CN1023802C - 制备5-取代-3-糠醛的方法 - Google Patents
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- -1 5-substituted-3-furaldehydes Chemical class 0.000 title claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- AXSMTZCJJBPZAA-UHFFFAOYSA-N lithium;morpholin-4-ide Chemical compound [Li]N1CCOCC1 AXSMTZCJJBPZAA-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 23
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001356 alkyl thiols Chemical class 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 150000002240 furans Chemical class 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- AZVSIHIBYRHSLB-UHFFFAOYSA-N 3-furaldehyde Chemical compound O=CC=1C=COC=1 AZVSIHIBYRHSLB-UHFFFAOYSA-N 0.000 abstract description 21
- 239000012039 electrophile Substances 0.000 abstract 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 238000003756 stirring Methods 0.000 description 22
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 150000002780 morpholines Chemical class 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 235000012239 silicon dioxide Nutrition 0.000 description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- FGJIDQWRRLDGDB-CPIXEKRISA-N manoalide Chemical compound C=1([C@@H](O[C@H](CC=1)C=1[C@@H](OC(=O)C=1)O)O)CC\C=C(/C)CCC1=C(C)CCCC1(C)C FGJIDQWRRLDGDB-CPIXEKRISA-N 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CZPSACMHRFQGBH-UHFFFAOYSA-N [SiH3]C=1OC=CC=1CO Chemical class [SiH3]C=1OC=CC=1CO CZPSACMHRFQGBH-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 229960003328 benzoyl peroxide Drugs 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- VAOPEQGLAIKHQE-UHFFFAOYSA-N bromobenzene formaldehyde Chemical compound C=O.BrC1=CC=CC=C1 VAOPEQGLAIKHQE-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- FGJIDQWRRLDGDB-GMKZXUHWSA-N manoalide Natural products CC(=CCCC1=CC[C@@H](O[C@H]1O)C2=CC(=O)O[C@H]2O)CCC3=C(C)CCCC3(C)C FGJIDQWRRLDGDB-GMKZXUHWSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- YUPOCHDBBHTUBJ-UHFFFAOYSA-N nonadecan-10-one Chemical compound CCCCCCCCCC(=O)CCCCCCCCC YUPOCHDBBHTUBJ-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- ARVVVVWAVZGHFV-UHFFFAOYSA-N 4-phenyl-3,8-dithiatricyclo[5.1.0.02,4]oct-5-ene Chemical compound S1C2C3SC3C=CC21C1=CC=CC=C1 ARVVVVWAVZGHFV-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 229910006404 SnO 2 Inorganic materials 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- STJIISDMSMJQQK-UHFFFAOYSA-N furan-3-ylmethanol Chemical group OCC=1C=COC=1 STJIISDMSMJQQK-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
- C07D307/48—Furfural
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/0827—Syntheses with formation of a Si-C bond
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
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Abstract
一种制备5-取代-3-糠醛的方法,该方法包括用3-糠醛与锂酰吗啉反应,接着与仲-丁基锂反应,然后再与亲电子试剂反应。
Description
本发明涉及一种制备5-取代-3-糠醛的新方法。这些化合物用作制备药物活性的呋喃酮的中间产品。例如5-三烷基甲硅烷基-3-糠醛用来制备具有抗炎活性的manoalide和manoalide类化合物的中间产品。
由Comins等人在有机化学杂志52:104-109(1987)中报道3-糠醛的金属取代物(锂化)在二位具有高的区域选择性。
由Goldsmith等人于Tetrahedron letters 24:5835-5838(1983)中报道首先用苯基氢硫基团来封闭3-羟基甲基呋喃的2-位,然后,引入三甲基甲硅烷基基团进入5-位,并从2-位除去苯基氢硫基来制备5-三甲基甲硅烷基-3-羟基甲基呋喃。由Katsumura等人于Tetrahedron Letters26:5827-5830(1985)中在合成manoalide中采用的这种多步法来制备5-三甲基甲硅烷基-3-羟基甲基呋喃,然后氧化上述产物而得到5-三甲基甲硅烷基-3-糠醛。
本发明涉及一种制备5-取代-3-糠醛化合物的新方法,这种方法可以在单缸过程中来加工完成,而没有中间产品析出。从上述现有技术的揭示中,不能预料在本发明的方法中,金属取代发生在3-糠醛的5-位上,5-取代的-3-糠醛是从3-糠醛制备而不用封闭2-位。
本发明的方法可描述如下:
一种制备5-取代的-3-糠醛的方法,其分子式为:
式中E是亲电子基团,该方法包括3-糠醛和
(1)锂铣吗啉反应,接着和
(2)次一丁基锂反应,再接着和
(3)亲电子试剂反应。
本发明中典型的亲电子基团(E)是三烷基甲硅烷基;三烷基甲锡烷基;C1-20烷基;C1-20链烯基或是炔基,所说的,双键或三键在C2或大于C2的碳基团上;或在苯环上由卤素,低级烷基或低级烷氧基,N-烷基氨基甲酰基,烷基巯基,苯基巯基或链烷酰基任意取代的苯甲基。
本发明的方法可以采用的亲电子试剂的实例是卤化物、醛、酮、异氰酸酯、环氧化物、二硫化物和酯。
在本发明的方法中可以采用的特定的亲电子试剂是:
三甲基甲硅烷基氯化物
三乙基甲硅烷基氯化物
叔-丁基二甲基-甲硅烷基氯化物
三丁基甲锡烷基氯化物
1-碘辛烷
2-十一烷酮
4-溴代苯甲醛
1-己醛
本发明的方法可按下述进行:
将3-糠醛加入锂酰吗啉溶液中,该溶液按下
述制得:在一适合的溶剂中,如四氢呋喃中,在一惰性气体下如氩气,降低温度使正-丁基锂(在一惰性溶剂如己烷中)同吗啉反应而得到锂酰吗啉溶液。大约15-30分钟后,将在溶剂如环己烷中的仲-丁基锂加入,降低温度搅拌反应混合物约1-8小时,然后加入亲电子试剂。连续搅拌8-40小时,最好10-20小时,同时使反应混合物的温度上升到室温。上述提到的降低的温度大约为-78℃。
由Katsumura等人描述了5-取代的-3-糠醛作为中间产品的使用,如上所述,他们在合成manoalied及manoalide类化合物中使用5-三甲基甲硅烷基-3-糠醛。具有抗炎活性的Manoalied类化合物也是由5-取代-3-糠醛同烷基镁溴化物和乙酐反应而制得2-三甲基甲硅烷基-4-α-乙酸基烷基呋喃。该产物用纯氧处理得到4-α-乙酸基烷基-5-羟基-2(5H)-呋喃酮。
本发明的方法为下列实例证明但不限于下列实例。在下文中温度均为摄氏温度。
实例1
5-三甲基甲硅烷基-3-糠醛。
将正-丁基锂(2.5M己烷溶液;28.8毫升,72毫摩尔)在氩气下于-78°加入到溶于四氢呋喃(700毫升)的吗啉(6.28毫升,72毫摩尔)溶液中。20分钟后,加入3-糠醛(7.0克,72毫摩尔),再20分钟分,将仲-丁基锂(1.3M环己烷溶液;55.4毫升,72毫摩尔)滴入,于-78°下连续搅拌7小时后,加入三甲基甲硅烷基氯化物(27毫升,216毫摩尔)。连续搅拌过夜(14小时)同时使冷浴升至室温。溶液中注入含冰10%的(V/V)盐酸(200毫升),然后在0°下搅拌10分钟,分层。用二乙基醚萃取水相。全部有机相混合,干燥(硫酸镁)和蒸馏后得到一种淡棕色油。再使用2%乙基醚/己烷在二氧化硅上通过闪色谱分离提纯上述油,通过蒸馏而得到Rf约为0.30(二氧化硅,10%乙基醚/己烷)的分馏物的淡黄色油的标题醛。
1H NMR(CDCl3)0.29(S,9H),6.98(S,1H),8.25(S,1H)和9.95(S,1H)。
13C NMR(CDCl3)-2.0,116.2,128.9,155.3,164.1和184.5。
MS精确计算的C8H12O2Si(M+)的168.0607的质量实测值为168.0588。
实例2
5-三乙基甲硅烷基-3-糠醛
将正-丁基锂(2.5M己烷溶液;30.6毫升,76.5毫摩尔)在氩气下,于-78°加入吗啉(6.66毫升,76.5毫摩尔)的四氢呋喃(500毫升)溶液中。15分钟后,加入3-糠醛(6.3毫升,72.8毫摩尔)。再20分钟后,滴入仲-丁基锂(1.3M环己烷溶液;59.0毫升,76.5毫摩尔),在-78°下连续搅拌7小时后,加入三乙基甲硅烷基氯化物(13.4毫升,80.1毫摩尔)。连续搅拌过夜(14小时),同时,使冷浴升至室温,溶液中注入含冰10%(V/V)的盐酸(100毫升),在0°下搅拌10分钟后,分层。用二乙基醚萃取水相。混合全部有相,干燥(硫酸镁)并蒸发得到一种油,在高真空蒸馏这种油得到5-三乙基甲硅烷基-3-糠醛的浅黄色油,沸点85-90°/0.4托。
IR(净):1680cm-1
1H NMR(CDCl3) 0.79(q,6H,J=7.3Hz),0.9(t,9H,J=7.3Hz),7.0(S,1H),8.26(S,1H)和9.95(S,1H)。
13C NMR(CDCl3)2.9,7.1,117.2,128.8,155.6,162.3和184.6。
MS m/e精确计算C11H18O2Si(M+)210.1076的质量实测为210.1071。
实例3
5-(叔-丁基二甲基甲硅烷基)-3-糠醛
将正-丁基锂(2.5M己烷溶液;8.3毫升,20.8毫摩尔)在氩气下于-78°加入吗啉(1.81毫升,20毫摩尔)的四氢呋喃(100毫升)溶液中。20分钟后,加入3-糠醛(1.8毫升,20.8毫摩尔)。再15分钟后,滴入仲-丁基锂(1.3M环己烷溶液;16.8毫升,21.9毫摩尔),在-78°下连续搅拌1小时后,加入叔-丁基二甲基甲硅烷基氯化物(9.4克,62.4毫摩尔)的四氢呋喃(10毫升)溶液中。连续搅拌过夜(16小时)同时,使冷浴升至室温。溶液中注入含冰10%(V/V)盐酸(40毫升),之后在0°下搅拌10分钟,分层。用二乙基醚萃取水相。混合整个有机相,干燥(硫酸镁)和蒸发后得到棕色油,在高真空下蒸馏油得到标题的醛,其沸点80-5°/0.5乇,熔点37-8°。
1H NMR(CDCl3) 0.23(S,6H),0.9(S,9H),6.99(S,1H),8.25(S,1H),和9.94(S,1H)
13C NMR(CDCl3)16.6,26.1,117.3,128.8,155.5,162.7和184.5。
MS精确计算C11H18O2Si(M+)210.1076的质量实测为210.1075。
实例4
5-(正-三丁基甲锡烷基)-3-糠醛
将正-丁基锂(2.5M己烷溶液;8.7毫升,22毫摩尔)在氩气下于-78°加入吗啉(1.9毫升,22毫摩尔)的四氢呋喃(80毫升)溶液中。15分钟后,加入3-糠醛(1.8毫升,21毫摩尔)。再20分钟后,滴入仲-丁基锂(1.3M环己烷溶液;19.2毫升,25毫摩尔),在-78°下连续搅拌4小时,然后加入三丁基甲锡烷基氯化物(8.5毫升,31毫摩尔),在室温下连续搅拌40小时。溶液中注入含冰10%(V/V)盐酸(30毫升),在0°搅拌10分钟后分层。用二乙基醚萃取水相。混合整个有机相,干燥(硫酸镁)和蒸发后得到油,再使用5%的乙基醚/己烷于二氧化硅上用闪色谱分离法提纯上述油。通过蒸发,得到Rf大约为0.27的分馏物的标题的化合物,为极淡黄色的油。
1H NMR(CDCl3) 0.93(m,9H),1.15(m,6H),1.35(m,6H),1.65(m,6H),6.95(S,1H),8.35(S,1H)和9.99(S,1H)。
13C NMR(CDCl3)10.1,13.5,17.5,26.6,26.7,27.0,27.4,27.8,28.6,28.7,28.9,117.8,128.7,156.3,165.2,和184.4。
IR(净)2720-2800,1675(S,S)和1125(S,S)。
MS精确计算C17H30SnO2(M+)384.1257的质量实测为384.1252。
实例5
5-辛基-3-糠醛。
将正-丁基锂(2.5M己烷溶液;4.37毫升,10.9毫摩尔)在氩气下于-78°加入吗啉(0.91毫升,10.4毫摩尔)的四氢呋喃(40毫升)的溶液中。20分钟后,加入3-糠醛(0.9毫升,10.4毫摩尔)。又20分钟后滴入仲-丁基锂(1.3M环己烷溶液;8.4毫升,10.9毫摩尔),在-78°下连续搅拌4小时,然后,加入1-碘辛烷(2.07毫升,11.4毫摩尔)。连续搅拌过夜(17小时),同时使冷浴升至室温。溶液中注入含冰10%(V/V)盐酸(15毫升),在0°下搅拌10分钟后,分层。用二乙基醚萃取水相,混合所有有机相。干燥(硫酸镁)和蒸发后得到油,再使用10%乙基醚/己烷于二氧化硅上通过闪色谱分离法提纯上述油,通过蒸发得到Rf为0.23的分馏物标题的化合物,为无色的针状体。熔点25°(己烷)。
1H NMR(CDCl3) 0.93(t,3H,J=7.2Hz),1.32(br,10H),1.67(t,2H,J=7.1Hz),2.68(t,2H,J=7.8Hz),6.43(S,1H),7.98(S,1H)和9.92(S,1H)。
13C NMR(CDCl3)13.6,22.2,27.1,27.3,28.6,28.7,28.8,31.4,101.3,129.2,149.9,159.0和183.9。
MS精确计算C13H20O2(M+)为208.1463的质量实测为208.1454。
实例6
5-(1-羟基-1-甲基癸基)-3-糠醛
将正-丁基锂(2.5M己烷溶液;4.37毫升,10.9毫摩尔)在氩气下于-78°加入吗啉(0.91毫升,10.4毫摩尔)的四氢呋喃(40ml)溶液中。20分钟后,加入3-糠醛(0.9毫升,10.4毫摩尔)。再20分钟后,滴入仲-丁基锂(1.3M环己烷;8.4毫升,10.9毫摩尔),在-78°下连续搅拌7小时后加入2-十一烷酮(2.36毫升,11.4毫摩尔)。连续搅拌过夜(17小时),同时使冷浴升至室温。溶液中注入含冰10%(V/V)的盐酸(30毫升),在0°下搅拌10分钟后分层。用二乙醚萃取水相。混合全部有机相,干燥(硫酸镁)和蒸发后得到油。在二氧化硅上用闪色谱分离法提纯上述油。通过蒸发得到Rf约为0.07的分馏物的标题的化合物,为黄色油。
1H NMR(CDCl3) 0.91(t,3H,J=7.0Hz),1.28(brs,14H),1.58(S,3H),1.85(m,2H),2.10(br,1H),6.62(S,1H),8.03(S,1H)和9.93(S,1H)。
13C NMR(CDCl3)13.9,22.5,23.9,26.1,29.1,29.3,29.6,31.4,31.7,41.2,71.2,101.4,128.9,150.7,162.8和184.7。
MS精确计算C16H26O3(M+)为266.1881的质量实测值为266.1873。
实例7
5-[(4-溴代苯基)-1-羟基甲基]-3-糠醛。
将正-丁基锂(2.5M己烷溶液;4.37毫升,10.9毫摩尔)在氩气下于-78°加入吗啉(0.91毫升,10.4毫摩尔)的四氢呋喃(30毫升)溶液中。20分钟后,加入3-糠醛(0.91毫升,10.4毫摩尔)。再20分钟后滴入仲-丁基锂(1.3M环己烷溶液;8.4毫升;10.9毫摩尔),并在-78°下连续搅拌4小时后,加入4-溴代苯甲醛(2.11克,11.4毫摩尔)的四氢呋喃(10ml)溶液中。连续搅拌过夜(17小时)M时使冷浴升至室温。溶液中注入含冰10%(V/V)的盐酸(30毫升),在0°下搅拌10分钟后分层。用二乙醚萃取水相。混合整个有机相,干燥(硫酸镁)和蒸发后得到油。再使用40%的乙酸乙酯/己烷于二氧化硅上用闪色谱提纯上述油。通过蒸发而得到Rf约为0.23的分馏物的标题的化合物,一种黄色固体,熔点83-4°(由氯仿重结晶)。
1H NMR(CDCl3)2.85(br,1H),5.83(S,1H),6.56(S,1H),7.34(d,2H,J=8.4HZ),7.55(d,2H,J=8.4Hz),8.05(S,1H)和9.89(S,1H)。
13C NMR(CDCl3)68.6,103.9,121.9,128.0,128.5,131.4,138.8,151.7,158.2和184.9。
MS精确计算C12H9BrO3(M+)质量279.9735的实测为279.9741。
实例8
5-(1-羟基己基)-3-糠醛
将正-丁基锂(2.5M己烷溶液;4.37毫升,10.9毫摩尔)在氩气下于-78°加入吗啉(0.91毫升,10.9毫摩尔)的四氢呋喃(30毫升)中。20分钟后,加入3-糖醛(0.9毫升,10.4毫摩尔)。再20分钟后,滴入仲-丁基锂(1.3M环己烷溶液;8.4毫升,10.9毫摩尔),在-78°下连续搅拌7小时,后加入1-己醛(1.31毫升,10.9毫摩尔)。连续搅拌过夜(16小时),同时使冷浴升至室温。溶剂中注入含冰10%(V/V)的盐酸(30毫升),在0°下搅拌10分钟,分层。用二乙基醚萃取水相。混合所有有机相,干燥(硫酸镁)和蒸发后得到棕色油。再用40%的乙基醚/己烷于二氧化硅上用闪色谱法分离提纯上述油。通过蒸馏得到Rf约为0.08的分馏物的标题的化合物,为黄色油。
1H NMR(CDCl3)0.91(br,3H),1.35(brm 6H),1.86(m,2H),2.25(br,1H),4.72(t,1H),6.74(S,1H),8.05(S,1H)和9.92(S,1H)。
13C NMR(CDCl3)13.8,22.4,24.9,31.4,35.2,67.2,102.5,128.9,151.1,160.0和184.8,
MS精确计算C11H16O3(M+)为196.1099的质量实测为196.1099。
实例9
按照实例8的方法,用异氰酸甲酯代替1-己醛制备5-N-甲基氨基甲酰基-3-糠醛。
实例10
按实例8的方法,用二苯基二硫化物代替1-己醛制备5-苯基氢硫基-3-糠醛。
实例11
按实例8的方法,用乙酸甲酯代替1-己醛制备5-乙酰基-3-糠醛
同样地,用2,2-二甲基乙烯氧化物代替1-己醛,制备5-(2-羟基-2-甲基)丙基-3-糠醛。
Claims (6)
2、按照权利要求1的方法,其特征在于是E是三烷基甲硅烷基;三烷基甲锡烷基;烷基巯基,苯基巯基或链烷酰基任意取代的苯甲基。
3、按照权利要求2的方法,其特征在于是E是三甲基甲硅烷基,三乙基甲硅烷基,或叔-丁基二甲基甲硅烷基。
4、按照权利要求3的方法,其特征在于是E是三甲基甲硅烷基和亲电子试剂是三甲基甲硅烷基氯化物。
5、按照权利要求2的方法,其特征在于是E是三丁基甲锡基烷基。
6、按照权利要求1的方法,其特征是亲电子试剂是卤化物。
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US259,225 | 1988-10-18 | ||
US07/259,225 US4935530A (en) | 1988-10-18 | 1988-10-18 | Process for preparing 5-substituted-3-furaldehydes |
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US (1) | US4935530A (zh) |
EP (1) | EP0365256B1 (zh) |
JP (1) | JPH02164876A (zh) |
KR (1) | KR900006311A (zh) |
CN (1) | CN1023802C (zh) |
AT (1) | ATE94552T1 (zh) |
AU (1) | AU614474B2 (zh) |
CA (1) | CA2000677A1 (zh) |
DE (1) | DE68909166T2 (zh) |
DK (1) | DK517889A (zh) |
ES (1) | ES2044137T3 (zh) |
FI (1) | FI894924A0 (zh) |
HU (1) | HU204806B (zh) |
IE (1) | IE63693B1 (zh) |
IL (1) | IL91981A0 (zh) |
NO (1) | NO172799C (zh) |
NZ (1) | NZ231026A (zh) |
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US5134128A (en) * | 1987-06-08 | 1992-07-28 | Allergan, Inc. | Anti-inflammatory furanones |
US5082954A (en) * | 1987-06-08 | 1992-01-21 | Allergan, Inc. | Intermediates and processes for preparing 4-substituted 2-5(H)-furanones as anti-inflammatory agents |
US5322953A (en) * | 1987-06-08 | 1994-06-21 | Allergan, Inc. | 2-trialkylsilyl-3-furaldehydes |
US5171863A (en) * | 1987-06-08 | 1992-12-15 | Allergan, Inc. | Intermediates for preparing 4-substituted 2-5(H)-furanones as anti-inflammatory agents |
US5037811A (en) * | 1990-04-17 | 1991-08-06 | Allergan, Inc. | 4-(oxygen, sulfur or nitrogen substituted)-methyl 5-hydroxy-2(5H)-furanones as anti-inflammatory agents |
US5043457A (en) * | 1990-04-17 | 1991-08-27 | Allergan, Inc. | 2(5H)-furanones substituted in the 3 position, as Ca2+ channel antagonists and anti-inflammatory agents |
US5045564A (en) * | 1988-12-07 | 1991-09-03 | Allergan, Inc. | Anti-inflammatory 2-furanones |
US5258400A (en) * | 1989-11-20 | 1993-11-02 | Allergan, Inc. | Anti-inflammatory furanone compounds |
US5112853A (en) * | 1989-11-20 | 1992-05-12 | Allergan, Inc. | Anti-inflammatory furanone compounds |
US5225571A (en) * | 1991-04-30 | 1993-07-06 | Allergan, Inc. | Substituted dihydroxy-bis-[5-hydroxy-2(5H)-furanone-4-yl]-alkanes as anti-inflammatory agents |
US5183906A (en) * | 1991-04-30 | 1993-02-02 | Allergan, Inc. | 2- and 5-alkyl and phenyl substituted 4-(1-hydroxy, 1-acyloxy or 1-carbamoyloxy)-5-hydroxy-2 (5h)-furanones as anti-inflammatory agents |
US5169963A (en) * | 1991-08-30 | 1992-12-08 | Allergan, Inc. | Di-(5-hydroxy-2(5H)2-oxo-4-furyl)alkylmethyl-alpha,omega alkanedioates and N,N-bis-(5-hydroxy-2(5H)2-oxo-4-furyl)alkylmethyl-alpha,omega-dialkanoic acid amides as anti-inflammatory agents |
US5171864A (en) * | 1991-08-30 | 1992-12-15 | Allergan, Inc. | Di-(5-hydroxy-2(5H)-2-oxo-4-furyl)methyl-alpha,omega alkane-dioates and N,N-bis-(5-hydroxy-2(5H)-2-oxo-4-furyl)methyl-alpha,omega-dialkanoic acid amides as anti-inflammatory agents |
US5268387A (en) * | 1992-04-24 | 1993-12-07 | Allergan, Inc. | Pharmaceutical compositions and method for administering 3 and 4-substituted 2(5H)-furanones to a mammal for inhibiting bone loss |
US5451686A (en) * | 1994-04-15 | 1995-09-19 | Allergan, Inc. | 3 and 5 alkyl and phenyl 4-(hydroxy or acyloxy)-alkyl substituted 2(5H)-furanones as anti-inflammatory agents |
US5639468A (en) * | 1995-06-07 | 1997-06-17 | University Of Southern California | Method for reducing or preventing post-surgical adhesion formation using manoalide and analogs thereof |
US7317116B2 (en) * | 2004-12-10 | 2008-01-08 | Archer-Daniels-Midland-Company | Processes for the preparation and purification of hydroxymethylfuraldehyde and derivatives |
US7393963B2 (en) * | 2004-12-10 | 2008-07-01 | Archer-Daniels-Midland Company | Conversion of 2,5-(hydroxymethyl)furaldehyde to industrial derivatives, purification of the derivatives, and industrial uses therefor |
KR101463933B1 (ko) * | 2012-08-14 | 2014-11-26 | 한국과학기술원 | 5-치환된 또는 2,5-치환된 3-푸르알데히드 유도체의 제조방법 |
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US4221585A (en) * | 1978-08-04 | 1980-09-09 | E. I. Du Pont De Nemours And Company | N-[(2,6-Dimethoxypyrimidin-4-yl)]aminocarbonyl benzene sulfonamides and their herbicidal compositions and methods of use |
US4195026A (en) * | 1978-12-04 | 1980-03-25 | Iowa State University Research Foundation, Inc. | Substituted furans from butenolides |
US4500520A (en) * | 1983-03-01 | 1985-02-19 | E. I. Du Pont De Nemours And Company | Antiinflammatory and/or analgesic silylfurans |
EP0299974B1 (en) * | 1986-04-07 | 1992-01-22 | The Upjohn Company | Anthelmintic acylhydrazones, method of use and compositions |
GB8609452D0 (en) * | 1986-04-17 | 1986-05-21 | Ici Plc | Fungicides |
CA1329390C (en) * | 1987-06-08 | 1994-05-10 | John N. Bonfiglio | Anti-inflammatory furanones |
-
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- 1989-10-16 NZ NZ231026A patent/NZ231026A/en unknown
- 1989-10-16 EP EP89310601A patent/EP0365256B1/en not_active Expired - Lifetime
- 1989-10-16 AT AT89310601T patent/ATE94552T1/de not_active IP Right Cessation
- 1989-10-16 ES ES89310601T patent/ES2044137T3/es not_active Expired - Lifetime
- 1989-10-16 DE DE89310601T patent/DE68909166T2/de not_active Expired - Fee Related
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DK517889D0 (da) | 1989-10-18 |
HUT51266A (en) | 1990-04-28 |
PT92016B (pt) | 1995-06-30 |
CN1042154A (zh) | 1990-05-16 |
EP0365256B1 (en) | 1993-09-15 |
US4935530A (en) | 1990-06-19 |
DE68909166D1 (de) | 1993-10-21 |
AU4296889A (en) | 1990-05-10 |
DE68909166T2 (de) | 1994-02-10 |
NO894133D0 (no) | 1989-10-17 |
ATE94552T1 (de) | 1993-10-15 |
NO172799B (no) | 1993-06-01 |
NO894133L (no) | 1990-04-19 |
DK517889A (da) | 1990-04-19 |
ZA897768B (en) | 1990-07-25 |
NZ231026A (en) | 1991-05-28 |
AU614474B2 (en) | 1991-08-29 |
JPH02164876A (ja) | 1990-06-25 |
KR900006311A (ko) | 1990-05-07 |
FI894924A0 (fi) | 1989-10-17 |
CA2000677A1 (en) | 1990-04-18 |
IL91981A0 (en) | 1990-07-12 |
EP0365256A1 (en) | 1990-04-25 |
IE63693B1 (en) | 1995-05-31 |
HU895337D0 (en) | 1990-01-28 |
ES2044137T3 (es) | 1994-01-01 |
NO172799C (no) | 1993-09-08 |
IE893335L (en) | 1990-04-18 |
HU204806B (en) | 1992-02-28 |
PT92016A (pt) | 1990-04-30 |
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