CN104592314B - Ferrocene 7-naphthyridine derivatives and its synthetic method and application - Google Patents

Abstract

The invention provides two kinds of ferrocene 7-naphthyridine derivatives and its synthetic method, wherein, ferrocene single armed 7-naphthyridine derivatives FeL3 and ferrocene both arms 7-naphthyridine derivatives FeL4 can be respectively used to Cr³⁺Detection.

Description

Ferrocene 7-naphthyridine derivatives and its synthetic method and application

Technical field

The present invention relates to the detection probe of heavy metal ion, more particularly to a kind of ferrocene derivatives and its synthetic method and Using.

Background technology

Metal ion is widely distributed in natural environment and organism, is played an important role in vital movement, while golden Category ionic environment pollution is also the emphasis of countries in the world concern.Chromium has very strong enrichment, can excessively make one poisoning.Therefore How effectively to detect chromium ion for suffering from significance in environmental science, bioscience and medical science.Ferrocene-Derived Thing has stronger cell bio-activity, can suppress growth of cancer cells, be expected to develop into new cancer therapy drug, simultaneously because two cyclopentadienyls Iron and its derivative are easily chemically modified, therefore ferrocene derivatives have very big advantage as metal ion probe.

The content of the invention

In view of this, it is of the invention be to provide a kind of ferrocene 7-naphthyridine derivatives that can be used as metal ion probe and its Synthetic method and application.

One aspect of the present invention provides a kind of ferrocene 7-naphthyridine derivatives, and its chemical structural formula is：

Ferrocene single armed 7-naphthyridine derivatives FeL3.

Second aspect of the present invention provides the synthetic method of the ferrocene single armed 7-naphthyridine derivatives FeL3, and it includes：Will Ferrocene carboxaldehyde is obtained under sodium triacetoxy borohydride effect with the reaction of 2- methyl -7- amino -1,8 naphthyridines.

Third aspect present invention provides a kind of ferrocene 7-naphthyridine derivatives, and its chemical structural formula is：

Ferrocene both arms 7-naphthyridine derivatives FeL4.

Fourth aspect present invention provides the synthetic method of the ferrocene both arms 7-naphthyridine derivatives FeL4, and it includes：Will Ferrocene derivatives FecDN is in LiAlH₄Under effect, reaction is obtained.

Fifth aspect present invention provides above two ferrocene 7-naphthyridine derivatives in Cr³⁺Detection in application.

The beneficial effects of the invention are as follows：The invention provides ferrocene 7-naphthyridine derivatives FeL3 and FeL4 and its preparation side Method, it may be respectively used in Cr³⁺Detection.

Brief description of the drawings

Fig. 1 is the ultraviolet titration curve figure of embodiment three；

Fig. 2 is the ultraviolet titration curve figure of example IV；

Fig. 3 is the ultraviolet titration curve figure of embodiment five；

Fig. 4 schemes for the nucleus magnetic hydrogen spectrum titration of embodiment six.

Embodiment

One aspect of the present invention provides a kind of ferrocene 7-naphthyridine derivatives, and its chemical structural formula is：

Ferrocene single armed 7-naphthyridine derivatives FeL3.

Second aspect of the present invention provides the synthetic method of the ferrocene single armed 7-naphthyridine derivatives FeL3, and it includes：Will Ferrocene carboxaldehyde is obtained under sodium triacetoxy borohydride effect with the reaction of 2- methyl -7- amino -1,8 naphthyridines.

Ferrocene single armed 7-naphthyridine derivatives FeL3 preparation course of reaction is as follows：

It is preferred that, the preparation method of the ferrocene single armed 7-naphthyridine derivatives FeL3 comprises the following steps：

A) ferrocene carboxaldehyde and the naphthyridines of 2- methyl -7- amino -1,8 are dissolved in dry CH₂Cl₂；

B) sodium triacetoxy borohydride is added；

C) triethylamine is added, regulation pH is 5-6；

D) heated overnight at reflux, reaction is cooled down after terminating, and revolving removes CH₂Cl₂Dissolution residual substance obtains orange/yellow solid Crude product；

E) silica gel column chromatography is purified, and yellow-white foaming solid is obtained after drying.

Third aspect present invention provides a kind of ferrocene 7-naphthyridine derivatives, and its chemical structural formula is：

Ferrocene both arms 7-naphthyridine derivatives FeL4.

Fourth aspect present invention provides the synthetic method of the ferrocene both arms 7-naphthyridine derivatives FeL4, and it includes：Will Ferrocene derivatives FecDN is in LiAlH₄Under effect, reaction is obtained.

Ferrocene both arms 7-naphthyridine derivatives FeL4 preparation course of reaction is as follows：

It is preferred that, the preparation method of the ferrocene both arms 7-naphthyridine derivatives FeL4 comprises the following steps：

A) by C₃₀H₂₄FeN₆O₂Dry tetrahydrofuran solution be added drop-wise in the tetrahydrofuran suspension of lithium aluminium hydride reduction；

B) heated overnight at reflux, reaction is cooled down after terminating, and unnecessary hydrogen is quenched in stirring, the aqueous ammonium chloride solution that saturation is added dropwise Change aluminium lithium, extraction, dry organic phase, filtering revolving obtain crude yellow solid；

C) silica gel column chromatography is purified, and yellow solid pure products are obtained after drying.

Fifth aspect present invention provides above two ferrocene 7-naphthyridine derivatives in Cr³⁺Detection in application.Specifically , on the one hand, Cr can be detected using ultraviolet spectrophotometry³；On the other hand, also Cr can be detected using nuclear-magnetism titration³.It is preferred that , the nuclear-magnetism titration is carried out in deuterated methanol and DMSO-d6 mixed solutions.

Synthetic method and its application of the ferrocene 7-naphthyridine derivatives of the present invention are discussed in detail below in conjunction with specific embodiment.

Embodiment one

Ferrocene single armed 7-naphthyridine derivatives FeL3 synthesis

0.15mmol ferrocene carboxaldehydes and the stirring of the naphthyridines of 0.21mmol 2- methyl -7- amino -1,8 are dissolved in into 25ml to dry CH₂Cl₂, 0.75mmol sodium triacetoxy borohydrides are added, it is 5-6 to adjust pH with triethylamine, is heated to reflux night, is cooled to Room temperature, revolving, CH₂Cl₂Dissolution residual substance uses saturation NaHCO successively₃Solution, saturation NaCl solution, H₂O washs organic phase, anhydrous Na₂SO₄Dry, filtering revolving obtains orange/yellow solid crude product, uses CH₂Cl₂/CH₃OH=20:1 (v/v) is used as eluent, silicon It is gel column chromatography eluting, 28mg yellow-white foaming solid pure products are obtained after vacuum drying.

Embodiment two

Ferrocene both arms 7-naphthyridine derivatives FeL4 synthesis

By the C that 10ml concentration is 0.09mmol₃₀H₂₄FeN₆O₂It is 2.7mmol's that tetrahydrofuran solution, which is added drop-wise to 10ml concentration, In lithium aluminium hydride reduction tetrahydrofuran suspension, wherein, the C₃₀H₂₄FeN₆O₂Chemical structural formula is：

Heated overnight at reflux, reactant mixture is cooled to room temperature, opens wide and is stirred vigorously under system, and the ammonium chloride of saturation is added dropwise Unnecessary lithium aluminium hydride reduction is quenched in the aqueous solution, uses CH₂Cl₂Repeatedly extraction, anhydrous Na₂SO₄Organic phase is dried, filtering revolving obtains Huang Color solid crude product FeL4, uses CH₂Cl₂/CH₃OH=15:1 (v/v) is used as eluent, silica gel column chromatography purifying, after vacuum drying Obtain 26.0mg yellow solid pure products.

The novel ferrocene 7-naphthyridine derivatives FeL3-4 of 1-2 of embodiment of the present invention synthesis passes through¹H NMR,¹³C { H } NMR and MS means have carried out Structural Identification, it was demonstrated that its structure is indicated by above structural formula.

Embodiment three

Ferrocene 7-naphthyridine derivatives FeL3-4 is to Cr³⁺Selectivity interaction

100mM Cu is added dropwise respectively into 10 μM of ferrocene single armed 7-naphthyridine derivatives FeL3 ethanol solution²⁺And 100mM Cr³⁺, sample respectively correspond to marked as A and B；Control the Cu of ion²⁺And Cr³⁺Ultimate density be 0,10,20,40 successively, 60,80,100,120,150,180,200 μM, sample correspondence is marked as English alphabet a to k.Using ultraviolet spectrophotometry, inspection The change for the uv-visible absorption spectroscopy surveyed before and after being added dropwise.Respectively obtain the ultraviolet titration curve as shown in Figure 1A and B.

100mM Cu is added dropwise respectively into 10 μM of ferrocene both arms 7-naphthyridine derivatives FeL4 ethanol solution²⁺And 100mM Cr³⁺, sample respectively correspond to marked as C and D；Control the Cu of ion²⁺And Cr³⁺Ultimate density be 0,10,20,40 successively, 60,80,100,120,150,180,200 μM, sample correspondence is marked as English alphabet a to k.Using ultraviolet spectrophotometry, inspection The change for the uv-visible absorption spectroscopy surveyed before and after being added dropwise, respectively obtains ultraviolet titration curve as shown in figures 1C andd.

Example IV

Hybrid ionic is to ferrocene 7-naphthyridine derivatives FeL3 and FeL4 specific recognition Cr³⁺Interference Detection

13 kinds of hybrid ionics that 100mM is added dropwise into 10 μM of ferrocene single armed 7-naphthyridine derivatives FeL3 ethanol solution are molten Liquid, including：k⁺,Na⁺,Ba²⁺,Mg²⁺,Ca²⁺,Sr²⁺,Zn²⁺,Co²⁺,Ni²⁺,Mn²⁺,Cd²⁺,Hg²⁺,Pd²⁺, control hybrid ionic molten The ultimate density of liquid is 0,100,200,300,400,500,600 μM successively, and sample correspondence is marked as English alphabet a to g；

100mM Cu is added dropwise respectively into 10 μM of ferrocene single armed 7-naphthyridine derivatives FeL3 ethanol solution²⁺And 100mM Cr³⁺, sample respectively correspond to marked as A and B；Control the Cu of ion²⁺And Cr³⁺Ultimate density be 100,200,300 successively, 400,500 μM, sample correspondence is marked as English alphabet h to l；

Using ultraviolet spectrophotometry, detection be added dropwise before and after uv-visible absorption spectroscopy change, respectively obtain as Ultraviolet titration curve shown in Fig. 2A and B.

13 kinds of hybrid ionics that 100mM is added dropwise into 10 μM of ferrocene both arms 7-naphthyridine derivatives FeL4 ethanol solution are molten Liquid, including：k⁺,Na⁺,Ba²⁺,Mg²⁺,Ca²⁺,Sr²⁺,Zn²⁺,Co²⁺,Ni²⁺,Mn²⁺,Cd²⁺,Hg²⁺,Pd²⁺, control hybrid ionic molten The ultimate density of liquid is 0,100,200,300,400,500,600 μM successively, and sample correspondence is marked as English alphabet a to g；

100mM Cu is added dropwise respectively into 10 μM of ferrocene both arms 7-naphthyridine derivatives FeL4 ethanol solution²⁺And 100mM Cr³⁺, sample respectively correspond to marked as C and D；Control the Cu of ion²⁺And Cr³⁺Ultimate density be 100,200,300 successively, 400,500 μM, sample correspondence is marked as English alphabet h to l；

Using ultraviolet spectrophotometry, detection be added dropwise before and after uv-visible absorption spectroscopy change, respectively obtain as Ultraviolet titration curve shown in Fig. 2 C and D.

Embodiment five

Ferrocene 7-naphthyridine derivatives FeL3~FeL4 specific recognitions Cu²⁺And Cr³⁺Practical application

Take respectively 10 μM ferrocene single armed 7-naphthyridine derivatives FeL3, ferrocene both arms 7-naphthyridine derivatives FeL4 ethanol it is molten Liquid, sample is corresponded to marked as A and B respectively, and 50.25mM 15 kinds of hybrid ionic aqueous solution are added dropwise thereto, including：k⁺,Na⁺, Ba²⁺,Mg²⁺,Ca²⁺,Sr²⁺,Zn²⁺,Co²⁺,Ni²⁺,Mn²⁺,Cd²⁺,Hg²⁺,Pd²⁺,Cr³⁺,Cu²⁺, mixed ion solutions in titration Final concentration is 0,50.25,100.5,150.75,201,251.25,301.5,351.75,402,452.25,502.5 μM successively, Sample correspondence is marked as English alphabet a to k.

Using ultraviolet spectrophotometry, the change of the uv-visible absorption spectroscopy before and after detection dropwise addition, ferrocene naphthyridines Derivative FeL3, FeL4 respectively obtain ultraviolet titration curve as shown in figs 3 a andb.

Embodiment six

It is 4 to configure volume ratio:1 deuterated methanol and DMSO-d₆Mixed liquor, ferrocene single armed 7-naphthyridine derivatives FeL3 is molten Solution is in deuterated methanol and DMSO-d₆In mixed liquor, into the ferrocene single armed 7-naphthyridine derivatives FeL3 mixed solutions of same concentration in 0-5 times of Cu is added dropwise successively²⁺, titrated by nuclear-magnetism, obtain nucleus magnetic hydrogen spectrum titration figure as shown in Figure 4.Wherein, 0e, 0.5e and 5e represents concentration of metal ions as 0 times, 0.5 times and 5 times of ferrocene single armed 7-naphthyridine derivatives FeL3 concentration respectively.

As shown in Figure 1, ferrocene 7-naphthyridine derivatives FeL3 and FeL4 is instilling Cu²⁺Afterwards, the absworption peak at derivative 349nm Do not occur significant change, simply absorbance is increased.As addition Cr³⁺Afterwards, absworption peak of the derivative at 349nm there occurs 20nm red shift, is migrated to 369nm, while occurring a new absworption peak at 378nm.

As a result show, ferrocene 7-naphthyridine derivatives FeL3 and FeL4 are only to Cr³⁺There is excellent Selective recognition effect.

Such as Fig. 2, being progressively added dropwise into 10 μM of ferrocene 7-naphthyridine derivatives FeL3 or FeL4 ethanol solution does not include Cu²⁺ And Cr³⁺13 kinds of hybrid ionics, FeL3 and FeL4 ethanol solution has obvious ultraviolet absorption peak at 348nm, when adding 0- After 12 times of hybrid ionic, their UV absorption does not have significant change.After copper ion is added, 348nm UV absorption There are some blue shifts at peak, but obvious not as FeL1 and FeL2, can be neglected.Equally, add after chromium ion, its UV absorption is bent Significant change, 348nm absworption peak red shift 23nm to 371nm occur for line.

As a result show, ferrocene 7-naphthyridine derivatives FeL3 or FeL4 has good Selective recognition to act on to chromium ion, has One obvious variation characteristic is that 348nm absworption peak is substantially migrated to 371nm.

Hybrid ionic in practical application may include copper ion and chromium ion simultaneously.To study this kind of ferrocene derivatives Selectivity in actual complex system, we have prepared 15 kinds of mixed ion solutions including copper ion and chromium ion, Contain k⁺,Na⁺,Ba²⁺,Mg²⁺,Ca²⁺,Sr²⁺,Zn²⁺,Co²⁺,Ni²⁺,Mn²⁺,Cd²⁺,Hg²⁺,Pd²⁺,Cr³⁺,Cu²⁺Deng 15 kinds of mixing Ion.As shown in figure 3, after 15 kinds of hybrid ionics are added dropwise to, for ferrocene naphthyridines single armed derivative FeL3 and ferrocene naphthalene Pyridine both arms derivative FeL4 derivatives, occur in that and obviously change at one, be i.e. a new absworption peak occurs in 371nm or so, Illustrate that ferrocene 7-naphthyridine derivatives FeL3 and FeL4 can only have specific recognition to chromium ion, can be applied to it is actually detected in Go, only by ultraviolet, test limit just can as little as 3.25 μM.

For ferrocene 7-naphthyridine derivatives FeL3 and FeL4, such as Fig. 4 is had found after copper ion and chromium ion is added, naphthyridines Ring hydrogen spectral peak all there occurs small migration to low field, illustrate that metal ion is complexed with the nitrogen in molecule.

The explanation of above example is only intended to the method and its core concept for helping to understand the present invention.It should be pointed out that pair , under the premise without departing from the principles of the invention, can also be to present invention progress for those skilled in the art Some improvement and modification, these are improved and modification is also fallen into the protection domain of the claims in the present invention.

Claims (5)

1. a kind of purposes of ferrocene 7-naphthyridine derivatives, it is characterised in that to Cr³⁺Detection identification application, its chemical structural formula For：

2. a kind of ferrocene 7-naphthyridine derivatives, its chemical structural formula is：

3. the preparation method of ferrocene 7-naphthyridine derivatives as claimed in claim 2, it includes：By ferrocene derivatives FecDN In LiAlH₄Under effect, reaction is obtained.

4. the preparation method of ferrocene 7-naphthyridine derivatives as claimed in claim 2, it comprises the following steps：

A) by C₃₀H₂₄FeN₆O₂Dry tetrahydrofuran solution be added drop-wise in the tetrahydrofuran suspension of lithium aluminium hydride reduction；

B) heated overnight at reflux, reaction is cooled down after terminating, and unnecessary aluminum hydride is quenched in stirring, the aqueous ammonium chloride solution that saturation is added dropwise Lithium, extraction, dry organic phase, filtering revolving obtains crude yellow solid；

C) silica gel column chromatography is purified, and yellow solid pure products are obtained after drying.

5. ferrocene 7-naphthyridine derivatives as claimed in claim 2 are in Cr³⁺Detection in application.