Diphenhydramine CAS 58-73-1
Introduction：Basic information about Diphenhydramine CAS 58-73-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Diphenhydramine Basic information
| Product Name: | Diphenhydramine |
| Synonyms: | Syntedril;Syntodril;Vena;n,n-dimethyl-4,4-diphenyl-3-oxabutylamine;AURORA KA-7664;DIPHENHYDRAMINE;DIPHENHYDRAMINE BASE;Diphenyldramine |
| CAS: | 58-73-1 |
| MF: | C17H21NO |
| MW: | 255.35 |
| EINECS: | 200-396-7 |
| Product Categories: | chemical research;medicine grade;pharmaceutical intermediate |
| Mol File: | 58-73-1.mol |
Diphenhydramine Chemical Properties
| Melting point | 167-172°C |
| Boiling point | bp2.0 150-165° |
| density | 0.9889 (rough estimate) |
| refractive index | 1.5450 to 1.5490 |
| storage temp. | Keep in dark place,Inert atmosphere,Room temperature |
| solubility | Chloroform (Slightly), Methanol (Slightly) |
| pka | pKa 9.1 (Uncertain) |
| form | Oil |
| color | Oil |
| Merck | 14,3309 |
| BCS Class | 1 |
| InChI | InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3 |
| InChIKey | ZZVUWRFHKOJYTH-UHFFFAOYSA-N |
| SMILES | C(N(C)C)COC(C1=CC=CC=C1)C1=CC=CC=C1 |
| CAS DataBase Reference | 58-73-1(CAS DataBase Reference) |
| NIST Chemistry Reference | Ethylamine, 2-diphenylmethoxy-n,n-dimethyl-(58-73-1) |
| EPA Substance Registry System | Ethanamine, 2-(diphenylmethoxy)-N,N-dimethyl- (58-73-1) |
Safety Information
| RTECS | KR6825000 |
| TSCA | TSCA listed |
| HS Code | 2922.19.7000 |
| Hazardous Substances Data | 58-73-1(Hazardous Substances Data) |
| Toxicity | LD50 oral in rat: 390mg/kg |
| Description | Diphenhydramine is one of the main representatives of antihistamine drugs that block H1receptors. Besides antihistamine activity, diphenhydramine exhibits a local anestheticeffect, relaxes smooth muscle, and has sedative and soporific action. |
| Originator | Benadryl,Parke Davis,US,1946 |
| Uses | Diphenhydramine also reduces muscle rigidity and general stiffness, and has a relativelyminor effect on tremors. |
| Uses | Diphenhydramine is used for symptoms of allergies, for treating hives, hay fever, serumsickness, and other allergic illnesses, and also as a sedative and soporific drug as an independentas well as in combination with other drugs. Synonyms of this drug are dimedrol,benadryl, allergina, valdren, and many others. |
| Uses | Antihistaminic. |
| Definition | ChEBI: Diphenhydramine is an ether that is the benzhydryl ether of 2-(dimethylamino)ethanol. It is a H1-receptor antagonist used as a antipruritic and antitussive drug. It has a role as a H1-receptor antagonist, an antiemetic, a sedative, an anti-allergic agent, a muscarinic antagonist, an antiparkinson drug, an antipruritic drug, a local anaesthetic, an antidyskinesia agent, an antitussive and a oneirogen. It is an ether and a tertiary amino compound. |
| Manufacturing Process | As described in US Patent 2,421,714: (a) benzhydryl omide is first preparedas follows: 840 parts by weight of diphenylmethane is heated to 130°C withstirring. 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 additionrequires 1 hour and 45 minutes. The temperature is maintained at 130°C foran 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 thesolution used immediately in (b) below. If pure benzhydryl omide is desired the above reaction mixture is dissolvedin 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 sodiumcarbonate 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. Aftercooling, 3,000 parts of water is added and the mixture stirred until theinorganic salts are dissolved. The mixture is transferred to a large separatoryfunnel and 1,500 parts of ether added. The ether solution is washed severaltimes with water and then the ether layer extracted with 1 to 4 hydrochloricacid. The acid solution is treated with 30 parts of Darco and 30 parts Filter-Celand filtered. The free base is liberated from the acid solution with 20% sodium hydroxidesolution and taken up in ether. The ether layer is washed with water, saturatedwith NaCl and then shaken with solid potassium hydroxide. The ether isremoved by distillation, 200 parts of benzene added and distilled off. Theresidue is distilled in vacuo and the fraction 150°-165°C/2 mm is collectedand amounts to 433 parts. The hydrochloride salt is prepared by dissolvingthe free base in anhydrous ether and slowly adding an alcoholic solution ofhydrogen chloride. The solid is recrystallized from absolute alcohol-ethermixture or isopropanol-ether mixture and has a MP of 161-162°C. |
| Therapeutic Function | Antihistaminic |
| Trade name | Benadryl (Parke-Davis) |
| Contact allergens | This antihistaminic drug with sedative properties ismainly 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 fixeddrugeruption seem to be rare. |
| Safety Profile | Deadly human poisonby an unspecified route. Poison byingestion, intravenous, intraperitoneal, andsubcutaneous routes. Experimentalreproductive effects. Human systemiceffects by ingestion: somnolence, alterationof operant conditioning, changes inpsychophysiological tests. Human mutationdata reported. When heated todecomposition it emits toxic fumes of NO,.See also ETHERS. |
| Synthesis | Diphenhydramine, 2-diphenylmethoxy-N,N-dimethylamine (10.2.5), issynthesized by the esterification of 2-dimethylaminoethanol with benzhydrylbromide [35¨C37]. |
| Environmental Fate | Diphenhydramine is fairly stable in the environmentalthough it does undergo photodegradation. Conjugates ofdiphenhydramine such as diphenhydramine-N-glucuronidemay be converted back to the parent compound, diphenhydramine,through enzymatic cleavage during sewage treatmentprocess. Diphenhydramine is removed poorly through wastewatertreatment processes and is found in significant concentrationsin aquatic organisms downstream from such plants. Diphenhydramine has significant risk for bioaccumulation,particularly in water downstream from wastewater and sewagetreatment facilities. |
| Solubility in water | One gram of diphenhydramine is soluble in 1 mL of water, 2 mL of ethanol, 2 mL of chloroform, or 50 mL of acetone; the compound is very slightly soluble in benzene or ether. |
| Toxicity evaluation | The toxicity of antihistamines is related to their anticholinergic(antimuscarinic), antihistamine, and serotonergic activation.The action of acetylcholine at the muscarinic receptors isblocked, resulting in signs and symptoms of anticholinergicpoisoning. Diphenhydramine may produce direct toxicityunrelated to its anticholinergic properties including inhibitionof cardiac fast sodium channels and at higher concentrations,the drug may inhibit potassium channels, which can result inQT prolongation. Diphenhydramine also blocks the reuptakeof serotonin and has been reported to cause serotoninsyndrome in some individuals during overdose. The action ofdiphenhydramine at H-1 receptors causes sedation. |
Diphenhydramine Preparation Products And Raw materials
| Raw materials | Dimethylamine-->2-Chloroethanol-->Benzyl alcohol-->Diphenylmethane-->Sodium carbonate-->N,N-Dimethyl-2-(benzyloxy)ethanamine-->2-(DIPHENYLMETHOXY)-N-METHYLETHYLAMINE-->Diphenhydramine-->Diphenhydramine Hydrochloride-->Chlorodiphenylmethane-->2-Dimethylaminoethanol-->2-Chloroethyldimethylamine-->Benzhydrol |
| Preparation Products | [2-(diphenylmethoxy)ethyl]trimethylammonium bromide |
