JPH0451552B2 - - Google Patents
Info
- Publication number
- JPH0451552B2 JPH0451552B2 JP12068584A JP12068584A JPH0451552B2 JP H0451552 B2 JPH0451552 B2 JP H0451552B2 JP 12068584 A JP12068584 A JP 12068584A JP 12068584 A JP12068584 A JP 12068584A JP H0451552 B2 JPH0451552 B2 JP H0451552B2
- Authority
- JP
- Japan
- Prior art keywords
- yield
- benzylidenehydantoin
- reaction
- hydantoin
- alanine
- 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.)
- Expired
Links
- UDTSPKADQGPZFS-SOFGYWHQSA-N (5e)-5-benzylideneimidazolidine-2,4-dione Chemical compound N1C(=O)NC(=O)\C1=C/C1=CC=CC=C1 UDTSPKADQGPZFS-SOFGYWHQSA-N 0.000 claims description 16
- UDTSPKADQGPZFS-UHFFFAOYSA-N 1/7/3775 Natural products N1C(=O)NC(=O)C1=CC1=CC=CC=C1 UDTSPKADQGPZFS-UHFFFAOYSA-N 0.000 claims description 16
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 13
- 229940091173 hydantoin Drugs 0.000 claims description 13
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 6
- 150000001413 amino acids Chemical class 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 9
- 235000004279 alanine Nutrition 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 229960005190 phenylalanine Drugs 0.000 description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-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
- 229940000635 beta-alanine Drugs 0.000 description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 150000001469 hydantoins Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000011118 potassium hydroxide Nutrition 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- 229960003080 taurine Drugs 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- FMGRPEQSMWQKHM-QTNFYWBSSA-N (2s)-2-aminopentanedioic acid;sodium;hydrate Chemical compound O.[Na].OC(=O)[C@@H](N)CCC(O)=O FMGRPEQSMWQKHM-QTNFYWBSSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CKTUXQBZPWBFDX-UHFFFAOYSA-N 3-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCCC(C(O)=O)C1 CKTUXQBZPWBFDX-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- -1 alkaline earth metal salts Chemical class 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- UEKDRLRXXAOOFP-UHFFFAOYSA-N imidazolidine-2,4-dione Chemical compound O=C1CNC(=O)N1.O=C1CNC(=O)N1 UEKDRLRXXAOOFP-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
Description
【発明の詳細な説明】
本発明は、５−ベンジリデンヒダントインの製
法方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 5-benzylidenehydantoin.
５−ベンジリデンヒダントインはフエニルアラ
ニンを製造するための重要な中間体である。 5-Benzylidenehydantoin is an important intermediate for producing phenylalanine.
アルデヒド類とヒダントイン類を縮合させて５
−置換ヒダントイン類を製造する反応は、
Wheeler−Hoffman反応と呼ばれ、公知である
（J.Am.Chem.Soc.、45369（1911））。この方法で
は反応は酢酸及び無水酢酸ナトリウムの存在下で
行なわれる。また、この反応についての別の詳細
な例は、Org.Syn.、Coll.Vol.5627に記載されて
おり、反応は無水ピペラジン中で行なわれてい
る。これらの方法は、いずれも高価な有機溶媒を
使用しており、また収率も70％程度と低いため
に、工業的に満足すべきものではない。 By condensing aldehydes and hydantoins, 5
-The reaction for producing substituted hydantoins is
It is called the Wheeler-Hoffman reaction and is well known (J. Am. Chem. Soc., 45369 (1911)). In this method the reaction is carried out in the presence of acetic acid and anhydrous sodium acetate. Another detailed example of this reaction is also described in Org. Syn., Coll. Vol. 5627, where the reaction is carried out in anhydrous piperazine. All of these methods use expensive organic solvents and yields are as low as about 70%, so they are not industrially satisfactory.
本発明は、ベンズアルデヒドをグリシン以外の
アミノ酸又はその塩の存在下、PH８〜12の範囲で
ヒダントイン（２，４−イミダゾリジンジオン）
と反応させることにより、工業的に有利に５−ベ
ンジリデンヒダントインを製造する方法を提供す
るものである。本発明によれば、水系の溶媒中
で、比較的短かい反応時間内に結晶性の良い５−
ベンジリデンヒダントインを好収率で得ることが
できる。 In the present invention, benzaldehyde is converted into hydantoin (2,4-imidazolidinedione) at a pH range of 8 to 12 in the presence of an amino acid other than glycine or a salt thereof.
The object of the present invention is to provide an industrially advantageous method for producing 5-benzylidenehydantoin by reacting with 5-benzylidenehydantoin. According to the present invention, in an aqueous solvent, 5-5-
Benzylidenehydantoin can be obtained in good yield.
本発明で使用される反応溶媒としては、一般に
水が用いられるが、水のみならず、必要に応じて
メタノール，エタノール，ジオキサンなどの水に
可溶な有機溶媒を水を混合したものを使用するこ
ともできる。 Water is generally used as the reaction solvent in the present invention, but not only water but also water mixed with a water-soluble organic solvent such as methanol, ethanol, dioxane, etc., may be used as necessary. You can also do that.
使用するアミノ酸としては、グルタミン酸，ア
スパラギン酸，リジン，アルギニン，オルニチ
ン，α−アラニン，ロイシン，イソロイシン，バ
リン，β−アラニン，フエニルアラニン，チロシ
ン，ドーパ，フエニルグリシン，セリン，スレオ
ニン，メチオニン，タウリン，Ｓ−カルボキシメ
チルシステイン，γ−アミノ酪酸，トラネキサム
酸，３−アミノシクロヘキサンカルボン酸を単独
に、又は混合して使用できる。また、これらアミ
ノ酸の塩、例えばアルカリ金属，アルカリ土類金
属塩や鉱酸塩等を用いることもできる。これらの
使用量はヒダントインに対して0.1〜２モル比、
好ましくは0.3〜１モル比が良い。少ないと効果
が少なく、また多く使用しても、それに見合う効
果は得られず、経済的でない。 Amino acids used include glutamic acid, aspartic acid, lysine, arginine, ornithine, α-alanine, leucine, isoleucine, valine, β-alanine, phenylalanine, tyrosine, dopa, phenylglycine, serine, threonine, methionine, and taurine. , S-carboxymethylcysteine, γ-aminobutyric acid, tranexamic acid, and 3-aminocyclohexanecarboxylic acid can be used alone or in combination. Furthermore, salts of these amino acids, such as alkali metal or alkaline earth metal salts or mineral acid salts, can also be used. The amount used is 0.1 to 2 molar ratio to hydantoin,
Preferably, the molar ratio is 0.3 to 1. If the amount is too small, the effect will be low, and even if the amount is used in large amount, the corresponding effect will not be obtained and it is not economical.
反応時のPHは８〜12、好ましくは９〜10が良
い。アミノ酸を中性ないし酸性で使用しても効果
は得られず、上記PHに反応液PHを調製する必要が
ある。PHの調製に使用するアルカリの種類として
は、特に制限はなく、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，炭酸カリウム
などのアルカリ金属水酸化物およびそれらの炭酸
塩，水酸化マグネシウム，水酸化カルシウム等の
アルカリ土類金属水酸化物等が使用できる。 The pH during the reaction is preferably 8 to 12, preferably 9 to 10. Even if the amino acid is used in a neutral or acidic state, no effect is obtained, and it is necessary to adjust the pH of the reaction solution to the above-mentioned pH. There are no particular restrictions on the type of alkali used to prepare the PH; for example, sodium hydroxide,
Alkali metal hydroxides such as potassium hydroxide, sodium carbonate, and potassium carbonate, and their carbonates, and alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide can be used.
反応温度及び時間については、必ずしも厳密な
制限はないが、通常は40〜100℃好ましくは60〜
80℃であり、１〜10時間、好ましくは２〜５時間
である。 There are no strict restrictions on the reaction temperature and time, but it is usually 40-100°C, preferably 60-100°C.
The temperature is 80°C for 1 to 10 hours, preferably 2 to 5 hours.
反応生成物である５−ベンジリデンヒダントイ
ンは水に難溶性であるので、反応の進行と共に結
晶として析出するので遠心分離等の方法により、
容易に分離回収することができる。 Since the reaction product 5-benzylidenehydantoin is poorly soluble in water, it precipitates as crystals as the reaction progresses, so it can be removed by methods such as centrifugation.
It can be easily separated and recovered.
以下実施例によつて、本発明の方法について更
に具体的に説明する。但し、これらは説明のため
の単なる例示であり、本発明は、これらの例に何
ら制限されない。 The method of the present invention will be explained in more detail below with reference to Examples. However, these are merely examples for explanation, and the present invention is not limited to these examples in any way.
実施例 １
温度計，還流冷却器，攪拌機を備えた３つ口
500mlセパラブルフラスコを恒温槽中にセツトし
た。Example 1 Three ports equipped with thermometer, reflux condenser, and stirrer
A 500ml separable flask was placed in a thermostatic bath.
水200ml、ヒダントイン50.5ｇ（＝0.50mol），
アラニン22.3ｇ（＝0.25mol），固型カセイソーダ
5.0ｇ（＝0.125mol），ベンズアルデヒド53.0ｇ
（＝0.50mol）を入れ、昇温し、80℃にて２時間
攪拌した。この間反応液のPHは9.8〜9.6であつ
た。室温まで冷却した後、反応液を遠心分離によ
り５−ベンジリデンヒダントイン87.0ｇを得た。
ヒダントインに対し92.6％の収率であつた。 200ml of water, 50.5g of hydantoin (=0.50mol),
Alanine 22.3g (=0.25mol), solid caustic soda
5.0g (=0.125mol), benzaldehyde 53.0g
(=0.50 mol), the temperature was raised, and the mixture was stirred at 80°C for 2 hours. During this time, the pH of the reaction solution was 9.8 to 9.6. After cooling to room temperature, the reaction solution was centrifuged to obtain 87.0 g of 5-benzylidenehydantoin.
The yield was 92.6% based on hydantoin.
実施例 ２
実施例１のアラニンのかわりに、Ｌ−グルタミ
ン酸ソーダ・−水塩46.8ｇ（＝0.25mol）を使用
し、同様に反応させた。この間反応液のPHは9.8
〜9.5であつた。５−ベンジリデンヒダントイン
の収量82.5ｇ。ヒダントインに対し、87.8％の収
率であつた。Example 2 In place of alanine in Example 1, 46.8 g (=0.25 mol) of L-glutamic acid sodium hydrate was used, and the reaction was carried out in the same manner. During this time, the pH of the reaction solution was 9.8.
It was ~9.5. Yield of 5-benzylidenehydantoin: 82.5 g. The yield was 87.8% based on hydantoin.
実施例 ３
実施例１のアラニンのかわりに、Ｌ−リジン塩
酸塩45.7ｇ（＝0.25mol）を使用し、カセイカリ
によりPH調製して同様に反応させた。この間反応
液のPHは9.6〜9.3であつた。５−ベンジリデンヒ
ダントインの収量86.6ｇ。ヒダントインに対し、
92.1％の収率であつた。Example 3 In place of alanine in Example 1, 45.7 g (=0.25 mol) of L-lysine hydrochloride was used, the pH was adjusted with caustic potash, and the reaction was carried out in the same manner. During this time, the pH of the reaction solution was 9.6 to 9.3. Yield of 5-benzylidenehydantoin: 86.6 g. For hydantoin,
The yield was 92.1%.
実施例 ４
実施例１のアラニンのかわりに、β−アラニン
13.3ｇ（＝0.15mol）を使用し、水酸化カルシウ
ムでPH調製し同様に反応させた。この間、反応液
のPHは9.9〜9.7であつた。５−ベンジリデンヒダ
ントインの収量79.5ｇ。ヒダントインに対し84.6
％の収率であつた。Example 4 β-alanine was used instead of alanine in Example 1.
Using 13.3 g (=0.15 mol), the pH was adjusted with calcium hydroxide and the reaction was carried out in the same manner. During this time, the pH of the reaction solution was 9.9 to 9.7. Yield of 5-benzylidenehydantoin: 79.5 g. 84.6 for hydantoin
% yield.
実施例 ５
実施例１のアラニンのかわりに、Ｌ−フエニル
アラニン41.3ｇ（＝0.25mol）を使用し、同様に
10時間反応させた。この間、反応液のPHは9.7〜
9.4であつた。５−ベンジリデンヒダントインの
収量77.0ｇ。ヒダントインに対し、81.9％の収率
であつた。Example 5 In place of alanine in Example 1, 41.3 g (=0.25 mol) of L-phenylalanine was used, and the same procedure was carried out.
The reaction was allowed to proceed for 10 hours. During this time, the pH of the reaction solution was 9.7~
It was 9.4. Yield of 5-benzylidenehydantoin: 77.0 g. The yield was 81.9% based on hydantoin.
実施例 ６
実施例１のアラニンのかわりにＬ−セリン42.1
ｇ（＝0.40mol）を使用し、同様に反応させた。
この間、反応液のPHは9.1〜8.9であつた。５−ベ
ンジリデンヒダントインの収量75.4ｇ。ヒダント
インに対し、80.2％の収率であつた。Example 6 L-serine 42.1 instead of alanine in Example 1
g (=0.40 mol) was used and reacted in the same manner.
During this time, the pH of the reaction solution was 9.1 to 8.9. Yield of 5-benzylidenehydantoin: 75.4 g. The yield was 80.2% based on hydantoin.
実施例 ７
実施例１のアラニンのかわりにタウリン31.3ｇ
（＝0.25mol）を使用し、同様に反応させた。こ
の間、反応液のPHは9.5〜9.3であつた。５−ベン
ジリデンヒダントインの収量82.7ｇ。ヒダントイ
ンに対し、88.0％の収率であつた。Example 7 31.3g of taurine instead of alanine in Example 1
(=0.25 mol) and reacted in the same manner. During this time, the pH of the reaction solution was 9.5 to 9.3. Yield of 5-benzylidenehydantoin: 82.7 g. The yield was 88.0% based on hydantoin.
比較例 １
実施例１において、カセイソーダを32.0ｇ（＝
0.80mol）使用して、同様に反応させた。この
間、反応液のPHは12.5〜12.0であつた。５−ベン
ジリデンヒダントインの収量52.6ｇ。ヒダントイ
ンに対して54.0％の収率であつた。（このときHD
は消失していた。）
比較例 ２
実施例１において、カセイソーダを0.7ｇ（＝
0.018mol）使用して、同様に７時間反応させた。
この間、反応液のPHは8.0〜7.5であつた。５−ベ
ンジリデンヒダントインの収量69.7ｇ。ヒダント
インに対して74.1％の収率であつた。Comparative Example 1 In Example 1, 32.0g of caustic soda (=
0.80 mol) and reacted in the same manner. During this time, the pH of the reaction solution was 12.5 to 12.0. Yield of 5-benzylidenehydantoin: 52.6 g. The yield was 54.0% based on hydantoin. (At this time, HD
had disappeared. ) Comparative Example 2 In Example 1, 0.7g (=
0.018 mol) and reacted in the same manner for 7 hours.
During this time, the pH of the reaction solution was 8.0 to 7.5. Yield of 5-benzylidenehydantoin: 69.7 g. The yield was 74.1% based on hydantoin.
比較例 ３
実施例１においてアラニン8.9ｇ（＝0.10mol），
カセイソーダ1.0ｇ（＝0.05mol）使用して同様に
９時間反応させた。この間反応液のPHは8.1〜7.5
であつた。５−ベンジリデンヒダントインの収量
72.1ｇ。ヒダントインに対して、76.7％の収率で
あつた。Comparative Example 3 In Example 1, 8.9 g (=0.10 mol) of alanine,
A similar reaction was carried out for 9 hours using 1.0 g (=0.05 mol) of caustic soda. During this time, the pH of the reaction solution was 8.1 to 7.5.
It was hot. Yield of 5-benzylidenehydantoin
72.1g. The yield was 76.7% based on hydantoin.
Claims (1)
ンを除く）又はその塩の存在下、PH８〜12の範囲
で水性溶液中でヒダントインと反応させることを
特徴とする５−ベンジリデンヒダントインの製造
方法。1. A method for producing 5-benzylidenehydantoin, which comprises reacting benzaldehyde with hydantoin in an aqueous solution at a pH of 8 to 12 in the presence of an amino acid (excluding glycine) or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12068584A JPS611669A (en) | 1984-06-14 | 1984-06-14 | 5-benzylidenehydantoin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12068584A JPS611669A (en) | 1984-06-14 | 1984-06-14 | 5-benzylidenehydantoin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS611669A JPS611669A (en) | 1986-01-07 |
| JPH0451552B2 true JPH0451552B2 (en) | 1992-08-19 |
Family
ID=14792414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12068584A Granted JPS611669A (en) | 1984-06-14 | 1984-06-14 | 5-benzylidenehydantoin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS611669A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114957130B (en) * | 2022-06-28 | 2023-05-09 | 山东创新药物研发有限公司 | Purification method and application of high-purity 5-benzylidene hydantoin |
-
1984
- 1984-06-14 JP JP12068584A patent/JPS611669A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS611669A (en) | 1986-01-07 |
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