JP5748752B2 - Method for producing cyanohydrin - Google Patents
Method for producing cyanohydrin Download PDFInfo
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- JP5748752B2 JP5748752B2 JP2012520426A JP2012520426A JP5748752B2 JP 5748752 B2 JP5748752 B2 JP 5748752B2 JP 2012520426 A JP2012520426 A JP 2012520426A JP 2012520426 A JP2012520426 A JP 2012520426A JP 5748752 B2 JP5748752 B2 JP 5748752B2
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- 238000004519 manufacturing process Methods 0.000 title claims description 50
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 92
- 238000006243 chemical reaction Methods 0.000 claims description 76
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 49
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 44
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 30
- 239000007853 buffer solution Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 15
- 150000007524 organic acids Chemical class 0.000 claims description 12
- 150000001299 aldehydes Chemical class 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 239000000872 buffer Substances 0.000 claims description 6
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 20
- LTYRAPJYLUPLCI-UHFFFAOYSA-N glycolonitrile Chemical compound OCC#N LTYRAPJYLUPLCI-UHFFFAOYSA-N 0.000 description 16
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000011259 mixed solution Substances 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000008098 formaldehyde solution Substances 0.000 description 5
- 229940023144 sodium glycolate Drugs 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- 125000002877 alkyl aryl group Chemical group 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- -1 ethylphenyl group Chemical group 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000002728 pyrethroid Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000011437 continuous method Methods 0.000 description 2
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- NNICRUQPODTGRU-UHFFFAOYSA-N mandelonitrile Chemical compound N#CC(O)C1=CC=CC=C1 NNICRUQPODTGRU-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical group CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical class CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 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
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000006267 biphenyl group Chemical group 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
- 230000003139 buffering effect Effects 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
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 230000003301 hydrolyzing effect Effects 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
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- WOFDVDFSGLBFAC-UHFFFAOYSA-N lactonitrile Chemical compound CC(O)C#N WOFDVDFSGLBFAC-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 159000000001 potassium salts Chemical class 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
- 238000011403 purification operation Methods 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/08—Preparation of carboxylic acid nitriles by addition of hydrogen cyanide or salts thereof to unsaturated compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、シアノヒドリンの製造方法に関する。 The present invention relates to a method for producing cyanohydrin.
シアノヒドリン化合物は、例えば、医薬有効物質、ビタミン又はピレスロイド化合物等の生理活性物質を製造するために多く使用されるα−ヒドロキシカルボン酸化合物、α−ヒドロキシケトン化合物又はβ−アミノアルコール化合物等の合成に用いる中間体として重要である。 Cyanohydrin compounds are used for the synthesis of α-hydroxycarboxylic acid compounds, α-hydroxyketone compounds, β-aminoalcohol compounds and the like that are often used to produce physiologically active substances such as pharmaceutically active substances, vitamins, and pyrethroid compounds. It is important as an intermediate to be used.
シアノヒドリン化合物としては、グリコロニトリルが最も一般的であり、その製造方法としては、例えば、特許文献１〜４に記載の方法が開示されている。 As the cyanohydrin compound, glycolonitrile is the most common, and as its production method, for example, methods described in Patent Documents 1 to 4 are disclosed.
特許文献１には、触媒量の酢酸ナトリウムを溶解したホルマリン液に青酸を液温１５〜３０℃で、必要ならば、酢酸または酢酸ナトリウムを添加しながらｐＨを４．８〜６．０に保って滴下し同条件下で反応を行うことが記載されている。 In Patent Document 1, in a formalin solution in which a catalytic amount of sodium acetate is dissolved, the pH is kept at 4.8 to 6.0 while adding acetic acid or sodium acetate at a liquid temperature of 15 to 30 ° C., if necessary. And the reaction is carried out under the same conditions.
また、特許文献２には、水性媒体中にてホルムアルデヒドと青酸とを反応させてグリコロニトリルを製造する際、反応系に少量の酸性亜硫酸イオンを存在せしめることを特徴とするグリコロニトリルの製造方法が記載されており、具体的には、亜硫酸ソーダ水溶液を反応液のｐＨが４．０〜５．０となるように調節しつつ適宜反応槽に供給することが記載されている。 Patent Document 2 discloses the production of glycolonitrile characterized in that a small amount of acidic sulfite ion is present in the reaction system when formaldehyde and hydrocyanic acid are reacted in an aqueous medium to produce glycolonitrile. A method is described, and specifically, it is described that an aqueous sodium sulfite solution is appropriately supplied to a reaction vessel while adjusting the pH of the reaction solution to be 4.0 to 5.0.
また、特許文献３には、青酸とホルムアルデヒドとを水性媒体中で反応させてグリコロニトリルを製造する方法において、反応帯域の温度Ｔ（℃）、反応液のｐＨをＰとしたとき、ＴとＰの積が１５５〜２４０であることを特徴とするグリコロニトリルの製造方法が記載されており、具体的には、例えば、ｐＨを低くするためには、少量の二酸化イオウ、亜硫酸、硫酸などを添加し、ｐＨを高くする場合は、少量の亜硫酸ソーダ、苛性ソーダなどを添加する旨記載されている。 Further, in Patent Document 3, in a method for producing glycolonitrile by reacting hydrocyanic acid and formaldehyde in an aqueous medium, when T is the reaction zone temperature T (° C.) and P is the pH of the reaction solution, T and A process for producing glycolonitrile characterized in that the product of P is 155 to 240 is described. Specifically, for example, in order to lower the pH, a small amount of sulfur dioxide, sulfurous acid, sulfuric acid, etc. Is added to increase the pH, a small amount of sodium sulfite or caustic soda is added.
さらに、特許文献４には、グリコロニトリルの調製方法であって、（ａ）測定可能な時間に約９０℃〜約１５０℃の温度に加熱される水性ホルムアルデヒドを供給する流れを提供するステップと、（ｂ）（ａ）の加熱された水性物を供給する流れをグリコロニトリル合成に適切な温度でシアン化水素を接触させ、それによってグリコロニトリルが製造されるステップとを含むことを特徴とする方法が記載されている。そして、グリコルニトリル合成反応室におけるｐＨは約３〜約１０、好ましくは約５〜約８とすることが記載されている。 Further, Patent Document 4 provides a method for preparing glycolonitrile, comprising: (a) providing a stream for supplying aqueous formaldehyde heated to a temperature of about 90 ° C. to about 150 ° C. for a measurable time; (B) contacting the heated aqueous feed stream of (a) with hydrogen cyanide at a temperature suitable for glycolonitrile synthesis, whereby glycolonitrile is produced. A method is described. It is described that the pH in the glycolonitrile synthesis reaction chamber is about 3 to about 10, preferably about 5 to about 8.
しかしながら、特許文献１〜３に記載の方法は、反応進行中に適宜ｐＨ調整を行う必要があり、作業効率が悪いという問題があった。また、特許文献４に記載の方法では、シアノヒドリンの生成率が、必ずしも高くない場合があった。さらに、特許文献１〜４に記載の方法では、ホルムアルデヒドと青酸との反応速度を精度良く制御することが困難であった。 However, the methods described in Patent Documents 1 to 3 have a problem that the pH needs to be adjusted appropriately during the progress of the reaction, resulting in poor working efficiency. Moreover, in the method described in Patent Document 4, the production rate of cyanohydrin is not always high. Furthermore, in the methods described in Patent Documents 1 to 4, it is difficult to accurately control the reaction rate between formaldehyde and hydrocyanic acid.
そこで本発明は、反応進行中にｐＨの調整を行わなくとも、カルボニル化合物と青酸との反応速度を精度良く制御することができ、且つ、十分に高い生成率でシアノヒドリンを生成することが可能な、シアノヒドリンの製造方法を提供する。 Therefore, the present invention can accurately control the reaction rate between the carbonyl compound and hydrocyanic acid without adjusting the pH during the reaction, and can produce cyanohydrin at a sufficiently high production rate. A method for producing cyanohydrin is provided.
すなわち本発明は、カルボニル化合物と、青酸とを、ｐＨが７未満の緩衝液中で反応させてシアノヒドリンを得る、シアノヒドリンの製造方法を提供する。 That is, the present invention provides a method for producing cyanohydrin, in which a carbonyl compound and hydrocyanic acid are reacted in a buffer solution having a pH of less than 7 to obtain cyanohydrin.
通常、青酸とカルボニル化合物との反応速度はｐＨに依存し、当該ｐＨは反応の進行に伴って変化する。従来の製造方法では、ｐＨの変化に併せて適宜ｐＨの調整を行うが、このような方法ではｐＨを精度良く一定に保つことが困難であり、このことが反応速度の制御を困難にしている一因と考えられる。これに対して、本発明に係る製造方法では、緩衝液中で反応を進行させるため、ｐＨの調整を行わずとも反応進行中のｐＨが一定に保持される。そのため、本発明においては、カルボニル化合物と青酸との反応速度を精度良く制御することができる。 Usually, the reaction rate between hydrocyanic acid and a carbonyl compound depends on the pH, and the pH changes as the reaction proceeds. In the conventional production method, the pH is appropriately adjusted in accordance with the change in pH. However, in such a method, it is difficult to keep the pH accurately and constant, which makes it difficult to control the reaction rate. This is considered to be a cause. In contrast, in the production method according to the present invention, the reaction proceeds in a buffer solution, and therefore the pH during the reaction is kept constant without adjusting the pH. Therefore, in the present invention, the reaction rate between the carbonyl compound and hydrocyanic acid can be controlled with high accuracy.
さらに、本発明によれば、高い生成率でシアノヒドリンを製造することができる。この理由は必ずしも明らかではないが、本発明では緩衝液中で反応を行うため、ｐＨの変動による生成率の低下が生じ難く、高い生成率を達成できるものと考えられる。 Furthermore, according to the present invention, cyanohydrin can be produced with a high production rate. The reason for this is not necessarily clear, but in the present invention, since the reaction is carried out in a buffer solution, it is unlikely that the production rate is lowered due to fluctuations in pH, and a high production rate can be achieved.
本発明はまた、カルボニル化合物を含有し且つｐＨが７未満である緩衝液を、所定温度範囲に保持しつつ、上記緩衝液に青酸を添加して、上記緩衝液中で上記カルボニル化合物と上記青酸とを反応させてシアノヒドリンを得る、シアノヒドリンの製造方法を提供する。このような製造方法によれば、ｐＨの調整を行わずともカルボニル化合物と青酸との反応速度を精度良く制御することができ、且つ、高い生成率でシアノヒドリンを製造することができる。 The present invention also includes adding a hydrocyanic acid to the buffer solution while maintaining a buffer solution containing a carbonyl compound and having a pH of less than 7 within a predetermined temperature range, and the carbonyl compound and the hydrocyanic acid in the buffer solution. The present invention provides a method for producing cyanohydrin in which cyanohydrin is obtained by reacting with. According to such a production method, the reaction rate between the carbonyl compound and hydrocyanic acid can be accurately controlled without adjusting the pH, and cyanohydrin can be produced with a high production rate.
本発明において、上記緩衝液は、弱酸及び該弱酸の塩を含有することが好ましい。また、上記緩衝液は、有機酸及び該有機酸の塩を含有することが好ましい。このような緩衝液によれば、カルボニル化合物と青酸との反応におけるｐＨの変動を一層抑制することができる。そのため、本発明の効果がより確実に奏されるようになる。 In the present invention, the buffer solution preferably contains a weak acid and a salt of the weak acid. The buffer solution preferably contains an organic acid and a salt of the organic acid. According to such a buffer solution, fluctuations in pH in the reaction between the carbonyl compound and hydrocyanic acid can be further suppressed. Therefore, the effect of the present invention is more reliably achieved.
上記有機酸は、シアノヒドリンを加水分解させたときに生成するα−ヒドロキシカルボン酸と同種のα−ヒドロキシカルボン酸であることが好ましい。このような有機酸を用いることにより、生成したシアノヒドリンを更に加水分解してα−ヒドロキシカルボン酸を得る場合に、精製が容易となる。また、シアノヒドリンの生成率が一層向上するようになる。 The organic acid is preferably an α-hydroxycarboxylic acid of the same type as the α-hydroxycarboxylic acid produced when cyanohydrin is hydrolyzed. By using such an organic acid, purification is facilitated when the produced cyanohydrin is further hydrolyzed to obtain an α-hydroxycarboxylic acid. In addition, the production rate of cyanohydrin is further improved.
また、上記有機酸は、グリコール酸であることが好ましい。グリコール酸及びグリコール酸の塩を含有する緩衝液によれば、ｐＨの変動を一層抑制することができるとともに、シアノヒドリンの生成率が一層向上するようになる。 The organic acid is preferably glycolic acid. According to the buffer solution containing glycolic acid and a salt of glycolic acid, it is possible to further suppress pH fluctuations and to further improve the production rate of cyanohydrin.
上記カルボニル化合物は、アルデヒド類であることが好ましく、ホルムアルデヒドであることがより好ましい。このようなカルボニル化合物から得られるシアノヒドリンは、医薬有効物質、ビタミン又はピレスロイド化合物等の生理活性物質を製造するための中間体として非常に有用である。 The carbonyl compound is preferably an aldehyde, and more preferably formaldehyde. Cyanohydrins obtained from such carbonyl compounds are very useful as intermediates for producing physiologically active substances such as pharmaceutically active substances, vitamins or pyrethroid compounds.
本発明によれば、反応進行中にｐＨの調整を行わなくとも、カルボニル化合物と青酸との反応速度を精度良く制御することができ、且つ、十分に高い生成率でシアノヒドリンを生成することが可能な、シアノヒドリンの製造方法を提供することができる。 According to the present invention, the reaction rate between the carbonyl compound and hydrocyanic acid can be accurately controlled without adjusting the pH during the reaction, and cyanohydrin can be produced at a sufficiently high production rate. In addition, a method for producing cyanohydrin can be provided.
本発明のシアノヒドリンの製造方法の好適な実施形態について以下に説明する。 A preferred embodiment of the method for producing cyanohydrin of the present invention will be described below.
本実施形態に係るシアノヒドリンの製造方法は、カルボニル化合物と、青酸とを、ｐＨが７未満の緩衝液中で反応させてシアノヒドリンを得るものである。 In the method for producing cyanohydrin according to this embodiment, a carbonyl compound and hydrocyanic acid are reacted in a buffer solution having a pH of less than 7 to obtain cyanohydrin.
ここで、カルボニル化合物とは、カルボニル基を有する化合物であり、例えば、下記式（１）で表される化合物が挙げられる。 Here, the carbonyl compound is a compound having a carbonyl group, and examples thereof include a compound represented by the following formula (1).
式中、Ｒ１及びＲ２は、それぞれ独立に、水素原子、炭素数１〜６のアルキル基、炭素数６〜１４のアリール基又は炭素数７〜９のアルキルアリール基を示す。In the formula, R 1 and R 2 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an aryl group having 6 to 14 carbon atoms, or an alkylaryl group having 7 to 9 carbon atoms.
炭素数１〜６のアルキル基としては、例えば、メチル基、エチル基、プロピル基、ブチル基、ペンチル基、ヘキシル基が挙げられる。これらのアルキル基は、直鎖状であっても分岐状であっても環を形成していてもよい。 Examples of the alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group. These alkyl groups may be linear, branched, or form a ring.
炭素数６〜１４のアリール基としては、フェニル基、トリル基、キシリル基、ナフチル基、ビフェニル基、アントリル基等が挙げられる。 Examples of the aryl group having 6 to 14 carbon atoms include phenyl group, tolyl group, xylyl group, naphthyl group, biphenyl group, and anthryl group.
炭素数７〜９のアルキルアリール基としては、ベンジル基、エチルフェニル基、シンナミル基等が挙げられる。 Examples of the alkylaryl group having 7 to 9 carbon atoms include benzyl group, ethylphenyl group, cinnamyl group and the like.
カルボニル化合物として、具体的には、アセトン（Ｒ１及びＲ２がいずれもメチル基である化合物）、メチルエチルケトン（Ｒ１及びＲ２の一方がメチル基、他方がエチル基である化合物）、イソブチルメチルケトン（Ｒ１及びＲ２の一方がメチル基、他方がイソブチル基である化合物）等のケトン類；ホルムアルデヒド（Ｒ１及びＲ２がいずれも水素原子である化合物）、アセトアルデヒド（Ｒ１及びＲ２の一方が水素原子、他方がメチル基である化合物）、プロピオンアルデヒド（Ｒ１及びＲ２の一方が水素原子、他方がエチル基である化合物）、ベンズアルデヒド（Ｒ１及びＲ２の一方が水素原子、他方がフェニル基である化合物）等のアルデヒド類；等が挙げられる。Specific examples of the carbonyl compound include acetone (a compound in which R 1 and R 2 are both methyl groups), methyl ethyl ketone (a compound in which one of R 1 and R 2 is a methyl group, and the other is an ethyl group), isobutylmethyl Ketones such as ketones (compounds in which one of R 1 and R 2 is a methyl group and the other is an isobutyl group); formaldehyde (a compound in which both R 1 and R 2 are hydrogen atoms), acetaldehyde (R 1 and R 2 In which one of them is a hydrogen atom and the other is a methyl group), propionaldehyde (a compound in which one of R 1 and R 2 is a hydrogen atom and the other is an ethyl group), benzaldehyde ( one of R 1 and R 2 is a hydrogen atom) , Aldehydes such as a compound in which the other is a phenyl group;
式（１）においては、Ｒ１及びＲ２がいずれも水素原子ではない化合物がケトン類であり、Ｒ１及びＲ２のうち少なくとも一つが水素原子である化合物がアルデヒド類である。In the formula (1), compounds in which R 1 and R 2 are not hydrogen atoms are ketones, and compounds in which at least one of R 1 and R 2 is a hydrogen atom are aldehydes.
カルボニル化合物としては、アルデヒド類が好ましい。すなわち、式（１）においては、Ｒ１及びＲ２のうち少なくとも一つが水素原子であることが好ましい。アルデヒド類は、ケトン類と比較して、青酸と効率良く反応しやすく、より高い生成率でシアノヒドリンを製造することができる。また、アルデヒド類のうち、グリシンやヒダントイン等の製造中間体として有用なグリコロニトリルを製造できる観点からは、ホルムアルデヒドが好ましい。As the carbonyl compound, aldehydes are preferable. That is, in Formula (1), it is preferable that at least one of R 1 and R 2 is a hydrogen atom. Aldehydes easily react with hydrocyanic acid more efficiently than ketones, and can produce cyanohydrin at a higher production rate. Of the aldehydes, formaldehyde is preferable from the viewpoint of producing glycolonitrile useful as a production intermediate for glycine, hydantoin, and the like.
カルボニル化合物は、例えば、水溶液として反応に供することができる。すなわち、カルボニル化合物がホルムアルデヒドである場合、ホルムアルデヒド水溶液として反応に供することができる。 The carbonyl compound can be subjected to the reaction as an aqueous solution, for example. That is, when the carbonyl compound is formaldehyde, it can be subjected to the reaction as an aqueous formaldehyde solution.
青酸は、気体、液体又は水溶液等、任意の形態で反応に供することができ、液体又は水溶液として供することが好ましい。 Cyanic acid can be subjected to the reaction in any form such as gas, liquid or aqueous solution, and is preferably provided as a liquid or aqueous solution.
反応に供する青酸の量は、シアノヒドリンの生成率を向上させる観点から、カルボニル化合物の総量に対して、モル数で１〜１．２倍が好ましく、１〜１．１倍がより好ましい。 From the viewpoint of improving the production rate of cyanohydrin, the amount of hydrocyanic acid used for the reaction is preferably 1 to 1.2 times, more preferably 1 to 1.1 times in terms of moles, relative to the total amount of carbonyl compound.
カルボニル化合物と青酸との反応により得られるシアノヒドリンは、例えば、下記式（２）で表される化合物である。 Cyanohydrin obtained by the reaction of a carbonyl compound and hydrocyanic acid is, for example, a compound represented by the following formula (2).
式中、Ｒ１及びＲ２は、式（１）におけるＲ１及びＲ２と同義である。Wherein, R 1 and R 2 have the same meanings as R 1 and R 2 in the formula (1).
具体的には、例えば、ホルムアルデヒドからはグリコロニトリル（別名：ヒドロキシアセトニトリル、式（２）におけるＲ１及びＲ２がいずれも水素原子である化合物）、アセトンからはアセトンシアノヒドリン（別名：α−ヒドロキシイソブチロニトリル、式（２）におけるＲ１及びＲ２がいずれもメチル基である化合物）、ベンズアルデヒドからはマンデロニトリル（式（２）におけるＲ１及びＲ２の一方が水素原子、他方がフェニル基である化合物）をそれぞれ得ることができる。Specifically, for example, formaldehyde is glycolonitrile (also known as hydroxyacetonitrile, a compound in which R 1 and R 2 in formula (2) are both hydrogen atoms), and acetone is acetone cyanohydrin (also known as α-hydroxy). Isobutyronitrile, a compound in which R 1 and R 2 in formula (2) are both methyl groups), and benzaldehyde from mandelonitrile ( one of R 1 and R 2 in formula (2) is a hydrogen atom and the other is Each compound is a phenyl group.
カルボニル化合物と青酸との反応は、触媒の存在下で行われることが好ましい。触媒としては、シアン化ナトリウム、シアン化カリウム等が挙げられる。 The reaction between the carbonyl compound and hydrocyanic acid is preferably carried out in the presence of a catalyst. Examples of the catalyst include sodium cyanide and potassium cyanide.
触媒の使用量は、反応に供するカルボニル化合物の総量に対して、０．０１〜０．５モル％であることが好ましく、０．０５〜０．１モル％であることがより好ましい。 The amount of catalyst used is preferably 0.01 to 0.5 mol%, more preferably 0.05 to 0.1 mol%, based on the total amount of carbonyl compounds to be subjected to the reaction.
緩衝液とは、緩衝作用のある溶液、すなわち、所定量の酸又は塩基を添加してもそのｐＨの変化が小さい溶液をいう。緩衝液は、好適には、弱酸及び弱酸の塩を含有する水溶液であり、より好適には、有機酸及び有機酸の塩を含有する水溶液である。 The buffer solution means a solution having a buffering action, that is, a solution whose change in pH is small even when a predetermined amount of acid or base is added. The buffer is preferably an aqueous solution containing a weak acid and a weak acid salt, and more preferably an aqueous solution containing an organic acid and an organic acid salt.
上記の弱酸としては、酢酸、蟻酸、グリコール酸、クエン酸、酒石酸、マンデル酸、グルタル酸、リンゴ酸、マロン酸、フタル酸、コハク酸等の有機酸；リン酸、ホウ酸等の無機酸；等が挙げられ、これらのうち有機酸が好ましい。 Examples of the weak acid include organic acids such as acetic acid, formic acid, glycolic acid, citric acid, tartaric acid, mandelic acid, glutaric acid, malic acid, malonic acid, phthalic acid, and succinic acid; inorganic acids such as phosphoric acid and boric acid; Of these, organic acids are preferred.
上記の弱酸の塩としては、上記の弱酸の、ナトリウム塩、カリウム塩等のアルカリ金属塩；マグネシウム塩、バリウム塩等のアルカリ土類金属塩；等が挙げられる。 Examples of the weak acid salts include alkali metal salts such as sodium salts and potassium salts of the above weak acids; alkaline earth metal salts such as magnesium salts and barium salts.
また、上記の弱酸としては、α−ヒドロキシカルボン酸が好ましい。α−ヒドロキシカルボン酸と、α−ヒドロキシカルボン酸の塩と、を含有する緩衝液によれば、シアノヒドリンがより高い生成率で得られる。 Moreover, as said weak acid, alpha-hydroxycarboxylic acid is preferable. According to the buffer containing α-hydroxycarboxylic acid and a salt of α-hydroxycarboxylic acid, cyanohydrin can be obtained at a higher production rate.
α−ヒドロキシカルボン酸としては、例えば、下記式（３）で表される化合物が挙げられる。 As alpha-hydroxycarboxylic acid, the compound represented by following formula (3) is mentioned, for example.
式中、Ｒ３及びＲ４は、それぞれ独立に、水素原子、炭素数１〜６のアルキル基、炭素数６〜１４のアリール基又は炭素数７〜９のアルキルアリール基を示す。また、炭素数１〜６のアルキル基、炭素数６〜１４のアリール基及び炭素数７〜９のアルキルアリール基としては、それぞれ上記と同様の基が例示される。In the formula, R 3 and R 4 each independently represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an aryl group having 6 to 14 carbon atoms, or an alkylaryl group having 7 to 9 carbon atoms. Moreover, as a C1-C6 alkyl group, a C6-C14 aryl group, and a C7-C9 alkylaryl group, the group similar to the above is illustrated, respectively.
ところで、シアノヒドリンは、例えば、微生物を用いた加水分解反応によりα−ヒドロキシカルボン酸を生成する。このようにして生成されたα−ヒドロキシカルボン酸は、医薬有効物質、ビタミン又はピレスロイド化合物等の生理活性物質を製造するために多く使用され、有用である。 By the way, cyanohydrin produces | generates (alpha) -hydroxycarboxylic acid, for example by the hydrolysis reaction using microorganisms. The α-hydroxycarboxylic acid thus produced is often used and useful for producing a physiologically active substance such as a pharmaceutically active substance, a vitamin or a pyrethroid compound.
そこで、上記の弱酸として、製造されるシアノヒドリンを加水分解させたときに生成するα−ヒドロキシカルボン酸と同種のα−ヒドロキシカルボン酸を用いると、反応後にシアノヒドリンの精製を行うことなく、上述した加水分解反応に供することができる。このとき、α−ヒドロキシカルボン酸の存在によって、微生物を用いた加水分解反応は阻害されず、加水分解反応により生じるα−ヒドロキシカルボン酸と同一のものであるため精製操作を阻害することもない。このような観点から、上記の弱酸としては、製造されるシアノヒドリンを加水分解させたときに生成するα−ヒドロキシカルボン酸と同種のα−ヒドロキシカルボン酸を用いることが好ましい。このようなα−ヒドロキシカルボン酸は、下記式（４）で表すことができる。 Therefore, when the α-hydroxycarboxylic acid of the same kind as the α-hydroxycarboxylic acid produced when hydrolyzing the produced cyanohydrin is used as the weak acid, the above-mentioned hydrolysis can be performed without purifying the cyanohydrin after the reaction. It can be subjected to a decomposition reaction. At this time, the presence of the α-hydroxycarboxylic acid does not inhibit the hydrolysis reaction using the microorganism, and it is the same as the α-hydroxycarboxylic acid produced by the hydrolysis reaction, and therefore does not inhibit the purification operation. From such a viewpoint, it is preferable to use the same kind of α-hydroxycarboxylic acid as the α-hydroxycarboxylic acid produced when the produced cyanohydrin is hydrolyzed as the weak acid. Such α-hydroxycarboxylic acid can be represented by the following formula (4).
式中、Ｒ１及びＲ２は、式（１）におけるＲ１及びＲ２と同一の基である。In the formula, R 1 and R 2 are the same groups as R 1 and R 2 in formula (1).
すなわち、例えば、本実施形態に係るカルボニル化合物として、ホルムアルデヒドを用いた場合、緩衝液としては、グリコール酸とグリコール酸の塩とを含有する緩衝液が好ましい。 That is, for example, when formaldehyde is used as the carbonyl compound according to the present embodiment, a buffer solution containing glycolic acid and a salt of glycolic acid is preferable as the buffer solution.
緩衝液のｐＨは７未満であり、シアノヒドリンの生成率が向上する観点からは、１〜６であることが好ましく、３〜５であることがより好ましい。ｐＨが高すぎると、シアノヒドリンからカルボニル化合物への逆反応が進行するようになるうえに、突発的な異常反応が起きやすくなり、シアノヒドリンの生成率が低下する傾向にある。また、ｐＨが低すぎると、反応自体は安定であるが反応速度が遅くなる。 The pH of the buffer solution is less than 7, and from the viewpoint of improving the production rate of cyanohydrin, it is preferably 1 to 6, and more preferably 3 to 5. If the pH is too high, the reverse reaction from cyanohydrin to the carbonyl compound proceeds, and sudden abnormal reactions are likely to occur, and the production rate of cyanohydrin tends to decrease. On the other hand, if the pH is too low, the reaction itself is stable but the reaction rate is slow.
カルボニル化合物と青酸との反応の反応速度は、緩衝液のｐＨを適宜変更することにより、精度良く制御することができる。そして、緩衝液のｐＨは、弱酸と弱酸の塩とのモル比を変更することによって、適宜調整することができる。例えば、弱酸としてグリコール酸、弱酸の塩としてグリコール酸ナトリウムを用いる場合、グリコール酸の酸解離定数（３．６３［２５℃］）からの推定で、グリコール酸（ＧＡ）とグリコール酸ナトリウム（ＧＡＮａ）とのモル比（ＧＡ／ＧＡＮａ）を、０．４３とすることにより、ｐＨが４である緩衝液を調製することができる。 The reaction rate of the reaction between the carbonyl compound and hydrocyanic acid can be accurately controlled by appropriately changing the pH of the buffer solution. The pH of the buffer solution can be adjusted as appropriate by changing the molar ratio of the weak acid to the salt of the weak acid. For example, when glycolic acid is used as the weak acid and sodium glycolate is used as the salt of the weak acid, glycolic acid (GA) and sodium glycolate (GANa) are estimated from the acid dissociation constant of glycolic acid (3.63 [25 ° C.]). When the molar ratio of (GA / GANa) is 0.43, a buffer solution having a pH of 4 can be prepared.
また、例えば、弱酸の酸解離定数をＫａとしたとき、ｐＨがＸである緩衝液を調製するためには、弱酸と弱酸の塩とのモル比Ｙ（弱酸のモル数／弱酸の塩のモル数）を、下記式（ｉ）で表される値にすればよい。
Ｙ＝１０（ｐＫａ−ｘ） …（ｉ）For example, when the acid dissociation constant of a weak acid is Ka, in order to prepare a buffer solution having a pH of X, the molar ratio Y of weak acid to weak acid salt (mol number of weak acid / mol of weak acid salt) The number may be a value represented by the following formula (i).
Y = 10 (pKa-x) (i)
緩衝液は、カルボニル化合物と青酸との反応開始時におけるｐＨと、反応完了時におけるｐＨとの差が、０〜１となるように調製されたものであることが好ましく、０〜０．５となるように調製されたものであることがより好ましい。ｐＨの変化幅を、上記のように抑制することによって、シアノヒドリンの生成率が一層顕著に向上する。また、より精度良く反応速度を制御することができるようになる。 The buffer is preferably prepared such that the difference between the pH at the start of the reaction of the carbonyl compound and hydrocyanic acid and the pH at the completion of the reaction is 0 to 1, It is more preferable that it is prepared as follows. By suppressing the change width of the pH as described above, the production rate of cyanohydrin is further remarkably improved. In addition, the reaction rate can be controlled with higher accuracy.
本実施形態に係る製造方法においては、弱酸及び弱酸の塩の緩衝液中の含有量を調整することによって、ｐＨの変化幅を上記の範囲内に抑制することができる。具体的には、反応に供するカルボニル化合物の総量に対して、弱酸の含有量を０．０２〜０．２４モル％、弱酸の塩の含有量を０．０４〜０．５２モル％とすることにより、ｐＨの変化幅を上記の範囲内に抑制することができる。 In the production method according to the present embodiment, by adjusting the content of the weak acid and the salt of the weak acid in the buffer solution, the pH change range can be suppressed within the above range. Specifically, the content of the weak acid is 0.02 to 0.24 mol% and the content of the salt of the weak acid is 0.04 to 0.52 mol% with respect to the total amount of the carbonyl compound subjected to the reaction. Thus, the change width of the pH can be suppressed within the above range.
本実施形態に係るシアノヒドリンの製造方法は、例えば、カルボニル化合物を含有し且つｐＨが７未満である緩衝液を、所定温度範囲に保持しつつ、該緩衝液に青酸を添加して、該緩衝液中でカルボニル化合物と青酸とを反応させることにより、実施することができる。 In the method for producing cyanohydrin according to the present embodiment, for example, a buffer solution containing a carbonyl compound and having a pH of less than 7 is maintained in a predetermined temperature range, while adding hydrocyanic acid to the buffer solution, the buffer solution It can be carried out by reacting a carbonyl compound and hydrocyanic acid in the reaction.
上記の所定温度範囲とは、シアノヒドリンの生成率が良好となる観点から、通常１０〜９０℃であり、好ましくは２０〜８０℃であり、より好ましくは３０〜６０℃である。当該温度が高すぎると、シアノヒドリンからカルボニル化合物への逆反応が進行するようになるうえに、突発的な異常反応を起こしやすくなり、シアノヒドリンの生成率が低下する傾向にある。また、温度が低すぎると、反応自体は安定であるが反応速度が遅くなる。 Said predetermined temperature range is 10-90 degreeC normally from a viewpoint from which the production | generation rate of cyanohydrin becomes favorable, Preferably it is 20-80 degreeC, More preferably, it is 30-60 degreeC. If the temperature is too high, the reverse reaction from cyanohydrin to the carbonyl compound proceeds, and sudden abnormal reactions are likely to occur, and the production rate of cyanohydrin tends to decrease. On the other hand, if the temperature is too low, the reaction itself is stable but the reaction rate is slow.
カルボニル化合物と青酸との反応は、上記のごとくカルボニル化合物を含有し且つ温度調整された緩衝液に、青酸を添加しながら行うことが好ましい。添加速度は、カルボニル化合物の総量に対して、好ましくは０．０５〜１０モル％／分であり、より好ましくは０．１〜５モル％／分である。添加速度が速すぎると急激なｐＨ変動を伴う場合があり、添加速度が遅すぎると工程時間が長くなり作業効率が低下する。緩衝液の温度は、青酸を添加している間、上記の所定温度範囲を維持するように調整されることが好ましく、青酸の添加が終了した後も反応が完結するまでの間、上記の所定温度範囲を維持するように調整されることが好ましい。 The reaction of the carbonyl compound and hydrocyanic acid is preferably carried out while adding hydrocyanic acid to the buffer solution containing the carbonyl compound and temperature-controlled as described above. The addition rate is preferably 0.05 to 10 mol% / min, more preferably 0.1 to 5 mol% / min, based on the total amount of the carbonyl compound. If the addition rate is too fast, there may be abrupt pH fluctuation, and if the addition rate is too slow, the process time becomes longer and the working efficiency decreases. The temperature of the buffer solution is preferably adjusted so as to maintain the above-mentioned predetermined temperature range during the addition of hydrocyanic acid, and after the addition of hydrocyanic acid is completed until the reaction is completed. It is preferable to adjust the temperature range.
カルボニル化合物と青酸との反応の反応時間は、通常１〜１０時間程度である。上述のとおり、緩衝液のｐＨを変化させることにより反応速度が調整されるため、反応時間は当該反応速度に併せて適宜調整することができる。 The reaction time of the reaction between the carbonyl compound and hydrocyanic acid is usually about 1 to 10 hours. As described above, since the reaction rate is adjusted by changing the pH of the buffer solution, the reaction time can be appropriately adjusted in accordance with the reaction rate.
カルボニル化合物と青酸との反応は、反応域の圧力を常圧としても、加圧下としてもよい。また、本実施形態に係る製造方法は、回分法及び連続法のいずれの方法でも好ましく実施することができる。連続法を採用する場合、反応域を２つ又はそれ以上に分割し、多段階で反応を実施することが好ましい。 In the reaction between the carbonyl compound and hydrocyanic acid, the pressure in the reaction zone may be normal pressure or under pressure. In addition, the production method according to this embodiment can be preferably carried out by either a batch method or a continuous method. When the continuous method is adopted, it is preferable to divide the reaction zone into two or more and carry out the reaction in multiple stages.
カルボニル化合物と青酸との反応が完了した後、シアノヒドリンを含有する反応溶液は、例えば硫酸などの酸を添加して、ｐＨを好ましくは２以下、より好ましくは１．５以下に調製することが好ましい。このように反応溶液のｐＨを調製することにより、シアノヒドリンからカルボニル化合物への逆反応が抑制され、反応溶液中でのシアノヒドリンの貯蔵安定性が向上する。 After the reaction between the carbonyl compound and hydrocyanic acid is completed, the reaction solution containing cyanohydrin is preferably adjusted to a pH of preferably 2 or less, more preferably 1.5 or less by adding an acid such as sulfuric acid. . By adjusting the pH of the reaction solution in this manner, the reverse reaction from cyanohydrin to the carbonyl compound is suppressed, and the storage stability of cyanohydrin in the reaction solution is improved.
そして、例えば、上記のごとくｐＨを調製した反応溶液について、減圧下で溶媒や残留青酸を除去し濃縮することにより、シアノヒドリンを得ることができる。濃縮時の温度は、５０℃以下であることが好ましい。濃縮時の温度が５０℃より高いと、シアノヒドリンが分解するおそれがある。 Then, for example, cyanohydrin can be obtained by removing the solvent and residual hydrocyanic acid under reduced pressure and concentrating the reaction solution whose pH has been adjusted as described above. The temperature during concentration is preferably 50 ° C. or lower. If the temperature during concentration is higher than 50 ° C., cyanohydrin may be decomposed.
以上、本発明の好適な実施形態について説明したが、本発明は上記実施形態に限定されるものではない。 The preferred embodiment of the present invention has been described above, but the present invention is not limited to the above embodiment.
次に、実施例を挙げて本発明をさらに詳細に説明する。但し、本発明は下記の実施例に限定されるものではなく、本発明の要旨を変更しない範囲において適宜変更して実施できるものである。 Next, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples, and can be appropriately modified and implemented without departing from the scope of the present invention.
（実施例１）
反応器に、３７質量％ホルムアルデヒド水溶液７９．５４質量部、グリコール酸（純度９７質量％）０．１７質量部、グリコール酸ナトリウム（純度９７質量％）０．５０質量部、及び水６０質量部を量り取り、撹拌、溶解しながら４５℃に昇温した。この混合溶液の４５℃におけるｐＨは３．９であった。Example 1
In the reactor, 79.54 parts by mass of a 37% by mass aqueous formaldehyde solution, 0.17 parts by mass of glycolic acid (purity 97% by mass), 0.50 parts by mass of sodium glycolate (purity 97% by mass), and 60 parts by mass of water were added. The temperature was raised to 45 ° C. while weighing, stirring and dissolving. The pH of this mixed solution at 45 ° C. was 3.9.
この混合溶液中に、液体青酸２７．８１質量部を３０分間かけて滴下した。液体青酸を全量滴下した直後の反応液のｐＨは４．１であった。その後、４５℃にてさらに１時間撹拌した。反応完結時の反応液のｐＨは４．１であり、グリコロニトリル生成率は９６％（ホルムアルデヒド基準）であった。 In this mixed solution, 27.81 parts by mass of liquid hydrocyanic acid was added dropwise over 30 minutes. The pH of the reaction solution immediately after dropping all of the liquid hydrocyanic acid was 4.1. Then, it stirred at 45 degreeC for further 1 hour. The pH of the reaction solution at the completion of the reaction was 4.1, and the glycolonitrile production rate was 96% (formaldehyde basis).
（実施例２）
反応器に、３７質量％ホルムアルデヒド水溶液７９．５４質量部、グリコール酸（純度９７質量％）０．０２質量部、グリコール酸ナトリウム（純度９７質量％）０．０５質量部、及び水６０質量部を量り取り、撹拌、溶解しながら４５℃に昇温した。この混合溶液の４５℃におけるｐＨは３．６であった。(Example 2)
In a reactor, 79.54 parts by mass of a 37% by mass aqueous formaldehyde solution, 0.02 parts by mass of glycolic acid (purity 97% by mass), 0.05 parts by mass of sodium glycolate (purity 97% by mass), and 60 parts by mass of water were added. The temperature was raised to 45 ° C. while weighing, stirring and dissolving. The pH of this mixed solution at 45 ° C. was 3.6.
この混合溶液中に、液体青酸２７．８１質量部を３０分間かけて滴下した。液体青酸を全量滴下した直後の反応液のｐＨは３．７であった。その後、４５℃にてさらに１．５時間攪拌した。反応完結時の反応液のｐＨは３．８であり、グリコロニトリル生成率は９６％（ホルムアルデヒド基準）であった。 In this mixed solution, 27.81 parts by mass of liquid hydrocyanic acid was added dropwise over 30 minutes. The pH of the reaction solution immediately after dropping all of the liquid hydrocyanic acid was 3.7. Thereafter, the mixture was further stirred at 45 ° C. for 1.5 hours. The pH of the reaction solution at the completion of the reaction was 3.8, and the glycolonitrile production rate was 96% (formaldehyde standard).
（実施例３）
反応器に、３７質量％ホルムアルデヒド水溶液７９．５４質量部、グリコール酸（純度９７質量％）０．３３質量部、グリコール酸ナトリウム（純度９７質量％）０．９９質量部、及び水６０質量部を量り取り、撹拌、溶解しながら４５℃に昇温した。この混合溶液の４５℃におけるｐＨは４．０であった。(Example 3)
In the reactor, 79.54 parts by mass of a 37% by mass aqueous formaldehyde solution, 0.33 parts by mass of glycolic acid (purity 97% by mass), 0.99 parts by mass of sodium glycolate (purity 97% by mass), and 60 parts by mass of water were added. The temperature was raised to 45 ° C. while weighing, stirring and dissolving. The pH of this mixed solution at 45 ° C. was 4.0.
この混合溶液中に、液体青酸２７．８１質量部を３０分間かけて滴下した。液体青酸を全量滴下した直後の反応液のｐＨは４．２であった。その後、４５℃にてさらに１時間攪拌した。反応完結時の反応液のｐＨは４．２であり、グリコロニトリル生成率は９７％（ホルムアルデヒド基準）であった。 In this mixed solution, 27.81 parts by mass of liquid hydrocyanic acid was added dropwise over 30 minutes. The pH of the reaction solution immediately after dropping all of the liquid hydrocyanic acid was 4.2. Then, it stirred at 45 degreeC for further 1 hour. When the reaction was completed, the pH of the reaction solution was 4.2, and the glycolonitrile production rate was 97% (formaldehyde standard).
（実施例４）
反応器に、アセトアルデヒド５７．３２質量部、乳酸（純度９０質量％）０．３０質量部、乳酸ナトリウム（純度９０質量％）０．８１質量部、及び水２４．０５質量部を量り取り、撹拌、溶解し、７℃に冷却した。この混合溶液の７℃におけるｐＨは５．３であった。Example 4
In a reactor, 57.32 parts by mass of acetaldehyde, 0.30 parts by mass of lactic acid (purity 90% by mass), 0.81 parts by mass of sodium lactate (purity 90% by mass), and 24.05 parts by mass of water are weighed and stirred. , Dissolved and cooled to 7 ° C. The pH of this mixed solution at 7 ° C. was 5.3.
この混合溶液中に、液体青酸３６．９０質量部を１時間かけて滴下した。液体青酸を全量滴下した直後の反応液のｐＨは４．５であった。その後、２０℃に昇温してさらに２時間攪拌した。反応完結時の反応液のｐＨは４．３であり、ラクトニトリル生成率は９９％（アセトアルデヒド基準）であった。 In this mixed solution, 36.90 mass parts of liquid hydrocyanic acid was dripped over 1 hour. The pH of the reaction solution immediately after dropping all of the liquid hydrocyanic acid was 4.5. Then, it heated up at 20 degreeC and stirred for further 2 hours. The pH of the reaction liquid at the completion of the reaction was 4.3, and the lactonitrile production rate was 99% (based on acetaldehyde).
（比較例１）
反応器に、３７質量％ホルムアルデヒド水溶液７９．５４質量部及び水６０質量部を量り取り、撹拌しながら４５℃に昇温した。この溶液の４５℃におけるｐＨは４．４であった。(Comparative Example 1)
In the reactor, 79.54 parts by mass of 37% by mass aqueous formaldehyde solution and 60 parts by mass of water were weighed and heated to 45 ° C. while stirring. The pH of this solution at 45 ° C. was 4.4.
この溶液中に、０．５質量％硫酸水溶液０．０６質量部及び０．１質量％苛性ソーダ水溶液０．１３質量部を添加して、ｐＨを４．１とした。この液中に、液体青酸２７．０３質量部を３０分間かけて滴下したところ、反応液のｐＨは徐々に低下し、液体青酸を全量滴下した直後の反応液のｐＨは２．７となった。その後、４５℃にてさらに１時間撹拌した。１時間撹拌後の反応液のｐＨは２．７であり、グリコロニトリル生成率は８６％（ホルムアルデヒド基準）であった。 To this solution, 0.06 part by mass of a 0.5% by mass sulfuric acid aqueous solution and 0.13 part by mass of a 0.1% by mass caustic soda aqueous solution were added to adjust the pH to 4.1. When 27.03 parts by mass of liquid hydrocyanic acid was added dropwise to this solution over 30 minutes, the pH of the reaction solution gradually decreased, and the pH of the reaction solution immediately after adding all of the liquid hydrocyanic acid was 2.7. . Then, it stirred at 45 degreeC for further 1 hour. The pH of the reaction solution after stirring for 1 hour was 2.7, and the glycolonitrile production rate was 86% (formaldehyde reference).
以上の結果から、酸と塩基で単純にｐＨを調整しただけの液中で、カルボニル化合物と青酸とを反応させると、反応進行に伴ってｐＨが変動して、シアノヒドリンの生成率があまり高くならないことがわかる。これに対して、酸性側のｐＨに調整された緩衝液中で、カルボニル化合物と青酸とを反応させると、ｐＨが大きく変動しないため反応速度が適切な範囲で安定し、シアノヒドリンの生成率が高くなることがわかる。 From the above results, when a carbonyl compound and hydrocyanic acid are reacted in a solution in which the pH is simply adjusted with an acid and a base, the pH fluctuates with the progress of the reaction, and the production rate of cyanohydrin does not increase so much. I understand that. In contrast, when a carbonyl compound and hydrocyanic acid are reacted in a buffer adjusted to an acidic pH, the pH does not fluctuate greatly, so the reaction rate is stabilized within an appropriate range, and the rate of cyanohydrin production is high. I understand that
Claims (8)
前記カルボニル化合物と前記青酸との反応は、触媒の非存在下、又はシアン化ナトリウム及びシアン化カリウムからなる群より選択される触媒の存在下で行われる、シアノヒドリンの製造方法。 While holding a buffer solution containing a carbonyl compound and having a pH of less than 7 at 10 to 90 ° C. , hydrocyanic acid is added to the buffer solution, and the carbonyl compound and the hydrocyanic acid are reacted in the buffer solution. And obtaining a cyanohydrin
The method for producing cyanohydrin, wherein the reaction of the carbonyl compound and the hydrocyanic acid is carried out in the absence of a catalyst or in the presence of a catalyst selected from the group consisting of sodium cyanide and potassium cyanide.
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| CN106631889B (en) * | 2016-12-16 | 2018-08-21 | 阳泉煤业（集团）有限责任公司 | A kind of process for separation and purification of hydroxyacetonitrile |
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