CA1036619A - Process for optical resolution of racemic lysine sulphanilate - Google Patents
Process for optical resolution of racemic lysine sulphanilateInfo
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- CA1036619A CA1036619A CA199,474A CA199474A CA1036619A CA 1036619 A CA1036619 A CA 1036619A CA 199474 A CA199474 A CA 199474A CA 1036619 A CA1036619 A CA 1036619A
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- Prior art keywords
- lysine
- solution
- sulphanilate
- racemic
- sulpha
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Abstract
ABSTRACT OF THE DISCLOSURE
Optical resolution of lysine in the form of racemic lysine sulphanilate is enhanced by the addition to the supersaturated solution of racemic lysine sul-phanilate of one or more substances which suppress the formation of seeds of racemic lysine sulphanilate in the supersatured solution. Among the seed-suppressing substances which may be added are lysine, lysine acetate, lysine carbonate, amino acetic acid and glycerol. The yield of optically active lysine sulphanilate is improved according to the disclosed process.
Optical resolution of lysine in the form of racemic lysine sulphanilate is enhanced by the addition to the supersaturated solution of racemic lysine sul-phanilate of one or more substances which suppress the formation of seeds of racemic lysine sulphanilate in the supersatured solution. Among the seed-suppressing substances which may be added are lysine, lysine acetate, lysine carbonate, amino acetic acid and glycerol. The yield of optically active lysine sulphanilate is improved according to the disclosed process.
Description
2596 '~
~Q366~9 ~: :
The invention rela.tes to a. process for optica.l .
resolution of ra.cemic lysine sulpha.nila.te.It is known (see British Patent Specifica.tions 1 ,191 ,100 and 1,250,557) tha.t ~ .
ra.cemic lysine sulphanilate ca.n be resolved optica.lly by ;: .~.:
5 subjecting a supersatura.ted solution of ra.cemic lysine :. ~
sulphanila.te to selective crystalliza.tion and by sepa.ra.ting ; ~.
the optically active lysine sulpha.nila.te, which ha.s then : .:
crystallized out, from the mother liquor. From the L-lysine ..
sulpha.nilate so obtained L-lysine, as such or in the form of a.
customary L-lysine compound, can be recovered, which ma.y be applied for enrichment of huma.n a.nd anima.l food. ~:
The use of sulphanilic acid as a.n a.uxilia.ry acid for :~.
optica.l resolution of ra.cemic lysine ha.s the adva.ntage, in compa.rison with use of an optica.lly a.ctive auxiliary a.cid, tha.t it ca.nnot become ra.cemized during the va.rious trea.tments.
' A disadva.ntage of the use of sulpha.nilic a.cid for optica.1 . resolution of ra.cemic lysine is tha.t the yield of optica.lly .
., active lysine sulphanila.te in the selective crysta.lliza.tion is -j sma.11, so tha.t a. la.rger recirculation is necessa.ry tha.n would ~. .
be with the use of a.n optica.lly a.ctive acid, for insta.nce optically a.ctive a.lpha-phenoxypropion-Lc a.cid, in which t.he , . required diastereoi~mer-sa.lt ca.n be sepa.ra.ted off with a. very .~ sa.tisfa.ctory yield through fra.ctiona.l crysta.llization. ~:
It ha.s been found tha.t there are substa.nces which, when dissolved in the supersaturated solution of ra.cemic lysine .:
' sulpha.nila.te, ca.n hinder the spontaneous formation of seeds of : racemic lysine sulpha.nilate in the supersa.turated solution, so ~ tha.t a grea.ter supersatura.tion rna.y be a.pplied a.nd hence a ; substa.ntially higher yield obta.ined of selectively crystallized ~0 optica.lly active lysine sulpha.nilate with a. high optica.l purity.
: ''.
~ ', ~ ~, ~, .
, .
.. ., ~. ... , - .. ~ , . ... .
~0366~9 Examples of substances which hinder the spontaneous seed formation are lysine, lysine acetate, lysine carbonate, amino acetic acid and glycerol.
Accordingly the present invention provides a process for optical resolution of racemic lysine sulphanilate by subjecting a solution containing supersaturated racemic lysine sulphanilate to selective crystallization and separating the lysine sulphanilate crystallized out from the mother liquor, wherein for the selective crystallization step a supersaturated solution is used in which lysine, lysiw acetate, lysine carbonate amino acetic acid or glycerole is dissolved which hinders the spontaneous seed formation of racemic lysine sulphanilate.
For interference with said seed formation according to the invention, lysine, lysine acetate or lysine carbonate are particularly useful.
Lysine is a preferred compound as it is also the compound which is to be resolved optically through the resolution of racemic lysine sulphani- ;
; late.
The quantity of substance used for interference with the seed formation may be for instance from 0.01 to 2 g per g of dissolved lysine sulphanilate contained in the supersaturated starting solution. For practical purposes, from 0.05 to 1.5 g per g of dissolved lysine sulphanilate in the supersaturated starting solution may be used.
The supersaturated starting solution may be obtained in known manner for instance by cooling a solution, or by concentrating it by evaporation, in which solution the racemic lysine sulphanilate and the substance which hinders said seed formation have been dissolved. Water is a very satisfactory solvent, but also other solvents may be used, including a mixture of water and methanol, ethanol, propanol, acetone or butanone.
The selective crystallization may be effected by seeding into the supersaturated solution crystals of the optically active lysine sulphani-late to be crystallized out, or by passing the supersaturated solution over ~2 ~'' , , .
- . : - ..
.
` 10366~9 ~ ~
a fixed bed of the optically active lysine sulphanilate to be crystallized out. If the two antipodes of lysine sulphanilate are present in the super- ; :
saturated solution in unequal quantities, the antipode present in a larger quantity may also crystallize selectively through spontaneous crystallization.
However in these circumstances, .': ~, ~,'' `' .
.. ,~ , , .
',' ' ' , ~ ':
: - 3a - :~ ~
: B : ~
lQ366~9 the selective crystalliza.tion is prefera.bly brought a.bout by conta.cting the supersatura.ted solution with crystals of the antipode to be crysta.llized out.
Conventiona.l selective crysta.lliza.tion techniques ~ .
5 may be employed wherein various conditions, as the degree of -~ .
supersa.tura.tionJ the crysta.lliza.tion time, the crysta.lliza.tion -..
tempera.ture, the size a.nd the qua.ntity of the seed crysta.ls, ma.y be va.ried. For instance, the supersa.tura.ted solution ma.y be divided into two equa.l pa.rts and a. qua.ntity of L-a.ntipode ca.used to crysta.llize selectively out of the one pa.rt a.nd a.n equa.l qua.ntity of D-a.ntipode to crysta.llize selectively out of the other pa.rt, the two rema.ining mother liquors returned after mixing to the zone for prepa.ra.tion of the supersa.tura.ted sta.rting solution. It is also possible for a. quantity of the one a.ntipode to be crysta.llized selectively out of the super- :~
sa.tura.ted solution, for a. qua.ntity of the other a.ntipode to . be crysta.llized selectively out of the rema.inirlg mother liquor, and for the mother liquor then left behind to be used in the -- prepa.ra.tion of the supersa.tura.ted sta.rting solution. Another procedure is one in which the mot.her liquor left behind a.fter a.
qua.ntity of the one a.ntipode ha.s crysta.llized out selectively, is processed by ca.using sa.id rnot.her liquor to becolrle su.bstantially sa.tura.ted with ra.cemlc lysine sulp~a.nila.te, a qua.ntity of the other antipode t.hen being obta.ined in the solid sta.te.
The L-lysine sulpha.nila.te obta.ined a.ccording to the invention ma.y be split up into its components in various wa.ys, for insta.nce by pa.ssing a.n aqueous solution of the sa.lt over a wea.kly ba.sic ion excha.nger. The sulpha.nilic a.cid is then bound on the ion excha.nger whilst a. lysine solution is obta.ined as elua.te.
~0 Alterna.tively a.n a.queous solution of the optica.lly a.ctive lysine sulpha.nila.te may be pa.ssed over a strongly a.cid ion echa.nger in the N~I4 form. The lysine is then bound to the ion excha.nger a.nd :
:': ' , , ' . , - , ', :
, ~036619 ~ ~
may be washed out by means of dilute a.mmonia. water. :
The following Exa.mples of the invention a.re provided. -In the Examples, the resolution efficiency is defined a.s a x 1OO X 100 ~, in which a., c a.nd d respecively represent the obta.ined qua.ntity of L-lysine sulphanila.te, the qua.ntity of seed ma.teria.l a.nd the ;-... .
qua.ntity of L-lysine sulpha.nila.te in the sta.rting ma.teria.l, -~ .
expressed in gra.ms, a.nd b the optica.l purity, expressed in per cents.
.:: - i, :.....
... . . .
:,:
10 Example I -.
.
30 g of ra.cemic lysine sulpha.nila.te were dissolved by hea.ting in 45 g of an a.queous solution conta.ining 21.8 ~ by weight of DL-lysine, the clea.r solution becoming supersa.tura.ted : .
by cooling to 25 C. To the supersa.tura.ted solution 2,5 g of . 15 solid L-lysine sulpha.nila.te (crysta.l size sma.ller than 0,05 millimetre) were a.dded, and the suspension obta.ined then stirred at 25 C for 15 minutes. The L-lysine sulpha.nila.te which ha.d ..
crysta.llized out wa.s then sepa.ra.ted by filtra.tion from the mother ;..
. liquorJ washed on the filter with a.pproxima.tel.y 20 millilitres 20 of metha.nol, a.nd dried. 8.7 g of L-lysine sulp.ha.nila.te were , obta.ined.
'I , .
l For determina.tion of the optica.l purity of the L-lysine sulpha.nila.te obta.ined, the sa.lt wa.s converted into L-lysine `~ ~ :
. monohydrochloride, by dissolving the 8.7 g of L-lysine sulpha.nilat ;
in ~5 millilitres of wa.ter a.nd pa.ssing the resulting solution over:
a. column filled with a.bout 150 millilitres of a. strongly acid ion ~ :
excha.nger obta.ined under the Tra.de Ma.rk Dowex 50 in the NH4 form. .
The column wa.s reflushed with deminera.lized wa.ter until a.mmonium sulphanila.te wa.s no longer present in the elua.te. The lysine ~
. 30 bound to the ion cxchanger wa.s washed out with ~.5 N a.mmonia. .::
.~..
, , , , .,. ,. . : . ..
~?366~9 ~
wa.ter, and the eluate thus obtained concentrated by ~:
evapo.ration at a reduced pressure to remove the ammonia..
; The lysine solution so.obtained wa.s neutra.lized with the required qua.ntity of hydrochloride a.cid (1 mole per mole of : 5 lysine) a.nd then eva.porated until fully dry. -.
5 g of L-lysine monohydroc.hloride with a. specific rotation of~ D = ~ 27.2 (lysine concentra.tion = 10; 6 N HCl) ~ were obtained.
From this follows a.n optica.l purity for the L-lysine ,~
10 sulphanila.te obtained of 100 %. The resolution efficiency ~:~
was 41.4 %. ~:~
~ ' Exa.mple II
41 g of racemic lysine sulpha.nila.te were dissolved by . ~.. ;
hea.ting, in 50 g of a.queous DL-lysine solution (10 % by weight 15 of DL-lysine), the resulting clea.r solution becorr;ing super-saturated by cooling to 25 C. -5 g of solid L-lysine sulpha.nila.te (crystal size smaller than 0. o5 millimetre) were then a.dded a.nd the suspension obta.ined stirred a.t 25 C for 5 minutes. The L-lysine sulphanila.te which 20 ha.d crysta.llized out wa.s then filtered off a.nd washed on the : filter with a.bout 20 millilitres of rnethanol.
12 . 84 g of L-lysine sulpha.nila.te with a.n optica.l purity of 89.6 % (89.6 % by weight of L by the side of 10.4 ~ by weight of DL) a.re obta.ined. The resolution efficiency wa.s 32 ~.
'' 25 Compa.rative Experiment 50 g of ra.cemic lysine sulpha.nilate were dissolved by hea.ting, in 50 g of water, the resulting solution becoming supersa.tura.ted by cooling to 25 C. In this solution, a.s in the Exa.mples I and II, the ra.cemic lysine sulpha.nila.te concentra.tion ;: ~o wa.s (10 % by weight higher tha.n the ra.cemic lysine sulphanila.te ' ,, .
.. - 6 -,"
i `,' concentration in a satura.ted a.queous solution a.t 25 c, which a.mounts to 40 ~ by weight. SubsequentlyJ 4. 2 g of :
solid L-lysine sulpha.nila.te (crysta.l size smaller than o, o5 millimetre) were a.dded a.nd the suspension obta.ined 5 stirred at 25 c for 5 minutes. The L-lysine sulpha.nila.te which had crysta.llized out was tllen filtered off a.nd wa.shed .. -. ~ ..,- . ....
on the filter with a.pproxima.tely 20 millilitres of metha.nol. .-~
16.5 g of L-lysine sulphanila.te having a.n optica.l purity of ~.8 ~ were obta.ined. The resolution efficiency ~:
wa.s 12 %.
`'.',.'' ' Exa.mple III :~ :
7.8 g of ra.cemic lysi.ne sulphanila.te were dissolved by heating in a. mixture of 45 g of wa.ter a.nd 5 g of ra.cemic lysine a.ceta.te, a.nd the clea.r solution thus obta.ined cooled ; ~.
15 to 25 c . 2. 5 g of solid L-lysine sulpha.nila.te (crysta.l size .
smaller than 0. o5 millimetre) were then a.dded a.nd the ..
suspension obta.ined stirred rOr 1 o minutes a.t 25 C .
The L-lysine sulpha.nila.te which ha.d crysta.llized :
out was filtered off a.nd wa.shed on the filter with a.bout 20 20 millilitres of met.ha.nol.
; 11.82 ~ of L-lysine ;ulp.ha.rli:La.te ha.ving a.n optica.l purity of 85.8 ~ were obtained. The resolution ef~iciency .
was 39. 2 ~.
,. ' " ', Exa.mple IV
~5 g of ra.cemic lysine sulL~ha.nila.te were dissolved by heating in a. mixture of 3~.1 g of wa.ter a.nd 1.9 g of ~ .
: glycerol, the clear solution becorning supersa.tura.ted by cooling to 25 C. 2 g of solid L-lysine sulpha.nila.te ~crysta.l size smaller tha.n 0.05 millirnetre) were then a.dded a.nd the ~0 resulting suspension stirred for 15 minutes a.t 25 C. The L-lysine :~ ' lQ36619 sulphanilate which ha.d crysta.llized out was then filtered off and washed on the filter with a.pproximately 20 millilitres of methanol.
9.28 g of L-lysine sulpha.nila.te ha.ving a.n optical 5 purity of 85 % were obta.ined. The resolution efficiency was 33.7 %-.
Example V
35 g of ra.cemic lysine sulpha.nilate were ~ssolved by hea.ting in a mixture of 39.15 g of wa.ter a.nd 4.35 g of amino a.cetic acid, the clear solution becoming supersa.turated by cooling to 25 C. 2 g of solid L-lysine sulpha.nila.te ~:`
(crystal size smaller tha.n 0. 05 millimetre) were then a.dded a.nd the resulting suspension stirred for 10 minutes a.t 25 C. The L-lysine sulphanila.te which ha.d crystallized out 5 was then filtered off a.nd washed on the filter with a.bout 20 millilitres of metha.no~.
7.88 g of optically pure L-lysine sulpha.nila.te were obtained. The resolution efficiency wa.s 33.6 ~.
Example VI
44 g of racemic lysine sulpha.nila.te were dissolved by heating in 56 g cf a.queous DL-lysine ca.rbona.te solution (10 % by weight of DL-lysine ca.rbona.te)) the resulting clea.r solution becoming supersa.turated by cooling to 25 C. 5.o g of solid L-lysine sulphanila.te (crysta.l size sma.ller tha.n 25 o. o5 millimetre) were then a.dded and the resulting suspension stirred for 5 minutes at 25 C.
: The L-lysine sulpha.nila.te which ha.d crysta.llized out wa.s then filtered off a.nd wa.shed on the filter with a.pproxi-mately 20 millilitres of metha.nol.
13. l g of L-lysine sulpha.nilate ha.ving a.n optica.l ;purity of 92.6 % were obta.ined. The resolution efficiency wa.s 32.4 ; - 8 - :
~ ." .
~Q366~9 ~: :
The invention rela.tes to a. process for optica.l .
resolution of ra.cemic lysine sulpha.nila.te.It is known (see British Patent Specifica.tions 1 ,191 ,100 and 1,250,557) tha.t ~ .
ra.cemic lysine sulphanilate ca.n be resolved optica.lly by ;: .~.:
5 subjecting a supersatura.ted solution of ra.cemic lysine :. ~
sulphanila.te to selective crystalliza.tion and by sepa.ra.ting ; ~.
the optically active lysine sulpha.nila.te, which ha.s then : .:
crystallized out, from the mother liquor. From the L-lysine ..
sulpha.nilate so obtained L-lysine, as such or in the form of a.
customary L-lysine compound, can be recovered, which ma.y be applied for enrichment of huma.n a.nd anima.l food. ~:
The use of sulphanilic acid as a.n a.uxilia.ry acid for :~.
optica.l resolution of ra.cemic lysine ha.s the adva.ntage, in compa.rison with use of an optica.lly a.ctive auxiliary a.cid, tha.t it ca.nnot become ra.cemized during the va.rious trea.tments.
' A disadva.ntage of the use of sulpha.nilic a.cid for optica.1 . resolution of ra.cemic lysine is tha.t the yield of optica.lly .
., active lysine sulphanila.te in the selective crysta.lliza.tion is -j sma.11, so tha.t a. la.rger recirculation is necessa.ry tha.n would ~. .
be with the use of a.n optica.lly a.ctive acid, for insta.nce optically a.ctive a.lpha-phenoxypropion-Lc a.cid, in which t.he , . required diastereoi~mer-sa.lt ca.n be sepa.ra.ted off with a. very .~ sa.tisfa.ctory yield through fra.ctiona.l crysta.llization. ~:
It ha.s been found tha.t there are substa.nces which, when dissolved in the supersaturated solution of ra.cemic lysine .:
' sulpha.nila.te, ca.n hinder the spontaneous formation of seeds of : racemic lysine sulpha.nilate in the supersa.turated solution, so ~ tha.t a grea.ter supersatura.tion rna.y be a.pplied a.nd hence a ; substa.ntially higher yield obta.ined of selectively crystallized ~0 optica.lly active lysine sulpha.nilate with a. high optica.l purity.
: ''.
~ ', ~ ~, ~, .
, .
.. ., ~. ... , - .. ~ , . ... .
~0366~9 Examples of substances which hinder the spontaneous seed formation are lysine, lysine acetate, lysine carbonate, amino acetic acid and glycerol.
Accordingly the present invention provides a process for optical resolution of racemic lysine sulphanilate by subjecting a solution containing supersaturated racemic lysine sulphanilate to selective crystallization and separating the lysine sulphanilate crystallized out from the mother liquor, wherein for the selective crystallization step a supersaturated solution is used in which lysine, lysiw acetate, lysine carbonate amino acetic acid or glycerole is dissolved which hinders the spontaneous seed formation of racemic lysine sulphanilate.
For interference with said seed formation according to the invention, lysine, lysine acetate or lysine carbonate are particularly useful.
Lysine is a preferred compound as it is also the compound which is to be resolved optically through the resolution of racemic lysine sulphani- ;
; late.
The quantity of substance used for interference with the seed formation may be for instance from 0.01 to 2 g per g of dissolved lysine sulphanilate contained in the supersaturated starting solution. For practical purposes, from 0.05 to 1.5 g per g of dissolved lysine sulphanilate in the supersaturated starting solution may be used.
The supersaturated starting solution may be obtained in known manner for instance by cooling a solution, or by concentrating it by evaporation, in which solution the racemic lysine sulphanilate and the substance which hinders said seed formation have been dissolved. Water is a very satisfactory solvent, but also other solvents may be used, including a mixture of water and methanol, ethanol, propanol, acetone or butanone.
The selective crystallization may be effected by seeding into the supersaturated solution crystals of the optically active lysine sulphani-late to be crystallized out, or by passing the supersaturated solution over ~2 ~'' , , .
- . : - ..
.
` 10366~9 ~ ~
a fixed bed of the optically active lysine sulphanilate to be crystallized out. If the two antipodes of lysine sulphanilate are present in the super- ; :
saturated solution in unequal quantities, the antipode present in a larger quantity may also crystallize selectively through spontaneous crystallization.
However in these circumstances, .': ~, ~,'' `' .
.. ,~ , , .
',' ' ' , ~ ':
: - 3a - :~ ~
: B : ~
lQ366~9 the selective crystalliza.tion is prefera.bly brought a.bout by conta.cting the supersatura.ted solution with crystals of the antipode to be crysta.llized out.
Conventiona.l selective crysta.lliza.tion techniques ~ .
5 may be employed wherein various conditions, as the degree of -~ .
supersa.tura.tionJ the crysta.lliza.tion time, the crysta.lliza.tion -..
tempera.ture, the size a.nd the qua.ntity of the seed crysta.ls, ma.y be va.ried. For instance, the supersa.tura.ted solution ma.y be divided into two equa.l pa.rts and a. qua.ntity of L-a.ntipode ca.used to crysta.llize selectively out of the one pa.rt a.nd a.n equa.l qua.ntity of D-a.ntipode to crysta.llize selectively out of the other pa.rt, the two rema.ining mother liquors returned after mixing to the zone for prepa.ra.tion of the supersa.tura.ted sta.rting solution. It is also possible for a. quantity of the one a.ntipode to be crysta.llized selectively out of the super- :~
sa.tura.ted solution, for a. qua.ntity of the other a.ntipode to . be crysta.llized selectively out of the rema.inirlg mother liquor, and for the mother liquor then left behind to be used in the -- prepa.ra.tion of the supersa.tura.ted sta.rting solution. Another procedure is one in which the mot.her liquor left behind a.fter a.
qua.ntity of the one a.ntipode ha.s crysta.llized out selectively, is processed by ca.using sa.id rnot.her liquor to becolrle su.bstantially sa.tura.ted with ra.cemlc lysine sulp~a.nila.te, a qua.ntity of the other antipode t.hen being obta.ined in the solid sta.te.
The L-lysine sulpha.nila.te obta.ined a.ccording to the invention ma.y be split up into its components in various wa.ys, for insta.nce by pa.ssing a.n aqueous solution of the sa.lt over a wea.kly ba.sic ion excha.nger. The sulpha.nilic a.cid is then bound on the ion excha.nger whilst a. lysine solution is obta.ined as elua.te.
~0 Alterna.tively a.n a.queous solution of the optica.lly a.ctive lysine sulpha.nila.te may be pa.ssed over a strongly a.cid ion echa.nger in the N~I4 form. The lysine is then bound to the ion excha.nger a.nd :
:': ' , , ' . , - , ', :
, ~036619 ~ ~
may be washed out by means of dilute a.mmonia. water. :
The following Exa.mples of the invention a.re provided. -In the Examples, the resolution efficiency is defined a.s a x 1OO X 100 ~, in which a., c a.nd d respecively represent the obta.ined qua.ntity of L-lysine sulphanila.te, the qua.ntity of seed ma.teria.l a.nd the ;-... .
qua.ntity of L-lysine sulpha.nila.te in the sta.rting ma.teria.l, -~ .
expressed in gra.ms, a.nd b the optica.l purity, expressed in per cents.
.:: - i, :.....
... . . .
:,:
10 Example I -.
.
30 g of ra.cemic lysine sulpha.nila.te were dissolved by hea.ting in 45 g of an a.queous solution conta.ining 21.8 ~ by weight of DL-lysine, the clea.r solution becoming supersa.tura.ted : .
by cooling to 25 C. To the supersa.tura.ted solution 2,5 g of . 15 solid L-lysine sulpha.nila.te (crysta.l size sma.ller than 0,05 millimetre) were a.dded, and the suspension obta.ined then stirred at 25 C for 15 minutes. The L-lysine sulpha.nila.te which ha.d ..
crysta.llized out wa.s then sepa.ra.ted by filtra.tion from the mother ;..
. liquorJ washed on the filter with a.pproxima.tel.y 20 millilitres 20 of metha.nol, a.nd dried. 8.7 g of L-lysine sulp.ha.nila.te were , obta.ined.
'I , .
l For determina.tion of the optica.l purity of the L-lysine sulpha.nila.te obta.ined, the sa.lt wa.s converted into L-lysine `~ ~ :
. monohydrochloride, by dissolving the 8.7 g of L-lysine sulpha.nilat ;
in ~5 millilitres of wa.ter a.nd pa.ssing the resulting solution over:
a. column filled with a.bout 150 millilitres of a. strongly acid ion ~ :
excha.nger obta.ined under the Tra.de Ma.rk Dowex 50 in the NH4 form. .
The column wa.s reflushed with deminera.lized wa.ter until a.mmonium sulphanila.te wa.s no longer present in the elua.te. The lysine ~
. 30 bound to the ion cxchanger wa.s washed out with ~.5 N a.mmonia. .::
.~..
, , , , .,. ,. . : . ..
~?366~9 ~
wa.ter, and the eluate thus obtained concentrated by ~:
evapo.ration at a reduced pressure to remove the ammonia..
; The lysine solution so.obtained wa.s neutra.lized with the required qua.ntity of hydrochloride a.cid (1 mole per mole of : 5 lysine) a.nd then eva.porated until fully dry. -.
5 g of L-lysine monohydroc.hloride with a. specific rotation of~ D = ~ 27.2 (lysine concentra.tion = 10; 6 N HCl) ~ were obtained.
From this follows a.n optica.l purity for the L-lysine ,~
10 sulphanila.te obtained of 100 %. The resolution efficiency ~:~
was 41.4 %. ~:~
~ ' Exa.mple II
41 g of racemic lysine sulpha.nila.te were dissolved by . ~.. ;
hea.ting, in 50 g of a.queous DL-lysine solution (10 % by weight 15 of DL-lysine), the resulting clea.r solution becorr;ing super-saturated by cooling to 25 C. -5 g of solid L-lysine sulpha.nila.te (crystal size smaller than 0. o5 millimetre) were then a.dded a.nd the suspension obta.ined stirred a.t 25 C for 5 minutes. The L-lysine sulphanila.te which 20 ha.d crysta.llized out wa.s then filtered off a.nd washed on the : filter with a.bout 20 millilitres of rnethanol.
12 . 84 g of L-lysine sulpha.nila.te with a.n optica.l purity of 89.6 % (89.6 % by weight of L by the side of 10.4 ~ by weight of DL) a.re obta.ined. The resolution efficiency wa.s 32 ~.
'' 25 Compa.rative Experiment 50 g of ra.cemic lysine sulpha.nilate were dissolved by hea.ting, in 50 g of water, the resulting solution becoming supersa.tura.ted by cooling to 25 C. In this solution, a.s in the Exa.mples I and II, the ra.cemic lysine sulpha.nila.te concentra.tion ;: ~o wa.s (10 % by weight higher tha.n the ra.cemic lysine sulphanila.te ' ,, .
.. - 6 -,"
i `,' concentration in a satura.ted a.queous solution a.t 25 c, which a.mounts to 40 ~ by weight. SubsequentlyJ 4. 2 g of :
solid L-lysine sulpha.nila.te (crysta.l size smaller than o, o5 millimetre) were a.dded a.nd the suspension obta.ined 5 stirred at 25 c for 5 minutes. The L-lysine sulpha.nila.te which had crysta.llized out was tllen filtered off a.nd wa.shed .. -. ~ ..,- . ....
on the filter with a.pproxima.tely 20 millilitres of metha.nol. .-~
16.5 g of L-lysine sulphanila.te having a.n optica.l purity of ~.8 ~ were obta.ined. The resolution efficiency ~:
wa.s 12 %.
`'.',.'' ' Exa.mple III :~ :
7.8 g of ra.cemic lysi.ne sulphanila.te were dissolved by heating in a. mixture of 45 g of wa.ter a.nd 5 g of ra.cemic lysine a.ceta.te, a.nd the clea.r solution thus obta.ined cooled ; ~.
15 to 25 c . 2. 5 g of solid L-lysine sulpha.nila.te (crysta.l size .
smaller than 0. o5 millimetre) were then a.dded a.nd the ..
suspension obta.ined stirred rOr 1 o minutes a.t 25 C .
The L-lysine sulpha.nila.te which ha.d crysta.llized :
out was filtered off a.nd wa.shed on the filter with a.bout 20 20 millilitres of met.ha.nol.
; 11.82 ~ of L-lysine ;ulp.ha.rli:La.te ha.ving a.n optica.l purity of 85.8 ~ were obtained. The resolution ef~iciency .
was 39. 2 ~.
,. ' " ', Exa.mple IV
~5 g of ra.cemic lysine sulL~ha.nila.te were dissolved by heating in a. mixture of 3~.1 g of wa.ter a.nd 1.9 g of ~ .
: glycerol, the clear solution becorning supersa.tura.ted by cooling to 25 C. 2 g of solid L-lysine sulpha.nila.te ~crysta.l size smaller tha.n 0.05 millirnetre) were then a.dded a.nd the ~0 resulting suspension stirred for 15 minutes a.t 25 C. The L-lysine :~ ' lQ36619 sulphanilate which ha.d crysta.llized out was then filtered off and washed on the filter with a.pproximately 20 millilitres of methanol.
9.28 g of L-lysine sulpha.nila.te ha.ving a.n optical 5 purity of 85 % were obta.ined. The resolution efficiency was 33.7 %-.
Example V
35 g of ra.cemic lysine sulpha.nilate were ~ssolved by hea.ting in a mixture of 39.15 g of wa.ter a.nd 4.35 g of amino a.cetic acid, the clear solution becoming supersa.turated by cooling to 25 C. 2 g of solid L-lysine sulpha.nila.te ~:`
(crystal size smaller tha.n 0. 05 millimetre) were then a.dded a.nd the resulting suspension stirred for 10 minutes a.t 25 C. The L-lysine sulphanila.te which ha.d crystallized out 5 was then filtered off a.nd washed on the filter with a.bout 20 millilitres of metha.no~.
7.88 g of optically pure L-lysine sulpha.nila.te were obtained. The resolution efficiency wa.s 33.6 ~.
Example VI
44 g of racemic lysine sulpha.nila.te were dissolved by heating in 56 g cf a.queous DL-lysine ca.rbona.te solution (10 % by weight of DL-lysine ca.rbona.te)) the resulting clea.r solution becoming supersa.turated by cooling to 25 C. 5.o g of solid L-lysine sulphanila.te (crysta.l size sma.ller tha.n 25 o. o5 millimetre) were then a.dded and the resulting suspension stirred for 5 minutes at 25 C.
: The L-lysine sulpha.nila.te which ha.d crysta.llized out wa.s then filtered off a.nd wa.shed on the filter with a.pproxi-mately 20 millilitres of metha.nol.
13. l g of L-lysine sulpha.nilate ha.ving a.n optica.l ;purity of 92.6 % were obta.ined. The resolution efficiency wa.s 32.4 ; - 8 - :
~ ." .
Claims (3)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for optical resolution of racemic lysine sulphanilate by subjecting a solution containing supersaturated racemic lysine sulphani-late to selective crystallization and separating the lysine sulphanilate crystallized out from the mother liquor, wherein for the selective crystalli-zation step a supersaturated solution is used in which lysine acetate, lysine carbonate amino acetic acid or glycerol is dissolved which hinders the spon-taneous seed formation of racemic lysine sulphanilate.
2. A process according to Claim 1, wherein the said substance is lysine.
3. A process according to Claim 1 or 2, wherein a supersaturated solution is used containing from 0.05 to 1.5 g of said substance to every g of dissolved lysine sulphanilate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA199,474A CA1036619A (en) | 1974-05-10 | 1974-05-10 | Process for optical resolution of racemic lysine sulphanilate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA199,474A CA1036619A (en) | 1974-05-10 | 1974-05-10 | Process for optical resolution of racemic lysine sulphanilate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1036619A true CA1036619A (en) | 1978-08-15 |
Family
ID=4099983
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA199,474A Expired CA1036619A (en) | 1974-05-10 | 1974-05-10 | Process for optical resolution of racemic lysine sulphanilate |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1036619A (en) |
-
1974
- 1974-05-10 CA CA199,474A patent/CA1036619A/en not_active Expired
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