed, or couldcome from breakdown of the orginal heterocyclic ringin a different way.ESPERJMESTAL,4pparutus.-Fluorinatio1is were carried out in a con-ventional reactor, as previously described,, containingpotassium tetrafluorocobaltate(II1) (6.5 kg) . Preparativeg.1.c. utilised two columns: Unit A; dinonyl phthalate-Celite 1 : 2 (488 x 3-5 cm), and Unit B; dinonyl phthalate(920 x 1 cm), on a Pye series 104 instrument.The lHand l9F n.m.r. data of compounds (11)-(XIII) are listedin Supplementary Publication No. SUP 21025 (5 pp.).*Fluorination of Pyridine.-In a typical run, pyridine(100 g) was added t o the reactor at 210-230' in a streamof nitrogen (10 1 h-l) over 3 h. After the addition, nitrogenwas passed for a further 2 h. The effluent gases werepassed through a sodium fluoride pellet trap at 85-90'and then collected in a glass trap cooled in liquid air t ogive products (145 g). After a short time crystals ap-peared in the fluorination mixture. Sublimation in vacuoafforded 4,4,4-trijhoro-N-tri~uoromethyZcrotonamide, m.p.122-123" (Found: C, 29.0; H, 1.5; F, 55.6; X, 6.8.C,H,F,NO requires C, 29.0; H, 1.4; F, 55.1; N, 6-804,),7 -0.1 (lH, s, CF,NH) and 3-12 (2H, complex, -CH=CH-),l9F n.m.r.57.9 (d, J H F 3 Hz, CF,-NH) and 66.2 p.p.m.(rel. t o CC1,F) (d, J H ~ 5.5 Hz, CF,-CH=).Fractional Distillation.-The products (576 g) from fourfluorinations were filtered through layers of sodium fluorideand magnesium sulphate and then carefully distilledthrough a vacuum jacketed column (122 x 2.5 cm) packedwith Dixon gauze rings to give the fractions 1-6 describedbelow; at ca. 70" degradation occurred and fractions 7(97 g) and 8 (49-9 g) were obtained by distillation in vacuo;a residue (196 g ) remained.Isolation of Products.-Fraction 1 (b.p. 20°. Analyticalg.1.c. indicated a complex mixture of products containingfour major components. Fractionation as before of204 g of the mixture gave three fractions, 1, b.p. <65",66-8 g; 2, b.p. 65-45', 68.8 g ; and 3, b.p. 85-95',31.1 g; pot residue 30.3 g. A portion of fraction 1 wasseparated into its major components in a qualitativemanner t o give (i) (2) -5-trifEzcoromethyZdecu~~oro-2-azahex-2-ene (X), b.p. 62.5' (Found: C, 21.4; F, 74~6. C,F,,Nrequires C, 21.6; F, 74.2), vmax. 1770 cm-l (-CFN-),m/e 333 (MT), 314 (C,Fl,N+t), 226 (C,F,N+), 181 (C4F,+),145 (C,F,N+), and 114 (C,F4Nf), and (ii) (Z)-l$-trif2iroro-rnethylocta~uor0-2-azuhexa-2~4-diene (XI), b.p. 65" (Found :C, 24.2; F, 70.4. C,FllN requires C, 24-4; F, 70.9),vuX. 1700 (-CFC) and 1770 cm-l (CWN-), nz/e 295 (M+),276 (C,Fl,Nf), 188 (C,F,Nf), 181 (C4F,+), 150 (C,F,+), and114 (C2F4Nf). Similarly a portion of fraction 2 gave(i) compound (XI) ; (ii) (2)-5-methyldecuflzoro-2-uzuhex-2-ene ( X I ) , b.p. 76.5' (Found: C, 25-9; H, 0.8; F , 68.5;N, 5.3. C,H,F,,N requires C, 25.8; H, 1.1; F, 68.1;N, 5.6), v,, 1770 cm-l (-CFN-), m/e 260 (M - 19),165 (C4H3F,+), 145 (C,H,F,+), 115 (C,H,F,+), and 114(C,F4Nf) ; and (iii) (Z)-~-di=fluoromethyl~ecu~uoro-2-uzu~ex-2-ene (XIII), b.p. 79.5' (Found: C, 22.8; H, 6.9; F,72.7; N, 4.0. C,H,Fl,N requires C, 22.8; H, 0.3; F,72.4; N, 4.5), vmx 1775 cm-l (-CF="), m/e 296 (M -19), 246 (C,HF,N*), 164 (C,F,N+), and 114 (C,F4Nf).4/082 Received, 17th January, 1974