Sept. 20, 1963
COMMUNICATIONS TO THE EDITOR
preparation and gave a sharp, single Pauly-positive spot on paper chromatography (Rf1*0.4,R f l 9 0.5) and a sharp, single Pauly-positive spot on high voltage paper electrophoresis. CombinationQO of the synthetic material obtained by column chromatography with natural B-chainZ1 generated insulin activity in a yield of 0.5-1.2% (corrected for water content). This compares favorably with the activity obtained4,j.'upon recombination of natural A- and B-chains. Insulin activity was determined by the mouse-diaphragm methodzzand by immunological assays. In the latter case the insulin activity was neutralized by anti-ox-insulin serum.23 Our studies toward the synthesis of the B-chain will be reported in a later communication. ( I S ) T h e R f refers t o an ascending chromatography in t h e system (see ref 6) ?-butanol&acetic acid-8 21 urea, 12 5 :0.9: 11.5. (19) T h e R f refers t o a descending chromatography in t h e system (see ref 6) 2-butanol-acetic arid-8 M , urea, 12 5 : 1 : 11.5. ( 2 0 ) \Ye wish t o express our gratitude t o D r . G. H . Dixon a n d Dr. S. Wilson of t h e Department of Biochemistry, a n d Connaught Medical Research Laboratories of t h e University of Toronto, C a n a d a , for carrying out t h e combination experiments of t h e synthetic A-chain with t h e natural Bchain and the biological assays. (21) S a t u r a l B ~ c h a i nfrom ox insulin was used in t h e combination experiments. (22) A . C . Wardlaw and P J. Moloney, Can. J . Biochem. Physiol , 39, 695 (1961). ( 2 3 ) P. J 3Ioloney and M Coval, Biochem. J . , 69, 179 (1955). (24) This work was supported by a Research Career Development Award (G?.I-K3-15151) from t h e Public Health Service and a grant (A-3067) from t h e National Institute of Arthritis and Metabolic Diseases, Public Health Service, for which we wish to express our appreciation. (25) T h e authors wish t o express their appreciation t o Mrs. Jemele Hudson for t h e enzymatic analyses and amino acid analyses and Miss Joanne Janos for technical assistance.
H
Sir: Vinyl cations are reputed to be of relatively high energy as judged in part by the well known unreactivity of vinyl halides toward alcoholic silver nitrate. We wish to report that addition of trifluoroacetic acid to alkynes occurs almost as rapidly (approximately 0.2 as fast) as the previously studied comparable reaction of alkene^.^,^ Vinylic trifluoroacetates are formed which may be regarded as arising from intermediate substituted vinyl cations, as illustrated for the reaction of 1-h e ~ y n e . ~ (1) This research was supported by a grant (790 A) from t h e Petroleum Research F u n d of t h e American Chemical Society. ( 2 ) ( a ) J . Hine, "Physical Organic Chemistry." McGraw-Hill Book Co., Inc., S e w Y o r k , N . Y , 19,56,p. 148. Resonance stabilization of t h e vinyl halides presumably also contributes t o t h e lack of reactivity of these compounds. ( b ) R . L . Shriner, R . C . Fuson, and D. Y . Curtin, "The Systematic Identification of Organic Compounds," 4th E d . , John Wiley and Sons, S e w Y o r k , N Y., I Y J O , p. 141. (c) We have been unable to locate a reference t o a definitive study of t h e reactivity of vinyl halides toward alcoholic silver nitrate. We suspect t h a t t h e widespread familiarity of chemists with t h e s t a t e m e n t in ref. 2b t h a t "vinyl halides. , are u n r e a c t i v e . , ." accounts for the "well known' aspect of t h e reaction. (3) ( a ) P E . Peterson and G Allen, J . Org. Ckem., '27, 1505 (1962); ( b ) P . E. Peterson and G Allen, ibid , 2 7 , 2290 (1962). ( 4 ) T h e hydration of alkynes t o ketones in t h e presence of strong acids has long been known, b u t either concentrated sulfuric acid o r high temperatures have been employed. Cf R . E . Schaad a n d V . K. Ipatieff, J . A m . Chem. S a c , 68, 178 (1940). Addition of hydrogen bromide t o alkynes has been studied: 3 f . S Kharasch, J. G. hIch-ab, a n d & CI..M c N a h , ibid., 67, 21(i:I (1935). ( 5 ) W e employ simple carbonium ion mechanisms in this communication in t h e absence of more detailed information regarding t h e n a t u r e of t h e intermediates or transition s t a t e s involved. From t h e observed Markovnikov
OzCCFi
\
+
H-CEZC-C~H~
/
If vinyl cations are, in fact, intermediates several interesting questions arise. Will the cationic carbon atoms exhibit sp or spz hybridization? Can the ready formation of these presumed energetic ions be accounted for by the high energy of the alkyne starting materials relative to the transition stage for reaction, as might be inferred from the large heats of hydrogenation of alkynes (to alkenes) relative to that of alkenes?6 Will unusual reaction products, possibly characteristic of hot carbonium ions, be formed? Some initial observations concerning reaction products are illustrated by the following equations.
-
c CF3C02H
____t
3-hexyne, 0.1 M
OzCCFs 3-hexen-3-yl trifluoroacetate cis and trans (987, yield by g.c.)
w
=.
hexaethylbenzene ( 2 7 , yield by g.c.)
+
24% hexaethylbenzene dimers trifluoroacetate
4-
3-hexen-3-yl 3-hexyne, 1.4 iW
C'
BIOCHEMISTRY DEPARTMENT PANAYOTIS G . KATSOYANSIS24,26 USIVERSITYOF PITTSBURGH A N D R E W TOMETSKO SCHOOL OF MEDICINE KOUHEIFUKUDA 5-chloro-1-pentyne PITTSBURGH, PEXNSYLVANIA RECEIVEDL ~ U G U S T12, 1963
Possible Vinyl Cation Intermediates, a 1,CChlorine Shift, and a Trimerization in the Reaction of Trifluoroacetic Acid with Alkynes'
2865
'1
L
507, yield, isolated as the hydrolysis product, 4-chloro 4-penten-1-01
The formation of hexaethylbenzene is of interest because products of this type have previously been found most commonly in reactions catalyzed by metallic species and possibly involving cyclobutadiene complexes as intermediates in some instances Although acid-catalyzed trimerizations of alkynes are not completely unknown,* the ready formation of hexaethylbenzene in our reaction takes on added interest when some of the possibilities for classical and/or nonclassical resonance in the presumed intermediate dimeric ion are considered.
R
R
R
R
/
R
R
The reaction of 5-chloro-1-pentyne probably proceeds via the intermediate cyclic ion shown, which, interestorientation a n d from preliminary studies of t h e effect of inductive suhstituents, however, t h e reaction of alkynes is similar t o t h a t ot alkenes in re. gard t o t h e positive character oi t h e transition state. (6) J. B. C o n n , G. B. Kistiakowski, a n d E. A S m i t h , J . A m . Chem. SOL, 61, 1868 (1939). (7) ( a ) Cf.J . C . Sauer a n d T . L. Cairns, ibid.,79, 2650 (19.57); (b) C. McKinley, I n d . Eng. C h e n . . 4 4 $ 995 (1952). (8) See Almedigen, Zh. Russ. F i s . K k i m . Obscheslsa, 13, 392 (1881); Chem. Zenlr., l a , 629 (1881); cf. Beilstein's "Handbuch der Organischen Chemie," 4 t h E d . , Vol. 1, p. 249, for a report of t h e sulfuric acid-catalyzed trimerization of 2-butyne t o hexamethylhenzene.
2866
COMMUNICATIONS TO THE EDITOR
Vol. 85
ingly, opens by attack a t the primary carbon (to the extent of a t least 85% as determined by gas chromatography). I n contrast, addition of trifluoroacetic acid to 5-chloro-1-pentene (which probably also reacts via a cyclic ion, as shown later)g gives exclusively (>95%) the product arising from reaction of trifluoroacetic acid a t the secondary carbon, suggesting car-
c1
\
/
C1
I
CI
bonium ion character in the transition stage for product formation. An analogous interpretation of the product determining step in the reaction of 5-chloro-1-pentyne can be adopted provided the incipient primary carbonium ion formed by ring opening of the cyclic intermediate is more stable than the zlinyl cation which would be formed by the other mode of ring opening. l o
IZI P Xl m b e h a ~ i o r . ~Efforts to explain these steric effects in terms of configuration and conformation are in progress. ( 9 ) T h e alkene formation possibly is d u e t o desulfurization o f an interSee D Denney and hl Bosmediate episul6de by attack of a nucleophile kin, J . A m . Chem. Soc., 82, 4736 (1960).
INSTITUTEOF CHEMICAL BIOLOGY G. E. MCCASLAND UNIVERSITY OF SANFRANCISCO STANLEY FURUTA SASFRANCISCO 17, CALIFORNIA ARTHURFURST RECEIVEDJLTLY 23, 1963 PAULE. PETERSON JAMESE. DUDDEY
(9) P. E. Peterson a n d G. Allen, J . A m . C h e m . Soc., in press. (10) Alternatively the ring opening reaction may possess S Ncharacter ~ in this case.
DEPARTMENT O F CHEMISTRY SAINTLOUISUSIVERSITY SAINTLOUIS,MISSOURI RECEIVED J U N E17, 1963
Anomalous Reduction of a n Epoxycyclohexanetetrol to a Cyclohexenetetrol by Potassium Methyl Xanthate'
Sir: The normal product from reaction of an epoxide with potassium methyl xanthate is a trithiocarbonate.2 For example, the anhydroinositol diketa13I gives a mixture of the trithiocarbonate diketals IV and V.4a The diastereomer I1 similarly gives the trithiocarbonate diketal VI.lb I t was expected t h a t the product from similar treatments of diastereomer IIIeb would also be VI. The actual product, surprisingly, was a colorless (not yellow) crystalline compound, containing no sulfur, with microanalysis corresponding to CI2Hl604. A permanganate test for unsaturation was positive. The product, m.p. 67-68', was finally shown to be the cis-cyclohexenetetrol diketal VI1 of the same reportedfia melting point. I t s identity was established by hydrolysis and acetylation to give the enetetrol tetraacetate, m.p. 102-103' 103' or 104'). The infrared spectrum was identical with t h a t of an authentic sample,' and a mixture melting point was not depressed. The quantity of pure VI1 actually isolated was 31yoof theoretical. Since few methods for regenerating an alkene from its epoxide are a ~ a i l a b l e extension ,~ of this reaction should be useful. However, the most interesting feature at present is the striking stereospecificity which causes diastereomers I and I1 to form trithiocarbonates and little or no alkene, while I11 shows the opposite ( 1 ) Aided by a grant (G-13893-R) lrom the I\-ational Science Foundation. (21 I. Owen. p i o i , J C h r m Soc , 1024 (1860). 1030 (1960)
( 3 ) T h e trtrol formulas I-VI1 should be understood t o represent the corresponding diacetiine ketal?. ( 4 ) f a 1 G E hlcCasland, S F u r u t a , A. Furst. I,. F. Johnson, and J . N. S h o < , l ? r y .J Orf ChPm , 28, 456 ( 1 9 6 3 ) ; ( b ) S F u r u t a , unpublished work. (.5J A mixture nf epoxide diketal. carbon disulfide, potassium hydroxide. and methanol was boiled under reflux for .5 hr or longer B ) ' a i S J .4nyyal, e l n i , J Chem Soc , 37.5 (19.58); ( b ) ibid.. 3691 (1957). 7 ) R Criegee and P Becher, C h e w Bm.. 90, 2518 (18.571 We wish t o thank Prcrfessor Criegee (Dusseldorl) for a sample of his conduritol-D carbonate diacetate This sample was hydr(ilyzed by us with aqueous ethanlic~ r i d i u mhydroxide, and then acetylated. t o provide our authentic cample (81 See S. Winstein and R . Henderson in "Heterocyclic Compounds," V o l I . R Elderfield E d , John Wiley and Sons, Inc , N e w York, N. Y , 1950, p 44
Resolution of a Triarylcarbinol and Stereospecific Substitution Reactions Sir : Satisfactory methods of resolution have been reported for all types of alkyl and arylalkyl secondary'.? and t e r t i a r ~ carbinols ~,~ except for the triarylcarbinols.5,e LVallis6 obtained d-phenylbiphenyl-a-naphthylcarbinol (d-ROH) by treating I-phenylbiphenyl-cu-naphthylmethylthioglycolic acid (l-RSCH2C02H) with silver nitrate in aqueous acetone, b u t this method was termed unsatisfactory. The optically active trityl system appeared to us most attractive for studies of the stereochemistry of substitution processes involving ion pairs because the system appears to be free of complicating side reactions, e . g . , 5 ~ type 2 processes' and elimination reactions. Kinetic and stereochemical studies of optically active trityl derivatives should provide helpful information concerning the mechanism of substitution of trityl compo~nds.~ \Tallis recognized the value of such studies, and interest in stereochemical studies of trityl compounds is heightened by recent development^.^^^ This note presents: (1) evidence that the method of L'allis has an optical yield of GOTo and that by an extension of the method one can obtain optically pure alcohol; (2) a new method of resolution of triarylcarbinols with high optical yield; (3) proof t h a t both of Wallis' stereospecific substitution reactions take the same stereochemical course; and (4) preliminary evidence t h a t Wallis' reactions proceed with retmtion of configuration. Alcohol (d-ROH) prepared by Wallis' method had (C 1.ojO),l0 [ a I z 4 D = +4.4' ( C 0.8 in [ a ] ' * D = +10' (1) A W . Ingersall, "Organic Reactions," Vol. 11, John Wiley and Sons, Inc., New York, N . Y , 1944, p 370. (2) G . H. Green and J. Kenyon. J . Chem SOL.,761 (1950) (3) 'AT. von E. Doering a n d H. H . Zeiss, J . A m Chem Soc., 72, 147 ( I O J O ) (4) H. H . Zeiss,ib$d.,73,2391 (1951). ( 5 ) C . I,. Arcus, J . Kenyon, a n d S J-evin, J . Chem S o r . , 407 (1931). A ( 6 ) E. S. Wallis and F. H . Adams, J . A m Chem SOL.,66, 3838 (1933) second stereospecific reaction w a s the conversion of I-RSCHICOIH t o 1ROEt. (7) E . D . Hughes, C. K . Ingold, S. F. hfok, S. P a t a i , and Y . Packer. J . Chem. Soc., 1220 (1957); S. Winstein a n d G C. Robinson, J . A m . rhein' Soc., 80, 169 (1958). and later papers in this series; C G Swain and E E . Pegues, tbid..8 0 , 812 (19%). (8) C G. Swain and G Tsuchihashi. ibid., 84, 2021 (19612). and reference3 quoted therein. (Q) S . G Smith. T e l v a h e d r o n L e t l e v s , No. 21; 979 (1962), A . Streitwieser, J r . , a n d T . D. Walsh. ibid ,No.1, 27 (1903).
