JP2017149687A - O-benzenesulfonyl-acetohydroxamic acid ester derivative and manufacturing method of nitryl compound - Google Patents
O-benzenesulfonyl-acetohydroxamic acid ester derivative and manufacturing method of nitryl compound Download PDFInfo
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- -1 O-benzenesulfonyl-acetohydroxamic acid ester Chemical class 0.000 title claims abstract description 61
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- 239000003377 acid catalyst Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 8
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 238000003786 synthesis reaction Methods 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical group OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 10
- ZXMGHDIOOHOAAE-UHFFFAOYSA-N 1,1,1-trifluoro-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)F ZXMGHDIOOHOAAE-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 5
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 5
- 150000002443 hydroxylamines Chemical class 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 150000002923 oximes Chemical class 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract 2
- 238000006243 chemical reaction Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000002825 nitriles Chemical class 0.000 description 9
- 150000001299 aldehydes Chemical group 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- AZKDTTQQTKDXLH-UHFFFAOYSA-N naphthalene-2-carbonitrile Chemical compound C1=CC=CC2=CC(C#N)=CC=C21 AZKDTTQQTKDXLH-UHFFFAOYSA-N 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920000742 Cotton Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 3
- 239000003905 agrochemical Substances 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical class C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 2
- AYTCGEDNSBGRFI-UHFFFAOYSA-N (butanoylamino) benzenesulfonate Chemical compound CCCC(=O)NOS(=O)(=O)C1=CC=CC=C1 AYTCGEDNSBGRFI-UHFFFAOYSA-N 0.000 description 2
- PJKVFARRVXDXAD-UHFFFAOYSA-N 2-naphthaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CC=C21 PJKVFARRVXDXAD-UHFFFAOYSA-N 0.000 description 2
- 0 CC(*)=NOS(c1ccc(*)cc1)(=O)=O Chemical compound CC(*)=NOS(c1ccc(*)cc1)(=O)=O 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229960001171 acetohydroxamic acid Drugs 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- MFSUKOCGNJOMDD-UHFFFAOYSA-N n-ethoxyacetamide Chemical compound CCONC(C)=O MFSUKOCGNJOMDD-UHFFFAOYSA-N 0.000 description 2
- CCBCHURBDSNSTJ-UHFFFAOYSA-N n-hydroxybutanamide Chemical compound CCCC(=O)NO CCBCHURBDSNSTJ-UHFFFAOYSA-N 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- LCRCBXLHWTVPEQ-UHFFFAOYSA-N 2-phenylbenzaldehyde Chemical compound O=CC1=CC=CC=C1C1=CC=CC=C1 LCRCBXLHWTVPEQ-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 1
- 239000007848 Bronsted acid Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 238000005609 Rosenmund-von Braun cyanation reaction Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052760 oxygen Chemical group 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
Description
本発明は、Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体、ニトリル合成試薬およびニトリル化合物の製造方法に関する。 The present invention relates to an O-benzenesulfonyl-acetohydroxamic acid ester derivative, a nitrile synthesis reagent, and a method for producing a nitrile compound.
一般的な芳香族ニトリル化合物の合成方法としては、ザントマイヤー反応やローゼンムント・フォンブラウン反応が利用され、また、脂肪族ニトリル化合物の合成には、シアニド−ハロゲン交換反応が利用されているが、毒性が高いシアン化銅（Ｉ）などの金属シアニドを用いる必要がある。また、アミドやアルドキシムの脱水反応からもニトリルが合成できることが知られているが、重金属や激しい反応条件が求められている。 As a general method for synthesizing an aromatic nitrile compound, the Zantmeier reaction or Rosenmund von Braun reaction is used, and for the synthesis of an aliphatic nitrile compound, a cyanide-halogen exchange reaction is used. It is necessary to use a metal cyanide such as copper (I) cyanide having high toxicity. It is also known that nitriles can be synthesized from dehydration reaction of amides and aldoximes, but heavy metals and harsh reaction conditions are required.
一方、アルデヒドと酸素置換されたヒドロキシルアミンを用いた方法は、無触媒や温和な条件でニトリルを合成することができる（例えば、非特許文献１および２）。しかしながら、反応剤として用いる酸素置換されたヒドロキシルアミンは熱にも弱く、分解・爆発性を有する危険な試薬のため、非常に扱いにくい。そこで、より安全で温和な条件でニトリル誘導体の製造方法の開発が求められていた。 On the other hand, the method using hydroxylamine substituted with aldehyde and oxygen can synthesize nitrile under non-catalytic or mild conditions (for example, Non-Patent Documents 1 and 2). However, the oxygen-substituted hydroxylamine used as a reactant is also difficult to handle because it is also vulnerable to heat and is a dangerous reagent with decomposition and explosive properties. Therefore, development of a method for producing a nitrile derivative under safer and milder conditions has been demanded.
本発明は、保存性や取扱性に問題があるヒドロキシルアミン誘導体を使用しないニトリル化合物を製造するための新規な合成試薬を提供することを目的とする。 An object of this invention is to provide the novel synthetic reagent for manufacturing the nitrile compound which does not use the hydroxylamine derivative which has a problem in storage stability or handleability.
本発明者らは、新規なニトリル合成試薬について種々検討したところ、酸素置換された安定なオキシム化合物を酸素置換されたヒドロキシルアミン等価体とみなし、簡便でかつ温和な条件のもとアルデヒドからニトリルへの変換を可能になることを見出した。また、ブレンステッド酸触媒と触媒量の水によって、新規ニトリル合成試薬である酸素置換されたアセトヒドロキサム酸エチルからアルデヒドへのトランスオキシム化反応が進行し、酸素置換されたアルドキシムが合成され、さらに合成されたアルドキシム中間体が酸触媒によってニトリルへと変換できることも見出し、本発明を完成した。 The present inventors have made various studies on a novel nitrile synthesis reagent. As a result, the stable oxygen-substituted oxime compound is regarded as an oxygen-substituted hydroxylamine equivalent, and the aldehyde is converted into a nitrile under simple and mild conditions. It was found that conversion is possible. In addition, a transoximation reaction from oxygen-substituted ethyl acetohydroxamic acid, which is a new nitrile synthesis reagent, to aldehyde proceeds with a Bronsted acid catalyst and a catalytic amount of water, and oxygen-substituted aldoxime is synthesized and further synthesized. It was also found that the aldoxime intermediate produced can be converted to nitrile by an acid catalyst, and the present invention has been completed.
すなわち、本発明は、下記化学式
で表されるＯ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体に関する。
That is, the present invention has the following chemical formula:
The present invention relates to an O-benzenesulfonyl-acetohydroxamic acid ester derivative represented by:
また、前記Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体を含む、アルデヒド化合物からニトリル化合物を合成するためのニトリル化合物合成試薬に関する。 In addition, the present invention relates to a nitrile compound synthesis reagent for synthesizing a nitrile compound from an aldehyde compound, including the O-benzenesulfonyl-acetohydroxamic acid ester derivative.
さらに、前記合成試薬、有機溶媒、酸触媒の存在下で、アルデヒド化合物をトランスオキシム化させる工程を含むニトリル化合物の製造方法に関する。 Furthermore, it is related with the manufacturing method of a nitrile compound including the process of transoximing an aldehyde compound in presence of the said synthetic reagent, an organic solvent, and an acid catalyst.
酸触媒が、過塩素酸、トリフルオロメタンスルホン酸、ビストリフルオロメタンスルホンイミド、パラクロロベンゼンスルホン酸、または、ベンゼンスルホン酸であることが好ましい。 The acid catalyst is preferably perchloric acid, trifluoromethanesulfonic acid, bistrifluoromethanesulfonimide, parachlorobenzenesulfonic acid, or benzenesulfonic acid.
有機溶媒が、塩化メチレン、クロロホルム、ヘキサン、または、トルエンであることが好ましい。 The organic solvent is preferably methylene chloride, chloroform, hexane, or toluene.
本発明によれば、ヒドロキシルアミン等価体としてオキシム化合物を扱うことができるため、温和な反応条件で、高収率でアルデヒドからニトリル化合物を得ることができる。また、得られたニトリル化合物は、医薬品、農薬、化粧品、香料及びそれらの原材料として有用である。 According to the present invention, since an oxime compound can be handled as a hydroxylamine equivalent, a nitrile compound can be obtained from an aldehyde in a high yield under mild reaction conditions. Moreover, the obtained nitrile compound is useful as a pharmaceutical, an agricultural chemical, cosmetics, a fragrance | flavor, and those raw materials.
本発明のＯ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体は、下記化学式
で表されることを特徴とする。Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体は、たとえば、アセトヒドロキサム酸エチルに対して塩化ベンゼンスルホニルを用いてスルホニル化反応させることによって、合成することができる。
The O-benzenesulfonyl-acetohydroxamic acid ester derivative of the present invention has the following chemical formula:
It is represented by. The O-benzenesulfonyl-acetohydroxamic acid ester derivative can be synthesized, for example, by subjecting ethyl acetohydroxamic acid to sulfonylation using benzenesulfonyl chloride.
また、本発明のニトリル化合物合成試薬は、前記Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体を含むことを特徴とし、アルデヒド化合物からニトリル化合物を容易かつ高収率で合成することができる。 Moreover, the nitrile compound synthesis reagent of the present invention is characterized by containing the O-benzenesulfonyl-acetohydroxamic acid ester derivative, and can easily synthesize a nitrile compound from an aldehyde compound in a high yield.
さらに、本発明のニトリル化合物の製造方法は、本発明のニトリル化合物合成試薬、有機溶媒、酸触媒の存在下で、アルデヒド化合物をトランスオキシム化させる工程を含むことを特徴とする。 Furthermore, the method for producing a nitrile compound of the present invention includes a step of transoximing an aldehyde compound in the presence of the nitrile compound synthesis reagent of the present invention, an organic solvent, and an acid catalyst.
アルデヒド化合物はアルデヒド基を有する限り特に限定されないが、ベンズアルデヒド、トルアルデヒド、アニスアルデヒド、ナフトアルデヒド、フルオロベンズアルデヒド、クロロベンズアルデヒド、ブロモベンズアルデヒド、シンナムアルデヒド、トリフルオロトルアルデヒド、ニトロベンズアルデヒド、デカナール、フェニルプロピオンアルデヒド、フルフラール、トリフルオロトルアルデヒド、ニトロベンズアルデヒド、フェニルベンズアルデヒド、チオフェンカルボキシアルデヒド、イソブチルアルデヒドなどが挙げられる。これらのアルデヒド化合物から、対応するニトリル化合物を合成することができる。 The aldehyde compound is not particularly limited as long as it has an aldehyde group. , Trifluorotolualdehyde, nitrobenzaldehyde, phenylbenzaldehyde, thiophenecarboxaldehyde, isobutyraldehyde and the like. Corresponding nitrile compounds can be synthesized from these aldehyde compounds.
有機溶媒は特に限定されないが、塩化メチレン、クロロホルム、ヘキサン、トルエン、ジエチルエーテル、ヘキサン、トルエン、アセトニトリル、メタノール、テトラヒドロフラン、酢酸エチル、アセトン、ジメチルホルムアルデヒドなどが挙げられる。これらの有機溶媒は、２種以上を混合して使用することもできる。なかでも、反応収率の点で、塩化メチレン、クロロホルム、ヘキサン、トルエンなどが好ましい。 The organic solvent is not particularly limited, and examples include methylene chloride, chloroform, hexane, toluene, diethyl ether, hexane, toluene, acetonitrile, methanol, tetrahydrofuran, ethyl acetate, acetone, dimethylformaldehyde and the like. These organic solvents can be used in a mixture of two or more. Of these, methylene chloride, chloroform, hexane, toluene and the like are preferable from the viewpoint of reaction yield.
酸触媒は特に限定されないが、過塩素酸、トリフルオロメタンスルホン酸、ビストリフルオロメタンスルホンイミド、パラクロロベンゼンスルホン酸、ベンゼンスルホン酸、塩酸、硫酸、リン酸、硝酸などが挙げられる。これらの酸触媒は、２種以上を混合して使用することもできる。なかでも、反応収率の点で、トリフルオロメタンスルホン酸、ビストリフルオロメタンスルホンイミド、パラクロロベンゼンスルホン酸、ベンゼンスルホン酸が好ましい。 The acid catalyst is not particularly limited, and examples thereof include perchloric acid, trifluoromethanesulfonic acid, bistrifluoromethanesulfonimide, parachlorobenzenesulfonic acid, benzenesulfonic acid, hydrochloric acid, sulfuric acid, phosphoric acid, and nitric acid. These acid catalysts can be used in combination of two or more. Of these, trifluoromethanesulfonic acid, bistrifluoromethanesulfonimide, parachlorobenzenesulfonic acid, and benzenesulfonic acid are preferable in terms of reaction yield.
アルデヒド化合物に対するオキシム化合物の添加量は、アルデヒド化合物１モルに対して１〜５モルが好ましく、１〜２モルがより好ましい。１モル未満では、反応は完結しない。 The addition amount of the oxime compound relative to the aldehyde compound is preferably 1 to 5 mol, and more preferably 1 to 2 mol, relative to 1 mol of the aldehyde compound. If it is less than 1 mol, the reaction is not completed.
酸触媒の添加量は、アルデヒド化合物１モルに対して０．０１〜１モルが好ましく、０．０５〜０．１０モルがより好ましい。０．０１モル未満では、反応が完結しない傾向がある。 The addition amount of the acid catalyst is preferably 0.01 to 1 mol, more preferably 0.05 to 0.10 mol, relative to 1 mol of the aldehyde compound. If the amount is less than 0.01 mol, the reaction tends not to be completed.
反応温度は特に限定されないが、０〜４０℃が好ましく、２０〜３０℃がより好ましい。４０℃を超えると、溶媒が揮発する傾向がある。また、反応時間も特に限定されないが、１〜４８時間が好ましく、２４〜４８時間がより好ましい。１時間未満では、反応が完結しない傾向がある。 Although reaction temperature is not specifically limited, 0-40 degreeC is preferable and 20-30 degreeC is more preferable. When it exceeds 40 degreeC, there exists a tendency for a solvent to volatilize. Moreover, although reaction time is not specifically limited, 1 to 48 hours are preferable and 24 to 48 hours are more preferable. If it is less than 1 hour, the reaction tends to be incomplete.
本発明の製造方法によって得られたニトリル化合物は、医薬品、農薬、化粧品、香料およびそれらの原材料として有用である。 The nitrile compound obtained by the production method of the present invention is useful as pharmaceuticals, agricultural chemicals, cosmetics, fragrances and raw materials thereof.
以下、本発明の実施例について説明するが、本発明は、以下の実施例に限定されない。 Examples of the present invention will be described below, but the present invention is not limited to the following examples.
実施例１ Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エチル（２ａ）の合成
室温で、アルゴン雰囲気下、２０ｍＬフラスコ（撹拌子入）に アセトヒドロキサム酸エチル（２００ｍｇ、１．９４ｍｍｏｌ、１．０ｅｑ．）、塩化ベンゼンスルホニル（０．３３ｍＬ、２．６２ ｍｍｏｌ、１．３５ｅｑ．）、トリエチルアミン（０．３９ｍＬ、２．８１ｍｍｏｌ、１．４５ｅｑ．）、テトラヒドロフラン（６．４ｍＬ、０．３０Ｍ）を加え、室温で１時間、撹拌した。その後、飽和塩化アンモニウム水溶液で反応を停止し、テトラヒドロフランを減圧留去後に、ジエチルエーテル（２０ｍＬ×３回）を用いて抽出を行い、有機相を飽和食塩水で洗浄後、硫酸ナトリウムを用いて乾燥した。硫酸ナトリウムを綿栓濾過で濾別し、減圧下溶媒を留去してＮＭＲ（ＣＤＣｌ３）を測定した。シリカゲルカラムクロマトグラフィー（関東化学 ｓｉｌｉｃａ ｇｅｌ ６０（４０−５０μｍ）、ヘキサン／酢酸エチル＝９５／５）で精製し、白色のＯ−ベンゼンスルホニル−アセトヒドロキサム酸エチル（化合物２ａ）を３７６ｍｇ（収率８０％）得た。化合物２ａのＮＭＲデータは、以下の通りである。
Example 1 Synthesis of ethyl O-benzenesulfonyl-acetohydroxamate (2a) In a 20 mL flask (with stir bar) at room temperature under argon atmosphere, ethyl acetohydroxamate (200 mg, 1.94 mmol, 1.0 eq). ), Benzenesulfonyl chloride (0.33 mL, 2.62 mmol, 1.35 eq.), Triethylamine (0.39 mL, 2.81 mmol, 1.45 eq.), Tetrahydrofuran (6.4 mL, 0.30 M) were added. And stirred at room temperature for 1 hour. Thereafter, the reaction was stopped with a saturated aqueous ammonium chloride solution, and tetrahydrofuran was distilled off under reduced pressure, followed by extraction with diethyl ether (20 mL × 3 times). The organic phase was washed with saturated brine and then dried with sodium sulfate. did. Sodium sulfate was filtered off by cotton plug filtration, the solvent was distilled off under reduced pressure, and NMR (CDCl 3 ) was measured. Purification by silica gel column chromatography (Kanto Chemical Silica gel 60 (40-50 μm), hexane / ethyl acetate = 95/5) gave 376 mg (yield 80) of white O-benzenesulfonyl-acetohydroxamic acid ethyl (compound 2a). %)Obtained. The NMR data of compound 2a are as follows.
２ａ：１Ｈ−ＮＭＲ（４００Ｈｚ、ＣＤＣｌ３）δ１．２２（ｔ，Ｊ＝７．１Ｈｚ，３Ｈ），２．０２（ｓ，３Ｈ），３．９７（ｑ，Ｊ＝７．１Ｈｚ，２Ｈ），７．５４（ｄ，Ｊ＝７．５Ｈｚ，２Ｈ），７．６７（ｄ，Ｊ＝７．５Ｈｚ，１Ｈ），７．９７（ｄ，Ｊ＝７．５Ｈｚ，２Ｈ）；１３Ｃ−ＮＭＲ（ＣＤＣｌ３，１００ＭＨｚ）δ１４．８，１５．８，６４．７，１２９．６，１３４．６，１３６．３，１７０．８． 2a: 1 H-NMR (400 Hz, CDCl 3 ) δ 1.22 (t, J = 7.1 Hz, 3H), 2.02 (s, 3H), 3.97 (q, J = 7.1 Hz, 2H) , 7.54 (d, J = 7.5 Hz, 2H), 7.67 (d, J = 7.5 Hz, 1H), 7.97 (d, J = 7.5 Hz, 2H); 13 C-NMR (CDCl 3 , 100 MHz) δ 14.8, 15.8, 64.7, 129.6, 134.6, 136.3, 170.8.
実施例２ Ｏ−パラメトキシベンゼンスルホニル−アセトヒドロキサム酸エチル（２ｊ）の合成
室温で、アルゴン雰囲気下、２０ｍＬフラスコ（撹拌子入）にアセトヒドロキサム酸エチル（２００ｍｇ，１．９４ｍｍｏｌ，１．０ｅｑ．）、塩化パラメトキシベンゼンスルホニル（６４１ｍｇ、 ２．６２ｍｍｏｌ、１．３５ｅｑ．）、トリエチルアミン（０．３９ｍＬ，２．８１ｍｍｏｌ，１．４５ｅｑ．）、テトラヒドロフラン（６．４ ｍＬ，０．３０Ｍ）を加え、室温で３時間撹拌した。その後、パラジメチルアミノピリジン（２３．７ｍｇ，０．１９４ｍｍｏｌ，０．１０ｅｑ．）を加え、３ 時間撹拌し、飽和塩化アンモニウム水溶液で反応を停止し、テトラヒドロフランを減圧留去後に、ジエチルエーテル（２０ｍＬ×３回）を用いて抽出を行い、有機相を飽和食塩水で洗浄後、硫酸ナトリウムを用いて乾燥した。硫酸ナトリウムを綿栓濾過で濾別し、減圧下溶媒を留去してＮＭＲ（ＣＤＣｌ３）を測定した。シリカゲルカラムクロマトグラフィー（関東化学 ｓｉｌｉｃａ ｇｅｌ ６０（４０−５０μｍ）、ヘキサン／ 酢酸エチル＝８０／２０）で精製し、白色のＯ−パラメトキシベンゼンスルホニル−アセトヒドロキサム酸エチル（化合物２ｊ）を２９５ｍｇ（収率５６％）得た。化合物２ｊのＮＭＲデータは、以下の通りである。
Example 2 Synthesis of ethyl O-paramethoxybenzenesulfonyl-acetohydroxamate (2j) In a 20 mL flask (with stir bar) at room temperature under argon atmosphere, ethyl acetohydroxamate (200 mg, 1.94 mmol, 1 0.0 eq.), Paramethoxybenzenesulfonyl chloride (641 mg, 2.62 mmol, 1.35 eq.), Triethylamine (0.39 mL, 2.81 mmol, 1.45 eq.), Tetrahydrofuran (6.4 mL, 0.30 M) And stirred at room temperature for 3 hours. Thereafter, paradimethylaminopyridine (23.7 mg, 0.194 mmol, 0.10 eq.) Was added and stirred for 3 hours. The reaction was stopped with a saturated aqueous ammonium chloride solution, and tetrahydrofuran was distilled off under reduced pressure. The organic phase was washed with a saturated saline solution and dried using sodium sulfate. Sodium sulfate was filtered off by cotton plug filtration, the solvent was distilled off under reduced pressure, and NMR (CDCl 3 ) was measured. Purification by silica gel column chromatography (Kanto Chemical Silica Gel 60 (40-50 μm), hexane / ethyl acetate = 80/20) gave 295 mg (yield of white O-paramethoxybenzenesulfonyl-acetohydroxamic acid ethyl (compound 2j)). Rate 56%). The NMR data of compound 2j are as follows.
２ｊ：１Ｈ−ＮＭＲ（４００Ｈｚ，ＣＤＣｌ３）δ１．２２（ｔ，Ｊ＝７．１Ｈｚ，３Ｈ），２．０１（ｓ，３Ｈ），２．０３（ｓ，３Ｈ），４．０２（ｑ，Ｊ＝７．１Ｈｚ，２Ｈ），６．９９（ｄ，Ｊ＝８．８Ｈｚ，１Ｈ），７．９１（ｄ，Ｊ＝８．８Ｈｚ，２Ｈ）；１３Ｃ−ＮＭＲ（ＣＤＣｌ３，１００ＭＨｚ，ｐｐｍ）δ１４．７，１５．６，５６．４，６３．８，６４．５，１１４．８，１３１．８，１６４．７，１７０．５． 2j: 1 H-NMR (400 Hz, CDCl 3 ) δ 1.22 (t, J = 7.1 Hz, 3H), 2.01 (s, 3H), 2.03 (s, 3H), 4.02 (q , J = 7.1 Hz, 2H), 6.99 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.8 Hz, 2H); 13 C-NMR (CDCl 3 , 100 MHz, ppm) δ 14.7, 15.6, 56.4, 63.8, 64.5, 114.8, 131.8, 164.7, 170.5.
実施例３ Ｏ−パラトリフルオロメチルベンゼンスルホニル−アセトヒドロキサム酸エチル（２ｋ）の合成
室温で、アルゴン雰囲気下、２０ｍＬフラスコ（撹拌子入）にアセトヒドロキサム酸エチル（２００ｍｇ，１．９４ ｍｍｏｌ，１．０ ｅｑ．）、塩化パラトリフルオロメチルベンゼンスルホニル（６４０ｍｇ，２．６２ｍｍｏｌ，１．３５ｅｑ．）、トリエチルアミン（０．３９ｍＬ，２．８１ ｍｍｏｌ，１．４５ｅｑ．）、テトラヒドロフラン（６．４ｍＬ，０．３０Ｍ）を加え、室温で１時間撹拌した。その後、飽和塩化アンモニウム水溶液で反応を停止し、テトラヒドロフランを減圧留去後に、ジエチルエーテル（２０ｍＬ×３回）を用いて抽出を行い、有機相を飽和食塩水で洗浄後、硫酸ナトリウムを用いて乾燥した。硫酸ナトリウムを綿栓濾過で濾別し、減圧下溶媒を留去してＮＭＲ（ＣＤＣｌ３）を測定した。シリカゲルカラムクロマトグラフィー（関東化学 ｓｉｌｉｃａ ｇｅｌ ６０（４０−５０μｍ）、ヘキサン／ジエチルエーテル＝９０／１０）で精製し、白色のＯ−パラトリフルオロメチルベンゼンスルホニル−アセトヒドロキサム酸エチル（化合物２ｋ）を５３３ｍｇ（収率８８％）得た。化合物２ｋのＮＭＲデータは、以下の通りである。
Example 3 Synthesis of ethyl O-paratrifluoromethylbenzenesulfonyl-acetohydroxamic acid (2k) In a 20 mL flask (with stirring bar) at room temperature under argon atmosphere, ethyl acetohydroxamic acid (200 mg, 1.94). mmol, 1.0 eq.), paratrifluoromethylbenzenesulfonyl chloride (640 mg, 2.62 mmol, 1.35 eq.), triethylamine (0.39 mL, 2.81 mmol, 1.45 eq.), tetrahydrofuran (6. 4 mL, 0.30 M) was added, and the mixture was stirred at room temperature for 1 hour. Thereafter, the reaction was stopped with a saturated aqueous ammonium chloride solution, and tetrahydrofuran was distilled off under reduced pressure, followed by extraction with diethyl ether (20 mL × 3 times). The organic phase was washed with saturated brine and then dried with sodium sulfate. did. Sodium sulfate was filtered off by cotton plug filtration, the solvent was distilled off under reduced pressure, and NMR (CDCl 3 ) was measured. Purification by silica gel column chromatography (Kanto Chemical Silica Gel 60 (40-50 μm), hexane / diethyl ether = 90/10) and 533 mg of white O-paratrifluoromethylbenzenesulfonyl-acetohydroxamic acid ethyl (compound 2k) (Yield 88%). The NMR data of compound 2k are as follows.
２ｋ：１Ｈ−ＮＭＲ（４００Ｈｚ，ＣＤＣｌ３）δ１．２６（ｔ，Ｊ＝７．１Ｈｚ，３Ｈ），２．０５（ｓ，３Ｈ），３．９７（ｑ，Ｊ＝７．１Ｈｚ，２Ｈ），７．８２（ｄ，Ｊ＝８．３Ｈｚ，２Ｈ），８．１１（ｄ，Ｊ＝８．３Ｈｚ，２Ｈ）；１９Ｆ−ＮＭＲ（３７６ＭＨｚ，ＣＤＣｌ３）δ−６３．５（ｓ，１Ｆ）；１３Ｃ−ＮＭＲ（ＣＤＣｌ３，１００ＭＨｚ）δ１４．８，１６．０，６４．９，１２４．０（ｑ，ＪＣ−Ｆ＝２７１．８Ｈｚ），１２６．８（ｑ，ＪＣ−Ｆ＝３．８２Ｈｚ），１３０．４，１３６．３（ｑ，ＪＣ−Ｆ＝３２．９Ｈｚ），１３９．９（ｄ，ＪＣ−Ｆ＝１．４３Ｈｚ），１７１．１． 2k: 1 H-NMR (400 Hz, CDCl 3 ) δ 1.26 (t, J = 7.1 Hz, 3H), 2.05 (s, 3H), 3.97 (q, J = 7.1 Hz, 2H) , 7.82 (d, J = 8.3 Hz, 2H), 8.11 (d, J = 8.3 Hz, 2H); 19 F-NMR (376 MHz, CDCl 3 ) δ-63.5 (s, 1F ); 13 C-NMR (CDCl 3 , 100 MHz) δ 14.8, 16.0, 64.9, 124.0 (q, JC-F = 271.8 Hz), 126.8 (q, JC-F = 3) .82 Hz), 130.4, 136.3 (q, JC-F = 32.9 Hz), 139.9 (d, JC-F = 1.43 Hz), 171.1.
実施例４ Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エチル（化合物２ａ）を用いた２−ナフトニトリル（化合物３ａ）の合成
室温で、アルゴン雰囲気下、試験管（撹拌子入）にアルデヒド化合物として２−ナフトアルデヒド（５３．２ｍｇ，０．３４０ｍｍｏｌ，１．０ｅｑ．）、触媒となる過塩素酸水溶液（７０ｗｔ％，１．５μＬ，０．０１７０ｍｍｏｌ，５ｍｏｌ％）、塩化メチレン（０．６８ｍＬ，０．５０Ｍ）、Ｏ−ベンゼンスルホニル−アセトヒドロキサム酸エチル（８６．９ｍｇ，０．３５７ｍｍｏｌ，１．０５ｅｑ．）を加え、室温で２４時間撹拌した。その後、塩化メチレン２０ｍｌを加え、反応液をシリカゲルパッドに通して減圧濾過し、溶媒を留去してＮＭＲを測定した。シリカゲルカラムクロマトグラフィー（関東化学 ｓｉｌｉｃａ ｇｅｌ ６０（４０−５０μｍ）、ヘキサン／ジエチルエーテル＝９／１）で精製し、白色の２−ナフトニトリル（化合物３ａ）を５２．０ｍｇ（収率９９％）を得た。化合物３ａのＮＭＲデータは、以下の通りである。
Example 4 Synthesis of 2-naphthonitrile (Compound 3a) using ethyl O-benzenesulfonyl-acetohydroxamic acid (Compound 2a) An aldehyde compound in a test tube (with stirring bar) at room temperature under an argon atmosphere 2-naphthaldehyde (53.2 mg, 0.340 mmol, 1.0 eq.), Perchloric acid aqueous solution (70 wt%, 1.5 μL, 0.0170 mmol, 5 mol%) as a catalyst, methylene chloride (0.68 mL, 0.50M) and ethyl O-benzenesulfonyl-acetohydroxamic acid (86.9 mg, 0.357 mmol, 1.05 eq.) Were added, and the mixture was stirred at room temperature for 24 hours. Thereafter, 20 ml of methylene chloride was added, the reaction solution was filtered through a silica gel pad under reduced pressure, the solvent was distilled off, and NMR was measured. Purification by silica gel column chromatography (Kanto Chemical Silica Gel 60 (40-50 μm), hexane / diethyl ether = 9/1) gave 52.0 mg (99% yield) of white 2-naphthonitrile (Compound 3a). Obtained. The NMR data of compound 3a are as follows.
３ａ：１Ｈ−ＮＭＲ（ＣＤＣｌ３，４００ＭＨｚ，ｐｐｍ）δ７．５９−７．６７（ｍ，３Ｈ），７．８９−７．９３（ｍ，３Ｈ），８．２４（ｓ，１Ｈ）；１３Ｃ−ＮＭＲ（ＣＤＣｌ３，１００ＭＨｚ，ｐｐｍ）δ１０９．３，１１９．２，１２６．２，１２７．６，１２７．９，１２８．３，１２８．９，１２９．０，１３２．１，１３４．０，１３４．５． 3a: 1 H-NMR (CDCl 3 , 400 MHz, ppm) δ 7.59-7.67 (m, 3H), 7.89-7.93 (m, 3H), 8.24 (s, 1H); 13 C-NMR (CDCl 3 , 100 MHz, ppm) δ 109.3, 119.2, 126.2, 127.6, 127.9, 128.3, 128.9, 129.0, 132.1, 134.0 134.5.
本発明のニトリル化合物合成試薬を使用したニトリル化合物の製造方法を利用して合成したニトリル類を、反応条件と収率とともに以下に示す。 Nitriles synthesized using the method for producing a nitrile compound using the nitrile compound synthesis reagent of the present invention are shown below together with reaction conditions and yields.
電子供与性置換基や電子求引性置換基を有する芳香族アルデヒドに対しては、高収率で反応が進行した（３ｅ、３ｈ、３ｉ）。ハロゲンを有する芳香族アルデヒド類はいずれも良好な反応性を示し（３ｊ−３ｎ）、置換基の位置についてはパラ、メタ、オルト位ともに高収率で目的物が得られた（３ｅ−３ｇ、３ｋ−３ｍ）。ヘテロ環についても高い反応性を示した（３ｐ−３ｓ）。不飽和アルデヒドについてはマイケル付加反応が副反応として想定されたが、目的物のみが選択的に得られた（３ｔ）。直鎖やα位に分岐構造を有する脂肪族アルデヒドに関しても首尾よく反応が進行した（３ｕ−３ｘ）。 For aromatic aldehydes having an electron donating substituent or an electron withdrawing substituent, the reaction proceeded in high yield (3e, 3h, 3i). All of the aromatic aldehydes having halogen showed good reactivity (3j-3n), and the target product was obtained in high yield in the para, meta, and ortho positions (3e-3g, 3k-3m). The heterocycle also showed high reactivity (3p-3s). For unsaturated aldehydes, Michael addition reaction was assumed as a side reaction, but only the desired product was selectively obtained (3t). Reactions also proceeded successfully for linear aldehydes and aliphatic aldehydes having a branched structure at the α-position (3u-3x).
実施例５
表１に保護基ＰＧを変更した合成試薬の検討結果を示す。芳香族スルホニル基を有するオキシムにて良好な結果が得られることが分かり、なかでもベンゼンスルホニル基や４−トリフルオロメチルベンゼンスルホニル基が最も優れた結果を示すことが分かる（Ｅｎｔｒｙ４〜６参照）。
Example 5
Table 1 shows the results of studies on synthetic reagents in which the protecting group PG was changed. It turns out that a favorable result is obtained with the oxime which has an aromatic sulfonyl group, and it turns out that a benzenesulfonyl group and 4-trifluoromethylbenzenesulfonyl group show the most excellent result (refer to Entry 4-6).
実施例６
表２は、２−ナフトアルデヒドから２−ナフトニトリルを合成する反応における種々の触媒を検討した結果を示す。触媒には過塩素酸、トリフルオロメタンスルホン酸、ビストリフルオロメタンスルホンイミド、パラクロロベンゼンスルホン酸、ベンゼンスルホン酸が最も優れた結果を示すことが分かる（エントリー８、９、１０、１２、１３参照）。
Example 6
Table 2 shows the results of examining various catalysts in the reaction for synthesizing 2-naphthonitrile from 2-naphthaldehyde. As the catalyst, it can be seen that perchloric acid, trifluoromethanesulfonic acid, bistrifluoromethanesulfonimide, parachlorobenzenesulfonic acid, and benzenesulfonic acid show the best results (see entries 8, 9, 10, 12, 13).
実施例７
その他の溶媒の検討を行った（表３）。塩化メチレン、クロロホルム、ヘキサン、トルエンが最適であることが分かった（エントリー１７、１８、２０、２１参照）。
Other solvents were examined (Table 3). Methylene chloride, chloroform, hexane and toluene were found to be optimal (see entries 17, 18, 20, 21).
本発明によれば、ヒドロキシルアミン等価体としてオキシム化合物を扱うことができるため、温和な反応条件で、高収率でアルデヒドからニトリル化合物を得ることができる。また、得られたニトリル化合物は、医薬品、農薬、化粧品、香料及びそれらの原材料として有用である。 According to the present invention, since an oxime compound can be handled as a hydroxylamine equivalent, a nitrile compound can be obtained from an aldehyde in a high yield under mild reaction conditions. Moreover, the obtained nitrile compound is useful as a pharmaceutical, an agricultural chemical, cosmetics, a fragrance | flavor, and those raw materials.
Claims (5)
で表されるＯ−ベンゼンスルホニル−アセトヒドロキサム酸エステル誘導体。 The following chemical formula
An O-benzenesulfonyl-acetohydroxamic acid ester derivative represented by:
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| JP2019142803A (en) * | 2018-02-20 | 2019-08-29 | 学校法人 龍谷大学 | Production method of primary amine compound |
| CN118388372A (en) * | 2024-04-23 | 2024-07-26 | 辽宁众辉生物科技有限公司 | Efficient green synthesis method of 2-methyl-alpha-hydroxyiminobenzyl cyanide |
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| JP2019142803A (en) * | 2018-02-20 | 2019-08-29 | 学校法人 龍谷大学 | Production method of primary amine compound |
| JP7031858B2 (en) | 2018-02-20 | 2022-03-08 | 学校法人 龍谷大学 | Method for producing primary amine compound |
| CN118388372A (en) * | 2024-04-23 | 2024-07-26 | 辽宁众辉生物科技有限公司 | Efficient green synthesis method of 2-methyl-alpha-hydroxyiminobenzyl cyanide |
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