(E)-3-(3-((phenylamino)sulfonyl)phenyl)acrylic acid

Preparation of (E)-3-(3-((phenylamino)sulfonyl)phenyl)acrylic acid (6)

Malonic acid (145 g, 1.4 mol) was added in batches to a solution of 3-formyl-N-phenylbenzenesulfonamide 5 (240 g, 0.9 mol) and piperidine (18 mL, 0.2 mol) in pyridine (700 mL), then the mixture was stirred at 105–110 °C for 8.5 h. When TLC analysis indicated the disappearance of 5, the reaction mixture was cooled to ambient temperature and slowly poured into chilled 5% aqueous solution of sodium hydroxide (2.4 L) below 20 °C (pH: 9–10). The reaction mixture was washed with EA (1.2 L), and the separated organic layer was extracted with 5% aqueous solution of sodium hydroxide (600 mL). The aqueous layers were combined and cooled to 10–20 °C, then it was acidified slowly with 50% sulfuric acid (600 mL) below 20 °C (pH: 1–2). After the solution stirred for an additional 30 min at 15–20 °C, the solid obtained was collected by filtration and then washed with water (2.4 L) followed by n-hexane (1 L). The filter cake was dried in a vacuum oven at 50 °C to afforded colorless solid (E)-3-(3-((phenylamino)sulfonyl)phenyl)acrylic acid (244 g, 83%). mp 154–156 °C. 1H NMR (400 MHz, DMSO-d6) δ = 12.62 (bs, 1H), 10.32 (s, 1H), 8.01 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.63–7.56 (m, 2H), 7.24 (m, 2H), 7.11–7.01 (m, 3H), 6.55 (d, J = 16.0 Hz, 1H). MS (ESI):m/z = 326.0 [M+Na] +.

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KHAJURAHO, MADHYA PRADESH, INDIA

Khajuraho Group of Monuments

The Khajuraho Group of Monuments is a group of Hindu and Jain temples in Madhya Pradesh, India, about 175 kilometres southeast of Jhansi. They are one of the UNESCO World Heritage Sites in India.Wikipedia

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3-Formyl-N-phenylbenzenesulfonamide

Preparation of 3-Formyl-N-phenylbenzenesulfonamide (5)

Pyridine (96 mL, 1.5 mol) was added to a solution of aniline (118 mL, 1.3 mol) in EA (600 mL), and the mixture was stirred at 0–5 °C. Then the solution of 3-formylbenzenesulfonyl chloride 4 (200 g, 1.0 mol) in EA (400 mL) was added slowly to the reaction mixture over 1.5 h while maintaining the reaction temperature below 5 °C. The solution was stirred at 0–5 °C for 1 h and then at ambient temperature for 19 h. When the reaction was deemed to be complete with no 4 detected by TLC, the reaction mixture was washed with a 10% aqueous solution of hydrochloric acid (two portions of 500 mL) followed by washing with water (500 L), 5% aqueous solution of sodium bicarbonate (500 mL), and then brine (500 mL); dried with sodium sulfate anhydrous; filtered; and concentrated to afford yellow solid 3-formyl-N-phenylbenzenesulfonamide (242 g, 93%). Crude 5was used directly into next step. A sample of purified 5 as a white solid was analyzed as follows.

1H NMR (CDCl3, 400 MHz) δ = 10.38 (s, 1H), 10.00 (s, 1H), 8.29 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.62 (t, J = 7.8 Hz, 1H), 7.27–7.23 (m, 2H), 7.16–7.01 (m, 3H).

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KHAJURAHO, MADYA PRADESH, INDIA

Khajuraho Group of Monuments

The Khajuraho Group of Monuments is a group of Hindu and Jain temples in Madhya Pradesh, India, about 175 kilometres southeast of Jhansi. They are one of the UNESCO World Heritage Sites in India.Wikipedia

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3-Formylbenzenesulfonyl Chloride

3-Formylbenzenesulfonyl Chloride 

A suspension of bisulphite adduct 3 (300 g, 1.4 mol) and anhydrous potassium sulfate powder (174 g; 1.0 mol) in DCM (3 L) was stirred at 0–5 °C, and chlorosulfonic acid (560 mL, 8.6 mol) was added dropwise into the suspension while maintaining the temperature below 30 °C (caution: highly exothermic). When the addition completed over 6 h, the reaction mixture was further stirred at 25–30 °C for 22 h. After the completion of the reaction, monitored by TLC, the reaction mixture was slowly poured into crushed ice (3 kg) and stirred for 1 h. The aqueous phase was removed, and the organic phase was washed with water (2 L) followed by 5% aqueous solution of sodium bicarbonate (1 L) and brine (1 L) before being dried over anhydrous sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuum (10–15 Torr, pot temperature of 20 °C) to afford crude 4

The crude 4 was dissolved in toluene (300 mL) and then the solution was taken ahead as such for the purification. The silica gel (1.2 kg) was carefully poured into a column (diam: 10 cm), and compressed air was used to pack the column. After 1 h, a portion of the solution (one-sixth of the total) was added and pressed into the dry silica gel using compressed air. When added solution was all deposited on silica, another portion was added, and repeated until all six portions were added. After the portion-wise addition, the column was eluted with toluene (7.3 L), and the eluent was concentrated in vacuum (10–15 Torr, pot temperature below 35 °C) to afford light yellow oil 3-formylbenzenesulfonyl chloride (203 g, 69%). (caution: 3-formylbenzenesulfonyl chloride 4 was more likely to convert into strong-polarity impurities when the pot temperature was higher than 40 °C).

1H NMR (CDCl3, 400 MHz) δ = 10.13 (s, 1H,), 8.53 (s, 1H), 8.31–8.26 (m, 2H), 7.85 (t, J = 8.0 Hz, 1H).

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Sodium α-Hydroxybenzenemethanesulfonic Acid

Sodium α-Hydroxybenzenemethanesulfonic Acid 

Sodium metabisulfite (627 g, 3.3 mol) was dissolved in water (1.5 L), and a small amount of insoluble substance was filtered off. The filtrate was added to a solution of benzaldehyde (500 g, 4.7 mol) in EtOH (3 L) over 3 h under ambient temperature and then the reaction mixture was stirred at 45–50 °C under an atmosphere of argon overnight. After 18 h, the reaction mixture was sampled and deemed to be complete with no benzaldehyde being detected by TLC. The heterogeneous reaction mixture was cooled to ambient temperature, stirred for 4 h, and then isolated by vacuum filtration. The product cake was washed with EtOH (two portions of 200 mL) to give the product bisulphite adduct as a white solid (907 g, 92%), after drying under vacuum at 50 °C, mp 150–152 °C, decomposition, (lit. 153–156 °C, decomposition).

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KHAJURAHO, MADHYA PRADESH, INDIA

Khajuraho Group of Monuments

The Khajuraho Group of Monuments is a group of Hindu and Jain temples in Madhya Pradesh, India, about 175 kilometres southeast of Jhansi. They are one of the UNESCO World Heritage Sites in India.Wikipedia

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