JPH021823B2 - - Google Patents
Info
- Publication number
- JPH021823B2 JPH021823B2 JP57174895A JP17489582A JPH021823B2 JP H021823 B2 JPH021823 B2 JP H021823B2 JP 57174895 A JP57174895 A JP 57174895A JP 17489582 A JP17489582 A JP 17489582A JP H021823 B2 JPH021823 B2 JP H021823B2
- Authority
- JP
- Japan
- Prior art keywords
- methylene chloride
- dichloro
- dichlorophenol
- hydroxyacetophenone
- yield
- 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 - Lifetime
Links
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- XSJDGJRHRDWQOR-UHFFFAOYSA-N (2,5-dichlorophenyl) acetate Chemical compound CC(=O)OC1=CC(Cl)=CC=C1Cl XSJDGJRHRDWQOR-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- RANCECPPZPIPNO-UHFFFAOYSA-N 2,5-dichlorophenol Chemical compound OC1=CC(Cl)=CC=C1Cl RANCECPPZPIPNO-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 2
- FXCLIEYDXXVEAI-UHFFFAOYSA-N benzene;dichloromethane Chemical compound ClCCl.C1=CC=CC=C1 FXCLIEYDXXVEAI-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XGIAHMUOCFHQTI-UHFFFAOYSA-N Cl.Cl.Cl.Cl.CC Chemical compound Cl.Cl.Cl.Cl.CC XGIAHMUOCFHQTI-UHFFFAOYSA-N 0.000 description 1
- 241001061260 Emmelichthys struhsakeri Species 0.000 description 1
- 238000005618 Fries rearrangement reaction Methods 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WIRUZQNBHNAMAB-UHFFFAOYSA-N benzene;cyclohexane Chemical compound C1CCCCC1.C1=CC=CC=C1 WIRUZQNBHNAMAB-UHFFFAOYSA-N 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000004816 dichlorobenzenes Chemical class 0.000 description 1
- -1 dichlorophenyl 2-tetrahydropyranyl ether Chemical compound 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 238000001256 steam distillation Methods 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
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は３，６―ジクロル―２―ヒドロキシア
セトフエノンの合成法に関する。
３，６―ジクロル―２―ヒドロキシアセトフエ
ノンは医薬品、農薬などの中間原料として重要で
ある。その合成法としては、従来２，５―ジクロ
ルフエノールにアセチレンジカルボン酸ジメチル
エステルを反応させる工程を含む３工程からなる
方法［特開昭50−52070］および２，５―ジクロ
ル―フエノールアセテートと塩化アルミニウムを
155〜165℃で1.5時間反応させる方法［Przem.
Chem.58、533（1979）］が知られている。しかし
ながら、前者は工程数が長いこと、試剤として使
用するアセチレンジカルボン酸ジメチルエステル
が高価であること、全収率が35.2％と低いことな
どの欠点があり、また後者は記載収率57％である
が、フエノール性水酸基をメチル化して単離して
いるため、そのままの状態として副生物２，５―
ジクロル―４―ヒドロキシアセトフエノンとの分
離についての配慮がされていないことに欠点があ
る。また後者の収率についても後述のとおり正確
さを欠く難がある。
本発明者らは、溶媒中で塩化アルミニウムの存
在下フリース転位を試みたところ、従来法で無溶
媒であつた反応を溶液状態で実施することにより
パラ異性体の生成を抑え、目的とするオルト体の
選択率を高めることを見出し、本発明を完成し
た。
本発明の要旨は、溶媒中塩化アルミニウムの存
在下２，５―ジクロルフエノールアセテートを加
熱して３，６―ジクロル―２―ヒドロキシアセト
フエノンを得る点にある。
溶媒としてはニトロベンゼン、二硫化炭素、四
塩化エタン、ジクロルベンゼン類などが挙げられ
るが、とくにニトロベンゼンが好ましい。本反応
は一般に100〜180℃好ましくは120〜150℃にて、
必要なら１〜50気圧の加圧下に実施される。反応
を促進させるために無水酢酸を添加してもよい。
なお二硫化炭素を使用する方法として、反応を二
硫化炭素中で開始したのち、二硫化炭素を留去
し、さらに無溶媒下に反応を完結させる方法を採
用してもよい。
生成した異性体などの混合物の分離のためには
種々の有機化合物の分離法が採用されるが、水蒸
気蒸留が好ましい。なお３，４―ジヒドロ―2H
―ピランを使用して、一旦テトラヒドロピラニル
エーテルとして分離してもよい。
以下に本発明の実施例および比較例を示す。
実施例 １
２，５―ジクロルフエノールアセテート10ｇお
よび無水塩化アルミニウム19.5ｇをニトロベンゼ
ンに溶かし、これに無水酢酸9.96ｇを徐々に加
え、混合物を浴温130℃の油浴上で６時間加熱す
る。反応液を氷水にあけ、ベンゼンで抽出する。
ベンゼン層を水洗し、減圧濃縮する。残渣にメタ
ノール50mlおよび10％水酸化ナトリウム水溶液50
mlを加え、水浴上15分間還流し、メタノールを減
圧留去する。残留液をベンゼンで抽出して、ニト
ロベンゼンを除去する。水層を塩酸酸性とし、塩
化メチレンで抽出する。塩化メチレン層を水洗
し、芒硝で乾燥し、減圧濃縮する。残渣をシリカ
ゲルによるカラムクロマトグラフイーに付し、ベ
ンゼン―塩化メチレン（１：１）で溶出する。目
的物と２，５―ジクロルフエノールを含む溶出液
を集め、再びこれをローバーカラム（メルク社
製）を使用してクロマトグラフイーに付す。ベン
ゼン―シクロヘキサン（１：１）〜ベンゼン―酢
酸エチル（１：１）で溶出し、溶出液を濃縮する
と、融点50〜54℃の淡黄色結晶として粗生成物
4.58ｇを得る。粗収率45.8％。この結晶を酢酸エ
チル―石油エーテルから再結晶し、融点55〜56℃
の淡黄色プリズム晶として３，６―ジクロル―２
―ヒドロキシアセトフエノン4.2ｇを得る。収率
42％。
元素分析（C8H6O2Cl2として）
計算値：Ｃ，46.86；Ｈ，2.95；
Cl，34.58（％）
実験値：Ｃ，46.66；Ｈ，3.08；
Cl，34.70（％）
IR：νNujol nax 1630，1410，1160，810cm-1
さらに後半の溶出液から２，５―ジクロルフエ
ノール1.74ｇを得る。収率22.0％。
先のシリカゲルカラムから２％メタノール―塩
化メチレンで溶出し、溶出物を濃縮し、４―ヒド
ロキシ―２，５―ジクロルアセトフエノンを得
る。本品を酢酸エチル―イソプロピルエーテルか
ら再結晶すると、融点148〜149℃の結晶となる。
収量300mg。収率3.0％。
元素分析（C8H6O2Cl2として）
計算値：Ｃ，46.86；Ｈ，2.95；
Cl，34.58（％）
実験値：Ｃ，46.84；Ｈ，3.06；
Cl，34.34（％）
IR：νNujol nax 3100，1660，1590，1295，1250cm
-1
実施例 ２
２，５―ジクロルフエノールアセテート10ｇお
よび無水塩化アルミニウム7.8ｇをニトロベンゼ
ン30mlに溶かし、浴温130℃の油浴上で６時間加
熱する。実施例１と同様に処理すると、下記の生
成物を得る。
The present invention relates to a method for synthesizing 3,6-dichloro-2-hydroxyacetophenone. 3,6-Dichloro-2-hydroxyacetophenone is important as an intermediate raw material for pharmaceuticals, agricultural chemicals, etc. Conventional methods for its synthesis include a three-step method including the step of reacting 2,5-dichlorophenol with acetylene dicarboxylic acid dimethyl ester [JP-A-50-52070], and a method involving 2,5-dichlorophenol acetate and chloride. aluminum
Method of reacting at 155-165℃ for 1.5 hours [Przem.
Chem. 58 , 533 (1979)] is known. However, the former has drawbacks such as the long number of steps, the high cost of acetylene dicarboxylic acid dimethyl ester used as a reagent, and a low overall yield of 35.2%, while the latter has a stated yield of 57%. However, since the phenolic hydroxyl group is methylated and isolated, the by-product 2,5-
A drawback is that no consideration is given to separation from dichloro-4-hydroxyacetophenone. Furthermore, the yield of the latter also suffers from a lack of accuracy, as will be described later. The present inventors attempted Fries rearrangement in the presence of aluminum chloride in a solvent, and found that by carrying out the reaction in a solution state, which was conventionally solventless, the formation of the para isomer was suppressed, and the desired ortho The present invention has been completed based on the discovery that the selectivity of the body can be increased. The gist of the present invention is to obtain 3,6-dichloro-2-hydroxyacetophenone by heating 2,5-dichlorophenol acetate in the presence of aluminum chloride in a solvent. Examples of the solvent include nitrobenzene, carbon disulfide, ethane tetrachloride, and dichlorobenzenes, with nitrobenzene being particularly preferred. This reaction is generally carried out at 100-180°C, preferably 120-150°C.
If necessary, it is carried out under increased pressure of 1 to 50 atmospheres. Acetic anhydride may be added to accelerate the reaction.
Note that as a method using carbon disulfide, a method may be adopted in which the reaction is started in carbon disulfide, the carbon disulfide is distilled off, and the reaction is further completed in the absence of a solvent. Although various organic compound separation methods can be employed to separate the resulting mixture of isomers and the like, steam distillation is preferred. In addition, 3,4-dihydro-2H
- Pyran may be used to separate it once as tetrahydropyranyl ether. Examples and comparative examples of the present invention are shown below. Example 1 10 g of 2,5-dichlorophenol acetate and 19.5 g of anhydrous aluminum chloride are dissolved in nitrobenzene, 9.96 g of acetic anhydride is gradually added thereto, and the mixture is heated on an oil bath with a bath temperature of 130° C. for 6 hours. Pour the reaction solution into ice water and extract with benzene.
The benzene layer is washed with water and concentrated under reduced pressure. Add 50 ml of methanol and 50 ml of 10% aqueous sodium hydroxide solution to the residue.
ml and refluxed on a water bath for 15 minutes, and methanol was distilled off under reduced pressure. The residual liquid is extracted with benzene to remove nitrobenzene. The aqueous layer is acidified with hydrochloric acid and extracted with methylene chloride. The methylene chloride layer is washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel and eluted with benzene-methylene chloride (1:1). The eluate containing the target product and 2,5-dichlorophenol is collected and subjected to chromatography again using a Rover column (manufactured by Merck & Co.). Elution with benzene-cyclohexane (1:1) to benzene-ethyl acetate (1:1) and concentration of the eluate yielded the crude product as pale yellow crystals with a melting point of 50-54°C.
Obtain 4.58g. Crude yield 45.8%. These crystals were recrystallized from ethyl acetate-petroleum ether, with a melting point of 55-56℃.
3,6-dichloro-2 as pale yellow prismatic crystals of
- Obtain 4.2 g of hydroxyacetophenone. yield
42%. Elemental analysis (as C 8 H 6 O 2 Cl 2 ) Calculated value: C, 46.86; H, 2.95; Cl, 34.58 (%) Experimental value: C, 46.66; H, 3.08; Cl, 34.70 (%) IR: ν Nujol nax 1630, 1410, 1160, 810 cm -1 Furthermore, 1.74 g of 2,5-dichlorophenol was obtained from the latter eluate. Yield 22.0%. The silica gel column was eluted with 2% methanol-methylene chloride, and the eluate was concentrated to obtain 4-hydroxy-2,5-dichloroacetophenone. When this product is recrystallized from ethyl acetate-isopropyl ether, it becomes crystals with a melting point of 148-149℃.
Yield 300mg. Yield 3.0%. Elemental analysis (as C 8 H 6 O 2 Cl 2 ) Calculated value: C, 46.86; H, 2.95; Cl, 34.58 (%) Experimental value: C, 46.84; H, 3.06; Cl, 34.34 (%) IR: ν Nujol nax 3100, 1660, 1590, 1295, 1250cm
-1 Example 2 10 g of 2,5-dichlorophenol acetate and 7.8 g of anhydrous aluminum chloride are dissolved in 30 ml of nitrobenzene and heated on an oil bath with a bath temperature of 130°C for 6 hours. Working up as in Example 1 gives the following product.
【表】
実施例 ３
実施例１と同様にして得られた反応混合物をシ
リカゲルによるカラムクロマトグラフイーに付
し、２％メタノール―塩化メチレンで溶出する溶
出液を濃縮し、粗生成物4.1ｇを得る。これに３，
４―ジヒドロ―2H―ピラン７ｇ、ピリジン―ｐ
―トルエンスルホン酸複合体100mgおよび塩化メ
チレン50mlを加え、室温下に２時間撹拌する。反
応液に10％水酸化ナトリウムを加え、塩化メチレ
ンで抽出する。水層を塩酸酸性とし、塩化メチレ
ンで抽出する。有機層を水洗し、芒硝で乾燥し、
減圧濃縮すると、融点53〜55℃の結晶として３，
６―ジクロル―２―ヒドロキシアセトフエノン
2.2ｇを得る。
一方塩化メチレン層を水洗し、芒硝で乾燥し、
減圧濃縮する。得られる油状物をシリカゲルにて
カラムクロマトグラフイーに付し、ベンゼン―塩
化メチレンで溶出させ、溶出物を減圧濃縮し、下
記生成物を得る。[Table] Example 3 A reaction mixture obtained in the same manner as in Example 1 was subjected to column chromatography using silica gel, and the eluate eluted with 2% methanol-methylene chloride was concentrated to obtain 4.1 g of the crude product. obtain. 3,
4-dihydro-2H-pyran 7g, pyridine-p
- Add 100 mg of toluenesulfonic acid complex and 50 ml of methylene chloride, and stir at room temperature for 2 hours. Add 10% sodium hydroxide to the reaction solution and extract with methylene chloride. The aqueous layer is acidified with hydrochloric acid and extracted with methylene chloride. The organic layer was washed with water, dried with Glauber's salt,
When concentrated under reduced pressure, 3,
6-dichloro-2-hydroxyacetophenone
Obtain 2.2g. Meanwhile, the methylene chloride layer was washed with water, dried with sodium sulfate,
Concentrate under reduced pressure. The resulting oil was subjected to column chromatography on silica gel, eluted with benzene-methylene chloride, and the eluate was concentrated under reduced pressure to obtain the following product.
【表】
これらのエーテル体は塩酸処理すると、それぞ
れ対応するフエノールを生成する。またエーテル
体は別途合成した標準品と同定される。これは下
記に参考例として示す。
比較例 １〜３
２，５―ジクロルフエノールアセテート10ｇお
よび無水塩化アルミニウム9.76ｇを混合し、所定
の時間所定温度（浴温）で加熱する。冷後、反応
液に少量の水を加え、少し加温して錯塩を分解さ
せ、塩化メチレンで抽出する。塩化メチレン層を
水洗し、芒硝で乾燥し、減圧濃縮する。残渣を実
施例１と同様にカラムクロマトグラフイーに付し
て、下記の生成物を得る。[Table] When these ethers are treated with hydrochloric acid, they produce the corresponding phenols. In addition, the ether form is identified as a separately synthesized standard product. This is shown below as a reference example. Comparative Examples 1 to 3 10 g of 2,5-dichlorophenol acetate and 9.76 g of anhydrous aluminum chloride are mixed and heated at a predetermined temperature (bath temperature) for a predetermined time. After cooling, add a small amount of water to the reaction solution, heat it slightly to decompose the complex salt, and extract with methylene chloride. The methylene chloride layer is washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue is subjected to column chromatography in the same manner as in Example 1 to obtain the following product.
【表】【table】
【表】
参考例 １
２，５―ジクロル―４―ヒドロキシアセトフエ
ノン1.0ｇと塩化メチレン10mlに溶かし、これに
３，４―ジヒドロ―2H―ピラン1.23ｇおよびピ
リジン―ｐ―トルエンスルホン酸複合体14mgを加
え、室温下一夜撹拌する。水酸化ナトリウムアル
カリ性とし、塩化メチレンで抽出する。有機層を
水洗し、乾燥し、濃縮する。残渣をシリカゲルに
てカラムクロマトグラフイーに付して油状物を得
る。これを石油エーテルで洗浄し、融点71〜72℃
の結晶として２，５―ジクロル―４―（２―テト
ラヒドロピラニルオキシ）アセトフエノン950mg
を得る。収率67.4％。
元素分析（C13H14O3Cl2として）
計算値：Ｃ，54.00；Ｈ，4.88；
Cl，24.52（％）
実験値：Ｃ，53.76；Ｈ，4.93；
Cl，24.36（％）
IR：νNujol nax 1675，1590，1260，950cm-1
参考例 ２
３，６―ジクロル―２―ヒドロキシアセトフエ
ノン1.0ｇを塩化メチレン10mlに溶かし、これに
３，４―ジヒドロ―2H―ピラン1.23ｇおよびピ
リジン―ｐ―トルエンスルホン酸複合体14mgを加
え、室温下に３時間撹拌する。反応液を減圧濃縮
し、残渣を水酸化ナトリウムアルカリ性とし、エ
ーテルで抽出する。エーテル層を水洗し、乾燥
し、濃縮すると、融点49〜50℃の結晶として３，
６―ジクロル―２―（２―テトラヒドロピラニル
オキシ）アセトフエノン204mgを得る。収率14.5
％。
元素分析（C13H14O3Cl2として）
計算値：Ｃ，54.00；Ｈ，4.88；
Cl，24.52（％）
実験値：Ｃ，54.04；Ｈ，4.89；
Cl，24.13（％）
IR：νfilm nax 1720，1575，1250，930cm-1
なお水層から原料３，６―ジクロル―２―ヒド
ロキシアセトフエノン760mgを回収する。回収率
76％。
参考例 ３
２，５―ジクロルフエノール１ｇを使用して、
参考例１と同様に反応し、油状物として２，５―
ジクロルフエニル２―テトラヒドロピラニルエー
テル1.39ｇを得る。
元素分析（C11H12Cl2O2として）
計算値：Ｃ，53.46；Ｈ，4.86；
Cl，28.72（％）
実験値：Ｃ，53.24；Ｈ，4.85；
Cl，28.76（％）
IR：νfilm nax 1583，1243，1200cm-1
なお２，５―ジクロルフエノールの回収率は
3.3％である。[Table] Reference example 1 Dissolve 1.0 g of 2,5-dichloro-4-hydroxyacetophenone in 10 ml of methylene chloride, add 1.23 g of 3,4-dihydro-2H-pyran and 14 mg of pyridine-p-toluenesulfonic acid complex, and dissolve at room temperature. Stir overnight. Make alkaline with sodium hydroxide and extract with methylene chloride. Wash the organic layer with water, dry and concentrate. The residue was subjected to column chromatography on silica gel to obtain an oil. This is washed with petroleum ether and has a melting point of 71-72℃.
950 mg of 2,5-dichloro-4-(2-tetrahydropyranyloxy)acetophenone as crystals of
get. Yield 67.4%. Elemental analysis (as C 13 H 14 O 3 Cl 2 ) Calculated value: C, 54.00; H, 4.88; Cl, 24.52 (%) Experimental value: C, 53.76; H, 4.93; Cl, 24.36 (%) IR: ν Nujol nax 1675, 1590, 1260, 950cm -1 Reference example 2 Dissolve 1.0 g of 3,6-dichloro-2-hydroxyacetophenone in 10 ml of methylene chloride, add 1.23 g of 3,4-dihydro-2H-pyran and 14 mg of pyridine-p-toluenesulfonic acid complex, and dissolve at room temperature. Stir for 3 hours. The reaction solution was concentrated under reduced pressure, the residue was made alkaline with sodium hydroxide, and extracted with ether. The ether layer is washed with water, dried, and concentrated to give 3,
204 mg of 6-dichloro-2-(2-tetrahydropyranyloxy)acetophenone is obtained. Yield 14.5
%. Elemental analysis (as C 13 H 14 O 3 Cl 2 ) Calculated value: C, 54.00; H, 4.88; Cl, 24.52 (%) Experimental value: C, 54.04; H, 4.89; Cl, 24.13 (%) IR: ν film nax 1720, 1575, 1250, 930 cm -1 760 mg of raw material 3,6-dichloro-2-hydroxyacetophenone was recovered from the aqueous layer. Recovery rate
76%. Reference example 3 Using 1 g of 2,5-dichlorophenol,
The reaction was carried out in the same manner as in Reference Example 1, and 2,5-
1.39 g of dichlorophenyl 2-tetrahydropyranyl ether is obtained. Elemental analysis (as C 11 H 12 Cl 2 O 2 ) Calculated value: C, 53.46; H, 4.86; Cl, 28.72 (%) Experimental value: C, 53.24; H, 4.85; Cl, 28.76 (%) IR: ν film nax 1583, 1243, 1200cm -1 The recovery rate of 2,5-dichlorophenol is
It is 3.3%.
Claims (1)
クロルフエノールアセテートを加熱することを特
徴とする３，６―ジクロル―２―ヒドロキシアセ
トフエノンの合成法。 ２ 無水酢酸の存在下に反応を行う、特許請求の
範囲第１項の方法。 ３ 溶媒としてニトロベンゼンを使用する、特許
請求の範囲第１項の方法。 ４ 反応温度を120〜150℃とする、特許請求の範
囲第１項の方法。[Claims] 1. A method for synthesizing 3,6-dichloro-2-hydroxyacetophenone, which comprises heating 2,5-dichlorophenol acetate in the presence of aluminum chloride in a solvent. 2. The method according to claim 1, wherein the reaction is carried out in the presence of acetic anhydride. 3. The method of claim 1, using nitrobenzene as the solvent. 4. The method according to claim 1, wherein the reaction temperature is 120 to 150°C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57174895A JPS5965038A (en) | 1982-10-04 | 1982-10-04 | Synthesis of 3,6-dichloro-2-hydroxyacetophenone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57174895A JPS5965038A (en) | 1982-10-04 | 1982-10-04 | Synthesis of 3,6-dichloro-2-hydroxyacetophenone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5965038A JPS5965038A (en) | 1984-04-13 |
| JPH021823B2 true JPH021823B2 (en) | 1990-01-12 |
Family
ID=15986557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57174895A Granted JPS5965038A (en) | 1982-10-04 | 1982-10-04 | Synthesis of 3,6-dichloro-2-hydroxyacetophenone |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5965038A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4745103B2 (en) * | 2006-03-30 | 2011-08-10 | エスケー産業株式会社 | Pipe type horizontal water tank |
-
1982
- 1982-10-04 JP JP57174895A patent/JPS5965038A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5965038A (en) | 1984-04-13 |
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