Bupropion Chemical Properties

Melting point:

233-234°C

Boiling point:

bp.005 52°

Density 

1.066±0.06 g/cm3(Predicted)

solubility 

ethanol: 193 mg/mL solutions may be stored for several days at 4 °C.

form 

solid

pka

pKa 7.0 (Uncertain)

color 

white

BCS Class

1

CAS DataBase Reference

34911-55-2(CAS DataBase Reference)

EPA Substance Registry System

1-Propanone, 1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]- (34911-55-2)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

Safety Statements 

36

WGK Germany 

3

RTECS 

UG8858000

HazardClass 

IRRITANT

Hazardous Substances Data

34911-55-2(Hazardous Substances Data)

MSDS

• Language:English Provider:SigmaAldrich

Bupropion Usage And Synthesis

Description

Bupropion hydrochloride, an aminoketone structurally unrelated to tricyclics or tetracyclics, is a dopamine uptake blocker with antidepressant activity. Its clinical efficacy is reportedly comparable to that of amitriptyline, yet unlike most conventional antidepressants, bupropion hydrochloride is not associated with orthostatic hypotension or other cardiovascular side-effects.

Originator

Burroughs Wellcome (United Kingdom)

Uses

vasoconstrictor;non-selective agonist of all adrenergic receptors

Uses

Bupropion Hydrochloride used in methods of treating sleep disorders associated with pain.

Definition

ChEBI: Bupropion is an aromatic ketone that is propiophenone carrying a tert-butylamino group at position 2 and a chloro substituent at position 3 on the phenyl ring. It has a role as an antidepressant, an environmental contaminant and a xenobiotic. It is a secondary amino compound, a member of monochlorobenzenes and an aromatic ketone.

Manufacturing Process

To ethyl magnesium bromide (2 L, 3 M) was added over 45 min with stirring and cooling m-chlorobenzonitrile (688.0 g, 5 mole) in ether (2.5 L). The resultant solution was heated under gentle reflux for 5 h. The reaction mixture was hydrolyzed with cold dilute hydrochloric acid, the ether was distilled off, and the aqueous solution was heated at 90°C for 1 h. The flask was then cooled. The solid ketone that separated was washed with cold water and recrystallized from methanol. The recrystallized m-chloropropiophenone, melting point 39°-40°C, weighed 750.0 g.
In methylene chloride (3 L) was dissolved m-chloropropiophenone (698.0 g; 4.15 mole). The solution was stirred with charcoal (Darco) and magnesium sulfate for 2 h and filtered. To it was added with stirring (662.0 g) of bromine in methylene chloride (1 L). When the bromine color had faded completely, the solvent was evaporated in vacuum and m-chloro-α-bromopropiophenone was obtained as oil.
The m-chloro-α-bromopropiophenone was dissolved in acetonitrile (1300 ml). To this, t-butylamine (733.0 g) in acetonitrile (1300 ml) was added while keeping the temperature below 32°C. The reaction mixture was allowed to stand over night. It was then partitioned between water (4200 ml) and ether (2700 ml). The aqueous layer was extracted with a further portion of ether (1300 ml). The combined ethereal layers were then washed with water (4200 ml) to which hydrochloric acid was added until the pH of the aqueous layer was 9. The aqueous layer was separated and washed with ether (500 ml) and then discarded. The combined ethereal layers were then stirred with ice (560.0 g) and concentrated hydrochloric acid (324 ml). The ethereal layer was separated and again washed with water (200 ml) and concentrated hydrochloric acid (50 ml). These last two acid layers were combined and concentrated in vacuum until crystals appeared. The solution was then chilled to 5°C and filtered. The product was sucked dry, washed with acetone and recrystallized from a mixture of isopropanol (3 L) and absolute ethanol (800 ml). The DL-m-chloro-α-t-butylaminopropiophenone hydrochloride so was obtained, melting point 233°-234°C.
The DL-m-chloro-α-t-butylaminopropiophenone was obtained by treatment of DL-m-chloro-α-t-butylaminopropiophenone hydrochloride with sodium hydroxide.

brand name

Wellbutrin (GlaxoSmithKline); Zyban (GlaxoSmithKline).

Therapeutic Function

Antidepressant; Smoking cessation aid

Biological Functions

Bupropion (Wellbutrin) is a pharmacologically unique antidepressant, since it is a weak inhibitor of both dopamine and norepinephrine neuronal reuptake. However, its actual antidepressant activity is not well understood. Bupropion is generally well tolerated and does not block muscarinic, histaminergic, or adrenergic receptors. Unlike the SSRIs and venlafaxine, bupropion does not cause sexual side effects. However, it can cause CNS stimulation, including restlessness and insomnia. High doses of bupropion, given as its original formulation, were associated with a risk of seizures in 0.4% of patients. However, this risk is lower with slow-release bupropion (Wellbutrin SR). This formulation still requires dosing twice a day, and bupropion is contraindicated in patients with a history of seizures. Bupropion inhibits the cytochrome P450 2D6 isoenzyme and may elevate blood levels of drugs metabolized by this route.

General Description

The mechanism of action of bupropion (Wellbutrin) is consideredcomplex and reportedly involves a block of DA reuptakevia the dopamine transporter (DAT), but the overallantidepressant action is noradrenergic. A metabolite thatcontributes to the overall action and its formation can beeasily rationalized. Oxidation of one of the methyl groupson the t-butyl substituent yields hydroxybupropion, an activemetabolite. Reduction of the keto group also occurs,yielding threohydrobupropion and erythrohydrobupropion.Both of these metabolites are also active.
Hydroxybupropion is half as potent as the parent bupropion,and the hydrobupropion isomers are five times less potent.The presence of these metabolites, especially hydroxybupropionwhich is formed by cytochrome P450 2D6(CYP2D6), suggests that there will be a myriad of drug interactionswith bupropion.

Pharmacology

Bupropion is an α-aminoketone that is structurally related to amphetamines, and it exhibits unique activity comparable to that of other antidepressants. It is believed that bupropion restores the total amount of norepinephrine in the body. This compound is a poor reuptake inhibitor of dopamine, and does not exhibit anticholinergic activity or inhibit MAO. Its efficacy as an antidepressant is comparable to that of tricyclic antidepressants, and as a serotonin uptake inhibitor it is comparable to fluoxetine.

Synthesis

The synthesis of bupropion, 1-3(-chlorophenyl)-2-[(1,1-dimethylethyl)amino]- 1-propanone (7.3.5), begins with the reaction of 3-chlorobenzonitrile, with ethylmagnesium bromide to give 3-chloropropiophenone (7.3.3). Brominating this with bromine gives 3-chloro-|á-bromopropiophenone (7.3.4), which on reaction with tert-butylamine gives bupropion (7.3.5) [54¨C58].

Bupropion(34911-55-2)Related Product Information

• 4-Methoxyphenylacetone
• Glycine
• tert-Butanol
• Citric acid monohydrate
• ALTRENOGEST
• Tris(hydroxymethyl)aminomethane
• Propane
• 6-Aminocaproic acid
• BUPROPION HYDROCHLORIDE,BUPROPION HYDROCHLORIDE SELECTIVE DOPAMI NE UP,BUPROPION HYDROCLORIDE,BUPROPION HCL
• Propiophenone
• Phenylacetone
• Amphenidone
• Hydroxybupropione
• Bupropion metabolite B
• Bupropion metabolite A
• Amfepramone hydrochloride
• Bupropion metabolite C
• DIETHYLPROPION