This dissertation has been microfilmed exactly as received 66-15,089 GAUGE, Wilbur Seth, 1938- TEE SYNTEESIS OF 3-(l-NAPETEYL-4-PEENANTERYL- METEYL)GLUTARIC ACID: A POTENTIAL INTERMED IATE FOR EEPTAEELICENE.
The Ohio State University, Ph.D., 1966 Chemistry, organic
University Microfilms, Inc., Ann Arbor, Michigan THE SYNTHESIS OF 3-(1-KAPHTHÏL-4-PHENANTHRYIMETHÏL)-
GLUTARIC ACID* A POTENTIAL INTERMEDIATE
FOR HEPTAHELICENE
DISSERTATION
Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University
By W ilbur Seth Gaugh, B. A.
*******
The Ohio State University 1966
Approved by
Adviser Department of Chemistry ACKNOWIEDGMENTS
It is with sincere pleasure that I express ray appreciation and gratitude to Dr. Melvin S. Newman for suggesting this problem, for his counseling and unfailing encouragement and for his personal friendship.
i i VITA
September 13, 1938 Born - Sharon, Pennsylvania i 9 6 0 ...... B.A., Thiel College, Greenville, Pennsylvania
1 9 6 0 -1 9 6 1 ...... Teaching Assistant, Department of Cnenistry, The Ohio State University, Columbus, Ohio
1961-p re se n t , . . Research Feillow, Department of Chemistry, The Ohio State l&iiversity, Columbus, Ohio
PUBLICATIONS
Effect of the alkali cation upon the rate of the Benzilic acid rearrange ment, W. H. Puterbaugh and W. S, Gaugh, J, Org, Chera. 3513-15 (1961).
FIELDS OF STUDY
Major Field : Organic Chemistry
Studies in Advanced Organic Chemistry, Professors Melvin S, Newman, Harold Shechter, Michael Cava, William White and Richard Finnegan
Studies in Advanced Inorganic Chemistry, Professor Sheldon Shore
Studies in Kinetics, Professor Frank Verhoek
Studies in Thermodynamics, Professor George Macwood
Studies in Photochemistry, Professor Jack G, Calvert
Studies in Radiochemistry, Professor Thomas Sweet
i l l CONTENTS
Page
ACKNOWLEDGMENTS...... i l
VITA . ill
INTRODUCTION AND HISTORICAL...... 1
STATEMENT OF THE PROBLEM ...... 9
GENERAL...... 10
The s y n t h e s i s ...... 10
DISCUSSION OF RESULTS ...... 15
EXPERIMENTAL...... 25 ■X-2“( 5 . 6, 7,8-tetrahydronaphthoyl)propionic acid ( l ) ...... 25 •y"-2-( 5 ,6 , 7, 8-tetrahydronaphthyl)butyrio acid ( I I ) ...... 26 Methyl y-2-(5, 6,7 , 8-tetrahydronaphthyl)butyrate (III) .... 27 Methyl 9^(2-naphthyl )butyrate (IV ) ...... 27 X-(2-Naphthyl)butyric acid (V ) ...... 28 4-Oxo-l,2,3,4-te trahydrophenanthrene ( V I ) ...... 28 1,2-Dihydro-4-methylphenanthrene (VII) ...... 29 4-Methylphenanthrene (VIII) ...... 30 4-Phenanthroio acid (IX ) ...... 31 Methyl 4-phenanthroate ...... 32 h-Phenanthrylmethanol ( X ) ...... 32 4-Phenanthraldehyde (XI) ...... 33 Dimethyl "^-4-phenanthralmalonate (XII) ...... 3^ Ethyl =C-cyano-4-phenanthrylacrylate (XIV) ...... 35 Isopropylidene m alonate ...... 35 Isopropylidene 4-phenanthralmalonate (XIII) 36 Ethyl «C-cyano-<9-l-naphthyl- (3 -4-phenanthrylpropionate (XV) . 36 «c-Cyano-<3 - 1-naphthyl-^ -4-phenanthrylpropioni o acid (XVI ) . 37 ^ -1-naphthyl- -4-phenanthrylpropioni c acid (X V II) ...... 38 Methyl -1-naphthyl- (9 -4-phenanthrylpropionate ...... 39 ^ -(Aminomethyl)-y-l-naphthyl-y-4-phenanthrylpropanol CtVIIl) 39 2-(l-N aphthyl-4-phenanthrylm ethyl)-l,3-ppopanediol (XIX) . . . 40 3-(l-naphthyl-4-phenanthrylmethyl)glutario acid (XX) . . . . 41
iv ILLUSTRATIONS
Figure Page
1 11
2 14
3 18
4 20
5 24
Table
1. Reaction of XV ...... 21 INTRODUCTION AND HISTORICAL
Compounds that can exist in optically active forms but possess no asymmetric carbon atom have long been of interest to chemists.
Examples of this type of molecules are the aliénés, I, spiranes, II, and molecules which owe th eir asymmetry to restricted rotation about a single bond.
'C = C = C ^ C = c = c
n
The ortho-substituted biphenyls. III, make up the most familiar
example of the last mentioned case. If the R groups are bulky enough,
the interconversion of the two enantiomorphs by the "slipping past" of
hindering groups may be of an energy barrier high enough to allow
resolution into optically active forms.
1 lE I
Various workers have attempted to determine whether an optically active biphenyl would retain i t s asymmetry when two of the rotation hindering groups were connected in a ring. The optically active diol, IV, yielded the ether, V, as an optically active compound, but ring closure of IV gave the hydrocarbon, VI, as an optically inactive product.
Racemization under the cy cliza tio n conditions was deemed unlikely.^
Similarly, the ring closure of resolved 2,2'-diamino-6,6'-dimethyIbiphenyl yielded only optically inactive l,10-dimethylbenzo[c]cinnoline (VII ).^ The diamino derivative of this compound, VIII, has, however, been resolved
subsequently by conventional procedures,^
Another example of a successful transformation of a biphenyl
type compound to its cyclic analog is the synthesis of optically active
9,10-dihydrodibenzo[o,g]phenanthrene (X) from a resolved sample of the
acid, IX.^
^G. W ittig and H. P e tr i, Ann., 506. 25 (1935). 2 G. Wittig and 0. Stichnath, Ber., 68, 928 (1935).
Thielacker and F, Baxman, Ann., 581. 11? (1953). 4 D. M, Hall and E. T. Turner, Chemistry and Industry, 1177 (1953). C^gOH CH3O CH3O 0^2 COLOH C H ,0
3ZI
Hg CO.H H,
3 m .; R =H
3Zm ; R=NHa
The observation was made^ in 1940 that molecules containing the
4,5-dimethylphenanthrene system (XI) might be capable of optical resolvt- tion because of the interference of the methyl groups in the hindered positions. Three alternatives were suggested relative to the geometry of
S. Newman, J , Am. Chem. Soc,, te , 2295 (1940). the molecule as a whole in this type of system: "(l) the methyl groups lie bent away from each other but in the same plane as the aromatic rings ;
(2 ) the aromatic rings are distorted in some way; ( 3 ) the methyl groups are bent out of the plane of the aromatic rings." If the first alterna tive is correct the molecule would contain a plane of symmetry and hence would not be capable of optical activity. However, if the second or third alternative, or a combination of the two, were correct, the molecule would contain no element of symmetry and thus should be capable of resolution. The work which followed this prediction has been reviewed previously,^3 and will therefore be discussed only briefly.
Y
XE
That case (1) does not describe the geometry in this type of molecule has been demonstrated by the successful resolution of 4,3, 8-trimethylphenan-
thrylacetic acid (XII),^ 4-(1-methylbenzo[c]phenanthryl)acetic acid
1R. M. Wise, Ph.D. dissertation, Ohio State University, 1955.
D. Lednicer, Ph.D. dissertation, Ohio State University, 1955.
^H. Gerry, Ph.D. dissertation, Ohio State University, 1964. 4 M, S. Newman and A. S, Hussey, J . Am. Chera. Soc., §2 , 3023 (194?). (XIII),^ 4 ',4“,6 ', 6" - t 0tram eth y l- 3.^ i5 t 6-dibenzphenanthrene- 9,lO - g dioarboxyllic acid (XIV), and the previously mentioned cinnoline, VIII.
H3C.
CH, CH. CH.
HO^C-HgC V CHgCOgH SU % n i
COgH
COgH f I
"YTV
1M. S. Newman and W. B. Wheatley, J. Am. Chem. Soc., 20, 1913 (1946). ^F. Bell and D. H. Waring, J. Chem. S oc., 2689 (1949). Molecules showing this type of optical activity which contain no methyl groups have also been synthesized and resolved: e.g., 3 ,4 ,5 ,6 - dibenzphenanthrene-9,10-dicarboxylic acid^ (XV) and 9,10-dihydrodibenzo-
[o,g]phenanthrene (X) already discussed.
3 3 T
The synthesis and resolution of phenanthro[3,4-c]phenanthrene 3 ii ("hexahelicene") (XVI) demonstrated that disymmetry due to intra molecular overcrowding can be caused by a warping of the ordinarily
planar aromatic system.
1,The term adopted for this type of optical activity is "optical activity due to intramolecular overcrowding." Reference 2. ^F. Bell and D. H. Waring, Chemistry and Industry, 321 (1949). The optical activity was shown only by the racemization of the morphine s a l t . The fre e acid obtained showed no a c tiv ity . ^D. Lednicer, Ph.D. dissertation, Ohio State University (1955)« ^M. S. Newman and D. Lednicer, J. Am. Chem. Soc., 28 , 4765 (1956). The x-ray orystallograph!o investigation of benzo[c]phenanthrene
(XVII), and pentahelicene (XVIII) have shown these molecules to be non- planar, but with no severe localized buckling. The carbon atoms of each ring are roughly co-planar, and the warping is distributed evenly throughout the entire aromatic system. Neither of these compounds has yet been resolved.
xa z
Theoretical calculations of the optical rotary dispersion of hexahelicene have been performed independently by two groups. While the results of these studies are substantially in agreement about the magni tude of rotation at the D-line of sodium, the sign of the calculated 3 rotations do not agree. Fitts and Kirkwood calculated that the
[R]-hexahelicene (the left-handed helicene)^'^ is the levorotary isomer;
^F. H. Herbstein and G. M. J. Schmidt, J. Chem. Soc., 3302 (195^)' 2 A. McIntosh, J. Monteath Robertson, and V. Vand, J. Chem. Soc., 1661 (1954).
3d . Fitts and J. Kirkwood, J. Am. Chera. Soc., 22» 4940 (1955). Cahn, C. Ingold, and V. Prelog, Experentia, 12, 81 (1956).
^R. Cahn, J. Chem. Ed., 41, 116 (1964), however, M oscowitz^calculated that the levorotatory isomer was [S]-hexahelicene (the right-handed isomer). Determination of the sign of rotation of hexahelicene of known configuration therefore became a matter of increased interest.
In an attempt to resolve this problem, the substituted hexa- 3 helicenes shown below have recently been synthesized.
(IXa) R = CH^ (iXd) R = NHg
(iXb) R = CO2H (He) R = I,
(iXc) R = COgCH^
The resolution and x-ray analysis of 7-iodohexahelicene (IXe) are
currently under investigation.
^A. J, Moscowitz, Ph.D, dissertation, Harward University, 1957.
^A, Moscowitz, Tetrahedron, l^* (I 96I),
Gerry, Ph.D, dissertation, Ohio State University, 1964, STATEMENT OF THE PROBLEM
The objective of this study was to determine whether the synthetic scheme utilized by Lednicer for the preparation of hexahelicene could be modified to prepare the next higher member of the series, heptahelicene. GENERAL
(a ) The synthesis
The various routes which have been used successfully for the synthesis of dibenzo[c,g]phenanthrene and 1,IR-dimethylbenzo[c]- phenanthrene, and hence which might prove adaptable to the synthesis of 1 2 3 ^ helicene-type compounds, have been reviewed by previous workers. ' ’ ’
These reviews will not be repeated here. The synthetic scheme^ which was utilized successfully for hexahelicene and the substituted hexahelicenes mentioned previously was adopted for this work. The reaction sequence, in general form, as applied to hexahelicene is shown in Figure 1.
The preparation of the malonic ester. I, is the key to the entire reaction scheme. -In order to modify this synthesis to obtain the hepa- helicene system, there are two methods by which the required malonic exter corresponding to I might be prepared.
^D. Lednicer, Ph.D. dissertation, Ohio State University, 1955« ^R. Wise, Ph.D. dissertation, Ohio State University, 1955.
% . Wolf, Ph.D. dissertation, Ohio State University, 1951.
^A. Kosak, Ph.D. dissertation, Ohio State University, 1948.
^This general scheme was first reported by M. S. Newman and L. H. Jo sh el, J . Am. Chem. Soc., 485 (1938).
10 il
/N N — MgBr CH N — CH 0 — **■ N 1 CH CH = 0 ( 002083)2 HgCOgC COgCHj
N N \ / CH
CH /\ HO-HgC COgCHg
0 HO2 C
N
Fi g u r e" I 12
N -M g B r P - C H = C(COpCH,)„ (0)
CO^CHj
COXH
N-CH = C(C0pCH3)p (b) P-MgBr
Scheme (b), however, requires use of the Grignard reagent derived from a ^halophenanthrene. Since none of the 4-halophenanthrene s had then been synthesized,^ scheme (a) was chosen for the in itial synthetic attem pt.
The 4-phenanthraldehyde (XI) required in scheme (a) had been prepared by Rutherford^ from ^phenanthroic acid (IX) via the Rosenmund reduction of the corresponding acid chloride. Collins^ subsequently studied the synthesis of IX and concluded that optimum yields of this
The synthesis of ^bromophenanthrene has recently been achieved in this laboratory. R. Darlak and E. Zuech, unpublished Research Reports, Ohio State University, I 965. O K. G. Rutherford, unpublished Research Report, Ohio State diversity, 1957. 3 D. J. Collins, unpublished Research Report, Ohio State University, 1959. 13 compo\md were achieved by the reaction sequence shown in Figure 2,
Furthermore, 4-phenanthraldehyde had been shown ' to react with dimethylmalonate and ethyl cyanoacetate to yield XII and XIII,
Preliminary studies on the Grignard reactions of XII and XIII 1 2 with 1-naphthylmagnesiura bromide had been attempted; ’ however, lack
sufficient material made reinvestigation of this reaction necessary.
^K, G, Rutherford, unpublished Research Report, Ohio State University, 1957. p E, Kochendorfer, unpublished Research Report, Ohio State University, i 960. 14
Zn/Hg
FeCI HCI 0 ^ ? ' OH OH XL CH.OH KOI
I.) PCI, Pd/C A
2 )S nC l4 2)K0H OCH: XZ , R = 0CH3 nr
T , R = OH
Pd/C
CH CH
3ZI IDXT KgCtgO^
CrO LiAIH4 o -
C H = 0 CHgOH
X L X
Figure 2 DISCUSSION OF RESULTS
The large-scale (ça. 2 moles) Friedel-Crafts reaction of tetralin
■with succinic anhydride proceeded smoothly to give the keto-acid. I, in y ie ld s o f 8 8 -9 ^ . The Clemmensen reduction of th is compound gave
uniformly high yields of X -(2-tetralyl)butyric acid (II). Estérifica
tion of the latter by hydrogen chloride in methanol gave the methyl
ester. III, (94-96^), which upon dehydrogenation with 10^ palladium-
charcoal at 280-300° gave the corresponding naphthalene derivative, IV,
in 97^ yield. Attempts to run the dehydrogenation reaction in larger than 50.0 g. batches resulted in much lower yields. Hydrolysis of IV gave almost quantitative yields of 7^(2-naphthyl)*
butyric acid (V), Cyclization of this acid in liquid hydrogen fluoride
gave only about 70^ of the ketone, VI, as a crude reaction product. How
ever, the acid chloride of V was readily cyclized to the ketone by brief
treatment (2 .5 min.) with fuming stannic chloride.
The reaction of VI with méthylmagnésium bromide followed by
subsequent acidic dehydration of the intermediate carbinol gave 91^ of
1 ,2-dihydro-4-methylphenanthrene (VII).
Dehydrogenation of VII in 50.0 g. batches with 10^ palladium-
charcoal at 300-320° gave a 95^ yield of 4-methylphenanthrene (VIIl).
Oxidation o f VIII with aqueous sodium dichromate in a rocking bomb at
250 ° for 30 hours gave 84-88^ of 4-phenanthroic acid (IX ). ^ The
^L. Friedman, D. L. F ish el, and H. Shechter, J. Org. Chem., 20» 1453 (1965). 15 16 bulk of the reaction mixture consisted of unreacted starting material which could be recovered.
Preparation of h-phenanthraldehyde (XI) from the acid chloride of
IX via the Rossenmund reduction was unsatisfactory for preparative pur poses. Although yields of up to 85^ were obtained in this reaction, more often less than 20^ of the product could be realized. The low yields observed for this reaction are not surprising since 4-phenanthraldehyde decarbonylates quantitatively if subjected to the reaction conditions overnight. Attempts to prepare the aldehyde by selective reduction of the acid chloride with lithium tri-t-butoxyaluminohydride failed.
Reduction of either 4-phenanthroic acid or its corresponding methyl ester with lithium aluminum hydride gave essentially identical yields (93-96^) of the carbinol, X,^ It is worth noting that methyl 4-phenanthroate could be readily prepared in quantitative yields by the use of diazomethane as reported in the experimental section. The reaction of methanol with the corresponding acid chloride also gave the ester in high yields. However, attempted estérification of IX by prolonged refluxing in methanol which had been saturated with hydrogen chloride gas resulted in decarboxylation of the acid and recovery of phenanthrene.
This reaction may be analogous to the decarboxylation of 2,4,6-trimethyl- benzoic acid and other highly hindered acids studied by Schubert and
"*R. J. C. Fierens, R. H. Martin, and J. Van Ruppleberg, Helv, Chim. Acta., ]8, 2003 (1955). The above authors report preparation of the carbinol from 4- methylphenanthrene via bromination to the bromomethyl compound, treatment with sodium acetate, and hydrolysis to proceed in 86^ yield. However, several attempts to utilize this procedure resulted in yield of about 50 ^. 17 co-workers. The selective oxidation of X with the complex of pyridine- chromium trioxide finally gave the aldehyde, XI, in reproducible yields of 83-88^.
The condensation reactions of the aldehyde proceeded smoothly with each of the following reagents to give the yields indicated: dimethylmalonate (71-7^^). isopropylidenemalonate (65-70/5), and ethyl cyanoacetate (86-90$5) (Figure 3 ). The subsequent G rignard re a ctio n s on these compounds, however, presented the first obstacle in the problem.
In the synthesis of hexahelicene, the 1,4-addition of 1-naphthyl- magnesium bromide to the ester corresponding to XII constituted one of the weakest links in the synthetic chain, as yields ranged from 18.2^ to
55.9/5, and averaged less than 4-0^.^ However, subsequent work on this reaction^ resulted in raising the yields to 70-72^. It was also reported that the 1,4-addition to the cyano-ester corresponding to XIV proceeded in reproducible yields of 85^, but that all attempts to hydrolyze the product to the corresponding malonic acid resulted in decarboxylation to the propionic acid.3 In view of these results it was clearly preferable to obtain the Grignard product from either XII or XIII, and thereby avoid any problems arising from hydrolysis.
An extensive study of the Grignard reaction on XII and XIII, however, failed to yield the desired products. During this study more
1 W. M. Schubert, Jere Donahue, and J. D. Garner, J. Am. Chem. Soc., 2 6, 9 (1954).
2D. Lednicer, Ph.D. dissertation, Ohio State University, 1955.
^H. Gerry, Ph.D. dissertation, Ohio State University, 1966. 18
C = 0
CH, CH CN
COXH. CH. '3 '3 C = C ,C = C CN '3 '3
MgBr MgBr MgBr
CH^COjCHj qH/ COjCHj CH CH \ O j C H 3 ^C N Z2T Figure 3 19 than thirty reactions were run on each of the compounds without success. 1 Reactions were run in ether, benzene, tetrahydrofuran, tetramethylurea, and combinations of those solvents. Attempts were made with an excess of magnesium bromide present, with cuprous chloride added, and with sublimed magnesium3 in some cases and non-sublimed magnesium in others. Reactions were run using both normal and inverse additions, and over a temperature
range of -20° to 100°. Under milder conditions only starting material
was obtained, whereas with forcing conditions mixtures of starting
material and 1,2-addition products resulted.
In direct contrast to these results, the 1,4^addition of
1-naphthylmagnesiura bromide to the cyano-ester, XIV, gave the desired
product, XV, in yields of 60-70^. Subsequent attempts to convert this
product to the desired malonic acid derivative are summarized in Figure 4
and Table 1.
Hydrolysis of the cyano-ester, XV, with potassium hydroxide in
refluxing methanol for 6 hours gave a nearly quantitative yield of the
corresponding cyano-acid, XVI. However, if the reaction was allowed to
run for 3 days, a mixture of XVI and the propionic acid, XVII, resulted.
Similarly, refluxing XV in potassium hydroxide-ethylene glycol for 6
hours gave a high yield of XVII.
Attempts to utilize the greater nucleophilicity^ of the peroxide ion for the hydrolysis were also unsuccessful. Treatment of XV with
The suggestion to attempt the reaction in tetramethylurea was made by several research chemists at E. I. DuPont de Nemours as a result of successful experience with this solvent. ^The author wishes to express his gratitude to the Dow Chemical Co. for a generous sample of sublimed magnesium. 3 K. B. Wiberg, J. Am. Chem. Soc., 2Z» 2519 (1955). 2 0 P
KOH/ CH3OH (6 hrs.) I COgH 23Zr P \ / N KOH/CH OH (3 days) 3 CH I KOH / Ethylene glycol CM 2s COgH 23ZH H2SO4 / CH3CO2 H
p . ,N H2O2 /O H " (5 0 ° ) % - _ - m z l^COgC CN
H2O2 / OH (room temp. )
H C I / CH^OH
I) CH 3 CH2 OH/H + i c s m . N.R. 2)8" EtO-CO-CO-OEt
Figure 4 TABLE 1
Reactions of XV
Type Reagent Solvent Time Temp. Product Found Y ield
H ydrolysis H2SO4 CHgCOgH 8 hours 60° XVII > 90^
Hydrolysis KOH CH3OH 6 hours Reflux XVI 90^
Hydrolysis KOH CH3OH 3 days Reflux XVI and XVII 85^
Hydrolysis KOH Ethylene 7 hours Reflux XVII 92$ glycol
H ydrolysis H^Og/NaOH Ether-benzene 7 days Rm. temp. Starting material — —
H ydrolysis HgOg/NaOH Benzene 3 hours 50 ° XVII 60^ A1coholysis EtOH/HCl Ether-benzene 14 days IQO Starting material --
A1COholysis EtOH/BEo Ether-benzene 14 days 10° Starting material ——
A1coholysis EtOH/HCl 18 days Rm. temp. Starting material --
A1coholysis EtOH/HCl Sulfolane 18 days Rm. temp. Starting material — —
A1coholysis EtOH/BF^ Sulfolane 18 days Rm. temp. Starting material --- 22 sodium hydrogen peroxide fo r 1 week a t room tem perature gave nearly quantitative recovery of starting material. The same reaction at 50° for 3 hours, however, gave ca. 60^ of the propionic acid, XVII. One attempt at acidic hydrolysis using a sulfuric acid-acetic acid medium also gave XVII.
Several attempts were made to convert the cyano-ester to its corresponding imino-ester hydrochloride by alcoholysis. This reaction was attempted for periods up to 18 days in ether-benzene, carbon tetrachloride-benzene, and sulfolane; either anhydrous hydrogen chloride or boron trifluoride was used as a catalyst. In all cases only starting material was obtained.
Attempts were made to convert the propionic acid, XVII, to the desired malonic ester via the reactions shown in Figure 4. Estérification of XV with ethanol gave the corresponding ester in 95^ yield. Conversion of this ester to its anion was accomplished with either sodium ethoxide or triphenylmethyl sodium. (That the desired anion was indeed formed with the latter base is confirmed by the characteristic color change from blood red to yellow.) However, addition of diethyl carbonate, diethyl oxalate, or ethyl chloroformate all resulted in isolation of starting material. Presumably, steric factors prevented the introduction of an additional carbomethoxy group into this system, and the anion was destroyed in the subsequent work-up.
The re a c tio n scheme shown in Figure 5 f in a lly provided th e ro u te to desired products. Reduction of the cyano-ester, XV, with lithium aluminum hydride gave the corresponding amino-alcohol, XVIII, in 86^ yield. Diazotization of this compound resulted in a 32-38# yield of the li3-propanediol (XIX). That this is the desired product and not a diol 23 resulting from skeletal rearrangement was shown by analysis of its nuclear magnetic resonance spectrum. The bis-homologation of XIX to give the g lu ta ric acid , XX, was accomplished as shown w ithout is o la tio n of the intermediates in ça. 70$ overall yield. The subsequent ring closures of XX to give the heptahelicene skeleton were not attempted because of insufficient materials at this time. It is, however, believed that synthesis of the glutaric acid represents a definite breakthrough toward the ultimate synthesis of heptahelicene. Work is presently being continued toward this goal. 24
LiAIH4
CH^CHgNHg CH COgCgHg ^C H gO H T g m
HNCL
ncH ^O gC i 2) KCN ^3) KOH CO_H CHJDH
CHgOH
3 3 L X T X l
Figure 5 EXPERIMENTAL
Generalizations
All melting points were determined on a Fisher-Johns melting point apparatus and are uncorrected.
The analyses were determined by Micro-analysis, Inc., Wilmington,
Delaware.
Infrared spectra were recorded on a Ferkin-Elmer Infracord
Spectrometer.
The phrase "worked up as usual" means that the organic solutions iTOre washed twice with water or until neutral to litmus paper, and then washed with saturated sodium chloride solution and filtered through anhydrous magnesium sulfate. Skellysolves are petroleum fractions designated as follows ;
Skellysolve F, b.p. 35-55°
Skellysolve B, b.p. 60-68°
~ y -2-(5.6.7.8-tetrahydronaphthoyl)- propionic acid (I)
To 1200 ml. of thiophene-free benzene was added 200.0 (1.50 moles)
of 1,2,3,4-tetrahydronaphthalena and 100.0 g. (l.O mole) of succinic
anhydride. The solution was vigorously stirred and 293.7 g. (2.20 moles)
of anhydrous aluminum chloride was added through a Gooch tube over a
45-min. period. The reaction mixture was then heated on a steam bath for
3 hr, at which time evolution of hydrogen chloride had nearly ceased.
25 2 6
The flask was cooled in an ice bath, and chipped ice was added to the re a c tio n m ixture u n til no re a ctio n was n o tic e ab le . Hydrolysis was then completed by the addition of 400 ml. of 6 N hydrochloric acid. The benzene was removed by steam distillation and the resultant suspension was allowed to cool to room temperature with frequent shaking.
The aqueous layer was decanted and the solid was dissolved in
1200 ml, of 15^ potassium carbonate solution. Steam was passed through the resultant solution for 15-20 min., and the insoluble aluminum salts were removed by filtration. The filtrate was acidified with cold 6 N hydrochloric acid to give 186.9 g. ( 89. 6#) of light tan solid, m.p.
109-113°. Recrystallization from benzene gave colorless needles, m.p.
112-114° (lit. m.p. 114-116°).1
' y - 2- ( 5 .6 .7 . 8- te trahydronaphthyl)butvri c acid ( I I )
By u tiliz a tio n o f the M artin M odification o f the Clemmensen
Reduction,2 II was prepared as follows:
A mixture of 450.0 g. of mossy zinc, 45.0 g. of mercuric chloride,
25 ml. of 12 N hydrochloric acid and 750 ml. of water was shaken
Vigorously for 10 min. The liquid was decanted, and to the freshly
prepared zinc-amalgam were added 350 ml. of water, 825 ml. of 12 N hydro
chloric acid, 450 ml, of toluene, 12 ml. of glacial acetic acid, and
186.9 g. of crude I. The reaction was refluxed vigorously for 48 hr.
M. S. Newman and H, V, Zahm, J . Am. Chem. Soc., 1097-1101 (1947). m. L. Martin, J. Am. Chem, Soc., j8, 1438 (I936), 27
After cooling, the layers were separated, and the aqueous layer was extracted twice with 50-ml. portions of benzene. The organic portions were combined and worked up as usual. The solvent was removed, and the
product was distilled to yield 167.3 g. (95.^) of II, m.p. 44-46°, b.p.
211-2l6®/8-9 mm. (lit. m.p. 47-49°, b.p. 195-200°/4.5-5 mm.)."*
Methyl 7^-2-(5.6.7.8-tetrahvdronaphthvl)- butvrate (III.)
Methanol (2.5 1.) was cooled in an ice bath and saturated with
anhydrous hydrogen chloride. To the resultant solution was added 218.0 g.
(0.87 mole) of II and the mixture was refluxed 18 hr. After cooling, the lower ester layer was separated, and the methanol layer was^concentrated
under reduced pressure to ça. I 50 ml., cooled and diluted with 800 m l. of
water. The resultant aqueous phase was extracted twice with 200 ml. of
benzene and the ester phases were combined. The organic phase was washed
three times with 100-ml, portions of. 10^ potassium bicarbonate solution
and worked up as usual. D istillation of the residue gave 223.4 g. (96.4^)
of a colorless oil, b.p. 142-148°/l.5 mm. (lit. b.p. 181-184°/3.5 -4 mm.).^
Methyl ‘^-(2-naphthvl)butvrate (IV)
The dehydrogenation apparatus utilized throughout the synthesis
consisted of six 125 ml. Erlenmeyer flasks connected via ground-glass
joints to a “cow," which was in turn attached to a reflux condenser. In
this fashion it was possible to dehydrogenate six 50 g. runs
simultaneously.
^M. S. Newman and H. V. Zahm, J. Am. Chem. Soc., 1097-1101 (1947). 28
To each of the flasks described above was added 50.0 g. (a total o f 1.29 moles) of freshly distilled III and 300 mg. of 10^ palladiura-
charcoal catalyst. The resultant mixture was heated in a salt bath at 280-310°. At the end of 3 h r ., 98^ of the theoretical amount of hydrogen had been evolved. After cooling, the catalyst was removed by filtration
and the product was distilled to give 2?6.5 g. (96.2^) of IV, b.p. 162- l64°/2 mm.).
y*-(2-Naphthvl)butvric acid (V)
A mixture of 275.0 g. (1.205 moles) of IV in 1.5 1. of ICf^ V 'T#* methanolic potassium hydroxide was refluxed for 2 hr. The methanol was then removed by distillation. After each 250-ml. portion of methanol was removed it was replaced by water. When virtually all the methanol had been replaced, the solution was cooled and washed twice with 200-ml.
p o rtio n s of benzene. The aqueous phase was then added to 800 m l. o f 6 N
hydrochloric a c id . The re s u lta n t idiite p re c ip ita te was co llected and
dried to give 258.0 g. (97^) of 7^-(2-naphthyl)butyric acid, m.p. 98-99°
(lit. m.p. 95-98°).1
4-0xo-1.2.3.4-tetrahvdronhenanthrene (VI)
A solution of 107 g. (0.50 mole) of V in 350 ml. of thiophene-free
benzene was prepared, and 100 ml. of the solvent was distilled to remove
traces of moisture. The cooled solution was diluted with 250 ml. of
anhydrous ether. To the resultant solution cooled in an ice bath 105 g.
(0.505 mole) of phosphorus pentachloride was gradually added. After
stirring for an additional 0,5 hr,, 3OO ml. of solvent was removed by
^M. S. Newman and H. V, Zahm, J. Am. Chem. Soc., 1097-1101 (1947). 2 9 distillation. After cooling, the solution of acid chloride was diluted to 1,25 1. with cold, dry thiophene-free benzene, and 60 ml. of fuming
stannic chloride was added in one portion with vigorous stirring. The reaction was allowed to proceed with rapid stirring for 2.5 min.; then a
solution of 250 g. of ice and 200 ml. of 12 N hydrochloric acid was added. After stirring an additional 10 min., two phases resulted. The organic phase together with a benzene extract of the aqueous phase was
washed twice with 200-ral. portions of water, and three times with 100-m l.
portions of 10^ potassium carbonate, worked up as usual, and evaporated.
D istillation of the residue gave 92.3 g. (9^.1^) of a pale yellow oil,
b .p . l 62- l 65°/2 mm., which solidified in the receiver.
Recrystallization from methanol gave colorless prisms (3 crops),
m.p, 68- 69®, in about 90$ yield (lit. m.p. 69- 70®).^
■When the acid chloride of V was prepared with thionyl chloride,
yields of the ketone were about 3^ low er.
1 .2-D ihvdro- 4 -methvlph 9nanthrene (VII)
To 117 ml. ( 0.30 mole) of me thylma gne si urn bromide in e th e r ,% a
solution of 50.0 g. (0.255 mole) of VI in 25 O ml. of anhydrous ether
was added dropwise for a period of 1 hr. The reaction mixture was
refluxed with stirring for an additional hour, cooled, and poured into a
mixture of 100 g. of ice in 100 ml. of 12 N hydrochloric acid. The
layers were separated, and the organic phase together with two benzene
V . E, Bachmann and R, 0 . Edgerton, J . Am. Chem. Soc., 62. 2219 (1940).
2Arapahoe Chemicals Inc., Boulder, Colorado. 30 extracts of the aqueous phase was washed twice with 100-ml. portions of
3 N hydrochloric acid, worked up as usual, and evaporated. The resulting oil was dehydrated by dissolving the material in a solution of 0.50 g. of jg-toluenesulfonic acid in 500 ml. of anhydrous benzene. The resulting
solution was refluxed overnight, the water being removed continuously as the benzene azeotrope via a Dean Stark apparatus. The reaction mixture
was cooled, washed tw ice w ith 100-ml. portions of 10^ potassium carbonate
solution, worked up as usual, and evaporated. The residue was rapidly
distilled to give 45.2 g. (91.3#) of VII, b.p. l45-150°/l.5 mm."'
The carbinol could be isolated by hydrolizing the addition
product with saturated ammonium chloride solution; however, the highest
yields of VII were obtained when the intermediate was not isolated.
4-Methvlphenanthrene (VIII) The distillation apparatus described previously was charged with 300.0 g. (1.55 moles) of freshly distilled VII, and 300 mg. of 10# palladium-charcoal catalyst was added to each portion. The resultant
mixture was heated in a salt bath at 300-320°. After 7 hr., nearly the theoretical quantity of hydrogen had been evolved, and evolution of
additional gas had essentially ceased. After cooling, the catalyst was
removed by filtration and the product was distilled to give 282.0 g.
(94.8#) of VIII, b.p. 148-150°/2.5 mm., m.p. 48-52°. Recrystallization
from ethanol containing a small amount of acetone (< 5#) gave large
colorless prisms, m.p. 50-52°. The yield of pure hydrocarbon was 2?1 g.
(91.2#) (lit. m.p. 49-50°).%
^R. D. Haworth, J, Chem. Soc., 1125 (1932). 2W. E. Bachmann and R. 0 . Edgerton, J . Am. Chem. Soc., 62, 2219 (1940). 31 4-Phenanthroic acid (IX)
A mixture of 235«0 g. (1.22 moles) of VIII, 5^7.0 g. (1.83 moles) o f sodium dichrom ate d ih y d rate, and l400 ml. of water was heated in a rocking bomb at 250® for 28 hr.^ The contents of the cooled bomb were
removed, and the bomb was washed twice with 100-ml. portions of hot 5$
potassium hydroxide solution, then twice with 100-ml. portions of 50 ^ ether-benzene solution. The combined extracts and the original aqueous so lu tio n were f il te r e d , and the green chromium oxide resid u e was washed
alternately with 5'^ potassium hydroxide and with benzene. The organic phase was extracted twice with 100-ml. portions of 5^ potassium hydroxide
solution, and the aqueous phases were combined. The resultant organic
phase was worked up as usual, evaporated and distilled to give 15.4 g.
(6.6^ of 4-methylphenanthrene, b.p. 152-154®/3 mm., as recovered starting
material. The combined aqueous phase was extracted with 300 ml. of benzene and was acidified by pouring into 1000 ml. of 3 N hydrochloric acid. The crude acid was collected by filtration, washed thoroughly with
water, and dried to give 228.0 g. of crude 4-phenanthroic acid (8?.^
based on unrecovered starting material). This material was recrystallized
with difficulty from chloroform-Skelly F to give the pure acid, m.p.
172-173° (lit. m.p. 173. 3- 174. 5 °).^ Subsequent reactions were run utilizing the crude material, without recrystallization.
^L. Friedman, D. L, Fishel, and H. Shechter, J. Org. Chem., 30. 1453 (1965). 2 K. G. Rutherford and M. S. Newman, J. Am, Chem. Soc., 79. 213 (1957). 32
Methyl 4-phenanthroate
To a suspension of 22.2 g. (0.10 mole) of IX in 250 ml. of anhydrous ether was added in portions, with swirling, a freshly prepared solution of approximately 6.6 g. (0.158 mole) of diazomethane in 300 m l. of ether.^ A vigorous reaction, evidenced by evolution of nitrogen, was noticeable during addition of the first 250 ml. After addition was
completed the reaction was allowed to stand at room temperature for 2 h r .; then approximately 100 ml. of ether was slowly distilled. The resultant
so lu tio n was ex tracted with 150 ml. o f a 5 ^ potassium carbonate solution
which upon acidification yielded no starting material. The ethereal
solution of product was worked up as usual and evaporated to give a
yellow o il which upon crystallization from methanol gave 17.0 g. (?2 . 3^)
of methyl 4-phenanthroate, m.p. 83-84° (lit. m.p. 84.8-85.5).^ Chroma
tography of the bulk of residual material on alumina with benzene gave an
additional 5.6 g. (23.7'/®) of solid, m.p. 81-84°. Total yield was 22.6 g.
(96^).
4-Phenanthrvlmethanol (X)
To a solution of 5.70 g. (0.15 mole) of lithium aluminum hydride in 700 ml. of refluxing anhydrous ether was added over the course of 1
hr. a solution of 22.2 g. (0.10 mole) of 4-phenanthroic acid in 800 ml.
of anhydrous benzene. When addition had been completed, the reaction
The solution of diazomethane was prepared from 18 g. of Bis- (N-methyl-N-nitroso)terephthalamide ( 70^ in mineral oil) as described by J . A. Moore and D. E. Reed, Org. S yn., jjl, l 6 (I96I). 2 G. K. Rutherford and M. S. Newman, J. Am. Chem. Soc., 22. 213 (1957). 33 mixture was cooled in an ice bath and hydrolysis of the excess hydride was accomplished ly the slow addition of 10 ml. of water. The organic phase was decanted, and the solid aluminum salts were triturated three times with 500-ml. portions of boiling benzene. The combined organic phase was worked up as usual, and the solution was concentrated to a final volume of about 250 ml. and allowed to crystallize overnight. The resultant solid was removed by filtration to give 16.4 g. (?8.9^) of nearly white needles. Concentration and crystallization of the mother liquors gave an additional 3.7 g. ( 17.8^) of slightly yellow solid.
Recrystallization of the product from benzene gave 19.^ g. (93.6/o) of the product as white needles, m.p. 145-145.5° (lit. m.p. 144-145°)
4-Phenanthraldehvde (XI)
To a rapidly stirred solution of 250 ml. of reagent grade pyridine was added in portions over the course of 1 hr. 25.0 g, (0.25 mole) o f chromium trio x id e . To the re s u lta n t bright-orange suspension of complex was added a solution of 20.8 g. (0,10 mole) of X in 200 ml. of pyridine. The reaction mixture immediately turned black and was allowed to stand with occasional swirling for 1? hr. The resulting mixture was then hydrolyzed by pouring onto 600 ml. o f ic e . The so lid chromium s a lts were removed by filtratio n and thoroughly washed with water and ether- benzene solution. The resulting solution was then continuously extracted with benzene for 48 hr. The resulting organic phase was washed with
200-ml. portions of 1 N hydrochloric aoid until removal of the pyridine
^P. J. C. Fierens, R. H. Martin, and J. Van Rysselberg, Helv. Chim. A cta., ]8 , 2005 (1955). 34 was completed, and then worked up as usual. Evaporation of the solvent gave a nearly black oil which was dissolved in cyclohexane and filtered
to give a yellow solution with the dark material remaining as an insolu
ble tarry mass. Crystallization of the product from the yellow solution
gave 17.2 g, (83. 5^) of 4-phenanthraldehyde, m.p. 83-84°.'*
Dimethyl oC-4-phenanthralmalonate (XII)
A solution of 20.5 g. (O.IO mole) of XI, 15.4 g. (O.II6 mole) of
dimethylmalonate, 2.0 ml. of piperidine, and 1.25 g. of benzoic acid in 300 ml. of thiophene-free benzene was refluxed for 5 hr. The water
formed in the reaction was continuously removed as its benzene azeotrope
with a Dean Stark apparatus. After cooling, the solution was extracted
three times with 250-ml. portions of 3 N hydrochloric acid solution and worked up as u su al. The solvent was removed and the re s u ltin g red-brown oil was crystallized from Skellysolve B to give 23.4 g. (73.8^) of the
product, m.p. 80-81°.
G. K. Rutherford, unpublished research report, Ohio State Univer s ity ( 1956), reports data for this compound as follows; m.p. 85- 86° Analysis for C^fHiQO Calcd; C, 87.4; H, 4.9 Found: C, 87.3; H, 4.9 2 G. K. Rutherford, ibid., reports data for this compound as follow s ; m.p. 80-81° Analysis for C 20H16O4 Calcd.; G, 75.0; H, 5.0 Found; C, 74.8; H, 5.3 The corresponding diacid obtained by saponification, m.p. 231- 232° (d ec.) naut. equ. Calcd.: 292 Found; 293 35 Ethyl oÇ-cyano-^phenanthrylacrylate (XIV)
A solution of 20.5 g* (O.IO mole) of XI, 12.5 g. (O.ll mole) of ethyl cyanoacetate, 2,0 ml. of piperidine, and 1.0 g. of benzoic acid in
250 ml. of thiophene-free benzene was refluxed for 3 hr. The water formed in the reaction was continuously removed as its benzene azeotrope with a Dean Stark apparatus. After cooling, the solution was extracted
three times with 250 ml. of a 3 K hydrochloric acid solution and worked
up as usual. The solvent was evaporated to a volume of about 100 *.il.
Upon cooling pale yellow needles of the condensation adduct crystallized.
Additional product was obtained by the addition of Skellysolve F to the mother liquors. The total yield of XIV thus obtained was 26.7 g. (88.7#), m .p. 132- 133°.^
Isopropylidene malonate
To a stirred suspension of 104.0 g. (1.0 mole) of powdered
malonic acid in 120 ml. (1.2 moles) of acetic anhydride was added slowly
3.0 ml. of concentrated sulfuric acid. The resulting solution was cooled
to a constant temperature of 20- 25 ® while 63.8 g. (1.10 ml.) of acetone
was added slow ly. The re s u ltin g so lu tio n was stoppered and allowed to stand in the refrigerator overnight during which time crystallization
occurred. The resulting crystalline product was removed by suction
filtration and washed three times with 15-ml. portions of ice water.
After allowing the solid to partially dry in the air for 3 hr.
^G. K, Rutherford, ibid., reports data for this compound as follow s ; m.p. 134 - 135 ° Analysis for C2 oHi ^N02 î Calcd.; C, 79.7; H, 5.0; N, 4.6 Found; C, 79.8; H, 4 .9 ; N, 4.5 36 recrystallization was effected by dissolving the solid in 150 ml. of acetone at room temperature, filtration of the solution, and addition of
300 ml. of ice water. Upon allowing the solution to stand overnight in the refrigerator, the product had again crystallized to give 43.0 g. (30.2/5) of white needles, m.p. 91- 92° (lit. m.p. 91.5-92®).^
Isopropylidene 4-nhenanthralmalonate (XIIl)
To a stirred solution of 7.2 g. (O .05 mole) of isopropylidene malonate and 6.6 m l. (O.O 5 mole) of collidine in 50 ml. of dimethyl sulfoxide was added a solution of 10,3 g. (O .05 mole) of 4-phenanthralde- hyde in 25 ml. of dimethyl-sulfoxide. The resulting solution was allowed to s t i r a t room tem perature fo r 20 hr. The re s u lta n t dark red so lu tio n was poured over about 500 g. of ice at which time the product precipitated as a yellow s o lid . The s o lid was re c ry s ta lliz e d from I 50 ml. of methyl alcohol containing 10^ acetone to give 11.3 g. (6?.3,^) of bright yellow crystals of XIII, m.p. 184-18?°. Repeated crystallizations gave the analytical sample, m.p. 189-191° (dec.).
Analysis for C 21H15 O4 ; Calcd.; C, 75.9; H, 4.8 Found: C, 75.8; H, 4.7
Ethyl o To a solution of 20.0 g. (0.66 mole) of ethyl «C-cyano-/3-4- phenanthralacrylate in 400 ml. of anhydrous thiophene-free benzene was added dropwise over the course of 0.5 hour an equimolar amount of ^D. Davidson and S. A. Bernhard, J. Am. Chem. Soc., 20, 3426 (1948). 37 l-naphthylmagnesium bromide in ether-benzene. The reaction complex separated as a heavy red oil. The reaction mixture was allowed to stir at room temperature for 18 hr., after which time the complex had entirely dissolved. The reaction was hydrolyzed by the addition of saturated ammonium chloride solution; the organic layer was separated and worked up as usual. The solution was concentrated to a volume of about 200 ml. and allowed to crystallize to give 12.6 g. of white crystals, m.p. 144-153°. The mother liquors were dissolved in a minimum of benzene and chromatographed through a short column of activated alumina to give 2.6 g. of starting material, and an additional 6.3 g. of product, m.p. 147-158°. Combination and recrystallization of the product from benzene gave 17.4 g. of colorless prisms of XV, m.p. 157-160° (70.7^)^ based on recovered starting material. oC-Cyano- 0 - 1-naphthyl- -4-phenanthryl- prorionic acid (XVI ) A suspension of 4.29 g. (O.Ol mole) of XV in 20 ml. of 15^ potassium hydroxide solution and 50 ml. of methyl alcohol was refluxed for 5 hr. At the end of this time the solution had become essentially homogeneous. After cooling, the reaction mixture was filtered into 300 m l. of 6 N hydrochloric acid solution. The product which precipitated immediately was collected by filtration, and recrystallized from G. K. Rutherford, ibid., reports the following data for this compound ; m .p. 158- 160° Analysis for C 20H22NO2 : Calcd.Î C, 83.9; H, 5.4; N, 3.3 Found; C, 83.7; H, 5.4; N, 3.2 38 benzene-petroleum ether (30-60°) to give 3.8 g. (89.^) of XVI, m.p. 203- 205 ° (dec.).'' (3 -l-Naphthvl-/3-4-phenanthryl- propionio acid (XVII ) To a solution of 5.8 g. (0.10 mole) of potassium hydroxide in 10 ml. of water and 150 ml. of ethylene glycol (commercial) was added 4.29 g. (0.01 mole) of the cyano-ester XV. The resulting solution was heated to reflux while the evolved ammonia was swept by a slow stream of nitrogen into a trap containing 50 ml. of 0.10 N hydrochloric acid (50^ of the theoretical amount) with phenolphthalein added as the indicator. After refluxing about two hours the half-life of the reaction had been exceeded. After 6 hr, of refluxing, 93^ of the evolved ammonia had been accounted for by titration, and further evolution was not noted. The reaction mixture was allowed to cool under nitrogen and was diluted with water to a volume o f I5 OO ml. The aqueous solution was extracted three times with ether to remove the ethylene glycol and the resulting aqueous phase was filtered into 5 OO ml. of cold 6 N hydrochloric acid. The pale tan precipitate was collected by suction filtration, recrystallized from benzene, and dried in a vacuum oven to give 3.43 g. (91.3^) of XVII, m.p. 209- 211.5 ° . Analysis for Calcd.Î C, 86.2; H, 5.3; 0. 8.5 Found: C, 85.6; H, 5*3; 0, 8.6 C, 86.1; H, 5.2; 0, 8.? E. Koohendoerfer, unpublished research notes, Ohio State Univer s ity , i 960, reported m.p. 204-206° (dec.). Analysis for Calcd.: C, 83.8; H, 4.77; N, 3.49 Found: C, 83.9; H, 4.99; N, 3 . ^ 39 Methyl 0 -1-naphthyl- (3-k- phenanthrylpropionate A solution of 2.0 g. (5.32 mmoles) of the acid XVII in 150 ml. of anhydrous benzene was treated with an excess of freshly prepared diazo methane in ether.^ The excess diazomethane was removed by slowly dis tilling 50 ml. of solvent. The resulting solution was evaporated, and the residual oil was crystallized with considerable difficulty from ether to give 3,66 g. (9^^) of methyl j3-1-naphthyl-/3-4-phenanthrylpropionate, m.p. 108-111°. Analysis for ^28^22^2’ Calcd.; C, 86.2; H, 5.6; 0, 8.2 Found: C, 86.4; H, 5*6; 0, 8.0 P -(Aminome thyl)-y -l-naphthyl-T" - 4-phenanthrylpropanol (XVIII )' A solution of 10.0 g. (23.3 mmoles) of the nitrile ester XV in 400 ml, of anhydrous benzene was added slowly to a solution of 2.65 g. (70 mmoles) of lithium aluminum hydride in ether. An additional 400 ml. of ether-benzene was added and the mixture was refluxed with stirring for _ca. 24 hr. After cooling in an ice bath, water was added carefully u n til no re a c tio n was ev id en t (30 m l.). The re s u ltin g m ixture was continuously extracted for 36 hr. The organic portion was dried in the usual fashion and evaporated to give 8.5 g. (93.6^») of a light tan solid, m.p. 158- 170°. This solid was re crystallized from benzene-ether to give 7.9 g. (86. 8^) of XVIII as white needles, m.p, 169.5-171°. Further recrystallizations did not change the melting point. ^ J. A. Moore and D. E. Reed, Org. Syn., 41, I 6 ( I 96I). 40 A nalysis fo r C23H2^N0; Calcd.; G, 85.8; H. 6.3; N, 3.4; 0, 4.5 Found; C, 85.8; H, 6.3; N, 3.4; 0, 4.5 A Van Slyke amino nitrogen determination by Huffman Laboratories, Inc., 3830 High Court, P. 0. Box 350, Wheatridge, Colorado, 80033, showed; Calcd.; 3.58 Found; 3.48 2-(l-Naphthyl-4-phenanthrylmethyl)- 1..3-propanediol (XIXT To a solution of 1.95 g. (5.0 mmoles) of the amino-alcohol XVIII i n 30 ml. of glacial acetic acid was added with vigorous stirring 60 ml. of a saturated aqueous sodium nitrite solution. Immediate gas evolution was noticed and a gummy yellow solid precipitated. The reaction mixture was allowed to stir for an additional 15 min. and was then poured into 600 ml. of ice water. The aqueous suspension was extracted four times w ith 150 -ml. portions of ether-benzene and the combined organic phase was worked up as usual. Evaporation of the solvent gave a yellow glass which could not be crystallized. The above residue was dissolved in 150 ml. of methyl alcohol and 15 ml. of a 3O/S potassium hydroxide so lu tio n was added. The yellow solution immediately turned black. After allowing the reaction mixture to reflux for 30 min. it was poured into 6OO ml. of ice water and the resultant aqueous suspension extracted six times with 150 -ml. portions of ether-benzene. The combined organic phase was worked up as usual and was evaporated to give 1.73 g. of an extremely viscous red-brown oil. The oil was partially crystallized from chloroform-Skellysolve B to give 41 0.64 g. (33.5^) of white needles, m.p. 1 1 0 -1 1 5 ° . A portion of this material recrystallized from the same solvent melted at 1 1 1 -1 1 8 ° . However, if the temperature were allowed to rise slowly, the melt recrystallized at about 1 2 3 ° and remelted at 1 8 4 -1 8 6 ° . By drying the low m elting m aterial in a vacuum oven a t 105° for 24 hr. the higher melting solid was obtained again and used as an analytical sample. Analysis for Calcd.; C, 85.7: H, 6.2; 0, 8.1 Found: 0, 85.7; H, 6.4; 0, 7.9 The n.m.r. spectrum in d^-dimethyl sulfoxide showed the following characteristic peaks. r- M ultipli city No. of Hydrogens Type 5.5 3 2 0-H 6.45 m ultiple 4 methylene 7.55 m u ltip le 1 te r tia r y 3.55 m u ltip le 1 di-benzilic .3=11= Naph methyl)glutaric acid (XX) To a so lu tio n o f 200 g. (0.51 mmole) of the d io l, XIX, in 25 ml. of reagent grade pyridine was added about 1 ml. of methanesulfonyl chloride. After 3 min., white needles of pyridine hydrochloride were noticed. The reaction mixture was allowed to stir for 2.5 hr. at room temperature, and was then poured into 400 ml. of ice water. The white - precipitate which formed was extracted into benzene and the combined organic phase was washed twice with 100-ml. portions of 5/^ potassium hydroxide solution and worked up as usual. The solvent was evaporated k z to give about 320 mg. of a clear glass whose in fra re d spectrum showed no absorption in the 0-H region. This crude product was dissolved in 25 ml. of dimethylformamide and added to a solution of 0.50 g. of potassium cyanide and 0.10 g. of potassium iodide in 15 ml. of water. The resulting solution was heated at about 90° with stirring overnight. The cooled solution was diluted with 600 ml. of water and extracted four times with ether-benzene. The combined organic phase was worked up as usual and was evaporated to give the crude dinitrile as a tan viscous material. A solution of 10 ml. of 15^ potassium hydroxide solution and 50 ml. of commercial ethylene glycol was added to the crude di-nitrile from above and heated at reflux overnight. The solution was cooled, diluted with 800 ml. of water and extracted twice with 100 ml. of ether. (The organic portion upon the usual work up gave only a trace of brown tar.) The aqueous phase was poured slowly into 500 ml. of 3 N hydrochloric acid and 500 ml. of cracked ice. The resulting suspension was extracted four tim es w ith ether-benzene and the combined organic phase was worked up as usual. The solvent was evaporated to give I 63 mg. (?1.^) of a tan solid. This sample was recrystallized from benzene-ethanol to give I 5 I mg. (66$^) of a white solid, m.p. 1 9 1 -2 0 5 °» Three recrystallizations from benzene- ethanol gave an analytical sample, m.p. 199- 206° . Analysis for Calcd.; C, 80.3; H, 5.4; 0, 14.3: N.S., 224 Found; C, 80.5; H, 5.5; 0, 14.0; N.E., 221