WO2010095604A1 - Alicyclic tetracarboxylic acid manufacturing method - Google Patents

Alicyclic tetracarboxylic acid manufacturing method Download PDF

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WO2010095604A1
WO2010095604A1 PCT/JP2010/052231 JP2010052231W WO2010095604A1 WO 2010095604 A1 WO2010095604 A1 WO 2010095604A1 JP 2010052231 W JP2010052231 W JP 2010052231W WO 2010095604 A1 WO2010095604 A1 WO 2010095604A1
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endo
formula
exo
tetracarboxylic acid
compound represented
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PCT/JP2010/052231
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French (fr)
Japanese (ja)
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秀雄 鈴木
浩 北
祐樹 高山
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日産化学工業株式会社
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Priority to CN201080017310.4A priority Critical patent/CN102395552B/en
Priority to JP2011500605A priority patent/JP5724870B2/en
Priority to KR1020117022004A priority patent/KR101700462B1/en
Publication of WO2010095604A1 publication Critical patent/WO2010095604A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C07C51/27—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with oxides of nitrogen or nitrogen-containing mineral acids
    • C07C51/275—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with oxides of nitrogen or nitrogen-containing mineral acids of hydrocarbyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C61/12—Saturated polycyclic compounds
    • C07C61/125—Saturated polycyclic compounds having a carboxyl group bound to a condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/22—All rings being cycloaliphatic the ring system containing eight carbon atoms, e.g. pentalene

Definitions

  • the present invention relates to bicyclo [3.3.0] octane-2-exo-4-exo-6-endo-8-endo-tetracarboxylic acid useful as a raw material for alicyclic polyimides used in the field of electronic materials and the like.
  • the present invention relates to a method for producing an alicyclic tetracarboxylic acid.
  • polyimide resins are widely used as electronic materials such as protective materials, insulating materials, and color filters in liquid crystal display elements and semiconductors because of their high mechanical strength, heat resistance, insulation, and solvent resistance. Yes.
  • an optical communication material such as an optical waveguide material is also expected.
  • the wholly aromatic polyimide resin is colored with a deep amber color, a problem arises in optical material applications that require high transparency. Further, since the wholly aromatic polyimide is insoluble in an organic solvent, it is actually necessary to obtain polyamic acid, which is a precursor thereof, by heat-dehydrating ring closure.
  • One method to achieve transparency is to obtain a polyimide precursor by polycondensation reaction between an alicyclic tetracarboxylic dianhydride and an aromatic diamine, and then imidize the precursor to produce a polyimide. It is known that a highly transparent polyimide can be obtained with less chromatic coloring (see Patent Documents 1 and 2).
  • Bicyclo [3.3.0] octane-2-exo-4-exo-6-endo-8-endo-tetracarboxylic acid-2: 4,6: 8-dianhydride represented by Polyimide using exo-4-exo-6-end-8-end-BODA) is excellent in printability and adhesion to the substrate, and does not peel off from the substrate during rubbing. It is known as a liquid crystal alignment treatment agent that can hardly damage the alignment film and can provide excellent voltage holding characteristics when driving a liquid crystal cell, and a liquid crystal alignment film using the same. (See Patent Document 3).
  • Exo-endo-tetracyclo [4.4.1 2,5 . 1 7,10 . 0 1,6 ] dodeca-3,8-diene (hereinafter abbreviated as exo-endo-TCDE) has the structural formula [4]
  • end-end-TCDE dodeca-3,8-diene
  • endo-endo-BOTC bicyclo [3.3.0] octane-2-endo-4-endo-6-endo-8-endo-tetracarboxylic acid
  • Non-Patent Document 2 an oxidation method using potassium permanganate is also known (see Non-Patent Document 2).
  • potassium ions are mixed into the target product, exo-endo-BOTC, and the next step is performed.
  • the dehydration ring-closing reaction with acetic anhydride it is mixed into the target product, exo-endo-BODA, and the structural formula [6]
  • JP-A-60-188427 JP 58-208322 A Japanese Patent Laid-Open No. 11-249148
  • the present invention relates to an exo-endo-BOTC which is a precursor of 2-exo-4-exo-6-endo-8-endo-BODA useful as a raw material for alicyclic polyimides used in the field of electronic materials and the like.
  • This is a method for producing alicyclic tetracarboxylic acid, which uses low-cost raw materials to obtain high-purity target products that do not contain impurities such as isomers and metals, and has a high reaction source concentration and volumetric efficiency. It is an object of the present invention to provide a production method having high productivity.
  • a compound represented by the following formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, and the compound represented by the following formula [B] is reacted by oxidizing the compound of the formula [A].
  • a method for producing an alicyclic tetracarboxylic acid characterized in that
  • the concentration of the aqueous solution of the oxidizing inorganic nitrogen oxide before addition of the compound represented by the formula [A] is 72 to 89% by mass, and the alicyclic tetracarboxylic acid according to (1) Production method, (3)
  • the compound represented by the formula [A] is converted into an exo-endo-tetracyclo [4.4.1 2,5 . 1 7,10 . 0 1,6 ] dodeca-3,8-diene and the compound represented by the formula [B] is a bicyclo [3.3.0] octane-2-exo-4-y represented by the formula [2].
  • Acid production method (7) The method for producing an alicyclic tetracarboxylic acid according to (6), wherein the organic solvent is a halogenated hydrocarbon, acetic acid, nitromethane, or a saturated hydrocarbon, (8) The method for producing an alicyclic tetracarboxylic acid according to (6) or (7), wherein the amount of the organic solvent present is 0.5 to 10 times by mass with respect to the compound represented by the formula [A]. . (9) The compound represented by the formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide at 0 to 50 ° C. The alicyclic tetracarboxylic acid according to any one of (1) to (8) Acid production method.
  • a process for producing an alicyclic tetracarboxylic acid (12) The method for producing an alicyclic tetracarboxylic acid according to (11), wherein the oxidizable inorganic nitrogen oxide to be added is 3 to 20 mol relative to 1 mol of the compound represented by the formula [A]. , (13) Further, the oxidizable inorganic nitrogen oxide to be added is at least one selected from the group consisting of nitric acid, nitrous acid, nitrogen dioxide, and nitrogen tetroxide. Production method of carboxylic acid. (14) The method for producing an alicyclic tetracarboxylic acid according to any one of (11) to (13), wherein an aqueous solution of an oxidizing inorganic nitrogen oxide to be further added is added at 20 to 60 ° C.
  • exo-endo- which is a precursor of 2-exo-4-exo-6-endo-8-endo-BODA, used as an alicyclic polyimide raw material useful in the field of electronic materials and the like.
  • inorganic nitrogen oxides which are inexpensive oxidants, alicyclic tetracarboxylic acids such as BOTC can be produced in high purity without impurities such as isomers of the target products and metals.
  • a production method with high raw material concentration and high volumetric efficiency is provided.
  • Cyclo [3.3.0] octane-tetracarboxylic acid which is a compound represented by the following formula [B] from 0 1,6 ] dodeca-3,8-diene (hereinafter also abbreviated as TCDE) (Hereinafter, also abbreviated as BOTC) is manufactured.
  • TCDE which is a raw material in the present invention can be produced by various methods.
  • TCDE can be produced by the following reaction scheme.
  • exo-endo-TCDE norbornadiene (ND) and cyclopentadiene (CP) (or dicyclopentadiene (DCPD)
  • ND norbornadiene
  • CP cyclopentadiene
  • DCPD dicyclopentadiene
  • exo-exo-TCDE a slight mixture
  • exo-endo-TCDE is preferred as the target product.
  • this exo-endo-TCDE has a boiling point close to that of endo-endo-TCDE, it is practically impossible to purify to high purity by mixing with endo-endo-TCDE even after re-distillation. Have difficulty.
  • the target product after the oxidation reaction can be easily purified as described later, and high-purity exo-endo-BOTC, etc.
  • a mixture of exo-endo-TCDE and endo-endo-TCDE can be used.
  • the mass ratio of exo-endo-TCDE / endo-endo-TCDE is preferably 60 to 99/40 to 1, particularly preferably 70 to 90/30 to 10.
  • the oxidizable inorganic nitrogen oxide is an inorganic oxide having an oxidizing power, preferably nitric acid (HNO 3 ), nitrous acid (HNO 2 ), nitrogen dioxide (NO 2 ), and nitrogen tetroxide (N 2 O). 4 ) and at least one selected from the group consisting of.
  • nitric acid is advantageous in terms of availability and operability.
  • an aqueous solution whose solvent is water is preferable.
  • the concentration of the inorganic nitrogen oxide in the aqueous solution of the oxidizing inorganic nitrogen oxide is preferably 70 to 89% by mass, particularly preferably 72 to 89% by mass, from the reaction rate and the selectivity of the target product.
  • concentration of the aqueous solution of inorganic nitrogen oxides is low, the purity of the target product in the obtained crystal is low, and purification is difficult, which is not preferable.
  • the amount of the inorganic nitrogen oxide used is preferably 5 to 40 moles per mole of the raw material TCDE, and more preferably 8 to 20 moles.
  • the reaction of TCDE When the oxidation reaction of TCDE is carried out with oxidizing inorganic nitrogen oxides, there is usually an induction period at the beginning of the reaction, and NOx gas is generated with a rapid exotherm after a while from the start of stirring. In this case, the reaction can be allowed to proceed gently by the presence of the catalyst.
  • the catalyst an aqueous nitric acid solution of nitrite, ammonium vanadate and / or vanadium (V) oxide can be preferably used.
  • a metal such as vanadium is mixed in the product, and its removal and purification is practically difficult.
  • the present inventors have found that the reaction can be started almost without the induction period and the reaction temperature can be controlled by using fuming nitric acid instead of using the above catalyst.
  • Fuming nitric acid also contributes to the oxidation of TCDE and is effectively consumed.
  • the fuming nitric acid a commercial product having a nitric acid concentration of preferably 90 to 99% by mass, particularly 90 to 98% by mass can be used.
  • the amount of fuming nitric acid is preferably 1 to 5 moles, and more preferably 2 to 3 moles per mole of TCDE of the raw material.
  • the oxidation reaction of TCDE in the present invention can proceed in the presence or absence of an organic solvent.
  • an organic solvent it is possible to control a large exotherm in the TCDE oxidation reaction, to alleviate a rapid temperature rise, and to obtain a purified target product with high purity of crystals. Since it becomes easy, it is preferable.
  • the use of an organic solvent is preferable because the outflow of generated NOx gas to the outside of the reaction system can be suppressed.
  • the amount of the organic solvent used is preferably 0.5 to 10 times by mass, particularly 1 to 5 times by mass with respect to the raw material TCDE because the reaction progresses slowly if the amount of the solvent is excessive.
  • the organic solvent is preferably a halogenated hydrocarbon having preferably 1 to 5 carbon atoms, a hydrocarbon having preferably 1 to 10 carbon atoms, acetic acid, nitromethane, dioxane, or the like.
  • halogenated hydrocarbons are particularly preferred because the purity of the target product in the crystals precipitated at the end of the oxidation reaction can be increased.
  • halogenated hydrocarbon examples include methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2-trichloroethane, 1-chloropropane, 2-chloropropane, 1,2-dichloropropane, 1, Examples include 3-dichloropropane, 2,2-dichloropropane, 1-chlorobutane, 2-chlorobutane, 1,4-dichlorobutane, and the like. Of these, 1,2-dichloroethane or 1,2-dichloropropane is preferable.
  • TCDE when TCDE is oxidized using an aqueous solution of oxidizing inorganic nitrogen oxide, a method of adding an aqueous solution of inorganic nitrogen oxide into a reaction vessel and adding raw material TCDE thereto (reverse addition method) ) is required.
  • reverse addition method it has been found that stable execution is possible while controlling the increase in reaction temperature, and the purity of the target product in the crystals obtained by precipitation at the end of the reaction is remarkably high.
  • the method of adding an aqueous solution of an oxidizing inorganic nitrogen oxide to the raw material TCDE (sequential addition method) is difficult to control the temperature by intense heat generation at any stage, as shown in a later comparative example.
  • the purity of the target product in the crystals obtained by the forward dropping method was found to be low and its purification was extremely difficult.
  • the raw material TCDE when the raw material TCDE is added to the aqueous solution of inorganic nitrogen oxide, for example, an oxidizing inorganic nitrogen oxide aqueous solution and fuming nitric acid are charged into the reaction vessel, and a small amount of raw material TCDE is added to the NOx gas. It was found that the exothermic reaction can be controlled more easily by dropping the remaining most of the raw material TCDE in sequence while adjusting the addition rate after the generation of the above. Further, the heat generation during the addition of the raw material TCDE can be easily controlled mildly by the presence of the organic solvent, but the organic solvent can be mixed with either the raw material TCDE or nitric acid or both.
  • the temperature in the oxidation reaction is divided into a temperature at the time of adding the raw material TCDE to the aqueous solution of the oxidizing inorganic nitrogen oxide, and a reaction temperature preferably with stirring after the addition of the TCDE.
  • the temperature at the time of addition of the former TCDE is preferably 0 to 50 ° C., and particularly preferably 20 to 40 ° C. from the viewpoint of the yield of the target product. It is preferable to carry out addition over time so that the added unreacted TCDE does not accumulate in the reaction vessel. If the temperature at the time of addition is too low, an induction period is observed, and unreacted TCDE accumulates in the reaction vessel and reacts with a sudden exotherm, which is not preferable. On the other hand, when it is too high, the generation of NOx gas is violently scattered to the outside of the reaction tank, and it is not preferable from the viewpoint of the yield of the target product.
  • the reaction temperature after the addition of the latter TCDE is preferably 10 to 69 ° C., particularly preferably 30 to 69 ° C. If the temperature is higher than the above, the yield of the target product is lowered, which is not preferable.
  • the yield of the target product is improved by maintaining the temperature after addition of TCDE in an aqueous solution of an oxidizing inorganic nitrogen oxide at a multistage temperature. That is, after the addition of TCDE, the yield of the desired product is improved by maintaining the temperature in two or more stages, preferably 30 to 59 ° C. in the first stage and preferably 60 to 100 ° C. in the second stage. In particular, it is preferable to hold at two or more stages of 40 to 55 ° C. in the first stage and 60 to 90 ° C. in the second stage.
  • the oxidation reaction time is preferably taken from the viewpoint of safety and in terms of the yield of the target product, combining the addition time of the raw material TCDE into the aqueous solution of the oxidizing inorganic nitrogen oxide and the subsequent reaction time. .
  • the addition time varies depending on the scale of the reaction and the cooling capacity of the reaction vessel, but is usually preferably 0.5 to 10 hours.
  • the reaction time after the addition is usually 5 to 120 hours, preferably 10 to 80 hours.
  • the reaction time for the first stage and the second stage is usually 5 to 50 hours, preferably 8 to 40 hours, more preferably 1 to 15 hours is preferred.
  • the added nitric acid is preferably 3 to 20 moles, more preferably 4 to 10 moles per mole of TCDE.
  • the concentration of nitric acid is preferably fuming nitric acid of 90 to 99% by mass.
  • the temperature at the time of addition of the above-described aqueous nitric acid solution is preferably 20 to 60 ° C., more preferably 30 to 50 ° C.
  • the yield of BOTC which is a target object can be raised by making temperature low.
  • the addition of the additional aqueous nitric acid solution is preferably performed 5 minutes to 2 hours, more preferably 10 minutes to 1 hour after the addition of TCDE to the aqueous nitric acid solution in order to allow the reaction to proceed slowly. Is preferred.
  • a higher yield can be obtained by gradually increasing the reaction temperature after the addition of an additional aqueous nitric acid solution.
  • the temperature of the reaction system is increased to preferably 50 to 90 ° C., more preferably 60 to 80 ° C. over 20 to 80 hours, more preferably 30 to 60 hours. Rate is obtained.
  • a method of raising the temperature a method of raising the temperature over multiple stages or a method of raising the temperature continuously may be used.
  • the present invention aims to produce BOTC.
  • exo-endo-BOTC which is a precursor of 2-exo-4-exo-6-endo-8-endo-BODA, is preferable.
  • exo-endo-BOTC when the target product is exo-endo-BOTC, such exo-endo-BOTC can be easily separated from by-produced endo-endo-BOTC, and high-purity exo-endo-BOTC can be easily obtained. Has features that can be manufactured.
  • the precipitated crystals are collected by filtration, washed with an organic solvent and dried to obtain a high-purity product of exo-endo-BOTC as a target product as primary crystals.
  • organic solvent used at this time for example, 1,2-dichloroethane (EDC), acetonitrile, ethyl acetate, ethyl acetate / n-heptane mixed solution, or the like can be used.
  • the concentrated solution obtained by concentrating the raw material TCDE to about 2 to 4 times by mass is left as it is, or cooled after adding an organic solvent.
  • the precipitated crystals are collected by filtration, washed with an organic solvent and dried to obtain exo-endo-BOTC as secondary crystals.
  • the organic solvent in this case, acetonitrile, ethyl acetate, ethyl acetate / n-heptane mixed solution, or the like can be used.
  • the primary and secondary crystals of the exo-endo-BOTC can be further purified by a known washing method or recrystallization method to increase the purity.
  • a washing method an organic solvent such as acetonitrile or ethyl acetate is added to the primary crystal or the secondary crystal and heated, ice-cooled, filtered, and dried.
  • water, N, N-dimethylformamide (DMF) or the like can be used as a solvent.
  • DMF N-dimethylformamide
  • the recovery rate can be increased in combination with ethyl acetate, acetonitrile or the like as a poor solvent.
  • 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE 88% / 22% under magnetic stirrer stirring.
  • 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE 88% / 22% under magnetic stirrer stirring.
  • the temperature was raised from 30 ° C. to 50 ° C. over 5 hours and 30 minutes, and then the first half was heated at 50 ° C. for 16 hours and further from 50 ° C. to 80 ° C. over 8 hours and 30 minutes, The latter half was stirred at 80 ° C. for 17 hours.
  • the first half was heated at 45 ° C. for 16 hours 30 minutes, and further from 45 ° C. to 70 ° C. over 8 hours 30 minutes, The latter half was stirred at 70 ° C. for 15 hours, and further stirred at 75 ° C. for 8 hours.
  • ozone generation amount 100 g / hr
  • the mixture was concentrated to 1.33 kPa (10 mmHg) at a bath temperature of 35 ° C. to obtain 1.61 kg of a viscous oil. Furthermore, 2 L of acetic acid was added and dissolved by stirring at a bath temperature of 35 ° C., then cooled with ice water and allowed to stand overnight.
  • this crystal had a target exo-endo-BOTC purity of 20%. That is, the forward dropping method has a low purity of the target product in the produced crystal and is difficult to purify.
  • the high purity 2-exo-4-exo-6-endo-8-endo-BOTC which is the alicyclic tetracarboxylic acid produced according to the present invention, is an alicyclic polyimide used in the field of electronic materials. It is useful as a raw material.
  • the entire contents of the specification, claims, and abstract of Japanese Patent Application No. 2009-039935 filed on Feb. 23, 2009 are incorporated herein as the disclosure of the specification of the present invention. Is.

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Abstract

Provided is a manufacturing method for alicyclic tetracarboxylic acids such as bicyclo [3.3.0) octane-2-exo-4-exo-6-endo-8-endo-tetracarboxylic acid of high purity and high producibility. The alicyclic tetracarboxylic acid manufacturing method is characterized in that a compound represented by formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, the formula [A] compound is oxidized, and a compound represented by formula [B] is produced. (1)

Description

脂環式テトラカルボン酸の製造方法Method for producing alicyclic tetracarboxylic acid
　本発明は、電子材料分野などで使用される脂環式ポリイミドの原料として有用なビシクロ［３．３．０］オクタン－２－エキソ－４－エキソ－６－エンド－８－エンド－テトラカルボン酸などの脂環式テトラカルボン酸の製造方法に関する。 The present invention relates to bicyclo [3.3.0] octane-2-exo-4-exo-6-endo-8-endo-tetracarboxylic acid useful as a raw material for alicyclic polyimides used in the field of electronic materials and the like. The present invention relates to a method for producing an alicyclic tetracarboxylic acid.
　一般に、ポリイミド樹脂はその特長である高い機械的強度、耐熱性、絶縁性、耐溶剤性のために、液晶表示素子や半導体における保護材料、絶縁材料、カラーフィルターなどの電子材料として広く用いられている。また、最近では光導波路用材料等の光通信用材料としての用途も期待されている。 In general, polyimide resins are widely used as electronic materials such as protective materials, insulating materials, and color filters in liquid crystal display elements and semiconductors because of their high mechanical strength, heat resistance, insulation, and solvent resistance. Yes. Recently, the use as an optical communication material such as an optical waveguide material is also expected.
　近年、この分野の発展は目覚ましく、それに対応して、用いられる材料に対しても益々高度な特性が要求される様になっている。即ち、単に耐熱性、耐溶剤性に優れるだけでなく、用途に応じた性能を多数合わせ有することが期待されている。 In recent years, the development of this field has been remarkable, and correspondingly, more and more advanced characteristics are required for the materials used. That is, it is expected not only to have excellent heat resistance and solvent resistance, but also to have a large number of performances depending on the application.
　しかし、特に、全芳香族ポリイミド樹脂においては、濃い琥珀色を呈し着色するため、高い透明性を要求される光学材料用途においては問題が生じてくる。また、全芳香族ポリイミドは有機溶剤に不溶であるため、実際にはその前駆体であるポリアミド酸を熱による脱水閉環によって得る必要がある。 However, in particular, since the wholly aromatic polyimide resin is colored with a deep amber color, a problem arises in optical material applications that require high transparency. Further, since the wholly aromatic polyimide is insoluble in an organic solvent, it is actually necessary to obtain polyamic acid, which is a precursor thereof, by heat-dehydrating ring closure.
　透明性を実現する一つの方法として、脂環式テトラカルボン酸二無水物と芳香族ジアミンとの重縮合反応によりポリイミド前駆体を得て、該当前駆体をイミド化してポリイミドを製造すれば、比較的着色が少なく、高透明性のポリイミドが得られることは知られている（特許文献１、２参照）。 One method to achieve transparency is to obtain a polyimide precursor by polycondensation reaction between an alicyclic tetracarboxylic dianhydride and an aromatic diamine, and then imidize the precursor to produce a polyimide. It is known that a highly transparent polyimide can be obtained with less chromatic coloring (see Patent Documents 1 and 2).
　近年、構造式［３］ In recent years, structural formula [3]
Figure JPOXMLDOC01-appb-C000003
 で表されるビシクロ［３．３．０］オクタン－２－エキソ－４－エキソ－６－エンド－８－エンド－テトラカルボン酸－２：４，６：８－二無水物（以下、２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡと略称する。）を使用するポリイミドが、基板への印刷性、密着性に優れ、かつラビング時に基板からの剥離がなく、またラビングによる配向膜への傷がつきにくく、液晶セル駆動時に優れた電圧保持特性が得られる液晶配向処理剤及びそれを用いた液晶配向膜として知られている。（特許文献３参照）。
Figure JPOXMLDOC01-appb-C000003
 Bicyclo [3.3.0] octane-2-exo-4-exo-6-endo-8-endo-tetracarboxylic acid-2: 4,6: 8-dianhydride represented by Polyimide using exo-4-exo-6-end-8-end-BODA) is excellent in printability and adhesion to the substrate, and does not peel off from the substrate during rubbing. It is known as a liquid crystal alignment treatment agent that can hardly damage the alignment film and can provide excellent voltage holding characteristics when driving a liquid crystal cell, and a liquid crystal alignment film using the same. (See Patent Document 3).
　しかしながら、２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡの前駆体である、構造式［２］ However, the structural formula [2], which is the precursor of 2-exo-4-exo-6-endo-8-endo-BODA
Figure JPOXMLDOC01-appb-C000004
 で表されるビシクロ［３．３.　０］オクタン－２－エキソ－４－エキソ－６－エンド－８－エンド－テトラカルボン酸（エキソ－エンド－ＢＯＴＣと略称する。）の製造法には、以下のような実用的な問題を抱えていた。
Figure JPOXMLDOC01-appb-C000004
 The production method of bicyclo [3.3.0] octane-2-exo-4-exo-6-endo-8-endo-tetracarboxylic acid (abbreviated as exo-endo-BOTC) represented by I had the following practical problems.
　即ち、エキソ－エンド－ＢＯＴＣの製造する反応では、原料である構造［１］ That is, in the reaction produced by exo-endo-BOTC, the raw material structure [1]
Figure JPOXMLDOC01-appb-C000005
 で表されるエキソ－エンド－テトラシクロ［４．４．１２，５．１７，１０．０１，６］ドデカ－３,８－ジエン（以下、エキソ－エンド－ＴＣＤＥと略称する。）中には、構造式［４］
Figure JPOXMLDOC01-appb-C000005
 Exo-endo-tetracyclo [4.4.1 2,5 . 1 7,10 . 0 1,6 ] dodeca-3,8-diene (hereinafter abbreviated as exo-endo-TCDE) has the structural formula [4]
Figure JPOXMLDOC01-appb-C000006
 で表されるエンド－エンド－テトラシクロ［４．４．１２，５．１７，１０．０１，６］ドデカ－３，８－ジエン（以下、エンド－エンド－ＴＣＤＥと略称する。）が、沸点が近接しているところから不純物としての混入が避けられず、これを分別することはたいへんなコスト増になる。このため、原料としては、上記不純物を含む混合物を使用するのが実用的である。
Figure JPOXMLDOC01-appb-C000006
 Endo-endo-tetracyclo [4.4.1 2,5 . 1 7,10 . 0 1,6 ] dodeca-3,8-diene (hereinafter abbreviated as “end-end-TCDE”) is inevitably mixed as an impurity since its boiling point is close, This is a significant cost increase. For this reason, it is practical to use a mixture containing the impurities as a raw material.
　一方、エキソ－エンド－ＴＣＤＥから目的生成物のエキソ－エンド－ＢＯＴＣの製造法として、従来、知られているオゾン酸化法（非特許文献１参照）では、目的生成物のエキソ－エンド－ＢＯＴＣ中には、原料中の不純物であるエンド－エンド－ＴＣＤＥから生成した構造式［５］ On the other hand, as a method for producing exo-endo-BOTC as a target product from exo-endo-TCDE, in the conventionally known ozone oxidation method (see Non-Patent Document 1), in the exo-endo-BOTC of the target product, Includes the structural formula [5] generated from endo-endo-TCDE, which is an impurity in the raw material.
Figure JPOXMLDOC01-appb-C000007
 で表されるビシクロ［３．３．０］オクタン－２－エンド－４－エンド－６－エンド－８－エンド－テトラカルボン酸（以下、エンド－エンド－ＢＯＴＣと略称する。）の混入が避けらず、高純度品を得るための精製操作に大きな問題を有する。また、オゾン酸化法の場合、反応中間体であるオゾニドは不安定な化合物であり、大量生産に際しての管理やオゾニドから蟻酸中での過酸化水素による分解反応時の激しい発熱に不安がある。更に、高価なオゾン発生装置や電力コスト等の経済性上の点でも工業的製法として相応しくない。
Figure JPOXMLDOC01-appb-C000007
 The mixture of bicyclo [3.3.0] octane-2-endo-4-endo-6-endo-8-endo-tetracarboxylic acid (hereinafter abbreviated as endo-endo-BOTC) represented by However, there is a big problem in the purification operation for obtaining a high-purity product. Further, in the case of the ozone oxidation method, the reaction intermediate ozonide is an unstable compound, and there is anxiety about management during mass production and intense heat generation during the decomposition reaction of ozonide with formic acid by hydrogen peroxide. Furthermore, it is not suitable as an industrial production method from the economical point of view such as expensive ozone generators and power costs.
　また、従来、過マンガン酸カリウムによる酸化法も知られているが（非特許文献２参照）、この方法の場合、カリウムイオンが目的生成物のエキソ－エンド－ＢＯＴＣ中に混入し、次工程の無水酢酸による脱水閉環反応において、目的生成物であるエキソ－エンド－ＢＯＤＡ中に混入するとともに、構造式［６］ Conventionally, an oxidation method using potassium permanganate is also known (see Non-Patent Document 2). In this method, potassium ions are mixed into the target product, exo-endo-BOTC, and the next step is performed. In the dehydration ring-closing reaction with acetic anhydride, it is mixed into the target product, exo-endo-BODA, and the structural formula [6]
Figure JPOXMLDOC01-appb-C000008
 で表されるビシクロ［３．３．０］オクタン－２－エンド－４－エンド－６－エンド－８－エンド－テトラカルボン酸－２：８，４：６－二無水物（以下、エンド－エンド－ＢＯＤＡと略称する。）への異性化副生を伴い、その精製に問題を残す。即ち、酸化反応後の目的生成物エキソ－エンド－ＢＯＴＣからのカリウムイオンの除去精製が問題である。
Figure JPOXMLDOC01-appb-C000008
 Bicyclo [3.3.0] octane-2-endo-4-endo-6-endo-8-endo-tetracarboxylic acid-2: 8, 4: 6 dianhydride (hereinafter referred to as endo- This is accompanied by isomerization by-product to abbreviated as Endo-BODA) and leaves problems in its purification. That is, the removal and purification of potassium ions from the target product exo-endo-BOTC after the oxidation reaction is a problem.
　更に、過マンガン酸カリウムによる酸化法の場合、高価な酸化剤を過剰量必要な上に、大量生産時には、反応後の残渣の廃棄処理法の問題が深刻になる。加えて、反応が基質濃度１質量％前後の希薄な水溶液で行う必要があり、容積効率が極めて低く採算性が甚だ悪い。また、目的生成物の単離には、反応後、膨大な溶媒の水を濃縮留去する必要がありエネルギ－負荷が大きい。過マンガン酸カリウムによる酸化法は、このようにいくつもの実用的に困難な課題を抱えている。 Furthermore, in the case of the oxidation method using potassium permanganate, an excessive amount of an expensive oxidant is required, and the problem of the disposal method of the residue after the reaction becomes serious during mass production. In addition, it is necessary to carry out the reaction with a dilute aqueous solution having a substrate concentration of about 1% by mass, and the volumetric efficiency is extremely low and the profitability is very bad. In addition, for isolation of the target product, it is necessary to concentrate and distill off an enormous amount of solvent water after the reaction, resulting in a large energy load. Thus, the oxidation method using potassium permanganate has a number of practically difficult problems.
特開昭６０－１８８４２７号公報JP-A-60-188427 特開昭５８－２０８３２２号公報JP 58-208322 A 特開平１１－２４９１４８号公報Japanese Patent Laid-Open No. 11-249148
　本発明は、電子材料分野などで使用される脂環式ポリイミドの原料として有用な２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡの前躯体であるエキソ－エンド－ＢＯＴＣなどの脂環式テトラカルボン酸の製造法であり、低廉な原料を用いて目的物の異性体や金属等の不純物を含まない高純度の目的物が得られ、かつ、反応の原料濃度が高く容積効率の高い生産性を有する製造法を提供することを課題とする。 The present invention relates to an exo-endo-BOTC which is a precursor of 2-exo-4-exo-6-endo-8-endo-BODA useful as a raw material for alicyclic polyimides used in the field of electronic materials and the like. This is a method for producing alicyclic tetracarboxylic acid, which uses low-cost raw materials to obtain high-purity target products that do not contain impurities such as isomers and metals, and has a high reaction source concentration and volumetric efficiency. It is an object of the present invention to provide a production method having high productivity.
　本発明者らは、上記課題を解決するため鋭意研究を行い、以下の要旨を有する本発明を完成させた。
（１）下記式［Ａ］で表される化合物を酸化性の無機窒素酸化物の水溶液に添加し、前記式［Ａ］の化合物を酸化反応させて下記式［Ｂ］で表される化合物を生成させることを特徴とする脂環式テトラカルボン酸の製造方法、 In order to solve the above-mentioned problems, the present inventors have intensively studied and completed the present invention having the following gist.
(1) A compound represented by the following formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, and the compound represented by the following formula [B] is reacted by oxidizing the compound of the formula [A]. A method for producing an alicyclic tetracarboxylic acid, characterized in that
Figure JPOXMLDOC01-appb-C000009
 （２）式［Ａ］で表される化合物が添加される前の酸化性の無機窒素酸化物の水溶液の濃度が７２～８９質量％である（１）に記載の脂環式テトラカルボン酸の製造方法、
（３）式［Ａ］で表される化合物が、式［１］で表されるエキソ－エンド－テトラシクロ［４．４．１２，５．１７，１０．０１，６］ドデカ－３,８－ジエンであり、式［Ｂ］で表される化合物が、式［２］で表されるビシクロ［３．３．０］オクタン－2－エキソ－4－エキソ－6－エンド－８－エンド－テトラカルボン酸である（１）又は（２）に記載の脂環式テトラカルボン酸の製造方法、
Figure JPOXMLDOC01-appb-C000009
 (2) The concentration of the aqueous solution of the oxidizing inorganic nitrogen oxide before addition of the compound represented by the formula [A] is 72 to 89% by mass, and the alicyclic tetracarboxylic acid according to (1) Production method,
(3) The compound represented by the formula [A] is converted into an exo-endo-tetracyclo [4.4.1 2,5 . 1 7,10 . 0 1,6 ] dodeca-3,8-diene and the compound represented by the formula [B] is a bicyclo [3.3.0] octane-2-exo-4-y represented by the formula [2]. The method for producing an alicyclic tetracarboxylic acid according to (1) or (2), which is exo-6-endo-8-endo-tetracarboxylic acid,
Figure JPOXMLDOC01-appb-C000010
 （４）酸化性の無機窒素酸化物が、硝酸、亜硝酸、二酸化窒素及び四酸化窒素からなる群から選ばれる少なくとも１種である（１）～（３）のいずれかに記載の脂環式テトラカルボン酸の製造方法、
（５）反応に使用する酸化性の無機窒素酸化物の合計量が、式［Ａ］で表される化合物の１モルに対して　５～４０モルである（１）～（４）のいずれかに記載の脂環式テトラカルボン酸の製造方法、
（６）式［Ａ］で表される化合物と酸化性の無機窒素酸化物とを、有機溶媒の存在下に酸化反応させる（１）～（５）のいずれかに記載の脂環式テトラカルボン酸の製造方法、
（７）有機溶媒がハロゲン化炭化水素、酢酸、ニトロメタン又は飽和炭化水素である（６）に記載の脂環式テトラカルボン酸の製造方法、
（８）有機溶媒の存在量が、式［Ａ］で表される化合物に対して０．５～１０質量倍である（６）又は（７）に記載の脂環式テトラカルボン酸の製造方法。
（９）式［Ａ］で表される化合物を、０～５０℃にて酸化性の無機窒素酸化物の水溶液に添加する（１）～（８）のいずれかに記載の脂環式テトラカルボン酸の製造方法。
（１０）式［Ａ］で表される化合物を酸化性の無機窒素酸化物の水溶液に添加した後、３０～５９℃にて保持し、次いで６０～１００℃にて保持する（１）～（８）のいずれかに記載の脂環式テトラカルボン酸の製造方法、
（１１）式［Ａ］で表される化合物を酸化性の無機窒素酸化物の水溶液に添加した後に、更に酸化性の無機窒素酸化物を添加する（１）～（１０）のいずれかに記載の脂環式テトラカルボン酸の製造方法、
（１２）更に加える酸化性の無機窒素酸化物が、式［Ａ］で表される化合物の１モルに対して３～２０モルである（１１）に記載の脂環式テトラカルボン酸の製造方法、
（１３）更に加える酸化性の無機窒素酸化物が、硝酸、亜硝酸、二酸化窒素及び四酸化窒素からなる群から選ばれる少なくとも１種である（１１）又は（１２）に記載の脂環式テトラカルボン酸の製造法。
（１４）更に添加する酸化性の無機窒素酸化物の水溶液を、２０～６０℃で添加する（１１）～（１３）のいずれかに記載の脂環式テトラカルボン酸の製造方法。
Figure JPOXMLDOC01-appb-C000010
 (4) The alicyclic group according to any one of (1) to (3), wherein the oxidizing inorganic nitrogen oxide is at least one selected from the group consisting of nitric acid, nitrous acid, nitrogen dioxide, and nitrogen tetroxide. Production method of tetracarboxylic acid,
(5) Any of (1) to (4), wherein the total amount of oxidizing inorganic nitrogen oxides used in the reaction is 5 to 40 mol with respect to 1 mol of the compound represented by the formula [A] A process for producing an alicyclic tetracarboxylic acid according to claim 1,
(6) The alicyclic tetracarboxylic acid according to any one of (1) to (5), wherein the compound represented by the formula [A] and an oxidizing inorganic nitrogen oxide are oxidized in the presence of an organic solvent. Acid production method,
(7) The method for producing an alicyclic tetracarboxylic acid according to (6), wherein the organic solvent is a halogenated hydrocarbon, acetic acid, nitromethane, or a saturated hydrocarbon,
(8) The method for producing an alicyclic tetracarboxylic acid according to (6) or (7), wherein the amount of the organic solvent present is 0.5 to 10 times by mass with respect to the compound represented by the formula [A]. .
(9) The compound represented by the formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide at 0 to 50 ° C. The alicyclic tetracarboxylic acid according to any one of (1) to (8) Acid production method.
(10) After adding the compound represented by the formula [A] to an aqueous solution of an oxidizing inorganic nitrogen oxide, hold at 30 to 59 ° C., and then hold at 60 to 100 ° C. (1) to ( 8) The method for producing an alicyclic tetracarboxylic acid according to any one of
(11) The compound represented by the formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, and then an oxidizing inorganic nitrogen oxide is further added. A process for producing an alicyclic tetracarboxylic acid,
(12) The method for producing an alicyclic tetracarboxylic acid according to (11), wherein the oxidizable inorganic nitrogen oxide to be added is 3 to 20 mol relative to 1 mol of the compound represented by the formula [A]. ,
(13) Further, the oxidizable inorganic nitrogen oxide to be added is at least one selected from the group consisting of nitric acid, nitrous acid, nitrogen dioxide, and nitrogen tetroxide. Production method of carboxylic acid.
(14) The method for producing an alicyclic tetracarboxylic acid according to any one of (11) to (13), wherein an aqueous solution of an oxidizing inorganic nitrogen oxide to be further added is added at 20 to 60 ° C.
　本発明によれば、電子材料分野等に有用な脂環式ポリイミド原料などとして使用される、２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡの前躯体であるエキソ－エンド－ＢＯＴＣなどの脂環式テトラカルボン酸が、低廉な酸化剤である無機窒素酸化物を用いることにより、目的物の異性体や金属等の不純物を含まない高純度にて製造でき、かつ、反応の原料濃度が高く容積効率の高い生産性のある製造法が提供される。 According to the present invention, exo-endo-, which is a precursor of 2-exo-4-exo-6-endo-8-endo-BODA, used as an alicyclic polyimide raw material useful in the field of electronic materials and the like. By using inorganic nitrogen oxides, which are inexpensive oxidants, alicyclic tetracarboxylic acids such as BOTC can be produced in high purity without impurities such as isomers of the target products and metals. A production method with high raw material concentration and high volumetric efficiency is provided.
　本発明では、下記式［Ａ］で表される化合物である、テトラシクロ［４．４．１２，５．１７，１０．０１，６］ドデカ－３，８－ジエン（（以下、ＴＣＤＥとも略称する。）から、下記式［Ｂ］で表される化合物である、シクロ［３．３．０］オクタン－テトラカルボン酸（以下、ＢＯＴＣとも略称する。）が製造される。 In the present invention, tetracyclo [4.4.1 2,5 ..., Which is a compound represented by the following formula [A]. 1 7,10 . Cyclo [3.3.0] octane-tetracarboxylic acid which is a compound represented by the following formula [B] from 0 1,6 ] dodeca-3,8-diene (hereinafter also abbreviated as TCDE) (Hereinafter, also abbreviated as BOTC) is manufactured.
Figure JPOXMLDOC01-appb-C000011
 　本発明における原料であるＴＣＤＥは、種々の方法で製造できるが、例えば、下記の反応スキームで製造することができる。
Figure JPOXMLDOC01-appb-C000011
 TCDE which is a raw material in the present invention can be produced by various methods. For example, TCDE can be produced by the following reaction scheme.
Figure JPOXMLDOC01-appb-C000012
 　即ち、ノルボルナジエン（ＮＤ）とシクロペンタジエン（ＣＰ）（又はジシクロペンタジエン（ＤＣＰＤ））を１７０～２３０℃の高温で加熱し、得られた反応粗物（エキソ－エンド－ＴＣＤＥ、エンド－エンド－ＴＣＤＥ及びエキソ－エキソ－ＴＣＤＥ（僅か）の混合物）を蒸留することにより目的物を単離できる。本発明では、エキソ－エンド－ＴＣＤＥが目的物として好ましい。しかしながら、このエキソ－エンド－ＴＣＤＥは、エンド－エンド－ＴＣＤＥと沸点が近接しているところから、再蒸留してもエンド－エンド－ＴＣＤＥが混入し、高純度まで精製することは実用的には困難である。
Figure JPOXMLDOC01-appb-C000012
 That is, norbornadiene (ND) and cyclopentadiene (CP) (or dicyclopentadiene (DCPD)) are heated at a high temperature of 170 to 230 ° C., and the resulting reaction crude product (exo-endo-TCDE, endo-endo-TCDE). And exo-exo-TCDE (a slight mixture) can be distilled to isolate the desired product. In the present invention, exo-endo-TCDE is preferred as the target product. However, since this exo-endo-TCDE has a boiling point close to that of endo-endo-TCDE, it is practically impossible to purify to high purity by mixing with endo-endo-TCDE even after re-distillation. Have difficulty.
　本発明では、エキソ－エンド－ＴＣＤＥとエンド－エンド－ＴＣＤＥとの混合物を使用しても、後記するように、酸化反応後の目的物が容易に精製でき、高純度のエキソ－エンド－ＢＯＴＣなどが製造できるので、本発明では、エキソ－エンド－ＴＣＤＥとエンド－エンド－ＴＣＤＥとの混合物が使用できる。この混合物としては、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥの質量割合が好ましくは６０～９９／４０～１、特に好ましくは７０～９０／３０～１０である。 In the present invention, even if a mixture of exo-endo-TCDE and endo-endo-TCDE is used, the target product after the oxidation reaction can be easily purified as described later, and high-purity exo-endo-BOTC, etc. In the present invention, a mixture of exo-endo-TCDE and endo-endo-TCDE can be used. In this mixture, the mass ratio of exo-endo-TCDE / endo-endo-TCDE is preferably 60 to 99/40 to 1, particularly preferably 70 to 90/30 to 10.
　次いで、本発明におけるＴＣＤＥの酸化反応について述べる。本発明では、酸化剤として、酸化性の無機窒素酸化物の水溶液を用いることが必要である。酸化性の無機窒素酸化物とは、酸化力がある無機酸化物であり、好ましくは、硝酸（ＨＮＯ３）、亜硝酸（ＨＮＯ２）、二酸化窒素（ＮＯ２）及び四酸化窒素（Ｎ２Ｏ４）からなる群から選ばれる少なくとも１種が挙げられる。なかでも、硝酸が入手性及び操作性上有利である。酸化性の無機窒素酸化物の水溶液としては、溶媒が水である水溶液が好ましい。酸化性の無機窒素酸化物の水溶液における無機窒素酸化物の濃度は、反応速度と目的物の選択性から好ましくは７０～８９質量％、特に好ましくは７２～８９質量％である。無機窒素酸化物の水溶液の濃度が低い場合は、得られた結晶中の目的物の純度が低くなり、精製が困難で好ましくない。無機窒素酸化物の使用量は、原料ＴＣＤＥ１モルに対して５～４０モル倍が好ましく、特には、８～２０モル倍が望ましい。 Next, the oxidation reaction of TCDE in the present invention will be described. In the present invention, it is necessary to use an aqueous solution of an oxidizing inorganic nitrogen oxide as the oxidizing agent. The oxidizable inorganic nitrogen oxide is an inorganic oxide having an oxidizing power, preferably nitric acid (HNO 3 ), nitrous acid (HNO 2 ), nitrogen dioxide (NO 2 ), and nitrogen tetroxide (N 2 O). 4 ) and at least one selected from the group consisting of. Of these, nitric acid is advantageous in terms of availability and operability. As the aqueous solution of the oxidizing inorganic nitrogen oxide, an aqueous solution whose solvent is water is preferable. The concentration of the inorganic nitrogen oxide in the aqueous solution of the oxidizing inorganic nitrogen oxide is preferably 70 to 89% by mass, particularly preferably 72 to 89% by mass, from the reaction rate and the selectivity of the target product. When the concentration of the aqueous solution of inorganic nitrogen oxides is low, the purity of the target product in the obtained crystal is low, and purification is difficult, which is not preferable. The amount of the inorganic nitrogen oxide used is preferably 5 to 40 moles per mole of the raw material TCDE, and more preferably 8 to 20 moles.
　酸化性の無機窒素酸化物によりＴＣＤＥの酸化反応を行う場合、通常、反応の初期には、誘導期があり、攪拌開始後しばらくしてから急激な発熱を伴ったＮＯｘガスの発生が起きる。この場合、触媒を存在させることにより反応を穏やかに進行させることができる。触媒としては、好ましくは、亜硝酸塩、バナジン酸アンモニウム及び／又は酸化バナジウム（Ｖ）の硝酸水溶液を使用できる。しかし、このような触媒を使用する場合には、生成物中にバナジウムなどの金属が混入し、その除去精製が実用的には困難である。 When the oxidation reaction of TCDE is carried out with oxidizing inorganic nitrogen oxides, there is usually an induction period at the beginning of the reaction, and NOx gas is generated with a rapid exotherm after a while from the start of stirring. In this case, the reaction can be allowed to proceed gently by the presence of the catalyst. As the catalyst, an aqueous nitric acid solution of nitrite, ammonium vanadate and / or vanadium (V) oxide can be preferably used. However, when such a catalyst is used, a metal such as vanadium is mixed in the product, and its removal and purification is practically difficult.
　本発明者らは、上記触媒を使用する代わりに、発煙硝酸を存在させることにより誘導期をほとんど無しに反応を開始することができ、反応温度の制御も可能になることを見出した。発煙硝酸は、ＴＣＤＥの酸化としても寄与し有効に消費される。発煙硝酸としては、硝酸濃度が好ましくは９０～９９質量％、特には９０～９８質量％の市販品を使用することができる。発煙硝酸の存在量は、原料のＴＣＤＥ１モルに対して１～５モル倍が好ましく、特に２～３モル倍が好ましい。 The present inventors have found that the reaction can be started almost without the induction period and the reaction temperature can be controlled by using fuming nitric acid instead of using the above catalyst. Fuming nitric acid also contributes to the oxidation of TCDE and is effectively consumed. As the fuming nitric acid, a commercial product having a nitric acid concentration of preferably 90 to 99% by mass, particularly 90 to 98% by mass can be used. The amount of fuming nitric acid is preferably 1 to 5 moles, and more preferably 2 to 3 moles per mole of TCDE of the raw material.
　本発明におけるＴＣＤＥの酸化反応は、有機溶媒の存在下又は非存在下で進行させることができる。特に、有機溶媒の存在下で進行させることにより、ＴＣＤＥの酸化反応における大きい発熱を制御し、急激な温度上昇を緩和することができ、また、得られる目的生成物の結晶の純度が高く精製が容易になるため好ましい。さらに、有機溶媒を使用することにより、発生するＮＯｘガスの反応系外への流出を抑制することもでき好ましい。有機溶媒の使用量は、溶媒量が多くなり過ぎると反応の進行が遅くなることから、原料ＴＣＤＥに対し０．５～１０質量倍、特には１～５質量倍が経済的にも好ましい。 The oxidation reaction of TCDE in the present invention can proceed in the presence or absence of an organic solvent. In particular, by proceeding in the presence of an organic solvent, it is possible to control a large exotherm in the TCDE oxidation reaction, to alleviate a rapid temperature rise, and to obtain a purified target product with high purity of crystals. Since it becomes easy, it is preferable. Furthermore, the use of an organic solvent is preferable because the outflow of generated NOx gas to the outside of the reaction system can be suppressed. The amount of the organic solvent used is preferably 0.5 to 10 times by mass, particularly 1 to 5 times by mass with respect to the raw material TCDE because the reaction progresses slowly if the amount of the solvent is excessive.
　上記有機溶媒としては、好ましくは、例えば、炭素数が好ましくは１～５のハロゲン化炭化水素、炭素数が好ましくは１～１０の炭化水素、酢酸、ニトロメタン、ジオキサン等が挙げられる。なかでも、ハロゲン化炭化水素は、酸化反応の終了時に析出する結晶中の目的物の純度が高くできるので特に好ましい。ハロゲン化炭化水素の具体例としては、塩化メチレン、クロロホルム、四塩化炭素、１，２－ジクロロエタン、１，１，２－トリクロロエタン、１－クロロプロパン、２－クロロプロパン、１，２－ジクロロプロパン、１，３－ジクロロプロパン、２，２－ジクロロプロパン、１－クロロブタン、２－クロロブタン、１，４－ジクロロブタン等が挙げられる。なかでも、１，２－ジクロロエタン、又は１，２－ジクロロプロパンが好ましい。 The organic solvent is preferably a halogenated hydrocarbon having preferably 1 to 5 carbon atoms, a hydrocarbon having preferably 1 to 10 carbon atoms, acetic acid, nitromethane, dioxane, or the like. Of these, halogenated hydrocarbons are particularly preferred because the purity of the target product in the crystals precipitated at the end of the oxidation reaction can be increased. Specific examples of the halogenated hydrocarbon include methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2-trichloroethane, 1-chloropropane, 2-chloropropane, 1,2-dichloropropane, 1, Examples include 3-dichloropropane, 2,2-dichloropropane, 1-chlorobutane, 2-chlorobutane, 1,4-dichlorobutane, and the like. Of these, 1,2-dichloroethane or 1,2-dichloropropane is preferable.
　本発明において、酸化性の無機窒素酸化物の水溶液を使用してＴＣＤＥを酸化する場合、反応槽中に無機窒素酸化物の水溶液を仕込み、これに対して原料ＴＣＤＥを添加する方法（逆添加法）を使用することが必要である。この逆添加法の場合、反応温度の上昇を制御しつつ安定した実施が可能になるとともに、反応終了時析出して得られる結晶中の目的物の純度が顕著に高いことが見出された。一方、原料ＴＣＤＥに対して酸化性の無機窒素酸化物の水溶液を添加する方法（順添加法）は、後の比較例に示されるように、いく段階での激しい発熱による温度制御が難しいとともに、順滴下法で得られる結晶中の目的物の純度が低く、その精製が極めて困難であることが判明した。 In the present invention, when TCDE is oxidized using an aqueous solution of oxidizing inorganic nitrogen oxide, a method of adding an aqueous solution of inorganic nitrogen oxide into a reaction vessel and adding raw material TCDE thereto (reverse addition method) ) Is required. In the case of this reverse addition method, it has been found that stable execution is possible while controlling the increase in reaction temperature, and the purity of the target product in the crystals obtained by precipitation at the end of the reaction is remarkably high. On the other hand, the method of adding an aqueous solution of an oxidizing inorganic nitrogen oxide to the raw material TCDE (sequential addition method) is difficult to control the temperature by intense heat generation at any stage, as shown in a later comparative example. The purity of the target product in the crystals obtained by the forward dropping method was found to be low and its purification was extremely difficult.
　本発明において、無機窒素酸化物の水溶液に対して、原料ＴＣＤＥを添加する場合、例えば、反応槽中に酸化性の無機窒素酸化物の水溶液と発煙硝酸を仕込み、原料ＴＣＤＥを少量添加しＮＯｘガスを発生させてから、残りの大半の原料ＴＣＤＥを添加速度を調節しながら順次滴下させることにより、一層、発熱反応の制御がしやすいことが判明した。また、原料ＴＣＤＥの添加時の発熱は、有機溶媒を存在させることにより温和に制御し易くなるが、有機溶媒を原料ＴＣＤＥと硝酸のどちらか又は両方に混合させて行うこともできる。 In the present invention, when the raw material TCDE is added to the aqueous solution of inorganic nitrogen oxide, for example, an oxidizing inorganic nitrogen oxide aqueous solution and fuming nitric acid are charged into the reaction vessel, and a small amount of raw material TCDE is added to the NOx gas. It was found that the exothermic reaction can be controlled more easily by dropping the remaining most of the raw material TCDE in sequence while adjusting the addition rate after the generation of the above. Further, the heat generation during the addition of the raw material TCDE can be easily controlled mildly by the presence of the organic solvent, but the organic solvent can be mixed with either the raw material TCDE or nitric acid or both.
　酸化反応における温度は、酸化性の無機窒素酸化物の水溶液に対する原料ＴＣＤＥの添加時の温度、及びＴＣＤＥの添加後の、好ましくは攪拌を伴う反応温度に分けられる。前者のＴＣＤＥの添加時の温度は、０～５０℃が好ましく、特には２０～４０℃で行うことが、目的物の収率面からも好ましい。添加した未反応のＴＣＤＥを反応槽内に蓄積させないように、添加時間をかけて行うことが好ましい。添加時の温度が低過ぎる場合は、誘導期が見られ、未反応のＴＣＤＥが反応槽内に蓄積され、後急激な発熱を伴なって反応するので好ましくない。また、高過ぎる場合にはＮＯｘガスの発生が激しく反応槽外へ飛散し、かつ目的物の収率面からも好ましくない。 The temperature in the oxidation reaction is divided into a temperature at the time of adding the raw material TCDE to the aqueous solution of the oxidizing inorganic nitrogen oxide, and a reaction temperature preferably with stirring after the addition of the TCDE. The temperature at the time of addition of the former TCDE is preferably 0 to 50 ° C., and particularly preferably 20 to 40 ° C. from the viewpoint of the yield of the target product. It is preferable to carry out addition over time so that the added unreacted TCDE does not accumulate in the reaction vessel. If the temperature at the time of addition is too low, an induction period is observed, and unreacted TCDE accumulates in the reaction vessel and reacts with a sudden exotherm, which is not preferable. On the other hand, when it is too high, the generation of NOx gas is violently scattered to the outside of the reaction tank, and it is not preferable from the viewpoint of the yield of the target product.
　一方、上記後者のＴＣＤＥの添加後の反応温度は好ましくは１０～６９℃、特に好ましくは３０～６９℃である。上記を超える高温にすると目的物の収量は低下するので好ましくはない。 On the other hand, the reaction temperature after the addition of the latter TCDE is preferably 10 to 69 ° C., particularly preferably 30 to 69 ° C. If the temperature is higher than the above, the yield of the target product is lowered, which is not preferable.
　本発明においては、酸化性の無機窒素酸化物の水溶液中へＴＣＤＥを添加後の温度を多段階の温度で保持することにより、目的物の収率を向上することが見出された。すなわち、ＴＣＤＥを添加後、１段目で好ましくは３０～５９℃、２段目で好ましくは６０～１００℃の２段階以上で保持することにより目的物の収率が向上する。特に、１段目で４０～５５℃、２段目で６０～９０℃の２段階以上で保持することが好ましい。 In the present invention, it has been found that the yield of the target product is improved by maintaining the temperature after addition of TCDE in an aqueous solution of an oxidizing inorganic nitrogen oxide at a multistage temperature. That is, after the addition of TCDE, the yield of the desired product is improved by maintaining the temperature in two or more stages, preferably 30 to 59 ° C. in the first stage and preferably 60 to 100 ° C. in the second stage. In particular, it is preferable to hold at two or more stages of 40 to 55 ° C. in the first stage and 60 to 90 ° C. in the second stage.
　酸化反応時間は、酸化性の無機窒素酸化物の水溶液中への原料ＴＣＤＥの添加時間とその後の反応時間とを合わせて、安全上及び目的物の収率面から時間をかけて行うのが好ましい。添加時間は、反応のスケールや反応槽の冷却能力により異なるが、通常は０．５～１０時間が好ましい。添加後の反応時間は、通常５～１２０時間、好ましくは１０～８０時間が好ましい。 The oxidation reaction time is preferably taken from the viewpoint of safety and in terms of the yield of the target product, combining the addition time of the raw material TCDE into the aqueous solution of the oxidizing inorganic nitrogen oxide and the subsequent reaction time. . The addition time varies depending on the scale of the reaction and the cooling capacity of the reaction vessel, but is usually preferably 0.5 to 10 hours. The reaction time after the addition is usually 5 to 120 hours, preferably 10 to 80 hours.
　上記したＴＣＤＥ添加後の反応温度を２段階以上に保持する場合には、１段目と２段目の反応時間は、いずれも、通常５～５０時間、好ましくは８～４０時間、さらに好ましくは１～１５時間であるのが好適である。
　本発明において、ＴＣＤＥを硝酸水溶液に添加した後に、更に硝酸水溶液を反応混合物溶液に添加するのが好ましい。この追加される硝酸は、ＴＣＤＥの１モルに対し３～２０モルであるのが好ましく、４～１０モルであるのがより好ましい。また、この硝酸の濃度は９０～９９質量％の発煙硝酸が好ましい。
　本発明では、上記追加される硝酸水溶液の添加時の温度は、２０～６０℃が好ましく、３０～５０℃がより好ましい。このように温度を低くすることにより目的物であるＢＯＴＣの収率を上げることができる。
　また、上記追加の硝酸水溶液の添加は、上記硝酸水溶液へのＴＣＤＥの添加後、好ましくは５分～２時間、より好ましくは１０分～１時間後に行うのが、反応を緩やかに進行させるために好適である。
　更に、追加の硝酸水溶液添加後に反応温度を徐々に上げていくことでより高い収率を得ることができる。具体的には、好ましくは２０～８０時間、より好ましくは３０～６０時間かけて、反応系の温度が好ましくは５０～９０℃まで、より好ましくは６０～８０℃まで上げていくことで高い収率が得られる。温度を上昇させる方法としては、多段階にわたって温度を上げていく方法でも、連続的に温度を上げていく方法でもよい。 When the reaction temperature after the above-mentioned TCDE addition is maintained in two or more stages, the reaction time for the first stage and the second stage is usually 5 to 50 hours, preferably 8 to 40 hours, more preferably 1 to 15 hours is preferred.
In the present invention, it is preferable to add an aqueous nitric acid solution to the reaction mixture solution after adding TCDE to the aqueous nitric acid solution. The added nitric acid is preferably 3 to 20 moles, more preferably 4 to 10 moles per mole of TCDE. The concentration of nitric acid is preferably fuming nitric acid of 90 to 99% by mass.
In the present invention, the temperature at the time of addition of the above-described aqueous nitric acid solution is preferably 20 to 60 ° C., more preferably 30 to 50 ° C. Thus, the yield of BOTC which is a target object can be raised by making temperature low.
Further, the addition of the additional aqueous nitric acid solution is preferably performed 5 minutes to 2 hours, more preferably 10 minutes to 1 hour after the addition of TCDE to the aqueous nitric acid solution in order to allow the reaction to proceed slowly. Is preferred.
Furthermore, a higher yield can be obtained by gradually increasing the reaction temperature after the addition of an additional aqueous nitric acid solution. Specifically, it is preferable that the temperature of the reaction system is increased to preferably 50 to 90 ° C., more preferably 60 to 80 ° C. over 20 to 80 hours, more preferably 30 to 60 hours. Rate is obtained. As a method of raising the temperature, a method of raising the temperature over multiple stages or a method of raising the temperature continuously may be used.
　本発明では、ＢＯＴＣの製造を目的とするが、なかでも、２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡの前躯体であるエキソ－エンド－ＢＯＴＣであるのが好ましい。本発明では、目的物がエキソ－エンド－ＢＯＴＣである場合、かかるエキソ－エンド－ＢＯＴＣは、副生するエンド－エンド－ＢＯＴＣとの分離が容易であり、高純度のエキソ－エンド－ＢＯＴＣが容易に製造できる特徴がある。 The present invention aims to produce BOTC. Among them, exo-endo-BOTC, which is a precursor of 2-exo-4-exo-6-endo-8-endo-BODA, is preferable. In the present invention, when the target product is exo-endo-BOTC, such exo-endo-BOTC can be easily separated from by-produced endo-endo-BOTC, and high-purity exo-endo-BOTC can be easily obtained. Has features that can be manufactured.
　すなわち、酸化反応終了後、析出した結晶を濾取後、有機溶媒で洗浄し乾燥することにより目的物であるエキソ－エンド－ＢＯＴＣの高純度品が一次結晶として得られる。このとき使用される有機溶媒としては、例えば、１，２－ジクロロエタン（ＥＤＣ）、アセトニトリル、酢酸エチル、酢酸エチル・ｎ－ヘプタン混合液等が使用できる。 That is, after completion of the oxidation reaction, the precipitated crystals are collected by filtration, washed with an organic solvent and dried to obtain a high-purity product of exo-endo-BOTC as a target product as primary crystals. As the organic solvent used at this time, for example, 1,2-dichloroethane (EDC), acetonitrile, ethyl acetate, ethyl acetate / n-heptane mixed solution, or the like can be used.
　更に、一次結晶を得る際の濾液と洗液を混合後、原料であるＴＣＤＥについて約２～４質量倍程度まで濃縮して得られた濃縮液をそのままか、又は有機溶媒を加えてから冷却し、析出した結晶を濾取後、有機溶媒で洗浄し乾燥することによりエキソ－エンド－ＢＯＴＣが二次結晶として得られる。この場合の有機溶媒としては、アセトニトリル、酢酸エチル、酢酸エチル・ｎ－ヘプタン混合液等が使用できる。 Further, after mixing the filtrate and the washing solution for obtaining the primary crystals, the concentrated solution obtained by concentrating the raw material TCDE to about 2 to 4 times by mass is left as it is, or cooled after adding an organic solvent. The precipitated crystals are collected by filtration, washed with an organic solvent and dried to obtain exo-endo-BOTC as secondary crystals. As the organic solvent in this case, acetonitrile, ethyl acetate, ethyl acetate / n-heptane mixed solution, or the like can be used.
　また、上記エキソ－エンド－ＢＯＴＣの一次結晶や二次結晶は、既知の洗浄方法や再結晶法によって更に精製して純度を上げることもできる。洗浄方法としては、一次結晶や二次結晶に対してアセトニトリルや酢酸エチルなどの有機溶媒を加えて加温し、氷冷し、濾過、乾燥することにより行われる。また、再結晶法は、溶媒として水やＮ，Ｎ－ジメチルホルムアミド（ＤＭＦ）等が使用できる。ＤＭＦを使用する場合は、貧溶媒として酢酸エチルやアセトニトリル等との組み合わせで回収率を上げることができる。 Further, the primary and secondary crystals of the exo-endo-BOTC can be further purified by a known washing method or recrystallization method to increase the purity. As a washing method, an organic solvent such as acetonitrile or ethyl acetate is added to the primary crystal or the secondary crystal and heated, ice-cooled, filtered, and dried. In the recrystallization method, water, N, N-dimethylformamide (DMF) or the like can be used as a solvent. When DMF is used, the recovery rate can be increased in combination with ethyl acetate, acetonitrile or the like as a poor solvent.
　以下に実施例を挙げ、本発明を具体的に説明するが、本発明の解釈はこれらに限定されるものではないことはもちろんである。
　尚、実施例で用いた分析法は以下の通りである。
　［１］　［質量分析（ＭＡＳＳ）］
　機種：ＬＸ－１０００（ＪＥＯＬ社製）、検出法：ＦＡＢ法．
　［２］　［１Ｈ ＮＭＲ］
　機種：Ｖａｒｉａｎ社製ＮＭＲ　Ｓｙｓｔｅｍ　４００ＮＢ（４００ＭＨｚ），
　測定溶媒：ＤＭＳＯ－ｄ６
標準物質：ｔｅｔｒａｍｅｔｈｙｌｓｉｌａｎｅ（ＴＭＳ）．
　［３］　［融点（ｍ．ｐ．）］
　機種：微量融点測定装置（ＭＰ－Ｓ３）（ヤナコ機器開発研究所社製） EXAMPLES The present invention will be specifically described below with reference to examples, but it is needless to say that the interpretation of the present invention is not limited to these examples.
The analytical methods used in the examples are as follows.
[1] [Mass Spectrometry (MASS)]
Model: LX-1000 (manufactured by JEOL), detection method: FAB method.
[2] [ 1 H NMR]
Model: Varian NMR System 400NB (400 MHz),
Measuring solvent: DMSO-d6
Standard substance: tetramethylsilane (TMS).
[3] [Melting point (mp)]
Model: Micro melting point measuring device (MP-S3) (manufactured by Yanaco Development Laboratory)
実施例１
　５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）９０．０ｇ（１ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）２８．０ｇ（０．４ｍｏｌ）及びＥＤＣ３１．６ｇを仕込み、マグネチックスターラー攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８３％／１７％の混合物３１．６ｇ（０．２ｍｏｌ）をＥＤＣ３１．６ｇに溶解した溶液を４５～５０℃で４５分かけて滴下した。続いて、５０～５５℃で１７時間攪拌した。 Example 1
In a 500 mL four-necked reaction flask, 90.0 g (1 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) 28 1.0 g (0.4 mol) and 31.6 g of EDC were charged, and 31.6 g (0.2 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 83% / 17% was stirred with a magnetic stirrer. The solution dissolved in 0.6 g was added dropwise at 45-50 ° C. over 45 minutes. Subsequently, the mixture was stirred at 50 to 55 ° C. for 17 hours.
　次いで、更に発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を滴下し、５５℃で２５時間攪拌すると白色結晶が析出した。続いて、氷冷してからろ過後、ＥＤＣで洗浄し、減圧乾燥すると一次白色結晶１６．０ｇ（純度９８％）（収率３３．０％）が得られた。 Next, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was further added dropwise and stirred at 55 ° C. for 25 hours to precipitate white crystals. Subsequently, after ice cooling, filtration, washing with EDC, and drying under reduced pressure, 16.0 g (purity 98%) of primary white crystals (yield 33.0%) were obtained.
　この結晶は、ＭＡＳＳ及び1H NMR分析結果より、エキソ－エンド－ＢＯＴＣであることを確認した。
　MASS ( ESI－, m/z(%) ) : 285([M-H]－, 100), 267(5)
1H NMR ( DMSO-d6, δppm ) : 12.15 ( s, 4H ),  3.17-3.07 ( m, 2H ), 2.78-2.66 ( m, 2H ),2.54-2.42 ( m, 2H ), 2.21 ( dt, J=12.0, 6.0 Hz, 1H ), 1.83-1.72 ( m, 2H ), 1.58 ( dt, J=12.0, 12.0 Hz, 1H ). This crystal was confirmed to be exo-endo-BOTC from MASS and 1 H NMR analysis results.
MASS (ESI -, m / z (%)): 285 ([MH] -, 100), 267 (5)
1 H NMR (DMSO-d 6 , δppm): 12.15 (s, 4H), 3.17-3.07 (m, 2H), 2.78-2.66 (m, 2H), 2.54-2.42 (m, 2H), 2.21 (dt, J = 12.0, 6.0 Hz, 1H), 1.83-1.72 (m, 2H), 1.58 (dt, J = 12.0, 12.0 Hz, 1H).
　更に、ろ液とＥＤＣ洗液を混合してから、重量が１０８ｇまで濃縮してからアセトニトリル２５ｇを加えた後、氷冷すると結晶が析出した。この結晶をろ過後、アセトニトリルで洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの二次結晶１．９ｇ（純度９０％）（収率４．０％）が得られた。
　尚、一次結晶及び二次結晶の金属分析では、Ｋ及びＭｎのいずれも検出限界以下（＜１ｐｐｍ）であった。
　なお、上記実施例における酸化反応は以下のとおりである。 Further, the filtrate and the EDC washing solution were mixed, and the weight was concentrated to 108 g, and then 25 g of acetonitrile was added, followed by cooling with ice to precipitate crystals. The crystals were filtered, washed with acetonitrile, and dried under reduced pressure to obtain 1.9 g (purity 90%) (yield 4.0%) of exo-endo-BOTC secondary crystals.
In the metal analysis of the primary and secondary crystals, both K and Mn were below the detection limit (<1 ppm).
In addition, the oxidation reaction in the said Example is as follows.
Figure JPOXMLDOC01-appb-C000013
Figure JPOXMLDOC01-appb-C000013
実施例２
　５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ４７．４ｇを仕込み、マグネチックスターラー攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％１５．８ｇ（０．１ｍｏｌ）の混合物をＥＤＣ１５．８ｇに溶解した溶液を３３～４０℃で１時間かけて滴下した。 Example 2
In a 500 mL four-neck reaction flask, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) ) 14.0 g (0.2 mol) and 47.4 g EDC were charged, and a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% 15.8 g (0.1 mol) under magnetic stirrer stirring. Was dissolved in 15.8 g of EDC dropwise at 33 to 40 ° C. over 1 hour.
　続いて、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を３０～３３℃で３５分かけて滴下した。４０℃で３時間攪拌後、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）３５．０ｇ（０．５ｍｏｌ）を３５℃で１０分かけて滴下した。その後、４０℃で４８時間攪拌した。
　続いて氷冷してから、ろ過し、ケーキをＥＤＣ３０ｍＬで２回洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶５．６ｇ（純度９８％）（収率２２．０％）が得られた。 Subsequently, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 30 to 33 ° C. over 35 minutes. After stirring at 40 ° C. for 3 hours, 35.0 g (0.5 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 35 ° C. over 10 minutes. Then, it stirred at 40 degreeC for 48 hours.
Subsequently, the mixture was cooled with ice, filtered, and the cake was washed twice with 30 mL of EDC and dried under reduced pressure to obtain 5.6 g (purity 98%) of primary pale yellow crystals (purity 98%) (yield 22.0%) of exo-endo-BOTC. Obtained.
実施例３
　５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ４７．４ｇを仕込み、マグネチックスターラー攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物を１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を４５～５５℃で１時間かけて滴下した。続いて、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４９．０ｇ（０．６ｍｏｌ）を４５～５０℃で３０分かけて滴下した。更に、５０～６５℃まで５時間かけて昇温し、後６５℃で１７時間攪拌した。
　続いて氷冷してから、ろ過し、ケーキをＥＤＣ３０ｍＬで２回洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶５．３ｇ（純度９８％）（収率２０．０％）が得られた。 Example 3
In a 500 mL four-neck reaction flask, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) ) 14.0 g (0.2 mol) and 47.4 g EDC were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% was stirred with a magnetic stirrer. ) In 15.8 g of EDC was added dropwise at 45 to 55 ° C. over 1 hour. Subsequently, 49.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 45 to 50 ° C. over 30 minutes. Further, the temperature was raised to 50 to 65 ° C. over 5 hours, followed by stirring at 65 ° C. for 17 hours.
Subsequently, the mixture was cooled on ice, filtered, and the cake was washed twice with 30 mL of EDC and dried under reduced pressure to obtain 5.3 g of exo-endo-BOTC primary pale yellow crystals (purity 98%) (yield 20.0%). Obtained.
実施例４
　５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ１５．８ｇを仕込み、マグネチックスターラー攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を３３～３８℃で１時間かけて滴下した。続いて、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を３２～４０℃で１０分かけて滴下した。続いて、４０℃～５０℃までを６時間かけて昇温してから、前半を５０℃で１６時間、更に５０℃～６５℃までを３時間かけて昇温してから、後半を６５℃で２０時間攪拌した。 Example 4
In a 500 mL four-neck reaction flask, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) ) 14.0 g (0.2 mol) and 15.8 g EDC were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% under magnetic stirrer stirring. Was dissolved in 15.8 g of EDC dropwise at 33-38 ° C. over 1 hour. Subsequently, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 32 to 40 ° C. over 10 minutes. Subsequently, the temperature was raised from 40 ° C. to 50 ° C. over 6 hours, the first half was heated at 50 ° C. for 16 hours, and the temperature was further raised from 50 ° C. to 65 ° C. over 3 hours. For 20 hours.
　続いて氷冷してからＥＤＣ３０ｍＬを添加し、攪拌後、ろ過し、ケーキをＥＤＣ３０ｍＬで２回洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶１０．２ｇ（純度９８％）（収率４０．０％）が得られた。 Then, after cooling with ice, 30 mL of EDC was added, stirred and filtered, and the cake was washed twice with 30 mL of EDC and dried under reduced pressure to give 10.2 g of exo-endo-BOTC primary pale yellow crystals (purity 98%) (yield) Rate 40.0%) was obtained.
　更に、ろ液とＥＤＣ洗液を混合してから、重量が３０ｇまで濃縮してからＥＤＣ３０ｍLを加えた後、氷冷すると結晶が析出した。この結晶をろ過後、ＥＤＣで洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの二次結晶１．２ｇ（純度９０％）（収率４．０％）が得られた。 Further, after the filtrate and EDC washing solution were mixed, the weight was concentrated to 30 g, and then 30 mL of EDC was added, followed by cooling with ice to precipitate crystals. The crystals were filtered, washed with EDC, and dried under reduced pressure to obtain 1.2 g of exo-endo-BOTC secondary crystals (purity 90%) (yield 4.0%).
　次に、前記一次結晶１０．２ｇにアセトニトリル４０ｇを加え８０℃で３０分攪拌した。続いて、氷冷してからろ過、酢酸エチル３０ｍＬで２回洗浄後減圧乾燥すると白色結晶８．６ｇが得られた。この結晶は1H NMR分析結果より、純度１００％のエキソ－エンド－ＢＯＴＣであることを確認した。
ｍ．ｐ．(℃)：２５５～２６０℃ Next, 40 g of acetonitrile was added to 10.2 g of the primary crystals, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, the mixture was cooled on ice, filtered, washed twice with 30 mL of ethyl acetate and dried under reduced pressure to obtain 8.6 g of white crystals. From the results of 1 H NMR analysis, this crystal was confirmed to be 100% pure exo-endo-BOTC.
m. p. (° C): 255-260 ° C
実施例５
　攪拌羽付き５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ１５．８ｇを仕込み、機械攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を３０～３７℃で１時間かけて滴下した。続いて，発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を３０～３３℃で２０分かけて滴下した。続いて、３３℃～５０℃までを５時間かけて昇温してから、前半を５０℃で１６時間、更に５０℃～６５℃までを９時間かけて昇温してから、後半を６５℃で２０時間攪拌した。 Example 5
In a 500 mL four-necked reaction flask with stirring blades, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1. 50 g / ml) 14.0 g (0.2 mol) and EDC 15.8 g were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% under mechanical stirring. ) In 15.8 g of EDC was added dropwise at 30 to 37 ° C. over 1 hour. Subsequently, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 30 to 33 ° C. over 20 minutes. Subsequently, the temperature was raised from 33 ° C. to 50 ° C. over 5 hours, the first half was heated at 50 ° C. for 16 hours, and the temperature was further raised from 50 ° C. to 65 ° C. over 9 hours. For 20 hours.
　続いて氷冷してからＥＤＣ３０ｍＬを添加し、攪拌後、ろ過し、ケーキをＥＤＣ２０ｍＬで２回洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣ一次淡黄色結晶１０．４ｇ（純度９８％）（収率４０．０％）が得られた。 Then, after cooling with ice, 30 mL of EDC was added, stirred and filtered, and the cake was washed twice with 20 mL of EDC and dried under reduced pressure to give 10.4 g of exo-endo-BOTC primary pale yellow crystals (purity 98%) (yield) 40.0%) was obtained.
　次に、前記一次結晶１０．０ｇに水２００ｇを加え１２０℃油浴で加温攪拌して溶解を確認してから、活性炭２ｇを加えて１２０℃で１時間３０分攪拌した。続いて、熱濾過して得られたろ液を８５ｇまで濃縮してから氷冷し、析出した結晶をろ過、減圧乾燥すると白色結晶７．５１ｇが得られた。この結晶は1H NMR分析結果より、純度１００％のエキソ－エンド－ＢＯＴＣであることを確認した。
ｍ．ｐ．(℃)：２５５～２６０℃ Next, after adding 200 g of water to 10.0 g of the primary crystals and heating and stirring in a 120 ° C. oil bath to confirm dissolution, 2 g of activated carbon was added and stirred at 120 ° C. for 1 hour and 30 minutes. Subsequently, the filtrate obtained by hot filtration was concentrated to 85 g and then ice-cooled. The precipitated crystals were filtered and dried under reduced pressure to obtain 7.51 g of white crystals. From the results of 1 H NMR analysis, this crystal was confirmed to be 100% pure exo-endo-BOTC.
m. p. (° C): 255-260 ° C
実施例６
　５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ１５．８ｇを仕込み、マグネチックスターラー攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を３０～４０℃で１時間かけて滴下した。３０～２５℃で２０分攪拌した後、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を３３～４０℃で５０分かけて滴下した。 Example 6
In a 500 mL four-neck reaction flask, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) ) 14.0 g (0.2 mol) and 15.8 g EDC were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% under magnetic stirrer stirring. Was dissolved in 15.8 g of EDC dropwise at 30 to 40 ° C. over 1 hour. After stirring at 30 to 25 ° C. for 20 minutes, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 33 to 40 ° C. over 50 minutes.
　続いて、４０℃～５０℃までを６時間かけて昇温してから、前半を５０℃で１６時間、更に５０℃～７０℃までを４時間かけて昇温してから、後半を７０℃で１７時間攪拌した。
　続いて氷冷してからろ過し、ケーキをＥＤＣ３０ｍＬで洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶１２．２ｇ（純度９０％）（収率４３．６％）が得られた。 Subsequently, the temperature was raised from 40 ° C. to 50 ° C. over 6 hours, the first half was heated at 50 ° C. for 16 hours, and the temperature was further raised from 50 ° C. to 70 ° C. over 4 hours. For 17 hours.
Subsequently, the mixture was cooled on ice and filtered, and the cake was washed with 30 mL of EDC and dried under reduced pressure to obtain 12.2 g (purity 90%) (43.6% yield) of primary pale yellow crystals of exo-endo-BOTC. .
　次に、前記一次結晶８．１ｇに水２２７ｇ（２８重量倍）を加え１１０℃油浴で加温攪拌して２０分後溶解を確認してから、内温９６℃で２０分攪拌した。続いて、熱濾過した後微少の残渣を水３２ｇ（４重量倍）で水洗し、ろ液と洗液の混合液を氷冷し、析出した結晶をろ過、減圧乾燥すると白色結晶５．８５ｇが得られた。この結晶は1H NMR分析結果より、純度１００％のエキソ－エンド－ＢＯＴＣであることを確認した。
ｍ．ｐ．(℃)：２6５～２６７℃ Next, 227 g (28 times by weight) of water was added to 8.1 g of the primary crystal, and the mixture was heated and stirred in a 110 ° C. oil bath for 20 minutes. After dissolution was confirmed, the mixture was stirred at an internal temperature of 96 ° C. for 20 minutes. Subsequently, after hot filtration, the minute residue was washed with 32 g (4 times by weight) of water, the mixture of the filtrate and the washings was ice-cooled, and the precipitated crystals were filtered and dried under reduced pressure to obtain 5.85 g of white crystals. Obtained. From the results of 1 H NMR analysis, this crystal was confirmed to be 100% pure exo-endo-BOTC.
m. p. (° C): 265-267 ° C
実施例７
　攪拌羽付き５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ１５．８ｇを仕込み、機械攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を３０～４０℃で１時間かけて滴下した。３０～２５℃で２０分攪拌した後、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を３３～４０℃で１時間かけて滴下した。 Example 7
In a 500 mL four-necked reaction flask with stirring blades, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1. 50 g / ml) 14.0 g (0.2 mol) and EDC 15.8 g were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% under mechanical stirring. ) In 15.8 g of EDC was added dropwise at 30 to 40 ° C. over 1 hour. After stirring at 30 to 25 ° C. for 20 minutes, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 33 to 40 ° C. over 1 hour.
　続いて、４０℃～５０℃までを６時間かけて昇温してから、前半を５０℃で１５時間、更に５０℃～７５℃までを７時間かけて昇温してから、後半を７５℃で２４時間攪拌した。
　続いて氷冷してから酢酸エチル／ｎ－ヘプタン＝１／１の３０ｍＬを加えてスラリー化してからろ過し、ケーキを酢酸エチル／ｎ－ヘプタン＝１／１の３０ｍＬを加えて洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶１２．０ｇ（純度９５％）（収率４５．３％）が得られた。 Subsequently, the temperature was raised from 40 ° C. to 50 ° C. over 6 hours, the first half was heated at 50 ° C. for 15 hours, and further the temperature was raised from 50 ° C. to 75 ° C. over 7 hours. For 24 hours.
Subsequently, after cooling with ice, 30 mL of ethyl acetate / n-heptane = 1/1 was added to form a slurry, followed by filtration, and the cake was washed with 30 mL of ethyl acetate / n-heptane = 1/1. When dried, 12.0 g (purity 95%) of primary pale yellow crystals of exo-endo-BOTC (yield 45.3%) were obtained.
実施例８
　攪拌羽付き５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ１５．８ｇを仕込み、機械攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を２５～３７℃で１時間２０分かけて滴下した。３０～２５℃で２０分攪拌した後、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を２７～３０℃で１時間かけて滴下した。 Example 8
In a 500 mL four-necked reaction flask with stirring blades, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1. 50 g / ml) 14.0 g (0.2 mol) and EDC 15.8 g were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% under mechanical stirring. ) In 15.8 g of EDC was added dropwise at 25 to 37 ° C. over 1 hour and 20 minutes. After stirring at 30 to 25 ° C. for 20 minutes, 42.0 g (0.6 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 27 to 30 ° C. over 1 hour.
　続いて、３０℃～５０℃までを５時間３０分かけて昇温してから、前半を５０℃で１６時間、更に５０℃～８０℃までを８時間３０分かけて昇温してから、後半を８０℃で１７時間攪拌した。 Subsequently, the temperature was raised from 30 ° C. to 50 ° C. over 5 hours and 30 minutes, and then the first half was heated at 50 ° C. for 16 hours and further from 50 ° C. to 80 ° C. over 8 hours and 30 minutes, The latter half was stirred at 80 ° C. for 17 hours.
　続いて氷冷してから酢酸エチル／ｎ－ヘプタン＝１／１の３０ｍＬを加えてスラリー化してからろ過し、ケーキを酢酸エチル／ｎ－ヘプタン＝１／１の３０ｍＬを加えて洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶１０．６ｇ（純度９５％）（収率４０．１％）が得られた。 Subsequently, after cooling with ice, 30 mL of ethyl acetate / n-heptane = 1/1 was added to form a slurry, followed by filtration, and the cake was washed with 30 mL of ethyl acetate / n-heptane = 1/1. Upon drying, 10.6 g (purity 95%) (yield 40.1%) of primary pale yellow crystals of exo-endo-BOTC were obtained.
実施例９
　攪拌羽付き５００ｍＬの四つ口反応フラスコに、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１８．０ｇ（０．２ｍｏｌ）、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４．０ｇ（０．２ｍｏｌ）及びＥＤＣ１５．８ｇを仕込み、機械攪拌下に、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）をＥＤＣ１５．８ｇに溶解した溶液を２５～３０℃で１時間３５分かけて滴下した。３０～２５℃で１５分攪拌した後、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）４２．０ｇ（０．６ｍｏｌ）を２５～３０℃で２５分かけて滴下した。 Example 9
In a 500 mL four-necked reaction flask with stirring blades, 18.0 g (0.2 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml), fuming nitric acid (concentration 90 to 94% by weight, density 1. 50 g / ml) 14.0 g (0.2 mol) and EDC 15.8 g were charged, and 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% under mechanical stirring. ) In 15.8 g of EDC was added dropwise at 25 to 30 ° C. over 1 hour and 35 minutes. After stirring at 30 to 25 ° C. for 15 minutes, fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) 42.0 g (0.6 mol) was added dropwise at 25 to 30 ° C. over 25 minutes.
　続いて、３０℃～４５℃までを６時間かけて昇温してから、前半を４５℃で１６時間３０分、更に４５℃～７０℃までを８時間３０分かけて昇温してから、後半を７０℃で１５時間攪拌した後、更に７５℃で８時間攪拌を続けた。 Subsequently, after raising the temperature from 30 ° C. to 45 ° C. over 6 hours, the first half was heated at 45 ° C. for 16 hours 30 minutes, and further from 45 ° C. to 70 ° C. over 8 hours 30 minutes, The latter half was stirred at 70 ° C. for 15 hours, and further stirred at 75 ° C. for 8 hours.
　続いて氷冷してから酢酸エチル／ｎ－ヘプタン＝１／１の３０ｍＬを加えてスラリー化してからろ過し、ケーキを酢酸エチル／ｎ－ヘプタン＝１／１の３０ｍＬを加えて洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣの一次淡黄色結晶１０．７ｇ（純度９５％）（収率４０．４％）が得られた。 Subsequently, after cooling with ice, 30 mL of ethyl acetate / n-heptane = 1/1 was added to form a slurry, followed by filtration, and the cake was washed with 30 mL of ethyl acetate / n-heptane = 1/1. When dried, 10.7 g (purity 95%) of primary pale yellow crystals of exo-endo-BOTC (yield 40.4%) were obtained.
比較例１（オゾン法）
　２０Ｌの反応槽にメタノール１０．４Ｌを仕込み、－４０℃に冷却した後、攪拌下にエキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８３％／２７％の混合物０．６２５ｋｇ（３．９５ｍｏｌ）を滴下した。続いて、オゾン発生機からオゾンを含む酸素ガス（オゾン発生量：１００ｇ／ｈｒ）を２５～３０ＮＬ／ｍｉｎ．の流速で５時間送入した。この間の液温は－２７～－３６℃（浴温：－４０～－５０℃）であった。その後窒素でバブリングした後、一夜静置した。 Comparative example 1 (ozone method)
10.4 L of methanol was charged into a 20 L reaction tank, cooled to −40 ° C., and then stirred under stirring, exo-endo-TCDE / endo-endo-TCDE = 83% / 27% mixture 0.625 kg (3.95 mol) Was dripped. Subsequently, oxygen gas containing ozone (ozone generation amount: 100 g / hr) was supplied from an ozone generator at 25 to 30 NL / min. At a flow rate of 5 hours. The liquid temperature during this period was −27 to −36 ° C. (bath temperature: −40 to −50 ° C.). Then, after bubbling with nitrogen, it was allowed to stand overnight.
　続いて、浴温３５℃で１.３３ｋＰａ（１０ｍｍＨｇ）まで濃縮し、粘性油状物１．６１ｋｇが得られた。更に、浴温３５℃で酢酸２Ｌを加えて攪拌溶解した後、氷水で冷却して一夜静置した。 Subsequently, the mixture was concentrated to 1.33 kPa (10 mmHg) at a bath temperature of 35 ° C. to obtain 1.61 kg of a viscous oil. Furthermore, 2 L of acetic acid was added and dissolved by stirring at a bath temperature of 35 ° C., then cooled with ice water and allowed to stand overnight.
　次に蟻酸２Ｌを５℃以下で滴下し、オゾニド／酢酸／蟻酸溶液を得た。
　１０Ｌ反応槽に３５％過酸化水素水０．７７Ｌ（８．９５ｍｏｌ）、酢酸０．４７Ｌ及び蟻酸０．４７Ｌを仕込み、５６℃に昇温したところに、オゾニド溶液０．４１Ｌを液温が６０℃以下に調節しながら注意深く滴下した。 Next, 2 L of formic acid was added dropwise at 5 ° C. or lower to obtain an ozonide / acetic acid / formic acid solution.
A 10 L reactor was charged with 0.77 L (8.95 mol) of 35% aqueous hydrogen peroxide, 0.47 L of acetic acid and 0.47 L of formic acid, and when the temperature was raised to 56 ° C., 0.41 L of the ozonide solution was heated to 60 ° C. The solution was carefully added dropwise while adjusting the temperature below ℃.
　滴下発熱終了後１．５時間経過してから、再びオゾニド溶液１．７３Ｌを液温が５２～６２℃で１．５時間かけて滴下した。続いて３５％過酸化水素水０．７７Ｌ（８．９５ｍｏｌ）を液温が５９～６１℃で０．５時間かけて滴下した。
　再びオゾニド溶液１．７３Ｌを液温が５９～６１℃で１時間かけて滴下した。続いて３５％過酸化水素水０．７７Ｌ（８．９５ｍｏｌ）を液温が５８～５９℃で滴下した。
　再びオゾニド溶液１．７３Ｌを液温が６１～６３℃で０．５時間かけて滴下した。発熱反応が終了するまで攪拌を３．５時間（液温６５℃以下に調整）続けた。その後４℃に冷却し、一夜静置した。 After 1.5 hours had elapsed from the end of the dropping heat generation, 1.73 L of the ozonide solution was again added dropwise at a liquid temperature of 52 to 62 ° C. over 1.5 hours. Subsequently, 0.77 L (8.95 mol) of 35% hydrogen peroxide was added dropwise at a liquid temperature of 59 to 61 ° C. over 0.5 hours.
Again, 1.73 L of ozonide solution was added dropwise over 1 hour at a liquid temperature of 59-61 ° C. Subsequently, 0.77 L (8.95 mol) of 35% hydrogen peroxide solution was added dropwise at a liquid temperature of 58 to 59 ° C.
Again, 1.73 L of ozonide solution was added dropwise over 0.5 hours at a liquid temperature of 61-63 ° C. Stirring was continued for 3.5 hours (adjusted to a liquid temperature of 65 ° C. or lower) until the exothermic reaction was completed. Thereafter, it was cooled to 4 ° C. and allowed to stand overnight.
　次に４℃～９０℃に５時間かけて昇温(７７℃付近で発熱あり)し、９２～９４℃で２時間攪拌した後、放冷（徐々に室温に戻し）一夜攪拌した。
　続いて、ろ過後１００ｍＬのアセトンで２回洗浄した後、減圧乾燥することにより白色結晶０．４８５ｋｇ（収率４２．０％）が得られた。この結晶の異性対比を分析の結果、目的とするエキソ－エンド－ＢＯＴＣ純度は８７％（収率３６％）で、不純物であるエンド－エンド－ＢＯＴＣは１３％（収率６％）含有していることが判明した。尚、ＫびＭｎの金属分析結果は、１ｐｐｍ以下であった。 Next, the temperature was raised to 4 ° C. to 90 ° C. over 5 hours (exothermic at around 77 ° C.), stirred at 92 to 94 ° C. for 2 hours, allowed to cool (slowly returned to room temperature) and stirred overnight.
Subsequently, after filtration, washing twice with 100 mL of acetone, and drying under reduced pressure, 0.485 kg of white crystals (yield 42.0%) was obtained. As a result of analysis of the isomer contrast of this crystal, the target exo-endo-BOTC purity was 87% (yield 36%), and the impurity endo-endo-BOTC contained 13% (yield 6%). Turned out to be. The metal analysis result of K and Mn was 1 ppm or less.
　続いて、この結晶を用いて、次の脱水工程を検討した結果、得られた結晶中の目的とする２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡ純度は８３％で、再結晶化を繰り返しても重合評価用純度までには到達できなかった。 Subsequently, as a result of examining the next dehydration step using this crystal, the target 2-exo-4-exo-6-endo-8-endo-BODA purity in the obtained crystal was 83%, Even when recrystallization was repeated, the purity for polymerization evaluation could not be reached.
比較例２（ＫＭｎＯ４法）
　攪拌羽付き２Ｌの四つ口反応フラスコに、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８３％／１７％の混合物１０ｇ（６３ｍｍｏｌ）と水１Ｌｇ仕込み、攪拌下に過マンガン酸カリウム（ＫＭｎＯ４)５３．８ｇ（３４０ｍｍｏｌ）（５．４モル倍）を２５℃～３４℃間で２時間かけて添加した。続いて２５℃で１８時間攪拌を続け反応を停止させた。その後ろ過により固形分を除いた後、ろ液を６０ｍＬまで濃縮した。続いて、冷却しながら３５%塩酸水３５ｇを注意深く滴下し酸性にしてから、一夜静置した。 Comparative Example 2 (KMnO 4 method)
A 2 L four-necked reaction flask with stirring blades was charged with 10 g (63 mmol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 83% / 17% and 1 Lg of water, and potassium permanganate (KMnO 4 ) was stirred. ) 53.8 g (340 mmol) (5.4 mole times) was added between 25 ° C. and 34 ° C. over 2 hours. Subsequently, stirring was continued at 25 ° C. for 18 hours to stop the reaction. Thereafter, the solid content was removed by filtration, and then the filtrate was concentrated to 60 mL. Subsequently, 35 g of 35% aqueous hydrochloric acid was carefully added dropwise with cooling to acidify, and then allowed to stand overnight.
　析出した結晶を水洗後、減圧乾燥することにより白色結晶６．８５ｇ（収率３８％）が得られた。この結晶の異性対比を分析の結果、目的とするエキソ－エンド－ＢＯＴＣ純度は９４％で、不純物であるエンド－エンド－ＢＯＴＣは６％含有していることが判明した。Ｋ及びＭｎの金属分析結果は、Ｋは０．１１％含有し、Ｍｎは１ｐｐｍ以下であった。 The precipitated crystals were washed with water and dried under reduced pressure to obtain 6.85 g (yield 38%) of white crystals. As a result of analysis of the isomer contrast of the crystal, it was found that the target exo-endo-BOTC purity was 94% and the impurity endo-endo-BOTC contained 6%. As a result of metal analysis of K and Mn, K contained 0.11%, and Mn was 1 ppm or less.
　次にここで得られたＢＯＴＣに１０モル倍の無水酢酸を加えて、１６０℃で４時間脱水反応させた後濃縮してから、１，４－ジオキサンで再結晶させて得率５４％で得られた結晶の分析結果は、２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＤＡ純度が９６％であったが、金属分析の結果は、Ｋは０．２８％含有して居り、次の重合反応に使用することができなかった。 Next, 10 mol-fold acetic anhydride was added to the BOTC obtained here, the mixture was dehydrated at 160 ° C. for 4 hours and concentrated, and then recrystallized from 1,4-dioxane to obtain a yield of 54%. The analysis result of the obtained crystal was that the purity of 2-exo-4-exo-6-endo-8-endo-BODA was 96%, but the result of metal analysis showed that K contained 0.28%. Could not be used for the next polymerization reaction.
比較例３ （順滴下法：ＥＤＣ溶媒）
　５００ｍＬ四つ口反応フラスコに、エキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）とＥＤＣ１５．８ｇを仕込んだ。これに対し２７℃で硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）４．５ｇ（０．０５ｍｏｌ）、続いて発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）３．５ｇ（０．０５ｍｏｌ）を滴下した。次に、４６℃で硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）１３．５ｇ（０．２５ｍｏｌ）を３０分かけて滴下した。 Comparative Example 3 (forward dropping method: EDC solvent)
A 500 mL four-necked reaction flask was charged with 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22% and 15.8 g of EDC. In contrast, at 27 ° C., nitric acid (concentration 69 to 70 wt%, density 1.42 g / ml) 4.5 g (0.05 mol), followed by fuming nitric acid (concentration 90 to 94 wt%, density 1.50 g / ml) 3.5 g (0.05 mol) was added dropwise. Next, 13.5 g (0.25 mol) of nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml) was added dropwise at 46 ° C. over 30 minutes.
　続いて５０～５５℃で発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）３８．５ｇ（０．５５ｍｏｌ）を３０分かけて滴下した。更に、５２℃で２３時間攪拌した。
　再び、発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）１４ｇ（０．２ｍｏｌ）を５２℃で５分かけて滴下してから、５２℃で３２時間攪拌した。 Subsequently, 38.5 g (0.55 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 50 to 55 ° C. over 30 minutes. Furthermore, it stirred at 52 degreeC for 23 hours.
Again, 14 g (0.2 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was added dropwise at 52 ° C. over 5 minutes, and then stirred at 52 ° C. for 32 hours.
　続いて氷冷してからＥＤＣ３０ｍｌを添加し、攪拌後、ろ過し、ケーキをＥＤＣ３０ｍｌで２回洗浄し、減圧乾燥するとエキソ－エンド－ＢＯＴＣ一次白色結晶５．３ｇが得られた。この結晶は1H NMR分析結果より、目的とするエキソ－エンド－ＢＯＴＣ純度は４０％であった。 Subsequently, after cooling with ice, 30 ml of EDC was added, stirred, and filtered. The cake was washed twice with 30 ml of EDC and dried under reduced pressure to obtain 5.3 g of exo-endo-BOTC primary white crystals. From the results of 1 H NMR analysis, this crystal had a target exo-endo-BOTC purity of 40%.
比較例４ （順滴下法：無溶媒）
　５００ｍＬの四つ口反応フラスコにエキソ－エンド－ＴＣＤＥ／エンド－エンド－ＴＣＤＥ＝８８％／２２％の混合物１５．８ｇ（０．１ｍｏｌ）を仕込んだ。これに対し、４０℃で硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）３６ｇ（０．４ｍｏｌ）を３０分かけて滴下した後、続いて発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）７ｇ（０．１ｍｏｌ）を滴下した。次に、４０℃で発煙硝酸（濃度９０～９４重量％、密度１．５０ｇ／ｍｌ）７ｇ（０．１ｍｏｌ）を１０分で滴下し、更に、硝酸（濃度６９～７０重量％、密度１．４２ｇ／ｍｌ）３６ｇ（０．４ｍｏｌ）を１０分かけて滴下した。続いて５０℃で２２時間攪拌した。更に、５２～５７℃で２４時間攪拌した。 Comparative example 4 (forward dripping method: no solvent)
A 500 mL four-necked reaction flask was charged with 15.8 g (0.1 mol) of a mixture of exo-endo-TCDE / endo-endo-TCDE = 88% / 22%. In contrast, nitric acid (concentration 69 to 70% by weight, density 1.42 g / ml) 36 g (0.4 mol) was added dropwise at 40 ° C. over 30 minutes, followed by fuming nitric acid (concentration 90 to 94% by weight, 7 g (0.1 mol) of 1.50 g / ml density was added dropwise. Next, at 40 ° C., 7 g (0.1 mol) of fuming nitric acid (concentration 90 to 94% by weight, density 1.50 g / ml) was dropped in 10 minutes, and nitric acid (concentration 69 to 70% by weight, density 1. 42 g / ml) and 36 g (0.4 mol) were added dropwise over 10 minutes. Subsequently, the mixture was stirred at 50 ° C. for 22 hours. Further, the mixture was stirred at 52 to 57 ° C. for 24 hours.
　続いて氷冷してからＥＤＣ３０ｍｌを添加し、攪拌後、ろ過し、ケーキをＥＤＣ３０ｍｌで２回洗浄し、減圧乾燥すると白色結晶１４．５ｇが得られた。この結晶は1H NMR分析結果より、目的とするエキソ－エンド－ＢＯＴＣ純度は２０％であった。即ち、順滴下法は、生成結晶中の目的物純度が低く、精製が困難であった。 Then, after cooling with ice, 30 ml of EDC was added, and after stirring, it was filtered. The cake was washed twice with 30 ml of EDC and dried under reduced pressure to obtain 14.5 g of white crystals. From the result of 1 H NMR analysis, this crystal had a target exo-endo-BOTC purity of 20%. That is, the forward dropping method has a low purity of the target product in the produced crystal and is difficult to purify.
参考例１：ＢＯＤＡ合成
　１００ｍｌの四つ口反応フラスコに実施例５で得られたＢＯＴＣ一次晶を水から再結晶した白色結晶５．２ｇ（１８．１ｍｍｏｌ）と無水酢酸３７．０ｇを仕込み、マグネチックスターラー攪拌下に、昇温し１２０℃油浴で２０分反応させると、スラリー液は均一透明液になった。更に１０分間攪拌を続けた後反応を停止した後、重量１６ｇまで濃縮してからスラリー液を氷冷した。この結晶をろ過した後、トルエンで２回洗浄してから、減圧乾燥すると白色結晶４．２ｇ（１６．８ｍｍｏｌ）（収率９２．８％）が得られた。 Reference Example 1: Synthesis of BODA A 100 ml four-necked reaction flask was charged with 5.2 g (18.1 mmol) of white crystals obtained by recrystallizing the BOTC primary crystal obtained in Example 5 from water and 37.0 g of acetic anhydride, When the temperature was raised and the reaction was carried out in a 120 ° C. oil bath for 20 minutes while stirring with a tic stirrer, the slurry became a uniform transparent liquid. After further stirring for 10 minutes, the reaction was stopped, and then concentrated to a weight of 16 g, and the slurry was ice-cooled. The crystals were filtered, washed twice with toluene, and then dried under reduced pressure to obtain 4.2 g (16.8 mmol) of white crystals (yield 92.8%).
　この結晶は、ＭＡＳＳ及び1H NMR分析結果より、2－エキソ－4－エキソ－6－エンド－８－エンド－ＢＯＤＡであることを確認した。ｍｐ．２３１～２３３℃
　尚、この結晶の金属分析の結果、Ｋは、１ｐｐｍ以下であった。 This crystal was confirmed to be 2-exo-4-exo-6-endo-8-endo-BODA from MASS and 1 H NMR analysis results. mp. 231 to 233 ° C
As a result of metal analysis of this crystal, K was 1 ppm or less.
Figure JPOXMLDOC01-appb-C000014
Figure JPOXMLDOC01-appb-C000014
　本発明の製造される脂環式テトラカルボン酸である、高純度の２－エキソ－４－エキソ－６－エンド－８－エンド－ＢＯＴＣなどは、電子材料分野などで使用される脂環式ポリイミドの原料などして有用である。

　なお、２００９年２月２３日に出願された日本特許出願２００９－０３９９３５号の明細書、特許請求の範囲、及び要約書の全内容をここに引用し、本発明の明細書の開示として、取り入れるものである。 The high purity 2-exo-4-exo-6-endo-8-endo-BOTC, which is the alicyclic tetracarboxylic acid produced according to the present invention, is an alicyclic polyimide used in the field of electronic materials. It is useful as a raw material.

The entire contents of the specification, claims, and abstract of Japanese Patent Application No. 2009-039935 filed on Feb. 23, 2009 are incorporated herein as the disclosure of the specification of the present invention. Is.

Claims (14)

  1. 　下記式［Ａ］で表される化合物を酸化性の無機窒素酸化物の水溶液に添加し、前記式［Ａ］で表される化合物を酸化反応させて下記式［Ｂ］で表される化合物を生成させることを特徴とする脂環式テトラカルボン酸の製造方法。
    Figure JPOXMLDOC01-appb-C000001
         A compound represented by the following formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, and the compound represented by the formula [A] is subjected to an oxidation reaction to obtain a compound represented by the following formula [B]. A method for producing an alicyclic tetracarboxylic acid, characterized by comprising:
    Figure JPOXMLDOC01-appb-C000001
  2. 　式［Ａ］で表される化合物が添加される前の酸化性の無機窒素酸化物の水溶液の濃度は７２～８９質量％である請求項１に記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to claim 1, wherein the concentration of the aqueous solution of the oxidizing inorganic nitrogen oxide before the compound represented by the formula [A] is added is 72 to 89% by mass.
  3. 　式［Ａ］で表される化合物が、式［１］で表されるエキソ－エンド－テトラシクロ［４．４．１２，５．１７，１０．０１，６］ドデカ－３,８－ジエンであり、式［Ｂ］で表される化合物が式［２］で表されるビシクロ［３．３．０］オクタン－2－エキソ－4－エキソ－6－エンド－８－エンド－テトラカルボン酸である請求項１又は２に記載の脂環式テトラカルボン酸の製造方法。
    Figure JPOXMLDOC01-appb-C000002
         The compound represented by the formula [A] is an exo-endo-tetracyclo [4.4.1 2,5 . 1 7,10 . Bicyclo [3.3.0] octane-2-exo-4-exo, which is 0 1,6 ] dodeca-3,8-diene and the compound represented by the formula [B] is represented by the formula [2] The process for producing an alicyclic tetracarboxylic acid according to claim 1 or 2, which is -6-endo-8-endo-tetracarboxylic acid.
    Figure JPOXMLDOC01-appb-C000002
  4. 　酸化性の無機窒素酸化物が、硝酸、亜硝酸、二酸化窒素及び四酸化窒素からなる群から選ばれる少なくとも１種である請求項１～３のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The alicyclic tetracarboxylic acid production according to any one of claims 1 to 3, wherein the oxidizable inorganic nitrogen oxide is at least one selected from the group consisting of nitric acid, nitrous acid, nitrogen dioxide and nitric oxide. Method.
  5. 　反応に使用する酸化性の無機窒素酸化物の合計量が、式［Ａ］で表される化合物の１モルに対して５～４０モルである請求項１～４のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The alicyclic ring according to any one of claims 1 to 4, wherein the total amount of oxidizing inorganic nitrogen oxides used in the reaction is 5 to 40 mol with respect to 1 mol of the compound represented by the formula [A]. A method for producing a tetracarboxylic acid of formula.
  6. 　式［Ａ］で表される化合物と酸化性の無機窒素酸化物とを、有機溶媒の存在下に酸化反応させる請求項１～５のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to any one of claims 1 to 5, wherein the compound represented by the formula [A] and an oxidizing inorganic nitrogen oxide are oxidized in the presence of an organic solvent.
  7. 　有機溶媒がハロゲン化炭化水素、酢酸、ニトロメタン又は飽和炭化水素である請求項６に記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to claim 6, wherein the organic solvent is a halogenated hydrocarbon, acetic acid, nitromethane, or a saturated hydrocarbon.
  8. 　有機溶媒の存在量が、式［Ａ］で表される化合物に対して０．５～１０質量倍である請求項６又は７に記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to claim 6 or 7, wherein the abundance of the organic solvent is 0.5 to 10 times the mass of the compound represented by the formula [A].
  9. 　式［Ａ］で表される化合物を、０～５０℃にて酸化性の無機窒素酸化物の水溶液に添加する請求項１～８のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to any one of claims 1 to 8, wherein the compound represented by the formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide at 0 to 50 ° C.
  10. 　式［Ａ］で表される化合物を酸化性の無機窒素酸化物の水溶液に添加した後、３０～５９℃にて保持し、次いで６０～１００℃にて保持する請求項１～９のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The compound represented by the formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, maintained at 30 to 59 ° C, and then maintained at 60 to 100 ° C. The manufacturing method of alicyclic tetracarboxylic acid as described in any one of.
  11. 　式［Ａ］で表される化合物を酸化性の無機窒素酸化物の水溶液に添加した後に、更に酸化性の無機窒素酸化物を添加する請求項１～１０のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The alicyclic tetragonal compound according to any one of claims 1 to 10, wherein the compound represented by the formula [A] is added to an aqueous solution of an oxidizing inorganic nitrogen oxide, and then an oxidizing inorganic nitrogen oxide is further added. A method for producing carboxylic acid.
  12. 　更に添加する酸化性の無機窒素酸化物が、式［Ａ］で表される化合物の１モルに対して３～２０モルである請求項１１に記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to claim 11, wherein the oxidizable inorganic nitrogen oxide to be added is 3 to 20 mol per 1 mol of the compound represented by the formula [A].
  13. 　更に添加する酸化性の無機窒素酸化物が、硝酸、亜硝酸、二酸化窒素及び四酸化窒素からなる群から選ばれる少なくとも１種である請求項１１又は１２に記載の脂環式テトラカルボン酸の製造方法。 Furthermore, the oxidizing inorganic nitrogen oxide to add is at least 1 sort (s) chosen from the group which consists of nitric acid, nitrous acid, nitrogen dioxide, and nitric oxide, The manufacture of the alicyclic tetracarboxylic acid of Claim 11 or 12 Method.
  14. 　更に添加する酸化性の無機窒素酸化物の水溶液を、２０～６０℃で添加する請求項１１～１３のいずれかに記載の脂環式テトラカルボン酸の製造方法。 The method for producing an alicyclic tetracarboxylic acid according to any one of claims 11 to 13, wherein an aqueous solution of an oxidizing inorganic nitrogen oxide to be further added is added at 20 to 60 ° C.
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