CN1824660A

CN1824660A - Benzopyran kind compound and its preparation method

Info

Publication number: CN1824660A
Application number: CN 200510009539
Authority: CN
Inventors: 陈拥军; 吴彦超; 刘利; 王东
Original assignee: Institute of Chemistry CAS
Current assignee: Institute of Chemistry CAS
Priority date: 2005-02-21
Filing date: 2005-02-21
Publication date: 2006-08-30
Anticipated expiration: 2025-02-21
Also published as: CN100434427C

Abstract

The present invention relates to a benzopyran compound and its preparation method. Said preparation method includes the following steps: making phenol compound and alpha, beta-unsaturated ketone or beta, gamma-unsaturated ketene ester compound undergo the process of reflux reaction for 1-3 days in organic acid, their material-adding ratio is 1:2, after the reaction is completed, trifluoroacetic acid can be distilled out and reused, the residue can be dissolved in organic solvent of dichloromethane, washing by using saturated sodium hydrogen carbonate aqueous solution, drying by using drying agent of anhydrous sodium sulfate, filtering, desolventizing and column chromatography so as to obtain the invented product benzopyran compound.

Description

A kind of benzopyrans compounds and preparation method

Technical field

The present invention relates to a kind of benzopyrans compounds.

The invention still further relates to the preparation method of above-claimed cpd.

Background technology

The chromene heterogeneous ring compound is widely used in synthesis of natural product, functional materials and biomedical research.For example, 2-aryl-2-hydroxyl-benzopyrans compounds and natural cyanidin(e) have quite similar structure, have similar character, are potential natural flowers pigment surrogate, food colorant and biologically active substance.This compounds is (acid-basicity under multiple ambient conditions, temperature, light), can present multiple ad hoc structure form, be applicable to the information processing system on the molecular level, quite paid close attention in recent years aspect optics memory and the logical switch (J. Am.Chem.Soc.2003,125,987-994).Benzopyrans compounds is the important intermediate of multiple natural product and medicine.The benzopyrans compounds of having found has multiple pharmaceutical activity, as sterilization, anticancer, antiulcer agent, tuberculosis isoreactivity.Benzopyrans compounds is applied to a kind of novel potassium-channel activator, more and more causes medicine scholar's interest in recent years.This compounds is applied to the big interest that novel target enzyme also is the medicine scholar, as be applied to hiv reverse transcriptase inhibitor etc. (J. Am.Chem.Soc.2000,122,9939-9953).Find, novel chromene heterogeneous ring compound and the synthetic method thereof of development will be to them in pharmaceutical chemistry, the applied research in biomedicine and the Materials science has important promoter action.

Use because heterogeneous ring compounds such as chromene have widely, formed some synthetic methods (J.Am.Chem.Soc.1943,65,2135 for many years; J. Am.Chem.Soc.1998,120,2343-2351; Org.Lett.2000,2,4063-4065; Org.Lett.2002,4,3679-3681; Org.Lett.2003,5,1055-1058 etc.), still very important but development can synthesize (as 2,2-disubstituted benzene and pyrans), the novel and effective chromene synthetic method of specific replacement.For 2-aryl-2-hydroxyl-benzopyrans compounds with cyanidin(e) character, because it is comparatively responsive to acid-basicity, temperature and light, do not have effective synthetic method for many years, but synthetic its another kind of existence form-benzopyralium salt.The synthetic method of benzopyralium salt mainly is to get with very active substrate such as diphenol or triphenol etc. and 1,3 cyclohexadione compounds or its Equivalent condensation; In addition, also can obtain (J.Chem.Soc.1952,4957-4959 with reactions such as flavones or flavonoid class compound and grignard reagents; Can.J.Chem.2001,79,1173-1178 etc.).These methods have limitation mostly, need very active substrate or need multistep synthetic.Therefore be necessary to develop the new synthetic method of the benzopyran compounds of highly effective, also provide relevant strategy simultaneously for other similar heterogeneous ring compound synthetic.

Summary of the invention

The object of the invention is to provide a kind of benzopyrans compounds.

Another purpose of the present invention is to provide a kind of method for preparing above-claimed cpd.

For achieving the above object, benzopyrans compounds structure provided by the invention as shown in the formula

In the formula: X is hydrogen atom, alkyl (as the methyl and the tertiary butyl), aryl (as phenyl), methoxyl group, halogen (as fluorine, chlorine and bromine) etc.; Ar ¹Be the aryl that does not replace or replace; Ar ²Be aryl or the CO that does not replace or replace ₂R, R are alkyl such as methyl, ethyl etc.Work as Ar ²Be CO ₂During R, product is the chromene ester compound.

Preparation method provided by the invention, key step is:

With phenolic compound (as phenol, naphthols etc.) and alpha, beta-unsaturated ketone or beta, gamma-ethylenic unsaturation ketone ester compounds in organic acid back flow reaction 1-3 days, feed ratio is 1: 2, after reaction finished, trifluoroacetic acid can steam repeated use, and residuum is through organic solvent dissolutions such as methylene dichloride, the saturated sodium bicarbonate aqueous solution washing, siccative dryings such as anhydrous sodium sulphate are filtered precipitation, silica gel column chromatography separates, and obtains benzopyrans compounds.

The alpha, beta-unsaturated ketone compounds that the present invention adopts is as replacing or do not replace cinnamophenone.

Beta, gamma-ethylenic unsaturation ketone ester compounds such as γ-aryl-beta, gamma-ethylenic unsaturation keto acid ethyl ester or methyl esters that the present invention adopts.

Organic acid such as trifluoroacetic acid or formic acid etc. that the present invention adopts, its add-on is 30 times of phenol weight.

The used eluent of silica gel column chromatography of the present invention is sherwood oil and ethyl acetate (sherwood oil: ethyl acetate=20: 1 to 3: 1 volume ratios).

The productive rate of the target product that the present invention obtains after separating purification is at 50-85%.The gained compound through nmr spectrum ( ¹H-NMR and ¹³C-NMR), mass spectrum (MS), infrared spectra (IR) conclusive evidence, high resolution or ultimate analysis determine to also have a plurality of X-ray crystal structure to resolve, structure is errorless.

The raw material ratio that adopts is easier to buy or is synthetic, and chalcone compounds has multiple synthetic method, and as document (J.Am.Chem.Soc.1952,74,4397) report is exactly a kind of feasible method; Beta, gamma-ethylenic unsaturation ketone ester can by document (J.Am.Chem.Soc.1952,74,4392. and J.Org.Chem.2000,65,4487-4497) the report method is synthetic.

In addition, because such reaction is fit to multiple reaction substrate,, can synthesize the abundant multiple heterogeneous ring compound of structure through the too much optimization or the adjusting of reaction substrate.Because the compound that synthesizes can have a plurality of active functional groups, can further derive, be expected in the active compound of synthesis of natural product, functional materials, biologically active or potential source biomolecule, be used widely to multiple functional compounds such as novel a-amino acid and α-An Jisuanzhi.

Embodiment

Embodiment 1 (chromene ester):

Its reaction process as shown in the formula

In the above-mentioned reaction formula: X is hydrogen atom, alkyl (as the methyl and the tertiary butyl), aryl (as phenyl), methoxyl group, halogen (as fluorine, chlorine and bromine) etc.; Ar is the aryl that does not replace or replace; R is alkyl such as methyl, ethyl etc.

Concrete preparation method is:

0.2 mole of p-tert-butylphenol and 0.4 mole of beta-phenyl-beta, gamma-ethylenic unsaturation keto acid ethyl ester are added in 2 milliliters of trifluoroacetic acids.Back flow reaction 2 days steams trifluoroacetic acid in order to using next time again.The residuum residuum dissolves with 10 milliliters of methylene dichloride, 5 milliliters of saturated sodium bicarbonate aqueous solution washings, anhydrous sodium sulfate drying, filter decompression precipitation, column chromatography (sherwood oil: ethyl acetate=5: 1), obtain 2-hydroxyl-2-ethoxycarbonyl 4-phenyl-6-tertiary butyl benzo pyrans, yield 73.0%; The clear crystal shape; Fusing point 115-116 ℃; Nucleus magnetic hydrogen spectrum ( ¹HNMR, 400MHz, CDCl ₃) 7.45-7.41 (m, 5H), 7.31 (dd, J=8.51,2.40Hz, 1H), 7.21 (d, J=2.38Hz, 1H), 7.00 (d, J=8.48Hz, 1H), 5.84 (s, 1H), 4.44 (s, 1H), 3.88 (s, 1H), 1.21 (s, 9H); Nuclear-magnetism carbon spectrum ( ¹³C NMR, 100MHz, CDCl ₃) 169.78,148.17,144.62,139.44,137.15,128.79,128.37,128.32,126.95,123.12,119.27,116.95,116.38,93.26,53.70,34.26,31.34; Infrared spectra 3467,2960,1743,1489,1287,1236,1149,1026,768,698cm ^-1High resolution (M+Na) ⁺C ₂₁H ₂₂NaO ₄: 361.1410, Found:361.1407; Ultimate analysis theoretical value: C, 74.54; H, 6.55. measured value: C, 74.77; H, 6.74; Resolve through the X-ray crystal structure.

Embodiment 2 (anthocyan compound)

Its reaction process as shown in the formula

In the formula: X is hydrogen atom, alkyl (as the methyl and the tertiary butyl), aryl (as phenyl), methoxyl group, halogen (as fluorine, chlorine and bromine) etc.; Ar ¹Be the aryl that does not replace or replace; Ar ²Be the aryl that does not replace or replace.

Concrete preparation method is:

0.2 mole of p-tert-butylphenol and 0.4 mole of 4-chlorine cinnamophenone are added in 2 milliliters of trifluoroacetic acids, and back flow reaction 3 days steams trifluoroacetic acid in order to using next time again; Residuum dissolves with 10 milliliters of methylene dichloride, 5 milliliters of saturated sodium bicarbonate aqueous solution washings, anhydrous sodium sulfate drying, filter, decompression precipitation (temperature is no more than 40 degree), column chromatography (sherwood oil: ethyl acetate=15: 1), obtain 2-hydroxyl-2-phenyl-4-rubigan-6-tertiary butyl benzo pyrans, yield 73.0%; Spumescence; Nucleus magnetic hydrogen spectrum ( ¹H NMR, 300MHz, CDCl ₃) 7.71 (dd, J=7.80,1.12Hz, 2H), 7.44-7.33 (m, 8H), 7.19 (d, J=2.28Hz, 1H), 7.09 (d, J=8.48Hz, 1H), 5.86 (s, 1H), 3.25 (s, 1H), 1.25 (s, 9H); Nuclear-magnetism carbon spectrum ( ¹³C NMR, 75MHz, CDCl ₃) 149.21,144.43,143.11,136.13,135.91,134.16,130.18,128.67,128.59,128.40,127.17,125.81,124.18,122.66,119.15,117.01,96.54,34.37,31.47; Infrared spectra 3407,3035,2961,1489,1258,1088,1015,825,763,699cm ^-1Ultimate analysis theoretical value: C, 76.81; H, 5.93. measured value: C, 76.35; H, 6.37.Also obtain 4-chlorine dihydrochalcone simultaneously, yield 70.0%, white solid; Fusing point 53-54 ℃; Nucleus magnetic hydrogen spectrum ( ¹HNMR, 300MHz, CDCl ₃) 7.94 (dd, J=8.52,1.11Hz, 2H), 7.58-7.42 (m, 3H), 7.25 (d, J=8.46Hz, 2H), 7.18 (dd, J=8.33Hz, 2H), 3.28 (t, J=7.58Hz, 2H), 3.04 (t, J=7.45Hz, 2H); Nuclear-magnetism carbon spectrum ( ¹³C NMR, 75MHz, CDCl ₃) 198.85,139.76,136.75,133.19,131.87,129.85,128.66,128.61,128.03,40.15,29.38; Infrared spectra 3034,2925,1669,1490,825,774,686cm ^-1Ultimate analysis theoretical value: C, 73.62; H, 5.35. measured value: C, 73.64; H, 5.38.

Claims

1. benzopyrans compounds, structure as shown in the formula

In the formula: X is hydrogen atom, alkyl, aryl, methoxyl group or halogen;

Ar ¹Be the aryl that does not replace or replace;

Ar ²Be aryl or the CO that does not replace or replace ₂R, wherein R is an alkyl.

2. prepare the method for claim 1 compound, key step is:

A) with phenolic compound and alpha, beta-unsaturated ketone or beta, gamma-ethylenic unsaturation ketone ester compounds with 1: 2 mol ratio in organic acid back flow reaction 1-3 days;

B) steam organic acid, the reactant organic solvent dissolution, the saturated sodium bicarbonate aqueous solution washing, the siccative drying is filtered precipitation below 40 ℃;

C) silica gel column chromatography separates, and the volume ratio of eluent is a sherwood oil: ethyl acetate=20: 1-3: 1, obtain benzopyrans compounds;

Described phenolic compound is phenol or naphthols;

Described alpha, beta-unsaturated ketone compounds is for replacing or do not replace cinnamophenone;

Described beta, gamma-ethylenic unsaturation ketone ester compounds is γ-aryl-beta, gamma-ethylenic unsaturation keto acid ethyl ester or methyl esters;

Described organic acid is trifluoroacetic acid or formic acid, and its add-on is 30 times of phenol weight;

Described organic solvent is a methylene dichloride.

3. the method for claim 2 is characterized in that, the organic acid that step b steams is reused.