DE2032952C3

DE2032952C3 - Verfahren zur Herstellung von D,L-Penicillamin

Verfahren zur Herstellung von D,L-Penicillamin

Info

Publication number: DE2032952C3
Authority: DE; Germany
Prior art keywords: isopropyl; dimethyl; thiazolidine; carboxylic acid; hydrochloride
Prior art date: 1970-07-03
Legal status : Expired

Application number

DE2032952A

Other languages

German (de)

English (en)

Other versions

DE2032952A1 (en

DE2032952B2 (de

Inventor

Auf Nichtnennung Antrag

Current Assignee

Evonik Operations GmbH

Original Assignee

Deutsche Gold und Silber Scheideanstalt

Priority date

1970-07-03

Filing date

1970-07-03

Publication date

1978-04-27

1970-07-03 Application filed by Deutsche Gold und Silber Scheideanstalt filed Critical Deutsche Gold und Silber Scheideanstalt

1970-07-03 Priority to DE2032952A priority Critical patent/DE2032952C3/de

1971-06-05 Priority to ES71391971A priority patent/ES391971A1/es

1971-06-14 Priority to DK288571A priority patent/DK145180C/da

1971-06-21 Priority to NLAANVRAGE7108503,A priority patent/NL171891C/xx

1971-06-22 Priority to NO2366/71A priority patent/NO136752C/no

1971-06-24 Priority to GB2963571A priority patent/GB1346198A/en

1971-06-25 Priority to RO67459A priority patent/RO59924A/ro

1971-06-26 Priority to EG271/71A priority patent/EG10524A/xx

1971-06-28 Priority to IL37171A priority patent/IL37171A/xx

1971-06-29 Priority to IE829/71A priority patent/IE35409B1/xx

1971-07-01 Priority to YU01739/71A priority patent/YU39160B/xx

1971-07-01 Priority to BE769390A priority patent/BE769390A/xx

1971-07-02 Priority to CS714898A priority patent/CS191251B2/cs

1971-07-02 Priority to SE7108614A priority patent/SE395001B/xx

1971-07-02 Priority to SU1677804A priority patent/SU508207A3/ru

1971-07-02 Priority to ZA714357A priority patent/ZA714357B/xx

1971-07-02 Priority to IT51366/71A priority patent/IT1035036B/it

1971-07-02 Priority to AT576871A priority patent/AT313864B/de

1971-07-02 Priority to CH979471A priority patent/CH575388A5/xx

1971-07-02 Priority to AT819973*1A priority patent/AT322523B/de

1971-07-03 Priority to JP4917971A priority patent/JPS544936B1/ja

1971-07-05 Priority to CA117,354A priority patent/CA949977A/en

1971-07-05 Priority to FR7124505A priority patent/FR2100257A5/fr

1972-03-30 Publication of DE2032952A1 publication Critical patent/DE2032952A1/de

1972-11-14 Priority to AT966672A priority patent/AT319195B/de

1975-07-25 Priority to US05/598,995 priority patent/US4045479A/en

1976-02-13 Priority to US05/657,835 priority patent/US4028406A/en

1977-08-25 Publication of DE2032952B2 publication Critical patent/DE2032952B2/de

1978-04-27 Application granted granted Critical

1978-04-27 Publication of DE2032952C3 publication Critical patent/DE2032952C3/de

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims description 15
VVNCNSJFMMFHPL-UHFFFAOYSA-N penicillamine Chemical compound CC(C)(S)C(N)C(O)=O VVNCNSJFMMFHPL-UHFFFAOYSA-N 0.000 title claims description 3
238000002360 preparation method Methods 0.000 title description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 65
239000000203 mixture Substances 0.000 claims description 30
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 22
150000002825 nitriles Chemical class 0.000 claims description 20
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 claims description 16
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 15
XRKZVUKVOZHPEQ-UHFFFAOYSA-N 5,5-dimethyl-2-propan-2-yl-1,3-thiazolidine-4-carbonitrile Chemical compound CC(C)C1NC(C#N)C(C)(C)S1 XRKZVUKVOZHPEQ-UHFFFAOYSA-N 0.000 claims description 11
235000019270 ammonium chloride Nutrition 0.000 claims description 11
CJCQTPCVKRWSLM-UHFFFAOYSA-N 5,5-dimethyl-2-propan-2-yl-1,3-thiazolidine-4-carboxylic acid;hydrochloride Chemical compound Cl.CC(C)C1NC(C(O)=O)C(C)(C)S1 CJCQTPCVKRWSLM-UHFFFAOYSA-N 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 10
230000007062 hydrolysis Effects 0.000 claims description 10
238000006460 hydrolysis reaction Methods 0.000 claims description 10
229910021529 ammonia Inorganic materials 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 6
JLLDUMMFTKVTLS-UHFFFAOYSA-N 5,5-dimethyl-2-propan-2-yl-1,3-thiazolidine-4-carboxylic acid Chemical compound CC(C)C1NC(C(O)=O)C(C)(C)S1 JLLDUMMFTKVTLS-UHFFFAOYSA-N 0.000 claims description 4
230000015556 catabolic process Effects 0.000 claims description 4
238000006731 degradation reaction Methods 0.000 claims description 4
230000003301 hydrolyzing effect Effects 0.000 claims description 4
238000000926 separation method Methods 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 2
238000010626 work up procedure Methods 0.000 claims description 2
SZLVYXIKAAFTFY-UHFFFAOYSA-N 2-ethyl-1,3-thiazolidine Chemical compound CCC1NCCS1 SZLVYXIKAAFTFY-UHFFFAOYSA-N 0.000 claims 1
125000004093 cyano group Chemical group *C#N 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
238000009835 boiling Methods 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
-1 heterocyclic amines Chemical class 0.000 description 12
238000001816 cooling Methods 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
229960001639 penicillamine Drugs 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
125000005521 carbonamide group Chemical group 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000002904 solvent Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000126 substance Substances 0.000 description 6
238000004821 distillation Methods 0.000 description 4
238000001256 steam distillation Methods 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
VVNCNSJFMMFHPL-GSVOUGTGSA-N L-penicillamine Chemical compound CC(C)(S)[C@H](N)C(O)=O VVNCNSJFMMFHPL-GSVOUGTGSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
150000001875 compounds Chemical class 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000006386 neutralization reaction Methods 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
239000007787 solid Substances 0.000 description 3
FHKABCWCYPPSMO-UHFFFAOYSA-N 5,5-dimethyl-2-propan-2-yl-1,3-thiazolidine-4-carboxamide;hydrochloride Chemical compound Cl.CC(C)C1NC(C(N)=O)C(C)(C)S1 FHKABCWCYPPSMO-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
PRSDPVKGJUBIAA-UHFFFAOYSA-N 1,3-thiazolidine-4-carbonitrile Chemical compound N#CC1CSCN1 PRSDPVKGJUBIAA-UHFFFAOYSA-N 0.000 description 1
OBSLLHNATPQFMJ-UHFFFAOYSA-N 2,4-Dimethylthiazole Chemical compound CC1=CSC(C)=N1 OBSLLHNATPQFMJ-UHFFFAOYSA-N 0.000 description 1
CZDHUFYOXKHLME-UHFFFAOYSA-N 2-amino-3-methyl-3-sulfanylbutanoic acid;hydron;chloride Chemical compound Cl.CC(C)(S)C(N)C(O)=O CZDHUFYOXKHLME-UHFFFAOYSA-N 0.000 description 1
RSZVGLFPGDKTDK-UHFFFAOYSA-N 2-ethyl-1,3-thiazolidin-3-ium-4-carboxylate Chemical compound CCC1NC(C(O)=O)CS1 RSZVGLFPGDKTDK-UHFFFAOYSA-N 0.000 description 1
UEHKBJZDQOQOLX-UHFFFAOYSA-N 5,5-dimethyl-2-propan-2-yl-1,3-thiazolidine Chemical compound CC(C)C1NCC(C)(C)S1 UEHKBJZDQOQOLX-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
FDEQQCOTLPPCAO-UHFFFAOYSA-N Cl.OC(O)=O Chemical compound Cl.OC(O)=O FDEQQCOTLPPCAO-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
206010011778 Cystinuria Diseases 0.000 description 1
208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
208000018839 Wilson disease Diseases 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
KHPLPBHMTCTCHA-UHFFFAOYSA-N ammonium chlorate Chemical compound N.OCl(=O)=O KHPLPBHMTCTCHA-UHFFFAOYSA-N 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
239000000110 cooling liquid Substances 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
FOBPTJZYDGNHLR-UHFFFAOYSA-N diphosphorus Chemical compound P#P FOBPTJZYDGNHLR-UHFFFAOYSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000006052 feed supplement Substances 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229920001021 polysulfide Polymers 0.000 description 1
239000005077 polysulfide Substances 0.000 description 1
150000008117 polysulfides Polymers 0.000 description 1
239000000047 product Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001226 reprecipitation Methods 0.000 description 1
238000003385 ring cleavage reaction Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1