Diethyl Ether → N-(4-Hexylphenyl)-4,5-dihydro-1,3-thiazol-2-amine

HRID 2232412Notes

Reaction equation

HRID 2232412 reaction equation
[CH2:1]([C:7]1[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].Cl[CH2:15][CH2:16][N:17]=[C:18]=[S:19].C(OCC)C>C1(C)C=CC=CC=1>[CH2:1]([C:7]1[CH:8]=[CH:9][C:10]([NH:11][C:18]2[S:19][CH2:15][CH2:16][N:17]=2)=[CH:12][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 363824-HexylanilineHCID 1386612-Chloroethyl Isothiocyanate

Product 1

HCID 195219N-(4-Hexylphenyl)-4,5-dihydro-1,3-thiazol-2-amine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
50 °C

Procedure

A 2 liter, 3-neck round bottom flask fitted with magnetic stirrer, addition funnel, argon gas inlet and thermometer was charged with 4-hexylaniline (65.0 g, 0.367 m) dissolved in 500 ml reagent toluene. To this stirred solution, was added dropwise a solution of β-chloroethylisothiocyanate (53.5 g, 0.441 m, 1.2 eq.) in 175 ml toluene at room temperature. No significant exotherm was noted. After the addition was completed, the reaction mixture was warmed to 50° C. for 19 hours. The reaction was cooled to room temperature and the toluene removed on the rotary evaporator to give an orange, semi-solid residue which was stirred with 900 ml diethyl ether (Et2O). The resulting slurry of off-white solid was cooled in an ice water bath and the solid filtered, washed with cold Et2O, and dried (filter suction, desiccator) to give the slightly impure hydrochloride salt of the desired aminothiazoline. The HCl salt was neutralized by adding the salt to a cold, stirred solution of sodium hydroxide (14.7 g, 0.367 m) in 1200 ml water layered with Et2O. After neutralization, the ether layer was separated and the aqueous layer was extracted with Et2O four times. The combined Et2O extracts were washed with water twice and with a saturated NaCl solution once, dried (MgSO4), and evaporated under vacuum to afford 90.0 g of crude, freebase product as a waxy, off-white solid. The crude material was recrystallized from 900 ml hexane to give 73.0 g (76%) product in two crops as small, off-white platelets. m.p. 77°-79° C.

Workup

  1. customA 2 liter, 3-neck round bottom flask fitted with magnetic stirrer, addition funnel, argon gas inlet
  2. additionAfter the addition
  3. temperatureThe reaction was cooled to room temperature
  4. customthe toluene removed on the rotary evaporator
  5. customto give an orange, semi-solid residue which
  6. temperatureThe resulting slurry of off-white solid was cooled in an ice water bath
  7. filtrationthe solid filtered
  8. washwashed with cold Et2O
  9. customdried
  10. filtration(filter suction, desiccator)

Sources & evidence

ORD record
ord-58c4f34cb8c2422a89f3ff3198dce0aa
Source dataset
uspto-grants-1988_11
Patent number
US04788209

Reaction notes

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