1. Retrosynthetic analysis is the process of working backward from a target molecule to design a synthetic route using disconnections, functional group interconversions, and synthons.
2. The document provides examples of retrosynthetic analysis for 1-phenylhexanol, disconnecting the molecule in multiple steps through C-C bond cleavage and functional group interconversions to arrive at commercially available starting materials.
3. Key concepts discussed include using the fewest number of steps, generating stable fragments, and disconnecting at positions that correspond to reliable reactions to effectively design syntheses.
This document summarizes triphenylphosphine, an organophosphorus compound commonly used as a reducing agent. It is colorless and insoluble in water, with a melting point of 80°C and boiling point of 377°C. The document discusses its preparation and applications, including in Mitsunobu reactions, Appel reactions, and for preparing Wittig reagents.
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.
N-bromosuccinimide (NBS) is a white powder or crystals that is a convenient source of bromine for radical substitution and electrophilic addition reactions. It is more easily handled than bromine. NBS can be used to brominate alkenes, allylic and benzylic positions, carbonyl compounds, aromatic compounds, and perform Hofmann rearrangements. Side reactions include formation of α-bromoketones, dibromo compounds, and conjugates of succinimide. NBS is commercially available but can also be prepared by adding sodium hydroxide and bromine to an ice water solution of succinimide.
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.
Oxidation (Unit Process-1) Pharmaceutical Process Chemistry AikanGupta
The document discusses various types of oxidation reactions that are important in organic chemical synthesis, including dehydrogenation, peroxidation, introduction of oxygen atoms, and the oxidation of compounds containing sulfur, nitrogen, ethylenic bonds, and other functional groups. Examples are provided of industrial oxidation processes such as the production of vanillin, camphor, benzaldehyde, quinone, and dihydroxy fatty acids. Oxidizing agents and reaction conditions that influence the products are also described.
The document discusses the Ugi reaction, a multi-component reaction first reported in 1959 by Prof. Ivar Karl Ugi. The Ugi reaction involves a ketone or aldehyde, an amine, an isocyanide, and a carboxylic acid to form a bis-amide derivative. It is exothermic, fast, and high-yielding. By varying the substituents, large chemical libraries can be synthesized from a single reaction. The Ugi reaction is used in combinatorial chemistry and drug development, such as for the HIV drug Crixivan.
This document summarizes triphenylphosphine, an organophosphorus compound commonly used as a reducing agent. It is colorless and insoluble in water, with a melting point of 80°C and boiling point of 377°C. The document discusses its preparation and applications, including in Mitsunobu reactions, Appel reactions, and for preparing Wittig reagents.
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.
N-bromosuccinimide (NBS) is a white powder or crystals that is a convenient source of bromine for radical substitution and electrophilic addition reactions. It is more easily handled than bromine. NBS can be used to brominate alkenes, allylic and benzylic positions, carbonyl compounds, aromatic compounds, and perform Hofmann rearrangements. Side reactions include formation of α-bromoketones, dibromo compounds, and conjugates of succinimide. NBS is commercially available but can also be prepared by adding sodium hydroxide and bromine to an ice water solution of succinimide.
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.
Oxidation (Unit Process-1) Pharmaceutical Process Chemistry AikanGupta
The document discusses various types of oxidation reactions that are important in organic chemical synthesis, including dehydrogenation, peroxidation, introduction of oxygen atoms, and the oxidation of compounds containing sulfur, nitrogen, ethylenic bonds, and other functional groups. Examples are provided of industrial oxidation processes such as the production of vanillin, camphor, benzaldehyde, quinone, and dihydroxy fatty acids. Oxidizing agents and reaction conditions that influence the products are also described.
The document discusses the Ugi reaction, a multi-component reaction first reported in 1959 by Prof. Ivar Karl Ugi. The Ugi reaction involves a ketone or aldehyde, an amine, an isocyanide, and a carboxylic acid to form a bis-amide derivative. It is exothermic, fast, and high-yielding. By varying the substituents, large chemical libraries can be synthesized from a single reaction. The Ugi reaction is used in combinatorial chemistry and drug development, such as for the HIV drug Crixivan.
This document summarizes different types of reduction reactions. It discusses the mechanism of reduction reactions as the removal of oxygen or addition of hydrogen. It describes two types of catalysts - homogeneous and heterogeneous. It also outlines several specific types of reduction reactions including catalytic hydrogenation, hydride transfer reactions, dissolving metal reactions, replacement of oxygen by hydrogen, reductive coupling, and reduction with cleavage. Key reducing agents mentioned are lithium aluminum hydride, sodium borohydride, and various transition metals.
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.
SIDE REACTION OCCUR IN PEPTIDE YNTJESIS ARE DISCUSSED HERE WITH ITTATED PROTON, PROTONATIONS RACEMIZATION, INITIATED ACTIVITY, ACYLATION, ALKYLATION, OVERACTIVATION
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.
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,
This document discusses retrosynthetic analysis and disconnection strategies for planning the synthesis of drug molecules. It defines key terms like retrosynthesis, synthons, and functional group interconversions. It provides guidelines for disconnecting different types of bonds and functional groups in a molecule, including C-X, C-C, and multiple bonds/groups. The goal is to break down the target molecule into stable and readily available starting materials by applying principles of retrosynthetic analysis.
This document provides an introduction to retrosynthesis, which involves working backwards from a target molecule to devise a synthetic route. It discusses key terminology like disconnections, synthons, and functional group interconversions. The principles of retrosynthesis are disconnection, where an imaginary bond cleavage corresponds to a synthetic reaction, and functional group interconversion, which involves changing one functional group to another. Examples of retrosynthesis are provided for drugs like ofornine and paracetamol to illustrate these concepts.
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.
The Mannich reaction involves the condensation of an enolizable carbonyl compound, an amine or ammonia, and formaldehyde to form an aminomethyl derivative known as a Mannich base. Ketones are most commonly used as the carbonyl compound. The reaction proceeds via the generation of an imine intermediate from the carbonyl compound and amine, which then reacts with formaldehyde to form the Mannich base. Mannich bases have applications in synthesizing natural products like alkaloids and building ring systems.
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
Pyridinium chlorochromate (PCC) is a mild and selective oxidizing reagent used to convert primary and secondary alcohols to aldehydes and ketones respectively. It was first described in 1975 by Elias Corey and J. William Suggs as an efficient reagent for alcohol oxidation. PCC is prepared by adding pyridine to a solution of chromium trioxide in hydrochloric acid. It is a stable, yellow-orange solid that is soluble in organic solvents. PCC oxidizes alcohols more selectively than related reagents like Jones reagent with little chance of over-oxidation to carboxylic acids. While still used, its usage has declined in recent decades as
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.
The document discusses several named organic reactions including the Ugi reaction, Ullmann reaction, and Brook rearrangement. The Ugi reaction involves combining an isocyanide, carboxylic acid, amine, and carbonyl compound to form diamides. The Ullmann reaction involves copper-catalyzed coupling of aryl halides to form symmetric biaryls. The Brook rearrangement involves a rearrangement where an organosilyl group switches position with a hydroxyl proton over a carbon-oxygen bond in the presence of a base to form a silyl ether.
This document discusses the use of protecting groups in organic synthesis. It provides examples of common protecting groups for alcohols, including trialkylsilyl ethers, benzyl ethers, and acetate esters. Methods for introducing and removing these protecting groups are described. The document also discusses protecting groups for amines, such as Boc and phthaloyl, along with their introduction and removal conditions. Finally, examples of acetal and ketal protecting groups for carbonyl compounds are briefly mentioned.
The document discusses retrosynthesis, which is the process of working backward from a target organic compound to develop a synthetic route. It involves imagining the cleavage of bonds to form synthons, which are idealized fragments represented as ions. Key steps in retrosynthesis are disconnection, which breaks bonds, and functional group interconversion, which changes one functional group to another. The goal is to develop the most efficient synthesis using readily available starting materials and reagents.
1) The document discusses the synthon approach, which involves breaking down a target molecule into simpler starting materials through imaginary bond breaking (disconnection) or functional group interconversion.
2) Key terms are defined, including disconnection, synthon, and functional group interconversion. Basic rules of disconnection are outlined.
3) An example of using the synthon approach to synthesize the drug benzocaine from toluene is provided, outlining the multi-step reaction pathway and identifying specific synthons.
This document discusses the synthon approach to retrosynthetic analysis in organic synthesis. It defines key terms like disconnection, synthon, and functional group interconversion. The document outlines basic rules for disconnection, such as generating stable fragments and minimizing the number of fragments. It provides guidelines for good retrosynthesis and discusses the use of synthons in the multi-step synthesis of benzocaine from toluene as an example.
This document summarizes different types of reduction reactions. It discusses the mechanism of reduction reactions as the removal of oxygen or addition of hydrogen. It describes two types of catalysts - homogeneous and heterogeneous. It also outlines several specific types of reduction reactions including catalytic hydrogenation, hydride transfer reactions, dissolving metal reactions, replacement of oxygen by hydrogen, reductive coupling, and reduction with cleavage. Key reducing agents mentioned are lithium aluminum hydride, sodium borohydride, and various transition metals.
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.
SIDE REACTION OCCUR IN PEPTIDE YNTJESIS ARE DISCUSSED HERE WITH ITTATED PROTON, PROTONATIONS RACEMIZATION, INITIATED ACTIVITY, ACYLATION, ALKYLATION, OVERACTIVATION
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.
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,
This document discusses retrosynthetic analysis and disconnection strategies for planning the synthesis of drug molecules. It defines key terms like retrosynthesis, synthons, and functional group interconversions. It provides guidelines for disconnecting different types of bonds and functional groups in a molecule, including C-X, C-C, and multiple bonds/groups. The goal is to break down the target molecule into stable and readily available starting materials by applying principles of retrosynthetic analysis.
This document provides an introduction to retrosynthesis, which involves working backwards from a target molecule to devise a synthetic route. It discusses key terminology like disconnections, synthons, and functional group interconversions. The principles of retrosynthesis are disconnection, where an imaginary bond cleavage corresponds to a synthetic reaction, and functional group interconversion, which involves changing one functional group to another. Examples of retrosynthesis are provided for drugs like ofornine and paracetamol to illustrate these concepts.
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.
The Mannich reaction involves the condensation of an enolizable carbonyl compound, an amine or ammonia, and formaldehyde to form an aminomethyl derivative known as a Mannich base. Ketones are most commonly used as the carbonyl compound. The reaction proceeds via the generation of an imine intermediate from the carbonyl compound and amine, which then reacts with formaldehyde to form the Mannich base. Mannich bases have applications in synthesizing natural products like alkaloids and building ring systems.
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
Pyridinium chlorochromate (PCC) is a mild and selective oxidizing reagent used to convert primary and secondary alcohols to aldehydes and ketones respectively. It was first described in 1975 by Elias Corey and J. William Suggs as an efficient reagent for alcohol oxidation. PCC is prepared by adding pyridine to a solution of chromium trioxide in hydrochloric acid. It is a stable, yellow-orange solid that is soluble in organic solvents. PCC oxidizes alcohols more selectively than related reagents like Jones reagent with little chance of over-oxidation to carboxylic acids. While still used, its usage has declined in recent decades as
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.
The document discusses several named organic reactions including the Ugi reaction, Ullmann reaction, and Brook rearrangement. The Ugi reaction involves combining an isocyanide, carboxylic acid, amine, and carbonyl compound to form diamides. The Ullmann reaction involves copper-catalyzed coupling of aryl halides to form symmetric biaryls. The Brook rearrangement involves a rearrangement where an organosilyl group switches position with a hydroxyl proton over a carbon-oxygen bond in the presence of a base to form a silyl ether.
This document discusses the use of protecting groups in organic synthesis. It provides examples of common protecting groups for alcohols, including trialkylsilyl ethers, benzyl ethers, and acetate esters. Methods for introducing and removing these protecting groups are described. The document also discusses protecting groups for amines, such as Boc and phthaloyl, along with their introduction and removal conditions. Finally, examples of acetal and ketal protecting groups for carbonyl compounds are briefly mentioned.
The document discusses retrosynthesis, which is the process of working backward from a target organic compound to develop a synthetic route. It involves imagining the cleavage of bonds to form synthons, which are idealized fragments represented as ions. Key steps in retrosynthesis are disconnection, which breaks bonds, and functional group interconversion, which changes one functional group to another. The goal is to develop the most efficient synthesis using readily available starting materials and reagents.
1) The document discusses the synthon approach, which involves breaking down a target molecule into simpler starting materials through imaginary bond breaking (disconnection) or functional group interconversion.
2) Key terms are defined, including disconnection, synthon, and functional group interconversion. Basic rules of disconnection are outlined.
3) An example of using the synthon approach to synthesize the drug benzocaine from toluene is provided, outlining the multi-step reaction pathway and identifying specific synthons.
This document discusses the synthon approach to retrosynthetic analysis in organic synthesis. It defines key terms like disconnection, synthon, and functional group interconversion. The document outlines basic rules for disconnection, such as generating stable fragments and minimizing the number of fragments. It provides guidelines for good retrosynthesis and discusses the use of synthons in the multi-step synthesis of benzocaine from toluene as an example.
Retrosynthetic analysis, definition, importance, disconnection approach, one group two group disconnection logical and illogical disconnection approach compounds containing two nitrogen atom retrosynthetic analysis of camphor, cartisone, reserpine
The document discusses methodology in organic synthesis, including examples of natural products. It describes convergent and divergent synthesis strategies. Convergent synthesis involves coupling molecular fragments through independent synthesis to improve reaction yields compared to linear synthesis. Divergent synthesis starts from a central core and generates a library of compounds through successive additions. Functional group interconversion and addition techniques are discussed to allow for disconnection of target molecules during retrosynthetic analysis.
Retrosynthes analysis and disconnection approach ProttayDutta1
Retrosynthetic analysis is a technique used to plan organic syntheses by working backwards from the target molecule. It involves mentally deconstructing the target molecule through sequential disconnections and functional group transformations until commercially available starting materials are reached. Each disconnection produces synthons, which are idealized fragments that represent possible reaction precursors. Common types of disconnections include C-X, C-C, and carbonyl bonds. The goal of retrosynthesis is to simplify the target structure and design multiple possible synthesis routes leading from simple starting materials to the target. It helps chemists discover efficient syntheses by considering the reactivity, selectivity, and availability of materials at each step.
An approach for designing organic synthesis which involves breaking down of target molecule into available starting material by imaginary breaking of bonds (disconnection) and/or by functional group interconversion is known as disconnection approach or retrosynthesis or synthesis backward.
The C-X disconnection approach is mainly applicable to a carbon chain attached to any of the heteroatoms like O, N, or S. Here, a bond joins the heteroatom (X) to the rest of the molecule like a C-O, C-N, or C-S group. This point is good point to initiate a disconnection. This is called a ‘One-group’ C-X disconnection as one would need to identify only one functional group like ester, ether, amide etc. to make the disconnection.
How to choose a disconnection?
These are the few general strategy which are important points introduced which apply to the whole of synthetic design rather than one particular area. The main choice is between the various disconnection, even such a simple disconnection as the following alcohol can be disconnected.
We want to get back to simple starting materials and we shall do if we disconnect the bond which are:
Towards the middle of the molecule thereby breaking into two reasonably equal halves rather than chopping off one or two carbon atoms from the end and,
At a branch as this is more likely to give straight chain fragments and these are more likely to be available.
Disconnections very often take place immediately adjacent to, or very close to functional groups in the target molecule. This is pretty much inevitable, given that functionality almost invariably arises from the forward reaction.
A simple example is the weedkiller propanil used on rice fields. Amide disconnection gives amine obviously made from o-dichlorobenzene by nitration and reduction. All positions around the ring in o-dichlorobenzene are about the same electronically but steric hindrance will lead to dichloronitrobenzene being the major product
This compound was needed for some research into the mechanisms of rearrangements. We can disconnect on either side of the ether oxygen atom, but (b) is much better because (a) does not correspond to a reliable reaction: it might be hard to control selective alkylation of the primary hydroxyl group in the presence of the secondary one.
The disconnections we have made so far have all been of C–O, C–N, or C–S bonds, but, of course, the most important reactions in organic synthesis are those that form C–C bonds. We can analyze C–C disconnections in much the same way as we’ve analyzed C–X disconnections.
The Zeneca drug propranolol is a beta-blocker that reduces blood pressure and is one of the top drugs worldwide. It has two 1,2-relationships in its structure but it is best to disconnect the more reactive amine group first.
Arildone is a drug that prevents polio and herpes simplex viruses from ‘unwrapping’ their DNA, and renders them harmless.
Basic Concepts Of Retrosynthesis (Part1)munirnizami
1. The document discusses the basic concepts of retrosynthetic analysis in organic synthesis. Retrosynthesis is the process of working backward from a target molecule to design synthetic routes using disconnections and functional group interconversions.
2. Key concepts include synthons, which are idealized fragments formed by imagined bond cleavages, and synthetic equivalents, which are actual reagents that can function as those synthons.
3. Effective retrosynthesis requires understanding reaction mechanisms and reliable reactions, as well as considering availability of starting materials and stereochemistry.
Basic Concepts Of Retrosynthesis (Part1)munirnizami
1. The document discusses the basic concepts of retrosynthetic analysis in organic synthesis. Retrosynthesis is the process of working backward from a target molecule to design synthetic routes using disconnections and functional group interconversions.
2. Key concepts include synthons, which are idealized fragments formed by imagined bond cleavages, and synthetic equivalents, which are actual reagents that can function as those synthons.
3. Effective retrosynthesis requires understanding reaction mechanisms and reliable reactions, as well as considering availability of starting materials and stereochemistry.
For B Pharmacy and M Pharmacy Students
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The document discusses chemical kinetics modeling of combustion reactions. It describes the need for detailed chemical kinetic models to understand fuel oxidation, pollutant formation, and combustion chemistry phenomena. Complex fuel mixtures require the use of reduced model fuels and reaction mechanisms. Detailed mechanisms are generated using generic reaction classes and can involve hundreds to thousands of species and reactions. Mechanism reduction techniques like lumping and skeletal reduction are used to reduce mechanism size and computational cost for modeling applications.
Essential Biology 3.8 8.1 C4 Photosynthesis (Core, AHL & Op C)Stephen Taylor
The document provides information and questions about photosynthesis and cellular respiration. It begins with instructions to highlight command terms from the objectives in different colors and complete a self-assessment rubric. The bulk of the document consists of multiple choice and written questions about topics like the light and dark reactions of photosynthesis, limiting factors, and comparisons to cellular respiration. It includes diagrams of chloroplast structure and the Calvin cycle for labeling. Sources are to be cited using the CSE citation method.
Organic chemistry is the study of carbon-containing compounds. It was originally thought that compounds found in living things were fundamentally different than non-living compounds, but we now know this is not true. Organic structures can be represented using condensed or skeletal structures, assuming carbons and hydrogens are present. Common organic reactions include substitution, elimination, and addition reactions. Substitution reactions involve replacing one group with another. The SN2 substitution reaction proceeds in one step with simultaneous attack of the nucleophile and departure of the leaving group. This results in inversion of configuration at any chiral centers.
Students analyzed an enediyne compound, C11H5O4, using computational chemistry methods like DFT and various spectroscopic techniques. The FT-NMR (1H and 13C) and FT-Raman spectra were obtained and compared to literature values. DFT calculations using B3LYP, MP2, and RHF methods helped students understand the vibrational modes, NMR chemical shifts, and frontier molecular orbitals like HOMO and LUMO of the compound. Experimental UV-Vis and FT-IR spectra were also collected and analyzed. The computational results provided insight into the structural properties and reactivity of this biologically relevant enediyne compound.
The document discusses retrosynthetic analysis, a technique developed by Elias Corey for planning organic syntheses. It involves deconstructing a target molecule into simpler precursor structures by applying the reverse of known reactions. Each precursor is then further deconstructed until commercially available starting materials are reached, mapping out possible synthesis routes. This allows for more systematic planning than trial-and-error methods. Retrosynthesis generates a "tree" of intermediates and pathways that is then pruned according to availability and strategy to give practical synthesis routes. It can reveal multiple starting materials or convergent syntheses for more efficient production.
I use this lab sequence over a couple of lessons to get to grips with some basics of different types of reactions, balancing, writing formulas and problem-solving.
The document discusses retrosynthetic analysis, a technique used in organic synthesis planning. It involves deconstructing a target molecule into simpler precursor structures by applying the reverse of known reactions. This is done iteratively until commercially available starting materials are reached. Key points discussed include:
- Identifying functional groups and reactive sites ("retrons") that suggest disconnection points
- Applying topological and transform-based strategies to simplify the target structure
- Generating a retrosynthetic tree showing possible routes from precursors to the target
- Choosing disconnections that make the precursors easier to synthesize than the target
- Retrosynthetic analysis, also known as disconnection approach or retrosynthesis, is a logical method for designing organic syntheses by breaking down target molecules into simpler precursor molecules through imaginary bond breaking or functional group interconversions.
- The process involves envisioning the synthetic route in reverse, starting from the target molecule and identifying immediate precursor molecules that could be transformed into the target molecule in one step.
- This is repeated backwards until arriving at readily available starting materials. Guidelines for effective disconnections include corresponding to known reaction reversals and avoiding chemoselectivity problems.
Modelling Functional Motions of Biological Systems by Customised Natural Moves.Samuel Demharter
I present a protocol to study structural mechanisms in biological molecules. We demonstrate its use on a protein and a DNA epigenetics system.
Protocol steps - 1: Define Hypothesis, Step 2: Choose Natural Moves, Step 3: Generate Test Cases, Step 4: Simulation & Evalutation.
Similar to Abhi cho 353 advanced org synthesis ppt (20)
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
PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
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.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
Targeting Hsp90 and its pathogen Orthologs with Tethered Inhibitors as a Diagnostic and Therapeutic Strategy for cancer and infectious diseases with Dr. Timothy Haystead.
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.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
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.
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
1. RETROSYNTHETIC APPROCH
TO ORGANIC SYNTHESIS
[CHO- 353] [Part – B]
Prof. Gaikwad Abhijit A.
M.Sc. B.ed. SET, TIFR.
Department of Chemistry
N.V.P. Mandal’s College Lasalgaon
5. DEFINATION
The preparation of a desired
organic compound from a readily
available starting material is known
as organic synthesis
[Synthesis---- singular]
[Syntheses--- plural]
10. Reasons for synthesizing
Organic Compound
1. Proof of structure of a natural
compound
2. To prepare compounds that are
useful to mankind e.g.
pharmaceutical, polymers, dyes etc.
11. Reasons for synthesizing
Organic Compound
3. To prepare specific compounds
to study reaction mechanisms or
biological metabolism e.g. labelled
compounds
4. For the intellectual challenges –
new problems demand new solutions
and can lead to the development of
NEW CHEMISTRY, reagents, etc.
13. BOND POLARITY
(Polar covalent bond)
Most heteroatom are more
electronegative than carbon
i.e. O, N, Br, Cl,
Partial positive charge appears
on carbon (+)
14. BOND POLARITY
(Polar covalent bond)
Si, Mg,Li are electropositive
compared with the carbon
The polarity in these case is
reversed
partial negative charge
appears on carbon (-)
15. ARROW NOTATION
Simple reaction arrow “reacts to give”
Delocalisation arrow
“two different ways to draw the same
Curved arrow
delocalised structures”
Equilibrium arrow
“two structures are interconverting”
Fish-hook arrow
“motion of two electrons”
“motion of one electron”
Retrosynthesis
arrow
“could be made from”
17. RETROSYNTHETIC ANALYSIS
1.The process of WORKING BACKWARD
from the TM in order to devise suitable
synthetic route
2.Retrosynthetic Analysis can be done
bytwo methods
a) Disconnection
b) Functional Group Interconversion
18. DISCONNECTION
1.A paper operation involving an
imagined cleavage of a bond.
2.As a result of disconnection
usually negative ion and
positive ion are formed which
are called ‘SYNTHONS’
3.Disconnection is shown by a
wavy line like ~ or VVVVVVVV
24. SYNTHONS
These are idealized fragments
Synthons are shown by a + or
– sign like anion or cation
(Not real anion or cation)
May or may not be intermediate
in the corresponding reactions
25. 25
1. Introduction
• Synthon term was coined by Prof. E.J.Corey in mid 1960’s
• Elegant and more systematic approach
• .
• Depends on perception of structural feature in the reaction product and manipulation of
structures in the reverse synthetic sense.
• Designate ‘structural units within a molecule which are related to possible synthetic
operations’.
• Helps in eliminations of low probability variants.
26. Target
Molecul
e
Disconnect
ed
Precursors
• This process of analysis produces simple starting material and shows different
pathway.
•From this precursor the cheap starting material has been selected for the synthesis
of the target molecule or desired molecule.
26
Process called
Analysis
27. 27
-
•Synthon can be divided in to following two types – They
are derived from a reagents with functional groups
1. Donor Synthon eg. - C2H5 is ethyl donor synthon from - C2H5Li
2. Acceptor Synthon eg. - C2H5 is ethyl acceptor synthon from – C2H5I+
28. 28
2. Definition of Terms
a. Disconnection :
It is an imaginary process in which the bonds are broken to get simple possible starting
materials. This is also called as "transform". A curred line is used at the pointof
disconnection of bond and a double line arrow (=>) is used for representing
disconnection.
b. Synthon :
It is an idealized fragment obtained by disconnection and may or may not be
involved in the reaction but helps us to work out reagents to be used.
Example – R X => R+ + X- (Synthon)
30. a. Functional Group Identification :
It is the operation of changing one functional group to another either by interconversion,
substitution, elimination, oxidation or reduction, so that the disconnection becomes easier.
Example :
NO2
NH2
FGI
H3C COOH H3C CN
FGI
30
31. 3. Basic Rules In Disconnection
•When one thinks of retrosynthetic analysis of a target molecule, it is a question ‘where
the disconnection is to be done?’. This is generally governed by certain rules:
Rule -1
Disconnection of a bond should be done in such a way that it produces stable fragments.
While carrying out a disconnection the molecule is broken down by one bond at a time.
e.g. O2N
R
-C NO2 +
31
C R+
32. Rule -2
The number of fragments generated by disconnection should be as small as possible. So,
the synthesis of target molecule can be carried out in possible steps.
e.g.
O O O O
32
+
33. Rule -3
A bond joining a carbon to a hetero atom always broken with the electron pair onhetero
atom. e.g
Rule -3
Sometimes a disconnection carried out does not generate sufficient stabilised fragments,
but such fragments can be obtained by using FGI or by introducing an additional electron
withdrawing group and then removing it after synthesis.
C N C
+
+ N
-
33
34. 34
Guidelines For Disconnection :
(i) Make the analysis in such a way that the synthesis become as short as possible.
(ii) Use the only disconnections corresponding to known reliable reaction.
(iii) Disconnect C-X bonds especially two group disconnections.
(iv) Choose the disconnection corresponding to the highest yielding reaction, if known.
(v)Disconnect back to recognisable starting materials or to compounds which can be
easily be made.
(vi) Disconnect C-C bonds according to the functional groups in the molecule , if possible
- disconnect at the middle of the molecule.
35. 35
Guidelines For Good Synthesis :
In retrosynthetic approach, there are usually more than one way to synthesize a
compound. But the selection of a best desirable route is important. Thereafter the
following factors are considered in order to decide which one of the routes is safe and
simple to employ.
(i) Availability of starting material.
(ii) Which route involves the least number of separation operations ?
(iii) Which route gives the highest overall yield ?
(iv) How expensive are the starting materials and reagents ?
(v) Which route includes least time and effort ?
36. Retrosynthetic pathway : Benzocaine from
toluene
4. Use of Synthon In Synthesis of Some Medical or Organic
OEth
O
H2N
C-O
H2N
OH
O
FGI
O2N
OH
O
2O N
Me
C-NMe
Benzocaine :
• Toluene is readily available starting
material
• Me is activating and ortho-/para-
directing
• We know reagents for the synthon NO2
36
40. DESIGNING A SYNTHESIS
Recognize the functional
groups in the target molecule
Disconnect by methods
corresponding to known and
reliable reactions
Repeat as necessary to reach
available starting material
41. SYNTHESIS
Write out the plan according
to the analysis, adding
reagents and conditions
Modify the plan according to
unexpected failure in the
laboratory
66. What is the best
synthesis?
Availability of the reagent
Synthetic step should be
kept minimum unless there
is an advantage of FGI
Disconnection of C-C bond
should be in the center of a
67. Help Tim to get a nibble
of the Birthday Cake!
73. CONTENTS
Definition of Functional Group
Interconversion (FGIs)
Importance of FGIs
Functional group containing
heteroatoms
Unsaturated hydrocarbons
Removal of Functional Groups
74. Definition of Functional
Group Interconversion
The process of writing
one functional group
for another to help
synthetic planning is
known as FGI
76. Why FGI is needed?
A TM containing more than
one functional group, one
functional group may interfere
with desired reaction on
second functional group during
a synthesis.
77. Why FGI is needed?
This problem can be solved
into ways
a) Use of protecting group
b) Change in synthetic strategy
(using FGI)
78. Importance of FGIs
It helps in identifying suitable
disconnection.
Consider the synthesis of
ketone containing a double
bond.
Alkenes may be prepared by
the dehydration of alcohol.
79. Importance of FGIs
O
Ph Ph
TM
First step in the retrosynthetic
analysis of TM could be functional
group interconversion to an alcohol
But which alcohol ?
84. a) Carboxylic acid and their
derivatives
Compounds in this class are the highest
oxidation level of organic compounds
It includes
Carboxylic acid (RCO2H)
Esters/lactone (RCOO2R)
Amide/lactam (RCONHR)
They may be interconverted by a series
of simple reactions
85. Transformations of
carboxylic acid derivatives
R OH
O
R Cl
O
SOCl2
or PCl5
H2O
R NH2
ONH3
R OR'
O
H2OH2O
H+/
R’OH
RO-
R C N2H O
R O R'
O O
86. b) Aldehydes, ketones and
their derivatives
Functional groups in this class
are at lower oxidation level
than class (a)
It includes the features C=X in
which the carbon atom is
bonded directly to either
hydrogen or carbon.
87. b) Aldehydes, ketones and
their derivatives
The group includes
Aldehydes (RHC=O)
Ketones (RR’C=O)
Imines (RR’C=NR”)
Hydrazones (RR’C=NNHR”)
Oximes (RR’C=NOH)
89. c) Alcohols and their
derivatives
Apart from Alcohols (ROH)
themselves, this class includes
Amines (RNH2)
Thiols (RSH)
Disulphides (RSSR)
Ethers (ROR)
Alkyl halides (RX)
91. Use of a sulphonic ester
as a leaving group
R OH R OSO2R'
R’SO2Cl
Nu-
R Nu + R’SO3
-
92. Interconversions between
the three oxidation levels
a,b & c above
To move between groups
classified in the previous
section, it is necessary to
perform a reduction or
oxidation at some stage.
93. Oxidation
Many methods have been
developed for the oxidation of
organic compounds.
It is possible to transform a
low oxidation level FG into any
group of higher level.