JP2012180326A - METHOD FOR PRODUCING p-IODOPHENOL - Google Patents
METHOD FOR PRODUCING p-IODOPHENOL Download PDFInfo
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- JP2012180326A JP2012180326A JP2011045400A JP2011045400A JP2012180326A JP 2012180326 A JP2012180326 A JP 2012180326A JP 2011045400 A JP2011045400 A JP 2011045400A JP 2011045400 A JP2011045400 A JP 2011045400A JP 2012180326 A JP2012180326 A JP 2012180326A
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- iodophenol
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- phenol
- iodine monochloride
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- VSMDINRNYYEDRN-UHFFFAOYSA-N 4-iodophenol Chemical compound OC1=CC=C(I)C=C1 VSMDINRNYYEDRN-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 59
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 44
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000007864 aqueous solution Substances 0.000 claims abstract description 29
- 239000000243 solution Substances 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- -1 aliphatic acetates Chemical class 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 239000007810 chemical reaction solvent Substances 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 238000000151 deposition Methods 0.000 claims 1
- 239000006227 byproduct Substances 0.000 abstract description 11
- 238000001816 cooling Methods 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 6
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 229910052740 iodine Inorganic materials 0.000 description 12
- 239000011630 iodine Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 5
- 238000004811 liquid chromatography Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 5
- 235000019345 sodium thiosulphate Nutrition 0.000 description 5
- 230000002194 synthesizing effect Effects 0.000 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- 239000001116 FEMA 4028 Substances 0.000 description 4
- 229960004853 betadex Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- KQDJTBPASNJQFQ-UHFFFAOYSA-N 2-iodophenol Chemical compound OC1=CC=CC=C1I KQDJTBPASNJQFQ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- DAHRRUMUNVQEOB-UHFFFAOYSA-N 2,4-diiodophenol Chemical compound OC1=CC=C(I)C=C1I DAHRRUMUNVQEOB-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VNQABZCSYCTZMS-UHFFFAOYSA-N Orthoform Chemical compound COC(=O)C1=CC=C(O)C(N)=C1 VNQABZCSYCTZMS-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000000361 pesticidal effect Effects 0.000 description 1
- 235000009518 sodium iodide Nutrition 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)
Abstract
Description
本発明は、各種化合物の合成原料や、医薬・農薬中間体合成試薬として有用な物質であるｐ−ヨードフェノールの製造方法に関する。 The present invention relates to a method for producing p-iodophenol, which is a material useful as a raw material for synthesizing various compounds and a pharmaceutical / pesticidal intermediate synthesis reagent.
従来、ｐ−ヨードフェノールは、フェノールをアルカリ性溶液中でヨウ素と反応させる方法で製造されていた。通常、フェノールをヨウ素化すると、そのオルト−パラ配向性によりパラ体／オルト体の比率が７０／３０となる。 Conventionally, p-iodophenol has been produced by a method in which phenol is reacted with iodine in an alkaline solution. Generally, when phenol is iodinated, the ratio of para / ortho is 70/30 due to its ortho-para orientation.
そこで、パラ体の収率を向上させるために、アルカリ性雰囲気にてフェノールとヨウ素とを反応させる際に、β−シクロデキストリンの存在下で反応させて、ｐ−ヨードフェノールを製造する方法が知られている。この製造方法では、β−シクロデキストリン存在下で温度−５℃〜２℃にてフェノールのアルカリ水溶液中にヨウ素を滴下すると特に好ましく、そのパラ体／オルト体の比率は最高で９６／４である（例えば、特許文献１参照。）。 Therefore, a method for producing p-iodophenol by reacting in the presence of β-cyclodextrin when phenol and iodine are reacted in an alkaline atmosphere in order to improve the yield of the para-form is known. ing. In this production method, it is particularly preferable that iodine is dropped into an alkaline aqueous solution of phenol in the presence of β-cyclodextrin at a temperature of −5 ° C. to 2 ° C., and the maximum para / ortho ratio is 96/4. (For example, refer to Patent Document 1).
ここで、ｐ−ヨードフェノールは、種々の化合物の合成原料として用いられ、特に医薬や農薬の合成原料として用いられる場合には、パラ体／オルト体の比率が９９／１である高純度品が要求されることが少なくない。このため、精製を行うことにより、パラ体／オルト体の比率を高めてｐ−ヨードフェノールを高純度にする必要がある。 Here, p-iodophenol is used as a raw material for synthesizing various compounds. In particular, when it is used as a raw material for synthesizing pharmaceuticals and agricultural chemicals, a high-purity product having a para / ortho ratio of 99/1 is used. It is often requested. For this reason, it is necessary to increase the ratio of para-form / ortho-form to make p-iodophenol highly pure by performing purification.
しかしながら、パラ体／オルト体の比率が９６／４であるｐ−ヨードフェノールであっても、通常の精製手段では容易に純度を向上できず、精製工程を繰り返すことにより、ｐ−ヨードフェノールの純度を要求される純度にする必要がある。 However, even in the case of p-iodophenol having a para / ortho ratio of 96/4, the purity cannot be easily improved by ordinary purification means, and the purity of p-iodophenol can be improved by repeating the purification step. It is necessary to achieve the required purity.
このように精製工程を繰り返すと、収率が低下するとともに、工程数が多くなるためコストが上昇してしまう。 If the purification process is repeated in this manner, the yield decreases and the number of processes increases, resulting in an increase in cost.
そこで、高選択的にｐ−ヨードフェノールを合成する方法として、ヨウ素を予めβ−シクロデキストリンに包接させてヨウ素−β−シクロデキストリン包接化合物（以下ＢＣＤＩという。）とし、アルカリ水溶液中でフェノールとＢＣＤＩとを反応させる方法が知られている。この方法で得られるｐ−ヨードフェノールのパラ体／オルト体比は最高で１００／０である（例えば、特許文献２参照。）。 Therefore, as a method of highly selectively synthesizing p-iodophenol, iodine is previously included in β-cyclodextrin to form an iodine-β-cyclodextrin inclusion compound (hereinafter referred to as BCDI), and phenol in an alkaline aqueous solution. There is known a method of reacting BCI with BCDI. The maximum para-ortho-ratio of p-iodophenol obtained by this method is 100/0 (see, for example, Patent Document 2).
しかしながら、上述の特許文献１および特許文献２に記載されたｐ−ヨードフェノールの製造方法では、酸化剤を用いていないため、投入されるヨウ素の約１／２しか反応に寄与せず、残りのヨウ素はヨウ素イオンになる。すなわち、基本的には[化１]に示すように反応が進行し、投入したヨウ素の約半分しか反応に寄与せず、残りの半分はヨウ化ナトリウムになってしまう。 However, in the method for producing p-iodophenol described in Patent Document 1 and Patent Document 2 described above, since no oxidizing agent is used, only about 1/2 of the iodine added contributes to the reaction, and the remaining Iodine becomes iodine ions. That is, the reaction basically proceeds as shown in [Chemical Formula 1], and only about half of the added iodine contributes to the reaction, and the other half becomes sodium iodide.
したがって、特許文献１および特許文献２に記載されたｐ−ヨードフェノールの製造方法では、ヨウ素を効率的に反応に用いることができず、原材料費が上昇してしまい、効率的にｐ−ヨードフェノールを製造できない問題が考えられる。 Therefore, in the method for producing p-iodophenol described in Patent Document 1 and Patent Document 2, iodine cannot be used efficiently in the reaction, and the raw material cost increases, so that p-iodophenol is efficiently used. There may be a problem that cannot be manufactured.
本発明はこのような点に鑑みなされたもので、効率的にｐ−ヨードフェノールを製造できるｐ−ヨードフェノールの製造方法を提供することを目的とする。 This invention is made | formed in view of such a point, and it aims at providing the manufacturing method of p-iodophenol which can manufacture p-iodophenol efficiently.
請求項１に記載されたｐ−ヨードフェノールの製造方法は、フェノールと一塩化ヨウ素水溶液とを反応させる反応工程を具備したものである。 The method for producing p-iodophenol described in claim 1 comprises a reaction step of reacting phenol with iodine monochloride aqueous solution.
請求項２に記載されたｐ−ヨードフェノールの製造方法は、請求項１記載のｐ−ヨードフェノールの製造方法において、一塩化ヨウ素水溶液の一塩化ヨウ素は、フェノール１モルに対して０．５モル〜１．５モルであるものである。 The method for producing p-iodophenol according to claim 2 is the method for producing p-iodophenol according to claim 1, wherein iodine monochloride in an aqueous solution of iodine monochloride is 0.5 mol per mol of phenol. It is -1.5 mol.
請求項３に記載されたｐ−ヨードフェノールの製造方法は、請求項１または２に記載されたｐ−ヨードフェノールの製造方法において、反応工程では、水と混和しない有機溶媒を反応溶媒に用いるものである。 The method for producing p-iodophenol according to claim 3 is the method for producing p-iodophenol according to claim 1 or 2, wherein an organic solvent immiscible with water is used as a reaction solvent in the reaction step. It is.
請求項４に記載されたｐ−ヨードフェノールの製造方法は、請求項３に記載されたｐ−ヨードフェノールの製造方法において、有機溶媒は、炭素数６〜１０の脂肪族炭化水素、炭素数４〜６の脂肪族酢酸エステル類、炭素数４〜８の脂肪族エーテル類のいずれかであるものである。 The method for producing p-iodophenol according to claim 4 is the method for producing p-iodophenol according to claim 3, wherein the organic solvent is an aliphatic hydrocarbon having 6 to 10 carbon atoms, carbon number 4 -6 aliphatic acetates or C4-8 aliphatic ethers.
請求項５に記載されたｐ−ヨードフェノールの製造方法は、請求項１ないし４のいずれか記載のｐ−ヨードフェノールの製造方法において、反応工程後に、この反応工程で得られた反応液を反応温度以下に冷却してｐ−ヨードフェノールを析出させる結晶化工程を具備し、反応工程から結晶化工程までを同一反応容器で行うものである。 The method for producing p-iodophenol described in claim 5 is the method for producing p-iodophenol according to any one of claims 1 to 4, wherein the reaction solution obtained in this reaction step is reacted after the reaction step. It comprises a crystallization step in which p-iodophenol is precipitated by cooling to below the temperature, and the reaction step to the crystallization step are carried out in the same reaction vessel.
請求項１に記載された発明によれば、反応工程にてフェノールと一塩化ヨウ素水溶液を反応させるため、ヨウ素を効率的に反応に用いることができるので、効率的にｐ−ヨードフェノールを製造できる。 According to the invention described in claim 1, since phenol and iodine monochloride aqueous solution are reacted in the reaction step, iodine can be efficiently used for the reaction, and therefore p-iodophenol can be efficiently produced. .
請求項２に記載された発明によれば、目的物以外の副生成物の生成を抑制できるので、効率的にｐ−ヨードフェノールを製造できる。 According to the invention described in claim 2, since the production of by-products other than the target product can be suppressed, p-iodophenol can be produced efficiently.
請求項３に記載された発明によれば、有機溶媒に目的物以外の副生成物を選択的に抽出できるので、効率的にｐ−ヨードフェノールを製造できる。 According to the invention described in claim 3, by-products other than the target product can be selectively extracted into the organic solvent, so that p-iodophenol can be produced efficiently.
請求項４に記載された発明によれば、炭素数６〜１０の脂肪族炭化水素、炭素数４〜６の脂肪族酢酸エステル類、炭素数４〜８の脂肪族エーテル類のいずれかに目的物以外の副生成物を選択的に抽出できるので、効率的にｐ−ヨードフェノールを製造できる。 According to the invention described in claim 4, the object is any one of an aliphatic hydrocarbon having 6 to 10 carbon atoms, an aliphatic acetate ester having 4 to 6 carbon atoms, and an aliphatic ether having 4 to 8 carbon atoms. Since a by-product other than the product can be selectively extracted, p-iodophenol can be produced efficiently.
請求項５に記載された発明によれば、特殊な工程を必要とせず、容易にｐ−ヨードフェノールを単離できるので、容易にｐ−ヨードフェノールを製造できる。 According to the invention described in claim 5, since p-iodophenol can be easily isolated without requiring a special step, p-iodophenol can be easily produced.
以下、本発明の一実施の形態について詳細に説明する。 Hereinafter, an embodiment of the present invention will be described in detail.
ｐ−ヨードフェノールを製造する際には、フェノールと一塩化ヨウ素水溶液とを反応させる。 When producing p-iodophenol, phenol and iodine monochloride aqueous solution are reacted.
この反応工程において、一塩化ヨウ素水溶液は、５質量％以上５０質量％の一塩化ヨウ素水溶液が用いられることが好ましいが、濃度は適宜設定できる。 In this reaction step, the iodine monochloride aqueous solution is preferably 5% by mass or more and 50% by mass of iodine monochloride aqueous solution, but the concentration can be appropriately set.
また、反応工程では、一塩化ヨウ素水溶液の一塩化ヨウ素が、フェノール１モルに対して０．５モル未満であると、未反応のフェノールが発生するため、この未反応のフェノールを除去する必要があるだけでなく、反応に寄与しないフェノールの分だけ原料コストが上昇してしまう。一方、一塩化ヨウ素水溶液の一塩化ヨウ素が、フェノール１モルに対して１．５モルを超えると、２，４−ジヨード体が多く生成されるため、この２，４−ジヨード体を除去する必要があり、作業コストが上昇してしまう。 Further, in the reaction step, if the iodine monochloride aqueous solution of iodine monochloride is less than 0.5 mol with respect to 1 mol of phenol, unreacted phenol is generated. Therefore, it is necessary to remove this unreacted phenol. In addition, the raw material cost increases by the amount of phenol that does not contribute to the reaction. On the other hand, when the amount of iodine monochloride in the aqueous solution of iodine monochloride exceeds 1.5 mol with respect to 1 mol of phenol, a large amount of 2,4-diiodine is produced. Therefore, it is necessary to remove this 2,4-diiodine. This increases work costs.
したがって、反応工程にて用いられる一塩化ヨウ素水溶液の一塩化ヨウ素は、フェノール１モルに対して０．５モル以上１．５モル以下であると好ましい。 Therefore, iodine monochloride used in the reaction step is preferably 0.5 mol or more and 1.5 mol or less with respect to 1 mol of phenol.
また、反応工程では、反応溶媒として水と混和しない有機溶媒を用いることが好ましい。 In the reaction step, an organic solvent that is not miscible with water is preferably used as the reaction solvent.
有機溶媒は、水との相互溶解性が低く、生成物のｐ−ヨードフェノールの溶解性が低く、ｏ−ヨードフェノールの溶解性が高い溶媒であればよいが、炭素数６〜１０の脂肪族炭化水素、炭素数４〜６の脂肪族酢酸エステル類、炭素数４〜８の脂肪族エーテル類のいずれかが好ましく、特にｎ−ヘキサンが好ましい。 The organic solvent may be any solvent that has low mutual solubility with water, low solubility of the product p-iodophenol, and high solubility of o-iodophenol. Any of hydrocarbons, aliphatic acetates having 4 to 6 carbon atoms, and aliphatic ethers having 4 to 8 carbon atoms is preferable, and n-hexane is particularly preferable.
反応工程にてフェノールと一塩化ヨウ素水溶液とを反応させる際には、通常、反応温度が３０℃以上７０℃以下が適当であるが、４０℃以上６０℃以下であると、温度制御および反応速度調整に適した温度であるので好ましい。 When reacting phenol and iodine monochloride aqueous solution in the reaction step, the reaction temperature is usually 30 ° C. or higher and 70 ° C. or lower, but if it is 40 ° C. or higher and 60 ° C. or lower, temperature control and reaction rate This is preferable because the temperature is suitable for adjustment.
ここで、ｐ−ヨードフェノールを製造する際には、反応工程後に、この反応工程で得られた反応液を反応温度以下、例えば室温である約２０℃まで冷却してｐ−ヨードフェノールを析出させる結晶化工程にてｐ−ヨードフェノールを単離することが好ましい。 Here, when producing p-iodophenol, after the reaction step, the reaction solution obtained in this reaction step is cooled to a reaction temperature or lower, for example, about 20 ° C., which is room temperature, to deposit p-iodophenol. It is preferable to isolate p-iodophenol in the crystallization step.
また、この場合、反応工程から結晶化工程までを同一反応容器で行うことがより好ましい。 In this case, it is more preferable to carry out the reaction step to the crystallization step in the same reaction vessel.
そして、結晶化工程後、析出したｐ−ヨードフェノールを例えば濾過などの固液分離方法により回収する。 Then, after the crystallization step, the precipitated p-iodophenol is recovered by a solid-liquid separation method such as filtration.
上述のｐ−ヨードフェノールの製造方法によれば、フェノールと一塩化ヨウ素水溶液とを反応させるため、反応工程では[化２]に示すように反応が進行し、投入した一塩化ヨウ素のヨウ素が全て反応に寄与する。 According to the above-mentioned method for producing p-iodophenol, since the phenol and the aqueous solution of iodine monochloride are reacted, the reaction proceeds as shown in [Chemical Formula 2] in the reaction step, and all of the iodine of iodine monochloride added is all Contributes to the reaction.
したがって、ヨウ素を効率的に無駄なく反応させることが可能になり、効率的にｐ−ヨードフェノールを製造できる。 Therefore, it becomes possible to react iodine efficiently without waste, and p-iodophenol can be produced efficiently.
また、反応工程では、[化２]にて示すように、副生成物として塩化水素（ＨＣｌ）が生成される。塩化水素は、通常の有機溶媒には溶解しないため、塩化水素ガスとなって放散されるが、反応工程にて一塩化ヨウ素水溶液を用いることにより、副生成物の塩化水素が水に溶解して塩酸となって、塩化水素ガスが放散されないので、塩化水素ガスの除去設備などが必要なく、工業化をする際に経済的である。 In the reaction step, hydrogen chloride (HCl) is generated as a by-product as shown in [Chemical Formula 2]. Since hydrogen chloride does not dissolve in ordinary organic solvents, it is dissipated as hydrogen chloride gas. By using iodine monochloride aqueous solution in the reaction process, by-product hydrogen chloride dissolves in water. Since it becomes hydrochloric acid and hydrogen chloride gas is not diffused, there is no need for equipment for removing hydrogen chloride gas, which is economical for industrialization.
また、このように反応工程にて一塩化ヨウ素水溶液を用いて副生成物を塩酸とすることにより、ｐ−ヨードフェノールの固液分離後の濾液から有機溶媒と塩酸と分液操作するだけで有機溶媒および塩酸を回収できるので、環境負荷を軽減できる。 In addition, by using the aqueous solution of iodine monochloride in the reaction step as hydrochloric acid as a by-product in this manner, the organic solvent and hydrochloric acid can be separated from the filtrate after the solid-liquid separation of p-iodophenol by simply performing a liquid separation operation. Since the solvent and hydrochloric acid can be recovered, the environmental burden can be reduced.
フェノール１モルに対して一塩化ヨウ素水溶液の一塩化ヨウ素を０．５モル以上１．５モル以下にすることにより、例えば、未反応のフェノールの発生を抑制できるとともに、ｏ−ヨードフェノールや２，４−ジヨードフェノールの生成などの目的物以外の副生成物の生成を抑制できるので、効率的にｐ−ヨードフェノールを製造できる。 By making the iodine monochloride aqueous solution of iodine monochloride in an amount of 0.5 mol to 1.5 mol with respect to 1 mol of phenol, for example, generation of unreacted phenol can be suppressed, and o-iodophenol, 2, Since production of by-products other than the target product such as production of 4-diiodophenol can be suppressed, p-iodophenol can be efficiently produced.
フェノールと一塩化ヨウ素水溶液とを反応させる際に、反応溶媒として有機溶媒を用いることにより、有機溶媒に例えば、ｏ−ヨードフェノールや２，４−ジヨードフェノールの生成などの目的物以外の副生成物を選択的に抽出できるので、効率的にｐ−ヨードフェノールを製造できる。 When reacting phenol with iodine monochloride aqueous solution, by using an organic solvent as a reaction solvent, for example, by-products other than the target product such as o-iodophenol and 2,4-diiodophenol are produced in the organic solvent. Since a product can be selectively extracted, p-iodophenol can be produced efficiently.
また、有機溶媒として、炭素数６〜１０の脂肪族炭化水素、炭素数４〜６の脂肪族酢酸エステル類、炭素数４〜８の脂肪族エーテル類のいずれかを用いることにより、より正確に目的物以外の副生成物を選択的に抽出できるので、効率的にｐ−ヨードフェノールを製造できる。 In addition, as an organic solvent, by using any of aliphatic hydrocarbons having 6 to 10 carbon atoms, aliphatic acetates having 4 to 6 carbon atoms, and aliphatic ethers having 4 to 8 carbon atoms, it is possible to more accurately. Since a by-product other than the target product can be selectively extracted, p-iodophenol can be produced efficiently.
反応工程後、結晶化工程にて、反応液を反応温度以下まで冷却してｐ−ヨードフェノールを析出させるとともに、反応工程から結晶化工程までを同一反応容器にて行うことにより、例えば上述の特許文献１や特許文献２のようにクロロホルムやトルエンでｐ−ヨードフェノールを抽出するなどのｐ−ヨードフェノールを分離する特別な工程を必要とせず、容易にｐ−ヨードフェノールを製造できる。 After the reaction step, in the crystallization step, the reaction solution is cooled to below the reaction temperature to precipitate p-iodophenol, and the reaction step to the crystallization step are performed in the same reaction vessel, for example, the above-mentioned patent The p-iodophenol can be easily produced without requiring a special step of separating the p-iodophenol such as extraction of the p-iodophenol with chloroform or toluene as in Reference 1 or Patent Document 2.
以下、本実施例および比較例について説明する。なお、以下（％）は質量基準である。 Hereinafter, this example and a comparative example will be described. In the following, (%) is based on mass.
［実施例１］
室温雰囲気下にて、冷却管および温度計を付した１００ｍｌのフラスコに反応溶媒としてのｎ−ヘキサンを２６ｍｌ投入し、攪拌下でフェノールを３．３ｇ（３５ｍｍｏｌ）加えて懸濁液とした。
[Example 1]
Under a room temperature atmosphere, 26 ml of n-hexane as a reaction solvent was charged into a 100 ml flask equipped with a condenser and a thermometer, and 3.3 g (35 mmol) of phenol was added with stirring to form a suspension.
この懸濁液を湯浴で５０℃まで昇温し、フェノールを溶解させたものに、２０％一塩化ヨウ素水溶液２８．４ｇ（３５ｍｍｏｌ）を３０分掛けて滴下した。また、滴下終了後、５０℃〜５５℃で１時間継続して攪拌し、フェノールと一塩化ヨウ素水溶液とを反応させた。 This suspension was heated to 50 ° C. in a hot water bath, and 28.4 g (35 mmol) of a 20% aqueous solution of iodine monochloride was added dropwise to the solution in which phenol was dissolved over 30 minutes. Moreover, after completion | finish of dripping, it stirred continuously at 50 to 55 degreeC for 1 hour, and made phenol and iodine monochloride aqueous solution react.
反応混合物に１０％チオ硫酸ナトリウム水溶液を加え、過剰のヨウ素を還元した後、攪拌下で反応液を２０℃まで冷却した。また、冷却により析出した結晶を濾別、洗浄および乾燥させて白色結晶５．７ｇを得た。 A 10% aqueous sodium thiosulfate solution was added to the reaction mixture to reduce excess iodine, and then the reaction solution was cooled to 20 ° C. with stirring. Further, the crystals precipitated by cooling were separated by filtration, washed and dried to obtain 5.7 g of white crystals.
白色結晶を液体クロマトログラフィで分析し定量した結果、パラ体／オルト体比は、９９．７／０．３であり、２，４−ジヨード体は０．１％未満であった。なお、フェノールの転化率は９８％であった。 As a result of analyzing and quantifying the white crystal by liquid chromatography, the para / ortho ratio was 99.7 / 0.3, and the 2,4-diiodine was less than 0.1%. The conversion rate of phenol was 98%.
［実施例２］
室温雰囲気下にて、冷却管および温度計を付した２００ｍｌのフラスコに反応溶媒としてのｎ−ヘキサンを３０ｍｌ投入し、攪拌下でフェノールを７．５ｇ（８０ｍｍｏｌ）加えて懸濁液とした。
[Example 2]
Under a room temperature atmosphere, 30 ml of n-hexane as a reaction solvent was charged into a 200 ml flask equipped with a condenser and a thermometer, and 7.5 g (80 mmol) of phenol was added under stirring to form a suspension.
この懸濁液を湯浴で６０℃まで昇温し、フェノールを溶解させたものに、３０％一塩化ヨウ素水溶液４３．３ｇ（８０ｍｍｏｌ）を３０分掛けて滴下した。また、滴下終了後、６０℃〜６５℃で１時間継続して攪拌し、フェノールと一塩化ヨウ素水溶液とを反応させた。 This suspension was heated to 60 ° C. in a hot water bath, and 43.3 g (80 mmol) of 30% iodine monochloride aqueous solution was added dropwise to the solution in which phenol was dissolved over 30 minutes. Moreover, after completion | finish of dripping, it stirred continuously at 60 to 65 degreeC for 1 hour, and made phenol and iodine monochloride aqueous solution react.
反応混合物に１０％チオ硫酸ナトリウム水溶液を加え、過剰のヨウ素を還元した後、攪拌下で反応液を２０℃まで冷却した。また、冷却により析出した結晶を濾別、洗浄および乾燥させて白色結晶１９．０ｇを得た。 A 10% aqueous sodium thiosulfate solution was added to the reaction mixture to reduce excess iodine, and then the reaction solution was cooled to 20 ° C. with stirring. Further, the crystals precipitated by cooling were separated by filtration, washed and dried to obtain 19.0 g of white crystals.
白色結晶を液体クロマトログラフィで分析し定量した結果、パラ体／オルト体比は、９９．９／０．１であり、２，４−ジヨード体は０．１％未満であった。なお、フェノールの転化率は９７％であった。 As a result of analyzing and quantifying the white crystal by liquid chromatography, the para / ortho ratio was 99.9 / 0.1, and the 2,4-diiodine was less than 0.1%. The phenol conversion was 97%.
［実施例３］
室温雰囲気下にて、冷却管および温度計を付した２００ｍｌのフラスコに反応溶媒としてのｎ−ヘキサンを１５ｍｌ投入し、攪拌下でフェノールを７．５ｇ（８０ｍｍｏｌ）加えて懸濁液とした。
[Example 3]
Under a room temperature atmosphere, 15 ml of n-hexane as a reaction solvent was charged into a 200 ml flask equipped with a condenser and a thermometer, and 7.5 g (80 mmol) of phenol was added under stirring to form a suspension.
この懸濁液を湯浴で６０℃まで昇温し、フェノールを溶解させたものに、３０％一塩化ヨウ素水溶液２１．２ｇ（４０ｍｍｏｌ）を３０分掛けて滴下した。また、滴下終了後、６０℃〜６５℃で１時間継続して攪拌し、フェノールと一塩化ヨウ素水溶液とを反応させた。 This suspension was heated to 60 ° C. in a hot water bath, and 21.2 g (40 mmol) of 30% iodine monochloride aqueous solution was added dropwise to the solution in which phenol was dissolved over 30 minutes. Moreover, after completion | finish of dripping, it stirred continuously at 60 to 65 degreeC for 1 hour, and made phenol and iodine monochloride aqueous solution react.
反応混合物に１０％チオ硫酸ナトリウム水溶液を加え、過剰のヨウ素を還元した後、攪拌下で反応液を２０℃まで冷却した。また、冷却により析出した結晶を濾別、洗浄および乾燥させて白色結晶９．０ｇを得た。 A 10% aqueous sodium thiosulfate solution was added to the reaction mixture to reduce excess iodine, and then the reaction solution was cooled to 20 ° C. with stirring. Further, the crystals precipitated by cooling were filtered off, washed and dried to obtain 9.0 g of white crystals.
白色結晶を液体クロマトログラフィで分析し定量した結果、パラ体／オルト体比は、９９．９／０．１であり、２，４−ジヨード体は０．１％未満であった。なお、フェノールの転化率は４９％であった。 As a result of analyzing and quantifying the white crystal by liquid chromatography, the para / ortho ratio was 99.9 / 0.1, and the 2,4-diiodine was less than 0.1%. The conversion rate of phenol was 49%.
［実施例４］
室温雰囲気下にて、冷却管および温度計を付した１００ｍｌのフラスコに反応溶媒としてのｎ−ヘキサンを４０ｍｌ投入し、攪拌下でフェノールを３．３ｇ（３５ｍｍｏｌ）加えて懸濁液とした。
[Example 4]
Under a room temperature atmosphere, 40 ml of n-hexane as a reaction solvent was charged into a 100 ml flask equipped with a condenser and a thermometer, and 3.3 g (35 mmol) of phenol was added with stirring to form a suspension.
この懸濁液を湯浴で５０℃まで昇温し、フェノールを溶解させたものに、２０％一塩化ヨウ素水溶液４２．６ｇ（５２．５ｍｍｏｌ）を４５分掛けて滴下した。また、滴下終了後、５０℃〜５５℃で１時間継続して攪拌し、フェノールと一塩化ヨウ素水溶液とを反応させた。 This suspension was heated to 50 ° C. in a hot water bath, and 42.6 g (52.5 mmol) of 20% iodine monochloride aqueous solution was added dropwise over 45 minutes to the solution in which phenol was dissolved. Moreover, after completion | finish of dripping, it stirred continuously at 50 to 55 degreeC for 1 hour, and made phenol and iodine monochloride aqueous solution react.
反応混合物に１０％チオ硫酸ナトリウム水溶液を加え、過剰のヨウ素を還元した後、攪拌下で反応液を２０℃まで冷却した。また、冷却により析出した結晶を濾別、洗浄および乾燥させて白色結晶５．０ｇを得た。 A 10% aqueous sodium thiosulfate solution was added to the reaction mixture to reduce excess iodine, and then the reaction solution was cooled to 20 ° C. with stirring. In addition, crystals precipitated by cooling were filtered, washed and dried to obtain 5.0 g of white crystals.
白色結晶を液体クロマトログラフィで分析し定量した結果、パラ体／オルト体比は、９７．２／２．８であり、２，４−ジヨード体は１．０％未満であった。なお、フェノールの転化率は１００％であった。 As a result of analyzing and quantifying the white crystal by liquid chromatography, the para / ortho ratio was 97.2 / 2.8, and the 2,4-diiodide was less than 1.0%. The phenol conversion was 100%.
［実施例５］
室温雰囲気下にて、冷却管および温度計を付した２００ｍｌのフラスコに反応溶媒としてのｎ−ヘキサンを１５ｍｌ投入し、攪拌下でフェノールを７．５ｇ（８０ｍｍｏｌ）加えて懸濁液とした。
[Example 5]
Under a room temperature atmosphere, 15 ml of n-hexane as a reaction solvent was charged into a 200 ml flask equipped with a condenser and a thermometer, and 7.5 g (80 mmol) of phenol was added under stirring to form a suspension.
この懸濁液を湯浴で６０℃まで昇温し、フェノールを溶解させたものに、３０％一塩化ヨウ素水溶液２１．２ｇ（４０ｍｍｏｌ）を３０分掛けて滴下した。また、滴下終了後、６０℃〜６５℃で１時間継続して攪拌し、フェノールと一塩化ヨウ素水溶液とを反応させた。 This suspension was heated to 60 ° C. in a hot water bath, and 21.2 g (40 mmol) of 30% iodine monochloride aqueous solution was added dropwise to the solution in which phenol was dissolved over 30 minutes. Moreover, after completion | finish of dripping, it stirred continuously at 60 to 65 degreeC for 1 hour, and made phenol and iodine monochloride aqueous solution react.
反応混合物に１０％チオ硫酸ナトリウム水溶液を加え、過剰のヨウ素を還元した後、攪拌下で反応液を２０℃まで冷却した。また、冷却により析出した結晶を濾別、洗浄および乾燥させて白色結晶９．０ｇを得た。 A 10% aqueous sodium thiosulfate solution was added to the reaction mixture to reduce excess iodine, and then the reaction solution was cooled to 20 ° C. with stirring. Further, the crystals precipitated by cooling were filtered off, washed and dried to obtain 9.0 g of white crystals.
白色結晶を液体クロマトログラフィで分析し定量した結果、パラ体／オルト体比は、９９．９／０．１であり、２，４−ジヨード体は０．１％未満であった。なお、フェノールの転化率は４９％であった。 As a result of analyzing and quantifying the white crystal by liquid chromatography, the para / ortho ratio was 99.9 / 0.1, and the 2,4-diiodine was less than 0.1%. The conversion rate of phenol was 49%.
本発明は、各種化合物の合成原料や、医薬・農薬中間体合成試薬として有用なｐ−ヨードフェノールの工業的な生産に利用することができる。 INDUSTRIAL APPLICABILITY The present invention can be used for industrial production of p-iodophenol, which is useful as a raw material for synthesis of various compounds and as a reagent for synthesizing pharmaceutical and agrochemical intermediates.
Claims (5)
ことを特徴とするｐ−ヨードフェノールの製造方法。 A method for producing p-iodophenol, comprising a reaction step of reacting phenol with an aqueous solution of iodine monochloride.
ことを特徴とする請求項１記載のｐ−ヨードフェノールの製造方法。 The method for producing p-iodophenol according to claim 1, wherein iodine monochloride in the aqueous solution of iodine monochloride is 0.5 mol to 1.5 mol with respect to 1 mol of phenol.
ことを特徴とする請求項１または２記載のｐ−ヨードフェノールの製造方法。 In the reaction step, an organic solvent immiscible with water is used as the reaction solvent. The method for producing p-iodophenol according to claim 1 or 2.
ことを特徴とする請求項３の記載のｐ−ヨードフェノールの製造方法。 The organic solvent is any of aliphatic hydrocarbons having 6 to 10 carbon atoms, aliphatic acetates having 4 to 6 carbon atoms, and aliphatic ethers having 4 to 8 carbon atoms. The manufacturing method of p-iodophenol of description.
反応工程から結晶化工程までを同一反応容器で行う
ことを特徴とする請求項１ないし４のいずれか記載のｐ−ヨードフェノールの製造方法。 After the reaction step, the reaction solution obtained in this reaction step is cooled to the reaction temperature or lower to comprise a crystallization step of depositing p-iodophenol,
The method for producing p-iodophenol according to any one of claims 1 to 4, wherein the reaction step to the crystallization step are carried out in the same reaction vessel.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4029816A (en) * | 1975-11-25 | 1977-06-14 | Merck & Co., Inc. | Substituted 2-aminomethyl-6-iodophenols |
| JP2001526677A (en) * | 1997-05-23 | 2001-12-18 | ニユコメド・イメージング・アクシエセルカペト | Production of triiodobenzene compounds |
| JP2002097160A (en) * | 2000-09-20 | 2002-04-02 | Meiji Seika Kaisha Ltd | Method of manufacturing iodized aromatic compound |
| WO2008143141A1 (en) * | 2007-05-18 | 2008-11-27 | Nippoh Chemicals Co., Ltd. | Method for producing halogenated aromatic compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4029816A (en) * | 1975-11-25 | 1977-06-14 | Merck & Co., Inc. | Substituted 2-aminomethyl-6-iodophenols |
| JP2001526677A (en) * | 1997-05-23 | 2001-12-18 | ニユコメド・イメージング・アクシエセルカペト | Production of triiodobenzene compounds |
| JP2002097160A (en) * | 2000-09-20 | 2002-04-02 | Meiji Seika Kaisha Ltd | Method of manufacturing iodized aromatic compound |
| WO2008143141A1 (en) * | 2007-05-18 | 2008-11-27 | Nippoh Chemicals Co., Ltd. | Method for producing halogenated aromatic compound |
Non-Patent Citations (1)
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| JPN6014051069; Ｂｕｌｌ． Ｃｈｅｍ． Ｓｏｃ． Ｊｐｎ． Ｖｏｌ．７５， Ｎｏ．２, 2002, ｐ．３３９-３４５ * |
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