CN106674277A - Preparation method of olefin phosphate compound - Google Patents

Abstract

The invention discloses a preparation method of an olefin phosphate compound. The method comprises the following steps: arylethylene and phosphate according to a mol ratio 1:4-6 are used as raw materials; ferric chloride and copper salt are used as catalysts, and di-tert-butyl peroxide is used as an oxidizing agent; the raw materials and triethylamine are mixed, an organic solvent is added, and under the protection of inert gas, a reaction is carried out at 90-110 DEG C; after the reaction ends, washing is carried out, rotary evaporation is used for removing the solvent, and column chromatography is carried out in order to obtain the olefin phosphate compound. Base metal copper and iron are used as catalysts, reactant arylethylene and phosphate have low price, toxicity is low, the oxidizing agent is green and environmentally friendly, and the yield of the synthetic reaction of the olefin phosphate compound is high.

Description

A kind of preparation method of enophosphate compound

technical field

The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of enophosphate compounds.

Background technique

Elenyl phosphate compounds are a class of organic synthesis intermediates that are widely used, and can be used to synthesize bioactive molecules, flame retardants, and polymer additives. Enenophosphate compounds are also widely used in Michael addition and Horner-Wadsworth-Emmons (HWE) reactions to realize the synthesis of compounds. At the same time, the enphosphonate compound can also be used as the precursor of L-AP4, an effective drug for treating central nervous diseases such as Parkinson's disease and Alzheimer's disease. Therefore, it is of great importance to develop efficient organic synthesis methods for the synthesis of enophosphate compounds.

At present, the main synthesis methods of enophosphonates are the addition phosphorylation of alkynes and the phosphorylation of functionalized alkenes. Although transition metal-catalyzed coupling reactions of haloalkynes and phosphate esters can efficiently synthesize enophosphonate compounds, equivalent by-products will be formed. Therefore, the direct addition reaction of alkynes and phosphates has been widely used in the synthesis of enophosphates due to its 100% atom economy. Transition metals Pd, Pt, Rh, etc. can effectively realize the hydrogen phosphorylation of terminal alkynes, thereby realizing the synthesis of enphosphoesters. However, this method often has some disadvantages, such as the stereoselectivity of the reaction process is not easy to control, A mixture of Z/E configuration products will be generated, or the reaction requires noble metals for catalysis ([1] Liu, L.; et al. Experimental and Theoretical Studies on Nickel–Zinc-Catalyzed Cross-Coupling of Gem-Dibromoalkenes with P (O)–H Compounds[J].RSC Advances.2014,4:2322-2326.[2]Han,L.; et al.Palladium-Catalyzed Dehydrogenative Cis Double Phosphorylation ofAlkynes with H-Phosphonate Leading to(Z)- Bisphosphoryl-1-alkenes. J. Am. Chem. Soc [J]. 2008:130, 2752-2753.). Phosphorylation of substituted alkenes is also an effective method for the synthesis of enophosphonate compounds, but the reaction produces equivalent by-products, so the atom economy is not high. Therefore, how to use cheap catalysts to efficiently prepare enphosphonate compounds with specific stereoselectivity has a good application prospect.

Contents of the invention

The object of the present invention is to provide a kind of preparation method of enphosphoester compound.

The technical scheme that realizes the object of the present invention is as follows:

A kind of preparation method of enophosphate compound, concrete reaction formula is as follows:

Specific steps are as follows:

Using aryl vinyl and phosphoric acid ester with a molar ratio of 1:4~6 as raw materials, ferric chloride and copper salt as catalyst, di-tert-butyl peroxide as oxidant, after mixing with triethylamine, adding organic solvent, Under the protection of an inert gas, react at 90-110°C. After the reaction, wash with water, remove the solvent by rotary evaporation, and obtain enphosphoester compounds through column chromatography.

The aryl vinyl is selected from styrene, 4-methylstyrene, 2,4,6-trimethylstyrene, 4-methoxystyrene, 4-tert-butylstyrene, 4-acetoxy One of phenylstyrene, 4-fluorostyrene, 4-chlorostyrene, 4-bromostyrene, α-methylstyrene, 2-vinylpyridine and 2-vinylthiophene.

The phosphoric acid ester is selected from one of diisopropyl phosphite, dibutyl phosphite and dimethyl phosphite.

The copper salt is selected from cuprous chloride, copper trifluoromethanesulfonate or cuprous oxide.

The organic solvent is dimethylsulfoxide or N,N'-dimethylformamide.

Compared with prior art, advantage of the present invention is as follows:

Using low-cost, low-toxic arylene and phosphate as raw materials, using non-precious metal copper and iron as catalysts, avoiding the use of precious metals, the oxidant di-tert-butyl peroxide is green and environmentally friendly, and the reaction yield is high. Efficient synthesis of enophosphonate compounds.

detailed description

Example 1

Take 0.05mmol of cuprous chloride and 0.1mmol of ferric chloride, add them into the reaction tube, replace the air in the reaction tube with argon, add 0.5mmol of styrene, 2.0mmol of diethyl phosphite, and 1.0mmol of di-tert-butyl base peroxide, 0.5mmol triethylamine, 2mL dimethyl sulfoxide solvent, in an oil bath at 110°C, stop the reaction after 16 hours of reaction, filter, wash with water, remove the organic solvent by rotary evaporation, and obtain pure The yield of enophosphate is 78%.

Example 2

Take 0.05mmol cuprous chloride, 0.1mmol ferric chloride, add to the reaction tube, replace the air in the reaction tube with argon, add 0.5mmol p-methylstyrene, 2.0mmol diethyl phosphite, 1.0mmol Di-tert-butyl peroxide, 0.5mmol triethylamine, 2mL dimethyl sulfoxide solvent, in an oil bath at 110°C, stop the reaction after 16 hours of reaction, filter, wash with water, remove the organic solvent by rotary evaporation, and pass through column chromatography on silica gel , to obtain the pure target product, the yields were 82%.

Example 3

The procedure of this example is the same as that of Example 2, the only difference is that styrene is replaced by 2,4,6-trimethylstyrene, and the yield is 63%.

Example 4

The procedure of this example is the same as Example 2, the only difference is that styrene is replaced by 4-methoxystyrene, and the yield is 76%.

Example 5

The procedure of this example is the same as Example 2, the only difference is that styrene is replaced by 4-tert-butylstyrene, and the yield is 81%.

Example 6

The procedure of this example is the same as that of Example 2, the only difference is that styrene is replaced by 4-acetoxystyrene, and the yield is 75%.

Example 7

The procedure of this example is the same as Example 2, the only difference is that styrene is replaced by 4-fluorostyrene, and the yield is 72%.

Example 8

The procedure of this example is the same as Example 2, the only difference is that styrene is replaced by 4-chlorostyrene, and the yield is 69%.

Example 9

The procedure of this example is the same as Example 2, the only difference is that styrene is replaced by 4-bromostyrene, and the yield is 71%.

Example 10

The procedure of this example is the same as Example 2, the only difference is that styrene is replaced by α-methylstyrene, and the yield is 65%.

Example 11

Take 0.05mmol cuprous chloride, 0.1mmol ferric chloride, add to the reaction tube, replace the air in the reaction tube with argon, add 0.5mmol 2-vinylpyridine, 2.0mmol diethyl phosphite, 1.0mmol Tert-butyl peroxide, 0.5mmol triethylamine, 2mL dimethyl sulfoxide solvent, in an oil bath at 110°C, stop the reaction after 16h, filter, wash with water, remove the organic solvent by rotary evaporation, and pass through column chromatography on silica gel, The pure target products were obtained with yields of 45%.

Example 12

The procedure of this example is the same as that of Example 11, the only difference is that 2-vinylpyridine is replaced by 2-vinylthiophene, and the yield is 78%.

Example 13

Take 0.05mmol of cuprous chloride and 0.1mmol of ferric chloride, add them into the reaction tube, replace the air in the reaction tube with argon, add 0.5mmol of styrene, 2.0mmol of diisopropyl phosphite, and 1.0mmol of tert-butyl base peroxide, 0.5mmol triethylamine, 2mL dimethyl sulfoxide solvent, in an oil bath at 110°C, stop the reaction after 16 hours of reaction, filter, wash with water, remove the organic solvent by rotary evaporation, and obtain pure The yields of the target products were 73%.

Example 14

The procedure of this example is the same as Example 13, the only difference is that diisopropyl phosphite is replaced by dibutyl phosphite, and the yield is 56%.

Example 15

The procedure of this example is the same as that of Example 13, the only difference is that diisopropyl phosphite is replaced by dimethyl phosphite, and the yield is 62%.

Example 16

Reaction steps are identical with embodiment 1, difference is:

The copper salt is copper trifluoromethanesulfonate, and the yield of enophosphate is 45%.

Example 17

Reaction steps are identical with embodiment 1, difference is:

The copper salt is cuprous oxide, and the yield of enophosphate is 33%.

Example 18

The procedure of this example is the same as that of Example 1, the only difference is that the reaction solvent is N,N'-dimethylformamide, and the yield of enophosphate is 68%.

Example 19

The procedure of this example is the same as that of Example 1, the only difference is that the reaction temperature is 100° C., and the yield of enphosphoester is 30%.

Example 20

The procedure of this example is the same as that of Example 1, the only difference is that the reaction temperature is 90° C., and the yield of enphosphoester is 25%.

Example 21

The procedure of this example is the same as that of Example 1, the only difference is that the material ratio of styrene and diethyl phosphite is 1:5, and the yield of enphosphoester is 75%.

Example 22

The procedure of this example is the same as that of Example 1, the only difference is that the material ratio of styrene and diethyl phosphite is 1:6, and the yield of enphosphoester is 77%.

Claims (5)

1. a kind of preparation method of alkenyl phosphoric acid ester type compound, it is characterised in that comprise the following steps that：With mol ratio as 1:4~6 Aryl ethylene and phosphate ester be raw material, ferric chloride and mantoquita are catalyst, and di-tert-butyl peroxide is oxidant, with three After ethamine mixing, organic solvent is added, under inert gas shielding, reacted at 90~110 DEG C, after reaction terminates, washing, revolving Solvent is removed, Jing column chromatographies obtain alkenyl phosphoric acid ester type compound.

2. preparation method according to claim 1, it is characterised in that described aryl ethylene is selected from styrene, 4- methyl Styrene, 2,4,6- trimethyl styrenes, 4- methoxy styrenes, 4- t-butyl styrenes, 4- acetoxy-styrenes, 4- fluorine Styrene, 4- chlorostyrenes, 4- bromstyrols, α-methyl styrene, the one kind in 2- vinylpyridines and 2- vinyl thiophenes.

3. preparation method according to claim 1, it is characterised in that described phosphate ester is selected from diisopropyl phosphite, One kind in dibutyl phosphite and dimethylphosphite.

4. preparation method according to claim 1, it is characterised in that described mantoquita is selected from Cu-lyt., fluoroform Sulfonic acid copper or Red copper oxide.

5. preparation method according to claim 1, it is characterised in that described organic solvent is dimethyl sulfoxide or N, N '- Dimethylformamide.