Diphenhydramine Hydrochloride CAS NO.147-24-0

Product Name:    Diphenhydramine Hydrochloride
Synonyms:    2-(diphenylmethoxy)-n,n-dimethyl-ethanaminhydrochloride;2-(diphenylmethoxy)-n,n-dimethyl-ethylaminhydrochloride;Actifed;alpha-Hydroxydiphenylmethane-beta-dimethylaminoethyl ether hydrochloride;alpha-hydroxydiphenylmethane-beta-dimethylaminoethyletherhydrochloride;Ambenyl;BAX;Benacine
CAS:    147-24-0
MF:    C17H22ClNO
MW:    291.82
EINECS:    205-687-2
Mol File:    147-24-0.mol                     

Melting point     168-172 °C
Boiling point     163-167 °C(Press: 3 Torr)
density     1.0489 (rough estimate)
refractive index     1.5800 (estimate)
Fp     9℃
storage temp.     2-8°C
solubility     Very soluble in water, freely soluble in alcohol.
form     Crystalline Powder or Adhering Crystals
color     White
PH    pH(100g/L, 25℃) 4.0～5.5
Water Solubility     1000 g/L
Sensitive     Light Sensitive
Merck     14,3309
Stability:    Stable, but slowly darkens upon exposure to light. Incompatible with strong oxidizing agents.
InChIKey    PCHPORCSPXIHLZ-UHFFFAOYSA-N
CAS DataBase Reference    147-24-0(CAS DataBase Reference)
NIST Chemistry Reference    diphenhydramine hydrochloride(147-24-0)
EPA Substance Registry System    Diphenhydramine hydrochloride (147-24-0)
Safety Information
Hazard Codes     Xn,T,F
Risk Statements     22-39/23/24/25-23/24/25-11
Safety Statements     36-45-36/37-16-7-24/25
RIDADR     2811
WGK Germany     3
RTECS     KR7000000
HS Code     29221990
Toxicity    LD50 orally in rats: 500 mg/kg (Gruhzit, Fisken)
MSDS Information
Provider    Language
N-(2-Diphenylmethoxyethyl)-N,N-dimethylamine hydrochloride    English
SigmaAldrich    English
ACROS    English
ALFA    English
Diphenhydramine Hydrochloride Usage And Synthesis
Description    Diphenhydramine hydrochloride is an antihistamine drug having the chemical name 2-(Diphenylmethoxy)- N,N-dimethylethylamine hydrochloride. It occurs as a white, crystalline powder, is freely soluble in water and alcohol and has a molecular weight of 291.82.
The molecular formula is C17H21NO·HCl and the structural formula is as follows:
Diphenhydramine hydrochloride structural formula
Diphenhydramine hydrochloride in the parenteral form is a sterile, pyrogen-free solution available in a concentration of 50 mg of diphenhydramine hydrochloride per mL. The solutions for parenteral use have been adjusted to a pH between 5.0 and 6.0 with either sodium hydroxide or hydrochloric acid and contains 0.1 mg/mL benzethonium chloride as a germicidal agent.
Clinical Pharmacology    Diphenhydramine hydrochloride is an antihistamine with anticholinergic (drying) and sedative side effects. Antihistamines appear to compete with histamine for cell receptor sites on effector cells. Diphenhydramine hydrochloride in the injectable form has a rapid onset of action. Diphenhydramine hydrochloride is widely distributed throughout the body, including the CNS. A portion of the drug is excreted unchanged in the urine, while the rest is metabolized via the liver. Detailed information on the pharmacokinetics of Diphenhydramine Hydrochloride Injection is not available.
Indications and Usage    Diphenhydramine hydrochloride in the injectable form is effective in adults and pediatric patients, other than premature infants and neonates, for the following conditions when diphenhydramine hydrochloride in the oral form is impractical.
antihistaminic: For amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled, and for other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated.
Motion Sickness: For active treatment of motion sickness.
Antiparkinsonism: For use in parkinsonism, when oral therapy is impossible or contraindicated, as follows: parkinsonism in the elderly who are unable to tolerate more potent agents; mild cases of parkinsonism in other age groups, and in other cases of parkinsonism in combination with centrally acting anticholinergic agents.
Drug overdose    Antihistamine overdosage reactions may vary from central nervous system depression to stimulation. Stimulation is particularly likely in pediatric patients. Atropine-like signs and symptoms; dry mouth; fixed, dilated pupils; flushing; and gastrointestinal symptoms may also occur. Stimulants should not be used. Vasopressors may be used to treat hypotension.
Contraindications    
Use in Neonates or Premature Infants: This drug should not be used in neonates or premature infants.
Use in Nursing Mothers: Because of the higher risk of antihistamines for infants generally, and for neonates and prematures in particular, antihistamine therapy is contraindicated in nursing mothers.
Use as a Local Anesthetic: Because of the risk of local necrosis, this drug should not be used as a local anesthetic.
Antihistamines are also contraindicated in the following conditions: Hyper sensitivity to diphenhydramine hydrochloride and other antihistamines of similar chemical structure.
Chemical Properties    White or almost white, crystalline powder.
Originator    Benadryl,Parke Davis,US,1946
Uses    Diphenhydramine hydrochloride is used as an antihistamine and for its antieholinergie (drying) and sedative effects; for allergic conjunctivitis due to foods; for mild, uncomplicated allergic skin manifestations of urticaria and angioedema; for amelioration of allergic reactions to blood or plasma; for dermatographism; in therapy for anaphylaetie reactions adjunctive to epinephrine and other standard measures after the acute manifestations have been controlled; for active and prophylactie treatment of motion sickness; for parkinsonism; an antiemetic; has local anesthetic properties; in preparations for the relief of cough; in the prevention and treatment of radiation sickness, nausea and vomiting; for treatment of allergie cheilitis and stomatitis.
Uses    Diphenhydramine is a H1-histamine receptor antagonist. Diphenhydramine is categorized as an antihistaminic; sedative, hypnotic.
Uses    antihistamine, sedative, treatment of allergic
Uses    A histamine H1-receptor antagonist.
Uses    H1-Histamine receptor antagonist. Antihistaminic; sedative, hypnotic
Definition    ChEBI: The hydrochloride salt of diphenhydramine.
Manufacturing Process    As described in US Patent 2,421,714: (a) benzhydryl 
omide is first prepared as follows: 840 parts by weight of diphenylmethane is heated to 130°C with stirring. In the presence of a 200 watt electric light 6 inches from the flask, 880 parts of 
omine is added slowly. Liberation of H
occurs and addition requires 1 hour and 45 minutes. The temperature is maintained at 130°C for an additional 30 minutes. A fine stream of air is blown in to remove H
and 
2 while the reaction mixture cools. Benzene (180 parts) is added and the solution used immediately in (b) below.
If pure benzhydryl 
omide is desired the above reaction mixture is dissolved in ether, washed with water, sodium carbonate solution and finally with water. The ether is removed, benzene added and distilled off and the benzhydryl 
omide distilled in vacuo. Yield 85%.
(b) 490 parts β-dimethylaminoethanol and 530 parts of anhydrous sodium carbonate are heated to 110°C with stirring. The addition of the benzenebenzhydryl 
omide mixture is then begun. The temperature is raised to 120°- 125°C. As reaction takes place carbon dioxide is evolved, the addition requires1 hours. The mixture is kept at 125°C for 5 hours additional time. After cooling, 3,000 parts of water is added and the mixture stirred until the inorganic salts are dissolved. The mixture is transferred to a large separatory funnel and 1,500 parts of ether added. The ether solution is washed several times with water and then the ether layer extracted with 1 to 4 hydrochloric acid. The acid solution is treated with 30 parts of Darco and 30 parts Filter-Cel and filtered.
The free base is liberated from the acid solution with 20% sodium hydroxide solution and taken up in ether. The ether layer is washed with water, saturated with NaCl and then shaken with solid potassium hydroxide. The ether is removed by distillation, 200 parts of benzene added and distilled off. The residue is distilled in vacuo and the fraction 150°-165°C/2 mm is collected and amounts to 433 parts. The hydrochloride salt is prepared by dissolving the free base in anhydrous ether and slowly adding an alcoholic solution of hydrogen chloride. The solid is recrystallized from absolute alcohol-ether mixture or isopropanol-ether mixture and has a MP of 161-162°C.
Brand name    Benadryl (Parke-Davis).
Therapeutic Function    Antihistaminic
General Description    Diphenhydramine hydrochloride, 2-(diphenylmethoxy)- N,N-dimethylethanamine hydrochloride (Benadryl), is an oily, lipid-soluble free base available as the bitter-tasting hydrochloride salt, which is a stable, white crystalline powder soluble in water (1:1), alcohol (1:2) and chloroform (1:2). The salt has a pKa value of 9, and a 1% aqueous solution has a pH of about 5. 
In addition to antihistaminic action, diphenhydramine exhibits antidyskinetic, antiemetic, antitussive and antimuscarinic, and sedative properties.As an antihistaminic agent, diphenhydramine is recommended in various allergic conditions and, to a lesser as an antitussive and Parkinsonism drug. It is also used in OTC sleep-aid products. It is administered either orally or parenterally in the treatment of urticaria, seasonal rhinitis (hay fever), and some dermatoses.
General Description    White or almost-white crystalline powder. Odorless with a bitter numbing taste. pH (5% aqueous solution) 4-6.
Air & Water Reactions    Water soluble. Aqueous solutions are acidic.
Reactivity Profile    N-(2-Diphenylmethoxyethyl)-N,N-dimethylamine hydrochloride gives acidic solutions in water. Neutralizes bases. May react with strong oxidizing and strong reducing agents. May catalyze organic reactions. Slowly darkens on exposure to light.
Fire Hazard    Flash point data for N-(2-Diphenylmethoxyethyl)-N,N-dimethylamine hydrochloride are not available; however, N-(2-Diphenylmethoxyethyl)-N,N-dimethylamine hydrochloride is probably combustible.
Biological Activity    H 1 receptor antagonist. Antihistamine.
Contact allergens    This antihistaminic drug with sedative properties is mainly sold over the counter. It can be used both topically (treatment of pruritis) and orally for its antiallergic, antiemetic, sedative, and anticough properties. Allergic or photoallergic contact dermatitis and fixeddrug eruption seem to be rare.
Safety Profile    Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. Human systemic effects by ingestion or skin contact: arrhythmias, ataxia, blood pressure elevation, convulsions, distorted perceptions, eye effects, and hallucinations. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits very toxic fumes of NO, and HCl. See also ESTERS and ETHERS.
Veterinary Drugs and Treatments    In veterinary medicine, diphenhydramine is used principally for its antihistaminic effects, but also for other pharmacologic actions. Its sedative effects can be of benefit in treating the agitation (pruritus, etc.) associated with allergic responses. It has also been used for treatment and prevention of motion sickness and as an antiemetic in small animals. It has been suggested for use as adjunctive treatment of aseptic laminitis in cattle and it may be useful as an adjunctive treatment for feline pancreatitis. For other suggested uses, refer to the Dosage section below.
Diphenhydramine Hydrochloride Preparation Products And Raw materials
Raw materials    Sodium carbonate-->Diphenylmethane