Thiomorpholine, 3-methyl-, 1,1-dioxide - ≥95% , CAS No.148761-50-6

CAS: 148761-50-6 Cat. No.: T1003245 Summenformel: C₅H₁₁NO₂S Molekulargewicht: 149.21 PubChem CID: 14953855

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥95%

Storage

Room temperature

Reinheit

≥95%

Namen und Kennungen

Kanonisches Lächeln

CC1CS(=O)(=O)CCN1

IUPAC Name

3-methyl-1,4-thiazinane 1,1-dioxide

InChIKey

QLCHHQQTWDDARM-UHFFFAOYSA-N

INCHI

1S/C5H11NO2S/c1-5-4-9(7,8)3-2-6-5/h5-6H,2-4H2,1H3

Isomere SMILES

CC1CS(=O)(=O)CCN1

PubChem CID

14953855

Molekulargewicht

149.21

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Klasse Thiazinanes
      • Subclass Thiomorpholines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Thiazinanes
• Subclass: Thiomorpholines
• Intermediate Tree Nodes: Not available
• Direct Parent: Thiomorpholines
• Alternative Parents: Sulfones Dialkylamines Azacyclic compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aliphatic heteromonocyclic compounds
• Substituents: 1,4-thiazinane - Sulfone - Azacycle - Secondary amine - Secondary aliphatic amine - Organic nitrogen compound - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organonitrogen compound - Amine - Aliphatic heteromonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as thiomorpholines. These are heterocyclic compounds containing a thiomorpholine ring, which is a six-membered aliphatic ring containing one nitrogen atom and one sulfur atom at positions 1 and 4 respectively, and four carbon atoms.
• 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 149.210 g/mol
• XLogP3: -0.600
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 149.051 Da
• Monoisotopic Mass: 149.051 Da
• Topological Polar Surface Area: 54.600 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 180.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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 manufacturer-tested bioassay protocols are provided for this item. As a synthetic building block, usage protocols are reaction-specific.
• For synthetic operations, see the Reaction Conditions tab for general procedures (N-alkylation, acylation, reductive amination). Adapt stoichiometry, solvent, and temperature to the reactivity of your coupling partners and consult primary literature for analogous substrates.

Biological Roles

• Applicability: This compound is a synthetic, non-natural heterocycle. It does not have known endogenous biological roles.
• Research context (general, non-clinical):
  • The thiomorpholine-1,1-dioxide motif is used in medicinal chemistry as a highly polar, hydrogen-bonding ring to improve aqueous solubility and modulate basicity. Incorporation as a side chain or as part of cationic centers can influence permeability and metabolic soft spots.
  • The secondary amine permits formation of salts for in vitro assay compatibility across a range of pH values, aiding screening campaigns. The sulfone contributes strong dipole character and can affect binding interactions as an H-bond acceptor.
• No medical or therapeutic claims are made. For research use only (per Product Data). Any biological evaluation should be designed, executed, and interpreted by qualified professionals following institutional safety and ethical guidelines.

Buffer Applications

• Not typically used as a buffering agent. While it contains a secondary amine capable of protonation, dedicated laboratory buffers (e.g., phosphate, acetate, HEPES, MOPS) offer defined pKa values and superior buffering capacity.
• If present in aqueous media, it may modestly affect pH via protonation/deprotonation, but it should not replace established buffer systems. Select a proper buffer based on your pH target and ionic strength requirements.

Green Alternatives

• Context: As a polar heterocyclic amine reagent, this item is not a process solvent. “Greener alternatives” therefore relate to greener reaction media and operations when employing this compound.
• Greener solvent choices (literature guidance):
  • Prefer water, ethanol, isopropanol, or ethyl acetate where compatible. Many N-acylations and reductive aminations can be conducted in aqueous ethanol or EtOH/AcOEt biphasic systems.
  • For polar aprotic needs, consider Cyrene, propylene carbonate, or dimethyl carbonate as partial substitutes for DMF/DMSO/MeCN, subject to solubility and reactivity constraints.
• Workup and purification:
  • Utilize salt formation/crystallization to avoid chromatographic silica waste when possible (e.g., isolate as HCl salt, then free-base).
  • Apply reverse-phase chromatography with water-rich mobile phases to reduce organic solvent consumption.
• Energy and safety:
  • Many transformations with this amine proceed at ambient to moderate temperatures due to its high intrinsic nucleophilicity; avoid unnecessary heating.
• Trade-offs:
  • Water/ethanol media may slow SN2 alkylations or increase competing hydrolysis; polar green solvents can alter selectivity. Pilot on small scale and adjust base/catalyst accordingly.

Pharmaceutical Uses

• No pharmacopeial or excipient grade is specified for this item.
• General formulation context (non-clinical, research only):
  • The secondary amine allows salt formation (e.g., hydrochloride, mesylate), which can be leveraged for model formulation studies or as an intermediate toward drug-like molecules.
  • The ring sulfone increases polarity and may be used to tune solubility/permeability profiles in lead optimization. However, this listing is not intended for human or veterinary use.
• Regulatory note: For research use only (per Product Data). Not for use in diagnostic or therapeutic applications. If pursuing GMP or clinical pathways, source compliant material and conduct full quality/regulatory assessments.

Physical Properties

• Item-specific specs: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/computed expectations for 3-methylthiomorpholine 1,1-dioxide (qualitative, not item specifications):
  • Physical state/appearance: Typically a low-melting solid or high-boiling viscous liquid for analogous ring sulfones; exact form depends on isomer/purity.
  • Polarity: High polarity due to one secondary amine and one sulfone; strong hydrogen-bond acceptor; one H-bond donor at nitrogen.
  • Solubility: Expected to be highly soluble in water and polar protic/aprotic solvents (MeOH, EtOH, acetone, acetonitrile, DMSO); diminished solubility in nonpolar hydrocarbons (hexanes, toluene).
  • Acid–base: Basic secondary amine with lowered basicity relative to morpholine; conjugate-acid pKa typically in the ~5–7 range (literature trend for sulfone-embedded amines; value depends on substitution). Forms water-soluble salts with mineral/organic acids.
  • Partitioning: Low logP/logD at neutral pH (qualitatively hydrophilic relative to morpholine), enhanced by salt formation in acidic media.
  • Boiling/melting points, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet. For method development or handling, determine exact values from the CoA/SDS or measure under your lab conditions.
• Practical note: Hygroscopicity may be moderate due to polar functionality; cap promptly and purge headspace if long-term precision weighing is required.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Interpreting typical grades for this compound class (general guidance):
  • Research-grade or ≥95–98% purity is customary for heterocyclic amine building blocks; higher grades minimize side reactions (e.g., N-oxidation or residual solvents) and improve reproducibility in medicinal chemistry.
  • If supplied as an acid salt (e.g., HCl), residual inorganic content is expected; free-base material prioritizes low water and low nonvolatile residues for stoichiometric accuracy. Confirm salt form on the CoA.
  • For chromatography-intensive applications, low-UV-absorbing residuals and defined water content are beneficial. If anhydrous claims are required, verify Karl Fischer on the CoA.
• Stabilizers/additives: None specified for this item. For amine-containing materials, stabilizers are typically unnecessary; however, inert-atmosphere packaging can help maintain assay for long storage.
• Batch documentation: Request CoA with full assay, identity (NMR/IR/HRMS), residual solvents, and water content if your application is sensitive. When scaling up, consider lot-to-lot verification via quick NMR (check for salt vs free base) and melting range (if solid).

Reaction and Applications

• Role in synthesis (general for 3-methyl thiomorpholine-1,1-dioxide; literature-based):
  • N-nucleophile: Undergoes N-alkylation (SN2 with alkyl halides/mesylates/tosylates) to furnish tertiary amines bearing a polar sulfone-containing ring.
  • Acylation/sulfonylation: Reacts with acyl/sulfonyl chlorides or activated esters to form amides/sulfonamides; useful for installing basic polar side chains in medicinal chemistry.
  • Salt formation: Readily forms crystalline salts (e.g., HCl, p-TsOH), aiding purification and modulating solubility for formulation studies.
  • Reductive amination (on external carbonyls): Serves as the amine partner with aldehydes/ketones using NaBH3CN/NaBH(OAc)3 or catalytic hydrogenation to access N-substituted analogs.
• Influence of the sulfone: The embedded sulfone increases polarity and reduces amine basicity relative to morpholine/piperidine, often improving aqueous solubility and metabolic stability of target molecules. The sulfone is typically inert under many reaction conditions, surviving bases, oxidants, and hydrogenation that would affect thioethers.
• Practical tips:
  • Base choice: K2CO3, Cs2CO3, or DIPEA for alkylations; stronger bases (NaH) only if necessary and in dry aprotic media. Monitor for over-alkylation.
  • Protecting strategies: If selective functionalization elsewhere is desired, protect the amine (e.g., Boc, Cbz); the sulfone is non-nucleophilic and generally doesn’t require protection.
  • Workup: Amine salts partition to aqueous phase; free-base by basification (pH ~10) and extract into polar organics (EtOAc, i-PrOAc).

Reaction Conditions

• Typical conditions (literature guidance; adjust per substrate):
  • N-alkylation (SN2): 1.0–1.5 equiv amine, 1.0 equiv alkyl halide/mesylate, K2CO3 or Cs2CO3 (2–3 equiv) in MeCN, DMF, or acetone, 20–50 °C, 2–16 h. Suppress over-alkylation by using slight amine excess and monitoring by TLC/LC–MS.
  • Reductive amination: Carbonyl (1.0 equiv), amine (1.2–2.0 equiv), NaBH(OAc)3 (2–3 equiv) in DCE/MeOH or AcOH/MeCN at 20–25 °C, 4–18 h; or catalytic hydrogenation (H2, Pd/C) of preformed imines in EtOH under mild pressure.
  • Acylation/sulfonylation: Acid chloride/sulfonyl chloride (1.0–1.2 equiv), amine (1.0 equiv), base (DIPEA, TEA, or NaHCO3) in DCM, THF, or MeCN, 0–25 °C, 1–6 h. Add catalyst DMAP as needed for sluggish acylations.
  • Carbamate/urea formation: Use CDI or triphosgene equivalents with the amine in THF/MeCN, 0–25 °C; quench and isolate as needed.
• Compatibility notes:
  • The sulfone group withstands hydrogenation and many oxidative workups; avoid very strong nucleophiles or reductants that could target the sulfone under forcing conditions.
  • Water/EtOH cosolvents often acceptable and greener; ensure base solubility.
• Workup/purification:
  • Salt switching facilitates separation from neutral or acidic byproducts. Reverse-phase chromatography with aqueous modifiers (0.1% TFA or formic acid) improves peak shape for basic products.
• Expected yields: Reaction-class typical isolated yields range from 60–90% depending on substrate electronics and sterics (literature ranges; optimize per case).

Safety and Handling

• Item-specific hazard data (from Product Data):
  • GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
• General safety guidance for secondary amine sulfones (literature/industry practice; not product-specific):
  • Likely hazards: May cause skin/eye irritation; amines can be irritating to respiratory tract. Avoid inhalation of vapors/aerosols and contact with skin/eyes.
  • PPE: Safety glasses or face shield, lab coat, appropriate chemical-resistant gloves (e.g., nitrile). Work in a fume hood when handling neat material or during reactions.
  • First aid overview: In case of contact, rinse skin/eyes with water for ≥15 minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical attention. Always follow your institutional procedures and the SDS.
  • Incompatibilities: Strong oxidizers (further N-oxidation possible), strong acids/bases (salt formation or degradation), acylating/alkylating agents (reactive at the amine). Avoid reactive carbonyls if unintended derivatization is a concern.
  • Stability: Sulfone is generally oxidation-stable; protect the secondary amine from moisture/CO2 if free-base properties matter for stoichiometry. No special peroxide risks (non-ether).
  • Fire safety: Organic combustible; use standard extinguishing media (CO2, dry chemical, foam). Thermal decomposition may release nitrogen/sulfur oxides.
• Always consult the product-specific SDS for authoritative hazard classification and response measures.

Solvent Selection

• Applicability: This product is a polar heterocyclic amine sulfone reagent, not a process solvent. Solvent selection pertains to dissolving/processing it or using it in synthesis.
• Polarity/miscibility (literature-based behavior for amine sulfones):
  • Highly soluble in water and polar organic solvents (MeOH, EtOH, i-PrOH, acetonitrile, acetone, DMF, DMSO).
  • Limited solubility in nonpolar media (hexanes, cyclohexane); moderate in moderately polar aromatics (toluene) when warmed or as acid salts.
• Practical choices by task:
  • Salt formation and bioconjugation-friendly work: water or aqueous alcohols; buffer at pH 5–7 to maintain partial protonation and solubility without over-acylating the amine.
  • N-alkylation/N-acylation: polar aprotic solvents (DMF, DMSO, MeCN) or alcohols (MeOH, EtOH) with base; ensure dryness if using strong bases.
  • Purification: Reverse-phase preparative HPLC or flash on polar stationary phases; elute with water–MeCN (0.1% acid modifier improves peak shape for the amine).
• Comparison (qualitative):
  • Versus morpholine: More polar (due to sulfone) and typically less basic; often more water soluble at neutral pH.
  • Versus piperidine: Far less basic; markedly higher polarity; different reactivity profile in alkylation/acylation campaigns.

Storage and Reconstitution

• Item-specific storage (from Product Data): Store at room temperature.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• General handling:
  • Keep container tightly closed. Store in a dry place away from strong acids/bases and oxidizers. For long-term storage, a desiccator and inert gas headspace are prudent for amines.
  • If provided as a free base, material may absorb CO2/H2O; recap promptly after use.
• Reconstitution/dissolution (general guidance):
  • Highly soluble in polar media. To prepare stock solutions for synthetic use, dissolve in water, methanol, ethanol, acetonitrile, DMF, or DMSO as appropriate for your application.
  • For aqueous stocks, adjust pH with dilute HCl to form the ammonium salt for enhanced stability/solubility; for organic stocks, ensure anhydrous solvent if moisture-sensitive couplings are planned.
  • Typical working concentrations: 0.1–1.0 M in organic solvents for coupling operations; for bioassay research, prepare fresh as needed and filter sterilize if required by protocol (non-sterile product; research use only).
• Freeze–thaw: Not generally required. If preparing long-term solutions, consider aliquoting and storing at 2–8 °C or −20 °C, protected from moisture; verify stability experimentally before scale-up.

Structure and Identity

• Item-specific (from Product Data):
  • Product name: Thiomorpholine, 3-methyl-, 1,1-dioxide (SKU: T1003245)
  • CAS: 148761-50-6; PubChem CID: 14953855
  • InChIKey: 299826 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/literature (general chemical identity of this structure):
  • Common structural description: A six-membered saturated heterocycle containing one secondary amine nitrogen and one sulfur atom oxidized to a sulfone (S(=O)2). The ring bears a methyl substituent at C-3 (vicinal to the sulfone sulfur and the ring CH2), giving a 3-methyl thiomorpholine-1,1-dioxide.
  • Functional groups: secondary amine (–NH–), sulfone (–S(=O)2–) embedded in the ring; one alkyl (methyl) substituent.
  • Stereochemistry: 3-methyl substituent can adopt chair conformations; no stereocenter unless ring substitution pattern/context induces it (racemic conformers in solution).
  • Likely empirical formula (for the neutral free base, literature/computed): C5H11NO2S.
  • Approximate formula weight (literature/computed): ~149.21 g/mol.
• 2D verbal depiction: A chair-like six-membered ring with N at position-1 (secondary amine H), CH2 at C-2, a methyl-substituted carbon at C-3 (–CH(CH3)–), CH2 at C-4, CH2 at C-5, and S at position-6 bearing two double-bonded oxygens (sulfone). The N and S occupy para positions across the ring.

Synthetic Utility

• Functional handles:
  • Secondary amine: amenable to alkylation, acylation, sulfonylation, carbamate formation, urea formation (via phosgene equivalents or CDI), and reductive amination.
  • Ring sulfone: chemically robust; sustains many oxidative and basic conditions; contributes to polarity and conformational effects without participating directly in nucleophilic chemistry.
  • 3-Methyl substitution: introduces defined steric bias; can impact regioselectivity in N-functionalization and downstream coupling reactions.
• Applications:
  • Fragment-to-lead programs seeking increased aqueous solubility while retaining a basic center.
  • Installation as a solubilizing appendage on aryl/heteroaryl cores via N-linkage.
  • Preparation of quaternary ammonium salts (via exhaustive alkylation) for phase-transfer catalysis studies or ion-pairing controls.
• Retrosynthetic considerations:
  • The amine can serve as a nucleophile onto activated electrophiles (acid chlorides, chloroformates, sulfonyl chlorides, alkyl halides). Protect if orthogonal reactivity is required elsewhere in the molecule.
  • Salt toggling (free base ↔ acid salt) can streamline isolation and handling, and can be exploited to switch between organic and aqueous phases during multistep sequences.

Target Specificity

• Not applicable. This product is a small-molecule reagent/building block, not a biological targeting reagent (e.g., antibody, ligand standard with defined biomolecular target). No target specificity information is provided in the Product Data.