THE VERATRINE ALKALOIDS In the previous paper (1)

16 Pages·2003·0.68 MB·English

THE VERATRINE ALKALOIDS
IX. THE NATURE OF THE HYDROCARBONS FROM THE
DEHYDROGENATION OF CEVINE
BY LYMAN C. CRAIG, WALTER A. JACOBS, AND GEORGE I. LAVIN
(From the Laboratories of The Rockefeller Institute for Medical Research,
New York)
(Received for publication, February 1, 1941)
In the previous paper (1) we have reported the isolation of a
series of hydrocarbons from the selenium dehydrogenation of
cevine. Since the amount of each substance isolated in a form
approaching purity was too small for extended investigation by
chemical transformation, our attention has been turned to a study
of their absorption spectra. Considerable information is now at
hand in the literature regarding the types of absorption spectra
in the region of the ultraviolet which are more or less characteristic
of the various aromatic ring systems. The formulations of our
unknown hydrocarbons as well as their general nature have made
them therefore particularly interesting for a study from this
standpoint. The results of these investigations are reported in
this paper.’
The simplest hydrocarbon of the series appeared to possesst he
formula C&H12 derived by analysis of the hydrocarbon itself and
of its picrate. The number of carbon and hydrogen atoms in
this formulation at once places limitations on the possible ring
systems which can be considered. A number of combinations
of a benzene ring attached to unsaturated 5-membered rings such
as indene might be considered but such unsaturated systems could
scarcely be expected to withstand the conditions of dehydrogena-
tion. Only a naphthalene ring system with a saturated ring
attached can be seriously considered. The possibilities in this
1 The absorption curves were obtained with a Spekker spectrophotometer
and a small Hilger quartz spectrograph. The solvent in each case was
absolute alcohol.
277
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278 Veratrine Alkaloids. IX
category are 4,5-benzohydrindene, 5,6-benzohydrindene, peri-
naphthane, and one of the four possible methylacenaphthenes. Peri-
naphthane melts at 60” and gives a picrate melting at 160” (2),
whereas 5,6-benzohydrindene melts at 94” and yields a picrate
melting at 120’ (3). 4,5-Benzohydrindene (4) is an oil and its
picrate melts at 109-110”. Our substance was likewise an oil
but the small amount of substance available because of the very
tedious process involved in its isolation did not permit recrystal-
lization of its picrate to a constant melting point. The melting
point, however, on the final recrystallization changed only from
103-105” to 106-107”. It therefore appeared to approach closely
the properties of 4,5-benzohydrindene (Formula I). Further
dentity now appears to have been definitely established by a
direct comparison with synthetic material which was very kindly
placed at our disposal by Professor J. W. Cook of the University
of Glasgow. A mixed melting point of the picrates from both
sources did not show an appreciable depression and the two
substances appeared identical in all their properties. Comparison
of the ultraviolet absorption spectrum of synthetic 4,5-benzo-
hydrindene with that of our oil (Fig. 1) with a few minor excep-
tions showed a close agreement and gave further strong support
to the question of identity.
The next hydrocarbon of the series isolated appears from the
analysis to possess the formula CX7H16. Empirically this formu-
lation allows for a total of ten double bonds plus rings and cor-
responds to a trimethylphenanthrene or an anthracene. However,
its ultraviolet absorption spectrum curve is quite different from
that of either anthracene or phenanthrene (Fig. 2). The differ-
ence appears to be sufficiently great to eliminate the double bond
arrangement of either of these ring systems from serious
consideration.
The formulation of the next three hydrocarbons, Cn~H18, CMHZ~,
Craig, Jacobs, and Lavin 279
and C24H30 respectively, also implies a total of ten double bonds
plus rings and this fact, along with their common origin, suggests a
close relationship in the ring structure of the four hydrocarbons.
The striking similarity of their absorption spectra as shown in
Fig. 3 makes this seem even more evident.
Although the type of their absorption spectra seems to be un-
related to either the phenanthrene or the anthracene type, it,
appears to approach more closely the general type given by naph
- Btmzohydrjndene
l C,H, hydnocarbon
I
3.2
3.0
2.0
2.6
2.4
2.2
20
22w 24ca 2600 3200 3400
FIG. 1
thalene derivatives. Accordingly, a naphthalene ring system to
which are joined three other rings or double bonds might be con-
sidered as a possibility. Since a cyclopentenonaphthalene ring
system in the hydrocarbon C13H12 has been isolated from the same
dehydrogenation mixture, it could be suggested that these hydro-
carbons contain such a ring system to which either two additional
rings are attached or one ring containing a double bond. Of
these two possibilities the latter might appear to be more definitely
280 Veratrine Alkaloids. IX
suggested by the absorption spectra on the naphthalene basis.
These show a greater absorption coefficient in general than do
naphthalene derivatives which do not carry a group containing a
conjugated double bond.
n in A.
FIG. 2. X = CITHIG hydrocarbon; o = phenanthrene; 0 = anthacene;
q = diphenyl.
It is improbable from general experience that such an extra
unsaturated ring could be s-membered. Should an extra B-mem-
bered ring be attached to the naphthalene ring system in any
positions other than the 1,8 or peri positions, the hydrocarbon
would then be a tetrahydroanthracene or phenanthrene derivative
and under the conditions used for the dehydrogenation from which
it was isolated, such a derivative might be expected to be dehydro-
Craig, Jacobs, and Lavin 281
genated to its parent phenanthrene or anthracene. While or-
dinarily failure to isolate such a derivative from a very complex
mixture cannot be considered as final evidence against its presence
there, it should be pointed out that a very thorough search was
made which had resulted in the isolation of some fifteen substances
among which are five hydrocarbons having almost the identical
properties which such derivatives would possess. Nevertheless,
FIG. 3. A = ClsH12; X = C17H16; 0 = CIeHls; 0 = C19Hzo; 0 = C24H30
all attempts to isolate tetrahydrophenanthrenes or anthracenes
have failed.
This evidence should be considered together with the fact that
there may be present in the alkaloid a hydrogenated naphthalene
ring system which is substituted in the 1,8 positions, if our deduc-
tions (5) regarding the general structure of decevinic acid and
the assumption of its primary character are correct. Thus the
possibility must be considered that the more complex hydrocarbons
may contain the cyclopentenonaphthalene ring system to which a
further ring is joined at the peri positions. In accordance with
282 Veratrine Alkaloids. IX
this, there may be suggested two structures which are derivatives
of the little studied benzonaphthene ring system, Formulas II
and III, and a third structure, Formula IV. In each case a
number of modifications are of course conceivable on the basis of
different arrangements of the double bonds.
H,C-CH, H&&Hz
2
11 III 1V
From the work of Pestemer and Manchen (6) the approximate
effect on the absorption spectrum of a double bond conjugated
with the naphthalene ring system can be seen. The absorption
coefficient is increased considerably and the bands are shifted
toward the longer wave-lengths, an effect in conformity with
past experience for the conjugation of a double bond with an
aromatic nucleus. The opposite of this last effect has been noted
in the case of our substances, if referred to naphthalene.
The question might persist as to whether the reversed shift
noted with our substances could be due to any one if not all of
the possible arrangements of rings and double bonds in the
benzonaphthene ring system.
Since the synthesis of any of the ring structures represented
above is a major research in itself and since hydrocarbons with
this ring structure appear io be little if at all investigated, it
seemed advisable to turn to simpler known substances in order to
see what arrangement of double bonds might be indicated in our
hydrocarbons by the study of the absorption spectra of such model
substances.
Accordingly, the yellow ketone of perinaphthene (benzonaph-
thene) was prepared according to the directions of Fieser (2) and
subjected to dehydrogenation under the same conditions used for
cevine (1). A hydrocarbon could be isolated readily which,
however, did not give the analytical data expected for perinaph-
thene but rather those for a hydrocarbon with 2 more H atoms,
Craig, Jacobs, and Lavin 283
oiz. perinaphthane, produced presumably by disproportionation.
The melting point also agreed with that reported for perinaph-
thane.
Although such behavior seemed in itself to be against the likeli-
hood of the more complex hydrocarbons discussed above with-
standing the dehydrogenating effect of selenium, we have gone
further and synthesized a hydrocarbon with the empirical formula
of methylperinaphthene by the action of methyl magnesium iodide
on perinaphthenone. Although we had expected the initial
formation of an alcohol which could then be reduced and dehy-
drated to methylperinaphthene, a hydrocarbon among other
products resulted which gave the proper analytical figures for the
desired one. The mechanism of its formation is obscure but may
be possibly due to the reducing action of the reagent (7). Aside
from the hydrocarbon a yellow solid was also isolated which
melted at 87-88” and gave analytical figures corresponding to the
empirical formula of C14H100. The exact nature of this product
was not determined.
The hydrocarbon melted at 63-65” and proved to be somewhat
unstable. Although it could be distilled in a high vacuum to
give an almost colorless crystalline solid, upon standing at room
temperature a green color developed in the course of a few hours.
The absorption spectrum in ethyl alcohol is represented by the
curve given in Fig. LI.~ Comparison of this curve with the ab-
sorption spectra curves of simple naphthalene derivatives shows
that in this derivative the conjugated double bond increases the
absorption and also displaces the bands considerably toward the
longer wave-length. This is a result in agreement with the absorp-
tion shown by propenylnaphthalene (6) and therefore cannot very
well account for t,he type of absorption shown in Fig. 3 for the
hydrocarbons from cevine.
We have further subjected the hydrocarbon methylperinaph-
thene to treatment with selenium under the same conditions
used for the preparation of the cevine hydrocarbons in order to
see whether it would withstand such treatment or possibly undergo
2 In a private communication, Dr. Fieser of Harvard University has
kindly sent us the absorption spectrum curve of a methylperinaphthene,
possibly isomeric with our substance. This curve is in good agreement
with that obtained with our substance.
284 Veratrine Alkaloids. IX
a rearrangement of double bonds to the forms most stable under
such conditions. The hydrocarbon isolated in rather poor yield
from the resulting mixture crystallized when placed in a freezing
mixture but was liquid at room temperature. The analytical
data indicated formation of methylperinaphthane by addition of 2
atoms of hydrogen owing to disproportionation and were in
agreement with the result of the dehydrogenation of perinaph-
thenone. While these results are not sufficient to rule out entirely
l Methylpskqhtima
0 Acenaphthylene
x r.-I-.. %..,A-
2&-
2400 2wx) 2wx) 3m
AiaA.
FIG. 4
such general structures as are represented in Formulas II and III,
they do serve to make them seem even less likely than other general
considerations would indicate.
The formulation represented in Formula IV would be that of
an acenaphthylene derivative. Acenaphthene is reported not to
dehydrogenate with selenium to acenaphthylene (8) but, never-
theless, the absorption spectrum of the latter was determined
and is shown in Fig. 4. This curve seems to be sufficiently different
from those of the hydrocarbons from cevine to remove this pos-
sibility from consideration.
Craig, Jacobs, and Lavin 285
Of various other known types of absorption spectra, that of
diphenyl (Fig. 2) seems to offer considerable similarity to that of
our hydrocarbons. The general shape of the curve is approxi-
mately the same as well as the intensity of the absorption. The
curve of any one ofothe hydrocarbons, however, covers a region
approximately 200 A. displaced toward the longer wave-lengths
from that of diphenyl. This is an effect shown by many examples
in the literature to be caused by the substitution of alkyl groups
or saturated rings on an aromatic nucleus. If any of the four
hydrocarbons is a dipheriyl derivative, two further saturated rings
must be present in order to make up the ten necessary double
bonds or rings and thus conform with the established empirical
formulas. Thus two general possibilities remain; viz., a cyclo-
pentenofluorene derivative and the other a cyclopenteno-9, lo-
dihydrophenanthrene derivative. Both would be expected to
give a somewhat modified diphenyl type of absorption curve.
A comparison of the curves of fluorene, 9, lo-dihydrophen-
anthrene, and the C1,Hle hydrocarbon is shown in Fig. 5. The
curves of fluorene and 9, lo-dihydrophenanthrene were replotted
from data taken from the curves of Askew (9).
Before a 9, lo-dihydrophenanthrene derivative can be seriously
considered, the possibility that such a derivative would resist
dehydrogenation to the corresponding phenanthrene would have
to be weighed. That such a possibility cannot be entirely dis-
missed may be derived from the experience of Bergmann and
Weizmann (10) who found that 1,2-dimethyl- ,4,9,10,11,12-
hexahydrophenanthrene as well as its 7-methoxy derivative did not
dehydrogenate readily to the corresponding phenanthrene and
only in poor yield upon long treatment. Oils giving the proper
analytical data for dihydro derivatives were isolated which were
considered by them to be 9, IO-dihydrophenanthrene derivatives.
This question, however, must be explored more carefully at a
future time.
Thus, the possibility must be considered that the hydrocarbons
from the selenium dehydrogenation of cevine could be derivatives
of a cyclopentenophenanthrene and if so, barring obscure rear-
rangements, that cevine could contain such a completely hydro-
genated ring structure. However, the failure to dehydrogenate
to a phenanthrene has not been encountered in the sterols hereto-
fore as far as we are aware.
286 Veratrine Alkaloids. IX
The other possibility, a cyclopentenofluorene derivative, wouId
not be an unlikely product of a selenium dehydrogenation.
In
favor of such a structure can be mentioned the behavior of all
3.2
3.0
2.6
2b
2.4
four of our hydrocarbons when subjected to the Vanscheidt color
test (11). When a small amount of the hydrocarbon is dissolved
in pyridine, a drop of alcoholic KOH added, and the solution
heated with shaking, a yellow color develops which turns gradually