JPH0597814A - Method for producing 5-(hydroxymethyl) hydantoin - Google Patents
Method for producing 5-(hydroxymethyl) hydantoinInfo
- Publication number
- JPH0597814A JPH0597814A JP3255368A JP25536891A JPH0597814A JP H0597814 A JPH0597814 A JP H0597814A JP 3255368 A JP3255368 A JP 3255368A JP 25536891 A JP25536891 A JP 25536891A JP H0597814 A JPH0597814 A JP H0597814A
- Authority
- JP
- Japan
- Prior art keywords
- hydantoin
- hmh
- aldehyde
- barium hydroxide
- 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.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- CBRIRBXLTFAPOM-UHFFFAOYSA-N 5-(hydroxymethyl)imidazolidine-2,4-dione Chemical compound OCC1NC(=O)NC1=O CBRIRBXLTFAPOM-UHFFFAOYSA-N 0.000 title abstract description 3
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229940091173 hydantoin Drugs 0.000 claims abstract description 19
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims abstract description 12
- 229910001863 barium hydroxide Inorganic materials 0.000 claims abstract description 12
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 150000002576 ketones Chemical class 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 150000001469 hydantoins Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 15
- 159000000009 barium salts Chemical class 0.000 abstract description 7
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 abstract description 5
- 239000002253 acid Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000003115 biocidal effect Effects 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 230000008030 elimination Effects 0.000 abstract description 2
- 238000003379 elimination reaction Methods 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- -1 telomycin Chemical class 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- 238000004566 IR spectroscopy Methods 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- QVQLCTNNEUAWMS-UHFFFAOYSA-N barium oxide Chemical compound [Ba]=O QVQLCTNNEUAWMS-UHFFFAOYSA-N 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000203 mixture Substances 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
- 238000010992 reflux Methods 0.000 description 2
- 108010073246 telomycin Proteins 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical compound O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000004689 octahydrates Chemical class 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 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
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、抗生物質テロマイシン
等の中間体であるβ‐ヒドロキシアミノ酸を製造するた
めの中間体として有用な５‐（ヒドロキシメチル）ヒダ
ントイン誘導体（以下、５‐ＨＭＨと略記する）の製造
方法に関する。TECHNICAL FIELD The present invention relates to a 5- (hydroxymethyl) hydantoin derivative (hereinafter referred to as 5-HMH) useful as an intermediate for producing β-hydroxyamino acid which is an intermediate for the antibiotic telomycin and the like. Abbreviated).
【０００２】[0002]
【従来の技術】β‐ヒドロキシアミノ酸は、抗生物質テ
ロマイシン等の構成アミノ酸であり、５‐ＨＭＨを加水
分解することにより得られる。この５‐ＨＭＨはヒダン
トインとアルデヒドまたはケトンを１級または２級アミ
ンの存在下で加熱することにより得られる５‐アルキリ
デンヒダントインの中間体として生成するが、この方法
では、５‐ＨＭＨが生成したのち、直ちに水が脱離する
ため、５‐ＨＭＨを高純度かつ高収率で得ることは困難
であった。BACKGROUND OF THE INVENTION β-Hydroxyamino acid is a constituent amino acid such as telomycin, an antibiotic, and is obtained by hydrolyzing 5-HMH. This 5-HMH is produced as an intermediate of 5-alkylidenehydantoin obtained by heating hydantoin and an aldehyde or ketone in the presence of a primary or secondary amine. However, it is difficult to obtain 5-HMH in high purity and high yield because water is immediately desorbed.
【０００３】[0003]
【発明が解決しようとする課題】本発明は、５‐ＨＭＨ
を高純度かつ高収率で製造する方法を提供することを目
的とする。SUMMARY OF THE INVENTION The present invention is a 5-HMH.
It is an object of the present invention to provide a method for producing high purity and high yield.
【０００４】[0004]
【課題を解決するための手段】本発明は、ヒダントイン
とアルデヒドからの５‐ＨＭＨの製造方法において、１
級または２級アミンに代えて水酸化バリウムを触媒に使
用することにより、５‐ＨＭＨ生成後の水の脱離を防止
でき、かつ、生成した５‐ＨＭＨがバリウム塩として単
離できるのでこれを酸で処理することにより高純度の５
‐ＨＭＨが得られるとの知見に基づきなされたものであ
る。５‐ＨＭＨの単離は本発明で初めて可能となったも
のである。The present invention provides a method for producing 5-HMH from hydantoin and an aldehyde, which comprises the steps of:
By using barium hydroxide as a catalyst in place of a secondary or secondary amine, elimination of water after formation of 5-HMH can be prevented, and the formed 5-HMH can be isolated as a barium salt. High purity of 5 by treating with acid
-This is based on the finding that HMH can be obtained. The isolation of 5-HMH was made possible for the first time by the present invention.
【０００５】即ち、本発明は、ヒダントイン及び一般式
Ｉ Ｒ1 ＣＯＲ2 Ｉ （式中、Ｒ1 及びＲ2 はそれぞれ独立して水素、炭素数
１〜１０のアルキル基、低級アルキル基で置換されてい
てもよいアリール基または低級アルキル基で置換されて
いてもよいアラルキル基を表す。）で示されるアルデヒ
ドまたはケトンを、溶媒中、水酸化バリウムの存在下で
加熱することを特徴とする、一般式IIThat is, according to the present invention, hydantoin and the general formula IR 1 COR 2 I (in the formula, R 1 and R 2 are independently substituted with hydrogen, an alkyl group having 1 to 10 carbon atoms or a lower alkyl group). Which represents an aralkyl group which may be substituted with an optionally substituted aryl group or a lower alkyl group), is heated in a solvent in the presence of barium hydroxide, Formula II
【０００６】[0006]
【化２】 （式中、Ｒ1 及びＲ2 は前記と同様。）で示される５‐
（ヒドロキシメチル）ヒダントイン誘導体（５‐ＨＭ
Ｈ）の製造方法の発明である。本発明の方法で原料とし
て使用されるヒダントインは公知の化合物であり高純度
のものが市販されているので市販品をそのまま用いれば
よい。[Chemical 2] (Wherein R 1 and R 2 are the same as above)
(Hydroxymethyl) hydantoin derivative (5-HM
It is an invention of a manufacturing method of H). Hydantoin used as a raw material in the method of the present invention is a known compound, and a high purity hydantoin is commercially available. Therefore, a commercially available product may be used as it is.
【０００７】一方、一般式Ｉで示されるアルデヒドまた
はケトンはＲ1 及びＲ2 の種類及びその組み合わせによ
り種々の化合物が可能である。ここに、Ｒ1 及びＲ2 の
例としては、例えば、メチル、エチル、プロピル、イソ
プロピル、ブチル、 sec‐ブチル、tert‐ブチル、ペン
チル、イソペンチル、ヘキシル、ヘプチル、オクチル、
エチルヘキシル、ノニル及びデシル基等炭素数１〜１０
のアルキル基、例えば、フェニル、トリル、キシリル、
クメニル、イソペンチルフェニル、ナフチル及びメチル
ナフチル基等、好ましくは炭素数６〜１２の無置換また
は低級アルキル基で置換されたアリール基、例えば、ベ
ンジル、メチルベンジル、フェネチル、プロピルフェネ
チル基等、好ましくは炭素数６〜１２の無置換または低
級アルキル基で置換されたアラルキル基が挙げられる。
これらアルデヒドまたはケトンの使用割合は特に限定さ
れないが、一般にアルデヒドまたはケトンがヒダントイ
ンより過剰であるほうがよく、好ましくはヒダントイン
１モルに対して１〜１．２モルである。On the other hand, the aldehyde or ketone represented by the general formula I can be various compounds depending on the types of R 1 and R 2 and combinations thereof. Here, examples of R 1 and R 2 include, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl,
1 to 10 carbon atoms such as ethylhexyl, nonyl and decyl groups
An alkyl group of, for example, phenyl, tolyl, xylyl,
Cumenyl, isopentylphenyl, naphthyl and methylnaphthyl groups, etc., preferably an aryl group having 6 to 12 carbon atoms and substituted with a lower alkyl group, for example, benzyl, methylbenzyl, phenethyl, propylphenethyl group, etc., preferably Examples thereof include an aralkyl group having 6 to 12 carbon atoms, which is unsubstituted or substituted with a lower alkyl group.
The ratio of these aldehydes or ketones to be used is not particularly limited, but it is generally preferable that the amount of aldehydes or ketones is in excess of hydantoin, and preferably 1 to 1.2 mols relative to 1 mol of hydantoin.
【０００８】本発明で使用する溶媒は、溶媒自身が反応
せず、かつ、反応に悪影響を及ぼさず、更に、原料及び
水酸化バリウムが反応に必要な程度に溶解し得るもので
あれば特に限定されないが、水、アルコール及びこれら
の混合溶媒が好ましく、特に水とアルコールの混合溶媒
が好ましい。また、アルコール自身も炭素数１〜４のも
のが好ましく、具体例としてはメタノール、エタノー
ル、プロパノール、イソプロパノール、ブタノール、イ
ソブタノール、 sec‐ブタノール、tert‐ブタノールが
挙げられる。水とアルコールの混合溶媒を使用する場合
の水／アルコールの容量比は好ましくは３／１〜１０／
１である。これら溶媒の使用量は、反応液が効率的に撹
拌できる量であれば特に限定されないが、通常、ヒダン
トイン及びアルデヒドまたはケトンの合計重量に対し
て、０．５〜４倍容量、好ましくは０．５〜２倍容量で
ある。The solvent used in the present invention is not particularly limited as long as the solvent itself does not react and does not adversely affect the reaction, and the raw material and barium hydroxide can be dissolved to the extent necessary for the reaction. However, water, alcohol and a mixed solvent thereof are preferable, and a mixed solvent of water and alcohol is particularly preferable. Also, the alcohol itself preferably has 1 to 4 carbon atoms, and specific examples thereof include methanol, ethanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, and tert-butanol. When using a mixed solvent of water and alcohol, the volume ratio of water / alcohol is preferably 3/1 to 10 /.
It is 1. The amount of these solvents to be used is not particularly limited as long as the reaction liquid can be efficiently stirred, but is usually 0.5 to 4 times by volume, preferably 0. 4 times the total weight of hydantoin and aldehyde or ketone. 5 to 2 times the capacity.
【０００９】本発明はヒダントインとアルデヒドまたは
ケトンの反応を水酸化バリウムの存在下で行う点に特徴
を有するものである。用いる水酸化バリウムは、無水物
または水化物のいずれであってもよく、水化物を用いる
場合には１水化物であっても８水化物であってもよい。
なお、反応溶媒に水が存在する場合には、水酸化バリウ
ムの代わりに酸化バリウムを使用して反応系内で水酸化
バリウムを生成させても差し支えない。かかる水酸化バ
リウムの使用量は、目的とする反応を促進できる量であ
れば特に限定されないが、生成物を 1/2バリウム塩とし
て単離する場合には原料ヒダントインの 1/2倍モルを用
いるのが好ましい。The present invention is characterized in that the reaction of hydantoin with an aldehyde or ketone is carried out in the presence of barium hydroxide. The barium hydroxide used may be either an anhydride or a hydrate. When a hydrate is used, it may be a monohydrate or an octahydrate.
When water is present in the reaction solvent, barium oxide may be used in place of barium hydroxide to generate barium hydroxide in the reaction system. The amount of such barium hydroxide to be used is not particularly limited as long as it can promote the desired reaction, but when the product is isolated as 1/2 barium salt, 1/2 mol of the starting hydantoin is used. Is preferred.
【００１０】本発明の方法は、上記で説明した原料、溶
媒及び水酸化バリウムを一度にまたは順次反応器に加
え、これを反応が完結するまで単に加熱するだけでよ
い。反応温度は、反応が進行しかつ生成物が分解しない
温度であれば、特に限定されるものではないが、通常は
還流温度で行われるため使用する溶媒に依存し、一般に
６０〜１３０℃、好ましくは７０〜１２０℃である。反
応時間は、使用するアルデヒドまたはケトンの種類及び
反応温度にもよるが、通常２〜６時間であり、例えば、
ブチルアルデヒドまたはベンズアルデヒドを原料として
１１０〜１２０℃で反応する場合は３時間程度となる。The process of the present invention involves adding the above-described raw materials, solvent and barium hydroxide to the reactor at once or sequentially and simply heating until the reaction is complete. The reaction temperature is not particularly limited as long as it is a temperature at which the reaction proceeds and the product does not decompose, but it is usually carried out at the reflux temperature and therefore depends on the solvent used, and generally 60 to 130 ° C., preferably Is 70 to 120 ° C. The reaction time is usually 2 to 6 hours, depending on the type of aldehyde or ketone used and the reaction temperature, and for example,
When using butyraldehyde or benzaldehyde as a raw material and reacting at 110 to 120 ° C., it takes about 3 hours.
【００１１】反応後は、水等を加えて生成物の溶解性を
低下させて冷却すれば、５‐ＨＭＨが望ましくは 1/2バ
リウム塩として析出するから、これを常法により反応液
から分離し、塩酸等で処理すれば遊離の５‐ＨＭＨが得
られる。これを再結晶等により精製するのは任意であ
る。以下に実施例を示して本発明をより詳細に説明す
る。After the reaction, if water or the like is added to reduce the solubility of the product and the mixture is cooled, 5-HMH precipitates as a 1/2 barium salt, which is preferably separated from the reaction solution by a conventional method. If treated with hydrochloric acid or the like, free 5-HMH can be obtained. Purification by recrystallization or the like is optional. Hereinafter, the present invention will be described in more detail with reference to examples.
【００１２】[0012]
【実施例】実施例１ 還流冷却器及び撹拌装置を備えた反応器に水７５ｍｌ、
イソプロパノール２０ｍｌ、ヒダントイン５０．０ｇ
（０．５０モル）、イソブチルアルデヒド３９．７ｇ
（０．５５モル）及び水酸化バリウム８水化物７８．９
ｇ（０．２５モル）を加え、１１０℃の油浴中で３時間
還流した。反応後、水５０ｍｌを加え５℃に冷却して、
析出した白色結晶を濾取した。水洗後、４０℃で真空乾
燥して５‐（１‐ヒドロキシ‐２‐メチルプロピル）ヒ
ダントイン・1/2 バリウム塩９３．０ｇ（収率７８％）
を得た。 Example 1 75 ml of water in a reactor equipped with a reflux condenser and a stirrer,
20 ml of isopropanol, 50.0 g of hydantoin
(0.50 mol), isobutyraldehyde 39.7 g
(0.55 mol) and barium hydroxide octahydrate 78.9
g (0.25 mol) was added, and the mixture was refluxed in an oil bath at 110 ° C. for 3 hours. After the reaction, add 50 ml of water and cool to 5 ° C.
The precipitated white crystals were collected by filtration. After washing with water and vacuum drying at 40 ° C, 5- (1-hydroxy-2-methylpropyl) hydantoin 1/2 barium salt 93.0 g (yield 78%)
Got
【００１３】全量（０．３９モル）を水２３０ｍｌに懸
濁し、３５％塩酸８０．４ｇ（０．７７モル）を加え、
室温で３０分間攪拌した。スラリーから白色の結晶を分
離し、水洗後４０℃で真空乾燥し、遊離の５‐（１‐ヒ
ドロキシ‐２‐メチルプロピル）ヒダントイン５４．９
ｇ（収率８１．８％）を得、更にエタノールから再結晶
した。The whole amount (0.39 mol) was suspended in 230 ml of water, and 80.4 g (0.77 mol) of 35% hydrochloric acid was added,
Stir for 30 minutes at room temperature. White crystals were separated from the slurry, washed with water and dried in vacuo at 40 ° C. to give free 5- (1-hydroxy-2-methylpropyl) hydantoin 54.9.
g (yield 81.8%) was obtained and recrystallized from ethanol.
【００１４】質量スペクトル分析（ＦＡＢモード） 計算値（M + H + C7H13N2O3 ）：１７３．０９２６ 測定値 ：１７３．０９２０ 赤外線吸収スペクトル分析（KBr,cm-1） 3250, 2950, 1790, 1760, 1710, 1410,1280, 1205, 105
5, 1000, 740,690[0014] Mass spectrometry (FAB mode) calcd (M + H + C 7 H 13 N 2 O 3): 173.0926 Found: 173.0920 Infrared absorption spectrometry (KBr, cm -1) 3250, 2950 , 1790, 1760, 1710, 1410,1280, 1205, 105
5, 1000, 740, 690
【００１５】実施例２ 仕込み水量を７５ｍｌから１００ｍｌに増加し、イソブ
チルアルデヒド３９．７ｇ（０．５５モル）をベンズア
ルデヒド５８．４ｇ（０．５５モル）に代え、油浴温度
を１１０℃から１２０℃に上昇させた以外は実施例１と
同様に行い、５‐（１‐ヒドロキシ‐１‐フェニル）ヒ
ダントイン・1/2 バリウム塩７８．４ｇ（収率５８％）
を得、これを実施例１と同様に処理することにより、遊
離の５‐（１‐ヒドロキシ‐１‐フェニル）ヒダントイ
ン４４．７ｇ（収率７４．８％）を白色結晶として得、
更にエタノールから再結晶した。 Example 2 The amount of water charged was increased from 75 ml to 100 ml, 39.7 g (0.55 mol) of isobutyraldehyde was replaced with 58.4 g (0.55 mol) of benzaldehyde, and the oil bath temperature was changed from 110 ° C to 120 ° C. The same procedure as in Example 1 was repeated except that the temperature was increased to 5 to 5- (1-hydroxy-1-phenyl) hydantoin 1/2 barium salt 78.4 g (yield 58%).
Was obtained and treated in the same manner as in Example 1 to obtain 44.7 g (yield 74.8%) of free 5- (1-hydroxy-1-phenyl) hydantoin as white crystals.
Further, it was recrystallized from ethanol.
【００１６】質量スペクトル分析（ＦＡＢモード） 計算値（M + H + C10H11N2O3）：２０７．０７７０ 測定値 ：２０７．０７９５ 赤外線吸収スペクトル分析（KBr,cm-1） 3250, 1760, 1695, 1495, 1410, 1310,1185, 1115, 105
5, 1000, 740,695[0016] Mass spectrometry (FAB mode) calcd (M + H + C 10 H 11 N 2 O 3): 207.0770 Found: 207.0795 Infrared absorption spectrometry (KBr, cm -1) 3250, 1760 , 1695, 1495, 1410, 1310, 1185, 1115, 105
5, 1000, 740, 695
Claims (1)
１〜１０のアルキル基、低級アルキル基で置換されてい
てもよいアリール基または低級アルキル基で置換されて
いてもよいアラルキル基を表す。）で示されるアルデヒ
ドまたはケトンを、溶媒中、水酸化バリウムの存在下で
加熱することを特徴とする、一般式II 【化１】 （式中、Ｒ1 及びＲ2 は前記と同様。）で示される５‐
（ヒドロキシメチル）ヒダントイン誘導体の製造方法。1. Hydantoin and the general formula IR 1 COR 2 I (wherein R 1 and R 2 may each independently be substituted with hydrogen, an alkyl group having 1 to 10 carbon atoms or a lower alkyl group). An aldehyde or ketone represented by an aryl group or an aralkyl group which may be substituted with a lower alkyl group.) Is heated in a solvent in the presence of barium hydroxide. 1] (Wherein R 1 and R 2 are the same as above)
A method for producing a (hydroxymethyl) hydantoin derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3255368A JPH0597814A (en) | 1991-10-02 | 1991-10-02 | Method for producing 5-(hydroxymethyl) hydantoin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3255368A JPH0597814A (en) | 1991-10-02 | 1991-10-02 | Method for producing 5-(hydroxymethyl) hydantoin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0597814A true JPH0597814A (en) | 1993-04-20 |
Family
ID=17277803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3255368A Pending JPH0597814A (en) | 1991-10-02 | 1991-10-02 | Method for producing 5-(hydroxymethyl) hydantoin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0597814A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1313448C (en) * | 2001-03-15 | 2007-05-02 | 阿斯特拉泽尼卡公司 | metalloproteinase inhibitor |
-
1991
- 1991-10-02 JP JP3255368A patent/JPH0597814A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1313448C (en) * | 2001-03-15 | 2007-05-02 | 阿斯特拉泽尼卡公司 | metalloproteinase inhibitor |
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