June 5, 1956
PREPARATION AND
[CONTRIBUTION FROM
THE
REACTIONS OF BRIDGEHEAD MERCURIALS
DEPARTMENT O F CHEMISTRY, UNIVERSITY
OF
CALIFORNIA,
LOS
2597
ANCELES]
Mechanisms of Reaction of Organomercurials. 111. Preparation and Substitution Reactions of Bridgehead Mercurialsl BY S. WINSTEINAND T. G. TRAY LOR^ RECEIVEDNOVEMBER 11, 1955 The device of incorporating, as the site of substitution, the bridgehead of a bicyclo[2.2.l]heptane system, illuminating in connection with nucleophilic substitution, has been employed in the study of the behavior of organomercurials. 4Camphylmercuric chloride, bromide, iodide and nitrate, as well as dicamphylmercury, have been prepared, and substitution reactions of some of these materials have been studied. The prohibitive factor against generation of a cationic center a t the bicyclo[2.2.l]heptyl bridgehead, resulting from inefficient use of the 2s orbital, is not present in the case of the free radical. Thus, a number of reactions involving bicyclo[2.2.l]heptyl bridgehead radicals are known to proceed well. I n the present work, two apparently radical reactions of organomercurials proceeded normally with the 4-camphylmercury derivatives. One reaction involved the conversion of 4-camphylmercuric chloride to dicamphylmercury with sodium stannite solution. The other involved the conversion of 4-camphylmercuric iodide to 4-iodocamphane by iodine in dioxane. This reaction, strikingly oxygen-retarded, proceeded a t a rate approximately equal t o that for n-butylmercuric iodide. In contrast with the inertness of the bicyclo[2.2.1] heptyl bridgehead position to nucleophilic substitution is the relative ease of electrophilic substitution with the 4-camphylmercury derivatives. The investigated electrophilic substitution reactions included the reaction between di-4-camphylmercury and mercuric chloride, neutral first-order and acidic second-order acetolysis of dicamphylmercury, and the second order reaction between 4-camphylmercuric iodide and triiodide ion in slightly aqueous dioxane. All of the electrophilic substitutions of the 4-camphylmercury derivatives necessarily proceed with retention of configuration. The bridgehead derivatives are not especially unreactive, occupying an intermediate position in reactivity between the neophyl and butyl analogs. Thus, there is no indication that the brideghead derivatives are forced to react by a mechanism leading t o retention simplv because another inherently much more preferable one is excluded by the bridgehead restrict ion.
The unique situation of the bicyclo [2.2. llheptyl Preparations.-The bridgehead chloride 4-chlorobridgehead carbon atom completely precludes in- ~ a t n p ' h a n e * ~ was prepared from dl-camphor by (11) (I) very satisversion of configuration and makes extremely way of the 2,4-dichloro~amphane~ difficult the generation of a cationic center in sub- factorily by the method of Doering and Schoene~ ~ 4-chlorocamphane (11) was constitution reactions a t the bridgehead. For these ~ a l d t .The reasons, bridgehead derivatives have proved illu- verted to 4-camphyllithium (IV) by a method minating in connection with nucleophilic substitu- similar to that described by D ~ e r i n g . ~ When the tion in the original elegant studies of Bartlett3 4-camphyllithium was treated with excess mercuric chloride, 4-camphylmercuric chloride (VII), a highand the more recent ones of D ~ e r i n g . ~ J The device of incorporating as the seat of sub- melting stable material, was obtained in good yield. stitution the bridgehead of a bicyclo [2.2.l]heptane When half a mole of mercuric chloride was emsystem should also be effective in studying electro- ployed, di-4-camphylmercury (VIII) was obtained, philic substitution. I n fact, Hughes and Ingold6 although the yield was not good, perhaps for soluhave used the supposed inertness of bridgehead bility reasons. The 4-camphylmercuric chloride carbon in electrophilic substitution as the basis of a c1 c1 tentative suggestion that S,2 displacement on saturated carbon normally proceeds with inversion Xa, EtOH ,',/ of configuration. These authors judged the bridge- R H ---+ iT1=RCl head position to be relatively inert on the basis of \I/ available information on liquid phase nitration, a I11 I I reaction which they, a t that time, apparently assumed to be an electrophilic substitution. In the course of our study of organ~mercurials~ several 4-camphylmercury derivatives have been KCOOH prepared, and they have been subjected, not only v to electrophilic substitution reactions, but also to I \ free radical reactions. This work is reported in the present article.
-
(1) Part of the material of this paper was reported a t the Organic Reaction Mechanisms Conference, Northwestern University, Evanston, Ill., August 31, 1950. ( 2 ) U. S. Rubber Company Predoctoral Fellow, 1961-1952. (3) (a) P. D. Bartlett and L. H. K n o x , THIS JOURNAL, 61, 3184 (1939); (b) P. D. Bartlett and S. G. Cohen, i b i d . , 63, 1184 (1940); (c) P. D. Bartlett and E . S. Lewis, i b i d . , 73, 1005 (1950). (4) (a) W. von E . Doering and E. F. Schoenewaldt, i b i d . , 7 8 , 2333 (1951); (b) W, von E. Doering, M . Levitz, A. Sayigh, M. Sprecher and W. P. Whelan, Jr., i b i d . , 75, 1008 (1953). (5) (a) W. von E. Doering, private communication; (b) W. von E. Doering, page 3 5 M of Abstracts, 123rd Meeting of the American Chemical Society, Los Angeles, Calif., March 15-19, 1953. (6) E . D. Hughes and C. K. Ingold, J . Chem. Soc., 255 (1935). (7) (a) S . Winstein, T. G. Traylor and C. S. Garner, THISJOURNAL, 77, 3741 (1955); (b) S. Winstein and T. G. Traylor, i b i d . , 77, 3747 (1955).
RHgI IX
KI f-
SaOEt
r\'a,Sn( OH)c
RHgCl
H
VI1
NaCl
RHgS03 XI
~
RHgBr X
R
+ I c ~
AcOH
Hg~
I
R VI11
RH I11
( 8 ) (a) H. Meerwein and R. Wortman, A n n . , 4S5, 190 (1823); (b)
J. Houben and E. Pfankuch, ibid., 501, 219 (1933).
S. WINSTEINAND T. G. TRAYLOR
2598
(VII) could be converted conveniently by metathesis to the bromide X, iodide IX and nitrate XI. Alternatively, the bromide X was derived from 4camphyllithiurn (IV) and mercuric bromide. Radical Reactions at the Bridgehead. Reduction of 4-Camphylmercuric Chloride VI1 with Sodium Stannite.-Although evidence on the mechaiiism of formation of dialkylmercury from alkylmercuric halide and sodium stannite is very scanty, the indications are that this reaction involves the alkyl free r a d i ~ a l . ~ Treatment of 4-camphylmercuric chloride (VII) with aqueous sodium stannite was a t first quite unsuccessful for production of di4-camphylmercury (VIII) but this failure appeared to be due to extreme insolubility of 4-camphylmercuric chloride (VII) in aqueous base. When the suspension of 4-camphylmercuric chloride in sodium stannite solution was stirred for a time with a high speed stirrer, conversion to di-4-camphylmercury (YIII) did take place. Reaction of 4-Camphylmercuric Iodide (IX) with Iodine.--A thorough study by Keller'O of the reaction of alkylmercuric iodides with iodine in dioxane showed this reaction to be free radical in nature. The rate of this reaction is very sensitive to light and peroxides, and it is very strongly retarded by oxygen. Only when the reaction mixture was in equilibrium with an atmosphere of air or oxygen was the reaction rate reduced sufficiently to be conveniently measured. Although the rates were somewhat erratic, they were usually reproducible for the first portion of the reaction. The study showed the reaction rate to be roughly second order in iodine and nearly independent of alkylmercuric iodide concentration. Reaction rate was quite insensitive t u changes in structure of the alkylmercuric iodide and approximately inversely proportional to oxygen concentration. The observations were consistent with a chain reaction involving attack of iodine atoms on mercury to generate alkyl radicals and reaction of the latter with iodine as in equations 1 and 2.
VOl. 78
Using the technique developed by Keller,'O several rate runs were made on the radical reaction of iodine with 4-camphylmercuric iodide (IX) in dry, purified, peroxide-free dioxane. These rates were even more erratic than those of Keller. A sample run is illustrated in Table I. However, even the slowest runs a t 40' in air-saturated dioxane gave a second-order rate constant of 1.4 X loe3 set.-' M - l , approximately equal to the value observed'O for n-butylmercuric iodide, namely, set.-' M-l. 1.5-2 X TABLE I REACTIONO F 4-CAMPHYLMERCURIC IODIDE (Ix) IODINE IN AIR-SATURATED DIOXANE AT 40.0" 0.02407 M RHgI, 0.05022 &I I1 Time, sec.
0 845
1, A - G 2,805 :I,720 4,500 5,135 6,540 10,000 15,000
Thiosulfate, ml.a
5. 02,5 4 765 4 690 4 424 4 130 3 780 2 401 2 703 2,697 2.680
104
[ I I l , '$l
0.04962 ,04705 .0463 I .04368 .04078 ,03732 .03358 .02671 . 02663c . 02646d
WITH
k*,t
sec. - 1 d l
-.
13.0 8.8 9.8 11.7 14.8 1s.7
Mean 13 Volume of 0.1003 N thiosulfate solution for a 5.0-ml. aliquot. Second-order rate constant defined by the expression. - d [ I ~ l / d t = k 2 [ I 2 I 2 . 98%ccompletion. 99.3% completion. a
The product of the radical reaction of 4-camphylmercuric iodide (IX) with iodine was 4-iodocamphane (VI), isolated in high yield. The isolated material was identical with that prepared by treatment of 4-camphyllithium (IV) with iodine. Electrophilic Substitution at the Bridgehead. Reaction of 4-Camphylmercuric Iodide (IX) with Triiodide Ion.-An extensive study by Ke1ler'~'O of the reaction of alkylmercuric iodides with iodine I . + RHgI +R . $- HgI2 (1) in the presence of iodide ion in aqueous dioxane has R. I? +RI I. revealed an ionic mechanism for the substitution. (2) LTith butylmercuric iodide, l.l0 the strong oxygen Excellent second-order rate constants, first order in retardation of its reaction with iodine was strik- triiodide ion and first order in the alkylmercuric ingly demonstrated by the following procedure.1c iodide, were obtained for the reaction of typical A dioxane solution, 0.025 M in iodine and 0 05 ill organomercuric iodides. In general, under the in n-butylmercuric iodide, when saturated with air, ionic conditions the radical reaction did not conrequired ca. 9000 seconds for 50% reaction. How- tribute appreciably. However, with neophylmcrever, when oxygen was removed by successive curic iodide (2-methyl-2-phenyl-1-propylmercuric degassing of the separate iodine and mercurial iodide) the ionic reaction is slow enough that with solutions in a two-legged flask, and then the solu- 0.05 Ai' reactants the radical reaction accounts for tions were mixed, the iodine was completely con- an appreciable amount of the total reaction even sumed in ca. 1s seconds. U'hen this procedure was in oxygen-saturated solutions. This difticulty carried out with 0.05 i l l 4-caniphylmercuric could be overcome by reducing the iodine conceniodide (IX) and 0.025 M iodine, the iodine was tration and increasing the mercurial concentration. completely consumed in ca. 15 seconds. In air- Because the radical reaction is approximately saturated solution, 4 to 6 hours was required to second order in iodine and zero order in alkylmerconsume the iodine. Thus, the bridgehead organo- curic iodide, reducing the iodine concentration and mercurial IX is analogous to butylmercuric iodide increasing the alkylmercuric iodide concentration, and other mercurials in the clearly radic'tl nature of so as to keep the product constant, has the effect of reducing the importance of the radical reaction. the reaction with iodine. By taking the rate in solutions initially 0.01 I I f in (9) (a) T G Tmylor, Thesis, U. C. L A , 1952, (b) reference i a iodine and 0.2 11f in neophylmercuric iodide, good footnote 27. second-order constants were obtained. lo 110) J Keller, 1 h e s i b , U C L A , lrJ.18.
+
+
June 5, 1956
PREPARATION AND
I n the present work, the rates of reaction of 4camphylmercuric iodide (IX) with iodine and excess iodide ion have been measured by the same method and under nearly the same conditions as those employed by Keller Io with neophylmercuric iodide. Because of the slight solubility of 4-camphylmercuric iodide (IX) the solvent in the present work contained 5y0 water by volume instead of 10% as used by Keller. Also, i t was necessary to reduce the lithium iodide concentration to 0.125 M in order to maintain a single liquid phase. The kinetic behavior of 4-camphylmercuric iodide (IX) proved to be similar to that of neophylmercuric iodide. With 0.05 M iodine and 0.025 M 4-camphylmercuric iodide (IX), second-order rate constants, kz, calculated on the basis of equation 3, showed definite drifts. Also, the reaction was still about one-fifth as fast in the absence of iodide ion as in -d[RHgI] = ke[RHgIl [I&] dt
2399
REACTIONS O F BRIDGEHEAD AIERCURIALS
(3)
the presence of 0.125 M iodide. Apparently, the radical reaction complicates the kinetics of the reaction of triiodide ion with 4-camphylmercuric iodide (IX). In increasing the ratio of mercurial to iodine to render the radical reaction unimportant, the relatively low solubility of 4-cainphylmercuric iodide (IX) in 95% dioxane (cu. 0.05 M ) was a difficulty. This made i t necessary to employ initial iodine concentrations below 0.005 M , rendering the usual titration methods with visual end-points too inaccurate. The reactions could be followed satisfactorily, however, by an electrometric determination of the end-point in the thiosulfate titration of the iodine. At the low iodine concentrations, satisfactory second-order behavior was displayed by 4-camphylmercuric iodide (IX) in the reaction with triiodide ion. I n Table I1 is illustrated one of the runs a t 0.0036 M iodine, and the results of three runs are summarized in Table 111. These results show the second-order rate constants insensitive to a twofold change of iodine concentration and to the change in lithium iodide concentration from 0.125 to 0.05 M .
TABLE I11 RATESO F REACTION O F 4-CAMPHYLMERCURIC IODIDE(IX) WITH TRIIODIDE IONIN 95% DIOXANE AT 55.0"
SUMMARY O F
y03p 3.36 3.48 3.89
[LiIl, 10*M
[Izl, 10%M
12.5 12.5 5.00
0.357 ,218 ,445
103 kz, sec. - 1 .Vf
-1
1.27 f 0.09 1.5 f .5 1 . 5 3 f .14
As in the case of the reaction under radical conditions, the product of the action of triiodide ion on 4-camphylmercuric iodide (IX), under largely ionic conditions, was 4-iodocamphane (VI), isolated in good yield. Acetolysis of Di-Ccamphylmercury (VIII).-Tke acetolysis of di-4-camphylmercury (VIII) was studied, as were the several other dialkylmercuries reported in the previous article.7b The alkylmercuric acetate was titrated with hydrogen bromide in acetic acid using hydroquinone to decrease endpoint drift. This drift was somewhat of a problem, although not as acute as with di-s-butylmercury or diphenylmercury . At 50 and 75', first-order rate constants of acetolysis of di-4-camphylmercury (VIII) showed no definite drift. The data for one run a t 75' are given in Table IV, and several runs are summarized in Table V, which lists also the AH* and A S * of the reaction. Isolation of the product of acetolysis after 10 reaction half-lives by treatment of an aliquot with excess aqueous lithium chloride gave rise to 4-camphylmercuric chloride (VII). TABLE IV ACETOLYSIS O F 0.0271 h ! DI-4-CAMPHYLMERCURY (\'III) 75.0'
AT
Time, sec.
HBr, ml.a
[RzHgl, M
106 k , sec. - 1
0 3,900 8,100 11,915 18,300 23,835 29,460 42,240 52,830 467,940
0.247 .530 .790 1,090 1.315 1.500 1.660 1.860 1.988 2.322*
0.02428 ,02101 ,01800 ,01453 ,01193 ,00978 ,00793 ,00562 .00414
3.7'1 3.70 4.31 3.88 3.82 3.80 3.46 3.35
TABLE I1 Mean 3.75 f 0.20 REACTIONAT 55.0' O F 0.0336 ?M 4-CAMPHYLMERCURIC a Volume of 0.05000 M hydrogen bromide per 4.321-m1. IODIDE (IX) WITH 0.00357 M IODINE IN 95% DIOXANE, aliquot. b99% completion; a trace of metallic mercury observed. 0.125 M IN LITHIUMIODIDE' 103 ki; TABLE T' Time, Thiosulfate, [?$$I* sec. M --, sec. ml. b [ I ~ ]103 , M RATES O F ACETOLYSIS O F DI-4-CAMPHYLMERCURY (1-111) Temp., 'C. [RzHgl, 102 M k, sec.-1 0 11.264 3,500 3.363 3,720 9.905 3.077 3.321 1.04 25.0" 5 . 2 x 10-7 7,500 7.921 2.461 3.2.59 1.42 49.6b 2.71 (5.1 f0.5) X 8,460 7.817 2.429 3.256 1.30 75.0 2.71 (3.75 i .20) x 10-6 15,630 6.073 3.202 1.21 1.887 75.0 1.06 (3.7 f . 4 ) x 10-6 20,450 4.998 1.553 3.168 1.22 25.9 1.7SC (1.6 .3) x 10-3d 21,275 4.438 1.379 3.151 1.35 Extrapolated from the data a t the other temperatures. 33,590 2.942 0.914 3.104 1.25 b A H * = 17 kcal./mole; A.3* = -12 e.u. cO.0447 M HClQ. Second-order rate constant; see.-' M-I. 57,915 0.908 0.282 3.041 1.39 Mean 1.27 If 0 . 0 9 As with d i n e ~ p h y l m e r c u r y ,inclusion ~~ of perOxygen was bubbled a t the rate of 3 ml. per minute chloric acid in the glacial acetic acid gave a much through dioxane a t 55' and then through the reaction mixture. * Volume of 0.001516 Nsodium thiosulfate per 4.880- enhanced rate of solvolysis of the di-4-camphylmercury (VIII). The xcond-order rate constant obml. aliquot.
*
2600
S. WINSTEINAND T. G. TRAYLOR
served with 0.0447 M perchloric acid at 25.9", recorded in Table V, was 1.6 X set.-' M-l. Comparison with the first order rate constant extrapolated to 23" (Table V) shows that the secondorder rate constant exceeds the first-order one by a factor of ca. 3000. Reaction of Di-4-camphylmercury (VIII) with Mercuric Chloride.-Di-4-camphylmercury (VIII) and mercuric chloride, both very soluble in ether, react readily in this solvent a t 25' to give a high yield of 4 camphylmercuric chloride (VII). X1though no measurements of rate were carried out, the reaction was obviously not slow, since a large amount of the product had already crystallized out after ca. 6 hours. Reduction of 4-Camphylmercuric Chloride with Lithium Aluminum Hydride.-Alkylmercuric chlorides are reduced to hydrocarbon by lithium aluminum hydride. The mechanism of the reaction is riot clear, but there is some indication that the carbanion is an intermediateaga Application of this reaction to the bridgehead mercurial I'II gave camphane (111) in relatively low yield, at least partly because of loss due to volatility. Discussion Regarding ease of generation of cation, radical and anion centers a t the bridgehead position of the bicyclo [2.2.1Iheptyl skeleton, the most important consideration appears to be promotion energy associated with inefficient use of the 2s orbital in orbital hybridization about the bridgehead carbon atom. Since the change from s p 2 hybridization a t an ordinary carbonium ion center to s p 3 corresponds to promotion of one-fourth of a 2s electron to 2 p , Kimball" estimates that a planar cation with s p s hybridization is more stable than a pyramidal cation with s p 3 hybridization by 21 kcal./mole. Considering the great strain associated with any approach to planarity and thus return of promotion energy, the extreme difficulty of generation of a cationic center a t the bicyclo[3.2.1Iheptyl bridgehead p o s i t i ~ n ~ - ~
