GB2051797A - Process for production of beta- chloroalanine - Google Patents
Process for production of beta- chloroalanine Download PDFInfo
- Publication number
- GB2051797A GB2051797A GB8017729A GB8017729A GB2051797A GB 2051797 A GB2051797 A GB 2051797A GB 8017729 A GB8017729 A GB 8017729A GB 8017729 A GB8017729 A GB 8017729A GB 2051797 A GB2051797 A GB 2051797A
- Authority
- GB
- United Kingdom
- Prior art keywords
- amino
- chloroacetaldehyde
- chloroalanine
- solution
- reaction mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 10
- ASBJGPTTYPEMLP-UHFFFAOYSA-N 3-chloroalanine Chemical compound ClCC(N)C(O)=O ASBJGPTTYPEMLP-UHFFFAOYSA-N 0.000 title abstract description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 48
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims abstract description 36
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000007864 aqueous solution Substances 0.000 claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims abstract description 20
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 20
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 230000002378 acidificating effect Effects 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 38
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 239000001569 carbon dioxide Substances 0.000 claims description 14
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 14
- -1 alkali metal salts Chemical class 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 150000003863 ammonium salts Chemical class 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- PQUCIEFHOVEZAU-UHFFFAOYSA-N Diammonium sulfite Chemical compound [NH4+].[NH4+].[O-]S([O-])=O PQUCIEFHOVEZAU-UHFFFAOYSA-N 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- WNFAWINJBNDQLB-UHFFFAOYSA-N 2-amino-3-chloropropanenitrile Chemical compound ClCC(N)C#N WNFAWINJBNDQLB-UHFFFAOYSA-N 0.000 abstract 2
- 239000011541 reaction mixture Substances 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 14
- 239000013078 crystal Substances 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000007789 gas Substances 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- AOSFMYBATFLTAQ-UHFFFAOYSA-N 1-amino-3-(benzimidazol-1-yl)propan-2-ol Chemical group C1=CC=C2N(CC(O)CN)C=NC2=C1 AOSFMYBATFLTAQ-UHFFFAOYSA-N 0.000 description 5
- RDXMEUDCEWSFDP-UHFFFAOYSA-N 3-chloro-2-hydroxypropanenitrile Chemical compound ClCC(O)C#N RDXMEUDCEWSFDP-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 229960003750 ethyl chloride Drugs 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YOVHDCFHDVHTPM-DKWTVANSSA-N (2s)-2-(chloroamino)propanoic acid;hydrochloride Chemical compound Cl.ClN[C@@H](C)C(O)=O YOVHDCFHDVHTPM-DKWTVANSSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 238000007059 Strecker synthesis reaction Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 125000005219 aminonitrile group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229940086542 triethylamine Drugs 0.000 description 2
- SVONRAPFKPVNKG-UHFFFAOYSA-N 2-ethoxyethyl acetate Chemical compound CCOCCOC(C)=O SVONRAPFKPVNKG-UHFFFAOYSA-N 0.000 description 1
- OSLCJYYQMKPZHU-UHFFFAOYSA-N 3-chlorolactic acid Chemical compound ClCC(O)C(O)=O OSLCJYYQMKPZHU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- NEAPKZHDYMQZCB-UHFFFAOYSA-N N-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]ethyl]-2-oxo-3H-1,3-benzoxazole-6-carboxamide Chemical compound C1CN(CCN1CCNC(=O)C2=CC3=C(C=C2)NC(=O)O3)C4=CN=C(N=C4)NC5CC6=CC=CC=C6C5 NEAPKZHDYMQZCB-UHFFFAOYSA-N 0.000 description 1
- 229910003202 NH4 Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910006069 SO3H Inorganic materials 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960003077 cycloserine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000000361 pesticidal effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A novel production process of beta -chloroalanine from chloroacetaldehyde is provided. In this process, a bisulfite or sulfite addition compound of chloroacetaldehyde is first reacted, in an aqueous solution, with ammonia and, then, reacted with hydrocyanic acid or a salt thereof. Thus, alpha -amino- beta - chloropropionitrile is formed. This alpha - amino- beta -chloropropionitrile is hydrolyzed under an acidic condition to form beta -chloroalanine.
Description
SPECIFICATION
Process for production of beta-chloroalanine
The present invention relates to a process for preparing ss-chloroalanine. More specifically, it relates to a process for preparing ss-chloroalanine by reacting a bisulfite or sulfite addition compound of chloroacetaldehyde, in an aqueous solution, first with ammonia and, then, with hydrocyanic acid or a salt thereof, followed by hydrolysis of the formed a-amino-ss-chloropropionitrile under an acidic condition.
Beta-chloroalanine itself is one of amino acids having physiological activity (cf. J. Biol. Chem. 252, 3170).
Beta-chloroalanine is also useful as an intermediate for the synthesis of, for example, various pharmaceutical compounds and pesticidal compounds, such as, antibiotics (e.g. cycloserine) and sulfur containing amino acids (e.g. cystine) or cystein.
However, since a production process of ss-chloroalanine, which would be industrially advantageous from an economical point of view, has not been known, ss-chloroalanine is not widely used so an intermediate for the synthesis of pharmaceutical compounds and pesticides. For instance, known methods for producing ss-chloroalanine are a method for substituting chlorine for the hydroxyl group of serine (cf. J. Chem. Soc. p.
1968, 1969) and a method for the chlorination of cystine (cf. Ber. 93, p 782, 1960). However, since expensive starting materials are used in these methods, these methods are not suitable for use in the industrial production of (3-chloroalanine.
Furthermore, a so-called Strecker synthesis is well-known for the industrial synthesis of amino acids.
However, ss-chloroalanine has not been obtained from the corresponding aldehyde, chloroacetaldehyde, by
Strecker synthesis. That is, when chloroacetaldehyde is reacted with hydrocyanic acid and ammonia, ss-chlorolactonitrile, which is formed by the addition of a cyano group of chloroacetaldehyde, is produced.
However, since the amination of the hydroxyl group of the formed, ss-chlorolactonitrile with ammonia is extremely difficult, the desired a-amino-ss-chloropropionitrile which is the intermediate for the synthesis of ss-chloroalanine cannot be obtained. Even in the case where chloroacetaldehyde is first reacted with ammonia to form a-amino--chlornethanol and then reacted with hydrocyanic acid or the salts thereof, a-amino-ss-chloropropionitrile cannot be formed, but ss-chlorolactonitrile is formed by the replacement of the amino group of a a-amino-f3-chloroethanol with a cyano group.Furthermore, in the case where ss-chlorolactonitrile is reacted with concentrated ammonia under severe reaction conditions for the purpose of the production of c!-amino-ss-chloropropionitrile, the decomposition of ss-chlorolactonitrile occurs.
Accordingly, an object of the present invention is to obviate the above-mentioned problems of the prior arts and to provide a process for preparing ss-chloroalanine from chloroacetaladehyde at a high selectivity.
Other objects and advantages of the present invention will be apparent from the description set forth hereinbelow.
In accordance with the present invention, there is provided a process for preparing ss-chloroalanine comprising the steps of:
(a) reacting an aqueous solution of a bisulfite or sulfite addition compound of chloroacetaldehyde with ammonia and, then, with hydrocyanic acid or a salt thereof, whereby a-amino-p-chloropropionitrile is formed, and
(b) hydrolyzing the resultant a-amino--chlornpropionitrile under an acidic condition.
The present invention will be better understood from the description set forth below with reference to the accompanying drawings wherein:
Figures land 2 illustrate the mass spectrum and IR spectrum of the intermediate, a-amino-ss-chloroethane sulfonic acid, respectively;
Figure 3 illustrates the mass spectrum of the intermediate, ct-amino-p-chloropropionitrile; Figure 4 illustrates the IR spectrum of o!-amino-ss-chloropropionitrile hydrochloride; and
Figure 5 illustrates the NMR spectrum of ct-amino-P-chloropropionitrile.
The bisulfite addition compound of chloroacetaldehyde can be readily obtained by reacting approximately equimolar amounts of chloroacetaldehyde and bisulfite with each other in an aqueous solution at room temperature. Any water-soluble bisulfites can be used in the formation of the bisulfite addition compound of chloroacetaldehyde. Examples of the typical bisulfites are: alkali metal salts such as lithium, sodium, potassium and the like; alkaline earth metal salts such as calcium, magnesium and the like; and an ammonium salt. The most preferable bisulfite is ammonium bisulfite.
Although the amounts of the bisulfites and the chloroacetaldehyde used in the formation of the bisulfite addition compounds may be varied over a wide range, the molar ratio of bisulfite to chloroacetaldehyde is preferably 1:0.8-1.2. Although a further excess amount of either compound can be used, the use of an excess amount of either component not only causes no advantageous result, but is also uneconomical. Further, there is a fear that the use of an excess amount of either component produces undesirable by-products.
In lieu of the bisulfites, ammonium sulfite can be used in the formation of the sulfite addition compound of chloroacetaldehyde. However, the use of the other sulfites, such as alkali metal sulfites and alkaline earth metal sulfites, it not suitable in the formation of the sulfite addition compound of chloroacetaldehyde, since the formed sulfite addition compound does not form the desired a-amino-ss-chloroethane sulfonates at a good yield, in the subsequent reaction step. Similarly, in the case where bisulfite is reacted with chloroacetaldehyde under an alkaline condition, ammonium bisulfite should be used. This is because, when bisulfite is reacted with chloroacetaldehyde under an alkaline condition, the corresponding sulfite is substantially reacted with chloroacetaldehyde to form the sulfite addition compound of chloroacetaldehyde.
The bisulfite (or sulfite) addition compound of chloroacetaldehyde is, then, reacted with ammonia in an aqueous medium. The ammonia can be used in the form of gaseous ammonia, liquid ammonia or the aqueous solution thereof. Although the amount of ammonia used in the reaction may be varied depending upon the kinds of the bisulfites and the sulfite and gaseous ammonia, liquid ammonia or the aqueous solution thereof, the molar ratio of ammonia to chloroacetaldehyde should be preferably within the range of from 1 to 5, more preferably 2 to 4. Although there is no critical reaction temperature or reaction time, this reaction is generally carried out within a temperature of from 0 to 50"C, more preferably 20 to 300C for 0.5 through 2 hours.Thus, a-amino-P-chloroethane sulfonates CICH2CH(NH2)SO3M (M=NH4, Na, K, 1/2Ca, 1/2Mg etc.) are obtained. These a-amino-p-chloroethane sulfonates and a-amino-ss-chloroethane sulfonic acid are novel compounds. The a-amino-p-chlornethane sulfonic acid or the salts thereof can be recovered from the aqueous solution containing the same by neutralizing the excess amount of ammonia with a mineral acid (e.g. sulfuric acid, hydrochloric acid) and by lowering the pH of the solution to an isoelectric point. The mass spectrum and IR spectrum of the a-amino-ss-chioroethane sulfonic acid CICH2CH(NH2)SO3H are illustrated in Figures 1 and 2, respectively.
The result of elemental analysis of a-amini-ss-chloroethane sulfonic acid thus obtained is as follows.
Found: H 3.71%; C 15.31%; N 8.17%; Cl 21.84%;
Calculation (as C2H6NO3SCI)
H 3.79%; C 15.05%;
N 8.78%; Cl 22.22%
The ct-amino--chlornethanesulfonate obtained by the reaction of the bisulfite (or sulfite) addition compound of chloroacetaldehyde and ammonia is reacted with hydrocyanic acid or the salts thereof (e.g.
alkali metal salts, alkaline earth metal salts or ammonium salt) to form a-amino-ss-chloropropionitrile. Since a-amino-ss-chloropropionitrile is a very unstable substance, especially in an aqueous solution, special caution must be taken during the process of this reaction.
For example, the reaction is carried out by using a suitable organic solvent, which is not miscible with water, so that the formed a-amino-ss-chloropropionitrile is rapidly transferred into an organic phase. Of course, once a-amino--chlornethane sulfonate is separated from an aqueous reaction mixture, the separated a-amino-ss-chloroethane sulfonate can be reacted with hydrocyanic acid or the salts thereof in a suitable organic solvent. Preferably, while the reaction is carried out by using an apparatus in which a reactor is connected with an extractor and a decanter, the a-amino-ss-chloropropionitrile produced in the reaction is continuously extracted with a suitable organic solvent from the aqueous reaction mixture.
The organic solvents used in this reaction should be those which are stable under the reaction conditions, which neither react with nor decompose the reactants or the product, which do not readily dissolve the reactants, but readily dissolve the product, and which do not react with hydrogen chloride. Examples of such an organic solvent are carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, n-hexane, n-pentane, cyclohexane, diethyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, ethylbenzene and the like. The most preferable organic solvent is ethylacetate, ethyleneglycol monoethyl ether acetate, propionitrile or propylene carbonate.
The amount of hydrocyanic acid or the salts thereof (e.g. sodium cyanide, potassium cyanide) used in this reaction is preferably a stoichiometric amount or more. Practically speaking, the amount of hydrocyanic acid orthe salts thereof is, more preferably, within the range of from 2.0 to 5.0 mol, based on 1 mol of a-amino-ss-chloroethane sulfonate. Although there is no critical reaction temperature or reaction time, the reaction is preferably carried out at a temperature of from 0 to 30"C, more preferably 5 to 10 C, for 5 through 24 hours.
The obtained a-amino-ss-chloropropionitrile and the salts thereof are also novel compounds. Since the resultant a-amino-ss-chloropropionitrile is an unstable substance, the product is recovered, as hydrochloride, by introducing dry hydrogen chloride gas into the organic solution containing the same. The a-amino-(3- chloropropionitrile hydrochloride is precipitated, as crystals, in the organic solution and can be isolated in a known manner.
The mass spectrum of a-amino-l-3-chloropropionitrile thus obtained is illustrated in Figure 3. The IR spectrum of a-amino-ss-chloropropionitrile hydrochloride is illustrated in Figure 4 and the NMR spectrum of a-amino-p-chloropropionitrile is illustrated in Figure 5.
The result of an elemental analysis of a-amino-ss-chloropropionitrile hydrochloride is as follows.
Found: H 4.80%; C 24.05%;
N 19.60%; Cl 53.00%
Calculation (as C3H6N2C12):
H 4.29%; C 25.56%; N 19.87%; Cl 50.29%
According to the present invention, the formed a-amino-ss-chloropropionitrile in an organic solution is hydrolyzed by the addition of mineral acids, such as hydrychloric acid, sulfuric acid, nitric acid and the like, after the aqueous solution phase, if present, is separated from the organic solution phase. The organic solution is heated to evaporate the organic solvent off and, then, is subjected to hydrolysis under an acidic condition at a temperature of, for example, 80 through 100 C for 0.5 through 2 hours. Thus, P-chloroalanine is formed in an aqueous mineral salt solution. The ss-chloroalanine can be recovered as follows.
For instance, the aqueous solution containing ss-chloroalanine is first concentrated and, then, alcohols, such as methanol, ethanol and the like, are added thereto. Thus, the ammonium salt of the mineral acids are crystallized out of the solution. The resultant alcohol solution is separated from the crystallized ammonium salt and, then, a suitable solvent, such as an ether, is added to the separated alcohol solution to crystallize the mineral acid salt of B-chloroalanine. The crystals can be purified by a conventional technique, such as recrystallization. Furthermore, if necessary, ss-chloroalanine can be recovered, as a free amino acid, by the neutralization of the alcohol solution of the mineral acid salt of ss-chloroalanine with an equimolar amount of, for example, pyridine and triethylamine.
According to the present invention, ss-chloroalanine can be obtained at a very high selectivity without causing any substantial formation of ss-chlorolactic acid.
The present inventors have further found that, when carbon dioxide is added to the a-amino-ss- chloropropionitrile solution prior to the hydrolysis of the a-amino-p-chlornprnpionitrile under an acidic condition, the a-amino-ss-chloropropionitrile can be stabilized and, therefore, ss-chloroalanine having a high purity can be obtained at a high yield by the hydrolysis of a-amino-t3-chlornprnpionitrile. The carbon dioxide can be used either in the form of a gas or a solid.Although there is no critical amount of carbon dioxide introduced into the aqueous a-amino-ss-chloropropionitrile solution, generally speaking, the amount of the carbon dioxide is such that the pH of the aqueous solution becomes 7 through 6 or such that the absorbed amount of the carbon dioxide becomes 0.5 through 1.0 mol based on 1 mole of the a-amino-pchloropropionitrile. In order to accelerate the absorption of the carbon dioxide, the aqueous a-amino-ss- chloropropionitrile solution can be cooled to a temperature of 10 C or less. Since the absorption rate of the carbon dioxide increases with the increase in the concentration of the aminonitrile, the concentration of the aminonitrile is advantageously adjusted to 20 through 60%, more preferably 40 through 50%.
The present invention is now illustrated by, but is by no means limited to, the following examples, in which all percentages are expressed on a weight basis unless otherwise noted.
Example 1
32 g of sodium bisulfite addition compound of chloroacetaldehyde was dissolved in a mixture of 50 ml of 28% concentrated ammonia water and 50 ml of water and the resultant mixture was allowed to react for 1 hour at room temperature. To the reaction mixture 100 ml of ethyl ether was added. After that, 9 of sodium cyanide dissolved in 30 ml of water was dropwise added to the reaction mixture over 15 minutes, while the reaction mixture was maintained at a temperature of -10 C. Then, while the reaction mixture was maintained at a temperature of from -5 C to 5"C, the reaction mixture was allowed to react for 6 hours with vigorous agitation.
After the completion of the reaction, the reaction mixture was allowed to stand, whereby the ether solution was separated. After removing the ether solution from the aqueous solution, the resultant aqueous solution was extracted with 100 ml of fresh ether. The ether solutions were combined and, then, 50 ml of concentrated hydrochloric acid was gradually added thereto. After that, ether was distilled off and the resultant aqueous solution was heated and concentrated on a boiling water bath for 1 hour. To the concentrated aqueous solution, 30 ml of ethanol was added, whereby ammonium chloride was precipitated.
To the separated ethanol solution, 100 ml of ether was added to precipitate 14 g of ss-chloroalanine hydrochloride. The mol yield of the ss-chloroalanine thus obtained was 50%.
Example 2
47 9 of 50% aqueous solution of chloroacetaldehyde was mixed with 60 g of 50% aqueous solution of ammonium bisulfite and, then, the mixture was allowed to react for 1 hour at room temperature. 50 ml of 28% ammonia water was added to the mixture and was allowed to react for a further 1 hour at room temperature. After that, 100 ml of ethyl ether was added and, then, 50 ml of an aqueous solution containing 14.7 g of sodium cyanide was dropwise added thereto over 15 minutes under vigorous agitation, while the reaction mixture was kept at a temperature of 1 0 C or less. The reaction mixture was allowed to react for 12 hours. After the completion of the reaction, the reaction mixture was treated in a manner as described in
Example 1. Thus, 25.5 g of 13-chloroalanine hydrochloride was obtained.
Example 3
32 g of sodium bisulfite was dissolved in 60 ml of water and, then, 26.3 g of the hemi-hydrate crystal of chloroacetaldehyde was added thereto. After that, the mixture was allowed to react for 2 hours at room temperature. 60 ml of 28% ammonia water was added to the reaction mixture and, then, the reaction mixture was allowed to react for a further 1 hour at room temperature.
The reaction mixture thus obtained was treated in a manner as described in Example 1, except that triethyl amine was added to the alcoholic solution of p-chlornalanine hydrochloride, in lieu of ethyl ether, at the final step. Thus, the crystals of frchlornalanine were precipitated by neutralization. The yield of ,8-chloroalanine was 22 g.
Example 4
54 g ammonium bisulfite addition compound of chloroacetaldehyde was dissolved in 50 ml of water and, then, 60 ml of ammonia water was added thereto. This mixture was allowed to react for 1 hour at room temperature. After 100 ml of ethyl ether was added to the reaction mixture, 50 ml of an aqueous sodium cyanide solution containing 14.7 g of sodium cyanide was dropwise added to the reaction mixture over 15 minutes, while the reaction mixture was maintained at a temperature of 10"C or iess. The reaction mixture was allowed to react for 15 hours at a temperature of 10 C with vigorous agitation.
After the completion of the reaction, the separated ether solution was removed from the aqueous solution and the resultant aqueous solution was extracted with 100 ml of fresh ether. The ether solutions were combined and, then, the combined solution was dried over anhydrous magnesium sulfate.
After the desiccant was removed, dry hydrogen chloride was introduced into the ether solution, while cooling with ice-water, whereby the ether solution was saturated with hydrogen chloride. Thus, z-amino-p-chlornprnpionitrile hydrochloride was precipitated. The crystals thus precipitated were separated from ether and dissolved in 30 ml of concentrated hydrochloric acid solution. The solution was heated and concentrated on a boiling water bath for 1 hour. To the concentrate, 50 ml of ethanol was added and the insoluble ammonium chloride was separated. 150 ml of ethyl ether was added to the resultant ethanol solution. Thus, 30 g of B-chloroalanine hydrochloride crystals were obtained.
Example 5
7 g of hemi-hydrate crystals of chloroacetaldehyde were completely dissolved in 16 g of a 50% aqueous ammoniu m bisulfite solution. Then, 25 ml of a 30% aqueous ammonia solution was added to the solution.
After that, while ammonia gas was introduced into the mixture so that the mixture was saturated with ammonia, the mixture was allowed to react for 2 hours at room temperature. After the completion of the amination reaction, the reaction mixture was cooled to a temperature of 10C or less, 15 ml of an 80% aqueous hydrocyanic acid was dropwise added to the reaction mixture, while ammonia gas was introduced into the reaction mixture. After the dropwise addition of the hydrogen cyanide, the reaction mixture was allowed to react for 3 hours at a temperature of 10"C or less. After that, the reaction mixture was concentrated on a water bath having a temperature of 40"C for 5 minutes under a reduced pressure of 4 through 6 mmHg.
The weight of the reaction mixture was decreased by approximately 15 g and the pH of the reaction mixture became 7 through 8. The unreacted amonia and hydrogen cyanide were substantially evaporated.
While the reaction mixture was cooled, carbon dioxide gas was introduced and absorbed into the reaction mixture became 7 through 8. The unreacted ammonia and hydrogen cyanide were substantially evaporated.
reaction mixture and the pH of the reaction mixture became 6 through 7.
To the reaction mixture, 30 ml of concentrated hydrochloricacid solution was gradually added in a manner such that the temperature of the reaction mixture was not raised beyond 20"C. In time, white precipitates were formed. The precipitates were separated from the reaction mixture by filtration. The filtrate was evaporated to a dry state under a reduced pressure. To the residue, 40 ml of concentrated hydrochloric acid solution was added and the mixture was hydrolyzed for 1 hour at a temperature of 95 through 100"C. After the hydrolysis, the mixture was evapolated to a dry state under a reduced pressure. The resultant B-chloroalanine hydrochloride was extracted with 100 ml of absolute ethanol and the insoluble ammonium chloride was removed. Ethanol was distilled offfrom the ethanol solution and 8.32 g ofchloroalanine hydrochloride crystals were obtained. The yield was 65%.
In the case where the above-mentioned Example 5 was repeated, except that the introduction of carbon dioxide gas was not carried out, 5 g of ss-chloroalanine hydrochloride in the form of colored tar was obtained (yield 39%).
Example 6 ss-chloroalanine was prepared from 7 g of hemi-hydrate crystals of chloroacetaldehyde in a manner as described in Example 5, except that hydrogen chloride was gradually absorbed, after the absorption of carbon dioxide gas, in lieu of the addition of 30 ml of concentrated hydrochloric acid solution. After 20 g of hydrogen chloride was absorbed, the precipitated, inorganic salt was removed by filtration and the filtrate was evaporated to a dry state.
The resultant a-amino-p-chloropropionitrile hydrochloride was hydrolyzed in a manner as described in
Example 5. As a result, 8 g of p-chloroalanine hydrochloride crystals were obtained. The yield was 62.5%.
Example 7
26.3 g (0.3 mol) of hemi-hydrate crystals of chloroacetaldehyde were completely dissolved in 62 g (0.31 mol) of a 50% aqueous ammonium bisulfite solution. This aqueous solution was placed in a reactor provided with a perforated plate therein and connected to a decanter. To this aqueous solution, 100 ml of 30% aqueous solution of ammonia was added and, further, ammonia gas was introduced, whereby the aqueous solution was saturated with ammonia. After that, the aqueous solution was allowed to react for 2 hours at room temperature. The reaction mixture was cooled at 10 C. While the reaction mixture was maintained at a temperature of 1 0'C and while ammonia gas was introduced into the reaction mixture, 19.7 mi (0.6 mol) of a 50% hydrocyanic acid was added to the reaction mixture.After the addition of the hydrocyanic acid, methylene chloride was introduced into the reaction mixture, while the reaction mixture was vigorously stirred. The methylene chloride layer was collected below the perforated plate fixed to the bottom portion of the reactor. The methylene chloride layer was successively siphoned to the decanter, wherein the aqueous layer was separated from the methylene chloride layer and was returned to the reactor. The separated methylene chloride solution was withdrawn from the decanter and collected in a reservoir.
In a manner as mentioned above, the extraction reaction were carried out for 3 hours, while methylene chloride was introduced into the reaction mixture at a rate of 5 ml/min. Thus, 900 ml of methylene chloride was introduced. During the extraction reaction, the reaction mixture was maintained at a temperature of 10"C.
The methylene chloride solution collected in the reservoir was distilled off at a temperature of 20 through 30"C under a reduced pressure and the resultant liquid a-amino-P-chloropropionitrile was dissolved in 40 ml of distilled water in another vessel. Carbon dioxide gas was introduced into the mixture for 30 minutes with vigorous stirring. After the introduction of the carbon dioxide, the pH of the mixture became 7. Therefore, 100 ml of concentrated hydrochloric acid solution was added to the mixture and, then, the mixture was hydrolyzed for 1 hour at a temperature of 95"C. After the hydrolysis, the reaction mixture was evaporated to a dry state. The residue was extracted with 100 ml of absolute ethanol and the insoluble ammonium chloride was removed. Ethanol was distilled off.As a result, 31.2 g of chloroalanine hydrochloride were obtained. The yield was 65%.
In the case where the above-mentioned Example 7 was repeated, except that the neutralization of a-amino-ss-chloropropionitrile with carbon dioxide gas was not carried out, 28 g of chloroalanine hydrochloride contaminated with brown tar substances were obtained. The yield was 59.5%.
Example 8 ss-chloroalanine was prepared from 26.3 g of hemi-hydrate crystals of chloroacetaldehyde in a manner as described in Example 7, except that (1) 32 ml of 70% hydrocyanic acid were used, (2) the extraction reaction time was 2.5 hours and (3) the total amount of the methylene chloride used in the extraction was 700 ml.
36 g of ss-chloroalanine hydrochloride were obtained. The yield was 75%.
Example 9 (3-chloroalanine was prepared in a manner as described in Example 7, except that (1) 46 ml of 90% hydrocyanic acid was used, (2) the extraction reaction time was 1.5 hours and (3) the total amount of the methylene chloride used in the extraction was 500 ml.
40 g of ss-chloroalanine hydrochloride were obtained. The yield was 85%.
Claims (5)
1. A process for preparing íj-chloroalanine comprising the steps of:
(a) reacting an aqueous solution of a bisulfite or sulfite addition compound of chloroacetaldehyde with ammonia and, then, with hydrocyanic acid or a salt thereof, whereby a-amino-B-chlorapropionitrile is formed, and
(b) hydrolyzing the resultant a-amino43-chlornprnpionitrile under an acidic condition.
2. A process as claimed in claim 1, wherein said bisulfite addition compound of chloroacetaldehyde is derived from the reaction of a water-soluble bisulfite and chloroacetaldehyde.
3. A process as claimed in claim 2, wherein said water-soluble bisulfite is selected from the alkali metal salts, the alkaline earth metal salts and an ammonium salt.
4. A process as claimed in claim 1, wherein said sulfite addition compound of chloroacetaldehyde is derived from the reaction of ammonium sulfite and chloroacetaldehyde.
5. A process as claimed in claim 1, wherein said hydrolysis under an acidic condition is carried out after carbon dioxide is added to the resultant ct-amino-p-chloropropionitrile solution.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP54071165A JPS5822140B2 (en) | 1979-06-08 | 1979-06-08 | Production method of β-chloroalanine |
JP3907080A JPS5949219B2 (en) | 1980-03-28 | 1980-03-28 | Production method of β-chloroalanine |
Publications (2)
Publication Number | Publication Date |
---|---|
GB2051797A true GB2051797A (en) | 1981-01-21 |
GB2051797B GB2051797B (en) | 1983-02-02 |
Family
ID=26378394
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8017729A Expired GB2051797B (en) | 1979-06-08 | 1980-05-30 | Process for production of beta-chloro-alanine |
Country Status (7)
Country | Link |
---|---|
CA (1) | CA1111444A (en) |
CH (1) | CH643528A5 (en) |
DE (1) | DE3021566A1 (en) |
ES (1) | ES8104196A1 (en) |
FR (1) | FR2458537B1 (en) |
GB (1) | GB2051797B (en) |
IT (1) | IT1130477B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4484003A (en) * | 1981-05-18 | 1984-11-20 | Mitsui Toatsu Chemicals, Incorporated | Preparation process of β-chloroalanine |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1057651A (en) * | 1963-01-16 | 1967-02-08 | Merck & Co Inc | Chlorinated amino acids and their preparation |
US3903150A (en) * | 1972-02-03 | 1975-09-02 | Merck & Co Inc | Process for preparing 3-fluoro-D-alanine |
-
1980
- 1980-05-26 CA CA352,668A patent/CA1111444A/en not_active Expired
- 1980-05-30 GB GB8017729A patent/GB2051797B/en not_active Expired
- 1980-06-05 IT IT67867/80A patent/IT1130477B/en active
- 1980-06-06 CH CH438080A patent/CH643528A5/en not_active IP Right Cessation
- 1980-06-06 FR FR8013036A patent/FR2458537B1/en not_active Expired
- 1980-06-06 ES ES492210A patent/ES8104196A1/en not_active Expired
- 1980-06-07 DE DE19803021566 patent/DE3021566A1/en active Granted
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4484003A (en) * | 1981-05-18 | 1984-11-20 | Mitsui Toatsu Chemicals, Incorporated | Preparation process of β-chloroalanine |
Also Published As
Publication number | Publication date |
---|---|
DE3021566C2 (en) | 1990-05-03 |
FR2458537B1 (en) | 1985-07-05 |
ES492210A0 (en) | 1981-04-01 |
CA1111444A (en) | 1981-10-27 |
FR2458537A1 (en) | 1981-01-02 |
IT8067867A0 (en) | 1980-06-05 |
GB2051797B (en) | 1983-02-02 |
DE3021566A1 (en) | 1981-01-15 |
CH643528A5 (en) | 1984-06-15 |
IT1130477B (en) | 1986-06-11 |
ES8104196A1 (en) | 1981-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4283554A (en) | Process for production of β-chloroalanine | |
CA1111444A (en) | Process for production of beta-chloroalanine | |
US4235812A (en) | Process for preparing thiourea dioxide | |
JPS5829296B2 (en) | Method for producing monomethylhydrazine | |
US4254281A (en) | Novel vitamin A acetate process | |
RU2001909C1 (en) | Method of captopril synthesis | |
JPS63192750A (en) | Improved manufacture of alkane sulfonamide | |
CA2001876A1 (en) | Preparation of alkanesulfonamides | |
EP0844239B1 (en) | Method for producing homocystine | |
JP2001247529A (en) | Method of producing alpha-amino acid amide | |
JPS5949219B2 (en) | Production method of β-chloroalanine | |
JP4250780B2 (en) | Method for producing mercaptocarboxylic acids | |
RU2135463C1 (en) | Method of synthesis of trifluoromethane sulfoacid | |
US4070363A (en) | Manufacture of tetramisole | |
JPS6127980A (en) | Preparation of hydroxyflavan compound | |
JPS63243066A (en) | Production of 2-aminoethanesulfonic acid | |
JP2907520B2 (en) | Method for producing surfactant | |
JPS6115872B2 (en) | ||
KR101170192B1 (en) | One-pot process for producing 1,2-benzisoxazole-3-methanesulfonamide | |
US4515958A (en) | Process for preparing 1-alkyl-5-mercaptotetrazoles | |
EP0151835B1 (en) | Process for producing pentachloronitrobenzene from hexachlorobenzene | |
JPS62267253A (en) | Production of alpha-amino acid | |
US3043864A (en) | Process for the production of cyclohexylsulfamates | |
KR800001550B1 (en) | Preparing process for 5-(4-hyroxy phenyl)hydantoins | |
US4549028A (en) | Process for the preparation of hydantoin precursor of phenylalanine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PE20 | Patent expired after termination of 20 years |
Effective date: 20000529 |