Clonidine hydrochloride CAS 4205-91-8
Introduction：Basic information about Clonidine hydrochloride CAS 4205-91-8, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Clonidine hydrochloride Basic information
| Product Name: | Clonidine hydrochloride |
| Synonyms: | CLONIDINE HCL;CLONIDINE HYDROCHLORIDE;DIXARIT;2-[2,6-DICHLOROANILINE]-2-IMIDAZOLINE HYDROCHLORIDE;2-(2,6-DICHLOROANILINO)-2-IMIDAZOLINE, HCL;2-(2,6-DICHLOROANILINO)-2-IMIDAZOLINE HYDROCHLORIDE;2-(2,6-DICHLOROPHENYLAMINO)-2-IMIDAZOLINE HYDROCHLORIDE;katapresan |
| CAS: | 4205-91-8 |
| MF: | C9H10Cl3N3 |
| MW: | 266.55 |
| EINECS: | 224-121-5 |
| Product Categories: | CATAPRES;Other APIs;Adrenoceptor;Amines;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;4205-91-8 |
| Mol File: | 4205-91-8.mol |
Clonidine hydrochloride Chemical Properties
| Melting point | 312 °C |
| storage temp. | 2-8°C |
| solubility | H2O: 50 mg/mL, clear, colorless |
| form | solid |
| color | white |
| PH | pH(50g/l, 25℃) : 3.5～6.0 |
| Water Solubility | Soluble in water (50 mg/ml), DMSO (75 mM), methanol, chloroform (slightly), and dehydrated alcohol. |
| Merck | 14,2390 |
| BRN | 4163525 |
| BCS Class | 1 (LogP), 3 (CLogP) |
| Stability: | Hygroscopic |
| Major Application | pharmaceutical (small molecule) |
| InChI | InChI=1S/C9H9Cl2N3.ClH/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9;/h1-3H,4-5H2,(H2,12,13,14);1H |
| InChIKey | GLEWMLFXCSBZLK-UHFFFAOYSA-N |
| SMILES | C1(=C(Cl)C=CC=C1Cl)NC1=NCCN1.Cl |
| CAS DataBase Reference | 4205-91-8(CAS DataBase Reference) |
| EPA Substance Registry System | 1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-, hydrochloride (1:1) (4205-91-8) |
Safety Information
| Hazard Codes | T+ |
| Risk Statements | 25-26 |
| Safety Statements | 22-26-28-36/37/39-45 |
| RIDADR | UN 2811 6.1/PG 1 |
| WGK Germany | 3 |
| RTECS | NJ2490000 |
| F | 10 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| HS Code | 2933290000 |
| Storage Class | 6.1A - Combustible acute toxic Cat. 1 and 2 very toxic hazardous materials |
| Hazard Classifications | Acute Tox. 1 Inhalation Acute Tox. 3 Oral |
| Toxicity | LD50 in mice, rats (mg/kg): 328, 270 orally; 18, 29 i.v. (Walland) |
| Chemical Properties | White Solid |
| Originator | Catapresan,Boehringer,Ingelheim,1966 |
| Uses | Clonidine hydrochloride tablets are indicated in the treatment of hypertension. It has found new uses, including treatment of some types of neuropathic pain, opioid detoxification, sleep hyperhidrosis, anaesthetic use, and off-label, to counter the side effects of stimulant medications such as methylphenidate or amphetamine. It is becoming a more accepted treatment for insomnia, as well as for relief of menopausal symptoms. Clonidine(4205-91-8) is increasingly used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD). |
| Uses | `a2-adrenoceptor agonist, imidazoline receptor ligand, anti-hypertensive |
| Uses | In shaving soaps. |
| Uses | Labelled Clonidine. α2-Adrenergic agonist. Antihypertensive; analgesic for neuropathic pain. |
| Definition | ChEBI: Clonidine hydrochloride is a dichlorobenzene. |
| Manufacturing Process | N-(2,6-dichlorophenyl)thiourea (MP 149°C) was prepared in customarymanner from 2,6-dichloroaniline (Organic Synthesis III, 262-263) andammonium thiocyanate. 16.0 g of this thiourea derivative were refluxed for 2.5 hours together with 16 g of methyl iodide in 150 cc of methanol.Thereafter, the methanol was evaporated out of the reaction mixture in vacuo,leaving as a residue 22 g of N-(2,6-dichlorophenyl)-S-methyl-isothiouroniumhydroiodide of the formula having a melting point of 170°C. The entire residuewas then admixed with an excess (120%) above the molar equivalent ofethylenediamine, and the mixture was heated for about one hour at 130° to150°C. Methyl mercaptan was given off. Thereafter, the reaction mixturecomprising 2-(2',6'-dichloroanilino)-1,3-diazacyclopentene-(2) hydroiodide wastaken up in hot dilute acetic acid, and the resulting solution was made alkalinewith 2 N NaOH. A precipitate formed which was separated by vacuumfiltration, washed with water and dried. 4.0 g of 2-(2',6'-dichloroanilino)-1,3-diazacyclopentene-(2) were obtained. The product had a melting point of130°C. The free base was then dissolved in absolute methanol, and the resultingsolution was then adjusted to an acid pH value with an ethereal hydrochloricacid solution. The acidified solution was purified with charcoal and then dryether was added thereto until crystallization took place. The hydrochloride,prepared in this customary manner, had a melting point of 305°C according toUS Patent 3,202,660 |
| Brand name | Catapres (Boehrin-ger Ingelheim); Duraclon (Xanodyne). |
| Therapeutic Function | Antihypertensive |
| Synthesis Reference(s) | Synthesis, p. 64, 1987 DOI: 10.1055/s-1987-27847 |
| General Description | Clonidine hydrochloride, 2-[(2,6-dichlorophenyl)imino]imidazolidine monohydrochloride(Catapres), was the first antihypertensive known to acton the CNS. It was synthesized in 1962 as a derivativeof the known -sympathomimetic drugs naphazoline andtolazoline, potential nasal vasoconstrictors, but instead itproved to be effective in the treatment of mild-to-severe hypertension.Clonidine hydrochloride acts by both peripheral andcentral mechanisms in the body to affect blood pressure. Itstimulates the peripheral -adrenergic receptors to producevasoconstriction, resulting in a brief period of hypertension. |
| Biological Activity | Prototypical I 1 imidazoline receptor ligand. α 2 -adrenergic receptor agonist. Antihypertensive. |
| Biochem/physiol Actions | Clonidine hydrochloride is used for management of hypertension in pregnant women. In addition, it also acts as a therapeutic for neonatal abstinence syndrome. Clonidine hydrochloride binds to central α-adrenergic receptors and reduces the efferent sympathetic neuronal vasoconstrictor tone to the heart, kidneys and peripheral vasculature leading to vasodilatation and reduction in the blood pressure. |
| Clinical Use | Clonidine hydrochloride acts by both peripheral andcentral mechanisms in the body to affect blood pressure. Itstimulates the peripheral α-adrenergic receptors to producevasoconstriction, resulting in a brief period of hypertension.Clonidine hydrochloride acts centrally to inhibitthe sympathetic tone and cause hypotension that is ofmuch longer duration than the initial hypertensive effect.Administration of clonidine hydrochloride thus produces abiphasic change in blood pressure, beginning with a briefhypertensive effect and followed by a hypotensive effectthat persists for about 4 hours. This biphasic response isaltered by dose only. Larger doses produce a greater hypertensiveeffect and delay the onset of the hypotensiveproperties of the drug. Clonidine hydrochloride acts on 2-adrenoreceptors located in the hindbrain to produce itshypotensive action. Clonidine hydrochloride also acts centrallyto cause bradycardia and to reduce plasma levels ofrenin. Sensitization of baroreceptor pathways in the CNSappears to be responsible for the bradycardia transmittedby way of the vagus nerve. The central mechanism that resultsin decreased plasma renin is not known, however.The hypotensive properties of clonidine in animals can beblocked by applying -adrenergic blocking agents directlyto the brain. |
| Drug interactions | Potentially hazardous interactions with other drugs Antidepressants: tricyclics antagonise hypotensive effect and also increase risk of hypertension on clonidine withdrawal; increased hypotensive effect with MAOIs; hypotensive effect possibly antagonised by mirtazapine. Beta-adrenoreceptor antagonists: increased risk of hypertension on withdrawal. Ciclosporin: may increase ciclosporin levels. Sympathomimetics: possibly increased risk of hypertension with adrenaline and noradrenaline; serious adverse effects reported with methylphenidate. |
| Metabolism | About 50% of a of clonidine dose is metabolised in the liver. It is excreted in the urine as unchanged drug and metabolites, 40-60% of an oral dose being excreted in 24 hours as unchanged drug; about 20% of a dose is excreted in the faeces, probably via enterohepatic circulation. |
| storage | Store at RT |
| Purification Methods | This antihypertensive is recrystallised from EtOH/Et2O and dried in a vacuum (solubility in H2O is 5%). The free base has m 124-125o and is recrystallised from hexane. [Jen et al. J Med Chem 18 90 1975, NMR: Jackman & Jen J Am Chem Soc 97 2811 1975.] |
| References | [1] Patent: CN107915679, 2018, A. Location in patent: Paragraph 0050; 0057; 0058; 0063; 0064 |
Clonidine hydrochloride Preparation Products And Raw materials
| Raw materials | 2,6-Dichloroaniline-->Iodomethane-->Hydrogen-->thiocyanate-->Ethylenediamine-->Ethanol-->DICHLORPHENAMIDE BULK POWDER-->CLONIDINE-->Hydrochloric acid-->Water |
