Pharmaceutical intermediate Bromhexine Hcl CAS 611-75-6

CAS:611-75-6

MF: C3H7NO3

MW:105.09

EINECS:200-274-3

Specification: 99% min Bromhexine Hcl

Sample:Bromhexine Hcl Powder

Packaging:1kg/bag, 25kg/drum

Brand: Henrikang

Appearance:White

Storage: Cool Dry Place

Shelf Life: 2 Years

Test Method: HPLC

Bromhexine Hcl Usage and Synthesis.

Bromhexine hydrochloride is a kind of mucus and sputum dissolving agent, which can directly act on the bronchial glands, prompting the lysosomes of mucus secretion cells to release, making the mucopolysaccharide fibres in the sputum divided and cleaved, so as to make sputum dilute and easy to cough out.

Clinically, it is mainly used in acute and chronic bronchitis, asthma, bronchial dilatation, emphysema, especially for those who have difficulty in coughing up white mucous sputum, and critical emergencies caused by sputum extensive obstruction of small bronchial tubes.

Bromhexine Hydrochloride is available in oral tablets, solution, aerosol, injection, lyophilised powder injection, I.V. solution and other dosage forms.

Uses and functions of Bromhexine Hcl.

Bromhexine Hydrochloride is a new type of mucolytic expectorant synthesised according to the structure of the active ingredient (fenugreek alkaloids) proposed in the medicinal plant Platycodon grandiflorus, which has a strong effect of dissolving mucous phlegm.

It can make the mucopolysaccharide fibres in phlegm differentiate and cleave, and also inhibit the synthesis of mucopolysaccharide, make the content of salivary acid (one of the components of acidic mucopolysaccharide) in phlegm reduce, so as to reduce the viscosity of phlegm, and there is still a nauseating expectorant effect after oral intake, so that the phlegm can be easily coughed up, so as to make the respiratory tract unobstructed.

Clinically used for acute and chronic bronchitis, asthma, bronchial dilatation, emphysema treatment, especially for white sticky phlegm coughing out the difficulties, and due to phlegm widely obstructed small bronchial tubes caused by shortness of breath and other diseases.

Adverse reactions: nausea and stomach discomfort may occur occasionally after taking this product, which may disappear after reducing the dosage or stopping the drug. A small number of patients with temporary elevation of serum aminotransferases. It should be used with caution in patients with gastric ulcer. The toxicity of this product is very small.

Preparation of Bromhexine Hcl.

Dissolve 2.0g 2-amino-3,5-dibromobenzaldehyde, 1.2g N-methylcyclohexylamine in 20ml methanol, 4g tetraisopropyl titanate was slowly dripped into the reaction solution under the condition of stirring at room temperature, and the reaction was continued to be stirred at room temperature for 5h after the addition; 0.3g of sodium borohydride was added to the reaction solution in batches, and the reaction was stirred at room temperature for 2h. The reaction was completely detected by TLC.

At the end of the reaction, 20 ml of water was added to the reaction solution to quench the reaction, and a large amount of solid was precipitated, filtered, and the filter cake was washed with ethyl acetate for 3 times, the filtrate and the washings were combined, and the organic phase was extracted by ethyl acetate, and then washed with sodium carbonate and saturated saline in turn.

Under the condition of room temperature and stirring, 5 ml of 6N hydrochloric acid was dropped into the above organic phase and stirred to precipitate the crystal for 3 h. A white solid was obtained by filtration, recrystallised from ethanol and dried, 2.3 g of bromohexine hydrochloride was obtained, yield: 78%.

Product Method of Bulk Bromhexine Hcl.

There are various process routes. One of these is to use o-toluidine as a raw material, which is first brominated to produce 2,4-dibromo-6-toluidine, which is reacted with ethanoic anhydride to acetylate the amino group to produce N,N-diacetyl-2,4-dibromo-6-methylaniline; this protects the amino group, which is then brominated once more to produce N,N-diacetyl-2,4-dibromo-6-bromomethylaniline; which is condensed with N-methylcyclohexylamine to N,N-diacetyl-6-(N-methylcyclohexylamino)methylaniline. 2,4-dibromo-6-(N-methyl)cyclohexylaminomethylaniline. Finally, the acetyl group is hydrolysed with hydrochloric acid to remove the acetyl group and form a salt to obtain the finished product.