SODIUM 2,6-I)IMETHYLPHENOXIDE WITH PERCHLORYL FLUORIDE
Oct. 20, 1961 [CONTRIBUTION FROM
THE
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ORGANICCHEMICAL RESEARCH SECTION, LEDERLE LABORATORIES, A DIVISIONOF AMERICAN CYANAMID Co., PEARLRIVER,N. Y . ]
Reaction of Sodium 2,6-Dimethylphenoxide with an Ambident Electrophile : Medium Effect and Mechanism BY ANDREWS. KENDEAND PAULMACGREGOR RECEIVED APRIL 28, 1961 Nucleophilic displacement b y sodium 2,6-dimethylphenoxide upon perchloryl fluoride in a hydrocarbon or dioxane medium (Va). In ethanol or dimethylformamide there releads t o the dimer (IVa) of 6-fluoro-2,6-dimethyl-2,4-cyclohexadienone (Vb). Under all reaction conditions consults instead the dimer (IVb) of 6-hydroxy-2,6-dimethyl-2,4-cyclohexadienone siderable oxidation of the phenoxide to quinonoid products is observed, while with the neutral phenol in dimethylformamide the p-chlorophenol is a n additional product. The pronounced medium effect on the formation of fluorodienone Ya vs. hydroxydienorie Vb is discussed in terms of current hypotheses regarding the alkylation of ambient nucleophiles.
The selective formation of a carbon-fluorine sharp maxima a t 5.74 and 5.55 p in the infrared, bond by reaction of a mesomeric carbanion with a n ultraviolet absorption peak at 241 mp (log E perchloryl fluoride has been ingeniously exploited 3.80)’ and FI9 nuclear magnetic resonance conin the recent literature.’ Although. the classical sisting of two 1:3:3:1 quartets each having J studies of Claisen and his associates2 have shown 24 f 1 C . P . S . ~ These properties suggested the that phenoxides can undergo ortho C-alkylation by presence of gross structures I11 or IVa, either of alkyl halides, the possibility of achieving analogous which could arise from an initially-formed 6C-fluorination by the use of perchloryl fluoride fluoro-2,6-dimethyl-2,4-cyclohexadienone (Va) by does not appear to have received specific scrutiny. Diels-Alder autodimerization. Although the obIn the light of fundamental studies by Curtin,4 served proton magnetic resonance did not permit Kornblum5 and their co-workers upon the Claisen decision between I11 and IVa, a choice could be ortho-alkylation of “ambident” phenoxide anions, made in favor of IVa on the basis that the dimers we have undertaken to examine the action of of 6-hydroxy-2,6 - dimethyl - 2,4 - cyclohexadienone perchloryl fluoride on one such anion in particular (Vb)7 and of 2,6,6-trimethyl-2,4-cyclohexadienone detail. Sodium 2,G-dimethylphenoxide {I) was (Vc)* have the corresponding structiires IVb selected for initial investigation because steric and IVc, re~pectively.~ hindrance about the phenolic oxygen was likely io enhance nuclear fluorination, and because the relevant chemistry of this phenol is well established. The present paper reports the complex reaction of this phenoxide and also the free phenol with perchloryl fluoride, examines the marked effect of solvent upon the course of reaction, and proposes mechanisms consistent with these observations. Heterogeneous Reaction of the Phenoxide in Hydrocarbon Media.-Passage of perchloryl fluoride into a suspension of sodium 2,6-dimethylphenoxide in dry pentane or toluene a t 0’ resulted in a rapid exothermic reaction which gradually ceased as the reaction mixture became neutral. Workup, followed by chromatography over alumina, gave several products, 01 which recovered Va, X = F IVa, X = F 2,6-dimethylphenol, 2,6-dimethylbenzoquinone and b , X = OH 0 , X = OH the ruby-red 2,2‘,6,Gf-tetramethyl-4,4‘-diphenoquiC, X = CH3 C, X = CHI none (11) were readily identified. The principal The formation of the fluorinated dimer I P a new product, obtained in approximately 20% yield, was a colorless crystalline substance having molecu- according to the usual rule of endo additionlo (6) I n ethyl fluoride t h e coupling between the methyl hydrogens lar formula C I O H ~ ~ OThis ~ F ~compound . exhibited (1) (a) C. E.Inman, R . E. Oesterling and E. H. Tyczkowski, J . A m . Chem. Soc , 80, 6533 (1958); (b) H.Kissman, A. M. Small and M. J. Weiss, i b i d . , 81, 1262 (1959); (c) J. Edwards and H. J. Ringold, ibid., 8 1 , 5262 (19.59). (2) L. Claisen, F. Kremers, F. R o t h a n d E. Tietze, A n n . , 442, 210 (1925); L.Claisen, 2.angew. Chem., 36,478 (1923). (3) T h e reaction of steroidal phenols of t h e estrone series with perchloryl Euoride in dimethylformamide gives good yields of 10-Euoro1,4-estradien-8-ones arising f r o m angular fluorination para to the phenolic function IJ. S. Mills, J . A m . Cham. Soc., 81,5515 (1959); 82, 5882 (196O)l. In contrast t o t h e present study. t h e sodium salt of estradiol gave only a trace of a n y ftuorinated dienone. (4) (a) D. Y.Curtin, R . J. Crawford and M. Wilhelm, ibid., 80, 1391 (1958): (b) D.Y.Curtin and R. R. Fraser, ibid., 80, 6016 (1958). (5) N.Kornblum a n d A. P. Lurk, ibid., 81,2705 (1959).
a n d t h e fluorine is ca. 20 C.P.S. [H. S. Gutowsky, L. H. hleyer and D. W.McCall, J . Chcm. P h y s . , 2 3 , 982 (195511. (7) (a) E. Adler, J. Dahlen and G. Westin, Acta Chem. S c a n d . , 14, 1580 (1980); (b) H.Budzikiewicz, G. Schmidt, P. Stockhammer a n d F. Wessely, Monafsh., 90,609 (1059). (8) T.L. Brown, D. Y.Curtin and R. R. Fraser, J . A m . Chem. Soc.,
80,4339 (1958). (9) It is noteworthy t h a t formation of dimer IVa rather t h a n 111 is consistent with an implication of the mechanism recently discussed for t h e Diels-Alder reaction [R. B. Woodward and T. L. Katz, T e f r a hedron, 6 , 7 0 (1959)], namely t h a t bond formation in the transition s t a t e occurs to give the more highly stabilized intermediate (cf. V I ) which collapses t o product IVa. (10) K. Alder and W. Stein, Angcw. Chcm., 6 0 , 510 (1937). T h e cndo stereochemistry of t h e trimetbyl dimer 1Vc has been established by dipole moment data.8
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ANDREWS.KENDEAND PAULLIACGREGOR
Vol. 83
facile elirninati~n'~ of hydrogen fluoride from IVa suggests that the departing hydrogen and fluorine atoms can readily assume the characteristic trcwzs antiparallel relationship in the transition state.l.* With the relative configurations of these two centers so assigned, the infrared spectrum of the cyclohexenone grouping allows definition of the equilibrium conformation of this system. The carbonyl stretching peak of dimer IVa a t 5.88 is 0.09 p lower than the corresponding band for the trimethyl dimer IVc; this indicates that the fluorine is probably equatorial. These data point Biicbi and E. 31.Burgess, J . A m . Chens. SOL.,83, 4333 (1960)l and have been subjected t o quantum mechanical scrutiny [H. Lahhart and G. Wagniere, IIeia. Chiria. Acta, 42, 2219 (1969); C. F. Wilcox, Jr., S . Winstein and W. G. McMiIlan, J . A m . Chem. Soc.. 82, 5450 (1960)]. T h e present phenol VI1 is of particular interest because of t h e strong bathochromic shift and intensity of its long wave length peak in dilute base; for comparison, t h e ketone iii [E. Wenkert and T. E. Stevens, ihid., 78, 2318 (1930)] shows A, 264, 272, 294 (log L 2.61, 2.61, 2.84). Adler, Dahlen and W e ~ t i n 'have ~ observed similar strong interactions for the ketone iv, A~~~~ 2 8 5 , 311 mp (log c 3.29, 2.89). T h e intensity and t h e wave length of t h e peak above 300 mp f o r such systems appears related t o t h e i;-electron density of the a m matic ring.
MILLIMICRONS.
Fig. 1.--Ultraviolet absorption spectra of: A, dehydrofluorination product VI1 in methanol; B, dehydrofluorination product VI1 in 0.1 iV NaOH; C, 2,3,4,6-tetramethylphenol in 0.1 N NaOH.
has stereochemical implications. Thus it would be predicted that the bulky methyl groups (starred) would be oriented away from the reaction center, as depicted in VI.11 Although evidence is lacking !
on the configuration of the F-C-CHs
I
grouping
CH3 ... Ill
CH:I iv
(13) Fluorine bound t o saturated carhon is normally quite resistant t o base-caiaiyzed elimination. T h e r a t e constant for loss of hydrogen halide from 1-butyl fluoride in ethanolic sodium ethoxide is ca. 10-6 times t h e r a t e for t h e comparable elimination from l-butyl bromide [N. B. Chapman and J. L. Levy, J . Chem. Snc., 1673 (1952)l. This difference is almost entirely due t o t h e more negative entropy of activation for 1-butyl fluoride, which must in t u r n reflect t h e lower entropy of solvation for t h e H3S
