2219-30-9 Usage
Originator
Cuprimine,MSD,US,1963
Uses
D-Penicillamine Hydrochloride showed protective effect on mitochondrial respiration in the brain. It is used in the treatment of Wilson’s disease and heavy metal poisoning. D-Penicillamine Hydrochloride is the salt form of D-Penicillamine (P223000).
Manufacturing Process
(a) Preparation of mercuric chloride complex of penicillamine: To a solution of 372 g (1 mol) of potassium benzyl-penicillin in 940 ml of distilled water at room temperature is added a solution of 40 g (1 mol) of sodium hydroxide in 180 ml of distilled water over a period of one-half hour. The solution is then stirred for two hours at room temperature. While maintaining room temperature, 67 ml of concentrated hydrochloric acid is added at a slow rate. This solution is then added, over a period of time of one-half hour, to a solution of 271 g (1 mol) of HgCl2 in 3.52 liters of distilled water in the presence of 50 g of Hyflo and 5 ml of octyl alcohol. After one hour of agitation, the resulting mixture is treated with 185 ml of concentrated hydrochloric acid and filtered.
(b) Removal of benzylpenilloaldehyde: To the filtrate obtained in step (a), warmed to 50°C is slowly added 108 g (1 mol) of phenyl hydrazine. The mixture is cooled to room temperature and 84 ml of concentrated hydrochloric acid are added. The mixture is agitated briefly and the precipitated benzylpenilloaldehyde phenyl hydrazone is filtered off.
(c) Preparation of isopropylidene penicillamine hydrochloride: To the filtrate obtained in step (b) is added at 20°C to 25°C a total of 85 g of hydrogen sulfide. The precipitated HgS is filtered off and the filtrate is concentrated under reduced pressure to a volume of 200 to 500 ml. Following a polish filtration, the product-rich concentrate is mixed with 1.5 liters of isobutyl acetate. The mixture is refluxed at about 40°C under reduced pressure in equipment fitted with a water separation device. When no further water separates, the batch is cooled to 30°C and filtered. The reactor is washed with 1 liter of acetone, which is used also to wash the cake. The cake is further washed with 200 ml of acetone. The acetone washes are added to the isobutyl acetate filtrate and the mixture is refluxed for 20 to 30 minutes. After a holding period of one hour at 5°C. the crystals of isopropylidene penicillamine hydrochloride are filtered and washed with 200 ml of acetone. On drying for twelve hours at 25°C this product, containing 1 mol of water, weighs about 178 g (73%).
(d) Preparation of penicillamine hydrochloride: The 178 g of isopropylidene penicillamine hydrochloride obtained in step (c) is dissolved in 350 ml of distilled water. The solution is heated at 90°C to 95°C for one to one and onehalf hours, removing acetone by distillation through an efficient column. There is then added 2.6 liters of isobutyl acetate. The mixture is refluxed at a temperature of about 40°C under reduced pressure in equipment fitted with a water separation device. When no further water separates, the pressure is adjusted so that the mixture distills at a vapor temperature of 83°C to 88°C. A total of 650 ml of distillate is collected. The batch is allowed to cool to 50°C and then filtered. The crystals are washed with isobutyl acetate and then dried at 35°C for 24 hours. The virtually anhydrous penicillamine hydrochloride obtained weighs about 128 g (69% from potassium benzyl-penicillin).
Therapeutic Function
Antiarthritic
Safety Profile
A poison by intraperitoneal route. Moderately toxic by ingestion and intravenous routes. Human systemic effects by ingestion: dermatitis. When heated to decomposition it emits very toxic fumes of NOx, SOx, and HCl.
Check Digit Verification of cas no
The CAS Registry Mumber 2219-30-9 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,2,1 and 9 respectively; the second part has 2 digits, 3 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 2219-30:
(6*2)+(5*2)+(4*1)+(3*9)+(2*3)+(1*0)=59
59 % 10 = 9
So 2219-30-9 is a valid CAS Registry Number.
InChI:InChI=1/C5H11NO2S.ClH/c1-5(2,9)3(6)4(7)8;/h3,9H,6H2,1-2H3,(H,7,8);1H/t3-;/m0./s1
2219-30-9Relevant articles and documents
(2R,4S)-2-aminomethyl-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid dihydrochloride: Synthesis, epimerization, and derivatives
Imming
, p. 81 - 86 (2007/10/02)
The preparation of the title compound 6a from penicillamine 5 or from penicillins 7, the spectroscopic data and stereochemical assignments are given. 6a quickly epimerizes at C-2 in dilute aqueous solution. Details are given along with the preparation of the new thiazolidines 10-13 from 6.
Method for preparing d-penicillamine and salts thereof
-
, (2008/06/13)
D-Penicillamine and salts thereof may be prepared by reacting certain aryl amines with 4-thiazolidinecarboxylic acid compounds obtained by splitting the β-lactam ring of penicillin derivatives such as benzylpenicillin or phenoxymethylpenicillin.
Optically active salt of protected D-penicillamine and L-lysine
-
, (2008/06/13)
D,L-penicillamine is converted to D-penicillamine with the aid of L-lysine.
