JPH09124621A - Optically active 1,3-oxazolidine-2-thione derivative - Google Patents
Optically active 1,3-oxazolidine-2-thione derivativeInfo
- Publication number
- JPH09124621A JPH09124621A JP28482495A JP28482495A JPH09124621A JP H09124621 A JPH09124621 A JP H09124621A JP 28482495 A JP28482495 A JP 28482495A JP 28482495 A JP28482495 A JP 28482495A JP H09124621 A JPH09124621 A JP H09124621A
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- oxazolidine
- formula
- thione
- optically active
- 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
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、不斉炭素原子を有
するカルボン酸類の光学純度決定に有用な、新規な５，
５−ジ置換−１，３−オキサゾリジン−２−チオン誘導
体に関する。TECHNICAL FIELD The present invention relates to a novel 5, useful for determining the optical purity of carboxylic acids having an asymmetric carbon atom.
It relates to 5-disubstituted-1,3-oxazolidine-2-thione derivatives.
【０００２】[0002]
【従来の技術】不斉炭素原子を有する有機化合物には、
エナンチオマー（鏡像異性体）が存在する。そして、香
料や食品添加物では両エナンチオマーによって臭いや味
が異なり、医薬品ではサリドマイドの例に如実に示され
ているように両異性体によって、薬効や毒性が大きく異
なる。また、強誘電性液晶では純粋なキラル分子構造が
求められており、純度の低下は顕著な機能の低下をもた
らすとされている。以上のような理由から医薬、農薬、
香料、食品添加物、エレクトロニクス等の産業分野で
は、光学純度の高い光学活性化合物が求められており、
同時に正確な光学純度決定法が重要となってきている。2. Description of the Related Art Organic compounds having an asymmetric carbon atom include
There are enantiomers (enantiomers). And in flavors and food additives, the odors and tastes differ depending on both enantiomers, and in pharmaceuticals, the drug efficacy and toxicity differ greatly depending on both isomers, as is clearly shown in the example of thalidomide. Further, a ferroelectric liquid crystal is required to have a pure chiral molecular structure, and a decrease in purity is said to cause a remarkable decrease in function. For the above reasons, medicines, pesticides,
In industrial fields such as fragrances, food additives, and electronics, optically active compounds with high optical purity are required,
At the same time, accurate methods for determining optical purity are becoming important.
【０００３】従来知られている光学純度決定法として
は、旋光度の測定による方法、ＮＭＲを用いる方法、ク
ロマトグラフィーによる方法等が挙げられるが、特に正
確な含量を測定する方法としてＧＬＣやＨＰＬＣを用い
るクロマトグラフィーによる方法が重要である。そし
て、例えば光学活性なカルボン酸の光学純度をクロマト
グラフィーによる方法で決定する場合、キラルな固定相
をもつＧＬＣあるいはＨＰＬＣ用カラムを用いて分析を
行う方法が知られている。Known optical purity determination methods include a method of measuring optical rotation, a method of using NMR, a method of chromatography, and the like. GLC and HPLC are particularly preferable as a method of measuring an accurate content. The chromatographic method used is important. Then, for example, when determining the optical purity of an optically active carboxylic acid by a method by chromatography, a method of performing analysis using a GLC or HPLC column having a chiral stationary phase is known.
【０００４】[0004]
【発明が解決しようとする課題】しかしながら、キラル
な固定相をもつＧＬＣあるいはＨＰＬＣ用カラムは高価
であり、また分析対象化合物の適用範囲が狭いため、多
くの種類のカラムを用意しなければならない。また、キ
ラルな固定相をもつカラムはpH等が過酷な条件での分析
には適用できず、狭い範囲の条件下で分析を行わなけれ
ばならないという欠点があった。However, GLC or HPLC columns having a chiral stationary phase are expensive, and the applicable range of the compound to be analyzed is narrow. Therefore, many types of columns must be prepared. Further, a column having a chiral stationary phase cannot be applied to analysis under severe conditions such as pH, and has a drawback that the analysis must be performed under a narrow range of conditions.
【０００５】従って、キラルな固定相をもつカラムでは
なく通常使用されるカラムを用いたカルボン酸類の光学
純度の決定法の開発が望まれていた。Therefore, it has been desired to develop a method for determining the optical purity of carboxylic acids using a commonly used column instead of a column having a chiral stationary phase.
【０００６】[0006]
【課題を解決するための手段】かかる実情において、本
発明者らはカルボン酸類の光学純度の新たな決定法を開
発すべく鋭意研究を行った結果、下記反応式に従って、
一般式（１）で表される新規な光学活性な１，３−オキ
サゾリジン−２−チオン誘導体とカルボン酸類（２）を
縮合することによりジアステレオマーとして得られるア
シル誘導体（３）が、キラルな固定相を用いたカラムで
はなく通常用いられるカラムにより分離可能であり、そ
れにより容易にカルボン酸類の光学純度を決定すること
ができることを見出し、本発明を完成した。Under such circumstances, the present inventors have conducted diligent research to develop a new method for determining the optical purity of carboxylic acids, and as a result, according to the following reaction formula,
The acyl derivative (3) obtained as a diastereomer by condensing the novel optically active 1,3-oxazolidine-2-thione derivative represented by the general formula (1) and the carboxylic acid (2) is chiral. The present inventors have completed the present invention by finding that they can be separated by a commonly used column rather than a column using a stationary phase, and thereby the optical purity of carboxylic acids can be easily determined.
【０００７】[0007]
【化２】 Embedded image
【０００８】〔式中、Ｒ1 及びＲ2 は同一又は異なっ
て、低級アルキル基、アリール基又はアラルキル基を示
し、Ｒ3 は不斉炭素原子を有する有機基を示し、Ｘはヒ
ドロキシル基又はハロゲン原子を示し、＊は不斉炭素原
子であることを示す。〕[Wherein R 1 and R 2 are the same or different and each represents a lower alkyl group, an aryl group or an aralkyl group, R 3 represents an organic group having an asymmetric carbon atom, and X represents a hydroxyl group or a halogen group. Represents an atom, and * represents an asymmetric carbon atom. ]
【０００９】すなわち本発明は、カルボン酸類の光学純
度決定のための分析用試薬として有用な、上記一般式
（１）で表される新規な光学活性５，５−ジ置換−１，
３−オキサゾリジン−２−チオン誘導体を提供するもの
である。That is, the present invention provides a novel optically active 5,5-disubstituted-1,5 represented by the above general formula (1), which is useful as an analytical reagent for determining the optical purity of carboxylic acids.
A 3-oxazolidine-2-thione derivative is provided.
【００１０】一般式（１）中、Ｒ1 及びＲ2 で表される
基のうち、低級アルキル基としては、炭素数１〜６のア
ルキル基、例えばメチル基、エチル基、プロピル基、イ
ソプロピル基、ブチル基、イソブチル基、ｓｅｃ−ブチ
ル基、ｔｅｒｔ−ブチル基等が、アリール基としては、
フェニル基、ナフチル基等が、アラルキル基としては、
フェニル−Ｃ1-5アルキル基、例えばベンジル基等が挙
げられる。Among the groups represented by R 1 and R 2 in the general formula (1), the lower alkyl group is an alkyl group having 1 to 6 carbon atoms, for example, methyl group, ethyl group, propyl group, isopropyl group. , Butyl group, isobutyl group, sec-butyl group, tert-butyl group, etc.
Phenyl group, naphthyl group, etc., as the aralkyl group,
Examples thereof include a phenyl-C 1-5 alkyl group such as a benzyl group.
【００１１】本発明化合物（１）は、例えば次の反応式
に従って、Ｌ−もしくはＤ−α−アミノ酸又はそのエス
テル（４）とグリニャール試薬（５）との反応により容
易に得られる光学活性なアミノアルコール（６）に二硫
化炭素を反応せしめることによって製造される。The compound (1) of the present invention is an optically active amino acid easily obtained by a reaction of an L- or D-α-amino acid or its ester (4) with a Grignard reagent (5), for example, according to the following reaction formula. It is produced by reacting alcohol (6) with carbon disulfide.
【００１２】[0012]
【化３】 Embedded image
【００１３】〔式中、Ｒ1、Ｒ2及び＊は前記と同じ意味
を示し、Ｘ′はハロゲン原子を示し、Ｙは水素原子又は
低級アルキル基を示す。〕[In the formula, R 1 , R 2 and * have the same meanings as described above, X'represents a halogen atom, and Y represents a hydrogen atom or a lower alkyl group. ]
【００１４】本発明化合物（１）の出発原料であるα−
アミノ酸（４）としては、Ｌ−アラニン、Ｄ−アラニ
ン、Ｌ−イソロイシン、Ｄ−イソロイシン、Ｌ−ロイシ
ン、Ｄ−ロイシン、Ｌ−フェニルアラニン、Ｄ−フェニ
ルアラニン、Ｌ−バリン、Ｄ−バリン、Ｌ−ｔ−ロイシ
ン、Ｄ−ｔ−ロイシン、Ｄ−フェニルグリシン等が挙げ
られる。また、グリニャール試薬（５）の具体例として
はメチルマグネシウムブロミド、エチルマグネシウムク
ロリド、ｎ−プロピルマグネシウムブロミド、ｎ−ブチ
ルマグネシウムクロリド、ｎ−ペンチルマグネシウムブ
ロミド、ｎ−ヘキシルマグネシウムブロミド、フェニル
マグネシウムブロミド、ベンジルマグネシウムブロミド
等が挙げられる。Α- which is a starting material of the compound (1) of the present invention
As the amino acid (4), L-alanine, D-alanine, L-isoleucine, D-isoleucine, L-leucine, D-leucine, L-phenylalanine, D-phenylalanine, L-valine, D-valine, Lt. -Leucine, Dt-leucine, D-phenylglycine and the like can be mentioned. Specific examples of the Grignard reagent (5) include methyl magnesium bromide, ethyl magnesium chloride, n-propyl magnesium bromide, n-butyl magnesium chloride, n-pentyl magnesium bromide, n-hexyl magnesium bromide, phenyl magnesium bromide, benzyl magnesium. Examples include bromide.
【００１５】光学活性なアミノアルコール（６）と二硫
化炭素の反応は、アルコール−水の混液中又はエタノー
ル、ベンゼン、塩化メチレン等の溶媒中、塩基存在下に
室温下又は加熱下に行われる。塩基としては、水酸化リ
チウム、水酸化ナトリウム、水酸化カリウム等の無機塩
基、トリメチルアミン、トリエチルアミン、トリ−ｎ−
ブチルアミン、ジメチルアニリン、ピリジン等の有機塩
基が使用できる。The reaction between the optically active amino alcohol (6) and carbon disulfide is carried out in a mixed solution of alcohol-water or in a solvent such as ethanol, benzene or methylene chloride in the presence of a base at room temperature or under heating. Examples of the base include inorganic bases such as lithium hydroxide, sodium hydroxide and potassium hydroxide, trimethylamine, triethylamine, tri-n-
Organic bases such as butylamine, dimethylaniline and pyridine can be used.
【００１６】本反応は、通常アミノアルコール（６）１
モルに対し二硫化炭素１〜３モル及び塩基１〜３モルを
使用して行われるが、特にアミノアルコール（６）１モ
ルに対し二硫化炭素２モル程度及び塩基２モル程度を使
用して行うのが好ましい。This reaction is usually carried out using amino alcohol (6) 1
It is carried out using 1 to 3 mol of carbon disulfide and 1 to 3 mol of a base, and particularly about 2 mol of carbon disulfide and 2 mol of a base to 1 mol of amino alcohol (6). Is preferred.
【００１７】また、本発明化合物（１）は、アミノアル
コール（６）１モルに対し、塩基存在下で約１モルの二
硫化炭素を反応させた後、約１モルの２−クロロ−１，
３−ジメチルイミダゾリニウムクロリドを加えて室温付
近で反応させることによっても製造することができる。The compound (1) of the present invention is prepared by reacting 1 mol of the amino alcohol (6) with about 1 mol of carbon disulfide in the presence of a base, and then reacting with about 1 mol of 2-chloro-1,
It can also be produced by adding 3-dimethylimidazolinium chloride and reacting at around room temperature.
【００１８】本発明化合物（１）を用いてカルボン酸類
の光学純度を決定するには、以下のように行えばよい。
すなわち、ピリジン、２，６−ルチジン、トリメチルア
ミン、トリエチルアミン、トリ−ｎ−ブチルアミン等の
有機塩基、水酸化リチウム、水酸化ナトリウム、炭酸ナ
トリウム、炭酸カリウム等の無機塩基あるいは水素化ナ
トリウム、水素化カリウム等の金属水素化物の存在下、
カルボン酸ハロゲニドと本発明化合物（１）とを反応せ
しめるか、ジシクロヘキシルカルボジイミド、２−クロ
ロ−１，３−ジメチルイミダゾリニウムクロリド、カル
ボニルジイミダゾール等の縮合剤の存在下、カルボン酸
と本発明化合物（１）とを反応せしめ、アシル誘導体
（３）に導いた後、生成物を単離後あるいは反応液をそ
のままＨＰＬＣやＧＬＣ分析することにより、容易にカ
ルボン酸類の光学純度を決定することができる。The optical purity of carboxylic acids can be determined using the compound (1) of the present invention as follows.
That is, organic bases such as pyridine, 2,6-lutidine, trimethylamine, triethylamine and tri-n-butylamine, inorganic bases such as lithium hydroxide, sodium hydroxide, sodium carbonate and potassium carbonate, sodium hydride and potassium hydride. In the presence of the metal hydride of
Carboxylic acid and the compound of the present invention are obtained by reacting carboxylic acid halogenide with the compound of the present invention (1) or in the presence of a condensing agent such as dicyclohexylcarbodiimide, 2-chloro-1,3-dimethylimidazolinium chloride, carbonyldiimidazole. The optical purity of the carboxylic acid can be easily determined by reacting with (1) to lead to the acyl derivative (3), and after isolating the product or by subjecting the reaction solution to HPLC or GLC analysis as it is. .
【００１９】上記分析においては、キラルな固定相をも
つカラムではなく通常実験室で繁用されているカラムを
使用することができる。例えばＨＰＬＣのカラムとして
は、ジーエルサイエンス社製 Inertsil ODS-2, メルク
社製 Lichrospher RP-18, Macherey-Nagel社製 Nucleos
il C18等が、ＧＬＣのカラムとしてはSE-30 ３％ Chrom
osorb W AW DMCS, OV-105 ２％ Gas-chrom Q, DC-550
５％ Chromosorb W AWDMCS等を挙げることができる。In the above analysis, a column commonly used in the laboratory can be used instead of a column having a chiral stationary phase. For example, the HPLC column includes GL Sciences Inertsil ODS-2, Merck Lichrospher RP-18, Macherey-Nagel Nucleos.
il C 18 etc. is SE-30 3% Chrom as a GLC column.
osorb W AW DMCS, OV-105 2% Gas-chrom Q, DC-550
5% Chromosorb W AWDMCS etc. can be mentioned.
【００２０】[0020]
【実施例】以下、実施例を挙げて本発明を更に詳細に説
明するが、本発明はこれらに限定されるものではない。EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.
【００２１】実施例１ （４Ｓ）−４−ベンジル−５，５−ジメチル−１，３−
オキサゾリジン−２−チオンの製造Example 1 (4S) -4-benzyl-5,5-dimethyl-1,3-
Production of oxazolidine-2-thione
【００２２】[0022]
【化４】 Embedded image
【００２３】エタノール４０mlと水１０mlの混液中に、
（２Ｓ）−２−アミノ−１，１−ジメチル−３−フェニ
ル−１−プロパノール２．１０ｇ（１１．７mmol）及び
水酸化カリウム１．３１ｇ（２３．４mmol）を加え、こ
の中に二硫化炭素１．７８ｇ（２３．４mmol）を滴下し
た。終了後、室温で１時間攪拌し、更に５時間加熱還流
を続けた。放冷後、反応液に水を加え塩化メチレンで抽
出し、抽出液は水洗後無水硫酸マグネシウムで乾燥し
た。次いで、減圧下溶媒を留去して得られた結晶性残渣
を酢酸エチル／ｎ−ヘキサン（１：２）の混合溶媒で再
結晶を行い、白色結晶の標記化合物を１．９４ｇ（収率
７５％）得た。In a mixed solution of 40 ml of ethanol and 10 ml of water,
2.10 g (11.7 mmol) of (2S) -2-amino-1,1-dimethyl-3-phenyl-1-propanol and 1.31 g (23.4 mmol) of potassium hydroxide were added to which carbon disulfide was added. 1.78 g (23.4 mmol) was added dropwise. After the completion, the mixture was stirred at room temperature for 1 hour and heated under reflux for another 5 hours. After cooling, water was added to the reaction solution and extracted with methylene chloride. The extract was washed with water and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure and the obtained crystalline residue was recrystallized with a mixed solvent of ethyl acetate / n-hexane (1: 2) to obtain 1.94 g of the title compound as white crystals (yield: 75 %)Obtained.
【００２４】mp 137.5〜138.0℃ ［α］D 21.7 -203.74°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：245.2(ε21600), 205.2(ε12500) IR νmax KBr cm-1：3150, 1495, 1455, 1345, 1190, 1
085, 1050, 940,760, 7201 H-NMR(CDCl3)δ：1.56(3H,s), 1.59(3H,s),2.75(1H,d
d,J=13.4 and 10.8Hz),2.90(1H,dd,J=13.4 and 4.0Hz),
3.91(1H,dd,J=10.8 and 4.0Hz), 6.91(1H,bs),7.21-7.4
3(5H,m)13 C-NMR(CDCl3)δ：21.59, 27.24, 36.19, 66.22, 90.0
1, 127.48, 128.78,129.25, 135.93, 188.27Mp 137.5-138.0 ° C. [α] D 21.7 -203.74 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 245.2 (ε21600), 205.2 (ε12500) IR ν max KBr cm −1 : 3150, 1495 , 1455, 1345, 1190, 1
085, 1050, 940,760, 720 1 H-NMR (CDCl 3 ) δ: 1.56 (3H, s), 1.59 (3H, s), 2.75 (1H, d
d, J = 13.4 and 10.8Hz), 2.90 (1H, dd, J = 13.4 and 4.0Hz),
3.91 (1H, dd, J = 10.8 and 4.0Hz), 6.91 (1H, bs), 7.21-7.4
3 (5H, m) 13 C-NMR (CDCl 3 ) δ: 21.59, 27.24, 36.19, 66.22, 90.0
1, 127.48, 128.78,129.25, 135.93, 188.27
【００２５】実施例２ （４Ｓ）−４−ベンジル−５，５−ジエチル−１，３−
オキサゾリジン−２−チオンの製造Example 2 (4S) -4-benzyl-5,5-diethyl-1,3-
Production of oxazolidine-2-thione
【００２６】[0026]
【化５】 Embedded image
【００２７】エタノール５０mlと水１０mlの混液中に、
（２Ｓ）−２−アミノ−１，１−ジエチル−３−フェニ
ル−１−プロパノール２．１７ｇ（１０．５mmol）及び
水酸化カリウム１．１７ｇ（２１．０mmol）を加え、こ
の中に二硫化炭素１．６０ｇ（２１．０mmol）を滴下し
た。終了後、室温で３０分間攪拌し、更に６．５時間加
熱還流を続けた。以下、実施例１と同様の操作を行い、
標記化合物を１．２０ｇ（収率４６％）得た。In a mixed solution of 50 ml of ethanol and 10 ml of water,
2.17 g (10.5 mmol) of (2S) -2-amino-1,1-diethyl-3-phenyl-1-propanol and 1.17 g (21.0 mmol) of potassium hydroxide were added to which carbon disulfide was added. 1.60 g (21.0 mmol) was added dropwise. After the completion, the mixture was stirred at room temperature for 30 minutes and heated under reflux for another 6.5 hours. Thereafter, the same operation as in Example 1 is performed,
1.20 g (yield 46%) of the title compound was obtained.
【００２８】mp 67.0〜70.7℃ ［α］D 21.2 -127.61°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：245.6(ε22100), 204.8(ε13500) IR νmax KBr cm-1：3140, 1495, 1440, 1285, 1200, 1
070, 1035, 885,7151 H-NMR(CDCl3)δ：1.03(3H,t,J=7.5Hz), 1.15(3H,t,J=
7.5Hz),1.80-2.08(4H,m), 2.80(1H,dd,J=12.1 and 11.1
Hz),2.92(1H,dd,J=12.1 and 3.7Hz),3.98(1H,dd,J=11.1
and 3.7Hz), 6.91(1H,bs),7.22-7.44(5H,m)13 C-NMR(CDCl3)δ：7.05, 7.36, 24.52, 28.70, 35.92,
64.00, 94.24,127.05, 128.36, 128.85, 128.92, 135.
80, 187.72Mp 67.0 to 70.7 ° C. [α] D 21.2 -127.61 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 245.6 (ε22100), 204.8 (ε13500) IR ν max KBr cm −1 : 3140, 1495 , 1440, 1285, 1200, 1
070, 1035, 885, 715 1 H-NMR (CDCl 3 ) δ: 1.03 (3H, t, J = 7.5Hz), 1.15 (3H, t, J =
7.5Hz), 1.80-2.08 (4H, m), 2.80 (1H, dd, J = 12.1 and 11.1
Hz), 2.92 (1H, dd, J = 12.1 and 3.7Hz), 3.98 (1H, dd, J = 11.1
and 3.7Hz), 6.91 (1H, bs), 7.22-7.44 (5H, m) 13 C-NMR (CDCl 3 ) δ: 7.05, 7.36, 24.52, 28.70, 35.92,
64.00, 94.24, 127.05, 128.36, 128.85, 128.92, 135.
80, 187.72
【００２９】実施例３ （４Ｓ）−４−ベンジル−５，５−ジ−ｎ−ブチル−
１，３−オキサゾリジン−２−チオンの製造Example 3 (4S) -4-benzyl-5,5-di-n-butyl-
Production of 1,3-oxazolidine-2-thione
【００３０】[0030]
【化６】 [Chemical 6]
【００３１】エタノール１００mlと水２０mlの混液中
に、（２Ｓ）−２−アミノ−１，１−ジ−ｎ−ブチル−
３−フェニル−１−プロパノール４．６５ｇ（１７．６
mmol）及び水酸化カリウム１．９８ｇ（３５．４mmol）
を加え、この中に二硫化炭素２．６９ｇ（３５．４mmo
l）を滴下した。終了後、室温で１時間攪拌し、更に
７．５時間加熱還流を続けた。以下、実施例１と同様の
操作を行い、標記化合物を２．１１ｇ（収率３９％）得
た。In a mixture of 100 ml of ethanol and 20 ml of water, (2S) -2-amino-1,1-di-n-butyl-
3-phenyl-1-propanol 4.65 g (17.6)
mmol) and 1.98 g (35.4 mmol) of potassium hydroxide
2.69g of carbon disulfide (35.4mmo
l) was added dropwise. After the completion, the mixture was stirred at room temperature for 1 hour, and heated under reflux for 7.5 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 2.11 g (yield 39%) of the title compound.
【００３２】mp 66.0〜68.0℃ ［α］D 22.9 -132.00°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：244.8(ε22000), 204.8(ε12900) IR νmax neatcm-1：3170, 1510, 1490, 1200, 1175, 7
35, 7001 H-NMR(CDCl3)δ：0.94-0.98(6H,m), 1.37-1.89(12H,
m),2.74(1H,dd,J=12.7 and 11.1Hz),3.91(1H,dd,J=11.1
and 3.3Hz), 6.68(1H,bs),7.17-7.39(5H,m)13 C-NMR(CDCl3)δ：14.30, 23.29, 23.51, 25.64, 25.8
3, 32.83, 36.81,37.21, 65.30, 94.70, 127.90, 129.2
4, 129.71, 136.70,188.59Mp 66.0 to 68.0 ° C. [α] D 22.9 -132.00 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 244.8 (ε22000), 204.8 (ε12900) IR ν max neat cm −1 : 3170, 1510 , 1490, 1200, 1175, 7
35, 700 1 H-NMR (CDCl 3 ) δ: 0.94-0.98 (6H, m), 1.37-1.89 (12H,
m), 2.74 (1H, dd, J = 12.7 and 11.1Hz), 3.91 (1H, dd, J = 11.1
and 3.3Hz), 6.68 (1H, bs), 7.17-7.39 (5H, m) 13 C-NMR (CDCl 3 ) δ: 14.30, 23.29, 23.51, 25.64, 25.8
3, 32.83, 36.81, 37.21, 65.30, 94.70, 127.90, 129.2
4, 129.71, 136.70, 188.59
【００３３】実施例４ （４Ｓ）−４−ベンジル−５，５−ジフェニル−１，３
−オキサゾリジン−２−チオンの製造Example 4 (4S) -4-benzyl-5,5-diphenyl-1,3
-Production of oxazolidine-2-thione
【００３４】[0034]
【化７】 Embedded image
【００３５】エタノール４０mlと水１０mlの混液中に、
（２Ｓ）−２−アミノ−１，１，３−トリフェニル−１
−プロパノール３．０８ｇ（１０．２mmol）及び水酸化
カリウム１．１２ｇ（２０．４mmol）を加え、この中に
二硫化炭素１．５５ｇ（２０．４mmol）を滴下した。終
了後、室温で４０分間攪拌し、更に６時間加熱還流を続
けた。以下、実施例１と同様の操作を行い、標記化合物
を２．２０ｇ（収率６３％）得た。In a mixed solution of 40 ml of ethanol and 10 ml of water,
(2S) -2-Amino-1,1,3-triphenyl-1
3.08 g (10.2 mmol) of propanol and 1.12 g (20.4 mmol) of potassium hydroxide were added, and 1.55 g (20.4 mmol) of carbon disulfide was added dropwise thereto. After the completion, the mixture was stirred at room temperature for 40 minutes, and further heated and refluxed for 6 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 2.20 g (yield 63%) of the title compound.
【００３６】mp 132.9〜134.1℃ ［α］D 22.4 -407.70°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：248.0(ε21200), 205.2(ε35400) IR νmax KBr cm-1：3190, 1495, 1445, 1200, 1160, 1
145, 970, 745,6951 H-NMR(CDCl3)δ：2.16(1H,dd,J=13.7 and 11.5Hz),2.6
0(1H,dd,J=13.7 and 3.3Hz), 6.90(1H,bs),7.05-7.49(1
5H,m)13 C-NMR(CDCl3)δ：38.96, 65.39, 95.50, 126.05, 12
6.58, 127.50,128.46, 128.74, 128.83, 128.87, 129.2
7, 136.06,138.19, 140.95, 187.89Mp 132.9-134.1 ° C. [α] D 22.4 -407.70 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 248.0 (ε21200), 205.2 (ε35400) IR ν max KBr cm −1 : 3190, 1495 , 1445, 1200, 1160, 1
145, 970, 745, 695 1 H-NMR (CDCl 3 ) δ: 2.16 (1H, dd, J = 13.7 and 11.5Hz), 2.6
0 (1H, dd, J = 13.7 and 3.3Hz), 6.90 (1H, bs), 7.05-7.49 (1
5H, m) 13 C-NMR (CDCl 3 ) δ: 38.96, 65.39, 95.50, 126.05, 12
6.58, 127.50, 128.46, 128.74, 128.83, 128.87, 129.2
7, 136.06, 138.19, 140.95, 187.89
【００３７】実施例５ （４Ｒ）−４−ベンジル−５，５−ジフェニル−１，３
−オキサゾリジン−２−チオンの製造Example 5 (4R) -4-benzyl-5,5-diphenyl-1,3
-Production of oxazolidine-2-thione
【００３８】[0038]
【化８】 Embedded image
【００３９】エタノール４０mlと水１０mlの混液中に、
（２Ｒ）−２−アミノ−１，１，３−トリフェニル−１
−プロパノール２．４０ｇ（７．９mmol）及び水酸化ナ
トリウム０．９０ｇ（１６．１mmol）を加え、この中に
二硫化炭素１．２０ｇ（１５．８mmol）を滴下した。終
了後、室温で１５分間攪拌し、更に４．７時間加熱還流
を続けた。以下実施例１と同様の操作を行い、標記化合
物を１．０２ｇ（収率３７％）得た。In a mixed solution of 40 ml of ethanol and 10 ml of water,
(2R) -2-amino-1,1,3-triphenyl-1
2.40 g (7.9 mmol) of propanol and 0.90 g (16.1 mmol) of sodium hydroxide were added, and 1.20 g (15.8 mmol) of carbon disulfide was added dropwise thereto. After the completion, the mixture was stirred at room temperature for 15 minutes, and heated under reflux for another 4.7 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 1.02 g (yield 37%) of the title compound.
【００４０】mp 133.4〜134.2℃ ［α］D 22.0 +403.66°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：248.8(ε18600), 205.6(ε31900) IR νmax KBr cm-1：3150, 1495, 1445, 1200, 1165, 9
65, 750, 6951 H-NMR(CDCl3)δ：2.11(1H,dd,J=14.0 and 11.6Hz),2.5
9(1H,dd,J=14.0 and 3.1Hz),4.77(1H,d,J=11.6 and 3.1
Hz), 6.93(1H,bs),7.04-7.46(15H,m)13 C-NMR(CDCl3)δ：38.34, 64.77, 94.86, 125.42, 12
5.95, 126.87,127.82, 128.11, 128.22, 128.23, 128.6
3, 135.41,137.57, 140.32, 187.24Mp 133.4 to 134.2 ° C. [α] D 22.0 + 403.66 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 248.8 (ε18600), 205.6 (ε31900) IR ν max KBr cm −1 : 3150, 1495 , 1445, 1200, 1165, 9
65, 750, 695 1 H-NMR (CDCl 3 ) δ: 2.11 (1H, dd, J = 14.0 and 11.6Hz), 2.5
9 (1H, dd, J = 14.0 and 3.1Hz), 4.77 (1H, d, J = 11.6 and 3.1
Hz), 6.93 (1H, bs), 7.04-7.46 (15H, m) 13 C-NMR (CDCl 3 ) δ: 38.34, 64.77, 94.86, 125.42, 12
5.95, 126.87, 127.82, 128.11, 128.22, 128.23, 128.6
3, 135.41, 137.57, 140.32, 187.24
【００４１】実施例６ （４Ｓ）−４−メチル−５，５−ジフェニル−１，３−
オキサゾリジン−２−チオンの製造Example 6 (4S) -4-methyl-5,5-diphenyl-1,3-
Production of oxazolidine-2-thione
【００４２】[0042]
【化９】 Embedded image
【００４３】エタノール４０mlと水１０mlの混液中に、
（２Ｓ）−２−アミノ−１，１−ジフェニル−１−プロ
パノール２．５０ｇ（１１．０mmol）及び水酸化カリウ
ム１．２３ｇ（２２．０mmol）を加え、この中に二硫化
炭素１．６７ｇ（２２．０mmol）を滴下した。終了後、
室温で３０分間攪拌し、更に６時間加熱還流を続けた。
以下実施例１と同様の操作を行い、標記化合物を１．９
８ｇ（収率６６％）得た。In a mixed solution of 40 ml of ethanol and 10 ml of water,
2.50 g (11.0 mmol) of (2S) -2-amino-1,1-diphenyl-1-propanol and 1.23 g (22.0 mmol) of potassium hydroxide were added to which 1.67 g of carbon disulfide ( 22.0 mmol) was added dropwise. After the end,
The mixture was stirred at room temperature for 30 minutes, and heated under reflux for another 6 hours.
Then, the same operation as in Example 1 was carried out to give the title compound (1.9).
8 g (yield 66%) was obtained.
【００４４】mp 197.5〜198.0℃ ［α］D 20.9 -194.28°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：247.2(ε20100), 205.6(ε23400) IR νmax KBr cm-1：3260, 1495, 1445, 1325, 1270, 1
165, 890, 775,750, 6951 H-NMR(CDCl3)δ：1.04(3H,d,J=7.7Hz), 4.83(1H,q,J=
7.7Hz),7.21-7.53(11H,m)13 C-NMR(CDCl3)δ：18.45, 59.86, 96.20, 128.25, 12
8.30, 128.67,128.75, 138.45, 141.26, 188.45Mp 197.5-198.0 ° C. [α] D 20.9 -194.28 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 247.2 (ε20100), 205.6 (ε23400) IR ν max KBr cm −1 : 3260, 1495 , 1445, 1325, 1270, 1
165, 890, 775,750, 695 1 H-NMR (CDCl 3 ) δ: 1.04 (3H, d, J = 7.7Hz), 4.83 (1H, q, J =
7.7Hz), 7.21-7.53 (11H, m) 13 C-NMR (CDCl 3 ) δ: 18.45, 59.86, 96.20, 128.25, 12
8.30, 128.67,128.75, 138.45, 141.26, 188.45
【００４５】実施例７ （４Ｓ）−４−イソプロピル−５，５−ジフェニル−
１，３−オキサゾリジン−２−チオンの製造Example 7 (4S) -4-isopropyl-5,5-diphenyl-
Production of 1,3-oxazolidine-2-thione
【００４６】[0046]
【化１０】 Embedded image
【００４７】エタノール５０mlと水１２．５mlの混液中
に、（２Ｓ）−２−アミノ−１，１−ジフェニル−３−
メチル−１−ブタノール４．０１ｇ（１５．７mmol）及
び水酸化カリウム１．７６ｇ（３１．４mmol）を加え、
この中に二硫化炭素２．３９ｇ（３１．４mmol）を滴下
した。終了後、室温で３０分間攪拌し、更に３時間加熱
還流を続けた。以下実施例１と同様の操作を行い、標記
化合物を４．１１ｇ（収率８８％）得た。In a mixed solution of 50 ml of ethanol and 12.5 ml of water, (2S) -2-amino-1,1-diphenyl-3-
Methyl-1-butanol 4.01 g (15.7 mmol) and potassium hydroxide 1.76 g (31.4 mmol) were added,
2.39 g (31.4 mmol) of carbon disulfide was added dropwise thereto. After the completion, the mixture was stirred at room temperature for 30 minutes and heated under reflux for another 3 hours. Then, the same operation as in Example 1 was carried out to obtain 4.11 g (yield 88%) of the title compound.
【００４８】mp 220.4〜221.3℃ ［α］D 22.7 -303.94°(ｃ＝1.00, メタノール) UV λmax MeOH nm：248.0(ε19300), 204.8(ε26000) IR νmax KBr cm-1：3150, 1500, 1445, 1265, 1165, 9
70, 900, 830, 745,6901 H-NMR(CDCl3)δ：0.69(3H,d,J=6.6Hz), 0.92(3H,d,J=
7.0Hz), 1.88(1H,m),4.50(1H,dd,J=0.9 and 4.1Hz), 7.
25-7.52(10H,m)8.40(1H,bs)13 C-NMR(CDCl3)δ：16.28, 20.95, 29.65, 69.57, 95.6
5, 125.67, 125.73,126.49, 126.55, 128.07, 128.13,
128.56, 128.63,138.05, 142.42, 187.80Mp 220.4-221.3 ° C. [α] D 22.7 -303.94 ° (c = 1.00, methanol) UV λ max MeOH nm: 248.0 (ε 19300), 204.8 (ε 26000) IR ν max KBr cm −1 : 3150, 1500, 1445, 1265, 1165, 9
70, 900, 830, 745,690 1 H-NMR (CDCl 3 ) δ: 0.69 (3H, d, J = 6.6Hz), 0.92 (3H, d, J =
7.0Hz), 1.88 (1H, m), 4.50 (1H, dd, J = 0.9 and 4.1Hz), 7.
25-7.52 (10H, m) 8.40 (1H, bs) 13 C-NMR (CDCl 3 ) δ: 16.28, 20.95, 29.65, 69.57, 95.6
5, 125.67, 125.73, 126.49, 126.55, 128.07, 128.13,
128.56, 128.63,138.05, 142.42, 187.80
【００４９】実施例８ （４Ｒ）−４−イソプロピル−５，５−ジフェニル−
１，３−オキサゾリジン−２−チオンの製造Example 8 (4R) -4-isopropyl-5,5-diphenyl-
Production of 1,3-oxazolidine-2-thione
【００５０】[0050]
【化１１】 Embedded image
【００５１】エタノール４０mlと水１０mlの混液中に、
（２Ｒ）−２−アミノ−１，１−ジフェニル−３−メチ
ル−１−ブタノール２．５０ｇ（９．８mmol）及び水酸
化カリウム１．１０ｇ（１９．６mmol）を加え、この中
に二硫化炭素１．４９ｇ（１９．６mmol）を滴下した。
終了後、室温で３０分間攪拌し、更に７時間加熱還流を
続けた。以下実施例１と同様の操作を行い、標記化合物
を２．２１ｇ（収率７６％）得た。In a mixed solution of 40 ml of ethanol and 10 ml of water,
2.50 g (9.8 mmol) of (2R) -2-amino-1,1-diphenyl-3-methyl-1-butanol and 1.10 g (19.6 mmol) of potassium hydroxide were added to which carbon disulfide was added. 1.49 g (19.6 mmol) was added dropwise.
After the completion, the mixture was stirred at room temperature for 30 minutes, and further heated and refluxed for 7 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 2.21 g (yield: 76%) of the title compound.
【００５２】mp 218.0〜220.0℃ ［α］D 23.1 +312.30°(ｃ＝1.00, メタノール) UV λmax MeOH nm：247.6(ε19900), 205.2(ε24900) IR νmax KBr cm-1：3150, 1500, 1445, 1265, 1165, 9
70, 900, 745, 6901 H-NMR(CDCl3)δ：0.70(3H,d,J=6.6Hz), 0.90(3H,d,J=
7.1Hz), 1.89(1H,m),4.47(1H,dd,J=0.9 and 4.1Hz), 7.
26-7.38(10H,m)7.49-7.53(1H,m)13 C-NMR(CDCl3)δ：17.00, 21.49, 30.33, 70.17, 96.7
8, 126.40, 127.24,128.80, 128.86, 129.28, 129.36,
138.72, 143.12,188.50Mp 218.0 to 220.0 ° C. [α] D 23.1 + 312.30 ° (c = 1.00, methanol) UV λ max MeOH nm: 247.6 (ε19900), 205.2 (ε24900) IR ν max KBr cm −1 : 3150, 1500, 1445, 1265, 1165, 9
70, 900, 745, 690 1 H-NMR (CDCl 3 ) δ: 0.70 (3H, d, J = 6.6Hz), 0.90 (3H, d, J =
7.1Hz), 1.89 (1H, m), 4.47 (1H, dd, J = 0.9 and 4.1Hz), 7.
26-7.38 (10H, m) 7.49-7.53 ( 1H, m) 13 C-NMR (CDCl 3) δ: 17.00, 21.49, 30.33, 70.17, 96.7
8, 126.40, 127.24, 128.80, 128.86, 129.28, 129.36,
138.72, 143.12, 188.50
【００５３】実施例９ （４Ｓ）−４−イソブチル−５，５−ジフェニル−１，
３−オキサゾリジン−２−チオンの製造Example 9 (4S) -4-isobutyl-5,5-diphenyl-1,
Production of 3-oxazolidine-2-thione
【００５４】[0054]
【化１２】 Embedded image
【００５５】エタノール４．３mlと水０．９mlの混液中
に、（２Ｓ）−２−アミノ−１，１−ジフェニル−４−
メチル−１−ペンタノール２５０mg（０．９mmol）及び
水酸化カリウム１００mg（１．９mmol）を加え、この中
に二硫化炭素１４１mg（１．９mmol）を滴下した。終了
後、室温で１０分間攪拌し、更に７時間加熱還流を続け
た。以下、実施例１と同様の操作を行い、標記化合物を
１６０mg（収率５５％）得た。In a mixed solution of 4.3 ml of ethanol and 0.9 ml of water, (2S) -2-amino-1,1-diphenyl-4-
250 mg (0.9 mmol) of methyl-1-pentanol and 100 mg (1.9 mmol) of potassium hydroxide were added, and 141 mg (1.9 mmol) of carbon disulfide was added dropwise thereto. After the completion, the mixture was stirred at room temperature for 10 minutes, and further heated and refluxed for 7 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 160 mg (yield 55%) of the title compound.
【００５６】mp 177.5〜178.5℃ ［α］D 22.3 -338.35°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：247.6(ε18200), 204.4(ε26400) IR νmax KBr cm-1：3170, 1495, 1165, 765, 7001 H-NMR(CDCl3)δ：0.92(3H,d,J=6.6Hz), 1.01(3H,d,J=
6.6Hz), 1.12(2H,m),1.71(1H,m), 4.67(1H,m), 7.08-7.
40(10H,m),8.26(1H,d,J=0.9Hz)13 C-NMR(CDCl3)δ：21.06, 23.73, 25.39, 41.14, 62.4
8, 95.83, 125.32,126.00, 126.69, 126.75, 128.19, 1
28.26, 128.34,128.66, 128.70, 138.38, 141.34, 187.
93Mp 177.5 to 178.5 ° C. [α] D 22.3 -338.35 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 247.6 (ε 18200), 204.4 (ε 26400) IR ν max KBr cm −1 : 3170, 1495 , 1165, 765, 700 1 H-NMR (CDCl 3 ) δ: 0.92 (3H, d, J = 6.6Hz), 1.01 (3H, d, J =
6.6Hz), 1.12 (2H, m), 1.71 (1H, m), 4.67 (1H, m), 7.08-7.
40 (10H, m), 8.26 (1H, d, J = 0.9Hz) 13 C-NMR (CDCl 3 ) δ: 21.06, 23.73, 25.39, 41.14, 62.4
8, 95.83, 125.32, 126.00, 126.69, 126.75, 128.19, 1
28.26, 128.34, 128.66, 128.70, 138.38, 141.34, 187.
93
【００５７】実施例１０ （４Ｓ）−４−ｔ−ブチル−５，５−ジフェニル−１，
３−オキサゾリジン−２−チオンの製造Example 10 (4S) -4-t-butyl-5,5-diphenyl-1,
Production of 3-oxazolidine-2-thione
【００５８】[0058]
【化１３】 Embedded image
【００５９】エタノール６０mlと水１２mlの混液中に、
（２Ｓ）−２−アミノ−３，３−ジメチル−１，１−ジ
フェニル−１−ブタノール２．００ｇ（７．４mmol）及
び水酸化カリウム０．８３ｇ（１４．９mmol）を加え、
この中に二硫化炭素１．１３ｇ（１４．９mmol）を滴下
した。終了後、室温で１時間攪拌し、更に６時間加熱還
流を続けた。以下、実施例１と同様の操作を行い、標記
化合物を０．９６ｇ（収率４１％）得た。In a mixed solution of 60 ml of ethanol and 12 ml of water,
2.00 g (7.4 mmol) of (2S) -2-amino-3,3-dimethyl-1,1-diphenyl-1-butanol and 0.83 g (14.9 mmol) of potassium hydroxide were added,
1.13 g (14.9 mmol) of carbon disulfide was added dropwise thereto. After the completion, the mixture was stirred at room temperature for 1 hour, and heated under reflux for another 6 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 0.96 g (yield 41%) of the title compound.
【００６０】mp 265.0〜267.0℃ ［α］D 21.7 -9.10°(ｃ＝0.10, メタノール) UV λmax MeOH nm：247.6(ε20200), 205.2(ε24300) IR νmax KBr cm-1：3190, 1510, 1450, 1275, 1180, 1
165, 975, 910, 745,6901 H-NMR(CDCl3)δ：0.80(9H,s), 4.40(1H,s), 7.26-7.59
(11H,m)13 C-NMR(CDCl3)δ：27.04, 45.77, 72.39, 95.92, 127.
77, 128.22, 128.34,128.60, 137.32, 143.10, 188.17Mp 265.0 to 267.0 ° C. [α] D 21.7 -9.10 ° (c = 0.10, methanol) UV λ max MeOH nm: 247.6 (ε20200), 205.2 (ε24300) IR ν max KBr cm −1 : 3190, 1510, 1450, 1275, 1180, 1
165, 975, 910, 745,690 1 H-NMR (CDCl 3 ) δ: 0.80 (9H, s), 4.40 (1H, s), 7.26-7.59
(11H, m) 13 C-NMR (CDCl 3 ) δ: 27.04, 45.77, 72.39, 95.92, 127.
77, 128.22, 128.34, 128.60, 137.32, 143.10, 188.17
【００６１】実施例１１ （４Ｒ）−４，５，５−トリフェニル−１，３−オキサ
ゾリジン−２−チオンの製造Example 11 Preparation of (4R) -4,5,5-triphenyl-1,3-oxazolidine-2-thione
【００６２】[0062]
【化１４】 Embedded image
【００６３】エタノール５０mlと水１０mlの混液中に、
（２Ｒ）−２−アミノ−１，１，２−トリフェニルエタ
ノール２．００ｇ（６．９mmol）及び水酸化カリウム
０．７８ｇ（１３．８mmol）を加え、この中に二硫化炭
素１．０５ｇ（１３．８mmol）を滴下した。終了後、室
温で３０分間攪拌し、更に７．５時間加熱還流を続け
た。以下実施例１と同様の操作を行い、標記化合物を
１．９４ｇ（収率８５％）得た。In a mixed solution of 50 ml of ethanol and 10 ml of water,
(2R) -2-Amino-1,1,2-triphenylethanol (2.00 g, 6.9 mmol) and potassium hydroxide (0.78 g, 13.8 mmol) were added, and carbon disulfide (1.05 g, 13.8 mmol) was added dropwise. After the completion, the mixture was stirred at room temperature for 30 minutes, and heated under reflux for 7.5 hours. The following procedures were performed in the same manner as in Example 1 to obtain 1.94 g (yield 85%) of the title compound.
【００６４】mp 233.2〜234.2℃ ［α］D 21.8 +223.04°(ｃ＝1.00, CHCl3) UV λmax MeOH nm：250.4(ε20500), 205.6(ε35400) IR νmax KBr cm-1：3200, 1490, 1440, 1230, 1185, 1
150, 960, 895, 820,745, 6851 H-NMR(CDCl3)δ：5.75(1H,s), 6.96-7.78(16H,m)13 C-NMR(CDCl3)δ：46.76, 111.87, 126.46, 126.50, 1
27.23, 127.30,127.61, 127.65, 127.69, 127.72, 127.
73, 128.60,128.64, 129.86, 188.23Mp 233.2-234.2 ° C. [α] D 21.8 + 223.04 ° (c = 1.00, CHCl 3 ) UV λ max MeOH nm: 250.4 (ε20500), 205.6 (ε35400) IR ν max KBr cm −1 : 3200, 1490 , 1440, 1230, 1185, 1
150, 960, 895, 820, 745, 685 1 H-NMR (CDCl 3 ) δ: 5.75 (1H, s), 6.96-7.78 (16H, m) 13 C-NMR (CDCl 3 ) δ: 46.76, 111.87, 126.46, 126.50, 1
27.23, 127.30, 127.61, 127.65, 127.69, 127.72, 127.
73, 128.60, 128.64, 129.86, 188.23
【００６５】実施例１２ （４Ｓ）−４−イソブチル−５，５−ジフェニル−１，
３−オキサゾリジン−２−チオンの製造Example 12 (4S) -4-isobutyl-5,5-diphenyl-1,
Production of 3-oxazolidine-2-thione
【００６６】[0066]
【化１５】 Embedded image
【００６７】塩化メチレン２０ml中に、（２Ｓ）−２−
アミノ−１，１−ジフェニル−４−メチル−１−ペンタ
ノール２．００ｇ（７．４mmol）、トリエチルアミン
２．５５ｇ（２５．３mmol）及び二硫化炭素０．５７ｇ
（７．４mmol）を加え、室温下１時間攪拌した。この中
に、２−クロロ−１，３−ジメチルイミダゾリニウムク
ロリド１．５１ｇ（８．９mmol）の塩化メチレン５ml溶
液を滴下し、終了後、更に１８．５時間攪拌を続けた。
反応液に水を加え、塩化メチレンで抽出し、抽出液は水
洗後無水硫酸マグネシウムで乾燥した。次いで、減圧下
溶媒を留去して得た残渣をシリカゲルクロマトグラフィ
ー（溶媒 ｎ−ヘキサン／酢酸エチル）で精製し、標記
化合物を２．２２ｇ（収率９６％）得た。In 20 ml of methylene chloride, (2S) -2-
Amino-1,1-diphenyl-4-methyl-1-pentanol 2.00 g (7.4 mmol), triethylamine 2.55 g (25.3 mmol) and carbon disulfide 0.57 g.
(7.4 mmol) was added, and the mixture was stirred at room temperature for 1 hour. To this, a solution of 2-chloro-1,3-dimethylimidazolinium chloride (1.51 g, 8.9 mmol) in methylene chloride (5 ml) was added dropwise, and after completion, stirring was continued for another 18.5 hours.
Water was added to the reaction solution and extracted with methylene chloride. The extract was washed with water and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure and the obtained residue was purified by silica gel chromatography (solvent n-hexane / ethyl acetate) to obtain 2.22 g (yield 96%) of the title compound.
【００６８】実施例１３ （４Ｓ）−４−ベンジル−５，５−ジ−ｎ−ブチル−
１，３−オキサゾリジン−２−チオンの製造Example 13 (4S) -4-benzyl-5,5-di-n-butyl-
Production of 1,3-oxazolidine-2-thione
【００６９】[0069]
【化１６】 Embedded image
【００７０】塩化メチレン５０ml中に、（２Ｓ）−２−
アミノ−１，１−ジ−ｎ−ブチル−３−フェニル−１−
プロパノール２．００ｇ（７．６mmol）、トリエチルア
ミン２．６１ｇ（２５．９mmol）及び二硫化炭素０．５
８ｇ（７．６mmol）を加え室温下１時間攪拌した。この
中に２−クロロ−１，３−ジメチルイミダゾリニウムク
ロリド１．５４ｇ（９．１mmol）の塩化メチレン１０ml
溶液を滴下し、終了後、更に１５．５時間攪拌を続け
た。以下実施例１２と同様の操作を行い、標記化合物を
１．２１ｇ（収率５２％）得た。(2S) -2-in 50 ml of methylene chloride
Amino-1,1-di-n-butyl-3-phenyl-1-
Propanol 2.00 g (7.6 mmol), triethylamine 2.61 g (25.9 mmol) and carbon disulfide 0.5
8 g (7.6 mmol) was added and the mixture was stirred at room temperature for 1 hour. 2-chloro-1,3-dimethylimidazolinium chloride (1.54 g, 9.1 mmol) in methylene chloride (10 ml)
The solution was added dropwise, and after completion, stirring was continued for another 15.5 hours. The same operation as in Example 12 was performed below to obtain 1.21 g (yield 52%) of the title compound.
【００７１】応用例１ フルルビプロフェンの光学異性体分析Application Example 1 Optical isomer analysis of flurbiprofen
【００７２】[0072]
【化１７】 Embedded image
【００７３】塩化メチレン１０ml中に、ラセミ体 ２−
（２−フルオロ−４−ビフェニル）プロピオン酸１６０
mg（０．６６mmol）、（４Ｓ）−４−ベンジル−５，５
−ジ−ｎ−ブチル−１，３−オキサゾリジン−２−チオ
ン２００mg（０．６６mmol）、ジシクロヘキシルカルボ
ジイミド１４９mg（０．７２mmol）及び４−ジメチルア
ミノピリジン８mg（０．０７mmol）を加え室温下２２．
５時間攪拌した。次いで、析出晶を濾過し、塩化メチレ
ンで洗浄した。濾洗液を合し、減圧下溶媒を留去して得
た残渣をシリカゲルクロマトグラフィー（溶媒 ｎ−ヘ
キサン／酢酸エチル）にて精製し、ジアステレオマーの
等量混合物である（４Ｓ）−３−〔２−（２−フルオロ
−４−ビフェニル）プロピオニル〕−４−ベンジル−
５，５−ジ−ｎ−ブチル−１，３−オキサゾリジン−２
−チオンを得た。 IR νmax neat cm-1：1687 この混合物を次の条件でＨＰＬＣ分析したところ、Ｓ，
Ｓ体とＳ，Ｒ体のそれぞれのピークを認めた。The racemic compound 2-in 10 ml of methylene chloride
(2-Fluoro-4-biphenyl) propionic acid 160
mg (0.66 mmol), (4S) -4-benzyl-5,5
200 mg (0.66 mmol) of di-n-butyl-1,3-oxazolidine-2-thione, 149 mg (0.72 mmol) of dicyclohexylcarbodiimide and 8 mg (0.07 mmol) of 4-dimethylaminopyridine were added at room temperature.
Stir for 5 hours. Then, the precipitated crystals were filtered and washed with methylene chloride. The filtrates were combined with each other, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel chromatography (solvent n-hexane / ethyl acetate) to obtain an equal mixture of diastereomers (4S) -3. -[2- (2-Fluoro-4-biphenyl) propionyl] -4-benzyl-
5,5-di-n-butyl-1,3-oxazolidine-2
-Thion was obtained. IR ν max neat cm -1 : 1687 When this mixture was analyzed by HPLC under the following conditions, S,
Each peak of S body and S, R body was recognized.
【００７４】 分析条件１． カラム：Inertsil ODS-2 (4.6mmID×250mmL) 移動相：CH3OH：H2O＝950：50 流 速：1.0ml/min Detector：UV 254nm 保持時間 11.3分と12.0分に２本のピークを認めた。 分析条件２． カラム：Unisil Q PH５μm (4.6mmID×250mmL) 移動相：CH3OH：H2O＝800：200 流 速：1.0ml/min Detector：UV 254nm 保持時間 16.2分と17.5分に２本のピークを認めた。Analysis conditions 1. Column: Inertsil ODS-2 (4.6mmID × 250mmL) Mobile phase: CH 3 OH: H 2 O = 950: 50 Flow rate: 1.0ml / min Detector: UV 254nm Two peaks at retention times 11.3 minutes and 12.0 minutes. Admitted. Analysis conditions 2. Column: Unisil Q PH 5 μm (4.6 mm ID × 250 mm L) Mobile phase: CH 3 OH: H 2 O = 800: 200 Flow rate: 1.0 ml / min Detector: UV 254 nm Two peaks were observed at retention times of 16.2 minutes and 17.5 minutes. It was
【００７５】応用例２ ケトプロフェンの光学異性体分析Application Example 2 Optical isomer analysis of ketoprofen
【００７６】[0076]
【化１８】 Embedded image
【００７７】塩化メチレン１０ml中に、ラセミ体 ケト
プロフェン１６７mg（０．６６mmol）、（４Ｓ）−４−
ベンジル−５，５−ジ−ｎ−ブチル−１，３−オキサゾ
リジン−２−チオン２００mg（０．６６mmol）、ジシク
ロヘキシルカルボジイミド２０３mg（０．９８mmol）及
び４−ジメチルアミノピリジン１６mg（０．１３mmol）
を加え室温で２４時間攪拌した。次いで、析出晶を濾過
し、塩化メチレンで洗浄した。濾洗液を合し、減圧下溶
媒を留去して得た残渣をシリカゲルクロマトグラフィー
（溶媒 ｎ−ヘキサン／酢酸エチル）にて精製し、ジア
ステレオマーの等量混合物である（４Ｓ）−３−〔２−
（３−ベンゾイルフェニル）プロピオニル〕−４−ベン
ジル−５，５−ジ−ｎ−ブチル−１，３−オキサゾリジ
ン−２−チオンを得た。 IR νmax neat cm-1：1686, 1655 この混合物を次の条件でＨＰＬＣ分析したところ、Ｓ，
Ｓ体とＳ，Ｒ体のそれぞれのピークを認めた。In 10 ml of methylene chloride, 167 mg (0.66 mmol) of racemic ketoprofen, (4S) -4-
Benzyl-5,5-di-n-butyl-1,3-oxazolidine-2-thione 200 mg (0.66 mmol), dicyclohexylcarbodiimide 203 mg (0.98 mmol) and 4-dimethylaminopyridine 16 mg (0.13 mmol)
Was added and the mixture was stirred at room temperature for 24 hours. Then, the precipitated crystals were filtered and washed with methylene chloride. The filtrates were combined with each other, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel chromatography (solvent n-hexane / ethyl acetate) to obtain an equal mixture of diastereomers (4S) -3. -[2-
(3-Benzoylphenyl) propionyl] -4-benzyl-5,5-di-n-butyl-1,3-oxazolidine-2-thione was obtained. IR ν max neat cm -1 : 1686, 1655 When this mixture was analyzed by HPLC under the following conditions, S,
Each peak of S body and S, R body was recognized.
【００７８】 分析条件 カラム：Inertsil ODS-2 (4.6mmID×250mmL) 移動相：CH3OH：H2O＝900：100 流 速：1.0ml/min Detector：UV 254nm 保持時間 14.7分と15.4分に２本のピークを認めた。Analysis conditions Column: Inertsil ODS-2 (4.6 mmID × 250 mmL) Mobile phase: CH 3 OH: H 2 O = 900: 100 Flow rate: 1.0 ml / min Detector: UV 254 nm Retention time 14.7 minutes and 15.4 minutes Two peaks were recognized.
【００７９】[0079]
【発明の効果】本発明化合物（１）は、カルボン酸類と
反応させることにより通常用いられるカラムで光学異性
体を分離可能なアシル誘導体に導くことができるため、
カルボン酸類の光学純度の決定に有用である。INDUSTRIAL APPLICABILITY The compound (1) of the present invention can be converted into an acyl derivative which can be separated into optical isomers by a column usually used by reacting with a carboxylic acid.
It is useful for determining the optical purity of carboxylic acids.
Claims (1)
ル基、アリール基又はアラルキル基を示し、＊は不斉炭
素原子であることを示す。〕で表される光学活性な５，
５−ジ置換−１，３−オキサゾリジン−２−チオン誘導
体。1. The following general formula (1): [In the formula, R 1 and R 2 are the same or different and each represents a lower alkyl group, an aryl group or an aralkyl group, and * represents an asymmetric carbon atom. ] The optically active 5,
5-disubstituted-1,3-oxazolidine-2-thione derivative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28482495A JPH09124621A (en) | 1995-11-01 | 1995-11-01 | Optically active 1,3-oxazolidine-2-thione derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28482495A JPH09124621A (en) | 1995-11-01 | 1995-11-01 | Optically active 1,3-oxazolidine-2-thione derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09124621A true JPH09124621A (en) | 1997-05-13 |
Family
ID=17683490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28482495A Pending JPH09124621A (en) | 1995-11-01 | 1995-11-01 | Optically active 1,3-oxazolidine-2-thione derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH09124621A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100465165C (en) * | 2004-01-19 | 2009-03-04 | 中国科学院上海有机化学研究所 | Process for synthesis of chiral oxazolidine-2-thioketone compounds |
-
1995
- 1995-11-01 JP JP28482495A patent/JPH09124621A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100465165C (en) * | 2004-01-19 | 2009-03-04 | 中国科学院上海有机化学研究所 | Process for synthesis of chiral oxazolidine-2-thioketone compounds |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Deziel et al. | Asymmetric ring closure reactions mediated by a chiral C2 symmetrical organoselenium reagent | |
| MX2007014781A (en) | A process for the dynamic resolution of (substituted) (r) - or (s) -mandelic acid. | |
| Jurgens | Asymmetric synthesis of differentially protected meso-2, 6-diaminopimelic acid | |
| Currie et al. | Chirally templated boronic acid Mannich reaction in the synthesis of optically active α-amino acids | |
| US20080312457A1 (en) | Process | |
| JPH09124621A (en) | Optically active 1,3-oxazolidine-2-thione derivative | |
| EP1008590B1 (en) | Process for preparing optically active oxazolidinone derivatives | |
| JP2503994B2 (en) | Oxazolinecarboxylic acid derivative and method for producing the same | |
| EP1554235B1 (en) | Process for synthesizing l-y-methylene glutamic acid and analogs | |
| JP2879456B2 (en) | Optically active fluoroalcohol and method for producing the same | |
| JPH09143173A (en) | Optically active 5,5-diphenyl-2-oxazolidinone derivative | |
| JP2841196B2 (en) | α-substituted α-fluorocarboxylic acid compound | |
| Martin et al. | Efficient preparation of enantiomerically pure α-aryl-α-trifluoromethylglycines via Auto Seeded Programmed Polythermic Preferential Crystallization of 5-aryl-5-trifluoromethylhydantoins | |
| Zhao et al. | Photochemical studies on exo-bicyclo [2.1. 1] hexyl and bicyclo [3.1. 0] hexyl aryl ketones: two approaches for synthesis of enantiomerically enriched cyclopentene derivatives | |
| JP2834501B2 (en) | Production method and intermediate of 3,4-epoxybutyrate | |
| JPH0228144A (en) | Production of stereospecific intermediate useful for synthesis of peptide derivative | |
| Williams | Asymmetric syntheses of unnatural amino acids and hydroxyethylene Peptide isosteres | |
| JP4030583B2 (en) | Stereoselective production of 2-substituted succinic acid derivatives | |
| CA2075776A1 (en) | Diastereomerically pure intermediates and their use in the preparation of (r)- or (s)-ketoprofen | |
| JPH1045721A (en) | Production of 1-substituted-4,5-diphenyl-2-imidazolidinone and intermediate for the same | |
| KR930004511B1 (en) | The seperation method of alpha-halo alkanoic acid optical isomers composition | |
| JP3201998B2 (en) | Method for producing (S) -benzoxazine derivative and method for racemizing (R) -benzoxazine derivative | |
| JP3875315B2 (en) | Process for producing optically active acylsulfonamides | |
| JPH10279564A (en) | Optically active guanidine derivative | |
| JP3552260B2 (en) | Optical resolution of 1-amino-2-indanols |