PROCESS FOR THE PREPARATION OF 5-BROMO-1,2,3-TRICHLOROBENZENE

Abstract

The present invention relates to a process for the preparation of a compound of formula I (I), comprising reacting a compound of formula II (II), with a brominating agent in the presence of an acidic catalyst to a compound of formula III (III), and reacting the compound of formula III in tetrahydrofuran or 2-methyl-tetrahydrofuran with potassium tert-butoxide to a compound of formula I.

##STR00001##

Claims

1. A process for the preparation of a compound of formula I ##STR00013## comprising a) reacting a compound of formula II ##STR00014## with a brominating agent in the presence of an acidic catalyst to a compound of formula III, ##STR00015## and b) reacting the compound of formula III in tetrahydrofuran or 2-methyl-tetrahydrofuran with potassium tert-butoxide to a compound of formula I.

2. A process according to claim 1, wherein the acidic catalyst is selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid and Lewis acids or prepared in situ by mixing bromine with iron powder.

3. A process according to claim 2, wherein the Lewis acid is selected from iron (III) bromide, aluminum bromide, boron trifluoride etherate and titanium tetrachloride.

4. A process according to claim 1, wherein the brominating agent is selected from bromine and N-bromo succinimide.

5. A process according to claim 1, wherein the compound of formula III is reacted in tetrahydrofuran with potassium tert-butoxide to a compound of formula I.

6. A process according to claim 1 comprising a) reacting a compound of formula II ##STR00016## with a brominating agent selected from bromine and N-bromo succinimide in the presence of an acidic catalyst selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid and Lewis acids or prepared in situ by mixing bromine with iron powder, to form a compound of formula III, ##STR00017## and b) reacting the compound of formula III in tetrahydrofuran with potassium tert-butoxide to a compound of formula I.

Description

PREPARATORY EXAMPLES

Example 1: Preparation of 1-bromo-2,3,4-trichloro-benzene of formula III

[0018] ##STR00011##

[0019] To a solution of 1,2,3-trichlorobenzene (1.5 g, 8.3 mmol) in tetrachloromethane (21 ml) was added iron powder (0.92 g, 17 mmol). To this suspension was added bromine (2.7 g, 17 mmol) and the resulting mixture was heated at 100° C. for 18 hours. The reaction was quenched by addition of a mixture of a saturated aqueous NaHCO.sub.3 and 1M Na.sub.2S.sub.2O.sub.3. The resulting mixture was filtered through celite, layers were separated and aqueous phase was extracted with dichloromethane (2×). The combined organic layers were dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure. The crude product was purified by silica gel chromatography (eluting with pure heptane) to afford 1-bromo-2,3,4-trichloro-benzene (1.68 g) as a white powder.

[0020] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.50 (d, J=8.8 Hz, 1H), 7.27 (d, J=8.8 Hz, 1H).

[0021] Alternatively, the compound of formula III can be also obtained by carrying out the following procedure:

[0022] 1,2,3-trichloro-benzene was heated to 60° C. and iron (III) bromide (1.66 g, 5.5 mmol) was added followed by bromine (1.77 g, 11 mmol). The reaction mixture was stirred at 60° C. for 3 hours, cooled to ambient temperature, diluted with dichloromethane and quenched by pouring into a mixture of a saturated aqueous NaHCO.sub.3 and 1M Na.sub.2S.sub.2O.sub.3. The resulting mixture was filtered through celite, layers were separated and the aqueous phase was extracted with dichloromethane (2×). The combined organic layers were dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure to afford pure 1-bromo-2,3,4-trichloro-benzene (2.81 g) as a beige powder.

Example 2: Preparation of 5-bromo-1,2,3-trichloro-benzene of formula I

[0023] ##STR00012##

[0024] To a solution of 1-bromo-2,3,4-trichloro-benzene (50.0 g, 192 mmol) in dry tetrahydrofuran (25 ml) was added 1.0M KOtBu in THF (52 g, 58 mmol) and the resulting solution was stirred at ambient temperature for 1 hour. The reaction was acidified with aqueous HCl and the aqueous phase was extracted with dichloromethane (2×). The combined organic layers were dried over Na.sub.2SO.sub.4 and evaporated under reduced pressure. The obtained crude product (49.5 g) contains a mixture of 5-bromo-1,2,3-trichloro-benzene and 1-bromo-2,3,4-trichloro-benzene in a ratio 5.1:1. Both substances can be separated by distillation under reduced pressure and 1-bromo-2,3,4-trichloro-benzene can then be recycled.

[0025] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.55 (s, 2H).