4-MethoxyThiophenol (AlfaAesar) ≥97%, A16009
Isatin (Sigma Aldrich), 98%, 114618
Formaldehyde Solution 37% (Sigma Aldrich), 15512
Trifluoroacetic acid (SD fine Chemicals Ltd), 98%, 40508L05 

The mixture of 4-methoxy thiophenol (100 mg, 1 mmol), formaldehyde (80 µl, 3 mmol) and isatin (105 mg, 1 mmol) in 0.1% TFA in water (5 ml) was stirred at 80 °C for 30 min. Completion of the reaction was monitored by TLC (20% EtOAc in n-hexane). Reaction mixture was cooled to room temperature and was neutralized with saturated NaHCO₃ solution and extracted with EtOAc (50 mL × 2). The combined organic layer was dried over anhydrous sodium sulphate and evaporated on vacuo rotavapor to get crude product. Crude product was purified by silica gel column chromatography (mesh 100-200) using EtOAc: hexane as a mobile phase to get product in 95% yield.

• This work provides green and efficient protocol for coupling of various thiophenols, formaldehyde and simple, substituted isatins in water. 
• Reaction proceeds through in situ formation of thiophenylmethylium cation intermediate.

1-(((4-Methoxyphenyl)thio)methyl)indoline-2,3-dione: orange red solid; m.p: 109-111°C
¹H NMR: (CDCl₃, 400 MHz): δ 7.63 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.13 (m, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.0 Hz, 2H), 4.98 (s, 2H), 3.76 (s, 3H).
¹³C NMR (CDCl₃, 100 MHz): δ 182.6, 160.6, 157.2, 149.4, 138.3, 136.2, 125.3, 124.1, 121.6, 117.7, 115.0, 112.0, 55.4, 45.8.
IR (CHCl₃): 3447, 2921, 1738, 1611, 1590, 1493, 1469, 1363, 1339, 1286, 1267, 1171, 1094, 1022 cm^-1.
ESIMS: m/z 300.0 [M+H]⁺.
HR-ESIMS: m/z 300.0661 calculated for C₁₆H₁₃NO₃S+H⁺ (300.0689)

Mudududdla, R.; Sharma, R.; Guru, S.K.; Kushwaha, M.; Gupta, A.P.; Bharate, S.S.; Aravinda, S.; Kant, R.; Bhushan, S; Vishwakarma, R.A.; Bharate, S.B. Trifluoroacetic acid catalyzed thiophenylmethylation and thioalkylmethylation of lactams and phenols via domino three-component reaction in water.  RSC Adv. 2014, 4, 14081-14088. http://dx.doi.org/10.1039/c3ra47874b