TWI741001B - 製備經取代之苯乙烯衍生物的方法 - Google Patents
製備經取代之苯乙烯衍生物的方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 125000003011 styrenyl group Chemical class [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 title claims abstract 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical class C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 8
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 7
- 239000008096 xylene Substances 0.000 claims description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000011877 solvent mixture Substances 0.000 claims description 5
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 150000004703 alkoxides Chemical class 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
- 239000003849 aromatic solvent Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 2
- 239000003513 alkali Substances 0.000 claims 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 150000003440 styrenes Chemical class 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- JESXATFQYMPTNL-UHFFFAOYSA-N 2-ethenylphenol Chemical compound OC1=CC=CC=C1C=C JESXATFQYMPTNL-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- -1 2-methyl-THF Chemical compound 0.000 description 5
- ITIROJLQLPHMEQ-UHFFFAOYSA-N 3-chloro-2-ethenylphenol Chemical compound OC1=CC=CC(Cl)=C1C=C ITIROJLQLPHMEQ-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- WBXNEWSPJGDBNS-UHFFFAOYSA-N 1,5,5-trichloro-6-ethenyl-7-oxabicyclo[4.1.0]heptane Chemical compound C1CCC(Cl)(Cl)C2(C=C)OC21Cl WBXNEWSPJGDBNS-UHFFFAOYSA-N 0.000 description 2
- MCBGBITUMUAJMT-UHFFFAOYSA-N 2-ethenyl-3-methylphenol Chemical compound CC1=CC=CC(O)=C1C=C MCBGBITUMUAJMT-UHFFFAOYSA-N 0.000 description 2
- OHAQUYYKIRRFOT-UHFFFAOYSA-N 3-bromo-2-ethenylphenol Chemical compound OC1=CC=CC(Br)=C1C=C OHAQUYYKIRRFOT-UHFFFAOYSA-N 0.000 description 2
- POFDVCDWYTWQRK-UHFFFAOYSA-N CS(=O)(=O)OC1=C(C(=CC=C1)Br)C=C Chemical compound CS(=O)(=O)OC1=C(C(=CC=C1)Br)C=C POFDVCDWYTWQRK-UHFFFAOYSA-N 0.000 description 2
- LXBQZZUUVNOYHV-UHFFFAOYSA-N CS(=O)(=O)OC1=C(C(=CC=C1)C)C=C Chemical compound CS(=O)(=O)OC1=C(C(=CC=C1)C)C=C LXBQZZUUVNOYHV-UHFFFAOYSA-N 0.000 description 2
- KHKROLXZCBSKRR-UHFFFAOYSA-N CS(=O)(=O)Oc1cccc(Cl)c1C=C Chemical compound CS(=O)(=O)Oc1cccc(Cl)c1C=C KHKROLXZCBSKRR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 0 *c1c(C=C)c(O)ccc1 Chemical compound *c1c(C=C)c(O)ccc1 0.000 description 1
- NLPBTJNIFVSZLK-UHFFFAOYSA-N 4-chloro-2,3-dihydro-1-benzofuran Chemical compound ClC1=CC=CC2=C1CCO2 NLPBTJNIFVSZLK-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012868 active agrochemical ingredient Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
- A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/28—Alcohols containing only six-membered aromatic rings as cyclic part with unsaturation outside the aromatic rings
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/06—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by conversion of non-aromatic six-membered rings or of such rings formed in situ into aromatic six-membered rings, e.g. by dehydrogenation
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- C07—ORGANIC CHEMISTRY
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/88—Use of additives, e.g. for stabilisation
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- C07C39/18—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with unsaturation outside the aromatic ring
- C07C39/19—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with unsaturation outside the aromatic ring containing carbon-to-carbon double bonds but no carbon-to-carbon triple bonds
- C07C39/20—Hydroxy-styrenes
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- C07C39/24—Halogenated derivatives
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Abstract
本發明係關於製備經取代之苯乙烯衍生物的方法。
Description
本發明關於製備經取代之苯乙烯衍生物的方法。
已知經取代之苯乙烯衍生物為製備活性農用化學品成分之有用中間體(見WO 2012/025557之實施例)。
文獻中記載製備此種經取代之苯乙烯衍生物的多種方法。
一可製備3-氯-2-乙烯苯酚的方法係記載於WO 2015/189114與US5424460。該製備係藉由在鹼性條件下2,2,6-三氯-1-乙烯基-7-氧雜雙環[4.1.0]庚烷之芳化來進行。此方法的缺點為使用有機金屬試劑製備2,2,6-三氯-1-乙烯基-7-氧雜雙環[4.1.0]庚烷，並且此種前驅物傾向於在製備過成形成寡聚物或聚合物。
製備2-乙烯苯酚的替代方案與一般可能性由鹼性條件下之2,3-二氫苯并呋喃的開環所構成。例如，在HMPA或DMSO、於20至60℃之溫度與5小時之反應時間，以2.3當量的LiNH2作為鹼處理2,3-二氫苯并呋喃，提供了產率95%之2-乙烯苯酚(Doklady Akademii Nauk SSSR 1978, 239,1357)。此方法的缺點為使用LiNH2為非常強的鹼，及使用HMPA或DMSO為溶劑，因為此等物質非常不適合用於工業使用。在二乙醚、於35℃之溫度與四十五小時之反應時間，以1.5當量之LiNEt2作為鹼處理2,3-二氫
苯并呋喃，提供產率25%之2-乙烯苯酚(Chem.Ber. 1960, 93,1496)。此方法的缺點為使用LiNEt2為非常強的鹼，及使用二乙醚為溶劑，因為此等物質非常不適合用於工業使用。再者，藉由所述方法達成2-乙烯苯酚之25%的低產率，並且需要非常長的反應時間。基於此等理由，該方法係不適合用於工業使用。
由於經取代之苯乙烯衍生物作為合成新穎活性農用化學品成分單位之重要性，所著眼的問題為找出可用於工業規模且不昂貴並且避免上述缺點的方法。亦期望獲得具高產率與高純度的特定苯乙烯衍生物，使得目標化合物較佳為不需要接受任何進一步潛在複雜的純化。
此目標係藉由如下方法達成：一種製備式(I)之經取代之苯乙烯衍生物的方法：
其中R1 為Cl(Ia)、Br(Ib)或甲基(Ic)，其特徵在於：式(II)之二氫苯并呋喃衍生物
其中R1 為Cl、Br或甲基係在烷氧化物或氫氧化物鹼的存在下藉由加熱反應，以獲得式(I)之化合物。
較佳者為根據本發明之方法，其中式(I)與(II)之基團的定義如下：R1 為Cl。
方法之敘述
根據本發明之反應係如流程圖1所示。
藉由根據本發明之方法所獲得之期望的通式(I)之苯乙烯衍生物具有良好的產率與高純度。
根據本發明之方法具有優於上述方法的優點，即起始材料能夠以工業規模製備，且出乎意料地該方法可藉由使用較弱的鹼如氫氧化鉀成功地進行。
根據本發明之方法有用的溶劑原則上包括在反應條件下為惰性的任何有機溶劑或溶劑混合物，包括：醚類(諸如：1,2-二甲氧基乙烷(DME)、二甘二甲醚、四氫呋喃(THF)、2-甲基-THF、苯甲醚與1,4-二噁烷)；醯胺溶劑類(諸如：DMF、N,N-二甲基乙醯胺(DMAc))與偶極非質子溶劑類(諸如：DMSO)。較佳者為使用THF、2-甲基-THF、二噁烷、DME、苯甲醚、二甘二甲醚、DMF、或DMAc、或DMAc與醚類之混合物、或DMAc 與芳族溶劑類(諸如：甲苯、二甲苯、氯苯或1,2-二氯苯)之混合物。尤佳者為使用DMAc、DMF、或二甘二甲醚、或DMAc或DMF與THF之混合物、2-甲基-THF、二噁烷、DME、甲苯、二甲苯、氯苯或1,2-二氯苯。
根據本發明之方法有用的烷氧化物鹼之實例包含下列者：tert-丁氧化鉀、tert-丁氧化鈉、甲氧化鈉、乙氧化鈉或甲氧化鉀。根據本發明之方法有用的氫氧化物鹼之實例包含下列者：氫氧化鉀。較佳者為使用氫氧化鉀、tert-丁氧化鉀、tert-丁氧化鈉或甲氧化鈉。尤佳者為使用氫氧化鉀或tert-丁氧化鉀。
尤佳為溶劑與上述鹼之群組的下列組合：
a)二甘二甲醚與氫氧化鉀之組合
b)DMAc與氫氧化鉀之組合
c)DMF與氫氧化鉀之組合
d)DMAc與甲苯、二甲苯、氯苯、1,2-二氯苯、二噁烷、DME、2-甲基-THF或THF之溶劑混合物及氫氧化鉀之組合
e)DMF與甲苯、二甲苯、氯苯、1,2-二氯苯、二噁烷、DME、2-甲基-THF或THF之溶劑混合物及氫氧化鉀之組合
f)DMAc、DMF、THF、2-甲基-THF、二噁烷、DME、苯甲醚或二甘二甲醚或此等溶劑之混合物與tert-丁氧化鉀之組合。
根據本發明之方法尤佳為溶劑與鹼之下列組合：DMAc或二甘二甲醚與氫氧化鉀。
根據本發明之方法之溫度可在很寬的範圍內變化。習慣上之操作溫度為自20℃至120℃。反應較佳為在80℃至120℃範圍之溫度進行。反應尤佳為在100℃至120℃範圍之溫度進行。
根據本發明之方法通常係在標準壓力下進行。亦可在減壓或升壓(正壓)下進行反應。
式(II)之化合物對上述群組的鹼之莫耳比可在很寬的範圍 內變化。典型地，係採用1：1至1：5之莫耳比。對有機鹼如tert-丁氧化鉀而言，較佳為1：1至1：1.5之莫耳比。尤佳者為1：1.1之莫耳比.對無機鹼如氫氧化鉀而言，較佳為1：2至1：4之莫耳比。尤佳者為1：3之莫耳比。
反應時間短，且在約0.5至約5小時之範圍。可為較長反應時間，但在經濟上不值得。
式(I)之化合物未被分離。式(I)之化合物係直接(當使用tert-丁氧化鉀作為鹼時)或在中間體後處理後(當使用氫氧化鉀作為鹼時)進一步與式(III)之化合物反應(流程圖2)。獲得式(III)化合物之反應係如WO 2015/189114所記載而進行。
較佳為進行如下反應順序以製備式(III)之化合物：
實施例
藉由後述實施例更詳細地闡明本發明，但本發明不限於此等實施例。
3-氯-2-乙烯苯酚(Ia)
在20℃下將氫氧化鉀粉末(85%,22.6g，342.9mmol)添加至4-氯-2,3-二氫-1-苯并呋喃(IIa)(19.0g，114.3mmol)於N,N-di甲基乙醯胺(75ml)之溶液中，將該混合物加熱至120℃並在此溫度下攪拌1小時。將反應混合物冷卻到約10-15℃，用水(150ml)稀釋，並藉由緩慢地添加37%氫氯酸(40ml)達到pH為1。用甲苯(每次各100ml)萃取水相兩次，以10%氫氯酸(30ml)清洗結合的有機相一次，且在減壓下濃縮至殘餘體積約100ml。如此獲得的溶液係在接下來步驟中直接使用。3-氯-2-乙烯苯酚之分析數據如下：1H-NMR(CDCl3,400MHz)δ(ppm)=7.08(dd,J=8.0,8.0Hz,1H),6.96(d,J=8.0Hz,1H),6.84(d,J=8.0Hz,1H),6.79(dd,J=12.0Hz,12.0Hz,1H),5.74(d,J=12.0Hz,1H),5.73(s,1H),5.68(d,J=12.0Hz,1H)。
3-Bromo-2-乙烯苯酚(Ib)
1H-NMR(DMSO-d6,400MHz)δ(ppm)=10.20(s,1H),7.08(dd,J=8.0,1.3Hz,1H),6.99(t,J=8.0Hz,1H),6.89(dd,J=8.0,1.0Hz,1H),6.77(dd,J=17.8,12.1Hz,1H),6.08(dd,J=17.8,2.5Hz,1H),5.51(dd,J=12.1,2.5Hz,1H)。
3-甲基-2-乙烯苯酚(Ic)
1H-NMR(DMSO-d6,400MHz)δ(ppm)=9.45(s,1H),6.93(t,J=7.8Hz,1H),6.73(dd,J=17.9,11.8Hz,1H),6.69(d,J=7.8,1.0Hz,1H),6.63(d,J=7.8Hz,1H),5.76(dd,J=17.9,2.5Hz,1H),5.41(dd,J=11.9,2.5Hz,1H),2.27(s,3H)。
3-氯-2-乙烯基苯基甲烷磺酸酯(IIIa)
將上述步驟獲得的Ia之甲苯溶液冷卻至0-5℃，並添加三乙胺(17.5ml，125.7mmol)。在0-5℃之溫度下於超過1小時的期間計量甲烷硫醯氯(9.7ml,125.7mmol)於甲苯中的50%溶液，並在添加結束後，將混合物在20℃下攪拌30分鐘。接著， 藉由在10-15℃緩慢添加10%氫氯酸(50ml)達到反應混合物之pH為1，並且以甲苯/tert-丁基甲基醚4：1(每次各50ml)之混合物萃取水相兩次。在減壓下濃縮結合的有機相，且自乙醇(15ml)(23.7g，理論值之89%)再結晶殘餘物。1H-NMR(CDCl3,400MHz)δ(ppm)=7.36(dd,J=8.0,1.2Hz,1H),7.34(dd,J=8.0,1.2Hz,1H),7.23(t,J=8.0Hz,1H),6.76(dd,J=18.0Hz,11.7Hz,1H),5.91(dd,J=18.0,1.6Hz,1H),5.73(dd,J=11.8,1.4Hz,1H),3.11(s,3H)。
3-溴-2-乙烯基苯基甲烷磺酸酯(IIIb)
1H-NMR(CDCl3,400MHz)δ(ppm)=7.56(dd,J=8.1,1.1Hz,1H),7.38(dd,J=8.1,1.1Hz,1H),7.16(t,J=8.1Hz,1H),6.72(dd,J=18.0Hz,11.8Hz,1H),5.84(dd,J=18.0,1.4Hz,1H),5.71(dd,J=11.6,1.4Hz,1H),3.11(s,3H)。
3-甲基-2-乙烯基苯基甲烷磺酸酯(IIIc)
1H-NMR(CDCl3,400MHz)δ(ppm)=7.23(dd,J=7.8,1.8Hz,1H),7.18(t,J=7.8Hz,1H),7.14(dd,J=7.5,1.4Hz,1H),6.71(dd,J=17.8Hz,11.8Hz,1H),5.65(dd,J=11.8,1.6Hz,1H),5.63(dd,J=17.8,1.6Hz,1H),3.09(s,3H),2.37(s,3H)。
Claims (7)
- 一種製備式(I)之經取代之苯乙烯衍生物的方法，
- 根據請求項1之方法，其特徵在於式(I)與(II)之基團定義係如下：R1 為Cl。
- 根據請求項1或2之方法，其特徵在於所使用的鹼為tert-丁氧化鉀、tert-丁氧化鈉、甲氧化鈉、乙氧化鈉、甲氧化鉀或氫氧化鉀。
- 根據請求項1或2之方法，其特徵在於醯胺、或醚溶劑、或醯胺溶劑與醚類之混合物、或芳族溶劑係用作為溶劑。
- 根據請求項1或2之方法，其特徵在於所使用的溶劑為DMAc，DMF，或二甘二甲醚，或DMAc或DMF與THF、2-甲基-THF、二噁烷、DME、甲苯、二甲苯、氯苯或1,2-二氯苯之混合物。
- 根據請求項1或2之方法，其特徵在於溶劑與鹼之下列組合係用於反應：a)二甘二甲醚與氫氧化鉀之組合，b)DMAc與氫氧化鉀之組合，c)DMF與氫氧化鉀之組合，d)DMAc與甲苯、二甲苯、氯苯、1,2-二氯苯、二噁烷、DME、2-甲基-THF或THF之溶劑混合物以及氫氧化鉀之組合，e)DMF與甲苯、二甲苯、氯苯、1,2-二氯苯、二噁烷、DME、2-甲基-THF或THF之溶劑混合物以及氫氧化鉀之組合，f)DMAc、DMF、THF、2-甲基-THF、二噁烷、DME、苯甲醚或二甘二甲醚或此等溶劑之混合物與tert-丁氧化鉀之組合。
- 根據請求項3之方法，其特徵在於氫氧化鉀係用作為無機鹼，且tert-丁氧化鉀係用作於有機鹼。
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