Phase transfer synthesis

Hisamoto, H., Saito, T, Tokeshi, M., Hibara, a., Kitamori, T., Fast and high conversion phase-transfer synthesis exploiting the liquid-liquid inteface formed in a microchannel chip, Ghent. Commun. (2001) 2662-2663. 

Here we describe a phase-transfer synthesis as an example of a suitable microscale synthesis reaction, in which the large specific interfacial area and short molecular diffusion distance play important roles not only for effective main reaction, but also for avoiding an undesirable side reaction [50],... 

Herriot, A. Picker, D., The Phase-Transfer Synthesis of Sulfides and Dithioacetals. Synthesis... 

Table 5.8. Phase transfer synthesis of glycidic nitriles...

One interesting variant of the phase-transfer synthesis of chlorides involves the use of concentrated aqueous HCl as chloride reservoir. Water insoluble primary alcohols were stirred and heated with HCl in the presence of hexadecyltributylphosphonium bromide. The reactions were slow but ultimately yielded well [11]. The data are included in Table 9.1. 

Table 9.9. Phase transfer synthesis of cluster compounds [49]...

Alkyl thiocyanates react with a variety of nucleophiles to yield thioethers (see Sect. 13.4). A particularly clever and useful application of this reaction is the dialkylation of phenylacetonitrile with 1,2-dithiocyanatoethane. The product of this formal oxidation is the ethylenedithioketal of benzoyl cyanide (see Eq. 10.18) [30]. The phase transfer synthesis of the starting material from thiocyanate ion and ethylene bromide... 

Iron. - A mild phase transfer synthesis of [Fe2(M-CH2)(CO)0] is reported 27a his complex is cleaved by insertion of C0. 27b complex... 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Reaction of perfluoroaLkenes and hypochlorites has been shown to be a general synthesis of perfluoroepoxides (32) (eq. 7). This appears to be the method of choice for the preparation of epoxides from internal fluoroalkenes (38). Excellent yields of HFPO from hexafluoropropylene and sodium hypochlorite using phase-transfer conditions are claimed (34). 

Alkylation of protected glycine derivatives is one method of a-amino acid synthesis (75). Asymmetric synthesis of a D-cx-amino acid from a protected glycine derivative by using a phase-transfer catalyst derived from the cinchona alkaloids (8) has been reported (76). 

Pha.se-Tra.nsfer Ca.ta.lysts, Many quaternaries have been used as phase-transfer catalysts. A phase-transfer catalyst (PTC) increases the rate of reaction between reactants in different solvent phases. Usually, water is one phase and a water-iminiscible organic solvent is the other. An extensive amount has been pubHshed on the subject of phase-transfer catalysts (233). Both the industrial appHcations in commercial manufacturing processes (243) and their synthesis (244) have been reviewed. Common quaternaries employed as phase-transfer agents include benzyltriethylammonium chloride [56-37-17, tetrabutylammonium bromide [1643-19-2] tributylmethylammonium chloride [56375-79-2] and hexadecylpyridinium chloride [123-03-5]. 

The synthesis of optically active epoxy-1,4-naphthoquinones (69) using ben2ylquininium chloride as the chiral catalyst under phase-transfer conditions has been reported (67). 2-Meth5l-l,4-naphthoquinone (R = CH ) (31) yields 70% of levorotatory (37). 2-Cyclohexyl-l,4-naphthoquinone... 

W. P. Weber and G. W. Gokel, Phase-Transfer Catalysis in Organic Synthesis, Spriager-Vedag, Berlin, Germany, 1977. 

Soild-8quld phase transfer catalyst 2 (or aliphatic and arematic nudeophiftc substitution also synergistic effect with Cu in UHmann synthesis. 

Compound 1, 2,2-diniethyl-4-pentenal, has been prepared by the Claisen rearrangement route described above and by reaction of isobutyraldehyde with allyl chloride in the presence of aqueous sodium hydroxide and a phase-transfer catalyst. Both routes are applicable to the synthesis of a variety of substituted 4-pentenals. 

Phase transfer catalysis processes (Starks and Liotta, 1978 Starks, 1987) for the synthesis of many organic materials use less, or sometimes no, organic solvent may use less toxic solvent may allow use of less hazardous raw materials (for example, aqueous HCl instead of anhydrous HCl) and may operate at milder conditions. Some types of reactions where phase transfer catalysis has been applied include ... 

Tomoi and coworkers adopted a somewhat more direct approach in their synthesis of 16-crown-5 derivatives bearing a single alkenyl residue. They hoped to obtain precursors to polymers which could be used as phase transfer catalysts. In this approach I,I-bis-chloromethylethylene (a-chloromethallyl chloride) was allowed to react with the dianion of tetraethylene glycol (NaH/THF). By this method, methylene-16-crown-5 could be isolated in 66% yield after vacuum distillation. Ozonolysis led, in almost quantitative yield, to the formation of oxo-16-crown-5 as shown in Eq. (3.38). These authors prepared a number of other, closely related species by similar methods. 

Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

The synthesis of fluoroalkyl and chloroalkyl fluoromethyl ketones is achieved by oxidation of the corresponding alcohols by sodium dichromate and sulfunc acid in methylene chlonde in the presence of a phase transfer catalyst [49] (equation 45)... 

W. P. WF-BERandC. W. GOKEL, Phase Transfer Catalysis in Organic Synthesis, Vol. 4 of Reactivity and Structure, Springer-Verlag, 1977, 250 pp. C. M. Starks and C. Uotta, Phase Transfer Catalysis, Academic Press, New York, 1978, 365 pp. F. MontanaRI, D. Landini and F. Rolla, Topics in Current Chemistry 101, 149-201 (1982). E. V. Dehmlow and S. S. Dehmlow, Phase Transfer Catalysis (2nd edn.), VCH Publishers. London 1983, 386 pp. T. G. Southern, Polyhedron 8. 407-13 (1989). 

In addition, NaOMe, and NaNH2, have also been employed. Applieation of phase-transfer conditions with tetra-n-butylammonium iodide showed marked improvement for the epoxide formation. Furthermore, many complex substituted sulfur ylides have been synthesized and utilized. For instance, stabilized ylide 20 was prepared and treated with a-D-a/lo-pyranoside 19 to furnish a-D-cyclopropanyl-pyranoside 21. Other examples of substituted sulfur ylides include 22-25, among which aminosulfoxonium ylide 25, sometimes known as Johnson s ylide, belongs to another category. The aminosulfoxonium ylides possess the configurational stability and thermal stability not enjoyed by the sulfonium and sulfoxonium ylides, thereby are more suitable for asymmetric synthesis. 

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

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