Methyl 4-hydrazinylbenzoate - ≥95% , CAS No.4510-12-7

CAS: 4510-12-7 Cat. No.: M1073272 Summenformel: C₈H₁₀N₂O₂ Molekulargewicht: 166.180

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥95%

Storage

Room temperature

Reinheit

≥95%

Namen und Kennungen

Kanonisches Lächeln

COC(=O)C1=CC=C(C=C1)NN

IUPAC Name

methyl 4-hydrazinylbenzoate

InChIKey

PUVXAQCVNJUHKG-UHFFFAOYSA-N

INCHI

1S/C8H10N2O2/c1-12-8(11)6-2-4-7(10-9)5-3-6/h2-5,10H,9H2,1H3

Molekulargewicht

166.180

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Benzoic acid esters
• Alternative Parents: Phenylhydrazines Benzoyl derivatives Methyl esters Monocarboxylic acids and derivatives Organopnictogen compounds Organooxygen compounds Organic oxides Hydrocarbon derivatives Hydrazines and derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Benzoate ester - Benzoyl - Phenylhydrazine - Methyl ester - Carboxylic acid ester - Carboxylic acid derivative - Monocarboxylic acid or derivatives - Organic nitrogen compound - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Hydrazine derivative - Organic oxide - Organopnictogen compound - Organic oxygen compound - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
• 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: 166.180 g/mol
• XLogP3: 1.500
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 166.074 Da
• Monoisotopic Mass: 166.074 Da
• Topological Polar Surface Area: 64.400 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 153.000
• 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 validated bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule reagent. For synthetic or derivatization uses, see Reaction Conditions for general procedure outlines. Always adapt to your specific substrates and verify with small-scale trials.

Biological Roles

This compound is intended for research and laboratory use only. It has no assigned biological role as supplied.

General biochemical context (literature):

• Hydrazine chemistry in bioconjugation: Hydrazines react with aldehydes (e.g., on oxidized glycans) to form hydrazones, enabling labeling or immobilization of biomolecules. Aryl hydrazines can be less reactive than aliphatic hydrazines but offer better stability; electron-withdrawing substituents (such as a para-ester) modulate pKa and nucleophilicity.
• Reversibility and stabilization: Hydrazones are reversible under acidic conditions but can be stabilized by reduction (NaBH3CN or catalytic hydrogenation) to secondary amines (reductive amination workflow).

Caveats:

• Hydrazine derivatives are typically cytotoxic and are used ex vivo/in vitro under controlled conditions; they are not suitable as nutrients or therapeutics.
• For any biological application, thoroughly remove residual reagent from conjugates and verify compatibility with biomolecules and buffers.

Buffer Applications

This item is not a buffering agent and is not used to control pH directly.

Practical note (for reactions in buffered media):

• Hydrazone formation with biomolecular aldehydes commonly employs mildly acidic buffers (acetate or citrate, pH ~4–6) to accelerate condensation, often with 10–50% water-miscible organic cosolvent (e.g., EtOH, DMF) to solubilize the aryl hydrazine. These are general literature guidelines; optimize empirically for your system.

Green Alternatives

While this product is a reagent/building block (not a solvent), greener-by-design considerations focus on minimizing hydrazine-associated hazards and solvent footprint in processes using it.

Greener considerations (literature/practice):

• Reagent substitution for carbonyl capture:
  • Alternatives such as aminooxy reagents (alkoxyamines) or semicarbazide can provide carbonyl derivatization with reduced toxicity compared to hydrazines; however, kinetics and selectivity differ (oxime formation often slower at neutral pH; may require aniline catalysis).
• Process intensification:
  • Run hydrazone formations in water-rich media (acetate/citrate buffers) with minimal organic cosolvent; consider microwave or flow to cut time/energy.
• Solvent selection hierarchy:
  • Prefer greener solvents (EtOH, i-PrOH, 2-MeTHF, CPME) over DMF/NMP/CH2Cl2 where compatible. For acylations, EtOAc or 2-MeTHF often replace DCM; for condensations, aqueous ethanol is effective.
• Waste and safety:
  • Minimize excess hydrazine-containing reagents; quench residues with oxidants under controlled conditions and segregate waste as hazardous.

Example comparison (general):

• Carbonyl ligation at pH 4–6
  • Using this aryl hydrazine: Fast kinetics; potential toxicity concerns; requires careful waste handling.
  • Using aminooxy reagent: Often safer profile; may need catalyst and longer times; products are oximes (E/Z issues) rather than hydrazones.

Pharmaceutical Uses

No pharmacopeial/excipient status or formulation grade is specified for this item; it is supplied for research use only.

Contextual, non-clinical uses (literature/practice):

• Synthetic intermediate: The para-ester and aryl hydrazine functionality make this compound a useful intermediate toward heterocycles (indoles via Fischer synthesis), azo dyes/pigments (post-diazotization), and diversified benzoates/benzoamides.
• Linker installation: The ester can be transformed to the acid and coupled to amines (amide formation), while the hydrazine can be derivatized or protected, enabling stepwise assembly of small-molecule libraries relevant to medicinal chemistry discovery.

No therapeutic or clinical claims are made or implied for this product.

Physical Properties

Item-specific physicochemical specifications are not provided in the Product Data for this SKU. Consult the CoA/Spec Sheet for authoritative values.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet. (Aryl hydrazines of this class are commonly crystalline solids; literature values vary by substituents.)
• Boiling point: Not applicable/rarely used (decomposes before boiling); not specified for this item.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable (solid) / Not specified for this item.
• Solubility (general guidance):
  • Expected to be soluble in polar organic solvents (e.g., DMSO, DMF, alcohols) due to the hydrazine and ester functionalities; limited to moderate solubility in nonpolar solvents; water solubility may be modest owing to aromatic core. These are qualitative, literature-based expectations, not item specs.
• pKa/logP (literature/general):
  • Aryl hydrazines typically exhibit basicity at the terminal –NH2 (conjugate acid pKa often in the 3–6 range for aryl diazenium ions) and weaker basicity at the aryl-bound nitrogen; exact values for this compound are not specified.
  • LogP expected to be moderate due to one ester and one hydrazine group; exact value not specified.

Always verify suitability and solubility empirically for your method; dry solvents can be advantageous for moisture-sensitive couplings involving the ester.

Quality and Grades

• Grade/Purity: 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 (general, for context):

• Research-grade aryl hydrazines are commonly offered with assay by HPLC/GC and control of related azo/azoxy impurities formed by oxidation. If HPLC-grade or “low UV-absorbing impurity” grades are required (e.g., analytical derivatization), ensure the UV background is suitable across your detection wavelength.
• For synthesis, limits on inorganic residues (metals), water, and residual solvents can influence reactivity (e.g., in diazotization or acylation). Verify these on the CoA for sensitive applications.
• Stabilizer implications: Some hydrazines may be shipped with trace acid scavengers or under inert gas to suppress oxidation; if present, this will be declared on the CoA and may affect downstream reactions (neutralize/remove as needed).

Recommendation: For carbonyl derivatization or Fischer indolization, select lots with low peroxide/oxidant content and confirm purity just before use.

Reaction and Applications

Methyl 4-hydrazinylbenzoate combines an aryl hydrazine with a methyl ester, enabling orthogonal reactivity useful in synthesis and derivatization.

Key application families (literature/practice):

• Carbonyl derivatization: Formation of hydrazones with aldehydes/ketones under mildly acidic conditions (pH ~4–6 or catalytic acid in organic solvents). Useful for analytical derivatization, purification handles, or as intermediates to Wolff–Kishner-type reductions (via hydrazones with aliphatic carbonyls) when appropriately configured.
• Fischer indole synthesis: Para-substituted phenylhydrazines engage ketones/aldehydes under Brønsted acid catalysis (e.g., H2SO4, TsOH) at 80–140 °C to form indoles; the para-ester can serve as a handle for further diversification or as an electron-withdrawing modulator of reactivity.
• Diazotization/azo coupling: Aryl hydrazines can be converted to diazonium species with nitrite in mineral acid at 0–5 °C, enabling azo dye formation with activated aromatics or phenols; control conditions to minimize over-oxidation.
• N-acylation and urea formation: Selective acylation at the terminal –NH2 using acyl chlorides/anhydrides gives N-acyl hydrazines; diacylation to ureas/semicarbazide-like motifs is possible under stronger/stoichiometric conditions.
• Ester transformations: The methyl ester can undergo hydrolysis (to the acid), transesterification, or amide coupling (after activation or via the acid chloride) to install diverse linkers.

Practical tips:

• Protecting-group strategy: If chemoselective transformations are needed, protect the hydrazine (e.g., Boc on terminal N) before manipulating the ester.
• Control oxidation: Work under inert atmosphere when feasible; add antioxidants/scavengers judiciously and avoid unnecessary exposure to air/heat.
• Monitoring: TLC/UPLC with UV at 254 nm is often effective; hydrazone formation shifts UV spectra—useful for reaction tracking.

Reaction Conditions

Typical conditions (general literature guidance; optimize per substrate):

• Hydrazone formation with aldehydes/ketones:
  • Solvent: EtOH, MeOH, or mixed aqueous buffer (acetate/citrate, pH 4–6) with 10–50% organic cosolvent (DMF/DMSO for poorly soluble partners).
  • Temperature/time: 20–50 °C, 0.5–12 h depending on carbonyl electrophilicity; remove water (molecular sieves) to drive equilibrium in nonaqueous media.
  • Additives: Catalytic acid (AcOH, TsOH) or aniline catalysts for challenging substrates; monitor by TLC/UPLC.
• Fischer indole synthesis:
  • Reagents: Carbonyl partner (often ketone), strong Brønsted acid (H2SO4, TsOH) or Lewis acid, optionally polyphosphoric acid.
  • Solvent/conditions: Neat, toluene, dioxane, or acid media; 80–140 °C for 2–24 h; inert atmosphere recommended.
• N-acylation (to N-acyl hydrazines/ureas):
  • Reagents: Acyl chlorides/anhydrides, base (Et3N, DIPEA, pyridine).
  • Solvent: CH2Cl2, THF, MeCN, or EtOAc; 0–25 °C, 0.5–4 h. Use 1.0–1.1 equiv for monoacylation; excess drives diacylation.
• Ester hydrolysis and amide coupling:
  • Hydrolysis: Aqueous NaOH or K2CO3 in MeOH/THF/H2O, 0–25 °C, then acidify to give the acid.
  • Coupling: HATU/HBTU/EDC (with HOAt/HOBt or Oxyma) in DMF/DCM; 0–25 °C, 1–12 h. Protect hydrazine if chemoselectivity is critical.
• Diazotization/azo coupling:
  • Diazotize at 0–5 °C with NaNO2 in HCl; couple with activated aromatics/phenols in mildly basic media. Strict temperature control to limit side reactions.

Yields are substrate-dependent and not specified for this item.

Safety and Handling

Hazard classification details (GHS, H-statements, pictograms, signal word) are not provided in the Product Data for this item. Refer to the product-specific Safety Data Sheet (SDS) for authoritative safety information.

General, chemistry-informed guidance for aryl hydrazines and related esters (not a substitute for the SDS):

• Likely hazards: Toxic if swallowed/inhaled, skin/eye irritation, potential sensitization; hydrazine derivatives can be reducing and may be harmful if absorbed through skin. Avoid inhalation of dust and contact with skin/eyes.
• PPE: Use lab coat, safety goggles, and appropriate chemically resistant gloves (e.g., nitrile). Handle in a fume hood to minimize exposure.
• Incompatibilities: Strong oxidizers (hydrazines are readily oxidized), nitrosating agents (risk of diazotization), strong acids/bases (may induce decomposition, hydrolysis of the ester, or uncontrolled reactions). Keep away from ignition sources during scale-up.
• Special risks: Aryl hydrazines can undergo diazotization with nitrite in acid; avoid unintended contact with nitrite sources in acidic media. Oxidation to azoxy/azo species is possible on exposure to air/oxidants.
• First aid (overview; defer to SDS):
  • Skin/eye contact: Rinse with plenty of water for at least 15 minutes; remove contaminated clothing; seek medical attention.
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill response: Avoid dust formation, absorb with inert material, and dispose of as hazardous waste per institutional and local regulations.

Solvent Selection

This product is a multifunctional aryl hydrazine/ester building block rather than a solvent. Solvent choice should be tailored to the intended transformation.

General solvent guidance (literature/practice):

• Polarity and miscibility:
  • Polar aprotic solvents (DMSO, DMF, NMP, MeCN) dissolve aryl hydrazines well and support hydrazone formation, acylation, and coupling steps.
  • Alcohols (MeOH, EtOH, i-PrOH) are often effective for condensations with carbonyls; beware of transesterification of the methyl ester in basic, alcoholic media.
  • Nonpolar solvents (toluene, dioxane) may be used for Fischer indole synthesis under acidic conditions at elevated temperatures.
• Water compatibility: Hydrazone formations can be run in mixed aqueous–organic buffers at pH ~4–6; solubilizing co-solvents (DMSO/DMF) are often needed.
• Choosing among options:
  • For hydrazone/oxime-type ligations: Aqueous acetate/citrate buffer with 10–50% MeOH, EtOH, or DMF; optionally add aniline catalysts for aldehyde partners (note: the reagent itself is a hydrazine and is reasonably nucleophilic).
  • For acylation of the hydrazine: Use anhydrous CH2Cl2, THF, or MeCN with base (e.g., Et3N, DIPEA) at 0–25 °C.
  • For saponification/amidation of the ester: Aqueous base (NaOH, K2CO3) in MeOH/THF for hydrolysis; DMF or DCM with coupling reagents for amide formation post-hydrolysis.

Always dry solvents for moisture-sensitive steps and monitor for side reactions (over-acylation to ureas, transesterification).

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not applicable to solids in the strict sense; for use, prepare solutions freshly in a suitable solvent (e.g., DMSO, DMF, alcohols) under clean, dry conditions.

Good practice (general):

• Protect from moisture and air to minimize oxidation of the hydrazine; store tightly closed in the original container, preferably in a desiccator or with inert gas headspace if available.
• If preparing stock solutions, use anhydrous solvent, filter if needed (0.2 µm PTFE), and store aliquots in amber vials at 2–8 °C or −20 °C as appropriate to your solvent system. Avoid repeated freeze–thaw of solutions.
• Inspect material periodically for discoloration (possible oxidation) and verify purity by HPLC/UPLC before critical applications.

Research Use Note: For research use only.

Structure and Identity

Methyl 4-hydrazinylbenzoate is an aryl hydrazine bearing a para-substituted hydrazinyl (-NH–NH2) group on a methyl benzoate ring.

• SKU: M1073272
• Product name: Methyl 4-hydrazinylbenzoate
• CAS: 4510-12-7
• PubChem CID (literature): 408928
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (literature/computed): C8H10N2O2
• Molecular weight (literature/computed): 166.18 g/mol

Structural features (general description):

• Aromatic ring: a benzene core substituted para to each other by an electron-withdrawing methyl ester (–CO2Me) and an electron-donating hydrazinyl (–NH–NH2) group.
• Functional groups: aryl hydrazine (nucleophilic, can form hydrazones; prone to diazotization), methyl ester (electrophilic carbonyl, amenable to hydrolysis, transesterification, or amidation after activation).
• Stereochemistry: none (achiral molecule).
• 2D structure in words: a benzene ring with –COOCH3 at the 1-position and –NH–NH2 at the 4-position (para relationship), connected through sp2 carbons of the ring.

Note: Identity parameters not explicitly listed under Product Data (SMILES, full InChIKey) are provided here only as general literature/computed descriptors and are not item-specific specifications.

Synthetic Utility

Functional group leverage:

• Aryl hydrazine (–NH–NH2):
  • Nucleophilic addition to carbonyls → hydrazones; platform for further transformations (reductions, cyclizations).
  • Electrophile capture: Acylation (acyl chlorides/anhydrides) to mono- or diacylated derivatives; carbamoylation with chloroformates to urethanes.
  • Diazotization/coupling to access azo derivatives (dyes, ligands) under controlled conditions.
• Methyl ester (–CO2Me):
  • Hydrolysis to 4-hydrazinylbenzoic acid, then amide coupling (EDC/HOBt, HATU, or acid chloride route).
  • Transesterification to other alkyl esters (acidic/basic catalysis) to tune solubility or reactivity.

Retrosynthetic value:

• Serves as a para-substituted phenylhydrazine synthon with a latent carboxyl handle for late-stage diversification (convertible to acid/amide). Useful in diversity-oriented synthesis where orthogonal manipulations are needed.

Named-reaction relevance (literature):

• Fischer indole synthesis with ketones/aldehydes (acidic, thermal conditions).
• Japp–Klingemann-type sequences (via diazotization and coupling with β-dicarbonyls), adjusted for hydrazine/azo chemistry.

Selectivity notes:

• Terminal –NH2 is typically more nucleophilic than the aryl-bound –NH; control acylation stoichiometry and base to avoid over-acylation. Protect if ester chemistry requires strong bases.

Target Specificity

Not applicable. This product is a small-molecule reagent and does not possess biological target specificity (no antigen/epitope/clone/isotype information). Refer to Reaction & Applications and Synthetic Utility for relevant use cases.