Phase transfer catalysis condensation

Industrial examples of phase-transfer catalysis are numerous and growing rapidly they include polymerisa tion, substitution, condensation, and oxidation reactions. The processing advantages, besides the acceleration of the reaction, include mild reaction conditions, relatively simple process flow diagrams, and flexibiHty in the choice of solvents. 

A recent literature report described a green procedure for the condensation of arylacetonitriles with cyclic ketones using phase-transfer catalysis. This process was applied to the synthesis of venlafaxine, which was realized in overall 30% yield in two steps from commercially available 14. The condensation step was run in aqueous sodium hydroxide in the presence of tetrabutylammonium sulfate, to provide quantitative yield of intermediate 15. Hydrogenation in a formalin-methanol mixture provided the final product venlafaxine (1) in 30% overall yield. This protocol did not necessitate intermediate purification steps, making it attractive from the commercial standpoint. 

A series of 3-alkyl- and 3-aryl-7/7-furo[3,2- ]-l-benzopyran-7-ones 78 (linear furocoumarins) was synthesized and evaluated for their photochemical and nonphotochemical crosslink formation with DNA as well as for their spectro-photometric and fluorescent properties, lipophilicity, and ability to photobleach A, A -dimethyl-/)-nitrosoaniline (RNO) after irradiation with UVA light <2002AP187>. The synthesis of the linear furocoumarins (Scheme 10) was a modification of a previously published method in which 7-hydroxy-2//-l-benzopyran-2-ones 76 were converted into / -ketoethers 77 by alkylation with haloketones under phase-transfer catalysis conditions. Base-catalyzed intramolecular condensation and subsequent acidification gave the corresponding 78. A molecular complex between each one of these fluorescent furocoumarins and DNA was observed, but only compounds with a 3-Me or 3-Ph group showed UVA irradiation-induced crosslink formation. 

HCA121). 3-Acetyl-4-hydroxy-l,5,5-trimethyl-2-pyrrolone 39a gives no acetylated products with either benzoyl chloride or benzoic anhydride, or acetic anhydride. By contrast phase-transfer catalysis (K2C03/CHC13 r.t.) affords a condensation product, formed from two molecules, 39a. This product does not bear a benzoyl group (87TH2). 

Reactions of carbanions, anions of weak organic acids (e.g., indole or carbazole), and dihalocarbenes may be carried out in liquid-liquid systems, in which concentrated aqueous sodium hydroxide is the aqueous phase. The term phase transfer catalysis is mechanistically incorrect these are often referred to as catalytic two-phase systems. Numerous reactions of carbanions including alkylation, nitroarylation, addition, the Darzens condensation, cyclopropanation, and also a variety of reactions of dihalocarbenes are conveniently carried out in this way. 

Compound 98 was condensed with o-aminothiophenol, 2-aminoethanol, or cystamine in refluxing diphenyl ether through an intermolecular cyclization with the elimination of two molecules of water to give the polyfused derivatives 101-103, respectively. Also, the reactions of 98 with dimethylthiomethylenemalononitrile in boiling dimethylforma-mide (DMF) were studied. The dimethylthiomethylenemalononitrile was prepared via the reaction of malononitrile with CS2 with 2 equiv of methyl iodide in a one-pot reaction using liquid-liquid phase-transfer catalysis (PTC) technique (NaOH/dioxane/tetrabutylammonium bromide (TBAB)). The product of this reaction was identified as 8-cyano-9-imino-7-methylthio-6-oxo-3-phenyl-5,6,8,9-tetrahydro-77/-pyrano[3,2-/][l,2,4]-triazolo[3,4-A][l,3,4]thia-diazepine 104 (Scheme 10). 

Whilst simple alkylations of enolates and Michael additions have been successfully catalyzed by phase-transfer catalysts, aldol-type processes have proved more problematic. This difficulty is due largely o the reversible nature of the aldol reaction, resulting in the formation of a thermodynamically more stable aldol product rather than the kinetically favored product. However, by trapping the initial aldol product as soon as it is formed, asymmetric aldol-type reactions can be carried out under phase-transfer catalysis. This is the basis of the Darzens condensation (Scheme 8.2), in which the phase-transfer catalyst first induces the deprotonation of an a-halo... 

Condensation of dibromomethane with the 1,2,4-triazepine 194 in phase-transfer catalysis conditions provides efficient and facile access to the biheterocyclic triazepine 42 with high regioselectivity (Equation 19) <1997TL2087>. 

Solid-liquid solvent-free phase transfer catalysis (PTC) is specific for anionic reactions including numerous alkylations, eliminations and anionic additions. The coupling of PTC conditions and microwave irradiation was applied to numerous alkylations, eliminations, anionic condensations, and... 

Intermolecular condensation with the formation of two C-O bonds is a viable approach to the benzo-annelated dioxocines (cf. 1996CHEC-II(9)527). Treatment of catechol with a,a -xylene dichloride afforded dihydrodi-benzo[, /][l,4]dioxocine 6 (an oil) in excellent yield (Scheme 19) <1995JOC8410>. Similarly, catechol reacted with l,2,4,5-tetrakis(bromomethyl)benzene to form the dibenzodioxocine 182 (m.p. 87-89 °C) in moderate yield <2001H(54)849, 2001T8667>. The dibromide 182 was further treated with phenanthrenequinone under reductive conditions to afford 9,13,18,22-tetraoxa-9,10,12,13,18,19,21,22-octahydrobenzo-9, 10 -phenanthro[i / ]benzo[l,2- 4,5- ]dicyclooctene 151 <2001T8667>. Catechol reacted with dibromoethane under phase-transfer catalysis conditions to form tetrahydro-l,6-benzodioxocine 183 in high yield <2001SC1>. 

Under phase-transfer catalysis (NaOll/TEBAC/CH2Cl2) condensation of diethyl bromomalonate with diethyl l-(methoxycarbonyl)vinylphosphonate leads to the cyclopropanation product, diethyl 2,2-/ zi(ethoxycarbonyl)-l-(melhoxycarbonyl)cyclopropylphosphonate, in 65% yicld. ... 

Examples of phase transfer catalysis include hydrolysis, condensation, oxidation, and polymerization ". There are many industrial applications. 

Although the reaction mechanism is not at the moment fully clarified, some points seem to be well established the radical character of the reaction and the contemporary need of an anion activator as PEG is (maybe the function of the anion activator is to increase the strength of the base as they do in Phase-Transfer Catalysis) (14). In place of PEG other anion activators may be used, as the condensation compounds between ethylene oxide and propylene oxide such latter polymers, being viscous liquids, offer some advantage in particular applications such as the decontamination of surfaces. 

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