SU1299500A3 - Method for producing derivatives of 1-aryl-2-aminoethanol-1 - Google Patents

Abstract

The invention relates to amino alcohol derivatives, in particular 1-aryl-2-aminoethanol-1 (AE) of the general formula (I): X-Ar-CR (OH), jR, where Ar is phenyl or naphthyl, benzo-1,3- dioxane, thienyl; X - And, C1, Br, lower alkyl, alkoxyl, NOj; K - lower alkyl, H; K and RJ - H, lower alkyl, phenyl, phenylethyl, which are used for the synthesis of biologically active compounds. The purpose of the invention is the creation of a universal method, providing a wider range of compounds of the specified class. The synthesis of AE includes the steps of: a) reacting a sulfide of the general formula (II): R-SCHj, where is n-alkyl, with dimethyl sulfate in a water-immiscible organic solvent (); b) adding to the reaction mixture first an alkali in the presence of a catalyst, tetrabutylammo bromide, and then a carbonyl compound of formula (III): X - Ar - CR, (0), where X, Ar, R, are indicated above; c) removing water and / or part of an organic solvent and treating the residue with an amine of the general formula (IV):, where F, and F are as above. The method provides AE in the form of hydrochloride with a yield of 60-75%. with (oh w x with sp about o see

Description

112995002

The invention relates to a new sop. 191-192 s, the structure of which was confirmed by the PMR method.

PRI me R 3. In the implementation of methods similar to those considered

p 5 of example 1, when 2,2-dimethyl-6-formyl-benzo-1,3-diox-jCaHa is added to the reaction, 2,2-dimethyl-6- (2-tert-butylaminoethan-1) benzo is isolated -1, 3-dioxane in the form of oxalate with a yield of 60%: so pl.

phenyl, naphthyl, benzo-1.3-di-, about 91-92 ° C. whose structure has been confirmed thienyl; method PMR.

hydrogen, chlorine atom or boro- and pyramid 4. When exercising

I am preparing for 1-aryl-2-aminoethanol-1 derivatives of the formula

X-Ar-C-CH -NC

.HE

R

where Ar X R, MA, lower alkyl, alkoxy,

nitro group;

lower alkyl, hydrogen;

procedures similar to that used in Example 1, using p-nitrobenealdehyde when conducting the 5th reaction, isolated 1- (4-nitrophenyl) -2-tertbutylaminoethanol-1 in the form of a base in 75% yield; m.p. 145-147 ° C, the structure of the compound is confirmed by IMP data.

R and R, is hydrogen, lower alkyl, phenyl, phenylethyl.

The aim of the invention is to increase the versatility of the method, i.e., the development of a general method for producing pro-2o derived 2-amino-ethanol, in which the substituent R can be hydrogen or lower alkyl.

Example 1. 8 g (0.05 mol) of methyl octyl sulfide and 7 g (0.055 mol) of 25 dimethyl sulfate are mixed in 25 cm of methylene chloride and left at room temperature for 48 hours. To the resulting solution of dimethyl octyl sulfonium, add 0.15 g of tetrabutylammonium bromide and 25 cm of a 50% aqueous solution of sodium hydroxide, and then with continuous stirring, 9.8 g (0.05 mol) are added dropwise

procedures similar to that used in Example 1, using p-nitrobenealdehyde when conducting the 5th reaction, isolated 1- (4-nitrophenyl) -2-tertbutylaminoethanol-1 in the form of a base in 75% yield; m.p. 145-147 ° C, the structure of the compound is confirmed by IMP data.

PRI me R 5. When carrying out the procedure similar to that used in Example 1, using 1-naphthaldehyde in the reaction, 1- (1-naphthyl) -2-tert-butylamino-ethanol-1 in the form of a base is obtained with the yield 60%; m.p. 125-126 C. The structure of the obtained compound was confirmed by PMR spectrum.

thirty

For example, In a suspension of 16.4 g of crushed sodium hydroxide and 2.5 g of potassium carbonate in 50 cm of methylene chloride, a solution of 3,4,5-trimethoxybenzaldehyde in 25 cm, is added dropwise with mist stirring. 32.5 g (0.11 mol) of methylene chloride methyl sulfate. The reaction mixture of methyloctylsulfonium obtained in the mixture is heated to boiling for 4 hours, after which the organic layer is separated, from which the solvent is distilled off, and 50 cm of isopropanol and 18 g of Q (0.25 mol) of tertbutylamine are added. The mixture is heated to boiling for 8 hours, after which the excess tertbutylamine and solvent are removed by distillation. From the precipitate, 1- (3,4,5-trimetok-, j is obtained. After cooling, the mixture is diluted with syphenyl) -2-tertbutylaminoethanol-1 in 50 cm of methylene chloride and filtered in accordance with Example 1, 22.0 g (0.1 mol) 3,5-dichloro-4-nitrobenzaldehyde and 0.33 g of tetrabutylammonium bromide in 50 ml of methylene chloride at such a rate that the temperature of the reaction mixture does not exceed 25 C. Then the reaction mixture is heated to boiling point for 2 hours.

hydrochloride, its release with a yield of 70% after crystallization from ethanol, and the compound has. mp. 203-205 ° C. The structure of 1- (3,4,5-Grifenoxyethyl-2-tertbutylaminoethanol-1) is confirmed by the proton magnetic resonance spectrum (PMR).

Example 2. Operating according to the procedure similar to that used in Example 1, and therefore using acetophenone, 1-phenyl-1-metsh-2-tertbutylaminoethanol-1 is obtained in 65% yield in the form of hydrochloride, having

procedures similar to those used in Example 1, using p-nitrobenealdehyde when performing the reaction, isolated 1- (4-nitrophenyl) -2-tertbutylaminoethanol-1 in the form of a base in 75% yield; m.p. 145-147 ° C, the structure of the compound is confirmed by IMP data.

PRI me R 5. When carrying out the procedure similar to that used in Example 1, using 1-naphthaldehyde in the reaction, 1- (1-naphthyl) -2-tert-butylamino-ethanol-1 in the form of a base is obtained with the yield 60%; m.p. 125-126 C. The structure of the obtained compound was confirmed by PMR spectrum.

For example, In a suspension of 16.4 g of crushed sodium hydroxide and 2.5 g of potassium carbonate in 50 cm of methylene chloride, a solution of 32.5 g (0.11 mol) of dimethyl octylsulfonyl methylsulfate prepared in Cooling mixture, obtained in Cooling, was diluted 50 cm of methylene chloride and filter in accordance with Example 1, 22.0 g (0.1 mol) of 3,5-dichloro-4-nitrobenzaldehyde and 0.33 g of tetrabutylammonium bromide in 50 ml of methylene chloride at a rate such that the reaction mixture does not exceed 25 C. Then the reaction mixture is heated to penalty for 2 hours.

yut. The solution is washed with 2x50 cm of water and, after drying it with anhydrous magnesium sulfate, methylene chloride is distilled off. The rest is dissolved in 110 cm of isopropanol, 20 cm (0.40 mol) of tert-butyl amine is added and the entire contents are heated to boiling point for 6 hours. Isopropanol and unreacted tert-butyl amine are distilled off under reduced pressure. The thermal brown crystalline residue remaining after this is dissolved in 200 ml of ethanol and 25 cm of Na212 is added.

saturated ethanolic solution of hydrogen chloride. After 10 minutes, ethanol was distilled off and 100 cm of benzene was added to the remaining substances, after which the entire content was cooled to 0 ° C; The resulting creamy crystalline residue is filtered and washed with benzene. 21 g of 1- (3,5-dichloro-4-nitrophenyl) 2-tertbutylamino-ethanol-2-hydrochloride are obtained with a yield of 61.4% | T. square 250-255 ° C (decomposition), the structure was confirmed by PMR-studies of the base.

Example 7. When implementing a procedure similar to that used in Example 6, adding 2-nitrobenzaldehyde to the reaction yields 1- (2-nitrophenyl) -2-phenylamino-ethanol in the form of the hydrochloride in 65% yield. Elemental results

By proceeding as in Example 8 and entering into the interaction 2-nitrobenzyl-aldehyde and aniline, 1- (2-nitrophenyl) -2-phenyl-aminoethanol-1 is obtained,

analysis:

I

Calculated,%: C 57.10) H 5.1; N 9.53,

Found,%: C 56.90; H 5.20; N 9.46,

The structure of the compound was confirmed 25 which is reduced by iron by PMR.

PRI me R 8. 1- (2-thienyl) -2-di-isopropyl-aminoethanol-1.

in hydrochloric acid, 42% of 1- (2-aminophenyl) -.- phenylamino-ethanol-1 is obtained with m, m.

19 cm methyl octyl sulfide, 10.6 cm C.

dimethyl sulfate and 50 cm of methylene chloride are mixed and incubated at room temperature for 24 hours. Then, the resulting solution of sulphonic acid salt is loaded into a round bottom flask equipped with a stirrer, reflux condenser and a dropper, and 50 cm of a 50% aqueous solution is added

sodium hydroxide. To received such

the two-layer system add

drop by drop solution containing 9, 2 cm Q

2-thien-acetaldehyde, 0.8 g of tetrabutylammonium bromide and 50 cm of chloride

methylene. After dropping the system

stirred at 42 ° C for 5 h.

After cooling, the layers are separated from the--amine and heated to boiling for Example 12. 23.8 g of methyldodecylsulfide, 13.9 g of dimethyl sulfate and 50 ml of benzene are heated for 3 hours at 80 ° C. Then cooled to 20 ° C and 13.6 g of methoxybenzoic aldehyde, 0.6 g of tetrabutylammonium bromide and 30 ml are added 50% aqueous solution of sodium hydroxide. The whole mass is vigorously stirred at 20 ° C under a protective atmosphere of nitrogen for 12 hours. Then the layers are separated and the benzene is evaporated. The remaining portion is dissolved in 50 ml of ethanol, and 120 ml of a 30% ethanolic solution of methylgon is added to methylene chloride. The remaining portion is dissolved in 50 cm of isopropanol, 11.8 cm of diisopropylamine are added and the mixture is heated to boiling for 8 hours. Then, isopropanol and unreacted agated amine are distilled off under reduced pressure, and methyl octyl sulfate is distilled off with steam. The residual oil is purified by chromatography. Get 1- (2-jie-j Nile) -2-diisopropylaminoethanol-1 in the form of a colorless oil with a yield of 42%. The structure of the compound was identified by a spectroscopic method (H).

6 hours. Ethanol and unreacted amine are evaporated and the remaining part is distilled off under reduced pressure. 22.0 g of methyl dodecyl sulfide (m.p. 122 C / 0.8 torr) and 12.3 g of 1- (4-methoxyphenyl) -2-methyl-aminomethanol (m.p. 150 C / 0 , 8 torr) m. Pl. 103-104 ° C.

The proposed method is universal (common), since it allows to obtain a wide range of 2-aminoethanol-1 derivatives, which could not be obtained by a known method.

PRI me R 9. 1- (3-bromophenyl) -2-to- (o (.-Phenylethyl) amino 3-ethanol-1

Proceed as in Example 8 and using 3-bromobenzylaldehyde, iOC-phenyl-ethylamine as starting compounds, 1- (3-bromophenyl- (() -phenylethyl) -aminZ-ethanol-1 is obtained in the form of a hydrochloride with a mp of 203-205 ° C. The yield is 72%.

Example 10. 1-phenyl-1-propyl-2- (H-morpholine) -thanol-1.

Proceed as in Example 8 and carrying out the reaction of butyrophenone and morpholine, with a yield of 64%, 1-phenyl-1-propyl-2- (M-morpholine) -ethanol is obtained with a yield of 64%. 220-223 C (decomposition).

Example 11. 1- (2-aminophenyl) -2-phenyl-aminoethanol-1.

By proceeding as in Example 8 and entering into the interaction 2-nitrobenzyl-aldehyde and aniline, 1- (2-nitrophenyl) -2-phenyl-aminoethanol-1 is obtained,

 reduced by iron

in hydrochloric acid, 42% of 1- (2-aminophenyl) -.- phenylamino-ethanol-1 is obtained with m, m.

Example12. 23.8 g of methyldodecylsulfide, 13.9 g of dimethyl sulfate and 50 ml of benzene are heated for 3 hours at 80 ° C. Then cooled to 20 ° C and 13.6 g of methoxybenzoic aldehyde, 0.6 g of tetrabutylammonium bromide and 30 ml are added 50% aqueous solution of sodium hydroxide. The whole mass is vigorously stirred at 20 ° C under a protective atmosphere of nitrogen for 12 hours. Then the layers are separated and the benzene is evaporated. The remaining portion is dissolved in 50 ml of ethanol, 120 ml of a 30% ethanolic solution of methylamine are added and heated to boiling for 6 hours. Ethanol and unreacted amine are evaporated and the remaining part is distilled off under reduced pressure. 22.0 g of methyl dodecyl sulfide (m.p. 122 C / 0.8 torr) and 12.3 g of 1- (4-methoxyphenyl) -2-methyl-aminomethanol (m.p. 150 C / 0 , 8 torr), so pl. 103-104 ° C.

The proposed method is universal (common), since it allows to obtain a wide range of 2-aminoethanol-1 derivatives, which could not be obtained by a known method.

F o rmula of the invention

The method of obtaining derivatives of 1-aryl-2-aminoethanol-1 of the formula

 / К Х-АГ-С-Ш2- КС

HE

n

where Ag is phenyl, naphthyl, benzot1,3 dioxane, thienyl; X is hydrogen, chlorine atom or

bromine, lower alkyl, alkoxy, nitro; R) is lower alkyl, hydrogen Rj and RJ are hydrogen, lower alkyl, phenyl, phenylethyl,

including treatment of the carbonyl compound with an amine, isolation and purification of the target product, characterized in that, in order to enhance the editor S.

Compiled by L.Ioffe L. Tehred L. Serdyukov Proofreader E. Roshko Order 905/63 Circulation 372 Subscription

VNIIPI USSR State Committee

for inventions and discoveries 113035, Moscow, Zh-35 Raushsk nab. 4/5

Production and printing company, Uzhgorod, st. Project, 4

g

0

This method is universal, the sulfide of the general formula RSCH ,,

where R is primary, is alkyl,. is reacted with dimethyl sulfate in the medium of an organic non-water-miscible solvent, the reaction mixture obtained in the presence of a catalyst, tetrabutylammonium bromide, is reacted with an alkali metal hydrate and then with a carbonyl compound of the general formula

" one

where R and X are the indicated values, after which water and / or part of the organic solvent are removed and the remaining mixture is treated with an amine of the general formula

R —NH-R ,,,. where R and Rg have the indicated meanings.

Claims (1)

Claim The method of obtaining derivatives of 1aryl-2-aminoethanol-1 of the formula X-AT-S-CH ^ X w where Ar is phenyl, naphthyl, benzo-1,3 dioxane, thienyl; X is hydrogen, a chlorine or bromine atom, lower alkyl, alkoxyl, nitro group; R ₍ is lower alkyl, hydrogen; R ₂ and Rj are hydrogen, lower alkyl, phenyl, phenylethyl, including treatment of the carbonyl 20 compound with an amine, isolation and purification of the target product, characterized in that, in order to increase the universality of the method, sulfide of the general formula RSCH ,, where R is primary C ₄ -C, _r- alkyl,. subjected to interaction with dimethyl sulfate in an organic medium of water-immiscible solvent, the reaction mixture obtained in the presence of a catalyst - tetrabutylammonium bromide is reacted with an alkali metal hydrate, and then with a carbonyl compound of the general formula X-Av-C = 0 where R and X have the indicated meanings, after which water and / or part of the organic solvent are removed and the remaining mixture is treated with an amine of the general formula r ₂ -nh-r ₅ ,. where R ₂ and R ₃ have the indicated meanings.