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COMMUNICATIONS TO THE EDITOR 9
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Our results show that the reaction of oxalyl chloride with 2-B10H9N(CH3)a- proceeds with a high specificity for equatorial substitution. However, this does not necessarily imply a higher ground state electron density a t equatorial than a t apical positions of the substrate. Indeed there is probably no reason to expect a priori that an orientation-electron density correlation6 should be valid in all instances of polyhedral borane substitution, since correlation of orientation in aromatic substitution reactions with ground-state electron densities a t various positions of aromatic rings is not rigorous from the viewpoint of transition-state theory.I3 In particular, the lack of knowledge of mechanistic details in electrophilic substitution reactions on polyhedral boranes makes an understanding of orientation effects in these reactions excecdingly difficult. Acknowledgment.-The author gratefully acknowledges the determination of the ORD curves by Dr. LT. E. Shashoua. (13) See, for example, J. Hine, "Physical Organic Chemistry," McGrawHill Book Co., I n c , New York, h-,Y . , 1956, p. 351, and references cited therein.
CONTRIBUTION KO. 987 CEKTRAL RESEARCH DEPARTMENT EXPERIMENTAL STATION E. I. DU P O K T D E h-EMOURS AND C O M P A N Y WILMINCTOX 98, DELAWARE RECEIVED MAY21, 1964
I
I
I
I
I
I
I
I
250
300
350
400
450
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W . R. HERTLER
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X (mp) Fig. 2.--h, ultraviolet spectrum of 2,7(8)-I in methylene chloride (8320 540); B, ORD curve of (+)2,7- (or 2,8-) I in methylene chloride ( c 0.036); C, ORD curve of (+)2,7- (or 2,8-) I in acetonitrile ( c 2 . 5 ) ; D, O R D curve of ( + ) 2 , 7 - (or 2 , 8 - ) I1 in acetonitrile ( c 2.5).
temperatures were not investigated because slow decomposition was apparent above 200'. (+)2,7- (or 2,s-) I was converted as shown in eq. 1 to (+)2,7(or 2,8-) B:oHs[N(CH3)3]2 with [ a I z 5 D $13' (c 1.9, acetonitrile). Figure 1 indicates the enantiomeric relationship of 2,7- and 2,8-11. The existence of (+)BloHa [N(CH3)3]2 (11) precludes any geometry" other than 2,7(8)- or 2,6(9)- for I1 and hence for I. 2,6(9)geometry appears unreasonable on both steric and electronic grounds. The optical data confirm the Bl1 n.m.r. assignment for 2,7(8)-II.a 2,7(S)-II undergoes polyhedral isomerization12 a t temperatures in the vicinity of 300°, and details of this isomerization will be reported subsequently. The optical rotatory dispersion (ORD) curves of ( + ) 2 , 7 - (or 2,s-) I and (+)2,7- (or 2,s-)I1 (Fig. 2) confirm the configurational relationship of the two compounds. The positive Cotton effect superimposed on the plain ORD curve of (+)2,7- (or 2,s-)I corresponds to a shoulder in the ultraviolet spectrum of I a t -320 mp (e 540) which may arise from an n -.t r* transition. (11) Of t h e nine possible isomers of I. three are d l - pairs, ~ i e . the , 2,3(5)-, 2,6(9)-, and 2,7(8)- isomers. Two of the seven possible isomers of 11 are di- pairs, uiz.,the 2,6(9)- and 2,7(8)-isomers. (12) For discussions of polyhedral isomerization processes see K . Hoffmann and TI; N. Lipscomb, I n o r p . Chem.. 2. 231 (1963), and A. Kaczmarczyk. R . 11. Dobrott, and W. N . Lipscomb, Pvnc. N a i l . A c a d . Sci. C . S.,48, 729 (1962). See also M . F. Hawthorne, R . L. Pilling. P. F. Stokely, and P. M . Garrett, J . A m . Chem. Soc., 86, 3704 (1963).
Isoracemization of Trialkylammonium Carbanide Ion Pairs'
Sir: Previous publications have reported results of investigations of the base-catalyzed isotopic exchange reaction of carbon with oxygen acids. The stereochemistry of the reaction was derived from the relative exchange (rate constant k,) and racemization (rate constant k,) rates. Values of the ratio kel'k, have been obtained which indicate that electrophilic substitution can occur with retention (k,;'k, >>1), complete racemization (ke/k, = I), or inversion (ke,!k, = 0.5 to l ) . ? We now report k,!k, values which are less than 0.5, and evidence for occurrence of a base-catalyzed intramolecular racemization reaction is presented. Compounds I and I1 were prepared by conventional reactions in optically active form with and without deuterium in the indicated position^.^ Table I records the results of the exchange-racemization experiments, as well as the reaction conditions and physical properties of the two substrates.
. .
Id
IId, X = NOz IIId, X = H
(1) This work was supported by a grant from the Petroleum Research Fund administered by the American Chemical Society. Grateful acknowledgment is hereby made to donors of this fund. ( 2 ) D. J. Cram and I,, Gosser, J . A m Chem. Soc., 86, 3890 (1963). and earlier papers. (3) Elemental analysis of all new compounds gave values within 0.3% of theory, whereas the physical properties of known compounds correspond t o literature values.
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295 1
TABLEI
RATIOSOF X’ALUES
RATE CONSTANTSO FOR BASE-CATALYZED DEUTERIUM-HYDROGEX EXCHANGE ( k , ) A N D RACEMIZATION ( k , ) of 2-PHENYLBCTYRONTRILE( I ) A N D 2-h‘,N-DIMETHYLAMIDO-9-METHYL-7-NITROFLUORENE (11)
OF
--Substrate-Run no.
,------
Concn., Nature
.M
Base---Concn.,
Nature
M
Solvent
T , OC
Time, hr.
%
% rat.'
k,/ka
72 57 1 5 0 . 5 0 (CH3)aCOH 145 14 XH3 0 10 1.0 41 42 50 3 0 07 SH3 0 . 3 0 CH30H 1. 0 25 3 44 43 SH3 0 . 2 0 ( CHB)*SO 0.06 50 4.5 32 37 0.84 4 0.40 (n-C3H7)3S 0 . 3 0 CH30H 20 70 0.19 145 14 (n-C3H7)3X 0 50 (CH3)sCOH 5 0 20 6 (-)-Ih‘ 0 30 (n-C3H3)3S 0 50 (CH3)3COD’ 145 7 12 48 0.20 7 ( +)-Idd 0.07 (n-C3H7)3S 0 . 6 0 (CH2)40-(CH3)aCOH’ 160 28 6 74 0.05 11 74 0.09 23 160 0 . 6 0 (CH2)40-(CH3)3COH’.h (n-CaHi)aS 8 ( +)-Idd 0 07 0.19 23 25 79 160 9 ( +)-Idd (x-C3Hi)3S 0 . 6 0 (CH2)40-(CH3)3COH8“ 0.07 50 10 6 131 1 10 ( +)-IId’ 0.05 P-CHaCeH4XH2 0 . 5 0 (CH2)aO 0.5 10 11 1 -22 11 (+)-IId’ 0.01 n-CaH,NHz 0 . 1 0 (CH2)aO 2 48 99 0.1 12 (+)-IIhb 0 07 (n-C3H7)3S 0 . 6 0 ( C H ~ ) ~ O - ( C H B ) ~ C O D ” ’ 75 35 100 k3. Two more specific mechanisms can be envisioned for the racemization of the ion pair (step governed by ks). In the first, the carbanion simply rotates 180’ (with respect to the tripropylammonium ion) around any axis which passes through the plane of the carbanion, and does this repeatedly. In the second, which might be called a “conducted tour ( 4 ) T h e authors thank Prof. P. D. Bartlett for suggesting this term.
optically active or racemic
optically active
racemic
optically active or racemic
racemic
mechanism,” the deuterium attached to carbon becomes hydrogen bonded or even covalently bound to the nitrogen of nitrile I or the oxygen of the nitro group of 11. In further stages, the deuterium could be moved by the amine catalyst from the hetero atom back to carbon on the side remote from its original residence. Base-catalyzed intramolecular rearrangements have been ~ b s e r v e d . ~ In runs 1-4, nitrile Id exhibits behavior qualitatively similar to that of amide IIId.2 Although exchange occurred with net retention in t-butyl alcohol-ammonia in both systems, I d gave kJk, = 1.5, whereas IIId gave >50. Probably isoracemization competes with retention more effectively in nitrile Id than in amide IIId. Both systems underwent exchange with racemization in methanol-ammonia and dimethyl sulfoxideammonia (ke:’k, = l ) , and both systems gave net inversion in methanol-tripropylamine (kel k, = 0.840.69). Nitroamide IId in tetrahydrofuran-n-propylamine gave ke/k, = 1 (run l l ) , whereas amide IIId with the same solvent-base gave k e ’ k , = > 5 6 . 2 When p toluidine was substituted for n-propylamine in run 10, (5) (a) D.J. Cram and R . T. Uyeda, J . A m Chem. Soc., 8 4 , 4358 (1962), ( b ) S. Bank, C. A. Rowe, J r . , and A. Schriesheim, ibtd., 86, 2115 (1963); (c) W. yon’ E . Doering and P. P. Gaspar, ibid., 86, 3043 (1963)’ (d) G Bergson and A. M. Weidler, Acto Chem. Scond., 17, 862 (1963).
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nitroamide IId gave k , / k , = 6. These data highlight the dependence of the stereochemistry of the reaction on the acid-base strength relationships, which relate to the rate of the proton capture by the carbanion. CONTRIBUTION No. 1698 DONALD J. CRAM OF CHEMISTRY LAWRENCE GOSSER DEPARTMENT THEUNIVERSITY OF CALIFORNIA AT Los ANCELES Los AXCELES24, CAL~FORNIA RECEIVED J U N E4, 1964
3 '-Deoxynucleosides. I. A Synthesis of 3'-Deoxyadenosine
Sir : The identity of cordycepin with 3/-deoxyadenosine (I) has recently been reported. 3'-Deoxyadenosine has been shown to inhibit the growth of KB cell cul-
OH I
tures,2 B . ~ u b t i l i s ,an ~ avian tubercle b a ~ i l l u s ,and ~ Ehrlich ascites carcinoma4 in mice, but its effects on other animal tumor systems have not yet been reported. In contrast to the large amount of work, both chemical and biological, carried out on 2'-deoxynucleosides, of the 3'-deoxynucleosides only 3'-deox yadenosine5S6and 3'-deoxyuridine' appear t o have been reported. Consequently, even though 3'-deoxyadenosine has been synthesized5j6 previously, we are now reporting its synthesis by a route providing a 3-deoxyribose derivative useful for synthesis of large amounts of 3'-deoxyadenosine, as well as being amenable to synthesis of 3'-deoxyadenosine-8-C14and other 3'-deoxynucleosides. For synthesis of 3'-deoxynucleosides, 2,5-di-O-benzoy~-3-deoxy-~-ribofuranosy~ bromide (11) was chosen as a generally useful intermediate. Preparation of
Vol. 86
this new 3-deoxyribose derivative utilized methyl 2,3anhydro-p-D-ribofuranoside ( I I I ) Bas the starting material. Stereospecific reduction of the epoxide function in I11 by hydrogenation in ethanol over a Raney nickel catalyst a t 80' and 40 p.s.i.g. gave almost exclusively the 3-deoxyribose derivative, methyl 3-deoxy-@-u-ribofuranoside (IV) , characterized by its infrared spectrum [2.92 (OH), 3.52 (OCHs), ,no band a t 11.6 p (epoxide)] and n.m.r. spectrum [GO Mc., in CDCl,, using a Varian Associates Model 4300B spectrometer : 0-methyl protons, T 6.16; C-1 proton, T 5 2 2 (singlet)]. Benzoylation of IV with benzoyl chloride and pyridine gave methyl 2,5-di-O-benzoyl-3-deoxy-~-~-ribofuranoside (V), m.p. 80-81'. characterized by infrared and n.m.r. spectra and elemental analysis. Direct conversion of this methyl glycoside (V) to 2,5-di-O-benzoyl-3-deoxyD-ribofuranosyl bromide (I I ) was accomplished by reaction with ten parts of a 16% solution of hydrogen bromide in acetic acid a t 25' for 20 min. After removal of the solvents, I1 was obtained as an oil. Its n.m.r. spectrum no longer showed a band characteristic of the methoxyl function and the C-1 proton band was shifted downfield to T 3.43. The bromo sugar I1 was coupled with chloromercuri6-benzamidop~rine~ in refluxing xylene (15 min.) to give 6-benzamido-9-(2,~-di-O-benzoyl-3-deoxy-~-~-ribofuranosyl)purine, which on treatment with sodium methoxide in methanol gave 3'-deoxyadenosine (I), m.p. 224-225'; its infrared spectrum in Nujol was identical with that of an authentic sample. Acknowledgment.-We are indebted to Dr. Nelson R. Trenner and h4r. Byron Arison for the n.m.r. spectra and their interpretation. (8) C . D . Anderson, L Goodman, a n d B. R. Baker, J . A m . Chem. SOL., 80, 5247 (1958). (9) C . D . Anderson, L. Goodman, a n d B. R . Baker, i b i d . , 81, 3967 (1959).
MERCKSHARP& DOHMERESEARCH LABORATORIES DIVISIONOF MERCK& Co., INC. RAHWAY, NEW JERSEY
RECEIVED JUNE
EDWARD WALTOX RUTHF. NUTT SUSAN R . JEXKIKS FREDERICK W . HOLLY 9, 1964
Specific Reaction Rate of the Second-Order Formation of Arz+
Sir : 0 111 111
OR' 0
(1) E . A . Kaczka, N. R. Trenner, B. Arison, R. W. Walker, and K . Folkers, Biochem Biophrs. Res. Commun., 14, 456 (1964). ( 2 ) E. A. Kaczka, E . L. Dulaney, C . 0 . Gitterman, H . B. Woodruff, and K . Folkers, i b i d . , 14, 452 (1964). (3) K . G Cunningham. S. A . Hutchinson, W. Manson, a n d F. S.Spring, J C h r m . S o c . , 2299 (1951). (4) I) T' Jagger, N M . Kredich, and A J . Guarino, Cancer Res., 21, 216 (1961) ( 5 ) W. W Lee, A . Benitez, C . D. Anderson, L. Goodman, and B. R . Baker, J A m . Chcm. Soc., 83, 1906 (1961). (6) A Todd a n d T L. V Ulbricht, J Chem. Soc., 3275 (1960). ( 7 ) I). h1. Brown. D . B. Parihar, A. R . T o d d , and S . T'aradarajan, i b i d . , 3028 11958).
The formation of AT1+ by a bimolecular reaction involving an excited argon atom was first reported by Hornbeck and Molnar.' More recently, Fuchs and Kau12 and Dahler, Franklin, Munson, and Field3 reported kinetic studies of this second-order reaction. In neither of these latter mass spectrometric s t ~ d i e s * ~ ~ (which employed continuous electron beams and ionrepeller fields) could the specific reaction rate be determined explicitly because the reaction time, T , was not known; the product of specific reaction rate and reaction time, k T , was reported. Combination of k T values with the usual sec. radiative lifetime leads to astonishingly high rate constants. Recently, Kau14 has reported that three excited states of argon, with an (1) J. A. Hornbeck a n d J . P . Molnar. Phys. Rev., 84, 621 (1951). ( 2 ) R . F u c h s a n d W. Kaul, Z . Nalurfovsch., 16, 108 (1960). (3) J . S. Dahler, J. I, Franklin, hl. S. B. Munson, and F . H . Field, J . Chrm. P h y s . , 36,332 (1962). (4) W. Kaul, V I International Conference on Ionization Phenomena in Gases. Paris, 1963, p . 169
