JP5143838B2 - Method for producing α-hydroxy acid from α-hydroxy acid ammonium salt - Google Patents
Method for producing α-hydroxy acid from α-hydroxy acid ammonium salt Download PDFInfo
- Publication number
- JP5143838B2 JP5143838B2 JP2009524401A JP2009524401A JP5143838B2 JP 5143838 B2 JP5143838 B2 JP 5143838B2 JP 2009524401 A JP2009524401 A JP 2009524401A JP 2009524401 A JP2009524401 A JP 2009524401A JP 5143838 B2 JP5143838 B2 JP 5143838B2
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- Prior art keywords
- group
- hydroxy acid
- aqueous solvent
- thin film
- film evaporator
- Prior art date
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- 229940061720 alpha hydroxy acid Drugs 0.000 title claims description 21
- 150000001280 alpha hydroxy acids Chemical class 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- -1 α-hydroxy acid ammonium salt Chemical class 0.000 title description 122
- 239000010409 thin film Substances 0.000 claims description 23
- 239000003125 aqueous solvent Substances 0.000 claims description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 20
- 238000010438 heat treatment Methods 0.000 claims description 12
- 229910021529 ammonia Inorganic materials 0.000 claims description 10
- 238000001704 evaporation Methods 0.000 claims description 10
- 230000008020 evaporation Effects 0.000 claims description 10
- 239000011261 inert gas Substances 0.000 claims description 10
- 239000007789 gas Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 238000012546 transfer Methods 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000001261 hydroxy acids Chemical class 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 16
- 125000003277 amino group Chemical group 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 4
- 125000004317 1,3,5-triazin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=N1 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 3
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 2
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 2
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 2
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000005137 alkenylsulfonyl group Chemical group 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000004664 haloalkylsulfonylamino group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 2
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 description 2
- 125000004500 isothiazol-4-yl group Chemical group S1N=CC(=C1)* 0.000 description 2
- 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 description 2
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 2
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 2
- 125000006606 n-butoxy group Chemical group 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 2
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 2
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 description 1
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 description 1
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 1
- 125000006083 1-bromoethyl group Chemical group 0.000 description 1
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- OWRDCCHAWIMXAB-UHFFFAOYSA-N 2-hydroxy-2-pyridin-2-ylacetic acid Chemical compound OC(=O)C(O)C1=CC=CC=N1 OWRDCCHAWIMXAB-UHFFFAOYSA-N 0.000 description 1
- VBWPSWWDYVWZKA-UHFFFAOYSA-N 2-hydroxybut-3-enoic acid Chemical compound C=CC(O)C(O)=O VBWPSWWDYVWZKA-UHFFFAOYSA-N 0.000 description 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000186063 Arthrobacter Species 0.000 description 1
- 241000186073 Arthrobacter sp. Species 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 102000016901 Glutamate dehydrogenase Human genes 0.000 description 1
- IGRURXZWJCSNKU-UHFFFAOYSA-N Isopropenylacetic acid Chemical compound CC(=C)CC(O)=O IGRURXZWJCSNKU-UHFFFAOYSA-N 0.000 description 1
- NGEWQZIDQIYUNV-UHFFFAOYSA-N L-valinic acid Natural products CC(C)C(O)C(O)=O NGEWQZIDQIYUNV-UHFFFAOYSA-N 0.000 description 1
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000005108 alkenylthio group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 125000005109 alkynylthio group Chemical group 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- NWCHELUCVWSRRS-UHFFFAOYSA-N atrolactic acid Chemical compound OC(=O)C(O)(C)C1=CC=CC=C1 NWCHELUCVWSRRS-UHFFFAOYSA-N 0.000 description 1
- XOLXLUGLZJFTDJ-UHFFFAOYSA-N azanium;2-hydroxypentanethioate Chemical compound [NH4+].CCCC(O)C([O-])=S XOLXLUGLZJFTDJ-UHFFFAOYSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000006015 bromomethoxy group Chemical group 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
- 125000004783 dichloromethoxy group Chemical group ClC(O*)Cl 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000909 electrodialysis Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
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- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 125000000177 propargylthio group Chemical group [H]C#CC([H])([H])S* 0.000 description 1
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、種々の医薬・農薬等の合成原料として工業的に重要であり、また、ある種のものは食品添加物や飼料添加剤として利用されているα−ヒドロキシ酸の製造法に関する。 The present invention is industrially important as a synthetic raw material for various pharmaceuticals, agricultural chemicals, and the like, and certain types relate to a method for producing an α-hydroxy acid which is used as a food additive or a feed additive.
微生物を用いる方法等により得られたα−ヒドロキシ酸アンモニウム塩からアンモニアを回収し、遊離のα−ヒドロキシ酸を得る方法としては、例えば、電解透析による方法（特許文献１、２を参照）、α−ヒドロキシ酸アンモニウム塩を無溶媒又は有機溶媒中で加熱してアンモニアを回収し、続いて水を添加し加熱して一部生成したオリゴマー類を加水分解してα−ヒドロキシ酸を製造する方法（特許文献３を参照）等が知られている。また、α−ヒドロキシ酸アンモニウム塩を含む水性溶媒溶液を、加圧加熱することにより、アンモニアを遊離させ、水性溶媒とともに蒸発させる方法が知られている。（特許文献４を参照） Examples of a method for recovering ammonia from α-hydroxy acid ammonium salt obtained by a method using a microorganism and obtaining free α-hydroxy acid include electrodialysis (see Patent Documents 1 and 2), α -Method for producing an α-hydroxy acid by heating ammonium hydroxy acid salt in a solvent-free or organic solvent to recover ammonia, followed by addition of water and heating to hydrolyze a part of the produced oligomers ( (See Patent Document 3). In addition, a method is known in which ammonia is liberated by heating an aqueous solvent solution containing an α-hydroxy acid ammonium salt under pressure and evaporated together with the aqueous solvent. (See Patent Document 4)
しかし、いずれの方法も、エネルギーコストが高く、工業的には効率のいい反応とはいえなかった。また、特許文献４には、薄膜式蒸発装置を使用できることも記載されているが、その具体的な条件等の記載はない。
本発明は、エネルギーコストが小さく、工業的に効率のよいα−ヒドロキシ酸アンモニウム塩からアンモニアを回収し、遊離のα−ヒドロキシ酸を得る方法を提供することを目的とする。However, both methods have high energy costs and are not industrially efficient reactions. Patent Document 4 also describes that a thin film evaporator can be used, but there is no description of specific conditions and the like.
An object of the present invention is to provide a method for recovering ammonia from an α-hydroxy acid ammonium salt that is low in energy cost and industrially efficient to obtain free α-hydroxy acid.
本発明者らは、上記課題を解決すべく鋭意検討した結果、薄膜蒸発装置を用い、さらに、添加する溶液に対して、不活性ガス又は空気を向流させることで、常圧又は減圧下に効率よくアンモニアを除去できることを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have used a thin film evaporation apparatus, and further caused an inert gas or air to flow countercurrently to the solution to be added, thereby reducing the pressure to normal pressure or reduced pressure. The inventors have found that ammonia can be efficiently removed, and have completed the present invention.
即ち本発明は、式（Ｉ）
ＲＣＨ（ＯＨ）ＣＯＯ−ＮＨ４ ＋ （Ｉ）
（式中、Ｒは水素原子、Ｃ１〜Ｃ６アルキル基、Ｃ２〜Ｃ６アルケニル基、Ｃ１〜Ｃ６アルコキシ基、アリール基、アリールオキシ基又は複素環基を表す。）で表されるα−ヒドロキシ酸アンモニウム塩の水性溶媒溶液を、薄膜蒸発装置を用いて加熱を行いながら不活性ガス又は空気を前記水性溶媒溶液と向流させることでアンモニアを遊離させ、水性溶媒とともに蒸発させることを特徴とする式（ＩＩ）
ＲＣＨ（ＯＨ）ＣＯＯＨ （ＩＩ）
（式中、Ｒは前記と同じ意味を表す。）で表されるα−ヒドロキシ酸の製造方法に関し、薄膜蒸発装置は撹拌式薄膜蒸発装置であることが好ましく、また、竪型であることが好ましい。That is, the present invention provides a compound of formula (I)
RCH (OH) COO - NH 4 + (I)
(In the formula, R represents a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, an aryl group, an aryloxy group, or a heterocyclic group). An aqueous solvent solution of a salt is heated by using a thin film evaporator, and ammonia is liberated by countercurrent of the inert gas or air to the aqueous solvent solution, and the salt is evaporated together with the aqueous solvent. II)
RCH (OH) COOH (II)
(Wherein, R represents the same meaning as described above), the thin film evaporation device is preferably a stirring thin film evaporation device, and is a saddle type. preferable.
また、前記不活性ガス又は空気の流量が、薄膜蒸発装置の伝熱部分の塔断面積に対するガス空塔速度を０．０１ｍ／ｓ以上とするのが好ましく、前記不活性ガス又は空気の流量が、薄膜蒸発装置に添加する前記水性溶媒溶液量１ｇあたり１．６Ｌ以上であるのが好ましく、さらに前記不活性ガス又は空気の流量（Ｌ／分）が、薄膜蒸発装置に添加する前記水性溶媒溶液量（ｇ／分）よりも大きいのが好ましい。 Further, the flow rate of the inert gas or air is preferably 0.01 m / s or more with respect to the tower cross-sectional area of the heat transfer portion of the thin-film evaporator, and the flow rate of the inert gas or air is The aqueous solvent solution added to the thin film evaporator is preferably 1.6 L or more per gram of the aqueous solvent solution, and the flow rate (L / min) of the inert gas or air is further added to the thin film evaporator. It is preferably greater than the amount (g / min).
また、加熱温度が、１５０〜１７５℃の範囲であるのが好ましく、前記水性溶媒溶液を加熱温度以下に加熱しておくことが好ましい。 Moreover, it is preferable that heating temperature is the range of 150-175 degreeC, and it is preferable to heat the said aqueous solvent solution below heating temperature.
本発明で使用される式（Ｉ）で表される化合物中、Ｒとして具体的には、水素原子、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓ−ブチル基、イソブチル基、ｔ−ブチル基、ｎ−ヘキシル基、シクロプロピル基、シクロプロピルメチル基、シクロヘキシル基等のＣ１〜Ｃ６アルキル基、ビニル基、アリル基、３−ブテニル基、シクロブテニル基、シクロブテニルメチル基等のＣ２〜Ｃ６アルケニル基、メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｓ−ブトキシ基、ｔ−ブトキシ基、ｎ−ヘキシルオキシ基、シクロプロポキシ基、シクロヘキシルオキシ基等のＣ１〜Ｃ６アルコキシ基、フェニル基、１−ナフチル基、９−アントラニル基、ベンジル基、フェネチル基等のアリール基、フラン−２−イル基、フラン−３−イル基、チオフェン−２−イル基、チオフェン−３−イル基、ピロール−２−イル基、ピロール−３−イル基、オキサゾール−２−イル基、オキサゾール−４−イル基、オキサゾール−５−イル基、チアゾール−２−イル基、チアゾール−４−イル基、チアゾール−５−イル基、イソオキサゾール−３−イル基、イソオキサゾール−４−イル基、イソオキサゾール−５−イル基、イソチアゾール−３−イル基、イソチアゾール−４−イル基、イソチアゾール−５−イル基、イミダゾール−２−イル基、イミダゾール−４−イル基、イミダゾール−５−イル基、ピラゾール−３−イル基、ピラゾール−４−イル基、ピラゾール−５−イル基、１，３，４−オキサジアゾール−２−イル基、１，３，４−チアジアゾール−２−イル基、１，２，３−トリアゾール−４−イル基、１，２，４−トリアゾール−３−イル基、１，２，４−トリアゾール−５−イル基、ピリジン−２−イル基、ピリジン−３−イル基、ピリジン−４−イル基、ピリダジン−３−イル基、ピリダジン−４−イル基、ピラジン−２−イル基、ピリミジン−２−イル基、ピリミジン−４−イル基、ピリミジン−５−イル基、１，３，５−トリアジン−２−イル基、１，２，４−トリアジン−３−イル基、２−フルフリルメチル基、３−チエニルメチル基、１−メチル−３−ピラゾロメチル基、ピリジン−２−イル基、ピリジン−３−イル基、ピリジン−４−イル基、ピリダジン−３−イル基、ピリダジン−４−イル基、ピラジン−２−イル基、ピリミジン−２−イル基、ピリミジン−４−イル基、ピリミジン−５−イル基、１，３，５−トリアジン−２−イル基、１，２，４−トリアジン−３−イル基、２−ピリジルメチル基、３−ピリジルメチル基、６−クロル−３−ピリジルメチル基、２−ピリミジルメチル基、テトラヒドロフラン−２−イル基、テトラヒドラピラン−４−イル基、ピペリジン−３−イル基、ピロリジン−２−イル基、モルホリノ基、ピペリジノ基、Ｎ−メチルピペラジニル基、２−テトラヒドラフラニルメチル基、３−ピペラジルメチル基、Ｎ−メチル３−ピロリジルメチル基、モルホリノメチル基等の複素環基を具体的に例示することができる。 In the compound represented by the formula (I) used in the present invention, R is specifically a hydrogen atom, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, s-butyl group. , Isobutyl group, t-butyl group, n-hexyl group, cyclopropyl group, cyclopropylmethyl group, cyclohexyl group and other C1-C6 alkyl groups, vinyl group, allyl group, 3-butenyl group, cyclobutenyl group, cyclobutenyl C2-C6 alkenyl group such as methyl group, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, s-butoxy group, t-butoxy group, n-hexyloxy group, cyclopropoxy group, C1-C6 alkoxy group such as cyclohexyloxy group, phenyl group, 1-naphthyl group, 9-anthranyl group, benzyl group, phenethyl group and the like Group, furan-2-yl group, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyrrol-2-yl group, pyrrol-3-yl group, oxazol-2- Yl group, oxazol-4-yl group, oxazol-5-yl group, thiazol-2-yl group, thiazol-4-yl group, thiazol-5-yl group, isoxazol-3-yl group, isoxazole-4 -Yl group, isoxazol-5-yl group, isothiazol-3-yl group, isothiazol-4-yl group, isothiazol-5-yl group, imidazol-2-yl group, imidazol-4-yl group, Imidazol-5-yl group, pyrazol-3-yl group, pyrazol-4-yl group, pyrazol-5-yl group, 1,3,4-oxadiazol-2-yl group, 1,3, -Thiadiazol-2-yl group, 1,2,3-triazol-4-yl group, 1,2,4-triazol-3-yl group, 1,2,4-triazol-5-yl group, pyridine-2 -Yl group, pyridin-3-yl group, pyridin-4-yl group, pyridazin-3-yl group, pyridazin-4-yl group, pyrazin-2-yl group, pyrimidin-2-yl group, pyrimidine-4- Yl group, pyrimidin-5-yl group, 1,3,5-triazin-2-yl group, 1,2,4-triazin-3-yl group, 2-furfurylmethyl group, 3-thienylmethyl group, 1 -Methyl-3-pyrazolomethyl group, pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, pyridazin-3-yl group, pyridazin-4-yl group, pyrazin-2-yl group, Pyrimidin-2-yl group, Limidin-4-yl group, pyrimidin-5-yl group, 1,3,5-triazin-2-yl group, 1,2,4-triazin-3-yl group, 2-pyridylmethyl group, 3-pyridylmethyl Group, 6-chloro-3-pyridylmethyl group, 2-pyrimidylmethyl group, tetrahydrofuran-2-yl group, tetrahydrapyran-4-yl group, piperidin-3-yl group, pyrrolidin-2-yl group, morpholino group, Specific examples of heterocyclic groups such as piperidino group, N-methylpiperazinyl group, 2-tetrahydrafuranylmethyl group, 3-piperazylmethyl group, N-methyl-3-pyrrolidylmethyl group, morpholinomethyl group Can do.
これらの官能基は、化学的に許容される範囲で、置換基を有していてもよく、そのような置換基として具体的には、以下のような置換基を例示することができる。 These functional groups may have a substituent within a chemically acceptable range, and specific examples of such a substituent include the following substituents.
水酸基；チオール基；フッ素原子、塩素原子、臭素原子、ヨウ素原子等のハロゲン原子；シアノ基；ニトロ基；ホルミル基；アミノ基、メチルアミノ基、ベンジルアミノ基、アニリノ基、ジメチルアミノ基、ジエチルアミノ基、フェニルエチルアミノ基等の無置換又は置換アミノ基；メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、イソブチル基、ｔ−ブチル基、ｎ−ペンチル基、ｎ−ヘキシル基等のアルキル基（Ｃ１−６アルキル基が好ましい）；ビニル基、アリル基、２−メトキシ−エテニル基等のアルケニル基；エチニル基、１−プロピニル基、２−フェニルエチニル基、プロパルギル基等のアルキニル基；メトキシ基、エトキシ基、プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｓｅｃ−ブトキシ基、イソブトキシ基、ｔ−ブトキシ基等のアルコキシ基（Ｃ１−６アルコキシ基が好ましい）；ビニルオキシ基、アリルオキシ基等のアルケニルオキシ基；エチニルオキシ基、プロパルギルオキシ基等のアルキニルオキシ基；フェノキシ基、ベンジルオキシ基、２−ピリジルオキシ基等のアリールオキシ基；クロロメチル基、フルオロメチル基、ブロモメチル基、ジクロロメチル基、ジフルオロメチル基、ジブロモメチル基、トリクロロメチル基、トリフルオロメチル基、ブロモジフルオロメチル基、トルフルオロエチル基、１−クロロエチル基、２−クロロエチル基、１−ブロモエチル基、２−ブロモエチルペンタフルオロエチル基等のハロアルキル基（Ｃ１−６ハロアルキル基が好ましい）；フルオロメトキシ基、クロロメトキシ基、ブロモメトキシ基、ジフルオロメトキシ基、ジクロロメトキシ基、ジブロモメトキシ基、トリフルオロメトキシ基、トリクロロメトキシ基、トリブロモメトキシ基、トリフルオロエトキシ基、ペンタフルオロエトキシ基、ヘプタフルオロプロポキシ基等のハロアルコキシ基（Ｃ１−６ハロアルコキシ基が好ましい）；メチルチオカルボニル基、エチルチオカルボニル基、プロピルチオカルボニル基、イソプロピルチオカルボニル基、ブチルチオカルボニル基、イソブチルチオカルボニル基、ｓｅｃ−ブチルチカルボニル基、ｔ−ブチルチオカルボニル基等のアルキルチオカルボニル基（Ｃ１−６アルキルチオカルボニル基が好ましい）；メチルスルホニルアミノ基、エチルスルホニルアミノ基、プロピルスルホニルアミノ基、イソプロピルスルホニルアミノ基、ブチルスルホニルアミノ基、ｔ−ブチルスルホニルアミノ基等のアルキルスルホニルアミノ基（Ｃ１−６アルキルスルホニルアミノ基が好ましい）；フェニルスルホニルアミノ基、ピペラジニルスルホニルアミノ基等のアリールスルホニルアミノ基（Ｃ６−１２アリールスルホニルアミノ基が好ましい）；メチルカルボニルアミノ基、エチルカルボニルアミノ基、プロピルカルボニルアミノ基、イソプロピルカルボニルアミノ基等のアルキルカルボニルアミノ基（Ｃ１−６アルキルカルボニルアミノ基が好ましい）；メトキシカルボニルアミノ基、エトキシカルボニルアミノ基、プロポキシカルボニルアミノ基、イソプロポキシカルボニルアミノ基等のアルコキシカルボニルアミノ基（Ｃ１−６アルコキシカルボニルアミノ基が好ましい）；フルオロメチルスルホニルアミノ基、クロロメチルスルホニルアミノ基、ブロモメチルスルホニルアミノ基、ジフルオロメチルスルホニルアミノ基、ジクロロメチルスルホニルアミノ基、ジフルオロメチルスルホニルアミノ基、トリフルオロメチルスルホニルアミノ基、トリフルオロエチルスルホニルアミノ基、ペンタフルオロエチルスルホニルアミノ基等のハロアルキルスルホニルアミノ基（Ｃ１−６ハロアルキルスルホニルアミノ基が好ましい）；ビス（メチルスルホニル）アミノ基、ビス（エチルスルホニル）アミノ基、（メチルスルホニル）（エチルスルホニル）アミノ基、ビス（プロピルスルホニル）アミノ基、ビス（イソプロピルスルホニル）アミノ基、ビス（ブチルスルホニル）アミノ基、ビス（ｔ−ブチルスルホニル）アミノ基等のビス（アルキルスルホニル）アミノ基（ビス（Ｃ１−６アルキルスルホニル）アミノ基が好ましい）；ビス（フルオロメチルスルホニル）アミノ基、ビス（クロロメチルスルホニル）アミノ基、ビス（ブロモメチルスルホニル）アミノ基、ビス（ジフルオロメチルスルホニル）アミノ基、ビス（ジクロロメチルスルホニル）アミノ基、ビス（ジフルオロメチルスルホニル）アミノ基、ビス（トリフルオロメチルスルホニル）アミノ基、ビス（トリフルオロエチルスルホニル）アミノ基、ビス（ペンタフルオロエチルスルホニル）アミノ基等のビス（ハロアルキルスルホニル）アミノ基（ビス（Ｃ１−６ハロアルキルスルホニル）アミノ基が好ましい）；ヒドラジノ基、Ｎ'-フェニルヒドラジノ基、Ｎ'-メトキシカルボニヒドラジノ基等の無置換もしくは置換ヒドラジノメトキシカルボニル基；エトキシカルボニル基、プロポキシカルボニル基、イソプロポキシカルボニル基、ブトキシカルボニル基、ｔ−ブトキシカルボニル基等のアルコキシカルボニル基（Ｃ１−６アルコキシカルボニル基が好ましい）；フェニル基、１−ナフチル基、２−ナフチル基、ベンジル基、フェネチル基等のアリール基（Ｃ６−１２アリール基が好ましい）；フラン−２−イル基、フラン−３−イル基、チオフェン−２−イル基、チオフェン−３−イル基、ピロール−２−イル基、ピロール−３−イル基、オキサゾール−２−イル基、オキサゾール−４−イル基、オキサゾール−５−イル基、チアゾール−２−イル基、チアゾール−４−イル基、チアゾール−５−イル基、イソオキサゾール−３−イル基、イソオキサゾール−４−イル基、イソオキサゾール−５−イル基、イソチアゾール−３−イル基、イソチアゾール−４−イル基、イソチアゾール−５−イル基、イミダゾール−２−イル基、イミダゾール−４−イル基、イミダゾール−５−イル基、ピラゾール−３−イル基、ピラゾール−４−イル基、ピラゾール−５−イル基、１，３，４−オキサジアゾール−２−イル基、１，３，４−チアジアゾール−２−イル基、１，２，３−トリアゾール−４−イル基、１，２，４−トリアゾール−３−イル基、１，２，４−トリアゾール−５−イル基、５−フェニル−５−トリフルオロメチル−イソオキサゾリン−３−イル基、２−フルフリルメチル基、３−チエニルメチル基、１−メチル−３−ピラゾロメチル基等の不飽和複素５員環基；ピリジン−２−イル基、ピリジン−３−イル基、ピリジン−４−イル基、ピリダジン−３−イル基、ピリダジン−４−イル基、ピラジン−２−イル基、ピリミジン−２−イル基、ピリミジン−４−イル基、ピリミジン−５−イル基、１，３，５−トリアジン−２−イル基、１，２，４−トリアジン−３−イル基、２−ピリジルメチル基、３−ピリジルメチル基、６−クロル−３−ピリジルメチル基、２−ピリミジルメチル基等の不飽和複素６員環基；テトラヒドロフラン−２−イル基、テトラヒドラピラン−４−イル基、ピペリジン−３−イル基、ピロリジン−２−イル基、モルホリノ基、ピペリジノ基、Ｎ−メチルピペラジニル基、２−テトラヒドラフラニルメチル基、３−ピペラジルメチル基、Ｎ−メチル３−ピロリジルメチル基、モルホリノメチル基等の飽和複素環基；Ｎ−ジメチルアミノイミノメチル基、１−Ｎ−フェニルイミノエチル基、Ｎ−ヒドロキシイミノメチル基、Ｎ−メトキシイミノメチル基等のＮ無置換もしくはＮ置換イミノアルキル基；Ｎ’−メチルヒドラジノカルボニル基、Ｎ’−フェニルヒドラジノカルボニル基、ヒドラジノカルボニル基等のＮ無置換もしくはＮ置換ヒドラジノカルボニル基；アミノカルボニル基、ジメチルアミノカルボニル基、Ｎ−フェニル−Ｎ−メチルアミノカルボニル基等のＮ無置換もしくはＮ置換アミノカルボニル基；ヒドラジノ基、Ｎ’−アセチルヒドラジノ基、Ｎ’−メチルヒドラジノ基、Ｎ’−フェニルヒドラジノ基、Ｎ’−メトキシカルボニルヒドラジノ基、Ｎ’−２−プロピリデンヒドラジノ基等のＮ無置換もしくはＮ置換ヒドラジノ基；メチルチオ基、エチルチオ基、ｔ−ブチルチオ基等のアルキルチオ基；ビニルチオ基、アリルチオ基等のアルケニルチオ基；エチニルチオ基、プロパルギルチオ基等のアルキニルチオ基；フェニルチオ基、４−クロロフェニルチオ基、ベンジルチオ基、フェネチルチオ基、２−ピリジルチオ基等のアリールチオ基；メチルスルホニル基、エチルスルホニル基、ｔ−ブチルスルホニル基等のアルキルスルホニル基；アリルスルホニル基等のアルケニルスルホニル基；プロパルギルスルホニル基等のアルケニルスルホニル基；フェニルスルホニル基、ベンジルスルホニル基、２−ピリジルスルホニル基等のアリールスルホニル基等。Hydroxyl group; thiol group; halogen atom such as fluorine atom, chlorine atom, bromine atom, iodine atom; cyano group; nitro group; formyl group; amino group, methylamino group, benzylamino group, anilino group, dimethylamino group, diethylamino group An unsubstituted or substituted amino group such as phenylethylamino group; methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, t-butyl group, n-pentyl group Alkyl groups such as n-hexyl group (C 1-6 alkyl group is preferred); alkenyl groups such as vinyl group, allyl group, 2-methoxy-ethenyl group; ethynyl group, 1-propynyl group, 2-phenylethynyl group , Alkynyl groups such as propargyl group; methoxy group, ethoxy group, propoxy group, isopropoxy group, n-butoxy group, s alkoxy groups such as ec-butoxy group, isobutoxy group and t-butoxy group (C 1-6 alkoxy group is preferred); alkenyloxy groups such as vinyloxy group and allyloxy group; alkynyloxy groups such as ethynyloxy group and propargyloxy group ; Aryloxy groups such as phenoxy group, benzyloxy group, 2-pyridyloxy group; chloromethyl group, fluoromethyl group, bromomethyl group, dichloromethyl group, difluoromethyl group, dibromomethyl group, trichloromethyl group, trifluoromethyl group A haloalkyl group such as bromodifluoromethyl group, trifluoroethyl group, 1-chloroethyl group, 2-chloroethyl group, 1-bromoethyl group, 2-bromoethylpentafluoroethyl group (preferably a C 1-6 haloalkyl group); fluoro Methoxy group, black Halo such as methoxy group, bromomethoxy group, difluoromethoxy group, dichloromethoxy group, dibromomethoxy group, trifluoromethoxy group, trichloromethoxy group, tribromomethoxy group, trifluoroethoxy group, pentafluoroethoxy group, heptafluoropropoxy group Alkoxy group (C 1-6 haloalkoxy group is preferred); methylthiocarbonyl group, ethylthiocarbonyl group, propylthiocarbonyl group, isopropylthiocarbonyl group, butylthiocarbonyl group, isobutylthiocarbonyl group, sec-butylthicarbonyl group, alkyl thio group such as t- butyl thiocarbonyl (C 1-6 alkyl thio group is preferred); methylsulfonylamino group, ethylsulfonylamino group, propylsulfonyl group, Isopropyl sulfonylamino group, butyl sulfonylamino group, t- butyl alkylsulfonylamino group (C 1-6 alkylsulfonylamino group are preferred), such as sulfonylamino group; phenylsulfonylamino group, an aryl such as piperazinyl sulfonylamino group Sulfonylamino group (C 6-12 arylsulfonylamino group is preferred); alkylcarbonylamino groups such as methylcarbonylamino group, ethylcarbonylamino group, propylcarbonylamino group, isopropylcarbonylamino group (C 1-6 alkylcarbonylamino group) is preferred); methoxycarbonylamino group, ethoxycarbonylamino group, a propoxycarbonyl group, an alkoxycarbonylamino group (C 1-6 alkoxy such as isopropoxycarbonyl amino group Carbonylamino group is preferred); fluoromethylsulfonylamino group, chloromethylsulfonylamino group, bromomethylsulfonylamino group, difluoromethylsulfonylamino group, dichloromethylsulfonylamino group, difluoromethylsulfonylamino group, trifluoromethylsulfonylamino group, Haloalkylsulfonylamino groups such as trifluoroethylsulfonylamino group and pentafluoroethylsulfonylamino group (C 1-6 haloalkylsulfonylamino group is preferred); bis (methylsulfonyl) amino group, bis (ethylsulfonyl) amino group, (methyl Sulfonyl) (ethylsulfonyl) amino group, bis (propylsulfonyl) amino group, bis (isopropylsulfonyl) amino group, bis (butylsulfonyl) amino group Bis (t-butylsulfonyl) bis (alkylsulfonyl) amino group such as an amino group (bis (C 1-6 alkylsulfonyl) amino group are preferred); bis (fluoromethyl sulfonyl) amino group, bis (chloromethylsulfonyl) amino Group, bis (bromomethylsulfonyl) amino group, bis (difluoromethylsulfonyl) amino group, bis (dichloromethylsulfonyl) amino group, bis (difluoromethylsulfonyl) amino group, bis (trifluoromethylsulfonyl) amino group, bis ( Bis (haloalkylsulfonyl) amino group such as trifluoroethylsulfonyl) amino group and bis (pentafluoroethylsulfonyl) amino group (preferably bis (C 1-6 haloalkylsulfonyl) amino group); hydrazino group, N′-phenylhydra Zino group Unsubstituted or substituted hydrazinocarbonyl methoxycarbonyl group such as N'- methoxy carbonylation hydrazino group; an ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, an alkoxycarbonyl group such as a t- butoxycarbonyl group (C 1-6 alkoxycarbonyl group is preferred); aryl groups such as phenyl group, 1-naphthyl group, 2-naphthyl group, benzyl group, phenethyl group (C 6-12 aryl group is preferred); furan-2-yl group, Furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyrrol-2-yl group, pyrrol-3-yl group, oxazol-2-yl group, oxazol-4-yl group, oxazole -5-yl group, thiazol-2-yl group, thiazol-4-yl group, thiazole 5-yl group, isoxazol-3-yl group, isoxazol-4-yl group, isoxazol-5-yl group, isothiazol-3-yl group, isothiazol-4-yl group, isothiazol-5- Yl group, imidazol-2-yl group, imidazol-4-yl group, imidazol-5-yl group, pyrazol-3-yl group, pyrazol-4-yl group, pyrazol-5-yl group, 1,3,4 -Oxadiazol-2-yl group, 1,3,4-thiadiazol-2-yl group, 1,2,3-triazol-4-yl group, 1,2,4-triazol-3-yl group, 2,4-triazol-5-yl group, 5-phenyl-5-trifluoromethyl-isoxazolin-3-yl group, 2-furfurylmethyl group, 3-thienylmethyl group, 1-methyl-3-pi Unsaturated 5-membered ring groups such as zolomethyl group; pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group, pyridazin-3-yl group, pyridazin-4-yl group, pyrazine-2 -Yl group, pyrimidin-2-yl group, pyrimidin-4-yl group, pyrimidin-5-yl group, 1,3,5-triazin-2-yl group, 1,2,4-triazin-3-yl group Unsaturated 6-membered cyclic groups such as 2-pyridylmethyl group, 3-pyridylmethyl group, 6-chloro-3-pyridylmethyl group, 2-pyrimidylmethyl group; tetrahydrofuran-2-yl group, tetrahydrapyran-4- Yl group, piperidin-3-yl group, pyrrolidin-2-yl group, morpholino group, piperidino group, N-methylpiperazinyl group, 2-tetrahydrafuranylmethyl group, 3-piperazylmethyl group, N -Saturated heterocyclic group such as methyl 3-pyrrolidylmethyl group, morpholinomethyl group; N-dimethylaminoiminomethyl group, 1-N-phenyliminoethyl group, N-hydroxyiminomethyl group, N-methoxyiminomethyl group, etc. N-unsubstituted or N-substituted iminoalkyl group; N-unsubstituted or N-substituted hydrazinocarbonyl group such as N′-methylhydrazinocarbonyl group, N′-phenylhydrazinocarbonyl group, hydrazinocarbonyl group; N-unsubstituted or N-substituted aminocarbonyl groups such as dimethylaminocarbonyl group, N-phenyl-N-methylaminocarbonyl group; hydrazino group, N′-acetylhydrazino group, N′-methylhydrazino group, N′-phenyl Hydrazino group, N′-methoxycarbonylhydrazino group, N′-2-propylidene hydride N-unsubstituted or N-substituted hydrazino groups such as radino group; alkylthio groups such as methylthio group, ethylthio group and t-butylthio group; alkenylthio groups such as vinylthio group and allylthio group; alkynylthio groups such as ethynylthio group and propargylthio group Arylthio groups such as phenylthio group, 4-chlorophenylthio group, benzylthio group, phenethylthio group and 2-pyridylthio group; alkylsulfonyl groups such as methylsulfonyl group, ethylsulfonyl group and t-butylsulfonyl group; An alkenylsulfonyl group; an alkenylsulfonyl group such as a propargylsulfonyl group; an arylsulfonyl group such as a phenylsulfonyl group, a benzylsulfonyl group, and a 2-pyridylsulfonyl group;
これらの置換基は、１の置換基上に他の１の置換基を置換して２種以上を合体させて新たな置換基として同様に用いることができる。 These substituents can be similarly used as new substituents by substituting one other substituent on one substituent and combining two or more kinds.
本発明に使用される式（Ｉ）で表されるα−ヒドロキシ酸アンモニウム塩として具体的には、グリコール酸、乳酸、マンデル酸、α−ヒドロキシ酪酸、α−ヒドロキシイソ酪酸、α−ヒドロキシ−４−メチルチオ酪酸、α−ヒドロキシ−２−メチルプロピオン酸、α−ヒドロキシ−２−フェニルプロピオン酸、α，β−ジヒドロキシ−３，３−ジメチル酪酸、α−ヒドロキシ−３−ブテン酸、α−ヒドロキシ−３−メチル−３−ブテン酸、２−ピリジニル−α−ヒドロキシ酢酸等のアンモニウム塩を例示することができる。 Specific examples of the α-hydroxy acid ammonium salt represented by the formula (I) used in the present invention include glycolic acid, lactic acid, mandelic acid, α-hydroxybutyric acid, α-hydroxyisobutyric acid, and α-hydroxy-4. -Methylthiobutyric acid, α-hydroxy-2-methylpropionic acid, α-hydroxy-2-phenylpropionic acid, α, β-dihydroxy-3,3-dimethylbutyric acid, α-hydroxy-3-butenoic acid, α-hydroxy- Examples thereof include ammonium salts such as 3-methyl-3-butenoic acid and 2-pyridinyl-α-hydroxyacetic acid.
本発明で使用される式（Ｉ）で表されるα−ヒドロキシ酸アンモニウム塩の製造方法は、特に限定はされないが、具体的には、特公昭５８−１５１２０号公報、特開昭６３−２２２６９６号公報、特開昭６４−１０９９６号公報、特開平４−４０８９７号公報、特開平４−４０８９８号公報、特表平１０−５０７６３１号公報等に記載されているようにα−ヒドロキシニトリル類から微生物によって製造する方法を例示することができる。かかる微生物としては、アルスロバクター属に属する Arthrobacter sp. NSSC104 等を挙げることができる。 The production method of the α-hydroxy acid ammonium salt represented by the formula (I) used in the present invention is not particularly limited, and specifically, Japanese Examined Patent Publication No. 58-15120 and Japanese Unexamined Patent Publication No. 63-222696. As described in JP-A-64-10996, JP-A-4-40897, JP-A-4-40898, JP-A-10-507631, etc. A method for producing by microorganisms can be exemplified. Examples of such microorganisms include Arthrobacter sp. NSSC104 belonging to the genus Arthrobacter.
本発明の製造方法に用いられる薄膜蒸発装置は、熱効率を上げるために蒸発缶内部又は上部に水性溶媒溶液の液滴を供給して、薄膜を形成することができる装置であれば、特に限定されないが、攪拌式薄膜蒸発装置が好ましく、具体的には、環境ソリューション社製のワイプレン（登録商標）を例示することができ、また、竪型であるのが好ましい。 The thin film evaporation apparatus used in the production method of the present invention is not particularly limited as long as it can form a thin film by supplying droplets of an aqueous solvent solution inside or above the evaporator in order to increase thermal efficiency. However, a stirring-type thin film evaporator is preferable, and specifically, Wipelen (registered trademark) manufactured by Environmental Solutions Co., Ltd. can be exemplified, and a vertical type is preferable.
また、蒸発時に蒸発缶内部に、不活性ガス、又は空気を、投入する溶液と向流させるのが好ましい。不活性ガスとして具体的には、窒素ガス、アルゴンガスを例示することができる。 Further, it is preferable to counter-flow an inert gas or air into the evaporator during evaporation with the solution to be charged. Specific examples of the inert gas include nitrogen gas and argon gas.
流すガスの流量は、特に限定されないが、流量が少ない場合、アンモニアの分離が悪くなる傾向にあり、薄膜蒸発装置の伝熱部分の塔断面積に対するガス空塔速度を０．０１ｍ／ｓ以上とするのが好ましい。上限については、フラッディングを引き起こさない範囲であれば、分離効率、及び処理能力が落ちない限り、特に制限されない。 The flow rate of the flowing gas is not particularly limited, but when the flow rate is small, the ammonia separation tends to deteriorate, and the gas superficial velocity with respect to the cross-sectional area of the heat transfer portion of the thin film evaporator is 0.01 m / s or more. It is preferable to do this. About an upper limit, if it is a range which does not cause flooding, unless a separation efficiency and processing capacity fall, it will not restrict | limit in particular.
また、水性溶媒溶液に対するガスの量は、フラッディングを引き起こさない範囲であれば、特に限定されないが、蒸発装置に投入する水性溶媒溶液１ｇに対して１．６Ｌ以上が好ましく、これにより分離効率、及び処理能力が向上する。 Further, the amount of the gas with respect to the aqueous solvent solution is not particularly limited as long as it does not cause flooding, but is preferably 1.6 L or more with respect to 1 g of the aqueous solvent solution to be charged into the evaporation apparatus, and thereby separation efficiency, and Processing capacity is improved.
薄膜蒸発装置に投入される水性溶媒溶液の量は、加熱温度、撹拌速度、ガスの流量等の装置の設定値によって適宜選択することが可能であるが、少なくともＬ／分を単位とするガスの流量の数値とｇ／分を単位とする水性溶媒溶液の投入量の数値を比較した場合に、ガス流量の数値が大きくなるように設定するのが好ましい。また、投入される水性溶媒溶液は、熱効率を上げるために予め蒸発缶の加熱温度付近まで加熱しておくのが好ましい。 The amount of the aqueous solvent solution charged into the thin film evaporation apparatus can be appropriately selected depending on the set values of the apparatus such as the heating temperature, the stirring speed, and the gas flow rate. When the numerical value of the flow rate is compared with the numerical value of the input amount of the aqueous solvent solution in units of g / min, it is preferable to set the numerical value of the gas flow rate to be large. Moreover, it is preferable that the aqueous solvent solution to be added is heated in advance to around the heating temperature of the evaporator in order to increase the thermal efficiency.
薄膜蒸発装置の加熱温度は、化合物によって適宜設定することができるが、水性溶媒溶液であることから、１００℃以上が好ましく、さらに、１５０℃以上が好ましい。上限は化合物の熱安定性によって適宜設定することができるが、１７５℃以下が好ましい。 The heating temperature of the thin film evaporator can be appropriately set depending on the compound, but is preferably 100 ° C. or higher, and more preferably 150 ° C. or higher because it is an aqueous solvent solution. Although an upper limit can be suitably set with the thermal stability of a compound, 175 degrees C or less is preferable.
以下、実施例を用いて本発明をさらに詳細に説明するが、本発明の範囲は、実施例に限定されるものではない。
(実施例１〜７及び比較例１)EXAMPLES Hereinafter, although this invention is demonstrated further in detail using an Example, the scope of the present invention is not limited to an Example.
(Examples 1-7 and Comparative Example 1)
薄膜蒸発機として環境ソリューション社製ワイプレンテスト機を使用した。そのテスト機の仕様は以下の通りである。
・型式：撹拌式竪型接触式薄膜蒸発機
・シェルの内径：１５６ｍｍ
・直胴部の長さ：６０５ｍｍ
・伝熱面積：０．２ｍ２
・ワイパー回転数：９３〜３６７ｒｐｍ
３２．４重量％の２−ヒドロキシ−４−メチルチオブタン酸アンモニウム塩水溶液を原料として用いた。原料を原料槽に仕込み、表に示す所定温度に加温した。原料が所定温度に到達したら、ワイプレン本体を加熱し、表に示す所定の温度に達したところで、原料ポンプを運転させ、本体に原料を供給開始した。原料供給開始とともに、ワイパーの回転を開始した。処理された液は、残留液受器に貯められた。空気は、ワイプレン本体の下部から供給し、発生ガス（アンモニア、水蒸気）とともに上部から排出され、硫酸トラップ、次亜塩素酸ソーダトラップ、洗浄塔を経由して大気に放出した。なお、アンモニアの遊離蒸発後のα−ヒドロキシ酸とα−ヒドロキシ酸アンモニウム塩の定量は、両方の合計量を高速液体クロマトグラフィーにより定量し、アンモニア分をＮＡＤＨ〜グルタミン酸脱水素酵素を用いる紫外部吸光度測定法（Methods of Enzymatic Analysis, BergmeyerH.
U.ed., 3rd ed., vol.8, pp.454-461）により定量し、その当量分をα−ヒドロキシ酸アンモニウム塩とした。A wiper test machine manufactured by Environmental Solutions was used as the thin film evaporator. The specifications of the test machine are as follows.
・ Model: Stirring type vertical contact type thin film evaporator ・ Inner diameter of shell: 156 mm
・ Length of straight body: 605mm
-Heat transfer area: 0.2m 2
-Wiper rotation speed: 93-367rpm
An aqueous solution of 32.4% by weight ammonium 2-hydroxy-4-methylthiobutanoate was used as a raw material. The raw material was charged into a raw material tank and heated to a predetermined temperature shown in the table. When the raw material reached a predetermined temperature, the wiper main body was heated, and when the predetermined temperature shown in the table was reached, the raw material pump was operated to start supplying the raw material to the main body. With the start of raw material supply, the wiper started rotating. The treated liquid was stored in a residual liquid receiver. Air was supplied from the lower part of the main body of the wiper, discharged from the upper part together with the generated gas (ammonia, water vapor), and discharged to the atmosphere via a sulfuric acid trap, a sodium hypochlorite trap and a washing tower. In addition, quantification of α-hydroxy acid and α-hydroxy acid ammonium salt after free evaporation of ammonia was performed by quantifying the total amount of both by high performance liquid chromatography, and measuring the ultraviolet content using NADH to glutamate dehydrogenase. Methods of Enzymatic Analysis, BergmeyerH.
U.ed., 3rd ed., Vol.8, pp.454-461), and the equivalent was defined as α-hydroxy acid ammonium salt.
空気流量(ｍ／秒)：攪拌式薄膜蒸発装置の伝熱部分の塔断面積に対するガス空塔速度
Air flow rate (m / sec): Gas superficial velocity with respect to the cross-sectional area of the heat transfer section of the stirred thin film evaporator
本発明によると、α−ヒドロキシ酸のアンモニウム塩からその遊離酸であるα−ヒドロキシ酸をエネルギーコストを低く抑えて、工業的に有利に効率よく製造することができる。 According to the present invention, an α-hydroxy acid, which is a free acid, can be produced from an ammonium salt of an α-hydroxy acid at an industrially advantageous and efficient production while keeping the energy cost low.
Claims (7)
ＲＣＨ（ＯＨ）ＣＯＯ−ＮＨ４ ＋ （Ｉ）
(式中、Ｒは水素原子、Ｃ１〜Ｃ６アルキル基、Ｃ２〜Ｃ６アルケニル基、Ｃ１〜Ｃ６アルコキシ基、アリール基、アリールオキシ基又は複素環基を表す。）で表されるα−ヒドロキシ酸アンモニウム塩の水性溶媒溶液を、薄膜蒸発装置を用いて、加熱を行いながら不活性ガス又は空気を、攪拌式薄膜蒸発装置の伝熱部分の塔断面積に対するガス空塔速度が０．０２ｍ／ｓ以上で、前記水性溶媒溶液と向流させることで、アンモニアを遊離させ、水性溶媒とともに蒸発させることを特徴とする、式（ＩＩ）
ＲＣＨ（ＯＨ）ＣＯＯＨ （ＩＩ）
(式中、Ｒは前記と同じ意味を表す。)で表されるα−ヒドロキシ酸の製造方法。Formula (I)
RCH (OH) COO - NH 4 + (I)
(In the formula, R represents a hydrogen atom, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, an aryl group, an aryloxy group, or a heterocyclic group). An inert gas or air is heated while heating an aqueous solvent solution of a salt using a thin film evaporator, and a gas superficial velocity with respect to the cross-sectional area of the heat transfer portion of the stirred thin film evaporator is 0.02 m / s. Thus, the ammonia is liberated by countercurrent with the aqueous solvent solution and evaporated together with the aqueous solvent. Formula (II)
RCH (OH) COOH (II)
(Wherein, R represents the same meaning as described above).
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| PCT/JP2008/002001 WO2009013909A1 (en) | 2007-07-25 | 2008-07-25 | Method for production of α-hydroxy acid from ammonium salt of the α-hydroxy acid |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6150937A (en) * | 1984-08-20 | 1986-03-13 | Asahi Chem Ind Co Ltd | Production of carboxylic acid from aqueous solution of ammonium carboxylate |
| WO1997030962A1 (en) * | 1996-02-26 | 1997-08-28 | Nippon Soda Co., Ltd. | PROCESS FOR PREPARING FREE α-HYDROXY ACIDS FROM AMMONIUM SALTS THEREOF |
| WO1998018941A1 (en) * | 1996-10-25 | 1998-05-07 | Rhone-Poulenc Nutrition Animale | Method for preparing 2-hydroxy 4-methylthio butyric acid using a nitrilase |
| JPH10179183A (en) * | 1996-12-20 | 1998-07-07 | Daicel Chem Ind Ltd | Production of carboxylic acid |
| JP2000119214A (en) * | 1998-10-16 | 2000-04-25 | Nippon Soda Co Ltd | Production of alpha-hydroxy acid from ammonium salt of alpha-hydroxy acid |
-
2008
- 2008-07-25 JP JP2009524401A patent/JP5143838B2/en active Active
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6150937A (en) * | 1984-08-20 | 1986-03-13 | Asahi Chem Ind Co Ltd | Production of carboxylic acid from aqueous solution of ammonium carboxylate |
| WO1997030962A1 (en) * | 1996-02-26 | 1997-08-28 | Nippon Soda Co., Ltd. | PROCESS FOR PREPARING FREE α-HYDROXY ACIDS FROM AMMONIUM SALTS THEREOF |
| WO1998018941A1 (en) * | 1996-10-25 | 1998-05-07 | Rhone-Poulenc Nutrition Animale | Method for preparing 2-hydroxy 4-methylthio butyric acid using a nitrilase |
| JPH10179183A (en) * | 1996-12-20 | 1998-07-07 | Daicel Chem Ind Ltd | Production of carboxylic acid |
| JP2000119214A (en) * | 1998-10-16 | 2000-04-25 | Nippon Soda Co Ltd | Production of alpha-hydroxy acid from ammonium salt of alpha-hydroxy acid |
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