JP4034889B2 - Process for producing trifluorophenols - Google Patents
Process for producing trifluorophenols Download PDFInfo
- Publication number
- JP4034889B2 JP4034889B2 JP33095498A JP33095498A JP4034889B2 JP 4034889 B2 JP4034889 B2 JP 4034889B2 JP 33095498 A JP33095498 A JP 33095498A JP 33095498 A JP33095498 A JP 33095498A JP 4034889 B2 JP4034889 B2 JP 4034889B2
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- JP
- Japan
- Prior art keywords
- trifluorophenol
- reaction
- trifluorophenols
- producing
- trifluorobenzene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【0001】
【発明の属する技術分野】
本発明は、医薬、農薬、液晶等の重要な中間体となりうるトリフルオロフェノール類を効率よく製造する方法に関するものである。
【0002】
【従来の技術】
従来、フルオロフェノール類の製造方法として、1)フルオロアニリンのジアゾ化後加水分解する方法〔J.Am.Chem.Soc.,61,165(1939) 〕、2)アミノアニソールからシーマン反応によりフルオロアニソールを得た後、メトキシ基を加水分解する方法〔日化 79,1121(1979)〕、3)ポリフルオロベンゼン類をN,N −ジメチルホルムアミド等の非プロトン性極性溶媒中でナトリウムメトキシドと反応させてフッ素が一個減少したフルオロアニソール類を得、次いで加水分解する方法〔特開平9−136853号〕、4)クロロフルオロベンゼンまたはブロモフルオロベンゼンを塩基の存在下で加水分解する方法〔▲1▼J.Fluorine Chem.,50,377,(1990)、▲2▼J.Org.Chem.,26,4641,(1961)〕等が知られている。
しかしながら、上記の方法はいずれも問題点を有している。即ち、1)の方法は収率が低く(特にフッ素の数が増えるにつれてこの傾向がある)、廃物を多量に生じるなど工業的に実用化しうる方法とは言いがたい。2)の方法は工程的に長く、また、反応熱による制御が難しいなどの問題点がある上、特にフッ素を3個入れるのは極めて困難である。3)の方法は収率がよく有用であるが、トリフルオロフェノール類の場合原料となるテトラフルオロベンゼン類の入手が困難である等の問題点を有する。4)の方法はフッ素の数が1〜2個の場合(特に1個のとき)収率が良好であるが、フッ素が3個の場合極端に低下する。
【0003】
【発明が解決しようとする課題】
本発明の課題は、中間体化合物として有用なトリフルオロフェノール類を効率よく製造できる方法を提供することである。
【0004】
かくして本発明者らは、上記5)の方法について、更に鋭意検討を重ねた結果、有用な製造方法を見出した。
【0005】
【課題を解決するための手段】
本発明は、下記一般式(I)で表されるモノブロモトリフルオロベンゼン類を、銅化合物触媒の存在下、水と非プロトン性極性溶媒との混合溶媒中で加熱し加水分解反応を行うことにより、下記一般式(II)で表されるトリフルオロフェノール類を製造する方法を提供するものである。
【0006】
【化3】
【0007】
【化4】
【0008】
即ち、本発明の要旨はモノブロモトリフルオロベンゼン類を加水分解し、トリフルオロフェノール類を製造する方法に存する。
前述の通り、ブロモベンゼン類を銅または銅化合物触媒と塩基化合物の存在下、加水分解反応を行いフェノール類を合成する方法が知られているが、本発明者らの経験ではトリフルオロ誘導体の場合、この反応における既知の条件下では収率が極端に低下した。本発明者らは、当該反応において塩基化合物の使用を止め、スルホランのような非プロトン性極性溶媒を添加することにより収率が顕著に向上することを見出し、本発明に到達したのである。
【0009】
【発明の実施の形態】
以下、本発明を詳細に説明する。
本発明の具体的な実施に際しては、オートクレーブ等に、一般式(I)で表されるモノブロモトリフルオロベンゼン類と銅化合物、水、非プロトン性極性溶媒を仕込み、攪拌下に所定温度で所定時間反応させる。反応終了後、室温まで冷却し、反応物を取り出して希塩酸と抽出用有機溶媒(例えばジクロロメタン)を加え振盪する。この有機相を分取し、次に蒸留により目的とするトリフルオロフェノール類を得る。
【0010】
触媒の銅化合物としては特に限定されないが、酸化第一銅および酸化第二銅が適当である。臭化銅、塩化銅、硫酸銅の場合は触媒効果が小さく、また、銅粉も効果が小さい傾向がある。酸化銅はモノブロモトリフルオロベンゼン類に対してモル比で 0.1〜1.0 好ましくは0.3 〜0.6 の割合で用いる。 0.1以下では添加効果が認められず、また、 1.0以上ではもはや反応速度の増加が認められない。
【0011】
非プロトン性極性溶媒としてはスルホラン、ジメチルスルホキシドや1,3 −ジメチル−2−イミダゾリジノンが使用できるが、副反応の励起がないことからスルホランが特に好ましい。
非プロトン性極性溶媒は水との共溶媒として使用するが、その割合は重量比で0.1〜0.5 好ましくは 0.2〜0.4 が適当である。 0.1以下では添加効果が認められず、また、0.5以上ではもはや反応速度の増加が認められなくなる。
【0012】
本発明の反応温度は、 210〜270 ℃が好ましい。
また、反応時間は3〜10時間が適当である。
【0013】
本発明の一般式(I)に示すモノブロモトリフルオロベンゼン類は六種類の異性体が存在するが、比較的容易に入手できるのは1−ブロモ−3,4,5 −トリフルオロベンゼンと1−ブロモ−2,3,4 −トリフルオロベンゼンである。1−ブロモ−3,4,5 −トリフルオロベンゼンからは3,4,5 −トリフルオロフェノールが、1−ブロモ−2,3,4 −トリフルオロベンゼンからは2,3,4 −トリフルオロフェノールがそれぞれ得られる。
【0014】
【実施例】
以下、実施例により本発明を更に具体的に説明するが、本発明はこれらに限定されるものではない。
実施例1(3,4,5 −トリフルオロフェノールの製造)
500ml ステンレス製オートクレーブに1−ブロモ−3,4,5 −トリフルオロベンゼン52.8g(0.250mol) 、酸化第一銅10g、水135ml 、スルホラン40mlを仕込んだ。攪拌下、 210℃で5時間反応させた。反応終了後、常温まで冷却したのちオートクレーブを開け反応物を1リットルのビーカーに移した。オートクレーブ内はジクロロメタンで洗い、洗浄液を上記ビーカーに加えた。次に、1リットルの分液ロートに移し、ジクロロメタン 150mlを加え、振盪後静置し、有機相を分取した。次いで、この有機相を蒸留し、3,4,5 −トリフルオロフェノール22.6gを得、1−ブロモ−3,4,5 −トリフルオロベンゼンを13.1g回収した。1−ブロモ−3,4,5 −トリフルオロベンゼン基準の選択率は81%であった。
【0015】
実施例2(2,3,4 −トリフルオロフェノールの製造)
1−ブロモ−3,4,5 −トリフルオロベンゼンの代わりに1−ブロモ−2,3,4 −トリフルオロベンゼンを使用した以外は実施例1と同様に行った。3,4,5 −トリフルオロフェノールが20.7g得られ、1−ブロモ−2,3,4 −トリフルオロベンゼンを13.1g回収した。1−ブロモ−2,3,4 −トリフルオロベンゼン基準の選択率は74%であった。
【0016】
比較例1(3,4,5 −トリフルオロフェノールの製造)
実施例1に対してスルホランを使用しない以外は同様な条件で反応を行った。その結果、反応速度が低下し、3,4,5 −トリフルオロフェノールの収量は10.2gとなった。
【0017】
比較例2(3,4,5 −トリフルオロフェノールの製造)
実施例1に対し、塩基である水酸化カルシウム5.5gを添加して反応を行った。その結果、高沸点物の生成が増え、3,4,5 −トリフルオロフェノールの収量は8.8gとなった。
【0018】
【発明の効果】
本発明の方法によれば、トリフルオロフェノール類を既存の方法よりも高収率で有利に製造することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for efficiently producing trifluorophenols that can be important intermediates such as pharmaceuticals, agricultural chemicals, and liquid crystals.
[0002]
[Prior art]
Conventionally, as a method for producing fluorophenols, 1) a method of hydrolyzing fluoroaniline after diazotization [J.Am.Chem.Soc. , 61, 165 (1939)], 2) fluoroanisole by seaman reaction from aminoanisole And then hydrolyzing the methoxy group [Nikka 79, 1121 (1979)] 3) Reaction of polyfluorobenzenes with sodium methoxide in an aprotic polar solvent such as N, N-dimethylformamide To obtain fluoroanisole with one fluorine decreased, and then hydrolyze [JP-A-9-136853], 4) method to hydrolyze chlorofluorobenzene or bromofluorobenzene in the presence of a base [(1) J. Fluorine Chem. , 50, 377, (1990), (2) J. Org. Chem. , 26 , 4641, (1961)] and the like are known.
However, all of the above methods have problems. That is, the method 1) has a low yield (especially, this tendency tends to increase as the number of fluorines increases), and it is difficult to say that the method can be put into practical use, such as producing a large amount of waste. The method 2) is long in process, has problems such as difficulty in controlling by reaction heat, and in particular, it is extremely difficult to add three fluorine atoms. The method 3) has a good yield and is useful, but in the case of trifluorophenols, it has problems such as difficulty in obtaining tetrafluorobenzenes as raw materials. In the method 4), the yield is good when the number of fluorine is 1 to 2 (especially when the number is 1), but it is extremely lowered when the number of fluorine is 3.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a method capable of efficiently producing trifluorophenols useful as an intermediate compound.
[0004]
Thus, as a result of further earnest studies on the method 5), the present inventors have found a useful production method.
[0005]
[Means for Solving the Problems]
In the present invention, monobromotrifluorobenzene represented by the following general formula (I) is heated in a mixed solvent of water and an aprotic polar solvent in the presence of a copper compound catalyst to perform a hydrolysis reaction. Provides a method for producing trifluorophenols represented by the following general formula (II).
[0006]
[Chemical 3]
[0007]
[Formula 4]
[0008]
That is, the gist of the present invention resides in a method for producing trifluorophenols by hydrolyzing monobromotrifluorobenzenes.
As described above, a method of synthesizing phenols by hydrolyzing bromobenzenes in the presence of copper or a copper compound catalyst and a base compound is known. However, in our experience, in the case of trifluoro derivatives Under known conditions in this reaction, the yield was extremely reduced. The present inventors have found that the yield is remarkably improved by stopping the use of a base compound in the reaction and adding an aprotic polar solvent such as sulfolane, and have reached the present invention.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
In the specific implementation of the present invention, an autoclave or the like is charged with monobromotrifluorobenzenes represented by the general formula (I), a copper compound, water, and an aprotic polar solvent, and is stirred at a predetermined temperature at a predetermined temperature. Let react for hours. After completion of the reaction, the mixture is cooled to room temperature, the reaction product is taken out, and diluted hydrochloric acid and an organic solvent for extraction (for example, dichloromethane) are added and shaken. The organic phase is separated, and then the desired trifluorophenols are obtained by distillation.
[0010]
Although it does not specifically limit as a copper compound of a catalyst, Cuprous oxide and cupric oxide are suitable. In the case of copper bromide, copper chloride, and copper sulfate, the catalytic effect is small, and the effect of copper powder also tends to be small. Copper oxide is used in a molar ratio of 0.1 to 1.0, preferably 0.3 to 0.6, relative to monobromotrifluorobenzenes. If it is less than 0.1, the effect of addition is not recognized, and if it is more than 1.0, the reaction rate is no longer increased.
[0011]
As the aprotic polar solvent, sulfolane, dimethyl sulfoxide, or 1,3-dimethyl-2-imidazolidinone can be used, but sulfolane is particularly preferred because there is no side reaction excitation.
The aprotic polar solvent is used as a co-solvent with water, and the ratio thereof is 0.1 to 0.5, preferably 0.2 to 0.4, by weight. If it is less than 0.1, the effect of addition is not recognized, and if it is more than 0.5 , an increase in the reaction rate is no longer observed.
[0012]
The reaction temperature of the present invention is preferably 210 to 270 ° C.
The reaction time is suitably 3 to 10 hours.
[0013]
The monobromotrifluorobenzenes represented by the general formula (I) of the present invention have six types of isomers, but those that are relatively easily available are 1-bromo-3,4,5-trifluorobenzene and 1 -Bromo-2,3,4-trifluorobenzene. 3,4,5-trifluorophenol from 1-bromo-3,4,5-trifluorobenzene, 2,3,4-trifluorophenol from 1-bromo-2,3,4-trifluorobenzene Are obtained respectively.
[0014]
【Example】
EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.
Example 1 (Production of 3,4,5-trifluorophenol)
A 500 ml stainless steel autoclave was charged with 52.8 g (0.250 mol) of 1-bromo-3,4,5-trifluorobenzene, 10 g of cuprous oxide, 135 ml of water and 40 ml of sulfolane. The reaction was carried out at 210 ° C. for 5 hours under stirring. After the reaction, the autoclave was opened after cooling to room temperature, and the reaction product was transferred to a 1 liter beaker. The inside of the autoclave was washed with dichloromethane, and the washing solution was added to the beaker. Next, the mixture was transferred to a 1-liter separatory funnel, 150 ml of dichloromethane was added, and the mixture was allowed to stand after shaking to separate the organic phase. Subsequently, this organic phase was distilled to obtain 22.6 g of 3,4,5-trifluorophenol, and 13.1 g of 1-bromo-3,4,5-trifluorobenzene was recovered. The selectivity based on 1-bromo-3,4,5-trifluorobenzene was 81%.
[0015]
Example 2 (Production of 2,3,4-trifluorophenol)
The same procedure as in Example 1 was performed except that 1-bromo-2,3,4-trifluorobenzene was used instead of 1-bromo-3,4,5-trifluorobenzene. 20.7 g of 3,4,5-trifluorophenol was obtained, and 13.1 g of 1-bromo-2,3,4-trifluorobenzene was recovered. The selectivity based on 1-bromo-2,3,4-trifluorobenzene was 74%.
[0016]
Comparative Example 1 (Production of 3,4,5-trifluorophenol)
The reaction was carried out under the same conditions as in Example 1 except that sulfolane was not used. As a result, the reaction rate decreased and the yield of 3,4,5-trifluorophenol was 10.2 g.
[0017]
Comparative Example 2 (Production of 3,4,5-trifluorophenol)
The reaction was carried out by adding 5.5 g of calcium hydroxide as a base to Example 1. As a result, the production of high boilers increased, and the yield of 3,4,5-trifluorophenol was 8.8 g.
[0018]
【The invention's effect】
According to the method of the present invention, trifluorophenols can be advantageously produced in a higher yield than existing methods.
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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JP33095498A JP4034889B2 (en) | 1998-11-20 | 1998-11-20 | Process for producing trifluorophenols |
Applications Claiming Priority (1)
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JP33095498A JP4034889B2 (en) | 1998-11-20 | 1998-11-20 | Process for producing trifluorophenols |
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JP2000154159A JP2000154159A (en) | 2000-06-06 |
JP2000154159A5 JP2000154159A5 (en) | 2005-10-06 |
JP4034889B2 true JP4034889B2 (en) | 2008-01-16 |
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JP33095498A Expired - Fee Related JP4034889B2 (en) | 1998-11-20 | 1998-11-20 | Process for producing trifluorophenols |
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