CN101974004A - Heterocyclic compound and preparation method thereof - Google Patents

Heterocyclic compound and preparation method thereof Download PDF

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CN101974004A
CN101974004A CN2010105125325A CN201010512532A CN101974004A CN 101974004 A CN101974004 A CN 101974004A CN 2010105125325 A CN2010105125325 A CN 2010105125325A CN 201010512532 A CN201010512532 A CN 201010512532A CN 101974004 A CN101974004 A CN 101974004A
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compound
alkyl
aromatic base
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纪顺俊
徐小平
朱旭
孙昌
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Suzhou University
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Suzhou University
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Abstract

The invention provides a heterocyclic compound and a preparation method thereof. The heterocyclic compound comprises a furanoindole framework, and the preparation method comprises the following steps of: a) mixing o-halogen benzaldehyde, a hydroxyl-containing compound and an isonitrile compound, reacting under reflux to generate an intermediate product; and b) continuing the reflux reaction of the intermediate product under the condition of taking cuprous halide, L-proline and an alkaline inorganic compound as catalysts so as to prepare the heterocyclic compound. The method can prepare the heterocyclic compound with the furanoindole framework only by two steps of reactions and can carry out the second step of reaction without separating and purifying the intermediate product so as to realize one-pot synthesis. In the invention, the process flow is short, consists of fewer steps and requires simple operation, the cost is low, and thus, the method is suitable for industrial production. In addition, the furanoindole framework-containing heterocyclic compound which comprises different functional groups can be prepared by using the hydroxyl-containing compound and the isonitrile compound, which have different functional groups.

Description

Heterogeneous ring compound and preparation method thereof
Technical field
The present invention relates to the organic compound technical field, relate in particular to a kind of heterogeneous ring compound and preparation method thereof.
Background technology
Indoles is the compound of pyrroles and benzo connection, claims benzopyrrole again, has formula (VII) structure:
Figure BSA00000310453400011
Indole ring is that occurring in nature exists the most general heterocycle, and the compound that contains indole ring has wide biological activity, as has effect such as antimycotic, antiviral, antitumor, anxiety.As: indole ring is the primary structure with indomethacin of formula (VII-a) structure, and indomethacin is a kind of potent anodyne, and its English name is Indomethacin, and trade name is an INDOMETHACIN; Have the risatriptan (Rizatriptan) of formula (VII-b) structure, the core texture with Sumatriptan succinate (SumatriptanSuccinate) of formula (VII-c) structure is indole ring, these two kinds of medicines can be used for the treatment of migraine; Melatonin with formula (VII-d) structure is a pineal gland excretory chemical substance, contain the indole ring structure, and have physiological action widely, as hormone secretion, deep-well-internal secretion-immunomodulatory, biorhythm, delay senility, Green Tea Extract damage, calmness, analgesia, hypnosis, effect such as anticonvulsion.
Figure BSA00000310453400012
Furans is the simplest oxygen five joint heterogeneous ring compounds that contain, and has formula (VIII) structure:
The furans biologically active extensively is present in the compound and natural product with pharmacology physiologically active.Furfuran compound has wider antibacterial range, can suppress the growth and breeding of multiple gram-positive microorganism and negative bacterium, and important researching value is arranged in pharmaceutical chemistry, chemicobiology and natural product chemistry.As furans is the primary structure with medicine Ranitidine HCL (ranitidine) of formula (VIII-a) structure, and Ranitidine HCL can be used for treating stomach ulcer; Primary structure with sterilant Nifurazolidone of formula (VIII-b) structure also is a furan nucleus.
Figure BSA00000310453400022
Prior art discloses the synthetic method of multiple furfuran compound, generates new furfuran compound as existing furan nucleus is transformed; Perhaps be the synthetic furfuran compound of catalyst etc., under the catalysis of cuprous iodide, can synthesize multiple furan derivatives (Barluenga J, Riesgo L as the propargyl alcohol ester with the transition metal, Vicente R, et al.J.Am.Chem.Soc.2008,130,13528-13529).Prior art also discloses the synthetic method of multiple Benzazole compounds, as passing through with (Guy R.Humphrey and Jeffrey T.Kuethe.Chem.Rev.2006 such as the catalytic linked reaction synthesis of indole of noble metal catalyst compounds, 106,1875-2911).But the report of indole ring and furan nucleus being introduced simultaneously synthetic compound with furo indoles skeleton in the molecular structure is actually rare.
The equal biologically active of indole ring and furan nucleus, the compound with furo indoles skeleton can have the biological activity of indole ring and furan nucleus simultaneously, and some compound can also show particular performances.As application number is that the Chinese patent literature of 200680007769.X discloses a kind of compound with cumarone diindyl skeleton as potassium channel openers, this compound prepares by following steps: salicyclic acid derivatives add in the presence of the sulfuric acid of methanol solvate with bromoethyl acetate generation condensation reaction after, obtain first intermediate product after removing hydrogen bromide and ethyl; The first intermediate product generation cyclization generates second intermediate product in the presence of diacetyl oxide or sodium acetate; According to Brigit Fischer (Schmidt)-indole reaction (Fisher-indolereaction), in the presence of ethanol or p-TsOH solvent, the phenylhydrazine that the second intermediate product coupling replaces obtains having the compound of cumarone diindyl skeleton.But this synthetic method craft flow process complexity, various, the complex operation of step.
Summary of the invention
In view of this, technical problem to be solved by this invention is to provide a kind of heterogeneous ring compound and preparation method thereof, heterogeneous ring compound provided by the invention has furo indoles skeleton, preparation method's technical process provided by the invention is simple, step is less, can make multiple heterogeneous ring compound with furo indoles skeleton.
The invention provides a kind of compound with formula (I) structure:
Figure BSA00000310453400031
Wherein, R is alkyl or aromatic base;
R 2Be hydrogen, alkyl or aromatic base.
The present invention also provides a kind of compound with formula (II) structure:
Figure BSA00000310453400032
Wherein, R is alkyl or aromatic base;
R 3Be hydrogen, alkyl or aromatic base;
R 4Be hydrogen, alkyl or aromatic base.
The present invention also provides a kind of compound with formula (III) structure:
Figure BSA00000310453400041
Wherein, R is alkyl or aromatic base;
R 5Be hydrogen, alkyl or aromatic base.
The present invention also provides a kind of preparation method of heterogeneous ring compound, comprising:
A) adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate are mixed, back flow reaction generates intermediate product, and described hydroxy-containing compounds has formula (IV), formula V or formula (VI) structure:
Figure BSA00000310453400042
Wherein, R 2Be hydrogen, alkyl or aromatic base;
R3 is hydrogen, alkyl or aromatic base;
R 4Be hydrogen, alkyl or aromatic base;
R 5Be hydrogen, alkyl or aromatic base;
B) be to continue back flow reaction under the condition of catalyzer with described intermediate product, obtain heterogeneous ring compound at cuprous halide, L-proline(Pro) and alkaline inorganic compound.
Preferably, described hydroxy-containing compounds is 4 hydroxy coumarin, 4-hydroxy-n-toluquinoline-2-ketone or 2 hydroxy naphthalene quinone.
Preferably, described adjacent halobenzene formaldehyde is adjacent bromobenzaldehyde or adjacent benzaldehyde iodine.
Preferably, described carbomethoxyisopropyl isonitrate is tert-butyl isonitrile, cyclohexyl isonitrile or 2,6-xylyl isonitrile.
Preferably, described cuprous halide is a cuprous iodide.
Preferably, described alkaline inorganic compound is salt of wormwood or cesium carbonate.
Preferably, the mol ratio of described adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate is 1～2: 1～2: 1.1～2.5.
Preferably, the mol ratio of described cuprous halide, L-proline(Pro), alkaline inorganic compound and described hydroxy-containing compounds is 0.05～0.15: 0.10～0.25: 1.5～3: 1.
Preferably, in the described step a), the temperature of described back flow reaction is 90 ℃～120 ℃, and the time of described back flow reaction is 2h～30h.
Compared with prior art, the present invention at first mixes adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate, refluxes and carries out the polycomponent cascade reaction, obtains intermediate product; Then described intermediate product is transferred to and continued in the catalyst system of cuprous halide, L-proline(Pro) and alkaline inorganic compound to reflux, intramolecular ell graceful (Ulmann) linked reaction takes place, obtain having the heterogeneous ring compound of furo indoles skeleton.The present invention only needs two-step reaction can make the heterogeneous ring compound with furo indoles skeleton, and need not that described intermediate product is separated purification and can carry out the second step reaction, promptly can " one kettle way " synthesize, not only technical process is simple, step is few, simple to operate, and with low cost, be suitable for suitability for industrialized production.In addition, in synthetic method provided by the invention, by hydroxy-containing compounds and the carbomethoxyisopropyl isonitrate that selection has different functional groups, the heterogeneous ring compound that contains furo indoles skeleton that can obtain having different functional groups.
Description of drawings
The molecular structure of the heterogeneous ring compound that Fig. 1 provides for the embodiment of the invention 1.
Embodiment
The invention provides a kind of preparation method of heterogeneous ring compound, comprising:
A) adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate are mixed, back flow reaction generates intermediate product, and described hydroxy-containing compounds has formula (IV), formula V or formula (VI) structure:
Wherein, R 2Be hydrogen, alkyl or aromatic base;
R 3Be hydrogen, alkyl or aromatic base;
R 4Be hydrogen, alkyl or aromatic base;
R 5Be hydrogen, alkyl or aromatic base;
B) be to continue back flow reaction under the condition of catalyzer with intermediate product, obtain heterogeneous ring compound at cuprous halide, L-proline(Pro) and alkaline inorganic compound.
Among the present invention, described adjacent halobenzene formaldehyde is preferably adjacent bromobenzaldehyde or adjacent benzaldehyde iodine, more preferably adjacent bromobenzaldehyde.
Among the present invention, described hydroxy-containing compounds needs to have following structure at least:
Figure BSA00000310453400062
Wherein, dotted portion represent with-COH=C-CO-constitute ring texture, remove-part the COH=C-CO-, this dotted portion and-COH=C-CO-can constitute aromatic nucleus, also can constitute heterocycle.In the present invention, described oxy-compound is compound with formula (IV), formula V or formula (VI) structure, be preferably (IV-a) structure that has formula 4 hydroxy coumarin, have the 4-hydroxy-n-toluquinoline-2-ketone of formula (V-a) structure or 2 hydroxy naphthalene quinone with formula (VI-a) structure:
Among the present invention, described carbomethoxyisopropyl isonitrate has the R-NC structure, and wherein, R is alkyl or aromatic base; Described carbomethoxyisopropyl isonitrate is preferably tert-butyl isonitrile, cyclohexyl isonitrile or 2,6-xylyl isonitrile.
α-addition reaction can take place in described carbomethoxyisopropyl isonitrate, and after adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate were mixed, three component generation cascade reactions obtained intermediate product, react as follows:
According to the present invention, described adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate carry out back flow reaction in organic solvent, and the temperature of described back flow reaction is preferably 90 ℃～120 ℃, more preferably 95 ℃～115 ℃, most preferably are 100 ℃～115 ℃; The time of described back flow reaction is preferably 2h～30h, and more preferably 4h～25h most preferably is 15h～25h.Described back flow reaction is carried out under protection of inert gas.The present invention does not have particular restriction to described organic solvent, is preferably benzene or toluene, more preferably toluene.
In order to react fully, fully, the mol ratio of described adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate is preferably 1～2: 1～2: 1.1～2.5, more preferably 1～2: 1～2: 1.2～2.2, most preferably be 1～2: 1～2: 1.5～2.2.
After obtaining intermediate product, need not described intermediate product is separated, purifies, directly, continue back flow reaction transferring in the catalyst system of cuprous halide, L-proline(Pro) and alkaline inorganic compound after the reacted reaction mixture cooling.Described intermediate product issues living intramolecular ell graceful (Ulmann) linked reaction in the katalysis of cuprous iodide, generates the heterogeneous ring compound with furo indoles skeleton, reacts as follows:
Figure BSA00000310453400073
According to the present invention, the mol ratio of described cuprous halide, L-proline(Pro), alkaline inorganic compound and described hydroxy-containing compounds is preferably 0.05～0.15: 0.10～0.25: 1.5～3: 1, more preferably 0.08～0.13: 0.12～0.23: 1.8～2.8: 1, most preferably be 0.10～0.12: 0.15～0.20: 2～2.5: 1.In catalyst system provided by the invention, described cuprous halide is main catalyzer, and the catalysis intermediate product carries out the graceful linked reaction of intramolecular ell; The L-proline(Pro) is a part, and alkaline inorganic compound mainly provides alkaline environment.Described cuprous halide is preferably cuprous chloride, cuprous bromide or cuprous iodide, more preferably cuprous iodide; Described alkaline inorganic compound includes but not limited to potassium hydroxide, salt of wormwood, cesium carbonate, sodium hydroxide, yellow soda ash etc., is preferably salt of wormwood or cesium carbonate.
According to the present invention, described intermediate product carries out back flow reaction in organic solvent when catalyst system exists, and generates the heterogeneous ring compound with furo indoles skeleton.According to the present invention, the temperature of described back flow reaction is preferably 90 ℃～120 ℃, more preferably 95 ℃～115 ℃, most preferably is 100 ℃～115 ℃; The time of described back flow reaction is preferably 10h～40h, and more preferably 20h～30h most preferably is 22h～28h.Described back flow reaction is carried out under protection of inert gas.The present invention does not have particular restriction to described organic solvent, is preferably benzene or toluene, more preferably toluene.
After generation has the heterogeneous ring compound of furo indoles skeleton, utilize method decompression well known to those skilled in the art to remove organic solvent, use dichloromethane extraction then, use anhydrous magnesium sulfate drying again, obtain having the pure product of heterogeneous ring compound of furo indoles skeleton then behind the column chromatography.
Compared with prior art, the present invention at first mixes adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate, refluxes and carries out the polycomponent cascade reaction, obtains intermediate product; Then described intermediate product is transferred to and continued in the catalyst system of cuprous halide, L-proline(Pro) and alkaline inorganic compound to reflux, intramolecular ell graceful (Ulmann) linked reaction takes place, obtain having the heterogeneous ring compound of furo indoles skeleton.The present invention only needs two-step reaction can make the heterogeneous ring compound with furo indoles skeleton, and need not that described intermediate product is separated purification and can carry out the second step reaction, promptly can " one kettle way " synthesize, not only technical process is simple, step is few, simple to operate, and with low cost, be suitable for suitability for industrialized production.
The heterogeneous ring compound with furo indoles skeleton that the present invention obtains has the biological activity of furan nucleus and indole ring simultaneously, as antibiotic etc., can be used as sterilant.
The present invention also provides a kind of heterogeneous ring compound formula (XI) structure, that have furo indoles skeleton that has:
Figure BSA00000310453400091
Wherein, dotted portion represent with-C=C-CO-constitute ring texture, except that the part the-C=C-CO-, this dotted portion can constitute aromatic nucleus with-C=C-CO-, also can constitute heterocycle, this dotted portion can for-C=C-O-,-C=C-N-,-CO-C=C-; R is alkyl or aromatic base.
This heterogeneous ring compound with furo indoles skeleton can be synthetic according to the synthetic method that technique scheme provides, by hydroxy-containing compounds and carbomethoxyisopropyl isonitrate that selection has different functional groups, the heterogeneous ring compound with furo indoles skeleton that obtains has different functional groups.
When being raw material with the hydroxy-containing compounds with formula (IV) structure, the heterogeneous ring compound with furo indoles skeleton that obtains by above-mentioned synthetic method has formula (I) structure:
Figure BSA00000310453400092
Wherein, R is alkyl or aromatic base, is preferably cyclohexyl, the tertiary butyl or xylyl;
R 2For hydrogen, alkyl or aromatic base, be preferably hydrogen.
When being raw material with the hydroxy-containing compounds with formula V structure, the heterogeneous ring compound with furo indoles skeleton that obtains by above-mentioned synthetic method has formula (II) structure:
Figure BSA00000310453400093
Wherein, R is alkyl or aromatic base, is preferably cyclohexyl, the tertiary butyl or xylyl;
R 3For hydrogen, alkyl or aromatic base, be preferably hydrogen;
R 4For hydrogen, alkyl or aromatic base, be preferably alkyl, more preferably methyl.
When being raw material with the hydroxy-containing compounds with formula (VI) structure, the heterogeneous ring compound with furo indoles skeleton that obtains by above-mentioned synthetic method has formula (III) structure:
Figure BSA00000310453400101
Wherein, R is alkyl or aromatic base, is preferably cyclohexyl, the tertiary butyl or xylyl;
R 5For hydrogen, alkyl or aromatic base, be preferably hydrogen.
Heterogeneous ring compound with furo indoles skeleton provided by the invention has the biological activity of furan nucleus and indole ring simultaneously, as antibiotic etc., can be used as sterilant.
In order to further specify the present invention, heterogeneous ring compound provided by the invention and preparation method thereof is described in detail below in conjunction with embodiment.
Each raw material in the embodiment of the invention is from the market to be buied.
Embodiment 1
With the adjacent bromobenzaldehyde of 1mmol4-Hydroxycoumarin, 1mmol and 1.2mmol tert-butyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 24h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature, removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography; described product is a N-tertiary butyl indoles also [2; 3-b] furo [3,2-c] tonka bean camphor, reaction formula is as follows:
Figure BSA00000310453400111
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.98 (s, 9H, CH 3), 7.26-7.29 (m, 2H, ArH), 7.31-7.35 (m, 1H, ArH), 7.43-7.47 (m, 2H, ArH), 7.70-7.72 (m, 1H, ArH), 7.84 (d, J=7.6Hz, 1H, ArH), 8.14 (d, J=5.2Hz, 1H, ArH) ppm.
With model is that the X ray single crystal diffractometer of Rigaku Mercury CCD carries out the X ray single crystal diffraction to described product, obtain the molecular structure of described product according to diffracting spectrum, the result is referring to Fig. 1, the molecular structure of the heterogeneous ring compound that Fig. 1 provides for the embodiment of the invention 1.As shown in Figure 1, described product is also [2,3-b] furo [3,2-c] tonka bean camphor of N-tertiary butyl indoles.
Embodiment 2
With the adjacent benzaldehyde iodine of 1mmol4-Hydroxycoumarin, 1mmol and 1.2mmol cyclohexyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 24h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is also [2,3-b] furo [3,2-c] tonka bean camphor of N-cyclohexyl indole, and reaction formula is as follows:
Figure BSA00000310453400112
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.42-1.55 (m, 3H, CH 2), 1.86-1.90 (m, 1H, CH 2), 2.03-2.06 (m, 2H, CH 2), 2.14-2.22 (m, 4H, CH 2), 4.38-4.44 (m, 1H, CH), 7.28-7.39 (m, 3H, ArH), 7.44-7.48 (m, 3H, ArH), 7.94 (d, J=7.6Hz, 1H, ArH), 8.12 (d, J=8.0Hz, 1H, ArH) ppm.
Embodiment 3
With adjacent bromobenzaldehyde of 1mmol4-Hydroxycoumarin, 1mmol and 1.2mmol2,6-xylyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 24h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is N-2, and 6-xylyl indoles is [2,3-b] furo [3,2-c] tonka bean camphor also, and reaction formula is as follows:
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=2.06 (s, 6H, CH 3), 7.01 (d, J=8.0Hz, 1H, ArH), 7.32-7.41 (m, 5H, ArH), 7.44-7.55 (m, 3H, ArH), 7.86 (d, J=8.0Hz, 1H, ArH), 8.24 (d, J=7.6Hz, 1H, ArH) ppm.
Embodiment 4
With the adjacent bromobenzaldehyde of 1mmolN-toluquinoline-2-ketone, 1mmol and 1.2mmol tert-butyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 16h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is also [2,3-b] furo [3,2-c] N-toluquinoline-2-ketone of N-tertiary butyl indoles, and reaction formula is as follows:
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.94 (s, 9H, CH 3), 3.80 (s, 3H, NCH 3), 7.24-7.26 (m, 2H, ArH), 7.39-7.43 (m, 1H, ArH), 7.58-7.62 (m, 1H, ArH), 7.69-7.71 (m, 1H, ArH), 7.87-7.89 (m, 1H, ArH), 7.80-8.03 (m, 2H, ArH) ppm.
Embodiment 5
With the adjacent benzaldehyde iodine of 1mmolN-toluquinoline-2-ketone, 1mmol and 1.2mmol cyclohexyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 16h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is also [2,3-b] furo [3,2-c] N-toluquinoline-2-ketone of N-cyclohexyl indole, and reaction formula is as follows:
Figure BSA00000310453400131
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.65-1.70 (m, 2H, CH 2), 1.93-1.97 (m, 1H, CH 2), 2.01-2.13 (m, 2H, CH 2), 2.22-2.30 (m, 5H, CH 2), 3.97 (s, 3H, NCH 3), 4.44-4.52 (m, 1H, CH), 7.36-7.44 (m, 3H, ArH), 7.51-7.53 (m, 1H, ArH), 7.56-7.61 (m, 2H, ArH), 8.15 (d, J=7.6Hz, 1H, ArH), 8.29 (d, J=8.8Hz, 1H, ArH) ppm.
Embodiment 6
With adjacent benzaldehyde iodine of 1mmolN-toluquinoline-2-ketone, 1mmol and 1.2mmol2,6-xylyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 4h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is N-2, and 6-xylyl indoles is [2,3-b] furo [3,2-c] N-toluquinoline-2-ketone also, and reaction formula is as follows:
Figure BSA00000310453400141
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.93 (s, 6H, CH 3), 3.80 (s, 3H, NCH 3), 6.93 (d, J=8.4Hz, 1H, ArH), 7.24-7.34 (m, 3H, ArH), 7.37-7.40 (m, 2H, ArH), and 7.45-7.48 (m, 1H, ArH), 7.54-7.58 (m, 1H, ArH), 7.68 (d, J=8.4Hz, 1H, ArH), 7.88 (d, J=7.6Hz, 1H, ArH), 8.05 (d, J=7.6Hz, 1H, ArH) ppm.
Embodiment 7
With the adjacent bromobenzaldehyde of 1mmol2-hydroxyl naphthoquinone, 1mmol and 1.2mmol tert-butyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 4h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is also [2,3-b] furo [2,3-b] naphthoquinones of N-tertiary butyl indoles, and reaction formula is as follows:
Figure BSA00000310453400142
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.75 (s, 9H, CH 3), 7.13-7.23 (m, 2H, ArH), 7.63-7.71 (m, 2H, ArH), 7.76 (d, J=8.4Hz, 1H, ArH), 7.85 (d, J=7.2Hz, 1H, ArH), 7.89-7.93 (m, 2H, ArH) ppm.
Embodiment 8
With the adjacent benzaldehyde iodine of 1mmolN-toluquinoline-2-ketone, 1mmol and 1.2mmol cyclohexyl isonitrile under protection of inert gas, in the time of 110 ℃ in toluene solvant back flow reaction 16h, obtain reaction mixture; Described reaction mixture is cooled to room temperature; and under protection of inert gas, transfer to in the closed system that contains 0.1mmolCuI, 0.2mmolL-proline(Pro) and 2mmol salt of wormwood; being warming up to 110 ℃ is that solvent continues back flow reaction 24h with toluene; after being cooled to room temperature; removal of solvent under reduced pressure will obtain product behind the extraction of crude product process, drying, the column chromatography.Described product is also [2,3-b] furo [2,3-b] naphthoquinones of N-cyclohexyl indole, and reaction formula is as follows:
Figure BSA00000310453400151
Described product is carried out the nucleus magnetic resonance test, and its proton nmr spectra is as follows: 1H NMR (400MHz, CDCl 3) δ=1.42-1.54 (m, 3H, CH 2), 1.81-1.84 (m, 1H, ArH), 2.01-2.04 (m, 2H, CH 2), 2.17-2.22 (m, 4H, CH 2), 4.33-4.40 (m, 1H, CH), 7.31-7.46 (m, 3H, ArH), 7.67-7.77 (m, 2H, ArH), 8.18-8.25 (m, 3H, ArH) ppm.
The explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof.Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of claim of the present invention.

Claims (12)

1. the compound that has formula (I) structure:
Figure FSA00000310453300011
Wherein, R is alkyl or aromatic base;
R 2Be hydrogen, alkyl or aromatic base.
2. the compound that has formula (II) structure:
Figure FSA00000310453300012
Wherein, R is alkyl or aromatic base;
R 3Be hydrogen, alkyl or aromatic base;
R 4Be hydrogen, alkyl or aromatic base.
3. the compound that has formula (III) structure:
Wherein, R is alkyl or aromatic base;
R 5Be hydrogen, alkyl or aromatic base.
4. the preparation method of a heterogeneous ring compound comprises:
A) adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate are mixed, back flow reaction generates intermediate product, and described hydroxy-containing compounds has formula (IV), formula V or formula (VI) structure:
Figure FSA00000310453300021
Wherein, R 2Be hydrogen, alkyl or aromatic base;
R3 is hydrogen, alkyl or aromatic base;
R 4Be hydrogen, alkyl or aromatic base;
R 5Be hydrogen, alkyl or aromatic base;
B) be to continue back flow reaction under the condition of catalyzer with described intermediate product, obtain heterogeneous ring compound at cuprous halide, L-proline(Pro) and alkaline inorganic compound.
5. preparation method according to claim 4 is characterized in that, described hydroxy-containing compounds is 4 hydroxy coumarin, 4-hydroxy-n-toluquinoline-2-ketone or 2 hydroxy naphthalene quinone.
6. preparation method according to claim 4 is characterized in that, described adjacent halobenzene formaldehyde is adjacent bromobenzaldehyde or adjacent benzaldehyde iodine.
7. preparation method according to claim 4 is characterized in that, described carbomethoxyisopropyl isonitrate is tert-butyl isonitrile, cyclohexyl isonitrile or 2,6-xylyl isonitrile.
8. preparation method according to claim 4 is characterized in that, described cuprous halide is a cuprous iodide.
9. preparation method according to claim 4 is characterized in that, described alkaline inorganic compound is salt of wormwood or cesium carbonate.
10. preparation method according to claim 4 is characterized in that, the mol ratio of described adjacent halobenzene formaldehyde, hydroxy-containing compounds and carbomethoxyisopropyl isonitrate is 1～2: 1～2: 1.1～2.5.
11. preparation method according to claim 4 is characterized in that, the mol ratio of described cuprous halide, L-proline(Pro), alkaline inorganic compound and described hydroxy-containing compounds is 0.05～0.15: 0.10～0.25: 1.5～3: 1.
12. preparation method according to claim 4 is characterized in that, in the described step a), the temperature of described back flow reaction is 90 ℃～120 ℃, and the time of described back flow reaction is 2h～30h.
CN2010105125325A 2010-10-09 2010-10-09 Heterocyclic compound and preparation method thereof Pending CN101974004A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102335233A (en) * 2011-08-08 2012-02-01 南京林业大学 Polyphenol extract of trembling poplar as well as extraction method and application thereof
CN110655524A (en) * 2019-10-24 2020-01-07 江苏师范大学 Naphthoquinone pyranoindole derivatives, and preparation method and application thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102335233A (en) * 2011-08-08 2012-02-01 南京林业大学 Polyphenol extract of trembling poplar as well as extraction method and application thereof
CN102335233B (en) * 2011-08-08 2013-08-07 南京林业大学 Polyphenol extract of trembling poplar as well as extraction method and application thereof
CN110655524A (en) * 2019-10-24 2020-01-07 江苏师范大学 Naphthoquinone pyranoindole derivatives, and preparation method and application thereof

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