MALONIC ACID BIS(2,4,6-TRICHLOROPHENYL) ESTER

MALONIC ACID BIS(2,4,6-TRICHLOROPHENYL) ESTER Property

Melting point:

149-150 °C(Solv: benzene (71-43-2))

Boiling point:

559.6±50.0 °C(Predicted)

Density 

1.648±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

form 

solid

pka

8.02±0.46(Predicted)

color 

off white

InChI

InChI=1S/C15H6Cl6O4/c16-6-1-8(18)14(9(19)2-6)24-12(22)5-13(23)25-15-10(20)3-7(17)4-11(15)21/h1-4H,5H2

InChIKey

WYPCGKBOSFOHGU-UHFFFAOYSA-N

SMILES

C(OC1=C(Cl)C=C(Cl)C=C1Cl)(=O)CC(OC1=C(Cl)C=C(Cl)C=C1Cl)=O

Safety

HazardClass 

IRRITANT

HS Code 

2917198090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

MALONIC ACID BIS(2,4,6-TRICHLOROPHENYL) ESTER Chemical Properties,Usage,Production

Uses

Bis(2,4,6-trichlorophenyl) Malonate can be used as novel orally active inhibitor of HLE to treat chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis and several inflammatory diseases.

Synthesis

The general procedure for the synthesis of bis(2,4,6-trichlorophenyl) malonate from malonic acid and 2,4,6-trichlorophenol was as follows: 2,4,6-trichlorophenol (15.8 g, 80 mmol) and malonic acid (4.1 g, 40 mmol) were added to phosphorus triclosamide (100 mL, 1.05 mol) according to the literature method. The reaction mixture was stirred under reflux conditions for 4 hours until the cessation of the escape of hydrogen chloride gas was confirmed by litmus test. The warm crystalline suspension was slowly poured into ice water (500 g) and stirred continuously for 30 minutes. Off-white crystals were collected by filtration and subsequently transferred to a mixture containing water (100 mL) and saturated aqueous sodium bicarbonate (50 mL). After stirring for 30 min, the crystals were filtered again, washed thoroughly with distilled water (3 x 40 mL) and finally dried under vacuum to afford the target product bis(2,4,6-trichlorophenyl) malonate (18.5 g, 95% yield) as a white fine solid. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.39 (4H, s, Ar-H), 4.05 (2H, s, CH2).

References

[1] European Journal of Medicinal Chemistry, 2003, vol. 38, # 4, p. 421 - 425
[2] Patent: WO2007/16525, 2007, A2. Location in patent: Page/Page column 94; 101-103
[3] Patent: US2008/188467, 2008, A1. Location in patent: Page/Page column 26-27; 29-30; 40-41; 50-51
[4] Patent: US2013/281397, 2013, A1. Location in patent: Paragraph 0450; 0465
[5] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3796 - 3808