JPH0155260B2 - - Google Patents
Info
- Publication number
- JPH0155260B2 JPH0155260B2 JP15606481A JP15606481A JPH0155260B2 JP H0155260 B2 JPH0155260 B2 JP H0155260B2 JP 15606481 A JP15606481 A JP 15606481A JP 15606481 A JP15606481 A JP 15606481A JP H0155260 B2 JPH0155260 B2 JP H0155260B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- trifluoropropyl
- reaction
- spectrum
- shows
- 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
- -1 p-(3,3,3-trifluoropropyl)phenylacetic acid Chemical compound 0.000 claims description 8
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 3
- 238000007265 chloromethylation reaction Methods 0.000 claims description 3
- 229960003424 phenylacetic acid Drugs 0.000 claims description 3
- 239000003279 phenylacetic acid Substances 0.000 claims description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 2
- 229940073608 benzyl chloride Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 20
- 238000001228 spectrum Methods 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000011592 zinc chloride Substances 0.000 description 10
- 235000005074 zinc chloride Nutrition 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000000862 absorption spectrum Methods 0.000 description 7
- 238000004949 mass spectrometry Methods 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- NLMURJDGDBEMAB-UHFFFAOYSA-N 3,3,3-trifluoropropylbenzene Chemical compound FC(F)(F)CCC1=CC=CC=C1 NLMURJDGDBEMAB-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- FDMFUZHCIRHGRG-UHFFFAOYSA-N 3,3,3-trifluoroprop-1-ene Chemical compound FC(F)(F)C=C FDMFUZHCIRHGRG-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は新規化合物であるｐ−（３，３，３−
トリフルオロプロピル）フエニル酢酸及びその製
造方法に係わる。
本発明者らは、３，３，３−トリフルオロプロ
ペンの有効利用について鋭意研究を進めており、
３，３，３−トリフルオロプロペンとベンゼンと
の反応によつて得られる（３，３，３−トリフル
オロプロピル）ベンゼンから新規化合物であるｐ
−（３，３，３−トリフルオロプロピル）ベンジ
ルクロライド（以下、化合物と称す）を、次に
化合物から誘導される新規化合物であるｐ−
（３，３，３−トリフルオロプロピル）ベンジル
ニトリル（以下、化合物と称す）を、更に化合
物から誘導される新規化合物であるｐ−（３，
３，３−トリフルオロプロピル）フエニル酢酸
（以下、化合物と称す）を合成し得ることを知
見し、本発明に到達したものである。
本発明の化合物は、（３，３，３−トリフル
オロプロピル）ベンゼンを出発原料とし、これに
クロロメチル化反応をおこなうことにより合成さ
れ得る。次に、化合物に例えば金属シアン化物
を反応させることにより化合物を合成する。更
に、化合物を加水分解することにより化合物
を合成する。
本発明化合物及びは本発明化合物の合成
中間体として有用であり、本発明化合物は抗炎
症剤として有用である。即ち本発明化合物は、
通常のカラゲニン浮腫試験（C.A.Winter、Proc.
Soc.Exp.Biol.Med.111、544（1962）参照）をラ
ツトについて実施すると200mg/Kgの経口投与で25
〜30％の浮腫抑制率を示した。
以下、各化合物の合成方法について説明する。
化合物の合成：
化合物は、いわゆるクロロメチル化反応によ
つて合成し得る。すなわち、下記反応式に示され
るように、（３，３，３−トリフルオロプロピル）
ベンゼンとパラホルムアルデヒドと塩化水素とを
塩化亜鉛の存在下に反応させることにより化合物
を合成する。
反応工程の一例を示す。（３，３，３−トリフ
ルオロプロピル）ベンゼンにパラホルムアルデヒ
ドと塩化亜鉛を懸濁させておき、温度40〜80℃で
激しく撹拌しながら塩化水素ガスを吹込む。パラ
ホルムアルデヒドを数回に分けて加えると反応は
円滑に進行する。又、反応の進行により副生成す
る水が塩化亜鉛を溶かして下層に沈降してくるの
で、随時この塩化亜鉛溶液を抜出し且つ新しい塩
化亜鉛を補給することが好ましい。（３，３，３
−トリフルオロプロピル）ベンゼンの転化率を90
％以上にするのには通常10〜30時間を要する。反
応の進行状態はガスクロマトグラフイで追跡し得
る。反応終了後は反応混合物を分液ロートに移
し、下層（塩化亜鉛水溶液）を分離して除去す
る。上層の有機層にエーテルを加え、水、５％炭
酸水素ナトリウム水溶液、水の順に順次洗滌し、
塩化カルシウムで乾燥後にエーテルを留去して反
応混合物を得る。次に、得られた反応混合物を蒸
留することにより化合物を得る。
化合物の合成：
化合物は下記反応式に示されるように、化合
物をDMSO（Dimethyl Sulfoxide）中でシアン
化カリウム又はシアン化ナトリウムと反応させる
ことによつて容易に合成し得る。
反応温度は40〜50℃が好ましく反応時間は通常
20〜30時間であり、反応の進行状態はガスクロマ
トグラフイで追跡し得る。反応終了後、反応混合
物を過剰の水に注ぎ、次にエーテルで抽出する。
次に、エーテル層を水洗し、塩化カルシウムで乾
燥後にエーテルを留去する。こうして得られた反
応混合物を蒸留することにより化合物を得る。
必要ならばクロロホルム−ｎ−ヘキサン混合溶媒
から再結晶して化合物をさらに精製し得る。
化合物の合成：
化合物は化合物をアルコールに溶かし、こ
れに水酸化カリウムの含水アルコール溶液を加え
てリフラツクス条件下に１〜５時間加熱すること
により得られる。反応終了後、溶媒を留去して後
に水に溶解し、水溶液をベンゼンで洗滌し、次い
で水層に稀塩酸を加えて酸性にすると化合物が
結晶として析出する。含水の70％エタノールから
再結晶することにより、さらに精製し得る。
以下、実施例に基づいて本発明をより詳細に説
明する。しかし乍ら、下記実施例のみに本発明は
限定されるものではない。
実施例 １
撹拌機とリフラツクスコンデンサーを具備して
いる容量２の丸底フラスコに（３，３，３−ト
リフルオロプロピル）ベンゼン530ｇ（3.05M）、
パラホルムアルデヒド28ｇ（0.94M）及び塩化亜
鉛22.5ｇ（0.17M）を仕込み、60℃で激しく撹拌
しながら塩化水素ガスを吹込んだ。反応系内の温
度は72℃まで上昇した。パラホルムアルデヒドは
28ｇずつ４回（総合計140ｇ）アフターチヤージ
し、塩化亜鉛は22.5ｇずつ３回アフターチヤージ
した。また、反応途中で分離してくる塩化亜鉛水
溶液を一度除去した。通算22.5時間反応させた。
反応終了後、分離している塩化亜鉛水溶液を分離
し、有機層にエーテルを加えて、水、５％炭酸水
素ナトリウム水溶液、水の順に順次洗滌し、塩化
カルシウムで乾燥後にエーテルを留去して反応混
合物647ｇを得た。この反応混合物をガスクロマ
トグラフイ及びガスクロマトグラフイ質量分析計
で分析したところ第１表のような結果が得られ
た。
The present invention describes a novel compound p-(3,3,3-
This invention relates to trifluoropropyl) phenyl acetic acid and its production method. The present inventors have been conducting intensive research on the effective use of 3,3,3-trifluoropropene,
A new compound p is obtained from (3,3,3-trifluoropropyl)benzene obtained by the reaction of 3,3,3-trifluoropropene and benzene.
-(3,3,3-trifluoropropyl)benzyl chloride (hereinafter referred to as the compound), then p-
(3,3,3-trifluoropropyl)benzyl nitrile (hereinafter referred to as the compound) is further derived from p-(3,
The present invention was achieved by discovering that 3,3-trifluoropropyl) phenyl acetic acid (hereinafter referred to as a compound) can be synthesized. The compound of the present invention can be synthesized by using (3,3,3-trifluoropropyl)benzene as a starting material and subjecting it to a chloromethylation reaction. Next, a compound is synthesized by reacting the compound with, for example, a metal cyanide. Furthermore, a compound is synthesized by hydrolyzing the compound. The compounds of the present invention are useful as synthetic intermediates for the compounds of the present invention, and the compounds of the present invention are useful as anti-inflammatory agents. That is, the compound of the present invention is
Conventional carrageenan edema test (CAWinter, Proc.
Soc.Exp.Biol.Med. 111 , 544 (1962)) was carried out on rats, and an oral dose of 200 mg/Kg resulted in 25
It showed an edema suppression rate of ~30%. The method for synthesizing each compound will be explained below. Synthesis of compounds: Compounds can be synthesized by a so-called chloromethylation reaction. That is, as shown in the reaction formula below, (3,3,3-trifluoropropyl)
The compound is synthesized by reacting benzene, paraformaldehyde, and hydrogen chloride in the presence of zinc chloride. An example of a reaction process is shown. Paraformaldehyde and zinc chloride are suspended in (3,3,3-trifluoropropyl)benzene, and hydrogen chloride gas is blown into the suspension with vigorous stirring at a temperature of 40 to 80°C. The reaction proceeds smoothly by adding paraformaldehyde in several portions. Furthermore, as water by-produces as the reaction progresses, it dissolves zinc chloride and settles to the lower layer, so it is preferable to draw out this zinc chloride solution and replenish fresh zinc chloride at any time. (3, 3, 3
- Trifluoropropyl)benzene conversion rate to 90
It usually takes 10 to 30 hours to increase the amount to more than %. The progress of the reaction can be monitored by gas chromatography. After the reaction is completed, the reaction mixture is transferred to a separating funnel, and the lower layer (zinc chloride aqueous solution) is separated and removed. Ether was added to the upper organic layer and washed sequentially with water, 5% aqueous sodium bicarbonate solution, and water.
After drying with calcium chloride, the ether is distilled off to obtain a reaction mixture. Next, a compound is obtained by distilling the obtained reaction mixture. Synthesis of compound: The compound can be easily synthesized by reacting the compound with potassium cyanide or sodium cyanide in DMSO (Dimethyl Sulfoxide) as shown in the reaction formula below. The reaction temperature is preferably 40 to 50℃, and the reaction time is usually
The reaction time is 20 to 30 hours, and the progress of the reaction can be monitored by gas chromatography. After the reaction is complete, the reaction mixture is poured into excess water and then extracted with ether.
Next, the ether layer is washed with water, dried over calcium chloride, and then the ether is distilled off. The compound is obtained by distilling the reaction mixture thus obtained.
If necessary, the compound can be further purified by recrystallization from a chloroform-n-hexane mixed solvent. Synthesis of compound: The compound can be obtained by dissolving the compound in alcohol, adding a hydroalcoholic solution of potassium hydroxide to the solution, and heating under reflux conditions for 1 to 5 hours. After the reaction is completed, the solvent is distilled off, and then the compound is dissolved in water, the aqueous solution is washed with benzene, and the aqueous layer is made acidic by adding dilute hydrochloric acid to precipitate the compound as crystals. Further purification may be achieved by recrystallization from aqueous 70% ethanol. Hereinafter, the present invention will be explained in more detail based on Examples. However, the present invention is not limited to the following examples. Example 1 530 g (3.05 M) of (3,3,3-trifluoropropyl)benzene was added to a 2 capacity round bottom flask equipped with a stirrer and a reflux condenser.
28 g (0.94 M) of paraformaldehyde and 22.5 g (0.17 M) of zinc chloride were charged, and hydrogen chloride gas was blown into the flask while stirring vigorously at 60°C. The temperature inside the reaction system rose to 72°C. Paraformaldehyde is
After-charging was carried out four times with 28 g each (total 140 g), and zinc chloride was after-charged three times with 22.5 g each. In addition, the aqueous zinc chloride solution that separated during the reaction was once removed. The reaction was carried out for a total of 22.5 hours.
After the reaction was completed, the zinc chloride aqueous solution was separated, ether was added to the organic layer, and the organic layer was washed with water, 5% sodium bicarbonate aqueous solution, and water in this order, and after drying with calcium chloride, the ether was distilled off. 647 g of reaction mixture was obtained. This reaction mixture was analyzed using gas chromatography and gas chromatography mass spectrometry, and the results shown in Table 1 were obtained.
【表】
次いで、この反応混合物を蒸留して沸点74℃／
1.5mmHgの留分26.5ｇを得た。この留分は第１表
に於けるピークＢに相当するものであり、以下に
示す分析結果によりｐ−（３，３，３−トリフル
オロプロピル）ベンジルクロライドであることが
判明した。
(a) 質量分析 （20eV） ｍ／ｅ＝222
第１図にスペクトルを示す。
(b) 1H−NMR（60MHz CCl4溶液 TMS基準）
δ7.33ppm（ｄ、2H：Hb、Ｊ＝8Hz）
7.13 （ｄ、2H：Ha、Ｊ＝8Hz）
4.50 （ｓ、2H：Ar−ＣＨ 2−Ｃ）
1.9〜3.1 （ｍ、4H：−ＣＨ 2CＨ 2CF3）
第２図にスペクトルを示す。
(c) 赤外線吸収スペクトル
第３図にスペクトルを示す。
実施例 ２
容量500mlの丸底フラスコに化合物62.2ｇ
（0.28M）、シアン化カリウム20.8ｇ（0.31M）及
びDMSO150mlを入れて撹拌しながら40〜50℃で
22時間反応させた。反応終了後400mlの水に注ぎ、
エーテルで抽出した。エーテル層を水洗し、塩化
カルシウムで乾燥後にエーテルを留去した。次
に、減圧下にて蒸留して沸点109〜111℃の留分
32.5ｇを得た。この留分は結晶化したので一部を
クロロホルム−ｎ−ヘキサンから再結晶し、融点
37〜38℃の針状晶を得た。得られた針状晶の化合
物は、以下に示す分析結果より化合物であるこ
とが判明した。
(a) 質量分析 （20eV） ｍ／ｅ＝213
第４図にスペクトルを示す。
(b) 1H−NMR（60MHz CCl4溶液 TMS基準）
δ7.25ppm（ｓ、4H：Ar−Ｈ）
3.63 （ｓ、2H：Ar−ＣＨ 2CN）
1.9〜3.1 （ｍ、4H：−ＣＨ 2CＨ 2CF3）
第５図にスペクトルを示す。
(c) 赤外線吸収スペクトル
第６図にスペクトルを示す。
実施例 ３
化合物3.04ｇ（0.143M）を150mlのエタノー
ルに溶解し、これに水酸化カリウム28.7ｇ
（0.513M）を50％エタノール50mlに溶解したもの
を加えて３時間加熱還流させた。反応終了後に溶
媒を留去し、得られた残渣に水300mlを加えて溶
解し、次に200mlのベンゼンで２回洗滌した。次
に、水層に稀塩酸を加えて水層を酸性にしたとこ
ろ結晶が析出したのでこれを別し、70％エタノ
ールで再結晶して融点103〜104℃の鱗片状結晶19
ｇを得た。得られた結晶は、以下に示す分析結果
により化合物であることが判明した。
(a) 質量分析 （20eV） ｍ／ｅ＝232
第７図にスペクトルを示す。
(b) 1H−NMR（60MHz CCl4溶液、TMS基準）
δ12.1ppm（ｓ、1H：−COOＨ）
7.22 （ｓ、4H：Ar.−Ｈ）
3.61 （ｓ、2H：Ar.−ＣＨ 2−
COOH）
2.0〜3.1 （ｍ、4H：−ＣＨ 2CＨ 2CF3）
第８図にスペクトルを示す。
(c) 赤外線吸収スペクトル
番９図にスペクトルを示す。[Table] Next, this reaction mixture was distilled to a boiling point of 74℃/
26.5 g of a 1.5 mmHg fraction was obtained. This fraction corresponds to peak B in Table 1, and was found to be p-(3,3,3-trifluoropropyl)benzyl chloride by the analysis results shown below. (a) Mass spectrometry (20eV) m/e=222 Figure 1 shows the spectrum. (b) 1 H-NMR (60MHz CCl 4 solution TMS standard) δ7.33ppm (d, 2H: Hb, J = 8Hz) 7.13 (d, 2H: Ha, J = 8Hz) 4.50 (s, 2H: Ar-C H 2 −C) 1.9 to 3.1 (m, 4H: −CH 2 C H 2 CF 3 ) Figure 2 shows the spectrum. (c) Infrared absorption spectrum The spectrum is shown in Figure 3. Example 2 62.2g of compound in a 500ml round bottom flask
(0.28M), potassium cyanide 20.8g (0.31M) and DMSO 150ml and heated at 40-50℃ while stirring.
The reaction was allowed to proceed for 22 hours. After the reaction is complete, pour into 400ml of water.
Extracted with ether. The ether layer was washed with water, dried over calcium chloride, and then the ether was distilled off. Next, distill under reduced pressure to extract a fraction with a boiling point of 109 to 111℃.
32.5g was obtained. Since this fraction crystallized, a portion was recrystallized from chloroform-n-hexane to obtain a melting point of
Needle crystals at 37-38°C were obtained. The obtained needle-like compound was found to be a compound from the analysis results shown below. (a) Mass spectrometry (20eV) m/e=213 Figure 4 shows the spectrum. (b) 1 H-NMR (60MHz CCl 4 solution TMS standard) δ7.25ppm (s, 4H: Ar-H) 3.63 (s, 2H: Ar-C H 2 CN) 1.9-3.1 (m, 4H:-C H 2 C H 2 CF 3 ) The spectrum is shown in FIG. (c) Infrared absorption spectrum The spectrum is shown in Figure 6. Example 3 3.04 g (0.143 M) of the compound was dissolved in 150 ml of ethanol, and 28.7 g of potassium hydroxide was added to it.
(0.513M) dissolved in 50ml of 50% ethanol was added and heated under reflux for 3 hours. After the reaction was completed, the solvent was distilled off, and the resulting residue was dissolved in 300 ml of water, and then washed twice with 200 ml of benzene. Next, dilute hydrochloric acid was added to the aqueous layer to make it acidic, and crystals precipitated, which were separated and recrystallized with 70% ethanol to give scaly crystals with a melting point of 103-104℃.
I got g. The obtained crystals were found to be a compound based on the analysis results shown below. (a) Mass spectrometry (20eV) m/e=232 Figure 7 shows the spectrum. (b) 1H -NMR (60MHz CCl4 solution, TMS standard) δ12.1ppm (s, 1H:-COOH ) 7.22 (s, 4H:Ar.-H) 3.61 (s, 2H:Ar.- CH 2 −
COOH) 2.0-3.1 (m, 4H : -CH2CH2CF3 ) The spectrum is shown in FIG . (c) Infrared absorption spectrum Figure 9 shows the spectrum.
第１図は化合物の質量分析スペクトルを示
し、第２図は化合物のNMRスペクトルを示
し、第３図は化合物の赤外線吸収スペクトルを
示し、第４図は化合物の質量分析スペクトルを
示し、第５図は化合物のNMRスペクトルを示
し、第６図は化合物の赤外線吸収スペクトルを
示し、第７図は化合物の質量分析スペクトルを
示し、第８図は化合物のNMRスペクトルを示
し、第９図は化合物の赤外線吸収スペクトルを
示す図である。
Figure 1 shows the mass spectrometry spectrum of the compound, Figure 2 shows the NMR spectrum of the compound, Figure 3 shows the infrared absorption spectrum of the compound, Figure 4 shows the mass spectrometry spectrum of the compound, and Figure 5 shows the mass spectrometry spectrum of the compound. shows the NMR spectrum of the compound, Figure 6 shows the infrared absorption spectrum of the compound, Figure 7 shows the mass spectrometry spectrum of the compound, Figure 8 shows the NMR spectrum of the compound, and Figure 9 shows the infrared absorption spectrum of the compound. It is a figure showing an absorption spectrum.
Claims (1)
ピル）フエニル酢酸。 ２ （３，３，３−トリフルオロプロピル）ベン
ゼンをクロロメチル化して生成した（３，３，３
−トリフルオロプロピル）ベンジルクロライドを
精製してｐ−（３，３，３−トリフルオロプロピ
ル）ベンジルクロライドを得、得られたｐ−（３，
３，３−トリフルオロプロピル）ベンジルクロラ
イドのクロル基をシアノ基に変換してｐ−（３，
３，３−トリフルオロプロピル）ベンジルニトリ
ルを得、得られたｐ−（３，３，３−トリフルオ
ロプロピル）ベンジルニトリルを加水分解してｐ
−（３，３，３−トリフルオロプロピル）フエニ
ル酢酸を生成することを特徴とするｐ−（３，３，
３−トリフルオロプロピル）フエニル酢酸の製造
方法。[Claims] 1 formula p-(3,3,3-trifluoropropyl)phenylacetic acid represented by p-(3,3,3-trifluoropropyl)phenylacetic acid. 2 Produced by chloromethylation of (3,3,3-trifluoropropyl)benzene (3,3,3
-trifluoropropyl)benzyl chloride to obtain p-(3,3,3-trifluoropropyl)benzyl chloride, and the resulting p-(3,
The chloro group of 3,3-trifluoropropyl)benzyl chloride is converted to a cyano group to form p-(3,
3,3-trifluoropropyl)benzylnitrile was obtained, and the obtained p-(3,3,3-trifluoropropyl)benzylnitrile was hydrolyzed to give p-
-(3,3,3-trifluoropropyl)phenylacetic acid
A method for producing 3-trifluoropropyl)phenylacetic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15606481A JPS5857325A (en) | 1981-09-30 | 1981-09-30 | P-(3,3,3-trifluoropropyl)benzyl derivative and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15606481A JPS5857325A (en) | 1981-09-30 | 1981-09-30 | P-(3,3,3-trifluoropropyl)benzyl derivative and its production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5857325A JPS5857325A (en) | 1983-04-05 |
| JPH0155260B2 true JPH0155260B2 (en) | 1989-11-22 |
Family
ID=15619510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15606481A Granted JPS5857325A (en) | 1981-09-30 | 1981-09-30 | P-(3,3,3-trifluoropropyl)benzyl derivative and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5857325A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004007407A2 (en) | 2002-07-11 | 2004-01-22 | Fluorous Technologies Incorporated | Fluorous tagging and scavenging reactants and methods of synthesis and use thereof |
-
1981
- 1981-09-30 JP JP15606481A patent/JPS5857325A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5857325A (en) | 1983-04-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR880000688B1 (en) | Process for the preparation of leukotriene antagonists | |
| AU660854B2 (en) | New arylalkyl (thio)amides, process for preparing them and pharmaceutical compositions containing them | |
| JP3145824B2 (en) | Novel 2-cyano-3-hydroxyenamides, their preparation, pharmaceutical compositions containing them and their use as medicaments | |
| JPS6252742B2 (en) | ||
| JP2594855B2 (en) | Novel 3-cycloalkylpropanamides, their tautomeric forms and salts, their preparation, use as medicaments and compositions containing them | |
| JPH0717595B2 (en) | PHENOL DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND PHARMACEUTICAL COMPOSITION HAVING ANTIESTROGEN EFFECT CONTAINING THE COMPOUND | |
| JPH0742290B2 (en) | Method for aroylating 5-position of 1,2-dihydro-3H-pyrrolo [1,2-α] pyrrole-1-carboxylic acid ester | |
| EP0000200A1 (en) | New N-amidino-3,5-diamino-6-substituted-2-pyrazinecarboxamides and process for preparing same | |
| JPH032134B2 (en) | ||
| JPS58116434A (en) | Substituted phenoxyalkanol amines and phenoxyalkanol-cycloalkylamines | |
| JPS63145286A (en) | Bicyclic imidazole derivative | |
| JPH0559117B2 (en) | ||
| JPH0455427B2 (en) | ||
| JPH0231075B2 (en) | ||
| JPH0475224B2 (en) | ||
| JPH07215952A (en) | Catechol derivative | |
| US3860652A (en) | 8-Aminoalkyl substituted dibenzobicyclo {8 3.2.1{9 {0 octadienes | |
| JPS6127977A (en) | 4,5-dihydro-3,3-diphenyl-4-hydrocarbyl aminomethylfuran-2(3h)-one | |
| JP2894804B2 (en) | 2-Amino-5-methylbenzophenones and their production | |
| JP3771334B2 (en) | Preparation of 2-methyl-3- (3,4-methylenedioxyphenyl) acrylaldehyde | |
| JPH0338268B2 (en) | ||
| FR2602228A1 (en) | New phenoxyisobutyric acids, their derivatives and processes for producing them | |
| JPH0520425B2 (en) | ||
| JPS5857325A (en) | P-(3,3,3-trifluoropropyl)benzyl derivative and its production | |
| JPH053859B2 (en) |