The method of obtaining e-5-bromopentane-2

 

(57) Abstract:

Usage: as synthons in the synthesis of biologically active compounds, prostaglandins, vitamins, pheromones, juvenile hormones. The inventive two-stage processing of the source cyclopropylethanol: first tribromide phosphorus in an inert absolute solvent in the presence of anhydrous lithium salts and organic bases, for example pyridine, at a temperature of minus 10 - 60oWith, then the selected 1-bromo-1-cyclopropylethyl treated with anhydrous zinc bromide in an inert absolute solvent, for example diethyl ether, tetrahydrofuran, at a temperature of minus 10 - 50oC. Receive 5-bromo-penten-2E (TRANS)-configuration 96%, Regio - and stereochemical purity with a yield not less than 80 %. 4 C. p. F.-ly.

The invention relates to a stereo - and regioselective methods of synthesis of the E(TRANS)-gomoallilnymi bromides synthons of biologically active compounds, prostaglandins, vitamins, pheromones, juvenile hormones, etc. namely, the method of production of E-5-bromopentane-2.

A method of obtaining E-5-bromopentane-2, based on the reaction of disclosure cyclopropanol ring source is th way to obtain E-5 bromantane-2 is low Regio - and stereoselectivity of this reaction, resulting mixture of several compounds. So in reaction to the disclosure cyclopropanol ring source cyclopropylethanol 47% Hydrobromic acid in accordance with the decision of the prototype is formed a mixture of four compounds:

CH3- CH-(CH2)2-Br+

(1)

+CH-(CH2)2Br+CH3- E-5-bromantan-2 (I), Z is 5-bromantan-2 (II) 1-bromo-1-cyclopropylethyl (III) and 1-bromo-2-methylcyclobutane (IV).

Isolation and purification of the target product E-5-bromopentane-2 in this case is extremely difficult and practically does not provide the required purity of the product due to the close physical constants resulting from the reaction of the compounds, while the synthesis of biologically active compounds imposes high requirements as to isomeric and stereochemical purity of the individual components, because even a small admixture (1%) gomoallilnymi bromide Z-configuration does not allow to use it in stereo and regionalplanning the synthesis of natural biologically active substances.

The problem to which the invention is directed, is to develop a Regio - and stereoselective method for the synthesis of E-5-bromo-pentene-2 a high degree of Regio - and stereochemie tasks developed the method of obtaining E-5-bromopentane-2 by processing cyclopropylethanol bromodomain reagent, followed by separation of the reaction products, in which, according to the invention, the first source cyclopropylethanol process tribromide phosphorus in an inert absolute solvent in the presence of anhydrous lithium salts and organic base at a temperature of minus (10-60)aboutWith, followed by separation of the resulting 1-bromo-1-cyclopropylethanol, which is then treated with anhydrous zinc bromide in an inert absolute solvent at a temperature of minus (10-50)aboutC. it is reasonable as an absolute solvent to use ethers, mainly, diethyl ether or tetrahydrofuran.

It is also advisable to use as an organic base pyridine.

By this way we obtain a final product of high degree of Regio - and stereochemical purity, suitable for further synthesis of biologically active compounds.

Similarly can be obtained and E-5-Harpenden-2 when used as halogenous agent in the first stage, phosphorus trichloride and the second anhydrous zinc chloride under the same process conditions as in the case of receiving E-5-bromopentane-2.

The essence of the invention, making the th, in two stages.

In the first stage under the influence of haloesters agent, which is selected trichromacy phosphorus, in the presence of anhydrous lithium salts in an inert absolute solvent (diethyl ether, tetrahydrofuran, and others ) in the presence of organic bases, mainly, pyridine, at a temperature of minus (10-60)aboutWith the substitution occurs hydroxyl group source cyclopropylethanol on bromine

CH3- CH3- (2)

After separation of the resulting 1-bromo-1-cyclopropylamino conventional methods carry out the second stage of actually getting 5-bromopentane-2 E(TRANS) configuration by disclosure cyclopropanol ring under the action of anhydrous zinc bromide in an inert absolute solvent at a temperature of minus (10-50)aboutWITH:

CH3- CH3- -(CH2)2-Br (3)

The use of anhydrous zinc bromide as reagent that will reveal cyclopropanol ring and formation of a double bond, allows you to receive E-5-bromantan-2 a high degree of Regio - and stereochemical purity.

After separation by conventional methods is the end product of E-5-bromantan-2 obtained with the yield of 80% identification methods Pamvotida example implementation of the method.

P R I m e p. E-5-bromopentane-2 is carried out in two stages: "a" and "b".

a) Obtaining 1-bromo-1-cyclopropylamine.

To a mixture of 4.1 g (0.05 mol) of cyclopropylethanol, 3 ml (0,037 mol) in abs. pyridine, 8,3 g (0.09 mol) of anhydrous lithium bromide in 80 ml of abs. diethyl ether at a temperature of minus 30aboutWith added dropwise 3 ml (0.03 mol) trichromate phosphorus.

The reaction mixture is stirred at a temperature of minus 30aboutC for 1 h and poured into ice water.

The organic layer was separated, washed with water, sodium hydrogen carbonate solution, sodium chloride solution, then dried with magnesium sulfate. The ether is distilled off and the residue is distilled in vacuum.

The result: 4.5 g (62%) of 1-bromo-1-cyclopropylamino with the following physico-chemical characteristics: boiling point: 55-58aboutC/75 mm RT. Art. According to the analysis of gas-liquid chromatography (GLC) the purity of the obtained product 97% RangeIH-NMR (CCl4, , M. D.): 0,3-1,3, m, 5H (cyclo3H5-); 1,5, g, 3H, J 6 Hz (CH3-); 3,2, m, 1H, J16 Hz, J28 Hz (-CH(Br)-).

b) Receiving E-5-bromopentane-2 (final product).

To a mixture of 4 g (0.018 mol) of anhydrous zinc bromide in 10 ml of the of Propylamine in 5 ml of abs.the ether. The mixture was stirred at 0aboutWith within days, poured into ice water, the organic layer was separated, washed with water, sodium chloride solution, dried with magnesium sulfate. The ether is distilled off, the residue is distilled in vacuum.

The result obtained 3.7 g (80%) E-5-bromopentane-2, the boiling temperature of 68-70aboutC/100 mm RT. senior purity according to GC is not lower than 96% of RangeIH-NMR (CDCl3, , M. D.): 1,61 m, 3H (CH3CH=) 2,47 m, 2H, (-CH2CH=); 3,30 m, 2H, (CH2Br); 5,34, m, 1H (= ) 5,49, m, 1H (=CH-CH2-); J (SN=SN)of 13.9 Hz.

From the presented data it follows that the resulting product has a high Regio - and stereochemical purity constant spin-spin interaction J is 13.9 Hz, which clearly indicates the TRANS configuration of double bonds.

The applicant did not know the ways to obtain E-5-bromopentane-2, characterized by the set of essential features that are identical to the essential features of the claimed invention.

1. The METHOD of OBTAINING E-5-BROMOPENTANE-2 by processing cyclopropylethanol brainwashin agent, characterized in that as brainwashes agent use trichromacy phosphorus and the process is conducted in an inert absolute solvent in prisutstvie 1-bromo-1-cyclopropylethyl, which is then treated with anhydrous zinc bromide in an inert absolute solvent at a temperature of minus (10 - 50)oC.

2. The method according to p. 1, characterized in that as an absolute solvent used simple aliphatic ether.

3. The method according to PP.1 and 2, characterized in that as the inert solvent used diethyl ether.

4. The method according to PP.1 and 2, characterized in that as the inert solvent used tetrahydrofuran.

5. The method according to PP.1 to 4, characterized in that the organic base is used mainly pyridine.

 

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