200300409 玖、發明說明 (發明說明應敘明.發明所屬之技術領域、先前技術、內容、嘗施方式及圖式簡 單說明） — 發明所屬之技術領域_ •本發明是有關於一種香葉草基芳基楓（geranyl arylsulfone)的製造方法，其係作爲維他命a衍生物或多種 萜烯（tapene)化合物的原料，該些維他命a衍生物及萜烯 化合物係作爲藥品、飼料添加劑或食品添加劑等等。 先前技術 本發明之發明人在前案（日本專利申請案早期公開公 報第2〇01-213860號）中揭露一種香葉草基芳基楓的製備方 法，其係在水溶液中，將價格低於芳基亞磺酸鹽的芳基磺 醯氯還原成芳基亞磺酸鹽，並在不分離的情形下於反應混 合液中加入下式（3)所示之鹵化丙烯基化合物（allylhalide compound)，而得下式（4)所示之香葉草基芳基楓。在此方 法中’進行芳基磺醯氯還原反應時的水溶液，係繼續使用 到其後加入鹵化丙烯基化合物(3)所進行之反應中，而得香 葉草基芳基楓(4)。然而，由工業生產及經濟性的觀點來看， 其產率仍有提高之必要。 發明內容 爲提高反應的產率，發明人於深入硏究後發現，在藉. 助相轉移觸媒（phase transfer catalyst)之作用而與無機鹽類 共存的情形下，芳基亞磺酸鹽與鹵化丙烯基化合物反應的 產率就可提高，其即本發明。 200300409 本發明提出 1. 一種香葉草基芳基楓的製造方法，係使用下式（3)所示之 鹵化丙烯基化合物與式（2)所示之芳基磺酸鹽，在相轉移 觸媒與無機鹽類共存之情形下進行反應，而得下式（4)所 示之香葉草基芳基楓。 (3)200300409 发明, description of the invention (the description of the invention should be stated. The technical field to which the invention belongs, the prior art, the content, the mode of application, and the drawings are briefly explained) — the technical field to which the invention belongs_ • The present invention relates to a gerbera-based A method for producing geranyl arylsulfone, which is used as a raw material of vitamin a derivatives or various kinds of tapene compounds, and these vitamin a derivatives and terpene compounds are used as medicines, feed additives or food additives, etc. . In the prior art, the inventor of the present invention disclosed in a previous case (Japanese Patent Application Laid-Open Gazette No. 2001-213860) a method for preparing geranyl-based aryl maple in an aqueous solution at a price lower than The arylsulfonyl chloride of the arylsulfinate is reduced to an arylsulfinate, and a halogenated propylene compound (allylhalide compound) represented by the following formula (3) is added to the reaction mixture without separation. Thus, geranyl aryl maple represented by the following formula (4) is obtained. In this method, the aqueous solution at the time of performing the arylsulfonyl chloride reduction reaction is continued to be used in the subsequent reaction by adding the halogenated propenyl compound (3) to obtain geranyl aryl maple (4). However, from the viewpoint of industrial production and economics, it is still necessary to increase the yield. SUMMARY OF THE INVENTION In order to improve the yield of the reaction, the inventors found that after in-depth research, in the case of coexistence with inorganic salts by the role of phase transfer catalyst, arylsulfinate and The yield of the halogenated propylene-based compound reaction can be increased, which is the present invention. 200300409 The present invention proposes a method for producing geranyl-based aryl maple, which uses a halogenated propenyl compound represented by the following formula (3) and an aryl sulfonate represented by the formula (2) in a phase transfer reaction. The reaction is carried out in the presence of a vehicle and an inorganic salt to obtain a geranyl aryl maple represented by the following formula (4). (3)
(式中X爲鹵素原子，且波狀線表示E或Z型態之幾何 異構物或其混合物）(Where X is a halogen atom, and the wavy line represents the geometric isomer of the E or Z form or a mixture thereof)
ArS02M (2) (式中Ar爲取代或未取代的芳香基，且Μ爲鈉或鉀) (4) (式中Ar及波狀線之定義同上） 2.—種香葉草基芳基楓的製造方法，係使用式（3)所示之鹵 化丙烯基化合物與式（2)所示之芳基磺酸鹽，在 a) 由碘化四級銨鹽、碘化四級鐵鹽或碘化锍鍚鹽中所選 出的相轉移觸媒，以及無機鹽，或是 b) 由氯化、溴化或硫酸氫化四級銨鹽，氯化、溴化或硫 酸氫化四級錢鹽，或是氯化、溴化或硫酸氫化毓鐺鹽 中所選出的相轉移觸媒，以及無機鹽 共存之情形下進行反應，而得上式（4)所示之香葉草基芳 8 200300409 基碉。 3.如同上述第1及2項所述之製備式（4)所示之香葉草基芳 基楓的製造方法，其中式（2)所示之芳基亞磺酸鹽係由下 式U)所示之芳基磺醯氯還原而得。ArS02M (2) (where Ar is a substituted or unsubstituted aromatic group, and M is sodium or potassium) (4) (the definition of Ar and wavy lines is the same as above) 2.—Gerberyl aryl maple The production method is based on the use of a halogenated propenyl compound represented by the formula (3) and an aryl sulfonate represented by the formula (2). In a), quaternary ammonium iodide, quaternary iron iodide or iodine The phase transfer catalyst selected from the phosphonium salts, and inorganic salts, or b) quaternary ammonium salts from chlorinated, brominated or sulfated quaternary salts, The selected phase transfer catalyst in the chlorinated, brominated or hydrogenated sulphuric acid salt and the inorganic salt coexist, and the reaction is performed to obtain geranyl 8 8 00 00409 based on the formula (4). 3. The method for producing geranyl aryl maple represented by formula (4) as described in items 1 and 2 above, wherein the arylsulfinate represented by formula (2) is represented by the following formula U ) Is obtained by reduction of arylsulfonium chloride.
ArS〇2Cl (1) (式中Ar定義與式（2)相同） 爲讓本發明之上述和其他目的、特微、和優點能更明 顯易懂，下文特舉較佳實施例作詳細說明如下。 實施方式 以下將詳細說明本發明。 在本發明中，式（1)、（2)及（4)所示之化合物中的取代 基Ar表示有取代或未取代的芳香基，此芳香基例如是苯 基或萘基等。芳香基上的取代基例如是Ci〜C5的直鏈或具 支鏈烷基（如甲基、乙基、正丙基、異丙基、正丁基、三 級丁基、正戊基等）、的直鏈或具支鏈烷氧基（如甲 氧基、乙氧基、正丙氧基、異丙氧基、正丁氧基、三級丁 氧基、正戊氧基、三級戊氧基、新戊氧基等）、鹵素原子， 以及硝基等等。取代基Ar之具體實例包括：苯基、萘基、 鄰甲苯基、間甲苯基、對甲苯基、鄰甲氧苯基、間甲氧苯 基、對甲氧苯基、鄰氯苯基、間氯苯基、對氯苯基、鄰溴 苯基、間溴苯基、對溴苯基、鄰碘苯基、間碘苯基、對碘 苯基、鄰氟苯基、間氟苯基、對氟苯基、鄰硝基苯基、間 硝基苯基及對硝基苯基等等。ArS〇2Cl (1) (In the formula, the definition of Ar is the same as in formula (2).) In order to make the above and other objects, features, and advantages of the present invention more comprehensible, the preferred embodiments are described in detail below as follows. . Embodiments The present invention will be described in detail below. In the present invention, the substituent Ar in the compounds represented by the formulae (1), (2) and (4) represents a substituted or unsubstituted aromatic group, and the aromatic group is, for example, a phenyl group or a naphthyl group. The substituent on the aromatic group is, for example, a linear or branched alkyl group of Ci ~ C5 (such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tertiary butyl, n-pentyl, etc.) , Linear or branched alkoxy (such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tertiary butoxy, n-pentyloxy, tertiary pentyl Oxygen, neopentyloxy, etc.), halogen atoms, and nitro and so on. Specific examples of the substituent Ar include: phenyl, naphthyl, o-tolyl, m-tolyl, p-tolyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-chlorophenyl, m Chlorophenyl, p-chlorophenyl, o-bromophenyl, m-bromophenyl, p-bromophenyl, o-iodophenyl, m-iodophenyl, p-iodophenyl, o-fluorophenyl, m-fluorophenyl, p Fluorophenyl, o-nitrophenyl, m-nitrophenyl and p-nitrophenyl, etc.
另外，式（3)所示之鹵化丙烯基化合物上的取代基X 200300409 表示鹵素原子，其具體實例爲氯原子、溴原子及碘原子。 本發明所用之芳基亞磺酸鹽例如可由式（1)所示之芳基 磺醯氯還原而得，此還原反應較佳在還原劑及驗存在的情 形下，於水溶液中進行。所用之還原劑較佳爲亞硫酸鹽或 亞硫酸氫鹽，其具體實例包括亞硫酸鈉、亞硫酸鉀、亞硫 酸氫鈉及亞硫酸氫鉀等，且其用量一般爲芳基磺醯氯（1)莫 耳數的1〜2.5倍，且較佳爲1.02〜2.00倍。 上述還原反應如在偏酸性之環境下進行，則自由狀態 之亞磺酸會產生自身氧化還原反應而生成副產物硫代磺酸 根（thiosulfonate)，致使產率降低。爲避免此情形，此反應 較佳在與鹼共存，且pH値達8以上的鹼性條件下進行。 此共存之鹼類較佳爲鹼金族金屬的氫氧化物、鹼金族金屬 的碳酸鹽及鹼金族金屬的碳酸氫鹽等，其具體實例爲氫氧 化鈉、氫氧化鉀、碳酸鈉、碳酸鉀、碳酸氫鈉及碳酸氫鉀 等，且使用量一般爲芳基磺醯氯（1)莫耳數的1〜5倍，而較 佳爲1·02〜2.50倍。反應溫度一般爲0°C〜100。(：，且較佳 爲2〇QC〜70QC。另外，反應時間介於1至24小時之間。 在反應結束後，可以濃縮等方法分離產物，但亦可不 進行此後續處理，而直接在所得之水溶液的反應混合物中 加入式（3)所示之鹵化丙烯基化合物以進行反應，而得式（4) 所示之香葉草基芳基楓。其中，所加入之鹵化丙烯基化合 物（3)的使用量一般爲芳基磺醯氯（1)莫耳數的〇·3〜1·2倍， 而較佳爲0.7〜1倍。 另外，上述反應較佳在與相轉移觸媒及無機鹽類共存 200300409 之情形下，於水/疏水性有機溶劑所構成的兩相系統中進 行。 在使用兩相系統進行反應時，疏水性有機溶劑例如可 爲正己烷、正庚烷、環己烷、苯、甲苯、二甲苯等烴類溶 劑；N氯丁烷、1，2-二氯乙烷、氯苯、鄰二氯苯、三氟甲 基苯等鹵化物類溶劑；甲基異丁基酮、甲乙酮、乙酸甲酯、 乙酸乙酯等羰類溶劑；以及乙醚、環戊基甲基醚、甲基三 級丁基醚等醚類溶劑等等。 另外，相轉移觸媒例如爲四級銨鹽、四級鐵鹽及锍鐺 鹽等等。四級銨鹽例如爲氯化四甲基銨、氯化四乙基銨、 氯化四丙基銨、氯化四丁基銨、氯化四戊基銨、氯化四己 基銨、氯化四庚基銨、氯化四辛基銨、氯化三辛基甲基銨、 氯化四癸基銨、氯化三癸基甲基銨、氯化二癸基二甲基銨、 氯化四（十二烷基）銨、氯化三（十二烷基）甲基銨、氯化二（十 二烷基）二甲基銨、氯化十二烷基三甲基銨、氯化十二烷 基三乙基銨、氯化十四烷基三甲基銨、氯化四（十六烷基） 銨、氯化十六烷基三甲基銨、氯化十六烷基二甲基乙基銨、 氯化四（十八烷基）銨、氯化十八烷基三甲基銨、氯化十八 烷基三乙基銨、氯化苯甲基三甲基銨、氯化苯甲基三乙基 銨、氯化苯甲基三丁基銨、氯化1-甲基吡啶鐺(pyridinium)、 氯化1-十六烷基吡啶鐺、氯化Μ-二甲基吡啶鍚及氯化三 甲基環丙基銨等，或是與該些氯鹽對應之溴鹽、碘鹽或硫 酸氫鹽等化合物。 四級鱗鹽例如爲氯化三丁基甲基辚、氯化三乙基甲基 200300409 錢、氯化甲基三苯氧基鐵、氯化丁基三苯基錢、氯化四丁 基鱗、氯化苯甲基三苯基鱗、氯化四辛基鍈、氯化十六烷 基三甲基鱗、氯化十六院基三丁基鱗、氯化十六院基二甲 基乙基鱗及氯化四苯基錢等，或是與該些氯鹽對應之溴 鹽、碘鹽或硫酸氫鹽等化合物。 上述之锍鐵鹽例如爲氯化苯甲基甲基乙基锍鐺、氯化 苯甲基二甲基毓鎰、氯化苯甲基二乙基锍鍚、氯化二丁基 甲基锍鐺、氯化三甲基锍鐺、氯化三乙基锍鐺及氯化三丁 基锍鎰等，或是與該些氯鹽對應之溴鹽、碘鹽或硫酸氫鹽 等化合物。 這些相轉移觸媒中較佳者爲碘化物觸媒，尤其是碘化 四級銨鹽。如所用者爲硫酸氫鹽、氯鹽或溴鹽，則反應較 佳在碘化鈉或碘化鉀等鹼金族金屬碘化物共存的條件下進 行。 另外，相轉移觸媒之使用量爲鹵化丙烯基化合物（3)莫 耳數的0.001〜0.2倍，且較佳爲0.01〜0.1倍。 在本發明中，無機鹽類之添加可以有效地減少相轉移 觸媒的使用量，尤其是高價的碘化四級銨鹽的使用量，並 可提高反應性。 此無機鹽類例如爲鹼金族金屬或鹼土族金屬的氯鹽或 溴鹽，其具體實例爲氯化鈉、氯化鉀、溴化鈉、溴化鉀、 氯化鈣、溴化鈣、氯化鎂及溴化鎂等。此無機鹽類之使用 量依前一程序的水溶液量而定，當前一程序（芳基磺醯氯 的還原反應）僅使用不會影響到攪拌效率及反應產率等方 12 200300409 面的最少水量時’其用量可爲鹵化丙烯基化合物（3)的 20〜300wt% ’ 且較佳爲 5〇〜2〇〇wt〇/〇。 此外’反應溫度一般爲30。(3〜110。(：，較佳爲50qC 〜l〇〇°C。另反應時間介於丨至％小時之間。 在反應之後，所得之香葉草基芳基楓（4)可以萃取、洗 淨、再結晶或各種層析法等加以分離純化。 發明之效果 如上所述’本發明之方法係使用便宜的芳基磺醯氯作 爲起始物’在同一反應容器中以高產率製備香葉草基芳基 楓(4)。由於本發明使用便宜的原料、且能減少相轉移觸媒 (尤其是筒價的碘化四級銨鹽）的使用量，又僅使用水爲溶 劑而得高產率之產物，所以由工業生產的觀點來看是一種 有利的方法。 以下將以數個實例詳細說明本發明，但本發明之範圍 並不僅限於該些實例所述者。 實例 (實例1) 首先將400mg (2.1 mmol)的對甲苯磺醯氯、300mg (2.3 mmol)的亞硫酸鈉及244mg (2.3 mmol)的碳酸鈉懸浮在2ml 的水中，再於50°C下攪拌2小時。接著，在上述反應混 合物中加入14.8mg (0.04 mmol，2 mol%)的碘化四丁基錢 及345mg的氯化鈉，再加入361mg (2.0 mmol)純度95.5% 的氯化香葉嫌（gerany1 chl〇ride)，並於96°C下攪拌4小時υ 在反應結束後’於反應溶液中加入少量水’再以甲苯萃取 13 200300409 香葉草基對甲苯基楓（geranyl-p-tolylsulfone)，並以氣相層 析儀分析得知其產率爲92% (以氯化香葉烯用量爲準）。 (比較例1) 此例進行反應之條件大致與實例1相同，除了未加入 氯化鈉之外。由氣相層析儀分析得知香葉草基對甲苯基楓 的產率爲78% (以氯化香葉烯用量爲準）。 (實例2〜4) 此例進行反應之條件大致與實例1相同，除了氯化鈉 的用量改成690mg，且碘化四丁基銨的用量改變成下表所 示者之外。接著以氣相層析儀進行分析，所得之香葉草基 對甲苯基楓的產率如下表所示： 表1 實例 2 3 4 碘化四丁基 錢的添加量 7.4mg (0.02mmol， 1 mol%) 22.2mg (0.06mmol， 3mol%) 2 9.5 m g (0.08mmol, 4mol%) 座牟 81% 97% 98% (實例5)The substituent X 200300409 on the halogenated propenyl compound represented by the formula (3) represents a halogen atom, and specific examples thereof include a chlorine atom, a bromine atom, and an iodine atom. The arylsulfinate used in the present invention can be obtained, for example, by reduction of an arylsulfonium chloride represented by the formula (1), and the reduction reaction is preferably carried out in an aqueous solution in the presence of a reducing agent and the presence thereof. The reducing agent used is preferably a sulfite or bisulfite, and specific examples thereof include sodium sulfite, potassium sulfite, sodium bisulfite, potassium bisulfite, etc., and the amount thereof is generally arylsulfonyl chloride (1) Molar number is 1 to 2.5 times, and preferably 1.02 to 2.00 times. If the above reduction reaction is performed in a slightly acidic environment, the free state sulfinic acid will generate an auto-reduction reaction to generate a by-product thiosulfonate, resulting in a decrease in yield. To avoid this, the reaction is preferably carried out under alkaline conditions in which coexistence with a base and a pH of 8 or higher. The coexisting bases are preferably hydroxides of alkali metals, carbonates of alkali metals, bicarbonates of alkali metals, and the like. Specific examples are sodium hydroxide, potassium hydroxide, sodium carbonate, Potassium carbonate, sodium bicarbonate, potassium bicarbonate, etc., and the amount used is generally 1 to 5 times the molar number of arylsulfonyl chloride (1), and preferably 1.02 to 2.50 times. The reaction temperature is generally 0 ° C ~ 100. (:, And preferably 20QC ~ 70QC. In addition, the reaction time is between 1 and 24 hours. After the reaction is completed, the product can be isolated by concentration and other methods, but the subsequent treatment may not be performed, but directly obtained A halogenated propylene-based compound represented by the formula (3) is added to the reaction mixture of an aqueous solution to perform a reaction, thereby obtaining a geranyl aryl maple represented by the formula (4). Among them, the halogenated propylene-based compound (3 ) Is generally used in an amount of 0.3 to 1.2 times the molar number of arylsulfonyl chloride (1), and preferably 0.7 to 1 times. In addition, the above reaction is preferably performed with a phase transfer catalyst and inorganic In the case of coexistence of salts 200300409, the reaction is performed in a two-phase system composed of water / hydrophobic organic solvent. When a two-phase system is used for the reaction, the hydrophobic organic solvent may be, for example, n-hexane, n-heptane, or cyclohexane. , Benzene, toluene, xylene and other hydrocarbon solvents; N-chlorobutane, 1,2-dichloroethane, chlorobenzene, o-dichlorobenzene, trifluoromethylbenzene and other halide solvents; methyl isobutyl Ketones, methyl ethyl ketone, methyl acetate, ethyl acetate and other carbonyl solvents; and ether, Ether solvents such as amyl methyl ether, methyl tertiary butyl ether, etc. In addition, the phase transfer catalyst is, for example, a quaternary ammonium salt, a quaternary iron salt, a tin salt, etc. The quaternary ammonium salt is, for example, Tetramethylammonium chloride, tetraethylammonium chloride, tetrapropylammonium chloride, tetrabutylammonium chloride, tetrapentylammonium chloride, tetrahexylammonium chloride, tetraheptylammonium chloride, chloride Tetraoctylammonium, trioctylmethylammonium chloride, tetradecylammonium chloride, tridecylmethylammonium chloride, didecyldimethylammonium chloride, tetradecylammonium chloride , Tris (dodecyl) methylammonium chloride, bis (dodecyl) dimethylammonium chloride, dodecyltrimethylammonium chloride, dodecyltriethylammonium chloride, Tetradecyltrimethylammonium chloride, tetrakis (hexadecyl) ammonium chloride, cetyltrimethylammonium chloride, cetyldimethylethylammonium chloride, tetrakis ( Octadecyl) ammonium, stearyltrimethylammonium chloride, stearyltriethylammonium chloride, benzyltrimethylammonium chloride, benzyltriethylammonium chloride, chloride Benzyltributylammonium, 1-methylpyridinium chloride, 1-hexadecylpyridine, M-dimethylpyridine chloride, trimethylcyclopropylammonium chloride, etc., or bromine, iodide or hydrogen sulfate corresponding to these chloride salts Examples of quaternary scale salts are tributylmethylphosphonium chloride, triethylmethyl chloride 200 300 409, methyl chloride triphenoxy iron, butyl triphenyl chloride, tetrabutyl chloride , Benzyltriphenyl chloride scale, tetraoctylphosphonium chloride, cetyltrimethyl chloride scale, cetyl chloride tributyl scale, cetyl chloride dimethyl ethyl Basic scale, tetraphenyl chloride, etc., or bromide, iodide, or hydrogen sulfate corresponding to these chloride salts. Examples of the above-mentioned osmium iron salts are benzylmethyl ethyl chlorochloride , Benzyl dimethyl chloride, benzyl diethyl chloride, dibutyl methyl chloride, trimethyl chloride, triethyl chloride, and trichloride Butylphosphonium and the like, or bromine, iodide, or hydrogen sulfate corresponding to these chloride salts. Preferred among these phase transfer catalysts are iodide catalysts, especially quaternary ammonium iodide salts. If the bisulfate, chloride or bromine salt is used, the reaction is preferably carried out under conditions in which alkali metal iodides such as sodium iodide or potassium iodide coexist. In addition, the amount of the phase transfer catalyst used is 0.001 to 0.2 times the mole number of the halogenated propylene-based compound (3), and preferably 0.01 to 0.1 times. In the present invention, the addition of inorganic salts can effectively reduce the amount of phase transfer catalyst used, especially the amount of expensive quaternary ammonium iodide salt, and can improve the reactivity. The inorganic salts are, for example, chloride salts or bromine salts of alkali metal or alkaline earth metals, and specific examples thereof are sodium chloride, potassium chloride, sodium bromide, potassium bromide, calcium chloride, calcium bromide, magnesium chloride And magnesium bromide. The amount of this inorganic salt used depends on the amount of aqueous solution in the previous procedure. In the current procedure (reduction reaction of arylsulfonyl chloride), only the minimum amount of water will be used without affecting stirring efficiency and reaction yield. The amount thereof may be 20 to 300% by weight of the halogenated propylene-based compound (3), and preferably 50 to 200% by weight. The reaction temperature is generally 30. (3 ~ 110. (:, Preferably 50qC ~ 100 ° C. In addition, the reaction time is between 丨 and% hours. After the reaction, the obtained geranyl aryl maple (4) can be extracted, Wash, recrystallize, and separate and purify by various chromatographic methods, etc. Effect of the Invention As described above, the "method of the present invention uses inexpensive arylsulfonyl chloride as a starting material" in the same reaction vessel to produce fragrant in a high yield. Leaf grass-based aryl maple (4). Because the present invention uses cheap raw materials and can reduce the amount of phase transfer catalyst (especially the quaternary quaternary ammonium iodide salt), it is obtained by using only water as a solvent. High-yield product, so it is an advantageous method from the viewpoint of industrial production. The present invention will be described in detail with several examples below, but the scope of the present invention is not limited to those described by these examples. Examples (Example 1) First, 400 mg (2.1 mmol) of p-toluenesulfonyl chloride, 300 mg (2.3 mmol) of sodium sulfite and 244 mg (2.3 mmol) of sodium carbonate were suspended in 2 ml of water, and then stirred at 50 ° C. for 2 hours. Then, as above To the reaction mixture was added 14.8 mg (0.04 mmol, 2 mol%) of Tetrabutyl iodide and 345 mg of sodium chloride, 361 mg (2.0 mmol) of 95.5% pure geranyl chloride (gerany1 chl〇ride) was added, and stirred at 96 ° C for 4 hours. 'Add a small amount of water to the reaction solution' and extract with toluene13 200300409 Geranyl-p-tolylsulfone and analyze by gas chromatography to find that the yield is 92% (using chlorine (Comparative Example 1) (Comparative Example 1) The reaction conditions in this example were roughly the same as in Example 1, except that sodium chloride was not added. Analysis by gas chromatography revealed that geranyl p-tolyl group The yield of maple is 78% (based on the amount of geranyl chloride). (Examples 2 to 4) The reaction conditions in this example are roughly the same as in Example 1, except that the amount of sodium chloride is changed to 690 mg and iodinated. The amount of tetrabutylammonium was changed to something other than those shown in the table below. Then the gas chromatograph was used to analyze the yield of the obtained geranyl p-tolyl maple as shown in the following table: Table 1 Example 2 3 4 Addition of tetrabutyl iodide 7.4mg (0.02mmol, 1 mol%) 22.2mg (0.06mmol, 3mol%) 2 9.5 mg (0.08mmol, 4mol% ) Block 81% 97% 98% (Example 5)
首先將400mg (2.1 mmol)的對甲苯磺醯氯、300mg (2.3 mmol)的亞硫酸鈉及244mg (2.3 mmol)的碳酸鈉懸浮在2ml 的水中，再於50°C下攪拌2小時。接著，在上述反應混 合物中加入12.9mg (0.04mmol，2mol%)的溴化四丁基錢、 15mg (O.lmmol，5mol%)的碘化鈉及690mg的氯化鈉，再 加入361 mg (2.0 mmol)純度95.5%的氯化香葉烯，並於96°C 14 200300409 下攪拌3小時。在反應結束後，於反應溶液中加入少量水， 再以甲苯萃取香葉草基對甲苯棊楓，並以氣相層析儀分析 得知其產率爲93% (以氯化香葉烯用量爲準）。 (實例6) 此例進行反應之條件大致輿實例5相同’除了溴化四 丁基銨的用量改成32.2mg (O.lrnmol，5mol%)之外。以氣相 層析儀分析得知香葉草基對甲苯基楓的產率爲96% (以氯 化香葉烯用量爲準）。 (比較例2) 此例進行反應之條件大致與實例6相同，除了未加入 氯化鈉之外。由氣相層析儀分析得知香葉草基對甲苯基楓 •的產率爲86% (以氯化香葉烯用量爲準）。 (實例7) 此例進行反應之條件大致與實例5相同，除了以 13.6mg (0.04mmol，2mol%)的硫酸氫化四丁基銨取代溴化 四丁基銨之外。以氣相層析儀分析得知香葉草基對甲苯基 楓的產率爲92% (以氯化香葉烯用量爲準)。 (實例8) 首先將400mg (2.1 mmol)的對甲苯磺醯氯、300mg (2.3 mmol)的亞硫酸鈉及244mg (2.3 mmol)的碳酸鈉懸浮在2ml 的水中，再於50°C下攪拌2小時。接著，在上述反應混 合物中加入7.5mg (0.02mmol，lmol%)的碘化四丁基銨及 776mg的氯化鈉，再加入由388mg (2.0mmol)純度89%之 氯化香葉烯溶於2ml甲基異丁基酮所得之溶液，並於 15 200300409 85〜9(TC下攪拌3小時。在反應結束後，於反應溶液中加 入飽和氯化銨水溶液，再以乙酸乙酯進行萃取，然後加入 飽和食鹽水洗淨萃取液，再以無水硫酸鎂除去水分。接著 蒸餾除去溶劑，所得之油狀物再以氣相層析法進行分析， 得知香葉草基對甲苯基楓之產率爲97% (以氯化香葉烯用 量爲準）。 (比較例3) 此例進行反應之條件大致與實例8相同，除了未加入 氯化鈉之外。由氣相層析儀分析得知香葉草基對甲苯基楓 的產率爲71% (以氯化香葉烯用量爲準）。 (實例9) 首先將4〇〇mg (2.1 mmol)的對甲苯磺醯氯、3〇〇mg (2.3 mmol)的亞硫酸鈉及244mg (2.3 mmol)的碳酸鈉懸浮在2ml 的水中，再於50°C下攪拌2小時。接著，在上述反應混 合物中加入22.2mg (0.06mmol，3mol%)的碘化四丁基銨及 690mg的氯化鈉’再加入由361mg (2.0mmol)純度95.5% 之氯化香葉烯溶於2ml甲苯所得之溶液，並於96°C下攪 拌3小時。在反應結束後，於反應溶液中加入少量水，再 以甲苯進行萃取，再以氣相層析法進行分析，得知香葉草 基對甲苯基楓之產率爲91% (以氯化香葉烯用量爲準）。 雖然本發明已以較佳實施例揭露如上，然其並非用以 限定本發明，任何熟習此技藝者，在不脫離本發明之精神 和範圍內，當可作各種之更動與潤飾，因此本發明之保護 範圍當視後附之申請專利範圍所界定者爲準。 16First, 400 mg (2.1 mmol) of p-toluenesulfonyl chloride, 300 mg (2.3 mmol) of sodium sulfite and 244 mg (2.3 mmol) of sodium carbonate were suspended in 2 ml of water, and then stirred at 50 ° C. for 2 hours. Next, 12.9 mg (0.04 mmol, 2 mol%) of tetrabutyl bromide, 15 mg (0.1 mmol, 5 mol%) of sodium iodide, and 690 mg of sodium chloride were added to the above reaction mixture, and 361 mg ( 2.0 mmol) geranyl chloride with a purity of 95.5%, and stirred at 96 ° C 14 200300409 for 3 hours. After the reaction was completed, a small amount of water was added to the reaction solution, and the geranyl-p-toluene maple was extracted with toluene, and analyzed by gas chromatography. The yield was 93% (based on the amount of geranyl chloride). Prevails). (Example 6) The reaction conditions in this example were roughly the same as those in Example 5 except that the amount of tetrabutylammonium bromide was changed to 32.2 mg (0.1 mol, 5 mol%). Analysis by gas chromatography revealed that the yield of geranyl p-tolyl maple was 96% (based on the amount of chlorgeranyl). (Comparative Example 2) The reaction conditions in this example were substantially the same as in Example 6, except that sodium chloride was not added. Analysis by gas chromatography revealed that the yield of geranyl p-tolyl maple was 86% (based on the amount of geranyl chloride). (Example 7) The reaction conditions in this example were roughly the same as those in Example 5, except that tetrabutylammonium bromide was replaced with 13.6 mg (0.04 mmol, 2 mol%) of tetrabutylammonium bromide. Analysis by gas chromatography revealed that the yield of geranyl p-tolyl maple was 92% (based on the amount of geranyl chloride). (Example 8) First, 400 mg (2.1 mmol) of p-toluenesulfonyl chloride, 300 mg (2.3 mmol) of sodium sulfite and 244 mg (2.3 mmol) of sodium carbonate were suspended in 2 ml of water, and then stirred at 50 ° C. for 2 hours. Next, 7.5 mg (0.02 mmol, 1 mol%) of tetrabutylammonium iodide and 776 mg of sodium chloride were added to the above reaction mixture, and 388 mg (2.0 mmol) of geranyl chloride having a purity of 89% was added to dissolve 2 ml of the solution obtained from methyl isobutyl ketone, and stirred at 15 200300409 85 ~ 9 (TC for 3 hours. After the reaction was completed, a saturated ammonium chloride aqueous solution was added to the reaction solution, followed by extraction with ethyl acetate, and then Saturated brine was added to wash the extract, and then the water was removed with anhydrous magnesium sulfate. The solvent was then distilled off, and the obtained oil was analyzed by gas chromatography. It was found that the yield of geranyl p-tolyl maple was 97% (based on the amount of geranyl chloride). (Comparative Example 3) The reaction conditions in this example were approximately the same as in Example 8, except that sodium chloride was not added. Analysis by gas chromatography revealed that geraniol Yield of p-tolyl maple was 71% (based on the amount of geranyl chloride). (Example 9) First, 400 mg (2.1 mmol) of p-toluenesulfonyl chloride and 300 mg ( 2.3 mmol) of sodium sulfite and 244 mg (2.3 mmol) of sodium carbonate were suspended in 2 ml of water, and then at 50 ° C Stir for 2 hours. Next, add 22.2mg (0.06mmol, 3mol%) of tetrabutylammonium iodide and 690mg of sodium chloride to the above reaction mixture, and then add 361mg (2.0mmol) of 95.5% pure chloride. A solution of folene dissolved in 2 ml of toluene and stirred at 96 ° C for 3 hours. After the reaction was completed, a small amount of water was added to the reaction solution, and then extracted with toluene, and then analyzed by gas chromatography to obtain The yield of geranyl p-tolyl maple is 91% (based on the amount of geranyl chloride). Although the present invention has been disclosed in the preferred embodiment as above, it is not intended to limit the present invention. Artists can make various modifications and retouching without departing from the spirit and scope of the present invention, so the protection scope of the present invention shall be determined by the scope of the appended patent application.