This document provides information about several synthetic reagents and their applications:
- Aluminum isopropoxide is used in reductions and oxidations. Diazomethane methylates carboxylic acids and forms cyclopropanes from alkenes. Osmium tetroxide dihydroxylates alkenes and stains polymers. Triphenylphosphine is used in Mitsunobu, Appel, and Staudinger reactions. N-Bromosuccinimide brominates alkenes, allylic/benzylic positions, and carbonyls. Diazopropane and diethyl azodicarboxylate form cyclopropanes and assist Mitsunobu reactions.
This document discusses several reagents used in organic synthesis:
1) Wittig reagent is used to synthesize alkenes from ketones and aldehydes via the Wittig reaction. It is prepared from triphenylphosphine and alkyl halides.
2) Diazopropane is used for cyclopropanation of alkenes and is prepared by oxidation of acetohydrazone.
3) BOP reagent is commonly used for peptide coupling and esterification due to its ability to form reactive hydroxybenzotriazolyl intermediates. It involves generation of a carboxylate anion which attacks the phosphorus center.
The Pinner pyrimidine synthesis involves the condensation of 1,3-dicarbonyl compounds with amidines catalyzed by acids or bases to form pyrimidine derivatives. Specifically, it describes the reaction of amidine derivatives with β-keto esters, malonic esters, or β-diketones to produce various substituted pyrimidines. Examples are provided of important pyrimidine drugs synthesized using this method, such as sulfamerazine and trimethoprim.
This document summarizes several organic reactions used in heterocyclic chemistry. It describes the Debus–Radziszewski reaction for imidazole synthesis, the Knorr reaction for pyrrole synthesis, the Pinner reaction for pyrimidine synthesis, the Combes reaction for quinoline synthesis, the Bernthsen reaction for acridine synthesis, the Smiles rearrangement, and the Traube reaction for purine synthesis. For each reaction, it provides the starting materials, product, mechanism, and some applications. The document is intended to present an overview of important heterocyclic reactions for students of pharmaceutical chemistry.
Synthetic Reagent and Its Applications (M. Pharm)MohdShafeeque4
The document summarizes various synthetic reagents and their applications. It describes 12 reagents including aluminium isopropoxide, N-bromosuccinimide, diazomethane, dicyclohexylcarbodiimide, Wilkinson reagent, Wittig reagent, osmium tetroxide, titanium chloride, diazopropane, diethyl azodicarboxylate, triphenylphosphine, and BOP reagent. For each reagent, it provides information on chemical formula, structure, preparation method, and typical applications. The document serves as a useful reference for organic chemistry students and researchers.
This document summarizes the Pinner pyrimidine synthesis reaction. The reaction involves the condensation of a non-N-substituted amidine and β-keto ester (β-diketone) in the presence of an acid catalyst to form a pyrimidine heterocyclic ring. The mechanism proceeds through protonation, nucleophilic attack, dehydration, and deprotonation steps. Pyrimidine derivatives synthesized via this reaction are used in drugs to treat conditions like malaria, viruses, and cancer.
Wilkinson's catalyst, also known as chloridotris(triphenylphosphane)rhodium(I), is a coordination complex of rhodium with the formula RhCl(PPh3)3. It is a red-brown solid that is soluble in hydrocarbon solvents and used widely as a catalyst for hydrogenation of alkenes. Wilkinson's catalyst is obtained by treating rhodium(III) chloride hydrate with excess triphenylphosphine, which acts as a reducing agent to reduce rhodium from Rh(III) to Rh(I). It adopts a slightly distorted square planar structure and undergoes fast dynamic exchange processes in solution.
Synthetic Reagents & Applications in Organic ChemistryAjay Kumar
This document discusses 12 synthetic reagents and their applications in organic chemistry. It describes the preparation, structure, and common uses of each reagent which include aluminium isopropoxide, N-bromosuccinimide, diazomethane, dicyclohexyl-carbodimide, Wilkinson reagent, Wittig reagent, osmium tetroxide, titanium chloride, diazopropane, diethyl azodicarboxylate, triphenylphosphine, and benzotriazol-1-yloxy)tris(dimethyl-amino)phosphonium hexafluorophosphate. These reagents are used for transformations like oxidation, reduction, bromination,
The document summarizes the Brook rearrangement reaction. It was discovered in 1957 by Adrian Brook and involves the migration of a silyl group from carbon to oxygen under basic conditions. The mechanism proceeds through the formation of a pentavalent silicon intermediate. The rearrangement has various applications in synthesis, such as constructing 8-membered rings and chiral silyl ethers. It has been used to synthesize compounds like gamma-amino-beta-hydroxy amides and alpha-hydroxy acid derivatives.
This document discusses several reagents used in organic synthesis:
1) Wittig reagent is used to synthesize alkenes from ketones and aldehydes via the Wittig reaction. It is prepared from triphenylphosphine and alkyl halides.
2) Diazopropane is used for cyclopropanation of alkenes and is prepared by oxidation of acetohydrazone.
3) BOP reagent is commonly used for peptide coupling and esterification due to its ability to form reactive hydroxybenzotriazolyl intermediates. It involves generation of a carboxylate anion which attacks the phosphorus center.
The Pinner pyrimidine synthesis involves the condensation of 1,3-dicarbonyl compounds with amidines catalyzed by acids or bases to form pyrimidine derivatives. Specifically, it describes the reaction of amidine derivatives with β-keto esters, malonic esters, or β-diketones to produce various substituted pyrimidines. Examples are provided of important pyrimidine drugs synthesized using this method, such as sulfamerazine and trimethoprim.
This document summarizes several organic reactions used in heterocyclic chemistry. It describes the Debus–Radziszewski reaction for imidazole synthesis, the Knorr reaction for pyrrole synthesis, the Pinner reaction for pyrimidine synthesis, the Combes reaction for quinoline synthesis, the Bernthsen reaction for acridine synthesis, the Smiles rearrangement, and the Traube reaction for purine synthesis. For each reaction, it provides the starting materials, product, mechanism, and some applications. The document is intended to present an overview of important heterocyclic reactions for students of pharmaceutical chemistry.
Synthetic Reagent and Its Applications (M. Pharm)MohdShafeeque4
The document summarizes various synthetic reagents and their applications. It describes 12 reagents including aluminium isopropoxide, N-bromosuccinimide, diazomethane, dicyclohexylcarbodiimide, Wilkinson reagent, Wittig reagent, osmium tetroxide, titanium chloride, diazopropane, diethyl azodicarboxylate, triphenylphosphine, and BOP reagent. For each reagent, it provides information on chemical formula, structure, preparation method, and typical applications. The document serves as a useful reference for organic chemistry students and researchers.
This document summarizes the Pinner pyrimidine synthesis reaction. The reaction involves the condensation of a non-N-substituted amidine and β-keto ester (β-diketone) in the presence of an acid catalyst to form a pyrimidine heterocyclic ring. The mechanism proceeds through protonation, nucleophilic attack, dehydration, and deprotonation steps. Pyrimidine derivatives synthesized via this reaction are used in drugs to treat conditions like malaria, viruses, and cancer.
Wilkinson's catalyst, also known as chloridotris(triphenylphosphane)rhodium(I), is a coordination complex of rhodium with the formula RhCl(PPh3)3. It is a red-brown solid that is soluble in hydrocarbon solvents and used widely as a catalyst for hydrogenation of alkenes. Wilkinson's catalyst is obtained by treating rhodium(III) chloride hydrate with excess triphenylphosphine, which acts as a reducing agent to reduce rhodium from Rh(III) to Rh(I). It adopts a slightly distorted square planar structure and undergoes fast dynamic exchange processes in solution.
Synthetic Reagents & Applications in Organic ChemistryAjay Kumar
This document discusses 12 synthetic reagents and their applications in organic chemistry. It describes the preparation, structure, and common uses of each reagent which include aluminium isopropoxide, N-bromosuccinimide, diazomethane, dicyclohexyl-carbodimide, Wilkinson reagent, Wittig reagent, osmium tetroxide, titanium chloride, diazopropane, diethyl azodicarboxylate, triphenylphosphine, and benzotriazol-1-yloxy)tris(dimethyl-amino)phosphonium hexafluorophosphate. These reagents are used for transformations like oxidation, reduction, bromination,
The document summarizes the Brook rearrangement reaction. It was discovered in 1957 by Adrian Brook and involves the migration of a silyl group from carbon to oxygen under basic conditions. The mechanism proceeds through the formation of a pentavalent silicon intermediate. The rearrangement has various applications in synthesis, such as constructing 8-membered rings and chiral silyl ethers. It has been used to synthesize compounds like gamma-amino-beta-hydroxy amides and alpha-hydroxy acid derivatives.
This document discusses strategies for synthesizing three, four, five, and six-membered heterocyclic rings. It outlines three strategies for each ring size, including the Gabriel ring closure and Hassner synthesis for aziridines, pyrolysis of cyclopropyl azides and photocycloaddition for azetines, the Paal-Knorr and Hantzsch syntheses for pyrroles, and the Hantzsch synthesis and reactions with maleic anhydride for pyridines and pyridazines. A variety of heterocyclic compounds are derived from carbocyclic precursors by replacing carbon atoms with heteroatoms like nitrogen, oxygen, or sulfur.
THE BERNTHSEN ACRIDINE SYNTHESIS IS THE SYNTHESIS OF ACRIDINE FIRSTLY PERFORMED BY BERNTHSEN THEREFORE KNOWN AS BERNTHSEN ACRIDINE SYNTHESIS. THIS PRESENTATION INCLUDES THE SYNTHESIS WITH ITS MECHANISM AND APPLICATION AS ASKED IN EXAMS.
This document discusses several synthetic reagents and their applications. It introduces aluminum isopropoxide, N-bromosuccinamide, diazomethane, dicyclohexylcarbodiimide, Wilkinson reagent, and Wittig reagent. For each reagent, it provides information on preparation, reaction mechanisms, and common uses. The document aims to describe important reagents used in organic synthesis and their roles in producing natural products, pharmaceuticals, and industrial chemicals.
It is an intramolecular rearrangement reaction in which the 1,2-migration of silyl group from carbon to oxygen under basic conditions.It involves the formation of a pentacoordinate siliconintermediate.Discovered by Adrian Gibbs Brook in 1958.
Mitsunubu reaction had been synthesised by Japanese scientist OYO Mitsunbu.
It involves the Conversion of primary, Secondary alcohol into the ester group.
It follows SN2 mechanism.
The document discusses key concepts regarding enantiomers including:
1. Enantiomers are chiral molecules that are non-superimposable mirror images of one another that rotate plane-polarized light in opposite directions.
2. Diastereomers have more than one asymmetric carbon center and are physically different.
3. Differences in interactions between enantiomers and biological systems can lead to differences in pharmacological effects.
4. Stereoselectivity can occur during the absorption, distribution, metabolism, and excretion of chiral drugs due to interactions with transporters, proteins, and enzymes.
5. Case studies provide specific examples of how stereoselectivity influences the pharmacokinetics of drug enantiomers
This document discusses Traube purine synthesis and several purine derivatives including mercaptopurine, theophylline, and thioguanine. It provides information on:
- Traube first introduced purine synthesis in 1900 involving introduction of a one carbon fragment to bridge nitrogen atoms in pyrimidine rings.
- Mercaptopurine is used to treat cancers and autoimmune diseases but has side effects like bone marrow suppression and increased cancer risk.
- Theophylline is found in tea and used for respiratory issues like asthma as it relaxes bronchial muscles and stimulates the respiratory center.
- Thioguanine is used for certain cancers and inflammatory bowel disease.
The Knorr pyrazole synthesis converts a hydrazine or its derivatives and a 1,3-dicarbonyl compound to a pyrazole using an acid catalyst. The mechanism involves an acid-catalyzed imine formation where the hydrazine attacks either carbonyl carbon, followed by attack of the other nitrogen on the other carbonyl group. This diimine compound then deprotonates to form the pyrazole product. The reaction is used to synthesize compounds such as metal chelates, photographic dyes, herbicides, and biologically active molecules.
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDEShikha Popali
SYNTHETIC REAGENTS AND APPLICATIONS OF ALUMINIUM ISOPROPOXIDE ITS ALTERNATIVE NAMES AND ITS PHYSICAL PROPERTIRS , HANDLING, STORAGE, PRECAUTIONS, PREPARATIONS, SYNTHETIC APPLICATIONS
The Ullmann reaction involves the condensation of aryl halides in the presence of finely divided copper or copper bronze at an elevated temperature to form diaryl derivatives. Two proposed mechanisms are the free radical mechanism, where copper generates an aryl radical, and the ionic mechanism, where an organocuprate intermediate is formed. The Ullmann reaction is useful for synthesizing biaryls, polyaryls, diaryl amines, diaryl ethers, and gossypol.
The document discusses the Knorr pyrazole synthesis reaction which converts hydrazines or derivatives and 1,3-dicarbonyl compounds to pyrazoles using an acid catalyst. The mechanism involves acid-catalyzed imine formation on either carbonyl carbon, followed by attack of the other nitrogen on the other carbonyl group. This forms a diimine compound which deprotonates to generate the final pyrazole product. Several examples of pyrazoles synthesized using this reaction are mentioned, including antipyrine, celecoxib, and metamizole sodium which have various medical applications.
The document describes the synthesis of several drugs including ketoconazole, metronidazole, miconazole, celecoxib, metamizole sodium, terconazole, alprazolam, triamtrene, sulfamerazine, trimethoprim, hydroxychloroquine, quinine, chloroquine, quinacrine, amsacrine, prochlorperazine, promazine, chlorpromazine, and theophylline. The syntheses involve multiple reaction steps starting with various reagents and intermediates to ultimately form the target drug molecule through condensation, reduction, oxidation, hydrolysis, and other organic reactions.
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
The document summarizes the Suzuki and Shapiro reactions. The Suzuki reaction involves a palladium-catalyzed cross-coupling between organoboron compounds and organic halides to form carbon-carbon bonds. It proceeds through oxidative addition, transmetallation, and reductive elimination steps. The Shapiro reaction involves the base-catalyzed decomposition of tosyl hydrazones to form olefins. Both reactions have been used in the synthesis of various drugs and natural products.
Heterocyclic Organic Reaction - By Vishal DakhaleVishalDakhale
This document discusses three heterocyclic organic reactions: the Debus-Radziszewski imidazole synthesis, the Knorr pyrazole synthesis, and the Combes quinoline synthesis. The Debus-Radziszewski reaction synthesizes imidazoles from a dicarbonyl, aldehyde, and ammonia. The Knorr reaction synthesizes pyrazoles from hydrazines and 1,3-dicarbonyl compounds using an acid catalyst. The Combes reaction synthesizes quinolines by condensing unsubstituted anilines with β-diketones followed by an acid-catalyzed ring closure.
The document summarizes Wittig reagent, which is also known as triphenyl phosphoniumylide or alkylidenephosphorane. It forms when triphenyl phosphine reacts with an alkyl halide via an SN2 reaction followed by deprotonation. Wittig reagent is used to incorporate exocyclic methylene groups and synthesize indoles, alpha,beta-unsaturated esters, dienes, olefins, aldehydes, and natural compounds like squalene and beta-carotene. It has various applications in organic synthesis due to its ability to generate carbon-carbon double bonds.
Asymmetric synthesis (As per new syllabus of PCI)
Methods of asymmetric synthesis using chiral pool
Chiral auxiliaries and catalytic asymmetric synthesis
Enantiopure seperation
Stereoselective synthesis
Recent advances
References
The document discusses several important synthetic reagents and their applications, including:
1) Aluminium isopropoxide, which is used as a reducing agent in reductions like the Meerwein-Ponndorf reduction.
2) N-bromosuccinamide, which acts as a brominating and oxidizing agent in reactions like the conversion of monoenes to dienes.
3) Diazomethane, a useful methylating agent that is prepared by the alkaline hydrolysis of bis-(N-nitroso-N-methyl) terephthalimide. It is used in reactions like the synthesis of heterocyclic compounds.
4) Dicyclohexy
This document summarizes the recent progress of using ammonium chloride as a catalyst in organic synthesis. It discusses various reactions where ammonium chloride has been used as a catalyst, including Claisen rearrangement, Ullmann coupling, thia-Michael addition, multi-component reactions to synthesize compounds such as dihydropyrimidinones, imidazo[1,2-a]pyridines, tetrahydrobenzo[a]xanthene-11-ones, and dipeptides. Ammonium chloride allows these reactions to proceed under mild conditions in a selective and environmentally friendly manner. It is an inexpensive, commercially available catalyst that can catalyze reactions under neutral conditions.
This document discusses strategies for synthesizing three, four, five, and six-membered heterocyclic rings. It outlines three strategies for each ring size, including the Gabriel ring closure and Hassner synthesis for aziridines, pyrolysis of cyclopropyl azides and photocycloaddition for azetines, the Paal-Knorr and Hantzsch syntheses for pyrroles, and the Hantzsch synthesis and reactions with maleic anhydride for pyridines and pyridazines. A variety of heterocyclic compounds are derived from carbocyclic precursors by replacing carbon atoms with heteroatoms like nitrogen, oxygen, or sulfur.
THE BERNTHSEN ACRIDINE SYNTHESIS IS THE SYNTHESIS OF ACRIDINE FIRSTLY PERFORMED BY BERNTHSEN THEREFORE KNOWN AS BERNTHSEN ACRIDINE SYNTHESIS. THIS PRESENTATION INCLUDES THE SYNTHESIS WITH ITS MECHANISM AND APPLICATION AS ASKED IN EXAMS.
This document discusses several synthetic reagents and their applications. It introduces aluminum isopropoxide, N-bromosuccinamide, diazomethane, dicyclohexylcarbodiimide, Wilkinson reagent, and Wittig reagent. For each reagent, it provides information on preparation, reaction mechanisms, and common uses. The document aims to describe important reagents used in organic synthesis and their roles in producing natural products, pharmaceuticals, and industrial chemicals.
It is an intramolecular rearrangement reaction in which the 1,2-migration of silyl group from carbon to oxygen under basic conditions.It involves the formation of a pentacoordinate siliconintermediate.Discovered by Adrian Gibbs Brook in 1958.
Mitsunubu reaction had been synthesised by Japanese scientist OYO Mitsunbu.
It involves the Conversion of primary, Secondary alcohol into the ester group.
It follows SN2 mechanism.
The document discusses key concepts regarding enantiomers including:
1. Enantiomers are chiral molecules that are non-superimposable mirror images of one another that rotate plane-polarized light in opposite directions.
2. Diastereomers have more than one asymmetric carbon center and are physically different.
3. Differences in interactions between enantiomers and biological systems can lead to differences in pharmacological effects.
4. Stereoselectivity can occur during the absorption, distribution, metabolism, and excretion of chiral drugs due to interactions with transporters, proteins, and enzymes.
5. Case studies provide specific examples of how stereoselectivity influences the pharmacokinetics of drug enantiomers
This document discusses Traube purine synthesis and several purine derivatives including mercaptopurine, theophylline, and thioguanine. It provides information on:
- Traube first introduced purine synthesis in 1900 involving introduction of a one carbon fragment to bridge nitrogen atoms in pyrimidine rings.
- Mercaptopurine is used to treat cancers and autoimmune diseases but has side effects like bone marrow suppression and increased cancer risk.
- Theophylline is found in tea and used for respiratory issues like asthma as it relaxes bronchial muscles and stimulates the respiratory center.
- Thioguanine is used for certain cancers and inflammatory bowel disease.
The Knorr pyrazole synthesis converts a hydrazine or its derivatives and a 1,3-dicarbonyl compound to a pyrazole using an acid catalyst. The mechanism involves an acid-catalyzed imine formation where the hydrazine attacks either carbonyl carbon, followed by attack of the other nitrogen on the other carbonyl group. This diimine compound then deprotonates to form the pyrazole product. The reaction is used to synthesize compounds such as metal chelates, photographic dyes, herbicides, and biologically active molecules.
Synthetic reagent and applications OF ALUMINIUM ISOPROPOXIDEShikha Popali
SYNTHETIC REAGENTS AND APPLICATIONS OF ALUMINIUM ISOPROPOXIDE ITS ALTERNATIVE NAMES AND ITS PHYSICAL PROPERTIRS , HANDLING, STORAGE, PRECAUTIONS, PREPARATIONS, SYNTHETIC APPLICATIONS
The Ullmann reaction involves the condensation of aryl halides in the presence of finely divided copper or copper bronze at an elevated temperature to form diaryl derivatives. Two proposed mechanisms are the free radical mechanism, where copper generates an aryl radical, and the ionic mechanism, where an organocuprate intermediate is formed. The Ullmann reaction is useful for synthesizing biaryls, polyaryls, diaryl amines, diaryl ethers, and gossypol.
The document discusses the Knorr pyrazole synthesis reaction which converts hydrazines or derivatives and 1,3-dicarbonyl compounds to pyrazoles using an acid catalyst. The mechanism involves acid-catalyzed imine formation on either carbonyl carbon, followed by attack of the other nitrogen on the other carbonyl group. This forms a diimine compound which deprotonates to generate the final pyrazole product. Several examples of pyrazoles synthesized using this reaction are mentioned, including antipyrine, celecoxib, and metamizole sodium which have various medical applications.
The document describes the synthesis of several drugs including ketoconazole, metronidazole, miconazole, celecoxib, metamizole sodium, terconazole, alprazolam, triamtrene, sulfamerazine, trimethoprim, hydroxychloroquine, quinine, chloroquine, quinacrine, amsacrine, prochlorperazine, promazine, chlorpromazine, and theophylline. The syntheses involve multiple reaction steps starting with various reagents and intermediates to ultimately form the target drug molecule through condensation, reduction, oxidation, hydrolysis, and other organic reactions.
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
The document summarizes the Suzuki and Shapiro reactions. The Suzuki reaction involves a palladium-catalyzed cross-coupling between organoboron compounds and organic halides to form carbon-carbon bonds. It proceeds through oxidative addition, transmetallation, and reductive elimination steps. The Shapiro reaction involves the base-catalyzed decomposition of tosyl hydrazones to form olefins. Both reactions have been used in the synthesis of various drugs and natural products.
Heterocyclic Organic Reaction - By Vishal DakhaleVishalDakhale
This document discusses three heterocyclic organic reactions: the Debus-Radziszewski imidazole synthesis, the Knorr pyrazole synthesis, and the Combes quinoline synthesis. The Debus-Radziszewski reaction synthesizes imidazoles from a dicarbonyl, aldehyde, and ammonia. The Knorr reaction synthesizes pyrazoles from hydrazines and 1,3-dicarbonyl compounds using an acid catalyst. The Combes reaction synthesizes quinolines by condensing unsubstituted anilines with β-diketones followed by an acid-catalyzed ring closure.
The document summarizes Wittig reagent, which is also known as triphenyl phosphoniumylide or alkylidenephosphorane. It forms when triphenyl phosphine reacts with an alkyl halide via an SN2 reaction followed by deprotonation. Wittig reagent is used to incorporate exocyclic methylene groups and synthesize indoles, alpha,beta-unsaturated esters, dienes, olefins, aldehydes, and natural compounds like squalene and beta-carotene. It has various applications in organic synthesis due to its ability to generate carbon-carbon double bonds.
Asymmetric synthesis (As per new syllabus of PCI)
Methods of asymmetric synthesis using chiral pool
Chiral auxiliaries and catalytic asymmetric synthesis
Enantiopure seperation
Stereoselective synthesis
Recent advances
References
The document discusses several important synthetic reagents and their applications, including:
1) Aluminium isopropoxide, which is used as a reducing agent in reductions like the Meerwein-Ponndorf reduction.
2) N-bromosuccinamide, which acts as a brominating and oxidizing agent in reactions like the conversion of monoenes to dienes.
3) Diazomethane, a useful methylating agent that is prepared by the alkaline hydrolysis of bis-(N-nitroso-N-methyl) terephthalimide. It is used in reactions like the synthesis of heterocyclic compounds.
4) Dicyclohexy
This document summarizes the recent progress of using ammonium chloride as a catalyst in organic synthesis. It discusses various reactions where ammonium chloride has been used as a catalyst, including Claisen rearrangement, Ullmann coupling, thia-Michael addition, multi-component reactions to synthesize compounds such as dihydropyrimidinones, imidazo[1,2-a]pyridines, tetrahydrobenzo[a]xanthene-11-ones, and dipeptides. Ammonium chloride allows these reactions to proceed under mild conditions in a selective and environmentally friendly manner. It is an inexpensive, commercially available catalyst that can catalyze reactions under neutral conditions.
This document summarizes recent progress in using ammonium chloride as a catalyst in organic synthesis. It describes several reactions where ammonium chloride has been used successfully as a catalyst, including Claisen rearrangement, Ullmann coupling, thia-Michael addition, and multi-component reactions to synthesize compounds such as dihydropyrimidinones, imidazo[1,2-a]pyridines, and tetrahydrobenzo[a]xanthene-11-ones. Ammonium chloride is highlighted as an inexpensive, environmentally friendly catalyst that allows mild and selective transformations under neutral conditions.
Imidazole Derivatives Biological Activity And Synthetic ApproachesBalmukund Thakkar
This document summarizes biological activity and synthetic approaches for imidazole derivatives. It discusses the biological importance of natural imidazoles and synthetic imidazoles used as drugs, including antifungals, antithyroid drugs, and drugs affecting the sympathetic nervous system. It also reviews conventional imidazole synthesis methods and their limitations, and modern catalytic and non-catalytic methods that offer better yields, selectivity, and green chemistry profiles.
Synthesis and Characterization of a New Cationic Surfactant Derived from 5-Ch...IJERA Editor
This document describes the synthesis and characterization of a new cationic surfactant derived from 5-Chloro-1H-indole-2,3-dione. The surfactant was synthesized in two steps: first, 5-Chloroisatin was alkylated with 1,6-dibromohexane under phase transfer catalysis conditions. Second, the product was quaternized with trimethylamine in acetone solution. The structures were confirmed using NMR spectroscopy. The critical micelle concentration of the surfactant in water was determined to be 5.10-3 M using conductivity measurements at room temperature. In conclusion, a new cationic surfactant was successfully synthesized and its micell
Visible Spectrophotometric Determination of Gemigliptin Using Charge Transfer...Ratnakaram Venkata Nadh
A visible spectrophotometric method was developed and validated for the determination of gemigliptin present in bulk drug and tablet formulation. It involves an indirect method of charge transfer complex formation in presence of NBS, metol and suphanilic acid. Gemigliptin was subjected to oxidation with excess amount of oxidant (NBS) and the unconsumed NBS oxidizes metol to give p-N-methylbenzoquinone monoamine (PNMM) which in turn forms a charge transfer complex with sulphanilic acid. Then validated the above developed method as per the current ICH guidelines. An excellent correlation coefficient (> 0.999) was found for the obtained regression equation
(y = –0.0302x + 0.928) in the range of 2.0–30.0 μg mL-1. The method was found to be simple and rapid because it does not involve any solvent extraction. The recovery levels of the drug were in the range 99.92 – 100.08.
Visible Spectrophotometric Determination of Gemigliptin Using Charge Transfer...Ratnakaram Venkata Nadh
A visible spectrophotometric method was developed and validated for the determination of gemigliptin present in bulk drug and tablet formulation. It involves an indirect method of charge transfer complex formation in presence of NBS, metol and suphanilic acid. Gemigliptin was subjected to oxidation with excess amount of oxidant (NBS) and the unconsumed NBS oxidizes metol to give p-N-methylbenzoquinone monoamine (PNMM) which in turn forms a charge transfer complex with sulphanilic acid. Then validated the above developed method as per the current ICH guidelines. An excellent correlation coefficient (> 0.999) was found for the obtained regression equation
(y = –0.0302x + 0.928) in the range of 2.0–30.0 μg mL-1. The method was found to be simple and rapid because it does not involve any solvent extraction. The recovery levels of the drug were in the range 99.92 – 100.08.
Green chemistry is an approach to chemistry that aims to prevent pollution and reduce the use of hazardous substances. It was developed by Paul Anastas and John Warner, who defined 12 principles to guide more sustainable chemical production, such as preventing waste, designing safer chemicals and catalysts, and using renewable starting materials. Green chemistry approaches include solvent-free reactions, green solvents like water, and catalytic processes to make reactions more efficient.
In this work a new prodrug polymer was
prepared with two attachment groups (amid-ester), using di
functional spacer such as ethanol amine, which could react with
polyacrylic acid producing amide group, with remain ethanol
terminal group which could react with captopril acyl chloride,
producing ester group with extended the arm substituted drug to
improve the hydrolysis and to prevent the steric effect of polymer
chains. Many advantages enhanced the prodrug of polymer. The
prepared polymers were characterized by FTIR, 1H –NMR
spectroscopies. Controlled drug release was studied in different
pH values at 37℃, using UV. Spectra with comparing with
calibration curve. The modification percentage test was studied,and swelling percentage was calculated and all physical properties were observed.
This document summarizes the synthesis and characterization of three titanium-containing metal-organic framework (MOF) photocatalysts: MIL-125, MIL-NH2, and SMIL-NH2. MIL-125 and MIL-NH2 were synthesized via a conventional solvothermal method, while SMIL-NH2 was synthesized using the same method with the addition of a nonionic surfactant. Characterization showed that SMIL-NH2 had a more uniform cylindrical morphology with smaller particle sizes of 50-250 nm and over double the surface area of MIL-NH2. Photocatalytic testing found that under blue LED light, SMIL-NH2 was able to
The document discusses coumarins, which are naturally occurring compounds with diverse pharmacological properties. Coumarins are found in many plant species and have a wide range of biological activities. Some examples mentioned include uses as anticoagulants, antimicrobials, anti-inflammatories, and more. Common coumarin derivatives discussed include warfarin and various synthetic routes for producing coumarins are also summarized such as the Perkin reaction and Pechmann condensation.
This document discusses the history and development of asymmetric hydrogenation. It begins by explaining that asymmetric hydrogenation of prochiral compounds is an efficient method for preparing optically active compounds using chiral transition metal complexes and dihydrogen. Homogeneous asymmetric hydrogenation was first reported independently in 1968 and provided early proof that catalytic asymmetric hydrogenation could occur, although yields were low. A major development was the DIPAMP ligand reported in 1975, which provided high enantioselectivity up to 96% and was used industrially to produce L-DOPA. Another landmark was the BINAP ligand developed in 1980, which significantly advanced asymmetric hydrogenation and other transition metal catalyzed reactions by improving applicability and catalytic activity.
The document discusses the principles of green chemistry. It provides 10 principles of green chemistry including prevention of waste, increasing atom economy in chemical processes, designing safer chemical syntheses, safer solvents and auxiliaries, use of renewable feedstocks, reducing unnecessary derivatization, use of catalysis, design for energy efficiency, and design of chemicals for degradation. Each principle is explained with examples to illustrate how it can be applied to make chemistry more sustainable.
Organocatalysis uses small organic molecules rather than metals to catalyze chemical reactions. Thiourea organocatalysis specifically uses thiourea derivatives to accelerate reactions through hydrogen bonding interactions. Primary amine thiourea catalysts have many advantages including being inexpensive, non-toxic, stable, and able to catalyze reactions with high enantioselectivity. The document provides procedures for synthesizing a primary amine thiourea catalyst through Boc protection of an amino acid, formation of an amide bond with benzyl amine, Boc deprotection, and conversion to an isothiocyanate derivative.
A new and efficient synthesis of 1 (4-subtitued phenyl)-3-(1-(6-(substitued-2...Alexander Decker
This document describes a new efficient method for the synthesis of 1-(4-Subtitued phenyl)-3-(1-(6-(Substitued-2-yl)pyrimidin-4-yl)piperidin-4-yl)ureas. Tert-butyl (1-(6-chloropyrimidin-4-yl)piperidin-4-yl)carbamate is coupled with various arylboronic acids using Suzuki coupling to yield intermediates. These intermediates are then deprotected and coupled with various aryl isocyanates using triethylamine to yield the final urea products in good yields. In total, twelve new 4,6-disubstituted
1. Paracetamol is generally safe at recommended doses but can cause acute liver failure and require transplantation at higher overdose doses due to its intrinsic toxicity.
2. At therapeutic doses, paracetamol is mainly metabolized through non-toxic pathways like sulfation and glucuronidation. However, at overdose levels it is oxidized by cytochrome P450 2E1 to form the toxic metabolite NAPQI.
3. NAPQI is normally detoxified by conjugating with glutathione, but an overdose depletes glutathione reserves allowing NAPQI to accumulate and cause
Organolithium compounds are useful but hazardous reagents that require careful handling. They are corrosive, flammable, and some are pyrophoric. With proper planning, protective equipment, and techniques to minimize air/moisture exposure, organolithium compounds can be used safely in the laboratory. Key safety practices include conducting experiments in well-ventilated hoods, removing combustibles from work areas, and using inert gas delivery systems.
Schiff Base Bridged Phenolic Diphenylamines for Highly Efficient and Superior...Ishfaq Ahmad
This document describes the design and synthesis of novel antioxidant additives called Schiff base bridged phenolic diphenylamines (SPDs) for lubricating oils. SPDs were designed to combine sterically hindered phenol and diphenylamine moieties into a single molecule using a Schiff base bridge. Two SPD compounds were synthesized and shown to have better thermal stability and antioxidant efficiency than commercial antioxidants. Formulations containing SPDs along with other additives also exhibited improved antioxidant performance at high temperatures, demonstrating their potential for use in the lubricant industry.
Microwave assisted synthesis and IR spectral analysis of a few complexes of 4...IRJET Journal
The document summarizes a study that synthesized chromium complexes of 4-Hydroxy-3-methoxybenzaldehyde (vanillin) using microwave-assisted oxidation with ditertiary butylchromate (TBC) in different solvents. The products were characterized using elemental analysis and Fourier transform infrared spectroscopy (FTIR). Key findings include: (1) Reaction conditions like solvent and substrate/oxidant ratio affected the products' characteristics. (2) FTIR analysis showed the presence of Cr-O, Cr=O bonds and indicated oxidation of the aldehyde group to a carboxylic acid. (3) The most efficiently synthesized product was obtained with a 1:1 substrate/oxidant ratio in 1
This document reviews 3,4-dihydropyrimidines thione, their chemistry and pharmacological potentials. It begins with background on pyrimidine structures and properties. It then discusses the chemical properties of pyrimidines and derivatives, including electrophilic and nucleophilic reactions. Biological importance is explained by pyrimidine's presence in nucleic acids, vitamins, and other biologically active compounds. Dihydropyrimidines are introduced as compounds obtained from cyclocondensation reactions. Several studies evaluating dihydropyrimidines as calcium channel blockers, antihypertensives, antibacterials, antifungals, and antioxidants are summarized.
This document provides an introduction and overview of a Small-Lab Kit developed at Chulalongkorn University for performing organic chemistry experiments safely on a small scale. The Small-Lab Kit contains basic glassware and equipment for techniques like distillation, reflux, chromatography, and more. Detailed instructions are provided for setting up experiments using the Small-Lab Kit apparatus, including assembling glassware, heating samples, and transferring liquids. The goal of the Small-Lab Kit is to enable organic chemistry experiments to be conducted conveniently and safely even without a full standard laboratory.
This document provides instructions and procedures for 12 organic chemistry laboratory experiments to be conducted by students in an Organic Chemistry Laboratory course. The experiments cover various fundamental organic chemistry techniques including synthesis of aspirin, determination of melting points, distillation, extraction, thin layer chromatography, isolation of natural products, free radical chlorination, SN1 and SN2 reactions, dehydration reactions, Grignard synthesis, computational chemistry, and multiple step synthesis. Detailed procedures are provided for each experiment along with background information on the principles and techniques involved.
This document summarizes a presentation given at a regulatory conference on generic drugs. It discusses the FDA's review of Drug Master Files (DMFs) that contain information on active pharmaceutical ingredients (APIs). Some key points:
- The FDA has transitioned DMF review staff to a new division to concentrate expertise and increase consistency in DMF/API reviews.
- Under the Generic Drug User Fee Amendments, DMFs must complete a "Completeness Assessment" and be designated "Available for Reference" for an ANDA to be filed. Metrics on assessment timelines and completeness rates are provided.
- Clarification is provided on issues like when a mixture can be considered an API, stability data
This document discusses how pharmaceutical API manufacturers can potentially control the US market for certain APIs by obtaining patents on new synthetic intermediate compounds used in the manufacturing process. It provides three key characteristics that identify the most valuable API manufacturing opportunities: 1) The synthetic route provides significant economic advantages over alternatives, 2) Part of the synthetic route is patentable, and 3) The route leaves an identifiable analytic fingerprint on the finished API. The document examines past court cases and provides a framework for analyzing potential API opportunities based on these characteristics.
This document summarizes a study investigating the relationship between the eutectic composition of resolving agents and the enantiomeric excess values obtained after resolution of racemic compounds. The study analyzed 18 individual resolutions that used resolving agents with high eutectic compositions. Very high enantiomeric excess values were obtained in all cases, suggesting that resolving agents with high eutectic compositions are well-suited for achieving highly enantiomerically enriched mixtures. The eutectic compositions of the resolving agents closely matched the enantiomeric excess values obtained for the resolved mixtures. This correlation provides evidence that the eutectic composition of a resolving agent may be an important property to consider when selecting an optimal resolving agent
Basic skills training guide hplc method development and validation- an over...bmarkandeya
This document provides an overview of HPLC method development and validation. It focuses on optimizing HPLC conditions and discusses various critical steps in analytical method development and validation. These include developing a stability-indicating HPLC method to analyze degradation products during stability studies and validating the method to demonstrate its suitability for intended use. Key aspects of method development and validation covered are sample preparation, HPLC analysis, standardization, and quantitative measures of column efficiency.
The authors attempted to reproduce a published synthesis of lysergic acid that involved the intramolecular cyclization of ethyl 6-formyl-5-(1H-indol-4-yl)pyridine-3-carboxylate (2) to form the anticipated product 3. However, under the reported reaction conditions using NaOMe or NaOH in methanol, the sole product formed was methyl 5-methoxy-4,5-dihydroindolo[4,3-f,g]quinoline-9-carboxylate (4) rather than the expected 3. Extensive experimentation and NMR analysis revealed that the cyclization reaction unexpectedly forms the aromatic and resonance-stabilized product
This document summarizes the drug approval processes in Europe and India. In Europe, there are four approval procedures - centralized, mutual recognition, decentralized, and national. The centralized procedure provides approval across the European Union and is required for certain drug classes. The other procedures allow approval in multiple or individual European countries. The process involves a clinical trial application, marketing authorization application, assessment reports, and regulatory agency reviews. In India, companies must apply to the Drugs Controller General of India and conduct clinical trials according to Schedule Y guidelines to obtain approval. The process is generally longer in India, taking 12-18 months versus approximately 12 months in Europe. Both regions have stringent requirements for new drug approval and regulate the pharmaceutical industry to protect public health
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
Sexuality - Issues, Attitude and Behaviour - Applied Social Psychology - Psyc...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
The cost of acquiring information by natural selectionCarl Bergstrom
This is a short talk that I gave at the Banff International Research Station workshop on Modeling and Theory in Population Biology. The idea is to try to understand how the burden of natural selection relates to the amount of information that selection puts into the genome.
It's based on the first part of this research paper:
The cost of information acquisition by natural selection
Ryan Seamus McGee, Olivia Kosterlitz, Artem Kaznatcheev, Benjamin Kerr, Carl T. Bergstrom
bioRxiv 2022.07.02.498577; doi: https://doi.org/10.1101/2022.07.02.498577
ESA/ACT Science Coffee: Diego Blas - Gravitational wave detection with orbita...Advanced-Concepts-Team
Presentation in the Science Coffee of the Advanced Concepts Team of the European Space Agency on the 07.06.2024.
Speaker: Diego Blas (IFAE/ICREA)
Title: Gravitational wave detection with orbital motion of Moon and artificial
Abstract:
In this talk I will describe some recent ideas to find gravitational waves from supermassive black holes or of primordial origin by studying their secular effect on the orbital motion of the Moon or satellites that are laser ranged.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
Travis Hills of MN is Making Clean Water Accessible to All Through High Flux ...Travis Hills MN
By harnessing the power of High Flux Vacuum Membrane Distillation, Travis Hills from MN envisions a future where clean and safe drinking water is accessible to all, regardless of geographical location or economic status.
Travis Hills of MN is Making Clean Water Accessible to All Through High Flux ...
Synthetic reagentsapplications
1. See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/325069368
ADVANCED ORGANIC CHEMISTRY-I (MPC 102T) UNIT-III: Synthetic Reagents
& Applications
Presentation · May 2018
DOI: 10.13140/RG.2.2.17758.95040
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2. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 1
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Aluminium isopropoxide
- It is the chemical compound usually described with the formula Al(O-i-Pr)3, where i-Pr is the isopropyl group
[–CH(CH3)2].
Description:
IUPAC name: Aluminium Isopropoxide
Other names: Triisopropoxyaluminium; Aluminium isopropanolate; Aluminium
sec-propanolate; Aluminium triisopropoxide
Chemical formula: C9H21AlO3 Molar mass: 204.25 g/mol
Appearance: white solid; Melting point: 138–1420
C; Density: 1.035 g/cm3
(solid)
Solubility
Decomposes in water
Insoluble in isopropanol
Soluble in benzene
Preparation:
- This compound is commercially available. Industrially, it is prepared by the reaction between isopropyl alcohol
and aluminium metal, or aluminium trichloride:
2Al + 6iPrOH → 2Al(O-i-Pr)3 + 3H2
AlCl3 + 3iPrOH → Al(O-i-Pr)3 + 3HCl
Applications:
1. Meerwein-Ponndorf-Verley Reduction: In a MPV reduction, ketones and aldehydes are reduced to alcohols
concomitant with the formation of acetone.
2. Reductions with Chiral Aluminum Alkoxides: The reduction of cyclohexyl methyl ketone with catalytic
amounts of Aluminium Isopropoxide and excess chiral alcohol gives (S)-1-cyclohexylethanol
3. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 2
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
3. Diastereoselective Reductions of Chiral Acetals: Reduction of 4-t-butylcyclohexanone with aluminum
isopropoxide in dichloromethane.
4. Oppenauer Oxidation: Cholestenone is prepared by oxidation of cholesterol in toluene solution with
aluminum isopropoxide as catalyst and cyclohexanone as hydrogen acceptor
5. Hydrolysis of Oximes: Oximes can be converted into parent carbonyl compounds by aluminum isopropoxide
followed by acid hydrolysis. Yields are generally high in the case of ketones, but are lower for regeneration of
aldehydes.
6. Regio- and Chemoselective Ring Opening of Epoxides: Functionalized epoxides are regioselectively
opened using trimethylsilyl azide/aluminum isopropoxide, giving 2-trimethylsiloxy azides by attack on the less
substituted carbon.
7. Preparation of Ethers. Ethers (R-O-R) are prepared from aluminum alkoxides, Al(OR)3, and alkyl halides, R-X.
4. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 3
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Diazomethane
- Diazomethane is the chemical compound CH2N2, discovered by German chemist Sir. Hans von Pechmann in
1894.
- Diazomethane is a yellow, poisonous, potentially explosive compound, which is a gas at room temperature. The
structure of diazomethane is explained using three resonance forms.
Description:
Related functional groups compounds
R-N=N=N (azide),
R-N=N-R (azo)
IUPAC name: Diazomethane Other names: Azimethylene, Azomethylene, Diazirine
Chemical formula: CH2N2 Molar mass: 42.04 g/mol Appearance: Yellow gas Odor: musty
Density: 1.4 (air=1) Boiling point: - 230
C (−90
F; 250 K) Solubility: hydrolysis in water
Molecular shape: linear C=N=N Dipole moment: polar
Preparation of Diazomethane
- Diazomethane is prepared by hydrolysis of an ethereal solution of an N methyl nitrosamide with aqueous base.
5. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 4
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Diazomethane has two common uses.
1. Conversion of carboxylic acids to methyl esters
2. Conversion of alkenes to cyclopropanes
6. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 5
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Osmium tetroxide
- Osmium tetroxide [also osmium (VIII) oxide] is the chemical compound with the formula OsO4.
Description:
Preparation of Osmium tetroxide:
- OsO4 is formed slowly when osmium powder reacts with O2 at ambient temperature. Reaction of bulk solid
requires heating to 4000
C.
Applications of Osmium tetroxide:
1. Hydroxylation of Alkenes
- Alkenes add to OsO4 to give diolate species that hydrolyze to cis-diols. The net process is called
dihydroxylation.
2. Coordination chemistry
- OsO4 is a Lewis acid and a mild oxidant. It reacts with alkaline aqueous solution to give the perosmate anion
OsO4(OH)2
2−
. This species is easily reduced to osmate anion, OsO2(OH)4
4−
.
- With tert-BuNH2, the imido derivative is produced: OsO4 + Me3CNH2 → OsO3(NCMe3) + H2O
- Similarly, with NH3 one obtains the nitrido complex: OsO4 + NH3 + KOH → K[Os(N)O3] + 2H2O
3. Biological staining
- OsO4 is a widely used staining agent used in transmission electron microscopy (TEM) to provide contrast to
the image.
4. Polymer staining
5. Osmium ore refining
IUPAC name: Osmium tetraoxide
Other names: Tetraoxoosmium; Osmium(VIII) oxide
Chemical formula: OsO4 Molar mass: 254.23 g/mol
Appearance: white volatile solid; Melting point: 40.250
C; Density: 4.9 g/cm3
Solubility
5.70 g/100 mL (100
C) and 6.23 g/100 mL (250
C) in water
375 g/100 mL (CCl4) soluble in most organic solvents, ammonium
hydroxide, phosphorus oxychloride
7. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 6
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Triphenylphosphine
- Triphenylphosphine is a common organophosphorus compound with the formula [P(C6H5)3] often abbreviated
to PPh3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds.
Description:
Preparation of Triphenylphosphine:
- Triphenylphosphine is a relatively inexpensive substance. It can be prepared in the laboratory by treatment of
phosphorus trichloride with phenylmagnesium bromide or phenyllithium.
- The industrial synthesis involves the reaction between phosphorus trichloride, chlorobenzene, and sodium.
PCl3 + 3PhCl + 6Na → PPh3 + 6NaCl
Applications of Osmium tetroxide:
1. Reagent in Mitsunobu reactions: In this reaction, a mixture of PPh3 and diisopropyl azodicarboxylate
("DIAD", or its diethyl analogue, DEAD) converts an alcohol and a carboxylic acid to an ester. The DIAD is
reduced as it serves as the hydrogen acceptor, and the PPh3 is oxidized to OPPh3.
2. Reagent in Appel reactions: In this reaction, PPh3 and CX4 (X = Cl, Br) are used to convert alcohols to
alkyl halides, forming OPPh3 as a byproduct.
PPh3 + CBr4 + RCH2OH → OPPh3 + RCH2Br + HCBr3
3. Reagent in Staudinger reactions: The Staudinger reaction is a chemical reaction of an azide with a
phosphine or phosphite produces an iminophosphorane.
R3P + R'N3 → R3P=NR' + N2
IUPAC name: Triphenylphosphane
Chemical formula: C18H15P; Molar mass: 262.29 g/mol
Appearance: white solid; Melting point: 800
C; Density: 1.1 g/cm3
Solubility: Insoluble in water; Soluble in organic solvent
Dipole moment: 1.4 - 1.44 D; Molecular shape: Pyramidal
8. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 7
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
N-Bromosuccinimide
- N-Bromosuccinimide (NBS) is a chemical reagent used in radical substitution and electrophilic addition
reactions in organic chemistry. NBS can be a convenient source of the bromine radical (Br•).
Description:
Preparation of N-Bromosuccinimide:
NBS is commercially available. It can also be synthesized in the laboratory. To do so, sodium hydroxide and bromine
are added to an ice water solution of succinimide. The NBS product precipitates and can be collected by filtration.
Applications of N-Bromosuccinimide:
1. Addition to alkenes: NBS will react with alkenes in aqueous solvents to give bromohydrins
2. Allylic and benzylic bromination: Standard conditions for using NBS in allylic and/or benzylic
bromination involves refluxing a solution of NBS in anhydrous CCl4 with a radical initiator—usually
azobisisobutyronitrile (AIBN) or benzoyl peroxide, irradiation, or both to effect radical initiation. The allylic
and benzylic radical intermediates formed during this reaction are more stable than other carbon radicals and
the major products are allylic and benzylic bromides. This is also called the Wohl–Ziegler reaction.
3. Bromination of carbonyl derivatives: NBS can α-brominate carbonyl derivatives via either a radical
pathway (as above) or via acid-catalysis
4. Hofmann rearrangement: NBS, in the presence of a strong base, such as DBU, reacts with primary amides
to produce a carbamate via the Hofmann rearrangement.
5. Selective oxidation of alcohols: It is uncommon, but possible for NBS to oxidize alcohols. It was found
that one can selectively oxidize secondary alcohols in the presence of primary alcohols using NBS in aqueous
dimethoxyethane (DME).
IUPAC name: 1-Bromo-2,5-pyrrolidinedione; Other names: N-bromosuccinimide (NBS)
Chemical formula: C4H4BrNO2; Molar mass: 177.99 g/mol
Appearance: white solid; Melting point: 175 to 1780
C; Density: 2.098 g/cm3
Solubility: 14.7 g/L (250
C) in water; insoluble in CCl4
9. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 8
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Diazopropane
Description:
Preparation:
Applications Diazopropane:
- Cyclopropanation of Alkenes: 2-Diazopropane is most commonly used to prepare gem-dimethylcyclopropyl
derivatives
- Cyclopropenation of Alkynes: Alkynes can be converted to the corresponding cyclopropene via the pyrazole
with 2-diazopropane.
- Insertion into Vinylic C-H Bonds: A common side reaction which occurs during attempted cyclopropanation of
alkenes with Diazopropane is an overall insertion into a C-H bond of the alkene. This reaction is favoured by
thermal extrusion of N2 and, for this reason, photolysis is the preferred method of decomposing pyrazolines to
cyclopropanes.
IUPAC name: 2-Diazopropane; Chemical formula: C3H6N2 ; Molar mass: 70.11g/mol
Physical Data: The reagent is a gas at room temperature.
Solubility: The reagent is most commonly prepared and used as a solution in ether.
10. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 9
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Diethyl azodicarboxylate
- Diethyl azodicarboxylate, conventionally abbreviated as DEAD and sometimes as DEADCAT, is an organic
compound with the structural formula CH3CH2O2CN=NCO2CH2CH3.
- Its molecular structure consists of a central azo functional group, RN=NR, flanked by two ethyl ester groups. This
orange-red liquid is a valuable reagent but also quite dangerous and explodes upon heating.
Description:
Preparation of Diethyl azodicarboxylate:
- Diethyl azodicarboxylate is often prepared through two-step synthesis starts from hydrazine, first by alkylation
with ethyl chloroformate, followed by treating the resulting diethyl hydrazodicarboxylate with chlorine,
concentrated nitric acid or red fuming nitric acid. The reaction is carried out in an ice bath, and the reagents are
added drop wise so that the temperature does not rise above 200
C.
Application of Diethyl azodicarboxylate:
1. Mitsunobu reaction
- DEAD is an important reagent in the Mitsunobu reaction where it forms an adduct with phosphines (usually
triphenylphosphine) and assists the synthesis of esters, ethers, amines and thioethers of alcohols.
2. Michael reaction:
- The azo group in DEAD is a Michael acceptor. In the presence of a copper(II) catalyst, DEAD assists conversion
of β-keto esters to the corresponding hydrazine derivatives
3. DEAD can be used for synthesis of heterocyclic compounds. Thus, pyrazoline derivatives convert by
condensation to α,β-unsaturated ketones:
IUPAC name: Diethyl diazenedicarboxylate;
Other names: Diethyl azidoformate, Diazenedicarboxylic acid
Chemical formula: C6H10N2O4 ; Molar mass: 174.16 g/mol
Appearance: Orange to red to orange liquid; Density: 1.11 g/cm3
Boiling point: 104.50
C
11. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 10
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Wittig reagent
- The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl
phosphonium ylide (often called a Wittig reagent) to give an alkene and triphenylphosphine oxide.
Reaction Mechanism
Application of Wittig reagents
1. Preparation of Phosphorus Ylides
- Wittig reagents are usually prepared from a phosphonium salt, which is in turn prepared by the quaternization of
triphenylphosphine with an alkyl halide. The alkylphosphonium salt is deprotonated with a strong base such as n-
butyllithium: [Ph3P+CH2R]X−
+ C4H9Li → Ph3P=CHR + LiX + C4H10
2. Structure of the Ylide:
- The Wittig reagent may be described in the phosphorane form (the more familiar representation) or the ylide form.
- The ylide form is a significant contributor, and the carbon atom is nucleophilic.
- The ylid is prepared via a two-step process: An SN
2
reaction between triphenyl phosphine and an alkyl halide
followed by treatment with a strong base such as an organolithium reagent.
12. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 11
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Titanium Chloride
Description:
Titanium tetrachloride Titanium(III) chloride Titanium(II) chloride
Chemical formula TiCl4 TiCl3 TiCl2
Molar mass 189.679 g/mol 154.225 g/mol 118.77 g/mol
Appearance Colourless liquid red-violet crystals hygroscopic black hexagonal crystals
Odor penetrating acid odor penetrating acid odor penetrating acid odor
Density 1.726 g/cm3
2.64 g/cm3
3.13 g/cm3
Melting point - 24.10
C 4250
C 1,0350
C
Boiling point 136.40
C 9600
C 1,5000
C
Solubility in water Very Soluble Very Soluble Very Soluble
Solubility soluble in ethanol, HCl soluble in acetone, acetonitrile soluble in ethanol
Preparation of Titanium tetrachloride 2 FeTiO3 + 7 Cl2 + 6 C → 2 TiCl4 + 2 FeCl3 + 6 CO
Preparation of Titanium(III) chloride 2 TiCl4 + H2 → 2 HCl + 2 TiCl3
Preparation of Titanium(II) chloride 2 TiCl3 → TiCl2 + TiCl4
Application of Titanium tetrachloride:
1. Production of titanium metal: The world's supply of titanium metal, about 250,000 tons per year, is made
from TiCl4. The conversion takes place by the reduction of the chloride with magnesium metal, and yields titanium
metal and magnesium chloride. This procedure is known as the Kroll process: 2 Mg + TiCl4 → 2 MgCl2 + Ti
(Liquid sodium has also been used instead of magnesium as the reducing agent, as in the Hunter process.)
2. Production of titanium dioxide: Around 90% of the TiCl4 production is used to make the pigment titanium
dioxide (TiO2). The conversion involves hydrolysis of TiCl4, a process that forms hydrogen chloride:
TiCl4(aq) + 2 H2O(l) <=> TiO2(s) + 4 HCl(aq)
In some cases, TiCl4 is oxidised directly with oxygen: TiCl4 + O2 → TiO2 + 2 Cl2
3. Reagent in organic synthesis: TiCl4 finds diverse use in organic synthesis, capitalizing on its Lewis acidity its
oxophilicity, and the electron-transfer properties of its reduced titanium halides. It is used in the Lewis acid
catalysed aldol addition.
4. Redox: Reduction of TiCl4 with aluminium results in one-electron reduction.
5. Complexes with simple ligands: TiCl4 is a Lewis acid as implicated by its tendency to hydrolyze.
Application of Titanium(III) chloride:
1. TiCl3 is the main Ziegler-Natta catalyst, responsible for most industrial production of polypropylene. The catalytic
activities depend strongly on the polymorph and the method of preparation.
2. TiCl3 is also a reagent in organic synthesis, useful for reductive coupling reactions, often in the presence of added
reducing agents such as zinc. It reduces oximes to imines.
13. ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- III: Synthetic Reagents & Applications
Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 12
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
Dicyclohexylcarbodiimide (DCC)
- N,N'-Dicyclohexylcarbodiimide (DCC) is a zero length coupling reagent. DCC has both biochemical and synthetic
applications.
Description:
Preparation:
- DCC has also been prepared from cyclohexyl amine and cyclohexyl isocyanide.
Application of Dicyclohexylcarbodiimide:
- DCC is mainly used in amikacin, glutathione dehydrants, as well as in synthesis of acid anhydride, aldehyde,
ketone, isocyanate; when it is used as dehydrating condensing agent.
- DCC is a carbodimide used to couple amino acids during peptide synthesis.
- Dicyclohexylcarbodiimide is an imide. Amides/imides react with azo and diazo compounds to generate toxic
gases.
- N,N'-Dicyclohexylcarbodiimide (DCC) is a zero length coupling reagent. DCC has both biochemical and
synthetic applications. This reagent can be used to couple primary amines to carboxylic acid functional groups.
DCC is soluble in many organic solvents, while the DCU by product is generally insoluble and easily removed.
IUPAC name: N,N'-dicyclohexylcarbodiimide; Other names: DCC
Chemical formula: C13H22N2; Molar mass: 206.33 g/mol
Appearance: white crystalline powder; Melting point: 340
C; Density: 1.325 g/cm3
Solubility: insoluble in water; insoluble in CCl4
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