Solid-liquid PTC

Although the use of phase-transfer catalysis (PTC) for manufacturing esters has the merits of a mild reaction condition and a relatively low cost [1], PTC has its limitations, such as the low reactivity of carboxylic ion by liquid-liquid PTC [2], a slow reaction rate by solid-liquid PTC, and the difflculty of reusing the catalyst by both techniques. 

Solid-liquid PTC conditions in which the nucleophilic salts (organic or mineral) are transferred from the solid state (as they are insoluble) to the organic phase by means of a phase-transfer agent. Most often the organic nucleophilic species can be formed by reaction of their conjugated acids with solid bases (sodium or potassium hydroxides, or potassium carbonate) (Scheme 5.1 path b). Another proposed mechanism suggests that interfacial reactions occur as a result of absorption of the liquid phase on the surface of the solid. 

PTC reactions are perfectly tailored for microwave activation, and combination of solid-liquid PTC and microwave irradiation gives the best results in this area [8] ... 

Similarly to classical PTC reaction conditions, under solid-liquid PTC conditions with use of microwaves the role of catalyst is very important. On several occasions it has been found that in the absence of a catalyst the reaction proceeds very slowly or not at all. The need to use a phase-transfer catalyst implies also the application of at least one liquid component (i.e. the electrophilic reagent or solvent). It has been shown [9] that ion-pair exchange between the catalyst and nucleophilic anions proceeds efficiently only in the presence of a liquid phase. During investigation of the formation of tetrabutylammonium benzoate from potassium benzoate and tetrabu-tylammonium bromide, and the thermal effects related to it under the action of microwave irradiation, it was shown that potassium benzoate did not absorb micro-waves significantly (Fig. 5.1, curves a and b). Even in the presence of tetrabutylammonium bromide (TBAB) the temperature increase for solid potassium benzoate... 

Numerous reactions in organic synthesis can be achieved under solid-liquid PTC and with microwave irradiation in the absence of solvent, generally under normal pressure in open vessels. Increased amounts of reactants can be used to ensure better compatibility between the in-depth penetrability of materials and the radiation wavelength. 

Catechol was reacted with /fmethallyl chloride under the action of MW and PTC conditions yields of 2-methallyloxyphenols varied from 59 to 68% under liquid-liquid conditions (Tab. 5.8), whereas no reaction was observed in a solid-liquid PTC procedure (Eq. 14) [25]. 

Condensation of salicylaldehyde and its derivatives with a variety of esters of chlo-roacetic acids in the presence of TBAB led to the synthesis of benzo[fo]furans by means of a solid-liquid PTC reaction under the action of microwave irradiation [33], This was a modification of one of the most popular routes to substituted benzo[fo]fu-... 

Under solid-liquid PTC conditions 5,5-diethylbarbituric acid was N,N-dialkylated in a good yield in the presence of a lipophilic ammonium salts and potassium carbonate when reaction mixtures were irradiated in a household microwave oven (Eq. 26). 

N-Substituted amides and lactams can be rapidly N-alkylated under solid-liquid PTC conditions by use of microwave irradiation. The reactions were performed simply by mixing an amide with 50% excess of an alkyl halide and a catalytic amount of TBAB. These mixtures were absorbed on a mixture of potassium carbonate and potassium hydroxide [41] and then irradiated in an open vessel in a domestic micro-wave oven for 55-150 s (Eq. 28). 

The starting reagents in Gabriel amine synthesis, N-alkylphthalimides, were obtained under the action of microwave irradiation in a solid-liquid PTC system. The reactions were conducted with high yield (50-90%) simply by mixing phthalimide... 

Rapid monoalkylations are achieved in good yield compared with classical methods. Of particular interest is the synthesis of ot-amino acids by alkylation of aldimines with microwave activation. Subsequent acidic hydrolysis of the alkylated imine provides leucine, serine, or phenylalanine in preparatively useful yields within 1-5 min [50], Alkylation of phenylacetonitrile was performed by solid-liquid PTC in 1-3 min under microwave irradiation (Eq. 36 and Tab. 5.14). The nitriles obtained can subsequently be quickly hydrolyzed in a microwave oven to yield the corresponding amides or acids [56]. 

Bromoacetals in basic media can be converted to cyclic ketene acetals (Eq. 51). These -eliminations, previously performed under solid-liquid PTC without solvent and with sonication [70], were further improved by microwave irradiation (Tab. 5.22) [71]. 

Solvent-free SNAr reactions under solid-liquid PTC conditions were realized by using methoxide or phenoxide as nucleophiles. The main results, and comparison with those from classical heating, are indicated in Tab. 5.24 for activated (e.g. 4-nitro-halobenzenes) or nonactivated (e.g. a-naphthyl halides) substrates [74]. 

Loupy and Soufiaoui described a comparative study of the reactivity of diphenylnitri-limine 200 with several dipolarophiles under microwave irradiation in the absence of solvent using a solid mineral support or phase-transfer catalysis (PTC) conditions (Scheme 9.62) [30b]. The results showed that the best yields of adducts were achieved upon impregnating KF-alumina with a mixture of the hydrazynoyl chloride 199 and the dipolarophile followed by irradiation of the mixture in a focused oven. Reaction of this mixture under solid-liquid PTC conditions with KF-Aliquat under microwaves afforded lower yields of cycloadducts, perhaps owing to the partial decomposition of Aliquat at the reaction temperature (140 °C). In all cases, worse yields were obtained by classical heating under comparable reaction conditions (time and temperature). 

The early, independent work of Starks, Markosa and Brandstrom from ca. 1965-1969, brought into focus with Starks classical paper in 1971, showed PTC to be potent and versatile synthetic tool.[1-4] Since that time, the well-documented investigations of PTC have been massive and vigorous.[5-7] In polymer chemistry PTC was effectively exploited first in anionic addition polymerization and more recently has been extended to condensation polymerization.[5,8-9] However, until a very few years ago, the use of solid-liquid PTC systems in polycondensation has for the most part escaped this intensive scrutiny. Consequently, some time ago we began a rather broad study into the use of solid-liquid PTC to effect polycondensations.[10]... 

We initiated our work by examining nucleophilic aromatic substitution, a somewhat difficult reaction to effect in other than activated aryl halides as substrates. It occurred to us that if polyhaloaromatics could be made to suffer disubstitution under mild solid-liquid PTC conditions, then they might be used as comonomers with a variety of bisnucliophiles to prepare halogenated polyaryl-ethers, sulfides, sulfone-ethers as well as other interesting polymers which are at present synthesized only with some difficulty. 

Our approach was to study structure reactivity relationships in a number of model reactions and, then, to proceed to the usually more difficult polymerizations using a variety of comonomer pairs. Secondly, we hoped to optimize the various, experimental solid-liquid PTC parameters such as nature and amount of catalyst, solvent, nature of the solid phase base, and the presence of trace water in the liquid organic phase. Finally, we wished to elucidate the mechanism of the PTC process and to probe the generality of solid-liquid PTC catalysis as a useful synthetic method for polycondensation. 

Effect of Solvent and Catalyst on Solid-liquid PTC Polymerization of HFB ... 

The presence of trace amounts of water in the organic phase is known to affect profoundly the rate of solid-liquid PTC processes. [11-13] Only recently has this problem been addressed by work in our laboratory as well as by Liotta and Sasson. Early in our polymerization studies we found that PTC polymerization did not occur in "bone dry" or "wet" solvents. Consequently, we undertook a... 

IL. Dilute solution viscosity measurements were done at 30 with the appropriate Ostwald-Fenske capillary viscometers. The water content of all organic solvents, used as the liquid phase in solid-liquid PTC runs was analyzed by potentiometric Karl Fischer titration using a Metrohm AG CH 9100 model automatic titrator. 

While the greatest percentage of PTC-aided anionic substitutions involve non-aromatic systems (7-10), a number of liquid-liquid and solid-liquid, PTC-aided SnAr reactions have been reported (32-38). These reports involve a variety of substrates [unactivated (32,33), slightly activated (M), activated (35-37), and transition metal complexed 32,38)1, nucleophiles OMe (32,38), CN ( ), SR (34) SCN (36), SO (36), OR (37)] and PTCs... 

Triazines (60) have been prepared by reaction of KOCN with an alkyl chloride, involving trimerization of alkyl isocyanate intermediates formed in solid-liquid PTC.109... 

Albanese, D. Landini, D. Penso, M. Regio-selective opening of epoxides to /1-ammo alcohols under solid-liquid PTC conditions. Tetrahedron 1997, 53, 47874790. 

The advantages of PTC reactions are moderate reaction conditions, practically no formation of by-products, a simple work-up procedure (the organic product is exclusively found in the organic phase), and the use of inexpensive solvents without a need for anhydrous reaction conditions. PTC reactions have been widely adopted, including in industrial processes, for substitution, displacement, condensation, oxidation and reduction, as well as polymerization reactions. The application of chiral ammonium salts such as A-(9-anthracenylmethyl)cinchonium and -cinchonidinium salts as PT catalysts even allows enantioselective alkylation reactions with ee values up to 80-90% see reference [883] for a review. Crown ethers, cryptands, and polyethylene glycol (PEG) dialkyl ethers have also been used as PT catalysts, particularly for solid-liquid PTC reactions cf. Eqs. (5-127) to (5-130) in Section 5.5.4. 

Benzylquininium chloride has been studied as a catalyst for the asymmetric Michael reaction. Reaction of amidoma-lonate (5) and chalcone (4) with catalytic base and a variety of chiral, nonracemic ammonium salts in the absence of solvent produced (6) in yields of 41-68% and 20-68% ee (eq 2). The quinine-derived salt (1) was of intermediate effectiveness (38% ee, 47% yield) when compared to ephedrine-based catalysts. Although (1) was not specifically tested with regard to solvation effects, it is suggested that increased aggregation of reactive species under solid-liquid PTC conditions leads to enhanced organization and selec-... 

Treatment of [Co(CO)4] under PT conditions with a mixture of alkyne and Mel (excess) in a CO atmosphere gives hydroxybut-2-enolides (eq. (12)) [148]. When benzyl bromide is used instead of Mel, the but-2-enolides are not formed due to the fast hydrolysis of the acylcobalt carbonyl intermediate [PhCH2COCo(CO)4] before the alkyne complex is formed. This obstacle has been overcome by carrying out the reaction in the absence of water, using solid/liquid PTC [149]. The direction of the PTC carbonylation of alkynes in the presence of Mel changes again when cobalt and ruthenium carbonyls are used simultaneously (1 1) [150]. In this case, y-ketoacids are obtained. 

The allylation of terminals alkynes catalyzed by Cu salts proceeds smoothly under solid/liquid PTC conditions [178]. More recently, it was shown that the allylation of alkynes can be effectively carried out under classical liquid/liquid PTC conditions in the presence of CuCl and quaternary ammonium salt [179]. 

Barry, J. Bram, G. Decodts, G. Loupy, A. Sansoulet, J., Easy and Efficient Anion Alkylations in Solid-Liquid PTC Conditions. Tetrahedron Lett. 1982, 23,5407. 

The alkylation of potassium benzoate with n-octyl bromide under classical solid-liquid PTC (crown ether, chloroform) leads to only 58 % of n-octyl ester after 40 h at 85 °C. Under solvent-free conditions (2% of Aliquat), yield is quasi-quantitative (95%) within 2 h at the same temperature [Eq. (47)] [81]. 

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