- Clenbuterol hydrochloride, NAB-365, Siropent
Clenbuterol, marketed as Dilaterol, Spiropent, Ventipulmin, is a sympathomimetic amine used by sufferers of breathing disorders as a decongestant and bronchodilator. People with chronic breathing disorders such as asthma use this as a bronchodilator to make breathing easier. It is most commonly available as the hydrochloride salt, clenbuterol hydrochloride.
Effects and dosage
Clenbuterol is a β2 agonist with some structural and pharmacological similarities to epinephrine and salbutamol, but its effects are more potent and longer-lasting as a stimulant and thermogenic drug. It causes an increase in aerobic capacity, central nervous system stimulation, blood pressure, and oxygen transportation. It increases the rate at which body fat is metabolized while increasing the body’s basal metabolic rate (BMR). It is commonly used for smooth muscle-relaxant properties as a bronchodilator and tocolytic.
Clenbuterol is also prescribed for treatment of horses, but equine use is usually the liquid form.
Clenbuterol is approved for use in some countries, free or via prescription, as a bronchodilator for asthma patients.
Clenbuterol is not an ingredient of any therapeutic drug approved by the US Food and Drug Administration and is now banned forIOC-tested athletes. In the US, administration of clenbuterol to any animal that could be used as food for human consumption is banned by the FDA.
Clenbuterol is a therapeutic drug for asthma and COPD, approved for human use in some countries in Europe (Bulgaria and Russia) and Asia (China).
Although often used by bodybuilders during their “cutting” cycles, the drug has been more recently known to the mainstream, particularly through publicized stories of use by celebrities such as Victoria Beckham, Britney Spears, and Lindsay Lohan,  for its off-label use as a weight-loss drug similar to usage of other sympathomimetic amines such as ephedrine, despite the lack of sufficient clinical testing either supporting or negating such use.
By bromination of 4-amino-3,5-dichloroacetophenone (I) with Br2 in CHCl3 to give 4-amino-3,5-dichloro-alpha-bromoacetophenone (II), m.p. 140-5 C, which is condensed with tert-butylamine (III) in CHCl3 to 4-amino-3,5-dichloro-alpha-tertbutylaminoacetophenone hydrochloride (IV), m.p. 252-7 C; this product is finally reduced with NaBH4 in methanol.
Synthesen von neuen Amino-Halogen-substituierten Phenyl-aminothanolen. Arzneim-Forsch Drug Res 1972, 22, 5, 861-869
Synthesis and Characterization of Bromoclenbuterol
Ravi Kumar Kannasani*, Srinivasa Reddy Battula, Suresh Babu Sannithi, Sreenu Mula and Venkata Babu VV
R&D Division, RA Chem Pharma Limited, API, Hyderabad, Telangana, India
- *Corresponding Author:
- Ravi Kumar Kannasani
R&D Division, RA Chem Pharma Limited
API, Prasanth Nagar, Hyderabad, Telangana, India
Citation: Kannasani RK, Battula SR, Sannithi SB, Mula S, Babu VVV (2016) Synthesis and Characterization of Bromoclenbuterol. Med Chem (Los Angeles) 6:546-549. doi:10.4172/2161-0444.1000397
Clenbuterol, it is most commonly available as the hydrochloride salt, clenbuterol hydrochloride. Clenbuterol, marketed as Dilaterol, Spiropent, Ventipulmin, and also generically as clenbuterol, is a sympathomimetic amine used for breathing disorders as a decongestant and bronchodilator. People with chronic breathing disorders such as asthma use this as a bronchodilator to make breathing easier. Clenbuterol is a β2 agonist with some structural and pharmacological similarities to epinephrine and salbutamol, but its effects are more potent and longerlasting as a stimulant and thermogenic drug. It causes an increase in aerobic capacity, central nervous system stimulation, blood pressure, and oxygen transportation. It increases the rate at which body fat is metabolized while increasing the body’s BMR. It is commonly used for smooth muscle-relaxant properties as a bronchodilator and tocolytic. Clenbuterol is also prescribed for treatment of horses, but equine use is usually the liquid form
Clenbuterol Hydrochloride was first synthesized at Thomae; a Boehringer Ingelheim research facility in Biberach, Germany, in 1967. The synthesis of Clenbuterol Hydrochloride was patented in the United States in 1970. After comprehensive clinical trials, Clenbuterol Hydrochloride was approved for the treatment of reversible airway obstruction in Germany in 1976 and later as a veterinary pharmaceutical for the treatment of bronchiolytic disorders in Germany in 1980. Boehringer Ingelheim markets Clenbuterol Hydrochloride as Spirospent for Human Pharmaceuticals and as Ventipulmin for Veterinary Pharmaceuticals. Clenbuterol Hydrochloride is not approved by the Federal Drug Administration for human use in the United States.
As per the available literature [4–7], clenbuterol hydrochloride was synthesized from 4-amino acetophenone (Scheme 1). Initially 4-amino acetophenone (1) was reacted with chlorine to afford 4-amino-3,5- dichloro acetopheneone (2) which was further reacted bromine to give 1-(4-amino-3,5-dichlorophenyl)-2-bromoethanone (3). The obtained bromo compound was reacted tertiary butyl amine to afford 2-(tertbutylamino)- 1-(4-amino-3,5-dichlorophenyl)ethanone (4), which was further reduced with sodium borohydride to give clenbuterol base (5) and converted in to hydrochloride salt by using alcoholic HCl to get clenbuterol hydrochloride (6).
In the synthesis of clenbuterol hydrochloride, first step was a double chlorination of 4-aminoacetophenone (1) through an electrophillic aromatic substitution reaction to yield 4-amino-3,5- dichloroacetophenone (2). Due to the ortho/para directing, amino group and the meta directing, electron withdrawing, acetyl group, chlorination of 4-aminoacetophenone occurs primarily at the 3 and 5 positions over the 2 and 6 positions. Therefore, under chlorination would produce only the mono chlorinated impurity, 4-amino-3- chloroacetophenone. Under these conditions, over chlorination does not result in the addition of chlorine to the 2 and 6 positions because the amino and acetyl groups do not direct that addition. Even though chlorides are ortho/para directing and direct to the 2 and 6 position, chlorides are also deactivating. After close observation on this chlorination reaction, it was noted that the formed mono chlorinated impurity (Scheme 2) (4-amino-3-chloro acetophenone) caused the formation of process related impurity (bromoclenbuterol) in clenbuerol synthesis.
References for above
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and (R)-(−)-clenbuterol (bottom)
|Systematic (IUPAC) name|
|AHFS/Drugs.com||International Drug Names|
|Oral (tablets, oral solution)|
|Biological half-life||36–48 hours|
|Excretion||Feces and urine|
|ATC code||R03AC14 (WHO)R03CC13 (WHO)QG02CA91 (WHO)|