CN1810765A - Reduction of nitrile in nickel chloride/potassium borohydride reduction system to prepare amine - Google Patents
Reduction of nitrile in nickel chloride/potassium borohydride reduction system to prepare amine Download PDFInfo
- Publication number
- CN1810765A CN1810765A CN 200610020105 CN200610020105A CN1810765A CN 1810765 A CN1810765 A CN 1810765A CN 200610020105 CN200610020105 CN 200610020105 CN 200610020105 A CN200610020105 A CN 200610020105A CN 1810765 A CN1810765 A CN 1810765A
- Authority
- CN
- China
- Prior art keywords
- nitrile
- potassium borohydride
- add
- amine
- methyl alcohol
- 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.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention is reduction process of nitrile in a nickel chloride/potassium borohydride reduction system to prepare amine. By using potassium borohydride as reductant and nickel chloride as catalyst, nitrile may be reduced effectively into corresponding primary amine. By means of regulating the activity of the reduction system, 2-(1-hydroxy cyclohexyl)-2-(4-methoxy phenyl) acetonitrile may be reduced into 1-(2-amino-1-(4-methoxy phenyl) cyclohexanol as the intermediate for preparing phenylethyl amine antidepressant venlafaxine. By using potassium borohydride as reductant, the present invention has low cost, high safety, mild reaction condition at normal pressure, no need of N2 protection, primary amine yield over 80 %, less pollution and other advantages.
Description
Technical field
The present invention relates to the method that a kind of nitrile reducing prepares amine.
Background technology
As solvent, agricultural chemicals and medicine, nitrile reducing is a kind of method extremely important and commonly used for preparing amine to amine by widely.Yet nitrile is reduced into the stage that will experience imines in the process of amine, and this just forms coupled product (secondary amine) easily.So optionally nitrile reducing is that primary amine becomes a focus in recent years.Its method normally with lithium aluminum hydride or shortening (see (1) Walker.E.R.H.Chem.Soc.Rev.1976,5,23-50; (2) Klenke.B., Gilbert.I.H.J.Org.Chem.2001,66,2480-2483.) adopt the catalytic hydrogenation nitrile reducing, need High Temperature High Pressure usually.The main limitation of lithium aluminum hydride is to meet wet the decomposition and spontaneous combustion, easy initiation fire, and industrial production is dangerous big, and the price of lithium aluminum hydride, solvent load are big etc., and factor causes its use cost height.And the activity of sodium borohydride to be not enough to nitrile reducing be amine, need to add some auxiliary reagents usually and strengthen NaBH
4The active or primary amine of catching harsh one-tenth as human NiCl such as JitenderM.Khurana
2/ NaBH
4The aromatic nitrile of reduction system is that (see Khurana J.M., Kukreja G.Synthetic Communications 2002,32 (8) 1265-1269), but does not have effect preferably to aliphatic nitrile to primary amine.People such as Stephen Caddickt then use diacetyl oxide and (Boc)
2O catches the primary amine of formation, makes it (not see (1) StephenCaddick, Alexandra K.de K.Haynes, Duncan B.Judd and Meredith R.V.Williams Tetrahedron Letters 2000,41.3513-3516 with the imines coupling; (2) Stephen Caddick, Duncan B.Judd, Alexandra K.de K.Lewis; Melanie T.Reich and MeredithR.V.Williams Tetrahedron 2003; 59,5417-5423), also need to take off these blocking groups but will obtain primary amine.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of method for preparing primary amine with the nitrile reducing that nickelous chloride/POTASSIUM BOROHYDRIDE system selectivity is better, productive rate is higher, cost is lower is provided.
The structural formula of nitrile of the present invention is as follows:
R-CN
I II
Wherein: R is straight-chain alkyl, branched hydrocarbyl, substituted hydrocarbon radical etc.; R ' is alkyl, halogen, hydroxyl, amido, carboxyl etc.
Of the present invention is that the method for primary amine is as follows with nickelous chloride/POTASSIUM BOROHYDRIDE reduction system nitrile:
(1) in round-bottomed flask, adds 5-80mmol POTASSIUM BOROHYDRIDE, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol or methyl alcohol and 10mmol nitrile, stir--15～70 ℃ were stirred 30～120 minutes.
(2) boil off ethanol or methyl alcohol with Rotary Evaporators, add 5-100mL ethyl acetate or ether dissolution product, the separating funnel that changes over to washes with water 3 to 4 times, and organic phase changes round-bottomed flask over to, adds anhydrous siccative (Na
2SO
4Or MgSO
4) dried overnight.
(3) elimination siccative boils off ethyl acetate or ether with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain primary amine, productive rate 80%～92% with the aluminium sesquioxide column chromatography.
POTASSIUM BOROHYDRIDE (KBH
4) be a kind of metal hydride reducing agent, reducing power than sodium borohydride a little less than, price is more cheap than sodium borohydride, and stability is arranged preferably, spontaneous combustion, operational safety can not take place in air.The present invention has following beneficial effect with nickelous chloride/POTASSIUM BOROHYDRIDE reduction system nitrile:
(1) borane reducing agent potassium hydride KH economy, safety;
(2) the reaction conditions gentleness is carried out under normal pressure, does not need high-tension apparatus, does not need N
2In protection gas;
(3) reaction primary amine productive rate is high more than 80%, and speed is fast, and is easy and simple to handle, and solvent easily reclaims purifying, and cost is low, pollutes little.
Embodiment
Embodiment 1: present embodiment prepares phenylethylamine, and raw material is a benzyl cyanide:
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into-grain magnetic stirrer, add 0-80mL water, 5-80mL ethanol and 1.16mL (10mmol) benzyl cyanide ,-15～70 ℃ of stirrings.Boil off ethanol with Rotary Evaporators after 30 minutes, add 50mL acetic acid ethyl dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative, just Rotary Evaporators boils off ethyl acetate, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain the weak yellow liquid phenylethylamine, productive rate 90% with the aluminium sesquioxide column chromatography.
Embodiment 2: present embodiment prepares anisole ethamine, and raw material is a PARA METHOXY PHENYL ACETONITRILE
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol and 1.36mL (10mmol) PARA METHOXY PHENYL ACETONITRILE ,-15～70 ℃ of stirrings.After 30 minutes, filtrate boils off ethanol with Rotary Evaporators, adds 50mL acetic acid ethyl dissolution product, changes the separating funnel of 125mL over to, washes with water 3 to 4 times, and organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain colourless liquid to anisole ethamine, productive rate 89% with silica gel column chromatography.
Embodiment 3: present embodiment prepares chlorobenzene ethamine, and raw material is a p-chlorobenzyl cyanide
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol and 1.51g (10mmol) p-chlorobenzyl cyanide ,-15～70 ℃ of stirrings.Boil off ethanol with Rotary Evaporators after 30 minutes, add 50mL acetic acid ethyl dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain colourless liquid to anisole ethamine, productive rate 90% with the aluminium sesquioxide column chromatography.
Embodiment 4: present embodiment prepares n-amylamine, and raw material is positive valeronitrile
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add the positive valeronitrile of 25mL methyl alcohol and 1.05mL (10mmol) ,-15～70 ℃ of stirrings.Carefully boil off methyl alcohol with Rotary Evaporators after 30 minutes, add 50mL ether dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ether with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain the weak yellow liquid n-amylamine, productive rate 81% with the aluminium sesquioxide column chromatography.
Embodiment 5: the present embodiment preparation aligns amino dodecane, and raw material is positive lauronitrile
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, the positive lauronitrile of 5-80mL ethanol and 2.21mL (10mmol) ,-15～70 ℃ of stirrings.Boil off ethanol with Rotary Evaporators after 30 minutes, add 50mL acetic acid ethyl dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain the positive amino dodecane of white solid, productive rate 82% with the aluminium sesquioxide column chromatography.
Embodiment 6: present embodiment prepares benzene methanamine, and raw material is a cyanobenzene
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol and 1.02mL (10mmol) cyanobenzene ,-15-70 ℃ of stirring.Boil off ethanol with Rotary Evaporators after 45 minutes, add 50mL acetic acid ethyl dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain the weak yellow liquid benzene methanamine, productive rate 85% with titanium dioxide two aluminium column chromatographies.
Embodiment 7: present embodiment prepares m-methyl-phenyl-methyl amine, raw material be between basic cyanobenzene
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, methyl benzonitrile between 5-80mL ethanol and 1.21mL (10mmol) ,-15～70 ℃ of stirrings.Boil off ethanol with Rotary Evaporators after 45 minutes, add 50mL acetic acid ethyl dissolution product, change the separatory bucket of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain the weak yellow liquid m-methyl-phenyl-methyl amine, productive rate 81% with the aluminium sesquioxide column chromatography.
Embodiment 8: present embodiment prepares the O-ethoxyl methylamine, and raw material is the O-ethoxyl formonitrile HCN
In round-bottomed flask, add 5-80mmol KBH
4, 1-80mmolNiCl
2, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol and 1.47g (10mmol) O-ethoxyl formonitrile HCN ,-15～70 ℃ of stirrings.Boil off ethanol with Rotary Evaporators after 45 minutes, add 50mL acetic acid ethyl dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain white solid O-ethoxyl methylamine, productive rate 80% with the aluminium sesquioxide column chromatography.
Embodiment 9: present embodiment prepares 1-(2-amino-1-(4-p-methoxy-phenyl) ethyl) hexalin, and raw material is 2-(1-hydroxy-cyclohexyl)-2-(4-p-methoxy-phenyl) acetonitrile
In round-bottomed flask, add 5-80mmol KBH
4, add 1.27g (10mmol) nickelous chloride, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol and 2.45g (10mmol) 2-(1-hydroxy-cyclohexyl)-2-(4-p-methoxy-phenyl) acetonitrile ,-15～70 ℃ of stirrings.Boil off ethanol with Rotary Evaporators after 2 hours, add 50mL acetic acid ethyl dissolution product, change the separating funnel of 125mL over to, wash with water 3 to 4 times, organic phase changes the 100mL round-bottomed flask over to, adds anhydrous Na
2SO
4Dried overnight, the elimination siccative boils off ethyl acetate with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain white solid 1-(2-amino-1 (4-methoxyphenyl) ethyl) hexalin, productive rate 87% with the aluminium sesquioxide column chromatography.
Claims (1)
1. nickelous chloride/potassium borohydride reduction reduction system nitrile prepares the amine method, and the structural formula of described nitrile is as follows:
R-CN
I II
Wherein: R is straight-chain alkyl, branched hydrocarbyl, substituted hydrocarbon radical etc.; R ' is alkyl, halogen, hydroxyl, amido, carboxyl etc.It is characterized in that POTASSIUM BOROHYDRIDE is a reductive agent, nickelous chloride is a catalyzer, and nitrile reducing is that the method for primary amine is as follows:
(1) in dry round-bottomed flask, adds 5-80mmol POTASSIUM BOROHYDRIDE, 1-80mmol NiCl
2, put into a magnetic stirrer, add 0-80mL water, 5-80mL ethanol or methyl alcohol and 10mmol nitrile, stir--15～70 ℃ were stirred 30～120 minutes.
(2) boil off ethanol or methyl alcohol with Rotary Evaporators, add 5-100mL ethyl acetate or ether dissolution product, the separating funnel that changes over to washes with water 3 to 4 times, and organic phase changes round-bottomed flask over to, adds anhydrous siccative (Na
2SO
4Or MgSO
4) dried overnight.
(3) elimination siccative boils off ethyl acetate or ether with Rotary Evaporators, and (developping agent is a methylene dichloride: methyl alcohol 20: 1), obtain primary amine, productive rate 80%～92% with the aluminium sesquioxide column chromatography.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610020105 CN1810765A (en) | 2006-01-04 | 2006-01-04 | Reduction of nitrile in nickel chloride/potassium borohydride reduction system to prepare amine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610020105 CN1810765A (en) | 2006-01-04 | 2006-01-04 | Reduction of nitrile in nickel chloride/potassium borohydride reduction system to prepare amine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1810765A true CN1810765A (en) | 2006-08-02 |
Family
ID=36843906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610020105 Pending CN1810765A (en) | 2006-01-04 | 2006-01-04 | Reduction of nitrile in nickel chloride/potassium borohydride reduction system to prepare amine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1810765A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008083708A1 (en) * | 2007-01-09 | 2008-07-17 | Pharmathen S.A. | Improved process for the preparation of phenethylamine derivatives |
| CN103965057A (en) * | 2014-04-25 | 2014-08-06 | 浙江普洛医药科技有限公司 | Method for preparing primary amine from nitrile |
| CN107216256A (en) * | 2017-05-19 | 2017-09-29 | 江苏斯威森生物医药工程研究中心有限公司 | A kind of synthetic method of N, N diisopropyl ethylenediamine |
| CN110066221A (en) * | 2019-05-16 | 2019-07-30 | 海门瑞一医药科技有限公司 | A kind of preparation method of cyclopropyl-methylamine |
-
2006
- 2006-01-04 CN CN 200610020105 patent/CN1810765A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008083708A1 (en) * | 2007-01-09 | 2008-07-17 | Pharmathen S.A. | Improved process for the preparation of phenethylamine derivatives |
| CN103965057A (en) * | 2014-04-25 | 2014-08-06 | 浙江普洛医药科技有限公司 | Method for preparing primary amine from nitrile |
| CN103965057B (en) * | 2014-04-25 | 2015-12-30 | 浙江普洛医药科技有限公司 | A kind of nitrile prepares the method for primary amine |
| CN107216256A (en) * | 2017-05-19 | 2017-09-29 | 江苏斯威森生物医药工程研究中心有限公司 | A kind of synthetic method of N, N diisopropyl ethylenediamine |
| CN110066221A (en) * | 2019-05-16 | 2019-07-30 | 海门瑞一医药科技有限公司 | A kind of preparation method of cyclopropyl-methylamine |
| CN110066221B (en) * | 2019-05-16 | 2022-03-08 | 海门瑞一医药科技有限公司 | Preparation method of cyclopropylmethylamine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1810766A (en) | Nitrile reducing process to prepare amine | |
| Hayashi et al. | Asymmetric Diels–Alder reactions of α, β‐unsaturated aldehydes catalyzed by a diarylprolinol silyl ether salt in the presence of water | |
| DE112014002844B4 (en) | NHC palladium catalyst and its production process and use | |
| CN100522926C (en) | Preparation method of memantine salt | |
| CN113372241B (en) | Method for synthesizing dinitrile ethyl tertiary amine by aliphatic primary amine one-step method | |
| CN1810765A (en) | Reduction of nitrile in nickel chloride/potassium borohydride reduction system to prepare amine | |
| CN101602015B (en) | Cyclohexane ionic liquid catalyst prepared from benzene and hydrogen and preparation method thereof | |
| CN104557564B (en) | Preparation method of phenylmethylamine | |
| US20040106818A1 (en) | Process for the preparation of cyclohexanol derivatives | |
| DE60307686T2 (en) | Hydrogenation of single-ring aromatic diamines | |
| CN107118125B (en) | A kind of preparation method of cyclohexanone oxime | |
| CN108273507B (en) | Method for reducing nitrile compound by catalytic hydrogenation | |
| CN103497157B (en) | 2-imidazolidone synthesis method | |
| Maj et al. | Asymmetric hydrogenation of 2, 3-dihydro-1H-inden-1-one oxime and derivatives | |
| CN1966476A (en) | Iron-catalysed allylic alkylation | |
| CN102199098B (en) | New synthesis method and application of (R)-N-benzyl-1-(4-methoxyphenyl)-2-propylamine | |
| CN103965057B (en) | A kind of nitrile prepares the method for primary amine | |
| JP2001354598A (en) | Method of producing adamantane | |
| CN103193660B (en) | Synthetic method of 4-alkoxy phenylamine compound | |
| US11299451B2 (en) | Method for synthesizing 2-(1-cyclohexenyl)ethylamine | |
| CN102660012B (en) | Preparation method of hydroxy-terminated perfluoropolyether compound | |
| CN116143658A (en) | Method for simultaneously preparing tripropylacetonitrile, tripropylamide and tripropylacetic acid | |
| CN109748817B (en) | Method for synthesizing aliphatic nitrile from aliphatic aldehyde | |
| WO1998033766A1 (en) | Process for the preparation of cyanoarylmethylamine | |
| CN101318144A (en) | Catalyst for preparing amide compounds, synthesis and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Yu Xiaoqi Document name: Deemed as a notice of withdrawal (Trial) |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |