THE VERATRINE ALKALOIDS

XXXIII. THE ISOMERIC FORMS OF CEVINE, GERMINE, AND

PROTOVERINE

BY HERBERT JAFFE AND WALTER A. JACOBS

(From the Laboratories of The Rockefeller Institute /or Medical Research, New York,
New York)

(Received for publication, May 31, 1951)

The highly hydroxylated tertiary veratrine base cevine (l), C27H.,aOsN,

its isomer germine (2), and the companion baseprotoverine (3), C27H4B09N,
have been assumed, from earlier work, to possessone point of unsatura-
tion. Although t,his was not directly demonstrated by hydrogenation
with platinum oxide (except with cevine and nickel), on reduction with
sodium in butanol apparent dihydro bases were obtained. On the other
hand, the isomeric substances isogermine and isoprotoverine were readily
hydrogenated to what, were also assumedto be dihydro bases. From t.he
failure to prepare an oxime from cevine (1) by the usual procedure with
hydroxylamine hydrochloride and sodium acetate and because of the un-
eventful character of its ultraviolet absorption spectrum, t,he presence of a
carbonyl group as such appeared excluded. However, an enoliaed carbonyl
was considered t.o explain the formation from the quaternary salt cevine
methiodide wit.h alkali of an apparent internal salt C&H4508N, which from
pH measurements was found to be completely dissociated like an am-
monium base when half neutralized with HCl. The number of hydroxyl
groups report,ed with each of the natural bases was indicated by the
Tschugaeff-Zerewitinoff determinations, although this procedure is of
doubtful value in distinguishing between one more or less of such groups
when so many are involved. And the later provisional suggestion (4),
based on the use of Barton’s method of molecular rotation differences,
that these bases may be A8(14) -stenols and the iso bases their Al4 isomers
may require reinterpretation.
In a recent report of their studies of the infra-red absorption spectra of
various alkaloids Marion, Ramsay, and Jones (5) have presented evidence
of the presenceof a carbonyl group as such in “cevine,” although no other
data characterizing the substance used by them were given. In view of
this divergence from our early experience and of other data which had
been accumulating, we returned to a study of the nature of the unsatura-
tion in these basesand have obtained preliminary results which present a
more complicated picture than was originally suspected.
A repetition of the examination of the ultraviolet spectrum of the al-
325

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326 VERATRINE ALKALOIDS. XXX111

kaloid now called a-cevine, which was crystallized from dilute ethanol,
has shown again essentially uneventful absorption (Fig. 1) with minor
fractional increase in the usual carbonyl region when taken in ethanol or
chloroform. There was little change after several days’ standing. It was
then found that under the influence of alkali isomerization occurs, which
could be readily followed with the spectrophotometer. A solution of
cy-cevine (about 1 per cent) in ethanol which contained 1 per cent of NaOH
showed a gradual progressive change, and, after a day or so, a marked
absorption in the ultraviolet had developed with a maximum at about
315 to 320 rnM. As presented in the experimental part, extraction with
2.c

Log &
1.0

-+\
+-+\+
‘+
‘+
I I I I 1 ,.+\
2400 2600 2800 3000 3200 3400 3160
0

FIG. 1. 0, a-cevine in ethanol; 0, the same after 47 hours; -I-, cr-cevine in chlo-
roform.

chloroform yielded an amorphous isomerized base, /3-cevine([a], = - W),

which was not crystallized as such. Its ultraviolet absorption is given
in Fig. 2 which shows a maximum about 275 mp. When recrystallization
was attempted from dilute ethanol, more than half gradually separated as
crystalline cr-cevine which now showed only fractional (about 10 per cent)
absorption as presented in Fig. 2, obviously due to contamination with
some p-cevine. The material recovered from the mother liquor also
showed diminished rather than enhanced absorption. Similarly, when the
0, form was treated in solut,ion with a slight excess of HCl, its absorpt,ion
was little affected, even after 24 hours. However, when ether was added,
a major fraction of crystalline hydrochloride was obtained which showed
little characteristic absorption, owing to its apparent reconversion to the
cr-cevine salt (Fig. 2).
As with cr-cevine, t,he p-form did not yield an oxime in the usual manner
 H. JAFFE AND W. A. JACOBS 327

with hydroxylamine hydrochloride and sodium acetate. However, in al-

kaline solution an oxime, although not crystalline, was readily obtained
from each isomer. This derivative, in accordance with the following, is
probably isocevine oxime.
Analogous results have been obtained with a-germ&e ([aIn = +S’).
Its ultraviolet, absorption curve is shown in Fig. 3. The minor fractional
maximum at about 275 rnp is attributable to some contamination with
the following P-germ&e. When Lu-germine was treated with alkali, the
substance recovered could be crystallized from methanol and was still an

I I I I I I I
2400 2600 ‘2800 3000 3200 3400 3 10
A 6)
FIG. 2. 0, @-cevine; 0, same after crystallization; f, HCl salt; all in ethanol

apparent mixture of the 01and @ forms. The relative amounts indicated

by the absorption spectra varied considerably and were probably due to a
variation in the conditions of the crystallization rather than in those of
alkali isomerization or of the extraction. In one case the isolated crystal-
line fraction ([cx]~’ = +S’) yielded the absorption curve shown in Fig. 3.
In other cases only fractional retention of the /3 form was observed. In
an effort to trace the cause of this variation, different conditions were
used and the result appeared to depend upon the chance cryst,allization
tendency from individual solvents and the ready equilibrium shift between
the two forms. When /3-germine, or material rich in it, was allowed to
crystallize from a sufficient volume of chloroform, the major portion sepa-
rated with the solvent of crystallization and showed practically uncvent-
ful absorption.
328 VERATRINE ALKALOIDS. xxx111

cr-Germine was recovered unchanged in attempts to prepare an oxime

in the usual manner. However, with NaOH a rapid separation of a crys-
talline sodium complex occurred from which a crystalline oxime was readily
obtained, identical with the oxime later described.
Protoverine has been given but preliminary study. Its absorption
curve, presented in Fig. 4, shows but fractional absorption in the car-
bony1 region and is consistent with the results from cevine and germine.
Later studies will doubtless yield material, a-protoverine, which should
show minimum absorption in this region and also its conversion to a p form.
The question as to which of the forms of these bases is present in the

FIG. 3. +, a-germine; 0, p-germine; 0, isogermine; all in ethanol

original, naturally occurring esters has been given a partial answer in the
results obtained with protoveratrine. Its ultraviolet absorption curve
presented in Fig. 4 shows but minor fractional absorption in the carbonyl
region. It is possible that the natural alkaloids are esters of the non-ab-
sorbing (Y forms. However, this question will require further study.
It was of interest to determine the relationship of the levorotating iso-
germine to cr- and ,i3-germine. The absorption curve presentBed in Fig. 3
indicates carbonyl absorption. As anticipated, it readily yielded iso-
germ&e oxime without the intervention of alkali. It is apparent that the
conversion of germine to isogermine by the more severe treatment with
alkali (2) is accompanied by additional structural change which creates a
more stable carbonyl group. Of particular interest was the discovery of
the apparent identity of the oximes obtained from cr-germine (with alkali)
 H. JAFFE AlUD 11’. A. JACOBS 329

and from isogermine. As discussed later, the presence of a carbonyl group

in isogermine and the identity of the oximes were substantiated by the
i&a-red spectra. Isoprotoverine, which is also more strongly levorota-
t.ory than protoverine, belongs in a similar category. It likewise exhibits
(Fig. 4) carbonyl absorption and readily yields isoprotowrine oxime.
Our earlier efforts to hydrogenate cevine with platinum oxide catalyst
were made in acetic acid or dilut’e HCl. More recently, however, both
OL- and p-cevine in methanol have been gradually hydrogenated and an
apparently idemical dihydrocevine ([cx]~ = - 15”) was isolated in each
case. Aside from a difference in rotation ([(Y], = -8”), the product bore

2400 2600 2600 3COO 3200 3400 3

FIG. 4. l , protoverine; 0, protoverntrine; +, isoprotoverine; all in ethanol

a strong resemblance to that, previously obtained with nickel catalyst.

The reduction product previously described ([a], = -27”), obtained
wit,h sodium and butanol, is apparently a stereoisomer. Neither isomer
yielded an oxime. Both hydrogenation and reduction with sodium must
eliminate the double bond needed with a hydroxyl for the potential car-
bony1 function.
The nature of the (Y and /3 isomerism and that of the iso basesnow re-
main to be explained. Recent molecular weight determinations of both
cevines taken in camphor were in essential agreement with a monomo-
lecular formula. Earlier degradation studies yielded a number of pyridine
and piperidine bases containing oxygen, which is therefore present in the
steroid side chain, and it now appears possible t.hat one or more hydroxyl
groups could participate with the doubfe bond in the isomerism. The
330 VERATRINE ALKALOIDS. xxx111

possibility that a reversible double bond shift occurs in the neighborhood

of the nitrogen atom which permits formation of an internal quaternary
twitter ion involving a neighboring hydroxyl group was not directly sub-
stantiated by pH measurements made with both QI- and fl-cevine? In
solutions half neutralized with HCl the pK’ of a-cevine at 27” was found
to be 9.67 and that of p-cevine 9.55 at 26.5’, which would be expected
rather of tertiary bases.
The failure to produce an oxime except on the alkaline side appears to
be against the presence of a carbonyl group as such or to be expected of
uninhibited keto-enol isomerism. There is also objection to the possibility

Wavelength B

Frequency cm:’

FIG. 5. Infra-red absorption spectra of the cevines (Nujol mull)

of a potential CO group on carbon 21 or 27, protected in lactol form, with

an OH on carbon 23 or 24, since it is doubtful that such a lactol would
open under alkaline conditions to permit formation through transient
enolization of a more stable trans aldehydic group.
However, further insight into the structures involved has been furnished
by the following correlated infra-red studies. The data are presented in
Figs. 5 and 6. Contrary to the distinctive behavior shown in the ultra-
violet spectrum, the a and fl forms of germine and cevine yield in each
caseidentical spectra in the infra-red from 2 to 14.5 I.C. Surprising as this
result may appear, the ultraviolet and infra-red data are not necessarily
irreconcilable. One may recall that absorption in the infra-red depends
on the presence of a molecular dipole moment, and that, if a structural
1 We wish to thank Dr. L. C. Craig for these data.
 H. JAFFE AND W. A. JACOBS 331

change is effected where the new or modified molecular vibrations are not
attended by a change in this dipole moment, they will not be observed
in the infra-red, although they may well appear as new bands in the ultra-
violet or Raman spectra. For this condition to obtain, the structural
alteration must involve a symmetric& oscillator either formed de novo or
else capable of undergoing modification without loss of symmetry. Ac-
cordingly, the structural difference between the (Y and /3 isomers is prob-
1
P, I 14 13 12 11 10 9 8 7 6 5 4 3

ii1 Wavelength p

40- Iso-Germine

i
1M 1
_“”
80-
90
I

700 750
FIG.
800 850 900
6. Infra-red
Frequency cmY1
1000 110012001300 1500 2000 2500 3000 4000 ’
absorption spectra of the germines (Nujol mull)
1
ably concerned with an i&a-red inactive symmetrical atomic grouping
which can be of the general form shown in Fig. 8.
Moreover, the broad weak band at 1635 cm.-’ (6.13 II) found for the
cevine and germine pairs is characteristic of an ethylenic rather than a
carbonyl absorption.2 On the other hand, a definite carbonyl band is
apparent in the isogermine spectrum at 1700 cm.-’ (5.88 cl). Since only a
potential ketonic function seemsto develop in the change from the a! to
the fl base, the distinction between these must lie solely in the location of
a double bond sufficiently close to a hydroxyl group which can become
enolic. Such a grouping must also conform to the symmetry required
* These results do not agree with data reported by Marion, Ramsay, and Jones
(5) for cevine.
332 VERATRINE ALKALOIDS. XXX111

for its infra-red inactivity. These conditions are to be found in the ac-
centuated group arrangement shown in Fig. 9. Such a grouping is re-
stricted to specific locations in the structure of the tertiary steroid bases.
Among a number of possibilities, the one which seems most satisfactory
involves the terminal ring of the ‘side chain. Assuming the hydroxyl
group to be at position 24, the partial structures shown in Fig. 9 for the
a! and @isomers appear to be in accord with the experimental data.
Furthermore, the apparent identity of the oximes derived from ,& and
isogermines, indicated not only by melting point and rotation but also
by the infra-red spectra obtained with each (Fig. 7), suggests that these

700 750 800 850 900 looo 1100 12001300 1500 2000
FIG. 7. Infra-red absorption spectra of the oximes (Nujol mull)

two isomers must bear a simple tautomeric relationship to each other.

Accordingly, the partial structure of isogermine would be as represented
in Fig. 9. It is evident from these considerations that two distinct iso-
merization processesare involved: (1) a labile allylic rearrangement ac-
counting for the a! ++ p transformation, and (2) an enol-keto tautomerism
accounting for the /3 cf iso isomerization, which is hindered somehow to
favor the enolic fl form. The structures and interrelationships shown in
Fig. 9 summarize the experimental findings, but, of course, it, remains to
be proved that the essential grouping shown is actually located in the
ring system of these compounds as portrayed.
The internal salt G8Hd508N from cevine methiodide, previously dis-
cussed, would find an explanation in the structure shown in Fig. 9, in
which the hydrogen atom attached to the nitrogen is replaced by a methyl
 H. JAFFE AND Vv’. A. JACOBS 333

group. Such a zwitter ionic structure should be sufficiently stable to exist

as such.
Finally, the potassium derivative of cevine, for which Hess and Mohr
(6) suggested a double salt of the formula C27H420sNK.KOC2Hs, could
find its explanation in the parenthet.ical K+ addition shown in Fig. 9 along
with KOC2HS.

EXPERIMENTAL

@-Cevine-A solution of 1 gm. of a-cevine in 100 cc. of absolute ethanol

was treated with 2 cc. of 50 per cent NaOH with thorough mixing. After

Y
2A Af

A
+
FIG. 8. Planar symmetrical atomic grouping: infra-red inactive mode of vibration

(a: -Isomer)
L ((5isomer) J (Iso-isomer)
FIQ. 9. Presumptive structural interrelationships between the isomers and their
derivative forms.

3 days at 25” the solution, which had developed a yellow color, showed
absorption in the ultraviolet with maximum about 320 rnp (log E2.33).
After dilution with an equal. volume of H20 and saturation with COZ,
most of the alcohol was removed in vucuo. Since attempts to induce
crystallization of the clear solution failed, it was extracted twelve times
with chloroform. The dried extract on concentration in vacua yielded a
colorless resin of /3-cevine which was powdered and dried in a desiccator.
It showed no tendency to crystallize promptly from dilute ethanol or
methanol. The ethanol solution was carefully diluted to turbidity and
on standing gradually deposited a small fraction which was largely resinous
with a very minor amount of interspersed crystals. St,anding for several
days of the diluted clear solution was required for crystallization.
The desiccator-dried non-crystalline base showed [cx]~* = - 18” (c =
1.00 in 95 per cent ethanol).
334 VERATRINE ALKALOIDS. XXX111

For the analysis and molecular weight determination it was dried at

110” and 0.2 mm.
CITHIIOIN. Calculated, C 63.61, H 8.51; found, C 63.60, H 8.26

Its ultraviolet and infra-red absorption spectra are shown in Figs. 2 and
5, respect.ively. 0.402 mg. of substance; 4.078 mg. of camphor; A = 7.0”;
mol. wt. found 507, calculated 509.35.
The determination of the molecular weight of ac-cevine dried at 110’
and 0.2 mm. was found less satisfactory because of a deeper color of the
mixture. 0.465 mg. of substance; 4.715 mg. of camphor; A = 6.5”; mol.
wt.. found 546.
A solution of 0.2 gm. of the resin in a small volume of 95 per cent eth-
anol was carefully diluted to incipient turbidity. On long standing char-
acteristic micro platelets gradually separated. In this fraction 0.103 gm.
was obtained which melted at 169-172” after preliminary sintering above
150°.
[cx]: = -19.6” (c = 1.07 in 95% ethanol)

For analysis it was dried at 110” and 0.2 mm.

Found, C 63.59, H 8.56

Its ultraviolet absorption curve, given in Fig. 2, shows but a fraction

of the absorpt,ion of the original amorphous material.
,4 solution of 0.12 gm. of the B form in methanol was treated with a
slight excess of HCl. Addit.ion of ether caused gradual separation of
woolly masses of delicate micro needles; 81 mg. were directly collected
which melted at 244-247”.
For analysis it was dried at 110” and 0.2 mm.
CSTH,,O~NCI. Calculated, C 59.36, H 8.12; found, C 59.52, H 8.02

This substance contained no methoxyl. The ultraviolet absorption is

shown in Fig. 2.
,4 solution of 0.1 gm. of /3-cevine in 95 per cent, ethanol was heated for
5 hours with 0.1 cc. of 50 per cent NaOH and 30 mg. of hydroxylamine
hydrochloride. Aft,er removal of alcohol in vacua the aqueous solution
was continuously extracted with chloroform for several hours. The sub-
stance obtained could not be crystallized but formed a gelatinous deposit
on addition of benzene to t,he ethanol solution with subsequent concentra-
tion. The dried collected substance weighed 65 mg.
CWH,,OIN~. Calculated. C 61.79, H 8.46, N 5.34
Found. “ 60.98, “ 7.99, “-5.47

In similar manner cr-cevine yielded an amorphous oxime which could

not be crystallized. A portion of this material treated in 95 per cent
 I?. JAFFE AND W. A. JACOBS 335

ethanol with a slight excess of HCl followed by careful addition of ether

yielded an amorphous hydrochloride.
Cz~H,,OaNe.IICl. Calculated, N 5.00, Cl 6.32; found, S 4.97, Cl 6.67
The following conditions did not yield the oxime with cr- or P-cevine.
A solution of 0.1 gm. of Ly-cevine, 20 mg. of hydroxylamine hydrochlo-
ride, and 0.1 gm. of sodium acetate in 95 per cent ethanol was refluxed for
18.5 hours. After partial concentration, careful dilution, and addition of
excess ammonia, cevine very gradually crystallized as stout prisms. In
this fraction 61 mg. were recovered which melted at 167-171” after pre-
liminary sintering.
CJIISO~N. Calculated, C 63.61, H 8.51; found, C 63.52, H 8.36
Hydrogenation of Isomeric Cevines-A solution of 0.1 gm. of cr-cevine in
95 per cent ethanol with 50 mg. of platinum oxide, following initial re-
duction of the catalyst, gradually absorbed hydrogen at atmospheric tem-
perature and pressure. After 23 hours this approximated 1 mole. After
concentration of the filtrate the residue crystallized from a small volume
of chilled methanol as micro prisms or pointed platelets which, when col-
lected in the cold, amounted to 48 mg. Under the microscope the major
portion melted at 223-227” and the remainder persisted to 255-260”.
[cl]: = -15.3” (c = 0.62 in methanol for dried substance)

For analysis it was dried at 100” and 0.2 mm.

ClrHtsOaN. Calculated, C 63.36, H 8.87; found, C 63.12, H 8.71

This substance separates from a concentrated chloroform solution as

delicate needles which contain solvent.
When 0.1 gm. of /?-cevine was similarly hydrogenated, the first fraction
from methanol weighed 28 mg. and was indistinguishable from the sub-
stance above. It also showed two melting points. Most of the substance
melted at 226-228” and the remainder at 256-261”. Concentration of the
mother liquor yielded a residue which crystallized from 1 cc. of chloroform.
39 mg. of delicate needles were obtained which contained solvent. This
fraction on crystallization from methanol yielded material indistinguish-
able from the first fraction in form and melting point.
((~1: = -14.8” (c = 0.88 in methanol for dried substance)
Found. C 63.28, H 8.75

/3-Germine--h solution of 0.5 gm. of cr-germine in 50 cc. of absolute

ethanol was treated with 1 cc. of 50 per cent NaOH. After 18 hours at
about 25” the yellow solution showed strong ultraviolet absorption, with
330 VERATHINE ALKiLOIDS. xxx111

a maximum about 315 to 320 mp. After another 2-1 hours the solution
was diluted with an equal volume of Hz0 and partly concentrated in vucuo.
Ry continuous extraction with chloroform for 2 hours, 0.285 gm. of residue
was obtained. Subsequent extraction for 2 hours yielded only 40 mg.
The first fraction, when dissolved in a few cc. of methanol, suddenly crys-
tallized as a mass of micro prisms or four-sided platelets. 0.16 gm. was
collected with methanol and contained about 2 moles of methanol. It
melted at’ 169-171.5”. On the solvent-containing basis
[a]:: = i-6” (c = 0.99 in 95% et,hanol)

For analysis, the substance was dried at 110” and 0.2 mm.
Ca~H~30&.2CH,011. Calculated, CH,OH 11.17; found, 11.46
CarHllOsN. Calculated, C 63.61, H 8.51; found, C 63.67, H 8.40

The ultraviolet and infra-red absorption curves obtained with this sub-
stance are shown in Figs. 3 and 6, together with that of its precursor,
a-germine.
A solution of 0.1 gm. of a-germine in 95 per cent ethanol was refluxed
for 18.5 hours with 20 mg. of hydroxylamine hydrochloride and 0.1 gm.
of sodium acetate. After concentration, dilution, and alkalization, the
mixture was ext,racted with chloroform. On crystallization from methanol
73 mg. of cr-germine were recovered. The major portion melted at 168-
173” and partly cryst,allized on further treating and then melted from
218-227”.
C&IH~~O&. Calculated, N 2.75; found, S 2.94
When the above sodium acetate was replaced with 0.1 cc. of 50 per cent
XaOH, only a few minutes heating on the bath caused sudden separation
of a mass of delicate needles of the T\Ta compound of the oxime. After
30 minutes this was collected and weighed 75 mg. Its solution in water
on continuous extraction with chloroform yielded 70 mg. of material which
crystallized from hot dilute ethanol as spatulated or boat,-shaped micro
leaflets. The oxime melted at 256-261.5”.
[a]: = +16.4” (c = 0.55 in 95y0 ethanol)
CarHllOsNZ. Calculated. C 61.79, H 3.46, N 5.34
Found. “ 61.96, “ 8.13, ‘I 5.22

Isogermine Oxime-A solution of 0.1 gm. of isogermine in 95 per cent

ethanol was heated for 7 hours with hydroxylamine hydrochloride and
sodium acetate. The mixture was concentrated and then diluted with
water; on continuous extraction with chloroform it yielded the oxime
which crystallized from methanol or ethanol as micro prisms or needles
 H. JAFFE .4ND IV. -4. JACOBS 337

melting at 253-261.5”. When mixed with the oxime from fl-germine, the
melting point was 257-259”.
[a]‘, = +18.12” (c = 0.55 in 95% ethanol)

For analysis it was dried at 110” and 0.2 mm.

C2rH1408N2. Calculated. C 61.79, H 8.46, N 5.34
Found. “ 61.64, “ 8.50, ‘I 5.04

Isoprotoverine Oxime-The procedure was that used with isogermine.

The oxime separated from warm dilute ethanol as micro needles which
melted at 237-240” after preliminary sintering.
For analysis it was dried at 110” and 0.2 mm.
C~rH~lOoN~. Calculated. C 59.96, H 8.21, N 5.18
Found. “ 60.28, ‘I 8.06, “ 5.04

Infra-Red Spectra-For this purpose the substances were prepared as

Nujol mulls, and their spectra determined from 2 to 14.5 cc without com-
pensation on a Perkin-Elmer model 21 double beam spectrometer, with
sodium chloride optics, set at resolution 6, response 2, gain 8, suppression
1, and a scanning speed of 0.25 p per minute on a chart scale of 2 inches
for 1 p. Comparative solution spectra in chloroform were precluded ow-
ing to the disparate solubilities and degree of solvation of these substances
in this solvent. The results are shown in Figs. 5 to 7.

All analytical data have been obtained by Mr. D. Rigakos of this labora-
tory.
SUMMARY

The highly hydroxylated tertiary steroid bases cevine, germine, and

protoverine have been shown to be subject to isomerization under the
influence of alkali, a fact responsible for the existence of three interrelated
isomeric forms. It has been inferred that a triad carbon structure, which
bears a secondary hydroxyl group and a double bond, is incorporated
in the ring system, and is involved in this isomerization. As interpreted
from the chemical and spectroscopic data, these isomers are individually
the allylic alcohol, the enol, and the ketone derivatives.
A suggestion for its location in the structure is given.
BIBLIOGRAPHY

1. Jacobs, W. A., and Craig, L. C., J. Biol. Chem., 126, 625 (1938).
2. Craig, L. C., and Jacobs, W. A., J. Biol. Chem., 149, 451 (1943).
3. Jacobs, W. A., and Craig, L. C., J. Biol. Chem., 149. 271 (1943).
4. Jacobs, W. A., and Sato, Y., J. Biol. Chem., 176, 57 (1948).
5. Marion, L., Ramsay, D. A., and Jones, R. N., J. Am. Chem. SOL, 73, 305 (1951).
6. Hess, K., and Mohr, H., Ber. them. Gee., 62, 1984 (1919).