October 1971
PEROXYTRIFLUOROACETIC ACID-BORON FLUORIDE OXIDATIONS
337
Oxidations with Peroxytrifluoroacetic Acid-Boron Fluoride HAROLD HART Department of Chemistry, Michigan State University, East Lansing, Michigan 488g3 Received February 1 , 1971
The common electrophilic aromatic substitution reactions-nitration, halogenation, sulfonation, alkylation and the like-date back to the last century, but it was just over 20 years ago that Derbyshire and Waters’ first considered the possibility of electrophilic aromatic hydyoxylation. The direct production of phenols from aromatic hydrocarbons has long been a desirable synthetic goal, both in the laboratory and commercially, but no useful general method was available. The necessary electrophile would presumably have to be a hydroxyl cation,* OH+ or its equivalent, analogous to NO2+ (for nitration) or R + (for alkylation). Hydrogen peroxide seemed a logical precursor; it was calculated to be about 1% protonated in 10 N acid, and heterolytic
cleavage of the 0-0 bond would supply the desired electrophile. Accordingly, Derbyshire and Waters treated mesitylene (1) with hydrogen peroxide in a mixture of acetic and sulfuric acids. They obtained mesitol (2) in good yield.3 OH
I
1
(BF3.EtzO) with hydrogen peroxide has also been used as an oxidant,’ and although the combination is effective for oxidizing ketones to esters, yields and conversions with aromatic hydrocarbons were low. Organic peracids constitute a second likely source of electrophilic hydroxyl. Electron-withdrawing R groups should facilitate 0-0 bond cleavage in the desired sense (eq 3). RIusgrave and coworkers, who were 40
RC\O?--
One serious difficulty in the controlled oxidation of an arene to a phenol is the fact that the products are, in general, more easily oxidized than the reactants. Mesitylene was a fortunate choice of substrate because all positions ortho and para to the hydroxyl group in the product are substituted, thus retarding (but not preventing, vide i n f y a ) further ~ x i d a t i o n . ~ A Lewis acid (1) D. H . Derbyshire and W. A . Waters, Nature, 165, 401 (1950).
(2) This species has been detected spectroscopically (for references, see G. Hereberg, “Molecular Spectra and Molecular Structure. I. Spectra of Diatomic Molecules,” Van Nostrand, New York, N. Y . , 1950, p 56l), but its existence in solution has never been established. I n this paper me will use the symbol O H + for convenience t o represent the electrophile. The actual electrophile is probably not O H + (see, for example, R. Curci and J. 0. Edwards, Org. Peroxides, 1, 213 (1970)), but leads t o an intermediate carbonium ion with the same structure that would be expected were the electrophile OH +. Kinetic studies which might establish the true nature of the electrophile have not been performed. (3) The brief note was never followed by a full paper, and experimental details are lacking, but the result has been verified in our laboratory and yields can be >SO%. (4) Recently diisopropyl peroxydicarbonate-cupric chloride6 and HF-HZOZin the presence of COz under pressure6 have been found effective with less substituted arenes such as benzene and toluene. See also S. Hashimoto and W. Koike, BtdZ. Chem. Soc. Jup., 43, 293 (1970).
-
+ OH’
RC0,-
(3)
the first to use this approach to direct aromatic hydroxylation,* selected peroxytrifluoroacetic acid (eq 3, R = CF,) because of its known excellent oxidizing proper tie^.^ With mesitylene as the substrate, a good yield of mesitol was obtained (after 24 hr at 0’). However, although the yield was high, the conversion was low (17-25%).1° The low conversion and long reaction time were somewhat discouraging from the synthetic viewpoint. I t was our good luck to try the fourth remaining combination of reagents, ie., an organic peracid and a Lewis acid (for example, BF,). We thought that coordination with either the carbonyl or ether oxygen might facilitate 0-0 bond cleavage in the desired sense. With this in mind, we tried oxidizing the old standby, mesitylene, with CF3C03H and BF,. The 6+
2
OH
I-
/%--BF, CF ,C
‘3- OH
and/or
//O CF,C 6-
‘&OH /+
BF‘~
reaction was exothermic and virtually complete on mixing the reagents, even at -40’, and the yield of mesitol was essentially quantitative, limited only by the skill of the experimenter. N o other Lewis acid that we tried has been so effective or easy to use as BF3 (gaseous, or more conveniently the ethereate). We have found peroxytrifluoroacetic acid-boron
(5) M. E . Kura and P. Kovacic, J . A m e r . Chem. SOC.,8 9 , 4960 (1967). (6) J. A. Vesely and L. Schmerling, J . Org. Chem., 35, 4028 (1970). (7) J. D. McClure and P. H . Williams, {bid., 27, 24 (1962). (8) R . D. Chambers, P. Goggin, and W. K. R. Musgrave, J . Chem. SOC., 1804 (1959). (9) W. D. Emmons and A . S. Pagano, J . A m e r . Chem. SOC.,77, 4557 (1955), and earlier papers. (10) The reagent reacted more efficiently with more reactive substrates. Thus 2,6-xylenol was converted (77%) to 2,6-dimethyl1,4-beneoquinone. This illustrates, incidentally, the ease of further oxidation when a position para to the hydroxyl group is unsubstituted.
HAROLD HART
338
fluoride to be a useful, versatile oxidant of T systems. The reagent” delivers a potent electrophile which attacks substituted as well as unsubstituted positions on aromatic rings. The oxidation products are frequently difficult t o obtain in other wags and certain of them, especially highly substituted cyclohexadienones, have proved valuable as synthetic intermediates for aromatic, small-ring, and bicyclic compounds. Recent use of the reagent with alkenes suggests that it may also be useful in aliphatic syntheses. We present here a brief account of this development and a summary of results to date.
Direct Aromatic Hydroxylation Although the initial driving force for devising the CF3C03H-BF3reagent was to effect one-step electrophilic hydroxylation of arenes to phenols, this application has not, in fact, become its most important use. Although mesitylene (1) and isodurene (3) were readily hydroxylated in good yield, less substituted hydrocarbons (benzene, toluene, etc.) gave mainly tars, due to
VOl. 4
1-H-
4-H’
7
8
The yields of 7 and 8 represented only 9% of the prehnitene oxidation products, but the formation of these products, particularly 8, led us t o try a substrate in which only attack at a substituted position was possible. The result was rewarding. Hexamet hy1benzene (9) gave the corresponding 2,4-cyclohexadienone 10 in over 90y0 yield.16s17 The pentadienyl cation intermediate has no competition from alternative stabilization paths and leads to 10, by methyl migration
9
10
and proton loss, in high yield. 3
4
further oxidation of the initially produced p h e n ~ l s . ~ - ~ Extension of the reaction to other highly substituted arenes disclosed the fact that the reagent was suffiThe reaction is quite general, as the following exciently “hot” to attack already substituted positions. amples will illustrate. Hexaethylbenzene gives a This reaction proved particularly useful synthetically hexaethyldienone (eq 9).16 Halopentamethylbenxerie;.i and diverted our attention to the extent that the potential of the reagent for synthesizing phenols has really not yet been fully explored.
Electrophilic Attack at Substituted Positions Oxidation of prehnitene ( 5 ) gavel2 not only the expected phenol 6, but small amounts of an isomeric phenol, 7, and cyclohexadienone 8 (as well as other
11
12
give halocyclohexadienones (eq 10).
The strained
(13) Actually there were two earlier reports which indicated oxidative electrophilic attack a t already substituted positions. Musgrave* obtained small amounts of the trimethylquinone i from mesitylene and CFICOIH; the structure requires a methyl migra-
5
+ 6
$ 7
(5)
+
@
+ other products
8
products, discussed in the following section). Products 7 and 8 are most easily rationalized by assuming electrophilic attack at an already substituted position, followed by Wagner-lleerwein methyl migration in either of the two possible senses and proton loss.13 (11) L. F. Fieser and >I. Fieser, “Reagents for Organic Synthesis,” Wiley, New York, N . Y . , Vol. I, 1967, pp 824-826; also, T’ol. 11, 1969, p 316. (12) H. Hart and C. A . Buehler, J . Org. Chem., 2 9 , 2397 (1964).
i
ii
...
111
tion. McClure’4 obtained ii, the Diels-Alder dimer of iii, from the oxidation of 2,6-xglenol. I n this case (and in the related Wessely acetoxylation of phenols’j) the carbonyl oxygen of the dienone is derived from the phenolic hydroxyl group, whereas in 8 it is derived from the oxidant. (14) J. D . McClure, J . Org. Chem., 28, 69 (1963). (15) For a review, see A. J. Waring, Advan. Alicyclic Chem., 1, 129-256 (1966), especially pp 162-167. (16) A. J. Waring and H. Hart, J . Amel. Chem. Soc., 86, 1454 (1964); H. Hart, P. M. Collins, and A. J. Waring, ibid., 88, 1005 (1966). (17) H. Hart, R . M. Lange, and P. M . Collins, Org. Syn., 48, 87 (1968). (18) Unpublished results with D. Shapiro.
PEROXYTRIFLUOROACETIC ACID-BORON FLUORIDE OXIDATIONS
October 1971
339
rate. The most likely route to 21 therefore seems to be attack at position c of 17, followed by three successive Wagner-Meerwein 1,2 shifts (eq 14). 13, X = C1, Br
14
17< .
fused ring system in 15 survived the o ~ i d a t i o n , ' ~ though 16 was obtained in only modest yield. Benzo-
15
16
17
I
A
I)
18 (36%:)
19 (20%)
.lc
21 ( 206 )
25
(15)
U 26
0 (13)
10
0
24
conjugated dienone, requires special comment. This compound could arise from 18 via protonation, two methyl migrations, and deprotonation. However, 18 is stable under the oxidation conditions. Though such rearrangements are known (eq 13),22,23they usually 0
The conjugated spirodienone 23 was not isolated, and evidence from other experiments indicates that such compounds isomerize extremely rapidly in acid to their cross-conjugated isomers. For example, 24 (the trimeric dehydration product of cyclohexanone) gave only the cross-conjugated product 25 when oxidized at O", though when the reaction was carried out at -65" the linearly conjugated dienone 26 was obtained.24 The reason why spirodienones such as 23 or 26 rearrange much more rapidly than dialkyl dienones such as 10
n
0
20 ( 24%1
*
P
cyclobutenes may undergo considerable ring opening and polymerization in the presence of electrophiles,2o and this may account for the low yield in eq 11. With a larger fused ring (17) the reaction is cleaner, and products from electrophilic attack at all three possible positions were isolated.21 The mechanism for the formation of 18-20 is unexceptional, but the isolation of 21, a cross-conjugated rather than linearly
la
t;
22
require considerably stronger acid to proceed at a rapid (19) R. J. Bastiani, D. J . Hart, and H . Hart, Tetrahedron Lett., 4841 (1969). (20) J. B. F. Lloyd and P. A. Ongley, Tetrahedron, 20, 2185 (1964). (21) R . J. Bastiani, Ph.D. Thesis, Michigan State University, 1970. (22) H . Hart and D. W. Swatton, J. Amer. Chem. SOC.,89, 1874 (1967). (23) V. G. Shubin, V..'l Chzhu, A. I. Rezvukhim, and V. A . Koptyug, Bull. Acad. Sci. USSR, Div. Chem. Sci., 1999 (1966); V. G. Shubin, V. P. Chzhu, A. I. Rezvukhim, A. A. Tabatskaya, and V. A. Koptyug, ibid.,2264 (1967) ; R . F. Childs, Chem. Commun., 946 (1969).
is not yet known. Highly substituted naphthalenes can be oxidized by CF3COaH-BF3 to benzocyclohexadienones. With 1,2,3,4-tetramethylnaphthalene (27), oxidation occurred almost exclusively in the substituted ring and, as expected with electrophilic reactions of naphthalenes, attack at C-1 (to give 28 and 30) was favored over attack at C-2 (to give 29), by 4 : l.25 The diketone 30 arises solely from further oxidation of 28, not 29, as shown by the separate quantitative oxidation of 28 --t 30 and by the fact that treatment of 27 with excess oxidant gave only 29 and 30. An unusual result was obtained with octamethylnaphthalene (31).26 This molecule is quite strained, (24) H. Hart and D. C. Lankin, J. Org. Chem., 33, 4398 (1968). (25) H. Hart and R. K. Murray, Jr., ibid., 32, 2448 (1967). (26) Unpublished results with A. Oku.
a
HAROLD HART
340
\
an already substituted position is favored 2 : 1 statistically, and the methyl substitution pattern is nearly identical for attack at either position, although it is our experience that methyl groups are usually somewhat more effective at stabilizing pentadienyl cations when located at the central carbon atom (as one of them would be, for attack at a substituted position). Methyl migration occurs preferentially toward the adjacent substituted position, giving 35; no isodureriol (4) was
CF,CO,H-BF,
/
\
-E',65% yield
a t 83% conversion
+
28 (61%)
27
29 (21%)
VOl. 4
30 (20%)
due to interactions between the methyl groups in the peri positions.27 Attack occurred almost exclusively at C-1 and, interestingly, the carbonium ion intermediate underwent not only the expected methyl migration to give 32 but aryl migration to give the acetylindene 33. Analogous ring contraction in simpler systems has not yet been observed.
-
=OH
-H+
