CN104892521B - 一种α-氨基酸类化合物的合成及纯化方法 - Google Patents
一种α-氨基酸类化合物的合成及纯化方法 Download PDFInfo
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- CN104892521B CN104892521B CN201510113479.4A CN201510113479A CN104892521B CN 104892521 B CN104892521 B CN 104892521B CN 201510113479 A CN201510113479 A CN 201510113479A CN 104892521 B CN104892521 B CN 104892521B
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- ammonium
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- acid compounds
- amino
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- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 34
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 32
- 150000001875 compounds Chemical class 0.000 title claims abstract description 25
- 238000000746 purification Methods 0.000 title claims abstract description 10
- 239000002253 acid Substances 0.000 title claims description 30
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000000034 method Methods 0.000 claims abstract description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 239000001099 ammonium carbonate Substances 0.000 claims abstract description 14
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 229910015955 MxHy Inorganic materials 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 10
- 235000012501 ammonium carbonate Nutrition 0.000 claims abstract description 8
- 229940091173 hydantoin Drugs 0.000 claims abstract description 8
- 230000001476 alcoholic effect Effects 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 7
- 229910044991 metal oxide Inorganic materials 0.000 claims abstract description 7
- 150000004706 metal oxides Chemical class 0.000 claims abstract description 7
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims abstract description 6
- 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 group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 53
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 30
- 229910021529 ammonia Inorganic materials 0.000 claims description 17
- 239000003054 catalyst Substances 0.000 claims description 16
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 13
- 239000000908 ammonium hydroxide Substances 0.000 claims description 13
- 230000007062 hydrolysis Effects 0.000 claims description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims description 13
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 10
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 10
- 239000000292 calcium oxide Substances 0.000 claims description 10
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 9
- 238000001354 calcination Methods 0.000 claims description 9
- 239000011575 calcium Substances 0.000 claims description 9
- 229910052791 calcium Inorganic materials 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 230000008859 change Effects 0.000 claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 238000004064 recycling Methods 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 5
- 239000011777 magnesium Chemical group 0.000 claims description 5
- 229910052749 magnesium Chemical group 0.000 claims description 5
- 239000000395 magnesium oxide Substances 0.000 claims description 5
- 238000006386 neutralization reaction Methods 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 150000003242 quaternary ammonium salts Chemical group 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
- 150000001469 hydantoins Chemical class 0.000 claims description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- 150000004714 phosphonium salts Chemical class 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- 235000019270 ammonium chloride Nutrition 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 3
- 239000001095 magnesium carbonate Substances 0.000 claims description 3
- 229910000021 magnesium carbonate Inorganic materials 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
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-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
- 150000001335 aliphatic alkanes Chemical class 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
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 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
- 239000002244 precipitate Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- IBIRZFNPWYRWOG-UHFFFAOYSA-N phosphane;phosphoric acid Chemical compound P.OP(O)(O)=O IBIRZFNPWYRWOG-UHFFFAOYSA-N 0.000 claims 1
- -1 α amino acid compounds Chemical class 0.000 abstract description 11
- 238000001556 precipitation Methods 0.000 abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 3
- 235000008206 alpha-amino acids Nutrition 0.000 abstract 4
- 125000005219 aminonitrile group Chemical group 0.000 abstract 1
- 238000001914 filtration Methods 0.000 description 28
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 23
- 229960004424 carbon dioxide Drugs 0.000 description 17
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 16
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 14
- 206010013786 Dry skin Diseases 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 238000001035 drying Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- AYFVYJQAPQTCCC-UHFFFAOYSA-N THREONINE Chemical compound CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 12
- 239000012452 mother liquor Substances 0.000 description 12
- 239000013078 crystal Substances 0.000 description 10
- 230000006872 improvement Effects 0.000 description 9
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
- 235000019260 propionic acid Nutrition 0.000 description 8
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 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 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 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 4
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 4
- 239000000920 calcium hydroxide Substances 0.000 description 4
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 4
- FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical class CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 4
- 238000012805 post-processing Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 229960001153 serine Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000010792 warming 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 compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-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
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization 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
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
- 229910002090 carbon oxide Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 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
- 238000010992 reflux Methods 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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004215 Carbon black (E152) Substances 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
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- YPNPLCUQNNKQBJ-UHFFFAOYSA-N acetamide;propanedioic acid Chemical compound CC(N)=O.OC(=O)CC(O)=O YPNPLCUQNNKQBJ-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
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- 235000019728 animal nutrition Nutrition 0.000 description 1
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- 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
- XNEYCQMMVLAXTN-UHFFFAOYSA-N carbonic acid;magnesium Chemical compound [Mg].OC(O)=O XNEYCQMMVLAXTN-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- QDYLMAYUEZBUFO-UHFFFAOYSA-N cetalkonium chloride Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 QDYLMAYUEZBUFO-UHFFFAOYSA-N 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
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- 230000001351 cycling effect Effects 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- SEGLCEQVOFDUPX-UHFFFAOYSA-N di-(2-ethylhexyl)phosphoric acid Chemical compound CCCCC(CC)COP(O)(=O)OCC(CC)CCCC SEGLCEQVOFDUPX-UHFFFAOYSA-N 0.000 description 1
- 150000002012 dioxanes Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
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- 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
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 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
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 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
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- 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
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Abstract
本发明涉及一种α‑氨基酸类化合物的合成及纯化方法,其特征在于包括如下步骤:(1)将取代的α‑氨基腈或取代的海因类化合物在加入碱M(OH)x或金属氧化物MxO,加入水或醇水混合溶剂中,加热反应得到α‑氨基酸盐;(2)向步骤(1)的溶液中加入碳酸铵或碳酸氢铵或通入二氧化碳,分离得到滤液和沉淀MxHyCO3,对滤液进行减压浓缩后,在醇溶剂中重结晶,得到α‑氨基酸类化合物(I)。本发明方法简单,得到的α‑氨基酸类化合物收率高,纯度高,同时可实现物料的循环利用和清洁生产,本发明方法尤其适合水溶性大α‑氨基酸类化合物的合成。
Description
技术领域
本发明涉及一种α-氨基酸类化合物的合成及纯化方法。
背景技术
氨基酸是生物功能大分子蛋白质的基本组成单位,是构成动物营养所需蛋白质的基本物质。氨基连接在α-碳上的羧酸为α-氨基酸。α-氨基酸类化合物广泛应用于食品、医药、农药、日化等行业。目前氨基酸的主要合成方法主要有微生物发酵法、化学合成法和酶法。其中化学合成方法主要有:
a) 引入氨基和羧基的方法
(1)Strecker法
在醛中通入氨或加入铵盐,在进行氰化反应,生成的中间体加酸或碱进行水解,合成α-氨基酸。使用时氨和氢氰酸是能由氯化铵和***来代替,合成时大多数情况不进行中间体分离的。
(2) Buchere法
此法是Strecker法的改进。是以氰化碱和碳酸铵与醛反应,之后再将中间体海因水解而制备氨基酸的方法。海因通常是在酸性或碱性环境中通过水解而得到α-氨基酸。
(3)用羰基化反应的方法
以八羰二钴作为催化剂,由醛、酰胺和一氧化碳在高压、高温反应,合成N-乙酰氨基酸的方法。N-乙酰氨基酸通常使用乙酸乙酯和二恶烷作溶剂,经水解合成α-氨基酸。
b)、将氨基引入到羧酸的方法
(1)α-卤代羧酸的氨化
α-卤代羧酸在水或醇中与过量的氨进行反应而合成α-氨基酸的方法。此法几乎全部适合脂肪族氨基酸的合成。若添加碳酸铵会增大收率。
(2) 用还原法引入氨基
这是一个在氨的存在下,使用铂、把、镍等接触还原α-酮酸,或者使用钠和醇还原α-酮酸以合成α-氨基酸的方法。本法能合成各种氨基酸。
(3) 在双键中引入氨基的方法
将马来酸酯或富马酸醋与氨加压反应,使氨结合在双键上,而形成二酮哌嗪衍生物,然后再在碱性下水解合成DL-二天门冬氨酸的方法。
c)、在氨基化合物中引入羧基的方法(氧化氨基醇的方法)
将β-氨基醇的氨基加以适当保护,将羟甲基氧化为羧基后,再进行水解合成α-氨基酸的方法。使用的氧化剂有高锰酸钾、重铬酸钾等。使用的氨基保护剂有苯甲酰基、苯二甲酰基等的酰基。硫酸盐等盐类也能作保护基。
d). 乙酰胺丙二酸酯法
乙酰胺丙二酸酯的活性次甲基很容易和卤代伯烷缩合,缩合物水解则能合成α-氨基酸。通常是以醇作溶媒,在等量克分子的乙醇钠存在下进行缩合。也有在氢氧化钠的存在下,以甲苯等非活性溶媒中进行的。缩合物的水解是与酸或碱回流,但通常以酸水解为好。
传统合成α-氨基酸的方法,在强碱性条件下水解,碱的用量一般在3~5eq,利用氨基酸在等电点溶解性最差的原理,后处理加入大量的酸调节氨基酸的等电点分离得到产品。该过程中不仅使用大量的酸碱,中和后形成大量的废盐,而且不是对所有的氨基酸均适用,如水溶性大的氨基酸,后处理很难分离得到高纯度的产品。
发明内容
本发明的目的在于克服现有技术的缺陷,提供一种α-氨基酸类化合物的合成及纯化方法,尤其是对水溶性好的氨基酸合成,能高收率的分离得到高品质的氨基酸产品,并且实现物料的循环利用和清洁生产。
为了实现上述目的,本发明采取的技术方案如下:
一种α-氨基酸类化合物的合成及纯化方法,其具体包括如下步骤:
(1) 将取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)在加入碱M(OH)x或金属氧化物MxO,加入水或醇水混合溶剂中,加热反应得到α-氨基酸盐;
(2) 向步骤(1)的溶液中加入碳酸铵或碳酸氢铵或通入二氧化碳,分离得到滤液和沉淀MxHyCO3,对滤液进行减压浓缩后, 在醇溶剂中重结晶,得到α-氨基酸类化合物(I),反应式见式 (1);
(1)
其中,R选自如下取代基:
其中,
R1,R2分别独立的选自H、C1-C6的直链烷基或支链烷基。
n = 1 、2、3、4或5;
x = 1或2;
y = 0或1;
M选自钠、钙或镁,当M选自钙或镁时,步骤(1)中在加入碱M(OH)x或金属氧化物MxO的同时、之前或之后加入有机胺、氨气或氨水。
作为本发明进一步的改进,所述有机胺选自甲胺,二甲胺,三甲胺,乙胺, 二乙胺,三乙胺或丙胺,所述氨水的浓度为3~30%或氨气,氨或胺用量为底物取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)的0.5~6当量。
作为本发明进一步的改进,在所述步骤(1)中,当M选自钙或镁时,步骤(1)中还加有催化剂,所述催化剂为季铵盐类和季膦盐类催化剂或分子量400~8000的聚乙二醇,季铵盐类和季膦盐类催化剂选自四烷基硫酸铵、四烷基硫酸氢铵、四烷基磷酸铵、四烷基磷酸二氢铵、三乙基苄基硫酸铵、四烷基氯化铵、三乙基苄基氯化铵,以及四烷基硫酸膦、四烷基磷酸膦、三乙基苄基硫酸膦、三乙基苄基氯化膦,所述烷基选自C1~C16的链烃,所述催化剂用量为底物重量的0.5~10%。
作为本发明进一步的改进,所述碱M(OH)x或金属氧化物MxO的加入摩尔量为取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)摩尔量的1~4倍。
作为本发明进一步的改进,所述醇水混合溶剂中醇选自C1~C4的醇,优选甲醇、乙醇、乙二醇、丙醇、异丙醇、丁醇, 异丁醇和叔丁醇,醇和水的比例为1:10~1:5(w/w)。
作为本发明进一步的改进,所述步骤(1)的反应温度控制在80~200℃。
作为本发明进一步的改进,所述步骤(1)的反应压力为0.1MPa ~10Mpa。
作为本发明进一步的改进,所述步骤(2)的碳酸铵或碳酸氢铵或通入二氧化碳的量为底物取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)的0.5~3当量。
作为本发明进一步的改进,对步骤(2)得到的α-氨基酸类化合物用醇溶剂进行重结晶的方法进行提纯, 醇溶剂选自甲醇,乙醇和丙醇中的一种或两种以上。
作为本发明进一步的改进,包括步骤(3)对所得沉淀MxHyCO3通过灼烧可进行回收利用到步骤(1)中,具体方法如下:
当MxHyCO3为碳酸钙时,通过灼烧回收CO2和氧化钙,CO2循环再用于步骤(2)中和反应, 氧化钙回用于步骤(1)的水解反应工艺;
当MxHyCO3为碳酸镁时,通过灼烧回收CO2和氧化镁,CO2循环再用于步骤(2)的中和反应, 氧化镁回用于步骤(1)的水解反应;
当MxHyCO3为碳酸氢钠时,作为弱碱中和酸使用。
与现有技术相比,本发明所取得的有益效果如下:
一般取代的α-氨基腈或取代的海因在强碱性条件下水解,再利用氨基酸在等电点溶解性最差的原理,后处理加入大量的酸调节氨基酸的等电点分离得到产品。该过程中不仅使用大量的酸碱,中和后形成大量的废盐,而且不是对所有的氨基酸均适用,如水溶性大的氨基酸,后处理很难分离得到高纯度的产品。
本发明采用氢氧化钠,氢氧化镁、氢氧化钙,以及其相应的氧化物等,水解取代的α-氨基腈或取代的海因化合物得到α-氨基酸盐。利用MxHyCO3水溶性差的原理,先分离除去无机盐。在用溶媒进行重结晶的方法分离得到高纯度的产品。
采用氢氧化钠水解α-氨基腈或海因化合物得到α-氨基酸钠,再通入二氧化碳,生成的碳酸氢钠,溶解度较小,尤其在醇的存在下, 碳酸氢钠的溶解度更小, 可以用过滤的方式除去。生成的碳酸氢钠可以广泛用于中和酸。
采用氢氧化钙或氢氧化镁水解α-氨基腈或海因化合物得到α-氨基酸钙盐或镁盐,再通入二氧化碳或加入碳酸盐时,生成的碳酸钙或碳酸镁沉淀,用过滤的方式分离。生成的碳酸钙或碳酸镁经灼烧得到CO2和氧化钙或或氧化镁,CO2实现循环再利用, 氧化钙或氧化镁可循环用于水解反应。整个工艺实现了主要原料的循环利用,达到清洁生产。
本发明反应可在有催化剂或无催化剂条件下进行,所用催化剂为季铵盐类和季膦盐类催化剂或分子量400~8000的聚乙二醇,催化剂的加入,提高了反应的速度和收率,可使反应能顺利进行,并得到较理想的收率。
本发明方法简单,得到的α-氨基酸类化合物收率高,纯度高,同时可实现物料的循环利用和清洁生产,本发明方法尤其适合水溶性大α-氨基酸类化合物的合成。
具体实施方式
以下结合具体实施例对本发明进行进一步详细的叙述。
实施案例1: 2-氨基-4-甲硫基丁酸的合成
1L高压釜内加入2-氨基-4-甲硫基丁腈130g(1mol),加入68g 25%氨水和氧化钙56g(1mol),四丁基硫酸氢铵2g,水500g,加热至180-190oC,压力2.,5 ~3.0MPa,反应5h,降温至室温,搅拌下通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-4-甲硫基丁酸118.3g,纯度96%,收率79.4%。
实施案例2:2-氨基-3-(4-咪唑基)丙酸的合成
1L高压釜内加入5-[(4-咪唑基)甲基]海因180g(1mol),加入68g 25%氨水和氢氧化钙110g(1.5mol),水500g,加热至160-170oC,压力1.5~2.0MPa,反应8h,降温至室温,搅拌下通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-3-(4-咪唑基)丙酸124.2g,纯度96%,收率80.1%。
实施案例3:2-氨基-3-(4-咪唑基)丙酸的合成
1L高压釜内加入5-[(4-咪唑基)甲基]海因180g(1mol),加入68g 25%氨水和氢氧化钙110g(1.5mol),硫酸三乙基苄基铵3g,水500g,加热至160-170oC,压力1.5~2.0MPa, 反应3h,降至室温,通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-3-(4-咪唑基)丙酸134.5g,纯度96%,收率86.8%。
实施案例4:2-氨基-3-(4-咪唑基)丙酸的合成
1L高压釜内加入5-[(4-咪唑基)甲基]海因180g(1mol),加入34g 25%氨水和氢氧化钙110g(1.5mol),水500g,加热至160-170oC,压力1.5~2.0MPa,反应8h,降至室温,通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-3-(4-咪唑基)丙酸121.3g,纯度96%,收率78.3%。
实施案例5:2-氨基-3-羟基丁酸的合成
1L高压釜内加入5-(1-羟基乙基)海因144g(1mol),加入68g 25%氨水和氢氧化钙110g(1.5mol),水500g,正丁醇50mL,加热至160-170oC,压力1.5~2.0MPa,反应4h,降至室温,通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,滤饼真空120oC干燥4h得2-氨基-3-羟基丁酸106.4g,纯度96%,收率89.4%。
实施案例6:2-氨基-3-羟基丙酸的合成
1L高压釜内加入2-氨基-3-羟基丙腈86g(1mol),加入136g 25%氨水和氢氧化钙110g(1.5mol),硫酸三乙基苄基铵3g,水500g, 加热至180-190oC,压力2.5~3.0MPa,反应4h,降至40-50oC,加入碳酸氢铵118g(1.5mol),搅拌1h,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-3-羟基丙酸92.3g,纯度96%,收率87.9%。
实施案例7:2-氨基-3-羟基丙酸的合成
1L高压釜内加入2-氨基-3-羟基丙腈86g(1mol),加入136g 25%氨水和氢氧化镁87g(1.5mol),硫酸三乙基苄基铵4g,水500g,加热至温度170-180oC,压力2.0~2.5MPa,反应3h,降至40-50oC,加入碳酸铵144g(1.5mol),搅拌1h,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,滤饼真空120oC干燥4h得2-氨基-3-羟基丙酸91.1g,纯度96%,收率86.8%。
实施案例8:2-氨基-4-[羟基(甲基)膦酰基]丁酸铵的合成
1L高压釜内加入2-氨基-4-[乙氧基(甲基)膦酰基]丁腈190g(1mol),25%氨水溶液204g,加入氧化钙67g(1.2mol),硫酸四丁基铵4g,水500g,加热至180-190oC,压力2.5~3.0MPa,反应5h,降温至室温,通入二氧化碳至pH=8,过滤,母液减压蒸干, 加入150g甲醇回流2h,降温,有结晶析出,过滤,真空120oC干燥4h得2-氨基-4-[羟基(甲基)膦酰基]丁酸铵169.8g,纯度96%,收率85.8%。
实施案例9:2-氨基-4-[羟基(甲基)膦酰基]丁酸铵的合成
1L高压釜内加入2-氨基-4-[乙氧基(甲基)膦酰基]丁腈190g(1mol),30%氢氧化钠533.3g(4mol),乙醇30mL,升温至160-170oC,压力0.7~0.9MPa,反应5h,降温至室温,然后通入二氧化碳至pH=8,过滤,母液减压浓缩, 加入150g甲醇和15g水,通氨气34g,搅拌6h,过滤,滤液减压浓缩,再150g甲醇升温至回流2h,降温,有结晶析出,过滤,真空120oC干燥4h得2-氨基-4-[羟基(甲基)膦酰基]丁酸铵159.7g,纯度95.7%,收率80.7%。
实施案例10: 2-氨基-4-甲硫基丁酸的合成
1L高压釜内加入2-氨基-4-甲硫基丁腈130g(1mol),通入一甲胺62g和氧化钙56g(1mol),1g聚乙二醇400,水550g,加热至180-190oC,压力2.5~3.0MPa,反应5h,降温至室温,搅拌下通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-4-甲硫基丁酸105.8g,纯度96%。
实施案例11:碳酸钙的回收利用
实施案例2、3、4和5中, 过滤出的碳酸钙,在造气炉中灼烧,回收二氧化碳,可循环利用到实施案例6或用于需要二氧化碳的反应。灼烧后残留物氧化钙,可用于水解反应,应用于实施案例1。
对比例1:2-氨基-3-羟基丁酸的合成
1L高压釜内加入5-(1-羟基乙基)海因144g(1mol),加入136g 25%氨水,硫酸三乙基苄基铵3g,水500g,升温至160-170oC,压力1.5~2.0MPa,反应5h,降至室温,通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-3-羟基丁酸53.8g,纯度96%,收率45%。
对比例2:2-氨基-3-羟基丁酸的合成
1L高压釜内加入5-(1-羟基乙基)海因144g(1mol),加入氧化钙112g(2mol),硫酸三乙基苄基铵3g,水500g,加热至160-170oC, 压力0.7~0.9MPa,反应4h,降至室温,通入二氧化碳至pH=8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,滤饼真空120oC干燥4h得2-氨基-3-羟基丁酸65.7g,纯度96%,收率55.2%。
对比例3:2-氨基-3-(4-咪唑基)丙酸的合成
1L四口瓶内加入5-[(4-咪唑基)甲基]海因180g(1mol),加入68g 25%氨水和氢氧化钙110g(1.5mol),水500g,搅拌加热回流46h,降温至室温,通二氧化碳至Ph = 8,过滤,母液减压浓缩,残余物加入150g甲醇回流2h,降温,有晶体析出。过滤,真空120oC干燥4h得2-氨基-3-(4-咪唑基)丙酸49.6g,纯度96%,收率32.0%。
以上所述实施方式仅为本发明的优选实施例,而并非本发明可行实施的穷举。对于本领域一般技术人员而言,在不背离本发明原理和精神的前提下对其所作出的任何显而易见的改动,都应当被认为包含在本发明的权利要求保护范围之内。
Claims (5)
1.一种α-氨基酸类化合物的合成及纯化方法,其特征在于包括如下步骤:
(1) 向取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)中加入碱M(OH)x或金属氧化物MxO,加入水或醇水混合溶剂,加热反应得到α-氨基酸盐;
(2) 向步骤(1)的溶液中加入碳酸铵或碳酸氢铵或通入二氧化碳,分离得到滤液和沉淀MxHyCO3,对滤液进行减压浓缩后,在醇溶剂中重结晶,得到α-氨基酸类化合物(I),反应式见式 (1);
说明: http://pic.cnipr.com/XmlData/fm/20150909/201510113479.4/DEST_PATH_IMAGE001.GIF(1)
其中,R选自如下取代基:
说明: http://pic.cnipr.com/XmlData/fm/20150909/201510113479.4/DEST_PATH_IMAGE002.GIF
其中,
R1,R2分别独立的选自H、C1~C6的直链烷基或支链烷基;
n = 1 、2、3、4或5;
x = 1或2;
y = 0或1;
M选自钙或镁,步骤(1)中在加入碱M(OH)x或金属氧化物MxO的同时、之前或之后加入有机胺、氨气或氨水;
所述有机胺选自甲胺,二甲胺,三甲胺,乙胺, 二乙胺,三乙胺或丙胺,所述氨水的质量浓度为3~30%或氨气,氨或胺用量为底物取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)的0.5~6当量;
所述碱M(OH)x或金属氧化物MxO的加入摩尔量为取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)摩尔量的1~4倍;
所述步骤(1)的反应温度控制在80~200℃;
所述步骤(1)的反应压力为0.1MPa ~10MPa;
所述步骤(2)的碳酸铵或碳酸氢铵或通入二氧化碳的量为底物取代的α-氨基腈(Ⅱ)或取代的海因类化合物(Ⅲ)的0.5~3当量。
2.根据权利要求1所述的一种α-氨基酸类化合物的合成及纯化方法,其特征在于:步骤(1)中还加有催化剂,所述催化剂为季铵盐类和季膦盐类催化剂或分子量400~8000的聚乙二醇,季铵盐类和季膦盐类催化剂选自四烷基硫酸铵、四烷基硫酸氢铵、四烷基磷酸铵、四烷基磷酸二氢铵、三乙基苄基硫酸铵、四烷基氯化铵、三乙基苄基氯化铵,以及四烷基硫酸膦、四烷基磷酸膦、三乙基苄基硫酸膦、三乙基苄基氯化膦,所述烷基选自C1~C16的链状烷基,所述催化剂用量为底物重量的0.5~10%。
3.根据权利要求1所述的一种α-氨基酸类化合物的合成及纯化方法,其特征在于:所述醇水混合溶剂中醇选自C1~C4的醇,醇和水的比例为1:20~1:5(w/w)。
4.根据权利要求1所述的一种α-氨基酸类化合物的合成及纯化方法,其特征在于:对步骤(2)得到的α-氨基酸类化合物用醇溶剂进行重结晶的方法进行提纯, 醇溶剂选自甲醇,乙醇和丙醇中的一种或两种及以上。
5.根据权利要求1所述的一种α-氨基酸类化合物的合成及纯化方法,其特征在于:所得沉淀MxHyCO3通过灼烧可进行回收利用,具体方法如下:
当MxHyCO3为碳酸钙时,通过灼烧回收CO2和氧化钙,CO2循环再用于步骤(2)中和反应,氧化钙回用于步骤(1)的水解反应;
当MxHyCO3为碳酸镁时,通过灼烧回收CO2和氧化镁,CO2循环再用于步骤(2)的中和反应,氧化镁回用于步骤(1)的水解反应。
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