2-(Hydroxymethyl)-1,3-Thiazole 97%
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HS Code |
504882 |
| Name | 2-(Hydroxymethyl)-1,3-Thiazole 97% |
| Chemical Formula | C4H5NOS |
| Molecular Weight | 115.15 |
| Appearance | Typically a colorless to light yellow liquid or solid (description may vary) |
| Boiling Point | Data may vary depending on purity and conditions |
| Melting Point | Data may vary depending on purity and conditions |
| Solubility | Solubility characteristics in common solvents like water, ethanol, etc. would need further data |
| Density | Data may vary depending on purity and conditions |
| Flash Point | Data may vary depending on purity and conditions |
| Stability | Should be stored under appropriate conditions to maintain stability, may react with certain substances |
As an accredited 2-(Hydroxymethyl)-1,3-Thiazole 97% factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 500g of 97% 2-(Hydroxymethyl)-1,3-Thiazole in sealed chemical - grade packaging. |
| Shipping | 2-(Hydroxymethyl)-1,3-Thiazole 97% is shipped in properly sealed, chemical - resistant containers. Special care is taken to ensure stability during transit, adhering to all relevant hazardous material shipping regulations. |
| Storage | Store “2-(Hydroxymethyl)-1,3-Thiazole 97%” in a cool, dry place away from heat and direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contamination. Store it separately from oxidizing agents and incompatible substances to avoid potential reactions. Follow all safety guidelines during storage. |
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2-(Hydroxymethyl)-1,3-thiazole 97% is introduced into a GMP-compliant reactor train as the heterocyclic donor for 2-(1,3-thiazol-4-yl)benzimidazole synthesis. The process demands strict oxidation state control at the C2 carbon: the hydroxymethyl group is converted to a carboxaldehyde via a two-phase TEMPO/NaOCl catalytic system at pH 9.0–9.5 and a jacket temperature maintained at 5–8 °C. The molar ratio of substrate to primary oxidant is kept at 1:1.05 to minimize over-oxidation to the carboxylic acid—a side product that reduces coupling efficiency with o-phenylenediamine in the next step by 12–18% if present above 0.8 wt%. The aldehyde intermediate is not isolated; it is directly condensed with diamine in methanolic hydrogen chloride at reflux, generating the benzimidazole ring in a single telescoped operation. Regulatory oversight applies from the point at which the thiazole alcohol is designated as the GMP starting material per ICH Q7 Q&A decisions. Residual solvent analysis of the isolated thiabendazole must meet Ph. Eur. 5.4 requirements, with a methanol limit of 3,000 ppm and acetonitrile below 410 ppm, verified by headspace GC-FID following Ph. Eur. 2.4.24. The final active pharmaceutical ingredient is micronized to a particle size D90 ≤ 15 µm and formulated as a suspension concentrate for post-harvest citrus treatment under FDA 21 CFR 556.730 tolerance. When Thionyl Chloride Replaces Aqueous HCl, an Exothermic Route to 2-(Chloromethyl)thiazole OpensThe single largest-volume demand for 2-(hydroxymethyl)-1,3-thiazole 97% originates from the neonicotinoid insecticide supply chain. Conversion to 2-(chloromethyl)thiazole is performed by slow addition of thionyl chloride to a dried dichloromethane or toluene solution of the alcohol maintained under a nitrogen sweep. The molar feed ratio of SOCl₂ to substrate is held between 1.2:1 and 1.35:1; the excess serves to scavenge residual water but must be limited because it also generates bis(chlorinated) thiocyanate impurities when local concentration spikes exceed 1.5 M. Reaction enthalpy reaches ‒180 to ‒210 kJ/mol, necessitating a half-pipe jacketed glass-lined reactor with brine circulation capable of maintaining the mass temperature at 0–5 °C during the 1.5–2.0 h addition. Any excursion above 12 °C initiates a runaway side pathway that oligomerizes the thiazole ring via ring-opening at the sulfur atom, discolouring the batch and dropping yield below 72%. The crude chloromethylthiazole is distilled under reduced pressure (8–12 mbar, head temperature 78–82 °C) and must exhibit a Karl Fischer moisture content below 500 ppm before entering the downstream coupling with N-methyl-N′-nitro-N-nitrosoguanidine-type intermediates. Agrochemical specifications invoke CIPAC MT 18 and MT 39 protocols for purity assignment. The final formulated insecticides—thiamethoxam and clothianidin—are registered under EU Reg. 1107/2009, requiring a five-batch analysis of the intermediate to demonstrate the absence of hydrazine-derived mutagenic impurities at LOD 0.01%. Can a Thiazole Alcohol Deliver Grilled-Meat Notes Without Browning Reactions?In savory flavour delivery systems, 2-(hydroxymethyl)-1,3-thiazole 97% functions not as a volatile aroma impact molecule but as a glycosidase-labile precursor. When the hydroxyl group is conjugated with a β-glucopyranosyl moiety via a Koenigs–Knorr-type condensation, the resulting glucoside remains odourless in aqueous phase and withstands UHT processing at 135 °C for 4 s with less than 2% premature hydrolysis. Upon contact with human salivary α-glucosidase or the cell-bound β-glucosidases of Aspergillus oryzae in a fermented coating, the conjugate liberates the free thiazole alcohol, which rapidly equilibrates to a mixture of aldehyde, alcohol, and imine forms when amino acid sources are present, generating a volatile profile that reproduces the 2-acetylthiazole character without thermal Maillard input. Use levels in finished dry seasoning blends range from 0.05 ppm to 1.2 ppm expressed as free alcohol equivalent. Toxicological clearance is provided under FEMA GRAS 26 for related thiazole esters; the alcohol itself requires a JECFA intake evaluation and falls under EU flavouring substance category FL 15.001. Specification sheets for flavour-house procurement stipulate a benzothiazole impurity cap of 100 µg/kg because even trace carryover shifts the profile toward rubbery notes, detectable by a trained GC-sniffing panel at an odour threshold of 0.8 ng/L air. The conjugate is typically solubilized in triacetin before blending with maltodextrin carriers and co-spray-drying at an inlet temperature of 170 °C, yielding a free-flowing powder with a water activity below 0.25 for storage stability. Oxidation of the hydroxymethyl substituent to a formyl group is the initial step in preparing thiazole-2-carboxaldehyde—a versatile precursor to Schiff-base ligands, thiazole-2-oxime quaternary ammonium reactivators, and heterocyclic fused-ring systems used in early-stage drug discovery libraries. A pyridinium chlorochromate slurry in dichloromethane containing 3 Å molecular sieves achieves 89–93% conversion within 4 h at 22–25 °C when the oxidant is loaded at 1.5 molar equivalents. The sieves are mandatory; the exothermic hydration of PCC byproduct chromium species otherwise hydrolyses the aldehyde product back to the alcohol, erasing yield. Direct filtration through a silica plug and vacuum distillation (2 mbar, overhead 52–55 °C) deliver thiazole-2-carboxaldehyde at 98.5% GC purity, which can be further upgraded via NaHSO₃ adduct purification to 99.9% when required for organocatalytic asymmetric synthesis. Downstream, the aldehyde reacts under mild conditions with primary amines to form imine-linked covalent organic framework (COF) monomers or is converted to the corresponding oxime with hydroxylamine hydrochloride in buffered ethanol. A minor but commercially significant outlet is the Mannich condensation with formaldehyde and dimethylamine hydrochloride to install an N,N-dimethylaminomethyl group at the C5 ring position, generating intermediates for Mannich-base corrosion inhibitors. The starting 2-(hydroxymethyl)-1,3-thiazole 97% must be accompanied by a certificate of analysis reporting the aldehyde content already present (typically 0.3–0.7%) because this pre-existing impurity inflates titration-based aldehyde assay results and complicates endpoint control in subsequent cGMP syntheses. Published data for the specific oxime-to-quaternary-ammonium reactivator intermediates in nerve-agent countermeasure research remain limited, with most DoD-funded studies using internal purity standards not publicly disclosed. Carbon Steel Acidizing Inhibitor Formulations and Weight-Loss Coupon EvidenceDuring matrix acidizing of carbonate reservoirs with 15 wt% HCl at bottomhole temperatures of 85–105 °C, 2-(hydroxymethyl)-1,3-thiazole 97% is blended as a synergist at 0.3–1.0 vol% of the total acidizing package. It functions by co-adsorbing with propargyl alcohol or cinnamaldehyde-based primary inhibitors onto the cathodic sites of N-80 and L-80 tubing steel. The hydroxyl group improves hydrogen-bond anchoring to the partially hydrated iron oxide layer, reducing the concentration of the primary inhibitor required to achieve less than 0.05 lb/ft² weight loss in a 6 h ASTM G31-72 immersion test. Without the thiazole synergist, identical protection demands a primary inhibitor loading 1.8–2.2 times higher—a cost difference that becomes decisive in multi-thousand-barrel acid jobs. A typical pre-blend ratio is propargyl alcohol: thiazole alcohol 4:1 by weight, combined in a mutual solvent (methanol, isopropanol, or ethylene glycol monobutyl ether) and then metered into the acid stream via a positive-displacement pump at the suction side of the high-pressure triplex. The formulation must remain clear and free of phase separation after 72 h static storage at -5 °C, a requirement checked per ASTM D97 pour-point methodology. An operational boundary exists: the thiazole compound undergoes irreversible ring sulfonation and loss of inhibitor activity when the acid temperature exceeds 120 °C for more than 30 min, as confirmed by electrochemical impedance spectroscopy in a rotating cylinder electrode (RCE) setup. Field return-fluid analysis using ICP-OES quantifies iron from dissolved tubulars; the thiazole-synergized systems consistently keep dissolved iron below 1,200 ppm, whereas uninhibited controls reach 12,000–15,000 ppm within the same time window.
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2-(Hydroxymethyl)-1,3-thiazole (IUPAC: 1,3-thiazol-2-ylmethanol, CAS 19311-27-2) is supplied as a colourless to pale yellow liquid with a characteristic pyridine-like odour, solidifying near 0–5 °C and boiling at 114–116 °C at 2.4 kPa. The product lot typically assays at 97.0% minimum by GC (FID) on a polar column, with balance comprising homologous alcohols, water, and trace aldehydes. Unopened ampoules loaded under argon retain this purity envelope for 12 months when kept at 2–8 °C in light-resistant packaging. The hydroxymethyl appendage attached to the C2 position of the electron-deficient thiazole ring imparts a polarity (log P ~0.5) and hydrogen-bonding capacity distinct from halogenated, methylated, or aminated analogues, making this intermediate a linchpin in convergent assembly of pharmacophore-bearing heterocycles.
Direct reactivity benchmarking against reference building blocks clarifies the niche of the hydroxymethyl variant. 2-Methylthiazole (CAS 3581-87-1) provides C–H acidity at the methyl position yet requires harsh oxidants or halogenation to engage in cross-coupling; the sp³-hybridized carbon demands radical-mediated or lithiation protocols that narrow solvent compatibility. 2-Bromothiazole (CAS 3034-53-5) is a robust electrophile for metal-catalysed transformations, but its cost per mole is typically 3–5× higher and its volatility complicates accurate dispensing in automated parallel synthesis platforms. The amine counterpart, 2-aminothiazole (CAS 96-50-4), dominates heterocyclic condensation reactions yet introduces a nucleophilic nitrogen that can quench electrophilic reagents or coordinate transition metals undesirably downstream. By contrast, the primary alcohol of 2-(hydroxymethyl)-1,3-thiazole can be activated selectively—via mesylation, tosylation, or conversion to the chloride using thionyl chloride in toluene at 0–5 °C—without perturbing the thiazole ring. The resulting 2-chloromethylthiazole intermediate participates in Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig couplings under standard catalytic conditions (e.g., Pd(PPh3)4 2 mol%, K2CO3, dioxane/water 4:1 v/v, 85 °C), while the intact hydroxyl can serve as a hydrogen-bond donor in target engagement assays. Oxidation to 2-thiazolecarboxaldehyde (melting point 41–43 °C) with Dess–Martin periodinane in dichloromethane at 20–25 °C proceeds quantitatively, enabling Schiff-base formation and reductive amination sequences pivotal in lead-optimisation chemistry.
Storage under inert atmosphere at 2–8 °C in amber borosilicate bottles with PTFE-lined caps prevents discolouration and limits moisture ingress to below 0.1% w/w over 12 months.
Crude reaction liquors from the sodium borohydride reduction route contain variable amounts of water, 2-methylthiazole, and high-boiling oligomeric species. Pilot-plant purification at scales exceeding 50 kg is executed on a wiped-film evaporator (heat-transfer area 0.06 m², L/D ratio 5, jacket temperature 100 °C) operating at 2.0–3.0 mbar absolute pressure. Under these conditions, the mid-boiling cut distils at a vapour temperature of 68–72 °C, yielding material of 98.5% GC purity. Differential scanning calorimetry (DSC) performed per ASTM E537-20 on a representative crude aliquot (aluminium pan, pierced lid, 5 °C/min ramp) displays a mild exotherm onset at 165 °C with a peak at 225 °C, attributed to condensative dehydration of the alcohol group to form 2-methylenethiazoline and polyethers. To maintain a ΔTadiabatic safety margin, bulk distillation temperatures are capped at 110 °C. Processing delays that expose the hot residue to air raise the peroxide value (tested by iodometric titration per ASTM E298-17a) and must be avoided; nitrogen-purged receivers and a cold trap at -78 °C are mandatory. Batch-to-batch variation in the overhead colour (APHA shift from <50 to >150 hue) has been traced to iron leachate from stainless-steel condenser tubing—remediation by electropolishing the wetted surfaces restores colour specification.
Release testing combines gas chromatography, coulometric Karl Fischer titration, and headspace analysis. A non-polar fused-silica capillary column (HP-5, 30 m × 0.32 mm, 0.25 µm film thickness) with flame ionisation detection resolves the main alcohol peak (retention index ~1200) from 2-thiazolecarboxaldehyde (retention index ~1050) and the 4-hydroxymethyl isomer (retention index ~1250). The limit of quantitation for 2-methylthiazole is set at 0.05%. Water content determined by coulometric KF (ASTM E203-23) is routinely 0.02–0.08% immediately after distillation; exposure to ambient air (60% RH) for 30 min elevates the value to 0.4–0.6%, confirming the necessity of septum-sealed handling. Residual solvents—tetrahydrofuran, methanol, and toluene—are quantified by static headspace GC-MS against an external standard matrix-matched to the product. Individual solvent limits are aligned with USP <467> Option 1 residual solvent classes, with methanol not exceeding 3000 ppm and toluene below 890 ppm. A certificate of analysis (CoA) for each lot includes these three orthogonal data sets, plus visual appearance and specific gravity at 20 °C (1.210–1.225 g/cm³).
The following table documents impurity profiles collected from two prevalent synthetic routes: Route A — sodium borohydride reduction of 2-thiazolecarboxaldehyde in methanol at 0 °C, followed by aqueous quench and continuous extraction; Route B — acid-catalysed hydroxymethylation of thiazole with paraformaldehyde in aqueous HCl at 80 °C for 18 h. The data represent mean values from five consecutive pilot batches per route.
| Impurity | CAS No. | Route A (% area) | Route B (% area) | Analytical Method |
|---|---|---|---|---|
| 2-Thiazolecarboxaldehyde | 10200-59-6 | 0.12 ± 0.03 | 0.85 ± 0.15 | GC-FID |
| 2-Methylthiazole | 3581-87-1 | 0.08 ± 0.02 | 1.40 ± 0.22 | GC-FID |
| 4-(Hydroxymethyl)-1,3-thiazole | 105915-62-2 | 0.05 ± 0.01 | 2.10 ± 0.35 | GC-FID (chiral column available) |
| Thiazole | 288-47-1 | 0.01 ± 0.01 | 0.50 ± 0.10 | Headspace GC-MS |
| Water (Karl Fischer) | — | 0.04 ± 0.01 | 0.18 ± 0.05 | Coulometry (ASTM E203) |
| Total heavy unknowns (RRT >1.5) | — | 0.25 ± 0.05 | 0.90 ± 0.20 | GC-FID (area%) |
Route A delivers superior selectivity owing to the crystalline starting aldehyde’s purity and the low-temperature reduction regime. Route B generates regioisomeric hydroxymethyl species because thiazole can ring-open under the strongly acidic conditions, leading to recombination that places the electrophilic carbon at the 4- or 5- positions. For rigorous structure–activity relationship studies, where isomeric contamination must remain below 0.1%, only Route A-derived material is recommended.
In multi-kilogram synthesis of N-heterocyclic carbene (NHC) precursors, the alcohol is oxidised in situ with 1.1 eq. Dess–Martin periodinane suspended in wet dichloromethane (0.1 M water added) at 20 °C. The resultant 2-thiazolecarboxaldehyde is filtered through a silica plug and condensed with a chiral amino alcohol (e.g., (S)-tert-leucinol) in toluene at reflux with a Dean–Stark trap. The oxazoline ring closes within 6–8 h; however, the water generated during imine formation must be removed to <100 ppm to achieve yields above 80%. Molecular sieves 3 Å (activated at 300 °C) are introduced directly into the reaction vessel. Published data for this specific configuration is limited to laboratory-bench studies (10–50 g), and the exotherm associated with the periodinane quench (temperature rise of 15 °C in 30 s at 50 g scale) necessitates jacketed reactors with rapid cooling capability for any scale-up. Incompatibility with amine-based additives is documented: even trace tertiary amines accelerate decomposition of the periodinane to acetate by-products that co-elute with the aldehyde, reducing isolated purity.
A parallel synthetic path exploits the alcohol as a directing group in iridium-catalysed C–H borylation. Using [Ir(OMe)(cod)]2 (0.5 mol%) and 4,4′-di-tert-butyl-2,2′-bipyridine (1 mol%) in hexane, the C5 position of the thiazole ring is borylated with bis(pinacolato)diboron (B2pin2, 1.05 eq.) at 60 °C in 24 h. The hydroxymethyl group remains intact, giving a tri-functionalised intermediate (alcohol, boronate ester, thiazole nitrogen) ready for sequential orthogonal coupling. No separate protection step is required, a contrast to the behaviour of 2-aminothiazole where the amine competes for the catalyst and must be masked as the acetamide, lowering overall yield by 15–25%.
2-(Hydroxymethyl)-1,3-thiazole 97% is shipped in compliance with IATA Dangerous Goods Regulations for corrosive liquids (Class 8, UN 3265) when transported in glass ampoules. Bulk containers use fluorinated HDPE drums with a maximum fill volume of 80% to accommodate thermal expansion. The product has been pre-registered under EU REACH for tonnage band 1–10 t/a; full registration data is accessible via the SIEF platform. On receipt, immediate nitrogen blanketing and storage at the recommended temperature mitigate the formation of peroxides and colour bodies, maintaining the utility of this intermediate in reaction sequences demanding tight impurity budgets.
