1-Aminocyclohexanecarbonitrile: Properties, Synthesis & Applications

1-Aminocyclohexanecarbonitrile is a cyclic alpha-aminonitrile compound serving as a versatile intermediate in organic synthesis, particularly in the preparation of amino acids, heterocycles, and bioactive pharmaceutical scaffolds.

Chemical Name

1-Aminocyclohexane-1-carbonitrile

Molecular Formula

C7H12N2

Molecular Weight

124.18 g/mol

Functional Class

Alpha-aminonitrile (cyclic)

Key Reaction Type

Strecker amino acid synthesis intermediate

Primary Applications

Pharmaceutical building block, heterocyclic synthesis, peptidomimetic research

Aladdin SKU

A589452

Chemical Identity and Structure

1-Aminocyclohexanecarbonitrile (also referred to as 1-aminocyclohexane-1-carbonitrile) is a cyclic alpha-aminonitrile in which both an amino group (–NH₂) and a nitrile group (–CN) are attached to the same quaternary carbon at the 1-position of the cyclohexane ring. Its molecular formula is C₇H₁₂N₂ with a molecular weight of approximately 124.18 g/mol.

The compound belongs to the broader class of alpha-aminonitriles, which are characterized by the geminal placement of an amine and a nitrile on a single carbon centre. This structural arrangement confers significant synthetic versatility, because the nitrile group can be hydrolysed to carboxylic acids or amides, reduced to amines, or elaborated into heterocyclic systems, while the amine provides a handle for further N-functionalization.

The quaternary carbon centre is fully substituted, making 1-Aminocyclohexanecarbonitrile a congested but conformationally constrained scaffold. The rigid cyclohexane ring imparts useful steric and conformational properties that are exploited in medicinal chemistry to control bioactive conformation.

Synthesis and Preparation

The most direct and historically significant route to 1-Aminocyclohexanecarbonitrile is the Strecker synthesis, a classic multicomponent reaction. In this approach, cyclohexanone is treated with ammonia (or an ammonium salt) and hydrogen cyanide (or a cyanide source such as TMSCN or KCN/HCl) to yield the alpha-aminonitrile in a single step. The reaction proceeds through formation of an imine (or iminium ion) intermediate, which subsequently undergoes nucleophilic addition of cyanide.

Alternative routes include:

• Reaction of cyclohexanone cyanohydrin with ammonia: The cyanohydrin of cyclohexanone can be aminated under pressure or with ammonia equivalents to give the target compound.
• From isocyanides: Alpha-isocyanato or alpha-isocyano cyclohexane precursors can be transformed to aminonitriles under appropriate conditions.
• Enzymatic approaches: Hydroxynitrile lyases have been investigated for the synthesis of chiral cyanohydrins, and analogous biocatalytic strategies may apply to aminonitrile formation.

In a laboratory or production context, careful control of pH, temperature, and the order of addition of reagents is critical, since HCN is highly toxic. Safe handling protocols, including working in a fume hood with appropriate personal protective equipment, are mandatory.

Research Applications

1-Aminocyclohexanecarbonitrile finds utility across several areas of synthetic and medicinal chemistry:

1. Amino Acid and Peptidomimetic Synthesis

Hydrolysis of the nitrile group under acidic or basic conditions yields 1-aminocyclohexane-1-carboxylic acid (also known as 1-aminocyclohexanecarboxylic acid or ACHC), a cyclic, quaternary alpha-amino acid. ACHC and its derivatives are well-established building blocks for peptidomimetics and conformationally constrained peptides, where the cyclohexane ring enforces specific backbone dihedral angles that can mimic beta-turns or helical structures in bioactive peptides.

2. Heterocyclic Chemistry

The bifunctional nature of 1-Aminocyclohexanecarbonitrile (bearing both a nucleophilic amine and an electrophilic nitrile) makes it an attractive substrate for the construction of nitrogen-containing heterocycles. Condensation reactions with carbonyl compounds, dicarbonyls, or electrophilic partners can furnish dihydropyrimidines, imidazolines, and related scaffolds of broad pharmaceutical interest.

3. Drug Discovery and Scaffold Design

Cyclic alpha-aminonitriles serve as bioisosteres and prodrug motifs for alpha-amino acids. The constrained cyclohexane ring has been exploited in the design of protease inhibitors, kinase modulators, and CNS-targeted compounds, where conformational rigidity aids selectivity. Researchers in fragment-based drug discovery also use such compact, functionalized cyclic scaffolds as starting fragments.

4. Polymer and Materials Chemistry

Alpha-aminonitrile monomers have been explored as precursors for functional polymers, including polyamides and polypeptide analogues, although this remains a more specialized application.

Handling, Safety and Storage

As an alpha-aminonitrile, 1-Aminocyclohexanecarbonitrile can slowly release hydrogen cyanide upon hydrolysis under strongly acidic or basic conditions. Researchers should treat the compound with appropriate caution:

• Personal Protective Equipment: Wear chemical-resistant gloves, safety goggles, and a laboratory coat. Work in a well-ventilated fume hood whenever handling the solid or solutions.
• Storage: Store in a tightly sealed container in a cool, dry, well-ventilated location away from strong acids, strong bases, and oxidising agents. Refrigerated storage (2–8 °C) is commonly recommended to retard decomposition; confirm specific conditions on the Certificate of Analysis supplied with the product.
• Disposal: Follow institutional and local regulations for disposal of nitrile-containing chemical waste. Do not pour down drains without appropriate neutralisation and verification of local limits.
• Emergency Procedures: In case of skin or eye contact, flush with copious water and seek medical attention. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use.

Always consult the current SDS for the most authoritative and up-to-date safety information specific to the supplied lot.

Quality Specifications and Ordering

Aladdin Scientific supplies 1-Aminocyclohexanecarbonitrile under SKU A589452. When evaluating the product for your research, consider the following quality parameters typically reported on the Certificate of Analysis (CoA):

• Purity: Assessed by GC or HPLC; confirm the minimum purity specification meets your application requirements before ordering.
• Appearance: Typically a white to off-white crystalline solid or powder.
• Identity Confirmation: NMR (¹H and ¹³C) and/or IR spectroscopy are standard identity tests.
• Lot-Specific CoA: Available on request or via the Aladdin Scientific website using the lot number printed on the label.

For bulk quantities, custom purity grades, or additional analytical data, contact Aladdin Scientific technical support or your regional sales representative. The product reference number BD278978 may be used to cross-reference equivalent catalogue entries across supplier databases.

Frequently asked questions

What is 1-Aminocyclohexanecarbonitrile used for in research?

1-Aminocyclohexanecarbonitrile is primarily used as a synthetic building block in organic and medicinal chemistry. It can be hydrolysed to yield the constrained amino acid 1-aminocyclohexane-1-carboxylic acid (ACHC), used in peptidomimetic research, or elaborated into nitrogen-containing heterocycles relevant to drug discovery.

How is 1-Aminocyclohexanecarbonitrile synthesised?

The compound is most commonly prepared via the Strecker synthesis, in which cyclohexanone reacts with ammonia and a cyanide source (such as HCN, KCN, or TMSCN) to give the alpha-aminonitrile directly. Alternative routes from the cyanohydrin of cyclohexanone are also documented.

Is 1-Aminocyclohexanecarbonitrile hazardous?

As a cyclic alpha-aminonitrile, the compound can release hydrogen cyanide upon hydrolysis under strongly acidic or basic conditions and should be handled with appropriate precautions, including use of a fume hood, chemical-resistant gloves, and safety goggles. Always consult the current Safety Data Sheet (SDS) before use.

What is the molecular weight of 1-Aminocyclohexanecarbonitrile?

The molecular formula of 1-Aminocyclohexanecarbonitrile is C7H12N2, giving a molecular weight of approximately 124.18 g/mol.

How should 1-Aminocyclohexanecarbonitrile be stored?

The compound should be stored in a tightly sealed container in a cool, dry, well-ventilated area, away from strong acids, bases, and oxidising agents. Refrigerated storage at 2–8 °C is generally recommended to retard decomposition; verify conditions on the product CoA.

References

1. Strecker, A. Ueber die künstliche Bildung der Milchsäure und einen neuen, dem Glycocoll homologen Körper. Justus Liebigs Ann. Chem. 1850, 75, 27–45.
2. Gante, J. Peptidomimetics — Tailored Enzyme Inhibitors. Angew. Chem. Int. Ed. Engl. 1994, 33, 1699–1720.
3. Seebach, D.; Matthews, J. L. beta-Peptides: a surprise at every turn. Chem. Commun. 1997, 2015–2022.
4. Aladdin Scientific. Product Page: 1-Aminocyclohexanecarbonitrile, SKU A589452. Aladdin Scientific Corp.

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