JPH04221345A - Production of benzoyl acetic acid esters - Google Patents
Production of benzoyl acetic acid estersInfo
- Publication number
- JPH04221345A JPH04221345A JP41321090A JP41321090A JPH04221345A JP H04221345 A JPH04221345 A JP H04221345A JP 41321090 A JP41321090 A JP 41321090A JP 41321090 A JP41321090 A JP 41321090A JP H04221345 A JPH04221345 A JP H04221345A
- Authority
- JP
- Japan
- Prior art keywords
- group
- atom
- acid esters
- magnesium
- acetophenones
- 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- HXUIDZOMTRMIOE-UHFFFAOYSA-N 3-oxo-3-phenylpropionic acid Chemical class OC(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-N 0.000 title abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- CHKVEDLTACTUAS-UHFFFAOYSA-L magnesium;methyl carbonate Chemical compound [Mg+2].COC([O-])=O.COC([O-])=O CHKVEDLTACTUAS-UHFFFAOYSA-L 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 9
- 150000008062 acetophenones Chemical class 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract 3
- 238000000034 method Methods 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- CXBNMPMLFONTPO-UHFFFAOYSA-N acetic benzoic anhydride Chemical class CC(=O)OC(=O)C1=CC=CC=C1 CXBNMPMLFONTPO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- FAKJFAMIABOKBW-UHFFFAOYSA-N 1-(2,4-dichloro-5-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=C(Cl)C=C1Cl FAKJFAMIABOKBW-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- IVBMCAFPHGSILV-UHFFFAOYSA-N acetyl 3-fluorobenzoate Chemical group C(C)(=O)OC(C1=CC(=CC=C1)F)=O IVBMCAFPHGSILV-UHFFFAOYSA-N 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 2
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000007795 chemical reaction product Substances 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000001569 carbon dioxide Substances 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 238000001816 cooling Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- -1 chloroformic acid ester Chemical class 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
- HXUIDZOMTRMIOE-UHFFFAOYSA-M 3-oxo-3-phenylpropionate Chemical compound [O-]C(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-M 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- POKPUCWXUHWGMX-UHFFFAOYSA-N ethyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC(F)=C(Cl)C=C1Cl POKPUCWXUHWGMX-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- KFCKLKBPBMFRCU-UHFFFAOYSA-N methyl 3-(2,4-dichloro-5-fluorophenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC(F)=C(Cl)C=C1Cl KFCKLKBPBMFRCU-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【0001】0001
【産業上の利用分野】本発明は、キノロンカルボン酸系
合成抗菌剤のための中間原料として有用なベンゾイル酢
酸エステル類の製造方法である。FIELD OF INDUSTRIAL APPLICATION The present invention is a method for producing benzoyl acetates useful as intermediate raw materials for quinolone carboxylic acid-based synthetic antibacterial agents.
【0002】0002
【従来の技術】ベンゾイル酢酸エステル類を製造する方
法として現在最も一般的に行われているのは、下記に示
すごとく、ベンゾイルクロリドをマロン酸ジエチルと反
応させた後、脱炭酸を行う方法である(特公平 2−4
4827号公報など参照)。[Prior Art] Currently, the most common method for producing benzoyl acetates is to react benzoyl chloride with diethyl malonate, followed by decarboxylation, as shown below. (Tokuhei 2-4
(See Publication No. 4827, etc.).
【0003】0003
【化3】[Chemical formula 3]
【0004】また、下記に示すごとく、アセトフェノン
に塩基を作用させた後、炭酸ジエチルと反応させる方法
も知られている(特公平 1−46512号公報参照)
。ただし、下記式において、Xは塩素原子またはフッ素
原子を表し、R7 はアルキル基を表す。[0004] Furthermore, as shown below, a method is known in which acetophenone is reacted with a base and then reacted with diethyl carbonate (see Japanese Patent Publication No. 1-46512).
. However, in the following formula, X represents a chlorine atom or a fluorine atom, and R7 represents an alkyl group.
【0005】[0005]
【化4】[C4]
【0006】[0006]
【発明が解決しようとする課題】従来最も一般的に行わ
れてきた、ベンゾイルクロリドをマロン酸ジエチルと反
応させた後、脱炭酸を行う方法は、脱炭酸の際にしばし
ばアセトフェノンを副生し収率が低下してしまうという
欠点を有する。また、アセトフェノンに塩基を作用させ
た後、炭酸ジエチルと反応させる方法では水素化ナトリ
ウムやリチウムジイソプロピルアミドなどの強塩基を必
要とするが、これは工業生産においては実用的ではない
。[Problems to be Solved by the Invention] The most commonly used method of decarboxylation after reacting benzoyl chloride with diethyl malonate often produces acetophenone as a by-product during decarboxylation. The disadvantage is that the rate decreases. Furthermore, a method in which acetophenone is reacted with a base and then reacted with diethyl carbonate requires a strong base such as sodium hydride or lithium diisopropylamide, which is not practical in industrial production.
【0007】一方、アセトフェノンをマグネシウムメチ
ルカーボネートと反応させた後、酸で処理してベンゾイ
ル酢酸を得るスチルス(Stiles)らの方法[J.
Am. Chem. Soc., 81, 2598
(1959)]では、ベンゾイル酢酸エステル類を得
ることはできない。On the other hand, the method of Stiles et al. [J.
Am. Chem. Soc. , 81, 2598
(1959)], it is not possible to obtain benzoylacetic esters.
【0008】[0008]
【課題を解決するための手段】本発明は従来技術が有し
ていた前記の問題点を解決すべくなされたものであり、
下記化学式(1)で表されるアセトフェノン類をマグネ
シウムメチルカーボネートと反応させ、次いでクロロギ
酸エステル類と反応させることにより、下記化学式(2
)で表されるベンゾイル酢酸エステル類を製造すること
を特徴とするベンゾイル酢酸エステル類の製造方法であ
る。[Means for Solving the Problems] The present invention has been made to solve the above-mentioned problems that the prior art had,
By reacting acetophenones represented by the following chemical formula (1) with magnesium methyl carbonate and then reacting with chloroformates, the following chemical formula (2) can be obtained.
) is a method for producing benzoyl acetates, characterized by producing benzoyl acetates represented by:
【0009】[0009]
【化5】[C5]
【0010】0010
【化6】[C6]
【0011】ただし、R1 、R2 、R3 、R4
、R5 はそれぞれ独立に水素原子、フッ素原子、塩素
原子、臭素原子、ヨウ素原子、低級アルキル基、アルコ
キシル基、アミノ基、アルキルアミノ基、ジアルキルア
ミノ基、あるいはアルキルチオ基を示し、R6 はアル
キル基、シクロアルキル基、アリール基、あるいはアル
アルキル基を示す。[0011] However, R1, R2, R3, R4
, R5 each independently represent a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a lower alkyl group, an alkoxyl group, an amino group, an alkylamino group, a dialkylamino group, or an alkylthio group, and R6 represents an alkyl group, Indicates a cycloalkyl group, aryl group, or aralkyl group.
【0012】従来法では副生物が生じたり工業的に使用
することが困難な強塩基を使用するなどの問題点があっ
たが、本法によればこれらの問題がなくベンゾイル酢酸
エステル類を得ることができる。[0012] Conventional methods had problems such as the generation of by-products and the use of strong bases that were difficult to use industrially, but the present method eliminates these problems and yields benzoyl acetate esters. be able to.
【0013】本法で原料として用いるアセトフェノン類
は、フリーデルクラフツ反応などによって容易に得るこ
とができる。また、マグネシウムメチルカーボネートは
フィンクベイナー(Finkbeiner)らの方法[
J. Org. Chem., 28, 215 (1
963) ]に従って、マグネシウムメチラートを適当
な溶媒中で二酸化炭素と反応させることによって得るこ
とができる。Acetophenones used as raw materials in this method can be easily obtained by Friedel-Crafts reaction or the like. In addition, magnesium methyl carbonate was prepared by the method of Finkbeiner et al. [
J. Org. Chem. , 28, 215 (1
963)] by reacting magnesium methylate with carbon dioxide in a suitable solvent.
【0014】溶媒としては、N,N−ジメチルホルムア
ミド、N,N−ジメチルアセトアミド、N−メチル −
2−ピロリドン、1,3−ジメチル −2−イミダゾリ
ジノン、ジメチルスルホキシド、ジメチルスルホン、ス
ルホラン等を用いることができるが、好ましくはN,N
−ジメチルホルムアミド、N,N−ジメチルアセトアミ
ドである。溶媒の使用量はマグネシウムメチラート1モ
ル当たり 0.1〜1リットル、好ましくは 0.1〜
0.5リットルである。As a solvent, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-
2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, dimethyl sulfone, sulfolane, etc. can be used, but preferably N,N
-dimethylformamide, N,N-dimethylacetamide. The amount of solvent used is 0.1 to 1 liter, preferably 0.1 to 1 liter per mole of magnesium methylate.
It is 0.5 liter.
【0015】本法でベンゾイル酢酸エステルを得るには
、まずマグネシウムメチルカーボネートを上記の溶媒に
溶かした溶液にアセトフェノン類を加えて反応させる。
この際マグネシウムメチルカーボネートをアセトフェノ
ン類に対して1〜10倍モル、好ましくは1〜5倍モル
用い、反応温度80℃〜 150℃、好ましくは 10
0℃〜 140℃で行う。反応時間は 0.1〜10時
間、好ましくは1〜5時間である。To obtain benzoyl acetate using this method, first, acetophenones are added to a solution of magnesium methyl carbonate dissolved in the above-mentioned solvent and reacted. At this time, magnesium methyl carbonate is used 1 to 10 times the mole, preferably 1 to 5 times the mole of acetophenones, and the reaction temperature is 80°C to 150°C, preferably 10 to 10 times the molar amount.
The temperature is 0°C to 140°C. The reaction time is 0.1 to 10 hours, preferably 1 to 5 hours.
【0016】次にこのようにして得られた反応混合物を
同一容器のまま−20℃〜50℃、好ましくは−10℃
〜25℃に冷却し、クロロギ酸エステル類を加える。こ
の際クロロギ酸エステル類はアセトフェノン類に対して
1〜20倍モル、好ましくは1〜5倍モル用い、0.1
〜10時間、好ましくは1〜5時間反応させる。そう
した後、希酸を加えて後処理を行うとベンゾイル酢酸エ
ステル類が得られる。Next, the reaction mixture thus obtained is kept in the same container at -20°C to 50°C, preferably at -10°C.
Cool to ~25°C and add chloroformates. At this time, the chloroformic acid ester is used in a mole of 1 to 20 times, preferably 1 to 5 times the mole of the acetophenone, and 0.1
Allow to react for ~10 hours, preferably 1-5 hours. After that, a dilute acid is added for post-treatment to obtain benzoyl acetates.
【0017】本発明において、R1 、R2 、R3
、R4 およびR5 の少なくとも1つはハロゲン原子
であることが用途の面で好ましい。特に、R4 はフッ
素原子であることが好ましい。また、R1 とR3 の
いずれか少なくとも一方は、特に両方とも、ハロゲン原
子であることが好ましく、そのハロゲン原子は、フッ素
原子、塩素原子、あるいは臭素原子のいずれかであるこ
とが好ましい。特に、R1 とR3 の両方ともが塩素
原子であることが好ましく、ついで一方が塩素原子で他
方がフッ素原子あるいは両方がフッ素原子である場合が
好ましい。In the present invention, R1, R2, R3
, R4 and R5 is preferably a halogen atom in terms of use. In particular, R4 is preferably a fluorine atom. Furthermore, at least one of R1 and R3 is preferably a halogen atom, and the halogen atom is preferably a fluorine atom, a chlorine atom, or a bromine atom. In particular, it is preferable that both R1 and R3 are chlorine atoms, and then one is a chlorine atom and the other is a fluorine atom, or both are preferably fluorine atoms.
【0018】R2 とR5 はいずれもハロゲン原子以
外のもの、即ち水素原子、低級アルキル基、アルコキシ
ル基、アミノ基、アルキルアミノ基、ジアルキルアミノ
基、あるいはアルキルチオ基、であることが好ましく、
特にいずれか一方あるいは両方が水素原子であることが
好ましい。水素原子以外のものであるときは、低級アル
キル基あるいはアルコキシル基が好ましい。R6 はア
ルキル基、シクロアルキル基、アリール基、あるいはア
ルアルキル基であり、特にアルキル基やアルアルキル基
が好ましい。具体的には、メチル基、エチル基、あるい
はベンジル基が最も好ましい。R2 and R5 are both preferably other than a halogen atom, ie, a hydrogen atom, a lower alkyl group, an alkoxyl group, an amino group, an alkylamino group, a dialkylamino group, or an alkylthio group,
In particular, it is preferred that one or both of them be hydrogen atoms. When it is other than a hydrogen atom, a lower alkyl group or an alkoxyl group is preferred. R6 is an alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group, and an alkyl group or an aralkyl group is particularly preferred. Specifically, a methyl group, an ethyl group, or a benzyl group is most preferred.
【0019】上記有機基、即ち、低級アルキル基、アル
キル基、アルコキシル基、アルキルアミノ基、ジアルキ
ルアミノ基、シクロアルキル基、アリール基、およびア
ルアルキル基、の内、低級アルキル基は炭素数1〜4の
アルキル基をいうが、他のアルキル基や他の有機基のア
ルキル基部分の炭素数は必ずしもこれに限定されるもの
ではない。しかし、他のアルキル基やアルキル基部分も
好ましくは低級アルキル基である。また、シクロアルキ
ル基としてはシクロヘキシル基あるいはその低級アルキ
ル基置換体が好ましく、アリール基としてはフェニル基
またはその低級アルキル基あるいはハロゲン原子置換体
が好ましく、アルアルキル基としてはベンジル基または
その低級アルキル基あるいはハロゲン原子置換体が好ま
しい。Among the above organic groups, ie, lower alkyl groups, alkyl groups, alkoxyl groups, alkylamino groups, dialkylamino groups, cycloalkyl groups, aryl groups, and aralkyl groups, the lower alkyl groups have 1 to 1 carbon atoms. 4, but the number of carbon atoms in other alkyl groups and the alkyl group portion of other organic groups is not necessarily limited to this. However, other alkyl groups and alkyl group moieties are also preferably lower alkyl groups. Further, the cycloalkyl group is preferably a cyclohexyl group or its lower alkyl group substituted product, the aryl group is preferably a phenyl group or its lower alkyl group, or its substituted product with a halogen atom, and the aralkyl group is preferably a benzyl group or its lower alkyl group. Alternatively, a halogen atom substituted product is preferable.
【0020】以下、実施例により本発明を説明するが、
本発明はこれら実施例に限定されるものではない。[0020] The present invention will be explained below with reference to Examples.
The present invention is not limited to these examples.
【0021】[0021]
【実施例】[参考例]
マグネシウムメチルカーボネートの調製メタノール60
mlに切削片状のマグネシウム0.1gを加え、還流が
開始されるまで加熱した。マグネシウム表面で反応が開
始された後、還流が継続される程度の速度で切削片状の
マグネシウム 2.4g(100mmol)を1時間か
けて加えた。室温で1時間攪拌後、減圧下で過剰のメタ
ノールを留去すると白色塩が析出した。N,N−ジメチ
ルホルムアミド50mlを加えて懸濁液とし、ガス状の
二酸化炭素17.6g(400mmol)を1時間かけ
て吹き込むと、無色透明溶液が得られた。この溶液を
130℃まで加熱し、若干残っているメタノールを完全
に留去した。[Example] [Reference example] Preparation of magnesium methyl carbonate Methanol 60
ml was added with 0.1 g of magnesium in the form of cut pieces, and heated until reflux started. After the reaction started on the magnesium surface, 2.4 g (100 mmol) of magnesium in the form of cut pieces was added over 1 hour at a rate that continued reflux. After stirring at room temperature for 1 hour, excess methanol was distilled off under reduced pressure to precipitate a white salt. 50 ml of N,N-dimethylformamide was added to form a suspension, and 17.6 g (400 mmol) of gaseous carbon dioxide was blown into the suspension over 1 hour to obtain a colorless and transparent solution. This solution
The mixture was heated to 130°C to completely distill off some remaining methanol.
【0022】[実施例1]参考例で得られたマグネシウ
ムメチルカーボネートのN,N−ジメチルホルムアミド
溶液50mlに2’,4’−ジクロロ −5’フルオロ
アセトフェノン 10.3g(50mmol)を加え、
130 ℃で1時間攪拌した。0℃に冷却した後、クロ
ロギ酸メチル5.7g(60mmol)を加えて2時間
攪拌した。この溶液に氷 50gと1N塩酸 150m
lを加えると二酸化炭素が発生した。有機層を分離し、
水層からジクロロメタン40mlずつで2回抽出し、合
わせた有機層を濃縮乾固させることによって2,4−ジ
クロロ −5−フルオロベンゾイル酢酸メチル 12.
2g (収率 92%)を得た。この状態でも良好な純
度のものであるが、必要ならばさらに減圧蒸留によって
精製することができる(沸点 120〜125 ℃/1
mmHg)。[Example 1] 10.3 g (50 mmol) of 2',4'-dichloro-5'fluoroacetophenone was added to 50 ml of the N,N-dimethylformamide solution of magnesium methyl carbonate obtained in Reference Example.
The mixture was stirred at 130°C for 1 hour. After cooling to 0° C., 5.7 g (60 mmol) of methyl chloroformate was added and stirred for 2 hours. Add 50g of ice and 150ml of 1N hydrochloric acid to this solution.
When 1 was added, carbon dioxide was generated. Separate the organic layer;
Methyl 2,4-dichloro-5-fluorobenzoylacetate was extracted by extracting the aqueous layer twice with 40 ml of dichloromethane each time and concentrating the combined organic layers to dryness.12.
2g (yield 92%) was obtained. Although it is of good purity in this state, it can be further purified by vacuum distillation if necessary (boiling point 120-125 °C/1
mmHg).
【0023】[実施例2]マグネシウムメチラート 8
.6g(100mmol)にN,N−ジメチルホルムア
ミド50mlを加えた懸濁液にガス状の二酸化炭素17
.6g(400mmol)を1時間かけて吹き込んだ。
得られた無色透明溶液に2’,4’−ジクロロ−5’−
フルオロアセトフェノン 10.3g(50mmol)
を加え、130 ℃で1時間攪拌した。0℃に冷却した
後、クロロギ酸メチル5.7g(60mmol)を加え
て2時間攪拌した。この溶液に氷 50gと1N塩酸
150mlを加えると二酸化炭素が発生した。有機層を
分離し、水層からジクロロメタン40mlずつで2回抽
出し、合わせた有機層を濃縮乾固させることによって2
,4−ジクロロ −5−フルオロベンゾイル酢酸メチル
12.5g(収率 94%)を得た。[Example 2] Magnesium methylate 8
.. Gaseous carbon dioxide 17 was added to a suspension of 6 g (100 mmol) and 50 ml of N,N-dimethylformamide.
.. 6 g (400 mmol) was blown into the solution over 1 hour. 2',4'-dichloro-5'-
Fluoroacetophenone 10.3g (50mmol)
was added and stirred at 130°C for 1 hour. After cooling to 0° C., 5.7 g (60 mmol) of methyl chloroformate was added and stirred for 2 hours. Add 50g of ice and 1N hydrochloric acid to this solution.
Carbon dioxide was generated when 150 ml was added. The organic layer was separated, the aqueous layer was extracted twice with 40 ml of dichloromethane, and the combined organic layers were concentrated to dryness.
, 12.5 g (yield 94%) of methyl 4-dichloro-5-fluorobenzoylacetate was obtained.
【0024】[実施例3]参考例で得られたマグネシウ
ムメチルカーボネートのN,N−ジメチルホルムアミド
溶液 3.1mlに2’,4’−ジクロロ−5’−フル
オロアセトフェノン0.46g(3.1mmol)を加
え、 130℃で1時間攪拌した。0℃に冷却した後、
クロロギ酸エチル0.41g(3.7mmol)を加え
て2時間攪拌した。この溶液に氷3g と1N塩酸 9
mlを加えると二酸化炭素が発生した。有機層を分離し
、水層からジクロロメタン 5mlずつで2回抽出し、
合わせた有機層を濃縮した後、減圧蒸留して2,4−ジ
クロロ −5−フルオロベンゾイル酢酸エチル 0.7
1g(収率 82%)を得た。[Example 3] 0.46 g (3.1 mmol) of 2',4'-dichloro-5'-fluoroacetophenone was added to 3.1 ml of the N,N-dimethylformamide solution of magnesium methyl carbonate obtained in Reference Example. was added and stirred at 130°C for 1 hour. After cooling to 0°C,
0.41 g (3.7 mmol) of ethyl chloroformate was added and stirred for 2 hours. To this solution, add 3 g of ice and 9 g of 1N hydrochloric acid.
ml was added and carbon dioxide was evolved. The organic layer was separated, and the aqueous layer was extracted twice with 5 ml of dichloromethane each.
The combined organic layers were concentrated and then distilled under reduced pressure to give 0.7 ethyl 2,4-dichloro-5-fluorobenzoylacetate.
1 g (yield 82%) was obtained.
【0025】[実施例4]参考例で得られたマグネシウ
ムメチルカーボネートのN,N−ジメチルホルムアミド
溶液 3.5mlに2’,4’−ジクロロ−5’−フル
オロアセトフェノン0.37g(1.8mmol)を加
え、 130℃で1時間攪拌した。0℃に冷却した後、
クロロギ酸ベンジル0.48g(2.8mmol)を加
えて2時間攪拌した。この溶液に氷2gと1N塩酸 6
mlを加えると二酸化炭素が発生した。有機層を分離し
、水層からジクロロメタン 5mlずつで2回抽出し、
合わせた有機層を濃縮した後、シリカゲルクロマトグラ
フィーで精製して、2,4−ジクロロ −5−フルオロ
ベンゾイル酢酸ベンジル 0.37g(収率 62%)
を得た。[Example 4] 0.37 g (1.8 mmol) of 2',4'-dichloro-5'-fluoroacetophenone was added to 3.5 ml of the N,N-dimethylformamide solution of magnesium methyl carbonate obtained in Reference Example. was added and stirred at 130°C for 1 hour. After cooling to 0°C,
0.48 g (2.8 mmol) of benzyl chloroformate was added and stirred for 2 hours. Add 2 g of ice and 1N hydrochloric acid to this solution.
ml was added and carbon dioxide was evolved. The organic layer was separated, and the aqueous layer was extracted twice with 5 ml of dichloromethane each.
The combined organic layers were concentrated and purified by silica gel chromatography to give 0.37 g of benzyl 2,4-dichloro-5-fluorobenzoylacetate (yield 62%).
I got it.
【0026】[0026]
【発明の効果】本発明は、従来法に比較して反応におけ
る副生物が少なく、その結果収率の高いベンゾイル酢酸
エステルの製造法である。またこの方法は、従来法で必
要とした強塩基を必要としない方法であり、工業的な実
施が容易である。Effects of the Invention The present invention is a method for producing benzoyl acetate, which produces fewer by-products in the reaction than conventional methods and, as a result, has a high yield. Moreover, this method does not require the strong base required in the conventional method, and is easy to implement industrially.
Claims (4)
ン類をマグネシウムメチルカーボネートと反応させ、次
いでクロロギ酸エステル類と反応させることにより、下
記化学式(2)で表されるベンゾイル酢酸エステル類を
製造することを特徴とするベンゾイル酢酸エステル類の
製造方法。 【化1】 【化2】 ただし、R1 、R2 、R3 、R4 、R5 はそ
れぞれ独立に水素原子、フッ素原子、塩素原子、臭素原
子、ヨウ素原子、低級アルキル基、アルコキシル基、ア
ミノ基、アルキルアミノ基、ジアルキルアミノ基、ある
いはアルキルチオ基を示し、R6はアルキル基、シクロ
アルキル基、アリール基、あるいはアルアルキル基を示
す。Claim 1: Manufacture benzoyl acetates represented by the following chemical formula (2) by reacting acetophenones represented by the following chemical formula (1) with magnesium methyl carbonate and then reacting with chloroformates. A method for producing benzoyl acetates, characterized by: [Chemical 1] [Chemical 2] However, R1, R2, R3, R4, and R5 are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a lower alkyl group, an alkoxyl group, an amino group, an alkylamino group. R6 represents an alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group.
子、塩素原子あるいは臭素原子であり、R4 がフッ素
原子であり、R2 、R5 がいずれも水素原子である
、請求項1の方法。2. The method according to claim 1, wherein R1 and R3 are each independently a fluorine atom, a chlorine atom, or a bromine atom, R4 is a fluorine atom, and R2 and R5 are both hydrogen atoms.
ジル基である、請求項1の方法。3. The method according to claim 1, wherein R6 is a methyl group, an ethyl group or a benzyl group.
’−ジクロロ−5’−フルオロアセトフェノンであり、
化学式(2)で表される化合物が2,4−ジクロロ −
5−フルオロベンゾイル酢酸エステル類である、請求項
1の方法。Claim 4: The compound represented by the chemical formula (1) is 2',4
'-dichloro-5'-fluoroacetophenone,
The compound represented by chemical formula (2) is 2,4-dichloro -
2. The method of claim 1, wherein the ester is a 5-fluorobenzoyl acetate.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP41321090A JP2882057B2 (en) | 1990-12-21 | 1990-12-21 | Method for producing benzoyl acetates |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP41321090A JP2882057B2 (en) | 1990-12-21 | 1990-12-21 | Method for producing benzoyl acetates |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH04221345A true JPH04221345A (en) | 1992-08-11 |
JP2882057B2 JP2882057B2 (en) | 1999-04-12 |
Family
ID=18521893
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Application Number | Title | Priority Date | Filing Date |
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JP41321090A Expired - Lifetime JP2882057B2 (en) | 1990-12-21 | 1990-12-21 | Method for producing benzoyl acetates |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP2882057B2 (en) |
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1990
- 1990-12-21 JP JP41321090A patent/JP2882057B2/en not_active Expired - Lifetime
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---|---|
JP2882057B2 (en) | 1999-04-12 |
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