Solvent-free PTC

Dealkoxycarbonylation of activated esters occurs classically under drastic thermal conditions [90]. It constitutes a typical example of a very slow-reacting system (with a late TS along the reaction coordinates) and is therefore prone to a microwave effect. The rate determining step involves a nucleophilic attack by halide anion and requires anionic activation, which can be provided by solvent-free PTC conditions under the action of microwave irradiation [91]. The above results illustrate the difficult example of cyclic /1-ketoesters with a quaternary carbon atom in the a position relative to each carbonyl group (Eq. 36). 

Tab. 3.16 The Krapcho reaction under solvent-free PTC conditions.

Alkylation of several substituted benzoic acid salts with n-octyl bromide was performed under solvent-free PTC with excellent yields (95 %) within a very short reaction time [93] (2-7 min). Oil bath heating (A) led to yields equivalent to those produced under the action of microwave irradiation, which thus revealed only thermal effects in the range of temperature used (145-202 °C) (Eq. 39). 

A facile synthesis of a series of N-alkylpyrrolidino[60]fullerenes by solvent-free PTC under the action of microwaves has been described (Eq. 31). 

Microwave activation and solvent-free PTC have been shown to be of prime efficiency for the synthesis of new benzylidene cineole derivatives (UV sunscreens) by the Knoevenagel reaction. When performed classically by use of KOH in ethanol at room temperature for 12 h (Eqs. 43 and 44) the yield was 30%. This was improved to 90-94% within 2-6 min under PTC + MW conditions (Tabs 5.17 and 5.18) [27, 28],... 

Tab. 5.24 Solvent-free PTC S tgAr reactions under MW + PTC conditions (potassium salts). ...

One-pot syntheses of diaryl-a-tetralones by Michael condensation and subsequent Robinson annulation reactions of isophorone with chalcones were performed efficiently in a solvent-free PTC system under the action of MW irradiation. Compared with conventional heating substantial rate enhancements were observed, within very short reaction times, by use of microwaves (Eq. 59 and Tab. 5.31). They were far better than those achieved by the classical method (NaOEt in EtOH under reflux for 24 h 40-56%). 

Long-chain alkylating agents, poorly reactive, are almost inert under classical PTC conditions in the presence of solvents. Yet, they present a significant interest when reacted with some other molecules (e. g. detergents, liquid crystals, organic conductors, etc.) or as such for their lipophilicity. Under solvent-free PTC, they can react with good yields under rather mild conditions. 

As an example, phenols react with long-chain bromoalkanes under harsh conditions (refluxing DMF). In the case of p-hydroxybenzaldehyde, under liquid-liquid PTC, only a Cannizaro reaction occurred after one week. On the other hand, solvent-free PTC resulted in a quantitative yield in long chain ether within 5 h [Eq. (46)] [80]. 

The different solvent-free techniques have been compared during safrole iso safrole isomerization (Table 5). Solvent-free PTC requires by far the least drastic conditions and only a stoichiometric equivalent amount of base. The use of a very strong base (KOtBu) means that the catalyst can be removed and an identical result can be achieved by increasing the time from 5 min to 3 h at 80°C... 

Under solvent-free PTC conditions, catalytic amounts of base (K2CO3 or KOH) and of phase transfer agent (Aliquat) are sufficient, simulating high dilution conditions. Retro-Michael reaction can be consequently limited [Eq. 

This constitutes strong evidence that the MW specific effect is noticeably substrate dependent and increases when the reaction becomes increasingly difficult, as pointed out by Lewis et al. [ 142]. In particular, the almost impossible saponification of hindered and long-chain esters can be achieved easily under solvent-free PTC when coupled with MW. 

Anionic -elimination Ketene acetal synthesis by j8-elimination of haloacids from halogenated acetals under solvent-free PTC conditions under well controlled conditions using thermal activation (A), ultrasound (US), or microwave irradiation [152] (MW) has been described. Mechanistically, as the TS is more charge delocalized than the GS and the polarity is enhanced during the course of the reaction, a favorable microwave effect is expected, and is actually observed (Eqs. (65) and (66), Scheme 4.16). 

Solid-liquid solvent-free PTC was applied, with noticeable improvement and simplification compared with classical procedures, in a green chemistry context, for synthesis of some aromatic esters useful as cosmetic ingredients - 3-methylbutyl 4-methoxycinnamate, 2-ethylhexyl 4-methoxycinnamate, 2-ethylhexyl 4-(dimethylamino)benzoate, and 2-ethylhexyl salicylate, all well-known ultraviolet B sunscreen filters, 4-isopropylben2yl salicylate, a UV absorber and cutaneous anti-lipoperoxidant, the parabens propyl 4-hydroxybenzoate and butyl 4-hydroxyben-zoate (Eq. 7), and antimicrobial agents [16]. 

Cyclopropane derivatives can be obtained by reacting active methylene compounds and 1,2-dibromoethane using a solvent-free PTC + MW technique (Eq. 

Synthetic Applications of Phase-tranter Processes 311 Tab. 6.27. Solvent-free PTC SfjAr of pyridine halides. 

Synthesis of a series of N-alkylpyrrolidino[60]fullerenes (61a-e) was, nevertheless, achieved by use of a combination of microwave irradiation and PTC in the absence of solvent (Scheme 21.22) [65]. Solvent-free PTC has been successfully applied to a wide range of organic reactions and the technique is very useful when combined with microwave irradiation, especially for anionic reactions that proceed slowly, give low yields, or require harsh conditions. 

Cyclic ketene acetals can be generated from cyclic p-bromo acetals and potassium hydroxide (Eq. 35).The best results were obtained by using a combination of ultrasound irradiation and solvent-free PTC. jhis reaction occurs in the "dry" state in the presence of TBAB at room temperature. 

---