JPH05262674A - Method for synthesizing benzyl ether of phloroglucin type phenol - Google Patents
Method for synthesizing benzyl ether of phloroglucin type phenolInfo
- Publication number
- JPH05262674A JPH05262674A JP6303592A JP6303592A JPH05262674A JP H05262674 A JPH05262674 A JP H05262674A JP 6303592 A JP6303592 A JP 6303592A JP 6303592 A JP6303592 A JP 6303592A JP H05262674 A JPH05262674 A JP H05262674A
- Authority
- JP
- Japan
- Prior art keywords
- phloroglucin
- benzyl
- type phenol
- ether
- added
- 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
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、置換フラボノイド、Ｃ
−メチル化フラボノイドやアントシアニジンなどの合成
の中間体として、有用なフロログルシン型フェノ−ルの
ベンジルエ−テルの合成法に関する。The present invention relates to a substituted flavonoid, C
-A method for synthesizing a benzyl ether of a phloroglucin-type phenol useful as an intermediate for the synthesis of methylated flavonoids and anthocyanidins.
【０００２】[0002]
【従来の技術】一般に、フェノ−ル類のベンジルエ−テ
ルの合成は、各フェノ−ルから、直接、炭酸カリウム／
ベンジルハライドの系(Journal of Organic Chemistry,
48, (1983) 1469) や、水素化ナトリウム／ベンジルハ
ライドの系(Journal of Medici-nal.Chem., 31,(1988)
2132)などでベンジル化することにより容易に行われ
る。2. Description of the Related Art Generally, the synthesis of benzyl ether of phenols is carried out directly from each phenol by using potassium carbonate /
Benzyl halide system (Journal of Organic Chemistry,
48, (1983) 1469) and sodium hydride / benzyl halide system (Journal of Medici-nal. Chem., 31, (1988)
It is easily carried out by benzylation with 2132.
【０００３】[0003]
【発明の解決しようとする課題】しかしながら、例え
ば、フロログルシンを水素化ナトリウム／ベンジルクロ
ライドの系でベンジル化すると、Ｏ−ベンジル化以外
に、Ｃ−ベンジル化が進行し、目的とするフロログルシ
ンのベンジルエ−テルは、約３０％程度の低収率にしか
得られない（Jouranal of Organic Chemistry, 41,(197
6) 3769)。However, for example, when phloroglucin is benzylated in the system of sodium hydride / benzyl chloride, C-benzylation proceeds in addition to O-benzylation, and the desired benzyl ether of phloroglucin is formed. Tell can be obtained only in a low yield of about 30% (Jouranal of Organic Chemistry, 41, (197
6) 3769).
【０００４】[0004]
【化２】 [Chemical 2]
【０００５】これは、フロログルン型フェノ−ルのフロ
ログルシン環の電子密度が高いために、通常のフェノ−
ル類とは異なった反応性を示すためと考えられる。そこ
で、本発明では、フロログルシン型フェノ−ルのベンジ
ルエ−テルを高収率で得る方法の提供を課題とした。This is because the electron density of the phloroglucin ring of the phlorogrun type phenol is high, so that it is a normal phenol.
It is considered that this is because it exhibits a different reactivity from that of the rutiles. Therefore, an object of the present invention is to provide a method for obtaining a benzyl ether of a phloroglucin-type phenol in a high yield.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、フロログ
ルシン型フェノ−ルのベンジルエ−テルを合成する方法
について鋭意検討した結果、本発明を完成するに至っ
た。Means for Solving the Problems The present inventors have conducted intensive studies on a method for synthesizing a benzyl ether of a phloroglucin type phenol, and as a result, completed the present invention.
【０００７】すなわち、本発明は、フロログルシン、カ
テキン、エピカテキンのような一般式（Ｉ）で表される
フロログルシン型フェノ−ルを、エステル誘導体に変換
し、引き続いて、それをベンジル化することを特徴とす
るフロログルシン型フェノ−ルのベンジルエ−テルの合
成法を提供するものである。That is, the present invention provides a method for converting a phloroglucin-type phenol represented by the general formula (I) such as phloroglucin, catechin and epicatechin into an ester derivative and subsequently benzylating it. The present invention provides a method for synthesizing a characteristic benzyl ether of a phloroglucin-type phenol.
【０００８】[0008]
【化３】 （ここで、Ｒ１〜Ｒ３は、同一または異なるものであっ
て、置換または未置換のアルキル基、または水素原子を
表わし、Ｒ１とＲ２、またはＲ２とＲ３は、環を形成し
ていてもよい。）[Chemical 3] (Here, R 1 to R 3 are the same or different and represent a substituted or unsubstituted alkyl group or a hydrogen atom, and R 1 and R 2 or R 2 and R 3 form a ring. You may have.)
【０００９】本発明の方法においては、まず、フロログ
ルシン型フェノ−ルの水酸基に、フロログルシン環の電
子密度を低下させるために、エステル基を導入する。エ
ステル化は、通常のエステル化法、すなわち、酸無水物
を用いる方法、酸クロライドを用いる方法などで容易に
行うことができる。In the method of the present invention, first, an ester group is introduced into the hydroxyl group of the phloroglucin-type phenol in order to reduce the electron density of the phloroglucin ring. The esterification can be easily performed by a usual esterification method, that is, a method using an acid anhydride, a method using an acid chloride, or the like.
【００１０】本発明で用いられるエステル誘導体として
は、アセテ−ト、クロロアセテ−ト、ベンゾエ−ト、ピ
バレ−ト、メトキシアセテ−ト、フェノキシアセテ−
ト、メチルカルボネ−ト、ビニルカルボネ−ト、ベンジ
ルカルボネ−ト、メチルカルバメ−ト、フェニルカルバ
メ−トなどが挙げられる。これらの中では、扱い易さ、
経済性及びベンジルエーテルの収率等から、アセテート
が最も好ましい。Examples of the ester derivative used in the present invention include acetate, chloroacetate, benzoate, pivalate, methoxyacetate and phenoxyacetate.
, Methyl carbonate, vinyl carbonate, benzyl carbonate, methyl carbamate, phenyl carbamate and the like. Among these, ease of handling,
Acetate is most preferable in terms of economy and yield of benzyl ether.
【００１１】次に、得られたエステル誘導体を、塩基性
条件下でベンジルエ−テルに変換する。ベンジル化の方
法としては、塩基性条件下で行われる公知のベンジル化
法が、いずれも使用可能である。しかしながら、特に、
精製の容易さ及び収率の点で、水素化ナトリウム／ベン
ジルハライドの系が好ましい。この系では、水あるいは
メチルアルコ−ルのごときアルコ−ルの適量の添加は、
反応を促進するので好ましい方法である。Next, the obtained ester derivative is converted into benzyl ether under basic conditions. As the benzylation method, any known benzylation method performed under basic conditions can be used. However, in particular,
The sodium hydride / benzyl halide system is preferred in terms of ease of purification and yield. In this system, the addition of water or an appropriate amount of alcohol such as methyl alcohol is
It is a preferred method because it accelerates the reaction.
【００１２】具体的に述べると、得られたエステル誘導
体を、N,N-ジメチルホルムアミド、アセトンのごとき極
性溶媒に溶解し、これに、弗化ベンジル、塩化ベンジ
ル、臭化ベンジル、ヨウ化ベンジルにようなベンジルハ
ライドと水素化ナトリウムを加え、さらに、反応混合物
に、水、メチルアルコ−ル、エチルアルコ−ルのごとき
アルコ−ルを滴下し、反応させる。反応液に抽出溶媒を
加えて、抽出、濃縮などの通常行われる分離操作を行う
ことにより、Ｃ−ベンジル化を起こすことなく、目的と
するベンジルエ−テルを高収率に得ることができる。ま
た、本発明の方法は、レゾルシノ−ル、カテコ−ル、ピ
ロガロ−ルなどの多価フェノ−ルにも応用が可能であ
る。Specifically, the obtained ester derivative is dissolved in a polar solvent such as N, N-dimethylformamide and acetone, and then dissolved in benzyl fluoride, benzyl chloride, benzyl bromide and benzyl iodide. Such a benzyl halide and sodium hydride are added, and further an alcohol such as water, methyl alcohol or ethyl alcohol is added dropwise to the reaction mixture for reaction. By adding an extraction solvent to the reaction solution and performing a usual separation operation such as extraction and concentration, the desired benzyl ether can be obtained in a high yield without causing C-benzylation. The method of the present invention can also be applied to polyvalent phenols such as resorcinol, catechol and pyrogallol.
【００１３】[0013]
【実施例】以下、実施例により本発明を更に詳細に説明
するが、本発明はこれに限定されるものではない。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
【００１４】［実施例１］フロログルシン（１）(504m
g,4mM) に無水酢酸(5ml) とピリジン(5ml) を加え、室
温で12時間反応させた。反応液から溶媒を留去し、フロ
ログルシントリアセテ−トを無色の結晶として得た。得
られたフロログルシントリアセテ−トをN,N-ジメチルホ
ルムアミド(20ml)に溶解し、これに塩化ベンジル(1.66m
l,14.4mM) と水素化ナトリウム(1.14g,28.8mM)を加え
た。そして、水（0.22ml,12mM)を滴下し、室温で２時間
反応させ、反応混合物を酢酸エチル抽出し、抽出液を飽
和食塩水で洗浄した。硫酸ナトリウムで乾燥後、溶媒を
留去し、残分をメタノ−ルから再結晶して、フロログル
シントリベンジルエ−テル（２）を無色の結晶として得
た(1.5086g,95.3% yield) 。[Example 1] Phloroglucin (1) (504 m
Acetic anhydride (5 ml) and pyridine (5 ml) were added to (g, 4 mM) and the mixture was reacted at room temperature for 12 hours. The solvent was distilled off from the reaction solution to obtain phloroglucin triacetate as colorless crystals. The obtained phloroglucin triacetate was dissolved in N, N-dimethylformamide (20 ml), and benzyl chloride (1.66 m
l, 14.4 mM) and sodium hydride (1.14 g, 28.8 mM) were added. Then, water (0.22 ml, 12 mM) was added dropwise, the mixture was reacted at room temperature for 2 hours, the reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine. After drying over sodium sulfate, the solvent was distilled off, and the residue was recrystallized from methanol to obtain phloroglucin tribenzyl ether (2) as colorless crystals (1.5086 g, 95.3% yield).
【００１５】[0015]
【化４】 [Chemical 4]
【００１６】［実施例２］フロログルシンジメチルエ−
テル（３）(617mg,4mM) に無水酢酸(2ml) とピリジン(2
ml) を加え、室温で12時間反応させた。反応液を濃縮し
て、溶媒を留去すると、フロログルシンジメチルエ−テ
ルのアセテ−トが、淡黄色の油状物質として、得られ
た。得られたアセテ−トを、N,N-ジメチルホルムアミド
(12ml)に溶解し、これに塩化ベンジル(0.57ml,4.8mM)と
水素化ナトリウム(384mg,9.6mM) を加えた。そして、水
（0.07ml,4mM) を滴下し、室温で３時間反応させ、反応
混合物を酢酸エチル抽出、飽和食塩水で洗浄、硫酸ナト
リウムで乾燥後、溶媒を留去し、褐色の油状物質を得
た。得られた油状物質をシリカゲルプレ−ト（展開液：
酢酸エチル／n-ヘキサン(1:4))で精製し、フロログルシ
ンジメチルエ−テルのモノベンジルエ−テル（４）を無
色の油状物質として得た(769mg,78.8% yield) 。[Example 2] Phloroglucin dimethyl ether
Tellurium (3) (617 mg, 4 mM) was added to acetic anhydride (2 ml) and pyridine (2
ml) was added, and the mixture was reacted at room temperature for 12 hours. The reaction solution was concentrated and the solvent was evaporated to obtain phloroglucin dimethyl ether acetate as a pale yellow oily substance. The obtained acetate was treated with N, N-dimethylformamide.
It was dissolved in (12 ml), and benzyl chloride (0.57 ml, 4.8 mM) and sodium hydride (384 mg, 9.6 mM) were added thereto. Then, water (0.07 ml, 4 mM) was added dropwise, and the mixture was reacted at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, the solvent was distilled off, and a brown oily substance was obtained. Obtained. The obtained oily substance was applied to a silica gel plate (developing solution:
Purification with ethyl acetate / n-hexane (1: 4) gave monobenzyl ether (4) of phloroglucin dimethyl ether as a colorless oily substance (769 mg, 78.8% yield).
【００１７】[0017]
【化５】 [Chemical 5]
【００１８】［実施例３］カテキン（５）(493mg,1.7m
M) に無水酢酸(5ml) とピリジン(5ml) を加え、室温で1
2時間攪拌した。反応液から溶媒を除去し、カテキンペ
ンタアセテ−トを淡黄色の油状物質として得た。得られ
たカテキンペンタアセテ−トをN,N-ジメチルホルムアミ
ド(8ml) に溶解し、これに臭化ベンジル(2.43ml,20.4m
M) と水素化ナトリウム(816mg,20.4mM)を加えた。さら
に水（0.12ml,6.8mM) を滴下し、０度で８時間半反応さ
せた。反応混合物を酢酸エチル抽出し、抽出液を飽和食
塩水で洗浄し、硫酸ナトリウムで乾燥後、溶媒を除去し
た。得られた油状物質をシリカゲルプレ−ト（展開液：
酢酸エチル／n-ヘキサン(1:2) で精製し、3-O-アセチル
-3',4',5,7- テトラ-O- ベンジルフラバン（６）を黄色
の油状物質として得た(832mg,70.7% yield) 。[Example 3] Catechin (5) (493 mg, 1.7 m)
Acetic anhydride (5 ml) and pyridine (5 ml) were added to
It was stirred for 2 hours. The solvent was removed from the reaction solution to obtain catechin pentaacetate as a pale yellow oily substance. The obtained catechin pentaacetate was dissolved in N, N-dimethylformamide (8 ml), and benzyl bromide (2.43 ml, 20.4 m
M) and sodium hydride (816 mg, 20.4 mM) were added. Further, water (0.12 ml, 6.8 mM) was added dropwise and the reaction was carried out at 0 ° C for 8 hours and a half. The reaction mixture was extracted with ethyl acetate, the extract was washed with saturated brine, dried over sodium sulfate, and the solvent was removed. The obtained oily substance was applied to a silica gel plate (developing solution:
Purified with ethyl acetate / n-hexane (1: 2), 3-O-acetyl
-3 ′, 4 ′, 5,7-Tetra-O-benzylflavan (6) was obtained as a yellow oily substance (832 mg, 70.7% yield).
【００１９】[0019]
【化６】 [Chemical 6]
【００２０】［比較例］フロログルシンン(162mg,1mM)
をN,N-ジメチルホルムアミド(2ml) に溶解し、これに塩
化ベンジル(0.4ml,3.6mM) を加えた。そして、炭酸カリ
ウム(1.24g,9mM) を加え、80度で一晩攪拌した。反応混
合物を酢酸エチルで抽出し、飽和食塩水で洗浄、硫酸ナ
トリウムで乾燥後、溶媒を留去した。得られた油状物質
をシリカゲルプレ−ト（展開液：塩化メチレン／n-ヘキ
サン＝1:1 ）で分離精製し、フロログルシントリベンジ
ルエ−テルを143.6mg(37.2% yield)得た。[Comparative Example] Phloroglucin (162 mg, 1 mM)
Was dissolved in N, N-dimethylformamide (2 ml), and benzyl chloride (0.4 ml, 3.6 mM) was added thereto. Then, potassium carbonate (1.24 g, 9 mM) was added, and the mixture was stirred at 80 ° C. overnight. The reaction mixture was extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained oily substance was separated and purified with a silica gel plate (developing solution: methylene chloride / n-hexane = 1: 1) to obtain 143.6 mg (37.2% yield) of phloroglucin tribenzyl ether.
【００２１】[0021]
【発明の効果】本発明の方法によれば、フロログルシン
型フェノ−ルのベンジルエ−テルを高収率かつ純度よく
得ることができる。According to the method of the present invention, benzyl ether of phloroglucin-type phenol can be obtained in high yield and in good purity.
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成４年５月１８日[Submission date] May 18, 1992
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】全文[Name of item to be corrected] Full text
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【書類名】 明細書[Document name] Statement
【発明の名称】 フロログルシン型フェノールのベンジ
ルエーテルの合成法Title: Method for synthesizing benzyl ether of phloroglucin type phenol
【特許請求の範囲】[Claims]
【化１】 （ここで、Ｒ１〜Ｒ３は、同一または異なるものであっ
て、置換または未置換のアルキル基、または水素原子を
表わし、Ｒ１とＲ２、またはＲ２とＲ３は、環を形成し
ていてもよい。）[Chemical 1] (Here, R 1 to R 3 are the same or different and represent a substituted or unsubstituted alkyl group or a hydrogen atom, and R 1 and R 2 or R 2 and R 3 form a ring. You may have.)
【発明の詳細な説明】Detailed Description of the Invention
【０００１】[0001]
【産業上の利用分野】本発明は、置換フラボノイド、Ｃ
−メチル化フラボノイドやアントシアニジンなどの合成
の中間体として、有用なフロログルシン型フェノ−ルの
ベンジルエ−テルの合成法に関する。The present invention relates to a substituted flavonoid, C
-A method for synthesizing a benzyl ether of a phloroglucin-type phenol useful as an intermediate for the synthesis of methylated flavonoids and anthocyanidins.
【０００２】[0002]
【従来の技術】一般に、フェノ−ル類のベンジルエ−テ
ルの合成は、各フェノ−ルから、直接、炭酸カリウム／
ベンジルハライドの系(Journal of Organic Chemistry,
48, (1983) 1469) や、水素化ナトリウム／ベンジルハ
ライドの系(Journal of Medici-nal.Chem., 31,(1988)
2132)などでベンジル化することにより容易に行われ
る。2. Description of the Related Art Generally, the synthesis of benzyl ether of phenols is carried out directly from each phenol by using potassium carbonate /
Benzyl halide system (Journal of Organic Chemistry,
48, (1983) 1469) and sodium hydride / benzyl halide system (Journal of Medici-nal. Chem., 31, (1988)
It is easily carried out by benzylation with 2132.
【０００３】[0003]
【発明の解決しようとする課題】しかしながら、例え
ば、フロログルシンを水素化ナトリウム／ベンジルクロ
ライドの系でベンジル化すると、Ｏ−ベンジル化以外
に、Ｃ−ベンジル化が進行し、目的とするフロログルシ
ンのベンジルエ−テルは、約３０％程度の低収率にしか
得られない（Jouranal of Organic Chemistry, 41,(197
6) 3769)。However, for example, when phloroglucin is benzylated with a system of sodium hydride / benzyl chloride, C-benzylation proceeds in addition to O-benzylation, and the desired benzyl ether of phloroglucin is formed. Tell can be obtained only in a low yield of about 30% (Jouranal of Organic Chemistry, 41, (197
6) 3769).
【０００４】[0004]
【化２】 [Chemical 2]
【０００５】これは、フロログルン型フェノ−ルのフロ
ログルシン環の電子密度が高いために、通常のフェノ−
ル類とは異なった反応性を示すためと考えられる。そこ
で、本発明では、フロログルシン型フェノ−ルのベンジ
ルエ−テルを高収率で得る方法の提供を課題とした。This is because the electron density of the phloroglucin ring of the phlorogrun type phenol is high, so that it is a normal phenol.
It is considered that this is because it exhibits a different reactivity from that of the rutiles. Therefore, an object of the present invention is to provide a method for obtaining a benzyl ether of a phloroglucin-type phenol in a high yield.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、フロログ
ルシン型フェノ−ルのベンジルエ−テルを合成する方法
について鋭意検討した結果、本発明を完成するに至っ
た。Means for Solving the Problems The present inventors have conducted intensive studies on a method for synthesizing a benzyl ether of a phloroglucin type phenol, and as a result, completed the present invention.
【０００７】すなわち、本発明は、フロログルシン、カ
テキン、エピカテキンのような一般式（Ｉ）で表される
フロログルシン型フェノ−ルを、エステル誘導体に変換
し、引き続いて、それをベンジル化することを特徴とす
るフロログルシン型フェノ−ルのベンジルエ−テルの合
成法を提供するものである。That is, the present invention provides a method for converting a phloroglucin-type phenol represented by the general formula (I) such as phloroglucin, catechin and epicatechin into an ester derivative and subsequently benzylating it. The present invention provides a method for synthesizing a characteristic benzyl ether of a phloroglucin-type phenol.
【０００８】[0008]
【化３】 （ここで、Ｒ１〜Ｒ３は、同一または異なるものであっ
て、置換または未置換のアルキル基、または水素原子を
表わし、Ｒ１とＲ２、またはＲ２とＲ３は、環を形成し
ていてもよい。）[Chemical 3] (Here, R 1 to R 3 are the same or different and represent a substituted or unsubstituted alkyl group or a hydrogen atom, and R 1 and R 2 or R 2 and R 3 form a ring. You may have.)
【０００９】本発明の方法においては、まず、フロログ
ルシン型フェノ−ルの水酸基に、フロログルシン環の電
子密度を低下させるために、エステル基を導入する。エ
ステル化は、通常のエステル化法、すなわち、酸無水物
を用いる方法、酸クロライドを用いる方法などで容易に
行うことができる。In the method of the present invention, first, an ester group is introduced into the hydroxyl group of the phloroglucin-type phenol in order to reduce the electron density of the phloroglucin ring. The esterification can be easily performed by a usual esterification method, that is, a method using an acid anhydride, a method using an acid chloride, or the like.
【００１０】本発明で用いられるエステル誘導体として
は、アセテ−ト、クロロアセテ−ト、ベンゾエ−ト、ピ
バレ−ト、メトキシアセテ−ト、フェノキシアセテ−
ト、メチルカルボネ−ト、ビニルカルボネ−ト、ベンジ
ルカルボネ−ト、メチルカルバメ−ト、フェニルカルバ
メ−トなどが挙げられる。これらの中では、扱い易さ、
経済性及びベンジルエーテルの収率等から、アセテート
が最も好ましい。Examples of the ester derivative used in the present invention include acetate, chloroacetate, benzoate, pivalate, methoxyacetate and phenoxyacetate.
, Methyl carbonate, vinyl carbonate, benzyl carbonate, methyl carbamate, phenyl carbamate and the like. Among these, ease of handling,
Acetate is most preferable in terms of economy and yield of benzyl ether.
【００１１】次に、得られたエステル誘導体を、塩基性
条件下でベンジルエ−テルに変換する。ベンジル化の方
法としては、塩基性条件下で行われる公知のベンジル化
法が、いずれも使用可能である。しかしながら、特に、
精製の容易さ及び収率の点で、水素化ナトリウム／ベン
ジルハライドの系が好ましい。この系では、水あるいは
メチルアルコ−ルのごときアルコ−ルの適量の添加は、
反応を促進するので好ましい方法である。Next, the obtained ester derivative is converted into benzyl ether under basic conditions. As the benzylation method, any known benzylation method performed under basic conditions can be used. However, in particular,
The sodium hydride / benzyl halide system is preferred in terms of ease of purification and yield. In this system, the addition of water or an appropriate amount of alcohol such as methyl alcohol is
It is a preferred method because it accelerates the reaction.
【００１２】具体的に述べると、得られたエステル誘導
体を、N,N-ジメチルホルムアミド、アセトンのごとき極
性溶媒に溶解し、これに、弗化ベンジル、塩化ベンジ
ル、臭化ベンジル、ヨウ化ベンジルにようなベンジルハ
ライドと水素化ナトリウムを加え、さらに、反応混合物
に、水、メチルアルコ−ル、エチルアルコ−ルのごとき
アルコ−ルを滴下し、反応させる。反応液に抽出溶媒を
加えて、抽出、濃縮などの通常行われる分離操作を行う
ことにより、Ｃ−ベンジル化を起こすことなく、目的と
するベンジルエ−テルを高収率に得ることができる。ま
た、本発明の方法は、レゾルシノ−ル、カテコ−ル、ピ
ロガロ−ルなどの多価フェノ−ルにも応用が可能であ
る。Specifically, the obtained ester derivative is dissolved in a polar solvent such as N, N-dimethylformamide and acetone, and then dissolved in benzyl fluoride, benzyl chloride, benzyl bromide and benzyl iodide. Such a benzyl halide and sodium hydride are added, and further an alcohol such as water, methyl alcohol or ethyl alcohol is added dropwise to the reaction mixture for reaction. By adding an extraction solvent to the reaction solution and performing a usual separation operation such as extraction and concentration, the desired benzyl ether can be obtained in a high yield without causing C-benzylation. The method of the present invention can also be applied to polyvalent phenols such as resorcinol, catechol and pyrogallol.
【００１３】[0013]
【実施例】以下、実施例により本発明を更に詳細に説明
するが、本発明はこれに限定されるものではない。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.
【００１４】［実施例１］以下の実施例及び比較例にお
いて、反応生成物の確認は、 1H-NMR により行った。 1
H-NMR の測定は、HITACHI R-600 FT NMR spectrometer
、あるいはVarianXL-200 FT NMR spectrometer で、テ
トラメチルシランを内部標準として測定した。フロログ
ルシン（１）(504mg,4mM) に無水酢酸(5ml) とピリジン
(5ml) を加え、室温で12時間反応させた。反応液から溶
媒を留去し、フロログルシントリアセテ−トを無色の結
晶として得た。得られたフロログルシントリアセテ−ト
をN,N-ジメチルホルムアミド(20ml)に溶解し、これに塩
化ベンジル(1.66ml,14.4mM) と水素化ナトリウム(1.14
g,28.8mM)を加えた。そして、水（0.22ml,12mM)を滴下
し、室温で２時間反応させ、反応混合物を酢酸エチル抽
出し、抽出液を飽和食塩水で洗浄した。硫酸ナトリウム
で乾燥後、溶媒を留去し、残分をメタノ−ルから再結晶
して、フロログルシントリベンジルエ−テル（２）を無
色の結晶として得た(1.5086g,95.3% yield) 。1 H-NMR データ（フロログルシントリベンジルエーテル
(2) ） 5.00(6H,s,benzyl-H) ，6.27(3H,s,phloroglucin-H) ，
7.10-7.60(15H,m,phenyl-H) ． 生成物の確認は、基本的には、ベンジル水素のピーク
（δ=5.00 付近）を確認することにより、行うことがで
きる。また、O-ベンジルと、C-ベンジルの区別は、O-ベ
ンジルのベンジル水素のピークがδ=5.00 付近、C-ベン
ジルのベンジル水素のピークがδ=4.00 付近にでること
により、区別可能である。[Example 1] In the following examples and comparative examples, the reaction products were confirmed by 1 H-NMR. 1
H-NMR measurement is performed by HITACHI R-600 FT NMR spectrometer.
Alternatively, it was measured on a Varian XL-200 FT NMR spectrometer using tetramethylsilane as an internal standard. Phloroglucin (1) (504mg, 4mM) in acetic anhydride (5ml) and pyridine
(5 ml) was added, and the mixture was reacted at room temperature for 12 hours. The solvent was distilled off from the reaction solution to obtain phloroglucin triacetate as colorless crystals. The obtained phloroglucin triacetate was dissolved in N, N-dimethylformamide (20 ml), and benzyl chloride (1.66 ml, 14.4 mM) and sodium hydride (1.14 ml) were added thereto.
g, 28.8 mM) was added. Then, water (0.22 ml, 12 mM) was added dropwise, the mixture was reacted at room temperature for 2 hours, the reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine. After drying over sodium sulfate, the solvent was distilled off, and the residue was recrystallized from methanol to obtain phloroglucin tribenzyl ether (2) as colorless crystals (1.5086 g, 95.3% yield). 1 H-NMR data (phloroglucin tribenzyl ether
(2)) 5.00 (6H, s, benzyl-H), 6.27 (3H, s, phloroglucin-H),
7.10-7.60 (15H, m, phenyl-H). Basically, the product can be confirmed by confirming the peak of benzyl hydrogen (around δ = 5.00). Also, O-benzyl and C-benzyl can be distinguished from each other by the peak of benzyl hydrogen of O-benzyl being around δ = 5.00 and the peak of benzyl hydrogen of C-benzyl being around δ = 4.00. ..
【００１５】[0015]
【化４】 [Chemical 4]
【００１６】［実施例２］フロログルシンジメチルエ−
テル（３）(617mg,4mM) に無水酢酸(2ml) とピリジン(2
ml) を加え、室温で12時間反応させた。反応液を濃縮し
て、溶媒を留去すると、フロログルシンジメチルエ−テ
ルのアセテ−トが、淡黄色の油状物質として、得られ
た。得られたアセテ−トを、N,N-ジメチルホルムアミド
(12ml)に溶解し、これに塩化ベンジル(0.57ml,4.8mM)と
水素化ナトリウム(384mg,9.6mM) を加えた。そして、水
（0.07ml,4mM) を滴下し、室温で３時間反応させ、反応
混合物を酢酸エチル抽出、飽和食塩水で洗浄、硫酸ナト
リウムで乾燥後、溶媒を留去し、褐色の油状物質を得
た。得られた油状物質をシリカゲルプレ−ト（展開液：
酢酸エチル／n-ヘキサン(1:4))で精製し、フロログルシ
ンジメチルエ−テルのモノベンジルエ−テル（４）を無
色の油状物質として得た(769mg,78.8% yield) 。1 H-NMR データ（フロログルシンジメチルエーテルモノ
ベンジルエーテル(4) ） 3.75(6H,s,methyl-H) ，5.01(2H,s,benzyl-H) ，6.10(1
H,s,phloroglucin-H)，6.17(2H,s,phloroglucin-H) ，
7.32-7.44(5H,m,phenyl-H)．[Example 2] Phloroglucin dimethyl ether
Tellurium (3) (617 mg, 4 mM) was added to acetic anhydride (2 ml) and pyridine (2
ml) was added, and the mixture was reacted at room temperature for 12 hours. The reaction solution was concentrated and the solvent was evaporated to obtain phloroglucin dimethyl ether acetate as a pale yellow oily substance. The obtained acetate was treated with N, N-dimethylformamide.
It was dissolved in (12 ml), and benzyl chloride (0.57 ml, 4.8 mM) and sodium hydride (384 mg, 9.6 mM) were added thereto. Then, water (0.07 ml, 4 mM) was added dropwise, and the mixture was reacted at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and the solvent was distilled off to give a brown oily substance. Obtained. The obtained oily substance was treated with a silica gel plate (developing solution:
Purification with ethyl acetate / n-hexane (1: 4)) gave monobenzyl ether (4) of phloroglucin dimethyl ether as a colorless oily substance (769 mg, 78.8% yield). 1 H-NMR data (phloroglucin dimethyl ether monobenzyl ether (4)) 3.75 (6H, s, methyl-H), 5.01 (2H, s, benzyl-H), 6.10 (1
H, s, phloroglucin-H), 6.17 (2H, s, phloroglucin-H),
7.32-7.44 (5H, m, phenyl-H).
【００１７】[0017]
【化５】 [Chemical 5]
【００１８】［実施例３］カテキン（５）(493mg,1.7m
M) に無水酢酸(5ml) とピリジン(5ml) を加え、室温で1
2時間攪拌した。反応液から溶媒を除去し、カテキンペ
ンタアセテ−トを淡黄色の油状物質として得た。得られ
たカテキンペンタアセテ−トをN,N-ジメチルホルムアミ
ド(8ml) に溶解し、これに臭化ベンジル(2.43ml,20.4m
M) と水素化ナトリウム(816mg,20.4mM)を加えた。さら
に水（0.12ml,6.8mM) を滴下し、０度で８時間半反応さ
せた。反応混合物を酢酸エチル抽出し、抽出液を飽和食
塩水で洗浄し、硫酸ナトリウムで乾燥後、溶媒を除去し
た。得られた油状物質をシリカゲルプレ−ト（展開液：
酢酸エチル／n-ヘキサン(1:2) で精製し、3-O-アセチル
-3',4',5,7- テトラ-O- ベンジルフラバン（６）を黄色
の油状物質として得た(832mg,70.7% yield) 。なお、3-
O-アセチル-3',4',5,7- テトラ-O- ベンジルフラバン
（６）の同定は、ナトリウムメチラートによりアセチル
基を加水分解後、行った。1 H-NMR データ（3',4',5,7-テトラ-O- ベンジルフラバ
ン(6) ） 2.61(1H,dd,j=16.5,9.0) ，3.10(1H,dd,j=16.5,5.5)
，3.97(1H,m) ，4.62(1H,d,j=8.5) ，4.99(2H,s,ben
zyl-H) ，5.02(2H,s,benzyl-H) ，5.16(4H,s,benzyl-H)
，6.20(1H,d,j=2.5)，6.27(1H,d,j=2.5)，6.95-7.01(3
H,2s)，7.20-7.60(20H,m)．[Example 3] Catechin (5) (493 mg, 1.7 m)
Acetic anhydride (5 ml) and pyridine (5 ml) were added to
It was stirred for 2 hours. The solvent was removed from the reaction solution to obtain catechin pentaacetate as a pale yellow oily substance. The obtained catechin pentaacetate was dissolved in N, N-dimethylformamide (8 ml), and benzyl bromide (2.43 ml, 20.4 m
M) and sodium hydride (816 mg, 20.4 mM) were added. Further, water (0.12 ml, 6.8 mM) was added dropwise and the reaction was carried out at 0 ° C for 8 hours and a half. The reaction mixture was extracted with ethyl acetate, the extract was washed with saturated brine, dried over sodium sulfate, and the solvent was removed. The obtained oily substance was applied to a silica gel plate (developing solution:
Purified with ethyl acetate / n-hexane (1: 2), 3-O-acetyl
-3 ′, 4 ′, 5,7-Tetra-O-benzylflavan (6) was obtained as a yellow oily substance (832 mg, 70.7% yield). In addition, 3-
The O-acetyl-3 ′, 4 ′, 5,7-tetra-O-benzylflavan (6) was identified after hydrolyzing the acetyl group with sodium methylate. 1 H-NMR data (3 ', 4', 5,7-tetra-O-benzylflavan (6)) 2.61 (1H, dd, j = 16.5,9.0), 3.10 (1H, dd, j = 16.5,5.5) )
, 3.97 (1H, m), 4.62 (1H, d, j = 8.5), 4.99 (2H, s, ben
zyl-H), 5.02 (2H, s, benzyl-H), 5.16 (4H, s, benzyl-H)
, 6.20 (1H, d, j = 2.5), 6.27 (1H, d, j = 2.5), 6.95-7.01 (3
H, 2s), 7.20-7.60 (20H, m).
【００１９】[0019]
【化６】 [Chemical 6]
【００２０】［比較例］フロログルシンン(162mg,1mM)
をN,N-ジメチルホルムアミド(2ml) に溶解し、これに塩
化ベンジル(0.4ml,3.6mM) を加えた。そして、炭酸カリ
ウム(1.24g,9mM) を加え、80度で一晩攪拌した。反応混
合物を酢酸エチルで抽出し、飽和食塩水で洗浄、硫酸ナ
トリウムで乾燥後、溶媒を留去した。得られた油状物質
をシリカゲルプレ−ト（展開液：塩化メチレン／n-ヘキ
サン＝1:1 ）で分離精製し、フロログルシントリベンジ
ルエ−テルを143.6mg(37.2% yield)得た。[Comparative Example] Phloroglucin (162 mg, 1 mM)
Was dissolved in N, N-dimethylformamide (2 ml), and benzyl chloride (0.4 ml, 3.6 mM) was added thereto. Then, potassium carbonate (1.24 g, 9 mM) was added, and the mixture was stirred at 80 ° C. overnight. The reaction mixture was extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained oily substance was separated and purified with a silica gel plate (developing solution: methylene chloride / n-hexane = 1: 1) to obtain 143.6 mg (37.2% yield) of phloroglucin tribenzyl ether.
【００２１】[0021]
【発明の効果】本発明の方法によれば、フロログルシン
型フェノ−ルのベンジルエ−テルを高収率かつ純度よく
得ることができる。According to the method of the present invention, benzyl ether of phloroglucin-type phenol can be obtained in high yield and in good purity.
【図面の簡単な説明】[Brief description of drawings]
【図１】実施例１の化合物(2) の 1H-NMR スペクトル図
である。FIG. 1 is a 1 H-NMR spectrum diagram of the compound (2) of Example 1.
【図２】実施例２の化合物(4) の 1H-NMR スペクトル図
である。2 is a 1 H-NMR spectrum diagram of the compound (4) of Example 2. FIG.
【図３】実施例１の化合物(6) の加水分解後の 1H-NMR
スペクトル図である。FIG. 3 1 H-NMR after hydrolysis of the compound (6) of Example 1
It is a spectrum figure.
【手続補正２】[Procedure Amendment 2]
【補正対象書類名】図面[Document name to be corrected] Drawing
【補正対象項目名】図１[Name of item to be corrected] Figure 1
【補正方法】追加[Correction method] Added
【補正内容】[Correction content]
【図１】 [Figure 1]
【手続補正３】[Procedure 3]
【補正対象書類名】図面[Document name to be corrected] Drawing
【補正対象項目名】図２[Name of item to be corrected] Figure 2
【補正方法】追加[Correction method] Added
【補正内容】[Correction content]
【図２】 [Fig. 2]
【手続補正４】[Procedure amendment 4]
【補正対象書類名】図面[Document name to be corrected] Drawing
【補正対象項目名】図３[Name of item to be corrected] Figure 3
【補正方法】追加[Correction method] Added
【補正内容】[Correction content]
【図３】 [Figure 3]
Claims (1)
型フェノ−ルから、エステル誘導体を経由してベンジル
化することを特徴とするフロログルシン型フェノ−ルの
ベンジルエ−テルの合成法。 【化１】 （ここで、Ｒ１〜Ｒ３は、同一または異なるものであっ
て、置換または未置換のアルキル基、または水素原子を
表わし、Ｒ１とＲ２、またはＲ２とＲ３は、環を形成し
ていてもよい。）1. A method for synthesizing a benzyl ether of a phloroglucin-type phenol, which comprises benzylating a phloroglucin-type phenol represented by the general formula (I) via an ester derivative. [Chemical 1] (Here, R 1 to R 3 are the same or different and represent a substituted or unsubstituted alkyl group or a hydrogen atom, and R 1 and R 2 or R 2 and R 3 form a ring. You may have.)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04063035A JP3097281B2 (en) | 1992-03-19 | 1992-03-19 | Synthesis of benzyl ether of phloroglucin-type phenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04063035A JP3097281B2 (en) | 1992-03-19 | 1992-03-19 | Synthesis of benzyl ether of phloroglucin-type phenol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05262674A true JPH05262674A (en) | 1993-10-12 |
| JP3097281B2 JP3097281B2 (en) | 2000-10-10 |
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| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |