JPS62198639A - Production of alpha-arylcarbonyl derivative - Google Patents
Production of alpha-arylcarbonyl derivativeInfo
- Publication number
- JPS62198639A JPS62198639A JP61040833A JP4083386A JPS62198639A JP S62198639 A JPS62198639 A JP S62198639A JP 61040833 A JP61040833 A JP 61040833A JP 4083386 A JP4083386 A JP 4083386A JP S62198639 A JPS62198639 A JP S62198639A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- mmol
- lower alkyl
- arylcarbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- -1 methylenedioxy Chemical group 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 8
- 150000001502 aryl halides Chemical class 0.000 abstract description 6
- 150000002941 palladium compounds Chemical class 0.000 abstract description 6
- 229910000073 phosphorus hydride Inorganic materials 0.000 abstract description 6
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 abstract description 5
- 150000002466 imines Chemical class 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 239000002778 food additive Substances 0.000 abstract description 4
- 235000013373 food additive Nutrition 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract description 2
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 abstract description 2
- 239000007859 condensation product Substances 0.000 abstract 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000002304 perfume Substances 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000009835 boiling Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
- 239000003205 fragrance Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical group 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 229940100595 phenylacetaldehyde Drugs 0.000 description 2
- DRLVMOAWNVOSPE-UHFFFAOYSA-N 2-phenylcyclohexan-1-one Chemical compound O=C1CCCCC1C1=CC=CC=C1 DRLVMOAWNVOSPE-UHFFFAOYSA-N 0.000 description 1
- BHRKSAPSDAMHIB-UHFFFAOYSA-N 4-phenyl-1,3-dioxan-5-one Chemical compound O=C1COCOC1C1=CC=CC=C1 BHRKSAPSDAMHIB-UHFFFAOYSA-N 0.000 description 1
- FBOYMIDCHINJKC-UHFFFAOYSA-N 5-bromo-1,3-benzodioxole Chemical compound BrC1=CC=C2OCOC2=C1 FBOYMIDCHINJKC-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 1
- XQJHRCVXRAJIDY-UHFFFAOYSA-N aminophosphine Chemical group PN XQJHRCVXRAJIDY-UHFFFAOYSA-N 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001499 aryl bromides Chemical class 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
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical group C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- QCCDLTOVEPVEJK-UHFFFAOYSA-N phenylacetone Chemical compound CC(=O)CC1=CC=CC=C1 QCCDLTOVEPVEJK-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011269 tar Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、医薬品、食品添加物、香料等の合成中間体と
して有用な次の一般式（１）
（式中、Ｒ１及びＲ２は水素原子、低級アルキル基又は
低級アルコキシ基を示すか、または両者が一緒になって
メチレンジオキシ基を示す。ＦｔＸ及びＲ４は水素原子
又は低級アルキル基を示すか、または両者が一緒になっ
て５〜７員のシクロアルキル環を形成する）
で表わされるａ−アリールカルボニル誘導体を製造する
方法に関する。Detailed Description of the Invention [Industrial Application Field] The present invention relates to the following general formula (1), which is useful as a synthetic intermediate for pharmaceuticals, food additives, fragrances, etc. (wherein R1 and R2 are hydrogen atoms) , represents a lower alkyl group or a lower alkoxy group, or both together represent a methylenedioxy group.FtX and R4 represent a hydrogen atom or a lower alkyl group, or both together represent a 5-7 It relates to a method for producing an a-arylcarbonyl derivative represented by:
従来、アリール化合物をアセトニル化してα−アリール
カルボニル誘導体を製造する方法としては、次の方法が
知られている。Conventionally, the following method is known as a method for producing an α-arylcarbonyl derivative by acetonylating an aryl compound.
〔ザ・ジャーナル・オブ・オーガニック・ケミス ト
リ イ （Ｊ、 Ｏｒｇ、 Ｃｈｅｍ、 ）
、 ４９ 、 １６０３（収率７３％）
〔ジャーナル・オブ・ザ・アメリカン・ケミカルーンサ
イエテイ（Ｊ、 Ａｍ、 Ｃｈｅｔｎ、 Ｓｏｃ、 ）
、９６、ｐｈゆ人 （収率７８％）
〔ケεストリイ・レターズ（Ｃｈｅｍ、 Ｌｅｔｔ、
）、１９８２、９３９〕
（収率７９チ）
〔テトラヘドロン拳しターズ（Ｔｅｔｒａｈｅｄｒｏｎ
Ｌｅｔｔ、）、２１．２３２５（１９８０））〔ケミス
トリイ・レターズ（Ｃｈｅｍ、 Ｌｅｔｔ、 ）、１９
７６．１２３９）
〔発明が解決しようとする問題点〕
しかしながら、上記の従来法は収率が低いか、あるいは
収率を上げようとすると、有機Ｎ１化合物、有機Ｓｎ化
合物、有機Ｌ１化合物、有機Ｓｔ化合物等の特殊で高価
な原料を使用しなければならないという欠点が１、従来
アリール化合物のアセトニル化反応によるアリールカル
ボニル誘導体の製造法は困難であるとされていた。[The Journal of Organic Chemist]
Lii (J, Org, Chem, )
, 49, 1603 (yield 73%) [Journal of the American Chemical Society (J, Am, Chetn, Soc, )
, 96, phyuto (yield 78%) [Chem, Lett,
), 1982, 939] (Yield: 79 cm) [Tetrahedron Fisted Tars
Lett, ), 21.2325 (1980) [Chemistry Letters (Chem, Lett, ), 19
76.1239) [Problems to be solved by the invention] However, the above conventional method has a low yield, or when trying to increase the yield, organic N1 compound, organic Sn compound, organic L1 compound, organic St The method of producing aryl carbonyl derivatives by acetonylation reaction of aryl compounds has been considered difficult in the past, as it has the disadvantage of requiring the use of special and expensive raw materials such as compounds.
従って、本発明の目的は、安価な原料を使用して、簡便
な操作で収率よくアリールカルボニル誘導体を製造する
方法を提供せんとするものである。Therefore, an object of the present invention is to provide a method for producing arylcarbonyl derivatives in good yields using inexpensive raw materials and simple operations.
斯かる実状において、本発明者らは鋭意研究を行った結
果、原料としてアリールハライドとイミン化合物を用い
、パラジウム化合物、第３級ホスフィン及び塩基の存在
下に反応させれば、容易にアリール化合物のアセトニル
化が達成されることを見出し、本発明を完成した。Under such circumstances, the present inventors conducted intensive research and found that aryl compounds can be easily formed by using aryl halides and imine compounds as raw materials and reacting them in the presence of a palladium compound, tertiary phosphine, and a base. They discovered that acetonylation can be achieved and completed the present invention.
本発明方法は次の反応式によって示される。The method of the present invention is shown by the following reaction formula.
（ＩＶ）
Ｃ式中、Ｘはハロゲン原子、島は低級アルキル基又はシ
クロへ午シル基を示す。Ｒ１＋ ａｍ ｌ Ｒ１及び電
は前記と同じものを示す）
すなわち、本発明は、アリールハライド（Ｉｔ）とイミ
ン化合物（ＩＩＩ）とを、パラジウム化合物、第３級ホ
スフィン及び塩基の存在下に縮合せしめ、次いでその成
績体を加水分解してα−アリールカルボニル誘導体（１
）を製造する方法である。(IV) In the formula C, X represents a halogen atom, and the island represents a lower alkyl group or a cyclosyl group. R1+ am l R1 and electron are the same as above) That is, the present invention condenses an aryl halide (It) and an imine compound (III) in the presence of a palladium compound, a tertiary phosphine and a base, Next, the resulting product was hydrolyzed to obtain an α-arylcarbonyl derivative (1
).
以下、本発明を更に詳細に説明する。The present invention will be explained in more detail below.
本発明の原料であるアリールハライド（ＩＩ）としては
アリールブロマイドが最も好適に用いられ、もう一つの
原料であるイミン化合物（Ｉｔ）は相当するアルデヒド
またはケトンと第１級アミンとの反応により容易に得ら
れるものである。Aryl bromide is most preferably used as the aryl halide (II), which is the raw material of the present invention, and the imine compound (It), which is another raw material, can be easily prepared by reacting the corresponding aldehyde or ketone with a primary amine. That's what you get.
本発明に用いられるパラジウム化合物は、パラジウムに
塩素が結合したもの、カルボニル化合物が結合したもの
、ジエン化合物が結合したもの等が用いられるが、その
中でもカルボニル化合物が結合したもの、例えばＰｄ
（ＯＣＣＨｓ ）！、Ｐｄ（ａｃａｃ）２［ａｃａｃは
アセチルアセトネートを示す］、Ｐｄ（ｄｂａ）［ｄｂ
ａはジベンザルアセトンを示す〕等が好適に用いられる
。The palladium compounds used in the present invention include those in which chlorine is bound to palladium, those in which a carbonyl compound is bound to palladium, and those in which a diene compound is bound to palladium. Among these, those in which a carbonyl compound is bound to palladium, such as Pd
(OCCHs)! , Pd(acac)2 [acac represents acetylacetonate], Pd(dba)[db
a represents dibenzalacetone], etc. are preferably used.
第３級ホスフィンとしては、アミノホスフィンが好適で
あり、例えば、（ＥｔｔＮ＋ｉ−Ｐ 、 （１−Ｐｒｚ
Ｎ＋ｒＰ。As the tertiary phosphine, aminophosphine is suitable; for example, (EttN+i-P, (1-Prz
N+rP.
られる。It will be done.
また塩基としては、アルコール類のＮａまたはに塩、そ
の中でもラジウムｔ−ブチラード（１−ＢｕＯＮａ ）
、メジウムｔ−アミラード（ｔ −Ａｒｎ０Ｎａ ）
が好適に用いられる。In addition, as a base, salts of Na or alcohols, especially radium t-butyralate (1-BuONa)
, medium t-amylard (t-Arn0Na)
is preferably used.
本発明によりα−アリールカルボニル誘導体を製造する
には通常次のようにして行われる。すなわち、Ｎ２置換
した耐圧反応管にアリールハライド１００ミリモルに対
し、イミン化合物１５０〜４００ミリモル、パラジウム
化合物０．０５〜０．２ミリモル、第３級ホスフィン０
．２〜１．０ミリモル、塩基１０５〜１２０ミリモル、
溶媒（テトラヒドロフランまたはトルエンが好ましい）
５０〜１００ｍ１を加え、加熱攪拌する。反応温度は６
０〜１４０℃、好ましくは８０〜１１０℃が適当であり
、反応時間は原料によって異るが、通常１時間〜１５時
間を要する。The production of α-arylcarbonyl derivatives according to the present invention is generally carried out as follows. That is, in a pressure-resistant reaction tube substituted with N2, for 100 mmol of aryl halide, 150 to 400 mmol of an imine compound, 0.05 to 0.2 mmol of a palladium compound, and 0 mmol of tertiary phosphine were added.
．． 2-1.0 mmol, base 105-120 mmol,
Solvent (preferably tetrahydrofuran or toluene)
Add 50 to 100 ml and heat and stir. The reaction temperature is 6
A suitable temperature is 0 to 140°C, preferably 80 to 110°C, and the reaction time varies depending on the raw materials, but usually takes 1 to 15 hours.
斯くすると、上記一般式（ＩＶ）で表わされる化合物と
推定される成績体が得られるが、これは単離することな
く、次の加水分解に付すことができる。In this way, a product presumed to be the compound represented by the above general formula (IV) is obtained, but this can be subjected to the next hydrolysis without isolation.
加水分解は、上記反応液に塩酸、酢酸、シュウ酸、クエ
ン酸等の酸の水溶液を加えて微酸性（ｐＨ５〜６）とし
、数時間攪拌することによって行われる。次いで、この
反応液から有機層を分取し、乾燥後、濃縮、蒸留を行え
ば目的物（１）が得られる。Hydrolysis is carried out by adding an aqueous solution of an acid such as hydrochloric acid, acetic acid, oxalic acid, or citric acid to the reaction solution to make it slightly acidic (pH 5 to 6), and stirring for several hours. Next, the organic layer is separated from this reaction solution, dried, concentrated, and distilled to obtain the desired product (1).
このようにして本発明で得られるα−アリールカルボニ
ル誘導体は、医薬品、食品添加物、香料等の合成中間体
として有用であり、例えばフェニルアセトアルデヒドは
香料としてまたフェニルアラニンの合成中間体として用
いられ、３．４−ジメトキシフェニルアセトンは血圧降
下剤として重要なａ−メチルドーパの合成中間体として
用いられる。The α-arylcarbonyl derivatives thus obtained in the present invention are useful as synthetic intermediates for pharmaceuticals, food additives, fragrances, etc. For example, phenylacetaldehyde is used as a fragrance and as a synthetic intermediate for phenylalanine. 4-dimethoxyphenylacetone is used as an intermediate in the synthesis of a-methyldopa, which is important as an antihypertensive agent.
以下に実施例をあげて本発明をさらに詳しく説明する。 The present invention will be explained in more detail with reference to Examples below.
実施例１
フェニルアセトンの合成：
１’ｈｉｌ換した耐圧反応管にブロムベンゼン１５．７
Ｆ（１００ミリモル）、２−プロピリデンシクロヘキシ
ルイミン４１．７Ｆ（３００ミリモル）、１ ４ ７
”７ １ ０． ４ ミ リ モ ル） 、
ｔ−ＢｕＯＮａ １０．５ ｔ（１１０ミリモル
）、テトラヒドロフラン８０ゴを加え、９０℃で８時間
反応させた。反応終了後、トルエン２００ｍ、水２００
屑ｌを加え、氷水冷却下に２Ｎ−シュウ酸水溶液を滴下
してｐＨ５，５に調整し、２時間攪拌を続けて加水分解
を完了させた。Example 1 Synthesis of phenylacetone: 15.7 ml of bromobenzene was added to a 1'hil-converted pressure-resistant reaction tube.
F (100 mmol), 2-propylidenecyclohexylimine 41.7F (300 mmol), 1 4 7
”7 1 0.4 mmol),
10.5 t (110 mmol) of t-BuONa and 80 g of tetrahydrofuran were added, and the mixture was reacted at 90°C for 8 hours. After the reaction is complete, add 200 m of toluene and 200 m of water.
One scrap was added, and while cooling with ice water, a 2N aqueous oxalic acid solution was added dropwise to adjust the pH to 5.5, and stirring was continued for 2 hours to complete hydrolysis.
有機層を分液し、乾燥、濃縮後、蒸留を行って本化合物
９．１Ｆ（収率６７．９係）を沸点８６〜８７℃／ ６
ｍ Ｈｙの留分として得た。The organic layer was separated, dried, concentrated, and then distilled to obtain the present compound 9.1F (yield 67.9%) with a boiling point of 86-87℃/6
Obtained as a fraction of mHy.
本化合物のＭＳ、ＮＭａは次の通りであった。The MS and NMa of this compound were as follows.
Ｍｓ（ｍ／ｅ）： １３４（Ｍ”）、９１．４３３．６
０（２Ｈ，ｓ、−ＣＨｚ−）
７．０９（５Ｈ，ブロードＳ、ベンゼン項のＣ猛）
実施例２
フェニルアセトアルデヒドの合成：
Ｎ！置換した耐圧反応管にヨウ化ベンゼン２０，４ｒ（
１００ミリ七ル）、エチリデンシクロへキシルイミン３
７．２ｆ（３００ミリモル） 、ｐｄ（ａｃａｃ）２ｖ
ｑ（０，４ミ リ モル ） 、 ｔ−ＢｕＯＮａ
１ ０． ５ ｆ （１１０ミリモル）、テト
ラヒドロフラン８ｏ−を加え１９０℃で８時間反応させ
た。以後の操作は実施例１と同様に行い、本化合物６．
２ｆ（収率ｓｘ、７％）を沸点７７〜７８℃／ １０
ｍＨｙの留分として得た。Ms (m/e): 134 (M”), 91.433.6
0 (2H, s, -CHz-) 7.09 (5H, broad S, C of benzene term) Example 2 Synthesis of phenylacetaldehyde: N! Add benzene iodide 20.4r (
100 ml), ethylidenecyclohexylimine 3
7.2f (300 mmol), pd(acac)2v
q (0.4 mmol), t-BuONa
1 0. 5 f (110 mmol) and 8 o of tetrahydrofuran were added, and the mixture was reacted at 190°C for 8 hours. The subsequent operations were performed in the same manner as in Example 1, and the present compound 6.
2f (yield sx, 7%) with boiling point 77-78℃/10
Obtained as a mHy fraction.
本化合物のＮＭＲは次の通シであった。The NMR of this compound was as follows.
ＮＮ Ｒ（ＣＪ）Ｃ２３＋ ｐｐｍ） ： ２．６７
（２Ｈ、ｄ 、 −ＣＨｒＣＨＯ）７．００−７．７０
（５Ｈ，ｍ、ベンゼン環のＣＨ）９．７１ （ＩＨ、ｔ
、−ＣＨｚ・Ｃ猛０）実施例３
２−フェニルシクロヘキサノンの合成二Ｎ！置換した耐
圧反応管にブロムベンゼン１５．７ｆ（１００ミリモル
）、シクロヘキシリデンシクロへキシルイミン２７．１
？ （１５０ミリモル）、Ｐｄ（ａｃａｃ）ｚ ３
０．５ Ｗ （０，１ミリモル）、（１−ＰｒｔＮ＋ｒ
Ｐ １３２ ’Ｆ （０，４ミリモル）、を−ｈｒｎ
ＯＮａ １２．１ ？ （１１０ミリモル）、テトラヒ
ドロ７ラン８０ｍ１を加え、９０℃で８時間反応させた
。以後の操作は実施例１と同様に行い、本化合物８．２
Ｆ（収率４７．１％）を沸点９３〜９５℃１０、１ ｍ
ｘＨｙの留分として得た。NN R(CJ)C23+ ppm): 2.67
(2H, d, -CHrCHO)7.00-7.70
(5H, m, CH of benzene ring)9.71 (IH, t
, -CHz・C 0) Example 3 Synthesis of 2-phenylcyclohexanone 2N! In the replaced pressure-resistant reaction tube, 15.7 f (100 mmol) of bromobenzene and 27.1 g of cyclohexylidenecyclohexylimine were added.
? (150 mmol), Pd(acac)z 3
0.5 W (0.1 mmol), (1-PrtN+r
P 132 'F (0,4 mmol), -hrn
ONa 12.1? (110 mmol) and 80 ml of tetrahydro7ran were added and reacted at 90°C for 8 hours. The subsequent operations were performed in the same manner as in Example 1, and the present compound 8.2
F (yield 47.1%) at boiling point 93-95℃ 10, 1 m
Obtained as a fraction of xHy.
本化合物のＭＳは次の通りであった。The MS of this compound was as follows.
ＭＳ（ｍ／ｅ）： １８４（Ｍ”）、１０７．７７実
施例４
３．４−ジメトキシフェニルアセ・トンの合成二Ｎ２置
換した耐圧反応管に３，４−ジメトキシフェニルアセミ
）’ ２１．７ Ｆ （１００ミリモル）、２−プロピ
リデンシクロヘキシルイミン４１．７ｆ（３００ミリモ
ル）、Ｐｄ （ＯＣＣＨｓ ）＊ ２２．５ ”９
（０，１１！
ｔ−ＢｕＯＮａ １０．５ ｆ （１１０ミリモル）、
テトラヒドロフラン８０．ｄを加え、１００℃で１０時
間反応させた。以後の操作は実施例１と同様に行い本化
合物１３．５Ｆ（収率６９．６チ）を沸点１４６〜１４
７℃／ ６ ｗＨｙの留分として得た。MS (m/e): 184 (M"), 107.77 Example 4 Synthesis of 3.4-dimethoxyphenylacetone 3,4-dimethoxyphenylacemite)' in a pressure-resistant reaction tube with diN2 substitution.'21. 7F (100 mmol), 2-propylidenecyclohexylimine 41.7f (300 mmol), Pd (OCCHs) * 22.5 ”9
(0,11! t-BuONa 10.5 f (110 mmol),
Tetrahydrofuran80. d was added and reacted at 100°C for 10 hours. The subsequent operations were carried out in the same manner as in Example 1, and the present compound 13.5F (yield: 69.6%) was obtained with a boiling point of 146-14%.
Obtained as a fraction at 7°C/6 wHy.
本化合物のＮＭＲは次の通りであった。NMR of this compound was as follows.
３．６２（２Ｈ，ｓ、−Ｃ少−）
３．８９（６Ｈ，ｓ、Ｃ猛３Ｏ−）
６．６８＝６：９０（３Ｈ，ｍ、ベンゼン環のＣＨ）実
施例５
３．４−メチレンジオキシフェニルアセトンの合成二Ｎ
２置換した耐圧反応管に３，４−メチレンジオキシフェ
ニルプロミド２０．１ ？ （１００ミリモル）、２−
プロピリデンシクロヘキシルイミン４１．７Ｆ（３００
ミ リ モル ） 、 Ｐｄ（ａｃａｃ）ｇ ３
０． ５ ｗｑ （０，１ル）、ｔ−Ａ＋ｎ０Ｎａ １
２．１ ？ （１１０ミリモル）、テトラヒドロフラン
８０ｍ１を加え、１００℃で１０時間反応させた。以後
の操作は実施例１と同様に行い、本化合物１２．６Ｆ（
収率７０．８％）を沸点１０１〜１０４℃１０．１龍Ｈ
２の留分として得た。3.62 (2H, s, -C low-) 3.89 (6H, s, C 3O-) 6.68 = 6:90 (3H, m, CH of benzene ring) Example 5 3.4- Synthesis of methylenedioxyphenylacetone 2N
3,4-methylenedioxyphenyl bromide 20.1 ? (100 mmol), 2-
Propylidenecyclohexylimine 41.7F (300
mmol), Pd(acac)g3
0. 5 wq (0,1 l), t-A+n0Na 1
2.1? (110 mmol) and 80 ml of tetrahydrofuran were added, and the mixture was reacted at 100° C. for 10 hours. The subsequent operations were performed in the same manner as in Example 1, and the present compound 12.6F (
Yield: 70.8%) Boiling point: 101-104℃ 10.1 Dragon H
Obtained as fraction 2.
本化合物のＮＭＲは次の通シであった。The NMR of this compound was as follows.
ＮＭＲ（ＣＤＣｌ２９ｐｐｍ）： ２．１５（３Ｈ，ｓ
、ＣＨｓＣ−）３．８０（２Ｈ，ｓ、−Ｃ少−）
５．９６（２Ｈ，ｓ、−ＱＣＣＯ２）
６．６０〜６．８４ （３Ｈ、＋ｎ 、ベンゼ＄ ＣＨ
）〔発明の効果〕
本発明によれば、安価な原料によシ、簡便にかつ収率よ
くアリール化合物のアセトニル化を行うことができ、医
薬品、食品添加物、香料等の合成中間体として有用なα
−アリールカルボニル紡導体を経済的に得ることができ
る
以上NMR (CDCl29ppm): 2.15 (3H,s
, CHsC-) 3.80 (2H, s, -C low-) 5.96 (2H, s, -QCCO2) 6.60-6.84 (3H, +n, benzene $ CH
) [Effects of the Invention] According to the present invention, aryl compounds can be acetonylated easily and with high yield using inexpensive raw materials, and are useful as synthetic intermediates for pharmaceuticals, food additives, fragrances, etc. α
- As long as aryl carbonyl spinners can be obtained economically
Claims (1)
又は低級アルコキシ基を示すか、または両者が一緒にな
ってメチレンジオキシ基を形成する。 Ｘはハロゲン原子を示す） で表わされるアリールハライドと、一般式（III）▲数
式、化学式、表等があります▼（III） （式中、Ｒ＿３及びＲ＿４は水素原子又は低級アルキル
基を示すか、または両者が一緒になって５〜７員のシク
ロアルキル環を形成する。Ｒ＿５は低級アルキル基又は
シクロヘキシル基を示す） で表わされるイミン化合物とを、パラジウム化合物、第
３級ホスフィン及び塩基の存在下に縮合せしめ、次いで
その成績体を加水分解することを特徴とする一般式（
I ） ▲数式、化学式、表等があります▼（ I ） （式中、Ｒ＿１、Ｒ＿２、Ｒ＿３及びＲ＿４は前記と同
じものを示す） で表わされるα−アリールカルボニル誘導体の製造法。[Claims] 1. General formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, R_1 and R_2 represent a hydrogen atom, a lower alkyl group, a lower alkoxy group, or both together form a methylenedioxy group. and R_4 represent a hydrogen atom or a lower alkyl group, or both together form a 5- to 7-membered cycloalkyl ring. R_5 represents a lower alkyl group or a cyclohexyl group. , the general formula (
I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) A method for producing an α-arylcarbonyl derivative represented by (in the formula, R_1, R_2, R_3 and R_4 are the same as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61040833A JPS62198639A (en) | 1986-02-26 | 1986-02-26 | Production of alpha-arylcarbonyl derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61040833A JPS62198639A (en) | 1986-02-26 | 1986-02-26 | Production of alpha-arylcarbonyl derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62198639A true JPS62198639A (en) | 1987-09-02 |
| JPH0457659B2 JPH0457659B2 (en) | 1992-09-14 |
Family
ID=12591637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61040833A Granted JPS62198639A (en) | 1986-02-26 | 1986-02-26 | Production of alpha-arylcarbonyl derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62198639A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997015549A1 (en) * | 1995-10-26 | 1997-05-01 | Tokyo Tanabe Company Limited | PHENYLETHANOLAMINE COMPOUNDS USEFUL AS β3 AGONIST, PROCESS FOR PRODUCING THE SAME, AND INTERMEDIATES IN THE PRODUCTION OF THE SAME |
-
1986
- 1986-02-26 JP JP61040833A patent/JPS62198639A/en active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997015549A1 (en) * | 1995-10-26 | 1997-05-01 | Tokyo Tanabe Company Limited | PHENYLETHANOLAMINE COMPOUNDS USEFUL AS β3 AGONIST, PROCESS FOR PRODUCING THE SAME, AND INTERMEDIATES IN THE PRODUCTION OF THE SAME |
| US6069176A (en) * | 1995-10-26 | 2000-05-30 | Mitsubishi-Tokyo Pharmaceuticals, Inc. | Phenylethanolamine compounds useful as β 3 agonists, process for producing the same, and intermediates in the production of the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0457659B2 (en) | 1992-09-14 |
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