Makosza catalyst

In the mid-1960s a series of papers by Makosza and Serafinowa (1965, 1966) appeared under the common title Reactions of Organic Anions , in which the catalytic alkylation of phenylacetonitrile and its derivatives carried out in the presence of concentrated NaOH and the catalyst triethylbenzylammonium chloride (TEBA) was described. This was the beginning of phase-transfer catalysis (PTC), and since then thousands of papers haven been published on the subject. 

Reactions performed under two-phase conditions are further complicated by the partitioning of the reactants and catalyst over the two phases. In the case of quaternary ammonium phase-transfer catalysis, the mechanistic aspects have received a great deal of attention (Brandstrom, 1977 Makosza, 1975 Starks and Owens, 1973). In contrast, the mechanism of crown ether-type phase-transfer catalysis has hardly been investigated at all, despite its... 

For synthetic purposes, crown ethers have been used frequently as phase-transfer catalysts under conditions where the sodium or potassium hydroxide is present as a concentrated aqueous solution. Various anions of C—H acids have been generated this way (Makosza and Ludwikow, 1974). The use of such conditions for the generation of carbenes will be dicussed in a separate section. 

Several variations of Makosza s procedure have been recorded using different catalysts. Generally, because of the need for the slow release of the dichlorocarbene in the presence of the reactive substrate, the weaker catalysts are preferred. There seems, however, to be some advantage in the use of multisite ammonium salts, e.g. 2-benzylidine-Ar,Ar,MA,.A,Ar -hexaethylpropane- 1,3-diammonium dichloride, PhCH=C(CH2NEt3)22+ 2CE, although yields and rate of reaction are not significantly better than those of Makosza s procedure [6, 7]. 

Because of the differential partitioning of hydroxide and phenoxide anions into organic solvents by quaternary ammonium cations, the catalysts generally have little effect on the Reimer-Tiemann reaction of phenols with dihalocarbenes [15]. Cetyltrimethylammonium bromide has been used in the two-phase dichloromethyl-ation of polysubstituted phenols (Scheme 7.21, Table 7.10) under Makosza s conditions [16,17] ring expansion of the reaction products provides an effective route to tropones. The rate of the reaction is enhanced by ultrasonic radiation [16]. 

Other classic examples illustrating the use of quaternary salts as phase transfer catalysts were published by Makosza(2), and by Brandstrom(3). Subsequent development of crown ethers(4-7) and crvptands(7-8) as phase transfer catalysts gave PTC an entirely new dimension since now the inorganic reagent, as sodium cyanide in the above equation, need no longer be dissolved in water but can be used... 

Phase transfer catalytic processes (1-3) have been the subject of intensive study in many laboratories throughout the world since its potential was recognized almost simultaneously and independently by Starks ( ) and Makosza (. The principles outlined by Starks in 1971 ( ) have generally stood the test of time even though many compounds besides quaternary oniurn salts have been utilized as phase transfer catalysts (1-3). 

The first catalysts utilized in phase transfer processes were quaternary onium salts. In particular, benzyltriethylammonium chloride was favored by Makosza (7 ) whereas Starks utilized the more thermally stable phosphonium salts (6,8). In either case, the catalytic process worked in the same way the ammonium or phosphonium cation exchanged for the cation associated with the nucleophilic reagent salt. The new reagent, Q+Nu , dissolved in the organic phase and effected substitution. 

Catalyst-mediated decomposition of diazo compounds in the presence of C=S compounds has found application for the preparation of thiiranes in homogeneous systems (68,110,111). Recently, a convenient procedure for the preparation of geminal dichlorothiiranes from nonenolizable thioketones and chloroform under Makosza conditions was reported (112). Another approach to 2,2-dihalogenated thiiranes (e.g., 2,2-difluoro derivatives) involves the thermolysis of Seyferth reagents in the presence of thioketones (113,114a). Nucleophilic dimethoxycarbene was shown to add smoothly to adamantanethione to provide a unique approach to a thiiranone (5, 5 )-dimethylacetal (114b). 

Makosza and co-workers have reported the preparation of epoxides from a-halo carbanions and ketones, according to the Darzens reaction, under PT conditions, using TEBA72,73 or dibenzo-18-crown-6.74 The ratio of isomers depends on the reaction conditions.75,76 Asymmetric induction has been reported in the Darzens reaction using chiral catalysts.77,78 The use of several chloro carbanions as well as K2C03 and Na2C03 in the solid state has also been studied. 

Since asymmetric phase-transfer catalysts normally contain highly lipophilic chiral organic frameworks, and are reluctant to enter the aqueous phase, the Makosza interfacial mechanism seems plausible. 

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. 

Several quaternary ammonium compounds are used in organic chemistry as phase-transfer catalysts. The mechanism of the catalytic process can be represented by a combination of phase-transfer and ion-exchange equilibria. In the case of substitution reactions in two-phase systems, the negatively charged nucleophile is extracted by the positive ammonium ion from the aqueous phase into the organic phase where substitution takes place (Makosza and rafin, 1965, Makosza, 1969, Dockx, 1973). 

SoHd-liguid phase-transfer catalysis. Crown ethers have commonly been used as catalysts for reactions between a solid-liquid interface, and quaternary ammonium and phosphonium salts have been used only as catalysts for reactions in two-phase liquid liquid reactions. However, several laboratories have reported that the latter catalysts are also satisfactory for two-phase solid liquid reactions. Thus dichlorocarbene can be generated from chloroform and solid sodium hydroxide under catalysis from benzyltriethylammonium chloride in yields comparable to those of the classical Makosza method. Another example of this type of catalysis is the oxidation of terminal and internal alkynes by solid potassium permanganate in CH2CI2 with Adogen 464 as catalyst. Aliquat 336 has been found to be as satisfactory as a crown ether for certain displacement reactions with NaOAc, KSCN, KNOa, and KF in CH3CN or CHaCla. ... 

An elegant and effective method developed during the last twenty five years is the use of phase-transfer agents in catalytic amounts (the origin of this term is attributed to Starks 1971 see also Makosza, 1975 Brandstrdm, 1977). Any substance that can ion-pair with the anion of a nucleophile in the aqueous or solid phase (e.g., quaternary ammonium salts) or complex with its cationic half (e.g., crown ethers), thus extracting the nucleophile into the immiscible organic phase and then activating it for a reaction to occur there, can function as a phase-transfer (PT) catalyst. 

Not only does the solvent affect the reaction rate, but it also determines the reaction mechanism. In Starks extraction mechanism of PTC, most reacting compound transfers to the bulk phase. However, reaction may occur at the interface of the two phases. For example hexachlorocyclotriphosphazene has been reported to react very slowly with 2,2,2-trifluoroethanol in an alkaline solution of NaOH/C HjCl two-phase system in the absence of phase-transfer catalyst.Since sodium 2,2,2-trifluoroe anoxide is not soluble in chlorobenzene, the process probably proceeds at the interface region of the system. Similar is the reaction of benzylation of isobutyraldehyde in the presence of tetra-n-butylammonium iodide in an alkaline solution of NaOH/toluene, which is a two-phase system. Makosza interfacial mechanism was employed to rationalize the experimental results. The main reason is that the ammonium salt of the nucleophilic reagent is not soluble in toluene. 

Chloroform added dropwise at room temp, to a stirred mixture of N-methyl-aniline, aq. 50%-NaOH, benzyltriethylammonium chloride, and, optionally, methylene chloride, and stirring continued 1-2 hrs. -> N-formyl-N-methylaniline. Y 76%. F. e. s. J. Grafe, I. Frohlidi, and M. Muhlstadt, Z. Chem. 14, 434 (1974) s. a. M. Makosza and A. Kacprowicz, Rocz. Chem. 49, 1627 (1975) (Eng) C. A. 84, 43265 N-alkylation with alkyl halides, ibid. 49, 1203 (Eng) C. A. 84, 30793 cf. R. Brehme, Synthesis 1976, 113 with tetrabutylammonium hydrogen sulfate as phase transfer catalyst, indole derivs., cf. A. Barco et al., Synthesis 1976, 124. 

The Makosza interfacial mechanism begins with the formation of a metal carbanion species at the interface between the organic and aqueous phases in the absence of the phase-transfer catalyst. Extraction of this species from the interface to the organic phase then takes place, mediated by the phase-transfer catalyst (Figure 14). ... 

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