SU648081A3 - Method of otaining aminopropanediols - Google Patents

Description

The invention relates to a process for the preparation of new, not described in the literature, aminopropavdiols, which can be used as intermediates in organic synthesis. The patent and technical literature widely describes the addition of amines to olefinic fl compounds, as well as the reduction of carboxylic acid derivatives in alcohol using complex (complex metal hydrides 2j). The aim of the invention is to develop a method for producing new compounds: valuable properties. The goal is achieved by the described method, based on the well-known reactions outlined. A method is described for the preparation of aminoprrhandiols of the general formula B — Jlr —CH — tHlCHsjOH), where R is methyl. nyl benzyl} D is phenyl, oudfechsh, methoxyphosh, methylphenyl, benzyloxyphenyl, or 3-pyridyl, which consists in that diethylbenzalmalonate of the general formula AgCHN-СССОгС Н,) (1 where Ar has the above values, is reacted with dimethyl amine of the formula RRNH (III) where the above values, in the presence of ether at room temperature, followed by reduction of the diethyl (α (.-substituted amino) benzylmalonate of the general formula) thus obtained. (NRR) CH (COiC2H5) 2 where R and Ar have the above values, the complex metal hydride in an organic solvent.

Potency lithium or sodium lithium hydride is used as a co-complex metal hydride.

The organic solvent used is predominantly benzene or tetrahydrofuran.

Example 1. Preparation of diethyl e4shroe benmalmalonic acid.

Dietroxy ester of benalmalic acid. 212 g (2 mol) of benzalvdehyde, 32O g (2, O mol) of malonic acid diethyl ester and 10 ml of piperidine are heated with reverse chlorolyl to 4OO ml of benzene. In the azeotropic distillation with a Dean and Stark trap, the theoretical amount of vediethyl esters of benzalkvlonic acid is selected.

648081

d for 7 hours. After cooling, the reaction mixture is poured into water. The aqueous mixture is extracted with ether and the extract is washed successively. satiated

Sodium hydroxide, water, sodium bicarbonate solution and, finally, water are dissolved in water. The extract is dried over anhydrous magnesium sulphate and ether is isolated until an oil is obtained. This oil is distilled and a fraction boiling at 140 ° C is collected; the output of benzalmalonic acid diethyl ester 343 g, I

In the manner described in this example.

get the diethyl esters of benzalmalonic acid, are given in table. one.

Table 1

(С02СгН5) g

4-SN.O 21O-222 0.10)

Example 2. Preparation of diethyl ester of (eI-substituted-amino) -benzylmalonic acid.

Diethyl 8-fat Co-Substituted. Themselves but) be kzylmalonic acid. 10 O g (2.2 mol) of anhydrous dimethylamine is dissolved in 20 O ml of ether and the solution

cooled to OS in an ice bath. To the cooled solution, 2OO g (O, 81 mol) of diethylmalonic acid diethyl ester in ether are quickly added with stirring. The mixture is stirred at room temperature for 12 hours, and then evaporated in Vacuum and ncwyw 24O g of (5c-dimethylamino) -benzylmalonic acid diethyl ester. In general, these esters do not purify by reapplication of instability. They are characterized by a spectrum of nuclear magnetic resonance. In the manner described in Example 2, the following intermediates are obtained; diethyl (c6-dibutsh1amine) -bea zilmalonic acid; diethyl ether {cC-Diethylamine) -beviz malonic acid; diethyl ether (o6-dimethylamine) - (2-methyl-benzyl) - "malonic acid; diethyl ether (oC-Shmetsh1amin) - (2-chlorobenzyl) -malonic acid; diethyl ether (oC-dimesh1amin) - {4-chlorobenzyl) -malonic acid; diethyl ether (o6-dimethylamine) -, 4-dichlorobenzyl) -lenoic acid; diethyl ether (clCdimethylamine) -3-methoxybenzyl) -alonic acid; (ot-di-methylamine) - {4-methoxybenzyl) -malonic acid diethyl ester; {o6-dimethylamine) - (3-β-bivyloxybenzyl) -malonic acid diethyl ester; diethyl ether (o6-dimethylamine) - (4-benzyloxybenzene 1) -malonic acid; diethyl ether (oC-di methylamine M 3-hydroxybenzyl) -malonic acid; diethyl ether (SzS-Dim8thylamine) -. {4 “P. -oxibenzyl) -malonic acid; diethyl ether (cC-Dimethylamine) - (4-acetoxybenzyl) -malonic acid;

 V. i:, H-CH ((iH20H) g

2-CH Oil

3-CH. 100 69.92 9.48 6.27 69.79 9.26 6, O4

92

65,258,855,8565,268,815,59

102 65,258,855,8565,469, O95.69

Butter

90 59,137,445,7559,347,745,97

120 59,137,445,7559,147,206.03

1,3-P {yupandvola diethyl ether 1cC-dimethylamine) - (4-j-fluorobenzyl) -malonic acid. Example 3, Preparation of 2 (o6-substituted amine} -benyl-1,3-propanediols, Bis- (2-methoxyethoxy) -aluminum sodium {45O ml, 1.6 mol) as a 7O% solution in benzene is dissolved in 2 ml of anhydrous benzene and the solution is cooled in an ice bath. Diethyl ether (o6-dimethylamino) benzylmalonic acid (240 g, 0, O1 mol) is added dropwise to the cooled reaction mixture with stirring. The mixture is stirred for approximately 12 hours at a temperature that rises spontaneously to room temperature. Then the reaction mixture is shifted with an ice cream and a dilute sodium hydroxide solution and extracted twice with ether. The ether extract is washed with water and evaporated in vacuo. The residual maolo is dissolved in 500 ml of petroleum ether, the solution is concentrated by mixing on a steam bath, and petroleum ether is added until turbid. The mixture is then cooled to start. crystallization and get 85 g of 2- (cC-dimethylamino) -benzyl- J., 3- "ropanediol with T.PL. TE-boa In the manner described in Example 3, the following 1,3-propanediols are obtained, which are listed in the following table. 2. T a l and c a 2.

1,3-propanediols

f

CH-CH (lH20H) j

at

4-F

85

72.12 8.28 4.43 72.38 8.45 4.36 Pr i m 4 p, Preparation of 2- {c6-dimethyne amine) (2 - mechSch1beneyl) 1, 3-perch. Diethyl ether (4-metalbenz b) - 4-alkalvoy acid. Saosobom, described in Example 1, carried out the interaction of tolyl aldehyde (SO, g, O, 83 mol) with diethyl malonate | 133 g, O, 83 mol) and piperidine (5 ml) in benzene. The yield of dimethyl ether (4-metsh1benzal) -malonic acid is equal to 89 g, t. Kip. (O, 7 mm Hg. Found,%: C 68.94; H 7, Ov. Calculated,%: C 68.68; H 6.92. Diethyl ether (cCm and methyl n) - (4-methylbenzyl) - malonic acid. Analogously to example 2, diethyl ether {4-methslbenzal) -malonic acid (20 g) is reacted with anhydrous dimethylamine {100 ml) in ether to obtain 22 g of dazthyl ether (oC-dimethylamine) - (4-methylbeneyl) malonic acid oil. , 2- (X.-Dimethylamine) - (4-meth: "1sh) ben, 3-propandiol. Diethyl ester with irtlHMeTia: aMHH) - (4. -Methylbenzyl) -malonic acid (22 g of 6.77 mol) in 10 O ml of benzene dobaap tpT dropwise to a solution of sodium bis- (2-methoxyethoxy) -alumone sodium (28 ml, O, 2 mol) in vvd 7 O% solution in be-azole. (In 10 O ml of benzene), cooled in an ice bath .. After spontaneous heating of another room temperature, the reaction mixture is heated under reflux for an hour. Then the cooled reaction mixture is decomposed with a dilute sodium shdrrrkisi solution. After the Radel and the phases, the benzene layer is washed with water, extracted with dilute hydrochloric acid and washed with water. From this basics get 6 g of neutral oil. Acidic water} extract alkalinized ammonium hydroquin and extract the ether. The ethereal extract is washed with water, dried over anhydrous magnesium niobate, and mixed up dry. The solid, the residue is recrystallized from a mixture of afilace yta and hexane, and 2.7 g of 2- (oC-dimesh1amin) -4-methyl benzyl), 3N ropa diol are obtained; m.p. “P Found,%: C 70.08} And 9.55: 6.05. WITH . Calculated,%: C 69.92; H 9.48; 6.27. Example 5. Preparation of 2- (o, n1methylamine) - (3-pryshshl) -. Metsh1-1, 3-propane diol. Diethyl ether (3-pyridyl) methylene malonic acid. 100 g (0.935 mol) of 3-pyrvdin-carboxaldehyde, 150g (O, 935 mol) of malt novol acid and 5 ml of piperidine are heated under reflux for 16 hours in 20O ml of benzene and distilling with 17 ml of water for 16 h. The cooled reaction mixture is introduced into water and the benzene phase is separated. This phase is then washed down successively with a dried sodium bicarbonate solution and water, dried over anhydrous water.