JP3738325B2 - Method for producing silyl ether and alcohol by reduction of carboxylic acid - Google Patents

Description

【００１７】
図２に示す反応式（１）、（２）および（３）において、（II）はカルボン酸を表し、工業的に容易に入手可能な化合物から選ぶことができるものである。すなわち、式（１）および（２）において式（II）中、Rは既知のカルボン酸を構成するような各種の官能基または原子から選ばれ、このＲは反応に関与しない。式（II）のＲとして（したがって式（III）および（IV）のRとしても）好ましい官能基または原子の例としては、水素原子、ハロゲン原子、アミノ基、アルキル基、シクロアルキル基、アルケニル基、アルコキシ基、チオアルキル基、アルキルアミノ基、アリール基、アリールアミノ基、シロキシ基、オルガノシロキシ基、オルガノシリル基、複素環基（ピリジル基など）が挙げられる。アルキル基、アルコキシ基、チオアルキル基、アルキルアミノ基、オルガノシロキシ基、オルガノシリル基などにおける炭素数は特に限定されるものではないが、一般に炭素数１〜１８であり、枝分かれや環状構造があってもよい。
【００１８】
図２に示す反応式（３）において、（V）はアミドを表わし工業的に容易に入手可能な化合物から選ぶことができるものである。すなわち、反応式（３）において式（V）中、Ｒは既知のアミドを構成するような各種の官能基または原子から選ばれ、このＲは反応に関与しないものである。式（Ｖ）のＲとして（したがって式（VI）のＲとしても）好ましい官能基または原子の例としては、水素原子、ハロゲン原子、アミノ基、アルキル基、シクロアルキル基、アルケニル基、アルコキシ基、チオアルキル基、アルキルアミノ基、アリール基、アリールアミノ基、シロキシ基、オルガノシロキシ基、オルガノシリル基、複素環基（ピリジル基など）が挙げられる。アルキル基、アルコキシ基、チオアルキル基、アルキルアミノ基、オルガノシロキシ基、オルガノシリル基などにおける炭素数は特に限定されるものではないが、一般に炭素数１〜１８であり、枝分かれがあってもよい。また、反応式（３）における式（Ｖ）中、Ｒ₄およびＲ₅も、Ｒとともに既知のアミドを構成するような各種の官能基または官能基から選ぶことができる。Ｒ₄とＲ₅は互いに同一である場合が多いが、別異であってもよい。式（Ｖ）のＲ₄とＲ₅として（したがって、式（VI）のＲ₄とＲ₅としても）好ましい官能基または原子の例としては、水素原子、ハロゲン原子、アミノ基、アルキル基、シクロアルキル基、アルケニル基、アルコキシ基、チオアルキル基、アルキルアミノ基、アリール基、アリールアミノ基、シロキシ基、オルガノシロキシ基、オルガノシリル基、複素環基（ピリジル基など）が挙げられる。アルキル基、アルコキシ基、チオアルキル基、アルキルアミノ基、オルガノシロキシ基、オルガノシリル基などにおける炭素数は特に限定されるものではないが、一般に炭素数１〜１８であり、枝分かれや環状構造があってもよい。
【００１９】
本発明に従えば、このようなカルボン酸あるいはアミドを、特定の触媒の存在下にシランにより還元することにより、対応するシリルエーテルあるいはアミンが得られる。得られたシリルエーテルを還元後ただちに加水分解すれば、カルボン酸からアルコールが得られる。触媒は記述したような多核ルテニウム錯体である。触媒は単独でも作用を示すが、反応の速度を増加させ、生成物の収率をあげるために、本発明に従う触媒の活性化法を用いることが好ましい。
【００２０】
本発明に従う活性化法は、触媒を少量の溶媒に溶かし、シランを加えて短時間攪拌するものである。溶媒は、ジオキサンが特に優れているが、一般的にはテトラヒドロピラン、オキセパン、ジエチルエーテル等のエーテル系溶媒、ベンゼン等の炭化水素系溶媒も用いることができる。反応温度は、０℃から50℃の範囲が用いられるが、特に室温で行なうことが操作性の上でよい。活性化時間は、30分から24時間の任意の時間であるが、特に30分から1時間の時間が良好な結果が得られる。
【００２１】
【実施例】
以下に、本発明の特徴をさらに明らかにするため実施例を示すが、本発明はこれらの実施例によって限定されるものではない。
実施例１：３−フェニルプロピル−ジメチルエチルシリルエーテルの合成
三方コックを付けた２つ口の30ｍＬナス型フラスコを窒素置換した後、触媒〔（Acenaphthylene）Ｒｕ_３（ＣＯ）_７〕を6.0ｍｇ（9.3×10^−３ｍｍｏｌ）と１，４−ジオキサン0.18ｍＬ、ジメチルエチルシラン0.47ｍＬ（3.5ｍｍｏｌ）を加えた。室温で30分間攪拌して触媒を溶解させた後、ジヒドロけい皮酸135ｍｇ（0.91ｍｍｏｌ）を加えた。溶液を１時間攪拌させた後、１，４−ジオキサンおよび過剰のジメチルエチルシランを留去した。残った液体を減圧蒸留することにより、透明液体115ｍｇ（0.52ｍｍｏｌ）を得た。
この透明な液体について^１Ｈ ＮＭＲ，^１３Ｃ ＮＭＲ、^２９Ｓｉ ＮＭＲによる測定を行った。以下に結果を示す。
^１ Ｈ ＮＭＲ：ＣＤＣｌ _３ 中、内部標準ＣＨＣｌ _３
δ（ｐｐｍ）
７．１８−７．３１（ｍ，Ｐｈ，５Ｈ）
３．６２（ｔ，Ｊ＝７．９Ｈｚ，ＳｉＯＣＨ_２，２Ｈ）
２．６７（ｄｄ，Ｊ＝７．６，７．９Ｈｚ，ＰｈＣＨ_２，２Ｈ）
１．８５（ｍ，ＰｈＣＨ_２ＣＨ _２，２Ｈ）
０．９６（ｔ，Ｊ＝７．９Ｈｚ，ＳｉＣＨ_２ＣＨ _３，３Ｈ）
０．５８（ｑ，Ｊ＝７．９Ｈｚ，ＳｉＣＨ _２ＣＨ_３，２Ｈ）
０．０９（ｓ，ＳｉＣＨ_３，３Ｈ）
^１３ Ｃ ＮＭＲ：ＣＤＣｌ _３ 中、内部標準ＣＨＣｌ _３
δ（ｐｐｍ）
１４２．１（ｉｐｓｏ−Ｃ_６Ｈ_５）
１２８．４，１２８．３（ｍｅｔａ−Ｃ_６Ｈ_５，ｏｒｔｈｏ−Ｃ_６Ｈ_５）
１２５．７（ｐａｒａ−Ｃ_６Ｈ_５）
６２．０（ＳｉＯＣＨ_２）
３４．３（ＰｈＣＨ_２）
３２．１（ＰｈＣＨ_２ ＣＨ_２）
８．０（ＳｉＣＨ_２ ＣＨ_３）
６．７（ＳｉＣＨ_２ＣＨ_３）
−２．７（ＳｉＣＨ_３）
^２９ Ｓｉ ＮＭＲ：ＣＤＣｌ _３ 中、内部標準テトラメチルシラン
δ（ｐｐｍ） １８．５
以上の結果から上記透明液体は３−フェニルプロピル−ジメチルエチルシリルエーテルであることが確認された。
【００２２】
以下の実施例はカルボン酸の還元反応においては、上記の実施例１のような方法により生成するシリルエーテルを加水分解してアルコールとして精製した例である。またアミドの還元反応においては生成物のアミンを精製した例である。これらの結果を表１にまとめて示す。
【００２３】
【表１】

【００２４】
実施例２：３−フェニルプロピルアルコールの合成
三方コックを付け、攪拌子を入れた２つ口の３０ｍＬナス型フラスコを窒素置換した後、触媒〔（Ａｃｅｎａｐｈｔｈｙｌｅｎｅ）Ｒｕ_３（ＣＯ）_７〕を１６．５ｍｇ（２５．２×１０^−３ｍｍｏｌ）と１，４−ジオキサン０．４５ｍＬ、ジメチルエチルシラン０．８４ｍＬ（６．３ｍｍｏｌ）を加えた。室温で３０分間攪拌して触媒を溶解させた後、ジヒドロけい皮酸３８０ｍｇ（２．５５ｍｍｏｌ）を加えた。溶液を３０分攪拌させた後、１０％硫酸水溶液を７ｍＬ加え，三時間激しく攪拌した。生成物を塩化メチレンで抽出した後，ＮａＨＣＯ_３水溶液で中和、飽和食塩水で洗浄した。有機層のみを分離した後ＭｇＳＯ_４で脱水処理してろ過した。溶媒を減圧下留去して得られた液体を用いてヘキサン／酢酸エチルを展開溶媒としてシリカゲル充填カラムクロマトグラフィーを行うことで、３−フェニルプロピルアルコール２４８ｍｇ（１．８２ｍｍｏｌ、７２％）を精製した。これらの結果をエントリー１として表１に示す。
【００２５】
実施例３：デシルアルコールの合成
三方コックを付け、攪拌子を入れた２つ口の３０ｍＬナス型フラスコを窒素置換した後、触媒〔（Ａｃｅｎａｐｈｔｈｙｌｅｎｅ）Ｒｕ_３（ＣＯ）_７〕を６．６５ｍｇ（１０．２×１０^−３ｍｍｏｌ）と１，４−ジオキサン０．１８ｍＬ、ジメチルエチルシラン０．８０ｍＬ（６．１ｍｍｏｌ）を加えた。室温で３０分間攪拌して触媒を溶解させた後、カプリン酸１７５．７ｍｇ（１．０２ｍｍｏｌ）を加えた。溶液を６時間攪拌させた後、１０％硫酸水溶液を７ｍＬ加え，三時間激しく攪拌した。生成物を塩化メチレンで抽出した後，ＮａＨＣＯ_３水溶液で中和、飽和食塩水で洗浄した。有機層のみを分離した後ＭｇＳＯ_４で脱水処理してろ過した。溶媒を減圧下留去して得られた液体を用いてヘキサン／酢酸エチルを展開溶媒としてシリカゲル充填カラムクロマトグラフィーを行うことで、デシルアルコール１２６．８ｍｇ（０．８０ｍｍｏｌ、８０％）を精製した。これらの結果をエントリー２として表１に示す。
【００２６】
実施例４：ベンジルアルコールの合成
三方コックを付け、攪拌子を入れた２つ口の３０ｍＬナス型フラスコを窒素置換した後、触媒〔（Ａｃｅｎａｐｈｔｈｙｌｅｎｅ）Ｒｕ_３（ＣＯ）_７〕を７．０７ｍｇ（１０．９×１０^−３ｍｍｏｌ）と１，４−ジオキサン０．１８ｍＬ、ジメチルエチルシラン０．６１ｍＬ（４．６ｍｍｏｌ）を加えた。室温で３０分間攪拌して触媒を溶解させた後、安息香酸１３２．０ｍｇ（１．０８ｍｍｏｌ）を加えた。溶液を１８時間攪拌させた後、１０％硫酸水溶液を７ｍＬ加え，三時間激しく攪拌した。生成物を塩化メチレンで抽出した後，ＮａＨＣＯ_３水溶液で中和、飽和食塩水で洗浄した。有機層のみを分離した後ＭｇＳＯ_４で脱水処理してろ過した。溶媒を減圧下留去して得られた液体を用いてヘキサン／酢酸エチルを展開溶媒としてシリカゲル充填カラムクロマトグラフィーを行うことで、ベンジルアルコール５４．２ｍｇ（０．５０ｍｍｏｌ、４６％）を精製した。これらの結果をエントリー３として表１に示す。
【００２７】
実施例５：Ｎ，Ｎ−ジメチル−３−フェニルプロピルアミンの合成
三方コックを付け、攪拌子を入れた２つ口の３０ｍＬナス型フラスコを窒素置換した後、触媒〔（Ａｃｅｎａｐｈｔｈｙｌｅｎｅ）Ｒｕ_３（ＣＯ）_７〕を６．４０ｍｇ（９．８×１０^−３ｍｍｏｌ）と１，４−ジオキサン０．１８ｍＬ、ジメチルエチルシラン０．３２ｍＬ（２．４ｍｍｏｌ）を加えた。室温で３０分間攪拌して触媒を溶解させた後、Ｎ，Ｎ−ジメチル−ベンゼンプロパンアミド０．１６８ｍＬ（０．９９ｍｍｏｌ）を加えた。溶液を６時間攪拌させた後、１，４−ジオキサンおよび過剰のジメチルエチルシランを留去した。残った液体を減圧蒸留することにより、Ｎ，Ｎ−ジメチル−３−フェニルプロピルアミン１２１．０ｍｇ（０．７４ｍｍｏｌ、７５％）を精製した。これらの結果をエントリー４として表１に示す。
【００２８】
実施例６：Ｎ，Ｎ−ジエチル−ベンジルアミンの合成
三方コックを付け、攪拌子を入れた２つ口の３０ｍＬナス型フラスコを窒素置換した後、触媒〔（Ａｃｅｎａｐｈｔｈｙｌｅｎｅ）Ｒｕ_３（ＣＯ）_７〕を１１．０ｍｇ（１６．８×１０^−３ｍｍｏｌ）と１，４−ジオキサン０．３０ｍＬ、ジメチルエチルシラン０．５６ｍＬ（４．２ｍｍｏｌ）を加えた。室温で３０分間攪拌して触媒を溶解させた後、Ｎ，Ｎ−ジエチル−ベンジルアミド３２４．３ｍｇ（１．８３ｍｍｏｌ）を加えた。溶液を３０分間攪拌させた後、１，４−ジオキサンおよび過剰のジメチルエチルシランを留去した。残った液体を蒸留することによりＮ，Ｎ−ジエチル−ベンジルアミン１６６．４ｍｇ（１．００ｍｍｏｌ、５６％）を精製した。これらの結果をエントリー５として表１に示す。
【００２９】
実施例７：Ｎ，Ｎ−ジメチル−３−フェニルプロピルアミンの合成
三方コックを付け、攪拌子を入れた２つ口の３０ｍＬナス型フラスコを窒素置換した後、触媒〔（Ａｃｅｎａｐｈｔｈｙｌｅｎｅ）Ｒｕ_３（ＣＯ）_７〕を５．９１ｍｇ（９．１×１０^−３ｍｍｏｌ）と１，４−ジオキサン０．１８ｍＬ、ジメチルエチルシラン０．３０ｍＬ（２．４ｍｍｏｌ）を加えた。室温で３０分間攪拌して触媒を溶解させた後、１−ベンジル−２−ピロリジノン０．１４６ｍＬ（０．９１ｍｍｏｌ）を加えた。溶液を６時間攪拌させた後、１，４−ジオキサンおよび過剰のジメチルエチルシランを留去した。残った液体を減圧蒸留することによりＮ−ベンジルピロリジン６６．５ｍｇ（０．４１ｍｍｏｌ、４５％）を精製した。これらの結果をエントリー６として表１に示す。
【図面の簡単な説明】
【図１】本発明において触媒として用いられる多核ルテニウム錯体を例示する。
【図２】本発明に従い、シリルエーテル、一級アルコールおよびアミンが製造される反応スキームを概示する。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing silyl ethers, primary alcohols and amines, which are useful compounds widely used in pharmaceutical raw materials, solvents, catalysts, ligands and the like, using silane as a reducing agent, In particular, it relates to a method for producing silyl ethers and primary alcohols.
[0002]
[Prior art]
Conventionally, as a method for producing a primary alcohol by a reduction reaction of a carboxylic acid and a method for producing an amine by a reduction reaction of an amide, a method using a strong reducing agent such as lithium aluminum hydride or borane (for example, WRBrown, Organic Reactions 6, 470 (1941)) has been mainly used. However, in these reactions, the reducing agent used is water-free and must be handled under anhydrous conditions in an inert gas atmosphere. In addition, a large amount of aluminum or boron products that are difficult to separate are produced as a by-product, making it easy to operate and safe. Has disadvantages in terms of cost and economy.
[0003]
On the other hand, in recent years, a method for synthesizing primary alcohols from carboxylic acids and a method for synthesizing amines from amides using silanes as reducing agents that are easier to handle have been reported. However, a method for synthesizing alcohol by a carboxylic acid reduction reaction using silane as a reducing agent has not been known so far. Reactions of reducing carboxylic acids with trichlorosilane and amines have been reported (GS Li, DF Ehler, RA Benkeser, Org. Syn. 56, 83 (1977)), but the products are alkanes rather than alcohols. .
[0004]
As a method for reducing a carboxylic acid using silane as a reducing agent in the presence of a transition metal catalyst, a report by Sugawara et al. However, a high temperature of 100 ° C. is required and disilylacetal is a product, and a silyl ether which is a reduction product thereof is not obtained.
[0005]
As a method for synthesizing an amine from an amide by a reduction reaction using silanes, (1) a method using trichlorosilane in the presence of tripropylamine (RA Benkeser, GS Li, EC Mozdzen, J. Organomet. Chem. , 178, 21 (1979)), but in addition to aromatic carboxylic acids, operability such as using trichlorosilane and excess amine which generate hydrochloric acid that is unstable and easily harmful to water, There are problems with safety and versatility.
[0006]
In the presence of a transition metal catalyst, an amine can be synthesized by reducing an amide using silane as a reducing agent. (1) A method using chlorocarbonylbis (triphenylphosphine) rhodium as a catalyst (R. Kuwano, M. Takahashi , Y. Ito, Tetrahedron Lett., 39, 1017 (1998)), (2) A method using chloro (1,5-cyclooctadiene) rhodium dimer and triphenylphosphine as catalysts (Kamiya Masahiro, Michibata Masami Mami Igarashi and T. Fuchikami, Tetrahedron Lett. , 42, 1945 (2001) and JP-A-2001-122833).
[0007]
However, the hydrosilanes that can be used in the methods (1) and (2) are limited to dihydrosilane and trihydrosilane, and trialkylsilanes that are easy to handle cannot be used. In addition, the method (3) requires a high temperature of 100 ° C., and in many examples, requires a cocatalyst such as an amine or an alkyl halide, which is problematic in operability.
[0008]
[Problems to be solved by the invention]
An object of the present invention is to provide a new method capable of producing primary alcohols and amines under mild conditions at room temperature using silane as a reducing agent.
[0009]
[Means for Solving the Problems]
The present inventor recently produced a primary alcohol via silyl ether by reduction of carboxylic acid with silane as a reducing agent under the mild conditions of room temperature by using a specific catalyst, and used silane as a reducing agent. It was found that the production of an amine by reduction of the amide was achieved, and the above object was achieved.
[0010]
Thus, according to the present invention, a polynuclear ruthenium carbonyl complex in which a carbonyl group is coordinated to 2 to 4 ruthenium atoms is used as a main catalyst, and a silane having at least one hydrogen atom is used as a reducing agent. There are provided a method for producing a silyl ether from an acid, (2) a method for producing an alcohol by hydrolyzing the obtained silyl ether immediately after the reaction, and (3) a method for producing an amine from an amide.
[0011]
The polynuclear carbonyl complex particularly excellent as a catalyst used in the method of the present invention is a trinuclear ruthenium carbonyl complex coordinated with acenaphthylene or azulene represented by the above (A) or (B).
[0012]
In a preferred embodiment of the process of the present invention, the catalytic polynuclear ruthenium complex is activated with a silane having at least one hydrogen atom used as a reducing agent.
Note that in the chemical structural formulas shown in the present specification and drawings, carbon atoms and hydrogen atoms may be omitted in accordance with conventional expression methods.
[0013]
DETAILED DESCRIPTION OF THE INVENTION
An example of a polynuclear ruthenium carbonyl complex in which a carbonyl group is coordinated to 2 to 4 ruthenium atoms used as a catalyst in the present invention is shown in FIG. This polynuclear carbonyl complex produces reaction active catalyst species by the catalyst activation method according to the present invention. As will be apparent from the examples described later, this reactive catalyst species (1) produces silyl ether from carboxylic acid at room temperature, and (2) hydrolyzes the resulting silyl ether immediately after the reaction. Can produce an alcohol and (3) an amine from an amide. However, Ru ₃ (CO) ₁₂ which has been conventionally used as a polynuclear ruthenium carbonyl complex does not function as a catalyst for the above reaction at room temperature even when the same catalyst activation method is used.
[0014]
As the catalyst in the present invention, in particular, a trinuclear ruthenium carbonyl complex coordinated with acenaphthylene or azulene is particularly excellent in that the reduction reaction proceeds efficiently. The reason why such a trinuclear ruthenium carbonyl complex promotes the reduction of the catalyst is that acenaphthylene and azulene have a flexible interaction with the trinuclear ruthenium carbonyl species, so that the Ru atom is easily mutated to easily introduce the Si atom. It is thought that it becomes. The reason for generating active species by treatment with silane in a small amount of solvent is that this Si atom is introduced in advance in the absence of carboxylic acid or amide, acenaphthylene or an azulene derivative as a ligand, and a Ru-H bond. By issuing a multinuclear reactive species with Ru ₃ (CO) ₁₂ has no reaction activity at room temperature because there is no acenaphthylene or azulene that facilitates the introduction of Si atoms.
The above reduction reactions (1), (2), and (3) according to the present invention can be generally represented by the reaction scheme shown in FIG.
[0015]
In formulas (1), (2) and (3) of the reaction scheme shown in FIG. 2, (I) represents a silane which is a reducing agent, and can be appropriately selected from those conventionally known. That is, in any one of the reaction formulas (1), (2) and (3), in the formula (I), R ₁ , R ₂ and R ₃ are preferably selected from the same or different various functional groups or atoms. Examples of functional groups or atoms include hydrogen atoms, halogen atoms, amino groups, alkyl groups, cycloalkyl groups, alkoxy groups, thioalkyl groups, alkylamino groups, aryl groups, arylamino groups, vinyl groups, siloxy groups, organosiloxys. Group, organosilyl group, and heterocyclic group (such as pyridyl group). The number of carbon atoms in the alkyl group, alkoxy group, thioalkyl group, alkylamino group, organosiloxy group, organosilyl group, etc. is not particularly limited, but generally has 1 to 18 carbon atoms, and there are branches and cyclic structures. Also good. Particularly preferred as R ₁ , R ₂ and R ₃ are all those lower alkyl groups having 1 to 4 carbon atoms such as a methyl group and an ethyl group. Silanes having two silyl groups in the molecule shown below (corresponding to the case where R ₃ is an organosilyl group) can also be used for the reaction. N in the formula VII is not particularly limited, but generally 1 to 4 is preferable.
[0016]
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[0017]
In the reaction formulas (1), (2), and (3) shown in FIG. 2, (II) represents a carboxylic acid and can be selected from industrially easily available compounds. That is, in the formula (II) in the formulas (1) and (2), R is selected from various functional groups or atoms constituting a known carboxylic acid, and this R does not participate in the reaction. Examples of preferred functional groups or atoms as R in formula (II) (and hence as R in formulas (III) and (IV)) include hydrogen atoms, halogen atoms, amino groups, alkyl groups, cycloalkyl groups, alkenyl groups. An alkoxy group, a thioalkyl group, an alkylamino group, an aryl group, an arylamino group, a siloxy group, an organosiloxy group, an organosilyl group, a heterocyclic group (such as a pyridyl group). The number of carbon atoms in the alkyl group, alkoxy group, thioalkyl group, alkylamino group, organosiloxy group, organosilyl group, etc. is not particularly limited, but generally has 1 to 18 carbon atoms, and there are branches and cyclic structures. Also good.
[0018]
In reaction formula (3) shown in FIG. 2, (V) represents an amide and can be selected from compounds that are readily available industrially. That is, in the reaction formula (3), in the formula (V), R is selected from various functional groups or atoms constituting a known amide, and this R does not participate in the reaction. Examples of preferred functional groups or atoms as R in formula (V) (and therefore also as R in formula (VI)) include hydrogen atoms, halogen atoms, amino groups, alkyl groups, cycloalkyl groups, alkenyl groups, alkoxy groups, Examples thereof include a thioalkyl group, an alkylamino group, an aryl group, an arylamino group, a siloxy group, an organosiloxy group, an organosilyl group, and a heterocyclic group (such as a pyridyl group). The number of carbon atoms in the alkyl group, alkoxy group, thioalkyl group, alkylamino group, organosiloxy group, organosilyl group and the like is not particularly limited, but is generally 1 to 18 carbon atoms and may be branched. Also, in formula (V) in reaction formula (3), R ₄ and R ₅ can also be selected from various functional groups or functional groups that together with R constitute a known amide. R ₄ and R ₅ are often the same as each other, but may be different. Examples of preferred functional groups or atoms as R ₄ and R _{5 in} formula (V) (and therefore as R ₄ and R ₅ in formula (VI)) include hydrogen atoms, halogen atoms, amino groups, alkyl groups, cyclo Examples thereof include an alkyl group, an alkenyl group, an alkoxy group, a thioalkyl group, an alkylamino group, an aryl group, an arylamino group, a siloxy group, an organosiloxy group, an organosilyl group, and a heterocyclic group (such as a pyridyl group). The number of carbon atoms in the alkyl group, alkoxy group, thioalkyl group, alkylamino group, organosiloxy group, organosilyl group, etc. is not particularly limited, but generally has 1 to 18 carbon atoms, and there are branches and cyclic structures. Also good.
[0019]
According to the present invention, the corresponding silyl ether or amine is obtained by reducing such carboxylic acid or amide with silane in the presence of a specific catalyst. If the obtained silyl ether is hydrolyzed immediately after reduction, an alcohol can be obtained from the carboxylic acid. The catalyst is a polynuclear ruthenium complex as described. Although the catalyst alone works, it is preferable to use the catalyst activation method according to the present invention in order to increase the reaction rate and increase the product yield.
[0020]
In the activation method according to the present invention, the catalyst is dissolved in a small amount of solvent, silane is added, and the mixture is stirred for a short time. As the solvent, dioxane is particularly excellent, but generally, an ether solvent such as tetrahydropyran, oxepane, and diethyl ether, and a hydrocarbon solvent such as benzene can also be used. The reaction temperature is in the range of 0 ° C. to 50 ° C., but operation at room temperature is particularly preferable in terms of operability. The activation time is any time from 30 minutes to 24 hours, and particularly good results are obtained when the time is 30 minutes to 1 hour.
[0021]
【Example】
Examples are given below to further clarify the features of the present invention, but the present invention is not limited to these Examples.
Example 1: 3-phenylpropyl - after a 30mL round-bottom flask 2-neck gave a synthetic <br/> three-way cock dimethylethyl silyl ether was replaced with nitrogen, the catalyst _{[(Acenaphthylene) Ru 3 (CO)} 7 ] 6.0 mg (9.3 × 10 ⁻³ mmol), 1,4-dioxane 0.18 mL, and dimethylethylsilane 0.47 mL (3.5 mmol) were added. After stirring for 30 minutes at room temperature to dissolve the catalyst, 135 mg (0.91 mmol) of dihydrocinnamic acid was added. After stirring the solution for 1 hour, 1,4-dioxane and excess dimethylethylsilane were distilled off. The remaining liquid was distilled under reduced pressure to obtain 115 mg (0.52 mmol) of a transparent liquid.
This transparent liquid was measured by ¹ H NMR, ¹³ C NMR, and ²⁹ Si NMR. The results are shown below.
¹ H NMR: in CDCl _3, internal standard CHCl ₃
δ (ppm)
7.18-7.31 (m, Ph, 5H)
3.62 (t, J = 7.9 Hz, SiOCH ₂ , 2H)
2.67 (dd, J = 7.6, 7.9 Hz, PhCH ₂ , 2H)
_{1.85 (m, PhCH 2 C H} 2, 2H)
0.96 (t, J = 7.9Hz, SiCH 2 C H 3, 3H)
0.58 (q, J = 7.9 Hz, SiC H ₂ CH ₃ , 2H)
0.09 (s, SiCH ₃ , 3H)
¹³ C NMR: in CDCl _3, internal standard CHCl ₃
δ (ppm)
_{142.1 (ipso-C 6 H 5} )
_{128.4,128.3 (meta-C 6 H 5} , ortho-C 6 H 5)
_{125.7 (para-C 6 H 5} )
62.0 (SiOCH ₂ )
34.3 (PhCH ₂ )
32.1 (PhCH ₂ C H ₂₎
8.0 (SiCH ₂ C H ₃₎
6.7 (Si C H ₂ CH ₃ )
-2.7 (SiCH ₃ )
²⁹ Si NMR: Internal standard tetramethylsilane δ (ppm) 18.5 in CDCl ₃
From the above results, it was confirmed that the transparent liquid was 3-phenylpropyl-dimethylethylsilyl ether.
[0022]
In the following examples, in the reduction reaction of carboxylic acid, the silyl ether produced by the method as in Example 1 is hydrolyzed and purified as an alcohol. In the amide reduction reaction, the product amine is purified. These results are summarized in Table 1.
[0023]
[Table 1]

[0024]
Example 2: Synthesis of 3-phenylpropyl alcohol A two-necked 30 mL eggplant-shaped flask equipped with a three-way cock was purged with nitrogen, and then the catalyst [(Acenaphthylene) Ru ₃ (CO) ₇ 16.5 mg (25.2 × 10 ⁻³ mmol), 1,4-dioxane 0.45 mL, and dimethylethylsilane 0.84 mL (6.3 mmol) were added. After stirring for 30 minutes at room temperature to dissolve the catalyst, 380 mg (2.55 mmol) of dihydrocinnamic acid was added. The solution was allowed to stir for 30 minutes, then 7 mL of 10% aqueous sulfuric acid was added and stirred vigorously for 3 hours. The product was extracted with methylene chloride, neutralized with aqueous NaHCO ₃ solution, and washed with saturated brine. Only the organic layer was separated, dehydrated with MgSO ₄ and filtered. 248 mg (1.82 mmol, 72%) of 3-phenylpropyl alcohol was purified by performing column chromatography on silica gel using hexane / ethyl acetate as a developing solvent using the liquid obtained by distilling off the solvent under reduced pressure. . These results are shown in Table 1 as entry 1.
[0025]
Example 3: Synthesis of decyl alcohol A two-necked 30 mL eggplant type flask equipped with a three-way cock was replaced with nitrogen, and then the catalyst [(Acenaphthylene) Ru ₃ (CO) ₇ ] was replaced with 6 0.65 mg (10.2 × 10 ⁻³ mmol), 0.18 mL of 1,4-dioxane, and 0.80 mL (6.1 mmol) of dimethylethylsilane were added. After stirring at room temperature for 30 minutes to dissolve the catalyst, 175.7 mg (1.02 mmol) of capric acid was added. The solution was allowed to stir for 6 hours, then 7 mL of 10% aqueous sulfuric acid was added and stirred vigorously for 3 hours. The product was extracted with methylene chloride, neutralized with aqueous NaHCO ₃ solution, and washed with saturated brine. Only the organic layer was separated, dehydrated with MgSO ₄ and filtered. Decyl alcohol 126.8 mg (0.80 mmol, 80%) was purified by performing column chromatography on silica gel using hexane / ethyl acetate as a developing solvent using the liquid obtained by distilling off the solvent under reduced pressure. These results are shown in Table 1 as entry 2.
[0026]
Example 4: Synthesis of benzyl alcohol A two-necked 30 mL eggplant-shaped flask equipped with a three-way cock and purged with nitrogen was purged with nitrogen, and then the catalyst [(Acenaphthylene) Ru ₃ (CO) ₇ ] was added to 7 0.07 mg (10.9 × 10 ⁻³ mmol), 1,4-dioxane 0.18 mL, and dimethylethylsilane 0.61 mL (4.6 mmol) were added. After stirring for 30 minutes at room temperature to dissolve the catalyst, 132.0 mg (1.08 mmol) of benzoic acid was added. The solution was allowed to stir for 18 hours, then 7 mL of 10% aqueous sulfuric acid was added and stirred vigorously for 3 hours. The product was extracted with methylene chloride, neutralized with aqueous NaHCO ₃ solution, and washed with saturated brine. Only the organic layer was separated, dehydrated with MgSO ₄ and filtered. The liquid obtained by distilling off the solvent under reduced pressure was subjected to silica gel-filled column chromatography using hexane / ethyl acetate as a developing solvent, thereby purifying 54.2 mg (0.50 mmol, 46%) of benzyl alcohol. These results are shown in Table 1 as entry 3.
[0027]
Example 5: Synthesis of N, N-dimethyl-3-phenylpropylamine A two-necked 30 mL eggplant-shaped flask equipped with a three-way cock and purged with nitrogen was purged with nitrogen, and then a catalyst [(Acenaphthylene) Ru. ₃ (CO) ₇ ], 6.40 mg (9.8 × 10 ⁻³ mmol), 1,4-dioxane 0.18 mL, and dimethylethylsilane 0.32 mL (2.4 mmol) were added. After stirring for 30 minutes at room temperature to dissolve the catalyst, 0.168 mL (0.99 mmol) of N, N-dimethyl-benzenepropanamide was added. After stirring the solution for 6 hours, 1,4-dioxane and excess dimethylethylsilane were distilled off. The remaining liquid was distilled under reduced pressure to purify 121.0 mg (0.74 mmol, 75%) of N, N-dimethyl-3-phenylpropylamine. These results are shown in Table 1 as entry 4.
[0028]
Example 6: Synthesis of N, N-diethyl-benzylamine A two-necked 30 mL eggplant type flask equipped with a three-way cock was purged with nitrogen, and then the catalyst [(Acenaphthylene) Ru ₃ ( CO) ₇ ] was added in an amount of 11.0 mg (16.8 × 10 ⁻³ mmol), 1,4-dioxane 0.30 mL, and dimethylethylsilane 0.56 mL (4.2 mmol). After stirring for 30 minutes at room temperature to dissolve the catalyst, 324.3 mg (1.83 mmol) of N, N-diethyl-benzylamide was added. After the solution was stirred for 30 minutes, 1,4-dioxane and excess dimethylethylsilane were distilled off. The remaining liquid was distilled to purify 166.4 mg (1.00 mmol, 56%) of N, N-diethyl-benzylamine. These results are shown in Table 1 as entry 5.
[0029]
Example 7: Synthesis of N, N-dimethyl-3-phenylpropylamine A two-necked 30 mL eggplant-shaped flask equipped with a three-way cock and purged with nitrogen was purged with nitrogen, and then the catalyst [(Acenaphthylene) Ru. ₃ (CO) ₇ ], 5.91 mg (9.1 × 10 ⁻³ mmol), 1,4-dioxane 0.18 mL, and dimethylethylsilane 0.30 mL (2.4 mmol) were added. After stirring for 30 minutes at room temperature to dissolve the catalyst, 0.146 mL (0.91 mmol) of 1-benzyl-2-pyrrolidinone was added. After stirring the solution for 6 hours, 1,4-dioxane and excess dimethylethylsilane were distilled off. The remaining liquid was distilled under reduced pressure to purify 66.5 mg (0.41 mmol, 45%) of N-benzylpyrrolidine. These results are shown in Table 1 as entry 6.
[Brief description of the drawings]
FIG. 1 illustrates a polynuclear ruthenium complex used as a catalyst in the present invention.
FIG. 2 outlines a reaction scheme in which silyl ethers, primary alcohols and amines are prepared according to the present invention.

Claims (3)

A polynuclear ruthenium carbonyl complex in which a carbonyl group is coordinated to a ruthenium atom, and an acenaphthylene or azulene coordinated trinuclear ruthenium carbonyl complex represented by the following formula (A) or (B) is used as a catalyst. Using a silane having at least one hydrogen atom represented by the formula (I) as a reducing agent, a silyl ether represented by the following general formula (III) is obtained from a carboxylic acid represented by the following general formula (II). How to manufacture.

(In Formula (I) and Formula (III), R ₁ , R ₂ and R ₃ are selected from the same or different functional groups or atoms, and are a hydrogen atom, a halogen atom, an amino group, an alkyl group, or a cycloalkyl group. Represents an alkoxy group, an alkoxy group, a thioalkyl group, an alkylamino group, an aryl group, an arylamino group, a vinyl group, a siloxy group, an organosiloxy group, an organosilyl group, or a heterocyclic group, and in the formulas (II) and (III) , R is selected from functional groups or atoms constituting a known carboxylic acid, hydrogen atom, halogen atom, amino group, alkyl group, cycloalkyl group, alkenyl group, alkoxy group, thioalkyl group, alkylamino group, aryl group, An arylamino group, a siloxy group, an organosiloxy group, an organosilyl group, or a heterocyclic group is represented.)

  The method according to claim 1, comprising using as a catalyst a polynuclear ruthenium carbonyl complex activated with a silane having at least one hydrogen atom represented by the general formula (I). A method for producing a primary alcohol represented by the following general formula (IV) by hydrolyzing the silyl ether represented by the above general formula (III) obtained by the method of claim 1 or 2.

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