阅读说明：本技术 一种硝基烯烃的还原方法 (A kind of restoring method of nitroolefin ) 是由 熊凯 魏文国 于 2019-09-16 设计创作，主要内容包括：本发明涉及有机合成技术领域,具体公开了一种硝基烯烃的还原方法。将化合物1加入到一定比例的醇/水的混合溶剂中,在0-50℃下,加入金属硼氢化物,搅拌反应；将所得溶液浓缩至恒重,向浓缩物中加入乙酸乙酯和饱和氯化铵溶液；分液得上层乙酸乙酯层,干燥,浓缩得还原产物化合物2。本发明的合成方法对芳环及直链烷烃均适用,本发明可以控制二聚体杂质在3.0%以下,脂肪族或芳香族硝基化合物HPLC纯度在95.0%以上。本发明的合成方法原料价格便宜,工艺绿色环保,经济实用,适于工业化生产。(The present invention relates to technical field of organic synthesis, specifically disclose a kind of restoring method of nitroolefin.Compound 1 is added to the in the mixed solvent of a certain proportion of alcohol/water, at 0-50 DEG C, metallic boron hydrides is added, is stirred to react；Acquired solution is concentrated into constant weight, ethyl acetate and saturated ammonium chloride solution are added into concentrate；Liquid separation obtains upper layer ethyl acetate layer, dry, is concentrated to give reduzate compound 2.Synthetic method of the invention is applicable in aromatic ring and linear paraffin, and the present invention can control dimer impurity 3.0% hereinafter, aliphatic or aromatic nitro compound HPLC purity are 95.0% or more.Synthetic method cost of material of the invention is cheap, and technique is environmentally protective, economical and practical, is suitable for industrialized production.)

1. a kind of restoring method of nitroolefin, includes the following steps:

Step (1): being added to alcohol/water in the mixed solvent for compound 1, and at 0-50 DEG C, reducing agent metal hydroboration is added Object is stirred to react；

Step (2): being concentrated into constant weight for step (1) resulting solution, and ethyl acetate and saturated ammonium chloride are added into concentrate Solution；

Step (3): liquid separation obtains upper layer ethyl acetate layer, dry, is concentrated into constant weight and obtains reduzate compound 2；

Wherein, the R in compound 1 and compound 2₁Any one in C1-C8 straight chained alkyl and general formula functional group 1, R₂For Hydrogen or methyl, R₃、R₄、R₅、R₆、R₇It is each independently selected from one of hydrogen, methyl, methoxyl group or hydroxyl；

Mixed solvent dosage and the ratio of compound 1 are (5-30) mL:1g；

Alcohol in the step (1) is one of methanol, ethyl alcohol, normal propyl alcohol and isopropanol；

Metallic boron hydrides in the step (1) is one in lithium borohydride, sodium borohydride, potassium borohydride and zinc borohydride Kind.

2. restoring method according to claim 1, which is characterized in that the volume ratio of the in the mixed solvent alcohol and water is (2-10): 1.

3. restoring method according to claim 1 or 2, which is characterized in that metallic boron hydrides and compound in step (1) 1 molar ratio is (0.5-3): 1.

4. restoring method according to claim 3, which is characterized in that extractant ethyl acetate described in step (2) is satisfied Amount ratio with compound 1 described in the dosage of ammonium chloride solution and step (1) is (2-10) mL:(2-10) mL:1g.

5. restoring method according to claim 4, which is characterized in that the time being stirred to react in the step (1) is 1-3 Hour.

Technical field

The present invention relates to technical field of organic synthesis, and in particular to a kind of restoring method of nitroolefin.

Background technique

In organic synthesis, aliphatic nitro compound is with important value and widely used structural unit and centre Body.Restoring nitroolefin and obtaining aliphatic nitro compound is relatively conventional method.

Above-mentioned reaction is a simple double bond reduction reaction, but under the alkaline condition that sodium borohydride and alcohol are formed, is changed Michael addition can be occurred by closing object 2 and compound 1, generate dimerization impurity.

In addition it has been reported that (J.Org.Chem., 1967,32,4134-4136), after raw material is dissolved in acetonitrile, adjusts pH to 3- 6, then be added drop-wise in the aqueous solution of sodium borohydride, which has better effects to alkyls alkene nitro, but to aromatic ring class substrate, until Rare 30% dimerization impurity generates.

G.W.Kabalka etc. (Tetrahedron, 1990,46,7443-7457) compared 3-sec-butyl lithium borohydride, contain The exchanger resin of sodium borohydride and methanol/Tetrahydrofuran System of sodium borohydride find the exchanger resin result containing sodium borohydride More excellent, highest yield is 83%.

Document report (Chem.Commun., 2016,52,8361-8364) only uses sodium borohydride and ethyl alcohol, with 78% yield Obtain product.But the reaction needs the ethyl alcohol (quality of relative substrate, g) of 46 times of volumes (mL), substantially reduces industrial production Power.We use 10 times of volume (mL) ethyl alcohol (quality of relative substrate, g) simultaneously, repeat above-mentioned experimental procedure, and discovery has The dimerization impurity of 29.55% (HPLC purity) generates.

Above-mentioned restoring method is for industrialized production, higher cost, at the same dimerization impurity content it is higher cause yield compared with It is low.

Summary of the invention

The technical problem to be solved by the present invention is to how overcome drawbacks described above existing in the prior art, a kind of be applicable in is provided In industrial restoring method.

To solve the above problems, the present invention provides a kind of restoring method of nitroolefin, it is molten using alcohol and water as mixing Agent, for metallic boron hydrides as hydrogen source, reduction nitroolefin is nitroparaffins.

Specifically comprise the following steps:

Step (1): compound 1 is added in alcohol/water mixed solvent, and at 0-50 DEG C, reducing agent metal boron hydrogen is added Compound is stirred to react；

Step (2): being concentrated into constant weight for step (1) resulting solution, and ethyl acetate and saturation chlorine are added into concentrate Change ammonium salt solution；

Step (3): liquid separation obtains upper layer ethyl acetate layer, dry, is concentrated into constant weight and obtains reduzate compound 2.

R in compound 1 and compound 2₁Any one in C1-C8 straight chained alkyl and general formula functional group 1, R₂For Hydrogen or methyl, R₃、R₄、R₅、R₆、R₇It is each independently selected from one of hydrogen, methyl, methoxyl group or hydroxyl.

Alcohol in the step (1) is one of methanol, ethyl alcohol, normal propyl alcohol and isopropanol；

Alcohol/the water mixed solvent is according to alcohol: water volume ratio is (2-10): 1 is obtained by mixing, preferred alcohols: water volume ratio For (3-4): 1；Mixed solvent dosage and the ratio of compound 1 are (5-30) mL:1g, preferably (5-10) mL:1g.

Further, the metallic boron hydrides in the step (1) is lithium borohydride, sodium borohydride, potassium borohydride and boron One of zinc hydride.

Further, the molar ratio of metallic boron hydrides and compound 1 is (0.5-3) in step (1): 1, preferably (1.0-1.5): 1.

Further, the time being stirred to react in the step (1) is 1-3 hours.

Further, extractant ethyl acetate dosage described in step (2): saturated ammonium chloride solution dosage: step (1) Described in compound 1 dosage ratio be (2-10) mL:(2-10) mL:1g, preferably (3-5) mL:(2-4) mL:1g.

If only making solvent with alcohol in reaction, metallic boron hydrides such as sodium borohydride and alcohol generate sodium alkoxide (such as formula 1), entirely Reaction system causes Michael addition adducts dimerization impurity to generate at strong basicity；And after water is added, sodium borohydride can preferentially and water Reaction, kodalk (such as formula 2) alkalinity of generation are weaker than sodium alkoxide.Another possible cause is that kodalk is insoluble in alcohol and in water In solubility it is limited so that part be precipitated, cause substrate alkaline condition collision probability reduce.

NaBH₄+ 4HOR=B (OR)₃+4H₂↑+NaOR (R=Me, Et, n-Pr, i-Pr) (formula 1)

NaBH₄+2H₂O=NaBO₂+4H₂↑ (formula 2)

Compared with prior art, the method for the present invention has the following advantages and beneficial effects:

1, the present invention provides a kind of restoring method of nitroolefin, by the way that a certain amount of water is added into reaction solution, can incite somebody to action Dimerization Control of Impurities 3.0% (HPLC purity) below.Need not move through column chromatography, aliphatic or aromatic nitro compound HPLC purity can control 95.0% or more.

2, synthetic method of the invention is applicable in aromatic ring and linear paraffin.

3, synthetic method cost of material of the invention is cheap, and input cost is low and environmental-friendly, is suitable for industrialized production.

Detailed description of the invention

Fig. 1 is the spectrogram that the reduzate that embodiment 2 obtains detects purity with HPLC.

Fig. 2 is the spectrogram that the reduzate that embodiment 4 obtains detects purity with HPLC.

Fig. 3 is the spectrogram that the reduzate that embodiment 5 obtains detects purity with HPLC.

Specific embodiment

The technical schemes of the invention are described in detail in conjunction with specific embodiments by applicant below, it should be noted that being described below Embodiment be exemplary, for explaining only the invention, and cannot be understood to want right of the present invention in what degree in office Ask book that the limitation of range is claimed.In addition, all raw materials employed in the following examples are equal if do not clearly stated It is commercially available in the market, or is referred to document or the synthesis of known method, for the reaction condition that do not list, It also is what those skilled in the art were easy to get.