236%
NORMAN
L. ALLINGEKAND
was obtained from petroleum ether as white needles, 111.p. 76-76.5'. Anal. Calcd. for C16H180: C, 84.91; H, 8.02. Found: C, 84.66; H, 8.01. The compound gave chemical tests similar t o those obtained with the lower homologs. P-hfethoxyfluorene.--A diazonium chloride solution was prepared from 7.7 g. of 2-aminofluorene27 and was treated with 8 g. of zinc chloride. The resulting precipitates, dried in zlucuo, weighed 9.5 g. This complex salt was refluxed for 36 hours in 100 ml. of methanol. The resulting mixture was filtered while still warm and the filtrate cTlled yielding 5.5 g. (66%) of a white solid, m.p. 98-102 . Upon recrystallization this product melted at 106-108° (lit.27106108').
Macro Rings.
1. GR.4M
VOl. 76
2-Hydroxyfluorene.-A solution containing 1 g. of 2methoxyfluorene in a mixture of glacial acetic acid (20 ml.) and 48% hydrobromic acid (12 ml.) was refluxed for 36 hours. The phenolic material was separated from the reaction mixture in the usual way giving 0.5 g. (54%) of a cream-colored solid, m.p. 160-164". Recrystallization of this product from dilute acetic acid gave material melting a t 167-169" (lit.27sintering at 166", m.p. 168" uncor.). Biological Testing.-The testing procedure was essentially that of Leonard and Blackford.z Measurement was made of the inhibition of the rate of radial growth of test cultures of Aspergillus nigerS8caused by dispersion of known concentrations of the test compound in the agar medium. (28) T. C. 215-1217 Steinberg. We are indebted t o hlrs. Rita S. Kardon and Mrs. Barbara S. Bayless for carrying out these tests.
DURHAM, S.C.
(27) 0 D i d s , B e y . , 34, ii5S (1901).
[ C O N T R I B U T I O S FROM T H E
DONALD
DEPARTMENT OF
C H E M I S T R Y O F T H E c N I V E R S I T Y O F C A L I F O R N I A AT LOS A N G E L E S ]
IV. The Preparation of Three New Paracyclophanesl BY
?;ORMAN
L.
ALLINGER AND DONALD
J.
CRAM'
RECEIVED DECEMBER 15, 1953 The three pardcyclophanes ( I )with the 3- and 4-, 4- and 5-, and 5- and 5-membered methylene bridges have been prepared. These syntheses further illustrate the generality of the method involving hydrogenation of the benzene rings prior to an acyloin ring closure followed by dehydrogenation at a later stage. The stereochemistry of the fully hydrogenated pardcyclophanes is discussed.
The preceding paper in this seriesd reported the synthesis and properties of the paracyclophane (I) with n = ?n = 4. The acyloin ring closure fails on esters of the phenylacetic type," such as TI, but if
*
(CHZ)~
to give VII, and along with the other two homologous diketones was submitted to the modified Willgerodt r e a ~ t i o n . ~The resulting thiomorpholides were hydrolyzed to the corresponding acids which were subsequently esterified. The over-all yields of ester from diketone were satisfactory (40Ci070) except in the case of the unsymmetncal diketone, VII, which gave only a 15% yield of ester The aromatic rings were then hydrogenated to give the corresponding cyclohexyl compounds JX as cis-cis, cis-trans and trans-trans mixtures. The mixtures obtained were used directly in the acyloin ring c l o s ~ r e ,no ~ separation of isomers being attempted. Only one acyloin XB was obtained in a crystalline state, the others being isolated as oils which appeared to decompose appreciably when distilled. Therefore the crude acyloins were subjected directly i o a modified6 Clemmensen reduction followed by a catalytic reduction which converted olefinic by-product to the desired saturated material. The saturated hydrocarbon XIB ( n = 5, nz = 4) was obtained as a single pure compound in a yield of 19yo(based on diester IXB), which is comparable to that obtained in the previous preparation3 of the analogous substance with n = m = 4 (22Yo). The configuration of XIB was demonstrated to be cis-cis by its preparation from the parent paracyclophane (XIIB) by hydrogenation, a single isomer being obtained. Scale molecular models of XIB and XIIB indicate that neither can one ring of XIIB turn to right angles to the other ring nor is there room in between the two rings for catalyst with its absorbed hydrogen. The same considerations apply to the partially reduced intermediates in XIIB ---t XIB. Therefore XIB must possess the cis-cis
---c _.
--CH?COOCHa
(CI li i l
the benzene rings of I1 are hydrogenated, the resulting dicyclohexyl compounds can be closed to give an acyloin ultimately convertible to I with n = m = 4. The method is obviously applicable to the synthesis of compounds having methylene bridges of this size or larger, but smaller only to the limit where steric factors prohibit ring closure. I n the previously reported synthesis of I with n = m = 4,the saturated ester I11 underwent acyloin ring closure only if the groups on the cyclohexane rings were oriented cis-cis, polymer resulting from starting materials of other configurations.
In the present investigation three new paracyclophanes were prepared by the general sequence formulated. The appropriate hydrocarbon I V was acetylated to give the corresponding diketone V, and in one case a mixture of the mono- and diketone ( n = 5 ) . This monoketone VI was propionylated (1) This work u a s sponsored by the Office of Naval Research (2) Requests for reprints should be addressed to this author (3) D. J. Cram and N L Allinger THIS J O I J R ~ A L .76, 726 (1954) ( 4 ) D J Cram and I1 5twnberg tbrd , 1 3 , i n 9 1 (1951)
( 5 ) E Schmenk and D Papa J 0 , g Chenz , 11, 798 (1946). (6) K Wiesner, D. M. MacDonald, R R Ingram and R B Kelly, Cmiriidirin J Ker B28, X I ( l U i 0 )
PREPtIRATION O F T H R E E N E W PARA~CYCLOPHANES
May 5, 1954
2363
bon obtained melted over a 50" range. (2) This (CHi), 0 material was dehvdro0 -+ (CH,),, AIC13 genated to the bar,h>-C-CHj cyclophane (XIIC) in IL < ll 957* yield (the product 0 melted over a 1.5" range) VI VA, n = 3 IVA, n = 3 (3) Fractional crystalliB.n = 5 B,n = 5 zation of the saturated PnOJ A1CL hydrocarbon gave two -C-CH3 sharply melting sub-O-CH~-COOCHJ 1, Morpholine, S stances, m.p. 140.5" and 2, OH-, HzO (CH2)n a (CHZ)~ 0 m.p. 82.6", both of which -- .>-C-CHn--CH1 gave the correct analysis 11 for XIC. A mixed melting point of these sub0 stances did not give a de111 VIIIA, n = 3 and x = 1 pression, and therefore B,n = 5andx = 1 C,n = 5andx = 2 the higher melting compound is presumed to be H,JPt a pure component, and _the other a eutectic mix&-' CH,-COOCH, [ - < ~ - ) - c H ' ~ c = o ture of the higher melt1, Na xylene (CHs), (CHzh I ing compound and a sec2, AcOH /CHOH ond isomer. (4) CataCH2 ),-COOCHI l--(cHLjz lytic reduction of paraXA, n = 3 and x = 1 cyclophane X I I C gave a IXA, n = 3 and x = 1 B,n = 5andx = 1 B, n = 5 and x = 1 crystalline mixture of C,n = 5 a n d x = 2 C,n=5andx=2 fully hydrogenated hydrocarbons whose melts/,AcOH ing point was slightly raised by admixture with --& the above material meltr-( A - 7 \ - _ _ / 'I Pd ing a t 140.5". (CHz),, (CHI),, t (CH?j,, ( CH2 The above results are I - H2 L-(T\>-J rationalized as follows : \ L J Two types of isomerism XIIA, n = 3 and m = 4 M A , TZ = 3 and ?n = 4 are possible with comB, n = 5 and m = 4 B,n = 5andm = 4 pounds of general strucC,n = 5andm = 5 C, n = 5 and nt = 5 ture X I , that due to the geometry, and if the rings cannot turn over, the relative configurations of the points of attachment configuration is probably that of XI'B. The yield of the methylene bridges to the cyclohexane rings, from ester (IXA) of the saturated hydrocarbon, and that due to the restricted rotation of the two XIA ( n = 3, m = 4), amounted to only 67,) a fact rings with respect to one another. Scale molecular compatible with the more constrained geometry of models suggest that the latter type of isomerism this cycle. Here the cis-cis structure possessing might be possible in XI with n = m = 4 or n = 4, rn = 5 , but that the rings can probably turn over in H H X I with n = m = 5 . Therefore it is probable that ]--? the mixture of isomers obtained both by ring cloI HL (CHL)~ (CHih4 + (CHJ,, (CH?)m sure and by reduction are of the cis-trans type. This conclusion means that in the course of the reducI -, / L /--I I Pt I of the two aromatic rings, either catalyst with tion L-L>-L its absorbed hydrogen had to get between the two H H rings, or that one ring had to turn over with respect XIIA, n = 3 and rn = 4 XI'A, n = 3 and m = 4 B,n = 5andm = 4 B , n = 5 a n d m = 4 to the other a t some point in the course of the reduction (formula XI11 illustrates one possible situathe rotational configuration of XI'A is assumed by tion). Since the space between the rings is rather analogy with XIIB + XI'B, and with the com- constricted, the latter explanation is more compatpound having n = m = 4.3 Both XIA and XIB readily underwent dehydrogenation, with palladium to give XIIA and XIIB, respectively. I n the case of hydrocarbon X I C (n = m = 5) a new situation was encountered. The yield of this material based on diester is sufficiently high (477,) that ring closure of more than the cis-cis diester I X C is indicated. This contention is supported by the following additional facts: (1) The hydrocarr-rC>-C-CHd
Acz0
+
L--(T-
11
r-c L-
