L-prolinamide

Base Information

• Chemical Name: L-prolinamide
• CAS No.: 7531-52-4
• Molecular Formula: C5H10N2O
• Molecular Weight: 114.147
• Hs Code.: 29339900
• European Community (EC) Number: 231-397-0
• UNII: VD6PQK9DHG
• DSSTox Substance ID: DTXSID00226268
• Nikkaji Number: J25.973J
• Wikidata: Q27103084
• Metabolomics Workbench ID: 51285
• ChEMBL ID: CHEMBL1222059
• Mol file: 7531-52-4.mol

Synonyms:2-pyrrolidinecarboxamide;prolinamide;prolinamide, (L)-isomer

Chemical Property of L-prolinamide

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 0.000923mmHg at 25°C
• Melting Point: 97-102 °C
• Refractive Index: 1.4720 (estimate)
• Boiling Point: 303.6 °C at 760 mmHg
• PKA: 16.21±0.20(Predicted)
• Flash Point: 137.4 °C
• PSA: 55.12000
• Density: 1.106 g/cm³
• LogP: 0.25280
• Storage Temp.: -20°C
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• Water Solubility.: Soluble in water and ethanol (50 mg/ml).
• XLogP3: -0.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 114.079312947
• Heavy Atom Count: 8
• Complexity: 103

Purity/Quality:

min98% ^*data from raw suppliers

L-Prolinamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 22-24/25-36/37/39-26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC(NC1)C(=O)N
• Isomeric SMILES: C1C[C@H](NC1)C(=O)N
• Chemical Composition and Structure: L-Prolinamide is an important intermediate compound used in the synthesis of polypeptides and chiral drugs. It is composed of a proline amino acid unit with an amide functional group.
• Mechanism of Action: L-Prolinamide serves as a chiral ligand in asymmetric catalysis reactions, including Robinson cyclization and Aldol reactions. It participates in various organic transformations as a catalyst or co-catalyst, enhancing reaction rates and product yields.
• Uses: L-Prolinamide derivatives have been evaluated as potential organocatalysts for Aldol reactions. It has also been utilized in enzymatic polymerization to generate immobilized L-Prolinamide, which exhibits catalytic activity in Aldol reactions. Additionally, L-Prolinamide is used as a model compound in solubility studies and as a catalyst in the synthesis of γ-nitroketones.; L-Prolinamide has been synthesized in high yields without using complicated chemistry or expensive chemicals, highlighting its importance as a readily available intermediate compound in organic synthesis.
• Production Methods: L-Prolinamide is synthesized from L-proline through a series of chemical reactions, including esterification and ammonolysis. It is produced on an industrial scale using proline as the raw material.
• Analysis Method: Liquid chromatography has been developed as an analytical method for detecting L-Prolinamide and its derivatives. This method allows for accurate and sensitive quantification of L-Prolinamide in various samples.
• General Description: L-Prolinamide is a versatile and efficient organocatalyst, particularly valued for its role in asymmetric aldol reactions, where it enables high enantioselectivity (up to 99% ee) and diastereoselectivity (anti/syn ratios up to 99:1). It is recoverable and reusable with minimal loss in performance over multiple cycles, making it suitable for large-scale industrial applications. Additionally, derivatives of L-prolinamide have been utilized in the rational design of chiral acyl transfer catalysts, such as DMAP-N-oxides, for dynamic kinetic resolution, further demonstrating its broad utility in synthetic chemistry.

Technology Process of L-prolinamide

There total 30 articles about L-prolinamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

Z-Pro-NH2 (34079-31-7,58274-22-9) → L-prolinamide (7531-52-4)

Guidance literature:

With 10% palladium on carbon; hydrogen; In methanol; for 7h;

DOI:10.1016/j.ejmech.2008.12.022

Reference yield: 95.3%

N-acetyl-L-prolinamide (16395-58-7) → L-prolinamide (7531-52-4)

Guidance literature:

With hydrogenchloride; In water; at 103 ℃; for 2h; Temperature;

Reference yield: 91.0%

L-proline methyl ester monohydrochloride (2133-40-6) → L-prolinamide (7531-52-4)

Guidance literature:

With ammonia; In methanol;

upstream raw materials:

methyl (2S)-pyrrolidine carboxylate

ethyl (2S)-pyrrolidine-2-carboxylate

(S)-2-Carbamoyl-pyrrolidine-1-carboxylic acid 2-(4-methoxy-phenyl)-2-oxo-ethyl ester

(S)-tert-butyl 2-carbamoylpyrrolidine-1-carboxylate

Downstream raw materials:

Z-Pro-NH₂

(S)-2-Aminomethylpyrrolidin

Z-D-His(CH₂Ph)-L-Pro-NH₂

Z-L-His(CH₂Ph)-L-Pro-NH₂

Refernces

A highly efficient large-scale asymmetric direct intermolecular aldol reaction employing L-prolinamide as a recoverable catalyst

10.1002/adsc.201000355

The research focuses on the development of a highly efficient, large-scale asymmetric direct intermolecular aldol reaction using l-prolinamide as a recoverable catalyst. The purpose of this study was to create a simple, bifunctional, recoverable, and reusable organocatalyst that promotes aldol reactions with a high level of enantioselectivity. The catalyst was effective with a wide range of aromatic and heteroaromatic aldehydes with cyclic and acyclic ketones, yielding anti-aldol products with up to 99:1 anti/syn ratio and 98% ee. The catalyst could be easily recovered and reused with only a slight decrease in enantioselectivity over five cycles. The study concluded that l-prolinamide 1b is a robust and effective catalyst for highly enantioselective aldol reactions, and its application can be scaled up while maintaining the same level of enantioselectivity, offering significant potential for industrial applications. Key chemicals used in the process include l-prolinamide derivatives as catalysts, 3-methylbenzoic acid as a cocatalyst, and various aldehydes and ketones as substrates.

Simple, inexpensive, and facile l-prolinamide used as a recyclable organocatalyst for highly efficient large-scale asymmetric direct aldol reactions

10.1016/j.tetasy.2011.05.008

The study focuses on the development of a simple, inexpensive, and efficient method for asymmetric direct aldol reactions using L-prolinamide as a recyclable organocatalyst. The main objective was to obtain highly enantiomerically enriched anti-aldol products, which are valuable in industrial applications. A series of prolinamides (compounds 1-10) were synthesized and tested for their catalytic activity in the asymmetric aldol reaction between benzaldehyde and cyclohexanone. The study found that prolinamide 6, in particular, showed high catalytic efficiency with only 5 mol % catalyst loading and 4 equivalents of ketone, yielding aldol products with high diastereoselectivity (up to anti/syn 99:1) and enantioselectivity (up to 99%), and significantly enhanced reaction yield (up to 99%). The catalyst could be easily recovered and reused without a significant decrease in enantioselectivity, making it a promising candidate for large-scale industrial applications. The chemicals used in the study included various prolinamides, benzaldehyde, cyclohexanone, and acetic acid, serving as catalysts, reactants, and a cocatalyst, respectively, to facilitate the aldol reaction and improve its efficiency and selectivity.

Rational Design of 2-Substituted DMAP- N-oxides as Acyl Transfer Catalysts: Dynamic Kinetic Resolution of Azlactones

10.1021/jacs.0c09075

The study presents the rational design and synthesis of novel chiral 2-substituted DMAP-N-oxides, derived from L-prolinamides, for use as acyl transfer catalysts in the dynamic kinetic resolution (DKR) of azlactones. The purpose of these catalysts is to enhance the catalytic activity and utilization of the C2 position of the pyridine ring while avoiding steric hindrance. The researchers used simple methanol (MeOH) as a nucleophile to produce various L-amino acid derivatives with high yields (up to 98%) and enantioselectivities (up to 96% ee). The study also involved the use of benzoic acid to reduce the activation energy by participating in the construction of a hydrogen-bond bridge, which improved the reaction rate. Experiments and DFT calculations revealed that the oxygen atom in the 2-substituted DMAP-N-oxide acted as the nucleophilic site, and the N?H bond functioned as the H-bond donor, with high enantioselectivity governed by steric factors. This work paves the way for the development of chiral 2-substituted DMAP-N-oxides as efficient acyl transfer catalysts.