CN102060754B - Method for preparing polysubstituted tetrahydropyridine - Google Patents
Method for preparing polysubstituted tetrahydropyridine Download PDFInfo
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- CN102060754B CN102060754B CN2010105629204A CN201010562920A CN102060754B CN 102060754 B CN102060754 B CN 102060754B CN 2010105629204 A CN2010105629204 A CN 2010105629204A CN 201010562920 A CN201010562920 A CN 201010562920A CN 102060754 B CN102060754 B CN 102060754B
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- tetrahydropyridine
- polysubstituted
- hydrochloric acid
- hydrogen
- aldehyde
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- YYTSRURMYPFAIZ-UHFFFAOYSA-N CCOC(C(C(c1ccccc1)N(C(C1)c2ccccc2)c(cc2)ccc2Cl)=C1Nc(cc1)ccc1Cl)=O Chemical compound CCOC(C(C(c1ccccc1)N(C(C1)c2ccccc2)c(cc2)ccc2Cl)=C1Nc(cc1)ccc1Cl)=O YYTSRURMYPFAIZ-UHFFFAOYSA-N 0.000 description 1
- FRDSZCWEQWUCBI-UHFFFAOYSA-N Cc1ccc(C(CC(Nc2ccc(C)cc2)=C(C2c3ccc(C)cc3)C(OCC=C)=O)N2c2ccc(C)cc2)cc1 Chemical compound Cc1ccc(C(CC(Nc2ccc(C)cc2)=C(C2c3ccc(C)cc3)C(OCC=C)=O)N2c2ccc(C)cc2)cc1 FRDSZCWEQWUCBI-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Nc1ccccc1 Chemical compound Nc1ccccc1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N O=Cc1ccccc1 Chemical compound O=Cc1ccccc1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a new method for synthesizing polysubstituted tetrahydropyridine. In the method, a series of polysubstituted tetrahydropyridines are prepared by using low-cost and nontoxic hydrochloric acid as a catalyst and aromatic aldehyde, active methylene substances and aromatic amine as raw materials and by a one-pot process, the polysubstituted tetrahydropyridine yield (which is over 80 percent) is high; and the product quality (the purity is over 99 percent) is high; other organic solvents which are adverse to environment are not used in a reaction, so the pollution of the solvents and the catalyst on the environment is reduced, and the environmentally-friendly chemical synthesis is realized; and the polysubstituted tetrahydropyridine is synthesized by a multicomponent one-pot process, so the preparation method is economic in steps, simple in operation and low in cost, has mild reaction condition, is easy and convenient to operate, and is favorable for industrial production.
Description
Technical field
The invention belongs to organic chemistry filed, relate to a kind of preparation method of polysubstituted tetrahydropyridine, relate in particular to a kind of utilization and utilize aromatic aldehyde, active methylene base class material, aromatic amine to prepare the method for polysubstituted tetrahydropyridine.
Background technology
Polysubstituted tetrahydropyridine is one type of important organic cpds, in the molecule of many natural products and biologically active, all has its structural framework, gets more and more people's extensive concerning as the structural unit of many bioactive compoundss.Polysubstituted tetrahydropyridine, its chemical structural formula is following:
Wherein, R
1=H, 4-CH
3, 2-NO
2, 3-NO
2, 4-NO
2, 2-Cl, 3-Cl, 4-Cl, 2,4-DiCl, 2-OCH
3, 4-OCH
3, 3,4-DiOCH
3R
2=CH
2CH
3, CH
2CH=CH
2R
3=H, 4-CH
3, 4-Cl, 4-Br.
At present, the report of relevant polysubstituted tetrahydropyridine compound method is a lot.Wherein following several method is used comparatively extensive: first method is the cyclisation method, and promptly the C-N key becomes ring or through forming C-C key Cheng Huan, this method is to form one of the most frequently used method of piperidine ring through forming.As through intramolecular nucleophilic substitution reaction (Tetrahedron 2001,57,6955; Chirality 2000,12,342), promote cyclisation (Chem.Lett.1997,221 through organic palladium, silver, mercury, tin compound; Asymmetry 1995,6, and 1077; Heterocycles-cycles2000,53,115), the nucleophilic addition(Adn) (J.Org.Chem.1999,64,1160) of carbanion, the promoted intramolecularly addition of Lewis acid (TetrahedronAsymmetry 1997,8,3387).Second method is the cycloaddition method, and promptly intramolecular Didls-Alder reaction (Tetrahedron 1998,54, and 1317; J.Org.Chem.Soc.2000,122,4583; J.Org.Chem.2001,66.3338), intermolecular Didls-A1der reacts (J.Org.Chem.1996,61,4594; J.Org.Chem.1992,58,2075), intramolecular imines Didls-Alder reacts (Org.Let.2000,2,4007).
In these methods, some method has been used organic solvent, and some method also need be used conditions such as heavy metal catalyst, low temperature; In addition, some method then side reaction is many, and productive rate is low, can not be applied to reality, does not also meet the requirement of Green Chemistry.
Summary of the invention
Order of the present invention is in order to overcome the problem of existence, and providing a kind of is catalyzer with the concentrated hydrochloric acid, utilizes aromatic aldehyde, active methylene base class material, aromatic amine to be raw material, adopts one kettle way to prepare the method for polysubstituted tetrahydropyridine.
Its concrete technological process is following: be to be catalyzer with the concentrated hydrochloric acid, make solvent with ethanol, make aromatic aldehyde, active methylene base class material, aromatic amine with 1: 1: 1～1: 2: 1 mol ratio, 55～60 ℃ of following stirring reactions 19～23 hours; After reaction finishes, use ethyl acetate extraction, separatory boils off behind the solvent with ethanol-DMF recrystallization, must polysubstituted tetrahydropyridine.
Said aromatic aldehyde is a phenyl aldehyde, the 4-tolyl aldehyde; 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde; 2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2,4 dichloro benzene formaldehyde, 2-methoxybenzaldehyde, 4-methoxybenzaldehyde, 3,4-dimethoxy benzaldehyde.
Said active methylene base class material is ethyl ethylacetoacetate or ethyl allylacetylacetate.
Said aromatic amine is aniline, 4-monomethylaniline 4-chloroaniline or 4-bromaniline.
The concentration of said concentrated hydrochloric acid is 10～12mol/L, and the molar weight of concentrated hydrochloric acid is 5～10% of an aromatic aldehyde.
Its building-up process is shown below:
Wherein, R
1=H, 4-CH
3, 2-NO
2, 3-NO
2, 4-NO
2, 2-Cl, 3-Cl, 4-Cl, 2,4-DiCl, 2-OCH
3, 4-OCH
3, 3,4-DiOCH
3R
2=CH
2CH
3, CH
2CH=CH
2R
3=H, 4-CH
3, 4-Cl, 4-Br.
The present invention compared with prior art has the following advantages:
1, make solvent with green ethanol, adopting the hydrochloric acid of non-toxic inexpensive is catalyzer, utilizes aromatic aldehyde, active methylene base class material, aromatic amine to be raw material, adopts one kettle way to obtain a series of single products: polysubstituted tetrahydropyridine, and productive rate is high: can reach more than 80%; Quality product is high: purity is more than 99%.
2, do not use other to the disadvantageous organic solvent of environment in the reaction, reduced the pollution of solvent and catalyzer, realized environment amenable chemosynthesis environment.
3, adopt the polycomponent one kettle way synthetic, step economy, simple to operate, be applicable to multiple aromatic aldehyde and aromatic amine.
4, of the present invention being reflected under 55～60 ℃ carried out, and reaction conditions is gentle, and is easy to operation, is beneficial to suitability for industrialized production.
Embodiment
Embodiment 1,1-(4-chloro-phenyl-)-4-(4-chloroanilino)-2,6-phenylbenzene-1,2,5, the preparation of 6-tetrahydropyridine-3-ethyl-carbonate
In the reaction flask that adds ethanol (2mL) (50mL round-bottomed flask), and the adding phenyl aldehyde (0.212g, 2mmol); Methyl aceto acetate (0.260g, 2mmol), 4-chloroaniline (0.256g; 2mmol), dripping concentration again is the concentrated hydrochloric acid 0.02mL of 12mol/L, and controlled temperature stirred 23 hours down at 60 ℃; Reaction finishes the back and in reaction flask, adds ETHYLE ACETATE (15mL) and water (5mL), stirs and leaves standstill separatory after 10 minutes; Tell organic phase, water merges all organic phases after using ETHYLE ACETATE (10mL) to extract 3 times again; Carry out recrystallization (3 times) with ethanol-DMF after boiling off solvent, at last pure article 1-(4-chloro-phenyl-)-4-(4-chloroanilino)-2,6-phenylbenzene-1; 2,5,6-tetrahydropyridine-3-ethyl-carbonate.Productive rate is: 80%.
This product is a white solid.
The ir data of product of the present invention is following:
IR(υ/cm
-1)：3446，3244，2974，2857，1646，1603，1495，1320，1255，1071，941，803，729，697。
The nuclear magnetic resonance data of product of the present invention is following:
1H?NMR(400MHz，CDCl
3)：δ＝10.25(s，1H)，7.32-6.99(m，14H)，6.43(t，J＝9.6Hz，3H)，6.18(d，J＝8.0Hz，2H)，5.12(s，1H)，4.50-4.32(m，2H)，2.87-2.68(m，2H)，1.48(t，J＝8.0Hz，3H)；
13C?NMR(100MHz，CDCl
3)：δ＝168.10，155.32，145.48，143.21，142.23，136.38，131.31，128.93，128.70，128.70，128.30，127.38，126.96，126.47，126.47，126.24，121.20，113.98，98.68，59.85，58.25，55.23，33.42，14.73。
1 H at proton nmr spectra chemical shift 10.25 places is a H on the NH on the anilino; 7.32-6.99 be 14 hydrogen on the phenyl ring; 6.43 3 H that locate and 2 H at 6.18 places are four hydrogen and 1 hydrogen on methyne on the phenyl ring; 5.12 1 H that locates is 1 hydrogen on the another one methyne; 4.50-4.32 2 H are 2 hydrogen on the methylene radical on the pyridine ring, 2 H on the methylene radical that 2 H are with ester group links to each other at 2.87-2.68 place, three H at 1.48 places are 3 H of methyl on the ester group end.24 types of carbon atoms of this product structure all occur in the carbon spectrum.
The results of elemental analyses of this product is following:
Anal.Calcd.for?C
32H
28Cl
2N
2O
2：C，70.72；H，5.19；N，5.15；Found：C，71.12；H，5.22；N，5.18％。
The structural formula of this product is following:
Embodiment 2,1-phenyl-4-anilino-2,6-two (3, the 4-Dimethoxyphenyl)-1,2,5, the preparation of 6-tetrahydropyridine-3-carbonic acid allyl ester
In the reaction flask that adds ethanol (2mL) (50mL round-bottomed flask), add 3,4-dimethoxy benzaldehyde (0.332g; 2mmol), and acetoacetic acid allyl ester (0.284g, 2mmol); Aniline (0.186g; 2mmol), dripping concentration again is the concentrated hydrochloric acid 0.02mL of 12mol/L, and controlled temperature stirred 19 hours down at 60 ℃; Reaction finishes the back and in reaction flask, adds ETHYLE ACETATE (15mL) and water (5mL), stirs and leaves standstill after 10 minutes, and separatory is told organic phase; Water merges all organic phases after using ETHYLE ACETATE (10mL) extraction 3 times again, carries out recrystallization (3 times) with ethanol-DMF after boiling off solvent; At last pure article 1-phenyl-4-anilino-2,6-two (3, the 4-Dimethoxyphenyl)-1; 2,5,6-tetrahydropyridine-3-carbonic acid allyl ester.Productive rate is: 87%.
This product is a white solid.
The ir data of product of the present invention is following:
IR(υ/cm
-1)：3429，3251，2933，2835，1659，1592，1502，1132，1028，765。
The nuclear magnetic resonance data of product of the present invention is following:
1H?NMR(400MHz，CDCl
3)：δ＝10.31(s，1H)，7.16-7.06(m，4H)，6.99(s，1H)，6.78-6.39(m，12H)，6.16-6.07(m，1H)，5.49-5.30(m，2H)，5.07(s，1H)，4.92-4.73(m，2H)，3.87(s，3H)，3.84(s，3H)，3.80(s，3H)，3.72(s，3H)，2.98-2.77(m，2H)；
13C?NMR(100MHz，CDCl
3)：δ＝167.65，157.04，149.03，148.88，147.94，147.44，146.94，137.77，136.24，134.96，133.06，128.81，128.78，125.94，125.83，118.56，118.44，117.96，116.21，113.01，111.13，110.40，110.04，109.15，97.40，64.37，57.75，55.91，55.79，55.72，55.68，54.93，33.74。
1 H at proton nmr spectra chemical shift 10.31 places is a H on the NH on the anilino; 7.16-7.06 be 4 hydrogen on the phenyl ring, 1 H at 6.99 places is 1 hydrogen on the methyne, the 6.78-6.39 place is other 12 hydrogen on the phenyl ring; 6.16-6.07 1 H that locates is 1 hydrogen on the another one methyne; 5.49-5.30 2 H are 2 H of methylene radical on the pyridine ring, 1 H at 5.07 places is 1 H on two keys, 4.92-4.73 is 2 terminal H of two keys; 3.87,3.84,3.80,3.72 places altogether 12 H be 12 H on four methoxyl groups on the phenyl ring, 2 H on the methylene radical that 2 H are with ester group links to each other at 2.98-2.77 place.33 types of carbon atoms of this product structure all occur in the carbon spectrum.
The results of elemental analyses of this product is following:
Anal.Calcd.for?C
37H
38N
2O
6：C，73.25；H，6.31；N，4.62.Found：C，73.65；H，6.34；N，4.65％。
The structural formula of this product is following:
Embodiment 3,1-(4-chloro-phenyl-)-4-(4-chloroanilino)-2,6-two (2-p-methoxy-phenyl)-1,2,5, the preparation of 6-tetrahydropyridine-3-allyl carbonate
In the reaction flask that adds ethanol (2mL) (50mL round-bottomed flask), and adding 2-methoxybenzaldehyde (0.272g, 2mmol); Acetoacetic acid allyl ester (0.284g; 2mmol), and the 4-chloroaniline (0.256g, 2mmol); Dripping concentration again is the concentrated hydrochloric acid 0.02mL of 12mol/L, and controlled temperature stirred 19 hours down at 60 ℃; Reaction finishes the back and in reaction flask, adds ETHYLE ACETATE (15mL) and water (5mL), stirs and leaves standstill separatory after 10 minutes; Tell organic phase, water merges all organic phases after using ETHYLE ACETATE (10mL) to extract 3 times again; Carry out recrystallization (3 times) with ethanol-DMF after boiling off solvent, at last pure article 1-(4-chloro-phenyl-)-4-(4-chloroanilino)-2,6-two (2-p-methoxy-phenyl)-1; 2,5,6-tetrahydropyridine-3-allyl carbonate.Productive rate is: 80%.
This product is a white solid.
The ir data of product of the present invention is following:
IR(υ/cm
-1)：3448，3250，2935，2836，1662，1594，1491，1462，1374，1241，1096，1029，752。
The nuclear magnetic resonance data of product of the present invention is following:
1H?NMR(400MHz，CDCl
3)：δ＝9.72(s，1H)，7.30-6.82(m，12H)，6.46(s，1H)，6.38-6.19(m，4H)，6.17-6.10(m，1H)，5.51-5.42(m，2H)，5.34-5.31(m，1H)，4.93-4.78(m，2H)，3.84(s，3H)，3.70(s，3H)，2.98-2.84(m，2H)；
13C?NMR(100MHz，CDCl
3)：δ＝168.18，157.36，156.14，156.00，154.49，145.33，137.08，133.24，130.70，129.70，129.41，128.87，128.61，128.37，127.98，127.83，127.11，120.77，120.69，119.62，117.09，113.70，111.11，109.91，98.33，64.31，55.19，54.94，53.26，53.22，29.16。
1 H at proton nmr spectra chemical shift 9.72 places is a H on the NH on the anilino; 7.30-6.82 be 12 hydrogen on the phenyl ring, 1 H at 6.46 places is 1 hydrogen on the methyne, 4 H at 6.38-6.19 place are 4 other on phenyl ring H; 6.17-6.10 locate to be 1 H on the another one methyne; 5.51-5.42 2 H that locate are 2 H of methylene radical on the pyridine ring, the 5.34-5.31 place is a H on two keys, and the 4.93-4.78 place is 2 H on two keys; 3.84,3.70 places are 6 H on two methoxyl groups on the phenyl ring, 2 hydrogen on the methylene radical that 2.98-2.84 is with ester group links to each other.31 types of carbon atoms of this product structure all occur in the carbon spectrum.
The results of elemental analyses of this product is following:
Anal.Calcd.for?C
35H
32Cl
2N
2O
4：C，68.29；H，5.24；N，4.55.Found：C，68.69；H，5.28；N，4.59％。
The structural formula of this product is following:
Embodiment 4,1-(4-bromophenyl)-4-(4-bromobenzene amido)-2,6-two (4-p-methoxy-phenyl)-1,2,5, the preparation of 6-tetrahydropyridine-3-ethyl-carbonate
In the reaction flask that adds ethanol (2mL) (50mL round-bottomed flask), and adding 4-methoxybenzaldehyde (0.0.272g, 2mmol); Methyl aceto acetate (0.260g; 2mmol), and the 4-bromaniline (0.344g, 2mmol); Dripping concentration again is the concentrated hydrochloric acid 0.02mL of 12mol/L, and controlled temperature stirred 23 hours down at 60 ℃; Reaction finishes the back and in reaction flask, adds ETHYLE ACETATE (15mL) and water (5mL), stirs and leaves standstill separatory after 10 minutes; Tell organic phase, water merges all organic phases after using ETHYLE ACETATE (10mL) to extract 3 times again; Carry out recrystallization (3 times) with ethanol-DMF after boiling off solvent, at last pure article 1-(4-bromophenyl)-4-(4-bromobenzene amido)-2,6-two (4-p-methoxy-phenyl)-1; 2,5,6-tetrahydropyridine-3-ethyl-carbonate.Productive rate is: 88%.
This product is a white solid.
The ir data of product of the present invention is following:
IR(υ/cm
-1)：3445，3245，2976，2835，1648，1605，1504，1319，1250，1178，1068，1034，809。
The nuclear magnetic resonance data of product of the present invention is following:
1H?NMR(400MHz，CDCl
3)：δ＝10.24(s，1H)，7.26-7.03(m，8H)，6.40-6.38(m，2H)，6.28(s，1H)，6.21-6.18(m，6H)，5.02(s，1H)，4.47-4.30(m，2H)，3.80(s，3H)，3.78(s，3H)，2.86-2.67(m，2H)，1.46(t，J＝6.8Hz，3H)；
13C?NMR(100MHz，CDCl
3)：δ＝168.12，158.90，158.22，155.28，145.95，137.04，135.06，133.94，131.97，131.53，127.53，127.34，127.13，118.96，114.62，114.12，113.69，108.31，99.02，60.82，59.87，57.54，55.26，54.65，33.56，14.76。
1 H at proton nmr spectra chemical shift 10.24 places is a H on the NH on the anilino; 7.26-7.03 be 8 hydrogen on the phenyl ring; 6.40-6.38 26 H with the 6.21-6.18 place are 8 other on phenyl ring H, 6.28 places are 1 hydrogen on the methyne, 1 H at 5.02 places is 1 hydrogen on the another one methyne; 4.47-4.30 2 H are 2 H of methylene radical on the pyridine ring; 3.80,6 H at 3.78 places are 6 hydrogen on two methoxyl groups on the phenyl ring, 2 H on the methylene radical that 2 H are with ester group links to each other at 2.86-2.67 place, three H at 1.46 places are 3 H of methyl on the ester group end.26 types of carbon atoms of this product structure all occur in the carbon spectrum.
The results of elemental analyses of this product is following:
Anal.Calcd.for?C
34H
32Br
2N
2O
4：C，58.97；H，4.66；N，4.05.Found：C，59.38；H，4.70；N，4.10％。
The structural formula of this product is following:
Embodiment 5,1-(4-aminomethyl phenyl)-4-(4-toluidine)-2,6-two (4-aminomethyl phenyl)-1,2,5, the preparation of 6-tetrahydropyridine-3-carbonic acid allyl ester
In the reaction flask that adds ethanol (2mL) (50mL round-bottomed flask), and adding 4-tolyl aldehyde (0.280g, 2mmol); Acetoacetic acid allyl ester (0.284g; 2mmol), and the 4-monomethylaniline (0.214g, 2mmol); Dripping concentration again is the concentrated hydrochloric acid 0.02mL of 12mol/L, and controlled temperature stirred 22 hours down at 60 ℃; Reaction finishes the back and in reaction flask, adds ETHYLE ACETATE (15mL) and water (5mL), stirs and leaves standstill separatory after 10 minutes; Tell organic phase, water merges all organic phases after using ETHYLE ACETATE (10mL) to extract 3 times again; Carry out recrystallization (3 times) with ethanol-DMF after boiling off solvent, at last pure article 1-(4-aminomethyl phenyl)-4-(4-toluidine)-2,6-two (4-aminomethyl phenyl)-1; 2,5, the preparation of 6-tetrahydropyridine-3-carbonic acid allyl ester.Productive rate is: 81%.
This product is a white solid.
The ir data of product of the present invention is following:
IR?(υ/cm
-1)：3448，3239，3024，2868，1642，1592，1323，1256，1177，800，492。
The nuclear magnetic resonance data of product of the present invention is following:
1H?NMR(400MHz，CDCl
3)：δ＝10.19(s，1H)，7.26-6.88(m，12H)，6.44-6.17(m，5H)，6.15-6.06(m，2H)，5.48-5.29(m，1H)，4.88(s，1H)，4.85-4.79(m，2H)，2.85-2.72(m，2H)，2.33(s，3H)，2.26(s，3H)，2.23(s，3H)，2.15(s，3H)；
13C?NMR(100MHz，CDCl
3)：δ＝167.79，156.97，144.90，141.28，139.85，136.47，135.64，135.51，135.19，133.18，129.39，129.35，129.20，128.87，126.58，126.33，125.94，124.84，117.44，112.80，97.39，64.21，57.83，54.91，33.61，21.09，20.99，20.86，20.11。
1 H at proton nmr spectra chemical shift 10.19 places is a H on the NH on the anilino; 7.26-6.88 be 12 hydrogen on the phenyl ring; 6.44-6.17 5 H that locate are four hydrogen and 1 hydrogen on methyne on the phenyl ring, 2 H at 6.15-6.06 place are 2 H of methylene radical on the pyridine ring, and a H at 5.48-5.29 place is 1 hydrogen on the another one methyne; 4.88 1 H that locates is a H on two keys; 4.85-4.79 locate 2 H being that two keys are terminal, 2 hydrogen on the methylene radical that the 2.85-2.72 place is with ester group links to each other, 12 H at 2.33,2.26,2.23 and 2.15 places are 12 H on four methyl on the phenyl ring.29 types of carbon atoms of this product structure all occur in the carbon spectrum.
The results of elemental analyses of this product is following:
Anal.Calcd.for?C
37H
38N
2O
2：C，81.88；H，7.06；N，5.16.Found：C，82.27；H，7.11；N，5.18％。
The structural formula of this product is following:
Claims (2)
1. the preparation method of a polysubstituted tetrahydropyridine was to be catalyzer with the concentrated hydrochloric acid, makes solvent with ethanol, makes aromatic aldehyde, active methylene base class material, aromatic amine with 1: 1: 1～1: 2: 1 mol ratio, 55～60 ℃ of following stirring reactions 19～23 hours; After reaction finishes, use ethyl acetate extraction, separatory boils off behind the solvent with ethanol-DMF recrystallization, must polysubstituted tetrahydropyridine;
Wherein:
Said aromatic aldehyde is phenyl aldehyde, 4-tolyl aldehyde, 2-nitrobenzaldehyde, 3-nitrobenzaldehyde, 4-nitrobenzaldehyde, 2-chlorobenzaldehyde, 3-chlorobenzaldehyde, 4-chlorobenzaldehyde, 2; 4-dichlorobenzaldehyde, 2-methoxybenzaldehyde, 4-methoxybenzaldehyde or 3, the 4-dimethoxy benzaldehyde;
Said active methylene base class material is methyl aceto acetate or acetoacetic acid allyl ester;
Said aromatic amine is aniline, 4-monomethylaniline, 4-chloroaniline or 4-bromaniline;
The structural formula of said polysubstituted tetrahydropyridine is:
R
1Be hydrogen, 4-methyl, 2-nitro, 3-nitro, 4-nitro, 2-chlorine, 3-chlorine, 4-chlorine, 2,4-dichloro, 2-methoxyl group, 4-methoxyl group or 3,4-dimethoxy;
R
2Be ethyl or allyl group;
R
3Be hydrogen, 4-methyl, 4-chlorine or 4-bromine.
2. the preparation method of polysubstituted tetrahydropyridine according to claim 1, it is characterized in that: the concentration of said concentrated hydrochloric acid is 10～12mol/L, the molar weight of concentrated hydrochloric acid is 5～10% of an aromatic aldehyde.
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| CN102690227A (en) * | 2012-05-30 | 2012-09-26 | 浙江大学 | Optical active tetrahydropyridine derivative and preparation method thereof |
| CN104926713A (en) * | 2015-05-24 | 2015-09-23 | 西北大学 | Synthetic method of polysubstitution 1,2,5,6-tetrahydropyridine compound |
| CN115073359A (en) * | 2022-05-26 | 2022-09-20 | 上海大学 | Preparation method of polysubstituted-1, 4,5, 6-tetrahydro-3-pyridinecarboxylic acid ethyl ester |
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| CN101723880A (en) * | 2009-11-20 | 2010-06-09 | 西北师范大学 | 1-phenyl-4-(anilino)-2,6-diaryl-1,2,5,6-tetrahydropyridine-3-etyl carbonate compound and synthesis method thereof |
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| CN101723880A (en) * | 2009-11-20 | 2010-06-09 | 西北师范大学 | 1-phenyl-4-(anilino)-2,6-diaryl-1,2,5,6-tetrahydropyridine-3-etyl carbonate compound and synthesis method thereof |
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| Abu T. Khan et al.Effects of Substituents in the β-Position of 1,3-Dicarbonyl Compounds in Bromodimethylsulfonium Bromide-Catalyzed Multicomponent Reactions: A Facile Access to Functionalized Piperidines.《The Journal of Organic Chemistry》.2008,第73卷(第21期),8398-8402. * |
| AbuT.Khanetal.EffectsofSubstituentsintheβ-Positionof1 3-Dicarbonyl Compounds in Bromodimethylsulfonium Bromide-Catalyzed Multicomponent Reactions: A Facile Access to Functionalized Piperidines.《The Journal of Organic Chemistry》.2008 |
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