Synthesis
In industry, glacial acetic acid and phosphoryl trichloride are usually used, and then the acylation product and phosphorous trichloride hydrolyzate are condensed. Add the metered amount of water and glacial acetic acid into the reaction kettle and stir evenly. Phosphorus trichloride was added dropwise under cooling, and the reaction temperature was controlled at 40-80°C. The reaction by-product hydrogen chloride gas is condensed and sent to the absorption tower to recover hydrochloric acid. The overflowed acetyl chloride and acetic acid were condensed and returned to the reactor. After dropping phosphorus trichloride, the temperature was raised to 100-130°C, and refluxed for 4-5h. After the reaction, hydrolyzed with steam to evaporate the residual acetic acid and low boilers to obtain 1-Hydroxyethylidene-1,1-diphosphonic acid.
Description
Hydroxyethylidene diphosphonic acid (HEDP) is a new type of chlorine-free electroplating complexing agent. It is used as the main agent for stable water quality in the circulating cooling water system, and plays the role of corrosion and scale inhibition. This product is one of the organic polyphosphonic acid-free water tablet conditioners. There are also some other varieties of such products produced in China, such as aminotrimethylenephosphonic acid (ATMP): [CH2PO(OH)2]3N and ethyl acetate Diaminetetramethylenephosphoric acid (EDTMP) and so on. Organic polyphosphonic acid is a type of water treatment agent developed in the late 1960s and confirmed around the 1970s.
Chemical Properties
light beige powder
Originator
Etidron,Gentili,Italy,1977
Uses
1-Hydroxyethylidenebis(phosphonic acid) acts as human protein tyrosine phosphatase inhibitor. It is also useful for photographic applications. It finds application to strengthen bone, osteoporosis treatment and to treat Paget's disease of bone. In addition, it is used in corrosion inhibition in circulating cool water systems, oil fields and low-pressure boilers with electric power, the chemical industry, metallurgy and fertilizers. It is also utilized for formulating reverse osmosis and thermal desalination anti-scaling agents. Furthermore, it is used in detergents, water treatment, cosmetics and pharmaceuticals.
Uses
Etidronate (Didronel) is a human protein tyrosine phosphatase inhibitor with IC50 of 0.2 μM.
Definition
ChEBI: A 1,1-bis(phosphonic acid) that is (ethane-1,1-diyl)bis(phosphonic acid) having a hydroxy substituent at the 1-position. It inhibits the formation, growth, and dissolution of hydroxyapatite crystals by chemisorption to calcium phosphate surfaces.
Manufacturing Process
Phosphorous acid was premixed with acetic acid to form a 50 wt % solution of
phosphorous acid dissolved in acetic acid. The acids were mixed on a molar
basis of 1.36:1, acetic acid to phosphorous acid, and this corresponded on a
mol percentage basis to 57.6% acetic acid and 42.4% phosphorous acid.
Acetic anhydride was continuously metered into a stream of the phosphorous
acid-acetic acid mixture to form the reaction solution. The acetic anhydride
was metered into the acid mixture at a mol ratio of 1.33 mols of acetic
anhydride per mol of phosphorous acid. The metering rates were 18.5 lb/hr of
the phosphorous acid/acetic acid premixed solution and 15.1 lb/hr acetic
anhydride. The reaction solution was continuously passed through a heat
exchanger where it was heated to 190°F then it was continuously fed into a
two stage back-mix reaction zone where due to the heat of reaction the
temperature rose to 275°F. The average residence in the reaction zone was 27
min. The reaction zone consisted of two back-mix reactors each having a
capacity of 7.5 pounds of the reaction solution. A stream of reaction solution
was continuously with drawn from the second reactor and continuously mixed
with a stream of water which was being metered at a rate of 2 lb/hr. This
amount of water corresponded to 18% excess over the theoretical amount
necessary to hydrolyze all of the acetyl-containing compounds in the reaction
solution to free acids. The hydrolyzed solution was continuously passed
through a heat exchanger and cooled to room temperature after which the
solution was continuously passed to a crystallizer where, with agitation, the
ethane-1-hydroxy-1,1-diphosphonic acid crystallized. The slurry was then
filtered and the crystals were recovered and dried. Analysis of the product
showed a conversion rate of phosphorous acid to ethane-1-hydroxy-1,1-
diphosphonic acid of 86%. Sodium hydroxide may be used to give the
disodium salt.
brand name
Didronel (Millot Laboratories, France);
Didronel (Procter & Gamble).
Therapeutic Function
Bone calcium regulator
Flammability and Explosibility
Not classified
in vitro
Etidronic acid (Etidronate) (10 mM, 24 h) shows cytotoxicity, causes a decrease in the S-phase population and an increase in the G2/M population, and induces p53 mutation in MCF-7 cells.
Etidronic acid (100 nM, 24 h) induces osteoclast apoptosis, which displays characteristics of apoptosis, including chromatin condensation and changed cellular and nuclear morphology, detected by fluorescence microscopy.
