8074
J . Am. Chem. SOC.1991,113, 8074-8081
Fragmentation of Substituted Acetophenone and Halobenzophenone Ketyls. Calibration of a Mechanistic Probe Dennis D. Tanner,* Jian Jeffrey Chen,’,” Lucia Chen,2band Christine Luelo” Contribution from the Department of Chemistry, University of Alberta, Edmonton, Alberta T6C 2C2, Canada. Received March 14, 1991
Abstract: Disubstituted acetophenones, XC4H4COCH2Y,and benzophenones, XC4H4COC6H4Y,are used to measure the cleavage rate constants, kru, of a series of a-substituted acetophenone ketyls and ring-substituted benzophenone ketyls. The cleavage rate constants can be determined from the competitive rates of fragmentation, k W / k r x , of a series of ketyls, [XC6H4COCH2Y]’-and [XC6H4COC6H4Y]:-,since the rate constants, krx,for a number of ketyl fragmentations have been electrochemically determined. Ring fragmentation is not significantly affected by substitution at the a-position of the acetophenone nor on the opposite ring of the benzophenone. The ketyls are formed by the reaction of 1,3-dimethyl-2-phenylbenzimidazoline (DMBI) with the disubstituted ketones. Ketyl fragmentation can be used as a diagnostic chemical probe for reactions of ketones suspected of having ketyl intermediates.
Introduction Electron-Transfer-Fragmentation Reactions of Substituted Acetophenones. a-Haloacetophenones have been used successfully as chemical probes to distinguish between electron transfer-hydrogen atom abstraction and hydride-transfer mechanisms in reductions by organotin hydride^,^ o r g a n ~ s i l a n e s ,1~,Cdihydropyridine^,^ enzyme (HLADH) mediated N A D H reductions: and the reductions of ketones by 1,3-dimethyl-2-phenylbenzimidazoline (DMBI).’ The mechanistic pathways for reduction by the reducing agent, ZH, can be distinguished on the basis of the products formed since acetophenone is the product of homolytic reduction and the halohydrin is the product of the heterolytic process. The mechanism used to rationalize the products formed from the homolytic pathway involves an electron transfer (ET) as one of the chain-propagation reactions, Scheme I. Originally, the ketyl radical anion, i, was proposed as an intermediate in the reaction, eq 1 ,3d S~bsequently:,~the ketyl was proposed to fragment by dissociative ET, since fast cyclic voltammetry (CV) at IO3 V/s showed only one irreversible wave and a second reversible wave assigned to the reversible reduction of the enolyl radical to its anion.6 Enzymatic reduction reactions of the a-haloacetophenones by NADH produced only optically pure halohydrins (heterolytic reduction products).6 However, in order to differentiate between ET followed by very fast hydrogen atom transfer between radical ion pairs, and a hydride-transfer process, it is important to establish whether ET to an a-haloketone is a dissociative process. Recently the results of the electrochemical reduction of a number of ring-substituted acetophenones and benzophenones have been r e p ~ r t e d . * * ~When J ~ the substituents were halogens, the rate constants for fragmentation of the halide anions from the intermediate ketyls, koc, were determined. The cleavage rates of a-substituted acetophenones, however, have not been determined. (1) Taken in part from the Ph.D. Dissertation of J. J. Chen, University of Alberta, 1990. (2) (a) lzaak Walton Killiam, predoctoral fellow, University of Alberta, 1987-1990. (b) Women in Scholarship, Engineering, Science and Technology, WISEST Sumer Research Fellowship, 1989. (c) NSERC summer undergraduate research fellow, 1990. (3) (a) Tanner, D. D.; Diaz, G. E.;Potter, A. J . Org. Chem. 1985, 50, 2149. (b) Tanner, D. D.;Singh, H. K. Ibld. 1986, 51, 5182. (4) Yang, D.; Tanner, D. D. J. Org. Chem. 1986, 51, 2267. (5) Tanner, D. D.;Singh, H.K.;Kharrat, A.; Stein, A. R. J . Org. Chem. 1987, 52, 2142. (6) Tanner, D. D.; Stein, A. R. J . Org. Chem. 1988, 53, 1642. (7) Tanner, D. D.; Chen, J. J. J . Org. Chem. 1989. 54, 3842. (8) (a) Andrieux, C. P.; Saveant, J. M.; Zann, D. N o w . J . Chim. 1984, 7, 107. (b) Andrieux, C. P.;Hapiot, P.; Saveant, J. M. J . f h y s . Chem. 1988, 92, 5987. (9) Wipf, D. 0.; Wightman, R. M. J . Phys. Chem. 1989, 93, 4286 and
references cited therein. (IO) (a) Sucheta, A.; Rusling, J. F. J . f h y s . Chem. 1989, 93, 5796-5802. (b) Aalstad, B.; Parker, V. D. Acta Chem. Scund. 1982, 836, 47-52. (c) Nadjo, L.; Saveant, J. M. J . ElectroanuL Chem. 1971, 30, 41.
Scheme I 0-
0
II
+
PhCCHZX
Z’
I
4
[Ph$CHzX]
+
Z+
i U
II
+
PhCCH2.
0
X-
+
Z+
(1)
0
II
+
PhCCH2*
ZH
II
6
PhCCH3
+
Z*
(2)
Scheme I1 n
0-
0>iCHzY - ’X
0 >$CH2* - ’X
>COCH2*
+
ZH
-
+ Z*
>COW3
(6)
- ’X
- ’X
Scheme I11 0
@!C,H4* - ’X
0
-
0 D ! P h
(7a)
-X ’
0
If one assumes that substitution a t the a-position will not appreciably affect the rates of cleavage of a ring-halogenated substrate or vice versa, then the determination of the relative rates of competitive intramolecular fragmentation allows the calculation
0002-7863191/ I 513-8074%02.50/0 0 1991 American Chemical Society
J . Am. Chem. SOC.,Vol. 113, No. 21, 1991 8075
Acetophenone a n d Halobenzophenone Ketyl Fragmentation
Table I. DMBl Reduction of a-Substituted Acetophenones Ia-e" substrate product (%P PhCOCHzY reaction Ia-e conditions PhCOCH3 PhCOCH2Y 3.2 f 2.0 1 Is, Y = OCOPh 60 h, C6H6 90.0 f 0.1 2 Ib. Y = OCOCH3 60 h, C6H6 55.1 f 1.0 45.3 1.0 48 h, AN 75.6 f 0.3 2.6 f 1.0 3 IC, Y = OPh 4 Id, Y p-TolS02 48 h, THF 94.8 f 0.7 48 h, THF 86.1 f 0.7 12.3 f 4.0 5 le, Y = SPh "All reactions were carried out at 61 OC in the dark with [Ia-e]/ [DMBI] = 0.05-0.06 M. In the absence of AIBN ( S % ) , almost no reaction occurred (yield 470 two products were formed from both reactions (reaction 23, Table IV, or reaction 34, Table v ) . Control reactions carried out in the absence of Ru(bpy)?+ gave only small amounts of the reduction products (reaction 24, Table IV, or reaction 35, Table V). Since the R~(bpy),~+-sensitized reductions of IIIf and IIIk gave essentially the same product ratios (Le,, competitive cleavage rates) as the corresponding product ratios obtained by using DBPO (reactions 22 and 23, Table IV, reactions 33 and 34, Table V), the Ru(bpy),2+-sensitized reduction most probably also proceeds through a similar E T mechanism. As predicted, the product ratios are not dependent upon the nature of the electron donor. The temperature dependence of the relative cleavage rates was found to be small (see reactions 21-23, Table IV, and reactions 31-34, Table V). It is justified, therefore, to use the electrochemical rates determined a t room temperature and the relative cleavage rates (or product ratios) determined chemically a t 61 "C to calculate the new cleavage rate constants a t room temperature. In order to substantiate the validity of the assumption that the fragmentation rate of Y was not appreciably affected by X or that the fragmentation rate of X was not effected by Y, another determination of the same value (k,) was carried out by using a different substituent, X. The cleavage rate of o-chloroacetophenone was reported to be. 3 X IOs s-l in AN,9 and that of p-bromoacetophenone was 3.2 X I O7 S-I (DMF).* The intramolecular competitive reductions of o-chloro-a-phenoxyacetophenone(IIIg) and p-bromo-a-phenoxyacetophenone (IIIh) gave an average cleavage rate constant of (9.5 f 6.0) X IO6 s-] for a-phenoxyacetophenone ketyl; see reactions 21-23 and 25, Table IV. The reduction of apdibromoacetophenone (IIIa) and achloro-p-bromoacetophenone (IIIb) gave only p-bromoacetophenone (reactions 13-16, Table IV). The limit for detection of the a-haloacetophenones was experimentally estimated (GC and G C / I R ) to be IO9 s-', could be placed on the cleavage rates of the a-bromo- and achloroacetophenone ketyls. An estimated value, 99 6.3 38.8 20 OC, 3.3% sens,l hu,h 12 h 23 14.8 X IO6 >99 0.65 1.4 24 20 OC, hu,h 12 h 34.6 Illg, X = 0-CI, Y = OPh 20 OC, 1.7% sens,R hv," 35 h 97 0.6 19.2 X IO6' 25 1.3 26 >98 20 "C, hu,h 35 h 44.5 61 OC, 5% AIBN, 59 h 2.7 5.3 x 108 IIIh, X = p-Br, Y = p-TolSO, 100 27 8.0 Illi, X = p-Br, Y = SPh 61 "C, 2% AIBN, 48 h 99 9.3 x 106 31.8 28 "All reactions were carried out in A N in the dark, except where specified in the table, with less than 1 equiv of DMBI. [IIIa-i] = 0.05 M. * I n the absence of AIBN, Ilk-i showed little reaction (99 4% Ru(bpy),*+,96 hd 57.0 41 98 h (no DMBI)' 3.2 42 0.34 100 98 h (with DMBI)' 66.79 43 44
IVc, X = 2-CI, Y = 3-Br
45
6.2 56.68
0.5 4.2
100
2% Ru(bpy),2+,68 hd
DMF, 120 h" DMF, 2.6% Ru(bpy)s2+,120 h" 4% AIBN, dark, 61 OC'
28.1 52.1h 15.4
0.96
>99 97
68 hd
88i
ref 1Oa
10b 1 Ob
8a 1oc 10b 10b 1 oc 1oc
10b 9 1oc 8a 1Ob
10b
product ratioC V/VI
216 f 21 106 215 57 196f 1 av 172 44 12 14f 1 av I 3 f 1
29 68 f 21 28 0.54 48 av 42 f 18 g All the reactions were carried out in AN with less than 1 equiv of DMBI, except where specified in the Table; [IV] = 0.03-0.05 M. *The product yield of one representative run. C A n average of two independent runs, and the error represents the standard deviation from the mean. "Irradiation with two 200-W incandescent lamp bulbs through a filter solution of NaNO3-NaOH-Na2C~,O7. Ishitani, 0.;Yanagida, S.; Takamura, S.; Pac, C. J . Org. Chem. 1987, 52, 2790. 'The reactions were carried out in an AN/THF ( 3 / l , v/v) mixture. /Irradiation with two 200-W incandescent lamp bulbs through Pyrex filter. #About 0.2-0.4% yield of benzophenone was also detected by GC/IR. h4.0%yield of benzophenone was also detected by GC/IR. 'The reactioins were carried out in the dark at 61 OC in an AN/C6H6 (1/2, v/v) mixture. 'In the event that all of the missing material was either V or VI, the calculated rates will only differ by a factor of
