JP2016210717A - Production process for n-acylamino acid - Google Patents
Production process for n-acylamino acid Download PDFInfo
- Publication number
- JP2016210717A JP2016210717A JP2015094823A JP2015094823A JP2016210717A JP 2016210717 A JP2016210717 A JP 2016210717A JP 2015094823 A JP2015094823 A JP 2015094823A JP 2015094823 A JP2015094823 A JP 2015094823A JP 2016210717 A JP2016210717 A JP 2016210717A
- Authority
- JP
- Japan
- Prior art keywords
- mass
- minutes
- solution
- reaction
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002253 acid Substances 0.000 title claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000003960 organic solvent Substances 0.000 claims abstract description 25
- 150000001413 amino acids Chemical class 0.000 claims abstract description 24
- 238000005917 acylation reaction Methods 0.000 claims abstract description 23
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 22
- 239000000194 fatty acid Substances 0.000 claims abstract description 22
- 229930195729 fatty acid Natural products 0.000 claims abstract description 22
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 22
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000012046 mixed solvent Substances 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 238000005192 partition Methods 0.000 claims abstract description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 6
- 150000001340 alkali metals Chemical group 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000003513 alkali Substances 0.000 abstract description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 75
- 239000012074 organic phase Substances 0.000 description 43
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 31
- 239000000203 mixture Substances 0.000 description 26
- 238000000034 method Methods 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 20
- 239000008346 aqueous phase Substances 0.000 description 18
- 230000010933 acylation Effects 0.000 description 16
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 235000021588 free fatty acids Nutrition 0.000 description 12
- 238000004821 distillation Methods 0.000 description 11
- MLQBTMWHIOYKKC-KTKRTIGZSA-N (z)-octadec-9-enoyl chloride Chemical compound CCCCCCCC\C=C/CCCCCCCC(Cl)=O MLQBTMWHIOYKKC-KTKRTIGZSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- DIOYAVUHUXAUPX-ZHACJKMWSA-N 2-[methyl-[(e)-octadec-9-enoyl]amino]acetic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)N(C)CC(O)=O DIOYAVUHUXAUPX-ZHACJKMWSA-N 0.000 description 8
- 108010077895 Sarcosine Proteins 0.000 description 8
- 229940043230 sarcosine Drugs 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- JNKSXSJNLXMTSV-KTKRTIGZSA-N (z)-docos-13-enoyl chloride Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(Cl)=O JNKSXSJNLXMTSV-KTKRTIGZSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- WUOACPNHFRMFPN-UHFFFAOYSA-N alpha-terpineol Chemical compound CC1=CCC(C(C)(C)O)CC1 WUOACPNHFRMFPN-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- SQIFACVGCPWBQZ-UHFFFAOYSA-N delta-terpineol Natural products CC(C)(O)C1CCC(=C)CC1 SQIFACVGCPWBQZ-UHFFFAOYSA-N 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 229940116411 terpineol Drugs 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940000635 beta-alanine Drugs 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000013076 target substance Substances 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- FBWMYSQUTZRHAT-HZJYTTRNSA-N (9z,12z)-octadeca-9,12-dienoyl chloride Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(Cl)=O FBWMYSQUTZRHAT-HZJYTTRNSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZONJATNKKGGVSU-UHFFFAOYSA-N 14-methylpentadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCC(O)=O ZONJATNKKGGVSU-UHFFFAOYSA-N 0.000 description 1
- LFDKQJVNMJFNGG-UHFFFAOYSA-N 16-methylheptadecanoyl chloride Chemical compound CC(C)CCCCCCCCCCCCCCC(Cl)=O LFDKQJVNMJFNGG-UHFFFAOYSA-N 0.000 description 1
- LFJJOPDNPVFCNZ-UHFFFAOYSA-N 2-[hexadecanoyl(methyl)amino]acetic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N(C)CC(O)=O LFJJOPDNPVFCNZ-UHFFFAOYSA-N 0.000 description 1
- FSGABGHJNIKWIW-UHFFFAOYSA-N 3-(methylamino)propanoic acid;sodium Chemical compound [Na].CNCCC(O)=O FSGABGHJNIKWIW-UHFFFAOYSA-N 0.000 description 1
- ZRNBEAAEJJLWTJ-KHPPLWFESA-N 3-[methyl-[(z)-octadec-9-enoyl]amino]propanoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)N(C)CCC(O)=O ZRNBEAAEJJLWTJ-KHPPLWFESA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- VDIPNVCWMXZNFY-UHFFFAOYSA-N N-methyl-beta-alanine Chemical compound CNCCC(O)=O VDIPNVCWMXZNFY-UHFFFAOYSA-N 0.000 description 1
- 238000003436 Schotten-Baumann reaction Methods 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- QTHQYNCAWSGBCE-UHFFFAOYSA-N docosanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCCCCCC(Cl)=O QTHQYNCAWSGBCE-UHFFFAOYSA-N 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- WTBAHSZERDXKKZ-UHFFFAOYSA-N octadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCC(Cl)=O WTBAHSZERDXKKZ-UHFFFAOYSA-N 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 238000006227 trimethylsilylation reaction Methods 0.000 description 1
- -1 unsaturated fatty acid chlorides Chemical class 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
本発明はN−アシルアミノ酸の製造方法に関する。 The present invention relates to a method for producing an N-acylamino acid.
N−アシルアミノ酸を製造する方法としては、アミノ酸と脂肪酸クロリドとをアルカリ条件下にてショッテンバウマン反応により反応させた後、酸を用いてN−アシルアミノ酸として単離する方法が一般に知られている。
アシルアミノ酸の製造については、溶媒として水のみを用いても反応が進行することが知られているが、アシル基が長鎖の場合には水を溶媒として反応させると生成物や塩の生成により反応溶液が増粘するので、特に高濃度で反応を行う場合は攪拌が不十分となり、副反応である脂肪酸の生成反応が起こりやすくなる。
一方、粘度上昇を抑制するために溶媒である水の量を増やし、低濃度で反応させた場合も、副反応である脂肪酸の生成が促進されてしまう。
そのため、N−アシルアミノ酸の純度を上げる様々な試みがなされてきた。
As a method for producing an N-acylamino acid, a method in which an amino acid and a fatty acid chloride are reacted by a Schotten-Baumann reaction under an alkaline condition and then isolated as an N-acylamino acid using an acid is generally known. Yes.
For the production of acylamino acids, it is known that the reaction proceeds even when only water is used as a solvent. However, when the acyl group is a long chain, reaction with water as a solvent causes formation of products and salts. Since the reaction solution is thickened, stirring is insufficient particularly when the reaction is performed at a high concentration, and a fatty acid production reaction as a side reaction is likely to occur.
On the other hand, even when the amount of water as a solvent is increased in order to suppress an increase in viscosity and the reaction is carried out at a low concentration, the production of fatty acid as a side reaction is promoted.
For this reason, various attempts have been made to increase the purity of N-acylamino acids.
例えば、特許文献1には、β−アラニンと長鎖脂肪酸クロリドを水酸化カリウム存在下で水を溶媒として反応させる方法が開示されている。本方法では、生成物の水への溶解性を上げるために水酸化カリウムを用いており、さらに反応温度を60〜90℃と高く設定することで粘度上昇を抑制している。しかしながら、本方法では反応温度が高いので得られる生成物の色相が悪化してしまうことがある。洗浄剤などの用途においては、アシルアミノ酸の色相が製品の色相に影響することがあるので、良好な色相が望まれる。 For example, Patent Document 1 discloses a method in which β-alanine and a long-chain fatty acid chloride are reacted with water as a solvent in the presence of potassium hydroxide. In this method, potassium hydroxide is used to increase the solubility of the product in water, and the increase in viscosity is suppressed by setting the reaction temperature as high as 60 to 90 ° C. However, since the reaction temperature is high in this method, the hue of the resulting product may be deteriorated. In applications such as cleaning agents, the hue of the acylamino acid may affect the hue of the product, so a good hue is desired.
また、反応溶媒として水と親水性有機溶媒との均一混合溶媒を用いることで反応溶液の粘度上昇を抑制することが試みられている。例えば、特許文献2には、酸性アミノ酸と長鎖脂肪酸クロライドをアルカリの存在下に縮合させる際に、反応溶媒としてアセトン、メチルエチルケトン、ジオキサン、テトラヒドロフランなどの親水性有機溶媒と水との混合溶媒を用いることで、N−長鎖アシル酸性アミノ酸が高収率で得られることが開示されている。
また、特許文献3には、中性アミノ酸と脂肪酸クロライドとを、親水性有機溶媒と水との混合物中で塩基の存在下で反応させて、N−長鎖アシル中性アミノ酸の純度を高める方法が開示されている。
しかしながら、これらの方法では親水性溶媒を用いるので、精製工程において水層へ生成物の一部が溶解して、収率が低下することがある。さらに水層へ生成物の一部が溶解することで、水と親水性有機溶媒混合液と生成物の乳化層が生じることがあるので、乳化層を分離することで収率が低下することがある。また、乳化を解除するために加温すると、収率低下は抑制されるが、色相が悪化することがある。
In addition, attempts have been made to suppress an increase in the viscosity of the reaction solution by using a homogeneous mixed solvent of water and a hydrophilic organic solvent as the reaction solvent. For example, in Patent Document 2, when an acidic amino acid and a long-chain fatty acid chloride are condensed in the presence of an alkali, a mixed solvent of water and a hydrophilic organic solvent such as acetone, methyl ethyl ketone, dioxane, and tetrahydrofuran is used as a reaction solvent. Thus, it is disclosed that an N-long chain acyl acidic amino acid can be obtained in high yield.
Patent Document 3 discloses a method for increasing the purity of an N-long chain acyl neutral amino acid by reacting a neutral amino acid and a fatty acid chloride in a mixture of a hydrophilic organic solvent and water in the presence of a base. Is disclosed.
However, since a hydrophilic solvent is used in these methods, a part of the product may be dissolved in the aqueous layer in the purification process, and the yield may be reduced. Furthermore, since a part of the product is dissolved in the aqueous layer, an emulsion layer of water, a hydrophilic organic solvent mixture and the product may be formed, and thus the yield may be reduced by separating the emulsion layer. is there. Moreover, when it heats in order to cancel | release emulsification, a yield fall will be suppressed, but a hue may deteriorate.
このように、良好な色相を有する高純度なN−アシルアミノ酸を高収率で得ることは従来技術では困難であり、色相、純度の良好なN−アシルアミノ酸を高収率で得ることができる新たな方法が求められていた。 Thus, it is difficult to obtain a high-purity N-acylamino acid having a good hue in a high yield by the conventional technique, and a N-acylamino acid having a good hue and purity can be obtained in a high yield. A new method was sought.
本発明は、良好な色相を有する高純度なN−アシルアミノ酸を高収率で得られる製造方法を提供することを目的とする。 An object of this invention is to provide the manufacturing method which can obtain the highly purified N-acylamino acid which has a favorable hue with a high yield.
本発明者らは、上記課題を解決するために鋭意検討を行った結果、特定のアミノ酸と特定の脂肪酸クロリドとをアルカリ条件下にてアシル化反応させるに際して、所定のオクタノール/水分配係数を有する有機溶媒と水との混合溶媒中で反応を行なうことによって、上記課題を解決できることを見出し、本発明を完成させるに至った。 As a result of intensive studies to solve the above problems, the present inventors have a predetermined octanol / water partition coefficient when acylating a specific amino acid and a specific fatty acid chloride under alkaline conditions. It has been found that the above problem can be solved by carrying out the reaction in a mixed solvent of an organic solvent and water, and the present invention has been completed.
すなわち、本発明は、式(1)で表されるアミノ酸と炭素数16〜22の脂肪酸クロリドとを、オクタノール/水分配係数が1.6〜3.5である有機溶媒と水との混合溶媒中、アルカリ条件下にてアシル化反応させることを特徴とするN−アシルアミノ酸の製造方法である。
本発明の製造方法によれば、式(1)で表されるアミノ酸と炭素数16〜22の脂肪酸クロリドとから、良好な色相を有する高純度なN−アシルアミノ酸を高収率で製造することができる。 According to the production method of the present invention, a highly pure N-acylamino acid having a good hue is produced in high yield from the amino acid represented by the formula (1) and a fatty acid chloride having 16 to 22 carbon atoms. Can do.
以下、本発明の実施形態について説明する。
本発明の製造方法は、特定のアミノ酸と特定の脂肪酸クロリドとを、オクタノール/水分配係数が1.6〜3.5である有機溶媒と水との混合溶媒中、アルカリ条件下にてアシル化反応させることを特徴とし、後記のアシル化工程を少なくとも有するものである。また、通常は、アシル化工程の後に、分層工程、水洗工程および溶媒留去工程を経ることによって、目的のN−アシルアミノ酸が製造される。
Hereinafter, embodiments of the present invention will be described.
In the production method of the present invention, a specific amino acid and a specific fatty acid chloride are acylated in a mixed solvent of an organic solvent and water having an octanol / water partition coefficient of 1.6 to 3.5 under alkaline conditions. The reaction is characterized by having at least an acylation step described later. Further, usually, the target N-acylamino acid is produced through a separation step, a water washing step and a solvent distillation step after the acylation step.
本発明で用いられるアミノ酸は式(1)で表されるアミノ酸である。式中、R1は水素原子またはメチル基を示し、好ましくはメチル基である。R2は水素原子またはアルカリ金属原子を示し、アルカリ金属としては、例えば、リチウム、ナトリウム、カリウムなどが挙げられ、好ましくはナトリウムやカリウムである。nは1または2の整数を示す。式(1)で表されるアミノ酸としては、具体的には、グリシン、N−メチルグリシン(以下、ザルコシンともいう。)、β−アラニン、N−メチル−β−アラニンが挙げられる。 The amino acid used in the present invention is an amino acid represented by the formula (1). In the formula, R 1 represents a hydrogen atom or a methyl group, preferably a methyl group. R 2 represents a hydrogen atom or an alkali metal atom. Examples of the alkali metal include lithium, sodium, potassium, and the like, preferably sodium or potassium. n represents an integer of 1 or 2. Specific examples of the amino acid represented by the formula (1) include glycine, N-methylglycine (hereinafter also referred to as sarcosine), β-alanine, and N-methyl-β-alanine.
式(1)で表されるアミノ酸と反応させる脂肪酸クロリドは、炭素数16〜22の飽和または不飽和脂肪酸の塩化物である。脂肪酸の炭素鎖は直鎖状、分岐状、またはそれらの組み合わせのいずれでもよく、1個以上の不飽和結合を含んでいてもよい。かかる脂肪酸クロリドとしては、例えば、パルミチン酸クロリド、イソパルミチン酸クロリド、ステアリン酸クロリド、イソステアリン酸クロリド、オレイン酸クロリド、リノール酸クロリド、リノレン酸クロリド、ベヘニン酸クロリド、エルカ酸クロリドなどが挙げられる。好ましくはオレイン酸クロリド、エルカ酸クロリドなどの不飽和脂肪酸クロリドである。 The fatty acid chloride to be reacted with the amino acid represented by the formula (1) is a chloride of a saturated or unsaturated fatty acid having 16 to 22 carbon atoms. The carbon chain of the fatty acid may be linear, branched, or a combination thereof, and may contain one or more unsaturated bonds. Examples of the fatty acid chloride include palmitic acid chloride, isopalmitic acid chloride, stearic acid chloride, isostearic acid chloride, oleic acid chloride, linoleic acid chloride, linolenic acid chloride, behenic acid chloride, erucic acid chloride, and the like. Preferred are unsaturated fatty acid chlorides such as oleic acid chloride and erucic acid chloride.
本発明で用いられる有機溶媒は、所定のオクタノール/水分配係数(Pow)を有する。オクタノール/水分配係数(Pow)とは、二つの混じり合わない溶媒からなる二相へ溶解した物質の平衡濃度の比であり、本発明においては日本工業規格(JIS Z 7260‐107 (2000))の分配係数(1-オクタノール/水)の測定−フラスコ振とう法により測定される値である。
本発明において水と混合して反応に使用される有機溶媒はPowが1.6〜3.5である。Powが小さすぎる有機溶媒を用いると、水相と混和してしまい、乳化層ができるので収率の低下を招くことがあり、また分層させるために高温にしなければならず、アシル化物の分解による純度低下や色相の悪化が起こることがある。Powが大きすぎる有機溶媒を用いると、副反応である脂肪酸の生成反応が起こり易くなることにより純度の低下を招いたり、油水分離の際に未反応のアミノ酸が水相へ溶解することにより収率の低下を招くことがある。
Powが1.6〜3.5である有機溶媒としては、例えば、クロロホルム(Pow=1.97)、ベンゼン(Pow=2.13)、イソプレン(Pow=2.42)、トルエン(Pow=2.69)、クロロベンゼン(Pow=2.89)、テルピネオール(Pow=2.98)、エチルベンゼン(Pow=3.15)、シクロヘキサン(Pow=3.44)等が挙げられる。Powの好ましい範囲は2.0〜3.3であり、さらに好ましい範囲は2.4〜3.2であり、特に好ましい範囲は2.6〜3.0である。好ましい有機溶媒としては、例えば、トルエン、テルピネオールが挙げられ、より好ましくはトルエンが挙げられる。
The organic solvent used in the present invention has a predetermined octanol / water partition coefficient (P ow ). The octanol / water partition coefficient (P ow ) is a ratio of equilibrium concentrations of substances dissolved in two phases composed of two immiscible solvents. In the present invention, Japanese Industrial Standard (JIS Z 7260-107 (2000) ) Distribution coefficient (1-octanol / water)-a value measured by a flask shaking method.
In the present invention, the organic solvent used for the reaction by mixing with water has a P ow of 1.6 to 3.5. If an organic solvent having an excessively small Pow is used, it will be miscible with the aqueous phase and an emulsion layer will be formed, which may lead to a decrease in yield. Degradation of purity and deterioration of hue may occur due to decomposition. If an organic solvent having an excessively large Pow is used, the generation reaction of fatty acid, which is a side reaction, easily occurs, resulting in a decrease in purity, or the unreacted amino acid dissolves in the aqueous phase during oil-water separation. The rate may be reduced.
Examples of the organic solvent having P ow of 1.6 to 3.5 include chloroform (P ow = 1.97), benzene (P ow = 2.13), isoprene (P ow = 2.42), toluene ( Pow = 2.69), chlorobenzene ( Pow = 2.89), terpineol ( Pow = 2.98), ethylbenzene ( Pow = 3.15), cyclohexane ( Pow = 3.44), etc. Can be mentioned. A preferred range of P ow is 2.0 to 3.3, more preferred range is 2.4 to 3.2, particularly preferred range is 2.6 to 3.0. Preferable organic solvents include, for example, toluene and terpineol, more preferably toluene.
アシル化反応における混合溶媒中の水の量は、反応に供される式(1)のアミノ酸1質量部に対して、好ましくは2〜10質量部、さらに好ましくは4〜8質量部である。
また、アシル化反応における混合溶媒中の有機溶媒の量は、反応に用いる水に対する質量比(有機溶媒/水)にて、好ましくは0.05〜1、さらに好ましくは0.1〜0.25である。
The amount of water in the mixed solvent in the acylation reaction is preferably 2 to 10 parts by mass, more preferably 4 to 8 parts by mass with respect to 1 part by mass of the amino acid of formula (1) to be subjected to the reaction.
Further, the amount of the organic solvent in the mixed solvent in the acylation reaction is preferably 0.05 to 1, more preferably 0.1 to 0.25 in terms of a mass ratio (organic solvent / water) to water used in the reaction. It is.
(アシル化工程)
本発明においてアシル化反応はアルカリ条件下、好ましくはpH10〜14の反応液中で行なう。反応液をアルカリ条件にする方法として、例えば、アルカリ化合物を反応溶液に存在させる方法が挙げられる。例えば、式(1)で表されるアミノ酸を水、有機溶媒およびアルカリ化合物の存在下で溶解し、その反応液に脂肪酸クロリドを滴下する。
使用するアルカリ化合物としては、例えば、水酸化ナトリウム、水酸化カリウム、炭酸ナトリウム、アンモニアなどが挙げられる。
本発明においてアシル化反応の反応温度は特に限定されないが、反応の進行と目的物質の色相の観点から、好ましくは0〜50℃、さらに好ましくは10〜40℃の範囲である。
式(1)で表されるアミノ酸と脂肪酸クロリドとの使用割合については、目的物質を高収率で得るために、前者を後者に対して同モル以上用いるのが好ましい。すなわち、脂肪酸クロリドに対する式(1)のアミノ酸の使用割合(アミノ酸/脂肪酸クロリドのモル比)が1.0〜1.5の範囲が好ましい。
(Acylation step)
In the present invention, the acylation reaction is carried out under alkaline conditions, preferably in a reaction solution having a pH of 10 to 14. Examples of the method for bringing the reaction solution into an alkaline condition include a method in which an alkali compound is present in the reaction solution. For example, the amino acid represented by the formula (1) is dissolved in the presence of water, an organic solvent and an alkali compound, and fatty acid chloride is dropped into the reaction solution.
Examples of the alkali compound to be used include sodium hydroxide, potassium hydroxide, sodium carbonate, ammonia and the like.
In the present invention, the reaction temperature of the acylation reaction is not particularly limited, but is preferably in the range of 0 to 50 ° C., more preferably 10 to 40 ° C., from the viewpoint of the progress of the reaction and the hue of the target substance.
Regarding the use ratio of the amino acid represented by the formula (1) and the fatty acid chloride, the former is preferably used in the same mole or more with respect to the latter in order to obtain the target substance in high yield. That is, the use ratio (amino acid / fatty acid chloride molar ratio) of the amino acid of the formula (1) to the fatty acid chloride is preferably in the range of 1.0 to 1.5.
反応を行う際は反応率を上げるために、式(1)で表されるアミノ酸を水および有機溶媒に溶解した後、攪拌下で脂肪酸クロリドを徐々に滴下する方法が好ましい。反応時間は各種条件によって異なるが、脂肪酸クロリドの滴下時間は通常30分間から6時間程度であり、滴下後の反応時間は通常10分間から4時間程度である。 In carrying out the reaction, a method in which the amino acid represented by the formula (1) is dissolved in water and an organic solvent and then the fatty acid chloride is gradually added dropwise with stirring in order to increase the reaction rate. Although the reaction time varies depending on various conditions, the dropping time of fatty acid chloride is usually about 30 minutes to 6 hours, and the reaction time after dropping is usually about 10 minutes to 4 hours.
(分層工程)
反応終了後、反応混合物を硫酸、塩酸などの鉱酸で酸性に調整し、温度を60〜80℃程度まで上昇させる。その後、攪拌を停止し、10分間から1時間程度その温度を維持したまま静置させて有機相と水相に分層し、これから有機相を分離する。
(Layer separation process)
After completion of the reaction, the reaction mixture is acidified with a mineral acid such as sulfuric acid and hydrochloric acid, and the temperature is raised to about 60 to 80 ° C. Thereafter, the stirring is stopped, and the mixture is allowed to stand while maintaining the temperature for about 10 minutes to 1 hour to separate into an organic phase and an aqueous phase, and the organic phase is separated therefrom.
(水洗工程)
分離した有機相に5〜10質量%の硫酸、塩酸、クエン酸などの酸性水溶液を、有機相の質量に対し、70〜90質量%加え、攪拌下で温度を60〜80℃程度まで上昇させる。その後、攪拌を停止し、通常10分間から1時間程度その温度を維持したまま静置させて有機相と水相に分層する。残存するアルカリ金属を低減させるために、分離した有機相に対し同様の操作を複数回行ってもよい。
(Washing process)
To the separated organic phase, 5 to 10% by mass of an acidic aqueous solution such as sulfuric acid, hydrochloric acid or citric acid is added to 70 to 90% by mass with respect to the mass of the organic phase, and the temperature is raised to about 60 to 80 ° C. with stirring. . Thereafter, the stirring is stopped, and the mixture is allowed to stand while maintaining the temperature for about 10 minutes to 1 hour, and is separated into an organic phase and an aqueous phase. In order to reduce the remaining alkali metal, the same operation may be performed a plurality of times on the separated organic phase.
(溶媒留去工程)
分離取得した有機相から水および有機溶媒を留去するために、通常、40〜100℃に加熱して蒸留を行う。必要に応じて減圧を行って蒸留を行うことができる。
(Solvent distillation step)
In order to distill off water and the organic solvent from the separated organic phase, the distillation is usually performed by heating to 40 to 100 ° C. If necessary, distillation can be performed under reduced pressure.
〔実施例1〜5および比較例1〜4〕
以下、実施例および比較例によりさらに具体的に説明する。また、実施例および比較例で得られたN−アシルアミノ酸について下記のとおり分析を行った。
[Examples 1 to 5 and Comparative Examples 1 to 4]
Hereinafter, it demonstrates further more concretely by an Example and a comparative example. In addition, the N-acylamino acids obtained in Examples and Comparative Examples were analyzed as follows.
(1)収率
収率は、反応に使用した脂肪酸クロリドに対するN−アシルアミノ酸の理論量である。
(1) Yield Yield is the theoretical amount of N-acylamino acid relative to the fatty acid chloride used in the reaction.
(2)遊離脂肪酸含有量
含有される遊離脂肪酸の定量は、ガスクロマトグラフィー(島津製作所(株)製、GC-2014)にてFID検出器を用いて下記表1に記載の条件で測定を行った。カラムはOV−1(パックドカラム)を使用した。
(2) Free fatty acid content The amount of free fatty acid contained was measured by gas chromatography (Shimadzu Corporation, GC-2014) using an FID detector under the conditions shown in Table 1 below. It was. The column used was OV-1 (packed column).
測定サンプルは1,1,1,3,3,3-ヘキサメチルジシラザンおよびトリメチルクロロシランを使用してトリメチルシリル化して作製し、測定を行った。 A measurement sample was prepared by trimethylsilylation using 1,1,1,3,3,3-hexamethyldisilazane and trimethylchlorosilane, and measurement was performed.
(3)純度
純度は100質量%から遊離脂肪酸含有量を引いた値とした。
(3) Purity Purity was a value obtained by subtracting the free fatty acid content from 100% by mass.
(4)色相
色相はJOCS(日本油化学会制定、基準油脂分析試験法)2.2.1.3のガードナー法に従って測定を行った。なお、数値が小さければ小さいほど好ましく、ガードナーで4以下が好ましく、3以下がさらに好ましい。
(4) Hue Hue was measured according to the Gardner method of JOCS (Established by the Japan Oil Chemists' Society, Standard Oil Analysis Test) 2.2.1.3. In addition, it is so preferable that a numerical value is small, 4 or less are preferable with a Gardner, and 3 or less are more preferable.
〔実施例1〕
(アシル化工程)
40質量%のザルコシンナトリウム水溶液138.7g(0.50mol)、水167.7g、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)、トルエン(Pow=2.69)33.6gの混合溶液に冷却しながらオレイン酸クロリド72.1g(0.24mol)を30分間かけて滴下した。その後、30℃で15分間反応させ、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)を加え、冷却しながらオレイン酸クロリド72.1g(0.24mol)を30分間かけて滴下し、その後30℃で15分間反応させた。本アシル化工程における反応液のpHは11〜14であった。
[Example 1]
(Acylation step)
138.7 g (0.50 mol) of 40% by weight aqueous sarcosine sodium solution, 167.7 g of water, 57.9 g of 24% by weight aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), toluene (P ow = 2.69) ) 72.1 g (0.24 mol) of oleic acid chloride was added dropwise over 30 minutes while cooling to 33.6 g of the mixed solution. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) was added, and 72.1 g (0.24 mol) of oleic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.
(分層工程)
62. 5質量%の硫酸水溶液を滴下して溶液のpHを2にし、また溶液の温度を70℃に調整した。滴下終了後、攪拌を停止し、30分間70℃で静置すると、有機相と水相とに分層し、これから有機相を分離した。
(Layer separation process)
62. A 5% by mass sulfuric acid aqueous solution was added dropwise to bring the pH of the solution to 2, and the temperature of the solution was adjusted to 70 ° C. After completion of the dropwise addition, the stirring was stopped and the mixture was allowed to stand at 70 ° C. for 30 minutes.
(水洗工程)
分離した有機相に5.5質量%のクエン酸水溶液180.3gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置すると、有機相と水相とに分層した。分離した有機相に5.5質量%のクエン酸水溶液180.3gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置させて有機相と水相とに分層した後、有機相を分離した。
(Washing process)
To the separated organic phase, 180.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase, 180.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.
(溶媒留去工程)
分離取得した有機相を圧力30mmHgの下、60℃で減圧蒸留を行った。
得られたN−オレオイルザルコシンの収率は97.8質量%、遊離脂肪酸含量は2.1質量%、純度は97.9質量%、色相はガードナーで4であった。
(Solvent distillation step)
The separated and obtained organic phase was distilled under reduced pressure at 60 ° C. under a pressure of 30 mmHg.
The yield of the obtained N-oleoyl sarcosine was 97.8% by mass, the free fatty acid content was 2.1% by mass, the purity was 97.9% by mass, and the hue was 4 by Gardner.
〔実施例2〕
使用する有機溶媒をテルピネオール(Pow=2.98)に変更した以外は実施例1のアシル化工程、分層工程、水洗工程と同じ方法で実施した。溶媒留去工程は、分離取得した有機相を圧力10mmHgの下、80℃で減圧蒸留を行った。
得られたN−オレオイルザルコシンの収率は96.5質量%、遊離脂肪酸含量は4.7質量%、純度は95.3質量%、色相はガードナーで4であった。
[Example 2]
It implemented by the same method as the acylation process of Example 1, a layer separation process, and the water washing process except having changed the organic solvent to be used into terpineol ( Pow = 2.98). In the solvent distillation step, the separated and obtained organic phase was distilled under reduced pressure at 80 ° C. under a pressure of 10 mmHg.
The yield of the obtained N-oleoyl sarcosine was 96.5% by mass, the free fatty acid content was 4.7% by mass, the purity was 95.3% by mass, and the hue was 4 by Gardner.
〔実施例3〕
(アシル化工程)
37質量%のN−メチル−β−アラニンナトリウム水溶液126.8g(0.38mol)、水120.3g、24質量%の水酸化ナトリウム水溶液43.4g(水酸化ナトリウム0.26mol )、トルエン(Pow=2.69)24.1gの混合溶液に、冷却しながらオレイン酸クロリド54.0g(0.18mol)を30分間かけて滴下した。その後、30℃で15分間反応させ、24質量%の水酸化ナトリウム水溶液43.4g(水酸化ナトリウム0.26mol)を加え、冷却しながらオレイン酸クロリド54.0g(0.18mol)を30分間かけて滴下し、その後30℃で15分間反応させた。本アシル化工程における反応液のpHは11〜14であった。
Example 3
(Acylation step)
37 mass% N-methyl-β-alanine sodium aqueous solution 126.8 g (0.38 mol), water 120.3 g, 24 mass% sodium hydroxide aqueous solution 43.4 g (sodium hydroxide 0.26 mol), toluene (P ow = 2.69) 54.0 g (0.18 mol) of oleic acid chloride was dropped into the mixed solution of 24.1 g over 30 minutes while cooling. Thereafter, the mixture is reacted at 30 ° C. for 15 minutes, 43.4 g of a 24 mass% sodium hydroxide aqueous solution (0.26 mol of sodium hydroxide) is added, and 54.0 g (0.18 mol) of oleic acid chloride is added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.
(分層工程)
実施例1と同じ方法で実施した。
(Layer separation process)
The same method as in Example 1 was performed.
(水洗工程)
分離した有機相に5.5質量%のクエン酸水溶液139.2gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置すると、有機相と水相とに分層した。分離した有機相に5.5質量%のクエン酸水溶液139.2gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置させて有機相と水相とに分層した後、有機相を分離した。
(Washing process)
To the separated organic phase was added 139.2 g of an aqueous 5.5% by mass citric acid solution, and the mixture was stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase was added 139.2 g of an aqueous 5.5% by mass citric acid solution, and the mixture was stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.
(溶媒留去工程)
実施例1 と同じ方法で実施した。
得られたN−オレオイル−N−メチル−β−アラニンの収率は97.1質量%、遊離脂肪酸含量は2.8質量%、純度は97.2質量%、色相はガードナーで4であった。
(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of N-oleoyl-N-methyl-β-alanine obtained was 97.1% by mass, the free fatty acid content was 2.8% by mass, the purity was 97.2% by mass, and the hue was 4 by Gardner. It was.
〔実施例4〕
(アシル化工程)
40質量%のザルコシンナトリウム水溶液138.7g(0.50mol)、水167.7g、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)、トルエン(Pow=2.69)33.6gの混合溶液に、冷却しながらパルミチン酸クロリド66.0g(0.24mol)を30分間かけて滴下した。その後、30℃で15分間反応させ、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)を加え、冷却しながらパルミチン酸クロリド66.0g(0.24mol)を30分間かけて滴下し、その後30℃で15分間反応させた。本アシル化工程における反応液のpHは11〜14であった。
Example 4
(Acylation step)
138.7 g (0.50 mol) of 40% by weight aqueous sarcosine sodium solution, 167.7 g of water, 57.9 g of 24% by weight aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), toluene (P ow = 2.69) ) 66.0 g (0.24 mol) of palmitic acid chloride was added dropwise to the 33.6 g mixed solution over 30 minutes while cooling. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% sodium hydroxide aqueous solution (0.35 mol of sodium hydroxide) was added, and 66.0 g (0.24 mol) of palmitic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.
(分層工程)
実施例1と同じ方法で実施した。
(Layer separation process)
The same method as in Example 1 was performed.
(水洗工程)
分離した有機相に5.5質量%のクエン酸水溶液166.9gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置すると、有機相と水相とに分層した。分離した有機相に5.5質量%のクエン酸水溶液166.9gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置させて有機相と水相とに分層した後、有機相を分離した。
(Washing process)
To the separated organic phase, 5.5 wt% citric acid aqueous solution (166.9 g) was added and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase, 5.5 wt% citric acid aqueous solution (166.9 g) was added and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.
(溶媒留去工程)
実施例1と同じ方法で実施した。
得られたN−パルミトイルザルコシンの収率は96.2質量%、遊離脂肪酸含量は4.9質量%、純度は95.1質量%、色相はガードナーで3であった。
(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-palmitoyl sarcosine was 96.2% by mass, the free fatty acid content was 4.9% by mass, the purity was 95.1% by mass, and the hue was 3 by Gardner.
〔実施例5〕
(アシル化工程)
ザルコシン44.5g(0.50mol)、水178.6g、24質量%の水酸化ナトリウム水溶液141.6g(水酸化ナトリウム0.85mol)、トルエン(Pow=2.69)33.6gの混合溶液に、冷却しながらエルカ酸クロリド85.7g(0.24mol)を30分間かけて滴下した。その後、30℃で15分間反応させ、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)を加え、冷却しながらエルカ酸クロリド85.7g(0.24mol)を30分間かけて滴下し、その後30℃で15分間反応させた。本アシル化工程における反応液のpHは11〜14であった。
Example 5
(Acylation step)
A mixed solution of 44.5 g (0.50 mol) of sarcosine, 178.6 g of water, 141.6 g of a 24% by mass aqueous sodium hydroxide solution (0.85 mol of sodium hydroxide), and 33.6 g of toluene (P ow = 2.69) While cooling, 85.7 g (0.24 mol) of erucic acid chloride was added dropwise over 30 minutes. Thereafter, the mixture is reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) is added, and 85.7 g (0.24 mol) of erucic acid chloride is added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.
(分層工程)
実施例1と同じ方法で実施した。
(Layer separation process)
The same method as in Example 1 was performed.
(水洗工程)
分離した有機相に5.5質量%のクエン酸水溶液202.7gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置すると、有機相と水相とに分層した。分離した有機相に5.5質量%のクエン酸水溶液202.7gを加えて15分間攪拌した。攪拌停止後、30分間70℃で静置させて有機相と水相とに分層した後、有機相を分離した。
(Washing process)
To the separated organic phase was added 202.7 g of an aqueous 5.5% by mass citric acid solution and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase. To the separated organic phase was added 202.7 g of an aqueous 5.5% by mass citric acid solution and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 70 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.
(溶媒留去工程)
実施例1と同じ方法で実施した。
得られたN−エルカロイルザルコシンの収率は96.7質量%、遊離脂肪酸含量は4.4質量%、純度は95.6質量%、色相はガードナーで4であった。
(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-ercaroyl sarcosine was 96.7% by mass, the free fatty acid content was 4.4% by mass, the purity was 95.6% by mass, and the hue was 4 by Gardner.
〔比較例1〕
(アシル化工程)
40質量%のザルコシンナトリウム水溶液138.7g(0.50mol)、水167.7g、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)、アセトン(Pow=−0.24)33.6gの混合溶液に、冷却しながらオレイン酸クロリド72.1g(0.24mol)を30分間かけて滴下した。その後、30℃で15分間反応させ、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)を加え、冷却しながらオレイン酸クロリド72.1g(0.24mol)を30分間かけて滴下し、その後30℃で15分間反応させた。本アシル化工程における反応液のpHは11〜14であった。
[Comparative Example 1]
(Acylation step)
138.7 g (0.50 mol) of 40% by mass aqueous sodium sarcosine solution, 167.7 g of water, 57.9 g of 24% by mass aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), acetone (P ow = −0.0. 24) 72.1 g (0.24 mol) of oleic acid chloride was added dropwise to the mixed solution of 33.6 g over 30 minutes while cooling. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) was added, and 72.1 g (0.24 mol) of oleic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.
(分層工程)
62.5質量%の硫酸水溶液を滴下して溶液のpHを2にし、また溶液の温度を70℃に調整した。滴下終了後、攪拌を停止し、1時間80℃で静置すると、有機相と水相とに分層し、これから有機相を分離した。
(Layer separation process)
A 62.5 mass% sulfuric acid aqueous solution was dropped to adjust the pH of the solution to 2 and the temperature of the solution was adjusted to 70 ° C. After completion of the dropwise addition, stirring was stopped and the mixture was allowed to stand at 80 ° C. for 1 hour, so that the organic phase and the aqueous phase were separated, and the organic phase was separated therefrom.
(水洗工程)
分離した有機相に5.5質量%のクエン酸水溶液150.3gを加えて15分間攪拌した。攪拌停止後、1時間80℃で静置すると、有機相と水相とに分層した。分離した有機相に5.5質量%のクエン酸水溶液150.3gを加えて15分間攪拌した。攪拌停止後、1時間80℃で静置させて有機相と水相とに分層した後、有機相を分離した。
(Washing process)
To the separated organic phase, 150.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. When the stirring was stopped, the mixture was allowed to stand at 80 ° C. for 1 hour, and the organic phase and the aqueous phase were separated. To the separated organic phase, 150.3 g of an aqueous 5.5% by mass citric acid solution was added and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 80 ° C. for 1 hour to separate into an organic phase and an aqueous phase, and then the organic phase was separated.
(溶媒留去工程)
実施例1と同じ方法で実施した。
得られたN−オレオイルザルコシンの収率は92.5質量%、遊離脂肪酸含量は6.5質量%、純度は93.5質量%、色相はガードナーで5であった。
(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-oleoyl sarcosine was 92.5% by mass, the free fatty acid content was 6.5% by mass, the purity was 93.5% by mass, and the hue was 5 by Gardner.
〔比較例2〕
使用する有機溶媒をターシャリーブタノール(Pow=0.37)に変更した以外は比較例1と同じ方法でN−オレオイルザルコシンを得た。得られたN−オレオイルザルコシンの収率は91.6質量%、遊離脂肪酸含量は7.2質量%、純度は92.8質量%、色相はガードナーで5であった。
[Comparative Example 2]
N-oleoyl sarcosine was obtained in the same manner as in Comparative Example 1 except that the organic solvent used was changed to tertiary butanol (P ow = 0.37). The yield of the obtained N-oleoyl sarcosine was 91.6% by mass, the free fatty acid content was 7.2% by mass, the purity was 92.8% by mass, and the hue was 5 by Gardner.
〔比較例3〕
(アシル化工程)
40質量%のザルコシンナトリウム水溶液138.7g(0.50mol)、水167.7g、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)、1,2-ジクロロエタン(Pow=1.48)33.6gの混合溶液に、冷却しながらオレイン酸クロリド72.1g(0.24mol)を30分間かけて滴下した。その後、30℃で15分間反応させ、24質量%の水酸化ナトリウム水溶液57.9g(水酸化ナトリウム0.35mol)を加え、冷却しながらオレイン酸クロリド72.1g(0.24mol)を30分間かけて滴下し、その後30℃で15分間反応させた。本アシル化工程における反応液のpHは11〜14であった。
[Comparative Example 3]
(Acylation step)
138.7 g (0.50 mol) of 40% by weight aqueous sarcosine sodium solution, 167.7 g of water, 57.9 g of 24% by weight aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide), 1,2-dichloroethane (P ow = 1.48) 72.1 g (0.24 mol) of oleic acid chloride was added dropwise to 33.6 g of the mixed solution over 30 minutes while cooling. Thereafter, the mixture was reacted at 30 ° C. for 15 minutes, 57.9 g of a 24 mass% aqueous sodium hydroxide solution (0.35 mol of sodium hydroxide) was added, and 72.1 g (0.24 mol) of oleic acid chloride was added over 30 minutes while cooling. And then reacted at 30 ° C. for 15 minutes. The pH of the reaction solution in this acylation step was 11-14.
(分層工程)
62.5質量%の硫酸水溶液を滴下して溶液のpHを2にし、また溶液の温度を70℃に調整した。滴下終了後、攪拌を停止し、30分間70℃で静置すると、有機相と水相とに分層し、これから有機相を分離した。
(Layer separation process)
A 62.5 mass% sulfuric acid aqueous solution was dropped to adjust the pH of the solution to 2 and the temperature of the solution was adjusted to 70 ° C. After completion of the dropwise addition, stirring was stopped and the mixture was allowed to stand at 70 ° C. for 30 minutes, so that the organic phase and the aqueous phase were separated, and the organic phase was separated therefrom.
(水洗工程)
分離した有機相に5.5質量%のクエン酸水溶液178.8gを加えて15分間攪拌した。攪拌停止後、30分間80℃で静置すると、有機相と水相とに分層した。分離した有機相に5.5質量%のクエン酸水溶液178.8gを加えて15分間攪拌した。攪拌停止後、30分間80℃で静置させて有機相と水相とに分層した後、有機相を分離した。
(Washing process)
178.8 g of 5.5 mass% citric acid aqueous solution was added to the separated organic phase and stirred for 15 minutes. After the stirring was stopped, the mixture was allowed to stand at 80 ° C. for 30 minutes, and the organic phase and the aqueous phase were separated. 178.8 g of 5.5 mass% citric acid aqueous solution was added to the separated organic phase and stirred for 15 minutes. After stopping stirring, the mixture was allowed to stand at 80 ° C. for 30 minutes to separate into an organic phase and an aqueous phase, and then the organic phase was separated.
(溶媒留去工程)
実施例1と同じ方法で実施した。
得られたN−オレオイルザルコシンの収率は91.0質量%、遊離脂肪酸含量は6.8質量%、純度は93.2質量%、色相はガードナーで4であった。
(Solvent distillation step)
The same method as in Example 1 was performed.
The yield of the obtained N-oleoyl sarcosine was 91.0% by mass, the free fatty acid content was 6.8% by mass, the purity was 93.2% by mass, and the hue was 4 by Gardner.
〔比較例4〕
使用する有機溶媒をメチルシクロヘキサン(Pow=3.61)に変更した以外は実施例1と同じ方法でN−オレオイルザルコシンを得た。得られたN−オレオイルザルコシンの収率は89.7質量%、遊離脂肪酸含量は43.1質量%、純度は56.9質量%、色相はガードナーで4であった。
[Comparative Example 4]
N-oleoyl sarcosine was obtained in the same manner as in Example 1 except that the organic solvent used was changed to methylcyclohexane (P ow = 3.61). The yield of the obtained N-oleoyl sarcosine was 89.7% by mass, the free fatty acid content was 43.1% by mass, the purity was 56.9% by mass, and the hue was 4 by Gardner.
以上の結果に関し、使用した有機溶媒、アミノ酸、脂肪酸クロライド、各種分析値を表3にまとめた。なお、使用したアミノ酸と式(1)中の各種記号との関係を表2に示す。 Table 3 summarizes the organic solvent, amino acid, fatty acid chloride, and various analysis values used for the above results. Table 2 shows the relationship between the amino acids used and the various symbols in formula (1).
実施例1〜5はいずれの項目においても良好な結果であった。
一方、比較例は1〜3は使用した有機溶媒のPowが1.6未満であるために純度低下や色相の悪化が起こり、比較例4は使用した有機溶媒のPowが3.5よりも大きいために収率低下や純度低下が起こった。
Examples 1-5 were good results in all items.
On the other hand, in Comparative Examples 1 to 3, Pow of the organic solvent used was less than 1.6, so the purity decreased and the hue deteriorated. In Comparative Example 4, Pow of the organic solvent used was 3.5. As a result, the yield and purity decreased.
Claims (1)
An amino acid represented by the formula (1) and a fatty acid chloride having 16 to 22 carbon atoms are subjected to alkaline conditions in a mixed solvent of an organic solvent and water having an octanol / water partition coefficient of 1.6 to 3.5. And a method for producing an N-acylamino acid, characterized by carrying out an acylation reaction.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015094823A JP6507832B2 (en) | 2015-05-07 | 2015-05-07 | Method for producing N-acyl amino acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015094823A JP6507832B2 (en) | 2015-05-07 | 2015-05-07 | Method for producing N-acyl amino acid |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016210717A true JP2016210717A (en) | 2016-12-15 |
JP6507832B2 JP6507832B2 (en) | 2019-05-08 |
Family
ID=57549307
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015094823A Active JP6507832B2 (en) | 2015-05-07 | 2015-05-07 | Method for producing N-acyl amino acid |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6507832B2 (en) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4993521A (en) * | 1973-01-08 | 1974-09-05 | ||
JPS5119717A (en) * | 1974-08-09 | 1976-02-17 | Sugai Chemical Ind Co Ltd | N omega ashirukaenkiseiaminosanno seizoho |
JPS5612353A (en) * | 1979-06-25 | 1981-02-06 | Squibb & Sons Inc | Compound useful as collagenase inhibitor |
JPS632962A (en) * | 1986-01-24 | 1988-01-07 | Kawaken Fine Chem Co Ltd | Production of n-long-chain acylamino acid type surface active agent and liquid detergent composition containing said active agent |
WO1991012229A1 (en) * | 1990-02-12 | 1991-08-22 | National Research Council Of Canada | Process for preparing acyl derivatives of acylatable compounds |
JPH0597787A (en) * | 1991-10-09 | 1993-04-20 | Kao Corp | Method for producing n-long-chain acylaminocarboxylic acid or n-long-chain acylaminosulfonic acid type surfactant and cleaner composition containing the same surfactant |
JPH06157440A (en) * | 1992-11-24 | 1994-06-03 | Kao Corp | Method for separating and purifying n-long chain acylamino acid |
-
2015
- 2015-05-07 JP JP2015094823A patent/JP6507832B2/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4993521A (en) * | 1973-01-08 | 1974-09-05 | ||
JPS5119717A (en) * | 1974-08-09 | 1976-02-17 | Sugai Chemical Ind Co Ltd | N omega ashirukaenkiseiaminosanno seizoho |
JPS5612353A (en) * | 1979-06-25 | 1981-02-06 | Squibb & Sons Inc | Compound useful as collagenase inhibitor |
JPS632962A (en) * | 1986-01-24 | 1988-01-07 | Kawaken Fine Chem Co Ltd | Production of n-long-chain acylamino acid type surface active agent and liquid detergent composition containing said active agent |
WO1991012229A1 (en) * | 1990-02-12 | 1991-08-22 | National Research Council Of Canada | Process for preparing acyl derivatives of acylatable compounds |
JPH0597787A (en) * | 1991-10-09 | 1993-04-20 | Kao Corp | Method for producing n-long-chain acylaminocarboxylic acid or n-long-chain acylaminosulfonic acid type surfactant and cleaner composition containing the same surfactant |
JPH06157440A (en) * | 1992-11-24 | 1994-06-03 | Kao Corp | Method for separating and purifying n-long chain acylamino acid |
Also Published As
Publication number | Publication date |
---|---|
JP6507832B2 (en) | 2019-05-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5440556B2 (en) | High-purity trialkylgallium and its production method | |
US10752569B2 (en) | Process for the manufacture of 2,6-dimethyl-5-hepten-1-al | |
JP5581324B2 (en) | Process for producing N, N-dialkyllactamides | |
EP0030528B1 (en) | Process for the introduction of alkyl, aralkyl or cycloalkyl groups onto a functional group-substituted carbon chain | |
JP2016210717A (en) | Production process for n-acylamino acid | |
JP6952974B2 (en) | Method for producing amide compound | |
JP2008037852A (en) | METHOD FOR PRODUCING omega-BROMO LONG-CHAIN CARBOXYLIC ACID | |
JP2008050268A (en) | High-purity trialkylgallium and method for producing the same | |
EP0648731A1 (en) | Process for hydroxycarbonylation of butadiene | |
JP2008184419A (en) | High-purity trialkylindium and its production method | |
JP5348186B2 (en) | High-purity trialkylgallium and its production method | |
JP2014214152A (en) | Method for producing asymmetric dialkylamine compound | |
JP2014162758A (en) | Method for producing high purity dialkyl tartrate | |
EP2855422B1 (en) | Synthesis of diamido gellants by using dane salts of amino acids | |
JPH0436258A (en) | Production of alkylketene dimer | |
EP0301925B1 (en) | Process for the enantiospecific preparation of (s)2-ethyl amino-1-3-(trifluoromethyl phenyl) propane | |
JPH0436259A (en) | Production of alkylketene dimer | |
JP6556476B2 (en) | Difluoromethylzinc compound | |
JPH0128009B2 (en) | ||
JPH0142253B2 (en) | ||
RU2612956C1 (en) | Method for producing 1-adamantyl acetaldehyde | |
JPS5946255A (en) | Preparation of 2-alkoxymethylene-3,3-dialkoxy- propanenitriles | |
JP4873207B2 (en) | Method for purifying optically active carboxylic acid chloride | |
JP3852529B2 (en) | Method for producing nitrogen-containing compound | |
KR101621754B1 (en) | PROCESS OF PREPARING α-KETO (CYANOMETHYLENE)TRIPHENYLPHOSPHORANES USING XANTHATE COMPOUNDS |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180226 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190130 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190212 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190220 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190305 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190318 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6507832 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |