TW201223934A - 3-(2,3-dimethylphenyl)-2-butenal and its use as perfume - Google Patents

Abstract

The invention discloses the aldehyde 3-(2, 3-dimethylphenyl)-2-butenal, a method for its preparation from 1-bromo 2, 3-dimethylbenzene, and its use in perfumes.

Description

201223934 6. DISCLOSURE OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention discloses an acid 3-(2,3-dimethyl benzoxanthene)-2-butenal prepared from 丨-bromo 2,3_-toluene. The method and its use in perfumes. [First cutting technology] Aromatic is widely used as a fragrance and fragrance in cosmetics, perfumes and many household items. It is known that alpha, beta-unsaturated aromatic acids, such as substituted cinnamon roads, have a unique aroma and are therefore suitable for use in the perfume industry. The purchase of 5237 Α reveals certain aromatic, acetophenone-based, U-, methods, their use as perfumes, and their use as intermediates in the preparation of 3-arylpropanal. It has a musky aroma. SUMMARY OF THE INVENTION The perfumery and household goods industry is continually demanding novel perfumes that have attractive, novel and unused aromas to increase the aroma of choice and to adapt the fragrance to changing fashion needs. In addition, each substance needs to be Q, and it is synthesized and has consistent quality. High Purity and Aroma Needed The present invention provides a novel α,β-unsaturated aromatic complex having a rich and embroidered fragrance, a strong flavor; and an improved method of making the same. In the following 'if not otherwise specified, halogen means F, Cl, Br or I, && Cl, Br or I; alkyl means straight chain, branched chain and cyclic alkyl group; as intended to mean n-butyl chain . The main pass of the present invention is a compound of the formula (I), 3 201223934

%/C

(I) wherein the isomer and the z-isomer:::: double bond has a (Z) or (8) configuration. The method described herein generally uses the E-isomer and the Z-isomer. mixture. Both types of hetero-anthracene λ Xing are suitable as fragrances. The other method of the present invention is the method (A) of the compound of the formula (I) (wherein the compound of the formula (I) is as defined above, and I), and all of its preferred embodiments (A), the method (A)句人斗', ττλ 3 (Π) compound and acid (a) in the presence of water (A);

Wherein R1 and R2 are the same or different and each other is independently Cw alkyl, or R1 and R2 are linked to each other and are combined to form a ((CH2)2- or -(CH2)3- group; 'Therefore, the two oxygens connected to R1 and R2 and the C atoms connecting the two oxygen atoms form a five- or six-membered ring; the acid (A) is selected from the group consisting of the following: · · · · · · · Monocarboxylic acid, C2 6 dioxane, perchlorinated C2_4 monocarboxylic acid, perfluorinated. . Rolling C2_4 early carboxylic acid, hydrochloric acid, p-A 4 201223934 Benzene acid, HES acid, exchange resin and mixtures thereof Sulfuric acid, an acidic ion commonly used in organic synthesis (A) usually provides a mixture of compounds. The (8) and (Z) stereoisomers of the two stereoisomers may be separated by isomers of organic chemistry. Preferably, R1 and R2 are the same or different and independently of each other. Methyl or better, R1 and r2 force π

2 is the same and is a methyl group or an ethyl group; R1 and R2 are even more preferably a methyl group. A mixture of such polymers The acidic ion exchange resin is preferably selected from the group consisting of styrene and a mixture of perfluorinated or linear polyethylene, and the S〇3H group is functionalized. Acidic ion exchange resin - This is a copolymer of styrene and dibutyl benzene containing more than 5% divinylbenzene (preferably a giant network... a group of fluorinated polyethylene). The S03H group is functionalized. The acid (A) is preferably selected from the group consisting of a stalk of a stalk, a sulphuric acid, a butyric acid, a tris-ethyl acetoacetic acid, a salt warmer, a slanting armor a group consisting of methanesulfonic acid, sulfuric acid, and an acidic ion exchange resin and a mixture thereof. The acid (A) is more preferably acetic acid. The reaction (A) is optionally carried out in the solvent (a), and the solvent (4) is selected from tetrahydrofuran (THF, 7n b } Group of acetonitrile, propionitrile, Cl-4 alcohol and mixtures thereof. Solvent (A) is preferably THF. Reaction (A) can be carried out in the presence of salt (A); salt (A) and its 5 201223934 An alkali metal salt derived from an acid as defined above for all preferred embodiments of the acid, independent of the acid (A) (A). Salt (A) formic acid, acetic acid p-toluenesulfonate. More preferably derived from a salt selected from The following 淼p < group of acid alkali metal salts: two acids, butyric acid, trichloroacetic acid, two & χ - rat B , hydrochloric acid, methanesulfonic acid, sulfuric acid and acid hydrazine; 丄 &...^ 丨 ion parent resin and its mixed salt (A) is preferably derived from sodium or unloaded metal salt sodium formate and methyl salt (A) or even more Preferably, it is selected from the group consisting of sodium acetate and potassium acetate. The salt (A) is especially sodium acetate. The salt (A) is preferably derived from the acid (a) used. In detail, the acid (A) is acetic acid and the salt (A) The reaction temperature of the reaction is preferably from generation to generation, more preferably from io〇c ' even more preferably from 85 to 95. The reaction (A) is preferably at atmospheric pressure to 1 Torr. Bar, preferably at atmospheric pressure to 5 bar, or even better at atmospheric pressure to 2 bar. The reaction process is controlled by standard techniques such as (4) resonance spectroscopy (NMR), infrared spectroscopy (IR), and high efficiency. Liquid chromatography (HpLc), liquid chromatography mass spectrometry (LCMS) or thin layer chromatography (TLC), and when the initial conversion of the shell exceeds 95% or when no starting material is detectable The reaction mixture can be started to be processed. The time required to occur will depend on the precise reaction temperature and the exact concentration of all reagents, and may not be due to batch The reaction time of the reaction (A) is preferably from 3 to 48 hours, more preferably from 1 to 24 hours, even more preferably from 3 to 12 hours. 201223934 Water Moire is preferably (π) The compound has a molar amount of 1 to 1 (10) times, more preferably 1 to 50 times, even more preferably 1 to 10 times. Preferably, 〇_〇1 to 100 molar equivalents, more preferably 〇1 to 5 molars are used. When I, even more preferably 1 to 10 moles of acid (Α)' molar equivalent is based on the molar number of the compound of formula (II). The amount of solvent (Α) is preferably 0.5 to the weight of the compound of formula (II) 2 times, more preferably 1 to 10 times, even more preferably 2 to 5 times.

The molar amount of the salt is preferably 0.01 to 1 times, more preferably 0.5 to 5 times, even more preferably 0.1 to 2 times the amount of the acid (Α). The combined amount of k (A) with water, and optionally solvent (a) and optionally salt (A), is 2 to 20 times, more preferably 3 to 1 times, the weight of the compound of formula (II). Even better is 5 to 7 times. The reaction (A) is preferably carried out under an inert atmosphere. After the reaction (A), the formula f, the children &, and the s species are separated by standard methods, such as evaporating volatile components, squeezing, washing, drying, concentrating, crystallizing, and/or Steaming.

Preferably, the volatile component of the reaction mixture is dehydrated by evaporation under reduced pressure. The aqueous solution by addition of a base (A-basified) is preferably sodium hydrogencarbonate. The non-volatile residue is preferably alkalized, and the alkali (A-basification) test (A-tested) is preferably added so that the pH of the resulting mixture is from 7 to 12, more preferably from 8 to 1. Oh, it's even better 8 to 9. Alternatively, the formula (I) can be isolated as follows: the reaction mixture can be diluted with water, followed by a solvent selected from the group consisting of a scorpion, a sputum or an ethyl ketone (preferably acetic acid C 1 -4). 201223934 Alkyl esters, more preferably ethyl acetate - • isopropyl acetate or butyl acetate, singly, followed by concentration and depending on the main oxime of the solvent, wish to distill the extract. After the reaction, in the separation period, 4, as appropriate, any aqueous solution of De 4 is used, and an aqueous solution of the base (A-wash) is preferably used or brine. The purine base (A-wash) is preferably sodium hydrogencarbonate. Preferably, any k rows can be extracted. "Mesh, the extraction preferably uses solvent (A-extraction) into the solvent (A-extraction) preferably or even better, firstly /:, ethyl acetate or isopropyl acetate. Dilute with water and "benzene extraction minus The reaction mixture is concentrated underneath, and then any right deuteration can be dried as appropriate. "It is preferably carried out by base distillation. The parent uses magnesium sulfate or sodium sulfate. The distillate is reduced, preferably in a reduced steaming. Finely crystallized or in the other 4 of the present invention, the formula (wherein the compound of the formula (1) is purified as defined above), the compound of the right (wherein the formula (Π), ^ and VIII all preferred embodiments. (Π) compound is 对 / / / / / / / 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且 且Any mixture of the subject matter of the present specification is a compound of the formula (τ), the compound of the formula (II) wherein the compound of the formula (I) is defined above, ^ Φ I ) and all its preferred embodiments. (B) comprising a reaction (8) carried out in a solvent, wherein the reaction (8) is carried out in three consecutive steps ") (B); And U) are in Los ⑴ step of formula (v)) is reacted with reagent (v)) of the reaction (leaf, 201,223,934

Wherein R 3 is a halogen; the reagent (Bal) is selected from the group consisting of _ hua u, Zhen Xuan, fun, sodium, magnesium, aluminum, rhenium or calcium;

Step (b) is a mixture of the compound of the formula (IV) and the reaction mixture produced by the step (a);

(IV) wherein R1 and R2 have the same definitions as above, and all preferred embodiments thereof; step (c) is a mixed reagent (Be) and a reaction mixture produced by the step (b), and the reagent (BC) is Water, C 1 · 4 yeast or a mixture thereof; the solvent (B) is selected from the group consisting of benzene, toluene, diphenylbenzene, hexane, cyclohexane, Cw alkyl hexanol, heptane, THF, di-Cb4 alkyl ether, a group consisting of sulfhydryl-THf, I, 2-dimethoxyethane, anthracene, 4-dicrosane, Cl_4 trialkylamine, and mixtures thereof; step (b) directly after the reaction (al) Or, after the reaction (al) 201223934 and before step (b), the reagent (B a2 ) is added to the reaction (a2 ) by the anti-deer (ai, the reaction mixture produced; the reagent (Ba2) is selected from a group of Zn, A, Ca, Zr and/or Ti, a C..4 alkoxide and a mixed halide Cm alkoxide and mixtures thereof. Compounds of formula (III) and formula (IV) are known The compound can be prepared according to known methods. The reaction (al) is carried out in the presence of the catalyst (B), and the catalyst B) is selected from the group consisting of UC1, T1CU, BiC13 and Pbcl2. Group. Month R3 is preferably bromine. The reagent (Bal) is preferably a sodium isopropyl H-group clock, a second butyl lithium or a third butyl lithium; the reagent (Bal) is more preferably sodium, zhen, shun, n-butyl clock or third butyl. Lithium base; the reagent (Bal) is even more preferably n-butyl lithium. When the reaction (a2) is carried out, the reagent (Bal) is preferably selected from the group consisting of _Calta, Li, C4 alkyl lithium, lithium, sodium and magnesium; more preferably halogenated Cl_4 magnesium, The n-butyl group, the second butyl group, the -butyl butyl lithium, lithium, sodium and magnesium, and even more preferably the n-butyl lithium, lithium, sodium and magnesium reagents (Be) are preferably water. The solvent (B) is preferably selected from the group consisting of benzene, dimethyl methylcyclohexane, hydrazine, THF, 2-methoxyethane, 1,4 dioxin, benzene, diphenyl, hexane, cyclohexane. 10 201223934 Group consisting of diethyl ether, dibutyl sulfonate, decyl _THF, triethylamine and mixtures thereof; solvent (Β) is more preferably THF. The formula (Ba2) is preferably selected from the group consisting of vaporized zinc, vaporized aluminum, aluminum triisopropoxide and titanium triisopropoxide. The reaction temperature of the reaction (B) is preferably 丨〇〇. It is preferably ～80°C to 40°C, and even more preferably ^(^ to 2〇t>c. The reaction (B) is preferably carried out under atmospheric pressure. Ο ❹ Reaction (B) The reaction time is preferably from 3 to 48 hours, more preferably from 1 to 24 hours, even more preferably from 2 to 12 hours. The amount of the solvent (B) is preferably the weight of the compound of the formula (ΙΠ) @ 2 to 4〇倍, more preferably 3 to 10 times, even more preferably 5 to 7 times. Use 0.9 to 1〇 molar equivalent, better 1〇 to 5〇 molar equivalent, even better 1.0 to 2.0 The molar equivalent of the compound of the formula (IV), the molar equivalent is based on the molar number of the compound of the formula (III). Preferably, 0.9 to 10 mole equivalents, more preferably 1.0 to 5.0 mole equivalents, even more preferably 1. G to 2. G molar equivalent reagent (Bal), molar equivalent based on the molar number of the compound of formula (). Preferably 1.0 to 50 molar equivalents, more preferably 1 to 3 molar equivalents, 10 mole equivalents of reagent (Bc) Moer's equivalent is based on the molar number of the formula (Π) compound. Even more ί using 0 9 to 10 molar equivalents better LO to 5.00 molar equivalents, U to 2. 〇 molar equivalent reagent (Ba2) , Moore equivalent based on UI1) The number of molar composition. 'B' is preferably carried out under an inert atmosphere. Suitable inert gas is argon 11 201223934 gas, other rare gases, low boiling alkanes (preferably Ci 3 alkane (methane 'ethane and propane)) and nitrogen. After that, the compound of the formula (π) is separated by a standard method, #evaporating the volatile component 'extracted, optionally washed and dried, concentrated and crystallized or distilled. ~ preferably extracting any aqueous phase, preferably extracting Use solvent (Β_提取) to enter the person's '丨王马肀笨* ^ % u曰Dry any organic phase from a cool 可视 ,, preferably using magnesium sulfate. Better concentrated by distillation Preferably, the distillation is carried out under reduced pressure. I is preferably prepared by crystallization or distillation under reduced pressure to purify the compound of formula (8). The formula prepared by method (B) has been prepared (11 method (B); In the case of /, continuous "solution" (preferably) is preferably the same as in the case of non-separating (π) compound 4. 1) and depending on the case, the solvent (Α) agent (5) and (two m) are preferably - The crane reaction is carried out, and the solvent (A) used in the same is the same. Use of a perfume or a compound of the formula (1) as a fragrance. The use of the compound of the invention _ φ compound. The compound of the formula (11) is used for the preparation of the compound of the formula (1) of the invention - the use of the compound. Compounds are used in the preparation formula (Π 12 201223934) The method of the present invention provides several advantages over the prior art. Importantly, the complete carbon architecture of the 4 ^ ^ ^ species is the use of two fragments of similar molecular weight at a single height ^ To construct. Compared with the more linear stepwise method (such as the square illusion disclosed in W〇98/45237 VIII), the total yield of the tiara process. In addition, due to the similar molecular weight: species: segment for the late stage of synthesis' It can be easily separated from the higher point of the formula (1) and the intermediate phase tb having a molecular weight similar to the final product in the CC bond forming step. The final product of this method is easier to purify and more easily aromatic. It is obtained in the form of a high aromatic purity, which is especially important for the products designated for use as a fragrance. This product is characterized by the extreme aroma sought by the fragrance industry. Abbreviations of the Examples and Raw Materials List of Heterohexane Heterohexanes THF Tetrahydrofuran quant. Quantitative, ie, 1% yield Example 1 At _5 ° C, the formula (π υ) compound (5 75 g, η min〇i)

Μ 13 201223934 in hexane, 24 mmol). The mixture was stirred at -50 ° C for 0.5 hours, and the compound of formula (IV-1) (4.7 ml, 3.8 g, 29 mmol) was added dropwise over 10 minutes.

(IV-1) Stirring was continued at -50 ° C for 0.5 hours, and then the temperature was raised to 〇 ° C in 0.5 hour. Water (60 ml) was added, the THF was evaporated, evaporated, evaporated, evaporated, evaporated, evaporated, evaporated. Compound.

Ch3 ch3 (Gl) ]U NMR (400 MHz, CDC13) δ 1.61 (s, 3H), 2.17 (dd, J = 8 Hz, 15 Hz, 1H), 2.29 (s, 3H), 2.36 (s, 3H) , 2.50 (dd, J = 3 Hz, 15 Hz, 1H), 3.19 (s, 3H), 3.30 (s, 3H), 4.14 (s, br, 1H), 4·18 (dd, J = 3 Hz, 8 Hz, 1H), 7.08 (m, 2H), 7.50 (m, 1H). Example 2 14 201223934 A compound of the formula (ΙΙ-l) prepared according to Example 1 (0·51 g, 2.14 mmol), acetic acid (2.7 ml), water (〇2 machine) and sodium acetate (〇5i The mixture was stirred at room temperature for 3 hours. The mixture was diluted with water, basified to pH &lt;7&gt;7 by addition of solid NaHCCh and then extracted with EtOAc. The combined extracts were washed with brine and dehydrated (MgS〇4) And concentrated under reduced pressure to give a compound of formula (!): </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; δ 2.16, 2.18, 2.22, 2.31, 2.45 1 (5 xs, 9H), 5.94 and 614 (2 X d, J = 8 Hz, 1H), 6 93 (m, 1H), 7.12 (m, 2H), 9.22 And 10.16 (2 xd, j = 8 Hz, 1H). Example 3 LiCl (0.62 g, 15 mmol) and 1/5 formula (ΙΙΙ_1:) compound (loo% (in-ι) compound amount is ug , 5 4 mm 〇 1) was added to a suspension of magnesium (〇·19 g, 7.8 mmol) in THF (2.5 ml). The mixture was stirred at 40 ° C for 1 hour' and the residual formula was added (ΠΙ_丨) compound and THF (12 ml). When most When dissolved, the mixture was cooled to Ό -35 ° C ' and a solution of the compound of formula (IV-1) (1.0 nU, 6.2 mmol) in THF (1 ml) was added. The mixture was stirred at -40 ° C for 1 hour. , warmed to -1 0 C ' and added a saturated aqueous solution (1 〇mi). Evaporate THF ' under reduced pressure and extract the residue with toluene (3 X 3 0 ml). The product was dried (MgSO.sub.4) and concentrated under reduced pressure. &lt;1&gt;H NMR of the residue showed that the product mixture contained 5 to 10 wt% of compound of formula (II-1). Example 4 15 201223934 Formula prepared according to Example 1 (ΙΙ- l) A mixture of the compound (0.51 g, 2·14 mmol), THF (7 ml) and aqueous hydrochloric acid (32%, 12 ml) was stirred at 60 ° C for 2 hours and at room temperature for 3 days. (20 ml) The mixture was diluted and concentrated under reduced pressure to give 0.4 g of compound of formula (I) as oil. The 1H NMR spectrum indicated that the oil was a 3:1 mixture of two stereoisomers. Brief description] No [Main component symbol description] No 16

Claims (1)

201223934 VII. Patent application scope: 1. A compound of formula (I), The double bond labeled with (a) has a (Z) or (E) configuration, and a mixture of the E-isomer and the Z-isomer. 2. A method (A) for preparing a compound of the formula (I), wherein the formula (A) is as defined in the first item of the patent application, and the method (A) comprises a compound of the formula (A) and an acid (a) The reaction in the presence of water (A); Wherein Q R1 and R 2 are the same or different and independently of each other are cm alkyl groups, or R 1 and R 2 are bonded to each other and are represented by a group, thereby linking R 1 and R 2 to the two emulsions and connecting the two oxygens The C atom of the atom forms a five- or six-membered ring; the acid (A) is selected from the group consisting of w, _ ^, . Cl-4, acid-lowering acid, C2-6 dicarboxylic acid S?, king emulsified C2-4 monoacid, Perfluorinated r C2-4 monoterpic acid, oleic acid, hanging toluenesulfonic acid, methanesulfonic acid, sulfuric acid, when, and sub-exchange resins and mixtures thereof. The method of claim 2 (A)' wherein the acid (A) is 17 201223934 trichloroacetic acid, free formic acid, acetic acid, hydrochloric acid, p-toluenesulfonic acid, fat and The mixture is made of propionic acid, butyric acid, acid, sulfuric acid, and group. a method (A) of trifluoroacetic acid, and an acidic ion exchange tree, wherein 'the solvent (A) is selected from the group consisting of 1 to 4 and a mixture thereof. 4, as in the scope of claim 2 or the reaction (A) In the solvent (A), tetrahydrofuran (THF) and acetonitrile 'propionitrile' c group were carried out. 5 · If you apply for patent scope 2 to r A, Gan a · gentleman, drink one or more methods (A ) ' each of which (a) is THF. 6. If the scope of patent application is 2, the method of one or more of 5 乐 music 5), the middle reaction (Α) is carried out in the presence of salt (Α); sleep (phantom is independent of acid (4), is derived from Acid (Α) is a salt; wherein the acid (A) is as defined by 4, Fuxi and AJ are as defined in the second paragraph of the patent scope of the application. The method of the flute &amp; tS 丄 2 2 2 ～ 2 ～ 6 6 6 6 6 6 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 The compound of the formula (II), 豆·兮γττ, η λ 豆 Τ 式 式 式 式 式 式 式 式 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 Wherein the compound of the formula (π) is as defined in the second item of the patent application, the method (B) comprises the reaction (B) in the dissolution &quot;B), the reaction (B) comprising three consecutive steps (a) , (b) and (c), which are all carried out in the solvent (B); the step (a) is a reaction of the compound of the formula (ΠΙ) with a reagent (Bal) (ai ); 18 201223934 Wherein R3 is a lignin_ · reagent (Bal) # @ ό Λ p ” is selected from the group consisting of _C 4 alkyl magnesium, Cw alkyl lithium, sodium naphtha, inscription, rheme or H; '&quot;(b) is a compound of the formula (IV) and a reaction of the reaction of the step (a). (IV) ?人? R1 R2 wherein R1 and R2 are as defined in item 2 of the patent application; step (c) is a mixed reagent (Bc) and a reaction mixture produced by the step (b); the reagent (Bc) is Water, Ci4 alcohol or a mixture thereof; The agent (B) is selected from the group consisting of benzene, toluene, diphenylbenzene, hexane, cyclohexane, 6-4 alkylcyclohexane, heptane, THF, di-Ci4 alkyl ether, methyl-THF, i, a group consisting of 2-methoxyethane, 1,4-dicropin, (14) a trialkylamine and mixtures thereof; step (b) is carried out directly after the reaction (al), or in the reaction (a) Thereafter, and before the step (b), the reaction (a2) is carried out by adding the reagent (Ba2) to the reaction mixture produced by the reaction (a1); the reagent (Ba2) is selected from the group consisting of Zn, Abu Ca, Zr And/or Ti toothing, c _4 alcoholate and mixed halide Ci_4 alcoholate and mixtures thereof composition 19 201223934 group 9 method (B), wherein R3 is Br. 9 or 10 Method (B) 'where, gasification of isopropyl town, n-butyl clock, ίο. as claimed in the scope of the invention 11. For example, the patent scope of the reagent (Bal) is sodium, money, Ming Dibutyl clock or Third butyl lithium. 12 士申# Patent 1a, paragraphs 9 to 11 of the method or method (B), wherein the reagent (Bc) is water. 13 'If the application of the month of the patent range ninth To one of the nth or a plurality of methods), wherein the solvent (Β) is selected from the group consisting of benzene, toluene, xylene, hexane, % hexane, methyl hexane, heptane, THF, diethyl ether, dibutyl ether, methyl _THF, ' Methoxy ethoxy, 1,4 哼 哼, triethylamine and mixtures thereof, such as A, please apply one or more of the second to seventh items of the patent scope to the first / the formula (Π The compound has been prepared by the method (B) of the above-mentioned patent scope item - or a plurality of methods. The use of the compound of the formula (1) as a fragrance compound is as set forth in the first item of the patent scope. Definition: Formula (16.-type (Π) compound use, its use.] Hai (II) compound is as claimed in the scope of the patent ^ (I) The compound of the formula (I) is as claimed in the patent scope] The use of the 17' species (ΠΙ) compound defined in the item, the basin is used for the definition. The compound, the formula (5)), the compound is as defined in the patent specification, the formula (8) is the patent application蠤20 as defined in 9 items