Hydrochloric Acid → 5-(4-Bromo-3,5-dimethylphenyl)-2H-1,2,3,4-tetrazole

HRID 2170939Notes

Reaction equation

HRID 2170939 reaction equation
[Br:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:11].[N-:12]=[N+:13]=[N-:14].[Na+].[Cl-].C([NH+](CC)CC)C.Cl>C1(C)C(C)=CC=CC=1>[Br:1][C:2]1[C:3]([CH3:11])=[CH:4][C:5]([C:6]2[N:12]=[N:13][NH:14][N:7]=2)=[CH:8][C:9]=1[CH3:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 110850704-Bromo-3,5-dimethyl-benzonitrileHCID 12698378Triethylazanium chloride

Product 1

HCID 866972675-(4-Bromo-3,5-dimethylphenyl)-2H-1,2,3,4-tetrazole

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
115 °C

Procedure

5-(4-Bromo-3,5-dimethylphenyl)-2H-tetrazole may be obtained as follows: To a solution of 135 g (0.642 mol) 4-bromo-3,5-dimethylbenzonitrile in 960 mL anhydrous xylene, 141.6 g (1.028 mol) sodium azide and 10.48 g (1.028 mol) triethylammonium chloride is added. The mixture is heated to 115° C. and stirred overnight. After cooling to r.t. the reaction mixture is poured into 2 L of ice water and the pH is adjusted to pH=1 by acidification with conc. aq. hydrochloric acid. Stirring is continued for 1 h. The crude product is filtered off, washed with n-hexane (lx 500 mL) and water (3×600 mL) and dried to yield the intermediate 5-(4-bromo-3,5-dimethylphenyl)-2H-tetrazole. 166 g (0.29 mol) 5-(4-bromo-3,5-dimethylphenyl)-2H-tetrazole is dissolved in 3.2 L DMF and cooled to −10° C., before 305 g (2.15 mol) iodomethane is added. Afterwards, a solution of 71.3 g (0.742 mol) sodium tert-butoxide in 810 mL anhydrous THF is added slowly over a period of 25 min whilst keeping the temperature constant. After full conversion the reaction mixture is warmed to r.t. and poured into 1 L water. The resulting suspension is stirred for an additional hour at r.t. The crude product is filtered off, washed with water (3×1 L) and dried. After recrystallization from acetonitrile/water (1:1) mixture 90.8 g of the title compound is obtained as off white solid.

Workup

  1. temperatureAfter cooling to r.t. the reaction mixture
  2. stirringStirring
  3. waitis continued for 1 h
  4. filtrationThe crude product is filtered off
  5. washwashed with n-hexane (lx 500 mL) and water (3×600 mL)
  6. customdried

Sources & evidence

ORD record
ord-2743a8c6475641b99bb846c8354efcba
Source dataset
uspto-grants-2015_06
Patent number
US09051289B2

Reaction notes

Loading…