(S)-(+)-2,2-Dimethylcyclopropanecarboxamide
[CAS# 75885-58-4]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: (S)-(+)-2,2-Dimethylcyclopropanecarboxamide
• Synonyms: (1S)-2,2-dimethylcyclopropane-1-carboxamide
• Molecular Formula: C₆H₁₁NO
• Molecular Weight: 113.16
• CAS Registry Number: 75885-58-4
• EC Number: 278-334-3
• SMILES: CC1(C[C@@H]1C(=O)N)C

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Melting point: 135 - 137 ºC (Expl.)
• Boiling point: 225.1±7.0 ºC 760 mmHg (Calc.)^*
• Flash point: 89.9±18.2 ºC (Calc.)^*
• Index of refraction: 1.48 (Calc.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

(S)-(+)-2,2-Dimethylcyclopropanecarboxamide is a chiral, alicyclic amide characterized by a three-membered cyclopropane ring bearing two methyl groups at the 2-position and a carboxamide (-CONH₂) functional group at the 1-position. The presence of a stereocenter in the molecule imparts optical activity, and the compound exists specifically as the (S)-(+)-enantiomer, indicating that it rotates plane-polarized light in a dextrorotatory manner. The compact and strained cyclopropane ring makes this compound structurally interesting and chemically significant, especially in asymmetric synthesis and medicinal chemistry.

The exploration of cyclopropane derivatives began in the early 20th century, driven by interest in the reactivity of small-ring systems and their utility in organic synthesis. Cyclopropanes are notable for their ring strain and unique electronic properties, which influence their behavior in chemical reactions. In particular, substituted cyclopropanes with defined stereochemistry, such as (S)-(+)-2,2-dimethylcyclopropanecarboxamide, have been employed as chiral building blocks and intermediates in the synthesis of more complex organic molecules.

The carboxamide functional group contributes significant hydrogen bonding ability and chemical stability, enhancing the compound’s solubility and compatibility with both hydrophilic and hydrophobic reagents. In the (S)-(+)-enantiomer, the spatial orientation of the carboxamide relative to the cyclopropane ring is defined, allowing for specific and predictable interactions with chiral environments, such as enzyme active sites or asymmetric catalysts.

Applications of (S)-(+)-2,2-dimethylcyclopropanecarboxamide span both academic and industrial domains. One key use is as a chiral auxiliary or chiral source in asymmetric synthesis. The rigid, three-membered ring helps to transfer chirality to other parts of a target molecule during chemical transformations. It can influence stereochemical outcomes in reactions such as nucleophilic additions, reductions, and rearrangements, which are crucial for producing optically active pharmaceuticals or agrochemicals.

In medicinal chemistry, substituted cyclopropane derivatives are of significant interest due to their ability to mimic transition states, improve metabolic stability, and modulate biological activity. The inclusion of a cyclopropane ring often leads to enhanced receptor binding or bioavailability in drug candidates. The (S)-(+)-2,2-dimethylcyclopropanecarboxamide structure, while not a widely marketed drug itself, represents a core scaffold that can be modified to produce bioactive compounds, including enzyme inhibitors, receptor ligands, and peptidomimetics.

Synthetic methods for producing this compound typically involve stereoselective cyclopropanation reactions. A common route is through the use of diazo compounds and alkenes in the presence of chiral catalysts, which can induce the formation of a specific enantiomer. Alternatively, chiral auxiliaries or reagents may be used to control the stereochemical outcome during the formation of the cyclopropane ring or subsequent introduction of the amide group.

As a chiral compound, (S)-(+)-2,2-dimethylcyclopropanecarboxamide must be handled with attention to enantiomeric purity, especially when intended for use in stereosensitive applications such as drug synthesis or biological studies. Enantiomeric excess can be determined by chiral HPLC, optical rotation measurements, or NMR spectroscopy with chiral shift reagents.

The overall utility of (S)-(+)-2,2-dimethylcyclopropanecarboxamide arises from its combination of a strained, reactive ring system and a hydrogen-bonding amide moiety, along with its defined chirality. These features make it a valuable compound in the toolkit of synthetic and medicinal chemists seeking to construct complex, enantioselective architectures. It continues to be employed in developing stereoselective methodologies and exploring structure-activity relationships in bioactive compound libraries.

References

2003. Cilastatin. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-03-0155

2007. A simple method to determine concentration of enantiomers in enzyme-catalyzed kinetic resolution. Biotechnology Letters, 29(7).
DOI: 10.1007/s10529-007-9358-x

2024. Recombinant Amidases: Recent Insights and its Applications in the Production of Industrially Important Fine Chemicals. Molecular Biotechnology, 66(11).
DOI: 10.1007/s12033-024-01123-8