4-Hydroxy-1-methylcyclohexanecarboxylic acid - ≥97% , CAS No.76657-91-5

CAS: 76657-91-5 Cat. No.: H1020555 Fórmula: C₈H₁₄O₃ Peso molecular: 158.190

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Especificações e pureza

≥97%

Condições de armazenamento de armazenamento

Room temperature

Pureza

≥97%

Nomes e identificadores

• Sorrisos canónicos: CC1(CCC(CC1)O)C(=O)O
• IUPAC Name: 4-hydroxy-1-methylcyclohexane-1-carboxylic acid
• InChIKey: NRJADRDKYOBCKH-UHFFFAOYSA-N
• INCHI: 1S/C8H14O3/c1-8(7(10)11)4-2-6(9)3-5-8/h6,9H,2-5H2,1H3,(H,10,11)
• Peso molecular: 158.190

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Alcohols and polyols
        • Level5 Secondary alcohols
          • Level6 Cyclohexanols

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Alcohols and polyols
• Intermediate Tree Nodes: Secondary alcohols
• Direct Parent: Cyclohexanols
• Alternative Parents: Cyclic alcohols and derivatives Monocarboxylic acids and derivatives Carboxylic acids Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aliphatic homomonocyclic compounds
• Substituents: Cyclohexanol - Cyclic alcohol - Monocarboxylic acid or derivatives - Carboxylic acid - Carboxylic acid derivative - Organic oxide - Hydrocarbon derivative - Carbonyl group - Aliphatic homomonocyclic compound
• Descrição: This compound belongs to the class of organic compounds known as cyclohexanols. These are compounds containing an alcohol group attached to a cyclohexane 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

Propriedades químicas e físicas

• Peso molecular: 158.190 g/mol
• XLogP3: 0.700
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 158.094 Da
• Monoisotopic Mass: 158.094 Da
• Topological Polar Surface Area: 57.500 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 157.000
• 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 assay or bioanalytical application protocols are specified for this item. As a general laboratory chemical, usage depends on the intended synthetic transformation.

General handling (chemistry-focused):

• Prepare stock solutions in DMF, DMSO, MeOH, or EtOH as needed for reactions; filter if particulates are present.
• For amide couplings, pre-dry solvents and glassware; consider forming the activated ester (e.g., NHS ester) prior to introducing sensitive amines or aqueous components.
• For purification, if strong tailing occurs on silica due to acidity, convert transiently to a methyl/benzyl ester or add a small percentage of AcOH or Et3N to the eluent.

For any analytical or biological protocols, develop and validate conditions specific to your system; consult the CoA for purity and any lot-specific considerations.

Biological Roles

Item-specific biological activities or roles are not provided and should not be inferred. The compound is offered for research use as a synthetic building block.

General biochemistry context (literature-based):

• Aliphatic hydroxy acids can interact with metabolic enzymes (e.g., dehydrogenases) after suitable derivatization, but 4-hydroxy-1-methylcyclohexanecarboxylic acid is a non-natural, saturated cyclohexane derivative without a known endogenous role.
• The carboxylate form at physiological pH would be anionic; permeability and transporter interactions (e.g., monocarboxylate transporters) depend on structural recognition and are not established for this scaffold.
• The secondary alcohol at C4 offers a handle for bioconjugation (e.g., carbonate/carbamate linkages) in biochemical probe synthesis; any biological effects would arise from the conjugate rather than the parent acid.

No clinical or therapeutic claims are made. For any biological testing, determine purity, stereochemical composition, and counterion state, as these factors can influence in vitro assay outcomes.

Buffer Applications

This compound is not a standard laboratory buffer. It lacks a defined conjugate base/acid pair suitable for high-capacity buffering across a broad range.

General note (literature):

• Carboxylic acids buffer weakly near their pKa. For aliphatic carboxylic acids, pKa is typically ~4.5–4.9. If used transiently to adjust pH in specialized systems, anticipate low buffering capacity and potential precipitation in low-ionic-strength media.
• For aqueous handling, dissolution as the carboxylate salt (e.g., sodium salt prepared in situ with NaHCO3) may improve solubility. Verify compatibility with your biological system.

Recommendation: Employ standard buffers (e.g., acetate pH 3.8–5.8, MES pH 5.5–6.7, phosphate pH 6.0–8.0) for controlled pH applications. Use this compound primarily as a synthetic intermediate rather than a buffering agent.

Green Alternatives

While the compound itself is a substrate/reagent rather than a solvent, greener choices can be made for reactions and workups involving this hydroxy acid.

Greener solvent choices (general guidance):

• Replace chlorinated solvents where feasible:
  • Use ethyl acetate, 2-MeTHF, or MeCN instead of CH2Cl2 for Steglich or DCC/DMAP esterifications (verify solubility).
  • Use 2-MeTHF or CPME as greener ethers in reductions or protections (water-tolerant and lower peroxide tendency than THF/Et2O; literature comparisons).
• Switch from DMF/NMP to MeCN, EtOAc, propylene carbonate, or green esters when coupling solubility allows.

Reagent considerations:

• Favor carbodiimide-free couplings (e.g., CDI) or water-compatible EDC with catalytic DMAP over DCC to reduce urea waste.
• Consider enzymatic esterifications in organic media or solvent-free conditions when selectivity allows.

Small comparison (general):

• Process aspect | Conventional | Greener alternative | Trade-offs
• Coupling solvent | DMF/NMP | MeCN/EtOAc/2-MeTHF | May reduce solubility; monitor rate
• Esterification | CH2Cl2 + DCC/DMAP | EtOAc + EDC/DMAP or solvent-free | Heat control, water removal needed
• Reduction of acid | LiAlH4 (Et2O/THF) | Borane complexes in 2-MeTHF or catalytic hydrogenation of esters | Selectivity and safety profiles differ

Waste minimization:

• Plan protection strategies to minimize steps; telescoping activation/coupling and in situ ester formation can reduce solvent usage and workups.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item. It is supplied for research use as a small-molecule building block.

General formulation/manufacturing context (non-clinical):

• Intermediate in API synthesis: The carboxylic acid can be converted to amides/esters, and the ring alcohol can be derivatized, enabling preparation of sp3-rich API candidates and prodrugs in medicinal chemistry.
• Prodrug strategies (chemistry-only): Esterification of the acid or carbonate formation at the alcohol can modulate lipophilicity and stability for exploratory structure–property studies. Any in vivo/clinical implications are outside scope.
• Salt formation: Although aliphatic carboxylic acids readily form salts (e.g., Na+, K+, amine salts), such salts would be investigational and not standardized unless specified.

Note: No medical or therapeutic claims are made. For GMP or regulatory pathways, dedicated quality packages, impurity controls, and stereochemical specifications would be required; these are not specified for this catalog item.

Physical Properties

Item-specific physical specifications are not provided in the product data. The following are general/literature-oriented notes to aid method development; they are not product specifications.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting/Boiling Point: Not specified for this item; refer to CoA/Spec Sheet. Hydroxy-substituted cyclohexanecarboxylic acids are commonly crystalline solids (literature), but precise MP depends on stereochemistry and purity.
• Density/Refractive Index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general behavior):
  • Expected to be sparingly soluble in water in neutral form; readily soluble in basic aqueous media as the carboxylate (literature behavior of aliphatic carboxylic acids).
  • Good solubility in polar organic solvents (MeOH, EtOH, acetone, acetonitrile) and strong dipolar aprotics (DMF, DMSO) (literature).
  • Limited solubility in nonpolar hydrocarbons (hexanes, toluene) unless converted to esters or salts (literature).
• pKa (carboxyl, literature estimate): ~4.5–4.9 for aliphatic cyclohexanecarboxylic acids; the 4‑OH may exert a modest inductive effect. Use experimental determination for exact work.
• logP/logD: Not specified for this item; refer to CoA/Spec Sheet. Presence of both –OH and –CO2H reduces hydrophobicity versus alkyl cyclohexanes (literature trend).

Important: For validated numerical specifications (MP, water content, UV cutoff, heavy metals, etc.), consult the item’s CoA/Spec Sheet; do not substitute the above generalities for specifications.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet for assay, residual solvents, and impurity profiles.

Guidance on interpreting typical grades (general information):

• Research grade / ≥95–98% assay (typical for building blocks): Suitable for most synthetic applications, method development, and SAR work. Trace water and residual solvents are common considerations for acids/alcohols; verify by KF/GC as needed.
• HPLC grade (for solvents) / LC-MS grade (for analytes): Not applicable unless explicitly stated. For this solid building block, low-UV-absorbing impurities are relevant only if used as an analytical standard.
• Stabilizers/Inhibitors: None are indicated for this item. If present in a specific lot, stabilizers would be declared on the CoA and may affect downstream reactions (e.g., acid-sensitive steps).

Recommendations:

• Request a CoA for your lot to confirm assay, water content, residual solvents, and any stereochemical composition (if controlled).
• For stereochemistry-sensitive work, consider chiral HPLC or derivatization to determine enantiomeric/diastereomeric composition if not specified by the lot documentation.

Reaction and Applications

As a bifunctional aliphatic building block, 4-hydroxy-1-methylcyclohexanecarboxylic acid supports orthogonal derivatizations at the acid and alcohol.

Key application families (general/literature):

• Carboxyl activation and coupling: Formation of amides (HATU, EDC·HCl, DIC/HOAt/HOBt) and esterifications (Fischer, Steglich with DCC/DMAP). Acid chlorides via SOCl2 or (COCl)2 for further acylations.
• Alcohol transformations: Protection as silyl ethers (TBS/TBDPS), benzylation, or carbonate formation; Mitsunobu inversion to form O–alkyl derivatives; oxidation (e.g., Dess–Martin, PCC) to the corresponding ketone at C4 (secondary alcohol).
• Reductions: Carboxylic acid to alcohols via LiAlH4 or to aldehydes via Borane–THF or DIBAL-H on derivatives (e.g., esters). Chemoselectivity control may require protecting the ring alcohol.
• Halogenation/activation: Convert C4–OH to mesylate/tosylate for substitution/elimination sequences enabling further ring functionalization.
• Conformational/chemosite selectivity: The cyclohexane chair places 4‑OH axial/equatorial depending on conditions; selectivity in substitution or protection may be conformation-dependent (literature note).

Use cases:

• Medicinal chemistry: Scaffold for saturated (sp3-rich) analogs; diversify acid as amide/ester, and tune polarity via the C4 position.
• Materials/monomer precursor: Esterification affords diester cross-linkers when combined with diols/diacids (general concept).

Practical tips:

• Dry solvents and maintain anhydrous conditions for coupling chemistry; pre-form active esters (e.g., NHS esters) to couple with amines in aqueous-compatible media.
• For purification, transient protection (e.g., methyl ester) can simplify chromatography and improve recoveries.

Reaction Conditions

The following conditions are general literature guidance for molecules bearing a carboxylic acid and a secondary alcohol on a cyclohexane ring. They are not specifications for this item.

• Amide coupling:
  • HATU (1.1–1.5 eq), amine (1.2–2.0 eq), DIPEA (2–4 eq) in DMF or MeCN, 0–25 °C, 1–12 h. Typical isolated yields: 70–95% (substrate-dependent).
  • EDC·HCl (1.2–1.5 eq) + HOAt/HOBt or Oxyma (1.2–1.5 eq), base (DIPEA), DCM/DMF, 0–25 °C.
• Esterification:
  • Fischer: ROH (solvent, excess), catalytic H2SO4 or p‑TsOH, reflux, Dean–Stark or 3Å sieves; 4–24 h.
  • Steglich: DCC (1.2 eq), DMAP (0.1 eq), ROH (1.2–2.0 eq) in DCM or EtOAc, 0 °C to rt, 2–18 h.
• Acid chloride formation: SOCl2 (3–5 eq), catalytic DMF, DCM or neat, 0 °C to reflux, 1–3 h; follow by amide/ester formation.
• Alcohol protection: TBSCl (1.2–1.5 eq), imidazole (2 eq), DMF or DCM, 0–25 °C, 2–6 h. Benzylation: BnBr/NaH (THF), 0–25 °C.
• Alcohol oxidation to ketone: Dess–Martin periodinane (1.3 eq) in DCM, 0–25 °C, 0.5–3 h; or PCC (1.5 eq) in DCM, 25 °C, 1–6 h.
• Reduction of carboxyl to alcohol: LiAlH4 (2–3 eq) in THF or 2‑MeTHF, 0 °C to reflux, 1–4 h; quench carefully. Alternatively, esterify first, then reduce with NaBH4/catalyst for milder conditions.
• Mitsunobu substitution (for inversion at C4): DEAD/DIAD (1.2 eq), PPh3 (1.2 eq), nucleophile (1.5–2 eq), THF/TOluene, 0–25 °C, 1–6 h.

Monitoring and workup:

• TLC/HPLC for reaction progress; neutralize acids/bases carefully. For silica chromatography, small % of AcOH or Et3N can mitigate tailing of acidic/basic products.

Safety and Handling

Always consult the SDS for authoritative safety information. Item-specific GHS details were not provided in the product data.

• GHS/CLP classification: Not specified for this item; refer to SDS.
• Signal word / H-statements / Pictograms: Not specified for this item; refer to SDS.

General laboratory precautions for carboxylic acids bearing alcohol groups (literature-based):

• Irritation/Corrosivity: Aliphatic carboxylic acids can be skin/eye irritants; secondary alcohols can also irritate mucous membranes. Avoid inhalation of dust/particles and contact with skin/eyes.
• PPE: Lab coat, safety glasses or goggles, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to avoid exposure to vapors, aerosols, or dust.
• Incompatibilities:
  • Strong oxidizers (risk of exothermic reaction).
  • Strong bases and carbonates will neutralize the acid (CO2 evolution possible). Form reactive acid chlorides when treated with thionyl chloride/oxalyl chloride—handle with appropriate controls.
  • Dehydrating agents and strong acids can promote esterification or dehydration.
• First aid overview:
  • Skin/eye contact: Rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; seek medical attention.
• Fire safety: Organic solids may burn; use CO2, dry chemical, or foam. Combustion can produce CO/CO2.
• Waste disposal: Dispose according to local regulations; segregate from strong oxidizers and bases.

Note: No evidence of peroxide formation risk (no ether functionality). Defer to the SDS for definitive hazards.

Solvent Selection

This compound is a polar, hydrogen-bonding small molecule (carboxylic acid + secondary alcohol). Solvent choice depends on the task (reaction, purification, or formulation).

• Polarity class (general): Polar protic (as solute) with capacity for H-bond donation and acceptance; behaves well in polar protic and polar aprotic media.
• Preferred dissolution media (literature practice):
  • Strong dipolar aprotic: DMF, DMSO, NMP – excellent for amide couplings/activations.
  • Polar protic: MeOH, EtOH, i-PrOH – useful for esterifications and stock solutions.
  • Moderately polar aprotic: EtOAc, acetone, MeCN – good for extractions and many transformations.
  • Aqueous basic solutions (e.g., NaHCO3/Na2CO3) to dissolve as the carboxylate salt.
• Limited solubility expected in nonpolar hydrocarbons (hexanes, heptane) unless derivatized (e.g., as esters) (literature behavior).

Selection tips:

• For amide couplings, choose DMF or MeCN to maximize solubility and minimize competing transesterification.
• For esterifications (Fischer), use the corresponding alcohol as solvent with acid catalysis; remove water via Dean–Stark or molecular sieves.
• For chromatography, start with EtOAc/hexanes; if tailing occurs due to acidity, add 0.1–1% acetic acid or switch to MeOH/CH2Cl2 mixtures. Alternatively, convert to a neutral ester derivative for purification.

Small comparison (general):

• DMF vs DCM: DMF dissolves salts and supports carbodiimide couplings; DCM offers ease of removal but poorer solubility for polar acids.

Storage and Reconstitution

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

General guidance:

• Store in a tightly closed container, protected from moisture and strong oxidizers/bases. If long-term storage is planned, consider desiccation to minimize hydrolysis/esterification side reactions in moist environments.
• If stereochemistry is critical, minimize prolonged exposure to strong acids/bases that might promote epimerization at activated centers.

Reconstitution/solubilization (general):

• Dissolve in common polar solvents such as DMF, DMSO, MeOH, EtOH, acetone, or EtOAc. For aqueous applications, adjust to basic pH (e.g., with NaHCO3/NaOH) to form the carboxylate and enhance solubility.
• Filter solutions (0.2–0.45 µm) for particulate removal before sensitive applications.
• Prepare fresh solutions for moisture-sensitive coupling reactions; avoid prolonged storage in reactive solvents (e.g., alcohols) if free acid integrity must be preserved.

Note: For definitive stability data (e.g., shelf life, impurity growth, water content), consult the item-specific CoA/Spec Sheet. Product is for research use only.

Structure and Identity

A bifunctional cyclohexane building block bearing a carboxylic acid and a secondary alcohol on the ring, with a methyl substituent at C1 and a hydroxyl at C4.

• Product Name: 4-Hydroxy-1-methylcyclohexanecarboxylic acid
• CAS: 76657-91-5
• CID: 13236237
• SKU: H1020555
• InChIKey (as provided): 245987
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula (literature inference): C8H14O3
• Molecular Weight (literature calculation): ~158.19 g/mol

Structural features (general/literature):

• Ring system: Saturated cyclohexane.
• Functional groups: One carboxylic acid (–CO2H) at C1, one secondary alcohol (–OH) at C4, and a methyl substituent at C1.
• Stereochemistry: The C1 center is stereogenic in 1-methylcyclohexanecarboxylic acid; the additional 4‑OH substituent disrupts ring symmetry, so mixtures of stereoisomers (at least enantiomers, potentially diastereomers due to conformers) are possible unless otherwise specified. No stereochemical specification is provided for this item.
• 2D description: A cyclohexane ring bearing at C1 both a –CO2H substituent and a –CH3 (geminal substitution at C1), and at C4 (para to C1 on the ring) a –OH substituent. The acid carbonyl provides one site of unsaturation; the ring is otherwise saturated.

Notes:

• Item-specific identifiers not listed above are not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

The combination of a carboxylic acid and a secondary alcohol on a cyclohexane ring provides orthogonal vectors for diversification.

Strategic features (general/literature):

• Bidirectional elaboration:
  • Acid handle → amides, esters, acyl azides, anhydrides, or acid chlorides.
  • C4–OH → ethers, carbonates, carbamates, sulfonates (Ms/Ts), or oxidation to ketone.
• Functional group compatibility: The saturated ring tolerates hydrogenation, radical conditions, and many metal-catalyzed steps after suitable protection of acid/alkoxy groups.
• Stereochemical control: The C1 center (bearing –CO2H and –CH3) is stereogenic; selective transformations at C4 can be influenced by axial/equatorial orientation—protecting groups (e.g., TBS vs TBDPS) may show different selectivities.
• Retrosynthetic disconnects:
  • From corresponding methylcyclohexanone via aldol/oxidation–reduction sequences and carboxylation.
  • From ring hydroxylation of 1‑methylcyclohexanecarboxylate derivatives (e.g., via directed C–H oxidation) followed by hydrolysis.

Typical transformations:

• Amide coupling to generate diversified libraries (HATU/DIPEA in DMF/MeCN).
• Selective oxidation of secondary alcohol to ketone enabling further α‑functionalization.
• Intramolecular tactics: Conversion of the alcohol to a leaving group permits cyclization or bicyclic motif construction (substrate-dependent; verify feasibility).

Overall, this scaffold is well-suited to build sp3-rich chemical space with tunable polarity.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological targeting reagent (e.g., antibody, enzyme inhibitor with validated target, or ligand with defined selectivity). No target, epitope, clone, isotype, or species reactivity data are provided for this item.