March 20, 1962
COMMUNICATIONS TO THE EDITOR
major reaction products from dimethylformamide and (H30)2B10H10 are BloH90CHO' and BloHgNThe latter is isolated from aqueous (CH&H-. solution as an acid salt because of its exceedingly weak acidity. B ~ O H ~ N ( C H ~is)such ~ H -a weak acid that OH- does not remove the proton from the quaternary nitrogen. This proton, however, undergoes exchange with deuterium in deuterium oxide, thus demonstrating its lability. Anal. Calcd. for (CH3)3SB10H9N(CH3)2H:C, 25.1; H, 10.5; B, 45.2; N, 5.8; S, 13.4. Found: C,25.3; H, 10.3; B,45.1; K , 5 . 6 ; S,13.3. Calcd. for Cs2BloH90CHO:C, 2.8; H , 2.3; B, 25.0; Cs, 62.1. Found: C, 2.7; H , 2.6; B, 25.3; Cs, 62.0. ( H ~ O ) ~ B ~and O H (H30)2B12H12 ~O react with donor oxygen and sulfur functions in organic compounds to give a variety of derivatives, e.g.
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agreement with this, boron resonance studies show that BloHe[S(CH3)2]2is apically substituted. CONTRIBUTION NO 733 FROM THE U'. H. KNOTH CENTR.4L RESEARCH DEPARTMEFT H . C. MILLER EXPERIMENTAL STATIOX D. C. ENGLAND AFD Co. G. W. PARSHALL E. I DU POSTDE SEMOURS ~YILMINGTOS98, DELAWARE E. L. MCETTERTIES RECEIVED DECEMBER 11, 1961 OBSERVATIONS ON THE MECHANISM OF BloHto-' FORMATION
Sty: The recent preparation' and the proposal of the probable structure2 of the BloHlo-2 ion has led to a study of the mechanism of BloHlo-2 ion formation. As previously described,l the BloHlo-2 ion is formed when members of the B10H12X~ (X = ligand) series are treated with base. An example of this interconversion is shown in (1). The BIOHI~(CH~C 4S 2Et2S )~ + 2Et3NH' 4- BlaHlo-*
+ BCHiCN
(1)
proposed structure of the BloHlo-? ion2 requires a subtle rearrangement of the boron atom configuration present in BIOH1?X2compound^.^ I t was observed4 that the attachment of a S(7)-boron atom to the 9-boron atom of decaborane and then a similar attachment of the 8(10)-boron atom to the 6-position results in the unique formation of Disulfides give thioether derivatives, e.g., BloHs- the proposed BlcHlo-' configuration. The two (SCH&=. Hydrogen halides also react with the ligand molecules and the two bridge hydrogen BIDand B12acids; BI2H8F4-and B1rHl1Cl=have been atoms present in the reactant B10H12X2 molecule obtained in this fashion. Olefins also add readily to are expelled during this reaction. In mechanistic (H30)2B10H10 and (H30)?B1?Hle. Styrene and pro- terms, the bridge hydrogen atoms present in pylene, for example, have given Bl?H,1CH(CH3)- BIOHl2X2may be removed as protons to produce CeHj- and B12H11C3H;=. an intermediate (I) which contains filled ?-center Anal. Calcd. for Cs2B12Brl10H(ex bromination of orbitals between edge neighbors. These two B12H11OH=): Cs, 20.6; B, 10.1; Br, 68.0. Found: filled %center orbitals may then serve as novel Cs, 20.3; B, 9.8; Br, 68.4. Calcd. for Cs2B12HsF4: intramolecular nucleophiles for the displacemeiit B,27.0; F, 15.7. Found: B,27.0; F, 15.7. Calcd. of the ligands, X, from the G and 9 positions. for Cs2Bl2HllCH(CH3)C6H6:C, 31.3; H , 4.6; B, 21.1. Found: C,32.5; H,5.1; B,21.1. I t is also possible to attach dimethyl sulfide to these boron cages, the charge on the resulting species being dependent on the number of such ligands attached. An example is B1OHa [S(CH3)2I2, which can be prepared by the reaction of BloHlo" with dimethyl sulfoxide under acidic conditions. This reaction also gives Bl,H&3(CH&-. dnal. Calcd. for BloHs[S(CH3)2]2:C, 20.0; H, I B,oH:oZ S.4; B, 45.0; S,26.6; mol. wt., 240. Found: C, 20.1; H , S.3; B, 44.4; S, 26.7; mol. wt., 230. The over-all trailsformation of B I O H ~ ~ ( C H ~ C N ) ~ -4s would be expected, the order of reactivity tu- to BloHlo-2 outlined above requires that the two ward electrophilic reagents is BloHlo' > BIOHgS- apices of the proposed D4d polyhedron' be derived (CH312- > BioHs[S(CH3)2]2. from the 3 and 8 or the 7 and 10 boron atoms of The mechanisms of some of these reactions are the decaborane molecule. .I sample of tetraobscure but most of them seem to be electrophilic. deuteriodecaborane, deuterated a t the 2,4 and 1, Stereochemical and mechanism studies have been 3 boron positions was available from another initiated to learn more of this aspect. In prelimi(1) hl. F. Hawthorne and A. R. Pitochelli, J . Ani. Chem. Soc., 81, nary work it has been shown that deuteration of 5519 (1959). BloHlo' under acid conditions occurs most rapidly (2) W. N. Lipscomb, Anthony R. Pitochelli and 11. F. Hawthorne, ibid., 81, 5835 (1959). a t the two apical boron5 atoms and presumably they (3) J. Reddy and W. N. Lipscomb, J . Chenz. P h y s . . 31, 610 (1959), would be the initial site of electrophilic attack. In report the boron atom configuration of BI~HII(CH&!X)? to be essen( 5 ) T h e term "apical boron" refers t o t h e BIQHIQstructure postulated b y W. S . Lipscomb, A. R. Pitochelli and M. F. Hawthorne, J . A m . C h e m . S O L .8, 1 , 5833 (1959).
tially t h a t present in t h e decaborane-14 molecule. (4) Also proposed b y W. AT. Lipscomb, private communication, September, 1960.
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COMMUNICATIONS TO THE EDITOR
study,6 and was converted with triethylamine’ to the B ~ o H B Dion. ~ - ~ The Bl1 n.m.r. spectrum of the latter was compared with that of BloHlo in acetonitrile 6 (in p.p.m. f 0.5 relative to B(OCH8)a)
(EtsNH)*BloHloaxial (Et&JH)nBl&o equatorial (EtaNH)ZBloHsD, axial (EtaNH)pBloHsD, equatorial
18.8 47.0 19.0 48.1
Vol. 84
The base was previously shown2 to be pentacyclic and to contain an isolated double bond. Five of the oxygens were found to be present as hydroxyl, carbomethoxyl and acetoxyl functions.
J S H (in c./s. 2~ 5)
138 125 143 Broad singlet
No change was apparent in the low field doublet ascribed to apical BH units, while appreciable collapse was observed in the high field doublet attributed to the equatorial belt of eight equivalent BH units. Because of the inherent line widths of Bll resonances, line shapes are only moderately sensitive indices of deuteration. At present, we can conclude that a t least 90% of the apical positions of B ~ O H ~ Dcontained ~-~ BH bonds, whereas random distribution of deuteriums would predict BO’%. Thus, the available data are consistent with the proposed structure2 and the mechanism of ion formation outlined here. I t might further be mentioned that infrared studies show B10H10-2does not undergo deuterium exchange with D2O or (Et3ND)+.
CH3 I11
1
IV, Y = c=o
L’, Y = CH,
Structure I has been found to be consonant with all observed spectral and chemical data for vindoline. The stereochemical implications are quite tentative and rest on evidence which will be presented in the full paper. Examination of the n.ni.r. spectrum’ of vindoline allows the assignment of each proton as shown. The assignments, however, deserve some comment. The unsplit peak of the proton on the carbon bearing the acetoxyl moiety shifts to 4.076 in desacetylvindoline. The protons (5) J. A. Dupont and M . F . Hawthorne, Meeting Abstracts, p. 47-K, of the methylene portion of the C-ethyl group 138th Meeting of the American Chemical Society, New York, New are not equivalent and are found as a 12-band York, September 11-16, 1960. multiplet centered a t 1.356 ( J = 7.5 c.P.s.). The KOHM& HAASCOMPANY ANTHONY R. PITOCHELLImethyl triplet, however, is almost symmetrical REDSTONE ARSENAL RAYMOND ETTINGER RESEARCH DIVISION JOHN A. DUPONT in vindoline, being found a t an exceptionally high HUNTSVILLE, ALABAMA M. FREDERICK HAWTHCRNEfield (0.486, J = 7.5 c.P.s.) for a grouping of this type. This high field appears to be the result of RECEIVED DECEMBER 26, 1961 increased shielding by ring currents from the aromatic ring. The coupling constant of the two cis VINCA ALKALOIDS. X’. vinyl protons is J = 10 c.P.s., and one of these THE STRUCTURE OF VINDOLINE (5.886) is further split by two non-equivalent Sir: adjacent protons (6 = 3.4) with coupling constants Vindoline, 2 p 3 C Z ~ H ~ ~ O N ~niajor , is ~the alkaloid J = 5 and 2 C.P.S. in the leaves of Vinca rosea Linn. It occurs not The position of the aromatic methoxyl is show11 only as the free base which possesses little bio- to be a t either C-15 or C-168 by examination of logical activity, but combined with various indolic the typical 1,2,4 aromatic proton pattern (ortho moieties4 i t is ubiquitous in the dimeric Vinca splitting J = 8 c.P.s., meta splitting J = 2.5 c.P.s.). alkaloids such as vinblastine5 (VLB) and leuro- The final selection of C-16 is based on the comparicristine,‘ which are potent oncolytic agcntsS6 son of the infrared and ultraviolet spectra of vinand doline with 6-methoxy-N-methyldihydr~indole~ 7 D E L T A VALUES I by the isolation of ind-N-methylnorhamine (11); - 3.4 m p . 112-114’, hydrochloride map. 232-23(j0, 5.88 molecular weight (M) 212 (by mass spectrometry), XEtOH 243 (37,500), 303 (15,100),336 (4,300), from a soda lime distillation of vindoline a t 325’. This derivative also indicates the position of the N-CHa as being on the anilino nitrogen.’O A 6.08 3.75 2.68
3.80
I (1) Paper IX, G. H. Svoboda, Lloydia, 24, 173 (1961). (2) M . Gorman, N. Neuss, G. H. Svoboda, A. J. Barnes, Jr., and N . J. Cone, J . A m . Pharm. Assoc., Sci. E d . , 48, 256 (1959). (3) G. H. Svoboda, N . Neuss, and M . Gorman, ibid., 48, 659 (1959). (4) M. Gorrnan, N. Neuss, and G. H. Svoboda, J . A m . Chem. Soc., 81, 4745 (1959). (5) Previously called vincaleukoblastne: N . Neuss, M. Gorman, G. H. Svoboda, G. M . Maciak, and C. T. Beer, ibid.. 81, 4754 (1959).
(6) I. S. Johnson, H F. Wright, and G. H . Svoboda, Abslracl of f h e Proc. A m . Assoc. f o r Cancer Research, Vol. 3, No. 4 (1962) (In press) and references cited therein. (7) Spectra recorded on Varian HR-60 in CDCl: with tetramethylsilane as internal standard Values 6(PPM), TMS = 0. (8) For numbering system see C. Djerassi, et a!., Proc. Null. Acad So. US.,48, 113 (1962). (9) Kindly supplied by Dr. A. Hofmann, Sandoz A. G., Basel, Switzerland. (10) The presence of the dimethylene “tryptophan” bridge is also strongly supported by the isolation of ind-N-methylnorharmine and the finding that tryptophan is an excellent in wiwo precursor for vinduline (private communication, R. McMahon and M. Gorman, Eli LIIIY and Company).
