CS202170B1 - 2-phenyl-3-furyl-2-propenic acid,derivatives thereof and process for preparing them - Google Patents

Abstract

New 3-furyl-2-phenyl-2- propenoic acid derivs. have formula (I) in which M is a lower mono-, di- or trialkanolammonium ion, the cation of a 2-5C alpha-amino acid, an ammonium cation, the cation of an alkali metal, lower alkyl or H. (I) have high absorption in the range 290-320 nm and are useful as sunscreening agents. They are soluble in water and water-alcohol mixts, and they are stable towards atmospheric oxygen. (I) have no irritant effect on the skin. In an example 3-furyl-2-phenyl-2-propenoic acid (i.e. (I; M=H)) is prepd. in 85% yield by reacting 136g phenylacetic acid with 128 g furfural in 200ml acetic anhydride in the presence of 280 ml triethylamine for 6 hrs. at room temp.

Description

The present invention relates to 2-phenyl-3-furyil-2-poopenoic acid and derivatives thereof, and to a process for the preparation of this acid and derivatives thereof. The compounds are useful as light-protective agents.

As protective equipment before. Light radiation to protect human skin from sunburn (erythema) is mainly used in oil and alcohol-soluble organic. compounds, esters, amides and nitriles of cinnamic acid and substituted cinnamic acid, further substituted acrylic acid, p-aminobenzoic acid, etc.,. as well as Schiff bases and the like can be used. All of these compounds exhibit ultraviolet absorption and a range from 280 to 320 nm (biological portion of the spectrum) while having a high extinction coefficient.

SUMMARY OF THE INVENTION It is an object of the present invention to provide water-soluble organic compounds whose spectral characteristics are such that they can be used as light radiation filters.

The present invention provides 2-phenyl-3-furyl-2-propenoic acid and its derivatives of formula (I):

wherein M is C 2 -C 5 mono-, di- or tri- alkanolamine, ammonium or alkali metal, C 1 -C 5 alkyl, or hydrogen.

0 0 0 0 0

The essence of the method. The preparation of 2-phenyl-3-furyl-2-propenoic acid and its derivatives according to the invention is characterized in that:. reacting furfural with phenylacetic acid in the presence of acetic anhydride and triethylamine to form an acid of formula I wherein M is hydrogen and this acid is optionally converted to the corresponding derivative by treatment with a basic compound or a C 1 -C 5 alkanol, in the presence of a solvent allowing dissolution as follows. ready. compounds.

In a preferred embodiment of the process of the present invention, the basic compound is mono-. di-. . or triethanrlamine, glycine or sodium hydroxide.

It is also preferred that water, an alcohol or an aqueous-alcoholic mixture are used as solvents in the above process.

The above reaction for the preparation of 2-phenyl-3- [1- (1-methyl) -propyl] -cyclohexan-2-yl-2-phenyl-3-ol is carried out. in the presence of an alkaline catalyst at room temperature.

The acid thus obtained is reported after release. by reacting with a lower C 1 -C 5 alkanol in the presence of sulfuric acid or a sulphate exchange agent, while heating to give 2-phenyl-3-furyl-2-propenoic acid methyl ester.

Synthesis of a derivative of said acid is accomplished by mixing 2- (071-3) -2- (1-2-2) -acetic acid with an organic basic compound (e.g., alkamines, amino acids), or an inorganic basic compound in the presence of a solvent such as. for example water or an alcohol to obtain a homogeneous solution. Heat treatment releases the resulting acid salts

2-Phenyl-3-fu-21-2-ene first.

The products obtained according to the invention absorb intensively the radiation in the ultraviolet part of the spectrum in the range from 290 to 320 nm with a high extinction coefficient. So prepared. the compounds are well soluble in water, in aqueous alkaline. Furthermore, these compounds are stable with respect to the action of atmospheric oxygen and do not show. there is no adverse effect on the skin and, last but not least, there is no change in the properties of these compounds when used in the skin. in the form of solutions or emulsions in the form of creams and lotions as a component of the liquid aqueous phase.

With regard to the effect of the compounds according to the invention, the following may be mentioned:

a) i to. the Department of Skin Diseases of the Faculty of Medicine in Plovdiv was treated. 98 patients using the compounds of the invention, and no positive skin reaction was found after the test.

(b) By analogy, 28 patients were treated at the Institute of Dermatology at the Medical Academy in Sofia; and there was no positive reaction in this allergy test, i.e. all tests were negative. No skin changes (such as erythrem, edema, etc.) were observed. The compounds according to the invention have been used as protective agents against the effects of light radiation, the compounds in the form of cosmetic creams containing 2-phenyl-3-furylacrylic acid derivatives. at a concentration of 1%.

The compounds of the above. invention. the process of its preparation will be illustrated by the following examples.

He did

To a solution of 136 g of phenylacetic acid in 200 ml of acetic anhydride and 280 ml of triethylamine was added. adds. 128 ml furfural. The mixture thus prepared was added to the mixture. The mixture is left at room temperature for 6 hours and then 500 ml of concentrated hydrochloric acid and 1 liter of water are added. The product obtained is extracted with ether. The ether extract is washed with 200 ml of water and further extracted with 5 liters of 2% sodium hydroxide solution. The alkaline extract obtained is washed. twice with 200 ml of ether, using the same portion each time, then purged with air until the ether used is removed and finally acidified with a 20% hydrochloric acid solution to pH 1. The resulting precipitate is 2-phenyl-3-furyl- 2-poopene. The separated filtrate is extracted again with ether to completely extract the product, and then the ether extract is evaporated while drying. The total yield is 182 g (85% of theory). The acid obtained has the following formula:

Melting point 141 to 140 ° C. 143 ° C

Amax 304 nm,

E = 12000 1st moT ¹ . cm ' ¹ .

The product obtained is well soluble in ether and alcohol and poorly soluble in natural oils.

Example 2

1.83 g of monoethanolamine are dissolved in 25 ml of water, and 6.42 g of 2-phenyl-3-furyl-2-propenoic acid is then added. The mixture is then heated to boiling and 2 g of activated carbon are added. The mixture is allowed to boil for 15 minutes, then hot filtered and finally cooled. The precipitate was collected by filtration and dried. The product is recrystallized from water. Yield 6.5 g (80% of theory). The salt obtained has the formula

H0GH _from CH _ft NH ₃

Mp 185-189 ° C

Λ _max : 302 nm

E: 20600 cm ¹ . mol ¹

Elemental Analysis for C ₁₅ H ₁₇ O ₄ (275)

Calculated: C 65.4%, H 6.2%, N 5.1%;

Found: 65.5% C, 6.1 ° / o H, 5.8 ° / o N.

Example3

1.07 g of diethanolamine and 2.14 g of 2-phenyl-3-furyl-2-propenoic acid are mixed with 30 ml of water. This compound is completely dissolved. This solution is boiled for 15 minutes together with 2 g of activated carbon and then filtered while hot. The aqueous phase was evaporated in vacuo. The residue is in the form of an oily viscous mass which gradually solidifies. Yield 1.95 g (60% of theory). The salt obtained has the formula

(носн ₂ сн ₂ ) _а мн _а

Λ _max = 304 nm,

E = 18550 cm ¹ . mol ¹ ,

Elemental analysis for C ₁₇ H ₂₀ O ₅ (319) Calculated: C 63.9%, H 6.6%, N 4.4%; Found:% C, 62.4;% H, 6.70;

Example 4

1.49 g of triethanolamine are dissolved in 30 ml of water and 2.13 g of 2-phenyl-3-furyl-2-propenoic acid are added. The mixture is then boiled for 15 minutes together with 2 g of activated carbon, filtered while hot and the water is evaporated in vacuo. The residue obtained is an oily liquid which solidifies after complete vacuum drying. Yield: 3.12 g (corresponding to 90% of theory).

The salt obtained has the formula

HO (HOCHjCHJjNH

Λ max = 305 nm.

E = 19420 1. cm ^-1 . mol ' ¹

Elemental Analysis for C ^ jHOOs (362)

Calculated: C 63.0%, H 6.9%;

Found: C 61.2, H 6.96,

Example 5

The mixture consisting of 0.2 g of glycine and 0.5 g of 2-phenyl-3-furyl-2-propenoic acid is heated together with 20 ml of water until homogenization. After cooling, a precipitate forms, which is filtered and dried.

Yield 0.5 g;

Λ max 309 nm;

E = 31300 cm -1. mol-1;

Molecular Weight = 288.

Example 6

2-Phenyl-3-furyl-2-propenoic acid is neutralized with sodium hydroxide in aqueous medium. This procedure will:. yields the salt in quantitative yield.

Λ max ⁼ 303 nm;

E = 16000 cm -1. mol-1; ,

Molecular Weight = 236.

Example7

A solution of 214 g of 2-phenyl-3-furyl-2-propenoic acid in 2 liters of methanol containing 4 ml of concentrated sulfuric acid is heated at 65 ° C for 6 hours. The reaction mixture obtained is diluted with an equivalent. volume of water to form a precipitate of 2-phenyl-3-furyl-2-propenoic acid methyl ester.

Yield: 220 g (96% of theory). The ester obtained has the formula:

Mp 82-83 ° C;

Λ max = 308 nm;

E = 125000 1 mol ¹ . cm1

The ester obtained dissolves well in alcohol, ether, natural oils, and poorly dissolves in carbon tetrachloride and hydrocarbons. .

Claims (4)

1. 2-Phenyl-3-furyl-2-propenoacylic acid and derivatives thereof having the meaning of M in which the moiety is a C2 -C5 mono-, di- or tri-alkanolamine, an ammonium cation or an alkali metal cation, and an alkyl group containing 1 to 5 carbon atoms. 5 carbon atoms or hydrogen. 2. A process for the preparation of 2-phenyl-3-furyl-2-pentenoic acid or its derivatives according to claim 1, which comprises reacting furfural with phenylacetic acid in the presence of acetic anhydride and triethylamine to form a general acid. of formula I, wherein M is hydrogen, and this acid is optionally converted to the corresponding derivative by treatment with a basic compound or a C 1 -C 5 alkanol in the presence of a solvent to dissolve the compound so obtained. 3. Method. 2. The method of claim 2, wherein the basic compound is mono-, di- or triethanolamine, glycine or sodium hydroxide. 4. The process according to claim 2, wherein the solvent used is water, an alcohol or an aqueous alcoholic mixture.