JPS62207235A - Production of isopropenyl ether or ester derivative - Google Patents
Production of isopropenyl ether or ester derivativeInfo
- Publication number
- JPS62207235A JPS62207235A JP5006886A JP5006886A JPS62207235A JP S62207235 A JPS62207235 A JP S62207235A JP 5006886 A JP5006886 A JP 5006886A JP 5006886 A JP5006886 A JP 5006886A JP S62207235 A JPS62207235 A JP S62207235A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- group
- expressed
- ether
- ester 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.)
- Pending
Links
- 150000002148 esters Chemical class 0.000 title claims abstract description 17
- FKTLISWEAOSVBS-UHFFFAOYSA-N 2-prop-1-en-2-yloxyprop-1-ene Chemical class CC(=C)OC(C)=C FKTLISWEAOSVBS-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims abstract description 10
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical class CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract 7
- 125000005843 halogen group Chemical group 0.000 claims abstract 3
- 238000003682 fluorination reaction Methods 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 10
- 150000002367 halogens Chemical class 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 239000013543 active substance Substances 0.000 abstract description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 abstract 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- -1 monofluoroisopropenyl ethers Chemical class 0.000 description 13
- 239000000047 product Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000002808 molecular sieve Substances 0.000 description 7
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical group [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 2
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940051269 1,3-dichloro-2-propanol Drugs 0.000 description 1
- DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 description 1
- PVDLUGWWIOGCNH-UHFFFAOYSA-N 1,3-difluoro-2-propanol Chemical compound FCC(O)CF PVDLUGWWIOGCNH-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- CCNWZGXOWHXIJE-UHFFFAOYSA-N ethoxyethane;oxane Chemical compound CCOCC.C1CCOCC1 CCNWZGXOWHXIJE-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- KNWQLFOXPQZGPX-UHFFFAOYSA-N methanesulfonyl fluoride Chemical compound CS(F)(=O)=O KNWQLFOXPQZGPX-UHFFFAOYSA-N 0.000 description 1
- MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 1
- QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
Landscapes
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Pyrane Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、種々の生理活性物質を製造するために用いる
中間体として有用なイソプロペニルエーテル又はエステ
ル誘導体の製造方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing isopropenyl ether or ester derivatives useful as intermediates for producing various physiologically active substances.
モノフルオロイソプロペニルエーテル及びエステルにつ
いては、これまでにベンジルエーテルの合成例のみが報
告されている。そして、この方法では１．３−ジフルオ
ロ−２−プロパツールを対応するアルコキシドに変化さ
せた後、ベンジルプロミドを用いてエーテル化し、さら
に塩基を用いてフッ化水素を脱離させて目的とするモノ
フルオロイソプロペニルエーテル誘導体を合成していた
。Regarding monofluoroisopropenyl ethers and esters, only a synthesis example of benzyl ether has been reported so far. In this method, 1,3-difluoro-2-propanol is converted into the corresponding alkoxide, then etherified using benzyl bromide, and then hydrogen fluoride is eliminated using a base to obtain the desired product. Monofluoroisopropenyl ether derivatives were being synthesized.
しかしながら、この方法では反応工程が多く煩雑である
うえ、適応範囲もアルキルエーテルに限られるという問
題がある。However, this method involves many reaction steps and is complicated, and the range of application is limited to alkyl ethers.
〔発明が解決しようとする問題点〕
従って、本発明は簡易な手段で、かつ高収率でイソプロ
ペニルエーテル及びエステルを製造する方法を提供する
ことを目的とする。[Problems to be Solved by the Invention] Therefore, an object of the present invention is to provide a method for producing isopropenyl ether and ester by simple means and in high yield.
本発明は、１．３位にハロゲン又はアルキルスルホニル
オキシ基を有するイソプロピルエーテル又はエステルに
第４級アンモニウムフルオリドを作用させると容易にオ
レフィン化とフッ素の導入ができ、上記問題点を有効に
解決できるとの知見に基づいてなされたのである。The present invention effectively solves the above problems by allowing quaternary ammonium fluoride to easily form an olefin and introduce fluorine into isopropyl ether or ester having a halogen or alkylsulfonyloxy group at the 1 and 3 positions. This was done based on the knowledge that it could be done.
すなわち、本発明は、一般式（Ｉ） ：Ｈ２Ｘ
■
（式中、Ｒ１は炭化水素基、複素環基又はキル基を示す
）であり、Ｘはハロゲン又はアルキルスルホニルオキシ
基を示す。）
で表わされるイソプロピルエーテル又はエステルｌ導体
に第４級アンモニウムフルオリドを作用させて、ＨＸ
（Ｘは上記と同じ意味を有する。）を脱離させることを
特徴とする一般式（■）＝（式中、Ｒ，とＸは上記と同
じ意味を有する。）で表わされるインプロペニルエーテ
ル又はエステル誘導体の製造方法、及び該生成物を第４
級アンモニウムフルオリドでフッ素化することを特徴と
する一般式（■）：
（式中、Ｒ，は上記と同じ意味を有する。）で表わされ
るイソプロペニルエーテル又はエステル誘導体の製造方
法を提供する。That is, the present invention is based on the general formula (I): H2X (wherein R1 represents a hydrocarbon group, a heterocyclic group, or a kyl group), and X represents a halogen or an alkylsulfonyloxy group. ) isopropyl ether or ester l conductor is treated with quaternary ammonium fluoride to form HX
Impropenyl ether represented by the general formula (■) = (wherein, R and A method for producing an ester derivative, and a fourth method for producing the product.
Provided is a method for producing an isopropenyl ether or ester derivative represented by the general formula (■): (wherein R has the same meaning as above), which is characterized by fluorination with ammonium fluoride.
本発明において出発原料として用いる一般式（１）で表
わされるイソプロピルエーテル誘導体、イソプロピルカ
ルバミン酸エステル誘導体は、例えば式（■）：
ｌｌ２Ｘ
で表わされるハロ炭酸エステルや式（Ｖ）：で表わされ
るスルホナートから容易に合成される。The isopropyl ether derivatives and isopropyl carbamate ester derivatives represented by the general formula (1) used as starting materials in the present invention are, for example, halocarbonate esters represented by the formula (■): ll2X and sulfonates represented by the formula (V): Easily synthesized.
又、式（１）中、Ｘがアルキルスルホニルオキシ基であ
る化合物は、Ｘが−ＯＨである対応する化合物にアルキ
ルスルホニルハライドなどを反応させて容易に合成され
る。Further, a compound in which X is an alkylsulfonyloxy group in formula (1) can be easily synthesized by reacting an alkylsulfonyl halide or the like with a corresponding compound in which X is -OH.
本発明においては、式（Ｉ）で表わされる化合物のうち
、式中のＲ１としては、炭素数１〜５０のアルキル基、
炭素数６〜１４の芳香族基、炭素数３〜１３の複素環基
が好ましく、特に好ましくは、フェニル基、ベンジル基
、ナフチル基、テトラヒドロピラニル基、α−エトキシ
エチル基が例示される。式中のＲ２及びＲ３としては炭
素数１〜５０のアルキル基が好ましい。又式中、Ｘとし
ては塩素及び臭素が好ましく、アルキルスルホニルオキ
シ基のアルキル基としては炭素数１〜７のものが好まし
い。In the present invention, among the compounds represented by formula (I), R1 in the formula is an alkyl group having 1 to 50 carbon atoms,
Aromatic groups having 6 to 14 carbon atoms and heterocyclic groups having 3 to 13 carbon atoms are preferred, with phenyl, benzyl, naphthyl, tetrahydropyranyl, and α-ethoxyethyl groups being particularly preferred. R2 and R3 in the formula are preferably alkyl groups having 1 to 50 carbon atoms. In the formula, X is preferably chlorine or bromine, and the alkyl group of the alkylsulfonyloxy group is preferably one having 1 to 7 carbon atoms.
本発明では上記化合物（Ｉ）に第４級アンモニウムフル
オリドを作用させて下記の反応を行なうのである。In the present invention, the following reaction is carried out by reacting the above compound (I) with quaternary ammonium fluoride.
ここで用いる第４級アンモニウムフルオリドとしては、
下記一般式（■）：
（式中、Ｒ１−Ｒ７は、炭素数１〜１６のアルキル基、
アルケニル基又は芳香族基を示す。）で表わされる第４
級アンモニウムフルオリドを用いるのが好ましい。上記
式（Ｖｌ）において、Ｒ４−Ｒ１は同一でも異なってい
てもよく、特にＲ４−Ｒ７は炭素数１〜１６のアルキル
基が好ましい。The quaternary ammonium fluoride used here is
The following general formula (■): (wherein, R1-R7 are an alkyl group having 1 to 16 carbon atoms,
Indicates an alkenyl group or an aromatic group. )
Preferably, grade ammonium fluoride is used. In the above formula (Vl), R4-R1 may be the same or different, and R4-R7 is particularly preferably an alkyl group having 1 to 16 carbon atoms.
又、式中芳香族基としてはフェニル基、ベンジル基など
が好ましい。上記第４級アンモニウム塩として、具体的
には、テトラ（ｎ−ブチル）アンモニウムフルオリド（
以下、ＴＢＡＦという）、テトラエチルアンモニウムフ
ルオリド、テトラメチルアンモニウムフルオリド、ペン
ジルトリメチルアンモニウムフルオリドが例示される。Further, as the aromatic group in the formula, phenyl group, benzyl group, etc. are preferable. Specifically, the quaternary ammonium salt mentioned above is tetra(n-butyl)ammonium fluoride (
(hereinafter referred to as TBAF), tetraethylammonium fluoride, tetramethylammonium fluoride, and penzyltrimethylammonium fluoride.
本発明では、上記第４級アンモニウム塩を、カルバミン
酸エステルに対して、１．０〜１０当量、好ましくは１
〜５当量の割合で存在させ、−１０〜５０℃の温度に３
〜４８時間加熱して上記の反応を行なうのである。さら
に、上記反応は、テトラヒドロ７ラン（ＴＨＦ）ジエチ
ルエーテル、１゜４−ジオキサンなどの不活性溶媒の下
で行なうことができ、又、モレキュラーシーブを共存さ
せることが望ましい。In the present invention, the quaternary ammonium salt is used in an amount of 1.0 to 10 equivalents, preferably 1 equivalent to the carbamate ester.
~5 equivalents and at a temperature of -10 to 50°C.
The above reaction is carried out by heating for ~48 hours. Further, the above reaction can be carried out in an inert solvent such as tetrahydrofane (THF) diethyl ether or 1°4-dioxane, and it is desirable to coexist a molecular sieve.
尚、上記反応において、一般式（ＩＩ）で表わされる化
合物を高収率で得るためには、反応を低温、例えば−１
Ｏ〜０℃で行なうのがよい。In the above reaction, in order to obtain the compound represented by general formula (II) in high yield, the reaction is carried out at a low temperature, for example -1
It is preferable to carry out the reaction at a temperature of 0 to 0°C.
本発明において上記反応を行なうに際し、一般式（Ｉ）
にふいてＸがアルキルスルホニルオキシ基である化合物
を用いる場合には、Ｘが−ＯＨである対応する化合物に
アルキルスルホニルハライド特に好ましくは炭素数１〜
７のアルキルスルホニルハライドを第４級アンモニウム
フルオリドとともに作用させることによって、対応する
化合物（■）及び（ＩＩＩ）を容易に製造することがで
きる。When carrying out the above reaction in the present invention, general formula (I)
When using a compound in which X is an alkylsulfonyloxy group, an alkylsulfonyl halide particularly preferably has 1 to 1 carbon atoms in the corresponding compound in which
By reacting the alkylsulfonyl halide of No. 7 with quaternary ammonium fluoride, the corresponding compounds (■) and (III) can be easily produced.
本発明によれば、１，３位にハロゲン又はアルキルスル
ホニルオキシ基を有するイソプロピルエーテル又はエス
テル誘導体から簡易な手段でかつ高収率でイソプロペニ
ルエーテル又はエステル誘導体を製造することができる
ので工業的な製法として極めてすぐれたものである。According to the present invention, isopropenyl ether or ester derivatives can be produced by simple means and in high yield from isopropyl ether or ester derivatives having halogen or alkylsulfonyloxy groups at the 1 and 3 positions, so that it can be produced industrially. This is an extremely excellent manufacturing method.
次に実施例により本発明を説明する。Next, the present invention will be explained with reference to Examples.
実施例１
ドライバツク中、３０ｍｊ！ナス型フラスコにテトラ（
ｎ−ブチル）アンモニウムフルオリド・３水和物５３１
ｍｇ （Ｔｈｘ３）、モレキュ５−シー１４ Ａ １．
０ ｇを入れ、さらに無水テトラヒドロフラン（ＴＨＦ
）５ｍｌを加えた後、窒素気流下室温で攪拌した。その
後、反応液を０℃に冷却し１．３−ジブロモ−２−プロ
ビルジイソプロピル力ルバメー） １９４ｍｇ （０，
５６２ｍモル）を加え、０℃で２時間攪拌した。次に、
反応液をシリカゲルで濾過し、モレキュラーシーブ４Ａ
を除去し、酢酸エチルで生成物を抽出した。更に、抽出
液の溶媒を減圧下で留去し、残金をシリカゲルカラムク
ロマトにより精製したところ、ｌ−（ブロモメチル）エ
チニルジイソプロピルカルバメート１２９ｍｇ（収＄
８６．９％）を得た。Example 1 30 mj during dry track! Put a tetra (
n-butyl) ammonium fluoride trihydrate 531
mg (Thx3), Molecu 5-C14 A 1.
0 g and then anhydrous tetrahydrofuran (THF
), and the mixture was stirred at room temperature under a nitrogen stream. Thereafter, the reaction solution was cooled to 0°C, and 194 mg (1,3-dibromo-2-propyl diisopropyl alcohol) was added (0,
562 mmol) was added thereto, and the mixture was stirred at 0°C for 2 hours. next,
The reaction solution was filtered through silica gel, and molecular sieve 4A
was removed and the product was extracted with ethyl acetate. Furthermore, the solvent of the extract was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 129 mg of l-(bromomethyl)ethynyl diisopropyl carbamate (yield: $
86.9%).
ＮＭＲ（Ｃ口α、） ６１．２６ （ｄ、
６Ｈ、Ｊ＝７．２０Ｈｚ）３、７０−４．２０ （ｂｒ
、 ２ｈ） ４．１０ （Ｓ、 ２Ｈ）４、８６
−５．０６ （ｍ、 ２ｈ）実施例２
ドライバツク中、３０ｍ１ナス型フラスコにＴＢＡＦ−
３水和物４６０ｍｇ （ＴｈＸ ５ ）及びモレキュラ
ーシーブ４ Ａ １．０ ｇを入れ、さらに無水ＴＨＦ
５ｍｌを加えた後、窒素気流下室温で攪拌した。その後
、１．３−ジブロモ−２−プロビルジイソプロビル力ル
バメー） １００ｍｇ （０，２８９７ｍモル）を加え
、５０℃で１８時間加熱攪拌した。NMR (C mouth α,) 61.26 (d,
6H, J=7.20Hz) 3, 70-4.20 (br
, 2h) 4.10 (S, 2H) 4,86
-5.06 (m, 2h) Example 2 TBAF-
Add 460 mg of trihydrate (ThX 5 ) and 1.0 g of molecular sieve 4 A, and then add anhydrous THF.
After adding 5 ml, the mixture was stirred at room temperature under a nitrogen stream. Thereafter, 100 mg (0,2897 mmol) of 1,3-dibromo-2-probildiisopropylic acid was added, and the mixture was heated and stirred at 50°C for 18 hours.
次に、反応液をシリカゲルで濾過し、モレキュラーシー
ブ４Ａを除去し、更に、濾液を水に注いだ後、酢酸エチ
ルで生成物を抽出し、水洗した。得られた酢酸エチル層
を無水硫酸ナトリウムで乾燥した後、濃縮し、残金をシ
リカゲルカラムクロマトにより精製したところ、１−（
フルオロメチル）エチニルジイソプロピル力ルバメー）
３０ｍｇ（収率５０．９％）を得た。Next, the reaction solution was filtered through silica gel to remove molecular sieve 4A, and the filtrate was poured into water, and the product was extracted with ethyl acetate and washed with water. The obtained ethyl acetate layer was dried over anhydrous sodium sulfate, concentrated, and the residue was purified by silica gel column chromatography to obtain 1-(
fluoromethyl)ethynyldiisopropyl(fluoromethyl)
30 mg (yield 50.9%) was obtained.
ＮＭＲ（ＣＤα、） ５１．２６ （ｄ、６Ｈ、Ｊ＝７
．２０Ｈｚ＞３．６０−４．１６（ｂｒ、 ２Ｂ） ４
．８６（ｄ、 ２Ｈ。NMR (CDα,) 51.26 (d, 6H, J=7
．． 20Hz>3.60-4.16(br, 2B) 4
．． 86(d, 2H.
Ｊ＝４６．８０）１ｚ）、５．０４（不溶分Ｓ、 ２）
１）実施例３
ドライバツク中、３０ｍＡ’ナス型フラスコにＴＢＡＦ
−３永和物７４１ｍｇ （Ｔｈｘ８．１ ）及びモレ
キュラーシーブ４ Ａ １．４ ｇを入れ、さらに無水
ＴＨＦ３ｍｌを加えた後、窒素気流下室温で攪拌した。J=46.80)1z), 5.04 (insoluble content S, 2)
1) Example 3 TBAF was added to a 30 mA eggplant-shaped flask during a dry pack.
741 mg (Thx8.1) of E-3 and 1.4 g of Molecular Sieve 4A were added thereto, and 3 ml of anhydrous THF was added thereto, followed by stirring at room temperature under a nitrogen stream.
その後、メタンスルホニルフルオリド１１３ｍｇ （Ｔ
ｈｘ ４ ）と１−（１，３−ジヒドロキシ−２−プロ
ピルオキシ）ナフタレン６３ｍｇ （０，２８８６ｍモ
ル）を加え、４時間加熱、還流した。Then, 113 mg of methanesulfonyl fluoride (T
hx 4 ) and 63 mg (0,2886 mmol) of 1-(1,3-dihydroxy-2-propyloxy)naphthalene were added, and the mixture was heated and refluxed for 4 hours.
次に、室温に冷却し、反応液をシリカゲルで濾過し、モ
レキュラーシーブ４Ａを除去した後、ジエチルエーテル
で生成物を抽出し、更に、溶媒を減圧下で留去し、残金
を薄層クロマトで分離精製したところ、１−（（１−（
フルオロメチル）エチニル）オキシ）すｊフタシン２８
ｍｇ （収率４８．０％）を辱た。Next, after cooling to room temperature and filtering the reaction solution through silica gel to remove molecular sieve 4A, the product was extracted with diethyl ether, the solvent was distilled off under reduced pressure, and the residue was purified by thin layer chromatography. When separated and purified, 1-((1-(
Fluoromethyl)ethynyl)oxy)futhacine 28
mg (yield 48.0%).
Ｊ＝４６．８０１ｉｚ） 、７．１０−８．０７（＋ａ
、 ７Ｈ）
実施例４
１．３−ジブロモ−２−プロパツールのテトラヒドロピ
ランエーテルにＴＨＦ中４Ａモレキュラーシーブス存在
下２．５当量のＴＢＡＦ・３水塩を作用させ５０℃で５
時間反応させた後、水処理しＰＬＣにより分離精製した
ところフルオロイソプロペニルエーテルを６９％の収率
で得た。又、原料を１，３−ジクロロ−２−プロパツー
ルのテトラヒドロビランエーテルに代えて反応を行なっ
たところ、フルオロイソプロペニルエーテルを４６％の
収率で得た。J=46.801iz), 7.10-8.07(+a
, 7H) Example 4 Tetrahydropyran ether of 1.3-dibromo-2-propatol was treated with 2.5 equivalents of TBAF trihydrate in the presence of 4A molecular sieves in THF at 50°C.
After reacting for an hour, the mixture was treated with water and separated and purified by PLC to obtain fluoroisopropenyl ether in a yield of 69%. Further, when the reaction was carried out by replacing the raw material with tetrahydrobyran ether of 1,3-dichloro-2-propanol, fluoroisopropenyl ether was obtained in a yield of 46%.
？
ＣＨ，Ｆ
ＮＭＲ（ＣＤα、） ６１．２０−１．８８ （ｍ、６
Ｈ）３、４４−４．００ （ｍ、 ２Ｈ）
４、３６−４．４８ （ｍ、ＬＨ）
４、４８−４．５６ （ｍ、 ＩＨ）
４．７２ （ｄ、２８． Ｊ＝４６．８Ｈｚ）５．１６
−５．３２（ｎ、 ＩＨ）
実施例５
原料の種類をいろいろかえて、実施例２と同様の条件で
反応を行なった。結果をまとめて表−１に示す。? CH,F NMR (CDα,) 61.20-1.88 (m, 6
H) 3,44-4.00 (m, 2H) 4,36-4.48 (m, LH) 4,48-4.56 (m, IH) 4.72 (d, 28. J=46. 8Hz) 5.16
-5.32 (n, IH) Example 5 A reaction was carried out under the same conditions as in Example 2, with various types of raw materials being changed. The results are summarized in Table-1.
各生成物の同定データを下記に示す。Identification data for each product is shown below.
Ｎα１の生成物：
Ｎ１１１１（［：［）α３）：δ１．２０（ｔ、 ３）
ＩＳＪ＝７．２０Ｈｚ）１．４２（ｄ、 ３Ｈ，Ｊ＝５
．４０Ｈｚ）３．５２（ｑ、 ２ＨＳ Ｊニア、２０
Ｈｚ）４、２４−４．４０ （ｍ、 ２ｆｌ）４．６８
（ｄ、 ２Ｈ，Ｊ＝４６．８ｔｌｚ）５．２０（ｑ、
ＩＨ，Ｊ＝５．４０１１ｚ）Ｎα２の生成物：
ＮＭＲ（ＣＤＣｊ＋） ：δ４．１６−４．３０（ｍ、
ＨＩＬ４ＪＯ−４，４０（ｍ、 １）１）、４．７７
（ｄ、 ２ＨＳＪ＝４６．８Ｈｚ＞、４．８１（３，２
旧、７．３６ （ｂｒｓ。Product of Nα1: N1111([:[)α3):δ1.20(t, 3)
ISJ=7.20Hz) 1.42(d, 3H, J=5
．． 40Hz) 3.52 (q, 2HS J near, 20
Hz) 4, 24-4.40 (m, 2fl) 4.68
(d, 2H, J=46.8tlz) 5.20(q,
IH, J = 5.4011z) Nα2 product: NMR (CDCj+): δ4.16-4.30 (m,
HIL4JO-4,40(m, 1)1), 4.77
(d, 2HSJ=46.8Hz>, 4.81(3,2
Old, 7.36 (brs.
５Ｈ）
Ｎα３の生成物：
ＮＭＲ（ＣＤαａ） ：δ１．１６（ｔ、６ＨＳＪ＝７
．２０１（ｚ）、３、３２ （ｑ、 ４Ｈ１Ｊ＝７．２
０Ｈｚ）、４．８（ｉ（ｄ、 ２Ｎ、 Ｊ＝４６．８０
Ｈｚ＞、５、０４ （ｍ、 ２Ｈ）
Ｎα４の生成物：5H) Product of Nα3: NMR (CDαa): δ1.16 (t, 6HSJ=7
．． 201(z), 3, 32 (q, 4H1J=7.2
0Hz), 4.8(i(d, 2N, J=46.80
Hz>,5,04 (m, 2H) Nα4 product:
Claims (2)
（ I ） （式中、Ｒ＿１は炭化水素基、複素環基又は▲数式、化
学式、表等があります▼で示される基（Ｒ＿２及びＲ＿
３はアルキル基を示す）であり、Ｘは、ハロゲン又はア
ルキルスルホニルオキシ基を示す。） で表わされるイソプロピルエーテル又はエステル誘導体
に第４級アンモニウムフルオリドを作用させて、ＨＸ（
Ｘは上記と同じ意味を有する。）を脱離させることを特
徴とする一般式（II）：▲数式、化学式、表等がありま
す▼・・・・・・・・・（II） （式中、Ｒ＿１とＸは上記と同じ意味を有する。）で表
わされるイソプロペニルエーテル又はエステル誘導体の
製造方法。(1) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
(I) (In the formula, R_1 is a hydrocarbon group, a heterocyclic group, or a group represented by ▲ has a numerical formula, chemical formula, table, etc.) (R_2 and R_
3 represents an alkyl group), and X represents a halogen or an alkylsulfonyloxy group. ) is reacted with quaternary ammonium fluoride to the isopropyl ether or ester derivative represented by HX(
X has the same meaning as above. ) General formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・(II) A method for producing an isopropenyl ether or ester derivative represented by
（ I ） （式中、Ｒ＿１は炭化水素基、複素環基又は▲数式、化
学式、表等があります▼で示される基（Ｒ＿２及びＲ＿
３はアルキル基を示す。）であり、Ｘはハロゲン又はア
ルキルスルホニルオキシ基を示す。） で表わされるイソプロピルエーテル又はエステル誘導体
に第４級アンモニウムフルオリドを作用させて、ＨＸ（
Ｘは上記と同じ意味を有する）を脱離させた後フッ素化
することを特徴とする一般式（III）： ▲数式、化学式、表等があります▼・・・・・・・・・
（II） （式中、Ｒ＿１は上記と同じ意味を有する。）で表わさ
れるイソプロペニルエーテル又はエステル誘導体の製造
方法。(2) General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
(I) (In the formula, R_1 is a hydrocarbon group, a heterocyclic group, or a group represented by ▲ has a numerical formula, chemical formula, table, etc.) (R_2 and R_
3 represents an alkyl group. ), and X represents a halogen or an alkylsulfonyloxy group. ) is reacted with quaternary ammonium fluoride to the isopropyl ether or ester derivative represented by HX(
General formula (III) characterized by elimination of X (X has the same meaning as above) followed by fluorination: ▲There are numerical formulas, chemical formulas, tables, etc.▼・・・・・・・・・
(II) A method for producing an isopropenyl ether or ester derivative represented by (wherein R_1 has the same meaning as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5006886A JPS62207235A (en) | 1986-03-07 | 1986-03-07 | Production of isopropenyl ether or ester derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5006886A JPS62207235A (en) | 1986-03-07 | 1986-03-07 | Production of isopropenyl ether or ester derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62207235A true JPS62207235A (en) | 1987-09-11 |
Family
ID=12848677
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5006886A Pending JPS62207235A (en) | 1986-03-07 | 1986-03-07 | Production of isopropenyl ether or ester derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62207235A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011173830A (en) * | 2010-02-24 | 2011-09-08 | Nippon Zeon Co Ltd | Method for producing alkyne, and method for purifying 2-butyne |
| JP2013510149A (en) * | 2009-11-03 | 2013-03-21 | ダウ グローバル テクノロジーズ エルエルシー | Vinyl ether compounds and methods for their production and use |
-
1986
- 1986-03-07 JP JP5006886A patent/JPS62207235A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013510149A (en) * | 2009-11-03 | 2013-03-21 | ダウ グローバル テクノロジーズ エルエルシー | Vinyl ether compounds and methods for their production and use |
| JP2011173830A (en) * | 2010-02-24 | 2011-09-08 | Nippon Zeon Co Ltd | Method for producing alkyne, and method for purifying 2-butyne |
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