Method for synthesis of 5-nitryl-4, 5-dihydrofuran derivant

Technical Field

The invention relates to the field of organic synthesis, particularly relates to a synthetic 5-nitro -4, 5-dihydrofuran derivative.

Background Art

In the organic chemistry is a dihydrofuran derivative intermediates for the synthesis of such very important, the furan derivatives can be synthesized by oxidation, can also be through reduction to obtain tetrahydrofuran derivatives, further used in pharmaceutical and important in the synthesis of natural product.

In the prior art, 5-nitro -4, 5-dihydrofuran derivative preparation only 1 related reports:

(1) the E.V.Trukhin through the acetyl acetone and β, β-dnb ethylene in the presence of sodium methoxide Michael addition reaction occurs, the reaction-3--5 the first under [...] 1 hour, then heating to 18-20 the reaction under [...] 2 hours, to obtain an intermediate product, the yield is 70%;

Then using triethylamine as catalyst, water-free methanol as a solvent, catalytic intermediates to produce 5-nitro -4, 5-dihydro-furan derivatives, in the temperature control of reaction the 18-20 [...] , the reaction time is 2 days, the step yield is 80% ; total yield of about 56%.

The reaction process is as follows:

Visible, special requirements of the reaction to the substrate (β, β-dnb ethylene), two-step reaction needs to be completed, the by-product of the reaction generated in harmful to the environment nitrite (Russian   Journal   of   Organic Chemistry, 2004, 40, 1823-1825).

In the above-mentioned method, the reaction is more complex, more harsh reaction conditions, the yield is low; reactant to the special structure, type side, does not have many synthesized product, the defects of the prior art, therefore the development of green high-efficient synthetic method is very important.

Content of the invention

The purpose of this invention is to provide a kind of synthetic 5-nitro -4, 5-dihydrofuran derivative method, in order to improve the productive rate, optimizing preparation process, simplify the reaction process and operation, shorten the reaction time, and can be applied to the reaction substrate is relatively wide.

In order to achieve the above object, the technical proposal of the invention is:a kind of synthetic 5-nitro -4, 5-dihydrofuran derivative method, in order to And acetylacetone manganese (III) as the reactant, with ethanol as the solvent, for 30-70 the reaction under [...] 1-4 hours, preparation 5-nitro -4, 5-dihydro-furan derivatives;

The In the substituent R is selected from the group with aromatic penta-ring or six-membered ring, Is selected from:

Β-nitrostyrolene or its derivatives

Β-nitro pyridine ethylene or its derivatives

Β-nitrofuran ethylene or its derivatives

Β-nitro thiophene ethylene or its derivatives

Β-nitro pyrrole ethylene or its derivatives

Or β-nitro-N-methyl pyrrole ethylene or its derivatives A in;

Said β-nitrostyrolene or its derivatives, β-nitro pyridine ethylene or its derivatives, β-nitrofuran ethylene or its derivatives, β-nitro thiophene ethylene or its derivatives, β-nitro pyrrole ethylene or its derivatives, or β-nitro-N-methyl pyrrole ethylene or its derivatives are electron deficient compound;

In the above-mentioned technological scheme, R¹, R², R³ the selection of one of the following scheme:

(1) when the R¹ is selected from the group consisting of: hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, positive butoxypolyethylene, isobuoxy, tert-butoxy, fluoro, chloro, bromo, iodo, nitro or phenyl in a time of, R² = R³ =H;

(2) when the R² selected from: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, positive butoxypolyethylene, isobuoxy, tert-butoxy, fluoro, chloro, bromo, iodo; nitro, phenyl, carboxyl or benzoyl in a time of, R¹ = R³ =H;

(3) when the R³ selected from: methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, positive butoxypolyethylene, isobuoxy, tert-butoxy, fluoro, chloro, bromo, iodo, nitro or phenyl in a time of, R¹ = R² =H;

(4) when the R² = a basetime, R¹ =H, R³ is selected from methyl, ethyl, methoxy or ethoxy, a;

(5) when the R² = a basetime, R¹ is selected from methyl, ethyl, methoxy, ethoxy, fluorine, chlorine, bromine or iodine in a; R³ =H;

(6) when the R¹ = nitrio, R² = H time, R³ is selected from methyl, ethyl, methoxy, ethoxy, fluorine, chlorine, bromine or iodine in a;

(7) when the R² = nitrio, R¹ = H time, R³ is selected from methyl, ethyl, methoxy, ethoxy, fluorine, chlorine, bromine or iodine in a;

(8) when the R³ = nitrio, R¹ = H time, R² is selected from methyl, ethyl, methoxy, ethoxy, fluorine, chlorine, bromine or iodine in a;

In the above-mentioned technological scheme, the reaction process can be expressed as:

Further technical scheme, when the reactant Is selected from β-nitrostyrolene or its derivatives, the reaction process can be expressed as:

Said β-nitrostyrolene or its derivative is selected from the group consisting of: ethylene-nitrophenyl β, 4-methyl-β-nitrostyrolene, 4-methoxy-β-nitrostyrolene, 4-chloro-β-nitrostyrolene, 4-nitro-β-nitrostyrolene, 4-fluoro-β-nitrostyrolene 4-bromo-β-nitrostyrolene, 2-fluoro-β-nitrostyrolene or 3-nitro-β-nitrostyrolene a; said β-nitrobenzene ethylene and its derivative and acetylacetone manganese (III) molar ratio is greater than 1 the [...] 3, the preferred technological scheme, β-nitrobenzene ethylene and its derivative and acetylacetone manganese (III) is equal to the molar ratio of the 1 [...] 3.

When the reactant is β-nitrofuran ethylene or its derivatives, β-nitro thiophene ethylene or its derivatives, β-nitro pyrrole ethylene or its derivative in a time of, the reaction process is expressed as:

In the above-mentioned technological scheme, β-nitrofuran ethylene or its derivatives selected from (X=O): β-nitrofuran ethylene, 3-methyl-β-nitrofuran ethylene, 3-fluoro-β-nitrofuran ethylene, 3-nitro-β-nitrofuran ethylene, 4-methoxy-β-nitrofuran ethylene, 4-chloro-β-nitrofuran ethylene, 4-nitro-β-nitrofuran ethylene, 5-fluoro-β-nitrofuran ethylene or 5-bromo-β-nitrofuran ethylene in a;

Β-nitro thiophene ethylene or its derivatives selected from (X=S): β-nitro thiophene ethylene, 3-methyl-β-nitro thiophene ethylene, 3-fluoro-β-nitro thiophene ethylene, 3-nitro-β-nitro thiophene ethylene, 4-methoxy-β-nitro thiophene ethylene, 4-chloro-β-nitro thiophene ethylene, 4-nitro-β-nitro thiophene ethylene, 5-fluoro-β-nitro thiophene ethylene or 5-bromo-β-nitro thiophene ethylene in a;

Β-nitro pyrrole ethylene or its derivatives selected from (X=NH): β-nitro pyrrole ethylene, 3-methyl-β-nitro pyrrole ethylene, 3-fluoro-β-nitro pyrrole ethylene, 3-nitro-β-nitro pyrrole ethylene, 4-methoxy-β-nitro pyrrole ethylene, 4-chloro-β-nitro pyrrole ethylene, 4-nitro-β-nitro pyrrole ethylene, 5-fluoro-β-nitro pyrrole ethylene or 5-bromo-β-nitro pyrrole ethylene in a;

Β-nitro pyrrole ethylene or its derivatives (X=NCH₃) selected from: β-nitro pyrrole ethylene, 3-methyl-β-nitro pyrrole ethylene, 3-fluoro-β-nitro pyrrole ethylene, 3-nitro-β-nitro pyrrole ethylene, 4-methoxy-β-nitro pyrrole ethylene, 4-chloro-β-nitro pyrrole ethylene, 4-nitro-β-nitro pyrrole ethylene, 5-fluoro-β-nitro pyrrole ethylene or 5-bromo-β-nitro pyrrole ethylene in a; said β-nitrofuran ethylene or its derivatives, β-nitro thiophene ethylene or its derivatives, β-nitro pyrrole ethylene or derivatives thereof with acetylacetone manganese (III) molar ratio is greater than 1 the [...] 3, preferred technique in the programme, β-nitrobenzene ethylene and its derivative and acetylacetone manganese (III) is equal to the molar ratio of the 1 [...] 3.

When the reactant is selected from β-nitro pyridine ethylene or its derivatives, the reaction process is expressed as:

In the above-mentioned technological scheme, β-nitro pyridine ethylene or its derivative is selected from the group consisting of: ethylene β-nitro pyridine, 4-methyl-β-nitro pyridine ethylene, 4-fluoro-β-nitro pyridine ethylene, 4-nitro-β-nitro pyridine ethylene, 5-methoxy-β-nitro pyridine ethylene, 5-chloro-β-nitro pyridine ethylene, 5-nitro-β-nitro pyridine ethylene, 6-fluoro-β-nitro pyridine ethylene, 6-bromo-β-nitro pyridine ethylene or 6-chloro-β-nitro pyridine ethylene in a; said β-nitro pyridine ethylene and its derivative and acetylacetone manganese (III) molar ratio is greater than 1 the [...] 3, preferred technique in the programme, β-nitro pyridine ethylene and its derivative and acetylacetone manganese (III) is equal to the molar ratio of the 1 [...] 3.

The use of the because of the above-mentioned technical scheme, compared with the prior art, the present invention has the following advantages:

1. The invention uses various electron deficient the nitryl alkene as reaction raw material, there are many kinds of such compounds, it is simple to synthesize; a large number of the product types, can be conveniently further reaction, to obtain the required compound with a certain function.

2. The method utilizes a green solvent ethanol, avoid the use of other toxic organic solvent, not only reducing the pollution, to simplify the reaction operation and the post-processing process, also can shorten the reaction time, and cheap solvent is ethanol, is easy to obtain, thus reducing the production cost.

3. The method is used to synthesize 5-nitro -4, 5-dihydro-furan derivatives, because of the ethylene-nitro-β on the role of the double bond, the reactant electron deficient, easily and nucleophilic reagent reaction, but also has the advantages of good selectivity, the advantage of high yield, synthetic product can be regarded as potential having physiological activity of the molecule and important key intermediate.