CN107827764A - A kind of preparation method of double β amino ketones or double β amino esters - Google Patents

Abstract

The invention discloses a preparation method of bis-β-amino ketone or bis-β-amino ester compound. It is obtained by mixing and stirring β-diketone or β-ketoester and diamine compound in proportion, adding catalyst ethanolamine acetate ionic liquid, stirring at room temperature for 3-6 hours, and suction filtration and purification after the reaction is completed. The catalyst obtained by extracting and separating the filtrate in the present invention can be recycled. The beneficial effect of the invention is that the catalyst is easy to prepare, less polluted, no solvent is used in the reaction, the preparation process is simple to operate, the post-reaction treatment is simple, and the catalyst is environmentally friendly. The yield of the product is high and can reach 70-88%.

Description

A kind of preparation method of double beta-amino ketone or double beta-amino esters

technical field

The invention relates to a preparation method of bis-β-amino ketone or bis-β-amino ester, which belongs to the technical field of organic synthesis.

Background technique

As a "clean" solvent and a new catalytic system, ionic liquid (IL) is being accepted and concerned by the catalysis circles and petrochemical enterprises all over the world.

β-amino ketones or β-amino esters are an important class of biologically active substances, which have various biological activities such as antitussive, antibacterial, anti-inflammatory, anti-cancer, anti-viral, sedative, analgesic, antihypertensive, edema-inhibiting, and anti-coagulant. The synthesis of such compounds mostly uses supported solid acids as catalysts. Most of the catalysts are relatively expensive, the preparation process is relatively complicated, and it is difficult to recycle and easily pollute the environment.

Contents of the invention

The technical problem to be solved by the present invention is to provide a new method for catalyzing the synthesis of bis-beta-amino ketones or bis-beta-amino esters using an ionic liquid that is cheap, less polluting to the environment, and easy to prepare and recycle as a catalyst. The method of the invention is simple and the product yield is high.

The technical solution adopted in the present invention is specifically introduced as follows.

A preparation method of bis-β-amino ketone or bis-β-amino ester compound, using β-diketone or β-ketoester and diamine compound as raw materials, using ethanolamine acetate ionic liquid as catalyst, and stirring at room temperature for 3 -6h, after the reaction, filter and purify to obtain the corresponding bis-β-amino ketone or bis-β-amino ester compound.

In the present invention, the structures of β-diketone and β-ketoester are shown in formula II and formula III respectively:

Wherein: R ₂ is selected from any of C ₁ -C ₈ alkyl, phenyl or substituted phenyl; R ₃ is selected from any of C ₁ -C ₆ alkyl.

In the present invention, R ₂ is selected from any one of methyl, 3-phenyl, 4-phenyl, 5-phenyl or 4-methyl; R ₃ is methyl or ethyl;

In the present invention, the structure of the diamine compound is as shown in formula I:

Wherein: R1 is -CH ₂ -)n- or C ₆ H ₄ -, wherein n=2,3,4,5; m=1,2.

In the present invention, R1 is -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, -C ₆ H ₄ -, or -C ₆ H ₄ C ₆ H ₄ -.

In the present invention, the amount of catalyst used is 15%-22% of the diamine compound moles.

In the present invention, the method of recrystallization is adopted for purification, and the solvent used for recrystallization is absolute ethanol.

In the present invention, equal volumes of ethyl acetate and water are added to the filtrate after recrystallization, and after layering, the liquid in the water layer is concentrated and recovered to obtain ethanolamine acetate ionic liquid, which is recycled as a catalyst.

In the present invention, the ethanolamine acetate ionic liquid is composed of ethanolamine quaternary ammonium cation and acetate anion.

Among the present invention, take β-diketone as raw material, the reaction equation of the preparation method of double β-amino ketone is as follows:

Compared with the prior art, the beneficial effects of the present invention are:

The catalyst ethanolamine acetate ionic liquid used in the preparation process of the present invention is liquid at normal temperature and is composed of ethanolamine quaternary ammonium cations and acetate anions. The ionic liquid has acidity and thermal stability, low vapor pressure, easy preparation, less pollution, simple operation in the reaction process, no solvent is used, while avoiding the use of highly corrosive _H2SO4 , etc., the post _- reaction treatment is simple and environmentally friendly. The yield of the product is high and can reach 70-88%.

Description of drawings

Fig. 1 is a ¹ H NMR chart of 1,4-phenylenediamine acetylacetonate obtained in Example 1.

Fig. 2 is a ¹ H NMR chart of diacetylacetonate benzidine obtained in Example 2.

Detailed ways

The present invention will be described in further detail below through specific examples, but the present invention is not limited.

Example 1

A kind of preparation method of bis-beta-aminoketone acetylacetonate 1,4-phenylenediamine, comprises the steps:

(1), put 2.5mmol acetylacetone, 1mmol 1,4-phenylenediamine in a 25mL round bottom flask, shake well;

(2), then add 0.2mmol ionic liquid ethanolamine acetate (self-made, preparation method see Victor HA, Silvana M, Manuel MP, Martin A, Miguel I (2011) J Chem Thermoyn 43:997) in the round bottom flask, Stir the reaction at room temperature for 3h;

(3), after the reaction in step (2), the crude product was obtained by suction filtration, and the crude product was recrystallized with absolute ethanol to obtain pure 1,4-phenylenediamine acetylacetonate; the total yield was 75%, mp.114.3 ~115.2°C; 5 mL of water and 5 mL of ethyl acetate were successively added to the filtrate, and after the liquid was separated, the ethanolamine acetate ionic liquid in the water layer was concentrated and recovered for reuse (recovery rate, 99%).

A Buker AM-500 (500M) nuclear magnetic resonance instrument was used, with TMS as the internal standard and CDCl ₃ as the solvent. Fig. 1 is the nuclear magnetic spectrogram of embodiment 1, and the nuclear magnetic spectrum data of measured product are as follows: ¹ H NMR (500MHz, CDCl ₃ ) δ: 12.57 (s, 2H, NH), 7.58-7.56 (d, 4H, Ar- H), 7.21-7.19 (d, 4H, Ar-H), 5.24 (s, 2H, CH=), 2.14 (s, 6H, _CH3 ), 2.08 (s, 6H, _CH3 ). It was proved that the product was 1,4-phenylenediamine acetylacetonate.

Example 2

A preparation method for bis-beta-aminoketone diacetylacetonate benzidine, comprising the steps of:

(1), put 2.5mmol acetylacetone, 1mmol benzidine in a 25mL round bottom flask, shake well;

(2), then add 0.2mmol ionic liquid ethanolamine acetate to the round bottom flask, stir and react at room temperature for 4h;

(3) After the reaction in step (2), the crude product was obtained by suction filtration, and the crude product was recrystallized with absolute ethanol to obtain pure diacetylacetonate benzidine; the total yield was 78%, mp.115.0～116.8°C; 5mL of water and 5mL of ethyl acetate were successively added to the filtrate, and after the liquid was separated, the ethanolamine acetate ionic liquid in the water layer was concentrated and recovered for reuse; a Buker AM-500 (500M) nuclear magnetic resonance instrument was used, with TMS as the internal Standard, CDCl ₃ as solvent. Fig. 2 is the nuclear magnetic spectrogram of embodiment 2, and the nuclear magnetic spectrum data of measured product is as follows: δ: 12.57 (2H, s, NH), 7.58-7.56 (4H, d, Ar-H), 7.21-7.19 (4H, d, Ar-H), 5.24 (2H, s, CH=), 2.14 (6H, s, CH ₃ ), 2.08 (6H, s, CH ₃ ) prove that the product is diacetylacetonate benzidine.

Example 3

A preparation method of bis-β-aminoketone bis-1-phenyl-1,3-butanedione ethylenediamine, comprising the steps of:

(1), put 2.5mmol 1-phenyl-1,3-butanedione and 1mmol ethylenediamine in a 25mL round bottom flask, and shake well;

(2), then add 0.2mmol ionic liquid ethanolamine acetate to the round bottom flask, stir and react at room temperature for 5h;

(3), after the reaction in step (2), the crude product was obtained by suction filtration, and the crude product was recrystallized with absolute ethanol to obtain pure bis-1-phenyl-1,3-butanedione ethylenediamine; the total yield 82%, mp.182.7～182.9°C; add water and ethyl acetate successively to the filtrate, and after the liquid is separated, concentrate and recycle the ethanolamine acetate ionic liquid in the water layer; adopt Buker AM-500 (500M ) nuclear magnetic resonance apparatus, with TMS as internal standard, CDCl ₃ as solvent. The NMR data of the measured product are as follows: δ: 11.579 (s, 2H, NH), 7.88-7.87 (d, 4H, Ar-H), 7.44-7.42 (m, 6H, Ar-H), 5.73 (s, 2H, CH=), 3.61-3.60 (t, 4H, J=3HZ, CH ₂ -), 2.097 (s, 6H, CH ₃ -). It was proved that the product was bis-1-phenyl-1,3-butanedione ethylenediamine.

Example 4

A preparation method of bis-β-aminoketone bis-1-phenyl-1,3-butanedione propylenediamine, comprising the steps of:

(1), put 2.5mmol 1-phenyl-1,3-butanedione and 1mmol propylenediamine in a 25mL round bottom flask, and shake well;

(2), then add 0.2mmol ionic liquid ethanolamine acetate into the round bottom flask, stir and react at room temperature for 3h;

(3), after the step (2) reaction finishes, the crude product is obtained by suction filtration, and the crude product is recrystallized with absolute ethanol to obtain pure product bis-1-phenyl-1,3-butanedione propylenediamine; total yield 76%, mp.86.0～88.8°C; 5mL water and 5mL ethyl acetate were successively added to the filtrate, and after the liquid was separated, the ethanolamine acetate ionic liquid in the water layer was concentrated and recovered for reuse; BukerAM-500( 500M) nuclear magnetic resonance instrument, with TMS as internal standard, CDCl ₃ as solvent. The NMR data of the measured product are as follows: δ: 11.55 (s, 2H, NH), 7.88-7.87 (d, 4H, Ar-H), 7.45-7.41 (m, 6H, Ar-H), 5.73 (s, 2H, CH=), 3.54-3.53 (m, 4H, J=3HZ, CH ₂ -), 2.12 (s, 6H, CH ₃ -), 2.06-2.04 (m, 2H, CH ₂ -). It was proved that the product was bis-1-phenyl-1,3-butanedione propylenediamine.

Example 5

A preparation method of diacetylacetonate ethylenediamine, comprising the steps of:

(1), put 2.5mmol acetylacetone and 1mmol ethylenediamine in a 25mL round bottom flask, shake well;

(2), then add 0.2mmol ionic liquid ethanolamine acetate into the round bottom flask, stir and react at room temperature for 3h;

(3) After the reaction in step (2), the crude product was obtained by suction filtration, and the crude product was recrystallized with absolute ethanol to obtain pure diacetylacetonate ethylenediamine; the total yield was 88%, mp.110.2～110.5°C Add 5mL water and 5mL ethyl acetate successively in the filtrate, after liquid layering, the ethanolamine acetate ionic liquid in the water layer is concentrated and recycled; adopt Buker AM-500 (500M) NMR instrument, take TMS as Internal standard, CDCl ₃ as solvent. The NMR data of the measured product are as follows: δ: 10.916 (2H, s, NH), 5.018 (2H, s, CH=), 3.450-3.438 (4H, t, CH ₂ -), 2.023 (6H, s, CH ₃ -), 1.929 (6H, s, CH ₃ -) proves that the product is diacetylacetonate ethylenediamine.

Example 6

A preparation method of methyl diacetoacetate ethylenediamine, comprising the steps of:

(1), put 2.5mmol methyl acetoacetate, 1mmol ethylenediamine in a 25mL round bottom flask, shake well;

(2), then add 0.2mmol ionic liquid ethanolamine acetate to the round bottom flask, stir and react at room temperature for 6h;

(3), after the reaction of step (2), the crude product was obtained by suction filtration, and the crude product was recrystallized with absolute ethanol to obtain pure product methyl diacetoacetate ethylenediamine; the total yield was 70%, mp.137.2～ 137.5°C; water and ethyl acetate were added successively to the filtrate, and after the liquid was separated, the ethanolamine acetate ionic liquid in the water layer was concentrated and recovered for reuse; a Buker AM-500 (500M) nuclear magnetic resonance instrument was used, and TMS was used as the Internal standard, CDCl ₃ as solvent. The NMR data of the measured product are as follows: δ: 8.65 (2H, s, NH), 4.52 (2H, s, CH=), 3.64 (6H, s, CH ₃ -), 3.39-3.38 (4H, m, CH ₂ -), 1.94 (6H,s, CH ₃ -). It was proved that the product was ethylenediamine diacetoacetate methyl ester.

Example 7

The ethanolamine acetate ionic liquid that adopts reclaiming in embodiment 1 is catalyst, a kind of preparation method of bis-beta-aminoketone acetylacetonate 1,4-phenylenediamine, comprises the following steps:

(1), put 2.5mmol acetylacetone, 1mmol 1,4-phenylenediamine in a 25mL round bottom flask, shake well;

(2), then add the ionic liquid ethanolamine acetate that reclaims among the embodiment 1 in the round-bottomed flask, stir and react at room temperature for 3h;

(3) After the reaction in step (2), the crude product was obtained by suction filtration, and the crude product was recrystallized with absolute ethanol to obtain pure 1,4-phenylenediamine acetylacetonate, with a yield of 74.8%, mp.114.3～115.2 ℃; 5mL water and 5mL ethyl acetate were successively added to the filtrate, and after the liquid was separated, the ethanolamine acetate ionic liquid in the water layer was concentrated and recovered for reuse. Around 75%.

The specific embodiments above are only used to illustrate the present invention, rather than to limit the present invention. Within the spirit of the present invention and the scope of claims, any modifications and changes made to the present invention will fall within the protection scope of the present invention.

Claims (9)

1. the preparation method of a kind of double beta-amino ketones or double beta-amino ester type compounds, it is characterised in that with beta-diketon or β -one Ester and diamine compound are raw material, using monoethanolamine acetate ion liquid as catalyst, reaction 3-6h are stirred at room temperature, reaction terminates Afterwards, filter, purify, obtain corresponding double beta-amino ketones or double beta-amino ester type compounds.

2. preparation method according to claim 1, it is characterised in that the structure of beta-diketon and 'beta '-ketoester respectively such as Formula II and Shown in formula III：

Wherein：R₂Selected from C₁~C₈It is any in alkyl, phenyl or substituted-phenyl；R₃Selected from C₁~C₆Alkyl is any.

3. preparation method according to claim 1, it is characterised in that R₂Selected from methyl, 3- phenyl, 4- phenyl, 5- phenyl or It is any in 4- methyl；R₃For methyl or ethyl.

4. preparation method according to claim 1, it is characterised in that the structure of diamine compound is shown in formula I：

Wherein：R1 is-CH₂-) n- or C₆H₄-, wherein n=2,3,4,5；M=1,2.

5. preparation method according to claim 1, it is characterised in that R1 is selected from-CH₂CH₂-,-CH₂CH₂CH₂-,-C₆H₄-, Or-C₆H₄C₆H₄-。

6. preparation method according to claim 1, it is characterised in that catalyst amount is diamine compound molal quantity 15%~22%.

7. preparation method according to claim 1, it is characterised in that purify and use means re-crystallization, it is molten used in recrystallization Agent is absolute ethyl alcohol.

8. preparation method according to claim 7, it is characterised in that isometric acetic acid second is added in the filtrate after recrystallization Ester and water, after being layered, after the liquid concentration recovery in water layer, monoethanolamine acetate ion liquid is obtained, as catalyst Recycle.

9. preparation method according to claim 1, it is characterised in that monoethanolamine acetate ion liquid is by monoethanolamine season Ammonium cation forms with acetic acid anion.