This compound belongs to the class of organic compounds known as alpha amino acids. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).
External Descriptors
thiomorpholinemonocarboxylic acid
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.
Certificati (CoA, COO, BSE/TSE e tabella di analisi)
C of A & Other Certificates(BSE/TSE, COO):
Analytical Chart:
Proprietà chimiche e fisiche
Peso molecolare
147.200 g/mol
XLogP3
-2.400
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
1
Exact Mass
147.035 Da
Monoisotopic Mass
147.035 Da
Topological Polar Surface Area
74.600 Ų
Heavy Atom Count
9
Formal Charge
0
Complexity
118.000
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
Calcolatori di soluzioni
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Recensioni
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Application Protocols
No assay-specific protocols are validated for this small-molecule reagent.
General handling suggestions (literature/practice):
Stock solutions: prepare in DMSO (e.g., 100–500 mM) or water/aqueous buffer after pH adjustment. Filter-sterilize (0.22 µm) if sterility is required.
Amide coupling setup: dry glassware/solvents; use 1.1–1.5 equiv coupling reagent and 2–4 equiv tertiary amine base; monitor by TLC or LC–MS.
Oxidation to sulfoxide/sulfone: add oxidant slowly at low temperature; monitor by LC–MS to control oxidation state; quench excess oxidant and extract under conditions that maintain the desired ionization state.
For any specialized application, develop and validate an internal SOP. Consult primary literature and the product’s CoA/SDS for compatibility and safety.
Biological Roles
Item-specific biological roles are not established; this product is provided for research use only.
General/literature context:
Thiomorpholine motifs are common heterocyclic fragments in medicinal chemistry, serving as polar, conformationally restricted, and metabolically tunable ring systems. The thioether can be oxidized in vivo (sulfoxide/sulfone) and the ring nitrogen is protonatable, influencing ADME properties.
Carboxylic acid substitution at the 3-position introduces a strong acid handle with potential for ionic interactions, transporter recognition, and salt formation. In biochemical assay development, such acids can be converted to amides/esters to modulate permeability and target engagement.
As a standalone small molecule, thiomorpholine-3-carboxylic acid may act primarily as a synthetic intermediate rather than a bioactive agent; any biological evaluation should be designed and interpreted within controlled research settings, without assumptions of pharmacological activity.
Note: No clinical or therapeutic uses are claimed or implied. For biological testing, prepare solutions under sterile conditions as needed, verify endotoxin/bioburden if required for your workflow, and document pH/ionic strength to manage zwitterionic behavior.
Buffer Applications
This compound is not a standard buffering agent and is not typically used to prepare classical biological buffers.
Guidance (general):
With both an amine (basic) and a carboxylic acid (acidic), thiomorpholine-3-carboxylic acid can exist as a zwitterion, but its pKa values and buffer capacity ranges are not optimized or standardized for buffering applications.
If used experimentally as a bespoke buffer component or counterion, determine precise pKa values by potentiometric titration and construct a Henderson–Hasselbalch profile to target appropriate pH windows. Validate ionic strength and compatibility with metals (thioether is a soft donor and can weakly coordinate certain metals).
For robust, validated buffering, choose established systems (e.g., phosphate, HEPES, MOPS) unless there is a specific rationale to incorporate this heterocycle.
Green Alternatives
Opportunities to improve sustainability when working with thiomorpholine-3-carboxylic acid center on solvent and reagent choices rather than replacing the heterocycle.
Greener choices (literature/guidelines):
Solvents:
Favor water, ethanol, or isopropanol where feasible (e.g., crystallizations, salt switches, some esterifications under catalytic conditions).
Replace DMF/NMP with safer polar aprotics when possible (acetonitrile, 2-MeTHF, Cyrene, propylene carbonate), mindful of solubility and coupling efficiency.
Use 2-MeTHF or CPME instead of DCM/THF for extractions and some couplings; check stability toward bases/acids.
Coupling reagents:
Consider DMTMM or CDI as lower-hazard alternatives to HATU/HBTU; minimize hazardous byproducts.
Enzymatic or catalytic amidations in aqueous media (boronic acid catalysis, 1,1′-carbonyldiimidazole in water) can reduce solvent and waste.
Oxidations of sulfur:
Employ H2O2/acetic acid or Oxone for sulfoxide/sulfone formation where selectivity allows, in place of peracids.
Tradeoffs (general):
Greener solvents may reduce solubility; mild heating, co-solvents, or in situ salt formation can compensate.
Some green coupling systems give slower rates or lower conversions with sterically hindered partners—optimize base, temperature, and concentration.
Small comparison (general):
DMF/HATU (traditional): high reactivity, poor EHS profile.
MeCN or 2-MeTHF with DMTMM/CDI (greener): improved EHS, may require longer times or slightly elevated temperatures.
Pharmaceutical Uses
No pharmacopeial monograph or excipient designation is provided for this item; it is offered for research use only.
General/literature context:
Role as a building block: Thiomorpholine-3-carboxylic acid is valuable for the preparation of amide-linked thiomorpholine derivatives, common motifs in medicinal chemistry for tuning solubility, basicity, and metabolic profile.
Salt formation and crystallization studies: The acid function enables formation of pharmaceutically acceptable salts (e.g., sodium, tromethamine) of downstream derivatives; the ring nitrogen can also form acid addition salts in intermediates.
Pre-formulation research: The zwitterionic nature can be leveraged in model studies of permeability or as a polar fragment in fragment-based drug discovery (FBDD) to probe binding hotspots when converted to amides/esters.
Compliance and handling:
No therapeutic or diagnostic claims are made. If used in drug discovery workflows, ensure material traceability (CoA, batch records) and assess residual solvents, water content, and elemental impurities per ICH Q3 standards as appropriate for the stage of development.
Physical Properties
Item-specific physicochemical specifications (grade-specific assays, exact mp/bp, UV cutoff, residuals): Not specified for this item; refer to CoA/Spec Sheet.
General/literature physicochemical information (for guidance only):
Aggregate state: typically a crystalline solid (zwitterionic amino-thio carboxylic acid, literature/generic behavior).
Acid–base properties: bifunctional; expected to exist as a zwitterion near neutral pH. Typical pKa values for related thiomorpholine carboxylic acids: pKa1 (carboxyl) ~2–4; pKa2 (conjugate acid of ring N) ~8–10 (literature ranges; consult primary data for exact values).
Polarity: high; contains –CO2H and a ring nitrogen; logP expected to be low; often shows good aqueous solubility in its salt or zwitterionic form (literature/general).
Solubility (qualitative, literature): soluble to highly soluble in water (especially as the sodium/potassium salt), methanol, ethanol, and polar aprotic solvents such as DMSO; poorly soluble in nonpolar hydrocarbons.
Functional group handles: secondary amine (basic), thioether (soft donor, oxidizable), carboxylic acid (acidic, activatable for coupling).
Note: Actual, lot-specific physical constants and chromatographic purity should be confirmed from the Aladdin CoA/SDS for SKU T168518.
Quality and Grades
Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
Guidance on grades (general):
Research grade: suitable for most synthetic and screening workflows. Purity is typically expressed by HPLC/GC/quantitative NMR where applicable.
Low-residual solvent/heavy metals specifications, water content, and chromatographic purity thresholds vary by grade. Because this product’s specific limits are not listed here, consult the CoA for assay methodology (e.g., HPLC area%, 1H NMR) and impurity profile.
Stabilizers: none indicated in Product Data. For heterocycles containing thioethers, stabilizers are generally unnecessary if stored dry; verify absence/presence on the CoA.
Practical notes:
If coupling to sensitive amines/alcohols, verify acid content and residual inorganic salts prior to use (they can influence coupling efficiency and chromatograms).
For medicinal chemistry, consider documenting batch ID/CoA and repeating key assays (1H/13C NMR, HRMS, water content by KF) to ensure reproducibility across SAR campaigns.
Reaction and Applications
As a heterocyclic carboxylic acid with a thioether and secondary amine, thiomorpholine-3-carboxylic acid is a versatile building block in synthesis, fragment libraries, and ligand design.
Amide/urea/ester formation: activate the acid (EDC·HCl/HOBt, HATU/DIPEA, DIC/Oxyma, CDI) to couple with amines or alcohols. The ring nitrogen can be protected (e.g., Boc) if chemoselectivity is required.
Sulfur oxidation: selective oxidation to sulfoxide (1 equiv m-CPBA, 0 to rt) or sulfone (excess oxidant) tunes polarity and hydrogen-bond acceptor strength, altering physicochemical properties.
N-alkylation/acylation: ring N can undergo alkylation (e.g., RI/K2CO3 in polar aprotic solvents) or acylation to give amides/carbamates; Boc protection followed by downstream transformations is common.
Decarboxylative strategies: activation as NHPI ester enables photoredox decarboxylative couplings (e.g., to aryl/alkyl radicals) to access C–C bonded thiomorpholine derivatives.
Cross-coupling adjunct: convert to the corresponding acid chloride (oxalyl chloride, catalytic DMF) to access thioamide/amide derivatives of complex scaffolds.
Salt formation/ion-pairing: prepare hydrochloride or mesylate salts to modulate solubility and crystallinity for purification or formulation studies.
Practical tips:
Control pH during aqueous workups; zwitterionic species can oil out near the isoelectric point.
For amide couplings, pre-form the carboxylate with mild base (DIPEA) and use minimal DMF to maintain solubility; avoid strong oxidants unless sulfur oxidation is desired.
If N-alkylation competes, protect N (Boc or Cbz) prior to activating the acid.
Reaction Conditions
General literature guidance for common transformations of thiomorpholine-3-carboxylic acid (optimize per substrate):
Amide coupling:
HATU (1.1–1.5 equiv), DIPEA (2–4 equiv), DMF or MeCN, 0–25 °C, 0.5–4 h; typical conversions high with minimally hindered amines.
EDC·HCl (1.2–1.5 equiv) + Oxyma/HOBt (1.1–1.5 equiv), DIPEA (2–3 equiv), DMF or DCM/DMF, 0–25 °C; monitor for O-acylurea byproducts; Oxyma preferred for safety.
DMTMM (1.1–1.5 equiv) in MeOH, MeCN, or water, rt to 40 °C, 1–6 h; convenient for alcohols and amines.
Esterification:
Steglich: DCC (1.2 equiv), DMAP (0.1 equiv), DCM, 0–25 °C; or Fischer in anhydrous ROH with catalytic H2SO4, reflux.
Sulfur oxidation:
To sulfoxide: m-CPBA (1.0–1.2 equiv), DCM, 0–5 °C to rt, 1–3 h; or H2O2/acetic acid, 0–25 °C (longer times).
To sulfone: m-CPBA (≥2 equiv) or Oxone (excess), MeOH/H2O, 25–50 °C.
Acid chloride formation:
Oxalyl chloride (1.5–2 equiv), cat. DMF, DCM, 0 °C → rt, 1–3 h; trap with amine or alcohol in situ.
N-protection (Boc):
Boc2O (1.1–1.5 equiv), Na2CO3 or DIPEA, dioxane/H2O or MeCN, 0–25 °C; deprotect with TFA/CH2Cl2 at 0–25 °C.
Decarboxylative coupling (via NHPI ester):
DIC (1.2 equiv), NHPI (1.2 equiv), DMAP (cat.), DCM, rt → irradiate (blue LED) with photocatalyst (e.g., Ir or organic dyes) for radical coupling to alkenes/arenes.
Notes:
Control pH and counterions to manage solubility. Zwitterions may precipitate around the isoelectric point; employ co-solvents or salts.
Avoid strong oxidants unless intentional, to prevent unplanned S-oxidation during coupling/activation.
Safety and Handling
Hazard classification for this specific item: Not specified for this item; refer to SDS.
General safety considerations for heterocyclic carboxylic acids (literature/practice):
Expected hazards: may cause skin/eye irritation; dust may irritate respiratory tract. Not volatile; low inhalation risk under normal handling, but avoid aerosols and dust formation.
PPE: laboratory coat, safety glasses or splash goggles, and suitable chemical-resistant gloves (e.g., nitrile). Use in a well-ventilated area or fume hood when weighing/pulverizing.
First aid (overview):
Eye contact: rinse cautiously with water for several minutes; remove contact lenses if present; seek medical attention if irritation persists.
Skin contact: wash with soap and water; remove contaminated clothing.
Inhalation: move to fresh air; seek medical attention if symptoms occur.
Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
Incompatibilities: strong oxidizing agents can over-oxidize the thioether; strong bases/acids will change ionization state (affecting solubility). Oxidants (e.g., peracids) intentionally oxidize S to sulfoxide/sulfone—avoid unintended exposure.
Thermal stability: generally stable at ambient conditions; avoid excessive heat during drying to prevent decomposition.
Always consult the Aladdin SDS for SKU T168518 for authoritative hazard statements (H‑phrases), pictograms, and emergency procedures.
Solvent Selection
Thiomorpholine-3-carboxylic acid is a polar, bifunctional heterocycle; solvent choice hinges on ionization state and downstream transformation.
Aqueous systems: water and aqueous buffers solubilize the zwitterion or salts well. Adjust pH (≥8) to form the carboxylate for enhanced solubility; acidify to pH ≤3 to favor the neutral acid (reduced solubility).
Polar protic: methanol, ethanol, isopropanol dissolve the neutral/zwitterionic form moderately to well; useful for crystallizations and salt formation.
Polar aprotic: DMSO and DMF offer excellent solvating power for stock solutions (e.g., 0.1–1.0 M) prior to dilution into aqueous media or for peptide-style couplings.
Nonpolar/medium polarity: limited solubility in EtOAc, MTBE, toluene, and alkanes; employ ion pairing or convert to esters for work in low-polarity media.
When to choose which:
Amide coupling: DMF, NMP, or DCM/DMF mixtures with carbodiimides or uronium reagents.
Salt screening/crystallization: ethanol or isopropanol with stoichiometric acid/base.
Biological assay stock: prepare concentrated DMSO stock, then dilute into buffer; monitor pH to avoid precipitation near the isoelectric point.
Comparison (general):
Versus morpholine-3-carboxylic acid: slightly lower basicity at N and higher polarizability due to sulfur; similar solubility trends.
Versus non-heterocyclic acids: markedly greater water/DMSO solubility from the embedded amine.
Storage and Reconstitution
Storage conditions: Room temperature (Product Data). Protect from moisture; store tightly capped in a desiccator if possible to maintain assay and handling consistency. Avoid prolonged exposure to light and oxidizing atmospheres to limit undesired sulfur oxidation.
Shipping: Shipped under normal conditions (Product Data).
Stability: Generally stable as a dry solid at ambient temperature under inert/closed conditions. For long-term storage, consider cool, dry conditions and minimize headspace oxygen.
Reconstitution and solution handling (general):
Solubility: readily soluble in DMSO; often soluble in water upon pH adjustment (e.g., to pH ≥ 8 to form the carboxylate). Ethanol/methanol can also be used for intermediate polarity.
Preparing aqueous solutions: adjust pH with NaOH or suitable base to dissolve to target concentration; back-titrate if a specific pH is needed. Filter through 0.22 µm for clarity/sterility.
Working solutions: prepare fresh when possible. If storage is required, aliquot and keep at 2–8 °C; avoid repeated freeze–thaw of aqueous stocks to prevent microbial growth and pH drift.
Note: Item-specific specifications (water content, assay, impurities) are Not specified for this item; refer to CoA/Spec Sheet. Research use only.
Structure and Identity
Thiomorpholine-3-carboxylic acid is a saturated six‑membered heterocycle (1,4-thiazinane) bearing a carboxylic acid substituent at the 3-position, adjacent to both the ring sulfur and nitrogen. The ring contains one tertiary thioether sulfur and one secondary amine nitrogen, enabling zwitterionic forms.
CAS: 20960-92-3 (Product Data)
PubChem CID: 440159 (Product Data)
InChIKey: 165836 (Product Data)
Molecular formula: C5H9NO2S (literature)
Molecular weight: ~147.19 g/mol (literature, from formula)
SMILES: O=C(O)C1CSCCN1 (literature; representative tautomeric/positional forms may exist)
Structural features (descriptive):
Six-membered ring containing alternating –CH2– units with a thioether sulfur (S) and a secondary amine nitrogen (N) across the ring (1,4 relationship).
A carboxylic acid (–CO2H) at C-3, allylic to both heteroatoms, enabling intramolecular H-bonding and zwitterionic resonance forms (–NH+/–COO−) depending on pH.
No stereogenic centers in the parent scaffold (as drawn); planar carboxylate and chair-like ring conformations dominate.
Identifiers and synonyms (general):
Also referred to in the literature as 3-carboxythiomorpholine; 3-thiomorpholinecarboxylic acid; thiomorpholine-3-acetic acid is a different entity (avoid confusion).
Synthetic Utility
Key functional elements of thiomorpholine-3-carboxylic acid enable diverse, chemoselective transformations:
Carboxylic acid handle:
Amide coupling to primary/secondary amines (EDC/HOBt or Oxyma; HATU/DIPEA; DMTMM in MeOH/H2O) provides rapid access to amide-linked libraries.
Esterification (Fischer, Steglich) to modulate lipophilicity or serve as pro-moieties.
Conversion to acyl chlorides/anhydrides for advanced acyl transfer chemistry.
Secondary amine:
N-protection (Boc, Cbz) to direct chemoselectivity during acid activation; deprotection under standard conditions (TFA for Boc, hydrogenolysis for Cbz).
N-alkylation or reductive amination after prior protection of the acid as an ester or via phase separation strategies.
Thioether sulfur:
Oxidation to sulfoxide/sulfone to adjust electronics and polarity without changing ring size.
S-alkylation under strong electrophiles affords sulfonium salts, useful intermediates for downstream substitution/elimination.
Decarboxylative functionalization:
NHPI/HOAt active esters enable photoredox or nickel-catalyzed decarboxylative C–C and C–heteroatom couplings, facilitating late-stage diversification of the ring carbon bearing the acid.
Strategic value:
Acts as a polar, conformationally restricted synthon to replace flexible aminoalkyl chains; the 3-carboxy substitution offers a handle orthogonal to N-functionalization for rapid SAR exploration.
Target Specificity
Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or affinity reagent. No antigen/epitope specificity, species reactivity, or isotype information applies.
Domande frequenti
What is the purity of this product?
This product is supplied at ≥95% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.
How should this product be stored?
Store at room temperature.
How is this product shipped?
This product ships under standard ambient conditions. No temperature-controlled packaging is required.
What are the CAS number, molecular formula and molecular weight?
The CAS Number is 20960-92-3, the molecular formula is C5H9NO2S, and the molecular weight is 147.2 g/mol. InChIKey JOKIQGQOKXGHDV-UHFFFAOYSA-N.
What documentation is provided?
Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.
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