PL97720B1 - METHOD OF MAKING PHARMACEUTICALLY ACTIVE NEW ALPHA-SUBSTITUTED BENZHYDROL DERIVATIVES - Google Patents

Description

The patent description was published: October 16, 1978 97720 MKPC07c 31/14 C07c 33/06 Int. Cl.2 C07C 31/14 C07C 33/06 Inventor Patent holder: Richter Gedeon Vegysszeti Gyar RT Budapest (Hungary) READING ROOM Ur ^ du Pulewlg * Process for the preparation of pharmaceutically active, α-substituted benzhydrol derivatives The present invention relates to a process for the preparation of new, α-substituted benzhydrol derivatives, their acid addition salts and quaternary ammonium salts. The new compounds according to the invention have the general formula 1, in which Z is an ethyl or vinyl group, Rt and R2, identical or different, denote hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, trichloromethyl groups, nitro, nitrile, hydroxyl, alkoxy, 1-6 carbon atoms, amino groups or aminoalkyl groups 1-4 carbon atoms, aLkylamino groups 1-6 carbon atoms or optionally esterified mercaptan groups, R8, R4 and Rs, which are identical or different, denote hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, cycloalkyl groups containing up to 7 carbon atoms, aralkyl groups, containing 1-4 carbon atoms in some parts alkyl groups, phenyl groups, trihalomethyl groups, nitro groups, nitrile groups, hydroxyl groups, alkoxy groups containing 1-6 carbon atoms, carboxyl groups or optionally acylated amino groups or aminoalkyl groups containing 1-4 carbon atoms, alkylamino groups containing 1-6 carbon atoms, dialkylamino groups containing 1-6 carbon atoms, which, optionally with the inclusion of an adjacent nitrogen atom, can form a maximum of 2 8-membered rings, optionally containing also oxygen or further nitrogen atoms and optionally substituted with alkyl of 1-4 carbon atoms, alkylaminoalkyl group containing 1-4 carbon atoms in each alkyl portion, dialkylaminoalkyl group containing 1-4 carbon atoms in each alkyl portion, optionally including of the adjacent nitrogen atom may form a maximum of 8-membered ring, possibly also containing oxygen or other nitrogen atoms, a dialkylamino group with 1 to 4 carbon atoms in each alkyl part, optionally esterified or etherified mecaptan groups or optionally etherified hydroxyl groups, and when Z is an ethyl group, not all Rlt, R2, R8, R4 and R5 are simultaneously hydrogen and not all simultaneously methyl; if Rt, R2, R8 and R4 are hydrogen, then R5 has a different meaning than amino in 2- or 4-position, dimethylamino in 2- or 4-position, 1-pyrrolidinylmethyl in 2-position, bromine, methyl or methoxy in position 4; if R1, R2 and R8 are hydrogen, then R4 and R5 have meanings other than 2,4-dimethoxy or 3,4-dimethoxy; if Rj and R2 are hydrogen, then R8, R4 and R5 have different meanings than 2,4,5-or 2,4,6-trimethoxy, 4-methoxy-3,5H-dimethyl or 2-amino-3,5 -doubletrom; and for the case of 97 72097 720 when Z is vinyl, if R1, R2, R3, and R4 are hydrogen, then R5 has a different meaning than the 4-methyl group or a hydrogen atom. In the above definition H1f R2, Rs, R4 and R5 "halogen" denote any halogen atom, such as, for example, fluorine, chlorine, bromine or iodine. Straight or branched chain saturated or unsaturated low alkyl groups preferably have from 1 to 6 carbon atoms. groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tertiary-foutyl, amyl, isoamyl, hexyl, isohexyl or vinyl, allyl, propenyl, butenyl, pentenyl , hexenyl, propargyl, etc. Most preferred are methyl, n-butyl and 1-tert-butyl. The cycloalkyl group preferably has 5-10 carbon atoms and consists of one or more rings, for example cyclopentyl, cyclohexyl, cycloheptyl. but ^ especially a cyclopentyl group. The aralkyl group contains 7-20 carbon atoms and consists of one or more rings. Preferably, the arylalkyl group has a low alkyl group and one or more rings. Examples include, for example, benzyl, phenethyl, phenylpropyl, phenylbutyl, naphthylmethyl, naphthylethyl, naphthylpropyl, and naphthylbutyl. However, the benzyl group is most preferred. As aryl groups are aromatic hydrocarbyl groups of 6 to 14 carbon atoms, consisting of one or more rings, for example phenyl, diphenyl, naphthyl and especially phenyl groups. The trichloromethyl may contain any of the above halogen atoms. Most preferably, the trihalomethyl group is a trifluoromethyl group. The hydroxyalkyl group may contain any of the above-mentioned alkyl groups. Both the hydroxy and also the hydroxyalkyl groups may optionally be esterified or terriated. An esterified group is, for example, a hydroxyl group acylated with an acyl group of an aromatic or aliphatic carboxylic acid. The acyl groups of aliphatic carboxylic acids are, for example, acyl groups of monobasic saturated carboxylic acids, for example formic acid, acetic acid, pro - vertical, butyric, valeric, etc. In addition, there are acyl groups of unsaturated, monobasic carboxylic acids, for example acyl groups of acrylic, crotonic, vinylacetic, methacrylic acid, etc. The acyl group of an aromatic acid means, for example, the acyl group of benzoic acid, diphenylcarboxylic acids or naphthoic acids. The etherified hydroxyl group is preferably a low alkoxy group which has as the alkyl moiety each of the above-mentioned alkyl groups, in particular a methoxy or ethoxy group. The carboxyl group is esterified with an aliphatic or aromatic alcohol, if appropriate. for example methanol, ethanol, n-propanol, n-butanol, isobutanol, pre-butanol, pentanols, hexanols, benzyl alcohol, phenethyl alcohols, etc. The aminoalkyl group may contain any of the above-mentioned alkyl groups and it may optionally be acylated with one of the acyl groups mentioned above. Optionally, the amino group may be acylated with one of the acyl groups given above. For example, an N-benzoylamino group is preferred. The alkylamino, dialkylamino, alkylaminoalkyl and dialkylaminoalkyl groups, which contain low alkyl groups where appropriate, may include any of the above-mentioned alkyl groups, in particular ethyl groups. These groups can, optionally with the addition of an adjacent nitrogen atom, form a ring of up to 8 members, possibly also containing an oxygen atom or further nitrogen atoms. As such ring groups are suitable, for example, the pyrrolidine group. piperidine, perhydroazepinyl, pyrazolidine, imidazolidine, piperazine, hexahydropyrimidine, hexahydropyridazinyl, hexahydriazepinyl, axazolidine and morpholino group substituted with a merceridinyl group, especially with an acetic acid piperidinyl group. with alkyl groups. A preferred representative of these groups is, for example, methyl mercaptan. The compounds of general formula 1 have valuable pharmacological properties. They act to inhibit or induce the microsomal enzyme system of the liver, which affects the metabolism of foreign substances 45 and is therefore used in pharmacy. Particularly active representatives of the novel inhibitory compounds for the micro, mixed oxidase system are, for example, 2-methoxy-a-ethylbenzhydrol, 2,4-dimethoxy-a-vinylbenz-hydrol and 4- (a-diethylaminoethoxy) -a-ethylbenzhydrol. The braking is long-lasting and also after 48 hours from the moment of administration Due to the action of these compounds, the metabolic activity of the liver is lowered in relation to substances of external origin, for example drugs, steroids, etc., thereby prolonging the period of presence and action of these substances of external origin in the body. For this type of pharmaceutical use, the β-2-diethylaminoethyl-α, α-diphenylvalerate (Proadifene) has been regarded as the most active substance until now. The new compounds produced by the method according to the invention significantly exceed its efficiency and duration of action. With the use of the new compounds, the activity of the enzyme system does not increase even after the inhibitory effect ceases, as is the case with (2-diethylaminoethyl) α, α-diphenylvalerate. In a combination of drugs, the duration of action of the active ingredient can be prolonged by the use of the new compounds. The enzyme inhibitory efficiency of the new compounds was determined in vivo by measuring the oxidase activity on hexobarbital. Female Wistar rats weighing 80-100 g were orally administered a single dose of the compounds to be tested in the amount of 0.3 mmol / kg. After 24 or 48 hours after treatment, the rats were anesthetized by intravenous administration of sodium hexobarbital 15 in an amount of 40 mg / kg and the time to complete awakening was measured, for example, J. Noordhook: Eur. J. Phanmacol. 3, 242 (1968). The mean value of the group, the standard error and the percent deviation from the control were determined. The change in sleep time indicates that, due to the action of the enzyme inhibitory compounds, the hexobarbital breaks down more slowly in the body into biologically inactive metabolites. Measurement of the serum hexobarbital concentration at the time of awakening of the rats was found to have no interaction with the central nervous system, e.g., A. Jori, A. Bianchetti, P.E. Prestini: Biochem. Pharmacol. 19, 2687 {1970), as the determined value does not differ from that measured in control rats. 30 The test results are presented in Table 1, where the following abbreviations were used: E 16 = 2-methoxy-α-ethylbenzhydrol E 17 = 4- (P-diethylaminoethoxy) - hydrol. Table 1 Substance E16 E17 Proad- ¦ itfen control Deviation in the sleep time of the treated rats from the sleep time of the control rats hours 2 +: 43 + 109 +1175 24 +, 43 Hi 28 -338 48 +46 +33 -39 Concentration and wake-up factor ug / 100 ml ( 48 hours) 7.1: ± 0.83 7.6 ± 0.90 41 + 1.0 7.3 ± 0.92 Prolongation of the sleep time and durability of the action, as also after 48 hours the action still exists, indicate that the compounds E16 and E17 permanently inhibit the secretion and inactivation of substances of external origin in the liver. The quality of action of the new compounds is also better than that of Proadiphene used as reference substance, since after the initial inhibitory action with the compounds of general formula I, there is no phase with increased "detoxicating" activity, which is the case in the case of Another group of new compounds according to the invention have an enzyme inducing effect, and these substances also have wide pharmaceutical applications, for example for the treatment of jaundice in newborns. The essence of jaundice in newborns is that after birth, the relative amount of the enzyme linking bilirubin with glucuronic acid (UDP glucuronyltransferase; EC * 2.4.1.17) is too small to be associated with the glucuronic acid of free bilirubin in the plasma from the breakdown of red cells and free bilirubin is not secreted from the spine nor in the urine, but it is constantly circulating and causes jaundice. Free, fat-soluble bilirubin is also bound by the central nervous system, where it interferes with cell respiration. It is also the higher content of bilirubin that can lead to irreversible damage and possibly death. Serum bilirubin levels rise to varying degrees in newborns. The number of infants at risk, however, is high and tends to increase, which is mainly due to an increase in the number of premature babies, to incompatibility of blood groups (ABO, RH) and to deliveries with tissue hypoxia. Therapeutic research is being conducted all over the world to prevent and treat jaundice in newborns. However, the most commonly used phenobarbital so far is dangerous because of its toxic side effects, namely the paralysis and paralysis of the respiratory system, and therefore there is a growing interest in more beneficial compounds. The compound used for treatment must have a strong induction effect on the microsomal enzyme system of the liver and This method accelerates the combination of bilirubin with glucuronic acid. The compound must be such that it can be administered to the newborn from the first day of life, it must also be active when administered orally, must have an inducing effect after administration of one the dose and action of the compound should be rapid. A further essential requirement is that the compound to be used has no or only a slight different pharmacological effect and that its toxicity should be low. It is especially important that the compound does not affect the central nervous system, the endocrine system and the immune system, because these body systems in the first ectopic days are particularly sensitive and react to certain pharmaceutical agents with irreversible changes. according to the invention, in particular, 3-chloro-α-ethylbenzhydrol, 3-tr6-fluoromethyl-α-ethylbenzhydrol, 2,5-dimethyl-α-ethylbenzhydrol, 2-ifluoro-α-α-ethylbenzhydrol, -vinylbenzhyidrol and 2,4-97 720 -dichloxo-α-ethylbenzhydrol. Sometimes these compounds correspond to the action of phenobarbital and their potency, but unlike phenobarbital, the new compounds do not show an effect on the central nervous system, while phenoberbital has a calming and paralyzing effect. The new compounds increase the activity of an enzyme in the liver that transforms "detoxifying" substances of external origin, for example, they increase the activity of gluteironyltransferase and thus the combination of bilirubin with glucuronic acid and the secretion of bilirubin from the circulation. of newborns, but they can also be used to treat hyperbilirubinemia of other origins.These compounds accelerate the regeneration of the liver, and are also suitable for the rapid removal from the body of substances derived from environmental pollutants and accumulated in the body, in the first place of insecticides. In the case of disease symptoms associated with the overproduction of steroid hormones, it is possible to obtain continual deactivation of the steroids by repeated administration of the inducers. In animal experiments it has been found that the new compounds produced according to the invention increase the deactivation of the progestin, which may be assumed although in combination with estrogen they are suitable for the prevention of pregnancy. The strength of the enzyme-inducing action has been determined in various ways. In the first row, the in vivo oxidase activity was measured against hexobarbital. The method of this measurement has been described in greater detail above for inhibitory compounds. The reduction in sleep time is due to the fact that treatment with the compounds according to the invention accelerates the removal from the body of hex barbital used as a standard foreign compound. The effect of a single dose of the inducing compound on hexobarbital-induced sleep 24 hours after administration is shown in Table 2. The following abbreviations are used in Table 2: E 9 = 3-chloro-α-ethylQ-benzhydrol E 11 = 2,4-dichloro -a-ethylbenzhydrol E 15 - 3-trifluoromethyl-a-ethylbenzhydrol E 20 = 2,5-dimethyl-a-ethylbenzhydrol SE The method of determining the standard error 45 50 It follows from Table 2 that in an attempt to measure the oxidase activity, the action of the compounds of general formula I corresponds to that of phenobarbital. 24 hours after the pretreatment with inducers, the biological half-life of hexobarates was measured. bital, e.g. J. Noordhoek: Eur. J. Pharmacol. 3 242 (1968), relative concentration at awakening, with female rats weighing 150 g serving as experimental animals. The obtained results are presented in Table 3. Table 3 Control substance E 11 E 15 ti / 2 minutes 37 86+ 23+ on M-gAnl awakening, 8 0.8 ', 1 0.8 7.3 ± 0.9 The biological half-lives are significantly shorter (+) in the treated groups than in the control groups. The awake concentrations showed no difference. The compounds of general formula I thus greatly accelerate the disappearance of hexabirbital from the blood serum. At the same time, the same concentration at awakening proves that the new compounds do not affect the sensitivity of the central nervous system to hexobarbital, but their point of action is the microsomal enzyme system of the liver, which is induced by new compounds. 24 hours after pretreatment with compounds of general formula I, the biological half-lives of meprobamate, for example, B.J. Ludwig, A.J. Hoffman: Arch. Biochem. 72, 234 (1957), and the obtained results are presented in Table 4 Table 4 Control substance E 11 E 15 ti / 2 hours 4.0 2.8+: 2.1 + Table 2 Control substance 27.0 ± 1, OE 9 E 111 E 15 E 20 phenobarbital Sleep time in minutes ± SJE. | mg / kg 21.7 ± 2.0 22.0 ± 2.1 18.0 ± 1.7 23.8 ± i 1.9 2Q, 1 ± 2.0 mg / kg, 2 ± 1.4 16.4 ± 1, 6 14.2 ± 1.5 18.6 ± 1.9 14.3 + 1.4 mg / kg 13.6 ± 1.4, 0 ± 1.4, 6 ± ly2 14.0 ± i 1; 3 14.0, ± 1.3 40 mg / kg 12.4 ± 1.2 13.0 ± 1.2 », 8 ± 0.9 13.0 ± 1.2 12.5 + 1J29 Pre-treatment with compounds prepared according to the rate thus significantly accelerates the release of meprobamate . These compounds accelerate the conversion of tneprobamate into biologically inactive metabolites quite visibly. Serum bromosulfophthalein content 24 hours after treatment with the compounds according to the invention and intravenous administration of brosulftephthalein, for example E. Targa, E. Fischer: Acta Phisiol. Hung. 36, 431 ca 5 Table 5 Control substance E 9 E 11 E 15 E 25 phenobarbital Brornosulfophthalein fig / ml serum 16.9 7.6 * 4, 0, 1 6.9 Table 5 shows that the new compounds are as They increase the excretion of bromosulfophthalein to a greater extent than phenobarbital or to a greater extent. The increase in bromosulfophthalein removal is also evidence of an increase in detoxification capacity. In order to determine the UiDP glucuronyltransferase activity of the liver tissue in vitro, e.g. B.P.F. Adlard, R.G. Lester, G.H. Lathe: Biochem: Pharmacol. 18, 59 (1969), the liver tissues of untreated animals treated with compounds of general formula I were incubated in the presence of bilirubin and the content of glucuronic acid bound bi-lirubin was determined after incubation. The results obtained are shown in Table 6. Table 6 Control substance E 9 E 11 E 15 E 20 Bound bilirubin H & / g. at , 6 ± 2.1 36.7 ± 3.2, 7 ± 2.8 37.4 ± 3.6, 1 ± ^ 2.6% +: 43 +140 +.44 + i37 Table 6 shows that the compounds of the invention increase the capacity of the liver tissue to bind bilirubin to glucutonic acid. Bilirubin excretion has been studied in vivo in untreated and pretreated rats with E15 after intravenous administration of 30 mk / kg of free bilirubin, for example H. Krueger, J. Higginson: Proc. Soc. Exp. Biol. Med. 107, 43 (1961). The half-lives of bilirubin are given in table 7. 7 »Table 7 Substance 1 control E 15 phenobarbital thi / commune J 16 1 7 1 13 1 Table 7 shows that the compound £ 15 significantly accelerates bilirubin clearance in saezuras. Its accelerating deduction is true twice as much as that of phenobarbital. The toxicity of the new compounds is insignificant and much lower than that of phenobarbital used as reference substance. Phenarbital, despite its unfavorable properties, is used in the treatment of jaundice in and newborns. Table 8 lists the doses at which phenobarbital causes fatal respiratory shock. The results observed with the use of the same amounts of the new compounds are also shown in Table 8. Table 8 Phenobarbital substance E 9 E 11 E 15 Number of animals killed / total 40 1 liii 80 1 liff 160 4/10 0/10 0 / 20 0/10 300 liii | 640 mg / kg and from Table 8 it can be seen that the toxicity of the new compounds is much lower, and the therapeutic index is much more favorable than the toxicity and pharmaceutical index of phenobarbital. 45 The delivery of the novel compounds produced according to the invention to the central nervous system has been studied by the following methods: electroshock (E ^ A. Swinyard, WC Brown, LiS. Goodman: J. Pharmacol. Exp. Direct. 106, 319 (1952). ), subway shock 50 solo Exp. Ther. 81, 402 (1944), thiosemicarbazide shock (J; P. da Vanzo, MJE. Greig, MA eormin: Amer. J. Physiod. 301, $ 33 ^ 1961), strichin shock (TL Kerley, AG Richards, R * W. rBegley, 55 BB Abreu, LV W. sver: J. Pharmacol. Exp. Ther. 182, 360 (1961) nicotine shock (CA. Sfome, KL Mecklenburg, MN Torbans: Arsh. Int.: I? Har- macoi & yn. 117,419 <1 ^ 8) y rotary pset nard, CJ Carr: J. Pharmacol. Exp. -Tfoer. J & l, 60 354 (1957), Mortality Resist by physiostatic (T. Nose, M. Kojima: Europ. J. # 1 ^ rmaepj. 0, 83 (1970), potentiating action of ijiifein ^ * M. Quintin: Brit. J. Pharmacol. 21, 51 (1963), Pain Relief (C. Bianehini, J. France Schini: Brit. J. Phann. Ctemotber. <9, 280 (1954). 12 As reference substances were phenobarbital. Phenobarbital and the new compounds were administered orally in doses of 40 mg / kg, 120 mg / kg and 150 mg / kg. In the experiments carried out according to the above methods, the new compounds in the doses specified did not work, while phenobarbital was already in the dose of 40 mg. / kg has a strong anticonvulsant effect, distracts muscular contractions and has a calming effect. The new compounds produced according to the invention therefore have the advantage that, unlike phenobarbital, they do not have any effect on the central nervous system. Pharmaceutically active new a-substituted benzhydrol derivatives produce According to the invention, the benzophenone of the general formula II, in the form Rlt R, R, R4 and R5 have the above meanings, reacted with an ethylmagnesium halide or with a vinylmagnesium halide, and the Grignard Jinplex compound is decomposed. and separating the obtained compound of general formula I, and the resulting products are optionally converted into acid addition salts or into quaternary ammonium salts, and or, if the product is obtained in the form of an acid addition salt, it is converted, if necessary, to a base oil and / or to a quaternary form of an alkaline base. A preferred form of the preparation of the new compounds is that the benzophenone is Formula II is reacted with an ethylmagnesium or vinylmagnesium halide, in particular ethylmagnesium bromide or ethylmagnesium iodide or vinylmagnesium bromide or vinylmagnesium chloride in the presence of an anhydrous organic solvent. The Gringnard reagent is used in the least equimolar amount. The reactions are preferably carried out in a proton-free organic solvent, for example in phthyclic ethers such as tetrahydrofuran or dioxane, in aliphatic ethers such as ethylene glycol dimethyl ether. Ethylene glycol, diethyl ether, di-n-butyl ether, and aliphatic or aromatic hydrocarbons, such as ligands, toenzene, toluene, xylene or mixtures of the solvents mentioned. The temperature during the reaction is kept between -10 ° C and the boiling point of the solvent used, preferably between -10 and 100 ° C. Upon completion of the reaction, the Grignard complex is decomposed with a dilute mineral acid, for example sulfuric or hydrochloric acid, or preferably with an aqueous ammonium chloride solution, and the compound of general formula 1 formed is separated. The product is purified by distillation or crystallized. The compounds of the general formula I can, if necessary, be converted in a known manner into acid addition salts or into quaternary ammonium salts. Low-alkali or low-alkenyl halides are used for quaternizing. straight or branched chain; and benzyl halides. Straight chain alkyl sulphates can also be used. The reactions are carried out in a solvent, for example acetone, ethanol or aeetonditrile at the boiling point of the solvent or under increased pressure at elevated temperatures. Used as starting materials. The compounds of the general formula II are prepared by methods known from the literature, for example by the Friedel-Craits method for the synthesis of knots. The pharmacologically active compounds prepared according to the invention can be used in the form of medicinal preparations in medicine. The medicinal preparations are prepared by converting the new compounds into forms suitable for use together with organic or inorganic, solid or liquid, physiologically inert adjuvants and carriers. The preparations can be administered enterally, parenterally or locally. The carriers used are substances which do not react with the new compounds. Suitable carriers are, for example, water, alcohol, gelatin, propylene glycol, vegetable oils, cholesterol, starch, milk sugar, talc, gum, magnesium stearate and all other carriers. used in pharmacy. Preparations can be sterilized. In addition, medicinal preparations can contain other auxiliary substances, for example, preservatives, wetting and emulsifying agents, stabilizers, dissolving agents, salts suitable for changing the osmotic pressure or buffers and other pharmaceutically valuable substances. by methods. To prepare injectables, the new compounds in the form of acid addition salts or quaternary ammonium salts are dissolved in physiological saline free of fever-causing substances or in double distilled water, the solution is optionally sterilized and then filling it into sterile ampoules. The production method according to the invention is explained in more detail by the following examples, without limiting its scope. EXAMPLE 1 The preparation of 2-amino-5-chloro-α-ethylbenzhydrol consists in preparing from 9.7 g of magnesium turnings and 38 to 15 g of ethyl bromide in 115 ml of anhydrous ether of ethylmagnesium bromide. A solution of 23.2 g of 2-amino-5-chlorobenzophenone in 350 ml of anhydrous ether is added dropwise to the cooled solution of Grignard compound, taking care that the temperature does not rise above -5 ° C. The reaction mixture is stirred for an additional 30 minutes at 0 ° C. After the completion of the reaction, which is checked by thin-layer chromatography, the reaction mixture is poured into a solution of ammonium chloride in ice-cold water. The ethereal phase is washed first with sodium chloride solution, then with water until neutral, then dried over sodium sulphate. After the ether has been distilled off, 18.3 g of 2-amino-5-chloro-α-ethylbenzhydrol are obtained, which crystallizes from n-heptane. Melting point: 91.5 ° -92 ° C. 91 129 13 14 Analysis for C 15 H 16 ClNO: calculated: C 68.83% H 6.16% Cl 13.55% N 5.35% Found: C 68.70 % H 6.21% Cl 13.52% N 5.18% Characteristic bands of the IR spectrum at 700, 760, 820, 885, 3280 and 3400 cm "1. UV spectrum: fcgjgj1 215, 250, 370 mm As described in Example 1, but with the use of appropriately selected starting materials, the following compounds are obtained: 4-phenyl-α-ethylbenzhydrol melting point: 100-101 ° C analysis for C21H20O: calculated: C 87.46% H6. 99% found: C 87.51% H 7.08% characteristic bands of the IR spectrum at 700, 765, 775, 835, 3560 cm -1. UV spectrum: X ™ E * 257 nm. 4-cyclopentyl-α-ethylbenzhydrol, boiling point: 180-182 ° C (0.2 Torr, C20H2 analysis): calculated: C 85.66% H 8.63% found: C 85.61% H 8.42 % characteristic IR spectrum band at 700, 760, 830, 2880, 2960, 3480, 3570 C "1. UV spectrum: X4 ™ 222, 254, 259, 265, 273 nm. 3-Amino-4-ipiperidine Ha-ethylbenzhydrol o melting point 103 104 ° C analysis for C20H26N2D: calculated: C 77.38% H 8.44% N 9.03% found: C 77.49% H 8.70% N 8.95% characteristic IR spectrum bands at 705, 760, 805, 880, 2820, 2940, 3300, 3370, 3460, 3580 cm -1 UV spectrum: X g ** 1 221.296 nm. 4-cyano-α-ethylbenzhydrol mp: 81.5-> 82.5 ° C analysis for C 16 H 14 NO calculated: C 80.96% H 6.37% N 5.90% Found: C 81.40% H 6.24% N 6.00% characteristic IR spectrum bands at 705, 760, 840, 2240, 3540 cm "1 UV spectrum: X gjgf 242 nm. 3-amino-4-moTfolin-α-ethylbenzhydrol melting point : 136-137 ° C analysis for C13H13N10O6 calculated: C 83.04% H 7.74% N 8.97% Found: C 73.14% H 7.80% N 9.00% characteristic bands IR spectra at 705, 775, 810, 875, 2820, 3300, 3380, 3440 cm "1 UV spectrum: X 2 * 297 ran-3-amino-4-chloroxo-α-ethylbenzhydrol, melting point: 103 ° C analysis for C15HltfClNO calculated: C 68.83% H 6.16% Cl 13.55% N 5.35% found: C 69.01% H 6.18% Cl 13.68% N 5.17% characteristic bands IR spectra at 700, 760, 800, 870, 3220, 3320 cm -1, UV spectrum: X 1 218, 297 nm. 3-Amino-4- (N, N-di-butylamino) -α-ethylbenzhydrol mp: 83-84 ° C analysis for CH 2 H 2 H 8 O: calculated C 77.92 *% H 9.67% N 7.90% found: C 77.87% H 9.61% N 7.92% characteristic wddma bands IR psnzy 700, 760, 830, 890, 2810, 2870, 2960, 3300, 3450, 3390 cm "1 UV spectrum : X2 ™ 298 nm. 4- (2-Methoxyethyl) -α-ethylbenzhydrol analysis for C1 H8HOJ: calculated: C 79.96% H 8.20% found: C 8040% H 8.16% characteristic IR spectrum bands at 700, 760, 1110, 3500 cm-1 UV spectrum: X JJJ ™ 259, 263, 273 nm. 3-amino-4- (N-methylpiperazine) -a-ethylbenzhydrol, mp: 154-155 ° C analysis for C20H27N4O: calculated: C 73, ai% H 8.36% N 12.91% found: C 73.75% H 8.38% B 13.03% characteristic IR spectrum bands at 705, 765, 815, 885 , 2830, 3260, 3350, 3440 cm-1 UV spectrum: X ™% ™ 297 nm. 4-morpholinomethyl Ora-ethylbenzhydrol mp: 96-96 ° C analysis for CMH2NO2: calculated: C 77.13% H 8.09% N 4.50% found C 77.24% H 8.20 % N 4.56% characteristic IR spectrum bands at 700, 760, 865, 1110, 2820, 3460 cm -1 UV spectrum: X EtOH 255, 260, 264 (inflection point), 270 (inflection point) nm. 2-methyl-α-ethylbenzhydrol, boiling point: 109-113 ° C / 0.05 torr. Analysis for ClftHl80: Calculated: C 84.91% H 8.02% Found: C 84.76% H 7.89 characteristic% of the KR spectrum at 700, 750, 770, 3500 cm "1 UV spectrum: X4 f 211, 259, 265, 272 nm. 4-benzyl-α-ethylbenzhydrole, boiling point: 172-176 ° C.) 0.1 tor analysis for C ^^ O: 40 calculated: C 87.37% H 7.33% found: C 87.56% H 7.34% characteristic bands of the IR spectrum for 700, 745, 760, 850, 3460 , 3570 cm -1 UV spectrum: X 16 f 224, 254 nm. 45 4-methylthio-α-ethylbenzhydrol, boiling point: 148- ^ 152 ° C / 0.1 Torr analysis for C16HlgOS: calculated: C 74.3tf% H 7.02% S 12.41% found: C 74.19 % H 7.13% S 12.32% 50 3-trifluoromethyl-α-ethylbenzhydrol analysis for C 11 H 2 F 2 O: calculated: C 68.65% H 5.39% F 20.34% found: C 68 , 55% H 5.42% F 20.18% characteristic bands of the IR spectrum at 700, 800, 55 760, 1080, 1120, 1170, 1320, 3400 cm -1 UV spectrum: X1 fj1 259, 265, 271 nm. 2-trifluoromethyl-α-ethylbenishydrol, boiling point: 91-94 ° C / 0.15 rt 60 analysis for C 5 H F / D: calculated C 68.56% H 5.39% F 20.34 % found: C 68.64% H 5.44% F 20.27% characteristic bands of the IR spectrum at 700, 750, 770, 1000, 1130, 1160, 1310, 3500 cm "and 65 UV spectrum: X 5} _ _ ? 215, 260, 266, 273 nm.nut # -ti * Jfluorwn "ityl -" - * "tylobenzhydrol at temperature ** wrtftttia: IM — OiWC / US Torque analysis for C19H ^ F / 3: calculated: CW $ 1 % H 5.30% F 20.34% found: C 68.61% H 5.55% F 20.28% characteristic bands * IR spectrum at 700, 760, 835, 1070, 1120, 1170, 1025, 3400 cm "1 UV spectrum: X gg1 21 *, 252, 259, 264 nm. 2.3.4 → 5.6% polyethylene) ro-a-eitylbenzhy4 (roll, boiling point: 8 ° - & 4 ° C / Q The following analysis for dfHuFgP: calculated: C 50 £ 1% H 3.67% F 31.43% found: C 50.80% H 3.38% F 31.50% characteristic IR spectrum bands at 700, 760, 990.3400 cm'1 UV spectrum: X ^ g1 259.264 nm.2,4-Dichloro-mtHrtyVbenashydrol, boiling point: 136-138 ° C / 0.1 tora analte for d * HuC ^ P: calculated: C 64 , 07% H 5.02% Cl 25.22% Found: C 64.21% H 5.13% Cl 25.41% characteristic bands of the ER spectrum at 700, 770, 880, 1050, 1006, 3500 cnr1 wldmfc tIV: 1 sjg1 254, 259, 264, 280 nm, 3-iodo-α-ethylphoenzhydrrol with boiling point: WD-4a # C / W there analysis for C12H2JO: Bikrzoao: »C 53.3 6% &lt; 4.47% J 37.52% Found: C 53.11% H 4.74% J 37.44% chairaikitic bands of the IR spectrum at 700, 765, 785, 3400 cm &lt; &quot; &gt; 1 UV spectrum: l ™ ° ? 258-258 nm. S-cWbrib. Het, 1MVlhydtol, bp: 124-125 ° C / 0.02 tare analysis for C11HmClIG; tfH * cz found: C 72.87% H 6.28% Cl 14.36% characteristic bands of the IR spectrum at 695, 700, 740, 785, 1075, 3400 cm " 1 spectrum: UV: X &lt; &gt; H 255, 259, 274 µm 2-fluoro-ethyl acetate, melting point: 52.5 ° 53.5 ° C analysis for C 15 ° H 2 ° C: calculated: C 78.23% H 6.57% F ≤ 25% found: C 78.39% H 6.75% F 8.25% characteristic bands of the IR spectrum at 700, 760, 770, 3500 cm-1 UV spectrum: X 'JJgf 262, 268 nm. 2-chloro-a-elylobe (N-Hydrol, mp: 50.5-51.5 ° C, analysis for CH2H210: calculated: C 73.03% H 6.13% Cl 14.37% found: C 73.00% H 6.21% Cl 13.39% characteristic bands of the IR spectrum at 700, 750, 760, 3350 cm "1 40 45 50 55 UV spectrum: X EtOH and max 254, 259, 265 nm. 4-fLuoro-α-ethylbenzhydrol at temperature September: 135-137 ° C / 5 Torr. Analysis for CH 2 H 2 FO: calculated: C 78.23% H 6.57% F 8.25% found: C 78.26% H 6.29% F 8. 42% characteristic band of the IR spectrum at 700, 760, 830, 3500 cm-1 4 -chloro-α-ethylbenzhyde (rQl with weighing temperature: 53-a55 ° c / o, 3 dl analysis a CUH ^ CKD: calculated: C 73.02% H 6.13% Cl 14.37% found: C 72.84% H 5.84% Q 14.49% characteristic IR band at 700, 765, 830, 3500 cm "1 witiDto JJV: k ™ °? 223, 254, 259, 275 nm. calculated: C 71.50% H 7.33% 3 ^^ wucJilO! rx) -a-ethylbenzhydrol, boiling point: 140-h142 ° C / 0.1 tor analysis for C15H14Cl2O: calculated: C 64.07% H 5.02% Cl 25.22% Found: C 64.22% H 5.13% Cl 25.11% characteristic bands of the IR spectrum at 700, 755, 825, 880, 1070, 3400 cm -1 UV spectrum: X gjg1 258, 264 272, 281 nm, 3,4,5-trimethoxy-α-ethyllabenzhydrol, mp: 123-124 ° C analysis for C18HM04: calcd: C 71.50% H 7.33% found: C 71.41% H 7 ^ 18% characteristic IR spectrum bands at 705, 760, 835, 855, 1010, 1130, 1140.3460 cm -1 UV spectrum: Jt.JgJ1 213, 268, 273 nm. 4-III-t4 * -butyl-o-thiobenzhydrol boiling point: 148-150 ° C / 0.4 tq. Analysis for C18H240: calculated: C 85.02% H 9.0 (1% found: C 34.84% H «44% characteristic IR bandwidth burns 700, 765, 830, 5450 cm-1 UV spectrum: X EtOH 258, 263 nm. 4-Cryxy-1-ethyl benzhydrole melting: 125.5-129.5 ° C analysis for C ± filu09: calculated: C 74.98% H 6.29% found: C 75.12% H -6.41% characteristic spectral bands 850, 1670, 2400, 3200, 3540 cm -1 temperature UV spectrum: X EtOH 243 nm, m pEs 700, 760, temperature, UV spectrum: X EtOH 260, 265, 271 nm. 4-aminomethyl-3-erythylbenzohydrol mp: 97.5-98.5 ° C analysis for C16H19NO: calculated: C 79 , 63% H 7.94% N 5.80% Found: C 79.44% H 8.12% N 5.91% characteristic IR spectrum bands at 705, 770, 815, 2700, 3500, 3300, 3370 cm " 1 UV spectrum: X j ^ f 221, 260, 264 nm. 3-amino-a-ethylbenzhydrol analysis for C ^ ^ NO: calculated: C 79.26% H 7.54% N 6.16% found: C 79 , 28% H 7.71% N 5.99% characteristic bands of the IR spectrum at 705, 710, 760, 780, 3300, 3320, 3400, 3480 cm * 1 UV spectrum: X 2 H H (HCl) 253, 260 nm. 4-bromo-.alpha.-ethylbenzhydrol, boiling point: 140 ° C / 0.8 Torr. Analysis for C15HlsBxO: calculated: C 61.87% H 549% Boron 27.44% found C 62.06% H 5.25 % Br 27.45% characteristic IR spectrum bands at 700, 760, 820, 3500 cm "197720 in W: X EtOH W, max m, m 259, W ma. 2.5H-dimethyl-a-ethyl] obenzhydrol melting point : 38-30 ° C analysis for GtfEyO: calculated: G 84.95% P 8.39% Found: G 35.10% H 8.59% characteristic bands of the IR spectrum at 700, 760, 820, 880, 3500 ohm " 1 wddttW XIV: l 5J2? 270, 278 nm. Example II. The preparation of 4- (p-diethylaminoethokBy) -alpha. Ethylbenishydrol is made from 3.8 g magnesium turnings and 17.44 g ethyl bromide in 60 ml anhydrous ether, Girignard's reagent cooled to - 10 ° C, a solution of 24 g of 4- (OH-dimethylaminoethoxy) benzophenone in 120 ml of anhydrous ether is added dropwise. The reaction mixture is stirred vigorously. The temperature was raised to 0 ° C and the mixture was stirred at this temperature for 30 minutes. The reaction mixture is then heated to reflux for 15 minutes. After completion of the reaction, which is verified by thin layer chromatography, the reaction mixture is poured into an ice-cooled aqueous ammonium chloride solution. . The ether layer is separated, the aqueous layer is shaken twice with ether using Tazem 60 ml of ether. The ethereal solutions are combined, washed until neutral, dried over magnesium sulphate and then the ether is distilled off. The solid residue recrystallizes from ethanol. Thus 18.1 g of product are obtained, mp 58-59 ° C. Analysis for C 12 H 8 8 NOa: Calculated: C 77.02% H 8.93% N 4.28% Found C 77.04% H 9. 17% N 4.11% characteristic bands of the IR spectrum at 700, 755, 830, 1030, 1250, 3150 cm -1 XJV spectrum: X 228, 275, 282 nm. By selecting the appropriate starting substances, the following is prepared in an analogous manner. ¬ impressive compounds: 4-n-butyl-α-ethylbenzhydrol, boiling point: 144-145 ° C / 0.1 torr. Analysis for C19H240: calculated: C 85.02% H 9.01% found: C 84.82% H 9.24% characteristic bands of the IR spectrum at 700, 760, 830, 3500 cm -1 UV spectrum: X 5 JE f 258, 264, 272 nm. 2-methoxy-.alpha.-ethylbenzhydrol, mp: 62-63 ° C analysis for CieH1802: calculated: C 79.31% H 7.49% found: C 79.50% H 7.27% characteristic IR spectrum band at 700, 745, 760, 1020, 1240, 3500 cm ", 1 UV spectrum: X 2 · 228, 275, 282 nm. The ethanol solution of 4 - ((3-divuethylaminoethoxy) -a-ethylbenzhydrol is treated with an ethanolic solution To this solution, cooled to -15 ° C, ether is added and the acid fumaran 4- (O-diethylaminojoethoxy) Hx-ethylQbenzhydrol is precipitated, filtered off, washed with ether and then dried. Melting point of the salt obtained: 108.5-h109.5 ° C. Example III. The preparation of ethylbronjica 4- (O-dimethylaminoethoxy) ethylbenzhydrol consists of 16.3 g of 4 -) ( pn-dimethylaminoethoxy) -a-ethylbemzhydrol is dissolved in 250 ml of acetonitrile and 14 ml of ethyl bromide are added to this solution. The reaction mixture is heated to reflux for two hours, then The cold is left overnight. The next day the solution is concentrated under reduced pressure. The solid residue recrystallizes with acetone. Thus, 17.4 g of a crystalline quaternary compound having a melting point of 113 ° C. are obtained. Example IV. The preparation of 2- (N-benzo-α-ethylbenzhydrol) -5H-chloro-α-ethylbenzhydrol consists in dissolving 5.2 g of 2-amino-5-chloro-α-ethylbenzhydrol in 100 ml of anhydrous acetone and he took 3.4 g of anhydrous acid sodium carbonate with 2.82 g of benzoyl chloride. After completion of the reaction, the inorganic salt was filtered off and the solvent was distilled off under reduced pressure. The residue after distillation recrystallizes from alcohol. This gives g of product with a melting point of 188-189 ° C. Analysis for CH 2 H 2 Cl NO 3: calculated: C 72.22% H 5.51% Cl 9.69% N 3.83% found: C 72.18 % H 5.68% Cl 9.49% N 3.91% characteristic bands of the IR spectrum at 700, 770, 835, 870, 1300, 1540, 1650, 3250 cm "1 XJV spectrum: X ^ ° XH 218, 277 nm Example 5 The preparation of 4-hydroxy-α-vinylbenzhydrol consists in that to 184 ml of a 3.4 molar solution of vinylmagnesium chloride in tetrahydrofuran at 0 ° C within about 30 minutes 20 g of 4-hydroxybenzophenone are added. in 180 ml of anhydrous ether. The reaction mixture is stirred at 0 ° C. for an additional hour, then left to stand at room temperature overnight. The next day, the reaction mixture is poured into an ice-cooled aqueous ammonium chloride solution. The ether layer is washed with water. water until neutralized, and then dried over anhydrous magnesium sulfate. After distilling off the ether, 22.6 g of the above vinyl compound is obtained, which is crystallized is lysed from a mixture of ethyl acetate and n-hexane. Melting point: 104 ^ 105 ° C. Analysis for C15H1402: calculated: C 79.62% H 6.24% found: C 79.55% H 6.18% characteristic IR spectrum bands at 700, 770, 830, 1640, 3280.3410 cm "1 UV spectrum: 1 J ^ 1,228, 278 nm. In an analogous manner to that described in example II, the following compounds are prepared from appropriately selected starting materials: 2-fluoro-α-vinylbenzhydrol with boiling point 91- 93 ° C 97 720 19 analysis for C ^ HuFO: calculated: C 78.92% H 5.74% F 8.32% found: C 79.04% H 5.81% F 8.18% characteristic IR spectrum band at 705, 765, 770, 122fr, 3460, 3580 cm "1 UV spectrum: X" 2 £ f 263, 269 nm. 2,4-dimethyl-α-vinylbenzhydrol analysis for C17H180: calculated: C 85.67% H7. 61% found: C 85.78% H 7.57% characteristic ddma IR band at 705, 760, 825, 870, 2870, 2930, 3460, 3560 cm -1 UV spectrum: XJ ^ fj1 272, 283 nm. 3-amino-4-chloro-α-vinylbenzhydrol analysis for C15H14ClNO: calculated: C 69.36% H 5.43% Cl 13.65% N 5.39% found: C 69.42% H 5.37% Cl 13.59% N 5.41% characteristic bands of the IR spectrum at 705, 765, 805, 875, 3220, 3325 cm "1 UV spectrum: X ** E * 215, 294 nm. 2,4-dimethoxy-α-vinylbenzhydrol melting point: 52-53 ° C analysis for C1H2O6: calculated: C 75.53% H 6.71% found: C 75.53% H 6.88% characteristic IR spectrum band at 705.765. 820, 860, 1030, 1210, 3560 cm * 1 Wdm UV: X EtOH 278, 283 nm. 2.5H Dimethyl-α-vinylbenzhyde Boiling point: 103-104 ° C / 0.05 Analysis for C17HlgO: calculated C 85.67 % H 7.61% found: C 85.58% H 7.59% characteristic bands of the IR spectrum at 705, 765, 815, 850, 2870, 2930, 3460, 3560 cm'1 spectrum XXV: X EtOH 255 (inflection point ), 262, max. 266, 272, 279 nm. 3-trifluoromethyl-α-vinylbenzhydrol, boiling point: 91-92X70.1 analysis for C CH ^F ^O: calculated: C 69.05% H 4 , 71% F 20.48% found: C 69.12% H 4.69% F 20.52% characteristic pa sm spectra of IR spectra at 705, 760, 810, 1125, 1335, 3450, 3360 cm -1 UV spectrum: X EtOH 255 (inflection point), 260, 266, 272 nm. 2,4-dichloro-α-vinylbenzhydrol, boiling point: 136--13137 ° C / 0.15 analysis for: C9H210O: calculated C 64.53% H4.3% Cl 25.40% found : C 64.61% H 4.28% Cl 25.51% characteristic bands of the IR spectrum at 705, 760, 825, 870, 3460, 3570 cm -1 UV spectrum: X JjJgJ1 257, 261, 267, 283 nm. 3 - iodo-.alpha.-vinylbenzhydrol, boiling point: 129-131 ° C. / 0.08 analysis for C12HUO: calculated: C 53.39% H 3.90% J 37.75% found: C 53.50 % H 3.92% J 37.58% characteristic bands of the IR spectrum at 700, 765, 785, 3460, 3560 cm -1 UV spectrum: X JgJ ™ 254, 260 (point of inflection), 280 (point of inflection) nm. 50 55 60 4-bromo-α-v4nylbenzhydiol boiling: 122-123X70.08 analysis for ClSH18BrO: calculated: C 62-30% H 4.53% Br 27.64% found: C 62.15% H 4.48% Br 27.53% characteristic band of the IR spectrum at 705, 765, 825, 3450, 3560 cm "1 UV spectrum: X g &lt; 254, 260, 266, 277 nm. 2-Chloro anvinylbetizhydrol with a boiling point: 123-125TC / 0.1 analysis for O ^ H ^ ClO: calculated: C 73.62% H 5.35% Cl 14.49% Found: C 73.57% H 5.38% Cl 14.41% characteristic IR spectrum band at 705, 760, 3440, 3570 cm -1 UV spectrum: X µgg1 256, 259, 264 nm. 4-fluoro-α-vinylbenzhydrol boiling point: 106-108 ° C / 0.09 analysis for C15H13FO: calculated: C 78. 92% H 5.74% F 8.32% found: C 78.77% H 5.71% F 8.14% characteristic IR spectrum bands at 705, 760, 835, 3460, 3570 cm- * UV spectrum: X ° C 25 ° C (inflection point) 261, 266, 283 nm. 3,4-Dichloro-α-vinylbenzhydrol, boiling point: 139-141 ° C / 0.1 analysis for C, H, 10 ° C: calculated : C 64.53% H 4.35% Cl 25.40% Found: C 64.37% H 4.31% Cl 25.2 8% characteristic band of the IR spectrum at 705, 775, 825, 885, 3460, 3570 cm- * UV spectrum: Jt "S £ f 261, 267, 275, 284 nm. 4-tert-butyl-α-vinylbenzhydrol boiling point: 122-II24 ° C / 0.03 analysis for CifH20: calculated: C 85.67% H 8.33% Found: C 85, 71% H 8.28% characteristic IR spectrum bands at 705, 765, 40 835, 1365, 1395, 2870, 2960, 3460, 3560 cm "1 UV spectrum: X ^ H 256 (inflection point), 260, 266 (point inflection), 274 (inflection point) nm. 3-chloro-α-dimnylbenzhydrol boiling point: ^ 134- ^ 136 ° C / 0.06 analysis for CuB ^ ClO: calculated: C 73.62% H 5.35 % Cl 14.49% Found: C 73.47% H 5.31% Cl 14.57% characteristic bands of the IR spectrum at 705, 755, 790, 3460, 3570 cm -1 UV spectrum: XJ ^ 1 256, 261, 267, 277 nm. 3,4.5- trimethoxy-α-vinylbenzhydrol, mp: 84-85 ° C, analysis for CH 2 H 2 O 4 calculated: C 71.98% H 6.71% found: C 72.10% H Characteristic band of 6.73% of the IR spectrum at 705, 760, 840, 1135, 1450, 3440 cm-1 UV spectrum: X 2 H 268, 272, 281 (inflection point) nm. 4-chloro-α-dnylbenzhydrol and boiling: 134 ^ 136 ° C / 0.1 analysis for C15H18C10: calculated: C 73.62% H 5.35% Cl 14.49% 65 found: C 73.51% H 5 36% Cl 14.35% temperature 97 720 U Characteristic bands of the IR spectrum at 705, 760, 830, 3460, 3670 cni-1 UV spectrum: * E tOH 256, 261, 267, 278 nm. 4-mitffOHi-vinylbenzhydrol, boiling point: 153- ^ 154TC / 0.1 analysis for CH 2 H 2 NO 3: calculated: C 70.58% H 5.13% N 5.49% found: C 70. 68% H 5.10% N 5.51% characteristic bands of the IR spectrum at 700, 770, 855, 1600, 1350, 1500, 1520, 3550 cm -1 UV spectrum: X JJ ^ 1 276 nm. 4- (Pndwii € »Tyloaminoe) tO (kBy) -a-winyk) ibenzhydrol boiling point: 168-172X1 / 0.05 analysis for CnH2SO2: calculated: C 77.50% H 8.36% N 4.30% Found: C 77.49% H 8.21% N 4.41% characteristic bands of the IR spectrum at 705, 765, 835, 1060, 1250, 2820, 3100, 3500 cm * 1 UV spectrum: X1fxH 229, 276, 283 nm. 4-n-butyl-cH-vinylbenzhydrol, boiling point: 136-138 ° C / 0.1 analysis for CH 2 H 2: calculated: C 85.67% H 8.33% found: C 85.86% H 8 21% characteristic IR spectrum bands at 705, 765, 835, 2860, 2880, 2940, 2970, 3460, 3570 ohm-1 IW spectrum: XJ ^ 12 260, 265 nm. PL

Claims (12)

Claims 1. Process for the preparation of pharmaceutically active, new (substituted benzhydrogen derivatives of general formula I, in which Z represents an ethyl or vinyl group, Bi and R * identical or different, denote hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, trichloromethyl groups, nitro, natryl, hydroxyl, alkoxy groups containing 1-6 carbon atoms, amino, aminoalkyl groups, containing 1-4 carbon atoms, alkylamino groups containing 1 - 6 carbon atoms or optionally nitrified mercaptan groups, Rs, R4 and R6, identical or different, mean hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, cycloalkyl groups containing up to 7 carbon atoms, arylalkyl groups containing 1-4 carbon atoms in the alkyl part, phenyl groups, trihalogen groups, miter, niitrile groups, optionally serrated or etherified groups hydroxyl groups, alkoxy groups containing 1-6 carbon atoms, carboxyl groups or optionally acylated amino groups, aminoalkyl groups containing 1-4 carbon atoms, alkylamino groups containing 1-6 carbon atoms, dialkylamino groups containing 1-6 atoms carbon which, optionally with the addition of an adjacent nitrogen atom, can form a ring of up to 8 members, optionally also containing an oxygen atom or further nitrogen atoms and optionally substituted with an alkyl group of 1-4 carbon atoms, an alkylaminoalkyl group containing 1-4 carbon atoms in each alkyl moiety, a dialkylaminoalkyl group containing 1-4 carbon atoms in each alkyl moiety, which optionally with the inclusion of an adjoining nitrogen atom may form a ring of at most 8 members, possibly also containing oxygen or further nitrogen atoms, a bisque group - a lamino group containing 1-4 carbon atoms in each alkyl part, optionally esterified or etherified mercaptan groups and or optionally etherified hydroxyl groups, wherein when Z is an ethyl group Ri, Rg, R * R4 and Rg are not all simultaneously hydrogen and not all simultaneously methyl groups; if Rlf R2, R a and R4 are hydrogen, then Rg has a different meaning than an amino group in the 2 or 4 position, a dimethylamino group in the 2 or 4 position, a 1-pyrrolidinylmethyl group in the 2 position, bromine atom, methyl group or methoxy at position 4; if Rt, R5 and Rs are hydrogen, then R4 and Rg have a different meaning than 2,4-dimethoxy or 3,4- dimethoxy; if Ri and R2 are hydrogen, then R1, R4 and Rg have a different meaning than the 2,4,5- or 2,4,6-trimethoxy, 4-methoxy-3,15- dimethyl or 2-amino-3,5 group ^ dibromic; and in the case where Z is vinyl, if Ru, R, R, and R 4 are hydrogen, then R s has a different meaning than the 4-methyl or hydrogen group, and their acid addition salts and quaternary ammonium salts thereof. of the new compounds, characterized in that the benzophenone of general formula II, in which the meaning of Rlf R * R, R4 and R5 is the same as in general formula I, is reacted with ethylmagnesium or vinylmagnesium halides, the resulting complex compound The grignard is decomposed and the compound of formula I thus obtained is isolated from the reaction mixture and the product obtained is optionally converted into an acid addition salt or into a quaternary ammonium salt and / or the resulting salt liberates the base. 40 2. The method according to claim The process of claim 1, wherein the reactions are carried out in a solvent. 3. Process for the preparation of pharmaceutically active new α-substituted benzhydrol derivatives of the general formula I, in which Z is an ethyl group, R 1 and R 2, identical or different, represent hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, tri-tarethyl, nitro, nitrile, hydroxyl, alkoxy groups containing 1-6 carbon atoms, amino groups, aminoalkyl groups containing 1-4 carbon atoms, alkylamino, containing 1-6 carbon atoms, or optionally esterified mercaptan groups, Rt, R4 and Rg, identical or different, mean hydrogen atoms, halogen atoms, and straight or branched alkyl groups, 1-6 carbon atoms, cycloalkyl groups up to 7 carbon atoms, arylalkyl groups with 1 60 1-4 carbon atoms in the alkyl part, phenyl groups, tricyclomethyl, nitro, nitrile groups, optionally esterified or ether verified hydroxyl groups alkoxy groups, 1-6 carbon atoms, carboxyl groups or optionally acylated amino groups, aminoalkyl groups containing 1-4 carbon atoms, alkyl amino groups containing 1-6 carbon atoms, dialkylamino groups containing 1-6 carbon atoms which, optionally with the inclusion of an adjacent atom, can form a ring of up to 8 members, possibly also containing an oxygen atom or further nitrogen atoms and optionally substituted with alkyl 1-4 carbon atoms, alkylaminoalkyl group containing 1-4 carbon atoms in each alkyl portion, dialkylaminoalkyl group containing 1-4 carbon atoms in each alkyl portion, which, possibly with the inclusion of the adjacent nitrogen atom, may form the maximum 8-membered ring , optionally also containing oxygen or further nitrogen atoms, dialkylamino group having 1-4 carbon atoms in each alkyl part, optionally esterified or zeitified mono groups rkaptam or optionally etherified hydroxyl groups, whereby if R 1, R 2, R a and R 4 are hydrogen then R 5 has a different meaning than the 4-position methyl or hydrogen, and their acid addition and quaternary salts ammonium salts, characterized in that the benzophemon of general formula II, in which the meaning of R1, R2, R3, R4 and R5 is the same as in general formula I, is reacted with a vinylmagnesium halide, the obtained Grignard complex compound is decomposed and the vinyl group thus obtained is reduced to an ethyl group. 4. The method according to p. The process of claim 3, wherein the reactions are carried out in a solvent. 5. Process for the preparation of pharmaceutically active? -Substituted benzhydrol derivatives of the general formula I, wherein Z represents an ethyl or vinyl group, R1 and R2, which are identical or different, represent hydrogen atoms, straight or branched alkyl groups containing 1- 6 carbon atoms, trihalomethyl, nitro, niitrile, hydroxy, alkoxy groups containing 1-6 carbon atoms, amino groups, aminoalkyl groups containing 1-4 carbon atoms, alkylamino groups containing 1-6 carbon atoms because optionally esterified mercaptane groups, R3, R4 and R5, identical or different, are hydrogen atoms, straight or branched alkyl groups with 1 to 6 carbon atoms, cycloalkyl groups with up to 7 carbon atoms, arylalkyl groups with 1 —4 carbon atoms in the alkyl part of the phenyl group, trihalomethyl, nitro, nitrile groups, optionally esterified or etherified hydroxyl groups, alkoxy groups containing 1-6 carbon atoms , carboxyl groups or optionally acylated amino groups, aminoalkyl groups containing 1-4 carbon atoms, alkylamino groups containing 1-6 carbon atoms, di-alkylamino groups containing 1-6 carbon atoms, which optionally with the addition of an adjacent carbon atom nitrogen can form a maximum of an 8-membered ring, optionally also containing an oxygen atom or further nitrogen atoms and optionally substituted with an alkyl of 1-4 carbon atoms, an alkylaminoalkyl group containing 1-4 carbon atoms in each alkyl part, a dialkyl aminoalkyl group, containing 1-4 carbon atoms in each alkyl part, which, optionally with the inclusion of the adjacent nitrogen atom, can form a 5-membered ring of the most, possibly also containing oxygen or further nitrogen atoms, a dialkylamino group containing 1-4 carbon atoms in each part alkyl group, optionally esterified or etherified mercapto groups and or optionally etherified hydroxyl groups, whereby gd y Z is the ethyl group R19, R2, R3, R4 and R5, not all are hydrogen at the same time and not all simultaneously methyl groups; if Rlf R2, R3 and R4 are hydrogen, then R5 has a different meaning than an amino group in position 2 or 4, dimethylamino group in position 2 or 4, 1-pyrrolidinylmethyl group in position 2, bromine atom, methyl or methoxy at position 4; if R1f, R2 and R3 are hydrogen, then R4 and R5 are different from 2,4-dimethoxy or 3,4-dimethoxy; if R! and R2 represent hydrogen atoms, then R3, R4 and R5 have a different meaning than 2,4,5- or 1,4,6- triethoxy, 4-methoxy-3,5-dimethyl or 2-amino-3, 5- di7 bromine; and in the case where Z is vinyl, if R19, R2, R3 and R4 are hydrogen, then R5 has a different meaning than the 4-methyl group or hydrogen, and their acid addition salts and ammonium quaternary salts thereof. of the new compounds, characterized in that the benzophenone of general formula II, in which the meaning of R19, R2, R3, R4 and R5 is the same as in general formula I, is reacted with ethylmagnesium or vinylmagnesium halides, the resulting complex compound The grignard is decomposed and the compound of formula I obtained in this way is dehalogenised. 6. The method according to p. 5. The process of claim 5, wherein the reactions are carried out in a solvent. 7. Process for the preparation of pharmaceutically active, new α-substituted benzhydrol derivatives of general formula I, wherein Z represents an ethyl or vinyl group, Rx and R2, identical or different, represent hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, ttrichloromethyl groups, nitirium, hydroxyl, alkoxy groups containing 1-6 carbon atoms, amino groups, aminoalkyl groups containing 1-4 carbon atoms, alkylamino groups containing 1-6 carbon atoms or optionally esterified mercapitane groups, R3, R4 and R5, identical or different, mean hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, cycloalkyl groups containing up to 7 atoms carbon, aralkyl groups, containing 1-4 carbon atoms in the alkyl part, phenyl groups, trihalomethyl groups, nitro groups, optionally unesterified or etherified hydroxyl groups, alkoxy groups containing 1-6 carbon atoms, carboxyl groups or, optionally, acylated amino, aminoalkyl groups, 1-4 carbon atoms, alkyl amino groups, 1-6 carbon atoms, 97,720 25,26 dialkylamino groups, 1-4 6 carbon atoms which, if appropriate, including the adjacent nitrogen atom, can form a ring of up to 8 members, optionally also containing an oxygen atom or further nitrogen atoms and an optionally substituted alkyl of 1-4 carbon atoms, an alkylaminoalkyl group containing 1 -4 carbon atoms on each alkyl part, a di-dual-amiinoalkyl group, containing 1-4 carbon atoms in each alkyl part, which, optionally with the inclusion of the adjacent nitrogen atom, may form at most a 3-membered ring, possibly also containing oxygen or other nitrogen atoms, dialkylamino group containing 1-4 carbon atoms in each alkyl part, optionally esterified or etherified mercaptan groups, or optionally completely etherified hydroxyl groups, and when Z is the ethyl group R 1, R 2, R 3, R 4 and R 5 are not all hydrogen and not all simultaneously methyl groups; if Ri, R2, R3 and R4 are hydrogen, then R5 has a different meaning than an amino group in the 2 or 4 position, a dimethylamino group in the 2 or 4 position, a 1-pyrrolidinylmethyl group in the 2 position, a bromine group, a methyl or methoxy group in item 4; if R1, R2 and R8 are hydrogen, then R4 and R5 are different from 2,4-dimethoxy or 3,4-dimethoxy; if Rt and R2 are hydrogen, then R8, R4 and R5 have a different meaning than 2,4,5-and relatively 2,4,6-triethoxy, 4-methoxy-3,5-id-dimethyl or 2-amino- 3.5H, two words; and in the case that Z represents a vinyl group, if JR19, R * R3 and R4 are hydrogen, then R3 has a different meaning than the 4-methyl or hydrogen group, and their acid addition salts and quaternary ammonium salts, characterized by where the benzophenone of general formula II, in which the meaning of R1, R2, R8, R4 and R5 is the same as in general formula I, is reacted with ethylmagnesium or vinylmagnesium halides, the obtained Grignard complex compound is decomposed the thus obtained compound of general formula I is hydrolyzed by converting nitrile groups into carboxyl groups. 8. The method according to p. The process of claim 7, wherein the reaction is carried out in a solvent. 9. Process for the preparation of pharmaceutically active new α-listed benzhydrol derivatives of the general formula I, in which Z is an alabolic ethyl group, R 1 and R 2, identical or different, are hydrogen, halogen, millet or branched alkyl groups containing 1-6 carbon atoms, trichloromethyl groups, nitro, nitrile, hydroxyl, alkoxy groups containing 1-6 carbon atoms, aminoalkyl groups containing 1-4 carbon atoms, alkylamino groups containing 1-6 6 carbon atoms or optionally esterified mercaptane groups, R8, R4 and R5, identical or different, mean hydrogen atoms, halogen atoms, straight or branched alkyl groups with 1 to 6 carbon atoms, cycloallkylofv groups up to 7 atoms carbon, aralkydrol, containing 1-4 hydrocarbon atoms in the alkyl part, phenyl groups, trihalogen groups, nitro, nitrile, optionally esterified or etherified 5 hydroxyl groups, alkoxy groups containing 1-6 carbon atoms, carboxyl groups or acylated amino groups, aminoalkyl groups, 1-4 carbon atoms, alkyl amino groups, 1-6 carbon atoms, di-10 alkylamino groups, 1-4 6 carbon atoms which, optionally with the addition of an adjacent nitrogen atom, can form a ring of up to 8 members, optionally also containing an oxygen atom or further nitrogen atoms, and optionally substituted with an alkyl of 1-4 carbon atoms, an alkylaminoalkyl group containing 1-4 atoms carbon on each alkyl moiety, a dialkylaminoalMl group containing 1-4 carbon atoms in each alkyl moiety, which, if appropriate with the inclusion of the adjacent nitrogen atom, may form a maximum 3-membered ring, possibly also containing oxygen or further nitrogen atoms, dialkylamimic acid containing 1-4 carbon atoms in each alkyl part, optionally esterified or etherified mercaptan groups or optionally etherified hydroxyl groups, where when Z is an ethyl group, R 1, R 2, R 8, R 4 and R 5 are all hydrogen and not all simultaneously methyl groups; if Rx, R2, R8 and R4 are hydrogen, then R5 has a different meaning than the amino group in position 2 or 4, dimethylamino group in position 2 or 4, 1-pyrrolidinylmethyl group in position 2, bromine atom, Methyl or methoxy at position 4; if Rx, R2 and R3 are hydrogen, then R4 and R5 are different from 2,4-dimethoxy, or 3,4-dimethoxy; if R ± and R2 are hydrogen, then R8, R4 and R5 have different meanings than the 2,4,5- or 2,4,6-trimethoxy, 4-methoxy-3,5-dimethyl or 2- amlin-3,5-idbromic; and in the case where Z is vinyl, if R 1, R 2, R 8 and R 4 are hydrogen, then R 5 has a different meaning than the 4-methyl or hydrogen group and their acid addition salts and quaternary ammonium salts, characterized by in that the benzophenone of general formula II, in which the meaning of R1, R2, R8, R4 and R5 is the same as in general formula I, is reacted with ethylmagnesium or vinylmaginesium halides, the complex compound obtained is The grignard is degraded and the amino groups are acylated in the thus obtained compound of general formula I. 55 10. The method according to p. The process of claim 7, wherein the reactions are carried out in a solvent. 11. Process for the preparation of pharmaceutically active, cup substituted benzhydrol derivatives of the general formula I, in which Z is ethyl or vinyl, RA and R2, which are identical or different, represent hydrogen atoms, halogen atoms, straight or branched groups alkyl groups containing 1-6 carbon atoms, trichloromethyl groups, nitro, hydroxyl, alkoxy groups containing 1-6 carbon atoms, amine groups, aminoaltooyl groups, containing 1-4 carbon atoms, alkylamino groups containing 1 - 6 carbon atoms or optionally esterified merteaptaine groups, R8, R4 and R5, identical or different, mean hydrogen atoms, halogen atoms, straight or branched alkyl groups containing 1-6 carbon atoms, cycloalkyl groups containing up to 7 carbon atoms, arylbalkyl groups with 1-4 carbon atoms in the alkyl part, phenyl groups, trihalomethyl groups, nitro groups, optionally esterified or etherified hydroxyl groups, alkoxy groups, 1-6 carbon atoms, carboxyl groups or optionally acylated amino groups, aminoalkyl groups with 1-4 carbon atoms, alkylamino groups with 1-6 carbon atoms, dialkylamino groups with 1-6 carbon atoms, possibly with the addition of the adjacent nitrogen atom may form a maximum 8-membered ring, optionally containing either an oxygen atom or further nitrogen atoms and optionally substituted with an alkyl of 1-4 carbon atoms, an alkylaminoalkyl group containing 1-4 carbon atoms in each alkyl part , a di-alkylaminoalkyl group containing 1-4 carbon atoms in each alkyl part, which, possibly with the inclusion of the adjacent nitrogen atom, can form a maximum 3-membered ring, possibly also containing oxygen or further nitrogen atoms, a dialkylamino group, containing 1 -4 carbon atoms in each alkyl part, optionally esterified or etherified 720 28 mercaptain groups or optionally etherified e hydroxyl groups, where when Z is an ethyl group Ru R2, Rs R4 and R5 not all simultaneously represent hydrogen atoms and not all simultaneously methyl groups, if R and R, R2, R8 and R4 represent hydrogen atoms, then R5 has other the amino group in the 2- or 4-position, the dimethylamino group in the 2- or 4-position, the 1-pyrrolidinylmethyl group in the 2-position, the bromine atom, the methyl or methoxy group in the 4-position; if R 1, R 2 and R a are hydrogen, then R 4 and R 5 are different from 2,4-dimethoxy or 3,4-dimethoxy; if Ri and R2 are hydrogen, then R8, R4 and R5 have a different meaning than 2,4,5-or 2,4,6-tri-methoxy, 4-methoxyH3,5-dimethyl or 2 Hamino-3,5-dibromic ; and where Z is vinyl, if Rj, R2, R3 and R4 are hydrogen, then R5 has a different meaning than the 4-methyl group or hydrogen, and their acid addition salts and quaternary ammonium salts, characterized by where the benzophenone of general formula II, in which the meaning of R1 R2, Rs R4 and R5 is the same as in general formula I, is reacted with ethylmagnesium or vinylmagnesium halides, the obtained Grignard complex compound is decomposed in the thus obtained compound of general formula 1, nitrile groups are reduced to aminoalkyl groups. 12. The method according to p. 11, characterized in that the reactions are carried out in a solvent. 97 720 R5 Ri R \ Z ROH Formula 1 R2 or R5 Formula 2