S-(4-Chlorophenyl) chlorothiolformate - ≥95% , CAS No.13606-10-5

CAS: 13606-10-5 Cat. No.: S984268 Fórmula: C₇H₄Cl₂OS Peso molecular: 207.080 Número CE: 667-645-3

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Especificações e pureza

≥95%

Condições de armazenamento de armazenamento

Room temperature

Pureza

≥95%

Nomes e identificadores

Sorrisos canónicos

C1=CC(=CC=C1SC(=O)Cl)Cl

IUPAC Name

S-(4-chlorophenyl) chloromethanethioate

InChIKey

LCPSYCACCNXGDA-UHFFFAOYSA-N

INCHI

1S/C7H4Cl2OS/c8-5-1-3-6(4-2-5)11-7(9)10/h1-4H

Peso molecular

207.080

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organosulfur compounds
    • Classe Thioethers
      • Subclass Aryl thioethers

• Kingdom: Organic compounds
• Superclass: Organosulfur compounds
• Classe: Thioethers
• Subclass: Aryl thioethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Aryl thioethers
• Alternative Parents: Chlorobenzenes Aryl chlorides Organic carbonic acids and derivatives Sulfenyl compounds Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Aryl thioether - Chlorobenzene - Halobenzene - Aryl chloride - Aryl halide - Monocyclic benzene moiety - Benzenoid - Carbonic acid derivative - Sulfenyl compound - Organic oxygen compound - Organohalogen compound - Organochloride - Organooxygen compound - Carbonyl group - Hydrocarbon derivative - Organic oxide - Aromatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as aryl thioethers. These are organosulfur compounds containing a thioether group that is substituted by an aryl group.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Propriedades químicas e físicas

• Peso molecular: 207.080 g/mol
• XLogP3: 3.900
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 205.936 Da
• Monoisotopic Mass: 205.936 Da
• Topological Polar Surface Area: 42.400 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 143.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No biological assay or immunoassay protocols apply to this small‑molecule reagent. For synthetic applications, see Reaction Conditions and Application notes. Any procedures should be conducted in dry, aprotic organic media under inert atmosphere with appropriate base and temperature control.

Biological Roles

This product is a small, synthetic S‑aryl acyl chloride reagent and does not have an inherent biological role. Any interactions with biomolecules arise from its general electrophilicity rather than selective binding or signaling.

• General considerations (literature)

  • Highly reactive toward nucleophilic residues (e.g., lysine, serine, cysteine) and water; therefore, it is unsuitable for direct biological systems except as a chemical modifier in vitro under controlled conditions.
  • Hydrolysis produces HCl and thiophenolic species (e.g., 4‑chlorothiophenol derivatives), which can be cytotoxic/irritant.

• Research context

  • Occasionally used to derivatize alcohols or amines on small molecules/bioconjugates to form thiocarbonates or carbamothioates prior to further transformations. Such usage is entirely chemical and performed in organic media; it is not a buffer component or biologically compatible reagent.

No biological function, pathway involvement, or receptor specificity is attributed to S‑(4‑chlorophenyl) chlorothiolformate itself. For biological studies, any exposure should be minimized and confined to contained chemical synthesis workflows.

Buffer Applications

Not typically applicable. S‑(4‑chlorophenyl) chlorothiolformate is moisture‑reactive and incompatible with aqueous buffers, alcohol‑containing media, and amine‑containing buffers. It hydrolyzes to release HCl and thiophenolic species.

For laboratory use, keep this reagent strictly in dry, aprotic organic solvents. See Solvent Selection, Reaction & Applications, and Reaction Conditions for relevant, non‑aqueous protocols.

Green Alternatives

Chlorothioformates offer convenient reactivity but entail hazards typical of acyl chlorides (HCl release, hydrolysis) and reliance on chlorinated solvents. Greener strategies can reduce risk and environmental footprint while maintaining performance.

• Reagent alternatives (literature)

  • Thiocarbonyl diimidazole (TCDI): solid, phosgene‑free reagent for thiocarbonate/thiocarbamate formation; byproduct is imidazole (benign, easily removed).
  • 1,1′‑Carbonyldiimidazole (CDI) plus thiols: routes to thiocarbonates/carbamothioates without HCl evolution (sequence dependent).
  • Triphosgene or carbonyl di(1,2,4‑triazole) as phosgene surrogates when carbonate chemistry is central; evaluate sulfur incorporation steps.

• Solvent swaps (typical)

  • Replace DCM/CHCl3 with EtOAc or 2‑MeTHF where solubility permits; both offer improved EHS profiles and better biorenewable content (2‑MeTHF).
  • Use toluene instead of chlorinated solvents for higher‑temperature steps; ensure dry conditions.

• Comparison snapshot (general)

  • Chlorothioformate (this item): high electrophilicity; generates HCl; moisture sensitive; typically fast at 0–25 C.
  • TCDI: milder, less corrosive; may require longer times/higher temps; forms imidazolide intermediates.
  • 2‑MeTHF vs DCM: greener, higher bp aids heat management; may alter rates/selectivity—optimize base and temperature.

Implement in‑process controls to minimize waste: titrate water content, employ inline drying, meter additions, and quench HCl with carbonate scrubbers.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item. It is a research‑grade synthetic reagent.

• Process chemistry context (literature, non‑specification)

  • Used as a carbonylation/acylation synthon to prepare thiocarbonates and carbamothioates en route to APIs or intermediates under strictly anhydrous, non‑GMP development settings.
  • HCl evolution and potential for thiophenol formation necessitate robust containment and scrubbing on scale; solvent selection (EtOAc/toluene/2‑MeTHF) can improve EHS profiles compared to DCM.

• Formulation roles

  • None. This reagent is not used as a formulation excipient or processing aid in finished dosage forms.

All uses are for research and laboratory synthesis only. For any cGMP deployment, full impurity, residual reagent, and quench product clearance studies are required and must be developed independently.

Physical Properties

Item-specific physical property specifications are not provided in the Product Data.

• Item-specific values

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general reference values (non-specification)

  • Approximate formula: C7H4Cl2OS; formula mass ~207.07 g/mol (calculated from atomic weights).
  • Physical state: typically a colorless to pale yellow liquid for many S‑aryl chlorothioformates; may darken on storage by trace hydrolysis/oxidation.
  • Boiling point: often decomposes before or during distillation; many chlorothioformates have bp in the 220–260 C range at ambient pressure; lower under reduced pressure (literature, compound‑class guidance).
  • Density: frequently in the 1.3–1.5 g/mL range for chlorinated, sulfur‑containing aryl acyl chlorides (literature, class trend).
  • Solubility: miscible with common aprotic organic solvents (DCM, chloroform, toluene, THF, EtOAc); reacts with water/alcohols (literature).
  • Refractive index: typically nD ~1.56–1.60 for related S‑aryl chlorothioformates (literature, class trend).

Note: Use literature values only as planning aids. For critical work, obtain the exact lot-specific data from the CoA/Spec Sheet.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for this reagent class (literature/industry practice):

• For sensitive synthesis (e.g., formation of thiocarbonates/carbamothioates used in subsequent stereospecific steps), low hydrolyzable chloride and low acid content are desirable. If grade is unspecified, verify by titration or test reaction on small scale.
• UV/Vis or HPLC grades are not commonly assigned to chlorothioformates. If using in analytical contexts, pre‑purify by bulb‑to‑bulb distillation under high vacuum or pass through a short plug of basic alumina under inert atmosphere to remove acidic impurities (general practice; validate for your use).
• Water content/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet. Given moisture sensitivity, Karl Fischer moisture verification is recommended prior to moisture‑critical transformations.
• If multiple grades are available, select based on downstream needs:
  • Synthesis grade: acceptable for routine acylations where traces of HCl are tolerable.
  • High‑purity grade: preferred for base‑sensitive nucleophiles or when minimizing byproduct formation is critical.

Reaction and Applications

S‑aryl chlorothioformates such as S‑(4‑chlorophenyl) chlorothiolformate are versatile electrophiles for introducing the thiocarbonyl carbonyl unit under mild conditions.

Key application families (literature, non‑specification):

• Formation of O‑aryl thiocarbonates from alcohols
  • ROH + ArSCOCl → ArSCOOR (base, often DMAP). These thiocarbonates serve as protecting groups or as intermediates toward eliminations and rearrangements. With vicinal diols, cyclic thiocarbonates can be prepared.
• Synthesis of carbamothioates (thiocarbamates) from amines
  • RNH2 + ArSCOCl → ArSCO(NHR). Useful for modulating basicity/lipophilicity of amines and as masked isothiocyanate equivalents in some sequences.
• Installation of thiocarbonyl activation for downstream transformations
  • Thiocarbonates can undergo reductions, radical deoxygenations, or be leveraged in eliminative processes (e.g., transforming 1,2‑diols via cyclic thiocarbonates in Corey–Winter–type sequences; reagent systems vary by protocol).
• Mixed anhydride strategies
  • Transient activation enables coupling to form thioesters or carbonate congeners in multistep schemes (verify chemoselectivity against competing nucleophiles).

Practical tips

• Use 1.0–1.2 equiv of ArSCOCl with 1.5–2.0 equiv of an HCl scavenger (Et3N, DIPEA, or pyridine). DMAP (5–10 mol%) accelerates alcohol acylation markedly.
• Add the chlorothioformate dropwise to the nucleophile/base mixture at 0–5 C to control exotherm; then warm to 20–25 C to complete conversion.
• Monitor by TLC/LC–MS; watch for hydrolysis products (4‑chlorothiophenol derivatives) if moisture ingress occurs.

Reaction Conditions

Generalized, literature‑based conditions for this reagent class (optimize per substrate):

• Thiocarbonate formation (alcohols)

  • Solvent: dry DCM or toluene; THF also suitable.
  • Base: Et3N or pyridine (1.5–2.0 equiv); DMAP 5–10 mol% as acylation catalyst.
  • Temperature: 0–5 C for addition, then 20–25 C for 1–3 h. Sterically hindered alcohols may require gentle reflux in toluene.
  • Typical outcome: clean conversion to ArSCOOR; isolated yields frequently 70–95% (literature range).

• Carbamothioate formation (amines)

  • Solvent: dry DCM, THF, or EtOAc.
  • Base: DIPEA, Et3N, or pyridine (≥2.0 equiv) to neutralize HCl.
  • Temperature: maintain 0–5 C during addition to suppress over‑acylation/side reactions; warm to rt for completion (1–4 h).

• Workup and purification

  • Quench residual acyl chloride at 0 C with saturated aqueous NaHCO3 or dilute Na2CO3 (cautiously; gas evolution); separate organic layer quickly to limit hydrolysis.
  • Wash with brine, dry (Na2SO4), concentrate under reduced pressure at ≤30 C. Purify by column chromatography using hydrocarbon/EtOAc mixtures; avoid silica pre‑exposed to water.

• Practical notes

  • Strictly exclude moisture (oven‑dried glassware, inert atmosphere). Metered addition via syringe pump aids heat control.
  • Monitor for thiophenolic byproducts by LC–MS; add base incrementally if HCl accumulation is evident.

Safety and Handling

• Product Data hazard fields are not populated for this item. Always consult the SDS for authoritative classification.

  • Signal word: Not specified for this item; refer to SDS.
  • GHS classification/pictograms: Not specified for this item; refer to SDS.

• General hazards of S‑aryl chlorothioformates (literature, non‑specification)

  • Corrosive acyl chloride functionality: causes severe skin and eye burns; strong respiratory irritant; potential lachrymator.
  • Moisture‑reactive: hydrolyzes to release HCl and carbonyl derivatives; may liberate 4‑chlorothiophenol and CO2 upon further decomposition; pungent odor possible.
  • Sensitization/odor: thiols formed on hydrolysis are malodorous; control vapors with efficient ventilation.

• Handling and PPE (best practice)

  • Work strictly anhydrous when possible; use dry glassware and inert atmosphere for weighing/transfers.
  • Use in a certified chemical fume hood. Wear splash goggles or face shield, gloves (laminate/fluoroelastomer preferred over simple nitrile for acyl chlorides), lab coat.
  • Avoid contact with bases, amines, alcohols, and water unless intended; violent exotherms possible.

• First aid (overview; defer to SDS)

  • Skin/eye: immediate copious water rinse for ≥15 minutes; remove contaminated clothing; seek medical attention.
  • Inhalation: move to fresh air; medical evaluation if symptoms persist.
  • Ingestion: do not induce vomiting; rinse mouth; urgent medical care.

• Storage incompatibilities

  • Keep away from water, alcohols, amines, strong bases, oxidants, and reducing agents. Use moisture‑impermeable caps and desiccation.

Solvent Selection

This compound is an acyl chloride that is moisture‑sensitive and reactive with protic media. Solvent choice should prioritize aprotic, dry environments and effective heat removal.

• Polarity/miscibility (literature)

  • Readily soluble in chlorinated solvents (DCM, CHCl3), aromatic hydrocarbons (toluene), and ethers (THF, MTBE) when dry.
  • Insoluble/unstable in water; reacts with alcohols and amines.

• Typical solvent choices by application

  • Nucleophilic acylation of alcohols to thiocarbonates: dry DCM or toluene; catalytic DMAP often used. DCM affords easy temperature control (0–25 C) and rapid stirring; toluene enables higher‑temperature driving force if needed.
  • Carbamothioate formation with amines: DCM, THF, or EtOAc under cooling (0–5 C) to moderate exotherm; add base (Et3N, DIPEA, or pyridine) as HCl scavenger.
  • Scale‑up: toluene or EtOAc favored for greener profiles and heat capacity; ensure dryness (molecular sieves, in‑line drying columns).

• Comparison (general considerations)

  • DCM: excellent control and solvency; regulatory/green concerns.
  • Toluene: good solvency; higher bp allows staged additions; lower dielectric than DCM.
  • THF/2‑MeTHF: good for heterogeneous bases; may require lower temperatures to suppress side reactions; ensure inhibitor‑free, dry solvent.

Always dry solvents (molecular sieves or distillation) and verify by Karl Fischer where water sensitivity is critical.

Storage and Reconstitution

• Storage conditions (from Product Data)

  • Store at room temperature.

• Additional best practices (general for chlorothioformates; non‑specification)

  • Keep tightly closed under dry inert gas (nitrogen/argon). Store in a desiccator or with molecular sieves to minimize hydrolysis. Use amber glass to reduce light‑induced discoloration.
  • After opening, consider aliquoting into septum‑cap vials and backfilling with inert gas to limit headspace moisture.
  • Do not refrigerate in high‑humidity environments without secondary containment; moisture ingress will degrade the reagent.

• Shipping

  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

• Reconstitution

  • Neat liquid; no reconstitution required. For solution handling, prepare stock solutions in dry DCM, toluene, or THF immediately before use. Verify dryness by Karl Fischer when reactions are moisture‑sensitive.

• Shelf life

  • Not specified for this item; refer to CoA/Spec Sheet. Monitor by 1H NMR/IR (disappearance of acyl chloride band near ~1790 cm−1; literature) to assess integrity over time.

Structure and Identity

S-(4-Chlorophenyl) chlorothiolformate is an S‑aryl chlorothioformate of the general type ClC(=O)–S–Ar, bearing a para‑chloro substituent on the phenyl ring.

• Item identifiers (from Product Data)
  • CAS: 13606-10-5
  • PubChem CID: 637671
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/computed identifiers (non-specification, for reference)
  • Typical molecular formula (literature): C7H4Cl2OS
  • Typical molecular weight (literature): ~207.07 g/mol
  • Representative SMILES (literature): Clc1ccc(cc1)SC(=O)Cl
• Structural features (general description)
  • Functional groups: acyl chloride (–C(=O)Cl) conjugated to a thioether sulfur (–S–Ar); para‑chloro phenyl ring.
  • Connectivity: carbonyl carbon double‑bonded to oxygen and single‑bonded to chlorine; carbonyl carbon also bonded to sulfur which is bound to the 4‑chlorophenyl ring (para substitution on the ring).
  • 2D depiction in words: a benzene ring bearing Cl at the para position; the ipso carbon is connected via sulfur to a carbonyl carbon that bears a chlorido substituent (Cl–C(=O)–S–C6H4–Cl(p)).
  • Stereochemistry: none (achiral).

Synthetic Utility

Functional group and reactivity profile:

• Electrophilic carbonyl center (acyl chloride) adjacent to sulfur confers high reactivity toward O‑ and N‑nucleophiles, producing thiocarbonates (ROCO–SAr) and carbamothioates (RNCO–SAr) under mild conditions.
• The S‑aryl group stabilizes the leaving group and can modulate reactivity and downstream transformability (e.g., reductive cleavage to thiol or exchange with other nucleophiles).

Representative transformations (literature, non‑specification):

• Alcohol to thiocarbonate: ROH + base (Et3N/DMAP) + ArSCOCl → ArSCOOR. Cyclic thiocarbonates from 1,2‑ or 1,3‑diols are accessible and serve as handles for eliminations or deoxygenations.
• Amine to carbamothioate: RNH2 + ArSCOCl (0–5 C to rt) in DCM/THF with base gives RNHC(O)SAr derivatives useful as protecting or activating groups.
• Further elaboration: Thiocarbonates can undergo reduction (e.g., with LiAlH4 or boranes), radical processes, or substitution to unveil alcohols/thiols in orthogonal sequences.

Selectivity considerations

• Competes with water, alcohols, and amines; order of addition and base choice govern chemoselectivity in polyfunctional substrates.
• DMAP catalysis accelerates O‑acylation over N‑acylation in mixed systems; for amine selectivity, use sterically hindered, non‑nucleophilic bases (DIPEA) and low temperature.

Target Specificity

Not applicable. This product is a small‑molecule synthetic reagent and is not an antibody, probe, or biologic. No antigen/epitope, species reactivity, clone, or isotype information is relevant or provided.