JP2011074016A - Method of manufacturing 3-mercapto-1-propanol - Google Patents
Method of manufacturing 3-mercapto-1-propanol Download PDFInfo
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- JP2011074016A JP2011074016A JP2009227316A JP2009227316A JP2011074016A JP 2011074016 A JP2011074016 A JP 2011074016A JP 2009227316 A JP2009227316 A JP 2009227316A JP 2009227316 A JP2009227316 A JP 2009227316A JP 2011074016 A JP2011074016 A JP 2011074016A
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- 3mpo
- allyl alcohol
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- SHLSSLVZXJBVHE-UHFFFAOYSA-N 3-sulfanylpropan-1-ol Chemical compound OCCCS SHLSSLVZXJBVHE-UHFFFAOYSA-N 0.000 title claims abstract description 83
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 claims abstract description 60
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 1
- -1 aluminum lithium hydride Chemical compound 0.000 abstract description 8
- 238000006243 chemical reaction Methods 0.000 description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 16
- 239000001301 oxygen Substances 0.000 description 16
- 229910052760 oxygen Inorganic materials 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 239000007789 gas Substances 0.000 description 11
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 239000013067 intermediate product Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- ADIJNQVLNHDJIF-UHFFFAOYSA-N S-(3-hydroxypropyl)-thioacetate Chemical compound CC(=O)SCCCO ADIJNQVLNHDJIF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000007789 sealing Methods 0.000 description 6
- 238000001577 simple distillation Methods 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000012776 electronic material Substances 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000007259 addition reaction Methods 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical compound CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- YTMKRLBDTWYHLW-UHFFFAOYSA-N S-(3-hydroxypropyl) propanethioate Chemical compound CCC(=O)SCCCO YTMKRLBDTWYHLW-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000007791 dehumidification Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 229960005335 propanol Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 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
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/28—Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
本発明は、医薬品、農薬、電子材料などの製造用中間体として有用な3−メルカプト−1−プロパノール(「3−スルファニル−1−プロパノール」ともいう)の新規製造方法に関する。 The present invention relates to a novel method for producing 3-mercapto-1-propanol (also referred to as “3-sulfanyl-1-propanol”) useful as an intermediate for production of pharmaceuticals, agricultural chemicals, electronic materials and the like.
3−メルカプト−1−プロパノール(以下「3MPO」と略称することがある)は、電子材料の製造用中間体(特許文献1)、除草剤成分の製造用中間体(特許文献2)及び医薬品の製造用中間体(非特許文献1)として有用である。3MPOの製造方法としては、これまで、下記(a)及び(b)の方法が知られている。 3-mercapto-1-propanol (hereinafter sometimes abbreviated as “3MPO”) is an intermediate for producing electronic materials (Patent Document 1), an intermediate for producing herbicide components (Patent Document 2), and pharmaceutical products. It is useful as an intermediate for production (Non-Patent Document 1). As a method for producing 3MPO, the following methods (a) and (b) have been known so far.
(a)下記式で表されるように、3−メルカプトプロピオン酸を水素化アルミニウムリチウム(LiAlH4)で還元する方法(非特許文献2)。 (A) A method of reducing 3-mercaptopropionic acid with lithium aluminum hydride (LiAlH 4 ) as represented by the following formula (Non-patent Document 2).
(b)下記式で表されるように、3−クロロ−1−プロパノールとチオ尿素とを反応させた後、中間生成物を水酸化ナトリウムで加水分解する方法(非特許文献3)。 (B) A method of reacting 3-chloro-1-propanol with thiourea and then hydrolyzing the intermediate product with sodium hydroxide as represented by the following formula (Non-patent Document 3).
上記製法(a)は、自然発火性の水素化アルミニウムリチウムを使用しているため、工業生産に適さない。また上記製法(b)は、3MPOの収率が40%程度と低い。そこで本発明の目的は、発火性の水素化アルミニウムリチウムを使用せず、且つ高収率で3MPOを製造する方法を提供しようとするものである。 Since the said manufacturing method (a) uses pyrophoric lithium aluminum hydride, it is not suitable for industrial production. In addition, the production method (b) has a low yield of 3MPO of about 40%. Therefore, an object of the present invention is to provide a method for producing 3MPO in a high yield without using ignitable lithium aluminum hydride.
上記目的を達成し得た本発明の3−メルカプト−1−プロパノールの製造方法は、
アリルアルコールに式(1)で表される化合物を付加させて式(2)で表される化合物を合成し、次いで式(2)で表される化合物を加水分解して3−メルカプト−1−プロパノールを合成することを特徴とする(下記式中、R1はアルキル基を表す。)。
The method for producing 3-mercapto-1-propanol according to the present invention, which has achieved the above object,
A compound represented by formula (1) is added to allyl alcohol to synthesize a compound represented by formula (2), and then the compound represented by formula (2) is hydrolyzed to give 3-mercapto-1- Propanol is synthesized (in the following formula, R 1 represents an alkyl group).
以下では、「式(1)で表される化合物」及び「式(2)で表される化合物」を、それぞれ「化合物(1)」及び「化合物(2)」と略称する。 Hereinafter, the “compound represented by the formula (1)” and the “compound represented by the formula (2)” are abbreviated as “compound (1)” and “compound (2)”, respectively.
化合物(1)は、チオ−S−酢酸であることが好ましい。また化合物(2)の加水分解は、塩酸及び硫酸よりなる群から選ばれる少なくとも1種、又はアンモニア及びヒドラジンよりなる群から選ばれる少なくとも1種の存在下で行うことが好ましい。 Compound (1) is preferably thio-S-acetic acid. The hydrolysis of the compound (2) is preferably performed in the presence of at least one selected from the group consisting of hydrochloric acid and sulfuric acid, or at least one selected from the group consisting of ammonia and hydrazine.
本発明の製造方法によれば、発火性の水素化アルミニウムリチウムを使用せず、且つ高収率で3−メルカプト−1−プロパノール(3MPO)を得ることができる。 According to the production method of the present invention, 3-mercapto-1-propanol (3MPO) can be obtained in high yield without using ignitable lithium aluminum hydride.
本発明の製造方法は、アリルアルコールへの化合物(1)の付加反応(第1反応)、及び第1反応で得られた化合物(2)の加水分解反応(第2反応)によって、安価で入手しやすいアリルアルコールから3MPOを高収率で製造できることを特徴とする。以下、第1反応及び第2反応を順に説明する。 The production method of the present invention is obtained at low cost by the addition reaction (first reaction) of compound (1) to allyl alcohol and the hydrolysis reaction (second reaction) of compound (2) obtained in the first reaction. It is characterized in that 3MPO can be produced in high yield from allyl alcohol which is easy to do. Hereinafter, the first reaction and the second reaction will be described in order.
〈第1反応〉
第1反応で使用する化合物(1)はチオ−S−カルボン酸であり、アリルアルコールと同様、容易に入手できる。化合物(1)は、1種を単独で使用してもよく、2種以上を併用してもよい。化合物(1)中のアルキル基R1の炭素数は、好ましくは1〜10、より好ましくは1〜4である。R1としては、例えばメチル基、エチル基、プロピル基、イソプロピル基、ブチル基、ブタン−2−イル基、2−メチルプロピル基、2−メチルプロパン−2−イル基などが挙げられ、これらの中でもメチル基{即ち化合物(1)がチオ−S−酢酸である場合}、エチル基{即ち化合物(1)がチオ−S−プロピオン酸である場合}が好ましく、メチル基がより好ましい。化合物(1)の使用量は、アリルアルコール1モルに対して、好ましくは1.0〜2.0モル、より好ましくは1.0〜1.5モルである。
<First reaction>
The compound (1) used in the first reaction is a thio-S-carboxylic acid and can be easily obtained in the same manner as allyl alcohol. A compound (1) may be used individually by 1 type, and may use 2 or more types together. Compound (1) the number of carbon atoms in the alkyl group R 1 in is preferably 1 to 10, more preferably 1-4. Examples of R 1 include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a butan-2-yl group, a 2-methylpropyl group, and a 2-methylpropan-2-yl group. Among them, a methyl group {that is, when the compound (1) is thio-S-acetic acid}, an ethyl group {that is, when the compound (1) is thio-S-propionic acid} is preferable, and a methyl group is more preferable. The amount of compound (1) to be used is preferably 1.0 to 2.0 mol, more preferably 1.0 to 1.5 mol, per 1 mol of allyl alcohol.
アリルアルコールへの化合物(1)の付加反応(第1反応)は、好ましくはラジカル発生剤の存在下で行われる。ラジカル発生剤としては、ラジカル重合に使用される公知の重合開始剤(例えば2,2'−アゾビスイソブチロニトリル)や酸素などが使用でき、これらの中でも酸素が好ましい。ラジカル発生剤として酸素を使用する場合、酸素含有ガス雰囲気下で第1反応を行えばよい。ガス雰囲気の酸素濃度は、好ましくは1〜20体積%程度である。酸素以外のガス雰囲気は、不活性ガス(例えば窒素)であることが好ましい。ラジカル開始剤である酸素の供給法としては、例えば、(i)反応開始前に所定濃度の酸素を含有するガス雰囲気にし、系を密閉にしてから第1反応を行う方法や、(ii)第1反応を行っている間に所定濃度の酸素を含有するガスを供給し続ける方法など、様々な方法を採用できる。 The addition reaction (first reaction) of compound (1) to allyl alcohol is preferably carried out in the presence of a radical generator. As the radical generator, a known polymerization initiator (for example, 2,2′-azobisisobutyronitrile) used for radical polymerization or oxygen can be used, and among these, oxygen is preferable. When oxygen is used as the radical generator, the first reaction may be performed in an oxygen-containing gas atmosphere. The oxygen concentration in the gas atmosphere is preferably about 1 to 20% by volume. The gas atmosphere other than oxygen is preferably an inert gas (for example, nitrogen). As a method for supplying oxygen as a radical initiator, for example, (i) a method in which a gas atmosphere containing a predetermined concentration of oxygen is set before starting the reaction, the system is sealed, and the first reaction is performed; Various methods such as a method of continuously supplying a gas containing oxygen at a predetermined concentration during one reaction can be employed.
第1反応は、無溶媒で行ってもよく、反応を阻害しない溶媒中で行ってもよい。溶媒は、1種を単独で使用してもよく、2種以上を併用してもよい。第1反応の溶媒としては、例えばペンタン、ヘキサン、シクロヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類;ジクロロメタン、クロロホルム、四塩化炭素、ジクロロエタン、ジクロロプロパン等のハロゲン化炭化水素類;酢酸、プロピオン酸等のカルボン酸類;などが挙げられる。溶媒を使用する場合、その量は、アリルアルコール1gに対して、好ましくは50mL以下、より好ましくは15mL以下である。ラジカル開始剤として酸素を使用する場合、第1反応は、無溶媒又はハロゲン化炭化水素類中で行うことが好ましく;無溶媒或いはジクロロメタン、クロロホルム又はこれらの混合溶媒中で行うことがより好ましい。 The first reaction may be performed without a solvent or in a solvent that does not inhibit the reaction. A solvent may be used individually by 1 type and may use 2 or more types together. Examples of the solvent for the first reaction include aliphatic hydrocarbons such as pentane, hexane, cyclohexane, heptane and octane; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane and dichloropropane; acetic acid and propionic acid Carboxylic acids such as; and the like. When using a solvent, the amount thereof is preferably 50 mL or less, more preferably 15 mL or less, with respect to 1 g of allyl alcohol. When oxygen is used as the radical initiator, the first reaction is preferably carried out without solvent or in halogenated hydrocarbons; more preferably without solvent or in dichloromethane, chloroform or a mixed solvent thereof.
第1反応の反応温度は、好ましくは10〜100℃程度、より好ましくは20〜80℃程度であり、その反応時間は、好ましくは0.1〜24時間程度、より好ましくは0.5〜10時間程度である。 The reaction temperature of the first reaction is preferably about 10 to 100 ° C., more preferably about 20 to 80 ° C., and the reaction time is preferably about 0.1 to 24 hours, more preferably 0.5 to 10 ° C. It is about time.
第1反応終了後に得られた反応混合物を、そのまま第2反応に使用してもよく、また未反応のアリルアルコール及び化合物(1)、並びに場合により使用した溶媒を留去して化合物(2)を単離し、これを第2反応に使用してもよい。 The reaction mixture obtained after completion of the first reaction may be used for the second reaction as it is, or unreacted allyl alcohol and compound (1) and optionally used solvent are distilled off to remove compound (2). May be isolated and used in the second reaction.
〈第2反応〉
チオカルボン酸S−(3−ヒドロキシプロピル)である化合物(2)の加水分解反応(第2反応)は、好ましくは酸又は塩基の存在下で行われる。酸は、1種を単独で使用してもよく、2種以上を併用してもよい。同様に塩基も、1種を単独で使用してもよく、2種以上を併用してもよい。
<Second reaction>
The hydrolysis reaction (second reaction) of compound (2) which is thiocarboxylic acid S- (3-hydroxypropyl) is preferably performed in the presence of an acid or a base. An acid may be used individually by 1 type and may use 2 or more types together. Similarly, the base may be used alone or in combination of two or more.
酸は、無機酸及び有機酸のいずれも使用できる。無機酸としては、例えば、塩酸、臭化水素、硫酸、硝酸、リン酸、ホウ酸、アジ化水素、塩素酸、臭素酸、炭酸、硫化水素などが挙げられる。有機酸としては、例えば、トリフルオロ酢酸、メタンスルホン酸、トリフルオロメタンスルホン酸、ベンゼンスルホン酸、トルエンスルホン酸などが挙げられる。好ましい酸は、塩酸、硫酸、トリフルオロ酢酸、及びメタンスルホン酸であり、より好ましい酸は、塩酸及び硫酸である。酸を使用する場合、その量は、化合物(2)1モルに対して、好ましくは0.001〜1.0モル、より好ましくは0.05〜0.5モルである。 As the acid, either an inorganic acid or an organic acid can be used. Examples of the inorganic acid include hydrochloric acid, hydrogen bromide, sulfuric acid, nitric acid, phosphoric acid, boric acid, hydrogen azide, chloric acid, bromic acid, carbonic acid, hydrogen sulfide and the like. Examples of the organic acid include trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, and the like. Preferred acids are hydrochloric acid, sulfuric acid, trifluoroacetic acid, and methanesulfonic acid, and more preferred acids are hydrochloric acid and sulfuric acid. When an acid is used, the amount thereof is preferably 0.001 to 1.0 mol, more preferably 0.05 to 0.5 mol, per 1 mol of compound (2).
塩基としては、例えば、水酸化ナトリウム、水酸化カリウム、ヒドラジン、及びアンモニアなどが挙げられ、これらの中でもヒドラジン及びアンモニアが好ましい。塩基を使用する場合、その量は、化合物(2)1モルに対して、好ましくは1.0〜5.0モル、より好ましくは1.0〜3.0モルである。 Examples of the base include sodium hydroxide, potassium hydroxide, hydrazine, and ammonia. Among these, hydrazine and ammonia are preferable. When a base is used, the amount thereof is preferably 1.0 to 5.0 mol, more preferably 1.0 to 3.0 mol, per 1 mol of compound (2).
加水分解反応(第2反応)は、好ましくは、溶媒中で行われる。溶媒は、1種を単独で使用してもよく、2種以上を併用してもよい。第2反応の溶媒としては、例えばペンタン、ヘキサン、シクロヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類;ジエチルエーテル、ジイソプロピルエーテル、テトラヒドロフラン、ジメトキシエタン、シクロペンチルメチルエーテル、tert−ブチルメチルエーテル、アニソール等のエーテル類;ベンゼン、トルエン、キシレン等の芳香族炭化水素類;ジクロロメタン、クロロホルム、四塩化炭素、ジクロロエタン、ジクロロプロパン等のハロゲン化炭化水素類;メタノール、エタノール、プロパノール、イソプロパノール、ブタノール、イソブタノール、tert−ブタノールなどのアルコール類;アセトニトリル、N,N−ジメチルホルムアミド、N,N−ジメチルアセトアミド、N−メチル−2−ピロリドン、1,3−ジメチル−2−イミダゾリジノンなどの非プロトン性極性溶媒;水などが挙げられ、これらの中でも、メタノール、水、及びメタノールと水との混合溶媒が好ましい。第2反応の溶媒量は、化合物(2)1gに対して、好ましくは0.5〜50mL、より好ましくは1〜15mLである。 The hydrolysis reaction (second reaction) is preferably performed in a solvent. A solvent may be used individually by 1 type and may use 2 or more types together. Examples of the solvent for the second reaction include aliphatic hydrocarbons such as pentane, hexane, cyclohexane, heptane, and octane; diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, cyclopentyl methyl ether, tert-butyl methyl ether, anisole, and the like. Ethers; aromatic hydrocarbons such as benzene, toluene, xylene; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, dichloropropane; methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tert Alcohols such as butanol; acetonitrile, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, 1,3-dimethyl -2 aprotic polar solvents such as imidazolidinone; and water. Among these, methanol, water, and a mixed solvent of methanol and water preferred. The amount of the solvent in the second reaction is preferably 0.5 to 50 mL, more preferably 1 to 15 mL with respect to 1 g of compound (2).
第2反応の反応温度は、使用する溶媒に応じて、好ましくは10〜120℃程度、より好ましくは20〜100℃程度であり、その反応時間は、好ましくは0.1〜24時間程度、より好ましくは0.5〜10時間程度である。 The reaction temperature of the second reaction is preferably about 10 to 120 ° C., more preferably about 20 to 100 ° C., depending on the solvent used, and the reaction time is preferably about 0.1 to 24 hours. Preferably it is about 0.5 to 10 hours.
第2反応の終了後、クエンチ、抽出、洗浄、脱湿、溶媒留去などの常法によって3MPOの粗生成物を得た後、粗生成物を精製することが好ましい。精製手段としては、例えば蒸留、カラムクロマトグラフィー、結晶化などが挙げられる。 After completion of the second reaction, it is preferable to purify the crude product after obtaining a crude product of 3MPO by a conventional method such as quenching, extraction, washing, dehumidification, and solvent evaporation. Examples of the purification means include distillation, column chromatography, crystallization and the like.
以下、実施例を挙げて本発明をより具体的に説明するが、本発明は以下の実施例によって制限を受けるものではなく、上記・下記の趣旨に適合し得る範囲で適当に変更を加えて実施することも勿論可能であり、それらはいずれも本発明の技術的範囲に包含される。 EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited by the following examples, and appropriate modifications are made within a range that can meet the above and the following purposes. Of course, it is possible to implement them, and they are all included in the technical scope of the present invention.
実施例1
100mLフラスコに、アリルアルコール(5.8g、100mmol)及びクロロホルム(60mL)を加え、フラスコ内のガス雰囲気を窒素濃度約85体積%及び酸素濃度約15体積%にして密閉した後、フラスコ内容物を50〜60℃に昇温し、チオ−S−酢酸(8.0g、105mmol)を滴下した。滴下終了後、50〜60℃で2時間反応させた。反応終了後、50℃でクロロホルムを減圧留去することによって、微黄色液体のチオ酢酸S−(3−ヒドロキシプロピル)を12.5g(93mmol、アリルアルコールに対して収率93%)で得た。
Example 1
After adding allyl alcohol (5.8 g, 100 mmol) and chloroform (60 mL) to a 100 mL flask and sealing the gas atmosphere in the flask with a nitrogen concentration of about 85 vol% and an oxygen concentration of about 15 vol%, the flask contents were The temperature was raised to 50-60 ° C., and thio-S-acetic acid (8.0 g, 105 mmol) was added dropwise. After completion of dropping, the reaction was carried out at 50 to 60 ° C. for 2 hours. After completion of the reaction, chloroform was distilled off under reduced pressure at 50 ° C. to obtain 12.5 g (93 mmol, 93% yield with respect to allyl alcohol) of thioacetic acid S- (3-hydroxypropyl) as a slightly yellow liquid. .
200mLフラスコに、上記のようにして得た全量のチオ酢酸S−(3−ヒドロキシプロピル)(12.5g、93mmol)、ヒドラジン一水和物(5.1g、102mmol)及びメタノール(100mL)を加え、20〜30℃で1時間反応させた。反応終了後にメタノールを留去し、水(30mL)を加え、クロロホルム(50mL×3回)で抽出した。抽出したクロロホルム層を無水硫酸マグネシウム(10g)で脱湿し、無水硫酸マグネシウムをろ過し、クロロホルムを留去することによって得られた粗生成物を単蒸留(15Torr、90℃)することによって、微黄色液体の3MPOを7.2g(78mmol)で得た。3MPOの収率は、中間生成物であるチオ酢酸S−(3−ヒドロキシプロピル)に対して84%であり、出発原料であるアリルアルコールに対して78%であった。 To the 200 mL flask, add the total amount of thioacetic acid S- (3-hydroxypropyl) (12.5 g, 93 mmol), hydrazine monohydrate (5.1 g, 102 mmol) and methanol (100 mL) obtained as described above. It was made to react at 20-30 degreeC for 1 hour. After completion of the reaction, methanol was distilled off, water (30 mL) was added, and the mixture was extracted with chloroform (50 mL × 3 times). The extracted chloroform layer was dehumidified with anhydrous magnesium sulfate (10 g), the anhydrous magnesium sulfate was filtered, and the crude product obtained by distilling off the chloroform was subjected to simple distillation (15 Torr, 90 ° C.). The yellow liquid 3MPO was obtained in 7.2 g (78 mmol). The yield of 3MPO was 84% based on the intermediate product S- (3-hydroxypropyl) thioacetate and 78% based on the starting material, allyl alcohol.
実施例1で得られた3MPOの1H−NMR(CDCl3)
δ=3.75(t、2H)、2.63(m、2H)、1.87(m、2H)、1.48(m、1H)、1.38(t、1H)
1 H-NMR (CDCl 3 ) of 3MPO obtained in Example 1
δ = 3.75 (t, 2H), 2.63 (m, 2H), 1.87 (m, 2H), 1.48 (m, 1H), 1.38 (t, 1H)
実施例2
100mLフラスコに、アリルアルコール(5.8g、100mmol)及びクロロホルム(30mL)を加え、フラスコ内のガス雰囲気を窒素濃度約85体積%及び酸素濃度約15体積%にして密閉した後、フラスコ内容物を50〜60℃に昇温し、チオ−S−酢酸(8.0g、105mmol)を滴下した。滴下終了後、50〜60℃で2時間反応させた。反応終了後、50℃でクロロホルムを減圧留去することによって、微黄色液体のチオ酢酸S−(3−ヒドロキシプロピル)を12.1g(90mmol、アリルアルコールに対して収率90%)で得た。
Example 2
After adding allyl alcohol (5.8 g, 100 mmol) and chloroform (30 mL) to a 100 mL flask and sealing the gas atmosphere in the flask with a nitrogen concentration of about 85 vol% and an oxygen concentration of about 15 vol%, the flask contents were The temperature was raised to 50-60 ° C., and thio-S-acetic acid (8.0 g, 105 mmol) was added dropwise. After completion of dropping, the reaction was carried out at 50 to 60 ° C. for 2 hours. After completion of the reaction, chloroform was distilled off under reduced pressure at 50 ° C. to obtain 12.1 g (90 mmol, yield 90% with respect to allyl alcohol) of thioacetic acid S- (3-hydroxypropyl) as a slightly yellow liquid. .
100mLフラスコに、上記のようにして得た全量のチオ酢酸S−(3−ヒドロキシプロピル)(12.1g、90mmol)、28%アンモニア水溶液(13.7g、225mmol)及び水(30mL)を加え、20〜30℃で5時間反応させた。反応終了後にクロロホルム(50mL×3回)で抽出した。抽出したクロロホルム層を無水硫酸マグネシウム(10g)で脱湿し、無水硫酸マグネシウムをろ過し、クロロホルムを留去することによって得られた粗生成物を単蒸留(15Torr、90℃)することによって、微黄色液体の3MPOを6.5g(70mmol)で得た。3MPOの収率は、中間生成物であるチオ酢酸S−(3−ヒドロキシプロピル)に対して78%であり、出発原料であるアリルアルコールに対して70%であった。 To a 100 mL flask was added the total amount of thioacetic acid S- (3-hydroxypropyl) (12.1 g, 90 mmol) obtained above, 28% aqueous ammonia (13.7 g, 225 mmol) and water (30 mL), It was made to react at 20-30 degreeC for 5 hours. After completion of the reaction, the mixture was extracted with chloroform (50 mL × 3 times). The extracted chloroform layer was dehumidified with anhydrous magnesium sulfate (10 g), the anhydrous magnesium sulfate was filtered, and the crude product obtained by distilling off the chloroform was subjected to simple distillation (15 Torr, 90 ° C.). The yellow liquid 3MPO was obtained in 6.5 g (70 mmol). The yield of 3MPO was 78% with respect to the intermediate product S- (3-hydroxypropyl) thioacetate and 70% with respect to the starting material allyl alcohol.
実施例2で得られた3MPOの1H−NMR(CDCl3)
δ=3.75(t、2H)、2.63(m、2H)、1.87(m、2H)、1.48(m、1H)、1.38(t、1H)
1 H-NMR (CDCl 3 ) of 3MPO obtained in Example 2
δ = 3.75 (t, 2H), 2.63 (m, 2H), 1.87 (m, 2H), 1.48 (m, 1H), 1.38 (t, 1H)
実施例3
100mLフラスコに、アリルアルコール(5.8g、100mmol)及びジクロロメタン(60mL)を加え、フラスコ内のガス雰囲気を窒素濃度約85体積%及び酸素濃度約15体積%にして密閉した後、フラスコ内容物を50〜60℃に昇温し、チオ−S−酢酸(8.0g、105mmol)を滴下した。滴下終了後、50〜60℃で2時間反応させた。反応終了後、50℃でジクロロメタンを減圧留去することによって、微黄色液体のチオ酢酸S−(3−ヒドロキシプロピル)を12.9g(96mmol、アリルアルコールに対して収率96%)で得た。
Example 3
After adding allyl alcohol (5.8 g, 100 mmol) and dichloromethane (60 mL) to a 100 mL flask and sealing the gas atmosphere in the flask with a nitrogen concentration of about 85% by volume and an oxygen concentration of about 15% by volume, the flask contents were The temperature was raised to 50-60 ° C., and thio-S-acetic acid (8.0 g, 105 mmol) was added dropwise. After completion of dropping, the reaction was carried out at 50 to 60 ° C. for 2 hours. After completion of the reaction, dichloromethane was distilled off under reduced pressure at 50 ° C. to obtain 12.9 g (96 mmol, yield 96% with respect to allyl alcohol) of thioacetic acid S- (3-hydroxypropyl) as a slightly yellow liquid. .
200mLフラスコに、上記のようにして得た全量のチオ酢酸S−(3−ヒドロキシプロピル)(12.9g、96mmol)、98%硫酸(0.96g、9.6mmol)及びメタノール(100mL)を加え、50〜60℃で3時間反応させた。反応終了後にメタノールを留去し、水(30mL)を加え、クロロホルム(50mL×3回)で抽出した。抽出したクロロホルム層を無水硫酸マグネシウム(10g)で脱湿し、無水硫酸マグネシウムをろ過し、クロロホルムを留去することによって得られた粗生成物を単蒸留(15Torr、90℃)することによって、微黄色液体の3MPOを7.8g(84mmol)で得た。3MPOの収率は、中間生成物であるチオ酢酸S−(3−ヒドロキシプロピル)に対して88%であり、出発原料であるアリルアルコールに対して84%であった。 To a 200 mL flask, add the total amount of thioacetic acid S- (3-hydroxypropyl) (12.9 g, 96 mmol), 98% sulfuric acid (0.96 g, 9.6 mmol) and methanol (100 mL) obtained as described above. , Reacted at 50 to 60 ° C. for 3 hours. After completion of the reaction, methanol was distilled off, water (30 mL) was added, and the mixture was extracted with chloroform (50 mL × 3 times). The extracted chloroform layer was dehumidified with anhydrous magnesium sulfate (10 g), the anhydrous magnesium sulfate was filtered, and the crude product obtained by distilling off the chloroform was subjected to simple distillation (15 Torr, 90 ° C.). 7.8 g (84 mmol) of 3MPO as a yellow liquid was obtained. The yield of 3MPO was 88% with respect to the intermediate product S- (3-hydroxypropyl) thioacetate, and 84% with respect to the starting material, allyl alcohol.
実施例3で得られた3MPOの1H−NMR(CDCl3)
δ=3.75(t、2H)、2.63(m、2H)、1.87(m、2H)、1.48(m、1H)、1.38(t、1H)
1 H-NMR (CDCl 3 ) of 3MPO obtained in Example 3
δ = 3.75 (t, 2H), 2.63 (m, 2H), 1.87 (m, 2H), 1.48 (m, 1H), 1.38 (t, 1H)
実施例4
100mLフラスコに、アリルアルコール(5.8g、100mmol)及びクロロホルム(60mL)を加え、フラスコ内のガス雰囲気を窒素濃度約96体積%及び酸素濃度約4体積%にして密閉した後、フラスコ内容物を50〜60℃に昇温し、チオ−S−酢酸(8.0g、105mmol)を滴下した。滴下終了後、50〜60℃で2時間反応させた。反応終了後、50℃でクロロホルムを減圧留去することによって、微黄色液体のチオ酢酸S−(3−ヒドロキシプロピル)を12.6g(94mmol、アリルアルコールに対して収率94%)で得た。
Example 4
After adding allyl alcohol (5.8 g, 100 mmol) and chloroform (60 mL) to a 100 mL flask and sealing the gas atmosphere in the flask with a nitrogen concentration of about 96 vol% and an oxygen concentration of about 4 vol%, the flask contents were The temperature was raised to 50-60 ° C., and thio-S-acetic acid (8.0 g, 105 mmol) was added dropwise. After completion of dropping, the reaction was carried out at 50 to 60 ° C. for 2 hours. After completion of the reaction, chloroform was distilled off under reduced pressure at 50 ° C. to obtain 12.6 g (94 mmol, 94% yield based on allyl alcohol) of thioacetic acid S- (3-hydroxypropyl) as a slightly yellow liquid. .
200mLフラスコに、上記のようにして得た全量のチオ酢酸S−(3−ヒドロキシプロピル)(12.6g、94mmol)、35%塩酸水溶液(0.98g、9.4mmol)及びメタノール(120mL)を加え、50〜60℃で2時間反応させた。反応終了後にメタノール及び塩酸を留去し、単蒸留(15Torr、90℃)することによって、微黄色液体の3MPOを7.2g(78mmol)で得た。3MPOの収率は、中間生成物であるチオ酢酸S−(3−ヒドロキシプロピル)に対して83%であり、出発原料であるアリルアルコールに対して78%であった。 A 200 mL flask was charged with the total amount of S- (3-hydroxypropyl) thioacetate (12.6 g, 94 mmol), 35% aqueous hydrochloric acid (0.98 g, 9.4 mmol) and methanol (120 mL) obtained as described above. In addition, the mixture was reacted at 50 to 60 ° C. for 2 hours. After completion of the reaction, methanol and hydrochloric acid were distilled off, and simple distillation (15 Torr, 90 ° C.) was performed to obtain 7.2 g (78 mmol) of 3MPO as a slightly yellow liquid. The yield of 3MPO was 83% based on the intermediate product S- (3-hydroxypropyl) thioacetate and 78% based on the starting material, allyl alcohol.
実施例4で得られた3MPOの1H−NMR(CDCl3)
δ=3.75(t、2H)、2.63(m、2H)、1.87(m、2H)、1.48(m、1H)、1.38(t、1H)
1 H-NMR (CDCl 3 ) of 3MPO obtained in Example 4
δ = 3.75 (t, 2H), 2.63 (m, 2H), 1.87 (m, 2H), 1.48 (m, 1H), 1.38 (t, 1H)
実施例5
100mLフラスコに、アリルアルコール(5.8g、100mmol)を加え、フラスコ内のガス雰囲気を窒素濃度約96体積%及び酸素濃度約4体積%にして密閉した後、フラスコ内容物を50〜60℃に昇温し、チオ−S−酢酸(8.0g、105mmol)を滴下した。滴下終了後、50〜60℃で2時間反応させた。反応終了後、残存するアリルアルコール及びチオ−S−酢酸を留去することによって、微黄色液体のチオ酢酸S−(3−ヒドロキシプロピル)を11.4g(85mmol、アリルアルコールに対して収率85%)で得た。
Example 5
After adding allyl alcohol (5.8 g, 100 mmol) to a 100 mL flask and sealing the gas atmosphere in the flask with a nitrogen concentration of about 96% by volume and an oxygen concentration of about 4% by volume, the flask contents were brought to 50-60 ° C. The temperature was raised, and thio-S-acetic acid (8.0 g, 105 mmol) was added dropwise. After completion of dropping, the reaction was carried out at 50 to 60 ° C. for 2 hours. After completion of the reaction, the remaining allyl alcohol and thio-S-acetic acid were distilled off to obtain 11.4 g (85 mmol, 85% yield of allyl alcohol) of thioacetic acid S- (3-hydroxypropyl) as a slightly yellow liquid. %).
200mLフラスコに、上記のようにして得た全量のチオ酢酸S−(3−ヒドロキシプロピル)(11.4g、85mmol)、35%塩酸水溶液(0.88g、8.5mmol)及びメタノール(120mL)を加え、50〜60℃で2時間反応させた。反応終了後にメタノール及び塩酸を留去し、単蒸留(15Torr、90℃)することによって、微黄色液体の3MPOを6.7g(72mmol)で得た。3MPOの収率は、中間生成物であるチオ酢酸S−(3−ヒドロキシプロピル)に対して85%であり、出発原料であるアリルアルコールに対して72%であった。 A 200 mL flask was charged with the entire amount of thioacetic acid S- (3-hydroxypropyl) (11.4 g, 85 mmol), 35% aqueous hydrochloric acid (0.88 g, 8.5 mmol) and methanol (120 mL) obtained as described above. In addition, the mixture was reacted at 50 to 60 ° C. for 2 hours. After completion of the reaction, methanol and hydrochloric acid were distilled off, and simple distillation (15 Torr, 90 ° C.) was performed to obtain 6.7 g (72 mmol) of 3MPO as a slightly yellow liquid. The yield of 3MPO was 85% with respect to S- (3-hydroxypropyl) thioacetate as an intermediate product, and 72% with respect to allyl alcohol as a starting material.
実施例5で得られた3MPOの1H−NMR(CDCl3)
δ=3.75(t、2H)、2.63(m、2H)、1.87(m、2H)、1.48(m、1H)、1.38(t、1H)
1 H-NMR (CDCl 3 ) of 3MPO obtained in Example 5
δ = 3.75 (t, 2H), 2.63 (m, 2H), 1.87 (m, 2H), 1.48 (m, 1H), 1.38 (t, 1H)
実施例6
100mLフラスコに、アリルアルコール(5.8g、100mmol)及びクロロホルム(60mL)を加え、フラスコ内のガス雰囲気を窒素濃度約85体積%及び酸素濃度約15体積%にして密閉した後、フラスコ内容物を50〜60℃に昇温し、チオ−S−プロピオン酸(9.9g、110mmol)を滴下した。滴下終了後、50〜60℃で3時間反応させた。反応終了後、50℃でクロロホルムを減圧留去することによって、微黄色液体のチオプロピオン酸S−(3−ヒドロキシプロピル)を13.5g(91mmol、アリルアルコールに対して収率91%)で得た。
Example 6
After adding allyl alcohol (5.8 g, 100 mmol) and chloroform (60 mL) to a 100 mL flask and sealing the gas atmosphere in the flask with a nitrogen concentration of about 85 vol% and an oxygen concentration of about 15 vol%, the flask contents were The temperature was raised to 50-60 ° C., and thio-S-propionic acid (9.9 g, 110 mmol) was added dropwise. After completion of dropping, the reaction was carried out at 50 to 60 ° C. for 3 hours. After completion of the reaction, chloroform was distilled off under reduced pressure at 50 ° C. to obtain 13.5 g (91 mmol, 91% yield with respect to allyl alcohol) of thiopropionic acid S- (3-hydroxypropyl) as a slightly yellow liquid. It was.
200mLフラスコに、上記のようにして得た全量のチオプロピオン酸S−(3−ヒドロキシプロピル)(13.5g、91mmol)、ヒドラジン一水和物(5.0g、100mmol)及びメタノール(100mL)を加え、20〜30℃で1時間反応させた。反応終了後にメタノールを留去し、水(30mL)を加え、クロロホルム(50mL×3回)で抽出した。抽出したクロロホルム層を無水硫酸マグネシウム(10g)で脱湿し、無水硫酸マグネシウムをろ過し、クロロホルムを留去することによって得られた粗生成物を単蒸留(15Torr、90℃)することによって、微黄色液体の3MPOを6.7g(72mmol)で得た。3MPOの収率は、中間生成物であるチオプロピオン酸S−(3−ヒドロキシプロピル)に対して80%であり、出発原料であるアリルアルコールに対して72%であった。 A 200 mL flask was charged with the total amount of thiopropionic acid S- (3-hydroxypropyl) (13.5 g, 91 mmol), hydrazine monohydrate (5.0 g, 100 mmol) and methanol (100 mL) obtained as described above. In addition, the mixture was reacted at 20 to 30 ° C. for 1 hour. After completion of the reaction, methanol was distilled off, water (30 mL) was added, and the mixture was extracted with chloroform (50 mL × 3 times). The extracted chloroform layer was dehumidified with anhydrous magnesium sulfate (10 g), the anhydrous magnesium sulfate was filtered, and the crude product obtained by distilling off the chloroform was subjected to simple distillation (15 Torr, 90 ° C.). 6.7 g (72 mmol) of 3MPO as a yellow liquid was obtained. The yield of 3MPO was 80% with respect to the intermediate product S- (3-hydroxypropyl) thiopropionate, and 72% with respect to the starting material, allyl alcohol.
実施例6で得られた3MPOの1H−NMR(CDCl3)
δ=3.75(t、2H)、2.63(m、2H)、1.87(m、2H)、1.48(m、1H)、1.38(t、1H)
1 H-NMR (CDCl 3 ) of 3MPO obtained in Example 6
δ = 3.75 (t, 2H), 2.63 (m, 2H), 1.87 (m, 2H), 1.48 (m, 1H), 1.38 (t, 1H)
実施例1〜6の条件及び3MPOの収率を下記表1に示す。本発明の製造方法は、従来の上記製法(a)と異なり発火性の水素化アルミニウムリチウムを使用せずに、3MPOを製造できる。また本発明の製造方法の3MPOの収率(出発原料であるアリルアルコール基準)は70〜84%であり、従来の上記製法(b)に対して大幅に向上している。 The conditions of Examples 1 to 6 and the yield of 3MPO are shown in Table 1 below. Unlike the conventional production method (a), the production method of the present invention can produce 3MPO without using ignitable lithium aluminum hydride. Further, the yield of 3MPO (based on allyl alcohol as a starting material) in the production method of the present invention is 70 to 84%, which is a significant improvement over the conventional production method (b).
本発明の製造方法によれば、発火性の水素化アルミニウムリチウムを使用せず、且つ高収率で3−メルカプト−1−プロパノール(3MPO)を得ることができる。3MPOは、医薬品、農薬、電子材料などの製造用中間体として有用である。 According to the production method of the present invention, 3-mercapto-1-propanol (3MPO) can be obtained in high yield without using ignitable lithium aluminum hydride. 3MPO is useful as an intermediate for production of pharmaceuticals, agricultural chemicals, electronic materials and the like.
Claims (3)
アリルアルコールに式(1)で表される化合物を付加させて式(2)で表される化合物を合成し、次いで式(2)で表される化合物を加水分解して3−メルカプト−1−プロパノールを合成することを特徴とする製造方法。
A compound represented by formula (1) is added to allyl alcohol to synthesize a compound represented by formula (2), and then the compound represented by formula (2) is hydrolyzed to give 3-mercapto-1- A production method comprising synthesizing propanol.
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Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2398479A (en) * | 1941-03-28 | 1946-04-16 | Shell Dev | Preparation of organic sulphur compounds |
US3069472A (en) * | 1960-08-23 | 1962-12-18 | Pennsalt Chemical Corp | Novel process for preparation of mercaptans by catalytic cleavage of sulfides |
JPS545951A (en) * | 1977-06-09 | 1979-01-17 | Rohm & Haas | O * ssdialkyl o*s** sulfonyloxy *thio* phenylphosphorothioate and phosphorodi *tri* thioate |
JPS55139351A (en) * | 1979-04-14 | 1980-10-31 | Kinkidaigaku | Preparation of optically active thiol by radical reaction of vinyl ester of optically active alcohol with thioacetic acid |
JPS56161366A (en) * | 1972-04-06 | 1981-12-11 | Polak Frutal Works | Manufacture of novel mercapto alcohol |
JPH01226866A (en) * | 1988-03-08 | 1989-09-11 | Wako Pure Chem Ind Ltd | Mercaptomethylation |
JP2005035968A (en) * | 2003-06-24 | 2005-02-10 | Idemitsu Kosan Co Ltd | Alicyclic dithiol |
JP2005075746A (en) * | 2003-08-29 | 2005-03-24 | Nippon Paint Co Ltd | Method for producing thiol compound |
JP2006083154A (en) * | 2003-12-25 | 2006-03-30 | Takeda Chem Ind Ltd | 3-(4-benzyloxyphenyl)propanoic acid derivative |
JP2009114077A (en) * | 2007-11-01 | 2009-05-28 | Toyo Kasei Kogyo Co Ltd | Method for producing alkylcarbonylthio-substituted alkane |
-
2009
- 2009-09-30 JP JP2009227316A patent/JP5573079B2/en not_active Expired - Fee Related
-
2010
- 2010-08-09 WO PCT/JP2010/063785 patent/WO2011040131A1/en active Application Filing
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2398479A (en) * | 1941-03-28 | 1946-04-16 | Shell Dev | Preparation of organic sulphur compounds |
US3069472A (en) * | 1960-08-23 | 1962-12-18 | Pennsalt Chemical Corp | Novel process for preparation of mercaptans by catalytic cleavage of sulfides |
JPS56161366A (en) * | 1972-04-06 | 1981-12-11 | Polak Frutal Works | Manufacture of novel mercapto alcohol |
JPS545951A (en) * | 1977-06-09 | 1979-01-17 | Rohm & Haas | O * ssdialkyl o*s** sulfonyloxy *thio* phenylphosphorothioate and phosphorodi *tri* thioate |
JPS55139351A (en) * | 1979-04-14 | 1980-10-31 | Kinkidaigaku | Preparation of optically active thiol by radical reaction of vinyl ester of optically active alcohol with thioacetic acid |
JPH01226866A (en) * | 1988-03-08 | 1989-09-11 | Wako Pure Chem Ind Ltd | Mercaptomethylation |
JP2005035968A (en) * | 2003-06-24 | 2005-02-10 | Idemitsu Kosan Co Ltd | Alicyclic dithiol |
JP2005075746A (en) * | 2003-08-29 | 2005-03-24 | Nippon Paint Co Ltd | Method for producing thiol compound |
JP2006083154A (en) * | 2003-12-25 | 2006-03-30 | Takeda Chem Ind Ltd | 3-(4-benzyloxyphenyl)propanoic acid derivative |
JP2009114077A (en) * | 2007-11-01 | 2009-05-28 | Toyo Kasei Kogyo Co Ltd | Method for producing alkylcarbonylthio-substituted alkane |
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