Carbon Disulfide → 4-Isopropyl-3-isothiocyanatotoluene

HRID 62041Notes

Reaction equation

HRID 62041 reaction equation
[CH:1]([C:4]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:5]=1[NH2:6])([CH3:3])[CH3:2].[C:12](=S)=[S:13].C(N(CC)CC)C.C(N=C=NC(C)C)(C)C>C(#N)C.O>[CH:1]([C:4]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:5]=1[N:6]=[C:12]=[S:13])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6348Carbon DisulfideHCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 205638272-Isopropyl-5-methylaniline

Product 1

HCID 1186751304-Isopropyl-3-isothiocyanatotolueneYield 48.4%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
40 °C

Procedure

To 2-isopropyl-5-methylaniline (1.0 g, 6.7 mmol) in a 25 mL vial equipped with a stir bar, Vigreux column, and nitrogen was added carbon disulfide (3.0 mL, 50 mmol). The reaction was heated to 40° C. and cooled immediately. To this solution was added triethylamine (0.93 mL, 6.7 mmol). The reaction was heated to 50° C. for 90 minutes and cooled to room temperature overnight. The reaction mixture was transferred to a 100 mL round-bottomed flask and concentrated. The residue was taken up in acetonitrile (33.5 mL) and treated with N,N′-diisopropycarbodiimide (1.04 mL, 6.70 mmol). The reaction was stopped after a few h and concentrated. Purification by flash column chromatography using 2.5-5% ethyl acetate/hexanes as eluent provided a mixture of products. Re-purification by reversed phase column chromatography using 5-100% acetonitrile/water as eluent provided the title compound (65% in dichloromethane, 0.62 g, 31%), which was used without further purification: IR (thin film) 2963 (m), 2924 (m), 2869 (w), 2089 (vs), 1611 (w), 1501 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ 7.16 (d, J=8.6 Hz, 1H), 7.09-7.03 (m, 2H), 3.19 (h, J=6.8 Hz, 1H), 2.30 (s, 3H), 1.24 (d, J=6.9 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 141.50, 136.70, 134.59, 128.84, 128.58, 127.12, 126.05, 29.20, 22.83, 20.62.

Workup

  1. temperaturecooled immediately
  2. temperatureThe reaction was heated to 50° C. for 90 minutes
  3. temperaturecooled to room temperature overnight
  4. customThe reaction mixture was transferred to a 100 mL round-bottomed flask
  5. concentrationconcentrated
  6. concentrationconcentrated
  7. customPurification by flash column chromatography
  8. customprovided
  9. additiona mixture of products

Sources & evidence

ORD record
ord-9966b63b50a040029d674fa51f86ee4e
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Reaction notes

Loading…