Phase transfer under alkaline conditions

The advantages of this method are clear the carbene is generated from the CCls anion in the organic phase, where there is a low concentration of water despite the presence of a separate aqueous phase. This means that the reaction of the carbene with the alkene is much more likely than hydrolysis. Sodium hydroxide can be used as the base in place of more expensive metal alkoxides because the aqueous phase has no detrimental effect on the reaction. 

Recent work has described the generation of difluorocarbenes from a mixture of bromoform and dibromodifluoromethane under basic condi- 

Recent work has shown that hydroxybenzophenones, which are more usually prepared by Friedel-Crafts chemistry, can be synthesized from phenols and a,a,a-trichlorotoluene by using aqueous sodium hydroxide and a phase transfer catalyst such as triethylbenzoylammonium chloride [22]. This method favours C-benzoylation over attack at the phenolic oxygen, and avoids the dealkylation, isomerisation and scrambling which are an inherent problem in the Friedel-Crafts method. 

Not all workers, however, are convinced of the validity of the accepted mechanisms for these types of reactions. Tan et al have studied a phase transfer catalysed Williamson ether synthesis by electrochemical methods including cyclic voltammetry [23], and came to the conclusion that 

This work flies in the face of traditional phase transfer theory, but may lead to new, more efficient, reaction systems. 

---

Chiral crown ethers such as 13 are suitable alternatives to the ammonium salts and not decomposed under alkaline conditions. They usually have higher catalyst turnover than the chiral ammonium salts, and the design of catalysts will be much easier. However, they are, in general, costly and difficult to prepare on large scale. Polyols (eg., (RR)-TADDOL14) also serve as phase transfer catalysts. 

Asymmetric a-hydroxylation of ketones 97 through phase transfer catalysis under alkaline conditions was realized by use of the Merck catalyst 7 (R=4-CF3, X=Br)[721 as well as the chiral azacrown ether 98[731 in conjunction with molecular oxygen, as shown in Scheme 30. The highest enantioselectivity of 79% ee was attained in the a-hydroxylation of the tetralone 100 by use of the Merck cata-... 

Sodium dithionite is well established [ 1 ] as a powerful reducing agent under alkaline conditions. Its redox potential is close to that of sodium borohydride [2] and, in several respects, there are advantages in the use of sodium dithionite as an alternative to the metal hydrides under phase-transfer catalytic conditions, particularly in the reduction of carbonyl compounds [3],... 

Saturated hydrocarbons can be chlorinated in moderate yields under mild conditions in a biphasic system consisting of alkaline hypochlorite solution and CH2CI2 containing Ni(Il) bis(saHcyHdene)ethylenediamine as chlorination catalyst and bexadecyltrimetbylammonium bromide as phase-transfer catalyst (166). 

PETP flakes produced from used soft drinks bottles were subjected to alkaline hydrolysis in aqueous sodium hydroxide. A phase transfer catalyst (trioctylmethylammonium bromide) was used to enable the depolymerisation reaction to take place at room temperature and under mild conditions. The effects of temperature, alkali concentration, PETP particle size, PETP concentration and catalyst to PETP ratio on the reaction kinetics were studied. The disodium terephthalate produced was treated with sulphuric to give terephthalic acid of high purity. A simple theoretical model was developed to describe the hydrolysis rate. 17 refs. 

Preparation of the donor 46 was started from 4,6-0-benzylidene protected thiomannoside 47 (Scheme 7.24). Alkylation with p-allyloxybenzyl chloride under phase transfer conditions78 was followed by 3-O-silylation and Pd(0)-mediated deallylation79 to give 48. The phenolic OH group was alkylated with ethyl 6-bromohexanoate and carboxylic acid, liberated by alkaline hydrolysis, was reacted with PEG monomethyl ether (MW -5000) under Mitsunobu conditions to afford 46. 

In many respects the apparently analogous reduction of nitroarenes with triruthenium dodecacarbonyl under basic phase-transfer conditions is superior to that of the iron carbonyl-mediated reductions. However, the difference in the dependence of the two processes on the concentration of the aqueous sodium hydroxide and the pressure of the carbon monoxide suggests that they may proceed by different mechanisms. Although the iron-based system is most effective under dilute alkaline conditions in the absence of carbon monoxide, the use of 5M sodium hydroxide is critical for the ruthenium-based system, which also requires an atmosphere of carbon monoxide [11]. The ruthenium-based reduction has been extended to the... 

In the presence of ruthenium trichloride, alkaline sodium hypochlorite is able to oxidize methylbenzenes to benzoic acids under phase-transfer conditions at room temperature. In a recent development, selective oxidation of xylenes to toluic acids has... 

Another important use of the susceptibility of phosphonium salts to undergo alkaline hydrolysis concerns their use as liquid-liquid phase-transfer catalysts. Phosphonium salts can be decomposed much more easily than ammonium salts, under alkaline conditions726-729, and they have to be used under much milder conditions [i.e. low temperature (< 25 °C) and moderate aqueous base concentration (< 15%)] in all cases reaction conditions should be used which prevent the extraction of OH - into the organic phase or minimize its reactivity730. 

If used under mild, alkaline conditions to prevent further oxidation of the 1,2-diol formed, KMnC>4 can be a selective oxidizing agent434,435 However, proper experimental conditions (extensive stirring in dilute solution,436 phase-transfer catalysis437 140), or other permanganate salts441 [Eq. (9.93)] are required to achieve high yields ... 

Aminocrotononitrile reacts with hydrogen sulfide in an alkaline medium under phase transfer catalysis conditions and gives mainly 4-thiapyranone (239) with 4-thiapyranthione (240) as a minor product. In... 

The use of a quaternary ammonium hydroxide as a phase transfer catalyst provides an efficient conversion of xanthene (174) to xanthone under mild conditions (77TL2117), while the use of permanganate under milder conditions than those shown in Scheme 9 enables flavenes such as (175) and (176) to be converted into flavones (77BCJ3298, 78BCJ1175). The phase transfer oxidation requires strongly alkaline conditions which may render it less suitable for the oxidation of flavenes and chromenes. Xanthene has also been converted into xanthone by means of permanganate or chromic acid. 

These cyclic aminomercurials are particularly prone to alkene formation and rearrangement during reduction. However, alkaline sodium borohydride under phase transfer conditions usually works well.2 9,2 ... 

The alkylation reaction of various alkali and alkaline-earth metal carbonates with alkyl halides R(CH2)nX (X = Cl, Br, I) is a primary synthetic procedure in organic chemistry for obtaining various symmetrical and unsymmetrical dialkyl carbonates under phase-transfer conditions in polar aprotic solvents [45]. Excellent yields may be obtained by running the reaction at 383 K in ionic liquids such as... 

Reduction of conjugated diunsaturated acids.3 a,/ y, 5-Diunsaturated acids are reduced by sodium dithionite in an alkaline medium (NaOH, NaHC03) to a mixture of (Z)- and (E)-/J,y-unsaturated acids (40 75% yield). A similar reduction of the diunsaturated esters is possible under phase-transfer conditions (Adogen 464, C6H6-HzO). 

Phase-transfer catalysed N-alkylation of diphenylphosphinic amide (I) is totally unsuitable in the case of easily hydrolysable organic halides, especially those containing additional functional groups (i.e. carbonyl or carboalkoxyl) which decompose readily in strongly alkaline medium. To circumvent the difficulty connected with simultaneous mono- and dialkylation of (I) under anhydrous conditions, N-(t-butyloxycarbonyl) diethyl phosphoroamidate (X), a doubly-protected ammonia derivative, was devised as a useful and superior substitute of phthalimide in the Gabriel-type synthesis of amines. 

Intramolecular Marschalk reactionAn intramolecular Marschalk reaction (9, 376) can be used to effect a synthesis of anthracyclinones from anthraquinones. Thus the a-hydroxy aldehyde 2, formed on saponification of the a-hydroxydichloride 1, on reduction of the quinone group cyclizes in the alkaline medium to the tetracyclic trans- and cw-diols (3 and 4) in about equal amounts. Cyclization under phase-transfer conditions results in improved yields and, more importantly, can alter the stereoselectivity. Triton B is the most effective catalyst for stereoselective cyclization to the desired natural trans-diol. 

---