isoamylisocyanide - Reagent grade

Cat. No.: I483399

GRADE & PURITY Reagent Grade

Storage

Room temperature

Specifications

Specifiche e purezza

Reagent grade

Condizioni di conservazione di stoccaggio

Room temperature

Grado

Reagent Grade

Application Protocols

Not applicable. This product is a chemical reagent and does not have WB/IHC/IF/FC-style biological application protocols. For practical usage, refer to Reaction & Applications and Reaction Conditions for literature-based synthetic procedures.

Biological Roles

This product is intended for research and laboratory use only. No medical or clinical uses are implied.

General/literature context:

• Aliphatic isocyanides are not endogenous metabolites and have no established physiological role in living systems.
• In chemical biology and biochemistry method development, isocyanide functionality has been explored as a ligand for transition metals (e.g., Fe, Pd, Au complexes) and as a component in bioorthogonal multicomponent ligations under mild conditions; however, the specific biological compatibility strongly depends on substrates, catalysts, and formulation.
• The –N≡C group can coordinate to heme and other metal centers (analogous in some respects to CO binding in a coordination sense), but such interactions are typically studied in vitro due to toxicity and reactivity concerns.

Practical note: If incorporating isocyanide-based ligations in biomolecular settings, carefully validate cytocompatibility and conduct thorough quenching/purification, as residual isocyanide is generally not biocompatible. Always consult institutional safety guidance for handling odorous/toxic reagents in biological laboratories.

Buffer Applications

Not typically applicable. Isoamyl isocyanide is a reactive organic building block, not a buffering agent. It is not used to prepare aqueous buffer systems. For experimental planning, refer instead to the Reaction & Applications, Synthetic Utility, and Reaction Conditions sections for relevant usage guidance.

Green Alternatives

Context: Isoamyl isocyanide is a reactive building block rather than a process solvent. Greener choices usually concern (1) the reaction medium and (2) selection of the isocyanide substituent for safer handling.

• Greener media (literature comparisons):

  • 2-MeTHF vs DCM: 2-MeTHF (bio-based, higher boiling, lower toxicity) often replaces DCM in Ugi/Passerini reactions with comparable yields and improved safety/ESG profile.
  • MeOH/EtOH vs DMF/DCE: lower-toxicity alcohols or MeCN can substitute for DMF or chlorinated solvents in many IMCRs, reducing environmental impact and improving workup.
  • Aqueous/solvent-minimized protocols: water-rich or solvent-free Ugi/Passerini procedures have been reported for certain substrate sets; feasibility depends on substrate solubility and stability (literature).

• Safer isocyanide choices (handling perspective):

  • Bulkier isocyanides (e.g., cyclohexyl isocyanide) can have somewhat reduced volatility/odor impact compared to lower-carbon analogs, aiding EHS without compromising reactivity (tradeoff: different steric profile can affect rates/selectivity).
  • Polymer-supported isocyanides enable easier separation and odor containment (tradeoff: reduced atom economy; may alter kinetics).

• Operational green tips:

  • Run closed-vessel reactions with efficient stirring to limit VOC emissions.
  • Recycle solvent where feasible and use in-line carbon scrubbers for vented vapors.
  • Minimize acid additives and moisture to avoid hydrolytic waste (formamides) and reprocessing.

Summary: Prioritize greener solvents (MeOH, EtOH, MeCN, 2-MeTHF) and containment practices. Selection of isoamyl isocyanide balances reactivity with reduced volatility vs smaller isocyanides, aiding odor/EHS management.

Pharmaceutical Uses

No therapeutic claims are made. This material is for research use only.

Formulation/manufacturing context (general, literature-based):

• Isoamyl isocyanide is not used as an excipient. Its primary role in pharmaceutical R&D is as a synthetic intermediate in discovery and library synthesis via multicomponent reactions (Ugi/Passerini) to access diverse scaffolds for SAR exploration.
• Pharmacopeia/compendial status: Not specified for this item; refer to CoA/Spec Sheet. Aliphatic isocyanides generally do not have compendial monographs as excipients due to odor/toxicity considerations.
• Process considerations: When used upstream in API route scouting, strict containment and efficient odor scrubbing are required. Workups typically include aqueous acid or base washes, followed by adsorbents (e.g., activated carbon) to remove trace malodorants.

Operational guidance: Design synthetic routes to consume isocyanide fully, with validated purge factors. Implement headspace/VOC controls, and document residuals by sensitive GC methods before advancing intermediates.

Physical Properties

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

Literature/general properties for isoamyl (isopentyl) isocyanide (for reference only; not product specifications):

• Physical state/appearance (literature): typically a colorless to pale yellow, highly odorous liquid.
• Odor: characteristic, extremely strong isocyanide odor; detectable at very low levels (nuisance/penetrating).
• Approximate molecular weight: ~97.16 g/mol (from C6H11N, literature).
• Density: aliphatic isocyanides in this carbon range commonly have densities lower than water (literature; check CoA/SDS for exact value).
• Boiling point: aliphatic C5 isocyanides typically distill in the mid- to high-140s °C range at ambient pressure (literature range; verify with primary data before process design).
• Melting point: generally well below 0 °C (literature trend for C5 aliphatic isocyanides).
• Refractive index: typically in the 1.40–1.45 range for aliphatic isocyanides (literature trend).
• Solubility: low in water; miscible with many common organic solvents (Et2O, hexanes, toluene, DCM, THF, MeCN, alcohols) (literature).
• Partitioning: nonpolar to weakly polar aprotic character; expected logP > 1 (literature expectation).

Notes for practitioners:

• Isocyanides can slowly hydrolyze (especially under acidic, moist conditions) to the corresponding formamides; maintain dry conditions to preserve purity.
• Because isocyanides are odoriferous, even trace contamination can be noticeable—use dedicated glassware where odor cross-contamination is a concern.

Quality and Grades

• Item-specific grade: Reagent Grade (as provided in Product Data).

What Reagent Grade generally signifies (general guidance):

• Intended for general laboratory synthesis where high chemical purity is required, but without additional guarantees tailored to chromatographic optics (e.g., HPLC UV cutoffs) or trace-metal limits typical of semiconductor/trace-metal grades.
• Reagent Grade typically supports most organic synthesis workflows, including multicomponent reactions (e.g., Ugi/Passerini) and metal-catalyzed transformations where routine scavenging/purification is anticipated.

Considerations specific to isocyanides:

• Odor management: even with high purity, trace impurities (e.g., formamides from hydrolysis) can markedly affect odor and reactivity. Verify identity and purity quickly by IR (strong νNC near ~2140–2160 cm−1, literature) and GC before scale-up.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. If unstabilized, maintain dryness and minimize acid exposure to limit hydrolysis.
• UV/Chromatographic performance: Not specified for this item; refer to CoA/Spec Sheet. If using for photochemical or analytical applications, confirm background absorbance on the batch CoA.
• Metals/residuals: Not specified for this item; refer to CoA/Spec Sheet. For sensitive catalysis, consider prewashing over basic alumina or performing a short-path distillation under inert atmosphere.

Documentation: Always consult the batch-specific CoA/SDS for assay, impurity profile, and any stabilizer content prior to critical applications.

Reaction and Applications

Isoamyl isocyanide is a versatile C1/N1 synthon used broadly in isocyanide-based multicomponent reactions (IMCRs) and related transformations (literature). Key application families and practical notes:

• Ugi four-component reaction (U-4CR): combines amine + carbonyl (aldehyde/ketone) + carboxylic acid + isocyanide to give α-acylamino amides. Isoamyl isocyanide is frequently chosen for its balance of reactivity and manageable handling compared to lower-boiling isocyanides. Tips: premix imine (or use slight acid catalysis), use 1.0–1.2 equiv isocyanide, run at rt to 50 °C in MeOH, MeCN, or 2-MeTHF; exclude strong acid after conversion to limit post-reaction hydrolysis.

• Passerini reaction: carbonyl + carboxylic acid + isocyanide to furnish α-acyloxy amides. Polar solvents (MeCN, CH2Cl2, MeOH) at 0 °C to rt are common; isoamyl isocyanide provides robust conversions with reduced volatility vs smaller isocyanides.

• Tetrazole synthesis: [3+2] cycloaddition of organic azides with isocyanides (often in the presence of Lewis/Brønsted acids) affording 1,5-disubstituted tetrazoles. Solvents: MeCN, toluene, or 2-MeTHF; temperatures 25–100 °C depending on substrates.

• Metal complexation and insertions: isocyanides are strong σ-donor ligands forming imidoyl-metal species; useful in catalytic and organometallic method development.

• Post-IMCR diversification: Ugi/Passerini adducts enable rapid library synthesis, with downstream cyclizations (e.g., Ugi-to-lactams, diketopiperazines) and late-stage functionalization.

• Functional group tolerance: isocyanide participates as a nucleophilic C-center; avoid strongly acidic conditions that quench reactivity or trigger hydrolysis to formamides.

Always verify batch purity (IR νNC ~2140–2160 cm−1, literature) and dryness before multicomponent assembly to ensure high conversions and minimize byproducts.

Reaction Conditions

General literature guidance (not product specifications):

• Ugi 4CR:

  • Typical stoichiometry: 1.0 equiv amine, 1.0 equiv aldehyde/ketone, 1.0 equiv carboxylic acid, 1.0–1.2 equiv isoamyl isocyanide.
  • Solvents: MeOH, EtOH, MeCN, 2-MeTHF, DCM.
  • Temperature/time: rt to 50 °C; 2–24 h depending on substrates.
  • Catalysis: a few mol% acid (e.g., AcOH) can accelerate imine formation; avoid strong mineral acids that promote isocyanide hydrolysis.
  • Isolated yields: commonly 60–90% across diverse substrates (literature ranges).

• Passerini 3CR:

  • Solvents: DCM, MeCN, MeOH; can run under solvent-minimized conditions with liquid substrates.
  • Temperature: 0 °C to rt; 2–24 h.
  • Notes: lower temperatures can improve selectivity for hindered systems.

• Tetrazole formation (azide + isocyanide):

  • Solvent: MeCN, toluene, or 2-MeTHF; optional Lewis/Brønsted acid.
  • Temperature: 25–100 °C (substrate-dependent); 4–16 h.

• Organometallic/ligand uses:

  • Inert atmosphere (N2/Ar), dry solvent (THF, toluene, MeCN).
  • Temperature: −78 °C to reflux depending on transformation; monitor by IR (νNC) or GC.

Process tips:

• Control odor by sealed reactors and cold traps/charcoal scrubbers.
• Verify completion by disappearance of ν(N≡C) in IR and/or GC; quench carefully to avoid exotherms and malodor release.
• Purification: flash chromatography on silica/alumina; residual odor can be reduced by brief treatment with activated carbon (test to avoid product loss).

Safety and Handling

Item-specific hazard classification: Not specified for this item; refer to SDS for authoritative information.

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

• GHS expectations: many aliphatic isocyanides are classified as flammable liquids, acutely toxic (oral/dermal/inhalation), skin/eye irritants, and specific target organ toxicity (single exposure) due to strong odor and irritancy. Always consult the SDS for the exact classification and pictograms for this SKU.
• Key hazards: highly penetrating odor; vapors can cause headache, nausea, and mucous membrane irritation. Liquid is irritating to skin and eyes. May be harmful if swallowed or inhaled. Flammable.
• PPE: use in a certified chemical fume hood. Wear lab coat, safety goggles (EN166/ANSI Z87.1), and chemical-resistant gloves (e.g., butyl rubber or laminated film; check permeation data). Consider double-gloving and rapid glove changes due to odor.
• Engineering controls: strong local exhaust; keep containers tightly closed. Use odor containment practices (parafilm over septa, secondary containment).
• Incompatibilities: strong acids (accelerate hydrolysis to formamides with heat release), oxidizers, nitrosating agents. Avoid prolonged contact with moisture.
• First aid (summary; defer to SDS):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: rinse with water for 15 minutes; remove contaminated clothing; obtain medical advice.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Fire: use CO2, dry chemical, or foam. Cool containers with water spray. Vapors may form explosive mixtures with air.
• Spill response: evacuate area, increase ventilation, absorb with inert material, seal waste in odor-tight container; prevent environmental release.

Solvent Selection

As a reagent (liquid) rather than a solvent, isoamyl isocyanide is typically dissolved in an organic medium for reactions.

• Polarity/miscibility (literature):

  • Character: weakly polar aprotic; predominantly hydrophobic.
  • Water: low solubility; immiscible to sparingly soluble.
  • Organic solvents: miscible with common media (DCM, toluene, Et2O, THF, MeCN, alcohols). MeOH/EtOH are common in Ugi/Passerini chemistry.

• Choosing the medium (use-case driven):

  • Multicomponent reactions (Ugi/Passerini): MeOH, EtOH, MeCN, or 2-MeTHF often provide good solubility and manageable odor; DCM or toluene used when substrates are lipophilic.
  • Metal-mediated insertions/ligations: toluene, THF, or MeCN frequently used; ensure low water content to suppress hydrolysis.
  • Tetrazole formations (azide + isocyanide): polar aprotic solvents (MeCN, DMF) frequently employed; consider greener options like MeCN or 2-MeTHF over DMF when possible.

• Practical tips:

  • Dry solvents (3 Å MS or distillation) help minimize formamide formation.
  • For odor control, run in closed systems with septa; consider solvent choices with lower volatility if headspace odor is problematic.

Small comparison (literature trends):

• MeOH: accelerates imine formation in Ugi; easy workup; greener; but can transesterify sensitive substrates.
• MeCN: broadly compatible; moderate polarity; good for azide couplings.
• 2-MeTHF: bio-based, water-tolerant; balances polarity and greener profile; good for scale-up with better odor containment than DCM.
• Toluene: good for nonpolar substrates; higher bp aids temperature control; less green.

Storage and Reconstitution

• Storage conditions (item-specific): Room temperature (per Product Data). Store tightly sealed in the original container.
• Additional best practices (general for isocyanides):
  • Keep in a cool, well-ventilated area, away from strong acids, oxidizers, and moisture.
  • Use PTFE-lined caps/septa and consider secondary containment to manage odor.
  • For long-term storage, an inert gas blanket (N2/Ar) and desiccation help maintain assay by limiting hydrolysis to formamides.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable; supplied as a neat liquid reagent. If a solution is needed, prepare fresh in a dry, compatible solvent (e.g., MeOH, MeCN, 2-MeTHF, toluene) immediately before use.
• Freeze–thaw guidance: Not applicable to neat liquid; avoid freezing/condensation cycles that could introduce moisture upon thawing.
• Shelf-life/assay checks: Not specified for this item; refer to CoA/Spec Sheet. Periodically verify by IR (νNC band), GC, and/or 1H/13C NMR to confirm integrity before critical use.

Research Use Note: For research use only.

Structure and Identity

Brief overview: Isoamyl isocyanide (also known as isopentyl isocyanide; 3-methylbutyl isocyanide) is a primary aliphatic isocyanide featuring a branched C5 alkyl chain bound to the isocyano functionality (–N≡C).

• Item-specific identifiers (this product):

  • CAS: Not specified for this item; refer to CoA/Spec Sheet.
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: 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/computed identity (for reference only):

  • Preferred name: Isoamyl (isopentyl, 3-methylbutyl) isocyanide
  • Molecular formula (literature): C6H11N
  • Exact mass (calculated from formula): ~97.089 Da (literature)
  • Average molecular weight (literature): ~97.16 g/mol
  • Representative SMILES (literature): CC(C)CCN#C
  • Functional groups: primary aliphatic isocyanide (isonitrile), branched alkyl chain (isoamyl)
  • Structural features (2D description): a 3-methylbutyl chain (CH3–CH(CH3)–CH2–CH2–) connected via a single bond to the isocyano nitrogen, which is linearly triple-bonded to a terminal carbon (–N≡C). The –N≡C unit is formally cumulene-like and linear; the carbon side chain is tetrahedral/branched at C2.

• Stereochemistry: None (achiral in its simplest constitution).

Synthetic Utility

Functional reactivity (literature):

• Nucleophilic carbon at isocyanide carbon: participates in multicomponent condensations (Ugi, Passerini), delivering amide or ester–amide frameworks with broad functional group tolerance.
• Ligand behavior: strong σ-donor ligand to transition metals; forms imidoyl-metal intermediates enabling migratory insertions and cross-coupling variants.
• Diversification: IMCR adducts can undergo intramolecular cyclizations (lactams, imidazolines, diketopiperazines), oxidations/reductions, and heterocycle formations (e.g., tetrazoles from azides + isocyanide; imidates/formamidines under appropriate conditions).

Named reactions and roles:

• Ugi 4CR and Ugi-Smiles variants (phenolic nucleophiles).
• Passerini 3CR (acid + carbonyl + isocyanide → α-acyloxy amides) and Passerini–Smiles.
• Groebke–Blackburn–Bienaymé (GBB) condensation for imidazo[1,2-a]pyridines/pyrimidines (with aldehydes and 2-aminopyridines-like substrates).
• Tetrazole formation via [3+2] cycloaddition with azides (often acid- or Lewis acid-catalyzed).

Practical tips:

• The sterics of the isoamyl group can influence Ugi/Passerini rates and downstream cyclizations; screening of isocyanide substituents can fine-tune outcomes.
• Maintain anhydrous, neutral-to-slightly acidic conditions during reaction; strong acids post-reaction can induce hydrolysis to formamides.
• For metal-mediated steps, rigorously exclude air/moisture; isocyanide ligands can be sensitive to oxidative conditions.

Analytics:

• IR: strong ν(N≡C) band ~2140–2160 cm−1 (literature).
• 13C NMR: isocyano carbon typically very downfield (ca. 150–165 ppm, literature), aiding identity confirmation.

Target Specificity

Not applicable. This product is a small-molecule reagent, not a biological targeting agent or antibody. No antigen/epitope specificity, clone, isotype, or species reactivity applies.