JPH0566951B2 - - Google Patents
Info
- Publication number
- JPH0566951B2 JPH0566951B2 JP60127130A JP12713085A JPH0566951B2 JP H0566951 B2 JPH0566951 B2 JP H0566951B2 JP 60127130 A JP60127130 A JP 60127130A JP 12713085 A JP12713085 A JP 12713085A JP H0566951 B2 JPH0566951 B2 JP H0566951B2
- Authority
- JP
- Japan
- Prior art keywords
- catalyst
- hexahydronicotine
- solvent
- amount
- rbhh
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- BPOJUAZWENUSBT-UHFFFAOYSA-N 3-(1-methylpyrrolidin-2-yl)piperidine Chemical compound CN1CCCC1C1CNCCC1 BPOJUAZWENUSBT-UHFFFAOYSA-N 0.000 claims description 7
- 229910052759 nickel Inorganic materials 0.000 claims description 6
- 229910052763 palladium Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229960002715 nicotine Drugs 0.000 description 3
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- HDJBTCAJIMNXEW-PPHPATTJSA-N 3-[(2s)-1-methylpyrrolidin-2-yl]pyridine;hydrochloride Chemical compound Cl.CN1CCC[C@H]1C1=CC=CN=C1 HDJBTCAJIMNXEW-PPHPATTJSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical class [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
（産業上の利用分野）
本発明はヘキサハイドロニコチンの製造方法に
関する。
たばこの健康医学的研究分野において、ニコチ
ンの研究は従来より詳細になされて来ている。そ
の中で、ニコチンの立体的、構造的特徴を研究す
る上で、ヘキサハイドロニコチンを含む各種ニコ
チン誘導体の研究がなされて来た。また、ヘキサ
ハイドロニコチンは、bactericideやfungicideの
合成中間体としても重要な物質である。
（従来の技術）
ヘキサハイドロニコチンは、従来、ニコチンを
エタノール中、ナトリウムで還元して得る方法
（Ber.，18，2969（1885））、及びニコチンの塩酸塩
をラネーニツケル又は白金などを触媒として、高
温高圧下接触水素化して得られている（US特許
2834784（1958）J.A.C.S，52，3385（1930））。
（発明が解決しようとする問題点）
しかし、従来の製造方法は極めてきびしい反応
条件が要求され、又そのために反応生成物は、
2′位も還元されたオクタハイドロニコチンを含む
各種の混合物として得られ、それらの分離が困難
であるという欠点を有する。
本発明は、このような従来の公知の製造方法に
伴なう欠点がなく、反応条件も温和で選択性も高
く、又、2′S，3R−及び2′S，3S−ヘキサハイド
ロニコチンの２種類のジアステレオマーの分離も
容易な製造方法を提供することを目的としたもの
である。
（問題を解決するための手段）
すなわち、本発明は、公知の方法で得られる１
−ベンジルニコチニウム塩を、ナトリウムボロハ
イドライド（以下「NaBH4」と表わす）で還元
し、１−ベンジル−１，２，５，６−テトラハイ
ドロニコチン（以下「BZTH」と表わす）を得、
次いで、ニツケルで水素添加し、2′S，3R−１−
ベンジルヘキサハイドロニコチン（以下
「RBHH」と表わす）及び、2′S，3S−１−ベン
ジルヘキサハイドロニコチン（以下「SBHH」
と表わす）を混合物として得る。このようにして
得られた混合物を、メタノール；水混合液を展開
溶媒として、逆相クロマトグラフで分離した後、
それぞれを、触媒の存在下、加水素分解し、式１
に示す2′S，3R−ヘキサハイドロニコチン（以下
「化合物１」と表わす）及び、式２に示す2′S，
3S−ヘキサハイドロニコチン（以下「化合物２」
と表わす）をそれぞれ得る製造方法である。以下
に、その製造方法を後述の製造例にもとづき詳細
に説明する。
(Industrial Application Field) The present invention relates to a method for producing hexahydronicotine. In the field of tobacco health and medical research, nicotine has been studied in more detail than ever before. Among these, various nicotine derivatives including hexahydronicotine have been studied in order to study the steric and structural characteristics of nicotine. Hexahydronicotine is also an important substance as a synthetic intermediate for bacterialicide and fungicide. (Prior Art) Hexahydronicotine has conventionally been obtained by reducing nicotine with sodium in ethanol (Ber., 18, 2969 (1885)), and by reducing nicotine hydrochloride using Raney nickel or platinum as a catalyst. Obtained by catalytic hydrogenation under high temperature and high pressure (US patent)
2834784 (1958) JACS, 52, 3385 (1930)). (Problems to be Solved by the Invention) However, the conventional production method requires extremely severe reaction conditions, and as a result, the reaction product is
The drawback is that various mixtures containing octahydronicotine, which is also reduced at the 2' position, are obtained, and their separation is difficult. The present invention does not have the drawbacks associated with conventionally known production methods, has mild reaction conditions and high selectivity, and can produce 2'S,3R- and 2'S,3S-hexahydronicotine. The purpose of this invention is to provide a manufacturing method that allows easy separation of two types of diastereomers. (Means for solving the problem) That is, the present invention provides 1 obtained by a known method.
- reducing benzylnicotinium salt with sodium borohydride (hereinafter referred to as " NaBH4 ") to obtain 1-benzyl-1,2,5,6-tetrahydronicotine (hereinafter referred to as "BZTH"),
Next, hydrogenation was performed with nickel to give 2'S,3R-1-
Benzylhexahydronicotine (hereinafter referred to as "RBHH") and 2'S,3S-1-benzylhexahydronicotine (hereinafter referred to as "SBHH")
) is obtained as a mixture. The mixture thus obtained was separated by reverse phase chromatography using a methanol/water mixture as a developing solvent.
Each was hydrolyzed in the presence of a catalyst to form the formula 1
2'S,3R-hexahydronicotine (hereinafter referred to as "compound 1") shown in Formula 2, and 2'S,3R-hexahydronicotine shown in Formula 2,
3S-hexahydronicotine (hereinafter referred to as “Compound 2”)
). The manufacturing method will be described in detail below based on manufacturing examples described later.
【式】
公知の方法で得られる１−ベンジルニコチニウ
ム塩、望ましくは１−ベンジルニコチニウムブロ
ミドを、それに対し10〜20倍量、望ましくは12倍
量の水又はメタノール又はエタノール等のプロト
ン性溶媒、望ましくは水に溶解させ、水冷下、１
−ベンジルニコチニウムブロミドに対し、３〜10
倍量、望ましくは５倍量のNaBH4を約１時間か
けてゆつくり加える。反応後、少量の塩酸を加え
て溶液を酸性にし、次いで水酸化ナトリウムなど
のアルカリ性水溶液を加えてアルカリ性にした
後、エーテル又はクロロフオルムなどの有機溶媒
で抽出し、硫酸ナトリウムなどで乾燥させた後、
減圧下で溶媒を留去させ、次いで、153℃、２mm
Hgの条件下で減圧蒸留にかけBZTHを収率70〜
80％で得た。
得られたBZTHを、BZTHに対し10〜30倍量、
望ましくは15倍量のメタノールに溶解させ、ニツ
ケル、望ましくは活性ラネーニツケル触媒を、
BZTHに対し、0.01〜0.5倍量、望ましくは0.2倍
量加え、室温、常圧、水素ガス雰囲気下で５〜24
時間、望ましくは10時間反応させる。反応後、ニ
ツケルをろ別し、減圧下溶媒を留去させると、
RBHH，SBHHを、混合物として収率90〜95％
で得る。
得られたRBHH及びSBHHの混合物を、メタ
ノール；水混合液（溶量比１：１〜５：１、望ま
しくは３：１）を展開溶媒とした逆相クロマトグ
ラフにかけ、RBHH，SBHHをBZTHに対しそ
れぞれ65〜75％、15〜30％の収率で得た。
次いで、得られたRBHH，SBHHをそれぞれ
エーテルに溶解させ、乾燥塩化水素ガスを通した
後、それぞれの塩酸塩をろ取し、次いで、それぞ
れの塩酸塩に対し、10〜20倍量、望ましくは15倍
量のメタノールに溶解させ、それぞれの塩酸塩に
対し0.01〜0.1倍量の触媒、望ましくはパラジウ
ムー活性炭を加え、室温、常圧、水素ガス雰囲気
下で２〜10時間、望ましくは４時間反応させる。
反応後、触媒をろ別し、減圧下溶媒を留去する。
ここで使用する触媒はパラジウムに限定されるも
のではなく、他のものでもよい。得られた油状物
質を適当量の水に溶解させ水酸化ナトリウム等の
アルカリ水溶液を加えてアルカリ性にした後、エ
ーテル又はクロロフオルム等の有機溶媒で抽出
し、硫酸ナトリウム等で乾燥させた後、減圧下溶
媒を留去させる。次いで、石油エーテルで低温下
再結晶させることにより、化合物１及び、化合物
２をそれぞれ90〜98％、85〜95％の収率で得るこ
とができる。
（製造例）
500mlビーカー中、6.7ｇ（20mmol）の１−ベ
ンジルニコチニウムブロミドを、水80mlに溶解さ
せた水冷下、攪拌させながらその溶液中に
NaBH43.8ｇ（100mmol）を１時間かけてゆつく
り加える。反応後、適当量の塩酸を加え溶液を酸
性（PH＜３）にした後、水酸化ナトリウム水溶液
を加えてアルカリ性（PH＞11）にし、エーテルで
抽出し、硫酸ナトリウムで乾燥させ溶媒を減圧下
留去させる。次いで、153℃、２mmHgの条件下で
減圧蒸留にかけると、BZTHが4.1ｇ（収率80％）
得られた。
得られたBZTH4.1ｇ（16mmol）を、100mlシ
ユレンク中60mlのメタノールに溶解させる。公知
の方法で活性化されたラネーニツケル（Ｒ−４）
0.8ｇをその溶液中に加え、攪拌させながら、水
素ガスを注入する。気相を水素雰囲気下にするた
め、３回ガス置換を行なつた後、室温、常圧下10
時間撹拌させる。反応後、ラネーニツケルをろ別
し、減圧下溶媒を留去させるとRBHHとSBHH
が混合物として3.9ｇ（収率95％）得られる。
メタノール、水（溶量比３：１）混合液を展開
溶媒としたC18逆相クロマトグラフ（ODS，22mm
φ×50cm）にかけてRBHHとSBHHを分離し、
それぞれ2.8ｇ（収率72％）、0.9ｇ（収率23％）
得られた。
次いで、得られたRBHH2.8ｇ（11mmol）を
10mlのエーテルに溶解させた後、乾燥塩化水素ガ
スを注入する。得られたRBHHの塩酸塩をろ取
し、10mlのメタノールに溶解させる。100mlシユ
レンクに0.2ｇの５％パラジウムー活性炭を入れ、
メタノール35mlを加えた後、撹拌しながら水素ガ
スを注入する。気相を水素雰囲気下にするため、
３回ガス置換を行なつた後、水素雰囲気下で５分
間撹拌させる。次いで、RBHHの塩酸塩を含む
メタノール溶液を加え、室温、常圧下で４時間撹
拌させる。反応後、パラジウムー活性炭をろ別
し、減圧下溶媒を留去させる。得られた油状物質
を10mlの水に溶解させ、水酸化ナトリウム水溶液
を加えアルカリ性（PH＞11）にした後、エーテル
で抽出し、硫酸ナトリウムで乾燥させ、減圧下溶
媒を留去させる。低温下（０℃）、石油エーテル
で再結晶させると、化合物１が1.8ｇ（収率95％）
得られる。
SBHH0.9ｇ（3.5mmol）を上に述べた方法で
加水素分解すると、化合物２が0.5ｇ（収率90％）
得られる。
（発明の効果）
以上詳細に説明したように、本発明による製造
方法は、反応条件がいずれの行程においても温和
であり、又、反応の選択性が極めて高く、かつ、
２種類のジアステレオマーの分離が容易であると
いう利点を有している。[Formula] 1-benzylnicotinium salt obtained by a known method, preferably 1-benzylnicotinium bromide, in an amount of 10 to 20 times, preferably 12 times the amount of water or a protic solvent such as methanol or ethanol. , preferably dissolved in water and cooled with water, 1
- 3 to 10 for benzylnicotinium bromide
Double the amount, preferably 5 times the amount of NaBH 4 is slowly added over about an hour. After the reaction, the solution is made acidic by adding a small amount of hydrochloric acid, then made alkaline by adding an alkaline aqueous solution such as sodium hydroxide, extracted with an organic solvent such as ether or chloroform, and dried with sodium sulfate, etc.
The solvent was distilled off under reduced pressure, and then heated at 153°C for 2 mm.
The yield of BZTH is 70~ by vacuum distillation under Hg conditions.
Got it at 80%. The obtained BZTH is 10 to 30 times the amount of BZTH,
Nickel, preferably activated Raney nickel catalyst, is dissolved in preferably 15 times the amount of methanol.
Add 0.01 to 0.5 times the amount, preferably 0.2 times the amount of BZTH, and leave for 5 to 24 hours at room temperature, normal pressure, and hydrogen gas atmosphere.
The reaction time is preferably 10 hours. After the reaction, the nickel is filtered off and the solvent is distilled off under reduced pressure.
RBHH, SBHH as a mixture yield 90-95%
Get it. The resulting mixture of RBHH and SBHH was subjected to reverse phase chromatography using a methanol/water mixture (volume ratio 1:1 to 5:1, preferably 3:1) as a developing solvent, and RBHH and SBHH were converted to BZTH. The yields were 65-75% and 15-30%, respectively. Next, the obtained RBHH and SBHH are each dissolved in ether, and after dry hydrogen chloride gas is passed through, each hydrochloride is collected by filtration, and then 10 to 20 times the amount of each hydrochloride, preferably Dissolve in 15 times the volume of methanol, add 0.01 to 0.1 times the amount of catalyst, preferably palladium-activated carbon, to each hydrochloride, and react at room temperature, normal pressure, and hydrogen gas atmosphere for 2 to 10 hours, preferably 4 hours. let
After the reaction, the catalyst is filtered off and the solvent is distilled off under reduced pressure.
The catalyst used here is not limited to palladium, but other catalysts may also be used. The obtained oily substance is dissolved in an appropriate amount of water, made alkaline by adding an alkaline aqueous solution such as sodium hydroxide, extracted with an organic solvent such as ether or chloroform, dried with sodium sulfate, etc., and then dissolved under reduced pressure. The solvent is distilled off. Then, by recrystallizing with petroleum ether at low temperature, Compound 1 and Compound 2 can be obtained in yields of 90 to 98% and 85 to 95%, respectively. (Production example) In a 500 ml beaker, 6.7 g (20 mmol) of 1-benzylnicotinium bromide was dissolved in 80 ml of water.
Slowly add 3.8g (100mmol) of NaBH 4 over 1 hour. After the reaction, add an appropriate amount of hydrochloric acid to make the solution acidic (PH < 3), add an aqueous sodium hydroxide solution to make it alkaline (PH > 11), extract with ether, dry over sodium sulfate, and remove the solvent under reduced pressure. Distillate. Then, by vacuum distillation at 153℃ and 2mmHg, 4.1g of BZTH (80% yield) was obtained.
Obtained. 4.1 g (16 mmol) of the BZTH obtained is dissolved in 60 ml of methanol in 100 ml of Schulenk. Raneynickel (R-4) activated by known methods
Add 0.8 g to the solution and inject hydrogen gas while stirring. After replacing the gas three times to bring the gas phase into a hydrogen atmosphere, it was heated at room temperature and normal pressure for 10 minutes.
Stir for an hour. After the reaction, Raney nickel is filtered off and the solvent is distilled off under reduced pressure to form RBHH and SBHH.
3.9 g (yield 95%) is obtained as a mixture. C18 reverse phase chromatograph (ODS, 22 mm) using methanol and water (3:1 ratio) as the developing solvent.
φ×50cm) to separate RBHH and SBHH,
2.8g (yield 72%) and 0.9g (yield 23%) respectively
Obtained. Next, 2.8 g (11 mmol) of the obtained RBHH was added to
After dissolving in 10 ml of ether, dry hydrogen chloride gas is injected. The obtained RBHH hydrochloride is collected by filtration and dissolved in 10 ml of methanol. Add 0.2g of 5% palladium-activated carbon to 100ml Schulenk,
After adding 35 ml of methanol, hydrogen gas is injected while stirring. In order to put the gas phase under a hydrogen atmosphere,
After performing gas replacement three times, the mixture was stirred for 5 minutes under a hydrogen atmosphere. Next, a methanol solution containing the hydrochloride of RBHH is added, and the mixture is stirred at room temperature and normal pressure for 4 hours. After the reaction, the palladium-activated carbon is filtered off, and the solvent is distilled off under reduced pressure. The resulting oily substance is dissolved in 10 ml of water, made alkaline (PH > 11) by adding an aqueous sodium hydroxide solution, extracted with ether, dried over sodium sulfate, and the solvent is distilled off under reduced pressure. When recrystallized from petroleum ether at low temperature (0℃), 1.8g of compound 1 (yield 95%)
can get. When 0.9 g (3.5 mmol) of SBHH is hydrolyzed by the method described above, 0.5 g of compound 2 (90% yield) is obtained.
can get. (Effects of the Invention) As explained in detail above, in the production method of the present invention, the reaction conditions are mild in all steps, the selectivity of the reaction is extremely high, and
It has the advantage that two types of diastereomers can be easily separated.
Claims (1)
ロハイドライドで還元した後ニツケルを触媒とし
て水素添加して得られる化合物を触媒の存在下、
加水素分解することを特徴とするヘキサハイドロ
ニコチンの製造方法。 ２ １−ベンジルニコチニウム塩をナトリウムボ
ロハイドライドで還元し、ニツケルを触媒として
水素添加した後、分離精製して得られる2′S，3R
−１−ベンジルヘキサハイドロニコチンをパラジ
ウムを触媒として加水素分解することを特徴とす
る特許請求の範囲第１項記載のヘキサハイドロニ
コチンの製造方法。 ３ １−ベンジルニコチニウム塩をナトリウムボ
ロハイドライドで還元し、ニツケルを触媒として
水素添加した後、分離精製して得られる2′S，3S
−１−ベンジルヘキサハイドロニコチンをパラジ
ウムを触媒として加水素分解することを特徴とす
る特許請求の範囲第１項記載のヘキサハイドロニ
コチンの製造方法。[Claims] 1 A compound obtained by reducing 1-benzylnicotinium salt with sodium borohydride and then hydrogenating it using nickel as a catalyst, in the presence of a catalyst,
A method for producing hexahydronicotine, which is characterized by hydrolysis. 2 2′S, 3R obtained by reducing 1-benzylnicotinium salt with sodium borohydride, hydrogenating it using nickel as a catalyst, and then separating and purifying it.
The method for producing hexahydronicotine according to claim 1, characterized in that -1-benzylhexahydronicotine is hydrolyzed using palladium as a catalyst. 3 2′S, 3S obtained by reducing 1-benzylnicotinium salt with sodium borohydride, hydrogenating it using nickel as a catalyst, and then separating and purifying it.
The method for producing hexahydronicotine according to claim 1, characterized in that -1-benzylhexahydronicotine is hydrolyzed using palladium as a catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60127130A JPS61286377A (en) | 1985-06-13 | 1985-06-13 | Production of hexahydronicotine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60127130A JPS61286377A (en) | 1985-06-13 | 1985-06-13 | Production of hexahydronicotine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61286377A JPS61286377A (en) | 1986-12-16 |
| JPH0566951B2 true JPH0566951B2 (en) | 1993-09-22 |
Family
ID=14952352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60127130A Granted JPS61286377A (en) | 1985-06-13 | 1985-06-13 | Production of hexahydronicotine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61286377A (en) |
-
1985
- 1985-06-13 JP JP60127130A patent/JPS61286377A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61286377A (en) | 1986-12-16 |
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