CN106905166B - A method of synthesis secondary amine - Google Patents
A method of synthesis secondary amine Download PDFInfo
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- CN106905166B CN106905166B CN201710095254.XA CN201710095254A CN106905166B CN 106905166 B CN106905166 B CN 106905166B CN 201710095254 A CN201710095254 A CN 201710095254A CN 106905166 B CN106905166 B CN 106905166B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/14—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups
- C07C209/18—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
A method of synthesis secondary amine includes the following steps：Under the protection of nitrogen or argon gas; by 0.05 0.4mol cobalt complexes and 0.8 1.5mol additives in nonpolar solvent of the room-temperature dissolution in 5mg; magneton stirs; thereafter 8 12mol primary alconols and 11 13mol primary amine derivatives are separately added into, 120oC will be heated in oil bath after the glass seal of tube, be stirred overnight; 24 hours postcoolings are reacted to room temperature; solvent under reduced pressure is distilled, crude product passes through silica gel post separation, as secondary amine derivative.
Description
Technical field
The present invention relates to chemical fields, and in particular to a method of synthesis secondary amine.
Background technology
Currently, aminated compounds is most universal, most important organic synthesis raw material and intermediate, the synthesis of amine is also to learn
One of art circle and the most important research topic of industry.The N- alkylations of primary amine are the common sides of chemical synthesis and intermediate synthesis
Method, synthetic route and method are also relatively more, and synthetic product is not only in the compound and pharmaceutical synthesis of rubber, oil etc. most
Common intermediate.Such as general antiozonant, gasoline additive of N, the N'- di-sec-butyl-p-phenyl enediamine as rubber；N,
N- diethyl arylamine is the important intermediate for preparing dyestuff, drug and color developer；N, N- dimethyl arylamine are important dye
Expect intermediate, can be used for manufacturing alkaline bright yellow, Basic Violet 5BN, alkalescent light green, Methylene Blue BB, gorgeous indigo plant etc., it may also be used for doctor
Medicine manufacture, the production of fragrance vanillic aldehyde, thiofide etc.；P-isopropyl arylamine is the main original of synthetic herbicide isoproturon
Material, and synthesize the important intermediate of other pesticides and drug products.
Traditionally, secondary amine is mainly anti-by the nucleophilic substitution and aldehyde ketone of primary amine and halogenated hydrocarbons and the reduction amination of amine
It should prepare.And how to ensure the selectivity of this kind of reaction, and it is the research of secondary amine synthesis to avoid the high toxicity of alkylating reagent
Trend.' to borrow hydrogen（Or hydrogen shifts certainly）' reaction be representative novel amine synthetic reaction have very high Atom economy, because
This becomes one of the important research direction of current Green Chemistry.
Refer to the organic molecule with metallic catalyst by relative inertness by means of hydrogen amine synthetic reaction（Such as primary alconol or amine）Catalysis is de-
Hydrogen, and the metal hydride catalyst intermediate of high activity is formed, dehydrogenation product forms intermediate with amine coupling thereafter, then gold
Belong to the reaction that hydride catalytic agent recycles the hydrogen molecule that front discharges by intermediate reduction at secondary amine.For example, amine and alcohol are borrowed
Hydrogen reaction generates secondary amine and a molecular water, and primary amine, which is reacted with amine by means of hydrogen, generates secondary amine and a molecule ammonia.This method was both succinct
Efficiently, and it is environmentally protective.It is reported in succession in recent years as the noble metal catalyst of representative using ruthenium and iridium.Although these catalyst have
There is extensive substrate applicability, but because these metal prices are high and toxic, the cheap and less toxic metallic catalyst of development
（Such as manganese, iron, cobalt etc.）It is one of the significant challenge of current Green Chemistry.
In recent years, Ji Zhongtie, cobalt have been applied to primary amine as non-precious metal catalyst and react and synthesize by means of hydrogen with alcohol
Secondary amine.But these catalyst all utilize phosphorus-containing ligand, and the price of its low stability and costliness significantly limits them
Application industrially.
Invention content
The purpose of the present invention provides a kind of method of synthesis secondary amine aiming at deficiency above-mentioned at present.
A method of synthesis secondary amine includes the following steps：
Under the protection of nitrogen or argon gas, by 0.05-0.4mol cobalt complexes and 0.8-1.5mol additives in room-temperature dissolution
In the nonpolar solvent of 5mg, magneton stirring is separately added into thereafter 8-12mol primary alconols and 11-13mol primary amine derivatives, by glass
120 oC are heated to after the glass seal of tube in oil bath, are stirred overnight, 24 hours postcoolings of reaction steam solvent under reduced pressure to room temperature
It evaporates, crude product passes through silica gel post separation, as secondary amine derivative.
Primary alconol is benzyl alcohol, 4- methoxy benzyl alcohols or n-hexyl alcohol.
Primary amine derivatives are aniline or 4- aminoanisoles.
Following synthetic methods for cobalt complex：
Under room temperature, in 25 milliliters of round-bottomed flasks, by 10mol 2,2 ';6 ', 2 ' '-terpyridyl is dissolved in 10mL
In THF, 10mol cobalt chlorides are then added, after acquired solution is stirred overnight, filtering, after gained light green solid is washed with THF,
Dry sterling is cobalt complex.
The solvent can be toluene, ethylbenzene, tetrahydrofuran.
Additive can be potassium tert-butoxide or sodium tert-butoxide.
The alcohol is the primary alconol amine containing R1.
The method have the advantages that：It is a kind of to borrow hydrogen by catalytic amine -ol using simple, cheap and air-stable Co catalysts
Synthesize the reaction of secondary amine.Compared to known catalysis process, which has the following advantages：1）Catalyst preparation is simple, efficient；
2）Catalyst is without precious metal, cheap, and has very high chemical stability；3）Catalytic process is selectively good, without other
Side reaction, and it is efficient, environmentally protective.Using simple cobalt complex as catalyst, selectivity synthesis secondary amine derivative,
Easy to operate, at low cost, high income can carry out high-volume synthesis, be suitble to industrial production application.The reaction efficiency is high, chemistry selects
Selecting property is excellent, by-product is pollution-free and iodine effect stability, suitable for high-volume commercial Application.Reaction substrate is simple and easy to get,
It can be used as the excellent approach of synthesis secondary amine and derived product.R1 and R2 substituent group ranges in its structural unit are wide, can fit
For aliphatic chain, cycloalkane, aromatic hydrocarbon.Therefore it is widely used, can be used for preparing the raw material of a variety of pharmaceutical intermediates.
Specific implementation mode
Under the protection of nitrogen or argon gas, by 0.05-0.4mol cobalt complexes and 0.8-1.5mol additives in room-temperature dissolution
In the nonpolar solvent of 5mg, magneton stirring is separately added into thereafter 8-12mol primary alconols and 11-13mol primary amine derivatives, by glass
120 oC are heated to after the glass seal of tube in oil bath, are stirred overnight, 24 hours postcoolings of reaction steam solvent under reduced pressure to room temperature
It evaporates, crude product passes through silica gel post separation, as secondary amine derivative.
The present invention is further explained in the light of specific embodiments.
The general formula of reaction in the embodiment of the present invention is as follows：
Wherein R1 represent carbon atom number as 2~8 alkyl group, carbon atom number is 5~8 naphthenic base, phenyl, substituted benzene
Base.R2 represents substituted-phenyl, carbon atom number as 2~8 alkyl group.
Embodiment one：
N2Under protection, in 100 milliliters of horminess glass tubes be added Co catalysts (0.02 mmol, 2 mol%) and
Potassium tert-butoxide（11.2 mg, 0.10 mmol, 10 mol%）, 5 milliliters of toluene, magneton stirring is then added.Thereafter it is separately added into
Benzyl alcohol (108.0 mg, 1.0mmol) and aniline (111.6 mg, 1.2mmol).It will be heated in oil bath after the glass seal of tube
To 120 oC, it is stirred overnight.24 hours postcoolings are reacted to room temperature, solvent under reduced pressure are distilled, crude product passes through silica gel post separation
（Eluant, eluent：Ethyl acetate/hexane：1：5）.Yield：168 milligrams（92%）.
Embodiment two：
N2Under protection, in 100 milliliters of horminess glass tubes be added Co catalysts (0.02 mmol, 2 mol%) and
Potassium tert-butoxide（11.2 mg, 0.10 mmol, 10 mol%）, 5 milliliters of toluene, magneton stirring is then added.Thereafter it is separately added into
Benzyl alcohol (108.0 mg, 1.0mmol) and 4- aminoanisoles (147.6 mg, 1.2mmol).By after the glass seal of tube in oil
It is heated to 120 oC in bath, is stirred overnight.24 hours postcoolings are reacted to room temperature, solvent under reduced pressure are distilled, crude product passes through silicon
Rubber column gel column detaches（Eluant, eluent：Ethyl acetate/hexane：1：5）.Yield：192 milligrams（90%）.
Embodiment three：
N2Under protection, in 100 milliliters of horminess glass tubes be added Co catalysts (0.02 mmol, 2 mol%) and
Potassium tert-butoxide（11.2 mg, 0.10 mmol, 10 mol%）, 5 milliliters of toluene, magneton stirring is then added.Thereafter it is separately added into
4- methoxy benzyl alcohols (138.0 mg, 1.0mmol) and aniline (111.6 mg, 1.2mmol).By after the glass seal of tube in oil
It is heated to 120 oC in bath, is stirred overnight.24 hours postcoolings are reacted to room temperature, solvent under reduced pressure are distilled, crude product passes through silicon
Rubber column gel column detaches（Eluant, eluent：Ethyl acetate/hexane：1：5）.Yield：181 milligrams（85%）.
Example IV：
N2Under protection, in 100 milliliters of horminess glass tubes be added Co catalysts (0.02 mmol, 2 mol%) and
Potassium tert-butoxide（11.2 mg, 0.10 mmol, 10 mol%）, 5 milliliters of toluene, magneton stirring is then added.Thereafter it is separately added into
N-hexyl alcohol (102.0 mg, 1.0mmol) and aniline (111.6 mg, 1.2mmol).It will be heated in oil bath after the glass seal of tube
To 120 oC, it is stirred overnight.24 hours postcoolings are reacted to room temperature, solvent under reduced pressure are distilled, crude product passes through silica gel post separation
（Eluant, eluent：Ethyl acetate/hexane：1：5）.Yield：149 milligrams（84%）.
The general formula of the cobalt complex (catalyst) is:
Wherein R3 represents carbon atom number as 1~5 alkyl group, function base, phenyl, heterocycle and substituted heterocyclic radical.
Following synthesis for cobalt complex (catalyst)：
Under room temperature, in 25 milliliters of round-bottomed flasks, by 2,2 ';6 ', 2 ' '-terpyridyl（233 mg, 1 mmol）
It is dissolved in tetrahydrofuran THF（10mL）In, cobalt chloride is then added（129 mg, 1 mmol）.After acquired solution is stirred overnight,
Filtering, after gained light green solid is washed with THF, dry sterling.Yield：318 milligrams（88%）.
Claims (1)
1. a kind of method of synthesis secondary amine, it is characterised in that include the following steps：Under the protection of nitrogen or argon gas, by 0.05-
In nonpolar solvent of the room-temperature dissolution in 5mg, magneton stirring divides thereafter for 0.4mol cobalt complexes and 0.8-1.5mol additives
Not Jia Ru 8-12mol primary alconols and 11-13mol primary amine, 120 oC will be heated in oil bath after the glass seal of tube, be stirred overnight,
24 hours postcoolings are reacted to room temperature, solvent under reduced pressure are distilled, crude product passes through silica gel post separation, as secondary amine derivative；Institute
The general formula for stating cobalt complex catalyst is:
Wherein R3 represents carbon atom number as 1~5 alkyl group, phenyl, heterocycle and substituted heterocyclic radical；The conjunction of cobalt complex
It is at method：Under room temperature, in 25 milliliters of round-bottomed flasks, by 10mol 2,2 ';6 ', 2 ' '-terpyridyl is dissolved in
In 10mL THF, 10mol cobalt chlorides are then added, after acquired solution is stirred overnight, filtering, gained light green solid is washed with THF
After washing, dry sterling is cobalt complex;The primary alconol is benzyl alcohol, 4- methoxy benzyl alcohols or n-hexyl alcohol;Primary amine is
Aniline or 4- aminoanisoles;The additive can be potassium tert-butoxide or sodium tert-butoxide.
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