CN103554023B - The synthetic method of acridine derivatives and the polycyclic acridine derivative of synthesis - Google Patents
The synthetic method of acridine derivatives and the polycyclic acridine derivative of synthesis Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/02—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems with only hydrogen, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
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- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
- C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
- C07D219/06—Oxygen atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The synthetic method of acridine derivatives of the present invention and the polycyclic acridine derivative of synthesis, belong to the technical field of compou nd synthesis method.Take o fluorobenzaldehyde as raw material, through imines condensation, the adjacent aryl amine Schiff 's base of arylamine nucleophilic substitution synthesizing series.The adjacent aryl amine Schiff 's base of series is substrate, at ZnCl
2effect under, there is intramolecular cyclization, virtueization react, high productivity synthesis acridine derivatives.Raw material of the present invention is common industrial chemicals, and reaction solvent is tetrahydrofuran (THF), and the retortable recycling of solvent, be convenient to reduce costs; Temperature of reaction is 50-80 degree, and reaction conditions is gentle; Post-reaction treatment is simple, and reaction conversion ratio up to 99%, can be convenient to large-scale synthesis.Acridine derivatives synthesized by the inventive method is the heteroaromatic compound that a class has significant application value.
Description
Technical field
The present invention relates at ZnCl
2the new synthetic method of the lower adjacent aryl amine Schiff 's base generation intramolecular cyclization synthesis acridine derivatives of effect, belongs to the technical field of compou nd synthesis method.
Background technology
Acridine compound is used to pigment and dyestuff at 19th-century and is that people know, and its corrosion-resistant also be it is found that in earlier 1800s, and then some of them derivative is because it is antibacterial, antimalarial performance is widely used during the World War I.Subsequently, this compounds due to its widely purposes attracted the broad interest of people.Most of acridine compound has biological activity, can be used for anti-inflammatory, antibacterial, antimalarial, anticancer etc.; Acridine ring has larger conjugate planes, there is stronger π-π when solid-state interact, there is good fluorescence property, directly can be used as luminescent material, can be used for detecting metal ion according to the fluorescence property of its metal complexes analytical chemistry Rigen, also can be used for synthesizing the metal complexes that can be used as new organic luminescent device with excellent properties; Along with the development of crystal engineering, there are larger conjugate planes and be also used as eutectic synthon and metal complexes part containing the acridine compound of nitrogen-atoms.
The core of the synthesis of acridine compound is the introducing of middle pyridine ring, and a kind of method take quinoline compound as raw material, synthesis phenyl ring, and synthetic method conventional is in addition with pyridine ring in the middle of different Material synthesis.Adopt retrosynthetic analysis method, the different routes of Acridine derivatives synthesis can be obtained, as shown in figure.The method being usually used in synthesizing acridine compound mainly contains: react (shown in Fig. 1 route IA) with the Unmann that the anthranilic acid replaced and pimelinketone are raw material; With the reaction of o-Cyanoaniline and pimelinketone (shown in Fig. 1 route IA); Be raw material with o-Aminobenzaldehyde and carbonyl compound
method (shown in Fig. 1 route IB); React (shown in Fig. 1 route II) with the Bernthsen that aromatic acid or lipid acid and pentanoic are raw material; With the Corad-Limpach-Knorr method (shown in Fig. 1 route III) that arylamine and 1,3-dicarbapentaborane are raw material; And with the Pfitzinger method that the amino arone of neighbour and carbonyl compound are raw material.Most methods needs very harsh reaction conditions, as high temperature, strong acid, highly basic etc., thus limits its application.Therefore develop the synthetic method of function acridine compound that suitability, environmental friendliness, reaction conditions gentleness are extensively synthesized in new having, have great importance.
Summary of the invention
The invention provides at ZnCl
2the new synthetic method of the lower adjacent aryl amine Schiff 's base generation intramolecular cyclization synthesis acridine derivatives of effect.Reaction conditions is gentle, simple to operate, can the synthesis acridine derivatives of high yield.
The present invention with the arylamine of o fluorobenzaldehyde and at least one ortho position unsubstituted for raw material, synthesize a series of adjacent aryl amine Schiff 's base, and then develop one have broad applicability, reaction temperature and, the new synthetic method of Acridine derivatives simple to operate, to having broad application prospects in the researchs such as materials chemistry, pharmaceutical synthesis chemistry and crystal engineering.
A technical scheme of the synthetic method of acridine derivatives of the present invention is as follows.
A synthetic method for acridine derivatives is the ZnCl of 0.5 ~ 10: 1 with mol ratio
2be reactant with adjacent aryl amine Schiff 's base, reactant joined in tetrahydrofuran (THF), react 10 ~ 24 hours at 50 ~ 80 DEG C; Decompression pumps tetrahydrofuran (THF), and resistates volume ratio is methylene dichloride and the water mixed liquid process of 1: 1, separatory, aqueous phase dichloromethane extraction, merges organic phase; Decompression pumps solvent, and column chromatography for separation obtains acridine derivatives;
Described adjacent aryl amine Schiff 's base is N-(2-(phenyl amino) benzylidene) aniline, N-(2-(p-methylphenyl be amino) benzylidene) para-totuidine, N-(2-(p-methoxyphenyl be amino) benzylidene) to chlorphenylamino between methyl oxyaniline, N-(2-() benzylidene) m-chloro aniline, N-(2-(p-methylphenyl be amino) benzylidene) para-totuidine or N-(2-(p-methoxyphenyl amino) benzylidene) P-nethoxyaniline.
After reactant is joined tetrahydrofuran (THF), preferred reaction conditions reacts 24 hours at 80 DEG C.
Described ZnCl
2with the mol ratio of adjacent aryl amine Schiff 's base, preferably 0.5 ~ 2: 1.
The consumption of tetrahydrofuran (THF) can be 10 ~ 20mL/mmol by the molar amount of adjacent aryl amine Schiff 's base.
In the methods described above, preparation is phenyl ring has substituent acridine.That is, an acridine derivatives, is replace acridine, has structure as follows:
Wherein, R
1, R
2, R
3, R
4being the substituting group on phenyl ring, is hydrogen, methyl, sec.-propyl, methoxyl group, phenyl, benzyl, fluorine, chlorine, bromine etc.
Preferred phenyl ring has substituent acridine as follows:
R
1=R
2=R
3=R
4=H, acridine;
R
1=R
3=R
4=H, R
2=Me, 2-methylacridine;
R
1=R
2=R
4=H, R
3=Cl, 3-chloro-acridine;
R
1=R
2=R
3=H, R
4=Me, 4-methylacridine;
R
1=R
3=R
4=H, R
2=OMe, 2-methoxyacridine; Or
R
1=R
2=R
3=H, R
4=OMe, 4-methoxyacridine.
At ZnCl
2the new synthetic method of the adjacent aryl amine Schiff 's base intramolecular cyclization synthesis acridine derivatives under participating in, its synthetic route is as follows:
Another technical scheme of the synthetic method of acridine derivatives of the present invention is as follows.
A synthetic method for acridine derivatives, has the adjacent aryl amine Schiff 's base of preparation, synthesis acridine derivatives two steps;
The adjacent aryl amine Schiff 's base of described preparation, by the o fluorobenzaldehyde of mol ratio 1: 1: 0.225,2,6-xylidine and anhydrous magnesium sulfate add in solvent hexane, stir 2 hours, reaction mixture filters, solvent under reduced pressure is drained, underpressure distillation obtains o fluorobenzaldehyde contracting 2,6-xylidine Schiff 's base; At – 78 DEG C, the hexane solution of butyllithium is joined 1, in the tetrahydrofuran solution of 5-dinaphthylamine, be heated to room temperature, react 8 ~ 12 hours, the amine lithium salt solution obtained is transferred to o fluorobenzaldehyde contracting 2, in the tetrahydrofuran solution of 6-xylidine Schiff 's base, at room temperature react 24 hours, wherein butyllithium, 1, the mol ratio of 5-dinaphthylamine and o fluorobenzaldehyde contracting 2,6-xylidine Schiff 's base is 1: 1: 1; Reactant goes out through shrend, and the lower evaporate to dryness of organic phase decompression obtains thick product; The methanol solution of thick product, at – 15 DEG C of recrystallizations, separates out N-(2-(1,5-diamino naphthyl) benzylidene)-2,6-xylidines;
Described synthesis acridine derivatives is at ambient temperature, by equimolar ZnCl
2and N-(2-(1,5-diamino naphthyl) benzylidene)-2,6-xylidines join in tetrahydrofuran (THF), react 24 hours in the oil bath of 80 DEG C; Revolve and steam removing tetrahydrofuran (THF), resistates isopyknic methylene dichloride and water mixed liquid process, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains the amino benzacridine (polycyclic acridine derivative) replaced.
The consumption of tetrahydrofuran (THF) can by N-(2-(1,5-diamino naphthyl) benzylidene) molar amount of-2,6-xylidines is 10 ~ 20mL/mmol.
In above-mentioned novel method, also can prepare other polycyclic acridine derivative.Described polycyclic acridine derivative, is the benzacridine that amido replaces, has structure as follows:
Wherein, R
1, R
2being the substituting group on the N-atom of Aromatic Amines, is hydrogen, methyl, ethyl, sec.-propyl, phenyl, benzyl etc.
The benzacridine that preferred amido replaces is benzo (c) acridine (substituting group is hydrogen) that amino replaces.
3rd technical scheme of the synthetic method of acridine derivatives of the present invention is as follows.
A synthetic method for acridine derivatives, has the adjacent aryl amine Schiff 's base of preparation, synthesis acridine derivatives two steps;
The adjacent aryl amine Schiff 's base of described preparation, by the o fluorobenzaldehyde of mol ratio 1: 1: 0.225,2,6-xylidine and anhydrous magnesium sulfate add in solvent hexane, stir 2 hours, reaction mixture filters, solvent under reduced pressure is drained, underpressure distillation obtains o fluorobenzaldehyde contracting 2,6-xylidine Schiff 's base; At – 78 DEG C, the hexane solution of butyllithium is joined 1, in the tetrahydrofuran solution of 5-dinaphthylamine, be heated to room temperature, react 8 ~ 12 hours, the diamine lithium salt solution obtained is transferred to o fluorobenzaldehyde contracting 2, in the tetrahydrofuran solution of 6-xylidine Schiff 's base, at room temperature react 24 hours, wherein butyllithium, 1, the mol ratio of 5-dinaphthylamine and o fluorobenzaldehyde contracting 2,6-xylidine Schiff 's base is 1: 0.5: 1; Reactant goes out through shrend, and the lower evaporate to dryness of organic phase decompression obtains thick product; Methanol solution – 15 DEG C of recrystallizations of thick product, separate out N, N'-(2-(2,6-dimethyl benzene formimino) phenyl)-1,5-dinaphthylamine;
Described synthesis acridine derivatives is at ambient temperature, incites somebody to action the ZnCl of in molar ratio 4: 1
2and N, N'-(2-(2,6-dimethyl benzene formimino) phenyl)-1,5-dinaphthylamine joins in tetrahydrofuran (THF), reaction solution is placed in the oil bath reaction 24 hours of 80 DEG C; Revolve and steam removing tetrahydrofuran (THF), resistates isopyknic methylene dichloride and water mixed liquid process, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains acridine also [4,3-c] acridine (polycyclic acridine derivative).
The consumption of tetrahydrofuran (THF) can by N, N'-(2-(2,6-dimethyl benzene formimino) phenyl) molar amount of-1,5-dinaphthylamine is 15 ~ 25mL/mmol.
In above-mentioned novel method, preparation be the polycyclic acridine derivative with larger conjugated system.Described polycyclic acridine derivative, be acridine also [4,3-c] acridine, its structure is as follows:
Acridine compound is the important heteroaromatic compound of a class, due to its wide region performance and widely purposes attracted the broad interest of people.Such as most of acridine compound all has biological activity, can be used for antibacterial, antimalarial, anticancer etc.; And acridine ring has larger conjugate planes, there is good fluorescence property, can be used as luminescent material.In addition, the acridine compound with larger conjugate planes is also used as eutectic synthon, metal complexes part in crystal engineering field.
Raw material of the present invention is common industrial chemicals, and reaction solvent is tetrahydrofuran (THF), and the retortable recycling of solvent, be convenient to reduce costs; Temperature of reaction is 50 ~ 80 degree, and reaction conditions is gentle, environmental friendliness; Post-reaction treatment is simple, and reaction conversion ratio up to 99%, can have and extensively synthesize suitability, is convenient to large-scale synthesis.Many ring functions acridine derivatives synthesized by the inventive method is the heteroaromatic compound that a class has significant application value, has broad application prospects in fields such as Materials science, pharmaceutical synthesis chemistry and crystal engineerings.
Accompanying drawing explanation
Fig. 1 is the acridine retrosynthetic analysis schematic diagram in Acridine derivatives.
Embodiment
Column chromatography in following each embodiment, stationary phase is silica gel, and moving phase (eluent) is sherwood oil and ethyl acetate; Under normal pressure, flow velocity is 1 ~ 3 drop/sec.
The synthesis of embodiment 1 acridine
At ambient temperature, by the ZnCl of 0.4mmol
2, 0.2mmol joins in the tetrahydrofuran (THF) of 2mL, and oil bath reaction solution being placed in 80 DEG C is reacted 24 hours.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains white solid acridine, productive rate 99%.
1H NMR(300MHz,CDCl
3,298K):δ7.55(m,2H,Ar-H),7.80(m,2H,Ar-H),8.02(d,J=6.0Hz,2H,Ar-H),8.25(d,J=9.0Hz,2H,Ar-H),8.80(s,1H,Ar
N-H)ppm。
In the synthetic method (sequence number 7 namely in table 1) of the above-mentioned acridine derivatives of embodiment 1, change ZnCl
2with N-(2-(phenyl amino) benzylidene) aniline mol ratio, change reaction solvent, temperature of reaction, reaction times, also can synthesize white solid acridine, but productive rate declines to some extent or productive rate is too low.Concrete reaction conditions and in the productive rate of Schiff 's base in table 1.
When reaction solvent is trichloromethane, the productive rate of acridine is too low, and when reaction solvent is tetrahydrofuran (THF), productive rate is higher, and therefore the preferred tetrahydrofuran (THF) of the present invention is reaction solvent.If temperature of reaction is lower than 50 DEG C, productive rate also can be caused too low.
Table 1 shows, preferred temperature of reaction is 80 DEG C, the reaction times is 24 hours.
Under preferred synthesis condition, along with ZnCl
2the increase of consumption, can increase in the productive rate of Schiff 's base.Work as ZnCl
2with N-(2-(phenyl amino) benzylidene) mol ratio of aniline is when being greater than 10, also can increase in the productive rate of Schiff 's base, but the obvious step-down of amplitude increased, can ZnCl be caused thus
2waste.Experiment shows, preferred ZnCl
2with N-(2-(phenyl amino) benzylidene) mol ratio of aniline is 0.5 ~ 2: 1.
Table 1
To following embodiment 2 ~ 6, change ZnCl2 and N-(2-(phenyl amino) benzylidene) mol ratio of aniline, change reaction solvent, temperature of reaction, the reaction times, test-results and table 1 are substantially identical.
The synthesis of embodiment 2 2-methylacridine
At ambient temperature, by the ZnCl of 0.2mmol
2, the N-(2-(p-methylphenyl of 0.2mmol is amino) and benzylidene) para-totuidine joins in the tetrahydrofuran (THF) of 2mL, reaction solution is placed in the oil bath reaction 24 hours of 80 DEG C.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains light yellow solid 2-methylacridine, productive rate 76%.
1H NMR(300MHz,CDCl3,298K):δ2.59(s,2-CH3),7.54(t,1H),7.65(d,1H),7.75–7.81(m,2H),7.99(d,1H),8.21(d,1H),8.29(d,1H),8.70(s,1H,Ar
N-H)ppm。
Embodiment 3 2-methoxyacridine
At ambient temperature, by the ZnCl of 0.4mmol
2, the N-(2-(p-methoxyphenyl of 0.2mmol is amino) and benzylidene) join in the tetrahydrofuran (THF) of 2mL to methyl oxyaniline, oil bath reaction solution being placed in 80 DEG C is reacted 24 hours.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains yellow solid 2-methoxyacridine, productive rate 97%.
1H NMR(300MHz,CDCl
3,298K):δ3.99(s,3H,2-OCH
3),7.18(s,1H,1-H),7.77(t,1H),7.98(d,1H),7.54(t,1H),7.57(d,1H),8.26(d,1H),8.32(d,1H),8.69(s,1H,9-H)ppm。
The synthesis of embodiment 4 3-chloro-acridine
At ambient temperature, by the ZnCl of 0.4mmol
2, chlorphenylamino between the N-(2-(of 0.2mmol) and benzylidene) m-chloro aniline joins in the tetrahydrofuran (THF) of 2mL, reaction solution is placed in the oil bath reaction 24 hours of 80 DEG C.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains yellow solid 3-chloro-acridine, productive rate 50%.
1H NMR(300MHz,CDCl
3,298K):δ7.45(dd,J=2.1Hz,9.0Hz,1H,),7.55(dt,J=0.6Hz,7.2Hz,1H),7.81(dt,J=1.2Hz,8.1Hz,1H),7.66(d,J=9.0Hz,1H),7.91(d,J=9.0Hz,1H),7.96(d,J=8.7Hz,1H),8.23–8.27(br,2H),8.75(s,1H)ppm。
The synthesis of embodiment 5 4-methylacridine
At ambient temperature, by the ZnCl of 0.2mmol
2, the N-(2-(p-methylphenyl of 0.2mmol is amino) and benzylidene) para-totuidine joins in the tetrahydrofuran (THF) of 2mL, reaction solution is placed in the oil bath reaction 24 hours of 80 DEG C.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains yellow solid 4-methylacridine, productive rate 73%.
1H NMR(300MHz,CDCl
3,298K):δ2.96(s,3H,4-CH
3),7.43(t,1H),7.53(t,1H),7.62(d,1H),7.77(t,1H),7.84(d,1H),7.99(d,1H),8.29(d,1H),8.72(s,1H)ppm。
The synthesis of embodiment 6 4-methoxyacridine
At ambient temperature, by the ZnCl of 0.4mmol
2, the N-(2-(p-methoxyphenyl of 0.2mmol is amino) and benzylidene) P-nethoxyaniline joins in the tetrahydrofuran (THF) of 2mL, reaction solution is placed in the oil bath reaction 24 hours of 80 DEG C.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains yellow solid 4-methoxyacridine, productive rate 95%.
1H NMR(300MHz,CDCl
3,298K):δ4.50(s,OCH
3),7.43(d,J=9.0Hz,1H),7.67(t,J=7.5Hz,1H),7.77(t,J=7.5Hz,1H,Ph-H),7.86(d,J=9.0Hz,1H,Ph-H),8.07(t,J=9.0Hz,1H,Ph-H),8.18(d,J=9.0Hz,1H,Ph-H),8.43(d,J=9.0Hz,1H,Ph-H),9.17(s,1H,Ar
N-H)ppm。
The synthesis of benzo (c) acridine that embodiment 7 amino replaces
By 37mmol o fluorobenzaldehyde, 37mmol2,6-xylidine, 1g anhydrous magnesium sulfate adds in the hexane of 40mL, stirs 2 hours, and reaction mixture filters, solvent under reduced pressure is drained, and thick product obtains o fluorobenzaldehyde contracting 2,6-xylidine Schiff 's base through underpressure distillation.At – 78 DEG C, the n-buli hexane solution of 20mmol is added 1 of 20mmol, in the tetrahydrofuran solution of 5-dinaphthylamine, reaction mixture heat is to room temperature, (can be 8 ~ 12 hours) be spent the night in reaction, the amine lithium salt solution obtained is transferred to the o fluorobenzaldehyde contracting 2 of 20mmol, the tetrahydrofuran solution of 6-xylidine Schiff 's base, at room temperature react 24 hours, reactant goes out through 20mL shrend, the lower evaporate to dryness of organic phase decompression, methanol solution – 15 DEG C of recrystallizations of thick product, separate out N-(2-(1, 5-diamino naphthyl) benzylidene)-2, 6-xylidine, productive rate 52%.
Its molecular formula of ultimate analysis is C
25h
23n
3: C, 82.10; H, 6.28; N, 11.70.
At ambient temperature, by the ZnCl of 0.2mmol
2, the N-(2-(1 of 0.2mmol, 5-diamino naphthyl) and benzylidene)-2,6-xylidines join in the tetrahydrofuran (THF) of 2mL, reaction solution are placed in the oil bath reaction 24 hours of 80 DEG C.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains benzo (c) acridine that yellow solid amino replaces, productive rate 65%.
1H NMR(300MHz,CDCl
3,298K):
1H NMR(300MHz,CDCl
3,298K):δ7.14(d,J=9.0Hz,1H,Ar-H),7.32(d,J=9.0Hz,1H,Ar-H),7.51(t,J=7.5Hz,1H,Ar-H),7.65(t,J=7.5Hz,1H,Ar-H),7.88(t,J=7.5Hz,1H,Ar-H),8.13(d,J=9.0Hz,1H,Ar-H),8.22(d,J=9.0Hz,1H,Ar-H),8.45(d,J=9.0Hz,1H,Ar-H),8.90(s,1H,Ar-H),9.65(d,J=9.0Hz,1H,Ar-H)ppm。
The synthesis of embodiment 8 acridine also [4,3-c] acridine
By 37mmol o fluorobenzaldehyde, 37mmol2,6-xylidine, 1g anhydrous magnesium sulfate adds in the hexane of 40mL, stirs 2 hours, and reaction mixture filters, solvent under reduced pressure is drained, and thick product obtains o fluorobenzaldehyde contracting 2,6-xylidine Schiff 's base through underpressure distillation.At – 78 DEG C, the n-buli hexane solution of 20mmol is added 1 of 10mmol, in the tetrahydrofuran solution of 5-dinaphthylamine, reaction mixture heat is to room temperature, (can be 8 ~ 12 hours) be spent the night in reaction, the diamine lithium salt solution obtained is transferred to the o fluorobenzaldehyde contracting 2 of 20mmol, 6-xylidine Schiff 's base tetrahydrofuran solution, at room temperature react 24 hours, reactant goes out through 20mL shrend, the lower evaporate to dryness of organic phase decompression, methanol solution – 15 DEG C of recrystallizations of thick product, separate out N, N'-(2-(2, 6-dimethyl benzene formimino) phenyl)-1, 5-dinaphthylamine, productive rate 60%.
Its molecular formula of ultimate analysis is C
40h
36n
4: C, 83.56; H, 6.40; N, 9.68.
At ambient temperature, by the ZnCl of 0.4mmol
2, the N of 0.1mmol, N'-(2-(2,6-dimethyl benzene formimino) and phenyl)-1,5-dinaphthylamine joins in the tetrahydrofuran (THF) of 2mL, reaction solution is placed in the oil bath reaction 24 hours of 80 DEG C.Revolve and steam removing tetrahydrofuran (THF), the methylene dichloride of resistates 15mL and the process of 15mL water mixed liquid, separatory, aqueous phase dichloromethane extraction, merge organic phase; Removal of solvent under reduced pressure, column chromatography for separation, obtains yellow solid acridine also [4,3-c] acridine, productive rate 35%.
1H NMR(300MHz,CDCl
3,298K):δ7.63–7.68(m,2H,Ar-H),7.86–7.91(m,2H,Ar-H),8.12(d,J=9.0Hz,2H,Ar-H),8.24(d,J=9.0Hz,2H,Ar-H),8.46(d,J=9.0Hz,2H,Ar-H),8.91(s,2H,Ar-H),9.65(d,J=9.0Hz,2H,Ar-H)ppm。
Claims (1)
1. a synthetic method for acridine derivatives is the ZnCl of 2: 1 with mol ratio
2be reactant with adjacent aryl amine Schiff 's base, reactant joined in tetrahydrofuran (THF), react 24 hours at 80 DEG C; Decompression pumps tetrahydrofuran (THF), and resistates volume ratio is methylene dichloride and the water mixed liquid process of 1: 1, separatory, aqueous phase dichloromethane extraction, merges organic phase; Decompression pumps solvent, and column chromatography for separation obtains acridine derivatives; Described adjacent aryl amine Schiff 's base is that N-(2-(phenyl amino) benzylidene) aniline or N-(2-(p-methoxyphenyl is amino) benzylidene) are to methyl oxyaniline.
Priority Applications (1)
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| Regioselective cyclisation of anil derivatives-A short synthesis of dibenzacridines;Gandi K Kar等;《Tetrahedron Letters》;19891231;第30卷(第2期);第223－224页 * |
| 含2,4-二甲基-7-氨基喹啉西佛碱Zn(II)配合物的合成、表征及发光性能的研究;苏清;《中国博士学位论文全文数据库工程科技I辑》;20070915;第76－79、107－108页 * |
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