5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol CAS 23031-25-6
Introduction：Basic information about 5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol CAS 23031-25-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol Basic information
| Product Name: | 5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol |
| Synonyms: | Bambuterol EP Impurity A;5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol;(R)-α-[(tert-Butylamino)methyl]-3,5-dihydroxybenzyl alcohol;(S)-α-[(tert-Butylamino)methyl]-3,5-dihydroxybenzyl alcohol;5-[(S)-1-Hydroxy-2-(tert-butylamino)ethyl]benzene-1,3-diol;rac-5-[(R*)-2-[(1,1-Dimethylethyl)amino]-1-hydroxyethyl]-1,3-benzenediol;C07129;Terbutaline & Terbutaline Sulfate |
| CAS: | 23031-25-6 |
| MF: | C12H19NO3 |
| MW: | 225.28 |
| EINECS: | 245-385-8 |
| Product Categories: | |
| Mol File: | 23031-25-6.mol |
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol Chemical Properties
| Melting point | 119-122° |
| Boiling point | 366.8°C (rough estimate) |
| density | 1.0951 (rough estimate) |
| refractive index | 1.4596 (estimate) |
| storage temp. | Refrigerator |
| solubility | DMSO (Slightly), Methanol (Slightly) |
| form | Solid |
| pka | pKa 8.70(H2Ot = 25I = 0.01) (Uncertain);10.09(H2Ot = 25I = 0.01) (Uncertain) |
| color | White to Off-White |
| InChI | InChI=1S/C12H19NO3/c1-12(2,3)13-7-11(16)8-4-9(14)6-10(15)5-8/h4-6,11,13-16H,7H2,1-3H3 |
| InChIKey | XWTYSIMOBUGWOL-UHFFFAOYSA-N |
| SMILES | C1(O)=CC(C(O)CNC(C)(C)C)=CC(O)=C1 |
| CAS DataBase Reference | 23031-25-6 |
Safety Information
| Description | Terbutaline is a synthetic congener of adrenaline that acts at theβ2-receptor causing bronchodilation and tocolytic effects. Itwas the first β2-selective adrenoreceptor agonist in generalclinical use. In 2011, the Food and Drug Administration (FDA)placed a black-boxed warning on terbutaline stating that terbutalineinjections should not be given to pregnant women norshould be used to prevent preterm labor or for long-term(greater than 48–72 h) treatment of preterm labor. Oral terbutalineshould not be used at all due to its potential forcardiac toxicity and death. Terbutaline is on the World Anti-Doping Agency’s list of prohibited drugs for Olympic athletes(except when a Therapeutic Use Exemption has been granted inadvance and when used by inhalation). |
| Description | Terbutaline is a short-acting β2-adrenergic receptor (β2-AR) agonist and an active metabolite of bambuterol . It binds to β1-, β2-, and β3-ARs (Ki = 31.3, 15.4, and 79.8 nM, respectively) and selectively increases adenylyl cyclase activity in CHO cell membranes expressing recombinant human β2- or β3- over β1-ARs at concentrations 100-fold greater than the respective Ki values. Terbutaline inhibits histamine release induced by ovalbumin in isolated guinea pig lung mast cells. It also inhibits airway obstruction induced by methacholine (acetyl-β-methylcholine; ) or leukotriene D4 (LTD4; ) in anesthetized guinea pigs. Formulations containing terbutaline have been used in the treatment of asthma. |
| Originator | Bricanyl,Pharma-Stern,W. Germany,1971 |
| Uses | Terbutaline is used as a bronchodilator and for the preventionof premature labor. The FDA has added boxed warnings toterbutaline for its use as a tocolytic for the prevention ofpreterm labor. Unlabeled use includes treatment of hyperkalemia.Terbutaline is being studied for its use in treatment ofcertain neuromuscular disorders as well. |
| Uses | Terbutaline is a beta-adrenoceptor agonist used to treat asthma and premature labor. |
| Uses | Terbutaline is used for preventing and relieving bronchospasms in bronchial asthma, chronic bronchitis, pulmonary emphysema, and other broncho-pulmonary diseases. |
| Definition | ChEBI: A member of the class of phenylethanolamines that is catechol substuted at position 5 by a 2-(tert-butylamino)-1-hydroxyethyl group. |
| Indications | Terbutaline (Brethine, Bricanyl) is a relatively specificβ2-adrenoceptor agonist.Terbutaline can prevent premature labor, especially inindividuals who are more than 20 weeks into gestationand have no indication of ruptured fetal membranes orin whom labor is not far advanced. Its effectiveness inpremature labor after 33 weeks of gestation is much lessclear. Terbutaline can decrease the frequency, intensity,and duration of uterine contractions through its abilityto directly stimulate β2-adrenoceptors. While it appearsto be especially selective for β2-receptor activation,terbutaline does have some β1 activity as well. |
| Manufacturing Process | To a solution of 32 g of benzyl-t-butylamine in 300 ml of absolute ethanol atreflux temperature was added 32 g of 3,5-dibenzyloxy-?-bromoacetophenonein 10 ml of dry benzene. The mixture was refluxed for 20 hours and thenevaporated. When absolute ether was added to the residue, benzyl-tbutylaminehydrobromide was precipitated. The precipitated compound wasfiltered off and to the filtrate was added an excess of 2 N sulfuric acid. Thiscaused precipitation of the hydrogen sulfate of 3,5-dibenzyloxy-?-(benzyl-tbutylamino)-acetophenone which was recrystallized from acetone/ether. If the product is crystallized from different organic solvents, the melting point willvary with the type and amount of solvent of crystallization, but the productcan be used directly for hydrogenation. 15 g of 3,5-dibenzyloxy-?-(benzyl-t-butylamino)-acetophenone hydrogensulfate in 200 ml of glacial acetic acid were hydrogenated in a Parr pressurereaction apparatus in the presence of 1.5 g of 10% palladium charcoal at50°C and 5 atmospheres pressure. The reaction time was 5 hours. Thecatalyst was filtered off, the filtrate was evaporated to dryness and thehydrogen sulfate of 1-(3',5'-dihydroxyphenyl)-2-(t-butylamino)-ethanol wasreceived. This compound is hygroscopic, but it can be transformed into anonhygroscopic sulfate in the following manner. The hydrogen sulfate was dissolved in water and the pH of the solution wasadjusted to 5.6 (pH-meter) with 0.1 N sodium hydroxide solution. The watersolution was evaporated to dryness and the residue dried with absoluteethanol/benzene and once more evaporated to dryness. The remaining crystalmixture was extracted in a Soxhlet extraction apparatus with absolutemethanol. From the methanol phase the sulfate of 1-(3',5'-dihydroxyphenyl)-2-(t-butylamino)-ethanol crystallized. Melting point 246°C to 248°C. |
| Therapeutic Function | Bronchodilator |
| Mechanism of action | Terbutaline is a synthetic sympathomimetic amine. It is one of the most selective direct–actingstimulants of β2-adrenoreceptors. It stimulates smooth muscle β2-adrenoreceptors in thebronchi, relaxing them and relatively minutely acting on the β1—receptors of the heart. |
| Clinical Use | Terbutaline should be initially used only in anappropriate hospital setting where any obstetric complicationscan be readily addressed. After initial administration,it can be used in the outpatient setting.Concomitant use of β2-adrenergic agonists and corticosteroidshave additional diabetic effects and mayrarely lead to pulmonary edema.The combination of β2-adrenergic agonists and magnesium sulfate can causecardiac disturbances, while coadministration of terbutalinewith other sympathomimetics can lead to the potentiationof the actions of the latter drugs. |
| Side effects | Terbutaline is frequently used in the management ofpremature labor, although it has not been marketed forsuch use. Its effectiveness, side effects, precautions, andcontraindications are similar to those of all β2-adrenergicagonists. Terbutaline can cause tachycardia, hypotension,hyperglycemia, and hypokalemia. It can begiven orally in addition to subcutaneous or intravenousadministration. |
| Synthesis | Terbutaline, |á-[(tert-butylamino)methyl]-3,5-dihydroxybenzylic alcohol(11.1.14), differs from the examined compounds mainly in the location of hydroxylgroups in the benzene ring, and is synthesized by brominating 3,5-dibenzyloxy|ácetophenone into the appropriate 3,5-dibenzyloxybromoacetophenone (11.1.12), which isreacted with N-benzyl-N-tert-butylamine, giving the aminoketone (11.1.13). Reduction of this product by hydrogen over a palladium catalyst leads to terbutaline (11.1.14) [16¨C18]. |
| Environmental Fate | Terbutaline is administered as the sulfate. It is a white to graywhite,crystalline powder; nearly odorless or with the faint odorof acetic acid. Terbutaline has a slightly bitter taste. It hasa melting point of 247°C. Terbutaline sulfate is soluble at 1 gper 1.5 ml water or 250 ml of ethanol. It is soluble in 0.1 Nhydrochloric acid, slightly soluble in methanol, and insolublein chloroform. While terbutaline is stable under normalconditions as a solid, it is unstable in light. Terbutaline isdegraded through oxidative processes; this is enhanced in thepresence of trace levels of metals and in the presence of oxygen. No information is currently available on breakdown in soil,groundwater, or surface water. |
| Toxicity evaluation | The primary mechanism of terbutaline is the stimulation ofadenyl cyclase, which catalyzes cyclic adenosine monophosphate(AMP) from adenosine triphosphate (ATP). In theliver, buildup of cyclic AMP stimulates glycogenolysis and anincrease in serum glucose. In skeletal muscle, this processresults in increased lactate production. Direct stimulus ofsodium/potassium ATPase in skeletal muscle produces a shiftof potassium from the extracellular space to the intracellularspace. Relaxation of smooth muscle produces a dilation of thevasculature supplying skeletal muscle, which results in a dropin diastolic and mean arterial pressure (MAP). Terbutaline hasgreater b2 selectivity, but overdose will have both β1 and β2activity. Tachycardia occurs as a reflex to the drop in MAP or asa result of β1 stimulus. β1-Adrenergic receptors in the locusceruleus also regulate norepinephrine-induced inhibitoryeffects, resulting in agitation, restlessness, and tremor. |
| References | [1] C HOFFMANN. Comparative pharmacology of human beta-adrenergic receptor subtypes–characterization of stably transfected receptors in CHO cells.[J]. Naunyn-Schmiedeberg’s archives of pharmacology, 2004, 369 2: 151-159. DOI: 10.1007/s00210-003-0860-y [2] H Y LAU C K L P L Wong. Effects of beta 2-adrenergic agonists on isolated guinea pig lung mast cells.[J]. Agents and Actions, 1994, 42 3-4: 92-94. DOI: 10.1007/bf01983471 [3] O A OLSSON L ? S. New lipophilic terbutaline ester prodrugs with long effect duration.[J]. Pharmaceutical Research, 1984, 1 1: 19-23. DOI: 10.1023/a:1016322524471 [4] SALONEN R O. Actions of bronchodilator drugs, glucocorticoid, and their combinations on airways in rats and guinea pigs[J]. Basic & Clinical Pharmacology & Toxicology, 1985, 57 s3: 6-38. DOI: 10.1111/j.1600-0773.1985.tb03577.x |
5-(1-Hydroxy-2-tert-butylamino-ethyl)benzene-1,3-diol Preparation Products And Raw materials
| Raw materials | Hydrogen-->Benzeneacetaldehyde, α-oxo-3,5-bis(phenylmethoxy)--->3,5-Dibenzyloxy terbutalline-->3,5-Dibenzyloxyacetophenone-->2-BROMO-1-(3,5-DIHYDROXYPHENYL)ETHANONE-->Benzaldehyde, 3,5-bis(acetyloxy)--->3,5-Dihydroxyacetophenone-->3,5-Dihydroxybenzaldehyde-->tert-Butylamine |
