1225857 A7 B7 五、發明説明（j 技術領域 (請先閱讀背面之注意事項再填寫本頁) 本發明係有關可有效率以高收穫率由取代或非取代2 -金剛酮製造具有金剛烷架構之第三醇的方法。 背景技術 近年來積極開發金剛酮衍生物於各種領域上之用途， 如以2 -乙基金剛醇爲光阻原料。 目前有關金剛酮衍生物之烷基化係使用格利雅試劑等 鎂化合物，因此除了目的之烷基化物外，主要會生成還原 醇。例如已知2 -金剛酮與乙基格利雅試劑反應時，主要 因酮本身之容積較高，故除了 2 -乙基金剛醇外，會大量 生成金剛酮還原之2 -金剛醇〔2 -乙基金剛醇收穫率 4 0%:[人111.0^111.8〇(：.，\^〇1.9，1^〇.13,4248至 4634頁（1972 ) ]° 又，使用乙基鋰製造第三醇時雖不會生成還原物，但 ，試劑貴且難處理有危險性。 經濟部智慧財產局員工消費合作社印製 已知共存氯化鈽下使酮類與格利雅試劑反應時，可抑 制還原物生成等異常反應。例如共存氯化鈽下，利用格利 雅試劑進行二異丙基銅之異丙基化時，可將不使用氯化姉 時所生成之附加物3%大幅提升至5 2%，但，會生成某 種程度（3 1 % )還原物〔Tetrahedron Lett.:Vol.26，No.39, 4763至 4766 頁（1 985)〕。 發明揭示 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） -4- 12258571225857 A7 B7 V. Description of the invention (j Technical field (please read the notes on the back before filling this page) The present invention relates to the efficient and high-yield production of substituted or non-substituted 2-adamantanone with an adamantane structure. Method for the third alcohol. BACKGROUND ART In recent years, the use of amantadone derivatives in various fields has been actively developed, such as 2-ethyladamantanol as a photoresist raw material. Currently, Griya is used for the alkylation of amantadone derivatives. Magnesium compounds such as reagents, in addition to the intended alkylate, mainly generate reduced alcohols. For example, it is known that when 2-adamantanone reacts with ethyl Grignard reagent, mainly because the ketone itself has a high volume, in addition to 2-ethyl In addition to memantine, a large amount of 2-adamantanol [2-ethyladamantanol yield [40%]: [human 111.0 ^ 111.8〇 (: ,, \ ^ 〇1.9, 1 ^ 〇.13, Pages 4248 to 4634 (1972)] Although the use of ethyl lithium for the production of tertiary alcohols does not produce reductants, the reagents are expensive and difficult to handle, which is dangerous. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Coexistence of ketones with lattice When the reagent is reacted, it can suppress abnormal reactions such as the formation of reduced products. For example, in the coexistence of gadolinium chloride, the isopropylation of diisopropyl copper using Grignard reagent, the additional The amount of 3% is increased to 5 2%, but a certain amount (3 1%) of the reduced product [Tetrahedron Lett .: Vol. 26, No. 39, 4763 to 4766 (1 985)] is produced. Paper size applies to China National Standard (CNS) A4 specification (210X297 mm) -4- 1225857
爲了解決上述目前之技術問題，故本發明之目的爲， ί疋供種使取代或非取代2 -金剛酮院基化以製造第三醇 時，可明藏抑制還原物生成及以高收穫率有效且廉價製造 加物之方法。 經本發明者專心硏究後發明，共存稀土類鹵化物下使 取代或非取代2 -金剛酮與格利雅試劑反應時，可明顯抑 制還原物生成，而完成本發明。 即’本發明係提供具有一般式（I )所示金剛烷架構 之第二醇的製造方法，其特徵爲，製造一般式（j ) (請先閲讀背面之注意事項再填寫本頁)In order to solve the above-mentioned current technical problems, the purpose of the present invention is to prevent the formation of reduced substances and to obtain high yields when the seed is used to form a substituted or non-substituted 2-adamantanone to produce a third alcohol. Efficient and inexpensive method for manufacturing additives. The present inventors have devoted intensive research and invented that the reaction of substituted or unsubstituted 2-adamantanone with Grignard reagent under the coexistence of rare earth halides can significantly suppress the formation of reduced products, and completed the present invention. That is, the present invention provides a method for producing a second alcohol having an adamantane structure represented by the general formula (I), which is characterized by manufacturing the general formula (j) (please read the precautions on the back before filling in this page)
RR
經濟部智慧財產局員工消費合作社印製Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs
(丫)η 〔式中’ R爲碳數2至1 0具有/3氫之烷基；Y爲氫原子 ’鹵原子，碳數1至1 0之烷基，碳數1至1 〇之烷氧基 ’縮酮，矽烷基或3取代胺基；η爲1至5之整數〕所示 金剛烷化合物之第三醇時，係於存在稀土類鹵化物下，使 一般式（I I ) (II) 本紙張尺度適用中.國國家標準（CNS ) Α4規格（210Χ29?公釐） -5- 經濟部智慧財產局員工消費合作社印製 1225857 A7 ---------—_____ B7 五、發明説明（$ ""〜"一' --- 〔式中’ Y及η同上述〕所示取彳 取代或非取代2 -金剛酮化 合物與一般式（I I I ) R M g X ( I I I ) 〔式中，R爲具有石氫之碳數2至1〇的烷基；又爲_原 子〕所示鎂化合物或二烷基鎂化合物反應。 實施發明之最佳形態 本發明係有關製造一般式（I )所示具有金剛烷架構 之第三醇，其中，一般式（丨）之R係來自格利雅試劑的 碳數2至1 〇具有氫之烷基，例如乙基，丙基等，γ爲 氫原子或各種取代基，例如鹵原子，碳數1至1 〇之烷基 (例如曱基，乙基等），碳數1至1 0之烷氧基（例如甲 氧基，乙氧基等），縮酮基（二甲基縮酮基等），矽烷基 (三甲基矽烷基等）或3取代胺基（三甲基胺基等）。 本發明之一般式（I )所示第三醇之具體例如，2 -乙基金剛院一 2 -醇’ 1 一甲基一 2 —乙基金剛院一 2 -醇，1—甲基—2 -丙基金剛烷—2 -醇，1 一甲基—2 -丁基金剛烷—2 —醇，1，3 —二甲基—2 -乙基金剛 烷一 2 -醇，1，3 —二甲基一 2 -丁基金剛烷一 2 -醇 ，1 一氯一 2 —乙基金剛院一 2 —醇，1 一三甲基石夕院基 —2 -乙基金剛烷—2 —醇等。 本發明之方法中，一般式（I )所示具有金剛院架構 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） (請先閱讀背面之注意事項再填寫本頁)(Γ) η [wherein R is an alkyl group having 2 to 10 carbon atoms and / 3 hydrogen; Y is a hydrogen atom 'halogen atom, an alkyl group having 1 to 10 carbon atoms, and an alkyl group having 1 to 10 carbon atoms Oxy 'ketal, silane or 3 substituted amine; η is an integer of 1 to 5] when the third alcohol of the adamantane compound is in the presence of a rare earth halide, the general formula (II) (II ) This paper size is applicable. National National Standard (CNS) Α4 specification (210 × 29? Mm) -5- Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1225857 A7 ---------—____ B7 V. Description of the invention ($ " " ~ " a '--- [wherein Y and η are the same as described above] take 彳 substituted or unsubstituted 2 -adamantanone compound with general formula (III) RM g X (III ) [Wherein, R is an alkyl group having 2 to 10 carbon atoms with stone hydrogen; and _atom] is reacted with a magnesium compound or a dialkyl magnesium compound. Best Mode for Carrying Out the Invention The present invention relates to general manufacturing A tertiary alcohol having an adamantane structure as shown in formula (I), in which R of the general formula (丨) is derived from a Grignard reagent having 2 to 10 carbon atoms having hydrogen, such as ethyl Propyl, etc., γ is a hydrogen atom or various substituents, such as a halogen atom, an alkyl group having 1 to 10 carbon atoms (such as fluorenyl, ethyl, etc.), and an alkoxy group having 1 to 10 carbon atoms (such as methoxy Group, ethoxy group, etc.), ketal group (dimethyl ketal group, etc.), silane group (trimethylsilyl group, etc.) or 3-substituted amino group (trimethylamino group, etc.). Specific examples of the third alcohol shown in (I) include 2-ethyladamantine-2-alcohol '1-methyl-2 2-ethyladamantine- 2-alcohol, 1-methyl-2-propyladamantane —2 -alcohol, 1-methyl-2-butanebutane-2—alcohol, 1,3-dimethyl-2—ethyladamantane-2—alcohol, 1,3-dimethyl-2— Butanyl adamantane-2-ol, 1 chloro-2 2-ethyladamantane-1 2-alcohol, 1-trimethylstilbene 2- 2-ethyladamantane-2 -alcohol, etc. In the method of the present invention , The general formula (I) has the King Kong Institute structure. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the precautions on the back before filling this page)
-6 - 1225857 經濟部智慧財產局員工消費合作社印製 Α7 Β7 五、發明説明（4 之第三醇係由，存在稀土類鹵化物下使一般式（I〗）所 示取代或非取代2 -金剛酮化合物與一般式（丨I J ) R M g X (III) 〔式中，R爲具有/3氫之碳數2至1 〇的烷基；又爲齒原 子〕所示鎂化合物或二烷基鎂化合物反應而製得。 該一般式（I I I )所示鎂化合物爲一般之格利雅式 劑。又，二烷基鎂化合物如，二甲基鎂，二乙基鎂，二τ 基鎂等。 鎂化合物對一般式（I I )所示取代或非取代2 —金 剛酮化合物1當量之使用量爲1至1 〇當量，又以1至5 當量爲佳。鎂化合物超過1 0當量時，將不利於經濟面且 無意義。 稀土類鹵化物可爲氯化鑭，氯化姉，氯化鐯，氯化銨 ，氯化鉅，氯化釤，氯化銪，氯化釔，氯化铽，氯化鏑， 氯化鈥，氯化餌，氯化錶，氯化鏡，氯化鐫及對應其之溴 化物，碘化物等單獨使用或二種以上倂用。又，可使用混 合物稀土（由原石而得精製前含大量铈或鑭之鹵化物）。 該稀土類鹵化物對鎂化合物1當量之使用量爲 0·01至50當量，又以0·1至10當量爲佳。使用 量低於0 . 0 1當量時，將無法發揮提升收穫率之效果’ 又，超過5 0當量時不利於經濟面。 本發明於存在稀土類鹵化物下，使一般式（I I )所 本紙張尺度適用中國國家標準（CNS ) Α4規格（210 Χ297公釐） (請先聞讀背面之注意事項再填寫本頁}-6-1225857 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (The third alcohol of 4 is the substitution or non-substitution of the general formula (I) in the presence of rare earth halides 2- Amantadine compounds and magnesium compounds or dialkyl groups shown by the general formula (丨 IJ) RM g X (III) [wherein R is an alkyl group having 2 to 10 carbon atoms with / 3 hydrogen; and also a tooth atom] The magnesium compound is prepared by the reaction. The magnesium compound represented by the general formula (III) is a general Grignard formula. Dialkyl magnesium compounds such as dimethyl magnesium, diethyl magnesium, di-tau magnesium, and the like. The amount of magnesium compound to 1 equivalent of substituted or unsubstituted 2-adamantone compound represented by general formula (II) is 1 to 10 equivalents, and more preferably 1 to 5 equivalents. When the magnesium compound exceeds 10 equivalents, it is disadvantageous It is economically meaningless. Rare earth halides can be lanthanum chloride, sister chloride, samarium chloride, ammonium chloride, giant chloride, samarium chloride, samarium chloride, yttrium chloride, samarium chloride, chlorine Tritium chloride, chlorinated bait, chlorinated bait, chlorinated meter, chlorinated mirror, thorium chloride and corresponding bromide, iodide It can be used singly or in combination of two or more kinds. In addition, a mixture of rare earths (halides containing a large amount of cerium or lanthanum before being refined from raw stones) can be used. The rare earth halide is used in an amount of 0.01 to 1 equivalent of the magnesium compound. 50 equivalents, and preferably from 0.1 to 10 equivalents. When the amount is less than 0.01 equivalent, the effect of improving the harvest rate will not be exerted. 'Moreover, when it exceeds 50 equivalents, it is not good for the economy. The present invention exists For rare earth halides, make the paper size of the general formula (II) applicable to the Chinese National Standard (CNS) A4 specification (210 x 297 mm) (Please read the precautions on the back before filling in this page}
1225857 A7 _;_ B7 ___ 五、發明説明（g (請先閱讀背面之注意事項再填寫本頁) 示化合物與上述鎂化合物反應之條件爲，於一般使用於格 利雅試劑之溶劑中以常壓且一 5 0 °C至1 0 0 °C，又以一 1 0 °C至室溫爲佳之溫度進行〇 , 5至1 0小時。所使用 之溶劑如，四氫呋喃，二乙基醚，1，4 一二噁烷等。 下面將以實施例具體說明本發明，但非限於此例。 實施例1 將5 0 m 1三口燒瓶減壓乾燥後，放入氯化鈽酐 1 , 9g (四氫呋喃l〇ml中7 · 5毫莫耳，對2 —金 剛酮1當量爲1 · 5當量），冰浴下再加入乙基鎂氯化物 7 · 5ml (7 _ 5毫莫耳，四氫呋喃1彡中1莫耳，對 金剛酮1當量爲1 . 5當量）攪拌1小時。其後同冰浴下 以1 0分鐘滴下溶解於四氫呋喃之2 -金剛酮1 〇 m 1 ( 所含金剛酮量爲5毫莫耳）。結束滴定2小時後，以1 0 重量％乙酸水溶液結束反應，以已烷萃取後，利用氣相色 譜分析萃取液，結果生成收穫率爲9 9%之2 -乙基金剛 烷一 2 -醇，且僅生成1%還原物。 經濟部智慧財產局員工消費合作社印製 實施例2 除了以氯化鑭1 . 8 g (四氫呋喃1 0 m 1中7 . 5 毫莫耳，對2 -金剛烷1當量爲1 . 5當量）取代氯化鈽 酐外，其他同實施例1之方法，分析生成物，結果生成收 穫迕爲8 1%之2 -乙基金剛烷—2 -醇，且還原物爲 19%。 本紙張尺度適用中國國家標準（CNS ) A4規格（210 X 297公釐） 8_ 1225857 經濟部智慧財產局員工消費合作社印製 Α7 Β7 五、發明説明（έ 比較例1 除了不使用氯化鈽外，其他同實施例1之方法，分析 生成物，結果2 -乙基金剛烷一 2 -醇之收穫率爲3 1% 產業上利用可能性 工業上利用本發明之方法可低價且有效率地由2 -金 剛酮製造具有金剛烷架構之第三醇，又，可明顯抑制此時 所生成之還原物，而飛躍式提升第三醇之收穫率。 本紙張尺度適用中國國家標準（CNS ) Α4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)1225857 A7 _; _ B7 ___ V. Description of the invention (g (please read the precautions on the back before filling out this page) The conditions for the reaction of the compounds shown above with the above magnesium compounds are as follows: at normal pressure in solvents commonly used in Grignard reagents And a temperature of 50 ° C to 100 ° C, and a temperature of 10 ° C to room temperature is preferably 0.5 to 10 hours. The solvents used are, for example, tetrahydrofuran, diethyl ether, 1, 4 Dioxane, etc. The present invention will be described in detail in the following examples, but it is not limited to this example. Example 1 A 50 m 1 three-necked flask was dried under reduced pressure, and 1,9 g (tetrahydrofuran 1) was added. 7.5 millimoles in 〇ml, 1 equivalent of 2-adamantanone (1.5 equivalents), and then add ethyl magnesium chloride 7.5ml (7 _5 millimoles, tetrahydrofuran in 1 彡) in an ice bath. Moore, 1 equivalent of 1.5 mg of amantadone) was stirred for 1 hour. Then, 2-amantadine dissolved in tetrahydrofuran 10 m 1 (with an amount of 5 mmol of amantadone) was dripped in an ice bath for 10 minutes. Mol). After 2 hours from the end of the titration, the reaction was terminated with a 10% by weight aqueous acetic acid solution. After extraction with hexane, it was analyzed by gas chromatography. Taking the liquid, the result was 2-ethyladamantane-2-ol with a yield of 99%, and only 1% of the reduced product was produced. Example 2 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy 8 g (7.5 millimoles in 10 m 1 of tetrahydrofuran, 1.5 equivalents for 2-adamantane), except that the chloroanhydride was replaced, the product was analyzed in the same manner as in Example 1, and the results were obtained. The yield is 8 1% of 2-ethyladamantane-2-ol, and the reduction is 19%. This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 8_ 1225857 Wisdom of the Ministry of Economic Affairs Printed by the Consumer Affairs Cooperative of the Property Bureau A7 B7 V. Description of the invention (Comparative Example 1 Except that thallium chloride was not used, the product was analyzed in the same manner as in Example 1, and the result was 2-ethyladamantane-2-ol. Yield: 31% Industrial utilization possibility The method of the present invention can be used industrially to produce a third alcohol having an adamantane structure from 2-adamantanone at a low cost and efficiency, and it can significantly suppress the production of the third alcohol at this time. Reduction, and leap-forward increase in the yield of tertiary alcohol. Chinese National Standard (CNS) Α4 size (210X297 mm) (Please read the back of the precautions to fill out this page)
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