RU1768574C - Method of dibromophenol synthesis - Google Patents

Abstract

Field of use: preparation of intermediates for the synthesis of drugs. SUMMARY OF THE INVENTION: Reagent 1: molecular bromine. Reagent 2: sodium hypochlorite 16-25% aqueous solution of CINaO BP. Reagent 3: phenol. Reaction conditions: aqueous medium, 20-40 ° C, equimolar ratio of reagents, reagent supply time 0.5-1 h, reaction time 2.5-5.0 h, aging time of the reaction mass after the reaction 2.5- 5.0 hours. Yield 98-99%.

Description

The invention relates to organic chemistry, and in particular to a process for phenol dibromo derivatives, which are used as a starting material for the synthesis of various classes of organic compounds, including drugs.

A method is known for producing brominated phenol by reacting phenol or halo-phenols with an aqueous solution of HBg containing 20% HCI and a 35% aqueous solution of H2U2 at a temperature of 20-25 ° C, followed by raising the temperature to 50 ° C.

The disadvantage of this method is: the use of an aqueous solution of HBg, which contains up to 20% HCI, which can lead to the formation of not only bromphenol, but also chlorobromophenol, because previously shown that

a mixture of HC with H202 leads to the chlorination of phenol.

A method is known for producing dibromophenol by reacting m-trifluoromethylphenol with molecular bromine at 50 ° C and elevated pressure.

The disadvantages of the method are:

the complexity of the process technology;

the use of unsaturated C2H hydrocarbon to bind bromine in the product

carrying out the reaction under high pressure;

the need for special absorbers for HBr,

low yield, up to 88.7%, of dibromo-phenol;

the need to use up to 100% of the theory of excess bromine.

A method for the bromination of phenol with molecular bromine in excess of bromine is proposed.

hr 00

ate

and

75-400% of theory, at 35-80 ° С using various catalysts (Fe, AI, FeCl2, ReBr3, AlCIs, AlBrs).

The disadvantages of this method are:

carrying out the reaction in excess of bromine up to 400% of theory;

the use of a variety of catalysts, the isolation of which requires special rlpneMtiB tV jle I

There is a known method for producing brompheno-

fI. %%. . G. ..

catch bromine rbwanne m phenol with CIBr in a mixture of immiscible solvents: 1 Шд1Ги halogen-containing hydrocarbon,

The disadvantages of this method are:

the use of various solvents and catalysts;

the need for preliminary synthesis of a brominating agent, CiBr, which is associated with technological difficulties and additional costs.

Closest to the proposed method in terms of technological essence and the achieved result is a method for producing 2,6-dibromophenols by phenol bromination (formula Z-P-SESHCHON) with bromamine of the formula R NBr2 (where, Et, Pr, Bu) at a temperature of -20 to + 50 ° C in the presence of water-immiscible solvents such as CCk CH2CI2, C2HsOC2H5, phCI CeHs, phMe. The desired product is isolated by treating a 2N mother liquor. With a H2S04 solution, the crystallized masses are separated and crystallized from hexane.

The disadvantages of the method (prototype) are:

low yield of dibromophenol (up to 80%);

multi-stage process, since it becomes necessary to create additional technologies and techniques for the preliminary synthesis and regeneration (after the reaction) of the brominating agent, which is associated with additional costs of raw materials and energy resources;

the need for various solvents.

The aim of the invention is to increase yield and simplify process technology.

The goal is achieved by phenol bromination at 20-40 ° C with molecular bromine in an aqueous medium in the presence of an oxidizing agent. As an oxidizing agent, a 16-25% aqueous solution of sodium hypochlorite or a 25-30% aqueous solution of hydrogen peroxide is used, and the process is carried out at a molar ratio of phenol: bromine: oxidizing agent 1: 1.1, for 2.5-5, 0 h, with dosed supply of bromine and an oxidizing agent for 0.5-1.0 h, after which the reaction mass is kept for 2.5-5.0 h, followed by isolation of the target product by conventional methods.

The proposed method in comparison with the prototype allows you to:

increase the yield of the target product from 87 to 99%;

to increase the conversion of bromine to 100% by using hydrogen bromide at the time of its formation for the further bromination of phenol in the presence of oxidizing agents;

to simplify the technology for the preparation of phenol dibromo derivatives by eliminating the preliminary preparation step of the brominating agent, i.e. bromamines (R NBr2) and its recovery after one cycle of work;

replace hard-to-reach brominating agents (R NBr2) with commercially available molecular bromine;

eliminate the use of organic solvents.

The invention is illustrated by the following examples:

Example 1. In the dark, 9.4 g (0.1 mol) of phenol and 10-20 ml of water are placed in a three-necked flask at 30 ° C, and then, while stirring the reaction mixture, 16.0 g (0) are added gradually over 30 minutes , 1 mol) of bromine. After the bromine supply has been completed, 30.0 g (0.1 mol) of a 25% aqueous sodium hypochlorite solution (with an active chlorine content of 150 g-ion / l) is supplied over 45 minutes. The molar ratio of ArOH: Br2: NaOCI is 1: 1: 1. After this, the reaction mixture was stirred for another 3.5 hours and after the specified time the reaction was completed, the desired product was isolated by recrystallization. 25.2 g of dibromophenol are obtained, the yield of which is 99.2% per phenol taken, i.e. 19.9 g of 2,4-dibromophenol (79%) and 6.3 g of 2,6-dibromophenol (20%). Melting point of dibromophenol (from hexane) 53 ° C.

Found,%: C 28.9; H 1.69; VGBZ

SbN40vg2

Calculated,%; C 28.57; H 1.56; Wh 63.49.

Example 2. The phenol bromination reaction is carried out analogously to example 1, but an 18.0% aqueous sodium hypochlorite solution (with an active chlorine content of 110 g-ion / l), 41.5 g (0.1 mol) is used as an oxidizing agent . Received 24.9 g of dibromophenol - 98.0%, i.e. 19.7 g of 2,4-dibromophenol (79%) and 5.2 g of 2,6-dibromophenol (20%).

Example 3, The phenol bromination reaction was carried out analogously to Example 1, but using a 16.0% aqueous solution of sodium hypochlorite (with an active chlorine content of 100 g-ion / L) 44.3 g (0.1 mol) as the oxidizing agent. 24.9 g of dibromophenol 98.0%, i.e. 19.7 g of 2,4-dibromophenol (79%) and 5.2 g of 2,6-dibromophenol (20%).

Example 4, The phenol bromination reaction was carried out analogously to Example 1, but a 30% aqueous solution of hydrogen peroxide 11.33 g (0.1 mol) was used as an oxidizing agent. Received 25.2 g of dibromophenol - 99.2%, i.e. 19.9 g of 2,4-dibromophenol (79%) and 5.3 g of 2,6-dibromophenol (20%).

Example 5. The phenol bromination reaction was carried out analogously to Example 1, but a 28% aqueous solution of hydrogen peroxide 12.2 g (0.1 mol) was used as an oxidizing agent. Received 24.9 g of dibromophenol - 98.0%, i.e. 19.7 g of 2,4-dibromophenol (79%) and

5.2 g of 2,6-dibromophenol (20%).

Example 6. The phenol bromination reaction was carried out analogously to Example 1, but a 25% aqueous solution of hydrogen peroxide 13.6 g (0.1 mol) was used as an oxidizing agent. Received 25.0 g of dibromophenol - 98.5%, i.e. 19.7 g of 2,4-dibromophenol (79%) and

5.3 g of 2,6-dibromophenol (20%). Example 7. The bromination reaction

phenol is carried out analogously to example 1, but at 20 ° C and a reaction time of 5.0 hours. 24.8 g of dibromophenol are obtained, the yield of which is 97.6%.

Example 8. The phenol bromination reaction was carried out analogously to Example 1, at a temperature of 30 ° C and a duration of 2.5 hours. 24.8 g of dibromophenol were obtained, the yield of which was 97.6%.

Example 9. The phenol bromination reaction is carried out analogously to example 1, but

at 40 ° C for a duration of 3.5 hours, 25.2 g of dibromophenol were obtained, the yield of which was 99.2%.

Example 10. The reaction was carried out as in Example 1, but bromine and an oxidizing agent were fed sequentially for 45 minutes. The exposure time after the reaction is 5 hours. Product yield 98%.

Example 11. The reaction was carried out as in Example 10, but the feed time of the reagents was 1 hour, the exposure time was 4.5 hours. The yield was 98.5%.

Example 12. The process is carried out as in Example 1, but the reaction mass is kept for 5 hours. Yield 98%.

Example 13 The process is carried out as in Example 1, but the holding time is 2.5 hours. The yield is 99%.

Claims (1)

The claims A method of producing dibromophenol by phenolation at a temperature of 20-40 ° C with a brominating agent in an aqueous medium in the presence of an oxidizing agent, characterized in that, in order to increase the yield of the target product and simplify the technology, molecular bromine is used as a brominating agent, and as oxidizing agent 16-25% aqueous solution of sodium hypochlorite or 25-30% aqueous solution of hydrogen peroxide, the process is carried out at a molar ratio of phenol: bromine: oxidizing agent 1: 1: 1 for 2.5-5.0 h with dosed supply of bromine and oxidizing agent for 0.5-1 After which the reaction mass is maintained for 2.5-5 hours.