JP3668540B2 - Method for producing ketone - Google Patents

Description

（式中、Ｒ¹ 及びＲ² は、同一又は異なって、アルキル基、アルケニル基、アルキニル基、シクロアルキル基、アラルキル基を示し、Ｒ¹ 及びＲ² は互いに結合して非芳香族環を形成してもよい）
前記式において、Ｒ¹ 及びＲ² で表されるアルキル基には、直鎖状又は分枝鎖状Ｃ_1-20アルキル基（好ましくはＣ_1-10アルキル基）が含まれ、アルケニル基には、例えば、ビニル、１−プロペニル、２−プロペニル、イソプロペニル、ブテニル、ペンテニル基などのＣ_2-10アルケニル基が含まれ、アルキニル基には、例えば、エチニル、プロピニル基などのＣ_2-10アルキニル基が含まれる。
Ｒ¹ 及びＲ² で表されるシクロアルキル基としては、例えば、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチルなどのＣ_3-20シクロアルキル基（好ましくはＣ_4-10シクロアルキル基）が含まれ、アラルキル基には、例えば、ベンジル、フェネチル基などのＣ_6-12アリール−Ｃ_1-4アルキル基などが含まれる。
【００１３】
二級アルコールには、二級ヒドロキシル基を有する一価アルコールや多価アルコールなどが含まれる。二級アルコールのうち一価アルコールには、例えば、２−プロパノール、２−ブタノール、２−ペンタノール、３−ペンタノール、２−ヘキサノール、３−ヘキサノール、２−ヘプタノール、２−オクタノールなどの炭素数１〜２０程度の脂肪族アルコール；シクロペンタノール、シクロヘキサノール、２−メチルシクロヘキサノール、３−メチルシクロヘキサノール、４−メチルシクロヘキサノール、４−ｔ−ブチルシクロヘキサノール、シクロヘプタノール、シクロオクタノールなどの置換基（アルキル基など）を有していてもよい炭素数３〜１２程度の脂環族アルコール；１，１−ジフェニルメタノール、２−フェニル−２−エタノール、１，１−ジフェニルエタノールなどの芳香族アルコール；乳酸、リンゴ酸、酒石酸、マンデル酸、２−ヒドロキシ−４−フェニルブタン酸などのヒドロキシカルボン酸またはその塩などが含まれる。ヒドロキシカルボン酸はα−ヒドロキシカルボン酸である場合が多い。ヒドロキシカルボン酸の塩には、例えば、無機塩基との塩（アンモニウム塩、ナトリウム塩、カリウム塩などのアルカリ金属塩など）、有機塩基との塩（トリメチルアミン、トリエチルアミンなどのアミン類との塩など）が含まれる。
【００１４】
多価アルコールには、例えば、１，２−プロパンジオール、１，２−ブタンジオール、１，３−ブタンジオール、２，３−ブタンジオール、１，２−ペンタンジオール、１，３−ペンタンジオール、２，３−ペンタンジオール、１，２−ヘキサンジオール、１，３−ヘキサンジオール、１，４−ヘキサンジオール、２，３−ヘキサンジオール、２，４−ヘキサンジオール、２，５−ヘキサンジオール、１，２−オクタンジオールなどの炭素数３〜２０程度の脂肪族多価アルコール；１，２−シクロペンタンジオール、１，３−シクロペンタンジオール、１，２−シクロヘキサンジオール、１，３−シクロヘキサンジオール、１，４−シクロヘキサンジオール、１，２−シクロヘプタンジオール、１，３−シクロヘプタンジオール、１，４−シクロヘプタンジオール、１，２−シクロオクタンジオール、１，３−シクロオクタンジオール、１，４−シクロオクタンジオール、１，５−シクロオクタンジオール、ビス（４−ヒドロキシシクロヘキシル）メタン、１，１−ビス（４−ヒドロキシシクロヘキシル）エタン、２，２−ビス（４−ヒドロキシシクロヘキシル）プロパン、メントール、ボルネオールなどの脂環族多価アルコール；単糖類（例えば、トレオース、アラビノース、リボース、キシロース、グルコース、ガラクトース、マンノース、フルクトースなど）、２〜１０の単糖単位を含むオリゴ糖類（例えば、スクロース、マルトース、ラクトースなどの２糖類；ラフィノースなどの３糖類など）、１１以上の単糖単位を含む多糖類（デンプン、可溶性デンプンなど）などの糖類；ペンタエリトリット、エリトリット、アラビット、キシリット、ソルビット、マンニット、イノシットなどの糖アルコール；ソルビットの分子内脱水縮合物（１，４−ソルビタン、３，６−ソルビタン、１，５−ソルビタン、１，４，３，６−ソルビドなど）、マンニットの分子内脱水縮合物（マンニタンなど）などの鎖状糖アルコールの分子内脱水縮合生成物；およびコレステロール、テストステロールなどのステロイド化合物などが含まれる。
【００１５】
これらの二級アルコールは、二重結合などの不飽和結合を有していてもよく、ハロゲン原子、アルコキシ基（例えば、Ｃ_1-6 低級アルコキシ基）、カルボニル基、アシル基（例えば、Ｃ_1-7 低級アシル基）、カルボキシル基、アルコキシカルボニル基（例えば、Ｃ_1-6 低級アルコキシ−カルボニル基）、アミノ基、アルキルアミノ基（例えば、モノ−又はジ−Ｃ_1-4 アルキルアミノ基）や、前記カルボキシル基などの官能基を有するアルコールであってもよい。
【００１６】
ケトンの生成反応において、二級アルコールとしては、二級ヒドロキシル基を有する一価又は多価の脂肪族アルコール（例えば、Ｃ_3-10アルコール又はＣ_3-10ジオールなど）や、脂環族アルコール（例えば、Ｃ_4-10シクロアルカン環を有する脂環族アルコールなど）、特に脂環族アルコールを用いる場合が多い。
【００１７】
本発明の特色は、特定の酸で調整した酸性条件下、前記臭素酸又はその塩とを組み合わせた反応系で、二級アルコールを酸化し、対応するケトンを得る点にある。前記酸としては、特定の無機酸、有機酸が使用される。無機酸には、塩酸、硫酸、硝酸およびリン酸が含まれる。有機酸には、有機カルボン酸（例えば、ギ酸、酢酸、トリクロロ酢酸、トリフルオロ酢酸、プロピオン酸などの飽和カルボン酸、アクリル酸、メタクリル酸などの不飽和カルボン酸、シュウ酸、マロン酸、コハク酸などの飽和ジカルボン酸、マレイン酸などの不飽和ジカルボン酸、グリコール酸、乳酸、リンゴ酸、酒石酸、クエン酸などのなどのオキシカルボン酸など）、スルホン酸（例えば、メタンスルホン酸、エタンスルホン酸、ｐ−トルエンスルホン酸、ベンゼンスルホン酸など）が含まれる。有機酸のうち有機カルボン酸を用いる場合が多い。また、有機酸のうち、水溶性有機酸（例えば、水溶性有機カルボン酸）、特に酢酸などの飽和カルボン酸などを用いる場合が多い。これらの酸成分は、単独で又は二種以上組み合わせて使用でき、前記無機酸と有機酸とを組み合わせて使用してもよい。
【００１８】
前記無機酸又は有機酸で調整される反応系は、酸性であればよく、ｐＨ７未満（例えば、０．１〜６程度）、好ましくはｐＨ５以下（例えば、０．５〜４程度）、さらに好ましくはｐＨ４以下（例えば、０．５〜３程度）である。なお、極度の強酸性条件では、基質や反応生成物が分解するなどの悪影響を及ぼす虞がある。
【００１９】
前記無機酸又は有機酸の使用量は、酸化反応を促進できる範囲で選択でき、例えば、臭素酸又はその塩を臭素酸に換算したとき、臭素酸１モルに対して、１〜１０当量、好ましくは１〜５当量、さらに好ましくは１〜２．５当量程度であり、１〜１．２当量程度である場合が多い。ただし、これらの酸が反応条件下、液体である場合には溶媒として用いることもできる。また、遊離の臭素酸が存在し、反応系が十分に酸性である場合には、他の酸を用いてもよく、用いなくてもよい。
【００２０】
本発明で用いる臭素酸又はその塩は、式 Ｍ（ＢｒＯ₃ ）_n で表される。
（式中、Ｍは水素原子又は金属、ｎは１又は前記金属の価数を示す）
Ｍで表される金属の種類は、臭素酸の活性を損わない限り特に制限されず、例えば、Ｎａ，Ｋ，Ｌｉなどのアルカリ金属（周期表１Ａ族金属）、Ｍｇ，Ｃａ，Ｓｒ，Ｂａなどのアルカリ土類金属（周期表２Ａ族金属）、Ｓｃ，Ｙなどの周期表３Ａ族金属、Ｔｉ，Ｚｒなどの周期表４Ａ族金属、Ｖ、Ｎｂなどの周期表５Ａ族金属、Ｃｒ，Ｍｏ，Ｗなどの周期表６Ａ族金属、Ｍｎ，Ｔｃなどの周期表７Ａ族金属、Ｆｅ，Ｒｕ，Ｃｏ，Ｒｈ，Ｎｉ，Ｐｄ，Ｐｔなどの遷移金属（周期表８族金属）、Ｃｕ，Ａｇ，Ａｕなどの周期表１Ｂ族金属、Ｚｎ，Ｃｄなどの周期表２Ｂ族金属、Ａｌ，Ｇａなどの周期表３Ｂ族金属、Ｓｎ，Ｐｂなどの周期表４Ｂ族金属、Ｓｂ，Ｂｉなどの周期表５Ｂ族金属などが含まれる。好ましい金属Ｍは、水溶性臭素酸塩を形成する場合が多い。
【００２１】
好ましいＭには、水素原子又は１〜３価金属、例えば、アルカリ金属（ナトリウム、カリウムなど）、アルカリ土類金属（マグネシウム、カルシウム、バリウムなど）、アルミニウムなどの周期表３Ｂ族金属、銀などの周期表１Ｂ族金属などが含まれる。経済性および安全性などを考慮すると、前記Ｍはナトリウム、カリウムなどのアルカリ金属である場合が多い。なお、アルカリ土類金属塩、銀塩などの難溶性塩を形成しやすい金属塩を用いると、反応溶媒から分離しやすく、分離精製操作が容易となるなどの利点が生じる場合もある。
ｎは１又は前記金属Ｍの価数であり、１〜３程度である場合が多い。
【００２２】
臭素酸又はその塩の具体例としては、例えば、臭素酸、臭素酸アルカリ金属塩（臭素酸ナトリウムＮａＢｒＯ₃ 、臭素酸カリウムＫＢｒＯ₃ 、臭素酸リチウムなど）、臭素酸アルカリ土類金属塩（臭素酸マグネシウム、臭素酸カルシウムなど）、臭素酸亜鉛、臭素酸アルミニウム、臭素酸銀などが挙げられる。これらの臭素酸又はその塩は単独で又は二種以上組み合わせて使用できる。
二級アルコールの酸化には臭素酸を用いてもよいが、安定で取扱いが容易な臭素酸塩、特に臭素酸アルカリ金属を用いるのが有利である。
なお、前記臭素酸又はその塩は、反応系中で生成すればよく、例えば、臭素酸アルカリ金属塩は、対応するアルカリ金属水酸化物を含む水溶液に臭素を吹き込むことにより生成させてもよい。前記臭素酸又はその塩は、結晶などの固体、水溶液、又は適当な有機溶媒溶液として使用でき、水溶液として使用する場合が多い。
【００２３】
前記酸による酸性条件下、臭素酸又はその塩で二級アルコールを酸化すると、少量の臭素酸又はその塩で効率よく酸化でき、対応するケトンを高い収率で得ることができる。臭素酸又はその塩の使用量は、臭素酸換算で、例えば、基質二級アルコールのうち酸化されるべき二級ヒドロキシル基に対して０．４モル当量以上であって１モル当量未満、好ましくは０．４〜０．８モル当量、さらに好ましくは０．４〜０．７モル当量程度であり、０．４〜０．６モル当量程度である場合が多い。なお、一級ヒドロキシル基と二級ヒドロキシル基とを有する基質アルコールや、複数の二級ヒドロキシル基を有する基質アルコールにおいては、少なくとも酸化されるべき二級アルコール基に対して、前記の量の臭素酸又はその塩を使用すればよい。
なお、反応系において基質アルコールと臭素酸又はその塩の濃度は、反応操作性などを損わない限り特に制限されない。工業的に実施する場合には、基質アルコールの濃度０．０１〜１０モル／Ｌ、好ましくは０．０５〜５モル／Ｌ、さらに好ましくは０．０５〜１モル／Ｌ程度である。ただし、基質アルコールが反応条件下で液体である場合、基質アルコールの一部又は全部を溶媒として用いることも可能である。
【００２４】
このような反応では、前記二級アルコールに対応するケトンとともに臭素が生成するようである。そのため、本発明の方法は、従来の方法と異なり、次のような反応過程を経て進行するものと推測される。

（式中、Ｍは前記金属、ｎは金属の価数、ＨＡは前記有機酸又は無機酸（プロトン酸）、Ａは共役塩基、Ｒ¹およびＲ²は前記に同じ）
このような反応過程からすると、酸化されるべき二級ヒドロキシル基に対して０．４モル当量の臭素酸を用いることにより、酸化反応は、定量的に進行するはずであり、事実、少量の臭素酸又はその塩により酸化反応が高い転化率および選択率で進行する。
【００２５】
二級アルコールの酸化反応は、通常、液相で行なう場合が多く、溶媒の種類は反応に対して不活性であれば特に制限されない。二級アルコールの液相酸化は、臭素酸又はその塩が通常水溶性であるため、溶解性や取り扱い性などの点から、溶媒の少なくとも一部に水を用いるのが適当である。また、基質アルコールが水に対して不溶、微溶又は難溶である場合には、適当な有機溶媒を用いるのが好ましい。このような有機溶媒には、水に対して混和性又は相溶性を有し、反応に不活性な有機溶媒［例えば、アセトニトリル、ホルムミド、ジメチルホルムアミド、ジメチルスルホキシド、ケトン類（アセトンなど）、エーテル類（ジオキサン、テトラヒドロフランなど）、低級カルボン酸（例えば、ギ酸、酢酸など）、三級アルコール（ｔ−ブタノールなど）またはこれらの混合溶媒］、水に対して非混和性であり、反応に不活性な有機溶媒［例えば、脂肪族炭化水素（ペンタン、ヘキサン、オクタンなど）、脂環族炭化水素（シクロヘキサンなど）、芳香族炭化水素（ベンゼン、トルエン、キシレンなど）、ハロゲン化炭化水素（塩化メチレン、クロロホルム、１，２−ジクロロエタンなど）、ケトン類（メチルエチルケトン、メチルイソブチルケトンなど）、エステル類（酢酸メチル、酢酸エチルなど）、エーテル類（ジエチルエーテルなど）又はこれらの混合溶媒など］が含まれる。
【００２６】
溶媒として、水と有機溶媒とを併用する場合、反応系が均一系又は不均一系（水相と有機溶媒相との二相系）のいずれであっても、反応は円滑に進行する。例えば、ｔ−ブチルアルコール／水を溶媒として、水に対して不溶な基質アルコール（例えば、２，２−ビス（４−ヒドロキシシクロヘキシル）プロパンなど）を酸化させると、反応が進行するにつれて、均一系から不均一系に移行するものの、反応は円滑に進行する。不均一系で反応させる場合、基質アルコールの溶解性などを考慮して、相間移動触媒（例えば、四級アンモニウム塩など）や界面活性剤などを併用してもよい。さらには、基質アルコールを溶媒として利用することもできる。
水と有機溶媒とを併用する場合、水と有機溶媒との割合は特に制限されない。臭素酸又はその塩、および基質アルコールを溶解するためには、例えば、体積比で、水／有機溶媒＝１／１００〜１００００／１００、好ましくは１０／１００〜１０００／１００、さらに好ましくは２０／１００〜５００／１００程度である。
【００２７】
酸化反応において、基質アルコールと臭素酸又はその塩の添加順序などは特に制限されず、全量の基質アルコールと全量の臭素酸又はその塩とを含む混合液系で反応させる方法、基質アルコールの溶液と、臭素酸又はその塩を含む溶液とをそれぞれ滴下する方法などであってもよいが、基質アルコールの溶液に臭素酸又は臭素酸塩を添加するのが操作性などの点から有利である。
本発明の酸化反応において、基質アルコールの種類にもよるが、反応系を特に加熱することなく比較的温和な条件であっても、高い転化率および選択率で反応が円滑に進行する場合が多いだけでなく、反応の進行に伴って発熱する。反応温度は、溶媒の沸点以下であれば特に制限されないが、反応系の除熱効率および加熱エネルギー効率を考慮すると、例えば、−１５０℃〜２５０℃、好ましくは−５０℃〜１５０℃、さらに好ましくは−２０℃〜１２０℃程度であり、２０〜１００℃程度である場合が多い。反応は、常圧又は加圧（例えば、１〜１０ａｔｍ程度）下で行なうことができるが、常圧下で反応させると工業的に有利である。
【００２８】
反応終了後、慣用の分離精製手段、例えば、蒸留、濃縮、溶媒抽出、再結晶、クロマトグラフィーなどにより、目的酸化生成物を容易に分離精製できる。なお、酸化反応による生成物が水に対して不溶性又は難溶性である場合、溶媒によっては、反応終了後に、相分離や沈殿物が生成する場合もあるが、本発明の方法では、転化率及び選択率が高いので、殆どの場合、簡単な抽出操作であっても目的生成物を高い純度で得ることができる。しかも、臭素酸又はその類の未反応物やこれらの分解物は、極めて高い水溶性を示すため、水洗などにより未反応物や不純物を簡単に除去できる。そのため、本発明の方法では、反応終了後、簡単な有機溶剤抽出と水洗浄とを組み合わせるだけで副生物を処理でき、目的とする生成物を高い収率及び高い純度で得ることができる。また、酸成分が特定の無機酸又は有機酸であるため、臭化水素酸を用いる従来の方法に比べて、反応装置などの腐食を抑制することもできる。
このように、本発明の方法では、温和な条件で、高い転化率及び選択率で二級アルコールからケトンを生成できるとともに、分離精製を含む後処理工程を極めて簡素化でき、簡単な操作でケトンを高い収率で得ることができる。そのため、工業的及び経済的に極めて有利にケトンを製造できる。
【００２９】
【発明の効果】
本発明の方法では、特定の酸成分の存在下、臭素酸又はその塩で二級アルコールを酸化するため、少量の臭素酸又はその塩で、二級アルコールから対応するケトン類を高い転化率および選択率で製造できる。また、臭素酸又はその塩を用いることに加えて、その使用量が少量であるため、目的化合物の分離精製も容易であり、副生物の処理負荷を大きく低減できるとともに、装置材料の腐食を抑制でき、工業的および経済的に有利にケトンを製造できる。
【００３０】
【実施例】
以下に、実施例に基づいて本発明をより詳細に説明するが、本発明はこれらの実施例により限定されるものではない。
実施例１
２，２−ビス（４−ヒドロキシシクロヘキシル）プロパン２．４０ｇ（１０ミリモル）と酢酸１６ｍｌとの溶液に、撹拌下、臭素酸ナトリウム１．５１ｇ（１０ミリモル）と水１２ｍｌとの溶液を１５分間に亘り滴下した。前記溶液の滴下にともなって臭素が生成し、反応混合液の温度が４９℃まで上昇した。滴下終了後、滴下時間も含めて４時間撹拌した。なお、反応系のｐＨは約４であった。
反応終了後、反応混合液をクロロホルム約５０ｍｌで３回抽出し、有機層を集めて、飽和チオ硫酸ナトリウム水溶液で洗浄した後、硫酸マグネシウムで乾燥し、濾過、濃縮したところ、２，２−ビス（４−オキシシクロヘキシル）プロパンが転化率１００％、収率８０％で得られた。なお、生成物の同定はスペクトルデータと文献値との対比により行ない、収率はＮＭＲスペクトルから算出した。
【００３１】
実施例２
２，２−ビス（４−ヒドロキシシクロヘキシル）プロパン２．４０ｇ（１０ミリモル）とｔ−ブタノール１０ｍｌとの溶液に１．６７Ｎ塩酸６ｍｌ（ＨＣｌとして１０ミリモル）を添加し、この混合液に、撹拌下、臭素酸ナトリウム１．５１ｇ（１０ミリモル）と水１２ｍｌとの溶液を１５分間に亘り滴下した。前記溶液の滴下にともなって臭素が生成し、反応混合液の温度が５２℃まで上昇した。滴下終了後、滴下時間も含めて４時間撹拌した。なお、反応系のｐＨは約４であった。
反応終了後、実施例１と同様にして反応生成物を分離し定量したところ、２，２−ビス（４−オキシシクロヘキシル）プロパンが転化率１００％、収率９７％で得られた。
【００３２】
実施例３
塩酸に代えて、１．６７Ｎ硫酸６ｍｌ（Ｈ₂ＳＯ₄として５ミリモル）を用いる以外、実施例２と同様にして反応させたところ、臭素酸ナトリウム水溶液の滴下にともなって臭素が生成し、反応混合液の温度が５６℃まで上昇した。なお、反応系のｐＨは約１〜３であった。そして、実施例１と同様にして反応生成物を分離し定量したところ、２，２−ビス（４−オキシシクロヘキシル）プロパンが転化率１００％、収率９６％で得られた。
【００３３】
実施例４
２，２−ビス（４−ヒドロキシシクロヘキシル）プロパンのｔ−ブタノール溶液に代えて、１，２−プロパンジオール０．７６ｇ（１０ミリモル）とアセトニトリル（１６ｍｌ）との溶液を用いる以外、実施例２と同様にして反応させた。滴下開始から反応終了時までの反応液のｐＨは約１であった。反応終了後、反応混合物を飽和チオ硫酸ナトリウム水溶液で処理し、ガスクロマトグラフィーにより分析したところ、ヒドロキシアセトンが収率３０％で得られた。
【００３４】
実施例５
２−ヒドロキシ−４−フェニルブタン酸カリウム塩（４ミリモル）および他のカルボン酸カリウム塩の混合物（合計２４．５ミリモル）を含む水溶液３８．１ｇと、アセトニトリル（１０ｍｌ）、３５％塩酸３．２３ｇ（ＨＣｌとして３１ミリモル）との混合液に、室温で、撹拌しながら、臭素酸ナトリウム０．３０ｇ（２ミリモル）および水（１２ｍｌ）の溶液を１５分間に亘り滴下した。滴下終了後、滴下時間を含めて４時間撹拌した。なお、反応系のｐＨは約２〜３であった。
反応終了後、反応混合物を実施例１と同様にして処理し、得られた濃縮物を液体クロマトグラフィーにより分析したところ、２−オキソ−４−フェニルブタン酸が収率４９％で得られた。
【００３５】
比較例
臭素酸ナトリウムに代えて、塩素酸ナトリウム１．０６ｇ（１０ミリモル）を用いる以外、実施例２と同様にして反応させたところ、反応系のｐＨが約１であったものの、反応が全く進行せず、原料の２，２−ビス（４−ヒドロキシシクロヘキシル）プロパンの全量が回収された。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a corresponding ketone by oxidizing a secondary alcohol, and particularly to an improved method for converting a commercially available secondary alcohol to ketones in one step.
[0002]
[Prior art]
Various reactions such as oxidation with chromic acid, oxidation with manganese dioxide, oxidation with dimethyl sulfoxide represented by swan oxidation, oxidation with hypohalite or halogenate can be used to convert alcohol to ketone by oxidation. In addition, oxidation by carbonyl compounds represented by opener oxidation, oxidation by selenium compounds, oxidation by transition metal catalysts such as ruthenium, etc. are known (Chemical Society of Japan, "Experimental Chemistry Course Organic Synthesis III-Aldehyde, Ketone, Quinone"). -", 4th edition, Maruzen Co., Ltd., 1991, 21, 196-240).
[0003]
Each of these reactions has characteristics depending on the type of oxidizing agent. However, in the oxidation with chromic acid, manganese dioxide, and selenium compound, it is necessary to treat the remaining harmful metal compound after the reaction is completed. Furthermore, the oxidation with dimethyl sulfoxide and the opener oxidation require a co-oxidant, and the method using a transition metal catalyst requires the use of an expensive catalyst.
[0004]
From this point of view, it is advantageous to oxidize using hypohalite or halogenate as an oxidizing agent, and reaction using hypohalous acid, halogenous acid, halogen acid or salts thereof as oxidizing agent. Has been proposed. In particular, hypohalites, especially sodium hypochlorite (antiformyl) and calcium hypochlorite (salasi powder) are widely used as oxidizing agents because they are inexpensive and easily available industrially. ing. For example, JP-A-4-59742 discloses that 2,2-bis (4-hydroxycyclohexyl) propane is oxidized with hypochlorous acid or a salt thereof, and 2,2-bis (4- It is disclosed to obtain oxycyclohexyl) propane.
However, in a reaction using hypohalous acid or a salt thereof as an oxidizing agent, at least an equimolar amount of hypohalous acid or a salt thereof in terms of hypohalous acid is required for the hydroxyl group of the alcohol to be oxidized. is there. That is, when such an oxidation reaction is carried out industrially, it is necessary to treat, detoxify and discharge a compound containing at least 1 gram atom of halogen with respect to 1 mol of the product.
[0005]
In order to reduce the processing load of the halogen-containing compound, it may be advantageous to use a halogen acid, a halogen acid or a salt thereof having a large oxygen / halogen ratio as an oxidizing agent. When halogenous acid or its salt is used as an oxidizing agent, there are many examples of using sodium bromite useful for selective oxidation of secondary alcohol (edited by the Chemical Society of Japan, “Experimental Chemistry Course Organic Synthesis III-Aldehyde / Ketone ・"Quinone", 4th edition, Maruzen Co., Ltd., 1991, 21, 219, and Journal of Organic Synthetic Chemistry, 42, 751 (1984)). An example of converting various secondary alcohols to ketones using sodium bromite has also been reported (Kageyama, Synthesis, page 815, (1984)). However, in order to obtain a ketone with a high yield, an excess amount of sodium bromite of 3 molar equivalents relative to the substrate alcohol is used.
[0006]
On the other hand, when a halogen acid or a salt thereof is used as an oxidizing agent, the amount used is small compared to hypohalous acid, halous acid or a salt thereof. For example, JP-A-1-305053 discloses a method for producing an α-ketoester by oxidizing an α-oxyester with a bromate in the presence of a ruthenium catalyst, an onium salt and an orthophosphate. . However, this oxidation system not only requires an expensive ruthenium catalyst, but also uses 2 mol times bromate with respect to the substrate. In JP-A-2-157247, 1-acyloxy-3-chloro-2-propanol is oxidized using bromate and sulfamic acid to produce 1-acyloxy-3-chloro-2-propanone. A method is disclosed. This document also states that it is preferable to use equimolar or more bromate with respect to the substrate.
[0007]
Furthermore, using sodium bromate-hydrobromic acid system, synthesis of esters from alcohols and ethers, synthesis of lactones from thiols, and synthesis of ketones from secondary alcohols have also been reported (Bulletin of the Chemical Society of Japan). 59, 77 (1986)). This document describes that in the conversion of secondary alcohol to ketone, the oxidation reaction proceeds almost quantitatively when 0.5 molar equivalent of sodium bromate is used with respect to the hydroxyl group of the secondary alcohol. Has been. Furthermore, according to the theory described in this document, the theoretical minimum amount of sodium bromate required is 0.33 molar equivalents relative to the hydroxyl group of the alcohol being oxidized. However, a catalytic amount of hydrobromic acid is essential for the reaction to proceed through the route described in this document. Furthermore, this reaction is not only a reaction in which water is produced, but water is used as a part of the solvent. In the presence of water, hydrobromic acid is highly corrosive to apparatus materials, so the use of hydrobromic acid is industrially disadvantageous. Hydrobromic acid is expensive and highly toxic.
[0008]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a method for producing a corresponding ketone from a secondary alcohol with a high conversion and selectivity using a small amount of bromic acid or a salt thereof.
Another object of the present invention is to provide a method capable of greatly reducing the processing load of by-products and suppressing corrosion of apparatus materials, and producing a ketone industrially advantageously.
[0009]
[Means for Solving the Problems]
As a result of intensive studies to achieve the above object, the present inventors oxidized brominic acid or a salt thereof under acidic conditions adjusted with a specific inorganic acid or organic acid to produce bromine, As a result of finding out that it can be efficiently and quantitatively oxidized with a small amount of bromic acid or a salt thereof, the present invention was completed as a result of further investigation.
[0010]
  That is, in the method of the present invention, in the presence of at least one inorganic acid or organic acid selected from hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid,Without using a metal compound, bromine or iodine as a catalyst,0.4 mol equivalent or more and less than 1 mol equivalent of bromic acid or a salt thereof in terms of bromic acid with respect to the hydroxyl group of the secondary alcoholAs an oxidantUsed to produce ketones by oxidizing secondary alcohols.
  In this reaction, the amount of bromic acid or a salt thereof used may be about 0.4 to 0.8 molar equivalent relative to the hydroxyl group of the secondary alcohol, and the secondary alcohol is an alicyclic alcohol. Also good. The organic acid includes an organic carboxylic acid.
  Furthermore, the method of the present invention includes acidic conditions adjusted with at least one inorganic acid or water-soluble organic carboxylic acid selected from hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid,Without using a metal compound, bromine or iodine as a catalyst,0.4 to 0.7 molar equivalent of alkali metal bromate with respect to the hydroxyl group of the secondary alcoholAs an oxidantAlso included is a method of oxidizing secondary alcohols to produce the corresponding ketone and bromine..
  As used herein, “secondary alcohol” means an alcohol having at least one secondary hydroxyl group. The secondary alcohol may be simply referred to as “alcohol”.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
In the method of the present invention, the corresponding ketone (2) is produced from the secondary alcohol (1) as represented by the following reaction formula.
[0012]
[Chemical 1]

(Wherein R¹And R²Are the same or different and each represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an aralkyl group, and R¹And R²May combine with each other to form a non-aromatic ring)
In the above formula, R¹And R²In the alkyl group represented by the formula, linear or branched C_1-20An alkyl group (preferably C_1-10Alkyl group), and alkenyl groups include, for example, vinyl, 1-propenyl, 2-propenyl, isopropenyl, butenyl, pentenyl groups, and the like._2-10Alkenyl groups are included, and alkynyl groups include, for example, C such as ethynyl and propynyl groups._2-10Alkynyl groups are included.
R¹And R²As the cycloalkyl group represented by, for example, C such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like._3-20A cycloalkyl group (preferably C_4-10Cycloalkyl group), and aralkyl groups include, for example, C such as benzyl and phenethyl groups._6-12Aryl-C_1-4Alkyl groups and the like are included.
[0013]
Secondary alcohols include monohydric alcohols and polyhydric alcohols having secondary hydroxyl groups. Among the secondary alcohols, the monohydric alcohol includes, for example, carbon numbers such as 2-propanol, 2-butanol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 2-heptanol, and 2-octanol. About 1 to 20 aliphatic alcohols; cyclopentanol, cyclohexanol, 2-methylcyclohexanol, 3-methylcyclohexanol, 4-methylcyclohexanol, 4-t-butylcyclohexanol, cycloheptanol, cyclooctanol, etc. C3-C12 alicyclic alcohol which may have a substituent (such as an alkyl group); Fragrance such as 1,1-diphenylmethanol, 2-phenyl-2-ethanol, 1,1-diphenylethanol Group alcohol; lactic acid, malic acid, tartaric acid, mandelic acid Such as hydroxycarboxylic acids or salts thereof, such as 2-hydroxy-4-phenyl-butanoic acid are included. The hydroxycarboxylic acid is often an α-hydroxycarboxylic acid. Examples of hydroxycarboxylic acid salts include salts with inorganic bases (such as alkali metal salts such as ammonium salts, sodium salts, and potassium salts) and salts with organic bases (such as salts with amines such as trimethylamine and triethylamine). Is included.
[0014]
Examples of the polyhydric alcohol include 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,3-pentanediol, 2,3-pentanediol, 1,2-hexanediol, 1,3-hexanediol, 1,4-hexanediol, 2,3-hexanediol, 2,4-hexanediol, 2,5-hexanediol, 1 Aliphatic polyhydric alcohols having about 3 to 20 carbon atoms such as 1,2-octanediol; 1,2-cyclopentanediol, 1,3-cyclopentanediol, 1,2-cyclohexanediol, 1,3-cyclohexanediol, 1,4-cyclohexanediol, 1,2-cycloheptanediol, 1,3-cycloheptanediol, 1,4-si Loheptanediol, 1,2-cyclooctanediol, 1,3-cyclooctanediol, 1,4-cyclooctanediol, 1,5-cyclooctanediol, bis (4-hydroxycyclohexyl) methane, 1,1-bis (4-hydroxycyclohexyl) ethane, alicyclic polyhydric alcohols such as 2,2-bis (4-hydroxycyclohexyl) propane, menthol and borneol; monosaccharides (eg, threose, arabinose, ribose, xylose, glucose, galactose, Mannose, fructose, etc.) Oligosaccharides containing 2 to 10 monosaccharide units (eg, disaccharides such as sucrose, maltose, lactose; trisaccharides such as raffinose), polysaccharides containing 11 or more monosaccharide units (starch) , Soluble starch, etc.) Kinds: Sugar alcohols such as pentaerythritol, erythritol, arabit, xylit, sorbit, mannitol, inosit; intramolecular dehydration condensates of sorbit (1,4-sorbitan, 3,6-sorbitan, 1,5-sorbitan, 1 , 4,3,6-sorbide, etc.), intramolecular dehydration condensation products of chain sugar alcohols such as intramolecular dehydration condensates of mannit (such as mannitan); and steroid compounds such as cholesterol and testosterol. .
[0015]
These secondary alcohols may have an unsaturated bond such as a double bond, a halogen atom, an alkoxy group (for example, C_1-6Lower alkoxy group), carbonyl group, acyl group (for example, C_1-7Lower acyl group), carboxyl group, alkoxycarbonyl group (for example, C_1-6Lower alkoxy-carbonyl group), amino group, alkylamino group (eg mono- or di-C)_1-4Alkylamino groups) and alcohols having functional groups such as carboxyl groups may be used.
[0016]
In the ketone formation reaction, the secondary alcohol may be a monohydric or polyhydric aliphatic alcohol having a secondary hydroxyl group (for example, C_3-10Alcohol or C_3-10Diols) and alicyclic alcohols (eg C_4-10In many cases, an alicyclic alcohol having a cycloalkane ring or the like, particularly an alicyclic alcohol is used.
[0017]
The feature of the present invention is that a secondary alcohol is oxidized to obtain a corresponding ketone under a reaction system in which the bromic acid or its salt is combined under acidic conditions adjusted with a specific acid. As the acid, a specific inorganic acid or organic acid is used. Inorganic acids include hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid. Organic acids include organic carboxylic acids (for example, saturated carboxylic acids such as formic acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, propionic acid, unsaturated carboxylic acids such as acrylic acid and methacrylic acid, oxalic acid, malonic acid, and succinic acid. Saturated dicarboxylic acids such as, unsaturated dicarboxylic acids such as maleic acid, oxycarboxylic acids such as glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, etc.), sulfonic acids (eg, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, etc.). Of the organic acids, organic carboxylic acids are often used. Of the organic acids, water-soluble organic acids (for example, water-soluble organic carboxylic acids), particularly saturated carboxylic acids such as acetic acid, are often used. These acid components can be used alone or in combination of two or more thereof, and the inorganic acid and the organic acid may be used in combination.
[0018]
The reaction system adjusted with the inorganic acid or organic acid only needs to be acidic, and is less than pH 7 (for example, about 0.1 to 6), preferably 5 or less (for example, about 0.5 to 4), more preferably. Is pH 4 or less (for example, about 0.5 to 3). Under extremely strong acidic conditions, there is a risk of adverse effects such as decomposition of substrates and reaction products.
[0019]
The amount of the inorganic acid or organic acid used can be selected within a range that can promote the oxidation reaction. For example, when bromic acid or a salt thereof is converted to bromic acid, 1 to 10 equivalents, preferably 1 mol of bromic acid Is about 1 to 5 equivalents, more preferably about 1 to 2.5 equivalents, often about 1 to 1.2 equivalents. However, when these acids are liquid under the reaction conditions, they can also be used as a solvent. In addition, when free bromic acid is present and the reaction system is sufficiently acidic, other acids may or may not be used.
[0020]
The bromic acid or salt thereof used in the present invention has the formula M (BrO_Three)_nIt is represented by
(In the formula, M represents a hydrogen atom or a metal, n represents 1 or the valence of the metal)
The type of metal represented by M is not particularly limited as long as it does not impair the activity of bromic acid. For example, alkali metals such as Na, K, Li (Group 1A metal of the periodic table), Mg, Ca, Sr, Ba Alkaline earth metals (Group 2A metals) such as Sc, Y, Group 3A metals such as Sc and Y, Group 4A metals such as Ti and Zr, Group 5A metals such as V and Nb, Cr, Mo , W, periodic table group 6A metals, Mn, Tc, etc. periodic table group 7A metals, Fe, Ru, Co, Rh, Ni, Pd, Pt transition metals (periodic group 8 metals), Cu, Ag, Periodic table 1B metal such as Au, periodic table 2B metal such as Zn and Cd, periodic table 3B metal such as Al and Ga, periodic table 4B metal such as Sn and Pb, periodic table 5B such as Sb and Bi Group metals and the like are included. Preferred metals M often form water-soluble bromates.
[0021]
Preferred M is a hydrogen atom or a 1-3 valent metal such as alkali metals (sodium, potassium, etc.), alkaline earth metals (magnesium, calcium, barium, etc.), periodic table group 3B metals such as aluminum, silver, etc. Periodic table 1B group metals and the like are included. In consideration of economy and safety, M is often an alkali metal such as sodium or potassium. When a metal salt that easily forms a hardly soluble salt such as an alkaline earth metal salt or a silver salt is used, there are cases where advantages such as easy separation from the reaction solvent and easy separation and purification operations may occur.
n is 1 or the valence of the metal M, and is often about 1 to 3.
[0022]
Specific examples of bromic acid or salts thereof include, for example, bromic acid, alkali metal bromate (sodium bromate NaBrO_Three, Potassium bromate KBrO_Three, Lithium bromate, etc.), alkaline earth metal bromates (magnesium bromate, calcium bromate, etc.), zinc bromate, aluminum bromate, silver bromate and the like. These bromic acids or salts thereof can be used alone or in combination of two or more.
Bromic acid may be used for the oxidation of the secondary alcohol, but it is advantageous to use a bromate which is stable and easy to handle, especially an alkali metal bromate.
In addition, what is necessary is just to produce | generate the said bromic acid or its salt in a reaction system, for example, you may produce | generate an alkali metal bromate by blowing bromine into the aqueous solution containing a corresponding alkali metal hydroxide. The bromic acid or a salt thereof can be used as a solid such as a crystal, an aqueous solution, or an appropriate organic solvent solution, and is often used as an aqueous solution.
[0023]
When the secondary alcohol is oxidized with bromic acid or a salt thereof under acidic conditions with the acid, it can be efficiently oxidized with a small amount of bromic acid or a salt thereof, and the corresponding ketone can be obtained in a high yield. The amount of bromic acid or its salt used is, in terms of bromic acid, for example, 0.4 molar equivalent or more and less than 1 molar equivalent relative to the secondary hydroxyl group to be oxidized in the substrate secondary alcohol, preferably It is about 0.4 to 0.8 molar equivalent, more preferably about 0.4 to 0.7 molar equivalent, and often about 0.4 to 0.6 molar equivalent. In the case of a substrate alcohol having a primary hydroxyl group and a secondary hydroxyl group or a substrate alcohol having a plurality of secondary hydroxyl groups, at least the secondary alcohol group to be oxidized, the above amount of bromic acid or The salt may be used.
The concentration of substrate alcohol and bromic acid or a salt thereof in the reaction system is not particularly limited as long as the reaction operability is not impaired. When it implements industrially, the density | concentration of substrate alcohol is 0.01-10 mol / L, Preferably it is 0.05-5 mol / L, More preferably, it is about 0.05-1 mol / L. However, when the substrate alcohol is liquid under the reaction conditions, part or all of the substrate alcohol can be used as a solvent.
[0024]
In such a reaction, bromine appears to be produced along with the ketone corresponding to the secondary alcohol. Therefore, unlike the conventional method, the method of the present invention is presumed to proceed through the following reaction process.

Wherein M is the metal, n is the valence of the metal, HA is the organic acid or inorganic acid (protonic acid), A is a conjugate base, R¹And R²Is the same as above)
From such a reaction process, the oxidation reaction should proceed quantitatively by using 0.4 molar equivalents of bromic acid relative to the secondary hydroxyl group to be oxidized, and in fact, a small amount of bromine The oxidation reaction proceeds with high conversion and selectivity by the acid or its salt.
[0025]
The secondary alcohol oxidation reaction is usually carried out in a liquid phase, and the type of solvent is not particularly limited as long as it is inert to the reaction. In the liquid phase oxidation of the secondary alcohol, since bromic acid or a salt thereof is usually water-soluble, it is appropriate to use water as at least a part of the solvent from the viewpoint of solubility and handleability. When the substrate alcohol is insoluble, slightly soluble or hardly soluble in water, it is preferable to use an appropriate organic solvent. Such organic solvents are miscible or compatible with water and are inert to the reaction [for example, acetonitrile, formamide, dimethylformamide, dimethyl sulfoxide, ketones (acetone, etc.), ethers. (Dioxane, tetrahydrofuran, etc.), lower carboxylic acids (for example, formic acid, acetic acid, etc.), tertiary alcohols (t-butanol, etc., or mixed solvents thereof), immiscible with water and inert to the reaction Organic solvents [for example, aliphatic hydrocarbons (pentane, hexane, octane, etc.), alicyclic hydrocarbons (cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), halogenated hydrocarbons (methylene chloride, chloroform) , 1,2-dichloroethane), ketones (methyl ethyl ketone, methyl isobutyl) Ton, etc.), esters (methyl acetate, ethyl acetate), include ethers (such as diethyl ether), or and mixtures of these solvents.
[0026]
When water and an organic solvent are used in combination as a solvent, the reaction proceeds smoothly regardless of whether the reaction system is a homogeneous system or a heterogeneous system (a two-phase system of an aqueous phase and an organic solvent phase). For example, when t-butyl alcohol / water is used as a solvent to oxidize water-insoluble substrate alcohol (for example, 2,2-bis (4-hydroxycyclohexyl) propane), a homogeneous system is obtained as the reaction proceeds. However, the reaction proceeds smoothly. When the reaction is performed in a heterogeneous system, a phase transfer catalyst (for example, a quaternary ammonium salt) or a surfactant may be used in combination in consideration of the solubility of the substrate alcohol. Furthermore, substrate alcohol can also be used as a solvent.
When water and an organic solvent are used in combination, the ratio of water and the organic solvent is not particularly limited. In order to dissolve bromic acid or a salt thereof and substrate alcohol, for example, by volume ratio, water / organic solvent = 1/100 to 10000/100, preferably 10/100 to 1000/100, more preferably 20 / It is about 100 to 500/100.
[0027]
In the oxidation reaction, the order of addition of substrate alcohol and bromic acid or a salt thereof is not particularly limited, and a method of reacting in a mixed solution system containing a total amount of substrate alcohol and a total amount of bromic acid or a salt thereof, a solution of substrate alcohol, The solution containing bromic acid or a salt thereof may be added dropwise, but it is advantageous from the viewpoint of operability to add bromic acid or bromate to the substrate alcohol solution.
In the oxidation reaction of the present invention, although depending on the type of substrate alcohol, the reaction often proceeds smoothly at a high conversion and selectivity even under relatively mild conditions without particularly heating the reaction system. Not only does it generate heat as the reaction progresses. The reaction temperature is not particularly limited as long as it is not higher than the boiling point of the solvent, but considering the heat removal efficiency and the heating energy efficiency of the reaction system, for example, -150 ° C to 250 ° C, preferably -50 ° C to 150 ° C, more preferably It is about -20 degreeC-120 degreeC, and is about 20-100 degreeC in many cases. The reaction can be carried out under normal pressure or increased pressure (for example, about 1 to 10 atm), but it is industrially advantageous to carry out the reaction under normal pressure.
[0028]
After completion of the reaction, the target oxidation product can be easily separated and purified by conventional separation and purification means such as distillation, concentration, solvent extraction, recrystallization, chromatography and the like. In addition, when the product of the oxidation reaction is insoluble or hardly soluble in water, depending on the solvent, phase separation or precipitate may be generated after the reaction is completed, but in the method of the present invention, the conversion rate and Since the selectivity is high, in most cases the target product can be obtained with high purity even with a simple extraction operation. Moreover, unreacted products such as bromic acid or the like and their decomposition products exhibit extremely high water solubility, so that unreacted materials and impurities can be easily removed by washing with water. Therefore, in the method of the present invention, after the reaction is completed, the by-product can be treated only by combining simple organic solvent extraction and water washing, and the desired product can be obtained with high yield and high purity. Further, since the acid component is a specific inorganic acid or organic acid, corrosion of the reaction apparatus or the like can be suppressed as compared with the conventional method using hydrobromic acid.
As described above, in the method of the present invention, ketones can be produced from secondary alcohols under mild conditions with high conversion and selectivity, and the post-treatment process including separation and purification can be greatly simplified. Can be obtained in high yield. Therefore, a ketone can be produced very advantageously industrially and economically.
[0029]
【The invention's effect】
In the method of the present invention, the secondary alcohol is oxidized with bromic acid or a salt thereof in the presence of a specific acid component. Therefore, with a small amount of bromic acid or a salt thereof, the corresponding ketones are converted from the secondary alcohol with a high conversion rate. Can be manufactured with selectivity. In addition to the use of bromic acid or its salts, the amount used is small, so the separation and purification of the target compound is easy, the processing load of by-products can be greatly reduced, and the corrosion of equipment materials is suppressed. The ketone can be produced industrially and economically advantageously.
[0030]
【Example】
Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.
Example 1
To a solution of 2.40 g (10 mmol) of 2,2-bis (4-hydroxycyclohexyl) propane and 16 ml of acetic acid, with stirring, a solution of 1.51 g (10 mmol) of sodium bromate and 12 ml of water was added over 15 minutes. It was dripped over. Bromine was generated as the solution was added dropwise, and the temperature of the reaction mixture rose to 49 ° C. After completion of the dropping, the mixture was stirred for 4 hours including the dropping time. The pH of the reaction system was about 4.
After completion of the reaction, the reaction mixture was extracted three times with about 50 ml of chloroform, and the organic layer was collected, washed with a saturated aqueous sodium thiosulfate solution, dried over magnesium sulfate, filtered and concentrated. (4-Oxycyclohexyl) propane was obtained with a conversion rate of 100% and a yield of 80%. The product was identified by comparing spectral data with literature values, and the yield was calculated from the NMR spectrum.
[0031]
Example 2
To a solution of 2.40 g (10 mmol) of 2,2-bis (4-hydroxycyclohexyl) propane and 10 ml of t-butanol was added 6 ml of 1.67N hydrochloric acid (10 mmol as HCl), and this mixture was stirred. A solution of sodium bromate 1.51 g (10 mmol) and water 12 ml was added dropwise over 15 minutes. Bromine was generated as the solution was added dropwise, and the temperature of the reaction mixture rose to 52 ° C. After completion of the dropping, the mixture was stirred for 4 hours including the dropping time. The pH of the reaction system was about 4.
After completion of the reaction, the reaction product was separated and quantified in the same manner as in Example 1. As a result, 2,2-bis (4-oxycyclohexyl) propane was obtained with a conversion rate of 100% and a yield of 97%.
[0032]
Example 3
Instead of hydrochloric acid, 6 ml of 1.67N sulfuric acid (H₂SO_FourThe reaction was conducted in the same manner as in Example 2 except that 5 mmol) was used. As a result, bromine was produced as the aqueous sodium bromate solution was dropped, and the temperature of the reaction mixture rose to 56 ° C. The pH of the reaction system was about 1 to 3. When the reaction product was separated and quantified in the same manner as in Example 1, 2,2-bis (4-oxycyclohexyl) propane was obtained with a conversion rate of 100% and a yield of 96%.
[0033]
Example 4
Example 2 except that a solution of 0.76 g (10 mmol) of 1,2-propanediol and acetonitrile (16 ml) was used instead of the t-butanol solution of 2,2-bis (4-hydroxycyclohexyl) propane. The reaction was conducted in the same manner. The pH of the reaction solution from the start of dropping until the end of the reaction was about 1. After completion of the reaction, the reaction mixture was treated with a saturated aqueous sodium thiosulfate solution and analyzed by gas chromatography. As a result, hydroxyacetone was obtained in a yield of 30%.
[0034]
Example 5
38.1 g of an aqueous solution containing a mixture of potassium 2-hydroxy-4-phenylbutanoate (4 mmol) and other carboxylic acid potassium salts (24.5 mmol in total), acetonitrile (10 ml), 3.23 g of 35% hydrochloric acid A solution of 0.30 g (2 mmol) sodium bromate and water (12 ml) was added dropwise to the mixture with (31 mmol as HCl) at room temperature over 15 minutes with stirring. After completion of the dropping, the mixture was stirred for 4 hours including the dropping time. The pH of the reaction system was about 2-3.
After completion of the reaction, the reaction mixture was treated in the same manner as in Example 1. The obtained concentrate was analyzed by liquid chromatography, whereby 2-oxo-4-phenylbutanoic acid was obtained in a yield of 49%.
[0035]
Comparative example
When the reaction was carried out in the same manner as in Example 2 except that 1.06 g (10 mmol) of sodium chlorate was used instead of sodium bromate, the reaction proceeded at all although the pH of the reaction system was about 1. First, the entire amount of raw material 2,2-bis (4-hydroxycyclohexyl) propane was recovered.

Claims (5)

In the presence of at least one inorganic acid or organic acid selected from hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, conversion to bromic acid with respect to the hydroxyl group of the secondary alcohol without using a metal compound, bromine or iodine as a catalyst And a method for producing a ketone in which a secondary alcohol is oxidized using 0.4 mole equivalent or more and less than 1 mole equivalent of bromic acid or a salt thereof as an oxidizing agent .   The method for producing a ketone according to claim 1, wherein the amount of bromic acid or a salt thereof used is 0.4 to 0.8 molar equivalent relative to the hydroxyl group of the secondary alcohol.   The method for producing a ketone according to claim 1, wherein the secondary alcohol is an alicyclic alcohol.   The method for producing a ketone according to claim 1, wherein the organic acid is an organic carboxylic acid. Under acidic conditions adjusted with at least one inorganic acid or water-soluble organic carboxylic acid selected from hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, the hydroxyl group of the secondary alcohol is used without using a metal compound, bromine or iodine as a catalyst. On the other hand, a method of oxidizing a secondary alcohol using 0.4 to 0.7 molar equivalents of an alkali metal bromate as an oxidizing agent to produce a corresponding ketone and bromine .