Jan. 20, 1961
489
COXXUNICATIONS TO THE EDITOR
activity. The peptide migrated a t a rate somewhat slower than histidine in 24 hour Partridge paper chromatograms3 and Stein-Moore analysis14 of an acid hydrolysate gave the following amino acid ratios : ser~.~tyrl.~met~ &iso.~phe~. . ~ g l u ~ ,9arg3.lgly2.0l y ~ ~ . ~ p r o ~ . ~ vThe a l ~ ~ average ,4. recovery of individual amino acids was 95%. This first synthesis of a peptide which possesses essentially the full in vivo ascorbic acid depleting and plasma corticosterone elevating activity of the natural corticotropins opens the way to systematic investigations relating peptide structure to this important physiological activity.
n
Fig. 1.-The ( OC)8Fe(oCOT)Fe(CO)a molecule: bond distances average t o 1.39 A. for the two distances a t the ends of the COT residue, 1.49 A. for the two central bonds, and 1.44 A. for the other fey- C-C bonds, all f0.03 A. Fe. , . C distances are 2.06 A. to the end carbon atoms (bonded BIOCHEMISTRY DEPARTMENT KLAUSH0FMANNlS UNIVERSITY OF PITTSBURGH HARUAKI YAJIMA together) and 2.15 A. t? the central four carbon atoms, to be SCHOOL OF MEDICINE ~ ‘ O B O R U YANAIHARAcompared with 2.05 A . for F e . . .C in ferrocene.lB The PITTSBURGH, PENNSYLVANIA TEH-YUNG LIU average Fe-C and CEO distances are 1.76 A. and 1.15 A., SAUL LANDE respectively, in the Fe-CeO groups. RECEIVED DECEMBER 1, 1960 (14) S. Moore, D. H . Spackman and W. H . Stein, Anal. Chem., S O , 1185 (1958). (15) T h e skillful technical assistance of Mrs. Chizuko Yanaihara and Mr. John L. Humes is gratefully acknowledged.
.
directed toward the corresponding Fe atoms, which are actually closer to the bond centers than to the STRUCTURE OF (OCs)Fe( C8H8)Fe(CO)d C atoms themselves. A comparison of distances in Sir: a butadiene type of is not yet availThe cyclooctatetraene (COT) ring has the tub able, but would be of interest. Little T. . .T interform in COT itself1p2 and in the AgCBHg+ ion.3 action between the two halves of the COT complex Electron transfer to the ring to form4 (COT)- and is probable, because of the 96’ t o 101’ angle be(COT)-2 changes the geometry of the original mole- tween ir orbitals as inferred from the assumption of cule to a new form, suggested4 to be the planar sp2hybrids in planes defined by,C-C-C. Also, the form. The many suggestion^^^^^^^^^^^^^ concerning average C-C distance of 1.49A. joining the two the geometry of the (OC)3Fe(COT)Fe(C0)3mole- nearly planar C4 groups seems reasonable for little cule include the tub and planar forms of the (COT) more than a single bond in view of the immediate ring, with mention6 of a ring of Dd symmetry. The strong-bonding coordination numbers, l 4 , I 6 but we do puckered ring of D4d symmetry, which has similar not eliminate a very small T . . .T interaction between molecular orbital degeneracies to those of the the C4 halves. The distortion of sp2bond angles of planar ring, and less strain, but poorer T-T overlap, C8H8 in this complex occurs almost entirely in the central four C-C-C angles, which average to 130’. has not been included in these discussions. We have completed a determination of the struc- As usual, the most naive way of counting electrons ture of a single crystal of (OC)3Fe(COT)Fe(C0)3, around Fe is unbelievably satisfactory. Each C4 which shows a geometry of the COT residue dif- group can be thought of as donating four electrons ferent from any of the above proposals. The ring to its Fe, which already has eight, and receives six (Fig. 1) is oval, but with little residual bonding more from its three CEO groups. Octahedral coexpected across $he closest “noli-bonded” C. . .C ordination is apparent around the Fe, as the three distance of 2.85 A. The form is approximately an C-C bonds are staggered with respect to the three eight membered “chair” form, neither tub nor CEO groups around each corresponding Fe. Howcrown. Each Fe(C0)3 is associated with four CH ever, a more detailed description of the bonding and groups, with each set of 4C forming a planar or back coordination will be deferred until completion nearly planar group, somewhat suggestive of buta- of our study of the (COT)Fe(C0)3structure, presdiene. Assuming very approximate sp2 hybrids in ently in progress. The equivalence of the H1 nuclear magnetic the various C-C-C planes, the 7. . overlap integral resonances5t6 is suggestive of a dynamical effect, of is 0.25 between C&3, but only 0.11 between CI-CZ or C,-C4. All of these T orbitals are fairly well negligible relative chemical shifts of the C-H groups, or of different geometries in the solid and (1) H . S. Kaufman, H . M a r k and I. Fankuchen, Nature, 161, 165 solution. A study of the n.m.r. spectrum of (OC),(1Y48). Fe(COT)Fe(C0)3as a function of temperature may ( 2 ) J. Bregman, private communication. (3) F. S. M a t h e a s and W. N. Lipscomb, J. P h y r . Chon., 63, 845 (1959); also J. A m . Chzm. Soc., 80,4745 (1958). (4) T. J. K a t z and H . L. Strauss, J. Chem. Phrs.. 3 2 , 1873 (1960). ( 5 ) T . A. Manuel and F. G. A. Stone, Proc. Chcm. Soc., 90 (1959). ( 6 ) T . A. Manuel and F. G. A. Stone, J. A m . Chcm. Soc., 84, 336 (1960). (7) A. Nakamura and N . Hagihara, Bull. Chem. SOC.Jofian, 32, 880 (1959). (8) D. A. Brown, J. Znorg. and Nuclear Chsm., 10, 39 (1959); 10, 49 (1959). (9) F. A. Cotton, J . Chcm. Soc. (London), 400 (1960). (10) P. L. PdUSOn, P70G. Chcln. S O C . (London), 297 (19tiO).
(11) H . Rheilin, A. Gruhl, G. Hessling and 0. Pfrangle, Annalen. 482, 161 (1930). (12) B. F. Hallam and P. L. Pauson, J. Chem. S O L .(London), 6413 (1958). (13) R. B. King, T. A. Manuel and F. G. A. Stone, J. Znorf. and Nucl. Chcm., in press. (14) C. C. Costain and B. P. Stoicheff, J. Chcm. P h y s . , 8 0 , 777 (1959). (15) Values of 1.50 A. (C. A. Coulson, “V. Henri Memorial Lectures,” Desoer, Liege, 1948, p. 2 5 ) a n d 1.48 A. (D.W. J. Cruickshank a n d R . A. Sparks, Proc. Roy. Soc., London, 8 2 6 8 , 270 (1960)) have been suggested for a single bond between t w o spa carbon atoms.
490
COMMUNICATIONS TO THE EDITOR
be useful. If the geometry of the CH framework in this compound is in any way indicative of geometry in the (COT)-' or (COT)+ ions, a dynamical effect producing proton equivalence may also be suggested as a possibility here, as well as a tendency toward the crown form. A study of the electron spin resonance a t various temperatures may be of interest in this system of equilibria among ions. The crystals are monoclinic with four molecules i$ a unit cell of parameters a. = 12.53 b = 13.38 A,, c = 8.69 A., and 6 = 111'. The structure was solved by analysis of the three dimensional Patterson function, and refined by least squares procedures. The present agreement factor R = Z [ F o ][Fc]/Z[F~] is 0.10 for the 978 observed reflections.le We wish to ackn~wledge'~ the courtesy of Dr. T. A. Manuel and Dr. F. G. A. Stone for supplying us with samples, and the Office of Naval Research for support.
a.
VOl. s3
metric and combustion methods with satisfactory agreement. The exchange rate is also first order both in deuteroxide and sulfone. TABLE I KIXETICSTUDIESWITH PHESYL 2-OCTYLSULFOXE Entry
Temp., OC.
kn(rac.1 X 104 M - 1 min.-l
k2(exc.) X l o 4 A - 1 min.-I
x
a 72.0 4.6 190 B" 80.1 7.4 ... C" 96.6 33.0 ... Db 80.1 7.6 ... a These values lead to AH* 20 kcal./mole and A&* -25 e.u. b T h i s rate constant was measured for phenyl 2deuterio-2-octyl sulfone in EtOD-DrO ( 2 :1).
From the absence of a substantial kinetic effect on the racemization rate due to a-deuterium (Table I, B and D) we conclude3 that racemization involves an anionic intermediate rather than a concerted proton exchange with hydroxide ion; further, it seems reasonable that concerted proton removal(16) J. D. Dunitz and L. E. Orgel, Proc. Roy. SOL.London, 23, 954 addition is improbable for the deuterium-hydrogen (1955). exchange reaction, especially since the assistance of (17) We also acknowledge receipt of a very recent private communication from 0. S. Mills and G. Robinson, who have i n press in the the sulfonyl group is not called upon for this pathChem. SOC.Proc , a communication on t h e structure of t h e butadiene way. Since Kexc./'krac. = 41 (Table I, A) it appears complex, CdHsFe(C0)8. that the a-sulfonyl carbanion is optically active and DEPARTMENT OF CHEMISTRY BRIANDICKEXS HARVARD UXIVERSITY WILLIAMli.LIPSCOMB its racemization is much slower than p r ~ t o n a t i o n . ~ Kinetic analysis permits distinction between the CAMBRIDGE 38, MASSACHUSETTS two reasonable anionic pathways for sulfone (SH) RECEIVED DECEMBER 7, 1960 racemization-exchange: Scheme I for a single asymSTEREOCHEMISTRY OF ELECTRON metric anion which can be protonated with either DELOCALIZATION INVOLVING &ORBITALS : retention or inversion, and Scheme I1 involving a-SULFONYL CARBANIONS interconversion between two antipodal asymmetric Sir: The traditional analogy between sulfonyl and anions which are protonated stereospecifically. carbonyl functions which depends on the common Scheme I : property of facilitating proton transfer from an adjacent carbon atom by anion stabilization, cannot be extended to the manner in which these groups effect electron delocalization in a-carbanions. Nor does the much-studied enolate structure contribute to the understanding of a-sulfonyl carbanions since the latter uniquely involve the 3d-orbitals of sulfur. We present herein a preliminary report of a study aimed at revealing the stereochemical characteristics of this d-orbital interaction which in measure can be explored using the techniques of the classical ketone a enolate researches. The ratio k 2 , ' k Jmust be -80 for both schemes; In Table I appear kinetic data which have been obtained for hydroxide ion catalyzed racemization Iiowev-er, whereas a normal primary isotope effect and deuterium-hydrogen exchange with phenyl 2 - ( k ' ~k a~ t least 3) for racemization of the a-deuoctyl sulfone in ethanol-water ( 2 : 1 vol.). The terated sulfone is predicted for Scheme I, essentially no isotope effect not far from, and probably optically active sulfone, n1.p. 44-45', [ C ~ ] ? ~-18.8& D 0.3' (c, 0.7 to 1.9 in 2 : 1 ethanol-water), (C, 63.98; somewhat less than, unity) is expected for Scheme (3) T h e kinetic effect of isotropic change of medium clearly is small H, 8.61) was prepared from optically active (-)2octanol,2 [ ( r I z 8 ~ -9.4' (neat), via the toluene- compared t o t h a t for isotopic bond-breaking. See: (a) C. G. Swain, J DiRlilo and J. P. Cordner, J. A m . Chem. Soc., 80, 5983 (1958); sulfonate and phenyl thioether by oxidation of the A. (b) I(.Wiberg, Chem. Rev., 55, 713 (1955): (c) 0. Reitz, Z . g h y s i k . latter with potassium permanganate in acetic acid- Chew., 8 1 1 5 , 257 (1936). (4) D. J . Cram, C. C. Kingsbury and B. Rickhorn, J . A m . Chem. water (the racemic sulfone, m.p. 28-29', was obtained by the same route). Raczmization rates, SOC.,81, 5835 (1959), have observed t h a t D-H exchange proceeds more rapidly t h a n racemization with optically active 2-phenylhutane measured polarimetrically a t 5893 A. were found to and methyl a-phenylethyl ether in teut-butyl alcohol-potassium l e Y l be first order in sulfone and in hydroxide ion. butoxide (ratios ca. 9 and 4). This effect, which disappears with Deuterium exchange rates in O-deuterioethanol- dimethyl sulfoxide a s solvent, has been ascribed t o asymmetric of a planar ion. T h e assumption of a n asymmetric environdeuterium oxide (2: 1) were measured by infrared solvation ment for non-asymmetric a-sulfonyl carbanions (suggested to us by intensity analysis (at 1 0 . 8 8 ~and ) by mass spectro- Professor D . J. Cram) is not a tenable explanation of the above results, (1) J. Hine, "Physical Organic Chemistry," McGraw-Hill Book Co.. Inc., h'ew York, N. Y.. 1956, Chapter 10. (3) "Organic Syntheses," John Wiley and Sons, New York, N. Y . , 2nd Edition, 1941, 418.
since i t is intrinsically unlikely for relatively stable anions (OK,for sulfones N 23) and totally unsatisfactory for aqueous media in which changes in t h e shape of the solvation shell t o fit a symmetric ion should be unimpeded structurally and hence exceedingly rapid.
