JP2005068102A - Method for producing cyclic ketone - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for easily producing a cyclic ketone useful as a synthetic intermediate for pharmaceuticals, agrochemicals, a ligand for olefin polymerization catalyst and a liquid crystal material in high yield at a low cost while suppressing the generation of chemical substances causing environmental pollution. <P>SOLUTION: A cyclic ketone expressed by a specific chemical formula is produced by reacting a carboxylic acid expressed by general formula (I) with a catalytic amount of a Lewis acid expressed by general formula (II): MXm-Ln. In general formula (I), R<SP>1</SP>to R<SP>4</SP>are each a univalent group; and the ring A is a monocyclic or condensed polycyclic aromatic group or heteroaromatic group optionally containing N, O or S atom as the atom constituting the ring. In general formula (II), M is a metal ion selected from Bi, Ga, In, Hf and rare-earth elements; X is an anion selected from halogens, perfluoroalkylsulfonates, bis(perfluoroalkylsulfonyl) amides and tris(perfluoroalkylsulfonyl) methide; and L is a neutral molecule having coordinating power. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

   The present invention relates to a method for producing a cyclic ketone useful as a pharmaceutical or agricultural chemical, a ligand for an olefin polymerization catalyst, or a synthetic intermediate for a liquid crystal material.

  Many methods for producing cyclic ketones by intramolecular cyclization of 3-arylpropionic acids have been reported. However, these methods usually employ a two-stage method in which carboxylic acid is once converted into an acid chloride and then cyclized with aluminum chloride or the like (see Patent Document 1-2). In addition, production methods in which 3-arylpropionic acids are directly subjected to a dehydration cyclization reaction have been reported. However, since all of these methods require an excess amount of an acid reactant of 1 equivalent or more, a large amount of waste acid is generated. Have a problem. For example, polyphosphoric acid (see Patent Document 3, Non-Patent Documents 1 and 2), methanesulfonic acid (see Non-Patent Document 3), and methanesulfonic acid-phosphorus pentoxide mixture (see Non-Patent Documents 2 and 4) are used in an amount of solvent. The method is known. More recently, although there is a report that zeolite has a catalytic action in the cyclization reaction (see Non-Patent Document 5), there is a disadvantage that the yield of the target product is low.

Japanese Patent Laid-Open No. 10-273474 US2003 / 0009046A1 Japanese Patent Laid-Open No. 10-324648 Ber. Deutsch. Chem. Ges. 56, p620 (1923) Heterocycles 43, p127 (1996) J. et al. Org. Chem. 46, p2974 (1981) J. et al. Org. Chem. 38, p4071 (1973) J. et al. Inclusion Phenom. Macrocyclic Chem. 45, p41 (2003)

  The present invention has been made to solve the above-described problems in the prior art. That is, the object of the present invention is to reduce the production of chemical ketones that cause environmental pollution by reducing the use of chemicals and agricultural chemicals, ligands for olefin polymerization catalysts, and cyclic ketones that are useful as synthetic intermediates for liquid crystal materials. It is another object of the present invention to provide a method that can be obtained in a high yield.

  As a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention have made it possible to rapidly carry out the dehydration cyclization reaction of propionic acids in which the 3-position is substituted with an aromatic ring by adding a small amount of a certain Lewis acid. It has been found that cyclic ketones can be obtained in high yield, and the present invention has been completed based on these facts.

（式中、Ｒ^１〜Ｒ^４は、それぞれ反応に関与しない１価の基を示す。環Ａは単環もしくは縮合多環の芳香環基または複素芳香環基を示し、その環を構成する原子には窒素原子、酸素原子もしくはイオウ原子を含んでいてもよく、また環が反応に関与しない基で置換されていてもよい。）で表されるカルボン酸を、一般式（II）
ＭＸｍ・Ｌｎ （ＩＩ）
（式中、Ｍはビスマス、ガリウム、インジウム、ハフニウム、希土類元素から選ばれる金属イオンを示す。Ｘはハロゲンアニオン、パーフルオロアルキルスルホナートアニオン、ビス（パーフルオロアルキルスルホニル）アミドアニオン、トリス（パーフルオロアルキルスルホニル）メチドアニオンから選ばれるアニオンを示す。Ｌは配位力のある中性分子を示す。ｍは金属Ｍの原子価数であり、ｎは０〜１０の整数である。）
で表されるルイス酸の触媒量と反応させることによる、一般式（III）

（式中、Ｒ^１〜Ｒ^４及び環Ａは、それぞれ前記と同じ意味を持つ。）で表される環状ケトン類を製造方法である。 That is, the present invention relates to the general formula (I)

(Wherein R ^{1 to} R ⁴ each represent a monovalent group not involved in the reaction. Ring A represents a monocyclic or condensed polycyclic aromatic ring group or heteroaromatic ring group, and atoms constituting the ring May contain a nitrogen atom, an oxygen atom, or a sulfur atom, and the ring may be substituted with a group that does not participate in the reaction.) A carboxylic acid represented by the general formula (II)
MXm · Ln (II)
(In the formula, M represents a metal ion selected from bismuth, gallium, indium, hafnium, and rare earth elements. X represents a halogen anion, a perfluoroalkylsulfonate anion, a bis (perfluoroalkylsulfonyl) amide anion, and tris (perfluoro). Alkylsulfonyl) represents an anion selected from methide anions, L represents a neutral molecule having a coordinating power, m is a valence number of metal M, and n is an integer of 0 to 10.)
By reacting with a catalytic amount of Lewis acid represented by the general formula (III)

(Wherein R ^{1 to} R ⁴ and ring A each have the same meaning as described above).

  According to the present invention, by using a small amount of a specific Lewis acid, the dehydration cyclization reaction of propionic acids having an aromatic ring proceeds rapidly, and various cyclic ketones, particularly indanones are easily obtained in high yield. In addition, since less Lewis acid is used, discharge of waste acid can be suppressed.

The carboxylic acid represented by the general formula (I) used as a raw material in the production method of the present invention has a propionic acid skeleton in which the 3-position is substituted with an aromatic ring group or a heteroaromatic ring group, and the substituent R ^{1 to} R ⁴ are not particularly limited as long as they do not adversely affect the cyclization reaction of the present invention.

R ^{1 to} R ⁴ in the general formula (I) are groups that do not participate in the cyclization reaction bonded to the alkylene chain of the propionic acid skeleton, and include, for example, a hydrogen atom, a halogen atom, methyl, ethyl, propyl, t- Examples include alkyl groups such as butyl, alkoxy groups such as methoxy and ethoxy, ester groups, and cyano groups.
In general formula (I), ring A is a monocyclic or condensed polycyclic aromatic ring group or heteroaromatic ring group, and atoms constituting those rings include one or more nitrogen atoms (N), An oxygen atom (O) or a sulfur atom (S) may be contained, and the ring may be substituted with a group not participating in the reaction. However, as shown in the general formula (I), these aromatic ring groups or heteroaromatic ring groups have a hydrogen atom bonded to at least one of the two atoms bonded to the carbon atom to which the propionic acid moiety is directly bonded. Must be a carbon atom.

  Specific examples of such aromatic ring group or heteroaromatic ring group A include, for example, phenyl group, 1-naphthyl group, 5,6,7,8-tetrahydro-2-naphthyl group, 2-anthryl group, 2- Phenanthryl group, 1-pyrenyl group, 3-thienyl group, 2-thianthryl group, 3-furyl group, 2-xanthenyl group, 3-pyrrolyl group, 3H-indol-2-yl group, 6-quinolyl group, 2-carbazolyl group Group and the like. Examples of groups that may be substituted on the aromatic ring group or heteroaromatic ring group A include halogen atoms, alkyl groups such as methyl, ethyl, propyl, and t-butyl, vinyl, 1-propenyl, and 1-butenyl. Alkenyl groups such as ethynyl and 1-propynyl, aryl groups such as phenyl, naphthyl and tolyl, alkoxy groups such as methoxy and ethoxy, aryloxy groups such as phenoxy, alkylthio groups such as methylthio, arylthio such as phenylthio Group, perfluoroalkyl group and the like.

Next, the Lewis acid used as a catalyst in the present invention has the following general formula (II):
MXm · Ln (II)
It is a metal compound represented by these.
In the general formula (II), M is a metal ion and is selected from rare earth elements such as bismuth, gallium, indium, hafnium, scandium, samarium, and ytterbium.
The anion X is preferably one whose conjugate acid exhibits high acidity, such as a halogen anion, a perfluoroalkylsulfonate anion, a bis (perfluoroalkylsulfonyl) amide anion, a tris (perfluoroalkylsulfonyl) methide anion, etc. Is mentioned.

  Further, the Lewis acid catalyst used in the dehydration cyclization reaction of the present invention may be coordinated with neutral molecules that do not adversely influence the reaction. This neutral molecule is L in the general formula (II), and examples thereof include ethers such as water and diethyl ether, and the number n is 0 to 10. The amount of the Lewis acid catalyst used for the reaction may be a small amount of so-called catalyst amount, and can be carried out in the range of 0.0001 to 50 mol% with respect to the compound (I). However, if the amount is too large, the economical efficiency of the reaction is deteriorated, so the range is preferably 0.01 to 30 mol%, more preferably 0.05 to 20 mol%.

Further, this reaction does not necessarily require a solvent, but a solvent may be used. Solvents that can be used include aromatic hydrocarbons, chlorinated hydrocarbons, nitrated hydrocarbons, and aliphatic hydrocarbons. Among them, aromatic hydrocarbons and halogenated hydrocarbons are used. Specific examples include toluene, chlorobenzene, 1,2-dichloroethane, 1,2-dichlorobenzene, α, α, α-trifluorotoluene and the like.
As the reaction temperature, the reaction does not proceed at an advantageous rate at a very low temperature, while a side reaction occurs at a too high temperature and the economic efficiency is poor. Therefore, the reaction temperature is generally selected from the range of 0 to 350 ° C., preferably Is carried out in the range of 60-280 ° C.

  Separation of the desired target product from the reaction product mixture is easily accomplished by using conventional separation and purification methods such as solvent extraction, recrystallization, distillation, chromatography, and sublimation.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.
Example 1

37.5 mg (0.25 mmol) of 3-phenylpropionic acid, 7.6 mg (mmol) of Tb (OSO ₂ CF ₃ ) ₃ and 20 μl of dodecane (internal standard for GC analysis) were mixed in 6 ml of chlorobenzene and sealed. The cyclization reaction was carried out by heating in an oil bath at 250 ° C. for 1.5 hours in the glass container. After completion of the reaction, it was confirmed by gas chromatography that 95% of 1-indanone was produced. Thereafter, the reaction mixture was purified using silica gel column chromatography to obtain 27 mg (82%) of 1-indanone.
Examples 2 to 21

  In the synthesis of 1-indanone by cyclization of 3-phenylpropionic acid in Example 1, the kind of Lewis acid catalyst used, the amount of catalyst, the amount of solvent, the reaction temperature and the reaction time were changed to those shown in Table 1, respectively. Except that, the cyclization reaction and the product were confirmed in the same manner as in Example 1. The results obtained in Examples 1 to 21 are shown in Table 1. The yields in the table are values determined by analysis by gas chromatography.

実施例２２〜３４

Examples 22-34

A cyclization reaction was carried out by heating 0.25 mmol of various 3-arylpropionic acids using Tb (OSO ₂ CF ₃ ) ₃ as a catalyst in an oil bath at 250 ° C. in 6 ml of chlorobenzene. Tables 2 and 3 show the raw material compounds used in the respective examples and the chemical structures, catalyst amounts, reaction times and product yields of the obtained products. In addition, although the yield in a table | surface is an isolated yield, the value which analyzed and determined by gas chromatography is shown in a parenthesis.

In the method of the present invention, various arylpropionic acids can be subjected to a dehydration cyclization reaction in one step to produce cyclic ketones in a high yield, and the reaction can be carried out only by using a small amount of Lewis acid catalyst. Since it is a good and simple production method that can reduce environmental pollution, it is a useful method for industrial implementation.

Claims (2)

Formula (I)

(Wherein R ^{1 to} R ⁴ each represent a monovalent group not involved in the reaction. Ring A represents a monocyclic or condensed polycyclic aromatic ring group or heteroaromatic ring group, and constitutes the ring. The atom may contain a nitrogen atom, an oxygen atom or a sulfur atom, and the ring may be further substituted with a group which does not participate in the reaction.) The carboxylic acid represented by the general formula (II)
MXm · Ln (II)
(In the formula, M represents a metal ion selected from bismuth, gallium, indium, hafnium, and rare earth elements. X represents a halogen anion, a perfluoroalkylsulfonate anion, a bis (perfluoroalkylsulfonyl) amide anion, and tris (perfluoro). Alkylsulfonyl) represents an anion selected from methide anions, L represents a neutral molecule having a coordinating power, m is a valence number of metal M, and n is an integer of 0 to 10.)
By reacting with a catalytic amount of Lewis acid represented by the general formula (III)

(Wherein R ^{1 to} R ⁴ and ring A each have the same meaning as described above). 2. The Lewis acid according to claim 1, wherein X in the general formula (II) is a Lewis acid which is an anion selected from a perfluoroalkylsulfonate anion, a bis (perfluoroalkylsulfonyl) amide anion, or a tris (perfluoroalkylsulfonyl) methide anion. Production method.