CN104892521A - Synthesis and purification method for alpha-amino acid compound - Google Patents
Synthesis and purification method for alpha-amino acid compound Download PDFInfo
- Publication number
- CN104892521A CN104892521A CN201510113479.4A CN201510113479A CN104892521A CN 104892521 A CN104892521 A CN 104892521A CN 201510113479 A CN201510113479 A CN 201510113479A CN 104892521 A CN104892521 A CN 104892521A
- Authority
- CN
- China
- Prior art keywords
- amino acid
- synthesis
- alpha
- acid compounds
- purification process
- 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
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 39
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 37
- -1 alpha-amino acid compound Chemical class 0.000 title claims abstract description 22
- 238000000746 purification Methods 0.000 title claims abstract description 19
- 235000008206 alpha-amino acids Nutrition 0.000 title abstract 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003513 alkali Substances 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 229940091173 hydantoin Drugs 0.000 claims abstract description 9
- 238000004064 recycling Methods 0.000 claims abstract description 9
- 229910044991 metal oxide Inorganic materials 0.000 claims abstract description 7
- 150000004706 metal oxides Chemical class 0.000 claims abstract description 7
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims abstract description 6
- 239000012046 mixed solvent Substances 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 56
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 28
- 235000011089 carbon dioxide Nutrition 0.000 claims description 19
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 18
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 15
- 229910021529 ammonia Inorganic materials 0.000 claims description 14
- 238000006460 hydrolysis reaction Methods 0.000 claims description 14
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 11
- 239000000292 calcium oxide Substances 0.000 claims description 11
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 11
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 238000001354 calcination Methods 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 230000001476 alcoholic effect Effects 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000011575 calcium Chemical group 0.000 claims description 6
- 229910052791 calcium Inorganic materials 0.000 claims description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 6
- 239000011777 magnesium Chemical group 0.000 claims description 6
- 229910052749 magnesium Chemical group 0.000 claims description 6
- 239000000395 magnesium oxide Substances 0.000 claims description 6
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 6
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 6
- 238000006386 neutralization reaction Methods 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 239000001095 magnesium carbonate Substances 0.000 claims description 4
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 4
- 235000014380 magnesium carbonate Nutrition 0.000 claims description 4
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 4
- 229960001708 magnesium carbonate Drugs 0.000 claims description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 235000019270 ammonium chloride Nutrition 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 3
- 230000003472 neutralizing effect Effects 0.000 claims description 3
- LQOBMKYCRQDMTN-UHFFFAOYSA-N 3-(2-ethylphenyl)pentan-3-amine;hydrochloride Chemical compound Cl.CCC1=CC=CC=C1C(N)(CC)CC LQOBMKYCRQDMTN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004254 Ammonium phosphate Substances 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- UZJRFKQXVFFFEZ-UHFFFAOYSA-N P.C(C)C1=C(C(OS(O)(=O)=O)(CC)CC)C=CC=C1 Chemical compound P.C(C)C1=C(C(OS(O)(=O)=O)(CC)CC)C=CC=C1 UZJRFKQXVFFFEZ-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 2
- BIGPRXCJEDHCLP-UHFFFAOYSA-N ammonium bisulfate Chemical compound [NH4+].OS([O-])(=O)=O BIGPRXCJEDHCLP-UHFFFAOYSA-N 0.000 claims description 2
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 claims description 2
- 229910000148 ammonium phosphate Inorganic materials 0.000 claims description 2
- 235000019289 ammonium phosphates Nutrition 0.000 claims description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 2
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 2
- UIMNEJWWTRUAFH-UHFFFAOYSA-L benzyl(triethyl)azanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CC[N+](CC)(CC)CC1=CC=CC=C1.CC[N+](CC)(CC)CC1=CC=CC=C1 UIMNEJWWTRUAFH-UHFFFAOYSA-L 0.000 claims description 2
- OZXRLJIEKITDLN-UHFFFAOYSA-M benzyl(triethyl)phosphanium;chloride Chemical compound [Cl-].CC[P+](CC)(CC)CC1=CC=CC=C1 OZXRLJIEKITDLN-UHFFFAOYSA-M 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- IBIRZFNPWYRWOG-UHFFFAOYSA-N phosphane;phosphoric acid Chemical compound P.OP(O)(O)=O IBIRZFNPWYRWOG-UHFFFAOYSA-N 0.000 claims description 2
- FRXLZEVXYFDHIM-UHFFFAOYSA-N phosphanium;hydrogen sulfate Chemical compound [PH4+].OS([O-])(=O)=O FRXLZEVXYFDHIM-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 abstract 2
- 239000001099 ammonium carbonate Substances 0.000 abstract 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 abstract 1
- 229910013703 M(OH)x Inorganic materials 0.000 abstract 1
- 235000012501 ammonium carbonate Nutrition 0.000 abstract 1
- 239000001569 carbon dioxide Substances 0.000 abstract 1
- 229910002092 carbon dioxide Inorganic materials 0.000 abstract 1
- 238000004140 cleaning Methods 0.000 abstract 1
- 150000001469 hydantoins Chemical class 0.000 abstract 1
- 239000002244 precipitate Substances 0.000 abstract 1
- 229940024606 amino acid Drugs 0.000 description 35
- HNDVDQJCIGZPNO-UHFFFAOYSA-N Histidine Chemical compound OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 16
- 150000001413 amino acids Chemical class 0.000 description 14
- 238000001816 cooling Methods 0.000 description 13
- 239000012452 mother liquor Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 8
- 239000000920 calcium hydroxide Substances 0.000 description 8
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 238000003756 stirring Methods 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- AYFVYJQAPQTCCC-UHFFFAOYSA-N THREONINE Chemical compound CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- MEPLDDAONLVHEF-UHFFFAOYSA-M benzyl(triethyl)azanium;hydrogen sulfate Chemical compound OS([O-])(=O)=O.CC[N+](CC)(CC)CC1=CC=CC=C1 MEPLDDAONLVHEF-UHFFFAOYSA-M 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 3
- 239000000347 magnesium hydroxide Substances 0.000 description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012264 purified product Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- BOYRGCUYTXBPQH-UHFFFAOYSA-N 2-amino-3-hydroxypropanenitrile Chemical compound OCC(N)C#N BOYRGCUYTXBPQH-UHFFFAOYSA-N 0.000 description 2
- MWLKEJXYXYRWIH-UHFFFAOYSA-N 2-amino-4-methylsulfanylbutanenitrile Chemical compound CSCCC(N)C#N MWLKEJXYXYRWIH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- CNXHRBZWXVQQAI-UHFFFAOYSA-N NC(C(=O)[O-])CCP(=O)(OC)OO.[NH4+] Chemical compound NC(C(=O)[O-])CCP(=O)(OC)OO.[NH4+] CNXHRBZWXVQQAI-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 150000004716 alpha keto acids Chemical class 0.000 description 2
- YNTQKXBRXYIAHM-UHFFFAOYSA-N azanium;butanoate Chemical compound [NH4+].CCCC([O-])=O YNTQKXBRXYIAHM-UHFFFAOYSA-N 0.000 description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-N sodium;hydron;carbonate Chemical class [Na+].OC(O)=O UIIMBOGNXHQVGW-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004176 ammonification Methods 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 235000019728 animal nutrition Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- AJSHDAOMUKXVDC-UHFFFAOYSA-N butan-1-amine;sulfuric acid Chemical compound CCCC[NH3+].OS([O-])(=O)=O AJSHDAOMUKXVDC-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013495 cobalt Nutrition 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical group NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical class O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
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- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
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Abstract
The invention relates to a synthesis and purification method for an alpha-amino acid compound. The synthesis and purification method is characterized by comprising the following steps: (1) adding substituted alpha-amino nitrile or a substituted hydantoin-based compound into alkali M(OH)x or metal oxide MxO, adding water or an alcohol and water mixed solvent, and heating for reaction to obtain alpha-amino acid salt; (2) adding ammonium carbonate or ammonium bicarbonate or introducing carbon dioxide into the solution in the step (1), separating to obtain filter liquor and precipitates MxHyCO3, performing reduced pressure concentration on the filter liquor, and recrystallizing in an alcohol solvent to obtain the alpha-amino acid compound (I). The synthesis and purification method for the alpha-amino acid compound is simple, the yield and purity of the obtained alpha-amino acid compound are high; furthermore, recycling utilization and cleaning production of materials can be realized; the synthesis and purification method is especially suitable for synthesis of the alpha-amino acid compound with high water solubility.
Description
Technical field
The present invention relates to a kind of synthesis and purification process of a-amino acid compounds.
Background technology
Amino acid is the basic composition unit of biological function macro-molecular protein, is the base substance forming Animal nutrition desired protein.The amino carboxylic acid be connected on alpha-carbon is a-amino acid.A-amino acid compounds is widely used in the industries such as food, medicine, agricultural chemicals, daily use chemicals.Current amino acid whose primary synthetic methods mainly contains microbe fermentation method, chemical synthesis and enzyme process.Wherein chemical synthesis process mainly contains:
A) method that is amino and carboxyl is introduced
(1) Strecker method
In aldehyde, pass into ammonia or add ammonium salt, carrying out cyanogenation, the intermediate acid adding of generation or alkali are hydrolyzed, synthesis a-amino acid.During use, ammonia and prussic acid can be replaced by ammonium chloride and potassium cyanide, and during synthesis, majority of case does not carry out intermediate separation.
(2) Buchere method
This method is the improvement of Strecker method.With cyaniding alkali and volatile salt and aldehyde reaction, the method for Preparation of amino acid by the hydrolysis of intermediate glycolylurea more afterwards.Glycolylurea normally obtains a-amino acid by being hydrolyzed in acidity or alkaline environment.
(3) by the method for carbonylation reaction
Using eight carbonyl two cobalts as catalyzer, by aldehyde, acid amides and carbon monoxide in high pressure, pyroreaction, the method for synthesis N-acetylamino acid.N-acetylamino acid uses ethyl acetate and dioxan to make solvent usually, through hydrolysis a-amino acid.
B), amino is incorporated into the method for carboxylic acid
(1) ammonification of alpha-halogenated carboxylic acids
Alpha-halogenated carboxylic acids carries out reacting with excess of ammonia and synthesizes the method for a-amino acid in water or alcohol.This method is almost all applicable to the synthesis of aliphatic amino acid.If add volatile salt can increase yield.
(2) amino is introduced by reduction method
This is one and uses platinum, contact reduction alpha-ketoacids such as, nickel under the existence of ammonia, or uses sodium and alcohol to reduce alpha-ketoacid to synthesize the method for a-amino acid.This law can synthesize each seed amino acid.
(3) in double bond, amino method is introduced
By maleic acid ester or fumaric acid vinegar and ammonia compressive reaction, ammonia is combined in double bond, and forms Diketopiperazine derivative, and then under alkalescence the method for hydrolysis DL-bis-aspartic acid.
C) in aminocompound, introduce the method (method of amino-oxide group alcohol) of carboxyl
The amino of beta-alkamine is suitably protected, after methylol is oxidized to carboxyl, then the method for the synthesis a-amino acid that is hydrolyzed.The oxygenant used has potassium permanganate, potassium bichromate etc.The amino protecting agent used has the acyl group of benzoyl, phenyl-diformyl base etc.The salts such as vitriol also can make protecting group.
D). ethanamide propanedioic acid ester process
The active methylene of ethanamide malonic ester is easy to and the condensation of halo uncle alkane, and condenses hydrolysis then can synthesize a-amino acid.Normally make solvent with alcohol, under the molar sodium ethylate of equivalent exists, carry out condensation.Also have under the existence of sodium hydroxide, with what carry out in the nonactive solvents such as toluene.The hydrolysis of condenses refluxes with acid or alkali, but usually with acid hydrolysis as well.
The method of conventional synthesis a-amino acid, is hydrolyzed under strongly alkaline conditions, and the consumption of alkali is generally at 3 ~ 5eq, and utilize amino acid in the poorest principle of iso-electric point solvability, aftertreatment adds a large amount of acid and regulates amino acid whose isoelectric fractionation to obtain product.Not only use a large amount of soda acids in this process, form a large amount of abraum salts after neutralization, and be not all applicable to all amino acid, as water-soluble large amino acid, aftertreatment is difficult to separation and obtains highly purified product.
Summary of the invention
The object of the invention is to the defect overcoming prior art, a kind of synthesis and purification process of a-amino acid compounds are provided, especially to the Amino acid synthesis of good water solubility, the separation of the high yield of energy obtains the amino acid products of high-quality, and realizes recycle and the cleaner production of material.
To achieve these goals, the technical scheme taked of the present invention is as follows:
The synthesis of a-amino acid compounds and a purification process, it specifically comprises the steps:
(1) alpha-aminonitriles (II) replaced or the hydantoin-based compound (III) of replacement are being added alkali M (OH)
xor metal oxide M
xo, add in water or alcohol water mixed solvent, reacting by heating obtains alpha-amino group hydrochlorate;
(2) add volatile salt or bicarbonate of ammonia or pass into carbonic acid gas in the solution of step (1), be separated and obtain filtrate and precipitation M
xh
ycO
3, after carrying out concentrating under reduced pressure to filtrate, recrystallization in alcoholic solvent, obtains a-amino acid compounds (I), and reaction formula is shown in formula (1);
(1)
Wherein, R is selected from following substituting group:
Wherein,
R
1, R
2the straight chained alkyl being selected from H, C1-C6 independently or branched-chain alkyl.
N=1,2,3,4 or 5;
X=1 or 2;
Y=0 or 1;
M is selected from sodium, calcium or magnesium, when M is selected from calcium or magnesium, is adding alkali M (OH) in step (1)
xor metal oxide M
xwhile O, before or after add organic amine, ammonia or ammoniacal liquor.
Further improve as the present invention, described organic amine is selected from methylamine, dimethylamine, Trimethylamine 99, ethamine, diethylamine, triethylamine or propylamine, the concentration of described ammoniacal liquor is 3 ~ 30% or ammonia, 0.5 ~ 6 equivalent of hydantoin-based compound (III) that ammonia or amine consumption are the alpha-aminonitriles (II) that replaces of substrate or replace.
Further improve as the present invention, in described step (1), when M is selected from calcium or magnesium, step is also added with catalyzer in (1), described catalyzer be quaternary ammonium salt and season phosphine saline catalyst or the polyoxyethylene glycol of molecular weight 400 ~ 8000, quaternary ammonium salt and season phosphine saline catalyst be selected from tetraalkyl ammonium sulfate, tetraalkyl monoammonium sulfate, tetraalkyl ammonium phosphate, tetraalkyl primary ammonium phosphate, triethylbenzyl ammonium sulfate, tetra-alkyl ammonium chloride, triethyl benzyl ammonia chloride, and tetraalkyl sulfuric acid phosphine, tetraalkyl phosphoric acid phosphine, triethylbenzyl sulfuric acid phosphine, triethylbenzyl phosphonium chloride, described alkyl is selected from C
1~ C
16chain hydrocarbon, described catalyst levels is 0.5 ~ 10% of substrate weight.
Further improve as the present invention, described alkali M (OH)
xor metal oxide M
xo adds 1 ~ 4 times that molar weight is the alpha-aminonitriles (II) replaced or hydantoin-based compound (III) molar weight replaced.
Further improve as the present invention, in described alcohol water mixed solvent, alcohol is selected from C
1~ C
4alcohol, particular methanol, ethanol, ethylene glycol, propyl alcohol, Virahol, butanols, isopropylcarbinol and the trimethyl carbinol, the ratio of alcohol and water is 1:10 ~ 1:5(w/w).
Further improve as the present invention, the temperature of reaction of described step (1) controls at 80 ~ 200 DEG C.
Further improve as the present invention, the reaction pressure of described step (1) is 0.1MPa ~ 10Mpa.
Further improve as the present invention, 0.5 ~ 3 equivalent of hydantoin-based compound (III) that the volatile salt of described step (2) or bicarbonate of ammonia or the amount passing into carbonic acid gas are the alpha-aminonitriles (II) that replaces of substrate or replace.
Further improve as the present invention, the method that the a-amino acid compounds alcoholic solvent obtained step (2) carries out recrystallization is purified, and alcoholic solvent is selected from methyl alcohol, one or more in ethanol and propyl alcohol.
Further improve as the present invention, comprise step (3) to gained precipitation M
xh
ycO
3can carry out recycling in step (1) by calcination, concrete grammar is as follows:
Work as M
xh
ycO
3during for calcium carbonate, reclaim CO by calcination
2and calcium oxide, CO
2recycling is in step (2) neutralization reaction, and calcium oxide is back to the hydrolysis reaction technique of step (1);
Work as M
xh
ycO
3during for magnesiumcarbonate, reclaim CO by calcination
2and magnesium oxide, CO
2recycling is in the neutralization reaction of step (2), and magnesium oxide is back to the hydrolysis reaction of step (1);
Work as M
xh
ycO
3during for sodium bicarbonate, use as weak base neutralizing acid.
Compared with prior art, the beneficial effect acquired by the present invention is as follows:
The alpha-aminonitriles of general replacement or the glycolylurea of replacement are hydrolyzed under strongly alkaline conditions, and recycling amino acid is in the poorest principle of iso-electric point solvability, and aftertreatment adds a large amount of acid and regulates amino acid whose isoelectric fractionation to obtain product.Not only use a large amount of soda acids in this process, form a large amount of abraum salts after neutralization, and be not all applicable to all amino acid, as water-soluble large amino acid, aftertreatment is difficult to separation and obtains highly purified product.
The present invention adopts sodium hydroxide, magnesium hydroxide, calcium hydroxide, and its corresponding oxide compound etc., the glycolylurea compound of the alpha-aminonitriles that hydrolysis replaces or replacement obtains alpha-amino group hydrochlorate.Utilize M
xh
ycO
3the principle of poorly water-soluble, is first separated removing inorganic salt.Be separated in the method for carrying out recrystallization with solvent and obtain highly purified product.
Adopt sodium hydroxide hydrolysis alpha-aminonitriles or glycolylurea compound to obtain a-amino acid sodium, then pass into carbonic acid gas, the sodium bicarbonate of generation, solubleness is less, and especially in the presence of an alcohol, the solubleness of sodium bicarbonate is less, can remove by the mode of filtering.The sodium bicarbonate generated can be widely used in neutralizing acid.
Adopt calcium hydroxide or magnesium hydroxide hydrolysis alpha-aminonitriles or glycolylurea compound to obtain a-amino acid calcium salt or magnesium salts, then when passing into carbonic acid gas or add carbonate, the calcium carbonate of generation or magnesiumcarbonate precipitation, be separated by the mode of filtering.The calcium carbonate generated or magnesiumcarbonate obtain CO through calcination
2with calcium oxide or or magnesium oxide, CO
2realize cycling and reutilization, calcium oxide or magnesium oxide capable of circulation for hydrolysis reaction.Whole technique achieves the recycle of main raw material, reaches cleaner production.
The present invention's reaction can be carried out having under catalyzer or catalyst-free condition, used catalyst be quaternary ammonium salt and season phosphine saline catalyst or the polyoxyethylene glycol of molecular weight 400 ~ 8000, adding of catalyzer, improve speed and the yield of reaction, reaction can be made to carry out smoothly, and obtain comparatively ideal yield.
The inventive method is simple, and the a-amino acid compounds yield obtained is high, and purity is high, can realize recycle and the cleaner production of material simultaneously, and the inventive method is especially applicable to the synthesis of water-soluble large a-amino acid compounds.
Embodiment
Below in conjunction with specific embodiment, detailed further describing is carried out to the present invention.
The synthesis of case study on implementation 1:2-amino-4-methylmercapto butyric acid
2-amino-4-methylthio butanenitrile 130g(1mol is added in 1L autoclave), add 68g 25% ammoniacal liquor and calcium oxide 56g(1mol), 4-butyl ammonium hydrogen sulfate 2g, water 500g, is heated to 180-190
oc, pressure 2., 5 ~ 3.0MPa, reaction 5h, is cooled to room temperature, passes into carbonic acid gas to pH=8 under stirring, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2-amino-4-methylmercapto butyric acid 118.3g, purity 96%, yield 79.4%.
Case study on implementation 2:2-amino-3-(4-imidazolyl) propionic acid synthesize
5-[(4-imidazolyl) methyl] glycolylurea 180g(1mol is added in 1L autoclave), add 68g 25% ammoniacal liquor and calcium hydroxide 110g(1.5mol), water 500g, is heated to 160-170
oc, pressure 1.5 ~ 2.0MPa, reaction 8h, is cooled to room temperature, passes into carbonic acid gas to pH=8 under stirring, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2-amino-3-(4-imidazolyl) propionic acid 124.2g, purity 96%, yield 80.1%.
Case study on implementation 3:2-amino-3-(4-imidazolyl) propionic acid synthesize
5-[(4-imidazolyl) methyl] glycolylurea 180g(1mol is added in 1L autoclave), add 68g 25% ammoniacal liquor and calcium hydroxide 110g(1.5mol), sulfuric acid triethylbenzyl ammonium 3g, water 500g, is heated to 160-170
oc, pressure 1.5 ~ 2.0MPa, reaction 3h, is down to room temperature, passes into carbonic acid gas to pH=8, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2-amino-3-(4-imidazolyl) propionic acid 134.5g, purity 96%, yield 86.8%.
Case study on implementation 4:2-amino-3-(4-imidazolyl) propionic acid synthesize
5-[(4-imidazolyl) methyl] glycolylurea 180g(1mol is added in 1L autoclave), add 34g 25% ammoniacal liquor and calcium hydroxide 110g(1.5mol), water 500g, is heated to 160-170
oc, pressure 1.5 ~ 2.0MPa, reaction 8h, is down to room temperature, passes into carbonic acid gas to pH=8, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2-amino-3-(4-imidazolyl) propionic acid 121.3g, purity 96%, yield 78.3%.
The synthesis of case study on implementation 5:2-amino-3-hydroxybutyrate
5-(1-hydroxyethyl is added in 1L autoclave) glycolylurea 144g(1mol), add 68g 25% ammoniacal liquor and calcium hydroxide 110g(1.5mol) and, water 500g, propyl carbinol 50mL, is heated to 160-170
oc, pressure 1.5 ~ 2.0MPa, reaction 4h, is down to room temperature, passes into carbonic acid gas to pH=8, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, filter cake vacuum 120
oc is dry, and 4h obtains 2 amino 3 hydroxybutyric acid 106.4g, purity 96%, yield 89.4%.
The synthesis of case study on implementation 6:2-amino-3-hydroxy-propionic acid
2-amino-3-hydroxypropionitrile 86g(1mol is added in 1L autoclave), add 136g 25% ammoniacal liquor and calcium hydroxide 110g(1.5mol), sulfuric acid triethylbenzyl ammonium 3g, water 500g, is heated to 180-190
oc, pressure 2.5 ~ 3.0MPa, reaction 4h, is down to 40-50
oc, adds bicarbonate of ammonia 118g(1.5mol), stir 1h, filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains L-Serine 92.3g, purity 96%, yield 87.9%.
The synthesis of case study on implementation 7:2-amino-3-hydroxy-propionic acid
2-amino-3-hydroxypropionitrile 86g(1mol is added in 1L autoclave), add 136g 25% ammoniacal liquor and magnesium hydroxide 87g(1.5mol), sulfuric acid triethylbenzyl ammonium 4g, water 500g, is heated to temperature 170-180
oc, pressure 2.0 ~ 2.5MPa, reaction 3h, is down to 40-50
oc, adds volatile salt 144g(1.5mol), stir 1h, filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, filter cake vacuum 120
oc is dry, and 4h obtains L-Serine 91.1g, purity 96%, yield 86.8%.
The synthesis of case study on implementation 8:2-amino-4-[hydroxyl (methyl) phosphono] butyric acid ammonium
2-amino-4-[oxyethyl group (methyl) phosphono] butyronitrile 190g(1mol is added in 1L autoclave), 25% ammonia soln 204g, adds calcium oxide 67g(1.2mol), tetrabutylammonium sulfate 4g, water 500g, is heated to 180-190
oc, pressure 2.5 ~ 3.0MPa, reaction 5h, is cooled to room temperature, passes into carbonic acid gas to pH=8, and filter, mother liquor evaporated under reduced pressure, adds 150g methanol eddy 2h, and cooling, has crystallization, filters, vacuum 120
oc is dry, and 4h obtains 2-amino-4-[hydroxyl (methyl) phosphono] butyric acid ammonium 169.8g, purity 96%, yield 85.8%.
The synthesis of case study on implementation 9:2-amino-4-[hydroxyl (methyl) phosphono] butyric acid ammonium
2-amino-4-[oxyethyl group (methyl) phosphono] butyronitrile 190g(1mol is added in 1L autoclave), 30% sodium hydroxide 533.3g(4mol), ethanol 30mL, is warming up to 160-170
oc, pressure 0.7 ~ 0.9MPa, reaction 5h, be cooled to room temperature, then pass into carbonic acid gas to pH=8, filter, mother liquor concentrating under reduced pressure, adds 150g methyl alcohol and 15g water, logical ammonia 34g, stir 6h, filter, filtrate reduced in volume, 150g methyl alcohol is warming up to backflow 2h again, and cooling, has crystallization, filter, vacuum 120
oc is dry, and 4h obtains 2-amino-4-[hydroxyl (methyl) phosphono] butyric acid ammonium 159.7g, purity 95.7%, yield 80.7%.
The synthesis of case study on implementation 10:2-amino-4-methylmercapto butyric acid
2-amino-4-methylthio butanenitrile 130g(1mol is added in 1L autoclave), pass into Monomethylamine 62g and calcium oxide 56g(1mol), 1g poly(oxyethylene glycol) 400, water 550g, is heated to 180-190
oc, pressure 2.5 ~ 3.0MPa, reaction 5h, is cooled to room temperature, passes into carbonic acid gas to pH=8 under stirring, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2-amino-4-methylmercapto butyric acid 105.8g, purity 96%.
Case study on implementation 11: the recycling of calcium carbonate
In case study on implementation 2,3,4 and 5, the calcium carbonate filtered out, calcination in Gas-making Furnace, reclaim carbonic acid gas, reusable edible is to case study on implementation 6 or for needing the reaction of carbonic acid gas.After calcination, residue calcium oxide, can be used for hydrolysis reaction, is applied to case study on implementation 1.
The synthesis of comparative example 1:2-amino-3-hydroxybutyrate
5-(1-hydroxyethyl is added in 1L autoclave) glycolylurea 144g(1mol), add 136g 25% ammoniacal liquor, sulfuric acid triethylbenzyl ammonium 3g, water 500g, is warming up to 160-170
oc, pressure 1.5 ~ 2.0MPa, reaction 5h, is down to room temperature, passes into carbonic acid gas to pH=8, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2 amino 3 hydroxybutyric acid 53.8g, purity 96%, yield 45%.
The synthesis of comparative example 2:2-amino-3-hydroxybutyrate
5-(1-hydroxyethyl is added in 1L autoclave) glycolylurea 144g(1mol), add calcium oxide 112g(2mol) and, sulfuric acid triethylbenzyl ammonium 3g, water 500g, is heated to 160-170
oc, pressure 0.7 ~ 0.9MPa, reaction 4h, is down to room temperature, passes into carbonic acid gas to pH=8, and filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, and cooling, has crystal to separate out.Filter, filter cake vacuum 120
oc is dry, and 4h obtains 2 amino 3 hydroxybutyric acid 65.7g, purity 96%, yield 55.2%.
Comparative example 3:2-amino-3-(4-imidazolyl) propionic acid synthesize
5-[(4-imidazolyl) methyl] glycolylurea 180g(1mol is added) in 1L four-hole bottle, add 68g 25% ammoniacal liquor and calcium hydroxide 110g(1.5mol), water 500g, stirring heating backflow 46h, is cooled to room temperature, logical carbonic acid gas is to Ph=8, filter, mother liquor concentrating under reduced pressure, resistates adds 150g methanol eddy 2h, cooling, has crystal to separate out.Filter, vacuum 120
oc is dry, and 4h obtains 2-amino-3-(4-imidazolyl) propionic acid 49.6g, purity 96%, yield 32.0%.
The above embodiment is only the preferred embodiments of the present invention, and and the feasible enforcement of non-invention exhaustive.For persons skilled in the art, to any apparent change done by it under the prerequisite not deviating from the principle of the invention and spirit, all should be contemplated as falling with within claims of the present invention.
Claims (10)
1. the synthesis of a-amino acid compounds and a purification process, is characterized in that comprising the steps:
(1) alpha-aminonitriles (II) replaced or the hydantoin-based compound (III) of replacement are being added alkali M (OH)
xor metal oxide M
xo, add in water or alcohol water mixed solvent, reacting by heating obtains alpha-amino group hydrochlorate;
(2) add volatile salt or bicarbonate of ammonia or pass into carbonic acid gas in the solution of step (1), be separated and obtain filtrate and precipitation M
xh
ycO
3, after carrying out concentrating under reduced pressure to filtrate, recrystallization in alcoholic solvent, obtains a-amino acid compounds (I), and reaction formula is shown in formula (1);
(1)
Wherein, R is selected from following substituting group:
Wherein,
R
1, R
2the straight chained alkyl being selected from H, C1-C6 independently or branched-chain alkyl;
N=1,2,3,4 or 5;
X=1 or 2;
Y=0 or 1;
M is selected from sodium, calcium or magnesium, when M is selected from calcium or magnesium, is adding alkali M (OH) in step (1)
xor metal oxide M
xwhile O, before or after add organic amine, ammonia or ammoniacal liquor.
2. the synthesis of a kind of a-amino acid compounds according to claim 1 and purification process, it is characterized in that: described organic amine is selected from methylamine, dimethylamine, Trimethylamine 99, ethamine, diethylamine, triethylamine or propylamine, the concentration of described ammoniacal liquor is 3 ~ 30% or ammonia, 0.5 ~ 6 equivalent of hydantoin-based compound (III) that ammonia or amine consumption are the alpha-aminonitriles (II) that replaces of substrate or replace.
3. the synthesis of a kind of a-amino acid compounds according to claim 1 and purification process, it is characterized in that: when M is selected from calcium or magnesium, step is also added with catalyzer in (1), described catalyzer be quaternary ammonium salt and season phosphine saline catalyst or the polyoxyethylene glycol of molecular weight 400 ~ 8000, quaternary ammonium salt and season phosphine saline catalyst be selected from tetraalkyl ammonium sulfate, tetraalkyl monoammonium sulfate, tetraalkyl ammonium phosphate, tetraalkyl primary ammonium phosphate, triethylbenzyl ammonium sulfate, tetra-alkyl ammonium chloride, triethyl benzyl ammonia chloride, and tetraalkyl sulfuric acid phosphine, tetraalkyl phosphoric acid phosphine, triethylbenzyl sulfuric acid phosphine, triethylbenzyl phosphonium chloride, described alkyl is selected from C
1~ C
16chain hydrocarbon, described catalyst levels is 0.5 ~ 10% of substrate weight.
4. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, is characterized in that: described alkali M (OH)
xor metal oxide M
xo adds 1 ~ 4 times that molar weight is the alpha-aminonitriles (II) replaced or hydantoin-based compound (III) molar weight replaced.
5. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, is characterized in that: in described alcohol water mixed solvent, alcohol is selected from C
1~ C
4alcohol, particular methanol, ethanol, ethylene glycol, propyl alcohol, Virahol, butanols, isopropylcarbinol or the trimethyl carbinol, the ratio of alcohol and water is 1:20 ~ 1:5(w/w).
6. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, is characterized in that: the temperature of reaction of described step (1) controls at 80 ~ 200 DEG C.
7. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, is characterized in that: the reaction pressure of described step (1) is 0.1MPa ~ 10Mpa.
8. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, is characterized in that: 0.5 ~ 3 equivalent of hydantoin-based compound (III) that the volatile salt of described step (2) or bicarbonate of ammonia or the amount passing into carbonic acid gas are the alpha-aminonitriles (II) that replaces of substrate or replace.
9. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, it is characterized in that: the method that the a-amino acid compounds alcoholic solvent obtained step (2) carries out recrystallization is purified, alcoholic solvent is selected from methyl alcohol, in ethanol and propyl alcohol one or both and more than.
10. the synthesis of a kind of a-amino acid compounds according to any one of claim 1-3 and purification process, is characterized in that: comprise step (3) to gained precipitation M
xh
ycO
3can carry out recycling in step (1) by calcination, concrete grammar is as follows:
Work as M
xh
ycO
3during for calcium carbonate, reclaim CO by calcination
2and calcium oxide, CO
2recycling is in step (2) neutralization reaction, and calcium oxide is back to the hydrolysis reaction technique of step (1);
Work as M
xh
ycO
3during for magnesiumcarbonate, reclaim CO by calcination
2and magnesium oxide, CO
2recycling is in the neutralization reaction of step (2), and magnesium oxide is back to the hydrolysis reaction of step (1);
Work as M
xh
ycO
3during for sodium bicarbonate, use as weak base neutralizing acid.
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