Reaction #2446131

Reaction equation

2-iodo-5-methylbenzoic acid

1,2,3-triazole

trans-N,N′-dimethylcyclohexane-1,2-diamine

→

2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic Acid

Solvents

water

DMF

Conditions

Workup

1. 1
   TemperatureThe reaction was cooled to room temperature
2. 2
   Washwashed with EtOAc
3. 3
   Extractionextracted with EtOAc
4. 4
   DryingThe organic layer was dried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   OtherThe residue was purified by gradient elution on SiO2 (0 to 10% MeOH in water with 0.1% AcOH)
8. 8
   Otherto give the
9. 9
   Washfaster eluting 2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid B-2

Procedure

A solution of 2-iodo-5-methylbenzoic acid (4.0 g, 15.3 mmol) in DMF (10 mL) was treated with 1,2,3-triazole (2.1 g, 30.5 mmol), CsCO3 (9.95 g, 30.5 mmol), CuI (0.145 g, 0.76 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.43 g, 3.05 mmol). The mixture was heated at 120° C. for 10 min in a microwave reactor. The reaction was cooled to room temperature, diluted with water, and washed with EtOAc. The aqueous phase was acidified with 1N HCl and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by gradient elution on SiO2 (0 to 10% MeOH in water with 0.1% AcOH) to give the faster eluting 2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid B-2, followed by the undesired regioisomer isomer, 1-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid. Data for B-2: 1HNMR (500 MHz, DMSO-d6) δ 12.98 (br s, 1H), 8.04 (s, 2H), 7.72-7.45 (m, 3H), 2.41 (s, 3H) ppm.

Source