WO2003035605A1 - Nouveaux composes et procede de production associe - Google Patents

Nouveaux composes et procede de production associe Download PDF

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Publication number
WO2003035605A1
WO2003035605A1 PCT/JP2002/011054 JP0211054W WO03035605A1 WO 2003035605 A1 WO2003035605 A1 WO 2003035605A1 JP 0211054 W JP0211054 W JP 0211054W WO 03035605 A1 WO03035605 A1 WO 03035605A1
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WIPO (PCT)
Prior art keywords
group
general formula
compound
reaction
crude product
Prior art date
Application number
PCT/JP2002/011054
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English (en)
Japanese (ja)
Inventor
Hisao Nemoto
Original Assignee
Techno Network Shikoku Co., Ltd.
Eisai Co., Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Techno Network Shikoku Co., Ltd., Eisai Co., Ltd. filed Critical Techno Network Shikoku Co., Ltd.
Priority to JP2003538121A priority Critical patent/JP4163113B2/ja
Publication of WO2003035605A1 publication Critical patent/WO2003035605A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/16—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same carbon atom of an acyclic carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages
    • C07F7/1872—Preparation; Treatments not provided for in C07F7/20
    • C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages

Definitions

  • the present invention relates to a compound useful as a carbon addition reagent, and a method for efficiently producing the compound.
  • Conventional technology
  • the compounds represented by the following general formulas react with various electrophiles to arrange an acyl cyanide functional group together with a one-carbon enrichment, and also react with various nucleophiles. It is known to have high applicability to compound synthesis (Hisao Nemoto; Yasufumi Kubota; Yoshinori Yamamoto, J. Org. Chem., 55, 4515-4516, 1990.),
  • R represents R′R 2 R 3 Si—, R′0-CR 2 R 3 — (R 2 and R 3 are monovalent hydrocarbon groups).
  • R represents R′R 2 R 3 Si—, R′0-CR 2 R 3 — (R 2 and R 3 are monovalent hydrocarbon groups).
  • the above synthesis method requires as many as six steps, includes a step requiring a reaction time of 2 weeks or more (fifth step), and requires an expensive condensing agent (sixth step). There was a problem that the total yield was not sufficient (about 10%), and improvement was required.
  • those obtained by the above synthesis method are limited to those in which R is an organic silicon type (RiR 3 Si—) or a monoalkoxyalkyl group type (O—CR 2 R 3 —).
  • R is an organic silicon type
  • R'CO- alkanoyl group
  • compounds in which R is an alkanoyl group (R'CO-) are expected to have other applications than those of the above-mentioned organosilicon type or 1-alkoxyalkyl group type, but such compounds are still provided.
  • R'CO- alkanoyl group
  • the above synthesis reaction involves a process using ammonia in the fifth step, and the R'CO bond is cleaved by the decomposition of the processing compound, resulting in extremely difficult synthesis.
  • the present invention has been made in view of the above problems of the related art, and has as its object to provide a method for efficiently producing a compound useful as a carbon addition reagent represented by the above general formula, and to provide a novel carbon addition reagent compound.
  • the present inventors have conducted intensive studies to achieve such an object, and as a result, have found a method for obtaining the above compound in a two-step reaction step by a specific method, and have completed the present invention.
  • the present invention provides a compound represented by the following general formula (1)
  • R ′′ represents an alkyl group or an aryl group.
  • Oxidative cleavage reaction is carried out by adding peracetic acid to the crude product, and a hydroxyl group in the obtained crude product is subjected to a protection reaction by adding a protecting reagent to the resulting compound to obtain a compound represented by the following general formula (2).
  • R represents a monovalent organic group or an organic metal group.
  • R 1 represents a monovalent hydrocarbon group.
  • the present invention further provides a method for producing a compound represented by the following general formula (2), which comprises reacting a hydroxyl group in the obtained crude product with a protecting reagent to carry out a protection reaction.
  • R represents R iRSRSS i, shaku 1.
  • R 1 R 2 and R 3 are each independently a hydrogen atom, an alkyl group, C 6 - 14 show a Teroari Ichiru group to ⁇ Li Ichiru group or 5-14 membered).
  • R is preferably a methyl group.
  • R is an acetyl group, n C ⁇ Hs 3 —CO—, a benzoyl group, a t-butyldimethylsilyl group or a compound represented by the formula
  • the present invention provides a compound represented by the following general formula (3).
  • R 1 represents a hydrogen atom, CI- 3 alkyl group, C 6 -.. Shows the Teroariru group to 14 Ariru group or 5-1 4 membered
  • scale 1 is preferably an acetyl group, nCnH—CO— or a benzoyl group.
  • R represents a monovalent organic group or an organometallic group, and more specifically, R i Si-, R'0-CR 2 R 3- , or ⁇ CO— (R ', R 2 R 3 is a monovalent hydrocarbon group such as an alkyl group and an aryl group), but is not limited thereto.
  • the reaction formula in the production method of the present invention is represented as follows.
  • R in the general formula is the starting material in the production method of the present invention (1) "(HO) OC (CN smell Te, R” represents an alkyl group or Ariru group, from easy availability, CH 3, Eta 5 It is preferable to use, and particularly preferably. Regardless of which R "is used, the reaction mechanism itself is the same,
  • This oxidative cleavage reaction may be performed at room temperature.
  • a compound (protecting reagent) corresponding to a desired R such as acetyl chloride, benzoyl chloride, dodecanol chloride, tert-butychlorodimethylsilane, ethyl vinyl ether, and pyridines are formed in the obtained crude product.
  • a desired R such as acetyl chloride, benzoyl chloride, dodecanol chloride, tert-butychlorodimethylsilane, ethyl vinyl ether, and pyridines are formed in the obtained crude product.
  • the reaction may be carried out for several minutes to several tens of hours.
  • the desired product can be obtained by performing appropriate known purification as necessary.
  • Alkyl group refers to a monovalent group derived from an aliphatic hydrocarbon having 1 to 30 carbon atoms by removing one hydrogen atom. 1-30 straight or branched alkyl groups are meant. In the “(: 30 alkyl group)”, “dialkyl group” is preferable.
  • the “u alkyl group” is specifically, for example, a methyl group, an ethyl group, a monopropyl group, a 2-propyl group, a 2-methyl-1-propyl group, a 2-methyl-2-propyl group, a monobutyl group, _Ndenyl group ( ⁇ ⁇ ⁇ 23 ⁇ ) and the like.
  • the “C 6-14 aryl group” represented in the present specification means an aromatic hydrocarbon cyclic group having 6 to 14 carbon atoms.
  • the rather preferable in the "C 6 _ 14 Ariru group” is a "C 6 _ 10 Ariru group”. This particular 'specifically the “C 6 _ 10 Ariru group” for example, phenyl group, 1 one naphthyl, 2-naphthyl group.
  • the “5- to 14-membered heteroaryl group” represented in the present specification means that the number of atoms constituting the ring of the cyclic group is 5 to 14, and one of the atoms constituting the ring of the cyclic group is 1 Means an aromatic cyclic group containing a plurality of heteroatoms.
  • the “5- to 14-membered heteroaryl group” is preferably a “5- to 10-membered heteroaryl group”.
  • the “5- to 10-membered heteroaryl group” means a monovalent group derived from the “5- to 10-membered aromatic heterocycle” by removing one hydrogen atom at an arbitrary position.
  • This “5- to 10-membered aromatic heterocycle” means that the number of atoms constituting the ring of the cyclic group is 5 to 10, and one to a plurality of atoms constitute the ring of the cyclic group.
  • protecting reagent refers to a reagent generally used for adding a protecting group to a hydroxyl group, and specifically includes, for example, acetyl chloride, benzoyl chloride, dodecanoyl chloride, and the like. Acid anhydrides such as acetic anhydride; vinyl ether compounds such as ethyl vinyl ether; and silylating reagents such as tert-butylcyclodimethyldimethylsilane.
  • the term "protecting reagent” include, for example, acetyl chloride, benzoyl chloride, dodecanoyl chloride, ethyl vinyl ether and t-butylchlorodimethylsilane.
  • the term "protection reaction” refers to a reaction in which a compound having a hydroxyl group is reacted with a protective reagent under appropriate conditions to introduce a protective group into the hydroxyl group.
  • a protecting group can be introduced into a hydroxyl group under conditions generally used for introducing a protecting group, depending on the protecting reagent used in the reaction.
  • a base or an acid can be added. Examples of the base include imidazole, pyridine, 4-dimethylaminopyridine (DMAP) and the like, and examples of the acid include 4-toluenesulfonic acid.
  • DMAP 4-dimethylaminopyridine
  • H 3 C (HO) C C (CN) 2 (202 mg, 1.87 t ol) in aqueous solution (4 mL) with peracetic acid (3% of 9% acetic acid solution, 3.74 t ol) at room temperature And stirred at room temperature for 4 hours.
  • the resulting reaction solution was mixed with acetyl chloride (12 mL, 12.7 rol), 4- (N, N-dimethylamino) pyridine (23 mg, 0.19 mmol) and stirred at room temperature for 5 minutes.
  • Benzoyl chloride (271 mg, 1.93 IMO1) and pyridine (168 mg, 0.17 mL, 2.13 dragonol) were added dropwise to this solution at 0 ° C, and the mixture was stirred at 0 ° C for 5 minutes, and then acetonitrile was removed under reduced pressure.
  • the residue was diluted with 30 mL of ethyl acetate, washed with a saturated aqueous solution of sodium hydrogencarbonate (3 times with 15 mL), and a saturated saline solution (1 time with 15 mL), dried over magnesium sulfate, concentrated under reduced pressure, and concentrated under reduced pressure.
  • H 3 C (HO) C C (CN) 2 (208 mg, 1, 93 bandol) in methanol (lOmL) and peracetic acid (5 mL of 9% acetic acid solution, equivalent to 6.04 bandol) at room temperature And stirred at room temperature for 2 hours. To the reaction mixture was further added peracetic acid (9% acetic acid solution was 1111.24, 0 target) at room temperature, and stirring was continued at room temperature for 2 hours. The obtained reaction solution was concentrated under reduced pressure while keeping the temperature at 35 ° C. or lower, and the residue was dissolved in 5 mL of dichloromethane.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne des composés de formule générale RO-CH(CN)2, dans laquelle R représente un groupe organique monovalent. Ces composés peuvent être utilisés en tant que réactifs à addition de carbone, et ils peuvent être produits de manière efficace, à haut rendement. L'invention concerne en particulier un procédé de production de composés de formule générale (2), dans laquelle R représente un groupe organique ou organométallique monovalent, ces composés se caractérisant par l'ajout d'acide péracétique à un composé de formule générale (1 ), dans laquelle R'' représente alkyle ou aryle. Le procédé consiste ensuite à brasser le mélange résultant pour réaliser un clivage oxydant, et à ajouter un réactif protecteur d'hydroxyle au produit brut obtenu, pour protéger le groupe hydroxyle.
PCT/JP2002/011054 2001-10-24 2002-10-24 Nouveaux composes et procede de production associe WO2003035605A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2003538121A JP4163113B2 (ja) 2001-10-24 2002-10-24 新規化合物及びその製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001-326484 2001-10-24
JP2001326484 2001-10-24

Publications (1)

Publication Number Publication Date
WO2003035605A1 true WO2003035605A1 (fr) 2003-05-01

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JP (1) JP4163113B2 (fr)
WO (1) WO2003035605A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006104148A (ja) * 2004-10-07 2006-04-20 Techno Network Shikoku Co Ltd シアノ化合物の安全かつ効率的な製造方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI428682B (zh) 2005-03-22 2014-03-01 Kuraray Co 成型薄片及柱狀透鏡薄片之製造方法、以及其等之製造裝置

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2807935A1 (de) * 1978-02-24 1979-08-30 Hoechst Ag Verfahren zur herstellung von gemischen aus dichloressigsaeure- (1-cyan-2,2-dichlor)-vinylester und 2-dichlormethyl-2-dichloracetoxy- malonsaeuredinitril
JPH05119486A (ja) * 1991-10-25 1993-05-18 Fuji Photo Film Co Ltd 電子写真式平版印刷版の製造方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2807935A1 (de) * 1978-02-24 1979-08-30 Hoechst Ag Verfahren zur herstellung von gemischen aus dichloressigsaeure- (1-cyan-2,2-dichlor)-vinylester und 2-dichlormethyl-2-dichloracetoxy- malonsaeuredinitril
JPH05119486A (ja) * 1991-10-25 1993-05-18 Fuji Photo Film Co Ltd 電子写真式平版印刷版の製造方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LEV I.J. ET AL.: "Photogeneration and reactions of acyclic carbonyl ylides", JOURNAL OF ORGANIC CHEMISTRY, vol. 41, no. 15, 1976, pages 2654 - 2656, XP002961082 *
NEMOTO HISAO; KUBOTA ET AL.: "Development of a new acyl anion equivalent for the preparation of masked activated esters and their use to prepare a dipeptide", JOURNAL OF ORGANIC CHEMISTRY, vol. 55, no. 15, 1990, pages 4515 - 4516, XP002165046 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006104148A (ja) * 2004-10-07 2006-04-20 Techno Network Shikoku Co Ltd シアノ化合物の安全かつ効率的な製造方法
JP4691629B2 (ja) * 2004-10-07 2011-06-01 株式会社テクノネットワーク四国 シアノ化合物の安全かつ効率的な製造方法

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Publication number Publication date
JP4163113B2 (ja) 2008-10-08
JPWO2003035605A1 (ja) 2005-02-10

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