摘要:
1977 1365Condensation of Perfluoroalkyl Iodides with Unsaturated NitrogenCompoundsBy Danidle Cantacuz&ne,* Claude Wakselman, and Rdgine Dorme, C.N.R.S.-C.E.R.C.O.A. 2, rue HenryDunant, 94320 Thiais, FranceCondensation of enamines with perfluoroalkyl iodides yields a-perfluoroalkyl ketones. An intermediate charge-transfer complex between an iminium iodide and the perfluoroalkyl iodide has been detected. The reaction has beenextended to a-alkoxy-enamines, ynamines, and pyrroles. It is rapid and uncatalysed for many simple enamines ;others require U.V. light.IN a preliminary report we described a simple, generalmethod of introducing a perfluoroalkyl chain a to acarbonyl group. The reaction involved addition of aperfluoroalkyl iodide (R,I) to an enamine under U.V.irradiation in an inert solvent.In this paper theexperimental procedure, the nature of the intermediates,and the extension of the reaction to other unsaturatednitrogen compounds are described. Furthermore weshow that, in contrast to other unsaturated systemsJ2enamines react with perfluoroalkyl iodides very rapidlyat room temperature, without U.V. irradiation orI I i, R F ~ I IR-CZC-N- - R-C-C=O1 1 , H30 IR FP a linitiator. Photochemical and thermal reactions ofcarbon tetrachloride with enamines, giving a-dichloro-methylene ketones or aldehyde^,^ have been reported.No precise mechanism for the radical ieactions ofenamines has been proposed. As suggested for thereaction of methylene iodide with enediamines,5 it mayreasonably be assumed that a radical cation (A) isformed ; with perfluoroalkyl iodides a perfluoroalkylradical Rg' is obtained which attacks the P-carbon atomto give the iminium iodide (B) (Scheme 1).Howeverin view of the rapidity of the condensation it is morelikely that the reaction proceeds through a conventionalchain mechanism (Scheme 2). An experiment describeddue to the presence of a charge-transfer complex betweenthe amino-group of the enamine and RFI, leading toeasier formation of the radical cation (A) and thus ofI l l I l lR-C=C-N: + R F I R-C=C-N: RF' + I' I t II l l RF' I l lI l l ' IR FR-C-C=N' 1 - - R-C-C=N'( 6 ) ( A )SCHEME 1I l l I l l1 ' 1RF' + R-CZC-N: - R-C-C-NR FI l l I l lI I I l lRF I R FRF' + R-C-C-N - R-C-C=N* I' +( B 1SCHEME 2RF'.Such complexes between amines and RFI arewell knownagFavourable conditions for introducing an RF groupare specified; enamines in which R is alkyl or H reactin high yield without U.V. irradiation or radical initiator/ C H 2 R 2R' CH=C (CH 2 R 2 1 * N 3 2 R F R I C H . C ?7below extending the reaction to ynamines providessupport for the chain mechanism.Perfluoroalkyl iodides condense with enamines morereadily than does carbon tetra~hloride.~ This may beD. Cantacuzbne and R. Dorme, Tetrahedron Letteys, 1975,2031. * (a) W. A. Sheppard and C. M. Sharts, ' Organic FluorineChemistry,' Benjamin, New York, 1969; ( b ) R. N. Haszeldineand B. R. Steele, J . Chem. Soc., 1953, 1199; (c) N. 0. Brace, J .Org.Chem., 1962, 27, 3033; 1967, 52, 430.in contrast to enamines in which the nitrogen lone pair isdelocalized (R = Ph or COR') ; moreover the reaction isconsiderably slowed if the starting materials are notpure enough (traces of oxygen).J. Wolinsky and D. Chan, Chem. Comm., 1966, 567.E. Elkik and P. Vaudescal, Comfit. rend. , 1967,264C, 1779.C. F. Hobbs and H. Weingarten, J . Ovg. Chem., 1974,89,918.(a) R. N. Haszeldine, J . Chem. SOL, 1963, 2622; (b) N. F.Cheetham, I . J. McNaught, A. D. E. Pullin, Austral. J . Chem.,1974, 27, 987, 1009 and references herein1366 J.C.S. Perkin IA new type of charge-transfer complex between an vary from 45 (CF,) to 65% (C6FI3), providing thatiminium iodide and a perfluoroalkyl iodide has been starting materials are freshly ‘distilled under argonTraces of oxygen or of a radical inhibitor such as di-R ;C F =C R1* C 0 e C H R 2 phenylpicrylhydrazyl slow the reaction and decrease the w RFR CH.C0.CH2R base * ( 3 1 .- -H30’(4 1 ( 5 1a; R1 = R 2 = M e R F = C F 3c ; R1 = R 2 = M e R F = C z F 5b; R1R2 = [CH213 RF = C F 3d; R1R2 = [CH213 R F = C z F 5e; R1 = R 2 = M e R F = C,F,f ; R1 = R 2 = M e RF = c 6 F 1 39; R1R2 = [CHZ], R F = C6F13detected. Finally an extension of the above reaction toz-alkoxy-enamines, ynamines, and pyrroles is described.Enamirtgs derived from Simple Ketones and AZdehydes;ryields.During the condensation of the starting enamine withRFI in an inert solvent (pentane) and providing that noadditional amine is used to trap HI, an abundantprecipitate (C) is rapidly formed which is not theiminium iodide of type (B) observed in the case of iso-butyraldehyde.The analytical figures for (C) corre-spond to a stoicheiometric mixture of enamine, HI, andRFI. Scheme 3 illustrates a typical experiment. Thechemical characteristics of (C) are those of the productof a reversible association between one molecule of animinium iodide (with no perfluoroalkyl group) and onemolecule of1RFI. Heated at 110 “C under vacuum,* R F IO N 3 + I H - 4 2 ( C )-RFII ’( B )SCHEME 3Formation of a Charge-transfer CompZex.-2-Methyl- (C) yields RFI (yield 70%) and the iminium iodide (B),propenylpyrrolidine reacts easily with perfluorohexyl whereas (B) , synthesized independently, forms theiodide. complex (C) when in suspension in a pentane solutioncontaining RFI.Hydrolysis of (C) produces a mixtureof cyclohexanone and perfluoroalkyl iodide (yield 80%).The physicochemical data of (C) are in agreement withEF - a charge-transfer complex. The U.V. spectrum displaysabsorption at 290 nm (cf. ca. 220 nm for an enamine or p+an iminium salt 7), the position of which depends on theI’ ( C 1 nature of the solvent and of the amino-group (seehydrolysis affords the a-perfluorohexyl aldehyde (2) in Experimental section). The n.m.r. spectrum of (C)In this case the iminium iodide (1) is formed; oa-60% yield.Enamines derived from simpleshows no vinylic proton. The fluorine n.m.r. spectrumshows a signal at 66 p.p.m.(to high field of CFC1,) for enolizable ketones, inpentane solution, condense rapidly with RFI at roomtemperature, without irradiation or initiator, affordingperfluoroalkyl enamines (3a-g) ; the yields are muchhigher if an additional tertiary amine is used to trap HI.a-Perfluoroalkyl enamines (3) are hydrolysed, as ex-pected, to a-perfluoroalkyl ketones (4) [the lattercontain traces of ap-unsaturated ketones ( 5 ) ] . Yields(a) A. G. Cook, ‘ Enamines: Synthesis, Structure, andReactions,’ Dekker, New York, 1969; (b) G. Opitz, H. Hellman,and H. W. Schubert, Annalen, 1959, 628, 117.the CF,I group, whereas the corresponding signal ofRFI appears at 59 p.p.m.I t has not been possible to determine the structure of(C) by X-ray crystallography because of the difficultyto obtain a suitable crystal.On the basis of the aboveexperiments it is reasonable to assume a charge-transfercomplex between an iminium iodide and RFI. Theimportance of the anion (iodide) and of the iminiumstructure are clearly demonstrated since neither theiminium perchlorate corresponding to (B) nor th1977 1367ammonium iodide MeEt,N+I- show any sign of com-plexation with RpI.An excess of enamine decreases the yield of complexwith C,FI3I without irradiation.2-perfluorohexyl-N-methyl-4-piperidone is only 20%.However the yield ofAttempts to introduce a peduoroalkyl chain into( 6 ) , C g F 1 3 1 4- MeCH=CEt*N 3 4. + C6F13MeCH*COEt( 4 f ) ( C 1c 6 F1 3( 4 g )(C) , which disappears completely when a three-foldexcess of enamine is used.Formation of (C) is shownto be reversible as follows. (i) If (C), in suspension ini , C z F g l , h 3P hC H=CMe*N __c___) CF3-CF=CPh6COMeii, H 3 O *( 6 ) ( 2 5 ' l o ) 3pentane, is mixed with the same enamine as used for itssynthesis, it disappears giving the iminium iodide (B)and enamine (3). (ii) If (C) is mixed with an enamine3-dimethylaminopropanal have not been successful.Likewise conjugated dienamines give only small yieldsof condensation products.U.V. irradiation is necessary to effect the reactionbetween but-l-enylpyrrolidine and perfluorohexyl iodide.Hydrolysis affords a cis-trans-mixture (7 : 9) of isomericketones (7) in 50% geld. Traces of the saturatedaldehyde (8) were also isolated (2%).A difference inreactivity between 2-methylpropenylpyrrolidine and itsstraight-chain isomer in condensations with CC1, hasother than the one used for its formation, the two been reported. The proportion of the saturatedpossible a-perfluoroalkyl ketones are produced after aldehyde (8) can be increased to 15% if no amine is usedhydrolysis. during irradiation (the total yield is then only 33%).The intermediate enamine (3h) does not yield an enamino- Extension of the Reaction to Other Urtsaturated Nitrogeni, c 6f13'Ii i , H 3 0 +R C H=C (OE t 1 N Me;! C 5F1fC F=C R * C O 2 E t 3. C5 F1l 0 CF=CR CO 4 N Me2( 1 3 ) a ; R = Hb; R = MeCzF5-MeCH.CO.NEt 2 (18 ) ( 6O0lO)Compounds.-An attempted extension of the abovereaction to deactivated enamines such as enamino-ketones (R = COR') or enamines bearing a p-phenylsubstituent (R = Ph) has met with only little success.Condensation of a-methylstyrylpyrrolidine with per-fluoroethyl iodide requires U.V.light, and hydrolysisyields only 25% of the unsaturated ketone (6).(N-Met h ylt e t rahydro-4-p yridyl) pyrrolidine reactsketone after hydrolysis, such as observed with cycliccompoundss or when the p-carbon bears a hydrogenatom.gThe heterocyclic amine (9) condenses easily withCF31. The reaction affords, as expected, a mixture ofenamines (10) and (11) in the ratio 2 : 1, identified afterreduction of the double bonds (NaBH,). The resultingamines were obtained in the same ratio. When CF31J. C . Blazejewski, D. Cantacuzhe, and C .Wakselman, 9 M. Leblanc, G. Santini, and J. C. Riess, Tetrahedron Letters,Tetrahedron Letters, 1974, 2056. 1975, 41511368 J.C.S. Perkin Iwas used in excess, compound (12) was isolated; it wasalso reduced (NaBH,) for identification.The a-alkoxy-enamine (13a) reacts with C6F131 underirradiation: here also an amine was used to trap HI.After hydrolysis the a@-unsaturated ester (14a) wasobtained in 40?& yield (without U.V. irradiation the yieldchain-mechanism in the cases where irradiation isnecessary cannot be excluded.In summary, two conditions are necessary for thereactions described here to take place without U.V. orradical initiator: the lone pair on the nitrogen must beavailable to give a charge-transfer complex, and thei n i t i a t i o n @= + R F I - O L J + RF' + I -was only 7%).With compound (13b) the condensationwas easily performed at room temperature withoutirradiation. Hydrolysis yielded a mixture of aP-unsaturated ester and amide [(14b) and (15b), re-spectively lo] in the ratio 3 : 1. Attempts to avoid lossof HF were not successful.Condensation of the ynamine (16) with C2F51 under U.V.light for 2 h produced, after hydrolysis, the amide (18) in60% yield. The thermally initiated addition of CF31 todouble bond must be rich enough in electrons to add theRF* radical.The condensation of pyrroles with perfluoroalkyliodides does not take place under the conditionsdescribed for the enamines. As with arene derivatives l2or with pyridine,l3 condensation is achieved by heatingthe mixture.The reaction temperature depends on theperfluoroalkyl iodide used. Yields are 30--4570. Asusually observed,14 condensations with N-methylpyrrole( 1 9 ) R = Me, RF = C 2 F 5 ; T190°C (300i0)(20) R = Me, R F = C6F13; T155'C (45'10)( 2 1 ) R = CHzPh, RF = c6F13; T 1 6 0 ' C ( 3 O o / o )+ RFI & QRFR RNN-bistrifluoromethylethynylamine [ (CF,),N-C-CH]has been reported l1 (215 "C; 22 h; CF31 in excess).Surprisingly, the intermediate (17) does not display theiminium structure (17b) as evidenced by n.m.r. spectro-scopy, The enamine (17a) can even be distilled withoutalteration. In the case of ynamines the need ofirradiation for the reaction to take place can be explainedby the fact that the nitrogen lone pair is not availableenough to give a charge-transfer complex and thus toinduce rupture of the RF-I bond.However, when asmall amount of cyclohexenylpyrrolidine is added to thesolution containing the ynamine and RFI, the reactionproceeds and the amide (18) is obtained in 10% yieldafter hydrolysis. In this case the enamine has initiatedthe formation of the perfluoroalkyl radical, which thenreacts with the electron-rich ynamine in a normal shortchain reaction.Of the two mechanisms suggested in the Introductionthe chain mechanism (Scheme 2) appears more likely;indeed its existence has been proved in the case ofynamines. It has not been possible, however, to initiatethe condensation of but-l-enylpyrrolidine with cyclo-hexenylpyrrolidine ; therefore competition of the coup-ling of the two radicals RF* and (A) (Scheme 1) with thelo P. Deslongchamps, S.Dub4, C. Lebreux, D. Patterson, andR. Taillefer, Canad. J. Chem., 1975,55, 2791.11 J. Freear and A. E. Tipping, J . Chem. Soc. ( C ) , 1968, 1096.12 M. Birchall, G. Irvin, and R. A. Boysson, J . C . S . Perkin IT,1975, 435.1s (a) L. M. Yagupolski, A. G. Galushko, and M. A. Rzhavin-skaya, Zhur. obshchei Khim., 1968, 38, 668 (Chem. Abs., 1968, 69,59064b); (b) L. M. Yagupolski, A. G. Galusko, and V. I. Troit-skaya, ibid., p. 1736 (Chem. Abs., 1969, 70, 5213b).afford specific substitution at the 2-position. Productswere identified by n.m.r. (250 MHz spectrometer).When heated at 160 "C with C,F,,I, pyrrole onlyproduces tar.We hoped to be able to protect the NHfunction with a benzyl group: in this case the expectedN-benzyl-2-perfluoroalkylpyrrole (21) was obtained in30% yield. However attempts to remove the benzylgroup with sodium in liquid ammonia l5 or by catalyticreduction l6 were not successful.EXPERIMENTALlH N.m.r. spectra were recorded with a Hitachi-Perkin-Elmer R24 spectrometer (Me,Si as internal standard),1°F N.m.r. spectra were run a t 56.4 MHz with a JEOL60 HL instrument (positive values to high field of internalCFC1,). Spectra at 250 MHz were obtained with aCAMECA instrument. 1.r. spectra were measured with aPerltin-Elmer 457 spectrometer, and U.V. spectra with aVarian-Techtron 635 instrument. U .v. irra.diation wasperformed with a high-pressure mercury lamp (TQ Hanau)in a silica vessel.Spinning-band distillations were carriedout with a Nester Faust NFT 51 column.Perfluoroalkyl iodides (RF = C,F,, C6FI3, or CBF1,) werea gift from PCUK. CF,I and C,F,I are commercialproducts (PCR, U.S.A.). All unsaturated amines werecarefully distilled under nitrogen before use.a-Perfluoroalkyl Ketones and A 1dehydes.-Procedure A :l4 (a) H. J. Anderson and H. Nagy, Canad. J. Chem., 1972,1961 ; (b) T. S . Croft and J. J. Brady, J. Heterocyclic Chem., 1975,845.l5 M. Julia, P. Manoury, and I. Igolen, Compt. rend., 1960, 251,394.l6 J . S. Buck and R. Baltzgly, J . Amer. Chem. Soc., 1941, 68,19641977 13692-(~er$uoroethyZ)cycZohexanone (4d). N-Cyclohex- l-enyl-pyrrolidine (9 g, 0.06 mol) was dissolved in pentane (150 ml)with N-ethyldi-isopropylamine (EDPA) (7.8 g, 0.06 mol).Perfluoroethyl iodide (7.4 g, 0.03 mol) was added to thesolution.A solid C0,-acetone condenser was used to avoidevaporation of the iodide. A precipitate of EDPA hydro-iodide was formed instantaneously. After 3 h the precipi-tate was filtered off and the solution evaporated. [If theenamine (3d) is distilled, loss of H F is observed.] The crudeliquid was hydrolysed with 40% H,SO, (6 ml: the minimumquantity to give an acidic medium). The mixture is stirredfor 3 h and extracted with ether. The ether layer wasneutralized with aqueous sodium hydrogen carbonate,washed with water, and dried (MgSO,). Distillation of thecrude liquid afforded a mixture (3.4 g) shown by 19F n.m.r.to consist of 2-(~erfEuoroethyZ)cycZohexanone (4d) and thecorresponding unsaturated ketone (5d) in the ratio 93 : 7.The ketone (4d) was purified by spinning-band distillation ;b.p.90-92' a t 20 mmHg (3.1 g, 48%); v,,,. (CCl,) 1 725-1738 cm-l; 19F n.m.r. (CDC1,) 83.3 (s) and 118.7 p.p,m.44.15. C,H,F,O requires C, 44.45; H, 4.2; F, 43.95%).Procedure B : 2-(per$uorohexyZ)butyruZdehyde (8). (a) N-But-l-enylpyrrolidine (5 g, 0.04 mol) was dissolved inpentane (250 ml) containing EDPA (5.2 g, 0.04 mol).Perfluorohexyl iodide (9 g, 0.02 mol) was added. Irradi-ation was carried out a t 0-10 "C for 3 h. The precipitateof EDPA hydroiodide was filtered off and the solutionevaporated. Hydrolysis of the liquid with 40% H,SO,(5 ml) and work-up as above produced after distillation(b.p.30-35" a t 0.5 mmHg) 3.9 g (48%) of a mixtureshown by lH n.m.r. t o consist of the isomeric aldehydes (7)and traces (2%) of the saturated aldehyde (8). Thealdehydes (7) and (8) were purified by g.1.c. on FFAP;2-ethyZ~er$uoro-oct-2-enuZ (7) (c : t 35 : 45) showed vmx.(CC1,) 1658-1 690 cm-l; T (CCl,) 8.93 (t), 7.55 (m), 0.1,and -0.1; 19F n.m.r. 81 p.p.m. (CF,) (Found: C, 32.35;H, 1.55; F, 61.0. CloH,F120 requires C, 32.45; H, 1.65;F, 6 1.6 yo). 2- (Per$uorohexyZ) butyrddehyde (8) had vmaX.(CC1,) 1 728-1 735 cm-l; T (CCl,) 9.00 (t), 8.08 (q), 7.1, and0.48 (m); 19F n.m.r. 80.5 p.p.m. (CF,) (Found: C, 30.8;H, 1.75; F, 63.2. CloH7Fl,0 requires C, 30.8; H, 1.8;F, 63.1%).( b ) Irradiation a t 0-10 'C of N-but-l-enylpyrrolidine(0.04 mol), in pentane (250 ml), with perfluorohexyl iodide(0.02 mol) produced after the usual work-up and distillation(b.p.30-35" a t 0.5 mmHg) a mixture shown by 1H n.m.r.to consist of the aldehydes (7) and (8) in the ratio 60 : 40(2.6 g ; total yield 33%).2-TrzfEuorornethylpentan-3-one (4a). Condensations withtrifluoromethyl iodide do not require the use of a tertiaryamine. The best yields are obtained when a two-foldexcess of enamine is used. Thus N-( l-ethylprop- l-eny1)-pyrrolidine (8.4 g, 0.06 mol) and trifluoromethyl iodide(6 g, 0.03 mol) were dissolved in pentane (150 ml). Pro-cedure A was followed. Distillation (spinning-band column)yielded 2-tra$uoromethylpentan-3-one (2 g, 45%), b.p. 68-70' at 134 mmHg; v,,, (CCl,) 1 726-1 735 cm-l; T (CDCl,)8.95 (t), 8.69 (d), 7.42 (q), and 6.62 (m); 19F n.m.r.69.5p.p.m. (JHF 8.5 Hz) (Found: C, 46.8; H, 5.8; F, 36.35.C,H,F,O requires C, 46.75; H, 5.9; F, 36.95%).The same procedureas for (4a) gave 2-trifEuoromethyZcyclohexunone, purified fromcyclohexanone by spinning-band distillation (yield 45%) ;b.p. 90-92" a t 30 mmHg; vmX. (CCl,) 1735 cm-1; l9F( I F F 276.7, J H F 15.2 Hz) (Found: C, 44.4; H, 4.2; F,2- Trz$uoromethyZcycZohexanone (4b).n.m.r. 69.5 p.p.m. (JHF 8.2 Hz) (Found: C, 50.6; H, 5.4;F, 34.0. C7H9F,0 requires C, 50.6; H, 5.45; F, 34.3%).The intermediate enamine, N- (6-trz$uoronzethyZcycZohex-1-enyZ)pyrroZzdine (3b), can be distilled without loss of H Fbut cannot be separated from N-cyclohex- l-enylpyrrolidine ;(3b) is obtained pure by the TiC1, method of Weingarten ; l7condensation is carried out a t room temperature; b.p.85-90' at 30 mmHg; v,,,.(liquid) 1 645 cm-l (C=C str.);T (CDCl,) 5.37 (C=CH); l9F n.m.r. 68 p.p.m. (CF,, d,J 7.9 Hz).2-Per$uoroethylpentan-3-one (4c). Procedure A : afirst distillation yielded a mixture shown by l9F n.m.r.to consist of 2-perfluoroethyZpentan-3-one (4c) and thecorresponding unsaturated ketone (5c) in the ratio 95 : 5.The ketone (4c) was purified by spinning-band distillation(yield 48%); b.p. 53-55' a t 55 mmHg; vmx. (CC1,)1725-1 735 cm-l; T (CDCl,) 8.95 (t), 8.69 (d), 7.44 (q),and 6.62 (m); lSF n.m.r. 83.7 (s) and 119.5 p.p.m. (JFp 279,JHF 19.4-10.2 Hz) (Found: C, 44.5; H, 4.0; F, 43.8.C,H,F,O requires C, 44.45; H, 4.2; F, 43.95%).2- Per$uoropropylpentan-3-one (4e).Procedure A : dis-tillation of the products obtained after hydrolysis yieldeda mixture shown by 19F n.m.r. to consist of 2-perfluoro-propyZpentan-3-one (4e) and the corresponding unsaturatedketone (5e) (15%). The ketone (4e) was purified byspinning-band distillation (yield 43%) ; b.p. 76-78" at80 mmHg; vmax. (CCl,) 1 725-1 735 cm-l; T (CCl,) 8.93 (t),8.63 (d), 7.6 (q), and 6.6 (m) ; l9F n.m.r. 81.5 (t, JFF 9.8 Hz),114 (m), and 124 p.p.m. (m) (Found: C, 37.8; H, 3.5; F,52.0. C,H,F,O requires C, 37.8; H, 3.55; F, 52.3%).2-(PerfEuorohexyZ)pentan-3-one (4f). Distillation of theproducts obtained after hydrolysis (procedure A) gave amixture shown by lH n.m.r.to consist of 2-(per$uorohexyZ)-pentan-3-one (4f) and the unsaturated ketone (5f) in theratio 93 : 7. The ketone (4f) was purified by spinning banddistillation (yield 63%); b.p. 86-87' a t 18 mmHg; vmaX.1720-1 735 cm-l; T (CDCl,) 8.95 (t), 8.68 (d), 7.42 (q),and 6.62 (m); l9F n.m.r. 81.6 (CF,), 115.2, 121.2, 123.3,and 126.6p.p.m. (CF,) (Found: C, 32.65; H, 2.3; F, 61.0.CllH9F1,0 requires C, 32.7; H, 2.25; F, 61.1%).2-(Per$uorohexyZ)cycZohexunone (4g). Procedure A : be-cause of the complexity of the n.m.r. signals, it is notpossible t o give a value for the percentage of the un-saturated ketone (5g), which was characterized by its i.r.C=C band a t 1 680 cm-l. 2-(Per$uorohexyZ)cycZohexunone(4g) was purified by spinning-band distillation (yield 63%) ;b.p.71-73' at 0.4 mmHg; vmaX. (CCl,) 1 725-1 735 cm-1;19F n.m.r. (CCl,) 80.4 (CF,), 111.6, 118.2, 120.7, and 124.9p.p.m. (CF,) (Found: C, 34.6; H,2.35; F,59.1. Cl,H9Fl,0requires C, 34.65; H, 2.2; F, 59.35%).l-MethyZ-3-(~erfluorohexyZ)-4-Pi~eridone. Procedure A : afirst distillation of the crude liquid yielded a mixture ofl-methyl-3-perfluorohexyl-4-piperidone and the correspond-ing unsaturated ketone (characterized by its i.r. C=C banda t 1 680 cm-l) (total yield 20%). However it was notpossible to purify the saturated ketone which decomposedduring spinning-band distillation ; the mixture had b.p.85-90' at 1 mmHg; vmx. (CCl,) 1 725-1 680 cm-l; 19Fn.m.r. (CCl,) 81 (CF,), 114, 119, and 123 p.p.m. (CF,).2,2-DimethyZ~erfluoro-octanaZ (2).Condensation of per-fluorohexyl iodide with N-( 2-methylprop- l-eny1)pyrrolidinedoes not require the use of a tertiary amine. A two-foldexcess of enamine is used. Thus the enamine (7.5 g,l7 W. A. White and H. Weingarten, J . Org. Chem., 1967, 32,2131370 J.C.S. Perkin I0.06 mol) and perfluorohexyl iodide (13.4 g, 0.03 mol) weredissolved in pentane (150 ml). A precipitate appeared.After 3 h pentane was evaporated off. The remainingsolid-liquid mixture was shown by 1H n.m.r. to consist ofthe iminium iodide (l), T (CDCl,) 0.25 (CH=N) and 6.6(N-CH,) ; 19F n.m.r. 81 p.p.m. (CF,) ; which is air sensitive.The mixture was hydrolysed and after usual work-up anddistillation gave the aldehyde (2) (7 g, 60%); b.p. 65-67' at15 mmHg; vmx.2 700-1 715 cm-l; T (CCl,) 8.67 and 0.5;19F n.m.r. 80.1 (CF,), 117, 119, 122.8, and 126.6 p.p.m.(CF,) (Found: C, 30.9; H, 1.7; F, 63.15. C,,H,F,,Orequires C, 30.8; H, 1.75; F, 63.2%).4,5,5,5-Tetrafluoro-3-phenylpent-3-en-2-one (6) .-N-(a-Methylstyry1)pyrrolidine (1 1.2 g, 0.06 mol) was mixed withpentafluoroethyl iodide (7.4 g, 0.03 mol) and EDPA (7.8 g,0.06 mol) in pentane (250 ml). Procedure B was followed.After the usual work-up, and spinning-band distillation,the pentenone (6) was obtained (1.7 g, 25%); b.p. 90-91"at 20 mmHg; vmX. (CCl,) 1722-1 700 cni-l; T (CCl,) 7.7(d, J 2 Hz); 19F n.m.r. 53.5 (d, JPF 9.15 Hz) and 100 p.p.m.(m) (Found: C, 56.5; H, 3.7; F, 32.25. CllH80 requiresC, 56.9; H, 3.45; F, 32.75%).Unsaturated Ketones (5).-The ketone (4) (0.015 mol) wasstirred with aqueous 15% sodium hydroxide (2 ml) [2.5 hfor (4c, d, and f)] or with aqueous 40% sodium hydroxide[0.5 h for (4e)l.Completion of the reaction was deter-mined by n.m.r. so as not to leave the ketone (4) too longin the basic medium. The aqueous phase was thenextracted with ether; the ether layer was neutralised with10% hydrochloric acid, washed with water, and dried(MgSO,). The ketones (5) were purified by spinning-banddistillation (yield 60%). 2-(Perfluoroethylidene)pentan-3-one (5c) had b.p. 40" at 40 mmHg; v,,,. 1725-1 700-1 675 cm-1; Amx. (cyclohexane) 216 nm ( E 6 030); T (CCl,)8.9 (t), 8.07 (9, J 2.3 Hz), and 7.34; 19F n.m.r. 68.4 (d of d,J 7 and 2.5 Hz) and 122 p.p.m.(only one isomer) (Found:C, 45.25; H, 4.2; F, 40.8. C,H,F,O requires C, 45.65;H, 4.4; F, 41.25%). 2-(Perfluoroethylidene)cyclohexanone(5d) (c + t) had b.p. 60" at 15 mmHg; v,,,. 1725-1700-1 680 cm-1; 19F n.m.r. (CDCl,) 67.4-68.7 (CF,, JETF 6.3 and8.5, JFH 0.7 Hz), 125.3, and 129.9 p.p.m. (CF) (Found: C,48.95; H, 4.19; F, 38.45. C8H8F,0 requires C, 49.0; H,4.1 ; F, 38.75%). 2-(Per$uoro~ro~ylidene)~entan-3-one (5e)had b.p. 35" a t 30 mmHg; v,,, (CC1,) 1 722-1 700-1 670cm-1; A,,,. (cyclohexane) 218 nm (E 6 072); T (CCl,) 8.9 (t),8.09 (9, J 2.3 Hz), and 7.3 (m); 1BFn.m.r. 83 and 84 (d of t,J1 2.3, Jz 8.5; J'l 2.3, J'z 7 Hz), 116 (m), and 117 p.p.m.(two isomers in 90: 10 ratio) (Fouhd: C, 41.25; H, 3.4;F, 47.85. C8H8FeO requires C, 41.05; H, 3.45; F, 48.7%).2-(Per$uorohexyZidene)pentan-3-one (5f) had b.p.77-80"a t 30 mmHg; vmx. (CCl,) 1722-1 700-1 670 cm-l; A,,,.(cyclohexane) 218 nm (E 6 100); T (CCl,) 8.9 (t), 8.1 (9,J 2.3 Hz), and 2.66; 19F n.m.r. 81.5 p.p.m. (CF,) (Found:C, 36.1; H, 2.25; F, 61.45. C11H8Fl,0 requires C, 35.9;H, 2.2; F, 61.9%).Heterocyclic Elaamines (lo)-( 12) .-(a) A mixture ofA4Wa)- and A8- 1-methyloctahydroquinoline (9) (3.4 g,0.02 mol) was added to a solution of trifluoromethyl iodide(4 g, 0.02 mol) in pentane (150 ml). After 3 h the pre-cipitate was filtered off and pentane was removed underreduced pressure. A first distillation yielded a mixture(3 g) shown by g.1.c. to consist of unchanged enamine (9)(50y0), 35% of (lo), and 15% of (11). l-Methyl-4a-tri-fluoromethyl-A8-octahydroquinoline ( 10) was purified byD. A.Evans, J . Amer. Chem. SOC., 1970, 92, 7593.t.1.c. on silica gel 60 FP (benzene as eluant); vmx. (liquid)1 643 cm-l; T (CDCl,) 7.6 and 5.2 (C=CH); 19F n.m.r.67.1 p.p.m. (s); m/e 219 (M+), 204, 190, and 189. Com-pound (11) displays a lgF n.m.r. signal a t 66.3 p.p.m. (d,J 8.5 Hz) ; it was not purified.(b) The distilled mixture (3 g) was introduced into a flaskwith tetrahydrofuran (250 ml) and sodium borohydride(3 g). Glacial acetic acid (75 ml) was added dropwise.The mixture was refluxed for 2 h. Tetrahydrofuran wasremoved under reduced pressure, and the residual liquidwas neutralized with 10% sodium hydroxide and extractedwith ether; the ether layer was washed with water, dried(MgSO,), and evaporated.Distillation of the crudeproduct (2.9 g) (b.p. 68-75' at 1 mmHg) gave a mixture(2.7 g) shown by g.1.c. to consist of l-methyldecahydro-quinoline (50 yo), l-methyl-4a-trz$uo~omethyldecahydroquino-line (35%), and l-methyl-8-trifluoromethyl decahydro-quinoline (15%). The 4a-trifluoromethyl derivative waspurified by preparative g.1.c. on an SE 30 column (yield0.7g, 15%); .c(CDCl,) 7.82 (N-CH,); lgFn.m.r. 588p.p.m.(s) (Found: C, 60.1; H, 8.35; F, 25.15. CllH18F,Nrequires C, 59.7; H, 8.2; F, 25.75%). It was not possibleto purify the 8-trifluoromethyl derivative by g.1.c. : 10%of the 4a-isomer is always present. The 19F n.m.r. spectrumof the former displays a signal a t 64.6 p.p.m. (d, J 9.5 Hz).Its analytical figures (with 10% of the 4a-isomer) are correct(Found: C, 59.1; H, 8.55; F, 24.75%).(c) The enamine (9) (5.5 g, 0.036 mol) was dissolved inpentane with an excess of trifluoromethyl iodide (9 g,0.046 mol).Usual work-up and distillation afforded amixture (6 g) shown by g.1.c. and 19F n.m.r. to consist ofthe enamines (9)-(12); ratio (10) : (11) : (12) 6 : 2 : 1. The19F n. m. r . spectrum of 1 -methyl-4a, 8-bistrifluoromethyl-A8-octahydroquinoline (12) displays signals a t 62.5 and68.4 p.p.m. Compound (12) was identified after reductionof the distilled mixture (6 g) by sodium borohydride asabove. 1 -MethyZ-4a, 8-bistri$uoromethyldecahydroquinolinewas purified by g.1.c. on an SE 30 column (yield 0.3 g);T (CDC1,) 7.72 (N-CH,); lgF n.m.r. 60.4 (quint., JHF =JFF = 11 Hz) and 61.7 p.p.m.(q, J F ~ 11 Hz). Identific-ation was performed after fluorine spin-spin decoupling(Found: C, 50.15; H, 5.85; F, 38.85. C,,H1,F,N requiresC, 49.8; H, 5.95; F, 39.4%).a-A lkoxy-emmines.-(a) Procedure B : from l-ethoxy-NN-dimethylvinylamine (13a) (2.3 g, 0.02 mol), perfluoro-hexyl iodide (4.5 g, 0.01 mol), and EDPA (2.6 g, 0.02 mol),ethyl 2H-dodecu$uoro-oct-2-enoate (14a) (1.5 g, 40%) wasobtained after distillation; b.p. 73-75' a t 18 mmHg;v,,,. (CC1,) 1702-1 740-1 750 cm-l; T (CC1,) 4.1 ( J H ~30 Hz), 5.75 (q), and 8.7 (t); 19F n.m.r. 81 p.p.m. (CF,)(Found: C, 31.25; H, 1.55; F, 58.75. C1,H6Fl,0, requiresC, 31.1; H, 1.55; F, 59.05y0).(b) Procedure A : from 1-ethoxy-NN-dimethylprop- 1-enylamine (13b) (7.8 g, 0.06 mol), perfluorohexyl iodide(13.5 g, 0.03 mol), and EDPA (7.8 g, 0.06 mol), 3.6 g (30%)of ethyl dodecafluoro-2-methyloct-2-enoate (14b) (3.6 g, 30%)and dodecafluoro-2,NN-trimethyloct-2-enamide (1 5b) (1.2 g,10%) were obtained after the usual work-up and distil-lation: (14b), b.p.53-55' at 2 mmHg; vmax. (CCl,) l 725brcm-1; T (CC1,) 5.73 (q), 8.0 (m), and 8.7 (t); 19F n.m.r.82.5 p.p.m. (CF,) (Found: C, 32.85; H, 2.15; F, 56.35.CllH8FlzOz requires C, 33.0; H, 2.0; F, 56.9%); (15b),b.p. 70-72' at 2 mmHg; v,,,. 1 662 cm-l; 7 (CCl,) 7.92 (m)19 H. Bredereck, F. Eggenberger, and H. P. Beyerlin, Chem.Ber., 1964, 97, 30811977 1371and 7 (m); 19F n.m.r. 82 p.p.m. (CF,) (Found: C, 33.25;H, 2.25; F, 56.75. C11HgF12N0 requires C, 33.1; H, 2.25;F, 57.1%).Ynamine.-(a) 1-Diethylaminopropyne (16) (4.8 g, 0.04mol) was dissolved in pentane (250 ml) with perfluoroethyliodide (10 g, 0.04 mol).Irradiation was carried out for 3 h.A small amount of viscous precipitate was removed and thesolution was evaporated. The remaining liquid l-diethyl-aminopentafluoro- l-iodo-2-methylbut-l-ene (17a) (13 g)showed T 8.15 (s, CH,), 0.02 (t), and 7.9 (m) (NEt); lgFn.m.r. 83.3 (s) and 110 (s) p.p.m. The chemical shift forNCH, is as expected: no trace of an iminium structure wasdetected. Compound (17a) can be distilled (b.p. 95-100"a t 15 mmHg); the product (11 g) displayed the samen.m.r. spectra as above, with an extra NCH, signal at6 7.28 (m) (10%) ; this chemical shift does not correspondto an iminium structure. The crude mixture (13 g) wascooled (ice-bath) and hydrolysed with 15% sulphuric acid;the aqueous phase was extracted with ether.The etherlayers were washed with sodium hydrogen sulphite solution,neutralized with sodium hydrogen carbonate, then washedwith water, dried (MgSO,) , and evaporated. Distillationgave NN-diethyl-2H-pentafluoro-2-methylbutyramide ( 18) (6 g,60%), b.p. 110' a t 15 mmHg; vmX. (CCl,) 1655br cm-l;T (CC1,) 8.72 (d o f t ) , 8.6 (d), and 6.7 (m); l9F n.m.r. 83.4(s, CF,) and 119 p.p.m. (CF,, JHF 4.9 Hz) (Found: C, 43.6;H, 5.6; F, 38.05. CgHl,F,NO requires C, 43.75; H, 5.7;F, 38.45%).When the ynamine and perfluoroethyl iodide were mixedin pentane and left without irradiation, an abundantviscous product was formed but no condensation to give(17) appeared to occur.( b ) l-Diethylaminopropyne (6 g, 0.06 mol) was mixedwith perfluoroethyl iodide (8 g, 0.03 mol) in pentanesolution. N- (Cyclohex- l-eny1)pyrrolidine (40 mg) wasadded.Formation of compound (17) was determined bylgF n.m.r. analysis; a viscous product also appeared whichdid not contain the expected (17). After 1.5 h the solutionwas evaporated and the products were hydrolysed as above.Distillation gave a mixture (0.7 g, 10%) of the amide (18)and the corresponding aP-unsaturated amide. A parallelexperiment was carried out without added enamine :in this case no (17) appeared in the solution; only theviscous product was formed.Methylpyrrole (2.5 g, 0.03 mol) was introduced with per-fluoroethyl iodide (4 g, 0.015 mol) and EDPA (3.9 g, 0.03mol) into an autoclave.The mixture was heated at 190 "Cfor 3 h. Cooling, filtration, and column chromatography ofthe remaining liquid on silica gel 60 (pentane as an eluant)gave l-methyl-2-perfluoroethyl~y~role (1 9) in the first fraction(0.9 g, 30%); t (CCl,) (250 MHz) 6.28 (CH,), and 3.4, 3.56,and 3.99 (1 H) (J1 3.75, J , 2.25, J , 1.25 Hz); 19F n.m.r. 83.4(t, J 2.8 Hz) and 106 p.p.m. (Found: C, 42.55; H, 3.1;F, 47.35. C,H,F,N requires C, 42.2; H, 3.05; F, 47.7%).l-Methyl-2-perfluorohexylPyrrole (20). The same pro-cedure as above was used: the mixture was heated a tPyrroles.-l-Methyl-2-perfluoroethyl~yrrole (1 9). N-155 "C. N-Methylpyrrole (2.5 g), perfluorohexyl iodide(6.7 g), and EDPA (3.9 g) gave the 2-perfluorohexylpyrrole(20) (2.7 g, 45%); b.p.50-53" at 0.5 mmHg; t (CC1,)(250 MHz) 6.32 (CH,), and 3.3, 3.45, and 3.9 (1 H) (J1 3.75,J 2 2.25, J , 1.3 Hz); 19F n.m.r. 80.5 p.p.m. (CF,) (Found:C, 32.85; H, 1.7; F, 61.65. Cl,H8Fl,N requires C, 33.1;H, 1.5; F, 61.9'70).A mixture of N-benzylpyrrole (3.2 g, 0.02 mol), perfluorohexyl iodide (4.5 g,0.01 mol), and EDPA (2.6 g, 0.02 mol) was heated at 155 "Cfor 3 h. The usual work-up gave the 2-perfluorohexyl-pyrrole (21) (1.4 g ) ; m.p. 36-38"; T (CCl,) 4.95 (CH2Ph),and 3, 3.45, and 3.9; l9F n.m.r. 82.2 p.p.m. (CF,) (Found:C, 42.6; H, 2.25; F, 51.1. Cl,Hl,Fl,N requires C, 42.95;H, 2.1; F, 51.95%).Charge-transfer Complex between the Iminium Iodide (B)and Perfluoro-octyl Iodide.-Formation.N-( Cyclohex- 1-eny1)pyrrolidine (4.5 g, 0.03 mol) was dissolved in pentane(150 ml) with perfluoro-octyl iodide (16.9 g, 0.03 mol).After 2 h the precipitate was carefully filtered off underargon and dried a t atmospheric pressure in a desiccatorfilled with argon and containing P20, to give 9.5 g of solidcomplex; A,,,. (dioxan) 292 nm, Am,. (CHC1,) 286 nm(Found: C, 26.3; H, 2.2; F, 38.55; I, 29.95; N, 1.55.C18H18F1712 requires C, 26.2; H, 2.2; F, 39.15; I, 30.7;N, 1.7%). The complex obtained from cyclohexenyl-morpholine displays U.V. absorption a t 268 nm (dioxan).Heated at 110 "C and 15 mmHg, the precipitate(9.5 g) decomposed to give perfluoro-octyl iodide (4.2 g).Hydrolysis of the remaining iminium iodide (B) in basicmedium yielded cyclohexanone (0.9 g) and perfluoro-octyliodide (0.8 g). Hydrolysis of the precipitate (9.5 g) in anacidic medium gives perfluoro-octyl iodide (5 g) (from anextraction in acidic medium) and cyclohexanone (0.9 g)(from an extraction in basic medium).Exchange. N-(Cyclohex- l-eny1)pyrrolidine (4.5 g, 0.03mol) was dissolved in pentane (150 ml) with perfluorohexyliodide (13 g, 0.03 mol). The precipitate was filtered offafter 2 h, dried as above [6.8 g of (C) were obtained], andintroduced into a pentane solution containing N-( l-ethyl-prop- l-eny1)pyrrolidine (2 g) . After 4 h the precipitatewas filtered off and the solution evaporated. The liquidobtained was hydrolysed as usual. Distillation gave twoketones: b.p. 55 "C a t 15 mmHg, 0.4 g [ketone (4f)l; b.p.80 "C at 15 mmHg, 0.9 g [ketone (4g)l.Independent synthesis. The iminium iodide (B) wassynthesized by addition of a solution of hydrogen iodidein pentane to N-(cyclohex- l-eny1)pyrrolidine in the samesolvent. The iminium salt (5.6 g, 0.02 mol) was washedseveral times with pentane and finally added to a solutionof perfluoro-2-octyl iodide (12.5 g, 0.023 mol) in pentane.After 3 h the new precipitate was filtered off: its l9F n.m.r.spectrum displayed the same signals as (C) and its U.V.spectrum showed the same absorption maximum.We thank the D.G.R.S.T. for financial support.N-Benzyl-2-perfluorohexylfiyrrole (21).Stability.[6/1939 Received, 18th October, 1976
ISSN:1472-7781
DOI:10.1039/P19770001365
出版商:RSC
年代:1977
数据来源: RSC