JP3258043B2 - Method for producing benzoate derivative - Google Patents
Method for producing benzoate derivativeInfo
- Publication number
- JP3258043B2 JP3258043B2 JP24651291A JP24651291A JP3258043B2 JP 3258043 B2 JP3258043 B2 JP 3258043B2 JP 24651291 A JP24651291 A JP 24651291A JP 24651291 A JP24651291 A JP 24651291A JP 3258043 B2 JP3258043 B2 JP 3258043B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- acetal
- solvent
- mol
- benzoate derivative
- 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
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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【0001】[0001]
【産業上の利用分野】本発明は新規な安息香酸エステル
誘導体の新規な製造方法に関するものである。さらに詳
しくいえば、本発明は、農薬や医薬品などの合成中間体
として有用な安息香酸エステル誘導体を収率よく製造す
る方法に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel method for producing a novel benzoate derivative. More specifically, the present invention relates to a method for producing a benzoate derivative useful as a synthetic intermediate for agricultural chemicals, pharmaceuticals, and the like with a high yield.
【0002】[0002]
【従来の技術】一般式[Prior Art] General formula
【化3】 (式中のR1は水素原子又はヒドロキシル基の保護基、
R2、R3及びR4はそれぞれ低級アルキル基であり、そ
れらはたがいに同一でも、異なっていてもよい)で表わ
される安息香酸エステル誘導体は、農薬や医薬品の合成
中間体として有用であり、例えば本発明者らが先に見出
した除草活性を有する化合物(特開平4−134073
号公報)の製造中間体として用いられる。Embedded image (Wherein R 1 is a protecting group for a hydrogen atom or a hydroxyl group,
R 2 , R 3 and R 4 are each a lower alkyl group, which may be the same or different.) The benzoate derivative represented by the formula (1) is useful as a synthetic intermediate for agricultural chemicals and pharmaceuticals, For example, a compound having a herbicidal activity previously found by the present inventors (Japanese Patent Laid-Open No. 4-140773).
JP-A No. 195/1992).
【0003】ところで、一般に、置換基に酸素又は窒素
のような不対電子を有するモノ置換ベンゼンにブチルリ
チウムのリチオ化剤を反応させると、置換基のオルト位
がリチオ化され、それに求電子試薬を作用させると高選
択的にオルト誘導体が得られることは古くから知られて
いる[「化学」第45巻、第144ページ(1990
年);「オルガニック・リアクション(Organic
Reaction)」第26巻、第1ページ(197
9年)参照]。そしてこの際、反応溶媒として、通常エ
ーテル、テトラヒドロフランなどのエーテル系溶媒が用
いられるが、ヘキサンなどの炭化水素系溶媒を用いる場
合には、テトラメチルエチレンジアミンなどのリチウム
イオンのキレート剤を必要とすることも知られている。In general, when a butyllithium lithiation agent is reacted with a monosubstituted benzene having an unpaired electron such as oxygen or nitrogen in the substituent, the ortho position of the substituent is lithiated, and the electrophilic reagent It has been known for a long time that ortho derivatives can be obtained by the action of the compound [Chemistry, Vol. 45, p. 144 (1990).
Year); "Organic Reaction"
Reaction), Vol. 26, page 1 (197
9)). In this case, ether solvents such as ether and tetrahydrofuran are usually used as a reaction solvent, but when a hydrocarbon solvent such as hexane is used, a chelating agent for lithium ions such as tetramethylethylenediamine is required. Is also known.
【0004】本発明者らは、これらの知見に基づき、前
記一般式(I)で表される安息香酸エステル誘導体を製
造するために、エーテル系溶媒中において、一般式Based on these findings, the present inventors have proposed a method for producing a benzoate derivative represented by the aforementioned general formula (I) in an ether-based solvent.
【化4】 (式中のR1、R3及びR4は前記と同じ意味をもつ) で表わされるアセタール誘導体に、ブチルリチウム及び
一般式XCOOR2(III)(式中のXはハロゲン原
子、R2は前記と同じ意味をもつ) で表わされるハロゲン酸エステルを順次反応させること
を試みたが、意外にも前記一般式(I)で表わされる安
息香酸誘導体はほとんど生成しなかった。Embedded image (Wherein R 1 , R 3 and R 4 have the same meanings as described above), butyllithium and a general formula XCOOR 2 (III) (wherein X is a halogen atom and R 2 is Have the same meaning as described above), but surprisingly, almost no benzoic acid derivative represented by the general formula (I) was formed.
【0005】[0005]
【発明が解決しようとする課題】本発明は、農薬や医薬
品の合成中間体などとして有用な前記一般式(I)で表
わされる安息香酸エステル誘導体を収率よく製造するた
めの新規な方法を提供することを目的としてなされたも
のである。DISCLOSURE OF THE INVENTION The present invention provides a novel method for producing a benzoate derivative represented by the above general formula (I), which is useful as an intermediate for the synthesis of agricultural chemicals or pharmaceuticals, in a high yield. It was done for the purpose of doing.
【0006】[0006]
【課題を解決するための手段】本発明者らは、前記目的
を達成するために鋭意研究を重ねた結果、意外にも脂肪
族又は芳香族炭化水素を溶媒として用い、前記一般式
(II)で表わされるアセタール誘導体にアルキルリチ
ウム及びハロギ酸エステルを順次反応させることによ
り、所望の安息香酸エステル誘導体が収率よく得られる
ことを見出し、この知見に基づいて本発明を完成するに
至った。Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, unexpectedly, an aliphatic or aromatic hydrocarbon was used as a solvent, and It has been found that a desired benzoate derivative can be obtained in good yield by sequentially reacting an alkyl lithium and a haloformate with the acetal derivative represented by the formula, and the present invention has been completed based on this finding.
【0007】すなわち、本発明は、脂肪族又は芳香族炭
化水素溶媒の存在下、一般式That is, the present invention relates to a compound represented by the general formula (1) in the presence of an aliphatic or aromatic hydrocarbon solvent:
【化5】 (式中のR1、R3及びR4は前記と同じ意味をもつ) で表わされるアセタール誘導体に、アルキルリチウム及
び一般式XCOOR2(III)(式中のX及びR2は前
記と同じ意味をもつ) で表わされるハロギ酸エステルを順次反応させることを
特徴とする、一般式Embedded image (Wherein R 1 , R 3 and R 4 have the same meaning as described above), alkyl lithium and general formula XCOOR 2 (III) (wherein X and R 2 have the same meanings as above) Wherein the haloformate represented by the general formula is sequentially reacted:
【化6】 (式中のR1、R2、R3及びR4は前記と同じ意味をも
つ) で表わされる安息香酸エステル誘導体の製造方法を提供
するものである。Embedded image (Wherein R 1 , R 2 , R 3, and R 4 have the same meanings as described above).
【0008】前記一般式(I)及び(II)におけるR
1は水素原子又はヒドロキシル基の保護基であり、この
保護基についてはヒドロキシル基の保護基として公知の
ものの中から任意に選ぶことができ、特に制限はない。
通常ヒドロキシル基の保護基として慣用されている基と
しては、例えばメチル基、ベンジル基、置換ベンジル
基、メトキシメチル基、エトキシエチル基、tert‐
ブチルジメチルシリル基などが挙げられる。[0008] In general formulas (I) and (II), R
1 is a protecting group for a hydrogen atom or a hydroxyl group. The protecting group can be arbitrarily selected from those known as hydroxyl group protecting groups, and is not particularly limited.
Groups commonly used as protecting groups for hydroxyl groups include, for example, methyl, benzyl, substituted benzyl, methoxymethyl, ethoxyethyl, tert-
And a butyldimethylsilyl group.
【0009】前記一般式(II)で表わされるアセター
ル誘導体としては、例えば3‐ベンジルオキシアセトフ
ェノンジメチルアセタール、3‐ベンジルオキシアセト
フェノンジエチルアセタール、3‐メトキシメトキシア
セトフェノンジメチルアセタールなどが挙げられる。こ
れらのアセタール誘導体は、対応するアセトフェノン誘
導体にオルトギ酸エステルを反応させることにより容易
に得ることができる。Examples of the acetal derivative represented by the general formula (II) include 3-benzyloxyacetophenone dimethyl acetal, 3-benzyloxyacetophenone diethyl acetal, and 3-methoxymethoxyacetophenone dimethyl acetal. These acetal derivatives can be easily obtained by reacting the corresponding acetophenone derivative with an orthoformate.
【0010】本発明方法によると、脂肪族又は芳香族炭
化水素溶媒中において、前記アセタール誘導体にアルキ
ルリチウム及び一般式(III)で表わされるハロギ酸
エステルを順次反応させることにより、前記一般式
(I)で表わされる安息香酸エステル誘導体が高収率か
つ高選択率で得られる。According to the method of the present invention, the acetal derivative is reacted with an alkyl lithium and a haloformate represented by the general formula (III) sequentially in an aliphatic or aromatic hydrocarbon solvent, thereby obtaining the compound represented by the general formula (I) The benzoate derivative represented by the formula (1) is obtained in high yield and high selectivity.
【0011】該アルキルリチウムとしては、例えばメチ
ルリチウム、ブチルリチウム、sec‐ブチルリチウ
ム、tert‐ブチルリチウム、フェニルリチウムなど
が挙げられ、ハロギ酸エステルとしては、例えばクロロ
ギ酸メチル、クロロギ酸エチル、ブロモギ酸メチルなど
が挙げられる。また反応溶媒として用いる脂肪族炭化水
素としては、例えばヘキサン、シクロヘキサン、ヘプタ
ンなどを、芳香族炭化水素としては、例えばベンゼンや
トルエンなどを挙げることができる。これらの溶媒は単
独で用いてもよいし、2種以上を混合して用いてもよ
い。The alkyllithium includes, for example, methyllithium, butyllithium, sec-butyllithium, tert-butyllithium, phenyllithium, and the like, and the haloformate includes, for example, methyl chloroformate, ethyl chloroformate, bromoformate. Methyl and the like. Further, examples of the aliphatic hydrocarbon used as the reaction solvent include hexane, cyclohexane, heptane and the like, and examples of the aromatic hydrocarbon include benzene and toluene. These solvents may be used alone or in combination of two or more.
【0012】次に、本発明の好ましい実施態様の1例に
ついて説明すると、まず前記溶媒中に、該アセタール誘
導体とアルキルリチウムとを、通常当量比1:1ないし
1:2の割合で加え、室温付近で数時間程度かきまぜた
のち、これにハロギ酸エステルを、アセタール誘導体に
対する当量比が1〜2程度になるような割合で加え、−
10〜50℃の範囲の温度において反応を行う。反応終
了後は、過剰のアルキルリチウムを水などを用いて不活
性化したのち、抽出、洗浄、溶媒留去などの操作を施
し、高純度の安息香酸エステル誘導体を単離する。Next, an example of a preferred embodiment of the present invention will be described. First, the acetal derivative and alkyllithium are added to the above-mentioned solvent at a normal equivalence ratio of 1: 1 to 1: 2. After stirring for about several hours in the vicinity, haloformate was added thereto at a ratio such that the equivalent ratio to the acetal derivative was about 1 to 2,
The reaction is carried out at a temperature in the range from 10 to 50C. After completion of the reaction, excess alkyllithium is inactivated using water or the like, and then operations such as extraction, washing, and solvent distillation are performed to isolate a high-purity benzoate derivative.
【0013】このようにして得られた本発明の安息香酸
エステル誘導体は、弱酸を作用させることにより、容易
にアセタール基を除去することができる。The benzoate derivative of the present invention thus obtained can easily remove an acetal group by the action of a weak acid.
【0014】[0014]
【発明の効果】本発明方法で得られる安息香酸エステル
誘導体は、農薬や医薬品などの合成中間体として有用で
あり、例えば本発明者らが先に見出した除草活性化合物
(特開平4−134073号公報)の製造中間体として
用いられる。The benzoate derivative obtained by the method of the present invention is useful as a synthetic intermediate for agrochemicals and pharmaceuticals, for example, a herbicidally active compound previously discovered by the present inventors (JP-A-4-134073). Official Gazette).
【0015】本発明によると、この安息香酸エステル誘
導体を、高収率かつ高選択率で容易に製造することがで
きる。According to the present invention, the benzoate derivative can be easily produced with high yield and high selectivity.
【0016】[0016]
【実施例】次に、実施例により本発明をさらに詳細に説
明するが、本発明はこれらの例によってなんら限定され
るものではない。Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples.
【0017】実施例1 3‐ベンジルオキシ‐2‐メトキシカルボニルアセトフ
ェノンジメチルアセタールの製造 窒素気流下、3‐ベンジルオキシアセトフェノンジメチ
ルアセタール8.16g(30ミリモル)をトルエン8
0mlに溶解し、0〜5℃にてn‐ブチルリチウムの1
5wt%ヘキサン溶液21ml(n‐ブチルリチウム3
3ミリモル)を滴下した。20℃で2時間かきまぜたの
ち、反応液を再冷却し、クロロギ酸メチル3.12g
(33ミリモル)を5〜10℃にて滴下した。20℃で
2時間かきまぜたのち、酢酸エチル10mlを加え、次
いで反応液を水洗後、溶媒を留去して油状物10.0g
を得た。Example 1 Production of 3-benzyloxy-2-methoxycarbonylacetophenone dimethyl acetal In a nitrogen stream, 8.16 g (30 mmol) of 3-benzyloxyacetophenone dimethyl acetal was added to toluene 8
0 ml, and n-butyllithium 1 at 0-5 ° C.
21 ml of a 5 wt% hexane solution (n-butyl lithium 3
3 mmol) was added dropwise. After stirring at 20 ° C. for 2 hours, the reaction solution was recooled, and methyl chloroformate was 3.12 g.
(33 mmol) was added dropwise at 5-10 ° C. After stirring at 20 ° C. for 2 hours, 10 ml of ethyl acetate was added, and then the reaction solution was washed with water, and the solvent was distilled off to obtain 10.0 g of an oily substance.
I got
【0018】この油状物をガスクロ分析したところ、3
‐ベンジルオキシ‐2‐メトキシカルボニルアセトフェ
ノンジメチルアセタールが73モル%の収率で生成し、
未反応の原料が16モル%残存していることが分った。
次に、この油状物をカラムクロマトグラフィーで精製
し、3‐ベンジルオキシ‐2‐メトキシカルボニルアセ
トフェノンジメチルアセタールの分析標品3.0gを得
た。The oil was analyzed by gas chromatography to find that
-Benzyloxy-2-methoxycarbonylacetophenone dimethyl acetal is produced in a yield of 73 mol%,
It was found that 16 mol% of unreacted raw materials remained.
Next, this oil was purified by column chromatography to obtain 3.0 g of an analytical sample of 3-benzyloxy-2-methoxycarbonylacetophenone dimethyl acetal.
【0019】この標品について赤外吸収スペクトル、N
MRスペクトル及び20℃における屈折率を求めたとこ
ろ次の結果が得られた。 IR(neat):1730,1580,1440,1
260cm-1 NMR(CDCl3):δ1.6(s,3H),3.2
(s,6h),3.8(s,3H),5.1(s,2
H),6.7〜7.6(m,8H) nD 20:1.5413The infrared absorption spectrum, N
When the MR spectrum and the refractive index at 20 ° C. were determined, the following results were obtained. IR (neat): 1730, 1580, 1440, 1
260 cm -1 NMR (CDCl 3 ): δ 1.6 (s, 3H), 3.2
(S, 6h), 3.8 (s, 3H), 5.1 (s, 2
H), 6.7~7.6 (m, 8H ) n D 20: 1.5413
【0020】実施例2 3‐ベンジルオキシ‐2‐メトキシカルボニルアセトフ
ェノンジメチルアセタールの製造 実施例1においてトルエンの代りにn‐ヘキサンを溶媒
として用いた以外は、実施例1と同様に反応した。生成
物をガスクロ分析したところ、3‐ベンジルオキシ‐2
‐メトキシカルボニルアセトフェノンジメチルアセター
ルが60モル%の収率で生成し、原料は24モル%残存
していた。Example 2 Preparation of 3-benzyloxy-2-methoxycarbonylacetophenone dimethyl acetal The reaction was carried out in the same manner as in Example 1 except that n-hexane was used as a solvent instead of toluene. The product was analyzed by gas chromatography and found to be 3-benzyloxy-2.
-Methoxycarbonylacetophenone dimethyl acetal was produced in a yield of 60 mol%, and the raw material remained at 24 mol%.
【0021】実施例3 3‐ベルジルオキシ‐2‐メトキシカルボニルアセトフ
ェノンジメチルアセタールの製造 実施例1において、トルエンの代りにシクロヘキサンを
溶媒として用いた以外は、実施例1と同様に反応した。
生成物をガスクロ分析したところ、3‐ベルジルオキシ
‐2‐メトキシカルボニルアセトフェノンジメチルアセ
タールが83モル%の収率で生成し、原料は6モル%残
存してた。Example 3 Preparation of 3-Berdyloxy-2-methoxycarbonylacetophenone dimethyl acetal The reaction was carried out in the same manner as in Example 1 except that cyclohexane was used as a solvent instead of toluene.
The product was analyzed by gas chromatography. As a result, 3-belzyloxy-2-methoxycarbonylacetophenone dimethyl acetal was produced in a yield of 83 mol%, and 6 mol% of the raw material remained.
【0022】実施例4 3‐ヒドロキシ‐2‐メトキシカルボニルアセトフェノ
ンジメチルアセタールの製造 50ml四つ口反応フラスコに、3‐ベルジルオキシ‐
2‐メトキシカルボニルアセトフェノンジメチルアセタ
ール1.0g(3.0ミリモル)、5wt%パラジウム
‐炭素0.1g、メタノール5ml及びトルエン1ml
を入れ、室温で接触水素添加処理した。8時間後、パラ
ジウム‐炭素をろ別したのち、溶媒を留去して油状物
0.5gを得た。この油状物を1H‐NMRで分析した
ところ、3‐ヒドロキシ‐2‐メトキシカルボニルアセ
トフェノンジメチルアセタールが67モル%、脱アセタ
ール化された3‐ヒドロキシ‐2‐メトキシカルボニル
アセトフェノンが33モル%の組成であった。Example 4 Preparation of 3-hydroxy-2-methoxycarbonylacetophenone dimethyl acetal In a 50 ml four-necked reaction flask, 3-verzyloxy-
1.0 g (3.0 mmol) of 2-methoxycarbonylacetophenone dimethyl acetal, 0.1 g of 5 wt% palladium-carbon, 5 ml of methanol and 1 ml of toluene
And subjected to catalytic hydrogenation treatment at room temperature. After 8 hours, the palladium-carbon was filtered off, and the solvent was distilled off to obtain 0.5 g of an oil. The oil was analyzed by 1 H-NMR to find that the composition of 3-hydroxy-2-methoxycarbonylacetophenone dimethyl acetal was 67 mol% and the deacetalized 3-hydroxy-2-methoxycarbonyl acetophenone was 33 mol%. there were.
【0023】3‐ヒドロキシ‐2‐メトキシカルボニル
アセトフェノンジメチルアセタールの分析標品を少量得
て、分析したところ、次のデータが得られた。 IR(neat):1710,1590,1470,1
440,1300cm-1 NMR(CDC13):δ1.7(s,3H),3.2
(s,6H),3.9(s,3H),6.5〜7.7
(m,4H) nD 20:1.5150A small amount of an analytical sample of 3-hydroxy-2-methoxycarbonylacetophenone dimethyl acetal was obtained and analyzed. The following data was obtained. IR (neat): 1710, 1590, 1470, 1
440,1300cm -1 NMR (CDC1 3): δ1.7 (s, 3H), 3.2
(S, 6H), 3.9 (s, 3H), 6.5-7.7.
(M, 4H) n D 20 : 1.5150
【0024】比較例 実施例1において、トルエンの代りにジエチルエーテル
を溶媒として用いた以外は、実施例1と同様に反応を行
い、ガスクロ分析したところ、3‐ベンジルオキシ‐2
‐メトキシカルボニルアセトフェノンジメチルアセター
ルは2モル%しか生成していなかった。Comparative Example A reaction was carried out in the same manner as in Example 1 except that diethyl ether was used instead of toluene as a solvent, and gas chromatographic analysis showed that 3-benzyloxy-2.
Only 2 mol% of -methoxycarbonylacetophenone dimethyl acetal was formed.
【0025】実施例5 3‐ベンジルオキシ‐2‐エトキシカルボニルアセトフ
ェノンジエチルアセタールの製造 窒素気流下、3‐ベルジルオキシアセトフェノンジエチ
ルアセタール9.0g(30ミリモル)をシクロヘキサ
ン60mlに溶解し、0〜5℃にてn‐ブチルリチウム
の15wt%ヘキサン溶液21ml(n‐ブチルリチウ
ム33ミリモル)を滴下した。20℃で2時間かきまぜ
たのち、反応液を再冷却し、クロロギ酸エチル3.58
g(33ミリモル)を5〜10℃にて滴下した。20℃
で2時間かきまぜたのち、酢酸エチル10mlを加え、
次いで反応液を水洗後、溶媒を留去して油状物11.0
gを得た。Example 5 Preparation of 3-benzyloxy-2-ethoxycarbonylacetophenone diethyl acetal Under a nitrogen stream, 9.0 g (30 mmol) of 3-benzyloxyacetophenone diethyl acetal was dissolved in 60 ml of cyclohexane, and the solution was dissolved at 0 to 5 ° C. Then, 21 ml of a 15 wt% hexane solution of n-butyllithium (33 mmol of n-butyllithium) was added dropwise. After stirring at 20 ° C. for 2 hours, the reaction solution was recooled, and ethyl chloroformate 3.58 was obtained.
g (33 mmol) were added dropwise at 5-10 ° C. 20 ° C
After stirring for 2 hours, add 10 ml of ethyl acetate,
Then, the reaction solution was washed with water and the solvent was distilled off to obtain an oily substance 11.0.
g was obtained.
【0026】この油状物をガスクロ分析したところ、3
‐ベルジルオキシ‐2‐エトキシカルボニルアセトフェ
ノンジエチルアセタールが73モル%の収率で生成し、
未反応の原料が15モル%残存していることが分った。
次に、この油状物をカラムクロマトグラフィーで精製
し、3‐ベルジルオキシ‐2‐エトキシカルボニルアセ
トフェノンジエチルアセタール6.8gを得た。収率は
61モル%であった。このものの分析データを次に示
す。 IR(neat):1720,1580,1440,1
260,1050cm-1 NMR(CDCl3):δ1.2(t,J=7Hz,6
H),1.3(t,J=7Hz,3H),1.6(s,
3H),3.5(q,J=7Hz,4H),4.3
(q,J=7Hz,2H),5.0(s,2H),6.
7〜7.5(m,8H) nD 20:1.5288The oily substance was analyzed by gas chromatography to find that
-Berdyloxy-2-ethoxycarbonylacetophenone diethyl acetal is produced in a yield of 73 mol%,
It was found that 15 mol% of unreacted raw materials remained.
Next, this oily product was purified by column chromatography to obtain 6.8 g of 3-verdyloxy-2-ethoxycarbonylacetophenone diethyl acetal. The yield was 61 mol%. The analytical data of this is shown below. IR (neat): 1720, 1580, 1440, 1
260, 1050 cm -1 NMR (CDCl 3 ): δ 1.2 (t, J = 7 Hz, 6
H), 1.3 (t, J = 7 Hz, 3H), 1.6 (s,
3H), 3.5 (q, J = 7 Hz, 4H), 4.3
(Q, J = 7 Hz, 2H), 5.0 (s, 2H), 6.
7~7.5 (m, 8H) n D 20: 1.5288
【0027】実施例6 3‐ヒドロキシ‐2‐エトキシカルボニルアセトフェノ
ンジエチルアセタールの製造 50ml四つ口反応フラスコに、3‐ベルジルオキシ‐
2‐エトキシカルボニルアセトフェノンジエチルアセタ
ール3.0g(8.0ミリモル)、5wt%パラジウム
‐炭素0.3g、メタノール20ml及びトルエン2m
lを入れ、室温で接触水素添加処理した。8時間後、パ
ラジウム−炭素をろ別したのち、溶媒を留去して結晶
1.7gを得た。Example 6 Preparation of 3-hydroxy-2-ethoxycarbonylacetophenone diethyl acetal In a 50 ml four-necked reaction flask, 3-verzyloxy-
2-ethoxycarbonylacetophenone diethyl acetal 3.0 g (8.0 mmol), 5 wt% palladium-carbon 0.3 g, methanol 20 ml and toluene 2 m
and subjected to catalytic hydrogenation treatment at room temperature. After 8 hours, the palladium-carbon was filtered off, and the solvent was distilled off to obtain 1.7 g of crystals.
【0028】この結晶を1H‐NMRで分析したとこ
ろ、3‐ヒドロキシ‐2‐エトキシカルボニルアセトフ
ェノンジエチルアセタールが83モル%、脱アセタール
化された3‐ヒドロキシ‐2‐エトキシカルボニルアセ
トフェノンが17モル%の組成であった。The crystals were analyzed by 1 H-NMR. As a result, 83 mol% of 3-hydroxy-2-ethoxycarbonylacetophenone diethyl acetal and 17 mol% of deacetalized 3-hydroxy-2-ethoxycarbonylacetophenone were obtained. It was a composition.
【0029】該結晶をヘキサン15mlにより再結晶
し、分析標品として3‐ヒドロキシ‐2‐エトキシカル
ボニルアセトフェノンジエチルアセタール0.5gを得
た。このものの融点は71〜74℃であった。分析デー
タを次に示す。 IR(KBr):1700,1580,1460,12
90,1260cm-1 NMR(CDCl3):δ1.0〜1.5(m,9
H),1.7(s,3H),3.4(q,J=7Hz,
4H),4.4(q,J=7Hz,2H),6.8〜
7.4(m,4H)The crystals were recrystallized from 15 ml of hexane to obtain 0.5 g of 3-hydroxy-2-ethoxycarbonylacetophenone diethyl acetal as an analytical sample. Its melting point was 71-74 ° C. The analysis data is shown below. IR (KBr): 1700, 1580, 1460, 12
90,1260 cm -1 NMR (CDCl 3 ): δ 1.0 to 1.5 (m, 9
H), 1.7 (s, 3H), 3.4 (q, J = 7 Hz,
4H), 4.4 (q, J = 7 Hz, 2H), 6.8-
7.4 (m, 4H)
───────────────────────────────────────────────────── フロントページの続き (72)発明者 木村 芳一 静岡県庵原郡富士川町中之郷2256番地 イハラケミカル工業株式会社研究所内 (56)参考文献 特開 平4−368361(JP,A) 特開 平4−134080(JP,A) 特開 平4−134073(JP,A) (58)調査した分野(Int.Cl.7,DB名) C07C 69/84 C07C 67/36 C07C 69/92 CA(STN) REGISTRY(STN)────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yoshikazu Kimura 2256 Nakanosato, Fujikawa-cho, Anbara-gun, Shizuoka Pref. Ihara Chemical Industry Co., Ltd. (56) References JP-A-4-368361 (JP, A) JP-A Heisei 4-134080 (JP, A) JP-A-4-1344073 (JP, A) (58) Fields investigated (Int. Cl. 7 , DB name) C07C 69/84 C07C 67/36 C07C 69/92 CA (STN ) REGISTRY (STN)
Claims (1)
下、一般式 【化1】 (式中のR1は水素原子又はヒドロキシル基の保護基、
R3及びR4はそれぞれ低級アルキル基であり、それらは
たがいに同一でも、異なっていてもよい) で表わされるアセタール誘導体に、アルキルリチウム及
び一般式XCOOR2(式中のXはハロゲン原子、R2は
低級アルキル基である) で表わされるハロギ酸エステルを順次反応させることを
特徴とする、一般式 【化2】 (式中のR1、R2、R3及びR4は前記と同じ意味をも
つ) で表わされる安息香酸エステル誘導体の製造方法。(1) In the presence of an aliphatic or aromatic hydrocarbon solvent, a compound represented by the general formula: (Wherein R 1 is a protecting group for a hydrogen atom or a hydroxyl group,
R 3 and R 4 are each a lower alkyl group, which may be the same or different from each other. An alkyl lithium and a general formula XCOOR 2 (where X is a halogen atom, R 2 is a lower alkyl group), characterized by sequentially reacting a haloformate represented by the following general formula: (Wherein R 1 , R 2 , R 3 and R 4 have the same meaning as described above).
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP24651291A JP3258043B2 (en) | 1991-09-02 | 1991-09-02 | Method for producing benzoate derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP24651291A JP3258043B2 (en) | 1991-09-02 | 1991-09-02 | Method for producing benzoate derivative |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH0558957A JPH0558957A (en) | 1993-03-09 |
JP3258043B2 true JP3258043B2 (en) | 2002-02-18 |
Family
ID=17149499
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Application Number | Title | Priority Date | Filing Date |
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JP24651291A Expired - Lifetime JP3258043B2 (en) | 1991-09-02 | 1991-09-02 | Method for producing benzoate derivative |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP3258043B2 (en) |
-
1991
- 1991-09-02 JP JP24651291A patent/JP3258043B2/en not_active Expired - Lifetime
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JPH0558957A (en) | 1993-03-09 |
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