3-Chloro-4-morpholino-1,2,5-thiadiazole Chemical Properties

Melting point:

44-47 °C (lit.)

Boiling point:

307.8±42.0 °C(Predicted)

Density 

1.462±0.06 g/cm3(Predicted)

Flash point:

>230 °F

storage temp. 

2-8°C

solubility 

Chloroform (Sparingly), DMSO (Slightly), Methanol (Slightly)

pka

-0.18±0.10(Predicted)

form 

Solid

color 

White to Off-White

InChIKey

LAUCCQWGVCJGFT-UHFFFAOYSA-N

CAS DataBase Reference

30165-96-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Safety Statements 

22-24/25

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

2934990002

MSDS

• Language:English Provider:SigmaAldrich

3-Chloro-4-morpholino-1,2,5-thiadiazole Usage And Synthesis

Chemical Properties

Brown Solid

Uses

3-Chloro-4-morpholino-1,2,5-thiadiazole (Timolol EP Impurity F; Timolol BP Impurity F; Timolol USP Related Compound F) is an intermediate for the synthesis of Timolol.

Synthesis

The general procedure for the synthesis of 3-chloro-4-morpholino-1,2,5-thiadiazole from morpholine and 3,4-dichloro-1,2,5-thiadiazole was as follows: morpholine (6.75 g, 77.4 mmol) was added to a 100-mL three-necked flask assembled with a reflux condenser tube. The flask was heated to 110 °C and 3,4-dichloro-1,2,5-thiadiazole (3.0 g, 19.3 mmol) was slowly added dropwise over 20 min. After the dropwise addition was completed, the reaction temperature was kept at 110°C with stirring for 2 hours. After completion of the reaction, the reaction mixture was cooled to 0°C in an ice bath. Water (30 mL) was added and the mixture was acidified with concentrated hydrochloric acid. The mixture was stirred at 0 °C until a precipitate precipitated. The solid product was collected by filtration, washed with water and dried. The resulting orange solid was recrystallized by methanol and dried under high vacuum to give 3.5 g (87.9% yield) of 4-(4-chloro-1,2,5-thiadiazol-3-yl)morpholine. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 3.45-3.55 (m, 2H), 3.80-3.90 (m, 2H). Mass spectral analysis showed (M + H)+ = 206.1.

References

[1] Synthesis, 2004, # 10, p. 1625 - 1628
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 14, p. 5281 - 5289
[3] ChemMedChem, 2015, vol. 10, # 2, p. 253 - 265
[4] Angewandte Chemie - International Edition, 2014, vol. 53, # 26, p. 6641 - 6644
[5] Angew. Chem., 2014, p. 6759 - 6762,4

3-Chloro-4-morpholino-1,2,5-thiadiazole(30165-96-9)Related Product Information

• Moroxydine hydrochloride
• Dimethomorph
• Tridemorph
• Moroxydine
• Epichlorohydrin
• 2,1,3-Benzothiadiazole
• 2-Mercapto-5-methyl-1,3,4-thiadiazole
• TiMolol IMpurity E
• Timolol EP Impurity G
• Timolol
• Chloroacetic acid
• morpholine
• Difluorochloromethane
• 3-Chloro-4-morpholino-1,2,5-thiadiazole