SU420178A3 - - Google Patents

Description

(54) METHOD FOR OBTAINING ARYLKETONE DERIVATIVES

oxidizing agents such as manganese dioxide, chromic acid, chromates, oxygen, ozone, dimethyl sulfoxide, potassium permanganate, osmium oxide, and organic peracids. Opnenauer oxidation or photo-oxidation can also be used. The reaction is usually carried out in an aqueous medium or in an organic solvent at a temperature of about -40 ° C; lower or higher temperatures may also be used. The organic solvents used in the oxidation may be petroleum ether, ether, chloroform, carbon tetrachloride, benzene, acetic acid, acetone, pyridine, ethyl acetate, etc.

The resulting final product of general formula I can be converted, if necessary, into an acid addition salt by treating it with a mineral organic acid.

According to the proposed method, the following compounds are synthesized:

7- (4-methyl-1 -piperazinyl) -n-fluorobutyrophenone

y- (4-ethyl-1-piperazinyl) -n - fluorobutyrophenone

7- (4-isop, ropil-1-piperazinyl) - l - fluorobutyrophenone

7- (4-benzyl-1-piperazinyl) - n - fluorobutyrophenone

(| 3-phenethyl) -1-piperazinyl - p - fluorobutyrophenone

(| 3-l-chlorophenethyl) - 1 - piperazinyl - fluorobutyrophenone

(p-l-methylphenethyl) - 1 - piperazinyl l-fluorobutyrophenone

y- (4-phenyl-1-piperazinyl) - l - fluorobutyrophenone

(o-chlorophenyl) - 1 - piperazinyl - lfluorobutyrophenone

(o-bromophenyl) - 1 - piperazinyl - pfluorobutyrophenone

(o-fluorophenyl) -1-piperazinyl-fluorobutyrophenone

(o-iodophenyl) -1-piperazinyl - p-fluorobutyrophenone

(o-methoxyphenyl) - 1 - piperazinyl-lfto. rbutyrophenone

(o-methoxyphenyl) - 1 - piperazinyl-ltrifluoromethylbutyrophenone

(o-methoxyphenyl) - 1 - piperazinyl-zfluorobutyrophenone

(o-methoxyphenyl) -1-piperazinyl-fluorobutyrophenol

PRIdeR 1.

To a floating mixture, 5 g of 1- (l-fluorophenyl) -4- (4-methyl-1-piperazinyl) -1-butanol a and 100 ml of acetone are added dropwise a solution of chromic acid prepared from 2 g of chromic anhydride, 5 ml of water and 2 ml of sulfuric acid, while cooling with ice.

The mixture is stirred overnight at room temperature, poured into 600 ml of cold water and alkalinized with a 10% aqueous solution of caustic soda. The separated basic substance is extracted with 200 ml of chloroform, and the extract is washed with water, dried over anhydrous sodium sulphate and evaporated.

The residual oil is distilled under reduced pressure and the fraction boiling at 116-119 ° C (0.1 mmHg) is collected to give Y- (4methyl-1-piperazinyl) -l-fluorobutyrophenone, the hydrochloride of which melts with decomposition

nri 233-235 ° C.

In accordance with the procedure described above, the following compounds were obtained in high yields:

dihydrochloride (s-chlorophenyl) -1-piperazinyl-propyl- (2-thienyl) ketone, so pl. 204-205 ° C;

4- (t lphenyl) - -piperazinyl-propyl- (2-thienyl) ketone dihydrochloride, t. pl. 215-218 ° C.

Example 2. To a solution of 2.0 g of 1- {l-fluorophenyl-4) -4-benzyl-1-piperazinyl) -1-butanol in 40 ml of benzene was added 10 g of a fine powder of manganese dioxide. The mixture is stirred at room temperature for 10 hours, the precipitate is filtered off and washed with 20 ml of benzene. The combined filtrate and washings are concentrated under reduced pressure. The oily residue is distilled and the fraction boiling at 170-174 ° C (0.1 mmHg) is collected, yielding 7- (4-benzyl-1-piperazinyl) -l-fluorobutyrophenone, which solidifies on standing to crystalline solid, melting at 64-65 ° C. Its hydrochloride melts at 245-247 ° C.

According to the procedure described in Example 2, the compounds listed in Table 2 were obtained. one.

Example 3. To a solution of 2 g of 1-phenyl-4-4 (2-pyridyl) -1-piperazinyl -1-butapolav

60 ml of chloroform are added with 10 g of finely powdered manganese dioxide powder.

The mixture is stirred at room temperature for 8 hours, the precipitate is filtered off and washed with 20 ml of chloroform. The combined filtrate and washings were evaporated to dryness under reduced pressure. The residue is unrecrystallized from a mixture of diisonropyl ether and hexane to give (2-pyridyl) -1-piperazinyl-butyrophenone, melt-idys at 63-65 ° C.

According to the procedure described in Example 3, the compounds listed in Table 2 are obtained. 2

) bCO-CH.z-CHa-CH2- / L- (CHg) X --./

Table 1

- T. pl. hydrochloride

R

; ssn-sn-sn2-sn2-n-a

table 2

The subject of the invention is 1. A method for producing arylketoia derivatives of the general formula

Ar-C-CH2-CH2-N K- (CH) -R O

where Ar is thienyl, phenyl or phenyl substituted by a halogen atom, alkyl with 1-3 carbon atoms, alkoxy with 1-3 carbon atoms, or trifluoromethyl,

Claims (4)

1 - hydrogen atom, alkyl with 1-3 carbon atoms, phenyl or phenyl substituted by halogen atom, alkyl-, alkoxy group with 1-3 carbon atoms, or five or six Ar-CH-CH2-CH2-CH2-} J, (CH, VTl P where Ag, Kit have the indicated values, are oxidized with an oxidizing agent, followed by isolation of the target product by known methods in free form or in the form of a salt. 2. A method according to claim 1, characterized in that manganese dioxide, chromic acid, chromates or potassium permanganate are used as the oxidizing agent. 3. Method according to c. 1, characterized in that the reaction is carried out in water or in an organic solvent. 4. A method according to claim 1, characterized in that the reaction is carried out at a temperature of from 0 to 40 ° C. a member heterocyclic group containing N, O and / or S as a heteroatom, unsubstituted or substituted by alkyl with 1 to 3 carbon atoms, t is O, 1 or 2, or salts thereof, characterized in that the arylbutanol derivative of general formula II Priority signs: 04.11.69 with Ar - phenyl unsubstituted, phenyl, substituted by halogen atom, R is a hydrogen atom, isisyl alkyl, phenyl unsubstituted, qbeyl, substituted by alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms, halogen, 12/09/199 with Ar-phenyl substituted with trifluoromethyl, alkyl- or alkoxyl containing 1-3 carbon atoms, or 2, 12.10.69 at R - an unsubstituted or substituted by alkyl with I-3 carbon atoms of a five- or six-membered heterocycle containing as the heteroatom N, O, and / or S.