JP4995633B2 - 2-Adamantanone production method - Google Patents
2-Adamantanone production method Download PDFInfo
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- JP4995633B2 JP4995633B2 JP2007128465A JP2007128465A JP4995633B2 JP 4995633 B2 JP4995633 B2 JP 4995633B2 JP 2007128465 A JP2007128465 A JP 2007128465A JP 2007128465 A JP2007128465 A JP 2007128465A JP 4995633 B2 JP4995633 B2 JP 4995633B2
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- IYKFYARMMIESOX-UHFFFAOYSA-N adamantanone Chemical compound C1C(C2)CC3CC1C(=O)C2C3 IYKFYARMMIESOX-UHFFFAOYSA-N 0.000 title claims description 30
- 238000004519 manufacturing process Methods 0.000 title claims description 25
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 59
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 31
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 28
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 21
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 claims description 12
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 12
- VLLNJDMHDJRNFK-UHFFFAOYSA-N adamantan-1-ol Chemical compound C1C(C2)CC3CC2CC1(O)C3 VLLNJDMHDJRNFK-UHFFFAOYSA-N 0.000 claims description 12
- CFXQEHVMCRXUSD-UHFFFAOYSA-N 1,2,3-Trichloropropane Chemical compound ClCC(Cl)CCl CFXQEHVMCRXUSD-UHFFFAOYSA-N 0.000 claims description 10
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 61
- 238000004458 analytical method Methods 0.000 description 19
- 238000000034 method Methods 0.000 description 19
- 230000000052 comparative effect Effects 0.000 description 9
- 230000035484 reaction time Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- IYKFYARMMIESOX-SPJNRGJMSA-N adamantanone Chemical compound C([C@H](C1)C2)[C@H]3C[C@@H]1C(=O)[C@@H]2C3 IYKFYARMMIESOX-SPJNRGJMSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QVLAWKAXOMEXPM-UHFFFAOYSA-N 1,1,1,2-tetrachloroethane Chemical compound ClCC(Cl)(Cl)Cl QVLAWKAXOMEXPM-UHFFFAOYSA-N 0.000 description 2
- QXSZNDIIPUOQMB-UHFFFAOYSA-N 1,1,2,2-tetrabromoethane Chemical compound BrC(Br)C(Br)Br QXSZNDIIPUOQMB-UHFFFAOYSA-N 0.000 description 2
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000001256 steam distillation Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- GNYRTKBEORFHLK-UHFFFAOYSA-N BrCCBr.ClCC(CCl)Cl Chemical compound BrCCBr.ClCC(CCl)Cl GNYRTKBEORFHLK-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 229940052761 dopaminergic adamantane derivative Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012770 industrial material Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 229910001507 metal halide Inorganic materials 0.000 description 1
- 150000005309 metal halides Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000013307 optical fiber Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 229920002120 photoresistant polymer Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明は、医農薬原料、産業用原料として重要な中間体である２−アダマンタノンを硫酸を用いて効率的に製造する方法に関するものである。 The present invention relates to a method for efficiently producing 2-adamantanone, which is an important intermediate as a raw material for medicines and agricultural chemicals and industrial materials, using sulfuric acid.
アダマンタンは、ダイヤモンド構造単位と同じ構造を持つ、対称性の高いカゴ型化合物として知られている。
化学物質としては、（１）分子の歪みエネルギーが少なく、熱安定性に優れ、（２）炭素密度が大きいため脂溶性が大きく、（３）昇華性があるにもかかわらず、臭いが少ないなどの特徴を有しており、１９８０年代からは医薬品分野においてパーキンソン氏病治療薬、インフルエンザ治療薬原料として注目されていたが、近年アダマンタン誘導体の有する耐熱性や透明性などの特性が、半導体製造用フォトレジスト、磁気記録媒体、光ファイバー、光学レンズ、光ディスク基板原料などの光学材料や、耐熱性プラスティック、塗料、接着剤などの機能性材料、化粧品などの分野で注目され、その用途が増大しつつある。
また、医薬分野においても抗癌剤、脳機能改善、神経性疾患、抗ウイルス剤原料としての需要が増大してきている。
Adamantane is known as a highly symmetrical cage compound having the same structure as the diamond structural unit.
Chemical substances include (1) low molecular strain energy, excellent thermal stability, (2) high fat solubility due to high carbon density, and (3) low odor despite sublimation. Since the 1980s, it has attracted attention as a raw material for treating Parkinson's disease and influenza in the pharmaceutical field. In recent years, the properties of adamantane derivatives such as heat resistance and transparency have been It is attracting attention in the fields of optical materials such as photoresists, magnetic recording media, optical fibers, optical lenses, and optical disk substrates, functional materials such as heat-resistant plastics, paints, and adhesives, and cosmetics, and its applications are increasing. .
In the pharmaceutical field, the demand for anticancer agents, brain function improvement, neurological diseases, and antiviral materials is increasing.
炭化水素化合物を酸化してアルコールやケトンに変換する技術は、炭素資源の有効活用の観点から、工業的にも非常に重要な技術である。
２−アダマンタノンを選択的に製造する技術としては、濃硫酸中で製造する方法が公知である。
例えば、シュラットマン（Ｓｃｈｌａｔｍａｎｎ）は、１−アダマンタノールを濃硫酸中、３０℃で１２時間加熱反応させることにより、２−アダマンタノンが収率７２％で得られることを報告している（非特許文献１参照）。
また、アダマンタンを濃硫酸により酸化した後、水蒸気蒸留により精製することにより、アダマンタノンが収率４７〜４８％で得られることも知られている（非特許文献２参照）。
従って、硫酸を用いた通常の製造方法では、重質分が副生しアダマンタノン収率が十分とは言えない。
Technology for oxidizing hydrocarbon compounds to convert them to alcohols and ketones is a very important technology from the viewpoint of effective utilization of carbon resources.
As a technique for selectively producing 2-adamantanone, a method for producing it in concentrated sulfuric acid is known.
For example, Schlatmann reports that 2-adamantanone can be obtained in a yield of 72% by reacting 1-adamantanol in concentrated sulfuric acid at 30 ° C. for 12 hours (non-patent document). Reference 1).
It is also known that adamantane is obtained in a yield of 47 to 48% by oxidizing adamantane with concentrated sulfuric acid and then purifying by steam distillation (see Non-Patent Document 2).
Therefore, in a normal production method using sulfuric acid, heavy components are by-produced and it cannot be said that the adamantanone yield is sufficient.
上記技術の改良法として、反応を２段階又は３段階で昇温して実施する方法が提案されている（特許文献１及び２参照）。
しかし、これらの方法は、アダマンタノンの収率が最高９０％に向上するものの、反応速度が遅く、３０時間以上の長時間を必要とするという問題点がある。
As an improved method of the above technique, a method of carrying out the reaction by raising the temperature in two or three stages has been proposed (see Patent Documents 1 and 2).
However, these methods have a problem that the reaction rate is slow and a long time of 30 hours or more is required although the yield of adamantanone is improved to 90% at the maximum.
また、反応中に三酸化硫黄又は発煙硫酸を添加して、硫酸濃度の低下を抑制する方法も提案されている（特許文献３〜５参照）。
しかし、これらの方法は、アダマンタノンの収率が最高９２％に向上するものの、取り扱いが難しい三酸化硫黄又は発煙硫酸を使用する必要がある。
更に、硫酸ナトリウム等の無機塩（特許文献６参照）、五酸化リン等の乾燥剤（特許文献７参照）、ヨウ素等のハロゲン単体又はヨウ化カリウム等のハロゲン化金属（特許文献８参照）を反応系に添加する方法も提案されている。
しかし、これらの方法は、アダマンタノンの収率は向上する（特許文献７で最高９３％）ものの、特許文献６の方法では反応速度が遅く、３０時間以上の長時間を必要とし、特許文献７〜８の方法では添加物を含んだ廃硫酸の処理が煩雑であり、工業的な利用は難しい。
更に、酸素存在下、超音波を作用させる方法（特許文献９参照）も提案されているが、設備に多大な費用がかかることが予想され、工業的な実施は困難であると考えられる。
In addition, a method has been proposed in which sulfur trioxide or fuming sulfuric acid is added during the reaction to suppress a decrease in sulfuric acid concentration (see Patent Documents 3 to 5).
However, these methods require the use of sulfur trioxide or fuming sulfuric acid which is difficult to handle, although the yield of adamantanone is improved up to 92%.
Further, an inorganic salt such as sodium sulfate (see Patent Document 6), a desiccant such as phosphorus pentoxide (see Patent Document 7), a halogen simple substance such as iodine, or a metal halide such as potassium iodide (see Patent Document 8). A method of adding to the reaction system has also been proposed.
However, these methods improve the yield of adamantanone (up to 93% in Patent Document 7), but the method of Patent Document 6 has a slow reaction rate and requires a long time of 30 hours or more. In the methods (8) to (8), the treatment of waste sulfuric acid containing additives is complicated and industrial use is difficult.
Furthermore, a method of applying ultrasonic waves in the presence of oxygen (see Patent Document 9) has also been proposed, but it is expected that the equipment will be very expensive, and industrial implementation is considered difficult.
硫酸を用いる上記反応を有機溶媒中で実施することも可能であり、反応を阻害せず、原料化合物を溶解する有機溶媒が何等制限なく使用でき、特に高い収率が期待できる、塩化メチレン、クロロホルム等のハロゲン化脂肪族炭化水素類、ジクロロベンゼン等のハロゲン化芳香族炭化水素類が好適に採用される（特許文献２、４〜８参照）と記載されているが実施例はなく、今日まで特許文献２、４〜８以外にも有機溶媒を用いた実施例は知られていない。 It is also possible to carry out the above reaction using sulfuric acid in an organic solvent, an organic solvent that does not inhibit the reaction and dissolves the raw material compound can be used without any limitation, and a particularly high yield can be expected. Methylene chloride, chloroform And halogenated aromatic hydrocarbons such as dichlorobenzene are suitably employed (see Patent Documents 2 and 4 to 8), but no examples are available. Other than Patent Documents 2 and 4 to 8, examples using an organic solvent are not known.
硫酸を用いた製造方法は、安価で工業的に入手が容易な硫酸を用い、特殊な反応設備を必要としないという観点から、工業的に魅力のある製造方法ではある。
しかし、その反応速度及びアダマンタノンの収率は十分とは云えず、更なる改良が要求されている。
The manufacturing method using sulfuric acid is an industrially attractive manufacturing method from the viewpoint of using sulfuric acid which is inexpensive and easily available industrially and does not require special reaction equipment.
However, the reaction rate and the yield of adamantanone are not sufficient, and further improvement is required.
本発明は、硫酸を用いる製造方法の特長を損なうことなく、アダマンタン及び／又は１−アダマンタノールより高選択率で２−アダマンタノンを製造する方法を提供することを目的とするものである。 An object of the present invention is to provide a method for producing 2-adamantanone with higher selectivity than adamantane and / or 1-adamantanol without impairing the characteristics of the production method using sulfuric acid.
本発明者らは、鋭意研究を続けた結果、アダマンタン及び／又は１−アダマンタノールを硫酸により酸化して２−アダマンタノンを製造する方法において、特定のハロゲン化アルカンを共存させることにより、上記目的を達成しうることを見出した。
本発明はかかる知見に基づいて完成したものである。
As a result of continual research, the inventors of the present invention have made the above object by allowing a specific halogenated alkane to coexist in a method for producing 2-adamantanone by oxidizing adamantane and / or 1-adamantanol with sulfuric acid. It was found that can be achieved.
The present invention has been completed based on such findings.
すなわち、本発明は、
１．アダマンタン及び／又は１−アダマンタノールを硫酸により酸化して２−アダマンタノンを製造する方法において、２つの一級炭素のそれぞれに少なくとも１つのハロゲン原子が結合している炭素数２〜５のハロゲン化アルカンの存在下で、硫酸酸化することを特徴とする２−アダマンタノンの製造方法、
２．ハロゲン化アルカンの使用量が、アダマンタン及び／又は１−アダマンタノール１質量部に対して０．５〜１００質量部である上記１に記載の２−アダマンタノンの製造方法、３．ハロゲン化アルカンが、塩素化アルカンである上記１又は２に記載の２−アダマンタノンの製造方法、
４．塩素化アルカンが、１，２−ジクロロエタン、１，１，２−トリクロロエタン、１，１，２，２−テトラクロロエタン、１，３−ジクロロプロパン及び１，２，３−トリクロロプロパンから選ばれる少なくとも一種である上記１〜３のいずれかに記載の２−アダマンタノンの製造方法
に関するものである。
That is, the present invention
1. In a method for producing 2-adamantanone by oxidizing adamantane and / or 1-adamantanol with sulfuric acid, a halogenated alkane having 2 to 5 carbon atoms in which at least one halogen atom is bonded to each of two primary carbons A method for producing 2-adamantanone, characterized by subjecting to sulfuric acid oxidation in the presence of
2. 2. The method for producing 2-adamantanone according to 1 above, wherein the amount of halogenated alkane used is 0.5 to 100 parts by mass with respect to 1 part by mass of adamantane and / or 1-adamantanol. The method for producing 2-adamantanone according to 1 or 2, wherein the halogenated alkane is a chlorinated alkane,
4). The chlorinated alkane is at least one selected from 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, 1,3-dichloropropane and 1,2,3-trichloropropane. It is related with the manufacturing method of 2-adamantanone in any one of said 1-3 which is.
本発明によれば、アダマンタン及び／又は１−アダマンタノールを硫酸を用いて酸化することにより、工業的に容易に実施可能な簡便な方法で、高選択率で２−アダマンタノンを製造することができる。 According to the present invention, by oxidizing adamantane and / or 1-adamantanol with sulfuric acid, 2-adamantanone can be produced with high selectivity by a simple method that can be easily carried out industrially. it can.
以下、本発明を詳細に説明する。
本発明の原料として用いるアダマンタン、１−アダマンタノールは、単独でも又は混合して反応に供することができる。
本発明で用いる硫酸の濃度としては、特に制限はないが、通常、硫酸の濃度は９５〜１００質量％、好ましくは９７〜１００質量％、より好ましくは９８〜１００質量％である。
硫酸の濃度が上記範囲内であると、副生する水による反応速度の低下が抑制され、更に重質分の生成を抑えることができる。
硫酸の使用量としては、特に制限はないが、通常、アダマンタン及び／又は１−アダマンタノール１質量部に対し０．１〜１５０質量部、好ましくは１〜１００質量部、より好ましくは２〜５０質量部である。
硫酸の使用量が上記範囲内であると、反応が円滑に進行し、硫酸の後処理が容易である。
すなわち、硫酸の使用量が０．１質量部未満であると反応が十分に進行せず、１５０質量部を超えると硫酸の処理量が大量になり、後処理に時間がかかり、２−アダマンタノンの生産効率が悪化する。
Hereinafter, the present invention will be described in detail.
The adamantane and 1-adamantanol used as the raw material of the present invention can be used alone or mixed for the reaction.
Although there is no restriction | limiting in particular as a density | concentration of the sulfuric acid used by this invention, Usually, the density | concentration of a sulfuric acid is 95-100 mass%, Preferably it is 97-100 mass%, More preferably, it is 98-100 mass%.
When the concentration of sulfuric acid is within the above range, a decrease in reaction rate due to by-produced water is suppressed, and further generation of heavy components can be suppressed.
Although there is no restriction | limiting in particular as the usage-amount of a sulfuric acid, 0.1-150 mass parts normally with respect to 1 mass part of adamantane and / or 1-adamantanol, Preferably it is 1-100 mass parts, More preferably, it is 2-50. Part by mass.
When the amount of sulfuric acid used is within the above range, the reaction proceeds smoothly and post-treatment of sulfuric acid is easy.
That is, when the amount of sulfuric acid used is less than 0.1 parts by mass, the reaction does not proceed sufficiently, and when it exceeds 150 parts by mass, the amount of sulfuric acid processed becomes large and post-treatment takes time, and 2-adamantanone The production efficiency will deteriorate.
本発明で用いる２つの一級炭素のそれぞれに少なくとも１つのハロゲン原子が結合している炭素数２〜５のハロゲン化アルカン（以下、ハロゲン化アルカンと呼称することがある）の具体例としては、１，２−ジクロロエタン、１，１，２−トリクロロエタン、１，１，２，２−テトラクロロエタン、１，１，１，２−テトラクロロエタン、１，３−ジクロロプロパン、１，２，３−トリクロロプロパン、１，２−ジブロモエタン、１，１，２，２−テトラブロモエタン、２−ブロモ−１−クロロエタン等が挙げられる。
上記ハロゲン化アルカンは、一種を用いてもよく、混合して用いてもよい。
ハロゲン化アルカンは、好ましくは炭素数２〜３のハロゲン化アルカン、より好ましくは炭素数２〜３の塩素化アルカンである。
炭素数２〜３の塩素化アルカンの具体例としては、１，２−ジクロロエタン、１，１，２−トリクロロエタン、１，１，２，２−テトラクロロエタン、１，３−ジクロロプロパン、１，２，３−トリクロロプロパン等が挙げられる。
本発明のハロゲン化アルカンの使用量としては、特に制限はないが、通常、アダマンタン及び／又は１−アダマンタノール１質量部に対し、０．５〜１００質量部、好ましくは０．５〜１０質量部、より好ましくは１．０〜１０質量部である。
ハロゲン化アルカンの使用量が上記範囲内であると、２−アダマンタノンの収率が上昇し、生産効率が向上する。
すなわち、ハロゲン化アルカンの使用量が０．５質量部未満であると２−アダマンタノンの収率が低下し、１００質量部を超えると反応器への仕込み量が増大するため生産効率が悪化する。
Specific examples of the halogenated alkane having 2 to 5 carbon atoms in which at least one halogen atom is bonded to each of the two primary carbons used in the present invention (hereinafter sometimes referred to as a halogenated alkane) include 1 , 2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, 1,1,1,2-tetrachloroethane, 1,3-dichloropropane, 1,2,3-trichloropropane 1,2-dibromoethane, 1,1,2,2-tetrabromoethane, 2-bromo-1-chloroethane and the like.
The halogenated alkanes may be used singly or as a mixture.
The halogenated alkane is preferably a halogenated alkane having 2 to 3 carbon atoms, more preferably a chlorinated alkane having 2 to 3 carbon atoms.
Specific examples of the chlorinated alkane having 2 to 3 carbon atoms include 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, 1,3-dichloropropane, 1,2 , 3-trichloropropane and the like.
Although there is no restriction | limiting in particular as the usage-amount of the halogenated alkane of this invention, Usually, 0.5-100 mass parts with respect to 1 mass part of adamantane and / or 1-adamantanol, Preferably it is 0.5-10 mass. Part, more preferably 1.0 to 10 parts by mass.
If the amount of halogenated alkane used is within the above range, the yield of 2-adamantanone increases and the production efficiency improves.
That is, if the amount of halogenated alkane used is less than 0.5 parts by mass, the yield of 2-adamantanone decreases, and if it exceeds 100 parts by mass, the amount charged to the reactor increases and production efficiency deteriorates. .
本発明の反応温度としては、特に制限はないが、通常、２０〜１５０℃、好ましくは３０〜１２０℃、より好ましくは４０〜１００℃である。
反応温度が上記範囲内であると、反応時間が適度で、重質分の副生を抑制することができ、２−アダマンタノンの収率が向上する。
すなわち、反応温度が２０℃未満であると反応速度が低下して生産効率が悪化し、１５０℃を超えると重質分の副生が増加し、２−アダマンタノンの選択率が低下する。
Although there is no restriction | limiting in particular as reaction temperature of this invention, Usually, 20-150 degreeC, Preferably it is 30-120 degreeC, More preferably, it is 40-100 degreeC.
When the reaction temperature is within the above range, the reaction time is moderate, by-products of heavy components can be suppressed, and the yield of 2-adamantanone is improved.
That is, when the reaction temperature is less than 20 ° C., the reaction rate decreases and the production efficiency deteriorates. When the reaction temperature exceeds 150 ° C., the by-product of the heavy component increases and the selectivity for 2-adamantanone decreases.
反応時間は、反応温度によっても異なるが、通常、０．５〜２４時間、好ましくは１〜１２時間、より好ましくは２〜１０時間である。
反応時間が上記範囲内であると、反応が円滑に進行し２−アダマンタノンの生産効率が向上する。
すなわち、反応時間が０．５時間未満であると反応が十分進行せず、２４時間を越えると２−アダマンタノンの生産効率が低下する。
The reaction time varies depending on the reaction temperature, but is usually 0.5 to 24 hours, preferably 1 to 12 hours, more preferably 2 to 10 hours.
When the reaction time is within the above range, the reaction proceeds smoothly and the production efficiency of 2-adamantanone is improved.
That is, when the reaction time is less than 0.5 hours, the reaction does not proceed sufficiently, and when it exceeds 24 hours, the production efficiency of 2-adamantanone decreases.
本発明の硫酸を用いる製造方法においては、反応中に亜硫酸ガスが発生するため、通常、反応は常圧で行われるが、減圧、加圧のいずれの状態でも反応を実施することができる。
本発明に用いる反応装置としては、十分な撹拌が可能で且つ硫酸、ハロゲン化アルカン等に耐える材質を使用した装置あれば、何ら制限はないが、通常、ガラスライニングされた装置が用いられる。
本発明は、通常、反応容器に所定量のアダマンタン及び／又は１−アダマンタノール、所定量の所定の濃度に調製した硫酸、所定量のハロゲン化アルカンを仕込み、反応条件を設定して反応を行う。
反応終了後の反応液からの２−アダマンタノンの単離方法としては、特に制限はないが、例えば、反応液を氷中に投入して、中和後析出した結晶を溶媒により抽出し、次いで洗浄、溶媒留去及び乾燥を行う方法、反応液を氷中に投入して、中和後析出した結晶をろ過及び遠心分離する方法等が挙げられる。
上記抽出溶媒としては、反応に使用した本発明のハロゲン化アルカンと同一のハロゲン化アルカンを使用することができ、具体例としては、１，２−ジクロロエタン、１，１，２−トリクロロエタン、１，１，２，２−テトラクロロエタン、１，１，１，２−テトラクロロエタン、１，３−ジクロロプロパン、１，２，３−トリクロロプロパン、１，２−ジブロモエタン、１，１，２，２−テトラブロモエタン、２−ブロモ−１−クロロエタン等が挙げられる。
このようにして得られた２−アダマンタノンは、必要により、クロマトグラフィ、再結晶、減圧蒸留、水蒸気蒸留又は昇華精製などの方法で精製することができる。
In the production method using sulfuric acid of the present invention, since sulfurous acid gas is generated during the reaction, the reaction is usually carried out at normal pressure, but the reaction can be carried out in either reduced pressure or pressurized state.
The reaction apparatus used in the present invention is not limited as long as it is an apparatus that can sufficiently stir and uses a material that can withstand sulfuric acid, halogenated alkane, and the like, but a glass-lined apparatus is usually used.
In the present invention, a reaction vessel is usually charged with a predetermined amount of adamantane and / or 1-adamantanol, a predetermined amount of sulfuric acid adjusted to a predetermined concentration, and a predetermined amount of halogenated alkane, and the reaction is carried out by setting reaction conditions. .
The method for isolating 2-adamantanone from the reaction solution after completion of the reaction is not particularly limited. For example, the reaction solution is poured into ice, and the crystals precipitated after neutralization are extracted with a solvent. Examples thereof include a method of washing, distilling off the solvent and drying, a method of putting the reaction solution into ice, and filtering and centrifuging the crystals precipitated after neutralization.
As the extraction solvent, the same halogenated alkane as the halogenated alkane of the present invention used in the reaction can be used. Specific examples include 1,2-dichloroethane, 1,1,2-trichloroethane, 1, 1,2,2-tetrachloroethane, 1,1,1,2-tetrachloroethane, 1,3-dichloropropane, 1,2,3-trichloropropane, 1,2-dibromoethane, 1,1,2,2 -Tetrabromoethane, 2-bromo-1-chloroethane and the like.
The 2-adamantanone thus obtained can be purified by a method such as chromatography, recrystallization, vacuum distillation, steam distillation or sublimation purification, if necessary.
以下に、本発明を実施例により具体的に説明するが、本発明はこれらに制限されるものではない。 EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
実施例1
５０ｍＬのフラスコにアダマンタン１ｇ、９８質量％硫酸１１ｇ及び１，２−ジクロロエタン５ｇを仕込んだ。
攪拌しながら、６０℃まで昇温し、６０℃になってから、8時間反応を行った。
反応終了後、５０ｇの氷に反応液を注ぎ、ｐＨ９になるまで５０質量％水酸化ナトリウム水溶液を加えた。
次に、トルエン５０ｍＬで抽出し、抽出液をガスクロマトグラフィを用いて分析した。
得られた結果を表１に示す。
Example 1
A 50-mL flask was charged with 1 g of adamantane, 11 g of 98% by mass sulfuric acid and 5 g of 1,2-dichloroethane.
While stirring, the temperature was raised to 60 ° C., and the reaction was carried out for 8 hours after reaching 60 ° C.
After completion of the reaction, the reaction solution was poured into 50 g of ice, and 50% by mass aqueous sodium hydroxide solution was added until pH 9 was reached.
Next, extraction was performed with 50 mL of toluene, and the extract was analyzed using gas chromatography.
The obtained results are shown in Table 1.
実施例２
１，２−ジクロロエタンの代わりに１，１，２−トリクロロエタンを用いた以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例３
１，２−ジクロロエタンの代わりに１，１，２，２−テトラクロロエタンを用いた以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例４
１，２−ジクロロエタンの代わりに１，３−ジクロロプロパンを用いた以外は、実施例1と同様と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Example 2
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,1,2-trichloroethane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
Example 3
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,1,2,2-tetrachloroethane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
Example 4
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,3-dichloropropane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
実施例5
１，２−ジクロロエタンの代わりに１，２，３−トリクロロプロパンを用いた以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例６
９８質量％硫酸の量を５．５ｇとし、反応時間を１６時間とした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例７
１，２−ジクロロエタンの量を０．５ｇにした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Example 5
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,2,3-trichloropropane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
Example 6
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the amount of 98% by mass sulfuric acid was 5.5 g and the reaction time was 16 hours.
The results are shown in Table 1.
Example 7
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the amount of 1,2-dichloroethane was changed to 0.5 g.
The results are shown in Table 1.
実施例８
１，２−ジクロロエタンの量を１．０ｇにした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例９
１，２−ジクロロエタンの量を２．５ｇにした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例１０
反応温度を４０℃とし、反応時間を２４時間にした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Example 8
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the amount of 1,2-dichloroethane was changed to 1.0 g.
The results are shown in Table 1.
Example 9
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the amount of 1,2-dichloroethane was changed to 2.5 g.
The results are shown in Table 1.
Example 10
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the reaction temperature was 40 ° C. and the reaction time was 24 hours.
The results are shown in Table 1.
実施例１１
反応温度を５０℃にし、反応時間を１６時間にした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
実施例１２
反応温度を７０℃とし、反応時間を4時間にした以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Example 11
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the reaction temperature was 50 ° C. and the reaction time was 16 hours.
The results are shown in Table 1.
Example 12
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the reaction temperature was 70 ° C. and the reaction time was 4 hours.
The results are shown in Table 1.
比較例１
１，２−ジクロロエタンの代わりにジクロロメタンを用いた以外は、実施例９と同様に反応、後処理及び分析を行った。
結果を表1に示す。
比較例２
１，２−ジクロロエタンの代わりにクロロホルムを用いた以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
比較例３
１，２−ジクロロエタンの代わりに１，１−ジクロロエタンを用いた以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Comparative Example 1
The reaction, post-treatment and analysis were performed in the same manner as in Example 9 except that dichloromethane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
Comparative Example 2
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that chloroform was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
Comparative Example 3
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,1-dichloroethane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
比較例４
１，２−ジクロロエタンの代わりに１，２−ジクロロプロパンを用いた以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
比較例５
１，２−ジクロロエタンを添加しなかった以外は、実施例1と同様に反応、後処理及び分析を行った。
結果を表1に示す。
比較例６
１，２−ジクロロエタンを添加しなかった以外は、実施例6と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Comparative Example 4
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,2-dichloropropane was used instead of 1,2-dichloroethane.
The results are shown in Table 1.
Comparative Example 5
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that 1,2-dichloroethane was not added.
The results are shown in Table 1.
Comparative Example 6
The reaction, post-treatment and analysis were performed in the same manner as in Example 6 except that 1,2-dichloroethane was not added.
The results are shown in Table 1.
比較例７
１，２−ジクロロエタンの量を０．０５ｇにした以外は、実施例１と同様に反応、後処理及び分析を行った。
結果を表1に示す。
比較例８
１，２−ジクロロエタンの量を０．１ｇにした以外は、実施例１と同様に反応、後処理及び分析を行った。
結果を表1に示す。
Comparative Example 7
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the amount of 1,2-dichloroethane was changed to 0.05 g.
The results are shown in Table 1.
Comparative Example 8
The reaction, post-treatment and analysis were performed in the same manner as in Example 1 except that the amount of 1,2-dichloroethane was changed to 0.1 g.
The results are shown in Table 1.
表１から明らかなように、本発明のハロゲン化アルカンを反応系に共存させた実施例では、短時間且つ高収率で２−アダマンタノンを製造することができる。
また、硫酸量を低減しても２−アダマンタノン収率が低下しない。
これに対し、ハロゲン化アルカンを反応系に添加しないか、本発明の範囲外のハロゲン化アルカンを反応系に共存させた比較例では、短時間且つ高収率で２−アダマンタノンを製造することができない。
As is apparent from Table 1, in the example in which the halogenated alkane of the present invention was allowed to coexist in the reaction system, 2-adamantanone can be produced in a short time and in a high yield.
Moreover, even if the amount of sulfuric acid is reduced, the yield of 2-adamantanone does not decrease.
In contrast, in the comparative example in which the halogenated alkane was not added to the reaction system or the halogenated alkane outside the scope of the present invention was allowed to coexist in the reaction system, 2-adamantanone was produced in a short time and in a high yield. I can't.
本発明は、医農薬原料、産業用原料等として重要な中間体である２−アダマンタノンを簡便に得る方法を提供する。 The present invention provides a method for easily obtaining 2-adamantanone, which is an important intermediate as a raw material for medicines and agricultural chemicals, industrial raw materials and the like.
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| JP3772009B2 (en) * | 1997-12-26 | 2006-05-10 | 株式会社トクヤマ | Method for producing adamantanone |
| JP2002145820A (en) * | 2000-11-09 | 2002-05-22 | Mitsubishi Chemicals Corp | Method for producing 2-adamantanone |
| JP3998966B2 (en) * | 2001-12-21 | 2007-10-31 | 株式会社トクヤマ | Method for producing adamantanols |
| JP4065689B2 (en) * | 2001-12-27 | 2008-03-26 | 株式会社トクヤマ | 2-Adamantanone production method |
| JP4038657B2 (en) * | 2002-01-16 | 2008-01-30 | 三菱瓦斯化学株式会社 | Method for producing adamantanone |
| JP2005097201A (en) * | 2003-09-26 | 2005-04-14 | Tokuyama Corp | Method for producing alicyclic ketone compound |
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