662
J. Org. Chem. 1992,57,662-666
Thiophenol-PromotedRadical Chain Reduction of a-Substituted Isobutyrophenones by 1,3-Dimethyl-&phenylbenzimidazoline Dennis D. Tanner* and Jian Jeffrey Chen' Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2 Received M a y 29, 1991
The reductions of a-haloacetophenones and a-halopropiophenones by 1,3-dimethy1-2-phenylbenzimidazoline (DMBI) have been reported to proceed via an electron-transfer free-radical chain mechanism. The reduction of a-haloisobutyrophenonesdid not proceed by the chain sequence. We now report that initiated reductions of a-bromo- and a-chloroisobutyrophenonea(IIIa,b)have been found to be promoted by the addition of thiophenol. Ieobutyrophenone was formed as the major product via a free-radical chain process. During the PhSH-promoted DMBI reduction of IIIa,b a minor product, a-(pheny1thio)isobutyrophenone (N), was also formed via nucleophilic substitution. The chain propagation steps involve the efficient hydrogen atom transfers between PhCOCMe2' and PhSH and between PhS and DMBI. The facile hydrogen transfer between PhS' and DMBI was confiied by carrying out the radical-chain reduction of PhSSPh with DMBI.
Introduction The reduction of a-bromo- and a-chloroacetophenone (Ia and Ib) and a-bromo- and a-chloropropiophenone (IIa (DMBI) and IIb) by 1,3-dimethyl-2-phenylbemimidizoline was recently reported.2 The reduction products, acetophenone and propiophenone, were formed by an electron-transfer hydrogen atom abstraction chain mechanism (see Scheme I).2 The reduction of a-bromo- and a-chloroisobutyrophenone (IIIa and IIIb), however, did not appear to proceed by a chain sequence since the addition of either an initiator (AIBN) or an inhibitor (dinitrobenzene, DNB), additives which had been an effective chain initiator and inhibitor for the reduction of the primary (Ia,b) and secondary (IIa,b) halo ketones, did not significantly affect the yield of the reduction products. The tertiary halo ketones, IIIa,b, were involved in the radical process since they acted as efficient inhibitors when they were present during the reduction of the a-haloacetophenones and ahalopropiophenones. The observation that chain reduction did not take place with the a-haloisobutyrophenones was rationalized by assuming that hydrogen atom transfer between the tertiary radical PhCOCMe; and DMBI was too inefficient to carry the chain (eq 3). It was anticipated that the chain reaction would be facilitated by the addition of a chain-transfer agent which itself produces a radical that could carry the chain. As anticipated, the addition of thiophenol increases the yield of the reduction products significantly. The present report describes a study of this enhanced reduction. Results and Discussion Reduction of a-Haloisobutyrophenonesby DMBI in the Presence of PhSH. The DMBI reductions of the a-haloisobutyrophenones (IIIa,b) were carried out using the same conditions as previously reported for the DMBI reductions of Ia,b and IIa,b (degassed, THF, 61 oC).z Radical initiation (AIBN) and inhibition Cp-DNB) were used to establish whether a free-radical chain mechanism is operative in the PhSH-promoted reduction. The results of these studies are summarized in Table I. The reduction of a-bromoisobutyrophenone (IIIa) which had been reported2as relatively unreactive toward DMBI (reactions 1-3, Table I) was significantly accelerated by the addition of thiophenol (reactions 5-10). An optimum yield of reduction product was obtained when at least 2 equiv of thiophenol were used. In addition to the reduction (1) Killam predoctoral fellow, 1987-1990. (2) Tanner, D. D.; Chen, J. J. J . Org. Chem. 1989,54, 3842.
0022-3263/92/1957-0662$03.00/0
product, isobutyrophenone, a-(pheny1thio)isobutyrophenone (IV) was produced as a minor product (-1-5%). In the presence of p-DNB, the formation of the reduction product was inhibited (reactions 6,8,lo), but the yield of the substitution product IV increased significantly. Two competitive processes appear to be operative: the reduction product, isobutyrophenone, is formed by a free-radical chain process, while the substitution product, the thio ketone IV, is formed by a heterolytic substitution. In the absence of DMBI, IIIa was unreactive toward PhSH even in the presence of AIBN (reaction 11,Table I). Since DMBI and PhSH are required both for the radical-chain reduction and heterolytic substitution of IIIa, the nucleophilic substitution appears to proceed via the thiolate anion, PhS-, eqs 5 and 6.
F N H
xp,+
A*'
xph
N
PhS-
+ PhCOCMe2X
H
+
PhSH
CHl
H
PhS-
(5)
N
-
I CH3
PhCOCMqSPh
+ X-
(6) The reduction of a-chloroisobutyrophenone (IIIb)was enhanced by PhSH (reactions 12-17), albeit the thermal reaction was much slower than that of the bromide IIIa. Nevertheless, the reduction could be inhibited by DNB (reaction 16) and initiated by AIBN (reaction 17). The yield of the heterolytic substitution product (IV) also increased in the presence of DNB (reaction 16). Scheme I1 rationalizes both initiation (AIBN) and inhibition (DNB) and seems to indicate that the thiophenol-promoted reduction proceeds by a short-chain process, Table I, reactions 5-10. The two main chaintransfer steps involve hydrogen atom transfer from PhSH and DMBI (eqs 8 and 9). Although hydrogen abstraction form PhSH is well documented and hydrogen abstraction by PhS' from C-H has been observed, it is limited by re~ersibility.~*~ The major portion of the thiyl radicals produced results in dimerization (reaction 12). A similar mechanistic scheme involving hydrogen abstraction from RSH by an aminyl radical, followed by hydrogen abstraction from the acarbon of an amine by the RS' radical, was proposed to explain the catalytic effect of thiols in the photoreduction of benzophenone by amine^.^ In order to show unam(3) Kice, J. L. In Free Radicals; Kochi, J. K., Ed.; Wiley: New York, 1973; Chapter 24, pp 718-22. (4) Tanner, D. D.; Wada, N.; Brownlee, B. G. Can. J . Chem. 1973,51, 1870.
0 1992 American Chemical Society
J. Org. Chem., Vol. 57, No. 2, 1992 663
Thiophenol-Promoted Radical Chain Reduction
aNxH aNxH a'Nx- a:)--€% Scheme I
943
p
@XH
PhcoCR1R2x +
Initiation
r;' Ph
PhC&R'R'
p
PhCOCR'R'X
3
(?I3
r;' Ph
+
+
a
3
H y P h CH3
p
3
p
+
+
PhSH
'
-
Ph(!!-CR'R2X
CH3
o N x H N Ph
2 PhS'
PhCOCR'R'H
0-
3
N Ph
CH3 PhS'
Ph-C-CR'R'X
+ X-
+
PhdR'R'
I
+
/r;'Ph CH3
CH3
0-
0I
3
+
PhSSPh
Table I. PhSH-Promoted Reduction of PhCOCMe,X - (1IIa.b) . . . by - DMBI
PhCOCMeX Br (IIIa)
C1 (IIIb)
reaction 1 2 3 4 5 6 7 8 9 10
condns'
11
96 hb 96 h, 4% AIBNb 96 h, 5% p-DNBb 104 h 104 h, PhSH (0.5equiv) 104 h, PhSH (0.5equiv), 10% DNB-p 35 h, PhSH 35 h, PhSH (1 equiv), 10% p-DNB 20 h, PhSH (2equiv) 20 h, PhSH (2equiv), 9% p-DNB 104 h, PhSH (2 equiv), 8% AIBN'
12 13 14 15 16 17
77 hb 77 h, 3% AIBNb 77 h, 3% p-DNBb 27 h, PhSH (2equiv) 27 h, PhSH (2equiv), 6% p-DNB 27 h, PhSH (2equiv), 6.7% AIBN
PhCOCHMe2 5.4 11.4 12.2 19.1 79.5 0.2 46.9 2.2 92.7 0.7 2.6 4.7 14.8 1.0 14.5 0.0 96.5
(IIIa,b)
89.6 79.7 79.7 63.4 20.5 57.0 43.0 63.4 52.0 92.9 84.8 81.7 92.9 77.8 79.9
PhCOCMez SPH (IV)
4.0 18.6 4.6 35.6 1.7 22.2
8.0 32.7 2.6
"All the reactions were carried out in THF at 61 "C with [PhCOCMe2X]:[DMBI]= 1:2 except where specified in the table [IIIa,b] = 0.05 M.
[PhCOCMe2X]:[DMBI] = 1:l. 'No DMBI was used.
Tanner and Chen
664 J. Org. Chem., Vol. 57, No. 2, 1992 Table 11. Reduction of PhSSPh bs reaction solvent condns; PhSH 18 THF 0.9 f 0.9 19 7% AIBN 69.0 0.4 20 CsHs 21 10% AIBN 72.2 f 0.2
*
DMBI at 61 O C PhSSPh PhSCHt 73.4 f 10 2.4 f 0.7 20.7 f 3.0 6.4 0.4 94.0 f 9.0 24.7 f 5.0 1.2 f 0.2
Scheme I11 +
CH3 A H
CH3
A
XPh= PhSH +
CH3
N
N
>Ph
+
PhSSPh
N
-
PhS.
+
I biguously that the abstraction reaction, eq 9, does occur, the reduction of phenyl disulfide by DMBI was investigated. DMBI Reduction of PhSSPh. The reductions of PhSSPh by DMBI were carried out in THF and in C6H6 at 61 "C. The results are shown in Table 11. The reduction can be initiated by AIBN to give thiophenol as the major product. Small amounts of methyl phenyl sulfide and 1-methyl-2-phenylbenzimidazole (
