JP4471081B2 - Method for producing p-fluorobenzaldehyde - Google Patents
Method for producing p-fluorobenzaldehyde Download PDFInfo
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- JP4471081B2 JP4471081B2 JP2003416630A JP2003416630A JP4471081B2 JP 4471081 B2 JP4471081 B2 JP 4471081B2 JP 2003416630 A JP2003416630 A JP 2003416630A JP 2003416630 A JP2003416630 A JP 2003416630A JP 4471081 B2 JP4471081 B2 JP 4471081B2
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- fluorobenzaldehyde
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- boron trifluoride
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- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 title claims description 34
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 46
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 229910015900 BF3 Inorganic materials 0.000 claims description 23
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 22
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims description 22
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 10
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 description 18
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 9
- CHLICZRVGGXEOD-UHFFFAOYSA-N 1-Methoxy-4-methylbenzene Chemical compound COC1=CC=C(C)C=C1 CHLICZRVGGXEOD-UHFFFAOYSA-N 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 8
- 238000006170 formylation reaction Methods 0.000 description 8
- PIKNVEVCWAAOMJ-UHFFFAOYSA-N 3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1 PIKNVEVCWAAOMJ-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229940077398 4-methyl anisole Drugs 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000003172 aldehyde group Chemical group 0.000 description 3
- BXILREUWHCQFES-UHFFFAOYSA-K aluminum;trichloride;hydrochloride Chemical compound [Al+3].Cl.[Cl-].[Cl-].[Cl-] BXILREUWHCQFES-UHFFFAOYSA-K 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000022244 formylation Effects 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PLISNXKNHRAEPS-UHFFFAOYSA-N 1-[chloro-(2-fluorophenyl)methyl]-2-fluorobenzene Chemical compound FC1=CC=CC=C1C(Cl)C1=CC=CC=C1F PLISNXKNHRAEPS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- -1 aromatic hydrocarbon carbon monoxide Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000001577 simple distillation Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、医薬、農薬原料中間体として有用なｐ−フルオロベンズアルデヒドの製造に関するものである。 The present invention relates to the production of p-fluorobenzaldehyde useful as an intermediate for raw materials for pharmaceuticals and agricultural chemicals.
塩化水素−塩化アルミニウム等を触媒として使用する、芳香族炭化水素の一酸化炭素によるホルミル化による芳香族アルデヒドの製造は、ガッターマン・コッホ反応としてよく知られている。しかしながらこの反応は、アルキル基等の電子供与性の置換基が結合した芳香族炭化水素の場合にはスムーズに進行するが、電子吸引性の置換基が結合している場合には、反応の進行が遅く、工業的に実施することは困難とされていた。
例えば、塩化アルミニウムに対して極少量の塩化水素を添加する触媒系において、フルオロベンゼンと一酸化炭素を反応させることによりｐ−フルオロベンズアルデヒドが得られることが開示されている（特許文献１参照）が、１８時間反応させても、使用した触媒の塩化アルミニウムベースの収率で約２４．１％、原料フルオロベンゼンベースの収率では３．４％と低く（実施例４参照）、また反応を促進すると記載されている４−メチルアニソールを添加しても、反応時間８９時間で、塩化アルミニウムのモル数から添加した４−メチルアニソールのモル数を差し引いたモル数ベース（４−メチルアニソールと塩化アルミニウムが１：１で錯体を形成すると考えて計算していると思われる）の収率で６４．３％、４−メチルアニソール分を差し引かない塩化アルミニウムベースで２９．７％、原料フルオロベンゼンベースでの収率では９．４％となっている。なお、特許文献１の実施例中では副生物については何も示されておらず、どのような副生物がどの位生成するかは不明である。
The production of aromatic aldehydes by formylation with aromatic hydrocarbon carbon monoxide using hydrogen chloride-aluminum chloride or the like as a catalyst is well known as the Guttermann-Koch reaction. However, this reaction proceeds smoothly in the case of an aromatic hydrocarbon to which an electron-donating substituent such as an alkyl group is bonded, but when the electron-withdrawing substituent is bonded, the reaction proceeds. However, it was considered to be difficult to implement industrially.
For example, it is disclosed that p-fluorobenzaldehyde can be obtained by reacting fluorobenzene and carbon monoxide in a catalyst system in which a very small amount of hydrogen chloride is added to aluminum chloride (see Patent Document 1). Even after 18 hours of reaction, the yield of the catalyst used was about 24.1% based on aluminum chloride and 3.4% based on the raw material fluorobenzene (see Example 4). Then, even when 4-methylanisole described is added, the reaction time is 89 hours, and the mole number is based on the number of moles of aluminum chloride minus the number of moles of 4-methylanisole added (4-methylanisole and aluminum chloride). In the yield of 64.3%, 4-methylanisole content) 29.7 percent aluminum base chloride not subtracted, which is 9.4% in the yield of the raw material fluorobenzene base. In addition, in the Example of patent document 1, nothing is shown about a by-product, and it is unclear what by-product and how much is produced.
また、同じく塩化アルミニウム−塩化水素触媒系にて、フルオロベンゼンと一酸化炭素とを反応温度４５℃から１００℃で反応させることにより、ｐ−フルオロベンズアルデヒドが得られることが開示されている（特許文献２参照）。この場合、収率は具体的な数値では示されていないが、図５から、最も原単位的に良好とされている塩化アルミニウムとフルオロベンゼン重量比５０：５０の場合、塩化アルミニウムベースの収率で約７４％、フルオロベンゼンベースで転化率約５８％、選択率９１．１％、収率約５３％であることが読みとれる。なお、特許文献２には、主な副生物としてｏ−フルオロベンズアルデヒド、ｍ−フルオロベンズアルデヒド、クロロ−ビス（フルオロフェニル）メタン、およびオリゴマーが生成し、また、フルオロベンズアルデヒド３異性体間の生成比として、ｏ−：ｍ−：ｐ−＝１．８：０．２：９８．３であると記載されている。
これらのように、塩化水素−塩化アルミニウム系を触媒として用いる場合、ホルミル化反応終了後に生成物と触媒を分離するために、通常、反応混合物を水で処理するので、触媒の再生が非常に困難である。また廃棄する場合にも加水分解により大量の廃棄物が発生し、処理費用が嵩むという課題もある。その観点も含めて考えると、上記２件とも不十分な反応成績である。
Further, it is disclosed that p-fluorobenzaldehyde can be obtained by reacting fluorobenzene and carbon monoxide at a reaction temperature of 45 ° C. to 100 ° C. in an aluminum chloride-hydrogen chloride catalyst system (Patent Document). 2). In this case, the yield is not shown by a specific numerical value, but from FIG. 5, when the weight ratio of aluminum chloride and fluorobenzene, which is considered to be the best in terms of basic unit, is 50:50, the yield based on aluminum chloride. About 74%, conversion based on fluorobenzene is about 58%, selectivity is 91.1%, and yield is about 53%. In Patent Document 2, o-fluorobenzaldehyde, m-fluorobenzaldehyde, chloro-bis (fluorophenyl) methane, and oligomers are produced as main by-products, and the production ratio among the three isomers of fluorobenzaldehyde is as follows. , O-: m-: p- = 1.8: 0.2: 98.3.
As described above, when a hydrogen chloride-aluminum chloride system is used as a catalyst, the reaction mixture is usually treated with water in order to separate the product and the catalyst after completion of the formylation reaction. Therefore, it is very difficult to regenerate the catalyst. It is. Further, when it is discarded, there is a problem that a large amount of waste is generated due to hydrolysis and the processing cost is increased. Considering the viewpoint, the above two cases are insufficient reaction results.
また、ガッターマン・コッホ反応以外の方法として、フッ化水素、三フッ化ホウ素触媒にてフルオロベンゼンとギ酸メチルを反応させることにより、ｐ−フルオロベンズアルデヒドが得られることが開示されている（特許文献３参照）が、この場合、反応副生物としてメタノールが生成すると考えられ、このものとフッ化水素、三フッ化ホウ素との分離が困難であるという問題が残っている。
また、フッ化水素の存在下でウロトロピンとフルオロベンゼンを反応させることにより、ｐ−フルオロベンズアルデヒドが得られることが開示されている（特許文献４参照）が、同時にｏ−フルオロベンズアルデヒドも相当量副生し、また収率もフルオロベンズアルデヒド２異性体合計で約３０％程度でありかなり低い。
Moreover, it is disclosed that p-fluorobenzaldehyde can be obtained by reacting urotropin and fluorobenzene in the presence of hydrogen fluoride (see Patent Document 4), but at the same time, a considerable amount of o-fluorobenzaldehyde is also produced as a by-product. In addition, the yield is about 30% in terms of the total of the two fluorobenzaldehyde isomers, which is quite low.
このように、これまでに知られている方法では、フルオロベンゼンに直接アルデヒド基を導入してｐ−フルオロベンズアルデヒドを工業的に製造するには、収率が低い問題や、または触媒との分離が困難であるために触媒の再使用ができない等、コスト的に不利になる等の問題が存在していた。
本発明の目的は、フルオロベンゼンを原料として用い、これに直接アルデヒド基を導入してｐ−フルオロベンズアルデヒドを工業的に有利な方法で製造する方法を提案することにある。
As described above, in the known methods, in order to industrially produce p-fluorobenzaldehyde by directly introducing an aldehyde group into fluorobenzene, there is a problem of low yield or separation from a catalyst. There are problems such as cost disadvantages such as difficulty in reusing the catalyst due to difficulty.
An object of the present invention is to propose a method for producing p-fluorobenzaldehyde by an industrially advantageous method by using fluorobenzene as a raw material and directly introducing an aldehyde group thereto.
本発明者らは、フルオロベンゼンに直接アルデヒド基を導入してｐ−フルオロベンズアルデヒドを製造する方法を鋭意検討した結果、触媒としてフッ化水素、三フッ化ホウ素を用いてフルオロベンゼンと一酸化炭素を反応させることにより、極めて高い選択率、および高い原料フルオロベンゼン転化率で高純度のｐ−フルオロベンズアルデヒドが得られ、しかも、触媒の回収・再使用が可能であることから、工業的に非常に有利であることを見い出し、本発明に到達した。
即ち本発明は、フッ化水素および三フッ化ホウ素の存在下、フルオロベンゼンと一酸化炭素を反応させることを特徴とする、ｐ−フルオロベンズアルデヒドの製造方法である。
As a result of intensive studies on a method for producing p-fluorobenzaldehyde by directly introducing an aldehyde group into fluorobenzene, the inventors of the present invention have used fluorofluoride and carbon monoxide as catalysts using hydrogen fluoride and boron trifluoride. By carrying out the reaction, highly pure p-fluorobenzaldehyde can be obtained with a very high selectivity and a high raw material fluorobenzene conversion rate, and the catalyst can be recovered and reused. As a result, the present invention has been reached.
That is, the present invention is a method for producing p-fluorobenzaldehyde characterized by reacting fluorobenzene and carbon monoxide in the presence of hydrogen fluoride and boron trifluoride.
本発明の方法により、フルオロベンゼンを原料として一段の反応で、高純度のｐ−フルオロベンズアルデヒドを、収率良く、安価に製造することが可能である。 By the method of the present invention, it is possible to produce high-purity p-fluorobenzaldehyde with high yield and low cost by a one-step reaction using fluorobenzene as a raw material.
本発明で原料として用いられるフルオロベンゼンは、ベンゼンの水素原子の１つをフッ素で置換したモノフルオロベンゼンであり、通常入手できるものであれば特に問題はない。 The fluorobenzene used as a raw material in the present invention is monofluorobenzene obtained by substituting one hydrogen atom of benzene with fluorine, and there is no particular problem as long as it is usually available.
本発明において、フルオロベンゼンと一酸化炭素を反応（ホルミル化反応）させる際に触媒としてフッ化水素および三フッ化ホウ素を使用することが重要である。この触媒を用いて反応を行うことにより、常温よりも低い反応温度下においてもｐ−フルオロベンズアルデヒドが得られ、生成するｐ−フルオロベンズアルデヒドがさらに反応して生成する副生物の生成が極めて少なくなる。また、フッ化水素および三フッ化ホウ素を触媒として使用することにより、ｐ−フルオロベンズアルデヒド異性体のｏ−フルオロベンズアルデヒドは極めて微量しか生成せず、またもう一つの異性体であるｍ−フルオロベンズアルデヒドにおいては全く生成が認められなくなる。 In the present invention, it is important to use hydrogen fluoride and boron trifluoride as a catalyst when reacting fluorobenzene and carbon monoxide (formylation reaction). By performing the reaction using this catalyst, p-fluorobenzaldehyde is obtained even at a reaction temperature lower than room temperature, and the production of by-products generated by further reaction of the generated p-fluorobenzaldehyde is extremely reduced. In addition, by using hydrogen fluoride and boron trifluoride as catalysts, the p-fluorobenzaldehyde isomer, o-fluorobenzaldehyde, is produced in a very small amount, and in another isomer, m-fluorobenzaldehyde. No generation is allowed.
本発明において使用するフッ化水素の量は、原料のフルオロベンゼン１モルに対して、５．０モル以上が好ましく、７．０モル以上がより好ましい。フッ化水素の使用量が多い方が原料転化率が高くなるが、あまり多量に使用すると装置の容積効率が低下し、かつ回収するべきフッ化水素の量が増加するため、その上限は適宜選択され、通常３０．０モル以下を使用する。 The amount of hydrogen fluoride used in the present invention is preferably 5.0 mol or more, and more preferably 7.0 mol or more with respect to 1 mol of the raw material fluorobenzene. The higher the amount of hydrogen fluoride used, the higher the raw material conversion rate. However, if the amount used is too large, the volumetric efficiency of the device will decrease and the amount of hydrogen fluoride to be recovered will increase. Usually, 30.0 mol or less is used.
一方、三フッ化ホウ素の使用量は、原料のフルオロベンゼン１モルに対して１．３モル以上５．０モル以下が好ましく、より好ましくは１．５モル以上３．５モル以下である。使用する三フッ化ホウ素の量が１．３モルより少ない場合には、ホルミル化反応速度が極端に遅くなり、工業的に不利となる。また、三フッ化ホウ素の量を、５．０モルを超えて使用することも可能ではあるが、その場合、一酸化炭素を供給する前でかなり圧力が上昇してしまい、さらに一酸化炭素で加圧するため、かなり高圧の反応器が必要になるため好ましくない。 On the other hand, the amount of boron trifluoride used is preferably 1.3 mol or more and 5.0 mol or less, more preferably 1.5 mol or more and 3.5 mol or less with respect to 1 mol of fluorobenzene as a raw material. When the amount of boron trifluoride used is less than 1.3 mol, the formylation reaction rate becomes extremely slow, which is industrially disadvantageous. Moreover, although it is possible to use the amount of boron trifluoride exceeding 5.0 mol, in that case, the pressure is considerably increased before the carbon monoxide is supplied. Since pressurization requires a considerably high pressure reactor, it is not preferable.
反応の温度は、望ましくない副反応を抑えるための重要な因子であり、本発明においては好ましくは０℃以下、より好ましくは−１０℃以下で実施される。前述したように、触媒としてフッ化水素と三フッ化ホウ素を用いることにより、このような低温下でもフルオロベンゼンのホルミル化反応が十分進行し、結果として副生物の生成を極端に少なくすることができる。なお、極端な低温は必要ではなく、フルオロベンゼンの融点である−４２℃以上が選択される。 The temperature of the reaction is an important factor for suppressing undesirable side reactions. In the present invention, the reaction temperature is preferably 0 ° C. or lower, more preferably −10 ° C. or lower. As described above, by using hydrogen fluoride and boron trifluoride as a catalyst, the formylation reaction of fluorobenzene proceeds sufficiently even at such a low temperature, and as a result, the generation of by-products can be extremely reduced. it can. Note that an extremely low temperature is not necessary, and −42 ° C. or higher, which is the melting point of fluorobenzene, is selected.
ホルミル化反応における一酸化炭素分圧としては好ましくは０．５ＭＰａ以上、より好ましくは０．７ＭＰａ以上の圧力が収率の面で好ましいが、３ＭＰａを超える圧力は経済的にも得策ではなく、不必要である。 The carbon monoxide partial pressure in the formylation reaction is preferably 0.5 MPa or more, more preferably 0.7 MPa or more in terms of yield. However, a pressure exceeding 3 MPa is not economically advantageous and is not good. is necessary.
ホルミル化反応後には、ｐ−フルオロベンズアルデヒド・フッ化水素・三フッ化ホウ素錯体溶液が得られる。得られたｐ−フルオロベンズアルデヒド・フッ化水素・三フッ化ホウ素錯体溶液は、例えば適当な分解助剤の存在下で加熱分解することにより、生成物であるｐ−フルオロベンズアルデヒドの分解助剤溶液（未反応のフルオロベンゼンを含む）と触媒のフッ化水素、三フッ化ホウ素に分離することができる。分離されたフッ化水素、三フッ化ホウ素は廃棄する必要がなく、触媒として反応に再使用することができる。また、ｐ−フルオロベンズアルデヒドの分解助剤溶液は未反応のフルオロベンゼン以外の副生物（特にｐ−フルオロベンズアルデヒドの異性体）をほとんど含んでいないため、簡単な蒸留等により精製され、目的とするｐ−フルオロベンズアルデヒドを高純度で得ることができる。 After the formylation reaction, a p-fluorobenzaldehyde / hydrogen fluoride / boron trifluoride complex solution is obtained. The obtained p-fluorobenzaldehyde / hydrogen fluoride / boron trifluoride complex solution is decomposed by heating in the presence of a suitable decomposition aid, for example, to thereby decompose the product p-fluorobenzaldehyde decomposition aid solution ( (Including unreacted fluorobenzene) and catalyst hydrogen fluoride and boron trifluoride. The separated hydrogen fluoride and boron trifluoride do not need to be discarded and can be reused in the reaction as a catalyst. In addition, since the decomposition aid solution for p-fluorobenzaldehyde contains almost no by-products other than unreacted fluorobenzene (particularly, isomers of p-fluorobenzaldehyde), it is purified by simple distillation or the like, and the target p -Fluorobenzaldehyde can be obtained with high purity.
以下、実施例により、本発明を具体的に説明する。ただし、本発明はこれらの実施例により何ら制限されるものではない。 Hereinafter, the present invention will be described specifically by way of examples. However, this invention is not restrict | limited at all by these Examples.
＜実施例１＞
攪拌機と上部に３個の入口ノズル、底部に１個の出口ノズルを備え、ジャケットにより内部温度を制御できる５００ｍｌのオートクレーブをホルミル化反応器として使用した。
ジャケットに冷媒を流し、−２０℃以下に冷却したオートクレーブにフッ化水素１５０ｇ（７．５モル）およびフルオロベンゼン７２．１ｇ（０．７５モル）を仕込んだ。その後、撹拌させながら、温度が−２０℃を超えないように調整しながら、三フッ化ホウ素１０１．７ｇ（１．５モル）を加えた。
三フッ化ホウ素を加えた後、オートクレーブ内の温度を−２５℃に冷却し、その温度を保ったまま一酸化炭素により２ＭＰａまで昇圧した。温度−２５℃、圧力２ＭＰａを保ちながら１時間撹拌した後、オートクレーブ内の反応混合液を氷水中に抜液した。抜液したものにトルエンを加え、良く振り混ぜた後、油層を分液した。得られた油層部を水洗した後、ガスクロマトグラフィーにより分析したところ、フルオロベンゼン転化率３７．１モル％、ｐ−フルオロベンズアルデヒド選択率９９．８モル％の結果であった。なお、ｐ−フルオロベンズアルデヒドとｏ−フルオロベンズアルデヒドの生成比は９９．９６：０．０４であり、ｍ−フルオロベンズアルデヒドは検出されなかった。
<Example 1>
A 500 ml autoclave equipped with a stirrer and three inlet nozzles at the top and one outlet nozzle at the bottom and whose internal temperature can be controlled by a jacket was used as the formylation reactor.
A refrigerant was passed through the jacket, and 150 g (7.5 mol) of hydrogen fluoride and 72.1 g (0.75 mol) of fluorobenzene were charged into an autoclave cooled to −20 ° C. or lower. Thereafter, 101.7 g (1.5 mol) of boron trifluoride was added while adjusting the temperature not to exceed −20 ° C. while stirring.
After adding boron trifluoride, the temperature in the autoclave was cooled to −25 ° C., and the pressure was increased to 2 MPa with carbon monoxide while maintaining the temperature. After stirring for 1 hour while maintaining a temperature of -25 ° C and a pressure of 2 MPa, the reaction mixture in the autoclave was drained into ice water. Toluene was added to the drained liquid, and after shaking well, the oil layer was separated. The obtained oil layer was washed with water and analyzed by gas chromatography. The result was that the fluorobenzene conversion was 37.1 mol% and the p-fluorobenzaldehyde selectivity was 99.8 mol%. The production ratio of p-fluorobenzaldehyde and o-fluorobenzaldehyde was 99.96: 0.04, and m-fluorobenzaldehyde was not detected.
＜実施例２＞
フッ化水素の仕込量を１００ｇ（５．０モル）、フルオロベンゼンの仕込量を９６．１ｇ（１．０モル）に、三フッ化ホウ素の仕込量を１３５．６ｇ（２．０モル）に変えた以外は実施例１と同様の方法で反応と反応混合液の処理を行った。得られた油層部のガスクロマトグラフィー分析の結果、フルオロベンゼン転化率２０．３モル％、ｐ−フルオロベンズアルデヒド選択率９９．８モル％の結果であった。なお、ｐ−フルオロベンズアルデヒドとｏ−フルオロベンズアルデヒドの生成比は９９．９６：０．０４であり、ｍ−フルオロベンズアルデヒドは検出されなかった。
<Example 2>
The amount of hydrogen fluoride charged is 100 g (5.0 mol), the amount of fluorobenzene charged is 96.1 g (1.0 mol), and the amount of boron trifluoride charged is 135.6 g (2.0 mol). Except for the change, the reaction and the reaction mixture were processed in the same manner as in Example 1. As a result of gas chromatography analysis of the obtained oil layer portion, it was found that the conversion rate of fluorobenzene was 20.3% mol% and the selectivity for p-fluorobenzaldehyde was 99.8 mol%. The production ratio of p-fluorobenzaldehyde and o-fluorobenzaldehyde was 99.96: 0.04, and m-fluorobenzaldehyde was not detected.
＜実施例３＞
三フッ化ホウ素の仕込量を１５２．６ｇ（２．２５モル）に、反応温度を−３０℃に、反応時間を３時間にした以外は実施例１と同じ方法で反応と反応混合液の処理を行った。得られた油層部のガスクロマトグラフィー分析の結果、フルオロベンゼン転化率７１．６モル％、ｐ−フルオロベンズアルデヒド選択率９９．９モル％の結果であった。なお、ｐ−フルオロベンズアルデヒドとｏ−フルオロベンズアルデヒドの生成比は９９．９７：０．０３であり、ｍ−フルオロベンズアルデヒドは検出されなかった。
<Example 3>
Treatment of the reaction and reaction mixture in the same manner as in Example 1 except that the amount of boron trifluoride charged was 152.6 g (2.25 mol), the reaction temperature was −30 ° C., and the reaction time was 3 hours. Went. As a result of gas chromatography analysis of the obtained oil layer portion, it was found that the conversion rate of fluorobenzene was 71.6 mol% and the selectivity for p-fluorobenzaldehyde was 99.9 mol%. The production ratio of p-fluorobenzaldehyde and o-fluorobenzaldehyde was 99.97: 0.03, and m-fluorobenzaldehyde was not detected.
＜実施例４＞
フッ化水素の仕込量を２００ｇ（１０．０モル）、フルオロベンゼンの仕込量を４８．１ｇ（０．５モル）、三フッ化ホウ素の仕込量を１０１．７ｇ（１．５モル）にし、−３０℃にて実施例１と同様の操作にて５時間反応させた。実施例１と同様の操作にて反応混合液の処理を行い、得られた油層部をガスクロマトグラフィーで分析したところ、フルオロベンゼンの転化率９０．６モル％、ｐ−フルオロベンズアルデヒド選択率９９．９モル％の結果であった。なお、ｐ−フルオロベンズアルデヒドとｏ−フルオロベンズアルデヒドの生成比は９９．９７：０．０３であり、ｍ−フルオロベンズアルデヒドは検出されなかった。
<Example 4>
The amount of hydrogen fluoride charged is 200 g (10.0 mol), the amount of fluorobenzene charged is 48.1 g (0.5 mol), the amount of boron trifluoride charged is 101.7 g (1.5 mol), The reaction was carried out at −30 ° C. for 5 hours in the same manner as in Example 1. The reaction mixture was treated in the same manner as in Example 1, and the obtained oil layer was analyzed by gas chromatography. As a result, the conversion rate of fluorobenzene was 90.6 mol%, and the p-fluorobenzaldehyde selectivity was 99. The result was 9 mol%. The production ratio of p-fluorobenzaldehyde and o-fluorobenzaldehyde was 99.97: 0.03, and m-fluorobenzaldehyde was not detected.
＜実施例５＞
フッ化水素の仕込量を２００ｇ（１０．０モル）、フルオロベンゼンの仕込量を４８．１ｇ（０．５モル）、三フッ化ホウ素の仕込量を６７．８ｇ（１．０モル）にし、２０℃の反応温度にて実施例１と同様の操作にて３時間反応を行った。実施例１と同様の操作にて反応混合液の処理を行い、得られた油層部のガスクロマトグラフィー分析の結果、フルオロベンゼン転化率は３０モル％であった。なおｐ−フルオロベンズアルデヒド選択率は９７．０モル％であり、ｐ−フルオロベンズアルデヒドと原料のフルオロベンゼンが反応して生成したと考えられる高沸分が生成していることが確認された。
<Example 5>
The amount of hydrogen fluoride charged is 200 g (10.0 mol), the amount of fluorobenzene charged is 48.1 g (0.5 mol), the amount of boron trifluoride charged is 67.8 g (1.0 mol), The reaction was carried out at the reaction temperature of 20 ° C. for 3 hours in the same manner as in Example 1. The reaction mixture was treated in the same manner as in Example 1. As a result of gas chromatographic analysis of the obtained oil layer portion, the fluorobenzene conversion was 30 mol%. The selectivity for p-fluorobenzaldehyde was 97.0 mol%, and it was confirmed that a high-boiling fraction considered to be produced by the reaction of p-fluorobenzaldehyde and the raw material fluorobenzene was produced.
本発明により得られる高純度のｐ−フルオロベンズアルデヒドは、医薬および農薬の原料や中間体として極めて有用である。 The high-purity p-fluorobenzaldehyde obtained by the present invention is extremely useful as a raw material or intermediate for pharmaceuticals and agricultural chemicals.
Claims (1)
In the method for producing p-fluorobenzaldehyde in which fluorobenzene and carbon monoxide are reacted in the presence of hydrogen fluoride and boron trifluoride, the amount of hydrogen fluoride and boron trifluoride used is 1 mol of fluorobenzene. Hydrogen fluoride is 5.0 mol or more and 30.0 mol or less, boron trifluoride is 1.3 mol or more and 5.0 mol or less, and the reaction temperature is −42 ° C. or more and 0 ° C. or less. A process for producing p-fluorobenzaldehyde.
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| JP2003416630A JP4471081B2 (en) | 2003-12-15 | 2003-12-15 | Method for producing p-fluorobenzaldehyde |
| EP04106385.0A EP1544189B1 (en) | 2003-12-15 | 2004-12-08 | Method for producing halogen-substituted aromatic aldehydes |
| ES04106385.0T ES2438968T3 (en) | 2003-12-15 | 2004-12-08 | Production procedure of halogen substituted aromatic aldehydes |
| KR1020040105556A KR101136640B1 (en) | 2003-12-15 | 2004-12-14 | Method for producing halogen-substituted aromatic aldehyde |
| US11/011,136 US7241925B2 (en) | 2003-12-15 | 2004-12-15 | Method for producing halogen-substituted aromatic aldehyde |
| CNB2004100821048A CN100526278C (en) | 2003-12-15 | 2004-12-15 | Method for producing halogen-substituted aromatic aldehyde |
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