JPS6351132B2 - - Google Patents
Info
- Publication number
- JPS6351132B2 JPS6351132B2 JP7368380A JP7368380A JPS6351132B2 JP S6351132 B2 JPS6351132 B2 JP S6351132B2 JP 7368380 A JP7368380 A JP 7368380A JP 7368380 A JP7368380 A JP 7368380A JP S6351132 B2 JPS6351132 B2 JP S6351132B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- compound
- formula
- propanol
- chloro
- 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
- 150000001875 compounds Chemical class 0.000 claims description 23
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- -1 3-(2-bromo-4-t-butylphenyl)-1-chloro-2-propanol Chemical compound 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 150000003944 halohydrins Chemical class 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEELDJDMRQTFIE-UHFFFAOYSA-N 5-[(2-bromophenyl)methyl]-1,3-oxazolidin-2-one Chemical compound BrC1=CC=CC=C1CC1OC(=O)NC1 WEELDJDMRQTFIE-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000010446 mirabilite Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- NHPSPBCFRKSRRT-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-3-chloropropan-2-ol Chemical compound CC(C)(C)C1=CC=C(CC(O)CCl)C=C1 NHPSPBCFRKSRRT-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 150000004996 alkyl benzenes Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 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 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- XRTANKYQJQXSFP-UHFFFAOYSA-N 1-tert-butyl-4-chlorobenzene Chemical compound CC(C)(C)C1=CC=C(Cl)C=C1 XRTANKYQJQXSFP-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- LVFFFZMLLZHVNL-UHFFFAOYSA-N 2-prop-2-enylaniline Chemical compound NC1=CC=CC=C1CC=C LVFFFZMLLZHVNL-UHFFFAOYSA-N 0.000 description 1
- OZRCRKRCXVINDF-UHFFFAOYSA-N 5-[(3-bromophenyl)methyl]-2H-1,3-oxazol-2-id-4-one Chemical compound BrC=1C=C(CC2C(N=[C-]O2)=O)C=CC=1 OZRCRKRCXVINDF-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- TWJVNKMWXNTSAP-UHFFFAOYSA-N azanium;hydroxide;hydrochloride Chemical compound [NH4+].O.[Cl-] TWJVNKMWXNTSAP-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229930015698 phenylpropene Natural products 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- HJWLCRVIBGQPNF-UHFFFAOYSA-N prop-2-enylbenzene Chemical compound C=CCC1=CC=CC=C1 HJWLCRVIBGQPNF-UHFFFAOYSA-N 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は医薬の合成中間体として有用な一般式
（）
（式中、Ｘはハロゲン原子を、Ｒは水素原子あ
るいはｔ―ブチル基を示す）
で表わされるハロヒドリン誘導体ならびにその製
造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention provides the general formula () useful as a synthetic intermediate for pharmaceuticals. (In the formula, X represents a halogen atom and R represents a hydrogen atom or a t-butyl group.) The present invention relates to a halohydrin derivative represented by the following formula and a method for producing the same.
上記一般式（）で表わされる本発明化合物
は、筋弛緩、鎮痛並びに、抗炎症作用を有し、筋
硬直およびこれに伴う疼痛、炎症、ならびに脳卒
中患者の後遺症である筋硬直や他の筋硬直に対す
るリハビリテーシヨン等の治療薬として使用でき
る５―（ｏ―ブロモベンジル）―２―オキサゾリ
ドン（特公昭59−28552）の合成中間体として用
いられる。 The compound of the present invention represented by the above general formula () has muscle relaxing, analgesic, and anti-inflammatory effects, and is effective against muscle stiffness, associated pain, inflammation, and muscle stiffness and other muscle stiffness that are sequelae of stroke patients. It is used as an intermediate for the synthesis of 5-(o-bromobenzyl)-2-oxazolidone (Japanese Patent Publication No. 59-28552), which can be used as a therapeutic drug for rehabilitation and the like.
従来、（５―ブロモベンジル）―２―オキサゾ
リドンを得る合成方法としては上記特許公報等に
記載のｏ―ブロモアリルベンゼンを経由して例え
ば以下の方法等により得られていた。 Conventionally, (5-bromobenzyl)-2-oxazolidone has been synthesized via o-bromoallylbenzene described in the above-mentioned patent publications, for example, by the following method.
一般的にアリルベンゼンのベンゼン核のオルト
位に選択的にハロゲン（臭素）を入れることは難
しく、パラ異性体の生成、アリル基のハロゲン化
を伴い、更にこれらの各異性体からの分離も難し
く、工業上望ましい方法ではない。一方、公知の
ｏ―アリルアニリンからサンドマイヤー反応をも
ちいてｏ―ブロモアリルベンゼンを得る上記の方
法では、２―アリルアニリンに臭素を入れる際、
高価なCuBrを用いる点や危険なジアゾ体を経由
すること等の問題があつた。更にこのｏ―ブロモ
アリルベンゼンから目的物である５―（ｏ―ブロ
モベンジル）―２―オキサゾリドンを得るのにア
リル基を酸化してエポキシ体を得ているがこの工
程も同様に酸化剤が高価であり危険であること等
の理由により工業上満足できるもではなかつた。 Generally, it is difficult to selectively insert halogen (bromine) into the ortho position of the benzene nucleus of allylbenzene, which involves the formation of para isomers and halogenation of the allyl group, and furthermore, it is difficult to separate from each of these isomers. , which is not an industrially desirable method. On the other hand, in the above-mentioned method for obtaining o-bromoallylbenzene from known o-allylaniline using the Sandmeyer reaction, when adding bromine to 2-allylaniline,
There were problems such as the use of expensive CuBr and the use of dangerous diazo compounds. Furthermore, to obtain the target product 5-(o-bromobenzyl)-2-oxazolidone from this o-bromoallylbenzene, the allyl group is oxidized to obtain an epoxy compound, but the oxidizing agent is also expensive in this process. This was not industrially satisfactory for reasons such as being dangerous.
本発明は、上記一般式（）で表わされる本発
明化合物を、合成中間体として経由することによ
り、これらの点が改良され、しかも簡便に目的化
合物である５―（ｏ―ブロモベンジル）―２―オ
キサゾリドンを得ることのできることを見い出し
本発明を完成した。 The present invention improves these points by using the compound of the present invention represented by the above general formula () as a synthetic intermediate, and moreover, the target compound 5-(o-bromobenzyl)-2 can be easily synthesized. -We have discovered that oxazolidone can be obtained and completed the present invention.
従つて本発明は医薬の合成中間体として有用な
一般式（）で表わされる新規化合物を提供せん
とするにある。 Therefore, it is an object of the present invention to provide a novel compound represented by the general formula () which is useful as a synthetic intermediate for pharmaceuticals.
他の目的は、一般式（）で表わされる化合物
を製造するための方法を提供せんとするにある。 Another object is to provide a method for producing a compound represented by the general formula ().
本発明の一般式（）の化合物は次の如くして
製造される。 The compound of general formula () of the present invention is produced as follows.
（式中、Ｘは前記と同じ）
すなわち、一般式（）で表わされる化合物に
臭素を反応させることにより、一般式（）′の
化合物が製造され、所望によりｔ―ブチル基を脱
離せしめることにより一般式（）″の化合物が
製造される。 (In the formula, X is the same as above) That is, by reacting the compound represented by the general formula () with bromine, the compound of the general formula ()' is produced, and if desired, the t-butyl group is eliminated. A compound of general formula ()'' is produced by
一般式（）′の化合物を得るには、一般式
（）の化合物の水溶液中に臭素を滴下せしめる
ことにより行なわれる。反応は、室温にて１〜４
時間で完了する。 The compound of general formula ()' can be obtained by dropping bromine into an aqueous solution of the compound of general formula (). The reaction is carried out at room temperature between 1 and 4.
Complete in time.
また、所望によりｔ―ブチル基を脱離せしめて
一般式（）″の化合物を得るには、一般に有機
溶媒中で塩化アルミニウムと反応させることによ
り行なわれる。溶媒は、トルエン、ベンゼン等が
好ましく室温にて３〜10時間反応させるのが好ま
しい。 Further, if desired, the t-butyl group can be eliminated to obtain a compound of the general formula ()'', which is generally carried out by reaction with aluminum chloride in an organic solvent.The solvent is preferably toluene, benzene, etc. It is preferable to react for 3 to 10 hours.
尚、原料である一般式（）の化合物は、４―
ｔ―ブチルハロゲノベンゼンにマグネシウムを反
応させて、グリニヤール試薬とし、これにエピク
ロルヒドリンなどのエピハロゲノヒドリンを反応
させることにより製造される。 In addition, the compound of general formula () which is a raw material is 4-
It is produced by reacting t-butylhalogenobenzene with magnesium to obtain a Grignard reagent, and reacting this with an epihalogenohydrin such as epichlorohydrin.
本発明の一般式（）の化合物、殊に一般式
（）″で表わされる化合物は、例えばシアン酸カ
リウムと有機溶媒中で反応させることにより、消
炎、鎮痛および筋弛緩剤として有用な、５―（ｏ
―ブロモベンジル）オキサゾリドンに変換せしめ
ることができる。 The compounds of the general formula () of the present invention, especially the compounds represented by the general formula ()'', can be prepared by reacting with potassium cyanate in an organic solvent to produce a 5- (o
-bromobenzyl)oxazolidone.
一般式（）″で表される本発明化合物から５
―（ｏ―ブロモベンジル）―２―オキサゾリドン
に至る合成ルートを次に示す。 5 from the compound of the present invention represented by the general formula ()''
The synthetic route to -(o-bromobenzyl)-2-oxazolidone is shown below.
一般的にアルキルベンゼンをハロゲン化（臭素
化）して選択的にオルト位にハロゲン（臭素）を
入れることは難しく、また従来方法は高価な試
薬、危険な試薬等を用いており、工業的に満足で
きるものではなかつたが、本発明化合物を経由す
ることでこれらの点が改良され、更にアルキルベ
ンゼンの４位をｔ―ブチル基で保護することによ
り、安価で取り扱いやすい臭素を用いて、臭素を
オルト位に収率よく導入できる。 Generally, it is difficult to halogenate (bromine) alkylbenzene to selectively introduce halogen (bromine) into the ortho position, and conventional methods use expensive and dangerous reagents, making them industrially unsatisfactory. However, by using the compound of the present invention, these points have been improved, and by protecting the 4-position of the alkylbenzene with a t-butyl group, bromine can be converted into ortho can be introduced with good yield.
かくして得られた一般式（）で表わされる本
発明化合物に例えばアルカリで処理することによ
りきわめて簡便にエポキシ体を得ることができそ
してこれをさらに尿素等で処理することにより目
的物である５―（ｏ―ブロモベンジル）―２―オ
キサゾリドンを得ることができる。 By treating the thus obtained compound of the present invention represented by the general formula () with, for example, an alkali, an epoxy compound can be obtained very easily, and by further treating this with urea etc., the desired compound 5-( o-bromobenzyl)-2-oxazolidone can be obtained.
次に、参考例および実施例を挙げて本発明を詳
細に説明する。 Next, the present invention will be explained in detail with reference to reference examples and examples.
参考例
３―（４―ｔ―ブチルフエニル）―１―クロロ
―２―プロパノールの製造：
500ml４ツ口フラスコに磁性回転子を入れ、還
流管、200ml滴下ロートおよび窒素球を取りつけ
た。次にグリニヤール反応用金属マグネシウム
16.9ｇ、無水テトラヒドロフラン10ｇ、触媒量の
ヨウ素およびヨウ化メチルを加え室温にて約10分
間撹拌した。ヨウ素の色が消え、反応が開始した
ら反応容器をあらかじめ90〜100゜に加温した油浴
に浸し、４―ｔ―ブチルクロロベンゼン90ｇのテ
トラヒドロフラン106ｇ溶液を還流下、約75分で
滴下した。この時マグネシウムは徐々に溶解し、
内温は92゜まで上昇した。滴下終了後、さらに２
時間撹拌した。ガスクロマトグラフイーにて、グ
リニヤール試薬の生成を確認した。水浴にて内温
50゜まで冷却し、エピクロルヒドリン99.0ｇを約
30分で滴下した。滴下終了後、水浴をはずし、さ
らに30分間撹拌を行なつた。反応混合物を冷却し
た10％塩化アンモニウム水１中に注ぎ、酢酸エ
チル１で抽出した。酢酸エチル層を飽和食塩水
１にて２度洗浄後、芒硝乾燥した。芒硝を
別、酢酸エチルを留去し、残留物の減圧蒸留にて
３―（４―ｔ―ブチルフエニル）―１―クロロ―
２―プロパノール88.2ｇを得た。（沸点122〜
126゜／２mmＨｇ、純度96.7％、収率70.7％）
なお、４―ｔ―ブチルプロモペンゼンを原料と
しても上記同様にして３―（４―ｔ―ブチルフエ
ニル）―１―クロロ―２―プロパノールが得られ
た。Reference Example 3 - Production of (4-t-butylphenyl)-1-chloro-2-propanol: A magnetic rotor was placed in a 500ml four-necked flask, and a reflux tube, a 200ml dropping funnel, and a nitrogen bulb were attached. Next, metallic magnesium for Grignard reaction.
16.9 g of anhydrous tetrahydrofuran, 10 g of anhydrous tetrahydrofuran, catalytic amounts of iodine and methyl iodide were added, and the mixture was stirred at room temperature for about 10 minutes. When the color of iodine disappeared and the reaction started, the reaction vessel was immersed in an oil bath preheated to 90-100°, and a solution of 90 g of 4-t-butylchlorobenzene in 106 g of tetrahydrofuran was added dropwise under reflux over about 75 minutes. At this time, magnesium gradually dissolves,
The internal temperature rose to 92°. After dropping, add 2 more
Stir for hours. Generation of Grignard reagent was confirmed by gas chromatography. Internal temperature in water bath
Cool to 50° and add 99.0g of epichlorohydrin to approx.
It was dripped in 30 minutes. After the dropwise addition was completed, the water bath was removed and stirring was continued for an additional 30 minutes. The reaction mixture was poured into 1 portion of cooled 10% ammonium chloride water and extracted with 1 portion of ethyl acetate. The ethyl acetate layer was washed twice with saturated brine 1 and then dried over sodium sulfate. Separate the Glauber's salt, distill off the ethyl acetate, and distill the residue under reduced pressure to obtain 3-(4-t-butylphenyl)-1-chloro-
88.2 g of 2-propanol was obtained. (boiling point 122~
(126°/2 mmHg, purity 96.7%, yield 70.7%) In addition, 3-(4-t-butylphenyl)-1-chloro-2-propanol was produced in the same manner as above using 4-t-butylpromopenzene as a raw material. Obtained.
実施例 １
３―（２―ブロモ―４―ｔ―ブチルフエニル）
―１―クロロ―２―プロパノール：
３―（４―ｔ―ブチルフエニル）―１―クロロ
―２―プロパノール27.0ｇに水135mlを加えて、
激しく撹拌しながら臭素12.4mlを約30分で滴下し
た。滴下終了後さらに室温にて２時間撹拌を続け
た。反応混合物を亜硫酸ナトリウム60ｇを溶かし
た氷水500ml中に注いだ。これをトルエンにて抽
出し、飽和亜硫酸ナトリウム水溶液、飽和炭酸ナ
トリウム水溶液、水（３回）の順で洗浄し、芒硝
乾燥した。溶媒を減圧下に留去して、沸点153〜
155゜／12.0mmＨｇの３―（２―ブロモ―４―ｔ―
ブチルフエニル）―１―クロロ―２―プロパノー
ル42.3ｇを得た。Example 1 3-(2-bromo-4-t-butylphenyl)
-1-Chloro-2-propanol: Add 135 ml of water to 27.0 g of 3-(4-t-butylphenyl)-1-chloro-2-propanol,
While stirring vigorously, 12.4 ml of bromine was added dropwise over about 30 minutes. After the dropwise addition was completed, stirring was continued for 2 hours at room temperature. The reaction mixture was poured into 500 ml of ice water containing 60 g of sodium sulfite. This was extracted with toluene, washed in this order with a saturated aqueous sodium sulfite solution, a saturated aqueous sodium carbonate solution, and water (3 times), and dried with mirabilite. The solvent was distilled off under reduced pressure and the boiling point was 153~
3-(2-bromo-4-t-) of 155°/12.0mmHg
42.3 g of (butylphenyl)-1-chloro-2-propanol was obtained.
IRνCHCl3 naxcm-1：3600，3020，2960
NMR（CCl4）δ：1.28（9H，ｓ，―CH3×３）
2.80〜3.10（3H，ｍ，―OH，ψ―CH2）
3.40〜3.60（2H，ｍ，CH2Cl）
3.90〜4.20（1H，ｍ，CH―Ｏ―）
7.22，7.50（3H，each ｓ，芳香族プロト
ン）
実施例 ２
３―（２―ブロモフエニル）―１―クロロ―２
―プロパノール：
３―（２―ブロモ―４―ｔ―ブチルフエニル）
―１―クロロ―２―プロパノール42ｇのトルエン
500ml溶液に、無水塩化アルミニウム30.6ｇを加
え、室温にて１時間激しく撹拌した。さらに、無
水塩化アルミニウム3.2ｇを追加し、3.5時間撹拌
した。反応終了後、反応液を氷水１中に注ぎ、
よくかきまぜた。水層を除去し、トルエン層を10
％炭酸ナトリウム水溶液で洗浄し、芒硝乾燥し
た。溶媒を減圧下に留去し、３―（２―ブロモフ
エニル）―１―クロロ―２―プロパノール27.4ｇ
（沸点118〜120゜／2.5mmＨｇ）を得た。 IRν CHCl3 nax cm -1 : 3600, 3020, 2960 NMR (CCl 4 ) δ: 1.28 (9H, s, -CH 3 ×3) 2.80 to 3.10 (3H, m, -OH, ψ - CH 2 ) 3.40 to 3.60 (2H, m, CH 2 Cl) 3.90-4.20 (1H, m, CH-O-) 7.22, 7.50 (3H, each s, aromatic proton) Example 2 3-(2-bromophenyl)-1-chloro- 2
-Propanol: 3-(2-bromo-4-t-butylphenyl)
-1-chloro-2-propanol 42g toluene
30.6 g of anhydrous aluminum chloride was added to the 500 ml solution, and the mixture was vigorously stirred at room temperature for 1 hour. Furthermore, 3.2 g of anhydrous aluminum chloride was added and stirred for 3.5 hours. After the reaction is complete, pour the reaction solution into ice water 1,
Stir well. Remove the aqueous layer and remove the toluene layer for 10 min.
% aqueous sodium carbonate solution and dried over Glauber's salt. The solvent was distilled off under reduced pressure, and 27.4 g of 3-(2-bromophenyl)-1-chloro-2-propanol was obtained.
(boiling point 118-120°/2.5 mmHg) was obtained.
IRνneat naxcm-1：3400，2950 NMR（CCl4）δ：2.60（1H，b.s，OH） 2.70〜3.10（2H，ｍ，ψ―CH2） 3.30〜3.68（2H，ｍ，―CH2Cl） 3.80〜4.20（1H，ｍ，CH―Ｏ―） 6.98〜7.64（4H，ｍ，芳香族プロトン）。 IRν neat nax cm -1 : 3400, 2950 NMR (CCl 4 ) δ: 2.60 (1H, bs, OH) 2.70 to 3.10 (2H, m, ψ-CH 2 ) 3.30 to 3.68 (2H, m, -CH 2 Cl ) 3.80 to 4.20 (1H, m, CH—O—) 6.98 to 7.64 (4H, m, aromatic proton).
Claims (1)
るいはｔ―ブチル基を示す） で表わされるハロヒドリン誘導体。 ２ ３―（２―ブロモ―４―ｔ―ブチルフエニ
ル）―１―クロロ―２―プロパノールである特許
請求の範囲第１項記載のハロヒドリン誘導体。 ３ ３―（２―ブロモフエニル）―１―クロロ―
２―プロパノールである特許請求の範囲第１項記
載のハロヒドリン誘導体。 ４ 一般式 （式中、Ｘはハロゲン原子を示す） で表わされる化合物に臭素を反応させることを特
徴とする、一般式 （式中、Ｘは前記と同じ） で表わされるハロヒドリン誘導体の製造方法。 ５ 一般式 （式中、Ｘはハロゲン原子を示す） で表わされる化合物からｔ―ブチル基を脱離する
ことを特徴とする、一般式 （式中、Ｘは前記と同じ） で表わされるハロヒドリン誘導体の製造方法。[Claims] 1. General formula (In the formula, X represents a halogen atom, and R represents a hydrogen atom or a t-butyl group.) A halohydrin derivative represented by: 2. The halohydrin derivative according to claim 1, which is 3-(2-bromo-4-t-butylphenyl)-1-chloro-2-propanol. 3 3-(2-bromophenyl)-1-chloro-
The halohydrin derivative according to claim 1, which is 2-propanol. 4 General formula (In the formula, X represents a halogen atom) A general formula characterized by reacting bromine with a compound represented by (In the formula, X is the same as above.) A method for producing a halohydrin derivative represented by the following. 5 General formula (In the formula, X represents a halogen atom) A general formula characterized by removing a t-butyl group from a compound represented by (In the formula, X is the same as above.) A method for producing a halohydrin derivative represented by the following.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7368380A JPS56169635A (en) | 1980-06-03 | 1980-06-03 | Halohydrin derivative and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7368380A JPS56169635A (en) | 1980-06-03 | 1980-06-03 | Halohydrin derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS56169635A JPS56169635A (en) | 1981-12-26 |
| JPS6351132B2 true JPS6351132B2 (en) | 1988-10-13 |
Family
ID=13525253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7368380A Granted JPS56169635A (en) | 1980-06-03 | 1980-06-03 | Halohydrin derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS56169635A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107266306A (en) * | 2009-07-07 | 2017-10-20 | 拜耳知识产权有限责任公司 | Prepare（The base of 2,4 dimethyl diphenyl 3）The method of acetic acid, its ester and midbody compound |
-
1980
- 1980-06-03 JP JP7368380A patent/JPS56169635A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56169635A (en) | 1981-12-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4336648B2 (en) | Process for producing epoxytriazole derivative and its intermediate | |
| JPS6351132B2 (en) | ||
| JP4407062B2 (en) | Method for producing diphenyl disulfide derivative | |
| JPH0733684A (en) | 1-halo-cis-3-tetradecene and production of cis-olefin compound using the tetradecene compound | |
| JPH0115497B2 (en) | ||
| JP4902976B2 (en) | Fluorinated 1,3-benzodioxane, its preparation and use | |
| JP3771334B2 (en) | Preparation of 2-methyl-3- (3,4-methylenedioxyphenyl) acrylaldehyde | |
| EP0220792B1 (en) | A method for producing 2-aryl-propionaldehydes | |
| JP2003502300A (en) | Synthesis process of 1- (3,5-bis (trifluoromethyl) -phenyl) ethan-1-one | |
| JP4034040B2 (en) | Fluorine-containing diene compounds | |
| JPH0696564B2 (en) | α- (ω-hydroxyalkyl) furfuryl alcohol and process for producing the same | |
| JP4018816B2 (en) | Cycloheptenone derivative and method for producing the same, and method for producing cycloheptimidazole derivative using the same | |
| JP2002512210A (en) | Method for producing 2-hydroxyalkylhalophenone | |
| JPS5858335B2 (en) | Alpha - Chikanacetone no Seizouhou | |
| JPWO2004076459A1 (en) | Quaternary ammonium bifluoride compound and method for producing nitroalcohol using the same | |
| JPH0481981B2 (en) | ||
| JP2840849B2 (en) | Linear polyphosphine borane complex and method for producing the same, and phosphine boransulfonates and method for producing the same | |
| JPS6126893B2 (en) | ||
| JP3056360B2 (en) | Production method of γ-coronal | |
| EP0414686A1 (en) | Derivatives of trifluoromethyl-1-tetralines, preparation and application thereof for the synthesis of compounds having therapeutic properties. | |
| JPS6126894B2 (en) | ||
| JPH0753679B2 (en) | Process for producing 3-hydroxy-4-phenyl-2-butanone | |
| JPS5823868B2 (en) | Method for producing β↓-(β↓-chloroethylsulfonyl)propionic acid derivative | |
| JP2002212149A (en) | METHOD FOR PRODUCING TETRAALKYLAMMONIUM FLUORIDE AND METHOD FOR PRODUCING beta-HYDROXYKETONE BY USING THE SAME | |
| JPH0586770B2 (en) |