羧酸酯一般來說較易被還原伯醇，其常用的方法為金屬鈉和醇Na-EtOH；金屬氫化物如氫化鋁鋰(LAH), 硼氫化鈉（鉀）等。其中金屬氫化物是最為常用的還原劑。
金屬鈉和醇為還原劑（Bouveault-Blanc反應(yīng)）
本反應(yīng)是將羧酸酯用金屬鈉和無水醇直接還原生成相應(yīng)地伯醇，主要用于高級(jí)脂肪羧酯的還原。
由于催化氫化和氫化鋁鋰的廣泛應(yīng)用，此法在實(shí)驗(yàn)室中已經(jīng)很少采用，但是因?yàn)槠浜?jiǎn)便易行，在工業(yè)上仍然廣泛應(yīng)用。Bouveault-Blanc反應(yīng)的歷程可能如下：
反應(yīng)實(shí)例
一、金屬鈉和醇為還原劑（Bouveault-Blanc反應(yīng)）示例
The central neck of a 5-l. three-necked round-bottomed flask is fitted with astopper carrying a mercury-sealed mechanical stirrer. One of the side necks isconnected by means of a short piece of heavy rubber tubing to a large refluxcondenser about 2 m. long, with an inner tube 2.5 cm. in diameter. The thirdneck is fitted with a separatory funnel.
In the flask are placed 70 g. (3 moles) of sodium and200 cc. of dry toluene. The flask is heated in an oil bath until the sodium ismelted. The stirrer is then started; when the sodium is finely divided, the oilbath is removed and the mixture allowed to cool. Stirring must be continuedduring the cooling in order to keep the sodium finely divided.
Whenthe mixture has cooled to about 60°, there are added from the separatoryfunnel, first, a solution of 114 g. (0.5 mole) of ethyl laurate in 150 cc. ofabsolute alcohol, then 500 cc. more of alcohol, as rapidly as is possiblewithout loss of material through the condenser. The time required for theaddition of the ester solution and the alcohol is less than five minutes,usually two or three minutes. When the reaction has subsided, the flask isheated on a steam bath until the sodium is completely dissolved. The mixture isthen steam-distilled to remove the toluene and ethyl alcohol. The contents ofthe flask are transferred to a separatory funnel while still hot and washedthree times with 200-cc. portions of hot water to remove the sodium laurate.The lauryl alcohol is extracted with ether from the cooled mixture and thewashings. The combined ether extracts are washed with water, sodium carbonatesolution, and again with water, and dried over anhydrous magnesium sulfate. Theether is evaporated and the lauryl alcohol distilled under diminished pressure.The yield is 60–70 g. (65–75 per cent of the theoretical amount) of a productboiling at 143–146°/18 mm. or 198–200°/135 mm.
【Organic Syntheses, Coll. Vol. 2,p.372; Vol. 10, p.62.】
金屬氫化物為還原劑
羧酸酯用0.5 mol的氫化鋁鋰還原時(shí)，可得到伯醇。
如僅用0.25mol并在低溫下或降低氫化鋁鋰的還原能力，可使反應(yīng)停留在醛的階段。
降低氫化鋁鋰還原能力可以提高還原反應(yīng)的選擇性。常用的的方法是加入不同比例的無水三氯化鋁或者加入計(jì)算量的醇，取代氫化鋁鋰中1-3個(gè)氫原子而成鋁烷、或烷氧基氫化鋁鋰。如用烷氧基氫化鋁鋰還原α,β-不飽和酯到α,β-不飽和醇，若單用氫化鋁鋰還原，則得到飽和醇。
單純使用氫化硼納納還原酯效果較差，若在Lewis酸如AlCl3, ZnCl2存在下，還原能力大增，可順利的還酯，甚至可還原某些羧酸。
由氫硼化鈉和?；桨吩讦?甲基吡啶中反應(yīng)，生成的酰苯胺氫硼化鈉是還原酯的有效試劑。其優(yōu)點(diǎn)：反應(yīng)操作簡(jiǎn)便，不需要無水條件，反應(yīng)選擇性好。
一、 LAH還原羧酸酯成伯醇示例
利用LAH還原羧酸酯到伯醇是一個(gè)快速，后處理較為簡(jiǎn)便的方法，一般情況下，酯基可在零下30℃下反應(yīng)30 分鐘即可被還原。因此即使分子內(nèi)有酰胺或其他一些敏感的官能基存在也沒什么關(guān)系。
A dry, 500-mL, three-necked, round-bottomed flask isequipped with a 150-mL pressure-equalizing addition funnel, a reflux condensertopped with an inert atmosphere line, a glass stopper, and an egg-shapedmagnetic stirring bar. The flask is charged with lithium aluminum hydride (2.66g, 0.070 mol) and anhydrous ether (50 mL). The flask is cooled to 5°C in anice-water bath. A solution of (2R)-methyl4-(tert-butyldimethylsilyloxy)-2-(dimethylamino)cyclohex-3-enecarboxylate (22.4g, 0.072 mol) in ether (80 mL) is transferred to the addition funnel and addedover a 30-min period. The reaction mixture is stirred for another 15 min,diluted with ether (100 mL), and quenched by dropwise addition of water (9 mL).The ice-water bath is removed, the resulting gray suspension is allowed toreach room temperature, and the mixture is stirred vigorously for an additional60 min. The mixture is transferred to a 1.0-L Erlenmeyer flask and diluted with350 mL of ether. Anhydrous sodium sulfate (Na2SO4) (60 g) is added,the suspension is stirred for 30 min, and filtered. The filter cake is washedtwice with ether (50 mL each time). The solvent is removed on a rotaryevaporator and the remaining volatile material is removed under high vacuum toafford 18.6 g (91%) of ((2S)-4-(tert-butyldimethylsilyloxy)-2-(dimethylamino)cyclohex-3-enyl)methanolas a viscous clear oil.
【Organic Syntheses, Coll. Vol. 10, p.442; Vol. 78, p.160.】
二、異丁醇鋁還原α,β-不飽和酯到α,β-不飽和醇示例
To a solution of3-(1H-benzoimidazol-5-yl)-acrylic acid methyl ester (50 mg in 1 ML drytetrahydrofuran) at -78.deg. C. was added 1.24 NL of a 1M solution of lithiumtri-sec-butylborohydride in tetrahydrofuran and the mixture stirred at -78.deg.C. for 4 hours followed by warming to -40.deg. C. for an additional 4 hours.
Thereaction was quenched by addition of aqueous methanol, concentrated in vacuoand purified by flash chromatography on silica gel (methylenechloride:methanol, 87:13) to give the title compound (44 mg).
【 (Patent; Merck and Co., Inc.;Publ.: US5849764 A1 (1998/12/15), Appl.: US1996-760817 (1996/12/05))】
三、硼氫化鈉（鉀）還原羧酸酯成伯醇示例
利用硼氫化鈉（鉀）還原羧酸酯到伯醇操作較為安全，簡(jiǎn)單的方法，由于硼氫化鈉的還原性不夠強(qiáng)，因此這類反應(yīng)一般需要回流過夜。反應(yīng)初始階段不要去加熱，而是在室溫下攪拌數(shù)小時(shí)后在，再加熱緩緩回流，否則反應(yīng)極容易噴出來。硼氫化鈉在甲醇中分解較快，這個(gè)反應(yīng)盡量不要用甲醇做溶劑。
To a stirred suspension of 58.5g (300mmol) of dimethyl pyridine-2, 6-dicarboxylatein 800ml of anhydrous ethanol was added in portions 53.0g (1400mmol) of sodiumborohydride at 0°C, after stirring for 1h at 0°C, the ice bath was removed andthe ongoing exothermic reaction caused the solution to boil under reflux.Stirring was continued for 3h, then the solution was heated under reflux foranother 10h. The solvent was distilled off and the residue was digested with200ml of acetone. The acetone was distilled off; to the residue was added 200mlof a saturated aqueous solution of K2CO3 and the wholewas heated for 1h with a boiling water bath. The solvent was again distilledoff, the residue was dissolved in 800ml of water, and sodium chloride was addedin portions with stirring until a colorless precipitate was formed. The productwas extracted three times, each time with 150ml of chloroform, the combinedorganic phases were dried with MgSO4 and filtered. The solvent wasdistilled off to give 37.8g (91%)of desired product as colorless needles。
【Liebigs Ann.lRecueil 1997,707-720.】
四、NaBH4-ZnCl2還原酯示例
To a suspensionof ZnCl2 (80.36 g, 0.591 mol) in dry THF (1000 mL), NaBH4(11.2 g, 0.3043 mol) was added in portions at 0~5℃ under nitrogen. Themixture was stirred for 30 min at 20~25 ℃, The mixture was cooledto 0~5 ℃ and compound (S)-diethyl 2-(triisopropylsilyloxy)succinate(82 g, 0.2368 mol) was added dropwise at 0~5 ℃. Then the mixture waswarmed to 55~60 ℃ and stirred for 18 hours. Afterconfirming the completion of reaction by HPLC, The result reaction mixture was cooledto -15~-10 ℃. Water (213 mL) was added dropwise to quench the reaction at-15~-10 ℃. The reaction was aged for 3 h at 20~25 ℃.Charged celite (12.3 g) to the mixture and then the solid was removed byfiltration. The filtrate was concentrated under vacuum to remove THF. And thefilter cake was washed with CH2Cl2 (250×3mL). The combined organic layers were washed with water (200 mL) and themixture was separated and the organic layer was dried over Na2SO4.The solution was concentrated to give compound (S)-2-(triisopropylsilyloxy)butane-1,4-diol (44.68 g, 0.170 mol, yield 71.9%).
【Organic Syntheses, Coll. Vol. 7, p.530; Vol.63, p.136.】
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