Hexyl isocyanide - ≥95% , CAS No.15586-23-9

CAS: 15586-23-9 Cat. No.: H1041083 Formula: C₇H₁₃N Peso molecolare: 111.180 Numero EC: 897-645-0

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

• Sorrisi canonici: CCCCCC[N+]#[C-]
• IUPAC Name: 1-isocyanohexane
• InChIKey: AWJCOFYWVBNFET-UHFFFAOYSA-N
• INCHI: 1S/C7H13N/c1-3-4-5-6-7-8-2/h3-7H2,1H3
• Peso molecolare: 111.180

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic nitrogen compounds
    • Classe Organonitrogen compounds
      • Subclass Organic isocyanides

• Kingdom: Organic compounds
• Superclass: Organic nitrogen compounds
• Classe: Organonitrogen compounds
• Subclass: Organic isocyanides
• Intermediate Tree Nodes: Not available
• Direct Parent: Organic isocyanides
• Alternative Parents: Organopnictogen compounds Hydrocarbon derivatives
• Molecular Framework: Aliphatic acyclic compounds
• Substituents: Organic isocyanide - Organopnictogen compound - Hydrocarbon derivative - Aliphatic acyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as organic isocyanides. These are organic compounds containing the isomer HN+#C- of hydrocyanic acid, HC#N, or its hydrocarbyl derivatives RNC (RN+#C-).
• 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

Proprietà chimiche e fisiche

• Peso molecolare: 111.180 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 4
• Exact Mass: 111.105 Da
• Monoisotopic Mass: 111.105 Da
• Topological Polar Surface Area: 4.400 Ų
• Heavy Atom Count: 8
• Formal Charge: 0
• Complexity: 77.600
• 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 assay or bioanalytical application protocols are specified for this item. As a synthetic reagent, usage is protocol-dependent on the chosen reaction (e.g., Ugi, Passerini, metal-catalyzed insertions). Refer to the Reaction Conditions and Reaction & Applications sections for practical starting points and adjust to your substrate set.

Biological Roles

Item-specific biological/biochemical roles: Not specified for this item; refer to CoA/Spec Sheet.

General context (literature):

• Hexyl isocyanide is a synthetic small molecule with no established physiological role. While isocyanide functional groups occur in certain marine and terrestrial natural products, simple aliphatic isocyanides like hexyl isocyanide are primarily laboratory reagents.
• In chemical biology and medicinal chemistry workflows, isocyanides are widely used to generate compound libraries via Ugi/Passerini MCRs for target screening. Any biological activity arises from the final products, not from the isocyanide reagent itself.
• Reactivity in aqueous/biological media is limited by hydrophobicity and the inherent reactivity of the isocyanide moiety; direct use in biological systems is uncommon outside of synthesis.

Note: For research use only. No medical, diagnostic, or therapeutic applications are implied for this reagent.

Buffer Applications

Not typically applicable. Hexyl isocyanide is a hydrophobic, reactive small-molecule reagent used in organic synthesis rather than as a buffering component. For experimental planning in aqueous systems, focus on the Reaction & Applications and Solvent Selection sections for suitable organic or mixed-solvent conditions.

Green Alternatives

Isocyanide chemistry carries unique EHS challenges (odor, acute toxicity, lifecycle impacts). Greener strategies focus on solvent choice, containment, and safer surrogates rather than eliminating the isocyanide when the reaction demands it.

Greener considerations (literature/general):

• Solvent optimization:
  • Prefer 2-MeTHF or CPME over THF/DCM where compatible (better safety metrics, biorenewable 2-MeTHF).
  • Ethyl acetate or alcohols (MeOH/EtOH) for Ugi/Passerini can reduce halogenated solvent waste.
• Process intensification:
  • Microflow or sealed-vial high-concentration MCRs lower solvent volume and confine odor.
  • Solid-supported acid catalysts (e.g., sulfonated resins) can facilitate workup in Passerini/Ugi variants.
• Safer isocyanide surrogates (context-dependent):
  • tert-Butyl isocyanide often perceived as more manageable odor-wise but is still hazardous.
  • In situ generation from formamides (e.g., using POCl3, triphosgene, or dehydration reagents) minimizes storage/handling of neat isocyanide; continuous flow variants further reduce exposure.
  • Odorless/low-odor specialized isocyanides (e.g., TosMIC) are alternatives in some transformations but are not drop-in replacements for all MCRs.

Trade-offs:

• Alternative solvents may alter chemoselectivity or rates; benchmark yields and E-factors.
• In situ generation introduces dehydrating reagents with their own hazards; evaluate total process risk.

Comparison snapshot (general):

• DCM vs EtOAc/2-MeTHF: Similar solubility for many MCR substrates; greener options reduce halogenated waste, sometimes at slight rate penalties.

Pharmaceutical Uses

Item-specific pharmacopeial status or excipient role: Not specified for this item; refer to CoA/Spec Sheet.

General, non-clinical context:

• Role in process R&D: Hexyl isocyanide is employed as a building block in multicomponent reactions to access peptidomimetic scaffolds, heterocycles, and diversity-oriented libraries during hit identification and SAR exploration.
• Formulation/excipient status: None. Isocyanides are reactive and odorous; they are not used as excipients.
• Regulatory considerations: Due to strong odor and potential acute toxicity, manufacturing-scale operations require enhanced containment, off-gas treatment (activated carbon scrubbers), and odor complaint mitigation plans. Residual isocyanide specifications in intermediates/final APIs are typically controlled to low ppm by validated purge steps.

This information pertains to manufacturing and research chemistry context only; no therapeutic claims are made.

Physical Properties

Item-specific specifications (exact values, cutoffs): Not specified for this item; refer to CoA/Spec Sheet.

Literature/general reference values for hexyl isocyanide (for planning purposes only):

• Physical state: Colorless to pale yellow, intensely odorous liquid (literature)
• Boiling point: ~158–160 °C at 1 atm (literature)
• Melting point: < −60 °C (literature, isocyanides of this chain length remain liquid at subzero temps)
• Density: ~0.82–0.84 g/mL at 20–25 °C (literature)
• Refractive index (nD20): ~1.420–1.425 (literature)
• Vapor pressure: Low–moderate for a C7 liquid; handle in fume hood due to strong odor (qualitative, literature)
• Solubility:
  • Water: Very low (estimated <1 g/L); may form surface films (literature)
  • Organic solvents: Miscible with most nonpolar and moderately polar solvents (hexanes, toluene, DCM, THF, MeCN, EtOAc); moderately soluble in alcohols (literature)
• Partitioning: logP estimated ~2.5–3.0 (literature; consistent with C6 aliphatic chain and isocyanide group)
• pKa: Isocyanides are very weak bases at nitrogen; no relevant aqueous pKa (literature)

Practical notes (general):

• Odor threshold is extremely low; even minute vapors are perceptible—ensure robust containment.
• Refractive index and density are commonly used for quick identity checks; confirm against CoA/SDS for acceptance ranges.

Quality and Grades

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

Guidance on grades for isocyanide reagents (general):

• Research/ACS grades for reactive building blocks typically control identity (GC/GC–MS, NMR), assay (% area by GC), and key impurities (parent amine, formamide precursors, higher-boiling residues). For isocyanides, residual amine or formamide can strongly affect multicomponent reactions (MCRs), so assay and impurity profile matter more than trace water.
• Low-UV or HPLC-grade specifications are not typical for isocyanide reagents unless explicitly required for photophysical applications. If chromatographic uses are intended, request UV-cutoff and trace-absorber data.
• Odor containment: Suppliers may use specialty caps and liners; maintain closure integrity to preserve quality and minimize odor permeation.

Recommendations:

• Review the CoA for: assay (%), identity (NMR/IR νNC ~2140–2120 cm⁻¹), GC purity profile, and water (Karl Fischer) only if moisture-sensitive reactions will be performed.
• For library synthesis (Ugi/Passerini), batch-to-batch reproducibility is critical—retain sample retains and verify with a quick IR check of the isocyanide stretch prior to large runs.

Reaction and Applications

Hexyl isocyanide is a versatile C1 synthon in multicomponent and insertion chemistries. Its primary utility lies in assembling diverse scaffolds rapidly.

Key application families (literature):

• Ugi four-component reaction (Ugi-4CR): Combines an amine, carbonyl (aldehyde/ketone), carboxylic acid, and isocyanide to form peptidomimetic α-acylamino amide adducts. Hexyl isocyanide contributes a lipophilic N-substituent, often enhancing membrane affinity of products.
• Passerini three-component reaction: Carbonyl + carboxylic acid + isocyanide → α-acyloxy amides. Hexyl isocyanide frequently improves organic phase partitioning and crystallization behavior.
• Metal-catalyzed isocyanide insertions: Pd, Ni, Cu, Au catalysis to form imidoyl metal intermediates leading to imidamides, imidoyl halides, or heterocycles (e.g., imidazo[1,2-a]pyridines, benzoxazoles) via isocyanide-based annulations.
• Radical and photoredox chemistry: Isocyanide carbon as radical acceptor enabling imidoyl radical formation; used in cascade cyclizations and Minisci-type variants.
• Ligand/coordination uses: Isocyanides bind metals via carbon (isoelectronic with CO), enabling organometallic studies; n-hexyl substituent tunes sterics/solubility.

Practical tips:

• Drying: Typically used as received; for water-sensitive catalysis, pass through basic alumina or dry over molecular sieves briefly, minimizing odor release.
• IR monitoring: Strong νNC at ~2140–2120 cm⁻¹; consumption indicates progression in MCRs.
• Equivalents: 1.0–1.5 equiv commonly used; excess may suppress side reactions but increases odor load—optimize stoichiometry.
• Quench/cleanup: Residual isocyanide odor can persist; oxidizing rinses (carefully applied) and activated carbon help decontaminate glassware.

Reaction Conditions

General literature guidance for common transformations using hexyl isocyanide:

• Ugi 4CR (amine + carbonyl + carboxylic acid + isocyanide):

  • Solvent: MeOH, EtOH, or MeCN; DCM/MeOH mixtures for poorly soluble substrates.
  • Stoichiometry: 1.0 equiv each component; 1.2–1.5 equiv isocyanide sometimes used to drive to completion.
  • Temperature/time: 20–50 °C, 2–24 h; microwave heating (60–90 °C) can reduce times to 10–60 min.
  • Additives: Mild acid catalysis (AcOH) can accelerate imine formation when using less reactive ketones.
  • Typical isolated yields: 50–90% depending on substrate set (literature ranges).

• Passerini 3CR (carbonyl + carboxylic acid + isocyanide):

  • Solvent: DCM, MeCN, EtOAc; sometimes catalytic TFA (0.1–0.5 equiv).
  • Temperature/time: 0–25 °C, 2–24 h; cooling can improve selectivity for sensitive aldehydes.
  • Yields: Commonly 40–85% (literature).

• Metal-catalyzed isocyanide insertion/annulation:

  • Catalysts: Pd(PPh3)4, Pd(OAc)2/ligand, CuI, Au catalysts, etc.
  • Solvent: Toluene, dioxane, DMF/MeCN; base or acid as required by the manifold.
  • Temperature: 60–130 °C; inert atmosphere often necessary.
  • Notes: Control isocyanide equivalents to avoid catalyst poisoning; slow addition may help.

• Photoredox/radical additions:

  • Photocatalyst: Ir/Ru complexes or organic dyes; blue LEDs.
  • Solvent: MeCN, DCM, or acetone; 20–35 °C; 2–12 h.

These are representative literature conditions offered for planning; optimize per substrate and consult primary references.

Safety and Handling

Item-specific hazard statements, pictograms, and GHS classification: Not specified for this item; refer to SDS.

General safety profile for aliphatic isocyanides (literature/industry practice):

• Hazards: Strongly odorous; may cause acute toxicity by inhalation/ingestion, skin and eye irritation, and respiratory irritation. Some isocyanides are classified as Acute Tox. and Skin/Eye Irrit. Consult the SDS for the definitive classification of this SKU.
• Engineering controls: Handle exclusively in a certified chemical fume hood. Use closed transfers where possible; double-contain waste.
• PPE: Lab coat, nitrile gloves (change frequently), splash goggles. For bulk handling or high vapor conditions, consider organic vapor respirator per institutional policy.
• First aid (overview—defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eyes: Immediately flush with water for ≥15 min; remove contaminated clothing.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.
• Incompatibilities and reactivity (general): Strong oxidizers; strong acids can promote side reactions (e.g., formimidate formation in multicomponent chemistry). Avoid prolonged exposure to light/air that may lead to slow degradation/odor intensification.
• Special risks: Powerful, pervasive odor; trace contamination can impact shared lab spaces—clean tools/glassware promptly, segregate waste, and use odor-absorbing media (activated carbon) in vents.
• Spill response: Absorb with inert material (vermiculite/activated carbon), seal waste promptly, ventilate area thoroughly. Decontaminate with oxidizing bleach solutions only if compatible with local EHS guidance.

Always consult the product’s SDS for authoritative safety, toxicological, and regulatory information.

Solvent Selection

Hexyl isocyanide is used as a reagent, not a reaction solvent. Choosing the medium impacts MCR rates and selectivity.

• Polarity/miscibility (literature, general):

  • Nonpolar to moderately polar aprotic media dissolve it well: DCM, CHCl3, EtOAc, toluene, THF, CPME, 2-MeTHF, MeCN.
  • Protic solvents (MeOH, EtOH, i-PrOH) can be used in Ugi reactions and often accelerate imine formation but may influence byproduct profiles.
  • Water or aqueous mixtures: Limited solubility; nevertheless, micellar or water–ethanol systems have been reported for Ugi/Passerini variants.

• Practical selection by application:

  • Ugi 4CR: MeOH, EtOH, or MeCN are commonly optimal; DCM for less polar substrates. Mixed MeOH/DCM often balances solubility and rate.
  • Passerini 3CR: DCM, MeCN, or EtOAc; catalytic acid sometimes added, choose solvent that tolerates it.
  • Metal-catalyzed isocyanide insertions: Toluene, dioxane, or DMF/DMSO depending on catalyst system; rigorously exclude air/moisture when required by the catalyst.

• Odor management: Prefer closed-vial microreactors or crimp-sealed vials; minimize headspace and use septa-compatible solvents (MeCN, DCM, toluene) for syringe transfers.

Comparison note:

• tert-Butyl isocyanide is more volatile but can be less offensive odor-wise; hexyl isocyanide offers better lipophilicity and lower volatility, often beneficial for handling and product extraction.

Storage and Reconstitution

• Storage conditions (item-specific): Room temperature (per Product Data). Store tightly closed in the original container.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable; supplied as a neat liquid reagent.

Best practices (general for isocyanides):

• Containment: Keep bottles well-sealed with PTFE-lined caps; consider secondary containment to prevent odor permeation.
• Atmosphere: While many aliphatic isocyanides are air-stable, storing under inert gas (N2/Ar) and protecting from light can help minimize slow degradation and odor intensification over time.
• Moisture: Not highly moisture sensitive, but dry storage (desiccator or low-humidity cabinet) preserves assay and simplifies use in moisture-sensitive catalysis.
• Temperature: Ambient is acceptable; avoid excessive heat. Refrigeration is generally unnecessary and may not mitigate odor.
• Handling: Open only in a fume hood. Use septum and syringe/positive-displacement pipette to limit vapor release.
• Shelf life: Verify integrity periodically by IR (νNC ~2140–2120 cm⁻¹) and GC; any significant reduction of νNC or off-spec GC profile indicates degradation.
• Waste: Cap waste promptly; segregate and vent via activated carbon where required by EHS.

For definitive storage and handling requirements, consult the product’s CoA and SDS.

Structure and Identity

Hexyl isocyanide (hexyl isonitrile) is a linear aliphatic isocyanide bearing a primary n-hexyl group bound to the isocyanide carbon (R–N≡C).

• Item-specific identifiers from Product Data:

  • CAS: 15586-23-9
  • InChIKey: 16656 (as provided; truncated/not standard)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identifiers and descriptors (for reference):

  • Common name: n-Hexyl isocyanide; hexyl isonitrile
  • Molecular formula: C7H13N (literature)
  • Molecular weight: 111.19 g/mol (literature)
  • Typical SMILES (literature): CCCCCCN#C
  • Functional groups: isocyanide (isonitrile, –N≡C), primary alkyl chain (n-hexyl)

• Structural features (2D description):

  • A straight-chain C6 alkyl fragment (–CH3–(CH2)5–) attached to an isocyanide carbon via the nitrogen atom (R–N≡C). The isocyanide moiety is linear (sp-hybridized carbon) with a formal C≡N bond order, presenting an ambident functionality (nucleophilic carbon, weakly basic nitrogen).
  • No stereocenters; acyclic, non-aromatic.

Notes:

• Where a precise, product-specific identifier is required (e.g., canonical SMILES, exact InChIKey), consult the item’s CoA/Spec Sheet. The literature values above are provided for general chemical context and do not supersede product documentation.

Synthetic Utility

Functional group behavior (literature):

• Ambident reactivity: The isocyanide carbon is nucleophilic and participates in additions to electrophiles (e.g., iminium ions in Ugi) forming nitrilium/imidoyl intermediates, which then capture nucleophiles.
• Multicomponent reactions: Cornerstone role in Ugi (4CR), Ugi–Smiles variants, Passerini (3CR), and post-condensation diversifications (cyclizations to diketopiperazines, lactams, and heteroaromatics).
• Isocyanide insertions: Transition-metal-mediated C–C/N–C bond formations via imidoyl-metal species, enabling acylation surrogates and heterocycle synthesis (e.g., imidazo[1,2-a]pyridines from 2-aminopyridines + aryl halides + isocyanide).
• Radical pathways: Visible-light or peroxide initiation to forge C–C bonds through imidoyl radicals, enabling remote functionalizations and cascade cyclizations.

Advantages of the hexyl substituent:

• Lipophilicity enhances solubility of adducts in organic media and can improve crystallization/phase separations.
• Lower volatility than C1–C4 isocyanides aids odor management and dosing accuracy.

Practical guidance:

• Select the isocyanide substituent (R) to tune product properties; hexyl provides hydrophobic N-substitution and can modulate permeability and PK proxies in discovery settings.
• IR handle: νNC at ~2140–2120 cm⁻¹ is a convenient diagnostic; disappearance correlates with complete consumption in MCRs.

Target Specificity

Not applicable—this product is a small-molecule reagent, not a biological macromolecule or antibody. No target, epitope, or species reactivity information applies.