18683-91-5Relevant articles and documents
Preparation method of ambroxol hydrochloride
-
, (2021/06/23)
The invention discloses a preparation method of ambroxol hydrochloride, which comprises the steps of 1) reacting (A) o-aminodibromobenzaldehyde (I) with (E)-p-aminocyclohexanol (II) to obtain Schiff base; 2) reducing a carbon-nitrogen double bond C = N by (E)-4-[(2-amino-3, 5-dibromobenzylidene) amino] cyclohexanol to obtain ambroxol; and 3) salifying to obtain the finished product ambroxol hydrochloride (compound 1). The route is simple, the product is obtained through condensation, reduction and salification, aldehyde and amido react to generate Schiff base, and the reaction yield is relatively high; and in the reduction reaction of ambroxol, a sodium borohydride zinc chloride complexing system is adopted, the catalytic effect is better, and the production cost is further reduced. The method has the advantages of simple process, low safety and environmental protection risk, easily available raw materials, simple equipment requirements, very little generated wastewater, and easy treatment of three wastes to reach the standard.
Preparation method and application of 2-amino-3,5-bibromobenzyl intermediate compound
-
, (2019/01/14)
The invention provides a preparation method of a 2-amino-3,5-bibromobenzyl intermediate compound and further discloses an application of the 2-amino-3,5-bibromobenzyl intermediate compound in preparation of bromhexine and ambroxol. A cheap and available raw material 2-amino-3,5-dibromobenzaldehyde is adopted, 2-amino-3,5-dibromobenzyl alcohol is obtained through reduction, and the reaction condition is milder; N'N-carbonyldiimidazole is used for activating hydroxyl of 2-amino-3,5-dibromobenzyl alcohol to produce active ester, and the active ester is subjected to a condensation reaction with N-methylcyclohexylamine and trans-p-aminocyclohexanol to produce corresponding products respectively. The preparation method has the advantages that the reproducibility is good, the process is simple, the product purity is high and potential gene poison impurities can be avoided, and the medication safety of the 2-amino-3,5-bibromobenzyl intermediate compound can be further improved.
Synthesis, structural characterization and Hirshfeld analysis studies of three novel co-crystals of trans-4-[(2-amino-3,5-dibrobenzyl) amino] cyclohexanol with hydroxyl benzoic acids
Ma, Yu-Heng,Lou, Ming,Sun, Qing-Yang,Ge, Shu-Wang,Sun, Bai-Wang
, p. 111 - 120 (2015/02/05)
Combination of active pharmaceutical ingredients, trans-4-[(2-amino-3,5-dibrobenzyl) amino] cyclohexanol (AMB) and some organic acids, e.g., p-hydroxybenzoic acid (PHBA), m-hydroxybenzoic acid (MHBA), and 3,4-dihydroxy benzoic acid (DHBA), yield three novel co-crystals characterized by X-ray single-crystal, Fluorescence spectroscopy and thermal analysis (DSC and TGA), which included co-crystal 1 with 2:2: 1 stoichiometry of AMB, PHBA and H2O, co-crystal 2 with 1:1 stoichiometry of AMB and MHBA, and co-crystal 3 with 1:1:1 stoichiometry of AMB, DHBA and CH3OH. Constituents of the co-crystalline phase were also investigated in terms of Hirshfeld surfaces. In the crystal lattice, a three-dimensional hydrogen-bonded network is observed, including formation of a two-dimensional molecular scaffolding motif. Hirshfeld surfaces and fingerprint plots of three co-crystals show that structures are stabilized by H?H, N-H?O, H?Br and C?H intermolecular interactions. Besides, the studies of the solubility showed that this co-crystal strategy could promote the solubility of AMB and follow the order: co-crystal 1 co-crystal 2 co-crystal 3.