JP3626542B2 - Method for producing thiophenes - Google Patents

Description

【０００７】
（式中、Ｒ^１ は水素原子、アルキル基、シクロアルキル基またはアリール基を表し、Ｒ^２ は保護されたホルミル基を表す。）
で示される１，４−ジアルデヒド誘導体（以下、これを１，４−ジアルデヒド誘導体（Ｉ）と略記することがある）を添加することを特徴とする下記一般式（ＩＩ）
【０００８】
【化４】

【０００９】
（式中、Ｒ^１ は前記定義のとおりである。）
で示されるチオフェン類（以下、これをチオフェン類（ＩＩ）と略記することがある）の製造法を提供することにより達成される。
【００１０】
【発明の実施の形態】
上記一般式（Ｉ）および（ＩＩ）において、Ｒ^１ が表すアルキル基は、直鎖状、分岐鎖状のいずれでもよく、例えばメチル基、エチル基、プロピル基、イソプロピル基、ブチル基、第二級ブチル基、ペンチル基、ヘキシル基等が挙げられる。シクロアルキル基としては、シクロプロピル基、シクロペンチル基等が挙げられる。かかるアルキル基およびシクロアルキル基は塩素原子、臭素原子、ヨウ素原子等のハロゲン原子；メトキシ基、エトキシ基、プロポキシ基、イソプロポキシ基等のアルコキシ基；メトキシカルボニル基、エトキシカルボニル基、プロポキシカルボニル基等のアルコキシカルボニル基；フェニル基、メチルフェニル基、メトキシフェニル基、クロロフェニル基等のアリール基等で置換されていてもよい。
【００１１】
Ｒ^１ が表すアリール基としては、例えばフェニル基、ナフチル基等が挙げられ、これらは上記のアルキル基と同様にハロゲン原子、アルコキシ基、アルコキシカルボニル基等で置換されていてもよい。
【００１２】
また、Ｒ^２ が表す保護されたホルミル基としては、例えばジアルコキシメチル基、置換基を有していてもよいエチレンジオキシメチル基、置換基を有していてもよいプロパンジオキシメチル基等が挙げられ、具体的には下記に示すものを挙げることができる。
【００１３】
【化５】

【００１４】
次に、本発明の反応を詳細に説明する。
反応は、通常、常圧下または加圧下で行う。
【００１５】
反応に使用する塩化水素は、適当な溶媒に溶解しておく。用いられる溶媒としては、反応を著しく阻害せずチオフェン類（ＩＩ）と分離可能なものであれば特に制限されないが、例えば、ヘキサン、オクタン、デカリン、ベンゼン、トルエン、キシレン、クメン、メシチレン、シメン、テトラリン、クロロベンゼン、ジクロロベンゼン、ブロモベンゼン、ニトロベンゼン等の炭化水素系溶媒；ジイソプロピルエーテル、テトラヒドロフラン、ジオキサン、ジグライム、トリグライム、テトラグライム等のエーテル系溶媒；メタノール、エタノール、プロパノール、イソプロパノール、ブタノール、ヘキサノール、オクタノール、エチレングリコール等のアルコール系溶媒等が挙げられる。中でもアルコール系溶媒は、塩化水素および硫化水素の溶解度が高いことから好ましい。これらの溶媒は単独で、または２種以上の組合わせで使用することもできる。溶媒の使用量は、添加する１，４−ジアルデヒド誘導体（Ｉ）に対して０．０１〜１００容量倍の範囲が好ましく、０．１から１０容量倍の範囲がより好ましい。
【００１６】
溶媒中の塩化水素濃度（Ａモル／Ｌ）は、反応温度（ｔ℃）との関係において、ｔとＡの積として１．０から５００の範囲であることが好ましい。塩化水素濃度は０．０１〜５モル／Ｌの範囲が好ましく、反応温度は、塩化水素濃度によっても変化するが、２０℃〜１８０℃の範囲が好ましい。
【００１７】
好ましい反応温度と塩化水素濃度の組み合わせは、常圧の場合、例えば、
反応温度：２０℃；塩化水素濃度：１．５〜５．０モル／Ｌ、
反応温度：４０℃；塩化水素濃度：０．５〜４．０モル／Ｌ、
反応温度：６３℃；塩化水素濃度：０．１〜３．０モル／Ｌ、
反応温度：１００℃；塩化水素濃度：０．０３〜１．０モル／Ｌ
等である。加圧下の場合、例えば、
反応温度：６３℃；塩化水素濃度：０．５〜６．０モル／Ｌ、
反応温度：８０℃；塩化水素濃度：０．１〜５．０モル／Ｌ
等である。
【００１８】
塩化水素は反応開始時に一括して仕込む方法が簡便であるが、１，４−ジアルデヒド誘導体（Ｉ）の添加中または添加終了後に、好適な塩化水素濃度を維持するように追加することもできる。
【００１９】
反応を常圧で行う場合、塩化水素を溶解した溶液中に硫化水素を流通させながら１，４−ジアルデヒド誘導体（Ｉ）を添加していく方法が好ましい。加圧下の場合、ゲージ圧で０．００１気圧から圧力容器の耐圧範囲内で行なわれ、塩化水素を溶解した溶液中に硫化水素加圧下で１，４−ジアルデヒド誘導体（Ｉ）を添加していく方法が好ましい。
【００２０】
硫化水素の供給速度は、常圧の場合、１，４−ジアルデヒド誘導体（Ｉ）の添加速度に対して０．５〜１．５モル倍が好ましい。これ以上の速度で供給しても格別な効果はない。１，４−ジアルデヒド誘導体（Ｉ）を添加終了後、吸収量に応じて硫化水素の供給速度を遅くするのが経済的に有利である。また、硫化水素の供給に際しては、硫化水素が溶液中に効率よく拡散・吸収される操作方法が好ましい。
【００２１】
１，４−ジアルデヒド誘導体（Ｉ）を添加する時間は通常１分間から１００時間、好ましくは１０分間から５０時間の範囲であるが、反応条件に応じて最適の添加時間を適宜選択することができる。添加は連続添加でも分割添加でもよい。また、１，４−ジアルデヒド誘導体（Ｉ）を添加終了後、１分間から１００時間、好ましくは１０分間から５０時間の範囲で熟成させることが好ましい。
【００２２】
反応後の単離精製は通常の方法により行うことができる。例えば、反応混合物をアルカリで中和し、水にあけ、分液または有機溶媒で抽出する。抽出液を濃縮して粗生成物を得、該粗生成物を必要に応じて蒸留、再結晶、クロマトグラフィー等により精製し、チオフェン類（ＩＩ）を得る。
【００２３】
原料となる１、４−ジアルデヒド誘導体（Ｉ）は、公知の方法により合成できる。例えば、ジャーナル・オブ・オーガニック・ケミストリー（Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ）、３８巻、２３６１頁（１９７３年）に示される方法により、容易に製造できる。
【００２４】
【実施例】
以下、実施例および比較例により本発明を具体的に説明するが、本発明はこれらの実施例により何ら限定されるものではない。
【００２５】
実施例１
撹拌機、温度計、ガス吹き込み管、滴下漏斗、冷却器を備えた５００ｍＬ容４口フラスコにメタノール１５０ｍＬを仕込み、室温で塩化水素を吹き込み、塩化水素濃度１．７モル／Ｌに調製した。次に６２〜６４℃に加温し、硫化水素を９２ｍＬ／分の割合で吹き込みを開始した。５−メチル−１，３−ジオキサン−２−プロパナール９９．２ｇ（５７７ミリモル）を３．５時間かけて滴下した（滴下終了時の反応液中の原料濃度は４０％に相当）。滴下終了後も硫化水素の吹き込みを３時間続け、熟成した。ガスクロマトグラフィーで反応液を分析したところ、収率６４％で３−メチルチオフェンが生成していた。
反応液に水酸化ナトリウム水溶液を加え、中和後、ヘキサンで抽出した。抽出液を常圧で単蒸留し、３−メチルチオフェン３５．０ｇ（３５７ミリモル）を含むヘキサン留分を得た。この留分を精密蒸留することにより、純度９９％以上の３−メチルチオフェンが得られた。
【００２６】
比較例１
ジャーナル・オブ・オーガニック・ケミストリー（Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ）、３８巻、２３６１頁（１９７３年）に記載された方法にしたがって、実施例１と同じ原料濃度で反応を行った。
５−メチル−１，３−ジオキサン−２−プロパナール１０ｇ（５８ミリモル）をメタノール１５ｍＬに溶解した。この溶液に硫化水素を室温で１時間吹き込み、飽和させた。次に６０℃に加熱し、塩化水素を継続的に２時間、反応液表面に流通させた。ガスクロマトグラフィーで反応液を分析したところ、３−メチルチオフェンが１．８ｇ（１８ミリモル）生成していた。収率は３１％であった。
【００２７】
比較例２
テトラヘドロン（Ｔｅｔｒａｈｅｄｒｏｎ ）、３２巻、２８１７頁（１９７６年）に記載された方法にしたがって、実施例１と同じ原料濃度で反応を行った。
５−メチル−１，３−ジオキサン−２−プロパナール１０ｇ（５８ミリモル）をエタノール１５ｍＬの溶液に溶解した。この溶液に、−５０℃で硫化水素を吹き込んだ。次に、塩化水素を１．５時間吹き込んだ。さらに同温度で４時間硫化水素を吹き込んだ。反応液をガスクロマトグラフィーを用いて分析した結果、３−メチルチオフェンが０．８５ｇ（８．７ミリモル）生成していた。収率は１５％であった。
【００２８】
実施例２
ガス吹き込み口、等圧ラインを備えた耐圧ガラス製滴下漏斗、圧力ゲージを備えた１００ｍＬ容３口耐圧ガラス管に、塩化水素濃度１．７モル／Ｌのメタノール１５ｍＬを仕込んだ。次に８０℃に加温し、硫化水素でゲージ圧１．０気圧に加圧した。ゲージ圧を１．０気圧に保ったまま、５−メチル−１，３−ジオキサン−２−プロパナール１０ｇ（５８ミリモル）を３時間かけて滴下した。滴下終了後も圧を保ったまま、２時間熟成した。反応液をガスクロマトグラフィーを用いて分析した結果、３−メチルチオフェンが４．２ｇ（４３ミリモル）生成していた（収率７４％）。
【００２９】
実施例３
実施例２において、メタノール１５ｍＬの代わりにオクタノール１５ｍＬを用いる以外は実施例２と同様にして反応を行い、反応液をガスクロマトグラフィーを用いて分析した結果、３−メチルチオフェンが３．８ｇ（３９ミリモル）生成していた（収率６７％）。
【００３０】
実施例４
実施例２において、メタノール１５ｍＬの代わりにエチレングリコール１５ｍＬを用いる以外は実施例２と同様にして反応を行い、反応液をガスクロマトグラフィーを用いて分析した結果、３−メチルチオフェンが３．４ｇ（３５ミリモル）生成していた（収率６０％）。
【００３１】
実施例５
実施例２において、５−メチル−１，３−ジオキサン−２−プロパナール１０ｇ（５８ミリモル）の代わりに１，３−ジオキサン−２−プロパナール９．２ｇ（５８ミリモル）を用いる以外は実施例２と同様にして反応を行い、反応液をガスクロマトグラフィーを用いて分析した結果、チオフェンが３．４ｇ（４０ミリモル）生成していた（収率６９％）。
【００３２】
実施例６
実施例２において、５−メチル−１，３−ジオキサン−２−プロパナール１０ｇ（５８ミリモル）の代わりに５−イソプロピル−１，３−ジオキサン−２−プロパナール１１．６ｇ（５８ミリモル）を用いる以外は実施例２と同様にして反応を行い、反応液をガスクロマトグラフィーを用いて分析した結果、３−イソプロピルチオフェンが５．２ｇ（４１ミリモル）生成していた（収率７１％）。
【００３３】
実施例７
実施例２において、５−メチル−１，３−ジオキサン−２−プロパナール１０ｇ（５８ミリモル）の代わりに５−フェニル−１，３−ジオキサン−２−プロパナール１３．６ｇ（５８ミリモル）を用いる以外は実施例２と同様にして反応を行い、反応液をガスクロマトグラフィーを用いて分析した結果、３−フェニルチオフェンが６．１ｇ（３８ミリモル）生成していた（収率６６％）。
【００３４】
実施例８〜９
実施例１において、５−メチル−１，３−ジオキサン−２−プロパナール９９．２ｇ（５７７ミリモル）の代わりに表１に示す化合物５７７ミリモルを用いる以外は実施例１と同様にして反応を行い、３−メチルチオフェンを得た。結果を表１に示した。
【００３５】
【表１】

【００３６】
【発明の効果】
本発明によれば、チオフェン類を温和な条件で選択性よく製造することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing thiophenes. The thiophenes produced according to the present invention are useful as synthetic intermediates for various pharmaceuticals and agricultural chemicals.
[0002]
[Prior art]
As a method for producing thiophene and derivatives thereof, (1) in a nitrogen atmosphere, isoprene or 2-methyl-2-butene and hydrogen sulfide in the presence of a composite catalyst composed of chromium oxide, aluminum oxide and potassium oxide at 400 ° C. A method of obtaining 3-methylthiophene by reacting at the above high temperature (for example, see JP-A-50-122483, JP-A-50-123661, JP-A-51-122061), (2) Isoprene A method of obtaining 3-methylthiophene by reacting butadienes such as sulfur with sulfur at a high temperature of 400 ° C. or higher (see JP-A-54-76574), (3) alcohols such as 3-methyl-1-butanol And carbon disulfide are reacted at about 500 ° C. in the presence of a catalyst comprising chromium oxide and aluminum oxide (US Patent No. 822289), (4) A method of obtaining 3-methylthiophene by circulating hydrogen chloride gas in a solution in which a 1,4-dialdehyde derivative and hydrogen sulfide are dissolved [Journal of Organic Chemistry (Journal of Organic Chemistry). ), 38, 2361 (1973)], (5) Hydrogen sulfide and hydrogen chloride are dissolved at a low temperature in a solution in which a 1,4-diketone derivative such as 1,4-diphenyl-1,4-butanedione is dissolved. A method for obtaining 2,5-disubstituted-thiophene such as 2,5-diphenylthiophene by circulation (see Tetrahedron, 32, 2817 (1976)), (6) 1,4-diphenyl- In a solution in which a 1,4-diketone derivative such as 1,4-butanedione and a dehydrating agent are mixed, And hydrogen chloride to obtain 2,5-disubstituted-thiophene such as 2,5-diphenylthiophene [Journal of Organic Chemistry, 17, 1405 (1952) Reference] is known.
[0003]
[Problems to be solved by the invention]
In the above methods (1) to (3), high temperature is required, and tar and coke are produced. Therefore, when a catalyst is used, it is necessary to frequently replace and regenerate the catalyst. There were problems such as easy formation of isomers such as thiophene. In the methods (4) and (5), since the concentration of the substrate (1,4-dialdehyde derivative or 1,4-diketone derivative) in the solution is low and the amount of hydrogen chloride to be circulated increases, This is not an industrially advantageous method. Furthermore, when the concentration of the raw material is increased in such a method, a large amount of high-molecular-weight by-products are generated as is apparent from the comparative examples described later. Therefore, it is necessary to carry out the reaction with a diluted solution, and the production efficiency is low. The method (6) is not economical because zinc chloride or tin chloride must be used in an equimolar amount or more with respect to the raw material as a dehydrating agent.
[0004]
Therefore, an object of the present invention is to provide an industrial method with high production efficiency capable of producing thiophenes at a high substrate concentration with good selectivity under mild conditions.
[0005]
[Means for Solving the Problems]
As a result of intensive studies to solve such problems, the present inventors have found that thiophenes can be produced in a high yield that cannot be achieved by conventional methods by using a method of adding a substrate to a hydrogen chloride solution. . That is, according to the present invention, the above object is achieved by adding the following general formula (I)
[0006]
[Chemical 3]

[0007]
(In the formula, R ¹ represents a hydrogen atom, an alkyl group, a cycloalkyl group or an aryl group, and R ² represents a protected formyl group.)
1,4-dialdehyde derivative (hereinafter, this may be abbreviated as 1,4-dialdehyde derivative (I)) is added.
[0008]
[Formula 4]

[0009]
(Wherein R ¹ is as defined above.)
This is achieved by providing a method for producing the thiophenes represented by the formula (hereinafter sometimes abbreviated as thiophenes (II)).
[0010]
DETAILED DESCRIPTION OF THE INVENTION
In the above general formulas (I) and (II), the alkyl group represented by R ¹ may be either linear or branched, such as methyl, ethyl, propyl, isopropyl, butyl, second Examples include a butyl group, a pentyl group, and a hexyl group. Examples of the cycloalkyl group include a cyclopropyl group and a cyclopentyl group. Such alkyl group and cycloalkyl group are halogen atoms such as chlorine atom, bromine atom and iodine atom; alkoxy groups such as methoxy group, ethoxy group, propoxy group and isopropoxy group; methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group and the like And may be substituted with an aryl group such as a phenyl group, a methylphenyl group, a methoxyphenyl group or a chlorophenyl group.
[0011]
Examples of the aryl group represented by R ¹ include a phenyl group and a naphthyl group, and these may be substituted with a halogen atom, an alkoxy group, an alkoxycarbonyl group or the like in the same manner as the above alkyl group.
[0012]
Examples of the protected formyl group represented by R ² include a dialkoxymethyl group, an ethylenedioxymethyl group which may have a substituent, and a propanedioxymethyl group which may have a substituent. Specifically, the following can be mentioned.
[0013]
[Chemical formula 5]

[0014]
Next, the reaction of the present invention will be described in detail.
The reaction is usually carried out under normal pressure or under pressure.
[0015]
Hydrogen chloride used in the reaction is dissolved in a suitable solvent. The solvent used is not particularly limited as long as it does not significantly inhibit the reaction and can be separated from the thiophenes (II). For example, hexane, octane, decalin, benzene, toluene, xylene, cumene, mesitylene, cymene, Hydrocarbon solvents such as tetralin, chlorobenzene, dichlorobenzene, bromobenzene, nitrobenzene; ether solvents such as diisopropyl ether, tetrahydrofuran, dioxane, diglyme, triglyme, tetraglyme; methanol, ethanol, propanol, isopropanol, butanol, hexanol, octanol And alcohol solvents such as ethylene glycol. Among these, alcohol solvents are preferable because of high solubility of hydrogen chloride and hydrogen sulfide. These solvents can be used alone or in combination of two or more. The amount of the solvent used is preferably in the range of 0.01 to 100 times by volume, more preferably in the range of 0.1 to 10 times by volume with respect to the 1,4-dialdehyde derivative (I) to be added.
[0016]
The hydrogen chloride concentration (A mol / L) in the solvent is preferably in the range of 1.0 to 500 as the product of t and A in relation to the reaction temperature (t ° C.). The hydrogen chloride concentration is preferably in the range of 0.01 to 5 mol / L, and the reaction temperature varies depending on the hydrogen chloride concentration, but is preferably in the range of 20 ° C to 180 ° C.
[0017]
A preferable combination of reaction temperature and hydrogen chloride concentration is, for example, at normal pressure, for example,
Reaction temperature: 20 ° C .; hydrogen chloride concentration: 1.5 to 5.0 mol / L,
Reaction temperature: 40 ° C .; hydrogen chloride concentration: 0.5 to 4.0 mol / L,
Reaction temperature: 63 ° C .; hydrogen chloride concentration: 0.1-3.0 mol / L,
Reaction temperature: 100 ° C .; hydrogen chloride concentration: 0.03 to 1.0 mol / L
Etc. For example, under pressure,
Reaction temperature: 63 ° C .; hydrogen chloride concentration: 0.5 to 6.0 mol / L,
Reaction temperature: 80 ° C .; hydrogen chloride concentration: 0.1-5.0 mol / L
Etc.
[0018]
Hydrogen chloride can be added in a simple manner at the start of the reaction, but it can also be added to maintain a suitable hydrogen chloride concentration during or after the addition of the 1,4-dialdehyde derivative (I). .
[0019]
When the reaction is carried out at normal pressure, a method of adding the 1,4-dialdehyde derivative (I) while circulating hydrogen sulfide in a solution in which hydrogen chloride is dissolved is preferable. In the case of pressurization, the pressure is within a pressure range of 0.001 atm to a pressure vessel with a gauge pressure, and 1,4-dialdehyde derivative (I) is added to the solution in which hydrogen chloride is dissolved under pressure of hydrogen sulfide. Is preferred.
[0020]
In the case of normal pressure, the supply rate of hydrogen sulfide is preferably 0.5 to 1.5 mol times the addition rate of the 1,4-dialdehyde derivative (I). Supplying at a higher speed has no particular effect. After the addition of the 1,4-dialdehyde derivative (I), it is economically advantageous to reduce the supply rate of hydrogen sulfide according to the amount of absorption. In addition, when supplying hydrogen sulfide, an operation method in which hydrogen sulfide is efficiently diffused and absorbed in the solution is preferable.
[0021]
The time for adding the 1,4-dialdehyde derivative (I) is usually in the range of 1 minute to 100 hours, preferably 10 minutes to 50 hours. The optimum addition time can be appropriately selected according to the reaction conditions. it can. The addition may be continuous addition or divided addition. Further, after completion of the addition of the 1,4-dialdehyde derivative (I), aging is preferably performed in the range of 1 minute to 100 hours, preferably 10 minutes to 50 hours.
[0022]
Isolation and purification after the reaction can be carried out by a usual method. For example, the reaction mixture is neutralized with alkali, poured into water, and extracted with a liquid separation or organic solvent. The extract is concentrated to obtain a crude product, and the crude product is purified by distillation, recrystallization, chromatography or the like as necessary to obtain thiophenes (II).
[0023]
The 1,4-dialdehyde derivative (I) as a raw material can be synthesized by a known method. For example, it can be easily manufactured by the method shown in Journal of Organic Chemistry, 38, 2361 (1973).
[0024]
【Example】
EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention concretely, this invention is not limited at all by these Examples.
[0025]
Example 1
A 500 mL 4-neck flask equipped with a stirrer, thermometer, gas blowing tube, dropping funnel, and condenser was charged with 150 mL of methanol, and hydrogen chloride was blown at room temperature to prepare a hydrogen chloride concentration of 1.7 mol / L. Next, it heated to 62-64 degreeC and blowing of hydrogen sulfide was started at the rate of 92 mL / min. 99.2 g (577 mmol) of 5-methyl-1,3-dioxane-2-propanal was added dropwise over 3.5 hours (the raw material concentration in the reaction solution at the end of the addition corresponds to 40%). After completion of the dropwise addition, hydrogen sulfide was continuously blown for 3 hours to mature. When the reaction solution was analyzed by gas chromatography, 3-methylthiophene was produced in a yield of 64%.
A sodium hydroxide aqueous solution was added to the reaction solution, neutralized, and extracted with hexane. The extract was subjected to simple distillation at normal pressure to obtain a hexane fraction containing 35.0 g (357 mmol) of 3-methylthiophene. By subjecting this fraction to precision distillation, 3-methylthiophene having a purity of 99% or more was obtained.
[0026]
Comparative Example 1
The reaction was carried out at the same raw material concentration as in Example 1 according to the method described in Journal of Organic Chemistry, 38, 2361 (1973).
10 g (58 mmol) of 5-methyl-1,3-dioxane-2-propanal was dissolved in 15 mL of methanol. Hydrogen sulfide was blown into this solution at room temperature for 1 hour to saturate. Next, the mixture was heated to 60 ° C., and hydrogen chloride was continuously passed through the reaction liquid surface for 2 hours. When the reaction solution was analyzed by gas chromatography, 1.8 g (18 mmol) of 3-methylthiophene was produced. The yield was 31%.
[0027]
Comparative Example 2
The reaction was carried out at the same raw material concentration as in Example 1 according to the method described in Tetrahedron, 32, 2817 (1976).
10 g (58 mmol) of 5-methyl-1,3-dioxane-2-propanal was dissolved in a solution of 15 mL of ethanol . Hydrogen sulfide was blown into this solution at −50 ° C. Next, hydrogen chloride was blown in for 1.5 hours. Further, hydrogen sulfide was blown in at the same temperature for 4 hours. As a result of analyzing the reaction solution using gas chromatography, 0.85 g (8.7 mmol) of 3-methylthiophene was produced. The yield was 15%.
[0028]
Example 2
15 mL of methanol having a hydrogen chloride concentration of 1.7 mol / L was charged into a 100 mL three-port pressure-resistant glass tube equipped with a gas blowing port, a pressure-resistant glass dropping funnel equipped with an isobaric line, and a pressure gauge. Next, the mixture was heated to 80 ° C. and pressurized with hydrogen sulfide to a gauge pressure of 1.0 atm. While maintaining the gauge pressure at 1.0 atm, 10 g (58 mmol) of 5-methyl-1,3-dioxane-2-propanal was added dropwise over 3 hours. The aging was continued for 2 hours while maintaining the pressure even after the dropping. As a result of analyzing the reaction solution using gas chromatography, 4.2 g (43 mmol) of 3-methylthiophene was produced (yield 74%).
[0029]
Example 3
In Example 2, the reaction was conducted in the same manner as in Example 2 except that 15 mL of octanol was used instead of 15 mL of methanol, and the reaction solution was analyzed using gas chromatography. As a result, 3.8 g (39 Mmol) (yield 67%).
[0030]
Example 4
In Example 2, the reaction was carried out in the same manner as in Example 2 except that 15 mL of ethylene glycol was used instead of 15 mL of methanol, and the reaction solution was analyzed using gas chromatography. As a result, 3.4 g of 3-methylthiophene ( 35 mmol) (yield 60%).
[0031]
Example 5
In Example 2, 9.2 g (58 mmol) of 1,3-dioxane-2-propanal was used instead of 10 g (58 mmol) of 5-methyl-1,3-dioxane-2-propanal. The reaction was conducted in the same manner as in Example 2, and the reaction solution was analyzed using gas chromatography. As a result, 3.4 g (40 mmol) of thiophene was produced (yield 69%).
[0032]
Example 6
In Example 2, 11.6 g (58 mmol) of 5-isopropyl-1,3-dioxane-2-propanal is used instead of 10 g (58 mmol) of 5-methyl-1,3-dioxane-2-propanal. The reaction was conducted in the same manner as in Example 2 and the reaction solution was analyzed using gas chromatography. As a result, 5.2 g (41 mmol) of 3-isopropylthiophene was produced (yield 71%).
[0033]
Example 7
In Example 2, 13.6 g (58 mmol) of 5-phenyl-1,3-dioxane-2-propanal is used instead of 10 g (58 mmol) of 5-methyl-1,3-dioxane-2-propanal. The reaction was conducted in the same manner as in Example 2 and the reaction solution was analyzed using gas chromatography. As a result, 6.1 g (38 mmol) of 3-phenylthiophene was produced (yield 66%).
[0034]
Examples 8-9
In Example 1, the reaction was conducted in the same manner as in Example 1 except that 577 mmol of the compound shown in Table 1 was used instead of 99.2 g (577 mmol) of 5-methyl-1,3-dioxane-2-propanal. 3-methylthiophene was obtained. The results are shown in Table 1.
[0035]
[Table 1]

[0036]
【The invention's effect】
According to the present invention, thiophenes can be produced with good selectivity under mild conditions.

Claims (2)

In the presence of hydrogen sulfide, the following general formula (I)

(In the formula, R ¹ represents a hydrogen atom, an alkyl group, a cycloalkyl group or an aryl group, and R ² represents a protected formyl group.)
1,4-dialdehyde derivative represented by the following general formula (II)

(Wherein R ¹ is as defined above.)
The manufacturing method of thiophene shown by this. The thiophene according to claim 1, wherein the product of t and A is in the range of 1.0 to 500 when the hydrogen chloride concentration in the hydrogen chloride solution is A mol / L and the reaction temperature is t ° C. Manufacturing method.