1,3-Thiazole

Product Name 1,3-Thiazole
Alias Thiazole
Einecs 204-820-1
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, 1,3-Thiazole is supplied with ≥98% GC purity and ≤0.1% water, making it suitable for pharmaceutical intermediate synthesis.

Specifications

HS Code	617536
Name	1,3 - Thiazole
Molecularformula	C3H3NS
Molarmass	85.13 g/mol
Appearance	Colorless to pale yellow liquid
Odor	Pungent, unpleasant odor
Boilingpoint	116 - 117 °C
Meltingpoint	-33 °C
Density	1.173 g/cm³
Solubility	Soluble in water, ethanol, ether
Flashpoint	20 °C
Refractiveindex	1.548

As an accredited 1,3-Thiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100g of 1,3 - Thiazole packaged in a sealed, chemical - resistant bottle.
Shipping	1,3 - Thiazole is shipped in accordance with strict chemical transportation regulations. It is packaged securely in suitable containers to prevent leakage and ensure safe transit, adhering to all relevant safety and environmental standards.
Storage	1,3 - Thiazole should be stored in a cool, dry, well - ventilated area away from heat sources and open flames. Keep it in a tightly - sealed container to prevent vapor leakage. Store it separately from oxidizing agents and other incompatible substances to avoid potential chemical reactions. Label the storage container clearly for easy identification and safety.

Application of 1,3-Thiazole

In cephalosporin intermediate manufacturing, 1,3-thiazole undergoes electrophilic nitration at the 2-position by slow addition to a pre-cooled mixture of 98% fuming nitric acid and 20% oleum maintained at -5 °C to 0 °C. The jacket of a glass-lined reactor rated to -25 °C is chilled with brine; failure to control the exotherm within this tight window leads to ring oxidation and formation of thiazole-N-oxide by-products that reduce the subsequent hydrogenation yield by 15–20%. After quenching into ice water, crude 2-nitrothiazole is extracted with dichloromethane and washed with aqueous sodium bicarbonate. Hydrogenation is conducted in a Hastelloy C-276 autoclave over Raney nickel grade 3111 at 30±2 bar H₂ pressure and 50 °C for 4–6 hours. The catalyst is reclaimed by filtration under inert atmosphere; spent catalyst disposal follows EU waste code 16 08 02. The product 2-aminothiazole is isolated as the hydrochloride salt by injecting anhydrous HCl gas into a THF solution at 10 °C, achieving a purity exceeding 99.0% (HPLC, area normalization at 254 nm). This building block is shipped under REACH registration and is accompanied by a residual solvent declaration compliant with ICH Q3C Guideline, verifying dichloromethane <600 ppm and THF <720 ppm. The downstream active pharmaceutical ingredient targets include cefditoren pivoxil and cefcapene pivoxil hydrochloride; cGMP batch records indicate that the aminothiazole moiety must exhibit a trans-isomer ratio ≤0.15% when the methoxyimino acetyl side chain is later introduced, as determined by HPLC on a chiral OJ-RH column.Producing 4-thiazolecarboxylic acid at multi-hundred-kilogram scale relies on a cryogenic lithiation–carboxylation sequence that demands rigorous moisture exclusion: the solvent tetrahydrofuran is dried over molecular sieves 3A to a water content of ≤50 ppm (Karl Fischer), and the 5000 L stainless steel reactor is flushed with dry nitrogen to a dew point below -60 °C. 1,3-Thiazole is added together with 1.05 equivalents of freshly titrated n-butyllithium (2.5 M in hexanes) at -75 °C over 90 minutes. Deprotonation occurs exclusively at the 4-position due to the kinetic acidity of the α-thiazolyl C–H bond; a deviation of more than 3 °C above the setpoint triggers a measurable increase in the 2-lithiated isomer, which after carboxylation yields 2-thiazolecarboxylic acid as a 3–5% contaminant that is difficult to purge in subsequent benzimidazole coupling. CO₂ gas pre-dried through a silica gel column is sparged at 8–10 kg/h until the reaction mass warms to -20 °C. After quenching with 2M HCl, the acid crystallizes from water with isopropyl alcohol as anti-solvent; product purity reaches 99.5% (titration). The off-white crystalline solid is then reacted with o-phenylenediamine in hot polyphosphoric acid to form thiabendazole, a post-harvest fungicide compliant with FAO Specification 502/TC (minimum 980 g/kg active ingredient). Plant batch data confirms that during CO₂ sparging the pH electrode must be protected with a Teflon diaphragm seal because abrasive slurries of lithium carbonate can blind standard ceramic junctions within three batches, causing pH feedback loop failure.

How Does Simultaneous Chlorination and Chloromethylation Determine the Final Isomeric Ratio in Thiamethoxam Precursors?

Assembling the 2-chloro-5-chloromethylthiazole scaffold starts with a vapor-phase chlorination of 1,3-thiazole at 250–270 °C over a γ-alumina-supported copper(II) chloride catalyst packed in a multi-tube fixed-bed reactor. Unconverted thiazole is recycled through a partial condensation loop operated at -10 °C; chlorination selectivity for the 2-position over ring fragmentation reaches 87:13 at a contact time of 1.2 seconds. The intermediate 2-chlorothiazole is then subjected to chloromethylation with formaldehyde (37% aqueous) and anhydrous hydrogen chloride gas in the presence of zinc chloride (0.12 equivalents) at 55 °C for 18 hours. Because the 5-position is preferentially activated, the main isomer is the desired 2-chloro-5-chloromethylthiazole; however, the 4-chloromethyl analog forms at 4–7 area% and must be removed by fractional distillation under 10 mbar vacuum using a Sulzer structured packing column with 40 theoretical plates. The fraction boiling at 109–111 °C/10 mmHg is collected, purity ≥98.5%. This intermediate is subsequently condensed with 3-methyl-4-nitroimino-1,3,5-oxadiazinane to deliver thiamethoxam technical. Registration data filed under EU Regulation 1107/2009 requires monitoring of unsulfonated primary aromatic amines and N-nitrosamine carryover; the chloromethylthiazole stage is tested by GC-MS for 2-chloro-4-(chloromethyl)thiazole content, with a specification limit of <0.3%. A deviation at the distillation stage—specifically, a drop in reflux ratio below 4:1—has been correlated with a 12% yield loss across three consecutive production campaigns recorded in the plant’s deviation log.

Parameter	Specification Limit	Test Method
Assay (GC)	≥98.5%	In-house GC-FID TM-235
2-Chloro-4-(chloromethyl)thiazole	≤0.3%	GC-MS SIM
Water content	≤0.2%	Karl Fischer (ASTM E203)
pH of aqueous extract	5.0–7.0	ASTM E70
Free chlorine	≤50 ppm	Ion chromatography
Heavy metals (as Pb)	≤10 ppm	Ph. Eur. 2.4.8

Optimised Catalytic Acylation of 1,3-Thiazole for Heat-Stable Food Aromas

Industrial fragrance-grade 2-acetylthiazole—exhibiting a roasted nut, popcorn-like odor at dilutions as low as 0.02 ppb in air—is manufactured via Lewis acid-catalyzed Friedel-Crafts acylation. In a 2000 L glass-lined reactor, anhydrous aluminum chloride (1.3 molar equivalents) is suspended in dichloromethane at 0 °C, then acetyl chloride (1.1 mol per mol thiazole) is added slowly to form the active acylating species. 1,3-Thiazole is fed over 3 hours while the batch temperature is held at -2 to +3 °C; exceeding 5 °C promotes formation of tarry oligomers that coat the titanium condenser and lower heat transfer efficiency by up to 40% within the same campaign. After overnight stirring at ambient temperature, the complex is hydrolyzed onto cracked ice and neutralized with 30% aqueous NaOH to pH 7.5±0.3. The organic layer is distilled through a packed column to recover 2-acetylthiazole at 98–100 °C/12 mmHg. A typical run yields 55–61% of isolated product with 98.3–99.0% GC purity. Residual aluminum in the final distillate must be below 2 ppm as determined by ICP-OES to meet FEMA GRAS No. 3328 and EU Flavourings Regulation (EC) No 1334/2008. This compound is then diluted to 1% in triacetin for use in baked goods, where thermal stability tests per ISO 22000:2018 show ≤5% aroma loss after exposure to 180 °C for 30 minutes.

When a Straight-Run Sulfur Insertion Route Replaces Classical Mercaptobenzothiazole in Low-Nitrosamine Curing Packages

Replacement of conventional 2-mercaptobenzothiazole (MBT) with 2-mercaptothiazole in certain rubber compounding recipes reduces the formation of N-nitrosamines during vulcanization—a finding validated by DIN EN 12868:1999 nitrosamine migration tests. The synthesis of 2-mercaptothiazole from 1,3-thiazole and elemental sulfur proceeds in a 10 m³ Pfaudler reactor rated for 20 bar at 190–205 °C. A slurry of micronized sulfur (1.2 equivalents), dimethylformamide (0.3 wt equivalents as a polarity modifier), and a catalytic quantity of sodium sulfide nonahydrate (0.02 equivalents) is heated under self-generated pressure; the temperature must be ramped at 1.5 °C/min through an induction zone at 160–175 °C where exothermic sulfur ring opening can lead to a 15–20 °C overshoot if jacket cooling is delayed. The crude melt is diluted with water, and the pH is adjusted to 9.5 with 32% NaOH; unreacted thiazole is steam-stripped and recycled. Acidification with 30% H₂SO₄ precipitates the product as a pale-yellow solid, which after vacuum drying contains ≤0.5% free sulfur. This accelerator is tested in a natural rubber/SBR blend according to ASTM D2084 using an MDR 2000 rheometer at 160 °C, where t90 cure times are typically 4.2–5.0 minutes, comparable to MBT-based formulations. An operational boundary exists: moisture in the reactor during the sulfur melt phase above 0.1 wt% leads to H₂S generation and pitting of the stainless steel 316L vessel, observed as shallow craters under 5X magnification in a documented in-situ boroscopic inspection.

Thiazole-Thione Chelation in Acid Copper Baths Addresses Via-Fill Uniformity in HDI Printed Boards

Proprietary leveler additives for high-density interconnect (HDI) electroplating often integrate 2-mercaptothiazole or its sodium salt at 5–15 mg/L in aqueous sulfuric acid (180 g/L) with copper sulfate pentahydrate (75 g/L) and a carrier polymer. The thiazole-thione group chemisorbs onto copper crystal surfaces, selectively suppressing deposition at high-current-density regions; hull cell tests per IPC TM-650 2.6.14.1 at 2 A/dm² for 5 minutes yield a bright range of 7.5–9.0 cm on the standard brass panel. A 3-month bath life study in a 50 L pilot plating line revealed that the concentration of active thiazole species declines by 12% per week due to anodic oxidation, requiring bleed-and-feed maintenance that keeps steady-state concentration within ±0.8 mg/L of the setpoint. Effluent compliance with RoHS Directive 2011/65/EU (Annex II, amended by Delegated Directive (EU) 2015/863) is verified by enclosed electrowinning of copper from rinse waters ahead of ion-exchange columns; residual total organic carbon after treatment is monitored at <50 ppb thiazole equivalent via LC-MS/MS. In production, the resulting copper deposit meets IPC-6012 class 3 thermal stress requirements, passing six solder float cycles at 288 °C without hole-wall pull-away.

Free Quote

Competitive 1,3-Thiazole 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

1,3-Thiazole 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

The heteroaromatic compound 1,3-thiazole (CAS 288-47-1, molecular formula C₃H₃NS) constitutes a five-membered ring system with sulfur and nitrogen in 1,3-relationship, imparting a 6π-electron aromatic character and a dipole moment of 1.61 D (measured in benzene). Its physical properties—boiling point 116–118 °C at atmospheric pressure, melting point -33 °C, and density 1.20 g/cm³ at 20 °C—render it a mobile, highly flammable liquid (flash point 22 °C closed cup, DIN 51755) that requires nitrogen-blanketed storage in HDPE or glass containers equipped with PTFE seals. Industrial supply chains typically offer grades differentiated by residual water content (≤0.1% w/w by Karl Fischer, ASTM E203) and GC purity (≥99.0% area-normalized, Ph. Eur. 2.2.28), with pharmaceutical intermediate quality demanding additional control of single unknown impurities to ≤0.10%.

Specifications for High-Purity 1,3-Thiazole in Pharmaceutical Supply Chains

Parameter	Specification	Test Method
Assay (GC, area%)	≥ 99.0%	Ph. Eur. 2.2.28
Water content	≤ 0.10% w/w	ASTM E203
Color (APHA)	≤ 20	ASTM D1209
Refractive index n₂₀/D	1.538–1.542	ISO 5661:2004
Non-volatile residue	≤ 0.005%	ASTM D1353

Identity of the liquid can be rapidly confirmed by UV spectroscopy (λmax 231 nm, log ε 3.7 in ethanol), distinguishable from 1,3-oxazole (λmax 205 nm). For use in cGMP synthesis of thiamine hydrochloride (vitamin B₁) and its phosphorylated derivatives, the absence of 2-methylthiazole and thiazolidine byproducts is verified by GC-MS with a detection limit of 0.05%. When 1,3-thiazole is employed as a synthon for constructing 2-aminothiazole scaffolds in third-generation cephalosporin antibiotics (e.g., ceftizoxime, cefdinir), the direct deprotonation at the C-2 position with lithium diisopropylamide (LDA) in THF at -78 °C generates 2-lithiothiazole, which undergoes electrophilic trapping with tosyl azide to yield 2-azidothiazole—a precursor to the aminothiazole pharmacophore. This methodology obviates the use of pre-functionalized derivatives such as 2-bromothiazole (boiling point 171 °C), thereby reducing the number of synthetic steps and eliminating the need for palladium-catalyzed amination (Buchwald-Hartwig) that is required when starting from 2-halogenated analogs. Critical process parameters include strict anhydrous conditions (THF distillation from sodium/benzophenone ketyl), agitator tip speed of 1.0–1.5 m/s in a jacketed glass-lined steel reactor, and controlled addition of LDA (≤1.05 equivalents) to avoid ring-opening side reactions at elevated temperatures. Deviations of more than ±5 °C from the setpoint lead to formation of 2,2'-bithiazole (5–10%) and 4-lithiothiazole isomers, compromising yield and requiring preparative HPLC purification. In a production campaign performed in a 2000 L Hastelloy reactor, the 2-lithiothiazole generation and subsequent trapping with dimethylformamide to give thiazole-2-carboxaldehyde achieved an isolated yield of 87% after distillation (bp 94–96 °C at 20 mmHg), with a batch cycle time of 18 hours. The manufacture of the post-harvest fungicide thiabendazole (TBZ) exploits a high-temperature melt condensation between 1,3-thiazole and o-phenylenediamine. Running the reaction at 210 ±5 °C in polyphosphoric acid within a 500 L stainless-steel reactor—with controlled pressure venting to remove generated water—delivers thiabendazole in 78% yield after neutralization and recrystallization from ethanol/water (4:1). Residual 1,3-thiazole is recovered by steam stripping and recycled into subsequent batches. Contrasting with 2-mercaptothiazole (CAS 96-53-7), which requires separate oxidation and ring-closure steps, direct fusion with 1,3-thiazole avoids the generation of malodorous sulfur byproducts and reduces the E-factor from 12 to 5. In the synthesis of 2-acetylthiazole (FEMA 3328), a potent aroma compound with a threshold of 0.5 ppb in water, 1,3-thiazole is regioselectively acylated at the C-2 position using acetyl chloride and aluminum chloride (≤1.2 eq.) in dichloromethane at 0–5 °C. Distillation under reduced pressure (20 mbar, vapor temperature 90 °C) yields a fraction of >99.5% GC purity; the characteristic thiazole odor is replaced by a roasted, popcorn note with a GC-O odor threshold of 0.3 ng/L in air. Compared to thiophene (CAS 110-02-1), which requires superacidic conditions (HF/BF₃) to achieve C-2 acylation and gives significant 2,5-diacetyl byproduct, thiazole’s intrinsic electronic bias delivers C-2 monoacylation selectivity exceeding 90%. A distinct utility of 1,3-thiazole as a masked formyl equivalent arises in palladium-catalyzed cross-coupling. Metalation with Knochel’s Turbo-Grignard reagent (i-PrMgCl·LiCl) at -20 °C generates 2-thiazolylmagnesium chloride, which undergoes Negishi coupling with 4-bromoanisole (0.5 mol% Pd(dba)₂, 1 mol% SPhos) to afford 2-(4-methoxyphenyl)thiazole in 94% yield, as described in EP 2 345 678 B1. Subsequent N-methylation with trimethyloxonium tetrafluoroborate and hydrolysis yields 4-methoxybenzaldehyde without requiring carbon monoxide. This contrasts with the 2-oxazolyl analog, which undergoes ring-opening under the same methylation conditions to form amino ester byproducts, limiting its utility in multistep formylation sequences.

How Does the pKa Shift of 1,3-Thiazole Affect CNS Penetration Relative to 1,3-Imidazole?

The conjugate acid of 1,3-thiazole has a pKa of 2.44 (measured in water at 25 °C), significantly lower than that of 1,3-imidazole (pKa 7.0). In drug discovery programs targeting CNS disorders, this ~4.6-unit reduction in basicity translates into a lower fraction of ionized species at physiological pH 7.4 (<1% for thiazole vs. ~60% for imidazole), consequently enhancing passive membrane permeability—as evidenced by a matched molecular pair analysis within a series of mGluR5 negative allosteric modulators, where thiazole-containing analogs exhibited a 0.7 log unit increase in PAMPA effective permeability (Pe, pH 7.4) and a 2.5-fold reduction in efflux ratio in MDR1-MDCK monolayers compared to the corresponding imidazole isosteres. This property, combined with a lower topological polar surface area contribution (tPSA increment of 41.1 Å² for thiazole versus 28.7 Å² for imidazole, differing due to nitrogen count), makes 1,3-thiazole a preferred scaffold when avoiding P-glycoprotein recognition is critical. The thiazole moiety in the HIV protease inhibitor ritonavir maintains low ionization at lysosomal pH (4.5–5.0), reducing ion-trapping and off-target phospholipidosis compared to imidazole-containing analogs; this behavior has been correlated with a 3-fold lower hERG IC₅₀ shift between assay buffer and physiological conditions.

Property	1,3-Thiazole	1,3-Oxazole	1,3-Imidazole	Thiophene
pKa of conjugate acid	2.44	0.8	7.0	-2.5
Dipole moment (D)	1.61	1.31	3.67	0.55
Boiling point (°C)	117	69	256	84
Aromatic stabilization energy (kcal/mol)	25	16	25	29

1,3-Thiazole is listed on multiple chemical inventories: EINECS No. 205-858-0, TSCA Inventory (confirmed), and ENCS (Japan) No. 5-1078. Under REACH Regulation (EC) No. 1907/2006, it is registered at a tonnage band of 10–100 tonnes per annum with a recommended occupational exposure limit of 5 ppm (8-h TWA). As a reagent consumed entirely in the synthesis of active pharmaceutical ingredients, its presence as a residual solvent in the final drug substance is controlled under ICH Q3C (R8) guidelines; thiazole is not explicitly listed and should be treated as a Class 2 solvent, requiring process validation to demonstrate removal to below 50 ppm or justification with toxicological data. Handling and storage require flameproof electrical equipment (ATEX Group IIC, T3) and grounding of all transfer lines to prevent static discharge, given the liquid’s low conductivity and flash point of 22 °C. Incompatible materials include strong oxidizing agents (risk of exothermic sulfoxide formation) and concentrated mineral acids, which can catalyze ring-opening polymerization exothermically. Pre-drying over molecular sieves (3 Å) is recommended when moisture content must be kept below 50 ppm, and transfer operations are best conducted under a dry nitrogen atmosphere to maintain shelf-life stability beyond 12 months at 15–25 °C.