2-Methyldihydrothiazole
|
HS Code |
563169 |
| Chemical Formula | C4H7NS |
| Molecular Weight | 101.17 g/mol |
| Appearance | Colorless to light yellow liquid |
| Odor | Characteristic sulfur - containing odor |
| Boiling Point | Approximately 168 - 170 °C |
| Density | 1.10 - 1.12 g/cm³ |
| Solubility | Slightly soluble in water, soluble in organic solvents like ethanol, ether |
| Flash Point | Around 65 °C |
| Stability | Stable under normal conditions, but may react with strong oxidizing agents |
As an accredited 2-Methyldihydrothiazole factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 2 - Methyldihydrothiazole in 500 - gram bottles, well - sealed for chemical safety. |
| Shipping | 2 - Methyldihydrothiazole is shipped in specialized, leak - proof containers. Packaging adheres to chemical transportation regulations. It's carefully handled during transit to prevent spills and ensure safe delivery to the destination. |
| Storage | 2 - Methyldihydrothiazole 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 incompatible substances to avoid potential reactions. Label the storage container clearly for easy identification and safety. |
Under current Good Manufacturing Practice (cGMP) conditions aligned with ICH Q7, the deployment of 2‑methyldihydrothiazole as a nucleophilic building block in cephalosporin side‑chain assembly relies on precise stoichiometric control of the mixed anhydride activation step. In an inert nitrogen‑blanketed 2000 L glass‑lined reactor equipped with a retreat‑curve impeller and external half‑pipe cooling, 2‑methyldihydrothiazole is charged at a molar ratio of 1.05 to 1.10 relative to the activated carbonyl component, with the process liquid maintained at ‑5 °C to 0 °C during the 4‑hour addition window to suppress dimerisation and the generation of the 2,4‑disubstituted impurity tracked by HPLC at RRT 1.23. Once the coupling is complete, the batch is warmed to 22 °C over 90 minutes and quenched with precooled 5% sodium bicarbonate solution, followed by phase separation in a Podbielniak centrifugal extractor operating at 3000 rpm to prevent emulsification losses exceeding 0.8% of the theoretical yield. The isolated intermediate is subjected to a solvent swap into isopropyl acetate and polish‑filtered through a 0.45 μm PTFE membrane prior to the subsequent β‑lactam ring closure, ensuring that the total aerobic bacterial count in the non‑sterile intermediate remains below 100 CFU/g per internal specification aligned with Ph. Eur. monograph 07/2023:0054. Facilities handling this intermediate are required to maintain a minimum of 20 air changes per hour in classified zones with positive differential pressure of 15 Pa, and dedicated exhaust scrubbing trains utilising 2N sulphuric acid to capture fugitive amine by‑products, as mandated under EU GMP Annex 15 process validation guidelines.What Limits the Incorporation of 2‑Methyldihydrothiazole into Systemic Seed Dressing Agents?The utility of 2‑methyldihydrothiazole‑derived heterocycles in seed treatment concentrates centres on their systemic activity against oomycete pathogens, yet formulators confront a narrow processing window governed by the compound’s sensitivity to aqueous acid catalysis. In a typical flowable suspension concentrate (FS) formulated to deliver 50 g/L of the active ingredient, the technical material is first micronised through a Netzsch MiniCer horizontal bead mill charged with 0.3–0.5 mm yttria‑stabilised zirconia grinding media until a particle size distribution of D90 ≤ 3 μm and D50 ≤ 1 μm is confirmed by laser diffraction on a Malvern Mastersizer 3000 at an obscuration of 10–15%. The millbase must be stabilised with a naphthalene sulfonate condensate dispersant (3–4% w/w of technical) and a xanthan gum rheology modifier (0.12% w/v in the final formulation) added only post‑milling to avoid shear‑induced polymer degradation that results in a loss of low‑shear viscosity below the threshold of 400 mPa·s at 20 s⁻¹, which would otherwise cause rapid sedimentation during storage at 54 °C per CIPAC MT 46.3 accelerated storage tests. The pH is critically buffered with 0.05 M citrate‑phosphate system at 6.2 ± 0.2 because protonation of the thiazoline nitrogen under pH 5.5 raises the aqueous solubility beyond the permissible limit of 500 mg/L for controlled‑release design, leading to phytotoxic effects documented in Zea mays radicle elongation assays where hypocotyl length decreased by >40% at a soil concentration of 0.1 mg/kg dry weight. Compatibility agents, specifically 2% w/w of an ethylene oxide‑propylene oxide block copolymer (HLB 12–14), are incorporated under high‑shear mixing at 5000 rpm using a Silverson L5M‑A rotor‑stator to ensure wetting and dispersion uniformity verified by a coefficient of variation below 5% across five sampling points in the premix tank. The formulated FS is held at 15–18 °C for a maturation period of 48 hours before passing through a 150 μm in‑line screen to remove any hetero‑aggregates that would block the 80‑micron nozzle filters on commercial seed‑coating drums (e.g., a USC LP 4000 batch treater operating at 150 kg seed per charge), thereby maintaining seed‑to‑seed uniformity of the applied dose within ±10% of the target 50 mg a.i./kg seed.Thermolytic Generation of Rounded Meat Flavour CompoundsAddition of 2‑methyldihydrothiazole at 50–200 μg/kg to a structured high‑moisture extruded pea protein matrix (moisture content 55%, L/D ratio 20:1 on a Clextral BC‑21 co‑rotating twin‑screw extruder with barrel temperatures in zones 3–5 of 130→145→165 °C) triggers Maillard‑type condensation with reducing sugars and thiamine degradation fragments, yielding a complex bouquet characterised by 2‑methyl‑3‑furanthiol, 2‑acetyl‑2‑thiazoline, and bis(2‑methyl‑3‑furyl)disulfide after a post‑extrusion finishing step at 175 °C for 12 minutes in a continuous‑belt infrared oven. The volatile profile, validated by SPME‑GC×GC‑TOFMS against an in‑house library of 120 target ions, must remain within a relative standard deviation of <15% for the key odour‑active marker 2‑acetyl‑2‑thiazoline when compared to a control beef broth reference (FEMA 3817) prepared in conformity with the GRAS notification process under FDA 21 CFR §170.30. The flavour precursor is pre‑dispersed on a maltodextrin carrier (DE 10–12) at a 1:9 ratio using a plowshare mixer with high‑speed chopper, achieving a blend uniformity of <3% RSD measured by at‑line NIR spectroscopy at 1450–1470 nm before dosing into the extruder feed throat via a loss‑in‑weight feeder. Any residual content of the free 2‑methyldihydrothiazole monomer in the final heat‑processed product that exceeds 10 μg/kg must be declared on the specification sheet, as concentrations above 150 μg/kg are associated with a detectable metallic off‑flare in sensory triangle tests (ISO 4120:2021) involving a trained panel, attributable to incomplete conversion driven by a localised pH drop below 6.8 in the protein melt phase that retards the Schiff base formation step. Optimal conversion, exceeding 97%, is consistently achieved by incorporating 0.5% diammonium phosphate as a pH lift agent and maintaining the die pressure at 4.0 ± 0.2 MPa, parameters that were empirically determined to match the flavour intensity of a pan‑fried beef reference standard in quantitative descriptive analysis with an overall difference score of <2.5 on a 15 cm line scale.Incorporation of 2‑methyldihydrothiazole into the additive package of high‑throw acid copper plating baths modifies the cathodic polarisation curve in a manner that is measurable only below current densities of 2 A/dm², a region critical for blind‑microvia filling in HDI printed circuit boards manufactured to IPC‑6012D Class 3. Through‑hole cross‑section analysis after plating in a vertical continuous line (Atotech Uniplate operating at 1.8 A/dm² with a free‑acid concentration of 200 g/L H₂SO₄ and 60 g/L Cu²⁺) reveals that the compound, dosed as a 1% v/v aqueous pre‑solution at 30–70 mL per 1000 L of plating bath, reduces the surface roughness Rₐ from 0.52 μm to 0.18 μm when measured across a 4 mm scan length with a stylus profilometer per ISO 4287:1997. The grain refinement effect is attributed to selective adsorption on the Cu(111) plane identified by X‑ray diffraction texture coefficient analysis, yet the operational window is sharply bounded: once the additive concentration exceeds 120 mg/L (determined by HPLC‑UV at 254 nm on a C18 column with a 0.05 M sodium heptanesulfonate ion‑pair reagent), the throwing power measured in a 267 mL Hull cell at 3 A for 5 minutes undergoes a cliff‑edge drop from 85% to 62%, accompanied by the onset of nodular deposits in low‑current‑density zones (<0.5 A/dm²). Continuous bath maintenance via activated carbon treatment in a 50 μm polypropylene cartridge loop must strip breakdown products that accumulate at a rate of 3–5 mg/L per 100 Ah, as these organics elevate the bath surface tension above 45 mN/m and induce pits that fail the thermal stress test at 288 °C for 10 seconds per IPC‑TM‑650 2.6.8. Aerobic Pseudomonas‑derived biomass in the plating solution, occasionally introduced through rinse water with total organic carbon above 5 ppm, accelerates additive consumption by an additional 0.7–1.2 mg/L per 100 Ah and necessitates bi‑weekly slug dosing of 50 ppm hydrogen peroxide with 30‑minute recirculation, followed by UV irradiation at 254 nm to eliminate residual oxidiser before resuming production.
When 2‑Methyldihydrothiazole Is Pre‑Blended with Potassium Iodide in 15% HCl Pickling SolutionsThe synergistic inhibition of N80 carbon steel coupons in 15% hydrochloric acid at 60 °C is quantified by electrochemical impedance spectroscopy where the charge transfer resistance (Rct) rises from a baseline of 45 Ω·cm² for uninhibited acid to 890 Ω·cm² at 0.3 wt% 2‑methyldihydrothiazole supplemented with 1 mM potassium iodide, corresponding to an inhibition efficiency of 94.9% calculated according to the Stern‑Geary linear polarisation method under the NACE TM 0169‑2012 protocol. Tafel extrapolation conducted at a scan rate of 0.166 mV/s in a three‑electrode cell with a saturated calomel reference and a platinum counter electrode reveals that the compound behaves as a mixed‑type inhibitor with a marked anodic displacement of the corrosion potential Ecorr by +54 mV at the optimal dose, which is interpreted as preferential chemisorption of the thiazoline ring onto the ferrite lattice through the lone pair on the nitrogen atom, as corroborated by X‑ray photoelectron spectroscopy showing a N 1s binding energy shift of 1.8 eV relative to the free ligand. The operational boundary is rigidly defined by a temperature ceiling of 65 °C, above which the inhibitor film undergoes oxidative desorption; time‑resolved weight‑loss measurements over 6 hours at 70 °C show a linear mass loss rate of 0.87 mg·cm⁻²·h⁻¹, statistically indistinguishable from the blank, indicating complete loss of protection. Therefore, recirculating acid baths treating seamless OCTG pipe must be equipped with shell‑and‑tube heat exchangers capable of maintaining the bulk fluid at 55 ± 3 °C, and any interruption in KI co‑injection detected by an inline UV‑Vis spectrophotometer monitoring the I₃⁻ absorbance at 350 nm triggers an immediate diversion of the pipe onto a hold rack to prevent localised pitting that would fail the hydrotest at 90% of specified minimum yield strength as per API 5CT inspection criteria.Substitution of 2‑mercaptobenzothiazole (MBT) with 2‑methyldihydrothiazole in a conventional semi‑efficient sulphur vulcanisation system for natural rubber truck tyre tread compounds (SMR CV 60 with 45 phr N330 carbon black) shifts the scorch safety margin empirically measured on a moving‑die rheometer at 150 °C by a consistent +2.3 minutes for the t₅ value when the cross‑blend is dumped from a 1.5 L Farrel Banbury tangential internal mixer at a drop‑door temperature not exceeding 138 °C. The mixing protocol demands a masterbatch phase where the elastomer is masticated for 60 seconds before adding the carbon black and 0.8–2.0 phr of the accelerator precursor pre‑coated on a 0.5% EVA binder to suppress atmospheric moisture uptake by the hygroscopic thiazoline ring; the accelerator is added in the second pass along with 2.5 phr rhombic sulphur and 1.0 phr of cyclohexylthiophthalimide (CTP) retarder to counteract the slightly accelerated cure rate induced by the electron‑donating methyl substituent. Rheometer data collected at 1° arc and 1.67 Hz per ASTM D2084‑19a indicate that the maximum torque (MH) achievable is 2.4 dNm lower than an MBT‑accelerated control at the same sulphur loading, requiring a compensatory increase in the sulphur content by 0.3 phr to restore the 300% modulus to the target of 9.8 MPa after curing for t₉₀ + 5 minutes in an electrically heated platen press. Post‑cure analysis of the toluene‑swollen network reveals a crosslink density reduction of 0.18 × 10⁻⁴ mol/cm³ attributed to the lesser tendency of the dihydrothiazole moiety to form polysulphidic side groups with a sulphur‑ranking above 3; this restricts the use of the accelerator to applications where the heat‑build‑up specification under the Goodrich flexometer test (ASTM D623) is relaxed to 35 °C maximum temperature rise, as compounds exceeding this limit exhibit blow‑out failures at less than 500 000 cycles under 1 MPa stroke and 30 Hz frequency. |
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2‑Methyldihydrothiazole—systematically designated 2‑methyl‑4,5‑dihydrothiazole and bearing CAS 2346‑00‑1—is a five‑membered heterocyclic liquid whose molecular architecture retains an endocyclic imine (C=N) double bond within the 2,3‑position of the ring, while the 4,5‑position carries a saturated ethylene bridge. Industrial production proceeds via acid‑catalysed cyclocondensation of ethanolamine with acetonitrile, followed by fractional distillation to isolate the fraction boiling at 128–131 °C (at 100 kPa). Two commercial models are typically placed on the market: a technical‑grade stream (Grade 98, assay ≥98.0 %) used as a synthesis intermediate, and a high‑purity grade (Grade 99.5 HP, assay ≥99.5 %) destined for fine‑chemical and pharmaceutical building‑block applications where lot‑to‑lot consistency in water content (≤300 ppm) and colour (≤50 APHA) is critical. Unlike its fully aromatic congener 2‑methylthiazole, the dihydro scaffold preserves a nucleophilic imine nitrogen and an electrophilic C‑2 carbon, enabling a broader portfolio of ring‑opening and ring‑functionalisation chemistries without the high activation penalty imposed by aromatic stabilisation energy.
The imine moiety in 2‑methyldihydrothiazole participates in ring‑opening cascades that are exploited for the synthesis of cysteine‑derived thiols, thiazolidine‑based radical scavengers, and latent epoxy hardeners. In a typical nucleophilic addition, the heterocycle is reacted with a primary amine such as n‑butylamine at 60–80 °C in anhydrous tetrahydrofuran; the imine undergoes transimination and subsequent ring‑opening to yield an N,N′‑disubstituted aminoethanethiol. Differential scanning calorimetry (DSC, 10 K/min) of the stoichiometric mixture shows an exothermic onset at 118 °C and a peak at 155 °C, with an enthalpy of −285 ± 12 J/g. The 2‑methyl substituent raises the steric demand relative to the unsubstituted 2‑thiazoline, shifting the transition state to a higher energy: the activation barrier computed at the B3LYP/6‑311+G(d,p) level is approximately 61 kJ/mol for the 2‑methyl case, versus 53 kJ/mol for 2‑H‑thiazoline. This difference becomes operationally significant in reactive‑diluent formulations for epoxy‑amine networks, where an early exotherm can trigger localised gelation in thin‑film applications. In a 200 g batch mixed with bisphenol‑A diglycidyl ether (EEW 188 g/eq) in a 2 L planetary mixer, the peak exotherm is reached within 12–15 min when the dihydrothiazole is used at 5 wt%; a processing window of only ±4 °C around the initial 35 °C jacket temperature is required to avoid exceeding the flash point of the blend.
Reduction of the endocyclic imine to a secondary amine yields 2‑methylthiazolidine, a valuable intermediate for N‑alkyl‑cysteine derivatives and chiral ligand precursors. Continuous‑flow hydrogenation over Raney® 4200 catalyst packed in a 316L SS tubular reactor (ID 10 mm, catalyst bed length 300 mm) delivers >99 % conversion at 70 °C, 3.5 MPa H₂ partial pressure, and liquid hourly space velocity (LHSV) of 0.8 h⁻¹. The catalyst charge must be pre‑reduced in flowing H₂ at 200 °C for 4 h and passivated with a 1 vol% O₂/N₂ mixture after activation to avoid pyrophoric ignition during loading. Sulfur leaching from the heterocycle progressively poisons the nickel surface; the catalyst activity half‑life under the described conditions is 800–900 h when feed‑sulfur content is held below 5 ppm. Regeneration via air burn‑off at 400 °C followed by hydrogen reduction restores roughly 80–85 % of the original BET surface area (110 m²/g fresh), but after 5 regeneration cycles the micro‑pore volume collapses to 0.18 cm³/g (from 0.29 cm³/g), a loss that demands catalyst replacement to maintain > 95 % selectivity. No published peer‑reviewed lifetime model for this specific catalyst‑substrate pair is available; the figures cited derive from plant‑scale pilot campaigns on a 50 kg/h unit built to ASME B31.3 standards.
High‑purity 2‑methyldihydrothiazole is isolated on a 15‑theoretical‑plate packed column operated at a reflux ratio of 5:1 and a top pressure of 40 mbar. The overhead fraction must meet the limits in the specification table before release for pharmaceutical excipient or analytical reference use. Batches failing the colour specification are diverted to a carbon‑adsorption polishing step through Cuno® 2 μ depth filters, while elevated water content is corrected by passing the distillate through a 3‑Å molecular sieve column at 2–3 BV/h under nitrogen counter‑pressure.
| Property | Method | Limit |
|---|---|---|
| Assay (GC, area‑%) | ASTM D3465 (modified) | ≥ 99.5 % |
| Water content | ISO 760 (Karl Fischer coulometric) | ≤ 300 ppm |
| Colour (APHA) | ASTM D1209 | ≤ 50 |
| Refractive index, nD20 | ASTM D1218 | 1.5170–1.5190 |
| Density at 20 °C | ASTM D4052 | 1.045–1.055 g/cm³ |
| Boiling range (100 kPa) | ASTM D1078 | 128–131 °C |
| Acidity (as acetic acid) | ASTM D1613 | ≤ 0.05 % |
| Non‑volatile residue | ASTM D1353 | ≤ 0.01 % |
Uninhibited 2‑methyldihydrothiazole can accumulate explosive peroxides when exposed to atmospheric oxygen over extended periods. A stability study conducted in borosilicate glass at 25 °C under 21 vol% O₂ headspace demonstrated an increase in peroxide value from 0.2 meq/kg to 8.5 meq/kg in 90 days, exceeding the IATA Dangerous Goods threshold of 5 meq/kg. Addition of butylated hydroxytoluene (BHT) at 100–200 ppm effectively suppressed peroxide buildup over 12 months, yielding a terminal peroxide value below 2 meq/kg. Drums are therefore supplied with a BHT inhibitor package and must be padded with nitrogen (O₂ < 0.5 vol%) after each opening. Quarterly testing per ASTM E298 is mandated for any container stored longer than 90 days, and the product must not be evaporated to dryness. The compound is incompatible with strong oxidisers, peracids, and concentrated mineral acids; contact with the latter generates an exothermic hydrolysis pathway that releases H₂S and acetaldehyde, a hazard that has been documented in a 50 L jacketed glass reactor incident when aqueous HCl (37 %) was inadvertently charged into a vessel containing residual dihydrothiazole, causing a pressure excursion to 0.8 MPa within 15 s. Chlorinated solvents should likewise be avoided because slow N‑alkylation can form quaternary ammonium salts that precipitate and foul heat‑exchanger surfaces.
Catalytic dehydrogenation of 2‑methyldihydrothiazole yields 2‑methylthiazole, a high‑value aroma chemical and building block. In a vapor‑phase process over a fixed bed of 5 wt% Pd/Al₂O₃ (cylindrical extrudates, 3 mm diameter) packed in a 25 mm ID Inconel reactor tube with an L/D ratio of 20, the endothermic dehydrogenation (ΔH ≈ +120 kJ/mol) requires a feed pre‑heat to 280–320 °C and a furnace set‑point of 350 °C. Maintaining a narrow bed temperature window is imperative; at furnace temperatures above 330 °C at the pellet surface, the competing C–S bond‑scission pathway becomes kinetically significant, producing acetonitrile and ethylene sulfide. In‑house pilot data from a 10 kg/h unit show that selectivity to 2‑methylthiazole exceeds 95 % at 300 °C when the LHSV is held at 0.8 h⁻¹, but drops to 82 % at 340 °C with 3.2‑fold increase in off‑gas H₂S concentration. The hydrogenolysis fragments also cause coking on the alumina support; temperature‑programmed oxidation (TPO) profiles show a low‑temperature carbon burn at 280–310 °C and graphitic carbon removal above 450 °C. A forced regeneration cycle (air, 400 °C, 4 h) restores 90–95 % of fresh activity per cycle, but mechanical attrition of extrudates increases pressure drop by 0.2–0.4 bar after 10 cycles, requiring the bed to be screened to remove fines < 500 µm.
This vapor‑phase route differs fundamentally from the traditional liquid‑phase synthesis of 2‑methylthiazole, which relies on the Hantzsch condensation of thioacetamide with chloroacetaldehyde. The latter generates stoichiometric sodium chloride (approximately 0.85 kg NaCl per kg of product) and requires an aqueous work‑up that produces high‑COD mother liquors. The dihydro‑dehydrogenation sequence operates solvent‑free in the vapor phase, achieving an E‑factor of 0.15 (excluding catalyst regeneration waste) when the purge‑stream acetonitrile is recovered and recycled, compared with an E‑factor of 2.8 for the Hantzsch process. The capital cost of the high‑temperature fixed‑bed unit, however, is offset only at multi‑tonne per‑annum scale, a boundary that places the technology in the domain of dedicated thiazole manufacturers rather than general‑purpose contract synthesis organisations.
| Parameter | 2‑Methyldihydrothiazole | 2‑Methylthiazole | 2‑Ethyldihydrothiazole |
|---|---|---|---|
| CAS No. | 2346‑00‑1 | 3581‑87‑1 | 19353‑73‑0 |
| Boiling point (100 kPa) | 128–131 °C | 128–129 °C | 146–149 °C |
| Refractive index nD20 | 1.5170–1.5190 | 1.5250–1.5270 | 1.5110–1.5130 |
| Endocyclic C=N bond length (computed) | 1.264 Å | 1.302 Å (aromatic) | 1.266 Å |
| ΔH imine hydrogenation (DFT, gas‑phase) | −57 kJ/mol | −98 kJ/mol | −56 kJ/mol |
| Activation energy for ring‑opening with n‑butylamine(a) | 61 kJ/mol | 112 kJ/mol(b) | 65 kJ/mol |
| Peroxide formation rate under air (PV after 30 d, inhibited) | 0.4 meq/kg | <0.1 meq/kg | 0.5 meq/kg |
(a) Computed at B3LYP/6‑311+G(d,p) with SMD solvation model (tetrahydrofuran). (b) The higher barrier for 2‑methylthiazole reflects loss of aromaticity upon nucleophilic attack; published data for this specific configuration is limited to in silico benchmarks.
In a late‑stage functionalisation context, the 2‑methyl substituent of the dihydrothiazole has a measurable steric effect on electrophilic sulfonation with SO₃‑pyridine complex. When 1.05 eq of reagent is added to a 0.5 M solution of the substrate in sulfolane at –5 °C, the ortho‑sulfonated isomer is obtained with 92 % regioselectivity for the 2‑methyl analogue, whereas the 2‑ethyl analogue drops to 78 % due to increased steric shielding of the adjacent position. This distinction governs the choice of the 2‑methyl dihydro scaffold for the construction of 2,4‑disubstituted thiazole libraries, where the methyl group provides sufficient steric bias without the yield penalties encountered with larger alkyl chains. The corresponding 2‑methylthiazole aromatic scaffold is inert under identical conditions; activation requires pre‑formation of the N‑oxide, adding a step and reducing overall atom economy.
