JP2004175705A - Method for producing tetrahydropyran-4-ol - Google Patents
Method for producing tetrahydropyran-4-ol Download PDFInfo
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- JP2004175705A JP2004175705A JP2002342335A JP2002342335A JP2004175705A JP 2004175705 A JP2004175705 A JP 2004175705A JP 2002342335 A JP2002342335 A JP 2002342335A JP 2002342335 A JP2002342335 A JP 2002342335A JP 2004175705 A JP2004175705 A JP 2004175705A
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- tetrahydropyran
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Abstract
Description
【0001】
【発明の属する技術分野】
本発明は、テトラヒドロピラン−4−オールの製法に関する。テトラヒドロピラン−4−オールは、医薬・農薬等の合成原料として有用な化合物である。
【0002】
【従来の技術】
従来、テトラヒドロピラン−4−オールを製造する方法としては、硫酸の存在下、3−ブテン−1−オールとホルマリンを反応させて(この時の反応液中の水分含量は、反応液に対して27.6質量%である)、収率61%(3−ブテン−1−オール基準)でテトラヒドロピラン−4−オールを製造する方法が知られている(非特許文献1参照)。しかしながら、この方法では、目的物であるテトラヒドロピラン−4−オールの収率が低いという問題があり、工業的製法としては満足するものではなかった。
【0003】
【非特許文献1】
Chem.Ber.,88,1053(1955)(第1054〜1055頁、実験項)
【0004】
【発明が解決しようとする課題】
本発明の課題は、即ち、高収率でテトラヒドロピラン−4−オールを製造出来る、工業的に有利なテトラヒドロピラン−4−オールの製法を提供するものである。
【0005】
【課題を解決するための手段】
本発明の課題は、硫酸の存在下、3−ブテン−1−オールとホルムアルデヒド誘導体とを反応させてテトラヒドロピラン−4−オールを製造する方法において、反応液中の水分含量を、反応液に対して35〜75質量%とすることを特徴とする、テトラヒドロピラン−4−オールの製法によって解決される。
【0006】
【発明の実施の形態】
本発明の反応において使用する硫酸の量は、3−ブテン−1−オール1molに対して、好ましくは0.1〜5mol、更に好ましくは0.2〜3molである。なお、硫酸の濃度は特に制限されない。
【0007】
本発明の反応において使用するホルムアルデヒド誘導体としては、例えば、ホルムアルデヒドの水溶液又はホルムアルデヒドの重合体が挙げられるが、具体的には、ホルマリン、パラホルムアルデヒド、トリオキサンが好適に使用される。なお、これらのホルムアルデヒド誘導体は、単独又は二種以上を混合して使用しても良い。
【0008】
前記ホルムアルデヒドの使用量は、3−ブテン−1−オール1molに対して、ホルムアルデヒド換算として、好ましくは0.1〜10mol、更に好ましくは0.8〜3mol、特に好ましくは1.0〜1.5molである。
【0009】
本発明の反応では、目的物であるテトラヒドロピラン−4−オールの収率を向上させるために、反応液中の水分含量を、反応液に対して35〜75質量%、好ましくは50〜70質量%に調整して反応を行う。
【0010】
本発明の反応では、水以外の溶媒を存在させても良く、その溶媒としては、反応を阻害しないものならば特に限定されず、ギ酸、酢酸等の有機酸類;メタノール、エタノール、イソプロピルアルコール、t−ブチルアルコール等のアルコール類が挙げられる。なお、これら溶媒は、単独又は二種以上を混合して使用しても良い。
【0011】
前記溶媒の使用量は、溶液の均一性や攪拌生により適宜調節するが、反応液中の水分量が、反応液に対して35〜75質量%になる範囲である。
【0012】
本発明の反応は、例えば、不活性ガスの雰囲気下、3−ブテン−1−オール、ホルムアルデヒド誘導体及び硫酸を混合した後、反応液中の水分含量を、反応液に対して35〜75質量%に調整し、攪拌しながら反応させる等の方法によって行われる。その際の反応温度は、好ましくは20〜120℃、更に好ましくは60〜100℃であり、反応圧力は特に制限されない。
【0013】
なお、最終生成物であるテトラヒドロピラン−4−オールは、反応終了後、濾過、中和、抽出、濃縮、蒸留、カラムクロマトグラフィー等による一般的な方法によって単離・精製される。
【0014】
【実施例】
次に、実施例を挙げて本発明を具体的に説明するが、本発明の範囲はこれらに限定されるものではない。
【0015】
実施例1(テトラヒドロピラン−4−オールの合成)
攪拌装置、温度計、還流冷却器及び滴下漏斗を備えた内容積100mlのガラス製フラスコに、3−ブテン−1−オール3.60g(50mmol)及び35質量%ホルマリン水溶液4.30g(50mmol)を加え、窒素雰囲気下、攪拌しながら20質量%硫酸9.00g(18.4mmol)をゆるやかに滴下し、80℃で4時間反応させた(この時の反応液中の水分含量は、反応液に対して63.0質量%である。)。反応終了後、反応液をガスクロマトグラフィーにより分析(内部標準法)したところ、テトラヒドロピラン−4−オールが4.24g生成していた(3−ブテン−1−オール基準の反応収率:83.2%)。
次いで、前記反応液をトルエン10gで2回洗浄し、48質量%水酸化ナトリウム水溶液0.77g(9.6mmol)を加えてpHを1.4〜1.5に調節した後、水5mlを加え、2−ブチルアルコール10gで2回抽出した。得られた2−ブチルアルコール層に48質量%水酸化ナトリウム水溶液0.39g(4.8mmol)を加えてpHを8〜9に調節した後、塩化ナトリウム1.1gを加えて室温で30分間攪拌した。その後、有機層と水層を分離し、水層を2−ブチルアルコール10gで抽出した。この2−ブチルアルコール抽出液と先の有機層と合わせて減圧下で濃縮し、微黄色透明液体として、純度95%(ガスクロマトグラフィーによる面積百分率)のテトラヒドロピラン−4−オール4.13gを得た(3−ブテン−1−オール基準の単離収率:77.0%)。
【0016】
実施例2〜6及び比較例1〜2
実施例1において、反応液中の水分含量を変えたこと以外は、実施例1と同様に反応を行った。その結果を表1に示す。
【0017】
【表1】
【0018】
【発明の効果】
本発明により、高収率でテトラヒドロピラン−4−オールを製造出来る、工業的に有利なテトラヒドロピラン−4−オールの製法を提供することが出来る。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing tetrahydropyran-4-ol. Tetrahydropyran-4-ol is a compound useful as a raw material for synthesis of medicines, agricultural chemicals and the like.
[0002]
[Prior art]
Conventionally, as a method for producing tetrahydropyran-4-ol, 3-buten-1-ol is reacted with formalin in the presence of sulfuric acid (at this time, the water content in the reaction solution is A method for producing tetrahydropyran-4-ol with a yield of 27.6% by mass) and a yield of 61% (based on 3-buten-1-ol) is known (see Non-Patent Document 1). However, this method has a problem that the yield of the target substance, tetrahydropyran-4-ol, is low, and has not been satisfactory as an industrial production method.
[0003]
[Non-patent document 1]
Chem. Ber. , 88 , 1053 (1955) (pp. 1054-1055, experimental section).
[0004]
[Problems to be solved by the invention]
An object of the present invention is to provide an industrially advantageous method for producing tetrahydropyran-4-ol, which can produce tetrahydropyran-4-ol in high yield.
[0005]
[Means for Solving the Problems]
An object of the present invention is to provide a method for producing tetrahydropyran-4-ol by reacting 3-buten-1-ol with a formaldehyde derivative in the presence of sulfuric acid, wherein the water content of the reaction solution is adjusted to the reaction solution. 35-75% by mass, and is solved by a method for producing tetrahydropyran-4-ol.
[0006]
BEST MODE FOR CARRYING OUT THE INVENTION
The amount of sulfuric acid used in the reaction of the present invention is preferably 0.1 to 5 mol, more preferably 0.2 to 3 mol, per 1 mol of 3-buten-1-ol. The concentration of sulfuric acid is not particularly limited.
[0007]
The formaldehyde derivative used in the reaction of the present invention includes, for example, an aqueous solution of formaldehyde or a polymer of formaldehyde. Specifically, formalin, paraformaldehyde, and trioxane are preferably used. These formaldehyde derivatives may be used alone or in combination of two or more.
[0008]
The amount of the formaldehyde to be used is preferably 0.1 to 10 mol, more preferably 0.8 to 3 mol, particularly preferably 1.0 to 1.5 mol, as 1 mol of 3-buten-1-ol, in terms of formaldehyde. It is.
[0009]
In the reaction of the present invention, in order to improve the yield of the target product, tetrahydropyran-4-ol, the water content in the reaction solution is 35 to 75% by mass, preferably 50 to 70% by mass with respect to the reaction solution. Perform the reaction by adjusting to%.
[0010]
In the reaction of the present invention, a solvent other than water may be present, and the solvent is not particularly limited as long as it does not inhibit the reaction, and organic acids such as formic acid and acetic acid; methanol, ethanol, isopropyl alcohol, t Alcohols such as -butyl alcohol. In addition, you may use these solvents individually or in mixture of 2 or more types.
[0011]
The amount of the solvent to be used is appropriately adjusted depending on the uniformity of the solution and the agitation.
[0012]
In the reaction of the present invention, for example, after mixing 3-buten-1-ol, a formaldehyde derivative and sulfuric acid under an inert gas atmosphere, the water content of the reaction solution is adjusted to 35 to 75% by mass based on the reaction solution. And the reaction is performed while stirring. The reaction temperature at that time is preferably 20 to 120 ° C, more preferably 60 to 100 ° C, and the reaction pressure is not particularly limited.
[0013]
After completion of the reaction, the final product, tetrahydropyran-4-ol, is isolated and purified by a general method such as filtration, neutralization, extraction, concentration, distillation, and column chromatography.
[0014]
【Example】
Next, the present invention will be described specifically with reference to examples, but the scope of the present invention is not limited thereto.
[0015]
Example 1 (Synthesis of tetrahydropyran-4-ol)
3.60 g (50 mmol) of 3-buten-1-ol and 4.30 g (50 mmol) of a 35 mass% aqueous solution of formalin were placed in a 100-ml glass flask equipped with a stirrer, a thermometer, a reflux condenser, and a dropping funnel. In addition, 9.00 g (18.4 mmol) of 20% by mass sulfuric acid was slowly added dropwise with stirring under a nitrogen atmosphere, and the mixture was reacted at 80 ° C. for 4 hours. 63.0% by mass.) After the completion of the reaction, the reaction solution was analyzed by gas chromatography (internal standard method). As a result, 4.24 g of tetrahydropyran-4-ol was produced (reaction yield based on 3-buten-1-ol: 83. 2%).
Next, the reaction solution was washed twice with 10 g of toluene, and after adjusting the pH to 1.4 to 1.5 by adding 0.77 g (9.6 mmol) of a 48% by mass aqueous sodium hydroxide solution, 5 ml of water was added. , And extracted twice with 10 g of 2-butyl alcohol. To the obtained 2-butyl alcohol layer, 0.39 g (4.8 mmol) of a 48% by mass aqueous sodium hydroxide solution was added to adjust the pH to 8 to 9, and then 1.1 g of sodium chloride was added, followed by stirring at room temperature for 30 minutes. did. Thereafter, the organic layer and the aqueous layer were separated, and the aqueous layer was extracted with 10 g of 2-butyl alcohol. The 2-butyl alcohol extract and the previous organic layer were combined and concentrated under reduced pressure to obtain 4.13 g of tetrahydropyran-4-ol having a purity of 95% (area percentage by gas chromatography) as a pale yellow transparent liquid. (Isolated yield based on 3-buten-1-ol: 77.0%).
[0016]
Examples 2-6 and Comparative Examples 1-2
The reaction was carried out in the same manner as in Example 1 except that the water content in the reaction solution was changed. Table 1 shows the results.
[0017]
[Table 1]
[0018]
【The invention's effect】
According to the present invention, an industrially advantageous method for producing tetrahydropyran-4-ol, which can produce tetrahydropyran-4-ol in high yield, can be provided.
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JP2002342335A JP4869537B2 (en) | 2002-11-26 | 2002-11-26 | Method for producing tetrahydropyran-4-ol |
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