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Publication numberUS3448190 A
Publication typeGrant
Publication dateJun 3, 1969
Filing dateMar 30, 1966
Priority dateMar 30, 1965
Also published asDE1492403A1
Publication numberUS 3448190 A, US 3448190A, US-A-3448190, US3448190 A, US3448190A
InventorsKarl Heinrich Baron, Rainer Klink, Fritz Reiff
Original AssigneeE A G Merck
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Uv absorbent compositions containing benzoyl-benzofurans
US 3448190 A
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Description  (OCR text may contain errors)

United States Patent US. Cl. 42459 8 Claims ABSTRACT OF THE DISCLOSURE For protection against UV-radiation, particularly against radiation being in the range responsible for sunburn, compositions comprising compounds of the following formula as well as salts thereof:

wherein R represents H, CH or C H R and R each represents H, alkyl of l-l2 carbon atoms, or together an alkylene chain of 3-4 carbon atoms,

R, and R each represents H, alkyl of l-12 carbon atoms, or together an alkylene chain of 3-4 carbon atoms,

R to R are the same or different and each represents H, SO H, alkyl of 1-12 carbon atoms; and the salts thereof, said salts being selected from the group consisting of sodium, potassium, mono-, di-, and triethanolammonium salts. Particularly efiective compounds are 2-benzoyl- 3 methyl-benzofuran, and 2 (2,4-dimethyl-benzoyl)- benzofuran.

This invention relates generally to a group of chemical compounds which are particularly useful as UV absorbents, and more particularly, to the use of these compounds in cosmetics to substantially eliminate the harmful effects of UV radiation.

Oxerexposure of the skin to ultraviolet rays within the ultraviolet range of about 290320 m produces radiation burns or erythema. When the sun is the radiation source, the resulting burning of the skin is known as sunburn. To afford maximum protection against erythema or sunburn, an agent which is a strong absorber of UV radiation is desirably applied to the exposed skin.

It is, therefore, a principal object of this invention to provide novel and unobvious chemical compounds.

Another object is to provide processes for the production of these novel and unobvious compounds.

A still further object is to provide cosmetic compositions which are resistant to UV radiation.

Still another object is to provide a process of administering the cosmetic compositions of this invention to mammals to prevent sunburn.

Upon further study of the specification and claims, other objects and advantages of the present invention will become apparent.

These objects are attained on the basis of the following compounds of Formula I:

lie R5 R7 TR: R4

wherein:

R1 is H, CH3, or C H R to R are the same or different and each represent H, alkyl having 1 to 12, preferably 1 to 4 carbon atoms, more preferably methyl, or the radical combinations selected from the group consisting of R and R and R and R form a single alkylene chain having 3 to 4 carbon atoms, and

R to R are the same or different and each represent H, SO H, or alkyl having 1 to 12, preferably 1 to 4 carbon atoms, and the salts thereof, preferably their sodium, potassium, mono-, dior triethanolammonium salts.

It was unexpectedly discovered that the compounds of Formula I and the salts thereof absorb, with low transmittance, UV radiation in the range of about 290-320 mp which is primarily responsible for the symptoms of burning of human skin.

The excellent UV absorption of the compounds of this invention are shown in the following table wherein the percent transmission of the compounds (A) Z-benzoyl- 3-methyl-benzofuran, and (B) 2-(2,4-dimethylbenzoyl)- benzofuran are tabulated as a function of wavelength 7\. The transmission is based on a 2% concentration of these compounds in a methanol solution, measured at a layer thickness of 0.005 mm.

Percent transmissivity It can be seen in the above table that UV radiation harmful to the skin and in the range between 290 and 320 m is effectively absorbed, while radiation above 330 mu which promotes tanning penetrates the protective coating. The other compounds of Formula I exhibit similar transmissivity values.

The compounds of this invention are particularly suitable for cosmetic applications wherein it is desired to reduce the transmittance of UV radiation in the range of 290-320 mg.

The compounds of this invention are particularly suitable for use in cosmetics which are designed to protect the skin from the sun, e.g. to avoid formation of freckles. Moreover, by using a weak concentration on skin exposed to the sun, tanning of the skin is promoted without sacrifice of the protection afforded against sunburn and erythema. In cosmetic compositions there are generally employed about 0.5 to 10%, preferably 1 to 5% of active UV absorbent by weight of the total composition.

Many of the commercially available UV absorbents such as ethoxyethly p-methoxycinnamate and methyl or (A) compounds wherein R is hydrogen, R to R have the previously indicated meaning, R to R represent H, or only one group is SO H.

and

(B) compounds wherein R1, R3 and R5 are H,

R and R are the same or different and each represent H, or CH and R to R represent H, or only one of these groups is SO3H.

(C) compounds wherein R is CH phenyl, or H when at least one of the groups R to R is alkyl of 1-12 carbon atoms, groups R to R is alkyl of 1-12 carbon atoms,

R to R have the previously indicated meaning, and R to R represent H, SO H, or alkyl of 1-12 carbon atoms, preferably methyl.

(D) compounds wherein R is CH R is H, or CH R and R are H, R, is H, or alkyl of l-l2 carbon atoms, R R and R are H, or one of them SO H, and R is H, or alkyl of l-12 carbon atoms.

(E) compounds wherein R to R have the previously indicated meaning, and

R to R represent H, alkyl of l-12 carbon atoms, preferably methyl, with the provision that one of R to R is SO H.

(F) compounds wherein R to R have the previously indicated meaning, and

R to R represent H, or alkyl of l-12 carbon atoms, and the salts of the compounds of (A) to (E), preferably their sodium, potassium, mono-, di-, or triethanolammonium salts.

In addition to methyl, the following are preferred alkyl substituents of the benzene ring of the benzofuran system, or at the phenyl ring: ethyl, propyl, isopropyl, nbutyl, isobutyl, sec.-butyl, tert.-butyl, n-amyl, isoamyl, nhexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-dodecyl. Desirably, there can also be a tetrahydronaphthyl-(5)- or -(6)- or an indanyl-(4)- or -(5)-radical on the carbonyl group instead of on the phenyl ring.

The compounds of Formula I which are particularly suitable are:

2-benzoyl-benzofuran. 2-(2,4-dimethylbenzoyl)-benzofuran, boiling point 190 C./1 mm. 2- 4-methylbenzoly) -b enzofur an. 2-(4-isopropylbenzoyl)-benzofuran, M.P. 105-107" C. 2-(tetrahydronaphthoyl-2)-benzofuran, M.P. 5860 C. 2-(4-tert.butylbenzoyl)-benzofuran, M.P. 122-124 C. 2-(3,4-dimethylbenzoyl)-benzofuran, M.P. 10l-l03 C. 2-(2,3,5-trimethylbenzoyl)-benzofuran, boiling point 260265 C./12 mm. 2-(2-isopropyl-5-methylbenzoyl)-benzofuran, boiling point 280-290 C./20 mm. 2-benzoyl-3-methyl-benzofuran, M.P. 51-52" C. 2-(2,4-dimethylbenzoyl)-3-methyl-benzofuran, boiling point 225228 C./ 12 mm.

4 2-(4-methylbenzoyl)-3-methyl-benzofuran, boiling point 224-226 C./l2 mm.

2- (4-dodecylbenzoyl)-3-methyl-benzofuran, boiling point 3053l0 C./l2 mm. 2-benzoyl-3,S-dimethyhbenzofuran, M.P. 81-83 C. 2-benzoyl-3-methyl-S-nonyl-bcnzofuran, boiling point 265-275 C./l2 mm. 2-benzoyl-3-phenyl-benzofuran. 2-benzoyl-S-methyl-benzofuran, as well as the sulfonic acid derivatives thereof, especially 2-benzoyl-benzofuran sulfonic acid, and 2-benzoyl-3-methyl-benzofuran sulfonic acid (the sulfonic acid group being presumably located at position 5 of the benzofuran system) and their salts, preferably the sodium salts.

The compounds of this invention are provided for all types of applications and in all types of cosmetic compositions in which UV absorbents are conventionally employed.

Thus, for example, it is possible to incorporate the compounds of this invention in lotions, emulsions, salves, creams, aerosols, and the like, which are usually employed for topical administration to humans. Such cosmetic compositions for topical administration can be described as having a form ranging from a liquid to thixotropic non- Newtonian liquids, to semi-solids such as pastes, to oily solids having, for example, a consistency like butter.

The compounds of this invention lacking sulfonic acid groups are soluble in mineral oils, vegetable oils, and fats, e.g. in liquid paraffin or saturated fatty acid triglycerides. The compounds of Formula I which do contain a sulfonic acid group, particularly 2-benzoyl-3-methyl-benzofuran sulfonic acid and its salts, preferably its sodium, potassium, monoethanolammonium-, diethanolammonium and triethanolammonium salts, are easily soluble in water.

The choice of carrier for these compounds depends therefore, on whether a sulfonic acid group is present. Generally, however, carriers usually associated with UV- resistant cosmetic preparations can be employed, such as solid or liquid parafiin, ceresin, mineral wax; vegetable or animals oils and fats such as olive oil, peanut oil, sesame oil or almond oil; cocoa butter, beeswax, mineral wax or carnauba wax, wool fat, spermaceti; fatty acids and fatty acid esters such as stearic, palmitic and oleic acids, glycerin monoor distearates, glycerin monooleate, isopropy myristate, isopropyl stearate, butylstearate; ethyl, isopropyl, cetyl, stearyl and palmityl alcohols; wetting agents of multivalent alcohols such as glycol, glycerin, sorbitol; emulsions of oil in water or water in oil systems, utilizing emulsifying agents (ionic, nonionic, cationic anionic, or ampholytic); thickeners such as methyl, ethyl or carboxymethyl cellulose, polyacrylic acid, tragacanth, agar-agar, gelatine. Further additives such as perfumes, preservative, or physiologically compatible dyestuffs can also be incorporated.

The UV absorbents of this invention can, if desired, be used in combination with one or more of the conventional UV absorbents, such as 2-phenylbenzimidaz0l-5- sulfonic acid-sodium salt, 3,4-dimethylphenylglyoxylic acid sodium salt, 4-phenylbenzophenone, isooctyl-4- phenylbenzophenone-2'-carboxylate.

The compounds of Formula I lacking a sulfonic acid group are obtained by the conventional reaction, in the presence of aluminum chloride, of the respective benzofuran-Z-carboxylic acid chloride (such as benzofuran-Z- carboxylic acid chloride, 3-methyl-, 3,5-dimethyl-, 3- methyl-5-nonyl-, 3-phenylor 5-methyl-benzofuran-2- carboxylic acid chloride), or the corresponding bromides with benzene or alkylbenzenes such as toluene, 0-, i or p-xylene, cumene, p-cymene, tert.-butylbenzene, indane or Tetraline.

Alternatively, these compounds can be obtained by the reaction of the sodium salts of salicylic aldehydes or ohydroxyphenylketones (such as salicylaldehyde, S-methylsalicylaldehyde, o-hydroxyacetophenone, Z-hydroxy-S- EXAMPLE 1 Suntan oil:

2-benzoyl-3-methylbenzofuran 2 Liquid parafiin 48 Butyl stearate 50 EXAMPLE 2 Suntan oil:

2-(2,4-dimethylbenzoyl)-benzofuran 2 Liquid paraifin 50 Isopropyl myristate 48 EXAMPLE 3 Aqueous solution:

2-benzoyl-b enzofuran sulphonic acid- 7 sodium salt 3 Sorbitol 3 Glycerin 3 Ethanol 20 Water 71 EXAMPLE 4 Suntan emulsion:

2-(2,4-dimethyl-benzoyl-3-methyl-benzofuran 3.0

Liquid parafiin 10.0 Polyol-monostearate-ethoxylate 10.0 Isopropyl myristate 10.0 Sorbitol solution 70% 5.0 Sodium laurylether sulfate 0.5 Water 61.5

EXAMPLE 5 Suntan lotion:

2-benzoyl-3-methyl-benzofuran-sulfonic acid 5 Triethanolamine Isopropanol 20 Sorbitol solution 70% 3 Glycerin 3 Water 59 EXAMPLE 6 Suntan cream:

2-(4-methylbenzoyl)-3-methyl-benzofuran 3 W001 fat 67 Olive oil 10 Water 20 EXAMPLE 7 Aerosol:

Mixture according to Example 1 or 2 '80 Mixture trichlorofiuoromethane and dichlorodi fluoromethane (70:30) (propellant gas) 20 EXAMPLE 8 Suntan cream:

2-benzoyl-3,S-dimethyl-benzofuran 2 2-phenyl-benzimidazol-S-sulfonic acid-trienthanoamine salt 50% 3 Cream base (oil/water or water/oil system) 95 6 EXAMPLE 9 Lipstick:

2 g. 2-benzoy1-3-methyl-S-nonyl-benzofuran are dissolved in g. of a molten lipstick mass. The resultant mass is then poured into lipstick moulds, cooled, and the moulded bodies removed upon solidification.

The lipsticks thus produced provide effective protection against ultra-violet rays within the range of 290 to 340 :m The use of this type of preparation is particularly advisable at high altitudes where the suns rays are intense.

The following examples are preferred embodiments illustrating the preparation of the compounds of Formula I.

EXAMPLE 12 (a) 38.9 g. 3-methyl-benzofuran-2-carboxylic acid chloride are dissolved in 50 ml. benzene and mixed with 28 g. aluminum chloride. The resultant mixture is refluxed for 1 hour and then decomposed with ice water. The benzene phase is separated, the aqueous phase extracted with benzene, and the solvent distilled oil from the combined benzene solutions. After the residue is distilled at 2l4-216 C./12 mm. there is obtained 43.8 g. 2-benzoy-l- 3-methyl-benzofuran, M.P. 51-52 C.

The following compounds can be prepared in the same manner:

With toluene: 2-(4-methylbenzoyl)-3-methyl-benzofuran With m-xylene: 2-(2,4-dimethylbenzoyl)-3-methyl-benzofuran With dodecylbenzene:

benzofuran (b) 12.2 salicylaldehyde and 18.2 g. w-chloro-2,4-dimethylacetophenone are dissolved in 250 m1. ethanol and mixed with 14 g. potassium carbonate. The mixture is refluxed for 4 hours, concentrated, and poured into water. Extraction with chloroform and subsequent distillation yields 2-(2,4-dimethylbenzoyl)-benzofuran having a boiling point of C./1 mm.

(c) 10 g. 2-benzoyl-3-methyl-benzofuran are dissolved in 100 ml. sulfonic acid. The mixture is then heated on a steam bath for an hour, cooled, and poured into saturated sodium chloride solution. The precipitated sodium salt of the 2-benzoyl-3-methyl-benzofuran sulfonic acid is filtered and recrystallized from water; no M.P. until 300 C.

The preceding examples can be repeated with similar success by substituting the generically and specifically described reactants and operating conditions of this invention for those used in the preceding examples.

What is claimed is:

1. A cosmetic composition for protection against UV- radiation, said composition comprising an intimate mixture of a cosmetically acceptable carrier and based on the weight of the total composition, about 0.5-10% by weight of a compound selected from the group consisting of a member of the formula v 4T Rs \0/-CO wherein R represents H, CH or G l-I R and R each represents H, alkyl of 1-12 carbon atoms, or together an alkylene chain of 3-4 carbon atoms,

R, and R each represents H, Alkyl of 1-12 carbon atoms, or together an alkylene chain of 3-4 carbon atoms,

R and R are the same or different and each represents 2- 4-dode cylbenzoyl) -3 -methyl- 7 H, SO H, or alkyl of 1-12 carbon atoms; and the salts thereof, said salts being selected from the group consisting of sodium, potassium, mono-, di-, and triethanolammoniu-m salts.

2. A composition as defined by claim 1 wherein said compound is selected from the group consisting of 2- benzoyl-benzofuran; 2-benzoyl-3-methyl-benzofuran; 2- (2,4 dimethylbenzoyl) benzofuran; 2 (2,4-di-methy1 benzoyl)-3-methy1-benzofuran and mixtures thereof.

3. A composition as defined by claim '1 wherein R is CH phenyl, or H when at least one of the groups R, to R is alkyl of 1-12 carbon atoms,

R to R have the previously indicated meaning, and

R to R represent H or alkyl of 1-12 carbon atoms.

4. A composition as defined by claim 1 wherein R1 is CH3,

R is H, or CH R3 and R5 are H,

R; is H, or alkyl of 1-12 carbon atoms,

R R and R represent H or SO H, and

R is H, or alkyl or 1-12 carbon atoms.

5. A composition as defined by claim 1 wherein R to R have the previously indicated meaning, and

R to R represent H, alkyl of 1-12 carbon atoms, with the provision that one of R to R is SO H.

6. A composition as defined by claim 1 wherein said compound is selected from the group consisting of 2- benzoyl 3 methyl-benzofuran, 2-(2,4-dimethylbenzoyl)- benzofuran, 2 (2,4 dimethylbenzoyl)-3-methyl-benzofuran, 2-benzoyl-3,S-dimethylbenzofuran, 2-benzoyl-3- methyl 5 nonyl-benzofuran, and 2-benzoyl-3-phenylbenzofuran.

7.' A process for decreasing the effect of UV radiation on mammalian skin, which process comprises topically adminstering a composition as defined by claim 1.

8. A process for decreasing the effect of UV radiation on mammalian skin, which process comprises topically administering a composition as defined by claim 2.

References Cited UNITED STATES PATENTS 3,012,042 12/1961 Hoi et al. 260346.2 3,165,537 1/1965 Jurd 260346.2

ALBERT T. MEYERS, Primary Examiner.

D. R. MAHANAND, Assistant Examiner.

US. Cl. X.R.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 443 190 Dated June 3 1969 Inventor s Karl Heinrich Baron, Rainer Klink and Fritz Reiff It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 6, line 72: Change "Alkyl" to --alkyl-.

Column 7, line 20 should read -R R and R represent H or SO H, and--.

SFGNED A D SEALED (SEAL) Atteflti EIWMMWJ" mun. mm. .m. Attcstm' 0mm Gomiasionar of Patents USCOMM-OC 60876-P69 ORM PO-1050 (10-69)

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3012042 *Dec 19, 1957Dec 5, 1961Belge Produits Chimiques SaBenzofurans
US3165537 *Jul 8, 1963Jan 12, 1965Jurd LeonardPreparation of benzofuran derivatives
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3892844 *Jul 20, 1972Jul 1, 1975Hoffmann La RocheMethod of protecting the skin from ultraviolet radiation
US4606913 *Dec 14, 1979Aug 19, 1986Lever Brothers CompanyHigh internal phase emulsions
US4994263 *Apr 30, 1990Feb 19, 1991L'orealSkin disorders
US5152983 *Nov 9, 1990Oct 6, 1992Chesebrough-Pond's Usa Co., Division Of Conopco, Inc.Mixture of 1,3-propanedione, 1-(4-methoxy-5-benzofurnyl)-3-phenyl and a carrier for topical application to human skin or hair
US5596106 *Jun 7, 1995Jan 21, 1997Eli Lilly And CompanyCannabinoid receptor antagonists
US5747524 *Sep 30, 1996May 5, 1998Eli Lilly And CompanyCannabinoid receptor antagonists
US7091240 *Apr 29, 2003Aug 15, 2006Oxigene, Inc.Destroying tumor cell vasculation; antitumor agents; anticancer agents
Classifications
U.S. Classification424/59, 549/468, 514/469, 424/64, 424/47, 514/939, 424/60, 514/972
International ClassificationA61K8/49, C07D307/80, A61Q17/04
Cooperative ClassificationA61K8/4973, A61Q17/04, C07D307/80, Y10S514/939, Y10S514/972
European ClassificationC07D307/80, A61K8/49H, A61Q17/04