retro synthesis.pdf
- 1. Disconnection Approach or Retrosynthetic Analysis Dr. Pinkesh G Sutariya Young Scientist (DST-SERB) Assistant Professor, Department of Chemistry, Bhavan’s Shree I. L. Pandya Arts-Science and Smt. J. M. Shah Commerce College, S. P. University V. V. Nagar, GUJARAT
- 3. Content Of the Seminar What is Disconnection Approach ? Definition Guidelines for choosing disconnection Functional group interconversion Regioselectivity, Stereoselectivity, Stereospecifity, Chemoselelectivity
- 4. What is Retrosynthesis? synthesising a target molecule ( TM, the molecule to be synthesised ), a synthetic route must be designed to give a pure sample of the TM using a convenient and efficient procedure. Usually, the best practice is to device a number of different routes for a given TM and compare them to select the best one, because the time spent in designing a synthesis is far less than that spent in lab.
- 5. Definition A logical approach for designing organic synthesis which involves breaking down of the target molecule into available starting materials by imaginary breaking of bonds ( Disconnection) and or by functional group interconversions ( FGI ) is known as disconnection approach or retrosynthetic analysis or retrosynthesis or synthesis backwards. This is the process of the synthesis design which starts with the product and works backward towards the starting material.
- 6. Retrosynthetic Analysis – Planning 1. Often the sequence of transformations that would lead to the desired compound is too complex for us to “ see “ a path from the beginning to the end. 2. We envision the sequence of steps that is required in a backward fashion,one step at a time 3. Begin by identifying immediate precursors that could be transformed to the target molecule.
- 7. 4. Then identifying the next set of precursors that could be used to make the intermediate target molecules. 5. Repeat the process until compounds that are sufficiently simple that are readily available in a typical laboratory.
- 8. Target molecule 1st precursor 2nd precursor Starting material
- 9. How this idea of the retro come ? Professor E.J.Corey originated the term retrosynthetic analysis and was the first to state its principles formely. E.J.Corey ( Harvard University , 1990 Chemistry Noble Prize winner )
- 10. Definitions of some terms used in synthesis Target molecule : The molecule to be synthesised Disconnection : An imaginary bond breaking corresponding to the reverse of a real reaction. Functional group interconversion (FGI) : The process of interconverting one functional into another during retrosynthetic analysis.
- 11. Synthesis backwards : The process of breaking down a target molecule into available starting materials by disconnection or FGI Retrosynthetic arrow : A double line arrow used to indicate the reverse of a synthetic reaction Synthon : An idelised fragment ( usually a cation or anion) resulting from a disconnection. Synthetic equivalent : A real chemical compound ( reagent ) carrying out the function of a synthon.
- 12. Guidelines for choosing disconnections Disconnections must correspond to the reverse of real and workable reactions.e.g.2,4-D For compounds consisting of two parts joined by a hetroatom, disconnect next to the hetro atom.e.g. Chlorbenside Consider alternate disconnections and choose routs that avoid chemoselectivity problems.This can often be done by disconnecting more reactive groups first.
- 13. Evaluate all the possible advantages and disadvantages of each path – determine the most efficient route for synthesis. Evaluation is based on specific restrictions and limitation of reactions in the sequence, the availability of materials , and other factors In reality , it may be necessary to try several approaches in the laboratory in order to find the most efficient or successful route.
- 14. Regioselectivity A reaction which predominantly produces one of several possible structural ( position) isomers is called regioselective reaction. Regioselective alkylation of ketones Regioselectivity in Michael reactions
- 15. Stereospecificity and stereoselectivity Diels-Alder reaction occurs in one step so that neither dienes nor dienophile has time to rotate and stereochemistry of each remains preserved in the product. Thus, with respect to the dienophileand the diene the addition is stereospecific and almost always. The Diels- Alder reaction is stereospecific.The cis dienophiles give the cis product and trans dienophile give trans product.
- 16. Chemoselectivity A Reaction in which fuctional group within a molecule reacts leaving other potentially reactive fuctional group unaltered is called a chemoselective reaction.Such a reaction is said to display Chemoselectivity. Thus, when a molecule contains two or more reactive groups and we want to react one of them but not the other , problem of chemoselectivity arises.
- 17. Guideline for that 1.When two fuctional groups of unequal reactivity are present in a molecule, the more reactive can always be made to react alone. 2.When one fuctional group can react twice , the starting material and first product will compete for the product.The reaction will be successful only if the product is less reactive than the starting material.
- 18. 3. One of the two identical groups may react if the product is less reactive than the starting material,for example partial reduction of a m – Dinitrobenzene. Reduction involves acceptance of electrons from the reducing agent. 4. One of two identical fuctional groups may react with one equivalent of reagent using the statistical effect.This is an unreliable method , but if successful it avoids protecting groups.
- 25. Conclusion of this reactions
- 42. Conclusion It is not the another chemistry or law…….its just the logical technique to synthesizing molecule in the chemistry……….
- 50. Thanking You