CN110204456B - Polysubstituted naphthalene derivative and synthesis method thereof - Google Patents
Polysubstituted naphthalene derivative and synthesis method thereof Download PDFInfo
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Abstract
The invention relates to a polysubstituted naphthalene derivative and a synthesis method thereof, wherein the compound has the structure as follows:
the invention relates to a series cyclization reaction of 2,6-dimethyl phenyl isonitrile and propargyl alcohol acetate, which can synthesize polysubstituted naphthalene derivative with a more complex structure through the processes of rearrangement, intramolecular cyclization, ring opening, acyl migration, Friedel-crafts alkylation and the like. The reaction can be smoothly carried out without a transition metal catalyst, the reaction condition is mild, the experimental operation is simple and convenient, and the atom economy is good. The method provides a new synthetic route for the synthesis of the complex polysubstituted naphthalene, and has potential application value in organic synthesis.
Description
Technical Field
The invention relates to a polysubstituted naphthalene derivative and a synthesis method thereof.
Background
Substituted naphthalene derivatives are important skeletons of many compounds with biological activity (anti-inflammatory, antibacterial and anticancer), and substances with specific aromatic structures also have important application in many optical and electronic materials, and are also skeletons of many chiral ligands. Still other drugs with typical naphthalene ring structures play an important role in the control of microbial infections.
Naphthalene derivatives have important research and application values, and people are also working on researching simple methods for synthesizing naphthalene skeleton compounds. The methods for constructing polysubstituted benzene derivatives reported in the literature in recent years are mainly as follows:
tanaka et al, a method for synthesizing naphthalene derivatives by using a palladium catalyst. In the reactionBromoeneyne compound in the presence of palladium catalyst, 2.0 equivalents Cs2CO3Under the action of reflux in an ethanol solvent, intramolecular cyclization reaction is carried out to generate a naphthalene derivative (Scheme 1), see a reference: ohno, h.; yamamoto, m.; iuchi, m.; tanaka, T.Palladium-Catalyzed ligation of Bromoenys through Aromatic C-H Bond catalysis [ J].Angew.Chem.Int.Ed.2005,44(32):5103-5106。
Zhu et al used 2-alkylbenzaldehydes and alkynes via FeCl3A method for catalytically synthesizing naphthalene derivatives. The authors screened different Lewis acids, different solvents and finally found 5 mol% FeCl in DCE solvent at room temperature3When the catalyst is used, the target product with the yield of 98% is obtained after the 20mins reaction is finished. The method has the advantages of low catalyst price, wide substrate range, simple reaction conditions, high reaction yield and the like. (Scheme 2). See references: zhu, s.; xiao, y.; guo, z.; jiang, H.Iron-catalyzed benzanulationreaction of 2-alkyl benzazoles and alkyl leads to Naphthalene Derivatives [ J].Org.Lett.2013,15(4):898-901。
Xiang et al uses BF3·Et2A method for synthesizing naphthalene derivatives by catalyzing phenylacetaldehyde and phenylacetylene with O. Phenylacetaldehyde and phenylacetylene in BF3·Et2The target naphthalene derivative (Scheme 3) is obtained with the yield of 82% under the optimal conditions of O catalysis and heating in a DCE solvent at the temperature of 80 ℃ for about 15.0 h. See references: xiang, s.; hu, h; ma, j.; li, Y.; wang, b.; feng, C.; zhao, k.; hu, p.; (iii) Chen, X. Synthesis of naphthalene derivatives through inner permanent BF3·Et2O-catalyzed annulation reaction of arylacetaldehydes with arylalkynes[J].Sci.China Chem.2013,56(7):945-951。
Liu et al use Cu catalysts, coupled cyclization reactions of borate esters with propargyl alcohol esters to give polysubstituted 3-borane-1-naphthylamine, with regioselectivity and broad functional group compatibility. In addition, this is the first time that the cyano group, which normally provides a carbocyclic ring, is trapped to catalyze the formation of copper alkenyl species (Scheme 4). See references: xiong, m.; xie, x.; liu, y.org.lett.2017,19,3398.
In the methods for selectively constructing the polysubstituted naphthalene, the catalyst is expensive, the reaction time is long, the yield is low and the like. Therefore, the method for synthesizing the naphthalene derivative has important significance in finding a method which is easy to obtain raw materials, mild in reaction conditions and simple to operate.
Disclosure of Invention
One of the objects of the present invention is to provide a polysubstituted naphthalene derivative.
The invention also aims to provide a synthetic method of the compound.
To achieve the above object, the reaction equation of the present invention is:
according to the reaction mechanism, the invention adopts the following technical scheme:
a polysubstituted naphthalene derivative and its synthetic method, characterized by that the structure of this compound is:
wherein R is H, methyl, methoxyl and halogen element; xyl is 2, 6-dimethylphenyl.
A method for preparing the polysubstituted naphthalene derivative is characterized by comprising the following steps: dissolving 2, 6-dimethylphenyliisonitrile and propargyl alcohol acetate in 3 ml-5 ml of chlorobenzene according to the molar ratio of 3: 1-2: 1, stirring at 110-140 ℃, and monitoring the reaction by TLC; after the reaction is finished, evaporating the solvent under reduced pressure, and separating and purifying to obtain the polysubstituted naphthalene derivative; the structural formula of the propargyl alcohol acetate is as follows:
wherein R is H, methyl, methoxyl and halogen element; xyl is 2, 6-dimethylphenyl.
The invention provides a method for efficiently synthesizing naphthalene derivatives with 5 different functional groups, which has the advantages of mild reaction conditions, no need of any catalyst, simple and convenient operation and good atom economy. The invention has important application in many optical and electronic materials, is also a framework of many chiral ligands, and plays an important role in the control of microbial infection.
Drawings
FIG. 1 is a single crystal diagram of Compound 3 a.
FIGS. 2-11 show nuclear magnetic hydrogen and carbon spectra of compounds 3a-3e, respectively.
Detailed Description
The synthesis method of the present invention for constructing polysubstituted naphthalene derivatives is described in detail below with reference to the accompanying drawings, but the present invention is not limited to the following examples. Preferred embodiments of the present invention have been described in detail for the purpose of providing a thorough understanding of the present invention.
The first embodiment is as follows: adding 3mL of chlorobenzene as a solvent into a 25mL pressure-resistant sealed tube, adding two reactants of propargyl alcohol acetate (0.5mmol) and 2,6-dimethylphenyl isonitrile (1.5mmol) into the solvent, sealing the pressure-resistant tube, reacting at 140 ℃, and performing tracking detection by TLC until the reaction is finished. The reaction system was subjected to rotary evaporation under vacuum to give a concentrate, which was separated by column chromatography (eluent: PE: EA ═ 30:1) to give the target product 3a (183mg, 72% yield).
The structural formula of compound 3a is:
the molecular formula is as follows: c32H32N2O4
Chinese naming: 3- (acetyl (2, 6-dimethylphenyl) carbamoyl) -1- ((2, 6-dimethylphenyl) amino) -2-naphthoic acid ethyl ester
English naming:
Ethyl 3-(acetyl(2,6-dimethylphenyl)carbamoyl)-1-((2,6-dimethylphenyl)amino)-2-naphthoate
molecular weight: 508.2362
Appearance: white solid
Melting point: 74-76 deg.C
Nuclear magnetic resonance hydrogen spectrum:1h NMR (500MHz, Chloroform-d) δ 8.75(s,1H),7.76(d, J ═ 8.0Hz,1H),7.61(d, J ═ 8.6Hz,1H),7.50(t, J ═ 7.4Hz,1H),7.39(s,1H),7.28(d, J ═ 4.4Hz,1H),7.24(d, J ═ 7.3Hz,2H),7.22-7.17(m,1H),7.12-7.04(m,3H),4.35(q, J ═ 7.0Hz,2H),2.45(s,6H),2.13(d, J ═ 11.7Hz,9H),1.36(t, J ═ 7.1Hz,3H), nuclear magnetic resonance spectrum:13C NMR(125MHz,Chloroform-d)δ172.61,171.07,168.20,147.10,140.99,137.16,136.59,136.29,134.63,133.18,129.15,129.09,129.04,128.91,128.64,126.52,126.37,124.99,124.42,117.43,110.01,61.70,25.49,19.27,18.41,14.35；
high-resolution mass spectrometry: HRMS (ESI) Calcd for C32H32N2O4[M+Na]+531.2254,Found:531.2250。
The application is as follows: it has important application in many optical and electronic materials, and is also the backbone of many chiral ligands, and plays an important role in the control of microbial infections.
Example two: 3mL of chlorobenzene was added as a solvent to a 25mL pressure-resistant sealed tube, and then two reactants, propargyl alcohol acetate (0.5mmol) and 2,6-dimethylphenyl isonitrile (1.5mmol), were added to the solvent, the pressure-resistant tube was sealed, the reaction was carried out at 140 ℃, and follow-up detection was carried out by TLC until the end of the reaction. The reaction system was subjected to rotary evaporation under vacuum to give a concentrate, which was separated by column chromatography (eluent: PE: EA ═ 30:1) to give the target product 3b (206mg, 79% yield).
Compound 3b has the structural formula:
the molecular formula is as follows: c33H34N2O4
Chinese naming: 3- (acetyl (2, 6-dimethylphenyl) carbamoyl) -1- ((2, 6-dimethylphenyl) amino) -7-methyl-2-naphthoic acid ethyl ester
English naming:
3-(acetyl(2,6-dimethylphenyl)carbamoyl)-1-((2,6-dimethylphenyl)amino)-7-methyl-2-naphthoate
molecular weight: 522.2519
Appearance: white solid
Melting point: 88-89 ℃.
Nuclear magnetic resonance hydrogen spectrum:1H NMR(500MHz,Chloroform-d)δ8.40(s,1H),7.67(d,J＝8.2Hz,1H),7.40(d,J＝9.5Hz,2H),7.35(dd,J＝8.2,1.6Hz,1H),7.29-7.26(m,1H),7.22(d,J＝7.4Hz,2H),7.08(q,J＝5.3Hz,3H),4.26(q,J＝7.1Hz,2H),2.43(s,6H),2.26(s,3H),2.14(s,9H),1.33(t,J＝7.1Hz,3H).
nuclear magnetic resonance carbon spectrum:13C NMR(125MHz,Chloroform-d)δ172.80,171.18,168.32,145.83,140.85,137.31,136.45,136.27,135.34,133.08,132.56,130.63,129.10,129.02,128.93,128.82,126.85,124.85,123.71,117.87,110.87,61.61,25.70,22.09,19.22,18.43,14.30.
high resolution mass spectrometry: HRMS (ESI) Calcd for C33H34N2O4[M+H]+523.2591,Found:523.2582.
The application is as follows: the chiral ligand has important application in a plurality of optical and electronic materials, is also a skeleton of a plurality of chiral ligands, and plays an important role in controlling microbial infection.
Example three: adding 3mL of chlorobenzene as a solvent into a 25mL pressure-resistant sealed tube, adding two reactants of propargyl alcohol acetate (0.5mmol) and 2,6-dimethylphenyl isonitrile (1.5mmol) into the solvent, sealing the pressure-resistant tube, reacting at 140 ℃, and performing tracking detection by TLC until the reaction is finished. The reaction system was subjected to rotary evaporation under vacuum to give a concentrate, which was separated by column chromatography (eluent: PE: EA ═ 30:1) to give the target product 3c (202mg, 75% yield).
Compound 3c has the structural formula:
the molecular formula is as follows: c33H34N2O5
Chinese naming: 3- (acetyl (2, 6-dimethylphenyl) carbamoyl) -1- ((2, 6-dimethylphenyl) amino) -7-methoxy-2-naphthoic acid ethyl ester
English nomenclature:
3-(acetyl(2,6-dimethylphenyl)carbamoyl)-1-((2,6-dimethylphenyl)amino)-7-methoxy-2-naphthoate
molecular weight: 538.2468
Appearance: white solid
Melting point: 81-82 deg.C
Nuclear magnetic resonance hydrogen spectrum:1H NMR(500MHz,Chloroform-d)δ8.65(s,1H),7.66(d,J＝8.9Hz,1H),7.40(s,1H),7.27(s,1H),7.23(d,J＝7.3Hz,2H),7.16-7.02(m,4H),6.94(s,1H),4.41(q,J＝7.0Hz,2H),3.34(s,3H),2.43(s,6H),2.16(s,9H),1.38(t,J＝7.0Hz,3H).
nuclear magnetic resonance carbon spectrum:13C NMR(125MHz,Chloroform-d)δ172.87,171.14,168.44,158.07,145.87,141.17,137.37,136.21,133.98,133.58,130.36,129.42,129.09,129.00,128.96,127.90,125.02,121.15,118.23,111.18,103.53,61.76,54.73,25.74,19.26,18.42,14.36.
high resolution mass spectrometry: HRMS (ESI) Calcd for C33H34N2O5[M+Na]+561.2360,Found:561.2357.
The application is as follows: the chiral ligand has important application in a plurality of optical and electronic materials, is also a skeleton of a plurality of chiral ligands, and plays an important role in controlling microbial infection.
Example four: adding 3mL of chlorobenzene as a solvent into a 25mL pressure-resistant sealed tube, adding two reactants of propargyl alcohol acetate (0.5mmol) and 2,6-dimethylphenyl isonitrile (1.5mmol) into the solvent, sealing the pressure-resistant tube, reacting at 140 ℃, and performing tracking detection by TLC until the reaction is finished. The reaction system was rotary evaporated under vacuum to give a concentrate, which was isolated by column chromatography (eluent: PE: EA: 30:1) to give the desired product 3d (176mg, 65% yield).
Compound 3d has the structural formula:
the molecular formula is as follows: c32H31ClN2O4
Chinese naming: 3- (acetyl (2, 6-dimethylphenyl) carbamoyl) -7-chloro-1- ((2, 6-dimethylphenyl) amino) -2-naphthoic acid ethyl ester
English nomenclature:
3-(acetyl(2,6-dimethylphenyl)carbamoyl)-7-chloro-1-((2,6-dimethylphenyl)amino)-2-naphthoate
molecular weight: 542.1972
Appearance: white solid
Melting point: 75-76 ℃.
Nuclear magnetic resonance hydrogen spectrum:1H NMR(500MHz,Chloroform-d)δ8.56(s,1H),7.68(d,J＝8.7Hz,1H),7.57(d,J＝1.9Hz,1H),7.42(dd,J＝8.6,2.0Hz,1H),7.30(s,1H),7.27(s,1H),7.23(d,J＝7.5Hz,2H),7.13-7.07(m,3H),4.29(q,J＝7.1Hz,2H),2.42(s,6H),2.14(s,6H),2.05(s,3H),1.33(d,J＝7.1Hz,3H).
nuclear magnetic resonance carbon spectrum:13C NMR(125MHz,Chloroform-d)δ172.49,170.80,167.93,145.91,140.38,137.19,137.03,136.35,133.19,132.99,132.10,130.31,129.34,129.27,129.21,127.10,125.44,123.86,116.72,61.89,25.33,19.24,18.43,14.35,1.16；
high-resolution mass spectrometry: HRMS (ESI) Calcd for C32H31ClN2O4[M+Na]+565.1865,Found:565.1869；
The application is as follows: it has important application in many optical and electronic materials, and is also the backbone of many chiral ligands, and plays an important role in the control of microbial infections.
Example five: 3mL of chlorobenzene was added as a solvent to a 25mL pressure-resistant sealed tube, and then two reactants, propargyl alcohol acetate (0.5mmol) and 2,6-dimethylphenyl isonitrile (1.5mmol), were added to the solvent, the pressure-resistant tube was sealed, the reaction was carried out at 140 ℃, and follow-up detection was carried out by TLC until the end of the reaction. The reaction system was subjected to rotary evaporation under vacuum to give a concentrate, which was separated by column chromatography (eluent: PE: EA: 30:1) to give the objective product 3e (208mg, 71% yield).
Compound 3d has the structural formula:
the molecular formula is as follows: c32H31BrN2O4
Chinese naming: 3- (acetyl (2, 6-dimethylphenyl) carbamoyl) -7-bromo-1- ((2, 6-dimethylphenyl) amino) -2-naphthoic acid ethyl ester
English naming:
3-(acetyl(2,6-dimethylphenyl)carbamoyl)-7-bromo-1-((2,6-dimethylphenyl)amino)-2-naphthoate
molecular weight: 586.1467
Appearance: white solid
Melting point: 84-85 ℃.
Nuclear magnetic resonance hydrogen spectrum:1H NMR(500MHz,Chloroform-d)δ8.58(s,1H),7.75(s,1H),7.60(d,J＝8.7Hz,1H),7.55(dd,J＝8.6,1.8Hz,1H),7.28(d,J＝6.0Hz,2H),7.23(d,J＝7.6Hz,2H),7.10(d,J＝3.4Hz,3H),4.29(q,J＝7.1Hz,2H),2.42(s,6H),2.14(s,6H),2.05(s,3H),1.33(s,3H).
nuclear magnetic resonance carbon spectrum:13C NMR(125MHz,Chloroform-d)δ172.46,170.79,167.90,140.37,137.38,136.36,133.24,131.84,130.33,129.27,129.21,127.19,125.49,120.17,116.69,111.07,61.89,25.32,19.22,18.44,14.36.
high resolution mass spectrometry: HRMS (ESI) Calcd for C32H31BrN2O4[M+Na]+609.1359,Found:609.1346.
The application is as follows: the chiral ligand has important application in a plurality of optical and electronic materials, is also a skeleton of a plurality of chiral ligands, and plays an important role in controlling microbial infection.
Claims (1)
1. A process for preparing a polysubstituted naphthalene derivative, characterized in that it comprises the following steps: dissolving 2, 6-dimethylphenyliisonitrile and propargyl alcohol acetate in 3 ml-5 ml of chlorobenzene according to the molar ratio of 3: 1-2: 1, stirring at 110-140 ℃, and monitoring the reaction by TLC; after the reaction is finished, evaporating the solvent under reduced pressure, and separating and purifying to obtain the polysubstituted naphthalene derivative; the structural formula of the propargyl alcohol acetate is as follows:
wherein R is H, methyl, methoxyl and halogen element; xyl is 2, 6-dimethylphenyl;
the structure of the polysubstituted naphthalene derivative is as follows:
wherein R is H, methyl, methoxyl and halogen element; xyl is 2, 6-dimethylphenyl.
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Non-Patent Citations (3)
| Title |
|---|
| An intramolecular, Pd-mediated a-arylation route to 4-aryl-2-naphthols;Stuart Aiken等;《Tetrahedron Letters》;20150630;第56卷;第4840–4842页 * |
| Au(I)-Catalyzed expeditious access to naphtho[2,3-c]furan-1(3-H)-ones from readily available propargylic ynoates;Ting Li等;《Chem. Commun.》;20180814;第54卷;第10447-10450页 * |
| Electrophilic Carbocyclization of Aryl Propargylic Alcohols: A Facile Synthesis of Diiodinated Carbocycles and Heterocycles;Hai-Tao Zhu等;《Org. Lett.》;20110120;第13卷(第4期);第684-687页 * |
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