Stabilization of household, body-care and food products by using benzotropolone containing plant extracts and/or related benzotropolone derivatives

Abstract

Disclosed is the use of benzotropolone derivatives of formula ##STR00001##
wherein
R.sub.1, R.sub.2 and R.sub.7 independently from each other are hydrogen; C.sub.1-C.sub.3alkyl; or COR.sub.8;
R.sub.3 is hydrogen; or COOR.sub.9
R.sub.4 is hydrogen; or C.sub.1-C.sub.3alkyl;
R.sub.5 is hydrogen; hydroxy; C.sub.1-C.sub.3-alkoxy; or O(CO)R.sub.10;
R.sub.6 is hydrogen; C.sub.1-C.sub.3alkyl; or COR.sub.8; or
R.sub.5 and R.sub.6 together may form a five or six membered ring; or
R.sub.6 and R.sub.7 together form a five or six membered ring; and
R.sub.8, R.sub.9, R.sub.10 independently of each other are C.sub.1-C.sub.30alkyl;
for protecting body-care and household products from photolytic and oxidative degradation.

Claims

1. A method for protecting body-care and household products from photolytic and oxidative degradation by incorporating benzotropolone derivatives of formula (1) therein ##STR00030## where R.sub.1, R.sub.2 and R.sub.7 independently from each other are hydrogen; C.sub.1-C.sub.3 alkyl; or COR.sub.8; R.sub.3 is COOR.sub.9; R.sub.4 is hydrogen; or C.sub.1-C.sub.3 alkyl; R.sub.5 is hydrogen; hydroxy; C.sub.1-C.sub.3-alkoxy; or O(CO)R.sub.10; R.sub.6 is hydrogen; C.sub.1-C.sub.30 alkyl; or COR.sub.8; or R.sub.5 and R.sub.6 together may form a five or six membered ring; or R.sub.6 and R.sub.7 together form a five or six membered ring; R.sub.8 and R.sub.10 independently of each other are C.sub.1-C.sub.30 alkyl; and R.sub.9 is C.sub.2-C.sub.30 alkyl.

2. The method according to claim 1, wherein R.sub.1 is hydrogen; COR.sub.8; or C.sub.1-C.sub.30 alkyl; R.sub.2, R.sub.4 and R.sub.5 are hydrogen; R.sub.3 is COOR.sub.9; R.sub.6 and R.sub.7 independently from each other are hydrogen; C.sub.1-C.sub.30 alkyl; or COR.sub.8; or R.sub.6 and R.sub.7 together form a five or six membered ring; and R.sub.8 is defined as in claim 1.

3. A method for protecting body-care and household products from photolytic and oxidative degradation by incorporating benzotropolone derivatives of formula (1) therein ##STR00031## wherein R.sub.1 is hydrogen; or COCH.sub.3; R.sub.2, R.sub.4 and R.sub.5 are hydrogen; R.sub.3 is COOC.sub.3H.sub.7; R.sub.6 and R.sub.7 independently from each other are hydrogen; or COCH.sub.3; or R.sub.6 and R.sub.7 together form a five or six membered ring.

4. The method according to claim 1, wherein the benzotropolone derivatives of formula (1) are selected from compounds of formulae ##STR00032## ##STR00033## ##STR00034## are used.

5. The method according to claim 1, wherein the body-care product is a product for the skin and its adnexa.

6. The method according to claim 5, wherein the body-care products are selected from skin-care products, bath and shower additives, preparations containing fragrances and odoriferous substances, hair-care products, dentifrices, deodorizing and antiperspirant preparations, decorative preparations, light protection formulations and preparations containing active ingredients.

7. The method according to claim 5, wherein the body-care products are selected from body oils, body lotions, body gels, treatment creams, skin protection ointments, shaving preparations and skin powders.

8. The method according to claim 5, wherein the body-care products contain fragrances and odoriferous substances which are selected from scents, perfumes, toilet waters and shaving lotions (aftershave preparations).

9. The method according to claim 5, wherein the body-care products are hair-care products and are selected from shampoos, hair conditioners, products for styling and treating hair, perming agents, hair sprays and lacquers, hair gels, hair fixatives and hair dyeing or bleaching agents.

10. The method according to claim 5, wherein the body-care products are decorative preparations and are selected from lipsticks, nail varnishes, eye shadows, mascaras, dry and moist make-up, rouge, powders, depilatory agents and suntan lotions.

11. The method according to claim 5, wherein the body-care products contain active ingredients and are selected from hormone preparations, vitamin preparations, vegetable extract preparations and antibacterial preparations.

12. The method according to claim 1 in which the household product is a household cleaning and treating agents.

13. The method according to claim 12 wherein the household cleaning and treating agents are selected from washing, rinsing and dishwashing agents, shoe polishes, polishing waxes, floor detergents and polishes, all purpose cleaners, bath and toilet cleaners, kitchen cleaners, car shampoos and waxes, neutral, acidic and alkaline cleaners, metal, glass and ceramic cleaners, textile care agents, agents for removing rust, color and stains (stain remover salt), bleaches, furniture and multipurpose polishes, surface protecting formulations, film forming formulations, air care formulations and candles.

14. A body-care product, which comprises at least one benzotropolone derivative of formula (1) according to claim 1.

15. A household cleaning and treating agent, which comprises at least one benzotropolone derivative of formula (1) according to claim 1.

Description

EFFICACY COMPARISON TO STATE-OF-THE ART STABILIZERS

Example 1

(1) The following colored basic shampoo formulation is prepared:

(2) TABLE-US-00007 Sodium Laureth Ether Sulfate 10% Cocamidopropylbetaine 3% Citric Acid to pH 5 FD&C Blue No. 1 0.002% Stabilizer 0.01%

(3) The following stabilized and unstabilized samples of this formulation are prepared for light stability testing:

(4) 1. unstabilized basic shampoo formulation

(5) 2. basic shampoo formulation plus 0.01% of the compound of formula (B-1)

(6) 3. basic shampoo formulation plus 0.01% of the compound of formula (B-2)

(7) 4. basic shampoo formulation plus 0.01% of the compound of formula (B-32)

(8) 5. basic shampoo formulation plus 0.01% of the compound of formula (B-18)

(9) The formulations were filled into 30 ml glass bottles and irradiated in an ATLAS Suntest XLS+Xenon Lamp (light intensity 500 W/m2, spectrum of light adjusted to indoor conditions, sample chamber temperature: 32 C.).

(10) Results after 15 Hours Irradiation.

(11) TABLE-US-00008 Sample Observation after irradiation 1 Faded/colorless 2 No change 3 No change 4 No change 5 No change

(12) Results after 30 Hours Irradiation.

(13) TABLE-US-00009 Sample Observation after irradiation 1 Colorless 2 No change 3 No change 4 No change 5 faded

(14) All stabilizers increased the stability of the formulation significantly. Stabilizer of formula (B-18), according to current invention, showed additionally the benefit that it did not alter the initial color, which is of advantage if specific desired shades don't allow for yellowish colored components.

Example 2

(15) The following colored basic shampoo formulation is prepared:

(16) TABLE-US-00010 Sodium Laureth Ether Sulfate 10% Cocamidopropylbetaine 3% Citric Acid to pH 5 Dye 0.002% Stabilizer 0.01%

(17) The formulation is colored with PURICOLOR Blue ABL9 (BASF, FD&C Blue No. 1, Acid Blue 9), and PURICOLOR Red ARE33 (BASF, D&C Red 33, Acid Red 33), respectively.

(18) The following stabilized and unstabilized samples of this formulation are prepared for light stability testing:

(19) 1. unstabilized basic shampoo formulation

(20) 2. basic shampoo formulation plus 0.01% of the compound of formula (B-18)

(21) 3. basic shampoo formulation plus 0.01% of TINOGARD TL (BASF)

(22) The formulations were filled into 30 ml glass bottles and irradiated in an ATLAS Suntest XLS+Xenon Lamp (light intensity 500 W/m2, spectrum of light adjusted to indoor conditions, sample chamber temperature: 32 C.).

(23) Results for Blue Colored Shampoo after 12 Hours Irradiation.

(24) TABLE-US-00011 Sample Observation after irradiation 1 Faded/colorless 2 No change 3 No change

(25) Results for Blue Colored Shampoo after 25 Hours Irradiation.

(26) TABLE-US-00012 Sample Observation after irradiation 1 Faded/colorless 2 Very slightly lighter 3 Faded/colorless

(27) Results for Red Colored Shampoo after 10 Hours Irradiation.

(28) TABLE-US-00013 Sample Observation after irradiation 1 Faded/pale brown 2 No change 3 No change

(29) Results for Red Colored Shampoo after 25 Hours Irradiation.

(30) TABLE-US-00014 Sample Observation after irradiation 1 Faded/colorless 2 Very slightly lighter 3 Faded/colorless

(31) Compound of formula (B-18) performed significantly better than state-of-the-art broadbandUV absorbers like TINOGARD TL with both tested dyes.

Example 3

(32) The following stabilized and unstabilized samples were prepared for antioxidation testing:

(33) 1. pure castor oil

(34) 2. castor oil containing 0.1% of compound of formula (B-32)

(35) 3. castor oil containing 0.1% of the antioxidant TINOGARD TT (BASF)

(36) 4. castor oil containing 0.1% of the antioxidant BHT

(37) 5. castor oil containing 0.1% of Quercetin

(38) The samples were placed in a RACIMAT and heated to 140 C. An airflow of 15 L/min was adjusted. The airstream bubbles through each heated sample and afterwards through a water reservoir. Thus all volatile organic compounds formed by the oxidation process are carried into the water reservoir by the airstream. The conductivity of the water reservoir is monitored online during the measurement. Once oxidation starts volatile organic compounds like formic acid are transported into the water reservoir which results in a rapid (exponential) increase of conductivity. The time until oxidation starts is called induction time.

(39) The results are listed in the table below.

(40) TABLE-US-00015 Sample Induction Time 1 7.7 hours 2 10.5 hours 3 9.3 hours 4 9.2 hours 5 8.5 hours

(41) Sample 2, comprising a stabilizer according to the present invention, exhibits better oxidation stability compared to the state-of-the-art antioxidants like TINOGARD TT (Ciba) or BHT, and also performs significantly better than natural polyphenolic structures like Quercetin.

Example 4-15: Preparation of Body-Care and Household Formulations

(42) TABLE-US-00016 Example 4: Preparation of a sprayable hair styling gel Phase Ingredients (w/w) % A carbomer (1% dispersion) 0.30 water, demin. 30.00 B glycerol 2.00 methylparaben 0.20 C water, demin. ad 100 PVP/VA copolymer 8.00 triethanolamine (88%) 0.12 EDTA, disodium salt 0.01 D light stabilizer of formula (B-18) 0.01 fragrance 1.00
Preparation:

(43) The components (A) are dispersed at room temperature.

(44) (B) is mixed under heating until the paraben is completely dissolved and then (B) is added with gentle stirring to (A).

(45) (C) is blended until it is completely dissolved and is slowly added under stirring to the mixture of (A) and (B).

(46) (D) is blended until completely dissolved and is slowly added under stirring to the mixture of (A), (B) and (C).

(47) The transparency of the gel can be increased by adding small amounts of triethanolamine (pH=5.6-5.75).

(48) TABLE-US-00017 Example 5: Preparation of a baby shampoo Ingredients (w/w) % cocoamidopropylbetaine 35.00 water, demin. ad. 100 citric acid q.s. (pH) polyquaternium-15 0.15 perfume oil 0.30 chlorophyll 0.20 light stabilizer of formula (B-2) 0.02 Compound of formula (AO 01) 0.02 colorant (D&C Yellow No. 5) 0.02 sodium chloride 0.30
Preparation:

(49) Surfactant and water are blended until a homogeneous solution is obtained. The pH is adjusted to 6.0-6.5 with citric acid. The other components are added, stabilizers are premixed with the fragrance oil. The mixture is stirred until it is completely dissolved.

(50) TABLE-US-00018 Example 6: Preparation of a perfumed toilet water Ingredients (w/w) % ethanol, 96% 60 d-limonene 5 cedrene 1.5 citronellol 0.5 savin 0.5 stabilizer of formula (B-44) 0.05 light stabilizer of formala (AO 01) 0.05 light stabilizer of formula (AO 02) 0.03 Antioxidant of formula (AO 06) 0.02 S,S-EDDS 0.01 colorant (D&C Yellow No. 5) 0.1 water ad. 100
Preparation:

(51) The components are thoroughly mixed in the indicated sequence at 50 C. A clear homogeneous solution is obtained.

(52) TABLE-US-00019 Example 7: Preparation of a lipstick, non-greasy Ingredients (w/w) % Carnauba wax 2.5 Beeswax, white 20.0 Ozekerite 10.0 Lanoline, anhydrous 5.0 Cetyl alcohol 2.0 Liquid paraffin 3.0 Isopropyl Myristate 3.0 Propylene glycol recinoleate 4.0 CI Pigment Red 4 9.0 CI Pigment Blue 15 1.0 Stabilizer of formula (B-32) 0.05 Castor Oil ad 100

(53) TABLE-US-00020 Example 8: Preparation of a lipstick, transfer resistant Ingredients (w/w) % Cyclomethicone 41.50 Isodecane 10.00 D&C Red No. 7 8.00 Synthetic wax 6.00 Isostearyltrimethylpropane siloxysilicate 5.00 Cetylstearate/acetylated lanolin, 90:10 5.00 Ceresin 4.00 Paraffin 3.00 Titanium dioxide 2.00 Methylparaben 0.30 Propylparaben 0.10 Antioxidant of formula (AO 04) 0.10 stabilizer of formula (B-1) 0.10

(54) TABLE-US-00021 Example 9: Preparation of a Rouge (powder) Ingredients (w/w) % Talcum 56 Zinc Stearate 15 Rice starch 15 Iron Oxide Red 12 Perfume q.s. stabilizer of formula (BTE) 0.1

(55) TABLE-US-00022 Example 10: Preparation of a Foundation cream Ingredients (w/w) % Titanium dioxide 12.79 Oleyl alcohol 4.57 Glyceryl stearate 3.65 Propylene glycol 3.65 Stearic acid 1.83 Magnesium aluminium silicate 0.91 Triethanolamine 99% 0.91 Iron Oxide Yellow 0.64 Iron Oxide Red 0.32 CI Pigment Brown 6 0.37 Carboxymethyl cellulose 0.10 stabilizer of formula (B-44) 0.10 Water ad 100

(56) TABLE-US-00023 Example 11: Preparation of an Eyeliner Ingredients (w/w) % Polysaccharide resin (Kama KM 13, Kama) 8.00 Iron Oxide Black 6.50 Carnauba wax 1.00 Triethanolamin, 99% 1.00 Hydrogenated polyisobutane 1.00 Hydrogenated polydecene 1.00 Sorbitan sesquioleate 1.00 Polysaccharide resin (Kama KM 13, Kama) 8.00 Xanthum gum 0.50 Carboxymethyl cellulose 0.40 Magnesium aluminium silicate 0.40 Methyl paraben 0.35 Stearic acid 2.50 Lecithin 0.20 Imidazolidinyl urea 0.10 stabilizer of formula (B-32) 0.10 Antioxidant of formula (AO 05) 0.05 Water to 100

(57) TABLE-US-00024 Example 12: Preparation of an Eyelash Makeup Ingredients (w/w) % Paraffin Wax 10.00 Starch 5.00 Polyethylene 5.00 Iron Oxide Black 7.00 Carbomer (Carbopol, B F Goodrich) 0.50 Hydroxyethylcellulose 0.50 Panthenol 2.00 stabilizer of formula (B-2) 0.05 Water ad 100

(58) TABLE-US-00025 Example 13: Preparation of a Nail Varnish Ingredients (w/w) % Poly(1-trimethylsilylpropylene) 0.30 Nitrocellulose 12.00 Alkyd resin 10.00 Dibutyl phthalate 4.00 Camphor 2.00 Butyl acetate 49.50 Toluene 20.00 Pigment Red 57.1 1.00 Quaternary bentonite 1.00 stabilizer of formula (B-18) 0.20 Light stabilizer of formula (AO 04) 0.10
Preparation of Formulations of Household Products

(59) TABLE-US-00026 Example 14: Preparation of a green-colored glass detergent: Ingredients (w/w) % anionic/amphoteric surfactants (Lumorol RK) 0.7 butyl glycol 5.0 isopropanol 20.0 d-limonene 4.00 colorant (D&C Green No. 2) 0.05 light stabilizer of formula (AO 02) 0.05 light stabilizer of formula (B-1) 0.05 water, demin. ad. 100
Preparation:

(60) The components are dissolved in the indicated sequence until a clear homogeneous mixture is obtained.

(61) TABLE-US-00027 Example 15: Preparation of a floor wax Ingredients (w/w) % wax mixture 12 white spirit ad 100 d-limonene 4.00 light stabiliser of formula (B-18) 0.10
Preparation:

(62) The components are stirred in the indicated sequence until a homogeneous mixture is obtained.

Synthesis Example (1): Preparation of B-20

(63) 1,7-dibutyl-2,3,4,6-tetrahydroxy-5H-Benzocyclohepten-5-one (CAS-No. 16492-78-7) (1.4 g) is dissolved in 40 ml of toluene and 0.8 ml triethyl orthoacetate and heated to 120 C. until ethanol evaporation ceases. The mixture is then evaporated to dryness and the residue lyophilized from dioxane after filtration from silicagel in order to remove dark impurities. The resulting yellow powder is soluble in hexane.

(64) .sup.1H-NMR (CDCl.sub.3, 300 MHz): 9.00 (OH); 7.45 (d, 1H); 6.82 (d, 1H); 3.65 (dq, 1H); 3.53 (dq, 1H); 2.85 (t, 2H); 2.72 (t, 2H); 1.88 (s, 3H); 1.48-1.66 (m, 4H); 1.29-1.45 (m, 4H); 1.18 (t, 3H); 0.90 (dt, 6H).

(65) .sup.13C-NMR (CDCl.sub.3, 75 MHz): 13.88; 13.95; 14.74; 22.51; 22.75; 24.80; 26.29; 31.23; 31.94; 34.11; 58.45; 112.85; 119.40; 127.11; 129.45; 129.52; 132.62; 133.91; 144.66; 150.61; 152.75; 181.76.

Synthesis Example (2): Preparation of B-2

(66) 0.50 g of catechol (44.3 mmol, 98%) and 1.28 g of gallic acid octyl ester (44.3 mmol, 98%) are dissolved in 30 ml phthalate buffer (pH=5) and 10 mL ethyl acetate at room temperature. 3.0 mg (21.8 U/mg) of commercial (Sigma-Aldrich) laccase from T. versicolor are added and the mixture is stirred for 2 days at room temperature.

(67) The organic phase is then separated and concentrated in vacuo to yield 1.02 g of crude compound B-2. After recrystallization from ethanol/water the desired product B-2 is yielded in 1.26 g as an dark orange powder. Melting point: 79 C. (decomposition).

(68) .sup.1H-NMR (DMSO, 300 MHz): 14.77 (s, 1H, OH), 10.00 (s, 2H, 20H); 8.27 (s, 1H); 7.612 (m, 2H); 7.48 (d, 1H); 4.28 (t, 2H); 1.73 (m, 2H); 1.16-1-42 (m, 10H); 0.85 (t, 3H).

Synthesis Example (3): Preparation of B-1

(69) 6.74 g of catechol (60 mmol, 98%) and 8.66 g of gallic acid propyl ester (40 mmol, 98%) are dissolved in 400 mL phosphate buffer (pH=5) and 120 mL ethyl acetate at room temperature. 45.2 mg (21.8 U/mg) of commercial laccase from T. versicolor are added and the mixture is stirred for 4 days at room temperature.

(70) The organic phase is then seperated and concentrated in vacuo to yield 13.40 g of crude product. After recrystallization from water the desired product B-1 is yielded in 7.34 g as an orange powder. Melting point: 139 C.

(71) .sup.1H-NMR (DMSO, 300 MHz): 14.75 (s, 1H, OH), 10.15 (s, 1H, OH); 9.90 (s, 1H, OH); 8.26 (s, 1H); 7.61 (d, 1H); 7.60 (s, 1H); 7.48 (d, 1H); 4.25 (t, 2H); 1.76 (m, 2H), 0.99 (t, 3H).

Synthesis Example (4): Preparation of B-32

(72) To a solution of 3.00 g purpurogallin in 40 ml of pyridine 2.56 ml of acetic anhydride is added dropwise. After stirring for 1 h at 100 C. the mixture is evaporated to dryness and the orange residue is suspended in diethyl ether. The precipitate is filtrated off and dried in vacuum to yield 0.59 g of crude compound B-32. After boiling in diethyl ether/ethyl acetate (1:1) the desired product is obtained in 0.42 g as a yellow powder.

(73) .sup.1H-NMR (DMSO, 360 MHz): 15.29 (s, 1H); 11.38 (s, 1H); 7.57 (d, J=11.6, 1 H); 7.35 (d, J=8.95, 1 H); 6.99 (s, 1H); 6.78 (dd, 1H); 2.34 (s, 3H); 2.30 (s, 3H).

Synthesis Example (5): Preparation of B-23

(74) Purpurogallin (0.50 g) is dissolved in 20 ml of toluene and 0.43 ml triethyl orthoacetate and heated to 120 C. until ethanol evaporation ceases. The resulting orange suspension is then evaporated to dryness and the residue is stirred in dichloromethane. The precipitate is filtrated off and dried in the vacuum at 25 C. 450 mg of the desired product are isolated as an orange powder.

(75) .sup.1H-NMR (CDCl.sub.3, 360 MHz): 14.61 (s, 1H); 8.56 (s, 1H); 7.34 (d, J=11.5, 1 H); 7.19 (d, J=9.5, 1 H); 6.86-6.80 (m, 2H); 3.72-3.59 (m, 2H); 1.92 (s, 3H); 1.24 (t, J=7.1, 3 H).

Synthesis Example (6): Preparation of B-36

(76) Compound B-37 is suspended in 10.0 ml of HCl.sub.aq. 0.1 solutions and stirred for 18 h at 25 C. The orange-yellow precipitate is filtrated off and dried in the vacuum. 0,318 g of the desired product are isolated as a beige powder.

(77) .sup.1H-NMR (DMSO, 360 MHz): 15.26 (s, 1H); 7.56 (d, 1H); 7.33 (d, 1H); 6.98 (s, 1H); 6.65 (dd, 1H); 2.30 (s, 3H).

Synthesis Example (7): Preparation of B-37

(78) To a solution of 0,636 g B-23 in 6.0 ml pyridine 0,207 ml of acetic anhydride are added at room temperature. The brown-orange solution is stirred for 1.5 h at room temperature and added to 30.0 ml of ice-water and stirred for 15 min at 0 C. The orange suspension is filtrated off and dried in the vacuum. 0,620 g of the desired product are isolated as an orange powder.

(79) .sup.1H-NMR (DMSO, 360 MHz): 14.78 (s, 1H); 7.68 (d, 1H); 7.43 (d, 1H); 7.26 (s, 1H); 6.82 (dd, 1H); 3.59-3.56 (m, 2H); 2.31 (s, 3H); 1.89 (s, 3H); 1.16 (t, 3H).

Synthesis Example (8): Preparation of B-38

(80) Compound B-1 (1.50 g) is dissolved in 35 ml of toluene and 1.89 ml triethyl orthoacetate and heated to 120 C. until ethanol evaporation ceases. The resulting orange suspension is then evaporated to dryness and the residue is stirred in 10.0 ml diethylether. The precipitate is filtrated off and dried in the vacuum at 25 C. 1.20 g of the desired product are isolated as a yellow powder.

(81) .sup.1H-NMR (CDCl.sub.3, 360 MHz): 8.39 (s, 1H); 8.30 (s, 1H); 7.77 (s, 1H); 7.57 (d, 1H); 7.34 (d, 1H); 4.31 (t, 2H); 3.70-3.57 (m, 2H); 1.98 (s, 3H); 1.84-1.82 (m, 2H); 1.24 (t, 3H); 1.06 (t, 3H).

Synthesis Example (9): Preparation of B-39

(82) To a solution of 0.40 g B-23 in 4.0 ml pyridine 2,651 ml of acetic anhydride are added at room temperature. The brown mixture is stirred for 20 h at room temperature and added to 40.0 ml of ice-water and stirred for 15 min at 0 C. The beige suspension is filtrated off and the orange-yellow residue is dried in the vacuum. 0,198 g of the desired product are isolated as a yellow powder.

(83) .sup.1H-NMR (CDCl.sub.3, 360 MHz): 7.14 (d, 1H); 6.92 (s, 1H); 6.78 (d, 1H); 6.52-6.47 (m, 1H); 3.703.54 (m, 2H); 2.35 (s, 3H); 2.29 (s, 3H); 1.87 (s, 3H); 1.21 (t, 3H).

Synthesis Example (10): Preparation of B-5

(84) Compound B-1 (0.35 g) is dissolved in 4.0 ml of pyridine at room temperature. 0.50 ml of acetic anhydride are added dropwise and the solution is stirred for 16 h at room temperature. Then the mixture is added to 5.0 ml of ice-water and stirred for 30 min at 15 C. The yellow precipitate is filtrated off, washed with water and dried in the vacuum at 30 C. 0.337 g of the desired product are isolated as a yellow powder.

(85) .sup.1H-NMR (DMSO, 360 MHz): 8.45 (s, 1H); 8.16 (d, 1H); 7.88 (d, 1H); 7.50 (s, 1H); 4.31 (t, 2H); 2.38 (s, 3H); 2.33 (s, 3H); 2.30 (s, 3H); 1.83-1.77 (m, 2H); 1.03 (t, 3H).

Synthesis Example (11): Preparation of B-7

(86) To a mixture of 0.20 g B-41 in 4.0 ml HCl.sub.aq 0.1N solution 0.5 ml of THF are added at room temperature. The brown suspension is stirred for 6 h at 60 C. The mixture is then evaporated to dryness and the residue was suspended in water. The brown precipitate is filtrated off and dried in the vacuum at 25 C. 0.12 g of the desired product are isolated as a brown-red powder.

(87) .sup.1H-NMR (DMSO, 360 MHz): 14.36 (s, 1H); 10.75 (s, 1H); 8.35 (s, 1H); 7.70 (s, 1H); 7.63 (d, 1H); 7.37 (d, 1H); 4.15 (t, 2H); 2.21 (s, 3H); 1.67-1.61 (m, 2H); 0.87 (t, 3H).

Synthesis Example (12): Preparation of B-41

(88) Compound B-38 (490 mg) is dissolved in 2.0 ml of pyridine at room temperature. 0,154 ml of acetic anhydride are added dropwise and the brown solution is stirred for 1 h at 25 C. Then the mixture is added to 5.0 ml of ice-water and stirred for 30 min at 15 C. The yellow precipitate is filtrated off, washed with water and dried in the vacuum at 30 C. 0.33 g of the desired product are isolated as a yellow powder.

(89) .sup.1H-NMR (DMSO, 360 MHz): 8.40 (s, 1H); 7.85 (d, 1H); 7.60 (d, 1H); 7.54 (s, 1H); 4.25 (t, 2H); 3.53-3.50 (m, 3H); 2.30 (s, 3H); 1.88 (s, 3H); 1.81-1.71 (m, 2H); 1.15 (t, 3H); 0.98 (t, 3H).