JP5374085B2 - Process for producing 4-alkylresorcinol and 4-alkenylresorcinol - Google Patents
Process for producing 4-alkylresorcinol and 4-alkenylresorcinol Download PDFInfo
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本発明は、４−アルキルレゾルシノール及び４−アルケニルレゾルシノールの製造方法、特に、レゾルシノールを出発原料とし、腐食性の高い物質や、有害または有毒な物質を用いることなく、比較的低温で、工業的に有利に４−アルキルレゾルシノールおよび４−アルケニルレゾルシノールを製造可能な方法に関する。 The present invention relates to a process for producing 4-alkylresorcinol and 4-alkenylresorcinol, in particular, using resorcinol as a starting material, industrially at a relatively low temperature without using highly corrosive substances, harmful or toxic substances. Preferably, it relates to a process capable of producing 4-alkylresorcinol and 4-alkenylresorcinol.
４−アルキルレゾルシノールは医薬品や化粧品の成分あるいはその中間体として、また、樹脂の添加剤や原料として、工業的に用いられている。
例えば、４−アルキルレゾルシノールは、ニキビ原因菌に対する抗菌作用（特許文献１）、フケ原因菌に対する抗菌作用（特許文献２）、美白作用（特許文献３〜４）など、医薬品や化粧品において有用な効果を有することが知られており、４−ｎ−ブチルレゾルシノールは美白剤として既に化粧品に実用化されている。また、４−ｎ−へキシルレゾルシノールは回虫や十二指腸虫の駆虫剤として使用されている。また、４−アルケニルレゾルシノールも、美白作用を有することが知られている（特許文献５）。
4-Alkylresorcinol is industrially used as a component of pharmaceuticals and cosmetics or an intermediate thereof, and as an additive or raw material for resins.
For example, 4-alkylresorcinol is useful in pharmaceuticals and cosmetics, such as antibacterial action against acne-causing bacteria (Patent Document 1), antibacterial action against dandruff-causing bacteria (Patent Document 2), and whitening action (Patent Documents 3 to 4). 4-n-butylresorcinol has already been put into practical use in cosmetics as a whitening agent. Further, 4-n-hexylresorcinol is used as an anthelmintic agent for roundworms and duodenum. 4-Alkenylresorcinol is also known to have a whitening effect (Patent Document 5).
４−アルキルレゾルシノールの製造方法としては、例えば特許文献４および特許文献６などに記載されている様に、飽和カルボン酸または飽和カルボン酸ハロゲン化物とレゾルシノールとを、塩化亜鉛または塩化アルミニウム等のルイス酸存在下でフリーデル・クラフツ反応させ、生成した４−アシルレゾルシノールを亜鉛アマルガム／塩酸で還元する方法が広く知られている。
しかしながら、この製造方法では、腐食性の高い塩化亜鉛または塩化アルミニウムをフリーデル・クラフツ反応剤として、また、有害なハロゲン化合物やニトロ化合物を反応溶媒として、さらには、有毒な水銀を還元反応の触媒として用いなければならないという問題がある。
As a method for producing 4-alkylresorcinol, for example, as described in Patent Document 4 and Patent Document 6, a saturated carboxylic acid or a saturated carboxylic acid halide and resorcinol are converted into a Lewis acid such as zinc chloride or aluminum chloride. A method of reducing the produced 4-acylresorcinol with zinc amalgam / hydrochloric acid by the Friedel-Crafts reaction in the presence is widely known.
However, in this production method, highly corrosive zinc chloride or aluminum chloride is used as a Friedel-Crafts reagent, harmful halogen compounds or nitro compounds are used as reaction solvents, and toxic mercury is used as a catalyst for the reduction reaction. There is a problem that must be used as.
特許文献７には、アルミナを触媒とし、レゾルシノールとｎ−へキサノールとを液相中、２００〜４００℃で反応させて４−ｎ−へキシルレゾルシノールを直接的に製造する方法が記載されている。
しかし、この方法では、長時間の高温条件が必要であり、副生成物も多い。
Patent Document 7 describes a method for directly producing 4-n-hexylresorcinol by reacting resorcinol and n-hexanol in a liquid phase at 200 to 400 ° C. using alumina as a catalyst. .
However, this method requires a high temperature condition for a long time, and there are many by-products.
特許文献８には、特定金属の酸化物および水酸化物から選ばれる一種以上を触媒として用い、アルコールを超臨界状態にしてレゾルシノールと反応させて４−アルキルレゾルシノールを製造する方法が記載されている。
しかし、この方法は超臨界状態とするために、高温・高圧条件（例えば３５０℃以上、５ＭＰａ以上）が必要であり、そのための装置が必要であるとともに危険を伴うという問題がある。
Patent Document 8 describes a method for producing 4-alkylresorcinol by using one or more selected from oxides and hydroxides of a specific metal as a catalyst and reacting with alcohol with resorcinol in a supercritical state. .
However, this method requires a high-temperature and high-pressure condition (for example, 350 ° C. or higher and 5 MPa or higher) in order to achieve a supercritical state.
その他にも、４−アルキルレゾルシノールあるいは４−アルケニルレゾルシノールの製造方法が多く報告されているが、上記の様な問題があったり、副生成物が多く精製が困難であったり、著しく収率が低いなどの理由から、工業的な製造コストが非常に高くなるという問題がある（特許文献９〜１１、非特許文献１〜６）。 In addition, although many production methods of 4-alkylresorcinol or 4-alkenylresorcinol have been reported, there are the above-mentioned problems, many by-products are difficult to purify, and the yield is extremely low. For these reasons, there is a problem that the industrial production cost becomes very high (Patent Documents 9 to 11 and Non-Patent Documents 1 to 6).
本発明の目的は、腐食性の高い物質や、有害または有毒な物質を用いることなく、比較的低温で工業的に有利に４−アルキルレゾルシノールおよび４−アルケニルレゾルシノールを製造することにある。 It is an object of the present invention to produce 4-alkylresorcinol and 4-alkenylresorcinol advantageously industrially at a relatively low temperature without using highly corrosive substances or harmful or toxic substances.
上記目的を達成するために本発明者らは鋭意研究を続け、その結果、レゾルシノールとアルケニルハライドとを塩基存在下で反応させて、４−アルケニルレゾルシノールを工業的に有利に製造できることを見出した。さらに、この４−アルケニルレゾルシノールを還元することにより、対応する４−アルキルレゾルシノールも工業的に有利に製造できることを見出し、本発明を完成するに至った。 In order to achieve the above object, the present inventors have continued intensive studies, and as a result, have found that 4-alkenyl resorcinol can be produced industrially advantageously by reacting resorcinol and alkenyl halide in the presence of a base. Furthermore, by reducing this 4-alkenyl resorcinol, it has been found that the corresponding 4-alkyl resorcinol can also be produced industrially advantageously, and the present invention has been completed.
すなわち、本発明は、レゾルシノールと、アリル位がハロゲンで置換されたアルケニルハライドＲ２−Ｘ［Ｒ２は、炭素数１〜１２のアルコキシル基、フェニル基、又は複素環で置換されていてもよい炭素数３〜１２の鎖状、分岐又は環状アルケニル基、Ｘはハロゲンを示す。］とを、水中において塩基存在下で反応させ、アルケニルハライドをレゾルシノールに対して０．５倍モル当量以上２倍モル当量未満の範囲で用い、前記塩基はレゾルシノールに対して０．５〜２倍モル当量を用い、触媒としては前記塩基のみを用いることを特徴とする下記一般式（１）で表される４−アルケニルレゾルシノールの製造方法を提供する。
That is, in the present invention, resorcinol and an alkenyl halide R 2 —X [R 2 in which the allylic position is substituted with a halogen atom may be substituted with an alkoxyl group having 1 to 12 carbon atoms, a phenyl group, or a heterocyclic ring. A chain, branched or cyclic alkenyl group having 3 to 12 carbon atoms, X represents halogen. ] And is reacted in the presence of a base in water, 0.5 to 2 times the alkenyl halide used in the range of 2-fold molar equivalent weight less than 0.5 molar equivalents or more with respect to resorcinol, the base is to resorcinol- Provided is a method for producing 4-alkenylresorcinol represented by the following general formula (1), characterized by using a molar equivalent and using only the base as a catalyst .
また、本発明は、前記方法において、塩基がアルカリ金属又はアルカリ土類金属水酸化物であることを特徴とする４−アルケニルレゾルシノールの製造方法を提供する。
また、本発明は、前記方法により前記一般式（１）の４−アルケニルレゾルシノールを製造し、次いで該４−アルケニルレゾルシノールのアルケニル基を還元することを特徴とする下記一般式（２）で表される４−アルキルレゾルシノールの製造方法を提供する。
The present invention also provides a method for producing 4-alkenyl resorcinol, characterized in that, in the above method, the base is an alkali metal or alkaline earth metal hydroxide.
Further, the present invention is represented by the following general formula (2), wherein the 4-alkenyl resorcinol of the general formula (1) is produced by the above method, and then the alkenyl group of the 4-alkenyl resorcinol is reduced. A method for producing 4-alkylresorcinol is provided.
また、本発明は、前記方法において、４−アルケニルレゾルシノールの還元を、Ｐｄ−Ｃ触媒下、接触還元により行うことを特徴とする４−アルキルレゾルシノールの製造方法を提供する。
Moreover, this invention provides the manufacturing method of 4-alkyl resorcinol characterized by performing reduction | restoration of 4-alkenyl resorcinol by a catalytic reduction under a Pd-C catalyst in the said method.
本発明の製造方法によれば、レゾルシノールから腐食性の高い物質や、有害または有毒な物質を用いることなく、比較的低温で工業的に有利に４−アルキルレゾルシノールおよび４−アルケニルレゾルシノールを製造することができる。 According to the production method of the present invention, 4-alkylresorcinol and 4-alkenylresorcinol are advantageously produced industrially at a relatively low temperature without using a highly corrosive substance or a harmful or toxic substance from resorcinol. Can do.
４−アルケニルレゾルシノールの製造方法
本発明においては、出発原料であるレゾルシノールに、アルケニルハライドＲ２−Ｘを塩基存在下に反応させて、前記一般式（１）の４−アルケニルレゾルシノールを得る。
本発明においてＲ２で示される「アルケニル」とは、炭素数３〜１２の少なくとも一つの二重結合を有する脂肪族炭化水素基を意味する。該アルケニル基は、直鎖状、分岐状、環状の何れでもよい。また、アルケニル基は炭素数１〜３のアルコキシ基、ベンゼン環、又は複素環で置換されていてもよい。
Method for Producing 4-Alkenyl Resorcinol In the present invention, resorcinol as a starting material is reacted with alkenyl halide R 2 -X in the presence of a base to obtain 4-alkenyl resorcinol of the above general formula (1).
In the present invention, “alkenyl” represented by R 2 means an aliphatic hydrocarbon group having at least one double bond having 3 to 12 carbon atoms. The alkenyl group may be linear, branched or cyclic. The alkenyl group may be substituted with an alkoxy group having 1 to 3 carbon atoms, a benzene ring, or a heterocyclic ring.
アルケニルハライドとしては、アリル位がハロゲンで置換されたアルケニルハライドが挙げられ、例えば、３−クロロ−１−プロペン、３−ブロモ−１−プロペン、３−ヨード−１−プロペン、１−クロロ−２−ブテン、１−ブロモ−２−ブテン、１−ヨード−２−ブテン、１−クロロ−２−ペンテン、１−ブロモ−２−ペンテン、１−ヨード−２−ペンテン、１−クロロ−２−ヘキセン、１−ブロモ−２−ヘキセン、１−ヨード−２−ヘキセン、１−クロロ−２−ヘプテン、１−ブロモ−２−ヘプテン、１−ヨード−２−ヘプテン、１−クロロ−２−オクテン、１−ブロモ−２−オクテン、１−ヨード−２−オクテン、３−クロロ−２−メチル−１−プロペン、３−ブロモ−２−メチル−１−プロペン、３−ヨード−２−メチル−１−プロペン、１−クロロ−３−メチル−２−ブテン、１−ブロモ−３−メチル−２−ブテン、１−ヨード−３−メチル−２−ブテン、３−クロロ−１−フェニル−１−プロペン、３−ブロモ−１−フェニル−１−プロペン、３−ヨード−１−フェニル−１−プロペン、３−クロロ−２−メトキシプロペン、３−ブロモ−２−メトキシプロペン、３−ヨード−２−メトキシプロペン、１−クロロ−５−メトキシ−２−ペンテン、１−ブロモ−５−メトキシ−２−ペンテン、１−ヨード−５−メトキシ−２−ペンテン、３−クロロ−１−ブテン、３−ブロモ−１−ブテン、３−ヨード−１−ブテン、４−クロロ−２−ペンテン、４−ブロモ−２−ペンテン、４−ヨード−２−ペンテン、３−クロロシクロヘキセン、３−ブロモシクロヘキセン、３−ヨードシクロヘキセン、３−クロロ−５−メトキシ−１−ペンテン、３−ブロモ−５−メトキシ−１−ペンテン、３−ヨード−５−メトキシ−１−ペンテン、３−クロロ−３−メチル−１−ブテン、３−ブロモ−３−メチル−１−ブテン、３−ヨード−３−メチル−１−ブテン、４−クロロ−２，４−ジメチル−２−ペンテン、４−ブロモ−２，４−ジメチル−２−ペンテン、４−ヨード−２，４−ジメチル−２−ペンテン、１−クロロ−３，７−ジメチル−２，６−オクタジエン、１−ブロモ−３，７−ジメチル−２，６−オクタジエン、１−ヨード−３，７−ジメチル−２，６−オクタジエン等が挙げられる。 Examples of the alkenyl halide include alkenyl halides in which the allylic position is substituted with halogen, such as 3-chloro-1-propene, 3-bromo-1-propene, 3-iodo-1-propene, and 1-chloro-2. -Butene, 1-bromo-2-butene, 1-iodo-2-butene, 1-chloro-2-pentene, 1-bromo-2-pentene, 1-iodo-2-pentene, 1-chloro-2-hexene 1-bromo-2-hexene, 1-iodo-2-hexene, 1-chloro-2-heptene, 1-bromo-2-heptene, 1-iodo-2-heptene, 1-chloro-2-octene, 1 -Bromo-2-octene, 1-iodo-2-octene, 3-chloro-2-methyl-1-propene, 3-bromo-2-methyl-1-propene, 3-iodo-2-methyl-1-pro 1-chloro-3-methyl-2-butene, 1-bromo-3-methyl-2-butene, 1-iodo-3-methyl-2-butene, 3-chloro-1-phenyl-1-propene, 3-bromo-1-phenyl-1-propene, 3-iodo-1-phenyl-1-propene, 3-chloro-2-methoxypropene, 3-bromo-2-methoxypropene, 3-iodo-2-methoxypropene 1-chloro-5-methoxy-2-pentene, 1-bromo-5-methoxy-2-pentene, 1-iodo-5-methoxy-2-pentene, 3-chloro-1-butene, 3-bromo-1 -Butene, 3-iodo-1-butene, 4-chloro-2-pentene, 4-bromo-2-pentene, 4-iodo-2-pentene, 3-chlorocyclohexene, 3-bromocyclohexene, 3-iodo Cyclohexene, 3-chloro-5-methoxy-1-pentene, 3-bromo-5-methoxy-1-pentene, 3-iodo-5-methoxy-1-pentene, 3-chloro-3-methyl-1-butene, 3-bromo-3-methyl-1-butene, 3-iodo-3-methyl-1-butene, 4-chloro-2,4-dimethyl-2-pentene, 4-bromo-2,4-dimethyl-2- Pentene, 4-iodo-2,4-dimethyl-2-pentene, 1-chloro-3,7-dimethyl-2,6-octadiene, 1-bromo-3,7-dimethyl-2,6-octadiene, 1- And iodo-3,7-dimethyl-2,6-octadiene.
このうち、好適なアルケニルハライドとして、Ｒ３−ＣＲ４＝ＣＲ５−ＣＨ２−Ｘで示される基本構造を有するアリルハライド［Ｒ３〜Ｒ５はそれぞれ所望のＲ２−Ｘに対応して設定される基］が挙げられ、例えば、３−クロロ−１−プロペン、３−ブロモ−１−プロペン、１−クロロ−２−ブテン、１−ブロモ−２−ブテン、１−クロロ−２−ペンテン、１−ブロモ−２−ペンテン、１−クロロ−２−ヘキセン、１−ブロモ−２−ヘキセン、３−クロロ−２−メチル−１−プロペン、３−ブロモ−２−メチル−１−プロペンが好ましい。 Among these, as preferred alkenyl halides, allyl halides having a basic structure represented by R 3 —CR 4 ═CR 5 —CH 2 —X [R 3 to R 5 are respectively set corresponding to desired R 2 —X. Group, for example, 3-chloro-1-propene, 3-bromo-1-propene, 1-chloro-2-butene, 1-bromo-2-butene, 1-chloro-2-pentene, 1-bromo-2-pentene, 1-chloro-2-hexene, 1-bromo-2-hexene, 3-chloro-2-methyl-1-propene and 3-bromo-2-methyl-1-propene are preferred.
アルケニルハライドは、レゾルシノールに対して０．５倍モル当量以上２倍モル当量未満、さらには１〜１．５倍モル当量とすることが好ましい。アルケニルハライドが少なすぎると反応が不十分となり、多すぎると副生成物が著しく増大して精製が困難となる。 The alkenyl halide is preferably 0.5-fold molar equivalent or more and less than 2-fold molar equivalent, more preferably 1 to 1.5-fold molar equivalent to resorcinol. If the amount of alkenyl halide is too small, the reaction becomes insufficient. If the amount is too large, the by-products are remarkably increased and purification becomes difficult.
反応に用いる塩基としては、水酸化ナトリウム、水酸化カリウム、水酸化リチウム等のアルカリ金属水酸化物；水酸化バリウム、水酸化カルシウム、水酸化マグネシウム等のアルカリ土類金属水酸化物；ナトリウムメトキシド、ナトリウムエトキシド、カリウムｔ−ブトキシド等の金属アルコキシド；水酸化テトラブチルアンモニウム、水酸化ベンジルトリメチルメチルアンモニウム等の水酸化テトラアルキルアンモニウム；炭酸カリウム、炭酸ナトリウム、炭酸カルシウム、炭酸水素ナトリウム、炭酸水素カリウム等の金属炭酸塩；水素化ナトリウム、水素化カリウム、水素化カルシウム等の金属水素化物；ナトリウム、カリウム、リチウム等のアルカリ金属；トリエチルエチルアミン、ジエチルアミン、１，８−ジアザビシクロ[５．４．０]ウンデセン、１，５−ジアザビシクロ[４．３．０]ノネン等のアミン類等；及びこれらの混合物が挙げられる。
このうち、水酸化ナトリウム、水酸化カリウム、水酸化リチウム等のアルカリ金属水酸化物や、水酸化バリウム、水酸化カルシウム、水酸化マグネシウム等のアルカリ土類金属水酸化物が好ましい。
塩基の量としては、例えば、レゾルシノールに対して０．１〜５倍モル当量とすることができるが、収率の点から、好ましくは０．５〜２倍モル当量、さらに好ましくは０．８〜１．２倍モル当量である。
Examples of the base used in the reaction include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide; alkaline earth metal hydroxides such as barium hydroxide, calcium hydroxide and magnesium hydroxide; sodium methoxide Metal alkoxides such as sodium ethoxide and potassium t-butoxide; tetraalkylammonium hydroxides such as tetrabutylammonium hydroxide and benzyltrimethylmethylammonium hydroxide; potassium carbonate, sodium carbonate, calcium carbonate, sodium bicarbonate, potassium bicarbonate Metal carbonates such as sodium hydride, potassium hydride, calcium hydride; alkali metals such as sodium, potassium, lithium; triethylethylamine, diethylamine, 1,8-diazabicyclo [5.4. 0] undecene, amines such as 1,5-diazabicyclo [4.3.0] nonene, and the like; and mixtures thereof.
Among these, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and lithium hydroxide, and alkaline earth metal hydroxides such as barium hydroxide, calcium hydroxide, and magnesium hydroxide are preferable.
The amount of the base can be, for example, 0.1 to 5 molar equivalents with respect to resorcinol, but preferably 0.5 to 2 molar equivalents, more preferably 0.8 from the viewpoint of yield. -1.2 times molar equivalent.
本アルケニル化反応は、反応溶媒を用いて液相中で行うことが好ましい。反応溶媒としては、反応に悪影響を及ぼさない限り特に限定されない。例えば、トルエン、キシレン、ベンゼン、ヘキサン、シクロヘキサン等の炭化水素系溶媒；メタノール、エタノール、イソプロピルアルコール等のアルコール系溶媒；テトラヒドロフラン；ジメチルホルムアミド；ジメチルスルホキシド；水；及びこれらの混合溶媒などが挙げられるが、好ましくは水、アルコール系溶媒であり、特に好ましくは水である。無溶媒で反応を行うことも可能であるが、副生成物が増大し、収率が低下することがある。 The alkenylation reaction is preferably performed in a liquid phase using a reaction solvent. The reaction solvent is not particularly limited as long as it does not adversely affect the reaction. Examples thereof include hydrocarbon solvents such as toluene, xylene, benzene, hexane and cyclohexane; alcohol solvents such as methanol, ethanol and isopropyl alcohol; tetrahydrofuran; dimethylformamide; dimethyl sulfoxide; water; and a mixed solvent thereof. , Preferably water or an alcohol solvent, and particularly preferably water. Although it is possible to carry out the reaction without solvent, by-products may increase and the yield may decrease.
本アルケニル化反応は、水又は含水アルコールなどの水性溶媒中で好適に行うことができ、特に水中で効率的に進行する。近年の合成反応においては、環境適合性の点から水中での反応が強く望まれている。本発明の方法はこのような要請にも応えることができるものである。
また、溶媒として水を用いれば、少量の溶媒でレゾルシノールや無機塩基を溶解状態で効率的に反応させることができ、反応設備も省スペース化できるという点でも工業的に非常に有利である。
This alkenylation reaction can be suitably carried out in an aqueous solvent such as water or a hydrous alcohol, and particularly proceeds efficiently in water. In recent synthetic reactions, reaction in water is strongly desired from the viewpoint of environmental compatibility. The method of the present invention can meet such a demand.
Moreover, if water is used as a solvent, resorcinol and an inorganic base can be efficiently reacted in a dissolved state with a small amount of solvent, and the reaction equipment can be saved in space, which is very advantageous industrially.
反応温度は、０〜２００℃の範囲で行うことができるが、好ましくは室温（２０℃）から１００℃の範囲である。また、反応は加圧下で行うこともできるが、通常は大気圧下で行えばよい。 Although reaction temperature can be performed in the range of 0-200 degreeC, Preferably it is the range of room temperature (20 degreeC) to 100 degreeC. Further, the reaction can be carried out under pressure, but usually it may be carried out under atmospheric pressure.
４−アルキルレゾルシノールの製造
さらに、本発明においては、このようにして得られた４−アルケニルレゾルシノールのアルケニル基を還元することにより、前記一般式（２）の４−アルキルレゾルシノールを得る。
還元反応としては、一般的な炭素−炭素二重結合の還元反応を用いることができる。このうち最も一般的なのは接触水素添加反応であり、触媒としては白金、パラジウム、ロジウム、ルテニウム等の貴金属触媒、ニッケル、銅−クロム系触媒等が挙げられる。具体的には、例えば、エタノール、酢酸エチル等の溶媒中、触媒としてパラジウム-炭素を用い、水素ガス雰囲気下、室温から溶媒の還流温度の範囲で反応を行うことにより目的を達する。この場合、アルケニルレゾルシノールからほぼ１００％の収率で対応するアルキルレゾルシノールを得ることができる。
Production of 4-alkylresorcinol Further, in the present invention, the alkenyl group of 4-alkenylresorcinol thus obtained is reduced to obtain 4-alkylresorcinol of the above general formula (2).
As the reduction reaction, a general carbon-carbon double bond reduction reaction can be used. Of these, the most common is a catalytic hydrogenation reaction, and examples of the catalyst include noble metal catalysts such as platinum, palladium, rhodium, and ruthenium, nickel, and copper-chromium catalysts. Specifically, for example, the object is achieved by performing reaction in a solvent such as ethanol or ethyl acetate using palladium-carbon as a catalyst in a hydrogen gas atmosphere in the range of room temperature to the reflux temperature of the solvent. In this case, the corresponding alkyl resorcinol can be obtained from alkenyl resorcinol in almost 100% yield.
本発明の製造方法において反応終了後の反応混合物には、４−アルケニルレゾルシノール又は４−アルキルレゾルシノールのほかに、未反応の原料、副反応による生成物が含まれることもある。各種の用途に必要な純度まで、４−アルケニルレゾルシノール又は４−アルキルレゾルシノールを精製することができる。精製の方法は、特に限定されず、蒸留、抽出、晶析等の通常工業的に使用できる方法が適用できる。 In the production method of the present invention, the reaction mixture after completion of the reaction may contain, in addition to 4-alkenyl resorcinol or 4-alkyl resorcinol, unreacted raw materials and products from side reactions. 4-Alkenylresorcinol or 4-alkylresorcinol can be purified to the purity required for various applications. The purification method is not particularly limited, and a method that can be usually used industrially, such as distillation, extraction, and crystallization, can be applied.
以下、具体例を挙げてさらに本発明を説明するが、これらに限定されるものではない。 Hereinafter, the present invention will be further described with specific examples, but is not limited thereto.
実施例１ 4-（2-メチルアリル）レゾルシノールの製造（１）
水酸化ナトリウム（和光純薬製、試薬特級） (4.64 g, 0.116 mol) を水 (25 ml) に室温にて溶解後、レゾルシノール（関東化学製、試薬特級） (12.77 g, 0.116 mol) を一括で加え、60℃で5分間撹拌して溶解させた。60℃にて3-クロロ-2-メチル-1-プロペン（東京化成製、純度95.0%以上） (11.29 ml, 0.116 mol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (50 ml) を加えて有機層と水層（１番目）に分配した。この有機層に1N水酸化ナトリウム (30 ml) を加えて有機層と水層（２番目）に分配した。この操作をさらに５回繰り返した。得られた有機層および水層（１番目〜７番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（３番目〜７番目）に酢酸エチル (50 ml) および12N 塩酸 (10 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (9.86 g) を得た。
1H-NMR (CDCl3)δ: 1.72 (3H, S), 3.29 (2H, s), 4.83 (1H, s), 4.89 (1H, s), 5.41 -5.68 (2H, m), 6.35 ? 6.39 (2H, m), 6.92 (1H, d, J=9.2 Hz).
Example 1 Production of 4- (2-methylallyl) resorcinol (1)
Sodium hydroxide (made by Wako Pure Chemicals, reagent grade) (4.64 g, 0.116 mol) is dissolved in water (25 ml) at room temperature, and then resorcinol (made by Kanto Chemical Co., reagent grade) (12.77 g, 0.116 mol) is batched. And dissolved by stirring at 60 ° C. for 5 minutes. 3-Chloro-2-methyl-1-propene (manufactured by Tokyo Chemical Industry, purity 95.0% or more) (11.29 ml, 0.116 mol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 1N sodium hydroxide (30 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was further repeated 5 times. The obtained organic layer and aqueous layer (first to seventh) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (third to seventh), which was confirmed to contain the desired product, was added to ethyl acetate ( 50 ml) and 12N hydrochloric acid (10 ml) were added to the organic layer and the aqueous layer. This organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (9.86 g) of 4- (2-methylallyl) resorcinol as a black brown oil.
1 H-NMR (CDCl 3 ) δ: 1.72 (3H, S), 3.29 (2H, s), 4.83 (1H, s), 4.89 (1H, s), 5.41 -5.68 (2H, m), 6.35? 6.39 (2H, m), 6.92 (1H, d, J = 9.2 Hz).
実施例２ 4-イソブチルレゾルシノールの製造（１）
実施例１の4-（2-メチルアリル）レゾルシノールの粗生成物 (9.86 g) をエタノール (50 ml) に溶解させ、5%Pd-C（50%含水品）（エヌ・イー ケムキャット製、BNA-Type） (951 mg) を加えて水素置換後、室温にて9時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (9.82 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 122 - 124℃）して淡黄色オイル (8.68 g) を得た。この淡黄色オイルをエタノール (7 ml) に溶解させ、撹拌下の水 (140 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して白色ウェット晶 (8.27 g) を得た。この白色ウェット晶をn-ヘキサン (45 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して白色粉末状の4-イソブチルレゾルシノール (5.92 g) を得た。
1H-NMR (CDCl3)δ: 0.91 (6H, d, J=6.8 Hz), 1.86 (1H, 9重線, J=6.8 Hz), 2.39 (2H,d, J=6.8 Hz), 4.74 (1H, s), 4.77 (1H, s), 6.32 (1H, d, J=2.5 Hz), 6.35 (1H, dd, J=2.5, 8.2 Hz), 6.91 (1H, d, J=8.2 Hz).
Example 2 Production of 4-isobutylresorcinol (1)
The crude 4- (2-methylallyl) resorcinol product (9.86 g) of Example 1 was dissolved in ethanol (50 ml), and 5% Pd-C (50% water-containing product) (manufactured by N.E. Chemcat, BNA- Type) (951 mg) was added and the mixture was replaced with hydrogen, followed by stirring at room temperature for 9 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (9.82 g). This brown oil was distilled under reduced pressure (0.2 kPa, 122-124 ° C.) to obtain a pale yellow oil (8.68 g). This pale yellow oil was dissolved in ethanol (7 ml) and added dropwise to stirring water (140 ml). After seeding 4-isobutylresorcinol seed crystals, the mixture was stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain white wet crystals (8.27 g). The white wet crystals were suspended in n-hexane (45 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed and dried under reduced pressure to give 4-isobutylresorcinol (5.92 g) as a white powder.
1 H-NMR (CDCl 3 ) δ: 0.91 (6H, d, J = 6.8 Hz), 1.86 (1H, 9-wire, J = 6.8 Hz), 2.39 (2H, d, J = 6.8 Hz), 4.74 ( 1H, s), 4.77 (1H, s), 6.32 (1H, d, J = 2.5 Hz), 6.35 (1H, dd, J = 2.5, 8.2 Hz), 6.91 (1H, d, J = 8.2 Hz).
実施例３ 4-（2-メチルアリル）レゾルシノールの製造（２）
水酸化カリウム（和光純薬製、試薬特級） (5.09 g, 純度85%で換算した場合 77.2 mmol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。室温にて3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、室温で17時間撹拌した。反応液に酢酸エチル (50 ml) を加えて有機層と水層に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層に分配した。この操作を３回繰り返した。得られた有機層および水層（１番目〜５番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜５番目）に酢酸エチル (50 ml) および12N 塩酸 (10 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (8.73 g) を得た。
Example 3 Production of 4- (2-methylallyl) resorcinol (2)
Potassium hydroxide (made by Wako Pure Chemicals, reagent grade) (5.09 g, 77.2 mmol when converted to 85% purity) was dissolved in water (20 ml) at room temperature, and then resorcinol (10.00 g, 90.8 mmol) was batched. In addition, it was dissolved by stirring at room temperature for 10 minutes. 3-Chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was quickly added dropwise at room temperature, followed by stirring at room temperature for 17 hours. Ethyl acetate (50 ml) was added to the reaction solution, which was partitioned into an organic layer and an aqueous layer. 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer were partitioned. This operation was repeated three times. The obtained organic layer and aqueous layer (first to fifth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fifth) confirmed to contain the target product was added to ethyl acetate ( 50 ml) and 12N hydrochloric acid (10 ml) were added to the organic layer and the aqueous layer. This organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (8.73 g) of 4- (2-methylallyl) resorcinol in the form of a dark brown oil.
実施例４ 4-イソブチルレゾルシノールの製造（２）
実施例３の4-（2-メチルアリル）レゾルシノールの粗生成物 (8.73 g) をエタノール (20 ml) に溶解させ、5%Pd-C（50%含水品） (813 mg) を加えて水素置換後、室温にて3時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (8.87 g) を得た。この褐色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下30分間撹拌した。析出した結晶を濾取、洗浄して黄土色ウェット晶 (9.71 g) を得た。この黄土色ウェット晶をn-ヘキサン (60 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して淡黄色粉末状の4-イソブチルレゾルシノール (6.37 g) を得た。
Example 4 Production of 4-isobutylresorcinol (2)
The crude 4- (2-methylallyl) resorcinol product (8.73 g) of Example 3 was dissolved in ethanol (20 ml), and 5% Pd-C (50% water-containing product) (813 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (8.87 g). This brown oil was dissolved in ethanol (6 ml) and added dropwise to stirring water (100 ml). After seeding 4-isobutylresorcinol seed crystals, the mixture was stirred for 30 minutes under ice cooling. The precipitated crystals were collected by filtration and washed to give ocher wet crystals (9.71 g). The ocher wet crystals were suspended in n-hexane (60 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed and dried under reduced pressure to give 4-isobutylresorcinol (6.37 g) as a pale yellow powder.
実施例５ 4-（2-メチルアリル）レゾルシノールの製造（３）
水酸化ナトリウム (7.26 g, 0.182 mol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。60℃にて3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (50 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を１回繰り返した。得られた有機層および水層（１番目〜３番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（１番目〜３番目）に酢酸エチル (50 ml) および12N 塩酸 (6.7 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (6.31 g) を得た。
Example 5 Production of 4- (2-methylallyl) resorcinol (3)
After sodium hydroxide (7.26 g, 0.182 mol) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added all at once and dissolved by stirring for 10 minutes at room temperature. 3-Chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated once. The obtained organic layer and aqueous layer (first to third) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (first to third) confirmed to contain the target product was added to ethyl acetate ( 50 ml) and 12N hydrochloric acid (6.7 ml) were added to the organic layer and the aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (6.31 g) of 4- (2-methylallyl) resorcinol in the form of a dark brown oil.
実施例６ 4-イソブチルレゾルシノールの製造（３）
実施例５の4-（2-メチルアリル）レゾルシノールの粗生成物 (6.31 g) をエタノール (13 ml) に溶解させ、5%Pd-C（50%含水品） (599 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (6.45 g) を得た。この褐色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (80 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して黄土色ウェット晶 (5.56 g) を得た。この黄土色ウェット晶をn-ヘキサン (50 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して黄色粉末状の4-イソブチルレゾルシノール (2.16 g) を得た。
Example 6 Production of 4-isobutylresorcinol (3)
4- (2-methylallyl) resorcinol crude product (6.31 g) of Example 5 was dissolved in ethanol (13 ml), and 5% Pd-C (50% water-containing product) (599 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (6.45 g). This brown oil was dissolved in ethanol (6 ml) and added dropwise to stirring water (80 ml). After seeding 4-isobutylresorcinol seed crystals, the mixture was stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to give ocher wet crystals (5.56 g). The ocher wet crystals were suspended in n-hexane (50 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed, and dried under reduced pressure to give 4-isobutylresorcinol (2.16 g) as a yellow powder.
実施例７ 4-（2-メチルアリル）レゾルシノールの製造（４）
水酸化ナトリウム (1.82 g, 45.4 mmol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。室温にて3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、室温で18時間撹拌した。反応液に酢酸エチル (30 ml) を加えて有機層と水層（１番目）に分配した。この有機層に5N水酸化ナトリウム (10 ml) を加えて有機層と水層（２番目）に分配した。この操作を３回繰り返した。得られた有機層および水層（１番目〜５番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜５番目）に酢酸エチル (30 ml) および12N 塩酸 (12.5 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (8.01 g) を得た。
Example 7 Production of 4- (2-methylallyl) resorcinol (4)
After sodium hydroxide (1.82 g, 45.4 mmol) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added all at once and dissolved by stirring at room temperature for 10 minutes. 3-Chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was quickly added dropwise at room temperature, and the mixture was stirred at room temperature for 18 hours. Ethyl acetate (30 ml) was added to the reaction mixture, and the mixture was partitioned into an organic layer and an aqueous layer (first). 5N sodium hydroxide (10 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated three times. The obtained organic layer and aqueous layer (first to fifth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fifth) confirmed to contain the target product was added to ethyl acetate ( 30 ml) and 12N hydrochloric acid (12.5 ml) were added to the organic layer and the aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (8.01 g) of 4- (2-methylallyl) resorcinol in the form of a dark brown oil.
実施例８ 4-イソブチルレゾルシノールの製造（４）
実施例７の4-（2-メチルアリル）レゾルシノールの粗生成物 (8.01 g) をエタノール (16 ml) に溶解させ、5%Pd-C（50%含水品） (403 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (7.53 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 120 - 129℃）して薄茶色オイル (6.48 g) を得た。この薄茶色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して黄色ウェット晶 (4.27 g) を得た。この黄色ウェット晶をn-ヘキサン (50 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して淡黄色粉末状の4-イソブチルレゾルシノール (2.92 g) を得た。
Example 8 Production of 4-isobutylresorcinol (4)
The crude 4- (2-methylallyl) resorcinol product (8.01 g) of Example 7 was dissolved in ethanol (16 ml), and 5% Pd-C (50% water-containing product) (403 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (7.53 g). This brown oil was distilled under reduced pressure (0.2 kPa, 120-129 ° C.) to obtain a light brown oil (6.48 g). This light brown oil was dissolved in ethanol (6 ml), dropped into stirring water (100 ml), seeded with 4-isobutylresorcinol seed crystals, and stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain yellow wet crystals (4.27 g). The yellow wet crystals were suspended in n-hexane (50 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed and dried under reduced pressure to give 4-isobutylresorcinol (2.92 g) as a pale yellow powder.
実施例９ 4-（2-メチルアリル）レゾルシノールの製造（５）
水酸化カリウム (5.99 g, 純度85%で換算した場合 90.8 mmol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。60℃にて3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (50 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を３回繰り返した。得られた有機層および水層（１番目〜５番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜５番目）に酢酸エチル (30 ml) および12N 塩酸 (10 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (9.09 g) を得た。
Example 9 Production of 4- (2-methylallyl) resorcinol (5)
Potassium hydroxide (5.99 g, 90.8 mmol when converted to a purity of 85%) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added all at once, and the mixture was stirred at room temperature for 10 minutes. Dissolved. 3-Chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated three times. The obtained organic layer and aqueous layer (first to fifth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fifth) confirmed to contain the target product was added to ethyl acetate ( 30 ml) and 12N hydrochloric acid (10 ml) were added to the organic layer and the aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (9.09 g) of 4- (2-methylallyl) resorcinol as a black brown oil.
実施例１０ 4-イソブチルレゾルシノールの製造（５）
実施例９の4-（2-メチルアリル）レゾルシノールの粗生成物 (9.09 g) をエタノール (18 ml) に溶解させ、5%Pd-C（50%含水品） (444 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (8.51 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 120 - 124℃）してオレンジ色オイル (7.41 g) を得た。このオレンジ色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して黄色ウェット晶 (7.26 g) を得た。この黄色ウェット晶をn-ヘキサン (60 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して白色粉末状の4-イソブチルレゾルシノール (3.94 g) を得た。
Example 10 Production of 4-isobutylresorcinol (5)
The crude 4- (2-methylallyl) resorcinol product (9.09 g) of Example 9 was dissolved in ethanol (18 ml), and 5% Pd-C (50% water-containing product) (444 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (8.51 g). This brown oil was distilled under reduced pressure (0.2 kPa, 120-124 ° C.) to obtain an orange oil (7.41 g). This orange oil was dissolved in ethanol (6 ml) and added dropwise to stirring water (100 ml). After seeding 4-isobutylresorcinol seed crystals, the mixture was stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain yellow wet crystals (7.26 g). The yellow wet crystals were suspended in n-hexane (60 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed and dried under reduced pressure to obtain 4-isobutylresorcinol (3.94 g) as a white powder.
実施例１１ 4-（2-メチルアリル）レゾルシノールの製造（６）
水酸化カリウム (4.80 g, 純度85%で換算した場合 72.7 mmol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。60℃にて3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (50 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を３回繰り返した。得られた有機層および水層（１番目〜５番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜５番目）に酢酸エチル (30 ml) および12N 塩酸 (10 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (9.37 g) を得た。
Example 11 Production of 4- (2-methylallyl) resorcinol (6)
Potassium hydroxide (4.80 g, 72.7 mmol when converted to 85% purity) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added in one batch, and the mixture was stirred at room temperature for 10 minutes. Dissolved. 3-Chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated three times. The obtained organic layer and aqueous layer (first to fifth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fifth) confirmed to contain the target product was added to ethyl acetate ( 30 ml) and 12N hydrochloric acid (10 ml) were added to the organic layer and the aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (9.37 g) of 4- (2-methylallyl) resorcinol as a black brown oil.
実施例１２ 4-イソブチルレゾルシノールの製造（６）
実施例１１の4-（2-メチルアリル）レゾルシノールの粗生成物 (9.37 g) をエタノール (18 ml) に溶解させ、5%Pd-C（50%含水品） (481 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (8.67 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 120 - 124℃）して黄色オイル (7.51 g) を得た。この黄色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して白色ウェット晶 (7.15 g) を得た。この白色ウェット晶をn-ヘキサン (60 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して白色粉末状の4-イソブチルレゾルシノール (4.10 g) を得た。
Example 12 Production of 4-isobutylresorcinol (6)
The crude 4- (2-methylallyl) resorcinol product (9.37 g) of Example 11 was dissolved in ethanol (18 ml), and 5% Pd-C (50% water-containing product) (481 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (8.67 g). This brown oil was distilled under reduced pressure (0.2 kPa, 120-124 ° C.) to obtain a yellow oil (7.51 g). This yellow oil was dissolved in ethanol (6 ml), added dropwise to stirring water (100 ml), seeded with 4-isobutylresorcinol seed crystals, and then stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain white wet crystals (7.15 g). The white wet crystals were suspended in n-hexane (60 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed and dried under reduced pressure to give 4-isobutylresorcinol (4.10 g) as a white powder.
実施例１３ 4-（2-メチルアリル）レゾルシノールの製造（７）
水酸化カリウム (7.19 g, 純度85%で換算した場合 0.109 mol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。60℃にて3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (50 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を２回繰り返した。得られた有機層および水層（１番目〜４番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜４番目）に酢酸エチル (30 ml) および12N 塩酸 (6.7 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (7.51 g) を得た。
Example 13 Production of 4- (2-methylallyl) resorcinol (7)
Potassium hydroxide (7.19 g, 0.109 mol when converted to a purity of 85%) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added in a lump and stirred at room temperature for 10 minutes. Dissolved. 3-Chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated twice. The obtained organic layer and aqueous layer (first to fourth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fourth), which was confirmed to contain the desired product, was added to ethyl acetate ( 30 ml) and 12N hydrochloric acid (6.7 ml) were added, and the mixture was partitioned into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (7.51 g) of 4- (2-methylallyl) resorcinol as a black brown oil.
実施例１４ 4-イソブチルレゾルシノールの製造（７）
実施例１３の4-（2-メチルアリル）レゾルシノールの粗生成物 (7.51 g) をエタノール (15 ml) に溶解させ、5%Pd-C（50%含水品） (360 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (6.37 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 120 - 124℃）してオレンジ色オイル (5.68 g) を得た。このオレンジ色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して淡黄色ウェット晶 (6.22 g) を得た。この淡黄色ウェット晶をn-ヘキサン (60 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して白色粉末状の4-イソブチルレゾルシノール (3.91 g) を得た。
Example 14 Production of 4-isobutylresorcinol (7)
The crude 4- (2-methylallyl) resorcinol product (7.51 g) of Example 13 was dissolved in ethanol (15 ml), and 5% Pd-C (50% water-containing product) (360 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (6.37 g). This brown oil was distilled under reduced pressure (0.2 kPa, 120-124 ° C.) to obtain an orange oil (5.68 g). This orange oil was dissolved in ethanol (6 ml) and added dropwise to stirring water (100 ml). After seeding 4-isobutylresorcinol seed crystals, the mixture was stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain pale yellow wet crystals (6.22 g). The pale yellow wet crystals were suspended in n-hexane (60 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed, and dried under reduced pressure to obtain 4-isobutylresorcinol (3.91 g) as a white powder.
実施例１５ 4-（2-メチルアリル）レゾルシノールの製造（８）
水酸化ナトリウム (3.63 g, 90.8 mmol) およびレゾルシノール (10.00 g, 90.8 mmol) をメタノール (20 ml) に60℃にて溶解させ、3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を減圧濃縮後、酢酸エチル (50 ml) と水 (30 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を３回繰り返した。得られた有機層および水層（１番目〜５番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜５番目）に酢酸エチル (30 ml) および12N 塩酸 (10 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (6.24 g) を得た。
Example 15 Production of 4- (2-methylallyl) resorcinol (8)
Sodium hydroxide (3.63 g, 90.8 mmol) and resorcinol (10.00 g, 90.8 mmol) were dissolved in methanol (20 ml) at 60 ° C, and 3-chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was dissolved. ) Was quickly added dropwise, followed by stirring at 60 ° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate (50 ml) and water (30 ml) were added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated three times. The obtained organic layer and aqueous layer (first to fifth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fifth) confirmed to contain the target product was added to ethyl acetate ( 30 ml) and 12N hydrochloric acid (10 ml) were added to the organic layer and the aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (6.24 g) of 4- (2-methylallyl) resorcinol in the form of a dark brown oil.
実施例１６ 4-イソブチルレゾルシノールの製造（８）
実施例１５の4-（2-メチルアリル）レゾルシノールの粗生成物 (6.24 g) をエタノール (6 ml) に溶解させ、5%Pd-C（50%含水品） (317 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (5.87 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 115 - 124℃）してオレンジ色オイル (4.01 g) を得た。このオレンジ色オイルをエタノール (4 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して淡黄色ウェット晶 (2.89 g) を得た。この淡黄色ウェット晶をn-ヘキサン (30 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して白色粉末状の4-イソブチルレゾルシノール (1.99 g) を得た。
Example 16 Production of 4-isobutylresorcinol (8)
The crude 4- (2-methylallyl) resorcinol product (6.24 g) of Example 15 was dissolved in ethanol (6 ml), and 5% Pd-C (50% water-containing product) (317 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (5.87 g). This brown oil was distilled under reduced pressure (0.2 kPa, 115-124 ° C.) to obtain an orange oil (4.01 g). This orange oil was dissolved in ethanol (4 ml), dropped into stirring water (100 ml), seeded with 4-isobutylresorcinol seed crystals, and stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain pale yellow wet crystals (2.89 g). The pale yellow wet crystals were suspended in n-hexane (30 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed, and dried under reduced pressure to give 4-isobutylresorcinol (1.99 g) as a white powder.
実施例１７ 4-（2-メチルアリル）レゾルシノールの製造（９）
水酸化ナトリウム (3.63 g, 90.8 mmol) およびレゾルシノール (10.00 g, 90.8 mmol) をエタノール (20 ml) に60℃にて懸濁させ、3-クロロ-2-メチル-1-プロペン (8.84 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を減圧濃縮後、酢酸エチル (50 ml) と水 (30 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を２回繰り返した。得られた有機層および水層（１番目〜４番目）を薄層シリカゲルカラムクロマトグラフィーで分析して、目的物が含まれることが確認された水層（２番目〜４番目）に酢酸エチル (30 ml) および12N 塩酸 (6.7 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して黒褐色オイル状の4-（2-メチルアリル）レゾルシノールの粗生成物 (6.16 g) を得た。
Example 17 Production of 4- (2-methylallyl) resorcinol (9)
Sodium hydroxide (3.63 g, 90.8 mmol) and resorcinol (10.00 g, 90.8 mmol) were suspended in ethanol (20 ml) at 60 ° C, and 3-chloro-2-methyl-1-propene (8.84 ml, 90.8 mmol) was suspended. mmol) was rapidly added dropwise, followed by stirring at 60 ° C. for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate (50 ml) and water (30 ml) were added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated twice. The obtained organic layer and aqueous layer (first to fourth) were analyzed by thin layer silica gel column chromatography, and the aqueous layer (second to fourth), which was confirmed to contain the desired product, was added to ethyl acetate ( 30 ml) and 12N hydrochloric acid (6.7 ml) were added, and the mixture was partitioned into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product (6.16 g) of 4- (2-methylallyl) resorcinol in the form of a dark brown oil.
実施例１８ 4-イソブチルレゾルシノールの製造（９）
実施例１７の4-（2-メチルアリル）レゾルシノールの粗生成物 (5.16 g) をエタノール (6.5 ml) に溶解させ、5%Pd-C（50%含水品） (327 mg) を加えて水素置換後、室温にて4時間撹拌した。反応液をセライト濾過後、濃縮して褐色オイル (5.57 g) を得た。この褐色オイルを減圧蒸留（0.2 kPa, 118 - 126℃）してオレンジ色オイル (5.38 g) を得た。このオレンジ色オイルをエタノール (6 ml) に溶解させ、撹拌下の水 (100 ml) に滴下し、4-イソブチルレゾルシノールの種晶を接種後、氷冷下1時間撹拌した。析出した結晶を濾取、洗浄して淡黄色ウェット晶 (3.76 g) を得た。この淡黄色ウェット晶をn-ヘキサン (50 ml) に懸濁させ、室温にて30分間撹拌した。結晶を濾取、洗浄、減圧乾燥して白色粉末状の4-イソブチルレゾルシノール (2.86 g) を得た。
Example 18 Production of 4-isobutylresorcinol (9)
The crude 4- (2-methylallyl) resorcinol product (5.16 g) of Example 17 was dissolved in ethanol (6.5 ml), and 5% Pd-C (50% water-containing product) (327 mg) was added to replace the hydrogen. Thereafter, the mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite and concentrated to give a brown oil (5.57 g). This brown oil was distilled under reduced pressure (0.2 kPa, 118-126 ° C.) to obtain an orange oil (5.38 g). This orange oil was dissolved in ethanol (6 ml) and added dropwise to stirring water (100 ml). After seeding 4-isobutylresorcinol seed crystals, the mixture was stirred for 1 hour under ice cooling. The precipitated crystals were collected by filtration and washed to obtain pale yellow wet crystals (3.76 g). The pale yellow wet crystals were suspended in n-hexane (50 ml) and stirred at room temperature for 30 minutes. The crystals were collected by filtration, washed, and dried under reduced pressure to give 4-isobutylresorcinol (2.86 g) as a white powder.
実施例１９ 4-（2-メチルアリル）レゾルシノールの製造（１０）
水酸化ナトリウム (3.63 g, 90.8 mmol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。60℃にて3-クロロ-2-メチル-1-プロペン (17.7 ml, 0.182 mol) を素早く滴下後、60℃で3時間撹拌した。反応液を薄層シリカゲルカラムクロマトグラフィーで分析した結果、多様な副生成物が大量に生成して目的物の生成が僅かであったため、反応処理を中止した。
このように、過剰なアルケニルハライドは収率を著しく低下させる。また、アルケニルハライドが少なすぎると収率が低下する。本発明者らの検討によれば、アルケニルハライドはレゾルシノールに対して０．５倍モル当量以上２倍モル当量未満、さらには１〜１．５倍モル当量とすることが好適である。
Example 19 Production of 4- (2-methylallyl) resorcinol (10)
After sodium hydroxide (3.63 g, 90.8 mmol) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added all at once and dissolved by stirring at room temperature for 10 minutes. 3-Chloro-2-methyl-1-propene (17.7 ml, 0.182 mol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction solution was analyzed by thin layer silica gel column chromatography. As a result, a large amount of various by-products were produced, and the production of the target product was slight. Therefore, the reaction treatment was stopped.
Thus, excess alkenyl halide significantly reduces the yield. Moreover, when there is too little alkenyl halide, a yield will fall. According to the study by the present inventors, it is preferable that the alkenyl halide is 0.5 times molar equivalent or more and less than 2 times molar equivalent, more preferably 1 to 1.5 times molar equivalent to resorcinol.
比較例１ 直接的アルキル化（１）
水酸化ナトリウム (726 mg, 18.2 mmol) を水 (4 ml) に室温にて溶解後、レゾルシノール (2.00 g, 18.2 mmol) を一括で加え、60℃で2分間撹拌して溶解させた。60℃にて1-クロロ-2-メチルプロパン（東京化成製、純度98.0%以上） (1.91 ml, 18.2 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (10 ml) および12N 塩酸 (2 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して茶色固体 (2.12 g) を得た。この茶色固体をシリカゲルカラムクマトグラフィー (シリカゲル 30 g, n-ヘキサン：酢酸エチル＝２：１) にて精製を行い、黄土色固体のレゾルシノール (1.95 g) を得た。
Comparative Example 1 Direct alkylation (1)
After sodium hydroxide (726 mg, 18.2 mmol) was dissolved in water (4 ml) at room temperature, resorcinol (2.00 g, 18.2 mmol) was added all at once and dissolved by stirring at 60 ° C. for 2 minutes. 1-Chloro-2-methylpropane (manufactured by Tokyo Chemical Industry, purity 98.0% or more) (1.91 ml, 18.2 mmol) was quickly added dropwise at 60 ° C., followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (10 ml) and 12N hydrochloric acid (2 ml) were added, and the mixture was partitioned into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to give a brown solid (2.12 g). This brown solid was purified by silica gel column chromatography (silica gel 30 g, n-hexane: ethyl acetate = 2: 1) to obtain an ocher solid resorcinol (1.95 g).
比較例２ 直接的アルキル化（２）
水酸化ナトリウム (726 mg, 18.2 mmol) を水 (4 ml) に室温にて溶解後、レゾルシノール (2.00 g, 18.2 mmol) を一括で加え、室温で10分間撹拌して溶解させた。室温にて1-クロロ-2-メチルプロパン (1.91 ml, 18.2 mmol) を素早く滴下後、室温で15時間撹拌した。反応液を室温に冷却後、酢酸エチル (10 ml) および12N 塩酸 (2 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して茶色固体 (2.500 g) を得た。この茶色固体をシリカゲルカラムクマトグラフィー (シリカゲル 30 g, n-ヘキサン：酢酸エチル＝２：１) にて精製を行い、黄土色固体のレゾルシノール (1.93 g) を得た。
Comparative Example 2 Direct alkylation (2)
After sodium hydroxide (726 mg, 18.2 mmol) was dissolved in water (4 ml) at room temperature, resorcinol (2.00 g, 18.2 mmol) was added all at once and dissolved by stirring at room temperature for 10 minutes. 1-Chloro-2-methylpropane (1.91 ml, 18.2 mmol) was quickly added dropwise at room temperature, followed by stirring at room temperature for 15 hours. The reaction mixture was cooled to room temperature, ethyl acetate (10 ml) and 12N hydrochloric acid (2 ml) were added, and the mixture was partitioned into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to give a brown solid (2.500 g). This brown solid was purified by silica gel column chromatography (silica gel 30 g, n-hexane: ethyl acetate = 2: 1) to obtain an ocher solid resorcinol (1.93 g).
比較例１〜２のように、レゾルシノールにアルキルハライドを反応させて直接的に４−アルキルレゾルシノールを得ようと試みたが、反応は進行せず、原料であるレゾルシノールが回収されたに過ぎなかった。 As in Comparative Examples 1 and 2, an attempt was made to obtain 4-alkylresorcinol directly by reacting resorcinol with an alkyl halide, but the reaction did not proceed, and only resorcinol as a raw material was recovered. .
比較例３ 4-（2-メチルアリル）レゾルシノールの製造（１１）
水酸化ナトリウム (3.63 g, 90.8 mmol) を水 (20 ml) に室温にて溶解後、レゾルシノール (10.00 g, 90.8 mmol) を一括で加え、室温で10分間撹拌して溶解させた。室温にてβ-メタリルアルコール（東京化成製、純度98.0%以上） (7.70 ml, 90.8 mmol) を素早く滴下後、60℃で3時間撹拌した。反応液を室温に冷却後、酢酸エチル (50 ml) を加えて有機層と水層（１番目）に分配した。この有機層に2N水酸化ナトリウム (20 ml) を加えて有機層と水層（２番目）に分配した。この操作を１回繰り返した。得られた有機層および水層（１番目〜３番目）を薄層シリカゲルカラムクロマトグラフィーで分析したところ、目的物は確認されず原料であるレゾルシノールのみが確認された。水層（１番目〜３番目）に酢酸エチル (50 ml) および12N 塩酸 (15 ml) を加えて有機層と水層に分配した。この有機層を無水硫酸ナトリウムで乾燥後、濃縮して褐色固体のレゾルシノール (9.87 g) を回収した。
Comparative Example 3 Production of 4- (2-methylallyl) resorcinol (11)
After sodium hydroxide (3.63 g, 90.8 mmol) was dissolved in water (20 ml) at room temperature, resorcinol (10.00 g, 90.8 mmol) was added all at once and dissolved by stirring at room temperature for 10 minutes. Β-methallyl alcohol (manufactured by Tokyo Chemical Industry, purity 98.0% or more) (7.70 ml, 90.8 mmol) was quickly added dropwise at room temperature, followed by stirring at 60 ° C. for 3 hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was partitioned into an organic layer and an aqueous layer (first). 2N sodium hydroxide (20 ml) was added to the organic layer, and the organic layer and the aqueous layer (second) were partitioned. This operation was repeated once. When the obtained organic layer and aqueous layer (first to third) were analyzed by thin layer silica gel column chromatography, the target product was not confirmed, and only resorcinol as a raw material was confirmed. Ethyl acetate (50 ml) and 12N hydrochloric acid (15 ml) were added to the aqueous layer (first to third), and the mixture was partitioned into an organic layer and an aqueous layer. The organic layer was dried over anhydrous sodium sulfate and concentrated to recover brown solid resorcinol (9.87 g).
このように、アルケニルハライドの代わりにアルケニルアルコールを用いた場合には、アルケニル化反応は全く進行せず、原料であるレゾルシノールが回収されたに過ぎなかった。 Thus, when alkenyl alcohol was used instead of alkenyl halide, the alkenylation reaction did not proceed at all, and only resorcinol as a raw material was recovered.
Claims (4)
［式中、Ｒ２は、前記定義と同じである。］ Resorcinol and an alkenyl halide R 2 —X in which the allylic position is substituted with a halogen [R 2 is a C 3-12 optionally substituted with an alkoxyl group having 1 to 12 carbon atoms, a phenyl group, or a heterocyclic ring. A chain, branched or cyclic alkenyl group, X represents halogen. ] And is reacted in the presence of a base in water, 0.5 to 2 times the alkenyl halide used in the range of 2-fold molar equivalent weight less than 0.5 molar equivalents or more with respect to resorcinol, the base is to resorcinol- A method for producing 4-alkenylresorcinol represented by the following general formula (1), wherein a molar equivalent is used and only the base is used as a catalyst .
[Wherein R 2 is the same as defined above. ]
［式中、Ｒ１は、炭素数１〜１２のアルコキシル基、フェニル基、又は複素環で置換されていてもよい炭素数３〜１２の鎖状、分岐又は環状アルキル基を示す。］ The production of 4-alkylresorcinol represented by the following general formula (2), wherein 4-alkenylresorcinol is produced by the method according to claim 1 or 2 , and then the alkenyl group of the 4-alkenylresorcinol is reduced. Method.
[Wherein, R 1 represents a linear, branched or cyclic alkyl group having 3 to 12 carbon atoms which may be substituted with an alkoxyl group having 1 to 12 carbon atoms, a phenyl group, or a heterocyclic ring. ]
4. The method for producing 4-alkylresorcinol according to claim 3 , wherein the reduction of 4-alkenylresorcinol is carried out by catalytic reduction in the presence of a palladium catalyst.
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