A need exists for a synthetic method of preparing thiophene compounds that are brominated at the 3-position or 4-position of the thiophene ring. Standard procedures are not successful.

This invention provides novel process for brominating the 3-position or 4-position of a thiophene starting material that is unsubstituted in the 3-position or 4-position of the thiophene ring which comprises: reacting said thiophene starting material with bromine in acetic acid in the presence of sodium acetate.

The thiophene starting material may be substituted at any of its four carbon atoms, provided that either the 3-position or 4-position remains unsubstituted. It will be appreciated that the 2-position and the 5-position, if unsubstituted in the starting material, will be brominated before the 3-position and 4-position. The reaction can be performed in acetic acid or propanoic acid at a reaction temperature in the range of 0°C to the boiling point of the solvent, preferably at a temperature in the range 60-80°C. Other bases, for example potassium acetate, can be used in place of sodium acetate.

A useful application of the bromination process is as the first step in a two step process for preparing thiophene compounds that are brominated in the 3-position or 4-position and unsubstituted in the 5-position, as illustrated in Example 2 below.

Accordingly, the invention also provides a two step process for preparing a thiophene compound that is brominated in the 3-position or 4-position and unsubstituted in the 5-position, which comprises: a) reacting a thiophene starting material that is unsubstituted in the 5-position and unsubstituted in the 3-position or 4-position with bromine in acetic acid in the presence of sodium acetate to produce an intermediate that is brominated in the 5-position and in the 3- position or 4-position, and b) reacting the intermediate produced in step a with a lithium source to remove the bromine from the 5- position.

Step b in the above described process can be performed in a variety of ethers, such as THF, diethylether, or diglyme, or in a hydrocarbon solvent, such as hexane or pentane. The reaction temperature can be in the range-10°C to-100°C. The lithium source can be n-butyl lithium, t-butyl lithium, s-butyl lithium, or phenyl lithium.

Example 1 3- (2-chloro-6-fluorophenyl)-5- (3-methyl-4,5- dibromothien-2-yl) 1-methyl [1,2,4] triazole Bromine (2.7 mL) was added to a solution of 3- (2-chloro- 6-fluorophenyl)-5- (3-methyl-5-bromothien-yl) 1-methyl [1,2,4] triazole (10.0g), sodium acetate (4.25g) in acetic acid (100 mL) under a nitrogen atmosphere. This brown suspension was heated at 70°C for 2. Oh. After cooling, diethyl ether (500 mL) was added and the reaction was made basic with saturated sodium bicarbonate. The ether layer was washed with NaHCO3 (sat.), water, dried (Na2SO4), filtered and concentrated to yield 12g of crude solid. Trituration with hexane gave 3- (2-chloro-6-fluorophenyl)-5- (3-methyl-4,5-

dibromothien-2-yl) 1-methyl [1,2,4] triazole as white solid (10g, 83% yield). MP 137-138 °C ; Anal. Calcd. For C14H9Br2ClFN3S ; C, 36.12 ; H, 1.95; N, 9.03; S, 6.89.

Found; C, 36.70 ; H, 2.00; N, 8.68 ; S, 6.78.

The product of Example 1 is useful as an insecticide and also as an intermediate in preparation of the insecticide 3- (2-chloro-6-fluorophenyl)-5- (3-methyl-4- bromothien-2-yl) 1-methyl 1,2,4 triazole, as demonstrated in the following Example 2.

Example 2 3- (2-chloro-6-fluorophenyl)-5- (3-methyl-4- bromothien-2-yl) 1-methyl [1,2,4] triazole n-Butyl lithium (6.04 mL, 2.5mmol) was slowly added over a 15 min period to 3- (2-chloro-6-fluorophenyl)-5- (3- methyl-4,5-dibromothien-2-yl) 1-methyl [1,2,4] triazole (7.0g) in THF (100 mL) at-70 °C under a nitrogen atmosphere and stirred for l. Oh. After the addition of the distilled water, the reaction was allowed to warm to 25 °C. The reaction mixture was extracted with diethyl ether (3 x 100 mL). The combined ether extracts was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated to crude solid. This was chromatographed on silica gel (EtOAc/Hexane, 1: 1) to give 5. Og (86% yield) 3- (2-chloro-6-fluorophenyl)-5- (3-methyl- 4-bromothien-2-yl) 1-methyl [1,2,4] triazole as white solid. MP 111-112 °C; Anal. Calcd. For C14Hl0BrClFN3S: C, 43.49; H, 2.61; N, 10.87; S, 8.29. Found; C, 43.79; H, 2.66; N, 10.95; S, 8.28.