DAEHAN HWAHAK HW야 JEE , @ 、 (Journal of the Korean Chemical Society； VoL 15, Number 3, 1971 Printed in Republic of Korea Two Phase Reduction of Carbonyl Compounds with Sodium Borohydride Jin Soon Chong* and Nung Min Yoon** • Department of Chemistry, Chon-Nam University, Kwang-Ju, Korea. **Department of Chemistry, Sogang University, Seoul. Korea. (Received Jan. 18, 1971) Abstract Possibility of two phase reduction of carbonyl compounds to the corresponding alcohols was studied. Thus the 0.5 M ether solutions of the representative carbonyl compounds were treated with alkaEne stebilized sodium borohydride aqueous solution at room temperature. Butyraldehyde was reduced rapidly within one 뇨 whereas other aldehydes tested; heptaldehyde, benzaldehyde, and l-naphthaldehyde were reduced in 6-12 hr. 2-Heptanone was reduced much slowly 87% in 48 hr., however, acetophenone was reduced moderately; 92% in 12 hr. and cycloalkanones were reduced rapidly (cyclohexanone in 0.5 hr., and cyclopentanone in 3-6 hr.). dation of secondary alcohols to ke仅me조 ， 4 Therefore we studied the possibilty of th혀 Introduction two phase reduction of carbonyl compound요 in ether with alkaline stabilized aqueous sodium Unlike a strong reducing agent, lithium alumi­ borohydride solution, in order to overcome th흔 num hydride, sodium borohydride is a mild possible difficulties due to the solvent for the reducing agent, and has been used extensively sodium borohydride reduction. for the various kinds of selective reduction.半 However, sodium borohydride is insoluble in Experimental ether and tetrahydrofuran, more common advents for organic compounds, whereas lithium alumi­ num hydride is readily s시 u비 e in these solvente. Materials. All the carbonyl compounds and Therefore it is customary to use such solvents the glpc stand&ids used were checked for their as methanol, ethanol, isopropyl alcohol, pyridine, purity by their refractive index. The commercial alkaline water, and diglyme for the reduction sodium borohydride(Ventron) was used without with sodium borohydride. Alth이 】횽 h diglyme 허 s・ further purification. Analysis by hydrogen evo­ solves the hydride moderately, its reducing lution measurement on hydr시 ysis showed 98% ability was found to be significandy changed.8 purity. On the other hand, Brown and Garg reported General procedure for two phase reduction a convenient two phase reduction for the oxi­ —117 一 118 Jm Soon Chong and Nung Min Yoon The two phase reduction of heptaldehyde is dride present in ether layer. And the whole •described as a representative of the procedure. aqueous layer was hydrolyzed after the reaction, In a 100 ml. flask, fitted with an inlet tube, a extracted with ether, and glpc analysis show* magnetic stirrer and a reflux condenser thro­ ed no heptyl alcohol in this aqueous layer. ugh which a gas meter is connected, there was placed a 15 ml. of 0.25 M sodium borohydride Two phase reduction of 1-naphthald* solution in 0.25 M NaOH aqueous solution (3. ehyde on a preparative scale. In a 300 ml. 75 mmoles NaBH^, that is 15 mmoles hydride), round bottom flask, fitted with a magnetic A 20 ml. of 0.5 M heptaldehyde solution in stirrer, and an inlet tube, there was placed ether, which is also 0.5 M in mesitylene added a 0.72 g. of sodium borohydride (18.75 as an internal standard for the glpc analysis was mmoles) dissolved in 75 ml. of 0.25 M NaOH added at a time while the solution was moder­ solution. A 7.81 g. of 1-naphthaldehyde (50 ately stirred. After Ihr., 2ml. of the ether layer mmoles) dissolved in 100 ml. of ether was add­ was taken out and analyzed for heptaldehyde and ed at a time while the $이 ution was moderately heptyl alcohol using Carbowax 20M column, with stirred. After 6 hr. at room temperature, the F&M 720. Analysis showed 52% yield of heptyl ether layer was separated without prior hydro­ alcohol and 45.2% of heptaldehyde remained. lysis and dried over anhydrous magnesium sul­ These estimation was made by area measure­ fate, and the ether was evaporated away by ments, and the retention time of heptaldehyde distillation. The residue was dried completely and heptyl alcohol were 2.4min. and 7. Imin., under reduced pressure, and there was obtained using 6 feet of 1/4 inch Carbowax 20M column, a 7.5 g. of crude 1-naphthyl-methanol (95%). at 140 °C. with flow rate of 57 ml. /min. The This was dissolved in 20 ml. of a mixture of 2 ml. aliquots were also taken out at 3,6 and ether and ethanol (1：1 v/v)and left in the open 12 hr., and the glpc analysis showed 88, 97, air. On the gradual evaporation of the solvent, and 100% yields of heptyl alcohol respectively. 7.27 g. of 효 needle crystal of 1-naphthyl-methan­ In the case of 1-naphthaldehyde, the reaction ol (92% yie너 ), m.p. 59.5°C(lit5., 60°C) was could not be followed by glpc analysis, therefore obtained. the 2 ml. aliquots of the ether layer were added to 2,4-dinitrophenylhydrazine solution. There Resalts and Discussion was no precipitate of 2,4서 initrophenylhydr* ^one after 6 hr,, indicating the completion of First, we tested the possibility of the two the reduction. The absence of aldehyde was phase reduction with heptaldehyde, and follow­ also checked by I, R. ed the reaction with the formation of heptanol by glpc. The results are summerized in Table 1. As shown in entry 1, when 10 mmoles of Tests for the distribution of hydride and the aldehyde in 20 ml. of ether was treated alcohol in two phases. The 4 ml. of the with 2 5 mmoles (고 0 mmoles of hydrides) of •ether layer w효 $ hydrolyzed with 2 N sulfuric sodium borohydride in 20ml. of 0.1 M sodium wcid solution, in order to find out any hydri- hydroxide solution, the reaction slowed down de in ether layer. There was no hydrogen considerably after 3 hr., and there was practi­ -evolution observed, showing no active hy­ cally no hydride left after 12 hr. Apparendy Journal of the Korean Chemical Society Two Phase Reduction of Carbonyl Compounds with Sodium Borohydride 119 o. 1 M NaOH solution is not sta이 e enough very slowly; 87.7% in 48 hr., but acetophenone was faster about four times than 2~heptanone for our purposes. Therefore we added 2.5 m- 92% in 12hr. Cyclic ketones were reduced much m 시 es of the hydride in 10 ml. of 0.25 M NaOH faster than 2-heptanone or acetophenone. Thus (entry 2). The solution became more stable and cyclopentanone was reduced in 3-6 hr. a서 cycl­ the rate of reaction also increased, however, ohexanone was rapi키 y reduced within 1 hr. the observed result, 91% yield in 12 hr. was felt inadequate for practical purposes. The more Table 2. Two Phase Reduction of Representative faster reaction was realized by adding 15 mm시 es Carbonyl Compounds in Ether with Aqueous of fydride" (50% excess) in 15 ml. of 0.25 Sodium Borohydride at Room Temperature. M NaOH solution (entry 3・). Thus it was proved that the aldehyde in its 0.5 M con cent- Compound0 Reduction, * hr. 48.0 ratica in ether could be reduced in 6-12 hr. 1.0 3.0 6.0 12.0 。시 at room temperature, using y 50% excess of Butyraldehyde 100 the 城 &너 e. Heptaldehyde 52 88 97 100 Benzaldehyde 78 95 98 100(8" Tabb 1. Two Phase Reduction of Heptaldehyde 1-Na 호 hthaldehyde 100K92)。 at Room Temperature. 2-Heptanone 9 18 20 87.7 68 92 申 卩单너 * NaBH4 Reduction, a hr. Acetophenone 32 52 Entry ehyde Mmole 1.0 3.0 6. 0 12- 0 Cyclopentanone 88 92 100 Mmole ______________ ___ ______ __________ Cyclohexanone 100(90)。 1. 104 2. 5(dissolved in 20 27 62 67 71 ml. of 0.10M NaOH) a. 10 mmoles of each carbonyl compound(20 ml. of 2. 10J 2. 5(dissolved in 10 33 65 81 91 0.5 M ether solution) was reduced with 3.75 ml. of 0. 25M NaOH) mm이 es of sodium borohydride which was dis­ 어 이 3. 3. 75 iss ved in 15 52 88 97 100 solved in 15 ml. of 0.25 M sodium hydroxide ml. of 0.25M NaOH) solution. b. % of reduction estimated by glpc analysis of the a. % of reduction estimated by analysis of hetyl- corresponding alcohols. alcohol c. % of yield, estimated by the isolation of the b. 20 ml. of 0- 5 M glution. product. d. The completion of the reaction was checked by The reaction time is a li비 e longer, but the the absence of 2,4-dinitrophenylhydrazone 50% excess is a good economy when compared to the large excess comm。이 y used in hydroxylic The rates of reduction of these ketones are 몹 solvents. Therefore we applied this method to parallel to those in isopropyl alcohol preview ly the four aldehydes and four ketones. The res니 ts studied. 6»7 Another points of interest are, whe- are summarized in table 2. Butyraldehyde was thei the product alcohols distribute in ether and reduced rapi히 y within one hr., whereas the aqueous layer, either free or alkylborate forms, .other aldehyde tested, heptaldehyde, benzalde­ and are there any active hydride in ether layer. We confirmed that there is practically no 효 1c 사 0 hyde, and 1-naphthaldehyde were all completed in. water layer and no hydride in ether layer. in 6-12 hr., Apparently the water solubility of We believe this makes the two phase reduction butyraldehyde is responsible to the fast reaction.