N-Butylformamide - ≥95% , CAS No.871-71-6

CAS: 871-71-6 Cat. No.: N1068065 Formula: C₅H₁₁NO Peso molecolare: 101.150

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

CCCCNC=O

IUPAC Name

N-butylformamide

InChIKey

QQGNLKJAIVSNCO-UHFFFAOYSA-N

INCHI

1S/C5H11NO/c1-2-3-4-6-5-7/h5H,2-4H2,1H3,(H,6,7)

Peso molecolare

101.150

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Classe Carboxylic acids and derivatives
      • Subclass Carboxylic acid derivatives
        • Level5 Carboxylic acid amides
          • Level6 Secondary carboxylic acid amides

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Classe: Carboxylic acids and derivatives
• Subclass: Carboxylic acid derivatives
• Intermediate Tree Nodes: Carboxylic acid amides
• Direct Parent: Secondary carboxylic acid amides
• Alternative Parents: Organopnictogen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aliphatic acyclic compounds
• Substituents: Secondary carboxylic acid amide - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Carbonyl group - Aliphatic acyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as secondary carboxylic acid amides. These are compounds containing a secondary carboxylic acid amide functional group, with the general structure RC(=O)N(R')H (R,R'=alkyl, aryl).
• External Descriptors: a small molecule

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: 101.150 g/mol
• XLogP3: 0.800
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 3
• Exact Mass: 101.084 Da
• Monoisotopic Mass: 101.084 Da
• Topological Polar Surface Area: 29.100 Ų
• Heavy Atom Count: 7
• Formal Charge: 0
• Complexity: 45.300
• 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

• Not applicable.
  • No immunoassay or bioassay application protocols (WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic or process uses, refer to the Reaction Conditions and Synthetic Utility sections for guidance.

Biological Roles

• Item-specific (Product Data)
  • Category path includes “生命科学” (life sciences), but no biological function is specified. Research use only.
• General/biochemical context (literature)
  • N-Butylformamide is a small synthetic amide and is not known as an endogenous metabolite or biochemical cofactor.
  • Physicochemical properties (amide H-bonding, moderate polarity) make it a useful proxy solvent/additive in method development for protein/peptide solubility studies, but it is not a buffer or biological reagent per se.
  • Amides can interact with proteins via hydrogen bonding and hydrophobic contacts; any such use should be empirical and system-specific.
• Compliance note
  • No clinical/therapeutic claims are made. Any life-science use should be strictly in vitro or ex vivo research settings with appropriate controls and biosafety measures.

Buffer Applications

• Not typically applicable.
  • N-Butylformamide is not a buffering agent and does not define a useful acid/conjugate-base pair for pH control in aqueous systems.
  • For aqueous method development requiring amide-like cosolvents, it may be used as an organic modifier, but standard biological buffers (e.g., phosphate, Tris, HEPES, MOPS) should provide pH control.

Green Alternatives

• Context
  • When N-butylformamide is used as a solvent, greener choices may be preferred depending on the reaction. As a reagent/precursor (e.g., for isocyanides), substitution is typically not feasible, but process intensification and safer dehydrating agents can reduce hazard.
• Potential alternatives (literature/general)
  • For polar aprotic solvent roles: Cyrene (dihydrolevoglucosenone), γ-valerolactone (GVL), propylene carbonate, dimethyl isosorbide (DMI), and sulfolane or 2-MeTHF (if lower polarity acceptable) are candidates.
  • For DMF/NMP replacement: Cyrene and GVL often mimic polarity with improved environmental profiles.
• Comparison highlights (general; qualitative)
  • N-Butylformamide: High bp, good polarity, H-bond donor/acceptor; amide-class regulatory scrutiny may apply in certain sectors.
  • Cyrene/GVL: Bio-based, lower toxicity profiles reported; viscosity and acidity profiles differ; may not tolerate very strong bases as well as amides.
  • Propylene carbonate: Green, high bp; limited basicity and different solvating ability; not H-bond donor.
• Practical guidance
  • Map the solvent’s role (polarity, donor number, H-bonding) and pilot a small DoE comparing rate/selectivity against greener candidates.
  • For isocyanide synthesis from formamides, greener dehydration protocols (e.g., catalytic dehydration, phosphorylating agents in continuous flow) can reduce reagent mass and exposure, though classic POCl3 methods remain common.

Pharmaceutical Uses

• Item-specific (Product Data)
  • No pharmacopeial grade or excipient status is specified for this item.
• General information (non-clinical; literature)
  • N-Butylformamide is not commonly used as a pharmaceutical excipient. Amide solvents (e.g., DMF, NMP) appear in drug substance manufacturing as process solvents or reagents, not typically in final dosage forms.
  • Potential roles in process chemistry: reagent for generating isocyanides (for combinatorial libraries) or as a high-boiling polar solvent in API intermediate steps.
• Compliance
  • For GMP or regulatory filings, solvent selection should follow ICH Q3C (residual solvents) and risk assessments. If used in synthesis, ensure appropriate purge to meet residual solvent limits; establish validated analytical methods (e.g., headspace GC) to quantify residuals.
  • No therapeutic or clinical claims are made for this product; it is for research and laboratory use only.

Physical Properties

• Item-specific (Product Data)
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight (Product Data): Not specified for this item; refer to CoA/Spec Sheet.
• Literature/Reference values (not item specifications)
  • Molecular weight (literature): 101.15 g/mol (for C5H11NO)
  • Physical state/appearance (literature): Typically a colorless to pale liquid with amide odor.
  • Boiling point (literature): ~200–210 °C at 101 kPa (reports commonly cite ~206 °C).
  • Melting point (literature): Well below 0 °C (reported negatives; e.g., < −40 °C).
  • Density (literature): ~0.90–0.93 g/mL at 20–25 °C.
  • Refractive index (literature): nD 20 ≈ 1.43–1.45.
  • Solubility (literature): Miscible with many polar organics (alcohols, ketones, chlorinateds); substantially soluble in water due to amide functionality.
  • Vapor pressure (literature): Low at ambient temperature (consistent with high bp amides).
  • pKa/basicity (literature): Amide N largely nonbasic (conjugate acid pKa typically < 1); strong H-bond donor/acceptor.
  • Partitioning (literature): Moderately polar; logP expected near zero to modestly positive for N-alkyl formamides.
• Notes
  • Values above are typical literature ranges for N-butylformamide and are provided for method planning only; do not treat as specifications for this catalog item.

Quality and Grades

• Item-specific (Product Data)
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/Additives: Not specified for this item; refer to CoA/Spec Sheet.
• Interpreting typical grades (general guidance)
  • Technical grade: Suitable for routine synthesis where trace impurities are tolerable. May have higher water/UV-absorbing impurities.
  • Reagent/ACS grade: Suitable for most laboratory syntheses; typical control of common impurities.
  • Anhydrous/low-water variants: Beneficial for moisture-sensitive reactions (e.g., dehydration to isocyanides, metal-catalyzed couplings). If water content matters, verify via Karl Fischer.
  • HPLC/UV-cut grades: Lower background absorbance; useful if employing as a sample matrix or solvent in analytical workflows.
• What to verify on receipt
  • Actual assay (GC), water content (KF), color/APHA, and any inhibitor content if applicable. For amide solvents/reagents, residual amines or formic acid are the common impurities.
• Documentation
  • For method qualification or GMP-adjacent work, request the current CoA and Spec Sheet for this SKU to confirm lot-specific assay, water, acidity/alkalinity, and trace metals (if relevant to your application).

Reaction and Applications

• Core uses (literature/general)
  • Precursor to isocyanides: Dehydration of N-alkylformamides to the corresponding isocyanides (isonitriles) using POCl3, PCl5, or SOCl2 with base is a standard route to n-butyl isocyanide—valuable for Ugi and other multicomponent reactions.
  • Reductions: Hydride reductions (e.g., LiAlH4) of N-alkylformamides provide N-methylated amines (here, N-methylbutylamine) via reduction of the formyl carbonyl.
  • Hydrolysis: Acidic or basic hydrolysis yields n-butylamine and formic acid/formate; useful in protecting-group strategies or amide cleavage studies.
  • Transamidation/formyl transfer: Under catalytic conditions (e.g., Ti, Zr, or boron catalysts), can participate in amide exchange or serve as a formyl source.
• Application notes
  • Isocyanide synthesis: Typical conditions employ POCl3 (1.2–2.0 equiv) and a tertiary amine (e.g., Et3N, 3–4 equiv) in CH2Cl2 or acetonitrile at 0 °C to rt, then warm as needed. Workup with aqueous bicarbonate minimizes acid byproducts. Odorous isocyanides demand stringent containment.
  • Reduction: Slow addition of amide to cooled LiAlH4 in anhydrous THF/Et2O, 0–25 °C, then standard Fieser workup. Monitor by GC or TLC (derivatize if needed).
  • Hydrolysis: 6 M HCl reflux or aq. NaOH at reflux; phase behavior may aid isolation of butylamine.
  • As solvent: Consider base compatibility; strong bases can deprotonate the N–H, altering reactivity.
• Analytical
  • GC or GC–MS suitable with on-column or PTV injection; derivatization (e.g., silylation of N–H) can improve peak shape. HPLC with UV at low wavelengths; amides absorb in deep UV.

Reaction Conditions

• Literature-guidance examples (not product specifications)
  • Dehydration to n-butyl isocyanide:
    • Typical reagents: POCl3 (1.3–2.0 equiv) with Et3N (3–5 equiv) or SOCl2 (excess) with catalytic DMF.
    • Solvents: CH2Cl2, MeCN, or toluene; 0 °C to rt initiation; may heat to 40–80 °C to drive completion.
    • Times/yields: 1–6 h; reported isolated yields often 60–90% depending on base and workup.
    • Tips: Exclude water; quench carefully; scrub vapors—isonitrides are intensely odorous.
  • Reduction to N-methylbutylamine:
    • Reagents: LiAlH4 (2–3 equiv) in anhydrous THF/Et2O; 0–25 °C, then gentle reflux as needed.
    • Times/yields: 2–16 h; good to excellent yields reported for secondary amide to amine reductions.
    • Alternatives: BH3·THF (0–25 °C) or catalytic hydrogenation with more forcing conditions.
  • Hydrolysis (cleavage to n-butylamine):
    • Acidic: 6 M HCl, reflux (3–8 h);
    • Basic: aq. NaOH, reflux; phase separation aids isolation of the amine (as free base after basification).
• Analytics and controls
  • Monitor by GC, GC–MS, or HPLC (UV 210–220 nm). Karl Fischer for water in anhydrous protocols. Residual chlorinating agents should be verified to be absent post-workup (e.g., chloride test, 31P NMR for phosphate byproducts in POCl3 routes).

Safety and Handling

• Item-specific (Product Data)
  • GHS/Signal word/H-statements/Pictograms: Not specified for this item; refer to SDS.
  • Storage conditions: Room temperature (Product Data). Keep container tightly closed.
• General safety considerations for N-alkyl formamides (literature/general)
  • Likely hazards: Irritant to skin, eyes, and respiratory tract; avoid inhalation of vapors and contact with skin/eyes. Heating can release irritating fumes (e.g., formic acid, amines).
  • PPE: Use chemical-resistant gloves (e.g., nitrile), lab coat, and safety glasses or face shield. Handle inside a fume hood to limit vapor exposure.
  • Incompatibilities: Strong oxidizers; strong acids or bases may promote hydrolysis; dehydrating agents (e.g., POCl3, SOCl2) react vigorously; avoid alkali metals.
  • Peroxide formation: Not an ether—peroxide formation is not a typical concern.
  • Spills: Absorb with inert material; avoid releases to drain; ventilate area. Dispose per local regulations.
  • First aid (summary; defer to SDS):
    • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
    • Skin: Remove contaminated clothing; wash with soap and water.
    • Eyes: Rinse cautiously with water for several minutes; remove contacts if present and easy; continue rinsing; seek medical advice.
    • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Transportation & fire
  • Combustibility: Combustible liquid; use CO2, dry chemical, or foam for extinguishing. Cool containers with water spray.

Solvent Selection

• Applicability
  • N-Butylformamide is primarily a building block/reagent, but it can serve as a polar, high-boiling, aprotic solvent for certain transformations where amide polarity/H-bonding is advantageous.
• Solvent characteristics (literature/general)
  • Polarity: Polar aprotic with significant hydrogen-bonding ability (acceptor) and moderate donor capacity (via N–H), higher cohesive energy than typical ethers/esters.
  • Boiling point: High (~200+ °C), enabling elevated-temperature reactions without pressure equipment.
  • Miscibility: Broad miscibility with polar organics; substantial water solubility.
• When to choose N-butylformamide
  • As a reaction medium for high-temperature nucleophilic substitutions, condensations, or cyclizations where DMF/NMP are also considered but a slightly less volatile amide is desired.
  • As a cosolvent to modulate polarity and hydrogen-bonding in challenging solubilization problems (salts, polar intermediates).
• Comparisons (general)
  • Versus DMF/NMP: Similar polarity; higher viscosity and boiling point; potentially lower volatility exposure. Reaction rates/mechanisms often comparable, but specific outcomes can differ due to H-bonding and sterics.
  • Versus DMSO: Similar polarity class but different donor/acceptor balance; DMSO lacks N–H and can behave differently with strong electrophiles/bases.
• Practical tips
  • Drying: If water-sensitive, dry over molecular sieves (3Å/4Å) or vacuum distill under reduced pressure. Verify water by KF.
  • Workup: High bp complicates removal; prefer liquid–liquid extraction or convert to a removable phase via derivatization when used as solvent.

Storage and Reconstitution

• Item-specific (Product Data)
  • Storage: Room temperature.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• General handling/stability (literature/general)
  • Shelf-life: Amides are typically stable under ambient conditions when protected from moisture and strong acids/bases. Minimize prolonged exposure to air to limit hydrolysis to butylamine/formic acid under extreme conditions.
  • Packaging: Store in tightly sealed amber glass or compatible HDPE. If used as a solvent/reagent for moisture-sensitive chemistry, keep over 3Å/4Å molecular sieves after opening.
  • Freeze–thaw: Not applicable; liquid at ambient conditions. No reconstitution required.
  • In-use guidance: If dryness is critical, verify water content by Karl Fischer before use. For analytical applications, pre-filter through PTFE (0.2 µm) if particulate contamination is suspected.
• Research use note
  • For research use only. Not for human or animal therapeutic or diagnostic use.

Structure and Identity

• Item-specific (Product Data)
  • Product name: N-Butylformamide (SKU: N1068065)
  • CAS: 871-71-6
  • InChIKey (as provided): 303690
  • Storage conditions: Room temperature
• Literature/Computed identifiers (for reference; verify against CoA/SDS)
  • Molecular formula (literature): C5H11NO
  • Molecular weight (literature): 101.15 g/mol
  • SMILES (literature): CCCCNC=O
  • InChI (literature): InChI=1S/C5H11NO/c1-2-3-4-6-5-7/h5H,2-4H2,1H3,(H,6,7)
  • InChIKey (literature): VBBCIYHIMJOSHG-UHFFFAOYSA-N
• Structural features (general chemistry description)
  • Functional groups: Secondary amide (formamide) with an N-butyl substituent; features a formyl carbonyl (–C(=O)H) conjugated to the amide nitrogen.
  • Polarity/H-bonding: Capable of hydrogen-bond donation (N–H) and acceptance (C=O), giving notable polarity relative to its C4 alkyl chain.
  • 2D description: A linear n-butyl chain (–CH3–CH2–CH2–CH2–) attached to an amide nitrogen (–NH–), which is bound to a formyl carbonyl (–C(=O)H). No rings, no stereocenters, and no halogens.
  • Resonance: Typical amide resonance (nN→π*CO) reduces basicity of the nitrogen and imparts partial double-bond character to the C–N bond.

Synthetic Utility

• Functional group leverage
  • The secondary amide engages typical amide chemistry: nucleophilic acyl substitution (under forcing conditions), reduction to amines, dehydration to nitriles/isocyanides (for formamides), and hydrolysis.
• Key transformations (literature/general)
  • Isonitrile synthesis: Dehydration of N-alkylformamides affords the corresponding isocyanides—central inputs to Ugi, Passerini (via post-functionalization), and related multicomponent reactions.
  • Reductive N-methylation: Reduction of the formamide carbonyl yields N-methylbutylamine, a useful intermediate for surfactants, ligands, and fine-chemicals.
  • Cross-coupling adjunct: The amide can serve as a directing group or temporary protecting group in C–H functionalization contexts after derivatization (more common with aryl amides, but aliphatic analogs can be explored in method development).
  • Transamidation/Amidation: Under catalytic activation (e.g., B(OCH3)3, Ti(IV), or Ni-catalyzed systems), can participate in exchange or condensation to build amide libraries.
• Retrosynthetic perspective
  • N-Butylformamide is a convergent node: either from butylamine + formic acid/activated formyl donors, or via formylation of butylamine with ethyl formate/CO/metal-catalyzed carbonylation. Its availability simplifies access to n-butyl isocyanide and N-methylbutylamine.
• Practical considerations
  • Control of water is crucial for dehydrations; base selection (Et3N, DIPEA) and temperature ramp strongly influence isocyanide yield and odor management. For reductions, choose hydride source and solvent for safety and chemoselectivity.

Target Specificity

• Not applicable.
  • This product is a small-molecule amide, not a biological targeting agent. No antigen/epitope, clone, or species reactivity information applies.