CN105622569A

CN105622569A - O-hydroxyaniline derivative and preparation method thereof

Info

Publication number: CN105622569A
Application number: CN201610070495.4A
Authority: CN
Inventors: 余娟; 胡益民
Original assignee: Anhui Normal University
Current assignee: Anhui Normal University
Priority date: 2016-01-29
Filing date: 2016-01-29
Publication date: 2016-06-01
Anticipated expiration: 2036-01-29
Also published as: CN105622569B

Abstract

The invention discloses an o-hydroxyaniline derivative and a preparation method thereof. Compared with the prior art, the invention provides a synthetic method of an o-hydroxyaniline derivative to generate a series of novel o-hydroxyaniline derivatives. Compared with existing o-hydroxyaniline derivatives, the o-hydroxyaniline derivative prepared by the invention is polycyclic, has more complex and diversified structure that is more complex and diversified, prevails among pharmaceutical intermediates, functional materials and farmland pharmaceuticals, is widely applied in the fields such as molecular machinery, materials chemistry and supramolecular chemistry, and also has a more promising application prospect in chemical production and clinical medicine; moreover, the preparation method provided by the invention is simple and is high in synthetic efficiency.

Description

A kind of o-hydroxy amine derivative and preparation method thereof

Technical field

The invention belongs to organic synthesis field, be specifically related to a kind of o-hydroxy amine derivative and preparation method thereof.

Background technology

At present, aminated compounds is of many uses, and the amino in organic compound turns to other groups by diazo-reaction is variable, is important Organic Chemicals. Can synthetic pesticide, dyestuff and multiple organic and fine chemical material and the intermediate such as pigment, medicine, rubber chemicals, synthetic resin, textile auxiliary, surfactant, sensitive material by amine.

The introducing of amino and the function of fine chemicals are it occur frequently that relation. The introducing of such as amino may result in compound Red Shift Phenomena in the visible spectrum, and this has important function in dyestuff chemistry. Introducing amino at the ortho position of the chromophore of dyestuff can make darkening of dyestuff dimmed, and the introducing of amino simultaneously can change the printing and dyeing performance of dyestuff. In organic molecule, generally introduce amino will cause the change of compound physiologically active, and many compounds with specific physiologically active can be found out. Amino-compound, particularly aminoacid etc. play a part particular importance in life process.

In synthesis chemistry, an important sources of aniline and its derivatives is nitrates of aromatic hydrocarbons reduction. The reduction of nitro mainly has following several method: (1) stoichiometry reducing process, wherein mainly has the reducing processs such as iron powder, zinc powder and akali sulphide; (2) catalytic hydrogenation method, conventional catalyst is the noble metals such as ruthenium, palladium, platinum; (3) non-hydrogen catalytic reduction method, conventional reducing agent has CO, hydrazine etc.; (4) electrochemical reducing.

Anil is ubiquity in many pharmaceutical intermediates, functional material and farmland medicine. All the time, chemist always searches for novel effective route of synthesis. At first, under transition metal-catalyzed, aromatic coupling reaction the research generating corresponding anil has been achieved with very big progress. But it is no matter the use of reaction substrate or catalyst, all lacks economic benefit. Until recent decades, occur in that by the aerobic catalytic reaction of non-aromatic compounds, just further improve this type of reaction, but this kind of report overwhelming majority still uses the noble metal such as palladium, ruthenium as catalyst.

And discovered in recent years copper and non-metallic catalyst also catalytic reaction can generate corresponding aniline compound. Relatively conventional noble metal catalyst, this type of reaction system, not only toxic and side effects is little, and less costly.

But, in prior art, amino benzenes compounds synthetic method is complicated, and efficiency is low.

Summary of the invention

For solving above-mentioned technical problem, the present invention provides a kind of o-hydroxy amine derivative, has multi-ring existence, and structure is more complicated various to be widely used in pharmaceutical intermediate, functional material and farmland medicine.

The preparation method that present invention also offers a kind of o-hydroxy amine derivative, method is simple, efficient.

A kind of o-hydroxy amine derivative provided by the invention, its structural formula is:

Described E₁=E₂=CO₂R; R is straight chained alkyl, branched alkyl; R₁��R₂For hydrogen, phenylacetylene base and its corresponding derivant.

Further, described R is ethyl, R₁��R₂For hydrogen; Its structural formula is

The preparation method of a kind of o-hydroxy amine derivative provided by the invention, comprises the following steps:

(1) with sodium hydride for catalyst, diethyl malonate and propargyl bromide joining ice-water bath in anhydrous acetonitrile, stirring reaction 8 hours, product purification separates, and obtains white solid product, i.e. compound 1;

(2) compound 1 and phenylacetylene base bromine are blended in Pd (PPh₃)₂Cl₂In the anhydrous and oxygen-free catalyst system and catalyzing of/CuI, making alkali with triethylamine, with anhydrous acetonitrile for solvent, under room temperature, at least stirring reaction 12 hours, product purification separation, obtains light tan solid product, i.e. precursor compound 2;

(3) when 100 DEG C-120 DEG C, precursor compound 2 prepared by step (2) reacts 8-12 hour with oxime in toluene, and product purification separates, and obtains tan crystals, i.e. o-hydroxy amines.

Further, in step (1), sodium hydride, diethyl malonate and propargyl bromide mol ratio are 4.0-4.4:1:2.2-3.2; Diethyl malonate concentration in anhydrous acetonitrile is 0.4-0.8mol/L;

Further, described in step (1), purifies and separates is particularly as follows: product adds water washing, is extracted with ethyl acetate, and decompression is spin-dried for, by the ethyl acetate of volume ratio 1:100: petroleum ether=1:100 column chromatography for separation; Obtain white solid product, i.e. compound 1;

Further, compound 1 described in step (2) and phenylacetylene base bromine, Pd (PPh₃)₂Cl₂, triethylamine amount of substance be 1:2.2-3.2:0.008-0.014:4-5; The compound 1 concentration in anhydrous acetonitrile is 0.30-0.60mol/L.

Further, Pd (PPh described in step (2)₃)₂Cl₂In the anhydrous and oxygen-free catalyst system and catalyzing of/CuI, mol ratio Pd (PPh₃)₂Cl₂: CuI=3:1;

Further, described in step (2), purifies and separates is particularly as follows: wash with water, is extracted with ethyl acetate, and decompression is spin-dried for, by the ethyl acetate of volume ratio 1:100: petroleum ether column chromatography for separation, obtains light tan solid product, i.e. precursor compound 2;

In step (3), the amount ratio of precursor compound 2 and oxime is 1:1-1.5; Precursor compound 2 concentration in toluene is 0.2-0.5mol/L.

Further, purifies and separates described in step (3) is particularly as follows: products in water washing, and extraction into ethyl acetate, column chromatography is crystallizing at room temperature again, produces and obtains tan crystals by petroleum ether, be i.e. o-hydroxy amines.

Compared with prior art, the invention provides the synthetic method of a kind of brand-new o-hydroxy amine derivative, generate a series of new o-hydroxy amine derivative. Relative to existing o-hydroxy amine derivative, o-hydroxy amine derivative prepared by the present invention has multi-ring existence, its structure is more complicated various, its structure is more complicated various, ubiquity in pharmaceutical intermediate, functional material and farmland medicine, it is widely used in many fields such as molecule machine, materials chemistry and supramolecular chemistry, in Chemical Manufacture, clinical medicine, also also will show more wide purposes prospect simultaneously. And, preparation method provided by the invention is simple, and combined coefficient is high.

Accompanying drawing explanation

Fig. 1 a is the structural formula of o-hydroxy amines;

Fig. 1 b is the structural formula of preferred o-hydroxy amines;

Fig. 2 a is the proton nmr spectra of the o-hydroxy amines of embodiment 1 preparation;

Fig. 2 b is the carbon-13 nmr spectra of the o-hydroxy amines of embodiment 1 preparation.

Detailed description of the invention

Embodiment 1

A kind of o-hydroxy amine derivative, its structural formula is:

The preparation method of a kind of o-hydroxy amine derivative, comprises the following steps:

(1) with 820mmol sodium hydride for catalyst, 200mmol diethyl malonate and 440mmol propargyl bromide are joined ice-water bath in 250mL anhydrous acetonitrile, stirring reaction 8 hours, product adds water washing, being extracted with ethyl acetate, decompression is spin-dried for, by the ethyl acetate of volume ratio 1:100: petroleum ether column chromatography for separation, obtain white solid product, i.e. compound 1;

(2) 80mmol compound 1 and 200mmol phenylacetylene base bromine are blended in 1.09mmolPd (PPh₃)₂Cl₂In the anhydrous and oxygen-free catalyst system and catalyzing of/CuI, mol ratio Pd (PPh₃)₂Cl₂: CuI=3:1, alkali is made with 340mmol triethylamine, with 200ml anhydrous acetonitrile for solvent, stirring reaction 12 hours under room temperature, products in water washs, and is extracted with ethyl acetate, decompression is spin-dried for, by the ethyl acetate of volume ratio 1:100: petroleum ether column chromatography for separation, obtain light tan solid product, i.e. precursor compound 2;

(3) when 100 DEG C, the 0.445g precursor compound 2 prepared by step (2) reacts 12 hours with 0.211g oxime in 3mL toluene, obtains compound 3, i.e. the crude product of o-hydroxy amines; Being washed by the crude product with water of hydroxyanilines compound, extraction into ethyl acetate, crystallizing at room temperature, produce and obtain tan crystals and o-hydroxy amines by petroleum ether, productivity is about 65.3%.

Tan crystals product structure passes through;¹HNMR;¹³CNMR measures.

Tan crystals product:

¹HNMR(500MHz,CDCl₃) �� 7.58 (d, 2H), 7.54 (m, 2H), 7.52 (q, 2H), 7.40 (m, 3H), 7.39 (m, 1H), 7.34-7.27 (m, 2H),, 7.19-7.13 (t, 2H), 4.19 (q, 4H), 3.45 (s, 4H), 1.28-1.24 (t, 6H) 0.97-0.94 (t, 2H).

¹³CNMR(125MHz,CDCl3)��147.06,138.36,132.88,132.85,131.42,131.23,131.17,129.56,127.58,127.55,126.3��

Claims

1. an o-hydroxy amine derivative, it is characterised in that the structural formula of described o-hydroxy amine derivative is:

2. o-hydroxy amine derivative according to claim 1, it is characterised in that described R is ethyl, R₁��R₂For hydrogen.

3. the preparation method of an o-hydroxy amine derivative, it is characterised in that described preparation method comprises the following steps:

4. preparation method according to claim 3, it is characterised in that in step (1), sodium hydride, diethyl malonate and propargyl bromide mol ratio are 4.0-4.4:1:2.2-3.2.

5. the preparation method according to claim 3 or 4, it is characterised in that diethyl malonate concentration in anhydrous acetonitrile is 0.4-0.8mol/L.

6. preparation method according to claim 3, it is characterised in that compound 1 described in step (2) and phenylacetylene base bromine, Pd (PPh₃)₂Cl₂, triethylamine amount of substance be 1:2.2-3.2:0.008-0.014:4-5.

7. the preparation method according to claim 3 or 6, it is characterised in that described in step (2), the compound 1 concentration in anhydrous acetonitrile is 0.30-0.60mol/L.

8. the preparation method according to claim 3 or 6, it is characterised in that Pd (PPh described in step (2)₃)₂Cl₂In the anhydrous and oxygen-free catalyst system and catalyzing of/CuI, mol ratio Pd (PPh₃)₂Cl₂: CuI=3:1.

9. preparation method according to claim 3, it is characterised in that in step (3), the amount ratio of precursor compound 2 and oxime is 1:1-1.5.

10. the preparation method according to claim 3 or 6, it is characterised in that in step (3), precursor compound 2 concentration in toluene is 0.2-0.5mol/L.