2-Ethylbenzene-1-sulfonamide - ≥97% , CAS No.85-92-7

CAS: 85-92-7 Cat. No.: E1024379 Summenformel: C₈H₁₁NO₂S Molekulargewicht: 185.250 EG-Nummer: 178-210-8

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥97%

Storage

Room temperature

Reinheit

≥97%

Namen und Kennungen

• Kanonisches Lächeln: CCC1=CC=CC=C1S(=O)(=O)N
• IUPAC Name: 2-ethylbenzenesulfonamide
• InChIKey: NMBWXBWFDHVLGS-UHFFFAOYSA-N
• INCHI: 1S/C8H11NO2S/c1-2-7-5-3-4-6-8(7)12(9,10)11/h3-6H,2H2,1H3,(H2,9,10,11)
• Molekulargewicht: 185.250

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Benzene and substituted derivatives
      • Subclass Benzenesulfonamides

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Benzenesulfonamides
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzenesulfonamides
• Alternative Parents: Benzenesulfonyl compounds Organosulfonamides Aminosulfonyl compounds Organic oxides Organic nitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzenesulfonamide - Benzenesulfonyl group - Organosulfonic acid amide - Aminosulfonyl compound - Sulfonyl - Organosulfonic acid or derivatives - Organic sulfonic acid or derivatives - Organic nitrogen compound - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organosulfur compound - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
• 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: 185.250 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 185.051 Da
• Monoisotopic Mass: 185.051 Da
• Topological Polar Surface Area: 68.500 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 230.000
• 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 standardized bioassay or immunoassay protocols apply to this small-molecule building block. For synthetic use, see the Reaction Conditions and Synthetic Utility sections for practical procedures and optimization tips. For analytical handling, prepare stock solutions in DMSO (e.g., 10–100 mM), then dilute into compatible mobile phases (MeCN/H2O with 0.1% formic acid) for LC–MS, ensuring the final DMSO content avoids precipitation.

Biological Roles

• Item-specific claims: None. For research use only.

• General context (literature)

  • Sulfonamide functional groups are prevalent in bioactive molecules, acting as strong hydrogen bond donors/acceptors and conferring high polarity and metabolic stability due to the robust S(VI) center.
  • Aryl sulfonamides often mimic bioisosteres of carboxylic acids or amides in medicinal chemistry, modulating pKa and solubility to tune target engagement.
  • The ortho‑ethyl substituent increases lipophilicity and steric bulk near the NH, potentially influencing membrane permeability and binding pocket fit in structure–activity studies.

• Metabolism & stability (general)

  • Primary aryl sulfonamides typically resist hydrolysis under physiological conditions; metabolic transformations may include N‑acylation, N‑oxidation (rare), or aromatic hydroxylation on the ring depending on substituents.

• Experimental use

  • 2‑Ethylbenzene‑1‑sulfonamide can serve as a fragment or substructure for generating focused libraries to probe sulfonamide‑specific interactions (e.g., carbonic anhydrase, protease S1 pockets) in biochemical assays.

Note: No medical, diagnostic, or therapeutic use is claimed or intended. Any biological evaluation should be performed under appropriate institutional approvals.

Buffer Applications

This compound is a neutral/weakly acidic organic solid used as a synthetic building block, not a buffering agent. It is not commonly employed to prepare pH buffer systems. For solution work, select a conventional buffer (e.g., phosphate, HEPES, acetate) appropriate to your pH range, and dissolve the sulfonamide in a compatible co‑solvent if required (e.g., DMSO) before dilution into the buffered medium.

Green Alternatives

Although this product is a solid building block rather than a solvent or catalyst, greener choices can be made around its use.

• Greener solvent choices (literature guidance)

  • Replace DMF/DMAc/NMP with safer polar aprotics where feasible: propylene carbonate (PC), Cyrene (dihydrolevoglucosenone), or sulfolane for high‑temperature N‑functionalizations; MeCN or 2‑MeTHF for moderate‑polarity needs.
  • For recrystallization, prefer ethanol or isopropanol over chlorinated solvents.

• Bases and reagents

  • Use inorganic carbonates (K2CO3, Cs2CO3) over strong alkoxides or NaH when chemoselectivity allows, reducing hazards and workup complexity.
  • For acylations, consider acid anhydrides with catalytic DMAP instead of acyl chlorides to reduce HCl byproduct and corrosivity.

• Small comparison (typical)

  • DMF: excellent solubilizer; reproductive toxin concerns and difficult removal.
  • MeCN: lower toxicity profile, easy to remove; sometimes poorer solubility for highly polar sulfonamides.
  • 2‑MeTHF: bio‑derived, water‑immiscible; good for extractions and some crystallizations; limited polarity for difficult dissolutions.

• Process intensification

  • Employ microwave or flow conditions to shorten reaction times and reduce solvent volumes.
  • Explore solvent‑free (neat) N‑alkylations with phase‑transfer catalysis for suitable electrophiles, minimizing solvent use.

Tradeoffs should be balanced against yield, selectivity, and safety; validate any change on small scale.

Pharmaceutical Uses

• Item-specific status: For research use only; not for human or veterinary use.

• General formulation/manufacturing context (literature)

  • Aryl sulfonamides frequently appear as intermediates or structural motifs in drug discovery. 2‑Ethyl substitution can modulate physicochemical properties (e.g., lipophilicity, steric profile) of lead compounds.
  • As a raw material, this sulfonamide may be N‑functionalized to generate secondary sulfonamides or N‑acylsulfonamides used in medicinal chemistry campaigns.
  • Excipients: aryl sulfonamides are not standard excipients; use is typically as an API intermediate or reference material in analytical development.

• Regulatory considerations

  • No pharmacopeial monograph is known for this specific compound. Any GMP or regulatory use would require bespoke specification setting, impurity profiling, and method validation.

No therapeutic claims are made. Use is limited to laboratory R&D.

Physical Properties

• Item-specific specs

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general properties (non-spec, typical for aryl sulfonamides with small alkyl substituents)

  • Physical state: typically a crystalline solid.
  • Acid–base: primary aryl sulfonamides are weak acids; pKa (benzenesulfonamide) ~10–10.5 (literature). Ortho-alkyl substitution slightly modulates acidity but remains in this range.
  • Hydrogen bonding: one H‑bond donor (NH) and two strong acceptors (S=O), often leading to relatively high melting points and low volatility compared to hydrocarbons of similar MW.
  • Solubility tendencies: sparingly soluble in water; soluble in polar organic solvents (e.g., DMSO, DMF, NMP) and moderately soluble in alcohols and chlorinated solvents; limited solubility in nonpolar hydrocarbons. Actual solubility should be verified experimentally for critical processes.
  • Partitioning: aryl sulfonamides are amphiphilic; an ortho ethyl group increases hydrophobicity relative to benzenesulfonamide, increasing logP, while the sulfonamide maintains polarity (literature trend).
  • Thermal behavior: aryl sulfonamides are thermally robust solids; decomposition typically occurs well above their melting point; avoid sustained heating above melting without inert atmosphere to prevent discoloration.

Note: Where exact numeric values (mp, bp, density, refractive index) are needed for process or safety calculations, consult primary literature or request the CoA/Spec Sheet for this specific lot.

Quality and Grades

• Item-specific status

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/Additives: Not specified for this item; refer to CoA/Spec Sheet.

• Guidance on interpreting grades (general)

  • Research grade: suitable for most synthetic/analytical research. Purity typically reported by HPLC/GC/NMR; residual solvents and water reported on CoA.
  • High-purity or ≥98–99% grade (if specified on CoA): recommended for structure–activity studies and when impurity profiles may affect catalysis or assay outcomes.
  • Low-UV or HPLC grade (when applicable): indicates low background at analytical wavelengths; important if using as a reference standard.

• Sulfonamide-specific quality notes

  • Residual inorganic salts (from neutralization steps) and high-boiling polar organics (DMF/DMSO) are common trace impurities; drying under high vacuum at mild temperature can reduce volatiles.
  • Polymorphism is uncommon but crystal habit can vary with recrystallization solvent; if crystallinity matters (e.g., for solid-state studies), specify recrystallization conditions.

• Documentation

  • Request the CoA for lot-specific: assay method and result, identity confirmation (1H/13C NMR, IR with strong S=O bands ~1320–1150 cm⁻¹), residual solvent content, and water (Karl Fischer) if applicable.

Reaction and Applications

• Typical roles of 2‑ethylbenzenesulfonamide in synthesis (literature)

  • Versatile aryl sulfonamide scaffold used in medicinal chemistry libraries to probe H‑bonding and polarity; the ortho‑ethyl group tunes lipophilicity and steric environment around the NH.
  • N‑Functionalization: deprotonation (e.g., K2CO3, Cs2CO3, NaH) followed by alkylation (RX), acylation (acyl chlorides/anhydrides), or carbamoylation to access secondary sulfonamides, N‑acylsulfonamides, and ureas/carbamates.
  • Sulfonamide as directing/protecting element: the -SO2NH- strongly deactivates the ring (meta‑directing in EAS). Under metalation conditions (e.g., s‑BuLi/TMEDA), sulfonamides can participate in directed ortho metalation on suitably substituted rings; the existing ortho ethyl may bias regioselectivity in further functionalization.
  • Cross-coupling precursor elaboration: while aryl sulfonamides are not traditional coupling handles, N‑arylation (Buchwald–Hartwig) uses sulfonamides as nucleophiles to form N‑aryl sulfonamides with aryl halides or pseudohalides.

• Practical tips

  • Ensure anhydrous conditions for base‑promoted N‑alkylations; residual water suppresses deprotonation and favors hydrolysis of electrophiles.
  • For selective mono‑N‑alkylation, use mild base (K2CO3/Cs2CO3) and a slight excess of the sulfonamide; stronger bases (NaH) and excess electrophile can promote dialkylation.
  • Monitor reactions by LC–MS: sulfonamide derivatives ionize well in ESI (often [M+H]+), and characteristic IR bands (S=O at ~1320/1150 cm⁻¹) aid quick identification.
  • Purification: products often crystallize well; if oils persist, trituration with hexanes/Et2O can induce solidification.

Reaction Conditions

General, literature-based guidance for typical transformations involving 2‑ethylbenzenesulfonamide:

• N‑Alkylation

  • Conditions: K2CO3 or Cs2CO3 (2–3 equiv) in DMF, MeCN, or acetone; add alkyl halide (1.1–1.5 equiv).
  • Temperature/time: 25–60 °C for 4–24 h, depending on electrophile reactivity.
  • Tips: Use KI (10 mol%) as a Finkelstein promoter for alkyl chlorides; for sterically hindered electrophiles, switch to NaH (1.1–1.5 equiv) in THF/DMF at 0–25 °C.

• N‑Acylation (to N‑acylsulfonamides)

  • Conditions: acyl chloride (1.05–1.2 equiv), base (Et3N or pyridine, 1.5–2 equiv), solvent DCM or MeCN; catalytic DMAP (5–10 mol%) accelerates.
  • Temperature/time: 0 °C to rt, 1–3 h; quench with aqueous bicarbonate.

• N‑Arylation (Buchwald–Hartwig)

  • Conditions: aryl bromide/chloride (1.2 equiv), Pd catalyst (1–3 mol%), ligand (e.g., XPhos/BrettPhos), base (NaOtBu or Cs2CO3), solvent toluene or dioxane.
  • Temperature/time: 80–110 °C, 6–16 h.

• Directed metalation (where applicable)

  • Conditions: s‑BuLi or n‑BuLi with TMEDA in THF at −78 to −40 °C, followed by electrophile trapping.
  • Note: the existing ortho‑ethyl substituent constrains available positions; verify regioselectivity experimentally.

• Workup and purification

  • Aqueous quench followed by extraction (EtOAc). Crystallization from alcohols or EtOAc/hexanes is often effective. Residual polar solvents can be removed by high‑vacuum drying at 40–50 °C.

All conditions are general literature guidance; optimize on small scale for your substrates.

Safety and Handling

• Item-specific hazard classifications

  • Signal Word: Not specified for this item; refer to SDS.
  • H‑Statements: Not specified for this item; refer to SDS.
  • GHS Classification/Pictograms: Not specified for this item; refer to SDS.

• General safety considerations for aryl sulfonamides (literature/typical)

  • Likely hazards: may cause skin/eye irritation and respiratory tract irritation if dusts are generated. Low volatility reduces inhalation risk under normal handling; avoid dust formation.
  • PPE: lab coat, safety glasses or goggles, appropriate gloves (e.g., nitrile). Use a dust mask or respirator if airborne particulates may form; conduct weighing/transfers in a fume hood.
  • First aid overview: rinse eyes/skin with water for several minutes if contacted; remove contaminated clothing; if inhaled, move to fresh air; if swallowed, rinse mouth. Seek medical attention per SDS guidance.
  • Incompatibilities: strong oxidizers, strong bases (can deprotonate the sulfonamide), and strong dehydrating agents. Avoid reactive acylating or sulfonylating reagents unless intended.
  • Thermal stability: stable at ambient conditions; avoid excessive heating. Combustion may produce SOx and NOx.

• Handling & hygiene

  • Minimize dust; keep container tightly closed.
  • Use clean, dry tools; avoid moisture ingress that can cause caking.

Always consult the product’s SDS for authoritative, up‑to‑date hazard and response information. For research use only.

Solvent Selection

This product is a solid aryl sulfonamide building block rather than a process solvent. Solvent choice is relevant for dissolution, purification, and reactions on the sulfonamide nitrogen or aromatic ring.

• Polarity and solubility guidance (literature/typical)

  • Readily soluble: DMSO, DMF, NMP, DMAc; hot ethanol/methanol; acetone; acetonitrile (moderate).
  • Moderately soluble: ethyl acetate, dichloromethane, chloroform, isopropanol.
  • Sparingly soluble: water; nonpolar hydrocarbons (hexanes, toluene) unless heated.

• Use-case driven choices

  • N‑alkylation/N‑acylation: polar aprotic solvents (DMF, DMSO, MeCN) with base (K2CO3, Cs2CO3, NaH). These maximize deprotonation and nucleophilicity of the sulfonamide nitrogen.
  • Crystallization/purification: exploit low aqueous solubility for antisolvent crystallization from ethanol or ethyl acetate with water or heptane as antisolvent; adjust based on small-scale screening.
  • Analytical prep: dissolve in DMSO to make concentrated stocks; dilute with MeCN/H2O for LC analyses, watching for limited aqueous solubility.

• Quick comparison (literature trends)

  • DMF vs DMSO: both excellent for N‑functionalization; DMSO is easier to remove by aqueous workup but can over-oxidize sensitive partners.
  • MeCN: cleaner workups, lower boiling; may need higher temperatures for complete dissolution.
  • Alcohols: useful for recrystallization; less ideal for strong-base chemistry due to proton donation.

Storage and Reconstitution

• Item-specific storage

  • Storage Conditions: Room temperature (as provided).
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• General guidance for aryl sulfonamide solids

  • Keep tightly closed in a dry, well‑ventilated place. Protect from prolonged exposure to moisture to prevent caking and from strong light/heat.
  • If long‑term storage is anticipated, consider desiccation (P2O5 or silica gel) to maintain low water content.

• Reconstitution/solution preparation

  • Prepare concentrated stocks in DMSO, DMF, or MeCN depending on downstream use. Typical research stocks: 10–100 mM in DMSO.
  • For aqueous systems, first dissolve in a miscible organic co‑solvent (e.g., DMSO), then dilute into buffer with vigorous mixing; final organic content should be kept low to avoid precipitation (e.g., ≤1–5% v/v DMSO).
  • Filter solutions (0.2 µm PTFE) for analytical purposes.

• Stability of solutions (general)

  • DMSO/DMF solutions are usually stable for days at 2–8 °C; for longer storage, aliquot and freeze (−20 °C) to minimize freeze–thaw cycles. Discard if discoloration or precipitate forms.

For precise shelf life and solution stability, consult the lot-specific CoA or SDS.

Structure and Identity

Brief description: 2‑Ethylbenzene‑1‑sulfonamide is an aryl sulfonamide featuring a benzene ring bearing an ortho ethyl substituent and a para-orienting but overall deactivating sulfonamide group (-SO2NH2) at C1.

• Item-specific (from Product Data)

  • Product name: 2‑Ethylbenzene‑1‑sulfonamide
  • CAS: 85-92-7
  • CID: 15695366
  • InChIKey: 242093 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature identity details (general reference values)

  • Molecular formula (literature): C8H11NO2S (aryl sulfonamide with an ortho ethyl group)
  • Molecular weight (literature): ~185.25 g/mol
  • Canonical SMILES (typical representation): CCc1ccccc1S(=O)(=O)N (positional isomeric detail implied by name)
  • Key functional groups: primary sulfonamide (-SO2NH2), aryl ring, ethyl substituent
  • Structural features in words: A benzene ring where the sulfonamide group occupies position 1 and an ethyl group occupies position 2 (ortho), giving a hydrogen‑bond donor (NH) and two strong S=O acceptors; the sulfonyl moiety strongly deactivates the ring toward electrophilic substitution and is meta‑directing.

• Stereochemistry: None (achiral, no stereogenic centers).

Synthetic Utility

• Functional group behavior

  • Sulfonamide NH: weakly acidic, enabling selective deprotonation and subsequent N‑alkylation, N‑arylation (Buchwald–Hartwig), or N‑acylation to tailor polarity and H‑bonding.
  • Sulfonyl group: strong -I effect; overall deactivates the ring and directs electrophilic substitution meta. It stabilizes adjacent carbanions under strong base, enabling directed ortho metalation in some systems.

• Transformations enabled (literature)

  • Secondary sulfonamides: via alkyl halides/epoxides under carbonate or NaH base.
  • N‑Acylsulfonamides: via acyl chlorides/anhydrides; these are useful as amide bioisosteres and can serve as acyl transfer agents in synthesis.
  • Ureas/carbamates: via isocyanates or chloroformates to decorate the sulfonamide nitrogen.
  • Reductive manipulations: N‑alkylated sulfonamides can sometimes be deprotected (e.g., via strong reductants like Li/naphthalene or with thiol‑mediated protocols) when used as temporary protecting elements.

• Retrosynthetic value

  • The aryl sulfonamide core can serve as a convergent handle: late‑stage diversification at nitrogen without perturbing other ring substituents (the ortho ethyl remains intact), useful for parallel library synthesis.

• Practical notes

  • Choose base and solvent to balance reactivity and selectivity: carbonates for mono‑alkylation; NaH for challenging electrophiles.
  • TLC/IR monitoring is convenient: disappearance of NH stretch (~3300–3400 cm⁻¹) and changes in S=O region signify conversion.

Target Specificity

Not applicable. This product is a small-molecule sulfonamide building block, not a biological macromolecule or affinity reagent. No antigen, epitope, clone, isotype, or species reactivity information applies.