CN101638355B - Method for synthesizing multi-substituted 1-naphthol - Google Patents
Method for synthesizing multi-substituted 1-naphthol Download PDFInfo
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- CN101638355B CN101638355B CN2009101013154A CN200910101315A CN101638355B CN 101638355 B CN101638355 B CN 101638355B CN 2009101013154 A CN2009101013154 A CN 2009101013154A CN 200910101315 A CN200910101315 A CN 200910101315A CN 101638355 B CN101638355 B CN 101638355B
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Abstract
The invention provides a method for synthesizing multi-substituted 1-naphthol. At 140 DEG C or 160 DEG C, dimethylbenzene or 1,3,5-trimethylbenzene is used as a solvent, and zincon and a raw material of 2,3-allenoic acid ester have a 1,4-addition reaction and an intramolecular cyclization reaction to obtain a series of multi-substituted 1-naphthol compounds, wherein the zincon and the 2,3-allenoic acid ester firstly have a 1,4-addition reaction to generate a 1,3-conjugated diene zinc oxide salt; then an intramolecular Friedel-Crafts reaction is carried out to obtain a 1-naphthol zinc oxide salt; and a decomposition reaction is carried out to obtain the 1-naphthol. The method does not need a catalyst for the reactions and has simple operation and easy obtaining of the raw material and reagents. Three substituent groups can be simultaneously introduced on the 1-naphthol, and a product is easy to separate and purify, thus the method is suitable for synthesizing various kinds of the multi-substituted 1-naphthol.
Description
Technical field
The present invention relates to a kind of method of polysubstituted 1-naphthols.
Background technology
Naphthols and verivate thereof are one type and important compound, can be used for the synthetic of dyestuff, inhibitor, sanitas, agricultural chemicals, rubber, paint etc., in Chemical Manufacture, have a wide range of applications.Also being used to prepare chiral ligand and many aroma systems compound, is the important midbody of organic synthesis.Also be the basic framework of a lot of natural products simultaneously.But in the naphthol compound of report in the past synthetic, in the polysubstituted 1-naphthols compound method of system comparatively never.Recently bibliographical information is arranged the silica-based benzyne of 3-the Diels-Alder reaction takes place with substituted furans, generate 4 substituted 1-naphthols (Akai, S.; Ikawa, T.; Takayanagi, S.-I.; Morikawa, Y.; Mohri, S.; Tsubakiyama, M.; Egi, M.; Wada, Y.; Kita, Y.Angew.Chem., Int.Ed.2008,47,7673), but its raw material is difficult for preparation, and the while substituting group is confined to 4 of 1-naphthols.
Summary of the invention
The object of the invention is exactly the method for providing convenience, effectively synthesizing the substituted 1-naphthols of polyfunctional group.
The method of synthetic polysubstituted 1-naphthols provided by the invention, with YLENE or 1,3, the 5-trimethylbenzene is a solvent; Zincon and raw material 2,3-join the olefin(e) acid ester and take place 1,4-addition and intramolecular cyclization reaction; Obtain a series of polysubstituted 4-phenyl-1-naphthol compound, zincon is at first with 2, and 3-joins the olefin(e) acid ester and takes place 1; The 4-addition reaction generates 1, the zinc oxonium salt of 3-conjugated diolefine; Intramolecular Friedel-Crafts reaction takes place subsequently obtain 1-naphthols zinc oxonium salt, take place again matter separate the reaction obtain polysubstituted 1-naphthols, reaction formula is following:
R
1Be aryl or hydrogen; R
2Be alkyl; R
3Be halogen or hydrogen; R
4Be alkyl or aryl; Wherein alkyl is C
nH
2n+1, n=1-4 in the formula, aryl is for containing substituent phenyl or containing substituent thienyl; X=Br, I
Synthesis step is:
(1) under nitrogen protection, in reaction tubes, adds solution and solvent xylene or 1,3 of zincon, the 5-trimethylbenzene; Place 140 ℃ or 160 ℃ of oil baths, under nitrogen gas stream, after distillation half a hour, under agitation in reaction tubes, add raw material 2,3-joins the YLENE or 1 of olefin(e) acid ester 1; 3,5-trimethylbenzene solution is 140 ℃ or 160 ℃ of reactions down; Described zincon is aryl zincon or dialkyl group zincon, zincon and 2, and the equivalence ratio that 3-joins the olefin(e) acid ester is 3: 1～6: 1; The solution of described zincon and the amount of solvent ratio are 0.2～0.4 mmole/1 milliliter; Described 2, the amount ratio that 3-joins olefin(e) acid ester and solvent is 0.1 mmole/1 milliliter.
(2) after step (1) reacts completely, reaction tubes is cooled back to room temperature and is cooled to 0 ℃, drip saturated ammonium chloride cancellation reaction; Use extracted with diethyl ether, organic phase is used 5% hydrochloric acid, saturated sodium bicarbonate successively; Anhydrous sodium sulfate drying is used in the saturated common salt washing again, filters; Concentrate, rapid column chromatography obtains polysubstituted 1-naphthol compound 4.
The solvent of organic solvent of the present invention for being difficult for reacting: YLENE or 1,3,5-trimethylbenzene with metal reagent.
Zincon of the present invention is the normal hexane of alkyl zinc reagent or the tetrahydrofuran solution of n-heptane solution and aryl zincon, and aryl is substituted-phenyl or thienyl.
Of the present invention 2,3-join the olefin(e) acid ester be 2,4 disubstituted 2,3-joins olefin(e) acid ester or complete substituted 2,3-joins the olefin(e) acid ester.
Zincon of the present invention and 2, the equivalence ratio that 3-joins the olefin(e) acid ester is 3: 1～6: 1; Dialkyl group zinc solution and 2, the equivalence ratio that 3-joins the olefin(e) acid ester is 3: 1; Aryl halogenation zinc solution or thienylzinc halide solvent and 2, the equivalence ratio that 3-joins the olefin(e) acid ester is 6: 1;
The present invention reacts and adopts very strong couplet ene compound of functional group's loading property and the zincon that is easy to prepare, and is characterized as 2,3,4 functional groups that introducing is different at the 1-naphthols.Wherein, the R of zincon
4Group is introduced in 3 of 1-naphthols, and 2,4 groups that join the olefin(e) acid ester are introduced in 4 and 2 of 1-naphthols.
The present invention relates to a kind of compound method of polysubstituted 1-naphthols, under 140 degrees centigrade or 160 degrees centigrade, with YLENE or 1; 3, the 5-trimethylbenzene is a solvent, zincon and 2; 3-joins olefin(e) acid ester 1 and takes place 1, and 4-addition reaction and intramolecular cyclization reaction obtain a series of polysubstituted 1-naphthol compound 4.Reaction need not catalyzer, and compound method is simple to operate, and raw material and reagent are easy to get, and can on the 1-naphthols, introduce three substituting groups simultaneously, and the product easy separation and easy purification is applicable to synthetic various polysubstituted 1-naphthols.
The present invention has overcome the drawback of traditional method, has the following advantages: 1) reaction need not catalyzer; 2) can introduce different substituents respectively 2,3,4 of 1-naphthols; 3) midbody need not separate; 4) product easy separation and easy purification.
Innovative point of the present invention has been to develop a kind of compound method of polysubstituted 1-naphthols.
The productive rate of the corresponding polysubstituted 1-naphthols of present method gained is 68-93%.
Embodiment
Embodiment 1
Under the nitrogen protection, add tetrahydrofuran solution (2.4 milliliters, 0.5M, 1.2 mmoles) and YLENE (3 milliliters) to the bromophenyl zinc iodide in the reaction tubes successively, place 140 degrees centigrade of oil baths, the original solvents tetrahydrofurane with zincon under nitrogen gas stream steams.After distilling half a hour, under agitation in reaction tubes, add 2-methyl-4-phenyl-2,3-divinyl acetoacetic ester (0.0414 gram; 0.2 xylene solution mmole) (2 milliliters) after 0.5 hour, drips 1 milliliter of saturated ammonium chloride solution cancellation reaction in reaction under 140 degrees centigrade; Naturally be back to room temperature and reduce to zero degree, use extracted with diethyl ether, 5% hydrochloric acid; Saturated sodium bicarbonate, saturated aqueous common salt are respectively washed once, anhydrous sodium sulfate drying.Filter, concentrate, rapid column chromatography, 2-methyl-3-(4 '-bromophenyl)-1-naphthols 0.0523 gram, productive rate is 82%.Product is white solid: Solid; M.p.168.9-169.7 ℃ (hexane/ethyl acetate);
1H NMR (300MHz, CDCl
3) δ 8.18-8.09 (m, 1H), 7.80-7.72 (m, 1H), 7.61-7.53 (m, 2H), 7.52-7.41 (m, 2H), 7.33 (s, 1H), 7.29-7.22 (m, 2H), 5.28 (s, 1H), 2.27 (s, 3H);
13C NMR (CDCl
3, 75MHz) δ 149.1,140.7, and 140.1,132.4,131.2,131.1,127.7,126.0,125.5,123.4,121.2,121.0,120.9,114.8,13.2; MS (EI) m/z (%) 314 (M
+(
81Br), 98.81), 312 (M
+(
79Br), 100); IR (KBr, cm
-1) 3405,3048,3005,1596,1571,1488,1450,1385,1374,1343,1303,1266,1235,1201,1146,1098,1071,1010; Anal.Calcd for C
17H
13BrO:C 65.19, and H 4.18, and Found:C 65.20, H 4.36.
Embodiment 2
Press embodiment 1 described method, different is that used substrate and reagent are: 2-methyl-4,4-phenylbenzene-2; 3-divinyl acetoacetic ester (0.0554 gram, 0.2 mmole), (0.7 milliliter of the hexane solution of zinc ethyl; 0.88M; 0.6 mmole), get 2-methyl 4-ethyl-3-phenyl-1-naphthols 0.0486 gram, productive rate is 93%.Product is white solid: Solid; M.p.85.2-88.1 ℃ (hexane/ethyl acetate);
1H NMR (300MHz, CDCl
3) δ 8.10 (d, J=8.4Hz, 1H), 7.50-7.35 (m, 4H), 7.29-7.17 (m, 4H), 5.22 (s, 1H), 2.56 (q, J=7.5Hz, 2H), 2.42 (s, 3H), 1.01 (t, J=7.5Hz, 3H);
13C NMR (CDCl
3, 75MHz) δ 148.1,140.3, and 139.3,132.3,131.2,130.7,128.1,126.8,126.5,125.3,124.4,122.5,120.5,115.7,24.5,15.0,11.8; MS (EI) m/z (%) 262 (M
+, 100); IR (KBr, cm
-1) 3407,3069,2963,2930,2871,1622,1592,1573,1503,1442,1376,1318,1287,1195,1164,1099,1069,1034; HRMS Calcd for C
19H
18O (M
+): 262.1358, Found:262.1358.
Embodiment 3
Press embodiment 1 described method, different is that solvent for use is 1,3, the 5-trimethylbenzene; Temperature is 160 degrees centigrade; Substrate and reagent are: 2-methyl-2,4-phenylbenzene-2,3-divinyl acetoacetic ester (0.0554 gram; 0.2 mmole); Tetrahydrofuran solution (2.4 milliliters, 0.5M, 1.2 mmoles) to the fluorophenyl zinc iodide; 2-methyl-3-(4 '-fluorophenyl)-4-phenyl-1-naphthols 0.0460 gram, productive rate is 70%.Product is white solid: Solid; M.p.176.3-177.5 ℃ (hexane/ethyl acetate);
1H NMR (300MHz, CDCl
3) δ 8.22 (d, J=8.4Hz, 1H), 7.54-7.44 (m, 2H), 7.38-7.30 (m, 1H), 7.24-7.15 (m, 3H), 7.07-7.02 (m, 2H), 7.00-6.93 (m, 2H), 6.90-6.82 (m, 2H), 5.26 (s, 1H), 2.14 (s, 3H);
13CNMR (CDCl
3, 75MHz) δ 161.2 (d, J=243.8Hz), 148.1,139.4,139.0,136.5 (d, J=3.5Hz); 131.9,131.8,131.7 (d, J=7.4Hz), 131.4,127.5,126.8,126.2; 125.8,125.3,123.4,120.8,115.3,114.5 (d, J=20.4Hz), 13.8;
19F NMR (CDCl
3, 282Hz) δ-116.3; MS (EI) m/z (%) 328 (M
+, 100); IR (KBr, cm
-1) 3592,3448,3065,2925,1598,1562,1506,1445,1370,1264,1205,1153,1096,1012; HRMS Calcd for C
23H
17OF (M
+): 328.1263, Found:328.1265..
Claims (3)
1. the method for a synthetic polysubstituted 1-naphthols is characterized in that with YLENE or 1,3 the 5-trimethylbenzene is a solvent; Zincon and raw material 2,3-join the olefin(e) acid ester and take place 1,4-addition and intramolecular cyclization reaction; Obtain a series of polysubstituted 1-naphthol compound, zincon is at first with 2, and 3-joins the olefin(e) acid ester and takes place 1; The 4-addition reaction generates 1, the zinc oxonium salt of 3-conjugated diolefine; Intramolecular Friedel-Crafts reaction takes place subsequently obtain 1-naphthols zinc oxonium salt, take place again matter separate the reaction obtain polysubstituted 1-naphthols, reaction formula is following:
R
1Be hydrogen; R
2Be alkyl; R
3Be halogen or hydrogen; R
4Be alkyl; Wherein alkyl is C
nH
2n+1, n=1-4 in the formula; Wherein X=Br or I;
Synthesis step is:
1), under nitrogen protection, in reaction tubes, add solution and solvent xylene or 1,3 of zincon; The 5-trimethylbenzene places 140 ℃ or 160 ℃ of oil baths, under nitrogen gas stream the distillation half a hour after; Under agitation in reaction tubes, add raw material 2,3-joins the YLENE or 1,3 of olefin(e) acid ester 1; 5-trimethylbenzene solution is 140 ℃ or 160 ℃ of reactions down; Zincon and 2, the equivalence ratio that 3-joins the olefin(e) acid ester is 3: 1～6: 1; The solution of described zincon and the amount of solvent ratio are 0.2～0.6 mmole/1 milliliter; Described 2, the amount ratio that 3-joins olefin(e) acid ester and solvent is 0.1 mmole/1 milliliter;
2), after step (1) reacts completely, reaction tubes is cooled back to room temperature and is cooled to 0 ℃, drip saturated ammonium chloride cancellation reaction; Use extracted with diethyl ether, organic phase is used 5% hydrochloric acid, saturated sodium bicarbonate successively; Anhydrous sodium sulfate drying is used in the saturated common salt washing again, filters; Concentrate, rapid column chromatography obtains polysubstituted 1-naphthol compound 4.
2. the method for synthetic polysubstituted 1-naphthols according to claim 1 is characterized in that reacting used zincon solution the normal hexane or the n-heptane solution that are dialkyl group zinc.
3. the method for synthetic polysubstituted 1-naphthols according to claim 1 is characterized in that dialkyl group zincon and 2, and the equivalence ratio that 3-joins the olefin(e) acid ester is 6: 1.
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Non-Patent Citations (2)
| Title |
|---|
| Zhan Lu, et al..Highly Regio- and Stereoselective Double Michael Addition-Cyclization of 2,3-Allenoates with Organozinc Compounds: Efficient Synthesis of 5-Benzylidenecyclohex-2-enones.《Angew. Chem.》.2008,第120卷第6134-6137页. * |
| ZhanLu et al..Highly Regio- and Stereoselective Double Michael Addition-Cyclization of 2 |
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