N-(Tetrahydro-2-oxo-3-thienyl)-acetamide

Preparation

Add hydrobromic acid to a three-necked flask, adding DL-methionine while stirring until the DL-methionine is completely dissolved in the hydrobromic acid. Then, add concentrated sulfuric acid dropwise. After the concentrated sulfuric acid is added, add a tail gas absorption device and react at 130 °C for 12 h. After the reaction is complete, cool to room temperature. Adjust the pH of the reaction solution to 6 with a 10% KOH aqueous solution. Filter, wash the filter cake 2-3 times with distilled water, and dry at 100 °C for 7-8 h to obtain crude DL-homocysteine.

Dissolve DL-homocysteine in HCl solution, then add tin powder and react at 30 °C for 3 h. Then, pass H2S gas through to form SnS precipitate.

Chemical Properties

Acicular crystals.maximum UV absorption 238 nm.

Originator

Citiolase,Roussel Maestretti France,1970

Uses

hepatoprotectant, free radical scavenger

Uses

Photographic antifogging agent: Dersch, US 3068100 (1962); Weber, DE 1164828 (1964 to Adox Fotowerke Schleussner GmbH), C.A. 60, 14050f (1964); protector against radiation: Langendorff, Koch, Strahlentherapie 106, 451 (1958); Braun et al., ibid. 108, 262 (1959), C.A. 52, 18841h (1958); 53, 17325e (1959).

Definition

ChEBI: N-(2-oxo-3-thiolanyl)acetamide is a N-acyl-amino acid.

Manufacturing Process

12.73 kg of acetyl methionine are gradually introduced into a brine-cooled
pressure-tight apparatus provided with a stirrer and containing 140 liters of liquid ammonia at -50°C. The amino acid is dissolved after a short time; 6.5 kg of sodium metal are then introduced over a period of from 4 to 5 hours at a temperature of from -40°C to 60°C. Eventually, a persistent blue coloration of the ammoniacal solution indicates the end of the reaction. The ammonia is distilled off and the residue is taken up in 70 liters of methanol. In order to remove ammonia which has been formed from sodium amide, 30 to 40 liters of methanol are distilled off and the residue is made up with methanol to 80 liters. The strongly alkaline solution is neutralized with 22 liters of concentrated aqueous hydrochloric acid. The solution is filtered off from the precipitated sodium chloride and evaporated to dryness in vacuo. The closing of the thiolactone ring takes place as a result of the evaporation of the solution to dryness in the acid pH range and the N-acetyl homocystein originally present is converted into N-acetyl homocystein thiolactone. In order to isolate this compound, the residue is recrystallized from 25% aqueous alcohol.
9 kg of N-acetyl homocystein thiolactone are obtained, this corresponding to a yield of 85% of the theoretical.

Therapeutic Function

Hepatoprotectant

Purification Methods

Dry Citiolone in a vacuum desiccator. It recrystallises from toluene as needles. It is a ninhydrin -ve substance which gives a “slow” nitroprusside test. It has max at 238nm ( 4,400 M-1cm-1); and (nujol) 1789s and 851ms cm. [Benesch & Benesch J Am Chem Soc 78 1597max 1956, cf Laliberté J Chem Soc 2756 1963.]

References

[1] Macromolecules, 2015, vol. 48, # 11, p. 3414 - 3421
[2] Science China Chemistry, 2015, vol. 58, # 11, p. 1734 - 1740
[3] Chemical Communications, 2013, vol. 49, # 54, p. 6057 - 6059