Ephedrine Chemical Properties

Melting point:

37-39 °C(lit.)

alpha 

-41 º (c=5, 1M HCl)

Boiling point:

255 °C(lit.)

Density 

1.124 g/mL at 25 °C(lit.)

refractive index 

1.4820 (estimate)

Flash point:

186 °F

storage temp. 

Refrigerator (+4°C)

solubility 

Water (easy), ethanol (easy), ether (easy)

pka

pKa 8.02 (Uncertain);9.5 (Uncertain)

optical activity

[α]21/D 41°, c = 5 in 1 M HCl

Water Solubility 

47.62g/L(25 ºC)

Merck 

13,3639

BRN 

2208730

Stability:

Stable. Combustible. Incompatible with strong acids, acid chlorides, acid anhydrides, strong oxidizing agents. May discolour in light.

CAS DataBase Reference

299-42-3(CAS DataBase Reference)

NIST Chemistry Reference

Ephedrine(299-42-3)

EPA Substance Registry System

Ephedrine (299-42-3)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

Safety Statements 

22-25

WGK Germany 

1

RTECS 

KB0700000

F 

3-10

Hazard Note 

Harmful

HS Code 

29394100

Hazardous Substances Data

299-42-3(Hazardous Substances Data)

Toxicity

LD50 oral in rat: 600mg/kg

MSDS

• Language:English Provider:(1R,2S)-(-)-Ephedrine
• Language:English Provider:SigmaAldrich

Ephedrine Usage And Synthesis

Description

Ephedrine is a naturally occurring alkaloid drug (→Alkaloids) derived from Ephedra equistina and Ephedra vulgaris. It can be prepared synthetically. It is used mainly in combination with other agents.

Chemical Properties

white crystals or powder

Originator

CAM,Rybar-UK

Uses

Ephedrine, 1-phenyl-2-methylaminopropanol, C6H5 CH(OH)CH(NHCH3)CH3, is a white-to-colorless granular substance, unctuous (greasy) to the touch, and hygroscopic. The compound gradually decomposes upon exposure to light. Soluble in water, alcohol, ether, chloroform, and oils, and decomposes above this temperature. Ephedrine is isolated from stems or leaves of Ephedra, especially Ma huang (found in China and India). Medically, it is usually offered as the hydrochloride. In the treatment of bronchial asthma, ephedrine is known as a beta agonist. Compounds of this type reduce obstruction by activating the enzyme adenylate cyclase. This increases intracellular concentrations of cAMP (cyclic 3 5 -adenosine monophosphate) in bronchial smooth muscle and mast cells. Ephedrine is most useful for the treatment of mild asthma. In severe asthma, ephedrine rarely maintains completely normal airway dynamics over long periods. Ephedrine also has been used in the treatment of cerebral transient ischemic attacks, particularly with patients with vertabrobasilar artery insufficiency who have symptoms associated with relatively low blood pressure, or with postural changes in blood pressure. Ephedrine sulfate also has been used in drug therapy in connection with urticaria (hives).

Uses

Medicine (bronchodilator).

Definition

ChEBI: A phenethylamine alkaloid that is 2-phenylethanamine substituted by a methyl group at the amino nitrogen and a methyl and a hydroxy group at position 2 and 1 respectively.

Definition

ephedrine: An alkaloid,C₆H₅CH(OH)CH(CH₃)NHCH₃ found inplants of the genus Ephedra, onceused as a bronchodilator in the treatmentof asthma. It is also used as astimulant and appetite suppressant.Structurally, it is a phenylethylamineand is similar to amphetamines, althoughless active. It is, however,widely used in the illegal synthesis ofmethamphetamine. The moleculehas two chiral centres. If the stereo- chemical conformations are opposite(i.e. 1R,2S or 1S,1R) the nameephedrine is used. If the conformationsare the same (1R,2R or 1S,2S)then the compound is called pseudoephedrine.

Manufacturing Process

120 grams of the fermentation product containing phenylpropanolone obtained by extraction with ether (Biochemische Zeit-schrift Vol. 115, 1921, page 282 et seq.) are allowed to run, without further purification, in for about two hours into a solution of 10 g of methylamine in 500 ml of ether in presence of 20 g of activated aluminum, for example of the type described in British Patent No.
336,412, whilst stirring. Simultaneously 20-30 g of water are added, dropwise. At once the vigorous reaction begins. It is moderated by periodical cooling. Activated aluminum is aluminum, which has been amalgamated with mercury. When it contacts with water, it liberates hydrogen and an insoluble aluminum hydroxide is formed. Activated aluminum thus serves as the source of hydrogen for the reaction. When the reaction is complete the ethereal solution is filtered and the optically active base, which formed is extracted from the filtrate by means of dilute acid. There is obtained the hydrochloride of L-1-phenyl-2-methylamino-propanol-1 having a melting point of 214°C, and having the optical rotation given in the literature. The yield amounts to 25-45 g of the hydrochloride depending upon the nature of the parent material.
360 g of ether extract phenylpropanolone used above as parent material are distilled under reduced pressure. 300 grams of the fraction, which distils at 100-150°C/14 mm Hg are subjected to catalytic hydrogenation in presence of colloidal platinum (70 ml of a 1% solution) and 85 grams of a 33% solution of methylamine. It is advantageous to add some ether to the reaction mixture. When absorption of hydrogen is complete, the ethereal solution is shaken with hydrochloric acid and the L-phenyl-2-methylamino-propanol-1 is isolated from the hydrochloric acid extract. The yield of the hydrochloride amounts to 110 grams. MP: 214°C.
100 g of L-1-phenylpropanol-1-one-2 isolated by the method of Neuberg (Biochemische Zeitschrift Vol. 128, 1922, page 611) are dissolved in 200 ml of ether, 75 g of a solution of methylamine (33%) are added and the whole is shaken for about half an hour; condensation occurs with evolution of heat. The reaction mixture is then treated with hydrogen in presence of 70 ml of a 1% colloidal solution of platinum. The reduction product was isolated as hydrochloride. The hydrochloride of L-phenyl-2-methyl-amino-propanol-1 crystallizes from alcohol in the form of coarse prisms. MP: 214°-216°C. The free base melts at 40°C.

brand name

Isofedrol (Boehringer Mannheim GmbH, Germany).

Therapeutic Function

Sympathomimetic; Bronchodilator

Biological Functions

Ephedrine is a naturally occurring alkaloid that can cross the blood-brain barrier and thus exert a strong CNS-stimulating effect in addition to its peripheral actions.The latter effects are primarily due to its indirect actions and depend largely on the release of norepinephrine. However, ephedrine may cause some direct receptor stimulation, particularly in its bronchodilating effects. Because it resists metabolism by both COMT and MAO, its duration of action is longer than that of norepinephrine. As is the case with all indirectly acting adrenomimetic amines, ephedrine is much less potent than norepinephrine; in addition, tachyphylaxis develops to its peripheral actions. Unlike epinephrine or norepinephrine, however, ephedrine is effective when administered orally.

Hazard

Toxic by ingestion.

Mechanism of action

Ephedrine is a naturally occurring sympathomimetic amine that possesses both direct (agonist at α- and β-receptors) and indirect activity via its potentiation of noradrenaline release from sympathetic nerve terminals. It causes an increase in HR, contractility, CO and arterial pressure (systolic > diastolic). Bronchodilation occurs via a β2-mediated mechanism, and it is occasionally used for this purpose. Its duration of action is longer than endogenous catecholamines as it is not metabolised by COMT or MAO. Tachyphylaxis can occur as a result of depletion of noradrenaline from nerve terminals and persistent occupation of adrenergic receptors. Ephedrine crosses the placenta and can increase fetal metabolic rate with a subsequent metabolic acidosis. It is usually administered by i.v. bolus at a dose of 3– 9 mg.

Pharmacology

Ephedrine increases systolic and diastolic blood pressure; heart rate is generally not increased. Contractile force of the heart and cardiac output are both increased. Ephedrine produces bronchial smooth muscle relaxation of prolonged duration when administered orally. Aside from pupillary dilation, ephedrine has little effect on the eye.

Clinical Use

Ephedrine is useful in relieving bronchoconstriction and mucosal congestion associated with bronchial asthma, asthmatic bronchitis, chronic bronchitis, and bronchial spasms. It is often used prophylactically to prevent asthmatic attacks and is used as a nasal decongestant, as a mydriatic, and in certain allergic disorders. Although its bronchodilator action is weaker than that of isoproterenol, its oral effectiveness and prolonged duration of action make it valuable in the treatment of these conditions. Because of their oral effectiveness and greater bronchiolar selectivity, terbutaline and albuterol are replacing ephedrine for bronchodilation.

Side effects

Symptoms of overdose are related primarily to cardiac and CNS effects. Tachycardia, premature systoles, insomnia, nervousness, nausea, vomiting, and emotional disturbances may develop. Ephedrine should not be used in patients with cardiac disease, hypertension, or hyperthyroidism.

Safety Profile

A human poison by an unspecified route. An experimental poison by intravenous, subcutaneous, intramuscular, and intraperitoneal routes. Moderately toxic by ingestion and parented routes. Causes rapid pulse, rise in blood pressure, and other actions similar to epinephrine. An experimental teratogen. Used in production of drugs of abuse. Has been known to cause allergic sensitization. When heated to decomposition it emits toxic fumes of NOx.

Purification Methods

Purify (-)-ephedrine by vacuum distillation (dehydrates) and forms waxy crystals or granules, and may pick up 0.5 H2O. The presence of H2O raises its melting point to 40o. [Moore & Taber J Amer Pharm Soc 24 211 1935.] The anhydrous base crystallises from dry ether [Fleming & Saunders J Chem Soc 4150 1955]. It gradually decomposes on exposure to light and is best stored in an inert atmosphere in the dark (preferably at -20o). Its solubility in H2O is 5%, in EtOH it is 1% and it is soluble in CHCl3, Et2O and mineral oils. It has pKa values in H2O of 10.25 (0o) and 8.69 (60o) [Everett & Hyne J Chem Soc 1136 1958, Prelog & H.flinger Helv Chim Acta 33 2021 1950] and pK a 8.84 in 80% aqueous methoxyethanol [Simon Helv Chim Acta 41 1835 1958]. The hydrochloride has m 220o (from EtOH/Et2O) and [] D20 -38.8o (c 2, EtOH). [IR: Chatten & Levi Anal Chem 31 1581 1959.] The anhydrous base crystallises from Et2O [Fleming & Saunders J Chem Soc 4150 1955]. [Beilstein 13 H 373, 13, III 1720, 13 IV 1879.]

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