CN104478723B - Synthesis naphthalene derivative and the method for benzo-heterocycle compound - Google Patents

Synthesis naphthalene derivative and the method for benzo-heterocycle compound Download PDF

Info

Publication number
CN104478723B
CN104478723B CN201410763995.7A CN201410763995A CN104478723B CN 104478723 B CN104478723 B CN 104478723B CN 201410763995 A CN201410763995 A CN 201410763995A CN 104478723 B CN104478723 B CN 104478723B
Authority
CN
China
Prior art keywords
naphthalene derivative
compound
formula
benzo
synthesis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201410763995.7A
Other languages
Chinese (zh)
Other versions
CN104478723A (en
Inventor
柴永海
康磊
张敏
冯颖乐
吴晏兵
张琦
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shaanxi Normal University
Original Assignee
Shaanxi Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shaanxi Normal University filed Critical Shaanxi Normal University
Priority to CN201410763995.7A priority Critical patent/CN104478723B/en
Publication of CN104478723A publication Critical patent/CN104478723A/en
Application granted granted Critical
Publication of CN104478723B publication Critical patent/CN104478723B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00Preparation of carboxylic acid esters
    • C07C67/30Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54Radicals substituted by carbon atoms having three bonds to heteroatoms, with at the most one to halogen, e.g. ester or nitrile radicals
    • C07D213/55Acids; Esters
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D333/00Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring

Abstract

The invention discloses a kind of method synthesizing naphthalene derivative and benzo-heterocycle compound, the method is that ortho position is had α, the aryl aldehyde of β beta-unsaturated esters and ketone compounds tertiary amine, tertiary phosphine organic micromolecule catalyst catalysis under there is the reaction of similar Mortia Baylis Hillman, and then lose a part water generation naphthalene derivative or benzo-heterocycle compound.Operating procedure of the present invention is simple, and used catalyst is cheap and easy to get, environmental sound, has synthesized a series of naphthalene derivative and benzo-heterocycle compound with preferable yield.

Description

Synthesis naphthalene derivative and the method for benzo-heterocycle compound
Technical field
Naphthalene derivative of the present invention and the synthesis technical field of benzo-heterocycle compound, be specifically related to a kind of with uncle Amine, tertiary phosphine organic micromolecule are catalyst, are reacted by intramolecular similar Mortia-Baylis-Hillman, Synthesis naphthalene derivative and the method for benzo-heterocycle compound.
Background technology
Japanese chemists Mortia in nineteen sixty-eight reported first by α, β-unsaturated compound and electrophilic reagent at tool Have under the catalysis of the tertiary amine of nucleophilicity, tertiary phosphorus species, generate the reaction of α position addition compound product, and then Baylis Report in Deutsche Bundespatent in 1972 with Hillman (therefore this reaction is referred to as Mortia-Baylis-Hillman, It is called for short MBH reaction).This reaction response mild condition, product has polyfunctional group, atom economy.Pass through Intramolecular Mortia-Baylis-Hillman reacts and can synthesize different size of carbocyclic ring and heterocyclic compound, but by It is difficult to preparation, so being applied to the relatively fewer of report in its substrate.
Most of naphthalene derivatives of reporting in recent years and Benzheterocyclic derivatives be synthesized by noble metal, transition Metal or acid catalyzed reaction synthesize.Such as, the activation of catalyst ortho position of Liu group metal Ru in 2003 is Triple carbon-carbon bonds on the benzyne of alkene, and then there is the rearrangement of carbonium ion, synthesize naphthalene derivative (Hung-Chin Shen, Sitaram Pal, Jian-Jou Lian, Rai-Shung Liu.J.AM.CHEM.SOC, 2003,125, 15762-15763);The activation of catalyst triple carbon-carbon bonds of Dean group noble silver in 2006 generate important in Mesosome phenyl allene, has synthesized some naphthalene derivatives (Jing Zhao, Colin O.Hughes, F.Dean Toste. J.AM.CHEM.SOC, 2006,128,7436-7437);The palladium chtalyst carbon of Loh group bivalence in 2010 Carbon three key has synthesized some naphthalene derivatives (Chao Feng, Teck-Peng Loh cleverly.J.AM.CHEM. SOC, 2010,132,17710-17712);Jiang group hydration Tetrafluoroboric acid copper (II) catalysis in 2012 Amine and halo alkynyl benzene have synthesized 1,3-diaminourea naphthalene derivatives (Zhengwang Chen, Wei Zeng, Huanfeng Jiang, Liangxian Liu.Org.Lett, 2012,14,21);Fan group zinc in 2014 The adjacent alkynylbenzonitrile of catalysis has synthesized naphthylamino ester type compound (Yan He, Xinying Zhang, Xuesen Fan. Chem.Commun, 2014,50,5641-5643);Within 2014, Balamurugan group is by fluoroform sulphur Acid catalysis neighbour's alkynyl benzophenone, reaction forms the intermediate of acetal and then [2+2] cyclization, whole reaction 30 to 60 occurs Minute, synthesize naphthalenone (Seetharaman Manojveer, Rengarajan Balamurugan.Org.Lett, 2014,16,1712-1715);Within 2014, ferric chloride is applied to alkynes and adjacent ketone group benzaldehyde generation by Zhu group [4+2] cyclization, with the highest yield synthesized naphthalene derivative (Shifa Zhu, Yelin Xiao, Zhengjiang Guo, Huanfeng Jiang.Org.Lett, 2013,15,4);Within 2011, Majumdar group silver hexafluoroantimonate is urged Change three and be bonded to quinoline derivatives (K.C.Majumdar, Raj Kumar Nandi, Sintu Ganai, Abu Taher.Synlett, 2011,1,116-120);Within 2011, Liu group palladium carbon works as going back of catalyst choice Former nitro with fabulous yield obtained quinoline derivatives (SRui-Guang Xing, Ya-Nan Li, Qiang Liu, Yi-Feng Han, Xia Wei, Jing Li, Bo Zhoua.Synthesis, 2011,13,2066-2072).
Said method is due to expensive catalyst, and to bad environmental, anhydrous and oxygen-free is required strict by reaction condition, reaction Acutely, atom uneconomicalization, product yield is relatively low, limits they application in large-scale industry synthesizes.
Summary of the invention
The technical problem to be solved is to overcome existing naphthalene derivative and benzo-heterocycle compound to close The shortcoming that one-tenth method exists, it is provided that a kind of catalyst is cheap, environmental sound reacts easily operated, product naphthalene nucleus Derivant and the higher synthetic method of benzo-heterocycle compound yield.
Solve above-mentioned technical problem to be the technical scheme is that type I compound is dissolved completely in organic solvent In, back flow reaction under catalyst action, obtain the naphthalene derivative shown in formula II or benzo-heterocycle compound;
In formula, R represents H, halogen, C1~C4Alkyl, C1~C4Any one in alkoxyl;R1Represent H, C1~ C4Any one in alkyl, phenyl, substituted-phenyl, 1-naphthyl;R2Represent C1~C4Alkyl or 1-naphthyl;X1、 X2Any one in the most independent representative C, N, O, S, and X1And X2In at least one be C;m Representing the replacement number of R, its value is the arbitrary integer of 0~2, and n is 1 or 2;
In above-mentioned formula I and formula II, when n is 2, preferably X1、X2All represent C, R represent further H, Br, Any one in Cl, F, methyl, methoxyl group, R1Represent further in H, methyl, phenyl, 1-naphthyl Any one;R2Represent ethyl further.
In above-mentioned formula I and formula II, when n is 1, preferably X1、X2In the most independent representative C, O, S Any one, and X1And X2In at least one be C, R represents H, Br, Cl, F, methyl, first further Any one in epoxide, R1Represent in H, methyl, phenyl, 1-naphthyl further any one;R2Enter one Step represents ethyl.
Above-mentioned type I compound is 1:0.1~0.3 with the mol ratio of catalyst, and described catalyst is tertiary amine, uncle Phosphine compound, such as 1,8-diazabicylo 11 carbon-7-alkene, 1,5-di (hetero) nitrogen bicyclo-[4.3.0] ketone-5-alkene, three second Amine, tributylphosphine etc., preferably 1,8-diazabicylo 11 carbon-7-alkene and 1,5-di (hetero) nitrogen bicyclo-[4.3.0] ketone-5-alkene.
Above-mentioned organic solvent is any one in ethanol, methanol, oxolane, dichloromethane, ether, acetonitrile Kind.
The present invention the most preferably back flow reaction 4~24 hours under catalyst action.
Ortho position, with tertiary amine, tertiary phosphine organic micromolecule as catalyst, is had the aryl of alpha, beta-unsaturated esters by the present invention Aldehyde is reacted by intramolecular similar Mortia-Baylis-Hillman with ketone compounds, and then loses a part water Generate naphthalene derivative or benzo-heterocycle compound.Operating procedure of the present invention is simple, and used catalyst is cheap and easy to get, Environmental sound, has synthesized a series of naphthalene derivative and benzo-heterocycle compound with preferable yield.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in more detail, but protection scope of the present invention is not limited only to these Embodiment.
Embodiment 1
As a example by synthesis 2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 152.7mg (0.7mmol) compound 1,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 113.5mg 2-naphthoic acid ethyl ester, Its yield is 81%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.62 (s, 1H), 8.08 (dd, J=8.4,1.8Hz, 1H), 7.96 (d, J=7.8Hz, 1H), 7.88 (d, J=9Hz, 2H), 7.54-7.6 (m, 2H), 4.45 (q, J=7.2Hz, 2H), 1.46 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 166.8,135.51,132.53,130.96,129.35,128.16,128.09,127.79,127.71,126.60, 125.28,61.10,14.42;ESI-MS:C13H12NaO2([M+Na]+) theoretical value 223.0735, measured value 223.0736。
The compound 1 of the present embodiment is prepared from by following route:
Embodiment 2
In embodiment 1, used 1,8-diazabicylo 11 carbon-7-alkene with equimolar 1,5-di (hetero) nitrogen bicyclo- [4.3.0] ketone-5-alkene is replaced, and other steps are same as in Example 1, obtain 2-naphthoic acid ethyl ester, and its yield is 79%.
Embodiment 3
In embodiment 1, used 1,8-diazabicylo 11 carbon-7-alkene replaces with equimolar tributylphosphine, Other steps are same as in Example 1, obtain 2-naphthoic acid ethyl ester, and its yield is 77%.
Embodiment 4
In embodiment 1, used 1,8-diazabicylo 11 carbon-7-alkene replaces with equimolar triethylamine, its His step is same as in Example 1, obtains 2-naphthoic acid ethyl ester, and its yield is 35%.
Embodiment 5
As a example by synthesis 1-methyl-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 162.5mg (0.7mmol) compound 2,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 127.4mg 1-methyl-2-naphthalene first Acetoacetic ester, its yield is 85%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.14-8.16 (m, 1H), 7.78-7.82 (m, 2H), 7.68 (d, J=8.4Hz, 1H), 7.51-7.55 (m, 2H), 4.41 (q, J=7.2Hz, 2H), 2.91 (s, 3H), 1.42 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 168.88,136.77, 134.56,132.86,128.44,128.30,127.17,126.45,126.07,125.77,125.25,61.03, 15.82,14.36;ESI-MS:C14H14NaO2([M+Na]+) theoretical value 237.0891, measured value 237.0891.
The compound 2 of the present embodiment is prepared from by following route:
Embodiment 6
As a example by synthesis 1-phenyl-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 206mg (0.7mmol) compound 3,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 carbon -7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 183.7mg 1-methyl-2-naphthalene first Acetoacetic ester, its yield is 95%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 7.88-7.93 (m, 3H), 7.59 (d, J=9Hz, 1H), 7.52-7.55 (m, 1H), 7.38-7.48 (m, 4H), 7.30-7.32 (m, 2H), 4.04 (q, J=7.2Hz, 2H), 0.95 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 168.65,141.14, 139.21,134.73,132.58,129.75,128.61,127.91,127.86,127.76,127.72,127.36, 127.28,126.56,125.51,60.83,13.67;ESI-MS:C19H16NaO2([M+Na]+): theoretical Value 299.1048, measured value 299.1052.
The compound 3 of the present embodiment is prepared from by following route:
Embodiment 7
To synthesize 6, as a example by 7-dimethoxy-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 194.8mg (0.7mmol) compound 4,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 158.5mg 6,7-dimethoxy Base-2-naphthoic acid ethyl ester, its yield is 87%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.45 (s, 1H), 7.94 (dd, J=8.4,1.8Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 7.20 (s, 1H), 7.13 (s, 1H), 4.42 (q, J=7.2Hz, 2H), 4.01 (s, 3H), 4.00 (s, 3H), 1.43 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 167.00,151.31,149.97,131.86,129.18,128.27,126.31,126.09,123.98, 107.35,106.07,60.86,55.95,55.92,14.42;ESI-MS:C15H16NaO4([M+Na]+) reason Opinion value: 283.0946, measured value 283.0946.
The compound 4 of the present embodiment is prepared from by following route:
Embodiment 8
To synthesize 1-methyl-6, as a example by 7-dimethoxy-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 204.6mg (0.7mmol) compound 5,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 144mg 1-methyl-6,7- Dimethoxy-2-naphthoic acid ethyl ester, its yield is 75%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 7.71 (d, J=9Hz, 1H), 7.54 (d, J=9Hz, 1H), 7.35 (s, 1H), 7.09 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 4.01 (d, J=12Hz, 6H), 2.87 (s, 1H), 1.42 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 168.95,150.40,149.69,135.24,130.89,128.42,126.56,126.64,124.35,106.70, 104.04,60.83,55.84,55.82,16.04,14.37;ESI-MS:C16H18NaO4([M+Na]+) reason Opinion value 297.1103, measured value 297.1100.
The compound 5 of the present embodiment is prepared from by following route:
Embodiment 9
To synthesize 1-phenyl-6, as a example by 7-dimethoxy-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 248mg (0.7mmol) compound 6,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 carbon -7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 218.9mg 1-phenyl-6,7-bis- Methoxyl group-2-naphthoic acid ethyl ester, its yield is 93%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 7.82 (d, J=8.4Hz, 1H), 7.71 (d, J=8.4Hz, 1H), 7.44-7.47 (m, 2H), 7.41 (tt, J=7.2,1.2Hz, 1H), 7.29-7.31 (m, 2H), 7.42 (s, 1H), 6.84 (s, 1H), 4.03 (q, J=7.2Hz, 2H), 4.00 (s, 3H), 3.69 (s, 3H), 0.95 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 168.66,150.62, 149.71,139.81,139.78,131.18,129.51,128.22,127.93,127.18,126.76,125.90, 124.36,106.27,106.16,60.59,55.91,55.53,13.68.
The compound 6 of the present embodiment is prepared from by following route:
Embodiment 10
As a example by synthesis 7-fluoro-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 165.3mg (0.7mmol) compound 7,21.5uL (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 106.9mg 1-phenyl-6,7- Dimethoxy-2-naphthoic acid ethyl ester, its yield is 70%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.52 (s, 1H), 8.01 (dd, J=8.4,1.2Hz, 1H), 7.87-7.82 (m, 2H), 7.54 (dd, J=9.6,2.4Hz, 1H), 7.34 (td, J=8.6,2.4Hz, 1H), 4.44 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 166.51,161.72,160.09,133.36,133.30,132.44,130.21,130.15,130.11, 130.07,128.83,128.08,124.66,124.64,118.62,118.45,112.31,112.17,61.24, 14.376。
The compound 7 of the present embodiment is prepared from by following route:
Embodiment 11
As a example by synthesis 1-phenyl-7-fluoro-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 218.6mg (0.7mmol) compound 8,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains the 191.5mg 1-fluoro-2-of phenyl-7- Naphthoic acid ethyl ester, its yield is 93%, and structural characterization data are as follows:
1H NM (600MHz, CDCl3) δ: 7.91-7.82 (m, 3H), 7.50-7.40 (m, 3H), 7.32 -7.26 (m, 3H), 7.23-7.19 (m, 1H), 4.04 (q, J=7.2Hz, 2H), 0.94 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 168.45,161.85,160.22,140.35,140.32, 138.66,133.70,133.64,131.64,130.32,130.27,129.65,129.60,128.06,127.57, 127.55,124.81,124.79,117.80,117.63,111.22,111.07,60.93,13.62;ESI-MS: C19H15FNaO2([M+Na]+) theoretical value 317.0954, measured value 317.0962.
The compound 8 of the present embodiment is prepared from by following route:
Embodiment 12
As a example by synthesis 7-chloro-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 176.8mg (0.7mmol) compound 9,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 121.5mg 7-chloro-2-naphthoic acid Ethyl ester, its yield is 74%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.43 (s, 1H), 8.01 (dd, J=8.4,1.2Hz, 1H), 7.84 (s, 1H), 7.77 (d, J=8.4Hz, 1H), 7.72 (d, J=8.4Hz, 1H), 7.45 (dd, J=8.4,1.8Hz, 1H), 4.43 (q, J=7.2Hz, 2H), 1.43 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 166.30,133.56,133.09,132.38,129.86,129.26, 128.94,128.81,127.95,127.82,125.56,61.25,14.37.
The compound 9 of the present embodiment is prepared from by following route:
Embodiment 13
As a example by synthesis 1-naphthyl-2-naphthoic acid ethyl ester, its reaction equation is as follows:
By 241mg (0.7mmol) compound 10,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 224mg 1-naphthyl-2-naphthalene first Acetoacetic ester, its yield is 98%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.07 (d, J=8.4Hz, 1H), 7.98 (d, J=8.4Hz, 1H), 7.95-7.89 (m, 3H), 7.54 (dd, J=8.4,7.2Hz, 1H), 7.51-7.48 (m, 1H), 7.43 (ddd, J=8.2,4.8,3.0Hz, 1H), 7.33 (dd, J=7.2,1.2Hz, 1H), 7.31 (d, J=8.4Hz, 1H), 7.28-7.22 (m, 3H), 3.86-3.74 (m, 2H), 0.53 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 168.05,139.69,137.22,134.80,133.25, 133.17,133.12,129.30,128.04,128.03,128.02,127.88,127.69,127.51,127.05, 126.62,126.21,125.98,125.84,125.69,125.13,60.52,13.18;ESI-MS:C23H18NaO2 ([M+Na]+) theoretical value 349.1204, measured value 349.1202.
The compound 10 of the present embodiment is prepared from by following route:
Embodiment 14
As a example by synthesis 6-Ethyl formate benzothiophene, its reaction equation is as follows:
By 156.9mg (0.7mmol) compound 11,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 86.6mg 6-Ethyl formate benzene Bithiophene, its yield is 60%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.61 (s, 1H), 8.02 (d, J=8.4Hz, 1H), 7.83 (d, J=8.4Hz, 1H), 7.61 (d, J=5.4Hz, 1H), 7.36 (d, J=5.4Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 1.42 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 166.68, 142.80,139.39,130.29,126.44,125.05,124.61,123.76,123.29,61.05,14.38; ESI-MS:C11H10NaSO2([M+Na]+) theoretical value 229.0299, measured value 229.0299.
The compound 11 of the present embodiment is prepared from by following route:
Embodiment 15
As a example by synthesis 7-methyl naphthalene Ethyl formate, its reaction equation is as follows:
By 162.5mg (0.7mmol) compound 12,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 140.9mg 7-methyl naphthalene formic acid Ethyl ester, its yield is 94%, and structural characterization data are as follows:
1H NMR (600MHz, CDCl3) δ: 8.55 (s, 1H), 8.02 (dd, J=9,1.2Hz, 1H), 7.82 (d, J=8.4Hz, 1H), 7.75 (d, J=9Hz, 1H), 7.61 (s, 1H), 7.35 (d, J =8.4Hz, 1H), 4.42 (q, J=7.2Hz, 2H), 2.51 (s, 3H), 1.43 (t, J=7.2Hz, 3H);13C NMR (151MHz, CDCl3) δ: 166.89,138.26,135.75,130.73,130.70, 129.10,128.89,127.36,126.90,126.77,125.35,60.97,21.88,14.41.
The compound 12 of the present embodiment is prepared from by following route:
Embodiment 16
As a example by synthesis 6-Ethyl formate quinoline, its reaction equation is as follows:
By 153.4mg (0.7mmol) compound 12,21.5 μ L (0.14mmol) 1,8-diazabicylo 11 Carbon-7-alkene (DBU) adds in 7mL ethanol, is heated to reflux 12 hours, with silicagel column column chromatography for separation product, Leacheate is the mixed liquor that volume ratio is 1:8 of ethyl acetate and petroleum ether, obtains 98.6mg 6-Ethyl formate quinoline Quinoline, its yield is 70%, and structural characterization data are as follows:
ESI-MS:C12H11NNaO2([M+Na]+) theoretical value 224.0687, measured value 224.0683.
The compound 13 of the present embodiment is prepared from by following route:

Claims (6)

1. the method synthesizing naphthalene derivative, it is characterised in that: type I compound is dissolved completely in organic In solvent, back flow reaction under catalyst action, obtain the naphthalene derivative shown in formula II;
In formula, R represents H, halogen, C1~C4Alkyl, C1~C4Any one in alkoxyl;R1Represent H, C1~ C4Any one in alkyl, phenyl, 1-naphthyl;R2Represent C1~C4Alkyl;X1、X2The most independent generation Any one in table C, N, O, S, and X1And X2In at least one be C;M represents the replacement of R Number, its value is the arbitrary integer of 0~2, and n is 1 or 2;
Above-mentioned catalyst is 1,8-diazabicylo 11 carbon-7-alkene, and described type I compound is rubbed with catalyst That ratio is 1:0.1~0.3.
The method of synthesis naphthalene derivative the most according to claim 1, it is characterised in that: described formula I Any one in H, Br, Cl, F, methyl, methoxyl group is represented with R in formula II.
The method of synthesis naphthalene derivative the most according to claim 2, it is characterised in that: described formula I With R in formula II1Represent in H, methyl, phenyl, 1-naphthyl any one.
Synthesis naphthalene derivative the most according to claim 3 and the method for benzo-heterocycle compound, it is special Levy and be: R in described formula I and formula II2Represent ethyl.
The method of synthesis naphthalene derivative the most according to claim 1, it is characterised in that: by formula I chemical combination Thing is dissolved completely in organic solvent, back flow reaction 4~24 hours under catalyst action, obtains shown in formula II Naphthalene derivative or benzo-heterocycle compound.
The method of synthesis naphthalene derivative the most according to claim 1, it is characterised in that: described is organic Solvent is any one in ethanol, methanol, oxolane, dichloromethane, ether, acetonitrile.
CN201410763995.7A 2014-12-11 2014-12-11 Synthesis naphthalene derivative and the method for benzo-heterocycle compound Expired - Fee Related CN104478723B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410763995.7A CN104478723B (en) 2014-12-11 2014-12-11 Synthesis naphthalene derivative and the method for benzo-heterocycle compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410763995.7A CN104478723B (en) 2014-12-11 2014-12-11 Synthesis naphthalene derivative and the method for benzo-heterocycle compound

Publications (2)

Publication Number Publication Date
CN104478723A CN104478723A (en) 2015-04-01
CN104478723B true CN104478723B (en) 2016-08-24

Family

ID=52753359

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410763995.7A Expired - Fee Related CN104478723B (en) 2014-12-11 2014-12-11 Synthesis naphthalene derivative and the method for benzo-heterocycle compound

Country Status (1)

Country Link
CN (1) CN104478723B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106349269B (en) * 2016-08-24 2018-08-31 浙江美诺华药物化学有限公司 2- (3- fluorine benzyloxy) -5- formylphenylboronic acids and preparation method thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1030749A (en) * 1987-02-09 1989-02-01 帝国化学工业公司 The method for preparing Fungicidal compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1030749A (en) * 1987-02-09 1989-02-01 帝国化学工业公司 The method for preparing Fungicidal compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Enantioselective Synthesis of 2,6-cis-Disubstituted Tetrahydropyrans via a Tandem Catalytic Asymmetric Hydrogenation/Oxa-Michael Cyclization:An Efficient Approach to (-)-Centrolobine;Jian-Hua Xie等;《ORGANIC LETTERS》;20120830;第14卷(第18期);第4758–4761页 *
Synthesis of the Western Half of the Lolicines and Lolitrems;Dylan B. England等;《ORGANIC LETTERS》;20060425;第8卷(第11期);图4和补充信息第5-6页 *

Also Published As

Publication number Publication date
CN104478723A (en) 2015-04-01

Similar Documents

Publication Publication Date Title
Lipowsky et al. Regio‐and Enantioselective Iridium‐Catalyzed Allylic Alkylation with In Situ Activated P, C‐Chelate Complexes
Chen et al. Iridium‐Catalyzed Enantioselective Allylic Substitution of Unstabilized Enolates Derived from α, β‐Unsaturated Ketones
Feng et al. Conjugate Boration of β, β‐Disubstituted Unsaturated Esters: Asymmetric Synthesis of Functionalized Chiral Tertiary Organoboronic Esters
Bonet et al. The selective catalytic formation of β-boryl aldehydes through a base-free approach
Cabrero‐Antonino et al. Iron‐Catalysed Regio‐and Stereoselective Head‐to‐Tail Dimerisation of Styrenes
Chew et al. Enantioselective phospha-Michael addition of diarylphosphines to β, γ-unsaturated α-ketoesters and amides
Li et al. Selectively catalytic hydrodefluorination of perfluoroarenes by Co (PMe 3) 4 with sodium formate as reducing agent and mechanism study
Dong et al. A Convenient and Efficient Rhenium‐Catalyzed Hydrosilylation of Ketones and Aldehydes
Malkov et al. New organocatalysts for the asymmetric reduction of imines with trichlorosilane
Lega et al. Application of pyranoside phosphite-pyridine ligands to enantioselective metal-catalyzed allylic substitutions and conjugate 1, 4-additions
Shen et al. Synthesis of polyfluoroarene-substituted benzofuran derivatives via cooperative Pd/Cu catalysis
Mitsudome et al. Simple and clean synthesis of ketones from internal olefins using PdCl2/N, N-dimethylacetamide catalyst system
Huang et al. Palladium-catalyzed asymmetric 1, 6-addition of diphenylphosphine to (4-aryl-1, 3-butadienylidene) bis (phosphonates) for the synthesis of chiral phosphines
Qiu et al. Generation of Indene Derivatives by Tandem Reactions
Wei et al. Highly Efficient Rhodium-Catalyzed Transfer Hydrogenation of Nitroarenes into Amines and Formanilides
Wang et al. Palladium-catalyzed α-regioselective allylic amination of Morita–Baylis–Hillman acetates with simple aromatic amines
An et al. Metal-free enantioselective addition of nucleophilic silicon to aromatic aldehydes catalyzed by a [2.2] paracyclophane-based N-heterocyclic carbene catalyst
Wu et al. Selective arylation at the vinylic site of cyclic olefins
Mo et al. The applications of palladacycles as transition-metal catalysts in organic synthesis
CN102503883A (en) Method for selectively preparing isoindoline-1-ketone derivative or isoquinoline-1-ketone derivative
CN104478723B (en) Synthesis naphthalene derivative and the method for benzo-heterocycle compound
Umeda et al. Rhodium-catalyzed asymmetric addition of arylboronic acids to 2 H-chromenes leading to 3-arylchromane derivatives
Khan et al. Versatile Catalytic Reactions of Norbornadiene Derivatives with Alkynes
Wang et al. Silver salts and DBU cooperatively catalyzed nucleophilic addition/cyclization of propargylic alcohols with trifluoromethyl ketones
Liu et al. Synthesis of tunable phosphinite–pyridine ligands and their applications in asymmetric hydrogenation

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160824

Termination date: 20191211