14542-15-5

Basic information

• Product Name: METHYL 4-METHYLTHIAZOLE-2-CARBOXYLATE
• Synonyms: METHYL 4-METHYLTHIAZOLE-2-CARBOXYLATE;Methyl 4-Methylthiazol-2-carboxylate;Methyl 4-Methyl-2-thiazolecarboxylate;4-Methyl-thiazole-2-carboxylic acid Methyl ester;4-Methyl-2-thiazolecarboxylic acid methyl ester;2-Thiazolecarboxylic acid, 4-methyl-, methyl ester
• CAS NO: 14542-15-5
• Molecular Formula: C₆H₇NO₂S
• Molecular Weight: 157.19
• Mol File: 14542-15-5.mol
• Article Data: 3

Chemical Properties

• Melting Point: 62-67°C
• Boiling Point: 233.933 °C at 760 mmHg
• Flash Point: 95.28 °C
• Appearance: /
• Density: 1.245 g/cm³
• Vapor Pressure: 0.054mmHg at 25°C
• Refractive Index: 1.535
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 0.73±0.10(Predicted)
• CAS DataBase Reference: METHYL 4-METHYLTHIAZOLE-2-CARBOXYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: METHYL 4-METHYLTHIAZOLE-2-CARBOXYLATE(14542-15-5)
• EPA Substance Registry System: METHYL 4-METHYLTHIAZOLE-2-CARBOXYLATE(14542-15-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 14542-15-5(Hazardous Substances Data)

Usage

General Description

Methyl 4-methylthiazole-2-carboxylate is a chemical compound with the molecular formula C6H7NO2S. It is a methyl ester derivative of 4-methylthiazole-2-carboxylic acid, and is commonly used in organic synthesis and as a building block for the production of pharmaceuticals, agrochemicals, and fragrances. METHYL 4-METHYLTHIAZOLE-2-CARBOXYLATE is known for its fruity, nutty, and roasted aroma, making it an important ingredient in the flavor and fragrance industry. It is also used as a reagent in the preparation of various other organic compounds due to its unique chemical properties. Additionally, it is important to handle this compound with caution as it may be harmful if ingested or inhaled.

InChI:InChI=1/C6H7NO2S/c1-4-3-10-5(7-4)6(8)9-2/h3H,1-2H3

Synthetic route

methanol (67-56-1) + 4-methyl-1,3-thiazole-2-carboxylic acid (14542-16-6) → methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5)

Conditions	Yield
With sulfuric acid at 20℃; for 240h;
With hydrogenchloride at 20℃;	2.2 g

4-Methylthiazol-2-carbonsaeure-ethylester (7210-73-3) → methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH, water / 0.08 h / Heating 2: H2SO4 / 240 h / 20 °C View Scheme

4-Methylthiazole (693-95-8) + methanolic hydrogen chloride → methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; methanol; diethyl ether; hexane

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → 4-methyl-1,3-thiazole-2-carbohydrazide (100516-76-5)

Conditions	Yield
With hydrazine hydrate In ethanol at 20℃; for 14h; Inert atmosphere;	82%
With hydrazine hydrate In methanol for 1.5h;	76%
With hydrazine hydrate In methanol

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → O-methyl 4-methylthiazole-2-carbothioate

Conditions	Yield
With Lawessons reagent In para-xylene for 24h; Inert atmosphere; Reflux;	74%

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → 6-chloro-3-(4-methyl-1,3-thiazol-2-yl)-7,8,9,10-tetrahydro-7,10-ethano[1,2,4]triazolo[3,4-a]phthalazine (848774-81-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 76 percent / NH2NH2*H2O / methanol / 1.5 h 2: 17 percent / Et3N*HCl / xylene / 96 h / Heating View Scheme

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → C21H20N6OS

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 76 percent / NH2NH2*H2O / methanol / 1.5 h 2.1: 17 percent / Et3N*HCl / xylene / 96 h / Heating 3.1: NaH / dimethylformamide / 20 °C 3.2: dimethylformamide / 20 °C View Scheme

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → (R)-2-(7-(2,4-dimethoxybenzyl)-8-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)-4-methylthiazole

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 14 h / 20 °C / Inert atmosphere 2: methanol / 8 h / 60 - 70 °C / Inert atmosphere View Scheme

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → (R)-(8-methyl-3-(4-methylthiazol-2-yl)-5,6-dihydro-[1,2,4]-triazolo[4,3-a]pyrazin-7(8H)-yl)(4-(thiophen-2-yl)phenyl)methanone (1429557-35-6)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: hydrazine hydrate / ethanol / 14 h / 20 °C / Inert atmosphere 2.1: methanol / 8 h / 60 - 70 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 0.25 h / 0 - 20 °C / Inert atmosphere 3.2: 0.5 h / Inert atmosphere 4.1: 4-methyl-morpholine / dichloromethane / 0.5 h / 0 - 20 °C / Inert atmosphere 4.2: 0.17 h / 0 - 20 °C / Inert atmosphere View Scheme

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → (R)-4-methyl-2-(8-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)thiazole

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / ethanol / 14 h / 20 °C / Inert atmosphere 2.1: methanol / 8 h / 60 - 70 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 0.25 h / 0 - 20 °C / Inert atmosphere 3.2: 0.5 h / Inert atmosphere View Scheme

methyl 4-methyl-1,3-thiazole-2-carboxylate (14542-15-5) → C13H10N2S2

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Lawessons reagent / para-xylene / 24 h / Inert atmosphere; Reflux 2.1: C19H34O8Rh2 / chloroform / 1 h / 70 °C / Inert atmosphere; Glovebox; Molecular sieve; Sealed tube 2.2: 2 h / 70 °C / Inert atmosphere; Glovebox; Sealed tube View Scheme

Upstream product

• 67-56-1 methanol 
• 14542-16-6 4-methyl-1,3-thiazole-2-carboxylic acid 
• 7210-73-3 4-Methylthiazol-2-carbonsaeure-ethylester 
• 693-95-8 4-Methylthiazole 

Downstream Products

• 100516-76-5 4-methyl-1,3-thiazole-2-carbohydrazide 
• 1429557-35-6 (R)-(8-methyl-3-(4-methylthiazol-2-yl)-5,6-dihydro-[1,2,4]-triazolo[4,3-a]pyrazin-7(8H)-yl)(4-(thiophen-2-yl)phenyl)methanone 

Relevant articles and documents

Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazines as GABAA receptor agonists at the α3 subunit

We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4- triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the 0.3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at α1 and antagonism at α3 (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.

An Infrared Study of Rotational Isomerism in Thiazole-2-carboxylates

A series of alkyl thiazole-2-carboxylates containing a range of substituents at the 4- and 5-positions has been prepared.Solutions of these esters (mostly new compounds) show well resolved doublets in the i.r.C=O region which arise from rotational isomers.The higher wavenumber components are assigned to the more polar carbonyl O,S-anti-s-trans-rotamers and the lower wavenumber components to the carbonyl O,S-syn-s-trans-forms.Small, but systematic, differences between the methyl esters are noted.