A literature survey via Reaxys revealed 2 references in which this compound was described as the product. The first synthesis has been published by Corey in the Journal of Organic Chemistry in 1988: N-(benzyloxycarbonyl)-(S)-proline (3) was synthesized in 75.2% yield from proline by reaction with benzyl chloroformate in an aqueous solution at 0–5°C. E. J. Corey, J. Org. Chem., Vol. 53, No. 12, 1988, 2861-2863 seemed to be the best choice for its high yield.
The protection of proline with benzylchloroformate gave a colourless solid, which recrystallized from petrolium ether. The yield of 75.2% is below that reportedin the literature (96%). The purity of the product could not be proofed, since no enough analytic data are available. For the product (3) no GC-MS was recorded, because of its carbon acid group that might damage the mass spectrometry system.
The hydroxide ion of NaOH deprotonates the NH-group of proline to form water and the electron pair of the nitrogen anion undergo a nucleophilic attack to the carbon atom of the carbonyl-group to give (3). The sodium cation forms with chloride anion sodiumchloride that prcipitates. An example for the application of the cyclic amino acid is its use as a pharmaceutical intermidiate, which is used for the synthesis of Eletriptan, a drug for the treatment of migriane.
Table of Contents
1 Results and discussion
1.1 Synthesis of N-(benzyloxycarbonyl)-(S)-proline (3)[1]
1.2 Synthesis of N-(benzyloxycarbonyl)-(S)-proline Methyl Ester (5)[1]
1.3 Synthesis of 2-amino-3-methylbutanol (Valinol) (7)[3]
1.4 Synthesis of (S)-4-isopropyl-2-oxazolidinone (10)[7]
1.5 Synthesis of di-tert-butyl 1-(2,6-diisopropylphenyl)-hydrazine-1,2-dicarboxylate (11)[9]
1.6 Synthesis of 2-(2,6-diisopropyl-phenyl)hydrazin-1-ium chloride (12)[9]
1.7 Synthesis of dimethyl o-tolylboronate (14)[10]
1.8 Synthesis of 1-methyl-4'-methoxybiphenyl (16)[11]
1.9 Synthesis of 2-iodobenzoic acid (18)[13]
1.10 Synthesis of 1,1,2,2-tetraphenylethylen (20)[14]
1.11 Synthesis of 5-hydroxy-3-oxo-5-phenylpentanoic acid methyl ester (23)[16]
2 Experimental Section
2.1 General Procedures
2.1.1 Working method with air and moisture sensitive chemicals
2.1.2 Solvents
2.1.3 Chromatographic methods
2.1.4 Analytical methods
2.1.5 Miscellaneous information
2.2 Synthesis of N-(benzyloxycarbonyl)-(S)-proline (3)[1]
2.3 Synthesis of N-(benzyloxycarbonyl)-(S)-proline methyl ester (5)[1]
2.4 Synthesis of 2-amino-3-methylbutanol (Valinol) (7)[3]
2.5 Synthesis of (S)-4-isopropyl-2-oxazolidinone (10)[7]
2.6 Synthesis of di-tert-butyl 1-(2,6-diisopropylphenyl)-hydrazine-1,2-dicarboxylate (11)[9]
2.7 Synthesis of 2-(2,6-diisopropyl-phenyl)hydrazin-1-ium chloride (12)[9]
2.8 Synthesis of dimethyl o-tolylboronate (14)[10]
2.9 Synthesis of 1-methyl-4'-methoxybiphenyl (16)[11]
2.10 Synthesis of 2-iodobenzoic acid (18)[13]
2.11 Synthesis of 1,1,2,2-tetraphenylethylen (20)[14]
2.12 Synthesis of 5-hydroxy-3-oxo-5-phenylpentanoic acid methyl ester (23)[16]
Objectives & Research Topics
This experimental module aims to detail the laboratory synthesis of various organic chemical compounds, documenting reaction conditions, yields, and analytical verification methods used to confirm the identity and purity of the products.
- Methodologies for the protection and esterification of amino acids.
- Reductive synthesis techniques for amino alcohols.
- Organometallic reaction protocols, including Grignard and Suzuki coupling reactions.
- Advanced chemical synthesis, such as the McMurry reaction for alkene formation.
- Experimental validation through GC-MS, NMR, and IR spectroscopy.
Extract from the Book
1.1 Synthesis of N-(benzyloxycarbonyl)-(S)-proline (3)[1]
A literature survey via Reaxys revealed 2 references in which this compound was described as the product. The first synthesis has been published by Corey in the Journal of Organic Chemistry in 1988: N-(benzyloxycarbonyl)-(S)-proline (3) was synthesized in 75.2 % yield from proline by reaction with benzyl chloroformate in an aqueous solution at 0 – 5°C. E. J. Corey, J. Org. Chem., Vol. 53, No. 12, 1988, 2861-2863 seemed to be the best choice for its high yield.
The protection of proline with benzylchloroformate gave a colourless solid, which recrystallized from petrolium ether. The yield of 75.2 % is below that reportedin the literature (96 %)[1]. The purity of the product could not be proofed, since no enough analytic data are available. For the product (3) no GC-MS was recorded, because of its carbon acid group that might damage the mass spectrometry system.
The hydroxide ion of NaOH deprotonates the NH-group of proline to form water and the electron pair of the nitrogen anion undergo a nucleophilic attack to the carbon atom of the carbonyl-group to give (3). The sodium cation forms with chloride anion sodiumchloride that prcipitates (see scheme 2).
An example for the application of the cyclic amino acid is its use as a pharmaceutical intermidiate, which is used for the synthesis of Eletriptan, a drug for the treatment of migriane.[10]
Summary of Chapters
1 Results and discussion: Provides an overview of literature-based synthesis methods for several chemical compounds, comparing experimental results like yield and purity against reported data.
2 Experimental Section: Details the specific laboratory procedures, materials, and analytical methods used for the synthesis and characterization of the chemical compounds discussed.
Keywords
Organic Synthesis, Chemical Compounds, Reaction Mechanism, Proline, Valinol, Grignard Reaction, Suzuki Coupling, McMurry Reaction, Spectroscopic Analysis, GC-MS, Yield, Purification, Chemical Laboratory, Reagents, Catalyst.
Frequently Asked Questions
What is the primary focus of this work?
The document serves as an experimental report focused on the practical synthesis of various specialized chemical compounds, including amino acid derivatives and organometallic products.
What central thematic fields are addressed?
The work covers synthetic organic chemistry, specifically focusing on protection strategies, reduction reactions, and C-C bond formation processes.
What is the core objective of the research?
The objective is to perform and optimize the synthesis of target compounds while comparing achieved experimental yields and analytical data with previously established literature.
Which scientific methods are primarily utilized?
The study utilizes standard organic laboratory techniques such as Schlenk line procedures, reflux synthesis, column chromatography, and analytical verification via GC-MS, NMR, and IR spectroscopy.
What does the experimental part encompass?
The experimental section describes the specific reagents, apparatus (such as melting point devices and mass spectrometers), and precise environmental conditions required for each synthesis.
Which keywords characterize the work?
Key terms include Organic Synthesis, Suzuki Coupling, Grignard Reaction, Proline derivatives, and Spectroscopic Analysis.
How is the synthesis of (S)-4-isopropyl-2-oxazolidinone achieved?
It is synthesized via the oxidative cyclocarbonylation of L-valinol with diethylcarbonate in the presence of potassium carbonate at 130 °C.
What is the significance of the palladium-catalyzed synthesis in this work?
The work demonstrates the use of a Suzuki coupling between dimethyl-o-tolylboronate and 1-iodo-4-methoxybenzene to synthesize 1-methyl-4'-methoxybiphenyl, highlighting the catalytic mechanism and the role of palladium in cross-coupling.
- Citation du texte
- Sadik Mejid (Auteur), 2015, Synthesis of Chemical Compounds. Results, Discussion and Experimental Section, Munich, GRIN Verlag, https://www.grin.com/document/475233
