JPH03112940A - Production of (+-)-4-formyl-alpha-alkylbenzyl alcohol - Google Patents
Production of (+-)-4-formyl-alpha-alkylbenzyl alcoholInfo
- Publication number
- JPH03112940A JPH03112940A JP24814489A JP24814489A JPH03112940A JP H03112940 A JPH03112940 A JP H03112940A JP 24814489 A JP24814489 A JP 24814489A JP 24814489 A JP24814489 A JP 24814489A JP H03112940 A JPH03112940 A JP H03112940A
- Authority
- JP
- Japan
- Prior art keywords
- formyl
- terephthalaldehyde
- reaction
- formula
- alkylbenzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 16
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 14
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 238000000859 sublimation Methods 0.000 claims description 7
- 230000008022 sublimation Effects 0.000 claims description 7
- 229940079826 hydrogen sulfite Drugs 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 23
- 150000001875 compounds Chemical class 0.000 abstract description 21
- 239000006227 byproduct Substances 0.000 abstract description 12
- 150000004795 grignard reagents Chemical class 0.000 abstract description 8
- 239000007818 Grignard reagent Substances 0.000 abstract description 6
- -1 p-xylene glycols Chemical class 0.000 abstract description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- URLKBWYHVLBVBO-UHFFFAOYSA-N p-dimethylbenzene Natural products CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000007864 aqueous solution Substances 0.000 description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- BWVAOONFBYYRHY-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(CO)C=C1 BWVAOONFBYYRHY-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- KTFKRVMXIVSARW-UHFFFAOYSA-N 4-acetylbenzaldehyde Chemical compound CC(=O)C1=CC=C(C=O)C=C1 KTFKRVMXIVSARW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- ZETCGWYACBNPIH-UHFFFAOYSA-N azane;sulfurous acid Chemical compound N.OS(O)=O ZETCGWYACBNPIH-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 1
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、（±）−４−ホルミル−α−アルキルベンジ
ルアルコール類の工業的に有利な製造方法に関する。
（±）−４−ホルミル−α−アルキルベンジルアルコー
ル類は２種の異なる官能基を１分子中に有し、合成中間
体として有用な化合物である。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an industrially advantageous method for producing (±)-4-formyl-α-alkylbenzyl alcohols.
(±)-4-Formyl-α-alkylbenzyl alcohols have two different functional groups in one molecule and are useful compounds as synthetic intermediates.
（±）−４−ホルミル−α−メチルベンジルアルコール
については、４−ホルミルアセトフェノンのホルミル基
を保護した後、選択的にカルボニル基を還元して得る方
法（Ｃｈｅｍ、Ｌｅｔｔ、 、■、 １６５７６０、
（１９８１）およびＢｕｌｌ、Ｃｈｅｍ、Ｓｏｃ、Ｊｐ
ｎ、＋ ５７＋２４７９−８３、 （１９８４））が知
られている。他にセリウム触媒を用いた二級アルコール
の選択的酸化反応の研究（Ｂｕｌｌ、Ｃｈｅｍ、Ｓｏｃ
、Ｊｐｎ、 ５９１０５−８およびＴｅｔｒａｈｅｄｒ
ｏｎＬｅｔｔ、、２３，５３９−４２． （１９８２）
）の中で、目的反応の副生成物として得られた例がある
。(±)-4-Formyl-α-methylbenzyl alcohol is obtained by protecting the formyl group of 4-formylacetophenone and then selectively reducing the carbonyl group (Chem, Lett, , ■, 165760,
(1981) and Bull, Chem, Soc, Jp.
n, +57+2479-83, (1984)) is known. In addition, research on selective oxidation reactions of secondary alcohols using cerium catalysts (Bull, Chem, Soc.
, Jpn, 59105-8 and Tetrahedr
onLett, 23, 539-42. (1982)
), there are examples where it is obtained as a by-product of the desired reaction.
しかるに、（±）−４−ホルミル−α−アルキルベンジ
ルアルコール類の合成例では、ある種の反応の反応副生
成物として得られたが、あるいはそこで利用された反応
の機構面での研究に興味の中心があるなど純粋に（±）
−４−ホルミル−α−アルキルベンジルアルコール類の
合成ヲ目的としていない。However, in the example of synthesis of (±)-4-formyl-α-alkylbenzyl alcohols, it was obtained as a reaction by-product of a certain type of reaction, or there is interest in researching the mechanism of the reaction used therein. Purely (±) such that there is a center of
The purpose is not to synthesize -4-formyl-α-alkylbenzyl alcohols.
従って、これらの例で用いられた合成法は実際の大量合
成に用いられる方法ではなく、原料の入手も容易ではな
い。本発明者らはく±）−４−ホルミル−α−アルキル
ベンジルアルコール類の合成中間体としての有用性に着
目し、より入手が容易な原料を用いて、（±）−４−ホ
ルミル−α−アルキルベンジルアルコール類を工業的に
有利に製造すべく鋭意検討を重ねた結果、本発明を完成
するに至った。Therefore, the synthesis methods used in these examples are not methods used in actual large-scale synthesis, and the raw materials are not easily available. The present inventors focused on the usefulness of (±)-4-formyl-α-alkylbenzyl alcohols as synthetic intermediates, and developed (±)-4-formyl-α using easily available raw materials. The present invention has been completed as a result of intensive studies aimed at industrially advantageous production of alkylbenzyl alcohols.
すなわち、本発明は、容易に入手可能なテレフタルアル
デヒドに一般式ＲＭｇＸ （式中、Ｒは炭素数１〜９の
飽和もしくは不飽和アルキル基またはアリール基、Ｘは
ハロゲン原子を表す）で示されるグリニヤール試薬を反
応せしめることによって目的化合物を効率よく生成させ
ることができ、この反応における不可避副生成物である
バラキシリレングリコールは目的化合物を亜硫酸水素の
塩とすることによって効率よく分離できることを見出し
てなされたものである。That is, the present invention uses Grignard represented by the general formula RMgX (wherein R represents a saturated or unsaturated alkyl group or aryl group having 1 to 9 carbon atoms, and X represents a halogen atom) to readily available terephthalaldehyde. It was discovered that the target compound can be efficiently produced by reacting reagents, and that the unavoidable byproduct of this reaction, baraxylylene glycol, can be efficiently separated by converting the target compound into a salt of hydrogen sulfite. It is something.
原料のテレフタルアルデヒドは市販品をそのまま用いる
ことができるが、水分を除去すべく減圧乾燥したりある
いは汎用の有機溶剤を用いて再結晶を行う等の操作を行
うのが好ましい。再結晶操作に用いられる有機溶剤とし
ては酢酸エチル、アセトン、クロロホルム、ベンゼン、
ヘキサンなどを例示することができる。Although a commercially available terephthaldehyde as a raw material can be used as it is, it is preferable to perform operations such as drying under reduced pressure to remove moisture or recrystallization using a general-purpose organic solvent. Organic solvents used for recrystallization include ethyl acetate, acetone, chloroform, benzene,
Examples include hexane.
グリニヤール試薬のＲは炭素数１〜９の飽和もしくは不
飽和アルキル基またはアリール基である。R of the Grignard reagent is a saturated or unsaturated alkyl group or an aryl group having 1 to 9 carbon atoms.
アルキル基は好ましくは炭素数が１〜４のものであり、
例としてはメチル基、エチル基等を挙げることができる
。アリール基はフェニル基、トルイル基、アニシル基等
である。Ｘは、ハロゲン原子であり、例えば塩素、臭素
、ヨウ素等である。グリニヤール試薬は対応するハロゲ
ン化アルキルと金属マグネシウムより常法により合成し
て用いてもよいし、ヨウ化メチルマグネシウム、臭化メ
チルマグネシウムなど市販されているグリニヤール試薬
をそのまま用いてもよい。グリニヤール試薬の量は特に
限定するものではないが、テレフタルアルデヒドに対し
０．５〜２倍モル、特に０．８〜１．３倍モル用いるの
が効果的である。The alkyl group preferably has 1 to 4 carbon atoms,
Examples include methyl group, ethyl group, etc. Aryl groups include phenyl, tolyl, anisyl, and the like. X is a halogen atom, such as chlorine, bromine, or iodine. The Grignard reagent may be synthesized by a conventional method from the corresponding alkyl halide and magnesium metal, or commercially available Grignard reagents such as methylmagnesium iodide and methylmagnesium bromide may be used as they are. The amount of the Grignard reagent is not particularly limited, but it is effective to use it in an amount of 0.5 to 2 times, particularly 0.8 to 1.3 times, the amount of terephthalaldehyde.
テレフタルアルデヒドとグリニヤール試薬との反応に用
いられる溶媒としては、たとえばジエチルエーテル、テ
トラヒドロフラン、ヘキサン、トルエン、ベンゼン、ク
ロロベンゼン、ジクロロメタン、ジクロロエタン、四塩
化炭素などのエーテル、脂肪族もしくは芳香族炭化水素
、ハロゲン化炭化水素のごとき反応に不活性な溶媒の、
単独または混合物があげられるが、ジエチルエーテルも
しくはテトラヒドロフラン等のエーテルが好ましく用い
られる。溶媒は予め脱水処理をしておくことが好ましい
。その使用量としては特に制限されない。Solvents used in the reaction of terephthalaldehyde and Grignard reagents include, for example, ethers such as diethyl ether, tetrahydrofuran, hexane, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, carbon tetrachloride, aliphatic or aromatic hydrocarbons, halogenated of reaction-inert solvents such as hydrocarbons,
They may be used alone or in mixtures, but ethers such as diethyl ether or tetrahydrofuran are preferably used. It is preferable that the solvent is dehydrated in advance. The amount used is not particularly limited.
反応を行うにあたっては反応容器を十分に乾燥し、窒素
ガス等の不活性ガスで置換するなどして無酸素雰囲気に
しておく。テレフタルアルデヒドを溶媒に溶解し、所定
の反応温度まで加熱、あるいは冷却する。反応温度につ
いては通常−２０℃から用いる溶媒の還流温度までの範
囲である。反応液を十分に撹拌しつつ予め溶媒に溶解し
たグリニヤール試薬を滴下する。滴下終了後所定時間撹
拌を継続する。この反応を継続させる時間は目的化合物
の収率が高く、かつ副生成物のバラキシリレングリコー
ルの生成率が低くなるように定められ、この時間は予め
試験をして求めておくのがよい。Before carrying out the reaction, the reaction vessel is sufficiently dried and replaced with an inert gas such as nitrogen gas to create an oxygen-free atmosphere. Terephthalaldehyde is dissolved in a solvent and heated or cooled to a predetermined reaction temperature. The reaction temperature is usually in the range from -20°C to the reflux temperature of the solvent used. While thoroughly stirring the reaction solution, a Grignard reagent previously dissolved in a solvent is added dropwise. After the dropwise addition is completed, stirring is continued for a predetermined period of time. The time for which this reaction is continued is determined so that the yield of the target compound is high and the production rate of the by-product baraxylylene glycol is low, and this time is preferably determined by testing in advance.
一般に、滴下終了後３０分以上反応を継続させる必要が
あり、１〜３時間が適当であることが多い。Generally, it is necessary to continue the reaction for 30 minutes or more after the completion of the dropwise addition, and 1 to 3 hours is often appropriate.
所定時間反応を行わせた後、水、好ましくは酸性水溶液
を加えて反応を停止させる。After the reaction is allowed to proceed for a predetermined period of time, water, preferably an acidic aqueous solution, is added to stop the reaction.
反応物は溶媒層と水層よりなり、溶媒層には目的化合物
のほかに原料のテレフタルアルデヒド及びその両方のア
ルデヒド基が還元されてＲ基が結合した副生成物のバラ
キシリレングリコールが含まれている。そこで、反応物
から目的化合物を分解する工程においてはまず溶媒層と
水層を分ける。The reactant consists of a solvent layer and an aqueous layer, and the solvent layer contains, in addition to the target compound, the raw material terephthalaldehyde and the by-product baraxylylene glycol in which the aldehyde groups of both are reduced and R groups are bonded. There is. Therefore, in the step of decomposing a target compound from a reactant, first a solvent layer and an aqueous layer are separated.
目的化合物の収率を高めるために必要により水層から目
的化合物を有機溶媒により抽出する。抽出溶媒としては
ジエチルエーテル、ベンゼン、クロロホルム、酢酸エチ
ル、ジクロロメタン等の水と混和しないものがあげられ
る。In order to increase the yield of the target compound, if necessary, the target compound is extracted from the aqueous layer using an organic solvent. Extraction solvents include those that are immiscible with water, such as diethyl ether, benzene, chloroform, ethyl acetate, and dichloromethane.
目的化合物からバラキシリレングリコールの分離は目的
化合物を亜硫酸水素の塩とすることによって行うことが
できる。目的化合物を亜硫酸水素塩とし、バラキシリレ
ングリコールと分離するためには、目的化合物を含む溶
液に亜硫酸水素塩を加えて水抽出を行えばよい。この亜
硫酸水素塩としては亜硫酸水素ナトリウムが好ましいが
、亜硫酸水素カリウム、亜硫酸水素アンモニウム等目的
化合物の塩を形成しうるちのであれば如何なる塩であっ
てもよい。亜硫酸水素塩は通常水溶液の形で加える。亜
硫酸水素塩の水溶液の濃度としては通常２０〜３０重量
％の範囲である。水溶液中の亜硫酸水素塩の重量は、目
的化合物、副生成物のバラキシリレングリコール及び原
料のテレフタルアルヒトよりなる反応混合物の重量の２
倍以上の量があればよいが、４〜６倍重量の範囲が好ま
しい。Barraxylylene glycol can be separated from the target compound by converting the target compound into a salt of hydrogen sulfite. In order to convert the target compound into a hydrogen sulfite salt and separate it from baraxylylene glycol, the hydrogen sulfite salt may be added to a solution containing the target compound, followed by water extraction. The hydrogen sulfite is preferably sodium hydrogen sulfite, but any salt may be used as long as it can form a salt of the target compound, such as potassium hydrogen sulfite or ammonium hydrogen sulfite. Bisulfite is usually added in the form of an aqueous solution. The concentration of the aqueous solution of bisulfite is usually in the range of 20 to 30% by weight. The weight of the bisulfite in the aqueous solution is 2 times the weight of the reaction mixture consisting of the target compound, the by-product baraxylylene glycol, and the raw material terephthalate.
The amount should be at least double the weight, but a range of 4 to 6 times the weight is preferred.
亜硫酸水素塩の水溶液は反応復水層を分離した溶媒層に
直接加えてもよいが、反応混合物を亜硫酸水素塩の水溶
液と十分に混和し、目的化合物の塩形成速度を早めるた
めに一旦溶媒層を乾固し、しかる後に亜硫酸水素塩の水
溶液を加えるのが好ましい。乾固して得られた反応混合
物を亜硫酸水素塩の水溶液と十分に混和する。混和の効
率を上げるため、反応混合物を少量のエタノール、メタ
ノールなどの水溶性の有機溶媒で希釈してもよい。The aqueous solution of bisulfite may be added directly to the solvent layer from which the reaction condensate layer has been separated, but in order to thoroughly mix the reaction mixture with the aqueous solution of bisulfite and accelerate the rate of salt formation of the target compound, add the aqueous solution to the solvent layer once. It is preferred to dry it and then add an aqueous solution of bisulfite. The reaction mixture obtained by drying is thoroughly mixed with an aqueous solution of bisulfite. To increase the efficiency of mixing, the reaction mixture may be diluted with a small amount of a water-soluble organic solvent such as ethanol or methanol.
この場合、混和後、減圧下で希釈に用いた有機溶媒を除
去する必要がある。反応混合物と亜硫酸水素塩の水溶液
との混和物に水と混和しない有機溶媒を加えて副生成物
のバラキシリレングリコールを抽出除去する。この有機
溶媒はジエチルエーテル、ベンゼン、クロロホルム、酢
酸エチル、ジクロロメタン等を用いることができる。こ
の副生成物を除去する工程においては原料のテレフタル
アルデヒドも水溶性の亜硫酸水素塩となって目的化合物
とともに水溶液中に残る。In this case, after mixing, it is necessary to remove the organic solvent used for dilution under reduced pressure. A water-immiscible organic solvent is added to a mixture of the reaction mixture and an aqueous solution of bisulfite to extract and remove the by-product baraxylylene glycol. As this organic solvent, diethyl ether, benzene, chloroform, ethyl acetate, dichloromethane, etc. can be used. In the step of removing this by-product, the raw material terephthalaldehyde also becomes a water-soluble bisulfite and remains in the aqueous solution together with the target compound.
そこで、次に目的化合物から原料のテレフタルアルデヒ
ドを分離する。この副生成物を除去した亜硫酸水素ナト
リウム水溶液中の（±）−４−ホルミル−α−アルキル
ベンジルアルコール及び未反応のテレフタルアルデヒド
の塩は、アルカリを用いて塩基性にすることにより容易
に分解し、油状物質あるいは固体として析出する。ここ
で用いられるアルカリとしては炭酸ナトリウム、炭酸水
素ナトリウム、水酸化ナトリウム、水酸化カリウム等を
例示することができる。油状物質あるいは固体として析
出した（±）−４−ホルミル−α−アルキルベンジルア
ルコール及び未反応のテレフタルアルデヒドは抽出ある
いは濾過により回収することができる。未反応のテレフ
タルアルデヒドを含む（±）−４−ホルミル−α−アル
キルベンジルアルコールは昇華によりテレフタルアルデ
ヒドを除去することにより、純粋な（±）−４−ホルミ
ル−α−アルキルベンジルアルコールとすることができ
る。昇華は減圧度３０ ｎｎｎ Ｈｇ以下、温度は７０
〜１００°Ｃの範囲で行うのが好ましい。なお、このテ
レフタルアルデヒドの昇華による除去はテレフタリルア
ルコールの除去工程に先立って行ってもよいことはいう
までもない。Therefore, next, the raw material terephthalaldehyde is separated from the target compound. The (±)-4-formyl-α-alkylbenzyl alcohol and unreacted terephthalaldehyde salt in the aqueous sodium bisulfite solution from which this byproduct has been removed can be easily decomposed by making it basic using an alkali. , precipitates as an oil or solid. Examples of the alkali used here include sodium carbonate, sodium hydrogen carbonate, sodium hydroxide, potassium hydroxide, and the like. (±)-4-Formyl-α-alkylbenzyl alcohol and unreacted terephthalaldehyde precipitated as an oil or solid can be recovered by extraction or filtration. (±)-4-formyl-α-alkylbenzyl alcohol containing unreacted terephthalaldehyde can be converted into pure (±)-4-formyl-α-alkylbenzyl alcohol by removing terephthalaldehyde by sublimation. can. Sublimation is at a reduced pressure of 30 nnn Hg or less and a temperature of 70
It is preferable to carry out in the range of -100 degreeC. It goes without saying that this removal of terephthalaldehyde by sublimation may be performed prior to the step of removing terephthalyl alcohol.
本発明の製造方法における反応式を次に示す。 The reaction formula in the production method of the present invention is shown below.
また、テレフタリルアルコールの分離工程においては、
反応混合物の（±）−４−ホルミル−αα−アルキルベ
ンジルアルコール及び未反応のテレフタルアルデヒドは
、分子中のホルミル基と亜硫酸水素イオンが水溶性の塩
を形成することにより、水溶液に完全に溶解し、ホルミ
ル基を有さない副生成物は、油状物質あるいは固体とし
て溶は残る。In addition, in the separation process of terephthalyl alcohol,
(±)-4-Formyl-αα-alkylbenzyl alcohol and unreacted terephthalaldehyde in the reaction mixture are completely dissolved in the aqueous solution because the formyl group and hydrogen sulfite ion in the molecule form a water-soluble salt. By-products that do not have formyl groups remain in solution as oily substances or solids.
テレフタルアルデヒドの分離工程においてはテレフタル
アルデヒドが昇華性を有し、一方（±）４−ホルミル−
α−アルキルベンジルアルコールは昇華性を有しないと
ころからテレフタルアルデヒドを選択的に昇華させて分
離除去している。In the separation process of terephthalaldehyde, terephthalaldehyde has sublimation property, while (±)4-formyl-
α-Alkylbenzyl alcohol does not have sublimation properties, so terephthalaldehyde is selectively sublimed and separated and removed.
実施例１〜１４
滴下漏斗、還流冷却器をつけたフラスコを十分乾燥し、
反応容器内を窒素置換した。市販品を酢酸エチルにより
再結晶し、さらに減圧乾燥したテレフタルアルデヒド１
．３４ｇと無水ジエチルエーテル２００−を入れ、撹拌
し、完全に溶解した。市販の０．９７ ｍｏｌ／ｌヨウ
化メチルマメチルマグネシウムジエチルエーテル溶液１
２３０分かけて滴下した。滴下終了後１時間室温で撹拌
を継続し、飽和塩化アンモニウム水溶液５０−を加え、
反応を停止させた。Examples 1 to 14 Thoroughly dry a flask equipped with a dropping funnel and a reflux condenser,
The inside of the reaction vessel was replaced with nitrogen. Terephthalaldehyde 1 obtained by recrystallizing a commercially available product from ethyl acetate and drying it under reduced pressure.
．． 34 g and 200 g of anhydrous diethyl ether were added and stirred to completely dissolve. Commercially available 0.97 mol/l methylmamethyliodide diethyl ether solution 1
The mixture was added dropwise over 230 minutes. After the dropwise addition was completed, stirring was continued at room temperature for 1 hour, and 50% of a saturated ammonium chloride aqueous solution was added.
The reaction was stopped.
エーテル層と水層を分離し、分離した水層から１回あた
り５０ｄのジエチルエーテルで３回抽出した。The ether and aqueous layers were separated, and the separated aqueous layer was extracted three times with 50 d of diethyl ether each time.
抽出液は３０ｇの硫酸ナトリウムで乾燥後、濃縮乾固し
た。得られた反応混合物は３０ｄのエタノールで希釈し
、３０％亜硫酸水素ナトリウム水溶液３０ｇとよく混和
した。希釈用のエタノールは減圧後除去し、再び水溶液
とした後、水溶液中の副生成物を１回あたり５０成のジ
エチルエーテルで３回抽出することで除去した。水溶液
に炭酸ナトリウムをＬｏｇ入れ、水溶液から１回あたり
５０戚のジエチルエーテルで３回抽出した。抽出液を乾
燥後、濃縮し、そのまま３０ｍｍＨｇ、８０℃で５時間
保持し、昇華により未反応のテレフタルアルデヒドを除
去し、（±）−４−ホルミル−α−メチルベンジルアル
コールを０．８ｇ得た。The extract was dried over 30 g of sodium sulfate and then concentrated to dryness. The resulting reaction mixture was diluted with 30 d of ethanol and mixed well with 30 g of 30% aqueous sodium bisulfite solution. Ethanol for dilution was removed after reducing the pressure, and after the solution was made into an aqueous solution again, the by-products in the aqueous solution were removed by extraction three times with 50 ml of diethyl ether each time. A log of sodium carbonate was added to the aqueous solution, and the aqueous solution was extracted three times with 50% diethyl ether each time. After drying the extract, it was concentrated and kept as it was at 30 mmHg and 80°C for 5 hours, and unreacted terephthalaldehyde was removed by sublimation to obtain 0.8 g of (±)-4-formyl-α-methylbenzyl alcohol. .
表１に記載したほかは上記と同様にして上記も含めて合
計１４回（±）−４−ホルミル−α−メチルベンジルア
ルコールの合成を行った。得られた結果を表１にまとめ
て示す。なお、各生成物の同定は９０ＭＨ２’Ｈ−ＮＭ
Ｒで行った。実験Ｎα１１と１３は不均一系での合成例
であり、他はすべて均−系での合成例である。Except as described in Table 1, synthesis of (±)-4-formyl-α-methylbenzyl alcohol was carried out in the same manner as above for a total of 14 times including the above. The obtained results are summarized in Table 1. In addition, the identification of each product is 90MH2'H-NM
I went with R. Experiments Nα11 and 13 are examples of synthesis in a heterogeneous system, and all others are examples of synthesis in a homogeneous system.
かくして、本発明の方法によれば、入手容易な原料を出
発物質として、簡便な扱作により工業的に有利に、各種
合成中間体どして有用な（±）−４−ホルミル−α−ア
ルキルベンジルアルコール類を得ることができる。Thus, according to the method of the present invention, (±)-4-formyl-α-alkyl, which is useful as various synthetic intermediates, can be produced industrially with easy handling using easily available raw materials as starting materials. Benzyl alcohols can be obtained.
Claims (3)
Ｒは炭素数１〜９の飽和もしくは不飽和アルキル基また
はアリール基、Ｘはハロゲン原子を表す）で示されるグ
リニャール試薬を反応させることを特徴とする一般式、 ▲数式、化学式、表等があります▼ （式中、Ｒは前記と同じ意味である。） で示される（±）−４−ホルミル−α−アルキルベンジ
ルアルコール類の製造方法(1) Terephthalaldehyde has the general formula RMgX (wherein,
R is a saturated or unsaturated alkyl group or aryl group having 1 to 9 carbon atoms, and X is a halogen atom. ▼ (In the formula, R has the same meaning as above.) Method for producing (±)-4-formyl-α-alkylbenzyl alcohols
４−ホルミル−α−アルキルベンジルアルコール類及び
一般式 ▲数式、化学式、表等があります▼ （式中、Ｒは前記と同じ意味である。） で示されるパラキシリレングリコールを含む混合物に亜
硫酸水素塩を加えて有機溶媒層−水層間で抽出を行うこ
とを特徴とする（±）−４−ホルミル−α−アルキルベ
ンジルアルコール類の製造方法(2) (±)- represented by the general formula in claim (1)
Hydrogen sulfite is added to a mixture containing paraxylylene glycol represented by 4-formyl-α-alkylbenzyl alcohols and the general formula ▲Mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R has the same meaning as above.) A method for producing (±)-4-formyl-α-alkylbenzyl alcohols, which comprises adding a salt and performing extraction between an organic solvent layer and an aqueous layer.
４−ホルミル−α−アルキルベンジルアルコール類及び
テレフタルアルデヒドを含む混合物からテレフタルアル
デヒドを昇華させて回収することを特徴とする（±）−
４−ホルミル−α−アルキルベンジルアルコール類の製
造方法(3) (±)− represented by the general formula in claim (1)
(±)- characterized in that terephthalaldehyde is recovered by sublimation from a mixture containing 4-formyl-α-alkylbenzyl alcohol and terephthalaldehyde.
Method for producing 4-formyl-α-alkylbenzyl alcohols
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24814489A JPH03112940A (en) | 1989-09-26 | 1989-09-26 | Production of (+-)-4-formyl-alpha-alkylbenzyl alcohol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24814489A JPH03112940A (en) | 1989-09-26 | 1989-09-26 | Production of (+-)-4-formyl-alpha-alkylbenzyl alcohol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03112940A true JPH03112940A (en) | 1991-05-14 |
Family
ID=17173880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24814489A Pending JPH03112940A (en) | 1989-09-26 | 1989-09-26 | Production of (+-)-4-formyl-alpha-alkylbenzyl alcohol |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03112940A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0850225A1 (en) * | 1994-05-20 | 1998-07-01 | Smithkline Beecham Corporation | Intermediate for preparing a pharmaceutically active compound |
| JP2006045224A (en) * | 2004-07-30 | 2006-02-16 | Xerox Corp | Method for producing formylated arylamine |
| KR100897335B1 (en) * | 2006-04-18 | 2009-05-15 | 주식회사 엘지화학 | A purification method of aromatic dialdehyde, and a purification apparatus for the same |
| JP2010510205A (en) * | 2006-11-16 | 2010-04-02 | エルジー・ケム・リミテッド | Method for purifying terephthalaldehyde |
-
1989
- 1989-09-26 JP JP24814489A patent/JPH03112940A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0850225A1 (en) * | 1994-05-20 | 1998-07-01 | Smithkline Beecham Corporation | Intermediate for preparing a pharmaceutically active compound |
| EP0850225A4 (en) * | 1994-05-20 | 1998-07-01 | ||
| JP2006045224A (en) * | 2004-07-30 | 2006-02-16 | Xerox Corp | Method for producing formylated arylamine |
| KR100897335B1 (en) * | 2006-04-18 | 2009-05-15 | 주식회사 엘지화학 | A purification method of aromatic dialdehyde, and a purification apparatus for the same |
| JP2010510205A (en) * | 2006-11-16 | 2010-04-02 | エルジー・ケム・リミテッド | Method for purifying terephthalaldehyde |
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