Method for producing 1,2-bis(2-aminoethoxy)benzene

 

(57) Abstract:

The invention relates to the production of intermediates for macroheterocyclic compounds visa and sacroiliac. The way passes through a three-stage scheme, including: 1) receiving-2-chloroethylamide of N-acetylethanolamine and chloride tiomila when heated in the environment, benzene, toluene or chloroform; 2) alkylation of pyrocatechin N-2-chloroethylamide when the molar ratio of reactants is 1: 2 in n-butyl alcohol in the presence of sodium hydroxide and a catalytic amount of energy balances; 3) the hydrolysis of 1,2-bis (N-2-acetylbenzoate)-benzene aqueous solution of sodium hydroxide under heating, followed by extraction with n-butyl alcohol, 1,2-bis(2-aminoethoxy)benzene and distillation of the solvent. The proposed method can simplify the process by using commercial available reagents, as well as to increase the yield of the target product. table 1.

The invention relates to an improved process for the preparation of 1,2-bis(2-aminoethoxy)benzene, which finds application in the synthesis of Aza - and discrimnation.

The known method for producing 1,2-bis(2-aminoethoxy)benzene in two ways [1] . According to the first ditosylate 1,2-bis(2-guide the Ute hydrazine hydrate in ethanol. The second option ditosylate 1,2-bis(2-hydroxyethoxy)benzene miniroot sodium azide for 24 hours. Then designee derived restore with lithium aluminum hydride in ether for 24 hours prior to 1,2-bis(2-aminoethoxy)benzene.

The full scheme of the synthesis according to the method should also include the stage of producing 1,2-bis(2-hydroxyethoxy)benzene and its ditosylate, as they are not industrial, and, therefore, it should consist of four stages.

The disadvantages of this method is the use of scarce they are flammable and explosive, toxic chemicals: hydrazine hydrate, sodium azide, lithium aluminum hydride, ether, and significant duration of individual stages.

The essence of the proposed method is to simplify the process technology, the use of commercial available reagents, the increase in the yield of 1,2-bis(2-aminoethoxy)benzene, which is achieved by obtaining 1,2-bis(2-aminoethoxy)benzene by alkylation of pyrocatechin in butanol N-2-chloroethylamide with subsequent hydrolysis of 1,2-bis(2-acetylbenzoate)benzene solution of sodium hydroxide. Required for stage alkylation of N-2-chlorotoluene obtained from N-acetylethanolamine the action of chloride It is that obtain 1,2-bis(2-aminoethoxy)benzene is carried out with the 3-stage scheme, instead of the known 4-stage, using less scarce and safer chemicals. The yield of the target compound with regard to fewer stages higher than in the known method.

The invention is illustrated by examples 1-3.

Example 1. Obtaining N-2-chloroethylamide.

In a three-neck flask equipped with a mechanical stirrer, thermometer and addition funnel is placed 103,1 g (1 mol) of N-acetylethanolamine and 200 ml of benzene. Then the mixture with vigorous stirring cooled in an ice bath to 10oC and added from a dropping funnel 119 g (1 mol) of chloride tiomila with such speed that the temperature of the reaction mixture did not exceed 30oC. By the addition of about one-third of the total number of chloride tiomila reaction mass is much thickens, and with the further addition of the reagent is gradually diluted. After the addition of all chloride tiomila the reaction mixture was stirred for 2 h at room temperature and left overnight.

After exposure to the reaction flask is connected downstream of the fridge and distilled benzene, first under normal pressure, and the East is a career. The residue is a dark thick oil is transferred into a flask of Clausena and vacuum distilled at 110-112oC and 2-3 mm RT.article allocate and 91.2 g of N-2-chloroethylamide. Yield 75%, n2D01,4770,d2401,778; MRD: calc. 29,15; calc. 29,16. The infrared spectrum, in Basel. oil, cm-1: 3300 (N-H), 1630 (amide I band), 1540 (amide II band), 650 (C-CI).

Literature data [2]: I. instrumentation. 135-136 (10); n2D01,4894.

Example 2. Obtain 1,2-bis(N-2-acetylbenzoate)benzene

In a three-neck flask equipped with a mechanical stirrer, addition funnel, reflux condenser and a tube for entry of inert gas, put 22,0 g (0.2 mol) of pyrocatechin, 16,8 g (0.42 mol) of powdery sodium hydroxide, 3 g of TEB and 300 ml of n-butyl alcohol. The reaction mixture is boiled under nitrogen atmosphere with stirring for one hour. Then added dropwise over 1.5 hours to 48.6 (0.4 mol) of N-2-chloroethylamide, after which the reaction mixture is boiled under stirring for 4 hours. Next, the contents of the flask are cooled to room temperature and filtered. From the filtrate butyl alcohol is distilled off in vacuum (20-30 mm RT.CT.) and the residue is subjected to vacuum distillation. Get 42,0 g of 1,2-bis(N-2-acetylbenzoate)benzene with so Kip. 140-146oC when the KTR, in chloroform, cm-1: 3300 (N-H), 1660 (amide I band), 1515 (amide II band). PMR-spectrum , M. D.: 6,99 (4H, o-C6H4), 6,20 (2NH), 4.09 to t (hon2), 3,52 (HSN2NH), 1,98 (HSN3).

Example 3. Obtain 1,2-bis(2-aminoethoxy)benzene.

In odnogolosy flask, equipped with reflux condenser, place of 8.4 g (0.03 mol) of 1,2-bis(N-2-acetylbenzoate)benzene, 15 ml of water and 2.8 g (0.07 mol) of aqueous 40% sodium hydroxide solution. The mixture is boiled on a water bath for 2-3 hours before until a drop of the reaction mixture introduced into dilute hydrochloric acid will not dissolve without residue. Then the reaction mixture is cooled to room temperature and extracted with 100 ml of n-butyl alcohol. Butanolic the extract washed with water and dried over potash. After distillation alcohol at 20-30 mm RT.article gain of 5.3 g of 1,2-bis(2-aminoethoxy)benzene. Output 90,1%. Viscous brown oil. PMR-spectrum , M. D.: 7,01 (4H, o-C6H4), 4,10 t (4 N, hon2), 3,53 (4H, HSN2NH2).

Literature data [1]: neperedavaemaa oil.

The obtained results are illustrated by table data.

The compounds characterized by IR and PMR spectra.

Thus, prelauncher the number of stages and time costs, to use less scarce and more secure reagents, which greatly simplifies hardware design process, reduces fire hazard.

The developed method can be applied both in the laboratory preparative practice, and in industrial production.

Sources of information:

1. L. S. Hodgkinson, V. R. Johnson, S. J. Leigh et al. Formation of Complexes between Aza Derivates of Crown Ethers and Primary Alkylammonium Salts. Part 4. Diaza - 18 - crown - G Derivates. J. C. S. Perkin 1, 1979, 2193-2202.

2. Heyns, K., Bebenburg W. D. Die Umlagerung von N-Nitroso-N-alkylacylamiden. B. 595 [1955], h. 1, 55-65.

Method for producing 1,2-bis(2-aminoethoxy)-benzene, characterized in that pyrocatechin subjected to interaction with N-2-chloroethylamide in the environment of n-butyl alcohol in the presence of base, followed by hydrolysis of the obtained 1,2-bis(N-2-acetyl-aminoethoxy)-benzene aqueous solution of sodium hydroxide.

 

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