(S)-(-)-2-(Diphenylhydroxymethyl)pyrrolidine
[CAS# 112068-01-6]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Amino alcohol derivative
• Name: (S)-(-)-2-(Diphenylhydroxymethyl)pyrrolidine
• Synonyms: alpha,alpha-Diphenyl-L-prolinol; (S)-(-)-alpha,alpha-Diphenyl-2-pyrrolidinemethanol
• Molecular Formula: C₁₇H₁₉NO
• Molecular Weight: 253.34
• CAS Registry Number: 112068-01-6
• EC Number: 601-153-1
• SMILES: C1C[C@H](NC1)C(C2=CC=CC=C2)(C3=CC=CC=C3)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Melting point: 77 - 80 °C (Expl.)
• Boiling point: 411.3±12.0 °C 760 mmHg (Calc.)^*
• Flash point: 133.3±10.1 °C (Calc.)^*
• Index of refraction: 1.597 (Calc.)^*
• Alpha: -59 ° (c=3, methanol 25 °C) (Expl.)

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

Safety Data

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

Hazard Classification

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

Discovery and Applications

(S)-(-)-2-(Diphenylhydroxymethyl)pyrrolidine, also known as (S)-(-)-α,α-diphenyl-2-pyrrolidinemethanol, is a chiral organic compound with the molecular formula C₁₇H₁₉NO and CAS number 112068-01-6. This compound is characterized by a pyrrolidine ring substituted with a hydroxymethyl group bearing two phenyl rings, and it exhibits significant optical activity, with a specific rotation of [α]₂₀/D −67° in chloroform.

The synthesis of (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine can be achieved through several methods. One common approach involves the reaction of pyrrolidine with diphenylmethanol in the presence of a suitable acid catalyst. This reaction leads to the formation of the desired product with high enantiomeric purity. Another method utilizes the reduction of the corresponding imine intermediate, which can be prepared by the condensation of pyrrolidine with a suitable carbonyl compound. The reduction is typically carried out using borane or other reducing agents to yield the (S)-enantiomer selectively.

In terms of applications, (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine serves as a valuable chiral auxiliary in asymmetric synthesis. Its ability to induce chirality in reactions makes it an essential component in the synthesis of various biologically active molecules. Notably, it has been employed in the synthesis of pharmaceuticals such as salmeterol and dapoxetine hydrochloride, where it plays a crucial role in controlling the stereochemistry of the final products. Additionally, this compound has been utilized in organocatalysis, particularly in reactions involving the formation of carbon-carbon bonds, where its chiral nature enhances the selectivity and efficiency of the processes.

Researchers have also explored the use of (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine in the development of novel catalysts for enantioselective reactions. For instance, when reacted with catecholborane, it forms a spiroborate ester that can catalyze the enantioselective reduction of ketones, leading to the formation of enantiopure alcohols. Similarly, mesoporous silica functionalized with this compound has been shown to catalyze the addition of diethylzinc to benzaldehyde, producing (S)-1-phenylpropanol with high enantiomeric excess.

The compound is commercially available from various chemical suppliers and is typically provided as a white to off-white crystalline powder. It is soluble in chloroform and should be stored in a cool, dry place, protected from light and moisture, to maintain its stability and purity.

In summary, (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine is a versatile chiral building block with significant applications in asymmetric synthesis and organocatalysis. Its role in the synthesis of enantiomerically pure pharmaceuticals underscores its importance in modern medicinal chemistry. Ongoing research continues to explore its potential in developing new catalytic systems and synthetic methodologies, highlighting its value in the advancement of chemical and pharmaceutical sciences.

References

2021. Intramolecular Williamson Etherification of 1,5-Halohydrins. Science of Synthesis.
DOI: SD-137-00107

2013. Asymmetric Organocatalysis and the Nitro Group Functionality. Synthesis.
DOI: 10.1055/s-0033-1338522

2014. Preparation of the Zinc Enolate Equivalent of Amides by Zinciomethylation of Isocyanates: Catalytic Asymmetric Reformatsky-Type Reaction. Synthesis.
DOI: 10.1055/s-0034-1378514