DE2009600C - N 1 naphthyl K phenylene carboxy alkyl ureas and their uses - Google Patents

Description

The invention relates to N-l-naphthyl-N'-phenylenecarboxyalkyl ureas, which can be used as light stabilizers.

It is known that the short-wave UV radiation in the range from about 2800 to 32 (X) Å with a maximum at 2970 Å damages the human skin by erythema formation, the longer-wave radiation on the other hand tans without burning. In addition to this absorption maximum, a good light protection substance should at 2970 Å and a rapidly decreasing absorption in the direction of the longer-wave range, good skin tolerance have, be light and temperature resistant as well as in the most diverse cosmetic Let the preparations work in.

A number of well-known light protection substances show these properties, but have the major disadvantage that the substances do not adhere sufficiently to the skin. Sweat and water make you too quick washed off again, which means that the sunscreen should be applied several times a day got to.

Light stabilizers based on p, p'-di (carboxyphenyl) ureas have already been described. However, these have the disadvantage that their absorption maximum is 2850 A, i.e. too short-wave is. to give a good protective effect on the skin.

It has now been found that the N-1-naphthyl-N'-phenylene-carboxyalkyl ureas the general

NHCONH - Ph - COOR

in the Ph the o-, m- or p-linked. Phenylene ring and R is 2-ethylhexyl-, 2-butyloctyl-. 2-hexyldecyl-. 2-octyldodecyl-. ' 2-Decyltetradecyk 2-Dodecylcetyk

ίο 2-isohexyl-isooctyl-, 2-isoheptyl-isoundecyl-. Isooctyl, Means isononyl or butoxyethyleneyl group. Lichtrchutzmi'.tel represent that in the optimal Absorb area (see table 4 and the illustration) and are very well tolerated.

Another very important advantage is the special one Skin affinity of these substances. Washing attempts, as described below, show the excellent adhesion of the substances according to the invention to the skin and prove at the same time their superiority over various common light protection agents.

The experiments were carried out on fresh, carefully depilated pig skin, which is as close as possible to human skin in terms of its structure. accomplished. ^{The substances in each case in quantities of 3-10 "4} mol, dissolved in 2 ml of ethanol or paraffin oil (3 ^C Engler at 50 ° C), were applied to a 5 × 15 cm large and 0.3 cm thick skin. These are Amounts that are normally also used when using a light protection agent The skin surface was then washed with 100 liters of water (at 13 ° C.) / hour and, after methanol extraction, the amount of the respective substance remaining on the skin was determined by extinction measurements against corresponding blind tests.

As can be seen from Tables 1 to 3, the measurements showed that even after more than five hours, uninterrupted washing time, sufficient amounts of naphthyl urea are required for light protection according to the invention were on the skin while those used as comparative substances known and customary light protection agent p-methoxy cinnamic acid-2-ethylhexyl ester. Dipropylene glycol salicylic acid base, ρ - aminobenzoic acid unc p-aminobenzoic acid-2-ethylhexyl ester already after were washed off for a short time except for insignificant residues.

table

Washing time
1001 water (1.1 C) per hour

0 hours

1 hour

2 hours

3 hours

4 hours

5 hours

6 hours

Affinity half-life

(Hours)

Substance I.

2970 Λ
100%

86%
74%
64%
56%
51%
47%

3070 Λ

100%
84%
73%
62%
55%
49%
46%

Decrease in absorbance
Substance I!

2070 Ä
100%

3070 λ

100%

25%

14%

9%

6%

5%

4%

0.4

substance
2970 Ä

100%

41%

20%

12%

9%

6%

5%

0.7

III

3070 A

100%
45%
28%
20%
15%
13%
12%

0.8

Substance I = N-1-naphthyl-N'-p-phcnylcnairboO-nctyldodeeyl-oxy-urnsloff.

Substance II = p-methyl-oxycinnamic acid-2-ethylhexyl ester.

Substance III - Dipropylcnglykolsalicylsiuirecslcr (with the addition of a little isopropyl myristate). each dissolved in paraffin oil.

The "half-life of the affinity" should be defined as the time that is necessary. in order to rinse off half of the applied light-blocking substance from fresh pig skin (size 0.3 5 χ 15 cm) with water (! UO l / hour. } 3 ° C). Defined in this way, substance I is superior to substance II by 1430% and substance III by 670% in terms of its skin affinity.

2970 Λ Table 2 Decrease in German
in / IV
3071IA r Absorbance
Substance V
2970Λ 3070 Λ Washing time
IU) I water (13 C) per hour 100% Subs! 100% 100% 100% 0 hours. 93% 91% 10% 21% 0.5 hours 88% 84% 1% 0% 1 hour 81% 77% 0% 0% 2 hours 76% 73% 0% 0% 3 hours 74% 70% 0% 0% 4 hours 71% 67% o ⁰ :, 0% 5 hours 68% 65% 0% 0% 6 hours 50% 50% 0% 0% About 10 hours 10.0 10.0 0.125 0.175 Affinity half-life
(Hours)

Substance IV = NI-naphthyl-N'-p-phenylene-carbo ^ -äthylhe.xyl-oxy-urea.
Substance V = p-aminobenzoic acid, each dissolved in ethanol.

In the ethanol form of application, substance IV is about 6670% of substance V in terms of its skin affinity think.

Table 3

Washing time
100 1 water (13 C) per hour 2970 A Substa Decrease
na VI
3070 A ede r absorbance
2970 Ä Substance VII
. '' 1 " ¹ O Λ 0 hours 100% 100% 100% ] Lesson 94% 92% 14% 2Stui Jen 86% 85% 8th% 3 hours 78% 78% 4% 4 hours 71% 71% ">% 5 hours 63% 63% 1% 6 hours 56% 56% 0% About 7 hours 50% 50% 0% Affinity half-life
(Hours) 7.0 7.0 0.15 100% 13% 6% 3% 1% 0% 0% 0% 0.17

Substance VI = N-l-naphthyl-N'-m-phenylene-carbo-2- (iecyltetradecyl-oxy-urea. Substance VII = 2-ethylhexyl p-aminobenzoate. each dissolved in paraffin oil.

In paraffin-oily application form, the substance VI is the substance VII by 4380% with regard to their Superior to skin affinity.

Another advantage of the urea derivatives according to the invention, especially those with, / - branched Alcohol residue is. that they are with mineral oils in concentrations of 0.2 to 20 percent by weight, preferably 0.4 to 5.0 percent by weight, gel homogeneously. Jc according to the amount of naphthyl-ilarneas added gels with anti-sun protection can be used in all desired levels of flexibility between the Create values "very soft" and "very firm".

Other solvents can also be used in these gels as well as perfumes. I-Vrbslofle and the like are incorporated, such as B. Isopropyl myristate. Vegetable oils, the rump gland fat the corresponding water acid ester. Wool wax r.üfoholc. Polyethylene glycols various Molecular weight, polypropylene glycols

and other alcohols such as ethanol. Isopropanol. 2-ethylhexanol and others, especially in relation to the Guerbet reaction (J. Amer. Formerly Soc. 76.52 to 56 [1954]) available alcohols.

The compounds according to the invention are toxicologically harmless, as the following tests show to have:

LD ₅₁ on mice:> 10000 (mg / kg body weight, perorally).

Toxicity threshold in mice:> 10,000 (mg / kg Body weight, perorally), perorally no sure signs of intoxication;

Draize test on rabbits (compatibility on (> 5 animal mucous membrane)

unresponsive to conjunctivae. Cornea and iris, no pathological changes.

Patch test on rabbits (dermal tolerance).

there were no changes in the intact and scarciliary mouth and in the growth of the ileae.

no general (systemic) unreliable wedge reactions.

The production of the urine sulfate derivatives according to the invention takes place according to methods known per se.

Initially, the esters are expediently prepared the o-, m- or p-aminobenzoic acid. by treating the acids with a three-fold excess of the corresponding Alcohols mixed with an inert organic solvent such as uenzene, toluene or xylene, diluted and, if necessary, esterified with the addition of one of the usual esterification catalysts, until the calculated amount of water has deposited and the acid number of the batch <I is. The isolated lister is then placed in dry solvents such as benzene. Toluene or xylene, with the corresponding amount of naphthyl isocyanate with or without a catalyst (/. B. tin chloride, triethylenediamine, Dibutyltin dilaurate) and, after purification and isolation, receives the N-l-naphthyl-N'-o (or m- or p-1-phenylene-carboxy-alkyl-ureac in yields of about 70%.

The production method of the compounds is explained below by way of example.

Dimerization from straight to in // position

branched alcohols

(so-called Guerbet reaction.

.1. Amer. former Soc. 76. 52 to 56 [1954])

2-Hexyldecanol- (l): In a 500 ml four-necked flask with a stirrer. Thermometer. SlickstoffeinleiUmgsrohr and water separator with reflux condenser were added to 1 mol of n-Oclanol in a stream of nitrogen with stirring 0.175 mol of potassium in small portions. After the alcoholate had formed, I g of finely divided nickel were added to the reaction mixture, the stirring speed was increased and the mixture was heated to the boil until the calculated amount of water (9 ml) had separated out. The temperature rose to 240 ° C. within 4 hours. (In general, temperatures of 120 to 290 ° C. are required for this reaction step, although it is advisable to carry out the reaction in the autoclave under a pressure of about 100 to 150 atmospheres for the lower alcohols After cooling to below 100 ° C., 150 ml of water were added to the reaction mixture, the catalyst was filtered off, the phases were separated in a separating funnel, the alcohol layer was washed with 10% strength aqueous sodium hydroxide solution and the combined aqueous phases were extracted with diethyl ether of the non-aqueous phases. Drying over Na ₂ SO _4. Stripping off the ether and subsequent distillation in an oil pump vacuum gave a colorless oil of 1 Kp.

The others, in, / - position were analogous branched alcohols produced.

Ethylene glycol monohutyl ether was made by Adili tion of Äc | uimolar amounts of ethylene oxide on n-Bulb made according to a known procedure.

Aminobenzoic acid ester

ίο o-aminobenzoic acid 2-hexyldecyl (I) ester: Ii a four-necked flask with a capacity of 21 with a stirrer. Contact terminals and relays. Nitrogen pipe tube as well as water separator with return cooler winder 242.5g (I mol) 2-hexyldecanol- (l). 6S. 5 g (0.5 mol o-aminobenzoic acid and 1.5 g esterification contact in 140 ml xylene for 25 hours under nitrogen to boiling heated. The reaction temperature rose slowly to 190 "C; 9 ml of water were separated out, and the Säiirezalil sank below I. After suction over Kieselguhr and distillation in an oil pump vacuum.

whereby the excess alcohol was recovered, a light yellow oil of b.p. ">:

202 C (yield: 76 "", theory).

The other solvents of the o-amino-

2 «benzoic acid and that of m- or p-aminobenzoic acid manufactured.

N-l-naphthyl-N'-o (or m-, or p -) - phenylenecarboxy-alkvl-ureas

N-I- Naphlhyl- N'-o-phenylene -earbo-2-hexyldecyl-oxy-urea: 79.4 g (0.22 mol) ο-amiiiobenzoic acid-2-hexyldecyl- (l ) -cster were dissolved in 500 ml of dry benzene, with 33.5 g (0.2 mol) of naphthyl isocyanal and 0.5 g of dibutyl tin dilaural were added and the mixture was refluxed for 10 hours until no isocyanate more was to be proven. According to Linengen. Boiling about 1 hour in ethanol with the addition from activated charcoal and filtering off the substance crystallized in the form of light yellow, waxy crystals from K 65 'C (yield: 87% of theory).

The other naphthyl ureas according to the invention were carried out analogously. as listed in Table 4 are made.

The figure shows the absorption spectrum of one of the o-, m- and p-compounds and also the standardized A. sorpiionsvcrlauf designated with FBK * an ideal light protection agent, such as that from the International Lighting Commission was set up.

1 is the absorption curve of N-I-Naphlhyl-N'-p-phcnyIen-carbo-2-octyldodccyl-oxy-urea. 2 of N-1 -Naphthyl-N'-m-phenylene-carbo ^ -octyldodecyl-oxy-urea and 3 of the N-1-naphthyl-N'-o-phenylene-carbo-2-octyIdodecyl-oxy-urea.

UV-A, UV-B and UV-C is the well-known division of the spectrum, with UV-B representing the erythcm-forming part. The spectra were measured on 5 · 10 ⁵ m methanol solutions.

Table 4

connection

N-I-naphthyl-N'-p-phenylene-carbo-2-ethylhexyl-oxy-urethane

C 74.62
H 7.23
N 6.70

connection

N-l-Naphlhyl-N'-p-plienylen-carbo-2-butyloctyl-oxy-urnslofi "

N-1-naphthyl-N'-p-plienylene-carbo-2-hexyldccyl-oxy-urea

N-1-Naphlhyl-N'-p-phenylene-carbo-2-octyl-dodecyl-oxy-urine-stolT

N-1-Naphthyl-N'-p-phenylcn-carbo-2-dccyltetradecyl-oxy-urea

N-I -Naphthyl-N'-p-phenylene-carbo-2-dodecylcclyl-oxy-urostolT

N-1-naphthyl-N'-p-phenylene-carboxybutoxyethy leny! urea

N-1-Naphthyl-N'-p-phenylene-carboxyisononyl-urine sulfate

N- ί - Nd phi hy i - N -p-piicii y icii-Cüfbü-2-isohexyl-isodecyI-oxy-urea

N-l-Naphthyl-N'-p-phenylene-carbo-2-isoheplyl-isoundecyl-oxy-harn'Ho (T.

N-1-naphthyl-N'-m-phenylene-carbo-2-ethylhexyl-oxy-urea

N-1-naphthyl-N'-m-phenylene-carbo-2-butyloctyl-oxy-urea

N-l-Naphthyl-N'-m-phenylene-carbo-2-hexyldecyl-oxy-urinary stole

N-1-Naphthyl-N'-m-phenylene-carbo-2-octyldodecyl-oxy-urea T.

N-1 -Naphthyl-N'-m-phenylene-carbo-2-decyltetradecyl-oxy-urea

N-1-naphthyl-N'-m-phenylene-carbo-2-dodecylcetyl-oxy-urea

N-1 -naphthyl-N'-m-phenylene-carboxyisononyl-urea

N-1 -Naphthyl-N'-m-phenylene-carbo-2-isohexyl-isodecyl-oxy-urea

N-1 -Naphthyl-N'-m-phenylene-carbo-2-isoheptyl-isoundecyl-oxy-urea

N-1 -Naphthyl-N'-o-phenylene-carbo-2-ethylhexyi-oxy-urea

2 009 6OC here. I) se (! Cf. k Enamel ⁷ 8 27 700 C 75.91 75.94 Point Il 8.07 7.70 continuation N 5.90 5.92 111 C (Ai 26 200 Αικ C 76.94 77.0!) H 8.74 8.58 1950 N 5.28 5.47 91 C " 25 400 C 77.77 78.06 M 9.28 9.31 2960 N 4.77 4.66 85 C 28 400 C 78.47 78.34 H 9.72 9.74 2955 N 4.36 4.43 67 C 26 400 C 79.05 79.04 H 10.08 10.01 2950 N 4.01 3.91 80 C " 24 100 C 70.9! 71.14 H 6.45 6.61 2950 N 6.94 7.03 149 C 27 900 C 74.95 75.12 H 7.45 7.35 2960 N 6.48 6.37 121 C 27 700 C 76.94 77.21 H 8.74 8.63 2960 N 5.28 5.38 113 Χ 27 800 C 77.37 77.39 H 8.81 8.63 2950 N 5.01 5.02 Ι 14 C 12 100 C 74.63 74.64 H 7.23 7.20 2950 N 6.70 6.78 118 C 11 500 C 75.91 76.34 H 8.07 7.96 2970 N 5.90 6:00 am 107 C 11 500 C 76.95 76.81 H 8.74 8.62 2980 N 5.90 5.36 86'C 11 300 C 77.75 77.66 H 9.27 9.38 3000 N 4.77 4.84 79'C 11 200 C 78.47 77.65 H 9.72 9.57 30 (X) N 4.36 4.73 74'C I! 400 C 79.05 79.18 H 10.08 10.10 2990 N 4.01 3.90 72 C 11 600 C 74.95 74.61 H 7.45 7.35 3000 N 6.48 6.44 127'C 10 900 C 76.94 76.81 H 8.74 8.83 2980 N 5.28 5.31 91C 11 100 C 77.37 77.65 H 8.81 8.95 2980 N 5.01 4.86 1I4'C 11 400 C 74.62 74.88 H 7.23 7:00 2980 N 6.70 6.63 109'C 2960- 3160 (Plateau)

2 ') 7OA

200

2 (K)

400

900

KK)

100

900

700

800

100

L 5 (K)

500

300

200

400

600

900

100

21

22nd

21

10

10

10

10

10

10

C 1!

connection

N-1-Naphthyl-N'-o-phenylcn-carbo-2-butyloelyl-oxy-urea

N-I-naphthyl-N'-o-phenylene-carbo-2-hexyldecyl-oxy-urea

N-1-Naphthyl-N'-o-phenylene-carbo-2-octyldodecyl-oxy-urinary-urine

N-1-naphthyl-N'-o-phenylene-carbo-2-jecyltetradecyl-oxy-urea

N-1 -Naphthyl-N'-o-phenylene-carbo-2-dodecylcetyl-oxy-urea

N-1 -naphthyl-N'-o-phenylene-carboxyisooctyl urea

N-1-naphthyl-N'-o-phenylene-carboxyisononyl-urea

N-1-Naphthyl-N'-o-phenylene-carbo-2-isohexyl-isodecyl-oxy-urine sulfate

N-1-Naphthyl-N'-o-phenylene-carbo-2-isoheptyl-isoundecyl-oxy-urea

The substances according to the invention can be used individually or in a mixture in all for light protection agents Incorporate the usual cosmetic preparations.

You can z. B. produce greasy and non-greasy creams by adding suitable ointment bases or by mixing with solvents such as ethanol, optionally with the addition of emulsifier

2 009 6OC here gcr. ) t 10 10 600 = 2970A }. C 75.92 76.06 10 600 = 3070 Λ Il 8.07 7.90 '■ »HIM 10 600 continuation N 5.90 6.02 Enamel (Λ) 9 900 analysis C 76.94 77.06 Point 9 900 H 8.74 8.56 2950 9 9 (K) N 5.28 5.29 68 C 3120 9 500 C 77.77 77.75 (Plateau) 9 500 H 9.28 9.32 2930 9 500 N 4.77 4.62 65 C 3150 9 600 C 78.47 78.60 (Plateau) 9 600 H 9.72 9.69 2930 9 6 (X) N 4.36 4.43 71 "C 3100 Il 400 C 79.05 78.15 (Plateau) 11 400 H 10.08 10.10 2920 10 400 N 4.01 3.90 66 "C 3110 9 800 C 74.61 74.71 (Plateau) 9 800 H 7.23 7.14 3000 9 800 N 6.69 6.63 55 "C 9 400 C 74 95 74.84 9 400 H 7.45 7.40 2950- 9 400 N 6.48 6.52 120 "C 3165 12 100 C 76.94 76.79 (Plateau) 12 100 Fl 8.74 8.02 2950 12 100 N 5.28 5.12 117 C 3140 12000 C 77.37 77.54 (Plateau) 12000 H 8.81 8.95 2890- 12,000 N 5.01 5.04 97 "C 3070 (Plateau) 295σ- 120'C 3070 (Plateau)

ren, liquid sunscreen preparations, which can also be found in Let the Acrosolform bring, prepare. The gel-forming properties of the compounds can also be exploit in a corresponding manner. In general, concentrations of 3.5 to 5.5% are based on the total weight, the active ingredients door a good light protection sufficient.

1 sheet of drawings

Claims (2)

Patent claims: 1. N-I -Naphthyl-N'-phenylene-carboxyalkyl ureas of the general formula NHCONH - Ph - COOR in the Ph the o-, m- or p-linked plienylene ring and R is 2-ethylhexyl-, 2-butyloctyl-. 2-hexyldecyl-, 2-octyloodecyl-, 2-decyltetradecyl-. 2-dodecylcetyl-, 2-isohexyl-isooctyl-. 2-isoheptyl-isoundecyl-, Isooctyl, isononyl or Butoxyäthylenyl-Grup-ie means. 2. Use dei ureas according to claim 1 as a light stabilizer. formula