31828-71-4

Basic information

• Product Name: 1-(2,6-Dimethylphenoxy)-2-propanamine
• Synonyms: 1-(2,6-dimethylphenoxy)-2-propanamin;1-methyl-2-(2,6-xylyloxy)-ethylamin;1-Methyl-2-(2,6-xylyloxy)ethylamine;2-Propanamine, 1-(2,6-dimethylphenoxy)-;Ethylamine, 1-methyl-2-(2,6-xylyloxy)-;Mexilitine;1-(2,6-xylyloxy)-2-aminopropane hydrochloride;MEXILETIN
• CAS NO: 31828-71-4
• Molecular Formula: C₁₁H₁₇NO
• Molecular Weight: 179.25878
• EINECS: 250-825-7
• Mol File: 31828-71-4.mol
• Article Data: 31

Chemical Properties

• Melting Point: 203-205 °C
• Boiling Point: 271.5 °C at 760 mmHg
• Flash Point: 112.2 °C
• Appearance: white/powder
• Density: 0.979 g/cm³
• Vapor Pressure: 0.00642mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: ethanol: 50 mg/mL
• PKA: pKa 9.14± 0.01(H2O,t =25±0.2,I=0.01(NaCl))(Approximate)
• CAS DataBase Reference: 1-(2,6-Dimethylphenoxy)-2-propanamine(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(2,6-Dimethylphenoxy)-2-propanamine(31828-71-4)
• EPA Substance Registry System: 1-(2,6-Dimethylphenoxy)-2-propanamine(31828-71-4)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• RIDADR: 3249
• WGK Germany: 3
• RTECS: KR9300000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 31828-71-4(Hazardous Substances Data)

Usage

Originator

Mexitil,Boehringer Ingelheim,US,1976

Uses

Different sources of media describe the Uses of 31828-71-4 differently. You can refer to the following data:
1. Cardiac depressant (anti-arrhythmic).
2. Mexiletine is used for ventricular extrasystole and ventricular tachycardia, and ventricular fibrillation (including during the severe period of myocardial infarction).
3. Mexiletine is a useful analgesia.It is used in treatment of amyotrophic lateral sclerosis comprising administering a bile acid and a phenylbutyrate compound and an additional therapeutic agent.

Definition

ChEBI: An aromatic ether which is 2,6-dimethylphenyl ether of 2-aminopropan-1-ol.

Manufacturing Process

The sodium salt of dimethyl phenol was reacted with chloroacetone and this product with hydroxylamine to give the starting material.245 g of this 1-(2',6'-dimethyl-phenoxy)-propanone-(2)-oxime were dissolved in 1,300 cc of methanol, and the solution was hydrogenated at 5 atmospheres gauge and 60°C in the presence of Raney nickel. After the calculated amount of hydrogen had been absorbed, the catalyst was filtered off, the methanol was distilled out of the filtrate,and the residue, raw 1-(2',6'-dimethylphenoxy)-2-amino-propane, was dissolved in ethanol. The resulting solution was acidified with ethereal hydrochloric acid, the acidic solution was allowed to cool, and the precipitate formed thereby was collected by vacuum filtration. The filter cake was dissolved in ethanol and recystallized therefrom by addition of ether. 140.5 g (51.5% of theory) of a substance having a melting point of 203°C to 205°C were obtained, which was identified to be 1-(2',6'- dimethyl-phenoxy)-2-anino-propane hydrochloride.

Brand name

Mexitil (Boehringer Ingelheim).

Therapeutic Function

Antiarrhythmic

Clinical Use

Mexiletine (Mexitil) is an antiarrhythmic agent with pharmacological and antiarrhythmic properties similar to those of lidocaine and tocainide. Like tocainide,mexiletine is available for oral administration. Mexiletine is useful as an antiarrhythmic agent in the management of patients with either acute or chronic ventricular arrhythmias.While it is not at present an indication for use, there is interest in using mexiletine to treat the congenital long QT syndrome when an abnormality in the SCN5A gene (LQTS 3) has been found.

Side effects

A very narrow therapeutic window limits mexiletine use. The first signs of toxicity manifest as fine tremor of the hands, followed by dizziness and blurred vision. Hypotension, sinus bradycardia, and widening of the QRS complex have been noted as the most common unwanted cardiovascular effects of IV mexiletine. The side effects of oral maintenance therapy include reversible upper gastrointestinal distress, tremor, lightheadedness, and coordination difficulties. These effects generally are not serious and can be reduced by downward dose adjustment or administering the drug with meals. Cardiovascular adverse effects, which are less common, include palpitations, chest pain, and angina or anginalike pain.

Synthesis

Mexiletine is 1-methyl-2-(2,2-dimethylphenoxy)ethylamine (18.1.11). Mexiletine is synthesized by reacting the sodium salt of 2,6-dimethylphenol with chloroacetone, forming 1-(2,6-dimethylphenoxy)-2-propanone (18.1.9). Reacting this with hydroxylamine gives the corresponding oxime (18.1.10). Reduction of the oximine group using hydrogen over Raney nickel gives mexiletine (18.1.11).

Drug interactions

An upward adjustment in dose may be required when mexiletine is administered with phenytoin or rifampin, since these drugs stimulate the hepatic metabolism of mexiletine, reducing its plasma concentration.

Precautions

Mexiletine is contraindicated in the presence of cardiogenic shock or preexisting second- or third-degree heart block in the absence of a cardiac pacemaker. Caution must be exercised in administration of the drug to patients with sinus node dysfunction or disturbances of intraventricular conduction.

InChI:InChI:1S/C11H17NO/c1-8-5-4-6-9(2)11(8)13-7-10(3)12/h4-6,10H,7,12H2,1-3H3

Upstream product

• 1092493-53-2 tert-butyl (1-(2,6-dimethylphenoxy)propan-2-yl)carbamate 
• 53012-41-2 (2,6-dimethylphenoxy)-2-propanone 
• 5370-01-4 (rac)-mexiletine hydrochloride 
• 1100753-75-0 N-octanoylglycine 2,2,2-trifluoroethyl ester 
• 1093278-41-1 (R)-2-[(2,6-dimethylphenoxy)methyl]-1-[(R)-1-phenylethyl]aziridine 
• 1051392-84-7 (E)-1-(2,6-dimethyl-phenoxy)-propan-2-one O-benzyl oxime 
• 252049-70-0 (2RS)-N-(1-(2',6'-dimethylphenoxy)-2-propyl)-tetrahydropyranyl-(R)-mandelamide 
• 68164-74-9 1-(2,6-Dimethylphenoxy)-2-methansulfonyloxy-propan 
• 72806-53-2 1-(2,6-Dimethylphenoxy)-2-azido-propan 
• 61102-09-8 (RS)-1-(2,6-dimethylphenoxy)propan-2-ol 
• 576-26-1 2.6-dimethylphenol 
• 265994-88-5 (-)-(R)-2-[2-(2,6-dimethylphenoxy)-1-methylethyl]-1H-isoindole-1,3(2H)-dione 
• 252049-71-1 (2R)-N-(1-(2',6'-dimethylphenoxy)-2-propyl)-(R)-mandelamide 
• 21078-03-5 1,3-dimethyl-2-(prop-2-yn-1-yloxy)benzene 

Downstream Products

• 94991-72-7 (S)-mexiletine 
• 31828-71-4 (R)-mexiletine 
• 252049-72-2 (2S)-N-(1-(2',6'-dimethylphenoxy)-2-propyl)-(R)-mandelamide 
• 252049-71-1 (2R)-N-(1-(2',6'-dimethylphenoxy)-2-propyl)-(R)-mandelamide 
• 1105713-18-5 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(2,6-dimethyl-phenoxy)-1-methyl-ethyl]amide 
• 1105713-19-6 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4-bromo-2,6-dimethyl-phenoxy)-1-methyl-ethyl]amide 
• 53012-41-2 (2,6-dimethylphenoxy)-2-propanone 
• 1100754-10-6 N-(((S)-1-(2,6-dimethylphenoxy)propan-2-ylcarbamoyl)methyl)octanamide 
• 1100754-02-6 tert-butyl (R)-1-(2,6-dimethylphenoxy)propan-2-ylcarbamate 
• 1190867-98-1 C₂₁H₃₄N₂O₃ 
• 1517-69-7 (R)-1-phenylethanol 
• 107832-32-6 (R)-1-phenylethyl propionate 
• 120-45-6 (S)-1-phenylethyl propionate 
• 219119-81-0 (S)-1-(4-methoxyphenyl)ethyl propionate 

Relevant articles and documents

Deracemization of mexiletine biocatalyzed by ω-transaminases

(S)- as well as (R)-mexiletine [1-(2,6-dimethylphenoxy)-2-propanamine], a chiral orally effective antiarrhythmic agent, was prepared by deracemizatlon starting from the commercially available racemic amine using ω-transaminases In up to >99% ee and conver

Enantiodivergent syntheses of (+)- and (?)-1-(2,6-dimethylphenoxy)propan-2-ol: A way to access (+)- and (?)-mexiletine from D-(+)-mannitol

Chiron approach was used to acquire optically pure (R)- and (S)-1-(2,6-dimethylphenoxy)propan-2-ol, immediate precursors of (S)- and (R)-mexiletines, respectively. Two different routes were followed from a D-mannitol-derived optically pure common precursor to get the enantiomeric alcohols separately. Comparison of their specific rotation values with the corresponding literature values as well as exact mirror-image relationship between their CD curves proved their high enantiopurity. These alcohols were then transformed to the corresponding amine-drugs in an efficient one-step process instead of two steps described in the literature.

Preparation of polar group derivative β-cyclodextrin bonded hydride silica chiral stationary phases and their chromatography separation performances

Three novel β-cyclodextrin compounds derived with piperidine which is flexible, L-proline containing a chiral center, ionic liquid with 3,5-diamino-1,2,4-triazole as the cation were designed and synthesized as chiral selectors for enantiomer separation, whose name were (mono-6-deoxy-6-(piperidine)-β-cyclodextrin, mono-6-deoxy-6-(L-proline)-β-cyclodextrin, mono-6-deoxy-6-(3,5-diamino-1,2,4-triazole)-β-cyclodextrin, multi-substituted 3,5-diamino-1,2,4- triazole-(p-toluenesulfonic)-β-cyclodextrin), respectively. In addition, to enhance the polarity of chiral stationary phases, hydrosilylation and silylation reactions were implemented to derive ordinary silica, the common used selector carrier, to hydride silica, whose surface is covered with proton. 31 pyrrolidine compounds and some chiral drugs were tested in both polar organic mobile phase mode and normal mobile phase mode. 6-Deoxy-6-L-proline-β-cyclodextrin-CSP showed satisfactory separations in polar organic mobile phase mode and exihibited a strong separation capability in different pH values; multi-substituted 3,5-diamino-1,2,4-triazole-(p-toluenesulfonic)-β-cyclodextrin-CSP can separate pyrrolidine compounds in both mobile phase modes with high resolutions and separation efficiency compared to commercially available CSPs, making it to be the most valuable object to study. The composition of mobile phase, type of stationary phase as well as the peak problem of chromatograms was discussed deeply.