Description
4-HOBA is an isomer of the isoketal scavenger 2-HOBA that has reduced efficacy as an isoketal scavenger. Unlike 2-HOBA, 4-HOBA has no effect on hypertension induced by angiotensin II in mice. 4-HOBA has been used as a negative control for the activity of 2-HOBA and related compounds in a mouse model of hypertension.
Chemical Properties
4-Hydroxybenzylamine, also known as tyramine and p-hydroxyphenethylamine, is a white or off-white or light green solid. Tyramine, a compound originally isolated from ergot alkaloids and decomposed animal tissues, is an important synthetic drug intermediate.
Uses
4-Hydroxybenzylamine (cas# 696-60-6) is a compound useful in organic synthesis.
Definition
ChEBI: 4-Hydroxybenzylamine is an aromatic amine.
Preparation
Synthesis of 4-Hydroxybenzylamine:Ammonia is passed into 500 ml of ethanol at 10° C. until saturation is reached, 122.1 g=1 mole of p-hydroxybenzaldehyde, 20 g of Raney nickel and 0.1 ml of concentrated sulfuric acid are added and the mixture is stirred in an autoclave for 6 hours at room temperature and under a hydrogen pressure of 100 atmospheres. After releasing the pressure, the catalyst is filtered off and the filtrate is boiled up with active charcoal, filtered and concentrated. The residue is recrystallized from a mixture of ethanol and ether. This gives 104 g (85% of theory), melting point: 104° C.
Literature source US04391805
Synthesis
Preparative Example A: Synthesis of sodium 4-((2-aminopyridine-3-carbonyl)amino)methyl)phenol. To a solution of 4-hydroxybenzaldehyde (10 g, 81.9 mmol) in methanol (45 mL) was added nickel ryenne (3 g) and 7N aqueous ammonia solution (45 mL). The reaction mixture was stirred for 21 hours at room temperature under hydrogen atmosphere (1 atm). Upon completion of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad and the filtrate was concentrated to afford 4-aminomethylphenol (10 g, quantitatively) as a light green solid. Subsequently, 2-aminonicotinic acid (3.0 g, 21.7 mmol) was dissolved in N,N-dimethylformamide (30 mL), 1-hydroxybenzotriazole (3.51 g, 26 mmol) and (3-dimethylaminopropyl)-ethylcarbodiimide (4.04 g, 26 mmol) were added, and the solution was cooled to 0°C. To this solution, 4-aminomethylphenol (3.0 g , 21.7 mmol) to a solution of N,N-dimethylformamide (20 mL) and the reaction mixture was stirred for 18 hours at room temperature. Upon completion of the reaction, the reaction solution was partitioned into brine and the organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was dissolved in ethyl acetate, filtered through silica gel and the filtrate was concentrated. The residue was dissolved in methanol (90 mL), 1N sodium hydroxide solution (17.8 mL, 17.8 mmol) was added and stirred at room temperature for 1.5 hours. The reaction solution was concentrated in vacuum to give 4-hydroxybenzylamine (5.66 g) as a light yellow solid.
References
[1] Patent: EP1782811, 2007, A1. Location in patent: Page/Page column 46-47
[2] Patent: EP1669348, 2006, A1. Location in patent: Page/Page column 55
[3] Patent: CN105481701, 2016, A. Location in patent: Paragraph 0016
[4] Patent: WO2007/74386, 2007, A2. Location in patent: Page/Page column 8
[5] Patent: US2009/177008, 2009, A1. Location in patent: Page/Page column 2-3
