DAEHAN HWAHAK HWOEJEE (.Journal of the Korean Chemical Society) Vol. 27, No. 1. 1983 Printed in the Republic of Korea 수소화 붕소리튬을 이용한 다중작용기를 가진 화합물에서 할라이드의 선택환원 趙炳泰•尹能民十 서강대학교 이공대학 화학과 (1982. 8. 9 접수) Selective Reduction of Halides with Lithium Borohydride in the Multifunctional Compounds Byung Tae Cho and Nung Min Yoont Department of Chemistry, Sogang University, Seoul 121, Korea, (Received Aug. 9, 1982) 요 약. 한 분자내에 클로로, 니르로, 에스테르 및 니트릴기를 포함하는 할로겐 화합물에서 수소 화붕소리튬을 이용한 할로겐의 선택환원이 논의되었다. 브로모-4-클로로부탄은 96 %의 수득율로 I-클로로부탄으로, 브롬화 />-니트로벤질은 98 %의 수득율로 A니트로 톨루엔으로 환원되었으나 요 오도프로피온산 에 틸에스테르나4-브로모부티로니트릴의 경우 선택 환원의 수득율이 낮았다. 그러나 당 량의 피리딘 존재하에서 이 반응을 시키면 프로피온산 에틸에스테르는 93%, 부티로니트릴은 88% 로서 각각 선택환원의 수득율이 향상되었다. ABSTRACT. Selective reduction of halide (Br, I ) with lithium borohydride in halogen com­ pounds containing chloro, nitro, ester and nitrile groups was achieved satisfactorily, l-bromo-4- chlorobutane was reduced to 1-chlorobutane in 96% yield and the reduction of y)-nitrobenzyl bro­ mide gave />~nitrotoluene in 98 % yield. However, the selectivity on the reduction of ethyl 3- iodopropionate and 4-bromobutyronitrile required the presence of equimolar pyridine to give good yields of ethyl propionate (93 %) and w-butyronitrile (88 %), respectively. In ^competitive reduc­ tion of 1-bromoheptane and 2-bromoheptane, lithium borohydride reduced 1-bromoheptane pre­ ferentially in the molar ratio of 93： 7. and secondary iodides, bromides, chlorides). INTRODUCTION On the other hand, it was also realized that It was reported that both lithium aluminum remark사)ly mild reducing agents, sodium boro­ hydride and lithium triethylborohydride exhi­ hydride and sodium cyanoborohydride reduced bited exceptional utility for the reduction of successfully alkyl halides in dimethyl sulfoxide alkyl halides and tosylates.1,2 However, they or hexamethyl phosphoramide. However, way be inadequate for selective reduction of they reduced smoothly both alkyl bromides and halides in the multifunctional compounds, since alkyl chlorides (for example, with both 2 equiv. they are powerful reducing agents, capable of sodium borohydride in dimethyl sulfoxide at reducing many functional groups, such as ester, 85°, 95 % reduction of l-bromododecane in nitrile, nitro and all kinds of halides (primary L5h and 91 % reduction of 1-chlorododecane —4 6 — 수스화 붕소리튬을 이용한 다중작용기를 가긴 화합문이서 할가이上升 선니관긴 47 in 4 h4) It is difficult to expect selective products were determined by utilizing suitable reduction of bromide with these reducing internal standards and authentic mixtures. The agents in the presence of chloride. following columns were used: 10 % carbowax Recently it was reported that lithium boro- 20 M on chromosorb WHP, 6 ft, 0.125 inch hydride reduced alkyl iodides and alkyl bromi­ (Column A), 10 % OV-17 on chromosorb des in moderate yields in tetrahydrofuran at WHP, 6 ft, 0-125 inch (Column B) and 10 % room temperature, whereas alkyl chlorides were OV-1 on chromosorb AVHP, 6 ft, 0.125 inch. essentially inert to lithium borohydride under (Column C) the same conditions.2*7 And it was found that Lithium Borohydride Solution in Tetrahy­ lithium borohydride was a mild reducing agent drofuran. A 250 mZ, oven-dried flask, equip­ which could reduce readily only few organic ped with a side arm, httccl with a silcon rub­ functional groups such as aldehydes, ketones ber cap, and a magnetic stirring bar, was and acyl chlorides at room temperature. There­ cooled down to room temperature under a dry fore, we decided to examine selective reduction stream of nitrogen. In the flask were placed of bromide and iodide with lithium borohydride 6. 37 g (98 %, 165 mmol) of finely divided so­ in compounds containing the other functional dium borohydride and 6. 3885 g (150 mmol) of groups, such as chloride, nitro, ester and nitrile lithium chloride. Then, the fiask was fitted groups, less susceptible to this reducing agent. with a reflux condenser connected to a mercury bubbler and heated at about 150° for ih with EXPERIMENTAL stirring under a stream of nitrogen. Thereafter, General. All glasswares were thoroughly the flask was cooled down to room temperature dried in a drying oven and cooled down under under a dry stream of nitrogen, and 160 mZ of a stream of dry nitrogen just prior to use. distilled THF was introduced to provide a solu­ Most of the organic compounds utilized in tion of about 1.0 M in lithium borohydride, 4 this study were commercial products of the M in hydride. The flask was heated at a rate highest purity. They were further purified by sufficient to maintain a gentle reflux for 5 days distillation or recrystallization when necessary. with continuous stirring. After 5 days, the Sodium borohydride (98 % Aldrich Chem： Co) solution was cooled down to room temperature was used without further purification, but dried under a dry stream of nitrogen, and allowed out in a heating vacuum oven at 120° for 12 h. to stand to permit sodium chloride and unreac­ All of the solvents used were dried with ted sodium borohydride to settle down. The excess lithium aluminum hydride, distilled un­ upper solution was stored under dry nitrogen der nitrogen, and stored over 4 A molecular in a 250 m/ flask with a side arm, closed with sieve in a flask equipped with a rubber septum a rubber cap for removing aliquots. The solu­ inlet and a connection to a mercury bubbler. tion was standardized by removing a known All reduction experiments were carried out aliquot with a hypodermic syringe, hydrolyzing under a dry nitrogen atmosphere. Hypodermic with a THF-water-2 N sulfuric acid (1 : 1 : 1) syringes were used to transfer the solution. mixture and measuring the hydrogen evolved. Glpc analysis was performed on Hewlett Pac­ The concentration was found to be 0.91 M solu­ kard Model 5840 A instrument equipped with tion of lithium borohydride in THF. flame ionization detector. All of the yields of Reaction of Aik미 Halides with Lithium Vol. 27, No. 1, 1983 48 趙炳泰•尹能民 Borohydride in THF at Room Temperature n-dodecane in THF to serve as an internal or at 65°. The reduction of n-heptyl iodide standard were introduced into a reaction flask. at 65° is described as a representative. A clean And then 10 mZ(10 mmol) of 1.0 M solution of 100 mZ, oven-dried flask with a side arm, fitted l-bromo-4-chlorobutane in THF was added. with a silicon rubber cap, a magnetic stirring The reaction mixtures were heated to reflux. bar, and a reflux condenser connected to a mer- After 18 h, g Ipc analysis on column C indica­ cury bubbler, was cooled down to room tempe­ ted the formation of 96 % 1-chlorobutane. rature under a stream of dry nitrogen. Then (Table 2) 9 mZ of THF was introduced into the flask by Selective Reduction of Bromide in the Pre­ a hypodermic syringe, followed by 11 mZ (10 sence of Nitro Group with Lithium Boro­ mmol) of a 0.91 -A/ THF solution of lithium hydride. The reduction of /»-nitrobenzyl bro­ borohydride and 5 mZ (5 mmol) of a 1.0 AZ THF mide was carried out as a representative. The solution of toluene and 5 ml (5 mmol) of a 1. 0 experimental set-up and work-up procedure for M THF solution of dodecane to serve as inter­ analysis of the product were performed as desc­ nal standards. Finally, 10 mZ (10 mmol) of 131 ribed in the previous experiments. Into a 100 THF solution of n-heptyl iodide was added. mZ flask, 9 ml of THF, 11 mZ (10 mmol) of The mixture was heated to reflux in an oil 0.91 M THF solution of lithium borohydride bath. At appropriate intervals of time, 1 mZ of and 10 mZ (5 mmol) of 0.5 M solution of di­ the reaction mixture was withdrawn by a hypo­ phenyl ether in THF to serve as an internal dermic syringe, quenched with 1 mZ of 1 M sul­ standard were introduced. Finally, 10 mZ (10 furic acid, saturated with anhydrous potassium mmol) of 1. 0 M />-nitrobenzyl bromide solution carbonate and extracted with 2 mZ of ether, in THF was added. and the upper layer was checked by glpc analysis The reaction mixtures were maintained at using a column C. At 1 h, glpc analysis indi­ room temperature. After 3 h, glpc analysis cated that n-heptane was formed in the yield using column C revealed the presence of 98 % of 92 % and 8 % M-hepthyl iodide remained. />-nitrotoluene. (Table 2) The results were summarized in Table 1. In Selective Reduction of Iodide in the Pre­ all cases of incomplete reduction for 24 h, the sence of Ester Group with Lithium Borohy­ reaction mixture were oxidized and worked up dride. The following procedure for the reduc­ as a usual procedure. Glpc examination reveakd tion of ethyl 3-iodopropionate was carried out as the complete absence of heptanols. Starting a representative. The experimental set-up was materials were recovered. the same in the previ이is experiments. 4 mZ of Selective Redution of Bromide in the Pre­ THF was introduced into the reaction flask by sence of Chloride with Lithium Borohydride. a hypodermic syringe, followed by 5 mZ (10 The reduction of l-bromo-4-chIorobutane was mmol) of 2M solution of pyridine in THF, carried out as a representative. The experimen­ 11 m2 (10 mmol) of 0.91 M lithium borohydride tal set-up and work-up procedure for analysis THF solution and 10 mZ (2.5 mm시) of 0.25 M of product were the same as in the previous THF solution of n-octane to serve as an inter­ experiments.