阅读说明：本技术 一种烯烃高效双官能团化制备2-碘-1-磷酰基取代烷烃化合物的方法 (Method for preparing 2-iodo-1-phosphoryl substituted alkane compound by high-efficiency double functionalization of olefin ) 是由 熊碧权 王刚 祝雨 刘宇 许卫凤 唐课文 于 2019-09-23 设计创作，主要内容包括：本发明提供了一种高效、高选择性合成含不同官能团取代的2-碘-1-磷酰基取代烷烃化合物的方法,其采用<I>N</I>-碘代丁二酰亚胺(NIS)作为促进剂,以含P(O)-OH类化合物与烯烃作为反应底物,反应体系加入了有机溶剂。该方法的优点：促进剂廉价易得；底物适用性高；反应条件温和,安全可靠；所得目标产物的选择性接近100%,产率高达90%以上。该方法开发了一条合成含不同官能团的取代2-碘-1-磷酰基取代烷烃化合物的新途径,解决了传统合成2-碘-1-磷酰基取代烷烃化合物的反应选择性差、反应步骤繁琐、产率低以及需要用到对环境有害试剂等不足,具有良好的工业应用前景。本发明同时还提供了对应的含不同官能团取代的2-碘-1-磷酰基取代烷烃类衍生物。(The invention provides a method for efficiently and selectively synthesizing 2-iodo-1-phosphoryl substituted alkane compounds containing different functional groups, which adopts N Iodosuccinimide (NIS) is used as an accelerator, a compound containing P (O) -OH and olefin are used as reaction substrates, and an organic solvent is added into a reaction system. The method has the advantages that: the accelerant is cheap and easy to obtain; the substrate applicability is high; the reaction condition is mild, safe and reliable; the selectivity of the obtained target product is close to 100 percent, and the yield is up to more than 90 percent. The method develops a new way for synthesizing the substituted 2-iodo-1-phosphoryl substituted alkane compound containing different functional groups, and solves the problems of poor reaction selectivity, complicated reaction steps, low yield and the need of using para-rings in the traditional method for synthesizing the 2-iodo-1-phosphoryl substituted alkane compoundEnvironmental harmful reagents and the like, and has good industrial application prospect. The invention also provides corresponding 2-iodine-1-phosphoryl substituted alkane derivatives containing different functional groups.)

1. The P (O) -OH compound and olefin are efficiently bifunctional to prepare the compound with the structural formula（I）The preparation method of the 2-iodo-1-phosphoryl substituted alkane compound comprises the following steps:

（I）

the method is characterized by comprising the following steps:

taking reaction amount of P (O) -OH compound, olefin, iodinating agent and organic solvent in N₂Mixing in a reaction vessel under protection, stirring at 25 ~ 80^oReacting for 3 ~ 12 hours under C to obtain corresponding 2-iodo-1-phosphoryl substituted alkane compounds containing different functional groups;

wherein the content of the first and second substances,

R¹is selected from phenyl, 4-methylphenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-fluorophenyl, benzyl, acetoxy, undecanoyl, 4-methoxyphenyl;

R²is hydrogen, methyl;

R³is phenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl, 3-fluorophenyl, ethoxy, butoxy, benzyloxy, phenoxy.

R⁴Is phenyl, methyl, 4-methylphenyl, 3, 5-dimethylphenyl, 4-methylOxyphenyl, 1-naphthyl, 2-naphthyl, 3-fluorophenyl, ethoxy, butoxy, benzyloxy, phenoxy.

2. The method according to claim 1, wherein the P- (O) -OH-containing compound is selected from diphenyl phosphate, bis (4-methyl-phenyl) phosphate, bis (3, 5-dimethyl-phenyl) phosphate, bis (4-methoxy-phenyl) phosphate, bis (1-naphthyl) phosphate, bis (2-naphthyl) phosphate, bis (3-fluoro-phenyl) phosphate, phenylmethyl phosphate, diethoxy phosphate, dibutoxy phosphate, dibenzyloxy phosphate, and diphenoxy phosphate.

3. The method of claim 1, wherein the olefin is selected from the group consisting of styrene, 4-methylstyrene, 4-bromostyrene, 3-bromostyrene, 2-bromostyrene, 4-fluorostyrene, allylbenzene, vinyl acetate, vinyl undecanoate, 4-methoxystyrene, and 1-propenylbenzene.

4. The method according to claim 1, wherein the organic solvent is dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, toluene, or a mixture thereof,N, N-dimethylformamide, dimethyl sulfoxide, methanol, ethanol, 1, 4-dioxane, ethyl acetate.

5. The method of claim 1, wherein the iodinating agent is selected from the group consisting ofN-iodosuccinimide.

6. The method according to claim 1, wherein the molar ratio of the P (O) -OH compound to the olefin is 1: [1.0 ~ 2.0.0 ].

7. The method according to claim 1, wherein the molar ratio of the P- (O) -OH-containing compound to the iodinating agent is 1: [1.0 ~ 1.5.5 ].

Technical Field

The invention relates to the field of application catalytic synthesis of organic phosphate compounds, in particular to a method for preparing 2-iodo-1-phosphoryl substituted alkane compounds by using a P (O) -OH compound and olefin to perform high-efficiency bifunctional reaction.

Background

The organic phosphate ester compound is an important organic compound in organic synthesis, and the compound has good catalytic activity, optical activity and biological activity, so that the compound has wide application in the aspects of biological, medical and optical active materials, asymmetric catalytic synthesis and the like. Phosphorus and organic phosphorus compounds are known to be important substrates in life, such as ADP, ATP, RNA, organic phospholipid bilayers and the like in human bodies. However, it is difficult to find out a natural organic phosphate compound in nature, and most of phosphorus exists in nature in the form of inorganic salt, and most of organic phosphate compounds known at present are synthesized by a chemical method.

In recent years, with the continuous expansion of the application field of organic phosphate (especially as organic ligand), the market demand is also increasing, and the development of new synthesis technology of the compounds is also receiving more and more attention. The synthesis method of the 2-iodo-1-phosphoryl substituted alkane compound reported in the literature at present mainly comprises the following steps: (1) Atherton-Todd reaction: catalyzing a compound containing a corresponding P (O) -H bond to perform cross coupling reaction with alpha-iodophenethyl alcohol in the presence of reagents such as carbon tetrachloride, triethylamine and the like; (2) nucleophilic substitution reaction: the compound containing P (O) -H or P (O) -OH reacts with a halogenating agent to prepare a corresponding compound containing P (O) -Cl, and then the compound and alpha-iodophenethyl alcohol are subjected to cross coupling reaction; (3) ester exchange reaction: the catalyst is prepared by the ester exchange reaction of alpha-iodophenethyl alcohol and diaryl methyl phosphonate. However, the above methods generally employ air-sensitive reagents (p (o) -H compounds, carbon tetrachloride, sulfonyl chloride, etc.), and have the disadvantages of complicated experimental steps, expensive catalyst, difficult recycling, harsh reaction conditions, cross-reactivity of substrates, low yield, and great environmental pollution.

So far, the high-efficiency synthesis of 2-iodine-1-phosphoryl substituted alkane compounds still has the problems of raw material quality, production safety (the compounds such as phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride and the like have strong corrosiveness) and stability, purity and the like of products, the synthesis technology has great difficulty, only a plurality of companies in countries such as the United states and the Japan are used for production at present, and the current situation of high-end organic phosphate products in China mainly depends on import.

Aiming at the defects of the existing synthesis process of 2-iodo-1-phosphoryl substituted alkane compounds, the industry is developing a method for efficiently and selectively synthesizing corresponding organic phosphate compounds by using stable, cheap and easily obtained P (O) -OH-containing compounds as raw materials.

Disclosure of Invention

The object of the present invention is to provide a method for producing a polymer with low cost and easy availabilityNThe method for synthesizing the corresponding 2-iodo-1-phosphoryl substituted alkane compound containing different substituted functional groups by promoting the double functionalization reaction of the P (O) -OH compound and the alkene compound with high efficiency and high selectivity by using the iodo-succinimide so as to overcome the defects in the prior art.

The invention provides a novel compound which is cheap and easily availableNThe method for synthesizing the corresponding 2-iodo-1-phosphoryl substituted alkane compound containing different functional group substitutions by promoting the P (O) -OH compound and the alkene compound to perform the bifunctional reaction with high efficiency and high selectivity by using the iodosuccinimide comprises the following steps: taking reaction amount of P (O) -OH compound, olefin, iodinating agent and organic solvent in N₂Mixing in a reaction vessel under protection, stirring at 25 ~ 80^oReacting for 3 ~ 12 hours under the condition of C to obtain the corresponding 2-iodo-1-phosphoryl substituted alkane compound containing different functional groups, wherein the specific reaction formula is as follows:

wherein the content of the first and second substances,

R¹is selected from phenyl, 4-methylphenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-fluorophenyl, benzyl, acetoxy, undecanoyl, 4-methoxyphenyl;

R²is hydrogen, methyl;

R³is phenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl, 3-fluorophenyl, ethoxy, butoxy, benzyloxy, phenoxy;

R⁴is phenyl, methyl, 4-methylphenyl, 3, 5-dimethylphenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl, 3-fluorophenyl, ethoxy, butoxy, benzyloxy, phenoxy.

In the above method for efficiently bifunctional synthesis of a 2-iodo-1-phosphoryl-substituted alkane compound from a p (o) -OH compound and an olefin, the p (o) -OH compound in the reaction step is selected from diphenyl phosphate, bis (4-methyl-phenyl) phosphate, bis (3, 5-dimethyl-phenyl) phosphate, bis (4-methoxy-phenyl) phosphate, bis (1-naphthyl) phosphate, bis (2-naphthyl) phosphate, bis (3-fluoro-phenyl) phosphate, phenylmethyl phosphate, diethoxy phosphate, dibutoxy phosphate, dibenzyloxy phosphate, and diphenoxy phosphate.

In the method for efficiently bifunctional synthesis of 2-iodo-1-phosphoryl substituted alkane compound from P (O) -OH compound and olefin, the olefin compound in the reaction step is selected from styrene, 4-methylstyrene, 4-bromostyrene, 3-bromostyrene, 2-bromostyrene, 4-fluorostyrene, allyl benzene, vinyl acetate, vinyl undecanoate, 4-methoxystyrene, and 1-propenylbenzene.

In the method for synthesizing the 2-iodo-1-phosphoryl substituted alkane compound by efficiently bifunctional synthesis of the P (O) -OH compound and the olefin, the organic solvent refers to dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, toluene, or mixtures thereof,N, N-dimethylformamide, dimethyl sulfoxide, methanol, ethanol, 1, 4-dioxane, ethyl acetate.

In the method for synthesizing the 2-iodo-1-phosphoryl substituted alkane compound by efficiently bifunctional synthesis of the P (O) -OH compound and the olefin, the iodinating reagent refers toN-iodosuccinimide.

In the method for synthesizing the 2-iodo-1-phosphoryl substituted alkane compound by efficiently bifunctional synthesis of the P (O) -OH compound and the olefin, the molar ratio of the P (O) -OH compound to the olefin is 1: [1.0 ~ 2.0.0 ], and the molar ratio of the P (O) -OH compound to the iodinating agent is 1: [1.0 ~ 1.5.5 ].

The invention provides a method for synthesizing 2-iodo-1-phosphoryl substituted alkane compounds by promoting a bifunctional reaction of a P (O) -OH compound and an alkene compound to efficiently and selectively react by using an iodinating reagent, and the reaction process is mild and easy to control. The method is simple and easy to implement while obtaining higher yield and 100 percent selectivity, and the used accelerant is cheap and easy to obtain, the preparation is simple, and the method has good industrial application prospect.

[ detailed description ] embodiments

The invention is further illustrated below with reference to examples of the invention:

first, testing and analyzing

The structural analysis of the reaction products in the following examples of the present invention employed GC/MS (6890N/5973N) gas-mass spectrometer equipped with HP-5MS capillary chromatography column (30 m.times.0.45 mm.times.0.8 μm) manufactured by Agilent and Bruker Avance-III 500 NMR analyzer manufactured by Bruker. The selectivity and yield of the target product were analyzed by Agilent GC 7820A, a gas chromatograph equipped with a hydrogen flame detector, AB-FFAP capillary chromatography column (30 m. times.0.25 mm. times.0.25 μm), manufactured by Agilent.