[CONTRIBUTION FROM
THE GEORQE
HERBERT JONESLABORATORY OF THE CHICAGO]
UNIVERSITY OF
FACTORS INFLUENCING THE COURSE AND MECHANISM OF GRIGNARD REACTIONS. XVII. INTERCHANGE OF RADICALS IN THE REACTION OF GRIGNARD REAGENTS AND ORGANIC HALIDES IN THE PRESENCE OF METALLIC HALIDES M. S. KHARASCH
AND
CHARLES F . FUCHS
Received April 7, 1945
In the following paper, the term “radical interchange” will be applied to reactions of the following types:
(A) RMgX (A’) RMgX
+ R’Y + R‘Y
$ R’MgX
R‘MgY
+ RY or +RX
Gilman and Jones (1) found that no such interchange occurs when the following Grignard reagents and organic halides are heated together. (a) (b) (c) (d) (e)
+
CaHsCHzMgBr CeHsBr (CBHS)&M~C~C & a r CsHsMgBr CaH&H&1 GHhMgBr (CaHs)sCCl CGHsCHzMgBr (CeHS)sCC1
+ +
+
+
In each instance, the only acid formed when the mixture is treated with carbon dioxide is the one to be expected from the Grignard reagent originally present. When CY-bromo-2 ,4,6-trimethy1-3,5dibromoisobutyrophenoneis treated with methyl- or ethyl-magnesium bromide, the a-bromine atom is replaced by an atom of hydrogen. Fischer, Oakwood, and Fuson (2) ascribe this replacement to the intermediate formation of the enolate (I).
(1) A similar explanation is offered by Lowenstein and Shuster (3)to account for the formation of triphenylethanone by the action of methyl-, ethyl-, or phenylmagnesium bromide on a-bromotriphenylethanone.
GFUGNARD REAGENTS AND ORGANIC HALIDES
293
The reactions cited are, however, not simple replacements but oxidationreduction chain reactions involving in each stage a single electron transfer. It is unfortunate that the gaseous products were not determined when methyl or ethyl Grignard reagents were used. However, the formation of biphenyl from (11) is in agreement with the explanation just given.' In only three cases reported in the literature, is there unambiguous evidence of radical interchange (4, 5). Pr6vost (4) has demonstrated that, when ethylmagnesium bromide is mixed with cinnamyl bromide, there is a definite increase in the amount of ethyl bromide present in the mixture. Umnova (5) has proved that the following reaction takes place when a! ,a'-dibromoisobutyrone is treated with phenylmagnesium bromide.
CHa '\
0 CHa
I
BrC-C-CBr /
d&
I
I
+ CsHsMgBr +
CH, CHQ 0
I
I
CaHsC-C-CMgBr
I
CHS
CHs
I I
+ CsHsBr + MgBra
CHs
Urion (6) has stated that when an equimolecular mixture of ethylmagnesium bromide and cyclohexyl bromide is allowed to stand for 24 hours, a radical interchange occurs. His evidence is that, when the mixture was hydrolyzed after standing, 12% of cyclohexane was obtained. In confirmation of this observation, 10% of hexahydrobenzoic acid was here obtained from a similar mixture by treating it, after it had stood 36 hours, with carbon dioxide. However, we cannot agree with Urion as to the results obtained when cyclohexyl bromide and ethylmagnesium bromide are mixed in ether solution, and 66% of the ether present is then promptly removed by distillation. He reports a 40% yield of cyclohexane. But here, treatment with carbon dioxide of a mixture similarly prepared and similarly concentrated yielded only a negligible amount of hexahydrobenzoic acid. The discrepancy between the two results may, however, be explained. It has been observed that, when ethylmagnesium bromide is heated in ether solution with bromocyclohexane, a mixture of ethane, ethylene, cyclohexane, and cyclohexene is formed (7). It may well be that Urion failed to detect the first two of these components and mistook the mixture of the last two (which boil within a few degrees of one another) for pure cyclohexane. The work of Wuyts (8) on the radical interchange between Grignard reagents and a!-bromocamphor, since it lacks experimental details, is inconclusive. The investigation of these reactions is being repeated in this laboratory. Radical interchange reactions of Grignard reagents and organic halides in the 1 The mechanism of the reactions cited will be fully discussed in a forthcoming publication.
294
M. S. KHARASCH AND C. F. FUCHS
TABLE I RADICAL EXCHANQE REACTIONS BETWEEN GBIQNARDREAQENTS AND ORQANIC RADICALS IN THE PRESENCE OF METALLIC HALIDES
MOLE % OF ULIDE CON)ENBED
OPOANIC HALIDE OP HYDPOCAXBON
ACID FOPYED BY M I C A L EXCHANGE
(1) *n-C,HdMgBr.. (2) n-C4HpMgBr.. . (3) *n-C4HoMgBr..
CoCla (1%) COClt (26%) COCll (1%)
14 45 8
(4) *CHaMgBr... . .
COClZ (1%)
22
(5) C H N g B r . . . . . .
COCL (1%)
-
(6) *CHsMgBr.. . . .
COCll (1%)
99
(7) CHaMgBr
COClZ (1%)
34
(8) n-CJhMgBr
coc12 (1%)
60
(9) *CsHsMgBr.. . . (10) C H a g B r
CoCL (1%) COClZ (1%)
60 85
(11) CHsMgBr.. . . . .
FeCl: (2%)
85
(12) *n-CcHsMgBr
coc12 (4%)
96
Triphenylacrylic acid (14%)'
(13) CHSMgBr.. . . . .
COClZ (3%)
57
Triphenylacrylic acid (32%)
(14) CHsMgBr
FeCla (3%)
37
Triphenylacrylic acid (13%)
(15) CHsMgBr
coc12 (3%)
37
Triphenylacrylic acid (19%)
-
CsHsCOOH (7%) COH&OOH (None) CHrOCeHL!OOH (4%) ( p )-CsHsCsH4COOH (1%) Fluorenecarboxylic acid (None) 9-Fluorenecarboxylic acid (10%) 8-Phenanthrenecarboxylic acid (3%) Triphenylacetic acid (1.5%) n-Valeric acid (3%) Phenylpropiolic acid (None)a Phenylpropiolic acid (None)b
Phenylpropiolic acid was absent but 1-phenyl-1-propene (75%) and 1,4-diphenylbutadiene (8%) were isolated. There was also a small amount of tar. b A 10% yield of 1-phenyl-1-propene was isolated. This amount corresponds quantitatively t o the amount of w-bromostyrene consumed in the reaction. Excellent yields of the 1-phenyl-1-propene may be obtained by allowing the reaction mixture t o stand for 3-4 hours at 0". 0 The reaction mixture cooled to 0" was agitated for one hour. About 40% of triphenylethylene and 40% of polymer were obtained, in addition t o the triphenylacrylic acid. a
GRIGNARD REAGENTS AND ORGANIC HALIDES
295
presence of metallic halides. Various mixtures of Grignard reagents and organic halides were treated with carbon dioxide both in the presence and absence of metallic halides. The results (Table I) indicate that, in the absence of metallic halides, no radical interchange occurs? In this respect, the results here given are similar to those previously reported by Gilman and Jones (1). In the presence of cobaltous chloride, a radical interchange undoubtedly takes place, but this interchange is probably not the result of a simple metathetical reaction such as A or A'. The difficulties in the way of determining what does occur are considerable. In the presence of cobaltous chloride, the otherwise inert mixture of the Grignard reagent and the organic halide reacts very rapidly (9) even a t 0". In order to demonstrate any radical interchange, it was,therefore, necessary to keep the reaction mixture between 0" and -5" and to avoid excessive amounts of cobaltous chloride. In general, about 1% of cobaltous chloride gave the best results. The failure to demonstrate radical interchange when 25% of cobaltous chloride was used is due to the speed of the competing reactions initiated by the cobaltous chloride. The hypothesis of radical interchange helps to account for certain results previously obtained in this laboratory but not hitherto explained. For example, when n-butylmagnesium bromide is treated with phenyl bromide in the presence of cobaltous chloride, 3% of biphenyl is formed (10). It has been shown (9a) that, when phenylmagnesium bromide is treated with either butyl or phenyl bromide in the presence of cobaltous chloride, 70-90% of the phenyl Grignard reagent present is transformed into biphenyl. The 7-8% of benzoic acid formed when the mixture of n-butylmagnesium bromide, phenyl bromide, and cobaltous chloride is treated with carbon dioxide indicates a radical interchange of 7-8%, an amount which accounts nicely for the 3% of biphenyl found in the earlier experiments. When w-bromostyrene is treated with methylmagnesium bromide in the presence of one mole per cent of cobaltous chloride, there is no radical interchange ; when triphenyl bromoethylene is treated under similar conditions with the same reagents, radical interchange occurs to the extent of 32%. The divergence between these two results is due to a marked difference in reaction rates. The o-bromostyrene was treated with carbon dioxide after it had stood a t 0" for 10 minutes. By this time, the compound bad reacted to give 75% of 1pbenyl-l-propene, 8% of 1,4-diphenylbutadiene7and some tar. Little, if any, of the original organic halide was left. Whether the 1,4-diphenylbutadiene was formed by a radical interchange mechanism, or whether it was formed by the dimerization of the free radical (produced by removal of the bromine atom from the w-bromostyrene) has not yet been determined. Past experience (9) has shown that free phenyl radicals do not dimerize to biphenyl. Hence, it seems
* An exception to this statement is the ready radical interchange which takes place when w-bromophenylacetylene is treated with methylmagnesium bromide. I n this instance, treatment of the mixture with carbon dioxide gives mostly phenyl propiolic acid (Kharasch and Lambert, unpublished work). This result will be discussed in a later paper.
296
M.
6. KHARASCH AND C. F. FUCHS
probable that, in the system under discussion, the 1 ,Cdiphenylbutadiene is the end product of two successive reactions: H H
I
I
(a) Radical interchange to give CSHsC=CMgBr
H H
I
I
(b) Reaction of the CsHsC=CMgBr with cobaltous chloride (in the presence of an organic halide) t o give 1,4-diphenylbutadiene.
As already stated, radical interchange in the presence of cobaltous chloride is probably not a simple metathetical reaction. Provisionally, the following series of reactions is suggested as an explanation of what occurs in a mixture of butylmagnesium bromide, phenyl bromide, and cobaltous bromide. (a) C4HsMgBr (b) C4HBCoBr-+ (c) C4Hs. (d) CsH6Br -+e
(e) CsH6
I
a
+
-+
+ CoBrz -+ C4H9CoBr+MgBrz .CoBr + C4He.
+
C4H10 C4Hs .CoBr -+ CoBra
+ C~HK.
Polyphenyls and tar
GHsMgBr,
CaH6MgBr
+ C4Hs.
Phenylmagnesium bromide and an organic halide in the presence of cobaltous chloride yield biphenyl. The extent of the radical exchange, therefore, depends in a large measure upon the rates of the two competing reactions represented as (e). More work on the mechanism of radical interchange reactions is contemplated. EXPERIMENTAL PART
The experiments listed in Table I were conducted as follows. Except where contrary statements appear in the table, about 0.05 mole of Grignard reagent in 0.1 molar ethereal solution was used. To this solution (kept a t 0" to5"), onemole per cent of cobaltous chloride was added. This mixture was agitated, and an amount of alkyl halide equivalent (in moles) t o the amount of Grignard reagent was added. The entire mixture was kept at 0' t o 5" for 10 minutes and then treated with an excess of dry carbon dioxide. Then the entire mixture was treated with water. The water layer was separated, acidified with dilute sulfuric acid, and extracted several times with ether. The ether extracts were added t o the main ether solution. The aqueous solution was made up to volume, and its content of halide ion was determined. From this amount of halide ion, the amount of halide ion originally present in the Grignard reagent and metallic chloride was deducted. The difference corresponds t o the amount of halogen set free from the alkyl halide by the condensations catalyzed by the metallic halide. This difference, recalculated in terms of per cent of organic halide originally present, is given in the fourth column of the table. The ethereal solution was worked up for its content of organic acid in the usual manner. I n many instances, the amounts of the two acids (one derived from the original Grignard reagent, and the other derived from the organic halide) were both determined. The latter
GRLGNARD REAGENTS AND ORGANIC HALIDES
297
figure, recalculated as mole per cent of the organic halide originally present, is given in column five of the table. The former figure is not given since i t is regarded as unimportant. In the table, an asterisk over the number of the experiment indicates that a parallel reaction was run in the absence of any metallic halide. The only acid obtained in each such blank experiment was the one derived from the Grignard reagent originally present. SUMMARY
It has been shown that, in the presence of about one mole per cent of cobaltous chloride, radical interchange in certain systems of Grignard reagents and organic halides takes place, whereas no radical interchange in these systems occurs in the absence of such a catalyst. A mechanism for this “catalyzed” interchange is suggested. CHICAGO, ILL. REFERENCES (1) GILMAN AND JONES,J . A m . Chem. SOC., 61, 2840 (1929). (2) FISCHER, OAKWOOD, AND FUSON, J . A m . Chem. SOC.,62,5036 (1930). AND SHUSTER, Ann., 481, 106 (1930). (3) L~WENSTEIN (4) P R ~ V O SBull. T , SOC. chim., 49, 1372 (1936). (5) UMNOVA, J . Russ. Phys.-Chem. SOC.,46, 881 (1913);Chem. Zentr., 11, 1478 (1913). (6) URION,Compt. rend., 198, 1244 (1934). unpublished work. (7) KHARASCR, (8) WUYTS,Cornpt. rend., 199, 1317 (1934). (9) (a) KHARASCH AND FIELDS,J . A m . Chem. SOC., 63,2316 (1941);(b) KHARASCH, SAYLES, AND FIELDS,J . A m . Chem. SOC.,66, 481 (1944). (10) KHARASCH, LEWIS,AND REYNOLDS, J.Am. Chem. SOC.,66,498 (1943).
