CN1064673A - 羧酸酯的还原方法 - Google Patents
羧酸酯的还原方法 Download PDFInfo
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- CN1064673A CN1064673A CN92102604A CN92102604A CN1064673A CN 1064673 A CN1064673 A CN 1064673A CN 92102604 A CN92102604 A CN 92102604A CN 92102604 A CN92102604 A CN 92102604A CN 1064673 A CN1064673 A CN 1064673A
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- 239000002253 acid Substances 0.000 claims description 31
- 239000007864 aqueous solution Substances 0.000 claims description 22
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 21
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 20
- 238000007254 oxidation reaction Methods 0.000 claims description 20
- 229910052783 alkali metal Inorganic materials 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 16
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- SYNHCENRCUAUNM-UHFFFAOYSA-N Nitrogen mustard N-oxide hydrochloride Chemical compound Cl.ClCC[N+]([O-])(C)CCCl SYNHCENRCUAUNM-UHFFFAOYSA-N 0.000 claims 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- 229910052759 nickel Inorganic materials 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N noncarboxylic acid Natural products CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
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- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/26—Quinones containing groups having oxygen atoms singly bound to carbon atoms
- C07C50/28—Quinones containing groups having oxygen atoms singly bound to carbon atoms with monocyclic quinoid structure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
- C07C46/02—Preparation of quinones by oxidation giving rise to quinoid structures
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
- C07C46/02—Preparation of quinones by oxidation giving rise to quinoid structures
- C07C46/04—Preparation of quinones by oxidation giving rise to quinoid structures of unsubstituted ring carbon atoms in six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C46/00—Preparation of quinones
- C07C46/02—Preparation of quinones by oxidation giving rise to quinoid structures
- C07C46/06—Preparation of quinones by oxidation giving rise to quinoid structures of at least one hydroxy group on a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
本发明的涉及生产式(Ⅲ)化合物的方法。
用此方法制得的产品化合物的产率高,对工业生
产有利。
Description
本发明涉及在合成药物时用作中间原料的10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1及其同类物的生产方法。
6-(10-羟癸基)-2,3-二甲氧基-5-甲基-1,4-苯酯(idebenone)已被公认是一种具有特殊药理活性的化合物,如其台增强免疫力,使肌肉松弛,对损伤组织,尤其是对心脏肌肉和组织,有使酶活化的作用,已知以工业方式生产idebenone的方法(Toku-Kai-Sho 59-39855)如下:
(第1步)-将-9(2-羟基-3,4-二甲氧基-6-甲基-苯甲酰基)壬酸烷基酯加以还原,产生10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸酸烷基酯。
(第2步)-产物用氢化双(2-甲氧乙氧基)铝钠(Vitride)作进一步还原,生成10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1。
(第3步)-将此新产物氧化,得到idebenone。
上述第2步中使用氢化双(2-甲氧乙氧基)铝钠有安全方面的问题,因为此化合物容易与空气中的水分发生作用放出氢而引燃。另外,此化合物又是一种特殊试剂,在稳定供应上也有困难。考虑到这些缺点,本发明者于是进行了各方面的研究,发现采用硼氢化钠与氯化铝的混合物作为还原剂,应用于生产10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1及其同类物时,可得到令人满意的产率,并可工业规模生产。
本发明是有关下式化合物的生产方法:
式中R1和R2各代表一个低级烷基;n表示0至21的整数,X代表氢原子或一任意被保护的羟基;Y代表一任意被保护的羟基,该方法包括如何用硼氢化钠与氯化铝混合物还原下式所示酯类化合物:
式中R1、R2、n、X和Y代表与上述相同的含义,R3代表低级烷基。
上述(Ⅰ)式和(Ⅱ)式中R1、R2和R3所代表的低级烷基的实例包括碳原子数1至4的烷基,诸如甲基、乙基、丙基等基团;X和Y代表的任意被保护的羟基除自由羟基外,例如有碳原子数1至3的低级烷氧基(甲氧基,乙氧基等),碳原子数为2至4的低级酰氧基(乙酰氧基、丙酰氧基等),碳原子数从3至6的硅烷氧基(三甲基硅烷氧基等),甲氧基甲基氧等,n代表0至21的整数,以8至12最佳。
本发明的还原反应最好在适当的溶剂中进行。任何能溶解起始化合物(Ⅰ)而不阻碍反应进行的溶剂均可选用。此类溶剂的实例包括醚类如乙醚,四氢呋喃、二氧杂环己烷等,以及苯、甲苯、二甲苯等芳烃类。反应温度一般在0°至140℃之间,以10°至40℃为最佳。硼氢化钠用量一般不少于起始化合物(Ⅰ)摩尔数的1.5倍,取其摩尔数的2倍量左右为好。氯化铝的用量最好是使其与硼氢化钠的摩尔比约为1∶3。
若体系中有少量水存在,反应的结果更好。更具体地说,水的存在抑制了不期望的副反应产物(即式(Ⅱ)化合物,其中R1和R2中之一是氢或两者均是氢)的生成,因而期望的化合物(Ⅱ)的产率便得到进一步的改善。所加入的水量一般在0.1至1.7倍摩尔数的范围内,最好是0.2至1.5倍。加入过量水,期望的化合物不能获得高产量,而且反应时间拖长。
本发明所得的化合物(Ⅱ)可以用能将酚转化成醌而不影响醇羟基的氧化剂进行氧化,可导至下式化合物的生成
式中符号所代表的意义同上。这些氧化剂可以是氧化银、氯化高铁、二氧化锰、亚硝基二磺酸盐等,其中以亚硝基二磺酸的二碱金属盐为最可取,这化合物可通过电解羟胺二磺酸二碱金属的水溶液,使之进行氧化反应的方法得到。
下面是采用通过电解氧化羟胺二磺酸二碱金属盐水溶液而得到的亚硝基二磺酸二碱金属盐作为氧化剂对化合物(Ⅱ)进行氧化反应的说明。
羟胺二磺酸二碱金属盐可以二钠盐或二钾盐为例,而亚硝基二磺酸二碱金属盐也可以二钠盐或二钾盐为例,以选用亚硝基二磺酸二钠盐更佳。
进行化合物(Ⅱ)的氧化是先将该化合物溶于诸如甲醇、乙醇、二氧杂环己烷、四氢呋喃等与水互溶的溶剂中,然后加入亚硝基二磺酸二碱金属盐。其加入量如按其与化合物(Ⅱ)的化学计量计算,应为其摩尔数的2.0倍,但考虑到亚硝基二磺酸二碱金属盐的稳定性,通常加入量为其摩尔数的2.6倍或更多,最好3.0倍或更多,反应温度在20°至70℃之间,以50℃左右最好。温度太低,反应速度太慢;反应温度太高亚硝基二磺酸二碱金属盐的分解加快,不希望有的副反应也容易发生,这是我们所不希望的。反应时间随起始化合物(Ⅰ)的浓度、所用的溶剂种类、亚硝基二磺酸二碱金属盐的用量以及反应温度等条件而变化,但通常一旦起始化合物消耗完毕,反应即停止。举例来说,用薄层色谱、高效液相色谱、气相色谱等方法跟踪,起始物料随时间减少,发现当起始物料不再被检出时,反应即终止。反应在50℃进行时,通常在两小时内即可完全。作为氧化剂的亚硝基二磺酸二碱金属盐的水溶液可通过电解羟胺二磺酸二碱金属盐的水溶液使之氧化而获得,电解可在一般化学电池中进行,化学电池可装有隔板或隔膜,通常以采用压力过滤器型装有阳离子交换膜的电化学电池最为可取,反应所放出的热可通过缩小电极间隙控制电池电压的升高、以及在电池外冷却高速循环于两电池室的阳极液和阴极液等方法来加以抑制。阳极和阴极可用任何通用于电化学领域的电极材料,如碳、铂、不锈钢、钯、镍、镍合金等。一般最乐于采用不锈钢网状电极。电解池可配上一搅拌装置,也可用泵加速反应液的循环。
进行电解氧化反应时可将羟胺二磺酸二碱金属盐的水溶液加以0.5至50伏的电压,以2至20伏为最适宜。通过溶液的电流密度可达每平方分米50安培。最好取用2至20安培。为使电解氧化反应的进行更有效,可在水溶液中加入常用的电解质,如氢氧化钠、醋酸钠、碳酸钠、碳酸氢钠、磷酸钠、氯化钠等。电解质的加入量一般相当于水溶液重量的0.1至30%。欲进行电解氧化反应的水溶液所含羟胺二磺酸二碱金属盐的浓度一般每升溶液至少含0.1摩尔,最佳范围是0.1至2摩尔。电解氧化反应的温度在-15°至50℃之间。一般以0°至35℃的范围最佳。反应时间至少0.5小时或更长,一般情况下反应应进行1至10小时。
电解氧化反应开始时,羟胺二磺酸二碱金属盐的水溶液pH值调在10与13之间,最好调在11.5左右,这样可使亚硝基二磺酸二碱金属盐的产量最高。
化合物(Ⅲ)能增强免疫力,有松弛肌肉的作用,还有能促使脑组织中酶的活化作用等。
本发明所用的起始化合物(Ⅰ)可以用一般的还原方法将以下述通式表示的化合物还原而得到:
式中符号所代表的意义同上。一般的还原方法有如利用锌汞齐和盐酸的Clemensen还原法、Wolff-Kishner腙还原法,二硫缩醛的脱硫还原法,或催化还原法。
本发明利用硼氢化钠和氯化铝的混合物将化合物(Ⅰ)还原,得到高产量的化合物(Ⅱ)。若于反应体系中加入水,欲得的化合物(Ⅱ)不但产量高、纯度高,且重现性也好。
本发明将以下实例和参考例作更进一步的详细说明。
参考例1
于9-(2-羟基-3,4-二甲氧基-6-甲基苯甲酰基)壬酸甲酯(2.0千克)的乙酸乙酯(10升)溶液中加入5%的钯碳黑(含水50%)(400克)和硫酸(10毫升)。混合物在30°至40℃通入氢气流(氢气压力约8.5千克/厘米2G)的条件下搅拌5小时。滤去催化剂,将乙酸乙酯层用水(10升)、用5%碳酸氢钠(10升)、再用水(10升)逐次洗涤。乙酸乙酯层经过浓缩后便可获得油状的10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸酸酯(1.8千克)产品。红外吸收光谱的λ薄膜 最大厘米-1为:3450(OH),1740(COOCH2)。核磁共振谱 为:1.10至1.87(14H,多重谱线,-(CH2)7-),2.17至2.57(4H,多重谱线,环CH2,CH2CO)、2.27(3H、单谱线,环CH2),3.63(3H,单谱线,COOCH2),3.80(3H,单谱线,OCH2),3.85(3H,单谱线,OCH2),5.80(1H,单谱线,OH),6.27(1H,单谱线,环H)
实例1
溶解10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸酸甲酯(881克,2.5摩尔)于1.8升四氢呋喃中。再在此溶液中加入硼氢化钠(340克、9摩尔)的四氢呋喃(10.7升)悬浮液,然后将此混合物搅拌。于所得的混合物悬浮液中加入水(75毫升,4.16摩尔),另将氯化铝(400克,3摩尔)溶解于四氢呋喃(6.0升)中。在90分钟内,以给定的速度将此溶液逐滴加至上述悬浮液中,在此期间反应物的内部温度应保持在25±2℃。然后,在相同的温度条件下再将反应物继续搅拌30分钟,并将之冷却至约15℃,往里逐滴加入水(22升),使发生分解反应,然后再逐滴加入盐酸(2.7升)。混合物用甲苯萃取两次,每次9升。合併两份甲苯层,先用碳酸氢钠(4.4升)的5%水溶液洗,再用水(4.4升)进一步洗涤,将甲苯层减压浓缩,便可得到10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1(805克,2.48摩尔,产率99.2%)的油状产品。红外吸收光谱ν净 最大cm-1为:3400(OH)左右。核磁共振谱为 :1.10至1.80(16H,多重谱线,-(CH2)8-,2.22(3H,单谱线,CH2),2.40至2.75(2H,多重谱线,CH2),8.50至8.70(2H,多重谱线,CH2),3.80(3H,单谱线,OCH2),8.84(3H,单谱线,OCH2),6.25(1H,单谱线,环H)。
实例2
对水的加入量与10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1的产量之间的关系进行了研究。将10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸羧甲酯(17.3克,49.1毫摩尔)溶于四氢呋喃(35.7毫升)中,加到硼氢化钠(6.8克,80毫摩尔)的四氢呋喃(214.5毫升)悬浮液中,搅拌此混合物。将准确量过(如表1所述)体积的水加到此悬浮液中。用四氢呋喃(142毫升)溶解氯化铝(8.0克,60毫摩尔)。将此溶液在内部温度为25±2℃条件下,在90至120分钟内逐滴加至上述悬浮液中。继续保持温度25±2℃,将反应物搅拌30分钟。然后将反应物冷却至15±2℃,并逐滴加入水(446毫升)。再缓慢地逐滴加入盐酸(53.5毫升),在此期间反应物的温度要求不超过20℃。接着反应物用甲苯萃取两次,每次178.5毫升。合併两份甲苯层,用水(89.5毫升)洗涤两次。把甲苯层减压浓缩,便可获得10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1的油状产物。表1示出所加入的水的体积与癸醇化合物的产率及所产生的二羟基化合物的量之间的关系。
表1 加入的水的体积与癸醇化合物的产率及所产生的二羟基化合物的量之间的关系
编号 | 加入的水的体积 | 癸醇化合物的产率(%) | 二羟基化合物的产率2)(%) | |
毫升数 | 摩尔比1) | |||
1234567891011121314 | 000.80.81.01.01.51.51.81.82.02.02.52.5 | 0.00.00.740.740.930.931.391.391.671.671.851.852.312.31 | 94.295.496.998.298.398.399.299.299.098.797.690.485.390.6 | 9.26.93.32.81.82.70.61.41.21.70.50.00.00.0 |
注1)
摩尔比= (加入的水的摩尔数)/(氯化铝摩尔数)
注2)
二羟基化合物的产率= (二羟化合物的峰面积)/(癸醇化合物的峰面积) ×100
二羟基化合物:10-(2,3-二羟基-4-甲氧基-6-甲基苯基)癸醇-1
参考例2
羟胺二磺酸二钠盐水溶液的合成
溶解亚硝酸钠(1875克)于水(7.5升)中,然后逐滴加入35%重量的亚硫酸氢钠水溶液(11.5升),同时保持溶液温度为0℃或更低。混合溶液中再逐滴加入醋酸(2,860毫升),同时使温度不超过5℃,在此温度条件下继续搅拌溶液90分钟。然后在10℃或更低温度下再逐滴加入30%重量的苛性钠水溶液(3,125毫升),再逐滴加入25%重量的碳酸钠水溶液(20升),便可获得能直接进行电解氧化的羟胺二磺酸二钠盐的水溶液。产量约为84%。
参考例3
用电解氧化反应合成亚硝基二磺酸二钠盐的水溶液。
单极、双室型和压力过滤器型的电化学电池(有效电极面积:4.5分米2/电池×2电池)中放入羟胺二磺酸二钠盐水溶液(6至8升)作为阳极液。碳酸钠的10%重量水溶液(6至8升)作为阴极液,再用泵使溶液进行循环。在给定的电解条件下(电流密度:8安/分米2,循环线性速度:10.4厘米/秒,温度:15℃)通电2至3小时,得到亚硝基二磺酸二钠的水溶液,产率为或大于90%。
参考例4-7
溶解10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1(271克)于甲醇(5.4升)中,于其中加入用电解氧化反应合成的亚硝基二磺酸二钠的水溶液(6.7升,浓度为0.359摩尔/升),保持温度在50±2℃,搅拌此混合溶液2小时。用薄层色谱法证实起始物料已告消失后,反应混合物中加入水(8.6升),继用甲苯萃取二次(5.5升及2.7升)。合併二次甲苯萃取液,用水洗涤。进行减压浓缩:得6-(10-羟基癸基)-2,3-二甲氧基-5-甲基-1,4-苯醌粗品(288克,含量94.8%、产率96.9%)。粗品(20克)从甲苯(60毫升)与正己烷(180毫升)混合溶剂中重结晶。结晶用甲苯(60毫升)溶解,并使此溶液通过活性氧化铝(30克)涂层。减压浓缩此流出液,浓缩液再从甲苯(55毫升)与正己烷(165毫升)的混合液中重结晶一次。又从50%乙醇(108毫升)中进一步重结晶。干燥后得到16.2克橙黄色的6-(10-羟基癸基)-2,3-二甲氧基-5-甲基-1,4-苯醌结晶,熔点54.0℃。
红外吸收光谱:νKBr 最大厘米-1:3550(OH),1660,1650,1610(1,4-苯醌)
核磁共振谱 :1.1至1.8(16H,多重谱线,-(CH2)8-),2.00(3H,单谱线,CH2),2.43(2H,三重谱线,J=7Hz,CH2),3.63(2H,三重谱线,J=6Hz,CH2OH),3.97(6H,单谱线,OCH2)
用通过电解氧化反应合成的亚硝基二磺酸二钠水溶液的各种实例均列述于表2
表2 用通过电解氧化反应制备的亚硝基二磺酸二钠水溶液进行1的氧化
实例编号 | 加入量 | 反应条件 | |
OH3OH(克)(摩尔/升)(升) | 温度 时间(℃) (小时) | 产量 产率(克) (%) | |
4567 | 271 2.41/6.7 5.4262 2.32/6.7 5.2308 2.96/7.6 6.1372 3.40/7.6 7.6 | 48-53 2.048-53 2.048-52 2.048-50 2.0 | 273 96.9266 97.3318 98.9380 98.0 |
参考例8-10
将10-(2-羟基-3,4-二甲氧基-6-甲基苯基)癸醇-1(6.84千克)溶于甲醇(110升)中,于其中加入醋酸钠(27.4千克)与水(110升)。往此混合物中加入亚硝基二磺酸二钾盐(23.5千克,含量69.9%),混合液在温度50±3℃下搅拌3小时。用薄层色谱法检查证实起始物料消失后,加入水(550升),在或低于10℃下搅拌30分钟或更长,离心分离析出的结晶。收集结晶,溶于乙酸乙酯(40升)中,用水(25升)洗涤。减压浓缩乙酸乙酯层,得到6-(10-羟基癸基)-2,3-二甲氧基-5-甲基-1,4-苯醌粗品(6.70千克,产率93.9%)。采用亚硝基二磺酸二钾盐(Fremy盐)的实例均列于表3。
实例3
将6-(2-羟基-3,4-二甲氧基-6-甲基苯基)己酸甲酯(7.41g,25mmol)溶于四氢呋喃(18ml)中。再将硼氢化钠(3.40g,90mmol)在四氢呋喃(11ml)中的悬浮液加到上述溶液中,搅拌此混合物。将水(0.75ml,41.6mmol)加到搅拌所得的悬浮液中。另将氯化铝(4.00g,30mmol)溶于四氢呋喃(60ml)中。再将此溶液在90分钟内以一定的速率滴加到上述悬浮液中。在此期间将该反应混合物的内部温度保持在25±2℃。然后,将反应混合物在同一温度再搅拌30分钟,然后冷却至约15℃。将水(220ml)逐滴加到上述反应混合物中以引起分解作用,然后再将盐酸(27ml)逐滴加到反应混合物中。用甲苯萃取该混合物两次,每次用90ml甲苯。然后将甲苯层合并,并用5%碳酸氢钠水溶液(44ml)洗涤甲苯层,接着再用水(44ml)进一步洗涤。在减压下浓缩甲苯层而得到6-(6-羟基己基)-2,3-二甲氧基-5-甲基苯酚(6.44g,24mmol,96.0%)是一种油状物。
红外线吸收谱λfilm maxcm-1:3450(OH),1610,1580(苯基)
核磁共振谱δCDCl ppm3:1.10 to 1.80(8H,多重线谱,-(CH2)4-),2.23(3H,单一线谱,C5-CH3),2.73(2H,三重线谱,J=7Hz,C1-H2),3.61(2H,三重线谱,J=6Hz,-CH2OH),3.80(3H,单一线谱,OCH3),3.84(3H,单一线谱,OCH3),5.82(1H,单一线谱,C1-OH),6.24(1H,单一线谱,C4-H).
实例4
将20-(2-羟基-3,4-二甲氧基-6-甲基苯基)二十碳烷酸甲酯(12.32g,25mmol)溶在四氢呋喃(25ml)中,再将硼氢化钠(3.40g,90mmol)在四氢呋喃(11ml)中的悬浮液加到此溶液中,并搅拌此混合物。再将水(0.75ml,41.6mmol)加到所形成的悬浮液中。另将氯化铝(4.00g,30mmol)溶于四氢呋喃(60ml)中。以一定的速率用90分钟将此溶液滴加到上述的悬浮液中,在此期间反应混合物的内部温度保持在25±2℃。然后,在此温度再将反应混合物搅拌30分钟,之后再将反应混合物冷却至约15℃。将水(220ml)逐滴加到反应混合物中以引起分解作用。再向溶液中逐滴加入盐酸(27ml)。用甲苯萃取该混合物两次每次用90ml甲苯。然后合并该甲苯层并用5%碳酸氢钠水溶液(44ml)洗涤。在减压下浓缩该甲苯层而得到6-(20-羟基二十碳烷基)-2,3-二甲氧基-5-甲基苯酚(10.80g,23.2mmol,92.9%),熔点72℃(在乙醚中重结晶)。
红外线吸收谱λKBr maxcm-1:3450(OH),3150(OH),1580(苯基)。
核磁共振谱δCDCl ppm3:1.10 to 1.90(36H,多重线谱,-(CH2)18-),2.23(3H,单一线谱,C5-CH3),2.54(2H,三重线谱,J=7Hz,C1-H2)3.61(2H,三重线谱,J=6Hz,CH2-OH),3.80(3H,单一线谱,OCH3),3.83(3H,单一线谱,OCH3),5.80(1H,单一线谱,C1-OH)and 6.25(1H,单一线谱,C4-H).
实例5
将6-(6-羟基己基)-2,3-二甲氧基-5-甲基苯酚(2.15g,8mmol)溶于甲醇(50ml)中,在此溶液中加入用电解氧化作用的方法合成的亚硝基二磺酸二钠的水溶液(60ml,含0.402mol/l)。将此混合物搅拌两小时并保持温度在50±2℃。在用薄层色谱法确认起始物质已消失之后,将水(90ml)加到反应混合物中,接着两次用甲苯(50ml和25ml)萃取。将甲苯层合并并用水(50ml×2)洗涤。在减压下浓缩甲苯层以得到6-(6-羟基己基)-2,3-二甲氧基-5-甲基-1,4-苯醌(2.10g,93.0%),是一种油状产物。
红外线吸收谱λfilm maxcm-1:3400(OH),1660,1640,1610(1,4-苯醌)
核磁共振谱δCDCl ppm3:1.20 to 1.80(8H,多重线谱,-(CH2)4-),2.01(3H,单一线谱,C5-CH3),2.45(2H,三重线谱,J=7Hz,C1-H2),3.62(2H,三重线谱,J=6Hz,-CH2OH),3.98(6H,单一线谱,OCH3x2).
实例6
将6-(20-羟基二十碳烷基)-2,3-二甲氧基-5-甲基苯酚(3.72g,8mmol)溶于甲醇(60ml)中,在此溶液中加入用电解氧化作用的方法合成的亚硝基二磺酸二钠的水溶液(63ml,含0.385mol/l)。将此混合物搅拌两小时同时将温度保持在50±2℃。在用薄层色谱法确认起始物质已消失之后,将水(90ml)加到反应混合物中,接着用甲苯(50ml和25ml)萃取两次。合并甲苯层并用水(50ml×2)洗涤、在减压下浓缩甲苯层而得到6-(20-羟基二十碳烷基)-2,3-二甲氧基-5-甲基-1,4-醌酯(3.61g,94.3%),是一种黄色结晶,熔点85℃(用乙醚重结晶)
红外线吸收谱λKBr maxcm-1:3550(OH),1650,1640,1610(1,4-苯醌)
核磁共振谱δCDCl ppm3:1.10 to 1.80(36H,多重线谱,-(CH2)18-),2.00(3H,单一线谱,C5-CH3),2.43(2H,多重线谱,J=7Hz,C1-H2),3.62(2H,三重线谱,J=6Hz,-CH2OH),3.96(6H,单一线谱,OCH3x2).
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