Efficient and Novel Method for Thiocyanation of Aromatic and Hetero-aromatic Compounds Using Bromodimethylsulfonium Bromide and Ammonium Thiocyanate

Abstract

Various aromatic and heteroaromatic compounds have been efficiently thiocyanated by using a novel combination of bromodimethylsulfonium bromide (BDMS) and ammonium thiocyanate.

bromodimethylsulfonium bromide - ammonium thiocyanate - aromatic thiocyanate - heteroaromatic thiocyanate - thiocyanation

References and Notes

See reviews:

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9

Preparation of Bromodimethylsulfonium Bromide (BDMS):^7a Dimethyl sulfide (3.69 mL, 50 mmol) was taken in anhyd CH₂Cl₂ (10 mL) into a 150-mL conical flask. Then, bromine (2.56 mL, 50 mmol) dissolved in anhyd CH₂Cl₂ (10 mL) was added slowly into the above solution at ice-bath temperature over a period of 10 min. During the addition, light orange crystals of bromodimethylsulfonium bromide begin to separate out. After the addition of bromine was complete, the crystals of bromodimethylsulfonium bromide were collected by filtration, washed with anhyd hexane and dried under vacuum; yield: 8.6 g (77%); mp 80-82 °C (lit.^7a 81-82 °C).

10

General Experimental Procedure for Thiocyanation: To a yellow suspension of BDMS (1.66 g, 7.5 mmol) and ammonium thiocyanate (1.14 g, 15 mmol) in anhyd MeCN (50 mL) the substrate (5 mmol) was added immediately in one portion. The reaction mixture was stirred at r.t. until complete consumption of starting material as observed by TLC. After completion of the reaction, it was quenched with sat. solution of NaHCO₃ (50 mL) and the solid residue was removed by filtration and the residue was washed with EtOAc. The organic layer was separated, washed with H₂O (50 mL), brine (50 mL) and dried over anhyd Na₂SO₄ and concentrated under reduced pressure to give the crude thiocyanato product. Pure product was obtained after column chromatography (silica gel, mesh size 60-120, eluent EtOAc-hexane, 10:90).
Caution!! Reaction generates odorous dimethyl sulfide. All operations should be carried out in well-ventilated hood. The effluent should be treated with bleach before disposal.
Spectral Data for Thiocyanated Products
2-Methyl-4-thiocyanatophenol (1a): solid; mp 70-72 °C (lit.¹¹ 71-72 °C). ¹H NMR (60 MHz, CDCl₃): δ = 3.24 (s, 3 H), 6.14 (br s, 1 H), 6.64-7.25 (m, 3 H). IR (KBr): 3378, 2925, 2159 (SCN), 1597, 1495, 1275, 815 cm^-1.
4-Thiocyanatophenol (2a): solid; mp 51-52 °C (lit.¹¹ 52-53 °C). ¹H NMR (60 MHz, CDCl₃): δ = 5.62 (br s, 1 H), 6.79 (d, J = 8.4 Hz, 2 H), 7.36 (d, J = 8.4 Hz, 2 H). IR (KBr): 3363, 3009, 2158 (SCN), 1585, 1492, 1212, 828, 756 cm^-1.
1-Methoxy-4-thiocyanatobenzene (3a): solid; mp 33-34 °C (lit.¹² 33-34 °C). ¹H NMR (60 MHz, CDCl₃): δ = 3.74 (s, 3 H), 6.69 (d, J = 9.0 Hz, 2 H), 7.31 (d, J = 9.0 Hz, 2 H). IR (KBr): 2985, 2155 (SCN), 1587, 1475, 1267, 818, 712 cm^-1.
1-Methoxy-4-thiocyanatonaphthalene (4a): solid; mp 104-106 °C (lit.^4c 106-107 °C). ¹H NMR (60 MHz, CDCl₃): δ = 4.08 (s, 3 H), 6.71-6.75 (m, 1 H), 7.62-8.29 (m, 5 H). IR (KBr): 2978, 2152 (SCN), 1591, 1271, 1063, 807, 771 cm^-1.
1-Methoxy-2-methyl-4-thiocyanatobenzene (5a): oil (lit.^4c oil). ¹H NMR (60 MHz, CDCl₃): δ = 2.50 (s, 3 H), 3.91 (s, 3 H), 6.81-7.16 (m, 3 H). IR (KBr): 2990, 2153 (SCN), 1596, 1485, 1260, 880 cm^-1.
4-Thiocyanatobenzenamine (6a): solid; mp 50-52 °C (lit.^5f 51-52 °C). ¹H NMR (60 MHz, CDCl₃): δ = 3.82 (br s, 2 H), 6.67 (d, J = 8.8 Hz, 2 H), 7.33 (d, J = 8.8 Hz, 2 H). IR (KBr): 3403, 3350, 2137 (SCN), 1627, 1591, 1432, 818 cm^-1.
2-Methyl-4-thiocyanatobenzenamine (7a): solid; mp 70-71 °C (lit.¹³ 70-71 °C). ¹H NMR (60 MHz, CDCl₃): δ = 2.44 (s, 3 H), 3.75 (br s, 2 H), 6.43-6.62 (m, 2 H), 7.18-7.52 (m, 1 H). IR (KBr): 3354, 3243, 2145 (SCN), 1628, 1592, 1492, 1298, 821 cm^-1.
2,6-Dimethyl-4-thiocyanatobenzenamine (8a): solid; mp 85-87 °C (lit.¹⁴ 87-88 °C). ¹H NMR (60 MHz, CDCl₃): δ = 2.44 (s, 6 H), 3.87 (br s, 2 H), 6.62 (s, 1 H), 7.22 (s, 1 H). IR (KBr): 2928, 2147 (SCN), 1615, 1592, 1460, 1288 cm^-1.
N , N -Dimethyl-4-thiocyanatobenzenamine (9a): solid; mp 72-74 °C (lit.^5f 73-74 °C). ¹H NMR (60 MHz, CDCl₃): δ = 2.99 (s, 6 H), 6.76 (d, J = 9.0 Hz, 2 H), 7.51 (d, J = 9.0 Hz, 2 H). IR (KBr): 2922, 2137 (SCN), 1586, 1503, 1362, 1077, 802 cm^-1.
N -Benzyl- N -methyl-4-thiocyanatobenzenamine (10a): solid; mp 68-70 °C. ¹H NMR (60 MHz, CDCl₃): δ = 3.07 (s, 3 H), 4.57 (s, 2 H), 6.69 (d, J = 9.0 Hz, 2 H), 7.05 (s, 5 H), 7.39 (d, J = 9.0 Hz, 2 H). IR (KBr): 3014, 2144 (SCN), 1599, 1460, 1023, 824 cm^-1. Anal. Calcd for C₁₅H₁₄N₂: C, 70.83; H, 5.55; N, 11.01. Found: C, 70.85; H, 5.54; N, 10.98.
N , N -Diallyl-4-thiocyanatobenzenamine (11a): oil; ¹H NMR (60 MHz, CDCl₃): δ = 3.78-3.97 (m, 4 H), 4.96-5.26 (m, 4 H), 5.55-6.06 (m, 2 H), 6.63 (d, J = 9.0 Hz, 2 H), 7.35 (d, J = 9.0 Hz, 2 H). IR (KBr): 3082, 2916, 2148 (SCN), 1641, 1591, 1504, 1238, 811 cm^-1. Anal. Calcd for C₁₃H₁₄N₂S: C, 67.79; H, 6.13; N, 12.16. Found: C, 67.82; H, 6.15; N, 12.18.
2-Amino-6-methoxybenzothiazole (12a): solid; mp 158-160 °C (lit.¹⁵ 161-162 °C). ¹H NMR (60 MHz, CDCl₃): δ = 3.82 (s, 3 H), 5.05 (br s, 2 H), 6.80-7.53 (m, 3 H). IR (KBr): 3435, 3312, 1596, 1230 cm^-1.
2-Amino-6-methylbenzothiazole (13a): solid; mp 130-132 °C (lit.¹⁶ 131-132 °C). ¹H NMR (60 MHz, CDCl₃): δ = 2.23 (s, 3 H), 5.26 (br s, 2 H), 6.92-7.69 (m, 3 H). IR (KBr): 3325, 3413, 1590 cm^-1.
2-Amino-6-bromobenzothiazole (14a): solid; mp 212-213 °C (lit.¹⁶ 213-214 °C). ¹H NMR (60 MHz, CDCl₃): δ = 4.93-5.31 (br s, 2 H), 7.32-7.85 (m, 3 H). IR (KBr): 3320, 3430, 1605 cm^-1.
2-Methyl-3-thiocyanato-1 H -indole (15a): solid; mp 101-102 °C (lit.^5f 102-103 °C). ¹H NMR (60 MHz, CDCl₃): δ = 2.50 (s, 3 H), 7.70-7.75 (m, 3 H), 7.64-7.69 (m, 1 H), 8.56 (br s, 1 H). IR (KBr): 3323, 3061, 2152 (SCN), 1614, 1583, 1408, 1228, 741 cm^-1.
2-Thiocyanato-1 H -pyrrole (16a): oil (lit.^5f oil). ¹H NMR (60 MHz, CDCl₃): δ = 6.26 (m, 1 H), 6.61 (m, 1 H), 6.95 (m, 1 H), 8.83 (br s, 1 H). IR (neat): 3340, 2952, 2159 (SCN), 1530, 1422, 1029, 737 cm^-1.
2-Thiocyanatothiophene (17a): oil (lit.¹⁷ oil). ¹H NMR (60 MHz, CDCl₃): δ = 7.50-8.12 (m, 3 H). IR (neat): 3012, 2158 (SCN), 1412, 1215, 850, 728 cm^-1.

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