JPH0128731B2 - - Google Patents
Info
- Publication number
- JPH0128731B2 JPH0128731B2 JP56032542A JP3254281A JPH0128731B2 JP H0128731 B2 JPH0128731 B2 JP H0128731B2 JP 56032542 A JP56032542 A JP 56032542A JP 3254281 A JP3254281 A JP 3254281A JP H0128731 B2 JPH0128731 B2 JP H0128731B2
- Authority
- JP
- Japan
- Prior art keywords
- product
- cyclohexadienone
- selectivity
- yield
- cyclodextrin
- 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.)
- Expired
Links
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 229920000858 Cyclodextrin Polymers 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- WGHKKEJHRMUKDK-UHFFFAOYSA-N cyclohexa-2,5-dien-1-one Chemical class O=C1C=CCC=C1 WGHKKEJHRMUKDK-UHFFFAOYSA-N 0.000 claims description 12
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 150000002989 phenols Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000047 product Substances 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 10
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- 229930003836 cresol Natural products 0.000 description 8
- FDQQNNZKEJIHMS-UHFFFAOYSA-N 3,4,5-trimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1C FDQQNNZKEJIHMS-UHFFFAOYSA-N 0.000 description 4
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- NAUBSKHQFFCEMQ-UHFFFAOYSA-N 2-hydroxy-5-phenylbenzaldehyde Chemical compound C1=C(C=O)C(O)=CC=C1C1=CC=CC=C1 NAUBSKHQFFCEMQ-UHFFFAOYSA-N 0.000 description 2
- JLYNSZBVOSPNMJ-UHFFFAOYSA-N 4-(dichloromethyl)-3,4,5-trimethylcyclohexa-2,5-dien-1-one Chemical compound CC1=CC(=O)C=C(C)C1(C)C(Cl)Cl JLYNSZBVOSPNMJ-UHFFFAOYSA-N 0.000 description 2
- MJRRCEHODULPAV-UHFFFAOYSA-N 4-(dichloromethyl)-4-methylcyclohexa-2,5-dien-1-one Chemical compound ClC(Cl)C1(C)C=CC(=O)C=C1 MJRRCEHODULPAV-UHFFFAOYSA-N 0.000 description 2
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 2
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- -1 cyclic oligosaccharide Chemical class 0.000 description 2
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical compound O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- BPRYUXCVCCNUFE-UHFFFAOYSA-N 2,4,6-trimethylphenol Chemical compound CC1=CC(C)=C(O)C(C)=C1 BPRYUXCVCCNUFE-UHFFFAOYSA-N 0.000 description 1
- SROIDXDTTVPRNA-UHFFFAOYSA-N 4-(dichloromethyl)-2,4,6-trimethylcyclohexa-2,5-dien-1-one Chemical compound CC1=CC(C)(C(Cl)Cl)C=C(C)C1=O SROIDXDTTVPRNA-UHFFFAOYSA-N 0.000 description 1
- IBERXRAOEININY-UHFFFAOYSA-N 4-(dichloromethyl)-4-methoxycyclohexa-2,5-dien-1-one Chemical group COC1(C(Cl)Cl)C=CC(=O)C=C1 IBERXRAOEININY-UHFFFAOYSA-N 0.000 description 1
- YRUDVWYZNVZIJI-UHFFFAOYSA-N 4-(dichloromethyl)-4-phenylcyclohexa-2,5-dien-1-one Chemical compound C=1C=CC=CC=1C1(C(Cl)Cl)C=CC(=O)C=C1 YRUDVWYZNVZIJI-UHFFFAOYSA-N 0.000 description 1
- FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 1
- GEOWCLRLLWTHDN-UHFFFAOYSA-N Formyl-Phenol Natural products O=COC1=CC=CC=C1 GEOWCLRLLWTHDN-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000006371 dihalo methyl group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は４位にジハロメチル基を有する２，５
−シクロヘキサジエノン誘導体〔〕
The present invention provides 2,5
-Cyclohexadienone derivative []
【式】
（式中、Ｘはハロゲン、Ａ、Ｂ、Ｃ、Ｄ、Ｅは水
素、置換および非置換アルキル基、アリル基、ア
ルコキシル基またはアリール基を示す。なお、Ａ
は水素をとることはない。）を選択的に製造する
方法に関する。
２，５−シクロヘキサジエノン誘導体は２個の
Ｃ−Ｃ二重結合とカルボニル基とが共役している
ために反応性に富み、生理活性物質をその他の有
用物質の合成原料となる重要な化合物である。ま
た、２，５−シクロヘキサジエノン誘導体のうち
には、それ自身、生理活性を示すものも多い。
これまでに、ハロホルム、水酸化ナトリウムま
たは水酸化カリウムとパラ位置置換フエノールと
により４−ジハロメチル−２，５−シクロヘキサ
ジエノン誘導体を合成する方法はReimer−
Tiemann反応として知られ公知であつた。
しかしながら、後述の比較例に見られるよう
に、上記の反応の主たる生成物は、置換基Ｃまた
はＤが水素のときには水酸基に対してオルト位が
ホルミル化された化合物〔２〕であり、またＣお
よびＤの両方が水素以外のときには２位にジハロ
メチル基が導入された化合物〔３〕である。その
ために、従来の方法における２，５−シクロヘキ
サジエノン誘導体〔１〕の収率は５〜10％と低
く、２，５−シクロヘキサジエノン誘導体を得る
のに大量の原料が必要であると同時に複雑な分離
操作を必要とした。[Formula] (wherein,
never takes up hydrogen. ). 2,5-Cyclohexadienone derivatives are highly reactive because two C-C double bonds are conjugated with a carbonyl group, and are important compounds that serve as raw materials for the synthesis of physiologically active substances and other useful substances. It is. Furthermore, many of the 2,5-cyclohexadienone derivatives themselves exhibit physiological activity. Until now, a method for synthesizing 4-dihalomethyl-2,5-cyclohexadienone derivatives using haloform, sodium hydroxide or potassium hydroxide and a para-substituted phenol has been proposed by Reimer-
It was known as the Tiemann reaction. However, as seen in the comparative example below, the main product of the above reaction is a compound [2] in which the ortho position to the hydroxyl group is formylated when the substituent C or D is hydrogen; When both of and D are other than hydrogen, it is a compound [3] in which a dihalomethyl group is introduced at the 2-position. Therefore, the yield of 2,5-cyclohexadienone derivative [1] in the conventional method is as low as 5-10%, and a large amount of raw material is required to obtain the 2,5-cyclohexadienone derivative. Required complicated separation operations.
【式】【formula】
【式】
本発明は、上記の反応系に環状オリゴ糖である
シクロデキストリンを添加することにより、目的
生成物である２，５−シクロヘキサジエノン誘導
体〔１〕の収率および選択性を顕著に向上させ、
省原料と分離操作の簡素化を実現したものであ
る。
すなわち本発明者らは、パラ位置置換フエノー
ル誘導体と水酸化ナトリウムまたは水酸化カリウ
ムの水溶液にシクロデキストリンを加え、溶解せ
しめた後にハロホルムを徐々に滴下することによ
り、２，５−シクロヘキサジエノン誘導体を高収
率、高選択性で合成することに成功した。本発明
における２，５−シクロヘキサジエノン誘導体の
生成の選択率は90〜100％と高く、オルト位反応
物〔２〕または〔３〕の副生を生成物全体に対し
て10％以下におさえることができた。このような
選択性の向上により、抽出あるいは蒸留のように
極めて簡便な分離操作により、目的生成物を30〜
90％という高収率で得ることに成功した。
シクロデキストリンとしては、α−シクロデキ
ストリンとβ−シクロデキストリンのいずれも用
いることができる。シクロデキストリンの添加量
としては、ほぼ100％に近い選択率で２，５−シ
クロヘキサジエノン誘導体を得るためには、パラ
位置換フエノール誘導体に対するモル比で0.4以
上が望ましいが、これ以下の量のシクロデキスト
リン使用量でも２，５−シクロヘキサジエノン誘
導体の生成の選択性の向上は達成される。
シクロデキストリンは反応中に変化せず、反応
後そのまま再使用が可能である。クロロホルム抽
出により２，５−シクロヘキサジエノン誘導体を
分離後、反応系を酸性にすると溶解度の減少のた
めにシクロデキストリンが沈澱する。この簡便な
方法でシクロデキストリンの７〜８割は回収さ
れ、回収されたシクロデキストリンは完全に再使
用にたえる。
つぎに本発明を具体的に実施例をあげて説明す
るが、これにより本発明を制限するものではな
い。
実施例 １
１ｇのＰ−クレゾールと８ｇのβ−シクロデキ
ストリンを50mlの10％水酸化ナトリウム水溶液に
溶かし、75℃において５mlのクロロホルムを徐々
に滴下し、10時間反応せしめる。反応後、反応液
を50mlのクロロホルムで５回抽出し、クロロホル
ム層を乾燥した。このようにして、0.75ｇの生成
物を得、 1H−NMR測定により、この生成物は
すべて４−ジクロロメチル−４−メチル−２，５
−シクロヘキサジエノンであることがわかつた。
すなわち、目的物の収率は75％であり、選択率は
100％であつた。
実施例 ２
実施例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇの４−フエニルフエノ
ールを使用し、0.89ｇの生成物を得た。 1H−
NMR測定により、この生成物の95％は４−ジク
ロロメチル−４−フエニル−２，５−シクロヘキ
サジエノンであり、残りは２−ホルミル−４−フ
エニルフエノールであつた。すなわち、、目的物
の収率は85％であり、選択率は95％であつた。
実施例 ３
実施例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇの３，４，５−トリメ
チルフエノールを使用し、0.90ｇの生成物を得
た。この生成物はすべて３，４，５−トリメチル
−４−ジクロロメチル−２，５−シクロヘキサジ
エノンであつた。すなわち、目的物の収率は90％
であり、選択率は100％であつた。
実施例 ４
実施例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇのar−２−テトラヒド
ロナフトールを使用し、0.56ｇの９−ジクロロメ
チル−６−オキソ−１，２，３，４，６，９−ヘ
キサヒドロナフタレンを得た。すなわち、目的物
の収率は56％であり、選択率は100％であつた。
実施例 ５
実施例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇの２，４，６−トリメ
チルフエノールを使用し、0.75ｇの２，４，６−
トリメチル−４−ジクロロメチル−２，５−シク
ロヘキサジエノンを得た。すなわち、目的物の収
率は75％であり、選択率は100％であつた。
実施例 ６
実施例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇのＰ−メトキシフエノ
ールを使用し、0.31ｇの生成物を得た。この生成
物の96％は４−ジクロロメチル−４−メトキシ−
２，５−シクロヘキサジエノンであり、４％が２
−ホルミル−４−メトキシフエノールであつた。
すなわち、目的物の収率は30％であり、選択率は
96％であつた。
実施例 ７
実施例４と同様の実験操作により、８ｇのβ−
シクロデキストリンの代わりに８ｇのα−シクロ
デキストリンを使用し、１ｇのar−２−テトラヒ
ドロナフトールより0.41ｇの生成物を得た。生成
物の93％は９−ジクロロメチル−６−オキソ−
１，２，３，４，６，９−ヘキサヒドロナフタレ
ンであつた。すなわち、目的物の収率は38％であ
り、選択率は93％であつた。
実施例 ８
実施例１と同様の実験操作により、10％水酸化
ナトリウム水溶液の代わりに10％水酸化カリウム
水溶液を使用し、１ｇのＰ−クレゾールより0.52
ｇの４−ジクロロメチル−４−メチル−２，５−
シクロヘキサジエノンを得た。すなわち、目的物
の収率は52％であり、選択率は100％であつた。
比較例 １
１ｇのＰ−クレゾールを50mlの10％水酸化ナト
リウム水溶液に溶かし、75℃において５mlのクロ
ロホルムを徐々に滴下し、10時間反応せしめる。
反応後、反応液を50mlのクロロホルムで５回抽出
し、クロロホルム層を乾燥した。このようにし
て、0.29ｇの生成物を得た。生成物の28％が４−
ジクロロメチル−４−メチル−２，５−シクロヘ
キサジエノンであり、72％は２−ホルミル−４−
メチルフエノールであつた。すなわち、目的物の
収率は８％であり、選択率は28％であつた。
比較例 ２
比較例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇの４−フエニルフエノ
ールを使用し、0.50ｇの生成物を得た。生成物の
12％が４−ジクロロメチル−４−フエニル−２，
５−シクロヘキサジエノンであり、88％は２−ホ
ルミル−４−フエニルフエノールであつた。すな
わち、目的物の収率は６％であり、選択率は12％
であつた。
比較例 ３
比較例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇの３，４，５−トリメ
チルフエノールを使用し、0.38ｇの生成物を得
た。生成物の５％が３，４，５−トリメチル−４
−ジクロロメチル−２，５−シクロヘキサジエノ
ンであり、95％は３，４，５−トリメチル−２−
ホルミルフエノールであつた。すなわち、目的物
の収率は５％であり、選択率は13％であつた。
比較例 ４
比較例１と同様の実験操作により、１ｇのＰ−
クレゾールの代わりに１ｇのar−２−テトラヒド
ロナフトールを使用し、0.52ｇの生成物を得た。
生成物の19％が９−ジクロロメチル−６−オキソ
−１，２，３，４，６，９−ヘキサヒドロナフタ
レンであり、81％は１−ホルミル−ar−２−テト
ラヒドロナフトールであつた。すなわち、目的物
の収率は10％であり、選択率は19％であつた。
比較例 ５
実施例１と同様の操作を、クロロホルムを徐々
に滴下する代わりに、クロロホルムを反応初期に
一度に添加して行つた。その結果、４−ジクロロ
メチル−４−メチル−２，５−シクロヘキサジエ
ンの収率は56％であり、選択率は78％であつた。[Formula] The present invention significantly improves the yield and selectivity of the desired product, 2,5-cyclohexadienone derivative [1], by adding cyclodextrin, which is a cyclic oligosaccharide, to the above reaction system. improve,
This saves raw materials and simplifies separation operations. That is, the present inventors added cyclodextrin to an aqueous solution of a para-substituted phenol derivative and sodium hydroxide or potassium hydroxide, dissolved it, and then slowly added haloform dropwise to obtain a 2,5-cyclohexadienone derivative. We succeeded in synthesizing it with high yield and high selectivity. The selectivity for the production of 2,5-cyclohexadienone derivatives in the present invention is as high as 90 to 100%, and the by-product of the ortho-position reactant [2] or [3] is suppressed to less than 10% of the total product. I was able to do that. With this improved selectivity, the desired product can be isolated from 30 to 30% using extremely simple separation operations such as extraction or distillation.
We succeeded in obtaining it with a high yield of 90%. As the cyclodextrin, both α-cyclodextrin and β-cyclodextrin can be used. In order to obtain a 2,5-cyclohexadienone derivative with a selectivity close to 100%, the amount of cyclodextrin added is preferably 0.4 or more in molar ratio to the para-substituted phenol derivative; Even with the amount of cyclodextrin used, improved selectivity in the production of 2,5-cyclohexadienone derivatives can be achieved. Cyclodextrin does not change during the reaction and can be reused as is after the reaction. After separating the 2,5-cyclohexadienone derivative by chloroform extraction, when the reaction system is made acidic, cyclodextrin precipitates due to decreased solubility. With this simple method, 70 to 80% of the cyclodextrin can be recovered, and the recovered cyclodextrin can be completely reused. Next, the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto. Example 1 1 g of P-cresol and 8 g of β-cyclodextrin are dissolved in 50 ml of 10% aqueous sodium hydroxide solution, and 5 ml of chloroform is gradually added dropwise at 75° C. to react for 10 hours. After the reaction, the reaction solution was extracted five times with 50 ml of chloroform, and the chloroform layer was dried. In this way, 0.75 g of product was obtained, which according to 1 H-NMR measurement was entirely 4-dichloromethyl-4-methyl-2,5
- It turned out to be cyclohexadienone.
That is, the yield of the target product is 75%, and the selectivity is
It was 100%. Example 2 Through the same experimental procedure as in Example 1, 1 g of P-
1 g of 4-phenylphenol was used instead of cresol, yielding 0.89 g of product. 1 H−
According to NMR measurements, 95% of the product was 4-dichloromethyl-4-phenyl-2,5-cyclohexadienone, and the remainder was 2-formyl-4-phenylphenol. That is, the yield of the target product was 85% and the selectivity was 95%. Example 3 Through the same experimental procedure as in Example 1, 1 g of P-
1 g of 3,4,5-trimethylphenol was used instead of cresol, yielding 0.90 g of product. The product was all 3,4,5-trimethyl-4-dichloromethyl-2,5-cyclohexadienone. In other words, the yield of the target product is 90%
The selectivity was 100%. Example 4 Through the same experimental procedure as in Example 1, 1 g of P-
Using 1 g of ar-2-tetrahydronaphthol instead of cresol, 0.56 g of 9-dichloromethyl-6-oxo-1,2,3,4,6,9-hexahydronaphthalene was obtained. That is, the yield of the target product was 56%, and the selectivity was 100%. Example 5 Through the same experimental procedure as in Example 1, 1 g of P-
Use 1 g of 2,4,6-trimethylphenol instead of cresol and 0.75 g of 2,4,6-
Trimethyl-4-dichloromethyl-2,5-cyclohexadienone was obtained. That is, the yield of the target product was 75% and the selectivity was 100%. Example 6 Through the same experimental procedure as in Example 1, 1 g of P-
1 g of P-methoxyphenol was used instead of cresol, yielding 0.31 g of product. 96% of this product is 4-dichloromethyl-4-methoxy-
2,5-cyclohexadienone, 4% of which is 2
-formyl-4-methoxyphenol.
That is, the yield of the target product is 30%, and the selectivity is
It was 96%. Example 7 Through the same experimental procedure as in Example 4, 8 g of β-
8 g of α-cyclodextrin was used instead of cyclodextrin, and 0.41 g of product was obtained from 1 g of ar-2-tetrahydronaphthol. 93% of the product is 9-dichloromethyl-6-oxo-
It was 1,2,3,4,6,9-hexahydronaphthalene. That is, the yield of the target product was 38% and the selectivity was 93%. Example 8 By the same experimental procedure as in Example 1, using 10% potassium hydroxide aqueous solution instead of 10% sodium hydroxide aqueous solution, 0.52
g of 4-dichloromethyl-4-methyl-2,5-
Cyclohexadienone was obtained. That is, the yield of the target product was 52% and the selectivity was 100%. Comparative Example 1 1 g of P-cresol was dissolved in 50 ml of 10% aqueous sodium hydroxide solution, and 5 ml of chloroform was gradually added dropwise at 75° C. to react for 10 hours.
After the reaction, the reaction solution was extracted five times with 50 ml of chloroform, and the chloroform layer was dried. In this way, 0.29 g of product was obtained. 28% of the product is 4-
Dichloromethyl-4-methyl-2,5-cyclohexadienone, 72% 2-formyl-4-
It was methylphenol. That is, the yield of the target product was 8% and the selectivity was 28%. Comparative Example 2 By the same experimental procedure as in Comparative Example 1, 1 g of P-
1 g of 4-phenylphenol was used instead of cresol, yielding 0.50 g of product. of the product
12% is 4-dichloromethyl-4-phenyl-2,
It was 5-cyclohexadienone and 88% was 2-formyl-4-phenylphenol. In other words, the yield of the target product is 6%, and the selectivity is 12%.
It was hot. Comparative Example 3 Through the same experimental procedure as in Comparative Example 1, 1 g of P-
1 g of 3,4,5-trimethylphenol was used instead of cresol, yielding 0.38 g of product. 5% of the product is 3,4,5-trimethyl-4
-dichloromethyl-2,5-cyclohexadienone, 95% of which is 3,4,5-trimethyl-2-
It was formylphenol. That is, the yield of the target product was 5% and the selectivity was 13%. Comparative Example 4 Through the same experimental procedure as in Comparative Example 1, 1 g of P-
1 g of ar-2-tetrahydronaphthol was used instead of cresol, yielding 0.52 g of product.
19% of the product was 9-dichloromethyl-6-oxo-1,2,3,4,6,9-hexahydronaphthalene and 81% was 1-formyl-ar-2-tetrahydronaphthol. That is, the yield of the target product was 10% and the selectivity was 19%. Comparative Example 5 The same operation as in Example 1 was carried out by adding chloroform all at once at the beginning of the reaction instead of gradually adding it dropwise. As a result, the yield of 4-dichloromethyl-4-methyl-2,5-cyclohexadiene was 56%, and the selectivity was 78%.
Claims (1)
トリウムまたは水酸化カリウム、および(c)シクロ
デキストリンを含む水溶液に、ハロホルムを徐々
に滴下することを特徴とする４位のジハロメチル
化された２，５−シクロヘキサジエノン誘導体の
製造法。1. Dihalomethylation at the 4-position characterized by gradually dropping haloform into an aqueous solution containing (a) a para-substituted phenol derivative, (b) sodium hydroxide or potassium hydroxide, and (c) cyclodextrin. A method for producing a 2,5-cyclohexadienone derivative.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56032542A JPS57146734A (en) | 1981-03-09 | 1981-03-09 | Synthetic method of 2,5-cyclohexadienone derivative |
| PCT/JP1982/000066 WO1982003073A1 (en) | 1981-03-09 | 1982-03-09 | Process for introducing substituent to p-position of phenols |
| DE8282900665T DE3274104D1 (en) | 1981-03-09 | 1982-03-09 | Process for selectively producing para-substituted derivatives of phenols |
| DE8484112783T DE3276858D1 (en) | 1981-03-09 | 1982-03-09 | A process for producing a para-substituted phenol derivative |
| EP19840112783 EP0158709B1 (en) | 1981-03-09 | 1982-03-09 | A process for producing a para-substituted phenol derivative |
| EP82900665A EP0073837B1 (en) | 1981-03-09 | 1982-03-09 | Process for selectively producing para-substituted derivatives of phenols |
| US06/530,157 US4523037A (en) | 1981-03-09 | 1983-09-07 | Process for selectively producing para-substituted derivatives of phenols |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56032542A JPS57146734A (en) | 1981-03-09 | 1981-03-09 | Synthetic method of 2,5-cyclohexadienone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57146734A JPS57146734A (en) | 1982-09-10 |
| JPH0128731B2 true JPH0128731B2 (en) | 1989-06-05 |
Family
ID=12361815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56032542A Granted JPS57146734A (en) | 1981-03-09 | 1981-03-09 | Synthetic method of 2,5-cyclohexadienone derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS57146734A (en) |
-
1981
- 1981-03-09 JP JP56032542A patent/JPS57146734A/en active Granted
Non-Patent Citations (1)
| Title |
|---|
| PHARMAZIE=1978 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57146734A (en) | 1982-09-10 |
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