DE1445149A1 - Process for the preparation of L-alpha-aminolactam from a mixture of D- and L-alpha-aminolactam - Google Patents

Description

DR. MÖLLER-BORE dipl.-ing. GRALFS

DIPL.-PHYS. DR. MANITZ DIPL.-CHEM. DR. DEUFEL PATENTANWÄLTE

June 27) 368

P 14 45 14.9.1 * Ho-S 686

STAHIGAHBON U.V., HUMiLlSN (the Netherlands)

Method of manufacture; by L-ct-Aininolac.tam from a mixture of D- and L-flt-aminolactam

The invention relates to the production of L-uC-.H.minolactam, from a Geraisch of D- and L-ct-iiminolactam, one of the optical antipodes in the form of the salt of the optically active pyrolidonecarboxylic acids of the same steric configuration in a liquid medium falls> separates the precipitate from the liquid, whereby a phase rich in L-ß-amine lactam and a phase rich in D- aminolactam is obtained, and then nolftctan is obtained from the first product of the L-Qfc- amine

"A connection of the same" teric configuration "" should be understood to mean a connection,

909804 / 129S- cT

BRAUNSCHWXrPvAK aOactftnuuc ■ 9 <os »ii a · 4» 7 · monchkn 22, robcrt-koch-itr. t 9 loam 2 »ei 10

<_ 2 -

which can be found in that of Cahn and Ingold in J "Chem" Soc. Pages 612 up to and including 622 (1951) described manner can be derived from the same optical isomer of glyceraldehyde. .

Furthermore, the salts of an L- <£ -aminolactam with L-, or -D-pyrrolidonecarboxylic acid-2, as "L, L-UaIz" _f or "L ₅ I) -SaIz" and those of a D-it- Aminolactams, with L- or ju-fyrrolidonecarboxylic acid-2 as "D ₁ Ir-. CaIz", or "u, X) -SaIz".

Like from HeIv. GMm. Acta, XLI (1958), pp. 181-188, L-ct-amino ^ -caprolactam can be prepared by adding equimolar amounts of D, La-Amj.no-caprolactam and L-pyrrolidonecarboxylic acid. 2, after dissolving in methanol, then that from the oil salt of L-aMmino - ^ - caprolactam and L-pyrrolidonecarboxylic acid-2. existing, precipitate separates from the mother liquor and in Lf ^ -TÄmino - ^ - ca.pro- ,. 3.aotaffl and L-PyrrQlidoncarbonsäure-2 splits ... The L-Eyrrolidon -? .. carbpn-säure-2 left in the mother liquor is separated by means of barium niethylate ..Ith.ßovm-. ■ des.-barium salt.es is precipitated. This salt “is filtered off

and converted back into L-pyrrolidonecarboxylic acid-2. The filtrate, which contains the l-ct-alino-caprolactam, is evaporated in the akuuni, and the residue is racemized by sodium. By Vakuumdetillation at 1βο - 19o ° 0 falls here rait an efficiency of o, the race- mix mixture j in. After adding a fresh Hen- ^ e D, L-it-Amino- £ -caprolactam, the latter is again subjected to the above-mentioned treatments. By constant repetition of this approach, we can finally make 70 .J of the original Henge I), L-

to convert into the L-li'orni.

In this process, l-ian uses a L-pyrrolidonecarboxylic acid-2, which is equivalent to the total amount of CL-umino-g-caprolactam, so that after the calcium has been taken in, a flow remains in which the D-cb-Aminu-g-caprolactara una the unprecipitated L-tt-amino-ε-caprolactam, both bound to an equivalent Henge L-Fyrroli'ioncarbonsäure-2, are dissolved, here the disadvantage is connected, that the L-pyrrolidonearboxylic acid-2 is to be separated from the cL-amino-g-caprolactam before the substance is racemized

BATH ORIGINAL

909804/1295

can. I; ieser ¹ J? Rermvor {- an _c ; moreover, it is quite expensive, since a portion of beer is required for metallic methylate. Finally, the L-pyrrolidonecarboxylic acid-2 must be separated from the barium salt again for reuse.

The Hacemi sie rungs wise, whereby J> 0% of the d-amino £ -caprolactam is lost, is a further disadvantage of this process.

A method has now been found which can remedy the above-mentioned disadvantages.

The process according to the invention for the preparation of La-aminolactam, wherein one of the optical atipodes in I ¹ OMi of the salt of the optically active pyrrolidonecarboxylic acid-2 of leicher steric configuration is precipitated from a mixture of D- and L-ifc-aminolactam in a liquid medium , separates the precipitate from the liquid, whereby a phase rich in L-OL-aminolactam and a phase rich in D-QHuniiiolactam is obtained, and the L-Cb-amino lactam is then obtained from the first product, which results in k ' ekemizeichnet that a lot of pyrrolidone carbon

original 90.9804 / 1295

acid is used, which yerin ^ er is called that

Kerr; e equivalent to the total amount & -aminolaotam, and a liquid medium; is used, in which the salts of D- and L-a-iirainolactn; ... with the optically active Pyrroliaoncarburis'!. uri: -2 form are practically insoluble.

The commonly used procedure for - .. ufspaltuno, · von J}, L-ucmischen ^ dur-ch ieaktion with a optically active connection is based on the uriaittlunt, -einer Combination of an optically active compound with a liquid in which the solubility of the diastereoisomers formed, i; enÜ4, -end are different, so that they can be separated by fractional crystallization. That oban known / experienced described forms an application of this principle.

According to the invention; the crystallization will blow away carried out in a hedium in which the Diastereoisomers are both insoluble. In one such a medium one would expect a precipitate, which consists of a mixture of the two diastereoscopic

909804/1295

Isomers existed and were in a ratio
which does not differ significantly from that in which D- and it-cir-ABiinolactani are present in the mixture to be divided, surprisingly has
however, it turned out that when using
a keii ^ ei ^ frrolidoncarboxylic acid, which r. * erin- ^ er or only a little; is greater than the length,
which is equivalent to the length of the optically active α-aminolactam of the same steric configuration, a repeat is obtained which
consists for the most part of the salt of these two compounds.

The optically active compound is optically active pyrrolidonecarboxylic acid-2 or the ammonium salt thereof, or a mixture of these two compounds . use.

As a liquid medium according to the invention, any Serve liquid in which the salts of «K-aminolactaas with the optically active pyrolidonecarboxylic acids are almost insoluble, while the ct-aminolactaa itself probably dissolves in this auxiliary liquid.

909804 / 129S

solves. Such liquids are e.g. B. dioxane and hydrocarbons such as gasoline, kerosene, hexane, heptane, benzene, toluene, xylene, toesitylene, cyclohexane and alkylcyclohexane.

According to one embodiment of the process according to the invention, the mixture of D- and L-cfc-ii is brought together with L-pyrrolidone-cax'-2-acid in the liquid Hediuni, whereby the L, L-ball is precipitated.

In order to achieve the best possible:, - uten separation between D- and L-ctr-aminolactam to ;; elanj.; En, it is recommended to a maximum of 1 Iiol, mostly 0.9 to 1 Ho 1 L-pyrrolidonecarboxylic acid-2 Use L-a-üminolactam su per haul .

The mixture of D- and L-cL-aminolactam can be brought into contact with the pyrrolidone carboxylic acid in the liquid medium in several ways. You can z. B. suspend the gures in a solution of Ii- and L- CLr aminolactam in this medium or

909804/1295

- ■ 8 -

a solution of D- and L-α-aminolactam in the a solution of the acid in a liquid medium Add polar solvents such as alcohol or water.

According to another embodiment of the invention Procedure is one of two reagents, dissolved in a polar solvent and this solution is gradually added to the liquid medium in which the other reagent is divided, while at the same time the polar solvent is excreted from the medium ..

however, han prefers both reagents in the same dissolve polar solvent, add this solution to the liquid medium and the polar solvent to be distilled off from the auxiliary liquid. It is beneficial to follow the polar solvent and afterwards to be added, and both the distilling and the adding of the same at the same rate perform.

909804/1295

1445U9

The polar solvent chosen is preferably a liquid that does not dissolve with the Mix the auxiliary liquid, these! '' Liquids can then be easily separated from each other in the distillate and then used again.

The L, L-SaIz can be found in it, J, L-Balz Be cleaned up by keeping it during some Zei ^ heated with a lot of L-et-aminolactam, which is the amount of the D-ct-aminolactam bound in the D, L-salt at least equals «This heating can take place in the medium used, in which dissolved the required amount of L-et-AminoIactarn is.

It tends to be that the equilibrium:

D, L-B * la Aminolactam

L ₁ L-SaIz + D-ct-

sicil left under the conditions to the right.

Bti Vejpwendung of a maximum of 1 mole of L-Pyrrolicloncarbon ·

80880A / 1295

- 1ο -

acid per mole of Ir-ft-iuninolactam, this noi _ia uri £ ,, · can be carried out in a simple manner by nail heating the courtship in the kedium in which it has formed, because the required key i-cfc-aminolactam is still present in it.

Preferably, however, the L ₁ L salt is separated from the liquid and dissolved in a polar solvent, whereupon the resulting solution, in the presence of an amount of It- <t-aminolactam, which corresponds to the amount of B-Cb bound _{in the .U 1 L-UaIz} Ariinolactam is at least equivalent, is brought into contact with a fresh amount of the liquid medium and the It ₉ Jr salt is precipitated again by excretion of the polar solvent.

Another, very * suitable cleaning process consists of extracting the Ir, L salt with an alcohol in which. the D _t L-SaIz can be loosened more easily than the LL-SaIz. Such alcohols are, for example, methanol, ethanol, isopropanol and butanol.

90980A / 1295

14 * 5149

If so desired, the Jj, L-Balz, before * this from the ^, L-SaIz _Ä ereini _r .t wii'd, be kept for some time in a fresh I "'en ^ e of the liquid heddium at boiling temperature so that it is freed from any occluded free et-aminolactam.

The Isutterlau ^ e, which remains after the LjL-LaIz has excreted from the mixture of α- and L-Cfc-Aminolacarn, behaves inert with respect to sodium. This makes it possible in a simple manner to remove the i) -GL-aminolactam present therein by heating the LOSUn ₁₃ ; to racemize with iSodium. Before, however, the -zu ;; sweise iiacemisierunj ,, · is carried out by passing the solution in the presence of a s ^{e c} i ⁿ ~ gen amount of dry Natriurahydroxyds is heated.

The L, L-salts become L-α-aminolactam and L-pyrrolidonecarboxylic acid-2 won. According to a particularly suitable method, an aqueous solution of the L, L salt via a cation exchanger, preferably via its ammonium form. Bas it aminolactam is adsorbed by the ion exchanger

■ · ORIGINAL BATHROOM

9098CU / 1295

beer, while the pyrrolidonecarboxylic acid as a aqueous solution of Ammoniuinpyrrolidonat from the Exits ion exchanger, leaves this solution free the pyrrolidonecarboxylic acid in a known manner, which then becomes a following JJ, L-terminations can be used. You can also get the solution use as such, possibly after evaporation, for this purpose. That of the ion exchanger adsorbed L-fiLrAminolactam is, preferably eluted with an aqueous ammonia solution.

This offers the advantage that when the ammonia evaporates from the fluid, a solution of the free L-cfc-iiminolactanis remains, while also the ion exchanger is returned to its original state *

The preferred option is to use as a cation exchanger sulfonated copolymers of divinylbenzene and styrene · However, other conventional cation exchangers can also be used at v / ends.

The advantages of the method according to the invention are obvious. In the first place it should be mentioned that the Procedure is less cumbersome and also saves

9.09804 / 1295

U45149

chemicals, because after the removal of the L, L salt from the liquid medium a solution remains that does not contain pyrrolidonecarboxylic acid, so that one is in the solution D-Ctr-aminolactam before racemization not from this connection needs to be disconnected. Second, this racemization can be much easier perform and achieve a much higher degree of efficiency.

According to another Ausführunisform of erfindun _t "sgewäf3en method, the mixture of D- and L-Qr aminolactam with D-pyrrolidone carboxylic acid is contacted in the liquid medium falls whereby the D, D-Saiz. This salt is split up into D-pyrrolidonecarboxylic acid, which is used again, and D-tfeminolactam, which is racemized. From the mother liquor z. B, the L-Qr aminolactam can be obtained by evaporation.

In order to achieve as complete a separation as possible of D- and L-Or-aminolactam, it is recommended mini"*! 1 mole of D-I ^ rrolidoncarbonicäure-2 per mole of D-flh

909804 / 129E

Amino lactam- to use. Preferred catfish are served an excess, up to 0.1 Hol.

invent _; -; sfoemäi.5e method is »I especially» suitable for the production of L-Or-Amino-g-caprolactam. For this purpose, the mixture of L- and ^ -ct-Äniino-fi-caprolactam with L-pyrrolidone- _γ carboxylic acid is preferably dissolved in water, whereupon this solution is gradually pumped to boiling toluene, but that sleeps L, L-oalz, while the water distills off azeotropically.

The L-it-amino- ^ - caorolactam is preferably prepared by a cycle process, an aqueous solution of l), L- <Wunino- ε -caprolaetam · and L-ammo- nxumpyrrolidonat, which 0.9 to 1 mol of ammonium pyrrolidone ' at ό «^ ol L-ct-amino - ^ - contains caprolactam, brought into toluene and the water is evaporated. The accruing «? Precipitation; is eliminated and precipitated again by this after dissolution in water, and Zülät'z 'an amount of L-dt-amino-6-caprolactimV * ⁰ which the amount available on the Wi'eäeriscnlag D-ct-amino- £, -capr6iactäni "at least the same thing ^{: is brought} into 'foluene, after which the water is

ÜAD OBIGlNAL

909 8047129 ^ "' ^: '

U45149

steams. Precipitation: vird dissolved again excreted and in water and this solution "over a Kationenaust & u _t cher" leads is that is pre-treated with an aqueous ammonia solution.. The solution of L-atamoniumpyrrolidonate emerging from the ion exchanger is possibly returned to the process after steaming in order to react again with i), L- <t-aniino- ^ - caprolactam. The on the ion exchanger adsorbed L £ - \ A.mino- £ -caprolactara is eluted with an aqueous Aminonioklösung, the ion exchanger ¹ which is regenerated and an aqueous Lösun _to L-ct-amino ^ capi'oladbaiiä obtained, of which a Part of the toluene, which has remained after the precipitate has separated out, is used to hacemize the D-ct-amino contained in it, also according to Üindarapfuns. Oaprolactams are heated to boiling with dry sodium hydroxide. The sodium hydroxide is then removed and the solution extracted with water, whereby an aqueous solution of DjL-it-Aatino-g-caprolÄctaii is obtained, which is returned to the FroxeB.

909804/1295

U45149

The invention is of particular importance for the production of L-ctrAmino - ^ - caprolactam, but can also be used for the production of L-ct-Asiinolactams with more or less carbon atoms in the -tiing, such as. B. L-Ot-AminoÖnantholactam and L-flhAminovalerolactam can be used.

The invention is not limited to the production of L-A-amino lactarn, but includes

at the same time that of D-it-aminolactam, which the former is analog.

example 1

218.3 g (1.7 Hol) D, L-flfr »Amino-ε-caprolactam is dissolved with 99.1 g ζο.77 mol) L-fyrrolidonecarboxylic acid-2 in 500 g water. This solution is pumped into 3 liters of boiling toluene in one hour at such a rate that as much water is distilled off per unit of time as is added. The heating is then continued for half an hour. Sarftuf since · Reaktionsg * - Xn Biiech filtered while hot and the precipitate by suction as completely as possible of "" ~ · *

9.09804 / 1295

- 17 -
.Liquid freed.

The precipitate is brought into 1.5 l of fresh toluene, by. is kept at boiling temperature for half an hour. After that, 3r filtered off and dried. This results in 196.9 g of salt, 95% of which consists of L, L salt (efficiency 99 »4- / <>, calculated with reference to the one used Pyrrolidone carboxylic acid) "

This salt is dissolved in 3 ° o g of water, the 1o, 1 g L-A-Aniino-f-caprolactam is added. This solution is pumped into 3 l of boiling toluene in one hour; the resulting precipitation is still during Heated for half an hour in boiling toluene, filtered off, and again in toluene until boiling heated, filtered off and dried, all in the manner described above. In this way 196.1 g of salt are obtained, of which 98.8 ^ L, L-salt.

909804/1296

1 * 45149

Example 2

The loluene fractions obtained according to Example 1, after the salt has been removed therefrom, are combined and evaporated to a volume of about 3 liters, whereby an about 5 percent by weight solution of df-amino - ^ - caprolactam is obtained, which mainly contains the .D - Contains shape. To this solution, 0.6 g (0.5% by weight based on the aminolactam) of dry sodium hydroxide is added, whereupon the mixture is kept at the boiling temperature for half an hour. Then the reaction mixture to remove the sodium 'hydroxide in a half hour is up to 90 ° G cooled and filtered. It turns out that the aminolactam is completely racerized, while no loss of tf-aaino-g-caprolactam was found.

Example 3

The salt prepared according to Example 1 was 6oo g Water dissolved, creating an approximately 25 percent by weight Solution of the üalae »accrued. This solution was at a temperature of 55 ° G with a room

speed = »1 over 55o ml of a" Dowex 5o " 909804/1295

Latiorienaufctauschers led in the ammonium form, which was then washed with water until no more pyrrolidonecarboxylic acid could be detected in the washing water. The ion exchanger was then also at 55 ° G, with 5 °° ⁿ 'l 5% aqueous iuumoniaklösuny; extracted and washed with water. The resulting solution contained an amount of ci-amino-i-caprolactain which was equivalent to that in the salt. The product consisted of £ 98.8 from the L -]? Onn,

- patent claims -

909804/1295

Claims (1)

Claims Process for the preparation of L-af-aminolactam from a mixture of I) - and L- «sC-aminolactam, one of the optical antipodes in the form of the salt or optically active pyrrolidonecarboxylic acid-2 falls of the same steric configuration in a liquid medium, the Precipitation separates from the liquid, creating an L-öt-aminolactam-rich and a B-.Z-aminolactam-rich Phase is obtained, and then from the first product the L-öf-aminolact "am wins, characterized that an amount of pyrrolidonecarboxylic acid is used which is less as the amount equivalent to the total amount--aminolactam, and a liquid medium is applied in which the salts of D- and L - # - aminolactam mit.der optically active pyrrolidonecarboxylic acid e-2 both practically insoluble 2. The method according to claim 1, characterized in that g e k e η η ζ e'i c h η e t that as a liquid medium a 9098CU / 129S Hydrocarbon is used. 3. The method according to claim 1 or 2, characterized in that the mixture of D- and L-ifc-aminolactam with L-pyrrolidonecarboxylic acid-2 is brought together in the liquid medium, the salt formed thereby separates from the liquid, from this salt the L-ct-aminolactam wins and, if necessary, directly racemizes the D-it-aminolactam with the resulting solution. 4. The method according to claim 3> characterized g e k e η η «• rejects that each Hol Ir- <4-aminolactan ■ ftxiaal 1 Hol L-pyrrolidonecarboxylic acid-2 is used · 5 × The method according to Anepruch 4, characterized in that per mole of L-tfrAninolactaa is 0.9 bia 1 Hol Ir Pyrrolidoncarboneäure-2 applied · BATH 90980A / 129B 6. The method according to any one of the preceding claims, characterized ge k β η η ζ ei c h η et that the ammonium salt of pyrrolidonecarboxylic acid-2 is applied 7. The method according to any one of the preceding claims, characterized in that g e c hn et, that the liquid medium is a solution of L-pyrrolidonecarboxylic acid-2 and from the mixture of D- and L-it-ainolactara in a polar solvent is added and at ^ -1 sooner that - polar solvents are removed from it. 8. The method according to claim 7> characterized in that a boiling solution of toluene a solution of L-pyrrolidonecarboxylic acid-2 and a mixture of D- and L-ci-amino- £ -caprolactam in water is added and to- ' the water is immediately distilled off azeotropically . - ■ - ■ '.- .. ■ .- - "■■" - "■' 9 · Method according to claims 1 to 1o, characterized marked that one that 909804/12 9t ^{c Λ} '' : ΐ ν * ί <"' i - 23 - L, L salt separates from the liquid medium, dissolves in a polar solvent, the resulting Solution, in the presence of a hexite L-iit-aminolactam, which of those found in the salts Henfje D-ÖC-Aminolactaiii at least equivalent is brought into contact with a fresh amount of the liquid medium and one by excretion of the polar solvent the L, L-salt falls. ' 1o. Method according to claims .1 to 1o, characterized in that the L, L — salt with methanol, ethanol, isopropanol or butanol is extracted. 11. The method according to claims 1 to 11, characterized in that an aqueous Solution of the L, L ~ salt is passed through a cation exchanger, which is in the ammonium form is located, whereupon this ion exchanger is treated with an aqueous ammonia solution. 909804/1295 12. The method according to claim 1 or 2, characterized in that .that the Mixture of D- and L-tf-AminoXaetam with D- Pyrolidonecarboxylic acids in the liquid Bringing the medium together, the salt formed thereby separates out of the liquid and out the resulting liquid phase wins the L lactam. 13 · The method according to claim 7> characterized in that per mole of D - <(- aminolactam a minimum of 1 mol of D-pyrrolidonecarboxylic acid-2 is used will. 14. The method according to claim 8, characterized in that per mole of D-et-aminolaetam 1.1 to 1 mol of 2-pyrrolidonecarboxylic acid is used. AD ORiGSMAL 909804/1295