July 5, 1956
COXMUNICATIONS TO THE EDITOR
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communication reports an unambiguous synthesis of ring size on the nuclear magnetic resonance of apogossypol hexamethyl ether, identical in all signals. Accordingly, the proton signals from a respects with that obtained from I (natural prod- number of polycyclic compounds have been exuct m.p. 277-278"; synthetic product m p . 277- amined (Table I). The shifts are measured rela279" ; mixed m.p. 277-278' ; infrared spectra in- tive to the main peak due to the rest of the arodistinguishable) ,j which establishes conclusively the matic hydrogens. Usually the distance of the correctness of the original Adams formulation. two peaks from a standard marker (cyclohexane or Compound I1 was synthesized by the oxidative decalin when the latter was used as solvent) were measured. The strong interaction found in benzocoupling of S-isopropyl-G,7-dimethoxy-3-methyl-1naphthol (111) m.p. 129-13O0, found; C, 73.76; phenanthrene is considerably weakened by the H, 7.78)6 with. ferric chloride in dioxane as the change in angle introduced by the 5-membered solvent and subsequent methylation of the resulting ring in dibenzofluorene, and the initially weaker 2,2' - bi - 1 - (5 - isopropyl - 6,7 - dimethoxy - 3- phenanthrene interaction is similarly much remethyl)-naphthol (m.p. 271-275", found: C, duced in fluorene and completely removed in 74.21; H, 7.39). Consideration of models demon- fluoranthene, where the hydrogen atoms are even strates that no coupling in the 4position of I11 farther apart. can occur due to steric hindrance. TABLE I H-H distance A Shift, cycles Compound I11 was prepared in the following manner : formylation of 3-isopropyl- 1,2-dimethoxyben- 3,4Benzophenanthrene 0.53 68 1.71 45 zene7,* gave 2-isopropyl-3,4-dimethoxybenzalde-1,2,5,6-Dibenzanthracene hyde (IV), b.p. 98-102" (0.13 mm.) (2,4-dinitro- 1,2,5,6-Dibenzfluorene 1,73 40 1.76 42 phenylhydrazone, m.p. 190-192', found: C, 55.79; Phenanthrene 2.72 12 uncertain H, 5.58). Oxidation of IV gave 2-isopropyl-3,4- Fluorene 0 uncertain dimethoxybenzoic acid as shown by comparison Fluoranthene 2.95 with an authentic sample.g The Stobbe reaction A fairly simple relation exists between the of IV and diethyl succinate with subsequent ring nuclear magnetic resonance shift and the hydrogenclosure (sodium acetate and acetic anhydride) and saponification in the conventional manner hydrogen distance. However, since the H-H distances are calculated on the basis of a planar molegave l-hydroxy-5-isopropyl-G,7-diniethoxy-3-naphthoic acid (m.p. 226-227", found: C, 66.32; H, cule and the H-H repulsion must distort the mole6.34). Reduction with lithium aluminum hydride cule somewhat out of plane, these values are not the true equilibrium H-H distances. Allowance for gave . 3-hydroxymethyl-5-isopropyl-6,7-dimethoxy1-naphthol (m.p. 207-209", found: C, 69.71; this fact would increase the small H-H distances H, 7.20). Hydrogenolysis with palladium on char- proportionally more than the large ones. X consideration of other molecules with interactcoal in methanol with a trace of hydrochloric acid ing protons shows some interesting effects. Perylgave 111. The interest and encouragement of Professor ene with two sterically interfering pairs each tending to twist the molecule out of plane about the R. B. Turner is gratefully acknowledged. central pair of bonds shows a shift of only 25 cycles, ( 5 ) Perkin-Elmer Model 21 Spectrophotometer, 0.11-mm. cells, solabout half that observed for phenanthrene. The v e n t chloroform, concn. 7Y0 doubled torque has clearly effected an increased (6) All analyses b y Huffman Xicroanalytical Laboratories, Wheatridge, Colorado. twist, so that the protons in each pair are con(7) R Adams, M .H u n t a n d R. C. Morris, THIS J O U R N A L60, , 2972 siderably farther apart than in phenanthrene. (1938). Chrysene also has two interacting pairs, but now ( 8 ) J. D. Edwards, Jr., a n d J. L . Cashaw, J . Ovs. Chem., 20, 817 the torque is across a 3-bond rather than a two(1955). bond system. Correspondingly we find a shift (9) R. Adams a n d B. R. Baker, THISJ O U R N A L , 61, 1138 (1939). intermediate between that of phenanthrene and RESEARCH LABORATORIES J . D. EDWARDS, JR. VETERANS-%DMISISTRATIOX HOSPITAL J. L. CASHAW perylene (35 cycles). A more detailed examination HOCSTOX, TEXAS of this kind of structural effect will be published RECEIVED MAY21, 1956 shortly. One is easily convinced from the molecular models that the 4-5 proton repulsion in phenanNUCLEAR MAGNETIC RESONANCE STERIC SHIFTS threne puts the maximum strain on the C9-Cl0 IN -CH GROUPS bond. The anomalously high "K region" reactivSir : ity which is greater than predicted by molecular Sterically interfering hydrogen atoms in the 4-5 orbital theory based on a planar molecule is no position of phenanthrene and many similar mole- doubt due to this fact. A study of the shifts in cules shows up strongly in high resolution nuclear carcinogenic hydrocarbons is also in progress. magnetic resonance experiments. Since the work It has been pointed out to the author2 that the of Arnold, et uZ.,I on the steric effects of methylene closeness of the proton to two aromatic rings groups in hydrindene and tetralin with a-sub- rather than one may result in the kind of shift obstituents in the aromatic ring shows clearly that served. An investigation of the relative importhe interaction is much greater when both rings tance of the two factors is under way. are six-membered than when one of them is fiveThe work reported here was done using a Varian membered, it is of interest to investigate the effect Associates Model V4300 spectrometer working a t ( I ) R. T. Arnold, V. J. Webers a n d R . M. Dodson. THISJOURNAL, 7 4 , 868 (1952).
(2) W . G. Schneider, H. J. Bernstein a n d J. A. Pople, private communication
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VOl. 7s
COMMUNICATIONS TO THE EDITOR
40 mc. and was made possible by grants from the National Research Council of Canada and the National Cancer Institute of Canada.
way..' Water-soluble products were isolated by continuous ether extraction. Mixtures of solid products (entries 10-13) were analyzed by chromatographic separation. Liquid mixtures (entries DEPARTMENT OF CHEMISTRY UNIVERSITY OF BRITISHCOLUMBIA C. REID 1, 2, 5-9) were analyzed by mass spectrometry; VANCOUVER, CANADA in most cases the analyses were checked by infraRECEIVED MAY1, 1956 red comparison with synthetic mixtures. The reduction mixture for experiments 2 , 6, 7, 9, 11 and ANOMALOUS REDUCTION OF EPOXIDES WITH 13 was obtained by adding standardized ethereal LITHIUM ALUMINUM HYDRIDE lithium aluminum hydride to cold ethereal alumiSir: num chloride, or by adding allyl bromide in ether Lithium aluminum hydride attacks unsymmetri- to the standardized hydride solution prior to addically substituted epoxides predominantly a t the least tion of the epoxide. \Ye are presently studying the mechanism of the substituted carbon atom to give the more highly abnormal ring opening as well as extensions of the substituted alcohol. 1-3 Thus primary-secondary TABLE I REDUCTION OF EPOXIDES VITH LITHIUXALUMISPM HYDRIDE Entry compound
1 Propylene oxide 2 Propylene oxide 3 1,2-Epoxydecane 4 Styrene oxide 5 Styrene oxide 6 Styrene oxide 7 Styrene oxide 8 Isobutylene oxide 9 Isobutylene oxide 10 1,l-Diphenylethylene oxide 11 1,l-Diphenylethylene oxide 12 1,1,2-Triphenylethylene oxide oxide 13 1,1.2-Triphenylethylene . . a This work. Aluminum chloride. material.
Ri
Ri
Me H H Me H H Oct H H Ph H H Ph H H Ph H H Ph H H Me Me H Me Me H Ph Ph H Ph Ph H Ph Ph Ph Ph Ph Ph Generated in situ from
epoxides (I, R1 = alkyl, R2 = R3 = H) give secondary alcohols (11, same), and primary-tertiary or secondary-tertiary epoxides (I, R 1 , R? = alkyl, Ra = H or alkyl) give tertiary alcohols (11,
Moles
Products
yo I11 Ref. Yo I1 100 0 a 0.3 0 60 ca. 20 a ca. 80 .25 I' ca. 42 0 2 100 .25 0 90 0 3 100 .25+ 0 94 90-95 a 5-10 .3 0 82 90-98 u 2-10 .25 lb 87 28 a 71 1.5 c 80 2-5 a 95-98 0.3 0 26 93-95 a 5-7 .25 lb 55 100 0 a .4 0 97 86 a 14 2.4 c 85 0 a 100 2,2 0 1l.jd 100 U 0 2.4 c 91 Also recovered 81% starting 1 mole of allyl bromide. LAH
Ra
AlXa
Yield, %
method to other epoxides, including alicyclic and steroid cases. This work is supported in part under Atomic Energy Commission contract AT(11-1)-38. (4) Shell Research Fellow, 1955-1956.
RIRzCHCHOHR~ +R'>C--C
