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I. THE CATALYTIC [email protected]@NOF CARONE.
Sabramania Narayana tyer and John Lionel Simonsen.
Darab Dinsha Kanga, Pancbandana Ramaswslmi Ayyar and John Lionel
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Unfortunately, this was found not to be the case. Under the
conditions described in the experimental section, after the absorption
of r mol. of hydrogen, the prodllct consisted mainly of $-menthan-2-one
i ~ ~ i x ewith
unchanged carone and other schstances ; on complete
reduction ( 2 mols. of hydrogen), p-menthane (in sniall quantity),
p-menthan-2-01 (1'4, and 1-p-menthane-2 : %din1 mere obtained.
The p-menthan-2-01 (ii') obtnined was optical!): illactive ancl
differed in one partici,iau only fi-orn the racemi; aicohol described
by Wailach jAmzrrZtw, 1893, 277, 132)-the phenyluretiiane melted
at 1 0 7 ~and not at 75-76?
This discrep;.ncy is in ail probability
due to the fact that the two alcohols are stereoisomeric, since four
raceinic forms are possible.
T h e iormation of l-fi-inenthane-. : 8-diol d u r i ~ gthe hydrogenation
is of some i n t e ~ e s tand it would appear to have been formed by the
hydration of the cycCopropane ring by the very dilute hydrochloi-ic zcid
present in the reaction mixture, the liydroxy.ketonc subsequently
undergoing reduction.
it is somewhat reinarkable thal no evidence was vbtaincd of the
presence oi m-cymrne deri,vativcs, nor does there appear to be any
tendency for cycZoheptane derivatives to be formed. Althougb these
experiments hare riot proceeded in the desired direction, they are
not without interest since they show quite clearly the great tendency
of carone to behave like an ap-unsaturated ketone.
I t is proposed to
investigate other reactions with carone in order to determine how
far this property is general.
T h e carone required for these experiments mas most conveniently
prepared in quantity by the method of Kondakov and Gorbanov
(y. pr. Chein., 1897, 56, 256)
It had b. p. 150-153"/mo innx.,
0.9468, ?g 1.4739, and [a]j,O.- 250%
The most satisfactory method of hydrogenation is the following :
The ketone (10 g.) was dissolved in acetic acid (20 c.c.), platinic
chloride solution (Pt. 10 per cent. ; 5 c.c.) and gum arabic solution
(gum arabic, 2 per cent. ; 2 0 c.c.) were added, ancl the bottle contain1% the mixture was evacuated and filled with hydrogen. A solution 01
colloidal palladium ( I c.c.) was added, the apparatus ag-ain evacuated,
and filled with hydrogen at a pressure of 2 atmospheres. T h e
mixture was mechanically shaken ; hydrogen was rapidly absorbed
during 2-2: hours until approximately 2 litres ( 2 mols.) had been
taken up. T h e mixtures from a number of such experiments were
combined and, after separation of the platinum, the oil was taken up
with ether, the ctbcr washed with sodium carbonate so!uiion until
free from acetic acid, dried, and evaporated. T h e rcsidul cii partly
crystallised on keeping. T h e solid (A) was collected, and the filtrate
c?istiIled under diminished pressure (109 mm.) ; three main fractions
were then obtained, (i) 105-:15", (3)- 135-I~o", (iii) 140-180". T h e
small residue crystailised and was added to (A).
(i) was repeatedly distilied over sodium ;
it then had b. p. i68-169'/685 mm., rlz 0.7984, ng 1.435, was
optically inactive, had a smell resembling that of Eight petroleum a i d
was not attacked by \rTarn1alkaline permanganate (Found : C, 86.0 ;
H, ,i3.9. Calc. : C, 85.7 ; H9 r4.j per cent.). The small quantity
available did not permit the preparation of crystalline derivatives, but
there would appear to be no doubt that the substance is p-menthane.
p-lWeenfha~z-2-oZ.-The higher fractions we>-ekept for some days
in the ice-box and after removal of the solid deposited (this was added
to A), the filtrate was heated with alcoholic potassium hydroxide to
hydrolyse any acetyl derivative present. T h c cyclic alcohol was
distilled in steam and then under. diminished pressure ; b. p. 143-144"!
IOG mnl., d$: oogooq, n3,0'1.457;. It was optically inactive (Found:
C, 76.9 ; H , 12.6. Calc. : C: 70 9 ; H, 12.8 per cent.). The PAezzyLzwrLh/liane crystallised from light petroleum in needles, m. p. 107-roP
(Found : N, 5.4 Calc. : N, 5.1 per cent.)
T h e alcohol (10 g.) was oxidised in acetic acid solution with a
slight excess of chronlic acid; the p-menthan-2-one obtained, b, p.
146-148"/1oo mm., was identified by mcans of the oxime, m. p. 135',
and the semicarbazone, n3. p. 194-195"~ which were compared with
authentic specimens.
O n oxidation with alkaline permanganate :he ketone gave
p-isopropyla$ipic acid, which was purified through the calcium salt
and recrystallised from water, from which it tended to separate as
an oil. T h e acid was very dificult to purify and melted at 78-So"
(Found for the silver salt: Ag, 54.1. Calc. : Ag, 53'7 pel- cent.)
Previous workers (Wallach and ICoehier, A?z~za&%1905, 339, I 13 ;
Wallach, &a?., 1906, 343, 33; 1917, 414, 287) also have found the acid
difficult to crystallise.
solid ( A ) crystailised from ethyl
I-p-Mcnthaze-n : $-&&-The
acetate in large, glistening prisms, m. p. i55-156~~[a!g-4oQ in
chloroform (Found : C, 69.7 ; H, I 1.4. Calc. : C,09.8 ; h,I 1'6 per
It was identified with Z-0-menlhane-i? : 8-diol (Wallach,
AnmaZen, 1917, 4.14, 195) ( I ) by treating it with an acetic acid solution
of hydrogen bromide for some days ; the solid obtained on addition
of water crystal!ised from methyl alcohol in plates, m, p. 57-5P, and
was shown by direct comparison to be terpinene dihydrobromide,
(2) by oxidising it in acetic acid with a slight excess of chromic acid ;
p-menthan-8-01-2-ooe was obtained, and identified by means of the
semicarbazone, rn. p. 149" (Found: N , 18.6. Calc. : N, 18.5 per
De$arimed o f Organic Chew~i~try,
fndian Institute o f Science,
T h e alkaloid conessine has been obtained from the bark and
seeds of Nolarrhena antidysentwica and from the bark of H. c$rica+za
and N~ co~zgobnsis. I t bas formed the subject of a considerable
number of c ~ m r n u n i c a t i o n s , ~but little is known regarding its
chemistry beyond the fact that it has the empirical formula C,,H,,N,
and contains two tertiary -NMe groups.
W e had pianned an extended investigation on this alkaloid,
since, in addition to the intrinsic value attaching to the determination
of its constitution, there was the added interest that there is a
considerable body of clinical evidence indicating that the bark of
I(. a~ztidysentevica is of value in the treatment of diseases of the
dysenteric type (compare Henry and Drown, Trapis. Roy. Sac. Trap.
Med. H y g ~ $1922-4, 17, 61, 381). Unfortunately our experiments had
to be terminated at an early stage, as certain derivatives cf conessine
had an extremely toxic effect on one of us (J. E. S.), giving rise to a
severe attack of giant urticaria. W e prepared a few new derivatives
of conessine, and record the results of our work in the hope that they
may be of assistance to other investigators.
Giemsa and Halberkann observed ( h c . ci~!.,p. 2 1 2 ) that when the
ammonium base formed by treating- an aqueous solntion of conessine
dimethiodide with silver cxide was heated a t 200" under diminished
pressure, trimethylamine was evolved, leaving a crystalline base.
W e have examined this reaction in some detail and have found the
residue to consist of a mixture of at least two bases. One of these,
for which the name apoconessine is proposed, has the formula C,,I-B,N,
having been formed by the elimination of trimeth~lamine,water and
methyl alcohol from conessinedimethyl-ammonium hydroxide. I t
was characterised by the preparation of the crystaIline h y d q e ~ z
Reprinted from the Journal of Ihe Chemirol Society 1926, 2123.
The Followi,viag mould appear to be a complete lis<of the references to conessme in the
Med. Soc. Gombay 1858 4 28 as nereine) - Stenhouse iP*arm. J.
literature : Haines (T-5.
1864 5 493) H ~ n e s(;bid. l w , 6, 432) ; 6Julfs..d& (kotl.,iVaTorhr.:1878, N o . 3 ) ; ~ e i d e l :
~ i s s ! e ) ~G&&,
I858 is$'hysialagische Wirkung des C o n w m e ') ; Dctt (CalcuttaC1:ernical
Examiner's Report 1 8 ~ 0.) Warnecke (Ber. 18SG 19 60) . Paistort? ard Schimer Wid.,
P- 78) ; Polstorff (zkd.,'p. i w ) ; mouael
?hem.: 1887, 16, 391) ; Warnecke (Azf6,
P/raY?n., 1888, 226 718, 281):; Ulrici (%bid.,1818, 256. 57) : Gicmsa a:~d Halberkann ( a k d . ,
P 201) ; Pyman (i,-1919, 115, 163).
sul#har'e and picvate. T h e crystalline nzzfhodide was reconverted into
the original base on treatment with silver oxide.
W e have also made some preliminary experiments on the action
of alkali on conessine dimethosulphate and obtained a very hygroscopic, crystalline base, C,,H,,N,;
this is apparently a dimethyl
derivative of conessine formed by the Loss of 2 niols. of water from
the ammonium base which is evidently the first product of the
In the preparation of conessine dimethosulphate (compare Giemsa
and Malberkann, loc. cit.), in addition to the crystalline dimethosulphate,
a thick, extremely hygroscopic oil was obtained u,hich, on treatment
with alkali, gave a 6nse for which a simple formula could not be
found ; pojsibly this was due to the presence of some impurity, but
we cou!d not repeat the preparation.
The finely-crushed seeds of H. ankdysenterica (500 g.) were
extracted in a copper Soxhkt apparatus with light petroleum (b, p.
40-60") to remove the fixed oil (19 per cent.), and having been freed
from solvent by a current of air, were mixed with inilk of lime (CaO,
loo g.). T h e whole was exposed to the air over-night and then
extrxted with 88 per cent. alcohol for about 18 hours. The deep
brown extract was freed from alcohol by distillation, finally under
diminished pressure, and the residue shaken with dilute hydrochloric
acid. Ether removed non-basic impurities from the filtered acid
solution, from which ammonia then precipitated the crude alkaloid.
This was extracted with ether, and from the dried extract the alkaloid
was obtained as a viscid, brown oil which partly crystal!ised on keeping (yield r per cent.). The oil, dissolved in the minimum quantity
of alcoho!, was warmed with a concentrated alcoholic solution of
sufficient oxalic acid for the formation of the hydrogen oxalate. The
salt crystallised in colourless prisins on cooling and was recrystallised
from alcohol. ' T h e recovered base melted at I 20-1 2 I", and a t 1 2 9
after crystallisation from acetone (Found : C , 80.6 ; H, r r .4. Calc. :
C, 8 0 0 ; H, 21.3 per cent.).
Conessine was not attacked when boiled in sulphuric acid solution
for some time with manganese dioxide. I t was, however, slowly
converted by an acetic acid solution of mercuric acetate into a base
'Since crystailisation OF the base from acetone is alaays accompnnied by considerable
loss of m m r i a l , whsn workmg with large qnantities it is more convenient to recrystallise the
hydrogen oxalaie ; the base h then readily obtained pure enough for experimental PurPOSes
and daes not require to be reaystallised.
which crpstallised from dilute alcohol in fine needles.
would appear to be worihy of iurther investigation.
This rc;ciion
apoCoiscssziu.--A solution oi coriessine dirnethiodide (55 g.) in
water (400 c.c.1 was shaken with an excess ol freshly-precipitaled
silver oxide, the silver iodide and the excess of the oxide wore
removed, and the colourless filtrate was evaporated on the water-bath.
The concentrated, faintly yellow so1u:ion was heated uuder diminished
pressure, finally at 200', vigorous fl-otl~ii~g
taking place. Tl-.e deep
brown, viscid oil thus obtained was dissolved in chloroiorm, filtered
flmx a little carbonaceous matter, and the solvent removed. T h e
residual oil o n trituration with a little alcohol rapidly crystallised, and
on recrysta!iisation from absolute alcohol apocomssi'rzc was obtained in
needles several centirnetres in length ; m. p. 63.5" (Found : C, 34.9 ;
H , 10.6 ; N, 5'0. C,,H,N requires C, 84.9 ; H, 10.6 ; N, 4.5 per
cent.). T h i s base is insoluble in water, very sparingly soluble in cold
alcohol, and more readily soluble in hot. It is readily soluble in
benzene, chloro(orm, or ethyl acetate, and somewhat readily soluble
in light petroleum. i t s port-wine coloured solution in concentratecl
sulphusic acid becomes colourless on the addition of water.
dissolves in nitric acid with a deep red colour, which rapidly changes
to yellow.
T h e Aydmchbrid~ and /zl~rdYodromirte were sparingly soluble,
amorphous solids ; the kycdrogez sulphate, which was readily soluble
i n hot water, much more sparingly soluble in cold, crystallised in
glistening leaflets, m. p. 107-1o8". T h e salt crystaliised apparently
with 78 mols. of water of crystallisation (Found : H,O, 11.0. C,,H,N,
H,SO,, 7hH,O requires 3 b I i 2 0 , 11.6 per cent.), 3g of which were lost
on drying in a vacuum (Found: S, 6 . 4 C,,I-I,N, H,SQ>,, 4i-120
requires S , 6,6 per cent.). After drying, the salt began to soften
at 133", gradually darkened and decomposed, but was not completely
liquid at 280".
T h e picvate crystallised from alcohol in fine, yellow needles, m. p.
requires C , 62.2 ;
(Found : C, 62.0 ; h', 7.0. C,W,,O,N,
H, 6.7 per cent.). The metl~iodicdewas prepared by heating a rnixtci-e
of the base ( I g.), methyl alcohol (5 c.c.), and methyl iodide ( I g.)
in a sealed tube at roo" for 3 hours. It separated on cooling, and
more was obtained on evaporation of the mother-liquor. I t crystalliseci
from ethyl acetate-methyl alcohol in prismatic needles ; these sinkred
at 245" to a viscid resin which became clear at 283-285' (Found :
the rnethiodide
I, 28.1. C,I.I,NI requires I, 28.0 per cent.). \!!hen
was treated with silver oxide in aqueous solution, n$oconessi~ie ivas
r 10-1
The alcoholic filtrate from which npoconessine had been separated
(see p. 2125) +lded, on removal of the solvent, a viscid, uncrystaliisable oil. This was dissolved in an excess of dilute 1-~~drochioric
(1 : 21, the small quantity of a#oconessir,e hydrochloride that separated
was filtered off, and the base recovered from the filtrate. It had
b, p. 2 5 3 - 2 j j o ] ~ ~mm. and was a faintly yellow oil which slowly
crystall;sed at oo in fine needles. I t was readily soluble in all the
ordinary solvents and its aqueous solution showed very strong
fluorescence. The salts with organic and inorganic acids were readily
soluble in water. T h e picrate was obtained crystalline from ethereal
solution, but it was not possible to investigate this method of
Comssi~zeDztnetho~ul$hate.-The base ( 5 g.) and methyl sulphate
(5.6 g.) reacted so vigorously in methyl alcohol ( j c.c.) that the
mixture boiled. After about 5 minutes the dimethosulphate began
to crystallise in well-formed prisms and after r hour acetone ( j c.c.)
was added and the crystailine solid collected (yield 6.3 g.) ; more
was obtained (2.6 g.) on evaporating the mother-liquor in a vacuum.
'The. filtrate, after complete removal of the solvent, yielded a viscid,
semi-crystalline oil which was extremely hygroscopic and resisted
ail attempts a t purification. T h e dimethosulphate, after repeated
crystaliisation from methyl alcohol-acetone, was obtained in glistening
prisms which softened a t 225' and melted a t 240-242" with slight
darkening but no decomposition. T h e prisms effloresced wheu dried
over sulphuric acid (Found : S, 10.6. Calc. : S, 10.5 per cent.).
Actio~zof Potassium Nydroxide oorz Conessim Dimethosulphate.-T h e dimethosulphate (6.3 g.) and potassium hydroxide (25 g.) in
aqueous solution were heated on the water-bath, a slow stream of air
being passed over the solution and through a n absorption apparatus
containing dilute hydrochloric acid. T h e hydrochloric acid solution,
on subsequent evaporation, yielded no residue, and apparently no
volatile base was formed. After 3 hours the pale brown alkaline
solution was concentrated on rhe water-bath ; a smail amount of a
brown oil then separated which was removed i n chloroform. (The
extract on evaporation yielded 0.5 g. of a brown resin which was not
examined.) T h e aqueous solution, now colourless, was saturated with
carbon dioxide and evaporated first on the water-bath and finally to
dryness in a vacuum desiccator over suiphuric acid, T h e crystalline
residue was ground with methyl alcohol, the solution filzered from
inorganic matter, and the solvent reinoved, the treatment being
repeated until the crystalline residue was completely soluble in cold
methyl alcohol.
The bnse remaining after the removal of the alcohol crystallised
in needles, but was extremely hygroscopic. It was insoluble in
The hygroscopic. oil oiitninetl c!uring several preparations of the
diinethosulphnle (sce jr. I I 2 6 ) vias treated with potassium hydroxide
in the way desciilx i n i ~ o v t r . T h e viscid, brown oil that separated
from the concentratctl aque:rus soluticrn mas taken up with chloroform.
On removal of tllc scrlvcnt R crystaliiue solid remained which, after
repeated cqsiaiiisation :ram acetone-benzene, was obtained in
colourless, silky needies : t l ~ c s crapidly became brown on exposure to
the air. As only n s n ~ n l l quantity of material was available, it is
possible that the sui,stanc~:was not obtained quite free from the large
amount of resinous ilnpurity which accompanied it. It melted at
253-254" after siritcri~lgnt s j r ' , , was readily soluble in water, and its
aqueous solutiorr sl~orveda marked fluorescence (Found : C, 63.9,
63.7 ; H, 8 7 , 8.8 ; N, 9.796). T h e p i c ~ & crystallised from alcohol in
small, yellow plates, :ii.:.oin!,. d m u t z50", but it was not prepared in
sufficient quantity for anaiysis.
[Accepted, 21-ro-261.
Depart?mnt o f Organic ChemisLry,
In&# /nst&te of science,