Improvements in the Production of Oxypurines and their Alkyl Derivatives from Trichloropurine.
Year: 1897

page_text: Date of Application, 9th Oct., 1897
Complete Specification Left, 7th July, 1898--Accepted, 8th Oct., 1898
PROVISIONAL SPECIFICATION.
Improvements in the Production of Oxypurines and their Alkyl
Derivatives from Trichloropurine.
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 com-
municated to me from abroad by C. F. Boehringer & Soehne, of Waldhof, near
Mannheim, in the Empire of Germany) to be as follows :-
In both of the known methyltrichloropurines (Report of the "Chem. Ges."
17,331 and 28,2488) the chlorine occupying the position 8 is always first separated
by alkali, so that the synthetic production of xanthine derivatives in this way has
not hitherto been effected. The case is however different with regard to non-
methylated trichloropurine. This as a strong acid, forms stable alkali salts, whereby
the action of the 3 atoms of chlorine is so modified that, on heating with alkali, the
chlorine atom occupying the position 6 (and not that occupying the position 8) is
first separated and replaced by oxygen, and therefore on using. alcoholic alkali,
under moderate temperature, there is obtained from trichloropurine: (6)-ethoxy-(2-8)
dichloropurine having the formula :-
Improvements in the Production of Oxypurines and their Alkyl
Derivatives from Trichloropurine.
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 com-
municated to me from abroad by C. F. Boehringer & Soehne, of Waldhof, near
Mannheim, in the Empire of Germany) to be as follows :-
In both of the known methyltrichloropurines (Report of the "Chem. Ges."
17,331 and 28,2488) the chlorine occupying the position 8 is always first separated
by alkali, so that the synthetic production of xanthine derivatives in this way has
not hitherto been effected. The case is however different with regard to non-
methylated trichloropurine. This as a strong acid, forms stable alkali salts, whereby
the action of the 3 atoms of chlorine is so modified that, on heating with alkali, the
chlorine atom occupying the position 6 (and not that occupying the position 8) is
first separated and replaced by oxygen, and therefore on using. alcoholic alkali,
under moderate temperature, there is obtained from trichloropurine: (6)-ethoxy-(2-8)
dichloropurine having the formula:-
CI.C
N
=
COC₂H
NKH
C.CI
When this is heated with hydrochloric acid, it loses the ethyl group and changes,
into (6)-oxy-(2-8)-dichloropurine, from which, by reduction, (6)-oxypurine is
obtained, which has proved to be identical with native hypoxanthine.
The splitting off of the ethyl, and the replacement of the chlorine atoms, by
hydrogen, and the formation of hypoxanthine can be effected in one operation by
treating the (6)-ethoxy-(2.8)-dichloropurine with bydriodic acid.
On causing alcoholic alkali to act at an elevated temperature upon trichloropurine,
a second atoin of chlorine is also eliminated, namely that occupying the position 2,
80 that there is formed the (8)-chloro-(2.6)-diethoxypurine, having the
formula —

page_text: HNC - N
identical with the native xanthine is obtained.
During the action of hydriodic acid, also in the case of the (8)-chloro-(2.6)
diethoxypurine, the splitting off of the ethyl groups and the reduction of the
chlorine, take place simultaneously, whereby, as in the above case, xanthine results.
The same process may further be advantageously employed for preparing the
alkyl derivatives from hypoxanthine and xanthine, this being effected by first
alkylating the chlorine compounds, resulting as intermediate products, and only
subsequently reducing them. Thus by treating the aqueous alkaline solution with
halogen methyl, from the (6)-oxy (2.8)-dichloropurine, the (1.7)-dimethyl-(6)-oxy-
(2.8)-dichloropurine is formed, which then, by reduction with bydriodic acid, is
transformed into dimethylhypoxanthine already produced in a different way by
Krüger (Zeitschrift für physiologische Chemie 18,436). In the same manner
chlorocaffeine is obtained from the (2.6)-dioxy (8) chloropurine by means of
methylation in an alkaline solution.
1. PRODUCTION OF (2.8)-DICHLORO-(6)-ETHOXYPURINE AND (8)-CHLORO-(2.6)-
DIETHOXYPURINE.
To a solution of 1.2 parts (the parts are by weight) of sodium in 24 parts of
alcohol, cooled down to ordinary atmospheric temperature, is added a rapidly cooled
solution of four parts of dry trichloropurine in 16 parts of alcohol, a clear, and
faintly yellow liquid, is produced, which becomes spontaneously heated to about
30 degrees Centigrade and which is soon rendered turbid by common salt. After
the mixture has been allowed to stand for 3 hours at ordinary temperature, water
is added and the solution is slightly supersaturated with acetic acid and the alcohol
is vapourized, the dichloroethoxypurine precipitating in the form of colourless, and
highly flexible needles, which are re-crystallized from hot benzene. It has the
formula C,H&CNO; and fuses at a temperature of about 190 degrees Centigrade
and completely inelts and decomposes at about 200 degrees Centigrade.
It dissolves with great difficulty in hot water but is very readily soluble in hot
alcohol and acetone.
On using a methylalcoholic solution instead of the ethylalcoholic solution of
sodium, then, under otherwise equal conditions, the (2.8)-dichloro-(6)-methoxy-
purine is formed, which melts and simultaneously decomposes at a temperature of
about 225 degrees Centigrade and which dissolves with far greater difficulty in
benzene, than does the ethoxy compound.
On being heated with surplus sodium ethylate, the dichlorethoxypurine changes
into the (8)-chloro-(2-6)-diethoxypurine. In order to directly produce the same
from trichloropurine, the latter with a concentrated alcoholic solution of surplus
sodium ethylate is heated for 3 hours, in a closed vessel, to 100 degrees Centigrade,
the alcohol is then evaporated, the residue dissolved in water and the yellow liquid
supersaturated with acetic acid. In this operation the chloro-diethoxypurine
precipitates in the form of a voluminous mass consisting of fine needles. The
substance has the formula:-CHдNCI O₂ and is very similar to the monoethoxy
compound. It fuses at about 190. degrees Centigrade and melts at about

page_text: cause it to readily dissolve.
2. PRODUCTION OF (6)-OXY-(2.8)-DICHLOROPURINE.
If the pulverized (6)-ethoxy-(2.8)-dichloropurine be heated with five times the
quantity of fuming hydrochloric acid, on the water bath, it rapidly enters into
solution, and the separation of the slowly dissolving (6)-oxy-(2.8)-dichloropurine,
in the form of thick crystals, very readily takes place. After a half hours heating
the saponification is finished. The product is then diluted with water, allowed to
cool down, and filtered.
To effect its complete purification, it is transformed into a potassium salt, which,
by recrystallization from hot water with the addition of a small quantity of animal
charcoal, can be discoloured. The oxydichloropurine, regenerated from the
potassium salt, forms beautiful colourless needles of the formula:-С¿H₂С₁₂NO.
When heated above 350 degrees Centigrade it decomposes while simultaneously
assuming a brown colour. In hot water it dissolves with great difficulty. It is
more readily soluble in hot alcohol. Its aqueous solution has an acid reaction and
decomposes the carbonates. The barium salt is crystallised from the hot solution
in surplus baryta-water, in the form of minute clusters, or bundles of needles.
Nitrate of silver in the ammoniacal solution produces a colourless amorphous
precipitate.
3. TRANSFORMATION OF THE (6)-OXY-(2.8) DICHLOROPURINE INTO
HYPOXANTHINE.
The finely pulverized chlorine compound is added to ten times the quantity, by
weight, of hydriodic acid of a specific gravity of 1.96 and after the addition of
phosphonium iodine, or yellow phosphorus, it is first agitated for about one hour at
ordinary temperature and subsequently heated on the water-bath, until an almost
colourless solution is produced. On cooling down, the hypoxanthine hydriodide
separates in the form of beautiful crystals, and is obtained in its entirety by
evaporating the hydriodic acid.
From the concentrated aqueous solution of the hydriodide the hypoxanthine is
precipitated by neutralization with ammonia, and is obtained in its pure state by
recrystallization from hot water, to which animal charcoal has been added. The
artificial product possesses all the properties of the native hypoxanthine.
Instead of using the (6)-oxy-(2.8)-dichloropurine for producing hypoxanthine,
the (2.8)-dichloro-(6) ethoxypurine may be employed, since the latter, when treated
with hydriodic acid under the aforesaid conditions, loses the ethyl as well as the
two chlorine atoms.
4. TRANSFORMATION OF THE (6)-OXY-(2.8)-DICHLOROPURINE IN DIMETHYL
HYPOXANTHINE.
One part of the chlorine compound is dissolved in an amount of normal potash
lye, calculated for two molecules, and after 1 parts of methylic iodide having been
added, it is heated for two hours at a temperature of 80 degrees Centigrade in a
closed vessel and stirred. During this operation the methylic iodide disappears
entirely, whilst the dimethyloxydichloropurine which is insoluble in alkalies,
separates in the form of a slightly coloured crystalline mass. When first
recrystallized from hot alcohol and subsequently from hot water, it forms colourless
needles which generally fuse between 245 and 255 degrees Centigrade.
formula is:
The

page_text: of a specific gravity equal to 1.96, and of surplus phosphonium iodine, it soon dis-
selves, and simultaneously changes into dimethylhypoxanthine, which on evapora-
ting the liquid, remains as a crystallised hydroiodic salt. For the purpose of
purification, it is preferably transformed by sodium iodide into the compound
described by Krüger (Zeitschrift für physiologische Chemie 18,437) by neutralizing
the aqueous solution of the hydriodide with sodium-lye, and evaporating the
product until it crystallizes, and subsequently recrystallizing the crystals from hot
alcohol of 80 per cent. The sodium iodide compound, as well as the base set
free therefrom, are found to be identical with the bodies obtained by Krüger from
the hypoxanthine itself.
ting the liquid, remains as a crystallised hydroiodic salt. For the purpose of
purification, it is preferably transformed by sodium iodide into the compound
described by Krüger (Zeitschrift für physiologische Chemie 18,437) by neutralizing
the aqueous solution of the hydriodide with sodium-lye, and evaporating the
product until it crystallizes, and subsequently recrystallizing the crystals from hot
alcohol of 80 per cent. The sodium iodide compound, as well as the base set
free therefrom, are found to be identical with the bodies obtained by Krüger from
the hypoxanthine itself.
5. TRANSFORMATION OF THE (8)-CHLORO-(2.6)-DIETHOXYPURINE INTO
XANTHINE.
Chlorodiethoxypurine dissolves at ordinary temperature in the presence of ten
times the amount of hydriodic acid of a specific gravity of 1.96, and the reduction
and liberation of iodine commence at once. It is again reduced by adding
pulverized phosphonium iodine, or by agitating with yellow-phosphorus, and, after
the lapse of about one hour, the reduction is completed at an ordinary temperature.
During this most probably the (2.6)-diethoxypurine is generated first and remains in
solution in the hydriodic acid. The same, however, during this operation especially
if comparatively large quantities be employed, undergoes a further change into
xanthine, while the ethyl groups are split up by the strong acid. This second
phase of the reaction at normal temperature, takes place only partially, so that
only comparatively little xanthine hydriodide is precipitated. If however the
product be subsequently heated on ab water bath, the change into xanthine
becomes complete, and its hydriodide precipitates in the form of a thick crystallic
pulp. The hydriodic acid is evaporated, the residue is treated with dilute aqueous
ammonia in slight excess, the separated xanthine is filtered and subsequently,
for the purpose of purification, it is dissolved in a large amount of heated aqueous
ammonia.
On evaporating the base by boiling the xanthine precipitates in the form of a
colourless granular powder. The synthetic product is of the same composition as,
and presents all the known properties of native xanthine.
6. CHANGE OF THE (8)-CHLORO-(2.6)-DIETHOXYPURINE INTO CHLOROXANTHINE AND
CHLOROCAFFEINE.
By heating on a water bath the pulverized chlorodiethoxypurine with five times
the quantity of hydrochloric acid of a specific gravity of 1·19, it first enters into
complete solution and, after a short time, the separation of the very slowly soluble
(8)-chloro-(2.6)-dioxypurine (chloroxanthine) commences. The decomposition is
finished in about half an hour. After the product has been cooled down and diluted
with water, it is filtered. To effect its complete purification, it is transformed into
the beautifully crystallizing sal-ammoniac, and the latter is again separated by means
of acid. The chloroxanthine is of the composition: CHCI NO₂. It dissolves with
great difficulty even in hot water, alcohol and anhydrous vinegar. From the warm
solution of its salts, it is precipitated in the form of a colourless granular crystal-
line mass by means of mineral acids. When heated it carbonizes without
melting. It readily dissolves in concentrated sulphuric acid, and is reprecipi-
tated by water.
The alkali salts are very readily soluble in water. The potassium compound
crystallizes from strong potash lye, in the form of extremely thin and flexible
minute needles. The ammonium salt dissolves with far greater difficulty. On
cooling down its aqueous solution slowly it crystallizes in the form of small, but
beautifully shaped, and apparently rectangular tablets.
Similarly to the xanthine, the chloroxanthine very effectively furnishes the

page_text: murexide proof. By reduction with hydriodic acid, it readily changes into
xanthine.
For obtaining the change into chlorocaffeine two parts of chloroxanthine are
dissolved in such a quantity of normal potash-lye, that the percentage of potash
corresponds to three molecules, and the liquid is agitated for two hours at 80 degrees
Centigrade in a closed vessel, with five parts of methylic iodide. During this
operation, the greater part of the chlorocaffeine separates in the form of thin needles,
which are after cooling separated by filtering and (after washing with highly dilute
soda-lye, which removes a small amount of admixed acid compound,) they are
recrystallized from hot alcohol, or hot water. The product obtained is identical
with the chloro-caffeine, which is formed by the chlorination of native caffeine.
Dated this 9th day of October 1897.
JOHNSONS & WILLCOX,
47, Lincoln's Inn Fields, London, W.C., Agents.
COMPLETE SPECIFICATION.
Improvements in the Production of Oxypurines and their Alkyl
Derivatives from Trichloropurine.
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:-
In both of the known methyltrichloropurines (Report of the "Chem. Ges."
17,331 and 28, 2488) the chlorine occupying the position 8 is always first separated
by alkali, so that the synthetic production of xanthine-derivatives in this way
has not hitherto been effected. The case is however different with regard to non-
methylated trichloropurine. This as a strong acid, forms stable alkali salts,
whereby the action of the 3 atoms of chlorine is so modified that, on heating with
alkali, the chlorine atom occupying the position 6 (and not that occupying the
position 8) is first separated and replaced by oxygen, and therefore on using
alcoholic alkali, under moderate temperature, there is obtained from trichloropurine :
(6)-ethoxy-(2-8)-dichloropurine, having the formula :—

page_text: hydrogen, and the formation of hypoxanthine can be effected in one operation by
treating the (6)-ethoxy-(2.8)-dichloropurine with hydriodic acid.
On causing alcoholic alkali to act at an elevated temperature upon trichloropurine,
a second atom of chlorine is also eliminated, namely that occupying the position 2,
so that there is formed the (8)-chloro-(2.6)-diethoxypurine, having the
formula-
When treated with hydrochloric acid, the latter loses the two ethyl groups and
changes into (2.6)-dioxy-(8)-chloroparine, from which by way of reduction the
(2.6) dioxypurine,
ос
HN
CO
H
N
H
<B
HN
. C
identical with the native xanthine, is obtained.
During the action of hydriodic acid, also in the case of the (8)-chloro-(2-6)
diethoxypurine, the splitting off of the ethyl groups and the reduction of the chlorine
take place simultaneously, whereby, as in the above case, xanthine results.
The same process may further be advantageously employed for preparing the
alkyl-derivatives from hypoxanthine and xanthine, this being effected by first
alkylating the chlorine compounds, resulting as intermediate products, and only
subsequently reducing them. Thus by treating the aqueous alkaline solution with
halogen methyl, from the (6)-oxy (2.8)-dichloropurine, the (1.7)-dimethyl-(6)-oxy-
(2.8)-dichloropurine is formed, which then, by reduction with hydriodic acid, is
transformed into dimethyl-hypoxanthine already produced in a different way by
Krüger (Zeitschrift für physiologische Chemie 18,436). In the same manner
chloro-caffeine is obtained from the (2.6)-dioxy (8) chloropurine by means of
methylation in an alkaline solution.
1. PRODUCTION OF (2.8)-DICHLORO-(6) ETHOXY-PURINE AND (8)-CHLORO-(2.6)-
DIETHOXYPURINE.
To a solution of 1.2 parts (the parts are by weight) of sodium in 24 parts of
alcohol, cooled down to ordinary atmospheric temperature, is added a rapidly cooled
solution of four parts of dry trichloropurine in 16 parts of alcohol, a clear, and
faintly yellow, liquid is produced, which becomes spontaneously heated to about
30 degrees Centigrade and which is soon rendered turbid by common salt. After
the mixture has been allowed to stand for three hours at ordinary temperature,
water is added and the solution is slightly supersaturated with acetic acid and the
alcohol is vapourized, the dichloroethoxypurine precipitating in the form of colour-
less, and highly flexible, needles, which are re-crystallized from hot benzene. It
has the formula CHCI,NO, and fuses at a temperature of about 190 degrees
Centigrade and completely melts and decomposes at about 200 degrees Centigrade.

page_text: If the pulverized (6)-ethoxy-(2.8)-dichloropurine be heated with five times the
quantity of fuming hydrochloric acid, on the water bath, it rapidly enters into
solution, and the separation of the slowly dissolving (6)-oxy-(2.8)-dichloropurine in
the form of thick crystals, very readily takes place. After a half hour's heating
the saponification is finished. The product is then diluted with water, allowed to
cool down, and filtered.
To effect its complete purification, it is transformed into a potassium salt, which,
by re-crystallization from hot water with the addition of a small quantity of animal
charcoal, can be discoloured. The oxydichloropurine, regenerated from the potassium
salt, forms beautiful colourless needles of the formula:-CH₂C₁₂NO. When
heated above 350 degrees Centigrade it decomposes while simultaneously assuming
a brown colour. In hot water it dissolves with great difficulty. It is more readily
soluble in hot alcohol. Its aqueous solution has an acid reaction and decomposes the
carbonates. The barium salt is crystallized from the hot solution in surplus baryta-
water, in the form of minute clusters, or bundles, of needles. Nitrate of silver in
the ainmoniacal solution produces a colourless amorphous precipitate.
The (6)-oxy-(2.8)-dichloropurine may also be obtained directly from the
trichloropurine by heating the latter with an aqueous solution of alkali. The
chlorine atom (6) is in this manner readily replaced by the hydroxyl-group.
For example, an amount of trichloropurine is dissolved in sufficient potash-lye to
make the amount of alkali correspond to three molecules. The liquid is then heated
to 100° Centigrade, and maintained at this temperature for about 3 hours. The
solution thus acquires a pale pink colour. It is then supersaturated with
hydrochloric acid, whereby the (6)-oxy-(2.8)-dichloropurine is thrown out in the form
of fine reddish acicular crystals. The further purification is carried out in the
manner already described.
3. TRANSFORMATION OF THE (6)-OXY-(2.8)-DICHLOROPURINE INTO HYPOXANTHINE.
The fiuely pulverized chlorine compound is added to ten times the quantity, by
weight, of hydriodic acid of a specific gravity of 1.96 and, after the addition of
phosphonium iodide, or yellow phosphorus, it is first agitated for about one hour.
at ordinary temperature and subsequently heated on the water bath, until an almost

page_text: colourless solution is produced. On cooling down, the hypoxanthine hydriodide
separates in the form of beautiful crystals, and is obtained in its entirety by
evaporating the hydriodic acid.
From the concentrated aqueous solution of the hydriodido the hypoxanthine is
precipitated by neutralization with ammonia and is obtained in its pure state by
re-crystallization from hot water, to which animal charcoal has been added. The
artificial product possesses all the properties of the native hypoxanthine.
Instead of using the (6)-oxy-(2-8)-dichloropurine for producing hypoxanthine,
the (2-8)-dichloro-(6)-ethoxypurine may be employed, since the latter, when treated
with hydriodic acid, under the aforesaid conditions, loses the ethyl as well as the two
chlorine atoms.
evaporating me nyurionic actu.
From the concentrated aqueous solution of the hydriodide the hypoxanthine is
precipitated by neutralization with ammonia and is obtained in its pure state by
re-crystallization from hot water, to which animal charcoal has been added. The
artificial product possesses all the properties of the native hypoxanthine.
Instead of using the (6)-oxy-(2-8)-dichloropurine for producing hypoxanthine,
the (28)-dichloro-(6)-ethoxypurine may be employed, since the latter, when treated
with hydriodic acid, under the aforesaid conditions, loses the ethyl as well as the two
chlorine atoms.
4. TRANSFORMATION OF THE (6)-OXY-(2.8)-DICHLOROPURINE INTO DIMETHYL
HYPOXANTHINE.
One part of the chlorine compound is dissolved in an amount of normal potash-lye
calculated for two molecules, and after 1 parts of methylic iodide having been
added, it is heated for two hours at a temperature of 80 degrees Centigrade in a
closed vessel and stirred. During this operation the methylic iodide disappears
entirely, whilst the dimethyloxydichloropurine, which is insoluble in alkalies,
separates in the form of a slightly coloured crystalline mass. When first
re-crystallized from hot alcohol and subsequently from hot water, it forms colourless
needles which, generally, fuse between 245 and 255 degrees Centrigade. The
formula is C,HC₁₂NO. If agitated at ordinary temperature, with ten times the
quantity of hydriodic acid of a specific gravity equal to 1.96 and of surplus
phosphonium iodido, it soon dissolves and simultaneously changes into dimethyl-
hypoxanthine which, on evaporating the liquid, remains as a crystallized hydroiodic
salt. For the purpose of purification, it is preferably transformed (by sodium iodide)
into the compound described by Krüger (Zeitschrift für physiologische Chemie
18,437) by neutralizing the aqueous solution of the hydriodide with sodium-lye, and
evaporating the product until it crystallizes, and subsequently re-crystallizing the
crystals from hot alcohol of 80 per cent. The sodium iodide compound, as well as
the base set free therefrom, are found to be identical with the bodies obtained by
Krüger from the hypoxanthine itself.
5. TRANSFORMATION OF THE (8)-CHLORO-(2.6)-DIETHOXYPURINE INTO XANTHINE.
Chlorodiethoxypurine dissolves, at ordinary temperature, in the presence of ten
times the amount of hydriodic acid of a specific gravity of 1.96, and the reduction
and liberation of iodine commence at once. It is again reduced by adding
pulverized phosphonium iodide or by agitating with yellow phosphorus, and, after
the lapse of about one hour, the reduction is completed at an ordinary temperature.
During this most probably the (2.6)-diethoxypurine is generated first and remains
in solution in the hydriodic acid. The same, however, during this operation,
especially if comparatively large quantities be employed, undergoes a further change
into xanthine, while the ethyl groups are split off by the strong acid. This second
phase of the reaction, at normal temperature, takes place only partially, so that only
comparatively little xanthine hydriodide is precipitated. If however the product be
subsequently heated on a water bath, the change into xanthine becomes complete
and its hydriodide precipitates in the form of a thick crystallic pulp. The hydriodic
acid is evaporated, the residue is treated with dilute aqueous ammonia in slight
excess, the separated xanthine is filtered and subsequently, for the purpose of
purification, it is dissolved in a large amount of heated aqueous ammonia.
On evaporating the base by boiling the xanthine precipitates in the form of a
colourless granular powder. The synthetic product is of the same composition as,
and presents all the known properties of native xanthine.

page_text: 6. CHANGE OF THE (8)-CHLORO-(2.6)-DIETH-OXYPURINE INTO CHLOROXANTHINE AND
CHLOROCAFFEINE.
By heating on a water bath the pulverized chlorodiethoxypurine with five times
the quantity of hydrochloric acid of a specific gravity of 1·19, it first enters into
complete solution and, after a short time, the separation of the very slowly soluble
(8)-chloro-(2-6)-dioxypurine (chloroxanthine) commences. The decomposition is
finished in about half an hour. After the product has been cooled down and
diluted with water, it is filtered. To effect its complete purification, it is
transformed into the beautifully crystallizing ammonium salt, and the latter is again
separated by means of acid. The chloroxanthine is of the composition:
CH,CÍ NO, It dissolves with great difficulty even in hot water, alcohol and
anhydrous acetic acid. From the warm solution of its salts it is precipitated in the
form of a colourless granular crystalline mass by means of mineral acids. When
heated it carbonizes without melting. It readily dissolves in concentrated sulphuric
acid and is re-precipitated by water.
The alkali salts are very readily soluble in water. The potassium compound
crystallizes from strong potash lye in the form of extremely thin and flexible
minute needles. The ammonium salt dissolves with far greater difficulty. On
cooling down its aqueous solution slowly it crystallizes in the form of small, but
beautifully shaped, and apparently rectangular, tablets.
Similarly to the xanthine, the chloroxanthine very effectively furnishes the
murexide proof. By reduction with hydriodic acid it readily changes into
xanthine.
For obtaining the change into chlorocaffeine two parts of chloroxanthine are
dissolved in such a quantity of normal potashi-lye, that the percentage of potash
corresponds to three molecules, and the liquid is agitated for two hours at 80
degrees Centigrade in a closed vessel, with five parts of methylic iodide. During
this operation the greater part of the chlorocaffeine separates in the form of thin
needles, which are after cooling, separated by filtering and (after washing with
highly dilute soda lye, which removes a small amount of admixed acid compound)
they are recrystallized from hot alcohol, or hot water.
The product obtained is identical with the chlorocaffeine, which is formed by the
chlorination of native caffeine. In the foregoing examples it is to be understood
that an alcoholic solution of caustic alkali may, where suitable, be used instead of
a solution of an alkali metal in alcohol, but it is preferred to use the latter.
Having now particularly described and ascertained the nature of this inven-
tion and in what manner the same is. to be performed, I declare that what I
claim is :-
1. The manufacture or preparation of hypoxanthines and xanthines, alkylized or
free from alkyl, by treating trichloropurine with an alcoholic or aqueous solution of
alkali, then after the elimination if necessary of the ethyl-groups reducing the
resulting chloro-compounds, with or without the intervention of alkylizing reagents,
substantially as described.
2. The manufacture or preparation of hypoxanthine and alkylized hypoxanthines
by treating trichloropurine with an aqueous solution of alkali, whereby (6)-oxy-(2.8)-
dichloropurine is obtained, then reducing the same, with or without the foregoing
intervention of alkylizing reagents, substantially as described.
3. The manufacture or preparation of xanthine by heating trichloropurine with an
alcoholic solution of alkali, then treating the 8-chloro-2-6-diethoxypurine obtained,
with hydriodic acid, substantially as described.
4. The manufacture or preparation of alkylized xanthines by heating trichloro-
purine with an alcoholic solution of alkali, treating the resulting compound with

page_text: hydrochloric acid, then alkylizing and finally reducing the alkylized chlorodioxy-
purine by treatment with hydriodic acid, substantially as described.
5. The production of oxypurines and their alkyl derivatives substantially as
described in the foregoing examples.
JOHNSONS & WILLCOX,
47, Lincoln's Inn Fields, London, W.C., Agents.