Improvements in the Manufacture, or Preparation, of Paraxanthine and Intermediate Products relating thereto.
Year: 1898

page_text: Date of Application, 12th Dec., 1898-Accepted, 11th Feb., 1899
COMPLETE SPECIFICATION.
Improvements in the Manufacture, or Preparation, of Paraxanthine
and Intermediate Products relating thereto.
I, JAMES YATE JOHNSON, of 47, Lincoln's Inn Fields, in the County of London,
Gentleman, do hereby declare the nature of this invention (which has been
communicated to me from abroad by C. F. Boehringer & Soehne, of Waldhof, near
Mannheim, in the Empire of Germany) and in what manner the same is to be
performed, to be particularly described and ascertained in and by the following
statement:—
It has been shewn by, E. Fischer, in the Berichte d. d. chem. Gesallschaft
28,2481 &c. that caffeine and theobromine, on treatment with phosphorus penta-
chloride, are, in part, demethylated, with simultaneous substitution of chlorine.
In this way caffeine is converted first into chloro-caffeine; the latter then loses
two methyl groups, which are eliminated in the form of methylic chloride, and
passes into 7-methyl-2: 6: 8-trichloropurine.
My foreign correspondents have succeeded in diverting the course of the above
reaction into a somewhat different direction by treatment with about equi-molecular
proportions of PC, whereby they have found that it is possible to eliminate one
methyl group only from caffeine and from chlorocaffeine, namely the methyl gronp
attached to nitrogen atom 3.
In this manner the hitherto unknown chloroparaxanthine is produced, which can
be readily converted into paraxanthine by means of reducing agents.
In the above reaction the methyl group attached to nitrogen atom 3 is not
eliminated as methylic chloride, an intermediate compound being first formed, the
said compound containing chlorine and having the formula C₂H₂N,O₂Cl₂, which

page_text: arises from the chlorinating action of phosphorous pentachloride on the methyl group
attached to nitrogen atom 3, according to the equation

page_text: PREPARATION 31: 8 DICHLOROCAFFEINE.
.
23 parts of dried chlorocaffeine are heated, in an autoclave, with 30 parts,
(1 molecular proportions), of phosphorus pentachloride and 170 parts of
phosphorus oxychloride at from 150° to 155° Centigrade, for from 8 to 9 hours. In
place of the phosphorus oxychloride other solvent such as chloroform can be used.
There is no pressure in the vessel on cooling, and a reddish-brown liquid has been
produced, in which colourless needles are suspended.
:
The whole product is evaporated to small bulk in vacuum, a tough, reddish-brown,
resin being obtained as residue. The solution in ether, on standing for a considerable
time, yields a slightly coloured crystalline mass, which is treated with a small
quantity of cold benzene, pumped, and redissolved in warm ether.
In this way 3: 8 dichlorocaffeine is obtained in colourless, lustrous, well-formed,
crystals, which give figures agreeing with the formula C₂HNO₂Cl₂.
Dichlorocaffeine melts at 144°-145.5° Centigrade to a colourless liquid, and gives
the murexide test with chlorine water.
It is readily soluble in cold chloroform, acetone, ethylic acetate, benzene, warm
ether, and alcohol, but is less readily soluble in cold water.
On boiling it with alcohol, or water, hydrochloric acid is eliminated, and
31-oxy-8-chlorocaffeine, or its derivatives, produced.
PREPARATION OF CHLOROPARAXANTHINE OR 1:7 DIMETHYL-8-CHLOROXANTHINE.
In preparing chloroparaxanthine it is not necessary to use pure dichlorocaffeine,
which is obtained crystalline with some difficulty, but the crude residue from
evaporating the phosphorus oxychloride solution can be boiled with 30 parts of
water until formaldehyde is no longer evolved. Undissolved resin is then removed
by filtration, and the solution is treated with charcoal and evaporated to half its
bulk. As the liquid cools, chloroparaxanthine slowly crystallises in nodular
aggregates of small slender needles; it is purified by means of the well crystallised
sodium salt, and redissolved in boiling water.
It is obtained in slender, colourless needles which on analysis give figures
agreeing well with the formula C,H,NO₂CI.
Chloroparaxanthine gives the murexide test very distinctly with chlorine water,
or dilute nitric acid.
It sinters towards 270° Centigrade when quickly heated, and melts to a colourless
liquid at 281° Centigrade evolving gas. It dissolves somewhat readily in boiling
alcohol and moderately in boiling water and chloroform; it is readily soluble in
dilute ammonia and dilute alkalies. Concentrated caustic alkalies, particularly
caustic soda, immediately precipitate the alkali salt in small, slender, lustrous
needles.
Chloroparaxanthine also dissolves readily in concentrated hydrochloric acid and
is quickly precipitated from the solution by water.

page_text: PREPARATION OF PARAXANTHINE.
This is
1 part of chloroparaxanthine is heated on the water bath with 5 parts of fuming
hydriodic acid, (of a specific gravity of 1.96), and some phosphonium iodide, with
continuous agitation, until an almost colourless solution is produced.
evaporated to dryness on the water bath, and the residual paraxanthine hydriodide
repeatedly evaporated with water in order to completely remove hydriodic acid; it
is then dissolved in ammonia, and again evaporated to dryness. On treatment
with cold water free paraxanthine remains undissolved, and, after crystallisation
from water, is found to exhibit the characteristic properties ascribed to it (Ber. d. d.
chem. Gesell. 30,2408).
Having now particularly described and ascertained the nature of this invention
and in what manner the same is to be performed, I declare that what I
claim is :-
__
1. The manufacture, or preparation, of paraxanthine by treating caffeine with
phosphorus pentachloride, in the proportions above given, then heating the
31-8-dichlorocaffeine, thus formed, with water, whereby 8-chloroparaxanthine arises,
and finally reducing the latter.
2. As a
described.
new article of manufacture the 31-8-dichlorocaffeine hereinbefore
3. As a new article of manufacture the 8-chloroparaxanthine hereinbefore
described.
Dated this 12th day of December 1898.
JOHNSONS & WILLCOX,
47, Lincoln's Inn Fields, London, W.C., Agents.