Increase Productivity increase yield reduce cycle time reduce or consolidate unit operations increase reactor volume efficiency Improve Environmental Performance eliminate, reduce or replace solvent reduce non-product output Increase Quality improve selectivity reduce variability Enhance Safety control exotherms use less hazardous raw materials Reduce Other Manufacturing Costs eliminate workup unit operations use alternate less expensive or easier to handle raw materials are you currently using NaOMe/OEt/t-butoxide, NaH, NaNH 2, LDA, water sensitive reactants, chlorinated hydrocarbon solvents, DMSO, DMF Fázis transzfer katalízis 1

Desired Reaction O-Alkylation (Etherification) N-Alkylation C-Alkylation & Chiral Alkylation S-Alkylation Dehydrohalogenation Esterification Displacement With Cyanide Hydroxide, Hydrolysis Fluoride Thiocyanate, Cyanate Iodide Sulfide, Sulfite Azide Nitrite, Nitrate Other Nucleophilic Aliphatic & Aromatic Substitution Oxidation Epoxidation & Chiral Epoxidation Michael Addition Aldol Condensation Wittig Darzens Condensation Carbene Reactions Thiophosphorylation Reduction Carbonylation HCl/HBr Reactions Transition Metal Co-Catalysis Any Reaction Above for Polymerization Any Reaction Above for Modifying Polymers 2

3 What is Phase-Transfer Catalysis? Phase-Transfer Catalysis is useful primarily for performing reaction between anions (and certain neutral molecules such as H 2 O 2 and transition metal complexes such as RhCl 3 ) and organic substrates. PTC is needed because many anions (in the form of their salts, such as NaCN) and neutral compounds are soluble in water and not in organic solvents, whereas the organic reactants are not usually soluble in water. The name phase-transfer catalysis does what it says...the catalyst acts as a shuttling agent by extracting the anion or neutral compound from the aqueous (or solid) phase into the organic reaction phase (or interfacial region) where the anion or neutral compound can freely react with the organic reactant already located in the organic phase. Reactivity is further enhanced, sometimes by orders of magnitude (!), because once the anion or neutral compound is in the organic phase, it has very little (if any) hydration or solvation associated with it, thereby greatly reducing the energy of activation. Since the catalyst is often a quaternary ammonium salt (e.g., tetrabutyl ammonium, [C 4 H 9 ] 4 N + ), also called the "quat" and symbolized by Q +, the ion pair Q + X - (X - being the anion to be reacted) is a much looser ion pair than say Na + X -. This looseness of the ion pair is a third key reason for enhanced reactivity, which will ultimately lead to increased productivity (reduced cycle time) in commercial processes. At the end of the reaction, an anionic leaving group is usually generated. This anionic leaving group is conveniently brought to the aqueous (or solid) phase by the shuttling catalyst, thus facilitating the separation of the waste material from the product. This mechanism is called the "extraction mechanism" of phase-transfer catalysis.

4 The extraction mechanism easily accounts for the benefits of PTC which include: achieving high reactivity (reactants are in the same phase with less hydration in a loose ion pair); extreme flexibility in choosing or eliminating solvent (a properly chosen quaternary ammonium catalyst can extract almost any anion into almost any organic medium, including into the product or into one of the organic reactants resulting in a solvent-free process); reducing the excess of water-sensitive reactants (such as phosgene, benzoyl chloride, esters and dimethyl sulfate since they are protected in the bulk organic phase from the aqueous phase by interfacial tension); higher selectivity (lower energy of activation allows reduction of reaction temperature and time); the use of inexpensive and less hazardous bases (hydroxide is easily transferred and activated in nearly all organic solvents) and many other benefits.

5 FT katalizátorok

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Amidok dehidratálása diklórkarbénnel fázistranszfer körülmények között: az amid laktim formája reagál Amidok dehidratálása tionil-kloriddal 7

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A carbene is a species that has a formally neutral carbon atom bearing two nonbonded valence electrons. A carbene has the following general structural formula:structural formula A carbene could exist in two spin states: singlet carbene and triplet carbene. In a singlet carbene, the two nonbonded valence electrons in the electron-deficient carbon are in the same orbital, i.e., they are a lone pair. In a triplet carbene, the two nonbonded valence electrons in the electron-deficient carbon are in different orbitals. Since a triplet carbene has unpaired electrons, it is, by definition, a radical.

10 Alkének

11 Simmons-Smith reakció

12 Singlet Diradicals Singlet diradical species behave as if they have both a Lewis base (HOMO) centre and a Lewis acid (LUMO) centre. For carbenes, nitrenes and oxenes these two centres occur at the same atom. Singlet carbene, CH2, has two electrons in a Lobe-HOMO Lewis base centre and a vacant p-orbital LUMO. The two centres react with alkenes in a concerted, single-step manner and so give rise to stereospecific products. Singlet diradicals undergo 1,1-addition reactions with cis-alkenes with retention of relative stereochemical configuration:

13 Triplet Diradicals Triplet Diradicals have two non-spin paired electrons which behave as a pair of radical (SOMO) centres. (A SOMO is a singly occupied molecular orbital and defined as half the HOMO of a free radical. It shows the difference of energies between orbitals.)free radical These two centres react with an alkene in a stepwise fashion. This means that molecular rotation can occur around the "single" bond between the reactions steps. The result is that triplet diradicals give stereo mixed addition products:

14 Generation of carbenes