UA150472U - Process for preparing substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4h-chromen-4-ones - Google Patents

Abstract

A process for preparing substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones of general formula I , wherein R = H, OH, OCH2C6H5, R1 = H, OCH2C6H5, which involves the condensation reaction of substituted acetophenone and substituted aldehyde in organic solvent at a given temperature in the presence of catalyst, the reaction of oxidative heterocyclization of unsaturated ketone in organic solvent the presence of a catalyst and an oxidant, the reaction of removing the protecting group (debenzylation) of the obtained benzyl derivative of chromene-4-one 2 up to obtaining the corresponding derivative of 7,3',4'-flavon-3-ol in organic solvent in the presence of a catalyst. The condensation reaction is carried out for 6 hours, 2-hydroxyacetophenone or 2-hydroxy-4-benzyloxyacetophenon is used as a substituted acetophenone, 3,4-dibenzyloxybenzaldehyde – as a aldehyde in equal molar amount, sodium hydroxide – as a catalyst. The condensation reaction is carried out in a solvent of ethanol at 50 oC to obtain 3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one або 3-(3,4- dibenzyloxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one. The oxidative heterocyclization reaction is carried out for 40 min, 3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one або 3-(3,4- dibenzyloxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one is used as a unsaturated ketone, ethanol is used as a solvent, aqueous solution (50%)of sodium hydroxide – as a catalyst, 25% aqueous solution of hydrogen peroxide – as a oxidant, up to obtaining 2-(3,4- dibenzyloxyphenyl)-3-hydroxy-4H-chromene-4-one або 2-(3,4,7- tribenzyloxyphenyl)-3-hydroxy-4H- chromene-4-one. The removing of protective group (debenzylation) is carried out in a solvent such as ethanol-aceiktytic acid (5:1) at a room temperature, 2-(3,4- dibenzyloxyphenyl)-3-hydroxy-4H-chromene-4-one або 2-(3,4,7- tribenzyloxyphenyl)-3-hydroxy-4H- chromene-4-one is used as a benzyl derivative, plladium on carbon (10% palladium) – as a catalyst, the concentration of the catalywst in the reaction mixture is 1% by weight, to obtain final product - 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-trihydroxyphenyl)-3-hydroxy-4H-chromen-4-one.

Description

chromen-4-one or 2-(3,4,7-tribenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one, as a catalyst - palladium on carbon (10 95 palladium), the concentration of the catalyst in the reaction mixture is 1 95 masses; to the formation of the final product - 2-(3,4-hydroxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-trihydroxyphenyl)-3-hydroxy-4H-chromen-4-one .

The useful model belongs to the field of organic chemistry, in particular, to the method of obtaining substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones of the general formula I

Ov, v o F on (v) where K - H, OH, OSNoSeH5,V'-H, OSNeSenNv5,

Flavonoids are well-known natural substances - secondary metabolites of plants and fungi. These compounds have significant antioxidant, cancerostatic, anti-inflammatory and P-vitamin properties, due to which they are widely used in medicine | Vose, 5., zZagkKag, 0.,

Voze, A., Mapaa!), 5.S0b., Rpapta Yunehu. 2013, 61-75 (2018)). In addition, some flavonoids are metallochromes and metallofluorochromes, so they are quite often used in analytical chemistry as indicators for metal ions in non-aqueous solutions and in mixed media. (By. Vizpor E.|. Ohio-Mem Mogk-Togopio: Regdatop Rgev5, 496 (1972)|.

Substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones can be used as indicators of acidity and hydration |Msto!tomu, O., Kazypa, M., Ateg. boss. Tevzi Maieg., 16-25 (1985)), as well as as metallofluorophoric indicators for non-aqueous environments |Ipaisatsog5. Geai.

Vizpor E.I). Okhtoga-Mem/ MogKk-Togopio: Regdatop Rgezv, 496 (1972)|.

A known method of obtaining substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones -

AND! he no (c) F on

AND! he (c) is described in TsKuka T5ipeKazha, Kepdo Napaua, Zpiypei Nidazpirauavhpi, TakKev5pi zidai,

Viozsiepse, Vioyespppoiodu, apa Viospetivzigu, 82, 8, Z A!ydivi 2018, 1316-1322(2018), roGoga/10.1080/09168451.2018.14672631. (in)

With it (c) (c) (c) RADON) S

Z o NAvBM NO o - iz on o A. Still (c) (c) on (c) (c) (c) A. sh o on o

HER

The method of synthesis of quercetin (2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one) is three-stage. In the first two stages, such toxic compounds as methanol and tetrahydrofuran are used as solvents. And in the third stage, the final product was obtained by removing protective acetyl groups with sodium dithionite in a solvent mixture of water and methanol in the presence of sodium hydroxide for 4 hours at room temperature. The product is purified by column chromatography. The total yield of the final product is 32 95. The total reaction time is 38 hours.

The disadvantage of the known production method is the use of toxic solvents - methanol and tetrahydrofuran. The product that can be obtained by this method is not pure enough and requires additional purification by chromatographic methods, which take a lot of time and resources.

Another known method of obtaining substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones - I, on on no c) F

More | he no he (c)

AI is described in ISpiaga Vogzagi, Kozagia I isiapi, Sesia Rosi, 9). May Spent 59, 16, 7598-7616 (2016), BOI: 10.1021 /as5.|Itedsneti.

Osn» on osn, F on no (o) one (in) F VV», СНоСИ, on baths no on on on on (o) o Sho.

The method is three-stage. At the first stage, the corresponding aldehyde and ketone are introduced into the reaction in ethanol, the catalyst is sodium hydroxide, yields 21-48 95.

The reaction time at the first stage is approximately 12 hours.

At the second stage, the solution of the corresponding unsaturated ketone is introduced into the heterocyclization reaction in the presence of sodium hydroxide, hydrogen peroxide at room temperature, yields 25-81 95.

In the third stage, the intermediate product is treated in dry dichloromethane with boron tribromide at a temperature of about 0 "C. The yield is not specified.

The total yield of the final product is not specified. The total reaction time is 28 hours.

The disadvantage of the known method is the use of a toxic solvent - dichloromethane and a highly toxic reagent - boron tribromide.

Carrying out the reaction at low temperatures (about 0 C) requires special equipment (ice generator). The need to use dried solvents should also be attributed to the significant disadvantages of the known method of obtaining compounds of formula I, since drying and subsequent rectification of solvents takes a lot of time and significantly increases the duration of the synthesis.

Another known method of obtaining substituted 2-(3,4-dihydroxy-phenyl)-3-hydroxy-4H-chromen-4-ones is IM, on (c) F

More | he he

Ge) IM is described in (Egedegidne A. A. map Askeg, shUo5 A. Nadetap, Scido K. M. M. Naepep, Umit U. RE. map deg Miidn, Aaiyi Vazi, apa Migo M. R. V. Mepade, in). Honey. Spet., 43, 3752-3760 (2000).

yes and (in) 8 Zh

Ge) Ra/S, N. he sa to

Fi i on

Ge) IM (c)

This method of synthesis is also three-stage. In the first and second stages, condensation and cyclocondensation reactions are used, which lead to obtaining the corresponding dibenzyloxy derivative of chromen-4-one. Removal of benzylic protective groups is carried out by reduction in a hydrogen atmosphere in the presence of a catalyst - palladium hydroxide at room temperature. Isolation and purification of the final product was carried out by extraction with dichloromethane and subsequent recrystallization from methanol.

The total reaction time is 52 hours. The total output is 35 95 from the theory.

Disadvantages of this method include the use of a cumbersome and time-consuming separation method - extraction, toxic solvents - methanol and dichloromethane, as well as expensive and difficult to regenerate palladium hydroxide.

The third of the given analogues was chosen as the closest analogue.

The basis of a useful model is the task of developing a method of substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones, which allows to increase the yield and quality of the final product without the use of flammable, explosive and toxic solvents.

The problem is solved by the fact that in the method of obtaining substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones of the general formula I

Ov, Vch

СО on (c) where K - H, OH, OSNoSenH5, B'-H, OSNeSenNv, in which the condensation reaction of substituted acetophenone and substituted aldehyde is carried out in an organic solvent at a given temperature in the presence of a catalyst, after which the reaction of oxidative heterocyclization of an unsaturated ketone in in an organic solvent in the presence of a catalyst and an oxidizing agent, followed by a reaction of removal of the protective group (debenzylation) of the obtained benzyl derivative chromen-4-one 2 to the corresponding derivative 7,3 4y-flavon-3-ol in an organic solvent in the presence of a catalyst, according to a useful model , the condensation reaction is carried out for b hours, 2-hydroxyacetophenone or 2-hydroxy-4-benzyloxyacetophenone is used as substituted acetophenone, as aldehyde - 3,4-dibenzyloxybenzaldehyde in equimolar amounts, as catalyst - sodium hydroxide; the condensation reaction is carried out in the solvent ethanol at 50"C until the formation of 3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one or 3-(3,4-dibenzyloxyphenyl)-1 -(2,4-dihydroxyphenyl)prop-2-en-1-one; the oxidative heterocyclization reaction is carried out for 40 minutes, using /3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop- 2-en-1-one or 3-(3,4-dibenzyloxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one, ethanol is used as a solvent, and an aqueous solution is used as a catalyst (50 95 ) sodium hydroxide as an oxidizing agent 25595 aqueous solution of hydrogen peroxide, to the formation of 2-(3,4-dibenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-tribenzyloxyphenyl)-3- hydroxy-4H-chromen-4-one; the reaction of removing the protective group (debenzylation) is carried out in the solvent ethanol-acetic acid (5:1) at room temperature, as a benzyl derivative, 2-(3,4-dibenzyloxyphenyl)-3-hydroxy- 4H-chromen-4-one or 2-(3,4,7-tribenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one as catal catalyst - palladium on carbon (10 95 palladium), the concentration of the catalyst in the reaction mixture is 190 by mass; to the formation of the final product - 2-(3,4-hydroxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-trihydroxyphenyl)-3-hydroxy-4H-chromen-4-one .

The method of obtaining substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones includes three synthetic stages. 19) Her (in) ov Ov

B --2 -- - 5 2 l'25K maon maon, EON

Kk on Ov, in on Ov,

And in the village

Ow, Ow,

In solo ZHI

Ov, nura Ov,

EUN, he snsoon he (c) (c) r E

KAN, OH, OSNoSnH5, NI-H, OSNeSenH in,

The first stage is the interaction of the corresponding substituted hydroxyacetophenone (A) and substituted aldehyde (B) in an organic solvent at a given temperature in the presence of a catalyst during the time required for the formation of product (C), according to a useful model, the reaction is carried out for 6 hours, as 2-hydroxyadetophenone or 2-hydroxy-4-benzyloxyacetophenone is used for substituted acetophenone, 3,4-dibenzyloxybenzaldehyde in equimolar amounts as an aldehyde, and sodium hydroxide as a catalyst; the condensation reaction is carried out in the solvent ethanol at 50 "C until the formation of an intermediate product - an unsaturated ketone - 3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one or 3-(3, 4-dibenzyloxyphenyl)-1-(2,4-dihydroxyphenyl)-prop-2-en-1-one.

The second stage - includes the oxidative heterocyclization of the original unsaturated ketone (C) in an organic solvent at the appropriate temperature in the presence of a catalyst during the time required for the formation of the product (0), according to a useful model, the interaction reaction is carried out for 40 minutes, as an unsaturated ketone, 3 -(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one or 3-(3,4-dibenzyloxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-ene -1-one, as a catalyst - an aqueous solution (50 95) of sodium hydroxide, as an oxidant - 25 95 aqueous solution of hydrogen peroxide, the reaction is carried out in an ethanol solvent at a temperature of 60 "C until the formation of an intermediate product - 2-(3,4-di (benzyloxy)phenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-tri(benzyloxy)phenyl)-3-hydroxy-4H-chromen-4-one.

The third stage - includes the reduction with hydrogen (removal of the protective benzyl group) of the obtained benzyl derivative chromen-4-one (0) to the corresponding derivative 7,34"-flavon-Z-ol (E) in an organic solvent at the appropriate temperature in the presence of a catalyst over time, necessary for the formation of the product, according to a useful model, the interaction reaction is carried out

Within 24 hours, 2-(3,4-dibenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-tribenzyloxyphenyl)-3-one is used as a benzyl derivative of chromen-4-one hydroxy-4H-chromen-4-one, as a catalyst - palladium on carbon (10 95 palladium), the concentration of the catalyst in the reaction mixture is 1 95 by mass; the reduction reaction is carried out in the solvent ethanol-acetic acid (5:11) at room temperature until the formation of the final product - 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one or /2-(3, 4,7-trihydroxyphenyl)-3-hydroxy-4H-chromen-4-one.

The choice of reaction components, solvents for the reaction - ethanol, DMF, acetic acid, catalysts - potassium hydroxide and palladium on carbon allows syntheses to be carried out at all three stages with the maximum possible yield and purity of intermediate and final products, eliminates unnecessary additional purification of final products and leads to to reduce reaction time.

Depending on the number and location of the substituents - hydroxyl groups in the chromenone bicycle, the claimed method allows one to widely modify the chemical structure of the final products and obtain a large set of 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromene-4 derivatives - they are natural compounds and their synthetic analogues.

Carrying out all the claimed reactions using the appropriate catalyst (potassium hydroxide, palladium on carbon) ensures high speed and selectivity of their course, which leads to the maximum yield and increased purity of the products in comparison with the first and second known analogues, and also excludes the use of flammable , flammable and poisonous solvents and allows, if necessary, to quickly develop an industrial method of synthesis of such compounds.

The use of palladium on carbon is due to high yields of reaction products and the convenience of regeneration of this catalyst (unlike, for example, palladium hydroxide).

Experimental variation of the temperature regime of the reaction showed that the specified temperatures are optimal for all three stages of synthesis, which allows obtaining compounds as pure as possible and with high yields. All compounds were obtained according to the claimed method, identified using H NMR spectra and the results of elemental analysis.

Table 1 provides comparative characteristics of the claimed method and methods of obtaining known analogues.

Table 1 000000 | or i) j

The solvent is about g. reactions / about stages

Ethanol, DMF,

The claimed method is acetic acid, 30.5 54 Z

MTBE

The analog method

IRgedeghidchne A. A. map

Asketg, shdo5 A. Nadetap,

Siido V. M. M. Nayepep, Methanol, tetrahydro- 38 32 Z

Mt.). R. map deg MiYidn, furan

Aay! Vavi, apa Umigo M.R.

V. Mepde, y. Honey. Spet., 43, 3752-3760 (2000

IVutions TvypeKamzha, Kepdo

Napaua, Zp!invi

Nidazpivbauavzni, TaKevnpi zidai, Viozsiepse, Ethanol, dichlor- 28 Not indicated With

VioyespppoIodu, apa methane

Viospetivhigu, 82, 8, Z

A!ydivy 2018, 1316-1322 2018

ISpiaga Wotzhagi, Vosagi

And isiapi, Sesiiia Rosi, u). | Methanol, ethanol, Bo 35 Z

May Spent 59, 16, 7598-| acetic acid 7616 (2016

Table 2 shows the characteristics (melting point, yields and NMR spectra) of the main reaction products obtained by the claimed method.

Nuclear magnetic resonance spectra were measured on a MAKIAM Megsig MA-400 spectrometer (400 MHz for "H NMR) in DMSO-Av solutions.

Elemental analysis was performed on the Eygomesiog-1200 device.

Table 2

Elementary and o

Compound T.pl., "C | Output, 90 analysis, in, NMR spectrum "H, 5 (m.ch) found (calculated) on OVp

Sh F Y S, 79.92; Н, 5.51 5.16 (4Н, а, СН»). 7.11 (1Н, 5, ! i: ov) 198-159 88 ((С7980:Н, 5.54)) ОН), 7.28-7.52 (17Н, Аг) (9) о он ovo 5.20 (2Н, 5, СН), 5.22 (2H, 5, you Ts FI S 7958: H 550 CH), 5.24 (2H, 5, CH), 6.57 2 s OV 145 94 (P. 79 69: n. 5.57) (H, 4, CH), 6.64 (H. 4, SN),

Ii n 7.27-1.17 (16Н, т, Аг), 13.56 (IN, 5, ОН)

ОВp (c) F , 5.14 (2Н, 5, СН»), 5.18 (2Н, 5,

From ov 192-493... 72 s Sho y. 192) CH"), 7.11 (1H, 9), 7.25-7.44

OH now (IBN, t), 7.48-7.53 (2H, t) (9)

OVp

PH 5.20 (2H, 5, CH), 5.22 (2H, 5, 4 vy o ov | 473 67 6b, 77.13; H, 5.13 | CH), 5.24 (2H, 5, CH). 7.11- (C, 77.68; H, 5.07) I8.03 (21H, t, Ag), 9.40 (1H, 5, on On) (9) on

F 9.54 (in, 1H), 9.26 (z, 2H), 8.08 o , (a, 9-7.8 Nl, 1H), 7.80-7.65 | he 281 85 s vot; B, 373 (t, ZN), 7.59 (4, 9-21 Ng,

OH pi 1H), 7.43 (1, 2-7.3 Nl, 1H), 6.89 (a, 9-8.5 H2, 1H) (9) on

F 5.45 (2H, 1, CH). 5.65 (IN, i, no o , SN). 5.90 (2H, a, CH), 7.71

More | eyes Ba | stva94 No 352) M, 9, CH), 8.20 (IN, 5, OH), he tt 9.95 (1H, p, OH). 10.10 (IN,

TSI re, ON). 11.0 (1H, bz, OH)

Below are examples of specific implementations.

Example 1. Preparation of 3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxy-phenyl)prop-2-en-1-one.

OVp on OVp

EUN, maon on F OVp , ato c) 24p, 50 9С

1.56 g (0.01 mol) of 2-hydroxyacetophenone and 3.18 g (0.01 mol) of 3,4-dibenzyloxybenzaldehyde were dissolved at 55 "С in 50 ml of ethanol. Then the temperature was brought to 50 "C and added 9 ml of 25% sodium hydroxide solution. The mixture was stirred for 6 hours at 50 "C. Then the mixture was cooled to room temperature and acidified to pH 2-3.

The precipitate was filtered and washed with a large amount of water and recrystallized from ethanol.

The product is gray crystals. Yield: 3.84 g (88 95 from theory).

IN MMe (400 МН, ОМ5О-ав) 6: 5.16 (4Н, и, СН»), 7.11 (1Н, 5, ОН), 7.28-7.52 (17Н, Ag)

Example 2. Preparation of 2-(3,4-dibenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one. he

OVp on F EYUN, BUT about F

These ------- | (c) 4.36 g (0.01 mol) of 2-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one was dissolved in 200 ml of ethanol, added 80 ml. 50 96 of an aqueous solution of potassium hydroxide, after 10 minutes of stirring, 80 ml was added. 30 9% hydrogen peroxide solution. The mixture was slowly heated to 60 "С (caution - gas evolution!), and after that it was stirred at room temperature for another 30 minutes and it was acidified to pH - 2-3. The precipitate that fell was filtered, thoroughly washed with water and recrystallized from ethanol.

The product is gray crystals. Yield: 3.24 g (72 95 from theory).

IN MMe (400 МН, ОМ5О-4в) 6: 5.14 (2Н, 5, СН»), 5.18 (2Н, 5, СНег), 7.11 (IN, а), 7.25-7.44 (IBN, t), 7.48-7.53 (2H, t)

Example 3. Preparation of 2-(3'4"-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-one.

OV ON about F EN, SNUSOON about F

Zh--783-2522.- on on on o (c) 3.24 g (0.0072 mol) of 3'4"-dibenzoxyphenyl-3-hydroxy-4H-chromen-4-one was dissolved in 400 ml of ethanol and 50 ml of glacial acetic acid, a catalyst - 10 95 Ra/C (1 95 mass) was added and the reaction mixture was stirred at room temperature in a hydrogen atmosphere for 24 hours.

The reaction mixture was filtered on silica gel from the catalyst. Solvents were removed under vacuum. The dry residue was washed with methyl tert-butyl ether (MTBE). The product was recrystallized from a water-ethanol mixture (1:1).

Yield: 1.65 g (85,905 from theory), Tpl - 250 "С (with osmosis) "Н MMe (400 МН, ОМ50-ав) 50: 9.54 (5, 1Н), 9.26 (5, 2Н), 8.08 (y, 9-7.8 H7, 1H), 7.80-7.65 (t,

ЗН), 7.59 (y, U9-2.1 Hl, 1H), 7.43 (y, 9-7.3 H2, 1H), 6.89 (a, 9-8.5 NI, 1H).

As can be seen from the text of the submitted materials, the proposed technical solution has the following advantages: - the duration of the synthesis is 30.5 hours (according to other known analogues - 28-52 hours); - allows you to increase the output and quality of final products to 54 95 (compared to the prototype method 32 95, with the second known analog 35 ob); - allows obtaining a wide range of analogs of natural compounds and varying the substituents of different electronic nature in the molecule.

З The claimed method of obtaining compounds of structure I is technologically simple, allows obtaining sufficiently pure target compounds and can be easily reproduced both in the laboratory and in production conditions.

Claims (1)

USEFUL MODEL FORMULA The method of obtaining substituted 2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-chromen-4-ones of general formula I OB, in (in) F on (in) where K - H, OH, OSNoSen5, B" - H, OSNeoSevH5, in which the condensation reaction of substituted acetophenone and substituted aldehyde is carried out in an organic solvent at a given temperature in the presence of a catalyst, after that the reaction of oxidative heterocyclization of an unsaturated ketone in an organic solvent in the presence of a catalyst and an oxidant is realized, after that - the reaction of removing the protective group (debenzylation) of the obtained benzyl derivative chromene -4-one 2 to the corresponding derivative 7,3,4y-flavon-3-ol in an organic solvent in the presence of a catalyst, which is characterized by the fact that the condensation reaction is carried out within b hours, as substituted acetophenone, 2-hydroxyacetophenone or 2-hydroxy-4-benzyloxyacetophenone is used, as aldehyde - 3 ,4-dibenzyloxybenzaldehyde in equimolar quantities, as a catalyst - sodium hydroxide, the condensation reaction is carried out in the solvent ethanol at 50 "C until the formation of 3-(3,4- dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one or 3-(3,4-dibenzyloxyphenyl)-1-(2,4- dihydroxyphenyl)prop-2-en-1-one; the oxidative heterocyclization reaction is carried out during 40 minutes, as an unsaturated ketone use /3-(3,4-dibenzyloxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one or 3-(3,4-dibenzyloxyphenyl)-1-(2, 4-dihydroxyphenyl)prop-2-en- 1-one, ethanol is used as a solvent, an aqueous solution (50 95) of sodium hydroxide is used as a catalyst, an aqueous solution of hydrogen peroxide 2595 is used as an oxidizer, until the formation of 2-(3,4- dibenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-tribenzyloxyphenyl)-3-hydroxy- 4H-chromen-4-one; the reaction of removing the protective group (debenzylation) is carried out in the solvent ethanol-acetic acid (5:1) at room temperature, as a benzyl derivative, 2- (3,4-dibenzyloxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-tribenzyloxyphenyl)-3- hydroxy-4H-chromen-4-one, as a catalyst - palladium on carbon (10 95 palladium), the concentration of the catalyst in the reaction mixture is 190 by mass; to the formation of the final product - 2-(3,4- hydroxyphenyl)-3-hydroxy-4H-chromen-4-one or 2-(3,4,7-trihydroxyphenyl)-3-hydroxy-4H-chromen-4-one.