CN105111086A - 1-phenyl-2-nitroethanol and preparation method of derivatives thereof - Google Patents

1-phenyl-2-nitroethanol and preparation method of derivatives thereof Download PDF

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CN105111086A
CN105111086A CN201510048080.2A CN201510048080A CN105111086A CN 105111086 A CN105111086 A CN 105111086A CN 201510048080 A CN201510048080 A CN 201510048080A CN 105111086 A CN105111086 A CN 105111086A
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phenyl
derivative
nitroethyl alcohol
preparation
nitroethyl
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焦岩
张明道
陈敏东
章翔宇
郑江
李守光
张海英
秦芳莲
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Nanjing University of Information Science and Technology
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Nanjing University of Information Science and Technology
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Abstract

The invention discloses a 1-phenyl-2-nitroethanol and a preparation method of derivatives thereof, and the method employs potassium tert-butoxide or sodium tert-butoxide as a catalyst for catalysis of various benzaldehyde derivatives and nitromethane or nitroethane for preparing 1-phenyl-2-nitroethanol and derivatives thereof. The preparation of the invention has the advantages of good catalyst effect, high synthesis reaction conversion rate, high yield which is 50-90%, low cost of crystallization or extraction method for separating, simple operation, non-pollution due to inorganic base catalysis, and good practicality.

Description

The preparation method of a kind of 1-phenyl-2-nitroethyl alcohol and derivative thereof
Technical field
The present invention relates to technical field, is the preparation method of a kind of 1-phenyl-2-nitroethyl alcohol and derivative thereof specifically.
Background technology
Beta-alkamine medicine is common natural product and marketed drug, the compound with aryl beta-amino ethanol is a kind of adrenoceptor agonists class medicine, such as Salmeterol, salbutamol all has 1-phenyl-2-amino alcohol structure, be respectively used to Cardiovarscular and respiratory tract disease, and beta-alkamine can be obtained by the reduction of β-nitroalcohol, the people (Zhou Di such as such as Zhou Di, Liu Juntao, Lu Yixiang, Jia Xian, Li Xingshu. Chinese pharmaceutical chemistry magazine the 19th volume .2009, Vol.19, No2, 123-126) prepare Salmeterol by the method.
The preparation of β-nitroalcohol has come mainly through Henry reaction, and be applied at present Henry reaction catalyzer on be mainly divided into mineral alkali, organic bases and a metal-organic complex three kinds, and really can be applied to industrial main or mineral alkali and small molecules organic bases compounds, because it is with low cost, pollute little, as materials such as sodium hydroxide, salt of wormwood, sodium methylate and triethylamines.But in the process using these catalyzer, we find the problem that ubiquitous catalytic effect is undesirable, and productive rate is low, and product should not be purified.Therefore select a kind of catalyzer of excellent catalytic effect, and to study its reaction process be that can it key of widespread use.
Summary of the invention
The object of the invention is for above-mentioned deficiency of the prior art, the present invention have studied with potassium tert.-butoxide or sodium tert-butoxide as the various benzaldehyde derivative of catalyst and Nitromethane 99Min. or nitroethane are to prepare the method for 1-phenyl-2-nitroethyl alcohol and derivative thereof, reaction thoroughly, aftertreatment is simply efficient, is expected to the requirement meeting industry member production.
The object of the invention is to be achieved through the following technical solutions:
A preparation method for 1-phenyl-2-nitroethyl alcohol and derivative thereof, it uses potassium tert.-butoxide or sodium tert-butoxide catalysis Henry reaction to be prepared, and its reaction expression is: (see figure 1)
In formula: R=H, Br, Cl, OMe;
R’=H、Me。
The derivative of above-mentioned 1-phenyl-2-nitroethyl alcohol comprises 1-(2,4-dichloro) phenyl-2-nitroethyl alcohol, 1-(3-nitro) phenyl-2-nitroethyl alcohol, 1-(3-bromine) phenyl-2-nitroethyl alcohol, 1-(4-methoxyl group) phenyl-2-nitroethyl alcohol, 1-phenyl-2-nitro-propanol and 1-(2,4-dichloro) phenyl-2-nitro-propanol.Their chemical molecular structure is as following table:
The concrete operation step of above-mentioned preparation method is as follows:
(1) potassium tert.-butoxide or sodium tert-butoxide are dissolved in the trimethyl carbinol and are mixed with the t-butanol solution that concentration is 0.1-0.4mol/L,
(2) mix according to the ratio of t-butanol solution with the volume ratio 1-4:1 of tetrahydrofuran (THF), form mixed solution;
(3) add nitroparaffins while stirring in the mixed solution obtained to step 2, being mixed with concentration is 3-8mol/L a nitroparaffin solution;
(4) drip benzaldehyde derivative, stirred at ambient temperature 4-8h in a nitroparaffin solution obtained to step 3, the mol ratio of nitroparaffins and benzaldehyde derivative is 5-10:1;
(5) in step 4, reaction isolates crystallization after terminating, and is carried out washing by the saturated sodium sulfite solution of crystallization, anhydrous magnesium sulfate drying, evaporate to dryness obtain 1-phenyl-2-nitroethyl alcohol or derivatives thereof.
Above-mentioned nitroparaffins are Nitromethane 99Min. or nitroethane.
Above-mentioned benzaldehyde derivative is 2,4 dichloro benzene formaldehyde or m-nitrobenzaldehyde or 4-methoxybenzaldehyde or 3-bromobenzaldehyde.
The method of Crystallization Separation described in step 5 can adopt add water crystallization method or extraction into ethyl acetate method.
the present invention has following outstanding beneficial effect:
The preparation method of 1-phenyl-2-nitroethyl alcohol of the present invention and derivative thereof, catalyst effect is strong, and building-up reactions transformation efficiency is high, productive rate 50-90%, and be separated and adopt crystallization or extraction process, cost is low, easy and simple to handle, mineral alkali catalysis, pollution-free, and practicality is good.
accompanying drawing illustrates:
The reaction expression of the preparation method of Fig. 1 1-phenyl of the present invention-2-nitroethyl alcohol and derivative thereof;
Fig. 2 is that embodiment 1 obtains product 1hNMR(proton nmr spectra) detected result collection of illustrative plates;
Fig. 3 is ESI-MS mass spectrum (electron spray ionisation) the detected result collection of illustrative plates that embodiment 1 obtains product;
Fig. 4 is that embodiment 2 obtains product 1hNMR detected result collection of illustrative plates;
Fig. 5 is that embodiment 3 obtains product 1hNMR detected result collection of illustrative plates;
Fig. 6 is that embodiment 4 obtains product 1hNMR detected result collection of illustrative plates;
Fig. 7 is that embodiment 5 obtains product 1hNMR detected result collection of illustrative plates;
Fig. 8 is that embodiment 6 obtains product 1hNMR detected result collection of illustrative plates;
Fig. 9 is that embodiment 7 obtains product 1hNMR detected result collection of illustrative plates.
Embodiment
Below in conjunction with drawings and Examples, the invention will be further described:
embodiment 1:
Preparation 1-(2,4-dichloro) phenyl-2-nitroethyl alcohol
15mLt-BuONa/t-BuOH solution (containing t-BuONa2mmol) and 15mLTHF is added in 100mL flask, 10.8mL (0.2mol) Nitromethane 99Min. is added under stirring, stir in a moment, add 3.5g (20mmol) 2 in batches, 4-dichlorobenzaldehyde, stirred at ambient temperature reaction 5h.TLC(thin-layer chromatography) monitoring react completely after, add 30mL saturated ammonium chloride solution and 40mL ethyl acetate, stir 10 minutes.After separatory, aqueous phase 30mL*2 extraction into ethyl acetate, merges organic phase, twice is washed with the saturated metabisulfite solution of 30mL, anhydrous magnesium sulfate drying, filter, steaming desolventizes, obtain nearly colorless oil, room temperature places after product crystallization in 4 hours, vacuum-drying under normal temperature, obtains 4.2g micro-yellow powder shape solid, productive rate 90%, the m.p.(fusing point of micro-yellow powder shape solid) be 78 ~ 80 oc.In addition, post-treating method also can adopt directly to be poured in frozen water by reaction solution, collects lower floor's oil droplet, is placed in air crystallization. 1hNMR(proton nmr spectra) (500MHz, CDCl 3) analytical results be (see figure 2): δ 7.62 (d, 1H, j=8.5Hz, Ar-H), 7.41 (d, 1H, j=1.5Hz, Ar-H), 7.32 (dd, 1H, j=1.5Hz, 8.5Hz, Ar-H), 5.80 (d, j=9.5Hz, 1H, CH-O), 4.65 (dd, j=13.5Hz, 2Hz, 1H ,-CH 2-), 4.20 (dd, j=9.5Hz, 13.5Hz, 1H ,-CH 2-), 3.01 (d, j=4Hz, 1H ,-OH).ESI-MS mass spectrum (electron spray ionisation) analytical results is (see figure 3): calculatedC 8h 7cl 2nO 3, 236.05, found236.0.Prove that the micro-yellow powder shape solid obtained is 1-(2,4-dichloro) phenyl-2-nitroethyl alcohol.
embodiment 2:
Preparation 1-phenyl-2-nitroethyl alcohol
Substitute 3.5g (20mmol) 2,4 dichloro benzene formaldehyde with 2.1g (20mmol) phenyl aldehyde to react with Nitromethane 99Min., synthetic method is with embodiment 1, and product is oily matter, productive rate 70%. 1hNMR (500MHz, CDCl 3) analytical results is (see figure 4): δ 7.41 – 7.35 (m, 5H, Ar-H), 5.45 (dd, j=10,3Hz, 1H, CH-O), 4.60 (dd, j=13.5Hz, 10Hz, 1H ,-CH 2-), 4.51 (dd, j=13.5Hz, 3Hz, 1H ,-CH 2-), 2.73 (bs, 1H ,-OH).Prove that the oily matter obtained is 1-phenyl-2-nitroethyl alcohol.
embodiment 3:
Preparation 1-(3-nitro) phenyl-2-nitroethyl alcohol
In 100mL flask, add the t-BuOK(2.7mmol of 0.03g), t-BuOH/THF, 1.5mL(28mmol of 5mL) Nitromethane 99Min., stir.By 0.42g(2.8mmol) m-nitrobenzaldehyde be dissolved in the THF of 1.5mL, dropwise join in single port bottle, react under normal temperature and pressure.TLC tracing detection, after reacting completely, adds 20mL distilled water and 30mLEtOAc(ethyl acetate in system), stir separatory, aqueous phase 20mLEtOAc extracts 2 times, and after merging organic phase, the saturated NaCl of organic phase 30mL washs 2 times, anhydrous MgSO 4drying, steaming desolventizes and obtains 0.95g pale yellow oil.Purify with PE recrystallization and obtain 0.51g faint yellow solid.Productive rate 86%.Faint yellow solid m.p.(fusing point) be 75-76 oC. 1hNMR (500MHz, CDCl 3) analytical results is (see figure 5): δ 8.32 (s, 1H, Ar-H), 8.23 (d, 1H, j=14Hz, Ar-H), 7.78 (d, 1H, j=13Hz, Ar-H), 7.62 (t, 1H, j=14Hz, 13Hz, Ar-H), 5.61 (m, 1H, CH-O), 4.61 (m, 2H ,-CH 2-), 3.23 (s, 1H ,-OH).Prove that the faint yellow solid obtained is 1-(3-nitro) phenyl-2-nitroethyl alcohol.
embodiment 4:
Preparation 1-(4-methoxyl group) phenyl-2-nitroethyl alcohol
Substitute 3.5g (20mmol) 2,4 dichloro benzene formaldehyde with 2.7g (20mmol) 4-methoxybenzaldehyde to react with Nitromethane 99Min., all the other synthetic methods are with example 1, and product is oily matter, productive rate 46%. 1hNMR (500MHz, CDCl 3) analytical results be (see figure 6): δ 7.32 (d, j=14Hz, 2H, Ar-H), 6.92 (d, j=14Hz, 2H, Ar-H), 5.41 (dd, j=15Hz, 5Hz, 1H, CH-O), 4.60 (dd, j=16Hz, 22Hz, 1H ,-CH 2-), 4.48 (dd, j=22Hz, 5Hz, 1H ,-CH 2-), 3.79 (s, 3H), 2.71 (bs, 1H ,-OH).Prove that the oily matter obtained is 1-(4-methoxyl group) phenyl-2-nitroethyl alcohol.
embodiment 5:
Preparation 1-(3-bromine) phenyl-2-nitroethyl alcohol
Substitute 3.5g (20mmol) 2,4 dichloro benzene formaldehyde with 3.7g (20mmol) 3-bromobenzaldehyde to react with Nitromethane 99Min., all the other synthetic methods are with example 1, and product is oily matter, productive rate 86%. 1hNMR (500MHz, CDCl 3) analytical results is (see figure 7): δ 7.59 (s, 1H, Ar-H), 7.49 (d, 1H, j=13Hz, Ar-H), 7.25-7.34 (m, 2H, Ar-H), 5.44 (dd, j=15Hz, 5Hz, 1H, CH-O), 4.48-4.67 (m, 2H ,-CH 2-), 3.00 (bs, 1H ,-OH).Prove that the oily matter obtained is 1-(3-bromine) phenyl-2-nitroethyl alcohol.
embodiment 6:
Preparation 1-phenyl-2-nitro-propanol
Synthetic method is with example 1, and substitute 3.5g (20mmol) 2,4 dichloro benzene formaldehyde with 2.1g (20mmol) phenyl aldehyde, and substitute Nitromethane 99Min. as raw material reaction using 0.1mol nitroethane, product is oily matter, productive rate 76%. 1hNMR (500MHz, CDCl 3) analytical results is (see figure 8):
anticonfiguration: δ 7.33 (m, 5H, Ar-H), 5.35 (d, j=5.5Hz, 1H, CH-O), 4.70 (m, 1H ,-CH 2-), 1.51 (d, 3H ,-Me).
synconfiguration: δ 7.33 (m, 7.75H, Ar-H), 5.05 (d, j=15Hz, 1.75H, CH-O), 4.77 (m, 1.75H ,-CH 2-), 1.28 (d, 5.25H ,-Me).
From 1hNMR analytical results is known: 1-phenyl-2-nitro-propanol is antiwith synthe mixture of two kinds of structures, according to 1hNMR integration is 1:1.7 than calculating its content mol ratio.
embodiment 7:
Synthetic method is with example 1, and substitute 10.8mL (0.2mol) Nitromethane 99Min. with 3.5g (20mmol) nitroethane and come with 2,4 dichloro benzene formaldehyde for raw material reaction, product is light yellow oil, productive rate 60%. 1hNMR (500MHz, CDCl 3) analytical results is (see figure 9):
anticonfiguration: δ 7.60 (d, j=14Hz, 1H, Ar-H), 7.43 (d, j=3Hz, 1H, Ar-H), 7.35 (t, j=3Hz, 3.5Hz, 1H, Ar-H), 5.80 (s, 1H, CH-O), 4.83 (m, 1H ,-CH 2-), 2.90 (d, j=5.5Hz, 1H ,-OH), 1.47 (d, j=11.5Hz, 3H ,-Me).
synconfiguration: δ 7.46 (d, j=14Hz, 0.90H, Ar-H), 7.40 (d, j=3Hz, 0.90H, Ar-H), 7.33 (t, j=3Hz, 3.5Hz, 0.90H, Ar-H), 5.55 (m, 0.90H, CH-O), 4.83 (m, 0.90H ,-CH 2-), 2.81 (d, j=8.5Hz, 0.90H ,-OH) 1.44 (d, j=11.5Hz, 2.7H ,-Me).
From 1hNMR analytical results is known: 1-(2,4-dichloro) phenyl-2-nitro-propanol is antiwith synthe mixture of two kinds of structures, according to 1hNMR integration is 1:0.9 than calculating its content mol ratio.
Be more than preferred embodiment of the present invention, all changes done according to technical solution of the present invention, when the function produced does not exceed the scope of technical solution of the present invention, all belong to protection scope of the present invention.

Claims (6)

1. a preparation method for 1-phenyl-2-nitroethyl alcohol and derivative thereof, is characterized in that, the method uses potassium tert.-butoxide or sodium tert-butoxide catalysis Henry reaction to be prepared, and its reaction expression is:
In formula: R=H, Br, Cl, OMe;
R’=H、Me。
2. the preparation method of 1-phenyl-2-nitroethyl alcohol according to claim 1 and derivative thereof, it is characterized in that, the derivative of described 1-phenyl-2-nitroethyl alcohol comprises 1-(2,4-dichloro) phenyl-2-nitroethyl alcohol, 1-(3-nitro) phenyl-2-nitroethyl alcohol, 1-(3-bromine) phenyl-2-nitroethyl alcohol, 1-(4-methoxyl group) phenyl-2-nitroethyl alcohol, 1-phenyl-2-nitro-propanol and 1-(2,4-dichloro) phenyl-2-nitro-propanol.
3. the preparation method of 1-phenyl-2-nitroethyl alcohol according to claim 1 and derivative thereof, it is characterized in that, concrete operation step is:
(1) potassium tert.-butoxide or sodium tert-butoxide are dissolved in the trimethyl carbinol and are mixed with the t-butanol solution that concentration is 0.1-0.4mol/L,
(2) mix according to the ratio of t-butanol solution with the volume ratio 1-4:1 of tetrahydrofuran (THF), form mixed solution;
(3) add nitroparaffins while stirring in the mixed solution obtained to step 2, being mixed with concentration is 3-8mol/L a nitroparaffin solution;
(4) drip phenyl aldehyde or benzaldehyde derivative, stirred at ambient temperature 4-8h in a nitroparaffin solution obtained to step 3, the mol ratio of nitroparaffins and phenyl aldehyde or benzaldehyde derivative is 5-10:1;
(5) in step 4, reaction isolates crystallization after terminating, and is carried out washing by the saturated sodium sulfite solution of crystallization, anhydrous magnesium sulfate drying, evaporate to dryness obtain 1-phenyl-2-nitroethyl alcohol or derivatives thereof.
4. the preparation method of 1-phenyl-2-nitroethyl alcohol according to claim 3 and derivative thereof, is characterized in that, described nitroparaffins are Nitromethane 99Min. or nitroethane.
5. the preparation method of 1-phenyl-2-nitroethyl alcohol according to claim 3 and derivative thereof, is characterized in that, described benzaldehyde derivative is 2,4 dichloro benzene formaldehyde or m-nitrobenzaldehyde or 4-methoxybenzaldehyde or 3-bromobenzaldehyde.
6. the preparation method of 1-phenyl-2-nitroethyl alcohol according to claim 3 and derivative thereof, is characterized in that, the method for Crystallization Separation described in step 5 adopts crystallization method or the extraction into ethyl acetate method of adding water.
CN201510048080.2A 2015-01-30 2015-01-30 1-phenyl-2-nitroethanol and preparation method of derivatives thereof Pending CN105111086A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109096117A (en) * 2018-09-25 2018-12-28 南京信息工程大学 The preparation method of 1- phenyl -2- nitroethyl alcohol and its derivative

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SCOTT E. DENMARK等: "Inter- and Intramolecular [4+2] Cycloadditions of Nitroalkenes with Olefins. 2-Nitrostyrenes", 《J. ORG. CHEM.》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109096117A (en) * 2018-09-25 2018-12-28 南京信息工程大学 The preparation method of 1- phenyl -2- nitroethyl alcohol and its derivative
CN109096117B (en) * 2018-09-25 2020-12-25 南京信息工程大学 Preparation method of 1-phenyl-2-nitroethanol and derivatives thereof

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