Phase transfer method

A mixture of the azole (10 mmol), tetrabutylammonium bromide (1 mmol) and potassium hydroxide (20 mmol) are placed in an ultrasound bath for 2-3 h. A slight excess of p-fluoronitrobenzene (11 mmol) is then added, and the mixture 

Weak bases can assist the reaction. Naturally, the only useful W-acyl substituents of use in lithiation sequences are the acetals (e.g. dialkoxymethyl), which can be made quite readily by treating the imidazole with a trialkyl orthoformate with p-toluenesulfonic acid as a catalyst. The groups are easily removed again, but have the drawback of also being unstable under dilithiation conditions [25, 55]. 

A solution of p-toluic acid (6.8g, 50mmol) in THF (80ml) and 1,1 -carbonyldiimidazole (7.2g, SOmmol) in THF (80ml) is allowed to stand 

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The present method utilizes dichlorocarbene generated by the phase-transfer method of Makosza4 and Starks.5 The submitters have routinely realized yields of pure distilled isocyanides in excess of 40%.6 With less sterically hindered primary amines a 1 1 ratio of amine to chloroform gives satisfactory results. Furthermore, by modifying the procedure, methyl and ethyl isocyanides may be prepared directly from the corresponding aqueous amine solutions and bromoform.7 These results are summarized in Table I. 

Prepared by the phase-transfer method using chloroform and aqueous sodium hydroxide with the corresponding amines.8 6 Bromoform substituted for chloroform for ease of fractionation.7... 

After separation of excess amalgam a solution of MXj is added. Reaction is rapid and the desired product can be separated from the Na halide or NaCN produced. If the separation of the amalgam is incomplete it is possible for Hg to be incorporated into the product (see 8.3.3.4). To avoid this, other methods of preparing carbonyl anions can be used, such as reaction with NaBH4, Na-K and other reducing agents ", or phase-transfer methods. ... 

Extraction of protein from aqueous solution by surfactant-containing lipophilic organic solvent (phase transfer method, or equivalently, w/o-ME-based liquid-liquid extracting, LEE). 

The phase transfer method of protein solubihzation is fundamentally different from the other two methods. In this method, there are two bulk phases (aqueous and organic) which are brought to equihbrium. Under certain conditions, the protein molecules are transferred from the aqueous phase to the surfactant-containing organic phase. Unhke the dry-addition and injection methods, it is difficult to obtain a value for the maximum solubihzation using the phase-transfer method. Moreover, since this method is mainly used for protein extraction, it is desirable to use aqueous phase protein concentrations consistent with those in a typical fermentation broth. For the phase-transfer method, pH of the aqueous phase, the size and isoelectric point of the protein, and the surfactant type were shown to have a significant effect on protein solubilization [145]. 

An alternative to the injection method for importing enzymes into a microemulsion is the phase transfer method. In this method, a layer of an aqueous enzyme solution is located under a mixture of surfactant and oil. Upon gentle shaking, the enzyme is transferred into the reverse micelles of the hydrocarbon phase. Finally, the excess of water is removed and the hydrophobic substrates can be added. The main advantage of this method is that it ensures thermodynamically stable micro emulsions with maximum water concentrations. However, the method is very time consuming. The method is often applied in order to purify, concentrate or renaturate enzymes in the reverse micellar extraction process [54-58]. 

The elimination procedure described below is merely offered as an alternative, which may be chosen when no mill is available for powdering KOH (indispensable in the phase--transfer method) or when no high-boiling petroleum ether is available. 

Vinylacetylene from l,4-Dichloro-2-butene (phase-transfer method)... 

The phase transfer method has been also applied successfully, by Kim and Szarek,44 to unreactive trans-/ -diols and cis-/ -diols (8). 

This asymmetric phase-transfer method has been applied to enantio-selective Robinson annelation as shown in Scheme 14 (41). First, alkylation of a 1-indanone derivative with the Wichtetie reagent as a methyl vinyl ketone equivalent in the presence of p-CF3BCNB gives the S-alkylation product in 92% ee and 99% yield. With 1 -(p-trifluoro-methylbenzyl)cinchonidinium bromide, a pseudo-enantiomeric diaste-reomer of p-CF3BCNB, as catalyst, the -alkylation product is obtained in 78% ee and 99% yield. These products are readily convertible to the... 

The final step, incorporation of ALmethyl-D-leutine, can be carried out as follows. D-Leucine was protected as its benzyloxycarbonyl derivative, and methylation was carried out by the phase-transfer method described above for tyrosine. BOP-promoted coupling between Z,Me-D-Leu-OH and the macrocycle, followed by deprotection, gives didemnin A (60). 

The phase-transfer method has also been used for the synthesis of aryl, benzyl, vinyl and heterocyclic carboxylic acids by carbonylation of the corresponding halides (equation 105).476... 

The phase-transfer method has also been employed for the carbonylation of benzylic halides to carboxylic acids.477 The palladium(O) complexes [Pd(PPh3)4] (103), [Pd(diphos)2] (104) and [Pd(DBA)2] (105 DBA = dibenzylideneacetone) were used as catalysts. With (103) and (104) the carboxylic acid was the major product. Complex (105) gave little or none of the acid, the toluene and bibenzyl derivatives corresponding to the benzyl halide used being formed. Benzyl esters of the carboxylic acid were sometimes present as minor products. The reaction has been adapted to provide a new synthesis of anthranilic acid derivatives (equation 106).478 Tri-n-butylamine was used to neutralize the HBr formed. 

The formation of acylnaphthalenes 225 occurs under mild conditions (catalysis by sodium rm-butoxide or with the use of the phase-transfer method and TEBA as catalyst), and it affords high yields (60-90%). In this connection, it is surprising to recall the opinion about the incapability of 2-benzopyrylium salts to take part in recyclization reactions with compounds possessing active methylene groups, with secondary amines, or with sulfur or phosphorus nucleophiles (71CB2984). 

The power of this phase-transfer method is also emphasized by the economics of the process. It was reported that the cost of producing the desired (S) enantiomer on the basis of the asymmetric organocatalytic alkylation route using an amount of catalyst below 10 mol% was significantly lower than the cost of producing the isomer by a resolution process [50],... 

Various nucleophiles substitute cyclic sulfamidates such as 521 at C(5) at room temperature and provide good yields of 522, e.g., <1996S259, 1999J(P1)1421, 1999TL3831, 2002TL1915>. The introduction of the N-substitutent to make compounds like 521 is best achieved via a base-catalyzed phase-transfer method or using the Mitsunobu protocol <2002JOC5164>. 

One of the oldest techniques for overcoming these problems is the use of biphasic water/organic solvent systems using phase-transfer methods. In 1951, Jarrouse found that the reaction of water-soluble sodium cyanide with water-insoluble, but organic solvent-soluble 1-chlorooctane is dramatically enhanced by adding a catalytic amount of tetra-n-butylammonium chloride [878], This technique was further developed by Makosza et al. [879], Starks et al. [880], and others, and has become known as liquid-liquid phase-transfer catalysis (PTC) for reviews, see references [656-658, 879-882], The mechanism of this method is shown in Fig. 5-18 for the nucleophilic displacement reaction of a haloalkane with sodium cyanide in the presence of a quaternary ammonium chloride as FT catalyst. 

The asymmetric epoxidation of electron-deficient olefins, particularly a,/3-enones, including the use of chiral metal hydroperoxides, asymmetric phase-transfer methods, polyamino acid catalysts, and the chiral dioxiranes, has been reviewed <2000CC1215>. 

Dihydropyridines may be prevented from undergoing further reduction by carrying out reductions in aprotic solvents or in protic systems at high pH. Phase transfer methods have also been used to remove the dihydro adducts from the reactive medium prior to further reduction. An elegant solution to the problem of overreduction was developed by Fry reduction is carried out in the presence of cyanide ion, which traps the dihydropyridine system as 2-cyano-l,2,3,6-tetrahydropyridine (57 Scheme 13). The addition of alkoxide re-forms the dihydropyridine (58). Separation of 1,4-dihydropyridines from mix-... 

The scope of this process is evident from extensive studies which have shown that the dihalocarbene can be generated from most of the usual precursors by using the phase transfer method . The reactivity of dihalocarbenes " and carbenoids " towards acetylenes has also been reported. 

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