Designing Organic Synthesis
Designing Organic SynthesisKrishna P. KaliappanDepartment of ChemistryIndian Institute of Technology-BombayMumbai 400 076 INDIAhttp://www.chem.iitb.ac.in/ kpkkpk@chem.iitb.ac.inCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Role of Synthetic eChemistryCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis: An Ever Challenging andExciting ScienceIntroductionTechnical termsWhy to do synthesis?History of synthesisDesigning synthetic strategyRetrosynthetic analysisPractice of total synthesis (analysis and synthesis)Linear and convergent synthesisExamplesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Technical TermsØ Organic Synthesis-means the same as synthetic organicchemistryØ Total Synthesis: The chemical synthesis of a molecule from arelatively simpler starting materialsØ Semisynthesis: the synthesis of a given molecule from anadvanced precursor related to itØ Formal Synthesis: the synthesis of a key intermediate that hasbeen already converted into the target moleculeØ Partial Synthesis: the synthesis of a portion of the naturralproductCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Basic RequirementsKnowledgeCreativityArtistic TastePersistenceStaminaExperimental SkillCourage and CharacterCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Organic esTacticsCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Need for SynthesisFood for creativityScientific excitement and satisfactionDual nature as science and artIn early days, it was used to confirm the structureTesting new reagents and catalystsDiscovery of new chemistryApplications in medicine, biology and materials scienceStructural activity relationshipApplication in every day’s lifeCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
HistoryThe birth of total synthesis occurred in 19th centuryIn 1828, the first synthesis reported was by Wohler on UreaIn 1845, Kolbe coined the word synthesisThe most spectacular synthesis of 19th century was GlucoseSince then there are several outstanding synthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
HistorySimple targets were considered in early daysTheses simple targets were synthesized by often starting with compoundswhich are closely related to productsThese became impractical when the targets became more complexTo tackle this, higher level of intellectual planning and skill are requiredBetter understanding of reaction mechanismsA working knowledge of reliable reactionsProper understanding of stereochemistry and conformational analysisUse of new spectroscopic methodsIntroduction of new technique “Retrosynthetic Analysis” helped alot in achieving the synthesis of complex target moleculesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Retrosynthetic AnalysisReverse of Synthesis-The process of breaking down the TMinto available starting materials by FGI and disconnectionDisconnection is reverse operation to a reaction: An imaginarycleavage of a bond to break the molecule into starting materialsTM-Target molecule to be synthesizedFGI-Functional Group InterconversionSynthon-Fragments resulting from disconnectionSynthetic Equivalent-Actual substrates used for the forward synthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Practice of SynthesisIt involves two stagesAnalysisSynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
AnalysisSelect the target moleculeIdentify the functional groups/strategic bonds in the moleculeDisconnect bonds using known and reliable reactionRepeat disconnection as necessary to reach starting materialsDon’t compromise during the planning stageTry to use at least one novel disconnectionEvaluate all pathways and choose the most attractive routeCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Advantages of AnalysisThis leads toReadily available and inexpensive starting materialsEfficient synthetic reactionsPractical and convenient conditionsFlexibility of modification in case of pitfallsSynthesis of analogues of natural productsQuick and elegant routeCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Design and Execution of SynthesisWrite all the possible retrosynthetic pathwaysEvaluate all the pathways and go ahead withthe most attractive oneWrite the real synthesis with reagents and conditionsCollect all the relevant literature workProcure the required chemicalsExecute the SynthesisModify the plan according to unexpected failuresCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Trouble ShootingChangeEasyReaction r SupervisorDifficultP. A. Wender, Stanford UniversityCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Linear and Convergent SynthesisLinear synthesis: Synthesis of target molecule in a linear fashionConvergent synthesis: Synthesize two or more fragments and couplethem in a later stage to obtain the target moleculeConsider a synthesis that involves 5 steps with a yield of 90% each, thenCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of ChlorobenzideChlorobenzide-used to kill mites and ticksCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of Cetaben ethyl esterCetaben ethyl ester-used to lower blood lipid levelsCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
SynthesisICI-D714-Potential Anti-obesity DrugOH 2NPh BrOHPhHNPhOOHNPhOBrO OPhPhOOPhPh BrNH2HOPh PhCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. KaliappanHN
SynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of OcfentanilOcfentanil-opioid painkillerCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
SynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of FenfluoramineFenfluoramine-Neuroactive drugSynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of NafimidoneNafimidone-Antiparasitic drugSynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of Atropine MimicAtropine mimicSynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of PropranololPropranolol-Beta-Blocker,reduces blood pressureSynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Synthesis of ArildoneArildone-preventspolio and herpes simplex virusesfrom ‘unwrapping’ their DNASynthesisCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Umpolung- means reversal of polarityØ Carbon atom of the carbonyl group is electrophilic in natureand susceptible to nucleophilic attackØ A reversal of the positive polarity of the carbonyl group toformyl or acyl anion is called Umpolung process.CH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExampleCarboxylic acids could be made by the addition of a Grignardreagent to carbon dioxidecarboxylic acids can also make by nucleophilic displacement of halidesby cyanides followed by hydrolysis. This is a classical example ofUmpolung process.CH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Acyl anion derived from cyanohydrinsCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Acyl anion derived from cyanohydrinsCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Acyl anion derived from 1,3-dithianesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
SELECTIVITYØ ChemoselectivityØ RegioselectivityØ StereoselectivityCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Chemoselectivity-preferential reactivity of one functional group (FG) over anotherChemoselective reduction of C C over C OChemoselective reduction of C O over C CCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesChemoselective oxidation of allylic alcohols over other alcoholsChemoselective acetylation of amines over phenolsCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
RegioselectivityPreferential reactivity of one site over the other site of the samefunctional groupAddition of HBr to alkenesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesHydration of alkenes (Oxymercuration and Hydroboration)CH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesHydration of alkynesCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
ExamplesEpoxide openingCH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
StereoselectivityPredominant (or exclusive) formation of one of several possiblestereoisomeric productsLAH, NaBH4 affords predominantly A and bulky reducing agentslike LiAlH(OBu-t)3 gives predominantly B.CH-588: Organic Synthesis Course Slides. Instructor: Krishna P. Kaliappan
Technical Terms ! Organic Synthesis-means the same as synthetic organic chemistry ! Total Synthesis: The chemical synthesis of a molecule from a relatively simpler starting materials ! Semisynthesis: the synthesis of
Organic Synthesis What are the Essentials in Synthesis? 5 Since organic synthesis is applied organic chemistry, to stand a realistic chance of succeeding in any synthesis, the student ought to have a good knowledge-base of organic chemistry in the following areas: Protecting group chemistry Asymmetric synthesis
been developed in modern organic synthesis. The use of similar methods may open new possibilities of organic electrochemical synthesis, although a simple combination of a polar organic solvent and an ionic supporting electrolyte has been commonly used in conventional organic electro-chemistry. In modern organic synthesis, low temperatures and anhy-
Undergraduate Organic Synthesis vs. “Real” Organic Synthesis The synthesis problems you encounter in undergraduate organic chemistry are usually different from those tackled by academic research groups. First of all, Chem 30 problems ar
Advanced Organic Chemistry/ Organic Synthesis – CH 621 Ultrasound Assisted Organic Synthesis (Sonochemistry) Bela Torok Department of Chemistry
Microwave Assisted Organic Synthesis had developed in now years which has been considered superior to traditional . Journal of University of Shanghai for Science and Technology ISSN: 1007-6735 Volume 22, Issue 11, November - 2020 Page-1096. heating. Microwave assisted organic synthesis has as a new “lead” in the organic synthesis.
Solid-Supported Reagents for Organic Synthesis á A recent review on functionalized polymers with an emphasis on chiral catalysts: Synthesis 1997, 1217-1239. á Main text references: Solid Supports and Catalysts in Organic Synthesis; Smith, K., Ed.; Ellis Horwood and PTR Prentice Hall: New York, 1992.
HET618-M07A01: Synthesis of Complex Organic Molecules: Organic Molecules in Space PAGE 3 OF 57 Introduction There is a wide variety of sources of prebiotic organic molecules, including within the Earth's atmosphere, at hydrothermal vents within the Earth's oceans, plus a host of extraterrestrial sources.
The Highway Asset Management Policy and the Highway Asset Management Strategy have been developed to help us to take account of these challenges. The policy is designed to drive continuous improvement in the way we maintain our highway network to ensure that it continues to be safe serviceable and sustainable. It sets out the principles that will ensure we adopt and develop a strategic .
