JP4521688B2

JP4521688B2 - Method for producing N-acylhydrazine

Info

Publication number: JP4521688B2
Application number: JP2006012214A
Authority: JP
Inventors: 修小林; 正晴杉浦; シュナイダー，ウヴェ
Original assignee: Japan Science and Technology Agency; University of Tokyo NUC; National Institute of Japan Science and Technology Agency
Current assignee: Japan Science and Technology Agency; University of Tokyo NUC; National Institute of Japan Science and Technology Agency
Priority date: 2006-01-20
Filing date: 2006-01-20
Publication date: 2010-08-11
Anticipated expiration: 2026-01-20
Also published as: JP2007191440A

Description

この発明は、Ｎ−アシルヒドラゾンへのプロパギルトリハロシラン又はアレニルトリハロシランの位置特異的付加反応による、高選択的なＮ−アシルヒドラジンの合成方法に関する。 The present invention relates to a highly selective method for synthesizing N-acylhydrazine by regiospecific addition reaction of propargyltrihalosilane or allenyltrihalosilane to N-acylhydrazone.

窒素官能基を有するアレンやアルキン、例えばアレニルメチルアミン、ホモプロパギルアミン、Ｎ−アシル−Ｎ'−アレニルメチルヒドラジン、Ｎ−アシル−Ｎ’−ホモプロパギルヒドラジンなどは有機合成上有用な合成中間体である。これらを合成するための最も効率的な手法はＣ＝Ｎ結合を有する求電子剤に対するプロパギル−金属化合物及びアレニル−金属化合物の位置選択的な付加反応による炭素−炭素結合形成反応である（非特許文献１）。しかし、プロパギル及びアレニル−金属化合物の使用にあたっては、下式（化８）に示すように、プロパギル−金属化合物とアレニル−金属化合物間の転位（非特許文献２）及び非位置選択的な付加反応が問題として残されている（非特許文献３）。

また、プロパギル及びアレニル求核剤の反応性が基質に大きく依存する点も問題である（非特許文献４）。さらに、有機金属試薬を求核剤や触媒として用いる場合は、特に大スケールの反応において、安全性や環境負荷の問題が発生しやすい。 Allenes and alkynes having a nitrogen functional group such as allenylmethylamine, homopropargylamine, N-acyl-N′-allenylmethylhydrazine, N-acyl-N′-homopropargylhydrazine are useful in organic synthesis. Synthetic intermediate. The most efficient method for synthesizing them is a carbon-carbon bond formation reaction by regioselective addition reaction of propargyl-metal compound and allenyl-metal compound to an electrophile having a C═N bond (non-patent document). Reference 1). However, in the use of propargyl and allenyl-metal compounds, rearrangement between propargyl-metal compound and allenyl-metal compound (non-patent document 2) and non-regioselective addition reaction as shown in the following formula (Formula 8) Remains as a problem (Non-Patent Document 3).

Another problem is that the reactivity of propargyl and allenyl nucleophiles largely depends on the substrate (Non-patent Document 4). Furthermore, when an organometallic reagent is used as a nucleophile or a catalyst, problems such as safety and environmental burden are likely to occur particularly in a large-scale reaction.

このような中で、これまでにＮ−アシルヒドラゾンやイミンに対する種々の触媒的アリル化反応が開発されている（非特許文献５）。一方、本発明者らは最近、下式（化９）に示すようにＮ，Ｎ−ジメチルホルムアミド（ＤＭＦ）、ヘキサメチルホスホロアミド（ＨＭＰＡ）、スルホキシド、ホスフィンオキシドのような中性のルイス塩基がアリルトリクロロシランやクロチルトリクロロシランのアルデヒド、Ｎ−アシルヒドラゾンに対する求核付加反応を促進することを報告した（非特許文献６）。これらの場合には、いかなる金属触媒も使用せずに、非イオン性のルイス塩基がルイス酸性を有するケイ素原子に配位することによりトリクロロシリル求核剤が活性化され、反応が進行する。

Under such circumstances, various catalytic allylation reactions for N-acylhydrazone and imine have been developed (Non-patent Document 5). On the other hand, as shown in the following formula (Chemical Formula 9), the present inventors have recently used neutral Lewis bases such as N, N-dimethylformamide (DMF), hexamethylphosphoramide (HMPA), sulfoxide, and phosphine oxide. Reported that nucleophilic addition reaction of allylic trichlorosilane and crotiltrichlorosilane to aldehydes and N-acylhydrazones was promoted (Non-patent Document 6). In these cases, the trichlorosilyl nucleophile is activated by the coordination of a nonionic Lewis base to a silicon atom having Lewis acidity without using any metal catalyst, and the reaction proceeds.

しかし、アルデヒドのプロパギル化やアレニル化の例はいくつか報告されているものの（非特許文献７、８）、Ｃ＝Ｎ結合へのアレニル化、プロパギル化の例は少ない。
（１）Goreらはエーテル中で１−メトキシアレニルリチウムを用いてヒドラゾンのアレニル化を行った(非特許文献９)。（２）秋山らは銅（I）とキラルBINAP錯体を触媒として用い、α−イミノエステルのエナンチオ選択的なアレニル化及びプロパギル化反応を行った（非特許文献１０）。（３）Prajapatiらは、臭化プロパギルを用いたインジウム金属によるBarbier型反応で、芳香族Ｎ−アリールイミン、Ｎ−アリールニトロン、Ｎ−フェニルヒドラゾンのプロパギル化を報告した（非特許文献１１）。しかしながら、これら全ての反応において、化学量論量以上の金属化合物が必要であり、基質一般性、選択性、収率なども十分ではない。 However, although some examples of propargylation and allenylation of aldehyde have been reported (Non-patent Documents 7 and 8), there are few examples of allenylation and propargylation to C = N bond.
(1) Gore et al. Performed allenylation of hydrazone using 1-methoxyallenyl lithium in ether (Non-patent Document 9). (2) Akiyama et al. Conducted enantioselective allenylation and propargylation of α-iminoester using copper (I) and chiral BINAP complex as catalysts (Non-patent Document 10). (3) Prajapati et al. Reported propargylation of aromatic N-arylimines, N-arylnitrones, and N-phenylhydrazones in a Barbier-type reaction with indium metal using propargyl bromide (Non-patent Document 11). However, all these reactions require a stoichiometric amount or more of a metal compound, and the substrate generality, selectivity, yield, etc. are not sufficient.

以前に本発明者らは、下式（化１０）に示すように塩化プロパギルから調製したプロパギルトリクロロシラン及びアレニルトリクロロシランをアルデヒドと反応させることにより、対応するアレニルアルコール及びホモプロパギルアルコールの合成法を報告した（非特許文献１２）。さらに最近、この反応の選択性、収率、基質一般性を改善した手法を報告した（非特許文献８）。

Previously, we reacted propargyltrichlorosilane and allenyltrichlorosilane prepared from propargyl chloride with an aldehyde as shown in the following formula (Chemical Formula 10) to give the corresponding allenyl alcohol and homopropargyl alcohol. The synthesis method of was reported. More recently, a method for improving the selectivity, yield, and generality of the reaction has been reported (Non-patent Document 8).

Chem. Rev. 1999, 99, 1069-1094Chem. Rev. 1999, 99, 1069-1094 J. Am. Chem. Soc. 2004, 126, 13326-13334J. Am. Chem. Soc. 2004, 126, 13326-13334 Synlett 2003, 1713-1715Synlett 2003, 1713-1715 J. Am. Chem. Soc. 2005, 127, 1787-1796J. Am. Chem. Soc. 2005, 127, 1787-1796 Org. Lett. 2005, 7, 2767-2770Org. Lett. 2005, 7, 2767-2770 Angew. Chem. Int. Ed. 2005, 44, 5176-5186Angew. Chem. Int. Ed. 2005, 44, 5176-5186 Adv. Synth. Catal. 2005, 347, 1219-1222Adv. Synth. Catal. 2005, 347, 1219-1222 Tetrahedron 2006, 62, 496-502Tetrahedron 2006, 62, 496-502 Tetrahedron Lett. 1999, 40, 5009-5012Tetrahedron Lett. 1999, 40, 5009-5012 Chem. Lett. 2002, 298-299Chem. Lett. 2002, 298-299 Tetrahedron Lett. 2003, 44, 6755-6757Tetrahedron Lett. 2003, 44, 6755-6757 J. Am. Chem. Soc. 1995, 117, 6392-6393J. Am. Chem. Soc. 1995, 117, 6392-6393

本発明者らは、これらの知見を元に、プロパギルトリハロシラン及びアレニルトリハロシランを用いたＣ＝Ｎ結合への選択的アレニル化及びプロパギル化反応による、アレニルメチルアミン及びホモプロパギルアミン並びにヒドラジンの新規な合成方法を提供する。 Based on these findings, the present inventors have used allenylmethylamine and homopropargylamine by selective allenylation and propargylation to C═N bonds using propargyltrihalosilane and allenyltrihalosilane. In addition, a novel method for synthesizing hydrazine is provided.

本発明者らはイミン等価体としてイミンよりも安定なＮ−アシルヒドラゾンを用いて検討を行った結果、従来よりも効率的にＮ−アシル−Ｎ'−アレニルメチルヒドラジン及びＮ−アシル−Ｎ’−ホモプロパギルヒドラジンを合成することができることを見出した。
これらの炭素−炭素結合形成反応は、プロパギルトリハロシラン、又はアレニルトリハロシランを用いて行われ、金属触媒を使用することなく、ジメチルホルムアミドなどの配位性溶媒を使用することにより収率及び選択性を向上させることができる。さらにいずれの反応においても３級アミンの添加が有効である。 As a result of studies using the N-acyl hydrazone that is more stable than imine as an imine equivalent, the present inventors have found that N-acyl-N′-allenylmethyl hydrazine and N-acyl-N′- are more efficient than before. It has been found that homopropargylhydrazine can be synthesized.
These carbon-carbon bond formation reactions are performed using propargyltrihalosilane or allenyltrihalosilane, and without using a metal catalyst, yield and yield can be obtained by using a coordinating solvent such as dimethylformamide. Selectivity can be improved. Furthermore, the addition of a tertiary amine is effective in any reaction.

即ち、本発明は、Ｎ−アシルヒドラゾンとプロパギルトリハロシラン又はアレニルトリハロシランとを反応させることから成るＮ−アシルヒドラジンの製法であり、即ち、下記一般式
化１：Ｒ^１ＨＣ＝ＮＮＨＣＯＲ^２
（式中、Ｒ^１は置換基を有していてもよい炭化水素基又は複素環基を表し、Ｒ^２は置換基を有していてもよい芳香族炭化水素を表す。）
で表されるＮ−アシルヒドラゾンと下記一般式
化２：ＣＨ≡Ｃ−ＣＨ_２−ＳｉＸ_３
（式中、Ｘはハロゲン原子を表す。）で表されるプロパギルトリハロシラン又は
化３：ＣＨ_２＝Ｃ＝ＣＨ−ＳｉＸ_３
（式中、Ｘはハロゲン原子を表す。）で表されるアレニルトリハロシランとを反応させることから成る下記一般式
化４：ＣＨ_２＝Ｃ＝ＣＨ−ＣＨＲ^１−ＮＨ−ＮＨＣＯＲ^２
又は
化５：ＣＨ≡Ｃ−ＣＨ_２−ＣＨＲ^１−ＮＨ−ＮＨＣＯＲ^２
（式中、Ｒ^１びＲ^２は上記と同様に定義される。）で表されるＮ−アシルヒドラジン（Ｎ−アシル−Ｎ'−アレニルメチルヒドラジン及びＮ−アシル−Ｎ'−ホモプロパギルヒドラジン）の製法である。

That is, the present invention is a method for producing N-acylhydrazine comprising reacting N-acylhydrazone with propargyltrihalosilane or allenyltrihalosilane, that is , the following general formula 1: R ¹ HC = NNHCOR ²
(In the formula, R ¹ represents a hydrocarbon group or a heterocyclic group which may have a substituent, and R ² represents an aromatic hydrocarbon which may have a substituent.)
N-acylhydrazone represented by the following general formula 2: CH≡C—CH ₂ —SiX ₃
(Wherein X represents a halogen atom) or propargyltrihalosilane represented by the formula: CH ₂ ═C═CH—SiX ₃
(Wherein X represents a halogen atom) The following general formula 4 consisting of reacting with an allenyltrihalosilane represented by: CH ₂ ═C═CH—CHR ¹ —NH—NHCOR ²
Or Chemical Formula 5: CH≡C—CH ₂ —CHR ¹ —NH—NHCOR ²
(Wherein R ^{1 and} R ² are defined in the same manner as described above) (N-acyl-N′-allenylmethyl hydrazine and N-acyl-N′-homopropargyl hydrazine) It is a manufacturing method.

また、本発明は、このようにして製造されたＮ−アシルヒドラジンを、更に、ヨウ化サマリウムと反応させることから成るα−アレニルアミン又はホモプロパギルアミンの製法である。このα−アレニルアミンは下式
化６：ＣＨ_２＝Ｃ＝ＣＨ−ＣＨＲ^１−ＮＨ_２
で表され、このホモプロパギルアミンは下式
化７：ＣＨ≡Ｃ−ＣＨ_２−ＣＨＲ^１−ＮＨ_２
（式中、Ｒ^１は上記と同様に定義される。）で表されることが好ましい。 The present invention is also a method for producing α-allenylamine or homopropargylamine, which comprises reacting the N-acylhydrazine thus produced with samarium iodide. This α-allenylamine has the following formula 6: CH ₂ ═C═CH—CHR ¹ —NH ₂
This homopropargylamine is represented by the following formula 7: CH≡C—CH ₂ —CHR ¹ —NH ₂
(Wherein R ¹ is defined in the same manner as described above).

本発明により、有害な金属触媒の代わりにジメチルホルムアミドや３級アミンなどの有機化合物のみを用いることで、Ｎ−アシルヒドラゾンから、基質に特に依存せずに、高収率かつ高立体特異的にＮ−アシル−Ｎ'−アレニルメチルヒドラジン及びＮ−アシル−Ｎ’−ホモプロパギルヒドラジン誘導体を得ることが可能となった。 According to the present invention, by using only an organic compound such as dimethylformamide or tertiary amine in place of a harmful metal catalyst, N-acylhydrazone can be used in a high yield and high stereospecificity without depending on the substrate. It became possible to obtain N-acyl-N'-allenylmethylhydrazine and N-acyl-N'-homopropargylhydrazine derivatives.

本願発明の製法においては、Ｎ−アシルヒドラゾンとプロパギルトリハロシラン又はアレニルトリハロシランとを反応させることにより、Ｎ−アシルヒドラジンを合成する。
本発明で用いるＮ−アシルヒドラゾンは下記一般式（化１）で表される。
化１：Ｒ^１ＨＣ＝ＮＮＨＣＯＲ^２
本願発明の反応は一方の基質が上記Ｎ−アシルヒドラゾン構造を有していればよく、Ｒ^１及びＲ^２には特に制限はないが、Ｒ^１は置換基を有していてもよい炭化水素基又は複素環基を表し、Ｒ^２は置換基を有していてもよい芳香族炭化水素を表す。
このＲ^１の炭化水素基としては、例えば、アルキル基、アルケニル基、アリール基、アラルキル基、アルキニル基などが挙げられる。複素環基としては、例えば、チエニル基、フリル基、ピロリル基、イミダゾリル基、イソチアゾリル基、ピリジル基、インドリル基、キノリル基、イソキノリル基等が挙げられる。
これらが有していてもよい置換基としては、ハロゲン原子、短鎖アルキル基、アルコキシ基、ニトロ基、エステル基等が挙げられる。 In the production method of the present invention, N-acylhydrazine is synthesized by reacting N-acylhydrazone with propargyltrihalosilane or allenyltrihalosilane.
The N-acylhydrazone used in the present invention is represented by the following general formula (Formula 1).
Formula 1: R ¹ HC = NNHCOR ²
In the reaction of the present invention, it is sufficient that one substrate has the above-mentioned N-acylhydrazone structure, and R ¹ and R ² are not particularly limited, but R ¹ may have a substituent. Represents a group or a heterocyclic group, and R ² represents an aromatic hydrocarbon which may have a substituent.
Examples of the hydrocarbon group for R ¹ include an alkyl group, an alkenyl group, an aryl group, an aralkyl group, and an alkynyl group. Examples of the heterocyclic group include thienyl group, furyl group, pyrrolyl group, imidazolyl group, isothiazolyl group, pyridyl group, indolyl group, quinolyl group, and isoquinolyl group.
Examples of the substituent that they may have include a halogen atom, a short-chain alkyl group, an alkoxy group, a nitro group, and an ester group.

Ｒ^２が芳香族炭化水素の場合には、原料のＮ−アシルヒドラゾンの結晶性が良好で、単離・保存が容易であることが多いため好ましい。このような芳香族炭化水素としては、例えば、フェニル基、トリル基、キシリル基、ビフェニル基、ナフチル基、インデニル基、アントリル基、フェナントリル基等が挙げられ、フェニル基、α−ナフチル基、β−ナフチル基などが好ましく用いられる。これらが有していてもよい置換基としては、ハロゲン、短鎖アルキル基、アルコキシ基等が挙げられる。 When R ² is an aromatic hydrocarbon, it is preferable because the raw material N-acylhydrazone has good crystallinity and is easily isolated and stored. Examples of such aromatic hydrocarbons include phenyl group, tolyl group, xylyl group, biphenyl group, naphthyl group, indenyl group, anthryl group, phenanthryl group and the like. Phenyl group, α-naphthyl group, β- A naphthyl group or the like is preferably used. Examples of the substituent that they may have include a halogen, a short-chain alkyl group, and an alkoxy group.

本発明で用いるプロパギルトリハロシランは下記一般式（化２）で表される。
化２：ＣＨ≡Ｃ−ＣＨ_２−ＳｉＸ_３
Ｘはハロゲン原子、好ましくは塩素原子又は臭素原子を表す。
また、本発明で用いるアレニルトリハロシランは下記一般式（化３）で表される。
化３：ＣＨ_２＝Ｃ＝ＣＨ−ＳｉＸ_３
Ｘは上記と同様に定義される。 The propargyltrihalosilane used in the present invention is represented by the following general formula (Formula 2).
Chemical formula 2: CH≡C—CH ₂ —SiX ₃
X represents a halogen atom, preferably a chlorine atom or a bromine atom.
The allenyltrihalosilane used in the present invention is represented by the following general formula (Formula 3).
Of _{3: CH 2 = C = CH} -SiX 3
X is defined as above.

本発明の反応においては、更に反応系に３級アミンを添加してもよい。３級アミンを添加すると、目的物の収率及び位置選択性を向上させることができる。
３級アミンとしては、トリエチルアミン、Ｎ−メチルモルホリン、Ｎ−メチルピペリジン、Ｎ，Ｎ−ジシクロヘキシルメチルアミン、Ｎ，Ｎ−ジイソプロピルエチルアミンなどが挙げられるが、好ましくはＮ，Ｎ−ジイソプロピルエチルアミンである。 In the reaction of the present invention, a tertiary amine may be further added to the reaction system. When a tertiary amine is added, the yield and regioselectivity of the target product can be improved.
Examples of the tertiary amine include triethylamine, N-methylmorpholine, N-methylpiperidine, N, N-dicyclohexylmethylamine, N, N-diisopropylethylamine, and N, N-diisopropylethylamine is preferable.

本反応系においては溶媒としてジメチルスルホキシド、Ｎ−メチルピロリドン、ヘキサメチルホスホロアミド、ジメチルアセトアミド等を用いることができるが、ジメチルホルムアミド（ＤＭＦ）を用いることが好ましい。ジメチルホルムアミドは安価で安全性も高く、ケイ素原子に配位して求核剤の反応性及び位置選択性を向上させていると考えられる。 In this reaction system, dimethyl sulfoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylacetamide and the like can be used as a solvent, but dimethylformamide (DMF) is preferably used. Dimethylformamide is inexpensive and highly safe, and is thought to coordinate with the silicon atom to improve the reactivity and regioselectivity of the nucleophile.

本発明の方法に於ては、下式に示すようにＮ−アシルヒドラゾンとプロパギルトリハロシランとを反応させることにより、又は

下式に示すようにＮ−アシルヒドラゾンとアレニルトリハロシランとを反応させることにより、

対応するＮ−アシル−Ｎ'−アレニルメチルヒドラジン及びＮ−アシル−Ｎ’−ホモプロパギルヒドラジンが合成される。 In the method of the present invention, by reacting N-acylhydrazone and propargyltrihalosilane as shown in the following formula, or

By reacting N-acylhydrazone with allenyltrihalosilane as shown in the following formula,

The corresponding N-acyl-N′-allenylmethyl hydrazines and N-acyl-N′-homopropargyl hydrazines are synthesized.

この反応は、Ｓ_Ｅ２’タイプの付加反応と考えられる。遷移状態を下式に示す。（１）は反応物にプロパギルトリハロシランを用いた場合、（２）は反応物にアレニルトリハロシランを用いた場合を示す。

This reaction is considered an addition reaction of the S _E 2 ′ type. The transition state is shown in the following equation. (1) shows the case where propargyltrihalosilane is used as the reactant, and (2) shows the case where allenyltrihalosilane is used as the reactant.

これらの反応における位置選択性はほぼ完璧であり、反応物がプロパギルトリハロシランの場合には、下記一般式（化４）
化４：ＣＨ_２＝Ｃ＝ＣＨ−ＣＨＲ^１−ＮＨ−ＮＨＣＯＲ^２
で表されるＮ−アシル−Ｎ'−アレニルメチルヒドラジンが、反応物がアレニルトリハロシランの場合には、下記一般式（化５）
化５：ＣＨ≡Ｃ−ＣＨ_２−ＣＨＲ^１−ＮＨ−ＮＨＣＯＲ^２
（式中、Ｒ^１びＲ^２は上記と同様に定義される。）で表されるＮ−アシル−Ｎ’−ホモプロパギルヒドラジンが唯一の反応物として得られる。 The regioselectivity in these reactions is almost perfect. When the reactant is propargyltrihalosilane, the following general formula (Formula 4)
Embedded image CH ₂ ═C═CH—CHR ¹ —NH—NHCOR ²
N-acyl-N′-allenylmethylhydrazine represented by the following general formula (Chemical Formula 5)
Chemical formula 5: CH≡C—CH ₂ —CHR ¹ —NH—NHCOR ²
(Wherein R ^{1 and} R ² are defined in the same manner as above), and N-acyl-N′-homopropargyl hydrazine is obtained as the only reactant.

原料となるアシルヒドラゾンの濃度は０．０５〜１．０Ｍ程度であり、好ましくは０．１０〜０．５０Ｍである。
プロパギルトリクロロシラン又はアレニルトリクロロシランの量は、アシルヒドラゾンに対するモル比で０．８〜２．０、好ましくは１．０〜１．５である。
プロパギル化反応において添加する３級アミンの量は、アシルヒドラゾンに対するモル比で０〜１０、好ましくは１〜３である。
反応温度は、マイナス１０℃〜室温程度、好ましくは０℃から１０℃であり、反応時間は１時間〜７２時間、好ましくは１０時間〜４８時間程度である。 The concentration of the acyl hydrazone used as a raw material is about 0.05 to 1.0M, preferably 0.10 to 0.50M.
The amount of propargyltrichlorosilane or allenyltrichlorosilane is 0.8 to 2.0, preferably 1.0 to 1.5, as a molar ratio to acylhydrazone.
The amount of the tertiary amine added in the propargylation reaction is 0 to 10, preferably 1 to 3 in terms of a molar ratio with respect to the acyl hydrazone.
The reaction temperature is about minus 10 ° C. to room temperature, preferably 0 ° C. to 10 ° C., and the reaction time is 1 hour to 72 hours, preferably about 10 hours to 48 hours.

このようにして得られたＮ−アシル−Ｎ'−アレニルメチルヒドラジン及びＮ−アシル−Ｎ’−ホモプロパギルヒドラジンは、公知の手法により還元的に窒素−窒素結合を切断することで、それぞれアレニルメチルアミン及びホモプロパギルアミンに容易に変換することができる。この反応は例えば以下のようにして行うことができる（heterocycles 2000, 52, 1143-1162）。即ち、ヒドラジン化合物の溶液に攪拌しながらヨウ化サマリウムのテトラヒドロフラン溶液を滴下する。溶媒はメタノールやエタノールなどのプロトン性溶媒が好ましく、ヒドラジン化合物の濃度は０．０１〜０．５Ｍ程度、反応温度は−２０℃〜１０℃程度、反応時間は５分間〜１時間程度である。ヨウ化サマリウムはヒドラジンに対してモル比で２〜５倍使用する。 The N-acyl-N′-allenylmethyl hydrazine and N-acyl-N′-homopropargyl hydrazine thus obtained can be obtained by reductively cleaving the nitrogen-nitrogen bond by a known method. It can be easily converted to allenylmethylamine and homopropargylamine. This reaction can be performed, for example, as follows (heterocycles 2000, 52, 1143-1162). That is, a tetrahydrofuran solution of samarium iodide is added dropwise to the hydrazine compound solution while stirring. The solvent is preferably a protic solvent such as methanol or ethanol, the concentration of the hydrazine compound is about 0.01 to 0.5 M, the reaction temperature is about −20 ° C. to 10 ° C., and the reaction time is about 5 minutes to 1 hour. Samarium iodide is used in a molar ratio of 2 to 5 times that of hydrazine.

以下、実施例にて本発明を例証するが本発明を限定することを意図するものではない。
合成例１
本合成例では３−フェニルプロパナール−ベンゾイルヒドラゾン（化合物４ａ）を合成した。
Ｎ−ベンゾイルヒドラジン（50 mmol）をＴＨＦ(100 ml)に溶解し、３−フェニルプロパナール（55 mmol）と濃塩酸（１滴）を加えた後１時間還流した。室温に戻した後、氷冷し、析出した沈殿を濾取した。酢酸エチル−ヘキサンから再結晶して３−フェニルプロパナール−ベンゾイルヒドラゾンを白色結晶として収率７５％で得た。生成物の物性を以下に示す。
3-Phenylpropanal benzoylhydrazone(化合物4a): mp 130℃; ¹H NMR (CDCl₃, 400 MHz): δ 2.67 (t, J = 7.3 Hz, 2H), 2.84 (t, J = 7.32 Hz, 2H), 7.16-7.29 (m, 5H), 7.38 (dd, J = 7.8, 7.4 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.64 (br s, 1H), 7.80 (d, J = 7.8 Hz, 2H), 9.61 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ32.8, 33.9, 126.2, 127.4, 128.4, 128.6, 131.9, 133.1, 140.5, 151.6, 164.2; IR (KBr): 3238, 3059, 1653, 1284, 1045, 874, 789, 696 cm^-1; Anal. Calcd for C₁₆H₁₆N₂O: C 76.16; H 6.39; N 11.10. Found: C 76.29; H 6.58; N 11.14 The following examples illustrate the invention but are not intended to limit the invention.
Synthesis example 1
In this synthesis example, 3-phenylpropanal-benzoylhydrazone (compound 4a) was synthesized.
N-benzoylhydrazine (50 mmol) was dissolved in THF (100 ml), 3-phenylpropanal (55 mmol) and concentrated hydrochloric acid (1 drop) were added, and the mixture was refluxed for 1 hour. After returning to room temperature, the mixture was ice-cooled, and the deposited precipitate was collected by filtration. Recrystallization from ethyl acetate-hexane gave 3-phenylpropanal-benzoylhydrazone as white crystals in a yield of 75%. The physical properties of the product are shown below.
3-Phenylpropanal benzoylhydrazone (compound 4a): mp 130 ° C; ¹ H NMR (CDCl ₃ , 400 MHz): δ 2.67 (t, J = 7.3 Hz, 2H), 2.84 (t, J = 7.32 Hz, 2H), 7.16 -7.29 (m, 5H), 7.38 (dd, J = 7.8, 7.4 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.64 (br s, 1H), 7.80 (d, J = 7.8 Hz , 2H), 9.61 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ32.8, 33.9, 126.2, 127.4, 128.4, 128.6, 131.9, 133.1, 140.5, 151.6, 164.2; IR (KBr ): 3238, 3059, 1653, 1284, 1045, 874, 789, 696 cm ^-1 ; Anal.Calcd for C ₁₆ H ₁₆ N ₂ O: C 76.16; H 6.39; N 11.10. Found: C 76.29; H 6.58; N 11.14

化合物４ｂ〜４ｊも同様の方法により合成した。以下、これらの分析データを記す。
化合物4b:
Benzaldehyde p-methoxybenzoylhydrarone : Mp 201-202℃; ¹H NMR (300 MHz, CDCl₃) δ 3.84 (s, 3H), 6.93 (br d, J = 8.7 Hz, 2H), 7.30-7.37 (m, 3H), 7.70 (m, 2H), 7.86 (m, 1H), 8.30 (br s, 1H); IR (KBr) 3201, 1633, 1257, 1174, 845, 766, 696 cm^-1; Anal. Calcd for C_l5H₁₄N₂O₂: C, 70.85; H, 5,55; N, 11.02. Found: C, 70.66; H, 5.69; N, l0.90.
化合物4c:
p-Chlorobenzaldehyde benzoylhydrazone : Mp 174.7- 174.8℃; ¹H NMR (600 MHz, DMSO-d₆) δ 7,51-7.54 (m, 4H), 7.59 (t, J = 7.6 Hz, 1H), 7.75 (d, J = 8.9 Hz, 2H), 7.90 (d, J = 7.6 Hz, 2H), 8.43 (s, 1H), 11.95 (br s, 1H); ¹³C NMR (150 MHz, DMSO-d₆) δ 127.7, 128.6, 128.8, 129.1, 132.0, 133.3, 134.6, 146.5, 163.3; IR (KBr) 3292, 3062, 1667, 1605, 1542, 1485, 1282, 1146, 1088, 826, 679 cm^-1; HR-ESIMS calcd for C_l4H_l2ClN₂0 (M+H⁺) 259.0593, found 259.0605.
化合物4d:
p-Anisaldehyde benzoylhydrazone : Mp 155.5-155.6℃; ¹H NMR (600 MHz, CDCl₃) δ 3.78 (s, 3H), 6.81 (s, 1H), 7.38-7.52 (m, 3H), 7.62 (d. J = 5.5 Hz, 2H), 7.89 (d, J = 7.6 Hz, 2H), 8.35 (d, J = 6.2 Hz, 1H), 10.18 (br s, 1H) ¹³C NMR (150 MHz CDCl₃) δ 55.3, 114.0, 136.3, 127.4, 128.6, 129.4, 131.9, 133.3, 148.8, 161.4, 164.4; IR (KBr) 3203, 1641, 1605, 1546, 1256, 1168, 1026, 833, 696 cm^-1; Anal. Calcd for C_l5H₁₄N₂O₂: C, 70.85; H, 5.55; N, 11.02. Found: C, 70.99; H, 5.71; N, 11.13.
化合物4e:
Cinnamaldehyde benzoylhydrazone : Mp 145-146℃; ¹H NMR (600 MHz, DMSO-d₆)δ 7.06 (d, J = 7.6 Hz, 2H), 7.31-7.40 (m, 3H), 7.50-7.63 (m, 5H), 7.89 (d, J = 7.6 Hz, 2H), 8.23 (d, J = 7. 6 Hz, 1H), 11.8 (s, 1H); ¹³C NMR (150 MHz, DMSO-d₆) δ 125.7, 127.2, 127. 7, 128.6, 128.9, 131.8, 133.4, 136.0, 139.2, 149.8, 163.1; IR (KBr) 3199, 3033, 1672, 1547, 1371, 1252, 1146, 1041, 800, 710 cm^-1; Anal. Calcd for C_l1H₁₂N₂O₃: C, 59.99; H, 5.49; N, 12.76. Found: C, 60.06; H, 5.61; N, 12.56.
化合物4g:
2-Methylpropanal benzoylhydrazone : Mp 129.6-129.9℃; ¹H NMR (600 MHz, CDCl₃) δ 1.09 (d, J = 6.9 Hz, 6H), 2.61-2.66 (m, 1H), 7.37-7.53 (m, 4H), 7.81 (d, J = 7.6 Hz, 2H), 9.79 (s, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 19.9, 31.6, 127,4, 128.5, 131.8, 133.3, 167,6, 164.4; IR (KBr) 3234, 3071, 2965, 1650, 1549, 1354, 1282, 1145, 1031, 887, 694 cm^-1; Anal. Calcd for C_l1H₁₄N₂O: C, 69.45; H, 7.46; N, 14.73. Found: C, 69.63; H, 7.53; N, 14.65.
化合物4h:
Cyclohexanecarboxaldehyde benzoylhydrazone : Mp 170℃; ¹H NMR (600 MHz. CDCl₃) δ 1.13-1.32 (m, 6H), 1.65-1.81 (m, 4H), 2.34-2.39 (m, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.46-7.53 (m, 2H), 7.80 (d, J = 7.6 Hz, 2H), 9.80 (br s, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 25.3, 25.8, 30.1, 4O.9, 127.4, 128.5, 131.8, 133.3, 156.7, 164.3; IR (KBr) 3201, 2925, 1645, 1556, 1448, 1147, 1043, 694 cm^-1; Anal. Calcd for C_l4H₁₈N₂O: C, 73.01; H, 7.88; N, 12.16. Found C, 73.25; H, 8.03; N, 12.12.
化合物4j:
Ethyl benzoylhydrazonoacetate : Mp 194℃; ¹H NMR (600 MHz, CDCl₃) δ l.39 (t, J = 7.6 Hz, 3H), 4.34 (q, J = 7.6, 2H), 7.12 (br s, 1H), 7.52 (t, J = 7.6 Hz, 2H), 7.61 (t. J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ 14.0, 61.9, 127.7, 128.8, 129.9, 131.8, 132.9, 162.5; IR (KBr) 3267, 3060, 1647, 1539, 1367, 1281, 1132, 1047, 985, 900, 748, 690 cm^-1; Anal. Calcd for C_l6H₁₄ClN₂O: C, 76.78; H, 5.64; N, 11.19. Found: C, 76.83; H, 5.83; N, 11.17. Compounds 4b to 4j were synthesized by the same method. These analysis data are described below.
Compound 4b:
Benzaldehyde p-methoxybenzoylhydrarone: Mp 201-202 ℃; ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.84 (s, 3H), 6.93 (br d, J = 8.7 Hz, 2H), 7.30-7.37 (m, 3H) , 7.70 (m, 2H), 7.86 (m, 1H), 8.30 (br s, 1H); IR (KBr) 3201, 1633, 1257, 1174, 845, 766, 696 cm ^-1 ; Anal. Calcd for C _l5 H ₁₄ N ₂ O ₂ : C, 70.85; H, 5,55; N, 11.02.Found: C, 70.66; H, 5.69; N, l0.90.
Compound 4c:
p-Chlorobenzaldehyde benzoylhydrazone: Mp 174.7- 174.8 ℃; ¹ H NMR (600 MHz, DMSO-d ₆ ) δ 7,51-7.54 (m, 4H), 7.59 (t, J = 7.6 Hz, 1H), 7.75 (d , J = 8.9 Hz, 2H), 7.90 (d, J = 7.6 Hz, 2H), 8.43 (s, 1H), 11.95 (br s, 1H); ¹³ C NMR (150 MHz, DMSO-d ₆ ) δ 127.7 , 128.6, 128.8, 129.1, 132.0, 133.3, 134.6, 146.5, 163.3; IR (KBr) 3292, 3062, 1667, 1605, 1542, 1485, 1282, 1146, 1088, 826, 679 cm ^-1 ; HR-ESIMS calcd _{_{_{for C l4 H l2 ClN 2 0}}} (M + H +) 259.0593, found 259.0605.
Compound 4d:
p-Anisaldehyde benzoylhydrazone: Mp 155.5-155.6 ℃; ¹ H NMR (600 MHz, CDCl ₃ ) δ 3.78 (s, 3H), 6.81 (s, 1H), 7.38-7.52 (m, 3H), 7.62 (d. J = 5.5 Hz, 2H), 7.89 (d, J = 7.6 Hz, 2H), 8.35 (d, J = 6.2 Hz, 1H), 10.18 (br s, 1H) ¹³ C NMR (150 MHz CDCl ₃ ) δ 55.3, 114.0, 136.3, 127.4, 128.6, 129.4, 131.9, 133.3, 148.8, 161.4, 164.4; IR (KBr) 3203, 1641, 1605, 1546, 1256, 1168, 1026, 833, 696 cm ^-1 ; Anal. Calcd for C _l5 H ₁₄ N ₂ O ₂ : C, 70.85; H, 5.55; N, 11.02.Found: C, 70.99; H, 5.71; N, 11.13.
Compound 4e:
Cinnamaldehyde benzoylhydrazone: Mp 145-146 ° C; ¹ H NMR (600 MHz, DMSO-d ₆ ) δ 7.06 (d, J = 7.6 Hz, 2H), 7.31-7.40 (m, 3H), 7.50-7.63 (m, 5H ), 7.89 (d, J = 7.6 Hz, 2H), 8.23 (d, J = 7.6 Hz, 1H), 11.8 (s, 1H); ¹³ C NMR (150 MHz, DMSO-d ₆ ) δ 125.7, 127.2, 127. 7, 128.6, 128.9, 131.8, 133.4, 136.0, 139.2, 149.8, 163.1; IR (KBr) 3199, 3033, 1672, 1547, 1371, 1252, 1146, 1041, 800, 710 cm ^-1 ; Anal Calcd for C _l1 H ₁₂ N ₂ O ₃ : C, 59.99; H, 5.49; N, 12.76. Found: C, 60.06; H, 5.61; N, 12.56.
Compound 4g:
2-Methylpropanal benzoylhydrazone: Mp 129.6-129.9 ℃; ¹ H NMR (600 MHz, CDCl ₃ ) δ 1.09 (d, J = 6.9 Hz, 6H), 2.61-2.66 (m, 1H), 7.37-7.53 (m, 4H ), 7.81 (d, J = 7.6 Hz, 2H), 9.79 (s, 1H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 19.9, 31.6, 127,4, 128.5, 131.8, 133.3, 167,6, 164.4; IR (KBr) 3234, 3071, 2965, 1650, 1549, 1354, 1282, 1145, 1031, 887, 694 cm ^-1 ; Anal.Calcd for C _l1 H ₁₄ N ₂ O: C, 69.45; H, 7.46 ; N, 14.73. Found: C, 69.63; H, 7.53; N, 14.65.
Compound 4h:
Cyclohexanecarboxaldehyde benzoylhydrazone: Mp 170 ° C; ¹ H NMR (600 MHz. CDCl ₃ ) δ 1.13-1.32 (m, 6H), 1.65-1.81 (m, 4H), 2.34-2.39 (m, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.46-7.53 (m, 2H), 7.80 (d, J = 7.6 Hz, 2H), 9.80 (br s, 1H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 25.3, 25.8 , 30.1, 4O.9, 127.4, 128.5 , 131.8, 133.3, 156.7, 164.3; IR (KBr) 3201, 2925, 1645, 1556, 1448, 1147, 1043, 694 cm -1;. Anal Calcd for C l4 H 18 N ₂ O: C, 73.01; H, 7.88; N, 12.16. Found C, 73.25; H, 8.03; N, 12.12.
Compound 4j:
Ethyl benzoylhydrazonoacetate: Mp 194 ℃; ¹ H NMR (600 MHz, CDCl ₃ ) δ l.39 (t, J = 7.6 Hz, 3H), 4.34 (q, J = 7.6, 2H), 7.12 (br s, 1H) , 7.52 (t, J = 7.6 Hz, 2H), 7.61 (t.J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 2H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 14.0, 61.9, 127.7, 128.8, 129.9, 131.8, 132.9, 162.5; IR (KBr) 3267, 3060, 1647, 1539, 1367, 1281, 1132, 1047, 985, 900, 748, 690 cm ^-1 ; Anal.Calcd for C _l6 H ₁₄ ClN ₂ O: C, 76.78; H, 5.64; N, 11.19.Found: C, 76.83; H, 5.83; N, 11.17.

合成例２
本合成例では以下の手順でプロパギルトリクロロシラン（化合物２）を調製した。
フッ化銅（II）(0.50 mmol、和光純薬工業）を含む乾燥エーテル(20 ml)中に、攪拌しながら２０℃でＮ，Ｎ−ジイソプロピルエチルアミン(40 mmol、東京化成工業)、塩化プロパギル(20 mmol、東京化成工業)又は臭化プロパギル(20 mmol、東京化成工業)、トリクロロシラン(44 mmol、東京化成工業)を順次滴下した。混合物を２０℃で３〜１２時間攪拌し、反応液の一部を採取し重クロロホルムで希釈し、^１Ｈ−ＮＭＲを測定し収率及び生成した化合物２とアレニルトリクロロシラン（化合物３）の比率を決定した。収率７５％、化合物２：化合物３＝>９９：１。 Synthesis example 2
In this synthesis example, propargyltrichlorosilane (compound 2) was prepared by the following procedure.
In dry ether (20 ml) containing copper (II) fluoride (0.50 mmol, Wako Pure Chemical Industries, Ltd.) at 20 ° C. with stirring, N, N-diisopropylethylamine (40 mmol, Tokyo Chemical Industry), propargyl chloride ( 20 mmol, Tokyo Chemical Industry) or propargyl bromide (20 mmol, Tokyo Chemical Industry) and trichlorosilane (44 mmol, Tokyo Chemical Industry) were successively added dropwise. The mixture was stirred at 20 ° C. for 3 to 12 hours, a part of the reaction solution was collected and diluted with deuterated chloroform, and ¹ H-NMR was measured to determine the yield and yield of compound 2 and allenyltrichlorosilane (compound 3). The ratio was determined. Yield 75%, Compound 2: Compound 3 => 99: 1.

合成例３
本合成例では以下の手順でアレニルトリクロロシラン（化合物３）を調整した。
ビス（２，４−ペンタジオネート）ニッケル（II）(0.50 mmol、和光純薬工業）を含む乾燥エーテル(20 ml)中に、攪拌しながら２０℃でＮ，Ｎ−ジイソプロピルエチルアミン(40 mmol)、塩化プロパギル(20 mmol)又は臭化プロパギル(20 mmol)、トリクロロシラン(44 mmol)を順次滴下した。混合物を２０℃で３〜１２時間攪拌し、反応液の一部を採取し重クロロホルムで希釈し、^１Ｈ−ＮＭＲを測定し収率及び生成した化合物２と化合物３の比率を決定した。収率７５％、化合物２：化合物３＝１：>９９。 Synthesis example 3
In this synthesis example, allenyltrichlorosilane (compound 3) was prepared by the following procedure.
N, N-Diisopropylethylamine (40 mmol) at 20 ° C. with stirring in dry ether (20 ml) containing bis (2,4-pentadionate) nickel (II) (0.50 mmol, Wako Pure Chemical Industries) , Propargyl chloride (20 mmol) or propargyl bromide (20 mmol), and trichlorosilane (44 mmol) were successively added dropwise. The mixture was stirred at 20 ° C. for 3 to 12 hours, a part of the reaction solution was collected and diluted with deuterated chloroform, and ¹ H-NMR was measured to determine the yield and the ratio of compound 2 and compound 3 produced. Yield 75%, Compound 2: Compound 3 = 1:> 99.

本実施例では、Ｎ'−（１−フェニルヘキサ−４，５−ジエン−３−イル）ベンゾヒドラジド（化合物５ａ）を合成した。
合成例１で得た３−フェニルプロパナール−ベンゾイルヒドラゾン（化合物４a、1.0 mmol）のＤＭＦ(10 ml、和光純薬工業)溶液を０℃に冷却し、合成例２で調整したプロパギルトリクロロシラン（化合物２）のエーテル溶液（1.5 mmol、濃度はＮＭＲで決定）を滴下した。２４時間攪拌後トリエチルアミン(7.5 mmol) のメタノール溶液を滴下して反応を停止した。さらに３０分間攪拌し、室温まで昇温、水を加えた後、塩化メチレンで３回抽出した。有機相を併せて飽和食塩水で洗浄し、無水硫酸ナトリウム上で乾燥した。乾燥剤を濾別後、減圧濃縮し、得られた残渣を調製用薄層クロマトグラフィー（展開液：ヘキサン／酢酸エチル）で精製して化合物５ａを収率９３％で得た。生成物の物性データを以下に示す。
N'-(1-phenylhexa-4,5-dien-3-yl)benzohydrazide (化合物5a) (表１, entry 1): ¹H NMR (CDCl₃, 400 MHz): δ1.89 (dt, J = 7.2 Hz, J = 8.1 Hz, 2H), 2.25 (br s, 1H), 2.70 (dt, J = 4.5 Hz, J = 8.1 Hz, 2H), 3.56 (m, 1H), 4.81 (dd, J = 2.4 Hz, J = 7.2 Hz, 2H), 5.18 (dt, J = 6.0 Hz, J = 7.2 Hz, 1H), 7.10-7.28 (m, 5H), 7.38-7.59 (m, 3H), 7.70-7.91 (m, 3H); ¹³C NMR (CDCl₃, 100 MHz): ( 31.4, 34.3, 58.0, 77.3, 94.4, 125.9, 127.5, 128.3, 128.5, 128.6, 132.6, 134.7, 141.9, 167.0, 207.5; IR (neat): 3286, 2932, 1954, 1711, 1638, 1450, 895, 700 cm^-1; HRMS (ESI) calcd. for C₁₉H₂₀N_2O [M+H]⁺: m/z 292.1576, found: m/z 292.1578. In this example, N ′-(1-phenylhexa-4,5-dien-3-yl) benzohydrazide (Compound 5a) was synthesized.
The DMF (10 ml, Wako Pure Chemical Industries) solution of 3-phenylpropanal-benzoylhydrazone (Compound 4a, 1.0 mmol) obtained in Synthesis Example 1 was cooled to 0 ° C., and propargyltrichlorosilane prepared in Synthesis Example 2 was used. An ether solution (1.5 mmol, concentration determined by NMR) of (Compound 2) was added dropwise. After stirring for 24 hours, a methanol solution of triethylamine (7.5 mmol) was added dropwise to stop the reaction. The mixture was further stirred for 30 minutes, warmed to room temperature, added with water, and extracted three times with methylene chloride. The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The desiccant was filtered off and concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer chromatography (developing solution: hexane / ethyl acetate) to obtain Compound 5a in 93% yield. The physical property data of the product is shown below.
N '-(1-phenylhexa-4,5-dien-3-yl) benzohydrazide (Compound 5a) (Table 1, entry 1): ¹ H NMR (CDCl ₃ , 400 MHz): δ1.89 (dt, J = 7.2 Hz, J = 8.1 Hz, 2H), 2.25 (br s, 1H), 2.70 (dt, J = 4.5 Hz, J = 8.1 Hz, 2H), 3.56 (m, 1H), 4.81 (dd, J = 2.4 Hz, J = 7.2 Hz, 2H), 5.18 (dt, J = 6.0 Hz, J = 7.2 Hz, 1H), 7.10-7.28 (m, 5H), 7.38-7.59 (m, 3H), 7.70-7.91 (m , 3H); ¹³ C NMR (CDCl ₃ , 100 MHz): (31.4, 34.3, 58.0, 77.3, 94.4, 125.9, 127.5, 128.3, 128.5, 128.6, 132.6, 134.7, 141.9, 167.0, 207.5; IR (neat) : 3286, 2932, 1954, 1711, 1638, 1450, 895, 700 cm ^-1 ; HRMS (ESI) calcd.for C ₁₉ H ₂₀ N _2O [M + H] ⁺ : m / z 292.1576, found: m / z 292.1578.

次に、この反応の基質に対する依存性を調べた。その結果を表１に示す。

Next, the dependence of this reaction on the substrate was examined. The results are shown in Table 1.

芳香族ヒドラゾン（化合物４ｂ、４ｃ）及びα−ヒドラゾノエステル（化合物４ｊ）からは高い選択性と高収率（３％〜８７％）で目的物が得られた。脂肪族化合物（化合物４ｆ〜ｈ）及びα、β−不飽和化合物もスムースに反応が進行し、完全な位置選択性で対応するＮ−アシル−Ｎ'−アレニルメチルヒドラジンが得られた（収率７０％〜８０％、entries 5-8)。
一方、芳香族基質（化合物４ｄ）と立体障害のある基質(化合物４ｉ)の場合は若干収率が低下した(entry 4, 9)。ほとんど全ての場合において位置選択性は完璧であったが、芳香族ヒドラゾンを用いた場合（化合物４ｂ−ｄ）のみ、僅かに選択性が低下し、ホモプロパギル体の生成が検出された(entry 2-4)。
その結果、本発明の方法が特に基質の構造や性質に依存しないことが判った。 From the aromatic hydrazone (compounds 4b and 4c) and the α-hydrazono ester (compound 4j), the desired product was obtained with high selectivity and high yield (3% to 87%). The reaction of the aliphatic compound (compounds 4f to h) and the α, β-unsaturated compound also proceeded smoothly, and the corresponding N-acyl-N′-allenylmethylhydrazine was obtained with complete regioselectivity (concentration). Rate 70% -80%, entries 5-8).
On the other hand, in the case of the aromatic substrate (compound 4d) and the sterically hindered substrate (compound 4i), the yield decreased slightly (entry 4, 9). In almost all cases, the regioselectivity was perfect, but only when aromatic hydrazone was used (compounds 4b-d), the selectivity slightly decreased and the formation of homopropargyl was detected (entry 2- Four).
As a result, it has been found that the method of the present invention is not particularly dependent on the structure and properties of the substrate.

以下、得られた化合物５ｂ〜５ｊの物性データを示す。
N'(1-Phenylbuta-2,3-dienyl)benzohydrazide (5b):
(表１, entry 2; R = Ph)
¹H NMR (CDCl₃, 400 MHz): δ 2.92 (br s, 1H), 4.40-4.50 (m, 1H), 4.75 (dd, J = 2.5 Hz, J = 7.0 Hz, 2H), 5.43 (dt, J = 6.3 Hz, J = 7.0 Hz, 1H), 7.02-7.21 (m, 5H), 7.39-7.62 (m, 3H), 7.76-7.91 (m, 2H); 8.23 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ59.7, 77.8, 92.7, 126.9, 127.2, 127.7, 128.9, 129.2, 132.0, 134.5, 142.8, 166.0, 207.9.
N'-(1-(4-Chlorophenyl)buta-2,3-dienyl)benzohydrazide (5c):
(表１, entry 3; R = 4-ClC₆H₄)
¹H NMR (CDCl₃, 400 MHz): δ3.36 (br s, 1H), 4.47-4.59 (m, 1H), 4.73 (dd, J = 2.4 Hz, J = 7.1 Hz, 2H), 5.48 (dt, J = 6.0 Hz, J = 7.1 Hz, 1H), 6.95 (d, J = 9.6 Hz, 2H), 7.19 (dd, J = 9.6 Hz, 2H), 7.35-7.59 (m, 3H), 7.79-7.95 (m, 2H); 8.46 (br s, 1H), ¹³C NMR (CDCl₃, 100 MHz): δ60.2, 77.6, 92.0, 127.4, 128.6, 128.8, 132.5, 132.8, 134.1, 141.7, 165.9, 208.0.
N'-(1-(4-Methoxyphenyl)buta-2,3-dienyl)benzohydrazide (5d):
(表１, entry 4; R = 4-MeOC₆H₄)
¹H NMR (CDCl₃, 400 MHz): δ 3.27 (br s, 1H), 3.76 (s, 3H), 4.42-4.47 (m, 1H), 4.70 (dd, J = 2.3 Hz, J = 7.0 Hz, 2H), 5.33 (dt, J = 6.3 Hz, J = 7.0 Hz, 1H), 6.67 (dt, J = 9.3 Hz, 2H), 6.90 (dt, J = 9.3 Hz, 2H), 7.38-7.57 (m, 3H), 7.77-7.89 (m, 2H); 8.18 (br s, 1H), ¹³C NMR (CDCl₃, 100 MHz): δ 55.9, 59.5, 76.8, 92.0, 114.0, 127.9, 128.2, 128.8, 132.6, 134.0, 135.5, 158.9, 166.3, 208.0.
N'-((E)-1-Phenylhexa-1,4,5-trien-3-yl)benzohydrazide (5e):
(表１, entry 5; R = (E)-PhCH=CH)
¹H NMR (CDCl₃, 400 MHz): δ2.87 (br s, 1H), 3.90-4.04 (m, 1H), 4.78 (dd, J = 2.6 Hz, J = 7.3 Hz, 2H), 5.48 (dt, J = 6.2 Hz, J = 7.3 Hz, 1H), 6.16-6.21 (m, 1H), 6.50-6.56 (m, 1H), 7.07-7.35 (m, 5H), 7.38-7.60 (m, 3H), 7.79-7.97 (m, 2H), 8.26 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ58.9, 76.8, 92.5, 123.7, 126.0, 127.5, 128.1, 128.8, 129.0, 129.2, 132.2, 134.5, 135.0, 165.7, 208.1.
N'-(Hepta-1,2-dien-4-yl)benzohydrazide (5f):
(表１, entry 6; R = ⁿPr)
¹H NMR (CDCl₃, 400 MHz): δ0.91-0.98 (m, 3H), 1.35-1.59 (m, 4H), 3.20-3.39 (m, 2H), 4.68 (dd, J = 2.1 Hz, J = 7.4 Hz, 2H), 5.31 (dt, J = 6.0 Hz, J = 7.4 Hz, 1H), 7.40-7.59 (m, 3H), 7.72-7.86 (m, 2H), 8.27 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ14.5, 17.9, 32.4, 55.8, 75.8, 93.0, 127.5, 128.6, 131.9, 134.1, 165.8, 207.4.
N'-(2-Methylhexa-4,5-dien-3-yl)benzohydrazide (5g):
(表１, entry 7; R = ⁱPr)
¹H NMR (CDCl₃, 400 MHz): δ1.05 (d, J = 7.5 Hz, 6H), 2.17 (m, 1H), 3.20-3.38 (m, 2H), 4.75 (dd, J = 2.5 Hz, J = 7.2 Hz, 2H), 5.44 (dt, J = 6.4 Hz, J = 7.2 Hz, 1H), 7.37-7.55 (m, 3H), 7.75-7.94 (m, 2H), 8.15 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ17.8, 29.6, 63.3, 75.7, 93.6, 127.4, 128.7, 132.2, 134.6, 165.6, 207.7.
N'-(1-Cyclohexylbuta-2,3-dienyl)benzohydrazide (5h):
(表１, entry 8; R = Cy)
¹H NMR (CDCl₃, 400 MHz): δ1.32-1.56 (m, 10H), 1.68-1.75 (m, 1H), 3.17 (br s, 1H), 3.27-3.36 (m, 1H), 4.66 (dd, J = 2.3 Hz, J = 6.9 Hz, 2H), 5.31 (dt, J = 6.1 Hz, J = 6.9 Hz, 1H), 7.32-7.51 (m, 3H), 7.79-8.15 (m, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ26.7, 27.8, 28.2, 29.9, 56.7, 76.2, 92.8, 127.5, 128.5, 132.0, 134.3, 165.9, 207.9.
N'-(2,2-Dimethylhexa-4,5-dien-3-yl)benzohydrazide (5i):
(表１, entry 9; R = ^tBu)
¹H NMR (CDCl₃, 400 MHz): δ1.02 (s, 9H), 3.16-3.28 (m, 2H), 4.75 (dd, J = 2.3 Hz, J = 7.0 Hz, 2H), 5.40 (dt, J = 6.0 Hz, J = 7.0 Hz, 1H), 7.42-7.64 (m, 3H), 7.73-7.96 (m, 2H), 8.30 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 24.2, 34.8, 72.3, 75.5, 93.6, 127.5, 128.4, 131.9, 134.4, 165.8, 207.8.
Ethyl 2-(Benzamido)penta-3,4-dienoate (5j):
(表１, entry 10; R = CO₂Et)
¹H NMR (CDCl₃, 400 MHz): δ1.28 (t, J = 7.1 Hz, 3H), 3.37 (br s, 1H), 4.10-4.21 (m, 3H), 4.74 (dd, J = 2.5 Hz, J = 7.2 Hz, 2H), 5.39 (dt, J = 6.2 Hz, J = 7.2 Hz, 1H), 7.40-7.55 (m, 3H), 7.74-7.90 (m, 2H), 8.45 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ14.1, 61.0, 63.9, 76.9, 92.7, 127.5, 128.8, 132.5, 134.3, 165.9, 171.5, 208.0. Hereinafter, physical property data of the obtained compounds 5b to 5j are shown.
N '(1-Phenylbuta-2,3-dienyl) benzohydrazide (5b):
(Table 1, entry 2; R = Ph)
¹ H NMR (CDCl ₃ , 400 MHz): δ 2.92 (br s, 1H), 4.40-4.50 (m, 1H), 4.75 (dd, J = 2.5 Hz, J = 7.0 Hz, 2H), 5.43 (dt, J = 6.3 Hz, J = 7.0 Hz, 1H), 7.02-7.21 (m, 5H), 7.39-7.62 (m, 3H), 7.76-7.91 (m, 2H); 8.23 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 59.7, 77.8, 92.7, 126.9, 127.2, 127.7, 128.9, 129.2, 132.0, 134.5, 142.8, 166.0, 207.9.
N '-(1- (4-Chlorophenyl) buta-2,3-dienyl) benzohydrazide (5c):
(Table 1, entry 3; R = 4-ClC ₆ H ₄ )
¹ H NMR (CDCl ₃ , 400 MHz): δ3.36 (br s, 1H), 4.47-4.59 (m, 1H), 4.73 (dd, J = 2.4 Hz, J = 7.1 Hz, 2H), 5.48 (dt , J = 6.0 Hz, J = 7.1 Hz, 1H), 6.95 (d, J = 9.6 Hz, 2H), 7.19 (dd, J = 9.6 Hz, 2H), 7.35-7.59 (m, 3H), 7.79-7.95 (m, 2H); 8.46 (br s, 1H), ¹³ C NMR (CDCl ₃ , 100 MHz): δ60.2, 77.6, 92.0, 127.4, 128.6, 128.8, 132.5, 132.8, 134.1, 141.7, 165.9, 208.0 .
N '-(1- (4-Methoxyphenyl) buta-2,3-dienyl) benzohydrazide (5d):
(Table 1, entry 4; R = 4-MeOC ₆ H ₄ )
¹ H NMR (CDCl ₃ , 400 MHz): δ 3.27 (br s, 1H), 3.76 (s, 3H), 4.42-4.47 (m, 1H), 4.70 (dd, J = 2.3 Hz, J = 7.0 Hz, 2H), 5.33 (dt, J = 6.3 Hz, J = 7.0 Hz, 1H), 6.67 (dt, J = 9.3 Hz, 2H), 6.90 (dt, J = 9.3 Hz, 2H), 7.38-7.57 (m, 3H), 7.77-7.89 (m, 2H); 8.18 (br s, 1H), ¹³ C NMR (CDCl ₃ , 100 MHz): δ 55.9, 59.5, 76.8, 92.0, 114.0, 127.9, 128.2, 128.8, 132.6, 134.0, 135.5, 158.9, 166.3, 208.0.
N '-((E) -1-Phenylhexa-1,4,5-trien-3-yl) benzohydrazide (5e):
(Table 1, entry 5; R = (E) -PhCH = CH)
¹ H NMR (CDCl ₃ , 400 MHz): δ2.87 (br s, 1H), 3.90-4.04 (m, 1H), 4.78 (dd, J = 2.6 Hz, J = 7.3 Hz, 2H), 5.48 (dt , J = 6.2 Hz, J = 7.3 Hz, 1H), 6.16-6.21 (m, 1H), 6.50-6.56 (m, 1H), 7.07-7.35 (m, 5H), 7.38-7.60 (m, 3H), 7.79-7.97 (m, 2H), 8.26 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ58.9, 76.8, 92.5, 123.7, 126.0, 127.5, 128.1, 128.8, 129.0, 129.2, 132.2, 134.5, 135.0, 165.7, 208.1.
N '-(Hepta-1,2-dien-4-yl) benzohydrazide (5f):
(Table 1, entry 6; R = ⁿ Pr)
¹ H NMR (CDCl ₃ , 400 MHz): δ0.91-0.98 (m, 3H), 1.35-1.59 (m, 4H), 3.20-3.39 (m, 2H), 4.68 (dd, J = 2.1 Hz, J = 7.4 Hz, 2H), 5.31 (dt, J = 6.0 Hz, J = 7.4 Hz, 1H), 7.40-7.59 (m, 3H), 7.72-7.86 (m, 2H), 8.27 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ14.5, 17.9, 32.4, 55.8, 75.8, 93.0, 127.5, 128.6, 131.9, 134.1, 165.8, 207.4.
N '-(2-Methylhexa-4,5-dien-3-yl) benzohydrazide (5g):
(Table 1, entry 7; R = ⁱ Pr)
¹ H NMR (CDCl ₃ , 400 MHz): δ1.05 (d, J = 7.5 Hz, 6H), 2.17 (m, 1H), 3.20-3.38 (m, 2H), 4.75 (dd, J = 2.5 Hz, J = 7.2 Hz, 2H), 5.44 (dt, J = 6.4 Hz, J = 7.2 Hz, 1H), 7.37-7.55 (m, 3H), 7.75-7.94 (m, 2H), 8.15 (br s, 1H) ; ¹³ C NMR (CDCl ₃ , 100 MHz): δ17.8, 29.6, 63.3, 75.7, 93.6, 127.4, 128.7, 132.2, 134.6, 165.6, 207.7.
N '-(1-Cyclohexylbuta-2,3-dienyl) benzohydrazide (5h):
(Table 1, entry 8; R = Cy)
¹ H NMR (CDCl ₃ , 400 MHz): δ1.32-1.56 (m, 10H), 1.68-1.75 (m, 1H), 3.17 (br s, 1H), 3.27-3.36 (m, 1H), 4.66 ( dd, J = 2.3 Hz, J = 6.9 Hz, 2H), 5.31 (dt, J = 6.1 Hz, J = 6.9 Hz, 1H), 7.32-7.51 (m, 3H), 7.79-8.15 (m, 3H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ26.7, 27.8, 28.2, 29.9, 56.7, 76.2, 92.8, 127.5, 128.5, 132.0, 134.3, 165.9, 207.9.
N '-(2,2-Dimethylhexa-4,5-dien-3-yl) benzohydrazide (5i):
(Table 1, entry 9; R = ^t Bu)
¹ H NMR (CDCl ₃ , 400 MHz): δ1.02 (s, 9H), 3.16-3.28 (m, 2H), 4.75 (dd, J = 2.3 Hz, J = 7.0 Hz, 2H), 5.40 (dt, J = 6.0 Hz, J = 7.0 Hz, 1H), 7.42-7.64 (m, 3H), 7.73-7.96 (m, 2H), 8.30 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 24.2, 34.8, 72.3, 75.5, 93.6, 127.5, 128.4, 131.9, 134.4, 165.8, 207.8.
Ethyl 2- (Benzamido) penta-3,4-dienoate (5j):
(Table 1, entry 10; R = CO ₂ Et)
¹ H NMR (CDCl ₃ , 400 MHz): δ1.28 (t, J = 7.1 Hz, 3H), 3.37 (br s, 1H), 4.10-4.21 (m, 3H), 4.74 (dd, J = 2.5 Hz , J = 7.2 Hz, 2H), 5.39 (dt, J = 6.2 Hz, J = 7.2 Hz, 1H), 7.40-7.55 (m, 3H), 7.74-7.90 (m, 2H), 8.45 (br s, 1H ); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 14.1, 61.0, 63.9, 76.9, 92.7, 127.5, 128.8, 132.5, 134.3, 165.9, 171.5, 208.0.

本実施例では、Ｎ'−（１−フェニルヘキサ−５−イン−３−イル）ベンゾヒドラジド（化合物６ａ）を合成した。
プロピオンアルデヒドベンゾイルヒドラゾン（化合物４a、1.0 mmol）のＤＭＦ(10 ml) 溶液に１０℃でＮ，Ｎ−ジイソプロピルエチルアミン（1.5 mmol）と合成例３で調製した化合物３のエーテル溶液（1.5 mmol、濃度はＮＭＲで決定）を滴下した。２４時間攪拌後トリエチルアミン(7.5 mmol) のメタノール溶液を滴下して反応を停止した。さらに３０分間攪拌し、室温まで昇温、水を加えた後、塩化メチレンで３回抽出した。有機相を併せて飽和食塩水で洗浄し、無水硫酸ナトリウム上で乾燥した。乾燥剤を濾別後、減圧濃縮し、得られた残渣を調製用薄層クロマトグラフィー（展開液：ヘキサン／酢酸エチル）で精製して化合物６ａを収率８５％で得た。生成物の物性データを以下に示す。
N'-(1-phenylhex-5-yn-3-yl)benzohydrazide(化合物6a)(表２, entry 1): ¹H NMR (CDCl₃): δ 1.79-2.02 (m, 3H), 2.08 (t, J = 2.7 Hz, 1H), 2.26-2.49 (m, 2H), 2.65-2.89 (m, 2H), 3.29 (tt, J = 5.4 Hz, J = 11.7 Hz, 1H), 7.11-7.24 (m, 5H), 7.31-7.55 (m, 3H), 7.65-7.85 (m, 3H); ¹³C NMR (CDCl₃): ( 29.0, 29.9, 32.1, 58.5, 71.2, 80.8, 126.2, 127.8, 128.1, 128.6, 129.0, 132.9, 134.9, 141.2, 166.7; IR (neat): 3290, 2926, 2118, 1705, 1644, 1451, 880, 698 cm^-1; HRMS (ESI) calcd. for C₁₉H₂₀N_2O [M+H]⁺: m/z 292.1576, found: m/z 292.1575. In this example, N ′-(1-phenylhex-5-in-3-yl) benzohydrazide (Compound 6a) was synthesized.
A solution of propionaldehyde benzoylhydrazone (compound 4a, 1.0 mmol) in DMF (10 ml) at 10 ° C. with N, N-diisopropylethylamine (1.5 mmol) and an ether solution of compound 3 prepared in Synthesis Example 3 (1.5 mmol, concentration: (Determined by NMR) was added dropwise. After stirring for 24 hours, a methanol solution of triethylamine (7.5 mmol) was added dropwise to stop the reaction. The mixture was further stirred for 30 minutes, warmed to room temperature, added with water, and extracted three times with methylene chloride. The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The desiccant was filtered off and concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (developing solution: hexane / ethyl acetate) to obtain Compound 6a in a yield of 85%. The physical property data of the product is shown below.
N '-(1-phenylhex-5-yn-3-yl) benzohydrazide (Compound 6a) (Table 2, entry 1): ¹ H NMR (CDCl ₃ ): δ 1.79-2.02 (m, 3H), 2.08 (t , J = 2.7 Hz, 1H), 2.26-2.49 (m, 2H), 2.65-2.89 (m, 2H), 3.29 (tt, J = 5.4 Hz, J = 11.7 Hz, 1H), 7.11-7.24 (m, 5H), 7.31-7.55 (m, 3H), 7.65-7.85 (m, 3H); ¹³ C NMR (CDCl ₃ ): (29.0, 29.9, 32.1, 58.5, 71.2, 80.8, 126.2, 127.8, 128.1, 128.6, 129.0, 132.9, 134.9, 141.2, 166.7; IR (neat): 3290, 2926, 2118, 1705, 1644, 1451, 880, 698 cm ^-1 ; HRMS (ESI) calcd.for C ₁₉ H ₂₀ N _2O [M + H] ⁺ : m / z 292.1576, found: m / z 292.1575.

次に、この反応の基質に対する依存性を調べた。その結果を表２に示す。

Next, the dependence of this reaction on the substrate was examined. The results are shown in Table 2.

種々のヒドラゾン（化合物４ａ−ｊ）とアレニルトリクロロシラン（化合物３）との反応の結果、収率はプロパギルシラン（化合物２）を用いた反応に比べると若干低下した。芳香族ヒドラゾン（化合物４ｂ、４ｃ）及びα、β−不飽和体（化合物４ｊ）、α−ヒドラゾノエステル（化合物４ｊ）からは、良好な選択性で対応するＮ−アシル−Ｎ’−ホモプロパギルヒドラジン（化合物６）が７０〜７６％で得られた(表２, entry 2,3,5,10)。脂肪族の基質（化合物４ｆ-４ｉ）も化合物３と円滑に反応して目的物（化合物６ｆ−６ｉ）が５８〜６９％で得られた（entry 6-9）。
この場合もほとんどの場合、位置選択性は完璧であり、芳香族ヒドラゾン（化合物４ｂ−４ｄ）を用いた場合のみ僅かにアレニル体が検出された(entry 2-4)。 As a result of the reaction between various hydrazones (compounds 4a-j) and allenyltrichlorosilane (compound 3), the yield was slightly reduced compared to the reaction using propargylsilane (compound 2). From the aromatic hydrazone (compounds 4b and 4c) and the α, β-unsaturated compound (compound 4j) and α-hydrazonoester (compound 4j), the corresponding N-acyl-N′-homopropan is obtained with good selectivity. Gilhydrazine (compound 6) was obtained in 70-76% (Table 2, entry 2,3,5,10). The aliphatic substrate (compound 4f-4i) also reacted smoothly with compound 3 to give the desired product (compound 6f-6i) in 58 to 69% (entry 6-9).
In this case as well, regioselectivity was perfect in most cases, and only a few allenyls were detected only when aromatic hydrazone (compound 4b-4d) was used (entry 2-4).

以下、得られた化合物６ｂ〜６ｊの物性データを示す。
N'-(1-Phenylbut-3-ynyl)benzohydrazide (6b):
(表２, entry 2; R = Ph)
¹H NMR (CDCl₃, 400 MHz): δ 1.87 (t, J = 2.5 Hz, 1H), 2.41-2.75 (m, 3H), 4.01-4.13 (m, 1H), 7.05-7.18 (m, 5H), 7.39-7.59 (m, 3H), 7.76-7.92 (m, 2H), 8.22 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 25.9, 58.7, 70.5, 87.2, 126.9, 127.0, 127.7, 128.5, 128.9, 132.2, 134.4, 143.3, 165.9.
N'-(1-(4-Chlorophenyl)but-3-ynyl)benzohydrazide (6c):
(表２, entry 3; R = 4-ClC₆H₄)
¹H NMR (CDCl₃, 400 MHz): δ 1.95 (t, J = 2.4 Hz, 1H), 2.43-2.65 (m, 2H), 2.96 (br s, 1H), 4.21 (tt, J = 5.1 Hz, J = 11.4 Hz, 1H), 7.02 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 9.0 Hz, 2H), 7.34-7.55 (m, 3H), 7.80-8.05 (m, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ 25.9, 58.6, 69.9, 87.0, 127.5, 128.5, 128.9, 132.1, 132.4, 134.5, 141.9, 165.8.
N'-(1-(4-Methoxyphenyl)but-3-ynyl)benzohydrazide (6d):
(表２, entry 4; R = 4-MeOC₆H₄)
¹H NMR (CDCl₃, 400 MHz): δ 1.92 (t, J = 2.4 Hz, 1H), 2.40-2.77 (m, 3H), 3.97-4.11 (m, 1H), 3.76 (s, 3H), 6.70 (t, J = 8.9 Hz, 2H), 7.03 (t, J = 8.9 Hz, 2H), 7.39-7.56 (m, 3H), 7.70-7.91 (m, 2H), 8.29 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 25.9, 56.3, 58.7, 69.8, 87.1, 114.4, 127.6, 128.1, 128.9, 132.2, 134.1, 135.4, 158.7, 165.6.
N'-((E)-1-Phenylhex-1-en-5-yn-3-yl)benzohydrazide (6e):
(表２, entry 5; R = (E)-PhCH=CH)
¹H NMR (CDCl₃, 400 MHz): δ 1.88 (t, J = 2.5 Hz, 1H), 2.16-2.60 (m, 3H), 3.25-3.37 (m, 1H), 6.07-6-11 (m, 1H), 6.42-6.48 (m, 1H), 7.14-7.30 (m, 5H), 7.45-7.67 (m, 3H), 7.72-7.92 (m, 2H), 8.09 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 27.0, 58.1, 69.9, 86.9, 126.3, 127.5, 128.2, 128.6, 128.9, 129.2, 129.5, 132.0, 134.5, 135.3, 165.7.
N'-(Hept-1-yn-4-yl)benzohydrazide (6f):
(表２, entry 6; R = ⁿPr)
¹H NMR (CDCl₃, 400 MHz): δ 0.90-1.02 (m, 3H), 1.30-1.54 (m, 4H), 1.84 (t, J = 2.5 Hz, 1H), 2.10-2.39 (m, 2H), 2.49-2.70 (m, 2H), 7.31-7.55 (m, 3H), 7.65-7.85 (m, 2H), 8.09 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 14.3, 16.9, 31.8, 34.5, 55.2, 69.4, 83.9, 127.7, 128.9, 132.2, 134.0, 165.6.
N'-(2-Methylhex-5-yn-3-yl)benzohydrazide (6g):
(表２, entry 7; R = ⁱPr)
¹H NMR (CDCl₃, 400 MHz): δ 1.01 (d, J = 7.4 Hz, 6H), 1.85 (t, J = 2.4 Hz, 1H), 2.00-2.11 (m, 1H), 2.17-2.68 (m, 4H), 7.37-7.52 (m, 3H), 7.69-7.90 (m, 2H), 8.17 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 17.0, 28.9, 30.8, 62.3, 69.4, 84.7, 127.5, 128.8, 132.0, 134.3, 165.9.
N'-(1-Cyclohexylbut-3-ynyl)benzohydrazide (6h):
(表２, entry 8; R = Cy)
¹H NMR (CDCl₃, 400 MHz): δ 1.30-1.53 (m, 10H), 1.65-1.72 (m, 1H), 1.89 (t, J = 2.6 Hz, 1H), 2.29-2.76 (m, 3H), 2.79-2.86 (m, 1H), 7.37-7.57 (m, 3H), 7.69-8.05 (m, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ 26.0, 27.5, 28.4, 29.7, 39.0, 58.5, 69.2, 83.8, 127.6, 128.5, 132.6, 134.2, 165.7.
N'-(2,2-Dimethylhex-5-yn-3-yl)benzohydrazide (6i):
(表２, entry 9; R = ^tBu)
¹H NMR (CDCl₃, 400 MHz): δ 1.07 (s, 9H), 1.90 (t, J = 2.5 Hz, 1H), 2.15-2.69 (m, 4H), 7.38-7.59 (m, 3H), 7.66-7.90 (m, 2H), 8.25 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 23.9, 27.5, 33.0, 69.7, 70.9, 84.6, 127.6, 128.9, 132.1, 134.2, 166.0.
Ethyl 2-(Benzamido)pent-4-ynoate (6j):
(表２, entry 10; R = CO₂Et)
¹H NMR (CDCl₃, 400 MHz): δ 1.32 (t, J = 7.2 Hz, 3H), 1.85 (t, J = 2.5 Hz, 1H), 2.00 (br s, 1H), 2.48-2.79 (m, 3H), 3.80-3.89 (m, 1H), 4.15 (q, J = 7.2 Hz, 2H), 7.34-7.61 (m, 3H), 7.75-7.90 (m, 2H), 8.19 (br s, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ 14.0, 22.7, 61.5, 61.9, 70.9, 87.4, 127.6, 129.0, 132.1, 134.4, 166.1, 172.5.
Hereinafter, physical property data of the obtained compounds 6b to 6j are shown.
N '-(1-Phenylbut-3-ynyl) benzohydrazide (6b):
(Table 2, entry 2; R = Ph)
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.87 (t, J = 2.5 Hz, 1H), 2.41-2.75 (m, 3H), 4.01-4.13 (m, 1H), 7.05-7.18 (m, 5H) , 7.39-7.59 (m, 3H), 7.76-7.92 (m, 2H), 8.22 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 25.9, 58.7, 70.5, 87.2, 126.9, 127.0 , 127.7, 128.5, 128.9, 132.2, 134.4, 143.3, 165.9.
N '-(1- (4-Chlorophenyl) but-3-ynyl) benzohydrazide (6c):
(Table 2, entry 3; R = 4-ClC ₆ H ₄ )
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.95 (t, J = 2.4 Hz, 1H), 2.43-2.65 (m, 2H), 2.96 (br s, 1H), 4.21 (tt, J = 5.1 Hz, J = 11.4 Hz, 1H), 7.02 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 9.0 Hz, 2H), 7.34-7.55 (m, 3H), 7.80-8.05 (m, 3H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 25.9, 58.6, 69.9, 87.0, 127.5, 128.5, 128.9, 132.1, 132.4, 134.5, 141.9, 165.8.
N '-(1- (4-Methoxyphenyl) but-3-ynyl) benzohydrazide (6d):
(Table 2, entry 4; R = 4-MeOC ₆ H ₄ )
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.92 (t, J = 2.4 Hz, 1H), 2.40-2.77 (m, 3H), 3.97-4.11 (m, 1H), 3.76 (s, 3H), 6.70 (t, J = 8.9 Hz, 2H), 7.03 (t, J = 8.9 Hz, 2H), 7.39-7.56 (m, 3H), 7.70-7.91 (m, 2H), 8.29 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 25.9, 56.3, 58.7, 69.8, 87.1, 114.4, 127.6, 128.1, 128.9, 132.2, 134.1, 135.4, 158.7, 165.6.
N '-((E) -1-Phenylhex-1-en-5-yn-3-yl) benzohydrazide (6e):
(Table 2, entry 5; R = (E) -PhCH = CH)
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.88 (t, J = 2.5 Hz, 1H), 2.16-2.60 (m, 3H), 3.25-3.37 (m, 1H), 6.07-6-11 (m, 1H), 6.42-6.48 (m, 1H), 7.14-7.30 (m, 5H), 7.45-7.67 (m, 3H), 7.72-7.92 (m, 2H), 8.09 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 27.0, 58.1, 69.9, 86.9, 126.3, 127.5, 128.2, 128.6, 128.9, 129.2, 129.5, 132.0, 134.5, 135.3, 165.7.
N '-(Hept-1-yn-4-yl) benzohydrazide (6f):
(Table 2, entry 6; R = ⁿ Pr)
¹ H NMR (CDCl ₃ , 400 MHz): δ 0.90-1.02 (m, 3H), 1.30-1.54 (m, 4H), 1.84 (t, J = 2.5 Hz, 1H), 2.10-2.39 (m, 2H) , 2.49-2.70 (m, 2H), 7.31-7.55 (m, 3H), 7.65-7.85 (m, 2H), 8.09 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 14.3, 16.9, 31.8, 34.5, 55.2, 69.4, 83.9, 127.7, 128.9, 132.2, 134.0, 165.6.
N '-(2-Methylhex-5-yn-3-yl) benzohydrazide (6g):
(Table 2, entry 7; R = ⁱ Pr)
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.01 (d, J = 7.4 Hz, 6H), 1.85 (t, J = 2.4 Hz, 1H), 2.00-2.11 (m, 1H), 2.17-2.68 (m , 4H), 7.37-7.52 (m, 3H), 7.69-7.90 (m, 2H), 8.17 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 17.0, 28.9, 30.8, 62.3, 69.4, 84.7, 127.5, 128.8, 132.0, 134.3, 165.9.
N '-(1-Cyclohexylbut-3-ynyl) benzohydrazide (6h):
(Table 2, entry 8; R = Cy)
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.30-1.53 (m, 10H), 1.65-1.72 (m, 1H), 1.89 (t, J = 2.6 Hz, 1H), 2.29-2.76 (m, 3H) , 2.79-2.86 (m, 1H), 7.37-7.57 (m, 3H), 7.69-8.05 (m, 3H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 26.0, 27.5, 28.4, 29.7, 39.0, 58.5, 69.2, 83.8, 127.6, 128.5, 132.6, 134.2, 165.7.
N '-(2,2-Dimethylhex-5-yn-3-yl) benzohydrazide (6i):
(Table 2, entry 9; R = ^t Bu)
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.07 (s, 9H), 1.90 (t, J = 2.5 Hz, 1H), 2.15-2.69 (m, 4H), 7.38-7.59 (m, 3H), 7.66 -7.90 (m, 2H), 8.25 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 23.9, 27.5, 33.0, 69.7, 70.9, 84.6, 127.6, 128.9, 132.1, 134.2, 166.0.
Ethyl 2- (Benzamido) pent-4-ynoate (6j):
(Table 2, entry 10; R = CO ₂ Et)
¹ H NMR (CDCl ₃ , 400 MHz): δ 1.32 (t, J = 7.2 Hz, 3H), 1.85 (t, J = 2.5 Hz, 1H), 2.00 (br s, 1H), 2.48-2.79 (m, 3H), 3.80-3.89 (m, 1H), 4.15 (q, J = 7.2 Hz, 2H), 7.34-7.61 (m, 3H), 7.75-7.90 (m, 2H), 8.19 (br s, 1H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ 14.0, 22.7, 61.5, 61.9, 70.9, 87.4, 127.6, 129.0, 132.1, 134.4, 166.1, 172.5.

本発明の方法により製造されるＮ−アシルヒドラジン及びそれらから誘導されるアミン化合物はピロリジン誘導体の原料になるなど（Org. Lett. 2001, 3, 511-514）、医薬品などファインケミカルズの合成中間体として有用である。 N-acylhydrazines produced by the method of the present invention and amine compounds derived therefrom are used as raw materials for pyrrolidine derivatives (Org. Lett. 2001, 3, 511-514), and as synthetic intermediates for fine chemicals such as pharmaceuticals. Useful.

Claims

The following general formula 1: R ¹ HC═NNHCOR ²
(In the formula, R ¹ represents a hydrocarbon group or a heterocyclic group which may have a substituent, and R ² represents an aromatic hydrocarbon which may have a substituent.)
N-acylhydrazone represented by the following general formula 2: CH≡C—CH ₂ —SiX ₃
(Wherein X represents a halogen atom) or propargyltrihalosilane represented by the formula: CH ₂ ═C═CH—SiX ₃
(Wherein X represents a halogen atom) The following general formula 4 consisting of reacting with an allenyltrihalosilane represented by: CH ₂ ═C═CH—CHR ¹ —NH—NHCOR ²
Or Chemical Formula 5: CH≡C—CH ₂ —CHR ¹ —NH—NHCOR ²
(Wherein R ^{1 and} R ² are defined in the same manner as described above).

The process according to claim 1 , wherein dimethylformamide is used as a reaction solvent.

The process according to claim 1 or 2 , wherein a tertiary amine is further added to the reaction system.

A process for producing allenylmethylamine or homopropargylamine comprising reacting the N-acylhydrazine produced by the process according to any one of claims 1 to 3 with samarium iodide.

The allenylmethylamine is represented by the following formula 6: CH ₂ ═C═CH—CHR ¹ —NH ₂
The homopropargylamine is represented by the following formula 7: CH≡C—CH ₂ —CHR ¹ —NH ₂
(In the formula, R ¹ is as defined above.) A process according to claim 4 which is represented by.