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My Discussion falls under the following Headings:-

Introduction

The Main Synthesis

Reaction Conditions For Formylation

Reduction of (Z)--Cinnamaldehyde

Synthesis Of (Z)--fluoroconiferin

Conclusion

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Introduction:-

In the past five years, there has been a increased interest on Fluoro OrganicCompounds in pharmaceutical companies

Introduction of one Fluorine atom in a strategic position often leads to theanalogue of Natural Compounds

Among all Mono fluorinated compounds, 2-fluoropropenal and2-fluoropropenol got much importance

2-Fluoropropenals are key intermediates for synthesis of more complexstructures

2-Fluoropropenol is also the key structure for several biologically activecompounds

In this synthesis , they used the same Fluoro compounds for the synthesis of(Z)--Fluoroconiferin, a strong inhibitor of Lignin Polymerase

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Main Synthesis:-

In this Synthesis, they mainly reported the Stereo convergent Formylation of

(E/Z)--bromo--fluoro-Styrene with Carbon monoxide and Sodium fomatecatalyzed by the Palladium.

This will leads to the formation of (Z)--Fluoro cinnamaldehyde in good yields.

The reaction is further extended the reaction. They found that

(Z)--Fluoro cinnamaldehyde is reduced to corresponding(Z)--Fluorocinnamic alcohol by in presence of Sodium borohydrade(NaBH4)

They also reported the synthesis of (Z)--Fluoroconiferin by doing the reactionon functionalized substrates.

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The reactions for the synthesis are as follows:-

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Mechanism of Formylation:-

Firstly, the Pd Catalyst is added to the substrate oxidatively

Then, the insertion of CO occurs

Then, the exchange of Bromide by Formate anion

The expulsion of Carbon dioxide leads to the palladium hydridespecies

The transfer of hydride ion leading to the aldehyde.

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1H NMR Spectrum of (Z)--Fluorocinnamaldehyde:-

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1H NMR Spectrum of (Z)--Fluorocinnamic alcohol:-

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Reaction Conditions For Formylation:-

In order to get the desired compound that is (Z)-- Fluorocinnamaldehyde in pure form

several parameters are examined. They are:-

1. Nature Of Solvent

2. Number of Sodium formate Equivalents

3. Carbon monoxide Pressure

4. Temperature

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Nature Of Solvent:-

The Nature of solvent plays a very important role in the reaction to get ourdesired product

Firstly, they tried with the apolar solvents like Acetonitrile and THF. It has givenonly the reduced product(Biproduct)

Secondly, they tried with DMSO. Here also they got only the reduced product andthere is no desired product

Finally, they got the desired product that is (Z)--Fluorocinnamaldehyde withDimethyl formamide(DMF)

But, the formation of the desired product is also depends on other parameters also.

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Number of Formate Equivalents:-

In this synthesis, they used two amounts of Sodium formate equivalents

Firstly, they used 0.5 equivalents of Sodium formate . The usage of thisamount leads to the formation of the reduction biproduct((E)--Fluoro Styrene)

Secondly, they tried with the one equivalents of sodium formate.It results inthe formation of desired product?((Z)--Fluorocinnamaldehyde)

And no reaction occurred when used in excess.

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Carbon monoxide Pressure:-

Carbon monoxide pressure is playing a very important role in this reactioncompared to other parameters.

In this reaction they used high Carbon monoxide pressure and it increased the yieldof aldehyde and also caused the sharp increase in rate of reaction

It also allowed the decrease in temperature from 100 to 80 oC and time also reducedfrom 48h to 18h

At this pressure, no (E)--Fluorocinnamaldehyde is detected and the percentage ofour desired product (Z)--Fluorocinnamaldehyde is higher.

This results suggests that the (E)--Fluorocinnamaldehyde formed from the(Z)--bromo--fluoro-styrene is isomerized to (Z)--Fluorocinnamaldehyde

So, as the (E)-isomer isomerises to our desired (Z)-isomer, the combination of 800 Cand high pressure(40 bar) allow us to isolate pure (Z)- Fluorocinnamaldehyde in 78%

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All these reaction conditions that I discussed is shown in the Table below

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Reduction of (Z)--Fluorocinnamaldehyde to (Z)--Fluorocinnamic alcohol:-

The (Z)- -Fluorocinnamaldehyde is reduced in the presence of Sodium borohydrade in

Cold Methanol at -100C and leads to the formation of corresponding

(Z)--Fluorocinnamic alcohol in good yield(74-93%) without the saturation of doubleBond. The reaction is shown as below

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Synthesis of (Z)--Fluoroconiferin:-

The same method what is used above is used in the synthesis of

(Z)--FluoroconiferinVarious steps involve in this synthesis are explained as follows:-

Vanillin is first O-glycosylated by reaction with 1-bromo-2,34,6-tetraacetyl--D-glucopyranoside in biphasic condition

Here, tris-2-(2-Methoxy-ethoxy-ethyl)-amine(TDA) used as thephase transfer catalyst

The corresponding -bromo- -fluoro olefine is obtained from theWittig-Burton reaction

Formylation done is with CO, HCOONa and Pd under the conditionsused above

It leads to the formation of pure(Z)--fluoroaldehyde which is furtherreduced to alcohol by NaBH4 into alcohol.

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Finally, the deprotection of Acetyl groups are done by Sodium methanoate. It results

in the formation of (Z)--fluoroconiferin. The whole synthesis is shown below

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1H NMR Spectrum of (Z)--Fluoroconiferin:-

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Mass Spectrum of Formylation:-

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