CN101863915A - N,N-bissubstituted-O-trialkyl silicon-based hydroxylamine compound and preparation thereof - Google Patents
N,N-bissubstituted-O-trialkyl silicon-based hydroxylamine compound and preparation thereof Download PDFInfo
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Abstract
The invention provides a novel hydroxylamine compound, i.e. N,N-bissubstituted-O-trialkyl silicon-based hydroxylamine compound, belonging to the technical field of chemical synthesis. The compound is prepared by the steps of: firstly, reacting nitryl hydrocarbon materials in an ammonium chloride water solution with zinc powder to generate N-alkyl hydroxylamine; secondly, reacting the N-alkyl hydroxylamine with an aldehydes compound in organic solvent to generate nitrone; and thirdly, reacting the nitrone with organic metal reagent in the promotion of trialkyl silicon haloganide. The N,N-bissubstituted-O-trialkyl silicon-based hydroxylamine compound can remove silicon base to obtain the hydroxylamine compound, and the hydroxylamine compound is reduced to obtain an amine compound. The preparation method of the N,N-bissubstituted-O-trialkyl silicon-based hydroxylamine compound has the advantages of easily obtained and low cost raw materials, mild reaction condition, high yield, convenient operation, and the like.
Description
Technical field
The invention belongs to chemosynthesis technical field, relate to a kind of hydroxylamine compound, relate in particular to a kind of N, two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-and preparation method thereof.
Background technology
The nitrogen-oxygen-silicon ether compound is the polyfunctional compound with multiple using value, as with the erythromycin oximate, so that etherificate and found erythromycin of new generation---Roxithromycin (Bioorg.Med.Chem.Lett.2006,569-572).In addition, this compounds further desiliconization ether and azanol, reduction can get aminated compounds, thereby N, two replacement-O-trialkyl the silicon-based hydroxylamine compounds of N-are N, disubstituted azanol of N-and N, the synthetic intermediate very easily of N-bis substituted amine compounds.
N, the two substituted hydroxylamine compounds of N-also are the important organic intermediates that is widely used in key areas such as chemical industry, pesticide industry, medicine industry and dyestuffs industries.For example TEMPOL is the free-radical scavengers that is widely known by the people, and brings into play anti-inflammatory action in several animal models such as oxidative damage and inflammation.N-oxidation piperidines can be used for treating because the disease that causes of oxyradical and as food and beauty treatment additive (United States Patent (USP) 5,981,548).The nucleosides of N-alkyl azanol class is found has anti-HIV characteristic (Chinese patent 200410060498.7).For example N-tertiary butyl azanol is one of critical materials of the synthetic N-tertiary butyl-α-phenyl nitrone (PBN) again.This class N-tertiary butyl-α-the phenyl nitrone is one of radical scavenger that is most widely used, and has protection brain cell, the anti-ageing multiple function of waiting for a long time [chemistry circular, 1989,10:1-016].In addition, hydroxylamine compound also is widely used in the organic synthesis, for example, can synthesize materials such as oxime, nitrone with carbonyl compound effects such as aldehyde, ketone, effects such as continuation and organometallic reagent or undersaturated alkene can prepare the polysubstituted azanol and the aminated compounds of multiple structure.
Summary of the invention
The purpose of this invention is to provide a kind of N, the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-.
Another object of the present invention provides a kind of N, the preparation method of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-.
(1) N, the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-, its structure is shown below:
R
1Be alkyl, aromatic base or heterogeneous ring compound;
R
2Be alkyl, aromatic base or heterogeneous ring compound;
R
3Be alkyl, aromatic base or heterogeneous ring compound;
R
4Be alkyl, aromatic base.
R
1, R
2, R
3, R
4Structure can be identical, also can be different.
Described alkyl can be the straight or branched alkyl substituent, and preferred C1-C10 alkyl is as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl etc.
Described aromatic base can be aromatic groups such as phenyl, naphthyl or anthryl, also can be the aromatic group that has substituting group (as halogen, alkoxyl group, alkyl, nitro, cyano group, acyl group).When aromatic base has substituting group, R
1, R
2, R
3, R
4Can be with different substituting groups, also can be with identical substituting group, and also substituent position and number on phenyl ring is not subjected to foregoing structural limitations.
In view of N, the huge applications of the two substituted hydroxylamine compounds of N-in medicine and organic synthesis is worth, N provided by the present invention, and the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-have structure diversity, can carry out structural adjustment easily.In addition this class material can desiliconization ether protecting group and azanol, reduction and amine, therefore be particularly suitable for making up N, two substituted hydroxylamines of N-or N, N-disubstituted amines compound library carries out medicament high flux screening.
(2) N, the preparation of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-
N of the present invention, the preparation method of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-comprises following processing step:
1. the preparation of N-substituted hydroxylamine: in the solution of ammonium chloride, with nitro-hydrocarbon and zinc powder with 1: 1～1: 5 mol ratio (preferred proportion 1: 2) mixing, react 1～8 hour (preferred 2 hours) down in 60～75 ℃, filter, washing adds sodium-chlor and makes solution become supersaturated solution, cooling, separate out the crude product of N-Phenylhydroxylamine, crude product obtains N-substituted hydroxylamine compound with methylene dichloride and sherwood oil recrystallization.
The concentration of described ammonium chloride solution is 0.3～0.5g/ml.
Described nitro-hydrocarbon is nitroparaffins or nitro-aromatic.
2. the preparation of nitrone: in organic solvent, N-substituted hydroxylamine compound is mixed with 1: 1～2: 1 mol ratio (preferred 1: 1.2) with aldehyde compound, react 3～9 hours (preferred 4 hours) down in 0～80 ℃ (preferred 65 ℃), the pressure reducing and steaming solvent, obtain crude product, with crude product ethyl acetate and sherwood oil recrystallization, obtain nitrone again.
Described aldehyde compound comprises that alkanoic (as formaldehyde, acetaldehyde, butyraldehyde, phenylacrolein etc.) or aromatic aldehyde are (as phenyl aldehyde, aubepine, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, 3,4,5-TMB, 2,4 dichloro benzene formaldehyde, 2 furan carboxyaldehyde, 2 thiophene carboxaldehyde etc.).
Described organic solvent is protic solvent (as ethanol, acetate, an ethamine etc.), also can be non-protonic solvent (as tetrahydrofuran (THF), 1,4-dioxane, benzene,toluene,xylene, methylene dichloride etc.); Preferred solvent is a dehydrated alcohol.
3. N; the preparation of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-: under nitrogen protection; in non-proton organic solvent; nitrone, organometallic reagent, trialkyl halosilanes are mixed with 1: 1: 1～1: 2: 2 mol ratio (preferred 1: 1.5: 1.5); in reacting 1～10 hour (preferred 5 hours) down at 0～60 ℃ (preferred 30 ℃); saturated ammonium chloride solution cancellation; ethyl acetate extraction; anhydrous magnesium sulfate drying; the pressure reducing and steaming organic solvent; column chromatography for separation obtains N, the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-.
Described organometallic reagent is organolithium, organic-magnesium, organic zinc, organic copper, organic sodium or organosilicon etc.;
Hydrocarbon in the described trialkyl halosilanes is an aliphatic hydrocarbon, as methyl, ethyl, butyl etc., also can be aromatic hydrocarbon, as aromatic hydrocarbon such as phenyl, benzyls.Halogen is the arbitrary halogen in chlorine, bromine, iodine, the fluorine in the trialkyl halosilanes.
The hydroxylamine compound of the present invention's preparation, the detection through detection meanss such as NMR (Nuclear Magnetic Resonance) spectrum, infrared spectra, mass spectrums shows that its structure is consistent with re-set target, proves that the synthetic of phenylethylamine compounds is successful.
N provided by the invention, the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-can further be reduced to aminated compounds.
The present invention utilizes organometallic reagent and nitrone under the promotion of trialkyl halosilanes, one-step synthesis N, and the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-have advantages such as raw material is cheap and easy to get, reaction conditions is gentle, productive rate is high, easy to operate.
Embodiment
To N of the present invention, the preparation of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-is described further below by concrete experimental example.
The preparation of embodiment 1:N-phenyl-N-(trimethyl silicon based)-1-phenyl-2-phenyl-ethyl amine
(1) N-Phenylhydroxylamine is synthetic
Under the condition of room temperature, with oil of mirbane (10g, 81.3mmol), ammonium chloride (5.2g, 97.6mmol) and water (160ml) add in the round-bottomed flask of 250ml, behind the vigorous stirring 10min, be heated to 60 ℃, add then in batches zinc powder (10.57g, 162.6mmol), in one hour, add, because this reaction is thermopositive reaction, add zinc powder during allowable temperature rise, but can not be above 75 ℃.After zinc powder adds, continue reaction 1 hour again, filtered while hot with 40 ℃ of warm water (20ml) washing filter residue, adds sodium-chlor then in filtrate, make solution become supersaturated solution, promptly there is yellow needle-like crystal to separate out after the cooling, is the crude product of N-Phenylhydroxylamine, crude product methylene dichloride and sherwood oil recrystallization, can obtain pure pyridyl azanol 7 grams, productive rate 78%.
Reaction equation is as follows:
(2) α-phenyl-N-phenyl nitrone is synthetic
Under protection of nitrogen gas; with N-Phenylhydroxylamine (1.09g; 10.0mmol) (1.27g 12mmol) is dissolved in the dehydrated alcohol (20ml), is heated to about 65 ℃ with phenyl aldehyde; reacted 4 hours; the pressure reducing and steaming solvent obtains crude product, again with crude product ethyl acetate and sherwood oil recrystallization; can obtain product 1.69 grams, productive rate 86%.Fusing point: 109-110 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (CDCl
3, 400MHz), δ (ppm): 7.45-7.51 (m, 6H), 7.78 (dd, J=9.2,2.4Hz, 2H), 7.92 (s, 1H), 8.39-8.41 (m, 2H).
(3) N-phenyl-N-(trimethyl silicon based)-1-phenyl-2-phenyl-ethyl amine is synthetic
To be dissolved in α-phenyl-N-phenyl nitrone (0.35g of tetrahydrofuran (THF) (10ml); 1.77mmol); slowly be added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol); to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the round-bottomed flask; under nitrogen protection, be heated to about 30 ℃; reacted 5 hours; the saturated ammonium chloride solution that adds 15ml carries out cancellation; with the ethyl acetate extraction of 50ml, use the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent; column chromatography for separation obtains product 0.48 gram, productive rate 75%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3) δ (ppm): 0.15 (s, 9H), 3.50 (dd, J=13.7,10.2Hz, 1H), 3.56 (dd, J=13.7,4.2Hz, 1H), 4.70 (dd, J=10.2,4.3Hz, 1H), 7.18-7.21 (m, 2H), 7.25 (tt, J=7.1,1.4Hz, 1H), 7.32 (tt, J=7.4,1.2Hz, 4H), 7.39-7.45 (m, 6H), 7.48 (s, 2H).
Synthesizing of example 2:N-phenyl-N-(trimethyl silicon based)-1-(4-p-methoxy-phenyl)-2-phenyl-ethyl amine
(1) with embodiment 1 step (1)
(2) α-(4-p-methoxy-phenyl)-N-phenyl nitrone is synthetic
With N-Phenylhydroxylamine (1.09g; 10.0mmol) and aubepine (1.63g; 12mmol) be dissolved in the dehydrated alcohol (20ml); under protection of nitrogen gas, be heated to about 65 ℃, reacted the pressure reducing and steaming solvent 4 hours; obtain crude product; crude product with ethyl acetate and sherwood oil recrystallization, can be obtained product 2.08 grams, productive rate 92%.Fusing point: 115～116 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 3.88 (s, 3H), 7.00 (d, J=9.0Hz, 2H), 7.42-7.50 (m, 3H), 7.77 (dd, J=8.4,1.7Hz, 2H), 7.86 (s, 1H), 8.41 (d, J=9.0Hz, 2H).
(3) N-phenyl-N-(trimethyl silicon based)-1-(4-p-methoxy-phenyl)-2-phenyl-ethyl amine is synthetic
To be dissolved in α-(4-methoxyphenyl)-N-phenyl nitrone (0.43g of tetrahydrofuran (THF) (10ml); 1.77mmol); slowly be added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol); to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the above-mentioned flask; under nitrogen protection, be heated to about 30 ℃; reacted 5 hours; the saturated ammonium chloride solution that adds 15ml carries out cancellation; with the ethyl acetate extraction of 50ml, use the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent; column chromatography for separation obtains product 0.46 gram, productive rate 67%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.15 (s, 9H), 3.42 (dd, J=13.6,10.7Hz, 1H), 3.53 (dd, J=13.8,3.9Hz, 1H), 3.90 (s, 3H), 4.64 (dd, J=10.6,3.9Hz, 1H), 6.90 (d, J=8.4Hz, 2H), 7.17 (dd, J=7.4,0.9Hz, 3H), 7.24 (d, J=6.2Hz, 1H), 7.29 (t, J=13.7Hz, 6H), 7.40 (dd, J=10.8,2.9Hz, 2H).
Synthesizing of example 3:N-phenyl-N-(trimethyl silicon based)-1-(4-chloro-phenyl-)-2-phenyl-ethyl amine
(1) with embodiment 1 step (1)
(2) α-(4-chloro-phenyl-)-N-phenyl nitrone is synthetic
Under protection of nitrogen gas; with N-Phenylhydroxylamine (1.09g; 10.0mmol) (1.69g in the dehydrated alcohol that 12mmol) is dissolved in (20ml), is heated to about 65 ℃ with 4-chloro-benzaldehyde; reacted 4 hours; the pressure reducing and steaming solvent gets crude product, with crude product ethyl acetate and sherwood oil recrystallization; can obtain product 2.03 grams, productive rate 88%.Fusing point: 152-153 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl3), δ (ppm): 7.44-7.50 (m, 5H), 7.75-7.79 (m, 2H), 7.91 (s, 1H), 8.36 (d, J=8.5Hz, 2H).
(3) N-phenyl-N-(trimethyl silicon based)-1-(4-chloro-phenyl-)-2-phenyl-ethyl amine is synthetic
(0.41g 1.77mmol) slowly is added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol) will to be dissolved in α-(4-chloro-phenyl-)-N-phenyl nitrone of tetrahydrofuran (THF) (10ml); To be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the above-mentioned flask; under nitrogen protection, be heated to about 30 ℃; reacted 5 hours, the saturated ammonium chloride solution that adds 15ml carries out cancellation, with the ethyl acetate extraction of 50ml; use the anhydrous magnesium sulfate drying of 8g then; pressure reducing and steaming solvent, column chromatography for separation obtain product 0.51 gram, productive rate 73%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.15 (s, 9H), 3.47 (dd, J=13.8,10.7Hz, 1H), 3.54 (dd, J=13.8,4.0Hz, 1H), 4.62 (dd, J=10.7,4.1Hz, 1H), 7.14 (t, J=14.7Hz, 3H), 7.21 (tt, J=7.1,1.4Hz, 1H), 7.28 (t, J=15.5Hz, 7H), 7.35-7.39 (m, 3H).
Example 4:N-phenyl-N-(trimethyl silicon based)-1-(2-chloro-phenyl-)-2-phenyl-ethyl amine
(1) with embodiment 1 step (1)
(2) α-(2-chloro-phenyl-)-N-phenyl nitrone is synthetic
Under protection of nitrogen gas; with N-Phenylhydroxylamine (1.09g; 10.0mmol) (1.69g 12mmol) is dissolved in the dehydrated alcohol (20ml), is heated to about 65 ℃ with o-chlorobenzaldehyde; reacted 4 hours; the pressure reducing and steaming solvent gets crude product, with crude product ethyl acetate and sherwood oil recrystallization; can obtain product 1.95 grams, productive rate 84%.Fusing point: 83-84 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 7.35-7.58 (m, 6H), 7.70-7.82 (m, 2H), 8.43 (s, 1H), 9.53 (dd, J=7.6,2.0Hz, 1H).
(3) N-phenyl-N-(trimethyl silicon based)-1-(2-chloro-phenyl-)-2-phenyl-ethyl amine is synthetic
To be dissolved in α-(2-chloro-phenyl-)-N-phenyl nitrone (0.41g of tetrahydrofuran (THF) (10ml); 1.77mmol); slowly be added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol); to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the above-mentioned flask; under nitrogen protection, be heated to about 30 ℃; reacted 5 hours; the saturated ammonium chloride solution that adds 15ml carries out cancellation; with the ethyl acetate extraction of 50ml, use the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent; column chromatography for separation obtains product 0.59 gram, productive rate 84%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.15 (s, 9H), 3.55 (dd, J=14.6,3.8Hz, 1H), 3.77 (dd, J=14.3,11.4Hz, 1H), 5.62 (dd, J=11.2,3.7Hz, 1H), 7.36-7.40 (m, 2H), 7.44 (t, J=20.1Hz, 2H), 7.50 (dd, J=7.7,1.7Hz, 1H), 7.56 (dd, J=7.5,1.4Hz, 1H), 7.60-7.63 (m, 3H), 7.65 (dd, J=7.2,2.4Hz, 2H), 7.70 (dd, J=8.8,1.6Hz, 2H), 8.00 (dd, J=7.9,1.7Hz, 1H).
Synthesizing of example 5:N-phenyl-N-(trimethyl silicon based)-1-(3,4, the 5-trimethoxyphenyl)-2-phenyl-ethyl amine
(1) with embodiment 1 step (1)
(2) α-(3,4, the 5-trimethoxyphenyl)-N-phenyl nitrone is synthetic
Under protection of nitrogen gas, (1.09g is 10.0mmol) with 3 with N-Phenylhydroxylamine; 4; (2.35g 12mmol) is dissolved in the dehydrated alcohol (20ml) the 5-TMB, is heated to about 65 ℃; reacted 4 hours; the pressure reducing and steaming solvent gets crude product, with crude product ethyl acetate and sherwood oil recrystallization; can obtain product 2.42 grams, productive rate 84%.Fusing point: 147-149 ℃.
Its reaction formula is as follows:
Spectroscopic data::
1HNMR (400MHz, CDCl
3), δ (ppm): 3.94 (s, 3H), 3.94 (s, 6H), 7.48-7.50 (m, 3H), 7.77 (d, J=1.5Hz, 1H), 7.79 (s, 3H), 7.88 (s, 1H).
(3) N-phenyl-N-(trimethyl silicon based)-1-(3,4, the 5-trimethoxyphenyl)-2-phenyl-ethyl amine is synthetic
To be dissolved in the α-(3 of tetrahydrofuran (THF) (10ml); 4; the 5-trimethoxyphenyl)-N-phenyl nitrone (0.50g; 1.77mmol); slowly splash in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol); to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the above-mentioned flask, under nitrogen protection, be heated to about 30 ℃, reacted 5 hours; the saturated ammonium chloride solution that adds 15ml carries out cancellation; with the ethyl acetate extraction of 50ml, use the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent; column chromatography for separation obtains product 0.68 gram, productive rate 82%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.15 (s, 9H), 3.39 (dd, J=13.7,10.5Hz, 1H), 3.50 (dd, J=13.9,3.9Hz, 1H), 3.86 (s, 6H), 3.95 (s, 3H), 4.60 (dd, J=10.3,3.9Hz, 1H), 6.59 (s, 2H), 7.18 (td, J=15.6,7.5Hz, 4H), 7.29 (dd, J=8.4,7.3Hz, 4H), 7.37 (t, J=15.6Hz, 2H).
Synthesizing of example 6:N-phenyl-N-(trimethyl silicon based)-1-(2,4 dichloro benzene base)-2-phenyl-ethyl amine
(1) with embodiment 1 step (1)
(2) α-(2,4 dichloro benzene base)-N-phenyl nitrone is synthetic
Under protection of nitrogen gas; (1.09g is 10.0mmol) with α-2,4 dichloro benzene formaldehyde (0.21g with N-Phenylhydroxylamine; 12mmol) be dissolved in the dehydrated alcohol (20ml); be heated to 65 ℃, reacted the pressure reducing and steaming solvent 4 hours; get crude product; crude product with ethyl acetate and sherwood oil recrystallization, can be obtained product 2.2 grams, productive rate 83%.Fusing point: 90-92 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 7.39 (dd, J=8.7,2.1Hz, 1H), 7.47-7.51 (m, 4H), 7.78 (dd, J=7.6,3.8Hz, 2H), 8.37 (s, 1H), 9.52 (dd, J=8.74Hz, 1H).
(3) N-phenyl-N-(trimethyl silicon based)-1-(2,4 dichloro benzene base)-2-phenyl-ethyl amine is synthetic
To be dissolved in the α-(2 of tetrahydrofuran (THF) (10mmol), the 4-dichlorophenyl)-N-phenyl nitrone (0.47g, 1.77mmol), slowly be added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol), to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then, 2.67mmol) be added drop-wise in the flask, under nitrogen protection, be heated to about 30 ℃, reacted 5 hours; The saturated ammonium chloride solution that adds 15ml carries out cancellation, with the ethyl acetate extraction of 50ml, uses the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent, and column chromatography for separation obtains product 0.59 gram, productive rate 80%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.15 (s, 9H), 3.58 (dd, J=14.3,3.6Hz, 1H), and 3.61-3.68 (m, 1H), 5.52 (ddd, J=11.22,4.1,1.8Hz, 1H), 7.25 (d, J=7.19Hz, 2H), 7.32-7.37 (m, 2H), and 7.39-7.43 (m, 2H), 7.56-7.62 (m, 6H), 7.88 (dd, J=10.0Hz, 1H).
Synthesizing of example 7:N-phenyl-N-(trimethyl silicon based)-1-furyl-2-phenyl-ethyl amine:
(1) with embodiment 1 step (1)
(2) 2-furans-N-phenyl nitrone is synthetic
Under protection of nitrogen gas; with N-Phenylhydroxylamine (1.09g; 10.0mmol) and 2 furan carboxyaldehyde (1.15g; 12mmo1) be dissolved in the dehydrated alcohol (20ml), be heated to 65 ℃, reacted 4 hours; get crude product; crude product with ethyl acetate and sherwood oil recrystallization, can be obtained product 1.5 grams, productive rate 80%.Fusing point: 86-87 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 6.65 (d, J=1.5Hz, 1H), 7.43-7.52 (m, 3H), 7.59 (d, J=1.0, Hz, 1H), 7.75-7.84 (m, 2H), 8.02 (s, 1H), 8.2 (s, 1H).
(3) N-phenyl-N-(trimethyl silicon based)-1-furyl-2-phenyl-ethyl amine is synthetic
To be dissolved in the 2-furans-N-phenyl nitrone (0.33g of tetrahydrofuran (THF) (10ml); 1.77mmol); slowly be added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol); to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the flask; under nitrogen protection about direct heating to 30 ℃; reacted 5 hours; the saturated ammonium chloride solution that adds 15ml carries out cancellation; with the ethyl acetate extraction of 50ml, use the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent; column chromatography for separation obtains product 0.45 gram, productive rate 73%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.13 (s, 9H), 3.37 (d, J=7.2Hz, 2H), 4.70 (m, 1H), 6.26-6.37 (m, 2H), 7.12-7.23 (m, 4H), 7.25-7.30 (m, 4H), 7.37-7.40 (m, 2H), 7.45-7.47 (m, 1H).
Synthesizing of example 8:N-phenyl-N-(trimethyl silicon based)-1-thienyl-2-phenyl-ethyl amine
(1) with embodiment 1 step (1)
(2) 2-thiophene-N-phenyl nitrone is synthetic
Under protection of nitrogen gas, with N-Phenylhydroxylamine (1.09g, 10.0mmol) (1.35g 12mmol) is dissolved in the dehydrated alcohol (20ml), is heated to about 65 ℃, react 4 hours, and the pressure reducing and steaming solvent must crude product with 2 thiophene carboxaldehyde; Crude product with ethyl acetate and sherwood oil recrystallization, can be obtained product 1.7 grams, productive rate 84%.Fusing point: 87-88 ℃.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 7.22-7.26 (m, 1H), 746-7.52 (m, 3H), 7.58 (dd, J=5.1,0.6Hz, 1H), 7.62 (d, J=3.9Hz, 1H), 7.83-7.86 (m, 2H), 8.50 (s, 1H).
(3) N-phenyl-N-(trimethyl silicon based)-1-thienyl-2-phenyl-ethyl amine is synthetic
To be dissolved in the 2-thiophene-N-phenyl nitrone (0.36g of tetrahydrofuran (THF) (10ml); 1.77mmol); slowly be added drop-wise in the round-bottomed flask (100ml) that fills organic zinc reagent (2.67mmol); to be dissolved in the trimethylchlorosilane (0.29g of tetrahydrofuran (THF) (20ml) then; 2.67mmol) be added drop-wise in the above-mentioned reaction solution; under nitrogen protection, be heated to about 30 ℃; reacted 5 hours; the saturated ammonium chloride solution that adds 15ml carries out cancellation; with the ethyl acetate extraction of 50ml, use the anhydrous magnesium sulfate drying of 8g then, the pressure reducing and steaming solvent; column chromatography for separation obtains product 0.48 gram, productive rate 73%.
The isolating stationary phase of column chromatography is a silica gel, and moving phase is the mixed solution of sherwood oil or sherwood oil and ethyl acetate composition.
Its reaction formula is as follows:
Spectroscopic data:
1HNMR (400MHz, CDCl
3), δ (ppm): 0.15 (s, 9H), 3.52 (dd, J=13.7,3.7Hz, 1H), 4.84 (dd, J=10.5,3.8Hz, 1H), 6.65 (s, 1H), 6.80 (dd, J=4.0,3.5Hz, 1H), 7.05 (t, J=14.4Hz, 1H), 7.13 (t, J=13.1Hz, 3H), 7.16-7.21 (m, 5H), 7.27 (t, J=15.7Hz, 3H).
Claims (2)
1.N, the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-, its structure is shown below:
R
1Be alkyl, aromatic base or heterogeneous ring compound;
R
2Be alkyl, aromatic base or heterogeneous ring compound;
R
4Be alkyl, aromatic base.
2. N according to claim 1, the preparation method of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-comprises following processing step:
1. the preparation of N-substituted hydroxylamine: in ammonium chloride solution, with nitro-hydrocarbon and zinc powder mol ratio, in 60～75 ℃ of reactions 1～8 hour down with 1: 1～1: 5, filter, washing adds sodium-chlor and makes the solution supersaturated solution, the thick product of N-Phenylhydroxylamine is separated out in the ice-water bath cooling.Crude product obtains N-substituted hydroxylamine compound with methylene dichloride and sherwood oil recrystallization;
Described nitro-hydrocarbon is nitroparaffins or nitro-aromatic;
The concentration of described ammonium chloride solution is 0.3～0.5g/ml;
2. the preparation of nitrone: in organic solvent, with N-substituted hydroxylamine compound and aldehyde compound mixed in molar ratio, in 0～80 ℃ of reaction 3～9 hours down with 1: 1～2: 1, the pressure reducing and steaming solvent, obtain crude product, with crude product ethyl acetate and sherwood oil recrystallization, obtain nitrone again;
Described aldehyde compound comprises aromatic aldehyde and alkanoic;
Described organic solvent is protic solvent or non-non-protonic solvent;
3. N, the preparation of the two replacement-O-trialkyl silicon-based hydroxylamine compounds of N-: under nitrogen protection, in non-proton organic solvent, with nitrone, organometallic reagent, trialkyl halosilanes mixed in molar ratio, in 0～60 ℃ of reaction 1～10 hour down with 1: 1: 1～1: 2: 2, add saturated ammonium chloride solution and carry out cancellation, use ethyl acetate extraction, use anhydrous magnesium sulfate drying then, filter, the pressure reducing and steaming solvent, column chromatography for separation obtains product;
Described organometallic reagent is organolithium, organic-magnesium, organic zinc, organic copper or organosilicon reagent;
Alkyl in the described trialkyl halosilanes is aliphatic hydrocarbon or aromatic hydrocarbon; Halogen is the arbitrary halogen in chlorine, bromine, iodine, the fluorine in the trialkyl halosilanes.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103086974A (en) * | 2013-02-01 | 2013-05-08 | 湖南海利化工股份有限公司 | Preparation method for N-[2-[[1-(4-chlorphenyl)pyrazole-2-base]methoxy] phenyl] hydroxylamine |
| CN103172868A (en) * | 2011-12-16 | 2013-06-26 | 赢创工业集团股份有限公司 | Siloxane nitrones and their application |
-
2010
- 2010-06-19 CN CN201010208376A patent/CN101863915A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103172868A (en) * | 2011-12-16 | 2013-06-26 | 赢创工业集团股份有限公司 | Siloxane nitrones and their application |
| CN103172868B (en) * | 2011-12-16 | 2015-05-06 | 赢创工业集团股份有限公司 | Siloxane nitrones and their application |
| CN103086974A (en) * | 2013-02-01 | 2013-05-08 | 湖南海利化工股份有限公司 | Preparation method for N-[2-[[1-(4-chlorphenyl)pyrazole-2-base]methoxy] phenyl] hydroxylamine |
| CN103086974B (en) * | 2013-02-01 | 2014-10-29 | 湖南海利化工股份有限公司 | Preparation method for N-[2-[[1-(4-chlorphenyl)pyrazole-2-base]methoxy] phenyl] hydroxylamine |
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