4912
4. STREITWIESER, [CONTRIRUTION FROM
THE
JR., A N D
\.-01.
J. R. KOLFE, JR.
s1
DEPARTMENT O F CHEMISTRY, UNIVERSITY OF CALIFORNIA]
Stereochemistry of the Primary Carbon. XI. Ethanolysis of Optically Active Benzyl- a-d p-Tolu enesulf onat e BY A. STREITWIESER, JR.,
AND
J. R. WOLFE,J R . ~
RECEIVED-4PRIL 3, 1959 The reaction of optically active benzyl-a-d tosylate with alcoholic sodium ethoxide apparently goes with complete inversion of configuration. The preparation of ethyl benzyl-a-d ether by the reaction of the alcohol with silver oxide and ethyl iodide or with potassium t-butoxide and ethyl iodide involves some racemization. Solvolysis of benzyl-a-d tosylate in absolute ethanol goes with comdete inversion of confiauration; ethanolysis and hydrolysis in SO% aqueous ethanol iiivolve a t most a few per cent. of racemization.
-
As part of a study of the stereochemistry of of an ionizable iodide which may have been benzyl ethanolysis and acetolysis of some primary and iodide indicates the possibility of racemizing side secondary sulfonates, the simple benzyl system was reactions. From the results summarized in Table of interest because it combines the low steric I we estimate that about 14y0 racemization ochindrance to displacement of a primary system with curred in this preparation. Hence this procedure a carbonium ion stability similar to that of secon- cannot be used for the stereospecific preparation of dary carbonium ions.3 I n this paper we report the ethers without circumspection. The highest roresults of our study of the stereochemistry of tation for the ether was obtained by the reaction ethanolysis of optically active benzyl-a-d tosylate of benzyl-a-d tosylate with alcoholic sodium which was made possible by the recent preparation ethoxide. The reaction with ethoxide ion is unof optically active benzyl-a-d alcoh01.~ doubtedly a direct displacement; since the competThe benzyl-a-d alcohol used throughout this ing solvolysis has been shown also to involve little study had a 3 0 ~-3.006 =t0.004" ( I 4).5 Prepara- or no racemization (vide infra), this rotation, tion of the tosylate by reaction of the alcohol with [ C X ~ D 0.098 j= 0.004", is taken to be of the same tosyl chloride and alkali hydroxide6 or sodium relative optical purity as the starting alcohol and of hydride' was undesirable because of the possibility opposite configuration. The reaction of benzylof racemization in these reactions. However, the a-d alcohol in t-butyl alcohol solution with potasprocedure used by Edge11 and PartsBfor the prepa- sium t-butoxide and ethyl iodide gave the ethyl ration of methyl tosylate was adapted to our prepa- ether with a slightly lower rotation.1° Final purification of these ethers included reration. This procedure, the reaction of benzyla-d alcohol with tosyl chloride in pyridine a t -4O", action with lithium aluminum hydride which gave 50yo yields of once recrystallized benzyl- generated a few per cent. of benzyl alcohol una-d tosylate often contaminated with some un- doubtedly by reduction of peroxide formed by air reacted tosyl chloride. Because of the instability oxidation. Indeed, the product from the potasof the benzyl tosylate no attempts a t further sium t-butoxide reaction was found after a year of purification were made. The results to follow storage to be somewhat decomposed and to have demonstrate that 110 racemization of the tosylate lost several per cent. of its optical activity undoubtoccurred during this preparation and that the edly because of reactions induced by air oxidation. presence of some tosyl chloride could be tolerated. The solvolysis of benzyl-a-d tosylate about 0.15 Several procedures have been used for the stereospecific conversion of alcohols to ethers. Mislowg A I in absolute ethanol for 5-6 half-lives a t 23' gave has demonstrated that in some cases the reaction a product which was found to contain chlorine. of an alcohol with silver oxide and ethyl bromide or It seems likely that ethanolysis of the contaminatiodide involves no racemization. Applied to ing tosyl chloride produces chloride ion which reacts benzyl-a-d alcohol this procedure gave ether having with benzyl-a-d tosylate chloride a t a rate conia lower rotation than that from other preparations. parable to ethanolysis of the tosylate. In both The presence in the crude product of this reaction runs the optical activity of the mixture and the chlorine analysis was used to estimate the rotation (I) This research was supported in part b y a grant from t h e Peof benzyl-a-d chloride as [ f f ] D 0.51 =t 0.07" and troleum Research F u n d administered by t h e American Chemical 0.67 j= 0.02", respectively. Since this product is Society. Grateful acknowledgment is herehy made t o t h e donors of the fund. This paper v a s taken in part from the P h . D . dissertation undoubtedly of inverted configuration, alcohol and of J. R . TVolfe (1957), University of California. and was presented in chloride of the same sign of rotation have the same p a r t a t the 7th Conference on Reaction LIechanisms, 'IJniversity of configuration. Indeed, alcohol, acetate, bromide, Chicago, Ill., September, 1938. chloride and ethyl ether of the same sign of rotation (2) 3fonsanto Fellow, 1956-1957. ( 3 ) A. Streitwieser, Jr., Chem. Reus., 66, 571 (1956). have the same configuration. The relative ro(4) A . Streitwieser, Jr., and J . R . Wolie, Jr., Txrrs J O I T R N A I . , 79, 909 tations of various benzyl derivatives are s u n (1967). ( 5 ) A . Streitmieser, J r . . J. R . Wolie, Jr., and U'. D. Schaeffer, marized in Table 11. It is interesting to note that the rotations of the bromide and chloride are of Teirahedvon, in press (1959). (6) F. L. Hahn and H . Walter, B e y . , 54B,1531 (1921); H. Gilman comparable magnitude.
+
and N . J . Beaber, THISJ O U R N A L , 47,518 (1925); 2 . Foldi, B e y . , 60B, 656 (1927); F. Drahowzahl and D. Klamann, Monnfsh.. 82, 4 5 2 (1951). (7) J. Kochi and G. S. Hammond, T H I S JOURNAL, 7 5 , 3443 (1953). (8) W F. Edgel! and L. Parts, i b X , 7 7 , 4899 (1965). (9) K . Mislow, ibid., 73, 4043 (1951).
(10) T h e rotation with t h e mercury green line is actuaily higher than t h a t of the "standard." However, the dispersion ratio, a m / OLD = 1.32, for this case is much higher t h a n t h a t of any other prepnration. We consider t h e rotation with t h e sodium D line t o be more accurate and t h a t the 5461 rotation in this case is suspect.
a.
4913
ETHANOLYSIS OF BENZYL-&p-TOLUENESULFONATE
Sept. 20, 1959
TABLE I OPTICALACTIVITYO F PREPARATIONS OF BENZYL-a-d ETHYLETHER Benzyl-a-d ethyl etherReaction
+ + +
Temp., "C.
+
-0.086
Room Reflux Room 25 25
ROH t-BuOK Et1 ROH Et1 Ag,O ROTS NaOEt, E t O H ROTs, E t O H ROTs, 80% E t O H
+
( I 1) =t0.001'
a ~ i ( Ii 1) ~
-0.113 f 0.002' - ,092 =t ,002 .I08 ,005 . l o 9 f ,007 . 0 9 5 i ,010
- .os1 f
+ + +
TABLE I1 RELATIVE ROTATIONS AND CONFIGURATIONS BENZYL-&DERIVATIVES CsHaCHDX X
aDa
aD(l1)
OF
,002 ,004 .002 .OS6 f .004
+ + +
,093 .095 =t
SOME
[alD"
OH -0.752" -0.7150b - ,182 - ,170" OCOCHa OC&s - .093 - .098d c1 - ,gd," Br - .9 - .6" OCOC~,H~COOH-O .22."f Signs of rotations for same relative configuration. * Ref. 5 . c Ref. 4. This paper. e In benzyl-a-d ethyl ether. f In acetone.
+
The ethanolysis product was purified by reaction with lithium aluminum hydride to remove the benzyl chloride then by a treatment with phthalic anhydride and pyridine to remove alcohol; comparison of the rotations with those of the "standars" ether a t the sodium D line and mercury 5641 A. line showed the ethanolysis to involve 102 =t5% and 100 =t 7y0net inversion of configuration, respectively. The contamination by benzyl-a-d chloride was not expected to affect these results since this compound solvolyzes less than 1/1000 as fast as the tosylate.ll Benzyl-a-d tosylate was allowed to solvolyze in 807, aqueous ethanol for about 7 half-lives a t 25'. N o benzyl chloride was formed in this reaction undoubtedly because displacement by chloride ion does not compete with this faster solvolysis. The ethyl ether produced in the solvolysis showed 93 rt 6% and 87 =t 10% inversion a t the sodium D and mercury 5461 A. lines, respectively. The few per cent. of racemization is apparently real although the amount found is hardly greater than the estimated experimental error. The benzyla-d alcohol simultaneously produced in the solvolysis was isolated as the hydrogen phthalate and the rotation was compared with that of hydrogen phthalate prepared directly from the alcohol. The hydrolysis went with 96 f 5% and 101 =tt4y0inversion a t the sodium D and mercury 5461 A. lines, respectively. Hence there is no evidence for racemization in the hydrolysis reaction. The complete inversion found in the present solvolysis in ethanol may be compared with the complete inversion also found for ethanolysis of secondary alkyl sulfonates.12 The slightly greater racemization found for ethanolysis of benzyl tosylate compared to 2-butyl brosylate in 80% aqueous ethanol, if real, indicates that the benzyl cation is somewhat more stable than a secondary (11) S. Winstein, E. Grunwald and H . W. Jones, THISJOURNAL, 75, 2700 (1951). (12) A. Streitwiesrr, Jr., and A. C. Waiss, Jr., unpublished results.
*
am/aD
1 . 3 2 f 0.03 1 . 1 4 f .03 1 . 1 7 =k .06 1 15 =t .06 1.10 i .I1
alkyl carbonium ion. The addition of an aalkyl group to the benzylic system causes a large increase in the amount of racemization; a-phenethyl tosylate solvolyzes with l7yOnet inversion in e t h a n ~ l ,whereas ~ . ~ ~ the chloride gives about 27y0 net i n v e r ~ i o n . ~The ~ ' ~ addition of a second alkyl group apparently causes still more racemization (methanolysis of phenylmethylethylcarbinyl hydrogen phthalate gives about 10% net inversion of configurationlj). Addition of an a-aryl group apparently results in complete racemization (meth anolysis of optically active phenyl-p-tolylcarbinyl hydrogen phthalate gives a racemic methyl ether; however, the optical stability of the product to the reaction conditions was not determinedI6). The stereochemistry of a range of structural types may now be summarized as in Table 111. The results TABLE I11
STEREOCHEMISTRY OF ETHANOLYSIS, PhCRlRzX Ri
R,
h'et % inversion
H H 100" R H 17-27b R R -loc Ar H OC Ar R Od Ar Ar Od a For X =OTs; probably also true for X = halogen or esters. For X = For X = OTs and C1, respectively. hydrogen phthalate in methanol. .%ssumed.
N
N
seem to depend almost wholly on carbonium ion stability and little or not a t all on the nature (;.e., primary, secondary or tertiary) of the reacting center.
Experimental Benzyl-a-d Alcohol and Benzyl-a-d p-Toluenesulfonate .The preparation of the optically active compounds used in this research has been described previously.6 Ethyl Benzyl-a-d Ether. Silver Oxide Method.-A mix; ture of 10 ml. (0.1 mole) of benzyl-a-d alcohol, C Y ~ O D -3.006 ( I 4), 24 g. (0.10 mole) of freshly prepared dry silver oxide" and 100 ml. (1.31 moles) of ethyl iodide was stirred for 3 days with daily additions of a further total of 48 g. of silver oxide and 200 ml. of ethyl iodide. iifter refluxing for 48 hours the mixture was filtered and distilled to yield a crude product which was contaminated with about 3y0 of benzyla-d alcohol (infrared spectrum). The alcohol was removed by treatment with pyridine and phthalic anhydride. Distillation gave 5.4 ml. of colorless liquid, b.p. 83-84' (24 mm.), which turned a light tan color on standing for several days. This product was treated with 5 g. of lithium aluminum hydride in ether at room temperature and was recovered in the usual manner to yield 4.5 ml. of benzyl-a-d ethyl ether contaminated with a small amount of benzyl alcohol. This (13) J. Kenyon, H. Phillips and R . M. H . Taylor, J . Chem. Soc., 173 (1933). (14) E. D. Hughes, C. K. Ingold and A. D. Scott, {bid., 1201 (1937). ( 1 5 ) H . H. Zeiss, THISJOURNAL, 76, 3154 (1953). (16) A. G. Davies, J. Kenyon, B. J. Lyons and T. A . Rohan, J. Chem. Soc., 3474 (1954). (17) H. Rapoport, J. G r g . Chem., lS, 714 (1948).
4014
A. STREITWIESER, JR., AND J. R. WOLFE,JR.
material had a Z 5-0.322 ~ f 0.009' ( I 4) and a2%81 -0.382 f 0.005' ( I 4 ) . After a second treatment with pyridine and phthalic anhydride, 3.1 ml. of ether was recovered, b . 81-85' (25 mm.), having a 3 0 D -0.161 k 0.004' and aaojm -0.183 f 0.004' ( I 2) and 7 ~ ~ 5 .1.4900. 5 ~ The infrared spectrum was identical t o that of benzyl-a-d ethyl ether prepared by other methods. A similar reaction of ordinary benzyl alcohol and ethyl iodide with silver oxide which has been stirred in the dark for a month resulted in the codistillation of a small amount of iodine with the product (identified by odor and color). The iodine was removed by washing the distillate with aqueous sodium thiosulfate. Redistillation of the colorless organic material gave a colorless product which gave a yellow-white precipitate with alcoholic silver nitrate which turned t o a light tan color on standing. This experiment indicates the presence of an ionizable iodide, possibly benzyl-a-d iodide. Potassium &Butoxide Method.-This method was conceived on the presumption that benzyl alcohol is a significantly stronger acid than t-butyl alcohol. T o a solution of potassium t-butoxide prepared under nitrogen from 350 ml. of dry t-butyl alcohol and 8 g. (0.2 g. atom) of potassium was added 10 ml. (0.1 mole) of benzyl-a-d alcohol and 27 ml. (0.35 mole) of ethyl iodide. After a few minutes the solutio11 became milky due t o the precipitation of potassium iodide. After stirring for 24 hours and dilutioti with water, the mixture was extracted with ether. Distillation of the washed and dried extract gave 10.5 ml. of benzyl-a-d ethyl ether contaminated with about 270 of benzyl-a-d alcohol. After treatment with pyridine and phthalic anhydride, 7.5 ml. of benzyl-a-d ethyl ether was recovered, ,b. 83.584.5" (23~ =k 0.003 , aPB5m-0.452 f 23 mm.), having a Z 6-0.344 0.008" ( I 4) and ~ z ~ 1.4909. ~ . ~ D The infrared spectrum was identical with that of benzyl-a-d ethyl ether of other preparations. After storage for a year the rotations had dropped about 7yoand the infrared spectrum showed additional bands. Sodium Ethoxide Displacement .-To a solution of sodium ethoxide prepared from 23 g. (1.0 g. atom) of sodium and 400 ml. of dry ethanol was added 12.4 g. (0.047 mole) of optically active benzyl-a-d tosylate a t room temperature. After stirring for 19 hours an additional 3 g. (0.01 mole) of benzyl-a-d tosylate obtained as a second crop of the above preparation was added and the reaction mixture was stirred for an additional 5 hours. The mixture was diluted with water and extracted with ether. Distillation of the washed and dried ether extract gave 3.6 ml. of benzyl-a-d ethyl ~ f 0.004", a Z 5 5 4 6 1 0.249 f 0.004' ( I 2). ether, a Z 50.179 After treatment of this material with lithium aluminum hydride and then pyridine and phthalic anhydride, 1.0 ml. was recovered having a Z 9 D0.139 +z 0.006", a Z B 5 4 6 1 0.163 =I= 0.007 ( I 1.5), ~ 2 5 . 51,4900. ~ The infrared spectrum was identical with that of benzyl-a-d ethyl ether prepared by other methods. Solvolysis of Benzyl-a-d Tosylate in Anhydrous Ethano1.Two runs were made. I n the first run, 13.6 g. (0.52 mole) of optically active benzyl-a-d tosylate was disso1v:d in 350 ml. of dry ethanol previously thermostated at 25 After the solution was maintained at 25" for 18 hours (about 5 half-lives) it was poured into 1.5 1. of water and the resulting mixture was extracted with ether. Distillation of the washed and dried extract gave 3.7 ml. of colorless liquid, b. 85-86.5" (24-25 mm.), a 2 1 ~0.256 f 0.005', aZ1546L0.308 +z 0.013' ( I
.
v O i . si
2). Redistillation of the product gave two fractions each having &*D 0.126 rt 0.004' ( I 1). Elementary analysis showed 1.78y0chlorine. The combined product was treated with 5 g. of lithium aluminum hydride; 3.2 ml. of colorless ~ + liquid was recovered, b. 84-87' (26-27 mm.), a Z 50.175 0.004", Cyz5461 0.215 zk 0.005' ( I 2). The infrared spectrum showed the presence of about 2% of benzyl alcohol which was not present prior to the lithium aluminum hydride treatment. This alcohol presumably arose from reduction of peroxide which formed in the benzyl-a-d ethyl ether by air oxidation. The product was heated on a steam-bath for 6-7 hours with 10 ml. of dry pyridine, 7.5 g. of recrystallized phthalic anhydride and 10 ml. of dry benzene. This reaction mixture was poured into aqueous sodium carbonate and the resulting mixture was extracted with ether. Distillation gave the purified solvolysis product. The solvolysis was repeated as above with a second batch of benzyl-a-d tosylate for 25.8 hours (about 6 half-lpes). There was obtained 3.6 ml. of product, b. 81.5-82 (2-1 mm.), a 2 5 ~0.365 zt 0.003' ( I 2). Elementary analysis showed 3.6770 chlorine. This product was treated with lithium aluminum hydride and then pyridine and phthalic anhydride as above. The products of the two solvolyses were combined and redistilled t o yield 3.1 nil. of colorless liquid, b. 87-88' (27 mm.), a 2 7 ~0.189 & 0.004", a Z 7 j 4 ~ ~ 0.217 f 0.013' ( I 2), ~ z ~ 1.4899; ~ . ~ D the infrared spectruni was identical with that of benzyl-a-d ethyl ether synthesized by other methods. Solvolysis of Benzyl-a-d Tosylate in 80% Aqueous Ethanol.-To a solution of 23 g. (0.089 mole) of optically active benzyl-a-d tosylate in 1 1. of dry ethanol was added 250 ml. of distilled water. The solution was maintained at 25' for 4 hours (about 7 half-lives). The solution was neutralized with sodium hydroxide and distilled t o half of its original volume. The residue was diluted with water and the resulting mixture was extracted with ether. Distillation of the washed and dried ether extract left a residue which was heated on a steam-bath for 7 hours with 22.5 g. of recrystallized phthalic anhydride, 30 ml. of dry pyridine and 25 nil. of dry benzene. The mixture was poured into aqueous sodium carbonate and extracted with ether. Distillation of the washed and dried ether extract gave 2.5 ml. of benzyl-aid ~ i: 0.005 , ethyl ether, b. 81-82' (23 mm.), a Z 60.168 a Z 6 5 4 6 1 0.204 =k 0.009' ( I 2). The infrared spectrum was identical with that of benzyl-a-d ethyl ether prepared by other methods. This product was treated with lithium aluminum hydride; the recovered ether had a Z 7 D 0.130 i. 0.003' ( I 1.5). Since this product contained a small amount of alcohol, it was treated with pyridine and phthalic aiihydride as described above; the recovered product had a% 0.086 f 0.004', 0127j461 0.095 z!c 0.010" ( I I), XZ6"D 1.4891. The aqueous carbonate solution was acidified to pH 2 with hydrochloric acid. The crystalline benzyl-a-d hydrogen phthalate which formed on standing was filtered and recrystallized t6 constant rotation from benzene giving product having [ ( Y ] * ~ D-0.209 =k o.oOgo, [a]295m-0.275 i 0.008" ( c 16.4, acetone). Benzyl-a-d hydrogen phthalate prepared directly from the alcohol used t o prepare the tosylate was recrystallized from benzene to constant rotation and had [ a ]2 8 ~ 0.219 f 0.005", CY]^^^^^^ 0.271 f 0.006' (c 19.8, acetone). BERKELEY,CALIF.
