JP2004262863A - Method for producing orthobenzidine compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing an orthobenzidine compound which is difficult to produce by traditional producing methods, readily and in a high yield. <P>SOLUTION: Ortho-benzidine compounds with a specific structure is synthesized by making a hydrazobenzene compound with a specific structure carry out a rearrangement reaction in the presence of a reaction agent showing an aprotic Lewis acidic property. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

【００１２】
【外４】

【００１３】
（式（１）、（２）中、Ｒ^１、Ｒ^２は、それぞれ独立に、置換または無置換のアルキル基、置換または無置換のアルコキシ基、置換または無置換のアラルキル基、置換または無置換のアリール基、または、ハロゲン原子を示す。Ｒ^３、Ｒ^４は、それぞれ、水素原子を示す。ただし、Ｒ^１とＲ^３とは、結合して芳香環を形成してもよく、Ｒ^２とＲ^４とは、結合して芳香環を形成してもよい。）
本発明によれば、窒素原子のパラ位に置換基を有するオルトベンジジン化合物が高選択的、かつ高収率で得られる。反応機構は明確ではないが、非プロトン性のルイス酸性を示す反応剤の中心原子（金属原子、リン原子、ケイ素原子など）に、上記式（１）で示される構造のヒドラゾベンゼン化合物の２つ窒素原子の孤立電子対が配位し、歪みの大きな３員環構造を含む中間体を形成した後、より安定した構造になるために転位反応を起こし、オルト位での結合を形成したオルトベンジジン化合物が生成するものと考えている。
【００１４】
【発明の実施の形態】
上記式（１）、（２）中Ｒ^１、Ｒ^２のアルキル基としては、メチル基、エチル基、ｎ−プロピル基、ｔ−ブチル基などが挙げられ、アルコキシ基としては、メトキシ基、エトキシ基、プロポキシ基などが挙げられ、アラルキル基としては、ベンジル基、フェネチル基などが挙げられ、アリール基としては、フェニル基、ナフチル基などが挙げられ、ハロゲン原子としては、フッ素原子、塩素原子、臭素原子などが挙げられる。
【００１５】
また、上記各基が有してもよい置換基としては、メチル、エチル基などのアルキル基や、メトキシ、エトキシなどのアルコキシ基や、ニトロ基や、シアノ基や、フッ素原子、塩素原子、臭素原子などのハロゲン原子が挙げられる。
【００１６】
以下に、上記式（１）で示される構造の４−，４’−位に置換基を有するヒドラゾベンゼン化合物の具体例を示すが、本発明はこれら具体例に限定されるものではない。
【００１７】
【外５】

【００１８】
【外６】

【００１９】
次に、上記式（２）で示される構造のオルトベンジジン化合物の具体例を示すが、本発明はこれら具体例に限定されるものではない。
【００２０】
【外７】

【００２１】
【外８】

【００２２】
本発明の製造法において用いられる反応剤は、非プロトン性のルイス酸性を示すものであればよく、特には、その構造中に、金属原子、リン原子またはケイ素原子を含む反応剤が好ましい。そのような反応剤としては、例えば、三塩化アルミニウム、三臭化アルミニウム、三塩化リン、三臭化リン、三塩化鉄、三臭化鉄、トリメチルシリルクロリド、トリ−ｔｅｒｔ−ブチルスズなどが挙げられる。
【００２３】
また、非プロトン性のルイス酸性を示す反応剤の使用量は、出発物質である上記式（１）で示される構造の４−，４’−位に置換基を有するヒドラゾベンゼン化合物に対して、０．０１〜１０当量であることが好ましく、０．０５〜５当量であることがより好ましく、０．１〜２当量であることがより一層好ましい。
【００２４】
本発明の製造法に用いられる溶媒については、特に限定はないが、トルエン、ヘキサン、アセトニトリル、ジメチルホルムアミド、ジメチルスルホキシド、ジクロルメタン、クロロホルムなどの非プロトン性溶媒が好ましい。
【００２５】
反応温度に関しては、ハンドリングの点で、−１００〜１５０℃の範囲で行うことが好ましく、１０〜５０℃の範囲で反応を行うことがより好ましい。
【００２６】
本発明の製造法は、常圧下、空気中で製造することができる方法であるが、窒素あるいはアルゴンといった不活性ガス化下で製造を行ってもよい。
【００２７】
反応終了後、常法で処理することにより目的の化合物を得ることができる。
【００２８】
上記式（１）で示される構造の４−，４’−位に置換基を有するヒドラゾベンゼン化合物は、例えば、所望の置換基をパラ位に有するニトロベンゼン誘導体を原料として、エタノール溶媒中で、水酸化ナトリウム水溶液、水酸化カリウム水溶液、亜鉛、アルミニウムなどの触媒存在下で反応させることで、収率良く得ることができる。
【００２９】
上記式（１）で示される構造の４−，４’−位に置換基を有するヒドラゾベンゼン化合物の合成例を以下に示す。
【００３０】
（合成例１）
・上記式（１−１）で示される構造のヒドラゾベンゼン化合物（ヒドラゾトルエン）の合成
４−ニトロトルエン（１３．０ｇ／９４．８ｍｍｏｌ）を３００ｍｌフラスコ中、エタノール（１００ｍｌ）に溶解し、さらに水酸化ナトリウム水溶液（水酸化ナトリウム１６．６ｇと水４０ｍｌ）を加えて攪拌した。その後、亜鉛（１５．２ｇ／０．２２ｍｏｌ）を加え、超音波により脱気した。その後、超音波に掛けながら４時間還流した。その後、室温まで冷却し、さらに亜鉛（２５．０ｇ／０．３６ｍｏｌ）、エタノール（９０ｍｌ）、水酸化ナトリウム水溶液（水酸化ナトリウム１６．６ｇと水４０ｍｌ）を加え、再び超音波に掛けながら２時間還流した。
【００３１】
反応溶液を吸引濾過し、濾液に含まれるヒドラゾトルエンを熱したベンゼンで抽出した。ベンゼンを除去し、ヒドラゾトルエン（６．２３ｇ／２９．４ｍｍｏｌ）を得た。
【００３２】
・ヒドラゾトルエン
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３／ＴＭＳ）δ＝１．２６（２Ｈ，ｓ），２．４２（６Ｈ，ｓ），７．３０（４Ｈ，ｄ，Ｊ＝８．９Ｈｚ），７．８１（４Ｈ，ｄ，Ｊ＝８．９Ｈｚ）
ＩＲ：（ＫＢｒ）ν＝３３３４，３０４９，３０２１，２９５８，２８６９，１６０３，１５０５，７４９ｃｍ^−１
ｍ．ｐ．：１２３．０〜１２６．７℃
収率：６５％
（合成例２）
・上記式（１−３）で示される構造のヒドラゾベンゼン化合物（ヒドラゾアニソール）の合成
・上記式（１−６）で示される構造のヒドラゾベンゼン化合物（４，４’−ジブロモヒドラゾベンゼン）の合成
・上記式（１−７）で示される構造のヒドラゾベンゼン化合物（４−メトキシ−４’−ブロモヒドラゾベンゼン）の合成
４−ニトロアニソール（８．０ｇ／０．５２ｍｍｏｌ）と４−ブロモニトロベンゼン（１０．６ｇ／０．５２ｍｍｏｌ）を３００ｍｌフラスコ中、エタノール（１００ｍｌ）に溶解し、さらに水酸化ナトリウム水溶液（水酸化ナトリウム１６．６ｇと水４０ｍｌ）を加え攪拌した。その後、アルミニウム（１５．２ｇ０．２２ｍｏｌ）を加え、超音波により脱気した。その後、超音波に掛けながら４時間還流した。その後、室温まで冷却し、さらにアルミニウム（２５．０ｇ／０．３６ｍｏｌ），エタノール（９０ｍｌ），水酸化ナトリウム水溶液（水酸化ナトリウム１６．６ｇと水４０ｍｌ）を加え、再び超音波に掛けながら２時間還流した。
【００３３】
反応溶液を吸引濾過し、濾液に含まれるヒドラゾトルエンを熱したベンゼンで抽出した。ベンゼンを除去し、カラムクロマトグラフィー（ＳｉＯ_２、１００倍、ヘキサン：酢酸エチル＝９：１）により精製し、ヒドラゾアニソール、４，４’−ジブロモヒドラゾベンゼン、４−メトキシ−４’−ブロモヒドラゾベンゼンを１：１：２の割合で得た。
【００３４】
・ヒドラゾアニソール
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３／ＴＭＳ）δ＝１．１８（２Ｈ，ｓ），３．８０（６Ｈ，ｓ），６．９２（４Ｈ，ｄ，Ｊ＝８．９Ｈｚ），７．８０（４Ｈ，ｄ，Ｊ＝８．９Ｈｚ）
ＩＲ：（ＫＢｒ）ν＝３３０１，３０８４，３０３４，３０１４，２９５２，２８３５，１６０８，１５０３，１２３６，１０３１，８０６ｃｍ^−１
ｍ．ｐ．：１９９．５〜２０２．６℃
収率：２２％
・４，４’−ジブロモヒドラゾベンゼン
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３／ＴＭＳ）δ＝４．８４（２Ｈ，ｓ），６．７２（４Ｈ，ｄ，Ｊ＝８．９Ｈｚ），７．３４（４Ｈ，ｄ，Ｊ＝８．９Ｈｚ）
ＩＲ：（ＫＢｒ）ν＝３２４１，３０７０，１５９１，１０６９，８２３，８０９ｃｍ^−１
収率：２３％
・４−メトキシ−４’−ブロモヒドラゾベンゼン
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３／ＴＭＳ）δ＝３．７７（３Ｈ，ｓ），４．６６（２Ｈ，ｂｓ）６．７〜６．８（６Ｈ，ｍ，），７．３３（２Ｈ，ｍ）
ＩＲ：（ＫＢｒ）ν＝３３３０，２９５４，２８３５，１５８８，１２３０，１０７０，１０３３，８２４ｃｍ^−１
ｍ．ｐ．２２５．２〜２２８．１℃
収率：４６％
その他の上記式（１）で示される構造の４−，４’−位に置換基を有するヒドラゾベンゼン化合物も、合成例１、２と同様にして合成できる。
【００３５】
【実施例】
以下に、上記式（１）で示される構造の４−，４’−位に置換基を有するヒドラゾベンゼン化合物から上記式（２）で示される構造のオルトベンジジン化合物を合成する実施例を示すが、本発明はこれら実施例に限定されるものではない。
【００３６】
（実施例１）
・上記式（２−１）で示される構造のオルトベンジジン化合物（４，４’−ジメチルオルトベンジジン）の合成
上記式（１−１）で示される構造のヒドラゾベンゼン化合物（ヒドラゾトルエン）２．０ｇ（９．４２ｍｍｏｌ）を１００ｍｌフラスコ中、アルゴン置換し、ヘキサン５０ｍｌ（溶媒）に溶解し、攪拌した。そこに、非プロトン性のルイス酸性を示す反応剤としてＰＢｒ_３（３．７７ｍｍｏｌ／ｍｌ：０．４当量）を滴下し、１日攪拌した。その後、溶媒を除去し、炭酸水素ナトリウム水溶液でクエンチ、ジエチルエーテルで抽出をした。その後、抽出溶媒を除去し、カラムクロマトグラフィー（ＳｉＯ_２、１００倍、ヘキサン：酢酸エチル＝９：１）により精製し、上記式（２−１）で示される構造のオルトベンジジン化合物（４，４’−ジメチルオルトベンジジン）を得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３／ＴＭＳ）δ＝１．２５（２Ｈ，ｓ），２．６４（６Ｈ，ｓ），７．６６（２Ｈ，ｄ， Ｊ＝８．９Ｈｚ），７．９７（２Ｈ，ｓ），８．１１（２Ｈ，ｄ，Ｊ＝８．９Ｈｚ）
ＩＲ：（ＫＢｒ）ν＝３４３５，３０５１，２９２４，２８５３，１６３８，１５１４，１３５６，８０３ｃｍ^−１
ｍ．ｐ．：２４２．１〜２４５．９℃
収率：７１％
（実施例２〜１１）
実施例１において、出発原料を表１に示すヒドラゾベンゼン化合物に変更した以外は、実施例１と同様にして、表１に示すオルトベンジジン化合物を合成した。
【００３７】
（実施例１２〜１６）
実施例１において、非プロトン性のルイス酸性を示す反応剤の種類・量および溶媒を表１に示すとおりに変更した以外は、それぞれ実施例１と同様にして、表１に示すオルトベンジジン化合物を合成した。
【００３８】
実施例１〜１６の結果を表１に示す。
【００３９】
【表１】

【００４０】
（比較例１）
実施例１において、非プロトン性のルイス酸性を示す反応剤であるＰＢｒ_３を、プロトン性の酸である塩酸に変更した以外は、実施例１と同様にして反応させた。しかし、目的化合物である上記式（２−１）で示される構造のオルトベンジジン化合物（４，４’−ジメチルオルトベンジジン）は全く得られなかった。
【００４１】
（比較例２）
３，３’−ジメチルビフェニル３．６ｇ（１９．８ｍｍｏｌ）、ヨウ素４．０ｇ（３１．６ｍｍｏｌ）、過ヨウ素酸１．８ｇ（７．９ｍｍｏｌ）、氷酢酸２０ｍｌ、水５ｍｌを、ジムロート型冷却管、温度計、攪拌機を装着した１００ｍｌ三つ口フラスコに入れ、８０℃で２時間過熱攪拌した。
【００４２】
反応終了後、生成物をトルエンで抽出した後、有機層を１０％チオ硫酸ナトリウム水溶液、１０％炭酸水素ナトリウム水溶液、水の順で、有機層を洗浄した。
【００４３】
その後、トルエンを留去し、カラムクロマトグラフィーを用いて、精製を行い、３，３’−ジメチル−６，６’−ヨードビフェニル１．２ｇ（収率１４．０％）を得た。
【００４４】
次に、３，３’−ジメチル−６，６’−ヨードビフェニル１．２ｇ（２．７６ｍｍｏｌ）、アセトアミド０．３３ｇ（５．５２ｍｍｏｌ）、銅紛０．８８ｇ（１３．８ｍｍｏｌ）、炭酸カリウム０．７６ｇ（５．５２ｍｍｏｌ）およびオルトジクロロベンゼン１０ｍｌを入れ、オイルバスにて、８時間加熱還流を行った（Ｕｌｌｍａｎｎ反応）。
【００４５】
放冷後、トルエン２０ｍｌを加えた後、濾過で触媒を除いた。
【００４６】
さらに、得られた粗反応物にナトリウムメチキシドを加え、２時間加熱還流を行った。反応液を水に注いだ後、トルエンで抽出し、有機層を水洗した。その後、有機層を分取し、トルエンを濃縮した後、カラムクロマトグラフィーを用いて、目的物を分取し、上記式（２−１）で示される構造のオルトベンジジン化合物（４，４’−ジメチルオルトベンジジン）０．１ｇを得た（収率１７．１％）。
【００４７】
実施例ではいずれの場合も、上記式（２）で示される構造のオルトベンジジン化合物が収率良く得られているが、従来の方法（比較例１：ベンジジン転位法、比較例２：Ｕｌｌｍａｎｎ反応による合成法）を使用した場合には、目的物が全く得られない、または、収率が極めて低いという結果であった。
【００４８】
以上のことから、本発明の有用性は明らかである。
【００４９】
【発明の効果】
本発明によれば、従来の製造法では合成が困難であったオルトベンジジン化合物を、容易かつ高収率で製造することができる。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing an orthobenzidine compound having a specific structure.
[0002]
The orthobenzidine compound having a specific structure produced by the production method of the present invention is a pharmaceutical, an intermediate for agricultural chemicals, an intermediate for dyes such as organic dyes and organic pigments, a catalyst for asymmetric synthesis, or an organic electroluminescent material. It is useful as an intermediate of an organic photoconductive material of an organic electrophotographic photosensitive member in electrophotography.
[0003]
[Prior art]
As a method for synthesizing a benzidine compound from a hydrazobenzene compound, a method using a benzidine rearrangement in which a hydrazobenzene compound is subjected to a rearrangement reaction in the presence of a protonic acid such as hydrochloric acid (see Non-Patent Document 1) is known.
[0004]
However, according to this method, although a parabenzidine compound is obtained, an orthobenzidine compound is not obtained at all, or even a very small amount is obtained. In addition, the above-mentioned benzidine rearrangement using a protonic acid as a catalyst is carried out using a hydrazobenzene compound having a substituent introduced at the 4-, 4'-position (para position of a nitrogen atom) as a bond position of the benzidine rearrangement as a starting material. Even if it is applied, only a semizine compound in which a C—N bond is newly generated or an azo compound in which a hydrazobenzene compound is decomposed is generated, and an orthobenzidine compound as an object compound of the present invention is not obtained at all.
[0005]
Other methods for obtaining an orthobenzidine compound include a method using a Suzuki reaction (Non-patent Document 2) for coupling an arylboronic acid compound and an aryl halide compound, and a method using a copper catalyst as an iodinated aryl compound. A method of applying a coupling reaction to obtain a biphenyl compound, such as the Ullmann reaction (Non-patent Document 3), which is heated at a high temperature in the presence of the compound, is also conceivable. In the case of synthesizing a compound, an orthobenzidine compound cannot be obtained because an arylamine in which an amino group has reacted is generated.
[0006]
Furthermore, a method of applying the above-described coupling reaction to obtain a nitro compound or a phenol compound which can be a precursor compound of an orthobenzidine compound and then substituting the nitro compound or a phenol compound with an amino group is also considered. It is difficult to synthesize an aryl boronic acid compound or an aryl halide compound, and the method cannot be practically applied as a synthesis method.
[0007]
Furthermore, there is a method in which an iodine atom is directly introduced into the ortho position of the biphenyl compound, and then an amino group is introduced by using the Ullmann reaction. However, the synthesis yield of the iodine compound used as a raw material is low, and the Ullmann reaction itself is not used. Since the yield is low, the total yield is extremely low, which is not practical.
[0008]
[Non-patent document 1]
Dai Organic Chemistry (Asakura Shoten: Vol. 16, 1959), p. 517-518
[Non-patent document 2]
TCL Mail (Tokyo Chemical Industry Co., Ltd .: 2000/1 No. 105), p. 18-22
[Non-Patent Document 3]
Dai Organic Chemistry (Asakura Shoten: Vol. 16, 1959), p. 510-513
[0009]
[Problems to be solved by the invention]
An object of the present invention is to provide a method for easily producing an orthobenzidine compound, which has been difficult to synthesize by a conventional production method, in a high yield.
[0010]
[Means for Solving the Problems]
According to the present invention, a hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the following formula (1) is subjected to a rearrangement reaction in the presence of an aprotic Lewis acidic reagent. And synthesizing an orthobenzidine compound having a structure represented by the following formula (2).
[0011]
[Outside 3]

[0012]
[Outside 4]

[0013]
(In the formulas (1) and (2), R ¹ and R ² each independently represent a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group or,, ^.R 3, ^{R 4} which represents a halogen atom, respectively, a hydrogen atom. However, ^{R 1} and ^{R 3,} may form an aromatic ring bonded to an ^{R 2} It may combine with R ⁴ to form an aromatic ring.)
According to the present invention, an orthobenzidine compound having a substituent at the para-position of a nitrogen atom can be obtained with high selectivity and high yield. Although the reaction mechanism is not clear, the central atom (metal atom, phosphorus atom, silicon atom, etc.) of the aprotic reagent exhibiting Lewis acidity is added to the hydrazobenzene compound of the structure represented by the above formula (1). After the lone pair of nitrogen atoms coordinate to form an intermediate containing a highly strained three-membered ring structure, a rearrangement reaction takes place to form a more stable structure, and an ortho-form bond is formed. It is believed that a benzidine compound is formed.
[0014]
BEST MODE FOR CARRYING OUT THE INVENTION
In the above formulas (1) and (2), examples of the alkyl group of R ¹ and R ² include a methyl group, an ethyl group, an n-propyl group and a t-butyl group, and examples of the alkoxy group include a methoxy group and an ethoxy group. Groups, propoxy group, etc., as aralkyl group, benzyl group, phenethyl group, etc., as aryl group, phenyl group, naphthyl group, etc., as halogen atom, fluorine atom, chlorine atom, And a bromine atom.
[0015]
Examples of the substituent which each of the above groups may have include alkyl groups such as methyl and ethyl groups, alkoxy groups such as methoxy and ethoxy, nitro groups, cyano groups, fluorine atoms, chlorine atoms, and bromine. And halogen atoms such as atoms.
[0016]
Hereinafter, specific examples of the hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the above formula (1) will be shown, but the present invention is not limited to these specific examples.
[0017]
[Outside 5]

[0018]
[Outside 6]

[0019]
Next, specific examples of the orthobenzidine compound having the structure represented by the above formula (2) are shown, but the present invention is not limited to these specific examples.
[0020]
[Outside 7]

[0021]
[Outside 8]

[0022]
The reactant used in the production method of the present invention only needs to exhibit aprotic Lewis acidity, and in particular, a reactant containing a metal atom, a phosphorus atom or a silicon atom in its structure is preferable. Examples of such a reactant include aluminum trichloride, aluminum tribromide, phosphorus trichloride, phosphorus tribromide, iron trichloride, iron tribromide, trimethylsilyl chloride, tri-tert-butyltin, and the like.
[0023]
The amount of the aprotic Lewis acid reactant used is based on the hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the above formula (1) as a starting material. , 0.01 to 10 equivalents, more preferably 0.05 to 5 equivalents, and even more preferably 0.1 to 2 equivalents.
[0024]
The solvent used in the production method of the present invention is not particularly limited, but an aprotic solvent such as toluene, hexane, acetonitrile, dimethylformamide, dimethylsulfoxide, dichloromethane or chloroform is preferable.
[0025]
The reaction temperature is preferably in the range of -100 to 150C from the viewpoint of handling, and more preferably in the range of 10 to 50C.
[0026]
The production method of the present invention is a method that can be produced in the air under normal pressure, but it may be produced under an inert gas such as nitrogen or argon.
[0027]
After the completion of the reaction, the desired compound can be obtained by treating with a conventional method.
[0028]
The hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the above formula (1) can be obtained, for example, by using a nitrobenzene derivative having a desired substituent at a para position as a raw material in an ethanol solvent. By performing the reaction in the presence of a catalyst such as an aqueous solution of sodium hydroxide, an aqueous solution of potassium hydroxide, zinc, or aluminum, a high yield can be obtained.
[0029]
An example of the synthesis of a hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the above formula (1) will be shown below.
[0030]
(Synthesis example 1)
-Synthesis of hydrazobenzene compound (hydrazotoluene) having the structure represented by the above formula (1-1) 4-Nitrotoluene (13.0 g / 94.8 mmol) was dissolved in ethanol (100 ml) in a 300 ml flask, and further dissolved. An aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) was added and stirred. Thereafter, zinc (15.2 g / 0.22 mol) was added, and the mixture was degassed by ultrasonic waves. Thereafter, the mixture was refluxed for 4 hours while applying ultrasonic waves. Thereafter, the mixture is cooled to room temperature, and zinc (25.0 g / 0.36 mol), ethanol (90 ml), and an aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) are added, and the mixture is again ultrasonicated for 2 hours. Refluxed.
[0031]
The reaction solution was subjected to suction filtration, and hydrazotoluene contained in the filtrate was extracted with hot benzene. The benzene was removed to obtain hydrazotoluene (6.23 g / 29.4 mmol).
[0032]
・ Hydrazotoluene
¹ H-NMR (CDCl _{3 /} TMS) δ = 1.26 (2H, s), 2.42 (6H, s), 7.30 (4H, d, J = 8.9 Hz), 7.81 (4H , D, J = 8.9 Hz)
IR: (KBr) v = 3334,3049,3021,958,2869,1603,1505,749cm- ¹
m. p. : 123.0-126.7 ° C
Yield: 65%
(Synthesis example 2)
-Synthesis of a hydrazobenzene compound (hydrazoanisole) having a structure represented by the above formula (1-3)-A hydrazobenzene compound (4,4'-dibromohydrazo) having a structure represented by the above formula (1-6) Synthesis of hydrazobenzene compound (4-methoxy-4′-bromohydrazobenzene) having a structure represented by the above formula (1-7) 4-nitroanisole (8.0 g / 0.52 mmol) 4-Bromonitrobenzene (10.6 g / 0.52 mmol) was dissolved in ethanol (100 ml) in a 300 ml flask, and an aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water) was added and stirred. Thereafter, aluminum (15.2 g 0.22 mol) was added, and the mixture was degassed by ultrasonic waves. Thereafter, the mixture was refluxed for 4 hours while applying ultrasonic waves. Thereafter, the mixture is cooled to room temperature, further added with aluminum (25.0 g / 0.36 mol), ethanol (90 ml), and an aqueous sodium hydroxide solution (16.6 g of sodium hydroxide and 40 ml of water), and again subjected to ultrasonic waves for 2 hours. Refluxed.
[0033]
The reaction solution was subjected to suction filtration, and hydrazotoluene contained in the filtrate was extracted with hot benzene. The benzene was removed, and the product was purified by column chromatography (SiO ₂ , 100-fold, hexane: ethyl acetate = 9: 1) to obtain hydrazoanisole, 4,4′-dibromohydrazobenzene, 4-methoxy-4′-bromo. The hydrazobenzene was obtained in a ratio of 1: 1: 2.
[0034]
・ Hydrazoanisole
¹ H-NMR (CDCl _{3 /} TMS) δ = 1.18 (2H, s), 3.80 (6H, s), 6.92 (4H, d, J = 8.9 Hz), 7.80 (4H) , D, J = 8.9 Hz)
IR: (KBr) v = 3301, 3084, 3034, 3014, 2952, 2835, 1608, 1503, 1236, 1031, 806 cm ^-1
m. p. 199.5-202.6 ° C
Yield: 22%
・ 4,4′-dibromohydrazobenzene
¹ H-NMR (CDCl _{3 /} TMS) δ = 4.84 (2H, s), 6.72 (4H, d, J = 8.9 Hz), 7.34 (4H, d, J = 8.9 Hz)
IR: (KBr) ν = 3241, 3070, 1591, 1069, 823, 809 cm ⁻¹
Yield: 23%
-4-methoxy-4'-bromohydrazobenzene
¹ H-NMR (CDCl _{3 /} TMS) δ = 3.77 (3H, s), 4.66 (2H, bs) 6.7 to 6.8 (6H, m,), 7.33 (2H, m) )
IR: (KBr) ν = 3330, 2954, 2835, 1588, 1230, 1070, 1033, 824 cm ^-1
m. p. 225.2-228.1 ° C
Yield: 46%
Other hydrazobenzene compounds having a substituent at the 4-, 4'-position of the structure represented by the above formula (1) can be synthesized in the same manner as in Synthesis Examples 1 and 2.
[0035]
【Example】
Hereinafter, an example of synthesizing an orthobenzidine compound having the structure represented by the above formula (2) from a hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the above formula (1) will be described. However, the present invention is not limited to these examples.
[0036]
(Example 1)
-Synthesis of orthobenzidine compound (4,4'-dimethylorthobenzidine) having the structure represented by the above formula (2-1) Hydrazobenzene compound (hydrazotoluene) 2 having the structure represented by the above formula (1-1) In a 100 ml flask, 0.0 g (9.42 mmol) was replaced with argon, dissolved in 50 ml of hexane (solvent), and stirred. Thereto, PBr ₃ (3.77 mmol / ml: 0.4 equivalent) was added dropwise as a reactant exhibiting aprotic Lewis acidity, and the mixture was stirred for one day. Thereafter, the solvent was removed, quenched with an aqueous sodium hydrogen carbonate solution, and extracted with diethyl ether. Thereafter, the extraction solvent was removed, and the product was purified by column chromatography (SiO ₂ , 100 times, hexane: ethyl acetate = 9: 1), and the orthobenzidine compound (4,4) having the structure represented by the above formula (2-1) was obtained. '-Dimethylorthobenzidine).
¹ H-NMR (CDCl _{3 /} TMS) δ = 1.25 (2H, s), 2.64 (6H, s), 7.66 (2H, d, J = 8.9 Hz), 7.97 (2H) , S), 8.11 (2H, d, J = 8.9 Hz)
IR: (KBr) ν = 3435, 3051, 924, 2853, 1638, 1514, 1356, 803 cm ⁻¹
m. p. : 242.1 to 245.9 ° C
Yield: 71%
(Examples 2 to 11)
An orthobenzidine compound shown in Table 1 was synthesized in the same manner as in Example 1 except that the starting material was changed to the hydrazobenzene compound shown in Table 1.
[0037]
(Examples 12 to 16)
In Example 1, the orthobenzidine compound shown in Table 1 was prepared in the same manner as in Example 1 except that the type and amount of the aprotic Lewis acidic reactant and the solvent were changed as shown in Table 1. Synthesized.
[0038]
Table 1 shows the results of Examples 1 to 16.
[0039]
[Table 1]

[0040]
(Comparative Example 1)
The reaction was carried out in the same manner as in Example 1 except that PBr ₃ , which was a reactant exhibiting aprotic Lewis acidity, was changed to hydrochloric acid, which is a protic acid. However, the target compound, an orthobenzidine compound (4,4′-dimethylorthobenzidine) having the structure represented by the above formula (2-1) was not obtained at all.
[0041]
(Comparative Example 2)
3.6 g (19.8 mmol) of 3,3′-dimethylbiphenyl, 4.0 g (31.6 mmol) of iodine, 1.8 g (7.9 mmol) of periodic acid, 20 ml of glacial acetic acid, and 5 ml of water were added to a Dimroth condenser. The mixture was placed in a 100 ml three-necked flask equipped with a thermometer and a stirrer, and stirred at 80 ° C. for 2 hours.
[0042]
After the reaction was completed, the product was extracted with toluene, and the organic layer was washed with a 10% aqueous sodium thiosulfate solution, a 10% aqueous sodium hydrogen carbonate solution and water in this order.
[0043]
Thereafter, toluene was distilled off, and purification was performed using column chromatography to obtain 1.2 g of 3,3′-dimethyl-6,6′-iodobiphenyl (14.0% yield).
[0044]
Next, 1.2 g (2.76 mmol) of 3,3′-dimethyl-6,6′-iodobiphenyl, 0.33 g (5.52 mmol) of acetamide, 0.88 g (13.8 mmol) of copper powder, and 0% of potassium carbonate 0.76 g (5.52 mmol) and 10 ml of orthodichlorobenzene were added, and the mixture was heated and refluxed for 8 hours in an oil bath (Ullmann reaction).
[0045]
After cooling, 20 ml of toluene was added, and the catalyst was removed by filtration.
[0046]
Further, sodium methoxide was added to the obtained crude reaction product, and the mixture was heated under reflux for 2 hours. The reaction solution was poured into water, extracted with toluene, and the organic layer was washed with water. Thereafter, the organic layer was separated, the toluene was concentrated, and then the target product was separated using column chromatography, and the orthobenzidine compound (4,4′-) having a structure represented by the above formula (2-1) was obtained. 0.1 g of dimethyl orthobenzidine) was obtained (yield 17.1%).
[0047]
In each of the examples, the orthobenzidine compound having the structure represented by the above formula (2) was obtained in good yield in all cases, but the conventional methods (Comparative Example 1: Benzidine rearrangement method, Comparative Example 2: Ullmann reaction) In the case of using the synthesis method), the desired product was not obtained at all, or the yield was extremely low.
[0048]
From the above, the usefulness of the present invention is clear.
[0049]
【The invention's effect】
According to the present invention, an orthobenzidine compound, which was difficult to synthesize by a conventional production method, can be produced easily and in a high yield.

Claims (2)

By subjecting a hydrazobenzene compound having a substituent at the 4-, 4'-position of the structure represented by the following formula (1) to a rearrangement reaction in the presence of an aprotic Lewis acidic reactant, the following formula: A method for producing an orthobenzidine compound, comprising synthesizing an orthobenzidine compound having the structure represented by (2).
[Outside 1]

[Outside 2]

(In the formulas (1) and (2), R ¹ and R ² each independently represent a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group or,, ^.R 3, ^{R 4} which represents a halogen atom, respectively, a hydrogen atom. However, ^{R 1} and ^{R 3,} may form an aromatic ring bonded to an ^{R 2} It may combine with R ⁴ to form an aromatic ring.) The method for producing an orthobenzidine compound according to claim 1, wherein the reactant exhibiting aprotic Lewis acidity is a reactant containing at least one atom selected from the group consisting of a metal atom, a phosphorus atom and a silicon atom. Law.