CN111995636B - Ortho-hydroxyl-nitrogen silane compound and synthetic method thereof - Google Patents

Abstract

The invention discloses an o-hydroxy-nitrosilane compound and a synthesis method thereof. The o-hydroxy-nitrosilane compound has the following general chemical formula:

In the formula, Y ₁ -Y ₉ are independently selected from hydrogen atom, halogen atom, C _1-22 hydrocarbon group, C _1-22 haloalkyl group, hydroxyl group, amino group, carbonyl group, amino group, carboxyl group, ester group, cyano group, phenyl group , benzyl or nitro; R ¹ is selected from C _1-22 alkyl. The synthesis method comprises the following steps: taking the salicylidene aniline compound shown in formula II and the alkyl silicon compound shown in formula III as reaction raw materials, and reacting under heating conditions in the presence of a ruthenium catalyst and a solvent to obtain The o-hydroxy-nitrogen silane compound shown in formula I, the reaction formula is as follows:

In the formula, R ¹ is selected from C _1-22 alkyl groups.

Description

A kind of o-hydroxy-nitrosilane compound and its synthesis method

technical field

The invention relates to the technical field of organic chemistry, in particular to an o-hydroxyl-nitrosilane compound and a synthesis method thereof.

Background technique

Organosilicon compounds are valuable synthetic intermediates in various organic reactions and have diverse potential uses in materials science. In addition, there have been increasing reports in the literature recently about the use of organosilicon compounds as therapeutically relevant molecules, such as amilotide, phthalic acid, silicon-containing analogues of tetrahydroisoquinoline, silapropin, and TMS- Application of alanine in medicinal chemistry (J.Am.Chem.Soc.2009,131,8350-8351; Chem.Soc.Rev.2009,38,1002-1010; J.Med.Chem.2013,56,388- 405).

Due to the potential biological activity of organosilicon compounds, they can be used as potential drug molecules in antihypertensive, antitumor, antidepressant and other fields, so they have attracted widespread attention, and the preparation methods of organosilicon compounds have also become a research hotspot. In recent years, the use of noble metals such as palladium as catalysts and silylation through carbon-hydrogen bonds can greatly improve the synthesis efficiency of this type of skeleton compound, reduce the steps of synthesizing related intermediates, and reduce the emission of by-products such as halogenated hydrocarbons. It is a better synthesis strategy for organosilicon compounds. However, the use of palladium catalysts in the current synthetic methods requires the participation of multiple reactants (Chemistry-A European Journal. 2014, 30, 9250), while the use of other existing catalytic systems requires multiple steps, and cannot protect Hydroxyl (Catalysis Science & Technology. 2014, 11, 3964), restricts the universality of the substrate and increases the energy consumption of the synthesis process. Therefore, there is an urgent need to explore an efficient and simple method for synthesizing o-hydroxy-nitrosilane compounds using relatively economical catalysts.

Contents of the invention

The purpose of the present invention is to overcome the defects of the existing preparation technology, and provide an o-hydroxy-nitrosilane compound, which has the characteristics of stable structure, and has application advantages and potential in the fields of new materials, new drug creation and the like.

Another object of the present invention is to provide a synthesis method of o-hydroxyl-nitrosilane compound, which has the advantages of simple raw materials, convenient operation, high yield and suitability for industrial production.

The invention discloses an o-hydroxy-nitrosilane compound, which has the following general chemical formula:

In the formula,

Y ₁ -Y ₉ are independently selected from hydrogen atom, halogen atom, C _1-22 hydrocarbon group, C _1-22 haloalkyl group, hydroxyl group, amino group, carbonyl group, amino group, carboxyl group, ester group, cyano group, phenyl group, benzyl group or nitro;

R ¹ is selected from C _1-22 alkyl groups.

Further, in the formula, the Y ₁ -Y ₉ are independently selected from C _1-10 hydrocarbon groups or C _1-10 haloalkyl groups; R ¹ is selected from C _1-10 alkyl groups.

Further, in the formula, R ¹ is selected from ethyl.

Further, in the formula, at least two of Y ₆ -Y ₈ are hydrogen atoms at the same time; at least two of Y ₁ -Y ₅ are hydrogen atoms at the same time.

The present invention also discloses a synthesis method of the above-mentioned o-hydroxyl-nitrosilane compound, which comprises the following steps: using the salicylidene aniline compound shown in formula II and the alkyl silicon compound shown in formula III as reaction raw materials, in a ruthenium catalyst And under the condition that solvent exists, obtain the o-hydroxy-nitrosilane compound as shown in formula I by heating condition reaction, reaction formula is as follows:

In the formula,

Y ₁ -Y ₉ are independently selected from hydrogen atom, halogen atom, C _1-22 hydrocarbon group, C _1-22 haloalkyl group, hydroxyl group, amino group, carbonyl group, amino group, carboxyl group, ester group, cyano group, phenyl group, benzyl group or nitro;

R ¹ is selected from C _1-22 alkyl groups.

Further, the ruthenium catalyst is selected from triphenylphosphine ruthenium chloride, tris(triphenylphosphine) hydroxy dihydrogen ruthenium, cyclooctadiene ruthenium dichloride or tris(triphenylphosphine) carbonyl hydrochloride A type of ruthenium. The invention adopts a relatively cheap ruthenium complex as a catalyst, which can increase the yield and reduce the cost.

Further, the solvent is selected from one of n-hexane, 1,2-dichloroethane, toluene, N-methylpyrrolidone, N,N-dimethylformamide, tetrahydrofuran or acetonitrile.

Further, the temperature of the heating reaction is 100-120°C.

Further, the heating reaction time is 8-36 hours.

Further, the molar ratio of the salicylidene aniline compound, the alkyl silicon compound and the ruthenium catalyst is 1:1-4:0.01-0.10.

The present invention has the following beneficial effects:

The synthesis method of the present invention is simple to prepare starting materials and easy to operate. Except for the final product, there are no other by-products in a series of conversion processes, no separation and purification are required, only one reaction step is required, and the amount of ruthenium catalyst used is less, and The price is relatively low, which can reduce the investment of capital and labor, greatly improve the synthesis efficiency of this type of skeleton compound, reduce the steps of synthesizing related intermediates, reduce the discharge of by-products such as halogenated hydrocarbons, and provide a A simple and efficient synthetic method.

The o-hydroxy-nitrosilane compound prepared by the invention can be used for special organic synthesis. Silylation in the synthesis of amikacin, penicillin, cephalosporin, fluorouracil and various penicillin derivatives. It can also be used for surface treatment of diatomite, white carbon black, titanium and other powders. Its mechanism of action is condensation of silicon-nitrogen bonds and silicon hydroxyl groups. Used as an adhesion aid for photoresists in the semiconductor industry.

Herein, the term "hydrocarbyl" includes alkyl, alkenyl and alkynyl; "C _1-22 hydrocarbyl" refers to a straight-chain, branched-chain or cyclic alkane group with 1-22 carbon atoms.

"C _1-10 alkyl" refers to an alkyl group with 1 to 10 carbon atoms, including branched, linear or cyclic saturated aliphatic hydrocarbon groups with the specified number of carbon atoms. For example, C _1-10 , as defined in "C _1-10 alkyl" includes 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 in a linear or branched structure group of carbon atoms. For example, "C _1-10 alkyl" specifically includes methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl base and decyl etc.

"C _1-4 alkyl" means an alkyl group with 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl or tert-butyl, etc.

Similarly, "C _1-22 haloalkyl", "C _1-10 haloalkyl" or "C _1-4 haloalkyl" means an alkyl group as defined above substituted by one or more halogen atoms.

The term "halogen" includes F, Cl, Br or I.

Additional aspects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

Description of drawings

Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of 2-((phenyl (triethylsilyl) amino) methyl) phenol in the embodiment 1 of the present invention;

Fig. 2 is the carbon nuclear magnetic resonance spectrogram of 2-((phenyl(triethylsilyl)amino)methyl)phenol in Example 1 of the present invention;

3 is the H NMR spectrum of 2-((((4-fluorophenyl)(triethylsilyl)amino)methyl)phenol in Example 2 of the present invention;

Fig. 4 is the carbon nuclear magnetic resonance spectrogram of 2-((((4-fluorophenyl) (triethylsilyl) amino) methyl) phenol in Example 2 of the present invention;

Fig. 5 is the hydrogen nuclear magnetic resonance spectrogram of 2-((((4-bromophenyl) (triethylsilyl) amino) methyl) phenol in embodiment 3;

Figure 6 is the carbon nuclear magnetic resonance spectrum of 2-((((4-bromophenyl)(triethylsilyl)amino)methyl)phenol in Example 3.

detailed description

In order to describe the technical content, achieved goals and effects of the present invention in detail, the following descriptions will be made in conjunction with the embodiments and accompanying drawings.

Embodiment 1: the preparation of 2-((phenyl (triethylsilyl) amino) methyl) phenol

In a 15mL reaction tube, sequentially add salicylidene aniline (98mg, 0.5mmol), triethylsilane (116mg, 1.0mmol), tris(triphenylphosphine)carbonyl ruthenium hydrochloride (23.8mg, 0.025mmol) , under the conditions of toluene (2 mL) and nitrogen, the reaction temperature was 120 ° C under electromagnetic stirring reaction, and the reaction time was 8 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the mixture was separated by column chromatography. The eluents were ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:10). After separation, a yellow oil body (138 mg, 88%).

The product detection data are as follows:

¹ H NMR (300MHz, CDCl ₃ )δ=7.36-7.16(m,4H),6.97-6.67(m,5H),4.36(s,2H),1.05(t,9H,J=8.1Hz),0.88- 0.80(m,6H).

¹³ C NMR (75 MHz, CDCl ₃ ) δ = 153.9, 148.5, 129.6, 129.3, 129.2, 128.2, 121.3, 118.5, 117.5, 113.1, 43.9, 6.9, 5.5.

Example 2: 2-((((4-fluorophenyl)(triethylsilyl)amino)methyl)phenol

In a 15mL reaction tube, sequentially add 4-fluoro-N-o-hydroxybenzylidene aniline (165mg, 0.5mmol), triethylsilane (116mg, 1.0mmol), tris(triphenylphosphine)carbonyl hydrochloride Ruthenium (23.8 mg, 0.025 mmol) was reacted under toluene (2 mL) and nitrogen under electromagnetic stirring at a reaction temperature of 120° C., and the reaction time was 8 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the mixture was separated by column chromatography. The eluent was ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:10), and a light yellow oil (85mg , 51%).

The product detection data are as follows:

1H NMR (500MHz, CDCl3) δ=7.34-7.32(d, 1H, J=7.5Hz), 7.21-7.17(m, 1H), 7.03-6.99(m, 2H), 6.98-6.94(m, 1H), 6.88-6.76(m,1H),6.74-6.73(m,1H),6.67-6.62(m,1H),4.39(s,2H),1.06-1.03(m,9H),0.85-0.83(m,6H ).

13C NMR (126MHz, CDCl3) δ = 153.7, 152.6 (d, JCF = 239.4Hz), 136.8 (d, JCF = 11.3Hz), 129.0 (d, JCF = 10.1Hz), 128.3, 124.5 (d, JCF = 3.8 Hz), 121.1, 118.2, 116.5(d, JCF=6.3Hz), 114.4(d, JCF=18.9Hz), 112.4(d, JCF=2.5Hz), 43.4, 6.7, 5.3.

Example 3: 2-((((4-bromophenyl)(triethylsilyl)amino)methyl)phenol

In a 15mL reaction tube, sequentially add 4-bromo-N-o-hydroxybenzylidene aniline (137mg, 0.5mmol), triethylsilane (116mg, 1.0mmol), tris(triphenylphosphine)carbonyl hydrochloride Ruthenium (23.8 mg, 0.025 mmol) was reacted under toluene (2 mL) and nitrogen under electromagnetic stirring at a reaction temperature of 120° C., and the reaction time was 8 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the mixture was separated by column chromatography. The eluents were ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:10). After separation, a yellow oil body (170 mg, 87%).

The product detection data are as follows:

¹ H NMR (500MHz, CDC1 ₃ )δ=7.32-7.28(m,3H),7.23-7.21(t,1H,J=7.5Hz),6.98-6.95(t,1H,J=7Hz),6.90-6.89 (d, 1H, J = 8Hz), 6.56-6.55 (t, 2H, J = 4.5Hz), 4.33 (s, 2H), 1.08-1.05 (m, 9H), 0.88-0.83 (m, 6H).

¹³ C NMR (126 MHz, CDC1 ₃ ) δ=153.8, 147.4, 131.9, 129.3, 129.1, 129.0, 128.4, 121.3, 118.4, 114.6, 113.0, 108.9, 43.9, 6.8, 5.4.

In summary, the synthetic method of o-hydroxyl-nitrogen silane compound provided by the present invention has a high yield, and it uses a relatively cheap ruthenium complex as a catalyst, and catalyzes salicylidene aniline compound and The alkyl silicon compound is heated and stirred to synthesize the o-hydroxy-nitrosilane compound; the synthesis method of the invention has good practical value and social and economic efficiency, and has good reference significance for the process development of similar products and downstream products.

The above description is only an embodiment of the present invention, and does not limit the patent scope of the present invention. All equivalent transformations made by using the description of the present invention and the contents of the accompanying drawings, or directly or indirectly used in related technical fields, are all included in the same principle. Within the scope of patent protection of the present invention.

Claims (7)

1. A method for synthesizing an ortho-hydroxy-nitrogen silane compound, wherein the compound has the following general chemical formula:

in the formula (I), the compound is shown in the specification,

Y ₁ -Y ₈ independently selected from C _1-10 Hydrocarbyl radical, C _1-10 A haloalkyl group, a hydrogen atom or a halogen atom;

R ¹ is selected from C _1-10 An alkyl group;

the synthesis method of the ortho-hydroxyl-nitrogen silane compound comprises the following steps: taking a salicylidene aniline compound shown as a formula II and an alkyl silicon compound shown as a formula III as reaction raw materials, and reacting under a heating condition in the presence of a ruthenium catalyst and a solvent to obtain an o-hydroxy-nitrogen silane compound shown as a formula I, wherein the reaction formula is as follows:

in the formula (I), the compound is shown in the specification,

the ruthenium catalyst is selected from one of triphenylphosphine ruthenium chloride, tri (triphenylphosphine) hydroxyl ruthenium dihydrogen, cyclooctadiene ruthenium dichloride or tri (triphenylphosphine) carbonyl ruthenium hydrochloride.

2. The method of claim 1, wherein R is ¹ Selected from ethyl.

3. The synthesis process according to claim 1, wherein, in the formula,

Y ₆ -Y ₈ in (b), at least two of them are hydrogen atoms at the same time;

Y ₁ -Y ₅ at least 2 of which are simultaneously hydrogen atoms.

4. The method of claim 1, wherein the solvent is selected from the group consisting of N-hexane, 1, 2-dichloroethane, toluene, N-methylpyrrolidone, N-dimethylformamide, tetrahydrofuran, and acetonitrile.

5. The synthesis method according to claim 1, wherein the temperature of the heating reaction is 100-120 ℃.

6. The synthesis method according to claim 1, wherein the heating reaction time is 8-36 hours.

7. The synthesis method according to claim 1, wherein the molar weight ratio of the substances of the salicylideneaniline compound, the alkyl silicon compound and the ruthenium catalyst is 1:1-4:0.01-0.10.

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