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    DISCONNECTION APPROACH

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    divya sachdeva
    DISCONNECTION APPROACH DEFINITION SYNTHONS AND SYNTHETIC EQUIVALENT GUIDELINES FOR CHOOSING DISCONNECTION FUNCTIONAL GROUP ANALYSIS

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    © All Rights Reserved

    DISCONNECTION APPROACH

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    divya sachdeva
    6 views18 pages
    DISCONNECTION APPROACH DEFINITION SYNTHONS AND SYNTHETIC EQUIVALENT GUIDELINES FOR CHOOSING DISCONNECTION FUNCTIONAL GROUP ANALYSIS

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    © © All Rights Reserved

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    DISCONNECTION APPROACH DEFINITION SYNTHONS AND SYNTHETIC EQUIVALENT GUIDELINES FOR CHOOSING DISCONNECTION FUNCTIONAL GROUP ANALYSIS

    Copyright:

    © All Rights Reserved
    6 views18 pages

    DISCONNECTION APPROACH

    Uploaded by

    divya sachdeva
    DISCONNECTION APPROACH DEFINITION SYNTHONS AND SYNTHETIC EQUIVALENT GUIDELINES FOR CHOOSING DISCONNECTION FUNCTIONAL GROUP ANALYSIS

    Copyright:

    © All Rights Reserved
    of 18

    DISCONNECTION APPROACH

    DEFINITION
    SYNTHONS AND SYNTHETIC
    EQUIVALENT
    GUIDELINES FOR CHOOSING
    DISCONNECTION
    FUNCTIONAL GROUP ANALYSIS
    DEFINITION
    A logical approach for designing organic
    syntheses which involves breaking down of the
    target molecule into available starting
    materials by imaginary breaking of bonds
    (disconnection) or by functional group
    interconversion (FGI) is known as
    disconnection approach or retrosynthetic
    analysis or synthesis backward.
    This is the process of
    synthesis design which starts with the product
    and works backward towards the starting
    material
    A double line arrow ( ) called a
    retrosynthetic arrow is commonly used
    to indicate a reaction written
    backwards; the actual reaction is in
    reverse.
    Z X+Y
    The following ester can be prepared
    from benzyl alcohol and benzoyl
    chloride OH + Cl
    Definitions of some terms used in
    synthesis
     Target molecule: The molecule to be
    synthesised
    Disconnection : An imaginary bond
    breaking corresponding to
    the reverse of real reaction.
    Functional The process of
    interconverting
    group : one functional group into
    interconversion another during
    retrosynthetic
    analysis.
    Retrosynthetic The process of breaking
    down a
    analysis or : target molecule(TM)
    Retrosynthetic A double line arrow
    ( ),
    arrow : used to indicate the
    reverse
    of a synthetic
    reaction

    Synthon: An idealised fragment


    resulting from a
    disconnectiion

    Synthetic A real chemical


    compound
    equivalent carrying out the
    function of a
    SYNTHONS AND SYNTHETIC EQUIVALENTS

    Synthons are idealised fragments, usually


    cations or anions resulting from a
    disconnection.
    In the
    example of
    Paracetamol which is an amide and can be
    disconnected either to amine + acyl chloride
    or to amine + C-N
    anhydride.
    bond NH
    2
    Cl
    +
    or
    Which reagent is best can only be
    determined by experimentation.
    Commercially, paracetamol is
    prepared from p-aminophenol and
    acetic anhydride largely because by-
    product, acetic acid is easier to handle
    than HCl For example
    we can depict both acyl chloride and
    anhydride in the above scheme as a
    single idealised reagent, viz., the
    cation of electrophilic acetyl group
    (CH3 C+ =O). Such idealised fragment
    The synthesis of 2,4-D. The most
    reasonable disconnection of an ether is
    C-O bond because we know that ether
    can be prepared from alkyl halides by
    substitution with an alkoxide anion.

    C-O ether
    + +

    Target molecule : 2,4-D Synthons


    In above case we should certainly choose
    the anion of the phenol and some
    functionalised acetic acid molecule with a
    leaving group in the position as reagents
    equivalent to the synthons.
    Synthetic
    equivalents are real chemical compounds
    carrying out the function of a synthons.

    H
    -

    Synthons Synthetic equivalent


    +
    Cl
    GUIDELINES FOR CHOOSING
    DISCONNECTION
    GUIDELINE 1: Disconnection must
    correspond to the reverse of real and
    workable reactions.
    In case of herbicide
    2,3-D we chose to disconnect next to the
    oxygen atom because we know about the
    synthesis of ethers. We chose not to
    disconnect on the aryl side of oxygen atom
    because we know of no real and workable
    reaction corresponding to nucleophlic attack
    of an alcohol on an unactivated aromatic ring.
    Good choice of disconnection
    Because there is a real reverse
    reaction
    +
    +

    Bad choice of disconnection


    Because there is no real
    reaction +
    +

    -
    GUIDELINE 2: For compounds consisting
    of two parts joined by a heteroatom,
    disconnect next to the hetroatom.
    This guideline works
    for esters, ethers, amines, acetals, ketals,
    sulphides, and so on, because these
    compounds are often prepared by a
    substitution reaction.
    RETROSYNTHETIC ANALYSIS OF CHLORBENSIDE
    C-S sulphide
    -
    +

    synthon
    chlorobenside
    We can now suggest reagents (synthetic
    equivalents) corresponding to the synthons
    and can suggest a synthetic scheme for
    chlorobenside.
    - H + Base

    Cl

    Synthons Synthetic equivalent


    FUNCTIONAL GROUP
    INTERCONVERSION
    Function group interconversion (FGI) is the
    process
    of converting one functional group into
    another during retrosynthetic analysis. FGIs
    mostly involves oxidation, reductions and
    substitutions
    For
    example, in designing a synthesis of the
    local anasthetic benzocaine we know that
    esters are made from alcohol and acid so
    we can write a C-O disconnection.
    ANALYSIS 1:

    C-O ester
    OH
    + CH3 CH2 OH

    We should now like to disconnect –COOH or –


    NH2 from the aromatic ring but we do not
    know of any good reverse reactions
    corresponding to these disconnection.
    Aromatic acids can be made by the oxidation
    of methyl groups and amino group by
    reduction of nitro group.
    ANALYSIS 2:
    We are telling about the forward
    reaction
    we are going to do at this step
    CH3

    FGI reduction FGI oxidation

    NH2

    Disconnection of nitro group is rational


    because nitration of toluene occurs easily,
    and toluene is available
    ANALYSIS 3:

    This completes the retrosynthetic


    analysis
    THANK YOU

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