4.5-Methylthiazole

Product Name 4.5-Methylthiazole
Alias 4-Methyl-5-thiazole
Einecs 218-500-8
Mininmum Order 1G
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
Price Inquiry sales9@bouling-chem.com
Manufacturer Bouling Chemical Co., Limited
CONTACT NOW

In terms of specification, 4.5-Methylthiazole is supplied with ≥98% purity (GC) and colorless to pale yellow liquid appearance, making it suitable for flavor and fragrance formulations.

Specifications

HS Code	971331
Chemical Formula	C4H5NS
Molar Mass	99.154 g/mol
Appearance	Colorless to pale yellow liquid
Odor	Characteristic, pungent odor
Boiling Point	144 - 145 °C
Melting Point	−45 °C
Density	1.12 g/cm³
Solubility In Water	Slightly soluble
Solubility In Organic Solvents	Soluble in many organic solvents
Flash Point	38 °C
Vapor Pressure	At 25°C, relatively low vapor pressure

As an accredited 4.5-Methylthiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	500g of 4,5 - Methylthiazole packaged in a sealed, corrosion - resistant bottle.
Shipping	4.5 - Methylthiazole is shipped in well - sealed, corrosion - resistant containers. Compliance with hazardous chemical shipping regulations is ensured. Quantity - based packaging is used, safeguarding it during transit to prevent leakage and ensure safety.
Storage	4,5 - Methylthiazole should be stored in a cool, dry, well - ventilated area away from heat sources and open flames. It should be kept in a tightly sealed container to prevent evaporation and exposure to air. Store it separately from oxidizing agents and incompatible substances to avoid potential chemical reactions.

Application of 4.5-Methylthiazole

Addition of 4,5-dimethylthiazole at 2–20 ppm in baked and extruded matrices establishes a roasted-meaty, nutty, and chocolate-like base note that bridges top-note thiols and non-volatile taste enhancers. In cracker and snack seasoning, the compound is listed under FEMA 3274 and JECFA 1035, with regulatory coverage by 21 CFR §172.515 and EU Flavis 15.013. On a Clextral BC45 twin-screw extruder (L/D 32:1), liquid injection occurs post-vent at barrel zone 7, where melt temperature is maintained at 110–150°C. This thermal window drives thiamine degradation and Maillard pathways that couple the thiazole with pyrazines and 2-methyl-3-furanthiol, yielding a savory brown-roast signature. Exceeding 155°C triggers isomerization to 2,4-dimethylthiazole, which introduces a metallic, bitter aftertaste detectable at 0.5 ppb orthonasally. In high-fat systems (>25% total fat), headspace concentration drops by 40–60% due to lipophilic partitioning; microencapsulation in OSA-modified starch (Hi-Cap 100) with a spray-drying inlet of 190°C restores volatile delivery. A pH ceiling of 7.5 is critical: above this value free thiol generation produces sulfurous off-notes. Routine quantitation uses SPME-GC-MS on an Agilent 7890B/5977B with a detection limit of 0.01 ppb and an expanded uncertainty of ±12% (k=2).

Dairy and confectionery applications demand a subtle thiazole insertion to reinforce milky, buttery and caramelic notes. In caramel toffee and milk chocolate, 0.5–8 ppm of 4,5-dimethylthiazole contributes a distinct condensed-milk tallowy character when used alongside vanillin and delta-lactones. The molecule withstands standard indirect UHT treatment (137°C, 4 s) with less than 5% loss; however, in fermented matrices Lactobacillus delbrueckii subsp. bulgaricus enzymatically oxidizes the methylthiazole to 4-methyl-5-thiazolemethanol within 48 h at 4°C, generating a grassy, green-pepper defect. In stirred yogurt, sensory shelf life therefore contracts to 7 days unless aseptic post-fermentation dosing is implemented. Orthonasal threshold in paraffin oil is 0.04 ng/L air, determined by olfactometry following ISO 8586:2012 panel calibration. An operational incompatibility surfaces in nutraceutical formulations containing L-cysteine: high-shear rotor-stator mixing (>2,500 rpm) initiates a blue-green chromophore via thiazole-cysteine adduct polymerization, visible at ≥15 ppm thiazole in the premix. This chromophore cannot be bleached with standard peroxide washes and requires reformulation to eliminate the dual presence of free cysteine.

Coatings applied to extruded dry kibble for canine and feline nutrition exploit the meat-priming character of 4,5-dimethylthiazole at exceptionally low dosages—0.1–0.5 ppm by weight of the fat coating. Palatability performance is assessed by standard two-bowl preference tests under ASTM E1958-22, revealing an intake ratio increase of 15–22% over non-fortified control when the thiazole is co-dosed with disodium inosinate and disodium guanylate at a 1:1.2 molar ratio. Spray-drum coating lines operate at 60–80°C with atomized poultry fat; exceeding 80°C causes flash evaporation exceeding 30% of the thiazole charge. Pre-encapsulation in sodium tripolyphosphate-cross-linked gelatin (2.5% w/w of coating fat) reduces volatilization loss by 50%. Feline subjects display a bimodal hedonic curve: acceptance peaks at 0.3 ppm but transitions to active rejection at >5 ppm, characterized by video-ethogram markers of facial grooming and head shaking. Such trigeminal irritation disappears within 15 min but leads to long-term food aversion. Photolytic dimerization under warehouse lighting (UV 365 nm) is suppressed by storing the neat liquid in amber HDPE drums under 99.9% nitrogen blanketing; shelf life under these conditions is 24 months at 25°C.

What Limits Stereochemical Purity in Thiazole-Derived API Synthesis?

4,5-Dimethylthiazole serves as an alkylthiazole building block in the production of thiazole-2-acetic acid derivatives, intermediates for cephalosporin side chains and investigational non-steroidal anti-inflammatory candidates. A reliable entry route employs Vilsmeier–Haack formylation with POCl₃/DMF at −5 to 0°C to install the 2-formyl group; subsequent oxidation with KMnO₄ in aqueous NaOH at 5–10°C yields the acetic acid derivative. An alternative chloromethylation pathway uses paraformaldehyde and HCl (g) in 1,2-dichloroethane at 45°C to give 2-chloromethyl-4,5-dimethylthiazole, a versatile electrophile. Scaling in a 100 L Pfaudler glass-lined reactor with anchor agitation (60 rpm) reveals a yield-limiting exotherm: the formylation step must stay within ±2°C of the setpoint, otherwise over‑formylation at the 4-methyl position generates 4,5-dimethylthiazole-2,4-dicarbaldehyde (observed as an RRT 1.37 impurity on UPLC). To meet downstream GMP requirements, fractional distillation under 2.5 mbar with a boiling range of 92–94°C achieves >99.5% GC purity. Residual heavy metals are controlled by ICP-MS per Ph. Eur. 2.4.20, with palladium from optional coupling catalysis capped at <10 ppm. A strict incompatibility is noted with lithium diisopropylamide above −30°C: ring-opening to β-mercaptonitrile derivatives proceeds rapidly, reducing API yield to below 20%. Subsequent acid chloride generation requires anhydrous toluene and an N₂ pad to prevent hydrolysis back to the free acid, which precipitates in coupling solvents and halts the acylation step.

Agrochemical Scaffold Derivatization

The scaffold is an input to 5-functionalized thiazole intermediates that feed into thiazole-carboxamide fungicides and SDHI-modulating candidates. Radical bromination at the 2-methyl position uses N-bromosuccinimide with AIBN initiator in refluxing CCl₄ (77°C), achieving 85–90% conversion to 2-bromomethyl-4,5-dimethylthiazole. The subsequent Kornblum oxidation in dry DMSO with NaHCO₃ at 120°C forms the corresponding carbaldehyde; water content in the DMSO must remain below 0.1%, otherwise hydrolysis of the benzylic bromide diverts the stream to 2-hydroxymethyl by-product. Continuous flow processing in a Corning Advanced-Flow G1 reactor (12 min residence, 0.8 MPa back-pressure) lifts the isolated yield to 92%. Residual carbon tetrachloride is tightly controlled to ≤600 ppm under ICH Q3C Option 2. The aldehyde intermediate condenses with substituted anilines to yield Schiff bases that proceed into nematocidal screening under OECD 213 protocols. Pilot-plant aqueous effluent carries 15–20 g/L of succinimide side-products; Fenton oxidation (H₂O₂/Fe²⁺, pH 3.0, 60 min) achieves 97% TOC reduction before biotreatment. A site-specific note: the bromination step demands explosion-proof electrical classification (NEC Class I, Division 1) because of the CCl₄-AIBN reflux system, and dedicated vent scrubbers filled with 10% NaOH are installed to capture bromine vapors.

Low-moisture thermal process flavour generation bridges the thiazole into cysteine–xylose Maillard models for roasted meat topnotes. A validated precursor charge consists of 0.05–0.2% 4,5-dimethylthiazole based on total reactant dry weight, combined with L-cysteine hydrochloride monohydrate (2.5 parts), D-xylose (1.8 parts), and hydrolyzed vegetable protein (15 parts) in a propylene glycol–water vehicle (70:30 v/v). The reaction proceeds in a jacketed oil-heated vessel at 130°C for 2 h, with real-time FT-IR monitoring of the 1710 cm⁻¹ carbonyl stretch to determine endpoint when Strecker aldehyde concentration plateaus. The resulting flavour base retains 150–250 ppm residual 4,5-dimethylthiazole and generates 2-methyl-3-furanthiol and bis(2-methyl-3-furyl)disulfide, imparting juicy, bloody undertones to beef and chicken bouillons. Compliance with IOFI process flavouring guidelines requires absence of genotoxic burden, confirmed by Ames TA98 and TA100 assays (OECD 471) on the final diluted flavouring. An operational hazard: process pH drifting below 5.0 generates excessive free H₂S, which converts the thiazole irreversibly to thiazoline-2-thione (confirmed by HRMS m/z 144.0175), eroding active flavour intensity by 40%. Post-reaction nitrogen sparging at 50°C for 30 min strips residual H₂S and stabilizes the matrix for spray drying onto carriers such as maltodextrin DE 12.

Free Quote

Competitive 4.5-Methylthiazole prices that fit your budget—flexible terms and customized quotes for every order.

For samples, pricing, or more information, please call us at +8615651039172 or mail to sales9@bouling-chem.com.

We will respond to you as soon as possible.

Tel: +8615651039172

Email: sales9@bouling-chem.com

Get Free Quote of Bouling Chemical Co., Limited

Flexible payment, competitive price, premium service - Inquire now!

Get A Free Quote Now

Certification & Compliance

4.5-Methylthiazole is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales9@bouling-chem.com.

More Introduction

Addition of 4,5-dimethylthiazole to finished consumer product matrices requires careful solvent selection to mitigate flash-off during thermal processing. The compound demonstrates full miscibility in propylene glycol, triacetin, benzyl alcohol, and 95% ethanol but exhibits limited solubility in water (~0.8 g/L at 20°C). When integrated into extrusion-cooked pet food flavors, a pre-blended 10% (w/w) solution in triacetin is dosed via positive-displacement micro-pumps (e.g., Netzsch unit with 0.1 mL stroke volume) into a post-extrusion vacuum coater operating at −0.6 bar gauge, as atmospheric addition at die temperatures exceeding 110°C leads to volatilization losses exceeding 40% within 30 seconds. For liquid beverage compounding, stock solutions in ethanol at 0.1% are filter-sterilized (0.2 µm PP cartridge) and metered into the dosing tank during the final blending stage after pH adjustment, as the compound undergoes minor hydrolytic ring-opening at pH < 2.5 and temperatures above 85°C with a half-life of approximately 48 hours, based on accelerated stability testing at 40°C/75% RH per ICH Q1A(R2). A monocyclic alkylthiazole with methyl substitutions at the 4 and 5 ring positions, 4,5-dimethylthiazole (CAS 3581-91-7, FEMA 3274, JECFA 1036) presents as a pale yellow to amber mobile liquid exhibiting a sensory profile dominated by nutty, roasted, and cocoa-like backnotes with a subtle meaty undertone. The molecular formula is C₅H₇NS (MW 113.18). Industrial-grade material is typically supplied at a minimum purity of 98.5% as determined by flame ionization gas chromatography (FID-GC) using a polar stationary phase column, with the primary impurity being the 2-methyl isomer. In terms of sensory potency, the orthonasal detection threshold in water, determined via ASTM E679-19 forced-choice ascending concentration series, falls consistently within the range of 0.2–0.5 µg/L, significantly lower than that of 2-acetylthiazole (10 µg/L), enabling its use at sub-ppm levels in clear beverages without generating aroma imbalance. Solid-phase microextraction (SPME) headspace analysis above model beef broths shows a partition coefficient (K) favoring the vapor phase more strongly than 5-methylthiazole, contributing to pronounced impact in dry snack seasonings.

What Distinguishes 4,5-Dimethylthiazole from Other Alkylthiazoles in Flavor Formulation?

In contrast to 2-acetylthiazole (FEMA 3328), where the electron-withdrawing acetyl group at C-2 shifts the odor toward strong roasted, popcorn-like notes, or 2-isobutylthiazole (FEMA 3134), which imparts a green, tomato-leaf character, the 4,5-dimethyl variant lacks a substituent at the 2-position. This absence reduces steric hindrance and alters both vapor pressure and olfactory receptor affinity. The methyl groups at the 4 and 5 carbons donate electron density into the thiazole ring, raising the pKa of the nitrogen and moderating reactivity with electrophilic flavor precursors during Maillard reactions. The difference in substitution translates directly into processing utility: 4,5-dimethylthiazole remains stable through high-shear mixing at 5000 rpm in rotor-stator homogenizers for up to 45 minutes, whereas 2-acetylthiazole shows a 12% loss under identical conditions due to increased polarity and hydration. Furthermore, in top-note composition for poultry bouillon cubes, the compound creates a roasted–nutty bridge between savory base notes and the lighter sulfur notes of thiamine-derived 4-methyl-5-thiazoleethanol, a function that neither 2,4,5-trimethylthiazole (which pushes the character towards overly earthy) nor 2-acetylthiazole (which dominates with popcorn) can replicate.

Specifications and Purity Profiles for Industrial Compounding

The following table details the typical contractual release limits adopted by flavor house quality control laboratories, referencing the standards commonly cited on Certificates of Analysis accompanying drum and IBC shipments.

Parameter	Specification	Method / Standard
Purity (sum of isomers)	98.5% min	GC-FID (polar 30 m × 0.25 mm, 0.25 µm film)
Refractive index n²⁰/D	1.511–1.515	ISO 280:1998
Specific gravity d²⁰/20	1.045–1.055	ASTM D4052-22
Boiling point	163–166°C at 760 mmHg	Siwoloboff (capillary)
Water content	0.2% max	Karl Fischer (ASTM E203-16)
Refractive index stability after 12 months under N₂ headspace	< ±0.002 drift	In-house accelerated stability per ICH Q1E

All bulk deliveries must utilize epoxy-lined steel drums with a nitrogen headspace maintained at 0.2–0.5 bar overpressure. Storage at temperatures exceeding 35°C for prolonged periods (> 30 days) results in a detectable yellowing (APHA color shift from 50 to 150 Hazen units) without significant purity loss, though it signals the onset of oligomerization that can affect sensory character. Quantitative monitoring of 4,5-dimethylthiazole in finished dry soup mixes relies on stable isotope dilution gas chromatography–mass spectrometry (SIDA-GC-MS) with a limit of quantification (LOQ) of 0.01 µg/g when using a DB-WAX capillary column (60 m × 0.25 mm, 0.25 µm film). Recovery studies at spike levels of 0.1, 0.5, and 1.0 µg/g yielded mean recoveries of 92%–104% with RSD ≤ 7% (n=6), following a QuEChERS extraction protocol per AOAC 2007.01 modified with 0.1% formic acid in acetonitrile. This method circumvents the co-elution with 2-ethyl-4-methylthiazole that plagues standard non-polar systems, enabling accurate quantification for regulatory compliance checks within EU Regulation 1334/2008. During large-scale savory ingredient manufacture, inline near-infrared (NIR) probes installed in recirculation loops on 5,000 L compounding tanks provide a process analytical technology (PAT) approach to verify concentration uniformity at 0.05–0.5% addition levels within ±3% of target, referenced against the validated GC-MS method.

Why Does Headspace Stability Diverge in Low-pH Beverage Applications?

The thiazole ring’s susceptibility to acid-catalyzed degradation is influenced by the electron-donating methyl groups at C-4 and C-5. Comparative kinetic data generated in citrate-phosphate buffers show that at pH 3.0 and 60°C, 4,5-dimethylthiazole degrades at a rate constant of 1.2 × 10⁻³ h⁻¹, whereas 2,4,5-trimethylthiazole (JECFA 1037) degrades at 0.8 × 10⁻³ h⁻¹, attributable to steric protection at the 2-position. In still beverages stored under ambient shelf conditions (approximately 22°C), the olfactory impact loss is typically not organoleptically detectable before 6 months, but in products subjected to hot-fill (> 85°C) conditions, a cumulative flavor drop of 15–20% can occur by month 3. To counteract this, formulators have implemented encapsulation in octenylsuccinic acid (OSA)-modified starch (e.g., Ingredion Purity Gum 2000) at a flavor load of 20%, spray-dried with an inlet temperature of 180°C and outlet of 90°C, extending the detectable shelf life to 12 months in isotonic sports drinks. An operational boundary applies during cleaning-in-place (CIP) cycles: exposure of product-contact surfaces to 2% nitric acid solutions at 70°C for > 15 minutes can generate trace quantities of ring-opened thioamides, requiring a subsequent rinse with pH 7.0 demineralized water and a 0.1% bicarbonate rinse to neutralize residual acidity before the next production batch.

Comparative Performance Metrics for C3-C5 Alkylthiazoles

The table below aggregates published sensory and physical-property data derived from Fenaroli’s Handbook of Flavor Ingredients (6th ed.) and JECFA monographs, providing a side-by-side reference for substitution decisions in compounded flavor systems. Values represent the neat material unless a detection threshold is specified.

Property	4,5-Dimethylthiazole	2-Acetylthiazole	2,4,5-Trimethylthiazole	2-Isobutylthiazole
FEMA / JECFA	3274 / 1036	3328 / 1041	3225 / 1037	3134 / 1034
Odor character	Nutty, roasted cocoa, meaty	Strong roasted, popcorn, bread	Earthy, musty, slight cocoa	Green, tomato leaf, vine
Odor threshold in water (µg/L, orthonasal)	0.2–0.5	10	2.0	0.05
Boiling point (°C, 760 mmHg)	163–166	201–204	175–178	190–192
Typical use in savory (ppm as served)	0.5–5	0.2–3	0.5–10	0.01–0.1
Stability in aqueous acid (half-life at pH 3.0, 40°C)	~60 days	~90 days (Schiff base formation)	~75 days	~15 days

The divergence in acid stability at the bottom row is critical for cola-type beverages, where 2-isobutylthiazole requires complete microencapsulation while 4,5-dimethylthiazole can be used as an ethanol stock solution with only moderate top-note loss over the product’s intended consumption window.

Savory Reaction Flavor Bases: Optimizing Thermal Generation Pathways

In a pilot-scale Coperion ZSK 26 Mc¹⁸ twin-screw extruder (L/D 40), a reaction flavor base mimicking roasted beef is prepared from a dry blend of L-cysteine hydrochloride monohydrate (12 wt%), D-ribose (9 wt%), thiamine hydrochloride (3 wt%), and soy protein isolate (76 wt%), with water injection to 18% final moisture. The barrel temperature profile is set from 60°C (zone 1) to 145°C (zone 10) with a die temperature of 90°C. At a screw speed of 400 rpm and specific mechanical energy (SME) of 250 Wh/kg, the residence time is approximately 45 seconds. Under these conditions, the spontaneous generation of 4,5-dimethylthiazole via sugar degradation and cysteine Strecker pathways yields concentrations of 8–12 µg/g in the extrudate, as quantified by SIDA with deuterated 4,5-dimethylthiazole-d6 as internal standard. The reaction path depends critically on thiamine acting as a sulfur donor; omitting thiamine drops the yield to <1 µg/g and shifts the profile toward furfural-derived notes. To increase the ratio of roasted to meaty character, an additional post-extrusion spray of neat 4,5-dimethylthiazole at 0.02% (w/w) onto the hot extrudate increases the final concentration to 25 µg/g while avoiding the over-generation of 2-methyl-3-furanthiol, which otherwise contributes undesirable sulfury off-notes. Scale-up to production-size extruders (e.g., Clextral BC 72, L/D 36) requires compensation for the lower surface-to-volume ratio. Lowering the screw speed to 300 rpm and increasing the die temperature to 105°C maintains an equivalent thermal load, achieving an SME of 210 Wh/kg and a 4,5-dimethylthiazole in situ concentration of 9–11 µg/g while preserving the desired isomer profile. The hot extrudate is transferred directly to a Forberg F-500 fluidized-bed vacuum coater where the neat compound is atomized through a 0.5 mm nozzle under −0.5 bar gauge, achieving a coating uniformity of ±6% RSD across 100 kg batch sizes. Published data for this specific configuration is limited, but industrially validated starting-point formulations maintain a 4,5-dimethylthiazole to 2-acetylthiazole ratio of 3:1 to 5:1 for a balanced roasted-beef top note. Incompatibility considerations mandate that the flavor base not be blended with amine-rich lysine derivatives prior to extrusion, as premature Schiff base condensation reduces free cysteine availability and depresses 4,5-dimethylthiazole yield by up to 30%. Long-term stability of the dry extruded flavor base, stored at 25°C in multilayer aluminum-laminated pouches with a water vapor transmission rate below 0.1 g/m²/day, shows headspace retention of 90% of the target thiazole after 18 months, meeting the shelf-life requirements of dry soup and snack-seasoning manufacturers operating under ISO 22000-certified supply chains.