Improvements in the Manufacture or Preparation of Alkylized Uric Acids.
Year: 1899

page_text: Date of Application, 24th Jan., 1899-Accepted, 5th Aug., 1899
COMPLETE SPECIFICATION.
Improvements in the Manufacture or Preparation of Alkylized
Uric Acids.
I, GEORGE WILLIAM JOHNSON, of 47, Lincoln's Inn Fields, in the County of
London, Patent Agent, do hereby declare the nature of this invention (which
has been communicated to me from abroad by C. F. Boehringer & Soehne, of
Waldhof, near Mannhein, in the German Empire,) and in what manner the same is
to be performed to be particularly described and ascertained in and by the
following statement :-
This invention relates to the manufacture or preparation of alkyl-derivatives of
uric acid proper, or in other words of alkyl-uric acids, with particular reference to
obtaining such alkyl-derivatives by direct methods.
Hitherto only the following members of the isomeric series of mono-methyl- and
dimethyl-uric acids have been obtainable by direct methylation of uric acid.
1. a-monomethyl-uric acid, which according to recent investigations, has the
structural formula corresponding to 3-methyl-uric acid and which has been prepared
by Hill and Mabery (Amer. Chem. Journ., vol. 2, page 305 and Ber. d. Deutsch.
chem. Ges., vol. 9, page 370) and by Emil Fischer (Specifications of Letters
Patent 10005/96, 656/97 and 7341/97).
2nd. 9-methyl-uric acid, prepared by Emil Fischer (Ber. d. d. chem. Ges. vol. 17
p. 1777).
3rd. 3.9-dimethyl-uric acid, prepared by Hill and Mabery and by Emil Fischer
(Specifications of Letters Patent 10005/96, 656/97 and 7341/97).
4th 7.9-dimethyl-uric acid, prepared by Emil Fischer (Ber. d. d. chem. Ges.
vol. 17 p. 1780).
In the course of their researches and investigations in this field, my foreign corre-
spondents have succeeded in providing a method whereby 7-methyl-uric acid and
3.7-dimethyluric acid (which hitherto could be obtained only by indirect methods)
can be prepared directly from uric acid.
This new method, according to this invention, consists broadly in the reduction of
oxymethylene derivatives of uric acids, which compounds together with their modes
of preparation, are set forth in the Specification of my application for Letters Patent
No. 20447/98.
While it is true that the usual alkylising agents, under the most varied conditions,
never act first upon the nitrogen atom occupying the 7 position in the uric acid-
molecule (see the nomenclature adapted by Emil Fischer in Ber. d. d. chem. Ges.
vol. 30, p. 557) still, under the process set forth in the said specification the formic
aldehyde is bound to the uric acid in the 7 position forming 7-oxymethylene-uric
acid. This latter compound my foreign correspondents have found, can, readily, and
directly, be converted into 7-methyluric acid by reduction.
In an analogous manner, and as set forth in the said specification, 7-oxymethylene_
3-methyl-uric acid, which can be converted into 3.7-dimethyl-uric acid, can be

page_text: obtained from the action of formnic-aldehyde on 3-methyl-uric acid. Finally, 7-oxy-
methylene-1.3-dimethyl-uric acid, obtained in the manner described in the said
specification, can be reduced, according to the present invention, to 1.3.7-trimethyl-
uric acid, or hydroxy-caffeine. This reaction, moreover, seems to be susceptible of
a still more general application.
The process of reduction of the oxymethylene-uric acid is best carried out in acid
solutions, such as, for example, hydrochloric acid in conjunction with tin. Such
reduction takes place according to the formula
As the initial material in the manufacture of this uric acid 3-methyl-7-oxymethylene
uric acid, is employed. Its preparation and characteristics are described in the
Specification of the aforesaid application for Letters Patent 20447/98..
Take one part of this 3-methyl-7-oxymethylene-uric acid and dissolve it in eight
parts of fuming hydrochloric acid, and add to the solution from five to six parts of
tin. This mixture is allowed to stand whilst being cooled with ice water. After the
reduction, under these conditions, has taken place for about 20 hours the separation
of the 3.7-dimethyl-uric acid formed begins, it being precipitated in the form of
coarse granular crystals. As soon as the evolution of hydrogen gas becomes less
energetic it is accelerated by the introduction of some gaseous hydrochloric acid.
After the lapse of about 40 hours the liquor is passed off from the undissolved
tin and diluted with water. The dimethyl uric is thus precipitated in the form of
crystals from which the mother liquor is removed in any suitable manner, such as by
draining siphoning or decanting. After redissolving the said crystals in dilute
ammonia solution and treatment with carbon and finally precipitating with hydro-
chloric acid the pure 3.7-dimethyl-uric acid is obtained, it corresponding in every
respect to the body described in Ber. d. deutsch. chem. Ges. vol. 28, p. 2482.

page_text: EXAMPLE III.
PREPARATION OF 1.3.7-TRIMETHYL-URIC ACID (HYDROXYCAFFEINE).
In this process there is also employed, as initial material, a body described in the
aforesaid Specification of the application for Letters Patent 20447, 1898 viz.
1.3-dimethyl-7-oxymethylene-uric acid. One part of this acid is dissolved in
5 parts by volume of hydrochloric acid and 5 to 6 parts of tin are added to the
solution. This mixture is allowed to stand while being cooled with ice-water.
After the reduction under these conditions has taken place for about twenty hours, and
after it has been continued at ordinary, or room, temperature for about 20 hours,
the liquor is diluted with about twenty parts of water; and, after filtering from
undissolved tin, is cooled by ice-water for several hours, whereby regenerated
1.3-dimethyl-uric acid is precipitated.
After removing the crystals of the acid the liquor is evaporated, on the water-
bath, as nearly as possible to dryness. The residue is taken up with about 10 parts
of cold water and the colourless liquor is allowed to stand for some time, whereby
1.3.7-trimethyl-uric acid, or hydroxycaffeine, crystallizes out in the form of fine
needles.
The remainder of the hydroxy-caffeine is obtained by extraction by means of a
suitable solvent, such for example as chloroform.
The compound so obtained possesses all the characteristic properties which
have been enumerated for this acid in Liebig's Annalen vol. 215, p. 268.
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
The manufacture, or preparation, of alkylized uric acids by acting upon an
oxymethylene-uric acid by a reducing agent as herein before explained.
1000
of January 1900
JOHNSONS & WILLCOX,
47, Lincoln's Inn Fields, London, W.C., Agents.