Danielle L. Jacobs- Microwave Assisted Organic Synthesis

8/3/2019 Danielle L. Jacobs- Microwave Assisted Organic Synthesis

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Microwave AssistedOrganic Synthesis

Danielle L. Jacobs

Crimmins Group Meeting

10/11/06


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So how did those TV

dinners become sopopular?


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History

Randall & Booth (WWII)

Formed basis of radar transmitters

Raytheon Company (1946)

Commercially available in 1954 for $5,000

Industrial/domestic wavelength regulated

at 2.45 GHz

Initially used in industry for irradiating coal,drying, ceramic processing, etc


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History

Other applications limited as it wasperceived heating phenomenon arose

exclusively from w intrxns with water Used since late 1970s for inorganic rxns

Organic rxns in mid-1980s, but only

recently exploded Lack of controllability, reproducibility,

safety aspects


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Electromagnetic Spectrum

Electric field component

Responsible for dielectric heating

Dipolar polarization

Conduction

Magnetic field component


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Dipolar Polarization

Average Relaxation Time average time ittakes for a collection of molecules to

randomize after electric field is switchedoff

Debye Equation

= 4r3/kT r ~ molecular size

~ viscosity (intermolecular forces)


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Dipolar Polarization

Loss Tangent (Energy Dissipation Factor) a measure of the ability to absorb

microwave energy and convert it intothermal energy (heat)

Derived from Maxwells eqn

tan=/ = loss factor

= dielectric constant


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Conduction

Due to translational motion of electriccharges when an electric field is applied

Ions cause increased collision rate andconvert kinetic energy to heat

Tap water vs. distilled water


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Rate Enhancement

Arrhenius Equation

k=Ae-Ea/RT

Does not decrease rxn Ea Increases pre-exponential factorA

Thermodynamic rxns more affected than

kinetic rxns


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Thermodynamics vs. Kinetics

polar transition state:excellent formicrowave energy

transfer


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Thermodynamics vs. Kinetics

resonance-stabilizedintermediates oftenhave longer lifetimes


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Thermal Effects

More efficient energetic coupling of solventwith microwaves promotes higher rate of

temperature increase Inverted heat transfer, volumetric

Hot spots in monomode microwaves

Selective on properties of material(solvents, catalysts, reagents,intermediates, products, susceptors)


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Selective Solvent Effects

Biphasic systems

Ionic solvents

High BP, low VP, high thermal stability,environmentally friendly

Nucleation Limited Boiling Point (NLBP)


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Method Development

Open vessel vs. pressurized system

Solvent selection

Polar/ionic rapid rise in T, above BP

Non-polar behaves as heat sink

Solventless rxn mixture is absorbing

Time, temperature, power settings

Reflux, simultaneous cooling, orcontinuous flow options


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Microwaves in Industry

Pharmaceuticals

Combichem

Med chem

Process chemistry

Green chemistry

Solvent-free rxns

Solid-support

MORE


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The Contest


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Recent Applications of MAOS

MCROrganocatalysis

OlefinationRadical rxns

MetathesisReduction

RearrangementOxidation

Organometallic rxnsHeterocycles

(Trans)esterification(De)protectionCycloadditionCondensation

Nucleophilic substitutionAlkyl/aryl coupling

AlkylationN-acylation


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Heterocycles

Fresneda, P.M.; Molina, P.; Sanz, M.A.; Synlett2001, 218.

Coleman, C.M.; MacElroy, J.M.D.; Gallagher, J.F.; OShea, D.F. J. Combinatorial Chem.2002, 4, 87.

Nolt, M.B., et. al. Tetrahedron2006

, 62, 4698.


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Organometallic Reactions

Skoda, Foldes, R., et. al. Steroids, 2002, 67, 709.

Trost, B.M.; Andersen, N.G.; J. Am. Chem. Soc. 2002, 124, 14320.

Trost, B.M>; MeEachern, E.J.; Toste, F.D.; J. Am. Chem. Soc. 1998, 120, 12702.


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Rearrangements

Pelc, M.J.; Zakarian, A. Tetrahedron Lett. 2006, 47, 7519.

Pelc, M.J.; Zakarian, A. Org. Lett. 2005, 7, 1629.

Pelc, M.J. Thesis, Florida State University.


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Rearrangements

Craig, D.; Henry, G.D. Eur. J. Org. Chem. 2006, 3558.


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Cross Metathesis

Bargiggia, F.C.; Murray, W.V. J. Org. Chem. 2005, 70, 9636.


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What the Hell is Sparging?

Nosse, B.; Schall, A.; Jeong, W.B.; Reiser, O.Adv. Synth. Catal.2005, 347, 1869.


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Radical Initiation

Homolytic cleavage of weak bonds occurswithout initiators

Jessop, C.M.; Parsons, A.F.; Routledge, A.; Irvine, D.J. Eur. J. Org. Chem. 2006, 1547.

Hartung, J.; Daniel, K.; Gottwald, T.; Grob, A.; Schneiders, N. Org. Biomol. Chem. 2006, 4, 2313.


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Lead References

Lidstrm, P.; Tierney, J.P.; Wathey, B.; Westman, J.Tetrahedron2001, 57, 9225

Hayes, Brittany, L. Microwave Synthesis. Chemistry at theSpeed of Light. North Carolina: CEM Publishing, 2002.

Tierney, J.P., and P. Lidstrm, ed. Microwave AssistedOrganic Synthesis. Oxford: Blackwell Publishing Ltd, 2005.

de la Hoz, A.; Diaz-Ortiz, A.; Moreno, A. Chem. Soc. Rev.2005, 34, 164.

Danielle L. Jacobs- Microwave Assisted Organic Synthesis

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