A Process for the Preparation of Piperidine and Dihydroquinoline.
Year: 1898

page_text: Date of Application, 12th Oct., 1898
Complete Specification Left, 3rd July, 1899-Accepted, 9th Sept., 1899
PROVISIONAL SPECIFICATION.
A Process for the Preparation of Piperidine and Dihydroquinoline.
I, WILHELM PIP, of 611 Karlstrasse, Darmstadt, in the Empire of Germany,:
Doctor of Philosophy, do hereby declare the nature of this invention to be as
follows:
It has before now been attempted to obtain piperidine from pyridine by
electrolysis; yet the attempts made in this direction have proved unavailing
although a clear and definite course of action was indicated for the purpose of
making them successful. The method recommended was as follows: -10 parts
by weight of pyridine was to be dissolved in 100 parts by weight of sulphuric.
acid at 10 per cent., and the resulting solution to be submitted to the action of
electrical current; it being proposed to employ lead plates for cathodes, whilst
forming the anodes of any insoluble material; and the force of the current to
be used being set down at D100 = 12 amperes. This course, however, failed to
lead to the production of piperidine, as was just now observed; the proposed
method having proved ineffective in spite of all the experiments that have been
most carefully and searchingly conducted in many different quarters.
Now this failure notwithstanding, a considerable amount of labour has been
devoted to the object of ascertaining the cause of the suggested process thus
remaining inoperative, and it has been demonstrated by numerous tests that in
point of fact the successful production of piperidine from pyridine by electrolysis.
was feasible, provided three main conditions were accurately fulfilled.
What was shown by the results of the trials made was that (1) the quantity
of acid to be employed, (2) the selection of the electrodes, and (3) the degree of
purity of the acids and other substances required for the performance of the
operation, were so many points which required particular attention.
It was found, for instance, that no piperidine would form where the quantity*
of sulphuric acid was too small; and that on the other hand a more liberal
return of that compound was yielded in proportion as the amount of acid used
was greater, assuming that the other requisite conditions (hereinafter specified)
had been duly complied with;-that e.g. where 1 equivalent of pyridine was
used for every 1 equivalent of sulphuric acid, there would form no piperidine
at all; whereas a very fair percentage of piperidine was obtainable by the.
employment of 4 or more equivalents of acid to every 1 equivalent of pyridine;
and it was further observed that the use of too small amounts of acid resulted
in the formation of a brown body. Thus the conclusion was arrived at that
in order to ensure both a successful issue of the reaction and an adequate supply
of the final product it was necessary so to determine the proportion of acid
utilized that there should be present a sufficient surplus of acid during the
whole time occupied by the passage of the current.
Besides, while sulphuric acid solutions of pyridine have indeed to be con-
sidered, in practice, and are calculated to prove serviceable for purposes of
reduction, other acids also (such as hydrochloric acid, for example) have been

page_text: found by experiment to yield piperidine, if the same conditions that have
already been referred to, and that it was the object of the present invention to
determine, be duly observed.
Again, the trials above mentioned have led to the discovery that contrarily
to the suggestion to which reference is made in the introductory part of this
specification any desired insoluble material was not suited to the formation
of the anodes, in view of the fact that many an insoluble substance was
In
not at all incapable of affecting the course of the reaction more or less.
those cases, for example, where both the cathodes and anodes were formed of lead,
the supply of piperidine yielded, proved quite unexceptionable, whereas, with
a platinum anode and a lead cathode, the yield was simply nil. Also, it was
observed that, besides lead, carbon might be used in the construction of an
effective anode; though carbon certainly has the drawback of being very liable
to rapid wear. Soluble metals, of course, need not be considered at all in
connection with anodes; but even platinum, which is insoluble, will, if employed
as an anode, prevent any formation of piperidine.
Lead and carbon have been found by experiment to be serviceable materials
for the formation of cathodes, preference being due to the former metal. The
action of mercury is injurious, that of silver even more so, while platinum, 1
copper, iron and other metals will produce no piperidine, or, at best, mere
traces thereof.
In accordance with this invention, therefore, it is a desideratum of paramount
importance that lead should be made use of in the construction of the electrodes
.e. both the anodes and the cathodes-the substitution of carbon for lead
being permissible, though not conducive to quite as good results. Enquiry
has, furthermore, elicited the fact that where the purity of the acid used-or
of such other materials as may happen to be adopted (say in preparing the
diaphragms) is impaired by admixtures of copper, iron or the like, the
necessary reaction is interfered with or altogether hindered from taking place;
the injurious effect becoming the more marked, the greater the percentage of
the metals present. Thus even an inconsiderable amount of iron will reduce
the yield very materially, while a small proportion of copper vitriol (sulphate of
copper) will suffice entirely to prevent any formation of piperidine.
Hence according to this invention the process of manufacture of piperidine
mentioned in the introduction should undergo the following modifications: the
quantity of acid should be considerably increased, so that, as long as current
continues to be sent through the solution, an adequate excess of acid shall be
present a suitable proportion being 4 (or more) equivalents of acid to each
equivalent of pyridine. To this end, lead electrodes should be used, though, if
desired, carbon may be substituted for the lead. For the cathodes mercury
and silver might be employed, but the result will be not nearly as favourable
as where lead and carbon are utilized. And lastly the presence of such metal
compounds as are apt to affect the purity of the acid, or of other substances
that may have to be used,-admixture of copper or iron, for example,-should
as far as practicable be avoided.
If, under these conditions, pyridine be subjected to electrolytic reduction, a
very fair supply of piperidine will be gained.
Thus, assuming that sulphuric acid is used, the mode of procedure in the
preparation of piperidine would be somewhat as follows:
10 kilogrammes of pyridine should be dissolved in 110 kilogrammes of water
and 25 kilogrammes of sulphuric acid of 66° Be., the electrodes used being lead
and the electrolysis being performed with current of medium force; the whole
operation being conducted under the conditions just named.
Hitherto, where piperidine was obtained by reduction, sodium in an alcoholic
solution has been used. By adhering to the above conditions, however, in the
electrolytic reduction of pyridine, the advantage gained is greater simplicity and
economy in addition to which the whole process may under these conditions

page_text: be carried through in a smooth and reliable manner, as required for the practical
purposes of the trade.
Diaphragms may be dispensed with, though, generally speaking, their employ-
ment is to be recommended. The advantage arising from the use of diaphragms
is that they enable a colourless solution to be obtained, whereas in the absence
of a diaphragm the solution becomes tinged by a brown substance and acquires
a smell of acetic acid and butyric acid. From this circumstance, the use of a
diaphragm would appear to be desirable for certain special purposes, in those
cases, for example, where the product obtained is intended for immediate use.
In regard to the formation of piperidine as such, however, it is immaterial
whether diaphragms are used or not.
Very similarly to piperidine, dihydroquinoline may be produced in accordance
with this invention by substituting quinoline for the pyridine.
Dated this 19th day of October 1808
HASELTINE, LAKE & Co.,
45, Southampton Buildings, London, W.C., Agents for the Applicant.
A Process for the Preparation of Piperidine and Dihydroquinoline.
I, WILHELM PIP, of 61 Karlstrasse, Darmstadt, in the Empire of Germany,
Doctor of Philosophy, do hereby declare the nature of this invention and in
what manner the same is to be performed, to be particularly described and
ascertained in and by the following statement:-
It has before now been attempted to obtain piperidine from pyridine by
electrolysis; yet the attempts made in this direction have proved unavailing,
although a clear and definite course of action was indicated for the purpose of
making them successful. The method recommended was as follows:-10 parts
by weight of pyridine was to be dissolved in 100 parts by weight of sulphuric
acid at 10 per cent., and the resulting solution to be submitted to the action of
an electrical current; it being proposed to employ lead plates for cathodes, whilst
forming the anodes of any insoluble material; and the force of the current to
be used being set down at D100 = 12 amperes. This course, however, failed to
lead to the production of piperidine, as was just now observed; the proposed
method having proved ineffectual in spite of all the experiments that have been
most carefully and searchingly conducted in many different quarters.
Now this failure notwithstanding, a considerable amount of labour has been
devoted to the object of ascertaining the cause of the suggested process thus
remaining inoperative, and it has been demonstrated by numerous tests that in
point of fact the successful production of piperidine from pyridine by electrolysis
was feasible, provided three main conditions were accurately fulfilled.
What was shown by the results of the trials made was, that (1) the quantity
of acid to be employed, (2) the selection of the electrodes, and (3) the degree of
purity of the acids and other substances required for the performance of the
operation, were so many points which required particular attention.
It was found, for instance, that no piperidine would form where the quantity
of sulphuric acid was too small; and that on the other hand a more liberal
return of that compound was yielded in proportion as the amount of acid used
was greater, assuming that the other requisite conditions (hereinafter specified)
had been duly complied with; that e.g. where 1 equivalent of pyridine was
used for every 1 equivalent of sulphuric acid, there would form no piperidine
at all; whereas a very fair percentage of piperidine was obtainable by the

page_text: employment of 4 or more equivalents of acid to every 1 equivalent of pyridine;"
and it was further observed that the use of too small amounts of acid resulted
in the formation of a brown body. Thus the conclusion was arrived at that
in order to ensure both a successful issue of the reaction and an adequate supply
of the final product it was necessary to determine the proportion of acid
utilized that there should be present a sufficient surplus of acid during the
whole time occupied by the passage of the current.
Besides, while sulphuric acid solutions of pyridine have indeed to be con-
sidered, in practice, and are calculated to prove serviceable for purposes of
reduction, other acids also (such as hydrochloric acid, for example) have been
found by experiment to yield piperidine, if the same conditions that have
already been referred to, and that it was the object of the present invention to
determine, be duly observed.
Again, the trials above mentioned have led to the discovery that contrarily
to the suggestion to which reference is made in the introductory part of this
specification any desired insoluble material was not suited to the formation
of the anodes, in view of the fact that many an insoluble substance was
not at all incapable of affecting the course of the reaction more or less. In
those cases, for example, where both the cathodes and anodes were formed of lead,
the supply of piperidine yielded, proved quite unexceptionable, whereas, with
a platinum anode and a lead cathode, the yield was simply nil. Also, it was
observed that, besides lead, carbon might be used in the construction of an
effective anode; though carbon certainly has the drawback of being very liable
to rapid wear. Soluble metals, of course, need not be considered at all in
connection with anodes; but even platinum, which is insoluble, will, if employed
as an anode, prevent any formation of piperidine.
Lead and carbon have been found by experiment to be serviceable materials
for the formation of cathodes, preference being due to the former metal. The
action of mercury is injurious, that of silver even more so, while platinum;
copper, iron and other metals will produce no piperidine, or, at best, mere
traces thereof.
In accordance with this invention, therefore, it is a desideratum of paramount
importance that lead should be made use of in the construction of the electrodes
i.e. both the anodes and the cathodes the substitution of carbon for lead
being permissible, though not conducive to quite as good results. Enquiry
has, furthermore, elicited the fact that where the purity of the acids used-or
of such other materials as may happen to be adopted (say in preparing the
or the like, he
diaphragms)--is impaired by admixtures of copper, iron
necessary reaction is interfered with or altogether hindered from taking place:
the injurious effect becoming the more marked, the greater the percentage of
the metals present. Thus even an inconsiderable amount of iron will reduce
the yield very materially, while a small proportion of copper vitriol (sulphate of
copper) will suffice entirely to prevent any formation of piperidine.
Hence according to this invention the process of manufacture of piperidine
mentioned in the introduction should undergo the following modifications: the
quantity of acid should be considerably increased, so that, as long as current
continues to be sent through the solution, an adequate excess of acid shall be
present a suitable proportion being (or more) equivalents of acid to each
equivalent of pyridine. To this end, lead electrodes should be used, though, if
desired, carbon may be substituted for the lead. For the cathodes mercury
and silver might be employed, but the result, will not be nearly as favourable
as where lead and carbon are utilized. And lastly the presence of such metal
compounds as are apt to affect the purity of the acid, or of other substances
that may have to be used,-admixtures of copper or iron, for example, should
as far as practicable be avoided.
If, under these conditions, pyridine be subjected to electrolytic reduction, a
very fair supply of piperidine will be gained.

page_text: Thus, assuming that sulphuric acid is used, the mode of procedure in the
preparation of piperidine would be somewhat as follows:
10 kilogrammes of pyridine should be dissolved in 110 kilogrammes of water
and 25 kilogrammes of sulphuric acid of 66° Be., the electrodes used being lead
and the electrolysis being performed with current of medium force; the whole
operation being conducted under the conditions just named.
In both cases the density of current may be 4 to 5 amperes per square deci-
metre of the cathodic surface, but such density to be employed may also be
chosen higher or lower without any disadvantage.
Hitherto, where piperidine was obtained by reduction, sodium in an alcoholic
solution has been used. By adhering to the above conditions, however, in the
electrolytic reduction of pyridine, the advantage gained is greater simplicity and
economy; in addition to which the whole process may under these conditions
be carried through in a smooth and reliable manner, as required for the practical
purposes of the trade.
Diaphragms may be dispensed with, though, generally speaking, their employ-
ment is to be recommended. The advantage arising from the use of diaphragms
is that they enable a colourless solution to be obtained, whereas in the absence
of a diaphragm the solution becomes tinged by a brown substance and acquires
a smell of acetic acid and butyric acid. From this circumstance, the use of a
diaphragm would appear to be desirable for certain special purposes, in those
cases, for example, where the product obtained is intended for immediate use.
In regard to the formation of piperidine as such, however, it is immaterial
whether diaphragms are used or not.
Very similarly to piperidine, dihydroquinoline may be produced in accordance
with this invention by substituting quinoline for the pyridine.
Having now particularly described and ascertained the nature of my said
invention and in what manner the same is to be performed, I declare that what
I claim is:-
In the preparation of piperidine or of dihydroquinoline from pyridine or
quinoline (as the case may be) by electrolytic reduction in an acid solution, the
employment of a considerable excess of acid and of lead electrodes; it being
feasible if desired, to substitute carbon for lead, while in forming the cathodes
mercury or silver may be used instead of lead; also, the employment of an
acid, being as far as practicable free from salts of metals, and, generally, of
materials or substances (for diaphragms for example), as free as possible from
any metal compounds, with the object of rendering the production of piperidine
or of dihydroquinoline (as the case may be) possible, and of increasing the
"yield" in either of these products by compliance with the conditions above
stated,
HASELTINE, LAKE & Co.,
45, Southampton Buildings, London, W.C., Agents for the Applicant.