Dec. 20, 1059
COMMCNICATIONS TO THE EDITOR
gives even higher log Q1 values than reported in Table 11. This suggests that this peptide probably shows some increased complex stability arising from electron release by the methyl group, enhanced in this instance by the positive character of the adjacent peptide nitrogen. The small size of the methyl group does not produce any steric interference in the complex formation. A similar electronic effect might be expected with the benzyl group particularly under the influence of the positive peptide nitrogen, but the glycylphenylalanines show about the same stability as glycylglycine. A study of Fisher-Hirschfelder scale models shows that the phenyl ring does not directly interfere with chelation a t the peptide bond, but when chelation occurs, the bulky phenyl ring is forced into close proximity to other atoms in the molecule. Such steric interaction may offset any electronic influence present. The over-all stability constants (log Q1Q2) given in Table I1 and summarized in Fig. 2 show the same general trends revealed by the constants involving the uptake of the first peptide molecule, although the calculated differences are greater. This is to be expected if steric factors are important, for the presence of two phenyl groups in these complex structures should increase the steric interferences compared to structures containing only one ligand molecule. Calculations using pK'2 = 8.16
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for both glycylphenylalanines give stability constants for the D-isomer of 5.30 with cobalt and 8.58 with copper. The diEerences recorded in Table I1 for these peptides thus appear to be the result of reasonable experimental error in the determination of p K l g rather than a real variation in complex stabilities. I t is apparent that variations in stability constants of dipeptide-metal ion complexes can be correlated with peptide structures. The variations can to some extent be ascribed to the electronreleasing or withdrawing character of the group attached to the 0-carbon, but steric interferences may be more significant when large side chains are present, particularly adjacent to the peptide bond. The results show that the largest changes occur when structural changes significantly alter the basic strength of the terminal amino group. Structural changes adjacent to the peptide bond are much less effective in altering complex stability. It has been observed that small differences in the amino dissociation constants employed can lead to relatively large and apparently significant variations in computed stability constants. Direct comparison of stability constants must, therefore, be made with extreme caution and with a knowledge of the correctness of the dissociation constants used in the calculations. SYRACUSE 10, N. Y .
COMMUNICATIONS T O T H E EDITOR
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PHOTOCHEMICAL TRANSFORMATIONS. V. THE REACTION OF 3,5-CHOLESTADlENE',2
Sir: The photochemical sensitivity of homoannular and we now wish to dienes is well report a photochemical induced transformation of a heteroannular diene. The tetracyclic 3,5-cholestadiene, I (C27H44),in ethanol, upon irradiation with a mercury arc yielded 50y0 of an ethyl ether of a pentacyclic O ~ , 104-105", [ c ~ ] ~ ~ D sterol,6 11, ( C ! Z & ~ m.p. 18.3", €200 100, vmax 3030 cm.-l). I1 upon treatment with alumina a t room temperature? lost one mole of ethanol and gave rise to an olefin, 111 (C27H44, m.p. 109.5-110.2", [0]"D f 41", Amax 207 mp ( E 12,000), n.m.r., two vinyl hydrogens) which, in turn, upon reaction with osmium tetroxide yielded
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( I ) For paper I V , see W. G. Dauben, K . Koch and W. E. Thiessen, THISJOURNAL, in press. (2) This work was supported in part by Grant No. A-709(C6)-B-10, U. S. Public Health Service. (3) L. Velluz, G. Amiard and B. Goffinet, Bull. soc. chim. France, 882 (1957); M . P. Rappoldt, J. A. Keverling-Busiman and E. Havinga, Rec. trav. chim., 77, 327 (1958); R. J. DeKoch, Doctoral Dissertation, University of Leiden. (4) D . H. R. Barton and A. S. Kende, J. Chem. SOC.,688 (1958); R. L. Autrey, D. H . R . Barton and W. H. Rausch, Proc. Chem. Soc., 55 (1959). (5) W. G. Dauben and G. J. Fonken, THIS JOURNAL, 81,4060 (1959). ( 6 ) All analyses are in agreement with the theoretical valuer. (7) A. Romeo and R. Villotti, A n n . Chim. (Rome),47, 081 (1967); C. A , , 62, 1194 (1958).
a saturated diol (m.p. 132-134", [ c Y ] ~ ~ D 5 2 " , e200 100). These data establish in I1 a cyclopropylcarbinyl ethyl ether grouping such as is found in a 3,5-cycl0-6-01steroid.
CSH,;
OC2Hj 11
VI
aEL p3 fI
I11
CI-I,OH IT'
VI1
IX
I1 upon reaction with aqueous acid in acetone yielded a p, younsaturated primary alcohol, I V ( m p . 102-103 , [ c r I z 5 ~-45", no reaction with MnOe in acetone), and Oppenauer oxidation of IV gave rise to an oily a$-unsaturated aldehyde (v,,, 2700, 1668, 1630 cm.-'; 2,4-dinitrophenyl-
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CORlMUNICBTIONS T O T H E
Vol. 81
EDITOR
co--0 hydrazone, m.p. 226-229", Xmax 390 mp ( E 20,000)). I I Dihydrogenation of IV yielded a saturated alcohol, v (m.p. 89.6-90.2", [ c u ] " ~ - 3.6"), which was converted into a crystalline tosylate (m.p. 89.090.5", [cuIz5D 3.6'). The tosylate upon reaction with activity 111 alumina yielded olefin VI (m.p. 90.6-91.8", [ C X ] ~ ~ D 88.2") which possessed an exocyclic methylene group (vmax 580 cm. -I). Ozonolysis of VI gave rise to formaldehyde and the known A-norcoprostane-3-one8 (m.p . 75.8-76. 8" , [ c ~ ] * ~ D 126"; semicarbazone, m.p. 265-265"). The tosylate upon reaction with activity I alumina yielded the known olefin, 3-methyl-A3(5)-,4-nor\'I CH2-( Hj cholestene, VIII' (m.p. 63-64", [ c u ] ' j ~ 59.6"; I I1 - 2 IT? ( o*i identical with authentic sample). These data establish the structure of IV and show that no 111 asymmetric centers present in the original diene - I1.0 ~. -_ have been affected in the irradiation reaction. When the structure of IV is coupled with the (OOH " COOH fact that I1 can be transformed to a conjugated '\/ ' O()H ( "I" vq ('OOH cyclopropane-ene possessing two vinyl hydrogens, only the 6-ethoxy-3,5-cyclosteroid structure I1 is ' 4 possible. Since either the 6cu- or 6p-oxy derivatives 01 I1 of 3cu,5cu-cyclocholestaneare known to yield cholesCOOH COOI{ terol under the conditions in which I1 yielded IV,'O C,H, c, H ' c 00 I i , C OOH \ the difference must lie in the stereochemistry of the cyclopropane ring, and I1 must possess the 30,5pc' cyclo structure shown in X. The mechanistic \ I\ implications of the diaxial elimination leading C , 67.18; H, 4 . 7 8 ) . The residue from the inethfrom I1 to IV will be discussed in the completed anolic extract was distilled a t reduced pressure manuscript. gil-ing 4-phenylcyclohept-4-ene- 1,%dicarboxylic 311(8) A. Windaus, Bey., 62, 170 (1919), B B Smith and H. R. h-ace, hydride (111) (40y0yield) as light-yellow oil ( THISJOURNAL, 76, 6119 (1952). 170-1S0" (2 mm.), A,, 240 nip, E S.500, X (9) H. Schmid and K. Kagi, Helu. Chtm. A d a , 33, 1582 (19.50) 5.60p, 5.80p; anal. found for C15H1403: E , T 3 . S ; (10) S Winstein and E. M. Kosower, THIS JOURNAI., 81, 4399 (1959). H, 6.1; mol. wt., 228 (benzene); s a p . equiv., WILLIAMG. DACBES 115). In platinum-catalyzed hydrogenation I11 DEPARTMENT O F CHEMISTRY JAMES A. Ross UNIVERSITY OF CALIFORNIA absorbed one mole of hydrogen, providing an oily BERKELEY 4, CALIFORSIA dihydro derivative having no maximum a t 240 mp. RECEIVEDOCTOBER 22, 1959 Oxidation of 111by means of CrO3-H2S04 provided benzoic acid. Hydrolysis of I11 and chromatogA NOVEL CONJUGATIVE 1,s-ADDITION REACTION raphy over Florisil provided two isomeric diacids: (1) (IV) m.p. 103-105', XEzH 211 mp INVOLVING THE VlNYLCYCLOPROPANE SYSTEM ( E 11800), 243 m p ( E 11400); ; :A : 3 . 8 2 ~(anal. ~ Sir: found for C15H&.H20: C , 64.5; H, 6.2), and (2) Although there is considerable evidence that (V) m.p. 190-192", 233-236 my ( E SOOO), B ~ 5 . 5 2 ~5~ . 8 8 ~(anal. found for C15H1604: C, cyclopropane can enter into conjugation similarly x Xmax to a double-bond,l no evidence exists of a successful 69.29; H, 6.15). Compounds 1lTand V show no cyclic addition reaction involving either a vinyl- bands for C-methyl in the infrared. The distilcyclopropane2or a dicyclopropy13system, analogous lation of I11 was accompanied with white crystals to the Diels-Alder reaction. This communication of a new @-lactone(VI) (9% yield) (m.p. lA1-162", presents evidence that vinylcyclopropane is an XE,t,o," 230 mp ( E 6300), 277 mp ( E 6600),::A: 5.5~; active conjugated system when properly activated, anal. found for CI4Hl0O2:C, S 0 , 2 ; H, 3.1; mol. for example, by a phenyl substituent. wt., 202 (ethylene dibromide)). The thermal oxi-4 mixture of equimolar quantities of cu-cyclo- dative-decarbonylation reaction of I11 and the 242 mb (E 9700) and maleic physical and chemical properties of VI will be dispropylstyrene (I)","A,: anhydride in dry benzene was refluxed for 38 hours. cussed in the full paper. After removal of solvent and starting materials JVe observed that I does not isomerize on being the residue was extracted with methanol leaving heated in benzene for 48 hours with 10ycmole of behind an insoluble white bis-adduct (11) (12% maleic anhydride. The palladium-catalyzed addiyield), m.p. 255-257", showing no bands for tion of one mole of hydrogen to I provided 2phenyl in the infrared (Anal. Found for C19H1006: phenylpent-2-ene (VII) 244 mp, 44 5 ) in quantitative yield. The osmium tetroxide(1) For more fully documented accounts of certain aspects of t h e problem see E. N. Trachtenberg and G. Odian, THISJ O C R N A L , 8 0 , catalyzed periodate oxidation of VI1 afforded 4013 (1958). acetophenone as the only identifiable ketone. (2) R. van Volkenburgh, K. W. Greenlee. J. 11, Derfer and C. E. The data clearly indicate that I adds maleic Boord, ibid.,71, 172, 3505 (1945). anhydride by two different route5 under t h e sainc ( 3 ) I,. 1. Smith and E. R. Ropier, ibid., 73, 3310 ( 1 D ; l ) .
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