N-methylcyclohexylamine chemical properties and applications in organic synthesis

Introduction to N-Methylcyclohexylamine

N-Methylcyclohexylamine (NMCHA) is an important organic compound with the molecular formula C7H15N. It is a colorless liquid with a characteristic amine odor. NMCHA is widely used in various industrial and research applications due to its unique chemical properties and reactivity. This article aims to provide a comprehensive overview of the chemical properties of N-methylcyclohexylamine and its applications in organic synthesis, including detailed product parameters, reaction mechanisms, and practical examples.

Chemical Properties of N-Methylcyclohexylamine

Physical Properties

Property	Value
Molecular Formula	C7H15N
Molecular Weight	113.20 g/mol
Appearance	Colorless liquid
Odor	Amine-like
Melting Point	-65°C
Boiling Point	154°C
Density	0.84 g/cm³ at 20°C
Refractive Index	1.426 (at 20°C)
Solubility in Water	10 g/100 mL at 20°C
Flash Point	46°C
Autoignition Temperature	320°C

Chemical Structure

N-Methylcyclohexylamine consists of a cyclohexane ring with a methyl group attached to one of the nitrogen atoms. The structure can be represented as:

[ text{C}6text{H}{11}text{CH}_3text{NH}_2 ]

Reactivity

1. Basicity: NMCHA is a secondary amine and exhibits moderate basicity. It can accept protons from acids to form ammonium salts.

   [ text{C}7text{H}{15}text{N} + text{H}^+ rightarrow text{C}7text{H}{15}text{NH}^+ ]

2. Nucleophilicity: As a nucleophile, NMCHA can participate in substitution reactions, particularly in SN2 reactions where it attacks electrophilic carbon centers.

3. Reduction and Oxidation: NMCHA can undergo reduction to form N-methylcyclohexylamine derivatives and oxidation to form N-methylcyclohexanone or other nitrogen-containing compounds.

Synthesis of N-Methylcyclohexylamine

N-Methylcyclohexylamine can be synthesized through several methods, each with its own advantages and limitations.

Method 1: Methylation of Cyclohexylamine

One common method involves the methylation of cyclohexylamine using methyl iodide or dimethyl sulfate.

[ text{C}6text{H}{11}text{NH}_2 + text{CH}_3text{I} rightarrow text{C}7text{H}{15}text{N} + text{HI} ]

Method 2: Reduction of N-Methylcyclohexanone

Another approach is the reduction of N-methylcyclohexanone using hydrogen gas over a catalyst such as palladium on carbon.

[ text{C}7text{H}{13}text{NO} + text{H}_2 rightarrow text{C}7text{H}{15}text{N} + text{H}_2text{O} ]

Applications in Organic Synthesis

N-Methylcyclohexylamine finds extensive use in organic synthesis due to its versatile reactivity. Some key applications include:

1. Catalysts in Polymerization Reactions

NMCHA can serve as a catalyst in the polymerization of various monomers, particularly in the formation of polyamides and polyurethanes. Its basicity helps in the initiation and propagation steps of these polymerizations.

2. Chiral Auxiliaries

In asymmetric synthesis, NMCHA can act as a chiral auxiliary to control the stereochemistry of products. For example, it can be used in the enantioselective synthesis of amino acids and other chiral molecules.

3. Protecting Groups

NMCHA can be used as a protecting group for carbonyl groups in organic synthesis. It forms stable imines that can be easily hydrolyzed under acidic conditions to regenerate the original carbonyl compound.

4. Solvent and Co-solvent

Due to its solubility in both polar and non-polar solvents, NMCHA can be used as a solvent or co-solvent in various synthetic reactions. It is particularly useful in reactions involving sensitive intermediates that require a controlled environment.

Reaction Mechanisms

Nucleophilic Substitution (SN2)

NMCHA can participate in SN2 reactions, where it acts as a nucleophile attacking a substrate with a good leaving group. For example:

[ text{C}7text{H}{15}text{N} + text{R-X} rightarrow text{C}7text{H}{15}text{NR} + text{X}^- ]

Acid-Base Reactions

As a base, NMCHA can deprotonate weak acids, forming stable salts. This property is useful in acid-catalyzed reactions and in the preparation of certain organic compounds.

[ text{C}7text{H}{15}text{N} + text{HA} rightarrow text{C}7text{H}{15}text{NH}^+ text{A}^- ]

Practical Examples

Example 1: Synthesis of N-Methylcyclohexylamine from Cyclohexylamine

Reagents: Cyclohexylamine, Methyl iodide, Potassium carbonate

Procedure:

1. Dissolve cyclohexylamine in anhydrous acetone.
2. Add potassium carbonate to neutralize any residual acid.
3. Slowly add methyl iodide dropwise while stirring.
4. Heat the mixture to reflux for 2 hours.
5. Cool the mixture and filter to remove inorganic salts.
6. Distill the filtrate to obtain pure N-methylcyclohexylamine.

Example 2: Use of NMCHA in Asymmetric Synthesis

Reagents: N-Methylcyclohexylamine, Chiral catalyst, Aldehyde, Ketone

Procedure:

1. Prepare a solution of the aldehyde and ketone in a suitable solvent.
2. Add the chiral catalyst and N-methylcyclohexylamine.
3. Stir the mixture at room temperature for 24 hours.
4. Quench the reaction with water and extract the product using an organic solvent.
5. Purify the product by column chromatography.

Safety and Handling

N-Methylcyclohexylamine is a flammable liquid and should be handled with care. It is important to store it in a well-ventilated area away from heat and ignition sources. Protective equipment such as gloves, goggles, and a lab coat should be worn when handling this compound. In case of spills, absorb the liquid with inert material and dispose of it according to local regulations.

Conclusion

N-Methylcyclohexylamine is a valuable compound in organic synthesis due to its unique chemical properties and reactivity. Its applications range from catalysis and chiral auxiliaries to protecting groups and solvents. Understanding its physical and chemical properties, as well as its synthesis and reaction mechanisms, is crucial for its effective use in various synthetic processes. Future research may explore new applications and more efficient synthesis methods for NMCHA.

References

1. Smith, M. B., & March, J. (2007). March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.). Wiley.
2. Carey, F. A., & Sundberg, R. J. (2007). Advanced Organic Chemistry: Part A: Structure and Mechanisms (5th ed.). Springer.
3. Solomons, T. W. G., & Fryhle, C. B. (2008). Organic Chemistry (9th ed.). Wiley.
4. Larock, R. C. (1999). Comprehensive Organic Transformations: A Guide to Functional Group Preparations (2nd ed.). Wiley-VCH.
5. Hanessian, S. (1993). Chirality in Drug Design and Action. Marcel Dekker.
6. Zhang, Y., & Wang, L. (2015). Synthesis and Application of N-Methylcyclohexylamine. Chinese Journal of Organic Chemistry, 35(1), 1-10.
7. National Center for Biotechnology Information (NCBI). PubChem Compound Database; CID=12251.
8. Material Safety Data Sheet (MSDS) for N-Methylcyclohexylamine. Sigma-Aldrich.

This comprehensive review provides a detailed understanding of N-Methylcyclohexylamine, its properties, synthesis, and applications, making it a valuable resource for researchers and practitioners in the field of organic chemistry.